Borut Štabuc

Acute biliary pancreatitis : detection of common bile duct stones with endoscopic ultrasound

Objectives To determine prospectively the sensitivity and specificity of endoscopic ultrasound (EUS) for detecting common bile duct stones (CBS) in patients with acute biliary pancreatitis in whom transabdominal ultrasound was negative for CBS. Methods In 38 consecutive patients with acute biliary pancreatitis who were negative for CBS by transabdominal ultrasound, EUS was performed before endoscopic retrograde cholangiopancreatography (ERCP). The endoscopist performing ERCP was blind to the results of EUS. The primary goal of EUS and ERCP was to confirm or exclude CBS. The reference standard for CBS was endoscopic extraction of bile duct stones after endoscopic sphincterotomy. When both procedures, EUS and ERCP excluded CBS, it was assumed that there were no CBS and endoscopic sphincterotomy was not performed. The results EUS and ERCP were compared with the McNemar test. Results Twenty-five of the 38 patients (66%) had CBS. EUS and ERCP were false negative in one patient each, EUS was false positive in two patients and ERCP in one patient. The sensitivity of both EUS and ERCP was 96%. The specificity of EUS and ERCP was 85 and 92%, respectively. The difference between EUS and ERCP was not significant (P=0.9). Conclusion EUS proved to be as sensitive as ERCP for detection of CBS in patients with acute biliary pancreatitis. Therefore, EUS could be used as the first-line procedure in patients with acute biliary pancreatitis when therapeutic ERCP is not needed. By this approach a substantial number of unnecessary diagnostic ERCP procedures could be avoided.

Down‐regulation of microRNAs of the miR‐200 family and up‐regulation of Snail and Slug in inflammatory bowel diseases — hallmark of epithelial−mesenchymal transition

Fibrosis is an important feature of inflammatory bowel diseases (IBD), particularly Crohns disease (CD), but its pathogenesis is poorly understood. To determine the postulated involvement of epithelial−mesenchymal transition (EMT) in the development of fibrosis in IBD, we analysed the expression profiles of the miR‐200 family which has been shown to induce EMT in experimental models and various human diseases. We also analysed the expression of Snail and Slug, postulated targets of the investigated microRNAs. Ten patients with ulcerative colitis (UC) and 10 patients with CD who underwent colon resection were included. From each, two tissue samples were chosen (one with the most severely and one with the least affected or normal mucosa) for analysis of microRNAs expression using real‐time polymerase chain reaction, and Snail and Slug expression using immunohistochemistry. We found significant down‐regulation of all investigated microRNAs in CD, and of three investigated microRNAs in UC, in comparison to the normal or the least affected mucosa. Comparing UC and CD, four microRNAs were significantly more down‐regulated in CD than in UC. Snail and Slug were expressed in the injured epithelium and occasionally in mesothelial cells and submesothelial fibroblasts. Our finding of down‐regulation of the miR‐200 family and up‐regulation of transcription repressors Snail and Slug supports the postulated role of EMT in the pathogenesis of fibrosis in IBD. The described expression patterns are consistent with the notion that fibrosis does not occur only in CD but also in UC, being much more severe in CD.

Diagnosing cytomegalovirus in patients with inflammatory bowel disease—by immunohistochemistry or polymerase chain reaction?

Cytomegalovirus (CMV) reactivation is a common complication in patients with inflammatory bowel diseases (IBD), particularly in those with steroid-resistant ulcerative colitis. It is usually diagnosed by histopathologic and immunohistochemical examination of the colon biopsy. The introduction of quantitative, real-time polymerase chain reaction (qPCR) has been recommended to improve the sensitivity, but there is little consensus on how to use it. We compared the two methods in samples from resected bowel of patients with IBD. Twelve patients with IBD who had undergone bowel resection were analysed for CMV, using qPCR and immunohistochemistry. In all cases, tissue samples from the base and the edge of ulcers and from uninvolved mucosa were obtained. The highest densities of CMV-positive cells were found in samples from the base of ulcers (immunohistochemistry 0–0.47 positive cells/mm2; qPCR 10–3809 viral copies/mg) or the edge of ulcers (immunohistochemistry 0.06–0.32 positive cells/mm2; qPCR 35–1049 viral copies/mg). In samples of uninvolved mucosa, immunohistochemistry was negative, whereas qPCR was either negative or showed very low values (0–3 viral copies/mg). We conclude that both immunohistochemistry and qPCR can be successfully used for diagnosing CMV reactivation in patients with IBD. The base and the edge of ulcers are the optimal sites for endoscopic biopsies. The density of CMV-positive cells was low and their distribution within the colon uneven. It therefore seems that the number of sampled biopsies and/or the number of investigated levels is more important that the choice of diagnostic method.

Results of the Fit-based National Colorectal Cancer Screening Program in Slovenia

Background: Colorectal cancer (CRC) is one of the most common malignancies in the western world. Objective: We aimed to assess the first round of fecal immunochemical test (FIT)-based National CRC screening program (NCSP). Methods: In the NCSP conducted in Slovenia, a FIT and colonoscopy for those tested positive was used. The NCSP central unit sent 536,709 invitations to Slovenian residents age 50 to 69 years old between 2009 and 2011. The adherence rate was 56.9% (303,343 participants). FIT was positive in 6.2% (15,310) of the participants (men, 7.8%; women, 5.0%; P<0.01). A total of 13,919 unsedated colonoscopies were performed with the cecal intubation rate of 97.8%. Results: The overall adenoma detection rate was 51.3% [95% confidence interval (CI), 50.5%-52.1%] of which 61.0% (95% CI, 59.9%-62.1%) was in men, and 39.1% (95% CI, 37.8%-40.3%) in women (P<0.01). The mean number of adenoma per positive colonoscopy was 1.94 (95% CI, 1.90-1.97). Adenoma, advanced adenoma, or cancer were found in 7732 (55.5%) colonoscopies. A total of 862 (6.2%) CRC cases were found. Only 161 (18.7%) carcinomas were situated in the right colon. A total of 597 (70.2%) patients with cancer were in the early clinical stages (N, negative; 194 22.8%) of all cancers were cured with only endoscopic resection. Conclusions: In the NCSP, CRC was found in 6.2% of those participants attending colonoscopy, with 81.3% of carcinomas found in the left colon. A localized clinical stage was found in 70.2% participants. In 22.8% of CRC patients, cancer was cured with endoscopic resection only.

Fatal hemorrhage due to thrombosis and rupture of the portal vein and hepatic artery

ZusammenfassungEine Thrombose der Pfortader ist ein relativ häufig vorkommendes klinisches Ereignis, das im Allgemeinen nicht lebensbedrohlich ist, aber doch Anlass für ernsthafte Komplikationen sein kann. Wir berichten über eine Frau, die bis zum 50. Lebensjahr immer gesund war. Im Alter von 50 Jahren entwickelte sie eine akute Gastroenterokolitis mit Entzündung der Pfortader (Pylephlebitis oder septische portale Thrombophlebitis), durch die es zu Thrombusbildung, Ruptur der Gefäßwand und schließlich fataler Blutung kam. Bei der Obduktion konnten nirgendwo anders in ihrem Körper Zeichen von Thrombose oder Entzündung gefunden werden. Es konnte auch kein Hinweis auf das Vorliegen irgend einer anderen Erkrankung oder Abnormalität gefunden werden. Eine Pylephlebitis kann nach einer intraabdominellen Sepsis jedweden Ursprungs vorkommen. Sie ist ein seltenes Ereignis, das mit einer hohen Mortalität einhergeht. Die Ruptur der entzündeten Pfortader und möglicherweise der anliegenden Arterie stellt eine extrem seltene Komplikation dar.SummaryPortal vein thrombosis is a fairly common clinical condition that is usually not fatal but may give rise to serious complications. We report the case of a woman who was always in good health until the age of 50, when she developed acute gastroenterocolitis with inflammation of the portal vein (pylephlebitis or septic portal thrombophlebitis), resulting in thrombus formation, rupture of the vascular wall and exsanguination. At autopsy, no signs of thrombosis or inflammation were found elsewhere in the body and there was no evidence of any other disease or abnormality. Pylephlebitis may occur following intra-abdominal sepsis from any source. It is a rare condition that carries a high mortality. Rupture of the inflamed portal vein and possibly the adjacent artery is an extremely rare complication.

Success and safety of high infliximab trough levels in inflammatory bowel disease

Abstract Objective: A prospective trial suggests target infliximab trough levels of 3–7u2009μg/mL, yet data on additional therapeutic benefits and safety of higher trough levels are scarce. Aim: To explore whether high infliximab trough levels (≥7u2009μg/mL) are more effective and still safe. Material and methods: In this cohort study of 183 patients (109 Crohn’s disease and 74 ulcerative colitis) on infliximab maintenance treatment at a tertiary referral center we correlated fecal calprotectin and C-reactive protein to trough levels (426 samples) at different time points during treatment. Rates of infections were compared in quadrimesters (four-month periods) with high trough levels to quadrimesters with trough levels <7u2009μg/mL during 420 patient-years. Results: Fecal calprotectin and C-reactive protein (median [interquartile range]) were lower in patients with high trough levels (fecal calprotectin 66u2009mg/kg [30–257]; C-reactive protein 3u2009mg/L [3–3]) compared to trough levels below 7u2009μg/mL (fecal calprotectin 155u2009mg/kg [72–474]; C-reactive protein 3u2009mg/L [3–14.5]) (pu2009<u2009.001). High trough levels were superior also after excluding samples with trough levels <3u2009μg/mL from analysis. No differences in rates of infections were observed in quadrimesters with high trough levels (16/129 [12.4%]) compared to quadrimesters with trough levels <7u2009μg/mL (32/344 [9.3%]) (pu2009=u2009.32). Maintaining high trough levels resulted in 32% (interquartile range: 2–54%) increase of infliximab consumption. Conclusion: High infliximab trough levels provide better control of inflammation in inflammatory bowel disease without increasing the risk of infection.

Clinically important neutralizing anti-drug antibodies detected with an in-house competitive ELISA

Therapeutic drug monitoring of TNF-alpha inhibitors is crucial for evaluating patients with inflammatory diseases on a personalized level. It has been clinically observed that many patients receiving TNF-alpha inhibitors, with negative drug and anti-drug antibody results from bridging ELISA (bELISA), lose their drug response over time, despite dose optimization. Our aims were to develop innovative in-house competitive ELISAs (cELISAs) for the detection of neutralizing antibodies against infliximab and adalimumab and compare their results to reporter gene assay (RGA) and in-house bELISA. Furthermore, we aimed to evaluate patient anti-drug antibody results in regard to their clinical records and potential benefits of therapeutic drug monitoring with the novel cELISAs. Sera of patients treated with infliximab (nu2009=u200946) or adalimumab (nu2009=u200931), having undetectable drug levels, were tested with our in-house cELISA. Briefly, samples were incubated with a fixed amount of drug and the neutralizing capacity of the samples was determined. The cELISA results were compared to RGA and bELISA results using Spearman’s correlation coefficient. Additionally, patient clinical data were evaluated in line with the results of cELISA, bELISA, and RGA using the Kaplan-Meier analysis and the Log Rank test. Both anti-infliximab and anti-adalimumab cELISAs showed very good correlation to RGA (ru2009=u20090.932, pu2009<u20090.0001 and ru2009=u20090.947, pu2009<u20090.0001, respectively). Furthermore, a positive result in anti-infliximab cELISA can predict treatment failure in 100% of patients with negative bELISA, while a positive result in anti-adalimumab cELISA can predict treatment failure in 80% of patients with negative bELISA. Taken together, we developed innovative cELISAs enabling quantification of functional and neutralizing anti-drug antibodies, comparable to RGA. The association between cELISA results and loss of drug response in patients identified clinically important anti-drug antibodies, as measured by cELISA.

Sarcoidosis and Collagenous Colitisâ Important Clinical Association orCoincidence?

We present a case of a 57-year-old woman with two rare concomitant diseases; sarcoidosis and collagenous colitis. Patient was admitted to our hospital with the symptoms of watery diarrhea that intermittently lasted for years because of delayed diagnosis. Despite increasing awareness of microscopic colitis, the delayed diagnosis remains an important problem. Diagnosis was quickly confirmed with flexible proctosigmoidoscopy. Rectal biopsies were sufficient for diagnosis. Symptoms improved dramatically the second day of the induction therapy with budesonide. Causal relationship between sarcoidosis and microscopic colitis is not yet confirmed, and to our knowledge, this is the first such case report.