Inhibition of sphincter of Oddi function by the nitric oxide carrier S-nitroso-N-acetylcysteine in rabbits and humans.

Nitric oxide (NO) is an inhibitor of gastrointestinal smooth muscle. Model systems of the gut predict the NO will complex with biological thiol (SH) groups, yielding S-nitrosothiols (RS-NO), which may limit the propensity to form mutagenic nitrosamines. The inhibitory effects of NO and its biologically relevant adducts on sphincter of Oddi (SO) motility have been inferred from animal studies; however, their importance in regulating human SO is not known. The objectives of this study were to (a) provide histologic confirmation of nitric oxide synthase (NOS) in human SO; (b) characterize the pharmacology of S-nitroso-N-acetylcysteine (SNAC), an exemplary S-nitrosothiol, on SO motility in a rabbit model; and (c) study the effects of topical SNAC on SO motility in humans. Immunocytochemical and histochemical identification of NOS was performed in human SO. The pharmacologic response of SNAC was defined in isolated rabbit SO using a standard bioassay. Topical SNAC was then applied to the duodenal papilla in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and biliary manometry. NOS was localized to nerve fibers and bundles of the SO in rabbits and humans. SNAC inhibited spontaneous motility (frequency and amplitude) as well as acetylcholine-induced elevations in SO basal pressure in the rabbit model. In patients undergoing ERCP and biliary manometry, topical SNAC inhibited SO contraction freqency, basal pressure, and duodenal motility. NOS is localized to neural elements in human SO, implicating a role for NO in regulating SO function. Supporting this concept, SNAC is an inhibitor of SO and duodenal motility when applied topically to humans during ERCP. Our data suggest a novel clinical approach using local NO donors to control gastrointestinal motility and regulate sphincteric function.

Endoscopic pH monitoring for patients with suspected or refractory gastroesophageal reflux disease.

BACKGROUND: Wireless pH studies can offer prolonged pH monitoring, which may potentially facilitate the diagnosis and management of patients with gastroesophageal reflux disease (GERD). The aim of the present study was to evaluate the detection rate of abnormal esophageal acid exposure using prolonged pH monitoring in patients with suspected or refractory GERD symptoms. METHODS: Patients undergoing prolonged ambulatory pH studies for the evaluation of GERD-related symptoms were assessed. Patients with a known diagnosis of GERD were tested on medical therapy, while patients with suspected GERD were tested off therapy. The wireless pH capsules were placed during upper endoscopy 6 cm above the squamocolumnar junction. RESULTS: One hundred ninety-one patients underwent a total of 198 pH studies. Fifty ambulatory pH studies (25%) were excluded from the analysis: 27 patients (14%) had insufficient data capture (less than 18 h on at least one day of monitoring), 15 patients had premature capsule release (7%), seven were repeat studies (3.5%) and one had intolerable pain requiring capsule removal (0.5%). There were 115 patients undergoing pH studies who were off medication, and 33 patients were on therapy. For the two groups of patients, results were as follows: 32 (28%) and 22 (67%) patients with normal studies on both days; 58 (50%) and five (15%) patients with abnormal studies on both days; 18 (16%) and three (9%) patients with abnormal studies on day 1 only; and seven (6%) and three (9%) patients with abnormal studies on day 2 only, respectively. CONCLUSIONS: Prolonged 48 h pH monitoring can detect more abnormal esophageal acid exposure but is associated with a significant rate of incomplete studies.

The role of clinical and biochemical criteria and endoscopic retrograde cholangiopancreatography in the urgent diagnosis of common bile duct stones in acute pancreatitis.

The role of clinical and biochemical criteria in predicting common bile duct (CBD) stones was analyzed in 76 patients with acute pancreatitis undergoing endoscopic retrograde cholangiopancreatography (ERCP) during the same hospital admission. Forty patients had ERCP within 72 hours; cholangiography was successful in 92%. Fifty patients had biliary pancreatitis; 25 patients had CBD stones and all were successfully removed by endoscopic sphincterotomy (ES). Twenty-six patients had nonbiliary pancreatitis. Two patients had complications from ERCP and/or ES; two patients died (no CBD stones) but ERCP was noncontributory. Significant differences were found between the biliary and nonbiliary disease groups with respect to age, and bilirubin. gamma-glutamyl transpeptidase, alkaline phosphatase, alanine transaminase, and amylase levels. The first four factors also discriminated between those patients with and without CBD stones. Logistic discriminant functions were estimated providing probabilities for the presence of CBD stones for each patient but were too cumbersome for clinical use. A simple scoring system was devised on the basis of cut-off levels: bilirubin greater than or equal to 40 mumol/L, gamma-glutamyl transpeptidase greater than or equal to 250 IU/L, alkaline phosphatase greater than or equal to 225 IU/L, and age greater than or equal to 70 years, indicating CBD stones. Bilirubin alone had a sensitivity and specificity of 80%; the specificity increased to 93% with all four factors. These results suggest that clinical and biochemical criteria and ERCP and/or ES may have important roles in the management of patients with suspected biliary pancreatitis.

Routine cholangiography is not warranted during laparoscopic cholecystectomy.

The role of intraoperative cholangiography during laparoscopic cholecystectomy was prospectively evaluated in 514 patients undergoing laparoscopic cholecystectomy. Before surgery, all patients were assigned to one of three groups depending on the likelihood of their having common bile duct stones. Stratification was based on objective historical, laboratory, or radiologic criteria. In 453 patients deemed unlikely to have stones, laparoscopic cholecystectomy was performed without cholangiography. Of these patients, four had retained stones (0.9%). In 25 patients likely to have stones, preoperative endoscopic retrograde cholangiopancreatography identified stones in six patients (24%). In 36 patients whose likelihood of having stones was deemed indeterminate, intraoperative cholangiography was performed at laparoscopic cholecystectomy. A common bile duct stone was identified in one patient (2.8%). One common bile duct injury occurred in the group deemed unlikely to have stones, and this injury would not have been prevented by intraoperative cholangiography. We conclude that preoperative assessment will identify common bile duct stones and that routine cholangiography is not warranted. Meticulous dissection of the cystic duct at its origin at the infundibulum will prevent common bile duct injury.

A prospective study of ERCP and endoscopic sphincterotomy in the diagnosis and treatment of gallstone acute pancreatitis. A rational and safe approach to management.

From a consecutive series of 112 patients with acute pancreatitis, 70 patients with suspected gallstones were randomized to urgent endoscopic retrograde cholangiopancreatography (ERCP) (less than 72 hours) and endoscopic sphincterotomy (ES) if choledochal stones were present (n = 35), or to conventional treatment (n = 35). Endoscopic retrograde cholangiopancreatography, successful in 89% of cases, indicated choledochal stones in 11 patients, all of whom underwent successful stone retrieval by ES. Later during hospital admission, ERCP was performed in 13 more patients and choledochal calculi were extracted from two patients by ES. No complications were attributable to ERCP or ES. Two patients died of biliary pancreatitis; both had been conventionally treated and may have benefited from urgent ERCP/ES. Our experience, which extends to another 24 patients with ERCP and ten with ES during acute pancreatitis, indicates that these are safe techniques and deserve wider consideration in the management of acute pancreatitis.

Urinary trypsinogen activation peptides (TAP) are not increased in mild ERCP-induced pancreatitis.

Acute pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) occurs in 3-18% of patients undergoing either diagnostic or therapeutic ERCP. We prospectively measured urinary trypsinogen activation peptides (TAP) by an automated anti-TAP enzyme-linked immunoassay among 107 patients 4 h after ERCP to determine whether this measurement helps in the early diagnosis of ERCP-induced pancreatitis. Pancreatitis was documented in 10 of 107 patients (9.3%). All episodes were graded as mild. Urinary TAP was not significantly increased. We conclude that measurement of urinary TAP 4 h after ERCP is not helpful in documenting mild ERCP-induced acute pancreatitis.

Role of endoscopy in gallstone pancreatitis.

Early identification of those patients presenting with acute pancreatitis due to gallstone disease is important since emergency intervention may prevent the development of local and systemic complications. Urgent biliary surgery carries unacceptably high morbidity and mortality rates, but endoscopic retrograde cholangiopancreatography in experienced centers appears to be safe and is the optimal method for the diagnosis of bile duct stones. Two randomized controlled prospective trials have shown an advantage for endoscopic sphincterotomy and bile duct clearance compared with supportive therapy when performed within 24 to 72 hours of admission in those patients whose symptoms are considered severe according to prognostic scoring systems.

Effects of sphincteroplasty and endoscopic sphincterotomy on the bacteriologic characteristics of the common bile duct.

Forty-five patients with sphincter of Oddi stenosis had specimens of common bile duct cultured during ERCP before either sphincteroplasty or endoscopic sphincterotomy. All had sterile bile before sphincter ablation. Bile was recultured 6 to 36 months later during endoscopy at which time 70 percent of the sphincterotomy and 76 percent of the sphincteroplasty patients had bile colonized principally by enteric organisms. Growth was heavy to moderate in most of the patients and contained few nasopharyngeal organisms. Despite bactobilia, no patient had symptomatic cholangitis, presumably due to excellent drainage of bile. The most likely source of the bactobilia is from direct extension of duodenal organisms into the common bile duct.

Importance of common bile duct stricture associated with chronic pancreatitis. Diagnosis by endoscopic retrograde cholangiopancreatography.

Twenty-one patients with common bile duct strictures associated with chronic pancreatitis are described in whom ERCP was the principal diagnostic method used. In 5 of the 11 patients who had had previous pancreatic or biliary surgery, a common bile duct stricture was overlooked. Nine patients had one or more attacks of cholangitis which were severe in seven and caused death in one. Endoscopically aspirated bile cultures showed heavy gram-negative infection in four patients with previous cholangitis. Two patients developed stones above the strictures, and in one this led to obstruction of a previous cholecystjejunostomy. Although strictures may be discovered at an asymptomatic stage, there should be careful follow-up to detect the appearance of any symptoms or objective signs of stricture progression, when surgery should be offered without delay. Direct biliary-enteric anastomosis is the procedure of choice when possible to relieve symptoms and prevent the potentially life-threatening complications of cholangitis and septicemia.

Sphincterotomy techniques and risks.

Endoscopic sphincterotomy has revolutionized the approach to numerous biliary and pancreatic diseases. The indications, technique, and complications of endoscopic sphincterotomy are covered in detail in this article.

Endoscopic management of acute gallstone pancreatitis.

Urgent management of acute biliary pancreatitis has increasingly included early endoscopic intervention. Endoscopic intervention allows effective removal of the offending stone(s) and reestablishment of biliary drainage. Four randomized controlled trials involving more than 800 patients in Western and Asian countries have been completed. This article summarizes the findings of these studies and proposes a preferred approach to the management of acute biliary pancreatitis.

Mucin-secreting tumors of the pancreas.

Mucinous pancreatic neoplasms present diagnostic and therapeutic challenges. These tumors behave in an indolent nature, with frequent overlap of symptoms and radiographic appearance with other forms of pancreatic cysts, pseudocysts, and malignancy. Some authors propose that all mucin-producing tumors of the pancreas are variants of the same basic entity and have subclassified them on the basis of their predominant location within the pancreas. These disorders must be considered in the evaluation of chronic abdominal pain, particularly in the presence of a cystic pancreatic lesion or when associated with idiopathic chronic or acute recurrent pancreatitis. The clinicopathologic features of IMHN overlap to a great extent with classic mucinous cystic neoplasms but are different significantly enough to be distinct clinical entities. These tumors originate from the pancreatic duct epithelium, produce mucin, demonstrate a papillary growth pattern, and are considered premalignant or frankly malignant at the time of diagnosis. Both lesions biologically are much less aggressive than that of pancreatic ductal adenocarcinoma and appear to infiltrate peripancreatic tissue and to metastasize to lymph nodes or other adjacent structures late in the course of disease. Nevertheless, IMHNs are located primarily in the head of the pancreas, commonly affect elderly men, and present clinically with obstructive pancreatitis, often leading to pancreatic insufficiency, whereas mucinous cystic neoplasms are more likely to develop in the pancreatic body or tail, predominate in young women, and present with symptoms referable to tumor compression of adjacent structures. The location of the lesion is the primary differentiating feature because the lining epithelium of the two tumor types is indistinguishable pathologically. In mucinous cystic tumors, the mucus is secreted and retained within the cyst lumen because of the absence of communication between the cyst and the main pancreatic duct. In contrast, mucus produced in MDE flows into the main pancreatic duct, resulting in obstructive pancreatitis and, ultimately, dilatation of the pancreatic duct. Intraductal mucus provides an important clue to the diagnosis of intraductal pancreatic neoplasms and, whenever present, should prompt an aggressive diagnostic evaluation. Both lesions are managed by resectional surgery because the opportunity for cure is high in the absence of metastatic disease.

Expandable metal stents for gastric-outlet, duodenal, and small intestinal obstruction.

The treatment of patients who have malignant gastric-outlet, duodenal and small intestinal obstructions is difficult. The morbidity and mortality of palliative surgery in these patients is significant. It is not uncommon for patients to be treated with supportive therapy only, which unfortunately, neither relieves the severe nausea and vomiting, nor allows adequate food intake. Over the past few years, a number of studies have reported the safety and efficacy of self-expanding metal stents used to palliate malignant upper gastrointestinal obstruction. In this article, the authors focus on the use of self-expanding metal stents to treat malignant gastric-outlet, duodenal, and small intestinal obstructions.

Pathophysiology of the sphincter of Oddi.

Pathophysiology of the sphincter of Oddi--or sphincter of Oddi dysfunction--manifests as either a biliary-type pain syndrome or recurrent pancreatitis. Imaging studies are unreliable, and direct endoscopic manometry is used to diagnose this entity. Milwaukee biliary classification, in addition to manometry, helps guide therapy. Endoscopic sphincterotomy in selected patients achieves permanent relief of symptoms. Endoscopic therapy for recurrent pancreatitis is still experimental.

Endoscopic palliation for unresectable pancreatic carcinoma.

Endoscopic stenting has revolutionized the palliation of malignant biliary obstruction. Individuals with biliary obstruction due to pancreatic malignancy are best managed by a team approach comprising individuals with expertise in oncology, surgery, endoscopy, and radiology. The clinical value of alleviating jaundice and associated symptoms of anorexia, pruritus, and malaise cannot be overestimated. These quality-of-life factors deserve more attention in future studies to define subgroups of patients most likely to derive benefit from the array of treatment options. Further technical improvements are required to solve the most important clinical problem of late stent occlusion. New developments such as expandable metallic stents and refinements in existing equipment and techniques have already resulted in measurable gains and hold great promise for future expansion of their use in malignant gastric outlet obstruction secondary to tumor infiltration of the duodenum. Corresponding advances are being made in the fields of percutaneous transhepatic intervention and hepatobiliary surgery such that further prospective randomized trials are necessary to define optimal therapy.

Factors affecting the diameters of the common bile duct and pancreatic duct using endoscopic retrograde cholangiopancreatography.

Endoscopic retrograde cholangiopancreatography (ERCP) findings in 405 patients were analyzed to compare common bile duct (CBD) and main pancreatic duct (PD) diameters in relation to age, sex, gallbladder stones, CBD stones and acute pancreatitis. There were 129 patients with gallstones uncomplicated by pancreatitis, 131 patients with pancreatitis, and 145 control subjects. Significant correlations were found between CBD and PD diameters, and between these and age. Independently significant determinants of the CBD diameter were age, female, sex, CBD stones and gallbladder stones, as well as PD diameter. Conversely, PD diameter was significantly dependent upon age, CBD diameter, and acute pancreatitis. This study suggests that both CBD and PD dilation occurs in patients with gallstone disease. In view of the different factors which affect CBD and PD diameters (particularly age), important clinical decisions previously recommended on the basis of these duct diameters may need to be qualified.

Gastrointestinal stromal sarcoma--a case report of palliative enteral stenting.

We report a case of metastatic gastrointestinal stromal sarcoma (GISS) in a 33-year-old man who subsequently underwent successful palliative endoscopically-placed enteral stenting for duodenal stenosis secondary to extrinsic compression. Enteral stenting for palliative relief of malignant gastrointestinal obstruction is recommended for its safety, efficacy and cost-effectiveness.

Endoscopic treatment of acute biliary pancreatitis.

The successes of supportive management of patients with severe acute pancreatitis in recent years has evolved from our improved understanding of some of the serious consequences of pancreatic necrosis on other organ systems. When gallstone disease is identified as the cause in such patients, there has been an expectation that biliary intervention will lead to a more rapid resolution of the index attack and prevention of future pancreatitis. There is now convincing evidence, in the setting of severe gallstone-associated pancreatitis using prognostic scoring, that not only is emergency or early elective biliary surgery associated with an unacceptable morbidity and mortality but that appropriate endoscopic therapy is safe and highly effective. In populations where concomitant cholangitis is common, emergency biliary endoscopic management provides optimal therapy for all grades of pancreatitis.

[Esophageal squamous cell papilloma. Report of 3 cases. Diagnostic aspects]. / Papiloma de células escamosas do esôfago. Apresentação de 3 casos. Aspectos diagnósticos.

UNLABELLED: Dysphagia is not always present in patients with esophageal squamous cell papilloma, and it can be an incidental finding during gastrointestinal endoscopy of an asymptomatic patient. PURPOSE: Three cases of squamous cell papilloma of the esophagus and aspects regarding diagnosis and association with human papillomavirus are presented. CASUISTIC: Two cases are male and one female what is consistent with a higher incidence showed in the literature in males. The three patients were submitted to upper gastrointestinal endoscopy: in one case the tumor was unusually large and in all patients it was located in the mid and lower esophagus. Chromoscopy was performed in one case and the lesion was not stained. We were unable to identify human papillomavirus using DNA-hybridization techniques. Our results are similar to those reported in the review of the literature. RESULTS: There is no other case published in the Brazilian literature and this is the first report on the use of chromoscopy. CONCLUSION: We were not able to show an association between esophageal squamous papilloma and human papillomavirus.