Management

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

of the human proteome. Nature.

2014;**509**(7502):575-581

of Rab8 activation in zebrafish

2018;**8**(1):2211

photoreceptor outer segment formation and maintenance. Scientific Reports.

[44] Wang L, Lee K, Malonis R, Sanchez I, Dynlacht BD. Tethering of an E3 ligase by PCM1 regulates the abundance of centrosomal KIAA0586/Talpid3 and promotes ciliogenesis. eLife. 2016;**5**

[45] Stephen LA, Tawamie H, Davis GM, Tebbe L, Nurnberg P, Nurnberg G, et al. TALPID3 controls centrosome and cell polarity and the human ortholog KIAA0586 is mutated in Joubert syndrome (JBTS23). eLife. 2015;**4**

[46] Malicdan MC, Vilboux T, Stephen J, Maglic D, Mian L, Konzman D, et al. Mutations in human homologue of chicken talpid3 gene (KIAA0586) cause a hybrid ciliopathy with overlapping features of Jeune and Joubert

syndromes. Journal of Medical Genetics.

[47] Alby C, Piquand K, Huber C, Megarbane A, Ichkou A, Legendre M,

[48] Bachmann-Gagescu R, Phelps IG, Dempsey JC, Sharma VA, Ishak GE, Boyle EA, et al. KIAA0586 is mutated in Joubert syndrome. Human Mutation.

[49] Fleming LR, Doherty DA, Parisi MA, Glass IA, Bryant J, Fischer R, et al. Prospective evaluation of kidney disease in Joubert syndrome. Clinical Journal of the American Society of Nephrology:

CJASN. 2017;**12**(12):1962-1973

Nirujogi RS, Manda SS,

[50] Kim M-S, Pinto SM, Getnet D,

Chaerkady R, et al. A draft map

et al. Mutations in KIAA0586 cause lethal ciliopathies ranging from a hydrolethalus phenotype to short-rib polydactyly syndrome. American Journal of Human Genetics.

2015;**52**(12):830-839

2015;**97**(2):311-318

2015;**36**(9):831-835

**50**

**53**

**Chapter 5**

**Abstract**

acupuncture

**1. Introduction**

Advances in Treatment of

options for children with nocturnal enuresis.

Nocturnal Enuresis in Children

Nocturnal enuresis is a condition with complex etiology affecting plenty of children and families. Even though multifarious clinical trials and studies have been designed and completed, some inconclusive results on nocturnal enuresis confuse clinicians. This article aims to provide useful information for clinicians by summarizing the existing evidence on nocturnal enuresis and discussing the effectiveness and safety of different treatments. Nocturnal enuresis mainly results from the disorders related to central nervous system, which may cause nocturnal polyuria, nighttime bladder capacity decline, arousal disorder, and various accompanying diseases. We discussed the efficacy and safety of different treatments for monosymptomatic nocturnal enuresis, including standard therapies, simple behavioral interventions, complex behavioral interventions, alarm therapy, desmopressin and other drugs, biofeedback therapy, electrical stimulation, acupuncture, Chinese herbal medicine, massage, and so on. Alarm is still the most effective single therapy with lower relapse rate. Desmopressin has efficacy mainly in children with nocturnal polyuria. Children with detrusor overactivity or decreasing functional bladder capacity can choose anticholinergics. Additionally, tricyclic drugs, biofeedback therapy, electrical stimulation, acupuncture, massage, and so on are therapeutic

**Keywords:** nocturnal enuresis, alarm, desmopressin, behavioral interventions,

It is defined as an intermittent involuntary micturition during sleep in children over 5 years of age with at least two episodes per week and duration of more than 3 months [1]. Basically, NE is divided into non-monosymptomatic nocturnal enuresis (NMNE) and monosymptomatic nocturnal enuresis (MNE) according to whether there are daytime lower urinary tract symptoms. On the other hand, it is also classified into primary nocturnal enuresis (PNE) and secondary nocturnal enuresis (SNE) according to whether or not the duration of dry days is less than 6 months [1]. Secondary NE requires clinicians to identify and evaluate the diseases which NE is secondary to and treat them first. In PNE, NMNE usually means that children have more complex bladder dysfunction or other potential pathology and need to be referred to a specialist for further diagnosis and treatment. Although some children with MNE can be self-healing and the prevalence gradually decrease with age [2],

Nocturnal enuresis (NE) is a common disease that pediatricians often encounter.

*Bingying Zhou, Jianxin Lu, Peiqi Shi and Yifang An*

#### **Chapter 5**

## Advances in Treatment of Nocturnal Enuresis in Children

*Bingying Zhou, Jianxin Lu, Peiqi Shi and Yifang An*

#### **Abstract**

Nocturnal enuresis is a condition with complex etiology affecting plenty of children and families. Even though multifarious clinical trials and studies have been designed and completed, some inconclusive results on nocturnal enuresis confuse clinicians. This article aims to provide useful information for clinicians by summarizing the existing evidence on nocturnal enuresis and discussing the effectiveness and safety of different treatments. Nocturnal enuresis mainly results from the disorders related to central nervous system, which may cause nocturnal polyuria, nighttime bladder capacity decline, arousal disorder, and various accompanying diseases. We discussed the efficacy and safety of different treatments for monosymptomatic nocturnal enuresis, including standard therapies, simple behavioral interventions, complex behavioral interventions, alarm therapy, desmopressin and other drugs, biofeedback therapy, electrical stimulation, acupuncture, Chinese herbal medicine, massage, and so on. Alarm is still the most effective single therapy with lower relapse rate. Desmopressin has efficacy mainly in children with nocturnal polyuria. Children with detrusor overactivity or decreasing functional bladder capacity can choose anticholinergics. Additionally, tricyclic drugs, biofeedback therapy, electrical stimulation, acupuncture, massage, and so on are therapeutic options for children with nocturnal enuresis.

**Keywords:** nocturnal enuresis, alarm, desmopressin, behavioral interventions, acupuncture

#### **1. Introduction**

Nocturnal enuresis (NE) is a common disease that pediatricians often encounter. It is defined as an intermittent involuntary micturition during sleep in children over 5 years of age with at least two episodes per week and duration of more than 3 months [1]. Basically, NE is divided into non-monosymptomatic nocturnal enuresis (NMNE) and monosymptomatic nocturnal enuresis (MNE) according to whether there are daytime lower urinary tract symptoms. On the other hand, it is also classified into primary nocturnal enuresis (PNE) and secondary nocturnal enuresis (SNE) according to whether or not the duration of dry days is less than 6 months [1]. Secondary NE requires clinicians to identify and evaluate the diseases which NE is secondary to and treat them first. In PNE, NMNE usually means that children have more complex bladder dysfunction or other potential pathology and need to be referred to a specialist for further diagnosis and treatment. Although some children with MNE can be self-healing and the prevalence gradually decrease with age [2],

most treatments for NE cannot achieve high cure rates and may cause high relapse rates. This may result from the complexity and uncertainty of the etiology of NE and the use of inappropriate treatment.

#### **2. Epidemiology**

According to Jain et al.'s review, the prevalence of MNE varies from 3.8 to 18.9% in different countries [2]. The risk factors related to NE reported in different studies include constipation, positive family history, obstructive respiratory disorder, deep sleep, corporal punishment at school, urinary tract infection, etc. [3–6]. However, the effect of each factor on NE varies from study to study, and no universal conclusion is drawn. The results from different studies may be contradictory. For example, a few researches reported that the prevalence of NE was significantly higher in boys than the one in girls [3, 7], while other studies draw the opposite conclusion that girls' prevalence is higher [8]. The potential reasons for the contradiction of results in different studies performed in different countries may be related to the difference in diagnostic criteria followed by each survey, sample size, sampling method, questionnaire design, and cultural background in different regions. According to Wen's survey about NE in Chinese children, the overall prevalence was 4.07%, which is much lower than counterparts in other countries [9]. In it, Dr. Wen reported that Chinese parents would wake their children to void once they found children's dysphoria due to the fullness of the bladder. Besides, he also found that Chinese parents were more likely to withdraw the diaper for their children as early as possible, which is believed to be helpful for the children to build normal urination habits. Similar to the mechanism of alarm therapy, these actions may have a positive effect to promote the establishment of reflex between bladder filling feeling and urination. It is important to analyze epidemiological data, which may help us to understand the importance of the children and their parents' behavior and other complex physiological, pathological, and social psychological elements involved in the prevalence of NE.

#### **3. Clinical diagnosis and treatment algorithm**

There are a few diagnosis and treatment algorithms of NE proposed by the International Children's Continence Society (ICCS), the International Continence Society (ICS), and some other literatures with similarities and differences. In this part, the algorithm of the ICCS's practical consensus guideline is introduced and modified.

NE has many possible causes: genetic factors, renal physiological factors, deficiency of antidiuretic hormone (ADH, vasopressin) leading to nocturnal polyuria, bladder dysfunction, arousal disorder, maturation delay, circadian rhythm disorder, etc. Moreover, many associated diseases such as obstructive sleep-disordered breathing, constipation, fecal incontinence, attention deficit disorder (ADD) and attention deficit hyperactivity disorder (ADHD), obesity, psychological problems, etc. can also be seen in children with NE. These associated diseases should be identified in the clinical evaluation and be treated first. For children without those conditions, the increase in nocturnal urine production and nighttime bladder capacity reduction are the two main prototypes. To provide an outline in the diagnosis and management of NE, we build an algorithm after summarizing available guidelines. **Figure 1** is the clinical diagnosis and treatment algorithm adapted from the guideline of Walle et al [10]:

**55**

**Figure 1.**

*Nocturnal enuresis algorithm (modified from Walle, 2012).*

*Advances in Treatment of Nocturnal Enuresis in Children*

2.Voiding diary (bladder diary) is not necessary.

whether to take alarm or desmopressin [11].

1.Clinical management tool is a medical history and symptoms collection form

3.After MNE is diagnosed, the 2012 guideline recommends directly the alarm and desmopressin treatment options. John Michael's review in 2014 recommends 6 weeks of urotherapy first and then evaluating the child to decide

4.EBC: expected bladder capacity, calculated as {30 + (age in years × 30)} in

5.MVV: maximum voided volume, the largest urine volume of 24 h (see part

*DOI: http://dx.doi.org/10.5772/intechopen.89106*

(see [10]).

milliliters.

bladder diary for details).

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

and the use of inappropriate treatment.

**2. Epidemiology**

most treatments for NE cannot achieve high cure rates and may cause high relapse rates. This may result from the complexity and uncertainty of the etiology of NE

According to Jain et al.'s review, the prevalence of MNE varies from 3.8 to 18.9% in different countries [2]. The risk factors related to NE reported in different studies include constipation, positive family history, obstructive respiratory disorder, deep sleep, corporal punishment at school, urinary tract infection, etc. [3–6]. However, the effect of each factor on NE varies from study to study, and no universal conclusion is drawn. The results from different studies may be contradictory. For example, a few researches reported that the prevalence of NE was significantly higher in boys than the one in girls [3, 7], while other studies draw the opposite conclusion that girls' prevalence is higher [8]. The potential reasons for the contradiction of results in different studies performed in different countries may be related to the difference in diagnostic criteria followed by each survey, sample size, sampling method, questionnaire design, and cultural background in different regions. According to Wen's survey about NE in Chinese children, the overall prevalence was 4.07%, which is much lower than counterparts in other countries [9]. In it, Dr. Wen reported that Chinese parents would wake their children to void once they found children's dysphoria due to the fullness of the bladder. Besides, he also found that Chinese parents were more likely to withdraw the diaper for their children as early as possible, which is believed to be helpful for the children to build normal urination habits. Similar to the mechanism of alarm therapy, these actions may have a positive effect to promote the establishment of reflex between bladder filling feeling and urination. It is important to analyze epidemiological data, which may help us to understand the importance of the children and their parents' behavior and other complex physiological, pathologi-

cal, and social psychological elements involved in the prevalence of NE.

There are a few diagnosis and treatment algorithms of NE proposed by the International Children's Continence Society (ICCS), the International Continence Society (ICS), and some other literatures with similarities and differences. In this part, the algorithm of the ICCS's practical consensus guideline is introduced and

NE has many possible causes: genetic factors, renal physiological factors, deficiency of antidiuretic hormone (ADH, vasopressin) leading to nocturnal polyuria, bladder dysfunction, arousal disorder, maturation delay, circadian rhythm disorder, etc. Moreover, many associated diseases such as obstructive sleep-disordered breathing, constipation, fecal incontinence, attention deficit disorder (ADD) and attention deficit hyperactivity disorder (ADHD), obesity, psychological problems, etc. can also be seen in children with NE. These associated diseases should be identified in the clinical evaluation and be treated first. For children without those conditions, the increase in nocturnal urine production and nighttime bladder capacity reduction are the two main prototypes. To provide an outline in the diagnosis and management of NE, we build an algorithm after summarizing available guidelines. **Figure 1** is the clinical diagnosis and treatment algorithm adapted from

**3. Clinical diagnosis and treatment algorithm**

**54**

the guideline of Walle et al [10]:

modified.


**Figure 1.** *Nocturnal enuresis algorithm (modified from Walle, 2012).*

### **4. Treatment**

#### **4.1 Urotherapy**

According to the 2006 ICCS's standardized terminology of lower urinary tract (LUT) function, urotherapy is defined as a nonsurgical and nonpharmacological treatment for LUT dysfunction [1]. It includes standard therapy which means the therapy is noninterventional and has specific interventions.

#### *4.1.1 Standard therapy*

The standard therapy usually has these components as below:


**57**

*1*

*2*

**Table 1.**

*stream interruption exercises.*

*Categories of behavioral interventions.*

*Advances in Treatment of Nocturnal Enuresis in Children*

to assess the presence of nocturnal polyuria (NP) through nighttime diary. It is also helpful to distinguish NMNE through finding out daytime polyuria, stress urinary incontinence, urgency urinary incontinence, etc. *A daytime diary* should include at least fluid intake time, urination time, fluid intake volume, urination volume, and the occurrence of urinary incontinence and exclude the first urination after getting up in the morning. The recording time should be at least 3–4 consecutive days. Children attending school can choose to record two consecutive weekends [10]. In daytime diary, the most important thing that requires clinicians' attention is the largest urinated volume which can indicate the child's bladder capacity. It can be determined if the bladder capacity is reduced or increased when the maximum voided volume is <65% or >130% expected bladder capacity (EBC's calculation formula is shown in **Figure 1**). *The nighttime diary* should include at least urination time (if the child gets up to the toilet), urination volume, diaper weight overnight, first urination volume after getting up in the morning, dry night or not (there is any enuresis or not), and whether there is bowel movement that day. The recording time should be at least seven consecutive nights [10]. What the nighttime diary can tell the clinicians is the child's amount of urine produced at night by adding first urination after getting up in the morning, the nighttime diaper weight, and nocturnal urination volume to the toilet. If the total nighttime urine output exceeds 130% EBC, it is determined as nighttime polyuria (NP). Through analyzing individual BD, children with MNE can be classified into one of the four subtypes as shown in **Figure 1**. Then the corresponding treatment could be determined. In addition, by calculating a child's body surface area, we can find whether the

, which means the child has polyuria; by observing a

Lifting or waking the children at night to urinate1

Full-spectrum home training (FSHT)

child's water taking, we can know if the child has polydipsia which is considered as a predictor of diabetes or kidney disease. It is worth noting that children with

Specific interventions comprise behavioral modification and nonbehavioral strategies including pelvic muscle floor training, biofeedback, electrical stimulation, etc. [1]. And the behavioral interventions can also be divided into simple and complex strategies based on whether it is a single action or they are composite

> Bladder training2 Fluid restriction Cleanliness training

Arousal therapy

*Lifting and waking therapy includes lifting with or without password and waking randomly or to a certain time.*

*Bladder training includes retention control training, pelvic floor muscle training, sphincter control exercises, and* 

these conditions are not suitable to take desmopressin.

Simple behavioral Interventions Reward systems

Complex behavioral interventions Dry bed training (DBT)

*DOI: http://dx.doi.org/10.5772/intechopen.89106*

24-h urine volume >2 L/m2

*4.1.2 Specific interventions*

interventions [16] (**Table 1**).

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

therapy is noninterventional and has specific interventions.

The standard therapy usually has these components as below:

According to the 2006 ICCS's standardized terminology of lower urinary tract (LUT) function, urotherapy is defined as a nonsurgical and nonpharmacological treatment for LUT dysfunction [1]. It includes standard therapy which means the

1.Health education. Health education refers to providing parents basic information about normal LUT function and the causes, risk factors, different treatments, and their implementation of MNE [1]. The clinicians should emphasize that the condition is common and can be healed by itself and that parents should have a positive attitude instead of thinking enuresis as a shame because this helps children to establish their motivation for active participation and reduce damage to their self-esteem, which is the key to treatment [12].

2.Lifestyle advice. Develop healthy drinking and eating habits: avoid foods or beverages that have a diuretic effect, such as theophylline or caffeine; eat early in the evening, with less oil and less salt; and no more water or food and fruit rich in fluid at least 2 h before going to bed. These all avoid excessive nighttime fluids in body which may lead to overmuch urine production during the night. However, for children with MNE, fluid restriction may have a risk of reducing bladder capacity resulting in a decrease in the ratio of bladder capacity to nocturnal urine output, and so nocturnal enuresis increases [13]. Therefore, adequate fluid intake during the day is important, especially during the morning and early afternoon hours [14]. It is also good for cultivating the child's feeling of bladder fullness. Moreover, a research indicates that holding exercises can increase the maximum voided volume of children with MNE, so it is better not to be active after dinner [15].

3.Developing regular voiding and bowel habits. As the ICCS recommended, children should develop a good habit of regular urination during the day and schedule to urinate before going to bed and in the early morning after waking up. The daily routine of micturition should be comprised of once in the morning, at least twice during school hours, and once each after school, at dinner, and before going to bed, with totally less than seven urinations during daytime [14]. Besides, parents should instruct the child to use a comfortable voiding posture to relax the pelvic floor muscles—and that means sitting on the toilet safely with the bottom and feet supported. Constipation is a common concomitant disease in children with NE, especially with NMNE. It is recommended to eat more foods rich in dietary fiber and develop regular bowel movements every day, best after breakfast. Based on current evidence,

medication can be used to soften children's stools if necessary [14].

4.Voiding diary or bladder diary (VD or BD). According to the 2012 ICCS's practical consensus guidelines for MNE's management [10], BD is recommended to assess the children's voiding habit, especially for the families in which parents are unclear about children's voiding history. The most important function of BD is to evaluate the bladder capacity of children through daytime diary and

**4. Treatment**

**4.1 Urotherapy**

*4.1.1 Standard therapy*

**56**

to assess the presence of nocturnal polyuria (NP) through nighttime diary. It is also helpful to distinguish NMNE through finding out daytime polyuria, stress urinary incontinence, urgency urinary incontinence, etc. *A daytime diary* should include at least fluid intake time, urination time, fluid intake volume, urination volume, and the occurrence of urinary incontinence and exclude the first urination after getting up in the morning. The recording time should be at least 3–4 consecutive days. Children attending school can choose to record two consecutive weekends [10]. In daytime diary, the most important thing that requires clinicians' attention is the largest urinated volume which can indicate the child's bladder capacity. It can be determined if the bladder capacity is reduced or increased when the maximum voided volume is <65% or >130% expected bladder capacity (EBC's calculation formula is shown in **Figure 1**). *The nighttime diary* should include at least urination time (if the child gets up to the toilet), urination volume, diaper weight overnight, first urination volume after getting up in the morning, dry night or not (there is any enuresis or not), and whether there is bowel movement that day. The recording time should be at least seven consecutive nights [10]. What the nighttime diary can tell the clinicians is the child's amount of urine produced at night by adding first urination after getting up in the morning, the nighttime diaper weight, and nocturnal urination volume to the toilet. If the total nighttime urine output exceeds 130% EBC, it is determined as nighttime polyuria (NP). Through analyzing individual BD, children with MNE can be classified into one of the four subtypes as shown in **Figure 1**. Then the corresponding treatment could be determined. In addition, by calculating a child's body surface area, we can find whether the 24-h urine volume >2 L/m2 , which means the child has polyuria; by observing a child's water taking, we can know if the child has polydipsia which is considered as a predictor of diabetes or kidney disease. It is worth noting that children with these conditions are not suitable to take desmopressin.

#### *4.1.2 Specific interventions*

Specific interventions comprise behavioral modification and nonbehavioral strategies including pelvic muscle floor training, biofeedback, electrical stimulation, etc. [1]. And the behavioral interventions can also be divided into simple and complex strategies based on whether it is a single action or they are composite interventions [16] (**Table 1**).


*1 Lifting and waking therapy includes lifting with or without password and waking randomly or to a certain time. 2 Bladder training includes retention control training, pelvic floor muscle training, sphincter control exercises, and stream interruption exercises.*

#### **Table 1.**

*Categories of behavioral interventions.*

#### *4.1.2.1 Simple behavioral interventions*

Most of the simple behavioral interventions were initially presented in some early literatures, because the effects of first-line treatment on NE had not yet been determined at the time. They are often used in clinical treatment, but the efficacy is controversial since it lacks high-quality evidence. A systematic review about the efficacy and safety of simple behavioral interventions for NE has been published in the Cochrane Library. Unfortunately, only limited evidence is available. For most interventions only a single clinical trial was included, and therefore the data cannot be combined for meta-analysis except for the comparison between bladder training and alarm [16]. Furthermore, some other important limitations about the clinical trials were discussed in this review: for children with NE included in the trials, MNE and NMNE were not further distinguished; most trials had methodological deficiencies, and more than half of the trials reporting continuous outcomes did not report SDs; the trials' sample size was small, risk of bias was high, and the confidence interval was too wide; since there is a lack of long-term follow-up after the end of treatment, no data were available to assess the long-term efficacy of the interventions [16]. The following is a summary of this review's conclusion which needs to be cautiously referenced.

In the simple behavioral interventions referring to reward systems, lifting or waking the children, bladder training, and fluid restriction (*cleanliness training was not reviewed*), though all of them were more effective statistically than the control group, none of them had a better effect than others at the end of the treatment. When compared with alarm or different drugs, they were usually less effective except for bladder training which has no significant difference with drugs [16]. In terms of safety, adverse events were not reported in the included trials.

Bladder training is a behavioral therapy aiming to increase bladder capacity and strengthen the control of bladder in children. According to the review, bladder training seemed to be superior to the nonactive movements group in gaining less mean wet nights at the end of the treatment. However, there was no difference in the number of children who did not achieve 14 dry nights [16]. Another prospective trial further revealed that the basic bladder training's effects mostly were pronounced after the third month of treatment for the MNE children who did not receive any previous treatment. Therefore, for children who are not strongly willing to accept behavioral interventions, early administration of alarm or desmopressin is necessary [17]. But it seems to have good efficacy in children with NMNE [18].

Lifting without password is a controversial intervention because it allows the children to urinate while asleep, but it is useless to reduce the occurrence of nocturnal enuresis [19]. Being consistent with the conclusions of this review, a study also showed that the lifting without password group had a significantly higher proportion in the number of dry children than the control group and was even superior to lifting with password group and rewards group. In terms of long-term effect, both lifting groups had more dry children than the two other groups during 3 years follow-up [20].

#### *4.1.2.2 Complex behavioral interventions*

Dry bed training (DBT) is the oldest complex behavioral interventions with a multicomponent package of nighttime waking schedule, cleanliness training, reinforcement techniques, and other interventions. It has different versions and a few adapted versions with some components removed [21]. Full-spectrum home training (FSHT) is a combination with alarm, cleanliness training, and retention

**59**

*1*

**Table 2.**

*Advances in Treatment of Nocturnal Enuresis in Children*

control training in the daytime. To maximize the effect, the FSHT needs to be overlearned (giving extra fluids at bedtime after successfully becoming dry). Specific implementation steps of DBT and FSHT have been described by Brown and Glazener [22, 23]. In a Cochrane review of NE, complex behavioral interventions were compared with control, alarm, and other complex behavioral interventions. Moreover, complex behavioral interventions removing alarm were compared with control, alarm, and complex behavioral interventions supplemented by alarm. The conclusions were that DBT or FSHT was better than control in efficacy and relapse rate and marginally superior to alarm alone. Either complex behavioral interventions removing alarm or control intervention was inferior to alarm alone or complex behavioral interventions supplemented by alarm. There is no evidence for the comparison between complex behavioral interventions removing alarm and control. Additionally, adverse events were not described by the trials [23]. Unfortunately, the included studies in the systematic review have some limitations including small scale, small quantity, and poor quality. Besides, it has to be mentioned that the interventions are heavy burdens

Alarm and reward system are the components of arousal therapy/training, which was reported to have a high efficacy and low relapse rate in an early literature [24]. However, they have not been recommended by the guideline [10] because

Biofeedback therapy and electrical stimulation therapy were originally used to treat voiding dysfunction, and now they have been tried to treat refractory MNE or PNE with a reported good efficacy. Dr. Hoekx and his colleagues prospectively evaluated the effect of bladder biofeedback in 21 boys and 3 girls (mean age 10.4 years). After treatment 17/24 patients showed good response that means they achieved totally dry. During the 60-month follow-up, 4 patients were lost, 15 were dry at night, and 4 continued bed-wetting. The proportion of children with small bladder capacity in responders is much less than the one in non-responders [26]. In a randomized clinical trial published in 2015, 54 children with PNE were included and randomly divided into interferential (IF) electrical stimulation group and control group. A responding rate was reported as 55.5 and 22% in the IF and control group at the 1-year follow-up (P = 0.01), respectively. In terms of the mean number of dry nights per week and the mean improvement score, the IF group was superior compared to control group. Additionally, no adverse events were reported [27]. In another trial, children with refractory MNE were randomly assigned to intra-anal biofeedback with behavioral therapy, electrical stimulation with behavioral therapy, and pelvic floor muscle training groups. The trial stated a total efficacy of three groups in the outcomes and that intra-anal ES group was superior to BF training group. But in these three outcomes, the method to assess nighttime bladder capacity with morning first urine volume is not accurate [28]. In short, there is no adequate clinical evidence to determine the

there is not enough clinical evidence, which is similar to FSHT [25].

therapeutic effectiveness of these NE treatments (**Table 2**).

*Including bladder biofeedback and intra-anal biofeedback*

*Categories of nonbehavioral interventions.*

Nonbehavioral interventions Biofeedback (BF)1

Electrical stimulation (ES)

*DOI: http://dx.doi.org/10.5772/intechopen.89106*

on families.

*4.1.2.3 Nonbehavioral interventions*

#### *Advances in Treatment of Nocturnal Enuresis in Children DOI: http://dx.doi.org/10.5772/intechopen.89106*

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

Most of the simple behavioral interventions were initially presented in some early literatures, because the effects of first-line treatment on NE had not yet been determined at the time. They are often used in clinical treatment, but the efficacy is controversial since it lacks high-quality evidence. A systematic review about the efficacy and safety of simple behavioral interventions for NE has been published in the Cochrane Library. Unfortunately, only limited evidence is available. For most interventions only a single clinical trial was included, and therefore the data cannot be combined for meta-analysis except for the comparison between bladder training and alarm [16]. Furthermore, some other important limitations about the clinical trials were discussed in this review: for children with NE included in the trials, MNE and NMNE were not further distinguished; most trials had methodological deficiencies, and more than half of the trials reporting continuous outcomes did not report SDs; the trials' sample size was small, risk of bias was high, and the confidence interval was too wide; since there is a lack of long-term follow-up after the end of treatment, no data were available to assess the long-term efficacy of the interventions [16]. The following is a summary of this review's conclusion which

In the simple behavioral interventions referring to reward systems, lifting or waking the children, bladder training, and fluid restriction (*cleanliness training was not reviewed*), though all of them were more effective statistically than the control group, none of them had a better effect than others at the end of the treatment. When compared with alarm or different drugs, they were usually less effective except for bladder training which has no significant difference with drugs [16]. In

Bladder training is a behavioral therapy aiming to increase bladder capacity and strengthen the control of bladder in children. According to the review, bladder training seemed to be superior to the nonactive movements group in gaining less mean wet nights at the end of the treatment. However, there was no difference in the number of children who did not achieve 14 dry nights [16]. Another prospective trial further revealed that the basic bladder training's effects mostly were pronounced after the third month of treatment for the MNE children who did not receive any previous treatment. Therefore, for children who are not strongly willing to accept behavioral interventions, early administration of alarm or desmopressin is necessary [17]. But it seems to have good efficacy in children

Lifting without password is a controversial intervention because it allows the children to urinate while asleep, but it is useless to reduce the occurrence of nocturnal enuresis [19]. Being consistent with the conclusions of this review, a study also showed that the lifting without password group had a significantly higher proportion in the number of dry children than the control group and was even superior to lifting with password group and rewards group. In terms of long-term effect, both lifting groups had more dry children than the two other groups during 3 years

Dry bed training (DBT) is the oldest complex behavioral interventions with a multicomponent package of nighttime waking schedule, cleanliness training, reinforcement techniques, and other interventions. It has different versions and a few adapted versions with some components removed [21]. Full-spectrum home training (FSHT) is a combination with alarm, cleanliness training, and retention

terms of safety, adverse events were not reported in the included trials.

*4.1.2.1 Simple behavioral interventions*

needs to be cautiously referenced.

with NMNE [18].

follow-up [20].

*4.1.2.2 Complex behavioral interventions*

**58**

control training in the daytime. To maximize the effect, the FSHT needs to be overlearned (giving extra fluids at bedtime after successfully becoming dry). Specific implementation steps of DBT and FSHT have been described by Brown and Glazener [22, 23]. In a Cochrane review of NE, complex behavioral interventions were compared with control, alarm, and other complex behavioral interventions. Moreover, complex behavioral interventions removing alarm were compared with control, alarm, and complex behavioral interventions supplemented by alarm. The conclusions were that DBT or FSHT was better than control in efficacy and relapse rate and marginally superior to alarm alone. Either complex behavioral interventions removing alarm or control intervention was inferior to alarm alone or complex behavioral interventions supplemented by alarm. There is no evidence for the comparison between complex behavioral interventions removing alarm and control. Additionally, adverse events were not described by the trials [23]. Unfortunately, the included studies in the systematic review have some limitations including small scale, small quantity, and poor quality. Besides, it has to be mentioned that the interventions are heavy burdens on families.

Alarm and reward system are the components of arousal therapy/training, which was reported to have a high efficacy and low relapse rate in an early literature [24]. However, they have not been recommended by the guideline [10] because there is not enough clinical evidence, which is similar to FSHT [25].

#### *4.1.2.3 Nonbehavioral interventions*

Biofeedback therapy and electrical stimulation therapy were originally used to treat voiding dysfunction, and now they have been tried to treat refractory MNE or PNE with a reported good efficacy. Dr. Hoekx and his colleagues prospectively evaluated the effect of bladder biofeedback in 21 boys and 3 girls (mean age 10.4 years). After treatment 17/24 patients showed good response that means they achieved totally dry. During the 60-month follow-up, 4 patients were lost, 15 were dry at night, and 4 continued bed-wetting. The proportion of children with small bladder capacity in responders is much less than the one in non-responders [26]. In a randomized clinical trial published in 2015, 54 children with PNE were included and randomly divided into interferential (IF) electrical stimulation group and control group. A responding rate was reported as 55.5 and 22% in the IF and control group at the 1-year follow-up (P = 0.01), respectively. In terms of the mean number of dry nights per week and the mean improvement score, the IF group was superior compared to control group. Additionally, no adverse events were reported [27]. In another trial, children with refractory MNE were randomly assigned to intra-anal biofeedback with behavioral therapy, electrical stimulation with behavioral therapy, and pelvic floor muscle training groups. The trial stated a total efficacy of three groups in the outcomes and that intra-anal ES group was superior to BF training group. But in these three outcomes, the method to assess nighttime bladder capacity with morning first urine volume is not accurate [28]. In short, there is no adequate clinical evidence to determine the therapeutic effectiveness of these NE treatments (**Table 2**).


**Table 2.** *Categories of nonbehavioral interventions.*

#### **4.2 Alarm**

Alarm therapy, also known as enuretic alarm devices (EADs) or enuresis alarm treatment (EA), is a kind of therapy with sufficient evidence which shows a higher response rate and a superior long-time success than the control or other therapies. Although its relapse rate is still a little high, the addition of overlearning and dry bed training or avoiding penalties can reduce the rate by nearly half [29]. In terms of different types of alarms, there was no enough evidence to draw conclusions, neither did the comparison between alarm and other behavioral therapies [29]. Two other Cochrane reviews revealed that alarm had better effects than simple behavioral interventions, but not when compared with complex behavioral therapies [16, 23]. Some researchers believed the effect of alarm might be weakened if only the parents were waked by the alarm instead of the children. A result from Tsuji's study showed whether the parents or children themselves are waked by the alarm or the effectiveness of alarm is equal [30]. Apos E. et al.'s study published in 2018 stated excellent effects of alarm therapy for MNE, NMNE, PNE, and SNE children using alarm therapy and especially for NMNE children [31]. The ICCS guideline also recommended that the alarm should be considered as the therapeutic option for every child. Furthermore, those children who have motivated parents should be given a priority [14].

It has to be mentioned that alarm does not have an immediate effect. Normally, it often needs to take a period of time to achieve the expected efficacy. The appropriate course recommended by the ICCS is 2–3 months until children achieve 14 consecutive dry nights or the effect is not good [14]. Similarly, the ICS's recommendation is to evaluate the efficacy of alarm after at least 6–8 weeks [12]. It also states that the efficacy will increase with treatment duration; however, the ideal course of alarm has not been introduced [12]. In one study, a total of 455 children with PMNE were randomly divided into three groups and received 3, 4, and 5 months of uninterrupted alarm treatment, respectively. The results showed that children with 16–20 weeks' treatment had better curative effect [32]. Unfortunately, this study did not observe the effect with a longer follow-up. So we cannot conclude if the longer treatment can further increase the effect of alarm. In another study, NE children who were ineffective after 3 months' alarm treatment were randomized into two groups to receive a repeat alarm treatment for ≥3 months without interval and with an interval of more than 6 months, separately. The success rate in the latter group was significantly higher than the former, which means repeat alarm therapy with at least one interval may reawaken children's response [33]. Despite the small sample size, this study may provide new ideas for children who have no response to alarm treatment.

The possible mechanism of alarm therapy may be a gradual establishment of a conditioned reflex between bladder filling and waking. Evidence showed that it could increase the prepulse inhibition (PPI), similar to the effect of desaminoarginine vasopressin (dDAVP), which suggested that the alarm could also promote the maturation of the reflex control of NE [34]. In addition, a study reported that children's daytime functional bladder capacity increased markedly after treatment with alarm [35]. Therefore, the efficacy of alarm on children with NE may be achieved through multiple effects.

#### **4.3 Desmopressin**

Desmopressin is an arginine vasopressin analog that enhances the reabsorption of water by the distal convoluted tubules and collecting ducts of the kidney and inhibits the secretion of aldosterone. Schulz-Juergensen et al.'s study published in 2007 showed that 1-desamino-8-d-arginine vasopressin (dDAVP) could make

**61**

*Advances in Treatment of Nocturnal Enuresis in Children*

PMNE children's PPI upregulate to the age-related normal level. The authors offered a different explanation about dDAVP that it not only had a role in the kidney but also acted as a central neurotransmitter which has a positive effect on the delayed maturation of NE children's micturition reflex [36]. According to the results of this study, desmopressin has the ability to cure a substantial group of children with NE in theory. However, it is more complicated in practice with problems of how to choose the potential suitable children for desmopressin therapy. Moreover, what is the appropriate dose and course of treatment are also big issues. To assess the effect of desmopressin, a number of studies have been performed. Evidence showed that it could significantly reduce bed-wetting by 1–2 nights per week during the treatment, but there is no difference in wet nights per week compared with the placebo group. Additionally, when comparing with alarm therapy, lower effectiveness and higher subsequent relapse rate were reported in the desmopressin group according

In general, children with nocturnal polyuria are suitable for desmopressin therapy. Basically, we can identify this subtype of MNE using the bladder diary. However, there is an evidence showing that children with NE may not present continuous nocturnal polyuria. Nocturnal urine production increases significantly on wet nights than the dry nights. Children without abnormal increase in nocturnal urine production do not respond to desmopressin [38]. This study revealed the polyuria characteristics for a subgroup of NE children and confirmed the efficacy of desmopressin for these children. Furthermore, some other studies also showed that desmopressin was not effective in children with low functional bladder capacity [39] and those with abnormal bladder volume and wall thickness (BVWT) [40], indicating that desmopressin's clinical use should carefully identify children with

Referring to appropriate dose of desmopressin, there is an insufficient evidence to determine whether higher dose is more effective or not [37]. The recommended safe dose is 0.2–0.4 mg for tablets and 120–240 μg for melt formulation [14]. There is no enough evidence to state what is the appropriate course of treatment. Because of high relapse rate after treatment, it is advised to gradually reduce the drug dose instead of stopping it directly at the time of getting a complete response. For long-term safety, desmopressin is proven to be safe enough to use for several years. Water intoxication with hyponatremia is only a severe adverse event that needs to be concerned. Fluid restriction of 200 ml or less for the whole night is advised with desmopressin treatment [14]. Moreover, nasal spray reports more hyponatremia

Anticholinergic drugs are widely used for the management of NE since they can bind to choline receptors and produce antagonistic activity against acetylcholine and consequently relieve detrusor overactivity. They can be classified into M and N receptor blockers according to their selectivity for different receptors. M receptor blockers, also called as antimuscarinics, are more commonly used to treat NE. Generally, M receptors consist of five different subtypes, including M1, M2, M3, M4, and M5. Of those, M2 and M3 subtypes are mainly distributed in the bladder wall, and M3 has an upregulated expression in patients with overactive bladder.

Therefore, the therapeutic mechanism of antimuscarinics is to inhibit

the bladder M receptor, relax the detrusor, and consequently expand the bladder capacity. The mechanism determines that antimuscarinic drugs should be mainly used in treatment of NE children who are suffering from latent bladder smooth muscle spasm, detrusor overactivity, or decreased functional bladder capacity.

*DOI: http://dx.doi.org/10.5772/intechopen.89106*

to a Cochrane review [37].

potential bladder dysfunction.

than oral formulations [41].

**4.4 Pharmacotherapy (other than desmopressin)**

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

Alarm therapy, also known as enuretic alarm devices (EADs) or enuresis alarm treatment (EA), is a kind of therapy with sufficient evidence which shows a higher response rate and a superior long-time success than the control or other therapies. Although its relapse rate is still a little high, the addition of overlearning and dry bed training or avoiding penalties can reduce the rate by nearly half [29]. In terms of different types of alarms, there was no enough evidence to draw conclusions, neither did the comparison between alarm and other behavioral therapies [29]. Two other Cochrane reviews revealed that alarm had better effects than simple behavioral interventions, but not when compared with complex behavioral therapies [16, 23]. Some researchers believed the effect of alarm might be weakened if only the parents were waked by the alarm instead of the children. A result from Tsuji's study showed whether the parents or children themselves are waked by the alarm or the effectiveness of alarm is equal [30]. Apos E. et al.'s study published in 2018 stated excellent effects of alarm therapy for MNE, NMNE, PNE, and SNE children using alarm therapy and especially for NMNE children [31]. The ICCS guideline also recommended that the alarm should be considered as the therapeutic option for every child. Furthermore, those children who have motivated parents should be

It has to be mentioned that alarm does not have an immediate effect. Normally, it often needs to take a period of time to achieve the expected efficacy. The appropriate course recommended by the ICCS is 2–3 months until children achieve 14 consecutive dry nights or the effect is not good [14]. Similarly, the ICS's recommendation is to evaluate the efficacy of alarm after at least 6–8 weeks [12]. It also states that the efficacy will increase with treatment duration; however, the ideal course of alarm has not been introduced [12]. In one study, a total of 455 children with PMNE were randomly divided into three groups and received 3, 4, and 5 months of uninterrupted alarm treatment, respectively. The results showed that children with 16–20 weeks' treatment had better curative effect [32]. Unfortunately, this study did not observe the effect with a longer follow-up. So we cannot conclude if the longer treatment can further increase the effect of alarm. In another study, NE children who were ineffective after 3 months' alarm treatment were randomized into two groups to receive a repeat alarm treatment for ≥3 months without interval and with an interval of more than 6 months, separately. The success rate in the latter group was significantly higher than the former, which means repeat alarm therapy with at least one interval may reawaken children's response [33]. Despite the small sample size, this study may

provide new ideas for children who have no response to alarm treatment.

The possible mechanism of alarm therapy may be a gradual establishment of a conditioned reflex between bladder filling and waking. Evidence showed that it could increase the prepulse inhibition (PPI), similar to the effect of desaminoarginine vasopressin (dDAVP), which suggested that the alarm could also promote the maturation of the reflex control of NE [34]. In addition, a study reported that children's daytime functional bladder capacity increased markedly after treatment with alarm [35]. Therefore, the efficacy of alarm on children with NE may be

Desmopressin is an arginine vasopressin analog that enhances the reabsorption of water by the distal convoluted tubules and collecting ducts of the kidney and inhibits the secretion of aldosterone. Schulz-Juergensen et al.'s study published in 2007 showed that 1-desamino-8-d-arginine vasopressin (dDAVP) could make

**4.2 Alarm**

given a priority [14].

**60**

achieved through multiple effects.

**4.3 Desmopressin**

PMNE children's PPI upregulate to the age-related normal level. The authors offered a different explanation about dDAVP that it not only had a role in the kidney but also acted as a central neurotransmitter which has a positive effect on the delayed maturation of NE children's micturition reflex [36]. According to the results of this study, desmopressin has the ability to cure a substantial group of children with NE in theory. However, it is more complicated in practice with problems of how to choose the potential suitable children for desmopressin therapy. Moreover, what is the appropriate dose and course of treatment are also big issues. To assess the effect of desmopressin, a number of studies have been performed. Evidence showed that it could significantly reduce bed-wetting by 1–2 nights per week during the treatment, but there is no difference in wet nights per week compared with the placebo group. Additionally, when comparing with alarm therapy, lower effectiveness and higher subsequent relapse rate were reported in the desmopressin group according to a Cochrane review [37].

In general, children with nocturnal polyuria are suitable for desmopressin therapy. Basically, we can identify this subtype of MNE using the bladder diary. However, there is an evidence showing that children with NE may not present continuous nocturnal polyuria. Nocturnal urine production increases significantly on wet nights than the dry nights. Children without abnormal increase in nocturnal urine production do not respond to desmopressin [38]. This study revealed the polyuria characteristics for a subgroup of NE children and confirmed the efficacy of desmopressin for these children. Furthermore, some other studies also showed that desmopressin was not effective in children with low functional bladder capacity [39] and those with abnormal bladder volume and wall thickness (BVWT) [40], indicating that desmopressin's clinical use should carefully identify children with potential bladder dysfunction.

Referring to appropriate dose of desmopressin, there is an insufficient evidence to determine whether higher dose is more effective or not [37]. The recommended safe dose is 0.2–0.4 mg for tablets and 120–240 μg for melt formulation [14]. There is no enough evidence to state what is the appropriate course of treatment. Because of high relapse rate after treatment, it is advised to gradually reduce the drug dose instead of stopping it directly at the time of getting a complete response. For long-term safety, desmopressin is proven to be safe enough to use for several years. Water intoxication with hyponatremia is only a severe adverse event that needs to be concerned. Fluid restriction of 200 ml or less for the whole night is advised with desmopressin treatment [14]. Moreover, nasal spray reports more hyponatremia than oral formulations [41].

#### **4.4 Pharmacotherapy (other than desmopressin)**

Anticholinergic drugs are widely used for the management of NE since they can bind to choline receptors and produce antagonistic activity against acetylcholine and consequently relieve detrusor overactivity. They can be classified into M and N receptor blockers according to their selectivity for different receptors. M receptor blockers, also called as antimuscarinics, are more commonly used to treat NE. Generally, M receptors consist of five different subtypes, including M1, M2, M3, M4, and M5. Of those, M2 and M3 subtypes are mainly distributed in the bladder wall, and M3 has an upregulated expression in patients with overactive bladder. Therefore, the therapeutic mechanism of antimuscarinics is to inhibit the bladder M receptor, relax the detrusor, and consequently expand the bladder capacity. The mechanism determines that antimuscarinic drugs should be mainly used in treatment of NE children who are suffering from latent bladder smooth muscle spasm, detrusor overactivity, or decreased functional bladder capacity.

This kind of children usually has daytime symptoms of lower urinary tract and is classified as NMNE. However, some children diagnosed as MNE are also suitable for anticholinergic drug therapy because they have only nighttime detrusor overactivity or mild urinary tract symptoms during daytime. For children who do not respond to alarm or desmopressin therapy, anticholinergic agents are usually a kind of therapeutic option. The clinical application of anticholinergic drugs should focus on how to identify the children with indications through bladder diary and other diagnostic techniques. Studies to evaluate the efficacy of anticholinergic drugs and their combination with alarm or desmopressin on these children should be conducted as well.

Differing from anticholinergic drugs, the mechanism of tricyclic drugs in the treatment of NE is still unclear. The possible mechanism includes inhibiting rapid eye movement sleep to promote sleep arousal and stimulating antidiuretic hormone secretion. A Cochrane review showed that tricyclic drugs could reduce about one wet night per week, but most children relapsed after treatment which is similar to desmopressin and inferior to alarm [42]. In addition, most tricyclic drugs may cause serious side effects such as cardiotoxicity, so they are only used for the treatment of refractory or therapy-resistant NE. An exception is reboxetine. Neveus and his colleagues attempted to treat children with therapy-resistant NE using reboxetine, and they found that 59% of the patients reached a full response after 4 weeks of treatment. Moreover, during treatment, no significant cardiac toxicity was reported [43]. Lundmark et al. used reboxetine to treat therapy-resistant NE children and also achieved good results without significant cardiac adverse events [44]. Therefore, reboxetine may be a good therapeutic option instead of imipramine, but its effectiveness and safety need more clinical studies to prove.

#### **4.5 Complementary and alternative approaches**

Although a large amount of evidence has shown the effectiveness of conventional treatment including alarm and pharmacotherapy on NE [31, 45], these approaches cannot meet all the needs of the children and their parents. It is reported that as high as 30% of families discontinue the treatment of alarm on their own reason [46]. On the other hand, the side effects related to medications bother both children and their family members. Therefore, a number of parents are more likely to seek help from complementary and alternative medicine for their children. Being outside of conventional medicine, complementary and alternative medicine includes a series of medical approaches, such as acupuncture, herbal therapy, and massage. Recently, an increasing evidence has shown the efficacy of complementary and alternative medicine on management of NE.

#### *4.5.1 Acupuncture*

Acupuncture, as a component of traditional Chinese medicine, has been used to manage a number of chronic diseases. Even though acupuncture originates in China, its efficacy on various urological diseases has been recognized in industrial world [47]. A number of studies have demonstrated the effectiveness of acupuncture in treatment of NE. In a single-arm trial, Bjorkstrom et al. [48] showed that an 8-week treatment with 20 sessions of acupuncture decreased the episodes of NE and the sleep arousal threshold significantly in 65 and 50% of children, respectively, at the followup of 6 months. Another study further revealed that acupuncture might increase the nocturnal bladder capacity significantly in responders [49]. To assess the effect of acupuncture on NE, several systematic reviews were conducted. As presented in a part of Cochrane systematic review [50], Glazener et al. showed that acupuncture

**63**

*4.5.2 Herbal therapy*

*Advances in Treatment of Nocturnal Enuresis in Children*

might result in a more significant improvement for children with NE than sham intervention. Moreover, acupuncture seemed to have a lower failure rate than combination therapy with meclofenoxate, oryzanol, and thiamine. Six years later, the updated Cochrane systematic review [50] demonstrated the same result. Another systematic review showed that acupuncture in conjunction with other treatment could reduce the number of NE more significantly than other treatment alone [51]. It needs to be mentioned that some methodological limitations have to be taken into consideration when we analyze the evidence. These systematic reviews included the nonrandomized and quasi-randomized studies besides randomized controlled trials, which may weaken the level of evidence. To provide the high quality of evidence, a recent published systematic review excluded nonrandomized and quasi-randomized trials and showed that acupuncture might be more effective in management of NE than sham procedure or drug treatment [52]. However, some studies with the intervention of acupoint injection were included in the systematic review, which may make the results controversial. As is known, acupuncture only provides physical effect, while

both physical and chemical effects are involved in acupoint injection.

sham procedure, and herbal therapy, respectively.

magnus [54], which may cause an antidiuretic effect.

To further provide evidence, we designed and conducted a systematic review. After performing a comprehensive search of medical literature, including Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CBM, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform, on February 22, 2019, a total of 238 randomized controlled trials were reviewed, and 10 of them with 953 randomized participants (441 in acupuncture group and 412 in control group) were included. We found that compared with the other treatment, acupuncture resulted in significantly higher complete response rate [OR = 2.41, 95%CI (1.41, 4.93) P = 0.002], so did the significance when compared with conventional drug, sham procedure, and herbal therapy, respectively. Moreover, although acupuncture did not reduce the average number of NE in comparison with other treatment, a significant decrease was found when compared to the sham intervention [MD = −1.49, 95%CI (−2.26, −0.72) P = 0.0002]. In terms of adverse events, there was no significant difference between acupuncture and other treatment [OR = 0.62, 95%CI (0.04, 8.72) P = 0.72]. Based on our results, acupuncture may have a better effect in management of NE, when compared to conventional drug,

The potential mechanism of acupuncture's effectiveness in managing NE might be the regulation on bladder function and secretion of antidiuretic hormone. A study assessed the effect of acupuncture on urodynamic parameters in children with NE and found acupuncture could suppress the detrusor overactivity [53]. On the other hand, an animal experiment showed that acupuncture could downregulate the concentration of arginine vasopressin in the hypothalamic paraventricular nucleus and upregulate the concentration of arginine vasopressin in the hypothalamic supraoptic nucleus, periaqueductal gray, caudate nucleus, and nucleus raphe

Herbal therapy is an important component of traditional medicine. About 3500 years ago, Papyrus Ebers described that cypress, juniper berries, and beer might be used to treat NE, which is the earliest record for the treatment of NE. Although there is lack of enough evidence, some herbs, such as St John's wort (*Hypericum perforatum*), infusions of horsetail, or corn silk (*Zea mays*), are considered to be helpful to regulate bladder function [55]. Hosein et al. performed a double-blind randomized controlled trial to evaluate the effectiveness of chamomile oil in treating NE, in which 80 patients were allocated to receive chamomile

*DOI: http://dx.doi.org/10.5772/intechopen.89106*

#### *Advances in Treatment of Nocturnal Enuresis in Children DOI: http://dx.doi.org/10.5772/intechopen.89106*

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

conducted as well.

This kind of children usually has daytime symptoms of lower urinary tract and is classified as NMNE. However, some children diagnosed as MNE are also suitable for anticholinergic drug therapy because they have only nighttime detrusor overactivity or mild urinary tract symptoms during daytime. For children who do not respond to alarm or desmopressin therapy, anticholinergic agents are usually a kind of therapeutic option. The clinical application of anticholinergic drugs should focus on how to identify the children with indications through bladder diary and other diagnostic techniques. Studies to evaluate the efficacy of anticholinergic drugs and their combination with alarm or desmopressin on these children should be

Differing from anticholinergic drugs, the mechanism of tricyclic drugs in the treatment of NE is still unclear. The possible mechanism includes inhibiting rapid eye movement sleep to promote sleep arousal and stimulating antidiuretic hormone secretion. A Cochrane review showed that tricyclic drugs could reduce about one wet night per week, but most children relapsed after treatment which is similar to desmopressin and inferior to alarm [42]. In addition, most tricyclic drugs may cause serious side effects such as cardiotoxicity, so they are only used for the treatment of refractory or therapy-resistant NE. An exception is reboxetine. Neveus and his colleagues attempted to treat children with therapy-resistant NE using reboxetine, and they found that 59% of the patients reached a full response after 4 weeks of treatment. Moreover, during treatment, no significant cardiac toxicity was reported

[43]. Lundmark et al. used reboxetine to treat therapy-resistant NE children and also achieved good results without significant cardiac adverse events [44]. Therefore, reboxetine may be a good therapeutic option instead of imipramine, but

Although a large amount of evidence has shown the effectiveness of conventional treatment including alarm and pharmacotherapy on NE [31, 45], these approaches cannot meet all the needs of the children and their parents. It is

reported that as high as 30% of families discontinue the treatment of alarm on their own reason [46]. On the other hand, the side effects related to medications bother both children and their family members. Therefore, a number of parents are more likely to seek help from complementary and alternative medicine for their children. Being outside of conventional medicine, complementary and alternative medicine includes a series of medical approaches, such as acupuncture, herbal therapy, and massage. Recently, an increasing evidence has shown the efficacy of complemen-

Acupuncture, as a component of traditional Chinese medicine, has been used to manage a number of chronic diseases. Even though acupuncture originates in China, its efficacy on various urological diseases has been recognized in industrial world [47]. A number of studies have demonstrated the effectiveness of acupuncture in treatment of NE. In a single-arm trial, Bjorkstrom et al. [48] showed that an 8-week treatment with 20 sessions of acupuncture decreased the episodes of NE and the sleep arousal threshold significantly in 65 and 50% of children, respectively, at the followup of 6 months. Another study further revealed that acupuncture might increase the nocturnal bladder capacity significantly in responders [49]. To assess the effect of acupuncture on NE, several systematic reviews were conducted. As presented in a part of Cochrane systematic review [50], Glazener et al. showed that acupuncture

its effectiveness and safety need more clinical studies to prove.

**4.5 Complementary and alternative approaches**

tary and alternative medicine on management of NE.

**62**

*4.5.1 Acupuncture*

might result in a more significant improvement for children with NE than sham intervention. Moreover, acupuncture seemed to have a lower failure rate than combination therapy with meclofenoxate, oryzanol, and thiamine. Six years later, the updated Cochrane systematic review [50] demonstrated the same result. Another systematic review showed that acupuncture in conjunction with other treatment could reduce the number of NE more significantly than other treatment alone [51]. It needs to be mentioned that some methodological limitations have to be taken into consideration when we analyze the evidence. These systematic reviews included the nonrandomized and quasi-randomized studies besides randomized controlled trials, which may weaken the level of evidence. To provide the high quality of evidence, a recent published systematic review excluded nonrandomized and quasi-randomized trials and showed that acupuncture might be more effective in management of NE than sham procedure or drug treatment [52]. However, some studies with the intervention of acupoint injection were included in the systematic review, which may make the results controversial. As is known, acupuncture only provides physical effect, while both physical and chemical effects are involved in acupoint injection.

To further provide evidence, we designed and conducted a systematic review. After performing a comprehensive search of medical literature, including Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CBM, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform, on February 22, 2019, a total of 238 randomized controlled trials were reviewed, and 10 of them with 953 randomized participants (441 in acupuncture group and 412 in control group) were included. We found that compared with the other treatment, acupuncture resulted in significantly higher complete response rate [OR = 2.41, 95%CI (1.41, 4.93) P = 0.002], so did the significance when compared with conventional drug, sham procedure, and herbal therapy, respectively. Moreover, although acupuncture did not reduce the average number of NE in comparison with other treatment, a significant decrease was found when compared to the sham intervention [MD = −1.49, 95%CI (−2.26, −0.72) P = 0.0002]. In terms of adverse events, there was no significant difference between acupuncture and other treatment [OR = 0.62, 95%CI (0.04, 8.72) P = 0.72]. Based on our results, acupuncture may have a better effect in management of NE, when compared to conventional drug, sham procedure, and herbal therapy, respectively.

The potential mechanism of acupuncture's effectiveness in managing NE might be the regulation on bladder function and secretion of antidiuretic hormone. A study assessed the effect of acupuncture on urodynamic parameters in children with NE and found acupuncture could suppress the detrusor overactivity [53]. On the other hand, an animal experiment showed that acupuncture could downregulate the concentration of arginine vasopressin in the hypothalamic paraventricular nucleus and upregulate the concentration of arginine vasopressin in the hypothalamic supraoptic nucleus, periaqueductal gray, caudate nucleus, and nucleus raphe magnus [54], which may cause an antidiuretic effect.

#### *4.5.2 Herbal therapy*

Herbal therapy is an important component of traditional medicine. About 3500 years ago, Papyrus Ebers described that cypress, juniper berries, and beer might be used to treat NE, which is the earliest record for the treatment of NE. Although there is lack of enough evidence, some herbs, such as St John's wort (*Hypericum perforatum*), infusions of horsetail, or corn silk (*Zea mays*), are considered to be helpful to regulate bladder function [55]. Hosein et al. performed a double-blind randomized controlled trial to evaluate the effectiveness of chamomile oil in treating NE, in which 80 patients were allocated to receive chamomile

oil or placebo. After 2 weeks treatment, the patients' mean wet night frequency in chamomile oil group decreased from 8.2 to 5.6 nights/2 weeks, while no significant difference was found in placebo group [56]. We hope more clinical trials can provide more evidence for the efficacy of herbal therapy in future.

#### *4.5.3 Massage and chiropractic*

Both massage and chiropractic are a kind of manipulative therapy acting on the body with appropriate pressure. The former focuses on the relaxation of muscle, while the latter centers on the regulation of spinal articulations. They can be the therapeutic options for NE since their effectiveness has been reported. An early study attempted to treat five children with NE using massage which pressed the acupoint located in the creases between the first and the second and the third phalanx of the 5th finger. After an average of 20 sessions of therapy, two children achieved complete recovery, and one got partial recovery [57]. In another study, Yuksek et al. performed an efficacy comparison of massage with oxybutynin. After 6 months treatment, 83.3% of patients in massage group experienced a significant improvement, which is better than 58.3% in oxybutynin group [58].

In a case series study, 171 children with NE were treated by chiropractic. After 2 weeks treatment, the median episodes of NE decreased from 7.0 per week at baseline to 5.6 per week and further dropped to 4.0 per week at the end of treatment [59]. Another finding of the study is that the more severe symptoms children had, the less benefit they got from the treatment, which means those with mild to moderate NE might be suitable for chiropractic. Reed et al. designed and conducted a 10-week controlled clinical trial, in which children with NE received chiropractic or sham intervention. After the treatment, a significant reduction was observed in children's mean wet night frequency (from 9.1 to 6.7 nights/2 weeks) in chiropractic group. By contrast, the counterpart in sham intervention group did not change markedly (12.1 vs 12.2 nights/2 weeks) [60]. Van Poecke and his colleague found that the resolution rate within 1 year in children who received chiropractic was about 66.6% after analyzing the data of 33 patient records [61].

#### **5. New about diagnostic and treatment**

Enuretic bladder capacity is a big issue discussed in some recent research. Researchers are more likely to use the reduction in maximum voiding volume (MVV) on bladder diary to determine the decreased nocturnal bladder capacity (NBC). However, it might be unreasonable because a study found the enuretic bladder capacity of enuresis children was significantly less than their daytime functional bladder capacity (FBC), while healthy children's NBC was the same as FBC [62]. Kim et al.'s study also showed that the proportion of NE children with small NBC and small MVV was quite different. The accuracy using decreased MVV to identify small NBC is only medium to low [63]. Another study performed by Borg et al. measured the difference in diaper weight between the early part and the later part of the night, as the enuretic bladder capacity, in MNE children with normal MVV, and found that 82% of children had less bladder capacity than MVV during enuresis, even less than 65% of expected bladder capacity [64]. These studies indicate that although small MVV can be used to determine the reduction of FBC, it cannot assess accurately NBC or enuretic bladder capacity. If pediatricians manage MNE children with normal MVV with desmopressin following the ICCS guidelines, these children may still experience nocturnal

**65**

*Advances in Treatment of Nocturnal Enuresis in Children*

taken for a long time and then gradually reduced.

tion of first-line therapy and second-line therapy.

response to these two therapies may be mostly overlapped.

enuresis due to a mismatch between bladder capacity and urine volume at night. Therefore, a new method for assessing NBC and enuretic bladder capacity needs

Barroso et al. assessed the efficacy of a new device, which is the combination of alarm and electrical stimulation to the pelvic floor muscles, for NE. This device presented an advantage that helps children to achieve no wet beds during the period of treatment. On the one hand, pelvic floor muscle contraction induced by electrical stimulus may cause an increased urethral closure pressure, which allows children to keep dry during nighttime. On the other hand, alarm would also be triggered by the humidity sensor, and children would be waked to void [65]. This device needs more trials to determine its effectiveness and safety. Additionally, there was an intelligent autonomous alarm using ultrasound and smartphone ML techniques raised in 2019. It could monitor the bladder and trigger before the voiding desire. It also has the advantage to achieve totally dry bed

Standard therapy should be applied to every child when he first visits the clinic. Then clinicians follow the diagnosis algorithm to distinguish MNE from NMNE and determine which subtype the child is. According to the ICCS's guideline [10], MNE children with normal nocturnal urine volume (normal or reduced MVV) should choose the alarm therapy. It is believed as the most effective single-therapy with the lower recurrence rate and has efficacy for most types of MNE, even NMNE. The addition of overlearning can reduce the relapse rate of alarm. Therefore, it is necessary to perform overlearning after the success of the alarm treatment. Complex behavioral therapies supplemented by alarm are more effective than alarm and can reduce the recurrence rate. It can be advised to families with better motivation and seeking for better efficacy. Desmopressin should be used for the treatment of MNE children with polyuria (normal or reduced MVV). To avoid relapse, the drug can be

The guideline recommended small MVV and NP children to use combination therapy of alarm and desmopressin [10]. The addition of alarm can increase the long-term efficacy of desmopressin [37]. However, combination therapy seems not to reduce the number of children who do not achieve 14 consecutive dry nights compared with alarm alone [29], indicating that patients who do not have full

For refractory NE, clinicians should reassess children's potential physiological malformations and neurogenic bladder diseases using MRI, urodynamics, cystoscopy, urography, etc. if necessary. After first-line treatment failure, children with detrusor overactivity or decreasing functional bladder capacity can choose anticholinergic drugs. Other children can choose tricyclic drugs, biofeedback therapy, electrical stimulation interventions, acupuncture, massage and so on, or a combina-

In summary, after meticulous diagnosis and assessment and appropriate treatment with sufficient evidence, most MNE children can get a great relief or even cure.

*DOI: http://dx.doi.org/10.5772/intechopen.89106*

to be explored.

during treatment [66].

**6. Conclusions**

*Advances in Treatment of Nocturnal Enuresis in Children DOI: http://dx.doi.org/10.5772/intechopen.89106*

enuresis due to a mismatch between bladder capacity and urine volume at night. Therefore, a new method for assessing NBC and enuretic bladder capacity needs to be explored.

Barroso et al. assessed the efficacy of a new device, which is the combination of alarm and electrical stimulation to the pelvic floor muscles, for NE. This device presented an advantage that helps children to achieve no wet beds during the period of treatment. On the one hand, pelvic floor muscle contraction induced by electrical stimulus may cause an increased urethral closure pressure, which allows children to keep dry during nighttime. On the other hand, alarm would also be triggered by the humidity sensor, and children would be waked to void [65]. This device needs more trials to determine its effectiveness and safety. Additionally, there was an intelligent autonomous alarm using ultrasound and smartphone ML techniques raised in 2019. It could monitor the bladder and trigger before the voiding desire. It also has the advantage to achieve totally dry bed during treatment [66].

#### **6. Conclusions**

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

*4.5.3 Massage and chiropractic*

oxybutynin group [58].

provide more evidence for the efficacy of herbal therapy in future.

about 66.6% after analyzing the data of 33 patient records [61].

**5. New about diagnostic and treatment**

oil or placebo. After 2 weeks treatment, the patients' mean wet night frequency in chamomile oil group decreased from 8.2 to 5.6 nights/2 weeks, while no significant difference was found in placebo group [56]. We hope more clinical trials can

Both massage and chiropractic are a kind of manipulative therapy acting on the body with appropriate pressure. The former focuses on the relaxation of muscle, while the latter centers on the regulation of spinal articulations. They can be the therapeutic options for NE since their effectiveness has been reported. An early study attempted to treat five children with NE using massage which pressed the acupoint located in the creases between the first and the second and the third phalanx of the 5th finger. After an average of 20 sessions of therapy, two children achieved complete recovery, and one got partial recovery [57]. In another study, Yuksek et al. performed an efficacy comparison of massage with oxybutynin. After 6 months treatment, 83.3% of patients in massage group experienced a significant improvement, which is better than 58.3% in

In a case series study, 171 children with NE were treated by chiropractic. After 2 weeks treatment, the median episodes of NE decreased from 7.0 per week at baseline to 5.6 per week and further dropped to 4.0 per week at the end of treatment [59]. Another finding of the study is that the more severe symptoms children had, the less benefit they got from the treatment, which means those with mild to moderate NE might be suitable for chiropractic. Reed et al. designed and conducted a 10-week controlled clinical trial, in which children with NE received chiropractic or sham intervention. After the treatment, a significant reduction was observed in children's mean wet night frequency (from 9.1 to 6.7 nights/2 weeks) in chiropractic group. By contrast, the counterpart in sham intervention group did not change markedly (12.1 vs 12.2 nights/2 weeks) [60]. Van Poecke and his colleague found that the resolution rate within 1 year in children who received chiropractic was

Enuretic bladder capacity is a big issue discussed in some recent research. Researchers are more likely to use the reduction in maximum voiding volume (MVV) on bladder diary to determine the decreased nocturnal bladder capacity (NBC). However, it might be unreasonable because a study found the enuretic bladder capacity of enuresis children was significantly less than their daytime functional bladder capacity (FBC), while healthy children's NBC was the same as FBC [62]. Kim et al.'s study also showed that the proportion of NE children with small NBC and small MVV was quite different. The accuracy using decreased MVV to identify small NBC is only medium to low [63]. Another study performed by Borg et al. measured the difference in diaper weight between the early part and the later part of the night, as the enuretic bladder capacity, in MNE children with normal MVV, and found that 82% of children had less bladder capacity than MVV during enuresis, even less than 65% of expected bladder capacity [64]. These studies indicate that although small MVV can be used to determine the reduction of FBC, it cannot assess accurately NBC or enuretic bladder capacity. If pediatricians manage MNE children with normal MVV with desmopressin following the ICCS guidelines, these children may still experience nocturnal

**64**

Standard therapy should be applied to every child when he first visits the clinic. Then clinicians follow the diagnosis algorithm to distinguish MNE from NMNE and determine which subtype the child is. According to the ICCS's guideline [10], MNE children with normal nocturnal urine volume (normal or reduced MVV) should choose the alarm therapy. It is believed as the most effective single-therapy with the lower recurrence rate and has efficacy for most types of MNE, even NMNE. The addition of overlearning can reduce the relapse rate of alarm. Therefore, it is necessary to perform overlearning after the success of the alarm treatment. Complex behavioral therapies supplemented by alarm are more effective than alarm and can reduce the recurrence rate. It can be advised to families with better motivation and seeking for better efficacy. Desmopressin should be used for the treatment of MNE children with polyuria (normal or reduced MVV). To avoid relapse, the drug can be taken for a long time and then gradually reduced.

The guideline recommended small MVV and NP children to use combination therapy of alarm and desmopressin [10]. The addition of alarm can increase the long-term efficacy of desmopressin [37]. However, combination therapy seems not to reduce the number of children who do not achieve 14 consecutive dry nights compared with alarm alone [29], indicating that patients who do not have full response to these two therapies may be mostly overlapped.

For refractory NE, clinicians should reassess children's potential physiological malformations and neurogenic bladder diseases using MRI, urodynamics, cystoscopy, urography, etc. if necessary. After first-line treatment failure, children with detrusor overactivity or decreasing functional bladder capacity can choose anticholinergic drugs. Other children can choose tricyclic drugs, biofeedback therapy, electrical stimulation interventions, acupuncture, massage and so on, or a combination of first-line therapy and second-line therapy.

In summary, after meticulous diagnosis and assessment and appropriate treatment with sufficient evidence, most MNE children can get a great relief or even cure. *Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

#### **Author details**

Bingying Zhou\*, Jianxin Lu, Peiqi Shi and Yifang An Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China

\*Address all correspondence to: zhou1173538131@163.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**67**

2004;**46**(1):58-63

*Advances in Treatment of Nocturnal Enuresis in Children*

[8] Jarvelin M, Vikevainentervonen L, Moilanen I, et al. Enuresis in Seven‐ Year‐Old Children. Acta Paediatrica.

[9] Wen JG, Wang QW, Chen Y, et al. An epidemiological study of primary nocturnal enuresis in Chinese children and adolescents. European Urology.

[10] Walle JV, Rittig S, Bauer S, et al. Practical consensus guidelines for the management of enuresis. European Journal of Pediatrics.

[11] Dibianco JM, Morley C, Alomar O. Nocturnal enuresis: A topic review and institution experience. Avicenna Journal of Medicine. 2014;**4**:77

[12] Tekgul S, Nijman R, Hoebeke P, Canning D, Bower W, von Gontard A. Diagnosis and management of urinary incontinence in childhood.Report

[13] Sorotzkin B. Nocturnal enuresis: Current perspectives. Clinical

Psychology Review. 1984;**4**(3):293-315

[14] Neveus T, Eggert P, Evans J, et al. Evaluation of and treatment for monosymptomatic enuresis: A standardization document from the international children's continence society. The Journal of Urology.

from the 4th International Consultation on Incontinence. Plymouth, UK: Health Publication

Ltd; 2009. pp. 701-792

2010;**183**(2):441-447

[15] Van Hoeck KJ, Bael A, Van Dessel E, et al. Do holding exercises or antimuscarinics increase maximum voided volume in monosymptomatic nocturnal enuresis? A randomized controlled trial in children. The Journal of Urology. 2007;**178**(5):2132-2136. DOI:

10.1016/j.juro.2007.07.051

1988;**77**(1):148-153

2006;**49**(6):1107-1113

2012;**171**(6):971-983

*DOI: http://dx.doi.org/10.5772/intechopen.89106*

[1] Austin PF, Bauer SB, Bower W, et al. The standardization of terminology of lower urinary tract function in children and adolescents: Update report from the Standardization Committee of the International Children's Continence Society. Journal of Urology. 2014;**6**:1863- 1865.e13. DOI: 10.1016/j.juro.2014.01.110

[2] Jain S, Bhatt GC. Advances in the management of primary

Child Health. 2016;**36**(1):7-14

[3] Bakhtiar K, Pournia Y,

2014:120686-120686

2018;**2**(1):e000311

2017;**35**(3):459-465

monosymptomatic nocturnal enuresis in children. Paediatrics and International

Ebrahimzadeh F, et al. Prevalence of nocturnal enuresis and its associated factors in primary school and preschool children of khorramabad in 2013. International Journal of Pediatrics.

[4] Mejias SG, Ramphul K. Nocturnal enuresis in children from Santo Domingo, Dominican Republic: A questionnaire study of prevalence and risk factors. BMJ Paediatrics Open.

[5] Hamed A, Yousf F, Hussein MM. Prevalence of nocturnal enuresis and related risk factors in school-age children in Egypt: An epidemiological study. World Journal of Urology.

[6] Sarici H, Telli O, Ozgur BC, et al. Prevalence of nocturnal enuresis and its influence on quality of life in schoolaged children. Journal of Pediatric Urology. 2016;**12**(3):159.e1-159.e6. DOI:

10.1016/j.jpurol.2015.11.011

[7] Gür E, Turhan P, Can G, et al. Enuresis: Prevalence, risk factors and urinary pathology among school children in Istanbul, Turkey. Pediatrics International: Official Journal of the Japan Pediatric Society.

**References**

*Advances in Treatment of Nocturnal Enuresis in Children DOI: http://dx.doi.org/10.5772/intechopen.89106*

#### **References**

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

**66**

**Author details**

China

Bingying Zhou\*, Jianxin Lu, Peiqi Shi and Yifang An

provided the original work is properly cited.

\*Address all correspondence to: zhou1173538131@163.com

Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing,

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

[1] Austin PF, Bauer SB, Bower W, et al. The standardization of terminology of lower urinary tract function in children and adolescents: Update report from the Standardization Committee of the International Children's Continence Society. Journal of Urology. 2014;**6**:1863- 1865.e13. DOI: 10.1016/j.juro.2014.01.110

[2] Jain S, Bhatt GC. Advances in the management of primary monosymptomatic nocturnal enuresis in children. Paediatrics and International Child Health. 2016;**36**(1):7-14

[3] Bakhtiar K, Pournia Y, Ebrahimzadeh F, et al. Prevalence of nocturnal enuresis and its associated factors in primary school and preschool children of khorramabad in 2013. International Journal of Pediatrics. 2014:120686-120686

[4] Mejias SG, Ramphul K. Nocturnal enuresis in children from Santo Domingo, Dominican Republic: A questionnaire study of prevalence and risk factors. BMJ Paediatrics Open. 2018;**2**(1):e000311

[5] Hamed A, Yousf F, Hussein MM. Prevalence of nocturnal enuresis and related risk factors in school-age children in Egypt: An epidemiological study. World Journal of Urology. 2017;**35**(3):459-465

[6] Sarici H, Telli O, Ozgur BC, et al. Prevalence of nocturnal enuresis and its influence on quality of life in schoolaged children. Journal of Pediatric Urology. 2016;**12**(3):159.e1-159.e6. DOI: 10.1016/j.jpurol.2015.11.011

[7] Gür E, Turhan P, Can G, et al. Enuresis: Prevalence, risk factors and urinary pathology among school children in Istanbul, Turkey. Pediatrics International: Official Journal of the Japan Pediatric Society. 2004;**46**(1):58-63

[8] Jarvelin M, Vikevainentervonen L, Moilanen I, et al. Enuresis in Seven‐ Year‐Old Children. Acta Paediatrica. 1988;**77**(1):148-153

[9] Wen JG, Wang QW, Chen Y, et al. An epidemiological study of primary nocturnal enuresis in Chinese children and adolescents. European Urology. 2006;**49**(6):1107-1113

[10] Walle JV, Rittig S, Bauer S, et al. Practical consensus guidelines for the management of enuresis. European Journal of Pediatrics. 2012;**171**(6):971-983

[11] Dibianco JM, Morley C, Alomar O. Nocturnal enuresis: A topic review and institution experience. Avicenna Journal of Medicine. 2014;**4**:77

[12] Tekgul S, Nijman R, Hoebeke P, Canning D, Bower W, von Gontard A. Diagnosis and management of urinary incontinence in childhood.Report from the 4th International Consultation on Incontinence. Plymouth, UK: Health Publication Ltd; 2009. pp. 701-792

[13] Sorotzkin B. Nocturnal enuresis: Current perspectives. Clinical Psychology Review. 1984;**4**(3):293-315

[14] Neveus T, Eggert P, Evans J, et al. Evaluation of and treatment for monosymptomatic enuresis: A standardization document from the international children's continence society. The Journal of Urology. 2010;**183**(2):441-447

[15] Van Hoeck KJ, Bael A, Van Dessel E, et al. Do holding exercises or antimuscarinics increase maximum voided volume in monosymptomatic nocturnal enuresis? A randomized controlled trial in children. The Journal of Urology. 2007;**178**(5):2132-2136. DOI: 10.1016/j.juro.2007.07.051

[16] Caldwell PHY, Nankivell G, Sureshkumar P. Simple behavioural interventions for nocturnal enuresis in children. Cochrane Database of Systematic Reviews. 2013;(7):CD003637. DOI: 10.1002/14651858.CD003637.pub3

[17] Tkaczyk M, Maternik M, Krakowska A, et al. Evaluation of the effect of 3-month bladder basic advice in children with monosymptomatic nocturnal enuresis. Journal of Pediatric Urology. 2017;**13**(6):615.e1-615.e6. DOI: 10.1016/j.jpurol.2017.03.039

[18] Kroll P, Zachwieja J. The system of management nocturnal enuresis based on functional classification. Przegla̧d Lekarski. 2006;**63**:229-232

[19] Butler RJ, Redfern EJ, Holland P. Children's notions about enuresis and the implications for treatment. Scandinavian Journal of Urology and Nephrology. Supplementum. 1994;**163**:39-47

[20] van Dommelen P, Kamphuis M, van Leerdam FJ, et al. The short- and long-term effects of simple behavioral interventions for nocturnal enuresis in young children: A randomized controlled trial. The Journal of Pediatrics. 2009;**154**(5):662-666. DOI: 10.1016/j.jpeds.2008.12.001

[21] Hofmeester I, Kollen BJ, Steffens MG, et al. Predictors for a positive outcome of adapted clinical dry bed training in adolescents and adults with enuresis. Neurourology and Urodynamics. 2016;**35**(8):1006-1010. DOI: 10.1002/nau.22869

[22] Brown ML, Pope AW, Brown EJ. Treatment of primary nocturnal enuresis in children: A review. Child: Care, Health and Development. 2011;**37**(2):153-160. DOI: 10.1111/j.1365-2214.2010.01146.x

[23] Glazener CMA, Evans JHC, Peto RE. Complex behavioural and educational interventions for

nocturnal enuresis in children. Cochrane Database of Systematic Reviews. 2004;(1):CD004668. DOI: 10.1002/14651858.CD004668

[24] van Londen A, van Londen-Barentsen MW, van Son MJ, et al. Arousal training for children suffering from nocturnal enuresis: A 2 1/2 year follow-up. Behaviour Research and Therapy. 1993;**31**(6):613-615

[25] Van Kampen M, Bogaert G, Feys H, et al. High initial efficacy of full-spectrum therapy for nocturnal enuresis in children and adolescents. BJU International. 2002;**90**(1):84-87

[26] Hoekx L, Vermandel A, Wyndaele JJ. Functional bladder capacity after bladder biofeedback predicts long-term outcome in children with nocturnal enuresis. Scandinavian Journal of Urology and Nephrology. 2003;**37**(2):120-123. DOI: 10.1080/00365590310008848

[27] Kajbafzadeh AM, Sharifi-Rad L, Mozafarpour S, et al. Efficacy of transcutaneous interferential electrical stimulation in treatment of children with primary nocturnal enuresis: A randomized clinical trial. Pediatric Nephrology. 2015;**30**(7):1139-1145. DOI: 10.1007/s00467-014-3039-5

[28] Abd El-Moghny SM, El-Din MS, El Shemy SA. Effectiveness of intra-anal biofeedback and electrical stimulation in the treatment of children with refractory monosymptomatic nocturnal enuresis: A comparative randomized controlled trial. International Neurourology Journal. 2018;**22**(4):295-304. DOI: 10.5213/ inj.1836142.071

[29] Glazener CMA, Evans JHC, Peto RE. Alarm interventions for nocturnal enuresis in children. Cochrane Database of Systematic Reviews. 2005;(2):CD002911. DOI: 10.1002/14651858.CD002911.pub2

**69**

*Advances in Treatment of Nocturnal Enuresis in Children*

etiology of primary monosymptomatic enuresis. The Journal of Pediatrics. 2007;**151**(6):571-574. DOI: 10.1016/j.

[38] Rittig S, Schaumburg H, Schmidt F, et al. Long-term home studies of water balance in patients with nocturnal enuresis. Scandinavian Journal of Urology and Nephrology. 1997;**183**:25-26; discussion 26-7

[39] Hamano S, Yamanishi T, Igarashi T, et al. Functional bladder capacity as predictor of response to desmopressin and retention control training in monosymptomatic nocturnal enuresis. European Urology. 2000;**37**(6):718- 722. DOI: 10.1159/000020224

[40] Yeung CK, Sreedhar B, Leung VT,

et al. Ultrasound bladder measurements in patients with primary nocturnal enuresis: A urodynamic and treatment outcome correlation. Journal of Urology.

2004;**6**(Pt 2):2589-2594

[41] Wolfish NM, Barkin J,

Gorodzinsky F, et al. The Canadian enuresis study and evaluation—Shortand long-term safety and efficacy of an oral desmopressin preparation. Scandinavian Journal of Urology and Nephrology. 2003;**37**(1):22-27. DOI: 10.1080/00365590310008631

[42] Caldwell PHY, Sureshkumar P, Wong WCF. Tricyclic and related drugs for nocturnal enuresis in children. Cochrane Database of Systematic Reviews. 2016;(1):CD002117. DOI: 10.1002/14651858.CD002117.pub2

[43] Neveus T. Reboxetine in therapy-resistant enuresis: Results

[37] Glazener CMA, Evans JHC. Desmopressin for nocturnal enuresis in children. Cochrane Database

jpeds.2007.05.024

of Systematic Reviews. 2002;(3):CD002112. DOI: 10.1002/14651858.CD002112

*DOI: http://dx.doi.org/10.5772/intechopen.89106*

[30] Tsuji S, Suruda C, Kimata T, et al. The effect of family assistance to wake children with monosymptomatic enuresis in alarm therapy: A pilot study. The Journal of Urology.

2018;**199**(4):1056-1060. DOI: 10.1016/j.

[31] Apos E, Schuster S, Reece J, et al. Enuresis management in children: Retrospective clinical audit of 2861 cases treated with practitioner-assisted belland-pad alarm. Journal of Pediatrics. 2018;**193**:211-216. DOI: 10.1016/j.

enuresis. Journal of Pediatric Urology.

2018;**14**(5):447.e1-447.e6. DOI: 10.1016/j.jpurol.2018.03.021

[33] Hyuga T, Nakamura S, Kawai S, et al. Evaluation of the effectiveness of a short-term treatment and repeat treatment of nocturnal enuresis using an enuresis alarm. Urology. 2017;**105**:153- 156. DOI: 10.1016/j.urology.2017.01.005

[34] Schulz-Juergensen S, Langguth A, Eggert P. Effect of alarm therapy on conditioning of central reflex control in nocturnal enuresis: Pilot study on changes in prepulse inhibition (PPI). Pediatric Nephrology.

2014;**29**(7):1209-1213. DOI: 10.1007/

[35] Hvistendahl GM, Kamperis K, Rawashdeh YF, et al. The effect of alarm treatment on the functional bladder capacity in children with monosymptomatic nocturnal enuresis.

[36] Schulz-Juergensen S, Rieger M, Schaefer J, et al. Effect of 1-desamino-8-d-arginine vasopressin on prepulse inhibition of startle supports a central

Journal of Urology. 2004;**6**

(Pt 2):2611-2614

s00467-014-2756-0

juro.2017.11.072

jpeds.2017.09.086

[32] Kosilov KV, Geltser BI, Loparev SA, et al. The optimal duration of alarm therapy use in children with primary monosymptomatic nocturnal

*Advances in Treatment of Nocturnal Enuresis in Children DOI: http://dx.doi.org/10.5772/intechopen.89106*

[30] Tsuji S, Suruda C, Kimata T, et al. The effect of family assistance to wake children with monosymptomatic enuresis in alarm therapy: A pilot study. The Journal of Urology. 2018;**199**(4):1056-1060. DOI: 10.1016/j. juro.2017.11.072

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

nocturnal enuresis in children. Cochrane Database of Systematic Reviews. 2004;(1):CD004668. DOI: 10.1002/14651858.CD004668

[24] van Londen A, van Londen-Barentsen MW, van Son MJ, et al. Arousal training for children suffering from nocturnal enuresis: A 2 1/2 year follow-up. Behaviour Research and Therapy. 1993;**31**(6):613-615

[25] Van Kampen M, Bogaert G, Feys H, et al. High initial efficacy of full-spectrum therapy for nocturnal enuresis in children and adolescents. BJU International. 2002;**90**(1):84-87

[26] Hoekx L, Vermandel A, Wyndaele JJ. Functional bladder capacity after bladder biofeedback predicts long-term outcome in children with nocturnal enuresis. Scandinavian Journal of Urology and Nephrology. 2003;**37**(2):120-123. DOI:

10.1080/00365590310008848

10.1007/s00467-014-3039-5

[27] Kajbafzadeh AM, Sharifi-Rad L, Mozafarpour S, et al. Efficacy of transcutaneous interferential electrical stimulation in treatment of children with primary nocturnal enuresis: A randomized clinical trial. Pediatric Nephrology. 2015;**30**(7):1139-1145. DOI:

[28] Abd El-Moghny SM, El-Din MS, El Shemy SA. Effectiveness of intra-anal biofeedback and electrical stimulation in the treatment of children with refractory monosymptomatic nocturnal enuresis: A comparative randomized controlled trial.

International Neurourology Journal. 2018;**22**(4):295-304. DOI: 10.5213/

[29] Glazener CMA, Evans JHC, Peto RE. Alarm interventions for nocturnal enuresis in children. Cochrane Database of Systematic Reviews. 2005;(2):CD002911. DOI: 10.1002/14651858.CD002911.pub2

inj.1836142.071

[16] Caldwell PHY, Nankivell G, Sureshkumar P. Simple behavioural interventions for nocturnal enuresis in children. Cochrane Database of Systematic Reviews. 2013;(7):CD003637. DOI: 10.1002/14651858.CD003637.pub3

[17] Tkaczyk M, Maternik M,

10.1016/j.jpurol.2017.03.039

Lekarski. 2006;**63**:229-232

Krakowska A, et al. Evaluation of the effect of 3-month bladder basic advice in children with monosymptomatic nocturnal enuresis. Journal of Pediatric Urology. 2017;**13**(6):615.e1-615.e6. DOI:

[18] Kroll P, Zachwieja J. The system of management nocturnal enuresis based on functional classification. Przegla̧d

[19] Butler RJ, Redfern EJ, Holland P. Children's notions about enuresis and the implications for treatment. Scandinavian Journal of Urology and Nephrology. Supplementum. 1994;**163**:39-47

[20] van Dommelen P, Kamphuis M, van Leerdam FJ, et al. The short- and long-term effects of simple behavioral interventions for nocturnal enuresis in young children: A randomized controlled trial. The Journal of

Pediatrics. 2009;**154**(5):662-666. DOI:

Development. 2011;**37**(2):153-160. DOI: 10.1111/j.1365-2214.2010.01146.x

[23] Glazener CMA, Evans JHC, Peto RE. Complex behavioural and educational interventions for

10.1016/j.jpeds.2008.12.001

[21] Hofmeester I, Kollen BJ, Steffens MG, et al. Predictors for a positive outcome of adapted clinical dry bed training in adolescents and adults with enuresis. Neurourology and Urodynamics. 2016;**35**(8):1006-1010.

DOI: 10.1002/nau.22869

[22] Brown ML, Pope AW, Brown EJ. Treatment of primary nocturnal enuresis in children: A review. Child: Care, Health and

**68**

[31] Apos E, Schuster S, Reece J, et al. Enuresis management in children: Retrospective clinical audit of 2861 cases treated with practitioner-assisted belland-pad alarm. Journal of Pediatrics. 2018;**193**:211-216. DOI: 10.1016/j. jpeds.2017.09.086

[32] Kosilov KV, Geltser BI, Loparev SA, et al. The optimal duration of alarm therapy use in children with primary monosymptomatic nocturnal enuresis. Journal of Pediatric Urology. 2018;**14**(5):447.e1-447.e6. DOI: 10.1016/j.jpurol.2018.03.021

[33] Hyuga T, Nakamura S, Kawai S, et al. Evaluation of the effectiveness of a short-term treatment and repeat treatment of nocturnal enuresis using an enuresis alarm. Urology. 2017;**105**:153- 156. DOI: 10.1016/j.urology.2017.01.005

[34] Schulz-Juergensen S, Langguth A, Eggert P. Effect of alarm therapy on conditioning of central reflex control in nocturnal enuresis: Pilot study on changes in prepulse inhibition (PPI). Pediatric Nephrology. 2014;**29**(7):1209-1213. DOI: 10.1007/ s00467-014-2756-0

[35] Hvistendahl GM, Kamperis K, Rawashdeh YF, et al. The effect of alarm treatment on the functional bladder capacity in children with monosymptomatic nocturnal enuresis. Journal of Urology. 2004;**6** (Pt 2):2611-2614

[36] Schulz-Juergensen S, Rieger M, Schaefer J, et al. Effect of 1-desamino-8-d-arginine vasopressin on prepulse inhibition of startle supports a central etiology of primary monosymptomatic enuresis. The Journal of Pediatrics. 2007;**151**(6):571-574. DOI: 10.1016/j. jpeds.2007.05.024

[37] Glazener CMA, Evans JHC. Desmopressin for nocturnal enuresis in children. Cochrane Database of Systematic Reviews. 2002;(3):CD002112. DOI: 10.1002/14651858.CD002112

[38] Rittig S, Schaumburg H, Schmidt F, et al. Long-term home studies of water balance in patients with nocturnal enuresis. Scandinavian Journal of Urology and Nephrology. 1997;**183**:25-26; discussion 26-7

[39] Hamano S, Yamanishi T, Igarashi T, et al. Functional bladder capacity as predictor of response to desmopressin and retention control training in monosymptomatic nocturnal enuresis. European Urology. 2000;**37**(6):718- 722. DOI: 10.1159/000020224

[40] Yeung CK, Sreedhar B, Leung VT, et al. Ultrasound bladder measurements in patients with primary nocturnal enuresis: A urodynamic and treatment outcome correlation. Journal of Urology. 2004;**6**(Pt 2):2589-2594

[41] Wolfish NM, Barkin J, Gorodzinsky F, et al. The Canadian enuresis study and evaluation—Shortand long-term safety and efficacy of an oral desmopressin preparation. Scandinavian Journal of Urology and Nephrology. 2003;**37**(1):22-27. DOI: 10.1080/00365590310008631

[42] Caldwell PHY, Sureshkumar P, Wong WCF. Tricyclic and related drugs for nocturnal enuresis in children. Cochrane Database of Systematic Reviews. 2016;(1):CD002117. DOI: 10.1002/14651858.CD002117.pub2

[43] Neveus T. Reboxetine in therapy-resistant enuresis: Results and pathogenetic implications. Scandinavian Journal of Urology and Nephrology. 2006;**40**(1):31-34. DOI: 10.1080/00365590500407803

[44] Lundmark E, Stenberg A, Hagglof B, et al. Reboxetine in therapyresistant enuresis: A randomized placebo-controlled study. Journal of Pediatric Urology. 2016;**12**(6):397.e1-397. e5. DOI: 10.1016/j.jpurol.2016.04.048

[45] Kwak KW, Lee YS, Park KH, et al. Efficacy of desmopressin and enuresis alarm as first and second line treatment for primary monosymptomatic nocturnal enuresis: Prospective randomized crossover study. Journal of Urology. 2010;**184**(6):2521-2526. DOI: 10.1016/j.juro.2010.08.041

[46] Butler RJ, Holland P, Gasson S, et al. Exploring potential mechanisms in alarm treatment for primary nocturnal enuresis. Scandinavian Journal of Urology and Nephrology. 2007;**41**(5):407-413. DOI: 10.1080/00365590701571506

[47] Tempest H, Reynard J, Bryant RJ, et al. Acupuncture in urological practice—A survey of urologists in England. Complementary Therapies in Medicine. 2011;**19**(1):27-31. DOI: 10.1016/j.ctim.2010.10.001

[48] Bjorkstrom G, Hellstrom AL, Andersson S. Electro-acupuncture in the treatment of children with monosymptomatic nocturnal enuresis. Scandinavian Journal of Urology and Nephrology. 2000;**34**(1):21-26

[49] Honjo H, Kawauchi A, Ukimura O, et al. Treatment of monosymptomatic nocturnal enuresis by acupuncture: A preliminary study. International Journal of Urology. 2002;**9**(12):672-676

[50] Huang T, Shu X, Huang YS, et al. Complementary and miscellaneous interventions for nocturnal enuresis in children. Cochrane Database of Systematic Reviews.

2011;(12):CD005230. DOI: 10.1002/14651858.CD005230.pub2

[51] Bower WF, Diao M, Tang JL, et al. Acupuncture for nocturnal enuresis in children: A systematic review and exploration of rationale. Neurourology and Urodynamics. 2005;**24**(3):267-272. DOI: 10.1002/nau.20108

[52] Lv ZT, Song W, Wu J, et al. Efficacy of acupuncture in children with nocturnal enuresis: A systematic review and meta-analysis of randomized controlled trials. Evidence-based Complementary and Alternative Medicine. 2015;**2015**:320701. DOI: 10.1155/2015/320701

[53] Minni B, Capozza N, Creti G, et al. Bladder instability and enuresis treated by acupuncture and electrotherapeutics: Early urodynamic observations. Acupuncture & Electro-Therapeutics Research. 1990;**151**(1):19-25

[54] Yang J, Yang Y, Wang CH, et al. Effect of arginine vasopressin on acupuncture analgesia in the rat. Peptides. 2009;**302**(2):241-247. DOI: 10.1016/j.peptides.2008.10.013

[55] Culbert TP, Banez GA. Wetting the bed: Integrative approaches to nocturnal enuresis. Explore (New York, N.Y.). 2008;**4**(3):215-220. DOI: 10.1016/j. explore.2008.02.014

[56] Sharifi H, Minaie MB, Qasemzadeh MJ, et al. Topical use of *Matricaria recutita* L (chamomile) oil in the treatment of monosymptomatic enuresis in children: A doubleblind randomized controlled trial. Journal Evidence-Based Complementary and Alternative Medicine. 2017;**22**(1):12-17. DOI: 10.1177/2156587215608989

[57] Bartocci C, Lucentini M. Acupuncture and micro-massage in the treatment of idiopathic nocturnal

**71**

*Advances in Treatment of Nocturnal Enuresis in Children*

for treating nocturnal enuresis: Preliminary results of a phase one study. Journal of Pediatric Urology. 2014;**10**(6):1273-1276. DOI: 10.1016/j.

[66] Kuru K, Ansell D, Jones M, et al. Feasibility study of intelligent autonomous determination of the bladder voiding need to treat bedwetting using ultrasound and smartphone ML techniques: Intelligent autonomous treatment of bedwetting. Medical & Biological Engineering & Computing. 2019;**57**(5):1079-1097. DOI:

10.1007/s11517-018-1942-9

jpurol.2014.06.023

*DOI: http://dx.doi.org/10.5772/intechopen.89106*

[58] Yuksek MS, Erdem AF, Atalay C, et al. Acupressure versus oxybutinin

[59] Leboeuf C, Brown P, Herman A, et al. Chiropractic care of children with nocturnal enuresis: A prospective outcome study. Journal of Manipulative

and Physiological Therapeutics.

[61] van Poecke AJ, Cunliffe C. Chiropractic treatment for primary nocturnal enuresis: A case series of 33 consecutive patients. Journal of Manipulative and Physiological Therapeutics. 2009;**32**(8):675-681. DOI:

10.1016/j.jmpt.2009.08.019

[62] Kawauchi A, Tanaka Y, Naito Y, et al. Bladder capacity at the time of enuresis. Urology.

[63] Kim JM, Park JW, Lee CS. Evaluation of nocturnal bladder capacity and nocturnal urine volume in nocturnal enuresis. Journal of Pediatric Urology. 2014;**10**(3):559-563. DOI: 10.1016/j.jpurol.2013.11.020

[64] Borg B, Kamperis K, Olsen LH, et al. Evidence of reduced bladder capacity during nighttime in children with monosymptomatic nocturnal enuresis. Journal of Pediatric Urology. 2018;**14**(2):160.e1-160.e6. DOI: 10.1016/j.jpurol.2017.09.021

[65] Barroso U Jr, Lordelo P, Teles A, et al. New device and new concept

2003;**61**(5):1016-1018

[60] Reed WR, Beavers S, Reddy SK, et al. Chiropractic management of primary nocturnal enuresis. Journal of Manipulative and Physiological Therapeutics. 1994;**17**(9):596-600

1991;**14**(2):110-115

enuresis. Minerva Medica.

in the treatment of enuresis. Journal of International Medical Research. 2003;**31**(6):552-556. DOI: 10.1177/147323000303100611

1981;**72**(33):2237

*Advances in Treatment of Nocturnal Enuresis in Children DOI: http://dx.doi.org/10.5772/intechopen.89106*

enuresis. Minerva Medica. 1981;**72**(33):2237

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

2011;(12):CD005230. DOI: 10.1002/14651858.CD005230.pub2

DOI: 10.1002/nau.20108

10.1155/2015/320701

1990;**151**(1):19-25

explore.2008.02.014

[56] Sharifi H, Minaie MB,

enuresis in children: A doubleblind randomized controlled trial. Journal Evidence-Based Complementary and Alternative Medicine. 2017;**22**(1):12-17. DOI: 10.1177/2156587215608989

[57] Bartocci C, Lucentini M. Acupuncture and micro-massage in the treatment of idiopathic nocturnal

[51] Bower WF, Diao M, Tang JL, et al. Acupuncture for nocturnal enuresis in children: A systematic review and exploration of rationale. Neurourology and Urodynamics. 2005;**24**(3):267-272.

[52] Lv ZT, Song W, Wu J, et al. Efficacy

nocturnal enuresis: A systematic review and meta-analysis of randomized controlled trials. Evidence-based Complementary and Alternative Medicine. 2015;**2015**:320701. DOI:

of acupuncture in children with

[53] Minni B, Capozza N, Creti G, et al. Bladder instability and enuresis treated by acupuncture and electrotherapeutics: Early urodynamic observations. Acupuncture & Electro-Therapeutics Research.

[54] Yang J, Yang Y, Wang CH, et al. Effect of arginine vasopressin on acupuncture analgesia in the rat. Peptides. 2009;**302**(2):241-247. DOI: 10.1016/j.peptides.2008.10.013

[55] Culbert TP, Banez GA. Wetting the bed: Integrative approaches to nocturnal enuresis. Explore (New York, N.Y.). 2008;**4**(3):215-220. DOI: 10.1016/j.

Qasemzadeh MJ, et al. Topical use of *Matricaria recutita* L (chamomile) oil in the treatment of monosymptomatic

and pathogenetic implications. Scandinavian Journal of Urology and Nephrology. 2006;**40**(1):31-34. DOI:

10.1080/00365590500407803

[44] Lundmark E, Stenberg A,

Hagglof B, et al. Reboxetine in therapyresistant enuresis: A randomized placebo-controlled study. Journal of Pediatric Urology. 2016;**12**(6):397.e1-397. e5. DOI: 10.1016/j.jpurol.2016.04.048

[45] Kwak KW, Lee YS, Park KH, et al. Efficacy of desmopressin and enuresis alarm as first and second line treatment

randomized crossover study. Journal of Urology. 2010;**184**(6):2521-2526. DOI:

[46] Butler RJ, Holland P, Gasson S, et al. Exploring potential mechanisms in alarm treatment for primary nocturnal enuresis. Scandinavian Journal of Urology and Nephrology. 2007;**41**(5):407-413. DOI:

[47] Tempest H, Reynard J, Bryant RJ, et al. Acupuncture in urological practice—A survey of urologists in England. Complementary Therapies in Medicine. 2011;**19**(1):27-31. DOI:

for primary monosymptomatic nocturnal enuresis: Prospective

10.1016/j.juro.2010.08.041

10.1080/00365590701571506

10.1016/j.ctim.2010.10.001

[48] Bjorkstrom G, Hellstrom AL, Andersson S. Electro-acupuncture in the treatment of children with monosymptomatic nocturnal enuresis. Scandinavian Journal of Urology and Nephrology. 2000;**34**(1):21-26

[49] Honjo H, Kawauchi A, Ukimura O, et al. Treatment of monosymptomatic nocturnal enuresis by acupuncture: A preliminary study. International Journal

of Urology. 2002;**9**(12):672-676

interventions for nocturnal enuresis in children. Cochrane Database of Systematic Reviews.

[50] Huang T, Shu X, Huang YS, et al. Complementary and miscellaneous

**70**

[58] Yuksek MS, Erdem AF, Atalay C, et al. Acupressure versus oxybutinin in the treatment of enuresis. Journal of International Medical Research. 2003;**31**(6):552-556. DOI: 10.1177/147323000303100611

[59] Leboeuf C, Brown P, Herman A, et al. Chiropractic care of children with nocturnal enuresis: A prospective outcome study. Journal of Manipulative and Physiological Therapeutics. 1991;**14**(2):110-115

[60] Reed WR, Beavers S, Reddy SK, et al. Chiropractic management of primary nocturnal enuresis. Journal of Manipulative and Physiological Therapeutics. 1994;**17**(9):596-600

[61] van Poecke AJ, Cunliffe C. Chiropractic treatment for primary nocturnal enuresis: A case series of 33 consecutive patients. Journal of Manipulative and Physiological Therapeutics. 2009;**32**(8):675-681. DOI: 10.1016/j.jmpt.2009.08.019

[62] Kawauchi A, Tanaka Y, Naito Y, et al. Bladder capacity at the time of enuresis. Urology. 2003;**61**(5):1016-1018

[63] Kim JM, Park JW, Lee CS. Evaluation of nocturnal bladder capacity and nocturnal urine volume in nocturnal enuresis. Journal of Pediatric Urology. 2014;**10**(3):559-563. DOI: 10.1016/j.jpurol.2013.11.020

[64] Borg B, Kamperis K, Olsen LH, et al. Evidence of reduced bladder capacity during nighttime in children with monosymptomatic nocturnal enuresis. Journal of Pediatric Urology. 2018;**14**(2):160.e1-160.e6. DOI: 10.1016/j.jpurol.2017.09.021

[65] Barroso U Jr, Lordelo P, Teles A, et al. New device and new concept

for treating nocturnal enuresis: Preliminary results of a phase one study. Journal of Pediatric Urology. 2014;**10**(6):1273-1276. DOI: 10.1016/j. jpurol.2014.06.023

[66] Kuru K, Ansell D, Jones M, et al. Feasibility study of intelligent autonomous determination of the bladder voiding need to treat bedwetting using ultrasound and smartphone ML techniques: Intelligent autonomous treatment of bedwetting. Medical & Biological Engineering & Computing. 2019;**57**(5):1079-1097. DOI: 10.1007/s11517-018-1942-9

**73**

**Chapter 6**

**Abstract**

**1. Introduction**

Historical Perspective

Urethroplasty

*and Natalia M. Martins*

and Innovations in Penile

*Francisco E. Martins, Pedro Simoes de Oliveira*

physiology, proper patient selection, and reconstructive techniques.

**Keywords:** anterior urethra, urethral stricture, urethroplasty, penile

treatment of penile urethral stricture disease.

Urethral strictures have been common since ancient times. Knowledge was gathered about the treatment of urethral stricture disease by ancient Egyptians and other civilizations more than two millennia ago. Nonetheless, little has changed until about 60 years ago. Since then, the management of urethral strictures, including the penile urethral segment, has been in continuous and rapid evolution. Although various reconstructive techniques are available for the treatment of penile urethral stricture, no single technique has been identified as the method of choice. An understanding of the penile urethral anatomy is important for the diagnosis and

Urethral strictures, in general, are associated with significant impact on patients' quality of life. Penile urethral strictures, in particular, due to their exposed anatomic location and their surgical treatment, may cause significant impact on patients' sexual function and perception of (un)satisfactory penile cosmesis.

Penile urethral strictures are common and impact on quality of life and healthcare costs. Management of penile urethral strictures is complex and depends on the physical characteristics of the stricture. Contemporary studies show no difference between urethral dilation and internal urethrotomy in terms of long-term outcomes. Overall, long-term success rates range from 20 to 30%. However, their recurrence rate is greater for men with longer strictures, penile urethral strictures, multiple strictures, presence of infection, or history of prior procedures, which make them less cost-effective. Surgical urethroplasty is associated with higher long-term success rates, averaging from 85 to 90%, mostly in virgin or noncomplex cases. Historically, modern urethral reconstruction has evolved from 1950s with the revolutionary introduction of Johanson's technique for staged urethral reconstruction. Since then, many techniques have been developed and employed for urethroplasty, depending on the location, length, and character of the stricture. Successful management of urethral strictures requires detailed knowledge of anatomy, patho-

#### **Chapter 6**

## Historical Perspective and Innovations in Penile Urethroplasty

*Francisco E. Martins, Pedro Simoes de Oliveira and Natalia M. Martins*

#### **Abstract**

Penile urethral strictures are common and impact on quality of life and healthcare costs. Management of penile urethral strictures is complex and depends on the physical characteristics of the stricture. Contemporary studies show no difference between urethral dilation and internal urethrotomy in terms of long-term outcomes. Overall, long-term success rates range from 20 to 30%. However, their recurrence rate is greater for men with longer strictures, penile urethral strictures, multiple strictures, presence of infection, or history of prior procedures, which make them less cost-effective. Surgical urethroplasty is associated with higher long-term success rates, averaging from 85 to 90%, mostly in virgin or noncomplex cases. Historically, modern urethral reconstruction has evolved from 1950s with the revolutionary introduction of Johanson's technique for staged urethral reconstruction. Since then, many techniques have been developed and employed for urethroplasty, depending on the location, length, and character of the stricture. Successful management of urethral strictures requires detailed knowledge of anatomy, pathophysiology, proper patient selection, and reconstructive techniques.

**Keywords:** anterior urethra, urethral stricture, urethroplasty, penile

#### **1. Introduction**

Urethral strictures have been common since ancient times. Knowledge was gathered about the treatment of urethral stricture disease by ancient Egyptians and other civilizations more than two millennia ago. Nonetheless, little has changed until about 60 years ago. Since then, the management of urethral strictures, including the penile urethral segment, has been in continuous and rapid evolution. Although various reconstructive techniques are available for the treatment of penile urethral stricture, no single technique has been identified as the method of choice. An understanding of the penile urethral anatomy is important for the diagnosis and treatment of penile urethral stricture disease.

Urethral strictures, in general, are associated with significant impact on patients' quality of life. Penile urethral strictures, in particular, due to their exposed anatomic location and their surgical treatment, may cause significant impact on patients' sexual function and perception of (un)satisfactory penile cosmesis.

The anatomical and physical characteristics of the penile urethra are associated with additional challenges when compared to other urethral locations, especially due to its unsuitability for anastomotic repair and its relatively thinner corpus spongiosum. The choice of penile urethroplasty technique is largely influenced by etiology, location, length of the stricture, as well as prior surgical treatments. There are a number of challenges and controversies in the surgical reconstruction of penile urethral strictures, such as the use of grafts vs. flaps, use of skin vs. oral mucosa graft (OMG) tissue for augmentation or substitution techniques, the most appropriate indications for a single or a staged (at times, multiple) reconstruction, and, lastly, the management of particularly complex cases such as panurethral stricture disease and hypospadias "cripples" to achieve the best possible outcome.

Although penile urethral strictures can be managed by any of the abovementioned procedures individually, they can also be more adequately treated by a combined approach. Among the various procedures available for treating urethral stricture, one-stage buccal mucosal graft urethroplasty is the current standard practice. The selection of technique for penile urethroplasty for an individual patient largely depends not only on the expertise of the surgeon but also upon the stricture's etiology, pathological characteristics, and location. Therefore, contemporary reconstructive urologists working in this field should be aware of, and permanently keep themselves updated on, the numerous surgical techniques required to deal with any condition of the urethra that might surface at the time of surgery.

This review provides a brief update of the options for the surgical reconstruction of different types and sites of penile urethral stricture as well as discussing current controversies, innovations, and possible future research in urethral reconstruction of the penile urethra.

#### **2. Anatomical considerations**

Classically, the anterior urethra is divided, at the level of the penoscrotal junction inferiorly and the suspensory ligament superiorly, into bulbar and penile segments, the penile part consisting of the external meatus, fossa navicularis, and the penile shaft urethra. The penile urethra extends from the distal margin of the bulbospongiosus (or penoscrotal junction) to the external meatus. The bulbar (proximal) segment is the shorter of the two and is located in the midline between both the penile crural and the cavernosal bodies. The penile urethra (distal segment of the anterior urethra), also called pendulous, lies in a dorsal groove between the two corpora cavernosa and extends from the penoscrotal junction to the tip of the glans penis. It is surrounded in its full length by the corpus spongiosum; it is mobile and stretches during penile erection; and its length varies according to the penile length. The caliber of the anterior urethral lumen is relatively uniform, widening distally to form the fossa navicularis, and narrowing again to end at the external meatus (**Figure 1**).

Histologically, the penile (distal anterior) urethra is surrounded by five tissue layers: urethral epithelium and lamina propria (urethral mucosa), corpus spongiosum, tunica albuginea, and Buck's fascia [1]. Most of the penile shaft urethra is lined by a stratified and pseudostratified columnar epithelium, except for the distal penile urethra, including the fossa navicularis, which is lined by ciliated stratified columnar epithelium or stratified nonkeratinizing squamous epithelium. The lamina propria of the penile urethra is a fibroconnective tissue with elastic fibers and scattered, longitudinally oriented smooth muscle fibers. Multiple mucussecreting glands drain into the anterior urethral lumen, known as Cowper's glands in the bulbar urethra and Littre's glands in the penile urethra.

**75**

**Figure 2.**

*blood drainage.*

**Figure 1.**

*Historical Perspective and Innovations in Penile Urethroplasty*

The anterior urethra obtains its blood supply from the first of three penile branches of the internal pudendal artery, which in turn is a branch of the internal iliac artery. The internal pudendal artery travels through the Alcock canal and gives the inferior rectal artery, posterior scrotal artery and perineal artery, and then terminates as the common penile artery. Three branches arise from the common penile artery: the paired urethral or, most commonly, bulbourethral arteries that pierce the perineal body at a posterolateral location and supply the urethra, spongiosum, and the glans. The other branches are the paired cavernosal arteries that pierce the penile hilum to travel in the center of the erectile tissue, and the deep dorsal penile artery that travel between the crura and beneath the pubic bone to run under the Buck's fascia sending multiple circumflex branches to the corpus spongiosum and terminal branches to the glans penis, thus providing in a retrograde fashion a dual blood supply to the corpus spongiosum and urethra. It also sends cavernosal branches to contribute to the hemodynamics of the erection (**Figure 2A** and **B**). The venous

*Schematic illustration of vascularization of the penis and urethra: (A) arterial blood supply and (B) venous* 

*pubourethral ligaments (reproduced with permission from Dr. Enzo Palminteri).*

*Sagittal sectional view of the male urethra. The areas in blue and yellow represent the corpus spongiosum and lumen of the anterior urethra, respectively. The penile urethra extends distally from the penoscrotal junction or* 

*DOI: http://dx.doi.org/10.5772/intechopen.85908*

*Historical Perspective and Innovations in Penile Urethroplasty DOI: http://dx.doi.org/10.5772/intechopen.85908*

#### **Figure 1.**

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

condition of the urethra that might surface at the time of surgery.

of the penile urethra.

meatus (**Figure 1**).

**2. Anatomical considerations**

This review provides a brief update of the options for the surgical reconstruction of different types and sites of penile urethral stricture as well as discussing current controversies, innovations, and possible future research in urethral reconstruction

Classically, the anterior urethra is divided, at the level of the penoscrotal junction inferiorly and the suspensory ligament superiorly, into bulbar and penile segments, the penile part consisting of the external meatus, fossa navicularis, and the penile shaft urethra. The penile urethra extends from the distal margin of the bulbospongiosus (or penoscrotal junction) to the external meatus. The bulbar (proximal) segment is the shorter of the two and is located in the midline between both the penile crural and the cavernosal bodies. The penile urethra (distal segment of the anterior urethra), also called pendulous, lies in a dorsal groove between the two corpora cavernosa and extends from the penoscrotal junction to the tip of the glans penis. It is surrounded in its full length by the corpus spongiosum; it is mobile and stretches during penile erection; and its length varies according to the penile length. The caliber of the anterior urethral lumen is relatively uniform, widening distally to form the fossa navicularis, and narrowing again to end at the external

Histologically, the penile (distal anterior) urethra is surrounded by five tissue layers: urethral epithelium and lamina propria (urethral mucosa), corpus spongiosum, tunica albuginea, and Buck's fascia [1]. Most of the penile shaft urethra is lined by a stratified and pseudostratified columnar epithelium, except for the distal penile urethra, including the fossa navicularis, which is lined by ciliated stratified columnar epithelium or stratified nonkeratinizing squamous epithelium. The lamina propria of the penile urethra is a fibroconnective tissue with elastic fibers and scattered, longitudinally oriented smooth muscle fibers. Multiple mucussecreting glands drain into the anterior urethral lumen, known as Cowper's glands

in the bulbar urethra and Littre's glands in the penile urethra.

The anatomical and physical characteristics of the penile urethra are associated with additional challenges when compared to other urethral locations, especially due to its unsuitability for anastomotic repair and its relatively thinner corpus spongiosum. The choice of penile urethroplasty technique is largely influenced by etiology, location, length of the stricture, as well as prior surgical treatments. There are a number of challenges and controversies in the surgical reconstruction of penile urethral strictures, such as the use of grafts vs. flaps, use of skin vs. oral mucosa graft (OMG) tissue for augmentation or substitution techniques, the most appropriate indications for a single or a staged (at times, multiple) reconstruction, and, lastly, the management of particularly complex cases such as panurethral stricture disease and hypospadias "cripples" to achieve the best possible outcome. Although penile urethral strictures can be managed by any of the abovementioned procedures individually, they can also be more adequately treated by a combined approach. Among the various procedures available for treating urethral stricture, one-stage buccal mucosal graft urethroplasty is the current standard practice. The selection of technique for penile urethroplasty for an individual patient largely depends not only on the expertise of the surgeon but also upon the stricture's etiology, pathological characteristics, and location. Therefore, contemporary reconstructive urologists working in this field should be aware of, and permanently keep themselves updated on, the numerous surgical techniques required to deal with any

**74**

*Sagittal sectional view of the male urethra. The areas in blue and yellow represent the corpus spongiosum and lumen of the anterior urethra, respectively. The penile urethra extends distally from the penoscrotal junction or pubourethral ligaments (reproduced with permission from Dr. Enzo Palminteri).*

The anterior urethra obtains its blood supply from the first of three penile branches of the internal pudendal artery, which in turn is a branch of the internal iliac artery. The internal pudendal artery travels through the Alcock canal and gives the inferior rectal artery, posterior scrotal artery and perineal artery, and then terminates as the common penile artery. Three branches arise from the common penile artery: the paired urethral or, most commonly, bulbourethral arteries that pierce the perineal body at a posterolateral location and supply the urethra, spongiosum, and the glans. The other branches are the paired cavernosal arteries that pierce the penile hilum to travel in the center of the erectile tissue, and the deep dorsal penile artery that travel between the crura and beneath the pubic bone to run under the Buck's fascia sending multiple circumflex branches to the corpus spongiosum and terminal branches to the glans penis, thus providing in a retrograde fashion a dual blood supply to the corpus spongiosum and urethra. It also sends cavernosal branches to contribute to the hemodynamics of the erection (**Figure 2A** and **B**). The venous

#### **Figure 2.**

*Schematic illustration of vascularization of the penis and urethra: (A) arterial blood supply and (B) venous blood drainage.*

drainage is through the emissary veins into the circumflex branches of the deep dorsal penile vein as well as through the urethral and bulbar veins into the internal pudendal vein. The anterior urethra is innervated by the urethrobulbar nerve, a branch of the perineal nerve derived from the pudendal nerve. The bulbocavernosus nerve, which is a branch of the pudendal nerve, gives off two branches that penetrate the rhabdosphincter at the three and nine o'clock positions. The pudendal nerve, gathering fibers from the second, third and fourth sacral spinal nerve, is both motor to the urethral rhabdosphincter and sensory to the urethra and glans penis (**Figure 3**). The lymphatic drainage of the anterior urethra is via the superficial and deep inguinal nodes, whereas the lymphatic drainage of the more proximal (the bulbar, membranous, and prostatic) urethra can take three routes: to the external iliac nodes, to the obturator and internal iliac nodes, or to the presacral nodes [2].

Understanding the penile anatomy and, in particular, the penile skin arterial blood supply is an important resource for penile urethral surgical reconstruction. The penis is covered with an elastic layer of skin that has no subcuticular adipose tissue: the dartos fascia, a layer of loose areolar subcutaneous connective tissue in the penis and scrotum. It lies immediately beneath the penile skin, allowing the skin to move freely over the shaft of the penis and is contiguous with Colles fascia in the perineum. The dartos, also with no adipose tissue, slides freely over the underlying Buck's fascia and is an extension of Scarpa's fascia of the abdominal wall, carrying superficial nerves, lymphatics, and blood vessels, which make this fascia extremely useful in bringing blood supply and preventing fistulation in urethral reconstruction. Beneath the dartos fascia lies the Buck's fascia, which surrounds the tunica albuginea of the two corpora cavernosa and the corpus spongiosum.

The development of fasciocutaneous penile skin island flaps, either as a vertical flap (as in Orandi flap) or as a circular transverse flap (as in McAninch/Quartey flap), takes advantage of the natural anatomical, relatively avascular cleavage planes between the skin and the dartos fascia and another between the dartos fascia and Buck's fascia.

The blood supply to the penile skin and anterior scrotal wall comes from the external pudendal arteries, whereas the inferior and posterior aspect of the scrotum

#### **Figure 3.**

*Schematic illustration of autonomic and somatic innervation of the penis and urethra (reproduced with permission from Dr. Enzo Palminteri).*

**77**

**Figure 4.**

strictures.

*Historical Perspective and Innovations in Penile Urethroplasty*

the penis is primarily to the superficial inguinal nodes.

derives its blood supply from the posterior scrotal arteries, which are branches of the perineal artery, which in turn is a further branch of the internal pudendal artery (**Figure 4**). The superficial/superior branches of the external pudendal artery travel from medially and across the femoral triangle and within Scarpa's fascia to enter the base of the penis. After giving off anterior scrotal branches, they arborize to form an arterial network within the dartos fascia. Also, at the base of the penis, branches from the axial penile artery form a subdermal plexus to supply the distal penile skin and prepuce. Because the communicating vessels between the subcutaneous and subdermal arterial plexuses are minimal, a relatively avascular plane can be developed between the dartos and Buck's fascia. This fascial plexus, that is considered axial, is the true blood supply to the penile island skin flaps used in urethroplasty and, therefore, they can be mobilized widely and transposed aggressively and reliably. The venous drainage of the penis includes the superficial dorsal vein, the deep dorsal vein, and the crural veins. The superficial dorsal vein drains the skin of the penis and empties into the superficial external pudendal vein and then into the saphenous vein. The deep dorsal vein begins at the base of the glans and retro coronal area and then travels deep to the Buck's fascia between the paired deep dorsal arteries. Along its course, it receives circumflex veins from the spongiosum until it passes under the pubic bone to join the periprostatic venous complex. The cavernosal veins drain into a subtunical venous plexus; then through emissary veins, they join the circumflex veins, which in turn empty into the crural vein and the periprostatic plexus or the internal pudendal veins. The lymphatic drainage of

A detailed understanding of the anatomy of the anterior urethra is a critical prerequisite for the accurate diagnosis and successful management of urethral

*Schematic illustration of the superficial arterial supply and venous drainage of the penis and scrotum.*

*DOI: http://dx.doi.org/10.5772/intechopen.85908*

#### *Historical Perspective and Innovations in Penile Urethroplasty DOI: http://dx.doi.org/10.5772/intechopen.85908*

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

drainage is through the emissary veins into the circumflex branches of the deep dorsal penile vein as well as through the urethral and bulbar veins into the internal pudendal vein. The anterior urethra is innervated by the urethrobulbar nerve, a branch of the perineal nerve derived from the pudendal nerve. The bulbocavernosus nerve, which is a branch of the pudendal nerve, gives off two branches that penetrate the rhabdosphincter at the three and nine o'clock positions. The pudendal nerve, gathering fibers from the second, third and fourth sacral spinal nerve, is both motor to the urethral rhabdosphincter and sensory to the urethra and glans penis (**Figure 3**). The lymphatic drainage of the anterior urethra is via the superficial and deep inguinal nodes, whereas the lymphatic drainage of the more proximal (the bulbar, membranous, and prostatic) urethra can take three routes: to the external iliac nodes, to the obturator and internal iliac nodes, or to the presacral nodes [2]. Understanding the penile anatomy and, in particular, the penile skin arterial blood supply is an important resource for penile urethral surgical reconstruction. The penis is covered with an elastic layer of skin that has no subcuticular adipose tissue: the dartos fascia, a layer of loose areolar subcutaneous connective tissue in the penis and scrotum. It lies immediately beneath the penile skin, allowing the skin to move freely over the shaft of the penis and is contiguous with Colles fascia in the perineum. The dartos, also with no adipose tissue, slides freely over the underlying Buck's fascia and is an extension of Scarpa's fascia of the abdominal wall, carrying superficial nerves, lymphatics, and blood vessels, which make this fascia extremely useful in bringing blood supply and preventing fistulation in urethral reconstruction. Beneath the dartos fascia lies the Buck's fascia, which surrounds the tunica

albuginea of the two corpora cavernosa and the corpus spongiosum.

The development of fasciocutaneous penile skin island flaps, either as a vertical flap (as in Orandi flap) or as a circular transverse flap (as in McAninch/Quartey flap), takes advantage of the natural anatomical, relatively avascular cleavage planes between the skin and the dartos fascia and another between the dartos fascia and Buck's fascia. The blood supply to the penile skin and anterior scrotal wall comes from the external pudendal arteries, whereas the inferior and posterior aspect of the scrotum

*Schematic illustration of autonomic and somatic innervation of the penis and urethra (reproduced with* 

**76**

**Figure 3.**

*permission from Dr. Enzo Palminteri).*

derives its blood supply from the posterior scrotal arteries, which are branches of the perineal artery, which in turn is a further branch of the internal pudendal artery (**Figure 4**). The superficial/superior branches of the external pudendal artery travel from medially and across the femoral triangle and within Scarpa's fascia to enter the base of the penis. After giving off anterior scrotal branches, they arborize to form an arterial network within the dartos fascia. Also, at the base of the penis, branches from the axial penile artery form a subdermal plexus to supply the distal penile skin and prepuce. Because the communicating vessels between the subcutaneous and subdermal arterial plexuses are minimal, a relatively avascular plane can be developed between the dartos and Buck's fascia. This fascial plexus, that is considered axial, is the true blood supply to the penile island skin flaps used in urethroplasty and, therefore, they can be mobilized widely and transposed aggressively and reliably.

The venous drainage of the penis includes the superficial dorsal vein, the deep dorsal vein, and the crural veins. The superficial dorsal vein drains the skin of the penis and empties into the superficial external pudendal vein and then into the saphenous vein. The deep dorsal vein begins at the base of the glans and retro coronal area and then travels deep to the Buck's fascia between the paired deep dorsal arteries. Along its course, it receives circumflex veins from the spongiosum until it passes under the pubic bone to join the periprostatic venous complex. The cavernosal veins drain into a subtunical venous plexus; then through emissary veins, they join the circumflex veins, which in turn empty into the crural vein and the periprostatic plexus or the internal pudendal veins. The lymphatic drainage of the penis is primarily to the superficial inguinal nodes.

A detailed understanding of the anatomy of the anterior urethra is a critical prerequisite for the accurate diagnosis and successful management of urethral strictures.

### **3. Etiology**

The etiology of contemporary urethral stricture disease involves a traumatic, iatrogenic, inflammatory, and idiopathic origin [3, 4]. Pathophysiology differs with age. The major causes of anterior urethral stricture in children are more likely to be trauma, mainly straddle injury, and complications from hypospadias surgery. Congenital and idiopathic strictures may also occur in children. In adult patients, most urethral strictures have an iatrogenic origin, mainly traumatic catheterization or transurethral manipulation or instrumentation. In the <10-year-old age group, strictures are mainly localized in the penile urethra, whereas in the >10-year-old age group, the bulbar urethra is the most common location [5].

In the past, inflammatory urethral strictures were predominantly associated with gonococcal urethritis, which has been effectively eradicated with penicillinbased antimicrobial agents. However, the emergence of resistant strains of *Neisseria gonorrhoeae* may be responsible for resurgence in these cases. Lichen sclerosus (LS, also and erroneously known as balanitis xerotica obliterans) is another inflammatory and challenging cause of urethral stricture disease, which usually involves genital skin, often progressing to panurethral stricture disease, and is associated with comorbidities, such as diabetes and obesity, which may aggravate surgical treatment [6, 7].

Stricture etiology is of particular significance in the penile urethra, as they tend to be more diffuse in nature (averaging 6.1 cm), especially if associated with LS, and shorter in the bulbar urethra (averaging 3.1 cm). Urethral strictures can be classified by their most common urethral location. Strictures involving the external meatus and fossa navicularis are predominantly inflammatory and iatrogenic in origin in 33–47% [3]. In the series reported by Fenton et al., globally, the etiology of anterior urethral strictures was idiopathic in 34%, iatrogenic in 32%, inflammatory in 20%, and traumatic in 14% [3].

Iatrogenic strictures are typically associated with instrumentation, such as transurethral resection, prolonged catheterization, and cystoscopy, totaling 90% of all penile strictures. Prior hypospadias repair and radical prostatectomy contributed to 6.3 and 3.2%, respectively [3, 8]. Such strictures are mainly the result of an ischemic injury secondary to traumatic urethral manipulation or instrumentation, particularly when a large bore catheter or resectoscope is used. Therefore, whenever relatively prolonged catheterization is necessary, smaller caliber/Fr catheters are recommended. For more extended periods of time, a suprapubic catheter is a better option.

Malignant strictures should be approached in a different clinical context and most likely require mutilating radical surgery.


**79**

*Historical Perspective and Innovations in Penile Urethroplasty*

*Clinical evaluation:* the diagnosis of penile urethral strictures, like any other type of stricture, regardless of location, is based on a suggestive clinical history and physical examination. The main symptoms are related to obstructive voiding or urinary tract infection, or both. Some patients may less often present with urinary retention. Weak stream, incomplete bladder emptying, and a hyperactive bladder are usually the most prevalent complaints of patients with anterior urethral stricture [9]. If questioned carefully, most patients who present in chronic retention may state that their symptoms have been present for a long time, which they have tolerated fairly well and, therefore, have been neglected. In some occasions, the diagnosis is brought up to the urologist's attention because of difficult urethral catheterization for any reason, often in the operating theater before an operation that requires routine urethral catheterization. In about 1.3%, renal failure is the

Any relevant past history of urethral instrumentation, hypospadias surgery, and genital trauma should be obtained. Obstructive voiding symptoms should be assessed with a validated questionnaire. Presence of risk factors and comorbidities that may provoke ischemia or impair wound healing should be probed for. These include obesity, diabetes mellitus, severe peripheral vascular disease, cigarette smoking, long-distance bicycle riding, horseback riding, and sexually transmitted infections. Physical examination should include palpation of the penile shaft for nodules or dense urethral scarring or constriction. The urethral meatus should be examined for narrowing and the surrounding glans for signs of LS. The penis should be examined to assess whether the patient has been circumcised, or there is sufficient shaft skin to allow development of a penile skin flap. The bladder should be assessed for potential detrusor hypocontractility, distention, and presence of an abdominal

*Uroflowmetry:* this test provides a quantitative estimate of the severity of obstruction. A flattened, "en plateau" voiding pattern along with elevated postvoid residual urine volume signals the degree of urethral narrowing and efficiency of voiding and bladder emptying (**Figure 5**). More formal urodynamic studies (pressure-flow studies) are rarely indicated or necessary, except for complex cases or when the anatomic location of obstruction is needed in presence of concomitant

*Radiographic contrast studies:* contrast studies of the urethra are the cornerstone of the imaging diagnosis. The combination of dynamic retrograde urethrogram and voiding cystourethrogram allows accurate assessment of stricture length and location (**Figure 6**). Dynamic retrograde urethrogram has been rated the gold standard of urethral stricture evaluation with a specificity and sensitivity of 90% [10]. *Ultrasonography/sonourethrography:* ultrasonography has a limited role in the evaluation of the male urethra. It may be useful to detect concomitant lesions such as calculus, trauma-induced soft tissue injury, or Peyronie's plaques that may coexist with urethral stricture disease. Sonourethrography, introduced in the mid-1980s, was reported to be a more accurate tool for the diagnosis and characterization of strictures, particularly in the bulbar urethra [11]. In addition to providing accurate information of the urethral stricture characteristics, sonourethrography allows assessment of the health and integrity of the soft tissues surrounding the strictured urethra. This modality represents an adjunct to contrast-enhanced studies and can increase the accuracy of anterior stricture length and spongiofibrosis as well as the inner diameter of the urethral lumen and, thus, improve surgical planning [12].

*Endoscopy:* endoscopic evaluation of a urethral stricture has a limited role as it allows only the identification of the most distal portion of the urethra. It does not determine

*DOI: http://dx.doi.org/10.5772/intechopen.85908*

initial presentation of a urethral stricture [9].

scar from a previous suprapubic cystostomy.

prostatic obstruction.

**4. Diagnostic evaluation**

#### **Table 1.**

*Management options for penile urethral strictures.*

#### **4. Diagnostic evaluation**

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

The etiology of contemporary urethral stricture disease involves a traumatic, iatrogenic, inflammatory, and idiopathic origin [3, 4]. Pathophysiology differs with age. The major causes of anterior urethral stricture in children are more likely to be trauma, mainly straddle injury, and complications from hypospadias surgery. Congenital and idiopathic strictures may also occur in children. In adult patients, most urethral strictures have an iatrogenic origin, mainly traumatic catheterization or transurethral manipulation or instrumentation. In the <10-year-old age group, strictures are mainly localized in the penile urethra, whereas in the >10-year-old age group, the bulbar urethra is the most common

In the past, inflammatory urethral strictures were predominantly associated with gonococcal urethritis, which has been effectively eradicated with penicillinbased antimicrobial agents. However, the emergence of resistant strains of

*Neisseria gonorrhoeae* may be responsible for resurgence in these cases. Lichen sclerosus (LS, also and erroneously known as balanitis xerotica obliterans) is another inflammatory and challenging cause of urethral stricture disease, which usually involves genital skin, often progressing to panurethral stricture disease, and is associated with comorbidities, such as diabetes and obesity, which may aggravate

Stricture etiology is of particular significance in the penile urethra, as they tend to be more diffuse in nature (averaging 6.1 cm), especially if associated with LS, and shorter in the bulbar urethra (averaging 3.1 cm). Urethral strictures can be classified by their most common urethral location. Strictures involving the external meatus and fossa navicularis are predominantly inflammatory and iatrogenic in origin in 33–47% [3]. In the series reported by Fenton et al., globally, the etiology of anterior urethral strictures was idiopathic in 34%, iatrogenic in 32%, inflammatory

Iatrogenic strictures are typically associated with instrumentation, such as transurethral resection, prolonged catheterization, and cystoscopy, totaling 90% of all penile strictures. Prior hypospadias repair and radical prostatectomy contributed to 6.3 and 3.2%, respectively [3, 8]. Such strictures are mainly the result of an ischemic injury secondary to traumatic urethral manipulation or instrumentation, particularly when a large bore catheter or resectoscope is used. Therefore, whenever relatively prolonged catheterization is necessary, smaller caliber/Fr catheters are recommended. For more extended periods of time, a suprapubic catheter is a better option. Malignant strictures should be approached in a different clinical context and

**3. Etiology**

location [5].

surgical treatment [6, 7].

in 20%, and traumatic in 14% [3].

Urethral dilatation Internal urethrotomy Laser urethrotomy

Combination of grafts and flaps One-stage urethroplasty Staged urethroplasty

*Management options for penile urethral strictures.*

Grafts Flaps

most likely require mutilating radical surgery.

**78**

**Table 1.**

*Clinical evaluation:* the diagnosis of penile urethral strictures, like any other type of stricture, regardless of location, is based on a suggestive clinical history and physical examination. The main symptoms are related to obstructive voiding or urinary tract infection, or both. Some patients may less often present with urinary retention. Weak stream, incomplete bladder emptying, and a hyperactive bladder are usually the most prevalent complaints of patients with anterior urethral stricture [9]. If questioned carefully, most patients who present in chronic retention may state that their symptoms have been present for a long time, which they have tolerated fairly well and, therefore, have been neglected. In some occasions, the diagnosis is brought up to the urologist's attention because of difficult urethral catheterization for any reason, often in the operating theater before an operation that requires routine urethral catheterization. In about 1.3%, renal failure is the initial presentation of a urethral stricture [9].

Any relevant past history of urethral instrumentation, hypospadias surgery, and genital trauma should be obtained. Obstructive voiding symptoms should be assessed with a validated questionnaire. Presence of risk factors and comorbidities that may provoke ischemia or impair wound healing should be probed for. These include obesity, diabetes mellitus, severe peripheral vascular disease, cigarette smoking, long-distance bicycle riding, horseback riding, and sexually transmitted infections.

Physical examination should include palpation of the penile shaft for nodules or dense urethral scarring or constriction. The urethral meatus should be examined for narrowing and the surrounding glans for signs of LS. The penis should be examined to assess whether the patient has been circumcised, or there is sufficient shaft skin to allow development of a penile skin flap. The bladder should be assessed for potential detrusor hypocontractility, distention, and presence of an abdominal scar from a previous suprapubic cystostomy.

*Uroflowmetry:* this test provides a quantitative estimate of the severity of obstruction. A flattened, "en plateau" voiding pattern along with elevated postvoid residual urine volume signals the degree of urethral narrowing and efficiency of voiding and bladder emptying (**Figure 5**). More formal urodynamic studies (pressure-flow studies) are rarely indicated or necessary, except for complex cases or when the anatomic location of obstruction is needed in presence of concomitant prostatic obstruction.

*Radiographic contrast studies:* contrast studies of the urethra are the cornerstone of the imaging diagnosis. The combination of dynamic retrograde urethrogram and voiding cystourethrogram allows accurate assessment of stricture length and location (**Figure 6**). Dynamic retrograde urethrogram has been rated the gold standard of urethral stricture evaluation with a specificity and sensitivity of 90% [10].

*Ultrasonography/sonourethrography:* ultrasonography has a limited role in the evaluation of the male urethra. It may be useful to detect concomitant lesions such as calculus, trauma-induced soft tissue injury, or Peyronie's plaques that may coexist with urethral stricture disease. Sonourethrography, introduced in the mid-1980s, was reported to be a more accurate tool for the diagnosis and characterization of strictures, particularly in the bulbar urethra [11]. In addition to providing accurate information of the urethral stricture characteristics, sonourethrography allows assessment of the health and integrity of the soft tissues surrounding the strictured urethra. This modality represents an adjunct to contrast-enhanced studies and can increase the accuracy of anterior stricture length and spongiofibrosis as well as the inner diameter of the urethral lumen and, thus, improve surgical planning [12].

*Endoscopy:* endoscopic evaluation of a urethral stricture has a limited role as it allows only the identification of the most distal portion of the urethra. It does not determine

#### *Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

#### **Figure 5.**

*"En plateau" obstructive uroflow in a patient with anterior urethral stricture.*

the length of the stricture nor can it assess the proximal stricture extremity and the corresponding proximal urethra. However, it may help to determine the amount of distal urethral elasticity, or when the insertion of a guide-wire through the stricture is necessary or deemed safe, or in a rare case of suspicion of urethral carcinoma.

**81**

*Historical Perspective and Innovations in Penile Urethroplasty*

**5. Preoperative planning and intraoperative decision-making**

Any appropriate treatment plan needs accurate identification of the stricture characteristics: location, length, depth, and thickness of fibrotic tissue (spongiofibrosis). It is critical that both the proximal and distal ends of a urethral stricture are completely and accurately assessed with endoscopy and bougienage during reconstruction as to not miss any diseased segment of the urethra. Both patient and urethral reconstructive surgeons must understand completely the goal(s) of treatment before a decision is made. The decision to choose urethroplasty over another approach to a specific urethral stricture depends on patient expectations, goals, and comorbidities. In elderly or frail patients, an expectant or conservative management is more likely to be offered. Therefore, treatment options and their individual potential outcomes in terms of cure, or simply palliation, and complications should be carefully discussed with the patients and their family. On the other hand, urethral reconstructive surgeons need to keep themselves updated and abreast regarding the vast array of treatment options and their precise and specific indications and, therefore, should be flexible enough to intraoperatively adapt and/or adopt a different strategy for a specific scenario, which was not anticipated preoperatively. Thus, it is only legitimate and ethical to embark on urethral reconstruction if one can master and offer the patient all necessary surgical options to treat his specific urethral problem. It is very important to bear in mind that the penile urethra is the most exposed segment of the male urethra, and any surgical procedure or technique should achieve not only a satisfactory functional outcome but also a cosmetic one.

The key techniques include mainly urethral dilatation, endoscopic urethrotomy, anastomotic repairs (rarely in the penile urethra), substitution repairs (ventral, dorsal, double-faced), free grafts of skin (full thickness and split thickness skin), oral mucosa, lingual mucosa, bladder mucosa, retroauricular skin (Wolf's graft), and skin flap repairs (circumferential, longitudinal and variants) from penile and (less commonly) scrotal skin, as well as the use of adjunctive maneuvers such as the use of advancement flaps for additional blood supply or defect coverage (**Table 1**). **Urethral dilatation:** several methods for urethral dilatation exist: dilatation with a balloon, filiform and followers, urethral sounds (metallic or nonmetallic), or self-catheter dilatation. Urethral dilatation is carried out by gradual progressive stretching of the urethral lumen to a maximal diameter of 24 Fr. However, if performed aggressively, it will lead to further urethral trauma and scarring. It should be regarded as a palliative procedure and rarely as a curative one. It is mainly indicated in very select cases of strictures of the external meatus and fossa navicularis. It should be avoided in patients with LS as it often worsens the inflammatory process. Repeat dilatation should be avoided as it does not treat the underlying

**Internal urethrotomy:** also called direct vision internal urethrotomy (DVIU), it was first described by Sachse [13]. It consists of a cold-knife incision of the scar tissue allowing its release and healing of the underlying tissue by secondary epithelialization around a urethral catheter and thereby increasing the diameter of the urethral lumen. Apparently, only superficial strictures benefit from this treatment option when the incision is carried out through all thickness of the scar. Its success depends mostly on stricture length and degree of spongiofibrosis [14, 15]. It is best indicated for short strictures (<1.5 cm in length). Heyns et al. have suggested that if the stricture has not recurred within the first 3 months after a single DVIU (or dilatation), the stricture-free

dense spongiofibrosis associated with more complex strictures.

*DOI: http://dx.doi.org/10.5772/intechopen.85908*

**6. Management options**

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

*"En plateau" obstructive uroflow in a patient with anterior urethral stricture.*

the length of the stricture nor can it assess the proximal stricture extremity and the corresponding proximal urethra. However, it may help to determine the amount of distal urethral elasticity, or when the insertion of a guide-wire through the stricture is

*Retrograde urethrogram of long, irregular, "saw-toothed" penile urethral stricture typical of lichen sclerosus.*

necessary or deemed safe, or in a rare case of suspicion of urethral carcinoma.

**80**

**Figure 6.**

**Figure 5.**

#### **5. Preoperative planning and intraoperative decision-making**

Any appropriate treatment plan needs accurate identification of the stricture characteristics: location, length, depth, and thickness of fibrotic tissue (spongiofibrosis). It is critical that both the proximal and distal ends of a urethral stricture are completely and accurately assessed with endoscopy and bougienage during reconstruction as to not miss any diseased segment of the urethra. Both patient and urethral reconstructive surgeons must understand completely the goal(s) of treatment before a decision is made. The decision to choose urethroplasty over another approach to a specific urethral stricture depends on patient expectations, goals, and comorbidities. In elderly or frail patients, an expectant or conservative management is more likely to be offered. Therefore, treatment options and their individual potential outcomes in terms of cure, or simply palliation, and complications should be carefully discussed with the patients and their family. On the other hand, urethral reconstructive surgeons need to keep themselves updated and abreast regarding the vast array of treatment options and their precise and specific indications and, therefore, should be flexible enough to intraoperatively adapt and/or adopt a different strategy for a specific scenario, which was not anticipated preoperatively. Thus, it is only legitimate and ethical to embark on urethral reconstruction if one can master and offer the patient all necessary surgical options to treat his specific urethral problem. It is very important to bear in mind that the penile urethra is the most exposed segment of the male urethra, and any surgical procedure or technique should achieve not only a satisfactory functional outcome but also a cosmetic one.

#### **6. Management options**

The key techniques include mainly urethral dilatation, endoscopic urethrotomy, anastomotic repairs (rarely in the penile urethra), substitution repairs (ventral, dorsal, double-faced), free grafts of skin (full thickness and split thickness skin), oral mucosa, lingual mucosa, bladder mucosa, retroauricular skin (Wolf's graft), and skin flap repairs (circumferential, longitudinal and variants) from penile and (less commonly) scrotal skin, as well as the use of adjunctive maneuvers such as the use of advancement flaps for additional blood supply or defect coverage (**Table 1**).

**Urethral dilatation:** several methods for urethral dilatation exist: dilatation with a balloon, filiform and followers, urethral sounds (metallic or nonmetallic), or self-catheter dilatation. Urethral dilatation is carried out by gradual progressive stretching of the urethral lumen to a maximal diameter of 24 Fr. However, if performed aggressively, it will lead to further urethral trauma and scarring. It should be regarded as a palliative procedure and rarely as a curative one. It is mainly indicated in very select cases of strictures of the external meatus and fossa navicularis. It should be avoided in patients with LS as it often worsens the inflammatory process. Repeat dilatation should be avoided as it does not treat the underlying dense spongiofibrosis associated with more complex strictures.

**Internal urethrotomy:** also called direct vision internal urethrotomy (DVIU), it was first described by Sachse [13]. It consists of a cold-knife incision of the scar tissue allowing its release and healing of the underlying tissue by secondary epithelialization around a urethral catheter and thereby increasing the diameter of the urethral lumen. Apparently, only superficial strictures benefit from this treatment option when the incision is carried out through all thickness of the scar. Its success depends mostly on stricture length and degree of spongiofibrosis [14, 15]. It is best indicated for short strictures (<1.5 cm in length). Heyns et al. have suggested that if the stricture has not recurred within the first 3 months after a single DVIU (or dilatation), the stricture-free rate is 50–60% for up to 4 years of follow-up evaluation [16]. Recurrence rates vary in the penile and bulbar urethra: 84 and 58%, respectively [17]. Like dilatation, repeat urethrotomy is known to be associated with worse outcomes [15–18]. The failure rates of these minimally invasive strategies are poor and well documented, ranging from 9% after 1–3 years of follow-up [18]. At ≥4 years, the chance of stricture-free status is nearly 0% [19]. Open urethral reconstruction should be considered in case of recurrence after these minimally invasive attempts, unless the patient prefers intermittent self-catheterization as a chronic treatment plan. Nonetheless, despite the limitation of these minimally invasive procedures, they may become more useful if new generations of currently experimental modalities for scar modulation prove successful [20].

**Laser urethrotomy:** it utilizes several types of lasers, including CO2, argon, potassium titanyl phosphate (KTP), neodymium-doped yttrium aluminum garnet (Nd:YAG), holmium, and excimer lasers. They use different technologies and different depths of tissue penetration.

A meta-analysis of outcomes and complications of laser versus cold-knife urethrotomy compared unfavorably regarding laser: 12 versus 6.5%, respectively [21]. Laser urethrotomy may look appealing for the anterior urethra but with no definitive benefit over cold-knife urethrotomy.

**Grafts:** excision and primary reanastomosis, onlay grafting, and the use of flaps have been used for anterior urethral reconstruction. However, anastomotic urethroplasty rarely has a place in the penile shaft urethra due to the high risk of penile chordee or curvature, which impacts on erectile function and cosmesis. In the penile urethra, graft urethroplasty is traditionally used as it does not cause urethral tension. Several types of tissue can be used as onlay/inlay grafts: skin (full-thickness or split-thickness grafts), bladder mucosa, oral mucosa (buccal, labial, or lingual), and rectal mucosa. Historically, preputial skin grafts were the mainstay of grafting material until oral mucosa became popularized in the early 1990s [22, 23]. The crucial factor for grafting success is that the local tissue must have a healthy blood supply for normal graft taking. Single-stage graft urethroplasty uses the rich blood supply of spongiosal tissue ventrally or dorsally to support the graft, with overall success rates approaching 75–90% in the penile urethra, depending on stricture length [24, 25]. Little is found in the literature regarding both bladder epithelial grafts and rectal mucosal grafts, mainly due to lack of data about the process of take of these grafts.

Oral mucosal graft is currently the graft of choice, owing to their short harvest time, easy harvest technique, and the physical characteristics including resistance, durability, immunogenic properties, excellent vascularity, hairlessness, low oral morbidity, concealed donor site and high success rates [24, 25]. For these reasons, over the past 20 years, oral mucosal grafts have shown better handling characteristics and long-term stricture-free outcomes, and have replaced both penile skin grafts and flaps. However, patients with long and complex urethral abnormalities or with contraindications to oral mucosal graft use, such as those with leukoplakia, systemic skin disease of the oral cavity or history of chronic tobacco chewing may still necessitate split or full thickness skin grafts.

One controversy in anterior urethral grafting is related to dorsal or ventral placement of the graft on the urethra. Some urethral surgeons favor dorsal placement in both bulbar and urethral strictures, whereas others opt for ventral placement [26–31]. Although several studies have demonstrated comparable success rates for dorsal and ventral onlay grafting, the author of this chapter favors the use of dorsal placement of the graft in the penile urethra because the spongiosal vascularity in the ventral urethra is thinner and the graft support is less reliable when compared to the dorsal urethral surface.

**Flaps:** detailed knowledge of the blood supply to the penile skin and corpus spongiosum is mandatory for successful tissue harvest and transfer (see Section 2). Rather

**83**

circumference urethral reconstruction is mandatory.

*Historical Perspective and Innovations in Penile Urethroplasty*

than rely on the recipient site for survival, flaps depend on their native blood supply containing pedicle for transfer. Flaps can be classified by their blood supply, harvest technique or their method of transfer. Several types of flaps have been used in urethral reconstruction: penile skin, hairless scrotal skin, gracilis muscle, and the forearm or upper arm as free flaps or (microvascular free-transfer flaps). Popularized in the past, scrotal skin flaps are random rotational flaps that can be used for urethral and genital reconstruction [32–36]. However, their use for urethral reconstruction was associated with unacceptable long-term complications. They were predominantly used for repair of complex bulbar urethral strictures as these flaps were difficult to reach the penile

Various penile skin flaps have been described, which can be raised ventrally or dorsally on the penile shaft and taken longitudinally or circumferentially [37–39]. These flaps are fasciocutaneous in nature and are based on dartos fascia pedicle. The ventral, longitudinal flap, as described by Orandi, is best suited for penile shaft urethral strictures that do not reach the base of the penis or any part proximal to the penoscrotal angle because hair-bearing skin will inevitably be involved in the reconstruction. On the contrary, the transverse, circumferential preputial/distal penile skin flaps are long enough to bridge defects of the entire penile urethra and most of the bulbar urethra for example in panurethral defects. Ideally, flaps should be hairless, adapted to a moist environment, with a reliable vascular pedicle, mobile, and cosmetic. In general, anterior urethral reconstruction with the use of flaps has become less prevalent due to the increased popularity of oral mucosa grafts. A rise in prevalence of genital and urethral LS has also contributed to the near abdication of the use of flaps. Nonetheless, island skin flaps still find an important indication in reoperative cases with extensive spongiofibrosis and ischemic urethral mucosal plates where chances of graft take are minimal. These circumstances occur after irradiation, severe trauma, or infection. **One-stage vs. two (multiple)-stage reconstruction:** in the past, most penile urethral strictures were repaired through a staged approach [40–43]. However, because of advancements with pediatric hypospadias surgery, adult noncomplicated penile urethral strictures are now more commonly repaired with single-stage procedures. In 1995, Bracka described a two-stage urethral reconstruction, which enables a versatile approach to surgical reconstruction of previously failed, complex penile urethral strictures, especially hypospadias cripples [42]. The Johanson marsupialization was developed and subsequently reserved for penile urethral strictures [43]. Repairs in adults who failed hypospadias repair in childhood pose a particular reconstructive challenge because of dense scarring, tissue inelasticity, inflammation, impaired blood supply, and penile and urethral shortening from previous, often multiple, operations [44–47]. Penile urethroplasty should be performed in a single stage, whenever feasible, to avoid discomfort and disability to the patient from a multistage repair. Most strictures associated with trauma, infection, or instrumentation, where the penile skin, dartos fascia and spongiosum are not significantly damaged, can be approached through a single-stage procedure. On the other hand, presence of local infection or inflammation associated with a specific underlying disease process obliterated urethral segments with dense surrounding fibrosis, and a history of prior interventions, especially prior flap or hypospadias repairs, are contraindications for single-stage repairs and, therefore, should not be advised. The two-stage reconstruction involves surgical opening of the stricture, augmentation, or substitution (more commonly with use of oral mucosa grafting) of the diseased urethral segment and creation of temporary urethrostomy for drainage (first stage), followed between 4 and 6 months later by neourethral tubularization (second stage). Therefore, it should be confined to situations where it is inappropriate to maintain the axial integrity of the urethral plate and a full

urethra because of their short pedicle. They are practically abandoned.

*DOI: http://dx.doi.org/10.5772/intechopen.85908*

#### *Historical Perspective and Innovations in Penile Urethroplasty DOI: http://dx.doi.org/10.5772/intechopen.85908*

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

ferent depths of tissue penetration.

benefit over cold-knife urethrotomy.

still necessitate split or full thickness skin grafts.

rate is 50–60% for up to 4 years of follow-up evaluation [16]. Recurrence rates vary in the penile and bulbar urethra: 84 and 58%, respectively [17]. Like dilatation, repeat urethrotomy is known to be associated with worse outcomes [15–18]. The failure rates of these minimally invasive strategies are poor and well documented, ranging from 9% after 1–3 years of follow-up [18]. At ≥4 years, the chance of stricture-free status is nearly 0% [19]. Open urethral reconstruction should be considered in case of recurrence after these minimally invasive attempts, unless the patient prefers intermittent self-catheterization as a chronic treatment plan. Nonetheless, despite the limitation of these minimally invasive procedures, they may become more useful if new generations

of currently experimental modalities for scar modulation prove successful [20]. **Laser urethrotomy:** it utilizes several types of lasers, including CO2, argon, potassium titanyl phosphate (KTP), neodymium-doped yttrium aluminum garnet (Nd:YAG), holmium, and excimer lasers. They use different technologies and dif-

A meta-analysis of outcomes and complications of laser versus cold-knife urethrotomy compared unfavorably regarding laser: 12 versus 6.5%, respectively [21]. Laser urethrotomy may look appealing for the anterior urethra but with no definitive

**Grafts:** excision and primary reanastomosis, onlay grafting, and the use of flaps

One controversy in anterior urethral grafting is related to dorsal or ventral placement of the graft on the urethra. Some urethral surgeons favor dorsal placement in both bulbar and urethral strictures, whereas others opt for ventral placement [26–31]. Although several studies have demonstrated comparable success rates for dorsal and ventral onlay grafting, the author of this chapter favors the use of dorsal placement of the graft in the penile urethra because the spongiosal vascularity in the ventral urethra is thinner and the graft support is less reliable when compared to

**Flaps:** detailed knowledge of the blood supply to the penile skin and corpus spongiosum is mandatory for successful tissue harvest and transfer (see Section 2). Rather

have been used for anterior urethral reconstruction. However, anastomotic urethroplasty rarely has a place in the penile shaft urethra due to the high risk of penile chordee or curvature, which impacts on erectile function and cosmesis. In the penile urethra, graft urethroplasty is traditionally used as it does not cause urethral tension. Several types of tissue can be used as onlay/inlay grafts: skin (full-thickness or split-thickness grafts), bladder mucosa, oral mucosa (buccal, labial, or lingual), and rectal mucosa. Historically, preputial skin grafts were the mainstay of grafting material until oral mucosa became popularized in the early 1990s [22, 23]. The crucial factor for grafting success is that the local tissue must have a healthy blood supply for normal graft taking. Single-stage graft urethroplasty uses the rich blood supply of spongiosal tissue ventrally or dorsally to support the graft, with overall success rates approaching 75–90% in the penile urethra, depending on stricture length [24, 25]. Little is found in the literature regarding both bladder epithelial grafts and rectal mucosal grafts, mainly due to lack of data about the process of take of these grafts. Oral mucosal graft is currently the graft of choice, owing to their short harvest time, easy harvest technique, and the physical characteristics including resistance, durability, immunogenic properties, excellent vascularity, hairlessness, low oral morbidity, concealed donor site and high success rates [24, 25]. For these reasons, over the past 20 years, oral mucosal grafts have shown better handling characteristics and long-term stricture-free outcomes, and have replaced both penile skin grafts and flaps. However, patients with long and complex urethral abnormalities or with contraindications to oral mucosal graft use, such as those with leukoplakia, systemic skin disease of the oral cavity or history of chronic tobacco chewing may

**82**

the dorsal urethral surface.

than rely on the recipient site for survival, flaps depend on their native blood supply containing pedicle for transfer. Flaps can be classified by their blood supply, harvest technique or their method of transfer. Several types of flaps have been used in urethral reconstruction: penile skin, hairless scrotal skin, gracilis muscle, and the forearm or upper arm as free flaps or (microvascular free-transfer flaps). Popularized in the past, scrotal skin flaps are random rotational flaps that can be used for urethral and genital reconstruction [32–36]. However, their use for urethral reconstruction was associated with unacceptable long-term complications. They were predominantly used for repair of complex bulbar urethral strictures as these flaps were difficult to reach the penile urethra because of their short pedicle. They are practically abandoned.

Various penile skin flaps have been described, which can be raised ventrally or dorsally on the penile shaft and taken longitudinally or circumferentially [37–39]. These flaps are fasciocutaneous in nature and are based on dartos fascia pedicle. The ventral, longitudinal flap, as described by Orandi, is best suited for penile shaft urethral strictures that do not reach the base of the penis or any part proximal to the penoscrotal angle because hair-bearing skin will inevitably be involved in the reconstruction. On the contrary, the transverse, circumferential preputial/distal penile skin flaps are long enough to bridge defects of the entire penile urethra and most of the bulbar urethra for example in panurethral defects. Ideally, flaps should be hairless, adapted to a moist environment, with a reliable vascular pedicle, mobile, and cosmetic. In general, anterior urethral reconstruction with the use of flaps has become less prevalent due to the increased popularity of oral mucosa grafts. A rise in prevalence of genital and urethral LS has also contributed to the near abdication of the use of flaps. Nonetheless, island skin flaps still find an important indication in reoperative cases with extensive spongiofibrosis and ischemic urethral mucosal plates where chances of graft take are minimal. These circumstances occur after irradiation, severe trauma, or infection.

**One-stage vs. two (multiple)-stage reconstruction:** in the past, most penile urethral strictures were repaired through a staged approach [40–43]. However, because of advancements with pediatric hypospadias surgery, adult noncomplicated penile urethral strictures are now more commonly repaired with single-stage procedures. In 1995, Bracka described a two-stage urethral reconstruction, which enables a versatile approach to surgical reconstruction of previously failed, complex penile urethral strictures, especially hypospadias cripples [42]. The Johanson marsupialization was developed and subsequently reserved for penile urethral strictures [43].

Repairs in adults who failed hypospadias repair in childhood pose a particular reconstructive challenge because of dense scarring, tissue inelasticity, inflammation, impaired blood supply, and penile and urethral shortening from previous, often multiple, operations [44–47]. Penile urethroplasty should be performed in a single stage, whenever feasible, to avoid discomfort and disability to the patient from a multistage repair. Most strictures associated with trauma, infection, or instrumentation, where the penile skin, dartos fascia and spongiosum are not significantly damaged, can be approached through a single-stage procedure. On the other hand, presence of local infection or inflammation associated with a specific underlying disease process obliterated urethral segments with dense surrounding fibrosis, and a history of prior interventions, especially prior flap or hypospadias repairs, are contraindications for single-stage repairs and, therefore, should not be advised. The two-stage reconstruction involves surgical opening of the stricture, augmentation, or substitution (more commonly with use of oral mucosa grafting) of the diseased urethral segment and creation of temporary urethrostomy for drainage (first stage), followed between 4 and 6 months later by neourethral tubularization (second stage). Therefore, it should be confined to situations where it is inappropriate to maintain the axial integrity of the urethral plate and a full circumference urethral reconstruction is mandatory.

#### **7. Urethral reconstruction by stricture location**

In order to facilitate description and discussion of the various surgical procedures used for adult penile urethral reconstruction, we will group them according to stricture location in the urethra: (1) external meatus and fossa navicularis and (2) penile shaft urethra. Furthermore, a separate section will be devoted to procedures used for previously failed repairs or reoperative procedures (**Table 2**).

#### **7.1 External meatus and fossa navicularis**

Strictures involving exclusively the external meatus may be treated with **dilatation** if the stricture is not obliterative or the scarred tissue is minimal, the urethral lumen is still patent and elastic. It is considered palliative and should be attempted only once. Strictures associated with LS rarely respond to conservative options, such as dilatation, urethrotomy, and meatotomy.

**Meatotomy/meatoplasty:** either ventral or dorsal, meatotomy can be used for select meatal strictures. A ventral or dorsal midline incision is performed sharply, and the resultant mucosal edges are everted and reapproximated to the glans using 4–0 or 5–0 absorbable sutures. The dorsal side should be avoided, which can bleed profusely by cutting into the highly vascularized spongiosal tissue of the glans. The ventral approach usually leaves the patient with a slight degree of hypospadias that is usually well tolerated. The goal is to create a patent 22–24 F urethral lumen, particularly in cases of LS. Adjuvant topical therapy may be helpful. Meatal strictures that need meatoplasty usually require concomitant reconstruction of the fossa navicularis.

In 2004, Malone described a technique to relieve stenosis of the external urinary meatus resulting from LS [48]. The procedure is rapid and easy to perform on an outpatient basis, providing good cosmesis and functional voiding without spraying. The meatotomy is carried out dorsally avoiding a hypospadiac meatus. If the stricture extends into the fossa navicularis, oral mucosa graft reconstruction is performed. The final result is a slit-shaped with good caliber meatus at the tip of the glans. The procedure has been successfully reproduced by others [49].

**Longitudinal skin flap techniques:** initially reported in the early 1960s, it is based on the Y-V principle and used for short strictures of the meatus and fossa navicularis [50, 51]. Good outcomes can be achieved with these techniques, especially in patients with strictures resulting from instrumentation such as a large bore catheter or transurethral resection and those that are not associated with LS. The use of genital skin in LS patients has a high failure rate.

Several variants have been reported. Cohney in 1963 described a penile flap procedure based on a circumferential elevated random penile skin flap. The distal urethra is well open, but the patient is left with a less appealing cosmetic result and a retrusive meatus (**Figure 7A** and **B**). Blandy-Tresidder in 1967 developed a flap procedure based on dartos fascia vascularity. It also provides good functional outcomes, but only modest improvement of the cosmetic final appearance. The meatus is usually left at the coronal level (**Figure 7C** and **D**). The Brannen flap repair [52], a modification of Blandy's procedure, was described in 1976 to try to create a better cosmetic appearance of the glans and distal penile segment [53]. However, some mechanical problems associated with the flap advancement make this procedure inefficient and, therefore, offer marginal improvement in terms of cosmesis (**Figure 7E** and **F**). Designed to create a cosmetically normal meatus and glans penis, De Sy in 1984 further modified the Blandy and Brannen techniques using an advancement midline skin island flap [54]. However, the proximal portion of the flap is de-epithelialized leaving a distal skin island on dartos fascia (**Figure 7G** and **H**). Again, the mechanics of the flap advancement is inefficient.

**85**

**Table 2.**

*Historical Perspective and Innovations in Penile Urethroplasty*

• Transverse ventral/circumferential fasciocutaneous skin island flaps

○ Tubularized full-thickness skin graft (Devine, 1979)

*DOI: http://dx.doi.org/10.5772/intechopen.85908*

**A**. Ext. meatus and fossa navicularis • Meatotomy/meatoplasty

○ Blandy-Tresidder [51]

○ Cohney [50]

○ Brannen [52] ○ De Sy [53]

○ Jordan [54] ○ McAninch [39]

• Graft techniques

○ OMG [41]

○ Nandé (1998) ○ Nikolavsky et al. [64]

• Staged techniques ○ Bracka [41] ○ Jordan (2009)

○ Snodgrass [58] **B**. Penile shaft urethra • Flap reconstruction ○ Orandi flap [37] ○ Quartey flap [67] ○ Mcflinch flap (1993) ○ Turner-Warwick flap (1993)

• Graf reconstructions

• Staged reconstructions

○ Johanson's techniques [40] ○ Mesh graft urethroplasty [77] ○ Staged OMG urethroplasty • Tissue engineering/stem cell therapy

*Urethral reconstruction by stricture location.*

○ Inner prepuce [41]

• Combination of grafts and flaps [65] • Endourethroplasty techniques

• Tubularized incised plate urethroplasty

○ Dorsal OMG onlay (Barbagli, 1996)

○ Dorsal OMG inlay by ventral urethrotomy [59]

○ Penile inversion and one-sided dorsolateral OMG graft tech [75]

• Longitudinal skin flap techniques

#### **A**. Ext. meatus and fossa navicularis

	- Cohney [50]

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

In order to facilitate description and discussion of the various surgical procedures used for adult penile urethral reconstruction, we will group them according to stricture location in the urethra: (1) external meatus and fossa navicularis and (2) penile shaft urethra. Furthermore, a separate section will be devoted to procedures

Strictures involving exclusively the external meatus may be treated with **dilatation** if the stricture is not obliterative or the scarred tissue is minimal, the urethral lumen is still patent and elastic. It is considered palliative and should be attempted only once. Strictures associated with LS rarely respond to conservative options, such as dilata-

**Meatotomy/meatoplasty:** either ventral or dorsal, meatotomy can be used for select meatal strictures. A ventral or dorsal midline incision is performed sharply, and the resultant mucosal edges are everted and reapproximated to the glans using 4–0 or 5–0 absorbable sutures. The dorsal side should be avoided, which can bleed profusely by cutting into the highly vascularized spongiosal tissue of the glans. The ventral approach usually leaves the patient with a slight degree of hypospadias that is usually well tolerated. The goal is to create a patent 22–24 F urethral lumen, particularly in cases of LS. Adjuvant topical therapy may be helpful. Meatal strictures that need meatoplasty usually require concomitant reconstruction of the fossa navicularis.

In 2004, Malone described a technique to relieve stenosis of the external urinary meatus resulting from LS [48]. The procedure is rapid and easy to perform on an outpatient basis, providing good cosmesis and functional voiding without spraying. The meatotomy is carried out dorsally avoiding a hypospadiac meatus. If the stricture extends into the fossa navicularis, oral mucosa graft reconstruction is performed. The final result is a slit-shaped with good caliber meatus at the tip of the

**Longitudinal skin flap techniques:** initially reported in the early 1960s, it is based on the Y-V principle and used for short strictures of the meatus and fossa navicularis [50, 51]. Good outcomes can be achieved with these techniques, especially in patients with strictures resulting from instrumentation such as a large bore catheter or transurethral resection and those that are not associated with LS. The

Several variants have been reported. Cohney in 1963 described a penile flap procedure based on a circumferential elevated random penile skin flap. The distal urethra is well open, but the patient is left with a less appealing cosmetic result and a retrusive meatus (**Figure 7A** and **B**). Blandy-Tresidder in 1967 developed a flap procedure based on dartos fascia vascularity. It also provides good functional outcomes, but only modest improvement of the cosmetic final appearance. The meatus is usually left at the coronal level (**Figure 7C** and **D**). The Brannen flap repair [52], a modification of Blandy's procedure, was described in 1976 to try to create a better cosmetic appearance of the glans and distal penile segment [53]. However, some mechanical problems associated with the flap advancement make this procedure inefficient and, therefore, offer marginal improvement in terms of cosmesis (**Figure 7E** and **F**). Designed to create a cosmetically normal meatus and glans penis, De Sy in 1984 further modified the Blandy and Brannen techniques using an advancement midline skin island flap [54]. However, the proximal portion of the flap is de-epithelialized leaving a distal skin island on dartos fascia (**Figure 7G** and **H**). Again, the mechanics of the flap advancement is inefficient.

glans. The procedure has been successfully reproduced by others [49].

use of genital skin in LS patients has a high failure rate.

used for previously failed repairs or reoperative procedures (**Table 2**).

**7. Urethral reconstruction by stricture location**

**7.1 External meatus and fossa navicularis**

tion, urethrotomy, and meatotomy.

**84**

	- Jordan [54]
	- McAninch [39]
	- Tubularized full-thickness skin graft (Devine, 1979)
	- Inner prepuce [41]
	- OMG [41]
	- Nandé (1998)
	- Nikolavsky et al. [64]
	- Bracka [41]
	- Jordan (2009)
	- Snodgrass [58]
	- Flap reconstruction
		- Orandi flap [37]
		- Quartey flap [67]
		- Mcflinch flap (1993)
		- Turner-Warwick flap (1993)
	- Graf reconstructions
		- Dorsal OMG onlay (Barbagli, 1996)
		- Dorsal OMG inlay by ventral urethrotomy [59]
		- Penile inversion and one-sided dorsolateral OMG graft tech [75]
	- Staged reconstructions
		- Johanson's techniques [40]
		- Mesh graft urethroplasty [77]
		- Staged OMG urethroplasty
	- Tissue engineering/stem cell therapy

#### **Table 2.**

*Urethral reconstruction by stricture location.*

#### **Figure 7.**

*Schematic illustration of several techniques for surgical reconstruction of strictures of the urethral meatus and fossa navicularis. (A, B) Cohney's meatoplasty: an eccentric, transversely oriented, subcoronal flap is developed, and the urethrotomy is extended to normal urethra. The transverse flap is rotated into the urethrotomy defect. (C, D) Blandy's meatoplasty: creation of a midline flap. Urethrotomy is extended till normal urethral lumen. The flap is advanced into the urethrotomy defect. (E, F) Brannen's meatoplasty: a longer midline dartos-based flap is developed and is then widely advanced. (G, H) De Sy's meatoplasty: a midline flap similar to Brannen' technique is mobilized. The proximal portion of the flap is de-epithelialized leaving a distal skin island attached to a dartos pedicle. The de-epithelialized surface of the flap is anastomosed, and the ventral glans is reapproximated over the reconstruction (from Jordan and McCammon [96]).*

**Transverse ventral fasciocutaneous skin island flap:** as initially described by Jordan, this is a broad-based penile skin island flap oriented transversally on the ventral penile skin and elevated on a dartos fascia pedicle [55]. Minimal flap advancement is required, and the cosmetic appearance is virtually normal (**Figure 8**). McAninch modified this technique avoiding any disruption of the ventral glanular

**87**

*Historical Perspective and Innovations in Penile Urethroplasty*

integrity, which he assumed to provide a superior cosmetic result. This would be of paramount importance to the patient, overshadowing the functional success of the reconstruction. In his technique, the glans is exposed in either a glans-cap or a glans-

*Schematic illustration of Jordan's ventral transverse skin island flap procedure. (A–C) After urethrotomy is made till normal urethra, a ventral skin island flap is elevated above Buck's fascia, and the lateral glans wings are exposed. The skin island is rotated, transposed, and inverted into the urethrotomy defect. The glans wings are sutured ventrally. Inset shows details of the rotation, transposition, and inversion of the flap (from Jordan and McCammon [96]).*

**Graft techniques:** penile skin grafts were first employed and preferred tissue for urethroplasty before the advent of oral mucosa. Devine described a procedure using a tubularized full-thickness skin graft to reconstruct the external meatus and fossa navicularis [58]. Bracka reported in 2008 that the inner prepuce can be used for postischemic or infectious scarring as it is thin, flexible, with a reliable take, adapted to a moist environment and with no potential for hair growth (**Figure 10**) [43]. If not available, then postauricular skin graft is an acceptable alternative if oral mucosa cannot be harvested. However, due to its physical and biological characteristics, abundance, easy harvesting with minimal impact on the concealed donor site, and low oral morbidity, oral mucosa has become the most popular material for substitution or augmentation in urethral stricture repair. Oral mucosa can be used in strictures related to LS. It can be used in a single or staged procedure. Single-stage procedures are appropriate if the urethral plate is salvageable. In 1994, Snodgrass described a technique for the correction of pediatric hypospadias, which involved incision of the urethral plate followed by tubularization and secondary healing of the incised plate [59]. Although it produces good results in children, this procedure has not been associated with similar results in adults, often requiring inlay OMGs to increase the urethral lumen diameter [60]. Endourethroplasty techniques emerged in the early 1980s [61]. A few variants were reported later [62, 63]. However, due to inherent technical difficulties and complications of surgical reconstruction of distal penile and fossa navicularis strictures, these procedures have not become popular. Recently, Nikolavsky et al. has introduced a novel surgical technique for the reconstruction of distal urethral strictures using OMG through a transurethral approach with encouraging initial results (**Figures 11** and **12**) [64]. They designed this novel and elegant surgical concept in order to avoid the complications, technical difficulties, and limitations of the previous procedures used in this urethral area. The surgical procedure is applicable to the entire distal penile urethra, avoids an external ventral skin incision, preserves the glans penis, and employs oral mucosa for grafting, thus

*DOI: http://dx.doi.org/10.5772/intechopen.85908*

wings fashion (**Figure 9**) [56, 57].

**Figure 8.**

*Historical Perspective and Innovations in Penile Urethroplasty DOI: http://dx.doi.org/10.5772/intechopen.85908*

**Figure 8.**

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

**Transverse ventral fasciocutaneous skin island flap:** as initially described by Jordan, this is a broad-based penile skin island flap oriented transversally on the ventral penile skin and elevated on a dartos fascia pedicle [55]. Minimal flap advancement is required, and the cosmetic appearance is virtually normal (**Figure 8**). McAninch modified this technique avoiding any disruption of the ventral glanular

*reapproximated over the reconstruction (from Jordan and McCammon [96]).*

*Schematic illustration of several techniques for surgical reconstruction of strictures of the urethral meatus and fossa navicularis. (A, B) Cohney's meatoplasty: an eccentric, transversely oriented, subcoronal flap is developed, and the urethrotomy is extended to normal urethra. The transverse flap is rotated into the urethrotomy defect. (C, D) Blandy's meatoplasty: creation of a midline flap. Urethrotomy is extended till normal urethral lumen. The flap is advanced into the urethrotomy defect. (E, F) Brannen's meatoplasty: a longer midline dartos-based flap is developed and is then widely advanced. (G, H) De Sy's meatoplasty: a midline flap similar to Brannen' technique is mobilized. The proximal portion of the flap is de-epithelialized leaving a distal skin island attached to a dartos pedicle. The de-epithelialized surface of the flap is anastomosed, and the ventral glans is* 

**86**

**Figure 7.**

*Schematic illustration of Jordan's ventral transverse skin island flap procedure. (A–C) After urethrotomy is made till normal urethra, a ventral skin island flap is elevated above Buck's fascia, and the lateral glans wings are exposed. The skin island is rotated, transposed, and inverted into the urethrotomy defect. The glans wings are sutured ventrally. Inset shows details of the rotation, transposition, and inversion of the flap (from Jordan and McCammon [96]).*

integrity, which he assumed to provide a superior cosmetic result. This would be of paramount importance to the patient, overshadowing the functional success of the reconstruction. In his technique, the glans is exposed in either a glans-cap or a glanswings fashion (**Figure 9**) [56, 57].

**Graft techniques:** penile skin grafts were first employed and preferred tissue for urethroplasty before the advent of oral mucosa. Devine described a procedure using a tubularized full-thickness skin graft to reconstruct the external meatus and fossa navicularis [58]. Bracka reported in 2008 that the inner prepuce can be used for postischemic or infectious scarring as it is thin, flexible, with a reliable take, adapted to a moist environment and with no potential for hair growth (**Figure 10**) [43]. If not available, then postauricular skin graft is an acceptable alternative if oral mucosa cannot be harvested. However, due to its physical and biological characteristics, abundance, easy harvesting with minimal impact on the concealed donor site, and low oral morbidity, oral mucosa has become the most popular material for substitution or augmentation in urethral stricture repair. Oral mucosa can be used in strictures related to LS. It can be used in a single or staged procedure. Single-stage procedures are appropriate if the urethral plate is salvageable. In 1994, Snodgrass described a technique for the correction of pediatric hypospadias, which involved incision of the urethral plate followed by tubularization and secondary healing of the incised plate [59]. Although it produces good results in children, this procedure has not been associated with similar results in adults, often requiring inlay OMGs to increase the urethral lumen diameter [60]. Endourethroplasty techniques emerged in the early 1980s [61]. A few variants were reported later [62, 63]. However, due to inherent technical difficulties and complications of surgical reconstruction of distal penile and fossa navicularis strictures, these procedures have not become popular. Recently, Nikolavsky et al. has introduced a novel surgical technique for the reconstruction of distal urethral strictures using OMG through a transurethral approach with encouraging initial results (**Figures 11** and **12**) [64]. They designed this novel and elegant surgical concept in order to avoid the complications, technical difficulties, and limitations of the previous procedures used in this urethral area. The surgical procedure is applicable to the entire distal penile urethra, avoids an external ventral skin incision, preserves the glans penis, and employs oral mucosa for grafting, thus

#### **Figure 9.**

*Fasciocutaneous distal penile flap urethroplasty as described by McAninch. (A–H) Urethral exposure followed by ventral longitudinal urethrotomy. The fossa navicularis is exposed with either a glans-cap or a glans-wings technique. A fasciocutaneous distal, transverse, ventral penile flap is developed. The urethral stricture can be corrected by either a ventral onlay or a neourethral tube. The glans wings or cap is sutured to cover the flap reconstruction (from Armenakas and McAninch [97]).*

achieving both excellent functional and cosmetic results. This procedure is especially indicated for patients affected by LS-related distal strictures, where only oral mucosal grafts are advised.

**Combined flap and graft technique:** in 2011, Gelman and Sohn described a procedure combining a dorsal onlay graft with a ventral onlay flap for a subset of patient with ischemic, obliterated distal strictures who had already failed urethral repair, or who had a history of hypospadias [65]. This procedure is particularly useful in strictures associated with compromised urethral plates due to ischemia and dense scarring from previous repairs and when a two-stage procedure is not desired (**Figure 13**).

**Staged techniques:** these techniques are best suited for patients who have failed hypospadias repairs or the urethral plate is deficient or densely scarred, or if there is involvement of LS. These techniques may be considered more versatile than flap repairs and are preferred in patients with LS. The modern staged urethral reconstruction described by Bracka in 1995 is a versatile approach to difficult anterior urethral reconstructions [41–43]. In Bracka's procedure, the diseased urethra is excised entirely and the urethral plate is replaced by an OM onlay graft (**Figure 10**). Jordan later described a similar technique [66].

**89**

**Figure 11.**

**Figure 10.**

*Historical Perspective and Innovations in Penile Urethroplasty*

*Two-stage distal urethra reconstruction as described by Bracka. (a–b) Marsupialization of the urethra and placement of the oral mucosal graft after excision of the diseased urethral mucosa at the first stage. Aspect of* 

(b) (c)

*the graft 6 months later, which is then prepared for tubularization at the second stage.*

(d) (e)

*Transurethral ventral buccal mucosa graft inlay urethroplasty for reconstruction of fossa navicularis and distal urethral meatus as described by Nikolavsky. (a-e) Transurethral ventral shallow resection of scar tissue. Placement of double-armed suture through buccal graft and through apex of urethrotomy (inside out). External apical suture tying, meatal BMG edge fixation, and additional inside-out quilting of the graft with doublearmed sutures (reproduced with permission from Springer Science + Business Media Dordrecht, Ref. [62]).*

(a)

*DOI: http://dx.doi.org/10.5772/intechopen.85908*

#### **Figure 10.**

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

achieving both excellent functional and cosmetic results. This procedure is especially indicated for patients affected by LS-related distal strictures, where only oral

*Fasciocutaneous distal penile flap urethroplasty as described by McAninch. (A–H) Urethral exposure followed by ventral longitudinal urethrotomy. The fossa navicularis is exposed with either a glans-cap or a glans-wings technique. A fasciocutaneous distal, transverse, ventral penile flap is developed. The urethral stricture can be corrected by either a ventral onlay or a neourethral tube. The glans wings or cap is sutured to cover the flap* 

**Combined flap and graft technique:** in 2011, Gelman and Sohn described a procedure combining a dorsal onlay graft with a ventral onlay flap for a subset of patient with ischemic, obliterated distal strictures who had already failed urethral repair, or who had a history of hypospadias [65]. This procedure is particularly useful in strictures associated with compromised urethral plates due to ischemia and dense scarring from previous repairs and when a two-stage procedure is not desired (**Figure 13**).

**Staged techniques:** these techniques are best suited for patients who have failed hypospadias repairs or the urethral plate is deficient or densely scarred, or if there is involvement of LS. These techniques may be considered more versatile than flap repairs and are preferred in patients with LS. The modern staged urethral reconstruction described by Bracka in 1995 is a versatile approach to difficult anterior urethral reconstructions [41–43]. In Bracka's procedure, the diseased urethra is excised entirely and the urethral plate is replaced by an OM onlay graft (**Figure 10**).

**88**

mucosal grafts are advised.

*reconstruction (from Armenakas and McAninch [97]).*

**Figure 9.**

Jordan later described a similar technique [66].

*Two-stage distal urethra reconstruction as described by Bracka. (a–b) Marsupialization of the urethra and placement of the oral mucosal graft after excision of the diseased urethral mucosa at the first stage. Aspect of the graft 6 months later, which is then prepared for tubularization at the second stage.*

#### **Figure 11.**

*Transurethral ventral buccal mucosa graft inlay urethroplasty for reconstruction of fossa navicularis and distal urethral meatus as described by Nikolavsky. (a-e) Transurethral ventral shallow resection of scar tissue. Placement of double-armed suture through buccal graft and through apex of urethrotomy (inside out). External apical suture tying, meatal BMG edge fixation, and additional inside-out quilting of the graft with doublearmed sutures (reproduced with permission from Springer Science + Business Media Dordrecht, Ref. [62]).*

#### **Figure 12.**

*Intraoperative demonstration of the procedure described in Figure 11 (reproduced with permission from Springer Science + Business Media Dordrecht, Ref. [62]).*

#### **Figure 13.**

*Schematic illustration of single-stage, combined flap graft technique as described by Gelman. (A–C) Oral mucosal graft is placed and quilted dorsally followed by closure of the urethrotomy defect by a penile skin flap (from Gelman and Sohn, Ref. [63]).*

#### **7.2 Penile shaft urethra**

For penile shaft urethral strictures, a stricturotomy and onlay or inlay patch graft, or alternatively a flap reconstruction, can be used for simple strictures. More complex cases may eventually require total excision of the strictured area and circumferential reconstruction with OM grafts or penile skin flap. In more complex situations, such as after previous failed repairs and compromised or obliterated urethras, a staged reconstruction is preferable. Penile urethral strictures are rarely cured by dilatation or DVIU. If either of these procedures fail once, the chance of a better outcome with a second attempt is almost nil, making urethroplasty the only

**91**

**Figure 14.**

*Historical Perspective and Innovations in Penile Urethroplasty*

even in short strictures, as ventral curvature usually occurs.

curative option. Anastomotic urethroplasty should be avoided in the penile urethra,

Patient advanced age and comorbidities may steer the urologist away from open surgery. In these circumstances, periodic urethral (self)-dilatation or definitive

**Flap reconstructions:** penile skin island flaps may be elevated in a longitudinal

*Orandi flap:* the Orandi flap is a longitudinal, ventral, fasciocutaneous island

With the penis on stretch, a longitudinal nonhair-bearing skin island is marked on the ventral aspect of the penis. The description of the surgical technique is outlined in **Figure 14**. The penis is snugly dressed to avoid hematoma. Drains are rarely required. Patients are kept on strict bed rest for 3–5 days to minimize swelling. Intravenous antibiotics are administered for at least 48 h, followed by oral antibiotic prophylaxis for one additional week. Erections should be avoided. The use of a suprapubic catheter for urinary drainage is not mandatory but preferable, which should be kept for 2 weeks. The urethral catheter is left plugged to act as a stent only. After 2–3 weeks, the urethral catheter is removed and the patient is sent home with the suprapubic tube occluded, allowing the patient to resume urethral voiding. The suprapubic tube is removed after a few days of normal urethral voiding. If a

*Orandi flap procedure. (A–C) Deep skin incision is made over the strictured urethra. Dotted line indicates skin incision. Dartos pedicled flap is created lateral to the superficial skin incision, which will cover the urethrotomy* 

*defect. The skin is closed in the midline (from Elliott and McAninch [98]).*

penile flap that is appropriate for single-stage reconstruction of strictures of the penile shaft urethra [37]. Inclusion of the distal bulbar urethra in the reconstruction may be hampered by hair-bearing skin of the more proximal part of the flap. Careful planning of the flap is critical before skin incision to avoid jeopardizing the flap design and its blood supply. The flap must be handled meticulously with the use of atraumatic surgical tools and eventually loupe magnification. It then must be mobilized gently to preserve its arterial and venous blood supply. The type and size of suture material is paramount to minimize

*DOI: http://dx.doi.org/10.5772/intechopen.85908*

urethrostomy should be strongly considered.

tissue reaction.

or transverse, circumferential fashion, and variants.

#### *Historical Perspective and Innovations in Penile Urethroplasty DOI: http://dx.doi.org/10.5772/intechopen.85908*

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

**90**

**7.2 Penile shaft urethra**

*(from Gelman and Sohn, Ref. [63]).*

**Figure 12.**

**Figure 13.**

*Springer Science + Business Media Dordrecht, Ref. [62]).*

For penile shaft urethral strictures, a stricturotomy and onlay or inlay patch graft, or alternatively a flap reconstruction, can be used for simple strictures. More complex cases may eventually require total excision of the strictured area and circumferential reconstruction with OM grafts or penile skin flap. In more complex situations, such as after previous failed repairs and compromised or obliterated urethras, a staged reconstruction is preferable. Penile urethral strictures are rarely cured by dilatation or DVIU. If either of these procedures fail once, the chance of a better outcome with a second attempt is almost nil, making urethroplasty the only

*Schematic illustration of single-stage, combined flap graft technique as described by Gelman. (A–C) Oral mucosal graft is placed and quilted dorsally followed by closure of the urethrotomy defect by a penile skin flap* 

*Intraoperative demonstration of the procedure described in Figure 11 (reproduced with permission from* 

curative option. Anastomotic urethroplasty should be avoided in the penile urethra, even in short strictures, as ventral curvature usually occurs.

Patient advanced age and comorbidities may steer the urologist away from open surgery. In these circumstances, periodic urethral (self)-dilatation or definitive urethrostomy should be strongly considered.

**Flap reconstructions:** penile skin island flaps may be elevated in a longitudinal or transverse, circumferential fashion, and variants.

*Orandi flap:* the Orandi flap is a longitudinal, ventral, fasciocutaneous island penile flap that is appropriate for single-stage reconstruction of strictures of the penile shaft urethra [37]. Inclusion of the distal bulbar urethra in the reconstruction may be hampered by hair-bearing skin of the more proximal part of the flap. Careful planning of the flap is critical before skin incision to avoid jeopardizing the flap design and its blood supply. The flap must be handled meticulously with the use of atraumatic surgical tools and eventually loupe magnification. It then must be mobilized gently to preserve its arterial and venous blood supply. The type and size of suture material is paramount to minimize tissue reaction.

With the penis on stretch, a longitudinal nonhair-bearing skin island is marked on the ventral aspect of the penis. The description of the surgical technique is outlined in **Figure 14**. The penis is snugly dressed to avoid hematoma. Drains are rarely required. Patients are kept on strict bed rest for 3–5 days to minimize swelling. Intravenous antibiotics are administered for at least 48 h, followed by oral antibiotic prophylaxis for one additional week. Erections should be avoided. The use of a suprapubic catheter for urinary drainage is not mandatory but preferable, which should be kept for 2 weeks. The urethral catheter is left plugged to act as a stent only. After 2–3 weeks, the urethral catheter is removed and the patient is sent home with the suprapubic tube occluded, allowing the patient to resume urethral voiding. The suprapubic tube is removed after a few days of normal urethral voiding. If a

#### **Figure 14.**

*Orandi flap procedure. (A–C) Deep skin incision is made over the strictured urethra. Dotted line indicates skin incision. Dartos pedicled flap is created lateral to the superficial skin incision, which will cover the urethrotomy defect. The skin is closed in the midline (from Elliott and McAninch [98]).*

fistula develops, the urethral catheter is not reinserted and the suprapubic diversion is maintained for another week. If still persistent, then it should be repaired after 4–6 months.

The Orandi flap is a reliable and relatively easy flap to harvest. It is a useful solution for a single-stage reconstruction of penile urethral strictures.

*Quartey flap*: in 1983, Quartey described a one-stage flap urethroplasty technique using a transverse distal penile or preputial island of skin as a flap, which is supplied axially by the superficial external pudendal vessels for penile urethral strictures with possible extended application to the entire penile and bulbar urethra and even difficult posterior urethral strictures [67, 68]. He described the possibility of this island of skin being used either as a patch or as a tube. In very long strictures, the complete circumference of the distal penile skin can be extended ventrally and proximally toward the base of the penis in the hairless area. This flap design granted it the term "hockey stick island flap" (**Figure 15**).

*McAninch flap:* in 1993, McAninch reported the initial circular fasciocutaneous penile skin flap for the reconstruction of extensive anterior urethral strictures [39]. This flap is a variant of the flap described by Quartey 10 years earlier with the difference that this fasciocutaneous flap uses Buck's fascia as a paddle to carry the vascular pedicle to the distal flap skin. It can provide a hairless flap up to 15 cm in length, making this flap, like Quartey's flap, extremely versatile. It can be used in uncircumcised as well as circumcised men. The width of the flap varies from 2.0 to 2.5 cm, depending on the stricture characteristics. With the penis on traction, the distal incision is

#### **Figure 15.**

*Quartey flap procedure. (A, B) Hockey stick skin island flap is fashioned. The length of the flap may be tailored as needed. After ventral longitudinal urethrotomy, the flap is anastomosed similar to the Orandi technique.*

**93**

**Figure 16.**

*McAninch [99]).*

*Historical Perspective and Innovations in Penile Urethroplasty*

and functional results are excellent in experienced hands.

carried down deeply beneath the pedicle just beneath Buck's fascia, but superficial to the dorsal neurovascular bundle (dorsally), circumflex vessels (laterally), and urethra (ventrally). The proximal incision extends proximally to the base of the penis through a dissection plane beneath the skin and subdermal or dartos fascia (**Figure 16**). The flap and pedicle can be divided either ventrally or dorsally and rotated to cover the urethral area as an onlay flap. This flap also allows reconstruction of complex strictures of various lengths in a single stage even in circumcised patients. The cosmetic

*Turner-Warwick flap:* described by Turner-Warwick, this is a bilateral, longitudinal, ventral-based pedicle skin flap supported by right and left ventrolateral branches of the external pudendal artery. Although it may be employed in penile urethral stricture repair, this flap is most useful in bulbar urethral reconstruction [69].

**Graft reconstructions:** historically, grafts have been used for reconstruction of anterior urethral strictures since the early 1960s [70]. Several different types of graft material have been used with favorable results since then, but in the modern era, oral mucosa has become the graft of choice for its excellent graft characteristics

*Dorsal OMG onlay technique (Barbagli):* ventral onlay grafts are usually discouraged on the corpus spongiosum if the penile urethra is thin, not allowing spongioplasty maneuvers to support the graft and optimize graft take. Therefore, a dorsal onlay approach is used in this urethral segment. The urethra can be exposed either through a circular, subcoronal incision followed by penile shaft degloving, or a ventral midline incision, the latter one being favored by the author of this chapter for its associated lower local morbidity. After identifying the obstruction of a soft 20F Nelaton catheter or Bougie-a-Boule, the urethra is mobilized circumferentially off of the corpora cavernosa along the stricture length. The urethra is rotated 180° for preparation of the dorsal urethrotomy after placing marking stitches at both ends of the stricture. The graft is quilted to the corpora cavernosa, and the edges of the graft and urethrotomy are sewn together. Barbagli et al. have suggested the use of fibrin glue for one-stage penile graft urethroplasty. The authors reported that this new adjunct was safe and effective, with limited complications and satisfactory

*Dorsal OMG inlay through a ventral sagittal urethrotomy (Asopa):* in 2001, Asopa described the technique of dorsal OMG inlay through a ventral sagittal urethrotomy approach as an alternative to the Barbagli technique for the repair of penile strictures (**Figure 17**). The advantages are a simpler dissection, no mobilization of the urethra, and preservation of the urethral blood supply through circumflex and

*McAninch fasciocutaneous circular distal penile island flap. (A–D) Flap harvesting followed by ventral division of flap and pedicle, and then, it is rotated and anastomosed to the urethrotomy defect (from* 

*DOI: http://dx.doi.org/10.5772/intechopen.85908*

and ease and low morbidity of harvest.

preliminary outcomes [71].

#### *Historical Perspective and Innovations in Penile Urethroplasty DOI: http://dx.doi.org/10.5772/intechopen.85908*

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

tion for a single-stage reconstruction of penile urethral strictures.

it the term "hockey stick island flap" (**Figure 15**).

4–6 months.

fistula develops, the urethral catheter is not reinserted and the suprapubic diversion is maintained for another week. If still persistent, then it should be repaired after

The Orandi flap is a reliable and relatively easy flap to harvest. It is a useful solu-

*Quartey flap*: in 1983, Quartey described a one-stage flap urethroplasty technique using a transverse distal penile or preputial island of skin as a flap, which is supplied axially by the superficial external pudendal vessels for penile urethral strictures with possible extended application to the entire penile and bulbar urethra and even difficult posterior urethral strictures [67, 68]. He described the possibility of this island of skin being used either as a patch or as a tube. In very long strictures, the complete circumference of the distal penile skin can be extended ventrally and proximally toward the base of the penis in the hairless area. This flap design granted

*McAninch flap:* in 1993, McAninch reported the initial circular fasciocutaneous penile skin flap for the reconstruction of extensive anterior urethral strictures [39]. This flap is a variant of the flap described by Quartey 10 years earlier with the difference that this fasciocutaneous flap uses Buck's fascia as a paddle to carry the vascular pedicle to the distal flap skin. It can provide a hairless flap up to 15 cm in length, making this flap, like Quartey's flap, extremely versatile. It can be used in uncircumcised as well as circumcised men. The width of the flap varies from 2.0 to 2.5 cm, depending on the stricture characteristics. With the penis on traction, the distal incision is

**92**

**Figure 15.**

*technique.*

*Quartey flap procedure. (A, B) Hockey stick skin island flap is fashioned. The length of the flap may be tailored as needed. After ventral longitudinal urethrotomy, the flap is anastomosed similar to the Orandi*  carried down deeply beneath the pedicle just beneath Buck's fascia, but superficial to the dorsal neurovascular bundle (dorsally), circumflex vessels (laterally), and urethra (ventrally). The proximal incision extends proximally to the base of the penis through a dissection plane beneath the skin and subdermal or dartos fascia (**Figure 16**). The flap and pedicle can be divided either ventrally or dorsally and rotated to cover the urethral area as an onlay flap. This flap also allows reconstruction of complex strictures of various lengths in a single stage even in circumcised patients. The cosmetic and functional results are excellent in experienced hands.

*Turner-Warwick flap:* described by Turner-Warwick, this is a bilateral, longitudinal, ventral-based pedicle skin flap supported by right and left ventrolateral branches of the external pudendal artery. Although it may be employed in penile urethral stricture repair, this flap is most useful in bulbar urethral reconstruction [69].

**Graft reconstructions:** historically, grafts have been used for reconstruction of anterior urethral strictures since the early 1960s [70]. Several different types of graft material have been used with favorable results since then, but in the modern era, oral mucosa has become the graft of choice for its excellent graft characteristics and ease and low morbidity of harvest.

*Dorsal OMG onlay technique (Barbagli):* ventral onlay grafts are usually discouraged on the corpus spongiosum if the penile urethra is thin, not allowing spongioplasty maneuvers to support the graft and optimize graft take. Therefore, a dorsal onlay approach is used in this urethral segment. The urethra can be exposed either through a circular, subcoronal incision followed by penile shaft degloving, or a ventral midline incision, the latter one being favored by the author of this chapter for its associated lower local morbidity. After identifying the obstruction of a soft 20F Nelaton catheter or Bougie-a-Boule, the urethra is mobilized circumferentially off of the corpora cavernosa along the stricture length. The urethra is rotated 180° for preparation of the dorsal urethrotomy after placing marking stitches at both ends of the stricture. The graft is quilted to the corpora cavernosa, and the edges of the graft and urethrotomy are sewn together. Barbagli et al. have suggested the use of fibrin glue for one-stage penile graft urethroplasty. The authors reported that this new adjunct was safe and effective, with limited complications and satisfactory preliminary outcomes [71].

*Dorsal OMG inlay through a ventral sagittal urethrotomy (Asopa):* in 2001, Asopa described the technique of dorsal OMG inlay through a ventral sagittal urethrotomy approach as an alternative to the Barbagli technique for the repair of penile strictures (**Figure 17**). The advantages are a simpler dissection, no mobilization of the urethra, and preservation of the urethral blood supply through circumflex and

#### **Figure 16.**

*McAninch fasciocutaneous circular distal penile island flap. (A–D) Flap harvesting followed by ventral division of flap and pedicle, and then, it is rotated and anastomosed to the urethrotomy defect (from McAninch [99]).*

**Figure 17.** *(A-B) Asopa technique used in long penile urethral stricture approached through a ventral incision.*

perforating vessels [72]. However, it involves an extra urethrotomy, which may potentially lead to additional urethral trauma. In the bulbar urethra, it can be used in combination with a second ventrally placed graft. Again, either a degloving or a ventral midline incision can be used. An alternative perineal approach for exclusive penile urethral strictures has been recently adapted from the Kulkarni perineal approach to panurethral stricture repair (**Figure 18**) [73, 74]. This perineal approach avoids the morbidity and less optimal cosmetic results of a penile incision and scar, allowing the performance of penile graft urethroplasty through either Barbagli's dorsal onlay or Asopa's dorsal inlay or Kulkarni's one-sided dorsolateral approach with equivalent functional results.

*Penile inversion and one-sided dorsolateral OMG graft technique* (*Kulkarni*)*:* Kulkarni first described the technique of perineal approach with penile inversion to expose the full length of anterior urethra for reconstruction of panurethral strictures with avoidance of a penile incision. In 2009, he reported and popularized a slight but important modification of his original technique, which involved a one-sided urethral dissection [75]. The preservation of the one-sided vascular supply to the urethra and its entire muscular and neurogenic support should represent a slight but significant step toward perfecting the surgical technique of urethral reconstruction using a minimally invasive approach. The preservation of the vascular blood supply

#### **Figure 18.**

*Kulkarni's one-sided dorsal onlay graft for anterior urethroplasty for long urethral strictures. (a-c) The penile shaft has been inverted into the perineum where the entire reconstruction is performed. This technique can be used to repair the entire length of the anterior urethra (reproduced with permission from Sanjay Kulkarni, MD).*

**95**

**Figure 19.**

*Historical Perspective and Innovations in Penile Urethroplasty*

to one side of the urethra along with its muscular and neural support had a significant impact on functional outcomes. The whole operation is performed through the perineal approach only, making this a minimally invasive approach (**Figure 18**). **Staged reconstructions:** staged urethroplasty is used for complicated strictures with significant scar tissue involved, failed hypospadias repair, multiple prior urethroplasty failures, long obliterative strictures, presence of diverticulum or fistulation, and strictures caused by lichen sclerosus, where complete removal of the native diseased urethra may be necessary. In all these circumstances, there is absence of enough healthy tissue to allow a successful one-stage reconstruction. Staged reconstructions are based on the marsupialization of the strictured urethra and involve a planned repair strategy characterized by more than one operation and inherent free tissue transfer. Classically, the term "two-stage urethroplasty" is a misnomer as a significant number of these patients end up requiring more than two operations to produce the final result, that is, a patent tubularized urethra [76]. Alternatives to staged urethroplasty are definitive perineal urethrostomy, combined double face grafting, or other less common

*Johanson's technique:* in the first stage, the penis is placed on stretch and the distal end of the stricture is identified. A longitudinal penile skin incision is carried out over the strictured area. The stricturotomy is extended proximally until normal urethra is exposed. The lateral edges of the urethra are sewn with the skin edges (**Figure 19**). Because voiding in a standing position is not possible without dribbling, soiling of the scrotum, and a forward stream, patients may be offered a temporary perineal urethrostomy, if necessary, which is closed at the second stage of the reconstruction. At the second stage, the urethral plate is tubularized and a

*Mesh graft urethroplasty:* this procedure was first described by Schreiter and Noll [77]. In the first stage, a longitudinal incision is made over the strictured urethra. The urethra is marsupialized preserving the native urethral plate. The split thickness graft (or foreskin) is harvested in the standard fashion with an

*Johanson's two-stage procedure. (A–C) The anastomosis of the skin edges and the longitudinal urethrotomy is performed at the first stage. The urethrotomy is fashioned as a neourethral tube at the second stage.* 

*Modification with use of oral mucosal graft has been described.*

dartos flap is developed to cover the suture line to avoid fistulation.

*DOI: http://dx.doi.org/10.5772/intechopen.85908*

individualized procedures.

#### *Historical Perspective and Innovations in Penile Urethroplasty DOI: http://dx.doi.org/10.5772/intechopen.85908*

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

approach with equivalent functional results.

perforating vessels [72]. However, it involves an extra urethrotomy, which may potentially lead to additional urethral trauma. In the bulbar urethra, it can be used in combination with a second ventrally placed graft. Again, either a degloving or a ventral midline incision can be used. An alternative perineal approach for exclusive penile urethral strictures has been recently adapted from the Kulkarni perineal approach to panurethral stricture repair (**Figure 18**) [73, 74]. This perineal approach avoids the morbidity and less optimal cosmetic results of a penile incision and scar, allowing the performance of penile graft urethroplasty through either Barbagli's dorsal onlay or Asopa's dorsal inlay or Kulkarni's one-sided dorsolateral

*(A-B) Asopa technique used in long penile urethral stricture approached through a ventral incision.*

*Penile inversion and one-sided dorsolateral OMG graft technique* (*Kulkarni*)*:* Kulkarni first described the technique of perineal approach with penile inversion to expose the full length of anterior urethra for reconstruction of panurethral strictures with avoidance of a penile incision. In 2009, he reported and popularized a slight but important modification of his original technique, which involved a one-sided urethral dissection [75]. The preservation of the one-sided vascular supply to the urethra and its entire muscular and neurogenic support should represent a slight but significant step toward perfecting the surgical technique of urethral reconstruction using a minimally invasive approach. The preservation of the vascular blood supply

(a) (b) (c)

*Kulkarni's one-sided dorsal onlay graft for anterior urethroplasty for long urethral strictures. (a-c) The penile shaft has been inverted into the perineum where the entire reconstruction is performed. This technique can be used to repair the entire length of the anterior urethra (reproduced with permission from Sanjay Kulkarni, MD).*

**94**

**Figure 18.**

**Figure 17.**

to one side of the urethra along with its muscular and neural support had a significant impact on functional outcomes. The whole operation is performed through the perineal approach only, making this a minimally invasive approach (**Figure 18**).

**Staged reconstructions:** staged urethroplasty is used for complicated strictures with significant scar tissue involved, failed hypospadias repair, multiple prior urethroplasty failures, long obliterative strictures, presence of diverticulum or fistulation, and strictures caused by lichen sclerosus, where complete removal of the native diseased urethra may be necessary. In all these circumstances, there is absence of enough healthy tissue to allow a successful one-stage reconstruction. Staged reconstructions are based on the marsupialization of the strictured urethra and involve a planned repair strategy characterized by more than one operation and inherent free tissue transfer. Classically, the term "two-stage urethroplasty" is a misnomer as a significant number of these patients end up requiring more than two operations to produce the final result, that is, a patent tubularized urethra [76]. Alternatives to staged urethroplasty are definitive perineal urethrostomy, combined double face grafting, or other less common individualized procedures.

*Johanson's technique:* in the first stage, the penis is placed on stretch and the distal end of the stricture is identified. A longitudinal penile skin incision is carried out over the strictured area. The stricturotomy is extended proximally until normal urethra is exposed. The lateral edges of the urethra are sewn with the skin edges (**Figure 19**). Because voiding in a standing position is not possible without dribbling, soiling of the scrotum, and a forward stream, patients may be offered a temporary perineal urethrostomy, if necessary, which is closed at the second stage of the reconstruction. At the second stage, the urethral plate is tubularized and a dartos flap is developed to cover the suture line to avoid fistulation.

*Mesh graft urethroplasty:* this procedure was first described by Schreiter and Noll [77]. In the first stage, a longitudinal incision is made over the strictured urethra. The urethra is marsupialized preserving the native urethral plate. The split thickness graft (or foreskin) is harvested in the standard fashion with an

#### **Figure 19.**

*Johanson's two-stage procedure. (A–C) The anastomosis of the skin edges and the longitudinal urethrotomy is performed at the first stage. The urethrotomy is fashioned as a neourethral tube at the second stage. Modification with use of oral mucosal graft has been described.*

#### **Figure 20.**

*Mesh graft urethroplasty as described by Schreiter. Meshed skin graft has been placed on the wound ground and quilted to the host bed (first stage). The prepared urethral plate is tubularized approximately 6 months later (second stage).*

electrical dermatome and is meshed with a mechanical skin mesher using a 1:15 ratio sheet. The graft is placed on the wound ground lateral to the preserved urethral plate (**Figure 20**). The graft is fixed by running 5–0 monofilament sutures. The second stage (urethral tubularization) is performed in a standard fashion. In a study by Carr et al., success was achieved in 80% at a median follow-up of 38 months [78].

*Staged oral mucosa graft urethroplasty:* today, staged reconstructions using oral mucosal grafts has become a reliable and the most popular procedure to treat difficult anterior urethral strictures that are not amenable to single-stage graft or flap reconstructions. The indications are similar to the procedures described above. The surgical technique is generally similar (to variants) and based on the technique used for the Johanson and Schreiter's operations, that is, urethral marsupialization in the first stage followed by urethral tubularization 4–6 months later, the OMG being placed at the first stage. At times, it may be necessary to use additional grafts at the time of tubularization to optimize the urethral plate. This is the procedure of choice for strictures associated with LS. Success rates are very good when compared to earlier techniques with an acceptable number of surgical revisions. Multistage urethroplasty should replace "two-stage" urethroplasty as the accepted terminology as it is not uncommon for patients to require more than two procedures to complete

**97**

**Figure 21.**

*Historical Perspective and Innovations in Penile Urethroplasty*

successful tubularization. This may lead to more realistic patient expectations as well. Although completion of the second stage may not always be necessary for functional improvement, cosmetic outcomes with restoration of a glanular meatus can be excellent and achieved in the majority of patients [79]. An algorithm of surgical reconstruction of strictures of the meatus, fossa navicularis, and penile

**Tissue engineering, stem cell, and future:** the field of tissue engineering and scar modulation is an exciting area of research in reconstructive urology and is rapidly progressing. Much research has been devoted to the development of a tissue-engineered urethral graft. Currently used grafts, when long, can cause initial donor site morbidity or may be insufficient. Researchers have investigated cell-free and cell-seeded grafts as substitutes for human urethra. There are different approaches to developing these grafts with variable reported successes in studies conducted in animal and human models. Further research may improve the management of long and complex urethral strictures that usually require oral mucosa substitution of urethroplasty with tissue-engineered grafts. These grafts have become necessary because the use of oral mucosa may be limited by its availability. A combination of buccal (cheek), lingual (tongue), and labial (lip) mucosa may be utilized and necessary in some cases. Patients with reduced mouth opening or previous oral surgery may have less oral tissue for use. In addition, longer grafts carry a greater morbidity. The risk of donor site morbidity is increased in smokers, tobacco chewers, and those with poor oral hygiene, which will contraindicate the use of oral mucosa, and, therefore, necessitate a tissue-

To generate new tissues, biomedical engineering investigators have utilized three basic tools: cells, scaffold, and growth factor. The earliest use of human cells dates back to approximately 30 years ago [81]. Several different tissue-engineered grafts have been used for urethral reconstruction. There are two types of urethral grafts: (1) those that contain living autologous cells and (2) those that are cell free. The latter include grafts obtained from cadaveric or animal sources. This tissue undergoes treatment to become completely cell free. The resultant biological

*Algorithm of surgical reconstruction of strictures of the meatus, fossa navicularis, and penile urethral shaft. FN = fossa navicularis, LS = lichen sclerosus, TIP = tubularized incised plate, and OMG = oral mucosal graft.*

*DOI: http://dx.doi.org/10.5772/intechopen.85908*

urethral shaft is suggested (**Figure 21**).

engineered graft [80].

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

electrical dermatome and is meshed with a mechanical skin mesher using a 1:15 ratio sheet. The graft is placed on the wound ground lateral to the preserved urethral plate (**Figure 20**). The graft is fixed by running 5–0 monofilament sutures. The second stage (urethral tubularization) is performed in a standard fashion. In a study by Carr et al., success was achieved in 80% at a median follow-up of

*Mesh graft urethroplasty as described by Schreiter. Meshed skin graft has been placed on the wound ground and quilted to the host bed (first stage). The prepared urethral plate is tubularized approximately 6 months later* 

*Staged oral mucosa graft urethroplasty:* today, staged reconstructions using oral mucosal grafts has become a reliable and the most popular procedure to treat difficult anterior urethral strictures that are not amenable to single-stage graft or flap reconstructions. The indications are similar to the procedures described above. The surgical technique is generally similar (to variants) and based on the technique used for the Johanson and Schreiter's operations, that is, urethral marsupialization in the first stage followed by urethral tubularization 4–6 months later, the OMG being placed at the first stage. At times, it may be necessary to use additional grafts at the time of tubularization to optimize the urethral plate. This is the procedure of choice for strictures associated with LS. Success rates are very good when compared to earlier techniques with an acceptable number of surgical revisions. Multistage urethroplasty should replace "two-stage" urethroplasty as the accepted terminology as it is not uncommon for patients to require more than two procedures to complete

**96**

38 months [78].

**Figure 20.**

*(second stage).*

successful tubularization. This may lead to more realistic patient expectations as well. Although completion of the second stage may not always be necessary for functional improvement, cosmetic outcomes with restoration of a glanular meatus can be excellent and achieved in the majority of patients [79]. An algorithm of surgical reconstruction of strictures of the meatus, fossa navicularis, and penile urethral shaft is suggested (**Figure 21**).

**Tissue engineering, stem cell, and future:** the field of tissue engineering and scar modulation is an exciting area of research in reconstructive urology and is rapidly progressing. Much research has been devoted to the development of a tissue-engineered urethral graft. Currently used grafts, when long, can cause initial donor site morbidity or may be insufficient. Researchers have investigated cell-free and cell-seeded grafts as substitutes for human urethra. There are different approaches to developing these grafts with variable reported successes in studies conducted in animal and human models. Further research may improve the management of long and complex urethral strictures that usually require oral mucosa substitution of urethroplasty with tissue-engineered grafts. These grafts have become necessary because the use of oral mucosa may be limited by its availability. A combination of buccal (cheek), lingual (tongue), and labial (lip) mucosa may be utilized and necessary in some cases. Patients with reduced mouth opening or previous oral surgery may have less oral tissue for use. In addition, longer grafts carry a greater morbidity. The risk of donor site morbidity is increased in smokers, tobacco chewers, and those with poor oral hygiene, which will contraindicate the use of oral mucosa, and, therefore, necessitate a tissueengineered graft [80].

To generate new tissues, biomedical engineering investigators have utilized three basic tools: cells, scaffold, and growth factor. The earliest use of human cells dates back to approximately 30 years ago [81]. Several different tissue-engineered grafts have been used for urethral reconstruction. There are two types of urethral grafts: (1) those that contain living autologous cells and (2) those that are cell free. The latter include grafts obtained from cadaveric or animal sources. This tissue undergoes treatment to become completely cell free. The resultant biological

#### **Figure 21.**

*Algorithm of surgical reconstruction of strictures of the meatus, fossa navicularis, and penile urethral shaft. FN = fossa navicularis, LS = lichen sclerosus, TIP = tubularized incised plate, and OMG = oral mucosal graft.*

matrix is then implanted. A good vascular bed is needed to allow take and infiltration of host cells. As a rule, these techniques would only be expected to be particularly successful for substituting short urethral defects. In contrast, cellularized grafts contain a matrix populated with autologous cells, which are obtained from a small biopsy from the patient. The cells are cultured, expanded, and seeded onto the matrix. The matrix containing cells is then implanted onto the host bed [82].

A critical element required for successful tissue engineering is the cell source. Cells can be isolated from autologous urine-derived stems cells, smooth muscle cells, adipogenic, chondrogenic, and neural lineages [83]. Because simple cell injection to a target site is rarely feasible, a scaffold, or a template, also called artificial extracellular matrix, is necessary. The major function of a scaffold is to assist proliferation, differentiation, and biosynthesis of cells [84, 85].

Scar modulation represents another potential development that may revolutionize urethral reconstruction. Antifibrotic injectables, acting as scar inhibitors, may be placed into the stricture after stricturotomy. Stents impregnated with tacrolimus or paclitaxel have been tried in animal and human models with apparently promising early results [86, 87].

Regenerative medicine (cell therapy and tissue engineering) has made solid progress over the last three decades. We cautiously hope that these technologies will finally enter the routine clinical environment and be applicable in the treatment of urethral strictures/stenosis.

**Sexual impact of anterior urethroplasty:** overall, anterior urethroplasty appears to have minimal or no impact on long-term sexual dysfunction. One study revealed a moderate effect on sexual function, especially transient chordee in 25% of patients [88]. In another study, the impact of urethroplasty was not worse than circumcision [89]. Another study found a minimal impact on ejaculatory function [90]. One further study reported erectile dysfunction (ED) in approximately 40% of patients, although recovery occurred in most by 6 months. In this study, bulbar urethroplasty affected erectile function more than penile urethroplasty, probably explained by the proximity of the bulbar urethra to the erectile nerves [89]. Even staged urethroplasty does not seem to influence sexual function in patients undergoing penile urethroplasty, although many may experience *de novo* penile curvature, reduced penile length, and/or reduced penile sensitivity [91]. In conclusion, a meta-analysis conducted by Blaschko et al. found that the risk of *de novo* ED after anterior urethroplasty was low at 1% with most of the cases of the *de novo* ED resolving within 6–12 months; however, the possibility of *de novo* posturethroplasty ED, even if transient from the psychological impact of surgery or during revascularization, should be discussed during preoperative evaluation [92].

#### **8. Lower urinary tract symptoms (LUTS) and urethral strictures**

The spectrum of lower urinary tract symptoms (LUTS) at initial presentation for urethral stricture disease (USD) is well described. Anterior urethral stricture disease most commonly presents as urinary obstruction and may occasionally present as acute urinary retention. However, there is little data addressing these symptoms in patients after urethroplasty. LUTS after urethroplasty for anterior USD and the relationship of these symptoms to USD recurrence has also been observed [93]. It was reported that men with a successful outcome after urethroplasty tend to remain asymptomatic, whereas those who recur have LUTS, typically with weak urinary flow but without dysuria and hematuria. The authors supported

**99**

disease.

*Historical Perspective and Innovations in Penile Urethroplasty*

the need for a USD-specific validated questionnaire to be used for follow-up after

All men being evaluated for lower urinary tract symptoms (LUTS) should include urethral stricture in the differential diagnosis and include a combination of patient-reported symptom measures, uroflowmetry to assess severity of obstruction, and postvoid residual volume by ultrasound to determine degree of urinary retention. Patients with urethral stricture typically present a weak flow rate. However, evaluation of urethral stricture requires further specific testing to delineate the location, length of the stricture, and degree of narrowing such as urethroscopy and retrograde urethrogram with or without voiding cystourethrogram. LUTS are the usual clinical manifestation of urethral strictures, regardless of location, etiology, and severity. However, LUTS after urethral stricture repair are not uncommon. Urgency has been reported in 40% of men and urge incontinence in 12% of men after anterior urethroplasty. De novo urgency and urge incontinence is seen in 9 and 5% of men, respectively, after urethroplasty. Once a complication of urethroplasty (such as recurrent urethral stricture or diverticulum) has been excluded as a cause, evaluation of LUTS in such patients should focus on the differential diagnosis between bladder dysfunction (overactive bladder and underactive bladder) and other outlet obstructions (such as benign prostatic obstruction), dysfunctional voiding, or medical causes (such as nocturnal polyuria). Management of overactive bladder has different treatment options, which may include behavioral modification, physical therapy, anticholinergic, and/or beta-3 agonist medications. In more severe cases, intravesical onabotulinum toxin, sacral neuromodulation, or peripheral tibial nerve stimulation may be indicated. Definitive treatment for underactive bladder is limited in number and success. Although management of LUTS for patients after urethral stricture repair can usually proceed similarly as for patients without prior history of urethral reconstruction, special consideration and alterations in management need to be made when instrumenting the urethra, as the urethral lumen may be narrower in

Recently, an analysis of risk factors leading to postoperative urethral stricture and bladder neck contracture (BNC) following transurethral resection of prostate (TURP) has been performed [94]. The authors have found that lower resection speed, intraoperative urethral mucosal rupture, and postoperative continuous infection were associated with a higher risk of urethral stricture, whereas more severe storage symptoms and smaller prostate volumes were associated with a

Penile urethroplasty has evolved significantly over the last eight decades, since the first attempts at reconstruction using preputial tubes or a staged approach using penile skin [95]. An improved understanding of the pathophysiology of LS and a high complication rate following skin-based reconstructions favored a shift to the use of oral mucosal grafts, particularly in LS strictures. To date, very little advances have been achieved with conservative/pharmacological therapeutic options to stabilize or modulate the scarring process of this recalcitrant cutaneous

Currently, one of the critical limitations of penile urethroplasty is the common need for a staged reconstruction with all the inconveniences for the patient, and a 20–31% incidence of graft failure following the first stage, which leads to further

*DOI: http://dx.doi.org/10.5772/intechopen.85908*

urethroplasty.

these patients.

higher risk of BNC after TURP.

**9. Future directions and goals**

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

proliferation, differentiation, and biosynthesis of cells [84, 85].

ing early results [86, 87].

urethral strictures/stenosis.

preoperative evaluation [92].

matrix is then implanted. A good vascular bed is needed to allow take and infiltration of host cells. As a rule, these techniques would only be expected to be particularly successful for substituting short urethral defects. In contrast, cellularized grafts contain a matrix populated with autologous cells, which are obtained from a small biopsy from the patient. The cells are cultured, expanded, and seeded onto the matrix. The matrix containing cells is then implanted onto the host bed [82]. A critical element required for successful tissue engineering is the cell source. Cells can be isolated from autologous urine-derived stems cells, smooth muscle cells, adipogenic, chondrogenic, and neural lineages [83]. Because simple cell injection to a target site is rarely feasible, a scaffold, or a template, also called artificial extracellular matrix, is necessary. The major function of a scaffold is to assist

Scar modulation represents another potential development that may revolutionize urethral reconstruction. Antifibrotic injectables, acting as scar inhibitors, may be placed into the stricture after stricturotomy. Stents impregnated with tacrolimus or paclitaxel have been tried in animal and human models with apparently promis-

Regenerative medicine (cell therapy and tissue engineering) has made solid progress over the last three decades. We cautiously hope that these technologies will finally enter the routine clinical environment and be applicable in the treatment of

**Sexual impact of anterior urethroplasty:** overall, anterior urethroplasty appears to have minimal or no impact on long-term sexual dysfunction. One study revealed a moderate effect on sexual function, especially transient chordee in 25% of patients [88]. In another study, the impact of urethroplasty was not worse than circumcision [89]. Another study found a minimal impact on ejaculatory function [90]. One further study reported erectile dysfunction (ED) in approximately 40% of patients, although recovery occurred in most by 6 months. In this study, bulbar urethroplasty affected erectile function more than penile urethroplasty, probably explained by the proximity of the bulbar urethra to the erectile nerves [89]. Even staged urethroplasty does not seem to influence sexual function in patients undergoing penile urethroplasty, although many may experience *de novo* penile curvature, reduced penile length, and/or reduced penile sensitivity [91]. In conclusion, a meta-analysis conducted by Blaschko et al. found that the risk of *de novo* ED after anterior urethroplasty was low at 1% with most of the cases of the *de novo* ED resolving within 6–12 months; however, the possibility of *de novo* posturethroplasty ED, even if transient from the psychological impact of surgery or during revascularization, should be discussed during

**8. Lower urinary tract symptoms (LUTS) and urethral strictures**

The spectrum of lower urinary tract symptoms (LUTS) at initial presentation for urethral stricture disease (USD) is well described. Anterior urethral stricture disease most commonly presents as urinary obstruction and may occasionally present as acute urinary retention. However, there is little data addressing these symptoms in patients after urethroplasty. LUTS after urethroplasty for anterior USD and the relationship of these symptoms to USD recurrence has also been observed [93]. It was reported that men with a successful outcome after urethroplasty tend to remain asymptomatic, whereas those who recur have LUTS, typically with weak urinary flow but without dysuria and hematuria. The authors supported

**98**

the need for a USD-specific validated questionnaire to be used for follow-up after urethroplasty.

All men being evaluated for lower urinary tract symptoms (LUTS) should include urethral stricture in the differential diagnosis and include a combination of patient-reported symptom measures, uroflowmetry to assess severity of obstruction, and postvoid residual volume by ultrasound to determine degree of urinary retention. Patients with urethral stricture typically present a weak flow rate. However, evaluation of urethral stricture requires further specific testing to delineate the location, length of the stricture, and degree of narrowing such as urethroscopy and retrograde urethrogram with or without voiding cystourethrogram. LUTS are the usual clinical manifestation of urethral strictures, regardless of location, etiology, and severity. However, LUTS after urethral stricture repair are not uncommon. Urgency has been reported in 40% of men and urge incontinence in 12% of men after anterior urethroplasty. De novo urgency and urge incontinence is seen in 9 and 5% of men, respectively, after urethroplasty. Once a complication of urethroplasty (such as recurrent urethral stricture or diverticulum) has been excluded as a cause, evaluation of LUTS in such patients should focus on the differential diagnosis between bladder dysfunction (overactive bladder and underactive bladder) and other outlet obstructions (such as benign prostatic obstruction), dysfunctional voiding, or medical causes (such as nocturnal polyuria). Management of overactive bladder has different treatment options, which may include behavioral modification, physical therapy, anticholinergic, and/or beta-3 agonist medications. In more severe cases, intravesical onabotulinum toxin, sacral neuromodulation, or peripheral tibial nerve stimulation may be indicated. Definitive treatment for underactive bladder is limited in number and success. Although management of LUTS for patients after urethral stricture repair can usually proceed similarly as for patients without prior history of urethral reconstruction, special consideration and alterations in management need to be made when instrumenting the urethra, as the urethral lumen may be narrower in these patients.

Recently, an analysis of risk factors leading to postoperative urethral stricture and bladder neck contracture (BNC) following transurethral resection of prostate (TURP) has been performed [94]. The authors have found that lower resection speed, intraoperative urethral mucosal rupture, and postoperative continuous infection were associated with a higher risk of urethral stricture, whereas more severe storage symptoms and smaller prostate volumes were associated with a higher risk of BNC after TURP.

#### **9. Future directions and goals**

Penile urethroplasty has evolved significantly over the last eight decades, since the first attempts at reconstruction using preputial tubes or a staged approach using penile skin [95]. An improved understanding of the pathophysiology of LS and a high complication rate following skin-based reconstructions favored a shift to the use of oral mucosal grafts, particularly in LS strictures. To date, very little advances have been achieved with conservative/pharmacological therapeutic options to stabilize or modulate the scarring process of this recalcitrant cutaneous disease.

Currently, one of the critical limitations of penile urethroplasty is the common need for a staged reconstruction with all the inconveniences for the patient, and a 20–31% incidence of graft failure following the first stage, which leads to further

revision(s) prior to the final tubularization [95]. Insufficient oral mucosal grafts for panurethral stricture reconstruction, especially in redo cases, add serious problems.

Considerable research has been done in the areas of biomaterials, regenerative medicine, including scar modulation, and tissue engineering to overcome the limitations of current penile urethral stricture management. These experimental technologies appear exciting, revolutionary, and ripe with potential. The main goals of these research areas would be to produce scar inhibitors that might be placed into the stricture after urethrotomy, on the one hand, and to generate an ideal biomaterial in unlimited quantities, easily cultured in laboratory, readily available "off the shelf" and without the morbidity associated with graft harvesting, on the other hand. Unfortunately, we are not quite there yet.

#### **10. Conclusion**

The surgical treatment of penile urethral stricture is continually evolving. No one technique is appropriate for all situations, and the successful reconstructive urologist needs to be comfortable with a repertoire of different, versatile techniques in order to best treat each individual patient's problem. Since the early 1990s, OMG was introduced in urethral reconstructive surgery and has become the first choice of most urethral surgeons.

Although all are grouped as anterior urethral strictures, penile urethral strictures are different from bulbar urethral strictures. Flaps are still preferred to grafts in long, recurrent penile urethral strictures by some surgeons. Recently, one-stage dorsal OMG urethroplasty via perineal approach has been suggested for the management of most strictures of the penile shaft urethra with both good functional and remarkable cosmetic outcomes. However, in patients who have experienced failed hypospadias repair or in whom the penile skin and urethral plate are not suitable for urethroplasty, two-stage (usually multistage) urethroplasty is recommended. Management of some lengthy, complex strictures remains a great challenge even for experienced reconstructive surgeons. Staged urethroplasty, such as the Johanson's technique with or without the use of grafts, is still a good surgical option. Regenerative medicine continues to show promise, but further investigation is needed to reach clinical application in the future. All in all, these great improvements in penile urethral surgical technique should lead to optimization of the surgical treatment algorithm.

**101**

**Author details**

Francisco E. Martins1

provided the original work is properly cited.

University of Lisbon, Lisbon, Portugal

2 Urology Unit, ULSNA, Portalegre, Portugal

\*Address all correspondence to: faemartins@gmail.com

*Historical Perspective and Innovations in Penile Urethroplasty*

*DOI: http://dx.doi.org/10.5772/intechopen.85908*

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

and Natalia M. Martins2

\*, Pedro Simoes de Oliveira1

1 Department of Urology, School of Medicine, Santa Maria Hospital/CHULN,

*Historical Perspective and Innovations in Penile Urethroplasty DOI: http://dx.doi.org/10.5772/intechopen.85908*

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

hand. Unfortunately, we are not quite there yet.

problems.

**10. Conclusion**

of most urethral surgeons.

surgical treatment algorithm.

revision(s) prior to the final tubularization [95]. Insufficient oral mucosal grafts for panurethral stricture reconstruction, especially in redo cases, add serious

Considerable research has been done in the areas of biomaterials, regenerative medicine, including scar modulation, and tissue engineering to overcome the limitations of current penile urethral stricture management. These experimental technologies appear exciting, revolutionary, and ripe with potential. The main goals of these research areas would be to produce scar inhibitors that might be placed into the stricture after urethrotomy, on the one hand, and to generate an ideal biomaterial in unlimited quantities, easily cultured in laboratory, readily available "off the shelf" and without the morbidity associated with graft harvesting, on the other

The surgical treatment of penile urethral stricture is continually evolving. No one technique is appropriate for all situations, and the successful reconstructive urologist needs to be comfortable with a repertoire of different, versatile techniques in order to best treat each individual patient's problem. Since the early 1990s, OMG was introduced in urethral reconstructive surgery and has become the first choice

Although all are grouped as anterior urethral strictures, penile urethral strictures are different from bulbar urethral strictures. Flaps are still preferred to grafts in long, recurrent penile urethral strictures by some surgeons. Recently, one-stage dorsal OMG urethroplasty via perineal approach has been suggested for the management of most strictures of the penile shaft urethra with both good functional and remarkable cosmetic outcomes. However, in patients who have experienced failed hypospadias repair or in whom the penile skin and urethral plate are not suitable for urethroplasty, two-stage (usually multistage) urethroplasty is recommended. Management of some lengthy, complex strictures remains a great challenge even for experienced reconstructive surgeons. Staged urethroplasty, such as the Johanson's technique with or without the use of grafts, is still a good surgical option. Regenerative medicine continues to show promise, but further investigation is needed to reach clinical application in the future. All in all, these great improvements in penile urethral surgical technique should lead to optimization of the

**100**

### **Author details**

Francisco E. Martins1 \*, Pedro Simoes de Oliveira1 and Natalia M. Martins2

1 Department of Urology, School of Medicine, Santa Maria Hospital/CHULN, University of Lisbon, Lisbon, Portugal

2 Urology Unit, ULSNA, Portalegre, Portugal

\*Address all correspondence to: faemartins@gmail.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

### **References**

[1] Velasquez EF, Barreto JE, Cold CJ, Cubilla AL, et al. Penis and distal urethra. In: Mills SE, editor. Histology for Pathologists. Vol. 3. Philadelphia: Lippincott Williams and Wilkins; 2007. pp. 983-997

[2] Dagrosa LM, Gormley A. Anatomy of the urethra. In: Keane TE, Graham SD, editors. Glenn's Urologic Surgery. 8th ed. Philadelphia: Wolters Kluwer; 2016. pp. 311-314

[3] Fenton AS, Morey AF, Aviles R, et al. Anterior urethral strictures: Etiology and characteristics. Urology. 2005;**65**:1055-1058

[4] Lumen N, Hoebeke P, Willemsen P. Etiology of urethral stricture in the 21st century. The Journal of Urology. 2009;**182**:983-987

[5] Palminteri E, Berdondini E, Verze P, Nunzio CD, Vitarelli A, Carmignani L. Contemporary urethral stricture characteristic in the developed world. Urology. 2013;**81**:190-197

[6] Barbagli G, Lazzeri M, Palminteri E, Turini D. Lichen sclerosus of male genitalia involving anterior urethra. Lancet. 1999;**354**:429

[7] Pugliese JM, Morey AF, Peteron AC. Lichen sclerosus: Review of the literature and current recommendations for management. The Journal of Urology. 2007;**178**:2268-2276

[8] Elliott S, Brandes SB. Etiology, histology and classification of urethral stricture disease. In: Brandes SB, Morey AF, editors. Advanced Male Urethral and Genital Reconstructive Surgery. 2nd ed. NY: Humana Press; 2014. pp. 95-102

[9] Nuss GR, Granieri MA, Zhao LC. Presenting symptoms of anterior

urethral stricture disease: A disease specific, patient reported questionnaire to measure outcomes. The Journal of Urology. 2012;**187**:559-562

[10] El-Ghar MA, Osman Y, Elbaz E, El-Diasty T. MR urethrogram versus combined retrograde urethrogram and sonourethrography in diagnosis of urethral stricture. European Journal of Radiology. 2010;**74**:193-198

[11] McAninch JW, Laing FC, Jeffrey RB Jr. Sonourethrography in the evaluation of the urethral strictures: A preliminary report. The Journal of Urology. 1988;**139**:294-297

[12] Nash PA, McAninch JW, Bruce JE. Sonourethrography in the evaluation of anterior urethral strictures. The Journal of Urology. 1995;**154**:72-76

[13] Sachse H. Treatment of urethral stricture: Transurethral slit in view using sharp section. Fortschritte der Medizin. 1974;**92**:12-15

[14] Steenkamp JW, Heyns CF, de Kock M. Internal urethrotomy versus dilatation ass treatment for male urethral strictures: A prospective, randomized comparison. The Journal of Urology. 1997;**157**:98-101

[15] Dubey D. The current role of direct vision internal urethrotomy and selfcatheterization for anterior urethral strictures. Indian Journal of Urology. 2011;**27**:392-396

[16] Heyns CF, Steenkamp JW, de Kock ML, Whitaker P. Treatment of male urethral strictures: Is repeated dilatation or internal urethrotomy useful? The Journal of Urology. 1998;**160**:356-358

[17] Pansadoro V, Emiliozzi P. Internal urethrotomy in the management of anterior urethral strictures: Long-term

**103**

*Historical Perspective and Innovations in Penile Urethroplasty*

overview. International Brazilian Journal of Urology. 2012;**38**:307-316

2001;**88**:385-389

1998;**16**:181-185

2002;**29**:381-387

2003;**169**:1754-1757

1996;**48**:194-198

[27] Andrich DE, Leach CJ, Mundy AR. The Barbagli procedure gives the best results for patch urethroplasty of the bulbar urethra. BJU International.

[28] Iselin CE, Webster GD. Dorsal onlay urethroplasty for urethral stricture repair. World Journal of Urology.

[29] Wessells H. Ventral onlay graft techniques for urethroplasty. The Urologic Clinics of North America.

[30] Elliot SP, Metro MJ, McAninch JW. Long-term follow-up of the ventrally placed buccal mucosa onlay graft in bulbar urethral

reconstruction. The Journal of Urology.

[31] Morey AF, McAninch JW. When and how to use buccal mucosal grafts in adult bulbar urethroplasty. Urology.

[32] Blandy JP, Singh M, Notley RG, Treidder GC. The results and complications of scrotal-flap urethroplasty for stricture. British Journal of Urology. 1971;**43**:52-57

urethroplasty. The Journal of Urology.

[35] Gil-Vernet A, Arango O, Gil-Vernet J Jr, Gelabert-Mas A, Gil-Vernet J. Scrotal flap epilation in urethroplasty: Concepts and technique. The Journal of Urology.

[34] Provet JA. Scrotal island flap urethroplasty in the management of bulbar urethral strictures. The Journal of Urology. 1989;**142**(6):1455-1457

[33] Yachia D. A new, onestage pedicled scrotal kin graft

1986;**136**(3):589-592

1995;**154**(5):1723-1726

*DOI: http://dx.doi.org/10.5772/intechopen.85908*

Urethrotomy has a much lower success rate than previously reported. The Journal of Urology. 2010;**183**:1859-1862

[19] Naudé AM, Heyns CF. What is the place of internal urethrotomy in the treatment of urethral stricture disease? Nature Clinical Practice. Urology.

[20] Gallegos MA, Santucci RA. Advances in urethral stricture management. F1000Research.

10.12688/f1000reearch.9741.1

[21] Jin T, Ki H, Jiang L-H Wang L, Wang K-J. Safety and efficacy of laser and cold knife urethrotomy for urethral stricture. Chinese Medical Journal.

2016;**5**(F10000Faculty Rev):2913. DOI:

[22] Bürger RA et al. The buccal mucosa graft for urethral reconstruction: A preliminary report. The Journal of

[23] Dessanti A, Rigamonti W, Merulla V, Falchetti D, Caccia G. Autologous buccal mucosa graft for hypospadia repair: An initial report. The Journal of

[24] Lumen N, Oosterlinck W, Hoebeke P. Urethral reconstruction using buccal mucosa or penile skin grafts: Systematic review and meta-analysis. Urologia Internationalis. 2012;**89**:387-394

[25] Markiewicz MR et al. The oral mucosa graft: A systematic review. The Journal of Urology. 2007;**178**:387-394

Romano G, Lazzeri M. Current

[26] Barbagli G, Sansalone S, Djinovic R,

controversies in reconstructive surgery of the anterior urethra: A clinical

follow-up. The Journal of Urology.

[18] Santucci R, Eisenberg L.

1996;**156**:73-75

2005;**2**(11):538-545

2010;**123**:1589-1595

Urology. 1992;**147**:662-664

Urology. 1992;**147**:1081-1084

*Historical Perspective and Innovations in Penile Urethroplasty DOI: http://dx.doi.org/10.5772/intechopen.85908*

follow-up. The Journal of Urology. 1996;**156**:73-75

[18] Santucci R, Eisenberg L. Urethrotomy has a much lower success rate than previously reported. The Journal of Urology. 2010;**183**:1859-1862

[19] Naudé AM, Heyns CF. What is the place of internal urethrotomy in the treatment of urethral stricture disease? Nature Clinical Practice. Urology. 2005;**2**(11):538-545

[20] Gallegos MA, Santucci RA. Advances in urethral stricture management. F1000Research. 2016;**5**(F10000Faculty Rev):2913. DOI: 10.12688/f1000reearch.9741.1

[21] Jin T, Ki H, Jiang L-H Wang L, Wang K-J. Safety and efficacy of laser and cold knife urethrotomy for urethral stricture. Chinese Medical Journal. 2010;**123**:1589-1595

[22] Bürger RA et al. The buccal mucosa graft for urethral reconstruction: A preliminary report. The Journal of Urology. 1992;**147**:662-664

[23] Dessanti A, Rigamonti W, Merulla V, Falchetti D, Caccia G. Autologous buccal mucosa graft for hypospadia repair: An initial report. The Journal of Urology. 1992;**147**:1081-1084

[24] Lumen N, Oosterlinck W, Hoebeke P. Urethral reconstruction using buccal mucosa or penile skin grafts: Systematic review and meta-analysis. Urologia Internationalis. 2012;**89**:387-394

[25] Markiewicz MR et al. The oral mucosa graft: A systematic review. The Journal of Urology. 2007;**178**:387-394

[26] Barbagli G, Sansalone S, Djinovic R, Romano G, Lazzeri M. Current controversies in reconstructive surgery of the anterior urethra: A clinical

overview. International Brazilian Journal of Urology. 2012;**38**:307-316

[27] Andrich DE, Leach CJ, Mundy AR. The Barbagli procedure gives the best results for patch urethroplasty of the bulbar urethra. BJU International. 2001;**88**:385-389

[28] Iselin CE, Webster GD. Dorsal onlay urethroplasty for urethral stricture repair. World Journal of Urology. 1998;**16**:181-185

[29] Wessells H. Ventral onlay graft techniques for urethroplasty. The Urologic Clinics of North America. 2002;**29**:381-387

[30] Elliot SP, Metro MJ, McAninch JW. Long-term follow-up of the ventrally placed buccal mucosa onlay graft in bulbar urethral reconstruction. The Journal of Urology. 2003;**169**:1754-1757

[31] Morey AF, McAninch JW. When and how to use buccal mucosal grafts in adult bulbar urethroplasty. Urology. 1996;**48**:194-198

[32] Blandy JP, Singh M, Notley RG, Treidder GC. The results and complications of scrotal-flap urethroplasty for stricture. British Journal of Urology. 1971;**43**:52-57

[33] Yachia D. A new, onestage pedicled scrotal kin graft urethroplasty. The Journal of Urology. 1986;**136**(3):589-592

[34] Provet JA. Scrotal island flap urethroplasty in the management of bulbar urethral strictures. The Journal of Urology. 1989;**142**(6):1455-1457

[35] Gil-Vernet A, Arango O, Gil-Vernet J Jr, Gelabert-Mas A, Gil-Vernet J. Scrotal flap epilation in urethroplasty: Concepts and technique. The Journal of Urology. 1995;**154**(5):1723-1726

**102**

pp. 95-102

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

urethral stricture disease: A disease specific, patient reported questionnaire to measure outcomes. The Journal of

[10] El-Ghar MA, Osman Y, Elbaz E, El-Diasty T. MR urethrogram versus combined retrograde urethrogram and sonourethrography in diagnosis of urethral stricture. European Journal of

[11] McAninch JW, Laing FC, Jeffrey RB Jr. Sonourethrography in the evaluation of the urethral strictures: A preliminary

[12] Nash PA, McAninch JW, Bruce JE. Sonourethrography in the evaluation of anterior urethral strictures. The Journal

[13] Sachse H. Treatment of urethral stricture: Transurethral slit in view using sharp section. Fortschritte der

[14] Steenkamp JW, Heyns CF, de Kock M. Internal urethrotomy versus dilatation ass treatment for male urethral strictures: A prospective, randomized comparison. The Journal of

[15] Dubey D. The current role of direct vision internal urethrotomy and selfcatheterization for anterior urethral strictures. Indian Journal of Urology.

[16] Heyns CF, Steenkamp JW, de Kock ML, Whitaker P. Treatment of male urethral strictures: Is repeated dilatation or internal urethrotomy useful? The Journal of Urology. 1998;**160**:356-358

[17] Pansadoro V, Emiliozzi P. Internal urethrotomy in the management of anterior urethral strictures: Long-term

Urology. 2012;**187**:559-562

Radiology. 2010;**74**:193-198

report. The Journal of Urology.

of Urology. 1995;**154**:72-76

Medizin. 1974;**92**:12-15

Urology. 1997;**157**:98-101

2011;**27**:392-396

1988;**139**:294-297

[1] Velasquez EF, Barreto JE, Cold CJ, Cubilla AL, et al. Penis and distal urethra. In: Mills SE, editor. Histology for Pathologists. Vol. 3. Philadelphia: Lippincott Williams and Wilkins; 2007.

[2] Dagrosa LM, Gormley A. Anatomy of the urethra. In: Keane TE, Graham SD, editors. Glenn's Urologic Surgery. 8th ed. Philadelphia: Wolters Kluwer; 2016.

[3] Fenton AS, Morey AF, Aviles R, et al. Anterior urethral strictures: Etiology and characteristics. Urology.

[4] Lumen N, Hoebeke P, Willemsen P. Etiology of urethral stricture in the 21st century. The Journal of Urology.

[5] Palminteri E, Berdondini E, Verze P, Nunzio CD, Vitarelli A, Carmignani L. Contemporary urethral stricture characteristic in the developed world.

[6] Barbagli G, Lazzeri M, Palminteri E, Turini D. Lichen sclerosus of male genitalia involving anterior urethra.

[7] Pugliese JM, Morey AF, Peteron AC. Lichen sclerosus: Review of the literature and current recommendations

for management. The Journal of Urology. 2007;**178**:2268-2276

[8] Elliott S, Brandes SB. Etiology, histology and classification of urethral stricture disease. In: Brandes SB, Morey AF, editors. Advanced Male Urethral and Genital Reconstructive Surgery. 2nd ed. NY: Humana Press; 2014.

[9] Nuss GR, Granieri MA, Zhao LC. Presenting symptoms of anterior

pp. 983-997

**References**

pp. 311-314

2005;**65**:1055-1058

2009;**182**:983-987

Urology. 2013;**81**:190-197

Lancet. 1999;**354**:429

[36] Gil-Vernet J, Arango O, Gil-Vernet A, Gil-Vernet J Jr, Gelabert-Mas A. A new biaxial epilated scrotal flap for reconstructive urethral surgery. The Journal of Urology. 1997;**158**(2):412-420

[37] Orandi A. One-stage urethroplasty: 4-Year follow-up. The Journal of Urology. 1972;**107**(6):717-719

[38] Quartey KM. One-stage penile/ preputial island flap urethroplasty for urethral stricture. The Journal of Urology. 1985;**134**(3):474-475

[39] McAninch JW. Reconstruction of extensive urethral strictures: Circular fasciocutaneous penile flap. The Journal of Urology. 1993;**149**(3):488-491

[40] Johanson B. Reconstruction of the male urethra in strictures. Application of the buried intact epithelium technique. Acta Chirurgica Scandinavica. 1953;**176**(Suppl. 176): 1-89

[41] Bracka A. Hypospadias repair: The two-stage alternative. British Journal of Urology. 1995;**76**(Suppl. 3):31-41

[42] Bracka A. A versatile two-stage hypospadias repair. British Journal of Plastic Surgery. 1995;**48**:345-352

[43] Bracka A. The role of two-stage repair in modern hypospadiology. Indian Journal of Urology. 2008;**24**:210-218

[44] Devine CJ, Franz JP, Horton CE. Evaluation and treatment of patients with failed hypospadias repair. The Journal of Urology. 1978;**119**:223-226

[45] Stecker JF, Horton CE, Devine CJ, McCraw JB. Hypospadias cripples. The Urologic Clinics of North America. 1981;**8**:539-544

[46] Barbagli G, De Angelis M, Palminteri E, Lazzeri M. Failed hypospadias repair presenting in adults. European Urology. 2006;**49**:887-895

[47] Tang S-H, Hammer CC, Doumanian L, Santucci RA. Adult urethral stricture disease after childhood hypospadias repair. Advances in Urology. 2008:150315. DOI: 10.1155/2008/150315

[48] Malone P. A new technique for meatal stenosis in patients with lichen sclerosus. The Journal of Urology. 2004;**172**:949-952

[49] Navalón P, Ramada C, Ordono F, Pallas Y, Monllor ME. Long-term follow-up of malone meatoplasty for meatal stenosis in patients with lichen sclerosus. Journal of Anesthesia and Surgery. 2016;**4**(2):121-124

[50] Cohney BC. A penile flap procedure for the relief of meatal strictures. British Journal of Urology. 1963;**35**:182-183

[51] Blandy JP, Tresider GC. Meatoplasty. British Journal of Urology. 1967;**39**:633-634

[52] Brannen GE. Meatal reconstruction. The Journal of Urology. 1976;**116**: 319-321

[53] De Sy WA. Aesthetic repair of meatal stricture. The Journal of Urology. 1984;**132**:678-679

[54] Jordan GH. Reconstruction of the fossa navicularis. The Journal of Urology. 1987;**138**:102-104

[55] Armenakas NA, Morey AF, McAninch JW. Reconstruction of the resistant strictures of the fossa navicularis and meatus. The Journal of Urology. 1998;**160**:359-363

[56] DeLong JM, Jordan GH. Reconstruction of the fossa navicularis. In: Smith JA Jr, Howards S, Preminger GM, Dmochowski RR, editors. Hinman's

**105**

*Historical Perspective and Innovations in Penile Urethroplasty*

with buccal graft urethral plate

2011;**186**(3):935-938

2009;**6**:533-538

pp. 571-594

of distal anterior urethral

reconstruction and simultaneous onlay penile skin flap. The Journal of Urology.

[66] Tonkin JB, Jordan GH. Management

strictures. Nature Reviews. Urology.

[67] Quartey JK. One-stage penile/ preputial cutaneous island flap urethroplasty for urethral stricture: A preliminary report. The Journal of Urology. 1983;**129**(2):284-287

[68] Quartey JK. One-stage penile/ preputial island flap urethroplasty for difficult posterior urethral strictures. World Journal of Urology. 1987;**5**:37-40

[69] Chapple C, Turner-Warwick. Substitution urethroplasty and the pedicle island skin procedure. In: McAninch JW, editor. Traumatic and Reconstructive Urology. Philadelphia: WB Saunders Company; 1996.

[70] Devine PC, Horton CE, Devine CJ Sr, et al. Use of full thickness skin grafts in repair of urethral strictures. The Journal of Urology. 1963;**90**:67-71

[71] Barbagli G, Pellegrini G, Corradini

[72] Martins FE, Oliveira T, Oliveira P, Felício J, Dave C, Martins NK. Perineal incision to repair penile urethral strictures is a versatile and cosmetic approach. In: Presented at the 37th Congress of the Societé Internationale d'Urologie; Lisbon, October 19-22. 2017

[73] Martins F, Kulkarni S, Joshi P, Marcelino J, de Oliveira TR, Oliveira P, et al. Kulkarni technique of perineal approach with penile inversion for

F, Montorsi F, Sansalone S, Butnaru B, et al. One-stage penile urethroplasty using oral mucosa graft and glue. European Urology.

2006;**70**(6):1069-1075

*DOI: http://dx.doi.org/10.5772/intechopen.85908*

[57] Devine CJ, Horton CE. A one stage hypospadias repair. Journal of Urology. 2002;**167**:1169-1174 (reprinted from J

Atlas of Urologic Surgery. 4th ed. Philadelphia: Elsevier; 2018. pp. 686-692

Urol, 85: 166-172, 1961)

1994;**151**(2):464-465

2001;**58**:657-659

1983;**130**(5):905-908

1998;**16**(3):171-174

2010;**24**(1):63-67

2012;**89**(1):116-119

[58] Snodgrass W. Tubularized, incised plate urethroplasty for distal hypospadias. The Journal of Urology.

[59] Asopa M, Garg M, Singhal GC, et al. Dorsal free graft urethroplasty for urethral stricture by ventral sagittal urethrotomy approach. Urology.

[61] Naudé JH. Endoscopic skin-graft urethroplasty. World Journal of Urology.

[62] Kuyumcuoglu U et al. Antegrade endourethroplasty with free skin graft for recurrent vesicourethral anastomotic strictures after radical prostatectomy. Journal of Endourology.

[63] Seth A, Saini AK, Dogra PN. Hybrid minimally invasive urethroplasty for pan-anterior urethral strictures: Initial results. Urologia Internationalis.

[64] Nikolavsky D, Abouelleil M, Daneshvar M. Transurethral ventral buccal mucosa graft inlay urethroplasty for reconstruction of fossa navicularis and distal urethral strictures: Surgical technique and preliminary results. International Urology and Nephrology.

2016;**48**:1823. DOI: 10.1007/

[65] Gelman J, Sohn W. One-stage repair of obliterative distal urethral strictures

s11255-016-1381-1

[60] Gaur DD. Endourethral urethroplasty—Use of a new catheter. The Journal of Urology. *Historical Perspective and Innovations in Penile Urethroplasty DOI: http://dx.doi.org/10.5772/intechopen.85908*

Atlas of Urologic Surgery. 4th ed. Philadelphia: Elsevier; 2018. pp. 686-692

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

hypospadias repair presenting in adults. European Urology. 2006;**49**:887-895

Advances in Urology. 2008:150315. DOI:

[48] Malone P. A new technique for meatal stenosis in patients with lichen sclerosus. The Journal of Urology.

[49] Navalón P, Ramada C, Ordono F, Pallas Y, Monllor ME. Long-term follow-up of malone meatoplasty for meatal stenosis in patients with lichen sclerosus. Journal of Anesthesia and

Surgery. 2016;**4**(2):121-124

British Journal of Urology.

[50] Cohney BC. A penile flap procedure for the relief of meatal strictures. British Journal of Urology.

[51] Blandy JP, Tresider GC. Meatoplasty.

[52] Brannen GE. Meatal reconstruction. The Journal of Urology. 1976;**116**:

[53] De Sy WA. Aesthetic repair of meatal stricture. The Journal of Urology.

[54] Jordan GH. Reconstruction of the fossa navicularis. The Journal of

[55] Armenakas NA, Morey AF, McAninch JW. Reconstruction of the resistant strictures of the fossa navicularis and meatus. The Journal of

Urology. 1987;**138**:102-104

Urology. 1998;**160**:359-363

[56] DeLong JM, Jordan GH.

 Reconstruction of the fossa navicularis. In: Smith JA Jr, Howards S, Preminger GM, Dmochowski RR, editors. Hinman's

[47] Tang S-H, Hammer CC, Doumanian L, Santucci RA. Adult urethral stricture disease after childhood hypospadias repair.

10.1155/2008/150315

2004;**172**:949-952

1963;**35**:182-183

1967;**39**:633-634

1984;**132**:678-679

319-321

[36] Gil-Vernet J, Arango O, Gil-Vernet A, Gil-Vernet J Jr, Gelabert-Mas A. A new biaxial epilated scrotal flap for reconstructive urethral surgery. The Journal of Urology. 1997;**158**(2):412-420

[37] Orandi A. One-stage urethroplasty:

4-Year follow-up. The Journal of Urology. 1972;**107**(6):717-719

[38] Quartey KM. One-stage penile/ preputial island flap urethroplasty for urethral stricture. The Journal of Urology. 1985;**134**(3):474-475

[39] McAninch JW. Reconstruction of extensive urethral strictures: Circular fasciocutaneous penile flap. The Journal

of Urology. 1993;**149**(3):488-491

[40] Johanson B. Reconstruction of the male urethra in strictures. Application of the buried intact epithelium technique. Acta Chirurgica Scandinavica. 1953;**176**(Suppl. 176):

[41] Bracka A. Hypospadias repair: The two-stage alternative. British Journal of Urology. 1995;**76**(Suppl. 3):31-41

[42] Bracka A. A versatile two-stage hypospadias repair. British Journal of Plastic Surgery. 1995;**48**:345-352

[43] Bracka A. The role of two-stage repair in modern hypospadiology.

[44] Devine CJ, Franz JP, Horton CE. Evaluation and treatment of patients with failed hypospadias repair. The Journal of Urology. 1978;**119**:223-226

[45] Stecker JF, Horton CE, Devine CJ, McCraw JB. Hypospadias cripples. The Urologic Clinics of North America.

[46] Barbagli G, De Angelis M, Palminteri E, Lazzeri M. Failed

Indian Journal of Urology.

2008;**24**:210-218

1981;**8**:539-544

1-89

**104**

[57] Devine CJ, Horton CE. A one stage hypospadias repair. Journal of Urology. 2002;**167**:1169-1174 (reprinted from J Urol, 85: 166-172, 1961)

[58] Snodgrass W. Tubularized, incised plate urethroplasty for distal hypospadias. The Journal of Urology. 1994;**151**(2):464-465

[59] Asopa M, Garg M, Singhal GC, et al. Dorsal free graft urethroplasty for urethral stricture by ventral sagittal urethrotomy approach. Urology. 2001;**58**:657-659

[60] Gaur DD. Endourethral urethroplasty—Use of a new catheter. The Journal of Urology. 1983;**130**(5):905-908

[61] Naudé JH. Endoscopic skin-graft urethroplasty. World Journal of Urology. 1998;**16**(3):171-174

[62] Kuyumcuoglu U et al. Antegrade endourethroplasty with free skin graft for recurrent vesicourethral anastomotic strictures after radical prostatectomy. Journal of Endourology. 2010;**24**(1):63-67

[63] Seth A, Saini AK, Dogra PN. Hybrid minimally invasive urethroplasty for pan-anterior urethral strictures: Initial results. Urologia Internationalis. 2012;**89**(1):116-119

[64] Nikolavsky D, Abouelleil M, Daneshvar M. Transurethral ventral buccal mucosa graft inlay urethroplasty for reconstruction of fossa navicularis and distal urethral strictures: Surgical technique and preliminary results. International Urology and Nephrology. 2016;**48**:1823. DOI: 10.1007/ s11255-016-1381-1

[65] Gelman J, Sohn W. One-stage repair of obliterative distal urethral strictures

with buccal graft urethral plate reconstruction and simultaneous onlay penile skin flap. The Journal of Urology. 2011;**186**(3):935-938

[66] Tonkin JB, Jordan GH. Management of distal anterior urethral strictures. Nature Reviews. Urology. 2009;**6**:533-538

[67] Quartey JK. One-stage penile/ preputial cutaneous island flap urethroplasty for urethral stricture: A preliminary report. The Journal of Urology. 1983;**129**(2):284-287

[68] Quartey JK. One-stage penile/ preputial island flap urethroplasty for difficult posterior urethral strictures. World Journal of Urology. 1987;**5**:37-40

[69] Chapple C, Turner-Warwick. Substitution urethroplasty and the pedicle island skin procedure. In: McAninch JW, editor. Traumatic and Reconstructive Urology. Philadelphia: WB Saunders Company; 1996. pp. 571-594

[70] Devine PC, Horton CE, Devine CJ Sr, et al. Use of full thickness skin grafts in repair of urethral strictures. The Journal of Urology. 1963;**90**:67-71

[71] Barbagli G, Pellegrini G, Corradini F, Montorsi F, Sansalone S, Butnaru B, et al. One-stage penile urethroplasty using oral mucosa graft and glue. European Urology. 2006;**70**(6):1069-1075

[72] Martins FE, Oliveira T, Oliveira P, Felício J, Dave C, Martins NK. Perineal incision to repair penile urethral strictures is a versatile and cosmetic approach. In: Presented at the 37th Congress of the Societé Internationale d'Urologie; Lisbon, October 19-22. 2017

[73] Martins F, Kulkarni S, Joshi P, Marcelino J, de Oliveira TR, Oliveira P, et al. Kulkarni technique of perineal approach with penile inversion for

surgical repair of anterior urethral strictures: Functional and cosmetic outcomes. The Journal of Urology. 2016;**195**(Suppl. 4):e1001-e1002

[74] Kulkarni S, Barbagli G, Sansalone, Lazzeri M. One-sided anterior urethroplasty: A new dorsal onlay graft technique. BJU International. 2009;**104**(8):1150-1155

[75] Andrich DE, Greenwell TJ, Mundy AR. The problems of penile urethroplasty with particular reference to 2-tage reconstructions. The Journal of Urology. 2003;**170**:87-89

[76] Schreiter F, Noll F. Mesh graft urethroplasty using split thickness graft or foreskin. The Journal of Urology. 1989;**142**(5):1223-1226

[77] Carr LK, MacDiarmid SA, Webster GD. Treatment of complex anterior urethral stricture disease with mesh graft urethroplasty. The Journal of Urology. 1997;**157**(1):104-108

[78] Mori RL, Angermeier KW. Staged urethroplasty in the management of complex anterior urethral stricture disease. Translational Andrology and Urology. 2015;**4**(1):29-34

[79] Sinha RJ, Singh V, Sankhwar SN, Dalela D. Donor site morbidity in oral mucosa graft urethroplasty: Implications of tobacco consumption. BMC Urology. 2009;**9**:15

[80] Vacanti JP, Morse MA, Salzman WM, Domd AJ, Perez-Atayde A, Langer R. Selective cell transplantation using bioabsorbable artificial polymers as matrices. Journal of Pediatric Surgery. 1988;**23**:3-9

[81] Mangera A, Chapple CR. Tissue engineering in urethral reconstruction—An update. Asian Journal Andrology. 2013;**15**:89-92. DOI: 10.1038/aja.2012.91; published online 8 October 2012

[82] Bharadwaj S, Liu G, Shi Y, et al. Multipotent differentiation of human urine-derived stem cells: Potential for therapeutic applications in urology. Stem Cells. 2013;**13**(9):1840-1856

[83] Ikada Y. Challenges in tissue engineering. Journal of the Royal Society Interface. 2006;**3**:589-601

[84] Orabi H, AbouShwareb T, Zang Y, Yoo JJ, Atala A. Cell-seeded tubularized scaffolds for reconstruction of long urethral defects: A preclinical study. European Urology. 2013;**63**(3):531-538

[85] Karatas OF, Cimentepe E, Bayrak O, et al. A new application for urethral strictures: Tacrolimuseluting stent. Journal of Endourology. 2010;**24**(6):1043-1044

[86] Shin JH, Song HY, Chai CG, et al. Tissue hyperplasia: Influence of a paclitaxel-eluting stent—Preliminary study in a canine urethral study. Radiology. 2005;**234**(2):438-444

[87] Spencer J, Blakely S, Daugherty M, Angulo JC, Martins F, Venkatesan K, et al. Clinical and patient-reported outcomes of 1-sided anterior urethroplasty for long-segment or panurethral strictures. Urology. 2018;**111**:208-213

[88] Coursey JW, Morey AF, McAninch JW, et al. Erectile function after anterior urethroplasty. Journal of Urology. 2001;**166**:2273-2276

[89] Erickson BA, Granieri MA, Meeks JJ, McVary KT, Gonzalez CM. Prospective analysis of ejaculatory function after anterior urethral reconstruction. The Journal of Urology. 2010;**184**:238-242

[90] Erickson BA, Granieri MA, Meeks JJ, Cashy JP, Gonzalez CM. Prospective analysis of erectile dysfunction after anterior urethroplasty: Incidence and

**107**

2012

2816 (online)

*Historical Perspective and Innovations in Penile Urethroplasty*

[98] Elliott SP, McAninch JW.

2018

Reconstruction of strictures of penile urethra. In: Smith JA Jr, Howards SS, Preminger GM, Dmochowski RR, editors. Hinman's Atlas of Urologic Surgery. 4th ed. Philadelphia: Elsevier;

[99] McAninch JW. Fasciocutaneous penile flap in reconstruction of

complex anterior urethral strictures. In: McAninch JW, editor. Traumatic and Reconstructive Urology. Philadelphia: W. B. Saunders Company; 1996

*DOI: http://dx.doi.org/10.5772/intechopen.85908*

recovery of function. The Journal of

[91] Patel DP, Elliott SP, Voelzke BB, Erickson BA, McClung CD, Presson AP, et al. Patient reported sexual function after staged penile urethroplasty. Urology. 2015;**86**(2):395-400

[92] Blaschko SD, Sanford MT, Cinman NM, McAninch JW, Breyer BN. De novo erectile dysfunction after anterior urethroplasty: A systematic review and meta-analysis. BJU International.

[93] Granieri M, Webster G, Lentz A, Fraser A, Peterson A. Lower urinary tract symptoms associated with recurrence afterurethroplasstyfor anterior urethral stricture disease. The Journal of Urology. 2014;**191**(4S):e123

[94] Tao H, Jiang YY, Jun Q, Ding X, Jian DL, Jie D, et al. Analysis of risk factors leading to postoperative urethral stricture and bladder neck contracture following transurethral resection of prostate. International Brazilian Journal of Urology. 2016;**42**(2):302-311. DOI: 10.1590/ S1677-5538.IBJU.2014.0500

[95] Campos-Juanatey F, Bugeja S, Ivaz SL, Frost A, Andrich DE, Mundy AR. Management of penile urethral strictures: Challenges and future directions. World Journal of Clinical Urology. 2016;**5**(1):1-10. ISSN: 2219-

[96] Jordan GH, McCammon KA. Surgery of the penis and urethra. In: Wein AJ, editor. Campbell-Walsh Urology. 10th ed. Philadelphia: Elsevier;

[97] Armenakas NA, McAninch JW. Fossa navicularis and meatal stricture

penile flap reconstruction. In: McAninch JW, editor. Traumatic and Reconstructive Urology. Philadelphia: W. B. Saunders Company; 1996

Urology. 2010;**183**:657-661

2013;**112**(5):655-663

*Historical Perspective and Innovations in Penile Urethroplasty DOI: http://dx.doi.org/10.5772/intechopen.85908*

recovery of function. The Journal of Urology. 2010;**183**:657-661

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

[82] Bharadwaj S, Liu G, Shi Y, et al. Multipotent differentiation of human urine-derived stem cells: Potential for therapeutic applications in urology. Stem Cells. 2013;**13**(9):1840-1856

[83] Ikada Y. Challenges in tissue engineering. Journal of the Royal Society Interface. 2006;**3**:589-601

[85] Karatas OF, Cimentepe E, Bayrak O, et al. A new application for urethral strictures: Tacrolimuseluting stent. Journal of Endourology.

2010;**24**(6):1043-1044

2018;**111**:208-213

2001;**166**:2273-2276

2010;**184**:238-242

[84] Orabi H, AbouShwareb T, Zang Y, Yoo JJ, Atala A. Cell-seeded tubularized scaffolds for reconstruction of long urethral defects: A preclinical study. European Urology. 2013;**63**(3):531-538

[86] Shin JH, Song HY, Chai CG, et al. Tissue hyperplasia: Influence of a paclitaxel-eluting stent—Preliminary study in a canine urethral study. Radiology. 2005;**234**(2):438-444

[87] Spencer J, Blakely S, Daugherty M, Angulo JC, Martins F, Venkatesan K, et al. Clinical and patient-reported outcomes of 1-sided anterior urethroplasty for long-segment or panurethral strictures. Urology.

[88] Coursey JW, Morey AF, McAninch JW, et al. Erectile function after anterior urethroplasty. Journal of Urology.

[89] Erickson BA, Granieri MA, Meeks

reconstruction. The Journal of Urology.

[90] Erickson BA, Granieri MA, Meeks JJ, Cashy JP, Gonzalez CM. Prospective analysis of erectile dysfunction after anterior urethroplasty: Incidence and

JJ, McVary KT, Gonzalez CM. Prospective analysis of ejaculatory function after anterior urethral

surgical repair of anterior urethral strictures: Functional and cosmetic outcomes. The Journal of Urology. 2016;**195**(Suppl. 4):e1001-e1002

[74] Kulkarni S, Barbagli G, Sansalone,

Lazzeri M. One-sided anterior urethroplasty: A new dorsal onlay graft technique. BJU International.

[75] Andrich DE, Greenwell TJ, Mundy AR. The problems of penile urethroplasty with particular reference to 2-tage reconstructions. The Journal of

[76] Schreiter F, Noll F. Mesh graft urethroplasty using split thickness graft or foreskin. The Journal of Urology.

[77] Carr LK, MacDiarmid SA, Webster GD. Treatment of complex anterior urethral stricture disease with mesh graft urethroplasty. The Journal of Urology. 1997;**157**(1):104-108

[78] Mori RL, Angermeier KW. Staged urethroplasty in the management of complex anterior urethral stricture disease. Translational Andrology and

[79] Sinha RJ, Singh V, Sankhwar SN, Dalela D. Donor site morbidity in oral mucosa graft urethroplasty: Implications of tobacco consumption.

[80] Vacanti JP, Morse MA, Salzman WM, Domd AJ, Perez-Atayde A, Langer R. Selective cell transplantation using bioabsorbable artificial polymers as matrices. Journal of Pediatric Surgery.

2009;**104**(8):1150-1155

Urology. 2003;**170**:87-89

1989;**142**(5):1223-1226

Urology. 2015;**4**(1):29-34

BMC Urology. 2009;**9**:15

[81] Mangera A, Chapple CR. Tissue engineering in urethral reconstruction—An update. Asian Journal Andrology. 2013;**15**:89-92. DOI: 10.1038/aja.2012.91; published online 8

**106**

1988;**23**:3-9

October 2012

[91] Patel DP, Elliott SP, Voelzke BB, Erickson BA, McClung CD, Presson AP, et al. Patient reported sexual function after staged penile urethroplasty. Urology. 2015;**86**(2):395-400

[92] Blaschko SD, Sanford MT, Cinman NM, McAninch JW, Breyer BN. De novo erectile dysfunction after anterior urethroplasty: A systematic review and meta-analysis. BJU International. 2013;**112**(5):655-663

[93] Granieri M, Webster G, Lentz A, Fraser A, Peterson A. Lower urinary tract symptoms associated with recurrence afterurethroplasstyfor anterior urethral stricture disease. The Journal of Urology. 2014;**191**(4S):e123

[94] Tao H, Jiang YY, Jun Q, Ding X, Jian DL, Jie D, et al. Analysis of risk factors leading to postoperative urethral stricture and bladder neck contracture following transurethral resection of prostate. International Brazilian Journal of Urology. 2016;**42**(2):302-311. DOI: 10.1590/ S1677-5538.IBJU.2014.0500

[95] Campos-Juanatey F, Bugeja S, Ivaz SL, Frost A, Andrich DE, Mundy AR. Management of penile urethral strictures: Challenges and future directions. World Journal of Clinical Urology. 2016;**5**(1):1-10. ISSN: 2219- 2816 (online)

[96] Jordan GH, McCammon KA. Surgery of the penis and urethra. In: Wein AJ, editor. Campbell-Walsh Urology. 10th ed. Philadelphia: Elsevier; 2012

[97] Armenakas NA, McAninch JW. Fossa navicularis and meatal stricture penile flap reconstruction. In: McAninch JW, editor. Traumatic and Reconstructive Urology. Philadelphia: W. B. Saunders Company; 1996

[98] Elliott SP, McAninch JW. Reconstruction of strictures of penile urethra. In: Smith JA Jr, Howards SS, Preminger GM, Dmochowski RR, editors. Hinman's Atlas of Urologic Surgery. 4th ed. Philadelphia: Elsevier; 2018

[99] McAninch JW. Fasciocutaneous penile flap in reconstruction of complex anterior urethral strictures. In: McAninch JW, editor. Traumatic and Reconstructive Urology. Philadelphia: W. B. Saunders Company; 1996

**109**

**Chapter 7**

**Abstract**

**1. Introduction**

**2. Lower urinary tract symptoms**

Dysfunction

*and Achileas Karafotias*

Lower Urinary Tract Symptoms

*Charalampos Konstantinidis, Ioannis Eleftheropoulos* 

(LUTS) and Sexual Function and

In recent years, the coexistence of sexual dysfunction (SD) and lower urinary tract

symptoms (LUTS) has become a popular topic for researchers. Numerous clinical epidemiologic studies have been planned for this reason and have evaluated the relationship between these seemingly irrelevant urological conditions. The connection between SD and LUTS has already been acknowledged, and common pathophysiological pathways have been recognized. In this chapter was attempted to evaluate the impact on patient's quality of life (QoL), common pathophysiological pathways and therapy aspects of this condition. SD and LUTS are common problems among the general population and affect a great percentage of urological patients. It is a subject that affects the community in social, financial, and psychological terms. In this case, research for new treatment options has been triggered as phosphodiesterase type 5 inhibitors established their role as the widely approved combination therapy.

**Keywords:** lower urinary tract symptoms (LUTS), sexual dysfunction (SD), PDE5i

toms has become a popular topic for researchers. Numerous clinical epidemiologic studies have been planned for this reason and have evaluated the relationship between these seemingly irrelevant urological fields of study. In this chapter, an approach to these two fields, their impact on patients' quality of life (QoL), common pathophysiological pathways and therapy aspects are attempted. Both are common problems among the general population and affect a great percentage of urological patients. In this case, research for new treatment options has been triggered as phosphodiesterase type 5 inhibitors established their role as the widely approved combination therapy.

In recent years, the coexistence of sexual dysfunction and lower urinary tract symp-

Lower urinary tract symptoms (LUTS) are a common complaint in adult men and women with a major impact on quality of life (QoL) [1–4]. They can be divided into storage, voiding, and postmicturition symptoms [5]. LUTS are strongly associated with aging [1, 2] and also with a number of modifiable risk factors, suggesting

#### **Chapter 7**

## Lower Urinary Tract Symptoms (LUTS) and Sexual Function and Dysfunction

*Charalampos Konstantinidis, Ioannis Eleftheropoulos and Achileas Karafotias*

#### **Abstract**

In recent years, the coexistence of sexual dysfunction (SD) and lower urinary tract symptoms (LUTS) has become a popular topic for researchers. Numerous clinical epidemiologic studies have been planned for this reason and have evaluated the relationship between these seemingly irrelevant urological conditions. The connection between SD and LUTS has already been acknowledged, and common pathophysiological pathways have been recognized. In this chapter was attempted to evaluate the impact on patient's quality of life (QoL), common pathophysiological pathways and therapy aspects of this condition. SD and LUTS are common problems among the general population and affect a great percentage of urological patients. It is a subject that affects the community in social, financial, and psychological terms. In this case, research for new treatment options has been triggered as phosphodiesterase type 5 inhibitors established their role as the widely approved combination therapy.

**Keywords:** lower urinary tract symptoms (LUTS), sexual dysfunction (SD), PDE5i

#### **1. Introduction**

In recent years, the coexistence of sexual dysfunction and lower urinary tract symptoms has become a popular topic for researchers. Numerous clinical epidemiologic studies have been planned for this reason and have evaluated the relationship between these seemingly irrelevant urological fields of study. In this chapter, an approach to these two fields, their impact on patients' quality of life (QoL), common pathophysiological pathways and therapy aspects are attempted. Both are common problems among the general population and affect a great percentage of urological patients. In this case, research for new treatment options has been triggered as phosphodiesterase type 5 inhibitors established their role as the widely approved combination therapy.

#### **2. Lower urinary tract symptoms**

Lower urinary tract symptoms (LUTS) are a common complaint in adult men and women with a major impact on quality of life (QoL) [1–4]. They can be divided into storage, voiding, and postmicturition symptoms [5]. LUTS are strongly associated with aging [1, 2] and also with a number of modifiable risk factors, suggesting

potential targets for prevention (e.g., metabolic syndrome) [6]. Most elderly men have at least one LUTS [2], which is often mild or not very bothersome [4, 7, 8]. LUTS progression is a dynamic procedure. LUTS may persist and upscale over long time periods, or they may retreat [2]. LUTS have usually been related to bladder outlet obstruction (BOO), which is often caused by an increase of prostatic volume, as a result of benign prostate hyperplasia (BPH) [3, 5]. On the contrary, numerous studies have shown that LUTS are often not related to the BPH [2, 9]. Bladder dysfunction may also cause LUTS, such as detrusor overactivity or overactive bladder syndrome (OAB), detrusor underactivity, and structural or functional abnormalities of the urinary tract and its surrounding tissues [9]. Prostatitis may also cause the appearance of LUTS [10, 11]. Furthermore, there are some nonurological conditions that may be related to urinary symptoms, mainly to nocturia [2].

The definitions of the most common conditions related to LUTS are presented below:


Patient's history must be assessed thoroughly [13–15]. A medical history aims to identify relevant comorbidities and potential causes, including medical and neurological diseases. Lifestyle habits, medication, emotional, and psychological factors must also be reviewed. When relevant, the sexual function should be assessed, preferably with validated symptom questionnaires such as the International Index for Erectile Function (IIEF). The literature recommends, for male LUTS assessment, the use of validated symptom score questionnaire [13, 15]. Several questionnaires have been developed, which are sensitive to symptom changes. In this case, they are helpful in monitoring treatment approaches [16–22]. Symptom scores are helpful in quantifying LUTS and identifying the predominant symptoms. Nevertheless, they are not disease- or age specific.

### **3. Sexual dysfunction**

It is difficult to identify the prevalence of sexual dysfunction in men, because there is no standard definition of sexual dysfunction (SD). Erectile dysfunction

**111**

*Lower Urinary Tract Symptoms (LUTS) and Sexual Function and Dysfunction*

(ED) is defined as the persistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance [23]. Penile erection is a complex phenomenon, which implies coordination among the neurological, vascular, and smooth muscle compartment. It includes arterial dilation, trabecular smooth muscle relaxation, and activation of the corporal veno-occlusive mechanism [24]. ED may affect physical and psychosocial health. It might have a significant impact on the QoL of sufferers and their partners' as well [25–27]. Therefore, ED should not be regarded only as a QoL issue, but also as a potential warning sign of cardiovascular disease (CVD), as it can be an early manifestation of coronary artery and

The pathophysiology of ED may be vasculogenic, neurogenic, anatomical, hormonal, drug-induced, and/or psychogenic [24]. Usually, many pathophysiology pathways can be comorbid and concomitant, negatively impacting on erectile function. In most cases, ED is the result of more than one organic pathophysiological element and, very often, a psychological component. ED was initially classified into three categories based on its etiology. These include organic, psychogenic, and mixed ED. Nowadays, these are recognized as two categories: the psychogenic and the mixed one, as any organic ED has an additional psychogenic impact that interferes with the pathophysiology of ED and causes additional distress to the patient. Epidemiological data have shown a high incidence and prevalence of ED worldwide. The Massachusetts male aging study (MMAS) [25] reported, in noninstitutionalized men aged 40–70 years in the Boston area, an overall prevalence of 52% ED. Prevalence for minimal, moderate, and complete ED was 17.2, 25.2, and 9.6%, respectively. In the Cologne study of men aged 30–80 years, the prevalence of ED was 19.2% [65]. The incidence rate of ED (new cases per 1000 men annually) was 26 in the long-term data from the MMAS study [66] and 19.2 (mean follow-up of

ED shares common risk factors with CVD (e.g., obesity, diabetes mellitus, dyslipidemia, metabolic syndrome, lack of exercise, and smoking) [27, 32–34]. The association among ED and age, diabetes mellitus, body mass index (BMI) [35, 36], obstructive sleep apnea, and hyperhomocysteinemia has been established [37–39]. A number of studies have shown evidence that lifestyle modification [29, 40] and pharmacotherapy [40, 41] for CVD risk factors may also improve sexual function in men with ED. Epidemiological studies have also demonstrated consistent evidence for an association between LUTS and sexual dysfunction, regardless of age, other comorbidities, and behavioral factors [42]. The multinational survey on the aging male (MSAM-7) study (performed in France, Germany, Spain, Italy, the Netherlands, the USA, and the UK) investigated the relationship between LUTS and sexual dysfunction in over 12,000 men aged 50–80 years. From 83% of sexually active men, the prevalence of LUTS was 90%, with the prevalence of ED being 49%. The complete absence of erection was reported in 10% of patients. The prevalence of ejaculatory disorders has been reported in 46% of patients [43]. Association between chronic prostatitis or chronic pelvic pain syndrome (CP/

Surgical interventions to the prostate also have an impact on erectile function according to the type of surgery that was performed [45]. Epidemiologically, there are other risk factors that potentially associate to ED, including psoriasis [46–48], gouty arthritis [49, 50], ankylosing spondylitis [51], nonalcoholic fatty liver [52], chronic liver disorders [53], chronic periodontitis [54], open-angle glaucoma [55], inflammatory bowel disease [56], and complications following transrectal ultrasound (TRUS)

World Health Organization (WHO) and International Classifications of Diseases-10 (ICD-10) define female sexual dysfunction as "the various ways in

*DOI: http://dx.doi.org/10.5772/intechopen.86827*

peripheral vascular disease [28–30].

4.2 years) in a Dutch study [31].

CPPS) and ED is confirmed [44].

guided prostate biopsy [57].

*Lower Urinary Tract Symptoms (LUTS) and Sexual Function and Dysfunction DOI: http://dx.doi.org/10.5772/intechopen.86827*

(ED) is defined as the persistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance [23]. Penile erection is a complex phenomenon, which implies coordination among the neurological, vascular, and smooth muscle compartment. It includes arterial dilation, trabecular smooth muscle relaxation, and activation of the corporal veno-occlusive mechanism [24]. ED may affect physical and psychosocial health. It might have a significant impact on the QoL of sufferers and their partners' as well [25–27]. Therefore, ED should not be regarded only as a QoL issue, but also as a potential warning sign of cardiovascular disease (CVD), as it can be an early manifestation of coronary artery and peripheral vascular disease [28–30].

The pathophysiology of ED may be vasculogenic, neurogenic, anatomical, hormonal, drug-induced, and/or psychogenic [24]. Usually, many pathophysiology pathways can be comorbid and concomitant, negatively impacting on erectile function. In most cases, ED is the result of more than one organic pathophysiological element and, very often, a psychological component. ED was initially classified into three categories based on its etiology. These include organic, psychogenic, and mixed ED. Nowadays, these are recognized as two categories: the psychogenic and the mixed one, as any organic ED has an additional psychogenic impact that interferes with the pathophysiology of ED and causes additional distress to the patient.

Epidemiological data have shown a high incidence and prevalence of ED worldwide. The Massachusetts male aging study (MMAS) [25] reported, in noninstitutionalized men aged 40–70 years in the Boston area, an overall prevalence of 52% ED. Prevalence for minimal, moderate, and complete ED was 17.2, 25.2, and 9.6%, respectively. In the Cologne study of men aged 30–80 years, the prevalence of ED was 19.2% [65]. The incidence rate of ED (new cases per 1000 men annually) was 26 in the long-term data from the MMAS study [66] and 19.2 (mean follow-up of 4.2 years) in a Dutch study [31].

ED shares common risk factors with CVD (e.g., obesity, diabetes mellitus, dyslipidemia, metabolic syndrome, lack of exercise, and smoking) [27, 32–34]. The association among ED and age, diabetes mellitus, body mass index (BMI) [35, 36], obstructive sleep apnea, and hyperhomocysteinemia has been established [37–39]. A number of studies have shown evidence that lifestyle modification [29, 40] and pharmacotherapy [40, 41] for CVD risk factors may also improve sexual function in men with ED. Epidemiological studies have also demonstrated consistent evidence for an association between LUTS and sexual dysfunction, regardless of age, other comorbidities, and behavioral factors [42]. The multinational survey on the aging male (MSAM-7) study (performed in France, Germany, Spain, Italy, the Netherlands, the USA, and the UK) investigated the relationship between LUTS and sexual dysfunction in over 12,000 men aged 50–80 years. From 83% of sexually active men, the prevalence of LUTS was 90%, with the prevalence of ED being 49%. The complete absence of erection was reported in 10% of patients. The prevalence of ejaculatory disorders has been reported in 46% of patients [43]. Association between chronic prostatitis or chronic pelvic pain syndrome (CP/ CPPS) and ED is confirmed [44].

Surgical interventions to the prostate also have an impact on erectile function according to the type of surgery that was performed [45]. Epidemiologically, there are other risk factors that potentially associate to ED, including psoriasis [46–48], gouty arthritis [49, 50], ankylosing spondylitis [51], nonalcoholic fatty liver [52], chronic liver disorders [53], chronic periodontitis [54], open-angle glaucoma [55], inflammatory bowel disease [56], and complications following transrectal ultrasound (TRUS) guided prostate biopsy [57].

World Health Organization (WHO) and International Classifications of Diseases-10 (ICD-10) define female sexual dysfunction as "the various ways in

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

potential targets for prevention (e.g., metabolic syndrome) [6]. Most elderly men have at least one LUTS [2], which is often mild or not very bothersome [4, 7, 8]. LUTS progression is a dynamic procedure. LUTS may persist and upscale over long time periods, or they may retreat [2]. LUTS have usually been related to bladder outlet obstruction (BOO), which is often caused by an increase of prostatic volume, as a result of benign prostate hyperplasia (BPH) [3, 5]. On the contrary, numerous studies have shown that LUTS are often not related to the BPH [2, 9]. Bladder dysfunction may also cause LUTS, such as detrusor overactivity or overactive bladder syndrome (OAB), detrusor underactivity, and structural or functional abnormalities of the urinary tract and its surrounding tissues [9]. Prostatitis may also cause the appearance of LUTS [10, 11]. Furthermore, there are some nonurological conditions that may be related to urinary symptoms, mainly to nocturia [2].

The definitions of the most common conditions related to LUTS are presented

• Acute retention of urine is defined as a painful and palpable bladder when the

• Chronic retention of urine is defined as a nonpainful bladder, which remains palpable even though the patient has urinated. It may also be accompanied by

• Bladder outlet obstruction (BOO) is characterized by reduced urine flow rate and increased detrusor pressure. It can be diagnosed by studying the synchro-

• Benign prostatic obstruction (BPO) is a form of BOO, diagnosed when the

• Detrusor overactivity (DO) is a urodynamic observation characterized by involuntary detrusor contractions during the bladder filling phase [5].

• Overactive bladder (OAB) syndrome is characterized by urinary urgency, with or without urinary incontinence, usually with increased daytime frequency and nocturia, and in this case, there is no proven infection or other obvious pathology [12].

Patient's history must be assessed thoroughly [13–15]. A medical history aims to identify relevant comorbidities and potential causes, including medical and neurological diseases. Lifestyle habits, medication, emotional, and psychological factors must also be reviewed. When relevant, the sexual function should be assessed, preferably with validated symptom questionnaires such as the International Index for Erectile Function (IIEF). The literature recommends, for male LUTS assessment, the use of validated symptom score questionnaire [13, 15]. Several questionnaires have been developed, which are sensitive to symptom changes. In this case, they are helpful in monitoring treatment approaches [16–22]. Symptom scores are helpful in quantifying LUTS and identifying the predominant symptoms. Nevertheless, they

It is difficult to identify the prevalence of sexual dysfunction in men, because there is no standard definition of sexual dysfunction (SD). Erectile dysfunction

nous values of detrusor pressure and urine flow rate [5].

cause of outlet obstruction is known to be BPH [5].

**110**

below:

patient cannot urinate [5].

incontinence [5].

are not disease- or age specific.

**3. Sexual dysfunction**

which an individual is unable to participate in a sexual relationship as she would wish" [58]. There are three categories of sexual dysfunction: female sexual interestarousal disorder, female orgasmic disorder, and genito-pelvic pain-penetration disorder [59]. It is estimated that 10% of women suffer from female sexual interestarousal disorder and 3.5–35% present orgasmic problems [60].

Validated psychometric questionnaires, such as the International Index for Erectile Function (IIEF) [61] or the sexual health inventory for men (SHIM) [62], are the assessment tools needed in different sexual function domains (i.e., erectile function, sexual desire, intercourse, orgasmic function, and overall satisfaction), as well as for the potential impact of a specific treatment modality. The use of the erectile hardness score for the assessment of penile rigidity in practice and in clinical trial research is supported by psychometric analyses [63]. Patients should be screened for symptoms of possible hypogonadism (testosterone deficiency), libido, fatigue, cognitive impairment, and LUTS. Even though LUTS does not represent a contraindication to treat a patient for late-onset hypogonadism, screening for LUTS severity is clinically relevant [64].

#### **4. The relationship between ED and LUTS**

A lot of epidemiological studies demonstrate the coexistence of ED and LUTS. It is also proven that the existence of LUTS is a risk factor for ED. The patient's age and the severity of LUTS are independent prognostic factors for ED, as well. Although it is not clear if LUTS lead to ED, or ED results to LUTS, or these conditions are just coexisting, their relation is very narrow and clear, especially in older patients. Therefore, men who suffer from LUTS should be checked for ED and men who present ED should be evaluated for LUTS. There are four theories that try to correlate LUTS with ED. These theories include deregulation of NO/NOS system, increased sympathetic tone (autonomic hyperactivity (AH)), up-regulation of Rho-kinase, and chronic hypoxia. Common vascular risk factors can combine and support these theories.

#### **4.1 Alteration in nitric oxide (NO)**

The role of nitric oxide (NO) in erectile function is well known as the main regulator of penile corporal smooth muscle relaxation and resultant erection. The decrease in NO/cyclic guanosine monophosphate (cGMP) has the effect of reduction in NO synthase (NOS) due to endothelial dysfunction. Luck or reduction of smooth muscle relaxation of the bladder neck, prostate and urethra may lead to LUTS. The NO system has been shown to be down-regulated in the transition zone of the prostate in BPH when compared with normal controls [67, 68].

#### **4.2 Autonomic hyperactivity (AH)**

AH, as a component of the metabolic syndrome, refers to dysregulation of sympathetic and parasympathetic tone. Increased sympathetic tone results in flaccidity and antagonizes penile erection, due to vasoconstriction. Parasympathetic activation can lead to prostate smooth muscle contraction (due to activation of the M2 receptors), so nonrelaxing bladder neck, prostatic urethra, and pelvic floor may lead to LUTS [67, 68].

#### **4.3 RhoA/rho-kinase-calcium-sensitizing pathway**

Smooth muscle tone is adjusted commonly not only through the calciumdependent mechanism, but also through the activity of RhoA/ROCK calcium

**113**

*Lower Urinary Tract Symptoms (LUTS) and Sexual Function and Dysfunction*

pathway. Activation of RhoA-ROCK pathway can affect smooth muscle relaxation and finally increase ED and LUTS. Therefore, penile RhoA/ROCK signaling was increased in pathologic situations associated with ED, like diabetes and involuntary bladder contractions were associated with increased signaling of the muscarinic receptor-activated RhoA/ROCK pathway. Increase in RhoA/ROCK was demonstrated in corpora cavernosa and bladder of spontaneously hypertensive rats (SHR), a rat strain genetically prone to develop BPH and OAB. The inhibition of ROCK reduces bladder hyperactivity, limits contractions in bladder strips from

Atherosclerosis of the bladder, prostate, and penis serves an extra assumption linking LUTS with ED. The theory claims that the risks for ED (smoking, hypertension, hypercholesterolemia, and diabetes mellitus) also affect on LUTS. An epidemiologic study was published that supports this theory, all men and women who had two risk factors of atherosclerosis (diabetes mellitus, hypertension, hyperlipidemia, and nicotine use) and had a statistically higher International Prostate Symptom Score (IPSS) compared with those with one or no risk factors at all. Smooth muscle changes in the prostate, bladder, and penis of animal models of hypercholesterolemia and pelvic ischemia are quite similar. Hypoxia drives to overexpression of TGFb1, and converted prostanoid production has been suggested as potential mechanisms. Similarly, penile ischemia leads to smooth muscle loss in it and ends up with ED. Likewise, the loss of smooth muscle in the bladder may decrease compliance and increase the symptoms of LUTS. Additionally, bladder ischemia either from BOO or pelvic vascular disease would result in bladder smooth muscle loss with the resultant replacement of collagen deposition and fibrosis as well as loss of compliance, overactivity, and impaired contractility. Loss of smooth muscle in the prostate can induce a less distensible urethra, a decreased urinary flow rate, increased flow resistance, and worsening LUTS. Pelvic atherosclerosis associated with the previously described theories, as pelvic ischemia/atherosclerosis is a component of the metabolic syndrome/AH, up-regulates Rk activity, and reduces

*DOI: http://dx.doi.org/10.5772/intechopen.86827*

SHR, and improves erectile function [67, 68].

**4.4 Pelvic atherosclerosis**

NOS expression. [35, 67, 68].

**5. Multifactorial interaction between LUTS and ED**

work productivity, and decreased enjoyment of sexual activity [35, 69].

attributed to educational status, rather than economic status [69].

It is well known that sexual life, behavior, and relationships are very important for a good and healthy life, and they are affected by attitudes, social models and overall health. For sexual health many aspects are necessary and not only the absence of infirmity, disease or dysfunction. Sexual practice and habits have changed a lot over the last years, it is over also known that the sexual frequency and different practices are reducing with age. On the other hand, some sexual behaviors are more common in our days, like anal sex. These changes are more likely to be

LUTS are significant indicators of a disease when the patient, caregiver, or partner realizes it, and change of them may lead him/her to find help from professionals. It is also known (from the 6th International Consultation on Incontinence 2016) that from overall world's population, 46% (of the adults >20 years) experience LUTS, 11.8% suffer from OAB symptoms, 8% complain of some type of urinary incontinence (UI), and 4% of severe stress urinary incontinence (SUI). Urinary incontinence is associated with reduced QoL, higher rates of depression, reduced

*Lower Urinary Tract Symptoms (LUTS) and Sexual Function and Dysfunction DOI: http://dx.doi.org/10.5772/intechopen.86827*

pathway. Activation of RhoA-ROCK pathway can affect smooth muscle relaxation and finally increase ED and LUTS. Therefore, penile RhoA/ROCK signaling was increased in pathologic situations associated with ED, like diabetes and involuntary bladder contractions were associated with increased signaling of the muscarinic receptor-activated RhoA/ROCK pathway. Increase in RhoA/ROCK was demonstrated in corpora cavernosa and bladder of spontaneously hypertensive rats (SHR), a rat strain genetically prone to develop BPH and OAB. The inhibition of ROCK reduces bladder hyperactivity, limits contractions in bladder strips from SHR, and improves erectile function [67, 68].

#### **4.4 Pelvic atherosclerosis**

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

arousal disorder and 3.5–35% present orgasmic problems [60].

**4. The relationship between ED and LUTS**

**4.1 Alteration in nitric oxide (NO)**

**4.2 Autonomic hyperactivity (AH)**

**4.3 RhoA/rho-kinase-calcium-sensitizing pathway**

lead to LUTS [67, 68].

which an individual is unable to participate in a sexual relationship as she would wish" [58]. There are three categories of sexual dysfunction: female sexual interestarousal disorder, female orgasmic disorder, and genito-pelvic pain-penetration disorder [59]. It is estimated that 10% of women suffer from female sexual interest-

Function (IIEF) [61] or the sexual health inventory for men (SHIM) [62], are the assessment tools needed in different sexual function domains (i.e., erectile function, sexual desire, intercourse, orgasmic function, and overall satisfaction), as well as for the potential impact of a specific treatment modality. The use of the erectile hardness score for the assessment of penile rigidity in practice and in clinical trial research is supported by psychometric analyses [63]. Patients should be screened for symptoms of possible hypogonadism (testosterone deficiency), libido, fatigue, cognitive impairment, and LUTS. Even though LUTS does not represent a contraindication to treat a patient for late-onset hypogonadism, screening for LUTS severity is clinically relevant [64].

Validated psychometric questionnaires, such as the International Index for Erectile

A lot of epidemiological studies demonstrate the coexistence of ED and LUTS. It is also proven that the existence of LUTS is a risk factor for ED. The patient's age and the severity of LUTS are independent prognostic factors for ED, as well. Although it is not clear if LUTS lead to ED, or ED results to LUTS, or these conditions are just coexisting, their relation is very narrow and clear, especially in older patients. Therefore, men who suffer from LUTS should be checked for ED and men who present ED should be evaluated for LUTS. There are four theories that try to correlate LUTS with ED. These theories include deregulation of NO/NOS system, increased sympathetic tone (autonomic hyperactivity (AH)), up-regulation of Rho-kinase, and chronic hypoxia. Common vascular risk factors can combine and support these theories.

The role of nitric oxide (NO) in erectile function is well known as the main regulator of penile corporal smooth muscle relaxation and resultant erection. The decrease in NO/cyclic guanosine monophosphate (cGMP) has the effect of reduction in NO synthase (NOS) due to endothelial dysfunction. Luck or reduction of smooth muscle relaxation of the bladder neck, prostate and urethra may lead to LUTS. The NO system has been shown to be down-regulated in the transition zone

AH, as a component of the metabolic syndrome, refers to dysregulation of sympathetic and parasympathetic tone. Increased sympathetic tone results in flaccidity and antagonizes penile erection, due to vasoconstriction. Parasympathetic activation can lead to prostate smooth muscle contraction (due to activation of the M2 receptors), so nonrelaxing bladder neck, prostatic urethra, and pelvic floor may

Smooth muscle tone is adjusted commonly not only through the calciumdependent mechanism, but also through the activity of RhoA/ROCK calcium

of the prostate in BPH when compared with normal controls [67, 68].

**112**

Atherosclerosis of the bladder, prostate, and penis serves an extra assumption linking LUTS with ED. The theory claims that the risks for ED (smoking, hypertension, hypercholesterolemia, and diabetes mellitus) also affect on LUTS. An epidemiologic study was published that supports this theory, all men and women who had two risk factors of atherosclerosis (diabetes mellitus, hypertension, hyperlipidemia, and nicotine use) and had a statistically higher International Prostate Symptom Score (IPSS) compared with those with one or no risk factors at all. Smooth muscle changes in the prostate, bladder, and penis of animal models of hypercholesterolemia and pelvic ischemia are quite similar. Hypoxia drives to overexpression of TGFb1, and converted prostanoid production has been suggested as potential mechanisms. Similarly, penile ischemia leads to smooth muscle loss in it and ends up with ED. Likewise, the loss of smooth muscle in the bladder may decrease compliance and increase the symptoms of LUTS. Additionally, bladder ischemia either from BOO or pelvic vascular disease would result in bladder smooth muscle loss with the resultant replacement of collagen deposition and fibrosis as well as loss of compliance, overactivity, and impaired contractility. Loss of smooth muscle in the prostate can induce a less distensible urethra, a decreased urinary flow rate, increased flow resistance, and worsening LUTS. Pelvic atherosclerosis associated with the previously described theories, as pelvic ischemia/atherosclerosis is a component of the metabolic syndrome/AH, up-regulates Rk activity, and reduces NOS expression. [35, 67, 68].

#### **5. Multifactorial interaction between LUTS and ED**

LUTS are significant indicators of a disease when the patient, caregiver, or partner realizes it, and change of them may lead him/her to find help from professionals. It is also known (from the 6th International Consultation on Incontinence 2016) that from overall world's population, 46% (of the adults >20 years) experience LUTS, 11.8% suffer from OAB symptoms, 8% complain of some type of urinary incontinence (UI), and 4% of severe stress urinary incontinence (SUI). Urinary incontinence is associated with reduced QoL, higher rates of depression, reduced work productivity, and decreased enjoyment of sexual activity [35, 69].

It is well known that sexual life, behavior, and relationships are very important for a good and healthy life, and they are affected by attitudes, social models and overall health. For sexual health many aspects are necessary and not only the absence of infirmity, disease or dysfunction. Sexual practice and habits have changed a lot over the last years, it is over also known that the sexual frequency and different practices are reducing with age. On the other hand, some sexual behaviors are more common in our days, like anal sex. These changes are more likely to be attributed to educational status, rather than economic status [69].

From a physiological prospect, the functions of pelvic organ functions are related as there is a direct relationship with the neuronal network of the pelvis that includes bladder, bowel, and sexual functions. Furthermore, vascular, hormonal, cellular, and other factors comprehensively affect pelvic organ functions. LUTS and ED in males share common pathophysiological pathways [4].

#### **6. Effects of LUTS/incontinence on male sexual function: epidemiological data**

Many large studies over the last years have proved the coexistence of SD in men with storage and voiding LUTS. Statistics from the Health Improvement Network database showed that from 11,327 men in the UK, there was a rise in the overall prevalence of recorded SD from 1.7% in 2000 to 4.9% in 2007. The odds ratio (OR) for ED was 3.0 (2.6–3.4) for storage LUTS, 2.6 (2.4–2.7) for voiding LUTS, and 4.0 (3.4–4.8) for voiding and storage LUTS. The EpiLUTS study (a cross-sectional, population-representative survey in the UK, Sweden, and the USA with 6326 men) show off an impact of OAB on sexual health. Both OAB wet and OAB dry were associated with poor sexual health, diminished enjoyment of sex (P < 0.0001), and decreased sexual activity. OAB dry/wet was very significant predictors of ED and ejaculatory dysfunction (EjD) in men. According to a study by Rosen et al., the attendance and severity of LUTS are independent risk factors for SD in older men [69].

LUTS are common in older men. While LUTS have a multifactorial etiology, BOO/BPH has traditionally been considered as one of the most common causes of LUTS. These symptoms, which include dribbling and urgency with leaking, nocturia, and difficulty in urinating, can also impact the sexual function, probably due to impact on QoL [70].

#### **7. Medical and surgical therapy for LUTS and its impact on sexual function**

The efficacy of all currently available treatments for LUTS is well studied. However, the negative impact of them on erectile function is under evaluation. Behavior modification therapies and phytotherapies seem to have minimal or no impact on sexual function, and even less efficacy on LUTS treatment. On the other hand, α-blockers, 5α-reductase inhibitors, and prostatic surgery are associated with improvement in LUTS, but they usually have a negative impact on the sexual function [68]. Many clinical trials have reported on the efficacy of chronic treatment with phosphodiesterase type 5 inhibitors (PDE5-Is), either alone or in combination with other therapies, in treating LUTS in men with or without ED [71].

α-Blockers such as alfuzosin, doxazosin, tamsulosin, and silodosin have shown similar efficacy, but their effect on sexual function is variable. They seem to have a slightly positive impact on erectile function. However, they can have a negative impact on orgasmic function and ejaculation [72]. Originally, the abnormal ejaculate was thought to be retrograde. However, it seems likely to be due to a decrease or absence of seminal fluid, possibly by a central effect. α-Blockers decrease the prostate secretion and inhibit the contraction of seminal vesicles as both effects are mediated by the sympathetic adrenergic system.

5α-Reductase inhibitors (5-ARIs) are usually offered to men with LUTS who have a prostate estimated to be larger than 40 ml and who are considered to be at high risk of progression [73–75]. Compared to α-blockers, 5-ARIs have a greater

**115**

function [92].

*Lower Urinary Tract Symptoms (LUTS) and Sexual Function and Dysfunction*

impact on sexual function. The side effects most frequently notified are reduced libido, ED, and ejaculation disorders such as dry orgasm, ejaculation failure, or decreased semen volume [76–78]. It must be mentioned that the effect of 5-ARIs on

Regarding surgical options, transurethral resection of the prostate (TURP) and transurethral incision of the prostate (TUIP) are the gold standard surgical techniques for BPH/BOO treatment. Dry orgasm after these operations ranges from 30.4 to 96.9% and 6.1 to 55.1%, respectively. Heterogeneous data are reported, mainly because only a few studies analyzed these rates [79–81] in a prospective fashion. ED has been found ranging from 3.4 to 32.4% [80, 81] after TURP.

Laser procedures, such as GreenLight photoselective vaporization of the prostate (PVP) and holmium laser enucleation of the prostate (HoLEP) are widely offered for BOO/BPH as well. The impact of GreenLight on sexual function seems to be close to that of TURP. One single study, comparing these two prostatic surgery techniques, reported no significant difference in the rate of retrograde ejaculation [82]. There is also no difference reported between TURP and PVP for erectile function [83, 84]. HoLEP seems to have comparable results. Specifically, the incidence of retrograde ejaculation and erectile dysfunction is comparable between HoLEP and TURP [85, 86]. It is reported that almost 75% of sexually active patients have retrograde ejaculation after HoLEP. Currently, both GreenLight and HoLEP surgeons are

Transurethral thermotherapy and microwave techniques such as transurethral needle ablation (TUNA) seem to have lower rates of retrograde ejaculation comparing to TURP. A few studies report that the incidence of retrograde ejaculation seems to be much lower compared to TURP, with no reported cases in the TUNA cohort, compared to the 45% of the TURP arm [89–91]. Urolift/prostatic urethral lift (PUL) is an alternative option and has shown positive results in terms of sexual

Currently, because of the increase in life expectancy, patients with LUTS often wish to preserve or to improve their sexual function according to their treatments. Physicians may focus on the symptoms without considering patients' wishes and expectations. In those cases, despite successful treatment, many patients still complain about their QoL due to the procedure or medication side effects.

Phosphodiesterase type 5 (PDE5) is expressed in the whole of the lower urinary tract, including the urethra, prostate, and bladder. All these organs are targets of PDE5-Is [93–96]. PDE5 is prominently localized in the stroma and in the vascular bed (endothelial and smooth muscle cells), suggesting the action of PDE5-I on

McVary et al. [97], in 2007, evaluated the safety and efficacy of tadalafil for the treatment of LUTS in men with or without ED, for the first time. A total of 479 patients were screened. After a 4-week washout and 4-week placebo run-in period, 281 were randomly assigned to a 6-week treatment with once-daily placebo or tadalafil 5 mg. After 6 weeks, the remaining 261 patients were assigned to continue with placebo for another 6 weeks (a total of 12 weeks of once-daily placebo treatment) or to dose escalate tadalafil to 20 mg once daily. Of 143 placebo-assigned patients, 121 (84.6%) were sexually active, 84 (59.2%) had no erectile dysfunction, and 76 (53.1%) were sexually active despite ED. On the other hand, 138 men treated with 5 or 20 mg tadalafil, 107 (77.5%) were sexually active, 99 (71.7%) had normal sexual function, and 80 (58.0%) were sexually active despite ED. The IPSS

*DOI: http://dx.doi.org/10.5772/intechopen.86827*

ejaculatory function is currently poorly studied.

trying to develop ejaculation preserving techniques [87, 88].

**8. Medical therapy for ED and its impact on LUTS**

smooth muscle contraction and blood flow.

#### *Lower Urinary Tract Symptoms (LUTS) and Sexual Function and Dysfunction DOI: http://dx.doi.org/10.5772/intechopen.86827*

impact on sexual function. The side effects most frequently notified are reduced libido, ED, and ejaculation disorders such as dry orgasm, ejaculation failure, or decreased semen volume [76–78]. It must be mentioned that the effect of 5-ARIs on ejaculatory function is currently poorly studied.

Regarding surgical options, transurethral resection of the prostate (TURP) and transurethral incision of the prostate (TUIP) are the gold standard surgical techniques for BPH/BOO treatment. Dry orgasm after these operations ranges from 30.4 to 96.9% and 6.1 to 55.1%, respectively. Heterogeneous data are reported, mainly because only a few studies analyzed these rates [79–81] in a prospective fashion. ED has been found ranging from 3.4 to 32.4% [80, 81] after TURP.

Laser procedures, such as GreenLight photoselective vaporization of the prostate (PVP) and holmium laser enucleation of the prostate (HoLEP) are widely offered for BOO/BPH as well. The impact of GreenLight on sexual function seems to be close to that of TURP. One single study, comparing these two prostatic surgery techniques, reported no significant difference in the rate of retrograde ejaculation [82]. There is also no difference reported between TURP and PVP for erectile function [83, 84]. HoLEP seems to have comparable results. Specifically, the incidence of retrograde ejaculation and erectile dysfunction is comparable between HoLEP and TURP [85, 86]. It is reported that almost 75% of sexually active patients have retrograde ejaculation after HoLEP. Currently, both GreenLight and HoLEP surgeons are trying to develop ejaculation preserving techniques [87, 88].

Transurethral thermotherapy and microwave techniques such as transurethral needle ablation (TUNA) seem to have lower rates of retrograde ejaculation comparing to TURP. A few studies report that the incidence of retrograde ejaculation seems to be much lower compared to TURP, with no reported cases in the TUNA cohort, compared to the 45% of the TURP arm [89–91]. Urolift/prostatic urethral lift (PUL) is an alternative option and has shown positive results in terms of sexual function [92].

Currently, because of the increase in life expectancy, patients with LUTS often wish to preserve or to improve their sexual function according to their treatments. Physicians may focus on the symptoms without considering patients' wishes and expectations. In those cases, despite successful treatment, many patients still complain about their QoL due to the procedure or medication side effects.

#### **8. Medical therapy for ED and its impact on LUTS**

Phosphodiesterase type 5 (PDE5) is expressed in the whole of the lower urinary tract, including the urethra, prostate, and bladder. All these organs are targets of PDE5-Is [93–96]. PDE5 is prominently localized in the stroma and in the vascular bed (endothelial and smooth muscle cells), suggesting the action of PDE5-I on smooth muscle contraction and blood flow.

McVary et al. [97], in 2007, evaluated the safety and efficacy of tadalafil for the treatment of LUTS in men with or without ED, for the first time. A total of 479 patients were screened. After a 4-week washout and 4-week placebo run-in period, 281 were randomly assigned to a 6-week treatment with once-daily placebo or tadalafil 5 mg. After 6 weeks, the remaining 261 patients were assigned to continue with placebo for another 6 weeks (a total of 12 weeks of once-daily placebo treatment) or to dose escalate tadalafil to 20 mg once daily. Of 143 placebo-assigned patients, 121 (84.6%) were sexually active, 84 (59.2%) had no erectile dysfunction, and 76 (53.1%) were sexually active despite ED. On the other hand, 138 men treated with 5 or 20 mg tadalafil, 107 (77.5%) were sexually active, 99 (71.7%) had normal sexual function, and 80 (58.0%) were sexually active despite ED. The IPSS

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

ED in males share common pathophysiological pathways [4].

**epidemiological data**

men [69].

impact on QoL [70].

**function**

**6. Effects of LUTS/incontinence on male sexual function:** 

From a physiological prospect, the functions of pelvic organ functions are related as there is a direct relationship with the neuronal network of the pelvis that includes bladder, bowel, and sexual functions. Furthermore, vascular, hormonal, cellular, and other factors comprehensively affect pelvic organ functions. LUTS and

Many large studies over the last years have proved the coexistence of SD in men with storage and voiding LUTS. Statistics from the Health Improvement Network database showed that from 11,327 men in the UK, there was a rise in the overall prevalence of recorded SD from 1.7% in 2000 to 4.9% in 2007. The odds ratio (OR) for ED was 3.0 (2.6–3.4) for storage LUTS, 2.6 (2.4–2.7) for voiding LUTS, and 4.0 (3.4–4.8) for voiding and storage LUTS. The EpiLUTS study (a cross-sectional, population-representative survey in the UK, Sweden, and the USA with 6326 men) show off an impact of OAB on sexual health. Both OAB wet and OAB dry were associated with poor sexual health, diminished enjoyment of sex (P < 0.0001), and decreased sexual activity. OAB dry/wet was very significant predictors of ED and ejaculatory dysfunction (EjD) in men. According to a study by Rosen et al., the attendance and severity of LUTS are independent risk factors for SD in older

LUTS are common in older men. While LUTS have a multifactorial etiology, BOO/BPH has traditionally been considered as one of the most common causes of LUTS. These symptoms, which include dribbling and urgency with leaking, nocturia, and difficulty in urinating, can also impact the sexual function, probably due to

**7. Medical and surgical therapy for LUTS and its impact on sexual** 

with other therapies, in treating LUTS in men with or without ED [71].

mediated by the sympathetic adrenergic system.

The efficacy of all currently available treatments for LUTS is well studied. However, the negative impact of them on erectile function is under evaluation. Behavior modification therapies and phytotherapies seem to have minimal or no impact on sexual function, and even less efficacy on LUTS treatment. On the other hand, α-blockers, 5α-reductase inhibitors, and prostatic surgery are associated with improvement in LUTS, but they usually have a negative impact on the sexual function [68]. Many clinical trials have reported on the efficacy of chronic treatment with phosphodiesterase type 5 inhibitors (PDE5-Is), either alone or in combination

α-Blockers such as alfuzosin, doxazosin, tamsulosin, and silodosin have shown similar efficacy, but their effect on sexual function is variable. They seem to have a slightly positive impact on erectile function. However, they can have a negative impact on orgasmic function and ejaculation [72]. Originally, the abnormal ejaculate was thought to be retrograde. However, it seems likely to be due to a decrease or absence of seminal fluid, possibly by a central effect. α-Blockers decrease the prostate secretion and inhibit the contraction of seminal vesicles as both effects are

5α-Reductase inhibitors (5-ARIs) are usually offered to men with LUTS who have a prostate estimated to be larger than 40 ml and who are considered to be at high risk of progression [73–75]. Compared to α-blockers, 5-ARIs have a greater

**114**

(including the IPSS-QoL question) and BII questionnaires were used in order to evaluate LUTS. Maximum urinary flow rate (Qmax) and average urinary flow rate (Qave) of free uroflowmetry were record and post-void residual urine (PVR) was measured by ultrasound after uroflowmetry. The erectile function (EF) domain of the International Index of Erectile Function (IIEF) questionnaire (questions 1–5 and 15) was used to estimate the sexual function.

Since 2007, numerous studies proved the safety and efficacy of PDE5s as a medical therapy for both LUTS and ED. Bora Irer et al. [98] studied LUTS, nocturia, SD, and the status of QoL in men with obstructive sleep apnea syndrome (OSAS). Patients applied continuous positive airway pressure (CPAP) treatment, which is one of the most effective treatments for OSAS, supplying positive air pressure for the opening of the respiratory tract and keeping high saturation of oxygen. Changes in IPSS, IIEF, Overactive Bladder Syndrome Score (OABSS), International Consultation on Incontinence Questionnaire for Male LUTS (ICIQ-MLUTS), Neuro-quality of life score (Nqol), 36-item Short Form Health Survey (SF-36), and Benign Prostatic Hyperplasia Impact Index (BII); the frequency of nocturia; and night-time urine volume were reported. After CPAP treatment, significant changes and improvements on these symptoms and QoL were observed. It has been shown that the frequency of nocturia decreases and erectile function and QoL improves in patients with OSAS under CPAP treatment [99, 100].

#### **9. Conclusion**

SD and LUTS are confirmed to have a strong connection. It is implied by common pathophysiological paths that seem to link these two complications, which have a great impact on a significant percentage of urological patients. For men, PDE5s inhibitors are the milestone of medical treatment for ED and LUTS. Their safety and efficacy are widely accepted. More studies need to support this relatively new field of research for both LUTS and SD, and new treatments may be used as an alternative in near future.

#### **Author details**

Charalampos Konstantinidis1,2\*, Ioannis Eleftheropoulos2 and Achileas Karafotias2

1 Urology and Neuro-Urology Unit, National Rehabilitation Center, Athens, Greece

2 Urology Department, General Hospital "Asklepieio Voulas", Athens, Greece

\*Address all correspondence to: konstantinidischaralampos@yahoo.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**117**

*Lower Urinary Tract Symptoms (LUTS) and Sexual Function and Dysfunction*

[8] Ficarra V et al. The role of inflammation in lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and its potential impact on medical therapy. Current Urology Reports. 2014;**15**:463 https://www.ncbi.nlm.nih.gov/

[9] He Q et al. Metabolic syndrome, inflammation and lower urinary tract symptoms: Possible translational links. Prostate Cancer and Prostatic Diseases. 2016;**19**:7 https://www.ncbi.nlm.nih.

[10] Drake MJ. Do we need a new definition of the overactive bladder syndrome? ICI-RS 2013. Neurourology

and Urodynamics. 2014;**33**:622 http://www.ncbi.nlm.nih.gov/

[11] Novara G et al. Critical review of guidelines for BPH diagnosis and treatment strategy. European Urology Supplements. 2006;**4**:418 http:// eu-acme.org/europeanurology/upload\_

[12] McVary KT et al. Update on AUA guideline on the management of benign prostatic hyperplasia. The Journal of Urology. 2011;**185**:1793 https://www. ncbi.nlm.nih.gov/pubmed/21420124

[13] Bosch J et al. Etiology, patient assessment and predicting outcome

Consultation on Urological Diseases Male LUTS Guideline. 2013;**2013**:37

[14] Martin RM et al. Lower urinary tract symptoms and risk of prostate cancer: The HUNT 2 cohort, Norway. International Journal of Cancer. 2008;**123**:1924 https://www.ncbi.nlm.

[15] Young JM et al. Are men with lower urinary tract symptoms at increased risk

from therapy. International

nih.gov/pubmed/18661522

pubmed/25312251

gov/pubmed/26391088

pubmed/24838519

articles/Novara2.pdf

*DOI: http://dx.doi.org/10.5772/intechopen.86827*

[1] Kupelian V et al. Prevalence of lower urinary tract symptoms and effect on quality of life in a racially and ethnically diverse random sample: The Boston area community health (BACH) survey. Archives of Internal Medicine. 2006;**166**:2381 https://www.ncbi.nlm.

**References**

nih.gov/pubmed/17130393

gov/pubmed/24486308

[2] Agarwal A et al. What is the most bothersome lower urinary tract symptom? Individual- and population-level perspectives for both men and women. European Urology. 2014;**65**:1211 https://www.ncbi.nlm.nih.

[3] De Ridder D et al. Urgency and other lower urinary tract symptoms in men aged >/= 40 years: A Belgian epidemiological survey using the ICIQ-MLUTS questionnaire. International Journal of Clinical Practice. 2015;**69**:358

https://www.ncbi.nlm.nih.gov/

[4] Taub DA et al. The economics of benign prostatic hyperplasia and lower urinary tract symptoms in the United States. Current Urology Reports. 2006;**7**:272 https://www.ncbi.nlm.nih.

pubmed/25648652

gov/pubmed/16930498

gov/pubmed/18423969

pubmed/24602293

[5] Chapple C, Abrams P. Lower Urinary Tract Symptoms (LUTS): An International Consultation On Male LUTS. Societe Internationale d'Urologie

(SIU). ISBN: 978-0-9877465-4-2

[6] Chapple CR et al. Lower urinary tract symptoms revisited: A broader clinical perspective. European Urology. 2008;**54**:563 https://www.ncbi.nlm.nih.

[7] Gacci M et al. Metabolic syndrome and benign prostatic enlargement: A systematic review and meta-analysis. BJU International. 2015;**115**:24 https://www.ncbi.nlm.nih.gov/

*Lower Urinary Tract Symptoms (LUTS) and Sexual Function and Dysfunction DOI: http://dx.doi.org/10.5772/intechopen.86827*

#### **References**

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

and 15) was used to estimate the sexual function.

patients with OSAS under CPAP treatment [99, 100].

Charalampos Konstantinidis1,2\*, Ioannis Eleftheropoulos2

provided the original work is properly cited.

**9. Conclusion**

alternative in near future.

**Author details**

(including the IPSS-QoL question) and BII questionnaires were used in order to evaluate LUTS. Maximum urinary flow rate (Qmax) and average urinary flow rate (Qave) of free uroflowmetry were record and post-void residual urine (PVR) was measured by ultrasound after uroflowmetry. The erectile function (EF) domain of the International Index of Erectile Function (IIEF) questionnaire (questions 1–5

Since 2007, numerous studies proved the safety and efficacy of PDE5s as a medical therapy for both LUTS and ED. Bora Irer et al. [98] studied LUTS, nocturia, SD, and the status of QoL in men with obstructive sleep apnea syndrome (OSAS). Patients applied continuous positive airway pressure (CPAP) treatment, which is one of the most effective treatments for OSAS, supplying positive air pressure for the opening of the respiratory tract and keeping high saturation of oxygen. Changes in IPSS, IIEF, Overactive Bladder Syndrome Score (OABSS), International Consultation on Incontinence Questionnaire for Male LUTS (ICIQ-MLUTS), Neuro-quality of life score (Nqol), 36-item Short Form Health Survey (SF-36), and Benign Prostatic Hyperplasia Impact Index (BII); the frequency of nocturia; and night-time urine volume were reported. After CPAP treatment, significant changes and improvements on these symptoms and QoL were observed. It has been shown that the frequency of nocturia decreases and erectile function and QoL improves in

SD and LUTS are confirmed to have a strong connection. It is implied by common pathophysiological paths that seem to link these two complications, which have a great impact on a significant percentage of urological patients. For men, PDE5s inhibitors are the milestone of medical treatment for ED and LUTS. Their safety and efficacy are widely accepted. More studies need to support this relatively new field of research for both LUTS and SD, and new treatments may be used as an

1 Urology and Neuro-Urology Unit, National Rehabilitation Center, Athens, Greece

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

2 Urology Department, General Hospital "Asklepieio Voulas", Athens, Greece

\*Address all correspondence to: konstantinidischaralampos@yahoo.com

and Achileas Karafotias2

**116**

[1] Kupelian V et al. Prevalence of lower urinary tract symptoms and effect on quality of life in a racially and ethnically diverse random sample: The Boston area community health (BACH) survey. Archives of Internal Medicine. 2006;**166**:2381 https://www.ncbi.nlm. nih.gov/pubmed/17130393

[2] Agarwal A et al. What is the most bothersome lower urinary tract symptom? Individual- and population-level perspectives for both men and women. European Urology. 2014;**65**:1211 https://www.ncbi.nlm.nih. gov/pubmed/24486308

[3] De Ridder D et al. Urgency and other lower urinary tract symptoms in men aged >/= 40 years: A Belgian epidemiological survey using the ICIQ-MLUTS questionnaire. International Journal of Clinical Practice. 2015;**69**:358 https://www.ncbi.nlm.nih.gov/ pubmed/25648652

[4] Taub DA et al. The economics of benign prostatic hyperplasia and lower urinary tract symptoms in the United States. Current Urology Reports. 2006;**7**:272 https://www.ncbi.nlm.nih. gov/pubmed/16930498

[5] Chapple C, Abrams P. Lower Urinary Tract Symptoms (LUTS): An International Consultation On Male LUTS. Societe Internationale d'Urologie (SIU). ISBN: 978-0-9877465-4-2

[6] Chapple CR et al. Lower urinary tract symptoms revisited: A broader clinical perspective. European Urology. 2008;**54**:563 https://www.ncbi.nlm.nih. gov/pubmed/18423969

[7] Gacci M et al. Metabolic syndrome and benign prostatic enlargement: A systematic review and meta-analysis. BJU International. 2015;**115**:24 https://www.ncbi.nlm.nih.gov/ pubmed/24602293

[8] Ficarra V et al. The role of inflammation in lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and its potential impact on medical therapy. Current Urology Reports. 2014;**15**:463 https://www.ncbi.nlm.nih.gov/ pubmed/25312251

[9] He Q et al. Metabolic syndrome, inflammation and lower urinary tract symptoms: Possible translational links. Prostate Cancer and Prostatic Diseases. 2016;**19**:7 https://www.ncbi.nlm.nih. gov/pubmed/26391088

[10] Drake MJ. Do we need a new definition of the overactive bladder syndrome? ICI-RS 2013. Neurourology and Urodynamics. 2014;**33**:622 http://www.ncbi.nlm.nih.gov/ pubmed/24838519

[11] Novara G et al. Critical review of guidelines for BPH diagnosis and treatment strategy. European Urology Supplements. 2006;**4**:418 http:// eu-acme.org/europeanurology/upload\_ articles/Novara2.pdf

[12] McVary KT et al. Update on AUA guideline on the management of benign prostatic hyperplasia. The Journal of Urology. 2011;**185**:1793 https://www. ncbi.nlm.nih.gov/pubmed/21420124

[13] Bosch J et al. Etiology, patient assessment and predicting outcome from therapy. International Consultation on Urological Diseases Male LUTS Guideline. 2013;**2013**:37

[14] Martin RM et al. Lower urinary tract symptoms and risk of prostate cancer: The HUNT 2 cohort, Norway. International Journal of Cancer. 2008;**123**:1924 https://www.ncbi.nlm. nih.gov/pubmed/18661522

[15] Young JM et al. Are men with lower urinary tract symptoms at increased risk of prostate cancer? A systematic review and critique of the available evidence. BJU International. 2000;**85**:1037 https://www.ncbi.nlm.nih.gov/ pubmed/10848691

[16] Donovan JL et al. Scoring the short form ICS male SF questionnaire. International continence society. The Journal of Urology. 2000;**164**:1948 https://www.ncbi.nlm.nih.gov/ pubmed/11061889

[17] Epstein RS et al. Validation of a new quality of life questionnaire for benign prostatic hyperplasia. Journal of Clinical Epidemiology. 1992;**45**:1431 https://www.ncbi.nlm.nih.gov/ pubmed/1281223

[18] Homma Y et al. Symptom assessment tool for overactive bladder syndrome--overactive bladder symptom score. Urology. 2006;**68**:318 https://www.ncbi.nlm.nih.gov/ pubmed/16904444

[19] Schou J et al. The value of a new symptom score (DAN-PSS) in diagnosing uro-dynamic infravesical obstruction in BPH. Scandinavian Journal of Urology and Nephrology. 1993;**27**:489 https://www.ncbi.nlm.nih. gov/pubmed/7512747

[20] Homma Y et al. Core lower urinary tract symptom score (CLSS) questionnaire: A reliable tool in the overall assessment of lower urinary tract symptoms. International Journal of Urology. 2008;**15**:816 https://www.ncbi. nlm.nih.gov/pubmed/18657204

[21] D'Silva KA et al. Does this man with lower urinary tract symptoms have bladder outlet obstruction?: The rational clinical examination: A systematic review. JAMA. 2014;**312**:535 https://www.ncbi.nlm.nih.gov/ pubmed/25096693

[22] Bryan NP et al. Frequency volume charts in the assessment and evaluation of treatment: How should we use them? European Urology. 2004;**46**:636 https://www.ncbi.nlm.nih.gov/ pubmed/15474275

[23] Salonia A et al. Is erectile dysfunction a reliable proxy of general male health status? The case for the international index of erectile functionerectile function domain. The Journal of Sexual Medicine. 2012;**9**:2708 https://www.ncbi.nlm.nih.gov/ pubmed/22897643

[24] Fisher WA et al. Erectile dysfunction (ED) is a shared sexual concern of couples I: Couple conceptions of ED. The Journal of Sexual Medicine. 2009;**6**:2746 https://www.ncbi.nlm.nih.gov/ pubmed/19694926

[25] Dong JY et al. Erectile dysfunction and risk of cardiovascular disease: Metaanalysis of prospective cohort studies. Journal of the American College of Cardiology. 2011;**58**:1378 https://www. ncbi.nlm.nih.gov/pubmed/21920268

[26] Gandaglia G et al. A systematic review of the association between erectile dysfunction and cardiovascular disease. European Urology. 2014;**65**:968 https://www.ncbi.nlm.nih.gov/ pubmed/24011423

[27] Gupta BP et al. The effect of lifestyle modification and cardiovascular risk factor reduction on erectile dysfunction: A systematic review and meta-analysis. Archives of Internal Medicine. 2011;**171**:1797 https://www.ncbi.nlm. nih.gov/pubmed/21911624

[28] Braun M et al. Epidemiology of erectile dysfunction: Results of the 'Cologne male survey. International Journal of Impotence Research. 2000;**12**:305 https://www.ncbi.nlm.nih. gov/pubmed/11416833

[29] Johannes CB et al. Incidence of erectile dysfunction in men 40 to 69

**119**

*Lower Urinary Tract Symptoms (LUTS) and Sexual Function and Dysfunction*

The multinational survey of the aging male (MSAM-7). European Urology. 2003;**44**:637 https://www.ncbi.nlm.nih.

[37] Molina Leyva A et al. Sexual dysfunction in psoriasis: A systematic review. Journal of the European Academy of Dermatology and

[38] Fan D et al. Male sexual dysfunction and ankylosing spondylitis: A systematic review and metaanalysis. The Journal of Rheumatology. 2015;**42**:252 https://www.ncbi.nlm.nih.gov/

[39] Duman DG et al. Nonalcoholic fatty liver disease is associated with erectile dysfunction: A prospective pilot study. The Journal of Sexual Medicine. 2016;**13**:383 https://www.ncbi.nlm.nih.

[40] Salonia A et al. Prevention and management of postprostatectomy sexual dysfunctions part 2: Recovery and preservation of erectile function, sexual desire, and orgasmic function. European Urology. 2012;**62**:273 https://www.ncbi.nlm.nih.gov/

[41] Salonia A et al. Prevention and management of postprostatectomy sexual dysfunctions. Part 1: Choosing the right patient at the right time for the right surgery. European Urology. 2012;**62**:261 https://www.ncbi.nlm.nih.

[42] Sanda MG et al. Quality of life and satisfaction with outcome among prostate-cancer survivors. The New England Journal of Medicine. 2008;**358**:1250 https://www.ncbi.nlm.

[43] Schauer I et al. Have rates of erectile dysfunction improved within the past

pubmed/25448789

gov/pubmed/26853046

pubmed/22575910

gov/pubmed/22575909

nih.gov/pubmed/18354103

Venereology. 2015;**29**:649 https://www. ncbi.nlm.nih.gov/pubmed/25424331

gov/pubmed/14644114

*DOI: http://dx.doi.org/10.5772/intechopen.86827*

years old: Longitudinal results from the Massachusetts male aging study. The Journal of Urology. 2000;**163**:460 https://www.ncbi.nlm.nih.gov/

[30] Schouten BW et al. Incidence rates of erectile dysfunction in the Dutch general population. Effects of definition, clinical relevance and duration of follow-up in the Krimpen study. International Journal of Impotence Research. 2005;**17**:58 https://www.ncbi.nlm.nih.gov/

[31] Jackson G et al. Cardiovascular aspects of sexual medicine. The Journal of Sexual Medicine. 2010;**7**:1608 https://www.ncbi.nlm.nih.gov/

[32] Binmoammar TA et al. The impact of poor glycaemic control on the prevalence of erectile dysfunction in men with type 2 diabetes mellitus: A systematic review. Journal of the Royal Society of Medicine Open. 2016;**7**:2054270415622602 https://www. ncbi.nlm.nih.gov/pubmed/26981254

[33] Glina S et al. Modifying risk factors to prevent and treat erectile dysfunction. The Journal of Sexual Medicine. 2013;**10**:115 https://www. ncbi.nlm.nih.gov/pubmed/22971247

[34] Vlachopoulos C et al. Erectile dysfunction in the cardiovascular patient. European Heart Journal. 2013;**34**:2034 https://www.ncbi.nlm.

[35] Seftel AD et al. Coexisting lower urinary tract symptoms and erectile dysfunction: A systematic review of epidemiological data. International Journal of Clinical Practice. 2013;**67**:32

https://www.ncbi.nlm.nih.gov/

[36] Rosen R et al. Lower urinary tract symptoms and male sexual dysfunction:

pubmed/23082930

nih.gov/pubmed/23616415

pubmed/10647654

pubmed/15510192

pubmed/20388161

*Lower Urinary Tract Symptoms (LUTS) and Sexual Function and Dysfunction DOI: http://dx.doi.org/10.5772/intechopen.86827*

years old: Longitudinal results from the Massachusetts male aging study. The Journal of Urology. 2000;**163**:460 https://www.ncbi.nlm.nih.gov/ pubmed/10647654

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

of treatment: How should we use them? European Urology. 2004;**46**:636

https://www.ncbi.nlm.nih.gov/

[23] Salonia A et al. Is erectile

[24] Fisher WA et al. Erectile dysfunction (ED) is a shared sexual concern of couples I: Couple conceptions of ED. The Journal of Sexual Medicine. 2009;**6**:2746 https://www.ncbi.nlm.nih.gov/

dysfunction a reliable proxy of general male health status? The case for the international index of erectile functionerectile function domain. The Journal of Sexual Medicine. 2012;**9**:2708 https://www.ncbi.nlm.nih.gov/

[25] Dong JY et al. Erectile dysfunction and risk of cardiovascular disease: Metaanalysis of prospective cohort studies. Journal of the American College of Cardiology. 2011;**58**:1378 https://www. ncbi.nlm.nih.gov/pubmed/21920268

[26] Gandaglia G et al. A systematic review of the association between erectile dysfunction and cardiovascular disease. European Urology. 2014;**65**:968

https://www.ncbi.nlm.nih.gov/

Archives of Internal Medicine. 2011;**171**:1797 https://www.ncbi.nlm.

[28] Braun M et al. Epidemiology of erectile dysfunction: Results of the 'Cologne male survey. International Journal of Impotence Research.

2000;**12**:305 https://www.ncbi.nlm.nih.

[29] Johannes CB et al. Incidence of erectile dysfunction in men 40 to 69

nih.gov/pubmed/21911624

gov/pubmed/11416833

[27] Gupta BP et al. The effect of lifestyle modification and cardiovascular risk factor reduction on erectile dysfunction: A systematic review and meta-analysis.

pubmed/24011423

pubmed/15474275

pubmed/22897643

pubmed/19694926

of prostate cancer? A systematic review and critique of the available evidence. BJU International. 2000;**85**:1037 https://www.ncbi.nlm.nih.gov/

[16] Donovan JL et al. Scoring the short form ICS male SF questionnaire. International continence society. The Journal of Urology. 2000;**164**:1948 https://www.ncbi.nlm.nih.gov/

[17] Epstein RS et al. Validation of a new quality of life questionnaire for benign prostatic hyperplasia. Journal of Clinical Epidemiology. 1992;**45**:1431

https://www.ncbi.nlm.nih.gov/

[18] Homma Y et al. Symptom

syndrome--overactive bladder symptom score. Urology. 2006;**68**:318 https://www.ncbi.nlm.nih.gov/

[19] Schou J et al. The value of a new symptom score (DAN-PSS) in diagnosing uro-dynamic infravesical obstruction in BPH. Scandinavian Journal of Urology and Nephrology. 1993;**27**:489 https://www.ncbi.nlm.nih.

[20] Homma Y et al. Core lower urinary tract symptom score (CLSS) questionnaire: A reliable tool in the overall assessment of lower urinary tract symptoms. International Journal of Urology. 2008;**15**:816 https://www.ncbi.

nlm.nih.gov/pubmed/18657204

https://www.ncbi.nlm.nih.gov/

[22] Bryan NP et al. Frequency volume charts in the assessment and evaluation

pubmed/25096693

[21] D'Silva KA et al. Does this man with lower urinary tract symptoms have bladder outlet obstruction?: The rational clinical examination: A systematic review. JAMA. 2014;**312**:535

assessment tool for overactive bladder

pubmed/10848691

pubmed/11061889

pubmed/1281223

pubmed/16904444

gov/pubmed/7512747

**118**

[30] Schouten BW et al. Incidence rates of erectile dysfunction in the Dutch general population. Effects of definition, clinical relevance and duration of follow-up in the Krimpen study. International Journal of Impotence Research. 2005;**17**:58 https://www.ncbi.nlm.nih.gov/ pubmed/15510192

[31] Jackson G et al. Cardiovascular aspects of sexual medicine. The Journal of Sexual Medicine. 2010;**7**:1608 https://www.ncbi.nlm.nih.gov/ pubmed/20388161

[32] Binmoammar TA et al. The impact of poor glycaemic control on the prevalence of erectile dysfunction in men with type 2 diabetes mellitus: A systematic review. Journal of the Royal Society of Medicine Open. 2016;**7**:2054270415622602 https://www. ncbi.nlm.nih.gov/pubmed/26981254

[33] Glina S et al. Modifying risk factors to prevent and treat erectile dysfunction. The Journal of Sexual Medicine. 2013;**10**:115 https://www. ncbi.nlm.nih.gov/pubmed/22971247

[34] Vlachopoulos C et al. Erectile dysfunction in the cardiovascular patient. European Heart Journal. 2013;**34**:2034 https://www.ncbi.nlm. nih.gov/pubmed/23616415

[35] Seftel AD et al. Coexisting lower urinary tract symptoms and erectile dysfunction: A systematic review of epidemiological data. International Journal of Clinical Practice. 2013;**67**:32 https://www.ncbi.nlm.nih.gov/ pubmed/23082930

[36] Rosen R et al. Lower urinary tract symptoms and male sexual dysfunction: The multinational survey of the aging male (MSAM-7). European Urology. 2003;**44**:637 https://www.ncbi.nlm.nih. gov/pubmed/14644114

[37] Molina Leyva A et al. Sexual dysfunction in psoriasis: A systematic review. Journal of the European Academy of Dermatology and Venereology. 2015;**29**:649 https://www. ncbi.nlm.nih.gov/pubmed/25424331

[38] Fan D et al. Male sexual dysfunction and ankylosing spondylitis: A systematic review and metaanalysis. The Journal of Rheumatology. 2015;**42**:252 https://www.ncbi.nlm.nih.gov/ pubmed/25448789

[39] Duman DG et al. Nonalcoholic fatty liver disease is associated with erectile dysfunction: A prospective pilot study. The Journal of Sexual Medicine. 2016;**13**:383 https://www.ncbi.nlm.nih. gov/pubmed/26853046

[40] Salonia A et al. Prevention and management of postprostatectomy sexual dysfunctions part 2: Recovery and preservation of erectile function, sexual desire, and orgasmic function. European Urology. 2012;**62**:273 https://www.ncbi.nlm.nih.gov/ pubmed/22575910

[41] Salonia A et al. Prevention and management of postprostatectomy sexual dysfunctions. Part 1: Choosing the right patient at the right time for the right surgery. European Urology. 2012;**62**:261 https://www.ncbi.nlm.nih. gov/pubmed/22575909

[42] Sanda MG et al. Quality of life and satisfaction with outcome among prostate-cancer survivors. The New England Journal of Medicine. 2008;**358**:1250 https://www.ncbi.nlm. nih.gov/pubmed/18354103

[43] Schauer I et al. Have rates of erectile dysfunction improved within the past

17 years after radical prostatectomy? A systematic analysis of the control arms of prospective randomized trials on penile rehabilitation. Andrology. 2015;**3**:661 https://www.ncbi.nlm.nih. gov/pubmed/26198796

[44] Ficarra V et al. Systematic review and meta-analysis of studies reporting potency rates after robot- assisted radical prostatectomy. European Urology. 2012;**62**:418 https://www.ncbi. nlm.nih.gov/pubmed/22749850

[45] Stolzenburg JU et al. Effect of surgical approach on erectile function recovery following bilateral nervesparing radical prostatectomy: An evaluation utilising data from a randomised, double-blind, doubledummy multicentre trial of tadalafil vs placebo. BJU International. 2015;**116**:241 https://www.ncbi.nlm.nih.gov/ pubmed/25560809

[46] Haglind E et al. Urinary incontinence and erectile dysfunction after robotic versus open radical prostatectomy: A prospective, controlled, nonrandomised trial. European Urology. 2015;**68**:216 https://www.ncbi.nlm.nih.gov/ pubmed/25770484

[47] Yaxley JW et al. Robot-assisted laparoscopic prostatectomy versus open radical retropubic prostatectomy: Early outcomes from a randomised controlled phase 3 study. Lancet. 2016;**388**:1057 https://www.ncbi.nlm.nih.gov/ pubmed/27474375

[48] Isgoren A et al. Erectile function outcomes after robot-assisted radical prostatectomy: Is it superior to open retropubic or laparoscopic approach. Sexual Medicine Reviews. 2014;**2**: 10-23. https://www.ncbi.nlm.nih.gov/ pubmed/27784540

[49] Glickman L et al. Changes in continence and erectile function between 2 and 4 years after radical prostatectomy. The Journal of Urology. 2009;**181**:731 https://www.ncbi.nlm.nih. gov/pubmed/19091349

[50] Incrocci L et al. Pelvic radiotherapy and sexual function in men and women. The Journal of Sexual Medicine. 2013;**10**(Suppl 1):53 https://www.ncbi. nlm.nih.gov/pubmed/23387912

[51] Stember DS et al. The concept of erectile function preservation (penile rehabilitation) in the patient after brachytherapy for prostate cancer. Brachytherapy. 2012;**11**:87 https://www.ncbi.nlm.nih.gov/ pubmed/22330103

[52] Cordeiro ER et al. High-intensity focused ultrasound (HIFU) for definitive treatment of prostate cancer. BJU International. 2012;**110**:1228 https://www.ncbi.nlm.nih.gov/ pubmed/22672199

[53] Williams SB et al. Comparative effectiveness of cryotherapy vs brachytherapy for localised prostate cancer. BJU International. 2012;**110**:E92 https://www.ncbi.nlm.nih.gov/ pubmed/22192688

[54] Hatzichristou D et al. Diagnosing sexual dysfunction in men and women: Sexual history taking and the role of symptom scales and questionnaires. The Journal of Sexual Medicine. 2016;**13**:1166 https://www.ncbi.nlm.nih. gov/pubmed/27436074

[55] Rosen RC et al. The process of care model for evaluation and treatment of erectile dysfunction. The process of care consensus panel. International Journal of Impotence Research. 1999;**11**:59-70. https://www.ncbi.nlm. nih.gov/pubmed/10356665

[56] Althof SE et al. Standard operating procedures for taking a sexual history. The Journal of Sexual Medicine. 2013;**10**:26 https://www.ncbi.nlm.nih. gov/pubmed/22970717

**121**

*Lower Urinary Tract Symptoms (LUTS) and Sexual Function and Dysfunction*

[65] Capogrosso P et al. One patient out of four with newly diagnosed erectile dysfunction is a young man- worrisome picture from the everyday clinical practice. The Journal of Sexual Medicine. 2013;**10**:1833 https://www. ncbi.nlm.nih.gov/pubmed/23651423

[66] Buvat J et al. Endocrine aspects of male sexual dysfunctions. The Journal of Sexual Medicine. 2010;**7**:1627

https://www.ncbi.nlm.nih.gov/

[67] Köhler TS, McVary KT. The relationship between erectile dysfunction and lower urinary tract symptoms and the role of phosphodiesterase type 5 inhibitors. European Urology. 2009;**55**:38-48

[68] Gacci M et al. Critical analysis of the relationship between sexual dysfunctions and lower urinary tract symptoms due to benign prostatic hyperplasia. European Urology.

[69] Rantell A et al. How does lower urinary tract dysfunction affect sexual function in men and women? ICI-RS 2015-part 1. Neurourology and

Urodynamics. 2017;**36**:949-952

[70] Giona S, Ganguly I, Muir G. Urologists' attitudes to sexual complications of LUTS/BPH

Urology. 2012;**61**(5):994-1003

[72] van Dijk MM, de la Rosette JJ, Michel MC. E ects of alpha (1)-adrenoceptor antagonists on male sexual function. Drugs.

treatments. World of Journal Urology.

[71] Gacci M, Corona G, Salvi M, et al. A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with α-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia. European

pubmed/20388162

2011;**60**:809-825

2018;**36**:1449-1145

2006;**66**:287-301

*DOI: http://dx.doi.org/10.5772/intechopen.86827*

[57] Rosen RC et al. The international index of erectile function (IIEF): A multidimensional scale for assessment of erectile dysfunction. Urology. 1997;**49**:822 https://www.ncbi.nlm.nih.

gov/pubmed/9187685

[58] World Health Organisation (ICD-10). International Statistical Classification of Diseases and Related Health Problems. Geneva: WHO; 1992

[59] McCabe MP et al. Definitions of sexual dysfunctions in women and men: A consensus statement from the fourth international consultation on sexual medicine 2015. The Journal of Sexual

[60] Graham CA. The DSM diagnostic criteria for female orgasmic disorder.

[61] Hatzichristou DG et al. Hemodynamic characterization of a functional erection: Arterial and corporeal veno-occlusive function in patients with a positive intracavernosal injection test. European

[62] Sikka SC et al. Standardization of vascular assessment of erectile dysfunction: Standard operating procedures for duplex ultrasound. The Journal of Sexual Medicine. 2013;**10**:120

https://www.ncbi.nlm.nih.gov/

[63] Glina S et al. SOP: Corpus cavernosum assessment

(cavernosography/cavernosometry). The Journal of Sexual Medicine. 2013;**10**:111 https://www.ncbi.nlm.nih.

Medicine. 2016;**13**(2):135-143

Archives of Sexual Behavior.

2010;**39**(2):256-270

Urology. 1999;**36**:60

pubmed/22970798

gov/pubmed/22971225

pubmed/20092443

[64] Hatzichristou D et al.

Recommendations for the clinical evaluation of men and women with sexual dysfunction. The Journal of Sexual Medicine. 2010;**7**:337 https://www.ncbi.nlm.nih.gov/

*Lower Urinary Tract Symptoms (LUTS) and Sexual Function and Dysfunction DOI: http://dx.doi.org/10.5772/intechopen.86827*

[57] Rosen RC et al. The international index of erectile function (IIEF): A multidimensional scale for assessment of erectile dysfunction. Urology. 1997;**49**:822 https://www.ncbi.nlm.nih. gov/pubmed/9187685

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

2009;**181**:731 https://www.ncbi.nlm.nih.

[50] Incrocci L et al. Pelvic radiotherapy and sexual function in men and women.

The Journal of Sexual Medicine. 2013;**10**(Suppl 1):53 https://www.ncbi. nlm.nih.gov/pubmed/23387912

[51] Stember DS et al. The concept of erectile function preservation (penile rehabilitation) in the patient after brachytherapy for prostate cancer. Brachytherapy. 2012;**11**:87 https://www.ncbi.nlm.nih.gov/

[52] Cordeiro ER et al. High-intensity focused ultrasound (HIFU) for

definitive treatment of prostate cancer. BJU International. 2012;**110**:1228 https://www.ncbi.nlm.nih.gov/

[53] Williams SB et al. Comparative effectiveness of cryotherapy vs brachytherapy for localised prostate cancer. BJU International. 2012;**110**:E92

https://www.ncbi.nlm.nih.gov/

[54] Hatzichristou D et al. Diagnosing sexual dysfunction in men and women: Sexual history taking and the role of symptom scales and questionnaires. The Journal of Sexual Medicine.

2016;**13**:1166 https://www.ncbi.nlm.nih.

[55] Rosen RC et al. The process of care model for evaluation and treatment of erectile dysfunction. The process of care consensus panel. International Journal of Impotence Research. 1999;**11**:59-70. https://www.ncbi.nlm.

[56] Althof SE et al. Standard operating procedures for taking a sexual history. The Journal of Sexual Medicine. 2013;**10**:26 https://www.ncbi.nlm.nih.

gov/pubmed/19091349

pubmed/22330103

pubmed/22672199

pubmed/22192688

gov/pubmed/27436074

nih.gov/pubmed/10356665

gov/pubmed/22970717

17 years after radical prostatectomy? A systematic analysis of the control arms of prospective randomized trials on penile rehabilitation. Andrology. 2015;**3**:661 https://www.ncbi.nlm.nih.

[44] Ficarra V et al. Systematic review and meta-analysis of studies reporting potency rates after robot- assisted radical prostatectomy. European Urology. 2012;**62**:418 https://www.ncbi.

nlm.nih.gov/pubmed/22749850

https://www.ncbi.nlm.nih.gov/

[46] Haglind E et al. Urinary incontinence and erectile dysfunction after robotic versus open radical prostatectomy: A prospective, controlled, nonrandomised trial. European Urology. 2015;**68**:216 https://www.ncbi.nlm.nih.gov/

[47] Yaxley JW et al. Robot-assisted laparoscopic prostatectomy versus open radical retropubic prostatectomy: Early outcomes from a randomised controlled phase 3 study. Lancet. 2016;**388**:1057 https://www.ncbi.nlm.nih.gov/

[48] Isgoren A et al. Erectile function outcomes after robot-assisted radical prostatectomy: Is it superior to open retropubic or laparoscopic approach. Sexual Medicine Reviews. 2014;**2**: 10-23. https://www.ncbi.nlm.nih.gov/

[49] Glickman L et al. Changes in continence and erectile function between 2 and 4 years after radical prostatectomy. The Journal of Urology.

pubmed/25560809

pubmed/25770484

pubmed/27474375

pubmed/27784540

[45] Stolzenburg JU et al. Effect of surgical approach on erectile function recovery following bilateral nervesparing radical prostatectomy: An evaluation utilising data from a randomised, double-blind, doubledummy multicentre trial of tadalafil vs placebo. BJU International. 2015;**116**:241

gov/pubmed/26198796

**120**

[58] World Health Organisation (ICD-10). International Statistical Classification of Diseases and Related Health Problems. Geneva: WHO; 1992

[59] McCabe MP et al. Definitions of sexual dysfunctions in women and men: A consensus statement from the fourth international consultation on sexual medicine 2015. The Journal of Sexual Medicine. 2016;**13**(2):135-143

[60] Graham CA. The DSM diagnostic criteria for female orgasmic disorder. Archives of Sexual Behavior. 2010;**39**(2):256-270

[61] Hatzichristou DG et al. Hemodynamic characterization of a functional erection: Arterial and corporeal veno-occlusive function in patients with a positive intracavernosal injection test. European Urology. 1999;**36**:60

[62] Sikka SC et al. Standardization of vascular assessment of erectile dysfunction: Standard operating procedures for duplex ultrasound. The Journal of Sexual Medicine. 2013;**10**:120 https://www.ncbi.nlm.nih.gov/ pubmed/22970798

[63] Glina S et al. SOP: Corpus cavernosum assessment (cavernosography/cavernosometry). The Journal of Sexual Medicine. 2013;**10**:111 https://www.ncbi.nlm.nih. gov/pubmed/22971225

[64] Hatzichristou D et al. Recommendations for the clinical evaluation of men and women with sexual dysfunction. The Journal of Sexual Medicine. 2010;**7**:337 https://www.ncbi.nlm.nih.gov/ pubmed/20092443

[65] Capogrosso P et al. One patient out of four with newly diagnosed erectile dysfunction is a young man- worrisome picture from the everyday clinical practice. The Journal of Sexual Medicine. 2013;**10**:1833 https://www. ncbi.nlm.nih.gov/pubmed/23651423

[66] Buvat J et al. Endocrine aspects of male sexual dysfunctions. The Journal of Sexual Medicine. 2010;**7**:1627 https://www.ncbi.nlm.nih.gov/ pubmed/20388162

[67] Köhler TS, McVary KT. The relationship between erectile dysfunction and lower urinary tract symptoms and the role of phosphodiesterase type 5 inhibitors. European Urology. 2009;**55**:38-48

[68] Gacci M et al. Critical analysis of the relationship between sexual dysfunctions and lower urinary tract symptoms due to benign prostatic hyperplasia. European Urology. 2011;**60**:809-825

[69] Rantell A et al. How does lower urinary tract dysfunction affect sexual function in men and women? ICI-RS 2015-part 1. Neurourology and Urodynamics. 2017;**36**:949-952

[70] Giona S, Ganguly I, Muir G. Urologists' attitudes to sexual complications of LUTS/BPH treatments. World of Journal Urology. 2018;**36**:1449-1145

[71] Gacci M, Corona G, Salvi M, et al. A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with α-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia. European Urology. 2012;**61**(5):994-1003

[72] van Dijk MM, de la Rosette JJ, Michel MC. E ects of alpha (1)-adrenoceptor antagonists on male sexual function. Drugs. 2006;**66**:287-301

[73] Roehrborn CG, Siami P, Barkin J, et al. The in uence of baseline parameters on changes in international prostate symp- tom score with dutasteride, tamsulosin, and combination therapy among men with symptomatic benign prostatic hyperplasia and an enlarged prostate: 2-year data from the CombAT study. European Urology. 2009;**55**:461-471

[74] Roehrborn CG, Boyle P, Nickel JC, et al. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology. 2002;**60**:434-441

[75] Roehrborn CG, Siami P, Barkin J, et al. The e ects of dutas- teride, tamsulosin and combination therapy on lower urinary tract symptoms in men with benign prostatic hyperplasia and pros- tatic enlargement: 2-year results from the CombAT study. The Journal of Urology. 2008;**179**:616-621

[76] McConnell JD, Roehrborn CG, Bautista OM, et al. The long-term e ect of doxazosin, nasteride, and combination ther- apy on the clinical progression of benign prostatic hyperplasia. The New England Journal of Medicine. 2003;**349**:2387-2398

[77] Roehrborn CG, Siami P, Barkin J, et al. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. European Urology. 2010;**83**:227-237;57:123-131

[78] Naslund MJ, Miner M. A review of the clinical efficacy and safety of 5alpha-reductase inhibitors for the enlarged prostate. Clinical Therapeutics. 2007;**29**(1):17-25

[79] Madersbacher S, Marberger M. Is transurethral resection of the prostate still justified? BJU International. 1999

[80] McConnell JD, Barry MJ, Bruskewitz RC. Benign prostatic hyperplasia: Diagnosis and treatment In: (AHCPR) AfHCPaR (ed), Clinical Practice Guideline Quick Reference, Guide for Clinicians. 1994;**8**:1-17

[81] Emberton M, Neal DE, Black N, et al. The effect of prostatectomy on symptom severity and quality of life. British Journal of Urology. 1996;**77**:233-247

[82] Horasanli K, Silay MS, Altay B, Tanriverdi O, Sarica K, Miroglu C. Photoselective potassium titanyl phosphate (KTP) laser vaporization versus transurethral resection of the prostate for prostates larger than 70 ml: A short-term prospective randomized trial. Urology. 2008;**71**:247-251

[83] Alivizatos G, Skolarikos A, Chalikopoulos D, et al. Transurethral photoselective vaporization versus transvesical open enucleation for prostatic adenomas >80 ml: 12-mo results of a randomized prospective study. European Urology. 2008;**54**:427-437

[84] Bouchier-Hayes DM, Anderson P, Van Appledorn S, Bugeja P, Costello AJ. KTP laser versus transurethral resection: Early results of a randomized trial. Journal of Endourology. 2006;**20**:580-585

[85] Naspro R, Suardi N, Salonia A, et al. Holmium laser enucleation of the prostate versus open prostatectomy for prostates >70 g: 24-month follow-up. European Urology. 2006;**50**:563-568

[86] Briganti A, Naspro R, Gallina A, et al. Impact on sexual function of holmium laser enucleation versus transurethral resection of the prostate: Results of a prospective, 2-center, randomized trial. The Journal of Urology. 2006;**175**:1817-1821

[87] Tabatabaei S, Choi B, Muir G. 2272 ejaculation-preserving

**123**

*Lower Urinary Tract Symptoms (LUTS) and Sexual Function and Dysfunction*

activity in the bladder. Endocrinology.

[94] Fibbi B, Morelli A, Vignozzi L, et al. Characterization of phosphodiesterase type 5 expression and functional activity in the human male lower urinary tract. The Journal of Sexual Medicine. 2010;**7**(1 Pt 1):59-69

[95] Morelli A, Filippi S, Comeglio P, et al. Acute vardenal administration improves bladder oxygenation in spontaneously hypertensive rats. The Journal of Sexual Medicine. 2010;**7**(1 Pt 1):107-120

[96] Morelli A, Sarchielli E, Comeglio P,

et al. Phosphodiesterase type 5 expression in human and rat lower urinary tract tissues and the effect of tadalafil on prostate gland oxygenation in spontaneously hypertensive rats. The Journal of Sexual Medicine.

[97] McVary KT, Roehrborn CG, Kaminetsky JC, et al. Tadalafil

secondary to benign prostatic hyperplasia. The Journal of Urology.

relieves lower urinary tract symptoms

[98] İrer B et al. Evaluation of sexual dysfunction, lower urinary tract symptoms and quality of life in men with obstructive sleep apnea syndrome and the efficacy of continuous positive airway pressure therapy. Urology.

[99] Miyazato M, Tohyama K, Touyama M, et al. Effect of continuous positive airway pressure on nocturnal urine production in patients with obstructive sleep apnea syndrome. Neurourology and Urodynamics. 2017;**36**:376-379

[100] Campos-Juanatey FF, Fernandez-Barriales M, Gonzalez M, Portillo-Martin JA. Effects of obstructive sleep apnea and its treatment over the erectile function: A systematic review. Asian Journal of Andrology. 2017;**19**:303-310

2011;**8**(10):2746-2760

2007;**177**(4):1401-1407

2018;**121**:86-92

2007;**148**(3):1019-1029

*DOI: http://dx.doi.org/10.5772/intechopen.86827*

photo-selective vaporization of prostate (EP-PVP): Six years experience from a multi-Centre study. The Journal of

[88] Kim M, Song SH, Ku JH, Kim HJ, Paick JS. Pilot study of the clinical efficacy of ejaculatory hood sparing technique for ejaculation preservation in holmium laser enucleation of the prostate. International Journal of Impotence Research. 2014;**27**:20-24

[89] Bruskewitz R, Issa MM, Roehrborn CG, et al. A prospective, randomized 1-year clinical trial comparing transurethral needle ablation to transurethral resection of the prostate for the treatment of symptomatic benign prostatic hyperplasia. The Journal of Urology. 1998;**159**:1588-1593

[90] Hill B, Belville W, Bruskewitz R, et al. Transurethral needle ablation versus transurethral resection of the prostate for the treatment of symptomatic benign prostatic hyperplasia: 5-year results of a

prospective, randomized, multicenter clinical trial. The Journal of Urology.

[91] Cimentepe E, Unsal A, Saglam R. Randomized clinical trial comparing transurethral needle ablation with transurethral resection of the prostate for the treatment of benign prostatic hyperplasia: Results at 18 months. Journal of Endourology/Endourological

[92] Woo HH, Chin PT, McNicholas TA, et al. Safety and feasibility of the prostatic urethral lift: A novel, minimally invasive treatment for lower urinary tract symptoms

(LUTS) secondary to benign prostatic hyperplasia (BPH). BJU International.

[93] Filippi S, Morelli A, Sandner P, et al. Characterization and functional role of androgen-dependent PDE5

2004;**171**:2336-2340

Society. 2003;**17**:103

2011;**108**:82-88

Urology. 2011;**185**:e910-e911

*Lower Urinary Tract Symptoms (LUTS) and Sexual Function and Dysfunction DOI: http://dx.doi.org/10.5772/intechopen.86827*

photo-selective vaporization of prostate (EP-PVP): Six years experience from a multi-Centre study. The Journal of Urology. 2011;**185**:e910-e911

*Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice*

[80] McConnell JD, Barry MJ, Bruskewitz RC. Benign prostatic hyperplasia: Diagnosis and treatment In: (AHCPR) AfHCPaR (ed), Clinical Practice Guideline Quick Reference, Guide for Clinicians. 1994;**8**:1-17

[81] Emberton M, Neal DE, Black N, et al. The effect of prostatectomy on symptom severity and quality of life. British Journal of Urology.

[82] Horasanli K, Silay MS, Altay B, Tanriverdi O, Sarica K, Miroglu C. Photoselective potassium titanyl phosphate (KTP) laser vaporization versus transurethral resection of the prostate for prostates larger than 70 ml: A short-term prospective randomized

trial. Urology. 2008;**71**:247-251

[83] Alivizatos G, Skolarikos A, Chalikopoulos D, et al. Transurethral photoselective vaporization versus transvesical open enucleation for

prostatic adenomas >80 ml: 12-mo results of a randomized prospective study. European Urology. 2008;**54**:427-437

[84] Bouchier-Hayes DM, Anderson P, Van Appledorn S, Bugeja P, Costello AJ.

resection: Early results of a randomized

KTP laser versus transurethral

trial. Journal of Endourology.

[85] Naspro R, Suardi N, Salonia A, et al. Holmium laser enucleation of the prostate versus open prostatectomy for prostates >70 g: 24-month follow-up. European Urology. 2006;**50**:563-568

[86] Briganti A, Naspro R, Gallina A, et al. Impact on sexual function of holmium laser enucleation versus transurethral resection of the prostate: Results of a prospective, 2-center, randomized trial. The Journal of Urology. 2006;**175**:1817-1821

[87] Tabatabaei S, Choi B, Muir G. 2272 ejaculation-preserving

2006;**20**:580-585

1996;**77**:233-247

[73] Roehrborn CG, Siami P, Barkin J, et al. The in uence of baseline parameters on changes in international prostate symp- tom score with dutasteride, tamsulosin, and combination therapy among men with symptomatic benign prostatic hyperplasia and an enlarged prostate: 2-year data from the CombAT study. European Urology. 2009;**55**:461-471

[74] Roehrborn CG, Boyle P, Nickel JC, et al. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology.

[75] Roehrborn CG, Siami P, Barkin J, et al. The e ects of dutas- teride,

Urology. 2008;**179**:616-621

[76] McConnell JD, Roehrborn CG, Bautista OM, et al. The long-term e ect of doxazosin, nasteride, and combination ther- apy on the clinical progression of benign prostatic hyperplasia. The New England Journal of Medicine. 2003;**349**:2387-2398

[77] Roehrborn CG, Siami P, Barkin J, et al. The effects of combination therapy with dutasteride and

tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. European Urology.

[78] Naslund MJ, Miner M. A review of the clinical efficacy and safety of 5alpha-reductase inhibitors for the enlarged prostate. Clinical Therapeutics.

[79] Madersbacher S, Marberger M. Is transurethral resection of the prostate still justified? BJU International. 1999

2010;**83**:227-237;57:123-131

2007;**29**(1):17-25

tamsulosin and combination therapy on lower urinary tract symptoms in men with benign prostatic hyperplasia and pros- tatic enlargement: 2-year results from the CombAT study. The Journal of

2002;**60**:434-441

**122**

[88] Kim M, Song SH, Ku JH, Kim HJ, Paick JS. Pilot study of the clinical efficacy of ejaculatory hood sparing technique for ejaculation preservation in holmium laser enucleation of the prostate. International Journal of Impotence Research. 2014;**27**:20-24

[89] Bruskewitz R, Issa MM, Roehrborn CG, et al. A prospective, randomized 1-year clinical trial comparing transurethral needle ablation to transurethral resection of the prostate for the treatment of symptomatic benign prostatic hyperplasia. The Journal of Urology. 1998;**159**:1588-1593

[90] Hill B, Belville W, Bruskewitz R, et al. Transurethral needle ablation versus transurethral resection of the prostate for the treatment of symptomatic benign prostatic hyperplasia: 5-year results of a prospective, randomized, multicenter clinical trial. The Journal of Urology. 2004;**171**:2336-2340

[91] Cimentepe E, Unsal A, Saglam R. Randomized clinical trial comparing transurethral needle ablation with transurethral resection of the prostate for the treatment of benign prostatic hyperplasia: Results at 18 months. Journal of Endourology/Endourological Society. 2003;**17**:103

[92] Woo HH, Chin PT, McNicholas TA, et al. Safety and feasibility of the prostatic urethral lift: A novel, minimally invasive treatment for lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). BJU International. 2011;**108**:82-88

[93] Filippi S, Morelli A, Sandner P, et al. Characterization and functional role of androgen-dependent PDE5

activity in the bladder. Endocrinology. 2007;**148**(3):1019-1029

[94] Fibbi B, Morelli A, Vignozzi L, et al. Characterization of phosphodiesterase type 5 expression and functional activity in the human male lower urinary tract. The Journal of Sexual Medicine. 2010;**7**(1 Pt 1):59-69

[95] Morelli A, Filippi S, Comeglio P, et al. Acute vardenal administration improves bladder oxygenation in spontaneously hypertensive rats. The Journal of Sexual Medicine. 2010;**7**(1 Pt 1):107-120

[96] Morelli A, Sarchielli E, Comeglio P, et al. Phosphodiesterase type 5 expression in human and rat lower urinary tract tissues and the effect of tadalafil on prostate gland oxygenation in spontaneously hypertensive rats. The Journal of Sexual Medicine. 2011;**8**(10):2746-2760

[97] McVary KT, Roehrborn CG, Kaminetsky JC, et al. Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia. The Journal of Urology. 2007;**177**(4):1401-1407

[98] İrer B et al. Evaluation of sexual dysfunction, lower urinary tract symptoms and quality of life in men with obstructive sleep apnea syndrome and the efficacy of continuous positive airway pressure therapy. Urology. 2018;**121**:86-92

[99] Miyazato M, Tohyama K, Touyama M, et al. Effect of continuous positive airway pressure on nocturnal urine production in patients with obstructive sleep apnea syndrome. Neurourology and Urodynamics. 2017;**36**:376-379

[100] Campos-Juanatey FF, Fernandez-Barriales M, Gonzalez M, Portillo-Martin JA. Effects of obstructive sleep apnea and its treatment over the erectile function: A systematic review. Asian Journal of Andrology. 2017;**19**:303-310

### *Edited by Ran Pang*

Lower urinary tract dysfunction (LUTD) is an umbrella diagnosis that covers the abnormalities of anatomy and function in the bladder, urethra, and, in men, the prostate. People with LUTD face a number of social, mental, and physical health effects due to the symptoms. Despite the increasing evidence in the assessment and management of lower urinary tract symptoms, it remains a challenge to bridge the gap between research evidence and clinical practice. In this book, each and every one of the authors presents a remarkable work for how to apply the evidence to clinical practice from different aspects. I hope this book is a key for every reader to open the door to LUTD.

Published in London, UK © 2020 IntechOpen © Sinhyu / iStock

Lower Urinary Tract Dysfunction - From Evidence to Clinical Practice

Lower Urinary Tract

Dysfunction

From Evidence to Clinical Practice

*Edited by Ran Pang*