PEPTIC ULCER DISEASE
Estimates of the incidence of uncomplicated peptic ulcer disease range from 0.09 to 0.3 percent per patient-year.(1,2) A systematic review of the literature covering developed countries estimated that the annual incidence ranged from 0.1 to 0.19 percent for physician-diagnosed PUD and 0.01 to 0.17 percent when based upon hospitalized patients.(3)
Age adjusted rates showed that approximately 0.7/10,000 population of males and 0.3/10,000 population of females might be suffering from gastric ulcer in Karachi. Duration of symptoms varied from 1-288 months (median 6 months).(4)
Peptic ulcers are defects in the gastric or duodenal mucosa that extend through the muscularis mucosa. The epithelial cells of the stomach and duodenum secrete mucus in response to irritation of the epithelial lining and as a result of cholinergic stimulation. The superficial portion of the gastric and duodenal mucosa exists in the form of a gel layer, which is impermeable to acid and pepsin. Other gastric and duodenal cells secrete bicarbonate, which aids in buffering acid that lies near the mucosa. Prostaglandins of the E type (PGE) have an important protective role, because PGE increases the production of both bicarbonate and the mucous layer.
In the event of acid and pepsin entering the epithelial cells, additional mechanisms are in place to reduce injury. Within the epithelial cells, ion pumps in the basolateral cell membrane help to regulate intracellular pH by removing excess hydrogen ions. Through the process of restitution, healthy cells migrate to the site of injury. Mucosal blood flow removes acid that diffuses through the injured mucosa and provides bicarbonate to the surface epithelial cells.
Under normal conditions, a physiologic balance exists between gastric acid secretion and gastroduodenal mucosal defense. Mucosal injury and, thus, peptic ulcer occur when the balance between the aggressive factors and the defensive mechanisms is disrupted. Aggressive factors, such as NSAIDs, H.pylori infection, alcohol, bile salts, acid, and pepsin, can alter the mucosal defense by allowing back diffusion of hydrogen ions and subsequent epithelial cell injury. The defensive mechanisms include tight intercellular junctions, mucus, mucosal blood flow, cellular restitution, and epithelial renewal.
The gram-negative spirochete H.pylori was first linked to gastritis in 1983. Since then, further study of H.pylori has revealed that it is a major part of the triad, which includes acid and pepsin that contributes to primary peptic ulcer disease. The unique microbiologic characteristics of this organism, such as urease production, allows it to alkalinize its microenvironment and survive for years in the hostile acidic environment of the stomach, where it causes mucosal inflammation and, in some individuals, worsens the severity of peptic ulcer disease.
When H.pylori colonizes the gastric mucosa, inflammation usually results. The causal association between H.pylori gastritis and duodenal ulceration is now well established in the adult and pediatric literature. In patients infected with H.pylori, high levels of gastrin and pepsinogen and reduced levels of somatostatin have been measured. In infected patients, exposure of the duodenum to acid is increased. Virulence factors produced by H.pylori, including urease, catalase, vacuolating cytotoxin, and lipopolysaccharide, are well described.
Most patients with duodenal ulcers have impaired duodenal bicarbonate secretion, which has also proven to be caused by H.pylori because its eradication reverses the defect.(5) The combination of increased gastric acid secretion and reduced duodenal bicarbonate secretion lowers the pH in the duodenum, which promotes the development of gastric metaplasia (i.e. the presence of gastric epithelium in the first portion of the duodenum). H.pylori infection in areas of gastric metaplasia induces duodenitis and enhances the susceptibility to acid injury, thereby predisposing to duodenal ulcers. Duodenal colonization by H.pylori was found to be a highly significant predictor of subsequent development of duodenal ulcers in one study that followed 181 patients with endoscopy-negative, nonulcer dyspepsia.(6)
The natural history of peptic ulcer ranges from resolution without intervention to the development of complications with the potential for significant morbidity and mortality, such as bleeding and perforation.
SIGN AND SYMPTOMS:
Obtaining a medical history, especially for peptic ulcer disease, H.pylori infection, ingestion of NSAIDs, or smoking, is essential in making the correct diagnosis. Gastric and duodenal ulcers usually cannot be differentiated based on history alone, although some findings may be suggestive.
Epigastric pain is the most common symptom of both gastric and duodenal ulcers. It is characterized by a gnawing or burning sensation and occurs after meals—classically, shortly after meals with gastric ulcer and 2-3 hours afterward with duodenal ulcer. Food or antacids relieve the pain of duodenal ulcers but provide minimal relief of gastric ulcer pain.
Duodenal ulcer pain often awakens the patient at night. About 50-80% of patients with duodenal ulcers experience nightly pain, as opposed to only 30-40% of patients with gastric ulcers and 20-40% of patients with nonulcer dyspepsia (NUD). Pain typically follows a daily pattern specific to the patient. Pain with radiation to the back is suggestive of a posterior penetrating gastric ulcer complicated by pancreatitis.
Other possible manifestations include the following:
- Dyspepsia, including belching, bloating, distention, and fatty food intolerance
- Chest discomfort
- Hematemesis or melena resulting from gastrointestinal bleeding. Melena may be intermittent over several days or multiple episodes in a single day.
- Rarely, a briskly bleeding ulcer can present as hematochezia
- Symptoms consistent with anemia (e.g. fatigue, dyspnea) may be present
- Sudden onset of symptoms may indicate perforation
- NSAID-induced gastritis or ulcers may be silent, especially in elderly patients.
Testing for H.pylori infection is essential in all patients with peptic ulcers. In most patients with uncomplicated peptic ulcer disease (PUD), routine laboratory tests usually are not helpful. Documentation of PUD depends on radiographic and endoscopic confirmation.
If the diagnosis of PUD is suspected, obtaining CBC count, liver function tests (LFTs), amylase, and lipase may be useful. CBC count and iron studies can help detect anemia, which is an alarm signal that mandates early endoscopy to rule out other sources of chronic GI blood loss
Testing for H.pylori infection is essential in all patients with peptic ulcers.
Endoscopic or invasive tests for H.pylori include a rapid urease test, histopathology, and culture. Rapid urease tests are considered the endoscopic diagnostic test of choice. The presence of H.pylori in gastric mucosal biopsy specimens is detected by testing for the bacterial product urease. Fecal antigen testing identifies active H.pylori infection by detecting the presence of H.pylori antigens in stools. This test is more accurate than antibody testing and is less expensive than urea breath tests.
Upper GI endoscopy is the preferred diagnostic test in the evaluation of patients with suspected PUD. It is highly sensitive for the diagnosis of gastric and duodenal ulcers, allows for biopsies and cytologic brushings in the setting of a gastric ulcer to differentiate a benign ulcer from a malignant lesion, and allows for the detection of H.pylori infection with antral biopsies for a rapid urease test and/or histopathology in patients with PUD.
In patients presenting acutely, a chest radiograph may be useful to detect free abdominal air when perforation is suspected. On upper GI contrast study with water-soluble contrast, the extravasation of contrast indicates gastric perforation.
Angiography may be necessary in patients with a massive GI bleed in whom endoscopy cannot be performed. An ongoing bleeding rate of 0.5 mL/min or more is needed for the angiography to be able to accurately identify the bleeding source. Angiography can depict the source of the bleeding and can help provide needed therapy in the form of a direct injection of vasoconstrictive agents.
SERUM GASTRIN LEVEL:
A fasting serum gastrin level should be obtained in certain cases to screen for Zollinger-Ellison syndrome.
A single biopsy offers 70% accuracy in diagnosing gastric cancer, but 7 biopsy samples obtained from the base and ulcer margins increase the sensitivity to 99%. Brush cytology has been shown to increase the biopsy yield, and this method may be useful particularly when bleeding is a concern in a patient with coagulopathy.
The histology of gastric ulcer depends on its chronicity. The surface is covered with slough and inflammatory debris. Beneath this neutrophilic infiltration, active granulation with mononuclear leukocytic infiltration and fibrinoid necrosis may be seen. In chronic superficial gastritis, lymphocytes, monocytes, and plasma cells often infiltrate the mucosa and submucosa.
PATIENT SELECTION FOR TREATMENT:
Treatment of peptic ulcers varies depending on the etiology and clinical presentation. The initial management of a stable patient with dyspepsia differs from the management of an unstable patient with upper GI hemorrhage. In the latter scenario, failure of medical management not uncommonly leads to surgical intervention.
Treatment options include empiric antisecretory therapy, empiric triple therapy for H.pylori infection, endoscopy followed by appropriate therapy based on findings, and H.pylori serology followed by triple therapy for patients who are infected. Breath testing for active H.pylori infection may be used.
Endoscopy is required to document healing of gastric ulcers and to rule out gastric cancer.
Specific clinical recommendations are as follows:
- Patients with peptic ulcers who are older than 55 years, have alarm symptoms, or have ulcers that fail to respond to treatment should promptly undergo upper endoscopy (level of evidence, A).
- To facilitate healing and to decrease the risk for recurrence of gastric and duodenal ulcers, pylorishould be eradicated in patients with peptic ulcer disease (level of evidence, A).
- PPIs offer suppression of acid secretion, healing, and symptom relief in patients with peptic ulcers that are superior to those associated with other antisecretory therapies (level of evidence, A).
- Patients with bleeding peptic ulcers should be treated with a PPI to decrease the need for transfusions or surgery and to reduce the duration of hospital stay. Those with bleeding peptic ulcers and positive pylori testing should have eradication therapy prescribed (level of evidence, A).
- Patients with perforated ulcers should undergo eradication of coexisting pyloriinfection. Successful eradication should reduce the need for long-term antisecretory therapy and additional surgery (level of evidence, C).
Bleeding Peptic Ulcers
The principles of management of bleeding peptic ulcers outlined below are equally applicable to both gastric and duodenal ulcers.
Upper GI bleeding secondary to a bleeding peptic ulcer is a common medical condition. Endoscopic evaluation of the bleeding ulcer can decrease the duration of the hospital stay by identifying patients at low risk for rebleeding. Moreover, endoscopic therapy reduces the likelihood of recurrent bleeding and decreases the need for surgery.
Patients can be stratified as having high or low risk for rebleeding depending on the presence or absence of stigmata seen on the initial endoscopic examination.
High-risk stigmata are the following:
- Active hemorrhage (90% risk of rebleeding)
- A visible vessel (50% risk of rebleeding)
- A fresh overlying clot (30% risk of rebleeding)
Ulcers with such stigmata require endo therapy, while ulcers with a clean base need not be treated endoscopically. In the absence of these stigmata, patients can be discharged home on medical therapy within 48 hours.
Acid suppression is the general pharmacologic principle of medical management of acute bleeding from a peptic ulcer. Reducing gastric acidity is believed to improve hemostasis primarily through the decreased activity of pepsin in the presence of a more alkaline environment. Pepsin is believed to antagonize the hemostatic process by degrading fibrin clots. By suppressing acid production and maintaining a pH above 6, pepsin becomes markedly less active. Concomitant H.pylori infection in the setting of bleeding peptic ulcers should be eradicated, as this lowers the rate of rebleeding.(7, 8)
Two classes of acid-suppressing medications currently in use are histamine-2 receptor antagonists (strongRAs) and proton pump inhibitors (PPIs).(9) Both classes are available in intravenous and oral preparations. Examples of strongRAs include ranitidine, cimetidine, famotidine, and nizatidine. Examples of PPIs include omeprazole, pantoprazole, lansoprazole, and rabeprazole.
strongRAs are an older class of medications, and in the setting of an actively bleeding duodenal ulcer, their use has been largely superseded by the use of PPIs. Many gastroenterologists assert that intravenous PPI therapy maintains hemostasis more effectively than intravenous strongRA. Thus, intravenous strongRA no longer has a role in the management of bleeding peptic ulcers.(10)
In the United States, the recommended primary therapy for H.pylori infection is proton pump inhibitor (PPI)–based triple therapy.(11) These regimens result in a cure of infection and ulcer healing in approximately 85-90% of cases.(12) Ulcers can recur in the absence of successful H.pylori eradication.
PPI-based triple therapy regimens for H.pylori consist of a PPI, amoxicillin, and clarithromycin for 7-14 days. A longer duration of treatment (14 d vs 7 d) appears to be more effective and is currently the recommended treatment. Amoxicillin should be replaced with metronidazole in penicillin-allergic patients only, because of the high rate of metronidazole resistance.(13) In patients with complicated ulcers caused by H.pylori, treatment with a PPI beyond the 14-day course of antibiotics and until the confirmation of the eradication of H.pylori is recommended.
PPI-based triple therapies are a 14-day regimen as shown below:
Omeprazole: 20 mg PO bid or Lansoprazole: 30 mg PO bid or
Rabeprazole: 20 mg PO bid Or Esomeprazole: 40 mg PO qd
Clarithromycin: 500 mg PO bid and Amoxicillin: 1 g PO bid
Quadruple therapies for H.pylori infection are generally reserved for patients in whom the standard course of treatment has failed.
Quadruple treatment includes the following drugs, administered for 14 days:
- PPI, standard dose, or ranitidine 150 mg, PO bid
- Bismuth 525 mg PO qid
- Metronidazole 500 mg PO qid
- Tetracycline 500 mg PO qid
Consider maintenance therapy with half of the standard doses of strong-receptor antagonists at bedtime in patients with recurrent, refractory, or complicated ulcers, particularly if cure of H.pylori has not been documented or if an H.pylori –negative ulcer is present.
NSAID’s Induced Ulcers
In 2009, the American College of Gastroenterology (ACG) issued a guideline for prevention of NSAID-related ulcer complications.(14) According to the ACG guideline, all patients who are beginning long-term NSAID therapy should first be tested for H.pylori. NSAIDs should be immediately discontinued in patients with positive H.pylori test results if clinically feasible.
For patients who must continue with their NSAIDs, PPI maintenance is recommended to prevent recurrences even after eradication of H.pylori.(15,16) If NSAIDs must be continued, changing to a COX-2 selective inhibitor is an option. However, use of a traditional NSAID and once-daily PPI is comparable to a selective COX-2 inhibitor with respect to ulcer bleeding in patients with a history of peptic ulcer disease.(17) In general, 6-8 weeks of therapy with a PPI is required for complete healing of a duodenal ulcer.
Active ulcers associated with NSAID use are treated with an appropriate course of PPI therapy and the cessation of NSAIDs. For patients with a known history of ulcer and in whom NSAID use is unavoidable, the lowest possible dose and duration of the NSAID and co-therapy with a PPI or misoprostol are recommended.
DETERRENCE AND PREVENTION:
Primary prevention of NSAID-induced ulcers includes the following:
- Avoid unnecessary use of NSAIDs
- Use acetaminophen or nonacetylated salicylates when possible
- Use the lowest effective dose of an NSAID and switch to less toxic NSAIDs, such as the newer NSAIDs or cyclooxygenase-2 (COX-2) inhibitors, in high-risk patients without cardiovascular disease.
Prophylactic regimens that have been shown to dramatically reduce the risk of NSAID-induced gastric and duodenal ulcers include the use of a prostaglandin analog or a PPI according to the following regimens:
- Misoprostol 100-200 mcg PO 4 times per day
- Omeprazole 20-40 mg PO every day
- Lansoprazole 15-30 mg PO every day
SURGICAL CARE FOR PERFORATED PEPTIC ULCERS:
With the success of medical therapy, surgery has a very limited role in the management of PUD. Elective peptic ulcer surgery has been virtually abandoned. In the 1980s, the number of elective operations for peptic ulcer disease dropped more than 70%, and emergent operations accounted for more than 80%.(18) In general, 5% of bleeding ulcers eventually require operative management. The indications for urgent surgery include the following:
- Failure to achieve hemostasis endoscopically
- Recurrent bleeding despite endoscopic attempts at achieving hemostasis (many advocate surgery after 2 failed endoscopic attempts)
The appropriate surgical procedure depends on the location and nature of the ulcer. Many authorities recommend simple over sewing of the ulcer with treatment of the underlying H.pylori infection or cessation of NSAIDs for bleeding PUD. Additional surgical options for refractory or complicated PUD include vagotomy and pyloroplasty, vagotomy and antrectomy with gastroduodenal reconstruction (Billroth I) or gastrojejunal reconstruction (Billroth II), or a highly selective vagotomy.
GOALS OF THERAPY:
The goal of treatment for peptic ulcer disease is to:
- Relieve symptoms
- Heal lesions
- Prevent recurrences
- Prevent complications
Treatment for PUD is based on guidelines from the prestigious societies.
To review the guidelines of American college of gastroenterology for prevention of NSAID-related ulcer complications, click on the link below
To review the guidelines of American college of gastroenterology for the management of H.Pylori Infection
LONG TERM MONITORING:
Maintenance therapy with antisecretory medications (e.g. strong blockers, PPIs) for 1 year is indicated in high-risk patients. High-risk patients include those with recurrent ulcers and those with complicated or giant ulcers. If H.pylori eradication is not achieved despite repeat treatment, maintenance antisecretory therapy should be recommended.
Consider maintenance therapy with half of the standard doses of strong-receptor antagonists at bedtime in patients with recurrent, refractory, or complicated ulcers, particularly if cure of H.pylori has not been documented or if an H.pylori –negative ulcer is present.
Patients with refractory ulcers may continue receiving once-daily PPI therapy indefinitely. In this setting, if H.pylori is absent, consider a secondary cause of duodenal ulcer, such as Zollinger-Ellison syndrome.
Peptic ulcer rebleeding is extremely rare after H.pylori eradication. The use of maintenance antisecretory therapy is not necessary if H.pylori eradication has been achieved. However, NSAID use may cause rebleeding even in patients in whom H.pylori has been eradicated.(19)
CONSULTATION AND COUNSELING:
Patients should be warned of known or potentially injurious drugs and agents. Some examples are as follows:
- Caffeine (e.g. coffee, tea, colas)
Obesity has been shown to have an association with peptic ulcer disease (PUD), and patients should be counseled regarding benefits of weight loss. Stress reduction counseling might be helpful in individual cases but is not needed routinely.
Eat meals on time
It is very important for ulcer patients to take all meals on time and avoid snacking at odd times of the day between meals. Stomach acid is produced in response to food in order to digest it. Eating on time tunes the body into releasing the right amount of digestive juice at the right time. On the other hand, eating at odd times, such as between the meals, leads to overproduction of stomach acid. Therefore, ulcer patients are advised to take care of their meal timings and avoid cravings.
Caffeine is a popular stimulant found in a wide variety of food items. The highest content of the compound is found in tea, coffee and chocolate. The patients of ulcer are advised to avoid taking caffeine since it aggravates pain in case of stomach ulcer. Excessive intake of this compound also causes acid reflux and heartburn both of which are painful symptoms associated with the disease. Therefore, in order to prevent this extreme discomfort, ulcer patients should cut down their intake of food items and beverages which contain caffeine. At the onset of the disease, caffeine intake should be completely avoided for a couple of months. As the condition improves through medication, patients may enjoy a cup of coffee or tea in a day or small amounts of other food items containing caffeine.
Give up alcohol
Individuals suffering from stomach ulcer should completely give up alcohol. It stimulates the production of acid in the stomach, thereby causing more damage to the stomach walls and increasing the associated pain. Alcohol may not cause any discomfort right away. However, patients mostly notice the effect around a day after the intake of alcohol. Therefore, it can lead to long term damage unless ulcer patients completely give up their intake of alcoholic beverages.
Avoid hot spices
Although spicy food may not cause ulcers, it does aggravate the pain. Strong spices, such as red chilies, curry powder, mustard and black pepper should therefore be avoided. Hot, spicy meals can lead to acid reflux and indigestion which can be very painful for the sufferers of stomach ulcer. The condition can become worse despite on-going treatment and medications. Therefore, it is advised to reduce the content of strong spices during the preparation of meals for the victims of this disease.
Reduce salt intake
The intake of sodium chloride – table salt – poses health risk in several ways. It has also been proved to be bad for the victims of stomach ulcer. A number of studies have been conducted with the conclusion that a high salt intake worsens the condition. Therefore, along with a reduced intake of strong spices, ulcer patients are also advised to avoid a high intake of salt.
Avoid chewing gum
The process of chewing food is known as mastication in scientific language. This process stimulates the production of gastric juices for the digestion of food as it passes down the alimentary canal. Chewing gum produces the same effect by leading to the production of stomach acid. However, since there is no food to digest, the acid damages the walls of the stomach. Therefore, the act of chewing gum can lead to the formation of ulcers and make the already existing condition worse.
Avoid fatty food
It is very important to maintain the overall health of the digestive system in order to avoid further complications in the case of stomach ulcer. Food items which stimulate the overproduction of digestive juice should be avoided. At the top of the list are fatty foods. In addition, food with a high content of simple sugars should also be avoided.
Stress may not be a cause of the disease, but it has been linked to increased discomfort and pain. Individuals who face mental stress and excessive physical exertion in their daily life experience a slower healing time. Due to this reason, ulcer patients must find a way for reducing their level of stress.
It has long been believed that milk helps in healing ulcer since it alleviates the associated pain. However, milk soothes the pain only for the time being as it coats the lining of the digestive tract. Actually, it leads to more damage and pain since it stimulates the secretion of digestive juices. Ulcer patients should not, therefore, turn to a glass of milk to relieve their pain.
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- Lin KJ, García Rodríguez LA, Hernández-Díaz S. Systematic review of peptic ulcer disease incidence rates: do studies without validation provide reliable estimates? Pharmacoepidemiol Drug Saf 2011; 20:718.
- Sung JJ, Kuipers EJ, El-Serag HB. Systematic review: the global incidence and prevalence of peptic ulcer disease. Aliment Pharmacol Ther 2009; 29:938.
- Sung JJ, Tsoi KK, Ma TK, Yung MY, Lau JY, Chiu PW. Causes of mortality in patients with peptic ulcer bleeding: a prospective cohort study of 10,428 cases.Am J Gastroenterol. 2010 Jan. 105(1):84-9
- Pietroiusti A, Luzzi I, Gomez MJ, Magrini A, Bergamaschi A, Forlini A, et al. Helicobacter pylori duodenal colonization is a strong risk factor for the development of duodenal ulcer.Aliment Pharmacol Ther. 2005 Apr 1. 21(7):909-15.
- Kikkawa A, Iwakiri R, Ootani H, Ootani A, Fujise T, Sakata Y, et al. Prevention of the rehaemorrhage of bleeding peptic ulcers: effects of Helicobacter pylori eradication and acid suppression.Aliment Pharmacol Ther. 2005 Jun. 21 Suppl 2:79-84.
- Gisbert JP, Calvet X, Feu F, Bory F, Cosme A, Almela P, et al. Eradication of Helicobacter pylori for the prevention of peptic ulcer rebleeding.Helicobacter. 2007 Aug. 12(4):279-86.
- Bopar.ai V, Rajagopalan J, Triadafilopoulos G. Guide to the use of proton pump inhibitors in adult patients.Drugs. 2008. 68(7):925-47.
- Barkun A, Bardou M, Marshall JK. Consensus recommendations for managing patients with nonvariceal upper gastrointestinal bleeding.Ann Intern Med. 2003 Nov 18. 139(10):843-57.
- Chey WD, Wong BC. American College of Gastroenterology guideline on the management of Helicobacter pylori infection.Am J Gastroenterol. 2007 Aug. 102(8):1808-25.
- Javid G, Zargar SA, U-Saif R, Khan BA, Yatoo GN, Shah AH, et al. Comparison of p.o. or i.v. proton pump inhibitors on 72-h intragastric pH in bleeding peptic ulcer.J Gastroenterol Hepatol. 2009 Jul. 24(7):1236-43.
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- Lai KC, Lam SK, Chu KM, Wong BC, Hui WM, Hu WH, et al. Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use.N Engl J Med. 2002 Jun 27. 346(26):2033-8.
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