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.

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.

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.

[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.

[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.

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.

Diamond stents for palliation of malignant bile duct obstruction: a prospective multicenter evaluation.

BACKGROUND AND STUDY AIMS: Various types of self-expandable metal stents have been introduced for biliary drainage in patients with malignant jaundice, showing prolonged patency compared with plastic endoprostheses. However, there has only been prolonged experience with a meaningful number of patients using the Wallstent. We evaluated the Diamond stent, a self-expanding uncoated biliary metal stent, in a prospective uncontrolled multicenter setting. PATIENTS AND METHODS: The eligibility criterion was obstructive jaundice due to inoperable malignant disease. Between August 1995 and January 2000, 126 patients, who received a total of 134 Diamond stents in four European centers, were followed prospectively. RESULTS: Technical and clinical success rates were 96 % and 98 %, respectively. No major procedure-related complications occurred. The 30-day mortality rate was 13 %. Stent occlusion occurred in 28 patients (22 %). Overall median stent patency was 477 days; overall median survival was 173 days. Stent occlusion, confirmed by endoscopic retrograde cholangiopancreatography, was successfully treated with plastic stents in all patients. Cost analysis revealed estimated costs of 3440 euros per patient for palliative treatment with the Diamond stent. CONCLUSIONS: The Diamond stent compares favorably with other biliary metal stents for patients requiring biliary drainage of malignant jaundice.

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.

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.

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.

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.

Atypical, cytoplasmic and perinuclear anti-neutrophil cytoplasmic antibodies in patients with inflammatory bowel disease.

Atypical, cytoplasmic and perinuclear anti-neutrophil cytoplasmic antibodies (x-, c- and pANCA, respectively) are associated with a variety of inflammatory diseases, including inflammatory bowel disease (IBD). Anti-neutrophil cytoplasmic antibodies are more common in patients with ulcerative colitis (UC) than in patients with Crohn's disease (CD). Most publications only refer to p- and cANCA in relation to IBD. We have prospectively evaluated the reactivity of sera from 58 patients with IBD and 10 healthy controls against human neutrophils with emphasis on the distinction of the ANCA types. The sera were incubated with ethanol- and formaldehyde-fixed granulocytes to differentiate between c-, p- and xANCA. The results showed that 10 of 24 patients with UC were positive for ANCA, whereas only one of 34 patients with CD was ANCA positive. These results correspond to a sensitivity of 42%, a specificity of 97%, a negative predictive value of 91% and a positive predictive value of 75% in UC. Of the 11 ANCA-positive sera, two showed a cytoplasmic staining pattern, three showed a perinuclear and six an atypical staining pattern. The disease activity was not correlated to either the ANCA titre or to the presence of ANCA in the serum. In conclusion, ANCA are of limited value in differentiating between UC and CD. Because the majority of ANCA in patients with IBD are xANCA, these ANCA should be explored by not only incubating on ethanol-fixed granulocytes, but also on formaldehyde-fixed granulocytes.

[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.

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.

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.

Comparison between esophageal Wallstent and Ultraflex stents in the treatment of malignant stenoses of the esophagus and cardia.

BACKGROUND AND STUDY AIMS: Several published studies have examined various self-expanding metal esophageal stents for use in the palliative treatment of esophageal or cardiac neoplasia, but few have compared different self-expanding metal stents. The aim of this study was to evaluate non-covered Wallstent and Ultraflex prostheses in the treatment of malignancies in the esophagus and the cardiac region. MATERIALS AND METHODS: In a retrospective study, the effectiveness of non-covered Wallstents (46 patients) and Ultraflex stents (36 patients) was compared in the treatment of malignancies in the esophageal and cardiac regions. RESULTS: Reintervention procedures were necessary in 16 of the 46 Wallstent patients (six patients during an early phase) and in 22 of the 36 Ultraflex patients (13 during an early phase) (overall P = 0.022; early P = 0.018). The major complication in the Wallstent group was tumor ingrowth (12 of 35 complications), while in the Ultraflex group, it was incomplete deployment (18 of 49 complications). Incomplete stent deployment occurred more often in patients treated with Ultraflex (P = 0.01), and food impaction was more often observed in the Wallstent group (P = 0.001). In addition, in patients with Ultraflex stents, more complex reinterventions were necessary than those required with Wallstents (four vs. 13 complex reinterventions, P = 0.0046). Wallstents tended to improve dysphagia better than Ultraflex stents. CONCLUSION: Compared to Ultraflex stents, Wallstents have several significant short-term and long-term advantages in the palliative treatment of malignancy of the esophagus and cardia.