Soluble extracts from Helicobacter pylori induce dome formation in polarized intestinal epithelial monolayers in a laminin-dependent manner.

Helicobacter pylori colonizes the stomach at the interface between the mucus layer and the apical pole of gastric epithelial cells. A number of secreted and shed products from the bacteria, such as proteins and lipopolysaccharide, are likely to have a role in the pathogenesis at the epithelial level. To determine the physiological response of transporting polarized epithelia to released soluble factors from the bacterium, we used the T84 cell line. Monolayers of T84 cells were exposed to soluble extracts from H. pylori. The extracts induced rapid "dome" formation as well as an immediate decrease in transepithelial electrical resistance. Domes are fluid-filled blister-like structures unique to polarized epithelia. Their formation has been linked to sodium-transporting events as well as to diminished adherence of the cells to the substrate. H. pylori-induced dome formation in T84 monolayers was exacerbated by amiloride and inhibited by ouabain. Furthermore, it was associated with changes in the expression of the laminin binding alpha 6 beta 4 integrin and the 67-kDa laminin receptor. Domes formed primarily on laminin-coated filters, rather than on fibronectin or collagen matrices, and their formation was inhibited by preincubating the bacterial extract with soluble laminin. This effect was specific to H. pylori and independent of the urease, vacA, cagA, and Lewis phenotype of the strains. These data indicate that released elements from H. pylori can alter the physiological balance and integrity of the epithelium in the absence of an underlying immune response.

Transvenous liver biopsy via the femoral vein.

AIM: To study the safety, effectiveness and diagnostic value of transvenous forceps biopsy of the liver in 54 patients with coagulopathy, gross ascites or morbid obesity and suspected liver disease in whom percutaneous liver biopsy was contraindicated. MATERIAL AND METHODS: Forceps biopsy of the liver via the femoral vein was attempted in 54 adult patients with advanced liver disease of unknown aetiology who had coagulation disorders (41 cases), gross ascites (11 cases) or morbid obesity (two cases). In each patient two to six biopsies (average four) were taken using a radial jaw forceps inserted via the right or left femoral vein. RESULTS: The procedure was successful in 53 cases. Hepatic vein catheterization failed in one patient. Adequate liver tissue for diagnosis was obtained in 84% of cases. One patient developed delayed haemorrhage at 12 h from a capsular leak that was undetected during the biopsy procedure. This patient required blood transfusions and laparotomy to control bleeding. There were no deaths in the 53 patients studied. Transient minor chest and shoulder pain was encountered during sheath insertion into a hepatic vein in 23 patients. Three patients developed a femoral vein haematoma, which resolved with conservative treatment. CONCLUSION: Transvenous liver biopsy via the femoral vein is another safe, effective, simple alternative technique of biopsy when the percutaneous route is contraindicated.

Patient knowledge and educational needs in irritable bowel syndrome.

OBJECTIVE: Educating patients with irritable bowel syndrome (IBS) about their disorder may promote a strong physician-patient interaction, is a recommended approach for treating mild IBS and may reduce healthcare use. Our aim was to identify the information needs, levels and associated factors in IBS, and to contrast this with patients with inflammatory bowel disease (IBD). DESIGN: Seventy adult IBS patients (Rome criteria) were prospectively recruited, together with 82 ulcerative colitis (UC) and 60 Crohn's disease (CD) patients. Demographic data, clinical data, and anxiety and depression scores (HAD scale) were recorded. Patients rated their perceived levels of disease knowledge and satisfaction with their knowledge level on visual analogue scales. Qualitative data on disease information needs were obtained by an open-ended question. SETTING: Gastroenterology out-patient clinic. RESULTS: The majority of IBS patients (77%; n = 54) and over half of IBD patients (56%; n = 79) required further information about their disease. The primary issues for IBS patients were bowel cancer risk and diet. Queries about medications ranked top for UC, while prognosis and cancer risk jointly ranked top for CD. In the IBS group, 27% rated their knowledge as < 25 out of 100 compared to 10% of IBD patients. The perceived level of knowledge in IBS was significantly negatively associated with length of hospital consulting (r(s) = -0.32; P = 0.04). CONCLUSION: Most IBS patients feel insufficiently informed, particularly in relation to risk of serious disease and role of diet. Educating IBS patients about their disorder may play a role in reducing healthcare use.

Carcinoma of the ampulla of Vater: a tumour with a poor prognosis?

OBJECTIVE: To assess the overall prognosis of patients with ampullary carcinomas and evaluate the presentation, diagnosis, pathology and management of these potentially highly curable tumours, attempting to relate these factors to overall survival. PATIENTS AND METHODS: Forty patients with ampullary carcinoma were reviewed. Age, Sex, nature and duration of history, laboratory information at admission, results of diagnostic radiology, endoscopic retrograde cholangiopancreatograms and pathological findings were considered. Both curative and palliative management strategies were reviewed. RESULTS: The overall median survival was 19 months. The median duration of history was 5.9 +/- 5.4. weeks, with no significant difference in survival between patients with short and those with long histories (P = 0.46). Twenty nine (73%) patients were potentially resectable, but only 15 (37%) underwent potentially curative surgery. The difference in survival between the Whipple's (13) and the endoscopically stented (20 ) groups was not significant (p = 0.08). The Whipple's group were significantly younger than the stented group (P = 0.001) and had a significant operative morbidity, re-operation rate (38%) and post-operative mortality (15%). Only five of 13 patients were alive following Whipple's treatment after a mean follow-up of 18.9 months. Sphincterotomy before Whipple's treatment improved survival significantly (P = 0.04); absence of jaundice, exophytic macroscopic appearance, well-differentiated tumours and early stage were also associated with good survival. Endoscopic retrograde cholangiopancreatography has a high diagnostic yield and a low associated morbidity and mortality, with endoscopic papillectomy aiding cannulation while effective palliation was provided through stenting, endoscopic papillectomy and laser debulking of obstructing tumours. Little benefit was obtained from chemoradiotherapy. CONCLUSION: Despite the potential for curative resection in patients with ampullary carcinoma, the majority of such patients are unsuitable for curative surgery on grounds of age, general health status or advanced disease; since only 37% of patients undergo potentially curative surgery the condition has a poor prognosis.

A metastatic neuroendocrine anaplastic small cell tumor in a patient with multiple endocrine neoplasia type 1 syndrome. Assessment of disease status and response to doxorubicin, cyclophosphamide, etoposide chemotherapy through scintigraphic imaging with 111In-pentetreotide.

Extrapulmonary small cell and small cell neuroendocrine tumors of unknown primary site are, in general, aggressive neoplasms with a short median survival. Like small cell lung cancer (SCLC), they often are responsive to chemotherapy and radiotherapy. Small cell lung cancer and well differentiated neuroendocrine carcinomas of the gastrointestinal tract and pancreas tend to express somatostatin receptors. These tumors may be localized in patients by scintigraphic imaging using radiolabeled somatostatin analogues. A patient with anaplastic neuroendocrine small cell tumor arising on a background of multiple endocrine neoplasia type 1 syndrome is reported. The patient had a known large pancreatic gastrinoma and previously treated parathyroid adenopathy. At presentation, there was small cell cancer throughout the liver and skeleton. Imaging with a radiolabeled somatostatin analogue, 111In-pentetreotide (Mallinckrodt Medical B. V., Petten, Holland), revealed all sites of disease detected by routine biochemical and radiologic methods. After six cycles of chemotherapy with doxorubicin, cyclophosphamide, and etoposide, there was almost complete clearance of the metastatic disease. 111In-pentetreotide scintigraphy revealed uptake consistent with small areas of residual disease in the liver, the abdomen (in mesenteric lymph nodes), and posterior thorax (in a rib). The primary gastrinoma present before the onset of the anaplastic small cell cancer showed no evidence of response to the treatment. The patient remained well for 1 year and then relapsed with brain, lung, liver, and skeletal metastases. Despite an initial response to salvage radiotherapy and chemotherapy with carboplatin and dacarbazine, the patient died 6 months later.