Performance characteristics of optical coherence tomography in assessment of Barrett's esophagus and esophageal cancer: systematic review.

Optical coherence tomography (OCT) can generate high-resolution images of the esophagus that allows cross-sectional visualization of esophageal wall layers. We conducted a systematic review to assess the utility of OCT for diagnosing of esophageal intestinal metaplasia (IM; Barrett's esophagus BE)), dysplasia, cancer and staging of early esophageal cancer. English language human observational studies and clinical trials published in PubMed and Embase were included if they assessed any of the following: (i) in-vivo features and accuracy of OCT at diagnosing esophageal IM, sub-squamous intestinal metaplasia (SSIM), dysplasia, or cancer, and (ii) accuracy of OCT in staging esophageal cancer. Twenty-one of the 2,068 retrieved citations met inclusion criteria. In the two prospective studies that assessed accuracy of OCT at identifying IM, sensitivity was 81%-97%, and specificity was 57%-92%. In the two prospective studies that assessed accuracy of OCT at identifying dysplasia and early cancer, sensitivity was 68%-83%, and specificity was 75%-82%. Observational studies described significant variability in the ability of OCT to accurately identify SSIM. Two prospective studies that compared the accuracy of OCT at staging early squamous cell carcinoma to histologic resection specimens reported accuracy of >90%. Risk of bias and applicability concerns was rated as low among the prospective studies using the QUADAS-2 questionnaire. OCT may identify intestinal metaplasia and dysplasia, but its accuracy may not meet recommended thresholds to replace 4-quadrant biopsies in clinical practice. OCT may be more accurate than EUS at staging early esophageal cancer, but randomized trials and cost-effective analyses are lacking.

Safety and efficacy of endoscopic spray cryotherapy for esophageal cancer.

Although surgery is traditionally the standard of care for esophageal cancer, esophagectomy carries significant morbidity. Alternative endoscopic therapies are needed for patients who are not candidates for conventional treatment. The objective of this study is to assess the safety, efficacy, and tolerability of spray cryotherapy of esophageal adenocarcinoma. This study includes patients with esophageal adenocarcinoma who had failed or were not candidates for conventional therapy enrolled retrospectively and prospectively in an open-label registry and patients in a retrospective cohort from 11 academic and community practices. Endoscopic spray cryotherapy was performed until biopsy proven local tumor eradication or until treatment was halted due to progression of disease, patient withdrawal or comorbidities. Eighty-eight patients with esophageal adenocarcinoma (median age 76, 80.7% male, mean length 5.1 cm) underwent 359 treatments (mean 4.4 per patient). Tumor stages included 39 with T1a, 25 with T1b, 9 with unspecified T1, and 15 with T2. Eighty-six patients completed treatment with complete response of intraluminal disease in 55.8%, including complete response in 76.3% for T1a, 45.8% for T1b, 66.2% for all T1, and 6.7% for T2. Mean follow-up was 18.4 months. There were no deaths or perforations related to spray cryotherapy. Strictures developed in 12 of 88 patients (13.6%) but were present before spray cryotherapy in 3 of 12. This study suggests that endoscopic spray cryotherapy is a safe, well-tolerated, and effective treatment option for early esophageal adenocarcinoma.

Colorectal cancer. A blueprint for disease control through screening by primary care physicians.

The Virginia Colorectal Cancer Control Project is a statewide effort to reduce morbidity and mortality from colorectal cancer by stimulating the adoption of screening and early detection practices by primary care physicians. The project emphasizes use of the three-day fecal occult blood test, digital rectal examination, and endoscopy. Recruitment strategies included personal contact, newsletters, journal articles, and screening workshops. Of the 33 318 patients screened over 26 months, positive fecal occult blood test reactions were recorded in 3.3% of asymptomatic patients and in 14.8% of symptomatic patients. Polyps were found in 149 and cancer was diagnosed in 94 patients of whom one third were asymptomatic. Eighty percent of the latter had Dukes' A and B lesions, 12% had Dukes' C lesions, and 8% had Dukes' D lesions. In contrast, only 36% of the symptomatic cancers were Dukes' A and B lesions, and 69% were Dukes' C and D lesions. These results suggest that primary care physicians can be effective in the screening and detection of precancerous polyps and early-staged colorectal cancers.

Prevention of acute gastrointestinal complications after severe head injury: a controlled trial of cimetidine prophylaxis.

Cimetidine prophylaxis significantly reduced the risk of gastrointestinal bleeding after severe head injury in this prospective, double-blind clinical trial. Cimetidine effectively reduced both the volume and the acidity of gastric secretions after brain injury without producing adverse side effects. The most common endoscopic finding was superficial, erosive, mucosal lesions in the proximal stomach. Cimetidine prophylaxis was not shown to reduce the incidence of these lesions in this study but did diminish their severity and the likelihood that they would complicate the management of these patients.

Recurrent acute pancreatitis caused by a gastric duplication communicating with an aberrant pancreas.

A 24-year-old female patient who had suffered from recurrent bouts of acute pancreatitis for over 3 years was found on endoscopic retrograde cholangiopancreatography to have an aberrant pancreatic duct that terminated in a cyst. An aberrant lobe of pancreas had been discovered at exploratory laparotomy 3 years previously and was left untreated. Excision of the aberrant lobe of pancreas and accompanying gastric duplication cyst was curative. This case illustrates the importance of obtaining endoscopic retrograde cholangiopancreatography in all young individuals with recurrent pancreatitis to detect this rare, but curable, cause of pancreatitis.

A prospective assessment of the Garren-Edwards Gastric Bubble and bariatric surgery in the treatment of morbid obesity.

Morbid obesity is a serious medical hazard, and effective alternatives to surgery have been unsuccessful. In 1985, the Garren-Edwards Gastric Bubble (GEGB) was offered as an adjunct to dietary and behavioral therapy for weight loss treatment. The safety and efficacy of the GEGB were compared with bariatric surgery, the current standard for the treatment of morbid obesity. Fifty-seven patients received GEGB and 77 underwent bariatric surgery. GEGB patients were divided into two groups: those who attended group therapy and those who did not. This study showed that bariatric surgery was far more effective in reducing excess body weight during a 12-month period compared with the GEGB plus group therapy and the GEGB alone. The morbidity from bariatric surgery was greater than in the GEGB-treated groups, while the cost for uncomplicated cases for a year's treatment was comparable. It is concluded that the GEGB does not offer an effective alternative to bariatric surgery in the treatment of morbid obesity.

Endoscopic ultrasound.

Endoscopic ultrasound is currently an accepted part of the clinical practice of gastroenterology. It is used to evaluate submucosal lesions, thickened gastric folds, and depth of gastrointestinal tumor penetration. As the capabilities of the instruments improve, their role in the practice of gastroenterology widens. This review is designed to update the practicing physicians on this rapidly evolving field, pertaining to instrumentation for endosonography, clinical indications for endosonography, and future directions.

Gallstone pancreatitis: an update.

Gallstone pancreatitis is one of the more prevalent causes of pancreatitis. It accounts for more than two thirds of the cases of acute pancreatitis worldwide and 25 to 45% of the cases in the United States. Furthermore, it is one of the most important treatable causes of pancreatitis. These two important features of the disease make its recognition and proper management critical. Key to recognition and proper management of gallstone pancreatitis is understanding that this disease can exist in three different forms. It can exist as impacted gallstone pancreatitis, as nonimpacted gallstone pancreatitis, or as sludge-related pancreatitis. Each of these forms of the disease will have some unique features relating to their pathogenesis, diagnosis, and treatment. This update focuses on "take-home" features that will allow (1) clinical differentiation between the three forms of the disease and (2) understanding the unique features that relate to their pathogenesis, diagnosis, and management.

Endoscopic ultrasound-guided (neurolytic) celiac plexus block.

Celiac plexus neurolysis is an established technique for relieving pain in cancers of the upper abdomen. This article reviews the novel technique of endoscopic ultrasound (EUS)-guided neurolytic celiac plexus block. This recently described procedure is a therapeutic extension of curvilinear array endosonographic fine needle aspiration. The indications, patient preparation, and technical aspects of the procedure are described in detail. The potential complications are mentioned and the results of the published studies are reviewed. We believe that where the expertise is available, this procedure can be integrated into the diagnostic EUS of patients with inoperable upper abdominal malignancy. As such, this would be the safest and most cost-effective approach for celiac plexus neurolysis in these patients. The role of EUS-guided celiac plexus block in patients with chronic pancreatitis may be emerging and needs further study.

Pharmacological control of gastric acid secretion.

Gastric acid produced by the parietal cells has a significant role in a variety of gastrointestinal diseases, such as duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease. We address acid production by the parietal cell and the pharmacological means to control gastric acid secretion. The physiology of parietal cell acid secretion is reviewed. The role of acid-suppressive therapy with histamine H2 antagonists and omeprazole in duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease is discussed. Pharmacology, side-effect profile, and dosage requirements of the histamine H2 antagonists and omeprazole are outlined.

Nonsteroidal antiinflammatory drug-induced gastroduodenal lesions: prophylaxis and treatment.

Nonsteroidal antiinflammatory drugs (NSAIDs) are one of the most commonly prescribed agents, especially for elderly patients. These drugs frequently produce mucosal petechiae and erosions in the stomach and duodenum, but these conditions are rarely of clinical significance. NSAIDs, however, cause considerable morbidity and mortality due to their ability to cause gastric and duodenal ulcers. NSAID-induced ulcers are most likely to develop in elderly women receiving multiple NSAIDs for prolonged periods. NSAIDs injure gastric and duodenal mucosa by both a topical and a systemic effect. The latter is responsible for the pathogenesis of NSAID-associated ulcers. These ulcers are particularly prone to perforation and hemorrhage. Both complications frequently occur in asymptomatic long-term users of NSAIDs. H2 antagonists prevent NSAID-related duodenal ulcers but are not effective for prevention of gastric ulcers. Misoprostol is the only agent proven to decrease the risk of gastric ulcers in patients receiving NSAIDs. Both H2 antagonists and omeprazole are highly effective for the treatment of established duodenal ulcers in patients receiving NSAIDs. H2 antagonists also heal gastric ulcers in these patients but at slower rates than in patients not receiving NSAIDs. The existing literature is reviewed, and guidelines for prophylaxis against NSAID-induced ulcers and treatment of established ulcers are provided.

Small intestinal motility: normal and abnormal function.

This review outlines the properties and function of intestinal smooth muscle and the mechanisms that underlie contraction and relaxation. Both tonic and phasic (rhythmic) contraction are mediated by an increase in intracellular calcium. Phasic contraction is paced electrically by rhythmic changes in membrane potential (slow waves) which, upon reaching a threshold, lead to opening of membrane calcium channels and the entry of calcium into muscle cells; this inwardly directed calcium current or spike initiates a cascade of events resulting in contraction. Slow waves and spike potentials and, thus, phasic contraction, are influenced by neurotransmitters, hormones, and drugs. In circular muscle, these agents can also increase calcium by releasing it from intracellular stores, thus inducing tonic contraction. Ingestion of food initiates peristaltic propulsive activity which, in its rhythm, is superimposed on spontaneous phasic activity. The peristaltic reflex consists of two successive phases: relation of circular muscle distal to the distending bolus (descending relaxation) and contraction proximal to the bolus (ascending contraction). In-between meals, a different, slower pattern of muscle activity prevails, known as the migrating motor complex, which helps to maintain the lumen of the intestine free of contents. Improved understanding of normal muscle function is beginning to reflect itself in improved management of patients with motility disorders.

Small flat adenoma: important in colon carcinogenesis?

The risk for development of colonic carcinoma increases with increasing size of the polyp. Endoscopists have focused attention on large polyps. Small flat adenomas are sessile polyps that measure less than 1 cm; they are nearly flat, and they have a slight depression in the center. They have a high incidence of cancer in situ. Adenomatous polyps follow the adenoma-carcinoma sequence. Small flat adenomas do not appear to follow this sequence, but they may be precursors of so called de novo colonic carcinoma. The genetics of small flat adenomas are not fully elucidated. Small flat adenomas may not be identified during standard colonoscopy due to the small size of the lesion. Chromoendoscopy may increase the rate of detection.

Interaction of acetylcholine and cholecystokinin with dispersed smooth muscle cells.

Isolated gastric smooth muscle cells were prepared from the stomach of Bufo marinus by successive incubation in collagenase without added trypsin. Contraction was determined by image-splitting micrometry and expressed as the mean percentage decrease in cell length from control. Peak contractile response was attained within 30 s. Dose-response curves constructed from peak responses showed that the maximal responses to CCK-OP (37.2 +/- 3.8%), acetylcholine (35.3 +/- 2.5%), and Ca2+ (42.3 +/- 0.9%) were similar. The D50s for octapeptide of cholecystokinin (CCK-OP) and acetylcholine were around 10(-12) M and 10(-11) M, respectively. The response to a combination of submaximal concentrations of acetylcholine and CCK-OP exceeded the individual responses but did not exceed the maximal response to either agent alone. A low concentration of atropine (5 X 10(-10) M) inhibited specifically the maximal response to acetylcholine. A high concentration of atropine (5 X 10(-8) M) inhibited partially the maximal response to CCK-OP but had no effect on the maximal response to Ca2+. It was concluded that 1) dispersed gastric smooth muscle cells are highly sensitive to stimulation; 2) CCK-OP has a direct (myogenic) contractile effect on gastric smooth muscle; and 3) the effect of CCK-OP and acetylcholine are mediated by separate receptors.

Binding of secretin to plastic surfaces.

Five carboxyl-terminal fragments of secretin ranging in size from 6 to 21 amino acid residues were tested for pancreatic secretory activity in the rat. None of the fragments displayed activity when given alone but each displayed significant activity when given after secretin. This apparent activity was shown to be the result of displacement of secretin bound to the walls of the injection catheter. The activity was abolished by dissolving secretin in 2% bovine serum albumin. The finding emphasizes the ease with which secretin can bind to plastic surfaces and consequently the need to reevaluate previous dose-response studies and the caution required in the design of future studies.

Magnetic resonance cholangiopancreatography: a new technique for evaluating the biliary tract and pancreatic duct.

Magnetic resonance cholangiopancreatography (MRCP) represents a new development in MR technology that provides a noninvasive accurate means of evaluating the biliary tree and pancreatic duct. Recent technical refinements that allow for imaging of the entire biliary tree and pancreatic duct in 18 seconds make this examination easily performed even in critically ill patients. The clinical applications of MRCP are illustrated in a variety of scenarios that include choledocholithiasis, malignant obstruction, incomplete/failed endoscopic retrograde cholangiopancreatographies (ERCPs), postsurgical alterations of the biliary tract and gastrointestinal tract such as biliary-enteric anastomoses, intrahepatic bile duct pathology such as sclerosing cholangitis and AIDS cholangiopathy, chronic pancreatitis, congenital anomalies of the biliary tract and pancreatic duct, and gallbladder pathology.

Mediation of guinea pig gastric secretion in vitro by cyclic nucleotides.

The effect of methacholine, theophylline, and cyclic adenyl and guanyl nucleotides on gastric secretion from antral and proximal duodenal mucosa of the guinea pig was studied. Both 2 mM dibutyryl (db) cAMP and 5 mM theophylline produced significant increases in gastrin secretion, 4.3 +/- 0.7 (P less than 0.001) and 9.3 +/- 2.4 pg mg-1 min-1 (P less than 0.005) respectively, above basal gastrin secretion (1.5 +/- 0.4 pg mg-1 min-1). The combined effect of the two agents was additive (14.5 +/- 3.6 pg mg-1 min-1). Db cGMP (2 mM) had no effect on gastrin secretion. Methacholine produced a dose-related increase in gastrin secretion which at maximum equaled the combined effect of theophylline and db cAMP. The results suggest that gastrin secretion is mediated in part by intracellular cAMP but do not exclude a cooperative involvement of cGMP.

Stimulatory (H1) and inhibitory (H2) histamine receptors in gallbladder muscle.

The nature of histamine receptors in gallbladder muscle and examined using specific histamine-receptor agonists and antagonists. The H2-receptor antagonist, metiamide, augmented the contractile response to histamine indicating that gallbladder muscle possessed stimulatory H1 receptors and inhibitory H2 receptors. The independent inhibitory character of H2 receptors was confirmed by (1) induction of relaxation with histamine after H1-receptor blockade and the suppression of this relaxation with metiamide, and (2) induction of relaxation with a specific H2-receptor agonist, 4-methyl histamine and the suppression of this relaxation with metiamide. Further, blockade of H2 but not of H1 receptors augmented the response to the octapeptide of cholecystokinin. The nature of this effect was such that the apparent affinity of the octapeptide for its own receptor was increased. The finding raised the possibility that in their native unoccupied state, H2 receptors may modify the response to hormonal agents.

Gastric and esophageal dysfunction after ingestion of acid.

Esophageal and gastric function was measured in a patient who swallowed a household acid solution. Dysphagia, transient ulceration of the esophagus with luminal narrowing, and complete loss of peristalsis without loss of lower esophageal sphincter function were noted. Gastric dysfunction appeared 2 weeks after ingestion with complete obstruction, necessitating antral resection. The proximal stomach was relatively spared.