Mind the Sump! - Diagnostic Challenge of a Rare Complication of Choledochoduodenostomy

Sump syndrome is a rare long-term complication of side-to-side choledochoduodenostomy (CDD), a common surgical procedure in patients with biliary tract disease in the era before endoscopic retrograde cholangiopancreatography (ERCP). Frequently only pneumobilia, serving as sign for functioning biliary-enteric anastomosis, is reminiscent of the former surgery. We present the case of an 81-year-old patient with sump syndrome who presented with clinical signs of ascending cholangitis, decades after the initial CDD procedure. Finally the detailed medical history that was taken very thoroughly in combination with the presence of pneumobilia led to the suspicion of sump syndrome. Sump syndrome was diagnosed by ERCP, and after endoscopic debris extraction and antibiotic treatment the patient recovered quickly. In the ERCP era little is known about CDD and its long-term complications, especially by young colleagues and trainees. Therefore this report provides an excellent opportunity to refresh the knowledge and raise awareness for this syndrome

Reconstructing signaling pathways from RNAi data using probabilistic Boolean threshold networks

Motivation: The reconstruction of signaling pathways from gene knockdown data is a novel research field enabled by developments in RNAi screening technology. However, while RNA interference is a powerful technique to identify genes related to a phenotype of interest, their placement in the corresponding pathways remains a challenging problem. Difficulties are aggravated if not all pathway components can be observed after each knockdown, but readouts are only available for a small subset. We are then facing the problem of reconstructing a network from incomplete data. Results: We infer pathway topologies from gene knockdown data using Bayesian networks with probabilistic Boolean threshold functions. To deal with the problem of underdetermined network parameters, we employ a Bayesian learning approach, in which we can integrate arbitrary prior information on the network under consideration. Missing observations are integrated out. We compute the exact likelihood function for smaller networks, and use an approximation to evaluate the likelihood for larger networks. The posterior distribution is evaluated using mode hopping Markov chain Monte Carlo. Distributions over topologies and parameters can then be used to design additional experiments. We evaluate our approach on a small artificial dataset, and present inference results on RNAi data from the Jak/Stat pathway in a human hepatoma cell line. Availability: Software is available on request. Contact

Differential prognostic significance of sarcopenia in metastatic esophageal squamous and adenocarcinoma.

BACKGROUND Sarcopenia indicates poor prognosis in various malignancies. We evaluated the association of sarcopenia with overall (OS) and progression-free survival (PFS) in metastatic esophageal cancer (MEC) patients, a population often presenting with poor nutritional status. METHODS In newly diagnosed MEC patients managed at the Princess Margaret (PM) Cancer Centre (diagnosed 2006-2015), total muscle area, visceral adiposity (VA), and subcutaneous adiposity (SA) were quantified on abdominal computed tomography at L3. Sarcopenia was determined using published cutoffs, based on sex and height. RESULTS Of 202 MEC patients, most were male (166/82%), < 65 years (116/57%), and had adenocarcinoma histology (141/70%); 110/54% had recurrent MEC after initial curative-intent treatment; 92/46% presented with de novo MEC. At stage IV diagnosis, 20/10% were underweight, 97/48% were normal-weight and 84/42% were overweight/obese; 103/51% were sarcopenic. Sarcopenia was associated with worse median OS (4.6 vs. 7.9 months; log-rank p = 0.03) and 1-year survival, even after adjusting for other body composition variables (e.g., BMI, VA, and SA): adjusted-HR 1.51 [95% CI 1.1-2.2, p = 0.02]. In post hoc analysis, sarcopenia was highly prognostic in adenocarcinomas (p = 0.003), but not squamous cell carcinomas (SCC). In patients receiving palliative systemic treatment (104/51%), sarcopenia was associated with shorter PFS (p = 0.004) in adenocarcinoma patients (75/72%). CONCLUSIONS In metastatic esophageal adenocarcinomas, sarcopenia is associated with worse PFS and OS. In metastatic esophageal SCC, there was a non-significant trend for worse PFS but no association with OS. In order to offset the poor prognosis associated with sarcopenia particularly in metastatic esophageal adenocarcinoma patients, future research should focus on possible countermeasures