This document provides information on the causes, diagnosis, and management of peptic ulcer disease and gastric outlet obstruction. It discusses that peptic ulcers are caused by an imbalance between aggressive factors like acid secretion and defensive factors. Infection with H. pylori is a key cause. Diagnosis involves endoscopy with biopsy. Management focuses on treating H. pylori infection and using antisecretory drugs. Surgery is reserved for complications or refractory cases. Gastric outlet obstruction is usually due to peptic ulcer disease but can also be caused by malignancy, inflammation, or other conditions.

1. LECTURE 7 Surgery in peptic ulcer disease National O. Bogomolets Medical University Faculty Surgery Department N1 Kyiv 2008 Prof. Kucher M.

2. An ulcer (from Latin ulcus ) is an open sore of the skin, eyes or mucous membrane, often caused, but not exclusively, by an initial abrasion and generally maintained by an inflammation, an infection, and/or medical conditions which impede healing. In other words , it is a macroscopic discontinuity of the normal epithelium (microscopic discontinuity of epithelium is called erosion )

3. Peptic ulcer disease is a common clinical ailment, once thought to be caused by oversecretion of acid and pepsin, an enzyme of the stomach that promotes digestion by breaking down proteins. Researchers have found, however, that although the injury caused by acid and pepsin is necessary for the formation of ulcers, acid secretion levels of the majority of patients with gastric or duodenal ulcers are normal.

4. duodenum ulcer pathogenesis: An ulcer is now known to be the result of an imbalance between aggressive and defensive mechanisms in the stomach and duodenum. Part of that imbalance can be attributed to infection by H. pylori . Altetarion Protection balance

5. H. pylori infection and PUD Barry Marshall and Robin Warren in June 1983 their letter appears in the Lancet 2005 Warren and Marshall are awarded the Nobel Prize in Physiology or Medicine for their work on H. pylori and PUD Humans are the only known host of Helicobacter pylori. Its prevalence in healthy people increases with age to over 50% in people over the age of 60. Incidents of infection increase with decreasing socioeconomic status. H. pylori is spread by close personal contact. However, the exact mechanism for transmission of the bacteria is not well understood.

6. duodenum ulcer pathogenesis: H.Pylori Inflammatory response -> gastritis Stimulate Gastrin production

7. duodenum ulcer pathogenesis: Subsequent Hypersecretion of H + H.Pylori Inflammatory response -> gastritis Stimulate Gastrin production Gastric metaplasia of duodenal mucosa

8. duodenum ulcer pathogenesis: Altetarion Subsequent Hypersecretion of H + Colonization of metaplastic areas H.Pylori Inflammatory response -> gastritis Stimulate Gastrin production Gastric metaplasia of duodenal mucosa

9. duodenum ulcer pathogenesis: Altetarion Protection MUCUS: glycoproteins, water, electrolytes (HCO) Subsequent Hypersecretion of H + Colonization of metaplastic areas H.Pylori Inflammatory response -> gastritis Stimulate Gastrin production Gastric metaplasia of duodenal mucosa

10. duodenum ulcer pathogenesis: Protection MUCUS: glycoproteins, water, electrolytes (HCO) NSAIDs PROSTAGLANDIN E2

11. Etiology Helicobacter pylori Non-steroidal anti-inflammatory drugs (NSAIDs) This group of drugs includes aspirin, ibuprofen and diclofenac. Their role as anti-inflammatory agents centres on their inhibition of prostaglandin synthesis by inhibiting the action of cyclo-oxygenase. In the stomach, prostaglandins are responsible for the production of mucus and bicarbonate. These both help to protect the stomach mucosa from acid by maintaining an alkaline buffer zone. By inhibiting prostaglandin synthesis, NSAIDs damage the gastric mucosa and are implicated in 30% of gastric ulcers. They may also be responsible for the small number of H. pylori-negative duodenal ulcers. Smoking Genetic factors Hyperparathyroidism (Hypercalcemic stimul. of acid secretion) Zollinger-Ellison syndrome This is a rare syndrome caused by a gastrin-secreting tumour (gastrinoma), which is normally found in the pancreas but may occasionally be found in the duodenum or stomach.

12. gastric ulcer pathogenesis H. pylori is found in approximately 75% of cases of gastric ulcers , although its role here is less well defined. It may be that the gastritis facilitates the access of acid and pepsin to the stomach mucosa. It seems that the key factor is decreased mucosal resistance , with excess acid having less of a role. Indeed, most patients with gastric ulceration have a normal or decreased secretory capacity. Duodenum-gastric reflux

13. H.D.Johnson classification of the gastric ulcer Ann Surg. 1965 December; 162(6): 996–1004 Type 1. An ulcer in the body of stomach without of abnormality of the duodenum, pylorus or prepyloric region (usually normal or low acid output) Type 2. An ulcer of the body of stomach combined with, and probably secondary to, an ulcer or its scar in the duodenum (high acid output) Type 3. The gastric ulcer close to the pylorus

14. Modified Johnson classification of gastric ulcers. ( I ) Lesser curve, incisura. ( II ) Body of stomach, incisura + duodenal ulcer (active or healed). ( III ) Prepyloric. ( IV ) High on lesser curve, near gastroesophageal junction. ( V ) Medication induced (nonsteroidal anti-inflammatory drugs/acetylsalicylic acid), anywhere in stomach.

15. Clinical features Recurrent well-localized epigastric pain Classically, the pain of a gastric ulcer occurs during eating and is relieved by vomiting . Patients with duodenal ulceration characteristically describe pain when they are hungry . This pain is relieved by food, antacids, milk and vomiting. Often, however, these well-defined features are not present, and it is usually impossible to differentiate between the pain of gastric ulceration and that of duodenal ulceration. Other symptoms associated with peptic ulcer disease include heartburn, anorexia, waterbrash (a sudden flow of saliva into the mouth) and intolerance of certain foods. Intermittent vomiting may occur. Where persistent vomiting is troublesome, the possibility of gastric outlet obstruction should be considered.

16. Differential diagnosis Medical Gastro-oesophageal reflux disease Myocardial infarction Pulmonary embolism Lower lobe pneumonia Irritable bowel syndrome Surgical Biliary colic or acute cholecystitis Pancreatitis Mesenteric ischaemia Perforation of a viscus Acute appendicitis Gastro-oesophageal malignancy

17. Diagnosis Endoscopy is now preferred to contrast studies in the investigation of peptic ulcer disease. It allows good visualization and biopsy of lesions and the detection of H. pylori using the CLO test. Contrast studies are still used where endoscopy is contraindicated, e.g. the use of Gastromiro studies in suspected perforation. They have no role as a first-line investigation for uncomplicated disease . Ultrasound may be useful to exclude coexistent pathology LAB The full blood count may indicate iron-deficiency anaemia in the patient with a chronically bleeding ulcer. The bio-chemical screen may reveal dehydration and hypokalaemia from vomiting. Where hypergastrinaemia is suspected (e.g. Zollinger-Ellison syndrome), serum gastrin should be estimated. Calcium may be elevated in patients with hyperparathyroidism. Measurement of gastric acid secretion , pentagastrin (BAO/MAO) Niw in use only for Z-E and peptic ulcer recurrenceevaluation

18. MANAGEMENT OF UNCOMPLICATED PEPTIC ULCER DISEASE Surgery has become outdated, its use now being limited to patients in whom malignancy has been proven, and those in whom complications, e.g. bleeding, perforation or stenosis , have developed. General measures include: Avoidance of NSAIDs, smoking and excessive alcohol. Antisecretory agent selective histamine receptor antagonists, or proton pump inhibitors (PPIs). e.g. omeprazole or lansoprazole supplement antisecretory agents include bismuth compounds, sucralfate, prostaglandin analogues and antacids Eradication of H. pylori

19. Table 1 -- Treatment Regimens for Helicobacter pylori Eradication Triple Therapies Bismuth subsalicylate 525mg QID + Metronidazole 250mg QID + Tetracycline 500mg QID Proton pump inhibitor BID + Amoxicillin 1000mg BID + Clarithromycin 500mg BID Quadruple Therapy Bismuth subsalicylate 525mg QID + Proton pump inhibitor BID + Metronidazole 250mg QID + Tetracycline 500mg QID

20. Duodenal Ulcer indications for surgery Intractable : parietal cell vagotomy Bleeding : truncal vagotomy with pyloroplasty and oversewing of bleeding vessel Perforation : patch closure with treatment of H. pylori with or without parietal cell vagotomy Obstruction : rule out malignancy and parietal cell vagotomy with gastrojejunostomy

21. Truncal Vagotomy + Heineke-Mikulicz pyloroplasty

22. Highly Selective Vagotomy (Parietal Cell Vagotomy)

23. Gastric Ulcer indications for surgery Intractable • Type I: distal gastrectomy with Billroth I • Type II or III: distal gastrectomy with truncal vagotomy Bleeding • Type I: distal gastrectomy with Billroth I • Type II or III: distal gastrectomy with truncal vagotomy Perforated • Type I, stable: distal gastrectomy with Billroth I • Type I, unstable: biopsy, patch, and treatment for H. pylori • Type II or III: patch closure with treatment of H. pylori Obstruction : rule out malignancy and antrectomy with vagotomy Type IV: depends on ulcer size, distance from the gastroesophageal junction, and degree of surrounding inflammation (special procedures) Giant gastric ulcers: distal gastrectomy, with vagotomy reserved for type II and III gastric ulcers

24. Differential Diagnosis in Intractable Gastric Ulcer • Cancer • Persistent Helicobacter pylori • Resistant organisms • Poor patient compliance • Occult use of nonsteroidal anti-inflammatory drugs/acetylsalicylic acid • Motility disorder • Zollinger-Ellison syndrome

25. B1 and BII gastrectomy

26. Ludwik Rydygier In 1880, second in the world he succeeded in surgical removal of pylorus from patient suffering from stomach cancer. He was also first to document this procedure. In 1881, as the first in the world, he carried peptic ulcer resection. In 1884 he introduced new method of surgical peptic ulcer treatment using Gastroenterostomy. Rydygier was also inventor (1900) of original conception of removing prostatic adenoma and many other surgical techniques.

27. Operations for high-lying ulcers near the gastroesophageal junction (type IV)

28. COMPLICATIONS OF PEPTIC ULCERATION REQUIRING OPERATIVE INTERVENTION

29. PERFORATION Duodenal ulcers. Up to 50% of patients will have had no previous ulcer symptoms. The incidence of duodenal ulcer perforation is decreasing, probably due in part to improvements in the medical management of duodenal ulcers. Perforation usually occurs in acute ulcers on the anterior wall of the duodenum. Gastric ulcers. Gastric ulcer perforation is less common than duodenal ulcer perforation. It has a peak incidence in the elderly, and consequently the associated morbidity and mortality are higher. Gastric perforation has a strong association with NSAID use.

30. PERFORATION Clinical features The acute onset of severe unremitting epigastric pain is strongly suggestive of the possibility of perforation. Thereafter, the range of symptoms depends on the intra-abdominal course The patient may be pale, shocked and peripherally shut down secondary to generalized peritonitis . Irritant stomach contents in the peritoneal cavity may give rise to shoulder-tip pain , resulting from irritation of the diaphragm. Vomiting may occur. The abdomen does not move freely with respiration, and marked tenderness , guarding, fear of movement and board-like rigidity Respiration is shallow and bowel sounds are usually absent. Generalized peritonitis does not occur in some patients because the perforation seals over with omentum. In others, the fluid tracks down the right paracolic gutter, simulating acute appendicitis . Silent perforations may also occur, and are only found incidentally on a chest X-ray.

31. PERFORATION n 60% of cases of perforation, an erect chest X-ray will demonstrate free air under the diaphragm, although the absence of free air does not exclude a perforation A moderate hyperamylasaemia may be found with a perforated duodenal ulcer. High amylase levels are more suggestive of pancreatitis. Where there is still doubt over the diagnosis, an emergency water-soluble contrast meal or an abdominal CT scan may be indicated.

32. PERFORATION Management The initial management, as for other causes of peritonitis, consists of resuscitation, oxygen, intravenous fluids and antibiotics (e.g. cefuroxime and metronidazole) passage of a nasogastric tube adequate analgesia and antiemetics should be given as necessary urinary catheter enables close monitoring of urine output. Operative management is indicated in most patients, but rapid operative intervention should not be substituted for thorough resuscitation. Although a laparoscopic approach to treatment is favoured by some, its superiority over open surgery is yet to be established

33. PERFORATION Duodenal ulcers. Surgery usually involves simple closure All patients should be given eradication therapy. In some cases, there may be a place for the non-operative management of perforated ulcers. This may be appropriate in patients with silent perforations and those too ill to undergo laparotomy (e.g. due to severe cardiorespiratory disease). Where the decision has been made not to operate, management consists of supportive treatment with nasogastric suction, H. pylori eradication therapy, intravenous fluids and antisecretory agents. Close supervision of the patient is necessary, as evidence of clinical deterioration suggests failure of conservative treatment. Gastric ulcers. Approximately 15% of perforated gastric ulcers prove ultimately to be malignant . However, current practice suggests biopsy of the ulcer wall, followed by simple closure or local excision of the ulcer, is best. If the ulcer turns out to be malignant, a minority will progress to gastric resection following tumour staging

34. PYLORIC STENOSIS Pyloric stenosis consists of narrowing of the pyloric channel, leading to gastric outlet obstruction. The obstruction may be anywhere in the region of the pylorus, but most commonly occurs in the first part of the duodenum. The most common cause in adults is peptic ulceration

35. PYLORIC STENOSIS Clinical features Gastric outlet obstruction presents with symptoms of fullness and often a constant dull pain in the epigastrium. Projectile vomiting of large volumes of undigested and partially digested food matter is characteristic. This is more common later in the day and when lying down, and usually relieves the sensation of fullness. There may be associated weight loss. On examination there is commonly epigastric fullness associated with signs of dehydration and weight loss. Visible gastric peristalsis may be seen and is diagnostic of gastric outlet obstruction. A succussion splash (i.e. an audible splashing noise when the patient is gently rocked from side to side) is often elicited

36. PYLORIC STENOSIS CAUSES OF GASTRIC OUTLET OBSTRUCTION Peptic ulcer disease Malignancy Stomach antrum Pancreas Lymphomas Crohn's disease of duodenum Adult hypertrophic pyloric stenosis Inflammation of adjacent organs Gastroparesis

37. PYLORIC STENOSIS Management When gastric outlet obstruction is suspected, large-bore nasogastric tube is passed. Often, large volumes of non-bilious gastric contents can be aspirated and undigested food may be recognized. Intravenous access is obtained and bloods sent for full blood count, urea and electrolytes. Biochemical analysis usually reflects dehydration, with a low sodium, potassium and chloride and a high urea and bicarbonate. Gastric outlet obstruction is further investigated using radiological contrast studies (e.g. barium meal) or Endoscopy is the investigation of choice, as biopsies can establish the nature of the obstruction.

38. PYLORIC STENOSIS In most patients there is no indication for urgent laparotomy and their fluid and electrolyte balance should be corrected prior to any surgery. In long-standing cases, there may also be some benefit from intravenous feeding prior to surgery to improve the patient's overall nutritional status Surgery is not always necessary and, assuming the pathology is benign, a course of PPIs may be sufficient to heal the ulceration and relieve the obstruction. Where surgery is necessary and where the pathology is benign pyloroplasty or gastrojejunostomy may suffice, but antrectomy is a more reliable operation to minimize the risk of ulcer recurrence Where malignancy is identified, more radical surgery may be necessary.

39. ACUTE HAEMORRHAGE Upper gastrointestinal bleeding presents with haematemesis (vomiting blood) and/or melaena (the passage of black tarry stool that has a very characteristic smell). Melaena results from the digestion of blood by enzymes and bacteria.

40. ACUTE HAEMORRHAGE CAUSES OF UPPER GASTROINTESTINAL BLEEDING Peptic ulceration 50% Mucosal lesions ( gastritis d uodenitis and erosions ) 30% Mallory-Weiss tear 5-10% Varices 5-10% Reflux oesophagitis 5% Angiodysplasia 2% Carcinoma Uncommon Aortoduodenal fistula Uncommon Dieulafoy syndrome Rare (rupture of a large tortuous submucosal artery normally found in the body of the stomach) Coagulopathies Uncommo n

41. ACUTE HAEMORRHAGE Diagnosis History Pointers to the diagnosis include the past medical history (peptic ulcer disease, previous bleeding, liver disease, previous surgery, coagulopathies) drug history (most importantly, NSAIDs and anticoagulants) social history (alcohol abuse). Specific features to be looked for include those suggestive of acute substantial blood loss and shock (hypotension, tachycardia, tachypnoea and pallor) and signs of liver disease and portal hypertension (spider naevi, portosystemic shunting and bruising)

42. ACUTE HAEMORRHAGE Diagnosis Blood tests The full blood count may be normal immediately after an acute bleed but will fall once haemodilution has occurred. The test may show anaemia, suggestive of more chronic blood loss Urea is often high following a gastrointestinal bleed, due to the absorption of blood and its subsequent metabolism by the liver Coagulation derangement occurs in the presence of significant liver disease.

43. ACUTE HAEMORRHAGE Management Resuscitation administration of high-flow oxygen intravenous access is obtained and blood taken for the investigations noted above a sample is also taken for blood cross-matching and intravenous fluids started. A nasogastric tube is passed to monitor the bleeding and prevent aspiration. A urinary catheter is inserted. A central or arterial line may aid resuscitation. Volume replacement is gauged against pulse, blood pressure, urine output and central venous pressure. Over-transfusion or rapid transfusion in those with compromised cardiac function can lead to pulmonary oedema.

44. ACUTE HAEMORRHAGE Once resuscitation has stabilized the patient, endoscopy is used to detect the site of bleeding The aims of management of bleeding peptic ulcers are: to identify the bleeding point arrest the bleeding (bleeding ceases spontaneously in 90% of patients) prevent recurrence.

45. ACUTE HAEMORRHAGE FORREST – endoscopic classification of upper gastrointestinal hemorrhage Acute hemorrhage Forrest I a Arterial, spurting hemorrhage Forrest I b Oozing hemorrhage Signs of recent hemorrhage Forrest II a g = vessel < 2mm Visible vessel G = vessel > 2mm Forrest II b Adherent clot Forrest II c Hematin- covered lesion Lesions without active bleeding Forrest III No signs of recent hemorrhage Forrest J.A.,Finlayson N.D. “Endoscopy in gastrointestinal bleeding.” Lancet, 1974, N11, p.394-399

46. endoscopic treatment: vessel clipping

47. Doppler-based injection treatment is superior to endoscopic treatment based exclusively on the Forrest classification. Doppler-based local endoscopic treatment reduced the danger of a rebleed and thus the number of emergency operations and the overall mortality.

48. Factors Predicting Failure of Nonoperative Management of Bleeding Duodenal Ulcer Hemodynamic instability Significant comorbid conditions Transfusion requirements greater than 4–6 units in 24 hours Endoscopic features of the ulcer Actively bleeding vessel Visible vessel Adherent clotSize >2cm

49. ACUTE HAEMORRHAGE Surgical management Emergency surgery may be indicated if endoscopy reveals: bleeding from a major artery where attempted injection sclerotherapy is unable to control the bleeding directly; 50% of patients with active arterial bleeding and 30% with a visible vessel at the ulcer base are ultimately likely to require surgery.

50. ACUTE HAEMORRHAGE Surgical management Duodenal ulcers A bleeding duodenal ulcer may simply be under-run with sutures, through a duodenotomy (opening of the anterior wall of the duodenum) to gain access to the ulcer. Once tolerating oral fluids, the patient should be started on H. pylori eradication therapy empirically.

51. ACUTE HAEMORRHAGE Surgical management Gastric ulcers. With a bleeding gastric ulcer, the possibility of malignancy must be considered. The ulcer must be biopsied in all cases to determine its nature. In young fit patients, the ulcer should be excised completely by taking a small wedge resection. In elderly patients or those with significant comorbidity, under-running of the ulcer may be preferable, at least in the first instance. If the pathology result confirms malignancy, then the patient should have accurate staging and further treatment as indicated. If the ulcer proves to be benign, H. pylori eradication is indicated. NSAIDs should be avoided.

54. Biology of Helicobacter pylori Helicobacter are Gram-negative, aerobic or microaerophilic, spiral-shaped bacilli that are motile by way of flagella at one end of the cell. Closely related to Helicobacter are species of the genera Aquaspirillum, Azospirillum, Spirillum, and Camplyobacter. The genetics of Helicobacter pylori are complex; there are many strains of H . pylori which are distinguished by the human disease with which they are associated. Once Helicobacter pylori colonizes its host, it lives in the interface between the surface of gastric epithelial cells and the overlying mucus gel layer, often clustering at the junctions of epithelial cells. In addition H. pylori can also be found on top of the gastric epithelium in the duodenum and esophagus. It was not until 1983 that H. pylori was recognized as having any medical importance. Now, it has been proven that H. pylori infection is the main cause of chronic superficial gastritis and it is associated with both gastric and duodenal ulcers. Still, researchers are not sure how H. pylori escapes the bactericidal effects of gastric acid, or how it colonizes the gastric mucosa and damages the gastric epithelial cells. H. pylori produces urease, which leads to the formation of ammonia on the gastric mucosa, thereby increasing the pH of its environment. The organism also releases cytotoxins, toxic proteins, platelet activating factor, and lipopolysaccharide. the latter is overproduced in its outer membrane. Colonization of the stomach by H. pylori leads to an inflammatory response that is mediated by several of the bacterium's virulence determinants, which ultimately cause injury to the stomach tissues.

55. Camplyobacter-like organism (CLO) test. This test is based on the fact that mucosal biopsy specimens can be inoculated into a medium containing urea and phenol red, a dye that turns pink in a pH of 6.0 or greater. The pH will rise above 6.0 when H. pylori, the Campylobacter-like organism, metabolizes urea to ammonia by way of its urease activity. This test is commercially available and therefore quite inexpensive. Only one-half hour is required for diagnosis of infection, and the test has shown 98% sensitivity and 100% specificity. These qualities have made the CLO test the invasive technique of choice for diagnosing H. pylori infection. Noninvasive Techniques Breath test. Although H. pylori itself can not be detected noninvasively, its urease activity can be detected by way of a breath test. In this test, urea that is radioactively labeled with carbon 13 and carbon 14 is ingested. Bacterial urease splits off labeled carbon dioxide, which can be detected in the breath. Accuracy is not a problem for either of these breath tests, since both elicit 100% sensitivity and specificity. The breath test technique reflects only current infection with H. pylori but can demonstrate very rapidly the existence of infection. A disadvantage of this technique is that it may involve a small amount of exposure to radiation. Although carbon 13 is a stable isotope and does not emit radiation, its detection requires a mass spectrometer, which may not readily available. The breath test is not yet commercially available. Detection of IgG antibody. When a host recognizes H. pylori an immune response immediately stimulates IgG and secretory antibody IgA. Therefore, serologic testing for antibodies to H. pylori using the enzyme-linked immunosorbent assay (ELISA) has become a widely accepted diagnostic test. The test is simple, inexpensive, and readily available. ELISA detects IgG with a sensitivity of up to 99% and is 100% specific. Since spontaneous clearing of H. pylori by lgG or IgA is rare, an elevated antibody titer indicates current infection. This test also detects the decline in antibody titer after removal of the organism; however, the rate of decline of IgG after eradication is still not known. This technique, although useful and accurate, still has certain limitations. In order to determine a clear decline in antibody titer, the patient must be monitored for at least six months, and the cutoff for a significant decline is unclear. In addition, in order to control the inherent variability of the test, the base and follow-up titer must be measured simultaneously. Still, the outstanding accuracy and low cost makes this test an attractive choice for detecting H. pylori infection. In current practice, endoscopy is still required for diagnosis of infection by Helicobacter pylori. The full range of noninvasive techniques is expected to be more readily available soon, with the antibody tests ideal for assessing current infection, and the carbon 13-urea breath test the method of choice for determining the response to infection.

56. The intensity of the host immune responses can culminate in one of several ways: The most common result is chronic superficial gastritis, which is an inflammation of the stomach lining due to the infiltration of lymphocytes, plasma cells, eosinophils, and monocytes into the mucosal lining of the stomach, which causes injury to the gastric glands. The immune response can actually benefit H. pylori by releasing nutrients locally for the organism. The host could be harmed by the immune response due to the direct damage of epithelial cells, which affects their function and vitality. The host, in order to avoid this type of cell damage, will often down-regulate its immune response, making it even more difficult to completely eliminate H. pylori from the affected area. The immune response can also cause inflammation of the duodenum, leading to duodenal ulcers. Atrophic gastritis,which is a nonspecific inflammation of the entire lining of the stomach, may be the result of the infiltration of lymphocytes into the stomach. MALT-type and other lymphomas, which are tumors of the mucosal and lymphoid tissues, can also result from H. pylori infection. The effects of infection by Helicobacter pylori represent a delicate equilibrium between the host's inability to remove the organism and its ability to contain the damage caused by the pathogen. It is the integrity of this equilibrium that allows H. pylori to persist in most cases for a lifetime in their hosts

57. Triple Therapy Eradication of Helicobacter pylori is defined as the absence of the organism four or more weeks after eradication therapy. Since the eradication rate for single-drug therapy is only 19% and that for double-drug therapy is still only 48%, researchers have found that combining three antibiotics offers a better chance for eliminating the bacterium. The highest eradication rate, 82%, was achieved by combining: bismuth, metronidazole, and tetracycline. There are obvious drawbacks to this type of treatment. First of all, it is inconvenient for the patient, so it is difficult for doctors to convince their patients to comply with the therapy. Second, such multidrug therapy is almost always associated with many adverse side effects, namely diarrhea, nausea, and vomiting, which occur in approximately 20% of all patients.

58. SPECIAL FORMS OF ULCERATION Stress ulceration refers to erosions or ulceration of the stomach or duodenum occurring in certain circumstances. These include severe illness, trauma, prolonged mechanical ventilation, multiple organ failure, sepsis and major surgery. The aetiology is not fully defined, although acid and mucosal ischaemia appear to be key elements. Medical prophylaxis using proton pump inhibitors may be useful in such circumstances. Cushing's and Curling's ulcers are special forms of stress ulceration that occur following central nervous injury and burns, respectively. Hypersecretion of acid is not always essential for stress ulceration to occur, but does appear to be important in both of these conditions. In neurosurgical injury, raised intracranial pressure may be responsible for an increase in vagal activity and hence the increase in gastric secretion. The ulcers resulting from hypersecretion are usually single and, in common with other forms of peptic ulceration, may be complicated by perforation and bleeding.