Peptic ulcer disease

 

PEPTIC ULCER DISEASE (PUD):

Peptic ulcer is the focal defect in gastric or duodenal mucosa extending into the submucosa or even deeper leading to bleeding and perforation.

Duodenal ulcers are 2-3 times more common than gastric ulcers. Duodenal ulcers are produced by overproduction of the acid while the gastric ulcer is usually produced by weakness in the defense of gastric mucosa.

Causes of peptic ulceration:

• 95% of duodenal ulcers are associated with H-Pylori infection while in 85% of gastric ulcers H-pylori is found positive.

• NSAIDS reduce prostaglandin production which are mucosal protective agents.

• Smoking, caffeine and spicy foods increase acid production.

• Ischemia.

• Stress

• Prolonged steroids intake

• Zollinger Ellison syndrome.

Duodenal ulcer:

• Duodenal ulcer usually occurs in the first part of duodenum.

• The ulcers in the anterior wall usually perforate leading to peritonitis while posteriorly placed ulcers erode the gastro duodenal artery leading to hemorrhage (Hematemesis). When the chronic ulcer heals it can lead to fibrosis and stricture of the duodenum leading to gastric outlet obstruction. 

• The chances of development of malignancy are negligible in duodenal ulcer so it is not necessary to get a biopsy of the ulcer while performing gastroduodenoscopy.

• The pain of duodenal ulcer is relieved by food intake and these patients are usually obese while gastric ulcer pain is aggravated by food intake and these patients are usually thin and slim. Pain of duodenal ulcer frequently occurs at night (2:00 AM to 4:00 AM)

Gastric ulcer:

• Gastric ulcers are usually large and involve the lesser curvature of the stomach. 

• They can erode into the pancreas, transverse colon and splenic artery. The chances of development of gastric carcinoma are high in gastric ulcers. Any gastric ulcer should be considered malignant until proved otherwise, so it is necessary that any ulcer encountered during gastroscopy should be biopsied. Multiple biopsies (upto 10) should be taken before labeling the gastric ulcer as benign.

Clinical features:

Epigastric pain:

The most common presenting complaint is burning epigastric pain. Two third of patients with duodenal ulcer will have pain that awaken them during sleep while gastric ulcer pain more commonly occur with eating and is less likely to

awaken the patient from sleep.

Periodicity:

The pain is usually periodic in nature. Symptoms may disappear for weeks and months to return

again.

Alteration in weight:

Patients with gastric ulcer are usually underweight while the patients of duodenal ulcer may be overweight.

Bleeding:

All peptic ulcers can bleed.

Investigations:

1. Gastroduodenoscopy:

Young patients with typical epigastric pain and dyspepsia can be treated empirically with PPIS for PUD without confirming the diagnosis.All patients above 45 years of age with suspicion of PUD should have upper GI endoscopy and all patients regardless of age should have endoscopy if any of the alarming symptoms (weight loss, recurrent vomiting, dysphagia, bleeding, and anemia) are present

Upper GI endoscopy is the gold standard investigation. The ulcer can be viewed and biopsied. All the stomach ulcers should be biopsied.

2. Detection of H pylori:

As we have already discussed, 90% of duodenal ulcers and more than 80% of gastric ulcers are associated with H-Pylori. Infection so tests should also be performed for

detection of H.pylori. These are given below.

• CLO test: Urease Test

Also called quick urease test (H.pylori is urease producing organism).In this test biopsy is taken from gastric or duodenal mucosa and the tissue is placed in a medium containing urea and pH sensitive indicator. If H.pylori is present in biopsied tissue, the urease enzyme will convert the urea into ammonia which in turn will change the pH of the medium.

• Carbon-13 labeled urea breath test:

This is quick to perform and is used for screening of H-Pylori. In this test, the patient ingests urea labeled with carbon-13. The labeled urea is acted upon by urease present in H.pylori and is converted into ammonia and carbon dioxide. In the subsequent 10-30 minutes, the detection of isotope-labeled carbon dioxide in the exhaled breath indicates urease.

• Stool test:

Detection of H.pylori antigen in the stool is 90% sensitive and 95% specific.

• Histology and culture:- Gold standard

Histological examination of antral mucosal biopsy using special stain is the gold standard test for H.pylori detection

3. Serum gastrin level:

A baseline serum gastrin level is appropriate to rule out gastrinoma.

How to treat peptic ulcer?

Medical treatment:

PPIS are the mainstay of medical treatment for PUD. Patients hospitalized for complications of ulcer should be given intravenous infusion of PPIS and lifelong PPIs therapy after discharge unless the definitive causative factor has been eliminated. These patients should be advised to stop smoking and alcohol intake. Patients requiring NSAIDS or aspirin for any condition should receive concomitant PPIs or H2 blockers. If H.pylori infection is documented it should be eradicated. Generally PPIs therapy can be / stopped three months after elimination of causative factors (NSAIDs, H.pylori) however long term therapy may be needed in patients with complicated peptic ulcer disease

Eradication therapy:

Eradication of H.pylori infection is routinely recommended to patients with peptic ulceration because of its high association with the disease.

There are various regimens for eradication of H.pylori; some of them are given below

• PPI twice daily + clarithromycin 500mg bid+ amoxicillin 1000mg bid for two weeks

• PPI + clarithromycin 500mg bid metronidazole bid for two weeks

• PPI + amoxicillin 1000mg bid for 5 days then PPI + clarithromycin 500mg + tinidazole 500mg bid for 5 days

Salvage regimens for patients who fail one of the above mentioned regimens

• Bismuth subsalicylate 525 mg bid + metronidazole 250mg qid + tetracycline 500mg qid + PPI for 10-14 days

• PPI + amoxicillin 1000mg bid + levofloxacin 500mg bid for 10 days

SURGICAL TREATMENT:

By the introduction of very effective antisecretory drugs (PPIS, H2RA). Surgery is rarely required for uncomplicated peptic ulcers. But it may be needed for complications of peptic ulcer like perforation, bleeding, fibrosis etc.

Surgery for Duodenal ulcer:

The main aim of duodenal ulcer surgery was to reduce the exposure of acid to the duodenum which in turn allows the ulcer to heal. Various procedures described below are of historical importance as these are rarely performed these days

i. Billroth I gastrectomy: (Gastroduodenostomy

Distal stomach (antrum) is mobilized and resected as it is considered as chief source of acid production and is anastomosed with duodenum. The resected specimen also includes the ulcer and gastroduodenostomy is performed.

ii. Billroth II gastrectomy:

In Billroth II the antrum and distal part of the body of the stomach is mobilized and resected. The duodenal stump is closed and the distal end of the stomach is anastomosed with loop of jejunum. (Gastrojejunostomy)

iii. Gastrojejunostomy

Gastrojejunostomy was designed because of morbidity and mortality related to and

gastrectomy. In this procedure jejunum is anastomosed with the stomach. In this way reflux of alkali from the small bowel into the stomach occurs which neutralizes the acid and reduces the duodenal exposure of acid. However because of jejunal loop was exposed directly to gastric acid, stomal ulceration was extremely common so this procedure in isolation was abandoned

Vagus denervation and drainage procedures:

Acid production from the stomach is mainly dependent on parasympathetic supply of the stomach (vagus nerve). The vagus nerve fibers are also responsible for transmission of motor impulses to the stomach so the transection of the vagus nerve leads to acid suppression. As the vagus nerve is also responsible for relaxation of pyloric sphincter to allow gastric emptying so vagus denervation also impairs gastric emptying leading to gastric stasis and thus vomiting. This gastric stasis has to be dealt with some sort of drainage procedure (pyloroplasty or gastrojejunostomy) to allow effective gastric emptying/ In pyloroplasty a longitudinal incision is given over the pyloric ring and it is closed transversely, in this way pyloric ring is widened and it allows effective drainage of the stomach as shown below

Vagus Nerve: (Parasympathetic Supply)

• Acid Production

• Pyloric sphincter Relaxation

1. Truncal vagotomy and drainage:

In truncal vagotomy, the anterior and posterior vagus nerves are divided. In this way denervation of the parietal cell causes inhibition of acid secretion. 

The principal of operation is that the section of the vagus nerve reduces the maximal acid output by 50-60% and basal acid output by 90%. The vagus nerve fibers are conductors of motor impulses to the stomach. Denervation of the antro-pyloro-duodenal segment results in gastric stasis so some sort of drainage procedure like pyloroplasty gastrojejunostomy is needed for effective emptying of the stomach.

Nerve supply to liver and intestine is impaired with truncal vagotomy and it leads to gallstone formation and dumping

Gastric Stasis

Gallstone formation

Dumping

2. Selective vagotomy and drainage:

In selective vagotomy the hepatobiliary fibers and branches to the celiac plexus are preserved. In this way supply to the small intestine, liver and  gallbladder is preserved. Chances of gallstone formation and dumping are reduced.

3. Highly selective vagotomy - Gold standard

In highly selective vagotomy the hepatobiliary and antral branches (crow's foot) of the vagus nerve are preserved and only parietal cell mass of the stomach is denervated; drainage of the stomach is not necessary. This procedure is regarded as the gold standard in terms of low side effects, operative mortality and recurrence of PUD.

Surgery for gastric ulcer:

In case of gastric ulcer surgery, diseased tissue is also removed as this has advantage that malignancy can confidently be excluded

Complications of peptic ulcer surgery:

1. Recurrent ulceration:

With all types of peptic ulcer surgery, there are chances of ulcer recurrence.

2. Dumping syndrome:

Dumping syndrome is a group of cardiovascular and gastrointestinal symptoms resulting in rapid pouring of gastric contents into the small intestine because of vagotomy and gastric drainage procedure. Early dumping is essentially due to hypovolemia and late dumping is essentially due to hypoglycemia.

Dumping syndrome occurs in 10% patients after gastric resection or vagotomy.

EARLY DUMPING: - Due to Hypovolemia

Early dumping occurs within 5-45 minutes of eating. Features of early dumping are:

• Sweating

• Palpitations

• Dizziness

• Tachycardia

• Flushing

• Nausea

• Diarrhea

Why early dumping occurs:

Due to resection of distal stomach, denervation and drainage procedures of stomach, all the ingested meal rapidly enters into the small bowel. To digest this food huge flux of bile, pancreatic juice and succuss entericus is produced which causes large fluid shifts and leads to hypovolemia. It tends to improve with time and dietary manipulation is vital in the treatment. Following dietary manipulations should be adapted.

• Small dry meal. Protein Meal

• Avoid fluid during or after meals.

• Avoid high carbohydrate diets; sometimes revision surgery may be required.

LATE DUMPING: -due to hypoglycemia

It is less common and features occur within 2-4 hours of eating.

• Sweating

• Tremors

• Dizziness

• Fainting

• Palpitations

• Prostration

Late dumping occurs due to rebound There is a high level of carbohydrates (due to rapid gastric emptying) in the small bowel. This carbohydrate load in the small bowel causes an increase in plasma glucose level, which in turn, causes hypersecretion of insulin from beta cells of pancreas. This hyper-insulinemia causes secondary hypoglycemia.  Treatment is the same as in early dumping and octreotide is very effective in dealing with it.

3. Alkaline reflux gastritis:

Alkaline reflux (bile) gastritis and esophagitis result from mucosal injury by duodenal Contents (Billroth II and gastrojejunostomy) being refluxed into the stomach. Diagnostic features include chronic, continuous epigastric pain, exacerbated by eating, bilious vomiting,

4. Post vagotomy diarrhea:

Pathophysiology is the same as dumping syndrome. There is rapid emptying of the stomach leading to diarrhea. Treatment is difficult. Antidiarrheal drugs and dietary manipulations are helpful to some extent.

5. Gastric carcinoma:

Incidence of gastric carcinoma increases four times after vagotomy and drainage procedures.

6. Gallstone formation:

Gallstone formation is increased after truncal vagotomy due to denervation of hepatobiliary plexus causing biliary stasis and stone formation. This complication does not occur with selective and highly selective vagotomy.

7. Nutritional Deficiencies:

Nutritional deficiencies occur after gastrectomy e.g.

• Iron deficiency anemia.

• Vitamin B12 deficiency (due to intrinsic factor deficiency)

• Calcium deficiency (Osteoporosis)

• Malabsorption.

• Reduced appetite.

Complications of peptic ulcer:

1. Perforation. (Perforated peptic ulcer)

2. Bleeding.

3. Gastric outlet obstruction.

4. Recurrent ulceration.

1. Perforated peptic ulcer:

Even after widespread use of Antisecretory drugs, perforated peptic ulcer is still a common cause of peritonitis admitted in surgical wards. Patients usually narrate the history of long standing burning epigastric pain or history of intake of NSAIDs. The most common site of perforation is the anterior aspect of the duodenum however anterior or incisural gastric ulcer may perforate and in addition gastric ulcer may perforate into the lesser sac. Perforated peptic ulcer has 10-40% mortality and mortality is increased in the presence of following conditions

• Delay in diagnosis (more than 24 hours)

• Comorbid conditions

• Old age

• Hemodynamically instability

Investigations:

• Diagnosis of perforated peptic ulcer is clinical.

• X-Ray chest in erect posture shows air under diagram in more than 50% of cases

• Leukocytosis.

• USG abdomen shows free fluid in the peritoneal cavity.

• Serum amylase to rule out pancreatitis. Although amylase is also raised to some extent in peptic ulcer but it increases four times of normal in pancreatitis.

• CT scan abdomen is more accurate investigation but is not needed in all cases, it can also differentiate other causes of acute abdomen

Treatment:

Treatment is surgical, but before embarking on surgery it is necessary that the patient should be resuscitated to stabilize the patient hemodynamically. Following steps should be observed while resuscitation.

• Intravenous fluids.

• Nasogastric aspiration.

• Monitor urine output.

• Intravenous antibiotics (cephalosporin, Metronidazole)..

• Analgesics.

• Arrangement of blood.

• Carry out all the investigations required for fitness of anesthesia.

After adequate resuscitation the patient is shifted to the operation theater and general anesthesia is given. Abdomen is opened through upper midline incision. Peritoneal cavity is washed with plenty of normal saline. If the perforation is in the duodenum it can usually closed by applying stitches in transverse direction to avoid pyloric stenosis. It should be remembered that sufficient tissue should be taken in the sutures and they should not be so tight that they cut through the tissue. It is a common practice to place Omental patch over the perforation in order to seal the leak

if any.

If perforation is in the stomach, margins should be refreshed, biopsy from the margin of the ulcer should be obtained to rule out malignancy and perforation is closed. Sometimes when there is massive perforation of duodenum or the stomach, the primary closure may not be possible. In these situations; Billroth II gastrectomy or subtotal gastrectomy should be performed. Post operatively, patients should be given intravenous fluids, electrolytes, antibiotics, analgesics and life long proton pump inhibitors. In cases of H.pylori infection; eradication therapy should also be given. The above mentioned operation can also be performed laparoscopically The patients with small leak from perforated

ulcer and minimal

peptic

contamination

peritoneal

can be managed successfully by

non-operative measures including intravenous

fluids, antibiotics and nasogastric suction

2. Bleeding peptic ulcer:

Bleeding is the most common cause of ulcer related death. Peptic ulcer is responsible for 70% of all upper gastrointestinal bleeding and mortality rate is 5-10%. The incidence of bleeding is more in elderly and in those who are using NSAIDs. Presentations are hematemesis or melena. Bleeding can be minor or severe. Severe bleeding occurs as a result of penetration of duodenal ulcer into gastro duodenal or lesser curvature ulcer into gastro duodenal or lesser curvature ulcer into left gastric artery and early surgical intervention should be considered in these cases.

1. Medical treatment:

   Resuscitation:

• Intravenous proton pump inhibitors.

• Use of tranexamic acid reduces the chances of rebleeding.

• 75% of the patients will stop bleeding with these measures

2. Endoscopic treatment:

Endoscopy is very helpful in the form of cautery, epinephrine injection and clipping

3. Surgical treatment:

Indications:

• Continuous bleeding (patient requiring more than 6 units of blood); unresponsive to endoscopic measures.

• Rebleeding after one or two attempts of endoscopic control.

• Lack of availability of therapeutic endoscopists.

• Visible spurting vessel at base of ulcer on endoscopy.

• Clot at base of ulcer.

The aim of the operation is to stop the bleeding and pre-operative endoscopy may help in localization of the bleeding site.

Patient should be resuscitated. Abdomen opened through upper midline incision. Stomach or duodenum is opened depending upon the suspected site of bleeding. The bleeding vessel in the ulcer is under-run. Biopsy of the ulcer should be obtained if it is in the stomach to exclude malignancy.

Gastric outlet obstruction/Pyloric stenosis:

Pyloric stenosis results from healing of duodenal ulcer, leading to fibrosis and narrowing of its lumen. The most common site of obstruction is the first part of duodenum.

Clinical features:

1. Previous history of acid peptic disease.

2. Effortless and projectile vomiting.

3. Absence of Bile in the vomitus and presence of partially digested food eaten hours or even days before vomiting.

4. Repeated vomiting leads to weight loss, and metabolic derangement.

5. Succussion splash: 

• Due to chronic obstruction, stomach dilates and may sometimes reach up to the pelvis which can be demonstrated on a barium meal.

Treatment:

• Intravenous fluids containing sodium.

• Nasogastric aspiration.

• Correct acid base derangements.

• Early pyloric stenosis may be due to edema and resolves spontaneously.

• Severe cases are treated by endoscopic balloon dilatation or by surgical pyloroplasty/gastrojejunostomy.