Ivan Ferkolj

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.

Genetic polymorphism in ATG16L1 gene influences the response to adalimumab in Crohn's disease patients

AIM To see if SNPs could help predict response to biological therapy using adalimumab (ADA) in Crohns disease (CD). MATERIALS & METHODS IBDQ index and CRP levels were used to monitor therapy response. We genotyped 31 CD-associated genes in 102 Slovenian CD patients. RESULTS The strongest association for treatment response defined as decrease in CRP levels was found for ATG16L1 SNP rs10210302. Additional SNPs in 7 out of 31 tested CD-associated genes (PTGER4, CASP9, IL27, C11orf30, CCNY, IL13, NR1I2) showed suggestive association with ADA response. CONCLUSION Our results suggest ADA response in CD patients is genetically predisposed by SNPs in CD risk genes and suggest ATG16L1 as most promising candidate gene for drug response in ADA treatment. Original submitted 24 September 2014; Revision submitted 1 December 2014.

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.

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 3–7 μg/mL, yet data on additional therapeutic benefits and safety of higher trough levels are scarce. Aim: To explore whether high infliximab trough levels (≥7 μg/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 <7 μg/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 66 mg/kg [30–257]; C-reactive protein 3 mg/L [3–3]) compared to trough levels below 7 μg/mL (fecal calprotectin 155 mg/kg [72–474]; C-reactive protein 3 mg/L [3–14.5]) (p < .001). High trough levels were superior also after excluding samples with trough levels <3 μg/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 <7 μg/mL (32/344 [9.3%]) (p = .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.

DNA polymorphisms predict time to progression from uncomplicated to complicated Crohn's disease

Objective Most patients with Crohn’s disease (CD) are diagnosed with the uncomplicated inflammatory form of the disease (Montreal stage B1). However, the majority of them will progress to complicated stricturing (B2) and penetrating (B3) CD during their lifetimes. The aim of our study was to identify the genetic factors associated with time to progression from uncomplicated to complicated CD. Patients and methods Patients with an inflammatory phenotype at diagnosis were followed up for 10 years. Genotyping was carried out using Illumina ImmunoChip. After quality control, association analyses, Bonferroni’s adjustments, linear and Cox’s regression, and Kaplan–Meier analysis were carried out for 111 patients and Manhattan plots were constructed. Results Ten years after diagnosis, 39.1% of the patients still had the inflammatory form and 60.9% progressed to complicated disease, with an average time to progression of 5.91 years. Ileal and ileocolonic locations were associated with the complicated CD (P=1.08E−03). We found that patients with the AA genotype at single-nucleotide polymorphism rs16857259 near the gene CACNA1E progressed to the complicated form later (8.80 years) compared with patients with the AC (5.11 years) or CC (2.00 years) genotypes (P=3.82E−07). In addition, nine single-nucleotide polymorphisms (near the genes RASGRP1, SULF2, XPO1, ZBTB44, HLA DOA/BRD2, HLA DRB1/HLA DQA1, PPARA, PUDP, and KIAA1614) showed a suggestive association with disease progression (P<10−5). Multivariate Cox’s regression analysis on the basis of clinical and genetic data confirmed the association of the selected model with disease progression (P=5.73E−16). Conclusion Our study confirmed the association between the locus on chromosome 1 near the gene CACNA1E with time to progression from inflammatory to stricturing or penetrating CD. Predicting the time to progression is useful to the clinician in terms of individualizing patients’ management.