Andreas Püspök

Successful management of benign biliary strictures with fully covered self-expanding metal stents.

BACKGROUND & AIMS Fully covered self-expanding metal stents (FCSEMS) are gaining acceptance for the treatment of benign biliary strictures. We performed a large prospective multinational study to study the ability to remove these stents after extended indwell and the frequency and durability of stricture resolution. METHODS In a nonrandomized study at 13 centers in 11 countries, 187 patients with benign biliary strictures received FCSEMS. Removal was scheduled at 10-12 months for patients with chronic pancreatitis or cholecystectomy and at 4-6 months for patients who received liver transplants. The primary outcome measure was removal success, defined as either scheduled endoscopic removal of the stent with no removal-related serious adverse events or spontaneous stent passage without the need for immediate restenting. RESULTS Endoscopic removal of FCSEMS was not performed for 10 patients because of death (from unrelated causes), withdrawal of consent, or switch to palliative treatment. For the remaining 177 patients, removal success was accomplished in 74.6% (95% confidence interval [CI], 67.5%-80.8%). Removal success was more frequent in the chronic pancreatitis group (80.5%) than in the liver transplantation (63.4%) or cholecystectomy (61.1%) groups (P = .017). FCSEMS were removed by endoscopy from all patients in whom this procedure was attempted. Stricture resolution without restenting upon FCSEMS removal occurred in 76.3% of patients (95% CI, 69.3%-82.3%). The rate of resolution was lower in patients with FCSEMS migration (odds ratio, 0.22; 95% CI, 0.11-0.46). Over a median follow-up period of 20.3 months (interquartile range, 12.9-24.3 mo), the rate of stricture recurrence was 14.8% (95% CI, 8.2%-20.9%). Stent- or removal-related serious adverse events, most often cholangitis, occurred in 27.3% of patients. There was no stent- or removal-related mortality. CONCLUSIONS In a large prospective multinational study, removal success of FCSEMS after extended indwell and stricture resolution were achieved for approximately 75% of patients. ClincialTrials.gov number, NCT01014390.

Current concepts in the pathophysiology of hepatic encephalopathy

The mechanisms causing brain dysfunction in liver failure are still unknown. None of the various hypotheses of the pathogenesis of hepatic encephalopathy (HE) are generally accepted. Since brains of patients with HE cannot be studied with appropriate neurochemica1 or neurophysiological methods, data on cerebral function in HE are usually derived from animal studies. It is beyond the scope of this article to discuss each of the animal models in detail. However, it should be emphasized that these models reflect human disease only in certain aspects. Studies in humans concentrate on biochemical changes in body fluids, mostly in the blood. As the liver has a central role in metabolism it is not surprising that many changes will occur in liver failure. Concentrations of substances produced by the liver will decrease and those catabolised by the liver will increase. It is unknown whether such biochemical abnormalities reflect only decreased hepatic function or are also related to the development of HE. The following mechanisms may impair brain function in liver failure:

18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) does not visualize follicular lymphoma of the duodenum.

Abstract18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) has been used as a potential tool for imaging nodal follicular lymphoma (FL) and extranodal spread. As primary intestinal FL is increasingly being recognized, we have performed a study to investigate the usefulness of 18F-FDG-PET for staging of extranodal FL within the gastrointestinal tract. In eight patients with a diagnosis of FL localized in the duodenum (six cases in stage I and one each in stages II and IV, respectively) whole body 18F-FDG-PET scans were performed. Seven patients with duodenal FL were rated WHO grade 1 and one had FL grade 3, while both patients with secondary spread had FL WHO grade 1. All patients were imaged before initiation of therapy. None of the patients with primary duodenal FL showed pathologically elevated 18F-FDG uptake. 18F-FDG-PET findings were not influenced by histological grade or proliferative activity of FL. These findings suggest that 18F-FDG-PET is not useful for clinical assessment of primary duodenal FL.

Plummer-Vinson syndrome associated with celiac disease and complicated by postcricoid carcinoma and carcinoma of the tongue.

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Primary Gastric Mantle Cell Lymphoma in a Patient with Long Standing History of Crohn's Disease

The stomach is the most common site of primary extranodal lymphoma. Virtually all cases are of B-cell lineage, including extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma) and diffuse large B-cell lymphomas. While secondary gastric involvement from nodal mantle cell lymphoma (MCL) or in the course of primary intestinal MCL (lymphomatous polyposis) have been described, primary gastric MCL has not been reported so far. A 74-year-old man with a 14 year-history of Crohns disease was admitted at a general hospital due to epigastric pain refractory to therapy with proton-pump inhibitors. Endoscopy disclosed a large polypoid tumor with an ulcerated surface at the greater curvature of the gastric antrum. Endosonography demonstrated the tumor to be limited to the stomach with only local lymph node involvement. Histology of gastric biopsies revealed a dense atypical lymphoid infiltrate composed of small to medium sized cells with slightly irregular nuclear contours. Immunohistochemichally, the cells were positive for CD20, CD79a, CD43 and cyclin D1, but negative for CD3, CD5 and bcl-6. They stained for IgM and showed lambda-light chain restriction. Fluorescent in situ hybridisation studies showed the presence of the t(11;14) characteristic for MCL. No further evidence of lymphoma was found on extensive clinical staging. Following chemotherapy the patient is disease free at 24 months after diagnosis. This is the first case of a primary localized gastric MCL. The lack of CD5 expression underscores the importance of performing thorough immunohistochemical studies, particularly to exclude MALT lymphoma.

Neuropharmacologic Modulation of Hepatic Encephalopathy: Experimental and Clinical Data

Various neurochemical studies in hepatic encephalopathy (HE) (for review: 1) indicate that alterations of several neurotransmitter systems including the GABAA-benzodiazepine-ergic, glutamatergic, dopaminergic, serotoninergic, noradrenergic and opiatergic neurotransmitter systems may contribute to the pathogenesis of this syndrome, but the precise role of each of these changes remains controversial. Using specific agonists and antagonists of these neurotransmitters the importance of altered neurotransmission in HE can be examined in vivo. Such experiments may improve our understanding of the pathophysiology of HE and can ultimately help to develop better treatments. In this paper the current status of neurobehavioural studies in experimental and in human HE will be reviewed.

Gallengangsprobleme : durch technische Entwicklungen zu verändertem Patientenmanagement

SummaryModern cross sectional imaging methods like CT and MRCP have replaced more invasive methods for the diagnosis of cholangiolithiasis as well as benign and malignant biliary strictures. Only if a histologic or cytologic confirmation of the diagnosis is necessary, is a direct access to the biliary tract either with ERC or PTC justified as a diagnostic procedure. Due to technical advancements in laparoscopic surgery intraoperative bile duct revision has become a standard procedure for patients with choledocholithiasis discovered during cholecystectomy. It has been shown to be equally effective to ERC. In this setting ERC therefore has lost its unique claim for the treatment of bile duct stones, while it remains the treatment of choice in patients with prior cholecystectomy. In contrast ERC, sometimes in combination with PTC, has become the mainstay in the treatment of biliary lesions like leakage and benign strictures. The same is true for the palliation of malignant biliary strictures. Surgery should be reserved for patients in whom minimal invasive methods fail and for the curative treatment of malignant lesions.ZusammenfassungModerne Schnittbildverfahren haben invasivere Methoden, wie die ERC und PTC in der Diagnostik der Choledocholithiasis, sowie von benignen und malignen Strikturen weitgehend abgelöst. Der direkte Zugang zum Gallengang aus diagnostischen Gründen ist lediglich noch für die Gewinnung von Material zur histologischen oder zytologischen Diagnostik notwendig. Seit Einführung der routinemäßigen intraoperativen Cholangiographie bzw. Choledochusrevision im Rahmen der laparoskopischen Cholezystektomie ist neuerlich ein Wechsel in der Behandlungsstrategie der Choledocholithiasis erfolgt. Die ERC hat hier ihren singulären Anspruch als wenig invasives Verfahren zur Therapie der Choledocholithiasis verloren, sofern gleichzeitig die Indikation zur Cholezystektomie besteht; sie ist lediglich für Patienten mit St.p. Cholezystektomie das Therapieverfahren der ersten Wahl geblieben. In der Therapie von Gallengangsläsionen, seien es Leckagen, benigne oder maligne Stenosen, haben sich wenig invasive Verfahren, allen voran die Endoskopie als Therapie der ersten Wahl durchgesetzt. Der Stellenwert der Chirurgie liegt hier in der Behandlung von Therapieversagern sowie in der kurativen Tumorchirurgie.

Gallengangsprobleme – durch technische Entwicklungen zu verändertem Patientenmanagement@@@Influence of technical advancements on the management of biliary tract diseases

SummaryModern cross sectional imaging methods like CT and MRCP have replaced more invasive methods for the diagnosis of cholangiolithiasis as well as benign and malignant biliary strictures. Only if a histologic or cytologic confirmation of the diagnosis is necessary, is a direct access to the biliary tract either with ERC or PTC justified as a diagnostic procedure. Due to technical advancements in laparoscopic surgery intraoperative bile duct revision has become a standard procedure for patients with choledocholithiasis discovered during cholecystectomy. It has been shown to be equally effective to ERC. In this setting ERC therefore has lost its unique claim for the treatment of bile duct stones, while it remains the treatment of choice in patients with prior cholecystectomy. In contrast ERC, sometimes in combination with PTC, has become the mainstay in the treatment of biliary lesions like leakage and benign strictures. The same is true for the palliation of malignant biliary strictures. Surgery should be reserved for patients in whom minimal invasive methods fail and for the curative treatment of malignant lesions.ZusammenfassungModerne Schnittbildverfahren haben invasivere Methoden, wie die ERC und PTC in der Diagnostik der Choledocholithiasis, sowie von benignen und malignen Strikturen weitgehend abgelöst. Der direkte Zugang zum Gallengang aus diagnostischen Gründen ist lediglich noch für die Gewinnung von Material zur histologischen oder zytologischen Diagnostik notwendig. Seit Einführung der routinemäßigen intraoperativen Cholangiographie bzw. Choledochusrevision im Rahmen der laparoskopischen Cholezystektomie ist neuerlich ein Wechsel in der Behandlungsstrategie der Choledocholithiasis erfolgt. Die ERC hat hier ihren singulären Anspruch als wenig invasives Verfahren zur Therapie der Choledocholithiasis verloren, sofern gleichzeitig die Indikation zur Cholezystektomie besteht; sie ist lediglich für Patienten mit St.p. Cholezystektomie das Therapieverfahren der ersten Wahl geblieben. In der Therapie von Gallengangsläsionen, seien es Leckagen, benigne oder maligne Stenosen, haben sich wenig invasive Verfahren, allen voran die Endoskopie als Therapie der ersten Wahl durchgesetzt. Der Stellenwert der Chirurgie liegt hier in der Behandlung von Therapieversagern sowie in der kurativen Tumorchirurgie.

Esophageal epithelium in Crohn's disease: HLA-DR expression: A diagnostic sign of microscopic disease?

We demonstrated that T. cruzi infection is associated with myocardial inducible nitric oxide synthase (iNnS) expression. We therefore examined the T. cruzi-associated distribution and the activity of the NOS isoforms, neuronal NOS (nNOS), endothelial NOS (eNOS) and iNnS in the esophagus, stomach, ileum and colon of CD-1 mice 30 days post-infection with the Brazil strain using immunohistochemistry (IHC). NOS activity was measured by the formation of L[laC]citrnlline from L-[laC]arginine. There were no pathological changes in the gastrointestinal tract 30 days postinfection. nNOS-immunoreactivity was seen in nerve cell bodies in the enteric plexus, and in nerve fibers mainly localized to the smooth muscle, eNOSimmunoreactivity was confined to vascular endothelium. By IHC there were no significant differences in nNOS-and eNOS-immunoreactivities between infected and uninfected mice. In infected mice, iNOS-immunoreactivity was observed in clusters of cells within the submucosa and the circular and longitudinal muscle layers. In the stomach, ileum and colon epithelial cells expressed iNOS-immunoreactivity. No iNOS-immunoreactivity could be observed in the digestive tract in uninfected mice. In all regions of the gastrointestinal tract Ca2+-dependent (nNOS/eNOS) activity was lower in the infected mice than in the controls. However, in infected mice there was an increased Ca2+-independent (iNnS) activity in the esophagus, stomach and colon compared to controls. These data demonstrate that T. cruzi infection is associated with an increased iNnS expression and activity in gastrointestinal epithelium and certain cells in the submucosa and the muscle layers. In addition, a decreased nNOS/eNOS-activity was found. Alterations in the nitric oxide pathway of the gastrointestinal tract may be an early event in this infection and a target for pharmacological intervention.