TREATMENT

• The aims of management are:

- to relieve symptoms,

- induce ulcer healing in the short term,

- cure the ulcer in the long term.

H. pylori eradication is the cornerstone of therapy for peptic ulcers, as this will successfully prevent relapse and eliminate the need for long-term therapy in the majority of patients.

Before the discovery of H. pylori, the therapy of PUD disease was centered on the old dictum by Schwartz of “no acid, no ulcer.” Although acid secretion is still important in the pathogenesis of PUD, eradication of H. pylori and therapy/prevention of NSAID-induced disease is the mainstay. A summary of commonly used drugs for treatment of acid peptic disorders is shown in Table .

Triple therapy, although effective, has several drawbacks, including the potential for poor patient compliance and drug-induced side effects. Compliance is being addressed somewhat by simplifying the regimens so that patients can take the medications twice a day.

Two anti-H.pylori regimens are available in prepackaged formulation: Prevpac (lansoprazole, clarithromycin, and amoxicillin) and Helidac (bismuth subsalicylate, tetracycline, and metronidazole). The contents of the Prevpac are to be taken twice per day for 14 days, whereas Helidac constituents are taken four times per day with an antisecretory agent (PPI or H₂ blocker), also taken for at least 14 days.

One important concern with treating patients who may not need treatment is the potential for development of antibiotic-resistant strains. The incidence and type of antibiotic-resistant H. pylori strains vary worldwide. Strains resistant to metronidazole, clarithromycin, amoxicillin, and tetracycline have been described, with the latter two being uncommon. Antibiotic-resistant strains are the most common cause for treatment failure in compliant patients. Unfortunately, in vitro resistance does not predict outcome in patients. Culture and sensitivity testing of H. pylori is not performed routinely. Although resistance to metronidazole has been found in as many as 30% and 95% of isolates in North America and Asia, respectively, triple therapy is effective in eradicating the organism in >50% of patients infected with a resistant strain. Clarithromycin resistance is seen in about 10% of persons in the United States.

Failure of H. pylori eradication with triple therapy is usually due to infection with a resistant organism.Quadruple therapy (Table 274-3), where clarithromycin is substituted for metronidazole (or vice versa), should be the next step.

SIDE-EFFECTS of IPP

• Hipergastrinemia

• Diarrhoea

• Headache

• Rashes

• Interection with warfarin, phenytoin, fewer drugs

Side effects of therapy

have been reported in up to 20 to 30% of patients on triple therapy. Bismuth may cause black stools, constipation, or darkening of the tongue. The most feared complication with amoxicillin is pseudomembranous colitis, but this occurs in <1 to 2% of patients. Amoxicillin can also lead to antibiotic-associated diarrhea, nausea, vomiting, skin rash, and allergic reaction. Tetracycline has been reported to cause rashes and very rarely hepatotoxicity and anaphylaxis.

• Prostaglandins exert complex In low doses protect against injury induced by aspirin and NSAIDs by enhancing mucosal blood flow, and by stimulating mucus and bicarbonate secretion and epithelial cell proliferation.

• At high doses acid secretion is inhibited. Misoprostol is effective for the prevention and treatment of NSAID-induced ulcers, but in clinical practice IPP are preferred, since they are at least as effective and have fewer side-effects.

Once an ulcer (GU or DU) is documented, then the main issue at stake is whether H. pylori or an NSAID is involved. With H. pylori present, independent of the NSAID status, triple therapy is recommended for 14 days, followed by continued acid-suppressing drugs (H₂ receptor antagonist or PPIs) for a total of 4 to 6 weeks. Selection of patients for documentation of H. pylori eradication (organisms gone at least 4 weeks after completing antibiotics) is an area of some debate. The test of choice for documenting eradication is the UBT. The stool antigen study may also hold promise for this purpose, but the data have not been as clear cut as in the case of using the stool antigen test for primary diagnosis. Further studies are warranted, but if the UBT is not available, a stool antigen should be considered to document eradication. Serologic testing is not useful for the purpose of documenting eradication since antibody titers fall slowly and often do not become undetectable. Two approaches toward documentation of eradication exist: (1) test for eradication only in individuals with a complicated course or in individuals who are frail or with multisystem disease who would do poorly with an ulcer recurrence, and (2) test all patients for successful eradication. Some recommend that patients with complicated ulcer disease or who are frail should be treated with long-term acid suppression, thus making documentation of H. pylori eradication a moot point. In view of this discrepancy in practice, it would be best to discuss with the patient the different options available.

If the ulcer has closed, but the tests on H.P. stayed positive, recommended

Long-term supported antirelaps therapy

Several issues differentiate the approach to a GU versus a DU. GUs, especially of the body and fundus, have the potential of being malignant. Multiple biopsies of a GU should be taken initially; even if these are negative for neoplasm, repeat endoscopy to document healing at 8 to 12 weeks should be performed, with biopsy if the ulcer is still present. About 70% of GUs eventually found to be malignant undergo significant (usually incomplete) healing.

The majority (>90%) of GUs and DUs heal with the conventional therapy outlined above. A GU that fails to heal after 12 weeks and a DU that does not heal after 8 weeks of therapy should be considered refractory. Once poor compliance and persistent H. pylori infection have been excluded, NSAID use, either inadvertent or surreptitious, must be excluded. In addition, cigarette smoking must be eliminated. For a GU, malignancy must be meticulously excluded. Next, consideration should be given to a gastric hypersecretory state, which can be excluded with gastric acid analysis. Although a subset of patients have gastric acid hypersecretion of unclear etiology as a contributing factor to refractory ulcers, ZES should be excluded with a fasting gastrin or secretin stimulation test (see below). More than 90% of refractory ulcers (either DUs or GUs) heal after 8 weeks of treatment with higher doses of PPI (omeprazole, 40 mg/d; lansoprazole 30 to 60 mg/d). This higher dose is also effective in maintaining remission. Surgical intervention may be a consideration at this point; however, other rare causes of refractory ulcers must be excluded before recommending surgery. Rare etiologies of refractory ulcers that may be diagnosed by gastric or duodenal biopsies include: ischemia, Crohn's disease, amyloidosis, sarcoidosis, lymphoma, eosinophilic gastroenteritis, or infection [cytomegalovirus (CMV), tuberculosis, or syphilis].

COMPLICATION
of peptic ulcer disease

• perforation,

• gastricoutletobstruction

• bleeding.

Surgical Therapy

Surgical intervention in PUD can be viewed as being either elective, for treatment of medically refractory disease, or as urgent/emergent, for the treatment of an ulcer-related complication.

• EMERGENCY

- Perforation

- Haemorrhage

ELECTIVE

- Gastric outflow obstruction

- Recurrent ulcer following gastric surgery

The development of pharmacologic and endoscopic approaches for the treatment of peptic disease has led to a substantial decrease in the number operations needed for this disorder. Refractory ulcers are an exceedingly rare occurrence. Surgery is more often required for treatment of an ulcer-related complication. Gastrointestinal bleeding perforation, and gastric outlet obstruction are the three complications that may require surgical intervention.

Examples of clinical diagnosis:

Duodenal ulcer disease, active study, HP-positive

Date: 2014-12-21; view: 1588