Liver kidney microsomal type 1 antibodies reduce the CYP2D6 activity in patients with chronic hepatitis C virus infection.

Liver kidney microsomal type 1 (LKM-1) antibodies have been shown to decrease the CYP2D6 activity in vitro and are present in a minority of patients with chronic hepatitis C infection. We investigated whether LKM-1 antibodies might reduce the CYP2D6 activity in vivo. All patients enrolled in the Swiss Hepatitis C Cohort Study and tested for LKM-1 antibodies were assessed (n = 1723): 10 eligible patients were matched with patients without LKM-1 antibodies. Patients were genotyped for CYP2D6 variants to exclude individuals with a poor metabolizer genotype. CYP2D6 activity was measured by a specific substrate using the dextromethorphan/dextrorphan metabolic ratio to classify patients into four activity phenotypes. All patients had a CYP2D6 extensive metabolizer genotype. The observed phenotype was concordant with the CYP2D6 genotype in most LKM-negative patients, whereas only three LKM-1 positive patients had a concordant phenotype (six presented an intermediate and one a poor metabolizer phenotype). The median DEM/DOR ratio was sixfold higher in LKM-1 positive than in LKM-1 negative patients (0.096 vs. 0.016, P = 0.004), indicating that CYP2D6 metabolic function was significantly reduced in the presence of LKM-1 antibodies. In chronic hepatitis C patients with LKM-1 antibodies, the CYP2D6 metabolic activity was on average reduced by 80%. The impact of LKM-1 antibodies on CYP2D6-mediated drug metabolism pathways warrants further translational studies.

Is there an advantage to be gained from adding digital image cytometry of brush cytology to a standard biopsy protocol in patients with Barrett's esophagus?

BACKGROUND AND STUDY AIMS: The current gold standard in Barrett's esophagus monitoring consists of four-quadrant biopsies every 1-2 cm in accordance with the Seattle protocol. Adding brush cytology processed by digital image cytometry (DICM) may further increase the detection of patients with Barrett's esophagus who are at risk of neoplasia. The aim of the present study was to assess the additional diagnostic value and accuracy of DICM when added to the standard histological analysis in a cross-sectional multicenter study of patients with Barrett's esophagus in Switzerland. METHODS: One hundred sixty-four patients with Barrett's esophagus underwent 239 endoscopies with biopsy and brush cytology. DICM was carried out on 239 cytology specimens. Measures of the test accuracy of DICM (relative risk, sensitivity, specificity, likelihood ratios) were obtained by dichotomizing the histopathology results (high-grade dysplasia or adenocarcinoma vs. all others) and DICM results (aneuploidy/intermediate pattern vs. diploidy). RESULTS: DICM revealed diploidy in 83% of 239 endoscopies, an intermediate pattern in 8.8%, and aneuploidy in 8.4%. An intermediate DICM result carried a relative risk (RR) of 12 and aneuploidy a RR of 27 for high-grade dysplasia/adenocarcinoma. Adding DICM to the standard biopsy protocol, a pathological cytometry result (aneuploid or intermediate) was found in 25 of 239 endoscopies (11%; 18 patients) with low-risk histology (no high-grade dysplasia or adenocarcinoma). During follow-up of 14 of these 18 patients, histological deterioration was seen in 3 (21%). CONCLUSION: DICM from brush cytology may add important information to a standard biopsy protocol by identifying a subgroup of BE-patients with high-risk cellular abnormalities.

Diffuse abdominal pain, nausea and vomiting due to retroperitoneal fibrosis: a rare but often missed diagnosis.

Retroperitoneal fibrosis is a rare chronic inflammatory disease usually involving the ureters, retroperitoneal vessels and nerves; however, any intestinal organ may also be involved. In recent years, a few successful immunosuppressive treatments of this disease have been described and surgery can, therefore, probably be avoided in most cases. We report here on a case of secondary retroperitoneal fibrosis with compression and midline deviation of the ureters and impaired renal function which was probably caused by ergotamine abuse because of migraine. The patient complained of diffuse abdominal pain, nausea and vomiting. After immunosuppressive treatment with azathioprine and prednisone for a year, we observed a complete resolution of the retroperitoneal mass on computed tomography, although renal function remained impaired. Eleven months after the cessation of treatment, the patient had not relapsed.

[Headache, fever and upper abdominal colic]. / Kopfschmerzen, Fieber und Oberbauchkoliken.

A nine year old boy who had received Ceftriaxone for one week because of suspected bacterial meningoencephalitis developed colicky abdominal pain in the right upper quadrant two days after termination of Ceftriaxone treatment. Stones in the gallbladder were identified as cause of the abdominal symptoms. Ceftriaxone has been reported to result in so-called pseudo-lithiasis of the gallbladder in approximatively 45% of treated patients, 19% of which developed clinical symptoms. Generally, the gallstones dissolve spontaneously when Ceftriaxone treatment was of short duration.

Endoscopic transgastric debridement and drainage for splenic necrosis following an acute episode in chronic alcoholic pancreatitis.

Management of the complications and sequelae of acute and chronic pancreatitis is a clinical challenge. We report a case of successful transgastric drainage of splenic necrosis after occlusion of the splenic vessels during an acute episode in chronic pancreatitis.

Autofluorescence endoscopy in surveillance of Barrett's esophagus: a multicenter randomized trial on diagnostic efficacy.

BACKGROUND AND STUDY AIMS: The reference surveillance method in patients with Barrett's esophagus is careful endoscopic observation, with targeted as well as random four-quadrant biopsies. Autofluorescence endoscopy (AFE) may make it easier to locate neoplasia. The aim of this study was to elucidate the diagnostic accuracy of surveillance with AFE-guided plus four-quadrant biopsies in comparison with the conventional approach. PATIENTS AND METHODS: A total of 187 of 200 consecutive Barrett's esophagus patients who were initially enrolled (73 % male, mean age 67 years, mean Barrett's segment length 4.6 cm), who underwent endoscopy for Barrett's esophagus in four study centers, were randomly assigned to undergo either AFE-targeted biopsy followed by four-quadrant biopsies or conventional endoscopic surveillance, also including four-quadrant biopsies (study phase 1). After exclusion of patients with early cancer or high-grade dysplasia, who underwent endoscopic or surgical treatment, as well as those who declined to participate in phase 2 of the study, 130 patients remained. These patients were examined again with the alternative method after a mean of 10 weeks, using the same methods described. The main study parameter was the detection of early cancer/adenocarcinoma or high-grade dysplasia (HGD), comparing both approaches in study phase 1; the secondary study aim in phase 2 was to assess the additional value of the AFE-guided approach after conventional surveillance, and vice versa. Test accuracy measures were derived from study phase 1. RESULTS: In study phase 1, the AFE and conventional approaches yielded adenocarcinoma/HGD rates of 12 % and 5.3 %, respectively, on a per-patient basis. With AFE, four previously unrecognized adenocarcinoma/HGD lesions were identified (4.3 % of the patients); with the conventional approach, one new lesion (1.1 %) was identified. Of the 19 adenocarcinoma/HGD lesions detected during AFE endoscopy in study phase 1, eight were visualized, while 11 were only detected using untargeted four-quadrant biopsies (sensitivity 42 %). Of the 766 biopsies classified at histology as being nonneoplastic, 58 appeared suspicious (specificity 92 %, positive predictive value 12 %, negative predictive value 98.5 %). In study phase 2, AFE detected two further lesions in addition to the initial alternative approach in 3.2 % of cases, in comparison with one lesion with conventional endoscopy (1.7 %). CONCLUSIONS: In this referral Barrett's esophagus population with a higher prevalence of neoplastic lesions, the AFE-guided approach improved the diagnostic yield for neoplasia in comparison with the conventional approach using four-quadrant biopsies. However, AFE alone was not suitable for replacing the standard four-quadrant biopsy protocol.

[Conservative medical treatment of chronic pancreatitis]. / Die medizinisch-konservative Behandlung der chronischen Pankreatitis.

The conservative medical treatment of chronic pancreatitis entails dealing prevalently with exocrine and endocrine insufficiency, diet and pain. As steatorrhoea can cause malabsorption, it is advisable to reduce first the fat content of the diet and secondly to prescribe, where necessary, pancreatic enzymes. Several factors can lead to a poor therapeutic enzyme effect. Attention should be given to the pharmacological properties of the enzyme-preparation and to the secretion of acid in the stomach. An endocrine insufficiency is more difficult to treat compared to a classical diabetes mellitus, for lack of endocrine regulatory mechanisms. Pain is the consequence of several pathophysiological processes. Before initiating analgetic treatment, a minimal diagnostic program should be completed allowing the exclusion of those primary causes of pain which require an alternative approach such as interventional endoscopy or surgery.

[Endosonography: a review of applications in gastroenterology]. / Endosonographie: Ein kritischer Uberblick über Anwendungsmöglichkeiten und Grenzen in der Gastroenterologie.

Endosonography is a very important method of investigation in several specialties. It allows the gastroenterologist to reach organs and structures, that may not be seen by percutaneous ultrasound performing a closer imaging of them. Endoscopic ultrasound was initially introduced as a pure diagnostic tool. Nowadays there are many therapeutic interventions that can be done endosonographically. This publication reviews the last development of this method.

[Impact of endoscopic ultrasonography in the diagnosis of aberrant right subclavian artery: a case report]. / Bedeutung der Endosonografie in der Diagnose der Arteria lusoria: eine Fallbeschreibung.

Aberrant right subclavian artery (ARSA) is the most common anomaly of the aortic arch. We present the successful use of endoscopic ultrasonography (EUS) in the diagnosis of ARSA. A 65-year-old woman was admitted because of dyspnoea and inspiratory stridor. Bronchoscopy revealed a subglottic tracheal stenosis. To exclude an underlying malignancy, endoscopy was performed showing an oesophageal impression, which subsequently was identified as ARSA by EUS. Computed tomography excluded neoplasm and confirmed the diagnosis of ARSA. After laser resection of subglottic tissue the stridor resolved and could therefore not be attributed to the co-existence of ARSA. In most cases the ARSA crosses between the oesophagus and the spine from the descending aortic arch to the right and may seldom cause dysphagia due to oesophageal compression. Diagnosis is usually based upon computed tomography or magnetic resonance imaging, whereas angiography is only rarely needed. Endoscopic ultrasonography offers a convenient alternative diagnostic tool and can be performed even as a bedside examination. The diagnosis can be easily assessed in all patients referred for EUS of the upper gastrointestinal tract for any reason. Especially in patients undergoing invasive procedures in the upper thorax or neck, knowledge of an abnormal course of the great vessels is important. Arteria lusoria is often found by chance. EUS is a simple and excellent tool for assessing the diagnosis and usually does not require confirmation through other investigation methods.

[Significance of ursodeoxycholic acid in the eradication of Helicobacter pylori]. / Bedeutung von Ursodeoxycholsäure bei der Eradikation von Helicobacter pylori.

In this pilot study we investigated the value of a fourteen-day regimen with amoxicillin (1 g bid), ranitidine (300 mg/d) and ursodeoxycholic acid (300 mg tid) in eradicating Helicobacter pylori. 15 patients with non-ulcer dyspepsia (reactive CLO test, positive histology or 13C urea breath test) were enrolled. Helicobacter pylori was eradicated in 6 of 13 patients (13C urea breath test 4 weeks after the end of treatment). 2 patients were not followed up because of too short treatment (< 1 week). Only 5/15 patients had no side effects (33%). These results strongly suggest that ursodeoxycholic acid in this application regimen is not of use in eradicating Helicobacter pylori.

[Physician-patient relations and stress caused by coloscopy in patients with chronic inflammatory bowel disease]. / Arzt-Patienten-Beziehung und Belastung durch Koloskopien bei Patienten mit chronisch entzündlicher Darmerkrankung.

The relationship between doctors and patients with inflammatory bowel disease is usually considered complex and difficult. We analyzed the quality of this relationship and the stress inflicted on the patients by endoscopy. 76 patients with Crohn's disease or ulcerative colitis answered a questionnaire. More than three quarters considered their relationship to their doctors good or very good. The patients expressed a wish for more information on the pathophysiology and treatment options of their disease. The stress placed on the patients by endoscopy was considered severe or very severe by 57%. We conclude that the relationship between doctor and patients with inflammatory bowel disease is generally considered good or very good. Endoscopies are highly stressful for most patients and we recommend appropriate sedation.

[Social consequences and quality of life in patients with chronic inflammatory bowel disease]. / Soziale Folgen und Lebensqualität bei Patienten mit chronisch entzündlicher Darmerkrankung.

We conducted a survey on the quality of life and social consequences for patients with inflammatory bowel disease. Questionnaires of 41 patients with Crohn's disease, 28 patients with ulcerative colitis and 7 patients with overlap colitis were evaluated. All the patients had been hospitalized in the past. 15 patients (20%) were unable to work due to inflammatory bowel disease. 9 (12%) of these 15 patients received a disability pension. 11 patients (15%) had to change a place of work and 16 (21%) had had financial problems due to inflammatory bowel disease. 4 patients (5%) had had to give up a partnership due to the disease. For 16% of the patients their perceived quality of life during the past 4 weeks was poor or very poor, while 35% of the patients perceived their overall quality of life as poor or very poor since the beginning of the disease. We conclude that inflammatory bowel disease affects job and financial matters rather than partnerships. The quality of life is judged by many patients as considerably diminished.

[Endoscopic palliation of malignant esophagus processes using a self-expanding metallic stent]. / Endoskopische Palliation maligner Osophagusprozesse mit selbstexpandierenden Metallstents.

We investigated the palliative effect of self-expanding metallic stents on malignant obstruction of the esophagus in 10 patients. All patients had high grade dysphagia and one had an esophago-bronchial fistula. Endoscopic insertions of the prosthesis was done under sedation. Dilatation of the stricture prior to insertion was rarely necessary. Coated stents were used as secondary treatment for patients with fistulae. The procedure related morbidity was low and no mortality was observed. The stents remained patent during the residual lifetime of the patients. Dislocation or perforation did not occur. The median survival of 8 deceased patients was 3.5 months (range 1.25-14.5 months). At present 2 patients are still alive 2.7 and 1.5 months after the procedure. Self-expanding stents in the esophagus provide good palliative therapy of dysphagia or fistulae caused by malignant tumors. Insertion is relatively simple and safer than in nonexpandable types. These improvements may justify the considerably higher price of these devices.

Valproic-acid-induced pancreatitis. Case report and review of the literature.

We report a case of pancreatitis with fatal liver failure, in a 21-year-old, mentally retarded patient, taking valproic acid (VPA) therapy, together with a review of the literature of this rare side effect. Until March 1991, only 24 cases of isolated pancreatitis and six cases (including ours) of pancreatitis with hepatic failure under VPA treatment have been published. Most of the patients were less than 20 years old, and injury to the pancreas developed during the first year of therapy in 72% of the patients, approaching a mortality of 21%. Pancreatitis associated with liver failure has a poor prognosis mainly because of the VPA hepatotoxicity. It seems that the pancreatic side effects fluctuate between two extremes: asymptomatic hyperamylasemia and fatal pancreatitis.

[Enalapril (Reniten)-associated toxic hepatitis]. / Enalapril (Reniten)-assoziierte toxische Hepatitis.

A 52-year-old female was hospitalized with malaise, pruritus, jaundice, abdominal discomfort and vomiting. For 20 weeks she had been taking enalapril (Reniten) for hypertension. Serum aminotransferases and bilirubin were highly elevated with prolonged thromboplastin time. There was no evidence for extrahepatic cholestasis in ultrasonography. Serological investigations for a viral etiology of the liver failure were negative and the patient had no risk factors for viral hepatitis or exposure to hepatotoxic substances. Liver puncture revealed hepatitis of the fulminant viral hepatitis type, a picture that can be seen in a drug-induced hepatitis. The complete recovery of liver function after cessation of enalapril administration suggests acute toxic hepatitis due to enalapril. A metabolically mediated idiosyncratic reaction is the most plausible. Potential mechanisms of enalapril-induced hepatotoxicity are discussed and the current literature is surveyed.

[Acute fatal liver insufficiency due to valproic acid therapy]. / Akute tödliche Leberinsuffizienz unter Valproinsäuretherapie.

Fatal hepatic failure associated with valproic acid therapy is a rare side effect occurring in 1:5000-10,000 of the patients exposed to this antiepileptic drug. Its relevance arises from its fatal outcome and the high number of patients who are treated with this drug (one million worldwide in 1988). 112 cases were published up to 1988. Most of the affected patients were young (less than 10 years old), male, and mentally retarded. Many were under antiepileptic polytherapy. The children of this age group constituted only 23% of the patients treated with valproic acid but 73% of all fatalities. 90% of the patients developed hepatic failure in the first 5 months of therapy. Low doses or therapeutic serum levels of valproic acid do not prevent this dramatic event. Specific therapy is not known. In addition to the case report we review the literature and make recommendations for monitoring therapy with valproic acid.

Utility of abdominal sonography in patients with idiopathic deep vein thrombosis.

PURPOSE: Studies have confirmed an association between idiopathic deep vein thrombosis (DVT) and malignant tumors. We assessed the usefulness of routine abdominal sonography in patients with idiopathic DVT to detect malignant tumors and other relevant findings. METHODS: We retrospectively analyzed abdominal sonograms and records from 135 consecutive patients with confirmed idiopathic DVT and interviewed patients and their physicians during the follow-up period (mean, 30 months). Malignancy and other clinically relevant findings determined by sonography were tabulated, and the cost of each malignancy detected by abdominal sonography in this study was calculated. RESULTS: Malignant tumors were found in 14 patients (10%), 7 by routine abdominal sonography, 3 by other means during hospitalization, and 4 during the follow-up period. Other clinically relevant findings detected by routine abdominal sonography were found in 33 patients (24%). The estimated cost of discovering malignancy by using screening abdominal sonography was approximately US$3,000/malignancy. CONCLUSIONS: Abdominal sonography was useful in detecting a variety of clinically relevant findings in addition to half of the malignant tumors found in our study.

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.

Significance of histologic criteria for the management of patients with malignant colorectal polyps and polypectomy.

BACKGROUND: The management of invasive cancer in colorectal polyps (malignant polyps) is controversial, particularly with regard to the different sets of histologic criteria for deciding whether malignant colorectal polyps should be treated by polypectomy alone or be followed by surgical resection. We report on the outcome of patients in accordance with the histologic assessment of their malignant polyps. METHODS: Malignant polyps were defined as having favourable histology (free margin, grade I or II, and no angiolymphatic invasion) or unfavorable histology (no free margin, grade III, or angiolymphatic invasion). Malignant polyps with favourable histology were treated by endoscopic polypectomy alone, whereas further therapy was recommended for malignant polyps with unfavourable histology. Residual cancer in a resection specimen and local or metastatic recurrence during the follow-up period (mean, 60 months; range, 12 - 120) were defined as adverse outcome. RESULTS: Thirty-seven malignant polyps were detected in 35 (0.5%) of 6605 patients. Five of these 35 patients were treated by primary bowel resection and analysed separately. In the other 30 patients the following unfavourable histologic signs were detected in 20 (62.5%) of 32 malignant polyps; no free margin in 16, grade III in 1, and angiolymphatic invasion in 3 polyps. Twelve polyps with favourable histology had no adverse outcome; in contrast, 5 of 20 polyps with unfavourable histology had an average outcome (P < 0.05). CONCLUSIONS: Locally excised malignant polyps without unfavourable histologic signs may not need further surgical treatment; for all other malignant polyps an ensuing bowel resection is recommended.