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BACKGROUND: Biliary obstruction with its wide range of potential causes is a common disorder in gastroenterology. Infections of the biliary tract with Candida and other fungal species leading to obstructive jaundice have increasingly been recognized in the last few years. Besides a few case reports, there are few data in the literature giving us an idea how to diagnose and treat these patients. METHODS: We report on a series of seven patients suffering from biliary tract candidiasis who were diagnosed and treated at our institution. Predisposition factors, reliability of various diagnostic modalities, and treatment options based on our own experience are presented and discussed. RESULTS: Besides the general diagnostic modalities such as laboratory findings or ultrasonography, we often observed mycelia in the bile duct system endoscopically. Typical morphological changes in peripheral bile ducts could be detected during endoscopic retrograde cholangiopancreatography (ERCP). Aspiration of bile and subsequent microbiological analysis in combination with ERCP findings revealed diagnosis of bile duct candidiasis in all cases. Treatment included both antiinfectious drugs and endoscopic therapy such as bile duct drainage, lavage, or debridement. With respect to fungal eradication, therapy was successful in 71% of cases as proven by microbiological analysis of bile aspirates. Since many of these patients suffer not only from biliary mycosis but also from disease necessitating immunosuppression, the prognosis was poor in some cases. CONCLUSION: Biliary tract candidiasis because of immunosuppression is an increasingly recognized disease and remains a major clinical challenge. Besides laboratory analysis and ultrasonography, diagnostic modalities should include aspiration of bile during ERCP and microbiological analysis. Antiinfectious drug treatment as the main therapeutic column for biliary candidiasis should be complemented by endoscopic intervention.

The discrepancy between high rates of sensitivity, specificity, and accuracy for intraductal ultrasonography (IDUS) in extrahepatic bile duct carcinoma and the failure to depict different wall layers as defined by the TNM classification have not yet been elucidated sufficiently.In a prospective study, endosonographic images were correlated with histomorphology including immunohistochemistry. Using IDUS, we examined fresh resection specimens of patients who had undergone pancreato-duodenectomy. For histological analysis, the formalin-fixed and paraffin-embedded specimens were stained by hematoxylin-eosin, elastica-van-Gieson, and immunohistochemically by smooth muscle-actin. To confirm our hypothesis, further cases from the archives were analyzed histopathologically and immunohistochemically.The various wall layers of the extrahepatic bile duct as described by the International Union Against Cancer are neither histomorphologically nor immunohistochemically consistently demonstrable. Especially, a clear differentiation between tumor invasion beyond the wall of the bile duct (T2) and invasion of the pancreas (T3) by histopathological means is often not possible. Endosonographic images using high-resolution miniprobes similarly confirm the difficulty in imaging various layers in the bile duct wall.Most adaptations made by the sixth edition of the TNM classification accommodate to the endosonographic and most of the histopathological findings as demonstrated in our study. In contrast to the new edition, however, our findings suggest to combine T2- and T3-staged tumors into one single class leading to clarification, and improved reproducibility of histopathological staging.

A variety of imaging techniques are available to diagnose bile duct strictures; the most effective imaging technique, however, has not been established yet. In the present study, we compared the impact of endoscopic retrograde cholangiopancreatography (ERCP), intraductal ultrasonography (IDUS), and magnetic resonance cholangiopancreatography (MRCP) with regard to diagnosing bile duct strictures.We prospectively examined 33 patients with jaundice due to bile duct strictures by ERCP plus IDUS and MRCP. The objectives were to assess diagnostic quality of imaging, complete presentation of the bile duct, and differentiation of malignant from benign lesions. Surgical and histopathological correlations, which were used as the gold standard, were available in all cases since all included patients underwent laparotomy.Diagnostic image quality for ERCP was 88% and 76% for MRCP (p0.05). Comparing ERCP and MRCP, complete presentation of the biliary tract was achieved in 94% and 82%, respectively (p0.05). ERCP and MRCP allowed correct differentiation of malignant from benign lesions in 76% and 58% (p= 0.057), respectively. By supplementing ERCP with IDUS, the accuracy of correct differentiation of malignant from benign lesions increased significantly to 88% (p= 0.0047).Comparing ERCP with MRCP, we found adequate presentation of bile duct strictures in high imaging quality for both techniques. ERCP supplemented by IDUS gives more reliable and precise information about differentiation of malignant and benign lesions than MRCP alone without additional imaging sequences.

Hepatitis C virus (HCV) infection is a major cause of liver disease characterized by inflammation, cell damage, and fibrotic reactions of hepatocytes. Apoptosis has been implicated in the pathogenesis, although it is unclear whether proteases of the caspase family as the central executioners of apoptosis are involved and how caspase activation contributes to liver injury. In the present study, we measured the activation of effector caspases in liver biopsy specimens of patients with chronic HCV infection. The activation of caspase-3, caspase-7, and cleavage of poly(ADP-ribose)polymerase (PARP), a specific caspase substrate, were measured by immunohistochemistry and Western blot analysis by using antibodies that selectively detect the active truncated, but not the inactive precursor forms of the caspases and PARP. We found that caspase activation was considerably elevated in liver lobules of HCV patients in comparison to normal controls. Interestingly, the immunoreactive cells did yet not reveal an overt apoptotic morphology. The extent of caspase activation correlated significantly with the disease grade, i.e., necroinflammatory activity. In contrast, no correlation was observed with other surrogate markers such as serum transaminases and viral load. In biopsy specimens with low activity (grade 0) 7.7% of the hepatocytes revealed caspase-3 activation, whereas 20.9% of the cells stained positively in grade 3. Thus, our results suggest that caspase activation is involved in HCV-associated liver injury. Moreover, measurement of caspase activity may represent a reliable marker for the early detection of liver damage, which may open up new diagnostic and therapeutic strategies in HCV infection.

Patients with extensive, long-standing ulcerative colitis (UC) have an increased risk for developing colorectal cancer. In this study, we wanted to establish a method for retrieving cytological material after segmental colonic lavage for further cytopathological investigations and for performing DNA image cytometry.Ten patients with long-standing and extensive ulcerative colitis and 10 patients without macroscopic abnormalities were investigated. After segmental colonic lavage during routine colonoscopy a three-layer (1.146, 1.075, and 1.046 g/ml, respectively) density gradient centrifugation of the retrieved colonic fluid was performed for isolation and purification of the epithelial cells. For identification of the epithelial cells flow cytometry with monoclonal antibody against cytokeratin and counterstaining with propidium iodine was performed. The smears obtained were stained for routine cytopathological interpretation and for DNA image cytometry.In eight of 10 UC patients and in nine of 10 control group patients adequate cytological material could be obtained. The band on top of the density gradient at 1.046 g/ml could be identified as the epithelial cells. Atypical cells were found in smears of three UC patients. In these patients and in one additional patient aneuploid stemlines could be detected. In smears of control group patients neither atypical cells nor aneuploidy were present.Isolation and purification of epithelial cells after segmental colonic lavage by using density gradient centrifugation was performed. This cytological material is adequate for cytopathological interpretation and for DNA image cytometry. Information about atypical cells and DNA aneuploidy as an additional marker of malignant transformation in UC patients was obtained. The combination of cytological examination and DNA image cytometry might improve the detection of UC patients with high risk for colorectal cancer.

Objective: Cholecystokinin (CCK) is able to protect gastric mucosa against acute injury in experimental animals but little is known about the role of this hormone in maintaining mucosal integrity in humans. This double-blind, placebo controlled study was performed in 16 healthy volunteers. It describes the effects of CCK-8 infused intravenously (i.v.) at physiological doses and endogenous CCK released by intraduodenal (i.d.) oleate on gastric mucosal damage, as brought about by ethanol without or with pretreatment with loxiglumide, a selective CCK-A receptor antagonist. Methods: CCK-8 was infused i.v. 30 min before and throughout the study or i.d. oleate was instilled through a separate duodenal tube. Thirty minutes after the start of i.v. infusion of CCK or i.d. oleate instillation, 100 ml of 50% ethanol spray was applied to the gastric mucosa using an endoscope. Gastroscopy was performed and mucosal lesions were quantified using modified Lanza score. Gastric biopsies were taken from oxyntic mucosa for histological evaluation and gastric content was aspirated for radioimmunoassay of somatostatin. Results: In placebo-treated subjects ethanol caused endoscopic damage, with an average score of 2.8 ± 0.2. Histologically, a widespread disruption of surface epithelium and deep hemorrhagic necrotic lesions were observed. Pretreatment with CCK or i.d. oleate markedly reduced the endoscopic lesion score to 0.7 ± 0.1 and 0.3 ± 0.1, respectively, and in both cases this reduction was accompanied by a significant rise in plasma CCK. Histologically, surface epithelium was still disrupted but deep necrotic lesions were absent. Gastric content collected before and after CCK or oleate showed a several-fold increase of luminally released somatostatin. Conclusions: Pretreatment with loxiglumide abolished the protective effects of i.v. CCK-8 and i.d. oleate on mucosal lesions induced by ethanol and prevented the rise in intragastric somatostatin, but failed to affect the increments in plasma CCK. Endogenous CCK plays a physiological role in the maintenance of mucosal integrity. This occurs through activation of CCK-A receptors and is associated with an increased gastric luminal release of somatostatin.

This study was designed to determine the involvement of cholecystokinin (CCK) in the control of gastric acid secretion in men using loxiglumide, a specific CCK-receptor antagonist. Two groups of healthy subjects (A and B) were used: group A for studies of postprandial gastric secretion and group B for studies with exogenous gastric secretagogues. The cephalic phase activated by modified sham feeding (MSF) in group A subjects increased gastric acid secretion to about 36% of pentagastrin maximum, but treatment with loxiglumide in a standard dose (20 mumol/kg i.v. loading dose plus infusion of 20 mumol/kg/h afterwards) failed to affect this secretion. A 5% peptone meal instilled i.g. (to mimic the gastrointestinal phase) greatly enhanced gastric acid secretion and plasma gastrin concentration, but the addition of loxiglumide in a standard dose resulted in a further increase in both gastric acid and plasma gastrin responses to the peptone meal. Plasma somatostatin response to the peptone meal was significantly reduced by loxiglumide. Infusion of cerulein in gradually increasing doses (15-120 pmol/kg/h) and gastrin-releasing peptide (GRP) (25-200 pmol/kg/h) resulted in dose-dependent stimulation of gastric acid secretion, reaching about 35 and 25% of the maximum attained with pentagastrin. When loxiglumide was added the acid responses to cerulein and GRP were further increased by two- to threefold, attaining a peak similar to the pentagastrin maximum. Administration of loxiglumide resulted in a significant increase in plasma gastrin response to GRP, whereas plasma somatostatin was not significantly altered by loxiglumide.(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND/AIMS Ampulla of Vater tumors represent a rare tumor entity and bear a malignant potential. This study at our tertiary referral center aimed at evaluating the feasibility of endoscopic snare papillectomy and long-term endoscopic surveillance in comparison to results of a meta-analysis of comparative trials. METHODOLOGY Retrospective study in comparison to results of a meta-analysis. Twenty-one patients (mean age 60.2±12.8 years) with ampullary adenoma were included. All patients had undergone ERCP with endoscopic forceps biopsies prior to endoscopic snare papillectomy. Statistical analysis was applied including descriptive analysis of symptoms, therapy and complications. RESULTS ESP was technically successful in all 21 patients. Histopathology showed 18 adenomas and 3 focal adenocarcinomas which were referred to surgery for modified Whipple's procedure. Follow-up was available in all patients with a mean follow-up of 64 months. Adenoma recurrence occurred in three patients with a mean recurrence time of 25 months (range, 4-66 months). One patient had residual adenoma growth. CONCLUSIONS In the majority of cases ampullary adenomas can be treated endoscopically. Forceps biopsies alone are not reliable enough in detecting malignancy. All patients with ampullary tumor should therefore undergo ESP. Due to the recurrence rate of 16% patients should have close follow-up.

Abnormal activation of transcription factor NF-κB involved in steroid resistance in chronic inflammatory bowel disease