Peptic Ulcer Disease Treatment and Management
The debate between those who favour placebo controlled trials and those who do not is a debate between goal-based thinkers who would always use a placebo unless there were compelling reasons not to, and duty-based thinkers who would only use a placebo if there was no alternative. Writing in favour of the use of placebo controls for trials into treatments of peptic ulcer disease, Ciociola and others (1996) provide some powerful arguments on the goal-based side. There are plenty of 'proven, available' treatments for peptic ulcer disease. Hence, from a duty-based perspective, no trial of new treatments should have placebo comparators, because to deny people with the disease a treatment which was available would be to act against their best interests. But, argues Ciociola, placebo therapy is effective in 48 to 58 of cases of peptic ulcer disease. What that means is that giving dummy substances to people with peptic ulcers has resulted in about half of them getting better. In a trial...
Zollinger-Ellison syndrome (ZES) is characterized by severe hypersecretion of gastric acid, refractory peptic ulcer disease localized to the stomach and the upper gastrointestinal tract, malabsorption, and diarrhea, which is sometimes severe. Nausea, vomiting, and heartburn are present in about 35 of the cases. Approximately 25 of ZES patients present with bleeding. These are primarily patients with the sporadic form of the disease and not those with multiple endocrine neoplasia type 1 (MEN1). ZES is often associated with MEN1, a genetic dominant autosomal disorder due to mutations (over 25 have been documented) in the MEN1 gene on exon 10 of chromosome 11q13. The syndrome involves neoplasia in the parathyroid, pancreatic islet endocrine tumors, pituitary adenomas, and adrenal adenomas. The main pancreatic manifestation of MEN1 is a gastrinoma leading to hypersecretion of gastrin and its physiological consequences. ZES is the major cause of morbidity and mortality in MEN1. The ZES...
Medical disorders associated with an elevated risk of suicide are AIDS, cancer (especially head and neck), Huntington disease, multiple sclerosis, peptic ulcer disease, end-stage renal disease, spinal cord injury, and systemic lupus erythematosus. Any serious medical illness can raise the risk of suicide in elderly Caucasian men. In most cases, suicide in the context of a medical disorder occurs in conjunction with a depressive disorder or a history of alcohol abuse, or both.
Surgeons save lives and heal the sick with their own hands. Surgery is the ultimate curative therapy for many patients and is an essential part of modern medicine. It is a career of constant excitement, high energy, quick decisions, and intellectual stimulation. No day is the same as the one before, and you learn to expect the unexpected. It is extremely gratifying to see the immediate results of your actions the changes you make in your patients' anatomy and in the quality of their lives. Whether you are interested in performing open-heart surgery or repairing perforated peptic ulcers, you must first go through rigorous training in general surgery the foundation and entry point for all areas of this branch of medicine. Some continue to practice as general surgeons others move on to advanced training and become surgical subspecialists like cardiothoracic, pediatric, or vascular surgeons.
Epigastric pain, often aggravated by hunger or by meals and relieved by antacids, suggests peptic ulceration or gastritis. There may be nausea, vomiting and anorexia. Anaemia may develop from chronic haemorrhage. Peptic ulcer may cause major acute bleeding, leading to haemateme-sis and or melaena, which is a medical emergency. Similarly, peptic ulcers may perforate the stomach or duodenum, causing peritonitis. Peptic ulcer may penetrate into the pancreas and cause pancreatitis. Scarring of the duodenum by chronic ulceration may cause intestinal obstruction.
In considering the issue of scientific rigour the use of placebo controls in therapeutic research was discussed. The arguments on both sides were investigated, seeing how a goal-based thinker, such as Ciociola, tries to show that the scientifically rigorous trial is also in accordance with a duty-based ethic, because patients would come to no real harm and could be excluded if there was any possibility that they would. We saw how a duty-based thinker, such as Freedman, tries to show that trials which honour the duty of care to patients can also be scientifically rigorous. Examples of trials in which the use of placebo was contentious were looked at folic acid in pregnancy trials of peptic ulcer disease and ondansetron trials. It was noted in conclusion that whilst goal-based and duty-based approaches might reach out to each other, they do not, in fact, meet in the middle. It was suggested that for this reason it was important to put the duty-based duty of care in primary place, but at...
The commonest lesions treated endoscopically are bleeding peptic ulcers, which can be injected with epinephrine (adrenaline) to cause vasospasm, and ruptured oesophageal varices, which can be injected with sclerosant or ligated with rubber bands to halt bleeding and cause fibrosis and subsequent obliteration. Other bleeding lesions may be treated using lasers or electrocautery.
Infections with H. pylori result in acute and chronic gastric inflammation, which, when untreated, can lead to peptic ulcers or stomach carcinoma. The majority of cases of gastric and duodenal ulcers are caused by H. pylori. The outcome of infection with H. pylori depends on a variety of bacterial, host, and environmental factors.
Helicobacter pylori A type of bacteria that can cause digestive illnesses, including inflammation and infection of the stomach lining, and peptic ulcer (sores on the lining of the stomach or small intestine). Experts believe that most such infections produce no symptoms, so a child can have an infection without knowing it. When the bacteria do cause symptoms, they are usually either symptoms of gastritis or peptic ulcer disease. scientists suspect that H. pylori infection may be contagious, because the infection seems to run in families and is more common where people live in crowded or unsanitary conditions. In children, symptoms of gastritis may include nausea, vomiting, and pain in the abdomen, in addition to stomach ulcers. In older children, the most common symptom of stomach ulcers is a gnawing or burning pain in the abdomen, usually in the area below the ribs and above the navel. This pain typically gets worse on an empty stomach and improves with food, milk, or an antacid...
Cimetidine A drug that blocks the action of histamine (H-2), a substance secreted by mast cells, and thus inhibits the ability of the stomach to make acid. once acid production is decreased, the body is able to heal itself. Benefits include control of hypersecretory stomach disorders and effective treatment of peptic ulcer disease, reflux esophagi-tis, and heartburn. The drug has been shown to have some stimulating effects on the immune system and has been proposed as a treatment for the immune suppression associated with HIV. (The trade name is Tagamet.) ciprofloxacin (Cipro) An oral antibiotic approved for the treatment of many common bacterial infections. It is sometimes administered to treat mac in combination with other drugs. Possible side effects include gastrointestinal upset, seizures, and rash. concomitant administration of antacids like Mylanta or Amphogel that contain aluminum or magnesium hydroxide can lead to the formation of insoluble chelates (heterocyclic chemical...
In the phase III colorectal cancer trial, gastrointestinal perforations were seen in 6 patients out of approx 400 patients in the Avastin + IFL arm compared with none in the IFL-alone arm (7). These events were rare, and predisposing factors for this infrequent condition have not been identified because of the small numbers. The cases were heterogeneous in nature, ranging from a perforated stomach ulcer, to hemorrhage in the setting of carcinomatosis, to abscess. There was only one fatality out of these six patients and efforts are underway in other metastatic colorectal cancer trials to learn more about this rare condition.
DNA sequence studies also identified a related group of transporters in several bacterial pathogens of humans that function not to export DNA but rather to secrete protein toxins (Fig. 2.4). Bordetella pertussis, the causative agent of whooping cough, uses the Ptl transporter to export the six-subunit pertussis toxin across the bacterial envelope. All nine Ptl proteins have been shown to be related to VirB proteins, and the ptl genes and the corresponding virB genes are colinear in their respective operons. Type I strains of Helicobacter pylori, the causative agent of peptic ulcer disease and a risk factor for development of gastric adenocarcinoma, contain a 40-kb cag pathogenicity island (PAI) that codes for several virulence factors, of which several are related to Vir proteins. These Cag proteins are thought to assemble into a transporter for
Including the promoter for RANTES (-403 G A) and a 32 bp deletion in its receptor CCR5 (A32). Using questionnaire data obtained by in-person interviews and germ-line DNA collected in our population-based case-control study of pancreatic cancer, we conducted an analysis of cytok-ine chemokine gene polymorphisms (TNF-a, RANTES, and CCR5) as risk factors for pancreatic cancer.127 We used mass spectrometry and gel-based methods to genotype 308 cases and 964 population-based controls. We assessed potential interactions between these polymorphisms and pro-inflammatory conditions such as pancreatitis, ulcer, tobacco smoking, and other pro-inflammatory genes (gene-gene interactions) as risk factors for pancreatic cancer.127 There was no overall association between pancreatic cancer risk and TNF-a, RANTES, and CCR5 polymorphisms, nor was there evidence for two-locus interactions between these genes. However, among pancreatic cancer cases, we observed elevated OR estimates for TNF-a -308 (GA +...
The differential diagnosis of Zollinger-Ellison syndrome is complicated by a number of factors. Patients usually present with bouts of diarrhea (sometimes bloody), cramps, and weight loss. These may also be attributed to other diseases involving malabsorption such as celiac disease, Crohn's syndrome, pancreatic insufficiency, and bacterial overgrowth syndrome (which results in bile acid loss). In addition, in peptic ulcer patients the use of proton pump inhibitors substantially delays the diagnosis as gastric acid secretion is inhibited and thus many of the identifying symptoms of ZES become muted. When gastrin concentrations are between 50 and 1000 pg mL, the diagnosis of ZES cannot be ruled out, and a secretin challenge test is suggested. The procedure for this test is as follows. A test dose of secretin (SecreFlo) 0.2 mg (0.1 mL) is given IV to test for possible allergies. If no untoward reactions occur, 0.4 mg kg of SecreFlo is administered IV over one minute (bolus). Blood...
Finally, the question has been raised as to whether excessive stress can predispose to neurodegenerative disease. When an animal or human is stressed, one of the things that happens is an increased release of glucocorticoids from the adrenal glands. In the short term glucocorticoids are helpful to a stressed animal. Among other things, they promote the breakdown of protein to glucose, helping to make fat available for use and increasing blood flow. With prolonged stress and a prolonged release, the glucocor-ticoids can have damaging effects, including increased blood pressure, gastric ulcers, and depression of the immune system.
The study doesn't prove that the microbes cause the plaques to build up. Indeed, the antibiotic might have been beneficial because it exerted an anti-inflammatory effect apart from its antibacterial action. Larger-scale antibiotic trials have not shown a reduction in heart attack rates. More research is needed, but if C. pneumoniae does pan out as an agent of inflammation, scientists may one day add antibiotics to their arsenal of standard treatments for coronary artery disease. Other bacteria, including the one that causes stomach ulcers, are also being studied for a link to heart disease.
Duodenal disorders may cause epigastric pain, diarrhoea, malabsorption, loss of weight and nutritional deficiencies. Bleeding ulcers may cause anaemia, haematemesis and melaena, the characteristic black tarry appearance of stool caused by partially digested blood. Cancer of the duodenum is extremely rare, while peptic ulcer and coeliac disease are common (see Chapters 31 & 35).
It is clear that the patient described above suffered from multiple afflictions, but even after the laboratory notified the attending physician of the extremely high gastrin concentrations, in the expiration summary only the presence of diarrhea, cramps, and peptic ulcer disease are noted. No mention is made of the possible presence of ZES. The rarity of this disease was probably the reason for this oversight by the physicians. Yet, all the important signs and symptoms were present, in both the clinical presentation and the laboratory results. The consequences of this disease are severe and may be fatal, as is the case for many rare diseases, but when considered as part of the differential diagnosis, this fatal cascade can be arrested.
Another cause of stomach pain in HIV-positive people is Helicobacter pylori, the bacterium that has been shown to be the cause of stomach ulcers. When HIV disease reaches a later stage, Helicobacter pylori that has until then been under control or unnoticed often flares up. Endoscopy reveals whether it is the bacterium causing the discomfort.
The findings on endoscopy included erythematous gastropathy, a 2-cm clean-based gastric ulcer in the body (Fig. 45.1), and a patulous antrum concerning for prior healed ulcers. Figure 45.1 Gastric ulcer, as seen during endoscopy. (Courtesy of Dr. Dayna Early.) Figure 45.1 Gastric ulcer, as seen during endoscopy. (Courtesy of Dr. Dayna Early.) Figure 45.3 Healing gastric ulcer. (Courtesy of Dr. Dayna Early.) Figure 45.3 Healing gastric ulcer. (Courtesy of Dr. Dayna Early.)
Helicobacter pylori infection tends to reduce gastric acid secretion, particularly when it causes chronic gastritis, so that, theoretically, eradication of H. pylori infection, which reduces the risk of gastritis, peptic ulcer and gastric cancer, may actually exacerbate acid reflux (see Chapter 31).
Many patients with pancreatic endocrine tumors present with signs and symptoms of excess hormone secretion. Clinical manifestations of the most common endocrine tumor, an insulinoma, are profound hypoglycemia with diaphoresis, confusion, and syncope. Classically, gastrinomas are the second most common tumor of islet-cell origin, and they present with peptic ulcer disease. Other common symptoms include diarrhea and esophagitis.
Most of the older NSAIDs inhibit both COX-1 and COX-2 and thus have anti-inflammatory and antiplatelet effects and increase the risk of peptic ulcers. Aspirin is a unique nonselective COX-inhibitor because in very low doses it binds to the COX-1 enzyme of platelets and irreversibly inactivates it, making those platelets less sticky for their There are many nonselective COX inhibitors such as ASPIRIN, IBUPROFEN, DICLOFENAC, PIROXICAM, naproxen, and others. Selective COX-2 inhibitors belong to a new class of NSAIDs that was specifically developed to be more selective for the COX-2 enzyme and thus have anti-inflammatory effects but not affect platelets or cause peptic ulcers. It includes celecoxib, rofecoxib, valdecoxib, and several drugs that are close to being marketed.
The imaging appearance of ulcers varies. Originally described in relation to its angiographic appearance, the ulcer seen in profile (Fig. 30.3) resembles the gastric ulcer as seen on classic barium studies an outpouching of the aortic lumen with thick, overhanging edges. On CT, MRI, or transesophageal echocardiography, the ulcer appears as a nipplelike projection of the aortic lumen communicating with an intramural cavity. When intramural hemorrhage accompanies the ulcer, the aortic wall is thickened. On cross-sectional studies, the