The additive value of CA19.9 monitoring in a pancreatic cyst surveillance program

Background:Surveillance of pancreatic cysts focuses on the detection of (mostly morphologic) features warranting surgery. European guidelines consider elevated CA19.9 as a relative indication for surgery. We aimed to evaluate the role of CA19.9 monitoring for early detection and management in a cyst surveillance population. Methods: The PACYFIC-registry is a prospective collaboration that investigates the yield of pancreatic cyst surveillance performed at the discretion of the treating physician. We included participants for whom at least one serum CA19.9 value was determined by a minimum follow-up of 12 months.Results: Of 1865 PACYFIC participants, 685 met the inclusion criteria for this study (mean age 67 years, SD 10; 61% female). During a median follow-up of 25 months (IQR 24, 1966 visits), 29 participants developed high-grade dysplasia (HGD) or pancreatic cancer. At baseline, CA19.9 ranged from 1 to 591 kU/L (median 10 kU/L [IQR 14]), and was elevated (≥37 kU/L) in 64 participants (9%). During 191 of 1966 visits (10%), an elevated CA19.9 was detected, and these visits more often led to an intensified follow-up (42%) than those without an elevated CA19.9 (27%; p &lt; 0.001). An elevated CA19.9 was the sole reason for surgery in five participants with benign disease (10%). The baseline CA19.9 value was (as continuous or dichotomous variable at the 37 kU/L threshold) not independently associated with HGD or pancreatic cancer development, whilst a CA19.9 of ≥ 133 kU/L was (HR 3.8, 95% CI 1.1–13, p = 0.03). Conclusions: In this pancreatic cyst surveillance cohort, CA19.9 monitoring caused substantial harm by shortening surveillance intervals (and performance of unnecessary surgery). The current CA19.9 cutoff was not predictive of HGD and pancreatic cancer, whereas a higher cutoff may decrease false-positive values. The role of CA19.9 monitoring should be critically appraised prior to implementation in surveillance programs and guidelines.</p

Willingness to undergo colonoscopy with virtual reality instead of procedural sedation in analgesia

OBJECTIVE: This study explored the willingness of patients to start colonoscopy with virtual reality (VR) instead of procedural sedation and analgesia (PSA), as well as their motives and characteristics. There is a growing interest in colonoscopy without PSA. Offering VR as a distraction technique instead of PSA may increase the percentage of colonoscopies without PSA. PATIENTS AND METHODS: A survey with demographic, colonoscopy-related and psychology-related questions was completed by 326 adults referred for colonoscopy with PSA. RESULTS: Overall, 25.7% reported to be willing to start with VR instead of PSA. Main reasons for this choice were receiving as little medication as possible, resuming daily life activities faster and participating in traffic independently afterwards. Logistic regression analysis showed that significant predictors of the willingness to use VR were male sex, higher educational level and absence of worries about the outcome of the colonoscopy. CONCLUSION: If VR turns out to be effective in the future, present results may be useful to customize patient information to help patients choosing VR

Acute hepatitis B in a healthcare worker: A case report of genuine vaccination failure

Background: Individuals who reach the antibody threshold level of 10 IU/I against the surface protein of the hepatitis B virus (HBV) after completion of a series of hepatitis B vaccination are considered to be long-term protected against a clinically manifest HBV infection. Case report: Here we describe an acute hepatitis B infection in a patient who received five hepatitis B vaccinations. Although his initial response to vaccination was moderate, he finally reached an excellent hepatitis B surface antibody level (anti-HBs) titres of more than 1000 IU/I in response to a booster vaccination with a recombinant DNA vaccine. Nevertheless, he developed full-blown acute hepatitis due to an HBV infection 14 years after this booster vaccination. A DNA analysis of the surface protein encoding region followed by phylogenetic analysis showed that our patient was infected with a normal HBV strain that is circulating among men who have sex with men. To our knowledge, this is the first report of a genuine hepatitis B vaccination failure in someone who acquired a high anti-HBs level in response to a recombinant DNA hepatitis B vaccine. Conclusion: Healthcare workers whose response to the initial hepatitis B vaccination is moderate might be vulnerable to hepatitis B virus infection. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved

Relative contributions of NOS isoforms during experimental colitis: endothelial-derived NOS maintains mucosal integrity

The role of nitric oxide (NO) in inflammatory bowel diseases has traditionally focused on the inducible form of NO synthase (iNOS). However, the constitutive endothelial (eNOS) and neuronal (nNOS) isoforms may also impact on colitis, either by contributing to the inflammation or by regulating mucosal integrity in response to noxious stimuli. To date, studies examining the roles of the NOS isoforms in experimental colitis have been conflicting, and the mechanisms by which these enzymes exert their effects remain unclear. To investigate and clarify the roles of the NOS isoforms in gut inflammation, we induced trinitrobenzenesulfonic acid colitis in eNOS, nNOS, and iNOS knockout (KO) mice, assessing the course of colitis at early and late times. Both eNOS and iNOS KO mice developed a more severe colitis compared with wild-type mice. During colitis, iNOS expression dramatically increased on epithelial and lamina propria mononuclear cells, whereas eNOS expression remained localized to endothelial cells. Electron and fluorescence microscopy identified bacteria in the ulcerated colonic mucosa of eNOS KO mice, but not in wild-type, iNOS, or nNOS KO mice. Furthermore, eNOS KO mice had fewer colonic goblet cells, impaired mucin production, and exhibited increased susceptibility to an inflammatory stimulus that was subthreshold to other mice. This susceptibility was reversible, because the NO donor isosorbide dinitrate normalized goblet cell numbers and ameliorated subsequent colitis in eNOS KO mice. These results identify a protective role for both iNOS and eNOS during colitis, with eNOS deficiency resulting in impaired intestinal defense against lumenal bacteria and increased susceptibility to coliti

Ulcerative colitis patients with an inflammatory response upon mesalazine cannot be desensitized: a randomized study

Background and aims. Mesalazine is a key drug in the treatment of ulcerative colitis (UC). Intolerance to mesalazine has been described, including fever and gastrointestinal symptoms. Several case reports reported successful desensitization of patients with mesalazine intolerance. The aim was to assess the number of UC patients who are persistently intolerant to mesalazine after single-blinded rechallenge and to test the effectiveness of a rapid desensitization protocol in UC patients demonstrated mesalazine intolerance. Methods. This is a prospective, singlie-blind randomized study in UC patients who discontinued mesalazine because of intolerance. Patients with severe reactions were excluded. Eligible patients underwent a skin patch test with mesalazine followed by a single-blinded randomized crossover rechallenge with 500 mg mesalazine or placebo. Patients with symptoms upon rechallenge were admitted to the hospital for 3 days oral desensitization. Results. Nine of the 37 identified UC patients who discontinued mesalazine because of intolerance were included. All nine patients had negative patch tests, seven patients had symptoms (fever, nausea, vomiting and diarrhea) within 2 h upon rechallenge. Four of these seven patients participated in the desensitization protocol and in none a successful desensitization could be performed. All four had an inflammatory intolerance reaction with rise in C-reactive protein. There were no elevations in serum tryptase or urinary-methylhistamine levels observed and no signs of immediate type allergic reactions, like urticaria, bronchial obstruction or anaphylaxis. Conclusion. We recommend not to rechallenge UC patients with an inflammatory response upon mesalazine and these patients will not benefit from a rapid desensitization protocol