Peptic Ulcer Disease Treatment and Management
Common Very strong association with Helicobacter pylori (present in 95 of duodenal and 70-80 of gastric ulcers), NSAID use. Rare Zollinger-Ellison syndrome. Common. Annual incidence is about 1-4 1000. More common in males. Duodenal ulcers have a mean age in the thirties, while gastric ulcers have a mean Symptoms have a variable relationship to food (e.g. if worse soon after eating, more likely to be gastric ulcers if worse several hours later, more likely to be duodenal). I Bloods FBC (for anaemia), amylase (to exclude pancreatitis), U&Es, clotting screen (if GI bleeding), LFT, crossmatch if actively bleeding. Endoscopy Four quadrant gastric ulcer biopsies to rule out malignancy duodenal ulcers need not be biopsied. Peptic ulcer continued 155 Overall lifetime risk 10 . Generally good as peptic ulcers associated with H. pylori can be cured by eradication.
There is important evidence to document the involvement of Helicobacter pylori as a causative agent of peptic ulcer disease, antral atrophic gastritis, gastric adenocarcinoma and gastric lymphoma (Konturek et al. 2006a,b). Although these diseases are much more common in adulthood, colonization with this pathogen occurs mostly during Peptic ulcer disease is much less common in the pediatric population than in adulthood. The classification of peptic ulcers is based on the region of involvement (gastric versus duodenal ulcers) and on the presence or absence of a known etiology (primary or secondary due to an underlying disease). Primary peptic ulcers are associated with H. pylori infection. Gastric ulcers are mostly seen in neonates (with or without the development of gastric perforation) while duodenal ulcers are much more common after the neonatal period. Drumm et al. (2004) demonstrated that single-contrast barium studies have a high false-negative rate for ulcer disease, when...
Diseases which affect gastric motility and emptying are predominantly diseases of the gastrointestinal tract itself, disorders involving smooth muscle and extraintestinal diseases. Some diseases only affect one of the phases of gastric emptying. Generally duodenal ulcer produces accelerated emptying, while gastric ulcer reduces antral motility, producing normal emptying of liquids but delayed emptying of solids50. Emptying of a solid meal is slowed in patients with pernicious anaemia51 and atrophic gastritis52, but in achlorhydric patients liquids empty rapidly53.
Acute and or chronic lesions on the gastric mucosa may result from the ingestion of alcohol, and some drugs such as anti-inflammatory drugs, reserpine, histamine and caffeine. Salicylates are often reported to produce dyspepsia and gastric ulcers due to their widespread use. A single dose of 2 aspirin tablets produced haemorrhaging in the stomach of normal volunteers within 1 hour of ingestion, continued intake (2 tablets every 6 hours) resulted in gastric erosions in all subjects and duodenal erosions in 50 of the subjects104. Patients who require aspirin on a regular basis should take enteric coated or adequately buffered preparations.
Gastroduodenal Higher morbidity and mortality in perforated gastric ulcers than duodenal perforated gastric carcinomas have a very poor prognosis. Large bowel Untreated colonic perforation has a high risk of faecal peritonitis and death from septicaemia and multiorgan failure.
A relatively safe drug like famotidine or ranitidine may be classified as prescription-only in one country because experts in that country consider its indications (gastric ulcers or esophageal reflux) to be dangerous for people to treat without medical attention. In another country this issue may not be considered as important, and the drug may be classified as nonprescription.
H. pylori is a Gram-negative, microaerophilic bacterium that selectively colonizes the human stomach. The current prevalence of infection is 30-40 in the United States and substantially higher in underdeveloped regions. H. pylori induces a vigorous mucosal immune response that fails to eradicate the organism, resulting in chronic gastritis that can lead to peptic ulcers, gastric adenocarcinoma, and gastric lymphoma. In addition to a chronic lymphocyte response, there is an activation of the innate immune response in monocytes and macrophages in particular, and recruitment of neutrophils. Our lab has focused on mechanisms whereby the innate immune response is dysregu-lated, and we have directly implicated polyamines in these events.
Adult parasites burrow into the duodenojejunal mucosa and may cause abdominal pain, usually epigastric and usually worsened by food ingestion this may mimic peptic ulcer disease. Nausea, vomiting, bloating and abdominal dis-tention may be additional features. Abdominal tenderness, especially epigastric, is the most common abnormality on physical examination (Milder et al., 1981). Cramping lower abdominal pain may be associated with intermittent or persistent diarrhoea. Malabsorption can be a complication in severe infection (Liu and Weller, 1993). Necrotising jejunitis, arteriomesenteric occlusion and small bowel infarct are unusual complications (Lee and Terry, 1989). Upper and lower gastrointestinal bleeding are rare complications (Bhatt et al., 1990).
Bloom and Jacobs studied the cost effects of prescribing restrictions on peptic ulcer disease (PUD) in the West Virginia Medicaid program during 1982, using a before-after comparative design.30 They found that total Med-icaid costs for PUD treatment were 15 lower during a period when a restrictive formulary was in effect than during a period when an open formulary was in effect. However, this overall 15 savings was explained by a sharp decline in the number of patients receiving care under the Med-icaid program for PUD. The cost per member per month (PMPM) for PUD patients actually increased 9.4 . Furthermore, although pharmacy costs fell by 80 , physician costs increased by 3.1 and inpatient hospital costs increased by 24 .30
Selye's general adaptation syndrome involves three stages of physiological response alarm, resistance, and exhaustion. During the alarm stage, the organism detects a stressor and responds with SNS and hormonal activation. The second stage, resistance, is characterized by the body's efforts to neutralize the effects of the stressor. Such attempts are meant to return the body to a state of homeostasis, or balance. (The concept of homeostasis, or the tendency of the body to seek to achieve an optimal, adaptive level of activity, was developed earlier by Walter Cannon.) Finally, if the resistance stage is prolonged, exhaustion occurs, which can result in illness. Selye referred to such illnesses as diseases of adaptation. In this category of diseases, he included hypertension, cardiovascular disease, kidney disease, peptic ulcer, hyperthyroidism, and asthma.
Gastric ulcers Gastritis and gastric ulcers may rarely develop in the proximal gastric pouch. Gastric ulceration after GBP is a rare complication. Ulcers have also been reported to occur in the distal stomach and may lead to perforation (Fig. 3.76). The classic sign of free intraperitoneal air may not
Of in vitro dissolution tests however this is often not the case. Endoscopy has demonstrated that when multiple tablets are administered, all lie in the same place in the stomach, at the base of the greater curvature. This is a particular problem with formulations which cause gastric irritation or damage, for example non-steroidal anti-inflammatory drugs which can produce focal erosions due to repeated insult to a small area of the mucosa. Iatrogenically-produced ulcers can often be differentiated from those of natural origin, since drug-induced erosions usually occur at the base of the greater curvature, whereas peptic ulcers form on the lesser curvature. Multiple unit dose forms can also cause mucosal damage for example microencapsulated potassium chloride showed similar gastric mucosal irritation to single units. This was attributed to poor dispersion of the potassium chloride, with clumps of the drug held together with gastric mucus64.
The concept of stress has been used to help explain the etiology of certain diseases. Diseases that are thought to be caused in part by exposure to stress or poor ability to cope with stress are called psychophysiological or psychosomatic disorders. Among the diseases that seem to have strong psychological components are ulcers and coronary heart disease. The role of stress in ulcers was highlighted in a study by Joseph V. Brady known as the executive monkey study. In this study, pairs of monkeys were yoked together in a restraining apparatus. The monkeys received identical treatment except that one member of each pair could anticipate whether both of them would be shocked (it was given a warning signal) and could control whether the shock was actually administered (if it pressed a lever, the shock was avoided). Thus, one monkey in each pair (the executive monkey ) had to make decisions constantly and was responsible for the welfare of both itself and its partner. Twelve pairs of...
Oesophageal varices, hiatus hernia, peptic ulcer, aspirin ingestion, hookworm, hereditary telangiectasia, carcinoma of the stomach, caecum or colon, ulcerative colitis, angiodysplasia, Meckel's diverticulum, diverticulosis, haemorrhoids, etc. Haematuria (e.g. renal or bladder lesion), haemoglobinuria (e.g. paroxysmal nocturnal haemoglobinuria) Overt haemoptysis, idiopathic pulmonary haemosiderosis
Cannot be coped with effectively can have severe negative consequences. Work by pioneering stress researchers such as Hans Selye brought attention to the physiological changes produced by exposure to chronic stress, which contribute to diseases such as peptic ulcers, high blood pressure, and cardiovascular disorders. Subsequent research by psychiatrists Thomas Holmes and Richard Rahe and their colleagues indicated that exposure to a relatively large number of stressful life events is associated with the onset of other diseases, such as cancer and psychiatric disorders, which are less directly a function of arousal in specific physiological systems.
Rapid detection by real-time PCR has been an important advantage where early diagnosis and appropriate antibiotic therapy are vital for survival, and traditional methods are often time-consuming. For instance, the early detection of bacterial DNA in the blood of critically ill patients with traditional culture diagnostic is still technically difficult (Cursons et al., 1999). Real-time PCR assays have been developed for quantification of different bacteria, including Chlamydia pneumoniae in human atherosclerotic plaques (Ciervo et al., 2003), intestinal bacterial populations (Ott et al., 2004) and Streptococcus pneumoniae in nasopharyngeal secretions (Saukkoriipi et al., 2004). Helicobacter pylori is considered to be the major causative agent of gastritis in acute or chronic forms and an important factor for etiology of peptic ulcer and gastric cancer. Real-time PCR technique based on the amplification of a fragment of the 23S rRNA gene has been developed (Lascols et al., 2003). This...
Large bowel Most common Diverticulitis and colorectal carcinoma (80 ), a perforated appendix is a common complication of appendicitis. Others Volvulus, ulcerative colitis (toxic megacolon), trauma, radiation enteritis and complications of post-op anastomotic dehiscence or colonosopy. Gastroduodenal Most common Perforated duodenal or gastric ulcer, more rarely gastric carcinoma (1-2 ). perforated peptic ulcer). Gastroduodenal Laparotomy and peritoneal lavage the perforation is closed and an omental patch placed. Gastric ulcers should be biopsied (four quadrant, frozen section if possible) to examine for carcinoma. Closure is more difficult than duodenal ulcers and Billroth I partial gastrectomy with gastroduodenal anastomosis can be done. Post-op H. pylori eradication if positive. Oesophageal Depends on pathology and time of presentation. If occurs during dilation of a malignant stricture, coverage by an expandable stent may be possible. If spontaneous and
Operations of the stomach have evolved greatly since Billroth first described the partial gastrectomy in 1881. General indications for gastric surgery include resection of neoplasms, peptic ulcer disease (PUD), and obesity. Various factors, including decreased incidence of PUD and evolving medical therapy for it, have contributed to an overall decrease in the amount of gastric surgery being performed. Radiographic contrast examinations remain the most useful means of evaluating early and late complications of gastroduodenal surgery.
Studies related to safety pharmacology (sometimes confusingly termed 'general pharmacology' studies) tend now also to be performed earlier in the drug development process than was previously the case. While in some respects considered an aspect of the discipline of pharmacology, the purpose of safety pharmacology is to evaluate the potential pharmacological properties that may be unrelated to the intended indication for the drug. An example of this would be significant effects of a drug on the cardiovascular system that may actually be under development for the treatment of gastric ulcers.
What are the main clinical manifestations of gastric cancer nowadays In other words, what should be changed and what should be added to the known clinical symptoms In the clinical diagnosis of early gastric cancer it is necessary to consider the patient's age and the presence of the symptom of rapid satiability while taking food. It should be noted that this symptom, which is more characteristic of advanced gastric cancers, can also occur in the early stages. True, this symptom may be discovered only by very thorough observation of the patient by a gastroenterologist or general clinician, or else by the family doctor. A further symptom is transient epigastric pain which rapidly subsides in response to the treatment of endoscopically diagnosed gastritis or peptic ulcer.
Clinical symptoms become more pronounced in the presence of ulceration. This helps in the differentiation of non-differentiated and signet-ring cell carcinoma from the great variety of other forms, among which infiltrative cancers dominate. The clinical picture of the disease depends mainly on infiltra-tive-ulcerous carcinomas, which now prevail. This, in turn, interferes with the differential diagnosis of malignant and benign ulcers. Ulcer in the anamnesis makes a clinical diagnosis even more difficult. Correct diagnostic and therapeutic tactics are therefore decisive for the prognosis. According to some authors, symptoms specific for peptic ulcer are absent 117, 177 . This means that if epigastric discomfort and pain intensify after meals, and the feeling of full stomach, nausea, and vomiting develop, this suggests a very high probability of malignancy (O Fig. 24).
But the list of potential complications associated with the clinical use of TRPV1 antagonists does not stop here. Expression of TRPV1 is up-regulated in the rat stomach after chemical (HCl) injury this mechanism is supposed to be protective against mucosal damage 166 . In fact, capsazepine was shown to aggravate HCl-induced gastric ulcers 167 . This phenomenon may prevent the oral use of TRPV1 antagonists that are absorbed in the stomach. Furthermore, TRPV1 is present on rat islet beta cells, where it plays a role in insulin secretion 168 . TRPV1 is also expressed in human brain endothelium where its function remains to be determined 169 . Last, an area of special concern is the enigmatic presence of TRPV1 throughout the whole neuroaxis of the rat 170 . Recently, it was suggested that TRPV1 antagonists may impact on behaviours including anxiety and affect 171 .
Those with ascites, e.g. liver cirrhosis (SBP) or children with nephrotic syndrome. Seconday generalised peritonitis Peritonitis due to bacterial translocation and spread, evolving from a localised focus (see above) or nonbacterial due to spillage of bile, blood, gastric contents, e.g. perforated peptic ulcer, pancreatic
A gastroenterostomy, usually gastrojejunostomy, may be performed as a drainage procedure with vagotomy for peptic ulcer disease and in patients with unresectable antral carcinomas and other conditions that may lead to antral narrowing, such as Crohn's disease. In the past, simple gastroenterostomy was a commonly performed procedure for PUD, although it was abandoned owing to the high ulcer recurrence rate. An anastomosis is generally made between the jejunum and the greater curvature of the stomach, as far as possible from the pylorus, in a side-to-side fashion, although other configurations are sometimes used (Figs. 3.35 and 3.36). The jejunum may be brought either to the anterior wall of the stomach superior to the omentum or to the