4.1 Uncomplicated PUD

Risk factors for the development of PUD should be evaluated. Patients should be advised to avoid NSAID intake, stop smoking, and limit drinking of alcohol. If the patient is H. pylori positive, it should be treated, and eradication of infection should be confirmed ≥4 weeks after completion of therapy [37]. There are different


first-line treatment in patients without history of exposure to macrolide and living in an area where H. pylori clarithromycin resistance is low. If the first-line therapy fails, susceptibility testing should be done if available, and susceptibility-based therapy should be given. If susceptibility testing is not available, salvage therapy should not contain the antibiotics used before. For example, if bismuth quadruple therapy fails, clarithromycin- or levofloxacin-based therapy should be used as salvage therapy. If clarithromycin-based therapy fails, bismuth quadruple therapy or levofloxacin-based therapy should be used as salvage therapy. First-line therapy generally fails in 25% of cases as a result of non-compliance, antibiotic resistance,

Acid suppressant therapy and mucosal cytoprotective agents are the main modes of therapy for the healing of PU. Acid suppressant therapy includes H2RAs and PPIs

Duration of H2RA therapy: 90% of duodenal ulcers are healed by H2RA in 6–8 weeks, whereas 90% of gastric ulcers are healed by H2RA in 12 weeks [48]. Duration of PPI therapy: in the case of H. pylori-associated peptic ulcers, 90% of the ulcers are healed by a 2-week course of PPI plus antibiotics for eradication of H. pylori infection. This regimen followed by additional 2 weeks of PPI does not make much difference in healing of peptic ulcer. PPI therapy should be

Cimetidine 800 mg qhs 4–8 weeks Gynecomastia, impotence, polymyositis, interstitial

Ranitidine 150 mg BID 4–8 weeks Diarrhea, constipation, xerostomia, xeroderma

Famotidine 40 mg qhs 4–8 weeks Agranulocytosis, angioedema, anaphylaxis, seizure Nizatidine 300 mg qhs 4–8 weeks Nausea, vomiting, dyspepsia, insomnia, somnolence,

Esomeprazole 20–40 mg qd 4–8 weeks Chronic: hypocalcemia, hypomagnesemia, iron

nephritis, confusion, agitation, vitamin B12 deficiency

Vitamin B12 deficiency

vitamin B12 deficiency

deficiency, vitamin B12 deficiency, Clostridium difficile infection, pneumonia, acute interstitial nephritis, risk of fracture, drug-induced lupus erythematosus [47]

prior exposure to antibiotic, smoking, and younger age [44–46].

H2RA Dose Side effects

PPI Dose Side effects Omeprazole 20–40 mg qd 4–8 weeks Acute: headache, diarrhea

which are listed in Tables 2 and 3.

DOI: http://dx.doi.org/10.5772/intechopen.86652

Peptic Ulcer Disease

qhs, every night at bed time.

H2RA with dose and side effects.

Lansoprazole 15–30 mg qd 4–8 weeks Dexlansoprazole 30–60 mg qd 4–8 weeks Pantoprazole 20–40 mg qd 4–8 weeks Rabeprazole 20 mg qd 4–8 weeks

Table 2.

qd, daily.

Table 3.

9

PPI with dose and side effects.

#### Table 1.

Treatment of H. pylori infection.

regimens of anti-H. pylori therapy available. Patients' previous history of antibiotic exposure and prevalence of regional antibiotic resistance should be taken into consideration. Treatment of H. pylori infection is summarized in Table 1 [41]. Antibiotics, histamine 2 receptor antagonists (H2RA), PPI, sucralfate, and bismuthcontaining medications (Pepto-Bismol) can interfere with the results of urea breath test and stool for H. pylori antigen test and may give a false-negative result. Patients should stop taking these medications at least 2 weeks prior to these tests [42, 43]. But patients can continue taking antacids (except Maalox total relief) as they do not affect the accuracy of the tests.

Bismuth quadruple therapy or concomitant therapy can be considered as the first-line therapy against H. pylori infection. PAC therapy should be considered as first-line treatment in patients without history of exposure to macrolide and living in an area where H. pylori clarithromycin resistance is low. If the first-line therapy fails, susceptibility testing should be done if available, and susceptibility-based therapy should be given. If susceptibility testing is not available, salvage therapy should not contain the antibiotics used before. For example, if bismuth quadruple therapy fails, clarithromycin- or levofloxacin-based therapy should be used as salvage therapy. If clarithromycin-based therapy fails, bismuth quadruple therapy or levofloxacin-based therapy should be used as salvage therapy. First-line therapy generally fails in 25% of cases as a result of non-compliance, antibiotic resistance, prior exposure to antibiotic, smoking, and younger age [44–46].

Acid suppressant therapy and mucosal cytoprotective agents are the main modes of therapy for the healing of PU. Acid suppressant therapy includes H2RAs and PPIs which are listed in Tables 2 and 3.

Duration of H2RA therapy: 90% of duodenal ulcers are healed by H2RA in 6–8 weeks, whereas 90% of gastric ulcers are healed by H2RA in 12 weeks [48].

Duration of PPI therapy: in the case of H. pylori-associated peptic ulcers, 90% of the ulcers are healed by a 2-week course of PPI plus antibiotics for eradication of H. pylori infection. This regimen followed by additional 2 weeks of PPI does not make much difference in healing of peptic ulcer. PPI therapy should be


Table 2. H2RA with dose and side effects.


Table 3. PPI with dose and side effects.

regimens of anti-H. pylori therapy available. Patients' previous history of antibiotic exposure and prevalence of regional antibiotic resistance should be taken into consideration. Treatment of H. pylori infection is summarized in Table 1 [41]. Antibiotics, histamine 2 receptor antagonists (H2RA), PPI, sucralfate, and bismuthcontaining medications (Pepto-Bismol) can interfere with the results of urea breath test and stool for H. pylori antigen test and may give a false-negative result. Patients should stop taking these medications at least 2 weeks prior to these tests [42, 43]. But patients can continue taking antacids (except Maalox total relief) as they do not

Regimen Drugs Duration Eradication rate

PAC therapy PPI standard dose BID plus amoxicillin 1 g BID plus

PAM therapy PPI standard dose BID plus amoxicillin 1 g BID plus

Bismuth quadruple therapy

Digestive System - Recent Advances

Concomitant therapy

Sequential therapy

Hybrid therapy

Levofloxacin triple therapy

Levofloxacin sequential therapy

Novel concomitant therapy

Table 1.

8

clarithromycin 500 mg BID

metronidazole 500 mg TID

PPI standard dose BID plus bismuth subcitrate (120– 300 mg) or subsalicylate (300 mg) QID plus tetracycline 500 mg QID plus metronidazole 250 MG QID

PPI standard dose BID plus amoxicillin 1 g BID plus clarithromycin 500 mg BID plus metronidazole or tinidazole 500 mg BID

PPI standard dose plus amoxicillin 1 g BID for 5 days followed by PPI plus clarithromycin 500 mg plus either metronidazole or tinidazole 500 mg BID for additional 5 days

PPI standard dose plus amoxicillin 1 g BID for 7 days followed by PPI standard dose plus amoxicillin 1 g plus clarithromycin 500 mg plus metronidazole 500 mg BID for additional 7 days

PPI standard dose and amoxicillin 1 g BID plus levofloxacin 500 mg QD

PPI standard dose plus amoxicillin 1 g BID for 5– 7 days followed by PPI standard dose plus amoxicillin 1 g plus metronidazole 500 mg BID and levofloxacin 500 mg QD for additional 5–7 days

doxycycline 100 mg QD and nitazoxanide 500 mg BID

PPI standard dose and amoxicillin 1 g TID (if allergic to penicillin, bismuth subcitrate 240 mg QID) plus rifabutin 150 mg and ciprofloxacin 500 mg BID

LOAD therapy PPI (double dose) plus levofloxacin 250 mg plus

BID, twice a day; QID, four times a day; QD, once a day.

(%)

84.4

93.4

92.2

amoxicillin 95.2 Regimen with bismuth subcitrate 94.2

14 days 70–85

14 days 70–85

10–14 days 75–90

10–14 days 94.4

10–14 days 83.1

7–10 days 88.9

10 days Regimen with

Total 10 days

Total 14 days

Total 10–14 days

Bismuth quadruple therapy or concomitant therapy can be considered as the first-line therapy against H. pylori infection. PAC therapy should be considered as

affect the accuracy of the tests.

Treatment of H. pylori infection.

continued for 8 weeks in case of gastric ulcer and 4 weeks in case of duodenal ulcer [49].

dysplasia, or adenoma; and patient has risk factors for gastric cancer which include H. pylori positivity, age > 50 years, family history of gastric cancer, and coming from a high prevalent area of gastric cancer (South Korea, Mongolia, Japan, China, Bhutan, Kyrgyzstan, Chile, etc.). If the gastric ulcer seems to be active or healing on surveillance endoscopy, four-quadrant biopsies from the

2. Surveillance endoscopy may not be necessary if the patient does not have any risk factor for malignancy and the gastric ulcer is small, benign appearing, and antral in location due to NSAID and the initial biopsy does not show any

In case of duodenal ulcer, surveillance endoscopy is generally not required because of low risk of malignancy. But if the patient remains symptomatic or symptoms recur despite medical therapy, surveillance endoscopy should be considered to evaluate for refractory ulcer or non-peptic nature of the ulcer which

When the ulcer does not heal up after a 12-week course of PPI therapy, it is called refractory ulcer. 5–10% ulcers are refractory ulcers. When the ulcer recurs after complete healing of the ulcer, it is called recurrent ulcer. 5–30% ulcers are recurrent ulcers. The two most important causes of refractory and recurrent ulcers are continued NSAID use and persistent H. pylori infection [57]. Other important factors include cigarette smoking, smoking of crack cocaine, concurrent use of corticosteroid, cytotoxic drugs (sirolimus, mycophenolate mofetil), alendronate, methamphetamine, idiopathic hypersecretory duodenal ulcer, antral G-cell hyperplasia, gastrinoma, Crohn's disease, sarcoidosis, cancer, non-H. pylori infection (Helicobacter heilmannii), and infiltrative condition like gastrointestinal stromal

Patients with refractory or recurrent ulcers should be thoroughly investigated to find out the causative factors which should be addressed. Twice daily PPI therapy should be given for another 12 weeks. Then upper endoscopy should be done to document complete healing of the ulcer. Patients with gastric ulcer should be

Common complications of PUD include bleeding, perforation, penetration, and

About 50% of all cases of upper gastrointestinal bleeding are caused by PUD [58]. Patients may present with hematemesis, melena, anemia, or heme-positive stool. At presentation, the patient's hemodynamic status (pulse, blood pressure) should be checked and resuscitative measures should be started. Patients should be given intravenous crystalloid fluid to maintain blood pressure, and parenteral PPI (esomeprazole or pantoprazole) should be started (continuous infusion or twice daily intravenously). PPI therapy increases intragastric pH with stabilization of

edges and base of the ulcer should be taken [55].

includes Crohn's disease, lymphoma, or tuberculosis.

referred for surgery if ulcer does not heal by 24 weeks.

dysplasia or malignancy [56].

DOI: http://dx.doi.org/10.5772/intechopen.86652

Peptic Ulcer Disease

7. Refractory and recurrent ulcers

tumor and Kaposi sarcoma.

8. Complications

8.1 Bleeding

11

gastric outlet obstruction.

In the case of NSAID-induced PUD, NSAIDs should be withdrawn if possible, but PPIs are the drugs of choice. PPIs should be continued for at least 8 weeks for the healing of PU. But maintenance dose of PPI should be continued to prevent ulcer complications if the patient needs to be on NSAID or aspirin for other medical conditions.

#### 5. Mucosal cytoprotective agents

Misoprostol and sucralfate are mucosal cytoprotective agents.

Misoprostol is a synthetic analogue of prostaglandin E which is trophic to gastroduodenal mucosa, stimulates mucus and bicarbonate secretion from the gastroduodenal mucosa, and can form hydrophobic surfactant-like phospholipids in the gastric epithelial cells [50]. Misoprostol can also inhibit gastric acid secretion by suppressing histamine-stimulated cyclic AMP production but does not induce hypergastrinemia [51]. Misoprostol can heal both gastric and duodenal ulcers. Misoprostol 200 microgram four times a day should be given for 12 weeks. It can prevent mucosal damage and formation of ulcers from the deleterious effects of low-dose aspirin, NSAIDs, smoking, and alcohol [52]. Misoprostol is approved in the United States for the prevention of NSAID-induced PUD. As misoprostol can accelerate intestinal transit time and increase intestinal water and electrolyte secretion, abdominal cramps and mild to moderate diarrhea can happen in up to 30% of cases. Diarrhea can be reduced by taking food with misoprostol. Misoprostol can also cause nausea, vomiting, menstrual cramps, and vaginal bleeding (due to uterine contraction). Misoprostol is contraindicated in pregnant patients.

Sucralfate is the aluminum salt of sulfated sucrose. It coats the gastroduodenal mucosa (both ulcerated and non-ulcerated areas); binds acid and pepsin; stimulates the secretion of bicarbonate, prostaglandin, and epidermal growth factor; and thus helps in healing of PU. Sucralfate is as good as H2RA in healing PU (duodenal ulcer 60–90% at 4–6 weeks and gastric ulcer 90% at 12 weeks) and has a lower rate of recurrence of duodenal ulcer after healing as compared to H2RA [53, 54]. In the United States, sucralfate is approved for the treatment of active duodenal ulcer not related to NSAID. Side effects of sucralfate include nausea, vomiting, gastric upset, itching, and skin rash. Less than 5% of sucralfate is absorbed from the gastrointestinal tract into the systemic circulation and eliminated primarily in the urine. Sucralfate should be avoided in patients with chronic kidney disease as it contains aluminum.

#### 6. Role of follow-up endoscopy

In the case of gastric ulcer, follow-up endoscopy is recommended 12 weeks after medical therapy to evaluate for underlying malignancy. Surveillance endoscopy should be individualized:

1. Surveillance endoscopy is necessary in patients with giant ulcer (>2 cm) and malignant-looking ulcer (thick mucosal folds, irregular ulcer edges, mass lesion) on index endoscopy; ulcer biopsy was not done on initial endoscopy; initial endoscopy was done for upper gastrointestinal bleeding and unknown etiology of the ulcer; patient remains symptomatic even after taking medical therapy; index endoscopy showed gastric atrophy, intestinal metaplasia,

continued for 8 weeks in case of gastric ulcer and 4 weeks in case of duodenal

Misoprostol and sucralfate are mucosal cytoprotective agents.

ine contraction). Misoprostol is contraindicated in pregnant patients.

In the case of NSAID-induced PUD, NSAIDs should be withdrawn if possible, but PPIs are the drugs of choice. PPIs should be continued for at least 8 weeks for the healing of PU. But maintenance dose of PPI should be continued to prevent ulcer complications if the patient needs to be on NSAID or aspirin for other medical

Misoprostol is a synthetic analogue of prostaglandin E which is trophic to gastroduodenal mucosa, stimulates mucus and bicarbonate secretion from the gastroduodenal mucosa, and can form hydrophobic surfactant-like phospholipids in the gastric epithelial cells [50]. Misoprostol can also inhibit gastric acid secretion by suppressing histamine-stimulated cyclic AMP production but does not induce hypergastrinemia [51]. Misoprostol can heal both gastric and duodenal ulcers. Misoprostol 200 microgram four times a day should be given for 12 weeks. It can prevent mucosal damage and formation of ulcers from the deleterious effects of low-dose aspirin, NSAIDs, smoking, and alcohol [52]. Misoprostol is approved in the United States for the prevention of NSAID-induced PUD. As misoprostol can accelerate intestinal transit time and increase intestinal water and electrolyte secretion, abdominal cramps and mild to moderate diarrhea can happen in up to 30% of cases. Diarrhea can be reduced by taking food with misoprostol. Misoprostol can also cause nausea, vomiting, menstrual cramps, and vaginal bleeding (due to uter-

Sucralfate is the aluminum salt of sulfated sucrose. It coats the gastroduodenal mucosa (both ulcerated and non-ulcerated areas); binds acid and pepsin; stimulates the secretion of bicarbonate, prostaglandin, and epidermal growth factor; and thus helps in healing of PU. Sucralfate is as good as H2RA in healing PU (duodenal ulcer 60–90% at 4–6 weeks and gastric ulcer 90% at 12 weeks) and has a lower rate of recurrence of duodenal ulcer after healing as compared to H2RA [53, 54]. In the United States, sucralfate is approved for the treatment of active duodenal ulcer not related to NSAID. Side effects of sucralfate include nausea, vomiting, gastric upset, itching, and skin rash. Less than 5% of sucralfate is absorbed from the gastrointestinal tract into the systemic circulation and eliminated primarily in the urine. Sucralfate should be avoided in patients with chronic kidney disease as it contains

In the case of gastric ulcer, follow-up endoscopy is recommended 12 weeks after medical therapy to evaluate for underlying malignancy. Surveillance endoscopy

1. Surveillance endoscopy is necessary in patients with giant ulcer (>2 cm) and malignant-looking ulcer (thick mucosal folds, irregular ulcer edges, mass lesion) on index endoscopy; ulcer biopsy was not done on initial endoscopy; initial endoscopy was done for upper gastrointestinal bleeding and unknown etiology of the ulcer; patient remains symptomatic even after taking medical therapy; index endoscopy showed gastric atrophy, intestinal metaplasia,

ulcer [49].

conditions.

aluminum.

10

6. Role of follow-up endoscopy

should be individualized:

5. Mucosal cytoprotective agents

Digestive System - Recent Advances

dysplasia, or adenoma; and patient has risk factors for gastric cancer which include H. pylori positivity, age > 50 years, family history of gastric cancer, and coming from a high prevalent area of gastric cancer (South Korea, Mongolia, Japan, China, Bhutan, Kyrgyzstan, Chile, etc.). If the gastric ulcer seems to be active or healing on surveillance endoscopy, four-quadrant biopsies from the edges and base of the ulcer should be taken [55].

2. Surveillance endoscopy may not be necessary if the patient does not have any risk factor for malignancy and the gastric ulcer is small, benign appearing, and antral in location due to NSAID and the initial biopsy does not show any dysplasia or malignancy [56].

In case of duodenal ulcer, surveillance endoscopy is generally not required because of low risk of malignancy. But if the patient remains symptomatic or symptoms recur despite medical therapy, surveillance endoscopy should be considered to evaluate for refractory ulcer or non-peptic nature of the ulcer which includes Crohn's disease, lymphoma, or tuberculosis.

### 7. Refractory and recurrent ulcers

When the ulcer does not heal up after a 12-week course of PPI therapy, it is called refractory ulcer. 5–10% ulcers are refractory ulcers. When the ulcer recurs after complete healing of the ulcer, it is called recurrent ulcer. 5–30% ulcers are recurrent ulcers. The two most important causes of refractory and recurrent ulcers are continued NSAID use and persistent H. pylori infection [57]. Other important factors include cigarette smoking, smoking of crack cocaine, concurrent use of corticosteroid, cytotoxic drugs (sirolimus, mycophenolate mofetil), alendronate, methamphetamine, idiopathic hypersecretory duodenal ulcer, antral G-cell hyperplasia, gastrinoma, Crohn's disease, sarcoidosis, cancer, non-H. pylori infection (Helicobacter heilmannii), and infiltrative condition like gastrointestinal stromal tumor and Kaposi sarcoma.

Patients with refractory or recurrent ulcers should be thoroughly investigated to find out the causative factors which should be addressed. Twice daily PPI therapy should be given for another 12 weeks. Then upper endoscopy should be done to document complete healing of the ulcer. Patients with gastric ulcer should be referred for surgery if ulcer does not heal by 24 weeks.

### 8. Complications

Common complications of PUD include bleeding, perforation, penetration, and gastric outlet obstruction.

#### 8.1 Bleeding

About 50% of all cases of upper gastrointestinal bleeding are caused by PUD [58]. Patients may present with hematemesis, melena, anemia, or heme-positive stool. At presentation, the patient's hemodynamic status (pulse, blood pressure) should be checked and resuscitative measures should be started. Patients should be given intravenous crystalloid fluid to maintain blood pressure, and parenteral PPI (esomeprazole or pantoprazole) should be started (continuous infusion or twice daily intravenously). PPI therapy increases intragastric pH with stabilization of

blood clot and reduces the risk of rebleeding and the need for surgery but does not decrease overall mortality [59]. Blood transfusion should be given to keep the hemoglobin ≥7 gm/dl, but in patients with hypovolemia or comorbidities like coronary artery disease, hemoglobin target should be higher. Risk assessment should be done to categorize high-risk or low-risk patients, level of care, need for blood transfusion, timing of endoscopy, and timing of discharge. The Glasgow-Blatchford bleeding score (GBS) is a useful screening tool (Table 4) to determine the need for intervention [60]. Patients with a score of 0 are considered as low risk with minimum risk of needing interventions like blood transfusion, endoscopy, and surgery, and they should be considered for early discharge from the hospital. But all other values (>0) fall into the category of high risk in terms of need for blood transfusion, endoscopy, and surgery. A score of 6 or more has >50% risk of needing intervention.

After resuscitation and stabilization, EGD should be done for diagnostic and therapeutic purposes. During endoscopy, Forrest classification should be used to assess the need for endoscopic intervention [61]. The different Forrest classes with their prevalence and risk of rebleeding are mentioned in Table 5 [62]. Patients with Forrest classes Ia, Ib, IIa, and IIb are considered to be high-risk candidates, and endoscopic treatment should be provided to reduce the risk of rebleeding. Patients with Forrest classes IIc and III do not require any endoscopic intervention. In fact,

patients with Forrest class III can resume a regular diet and can be discharged home as long as they are hemodynamically stable, with stable hemoglobin and without other comorbidities, and they have somebody at home to watch them [63]. Endoscopic treatment options can categorized into three main types:

Endoscopic finding Prevalence

Ia Spurting arterial bleed 10 90

IIa Non-bleeding visible vessel 25 50 IIb Adherent blood clot 10 25–30 IIc Flat pigmented spot 10 7–10 III Clean-based ulcer 35 3–5

Ib Oozing of blood without visible

DOI: http://dx.doi.org/10.5772/intechopen.86652

Forrest classes with prevalence and risk of recurrent bleeding.

vessel

(%)

Risk of recurrent bleeding on medical management (%)

10 10–20

1. Injection therapy: it is the oldest endoscopic hemostatic method. Epinephrine (1:10,000 dilution) 0.2–2 ml aliquots are injected in four quadrants of the bleeding stigmata. Initial hemostasis is obtained by its tamponade effect as well as vasoconstrictive effect. But as it is less effective as a monotherapy, other modalities of endoscopic treatment are added for better hemostasis [64].

2.Thermal therapy: it includes contact methods by bipolar or monopolar cauterization and noncontact method by argon plasma coagulation (APC). Contact methods work by coaptive coagulation. Bipolar cauterization is most commonly used nowadays. A combination of epinephrine injection and bipolar

cauterization is more effective than either modality alone in achieving hemostasis [65]. The APC machine has a high-frequency monopolar

generally healed up in 2–3 weeks.

Forrest class

Peptic Ulcer Disease

Table 5.

13

electrosurgical generator, argon gas chamber, gas flowmeter, grounding pad, flexible APC delivery catheter, and foot switch to activate gas and energy. Argon gas release with delivery of electric current is synchronized by the foot switch. The APC probe should be within 2–8 mm from the site of the targeted tissue to induce plasma coagulation. The depth of the burn can be preset between 0.5 and 3 mm. APC is an effective method of hemostasis in bleeding peptic ulcer [66]. But APC can cause superficial ulcerations which are

3.Mechanical therapy: endoclips are widely used to stop bleeding from peptic ulcer. There are different clips available which include resolution clip,

endoscopic hemoclip, Quick Clip2 (rotatable clip), Duraclip, and SureClip. All these clips can go through the standard 2.8 mm endoscope channel and can stop bleeding by grasping the bleeding vessel, reducing the chance of

rebleeding and need for surgery. Endoclips have been found to be superior to injection therapy but comparable to thermocoagulation in bleeding PU [67]. They do not cause any tissue trauma, and as a result, ulcer healing is not impaired. They are also MRI compatible. Disadvantages of endoclipping include the following: (a) sometimes technical difficulty to clip the lesions in locations like the posterior duodenal bulb, posterior gastric body, and proximal lesser curve of the stomach, (b) limitation of use in large blood vessel (>2 mm


Table 4. GBS.


Table 5.

blood clot and reduces the risk of rebleeding and the need for surgery but does not decrease overall mortality [59]. Blood transfusion should be given to keep the hemoglobin ≥7 gm/dl, but in patients with hypovolemia or comorbidities like coronary artery disease, hemoglobin target should be higher. Risk assessment should be done to categorize high-risk or low-risk patients, level of care, need for blood transfusion, timing of endoscopy, and timing of discharge. The Glasgow-Blatchford bleeding score (GBS) is a useful screening tool (Table 4) to determine the need for intervention [60]. Patients with a score of 0 are considered as low risk with minimum risk of needing interventions like blood transfusion, endoscopy, and surgery, and they should be considered for early discharge from the hospital. But all other values (>0) fall into the category of high risk in terms of need for blood transfusion, endoscopy, and surgery. A score of 6 or more has >50% risk of needing interven-

After resuscitation and stabilization, EGD should be done for diagnostic and therapeutic purposes. During endoscopy, Forrest classification should be used to assess the need for endoscopic intervention [61]. The different Forrest classes with their prevalence and risk of rebleeding are mentioned in Table 5 [62]. Patients with Forrest classes Ia, Ib, IIa, and IIb are considered to be high-risk candidates, and endoscopic treatment should be provided to reduce the risk of rebleeding. Patients with Forrest classes IIc and III do not require any endoscopic intervention. In fact,

Admission risk marker Score component value

6.5–8.0 2 8.0–10.0 3 10.0–25 4 >25 6

12.0–12.9 1 10.0–11.9 3 <10.0 6

10.0–11.9 1 <10.0 6

100–109 1 90–99 2 <90 3

Pulse ≥100 (per min) 1 Presentation with melena 1 Presentation with syncope 2 Hepatic disease 2 Cardiac failure 2

tion.

Blood urea (mmol/L)

Digestive System - Recent Advances

Hemoglobin (g/dL) for men

Hemoglobin (g/dL) for women

Systolic blood pressure (mm Hg)

Other markers

Table 4. GBS.

12

Forrest classes with prevalence and risk of recurrent bleeding.

patients with Forrest class III can resume a regular diet and can be discharged home as long as they are hemodynamically stable, with stable hemoglobin and without other comorbidities, and they have somebody at home to watch them [63].

Endoscopic treatment options can categorized into three main types:


in diameter), (c) difficulty to grasp fibrotic tissue, and (d) requirement of multiple clips [68].

12. Failure of endoscopic therapy

DOI: http://dx.doi.org/10.5772/intechopen.86652

14. Prognosis of bleeding peptic ulcer

morbidity and mortality if not treated early.

13. Role of surgery

Peptic Ulcer Disease

radiology.

about 10% [77].

15. Perforation

15

If the endoscopic therapy fails to achieve hemostasis, the next step will be angiography with transarterial embolization (TAE). Different agents are used for embolization, and these include Gelfoam, endocoils, cyanoacrylic glues, and polyvinyl alcohol. The success rate of TAE in obtaining hemostasis is 52–98%, but

Surgery is indicated if TAE fails to stop PU bleeding. Emergency surgery involves plication or oversewing of the ulcer with ligation of the bleeding artery and truncal vagotomy and pyloroplasty. Wong et al. compared surgery vs. TAE in bleeding PU patients who had failed endoscopic therapy. Surgery was associated with less recurrent bleeding but more complications when compared with TAE. There was no significant difference in the mean length of hospital stay, need for blood transfusion, and 30-day mortality between the two groups [76]. In practice, the surgical intervention continues to diminish, but the radiological intervention continues to increase in acute PU bleeding patients who have unsuccessful endoscopic therapy. Surgery is also recommended for (a)

patients with perforation, (b) shock due to recurrent bleeding, (c) patients with hemodynamic instability despite adequate resuscitative measures needing more than three units of blood transfusion, and (d) unavailability of interventional

The outcome depends on successful endoscopic hemostasis without recurrent bleeding. The risk factors for recurrent bleeding include patients with renal failure on dialysis; elderly patients on NSAID, antiplatelet agents, and anticoagulants; patients with ulcer located on the posterior duodenal wall and lesser curve of the stomach; and patients with active bleeding ulcer during endoscopy. Despite the tremendous advances in technology, the mortality of acute PU bleeding remains

In patients with PUD, the lifetime prevalence of perforation is 5%. Patients generally present with acute abdomen. The triad of sudden onset of abdominal pain, tachycardia, and abdominal rigidity is highly suggestive of PU perforation. Smoking, NSAIDs, corticosteroids, old age, H. pylori infection, stress, and previous history of PUD are risk factors for perforation [78]. Upright chest X-ray is generally diagnostic, but it can miss free air under the diaphragm in 15% of cases. CT (computerized tomography) is very sensitive in detecting the presence and site of perforation [79]. CT with oral contrast may also show leak. Exploratory laparotomy with omental patch is the treatment of choice. PU perforation carries increased risk of

recurrent bleeding can occur in 10–20%, requiring repeat TAE [75].

Another clip called Ovesco clip is an over-the-scope clip used to stop peptic ulcer bleeding. The bleeding area is suctioned into a cup attached to the scope, and then the clip is deployed like band ligation.

A combination of at least two modalities of endoscopic treatment (injection, thermal, or mechanical) is now the standard of care in the treatment of peptic ulcer bleeding.

#### 9. Endoscopic Doppler ultrasound

An ultrasound probe is passed through the endoscope channel and placed directly onto the area of bleeding. An audible sound is heard if there is blood flow. Arterial or venous blood flow can be detected. It is useful after endoscopic treatment to evaluate the presence of any residual blood flow which can increase the potential for rebleeding. It is also useful in Forrest IIc and III ulcers to find out any vascular signal. Doppler ultrasound-guided endoscopic hemostasis reduces 30-day rebleeding rate significantly and is also cost-effective [69].

Hemospray or hemostatic nanopowder is an alternative approach to obtain hemostasis. The powder is delivered through a catheter which passes through the endoscope channel, and the powder is then sprayed over the bleeding site. The powder forms a stable mechanical barrier at the site of bleeding. Initial success rate in obtaining hemostasis is 75–100%, but rebleeding rate is 10–49% [70]. So hemospray should be used as a bridge therapy in massive peptic ulcer bleeding when standard endoscopic treatment fails.

Endoscopic therapy can control acute peptic ulcer bleeding with high success. Primary hemostasis can be obtained in more than 90% of cases, but rebleeding can occur in up to 15% of cases after therapeutic endoscopic procedure [71].

#### 10. Role of second-look endoscopy

Second-look endoscopy is not routinely recommended after initial endoscopy for the management of PU bleeding unless the endoscopist is concerned that suboptimal treatment was given in the first endoscopy or there was poor visualization due to blood or food debris during the first endoscopy [72].

#### 11. Complications of endoscopic treatment

Complications could be due to sedation, patients' comorbidities, and endoscopy itself. Sedation-related complications include hypoventilation, hypoxia, aspiration pneumonia, airway obstruction, arrhythmia, pulmonary embolism, myocardial infarction, phlebitis, and vasovagal attack [73]. The complications of endoscopic hemostasis include exacerbation of bleeding and perforation, but the overall incidence is <0.5%. The rate of perforation after contact thermal therapy could be as high as 2%. Following thermal therapy, induction or exacerbation of bleeding can occur in up to 5% of cases [74].

## 12. Failure of endoscopic therapy

If the endoscopic therapy fails to achieve hemostasis, the next step will be angiography with transarterial embolization (TAE). Different agents are used for embolization, and these include Gelfoam, endocoils, cyanoacrylic glues, and polyvinyl alcohol. The success rate of TAE in obtaining hemostasis is 52–98%, but recurrent bleeding can occur in 10–20%, requiring repeat TAE [75].
