[Consensus on basic principles of team work between gastroenterologists and visceral surgeons].
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Biomedical subjects
Publications and source records attributed to U R Fölsch.
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We here report the successful but unusual course of colonic tattooing in a patient with a carcinoma in situ in a polyp. A 70-year-old woman was admitted for persistent diarrhea, occult fecal blood, and anemia. During colonoscopy, a pedunculated large polyp in the sigmoid colon occluding the lumen was removed successfully. Histopathological examination revealed a carcinoma in situ with a resection of the peduncle in sano. At the second sigmoidoscopy, the polypectomy site was marked with India ink to facilitate the recovery of the polypectomy site in follow-up endoscopies. Three months later, the India ink had spread in the submucosal layer and a segment measuring 15 cm was colored dark blue. At the original polypectomy site, an uncolored flat mucosal proliferation was found above the dark colonic wall. After mucosectomy, the tissue was classified as hyperplastic. Six weeks later, a second control sigmoidoscopy did not show any suspicious mucosal alterations.
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BACKGROUND: Problems with intubation of the ampulla Vateri during diagnostic and therapeutic endoscopic maneuvers are a well-known feature. The ampulla Vateri was analyzed three-dimensionally to determine whether these difficulties have a structural background. METHODS: Thirty-five human greater duodenal papillae were examined by light and scanning electron microscopy as well as immunohistochemically. RESULTS: Histologically, highly vascularized finger-like mucosal folds project far into the lumen of the ampulla Vateri. The excretory ducts of seromucous glands containing many lysozyme-secreting Paneth cells open close to the base of the mucosal folds. Scanning electron microscopy revealed large mucosal folds inside the ampulla that continued into the pancreatic and bile duct, comparable to valves arranged in a row. CONCLUSIONS: Mucosal folds form pocket-like valves in the lumen of the ampulla Vateri. They allow a unidirectional flow of secretions into the duodenum and prevent reflux from the duodenum into the ampulla Vateri. Subepithelial mucous gland secretions functionally clean the valvular crypts and protect the epithelium. The arrangement of pocket-like mucosal folds may explain endoscopic difficulties experienced when attempting to penetrate the papilla of Vater during endoscopic retrograde cholangiopancreaticographic procedures.
Infliximab (anti-TNF-alpha monoclonal antibody) induces remission in 30-40% of Crohn's disease patients. Treatment response is a stable trait. Two cohorts from independent, prospective clinical trials of infliximab in Crohn's disease were studied. Hypotheses were generated in an exploratory cohort (n = 90) and then tested in a confirmatory cohort (n = 444), using a statistical design, which is stable against type 1 and type 2 errors. In the exploratory cohort, the mutant 196Arg allele of TNFR-II (exon 6 polymorphism) and a novel silent polymorphism in exon 2 of TNFR-II were associated with lack of response to infliximab (83.3% in homozygote mutant 196 Arg patients vs 36.9% in heterozygotes and wild-type homozygotes (P = 0.036) and 85.7% in homozygote mutant exon 2 patients vs 36.1% (P = 0.01), respectively). None of the homozygote mutant individuals (0/6) achieved clinical remission, whereas the remission rate was 35.7% (30/84) in wild-type homozygotes and heterozygotes. In the large second cohort, the observed genotype-phenotype associations were not replicated. Other polymorphisms (TNF-alpha promoter -238, -308, -376, -857, -1031, TNF-R-I -609, +36 (exon 1), TNF-R-II 1663, 1690 (3'-UTR)) were not associated with treatment response in both cohorts (P > 0.5). None of the polymorphisms was associated with refractory Crohn's disease itself when compared to healthy controls. In a two-cohort study, a series of polymorphisms in the TNF, the TNF-R-I and in the TNF-R-II genes could be thoroughly excluded as pharmacogenetic markers for a treatment response to infliximab and as etiologic factors for Crohn's disease, respectively. The discrepancy between the two cohorts observed for the TNF-R-II exon 6 and exon 2 polymorphism may point to a weak effect on treatment response but also serves to illustrate the need for a sequential exploratory/confirmatory design in pharmacogenetic studies.
Intestinal endometriosis is the most frequent extragenital manifestation of this disease. Sometimes patients even present with acute bowel obstruction. We report on a 46-year-old woman complaining about recurrent sanguineous and mucous diarrhea and spasms for several years. Colonoscopy showed a stenosis in the sigmoid colon without macroscopically visible alterations of the mucosa. Computertomography, ultrasound and barium contrast enema did not provide us with further information about the origin of the stenosis. Biopsies out of the mucosa at the stenosis showed typical endometriosis tissue. After starting a conservative therapy with GnRH-agonist gosereline the patient became completely free of symptoms. The coincidence of endometriosis and M. Crohn has to be taken into consideration. Therapy planning should include a close co-operation with gynaecologists and surgeons to transfer the patient to surgical intervention when needed.
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In portal vein thrombosis, various hypercoagulable conditions and inherited or acquired thrombophilias have already been described as predisposing factors. In a 33-year-old man admitted to a hospital with upper abdominal pain, a partial portal vein and upper mesenteric vein thrombosis, respectively, and a complete splenic vein thrombosis were diagnosed. Further diagnostic procedures showed no evidence for local precipitating factors or any underlying infectious, paraneoplastic or inflammatory disease. Thrombophilia screening demonstrated elevated factor VIII levels (206 %) and von Willebrand factor levels (> 440 %). An acute-phase reaction was excluded. Oral anticoagulant therapy with phenprocoumon was started. Factor VIII and von Willebrand factor were reproducibly elevated to high activity levels over a period of 12 months in absence of acute or chronic inflammatory reaction. Increased levels of factor VIII and von Willebrand factor may play a pathogenetic role in the development of portal, splenic, and mesenteric thrombosis.
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BACKGROUND: Increased expression of proinflammatory cytokines, including tumour necrosis factor alpha, interleukin 6, and interferon gamma, as well as activation of proinflammatory signalling molecules such as nuclear factor kappa B, is characteristic of inflammatory bowel disease (IBD). AIMS: To investigate expression and activation of signal transducer and activator of transcription (STAT) 1 in patients with IBD. PATIENTS: Patients with active IBD (n=42), disease specificity controls (n=8), and normal controls (n=12) were investigated. METHODS: Expression and activation of STAT1 were assessed by western blotting and electrophoretic mobility shift assays in extracts of endoscopic colonic biopsies. Cellular localisation was determined by immunohistochemistry. RESULTS: Western blots and immunohistochemical staining revealed an increase in STAT1 expression and activation in mucosal samples from ulcerative colitis and to a lesser extend in Crohn's disease patients. High levels of suppressor of cytokine signalling (SOCS)-3 expression, an inhibitor of STAT activation, were observed in Crohn's disease patients and normal controls in western blot experiments whereas no differences were observed for SOCS-1 expression. Phosphorylated (p) STAT1 was mainly detected in monocytic cells and neutrophils in the inflamed mucosa. Induction of remission by systemic glucocorticoids led to a decrease in levels of pSTAT1. In vitro studies indicated a direct effect of steroid treatment on STAT1 activation. CONCLUSIONS: Expression and activation of STAT1 are predominantly heightened in ulcerative colitis and may therefore play an important role in the pathophysiology of colonic inflammation.
BACKGROUND: Hepatitis C virus (HCV) infection is a significant problem in the management of haemodialysis patients. A high prevalence of HCV infection in haemodialysis patients has been reported. Risk factors such as the number of blood transfusions or duration on haemodialysis have been identified. AIM: To determine the prevalence of HCV by antibody testing and HCV-RNA determination by polymerase chain reaction (PCR) in haemodialysis patients. Furthermore, liver function tests were performed and epidemiological data were obtained to determine risk factors for HCV in this cohort of patients. RESULTS: A total of 2796 patients from 43 dialysis centres were enrolled. The overall prevalence of HCV (HCV antibody and/or HCV-RNA positivity) was 7.0% (195 patients). Antibody positivity occurred in 171 patients (6.1%). Viraemia was detectable in 111 patients (4.0%). Twenty four of 111 HCV RNA positive patients (21.6%) were negative for HCV antibodies. Thus 0.8% of the entire study population was HCV positive but could not be diagnosed by routine HCV antibody testing. Major risk factors identified by a standard questionnaire in 1717 of 2796 patients were the number of blood transfusions individuals had received and duration of dialysis, the latter including patients who received no blood transfusions. Sequencing of the 5'untranslated region of the genome showed a dominant genotype 1 (77.6%) within the cohort. Further reverse transcription-PCR of the NS5b and core region were performed to document phylogenetic analysis. Comparing nucleic acid sequences detected by PCR, no homogeneity was found and thus nosocomial transmission was excluded. CONCLUSIONS: HCV is common in German haemodialysis patients but screening for HCV antibodies alone does not exclude infection with HCV.
BACKGROUND/AIM: Human insulin-like growth factor I (IGF-I) is known to be the mediator of growth hormone dependent proliferation and is responsible for growth-promoting effects in the gastrointestinal tract. Polyamines play an essential role in cell growth and differentiation. The aim of the present study was to investigate the growth-promoting potency of IGF-I in various organ systems simultaneously in rats and the potential role of the polyamine metabolism during IGF-I-induced gastrointestinal growth. METHODS: Based on results of initial dose-response studies, male Wistar rats (150 g) were either treated by subcutaneous injections with (1) IGF-I (1 x 1,000 microg/kg/24 h); (2) IGF-I plus alpha-difluoromethylornithine (3 x 300 mg i.p./kg/24 h plus 2% in drinking water), a specific inhibitor of intracellular polyamine de novo synthesis, or (3) saline (controls). 9-10 animals per group were sacrificed after 5 days of treatment. RESULTS: IGF-I caused a significant (p < 0.005) increase in the weight of small intestine and spleen due to hyperplasia in the small intestine and hypertrophy and hyperplasia in the spleen, while no trophic effects could be observed in stomach or pancreas. The amylase concentration in the pancreas was increased. Simultaneously administered alpha-difluoromethylornithine significantly (p < 0.005) abolished the IGF-I-induced trophic effects in small intestine and spleen. CONCLUSIONS: These data reveal different trophic effects of IGF-I in various organ systems: while significant growth stimulation was found in small intestine and spleen, no proliferation was seen in pancreas and stomach. Polyamines obviously play an important role in IGF-I-mediated gastrointestinal growth.
Gastrin stimulates gastric acid secretion in various species, but the role of the structurally related CCK for the peripheral regulation of acid secretion in humans remains controversial. Moreover, species differences in CCK receptor function and expression have been reported. We therefore sought to identify the cellular targets of CCK and gastrin within the human gastric mucosa in situ. Gastric biopsies were collected from 15 patients without gastric disease. Expression of CCK receptor subtypes was detected in individual cells of the gastric mucosa by reverse transcription (RT)-PCR in situ, immunohistochemistry and confocal laser scanning microscopy, using antisera against the CCK-A or CCK-B/gastrin receptor subtype. Both CCK-A and CCK-B receptors were detected in antral and oxyntic mucosa at the mRNA and protein level. In fundic mucosa, CCK-A receptor mRNA and protein mapped to D cells (37.4+/-7.7). Besides, individual chief cells, mucous neck cells and parietal cells (12.3+/-4.7%) expressed CCK-A receptors. CCK-B/gastrin receptor mRNA and protein were detected in parietal cells (57.4+/-11.1%) and in neuroendocrine cells (33.2+/-4.4%) expressing chromogranin A. Furthermore, epithelial cells within the neck of the gastric gland were found to express the CCK-B/gastrin receptor. We conclude that (i) identification of CCK-A receptors on somatostatin producing D cells in humans provide the anatomical basis for a receptor-mediated mode of action of CCK on somatostatin release and (ii) detection of either CCK receptor subtype in the putative stem cell compartment implies a role of CCK in the maintenance of tissue homeostasis in human gastric mucosa.