**Meet the editor**

He is actively involved in colorectal surgical training as well as in academic supervision of postgraduate research doctorate degrees. His contributions to the medical literature include over 180 peer reviewed primary publications and 26 textbook chapters. He is associate editor for International Surgery and chairman of the editorial board for Techniques in Coloproctology, Yik-

Hong is a member of several medical societies and is presently the World Corporate Secretary of the International College of Surgeons.

### Contents

### **Preface XI**

	- **Part 2 Laparoscopic Colorectal Surgery 55**
	- **Part 3 Emergency Colorectal Surgery 73**
	- **Part 4 Postoperative Follow-Up 87**

### Preface

The practice of colorectal surgery is a rapidly evolving discipline which continually seeks to evaluate and incorporate new emerging technological advances and management concepts into routine day to day practice. This is necessary to achieve continued excellence in service delivery, particularly for patients with complex problems. When these techniques and concepts eventually withstand the robust testing of wide-spread routine surgical practice, they become assimilated into traditional textbooks. Nonetheless, there is a time lag because traditional textbooks require substantial time in production and readership distribution which is something that the on-line electronic medium overcomes, particularly when the latter is focused on selected key topics.

In recent years, significant progress in colorectal surgery has been made which includes laparoscopic techniques, pre-operative management, emergency colorectal surgery, fast track multimodal recovery, management of complex wound problems and colorectal cancer follow-up. "Contemporary Issues in Colorectal Surgical Practice" aims to bridge the gap between the journal article and the traditional textbook in these areas.

> **Dr. Yik-Hong Ho**  Professor & Head of Surgery, School of Medicine & Dentistry, James Cook University, Townsville, Australia

## **Part 1**

**Perioperative Management** 

## **Preoperative Preparation in Colorectal Surgery**

### Arne-Christian Mohn

*Haugesund Hospital, Helse Fonna HF Norway* 

### **1. Introduction**

In august 1954 Robert J. Gosling Read said at the 59th Annual Convention of the National Medical Association, Washington, D.C: "…Through the personal knowledge of the patient's life history and interest he (*the good family physician*) has offered advice based on common sense rather than specialized training. This is the concept of accelerated recovery…"

This was the first time in the literature the concept was used. Interesting enough, several points of today's enhanced recovery are also common sense since all items are not evidence based. Evidence-based medicine is defined as the integration of best research evidence with clinical expertise and patient values to optimise clinical outcomes and quality of life.1

The concept returned in surgery in 1990. Krohn et al2 published from Good Samaritan Hospital in Los Angeles a four days discharge from hospital after open-heart surgery. He called it rapid sustained recovery. This was the first paper on enhanced recovery after surgery (ERAS).

In 1994 Hartford Hospital and Baystate Medical Center3 introduced the term "fast-track surgery" which included 1: preoperative education, 2: early extubation, 3: methylprednisolon sodium succinate before surgery followed by dexamethasone for 24 hours postoperatively, 4: prophylactic digitalization, metoclopramide HCL, docusate sodium, and ranitidine HAL, 5: accelerated rehabilitation, 6: early discharge, 7: a dedicated fast-track coordinator to perform both daily telephone contact and a 1-week postoperative examination and 8: a routine 1-month postoperative visit with a PA or MD. This showed a systematically control of all patients and a multimodal focus to enhance the recovery time. But all the interventions were not evidence based and the study was an observational study.

Why didn't the literature focus on recovery before1990?

One reason was that until the 1980´s the preoperative preparation was optimizing the organ function medically to tolerate the narcosis, bowel preparation to avoid anastigmatic leakage and infection and disinfection of the surgeons' hands and the patients' skin. There were no systematic antibiotics given, no thrombi-prophylaxis and no epidural anaesthetics.

Another reason was the lack of methodical trials and evidence based medicine on ancillary procedures. Variations in surgical procedures and peri-operative care have been recognised since the early 1980s and are generally interpreted as evidence of uncertainty among practitioners regarding optimal care.4 How different surgeons or hospitals provided the procedures varied enormously, leading to and "expertise bias". They tended to be accepted with little question and which, fore some surgeons, had become indispensible rituals. Most of the surgery was done the way you learned it from your mentor. He had his own meaning based on his experience and a standard saying was: "In our hospital we do it my way" or said by Edmund Burke: "custom reconciles us to everything."

Further, randomised trials to peri-operative care questions were often difficult or impractical to perform. A valid randomised controlled trial may also be impossible in many circumstances and may limit the generalisability of the results.

 In the 1990s there was a change. The main reason was the specialization. Earlier the surgeon did the anaesthetics themselves, but today we have specialists in this area, which make us treat patients. The securing of a safe anaesthesia during operations is more important than ever before, partly because of the mere number of operations, and partly because of the greater extent to which other operative risks — haemorrhage, shock and infection — have been overcome. The risk from the anaesthetic is now so very small that the joint aim of the surgeon and anaesthetist to abolish it altogether is not far from being accomplished.5 The specialty of anaesthesia has seen major advances thanks to the development of safer anaesthetic agents, improved knowledge of pain physiology and pain management, and incorporation of a better understanding of peri-operative patho-physiology into peri-operative care. Concomitantly, development of minimally invasive surgery has further reduced stress responses and pain, thereby providing potential for enhanced recovery. However, an increasing proportion of elderly patients with organ dysfunction have led to demands for further reductions in postoperative complications and the costs of treating them.

The transition from inpatient surgery to ambulatory procedures has proceeded at a rate that was unthinkable a few decades ago, but could all surgical procedures ultimately be done on an outpatient basis?6 The forthcoming years will, as before, pose several challenges for anaesthetists to improve peri-operative care and to take part in the multidisciplinary collaboration of fast-track surgery. Anaesthetists should consider the development of "perioperative medicine" as a multidisciplinary effort that should not involve conflict between the anaesthetic and surgical specialities, but rather serve as a mutual platform for improvement of peri-operative care. All together there are more and more emphasis on the joint aim: peri-operative preparations and recovery.

Through the 1980´s and the 1990´s, evidence based medicine became the state of the art, but still it is troublesome to change the way of thinking.

### **2. ERAS**

Kehlet et al gave some answers to these questions in 19977: He focused on the improvements on the administration of opioid analgesics in new ways, such as continuous or on demand intravenous or epidural infusion. These methods allowed lower total opioid dosages, provided a more stable concentration of opioid and correspondingly better analgesic effects, and also fewer unwanted side effects. The introduction of rapid short acting volatile anaesthetics, opioids, and muscle relaxants also facilitated expansion of ambulatory surgery for minor to moderate procedures. The emphasis on ambulatory surgery and accelerated surgical stay programs, both with a focus on early recovery of organ function and provision of functional analgesia, provided an opportunity for a reappraisal of opioid use in these settings. However, the same techniques may be used to facilitate early recovery and

with little question and which, fore some surgeons, had become indispensible rituals. Most of the surgery was done the way you learned it from your mentor. He had his own meaning based on his experience and a standard saying was: "In our hospital we do it my way" or

Further, randomised trials to peri-operative care questions were often difficult or impractical to perform. A valid randomised controlled trial may also be impossible in many

 In the 1990s there was a change. The main reason was the specialization. Earlier the surgeon did the anaesthetics themselves, but today we have specialists in this area, which make us treat patients. The securing of a safe anaesthesia during operations is more important than ever before, partly because of the mere number of operations, and partly because of the greater extent to which other operative risks — haemorrhage, shock and infection — have been overcome. The risk from the anaesthetic is now so very small that the joint aim of the surgeon and anaesthetist to abolish it altogether is not far from being accomplished.5 The specialty of anaesthesia has seen major advances thanks to the development of safer anaesthetic agents, improved knowledge of pain physiology and pain management, and incorporation of a better understanding of peri-operative patho-physiology into peri-operative care. Concomitantly, development of minimally invasive surgery has further reduced stress responses and pain, thereby providing potential for enhanced recovery. However, an increasing proportion of elderly patients with organ dysfunction have led to demands for further reductions in

The transition from inpatient surgery to ambulatory procedures has proceeded at a rate that was unthinkable a few decades ago, but could all surgical procedures ultimately be done on an outpatient basis?6 The forthcoming years will, as before, pose several challenges for anaesthetists to improve peri-operative care and to take part in the multidisciplinary collaboration of fast-track surgery. Anaesthetists should consider the development of "perioperative medicine" as a multidisciplinary effort that should not involve conflict between the anaesthetic and surgical specialities, but rather serve as a mutual platform for improvement of peri-operative care. All together there are more and more emphasis on the

Through the 1980´s and the 1990´s, evidence based medicine became the state of the art, but

Kehlet et al gave some answers to these questions in 19977: He focused on the improvements on the administration of opioid analgesics in new ways, such as continuous or on demand intravenous or epidural infusion. These methods allowed lower total opioid dosages, provided a more stable concentration of opioid and correspondingly better analgesic effects, and also fewer unwanted side effects. The introduction of rapid short acting volatile anaesthetics, opioids, and muscle relaxants also facilitated expansion of ambulatory surgery for minor to moderate procedures. The emphasis on ambulatory surgery and accelerated surgical stay programs, both with a focus on early recovery of organ function and provision of functional analgesia, provided an opportunity for a reappraisal of opioid use in these settings. However, the same techniques may be used to facilitate early recovery and

said by Edmund Burke: "custom reconciles us to everything."

circumstances and may limit the generalisability of the results.

postoperative complications and the costs of treating them.

joint aim: peri-operative preparations and recovery.

still it is troublesome to change the way of thinking.

**2. ERAS** 

decreased need for prolonged monitoring and stay in recovery and high dependency wards after major procedures.

The key factors that keep a patient in hospital after uncomplicated abdominal surgery include the need of parenteral analgesia (persisting pain), intravenous fluid (persisting gut function), and bed rest (persisting lack of mobility).8 ERAS change the way of thinking to minimal these factors.

Traditionally the complication rate in colorectal surgery is between 20-40%. The hospital stay is between one and two weeks.9,10 Early clinical pathways had showed reduced length of stay in major surgery.11 Kehlet published his first results8,12,13 with a hospital stay of two days after colonic surgery. He established the concept accelerated recovery and started to compile an interest group, which later became the ERAS-group. Studies showed reduction in hospital stay, reducing ileus and cardiopulmonary complications.10,13-23 Also in rectal cancer surgery the peri-operative "fast-track" multimodal rehabilitation program is effective and safe.24,25 Randomised controlled trials (RCT) have showed the same results,19,20,22,23,27-29 though Behrns patients were discharged on liquid diets.

Advances in peri-operative patho-physiology have indicated multi-factorial reasons for post-operative morbidity30, length of stay and patient recovery. It is therefore required to deal with these causes by multifaceted interventions. First of all, the patient's medication must be optimized according to organ function like cardiac disease, chronic obstructive lung disease, diabetes mellitus etc. Further the patient must be evaluated according to malnutrition. Malnutrition can prolong the stress response and increase the likelihood of complications. Likewise, heavy drinkers and smokers should abstain from alcohol and smoking a month before surgery if possible. Otherwise they have higher incidence of complications. Thereafter the treatment should focus on pain relief, reducing stress response and reducing nausea and vomiting. Further on the patients should avoid hypothermia, immobilization and semi-starvation. Finally, the postoperative ileus should be minimized. There are reasons to believe that including as many ERAS elements as possible in a clinical pathway may result in a cumulative effect and contribute to enhanced recovery in patients.31

The major premise behind fast-track surgery is that patients regain function more rapidly and that this allows a reduction in the period during which the patient is unable to perform activities of daily living.21

Better adherence to the elements of the ERAS protocol is crucial to improve surgical outcome. Nearly all, preoperative and per-operative ERAS interventions, influenced postoperative outcomes beneficially.32 Patients with high adherence to the ERAS protocol had a 25% lower risk of postoperative complications and nearly 50% lower risk of postoperative symptoms delaying discharge. They also had a higher tendency toward reaching length of stay within the target limits compared with patients operated on under less optimal ERAS protocol adherence. As the enhanced recovery field develops, certain interventions may turn out to be nonessential. However, before omitting specific components in the protocol, such a decision should be based on a closer understanding of the importance of each element in the program.

Many of the peri-operative interventions that have been widely adopted into clinical practice are supported by very limited evidence. For a number of interventions the data are either limited in quantity or quality, or are inconsistent. Systematic reviews should be


\*EDA = epidural anaesthesia, \$PCA = patient-controlled anaesthesia, #PONV = postoperative nausea and vomiting, %TIVA = total intravenous aenesthesia

Table 1. **Elements of ERAS (Enhanced Recovery After Surgery)**

Preoperative information Oral and written information to patients and relatives.

Bowel preparation No bowel preparation is necessary before colon surgery.

Admission The day before or operation day. Oral supplements given at home before admission. Preoperative fasting Fasting only 2 hours before surgery, food and milk rinks 6

Carbohydrate loading Drinks the evening before (800ml) and 2-3 hours before

Preoperative medication Paracetamol (1g x 4) reduces postoperative pain,

Preoperative anticoagulation No-risk – no anticoagulation. Moderate-risk once a day at

Preoperative antibiotics Oral and intravenous or intravenous only. Cephalosporins

PONV Peroperative and early postoperative oxygen. On moderate-

og TIVA and dexamethasone.

Urinary drainage 1 day after colon surgery and about 3 days after low-rectal

Postoperative ileus Complex aetiology with many contributors, but opioids

Mobilization Out of bed operation day and 6 hours the day after and

\*EDA = epidural anaesthesia, \$PCA = patient-controlled anaesthesia, #PONV = postoperative nausea

exacerbate the ileus

the day after.

thereafter

Table 1. **Elements of ERAS (Enhanced Recovery After Surgery)**

Nasogastric tubes Have no place routinely in elective colorectal surgery Peroperative normothermia Normothermia during surgery, reduces wound infections

Alvimopan (12mg x2) reduces postoperative ileus

(2g) or combination doxycycline (0,4g) and metronidazol

Mid-thoracic EDA\* during surgery (bolus and continous infusion) and EDA or PCA**\$** postoperatively for 2-3 days

risk TIVA% or an antiemetic drug. In high-risk combination

least 5 days. High-risk once a day 28 days

reduces PONV**#**, ileus, pain, and hospital stay.

Restricted, goal-directed fluid therapy is preferably

No need in colon surgery. In rectal surgery still needed.

Oral intake 4 hours after surgery and normal food intake

Preparation still before rectal surgery.

after surgery.

hours before.

(1,5g).

Surgical incisions Less is better, laparoscopy even best.

surgery

surgery (400ml)

Achieve patient management. Patient education before and

**Elements Guidelines** 

Preoperative epidural

Postoperative fluid

Drainage of the abdominal

Postoperative nutritional

and vomiting, %TIVA = total intravenous aenesthesia

anaesthesia

management

acity

care

conducted with the same methodological rigour expected for randomised controlled trials. Systematic reviews conducted under the auspices of Cochrane Collaboration have an established methodology and peer review process, and they may be less prone to bias than non-Cochrane systematic reviews.1

There is supportive evidence from studies that enhanced recovery programs should be considered as standard peri-operative care.33 Still, there are controversies. Metaanalysis,31,34,35 show reduction of complications, but not major complications. There may be a decrease, but it is not statistical significant. One reason may be the lack of robust RCT's. The reduction of hospital stay is real and the readmission rate does not increase. However, a Bayesian meta-analysis showed significant reduction in hospital stay, complications and no difference in readmission rates and mortality.36 A Bayesian model has a number of advantages like full allowance for all parameter uncertainty, the ability to include other pertinent information that would otherwise be excluded, and the ability to extend the models to accommodate more complex, but frequent occurring, scenarios.37

The debate is still going and the conclusion is unclear, but ERAS should be considered the new standard. The markedly shortened hospital stay in fast-track rehabilitation should change the capacity of operative departments considerably. At the same time denotes the implementation of fast-track rehabilitation a paradigm shift away from invasive postoperative monitoring and regulation attempts of today's intensive care medicine to intensified pain therapy and reinforced physical rehabilitation.

Today the ERAS-group has consensus guidelines. They recommend as many elements as possible (for instance 17 out of 20), but as mentioned above – still several elements are highly debatable. We will therefore in this chapter discuss the elements mentioned in Table 1, to see if there are evidence today to change the way of preparing the patients and go into the next area: Optimize the preparation, peri-operative treatment, the logistics and the recovery.

But first, we will look at the concepts stress response and insulin resistance.

### **3. Stress response and insulin resistance**

Surgical stress response is a major contributing factor to postoperative morbidity. Advances in surgical technique and peri-operative management the last years have allowed better control of the stress response intra-operatively and improved patient outcome.

Surgical stress response is mediated via neuro-endocrine mechanisms leading to alterations in protein homeostasis (increased catabolism), hyper-metabolism, altered carbohydrate metabolism (increased gluconeogenesis and insulin resistance) and increased lipolysis.20

The underlying hypothesis is that the reaction to a physical stress depends in part on the metabolic state at the onset of the stress. In many of its features, postoperative insulin resistance resembles type 2-diabetes mellitus. The reduction in insulin sensitivity develops after surgery in patients with and without type 2 diabetes.38

A state of insulin resistance has been confirmed in several different types of stress, including burn injury, accident trauma, and sepsis. During the 1990s studies of insulin resistance in elective surgery have been performed.39 The degree of postoperative insulin resistance was significantly correlated with the length of stay postoperatively. The duration of surgery was closely associated to the relative decrease in whole body insulin sensitivity. These findings suggest that the relative change in insulin sensitivity is related to the degree of surgical stress.40

### **4. Preoperative information**

It is very important to inform both the patient and relatives days before the surgery. An effective implementation and a consequent huge rate of compliance are essential in terms of achieving uniformity of patient management. A thorough information orally and a written preadmission information describing what will happen during their hospital stay, what they have to expect, and what their role in their recovery, are essential.8,41 The success relies on the patients understanding and appreciating their responsibilities.42 Preoperative education may reduce anxiety and aid in coping, generally enhancing postoperative recovery with an earlier return of gastrointestinal motility after surgery.43,44 Some patients require extensive education in issues relating to stoma care, self-monitoring for signs of dehydration, and sexual function. This education starts before operation and continues after the operation.45

It is well established that intensive preoperative patient information can facilitate postoperative recovery and pain relief, particularly in patients who exhibit most denial and the highest level of anxiety.9 Teaching the patient to cope with pain and the importance of pain control and the expectation of some degree of nausea are important task to understand before surgery. Patients should also understand the importance of getting out of bed the evening of the operation or the envisioned discharge on the third or fourth postoperative day.

Further on an evaluation of the home environment is important beforehand. In that way it is easier to plan an early, realistic discharge day. Family or caregiver support is crucial to ensure a safe transition from hospital to home and to decrease the risk of readmission.

A cornerstone in the achievement is motivated surgeons, anaesthesiologists and study nurses.9,46 Fast-track surgery requires a multidisciplinary, concentrated and coordinated effort, with nurses as essential to the success of these programs.47,48 The dedicated and motivated team consists of anaesthesiologists, surgeons, residents, dieticians, physiotherapists, social workers, dieticians, and nursing team. The nurses should concentrate on individual tasks and spend much time on managing complications as they occur. They must challenge the traditional nursing practices and expend this role to avoid that patients become passive recipients of care. The nurses partner with the patient to achieve well-defined goals to improve patient's outcome.

Changes also need to be made to organisational strategies and the medical professionals involved in pre, intra and especially postoperative care require support, perhaps via continuing education.47 A protocol is not enough and the importance of this collaboration has been widely described.5,9,11,13,19,46,49-51


### **5. Bowel preparation**

8 Contemporary Issues in Colorectal Surgical Practice

significantly correlated with the length of stay postoperatively. The duration of surgery was closely associated to the relative decrease in whole body insulin sensitivity. These findings suggest that the relative change in insulin sensitivity is related to the degree of surgical

It is very important to inform both the patient and relatives days before the surgery. An effective implementation and a consequent huge rate of compliance are essential in terms of achieving uniformity of patient management. A thorough information orally and a written preadmission information describing what will happen during their hospital stay, what they have to expect, and what their role in their recovery, are essential.8,41 The success relies on the patients understanding and appreciating their responsibilities.42 Preoperative education may reduce anxiety and aid in coping, generally enhancing postoperative recovery with an earlier return of gastrointestinal motility after surgery.43,44 Some patients require extensive education in issues relating to stoma care, self-monitoring for signs of dehydration, and sexual function. This education starts before operation and

It is well established that intensive preoperative patient information can facilitate postoperative recovery and pain relief, particularly in patients who exhibit most denial and the highest level of anxiety.9 Teaching the patient to cope with pain and the importance of pain control and the expectation of some degree of nausea are important task to understand before surgery. Patients should also understand the importance of getting out of bed the evening of the operation or the envisioned discharge on the third or

Further on an evaluation of the home environment is important beforehand. In that way it is easier to plan an early, realistic discharge day. Family or caregiver support is crucial to ensure a safe transition from hospital to home and to decrease the risk of readmission.

A cornerstone in the achievement is motivated surgeons, anaesthesiologists and study nurses.9,46 Fast-track surgery requires a multidisciplinary, concentrated and coordinated effort, with nurses as essential to the success of these programs.47,48 The dedicated and motivated team consists of anaesthesiologists, surgeons, residents, dieticians, physiotherapists, social workers, dieticians, and nursing team. The nurses should concentrate on individual tasks and spend much time on managing complications as they occur. They must challenge the traditional nursing practices and expend this role to avoid that patients become passive recipients of care. The nurses partner with the patient to

Changes also need to be made to organisational strategies and the medical professionals involved in pre, intra and especially postoperative care require support, perhaps via continuing education.47 A protocol is not enough and the importance of this collaboration

 Orally and written information to reduce anxiety and postoperative pain Achieve patient management and avoid passive recipients of care

achieve well-defined goals to improve patient's outcome.

has been widely described.5,9,11,13,19,46,49-51

stress.40

**4. Preoperative information** 

continues after the operation.45

fourth postoperative day.

It was unquestionably a great convenience to the surgeon to operate on an empty bowel rather than on one loaded with faeces. It was also supposed through a century that operations on the bowel, especially those involving a suture line or an anatomises, were safer and less likely to be associated with gross contamination and sepsis if the intestine is in a relatively or completely empty condition.52 The assumption, which formed the basis for the practice of mechanical bowel preparation prior to major colorectal surgery, was so widely accepted as sensible and logical, that nobody saw the need of any really stringent scrutiny. Until recently it was thought that vigorous preoperative mechanical cleansing of the bowel (mechanical bowel preparation), together with the use of oral antibiotics, reduced the risk of septic complications after non-emergency (elective) colorectal operations. Mechanical bowel preparation was performed routinely prior to colorectal surgery until 1972, when this procedure started to be questioned. Even though ES Hughes in 197253 concluded in a randomised clinical study that vigorous mechanical preparation was not necessary, most surgeons continued the bowel cleansing until late 1980s.

But in the late 1980s some started to question the necessity of bowel cleansing when using intravenous antibiotics.54 The cleansing was time consuming and associated with discomfort. Even though Burke55 stated that bowel preparation does not influence outcome after elective colorectal surgery and a review concluded with limited evidence in the literature to support the use of mechanical bowel preparation56, still until late 1990s it was standard along with antibiotics preoperatively. The question wasn't answered until two well-designed randomized clinical trials were performed and printed in The Lancet and Br J Surg in 2007.57,58

Reviews and meta-analysis cannot show higher leakage rate with than without bowel preparation. Some studies and even meta-analysis have shown the opposite with higher frequencies after preparation,59,60 but the evidence based answer today is that there are no differences and therefore it is not necessary with any preparations before colon surgery.61 It is too early to conclude on rectal surgery, so still one may do the preparation before the surgery here. Further research on mechanical bowel preparation or enemas versus no preparation in patients submitted for elective rectal surgery and laparoscopic colorectal surgery is warranted.

There are also some controversies about what kind of preparation to use. No bowel preparation method meets the ideal criteria for bowel cleansing prior to surgery. The new generation of bowel purgatives include oral sodium phosphate preparations and polyethylene glycol-electrolyte lavage solutions. Both are well tolerated by the patients with the oral sodium phosphate preparation as the most preferred because of less fluid to drink for the patients and possibly more effective,62,63 but there are still some safety issues without a clear solution. Both cleansing methods make some electrolyte disturbances even though it seems like the polyethylene glycol-electrolyte lavage solutions are less dangerous.64 Therefore adequate hydration is important before, during, and after bowel preparation.65

Furthermore, in children and elderly, patients with kidney disease or decreased intravascular volume, and those using medicines that affect renal perfusion or function (diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and possibly non-steroidal anti-inflammatory drugs (NSAIDs)) should not use oral sodium phosphate. There is a possibility to develop acute phosphate nephropathy. They should instead use polyethylene glycol-electrolyte lavage solutions.66


### **6. Admission**

Earlier the patients admitted to the hospital two days before surgery. On the admission day they were given a full liquid diet, and on the day before surgery, a clear liquid diet. Bowel cleansing was given the day before.

Today the history of the patient and co-morbidity are evaluated in an outpatient manner by the surgeon and the anaesthetist. The oral carbohydrate feeding and/or protein feeding are done home by the patient. It is a common view that nutritional support in the peri-operative phase is associated with decreased morbidity, particularly in severely nutritionally depleted patients.9,67 Patients receiving oral nutritional supplements over an extended peri-operative period lost significantly less weight than those who received no supplements or postoperative supplements only. The incidence of minor complications was significantly lower than in those receiving no supplements or preoperative supplements only. The benefit of outcome occurred independently of nutritional status.68

The use of laxatives is still debatable, as the standard measure of return of bowel function would be the ability to tolerate oral feeding rather than just bowel movement.31

The patient, at home, may handle the injection of anti-coagulant, the evening before surgery. If the patient lives distant from the hospital, he can be admitted the day before surgery or stay at a hospital hotel.


### **7. Preoperative fasting and carbohydrate loading**

The overnight fasting routine was first suggested in 1848 after Hannah Greener's death in Winlaton, as a result of the first reported death following general anesthesia.69 Later the same century it was suggested that a better preparation for the patient was to allow a cup of tea or beef tea some hours before the operation.70 In the early 1900s, reports of complications from aspirations resulted in the strict recommendation of nil by mouth.66 General anaesthetic reduces reflexes that stop regurgitated gastric juices reaching the lungs. As this can be dangerous, people were often advised to have nothing to eat or drink from the midnight before surgery.

The main reason for questioning the nil by mouth rules was to improve patient's well being, by reducing thirst and for caffeine drinkers avoiding headaches from withdrawal symptoms. Norway was the first country to adopt new guidelines in 1993, the Norwegian Consensus Guidelines for preoperative fasting in elective surgery, and a national survey was performed three years later, which showed no increase in aspirations due to the new routines.72 Fasting before general anaesthesia aims to reduce the volume and acidity of

sodium phosphate. There is a possibility to develop acute phosphate nephropathy. They

Earlier the patients admitted to the hospital two days before surgery. On the admission day they were given a full liquid diet, and on the day before surgery, a clear liquid diet. Bowel

Today the history of the patient and co-morbidity are evaluated in an outpatient manner by the surgeon and the anaesthetist. The oral carbohydrate feeding and/or protein feeding are done home by the patient. It is a common view that nutritional support in the peri-operative phase is associated with decreased morbidity, particularly in severely nutritionally depleted patients.9,67 Patients receiving oral nutritional supplements over an extended peri-operative period lost significantly less weight than those who received no supplements or postoperative supplements only. The incidence of minor complications was significantly lower than in those receiving no supplements or preoperative supplements only. The benefit

The use of laxatives is still debatable, as the standard measure of return of bowel function

The patient, at home, may handle the injection of anti-coagulant, the evening before surgery. If the patient lives distant from the hospital, he can be admitted the day before surgery or

The overnight fasting routine was first suggested in 1848 after Hannah Greener's death in Winlaton, as a result of the first reported death following general anesthesia.69 Later the same century it was suggested that a better preparation for the patient was to allow a cup of tea or beef tea some hours before the operation.70 In the early 1900s, reports of complications from aspirations resulted in the strict recommendation of nil by mouth.66 General anaesthetic reduces reflexes that stop regurgitated gastric juices reaching the lungs. As this can be dangerous, people were often advised to have nothing to eat or drink from the

The main reason for questioning the nil by mouth rules was to improve patient's well being, by reducing thirst and for caffeine drinkers avoiding headaches from withdrawal symptoms. Norway was the first country to adopt new guidelines in 1993, the Norwegian Consensus Guidelines for preoperative fasting in elective surgery, and a national survey was performed three years later, which showed no increase in aspirations due to the new routines.72 Fasting before general anaesthesia aims to reduce the volume and acidity of

would be the ability to tolerate oral feeding rather than just bowel movement.31

Patients receive and administrate oral nutrition supplements at home

should instead use polyethylene glycol-electrolyte lavage solutions.66

No need for bowel preparation in colon surgery

of outcome occurred independently of nutritional status.68

**7. Preoperative fasting and carbohydrate loading** 

Admission the day before or operation day

Still need in rectal surgery

cleansing was given the day before.

**6. Admission** 

stay at a hospital hotel.

midnight before surgery.

stomach contents during surgery, thus reducing the risk of regurgitation-/aspiration.73 Recent guidelines have recommended a shift in fasting policy from the standard 'nil by mouth from midnight' approach to more relaxed policies, which permit a period of restricted fluid intake up to 2 hours before surgery. Food or drinks containing milk make the emptying slower and need six hours.74,75 Emptying of the stomach usually occurs within less than 90 minutes in elective patients after consumption of clear fluids, and after a 12,5% carbohydrate loaded drink 120 minutes.76

Practice has been slow to change. There was no evidence to suggest a shortened fluid fast results in an increased risk of aspiration, regurgitation or related morbidity compared with the standard 'nil by mouth from midnight' fasting policy. Permitting patients to drink water preoperatively resulted in significantly lower gastric volumes. Clinicians should be encouraged to appraise this evidence for themselves and when necessary adjust any remaining standard fasting policies (nil-by-mouth from midnight) for patients that are not considered 'at-risk' during anaesthesia. Some people are considered more likely to regurgitate under anaesthetic, including those who are pregnant, elderly, and obese or have stomach disorders. More research is needed to determine whether these people can also safely drink up to a few hours before surgery.75

Beverages including water, tea, coffee, or juices without fruit meat cannot be expected to cause any major changes in metabolism, and thus, even with the new and more liberal fasting guidelines, the patient will be operated in a metabolic state of fasting. Infusions of carbohydrates before elective abdominal surgery were shown to improve postoperative insulin sensitivity.77 Carbohydrate feeding given shortly before elective colorectal surgery displayed less reduced insulin sensitivity (reduced insulin resistance) after surgery compared to patients who were operated after an overnight fast40 and not associated with aspiration.78

The patients were given 800 ml 12,5% carbohydrate drink (malto-dextrin) the evening before the operation and another 400 ml about 2-3 hours before the operation. Insulin resistance has been shown to be an independent factor explaining the variation in length of stay.79 This study showed that preparation with a carbohydrate-rich drink increased preoperative wellbeing compared with intake of placebo (water) or overnight fasting. These drinks lead to reduced anxiety and significantly reduced postoperative hospital stay, and a trend towards earlier return of gut function when compared with fasting or supplementary water.8,32,38,80 This earlier return of bowel function may be a contributory factor for shorter hospital stay. Consumption of an appropriate potion composed of water, minerals and carbohydrates offers some protection against surgical trauma in terms of metabolic status, cardiac function and psychosomatic status.


### **8. Preoperative medication**

Patients should not receive pre-anaesthetic anxiolytic or analgesic medication.8 Paracetamol used, as preoperative medication to reduce postoperative pain is well established. The use of diclofenac to strengthen the effect (postoperatively) has caused unwanted side effects both in animal studies and retrospective clinical studies.81 This study showed significant more anastomotic leakages. Therefore it is recommended to use other non-steroid antiinflammatory drugs or opioid antagonists like Alvimopan.

Alvimopan is a novel, oral, peripherally acting antagonist, a µ-opioid receptor that has limited ability to cross the blood-brain barrier and is currently being evaluated for the management of postoperative ileus.82 The use is 12 mg 2 hours before surgery and then twice daily beginning on first postoperative day until hospital discharge or for a maximum of 7 days of postoperative treatment. Alvimopan act within the gastrointestinal tract and does not affect the centrally mediated analgesia. Alvimopan significantly accelerate gastrointestinal recovery in bowel resection patients; reduce postoperative morbidity rates, hospital stay, and rates of hospital readmission83 with a mean daily opioid consumption of 26 mg. However, opioids provide better pain control compared with other analgesics such as anti-inflammatory drugs.

Glucocorticoids (GCs) are well known for their analgesic, anti-inflammatory, immunemodulating, and antiemetic effects, although the mechanisms by which glucocorticoids exert their action are far from clarified.84 Preoperative GCs decrease complications including infectious complications specifically and length of stay after major abdominal surgery. Although inflammation is a necessary precursor for healing, it is the excessive amplitude of the inflammatory response after major abdominal surgery that is thought to contribute to postoperative morbidity and delay recovery. GCs do not seem to increase the risk of complications in colorectal surgery.85 As an intervention; administration of GCs is inexpensive and simple allowing for clinical implementation without difficulty. Earlier there was not found a significant effect or no effect on postoperative nausea and vomiting and pain in studies. In the concept of enhanced recovery, the effects have been found84 but Fukami et al found no effect in a randomized controlled trial86 Another trial found that 8 mg dexamethasone preoperatively has no significant effect on reducing postoperative inflammatory response and also does not improve outcomes of colorectal surgery.87

The analgesic effects of GCs are provided through inhibition of the phospholipase enzyme and accordingly blockage of both the cyclooxygenase and the lipoxygenase pathway in the inflammatory chain reaction. The mechanism by which GCs alleviate nausea and vomiting is not fully understood, but the effects are probably centrally mediated via inhibition of prostaglandin synthesis or inhibition of the release of endogenous opioids.

Postoperative fatigue appears to be an important problem following only certain forms of surgery. Preoperative administration of dexamethasone resulted in a significant reduction in early postoperative fatigue, associated with an attenuated early peritoneal cytokine response. Peritoneal production of cytokines may therefore be important in postoperative recovery.88 The reduction in fatigue was moderate and was associated with a diminished peritoneal pro-inflammatory cytokine reaction on day 1, supporting the hypothesis that peritoneal inflammation is an important contributor to fatigue after major abdominal surgery.

Because of divergence in the trials, we need larger randomised trials before we can recommend the use of GCs before surgery.


### **9. Preoperative anticoagulation**

12 Contemporary Issues in Colorectal Surgical Practice

more anastomotic leakages. Therefore it is recommended to use other non-steroid anti-

Alvimopan is a novel, oral, peripherally acting antagonist, a µ-opioid receptor that has limited ability to cross the blood-brain barrier and is currently being evaluated for the management of postoperative ileus.82 The use is 12 mg 2 hours before surgery and then twice daily beginning on first postoperative day until hospital discharge or for a maximum of 7 days of postoperative treatment. Alvimopan act within the gastrointestinal tract and does not affect the centrally mediated analgesia. Alvimopan significantly accelerate gastrointestinal recovery in bowel resection patients; reduce postoperative morbidity rates, hospital stay, and rates of hospital readmission83 with a mean daily opioid consumption of 26 mg. However, opioids provide better pain control compared with other analgesics such

Glucocorticoids (GCs) are well known for their analgesic, anti-inflammatory, immunemodulating, and antiemetic effects, although the mechanisms by which glucocorticoids exert their action are far from clarified.84 Preoperative GCs decrease complications including infectious complications specifically and length of stay after major abdominal surgery. Although inflammation is a necessary precursor for healing, it is the excessive amplitude of the inflammatory response after major abdominal surgery that is thought to contribute to postoperative morbidity and delay recovery. GCs do not seem to increase the risk of complications in colorectal surgery.85 As an intervention; administration of GCs is inexpensive and simple allowing for clinical implementation without difficulty. Earlier there was not found a significant effect or no effect on postoperative nausea and vomiting and pain in studies. In the concept of enhanced recovery, the effects have been found84 but Fukami et al found no effect in a randomized controlled trial86 Another trial found that 8 mg dexamethasone preoperatively has no significant effect on reducing postoperative

inflammatory response and also does not improve outcomes of colorectal surgery.87

prostaglandin synthesis or inhibition of the release of endogenous opioids.

The analgesic effects of GCs are provided through inhibition of the phospholipase enzyme and accordingly blockage of both the cyclooxygenase and the lipoxygenase pathway in the inflammatory chain reaction. The mechanism by which GCs alleviate nausea and vomiting is not fully understood, but the effects are probably centrally mediated via inhibition of

Postoperative fatigue appears to be an important problem following only certain forms of surgery. Preoperative administration of dexamethasone resulted in a significant reduction in early postoperative fatigue, associated with an attenuated early peritoneal cytokine response. Peritoneal production of cytokines may therefore be important in postoperative recovery.88 The reduction in fatigue was moderate and was associated with a diminished peritoneal pro-inflammatory cytokine reaction on day 1, supporting the hypothesis that peritoneal inflammation is an important contributor to fatigue after major abdominal

Because of divergence in the trials, we need larger randomised trials before we can

inflammatory drugs or opioid antagonists like Alvimopan.

as anti-inflammatory drugs.

surgery.

recommend the use of GCs before surgery.

 Paracetamol given preoperatively reduce postoperative pain Alvimopan is an alternative to reduce postoperative ileus

Venous thrombo-embolism (VTE) is the most common preventable cause of death in surgical patients. Thrombo-prophylaxis, using mechanical methods to promote venous outflow from the legs and antithrombotic drugs, provides the most effective means of reducing morbidity and mortality in these patients. Despite the evidence supporting thrombo-prophylaxis, it remains underused. The reasons for its underuse are not fully understood, but those having abdominal surgery are often considered to be at a lower risk than orthopaedic patients. In addition, there are still concerns about an increased risk of bleeding complications.89,90

The overall incidence of venous trombo-embolism (VTE) without anticoagulation is 20-25% for patients more than 40 years old in general surgery. For patients having cancer, the incidence slightly rise to 30-40%.89-93 Fatal embolism occurred in about 1%. After low molecular weight heparin (LMWH) the incidence of VTE is 6% and fatal embolism 0,01%.92,94,95 Complication rates are low and should not prevent the use of prophylaxis in most patients.91 Patients undergoing surgery of the large bowel and the rectum have a considerable risk of developing vascular complications expressed as venous thrombosis and/or thrombosis in the lungs (pulmonary embolism). These complications can lead to lifelong impaired venous function in the legs or occasionally sudden postoperative death. The clinical importance of asymptomatic proximal and distal deep vein thrombosis (DVT) remains uncertain and controversial. Unrecognised DVT may lead to long-term morbidity from post-phlebitic syndrome and predispose patients to recurrent VTE. Because VTE in hospitalized patients often is asymptomatic, it is inappropriate to rely on early diagnosis. Furthermore, non-invasive tests, such as compression ultrasonography, have limited sensitivity for a diagnosis of asymptomatic DVT. The high mortality rate in patients with asymptomatic proximal DVT underscores its clinical relevance and supports asymptomatic proximal DVT as an appropriate endpoint in clinical trials.96,97 Thrombo-prophylaxis is, therefore, the most effective strategy to reduce morbidity and mortality from VTE in surgical patients. Low-dose unfractioned heparin (UFH) and LMWH appear to be equally effective and safe in this patient group, and either agent can be used. Because patients with underlying cancer are at higher risk, it is reasonable for them to use elastic stockings in conjunction with these agents.

The advantage of LMWH is that it can be administered once daily and it is less likely to cause heparin-induced thrombocytopenia and thrombosis than standard heparin preparations. Among the most important risk factors are a previous history of thrombotic disease, advanced age (risk levels increase above 40 years), prolonged immobility, and coexisting cancer and its treatment.90

In low-risk patients, who undergoing minor or relatively short operations, are less than 40 years old and with no additional risk factors, no prophylaxis is necessary except early and frequent mobilization.

In moderate-risk patients who are more than 40 years old and undergoing major surgery with no additional risk factors, LMWH given once daily (>3,400 anti-Xa Units) or graduated compression stockings used properly, is sufficient for at least 5 days.98

In high-risk patients more than 40 years old with additional risk factors, LMWH given once daily supplied with graduated compression stockings may be sufficient. But the length of anticoagulation has been discussed. A review demonstrates that this combined treatment also is effective within the high-risk group of patients undergoing surgery of the large bowel or rectum.97

In addition to ensuring optimal timing for the initiation of prophylaxis, it is also important to establish the duration of prophylaxis. A review suggests that prophylaxis should be administered for at least one month after surgery.99 The ENOXACAN II study showed, at least in high-risk patients, a significant benefit of an extended 4-week prophylactic period compared with the standard 1-week regimen, with no increase in adverse effects, confirmed by a meta-analysis.87,100,101 It is now some evidence that late thrombotic events can occur up to 6-7 weeks after operation.90 Even if there are no difference in mortality, the patients with lower limb DVTs have almost 60% higher relative risk of suffering from post-thrombotic syndrome. Furthermore there are associations between higher 90 days mortality and asymptomatic proximal DVT, which explain the large number of fatal pulmonary emboli in autopsy series.

In laparoscopic surgery and fast-track surgery there are not any RCTs to tell if it is sufficient to give the prophylaxis for a shorter period. Until then one must carefully include selected high-risk patients, major cancer surgery or they who have previously had VTE, to continuing thrombo-prophylaxis after hospital discharge with LMWH for up to 28 days.

It should be emphasized that epidural analgesia per se reduces thrombo-embolic complications by 50% in lower body procedures, but this has not been demonstrated after abdominal procedures.8


### **10. Preoperative antibiotics**

Without any prophylactic antibiotics, one may consider more than 40% wound infections after colorectal surgery, or at least 27% found by Raahave et al102 with extensive bowel cleansing. In that case it is unethical to operate without any coverage as pointed out in the first meta-analysis on the field.103 The conclusions were that the chosen antibiotics were not the crucial point, but the timing, coverage and duration were the most important variables. The latest Cochrane Analysis confirms this.104

The antibiotics must cover the copious mixture of both anaerobic and aerobic species, which are in the large intestinum. 104 The optimal drug should be one that is not used as a rst-line choice in the treatment of surgical infection. But the most common drug used worldwide is cephalosporin, which also is used in the treatment of infections. However, doxycycline, used in Scandinavians studies105,106 and still used in Scandinavia, is not an antibiotic commonly used in the treatment of established surgical infection, nor is it prominently associated with causing C. difcile colitis, and it is not expensive. But to cover the anaerobic agents, doxycycline is given together with metronidazol with the same limitations as cephalosporin. Doxycycline has not been studied extensively in comparison to other established gold-

In high-risk patients more than 40 years old with additional risk factors, LMWH given once daily supplied with graduated compression stockings may be sufficient. But the length of anticoagulation has been discussed. A review demonstrates that this combined treatment also is effective within the high-risk group of patients undergoing surgery of the large bowel

In addition to ensuring optimal timing for the initiation of prophylaxis, it is also important to establish the duration of prophylaxis. A review suggests that prophylaxis should be administered for at least one month after surgery.99 The ENOXACAN II study showed, at least in high-risk patients, a significant benefit of an extended 4-week prophylactic period compared with the standard 1-week regimen, with no increase in adverse effects, confirmed by a meta-analysis.87,100,101 It is now some evidence that late thrombotic events can occur up to 6-7 weeks after operation.90 Even if there are no difference in mortality, the patients with lower limb DVTs have almost 60% higher relative risk of suffering from post-thrombotic syndrome. Furthermore there are associations between higher 90 days mortality and asymptomatic proximal DVT, which explain the large number of fatal pulmonary emboli in autopsy series. In laparoscopic surgery and fast-track surgery there are not any RCTs to tell if it is sufficient to give the prophylaxis for a shorter period. Until then one must carefully include selected high-risk patients, major cancer surgery or they who have previously had VTE, to continuing thrombo-prophylaxis after hospital discharge with LMWH for up to 28 days.

It should be emphasized that epidural analgesia per se reduces thrombo-embolic complications by 50% in lower body procedures, but this has not been demonstrated after

In moderate-risk patients LMWH once daily or compression stockings, 5 days

In high-risk patients LMWH supplied with stockings recommended for up to 28 days

Without any prophylactic antibiotics, one may consider more than 40% wound infections after colorectal surgery, or at least 27% found by Raahave et al102 with extensive bowel cleansing. In that case it is unethical to operate without any coverage as pointed out in the first meta-analysis on the field.103 The conclusions were that the chosen antibiotics were not the crucial point, but the timing, coverage and duration were the most important variables.

The antibiotics must cover the copious mixture of both anaerobic and aerobic species, which are in the large intestinum. 104 The optimal drug should be one that is not used as a rst-line choice in the treatment of surgical infection. But the most common drug used worldwide is cephalosporin, which also is used in the treatment of infections. However, doxycycline, used in Scandinavians studies105,106 and still used in Scandinavia, is not an antibiotic commonly used in the treatment of established surgical infection, nor is it prominently associated with causing C. difcile colitis, and it is not expensive. But to cover the anaerobic agents, doxycycline is given together with metronidazol with the same limitations as cephalosporin. Doxycycline has not been studied extensively in comparison to other established gold-

or rectum.97

abdominal procedures.8

**10. Preoperative antibiotics** 

The latest Cochrane Analysis confirms this.104

In low-risk patients no prophylaxis is necessary

standard antibiotic recommendations, but perhaps it should be. According to timing it is well accepted that one hour before surgery is optimal and there is no need for a second dosage because of increased risk of resistant organisms and Clostridium difficile colitis. A combination of oral and intravenous antibiotics seemed to be better than intravenous only, but because of current recommendations before surgery; it should probably be given intravenously.


### **11. Preoperative Epidural Anaesthesia (EDA)**

Prevention and treatment of postoperative pain is the central goal of interdisciplinary anaesthetists and surgeons. The use of epidural anaesthesia is not for pain control only. Effective analgesia reduces the intensity of autonomous and somatic reflexes, but of importance is the blockade of afferent fibres from the surgical site in order to positively modulate posttraumatic stress reaction either by peripheral nerve blockade, spinal or epidural analgesia.41 It leads to a modification of the endocrine metabolic action after major surgical procedures, whilst postoperative inflammation is not affected. Mid–thoracic epidural activated before the onset of surgery also blocks stress hormone release and attenuates postoperative insulin resistance.8

Both afferent pain fibres and sympathetic efferent fibres contribute to ileus. Because postoperative pain activates the autonomic system and indirectly causes adverse effects on various organ systems, blockage of these pain signals both intra-operatively and postoperatively with epidural anaesthesia and analgesia can blunt the stress response and minimize the effect of surgery on bowel motility.107,108 There is experimental evidence that the sympathectomy produced by local anaesthetics is associated with increased gastrointestinal blood flow. Shortened duration of postoperative ileus after abdominal operations using these techniques may be translated into decreased length of stay and patient satisfaction.109

Regional anaesthesia and analgesia, particularly neural blockade, produce a host of benefits for surgical patients, accelerates recovery of organ function including gastrointestinal and pulmonary function, decreased cardiovascular demands, superior pain relief, reduce the amount of general anaesthetic used (allowing faster recovery), and allows intensified early mobilisation.49,107,110 Administration of epidural local anaesthetics to patients undergoing laparotomy reduces gastrointestinal paralysis compared with systemic or epidural opioids, with comparable postoperative pain relief. Addition of opioid to epidural local anaesthetic may provide superior postoperative analgesia with activity compared with epidural local anaesthetics alone, and can be accomplished with less toxicity than either class of drug.1,109- 111 The activation of nociceptive afferent and sympathetic efferent nerves are believed to reduce pain and peri-operative opioid requirements, which may lead to reduced postoperative nausea and vomiting (PONV).

Most important may be the significant and prolonged response in the stress response when the epidural anaesthesia is continued postoperatively. To produce the benefit reliably, it appears that epidural analgesia with local anaesthetics should be instituted before the surgical stress and continued until postoperative ileus has resolved, typically 2-3 days later. This perioperative analgesia may contribute to lower risk of death after surgery. The low risk of serious adverse consequences suggest that many high-risk patients undergoing major intra-abdominal surgery will receive substantial benefit from combined general and epidural anaesthesia intraoperatively with continuing postoperatively epidural analgesia.112,113 The effect of additional epidural opioid on gastrointestinal function is so far unsettled even if it is indicated that epidural local aesthetic/opioid provide the most superior treatment.8,110

The effect of using epidurals on the postoperative pain outcome was investigated in two studies using visual analogue score (VAS).19,20 Improved postoperative pain relief is important for patient comfort and may decrease the hospital stay and lead to reduction in morbidity. Improved blood flow consequent on sympatholysis has additional potential benefits, including a reduction in thrombo-embolic complications.1

Some studies have shown that thoracic epidural analgesia with a mixture of local anaesthetics and opioids, in contrast with patient-controlled anaesthesia (PCA) IV opioids, provides superior pain relief and contributes to a faster restoration of bowel function.49,108 However, other trials with patients on a fast-track care pathway with intravenous PCA analgesia did not get further benefits with use of a pre-emptive thoracic epidural.111,114 In a Cochrane Database analysis,110 although epidural administration of local anaesthetics was found to accelerate gastrointestinal recovery and reduce nausea after abdominal surgery compared with epidural or systemic opioids, it did not reduce length of stay compared with patient-controlled opioid analgesia.83

And therefore, research continues to find the optimum infusion (constituents, concentration and total volume) and the optimum timing and duration of infusion to find significant difference between mid-thoracic epidural analgesia peri-operatively and PCA on the length of stay, too.

A practical problem may evolve during operations. The blockade of these fibres leads to hypotension and the laparotomy intensifies low blood pressure. Then it is very tempting to fill up with intravenous fluid to achieve normal tension. But, as we will discuss later, the risk is intravenous fluid overload. Therefore remember, peroperative hypotension is safely treated with vasopressors.


### **12. Preventing and treating postoperative nausea and vomiting**

Postoperative nausea and vomiting and postoperative ileus are well-recognized syndromes that lead to significant morbidity and prolong hospitalization. Anaesthesia is given worldwide to more than 75 million surgical patients annually. Untreated, one third of surgical patients suffer from PONV.115 Patients often rate PONV as worse than postoperative pain. Volatile anaesthetics, nitrous oxide and opioids appear to be the most important causes. Female gender, non-smoking and a history of motion sickness and PONV are the most important patient specific risk factors.116 Vomiting increases the risk of aspiration and has been associated with suture dehiscence, oesophageal rupture, subcutaneous emphysema, and bilateral pneumothorax. Numerous patho-physiological mechanisms are known to cause nausea or vomiting but their role for postoperative nausea and vomiting is not quite clear.

adverse consequences suggest that many high-risk patients undergoing major intra-abdominal surgery will receive substantial benefit from combined general and epidural anaesthesia intraoperatively with continuing postoperatively epidural analgesia.112,113 The effect of additional epidural opioid on gastrointestinal function is so far unsettled even if it is indicated that

The effect of using epidurals on the postoperative pain outcome was investigated in two studies using visual analogue score (VAS).19,20 Improved postoperative pain relief is important for patient comfort and may decrease the hospital stay and lead to reduction in morbidity. Improved blood flow consequent on sympatholysis has additional potential

Some studies have shown that thoracic epidural analgesia with a mixture of local anaesthetics and opioids, in contrast with patient-controlled anaesthesia (PCA) IV opioids, provides superior pain relief and contributes to a faster restoration of bowel function.49,108 However, other trials with patients on a fast-track care pathway with intravenous PCA analgesia did not get further benefits with use of a pre-emptive thoracic epidural.111,114 In a Cochrane Database analysis,110 although epidural administration of local anaesthetics was found to accelerate gastrointestinal recovery and reduce nausea after abdominal surgery compared with epidural or systemic opioids, it did not reduce length of stay compared with

And therefore, research continues to find the optimum infusion (constituents, concentration and total volume) and the optimum timing and duration of infusion to find significant difference between mid-thoracic epidural analgesia peri-operatively and PCA on the length

A practical problem may evolve during operations. The blockade of these fibres leads to hypotension and the laparotomy intensifies low blood pressure. Then it is very tempting to fill up with intravenous fluid to achieve normal tension. But, as we will discuss later, the risk is intravenous fluid overload. Therefore remember, peroperative hypotension is safely

 Mid-thoracic EDA during surgery and EDA or PCA postoperatively at least for 2-3 days, reduces PONV, postoperative ileus and pain and therefore reduces hospital stay

Postoperative nausea and vomiting and postoperative ileus are well-recognized syndromes that lead to significant morbidity and prolong hospitalization. Anaesthesia is given worldwide to more than 75 million surgical patients annually. Untreated, one third of surgical patients suffer from PONV.115 Patients often rate PONV as worse than postoperative pain. Volatile anaesthetics, nitrous oxide and opioids appear to be the most important causes. Female gender, non-smoking and a history of motion sickness and PONV are the most important patient specific risk factors.116 Vomiting increases the risk of aspiration and has been associated with suture dehiscence, oesophageal rupture, subcutaneous emphysema, and bilateral pneumothorax. Numerous patho-physiological mechanisms are known to cause nausea or vomiting but their role for postoperative nausea

Addition of opioid to epidural local anaesthetic provide superior analgesia

**12. Preventing and treating postoperative nausea and vomiting** 

epidural local aesthetic/opioid provide the most superior treatment.8,110

benefits, including a reduction in thrombo-embolic complications.1

patient-controlled opioid analgesia.83

of stay, too.

treated with vasopressors.

and vomiting is not quite clear.

Intra-operative and early postoperative supplemental oxygen may reduce nausea and vomiting after colonic surgery, and the effect may be as affective as odansetron.5

The use of short-acting volatile and intravenous anaesthetics can influence the postoperative course favourably and reduces the incidence of PONV markedly. At a moderate risk the use of total intravenous anaesthesia (TIVA) or an antiemetic is reasonable because PONV frequently delays discharge from post-anaesthesia care units. In very high-risk patients one may justify the combination of several prophylactic antiemetic interventions. The necessary doses are usually a quarter of those needed for treatment.116 Management techniques such as TIVA cannot be used once PONV is established. A reasonable treatment strategy in high risk patients would be to use dexamethasone and total intravenous anaesthesia as first- and second-line prophylaxis for postoperative nausea and vomiting, leaving serotonin antagonists as a rescue treatment.115 But dexamethasone, prevents PONV only when given in the beginning of surgery, probably due to reducing of surgery-induced inflammation. "Rescue" treatment, like serotonin antagonists, is ineffective when the same drug has already been used as prophylaxis. Prophylaxis may therefore be preferable to treatment of established PONV.


### **13. Surgical incisions**

To minimize the inflammatory process and pain, the incisions should be reduced to a minimum. Transverse incisions may cause less postoperative pain and better pulmonary function.117 Therefore laparoscopic incisions may be even better.118,119 Laparoscopic colon resections have showed advantages over conventional surgery. Blood loss is less; pain, treated with epidural or patient-controlled on demand analgesia, is less intense; time to return of bowel function is less, lung function is improved with reduced postoperative stay in hospital and improved quality of life in the first 30 days. The operation time is still longer with laparoscopic surgery than with conventional surgery. Re-operation is not more likely after laparoscopic surgery and general complications in the lungs, heart, urinary tract or deep vein thrombosis (DVT) were similar with the two surgery techniques. Wound infections were less in laparoscopic patients.120-123

Despite the minimally invasive nature of laparoscopy, host physiologic responses to stress are still variably activated. The sane gamut of metabolic, hormonal, inflammatory, and immune responses activated by open surgery are also induced by laparoscopy, but to a lesser degree and proportionate to the extent of surgical injury.124

Small incisions give smaller inflammatory responses. Laparoscopy even better.

### **14. Nasogastric intubation**

In 1933 Wangensteen and Paine125 wrote: "It is now twenty-four years since Westermann first used the duodenal tube in the relief of postoperative distension of peritonitis. With the introduction of the smooth tipped duodenal tube for nasal intubation by Levin in 1921 and satisfactory demonstration of the source of gas in postoperative dissention by McIver and his associates in 1926 as being largely swallowed air, the relief of postoperative distension through employment of the duodenal tube has become a matter of general practice." Thereafter the nasogastric tube was used routinely.

The practice was based largely on tradition and perception that nasogastric decompression protected patients from postoperative complications such as nausea, vomiting, aspiration, wound complications, anastomotic leak, and therefore allowed an earlier hospital discharge. Formerly, some used nasogastric tubes for 24 hours when using or more. Many of the early studies advocated nasogastric decompression allowing the patients ad libitum oral intake with the nasograstric tube in place, a practice that would not be advocated by most surgeons today.126

Routine nasogastric decompression was widely practiced after elective laparotomy. But the use of nasogastric tubes affect patients considerably. Studies have shown that nasogastric tube decompression does not shorten the duration of ileus and may, in some cases, contribute to postoperative complications such as nasal and pharyngeal injury, fever, atelectasis, increased gastric reflux, regurgitation, and pulmonary infections.82,127 RCTs could not show any relevant benefit. Although patients may develop abdominal distension or vomiting without nasogastric tube, this is not associated with an increase in complications or length of stay.126

The beginning of modifications in practice came after a RCT by Olesen et al 1984,128 which showed earlier passage of flatus without using tubes and no differences were found regarding duration of postoperative ileus, severity of postoperative paralysis, as measured by occurrence and duration of nausea and vomiting, postoperative per oral fluid intake, and time for defecation. And a meta-analysis showed that patients not having routine tube use had an earlier return of bowel function, a decrease in pulmonary complications and an insignificant trend toward increase in risk of wound infection. On the other hand routine use may decrease the risk of wound infection and subsequent ventral hernia.127 Although abdominal distension and vomiting are increased without nasogastric decompression, nasogastric tube insertion is required in only 5% to 7% of selectively treated patients,129 whereas nasogastric tube replacement postoperatively is required in 2% of routinely treated patients. Routine use of nasogastric decompression after elective operations is today not supported by the literature.127

Nasogastric tubes have no place routinely in elective surgery today

### **15. Preventing intra-operative hypothermia**

When compared with normothermic controls, the degree of mild hypothermia has been associated with a twofold to threefold increase in surgical wound infections.5

Maintenance of normothermia is critical for the surgical patient. Hypothermia has been shown to impair coagulation and increase the stress response and cardiovascular demands. Using forced-air warmer devices and providing adequate clothing and covering during surgery, can help to reduce postoperative wound infections, blood loss, untoward cardiac and overall rate of nitrogen excretion and catabolism.

Maintenance of normothermia reduces wound infections

his associates in 1926 as being largely swallowed air, the relief of postoperative distension through employment of the duodenal tube has become a matter of general practice."

The practice was based largely on tradition and perception that nasogastric decompression protected patients from postoperative complications such as nausea, vomiting, aspiration, wound complications, anastomotic leak, and therefore allowed an earlier hospital discharge. Formerly, some used nasogastric tubes for 24 hours when using or more. Many of the early studies advocated nasogastric decompression allowing the patients ad libitum oral intake with the nasograstric tube in place, a practice that would not be advocated by most surgeons

Routine nasogastric decompression was widely practiced after elective laparotomy. But the use of nasogastric tubes affect patients considerably. Studies have shown that nasogastric tube decompression does not shorten the duration of ileus and may, in some cases, contribute to postoperative complications such as nasal and pharyngeal injury, fever, atelectasis, increased gastric reflux, regurgitation, and pulmonary infections.82,127 RCTs could not show any relevant benefit. Although patients may develop abdominal distension or vomiting without nasogastric tube, this is not associated with an increase in

The beginning of modifications in practice came after a RCT by Olesen et al 1984,128 which showed earlier passage of flatus without using tubes and no differences were found regarding duration of postoperative ileus, severity of postoperative paralysis, as measured by occurrence and duration of nausea and vomiting, postoperative per oral fluid intake, and time for defecation. And a meta-analysis showed that patients not having routine tube use had an earlier return of bowel function, a decrease in pulmonary complications and an insignificant trend toward increase in risk of wound infection. On the other hand routine use may decrease the risk of wound infection and subsequent ventral hernia.127 Although abdominal distension and vomiting are increased without nasogastric decompression, nasogastric tube insertion is required in only 5% to 7% of selectively treated patients,129 whereas nasogastric tube replacement postoperatively is required in 2% of routinely treated patients. Routine use of nasogastric decompression after elective operations is today not

When compared with normothermic controls, the degree of mild hypothermia has been

Maintenance of normothermia is critical for the surgical patient. Hypothermia has been shown to impair coagulation and increase the stress response and cardiovascular demands. Using forced-air warmer devices and providing adequate clothing and covering during surgery, can help to reduce postoperative wound infections, blood loss, untoward cardiac

Nasogastric tubes have no place routinely in elective surgery today

associated with a twofold to threefold increase in surgical wound infections.5

**15. Preventing intra-operative hypothermia** 

and overall rate of nitrogen excretion and catabolism.

Maintenance of normothermia reduces wound infections

Thereafter the nasogastric tube was used routinely.

today.126

complications or length of stay.126

supported by the literature.127

### **16. Peri-operative fluid management**

Intravenous fluid and electrolytes are given to resuscitate the patient from losses sustained during surgery and to maintain homeostasis during periods when oral intake may not be possible. In major surgery, the need for intravenous fluid is greater. However, the optimum fluid replacement strategy remains controversial.

Avoidance of intravenous fluid overloading is an important element in many protocols. Current practice in fluid regimens has been based on 40-year old concepts.130 It was postulated a decrease in functional extracellular fluid after surgery but this decrease has never been found.27,131

However, a study on dogs back in 1937, showed that a modest positive salt and water balance caused weight gain after elective colonic surgery and was associated with delayed recovery and gastrointestinal motility, increased complication rate and hospital stay.132 The same was found in humans in 2002.133 An excess of salt and water may lead to more complications than restriction of fluid.

Francis Moore first recommended restriction in fluid regimen.134 He argued that the metabolic-endocrine response to trauma, (conservation of salt and water), required a fluid restriction. Shires' recommendations have led to 4-6 litres or more intravenous substitution during surgery and 24 hours after, despite minimal blood loss. In contrast, "dry" regimen has been considered beneficial in thoracic surgery.135 Intravenous fluid overload or excess early sodium and fluid prescription during and after surgery have been shown to give adverse outcome like decrease in muscular oxygen tension and delayed recovery of gastrointestinal function after segmental colonic resection with moderate fluid restriction. Postoperative weight gains after intra-operative fluid overload have been associated with poor survival and complication.27,136,137 The pattern peri-operative intravenous fluid administration has a major effect upon cardio-respiratory and anastomotic complications, and restricted peri-operative intravenous fluid management and a preoperative carbohydrate drink were found to be of specific importance for beneficial outcomes.32

Factors that allow successful use of restricted intra-operative fluid regimen include preventing the patient from coming to the theatre in a dehydrated state by avoiding bowel preparation or excessive duration of preoperative fasting. There was no apparent difference between the effects of fluid-restricted and standard or liberal fluid regimens on outcome in patients undergoing elective open abdominal surgery in a meta-analysis. However, patients managed in a state of fluid balance fared better than those managed in a state of fluid imbalance.50,138 It is clear that restriction of intravenous fluid during and after operation is safe in well-hydrated patients undergoing major elective abdominal surgery50 without finding any significant effect on postoperative gastrointestinal function or hospital stay between conservative intra-operative fluid control, and postoperative restriction of fluids and sodium. On the other hand, restricted postoperative IV fluid management, as performed in one trial, in patients undergoing major abdominal surgery, appears harmful as it is accompanied by an increased risk of major postoperative complications and a prolonged postoperative hospital stay.139 But this study was not an ERAS protocol and had no multimodal approximation.

Some studies have used Doppler-guided fluid administration as goal-directed therapy. Oesophageal Doppler-guided fluid management may improve outcome following major intra-abdominal surgery. However, comparison with fluid restriction strategies, including a cost-effectiveness analysis is required.139 Evidence regarding use of Doppler-guided fluid administration is limited by heterogeneity in trial design, and recent advances in surgical techniques and peri-operative care may largely offset the initial clinical benefits observed.140

All together when using standardized definitions, restricted rather than standard fluid amount according to current textbook opinion, and goal-directed fluid therapy rather than fluid therapy guided by conventional hemodynamic variables, reduce morbidity after colorectal resection.141


### **17. Drainage of peritoneal cavity following colonic anastomosis**

Drainage of chest empyema and ascites go back to the Hippocratic era. Ambroise Pare was the first to describe drainage of the abdominal cavity, but abdominal drainage had probably been used in practice earlier.142 During the last 2 centuries, surgeons also used drains for prophylactic purposes. Prophylactic drains have been employed to remove intra-peritoneal collections such as ascites, blood, bile, chyle, and pancreatic or intestinal juice.143 Another assumed potential function of prophylactic drains is their signal function to detect early complications, such as postoperative haemorrhage and leakage of enteric suture lines.

F. Manley Sims144 was the first surgeon who used prophylactic drains after gynaecological operations in the end of 19th century. Since that time, surgeons have routinely used prophylactic drainage of the peritoneal cavity after abdominal surgery.143 Many surgeons use prophylactic drainage after colorectal anastomoses worldwide to prevent anastomotic dehiscence by evacuating fluid collections. Previous authors have suggested that drainage is important to prevent accumulation of exudative fluid, but randomised trials that examined pelvic fluid accumulation in the presence and absence of a drain demonstrated no reduction in fluid accumulation despite the presence of a functioning drain.145,146 And there is no evidence that fluid exuded from the pre-sacral fascia will remain in the pelvis rather than communicate with the free peritoneal cavity, and may therefore not be susceptible to capture by a pelvic drain. In addition, a drain will usually not serve to control an anastomotic leak as many surgeons expect. The fact is that only in very few instances leaks among drained patients in evaluated studies, pus or faeces emerging from the drain.146,147

These traditional practices can impede mobility and cause discomfort and thereof increased morbidity. The use should be selective and not used routinely. Many surgeons continue to place a prophylactic drain in the pelvis after completion of a colorectal anastomosis, despite considerable evidence that this practice may not be useful. If drainage tubes first have been inserted they are normally left in situ for several days until drainage ceases. During the last 3 decades, surgeons have made effort to investigate the value of prophylactic drainage after abdominal surgery in controlled randomised clinical trials. Despite evidence-based data questioning prophylactic drainage in many instances, most surgeons around the world continue to use them on a routine bases. A possible reason for the persistence of practice may be that the surgeons are not convinced by the negative results of the existing trials. The

Some studies have used Doppler-guided fluid administration as goal-directed therapy. Oesophageal Doppler-guided fluid management may improve outcome following major intra-abdominal surgery. However, comparison with fluid restriction strategies, including a cost-effectiveness analysis is required.139 Evidence regarding use of Doppler-guided fluid administration is limited by heterogeneity in trial design, and recent advances in surgical techniques and peri-operative care may largely offset the initial clinical benefits observed.140 All together when using standardized definitions, restricted rather than standard fluid amount according to current textbook opinion, and goal-directed fluid therapy rather than fluid therapy guided by conventional hemodynamic variables, reduce morbidity after

Avoiding unnecessary bowel preparation or excessive duration of preoperative fasting

Drainage of chest empyema and ascites go back to the Hippocratic era. Ambroise Pare was the first to describe drainage of the abdominal cavity, but abdominal drainage had probably been used in practice earlier.142 During the last 2 centuries, surgeons also used drains for prophylactic purposes. Prophylactic drains have been employed to remove intra-peritoneal collections such as ascites, blood, bile, chyle, and pancreatic or intestinal juice.143 Another assumed potential function of prophylactic drains is their signal function to detect early complications, such as postoperative haemorrhage and leakage of enteric suture lines.

F. Manley Sims144 was the first surgeon who used prophylactic drains after gynaecological operations in the end of 19th century. Since that time, surgeons have routinely used prophylactic drainage of the peritoneal cavity after abdominal surgery.143 Many surgeons use prophylactic drainage after colorectal anastomoses worldwide to prevent anastomotic dehiscence by evacuating fluid collections. Previous authors have suggested that drainage is important to prevent accumulation of exudative fluid, but randomised trials that examined pelvic fluid accumulation in the presence and absence of a drain demonstrated no reduction in fluid accumulation despite the presence of a functioning drain.145,146 And there is no evidence that fluid exuded from the pre-sacral fascia will remain in the pelvis rather than communicate with the free peritoneal cavity, and may therefore not be susceptible to capture by a pelvic drain. In addition, a drain will usually not serve to control an anastomotic leak as many surgeons expect. The fact is that only in very few instances leaks among drained patients in evaluated studies, pus or faeces emerging from the drain.146,147

These traditional practices can impede mobility and cause discomfort and thereof increased morbidity. The use should be selective and not used routinely. Many surgeons continue to place a prophylactic drain in the pelvis after completion of a colorectal anastomosis, despite considerable evidence that this practice may not be useful. If drainage tubes first have been inserted they are normally left in situ for several days until drainage ceases. During the last 3 decades, surgeons have made effort to investigate the value of prophylactic drainage after abdominal surgery in controlled randomised clinical trials. Despite evidence-based data questioning prophylactic drainage in many instances, most surgeons around the world continue to use them on a routine bases. A possible reason for the persistence of practice may be that the surgeons are not convinced by the negative results of the existing trials. The

Restricted, goal-directed fluid therapy seems to be the best regimen

**17. Drainage of peritoneal cavity following colonic anastomosis** 

colorectal resection.141

relatively small sample size and the rarity of the outcomes in these studies limit their power to exclude a true benefit, should one exist.142

The large variability of drainage duration may indicate the need for future RCT focused on drainage duration, especially on short-term drainage (24-48 hours). But reviews and metaanalysis of the literature found no evidence that justifies routine drainage of colon and rectal anastomosis after uncomplicated surgery today.143,147 They showed no difference in all outcome measures (mortality, clinical anastomotic dehiscence, radiological anastomotic dehiscence, wound infection, reoperation, length of hospital stay, extra-abdominal complications).145,148

However, due to the lack of statistical power after stratification to the level of the anastomosis, anastomosis in the pelvic still may need short-time drainage. Especially concerning the increase in the rate of neoadjuvant radiotherapy and the increase of Gy used, the reactive hyperaemia should indicate the need of drainage.


### **18. Urinary drainage**

Some prefer to leave the catheter in situ for several days after surgery, until the patient is fully mobilized. Others remove it the day after surgery on colonic resections, leaving the catheter for seven days after pelvic surgery. Few RCTs are available to define the optimal duration of such drainage, but patients require a shorter period of urinary catheterisation, are able to mobilise more quickly, and had an earlier return of gut function in optimized pathways.5,20 One study recommend in major low-rectal operations, urinary bladder drainage to be limited to about 3 days and to 1 day after types of colonic surgery.5

1 day after colonic surgery, about 3 days after low-rectal operation

### **19. Prevention of postoperative ileus**

The aetiology of postoperative ileus is complex, and major intrinsic contributing factors include surgical stress (i.e., from physical manipulation of the bowel), secretion of inflammatory mediators and endogenous opioids in the gastrointestinal tract, and changes in hormone levels and electrolyte and fluid balance, pharmacological agents such as inhalation anaesthetics, and use of opioids for postoperative analgesia implying that both stimulation of nociceptive afferent and sympathetic efferent nerve pathway initiate ileus.82,108,113 Opioids are the most widely prescribed analgesics used to treat postoperative pain. However, opioids bind to µ-opioid receptors within the gut, exacerbating postoperative ileus.83 The µ-opioid receptors have been the subject of investigative targets to block and thereby add a pharmacologic adjunct that has previously been lacking.149

Postoperative ileus is defined as a disruption of the normal peristaltic motion of the gut, resulting in failure to propel intestinal content through the gastrointestinal tract. Symptoms associated with postoperative ileus include abdominal distension and bloating, nausea and/or vomiting, lack of bowel sounds, gas and fluid accumulation in the bowel, delayed passage of flatus and stool, and inability to tolerate solid diet. Small bowel ileus resolves within hours of manipulation, but gastric and colonic motor function does not return until 48 to 72 hours postoperatively.23 It is due to inhibition of extrinsic motility regulation in the colon. The potential benefits from prompt resolution of postoperative ileus may include reduction in the incidence of bowel complications, the potential for more rapid return to normal bowel function, improved patient comfort, reduced length of stay, and reduced healthcare costs.82

Postoperative ileus has been shown reduced in fast-track groups47 even though Lewis67 found an increased risk of vomiting among patients fed early. This meta-analysis did not include patients in an ERAS protocol. And again, including many ERAS elements in a clinical pathway may result in a cumulative effect not found studying one at the time.

The greatest advance in limiting postoperative ileus to date has probably resulted from the expanded use of laparoscopic surgery and the advantage of limiting tissue trauma. Animal and clinical trials have demonstrated significant reductions in postoperative ileus after laparoscopic colectomy compared with open techniques, which translate into decreased hospital stay.149

Postoperative ileus is one of the most common causes of prolonged length of hospital stay. Furthermore, postoperative ileus may be a significant contributing factor for hospital readmission.

 Opioids exacerbating postoperative ileus, but the aetiology is very complex and many elements may contribute

### **20. Postoperative nutritional care**

Standard before ERAS was no oral alimentation until flatus passed, and then progressive diet was initiated. Initially, clear fluids were given, followed by full liquids, and than a regular diet. On average, fluids were commenced on the third or fourth day, with discharge of the patient on the seventh or the eighth day following surgery. Intravenous fluid was administered until the patient was able to drink ad libitum. Until intestinal activity was demonstrated to have reasserted itself in a normal way, by the detection of vigorous peristaltic sounds on regular auscultation of the abdomen and the passage of flatus per rectum, normal diet was banned.

The immediate advantage of caloric intake could be a faster recovery with fewer complications. In the 1990s, early oral intake after elective abdominal colorectal surgery was found safe and was tolerated by the majority of the patients, though they were on a clear liquid diet on the first postoperative day, and advanced to a regular diet within the next 24- 72 hours,150,151 and there was a significant attenuation in gut mucosal permeability.152 Early studies showed early feeding as a key factor in reducing acute hospital stay,153,154 and later studies reduced infection rate and the length of stay, but did not significantly reduce mortality.1 A recent meta-analyse by Lewis et al155 concluded with reduced mortality, but increased vomiting. However, the trend was in the direction of reduced complication rate and hospital stay. There is no advantage keeping the patient "nil by mouth".

Reduction in complication rates may explain the shortened length of stay as might faster return of gastrointestinal function upon early commencement of enteral feeding.78 Early

within hours of manipulation, but gastric and colonic motor function does not return until 48 to 72 hours postoperatively.23 It is due to inhibition of extrinsic motility regulation in the colon. The potential benefits from prompt resolution of postoperative ileus may include reduction in the incidence of bowel complications, the potential for more rapid return to normal bowel function, improved patient comfort, reduced length of stay, and reduced

Postoperative ileus has been shown reduced in fast-track groups47 even though Lewis67 found an increased risk of vomiting among patients fed early. This meta-analysis did not include patients in an ERAS protocol. And again, including many ERAS elements in a clinical pathway may result in a cumulative effect not found studying one at the time.

The greatest advance in limiting postoperative ileus to date has probably resulted from the expanded use of laparoscopic surgery and the advantage of limiting tissue trauma. Animal and clinical trials have demonstrated significant reductions in postoperative ileus after laparoscopic colectomy compared with open techniques, which translate into decreased

Postoperative ileus is one of the most common causes of prolonged length of hospital stay. Furthermore, postoperative ileus may be a significant contributing factor for hospital

Opioids exacerbating postoperative ileus, but the aetiology is very complex and many

Standard before ERAS was no oral alimentation until flatus passed, and then progressive diet was initiated. Initially, clear fluids were given, followed by full liquids, and than a regular diet. On average, fluids were commenced on the third or fourth day, with discharge of the patient on the seventh or the eighth day following surgery. Intravenous fluid was administered until the patient was able to drink ad libitum. Until intestinal activity was demonstrated to have reasserted itself in a normal way, by the detection of vigorous peristaltic sounds on regular auscultation of the abdomen and the passage of flatus per

The immediate advantage of caloric intake could be a faster recovery with fewer complications. In the 1990s, early oral intake after elective abdominal colorectal surgery was found safe and was tolerated by the majority of the patients, though they were on a clear liquid diet on the first postoperative day, and advanced to a regular diet within the next 24- 72 hours,150,151 and there was a significant attenuation in gut mucosal permeability.152 Early studies showed early feeding as a key factor in reducing acute hospital stay,153,154 and later studies reduced infection rate and the length of stay, but did not significantly reduce mortality.1 A recent meta-analyse by Lewis et al155 concluded with reduced mortality, but increased vomiting. However, the trend was in the direction of reduced complication rate

Reduction in complication rates may explain the shortened length of stay as might faster return of gastrointestinal function upon early commencement of enteral feeding.78 Early

and hospital stay. There is no advantage keeping the patient "nil by mouth".

healthcare costs.82

hospital stay.149

readmission.

elements may contribute

rectum, normal diet was banned.

**20. Postoperative nutritional care** 

enteral feeding is predicated on radiologic and electro-physiologic studies that indicate a return of small bowel function in 4 to 8 hours post incision, right colon function by 24 hours and left colon function by 72 hours. Severity in duration of the atony can be attenuated by laparoscopy, reduction in opioid-based anaesthesia and analgesia, as well as blockade of the sympathetic reflex circuit through effective continuous thoracic EDA with local anaesthetics.

Early oral intake has become a routine feature in management after elective colonic surgery. And when is it appropriate to start? Patients should be encouraged to commence oral fluid intake 4 hours after surgery.8


### **21. Early mobilization**

Previously, active movements were encouraged in bed after surgery. On the second or the third evening, the patient was usually helped out of bed for a few minutes whilst the bed was made. Thereafter the ambulation was gradually increased.

However, immobilization, over a longer period, can lead to organ dysfunction, loss of lean body mass, reduced muscle power and fatigue.20 Bed rest not only increases insulin resistance but also decreases pulmonary function and tissue oxygenation and give an increased risk of thromboembolism.8 To avoid pulmonary complications caused by reduced pulmonary function due to immobilization and reduced tissue oxygenation, mobilizing the patients as soon as possible is important. Mobilization starts on the day of surgery or on the first operative day.107

Patients should be nursed in an environment that encourage independence and mobilization. A care plan that facilitates patients being out of bed for up to 2 hours on the day of surgery and 6 hours thereafter is recommended.

To be considered fit for discharge patients had to be apyrexial, fully mobile, passing flatus or faeces, and using oral analgesics only for pain control.50

Out of bed the operation day and 6 hours first operation day and thereafter

### **22. Economic consideration**

In colorectal surgery, cost-analysis of enhanced recovery protocols is limited. Two early clinical pathway programmes proved useful in standardising patient care and reducing costs,11,48 and were probably instrumental in the development of modern ERAS protocols.156 None of these studies addressed the set-up costs of an ERAS protocol nor provided a detailed breakdown of where cost savings were achieved in the postoperative recovery phase. However, there has been a huge paradigm shift in postoperative care principles in colorectal surgery since that time, making the cost-analysis reported in those studies inapplicable to current programmes.

Cost-effective analysis has shown that an ERAS programme is a very cost-effective intervention in elective colonic surgery in the setting of an elective hospital.156 Another casecontrol study by King et al 2006157 focussing on quality-of-life after colonic and rectal surgery, showed in hospital stay half as long as those receiving conventional care, with no increased morbidity, deterioration in quality of life or increased cost.

Evidence from the literature, supports the view that the ERAS pathway seems to reduce the overall healthcare cost.114,158,159 The largest reduction was in expenses for nursing care, although significant reduction were recorded also in costs of laboratory tests, medications (pharmacy), medical service and other expenses.114 From a health economics point of view, the data suggests that, with the decrease of complications and hospital stay and similar readmission rates, the cost of treatment per patient would be significant lower for those treated with an ERAS pathway than those receiving traditional care, despite the need for dedicated staff to implement the pathway.33

### **23. Implementation**

Improved adherence to the standardized multimodal ERAS protocol is significantly associated with improved clinical outcomes following major colorectal cancer surgery, indicating a dose-response relationship.32 In spite of a large evidence base for peri-operative care aiming to alleviate postoperative catabolism and organ dysfunction, surgical patients remain exposed to unnecessary starvation, suboptimal stress reduction, and fluid overload.160

Although the concept of multimodal postoperative rehabilitation seems rationale and simple, implementation in daily practice has been surprisingly slow so far. This can be partly explained by the need to break with longstanding traditions such as preoperative fasting, postoperative advancement of oral feeding and delayed mobilization.47 Partly that the ERAS concept as such possibly appears elusive because the relative contribution of each intervention in the program remains uncertain. The most plausible explanation is that a successful multimodal rehabilitation program requires the reorganisation of peri-operative care, with increased collaboration between the patient, anaesthetist (acute pain service), surgical nurse and surgeon. Furthermore, major efforts must be made for educational programmes, with emphasis on peri-operative patho-physiology, as well as a revision of traditional postoperative care programmes with drains, gastrointestinal tubes, catheters, restrictions etc.48

The step from best evidence to best practice is simple. However, most of the time it is not, and we need various strategies targeting obstacles to change at different levels, which could even present conflicting values for individual practitioners. Therefore, changes in clinical practice are only partly within doctor's control. Obstacles to change are generally not only in the professional setting but also in the patient, the organisation of care processes, resources, leadership, or the political environment. The prevailing professional and organisational culture towards quality determines the outcome to a large extent.161

For instance, patients were not expecting to go home in less than seven days and surgeons were cautious with early discharge.108 Patients made an early functional recovery, but discharge was generally 2 days later.9 Strict discharge criteria were met approximately 1,5 days before actual discharge. Social factors, patient's needs, and physician care all influenced the actual discharge date or length of stay.107

control study by King et al 2006157 focussing on quality-of-life after colonic and rectal surgery, showed in hospital stay half as long as those receiving conventional care, with no

Evidence from the literature, supports the view that the ERAS pathway seems to reduce the overall healthcare cost.114,158,159 The largest reduction was in expenses for nursing care, although significant reduction were recorded also in costs of laboratory tests, medications (pharmacy), medical service and other expenses.114 From a health economics point of view, the data suggests that, with the decrease of complications and hospital stay and similar readmission rates, the cost of treatment per patient would be significant lower for those treated with an ERAS pathway than those receiving traditional care, despite the need for

Improved adherence to the standardized multimodal ERAS protocol is significantly associated with improved clinical outcomes following major colorectal cancer surgery, indicating a dose-response relationship.32 In spite of a large evidence base for peri-operative care aiming to alleviate postoperative catabolism and organ dysfunction, surgical patients remain exposed to unnecessary starvation, suboptimal stress reduction, and fluid

Although the concept of multimodal postoperative rehabilitation seems rationale and simple, implementation in daily practice has been surprisingly slow so far. This can be partly explained by the need to break with longstanding traditions such as preoperative fasting, postoperative advancement of oral feeding and delayed mobilization.47 Partly that the ERAS concept as such possibly appears elusive because the relative contribution of each intervention in the program remains uncertain. The most plausible explanation is that a successful multimodal rehabilitation program requires the reorganisation of peri-operative care, with increased collaboration between the patient, anaesthetist (acute pain service), surgical nurse and surgeon. Furthermore, major efforts must be made for educational programmes, with emphasis on peri-operative patho-physiology, as well as a revision of traditional postoperative care programmes with drains, gastrointestinal tubes, catheters,

The step from best evidence to best practice is simple. However, most of the time it is not, and we need various strategies targeting obstacles to change at different levels, which could even present conflicting values for individual practitioners. Therefore, changes in clinical practice are only partly within doctor's control. Obstacles to change are generally not only in the professional setting but also in the patient, the organisation of care processes, resources, leadership, or the political environment. The prevailing professional and organisational

For instance, patients were not expecting to go home in less than seven days and surgeons were cautious with early discharge.108 Patients made an early functional recovery, but discharge was generally 2 days later.9 Strict discharge criteria were met approximately 1,5 days before actual discharge. Social factors, patient's needs, and physician care all

culture towards quality determines the outcome to a large extent.161

influenced the actual discharge date or length of stay.107

increased morbidity, deterioration in quality of life or increased cost.

dedicated staff to implement the pathway.33

**23. Implementation** 

overload.160

restrictions etc.48

Introducing ERAS protocols usually requires a major shift in clinical routines, and many units may have difficulties in making all these changes at once. The delay in integrating novel management strategies with routine practice may be ascribed to the time required to develop guidelines, the implementation process, the target group of professionals, the patients, the cultural and social setting, and the organizational and economic environment.9 Much may be achieved simply by raising the quality of surgical care according to existing evidence. In many ways, this is far more difficult task than simply doing more research.4

Nevertheless, some of the elements in the ERAS program, such as omission of routine bowel preparation for colonic resections, no routine use of postoperative drains, early removal of nasogastric tubes, and early feeding and mobilization, have already been incorporated in traditional care. The effect of the different peri-operative ERAS interventions as well as the importance of adherence to the protocol in terms of clinical outcomes, such as postoperative symptoms, morbidity, and length of stay (LOS), remain unclear.32

If you would like to start tomorrow to change practice and implement evidence, prepare well: involve the relevant people; develop a proposal for change that is evidence based, feasible, and attractive; study the main difficulties in achieving the change, and select a set of strategies and measures at different levels linked to that problem; of course, within your budget and possibilities. Define indicators for measurement of success and monitor progress continuously or at regular intervals. And, finally, enjoy working on making patients' care more effective, efficient, safe, and friendly.161

### **24. References**


[12] Bardram L, Funch-Jensen P, Jensen P et al: Recovery after laparoscopic colonic surgery

[13] Basse L, Jakobsen DH, Billesbølle P et al: A Clinical Pathway to Accelerate Recovery

[14] Kiran RP, Delaney CP, Senagore AJ et al: Outcomes and prediction of hospital readmission after intestinal surgery. J Am Coll Surg. 2004 Jun;198(6):877-83. [15] Kehlet H & Mogensen T: Hospital Stay of 2 days after open sigmoidectomy with a

[16] Hensel M, Scwenk W, Bloch A et al: The role of anaesthesiology in fast track concepts in

[17] Basse L, Thorbøl JE, Løssl K et al: Colonic Surgery with Accelerated Rehabilitation or

[18] Jakobsen DH, Sonne E, Andreasen J, Kehlet H: Convalescence after colonic surgery with

[19] Anderson ADG, McNaught CE, MacFie J et al: Randomized clinical trial of multimodal

[20] Gatt M, Anderson ADG, Reddy BS et al: Randomized clinical trial of multimodal

[21] Nygren J, Hausel J, Kehlet H et al: A comparison in five European Centres of case mix,

[23] Behrns KE, Kircher AP, Galanko JA, Brownstein MR, Koruda MJ. Prospective

[25] Schwenk W, Neudecker J, Raue W et al: "Fast-track" rehabilitation after rectal cancer

[26] Teeuwen PHE, Bleichrot RP, Strik C et al: Enhanced Recovery after Surgery (ERAS)

[27] Khoo CK, Vickery CJ, Forsyth N et al: Aprospective Randomized Controlled Trial of

[28] Muller S, Zalunardo MP,Hubner M et al: A fast-track program reduces complications

Colorectal Resection for Cancer. Ann Surg 2007, 245(6):867-72.

following elective intestinal surgery. J Gastrointest Surg 2000;4:217–21. [24] Delaney CP, Fazio VW, Senagore AJ et al: "Fast track" postoperative management

pelvic colorectal surgery. Br J Surg 2001; 88: 1533-8.

resection Int J Colorectal Dis. 2006 Sep;21(6):547-53.

perioperative care in colorectal surgery Clin Nutr (2005) 24, 455–461 [22] Delaney CP, Zutshi M, Senagore AJ et al: Prospective, randomized, controlled trial

optimization and standard perioperative surgical care. Br J Surg 2003; 90: 1497–

optimization of surgical care in patients undergoing major colonic resection. Br J

clinical management and outcomes following either conventional or fast-track

between a pathway of controlled rehabilitation with early ambulation and diet and traditional postoperative care after laparotomy and intestinal resection. Dis Colon

randomized trial of early initiation and hospital discharge on a liquid diet

protocol for patients with high co-morbidity undergoing complex abdominal and

Versus Conventional Postoperative Care in Colorectal Surgery. J Gastrointest Surg

Multimodal Perioperative Mangaement Protocol in Patients Undergoing Elective

and length of hospital stay after open colonic surgery. Gastroenterology 2009;136:

multimodal rehabilitation programme. Br J Surg 1999; 86: 227-30.

after Colonic Resection. Ann Surg 2000; 232(1):51–57

colonic surgery. Anaesthesist 2006; 55(1): 80-92.

Conventional Care. Dis Colon Rectum 2004; 47: 271–278

fast-track vs conventional care. Color Dis 2006; 8 (10), 683–687.

Mar 25 (345): 763.

1504.

Surg 2005; 92: 1354–62.

Rectum. 2003 Jul;46(7):851-9.

2010; 14: 88-95.

842-7

with epidural analgesia, and early oral nutrition and mobilisation. Lancet 1995;


[47] Wind J, Polle SW, Fung Kon JinPHP et al: Systematic review of enhanced recovery

[48] Pritts TA, Nussbaum MS, Flesh LV et al: Implementation of a Clinical Pathway

[49] Kehlet H & Holte K: Effect of postoperative analgesia on surgical outcome Br. J.

[50] MacKay G, Fearon K, McConnachie A et al: Randomized clinical trial of the effect of

[51] Ramirex JM, Blasco JA, Roig JV et al: Enhanced recovery in colorectal surgery: a

[52] Halsted WS. Circular suture of the intestine: an experimental study. Am J Med Sci 1887;

[53] Hughes ESR: Asepsis in large-bowel surgery. Ann Roy Coll Surg Engl 1972; Vol 51: 347-

[54] Irving AD & Scrimgeour D: Mechanical bowel preparation for colonic resection and

[55] Burke P, Mealy K, Gillen P et al: Requirement for bowel preparation in colorectal

[56] Platell C & Hall J: What is the role of bowel preparation in patients undergoing

[57] Contant CME, Hop WCJ, Van´t Sant HP et al: Mechanical bowel preparation for elective colorectal surgery: a multicenter randomised trial. Lancet 2007; 370: 2112-7. [58] Jung B, Pahlman L, Nystrom PO et al for the Mechanical Bowel Preparation Study

[59] Slim K, Vicaut E, Panis Y et al: Meta-analysis of randomised clinical trials of colorectal surgery with or without mechanical bowel preparation. Br J Surg 204; 91: 1125-30. [60] Guenaga KF, Matos D, Castro AA et al: Mechanical bowel preparation for elective

[61] Guenaga KK, Matos D, & Wille-Jorgensen P: Mechanical bowel preperation for elective colorectal surgery. Cochrane Database Syst Rev 2011; (1):CD001544. [62] Lichtenstein G: Bowel preparations for colonoscopy: a review. Am J Health Syst Pharm.

[63] Hoy SM, Scott LJ & Wagstaff AJ: Sodium picosulfate/magnesium citrate: a review of its

[64] Belsey J, Epstein O & Heresbach D: Systematic review: adverse event reports for oral

[65] Dykes C & Cash BD: Key safety issues of bowel preparations for colonoscopy and

[66] Wexner SD, Beck DE, Baron TH et al: A consensus document on bowel preparation

sodium phosphate and polyethylene glycol. Aliment Pharmacol Ther. 2009

importance of adequate hydration. Gastroenterol Nurs. 2008 Jan-Feb; 31(1):30-5;

before colonoscopy: prepared by a Task Force from the American Socisty of Colon and Rectal Surgeons (ASCRS), the American Societu for Gastrointestinal

colorectal surgery. Cochrane database Syst rev 2005; 1: CD001544.

Group. Multicentre randomized clinical trial of mechanical bowel preparation in

colorectal surgery? Dis Colon Rectum 1998; Vol42: 875-82.

elective colonic surgery. Br J Surg 2007; 94: 689-95.

use as a colorectal cleanser. Drugs. 2009; 69(1):123-36.

Decreases Length of Stay and Cost for Bowel Resection. Ann Surg 1999; 230(5): 728-

postoperative intravenous fluid restriction on recovery after elective colorectal

programmes in colonic surgery. Br J Surg 2006; 93: 800–809

Anaesth., July 1, 2001; 87(1): 62 - 72.

surgery. Br J Surg 2006; 93: 1469–74.

multicentre study. BMC Surgery 2011;11:1-8.

anastomosis. Br J Surg 1987; Jul 74(7): 580-1.

surgery. Br J Surg 1994; Jun 81(6): 907-10.

2009 Jan 1; 66(1):27-37.

Jan;29(1):15-28.

quiz 36-7.

33.

94: 436-61.

56.

Endoscopy (ASGE), and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES). Surh Endosc 2006; Vol 20(7): 1161.


[86] Fukami Y, Terasaki M, Okamoto Y et al: Efficacy of preoperative dexamethasone in

[88] Zargar-Shostari K, Sammour T, Kahokehr A et al: Randomised clinical trial of the effect

[89] O'Donnell M & Weitz JI: Thromboprophylaxis in surgical patients. Can J Surg 2003; Vol

[90] Bergqvist D: Low molecular weight heparin for the prevention of venous thromboembolism after abdominal surgery. Br J Surg 2004; 91: 965-74. [91] Leonardi MJ, McGory ML & Ko CY: A Systematic Review of Deep Venous Thrombosis

[92] Geerts WH, Bergqvist D, Pineo GF et al: : Prevention of Venous Thromboembolism:

[93] Mohn AC, Egge J, Røkke O: Low Risk of Thromboembolic Complications after Fast-

[94] Rasmussen MS, Jorgensen LN, Wille-Jorgensen P et al: Prolonged prophylaxis with

[95] Kakkar VV, Cohen AT, Edmonson RA: Low molecular weight versus standard heparin

review and meta-analysis. Thromb Haemost. 2005 Feb; 93(2):236-41. [98] ENOXACAN Study Group: Efficacy and safety of enoxaparin versus unfractionated

Stay. Gastroenterology Research Vol. 4, No. 3, Jun 2011.

Feb;74(2):160-7.

46(2): 129-35.

2007; Vol 14(2): 929-936.

Haemost 2006; 4: 2384–2390.

1997; 84(8):1099-1103.

Database Syst Rev 2009; Issue 1: CD004318.

cancer. NEJM 2002; 346: 975-80.

colectomy. Br J Surg 2009; 96: 1253-61.

(8th edition). Chest 2008; 133; 381-453.

patients with laparoscopic cholecystectomy: a prospective randomized doubleblind study. J Hepatobiliary Pancreat Surg. 2009;16(3):367-71. Epub 2009 Mar 31. [87] Kirdak T, Yilmazlar A, Cavun S et al: Does single, low-dose preoperative

dexamethasone improve outcomes after colorectal surgery based on an enhanced recovery protocol? Double-blind, randomized clinical trial. Am Surg. 2008

of glucocorticoids on peripheral inflammation and postoperative recovery after

Prophylaxis in Cancer Patients: Implications for Improving Quality. Ann Surg Onc

American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

Track Abdominal Surgery With Thrombosis-Prophylaxis Only During Hospital

dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open-label study. Thromb

for prevention of venous thromboembolism after major abdominal surgery. The Thromboprophylaxis Collaborative Group. Lancet. 1993 Jan 30;341(8840):259-65. [96] Vaitkus PT, Leizorovicz A, Cohen AT: Mortality rates and risk factors for asymptomatic deep vein thrombosis in medical patients. Thromb Haemost. 2005 Jan;93(1):76-9. [97] Wille-Jørgensen P, Jorgensen LN, Crawford M: Asymptomatic postoperative deep vein

thrombosis and the development of postthrombotic syndrome. A systematic

heparin for prevention of deep vein thrombosis in elective cancer surgery: a double-blind randomized multicentre trial with venographic assessment. Br J Surg

Low Molecular Weight heparin for abdominal or pelvic surgery. Cochrane

prophylaxis against venous thromboembolism with enoxaparin after surgery for

[99] Rasmussen MS, Jørgensen LN, Wille-Jørgensen P: Prolonged thromboprophylaxis with

[100] Bergqvist D, Agnelli G, Cohen AT et al: The ENOXACAN II investigators: Duration of


[117] Lindgren PG, Nordgren SR, Oresland T et al: Midline or transverse abdominal incision for right-sided colon cancer: a randimized trial. Colorectal Dis 2001; 3:46-50. [118] Reza MM, Blasco JA, Andradas E et al: Systematic review of laparoscopic versus open

[119] Delaney CP, Marcello PW, Sonoda T et al: Gastrointestinal recovery after laparoscopic

[120] Senagore AJ, Duepree HJ, Delaney CP et al: Results of a standardized technique and

[121] Raue W, Haase O, Junghans Tet al: ''Fast-track'' multimodal rehabilitation program

[122] Schwenk W, Haase O Neudecker JJ et al: Short term benefits for laparoscopic colorectal resection. Cochrane Database Syst Rev 2005; Issue 3: CD003145. [123] King PM, Blazeby JM, Ewings P et al: Randomized clinical trial comparing

[124] Callery MP: Preoperative Steroids for Laparoscpic Surgery. Ann Surg 2003; Vol 238(5):

[125] Wangensteen OH & Paine JR: Treatment of acute intestinal obstruction by suction with

[126] Cheatham ML, Chapman WC, Key SP et al: A Meta-Analysis of Selective Versus

[127] Verma R & Nelson RL: Prophylactic nasogastric decompression after abdominal

[128] Olesen KL, Birch M, Bardram L et al: Value of nasogastric tube after colorectal surgery.

[129] Nelson R, Edwards S & Tse B: Prophylactic nasogastric decompression after abdominal surgery. Cochrane Database Syst Rev 2007; Issue 3: CD004929. [130] Shires T, Williams J & Brown F: Acute Change in Extracellular Fluids Associatied with

[131] Nielsen OM & Engell HC. Changes in extracellular sodium content after elective

[132] Mecrey PM, Barden RP & Ravdis IS: Nutritial edema: its effect on the gastric emptying

[133] Lobo DN, Bostock KA, Neal KR et al: Effect of salt and water balance on recovery of

[134] More FD: Metabolic Care of the Surgical Patient. Philadelphia: WB Saubders Co 1959. [135] Holte K, Sharrock NE & Kehlet H: Pathophysiology and clinical implications of

[136] Tambyraja AL, Sengupta F, MacGregor AB et al: Patterns and clinical outcomes

gastrointestinal function after elective colonic resection: a randomised controlled

associated with routine intravenous sodium and fluid administration after

surgery. Cochrane Database Syst Rev 2007; Issue 3: CD004929.

Major Surgical Procedures. Ann Surg 1961; Nov: 803-10.

perioperative fluid excess. Br J Ane 2002; 89(4):622-32.

colorectal resection. World J Surg 2004;28: 1046-51.

abdominal vascular surgery. Acta Chir Scand 1986; 152:587-91.

time before and after gastric operations. Surgery 1937; 1: 53-64.

colectomy: results of a prospective, observational, multicenter study. Surg Endosc

postoperative care plan for laparoscopic sigmoid colectomy: a 30-month

improves outcome after laparoscopic sigmoidectomy A controlled prospective

laparoscopic and open surgery for colorectal cancer within an enhanced recovery

Routine Nasogastric Decompression After Elective Laparotomy. Ann Surg 1995;

surgery for colorectal cancer. Br J Surg 2006; 93: 921–928

experience. Dis Colon Rectum. 2003 Apr;46(4):503-9.

evaluation Surg Endosc (2004) 18: 1463–1468

programme. Br J Surg 2006; 93: 300–308.

Acta Chir Scand. 1984;150(3):251-3.

trial. Lancet 2002; 359(May):1812-18.

the duodenal tube. JAMA 1933; 101(20):1532-1539.

2010; 24: 653-61.

661-2.

Vol 221(5): 469-78.


### **Postoperative Ileus in Elective Colorectal Surgery: Management Strategies**

J. Ahmed, S. Mehmood and J. MacFie *Scarborough General Hospital, Scarborough United Kingdom*

### **1. Introduction**

34 Contemporary Issues in Colorectal Surgical Practice

[156] Sammour T, Zargar-Shoshtari K, Bhat A et al: A programme of Enhanced Recovery

[157] King PM, Blazeby JM, Ewings P et al: The influence of an Enhanced Recovery

[159] Stephen AE & Berger DL: Shortened length of stay and hospital cost reduction with

[160] Lassen K, Hannemann P, Ljungqvist O et al: Patterns in current perioperative practice:

[161] Grol R & Grimshaw J; From best evidence to best practice: effective implementation of

change in patient's care. Lancet. 2003 Oct 11; 362(9391):1225-30.

colorectal cancer. Colorectal Dis 2006; Vol 8(6): 506-13. [158] Kehlet H: Fast-track colorectal surgery. Lancet 2008: Vol 371: 791-3.

resection. Surgery 2003; Mar; 133(3): 277-82.

NZMJ 2010; 123(1319): 61-70.

2005;330:1420–1

After Surgery (ERAS) is a cost-effective intervention in elective colonic surgery.

Programme on clinical outcomes, costs and quality of life after surgery for

implementation of an accelerated clinical care pathway after elective colon

survey of colorectal surgeons in five northern European countries. BMJ

Postoperative ileus (POI) is a condition characterised by transient interruption of gut function following surgical intervention. Ileus develops due to impaired motility of the gastrointestinal tract in the absence of any mechanical bowel obstruction (Holte and Kehlet 2000). This results in disturbance of coordinated propulsive action leading to accumulation of luminal gas and fluid mainly within small bowel. Clinically it is manifested by abdominal distension, nausea, vomiting and diet intolerance (Lubawski and Saclarides 2008; Parvizi, et al. 2008).

Despite a number of advances in perioperative care and surgical techniques, POI remains one of the commonest challenges in surgery. Although most commonly seen following abdominal surgery, it is also associated with extra-abdominal operations such as cardiothoracic and orthopaedic procedures (Parvizi, et al. 2008; Stewart and Waxman 2010). Historically, POI has been regarded as an inevitable event after major abdominal surgery and it is considered the single largest factor prolonging the length of hospital stay (LOS) following gastrointestinal surgery (Lubawski and Saclarides 2008). It impacts greatly on patient's recovery even after uncomplicated abdominal surgery. Similarly, postoperative ileus is one of the commonest factors affecting healthcare costs in surgical patients. Furthermore, POI causes significant frustration amongst the patients and the surgeons alike (Asgeirsson, et al. 2010).

In recent years, some progress has been made in understanding of underlying causative mechanisms of POI. The multifaceted pathophysiology of POI includes neurogenic, hormonal, inflammatory and pharmacological factors which have been targeted to reduce the incidence and duration of POI. However, there is no definitive treatment to prevent this condition. Key principles in the prevention and management of POI pertain to minimising surgical trauma and preserving normal physiological functions, including gut function. Evidence suggests that this is best achieved by a multimodal approach involving a host of interventions in the perioperative period. Perhaps the most significant development in recent times is the formulation of enhanced recovery after surgery (ERAS) protocols. ERAS protocols provide a multimodal approach to optimising perioperative care and enhancing postoperative recovery. Likewise, minimally invasive surgery i.e. laparoscopic approach has been shown to provide benefits like reduction in length of stay in hospital. Similarly, newer pharmacological therapies (e.g. Mu-opioid receptor antagonist) have shown promising results, however, more scientific evidence is awaited in this area.

In this chapter, we give an account of pathophysiology, natural history, and classification of ileus. Different strategies to prevent and manage POI such as ERAS protocols, minimally invasive surgery and pharmacological approaches are discussed.

### **2. History and definitions of POI**

Ileus is a Greek word which literally means "obstructed" however it is referred to as a functional impediment without mechanical obstruction. POI has been a recognised condition for more than two centuries. The exact definition of POI has been a topic for debate for over a century. It was suggested by Finney in 1906 to divide the phenomnon of ileus into pathophysiological, mechanical, septic or adynamic ileus (Finney 1906). One hundred years later in 2006, the '*Postoperative Ileus Management Council' (PIMC)* was formed by experts in the field of surgery and anaesthesia. The PIMC collected all scientific evidence and developed a consensus on the definition of POI. According to this panel POI is a:

"*transient cessation of coordinated bowel motility after surgical intervention, which prevents effective transit of intestinal contents or tolerance of oral intake".*

The PIMC categorised POI into primary and secondary ileus. Primary POI develops in the absence of any precipitating factors (i.e. absence of any complications), while secondary POI develops in the presence of a complication such as wound infection, intra-abdominal collection, anastomotic leak, and sepsis etc. In addition, a further three types of POI were described based on the part of gastrointestinal tract (GIT) involved. Type–I POI involves all part of the GIT and thus called pan-intestinal ileus. Clinically it is manifested as nausea and vomiting along with absence of bowel movement or passage of flatus. Type–II POI affects only the upper GIT and manifests as nausea and vomiting. These patients are able to tolerate food but are unable to pass flatus. Type–III POI comprises of ileus of the lower GIT. The patients may be able to tolerate food but are unable to pass flatus or have a bowel motion (Delaney C 2006).

The duration of POI and the cardinal features of its resolution are important aspects which need careful consideration. The minimum time period following surgery before ileus develops is not well defined. Animal and human models have shown that return of gut function occurs first of all in small bowel (24 hours) followed by stomach (48 hours) and colon (48 to 72 hours) (Lubawski and Saclarides 2008). It has been suggested that the colon may take up to 120 hours to resume normal peristaltic activities postoperatively. (Miedema and Johnson 2003).

The return of gut function is historically assessed by either of the presence of bowel sounds, passage of flatus or stool, or tolerance to oral food. Passage of flatus or stool and/or presence of bowel sounds are considered as the benchmark criteria for the recovery of bowel function. However, concerns have been expressed about the validity and accuracy in recording these signs. For example, presence of bowel sounds does not necessarily indicate return of propulsive activities of the whole bowel as they may only represent small bowel activity without colonic peristalsis (Holte and Kehlet 2000). In addition, accuracy of recording these features is usually low. To record presence of bowel sounds requires frequent auscultation which is practically difficult. Similarly, passage of flatus is also not the ideal end point. Some patients are simply not comfortable to report it whereas others may not be able to recall passing flatus in the postoperative peroid. The passage of stool is also considered to have low specificity. A patient might report having a bowel movement which would be representing distal bowel evacuation as opposed to global gastrointestinal tract function. Hence determination of the end of postoperative ileus is another contentious issue.

The combination of all three signs (i.e. presence of bowel sounds, passage of stool or flatus along with tolerance of oral feed) provides higher accuracy in confirming resolution of POI. Thus, based on the available evidence and PIMC consensus report the resolution of POI can be defined:

*"the duration of POI is the time from the surgery until passage of stool or flatus and until oral feed that is tolerated and maintained during 24 hours"*.

However, it is important to appreciate that uncertainties in criteria for the resolution of POI have impact on the conclusions of various studies published in the literature (Boeckxstaens and de Jonge 2009).

### **3. Pathophysiology of post-operative ileus**

### **3.1 Normal physiology**

36 Contemporary Issues in Colorectal Surgical Practice

In this chapter, we give an account of pathophysiology, natural history, and classification of ileus. Different strategies to prevent and manage POI such as ERAS protocols, minimally

Ileus is a Greek word which literally means "obstructed" however it is referred to as a functional impediment without mechanical obstruction. POI has been a recognised condition for more than two centuries. The exact definition of POI has been a topic for debate for over a century. It was suggested by Finney in 1906 to divide the phenomnon of ileus into pathophysiological, mechanical, septic or adynamic ileus (Finney 1906). One hundred years later in 2006, the '*Postoperative Ileus Management Council' (PIMC)* was formed by experts in the field of surgery and anaesthesia. The PIMC collected all scientific evidence

"*transient cessation of coordinated bowel motility after surgical intervention, which prevents effective* 

The PIMC categorised POI into primary and secondary ileus. Primary POI develops in the absence of any precipitating factors (i.e. absence of any complications), while secondary POI develops in the presence of a complication such as wound infection, intra-abdominal collection, anastomotic leak, and sepsis etc. In addition, a further three types of POI were described based on the part of gastrointestinal tract (GIT) involved. Type–I POI involves all part of the GIT and thus called pan-intestinal ileus. Clinically it is manifested as nausea and vomiting along with absence of bowel movement or passage of flatus. Type–II POI affects only the upper GIT and manifests as nausea and vomiting. These patients are able to tolerate food but are unable to pass flatus. Type–III POI comprises of ileus of the lower GIT. The patients may be able to tolerate food but are unable to pass flatus or have a bowel

The duration of POI and the cardinal features of its resolution are important aspects which need careful consideration. The minimum time period following surgery before ileus develops is not well defined. Animal and human models have shown that return of gut function occurs first of all in small bowel (24 hours) followed by stomach (48 hours) and colon (48 to 72 hours) (Lubawski and Saclarides 2008). It has been suggested that the colon may take up to 120 hours to resume normal peristaltic activities postoperatively. (Miedema

The return of gut function is historically assessed by either of the presence of bowel sounds, passage of flatus or stool, or tolerance to oral food. Passage of flatus or stool and/or presence of bowel sounds are considered as the benchmark criteria for the recovery of bowel function. However, concerns have been expressed about the validity and accuracy in recording these signs. For example, presence of bowel sounds does not necessarily indicate return of propulsive activities of the whole bowel as they may only represent small bowel activity without colonic peristalsis (Holte and Kehlet 2000). In addition, accuracy of recording these features is usually low. To record presence of bowel sounds requires frequent auscultation which is practically difficult. Similarly, passage of flatus is also not the ideal end point. Some patients are simply not comfortable to report it whereas others may not be able to recall passing flatus in the postoperative peroid. The passage of stool is also

and developed a consensus on the definition of POI. According to this panel POI is a:

invasive surgery and pharmacological approaches are discussed.

**2. History and definitions of POI** 

*transit of intestinal contents or tolerance of oral intake".*

motion (Delaney C 2006).

and Johnson 2003).

The normal motility of gut is maintained by the complex interaction among the central nervous system, enteric nervous system, and hormonal and local factors directly acting on the intestinal smooth muscle (Livingston and Passaro 1990; Mattei and Rombeau 2006). The autonomic nerve system consists of parasympathetic, sympathetic and enteric nervous systems. It has a profound effect on gut motility, ion transportation and is involved in secretory and absorptive processes within GIT. The parasympathetic part of the nervous system is provided by vagus (proximal GIT) and pelvic parasympathetic (distal GIT) nerves. These nerve fibres have a stimulating effect on GIT. The sympathetic innervation is provided by the splanchnic nerve. These post-ganglionic fibres run along the arteries and synapse with the myenteric plexus on the gut wall. The sympathetic nerve fibres have an inhibitory effect on gut which includes inhibition of secretions and motility, and constriction of sphincters and blood vessels. The animal models have shown the sympathetic control is dominant over parasympathetic (Livingston and Passaro 1990).

The enteric nervous system, which is also known as the intrinsic nervous system, consists of myenteric and submucosal plexuses. It makes an important contribution in controlling GI motility and coordinating relaxation and contraction of smooth muscle. The myenteric plexus mainly controls motility of the digestive tract, whilst the submucosal plexus mainly regulates the gastrointestinal blood flow and epithelial function. The enteric nervous system consists of sensory, motor and interneurons. Acetylcholine is the major neurotransmitter which is produced by enteric neurons. Although, the enteric nervous system has the ability to function independently, for normal digestive process it links with the central (extrinsic) nervous system. Due to these cross connections gut provides sensory information to the central nervous system and therefore it may recieve efferent signals from it (Boeckxstaens and de Jonge 2009; Luckey, et al. 2003; Wood 2008). In addition, various hormones and enzymes play an important role in gut function and its motility. The gastrointestinal tract is the largest endocrine organ, called enteric endocrine system, with endocrine glands diffusely scattered throughout the GIT. The hormones secreted by these glands work by a negative feedback mechanism. The enteric endocrine system and nervous systems (enteric and autonomic nervous systems) work in a coordinated way to maintain the regular contractions of smooth muscle. It has two specific patterns: slow wave and spike potentials. The spike potentials are true action potentials which trigger the muscle contraction. The motility of stomach and small bowel varies according to fed and fasting states. Further, in fed state the number of contractions, their intensity and duration are based on the food ingested. During fasting state the migrating motor complex (MMC) dictates the pattern of bowel contraction (Luckey, et al. 2003). Due to MMC, the remnants of meal, bacterial and other debris are pushed into the large intestine. Hence they have housekeeping function and prevent bacterial overgrowth in the small intestine. Thus any imbalance in autonomic nerves system, enteric endocrine and the local environment may impair the normal gut motility and digestive process, and may lead to ileus.

### **3.2 Pathophysiology**

Ileus is caused by temporary inhibition of extrinsic motility regulation and is more prominent in the colon, while paralytic ileus involves all or part of the GIT and is caused by the inhibition of local and intrinsic contractile systems along with extrinsic inhibition (Bauer and Boeckxstaens 2004). Hence each local factor, autonomic nervous system and hormonal effect has an independent role in the development of POI.

In the past, surgical stress was considered to cause POI by increasing serum catecholamine concentration which would inhibit the gut motility and augment sympathetic activity (Smith, et al. 1977). However, experiments on animal models have shown that although adrenalectomy reduces the level of catecholamine, it does not improve POI. In contrast, splanchnicectomy partially improves ileus (Dubois, et al. 1975). These findings support the hypothesis that the sympathetic nervous system is independent of adrenal activity in causing ileus (Livingston and Passaro 1990). Similarly, vasopressin inhibits intestinal motility (Mitchell and Collin 1985). It is released as a part of stress response following surgical trauma and after the use of opiates (Cochrane, et al. 1981); (Weiskopf, et al. 1987). The exact mechanism by which vasopressin mediates dysmotility is not clear. However, it is suggested that vasopressin is related to reduction in mesenteric blood flow which may subsequently cause impairment of gastrointestinal motility (Livingston and Passaro 1990).

Evidence suggests that three major mechanisms play important role in the development of POI, namely; neurogenic, inflammatory and pharmacological mechanisms. Either of these can cause ileus independently, as does their cumulative effect (Bauer and Boeckxstaens 2004).

### **3.2.1 Neurogenic mechanisms**

In 1872, Golz suggested that intestinal contractility increases after division of the neural axis. This was one of the first observations suggesting the presence of inhibitory spinal reflexes (Bauer and Boeckxstaens 2004). Later evidence has shown that splanchnicectomy improves bowel contraction after laparotomy. It was further suggested that splanchnic afferents are largely involved during gastrointestinal surgery, rather than vagal afferents, leading to hypomotility after surgical intervention (Bauer and Boeckxstaens 2004).

Recent investigations found that different neural pathways are activated during abdominal surgery. Their pathways depend upon the part of GIT involved and the intensity of nociceptive stimulus. For instance, skin incision and laparotomy activate an adrenergic inhibitory pathway, which is a low threshold spinal reflex and reduces gut motility (Boeckxstaens, et al. 1999). Strong stimuli, such as manipulation of the intestine, may activate an additional high-threshold supraspinal pathway (Barquist, et al. 1996). The corticotrophin-releasing factor (CRF) also plays a central role in this pathway. CRF antagonist has been shown to prevent gastric ileus (Bonaz and Tache 1997). Along with these there are non-adrenergic, vagally mediated, inhibitory pathways triggered by intense stimulation of splanchnic afferent fibres (Boeckxstaens, et al. 1999). Animal models have shown that nitric oxide (NO) is a most potent neurotransmitter in non-adrenergic pathways (Boeckxstaens, et al. 1999; De Winter, et al. 1997). Similarly, vasoactive intestinal peptide (VIP) acts as an inhibitory neurotransmitter during surgical stress (Boeckxstaens, et al. 2000; De Winter, et al. 1998).

Other studies have shown that μ-opioid receptor agonists (e.g morphine) prolong the duration of POI and k-opioid receptor agonists, such as fedotosine, resolve ileus through a peripheral action on non-vagal sensory afferent (Gue, et al. 1989). It is suggested that activation of k-opioid receptors on splanchnic afferent reduces POI by decreasing visceral nociception and inhibitory reflexes. The neural mechanism is primarily activated during the first few hours after surgery and cannot account of POI that lasts for days (Holte and Kehlet 2000; Reissman, et al. 1996).

### **3.2.2 Inflammatory mechanisms**

38 Contemporary Issues in Colorectal Surgical Practice

the regular contractions of smooth muscle. It has two specific patterns: slow wave and spike potentials. The spike potentials are true action potentials which trigger the muscle contraction. The motility of stomach and small bowel varies according to fed and fasting states. Further, in fed state the number of contractions, their intensity and duration are based on the food ingested. During fasting state the migrating motor complex (MMC) dictates the pattern of bowel contraction (Luckey, et al. 2003). Due to MMC, the remnants of meal, bacterial and other debris are pushed into the large intestine. Hence they have housekeeping function and prevent bacterial overgrowth in the small intestine. Thus any imbalance in autonomic nerves system, enteric endocrine and the local environment may

Ileus is caused by temporary inhibition of extrinsic motility regulation and is more prominent in the colon, while paralytic ileus involves all or part of the GIT and is caused by the inhibition of local and intrinsic contractile systems along with extrinsic inhibition (Bauer and Boeckxstaens 2004). Hence each local factor, autonomic nervous system and hormonal

In the past, surgical stress was considered to cause POI by increasing serum catecholamine concentration which would inhibit the gut motility and augment sympathetic activity (Smith, et al. 1977). However, experiments on animal models have shown that although adrenalectomy reduces the level of catecholamine, it does not improve POI. In contrast, splanchnicectomy partially improves ileus (Dubois, et al. 1975). These findings support the hypothesis that the sympathetic nervous system is independent of adrenal activity in causing ileus (Livingston and Passaro 1990). Similarly, vasopressin inhibits intestinal motility (Mitchell and Collin 1985). It is released as a part of stress response following surgical trauma and after the use of opiates (Cochrane, et al. 1981); (Weiskopf, et al. 1987). The exact mechanism by which vasopressin mediates dysmotility is not clear. However, it is suggested that vasopressin is related to reduction in mesenteric blood flow which may subsequently cause impairment of gastrointestinal motility (Livingston and Passaro 1990). Evidence suggests that three major mechanisms play important role in the development of POI, namely; neurogenic, inflammatory and pharmacological mechanisms. Either of these can cause ileus independently, as does their cumulative effect (Bauer and Boeckxstaens

In 1872, Golz suggested that intestinal contractility increases after division of the neural axis. This was one of the first observations suggesting the presence of inhibitory spinal reflexes (Bauer and Boeckxstaens 2004). Later evidence has shown that splanchnicectomy improves bowel contraction after laparotomy. It was further suggested that splanchnic afferents are largely involved during gastrointestinal surgery, rather than vagal afferents, leading to

Recent investigations found that different neural pathways are activated during abdominal surgery. Their pathways depend upon the part of GIT involved and the intensity of nociceptive stimulus. For instance, skin incision and laparotomy activate an adrenergic

hypomotility after surgical intervention (Bauer and Boeckxstaens 2004).

impair the normal gut motility and digestive process, and may lead to ileus.

effect has an independent role in the development of POI.

**3.2 Pathophysiology** 

2004).

**3.2.1 Neurogenic mechanisms** 

The inflammatory response develops mainly at a local level and is associated directly with the development of POI (Bauer and Boeckxstaens 2004). For this local inflammatory response, muscularis externa provides a unique immunological compartment containing a rich network of macrophages (Faussone-Pellegrini, et al. 1990; Mikkelsen 1995). These macrophages secrete a number of inflammatory mediators such as cytokines, nitric oxide (NO), prostaglandins, and defensins (Cicalese, et al. 1996; Kagan, et al. 1994). Surgical manipulation of bowel activates the macrophages in muscularis externa stimulating release of above inflammaotory mediators (Kalff 1999; Schwarz, et al. 2001).

Intestinal manipulation also provokes the release of tumour necrosis factor-α (TNF-α), monocyte chemotactic protein-1, interleukin-1b and interleukin-6. These pro-inflammatory cytokines up-regulate adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1). This molecular response expands to cellular level and recruits more leucocytes (monocytes and neutropils) into the muscularis externa that further release NO, cytokines, reactive oxygen intermediates and proteases (Kalff, et al. 1999). The role of NO and prostaglandins in the development of POI has been shown in pharmacological and genetic studies ((Kalff 1999; Schwarz, et al. 2001). There is strong association between neural and inflammatory mechanisms as discussed below.

#### **3.2.2.1 Inflammatory–neuronal interaction**

It is well established that intestinal manipulation mediates local inflammation which causes inhibition of smooth muscle function. The manipulation of the small bowel not only causes ileus in the small bowel, it is also linked with delayed gastric emptying (de Jonge, et al. 2003). This raises the question as to whether there is any other mechanism which affects motility distant from the site of inflammation or manipulation? Bauer and Boeckxstaens (2004), suggested that:

*"One possible mechanism could be an interaction between the inflammatory milieu of the postoperative muscularis and primary afferent neuronal activity, triggering the neural inhibitory pathways"*.

Animal models show that the delay in gastric emptying is induced by intestinal manipulation which occurs through an inhibitory adrenergic pathway. Up-regulation of cyclooxygenase-2 (COX-2) releases prostaglandins that participate in local inflammation and the development of POI (Schwarz, et al. 2001). A number of experimental studies have suggested that prostaglandins act as neuromodulators and their levels increase significantly following surgery. Animal models treated with selective COX-2 inhibitors show a reduction in incidence of ileus. Based on the findings of such studies Bauer and Boeckxstaens (2004) also concluded that:

*"the intestinal inflammation in response to bowel manipulation results in primary afferent activation, initiating subsequent inhibitory motor reflexes to the gut, and leading to postoperative intestinal gut dysfunction, with prostaglandins playing a crucial role".* 

Furthermore, intestinal manipulation activates mast cells which play a vital role in the development of inflammation. During surgery even a gentle manipulation of intestine triggers the release of mast cell mediators. The activated mast cells release potent pro-inflammatory mediators such as TNF-α, protease and histamine which contribute to the inflammatory response. In addition, these mediators recruit more leucocytes and up-regulate adhesion molecules, all taking part in inflammatory process (Kubes and Kanwar 1994; Wershil, et al. 1996). The activated mast cells briefly increase intestinal permeability resulting in translocation of bacteria and consequently activation of resident macrophages in the muscularis externa. An inhibitory adrenergic neural pathway is also activated which impairs the neuromuscular function of the distant part of intestine, explaining the generalised features of ileus (Boeckxstaens and de Jonge 2009). Studies have demostrated that mast cell stabilizers improve gastric emptying and reduce inflammatory response (de Jonge, et al. 2003). Hence mast cells and resident macrophages are mainly responsible for activation of the innate immune system, leading to an inflammatory response after intestinal manipulation.

### **3.2.3 Pharmacological mechanisms**

There are two types of opiates: endogenous and exogenous. Both play an important role in gastrointestinal dysmotility. Both are simliar and exert their actions through same opoid receptors (Prasad and Matthews 1999). Overall, opiates have an inhibitory effect which leads to impairment in gut motility, its secretions, and the transport of fluid and electrolytes across the gut wall. Understandibly, such actions lead to a delay in gastric emptying and inhibition of intestinal peristalsis and the development of POI (Kurz and Sessler 2003). This phenomenon has been proven in a number of studies on animal and human models which have shown that δ and μ opioid agonists diminish peristalsis (Bauer, et al. 1991; Bauer AJ 1991).

There are three different types of opoid receptors: δ (delta), μ (mu) and қ (kappa). Opiates have a receptor-specific effect on intestine and hence they mainly affect μ- receptors on GIT, while it has less effect on other organs receptors such as the brain or spinal cord. This is why morphine has more of a constipating effect than an analgesic effect. The requirement of morphine is four times more likely to increase to have an analgesic effect than constipating effect (4:1 ratio) (Holte and Kehlet 2000; Kalff, et al. 1998). Therefore, when opiates are used

*"One possible mechanism could be an interaction between the inflammatory milieu of the postoperative muscularis and primary afferent neuronal activity, triggering the neural inhibitory* 

Animal models show that the delay in gastric emptying is induced by intestinal manipulation which occurs through an inhibitory adrenergic pathway. Up-regulation of cyclooxygenase-2 (COX-2) releases prostaglandins that participate in local inflammation and the development of POI (Schwarz, et al. 2001). A number of experimental studies have suggested that prostaglandins act as neuromodulators and their levels increase significantly following surgery. Animal models treated with selective COX-2 inhibitors show a reduction in incidence of ileus. Based on the findings of such studies Bauer and Boeckxstaens (2004)

*"the intestinal inflammation in response to bowel manipulation results in primary afferent activation, initiating subsequent inhibitory motor reflexes to the gut, and leading to postoperative* 

Furthermore, intestinal manipulation activates mast cells which play a vital role in the development of inflammation. During surgery even a gentle manipulation of intestine triggers the release of mast cell mediators. The activated mast cells release potent pro-inflammatory mediators such as TNF-α, protease and histamine which contribute to the inflammatory response. In addition, these mediators recruit more leucocytes and up-regulate adhesion molecules, all taking part in inflammatory process (Kubes and Kanwar 1994; Wershil, et al. 1996). The activated mast cells briefly increase intestinal permeability resulting in translocation of bacteria and consequently activation of resident macrophages in the muscularis externa. An inhibitory adrenergic neural pathway is also activated which impairs the neuromuscular function of the distant part of intestine, explaining the generalised features of ileus (Boeckxstaens and de Jonge 2009). Studies have demostrated that mast cell stabilizers improve gastric emptying and reduce inflammatory response (de Jonge, et al. 2003). Hence mast cells and resident macrophages are mainly responsible for activation of the innate immune system,

There are two types of opiates: endogenous and exogenous. Both play an important role in gastrointestinal dysmotility. Both are simliar and exert their actions through same opoid receptors (Prasad and Matthews 1999). Overall, opiates have an inhibitory effect which leads to impairment in gut motility, its secretions, and the transport of fluid and electrolytes across the gut wall. Understandibly, such actions lead to a delay in gastric emptying and inhibition of intestinal peristalsis and the development of POI (Kurz and Sessler 2003). This phenomenon has been proven in a number of studies on animal and human models which have shown that

There are three different types of opoid receptors: δ (delta), μ (mu) and қ (kappa). Opiates have a receptor-specific effect on intestine and hence they mainly affect μ- receptors on GIT, while it has less effect on other organs receptors such as the brain or spinal cord. This is why morphine has more of a constipating effect than an analgesic effect. The requirement of morphine is four times more likely to increase to have an analgesic effect than constipating effect (4:1 ratio) (Holte and Kehlet 2000; Kalff, et al. 1998). Therefore, when opiates are used

*intestinal gut dysfunction, with prostaglandins playing a crucial role".* 

leading to an inflammatory response after intestinal manipulation.

δ and μ opioid agonists diminish peristalsis (Bauer, et al. 1991; Bauer AJ 1991).

**3.2.3 Pharmacological mechanisms** 

*pathways"*.

also concluded that:

repeatedly, patients develop a tolerance to analgesic effect but not to the side effects on GIT (Holte and Kehlet 2000). A prospective study performed by Cali and colleagues did not show any significant correlation between the length of incision and the dose of morphine taken. However, it suggested that the dose of morphine is directly related to the return of gut function (Cali, et al. 2000). Similarly, opiates bind to leucocytes and affect the immune system which slows down gut motility. They also facilitate NO synthesis which plays a significant part in the pathogenesis of POI. Release of various hormones also plays a role in the pathogenesis of ileus. For example, corticotrophin-releasing factor stimulates inflammatory mediators in the bowel (Tache, et al. 1993).

In summary, there are multiple factors which contribute to the pathogenesis of POI and major mechanisms include neurogenic, inflammatory, pharmacological and hormonal responses (figure 1).

Fig. 1. Pathogenesis of post-operative ileus

### **4. Strategies to reduce POI**

Over the past two decades, a number of strategies have been introduced to improve the quality of peroperative care. Most of those were primarily directed at reducing perioperative mortality, morbidity and LOS in hospital. All of those were aimed to prevent ileus by minimising the stress response and maintaining the normal body physiology during and after surgery. These include ERAS programmes, laparoscopic surgical approaches and the use of specific pharmaceutical agents. In this section, different strategies to prevent and manage POI are discussed.

### **4.1 Modalities to manage POI**

### **4.1.1 Enhanced Recovery After Surgery (ERAS) protocols**

ERAS protocols involve a series of measures taken pre-, per- and post-operatively which collectively ease the stress response to surgical trauma and enhance post-operative recovery. It has been shown that this 'multimodal rehabilitation' programme improves surgical outcome and patient satisfaction after elective surgery (Khoo, et al. 2007; Varadhan, et al. 2010; Wind, et al. 2006b). ERAS programme consists of a number of elements which are summarised in Figure- 2.

Fig. 2. MBP- Mechanical Bowel Preparation, T and C- Transverse and curve , NG- Nasogastric, PONV- prevention of nausea and vomiting. (Authors previously published this figure as Ahmed J et al, Colorectal Disease, 2011 Oct 11. doi: 10.1111/j.1463- 5 1318.2011.02856.x.)

### **4.1.2 Pre-operative components of ERAS protocols**

Preoperative patient counselling and education prior to surgery is important aspect of ERAS protocols*.* Along with counselling, patients should also see other members of the multidisciplinary team such as dieticians, stoma care nurses and nutrition nurses. Recently, a number of centres have introduced a dedicated ERAS nurse who provides information regarding ERAS pathways and the various stages during and after surgery. An important component of preoperative phase is the ingestion of carbohydrate-rich drink the night before and on the morning of surgery. A short period of fasting and carbohydrate loading both help in maintaining patients' nitrogen balance and reducing post-operative insulin resistance (Soop, et al. 2004; Svanfeldt, et al. 2007).

Pre-operative phase

Pre-operative phase

Fig. 2. MBP- Mechanical Bowel Preparation, T and C- Transverse and curve , NG- Nasogastric, PONV- prevention of nausea and vomiting. (Authors previously published this figure as Ahmed J et al, Colorectal Disease, 2011 Oct 11. doi: 10.1111/j.1463- 5 1318.2011.02856.x.)

Preoperative patient counselling and education prior to surgery is important aspect of ERAS protocols*.* Along with counselling, patients should also see other members of the multidisciplinary team such as dieticians, stoma care nurses and nutrition nurses. Recently, a number of centres have introduced a dedicated ERAS nurse who provides information regarding ERAS pathways and the various stages during and after surgery. An important component of preoperative phase is the ingestion of carbohydrate-rich drink the night before and on the morning of surgery. A short period of fasting and carbohydrate loading both help in maintaining patients' nitrogen balance and reducing post-operative insulin

**4.1.2 Pre-operative components of ERAS protocols** 

Post-operative phase

resistance (Soop, et al. 2004; Svanfeldt, et al. 2007).

Oral mechanical bowel preparation should be avoided in patients undergoing elective bowel surgery. A single phosphate enema can be used on the days of surgery to clear the rectum in patients undergoing left-sided anastomosis. A Cochrane review suggested that low molecular weight heparin (LMWH) and graduated compression thromboembolic deterrent stockings (TEDs) are the most effective anti-thrombotic prophylaxis (Wille-Jorgensen, et al. 2003). A single dose of broad spectrum antibiotics reduces the risk of wound infection and should be administered prior to skin incision.

### **4.1.3 Peri-operative components of ERAS protocols**

High inspired oxygen concentrations (80%) should be administered during anaesthesia and in the early post-operative period (for a minimum of six hours). Oxygen molecules are required for the production of free radicals, which play an important role in the defence mechanism against pathogens to reduce surgical site infection, and in the synthesis of collagen for wound healing and angiogenensis (Allen, et al. 1997; Hopf, et al. 1997; Qadan, et al. 2009). In addition, high concentration of oxygen in the tissues during the immediate post-operative period improves perfusion at the anastomotic site and may also be associated with a reduction in post-operative nausea and vomiting (PONV) (Greif, et al. 1999; Orhan-Sungur, et al. 2008)**.** 

The core temperature should be measured and monitored using an oesophageal probe. In patients undergoing prolonged surgery (i.e., more than one hour) warmed intravenous fluid should be administered (Lindwall, et al. 1998; Smith, et al. 1998).

Hypothermia (core temperature less than 36°C) causes tissue hypoxia due to peripheral vasoconstriction which increases the risk of coagulopathy, wound infections and cardiac complications (Frank, et al. 1997; Ozaki, et al. 1995; Schmied, et al. 1996). It is also linked to a change in immune response and an increase in catabolic response (Frank, et al. 1995). Prevention of hypothermia in the peri-operative phase has been shown to decrease blood loss, and cardiac and infective complications (Melling, et al. 2001; Wong, et al. 2007).

Goal directed intra-operative intravenous fluid administration has shown positive impact on early return of gut function and reduction in length of stay in hospital. Oesophageal Doppler or LiDCO plus™ and LiDCO rapid™ are minimally invasive methods used to measure the cardiac output and stroke volume. These devices enable the anaesthetist to tailor the fluid requirement (goal directed) according to changes in cardiac output peroperatively. Goal directed fluid therapy has been shown to result in early return of gastric motility, reduction in time to defecation and an improved tolerance to oral feed due to reduced gut oedema (Gan, et al. 2002; Lobo, et al. 2002; Nisanevich, et al. 2005) . Splanchnic hypoperfusion, which may remain unnoticed with traditional monitoring, results in delayed return of gut function. It may lead to bacterial translocation across the gut wall and sepsis (Mythen and Webb 1994). Similarly, an excessive amount of intravenous fluid during surgery may cause the development of gut oedema which may also result in the delay in return of gut function (Grocott, et al. 2005).

The concept of minimally invasive surgery is recommended which includes both open (small and appropriate incisions) as well as laparoscopic approach. In open approach, a transverse, limited midline, oblique or paramedian incision should be used whenever possible. Such small transverse or mini-laparotomy incisions may have positive impact on analgesic requirement, pulmonary complications, systemic inflammatory response and length of stay in hospital (Nakagoe, et al. 2001; Nakagoe, et al. 2004; Takegami, et al. 2003; Werawatganon and Charuluxanun 2005). In ERAS protocol, routine use of nasogastric tubes and abdominal drains following GI surgery is not recommended. A Cochrane review (33 studies, 5240 patients) has suggested that there was an earlier return of gut function, reduction in pulmonary complications and an insignificant trend towards increased risk of wound infection in patients not having routine nasogastric tube. However, no difference in the rates of anastomotic dehiescence was demonstrated. Its use is also associated with pain and discomfort to patient and impedes post-operative mobility (Nelson, et al. 2007; Nelson, et al. 2005). Similarly, several randomised studies and meta-analyses have suggested that the routine use of drains does not confer any clinical advantage in the early detection of anastomotic leak or intra-abdominal collection (Jesus, et al. 2004; Karliczek, et al. 2006; Urbach, et al. 1999)**.** 

It is recommended that all patients undergoing open abdominal surgery should have high thoracic epidural analgesia. Patient should receive epidural analgesia for at least 12 hours to a maximum of 48 hours. Ideally weaning form epidural should start 12 hours after operation.

However, in laparoscopic colorectal surgery the benefits of epidural analgesia are not clear. It may be used depending upon the preference of the operating surgeon and anaesthetist. The epidural anaesthesia blocks sympathetic reflexes and afferent stimuli. This attenuates the post-operative stress and promotes early return of gut function which reduces incidence of PIO (Holte and Kehlet 2002; Marret, et al. 2007). It is important to note that epidural analgesia may cause hypotension due to vasodilatation which may have an adverse affect on the anastomosis. Early recognition of these patients and monitoring in the high dependency unit is therfore critical.

Recently, other modalities such as transversus abdominis plane (TAP) blocks and wound irrigation (PainBuster®) with local anaesthetic (0.2% ropivacaine®) have shown a reduction in use of opiates and improvement in patient mobilisation in the early post-operative period (Bamigboye and Hofmeyr 2009; Beaussier, et al. 2007).

### **4.1.4 Post-operative components of ERAS protocols**

Opiates have a profound negative effect on the gut motility, consequently delaying return of gut function and prolonging the duration of POI. Regular use of Paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDS) is recommended unless contraindicated. NSAIDS help promote gut recovery by reducing local mucosal inflammation (Cali, et al. 2000). Prophylactic antiemetics should be prescribed to those patients receiving opiates.

It is emphasised that all patients be allowed oral fluid and diet soon after surgery. Intravenous fluid should be stopped as soon as the patient's oral intake is adequate. There is now evidence to support the view that early commencement of enteral feeding is beneficial and is safe to introduce within 24 hours of surgery (Andersen, et al. 2006; Lewis, et al. 2009). Similarly, early feeding facilitates gut motility and may help in the early return of gut function and reduce the ileus.

All patients should have an enforced and structured mobilisation plan during the postoperative period. A designated physiotherapist with a mobilisation plan tailored to the individual patient's need should work closely with the patient in order to achieve best outcome. Early mobilisation is paramount in preventing venous thromboembolism (VTE), respiratory complications and reduction in muscle strength (Schuster and Montie 2002). It is

(Nakagoe, et al. 2001; Nakagoe, et al. 2004; Takegami, et al. 2003; Werawatganon and Charuluxanun 2005). In ERAS protocol, routine use of nasogastric tubes and abdominal drains following GI surgery is not recommended. A Cochrane review (33 studies, 5240 patients) has suggested that there was an earlier return of gut function, reduction in pulmonary complications and an insignificant trend towards increased risk of wound infection in patients not having routine nasogastric tube. However, no difference in the rates of anastomotic dehiescence was demonstrated. Its use is also associated with pain and discomfort to patient and impedes post-operative mobility (Nelson, et al. 2007; Nelson, et al. 2005). Similarly, several randomised studies and meta-analyses have suggested that the routine use of drains does not confer any clinical advantage in the early detection of anastomotic leak or intra-abdominal

It is recommended that all patients undergoing open abdominal surgery should have high thoracic epidural analgesia. Patient should receive epidural analgesia for at least 12 hours to a maximum of 48 hours. Ideally weaning form epidural should start 12 hours after operation. However, in laparoscopic colorectal surgery the benefits of epidural analgesia are not clear. It may be used depending upon the preference of the operating surgeon and anaesthetist. The epidural anaesthesia blocks sympathetic reflexes and afferent stimuli. This attenuates the post-operative stress and promotes early return of gut function which reduces incidence of PIO (Holte and Kehlet 2002; Marret, et al. 2007). It is important to note that epidural analgesia may cause hypotension due to vasodilatation which may have an adverse affect on the anastomosis. Early recognition of these patients and monitoring in the high

Recently, other modalities such as transversus abdominis plane (TAP) blocks and wound irrigation (PainBuster®) with local anaesthetic (0.2% ropivacaine®) have shown a reduction in use of opiates and improvement in patient mobilisation in the early post-operative period

Opiates have a profound negative effect on the gut motility, consequently delaying return of gut function and prolonging the duration of POI. Regular use of Paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDS) is recommended unless contraindicated. NSAIDS help promote gut recovery by reducing local mucosal inflammation (Cali, et al. 2000). Prophylactic antiemetics should be prescribed to those patients receiving opiates.

It is emphasised that all patients be allowed oral fluid and diet soon after surgery. Intravenous fluid should be stopped as soon as the patient's oral intake is adequate. There is now evidence to support the view that early commencement of enteral feeding is beneficial and is safe to introduce within 24 hours of surgery (Andersen, et al. 2006; Lewis, et al. 2009). Similarly, early feeding facilitates gut motility and may help in the early return of gut

All patients should have an enforced and structured mobilisation plan during the postoperative period. A designated physiotherapist with a mobilisation plan tailored to the individual patient's need should work closely with the patient in order to achieve best outcome. Early mobilisation is paramount in preventing venous thromboembolism (VTE), respiratory complications and reduction in muscle strength (Schuster and Montie 2002). It is

collection (Jesus, et al. 2004; Karliczek, et al. 2006; Urbach, et al. 1999)**.** 

dependency unit is therfore critical.

function and reduce the ileus.

(Bamigboye and Hofmeyr 2009; Beaussier, et al. 2007).

**4.1.4 Post-operative components of ERAS protocols** 

noteworthy that early post-operative ambulation plays a little role in preventing or resolving POI. However, it has proven benefits in preventing atelectasis, pneumonia and VTE (Carroll and Alavi 2009) which may cause secondary POI.

A clinical management pathway, based on ERAS protocols, is proposed below which would be useful for colorectal surgeons in day-to-day management of surgical patients (Figure- 3).

Fig. 3. Clinical management pathway based on ERAS protocols

### **4.2 Laparoscopic approach**

Introduction of laparoscopic approach has significant imapct on surgical practice, for both the surgeons and patients alike. It is known that the laparoscopic techniques cause less surgical stress and trauma, and the patients recover faster (Bauer and Boeckxstaens 2004; Kalff, et al. 1998). Laparoscopic surgery involves less bowel manipulation and inflicts reduced tissue trauma compared with open approach. Similarly, reduced inflammatory and catabolic responses in laparoscopic approach may also result in early recovery after operation. Therefore, the return of gut function is faster compared to open surgery. Effective postoperative analgesia may be obtained with simple analgesics and use of opiates can easily be avoided. Understandably, laparoscopic technique is considered to reduce severity and duration of ileus resulting in shorther length of stay in hospital (Leung, et al. 2004).

Laparoscopic technique has attracted ethusiasm and application by most surgical specialities and has become standard approach for a number of surgical procedures. Its wide spread popularity is based on the short term benefits. Randomised studies have demonstrated that laparoscopic approach reduces duration of POI after abdominal surgery (Basse, et al. 2003; Lacy, et al. 1995; Milsom, et al. 1998). Similarly, laparoscopic colorectal resections have been shown to cause less post-operative pain, and early return of organ function and discharge from hospital when compared with conventional open surgery (Reza, et al. 2006).

Whereas individual trials demostrate short term benefits of laparoscopic approach especially in early postoperative period (Guillou, et al. 2005; Murray, et al. 2006; Veldkamp, et al. 2005), a Cochrane review found no difference in long term outcomes compared with open approach (Kuhry, et al. 2008). However, it is important to consider that most of above evidence is collected from studies lacking ERAS programme of perioperative optimisation. Recently, two trials investigated impact of laparoscopic approach within ERAS application (Basse, et al. 2005; King, et al. 2006). Unfortunately, the results of these two trials are not consistent. Basse et al. failed to show any advantage of laparoscopic approach in colonic resections, while King et al suggested benefits of laparoscopic approach compared with open techniques. However, latter trial was not blinded which might have impacted on the results of the study. Nevertheless, it is established that laparoscopic surgery, in general, is associated with reduced post operative pain and inflammatory response. Consequently, it may play a role in reducing the incidence of POI (Story and Chamberlain 2009). More work is underway in this area and evidence is eagerly awaited.

### **4.3 Pharmacological therapies**

There are a number of pharmacological therapies which are part of ERAS protocols. For instance, carbohydrate loading, use of NSAID and prophylactic anti-emetics, epidural and/or regional analgesia are integral part of ERAS pathways. These therapeutic modalities have been shown to have significant impact on early return of gut function (Kehlet and Wilmore 2008). Moreover, it is possible to avoid opiates which have a profound effect on gut motility and cause ileus.

A number of new pharmacological agents are under investigation at different levels. For example, Alvimopan, a selective Mu-opioid receptor antagonist which acts peripherally, has been shown to have positive effect on the ileus in phase III trail. It has been shown to have an association with early return of bowel function, reduced incidence of POI, and reduction in length of hospital stay (Ludwig, et al. 2010). Similarly, estimated hospital cost was reduced by \$879 - \$977 for patients who received alvimopan compared with placebo. Longterm safety, accurate indications and dosage are important issues which need addressing before its widespread use in future. However, it is unknown that if alvimopan is more cost effective than optimal use of laparoscopic approach and ERAS protocols, and further research is needed (Stewart and Waxman 2010).

Similarly, vagal stimulation by enteral administration of lipid-rich nutrition has shown early recovery of gut peristalsis (Lubbers, et al. 2010). Other agents such as peripheral opioid antagonist methylnaltrexone, motilin analogue atilmotin and Cisapride have been used with promising results (Livingston and Passaro 1990). Adrenergic blockers and parasympathetic agonists (e.g neostigmine) have also been investigated as potential options in treating POI. Unfortunately, these agents have serious side effects and hence not suitable for routine practice. Moreover, drugs such as Erythromycin and Metoclopramide have shown some favourable results in early gastric emptying, however, there is no quality data to support their routine use at a larger scale in daily practice (Sustic, et al. 2005; Yeo, et al. 1993). A recent review suggested that gum chewing in postoperative period is associated with reduction in POI, likely due to vagal stimulation of the gastrointestinal tract (Fitzgerald and Ahmed 2009).

The pharmacological management of POI is still evolving and has an important role in the management of POI. Further evidence is required to establish the summative effect of pharmacological therapies, laparoscopic surgery and ERAS pathways.

### **5. Conclusion**

46 Contemporary Issues in Colorectal Surgical Practice

Introduction of laparoscopic approach has significant imapct on surgical practice, for both the surgeons and patients alike. It is known that the laparoscopic techniques cause less surgical stress and trauma, and the patients recover faster (Bauer and Boeckxstaens 2004; Kalff, et al. 1998). Laparoscopic surgery involves less bowel manipulation and inflicts reduced tissue trauma compared with open approach. Similarly, reduced inflammatory and catabolic responses in laparoscopic approach may also result in early recovery after operation. Therefore, the return of gut function is faster compared to open surgery. Effective postoperative analgesia may be obtained with simple analgesics and use of opiates can easily be avoided. Understandably, laparoscopic technique is considered to reduce severity and duration of ileus resulting in shorther length of stay in hospital

Laparoscopic technique has attracted ethusiasm and application by most surgical specialities and has become standard approach for a number of surgical procedures. Its wide spread popularity is based on the short term benefits. Randomised studies have demonstrated that laparoscopic approach reduces duration of POI after abdominal surgery (Basse, et al. 2003; Lacy, et al. 1995; Milsom, et al. 1998). Similarly, laparoscopic colorectal resections have been shown to cause less post-operative pain, and early return of organ function and discharge from hospital when compared with conventional open surgery

Whereas individual trials demostrate short term benefits of laparoscopic approach especially in early postoperative period (Guillou, et al. 2005; Murray, et al. 2006; Veldkamp, et al. 2005), a Cochrane review found no difference in long term outcomes compared with open approach (Kuhry, et al. 2008). However, it is important to consider that most of above evidence is collected from studies lacking ERAS programme of perioperative optimisation. Recently, two trials investigated impact of laparoscopic approach within ERAS application (Basse, et al. 2005; King, et al. 2006). Unfortunately, the results of these two trials are not consistent. Basse et al. failed to show any advantage of laparoscopic approach in colonic resections, while King et al suggested benefits of laparoscopic approach compared with open techniques. However, latter trial was not blinded which might have impacted on the results of the study. Nevertheless, it is established that laparoscopic surgery, in general, is associated with reduced post operative pain and inflammatory response. Consequently, it may play a role in reducing the incidence of POI (Story and Chamberlain 2009). More work

There are a number of pharmacological therapies which are part of ERAS protocols. For instance, carbohydrate loading, use of NSAID and prophylactic anti-emetics, epidural and/or regional analgesia are integral part of ERAS pathways. These therapeutic modalities have been shown to have significant impact on early return of gut function (Kehlet and Wilmore 2008). Moreover, it is possible to avoid opiates which have a profound effect on gut

A number of new pharmacological agents are under investigation at different levels. For example, Alvimopan, a selective Mu-opioid receptor antagonist which acts peripherally, has

is underway in this area and evidence is eagerly awaited.

**4.3 Pharmacological therapies** 

motility and cause ileus.

**4.2 Laparoscopic approach** 

(Leung, et al. 2004).

(Reza, et al. 2006).

POI is a complex condition of multifactorial aetiology, most commonly seen following abdominal surgery. It causes significant frustration amongst health professionals and patients alike. It is one of the commonest causes of delay in patients' postoperative recovery and carries financial implications due to prolonged length of stay. It is estimated to cost \$1.28 billion annually in United States (Senagore 2007).

In recent years, efforts have been made to address this issue albeit without any major progress. Nonetheless, our understanding of pathophysiology of ileus is better than before and a number of strategies to overcome the causative factors have been tried (Stewart and Waxman 2010; Story and Chamberlain 2009). Although such strategies help reduce the duration of ileus, they have limited role in preventing its onset (Lubawski and Saclarides 2008). Three major mechanisms – neurogenic, inflammatory and pharmacological – have been implicated in causing ileus (Augestad and Delaney 2010). The level of activation of these factors varies during a surgical procedure. Moreover, understanding of pharmacological mechanisms has opened new windows for research and interventions in this area.

Evidence has accumulated to suggest enhanced recovery after surgery protocol, laparoscopic approach, and pharmacological interventions all reduce the incidence of ileus. Figure 4 illustrates a suggested pathway for prevention and management of prolonged Ileus.

Fig. 4. Management pathway for Prolonged POI

Laparoscopic surgery produces better short term results compared with open approach (Guillou, et al. 2005; Hewett, et al. 2008)**.** Short term morbidity, including incidence of ileus, is significantly low in patients treated with laparoscopic approach. It remains an area of significant reserach interest to investigate whether the combination of laparoscopic surgery and ERAS protocol will offer any further clinical benefit. The ongoing LAFA (Dutch) and EnRoL (UK) trials are desinged to answer above question when completed (Wind, et al. 2006a).

Of above, ERAS pathway was most extensively studied intervention over the last 15 years.The components of ERAS protocol are aimed at optimising patient care, reducing operative stress, and enhancing recovery after surgery by persevering normal physiology and early return of gastrointestinal function. Whereas POI has not been investigated as sole primary endpoint in studies comparing ERAS verusu conventional perioperative care, it has been studied as a part of morbidity rates in both as primary and secondary endpoints. There is now evidence that ERAS protocol of perioperative care is associated with significant reduction in incidence of POI, along with length of hospital stay, compared with conventional perioperative care.

Pharmacological interventions, as part of ERAS or outside ERAS, play key role in reduction of incidence of ileus. Such interventions with promising results include use of preoperative carbohydrate loading, NSAIDs, prophylactic anti-emetics, and epidural and/or regional analgesia. Avoidance of opiates and use of mu-opoid receptor antagonists are associated with early return of gut function.

The impact of ileus as an important health issue cannot be over emphasized:

*"In patients who underwent colectomy surgery, postoperative ileus was associated with a 29% increase in hospital LOS and a 15% increase in hospitalization costs. Prevention of postoperative ileus could potentially yield benefits in reduction in hospital LOS and associated health care costs."*  (Lyer, et al. 2009)

POI is a challenging yet preventable event in surgical patients. It has a multifactorial pathophysiology that requires a multimodal approach in its management. Whereas there is no definitive treatment of ileus, strategies to prevent and manage ileus should be followed as discussed above. Essentially, prevention and management of POI centres on minimising perioperative stress and preserving normal physiological functions.

### **6. References**

48 Contemporary Issues in Colorectal Surgical Practice

Post Operative Ileus Prevention and clinical management pathway

Prevention of POI Management of Prolonged POI

Perioperative optimisation Mechanical obstruction must be

Nutritional support

Prevention of complications such as chest infection, heart failure , urinary infection , intrabdominal sepsis

Fig. 4. Management pathway for Prolonged POI

approach

therapy

Implementation of ERAS protocols

Use of minimally invasive surgical

Consider use of pharmacological

excluded with contrast studies

watchful waiting and supportive treatment

Nil per mouth

Intravenous fluids

, reduce opiates use

Consider nasogastric tube

Correct electrolytes imbalance

Treat underlying cause i.e. sepsis

Patient developing gut failure consider artificial nutrition through central line

2004 A comparison of laparoscopically assisted and open colectomy for colon cancer. N Engl J Med 350(20):2050-9.


Augestad, K. M., and C. P. Delaney 2010 Postoperative ileus: impact of pharmacological

Bamigboye, A. A., and G. J. Hofmeyr 2009 Local anaesthetic wound infiltration and

Barquist, E., et al. 1996 Neuronal pathways involved in abdominal surgery-induced gastric

Basse, L., et al. 2005 Functional recovery after open versus laparoscopic colonic resection: a

— 2003 Gastrointestinal transit after laparoscopic versus open colonic resection. Surg

Bauer, A. J., and G. E. Boeckxstaens 2004 Mechanisms of postoperative ileus.

Bauer, A. J., M. G. Sarr, and J. H. Szurszewski 1991 Opioids inhibit neuromuscular

Bauer AJ, Szurszewski JH. 1991 Effect of opioid peptides on circular muscle of canine

Beaussier, M., et al. 2007 Continuous preperitoneal infusion of ropivacaine provides

Boeckxstaens, G. E., et al. 1999 Activation of an adrenergic and vagally-mediated NANC

— 2000 Evidence for VIP(1)/PACAP receptors in the afferent pathway mediating surgery-

Bonaz, B., and Y. Tache 1997 Corticotropin-releasing factor and systemic capsaicin-sensitive

Carroll, J., and K. Alavi 2009 Pathogenesis and management of postoperative ileus. Clin

Cicalese, L., et al. 1996 Pyruvate prevents mucosal reperfusion injury, oxygen free-radical

Cochrane, J. P., et al. 1981 Arginine vasopressin release following surgical operations. Br J

de Jonge, W. J., et al. 2003 Postoperative ileus is maintained by intestinal immune infiltrates that activate inhibitory neural pathways in mice. Gastroenterology 125(4):1137-47. De Winter, B. Y., et al. 1997 Effect of adrenergic and nitrergic blockade on experimental ileus

— 1998 Role of VIP1/PACAP receptors in postoperative ileus in rats. Br J Pharmacol

paraventricular nucleus of the hypothalamus. Brain Res 748(1-2):12-20. Cali, R. L., et al. 2000 Effect of Morphine and incision length on bowel function after

induced fundic relaxation in the rat. Br J Pharmacol 131(4):705-10.

double-blind, placebo-controlled study. Anesthesiology 107(3):461-8. Boeckxstaens, G. E., and W. J. de Jonge 2009 Neuroimmune mechanisms in postoperative

transmission in circular muscle of human and baboon jejunum. Gastroenterology

effective analgesia and accelerates recovery after colorectal surgery: a randomized,

pathway in surgery-induced fundic relaxation in the rat. Neurogastroenterol Motil

afferents are involved in abdominal surgery-induced Fos expression in the

production, and neutrophil infiltration after rat small bowel preservation and

Gastroenterol 16(17):2067-74.

Endosc 17(12):1919-22.

ileus. Gut 58(9):1300-11.

101(4):970-6.

11(6):467-74.

Cochrane Database Syst Rev (3):CD006954.

Neurogastroenterol Motil 16 Suppl 2:54-60.

colectomy. Dis Colon Rectum 43(2):163-8.

transplantation. Transplant Proc 28(5):2611.

in rats. Br J Pharmacol 120(3):464-8.

Colon Rectal Surg 22(1):47-50.

Surg 68(3):209-13.

124(6):1181-6.

duodenum j Physiol 434:409- 422.

ileus in rats. Am J Physiol 270(4 Pt 2):R888-94.

randomized, blinded study. Ann Surg 241(3):416-23.

treatment, laparoscopic surgery and enhanced recovery pathways. World J

abdominal nerves block during caesarean section for postoperative pain relief.


Kalff, J. C., Schraut WH, Billiar TR, Simmons RL, Baur AJ, 1999 Roles of inducible nitric

Karliczek, A., et al. 2006 Drainage or nondrainage in elective colorectal anastomosis: a

Kehlet, H., and D. W. Wilmore 2008 Evidence-based surgical care and the evolution of fast-

Khoo, C. K., et al. 2007 A prospective randomized controlled trial of multimodal

King, P. M., et al. 2006 Randomized clinical trial comparing laparoscopic and open surgery for colorectal cancer within an enhanced recovery programme. Br J Surg 93(3):300-8. Kubes, P., and S. Kanwar 1994 Histamine induces leukocyte rolling in post-capillary

Kuhry, E., et al. 2008 Long-term results of laparoscopic colorectal cancer resection. Cochrane

Kurz, A., and D. I. Sessler 2003 Opioid-induced bowel dysfunction: pathophysiology and

Lacy, A. M., et al. 1995 Short-term outcome analysis of a randomized study comparing laparoscopic vs open colectomy for colon cancer. Surg Endosc 9(10):1101-5. Leung, K. L., et al. 2004 Laparoscopic resection of rectosigmoid carcinoma: prospective

Lewis, S. J., H. K. Andersen, and S. Thomas 2009 Early enteral nutrition within 24 h of

Lindwall, R., et al. 1998 Forced air warming and intraoperative hypothermia. Eur J Surg

Lubawski, J., and T. Saclarides 2008 Postoperative ileus: strategies for reduction. Ther Clin

Lubbers, T., W. Buurman, and M. Luyer 2010 Controlling postoperative ileus by vagal

Luckey, A., E. Livingston, and Y. Tache 2003 Mechanisms and treatment of postoperative

Ludwig, K., et al. 2010 Alvimopan for the management of postoperative ileus after bowel

Marret, E., C. Remy, and F. Bonnet 2007 Meta-analysis of epidural analgesia versus parenteral opioid analgesia after colorectal surgery. Br J Surg 94(6):665-73. Mattei, P., and J. L. Rombeau 2006 Review of the pathophysiology and management of

Melling, A. C., et al. 2001 Effects of preoperative warming on the incidence of wound

Miedema, B. W., and J. O. Johnson 2003 Methods for decreasing postoperative gut

Livingston, E. H., and E. P. Passaro, Jr. 1990 Postoperative ileus. Dig Dis Sci 35(1):121-32. Lobo, D. N., et al. 2002 Effect of salt and water balance on recovery of gastrointestinal

intestinal surgery versus later commencement of feeding: a systematic review and

function after elective colonic resection: a randomised controlled trial. Lancet

resection: characterization of clinical benefit by pooled responder analysis. World J

infection after clean surgery: a randomised controlled trial. Lancet 358(9285):876-80.

systematic review and meta-analysis. Colorectal Dis 8(4):259-65.

venules. A P-selectin-mediated event. J Immunol 152(7):3570-7.

Gastroenterology 188:316-27.

track surgery. Ann Surg 248(2):189-98.

Database Syst Rev (2):CD003432.

164(1):13-6.

359(9320):1812-8.

Surg 34(9):2185-90.

Risk Manag 4(5):913-7.

ileus. Arch Surg 138(2):206-14.

resection for cancer. Ann Surg 245(6):867-72.

potential new therapies. Drugs 63(7):649-71.

randomised trial. Lancet 363(9416):1187-92.

meta-analysis. J Gastrointest Surg 13(3):569-75.

activation. World J Gastroenterol 16(14):1683-7.

postoperative ileus. World J Surg 30(8):1382-91.

dysmotility. Lancet Oncol 4(6):365-72.

oxide synthase in postoperative intestinal smooth muscle dysfunction in rodents. .

perioperative management protocol in patients undergoing elective colorectal


**Part 2** 

**Laparoscopic Colorectal Surgery** 

54 Contemporary Issues in Colorectal Surgical Practice

Smith, J., K. A. Kelly, and R. M. Weinshilboum 1977 Pathophysiology of postoperative ileus.

Soop, M., et al. 2004 Preoperative oral carbohydrate treatment attenuates endogenous

Story, S. K., and R. S. Chamberlain. 2009 A comprehensive review of evidence-based strategies to prevent and treat postoperative ileus. Dig Surg 26(4):265-75. Sustic, A., et al.2005 Metoclopramide improves gastric but not gallbladder emptying in

Svanfeldt, M., et al. 2007 Randomized clinical trial of the effect of preoperative oral

Tache, Y., et al. 1993 Role of CRF in stress-related alterations of gastric and colonic motor

Takegami, K., et al. 2003 Minilaparotomy approach to colon cancer. Surg Today 33(6):414-20. Urbach, D. R., E. D. Kennedy, and M. M. Cohen 1999 Colon and rectal anastomoses do not

Varadhan, K. K., et al. 2010 The enhanced recovery after surgery (ERAS) pathway for

Veldkamp, R., et al. 2005 Laparoscopic surgery versus open surgery for colon cancer: short-

Weiskopf, R. B., et al. 1987 Effects of fentanyl on vasopressin secretion in human subjects. J

Werawatganon, T., and S. Charuluxanun 2005 Patient controlled intravenous opioid

Wershil, B. K., et al. 1996 Mast cell-dependent neutrophil and mononuclear cell recruitment

Wille-Jorgensen, P., et al. 2003 Heparins and mechanical methods for thromboprophylaxis in

Wind, J., et al. 2006a Perioperative strategy in colonic surgery; LAparoscopy and/or FAst track multimodal management versus standard care (LAFA trial). BMC Surg 6:16. — 2006b Systematic review of enhanced recovery programmes in colonic surgery. Br J Surg

Wong, P. F., et al. 2007 Randomized clinical trial of perioperative systemic warming in major

Wood, J. D. 2008 Enteric nervous system: reflexes, pattern generators and motility. Curr

Yeo, C. J., et al. 1993 Erythromycin accelerates gastric emptying after pancreaticoduo-

denectomy. A prospective, randomized, placebo-controlled trial. Ann Surg 218(3):

cardiac surgery patients with early intragastric enteral feeding: randomized

carbohydrate treatment on postoperative whole-body protein and glucose kinetics.

require routine drainage: a systematic review and meta-analysis. Ann Surg

patients undergoing major elective open colorectal surgery: a meta-analysis of

analgesia versus continuous epidural analgesia for pain after intra-abdominal

in immunoglobulin E-induced gastric reactions in mice. Gastroenterology

glucose release 3 days after surgery. Clin Nutr 23(4):733-41.

2010 Management of postoperative ileus. Dis Mon 56(4):204-14.

controlled trial. Croat Med J 46(2):239-44.

function. Ann N Y Acad Sci 697:233-43.

Pharmacol Exp Ther 242(3):970-3.

randomized controlled trials. Clin Nutr 29(4):434-40.

surgery. Cochrane Database Syst Rev (1):CD004088.

elective abdominal surgery. Br J Surg 94(4):421-6.

Opin Gastroenterol 24(2):149-58.

229-37; discussion 237-8.

term outcomes of a randomised trial. Lancet Oncol 6(7):477-84.

colorectal surgery. Cochrane Database Syst Rev (4):CD001217.

Arch Surg 112(2):203-9.

Br J Surg 94(11):1342-50.

229(2):174-80.

110(5):1482-90.

93(7):800-9.

Stewart, D., and K. Waxman

### **Laparoscopic Surgery for Rectal Cancer: Approaches, Challenges and Outcome**

Emad H. Aly *Aberdeen Royal Infirmary, Scotland United Kingdom* 

### **1. Introduction**

Jacobs et al (1991) reported the first series of laparoscopic colonic resections in 20 patients. It took over a decade of debate and controversy to establish that laparoscopic colon surgery for cancer, when compared with open surgery, is associated with better short term outcomes while maintaining at least equivalent long-term outcomes (Lee, 2009). These improved short term outcomes include reduced postoperative pain, short hospital stay, decreased intraoperative blood loss, quicker return of gut function and faster return to normal activities (Lacey et al., 2002; Veldkamp et al. ; 2005, Guillou et al., 2005). However, the debate around laparoscopic rectal surgery is far from over.

Oncologic outcomes of rectal cancer patients have been shown to depend on the skills and techniques of the operating surgeon (Heald et al., 1998). It took the surgical community several years to accept and adopt the current modern concepts of rectal cancer surgery which involves the standardisation of surgical resection with total mesorectal excision (Heald et al; 1986) and adequate circumferential resection margin (Quirke et al., 1988). It seems that the surgical community has yet to go through another phase of development in the surgical management of rectal cancer to address the concerns whether the technical challenges of laparoscopy may further add to the complexity of the surgical technique that may result in variability in outcomes (Lee, 2009).

Even though there are several studies on the outcomes of laparoscopic rectal surgery, there is limited level 1 evidence in surgical literature (Kang et al., 2010). Safety and benefits associated with laparoscopic colon cancer surgery have been demonstrated in many prospective randomized trials. However the same benefits have not yet been clearly confirmed for laparoscopic rectal cancer surgery (Lee, 2009). The debate around laparoscopic rectal surgery has become even more complex with the slow, but steady, increase of the practice of robotic rectal surgery. To be universally accepted, minimally invasive approaches to rectal cancer need to demonstrate at least equivalent onlcologic & safety results to open surgery combined with evidence of improved short term outcomes. In addition, minimally invasive approach should be cost-effective (Champagne et al., 2007).

### **2. Conventional laparoscopic rectal surgery**

### **2.1 Pros and cons of conventional laparoscopic rectal surgery**

Laparoscopic surgery provides unique, unobstructed views of the rectal dissection not only for the operating surgeon but also to the entire surgical team. Magnification of the surgical field allows more precise dissection. The pneumoperitoneum assists in opening up the planes for mobilization of the mesorectum (Lee, 2009). Also, blood loss is minimised as meticulous haemostasis is essential to preserve the laparoscopic view. (Cecil et al., 2006).

However, there are many well documented limitations to conventional laparoscopic rectal surgery. These include tremor, assistant dependant unstable two-dimensional view, inability to perform high-precision suturing, poor ergonomics and fixed tips as well as limited dexitry of surgical instruments (Delaney et al., 2003; Choi et al., 2009; Abodeely et al, 2010). These limitations are particularly relevant for rectal cancer surgery. As the surgeon operates into the confines of the pelvis the dissection becomes more difficult due to a combination of factors. Retraction of the rectum may prove difficult as one approaches the retrorectal and Denovillier's fascias. Crowding and clashing of instruments can result in a poor view and an experienced assistant is essential. Diathermy or vapour fumes from energy sources in the confined spaces of the pelvis often results in fogging of the camera scope that could slow progress of the procedure (Cecil et al., 2006).

### **2.2 Challenges in conventional laparoscopic rectal surgery**

There are many technical challenges that are associated with laparoscopic rectal cancer surgery. One of the main technical challenges is obtaining adequate exposure, tissue tension & retraction of the rectum by the currently available conventional laparoscopic instruments. In the absence of tactile feedback during laparoscopic surgery, intra-operative localisation of the tumour represents another challenge. Lesions during laparoscopic colon surgery are easily identifiable with or without tattoo marks. However, this is not easily possible with rectal cancers without tactile feedback. It is often difficult to determine the extent of distal rectal dissection that is needed to grantee adequate tumour clearance and to be sure that the stapler is applied at the appropriate level distal to the tumour (Lee, 2009).

There are well known limitations in the currently available laparoscopic distal rectal stapling devices. Most of the current laparoscopic staplers can only reticulate to a maximum of 65 degrees which makes horizontal division of the rectum difficult. For this reason, multiple firings are often required to complete distal rectal transection (Cecil et al., 2006). Division of the rectum in the presence of very low anterior and bulky lesions is particularly challenging (Champagne et al., 2011). Laparoscopic division of the distal rectum is not always technically feasible because of the limited angulation of the stapling device and the physical limitations of working in the bony confines of the pelvis. A virtual simulation demonstrated that the current design of staplers has to go through the iliac bone in order to achieve a 90° angle at the level of levator ani (Brannigan et al., 2006). Some surgeons overcome by this by the use of a conventional stapler through a small suprapubic incision (Shalli et al., 2009).

Identifying the correct surgical plane anterior to Denonvillier's fascia during conventional laparoscopic rectal surgery, adequate radial margin and maintaining meticulous haemostasis are essential for high quality rectal cancer surgery. This can be challenging as without adequate retraction and tissue tension, surgical planes can be more ambiguous. Any bleeding will further obscure the appropriate anatomy (Champagne et al., 2011).

### **2.3 Outcomes of conventional laparoscopic rectal surgery**

### **2.3.1 Evidence from early randomised controlled trials**

58 Contemporary Issues in Colorectal Surgical Practice

Laparoscopic surgery provides unique, unobstructed views of the rectal dissection not only for the operating surgeon but also to the entire surgical team. Magnification of the surgical field allows more precise dissection. The pneumoperitoneum assists in opening up the planes for mobilization of the mesorectum (Lee, 2009). Also, blood loss is minimised as meticulous haemostasis is essential to preserve the laparoscopic view. (Cecil et al., 2006).

However, there are many well documented limitations to conventional laparoscopic rectal surgery. These include tremor, assistant dependant unstable two-dimensional view, inability to perform high-precision suturing, poor ergonomics and fixed tips as well as limited dexitry of surgical instruments (Delaney et al., 2003; Choi et al., 2009; Abodeely et al, 2010). These limitations are particularly relevant for rectal cancer surgery. As the surgeon operates into the confines of the pelvis the dissection becomes more difficult due to a combination of factors. Retraction of the rectum may prove difficult as one approaches the retrorectal and Denovillier's fascias. Crowding and clashing of instruments can result in a poor view and an experienced assistant is essential. Diathermy or vapour fumes from energy sources in the confined spaces of the pelvis often results in fogging of the camera

There are many technical challenges that are associated with laparoscopic rectal cancer surgery. One of the main technical challenges is obtaining adequate exposure, tissue tension & retraction of the rectum by the currently available conventional laparoscopic instruments. In the absence of tactile feedback during laparoscopic surgery, intra-operative localisation of the tumour represents another challenge. Lesions during laparoscopic colon surgery are easily identifiable with or without tattoo marks. However, this is not easily possible with rectal cancers without tactile feedback. It is often difficult to determine the extent of distal rectal dissection that is needed to grantee adequate tumour clearance and to be sure that the

There are well known limitations in the currently available laparoscopic distal rectal stapling devices. Most of the current laparoscopic staplers can only reticulate to a maximum of 65 degrees which makes horizontal division of the rectum difficult. For this reason, multiple firings are often required to complete distal rectal transection (Cecil et al., 2006). Division of the rectum in the presence of very low anterior and bulky lesions is particularly challenging (Champagne et al., 2011). Laparoscopic division of the distal rectum is not always technically feasible because of the limited angulation of the stapling device and the physical limitations of working in the bony confines of the pelvis. A virtual simulation demonstrated that the current design of staplers has to go through the iliac bone in order to achieve a 90° angle at the level of levator ani (Brannigan et al., 2006). Some surgeons overcome by this by the use of a conventional stapler through a small

Identifying the correct surgical plane anterior to Denonvillier's fascia during conventional laparoscopic rectal surgery, adequate radial margin and maintaining meticulous

**2. Conventional laparoscopic rectal surgery** 

**2.1 Pros and cons of conventional laparoscopic rectal surgery** 

scope that could slow progress of the procedure (Cecil et al., 2006).

stapler is applied at the appropriate level distal to the tumour (Lee, 2009).

suprapubic incision (Shalli et al., 2009).

**2.2 Challenges in conventional laparoscopic rectal surgery** 

The MRC CLASICC (**C**onventional vs. **L**aparoscopic- **A**ssisted **S**urgery in **C**olorectal **C**ancer) Trial was done between 1996 and 2002 in 27 UK centres. It randomised 794 patients with colon and rectal cancer into laparoscopic resection (n = 526) open resection (n = 268) with a ratio of 2:1. The CLASICC trial was the first RCT to include patients with rectal cancer. The study reported a 29% conversion rate. Patients who had conversion ended up with increased complication rates. Also, there was higher incidence of positive circumferential resection margin after laparoscopic anterior resection but this did not reach statistical significance. There was no difference in hospital mortality or quality of life at 2 weeks and 3 months postoperatively (Guillou et al., 2005).

A subset of 148 patients in the CLASICC trial was analyzed with regard to sexual and urinary function with the help of validated questionnaires. The perceived change in the overall level of sexual function was considerably higher in the laparoscopic group compared with the conventional group (41 vs 23%). These differences in sexual function reflected a clear trend, but were not significant at the 5% level.

Multivariate analysis revealed that conversion to open surgery was significantly correlated with postoperative male sexual dysfunction. In this study morbidity was an obvious issue in rectal surgery. Therefore, the authors concluded: *'laparoscopic resection for colon cancer is as effective as open surgery. However, impaired short-term outcomes after laparoscopic resection for rectal cancer do not yet justify its routine use. '* (Guillou et al., 2005).

### **2.3.2 Challenges in rectal surgery as identified from the clasicc trial**

The outcomes of the MRC CLASICC trial should be interpreted with caution as in the study design, which was based on the best available data at that time (Simons et al., 1995), the surgeons' learning curve was set at 20 laparoscopic resections. Clearly this was an underestimation of the learning curve especially for rectal surgery (Leung et al., 2004; Good et al., 2011). This could explain the increased complication rate for laparoscopic rectal resections in the study and the authors' conclusion that laparoscopic rectal surgery was associated with increased morbidity. The reduction in the conversion rates for every year of the study is an indication that the learning curve was operative during the trial (Guillou et al, 2005). More recent studies set the learning curve at 55 cases for right-sided and 62 for leftsided laparoscopic colonic resections to achieve proficiency (Tekkis et al., 2005). However, there is little data on the numbers required to achieve proficiency in laparoscopic rectal cancer surgery (Good et al., 2011).

Despite the limitations of the MRC CLASICC trial, it helped to highlight the challenges of laparoscopic rectal surgery when compared to laparoscopic colon surgery. These findings were confirmed & debated in other publications (Quah et al., 2002; Scheidbach et al., 2002; Cecil et al., 2006). It became evident that laparoscopic rectal surgery has a longer learning curve & higher conversion rate, increased circumferential margin involvement as well as poorer outcome of urinary and sexual function especially in men (Quah et al., 2002; Bretagnol et al., 2005).

Increased anastomotic leak rate was another challenge that was identified in laparoscopic rectal surgery. Multiple firings are often required to complete distal rectal transection as the current laparoscopic staplers can only reticulate to a maximum of 65 degrees and therefore horizontal division of the rectum difficult. This is even more challenging for low-lying lesions and may contribute to increased anastomotic leakage. There is a documented positive relationship between the number of linear endostapler firings and anastomotic leak rate (Ito et al., 2008; Kim et al., 2009). Reported leak rate of 17% if the anastomosis were located less than 12 cm from the anal verge and as high as 25% in those patients who were not diverted following laparoscopic rectal surgery (Morino et al., 2003). These leak rates are higher than those reported after open rectal resection (4–11%) (Enker et al., 1995; Heald et al. 1998). Refinements in the laparoscopic stapling devices may help addressing this problem in the future.

### **2.3.3 Evidence from more recent publications**

More recent publications show much lower rate of circumferential resection margin (CRM) involvement following conventional laparoscopic rectal surgery between 2. 14%-4% (Ng K. H. et al., 2009; Lujan et al., 2009; Ng SS et al., 2009). On the other hand, anastomotic leak rate remains high for most of the studies in the range of 9 to 17% compared to 5% for open surgery (Champagne et al., 2007). However, some authors report anastomotic leak rate after conventional laparoscopic rectal surgery as low as 3. 8% (Good et al., 2011).

### **2.3.4 Evidence from meta-analysis and cochrane reviews**

The CRM involvement was evaluated in a meta-analysis of 10 trials reported a mean positive radial margin of 5% for laparoscopic resections compared with 8% for open resections. However, this was not statistically significant. The distal margin positivity rates were also not different between laparoscopic and open rectal surgery (Anderson et al., 2008). However, it should be noted that a clear distal margin can be of an issue in laparoscopic resections of the lower third of the rectum, especially in male patients (Laurent et al., 2007).

A meta-analysis for 20 studies published between 1993 and 2004 looking at laparoscopic versus open surgery for rectal cancer showed that there was no significant difference in circumferential margin positivity or number of lymph nodes harvested. This confirmed that laparoscopic and open surgery were comparable in terms of their adequacy of oncological clearance (Aziz et al., 2006). Despite the known limitations of meta-analysis of nonrandomized data, the authors' conclusions are particularly useful because of the limited number of randomized data available for laparoscopic rectal cancer surgery (Champagne et al., 2007).

A Cochran systematic review for 48 studies comparing laparoscopic and open resection for rectal cancer concluded that laparoscopic TME surgery had clinically measurable short-term advantages in patients with primary resectable rectal cancer (Breukink et al., 2006).

### **2.3.5 Outcomes of conventional laparoscopic resection of extra-peritoneal rectal cancer in recent studies**

The ongoing debate as to the exact length of the rectum makes it difficult to accurately assess the results of the various studies reporting the outcomes of laparoscopic rectal surgery. Despite these apparent discrepancies there is an agreement that rectal cancer consists of extra-peritoneal and intra-peritoneal lesions and those tumours at or below the peritoneal reflection ideally should be grouped together (Champagne et al., 2011) when discussing laparoscopic rectal cancer outcomes because those lesions represent the real challenge for conventional laparoscopic rectal surgery. There is only limited number of studies that specifically address short and long term outcomes of conventional laparoscopic resection of these lesions.

### **Short-term Outcomes:**

60 Contemporary Issues in Colorectal Surgical Practice

curve & higher conversion rate, increased circumferential margin involvement as well as poorer outcome of urinary and sexual function especially in men (Quah et al., 2002;

Increased anastomotic leak rate was another challenge that was identified in laparoscopic rectal surgery. Multiple firings are often required to complete distal rectal transection as the current laparoscopic staplers can only reticulate to a maximum of 65 degrees and therefore horizontal division of the rectum difficult. This is even more challenging for low-lying lesions and may contribute to increased anastomotic leakage. There is a documented positive relationship between the number of linear endostapler firings and anastomotic leak rate (Ito et al., 2008; Kim et al., 2009). Reported leak rate of 17% if the anastomosis were located less than 12 cm from the anal verge and as high as 25% in those patients who were not diverted following laparoscopic rectal surgery (Morino et al., 2003). These leak rates are higher than those reported after open rectal resection (4–11%) (Enker et al., 1995; Heald et al. 1998). Refinements in the laparoscopic stapling devices may help addressing this problem in

More recent publications show much lower rate of circumferential resection margin (CRM) involvement following conventional laparoscopic rectal surgery between 2. 14%-4% (Ng K. H. et al., 2009; Lujan et al., 2009; Ng SS et al., 2009). On the other hand, anastomotic leak rate remains high for most of the studies in the range of 9 to 17% compared to 5% for open surgery (Champagne et al., 2007). However, some authors report anastomotic leak rate after

The CRM involvement was evaluated in a meta-analysis of 10 trials reported a mean positive radial margin of 5% for laparoscopic resections compared with 8% for open resections. However, this was not statistically significant. The distal margin positivity rates were also not different between laparoscopic and open rectal surgery (Anderson et al., 2008). However, it should be noted that a clear distal margin can be of an issue in laparoscopic resections of the lower third of the rectum, especially in male patients (Laurent et al., 2007). A meta-analysis for 20 studies published between 1993 and 2004 looking at laparoscopic versus open surgery for rectal cancer showed that there was no significant difference in circumferential margin positivity or number of lymph nodes harvested. This confirmed that laparoscopic and open surgery were comparable in terms of their adequacy of oncological clearance (Aziz et al., 2006). Despite the known limitations of meta-analysis of nonrandomized data, the authors' conclusions are particularly useful because of the limited number of randomized data available for laparoscopic rectal cancer surgery

A Cochran systematic review for 48 studies comparing laparoscopic and open resection for rectal cancer concluded that laparoscopic TME surgery had clinically measurable short-term

advantages in patients with primary resectable rectal cancer (Breukink et al., 2006).

conventional laparoscopic rectal surgery as low as 3. 8% (Good et al., 2011).

**2.3.4 Evidence from meta-analysis and cochrane reviews** 

Bretagnol et al., 2005).

the future.

(Champagne et al., 2007).

**2.3.3 Evidence from more recent publications** 

*COREAN Trial (Comparison of Open versus laparoscopic surgery for mid and low REctal cancer After Neoadjuvant chemoradiotherapy)* 

This randomised study by Kang et al. (2010) aimed to evaluate the safety and short-term efficacy of laparoscopic surgery for rectal cancer after preoperative chemoradiotherapy. It was done between 2006-2009 in three tertiary referral centres by teams who have extensive experience in open and laparoscopic rectal surgery. Short-term outcomes assessed were involvement of the circumferential resection margin, macroscopic quality of the total mesorectal excision specimen, number of harvested lymph nodes, recovery of bowel function, perioperative morbidity, postoperative pain, and quality of life. Patients were followed up to assess the 3-year disease-free survival.

Conversion rate was 1. 2%. Laparoscopic group had a longer operating time but less postoperative pain, decreased blood loss and better physical functioning score. There was no difference between the two groups in the involvement of the circumferential resection margin, macroscopic quality of the total mesorectal excision specimen, number of harvested lymph nodes, and peri-operative morbidity did not differ between the two groups. The authors concluded that *'Laparoscopic surgery after preoperative chemoradiotherapy for mid or low rectal cancer is safe and has short-term benefits compared with open surgery; the quality of oncological resection was equivalent'* (Kang et al., 2010).

Even though the COREAN study showed no statistical difference in the anastomotic leak rate between the open and laparoscopic groups, other recent studies have highlighted that laparoscopic resection of extraperitoneal rectal cancer is associated with increased anastomotic leak rate when compared to open surgery. Reported anastomotic leak rate following conventional laparoscopic low anterior resection is 9% (Morino et al., 2003; zhu et al., 2010) and up to 43% for an ultralow anterior resection (Choi et al., 2010).

#### **Long-term Outcomes:**

There is limited number of studies looking at the long-term prognosis following laparoscopic surgical resection of middle and lower rectal cancers. The long term outcomes in this subgroup of patients remain unclear because they are affected by anatomical factors as well as the complexity of the surgical procedures. Li et al. (2011) reported the outcome of 236 patients (laparoscopic, n = 113; open, n = 123) who underwent curative resection for middle and lower rectal cancer from 2000 to 2005. Surgery was performed by the same surgical team with extensive experience in laparoscopic and open procedures. The mean follow-up time of all patients was 74. 8 months. There was no statistical differences in local recurrence, distant recurrence or the 5-year overall survival rates between the laparoscopic and open groups. The authors concluded that *'laparoscopic and open surgery for middle and lower rectal cancer offer similar long-term outcomes. The continued use of laparoscopic surgery in these patients can be supported'*.

### **3. Hybrid and hand-assisted laparoscopic rectal surgery**

In an attempt to avoid compromising oncologic rectal dissection but at the same time maintain the benefits of laparoscopic surgery some have studies reported the use of hybrid procedures in which colonic portion of the surgery is completed by the laparoscopic approach but rectal dissection is completed through a limited low midline or Pfannenstiel incision (Vithiananthan et al., 2001; Shalli et al., 2009).

Similarly, hand-assisted laparoscopic techniques have been used for rectal cancer surgery. Rectal exposure and dissection can be either performed directly through the hand assisted port incision using the open approach following laparoscopic mobilisation of the colon or laparoscopically with manual assistance. The latter technique uses the benefits of the unmatched laparoscopic view and at the same time allow the completion of oncologically similar dissection under tension as in open surgery (Lee et al., 2007).

Hybrid laparoscopic surgery allows the preservation of tactile sensation; optimal traction and exposure of the surgical planes and at the same time helps tumour localization which is a well known challenge in purely laparoscopic approach. Outcomes with this technique have been reported to be favourable and it certainly has some advantages but many surgeons feel that it is not 'totally' laparoscopic rectal surgery and it should not be included in trials or case series for laparoscopic rectal resection. However, the published literature highlights its role and it is suggested that if this procedure continues to demonstrate favourable outcomes and has a shorter learning curve it may require its own procedure code in the future (Champagne et al., 2011).

### **4. Robotic assisted rectal surgery**

The inherent limitations of conventional laparoscopic surgery; which include tremor, unstable two-dimensional view, and limited degree of freedom of the instruments, are particularly significant in patients undergoing rectal cancer surgery with total mesorectal excision (Ballantyne, 2002). Robotic surgery has the potential to address some of these limitations and the potential to offer technical abilities greater than those offered by open or conventional laparoscopic surgery. Robotic colorectal surgery was first reported in by Ballantyne et al. in 2001. The concept of robotic total mesorectal excision for rectal cancer was first reported by Pigazzi et al. in 2006.

### **4.1 Potential advantages of robotic surgery**

Robotic systems can address many of the inherent limitations of conventional laparoscopic surgery. These include the fulcrum effect, poor depth perception, limited range of motion as wells as instrument tremor (Maeso et al., 2010). The use of robotic systems in rectal cancer

surgical team with extensive experience in laparoscopic and open procedures. The mean follow-up time of all patients was 74. 8 months. There was no statistical differences in local recurrence, distant recurrence or the 5-year overall survival rates between the laparoscopic and open groups. The authors concluded that *'laparoscopic and open surgery for middle and lower rectal cancer offer similar long-term outcomes. The continued use of laparoscopic surgery in* 

In an attempt to avoid compromising oncologic rectal dissection but at the same time maintain the benefits of laparoscopic surgery some have studies reported the use of hybrid procedures in which colonic portion of the surgery is completed by the laparoscopic approach but rectal dissection is completed through a limited low midline or Pfannenstiel

Similarly, hand-assisted laparoscopic techniques have been used for rectal cancer surgery. Rectal exposure and dissection can be either performed directly through the hand assisted port incision using the open approach following laparoscopic mobilisation of the colon or laparoscopically with manual assistance. The latter technique uses the benefits of the unmatched laparoscopic view and at the same time allow the completion of oncologically

Hybrid laparoscopic surgery allows the preservation of tactile sensation; optimal traction and exposure of the surgical planes and at the same time helps tumour localization which is a well known challenge in purely laparoscopic approach. Outcomes with this technique have been reported to be favourable and it certainly has some advantages but many surgeons feel that it is not 'totally' laparoscopic rectal surgery and it should not be included in trials or case series for laparoscopic rectal resection. However, the published literature highlights its role and it is suggested that if this procedure continues to demonstrate favourable outcomes and has a shorter learning curve it may require its own procedure code

The inherent limitations of conventional laparoscopic surgery; which include tremor, unstable two-dimensional view, and limited degree of freedom of the instruments, are particularly significant in patients undergoing rectal cancer surgery with total mesorectal excision (Ballantyne, 2002). Robotic surgery has the potential to address some of these limitations and the potential to offer technical abilities greater than those offered by open or conventional laparoscopic surgery. Robotic colorectal surgery was first reported in by Ballantyne et al. in 2001. The concept of robotic total mesorectal excision for rectal cancer

Robotic systems can address many of the inherent limitations of conventional laparoscopic surgery. These include the fulcrum effect, poor depth perception, limited range of motion as wells as instrument tremor (Maeso et al., 2010). The use of robotic systems in rectal cancer

**3. Hybrid and hand-assisted laparoscopic rectal surgery** 

similar dissection under tension as in open surgery (Lee et al., 2007).

incision (Vithiananthan et al., 2001; Shalli et al., 2009).

in the future (Champagne et al., 2011).

**4. Robotic assisted rectal surgery** 

was first reported by Pigazzi et al. in 2006.

**4.1 Potential advantages of robotic surgery** 

*these patients can be supported'*.

surgery has the potential to offer accurate dissection in the avascular 'holly' plane of the rectum without injury to the integrity of the mesorectum or autonomic pelvic nerves in the narrow pelvic cavity. Ultralow rectal dissection could be more easily performed by using precise movements of robotic arms (Kim & Kang, 2010).

Robotic system offers a camera system that is controlled by the operating surgeon combined with three dimensional ten-fold magnification vision thus allowing a perfectly still visibility of the operative field. (Ballantyne & Moll, 2003; Lanfranco et al., 2004; Baik, 2008). One of the main advantages of the use of robotic system in rectal surgery is that it gives the surgeon equal access to both right and left pelvis as if standing above the head of the patient (Hellan et al., 2007). The tips of the instruments of a robotic arm have an endowrist which has functions of seven degrees of freedom, one hundred and eighty degrees articulation and five hundred and forty degrees rotation (Baik, 2008). Also the availability of multi-articulated instruments allows for a range of angles to approach the rectum thus allowing sharp dissection around the rectum and mesorectum. The robotic handles transfer the hand movements of the surgeon to the tip of the instruments offering a comfortable, ergonomically ideal operating position (Stylopoulos & Rattner, 2003). Many studies highlighted that the operating surgeon experienced less physical strain with robotic assisted surgery (Stylopoulos & Rattner, 2003; Ballantyne et al., 2003; Hellan et al., 2007). In addition, robotic technology offers additional features such as motion scaling and remote telesurgical applications including tele-mentoring (Kim & Kang, 2010)

### **4.2 Limitations of the current robotic systems**

The current robotic systems have some limitations which should be addressed in the future. There is lack of both tactile sensation and tensile feedback to the operating surgeon. Therefore, tissue damage can occur easily during traction by the robotic arm and during movement of the robotic instrument (Baik, 2008). Therefore, the surgeon must rely on visual cues to estimate the amount of tension exerted on the tissues (Hellan et al., 2007). Also, suture material can be cut during suturing because there is no tensile feedback to the robotic instrument (Baik, 2008). Therefore, great care must be taken to avoid traumatic injuries when handling bowel.

The system requires precise positioning of the robot for optimal operative outcome and to avoid robotic arm collision and the position of the patient cannot be changed without undocking the robotic arms (Hellan et al., 2007). The docking and separation procedure of a robotic cart from the patient is a time consuming procedure. Also, when using the robot to perform a surgical procedure in different compartments in the abdominal cavity, such as anterior resection, repeated docking and undocking of the robot is often needed and this is reflected on increased operating time. When immediate open conversion is necessary to deal with serious intra-operative bleeding delayed separation of the robotic cart can create a difficult situation (Baik, 2008).

High capital and running costs of the currently available robotic system made the taking up of this technology rather limited in many countries. The average price of one robotic system is more than U\$2,000,000 and combining this with U\$2,000 for the disposable instruments is a major issue when cost-effectiveness of robotic surgery is debated (Baik, 2008).

### **4.3 Approaches to robotic rectal surgery**

There are several techniques for robotic rectal cancer surgery described in the surgical literature.

### **4.3.1 Multiple stages totally robotic technique**

This is described as either a two-stage technique or a three-stage technique (D'Annibale et al., 2004). The number of stages mirrors the number of movements of the robotic cart. The need for frequent docking & undocking of the robotic system is reflected on increased operating time.

### **4.3.2 Hybrid technique**

To eliminate the need for repositioning of the robot most surgeons choose conventional laparoscopic mobilization of the left colon and splenic flexure as well as division of the inferior mesenteric vessels and then use the robot for the TME part of the operation only. This hybrid approach saves the time for repetitive robotic setups. The actual TME is reported to take an average of 60 minutes (Hellan et al., 2007; Baik et al., 2008).

### **4.3.3 Single stage totally robotic**

This approach has been recently reported by Kawak & Kim (2011). It eliminates the need for frequent docking & undocking of the robot but at the same time preserves the advantages of the use of the robotic approach for the whole procedure.

### **4.4 Advantages of totally robotic rectal surgery**

Advocates of the totally robotic approach, whether multiple stage or single stage, believe that robotic dissection around the IMA pedicle is a fundamental step of the procedure to identify and preserve the periaortic nerves. They correctly consider that not only the pelvic nerves but also the periaortic nerves are important in sexual/bladder functions. They also feel that the use of robotics could also improve access and enable easier mobilization of the splenic flexure (Kawak & Kim, 2011).

### **4.5 Learning curve in robotic rectal surgery**

The three-dimensional view and the ability of the robot to transfer the surgeon's hand movements to the tips of the surgical instruments makes the learning curve for robotic surgery much less steep than that for laparoscopic colorectal surgery. Therefore, an inexperienced laparoscopic surgeon is able to operate with the robot safely (Hellan et al, 2007). This is particularly evident for distal rectal cancers as the robot offers superior visualization and mobility during the pelvic dissection (Abodeely et al., 2010). Robotic surgery actually requires the same skill set used during open surgery and thus the learning curve at the console is relatively short (Giulianotti et al., 2003).

The learning curve of robotic assisted technology entails the surgeon's mastery of several unique skills to overcome the loss of tensile and tactile feedback by recognizing visual cues, conceptualize the spatial relationships of robotic instruments outside the active field of view and mentally visualizing the spatial relationships of the robotic arms and cart while operating at the console (Bokhari et al., 2011).

Bokhari et al. (2011) believe that to facilitate the acquisition of robotic unique skills in a safe and stepwise manner, the surgeon should acquire expert laparoscopic skills before using the robotic approach. They divided the learning curve into three phases. Phase 1 to include 15 cases and it represents the initial part of the learning curve. Phase 2 includes an additional 10 cases to allow the consolidation of the additional experience once the initial learning curve has been completed. Phase 3 is the post-learning period when the surgeon can start offering robotic surgery for a more complex and challenging cases. The authors concluded that their data suggest that after a learning curve phase that involves of 15 to 25 cases, the surgeon may achieve a higher level of competence and consider using robotic surgery for patients presenting with more difficult cases safely.

### **4.6 Outcomes of robotic assisted rectal surgery**

64 Contemporary Issues in Colorectal Surgical Practice

There are several techniques for robotic rectal cancer surgery described in the surgical

This is described as either a two-stage technique or a three-stage technique (D'Annibale et al., 2004). The number of stages mirrors the number of movements of the robotic cart. The need for frequent docking & undocking of the robotic system is reflected on increased

To eliminate the need for repositioning of the robot most surgeons choose conventional laparoscopic mobilization of the left colon and splenic flexure as well as division of the inferior mesenteric vessels and then use the robot for the TME part of the operation only. This hybrid approach saves the time for repetitive robotic setups. The actual TME is

This approach has been recently reported by Kawak & Kim (2011). It eliminates the need for frequent docking & undocking of the robot but at the same time preserves the advantages of

Advocates of the totally robotic approach, whether multiple stage or single stage, believe that robotic dissection around the IMA pedicle is a fundamental step of the procedure to identify and preserve the periaortic nerves. They correctly consider that not only the pelvic nerves but also the periaortic nerves are important in sexual/bladder functions. They also feel that the use of robotics could also improve access and enable easier mobilization of the

The three-dimensional view and the ability of the robot to transfer the surgeon's hand movements to the tips of the surgical instruments makes the learning curve for robotic surgery much less steep than that for laparoscopic colorectal surgery. Therefore, an inexperienced laparoscopic surgeon is able to operate with the robot safely (Hellan et al, 2007). This is particularly evident for distal rectal cancers as the robot offers superior visualization and mobility during the pelvic dissection (Abodeely et al., 2010). Robotic surgery actually requires the same skill set used during open surgery and thus the learning

The learning curve of robotic assisted technology entails the surgeon's mastery of several unique skills to overcome the loss of tensile and tactile feedback by recognizing visual cues, conceptualize the spatial relationships of robotic instruments outside the active field of view

reported to take an average of 60 minutes (Hellan et al., 2007; Baik et al., 2008).

**4.3 Approaches to robotic rectal surgery** 

**4.3.1 Multiple stages totally robotic technique** 

literature.

operating time.

**4.3.2 Hybrid technique** 

**4.3.3 Single stage totally robotic** 

splenic flexure (Kawak & Kim, 2011).

**4.5 Learning curve in robotic rectal surgery** 

curve at the console is relatively short (Giulianotti et al., 2003).

the use of the robotic approach for the whole procedure.

**4.4 Advantages of totally robotic rectal surgery** 

### **4.6.1 Evidence from case series reports & case-matched studies**

Pigazzi et al. (2006) reported the first series of robotic-assisted low anterior resection with total mesorectal excision on six consecutive patients with rectal cancer. These cases were compared with six consecutive low anterior resections performed with conventional laparoscopic technique by the same surgeon. There were no conversions in either group. Operative and pathological data, complications, and hospital stay were similar in both groups. However, robotic operations appeared to cause less strain for the operating surgeon. The authors concluded that robotic-assisted laparoscopic low anterior resection for rectal cancer is feasible in experienced hands and the technique may facilitate minimally invasive radical rectal surgery. The same group published 2 further case-matched reports with bigger series (Hellan et al., 2007; Baek et al., 2011) confirming their conclusion from the initial study. They particularly highlighted the low conversion rate with robotic assisted rectal surgery.

Patriti et al. (2009) reported on the short and medium term outcome of robotic assisted and traditional laparoscopic rectal resection in a case matched study. They found that robotassisted laparoscopic rectal resection results in shorter operative time when a total mesorectal excision is performed and significantly lowers conversion rate. Postoperative morbidity was comparable between both groups. Overall survival and disease-free survival were comparable between groups, even though a trend towards better disease-free survival in the robotic assisted group was observed.

Baik et al. (2009) compared the short-term results between robotic-assisted low anterior resection and standard laparoscopic low anterior resection in rectal cancer. Conversion rate and serious complication rate were significantly lower in the robotic surgery group. The specimen quality was acceptable in both groups with a significantly better quality of the mesorectum grading in the robotic group.

Biffi et al. (2011) investigated the estimated blood loss after full robotic low anterior resection in a case-matched model with conventional open approach. Estimated intraoperative blood loss was significantly higher in the open group. They also found that the robotic surgery group had significantly decreased length of hospital stay, increased number of harvested lymph nodes and extent of distal margin.

Pigazzi et al. (2010) reported a multicentre study on the role of robot-assisted tumourspecific rectal surgery (RTSRS) to verify, on a multicentre basis, the peri-operative and oncologic outcome of RTSRS. The study included 140 consecutive patients undergoing RTSR in three centres. Conversion rate was 4. 9%. The number of harvested nodes and margin status compared favourably with those of open series. The 3-year overall survival rate was 97% with no isolated local recurrences were found at mean follow-up of 17. 4 months. The authors concluded that RTSRS is a safe and feasible procedure and highlighted the need for randomized clinical trials and longer follow-up are needed to evaluate a possible influence of RTSRS on patient survival.

Park et al. (2011) compared the short-term outcomes in 263 patients (open group = 88 patients, laparoscopic group n = 123 & robot-assisted group n = 52). Patients from the laparoscopic & robotic assisted groups recovered significantly faster than did those from the open surgery group. The specimen quality, with a distal resection margin, harvested lymph nodes, and circumferential margin, did not differ among the three groups. The authors concluded that laparoscopic & robotic assisted surgery reproduce equivalent short-term results of standard open surgery while providing the advantages of minimal access. For experienced laparoscopic colorectal surgeon, the use of the da Vinci robot resulted in no significant short-term clinical benefit over the conventional laparoscopic approach.

### **4.6.2 Evidence from randomised controlled trials (RCT)**

There is lack of evidence from RCT to support robotic assisted surgery for rectal cancer. The **RO**botic versus **LA**paroscopic **R**esection for **R**ectal cancer **(ROLARR)** is designed to address this issue. This is an international, multicentre, prospective, randomised, controlled, unblinded, parallel-group trial of robotic-assisted versus laparoscopic surgery for the curative treatment of rectal cancer.

The study will perform a rigorous evaluation of robotic-assisted rectal cancer surgery against conventional laparoscopic rectal cancer resection by means of a randomised, controlled trial. Key short-term outcomes will include assessment of technical ease of the operation and improved oncological outcome. Also, quality of life assessment and analysis of cost-effectiveness will be performed. Short-term outcomes will be analysed to provide a timely assessment of the new technology. Longer-term outcomes will focus on oncological aspects of the disease with analysis of disease-free and overall survival and local recurrence rates at 3-year follow-up (http://www. leeds. ac. uk/hsphr/research/AUHE/rolarr. html).

### **5. Extended resection techniques in laparoscopic rectal cancer surgery**

In an attempt to decrease the risk of local recurrence following radical surgery for rectal cancer, techniques have been described which offer extended resection. These were originally described in open surgery, but more recently these extended resections have been also offered laparoscopically (Georgiou et al., 2009; Stelzner et al., 2011).

### **5.1 Laparoscopic extended lateral pelvic node dissection**

Lateral pelvic lymph node involvement in rectal cancer has been well recognised for many years (Sauer et al., 1951). In Japan, lateral pelvic node dissection is performed to minimise

Pigazzi et al. (2010) reported a multicentre study on the role of robot-assisted tumourspecific rectal surgery (RTSRS) to verify, on a multicentre basis, the peri-operative and oncologic outcome of RTSRS. The study included 140 consecutive patients undergoing RTSR in three centres. Conversion rate was 4. 9%. The number of harvested nodes and margin status compared favourably with those of open series. The 3-year overall survival rate was 97% with no isolated local recurrences were found at mean follow-up of 17. 4 months. The authors concluded that RTSRS is a safe and feasible procedure and highlighted the need for randomized clinical trials and longer follow-up are needed to evaluate a possible influence

Park et al. (2011) compared the short-term outcomes in 263 patients (open group = 88 patients, laparoscopic group n = 123 & robot-assisted group n = 52). Patients from the laparoscopic & robotic assisted groups recovered significantly faster than did those from the open surgery group. The specimen quality, with a distal resection margin, harvested lymph nodes, and circumferential margin, did not differ among the three groups. The authors concluded that laparoscopic & robotic assisted surgery reproduce equivalent short-term results of standard open surgery while providing the advantages of minimal access. For experienced laparoscopic colorectal surgeon, the use of the da Vinci robot resulted in no

There is lack of evidence from RCT to support robotic assisted surgery for rectal cancer. The **RO**botic versus **LA**paroscopic **R**esection for **R**ectal cancer **(ROLARR)** is designed to address this issue. This is an international, multicentre, prospective, randomised, controlled, unblinded, parallel-group trial of robotic-assisted versus laparoscopic surgery for the

The study will perform a rigorous evaluation of robotic-assisted rectal cancer surgery against conventional laparoscopic rectal cancer resection by means of a randomised, controlled trial. Key short-term outcomes will include assessment of technical ease of the operation and improved oncological outcome. Also, quality of life assessment and analysis of cost-effectiveness will be performed. Short-term outcomes will be analysed to provide a timely assessment of the new technology. Longer-term outcomes will focus on oncological aspects of the disease with analysis of disease-free and overall survival and local recurrence rates at 3-year follow-up (http://www. leeds. ac. uk/hsphr/research/AUHE/rolarr. html).

**5. Extended resection techniques in laparoscopic rectal cancer surgery** 

also offered laparoscopically (Georgiou et al., 2009; Stelzner et al., 2011).

**5.1 Laparoscopic extended lateral pelvic node dissection** 

In an attempt to decrease the risk of local recurrence following radical surgery for rectal cancer, techniques have been described which offer extended resection. These were originally described in open surgery, but more recently these extended resections have been

Lateral pelvic lymph node involvement in rectal cancer has been well recognised for many years (Sauer et al., 1951). In Japan, lateral pelvic node dissection is performed to minimise

significant short-term clinical benefit over the conventional laparoscopic approach.

**4.6.2 Evidence from randomised controlled trials (RCT)** 

of RTSRS on patient survival.

curative treatment of rectal cancer.

local recurrence and improve survival as they believe that total mesorectal excision does not clear the metastases in the lateral pelvic lymph nodes which has an overall incidence between 8. 6 to 27% (Fujita et al., 2003; Kim et al., 2008). However, evidence from metaanalysis confirms that extended lateral pelvic node dissection is associated with increased blood loss and urinary and sexual dysfunction without significant overall cancer-specific advantage (Georgiou et al., 2009). Therefore, preoperative radiotherapy or chemoradiotherapy followed by rectal resection with total mesorectal excision is the standard treatment in Western countries.

There is limited evidence in the literature on the outcomes of laparoscopic extended lateral pelvic node dissection with total meseorectal excision in patients with locally advanced rectal cancer. Advocates of the technique believe that laparoscopic approach has the potential to decrease the well known drawbacks of the open lateral pelvic wall dissection as the magnified views offer clear vision of the smallest structures in the narrow pelvis which make it easier to identify lymphatic tissue and protect the autonomic nerve plexus (Park et al., 2011). Some studies also suggest decreased blood loss and operative time with the laparoscopic approach (Fujita et al., 2003). Increasingly, robotic assisted approach has been used to perform extended lateral pelvic wall lymphadenectomy with remarks that dissection of the lymph nodes around major pelvic vessels is much easier (Park et al., 2011).

However, the currently available evidence is rather limited to make valid conclusions on the safety and outcomes of laparoscopic or robotic-assisted extended lateral pelvic node dissection in locally advanced rectal cancer.

### **5.2 Laparoscopic extended abdominoperineal resection for low rectal cancer**

Standard abdominoperineal resection (APR) is well known to be associated with inferior oncological outcomes when compared to anterior resection for low rectal cancer (Stelzner et al., 2011). This is attributed to the relatively high incidence of intra-operative tumour or bowel perforation and positive circumferential resection margin due to the relative lack of the mesorectal fat around the lower rectum (Nagtegaal et al, 2005). This led to progressive development of an extended version of APR, now known as extended abdominoperineal resection (EAP), extralevator abdominoperineal excision (ELAP) or cylindrical abdominoperineal resection (Holm et al, 2007; Marecik et al, 2011). This technique aims at a wider circumferential resection margin at the level of the tumour bearing segment. Systematic reviews suggests that extended techniques of APR result in superior oncologic outcome in terms of lower incidence of tumour perforation and positive circumferential resection margin when compared to standard techniques (Stelzner et al., 2011).

However, extended abdominoperineal resection has been reported to be associated with higher incidence of perineal wound complications and hernia in comparison with the conventional APR. Also, lateral relatively blind excision of the levator muscles can put the neurovascular structures along the lateral pelvic wall at risk for injury which could increase the morbidity of the procedure. There are limited reports in the literature on laparoscopic and robotic assisted extended abdominoperineal resection (Marecik et al, 2011). However, the data so far are limited and more research is needed to assess the specific value of laparoscopic and robotic-assisted approach in relation to extended abdominoperineal resection.

### **6. Other approaches for laparoscopic rectal cancer surgery**

There are few reports in the literature describing alternative approaches to rectal cancer surgey including single port access mesorectal excision (Gaujoux et al., 2011; Bulut et al., 2011; Lauritsen & Bulut, 2011), transanal or transvaginal retrieval of the specimen (Choi et al., 2009). However, the number of studies & cases are limited to make any valid conclusions. There is slow, but steadily increasing, interest in the application of completely natural orifice transluminal surgery (NOTES) in colorectal surgery (Sylla, 2010).

### **7. Conclusion**

The debate over the optimal approach to the laparoscopic resection of rectal cancer is far from over. The short-term outcomes of conventional laparoscopic resections by experienced laparoscopic surgeons are better than those of open surgery and seem to be improving over time. The role of robotic assisted rectal surgery still needs to be better defined. There is limited evidence whether laparoscopic approach confers any long-term benefits for the patients. Also, further research is needed to establish if the different laparoscopic approaches can vary in their effect on the long term prognosis.

### **8. References**


There are few reports in the literature describing alternative approaches to rectal cancer surgey including single port access mesorectal excision (Gaujoux et al., 2011; Bulut et al., 2011; Lauritsen & Bulut, 2011), transanal or transvaginal retrieval of the specimen (Choi et al., 2009). However, the number of studies & cases are limited to make any valid conclusions. There is slow, but steadily increasing, interest in the application of completely

The debate over the optimal approach to the laparoscopic resection of rectal cancer is far from over. The short-term outcomes of conventional laparoscopic resections by experienced laparoscopic surgeons are better than those of open surgery and seem to be improving over time. The role of robotic assisted rectal surgery still needs to be better defined. There is limited evidence whether laparoscopic approach confers any long-term benefits for the patients. Also, further research is needed to establish if the different laparoscopic

Abodeely, A.; Lagares-Garcia, J. A.; Duron, V.; Vrees M. (2010). Safety and learning curve in

Anderson, C.; Uman, G.; Pigazzi, A. (2008). Oncologic outcomes of laparoscopic surgery for

Aziz, O.; Constantinides, V.; Tekkis, P.; et al. (2006). Laparoscopic versus open-surgery for

Baek, J. H.; Pastor, C.; Pigazzi, A. (2011). Robotic and laparoscopic total mesorectal excision

Baik, S. H.; Lee, W. J.; Rha, K. H.; Kim, N. K.; Sohn, S. K.; Chi, H. S.; Cho, C. H.; Lee, S. K.;

Baik, S. H.; Kwon, H. Y.; Kim, J. S.; Hur, H; Sohn, S. K.; Cho, C. H.; Kim, H . (2009). Robotic

Ballantyne, G. H.; Merola, P.; Weber, A.; Wasielewski, A. (2001). Robotic solutions to the

Ballantyne, G. H. (2002). Robotic surgery, telerobotic surgery, telepresence, and telementoring: review of early clinical results. Surg Endosc 16:1389–1402 Ballantyne, G. H.; Moll, F. (2003). The da Vinci telerobotic surgical system: the virtual operative field and telepresence surgery. Surg Clin North Am.; 83:1293–1304 Biffi, R.; Luca, F.; Pozzi, S.; Cenciarelli, S.; Valvo, M.; Sonzogni, A.; Radice, D.; Ghezzi, T. L.

rectal cancer: a systematic review and meta-analysis of the literature. Eur J Surg

Cheon, J. H.; Ahn, J. B.; Kim, W. H. (2008). Robotic total mesorectal excision for

versus laparoscopic low anterior resection of rectal cancer: short-term outcome of a

(2011). Operative blood loss and use of blood products after full robotic and conventional low anterior resection with total mesorectal excision for treatment of

**6. Other approaches for laparoscopic rectal cancer surgery** 

approaches can vary in their effect on the long term prognosis.

robotic colorectal surgery. J Robotic Surg; 4:161–165

rectal cancer: a meta-analysis. Ann Surg Onc;13:413–424

Baik, S. H. (2008). Robotic colorectal surgery. Yonsei Med J.; 31; 49(6):891-6

for rectal cancer: a case-matched study. Surg Endosc; 25:521–525

rectal cancer using four robotic arms. Surg Endosc 22:792–797

prospective comparative study. Ann Surg Oncol.; 16(6):1480-7

pitfalls of laparoscopic colectomy. Osp Ital Chir;7:405-12

rectal cancer. J Robot Surg.; 5(2):101-107

**7. Conclusion** 

**8. References** 

Oncol; 34(10)1135–42

natural orifice transluminal surgery (NOTES) in colorectal surgery (Sylla, 2010).


laparoscopicassisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicentre, randomised controlled trial. Lancet; 365: 1718–26


Heald, R. J.; Moran, B. J.; Ryall, R. D.; Sexton, R.; MacFarlane, J. K. (1998). Rectal cancer: the

Hellan, M.; Anderson, C.; Ellenhorn, J. D.; Paz, B.; Pigazzi, A. (2007). Short-term outcomes

Holm, T.; Ljung, A.; Häggmark, T.; Jurell, G.; Lagergren, J. (2007). Extended

Ito, M.; Sugito, M.; Kobayashi, A.; Nishizawa, Y.; Tsunoda, Y.; Saito, N. (2008),. Relationship

Kang, S. B.; Park, J. W.; Jeong, S. Y.; Nam, B. H.; Choi, H. S. et al (2010). Open versus

Kim, T. H.; Jeong, S. Y.; Choi, D. H.; Kim, D. Y.; Jung, K. H.; Moon, S. H.; Chang, H. J.; Lim,

chemoradiotherapy and curative resection. Ann Surg Oncol; 15:729–737 Kim, J. S.; Cho, S. Y.; Min, B. S.; Kim, N. K. (2009). Risk factors for anastomotic leakage after

Kim, N. K. & Kang, J. (2010). Optimal Total Mesorectal Excision for Rectal Cancer: the Role of Robotic Surgery from an Expert's View. J Korean Soc Coloproctol.; 26(6):377-87 Kwak, J. M., Kim, S. G. (2011). The technique of single-stage totally robotic low anterior

Lacy, A. M.; Garcia-Valdecasas, J. C.; Delgado, S.; Castells, A.; Taurá, P.; Piqué, J. M. et al.

Lanfranco, A. R.; Castellanos, A. E.; Desai, J. P.; Meyers, W. C. (2004). Robotic surgery: a

Laurent, C.; Leblanc, F.; Gineste, C.; Saric, J.; Rullier, E. (2007). Laparoscopic approach in

Lauritsen, M. L.; Bulut, O. (2011). Single-port access laparoscopic abdominoperineal

nonmetastatic colon cancer: a randomized trial. Lancet; 359: 2224–9

surgical treatment of rectal cancer. Br J Surg; 94(12):1555–61

leakage after laparoscopic rectal resection. Int J Colorectal Dis; 23:703-7 Jacobs, M.; Verdeja, J. C.; Goldstein, H. S. (1991). Minimally invasive colon resection

(laparoscopic colectomy). Surg Laparosc Endosc 1: 144–50

randomised controlled trial. Lancet Oncol.; 11(7):637-45

trial): multicentre, randomised controlled trial. Lancet; 365: 1718–26 Fujita, S.; Yamamoto, S.; Akasu, T.; Moriya, Y. (2003). Lateral pelvic lymph node dissection

Lancet; 28; 1(8496):1479-82

floor for rectal cancer. Br J Surg; 94:232–238

technique. J Am Coll Surg; 209:694-701

current perspective. Ann Surg.; 239:14–21

resection. J Robotic Surg; 5:25–28

of print]

133(8):894–899

14(11):3168-73

laparoscopicassisted surgery in patients with colorectal cancer (MRC CLASICC

for advanced lower rectal cancer. Br J Surg; 90:1580–1585. Heald, R. J.; Ryall, R. D. (1986). Recurrence and survival after total mesorectal excision for rectal cancer.

Basingstoke experience of total mesorectal excision, 1978-1997. Arch Surg;

after robotic-assisted total mesorectal excision for rectal cancer. Ann Surg Oncol.;

abdominoperineal resection with gluteus maximus flap reconstruction of the pelvic

between multiple numbers of stapler firings during rectal division and anastomotic

laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): short-term outcomes of an open-label

S. B.; Choi, H. S.; Park, J. G. (2008). Lateral lymph node metastasis is a major cause of locoregional recurrence in rectal cancer treated with preoperative

laparoscopic intracorporeal colorectal anastomosis with a double stapling

(2002). Laparoscopy-assisted colectomy versus open colectomy for treatment of

resection through the colostomy site: a case report. Tech Coloproctol. [Epub ahead


**Part 3** 

**Emergency Colorectal Surgery** 

72 Contemporary Issues in Colorectal Surgical Practice

Quah, H. M.; Jayne, D. G.; Eu, K. W.; Seow-Choen, F. (2002). Bladder and sexual dysfunction

Quirke, P.; Dixon, M. F. (1988). The prediction of local recurrence in rectal adenocarcinoma

Sauer, I.; Bacon, H. E. (1951). Influence of lateral spread of cancer of the rectum on

Scheidbach, H.; Schneider, C.; Konradt, J. et al. (2002). Laparoscopic abdominoperineal

Shalli, K.; MacDonald, E.; Aly, E. H. (2009). Towards lower complication rate in laparoscopic

Simons, A. J.; Anthone, G. J.; Ortega, A. E.; et al. (1995). Laparoscopic-assisted colectomy

Stelzner, S.; Koehler, C.; Stelzer, J.; Sims, A.; Witzigmann, H. (2011). Extended

Stylopoulos, N.; Rattner, D. (2003). Robotics and ergonomics. Surg Clin North Am.; 83:1321–

Sylla; P. (2010). Current experience and future directions of completely NOTES colorectal

Tekkis; P. P.; Senagore; A. J.; Delaney, C. P., Fazio, V. W. (2005). Evaluation of the learning

Veldkamp, R.; Kuhry, E.; Hop, W. C.; Jeekel, J.; Kazemier, G.; Bonjer, H. J. et al. (2005). Colon

Vithiananthan, S.; Cooper, Z.; Betten, K.; et al. (2001). Hybrid laparoscopic flexure takedown

by histopathological examination. Int J Colorectal Dis.; 3(2):127-31

radicability of operation and prognosis. Am J Surg; 81:111–120

rectal surgery. Colorectal Disease, 11 (Suppl. 2), 55. Abstract

cancer-a systematic overview. Int J Colorectal Dis.; 26(10):1227-40

learning curve. Dis Colon Rectum; 38: 600–03

resection. World J Gastrointest Surg.; 2(6): 193-198

resections. Ann Surg; 242(1):83–91

randomised trial. Lancet Oncol; 6: 477–84

cancer. Br J Surg; 89:1551–1556

Surg Endosc; 16:7–13

37

following laparoscopically assisted and conventional open mesorectal resection for

resection and anterior resection with curative intent for carcinoma of the rectum.

abdominoperineal excision vs. standard abdominoperineal excision in rectal

curve in laparoscopic colorectal surgery: comparison of right-sided and left-sided

cancer Laparoscopic or Open Resection Study Group (COLOR). Laparoscopic surgery versus open surgery for colon cancer: short-term outcomes of a

and open procedure for rectal resection is associated with significantly shorter length of stay than equivalent open resection. Dis Colon Rectum; 44(7):927–935 Zhu, Q. L.; Feng, B.; Lu, A. G.; Wang, M. L.; Hu, W. G.; Li, J. W.; Mao, Z. H.; Zheng, M. H.

(2010). Laparoscopic low anterior resection for rectal carcinoma: complications and management in 132 consecutive patients. World J Gastroenterol.; 16(36):4605-10

## **Emergency Surgery for Colorectal Cancer Complications: Obstruction, Perforation, Bleeding**

Gelu Osian *University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj-Napoca Romania* 

### **1. Introduction**

Colorectal cancer represents the third most common cause of malignancy in men and the fourth most common cause of malignancy in women. Prevalence is estimated at 25 to 100,000 inhabitants (1).

Left colon cancer is more frequent than right colon cancer with half of colorectal cancers being situated at the level of the sigmoid colon.

There is a higher incidence of this form of malignancy in developed countries with higher living and is thought to be mainly due to environmental factors. An improvement in survival of the patients has been obtained thanks to national screening programs which enables diagnosis in the early stages which allows for treatment.

Despite current screening guidelines a large number of cases present to the surgical clinic as complications of colorectal cancer in the advanced, such as are tumoral obstruction, colon perforation, and lower GI hemorrhage.

The age of patients presenting with these complications is generally advanced, a factor which contributes to a high post-operative mortality of patients. Malignant processes evolve over a longer period in order for these complications to be produced, which is why patients are usually found to be in advanced stages of oncologic evolution with peritoneal carcinomatosis or distance metastasis. Despite this fact, radical treatment for the complicated colorectal cancer is recommended whenever possible.

### **2. Obstruction from colorectal cancer**

The great majority of colorectal cancers have an asymptomatic or paucisymptomatic evolution over an extended period of time until they succeed in being clinically determined by a major complication. This is often a lower intestinal occlusion. Several cases have been cited whereby patients have beencompletely asymptomatic but have a sudden clinical onset. This was reported as a result of air flights, but without establishing a correlation between the flight and onset of disease (2).

Of the total colorectal cancers (CRC) 8-10% present as bowel occlusions, their variability being registered depending on the specificity of the surgical service. They do not tend to have a favorable prognosis due to the increased age of patients, the advanced stage and the emergency nature of the surgical intervention (3).

Cancer represents the most frequent cause of large bowel obstruction, comprising 60% of the occlusions in elderly patients. Two thirds of colorectal cancers are situated at the left colon level and one third at right colon level (4).

Intestinal occlusion due to CRC has always raised problems regarding surgical treatment. Due to the fact that most of these patients are operated as an emergency, their metabolic state is insufficiently assessed and mechanically, the colon is not ready for surgical intervention. Surgical teams must make an ongoing choice between surgical treatments in one operative session and serialized surgical interventions. At present the most common choice is usually made for resection with primary anastomosis (5).

### **2.1 Presentation**

Patients present to surgical clinic with abdominal colic pains, abdominal distension, altered mental status, and cessation of bowel transit of gas and feces. The patient is usually elderly, with altered general state, signs of neoplastic toxicity, and rich hyperseptic colon content.

As opposed to small bowel occlusions, colic-like pains are less frequent and less intense. Intestinal distension comprises solely the colic framework for a long period of time and only later does it extend to the small bowel. At this point, fecal vomiting occurs. The mechanism of vomiting is through a a reflex mechanism present in abdominal colic. On exam, distension of the abdomen on the colic frame shows dullness on percussion. In older occlusions, distension with dullness comprises the whole abdomen.

The abdomen is slightly sensitive spontaneously and to palpation. On auscultation, can be noted accentuated bowel sounds are detected. In older occlusive forms, the absence of sounds due to the presence of paralytic ileus.

At the per rectum examination, an empty rectal ampule is detected, without fecal matter. Quite often in lower rectal cancers, the tumor, which is completely stenotic, may be palpated by the exploratory finger.

Following fecal vomiting and abdominal fluid sequestration, the patient shows signs of dehydration and shock with cold, cyanotic, dried teguments and low blood pressure .

### **2.2 Diagnosis**

Abdominal X-ray emphasizes few hydro-aeric levels situated in the colonic frame, and having a large diameter vertically. This investigation can therefore make a diagnosis of a large bowel obstruction. Abdominal ultrasound shows dilated intestinal loops with liquid content and bracing movements. It can also reveal free liquid in the peritoneal cavity, can highlight the mass formed at the colon level if it is of significant size and can also observe potential metastatic disseminations to other abdominal organs.

Abdominal CT diagnoses the obstruction and can detect the primary tumor with its potential secondary determinations with a greater precision than abdominal ultrasound.

When the general state of the patients enables, a colonoscopy can be performed, highlighting the colorectal cancer, taking a biopsy and also perform potential trans-tumoral drilling which can relieve the obstruction with the possibility of a delayed emergency surgical intervention.

A chest X Ray can also detect potential secondary pulmonary metastasis.

Due to the older age of patients and their multiple co-morbidities, an extensive preoperative assessment is necessary, measuring creatinine, urea and electrolytes and arterial blood gases. Patients are usually dehydrated suffering from severe metabolic imbalances which must be treated at the preoperative stage.

The ECG is Compulsory part of the surgical preoperative protocol.

### **2.3 Differential diagnosis**

76 Contemporary Issues in Colorectal Surgical Practice

have a favorable prognosis due to the increased age of patients, the advanced stage and the

Cancer represents the most frequent cause of large bowel obstruction, comprising 60% of the occlusions in elderly patients. Two thirds of colorectal cancers are situated at the left colon

Intestinal occlusion due to CRC has always raised problems regarding surgical treatment. Due to the fact that most of these patients are operated as an emergency, their metabolic state is insufficiently assessed and mechanically, the colon is not ready for surgical intervention. Surgical teams must make an ongoing choice between surgical treatments in one operative session and serialized surgical interventions. At present the most common

Patients present to surgical clinic with abdominal colic pains, abdominal distension, altered mental status, and cessation of bowel transit of gas and feces. The patient is usually elderly, with altered general state, signs of neoplastic toxicity, and rich hyperseptic colon content. As opposed to small bowel occlusions, colic-like pains are less frequent and less intense. Intestinal distension comprises solely the colic framework for a long period of time and only later does it extend to the small bowel. At this point, fecal vomiting occurs. The mechanism of vomiting is through a a reflex mechanism present in abdominal colic. On exam, distension of the abdomen on the colic frame shows dullness on percussion. In older

The abdomen is slightly sensitive spontaneously and to palpation. On auscultation, can be noted accentuated bowel sounds are detected. In older occlusive forms, the absence of

At the per rectum examination, an empty rectal ampule is detected, without fecal matter. Quite often in lower rectal cancers, the tumor, which is completely stenotic, may be palpated

Following fecal vomiting and abdominal fluid sequestration, the patient shows signs of dehydration and shock with cold, cyanotic, dried teguments and low blood pressure .

Abdominal X-ray emphasizes few hydro-aeric levels situated in the colonic frame, and having a large diameter vertically. This investigation can therefore make a diagnosis of a large bowel obstruction. Abdominal ultrasound shows dilated intestinal loops with liquid content and bracing movements. It can also reveal free liquid in the peritoneal cavity, can highlight the mass formed at the colon level if it is of significant size and can also observe

Abdominal CT diagnoses the obstruction and can detect the primary tumor with its potential secondary determinations with a greater precision than abdominal ultrasound.

When the general state of the patients enables, a colonoscopy can be performed, highlighting the colorectal cancer, taking a biopsy and also perform potential trans-tumoral drilling which can relieve the obstruction with the possibility of a delayed emergency surgical intervention.

emergency nature of the surgical intervention (3).

choice is usually made for resection with primary anastomosis (5).

occlusions, distension with dullness comprises the whole abdomen.

potential metastatic disseminations to other abdominal organs.

sounds due to the presence of paralytic ileus.

by the exploratory finger.

**2.2 Diagnosis** 

level and one third at right colon level (4).

**2.1 Presentation** 

A diagnosis of large bowel obstruction can be made with the aid of history taking, the objective examination, and also the additional investigations performed. However, a differential diagnosis is required mainly having to rule out small bowel obstructions with higher intestinal occlusions. These usually determine a more painful and prominent symptomatology, with more frequent and intense colicky pains, with frequent food vomiting and only later, in neglected obstructions, they become fecaloid. Abdominal X Ray highlights hydroaeric levels with central disposition, having a large diameter on the horizontal plane. Other causes must also be ruled out including intussusception, sigmoid volvulus, engagement of the colon in a hernia sac with strangulation, invasion of the colon in the framework of extension of a neoplastic process from proximity (stomach, genital, urinary, pancreas etc).

Once the tumoral cause of the obstruction is established, a differential diagnosis of causes of colonic tumors is necessary, namely stenosed vegetating benign tumors, phytobezoar etc. Often the decision for surgical treatment is made in an emergency and the final diagnosis is only made intra-operative.

### **2.4 Preoperative treatment**

Preoperative assessment and treatment must be carefully and rapidly undertaken, in order to avoid delay of a surgical intervention in patients who may have altered mental status or unstable vital signs. Metabolic acidosis, hypo or hyperglycemia and electrolyte imbalances are corrected based on the previous investigations performed. Antibiotics are administered prophylactically at this stage and the choice is usually a second or third generation cephalosporin in conjuction with Metronizadole or Vancomycin. Also, prophylaxis of deep venous thrombosis prophylaxis is achieved with low molecular weight heparin. Symptomatic treatment may be given to relieve the distress and may includes, analgesics, antiemetics, gastric antisecretion drugs and anticholinergics (6).

Oral laxatives are contra indicated.

If there is a probability that the surgical intervention includes a colostomy, it is advisable to mark the pre-operated place of colostomy.

All other co-morbidities must be optimized whenever possible.

### **2.5 Treatment options**

In the therapeutic strategy of obstructive colorectal cancer, application of palliative methods and other radical treatment methods are advised.. Whenever possible, treatment has to be radical.

Palliative treatment is recommended in patients with severely altered general health and advanced stage disease with hepatic non- resectable metastasis (7).

Palliative treatment can be carried out as follows: pneumatic dilation of the tumorally stenosed region with the help of a balloon or rechanneling with laser Nd-YAG which can be effective as a palliative method in 80-90% of patients.

Endoscopic setting of the auto expandable metallic prosthesis has been used more and more with greater success in the preparation of the radical or palliative surgery for a nonresectable obstructive cancer. If this procedure is performed by an experienced surgeon, the success rate is over 90% (8).

In the operable cases, the implanted stent allows the gastrointestinal transit to restart while resolving the obstruction at the same time. Subsequently, the patient's condition and biological parameters improve, also permitting the delivery of neoadjuvant therapy where needed (9).

The affected bowel reduces its dimensions, the edema disappears and blood perfusion to the bowel improves. All of these changes create the premise for a planned radical intervention to be performed. A study done by Tekkis (8) looked at two groups of patients with obstructive colon cancer and similar tumor stages. One group had an initial surgical treatment and the other group had the endoscopic prosthesis as a first step followed by a surgical intervention. In the group who received the stent prosthesis, there were 87% of cases who ended up having resection and anastomosis, compared to 41% of cases in the non-stented group.

The specific complications associated with stoma care have to be considered, as they potentially increase co-morbidities, hospital admission, and also the costs of the intervention. The post-operative evolution was better in the group of patients who received the endoscopic stent, and they also had a shorted hospital admission (8). Performing elective surgical interventions also proved to decrease post-operatory mortality.

Inserting expandable metallic stents is the intervention of choice for tumors in the advanced stages, with metastasis and peritoneal carcinomatosis.

A study done by Jeffrey H. Lee et al (10) showed that this method is safe and feasible. When it was performed by an experienced team, it had a success rate of 94%. Re-obstruction caused by the tumoral proliferation was noted in 7.3% cases. Death occurred due to specific complications related to the neoplastic process rather than surgical interventions.

Some of the disadvantages of the stenting process are related to the iatrogenic complications as a result of inserting the prosthesis in emergency conditions. Watt et al (11) noted that the rate of complications was of 27%. These include stent migration (11%), perforation (4.5%) and tumoral growth with stent obstruction (12%).

Radical treatment can be performed during a surgical intervention or during serialized interventions. In the course of history, the following were performed: at the end of the 19th century Paul-Mikulicz performed the intervention in one single operative session through externalizing the colon together with the tumor, which was resected postoperatively and an external anastomosis with a special clamp was performed. This operation was performed in one single intervention and has the advantage of lowering operative mortality by 70% compared to previous procedures, but also has the disadvantage of a high local recurrence. At the beginning of the 20th century the procedure used was one completed in three separate interventions:


Palliative treatment is recommended in patients with severely altered general health and

Palliative treatment can be carried out as follows: pneumatic dilation of the tumorally stenosed region with the help of a balloon or rechanneling with laser Nd-YAG which can be

Endoscopic setting of the auto expandable metallic prosthesis has been used more and more with greater success in the preparation of the radical or palliative surgery for a nonresectable obstructive cancer. If this procedure is performed by an experienced surgeon, the

In the operable cases, the implanted stent allows the gastrointestinal transit to restart while resolving the obstruction at the same time. Subsequently, the patient's condition and biological parameters improve, also permitting the delivery of neoadjuvant therapy where needed (9). The affected bowel reduces its dimensions, the edema disappears and blood perfusion to the bowel improves. All of these changes create the premise for a planned radical intervention to be performed. A study done by Tekkis (8) looked at two groups of patients with obstructive colon cancer and similar tumor stages. One group had an initial surgical treatment and the other group had the endoscopic prosthesis as a first step followed by a surgical intervention. In the group who received the stent prosthesis, there were 87% of cases who ended up having

The specific complications associated with stoma care have to be considered, as they potentially increase co-morbidities, hospital admission, and also the costs of the intervention. The post-operative evolution was better in the group of patients who received the endoscopic stent, and they also had a shorted hospital admission (8). Performing elective

Inserting expandable metallic stents is the intervention of choice for tumors in the advanced

A study done by Jeffrey H. Lee et al (10) showed that this method is safe and feasible. When it was performed by an experienced team, it had a success rate of 94%. Re-obstruction caused by the tumoral proliferation was noted in 7.3% cases. Death occurred due to specific

Some of the disadvantages of the stenting process are related to the iatrogenic complications as a result of inserting the prosthesis in emergency conditions. Watt et al (11) noted that the rate of complications was of 27%. These include stent migration (11%), perforation (4.5%)

Radical treatment can be performed during a surgical intervention or during serialized interventions. In the course of history, the following were performed: at the end of the 19th century Paul-Mikulicz performed the intervention in one single operative session through externalizing the colon together with the tumor, which was resected postoperatively and an external anastomosis with a special clamp was performed. This operation was performed in one single intervention and has the advantage of lowering operative mortality by 70% compared to previous procedures, but also has the disadvantage of a high local recurrence. At the beginning of the 20th century the procedure used was one completed in three separate

complications related to the neoplastic process rather than surgical interventions.

resection and anastomosis, compared to 41% of cases in the non-stented group.

surgical interventions also proved to decrease post-operatory mortality.

stages, with metastasis and peritoneal carcinomatosis.

and tumoral growth with stent obstruction (12%).

interventions:

advanced stage disease with hepatic non- resectable metastasis (7).

effective as a palliative method in 80-90% of patients.

success rate is over 90% (8).

3. restoring the intestinal transit. The advantage of this method is that it was performed on a mechanically stable colon but had the great disadvantage of a high morbidity rate of 30% (30% the morbidity rate) and mortality of 7% for each operative intervention In 1921, Hartmann proposed a procedure divided into two phases resection of the tumor with terminal colostomy subsequently followed by restoring of the intestinal transit. The advantage consists of rapid removal of the tumor and resolving the occlusion. The anastomosis is not performed on unfavorable terms, but the disadvantage is that of summation of mortality and morbidity indexes for each operative session, given that reintegration in transit is made through a new laparotomy.

The objective of analyzing the historical data was to avoid serialized operative disadvantages and surgical intervention in one operative session with primary anastomosis as the preferred option (12), (13).

### **2.6 Surgical options in obstructive colorectal cancers**

Surgical attitude is different depending on the localization of tumor.

In right colon cancers the indicated operation is right hemicolectomy with primary ileotransverse anastomosis. In elderly patients with increasing age, a significantly altered general state or peritoneal carcinomatosis, the accepted operation is ileotransverse anastomosis with short circuiting of the tumoral obstacle.

In transverse colon cancers, the unanimously accepted surgical intervention is the single resection with a primary anastomosis. In special cases with very significant colon distension, elderly patients with multiple organic deficiencies, a very altered general state or peritoneal carcinomatosis, two phases are indicated for the intervention: colostomy immediately upwards from the tumor then followed by segmentary resection with colo-colonic anastomosis.

Cancers localized to the left colon level have the greatest number of controversies regarding operations in a single session or in two sessions. It is ideal to have a left hemicolectomy with primary colo-rectal anastomosis. If there is an insufficient preparation of the colon, there is a leakage at the hydro-pneumatic test, or anastomosis tension, a protection colostomy is recommended for execution or a provisional ileostomy. If there is severe distension of the colon, technical difficulties in resecting the tumor or ASA (American Society of Anesthesiologists) score >3 (high operative risk), a two step surgical intervention is recommended. The primary step consists of a colostomy, which frees the patient from occlusion, or Hartmann type operation, and resection with anastomosis, or anstomosis as secondary step, respectively. Due to the fact that many patients with left colon cancer are admitted for surgical intervention with an obstruction which evolves over a longer period and therefore there is marked distension of the entire colonic frame, in such cases subtotal colectomy with primary anastomosis was proposed. The advantages of the procedure consisted of removing potential synchronous cancers which were left undiagnosed at the preoperative stage due to the urgent nature of the surgical intervention. Also there is a small risk of fistula for the ileo-colonic anastomosis, similar to that of elective surgery,. The procedure eliminates the necessity for post operative follow-up colonoscopy. Disadvantages consist of extending the surgical intervention with a subsequent increase in operative risk and in the presence of numerous stools postoperatively. There are still a multitude of controversies regarding the treatment of such lesions.

In rectal cancers surgical attitude is dictated by the patient's general state, localization and oncologic stage of the tumor. Either an anterior rectum resection of the tumor with primary anastomosis, a Hartmann operation or a simple colostomy can be performed.

### **2.7 Postoperative treatment**

At the post operative stage, intensive rebalancing of the patient is continued, low molecular weight heparin is administered prophylactically to prevent thromboembolic complications and a further prophylactic dose of antibiotic is administered.

Drainage disturbances are monitored and suppressed as early as possible. Nutrition with liquid intake is restarted upon resolution of the ileus, followed by solid food once intestinal transit is restored.

Skin threads are suppressed 7 to 10 days post operatively.

The results of surgical treatment are less effective because they are performed in emergency situations and add multiple surgical risk factors. In 2005, Coco detected a 44% morbidity and a 4% mortality in emergency surgery of these tumors compared to 12% morbidity and 0% mortality in the elective surgery of the of tumors in the same locations (14).

Zhang MS and his collaborators (15) highlighted the fact that the prognosis of patients with occlusive neoplasms of the left colon and of the rectum depends on the TNM stage of the disease, the preoperative level of CEA, and the radical nature of the surgical intervention.

Localization of the occlusive tumor does not influence the prognosis (16).

### **2.8 Personal experience**

In the Surgery Clinic No III from Cluj-Napoca, the treatment approach of occlusive colorectal cancers is surgical. In all situations where the disease is potentially treatable and the general and local state of the patient enables, resection is performed within oncologic safety limits as well as regional lymphadenectomy with reconstruction of continuity through primary anastomosis. If the bowel is highly distended and edematous, a Hartmann type intervention is performed or a resection with anastomosis and protective ileostomosis. In patients with severely altered general state, in those with a surgically surpassed disease, an upward colostomy or internal derivation is performed.

### **2.9 Conclusion**

Occlusive colorectal cancers are severe forms of disease which represent a serious problem of therapeutic strategy, that is still intensely debated at present. Whenever possible, a radical surgical treatment is indicated with a single operative resection and primary anastomosis.

### **3. Perforated CRC**

The incidence of perforated colorectal cancer is approximately 2.3-2.5% of the total number of surgically treated colorectal cancers (3). This is not a very common complication; however it is very serious due to the severe peritonitis that results. Perforations of the colon have been documented in the literature after administration of bevacizumab for malignant tumors of the colon (17).

### **3.1 Introduction**

80 Contemporary Issues in Colorectal Surgical Practice

and in the presence of numerous stools postoperatively. There are still a multitude of

In rectal cancers surgical attitude is dictated by the patient's general state, localization and oncologic stage of the tumor. Either an anterior rectum resection of the tumor with primary

At the post operative stage, intensive rebalancing of the patient is continued, low molecular weight heparin is administered prophylactically to prevent thromboembolic complications

Drainage disturbances are monitored and suppressed as early as possible. Nutrition with liquid intake is restarted upon resolution of the ileus, followed by solid food once intestinal

The results of surgical treatment are less effective because they are performed in emergency situations and add multiple surgical risk factors. In 2005, Coco detected a 44% morbidity and a 4% mortality in emergency surgery of these tumors compared to 12% morbidity and

Zhang MS and his collaborators (15) highlighted the fact that the prognosis of patients with occlusive neoplasms of the left colon and of the rectum depends on the TNM stage of the disease, the preoperative level of CEA, and the radical nature of the surgical intervention.

In the Surgery Clinic No III from Cluj-Napoca, the treatment approach of occlusive colorectal cancers is surgical. In all situations where the disease is potentially treatable and the general and local state of the patient enables, resection is performed within oncologic safety limits as well as regional lymphadenectomy with reconstruction of continuity through primary anastomosis. If the bowel is highly distended and edematous, a Hartmann type intervention is performed or a resection with anastomosis and protective ileostomosis. In patients with severely altered general state, in those with a surgically surpassed disease,

Occlusive colorectal cancers are severe forms of disease which represent a serious problem of therapeutic strategy, that is still intensely debated at present. Whenever possible, a radical surgical treatment is indicated with a single operative resection and

The incidence of perforated colorectal cancer is approximately 2.3-2.5% of the total number of surgically treated colorectal cancers (3). This is not a very common complication; however it is

0% mortality in the elective surgery of the of tumors in the same locations (14).

Localization of the occlusive tumor does not influence the prognosis (16).

anastomosis, a Hartmann operation or a simple colostomy can be performed.

controversies regarding the treatment of such lesions.

and a further prophylactic dose of antibiotic is administered.

Skin threads are suppressed 7 to 10 days post operatively.

an upward colostomy or internal derivation is performed.

**2.7 Postoperative treatment** 

transit is restored.

**2.8 Personal experience** 

**2.9 Conclusion** 

primary anastomosis.

**3. Perforated CRC** 

Colorectal cancer can present emergently as a colonic perforation as a result of leakage of the hyperseptic content into the peritoneal cavity and subsequently causing localized or generalized peritonitis. The perforation can be produced in a juxtatumoral position or or at some distance from the tumor, the so-called diastatic perforation. It usually appears in large neoplasms which evolve over a longer period of time, being therefore advanced from a regional perspective. Diastatic perforation appears in left colon cancers which undergo complete stenosis and result in upwards colon distension. The vascularization of the cecum where the perforation occurs, results in the outflow of the hyperseptic stasis content into the peritoneal cavity with consecutive peritonitis. Juxtatumoral perforation appears most frequently in right colon cancers and causes an abscess which subsequently perforates into the free peritoneum.

Tumoral perforation appears in the advanced stages of the disease. In the study conducted by Masaichi Ogawa and his collaborators (18) it is shown that in 53% of cases the disease is in stage IV, while in 37% it is in stage IIIb and in 10% stage IIIa.

### **3.2 Presentation**

Patients are referred to the hospital showing signs of an acute surgical abdomen. Abdominal pain is intense and diffused with low blood pressure, cold cyanotic teguments, and altered general health state. The history taking reveals colon distress manifested as diarrhea alternating with constipation, weight loss and stools with blood, mucus and pus.

On exam, patients can show signs of septic shock, with general abdominal muscular contraction and peritoneal irritation. In the later stages they can present with a distended abdomen without intestinal peristalsis with an intensely altered general state and signs of shock.

In the case of intra peritoneal abscess which has not yet opened into the entire peritoneal cavity, signs of peritonitis are localized at the tumor level which may be palpated on exam. If the perforation has led to the formation of a retroperitoneal abscess, the patient usually presents with a septic state associated to subcutaneous emphysema and abdominal wall cellulites.

### **3.3 Diagnosis**

The diagnosis is mainly clinical and demands urgent surgical treatment.

Abdominal X-rays display pneumoperitoneum in the case of free perforation in the peritoneal cavity. Marked cecum distension can be discerned with diastatic perforation imminence even before its onset.

X-rays and abdominal CT scan show a consecutive intraperitoneal abscess in the blocked tumor perforation. Laboratory investigations reveal an important leukocytosis with potential signs of secondary renal failure from the emergent peritonitis.

### **3.4 Differential diagnosis**

The juxtatumoral perforation of the cecum with consecutive abscess must be distinguished from a gangrenous and blocked appendicitis. This situation is especially due to the fact that this form of appendicitis can be seen in the elderly patients. In addition to cancer of the cecum may present in this manner. The ultimate diagnosis can often be established only after the histopathological examination of the surgical resection piece.

Perforated cancer of the sigmoid colon must be differentiated from perforated sigmoid diverticulitis with abscess, which often presents with a similar clinical picture. In this case too, the final diagnosis is histopathological.

Retroperitoneal abscess following perforation of left or right colon cancer must be differentiated from a retroperitoneal abscesses of renal origin. This differentiation can be performed following imaging explorations which reveal renal modifications.

### **3.5 Preoperatory preparation**

The preoperative preparation needs to be short but thorough insofar as generalized peritonitis is concerned, so as not to delay the surgical intervention and miss the appropriate moment for surgical intervention. Shock therefore needs to be treatedand patients require a wide spectrum antibiotic prophylaxis, and finally basic preoperatory protocols (ECG, biochemistry, arterial blood gases, chest X-ray, etc).

### **3.6 Treatment**

Due to the neoplastic background on which the hyperseptic peritonitis occurs, any largescale surgical intervention resulting in anastomosis must be avoided as it is shown to have poor outcomes.

It is crucial for the treatment to be marked as high emergency. Together with the extended resections, this can improve the prognosis (19).

Treatment of the peritonitis mainly consists of abundant washing of the peritoneal cavity, multiple drains, and broad spectrum antibiotics.

The approach of the perforated tumor is different depending on the local situation. If it can be removedeasily, that can be done without an anastomosis, and instead through an upward terminal colostomy with closure of the remaining distal end (Hartmann type intervention) (20). If the tumor cannot be easily resected, a simple upwards derivative colostomy is performed or an ileostomy associated with the aforementioned peritonitis treatment. After the general condition of the patient improves, surgical intervention is performed and completed to remove the perforated tumor, if possible.

In case of diastatic perforation of the cecum, surgical treatment is a subtotal colectomy with ileostomy followed by the reconstruction of intestinal transit through an ileocolic or ileorectal anastomosis when the patient's condition improves.

### **3.7 Postoperative treatment**

In the postoperatory stage, the antibiotic treatment of peritonitis continues, as well as the hydroelectrolythic and acid-base rebalancing as and venous thrombosis. Drains and colostomies are monitored and drains should be discontinued when deemed appropriate.

An improved survival rate at 5 years is associated with administration of postoperative chemotherapy, compared with patients who did not receive this following release from hospital (21).

### **3.8 Prognosis**

82 Contemporary Issues in Colorectal Surgical Practice

X-rays and abdominal CT scan show a consecutive intraperitoneal abscess in the blocked tumor perforation. Laboratory investigations reveal an important leukocytosis with

The juxtatumoral perforation of the cecum with consecutive abscess must be distinguished from a gangrenous and blocked appendicitis. This situation is especially due to the fact that this form of appendicitis can be seen in the elderly patients. In addition to cancer of the cecum may present in this manner. The ultimate diagnosis can often be established only

Perforated cancer of the sigmoid colon must be differentiated from perforated sigmoid diverticulitis with abscess, which often presents with a similar clinical picture. In this case

Retroperitoneal abscess following perforation of left or right colon cancer must be differentiated from a retroperitoneal abscesses of renal origin. This differentiation can be

The preoperative preparation needs to be short but thorough insofar as generalized peritonitis is concerned, so as not to delay the surgical intervention and miss the appropriate moment for surgical intervention. Shock therefore needs to be treatedand patients require a wide spectrum antibiotic prophylaxis, and finally basic preoperatory protocols (ECG,

Due to the neoplastic background on which the hyperseptic peritonitis occurs, any largescale surgical intervention resulting in anastomosis must be avoided as it is shown to have

It is crucial for the treatment to be marked as high emergency. Together with the extended

Treatment of the peritonitis mainly consists of abundant washing of the peritoneal cavity,

The approach of the perforated tumor is different depending on the local situation. If it can be removedeasily, that can be done without an anastomosis, and instead through an upward terminal colostomy with closure of the remaining distal end (Hartmann type intervention) (20). If the tumor cannot be easily resected, a simple upwards derivative colostomy is performed or an ileostomy associated with the aforementioned peritonitis treatment. After the general condition of the patient improves, surgical intervention is performed and

In case of diastatic perforation of the cecum, surgical treatment is a subtotal colectomy with ileostomy followed by the reconstruction of intestinal transit through an ileocolic or

potential signs of secondary renal failure from the emergent peritonitis.

after the histopathological examination of the surgical resection piece.

performed following imaging explorations which reveal renal modifications.

**3.4 Differential diagnosis** 

too, the final diagnosis is histopathological.

biochemistry, arterial blood gases, chest X-ray, etc).

resections, this can improve the prognosis (19).

multiple drains, and broad spectrum antibiotics.

completed to remove the perforated tumor, if possible.

ileorectal anastomosis when the patient's condition improves.

**3.5 Preoperatory preparation** 

**3.6 Treatment** 

poor outcomes.

Prognosis of this complication is linked to the evolution and stage of tumor and to the severity of the peritonitis. In general, this complication carries an unfavorable prognosis, especially in case of diastatic perforation (22).

Mortality reaches 30 to 40% in cases of tumor perforation. In cases of diastatic perforation, mortality is between 50% and 68% (23), (24). If cases of death are excluded shortly after the intervention, the prognosis of perforated colorectal cancers is similar to that of unperforated cancers in the same stage (25).

### **4. Colorectal haemorrhagic cancers**

### **4.1 Introduction**

Hemorrhagic cancers are those cancers of the rectum and colon which manifest as colorectal bleeding. This is usually presents as melena for those cancers situated at the right colon level or as rectorrhagia with fresh blood for those situated in more distal positions, especially those situated at the recto-sigmoid level (1). Cancers that present as severe hemorrhage are rare; but they usually manifest through rectorrhagia and are extremely critical (26). Such cases require emergency surgery due to hemorrhage and the immediate goal of the treatment is obtaining hemostasis. Radical treatment of colorectal cancer is encouraged whenever possible.

### **4.2 History**

The patient is referred to a physician in order to determine the presence of blood in the stool, either as dark stool (melena), or as fresh blood. Symptoms usually appear in a patient with previous stool disturbances, with alternating diarrhea-constipation, weight loss over a couple of months and altered general condition. The patient also may have a history of abdominal pains often colicky-like. For recto-sigmoid cancers the patient can present with rectal tenesmus and pathological products in the stool (eg. mucus). Usually patients are pale and frail, showing signs of acute or chronic anemia. At the rectal examination, fecal occult blood may be detected.

### **4.3 Diagnosis**

In the presence of lower gastro-intestinal hemorrhage, colonoscopy is performed and highlights the presence of colorectal cancer with localization of the hemorrhagic source. Biopsies are collected for the histopathological diagnosis. Abdominal ultrasound and CT scan establishes the lesional abdominal record by emphasizing the local and regional extension of the lesion. Pulmonary radiologic exploration detects any eventual pulmonary disseminations of the colorectal cancer.

The TC99 scintigraphy has a reliability of 100% and a sensitivity of 91% in establishing the source of hemorrhage (27).

Biochemical and hematological explorations are compulsory for the preoperatory inventory. Microcytic hypochromic anemia is usually detected, requiring preoperatory correction with blood transfusion.

### **4.4 Differential diagnosis**

A differential diagnosis has to be made between lower and upper gastro-intestinal tract hemorrhage. Upper digestive hemorrhage originates above the ligament of Treitz and it is usually manifested through hematemesis and melena. If the hemorrhage is significant it can manifest itself as a rectorrhagia, but is usually associated with hematemesis. Emergency colonoscopy branches out the diagnosis. Apart from colorectal cancer there are other diseases which can evolve with rectorrhagia, for example ulcero-hemorrhagic rectocolitis, benign tumors which can cause bleeding, intestinal mesenteric infarct, intestinal invagination, etc. However, the clinical picture is different to that of colorectal cancer, as there can be present signs of peritonitis and shock (intestinal-mesenteric infarct) or of bowel obstruction (invagination). At the distal gastro-intestinal tract, the cause of rectorrhagia can be represented by hemorrhoids or anal fissure, which can be detected through anoscopy and rectal examination.

### **4.5 Preoperative treatment**

The preoperative assessment and treatment is usually performed as an emergency in order not to delay surgical intervention. Correction of anemia is necessary through transfusion of packed red blood cells, often rh- because of the emergent nature.

Electrolytes should be monitored and corrected as appropriate.

### **4.6 Treatment**

The objective is to remove the source of hemorrhage, i.e. the source of colorectal cancer. If possible, an intervention with radical aim is performed when the patient's general condition allows it.

Therefore, in right colon hemorrhagic cancers a right hemicolectomy is performed, while in left colon cancers a left hemicolectomy. In recto-sigmoid cancers a resection or rectum amputation is planned depending on the distance from the tumor to the anal margin.

There are situations when the cancer is in the advanced stages, making it impossible to be removed. In these cases a derivative process can be performed with anupward colostomy type or the colo-colonic or entero-colonic derivation thus putting the colon to rest in the hope that in the absence of local trauma represented by the fecal discharge, the hemorrhage will stop.

### **4.7 Postoperatory treatment**

Resuscitation procedures initiated at the pre operatory stage are continued with whole blood transfusions or packed red blood cells and prophylactic antibiotics aiming to correct the hemorrhagic shock.

The stoma and the surgical trauma are appropriately treated.

### **4.8 Results and prognosis**

These depend on the stage of evolution of the colorectal cancer and advanced forms with marked regional invasion have a poor prognosis.

### **5. Conclusions**

84 Contemporary Issues in Colorectal Surgical Practice

The TC99 scintigraphy has a reliability of 100% and a sensitivity of 91% in establishing the

Biochemical and hematological explorations are compulsory for the preoperatory inventory. Microcytic hypochromic anemia is usually detected, requiring preoperatory correction with

A differential diagnosis has to be made between lower and upper gastro-intestinal tract hemorrhage. Upper digestive hemorrhage originates above the ligament of Treitz and it is usually manifested through hematemesis and melena. If the hemorrhage is significant it can manifest itself as a rectorrhagia, but is usually associated with hematemesis. Emergency colonoscopy branches out the diagnosis. Apart from colorectal cancer there are other diseases which can evolve with rectorrhagia, for example ulcero-hemorrhagic rectocolitis, benign tumors which can cause bleeding, intestinal mesenteric infarct, intestinal invagination, etc. However, the clinical picture is different to that of colorectal cancer, as there can be present signs of peritonitis and shock (intestinal-mesenteric infarct) or of bowel obstruction (invagination). At the distal gastro-intestinal tract, the cause of rectorrhagia can be represented by hemorrhoids or anal fissure, which can be detected through anoscopy and

The preoperative assessment and treatment is usually performed as an emergency in order not to delay surgical intervention. Correction of anemia is necessary through transfusion of

The objective is to remove the source of hemorrhage, i.e. the source of colorectal cancer. If possible, an intervention with radical aim is performed when the patient's general condition

Therefore, in right colon hemorrhagic cancers a right hemicolectomy is performed, while in left colon cancers a left hemicolectomy. In recto-sigmoid cancers a resection or rectum amputation is planned depending on the distance from the tumor to the anal margin.

There are situations when the cancer is in the advanced stages, making it impossible to be removed. In these cases a derivative process can be performed with anupward colostomy type or the colo-colonic or entero-colonic derivation thus putting the colon to rest in the hope that in the absence of local trauma represented by the fecal discharge, the hemorrhage will stop.

Resuscitation procedures initiated at the pre operatory stage are continued with whole blood transfusions or packed red blood cells and prophylactic antibiotics aiming to correct

packed red blood cells, often rh- because of the emergent nature. Electrolytes should be monitored and corrected as appropriate.

source of hemorrhage (27).

**4.4 Differential diagnosis** 

blood transfusion.

rectal examination.

**4.6 Treatment** 

allows it.

**4.5 Preoperative treatment** 

**4.7 Postoperatory treatment** 

the hemorrhagic shock.

Fortunately, complicated colorectal cancers with significant hemorrhage are rare. They usually present with occult bleeding and chronic signs of anemia.. The advanced regional forms with severe hemorrhage from the necrosed tumor unfortunately have little therapeutic options and results are poor.

### **6. References**


**Part 4** 

**Postoperative Follow-Up** 

86 Contemporary Issues in Colorectal Surgical Practice

[12] Ansaloni L, Andersson RE, Bazzoli F, Catena F, Cennamo V, Di Saverio S, Fuccio L,

[14] Claudio Coco, Alessandro Verbo, Alberto Manno, Claudio Mattana, Marcello Covino,

[15] Zhang MS, Mao WZ, Zhou YB, Wang PG, Zhang BY. Surgical treatment and prognostic

[16] Frago R, Biondo S, Millan M, Kreisler E, Golda T, Fraccalvieri D, Miguel B, Jaurrieta E .

[17] Bevacizumab-induced bowel perforation.Sliesoraitis S, Tawfik B. J Am Osteopath

[18] Masaichi Ogawa, Michiaki Watanabe, Ken Eto, Takahiro Omachi, Makoto Kosuge, …

[19] Carraro PG, Segala M, Orlotti C, Tiberio G. Outcome of large-bowel perforation in patients with colorectal cancer. Dis Colon Rectum. 1998 Nov; 41(11):1421-6. [20] Meyer F, Grundmann RT. Hartmann's procedure for perforated diverticulitis and

[21] Min Sang Kim, Seung Woo Lim, Sung Jin Park, Geumhee Gwak, Keun Ho Yang, Byung

Case-Control Study. J Korean Soc Coloproctol: Vol. 26, No. 1, 69-75, 2010. [22] Khan S, Pawlak SE, Eggenberger JC, Lee CS, Szilagy EJ, Margolin DA. Acute colonic perforation associated with colorectal cancer. Am Surg. 2001 Mar; 67(3):261-4. [23] Peregudov SI, Sinenchenko GI, Kurygin AA, Pirogov AV. Experience in surgery of diastatic ruptures of the colon. Vestn Khir Im I I Grek. 2008; 167(3):49-53. [24] Renoux B, Herbault GF, Jean E. Diastatic perforations of the colon of neoplastic origin.

[25] .Zielinski MD, Merchea A, Heller SF, You YN. Emergency Management of Perforated

[26] Iwata T, Konishi K, Yamazaki T, Kitamura K, Katagiri A, Muramoto T, Kubota Y, Yano

Colon Cancers: How Aggressive Should We Be? Journal of Gastrointestinal

Y, Kobayashi Y, Yamochi T, Ohike N, Murakami M, Gokan T, Yoshikawa N, Imawari M. Right colon cancer presenting as hemorrhagic shock. World J

Apropos of 15 cases. J Chir (Paris). 1986 Nov; 123(11):644-50.

Gastrointest Pathophysiol. 2011 Feb 15; 2(1):15-8. [27] Schwartz S et al. Principles of Surgery. Ed I , Teora 2005.pp. 1066-1072

colorectal cancer. Dis Colon Rectum. 2012 Jan;55(1):72-8

surgery. Colorectal Dis 2011 Jun; 13(6):e116-22.

Surg (2005) 29: 1458–1464.

2011 Aug; 14(8):620-622.

Assoc. 2011 Jul;111(7):437-41.

Issue: 5, Pages: 1681-1684.

Surgery (Sep 2011).

Feb; 136(1):25-33. Epub 2011 Feb 18.

Jeekel H, Leppäniemi A, Moore E, Pinna AD, Pisano M, Repici A, Sugarbaker PH, Tuech JJ. Guidelenines in the management of obstructing cancer of the left colon: consensus conference of the world society of emergency surgery (WSES) and peritoneum and surgery (PnS) society. World J Emerg Surg. 2010 Dec 28;5:29. [13] Sasaki K, Kazama S, Sunami E, Tsuno NH, Nozawa H, Nagawa H, Kitayama J.One-

stage segmental colectomy and primary anastomosis after intraoperative colonic irrigation and total colonoscopy for patients with obstruction due to left-sided

Giorgio Pedretti, Luigi Petito, Gianluca Rizzo and Aurelio Picciocchi. Impact of Emergency Surgery in the Outcome of Rectal and Left Colon Carcinoma. World J

factors for obstructing left colorectal cancer. Zhonghua Wei Chang Wai Ke Za Zhi

Differences between proximal and distal obstructing colonic cancer after curative

Ken Hanyu, Lohta Noaki, Tetsuji Fujita, Katsuhiko Yanaga. Clinicopathological features of perforated colorectal cancer. Anticancer Research (2009) Volume: 29,

malignant left-sided colorectal obstruction and perforation. Zentralbl Chir. 2011

Noe Bae, Ki Hwan Kim, Sewhan Han, Hong Joo Kim, Young Duck Kim, Hong Yong Kim. Survival Rate and Prognostic Factors in Perforated Colorectal CancerPatients: A

### **Surveillance and Characteristics of Recurrence After Curative Resection for Colorectal Cancer**

Hirotoshi Kobayashi1,2 and Kenichi Sugihara2

*1Center for Minimally Invasive Surgery 2Department of Surgical Oncology Tokyo Medical and Dental University, Tokyo Japan* 

### **1. Introduction**

Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries.1 In developed counties, colorectal cancer is the second leading cause of cancer death in men and the third leading cause of cancer death in women.2 In developing countries, colorectal cancer is the fifth leading cause of cancer death in men and the sixth in women. Worldwide, colorectal cancer is the fourth leading cause of cancer death in men and the third in women.2

The most promising treatment for colorectal cancer is curative surgery. However, some patients recur after curative resection.3 In order to detect and treat recurrent tumors earlier, a post-operative surveillance after curative resection for colorectal cancer is in clinical use, although an optimal surveillance system for patients with curative resection for colorectal cancer is still uncertain.

In this chapter, we describe some topics concerning surveillance and characteristics of recurrence after curative resection for colorectal cancer as follows:


### **2. Historical review of surveillance after curative resection for colorectal cancer**

### **2.1 Randomized controlled study**

The consensus on the optimal surveillance schedule after curative resection for colorectal cancer has not been established. Six randomized controlled trials (RCT) were reported to validate the usefulness of intensive surveillance after curative resection for colorectal cancer (Table 1).4-9 In all RCTs, there were no differences in recurrence rate between patients with and without intensive follow-up. There was a description of time to recurrence after curative resection for colorectal cancer in three RCTs.4,5,7 Intensive surveillance led to earlier detection of recurrence in all three RCTs. As for curative resection rates of recurrent tumor, in three RCTs, intensive surveillance led to more frequent curative resection for recurrent tumor.4,7,9 On the other hand, in two RCTs, there were no differences in resection rates of recurrent tumor.5,6 Two RCTs disclosed the better survival in the intensive group,7,9 although the majority of RCTs failed to show a survival benefit of intensive surveillance after curative resection for colorectal cancer.4-6,8

### **2.2 Meta-analysis**

Although six RCTs have been conducted, all trials were underpowered or unsatisfactory. Therefore, three meta-analyses using the data of these RCTs evaluated the usefulness of intensive surveillance.10-12 There was no significant difference in recurrence rate between patients with intensive surveillance and those with non-intensive one. Renehan et al. reported that intensive surveillance led to earlier detection of recurrence after curative resection for colorectal cancer.12 Jeffery et al. clarified that intensive surveillance led to higher resection rate of recurrent tumor.11 In all meta-analyses, intensive surveillance improved survival after curative resection for colorectal cancer.

### **3. Characteristics of recurrence after curative resection for colorectal cancer**

The Japanese Society for Cancer of the Colon and Rectum (JSCCR) organized the study group on post-surgical surveillance after curative resection for colorectal cancer in 2003. The data were collected from 14 institutions which were the members of JSCCR. The recurrence rate after curative resection for colorectal cancer was investigated according to the TNM stage and the recurrence site.3 The data of 5,230 patients who underwent curative resection for colorectal cancer from 1991 to 1996 were collected. Among 5,230 patients, 3,583 had colon cancer and 1,647 had rectal cancer. Among these, 906 patients (17.3%) developed a recurrence during the median surveillance of 6.6 years. The characteristics of patients are shown in Table 2. The recurrence rate was significantly higher in patients with rectal cancer (24.3%) than in those with colon cancer (14.1%, p<0.0001).

### **3.1 Recurrence by TNM stage**

The recurrence rate in each stage was 3.7% in stage I, 13.3% in stage II, and 30.8% in stage III, respectively (p<0.0001). In each stage, the recurrence rate in patients with rectal cancer was higher than that in patients with colon cancer. The recurrence rates after curative resection for stage I, II, and III colon cancer were 2.7%, 12.1%, and 24.3%, respectively. Those after curative resection for stage I, II, and III rectal cancer were 5.7%, 16.7%, and 43.2%, respectively. The speed of recurrence in patients with stage I cancer was slow and constant (Figure 1a). On the other hand, the recurrence appeared rapidly within 3 years after curative resection for stage II and III colorectal cancer (Figure 1b and 1c). The cumulative appearance rates of recurrence at 3 years for stage I, II, and III were 68.6%, 76.9%, and 87.0%, respectively. Those at 5 years were 96.1%, 92.9%, and 97.8%, respectively. Recurrence after 5 years was rare for all three stages: 0.14% (2/1367), 0.94% (18/1912), and 0.67% (13/1951), respectively.

and without intensive follow-up. There was a description of time to recurrence after curative resection for colorectal cancer in three RCTs.4,5,7 Intensive surveillance led to earlier detection of recurrence in all three RCTs. As for curative resection rates of recurrent tumor, in three RCTs, intensive surveillance led to more frequent curative resection for recurrent tumor.4,7,9 On the other hand, in two RCTs, there were no differences in resection rates of recurrent tumor.5,6 Two RCTs disclosed the better survival in the intensive group,7,9 although the majority of RCTs failed to show a survival benefit of intensive surveillance

Although six RCTs have been conducted, all trials were underpowered or unsatisfactory. Therefore, three meta-analyses using the data of these RCTs evaluated the usefulness of intensive surveillance.10-12 There was no significant difference in recurrence rate between patients with intensive surveillance and those with non-intensive one. Renehan et al. reported that intensive surveillance led to earlier detection of recurrence after curative resection for colorectal cancer.12 Jeffery et al. clarified that intensive surveillance led to higher resection rate of recurrent tumor.11 In all meta-analyses, intensive surveillance

**3. Characteristics of recurrence after curative resection for colorectal cancer**  The Japanese Society for Cancer of the Colon and Rectum (JSCCR) organized the study group on post-surgical surveillance after curative resection for colorectal cancer in 2003. The data were collected from 14 institutions which were the members of JSCCR. The recurrence rate after curative resection for colorectal cancer was investigated according to the TNM stage and the recurrence site.3 The data of 5,230 patients who underwent curative resection for colorectal cancer from 1991 to 1996 were collected. Among 5,230 patients, 3,583 had colon cancer and 1,647 had rectal cancer. Among these, 906 patients (17.3%) developed a recurrence during the median surveillance of 6.6 years. The characteristics of patients are shown in Table 2. The recurrence rate was significantly higher in patients with rectal cancer

The recurrence rate in each stage was 3.7% in stage I, 13.3% in stage II, and 30.8% in stage III, respectively (p<0.0001). In each stage, the recurrence rate in patients with rectal cancer was higher than that in patients with colon cancer. The recurrence rates after curative resection for stage I, II, and III colon cancer were 2.7%, 12.1%, and 24.3%, respectively. Those after curative resection for stage I, II, and III rectal cancer were 5.7%, 16.7%, and 43.2%, respectively. The speed of recurrence in patients with stage I cancer was slow and constant (Figure 1a). On the other hand, the recurrence appeared rapidly within 3 years after curative resection for stage II and III colorectal cancer (Figure 1b and 1c). The cumulative appearance rates of recurrence at 3 years for stage I, II, and III were 68.6%, 76.9%, and 87.0%, respectively. Those at 5 years were 96.1%, 92.9%, and 97.8%, respectively. Recurrence after 5 years was rare for all three stages: 0.14% (2/1367), 0.94% (18/1912), and 0.67% (13/1951),

after curative resection for colorectal cancer.4-6,8

improved survival after curative resection for colorectal cancer.

(24.3%) than in those with colon cancer (14.1%, p<0.0001).

**3.1 Recurrence by TNM stage** 

respectively.

**2.2 Meta-analysis** 


Table 1. Trials concerning surveillance after curative resection for colorectal cancer


\* Characteristics of patients with relapse compared to those without relapse, \*\*Man-Whitney U test, \*\*\*chi-square test.

Table 2. Characteristics of patients

Fig. 1a. The cumulative appearance rate of recurrence after curative resection for stage I (a), stage II (b), and stage III (c) colorectal cancer.

Fig. 1b. The cumulative appearance rate of recurrence after curative resection for stage I (a), stage II (b), and stage III (c) colorectal cancer.

Male 559 (18.0) 2546 (82.0) 3105 NS\*\*\*

Colon 506 (14.1) 3077 (85.9) 3583 p<0.0001\*\*\*

Stage II 255 (13.3) 1657 (86.7) 1912 p<0.0001\*\*\*

Age 62 ± 11 63 ± 11 63 ± 11 NS\*\*

Female 347 (16.3) 1778 (83.7) 2125

Rectum 400 (24.3) 1247 (75.7) 1647

Stage I 51 (3.7) 1316 (96.3) 1367

Stage III 600 (30.8) 1351 (69.2) 1951 Median follow-up perio 3.5 ± 2.9 7.1 ± 3.1 6.6 ± 3.1 p<0.0001\*\* \* Characteristics of patients with relapse compared to those without relapse, \*\*Man-Whitney U test,

Fig. 1a. The cumulative appearance rate of recurrence after curative resection for stage I (a),

Fig. 1b. The cumulative appearance rate of recurrence after curative resection for stage I (a),

Number of patients 906 (17.3) 4324 (82.7) 5230

Gender

TNM stage

Primary tumor site

\*\*\*chi-square test.

Table 2. Characteristics of patients

stage II (b), and stage III (c) colorectal cancer.

stage II (b), and stage III (c) colorectal cancer.

Patients with relapse (%) Patients without relapse (%) Total P value\*

Fig. 1c. The cumulative appearance rate of recurrence after curative resection for stage I (a), stage II (b), and stage III (c) colorectal cancer.

An intensive surveillance program could be adopted in stage II and III patients for the first 3 years and less intensive program for the next 2 years. Patients with stage I colorectal cancer could be followed less intensively.

### **3.2 First recurrence site**

A study using autopsy reported that the most frequent metastatic site from colorectal cancer was the liver followed by the lung.13 This was consistent with our study (Table 3).3 The liver was the most frequent recurrent site after curative resection for colon cancer (7.0%). The second was the lung (3.5%). The local recurrence was most frequent after curative resection for rectal cancer (8.8%). The lung and the liver were the second and the third frequent metastatic sites. There was no difference in hepatic recurrence rate between patients with colon cancer and those with rectal cancer, while the pulmonary, local and anastomotic recurrence rates after curative resection for rectal cancer were significantly higher than those for colon cancer. In each recurrent site, approximately 80 to 90% of recurrence developed within 3 years (Figure 2). More than 95% of anastomotic recurrence was found within 3 years after curative resection for colorectal cancer (Figure 2d). In 5 years after curative resection for colorectal cancer, more than 95% of recurrence was found in each recurrent site (Table 4).

In this study, there was no patient with preoperative radiotherapy for rectal cancer. At present, the standard therapy for rectal cancer is total mesorectal excision with preoperative chemoradiotherapy in many countries.14-18 Six percent of the patients with preoperative combined modality therapy for rectal cancer followed by total mesorectal excision developed a recurrence over 5 years.19 In their study, of the 67 patients who developed recurrent disease, 4 (6%) had recurrent disease documented greater than 5 years following surgery. Three of these 4 patients had a distant recurrence, and 1 had both a local and distant recurrence. The recurrences were documented 61, 71, 76, and 96 months following curative rectal resection.

Therefore, the surveillance after 5 years might be necessary if patients receive radiotherapy or adjuvant chemotherapy.


\* Recurrence rates in patients with colon cancer compared to those with rectal cancer, \*\* chi-square test, \*\*\* Mann-Whitney U test

Table 3. Comparison of recurrence rates between patients with colon cancer and those with rectal cancer


Table 4. Recurrence rates by the initial recurrence site

Fig. 2a. The cumulative appearance rate of recurrence in liver (a), lung (b), local (c), anastomosis (d), and others (e).

Patients with relapse

Number of patients

First recurrence site

\*\*\* Mann-Whitney U test

First recurrence site % recurrence (observed

anastomosis (d), and others (e).

recurrences /5230)

Table 4. Recurrence rates by the initial recurrence site

rectal cancer

Gender

TNM stage

Colon (%) Rectum (%)

Male 306/2066 (14.8) 253/1039 (24.4) p<0.0001\*\* Female 200/1517 (13.2) 147/608 (24.2) p<0.0001\*\*

Stage I 24/891 (2.7) 27/476 (5.7) p = 0.0056\*\* Stage II 171/1410 (12.1) 84/502 (16.7) p = 0.0091\*\* Stage III 311/1282 (24.3) 289/669 (43.2) p<0.0001\*\*

Liver 252/3853 (7.0) 121/1647 (7.3) NS\*\* Lung 126/3583 (3.5) 124/1647 (7.5) p<0.0001\*\* Local 64/3583 (1.8) 145/1647 (8.8) p<0.0001\*\* Anastomotic 9/3583 (0.3) 13/1647 (0.8) p = 0.0052\*\* Others 130/3583 (3.6) 69/1647 (4.2) NS\*\*

\* Recurrence rates in patients with colon cancer compared to those with rectal cancer, \*\* chi-square test,

Table 3. Comparison of recurrence rates between patients with colon cancer and those with

Liver 7.1 (373) 87.9 94.1 98.7 Lung 4.8 (250) 77.7 88.8 94.8 Local 4.0 (209) 81.1 90.3 96.1 Anastomotic 0.4 (22) 95.5 95.5 95.5 Others 3.8 (199) 79.8 91.4 95.5

Fig. 2a. The cumulative appearance rate of recurrence in liver (a), lung (b), local (c),

Patients with relapse

*P* value\*

506/3583 (14.1) 400/1647 (24.3) p<0.0001\*\*

within 3 years within 4 years within 5 years

Cumulative appearance rate of recurrence (%)

Fig. 2b. The cumulative appearance rate of recurrence in liver (a), lung (b), local (c), anastomosis (d), and others (e).

Fig. 2c. The cumulative appearance rate of recurrence in liver (a), lung (b), local (c), anastomosis (d), and others (e).

Fig. 2d. The cumulative appearance rate of recurrence in liver (a), lung (b), local (c), anastomosis (d), and others (e).

Fig. 2e. The cumulative appearance rate of recurrence in liver (a), lung (b), local (c), anastomosis (d), and others (e).

#### **3.3 Survival**

According to the Japanese data, the 5-year overall survival rates in patients with stage I, II, and III colon cancer were 92.8%, 85.5%, and 76.2%, respectively (Figure 3a). Those in patients with stage I, II, and III rectal cancer were 92.2%, 84.6%, and 62.0%, respectively (Figure 3b).3 These outcomes seem to be better than those of the patients in the Surveillance, Epidemiology, and End Results (SEER) population-based data from 1992 to 2004. According to the SEER data, the 5-year survival rates in patients with stage I, T3N0, and T4N0 colon cancer were 76.3%, 66.7%, and 55.0%, respectively.20 Those in patients with stage III colon cancer varied from73.7% (T1-2N1a) to 12.9% (T4bN2b).

Fig. 3a. The overall survival curve after curative resection for cancer of the colon (a) and rectum (b).

Fig. 2e. The cumulative appearance rate of recurrence in liver (a), lung (b), local (c),

According to the Japanese data, the 5-year overall survival rates in patients with stage I, II, and III colon cancer were 92.8%, 85.5%, and 76.2%, respectively (Figure 3a). Those in patients with stage I, II, and III rectal cancer were 92.2%, 84.6%, and 62.0%, respectively (Figure 3b).3 These outcomes seem to be better than those of the patients in the Surveillance, Epidemiology, and End Results (SEER) population-based data from 1992 to 2004. According to the SEER data, the 5-year survival rates in patients with stage I, T3N0, and T4N0 colon cancer were 76.3%, 66.7%, and 55.0%, respectively.20 Those in patients with stage III colon

Fig. 3a. The overall survival curve after curative resection for cancer of the colon (a) and

anastomosis (d), and others (e).

cancer varied from73.7% (T1-2N1a) to 12.9% (T4bN2b).

**3.3 Survival** 

rectum (b).

Fig. 3b. The overall survival curve after curative resection for cancer of the colon (a) and rectum (b).

In terms of rectal cancer, the 5-year overall survival rates in Japanese patients with stage I, II, and III rectal cancer were 92.2%, 84.6%, and 62.0%, respectively. According to the SEER data, the 5-year observed survival rates in patients with stage I, T3N0, and T4N0 rectal cancer were 77.6%, 64.0%, and 50.5%, respectively.21 As for stage III rectal cancer, the 5-year observed survival rates varied from 75.7% (T1N1a) to 12.3% (T4bN2b).

In each stage, the prognosis of the Japanese patients with colorectal cancer was better than that of US patients. One of the possible reasons might be the difference of surveillance system after curative resection for colorectal cancer. The Japanese patients with curative resection for colorectal cancer usually receive more intensive surveillance to detect recurrence than the American patients. Another possible reason might be the difference of surgical technique. The Japanese surgeons usually perform central vascular ligation to dissect regional lymph node. Some European institutions adopt the similar technique called complete mesocolic excision with central ligation. Hohenberger et al. presented an excellent outcome of patients who underwent complete mesocolic excision with central ligation.22 However, most institutions in the Western countries do not adopt this technique.23

### **3.4 Resection for recurrence**

In our study, among the 906 patients with recurrence after curative resection for colorectal cancer, 379 (41.8&) underwent resection for recurrence with curative intent.3 The prognoses of patients with resection for recurrence were better than those without resection. The 5-year survival rates after initial colorectal surgery in patients with and without resection for hepatic, pulmonary, local, and anastomotic recurrence were 55% and 11% (p<0.0001), 68% and 13% (p<0.0001), 48% and 22% (P = 0.0002), and 53% and 0% (p = 0.0003), respectively (Figure 4). The 5-year survival rates after resection for hepatic, pulmonary, local, and anastomotic recurrence were 45%, 48%, 27%, and 33%, respectively.

Fig. 4a. The outcomes after initial colorectal surgery in patients with and without resection for recurrence of liver (A), lung (B), local (C), and anastomosis (D).

Fig. 4b. The outcomes after initial colorectal surgery in patients with and without resection for recurrence of liver (A), lung (B), local (C), and anastomosis (D).

Fig. 4a. The outcomes after initial colorectal surgery in patients with and without resection

Fig. 4b. The outcomes after initial colorectal surgery in patients with and without resection

for recurrence of liver (A), lung (B), local (C), and anastomosis (D).

for recurrence of liver (A), lung (B), local (C), and anastomosis (D).

Fig. 4c. The outcomes after initial colorectal surgery in patients with and without resection for recurrence of liver (A), lung (B), local (C), and anastomosis (D).

Fig. 4d. The outcomes after initial colorectal surgery in patients with and without resection for recurrence of liver (A), lung (B), local (C), and anastomosis (D).

### **3.5 Timing of recurrence**

Patients were classified into three groups according to the timing of recurrence (TR): TR≤1 year, 1<TR≤3 years, 3 years<TR. The earlier the hepatic, pulmonary, and local recurrence, the poorer the survival after initial colorectal surgery (Figure 5).24 If patients had resection for recurrence, there was no difference in survival after recurrence according to the timing of recurrence (Figure 6).

Fig. 5a. The overall survival curve after initial colorectal surgery according to the timing of recurrence. The later recurrence in liver (a), lung (b), and local (c) leads to the better survival.

Fig. 5b. The overall survival curve after initial colorectal surgery according to the timing of recurrence. The later recurrence in liver (a), lung (b), and local (c) leads to the better survival.

Patients were classified into three groups according to the timing of recurrence (TR): TR≤1 year, 1<TR≤3 years, 3 years<TR. The earlier the hepatic, pulmonary, and local recurrence, the poorer the survival after initial colorectal surgery (Figure 5).24 If patients had resection for recurrence, there was no difference in survival after recurrence according to the timing

Fig. 5a. The overall survival curve after initial colorectal surgery according to the timing of recurrence. The later recurrence in liver (a), lung (b), and local (c) leads to the better

Fig. 5b. The overall survival curve after initial colorectal surgery according to the timing of recurrence. The later recurrence in liver (a), lung (b), and local (c) leads to the better

**3.5 Timing of recurrence** 

of recurrence (Figure 6).

survival.

survival.

Fig. 5c. The overall survival curve after initial colorectal surgery according to the timing of recurrence. The later recurrence in liver (a), lung (b), and local (c) leads to the better survival.

Fig. 5d. The overall survival curve after initial colorectal surgery according to the timing of recurrence. The later recurrence in liver (a), lung (b), and local (c) leads to the better survival.

Fig. 6a. If the patients underwent curative resection for recurrence, the outcomes after recurrence were irrespective of the timing of recurrence.

Fig. 6b. If the patients underwent curative resection for recurrence, the outcomes after recurrence were irrespective of the timing of recurrence.

Fig. 6a. If the patients underwent curative resection for recurrence, the outcomes after

Fig. 6b. If the patients underwent curative resection for recurrence, the outcomes after

recurrence were irrespective of the timing of recurrence.

recurrence were irrespective of the timing of recurrence.

Fig. 6c. If the patients underwent curative resection for recurrence, the outcomes after recurrence were irrespective of the timing of recurrence.

Fig. 6d. If the patients underwent curative resection for recurrence, the outcomes after recurrence were irrespective of the timing of recurrence.

### **4. Surveillance tools after curative resection for colorectal cancer**

In our study, the combination of symptoms, physical examination, and tumor marker detected the majority of recurrence in all sites except for lung (Table 5).3 In this section, the evidence for usefulness of each surveillance tool is discussed.


\*FI: First indicator

\*\*Symptoms include anal pain, anal bleeding, abdominal pain, and so on \*\*\*CS: Colonoscopy

Table 5. Rate of first indicator for recurrence

### **4.1 History and physical examination**

It is not rare that patients have a symptom at the time of recurrence after curative resection for colorectal cancer. According to the result of RCTs, 16% to 66% of patients had some sort of symptom.4,5 Therefore, periodical clinical visits seem to be important to detect a recurrence after curative resection for colorectal cancer. On the other hand, Ohlsson et al. reported that it was rare to detect a resectable recurrent tumor only history and physical examination.6

### **4.2 CEA**

104 Contemporary Issues in Colorectal Surgical Practice

\*FI: First indicator

\*\*\*CS: Colonoscopy

\*\*Symptoms include anal pain, anal bleeding, abdominal pain, and so on

First recurrence site

A:

Symptoms\*\*

B: Physical examination

C: Tumor marker

A + B + C Liver imaging

Chest x-ray

CT CS\*\*\* Others Unknown

3.8

Liver (n = 373)

Rate of FI\* (%)

 3.2 1.6 46.6 51.5 43.4

1.3

Lung (n = 250)

Rate of FI\* (%)

 6.8 1.6 26.4 34.8 48.4

10.4

2.8 3.6

18.2

6.7 2.9

1

18.2

9.1

4.5

18.6

5.5

6

Local (n = 209)

Rate of FI\* (%)

 27.2 20.6 23.4 71.3

Anastomotic (n = 22)

Rate of FI\* (%)

 13.6 36.4 18.2 68.2

Others (n = 199)

Rate of FI\* (%)

 19.6

8.5

41.7

69.8

Table 5. Rate of first indicator for recurrence

Carcinoembryonic antigen (CEA) is most widely used as tumor marker for colorectal cancer. The serum CEA level was high in the majority of patients with recurrence after curative resection for colorectal cancer.25 Especially, 80% of patients with hepatic recurrence from colorectal cancer had higher serum CEA levels.25 Graham et al. reported that serum CEA measurement was the most useful and economical surveillance tool to detect recurrence after curative resection for colorectal cancer.26 Therefore, serum CEA test was recommended as a surveillance tool after curative resection for colorectal cancer.10

### **4.3 Chest X-ray**

It is controversial to use chest x-ray as a surveillance tool to detect recurrence after curative resection for colorectal cancer. Since chest x-ray can detect resectable pulmonary metastasis with probability of 1%,26,27 it is not recommended to use chest x-ray as a surveillance tool in many institutions. On the other hand, Ike et al. reported the good outcomes of 42 patients with curative resection for pulmonary recurrence which was detected by the combination of serum CEA test of every 2 months and chest x-ray of every 6 months.28 The 5-year survival rate after curative resection for pulmonary recurrence was 63.7%.

### **4.4 CT scans**

Howell et al. reported that annual computed tomography (CT) scan could detect 87.5% of liver metastases at an asymptomatic stage,29 whereas, in total, only 2 cases out of 157 (1.3%) underwent curative resection for liver metastases. An RCT conducted by Schoemaker et al. clarified that abdominal CT scan increased the detection rate of liver metastases, although there was no difference in resection rate between the groups with and without CT scan.8 On the other hand, the UK group reported the usefulness of serum CEA measurement and CT scan in the surveillance of patients after adjuvant chemotherapy for colorectal cancer.30 In their study, among 530 patients with stage II and III colorectal cancer, 154 had recurrence after adjuvant chemotherapy. Recurrences were detected by symptoms (n = 65), CEA (n = 45), CT (n = 49), and others (n = 9). The CT-detected group had a better survival compared with the symptomatic group (P =.0046).

Intensive surveillance after curative resection for colorectal cancer was not adopted in Western countries.31,32 However, since the results of meta-analyses revealed that intensive surveillance after curative resection for colorectal cancer contributed to better outcomes, routine use of CT scans has been recommended.33,34

### **4.5 PET scans**

The usefulness of positron-emission tomography (PET) in the detection of recurrence after curative resection for colorectal cancer is uncertain. Sobhani et al. reported a clinical trial that randomly assigned 130 patients with curative resection for colorectal cancer to the conventional surveillance group (periodic serum tumor marker, ultrasound, chest x-ray, and CT scans) and the PET-additional group.35 The PET scans were performed in 9 and 15 months after surgery. Recurrences were detected after a shorter time (12.1 vs 15.4 months) in the PET group. Moreover, recurrences were more frequently cured by surgery (R0) in the PET group. The usefulness of PET scans in the detection of recurrence after curative resection for colorectal cancer should be clarified in a large-scale study.

### **4.6 Colonoscopy**

Since the anastomotic recurrence rate after colectomy is low, the usefulness of periodical colonoscopy to detect anastomotic recurrence is skeptical.36 On the other hand, since the anastomotic recurrence rate after resection for rectal cancer is higher than that after resection for colon cancer, several studies reported the adequacy of periodical colonoscopy to detect anastomotic recurrence after surgery.31,37 At the same time, colonoscopy can find metachronous adenoma and cancer in the colon and rectum. Metachronous lesions develop in 1.5 to 3% of patients in the first 5 years after colorectal surgery.8,27,38-42 In Japan, the colonoscopy is usually performed one year after colorectal surgery and thereafter every two years. If total colonoscopy cannot be performed preoperatively because of the stenosis, it is recommended that the first colonoscopy should be performed three to six months after colorectal surgery.

### **5. Recommended surveillance after curative resection for colorectal cancer from ESMO, ASCO, and JSCCR**

Both previous and present guidelines for surveillance after curative resection for colorectal cancer from ASCO and ESMO are shown in Table 6.31,33,34,43 Previously, neither ASCO nor ESMO recommended the intensive surveillance after curative resection for colorectal cancer, because most RCTs failed to show the prognostic significance of intensive surveillance.4-8 However, since three meta-analyses showed the effectiveness of intensive surveillance, these guidelines changed their attitude toward surveillance after curative resection for colorectal cancer. At present, both societies recommend periodical serum CEA measurement and CT. Periodical colonoscopy to detect metachronous adenoma and cancer is also recommended.

In Japan, JSCCR published the first edition of guidelines for the treatment of colorectal cancer in 2005 and the second edition in 2009. The Japanese institutions adopted more intensive surveillance to detect recurrence after curative resection for colorectal cancer. The recommended surveillance schedule in the Japanese guidelines is shown in the Table 7.

On the other hand, the optimal schedule and modality to detect recurrence after curative resection for colorectal cancer are still uncertain. These issues should be clarified by RCTs in future.

The usefulness of positron-emission tomography (PET) in the detection of recurrence after curative resection for colorectal cancer is uncertain. Sobhani et al. reported a clinical trial that randomly assigned 130 patients with curative resection for colorectal cancer to the conventional surveillance group (periodic serum tumor marker, ultrasound, chest x-ray, and CT scans) and the PET-additional group.35 The PET scans were performed in 9 and 15 months after surgery. Recurrences were detected after a shorter time (12.1 vs 15.4 months) in the PET group. Moreover, recurrences were more frequently cured by surgery (R0) in the PET group. The usefulness of PET scans in the detection of recurrence after curative

Since the anastomotic recurrence rate after colectomy is low, the usefulness of periodical colonoscopy to detect anastomotic recurrence is skeptical.36 On the other hand, since the anastomotic recurrence rate after resection for rectal cancer is higher than that after resection for colon cancer, several studies reported the adequacy of periodical colonoscopy to detect anastomotic recurrence after surgery.31,37 At the same time, colonoscopy can find metachronous adenoma and cancer in the colon and rectum. Metachronous lesions develop in 1.5 to 3% of patients in the first 5 years after colorectal surgery.8,27,38-42 In Japan, the colonoscopy is usually performed one year after colorectal surgery and thereafter every two years. If total colonoscopy cannot be performed preoperatively because of the stenosis, it is recommended that the first colonoscopy should be performed three to six months after

**5. Recommended surveillance after curative resection for colorectal cancer** 

Both previous and present guidelines for surveillance after curative resection for colorectal cancer from ASCO and ESMO are shown in Table 6.31,33,34,43 Previously, neither ASCO nor ESMO recommended the intensive surveillance after curative resection for colorectal cancer, because most RCTs failed to show the prognostic significance of intensive surveillance.4-8 However, since three meta-analyses showed the effectiveness of intensive surveillance, these guidelines changed their attitude toward surveillance after curative resection for colorectal cancer. At present, both societies recommend periodical serum CEA measurement and CT. Periodical colonoscopy to detect metachronous

In Japan, JSCCR published the first edition of guidelines for the treatment of colorectal cancer in 2005 and the second edition in 2009. The Japanese institutions adopted more intensive surveillance to detect recurrence after curative resection for colorectal cancer. The recommended surveillance schedule in the Japanese guidelines is shown in the Table 7.

On the other hand, the optimal schedule and modality to detect recurrence after curative resection for colorectal cancer are still uncertain. These issues should be clarified by RCTs in

resection for colorectal cancer should be clarified in a large-scale study.

**4.5 PET scans** 

**4.6 Colonoscopy** 

colorectal surgery.

future.

**from ESMO, ASCO, and JSCCR** 

adenoma and cancer is also recommended.


Table 6. Recommended guidelines from ASCO and ESMO

•Stage I – Stage III

°Omissible in Stage I and Stage II

Table 7. Surveillance schedule recommended by JSCCR

### **6. Summary**

108 Contemporary Issues in Colorectal Surgical Practice

•Stage I – Stage III

°Omissible in Stage I and Stage II

Table 7. Surveillance schedule recommended by JSCCR

Colon cancer Clinical visit CEA and CA19-9

Chest CT Abdominal CT

Colonoscopy

Rectal cancer Clinical visit CEA and CA19-9

Digital examination

Chest CT Abdominal and pelvic CT

Colonoscopy

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### **7. Reference**


[10] Figueredo A, Rumble RB, Maroun J, et al. Follow-up of patients with curatively resected

[11] Jeffery GM, Hickey BE, Hider P. Follow-up strategies for patients treated for nonmetastatic colorectal cancer. Cochrane Database Syst Rev 2002:CD002200. [12] Renehan AG, Egger M, Saunders MP, O'Dwyer ST. Impact on survival of intensive

[13] Weiss L, Grundmann E, Torhorst J, et al. Haematogenous metastatic patterns in colonic carcinoma: an analysis of 1541 necropsies. J Pathol 1986;150:195-203. [14] Randomised trial of surgery alone versus surgery followed by radiotherapy for mobile

[15] Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish

[16] Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined

[17] Adjuvant radiotherapy for rectal cancer: a systematic overview of 8,507 patients from 22

[18] Camma C, Giunta M, Fiorica F, Pagliaro L, Craxi A, Cottone M. Preoperative radiotherapy for resectable rectal cancer: A meta-analysis. Jama 2000;284:1008-15. [19] Guillem JG, Chessin DB, Cohen AM, et al. Long-term oncologic outcome following

[20] Gunderson LL, Jessup JM, Sargent DJ, Greene FL, Stewart AK. Revised TN

[21] Gunderson LL, Jessup JM, Sargent DJ, Greene FL, Stewart A. Revised tumor and node

[23] West NP, Hohenberger W, Weber K, Perrakis A, Finan PJ, Quirke P. Complete

[24] Kobayashi H, Mochizuki H, Morita T, et al. Timing of relapse and outcome after

[25] McCall JL, Black RB, Rich CA, et al. The value of serum carcinoembryonic antigen in

results and rectal pooled analysis outcomes. J Clin Oncol 2010;28:256-63. [22] Hohenberger W, Weber K, Matzel K, Papadopoulos T, Merkel S. Standardized surgery

and outcome. Colorectal Dis 2009;11:354-64; discussion 64-5.

advanced rectal cancer. Ann Surg 2005;241:829-36; discussion 36-8.

follow up after curative resection for colorectal cancer: systematic review and meta-

cancer of the rectum. Medical Research Council Rectal Cancer Working Party.

with total mesorectal excision for resectable rectal cancer. N Engl J Med

preoperative combined modality therapy and total mesorectal excision of locally

categorization for colon cancer based on national survival outcomes data. J Clin

categorization for rectal cancer based on surveillance, epidemiology, and end

for colonic cancer: complete mesocolic excision and central ligation--technical notes

mesocolic excision with central vascular ligation produces an oncologically superior specimen compared with standard surgery for carcinoma of the colon. J

curative resection for colorectal cancer: a Japanese multicenter study. Dig Surg

predicting recurrent disease following curative resection of colorectal cancer. Dis

colorectal cancer: a practice guideline. BMC Cancer 2003;3:26.

analysis of randomised trials. BMJ 2002;324:813.

Rectal Cancer Trial. N Engl J Med 1997;336:980-7.

randomised trials. Lancet 2001;358:1291-304.

Lancet 1996;348:1610-4.

2001;345:638-46.

Oncol 2010;28:264-71.

Clin Oncol 2010;28:272-8.

Colon Rectum 1994;37:875-81.

2009;26:249-55.


### **Difficult Infected Wound After Colorectal Surgery**

Prem Rathore *The Townsville Hospital, James Cook University, Queensland Australia* 

### **1. Introduction**

112 Contemporary Issues in Colorectal Surgical Practice

[42] Ringland CL, Arkenau HT, O'Connell DL, Ward RL. Second primary colorectal

[43] ESMO Minimum Clinical Recommendations for diagnosis, adjuvant treatment and

follow-up of colon cancer. Ann Oncol 2001;12:1053-4.

Oncology/ESMO 2010;21:92-7.

cancers (SPCRCs): experiences from a large Australian Cancer Registry. Annals of oncology : official journal of the European Society for Medical

> Surgical site infection (SSI) is a well known and commonly encountered scenario following major colorectal resection and has been documented as being a potentially morbid and costly complication.

> Surgical wounds in normal, healthy individuals heal through an orderly sequence of physiologic events that include inflammation, epithelialisation, fibroplasia, and maturation. Mechanical failure or failure of wound healing at the surgical site can lead to disruption of the closure leading to seroma, hematoma, wound dehiscence or hernia. Other complications include surgical site infection and nerve injury.

> For this reason, of late, emphasis has been placed on more efficient management of these patients including early recognition, and prompt treatment with a view to improve patient outcomes which are measured both in terms of postoperative morbidity, prolonged hospital stay and by extension an increased demand on finite hospital resources1.

> However, there has been wide discrepancy in the reported incidence of incisional SSI following colorectal surgery, ranging from 3 to 30%(1). Additionally, there has been no clear consensus on the risk factors contributing to SSI following colorectal surgery, which has limited the data's value to surgeons involved in quality improvement programs hoping to address specific variables that could reduce this risk.

> In this era of managed care organizations where patients expect short hospital stay and onestage resections are becoming more frequent, peri operative assessment of risk factors for wound infection should be intensified for the patient.

> Surgical site infections (SSI) are the third most common hospital-acquired infection and account for 14% to 16% of all such infections. However, in surgical patients, SSI is the leading cause of hospital-acquired infection2,3. Similar incidence of SSI has been documented by various studies in patients after colorectal surgery.

> The National Nosocomial Infection Surveillance system surveys all colorectal surgeries together, without differentiating the type of colorectal surgery performed. The outcome of their survey showed rectal surgery may have a higher risk for SSI, and identifying risk factors that are more specific to this procedure would be a better indicator to predict the possibility of SSI.

Several reports have described the substantial cost of these infections in terms of attributable mortality,3 increased morbidity measured as increased postoperative hospital length of stay, and increased hospital costs.

### **2. Risk factors**

Various studies have identified multiple risk factors and other associations which have a direct bearing on the incidence of these infections.



Table 1. Patient Related Risk Factors for Surgical Site Infection 4

c. **Technique related risk factors for surgical site infection4** *(Table 2)*: Various surgical related factors affect wound healing differently. This includes both pre surgical patient preparation and post operative care. Intra operative procedures including the surgical techniques like excessive use of electrocautery, poor haemostasis and tissue trauma can adversely affect wound healing as can the length of the surgery. Insertion and duration of intra abdominal drains remains a controversial point.


Table 2. Technique Related Risk Factors For Surgical Site Infection 4

Several reports have described the substantial cost of these infections in terms of attributable mortality,3 increased morbidity measured as increased postoperative hospital length of stay,

Various studies have identified multiple risk factors and other associations which have a

a. **Type of surgery:** Timing of the surgical procedure does not significantly predispose or preclude wound infections as it occurs in patients who have undergone both emergency

b. **Patient related risk factors for surgical site infection**<sup>4</sup> *(Table 1)*: This group of risk factors have a significant impact on the incidence of surgical site infection. Included in this group are pre-existing conditions like diabetes and cardiovascular disease. Patients nutritional status – both malnutrition and obesity and life style habits like smoking can cause significant impact on post-operative wound. Prior medical history of surgery,

and increased hospital costs.

direct bearing on the incidence of these infections.

surgery as well as those that had an elective procedure.

irradiation or cancer also adversely effect wound healing.

1. Diabetes 2. Obesity

5. Smoking 6. Cancer

Table 1. Patient Related Risk Factors for Surgical Site Infection 4

of intra abdominal drains remains a controversial point.

Table 2. Technique Related Risk Factors For Surgical Site Infection 4

1. Use of electrocautery

4. Skin antisepsis 5. Preoperative shaving 6. Preoperative skin prep 7. Duration of operation 8. Antimicrobial prophylaxis

2. Closure of subcutaneous tissue 3. Duration of surgical scrub

3. Immunosuppression 4. Cardiovascular disease

7. Previous surgery 8. Malnutrition and 9. Prior irradiation

c. **Technique related risk factors for surgical site infection4** *(Table 2)*: Various surgical related factors affect wound healing differently. This includes both pre surgical patient preparation and post operative care. Intra operative procedures including the surgical techniques like excessive use of electrocautery, poor haemostasis and tissue trauma can adversely affect wound healing as can the length of the surgery. Insertion and duration

> 9. Operating room ventilation 10. Inadequate sterilisation of

11. Foreign material in the surgical site

14. Failure to obliterate dead space

instruments

12. Surgical drains 13. Poor haemostasis

15. Tissue trauma

**2. Risk factors** 

d. **Factors associated with increased risk of fascial disruption5** *(Table 3)*: Multiple factors can increase the changes of loss of integrity of the fascia and largely relate to patient factors including patients' premorbid and associated medical conditions as does patient demographics.


Table 3. Factors associated with increased risk of fascial disruption

### **3. Classification of abdominal wound infection**

Surgical wound infection can be classified into different types based on various criteria6.

	- 1. **Superficial incisional surgical site infection**: Involves skin and subcutaneous fat (Image 1).
	- 2. **Deep incisional surgical site infection**: Involves rectus sheath and preperitoneal space (Image 2).
	- 3. **Organ / space surgical site infection**: Involves intraperitoneal compartment and intra abdominal organs (Image 3).

Fig. 1.

	- 1. **Clean**
	- 2. **Clean contaminated**
	- 3. **Contaminated**
	- 4. **Dirty**

Studies have shown an association between the type of wound and the incidence of surgical site infection (Table 4):


Table 4. Wound Classification and Risk for Surgical Site Infection

### **4. Clinical manifestation and diagnosis**

As with infection anywhere, surgical site infections present with localized erythema, induration, warmth, and pain at the incision site. Purulent wound drainage and separation of the wound may occur.

Some patients will have systemic evidence of their infection such as fever and leukocytosis.

Image 1. Superficial incisional surgical site infection showing skin and subcutaneous fat involvement.

Studies have shown an association between the type of wound and the incidence of surgical

**Classification Examples Incidence of SSI (%)** 

infected spaces < 2

mechanical and antibiotic) 5-15

minor spillage), drainage of infected spaces 15-30

As with infection anywhere, surgical site infections present with localized erythema, induration, warmth, and pain at the incision site. Purulent wound drainage and separation

Some patients will have systemic evidence of their infection such as fever and leukocytosis.

Image 1. Superficial incisional surgical site infection showing skin and subcutaneous fat

>30

b. Based on the type of wound they are classified as:

Clean Elective surgery without violation of the gut or

Contaminated Emergent bowel surgery (unprepared bowel,

Table 4. Wound Classification and Risk for Surgical Site Infection

**4. Clinical manifestation and diagnosis** 

Elective bowel surgery (prepared bowel,

Grossly contaminated traumatic wounds, significant intestinal spillage, grossly infected and devitalized tissue (necrotizing infection)

1. **Clean** 

4. **Dirty** 

Clean

Dirty

contaminated

of the wound may occur.

involvement.

site infection (Table 4):

2. **Clean contaminated**  3. **Contaminated** 

Image 2. Deep incisional surgical site infection involving rectus sheath and preperitoneal space.

Image 3. Organ surgical site infection shown as an open abdomen with Involvement of the peritoneal cavity and omentum managed by mesh placement.

Diagnosis of surgical site infection is largely clinical.

Role of imaging is limited to those patients in whom there is a clinical suspicion of deep space infections or collections. Of the imaging modalities, Computed Tomography is the preferred modality for assessment.

Ultrasound may have a limited role in assessing deep space infections but can evaluate collections related to superficial wounds, particularly, if the clinical evaluation is difficult or inconclusive.

### **5. Complication of SSI**

In addition to the complications related directly to the wound, patients with SSI can have other complications based on their pre surgical risk factors and co morbidities that can adversely affect their long term outcome and prolong their convalescence.

These complications have been well documented and researched and include long hospital stay, increasing morbidity, SIRS – Sepsis – MOF and even death.

### **5.1 Management**

Recent studies have shown the strong influence of the various risk factors that results in an increase in the incidence of surgical site infection. Thus, there has been a shift in the approach to the management of these patients with emphasis being placed on prophylaxis.

### **5.1.1 Prophylaxis**


Evidence category IA - Well designed studies


Evidence category IB - Good evidence and expert consensus

1. Control glucose levels in diabetic patients and avoid peri operative hyperglycemia

In addition to the complications related directly to the wound, patients with SSI can have other complications based on their pre surgical risk factors and co morbidities that can

These complications have been well documented and researched and include long hospital

Recent studies have shown the strong influence of the various risk factors that results in an increase in the incidence of surgical site infection. Thus, there has been a shift in the approach to the management of these patients with emphasis being placed on prophylaxis.

 Adequately identifying and correcting the various systemic co-morbidities thus optimising the pre-operative status and reducing the pre-operative risk for SSI. - This has shown to be as important as post-operative and intra-operative care. It includes ensuring adequate control of diabetes and assessment and correction of



 Optimising surgical techniques at various levels starting with adequate patient preparation for surgery which include antibacterial shower on the day of surgery,



 Reducing tissue trauma during surgery by gentle dissection of tissue, cautious use of electrocautery and saline wash-out of the wound has shown a lower incidence of SSI. Reducing operative time and appropriate use of intrabdominal drains also reduces the

1. Cancel elective surgery if the patient has an infection at or remote from the surgical site

4. If it is necessary to remove hair, use clippers, not shaving, immediately before operation

1. Control glucose levels in diabetic patients and avoid peri operative hyperglycemia

2. Achieve maximal subcutaneous concentration of peri operative antibiotics 3. Maintain prophylactic antibiotics for only a few hours after closing incisions

patients have shown to favourably improve surgical outcome.

using suture length to wound length ratio of 4 to 1.

**Best practices for preventing surgical site infections 7 :** 

Evidence category IB - Good evidence and expert consensus

Evidence category IA - Well designed studies

adversely affect their long term outcome and prolong their convalescence.

stay, increasing morbidity, SIRS – Sepsis – MOF and even death.

cardiovascular problems pre-operatively.

**5. Complication of SSI** 

**5.1 Management** 

**5.1.1 Prophylaxis** 

the risk of SSI.

intervals.

risk.

shaving of the site on table.


### **5.1.2 Definitive management**

Definitive management of SSI depends on the type of infection.

### **5.1.2.1 Superficial incisional surgical site infection**

Infected wounds are opened, explored, drained, irrigated, débrided and dressed open.

If fascial disruption is suspected, drainage should be performed in the operating room.

The severity of the infection determines the need for antibiotic therapy. Once the infection has cleared and granulation tissue is apparent, the wound can be closed secondarily.

### **5.1.2.2 Deep incisional surgical site infection**

### **Fascial dehiscence:**

Fascial disruption is due to abdominal wall tension overcoming tissue or suture strength, or knot security as a result of infection or collection. It can occur either early or late in the postoperative period and can involve a portion of the incision (i.e, partial dehiscence) or the entire incision (i.e, complete fascial dehiscence).

The incidence of fascial disruption ranges from 0.4 to 3.5 % depending upon the type of surgery performed. Despite improved perioperative care and stronger suture materials, the incidence and morbidity of fascial dehiscence is largely unchanged.

When fascial disruption is suspected, wound exploration should be performed in the operating room. Complete fascial dehiscence is associated with a mortality rate of 10% and is a surgical emergency. At the bedside, a moist dressing is placed over the wound and a binder placed around the patient's abdomen to prevent evisceration on the way to the operating room.

Once opened, the wound is thoroughly debrided. Treatment options include either using VAC dressing or mass closure. Mass closure done with continuous or retention nonabsorbable sutures is an option only if the intra-abdominal pressure and tissue oedema intraoperatively is not high. In such cases VAC dressing is the preferred treatment.

### **Prevention**

Meta-analyses related to abdominal fascial closure suggest an optimal technique for closure of abdominal surgical wounds includes(8,9):


### **5.1.2.3 Organ/Space surgical site infection**

One of the critical decisions in the surgical treatment of patients with severe peritonitis is whether to use an open-abdomen or a closed-abdomen technique.

### **Closed abdomen technique**

The goal of the closed-abdomen technique is to provide definitive surgical treatment at the initial operation which saves the patient from repetitive trauma of anaesthesia and surgery.

Opting for this technique should be judicious in an unstable patient.

### **Open abdomen technique**

VAC dressing and temporary closure with sponge or mesh are types of open abdomen techniques which are valuable tools for the management of patients with acidosis, hypothermia and coagulopathy. This is a very resource-intensive decision.

The goal of the open-abdomen technique is to provide easy, direct access to the affected area. Source control is achieved through repeated reoperations or through open packing of the abdomen. This technique may be well suited for initial damage control in extensive peritonitis.

The open-abdomen technique should also be considered in patients who are at high risk for the development of abdominal compartment syndrome (eg, patients with intestinal distension, extensive abdominal wall and intra-abdominal organ edema), because attempts to perform primary fascial closure under significant tension in these circumstances are associated with an increased incidence of multiple organ failure (eg, renal, respiratory), necrotizing abdominal wall infections, anastomotic leak, entero-cutaneous fistula and mortality.

Temporary closure of the abdomen to prevent herniation and contamination can be achieved by using various materials (Table 5):


absorbable sutures is an option only if the intra-abdominal pressure and tissue oedema

Meta-analyses related to abdominal fascial closure suggest an optimal technique for closure

One of the critical decisions in the surgical treatment of patients with severe peritonitis is

The goal of the closed-abdomen technique is to provide definitive surgical treatment at the initial operation which saves the patient from repetitive trauma of anaesthesia and surgery.

VAC dressing and temporary closure with sponge or mesh are types of open abdomen techniques which are valuable tools for the management of patients with acidosis,

The goal of the open-abdomen technique is to provide easy, direct access to the affected area. Source control is achieved through repeated reoperations or through open packing of the abdomen. This technique may be well suited for initial damage control in extensive peritonitis. The open-abdomen technique should also be considered in patients who are at high risk for the development of abdominal compartment syndrome (eg, patients with intestinal distension, extensive abdominal wall and intra-abdominal organ edema), because attempts to perform primary fascial closure under significant tension in these circumstances are associated with an increased incidence of multiple organ failure (eg, renal, respiratory), necrotizing abdominal

Temporary closure of the abdomen to prevent herniation and contamination can be

1. Self-adhesive impermeable membrane dressings using sponge and opsite. Though it is in inexpensive and easy to apply, the major disadvantage is difficulty in maintaining

2. Mesh like Vicryl and Dexon made of absorbable material can be directly applied over bowel, but the drawbacks are loss of strength in the presence of infection and higher

wound seal. In addition, there is loss of large volumes of extracellular fluid.

intraoperatively is not high. In such cases VAC dressing is the preferred treatment.

Use of mass closure to incorporate all layers of the abdominal wall (except skin)

**Prevention**

of abdominal surgical wounds includes(8,9):

**5.1.2.3 Organ/Space surgical site infection** 

Use of #1 or #2 delayed absorbable monofilament suture

 Use of a suture length to wound length ratio of 4 to 1 Use of non-strangulating tension on the suture.

whether to use an open-abdomen or a closed-abdomen technique.

Opting for this technique should be judicious in an unstable patient.

hypothermia and coagulopathy. This is a very resource-intensive decision.

wall infections, anastomotic leak, entero-cutaneous fistula and mortality.

achieved by using various materials (Table 5):

incidence of ventral hernia development.

Use of a simple running technique

 Taking wide tissue bites (≥1 cm) Use of a short stitch interval (≤1 cm)

**Closed abdomen technique** 

**Open abdomen technique** 


Table 5. Temporary closure materials.

3. Non absorbable mesh like GORE-TEX and polypropylene can be used for closure with or without zipper. These materials have good tensile strength and provide additional option of repeated surgeries. The disadvantage, however, is mesh erosion into the bowel wall forming fistula and subsequent high risk of mesh infection.

4. Vacuum assisted closure device has the advantage of controlled drainage of secretions. It can also be left in situ for more than 48 hours which is adequate time for the patient to recover from systemic conditions like coagulopathy or metabolic acidosis (Damage control surgery). Increased cost is a major limiting factor against widespread use.

Image 4. Open abdomen technique (mesh)

### **6. Emerging new techniques for management of open abdomen**

### **6.1 Abdominal vacuum-assisted closure (V.A.C.) systems(10,11)**

The V.A.C.® Abdominal Dressing System is a specialty dressing indicated for temporary bridging of the open abdomen where primary closure is not possible and/or repeat abdominal entries are necessary.

The V.A.C. Abdominal Dressing System can be used to assist in the management of an open abdomen due to Abdominal Compartment Syndrome, trauma requiring damage control or staged abdominal repair, and other complex abdominal pathologies.

V.A.C systems are intended to create an environment that promotes wound healing by secondary or delayed primary intention by preparing the wound for closure, reducing edema, promoting granulation tissue formation and perfusion and by removing exudative and infectious material.

These systems are indicated for patients with open abdomen and dehisced wounds, partialthickness burns, chromic ulcers (such as diabetic, pressure or venous insufficiency).

The V.A.C. GranuFoam™ Silver Dressing is an effective barrier to bacterial penetration and may help reduce infection in the above wound types.

Placement of V.A.C systems directly in contact with exposed blood vessels, anastomotic sites, organs, or nerves is contraindicated. V.A.C. Therapy is also contraindicated for patients with malignancy in the wound, untreated osteomyelitis, non-enteric and unexplored fistulas and necrotic tissue with eschar present.

However, after debridement of necrotic tissue and complete removal of eschar, V.A.C. Therapy may be used.

4. Vacuum assisted closure device has the advantage of controlled drainage of secretions. It can also be left in situ for more than 48 hours which is adequate time for the patient to recover from systemic conditions like coagulopathy or metabolic acidosis (Damage control surgery). Increased cost is a major limiting factor against widespread use.

Image 4. Open abdomen technique (mesh)

abdominal entries are necessary.

and infectious material.

Therapy may be used.

**6. Emerging new techniques for management of open abdomen** 

The V.A.C.® Abdominal Dressing System is a specialty dressing indicated for temporary bridging of the open abdomen where primary closure is not possible and/or repeat

The V.A.C. Abdominal Dressing System can be used to assist in the management of an open abdomen due to Abdominal Compartment Syndrome, trauma requiring damage control or

V.A.C systems are intended to create an environment that promotes wound healing by secondary or delayed primary intention by preparing the wound for closure, reducing edema, promoting granulation tissue formation and perfusion and by removing exudative

These systems are indicated for patients with open abdomen and dehisced wounds, partial-

The V.A.C. GranuFoam™ Silver Dressing is an effective barrier to bacterial penetration and

Placement of V.A.C systems directly in contact with exposed blood vessels, anastomotic sites, organs, or nerves is contraindicated. V.A.C. Therapy is also contraindicated for patients with malignancy in the wound, untreated osteomyelitis, non-enteric and

However, after debridement of necrotic tissue and complete removal of eschar, V.A.C.

thickness burns, chromic ulcers (such as diabetic, pressure or venous insufficiency).

**6.1 Abdominal vacuum-assisted closure (V.A.C.) systems(10,11)**

staged abdominal repair, and other complex abdominal pathologies.

may help reduce infection in the above wound types.

unexplored fistulas and necrotic tissue with eschar present.

Following initiation of V.A.C Therapy, the wound can be re evaluated after 72 hours. This can either be done at the bed-side under sedation or under anaesthesia in the theatre. If the wound continues to be infected or dirty, the V.A.C system is reapplied. On the other hand, if the wound is clean, then the decision to proceed to secondary closure of the abdomen can be made.

(a) (b)

Image 5. a,b: V.A.C Therapy for open abdomen

### **6.2 Mist therapy (12)**

MIST Therapy® is a painless, noncontact, low frequency ultrasound delivered through a saline mist to the wound bed.These gentle sound waves stimulate the cells within and below the wound bed to promote healing.

The result of these gentle sound waves pushing against the tissue include:


### **7. Summary**

Surgical site infection (SSI) is a well known and commonly encountered scenario following major colorectal resection and has been documented as being a potentially morbid and costly complication.

Risk factors for surgical site infection include: smoking, diabetes, malnutrition, cancer, obesity, immunosuppression, cardiovascular disease and prior incision or irradiation at the surgical site. Meticulous surgical technique that avoids excessive tissue injury and ischemia while providing adequate hemostasis are important for preventing infection.

Surgeons can modify rates of infection with preventive measures that include antibiotic prophylaxis, proper skin preparation and maintenance of sterile conditions intra operatively. Proper surgical technique with gentle tissue handling and a secure closure that does not cause tissue ischemia are also important.

Infected wounds are opened, explored, drained, irrigated, débrided and dressed open. If fascial disruption is suspected, drainage should be performed in the operating room. The severity of the infection determines the need for antibiotic therapy. Once the infection has cleared and granulation tissue is apparent, the wound can be closed secondarily.

Fascial disruption is due to abdominal wall tension overcoming tissue or suture strength, or knot security. It can occur early or late in the postoperative period. With early fascial dehiscence, the skin closure may be intact depending upon the method of closure (ie, staples, sutures); the patient, nevertheless, is at risk for evisceration. Early postoperative fascial dehiscence is a surgical emergency. The late complication of fascial disruption is incisional hernia which can lead to bowel obstruction, ischemia and even death.

Management of the deep incisional surgical site and organ/space surgical site infection includes open abdomen technique using various types of dressings and mesh. Occasionally, single stage closure of the abdomen is used.

Of late, V.A.C dressings are the preferred choice for open abdomen management. However, the most recent development is the MIST therapy using low frequency ultrasound.

### **8. References**


Infected wounds are opened, explored, drained, irrigated, débrided and dressed open. If fascial disruption is suspected, drainage should be performed in the operating room. The severity of the infection determines the need for antibiotic therapy. Once the infection has

Fascial disruption is due to abdominal wall tension overcoming tissue or suture strength, or knot security. It can occur early or late in the postoperative period. With early fascial dehiscence, the skin closure may be intact depending upon the method of closure (ie, staples, sutures); the patient, nevertheless, is at risk for evisceration. Early postoperative fascial dehiscence is a surgical emergency. The late complication of fascial disruption is

Management of the deep incisional surgical site and organ/space surgical site infection includes open abdomen technique using various types of dressings and mesh. Occasionally,

Of late, V.A.C dressings are the preferred choice for open abdomen management. However,

[1] Robert L. Smith, MD, Jamie K. Bohl, MD, Shannon T. McElearney, MD, Charles M. Friel,

[2] Coppa GF, Eng K, Gouge TH, et al. Parenteral and oral antibiotics in elective colon and rectal surgery. A prospective, randomized trial. *Am J Surg*. 1983;145:62– 65. [3] Tang R, Chen HH, Wang YL, et al. Risk factors for surgical site infection after elective

[4] SHEA, APIC, CDC, SIS. Consensus paper on the surveillance of surgical wound

[5] Cruse PJ. Surgical wound infection. *In: Infectious Diseases*, Wonsiewicz MJ (Ed), WB

[6] Mangram AJ, Horan TC, Pearson ML, etal. Guideline for prevention of surgical site infection. *In: Infection Control and Hospital Epidemiology*, CDC 1999; 20:24 [7] Adapted from the Centers for Disease Control Guidelines for Prevention of Surgical Site

[8] Ceydeli A, Rucinski J, Wise L. Finding the best abdominal closure: an evidence-based

[9] Finding the best abdominal closure: an evidence-based review of the literature.AU

[10] Vacuum-Assisted Closure of Postoperative Abdominal Wounds: A Prospective Study.

Sriram Subramonia, Sarah Pankhurst, Brian J. Rowlands and Dileep N. Lobo, *World Journal of Surgery*, Volume 33, Number 5, 931-937, DOI: 10.1007/s00268-009-9947-z.

Infection (www.cdc.gov/ncidod/dhqp/gl\_surgicalsite.html).

Ceydeli A, Rucinski J, Wise LSO, Curr Surg. 2005;62(2):220.

[12] Howell M. Case study 000090-000307-000928 www.celleration.com

[11] Alvarez AA, Maxwell GL, Rodriguez GC, *Gynecol Oncol.* 2001Mar;80(3):413-6.

MD, Margaret M. Barclay, RN, ACNP-C, Robert G. Sawyer, MD, and Eugene F. Foley, MD :Wound Infection After Elective Colorectal Resection. *Annals of Surgery*

resection of the colon and rectum: a single-center prospective study of 2,809

cleared and granulation tissue is apparent, the wound can be closed secondarily.

incisional hernia which can lead to bowel obstruction, ischemia and even death.

the most recent development is the MIST therapy using low frequency ultrasound.

consecutive patients. *Annals of Surgery* 2001;234:181–9.

infections. *Infect Control Hosp Epidemiol* 1992; 13:599.

Saunders Co, Philadelphia 1992. p.7583:599.

review of the literature. *Curr Surg* 2005; 62:220

single stage closure of the abdomen is used.

v.239(5);May 2004.

**8. References** 

### *Edited by Yik-Hong Ho*

In recent years, significant progress in colorectal surgery has been made which includes laparoscopic techniques, pre-operative management, emergency colorectal surgery, fast track multimodal recovery, management of complex wound problems and colorectal cancer follow-up. "Contemporary Issues in Colorectal Surgical Practice" aims to bridge the gap between the journal article and the traditional textbook in these areas.

Contemporary Issues in Colorectal Surgical Practice

Contemporary Issues in

Colorectal Surgical Practice

*Edited by Yik-Hong Ho*

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