Human ileal bile acid transporter gene ASBT (SLC10A2) is transactivated by the glucocorticoid receptor.

BACKGROUND: Patients with Crohn's disease suffer from intestinal bile acid malabsorption. Intestinal bile acid absorption is mediated by the apical sodium dependent bile acid transporter ASBT/IBAT (SLC10A2). In rats, ASBT is induced by glucocorticoids. AIMS: To study whether human ASBT is activated by glucocorticoids and to elucidate the mechanism of regulation. PATIENTS AND METHODS: ASBT expression in ileal biopsies from patients with Crohn's disease and from healthy subjects was quantified by western blot. ASBT promoter function was studied in luciferase assays and by electrophoretic mobility shift assay. RESULTS: In 16 patients with Crohn's disease, ASBT expression was reduced to 69 (7.5)% compared with healthy controls (mean (SEM); p = 0.01). In 10 healthy male volunteers, ASBT protein expression was increased 1.34 (0.11)-fold (mean (SEM); p<0.05) after 21 days' intake of budesonide (9 mg/day) whereas expression of the peptide transporter 1 was unaffected. Reporter constructs of the human ASBT promoter were activated 15-20-fold by coexpression of the glucocorticoid receptor (GR) and exposure to the GR ligands dexamethasone or budesonide. Two glucocorticoid response elements in the ASBT promoter, arranged as inverted hexanucleotide repeats (IR3 elements), conferred inducibility by GR and dexamethasone in a heterologous promoter context and were shown to bind GR in mobility shift assays. CONCLUSIONS: Human ASBT is induced by glucocorticoids in vitro and in vivo. Induction of ASBT by glucocorticoids could be beneficial in patients with Crohn's disease who exhibit reduced ASBT expression. This study identifies ASBT as a novel target of glucocorticoid controlled gene regulation in the human intestine.

[Biliary stents]. / Gallenwegs-Stents.

Endoscopically implantable stents are today the mainstay for therapy of biliary stenoses. It is important to know if a benign or a malignant stenosis is the cause of the biliary obstruction. Generally benign stenoses are treated with plastic-stents whereas malignant stenoses are managed by implantation of a metallic stent. The main indications for plastic stents are postoperative strictures in the biliary tree for example, after biliary tract surgery or liver transplantation, primary sclerosing cholangitis and postoperative biliary leakage. Metallic stents are implanted in palliative circumstances like in stenosing cholangiocarcinoma or in situations where a hepatic metastasis exerts an extrinsic compression on the biliary tract with consecutive cholestasis. The materials used for manufacturing both stent types are biologically inert and thus biocompatible. A current poorly resolved problem is the occlusion of the stent lumen (by sludge, bacterial degradation products etc.) which occurs in both stent types with time. These problems lead to stentocclusion around three to six months after implantation and necessitate endoscopical re-interventions in order to overcome the occlusion. The patency rate for metallic stents is better than for plastic ones. The endoscopic stenttherapy is equivalent to surgical therapy (Intestinal bypass-procedures).

Diagnostic quality of biopsy specimens: comparison between a conventional biopsy forceps and multibite forceps.

BACKGROUND: The endoscopic biopsy is a prerequisite for histopathologic diagnosis. Various types of forceps are used to obtain tissue specimens. The aim of this study was to assess and compare the diagnostic quality of biopsy specimens obtained with a conventional forceps and a Multibite forceps. METHODS: In a prospective, partially blinded, and randomized trial that included 250 patients referred for diagnostic upper and/or lower endoscopy, 510 biopsy specimens obtained with the Multibite forceps were compared with 520 specimens obtained with a conventional forceps. An experienced, blinded pathologist evaluated the specimens for diameter, depth of specimen, artifacts, anatomic orientation, vitality, general histologic quality, and diagnostic quality. Statistical analysis was performed by using the Fisher exact test. A p value of < 0.05 was regarded as significant. RESULTS: There were no statistically significant differences between the specimens obtained with the 2 forceps. The p values for the evaluated parameters were as follows: diameter 0.45, depth of specimen 0.56, artifacts 1.0, pathoanatomic orientation 0.40, vitality 0.45, and histologic diagnostic quality 0.53. CONCLUSION: The quality of biopsy specimens obtained with the Multibite forceps is comparable with that of specimens taken with a conventional forceps. Use of the Multibite forceps saves time in that 4 specimens can be obtained in 1 pass in situations in which a large number of specimens are needed or when the potential for transmission of infection is of concern.

Safer colonoscopy with patient-controlled analgesia and sedation with propofol and alfentanil.

BACKGROUND: The aim of this study was to assess the efficacy of patient-controlled analgesia and sedation with propofol/alfentanil for colonoscopy compared with continuous drug infusion and conventional nurse-administered medication. METHODS: One hundred fifty patients undergoing colonoscopy on an outpatient basis were randomly assigned to 1 of 3 medication regimens. To maintain blinding, all patients were connected to an infusion pump. Group I patients could self-administer boluses of 4.8 mg propofol and 125 microg alfentanil without restriction. Group II patients received a continuous infusion with 0.048 mg/kg propofol and 0.12 microg/kg alfentanil per minute. Group III patients received intravenous premedication with 0.035 mg/kg midazolam and 0.35 mg/kg meperidine. RESULTS: There were no differences between the groups with respect to pain (visual analogue scale) and procedure time. Patient-controlled analgesia and sedation with propofol/alfentanil (group I) resulted in less of an increase in the transcutaneous partial pressure of carbon dioxide (p = 0.0004) during colonoscopy and less of a decrease in mean arterial blood pressure (p = 0.0021) during recovery, as well as more complete recovery (p = 0.0019) after 45 minutes compared with conventional administration of midazolam/meperidine. Furthermore, patient-controlled analgesia and sedation yielded a higher degree of patient satisfaction than continuous infusion of propofol/alfentanil (p = 0.0033) or nurse-administered midazolam/meperidine (p = 0.0094). CONCLUSIONS: Patient-controlled administration of propofol and alfentanil for colonoscopy may provide a better margin of safety than conventional administration of midazolam and meperidine and results in a higher level of patient satisfaction and shorter recovery.

Cytomegalovirus-induced transient protein-losing hypertrophic gastropathy in an immunocompetent adult.

Transient protein-losing hypertrophic gastropathy with similarity to Ménétrier's disease is described. Acute infection with cytomegalovirus (CMV) could be shown to play a causative role. Immunodeficiency was ruled out. The 34-year-old patient had complete resolution of the disease without antiviral treatment. To our knowledge the present report is the first case of CMV-associated protein-losing hypertrophic gastropathy in an immunocompetent adult. To date, a similar disorder has only been described in children. CMV infection should be considered in patients with acute and symptomatic protein loss of gastrointestinal origin.

Esophageal carcinoma: current staging strategies.

A patient with suspected esophageal carcinoma represents a challenge to the treating physicians. Most patients present with an advanced stage of disease, and in the majority of cases only palliative treatment can be offered. Various treatment modalities are available, which are applied according to the TNM stage of the disease and the performance status of the patient. A precise histological diagnosis and highly accurate tumor staging of a patient with esophageal carcinoma is a prerequisite for the selection of the most suitable treatment option. Endoscopic ultrasound (EUS) has emerged as the most accurate diagnostic modality for locoregional staging. Problems in identifying early tumor stages or tumor strictures can be generally overcome by using miniprobe sonography (MPS). EUS/fine-needle aspiration biopsy (FNA) technology provides a valuable means of identifying suspicious locoregional lymph nodes. Patients with a proximal tumor (trachea bifurcation) should undergo bronchoscopy to rule out infiltration of the tracheobronchial system. Ultrasound (US), computed tomography (CT), and possibly magnetic resonance imaging (MRI) are the diagnostic tools of choice for extended tumor staging. After excluding extended tumor stage and severe concomitant diseases, diagnostic laparoscopy with intra-abdominal ultrasound should be performed in patients with adenocarcinoma of the esophagus prior to esophagectomy. Intra-abdominal metastases which can be missed preoperatively in some cases have to be ruled out in order to avoid unnecessary surgery.

Attitude to Helicobacter pylori infection among Swiss gastroenterologists.

OBJECT: To assess the current attitude to Helicobacter pylori infection in Switzerland, since a review of the literature reveals few publications dealing with application of therapeutic recommendations. METHODS: The initial diagnostic methods, the indications for eradication therapy, the therapeutic regimen and its duration, together with eradication control, were indicated in questionnaires sent out to the members of the Swiss Society for Gastroenterology and Hepatology at the beginning of 1997. RESULTS: Helicobacter pylori was diagnosed mainly with a rapid urease test and/or histology. Peptic ulcer disease (100%), mucosa associated lymphoid tissue (MALT) lymphoma (94.5%) and therapy-resistant dyspepsia (78.7%) were clear indications for Helicobacter pylori eradication. Only a minority eradicated Helicobacter pylori in all positive subjects. 7-day triple therapy (with proton pump inhibitors, a macrolide antibiotic and an imidazole derivative) is the preferred first line treatment. CONCLUSIONS: The eradication of Helicobacter pylori in ulcer disease is established practice. Non-ulcer dyspepsia remains a controversial but often used indication. Two antibiotics together with proton pump inhibitors constitute the mostly widely used eradication therapy.

Argon beam coagulation for treatment of symptomatic radiation-induced proctitis.

BACKGROUND: Radiation proctitis is a complication of radiotherapy for malignant pelvic disease. Argon beam coagulation is a new and rapidly evolving technology that permits a "no-touch" electrocoagulation of diseased tissue. METHODS: We analyzed retrospectively the records of 7 patients with prostatic and endometrial cancers treated with irrradiation (median radiation dose was 6840 cGy, range 2400 to 7200 cGy). The median time to onset of symptoms after the conclusion of radiotherapy was 20 months (range 16 to 48 months); symptoms consisted of rectal bleeding and tenesmus in all patients. The patients underwent argon beam coagulation after colonoscopic evaluation. The usual treatment interval was 3 weeks (range 1 to 3 weeks). RESULTS: A median of 2 treatment sessions (range 2 to 4) was necessary for complete symptom relief. All interventions were well tolerated without complications. During follow-up (median 24 months, range 18 to 24 months), there was no recurrence of symptoms (bleeding, tenesmus). CONCLUSIONS: Argon beam coagulation is a safe, well tolerated, and effective treatment option in symptomatic radiation proctitis.

[Diarrhea as initial manifestation of medullary thyroid carcinoma]. / Diarrhoe als Erstmanifestation eines medullären Schilddrüsenkarzinoms.

HISTORY AND CLINICAL FINDINGS: For 15 months a 52-year-old business man had been suffering from chronic diarrhoea which had persisted even after exophthalmic hyperthyroidism (Grave's disease) had been diagnosed and adequately treated. Physical examination on admission revealed no abnormalities, in particular no sign of hyperthyroidism. INVESTIGATIONS AND DIAGNOSIS: Repeated stool examinations failed to demonstrate any infectious organisms. Upper gastrointestinal endoscopy and ileaocoloscopy were normal, as were biopsies. Persistence of the diarrhoea during a fasting test and the bulky stools suggested a secretory cause. Among various hormonal tests the calcitonin concentration was found to be greatly raised (4572 ng/l, normal 10 < ng/l). Ultrasound demonstrated a thyroid tumour and cytological examination of a fine-needle biopsy revealed a medullary carcinoma. TREATMENT AND COURSE: After total thyroidectomy with bilateral neck dissection the patient was free of any symptoms: the diarrhoea ceased immediately after the operation and the calcitonin concentration became nearly normal. CONCLUSIONS: Signs of chronic secretory diarrhoea suggest the possibility of an endocrinally active tumour. Search for a medullary carcinoma of the thyroid with measurement of the serum calcitonin level should be among the diagnostic procedures.

Bleeding anorectal varices: successful treatment with transjugular intrahepatic portosystemic shunting (TIPS).

A patient with severe recurrent rectal bleeding from anorectal varices due to portal hypertension because of hepatitis C virus related liver cirrhosis is presented. As illustrated by the report, it is essential to differentiate bleeding anorectal varices from bleeding haemorrhoids because treatment is different. In our patient, implantation of a transjugular intrahepatic portosystemic shunt (TIPS) led to an impressive regression of the anorectal varices, which could be demonstrated by sigmoidoscopy, endosonography, and magnetic resonance imaging. Recurrent rectal bleeding in a patient with portal hypertension should alert the physician to consider anorectal varices. Endoscopic ultra-sound and magnetic resonance imaging are new and non-invasive modalities for diagnosis and post-treatment control.