Fecal continence outcomes are associated with the type, height, and stage procedure of ileal pouch-anal anastomosis

Purpose This study aims to analyze the quality of life in patients with an ileal pouch-anal anastomosis (IPAA) and to investigate the association between height and type of the anastomosis, the number of stage procedures and age, and the fecal continence outcomes. Methods This is a cross-sectional retrospective study in patients who had undergone IPAA between 1992 and 2016 (N = 133). We sent questionnaires to 102 eligible patients (64% response rate). We used the Wexner score to assess fecal incontinence: 0 = no incontinence to 20 = complete incontinence. We used RAND-36 to measure quality of life. Results Patients who underwent mucosectomy with hand-sewn anastomoses (n = 11, 17%) had significantly higher median Wexner scores than patients with stapled anastomoses (10 versus 3, P = 0.003). Lower anastomoses correlated significantly with increasing Wexner scores (r = - 0.468, P <0.001). Quality of life of incontinent patients was diminished. Patients who were older at the time of IPAA surgery had higher Wexner scores (P = 0.004), while the time between surgery and questionnaire did not influence their Wexner scores (P = 0.810). Considering the stage procedures, multiple linear regression showed that the two-stage procedure without diverting ileostomy was significantly associated with higher Wexner scores (B = 0.815, P = 0.02), adjusted for sex (P = 0.008) and anastomosis type (P = 0.002). The three-stage procedure showed equally low complications and anastomotic leakage rates. Conclusion Mucosectomy with more distal, hand-sewn anastomosis and increasing age at IPAA surgery was associated with poorer fecal continence outcomes. The three-stage procedure appears to give the best fecal continence results without increasing complications. Furthermore, incontinence reduced patient's quality of life

Transcriptomic characterization of culture-associated changes in murine and human precision-cut tissue slices

Our knowledge of complex pathological mechanisms underlying organ fibrosis is predominantly derived from animal studies. However, relevance of animal models for human disease is limited; therefore, an ex vivo model of human precision-cut tissue slices (PCTS) might become an indispensable tool in fibrosis research and drug development by bridging the animal-human translational gap. This study, presented as two parts, provides comprehensive characterization of the dynamic transcriptional changes in PCTS during culture by RNA sequencing. Part I investigates the differences in culture-induced responses in murine and human PCTS derived from healthy liver, kidney and gut. Part II delineates the molecular processes in cultured human PCTS generated from diseased liver, kidney and ileum. We demonstrated that culture was associated with extensive transcriptional changes and impacted PCTS in a universal way across the organs and two species by triggering an inflammatory response and fibrosis-related extracellular matrix (ECM) remodelling. All PCTS shared mRNA upregulation of IL-11 and ECM-degrading enzymes MMP3 and MMP10. Slice preparation and culturing activated numerous pathways across all PCTS, especially those involved in inflammation (IL-6, IL-8 and HMGB1 signalling) and tissue remodelling (osteoarthritis pathway and integrin signalling). Despite the converging effects of culture, PCTS display species-, organ- and pathology-specific differences in the regulation of genes and canonical pathways. The underlying pathology in human diseased PCTS endures and influences biological processes like cytokine release. Our study reinforces the use of PCTS as an ex vivo fibrosis model and supports future studies towards its validation as a preclinical tool for drug development

Laparoscopic resection of a residual retroperitoneal tumor mass of nonseminomatous testicular germ cell tumors

Resection of a residual retroperitoneal tumor mass (RRRTM) is standard procedure after combination chemotherapy for metastatic nonseminomatous testicular germ cell tumors (NSTGCT). At the University Medical Center Groningen, 79 consecutive patients with disseminated NSTGCT were treated with cisplatin combination chemotherapy between 2005 and 2007. Laparoscopic RRRTM was performed for patients with RRTM located less than 5 cm ventrally or laterally from the aorta or the vena cava. The 29 patients who fulfilled the criteria had a median age of 25 years (range, 16-59 years). The stages of disease before chemotherapy treatment according to the Royal Marsden classification were 2A (n = 6, 21%), 2B (n = 14, 48%), 2C (n = 3, 10%), and 4 with a lymph node status of N2 (n = 6, 21%). The median duration of laparoscopy was 198 min (range, 122-325 min). The median diameter of the RRTM was 21 mm (range, 11-47 mm). Laparoscopic resection was successful for 25 patients (86%). Conversion was necessary for three patients (10%): two due to bleeding and one because of obesity. One nonplanned hand-assisted procedure (3%) also had to be performed. Histologic examination of the specimens showed fibrosis or necrosis in 12 patients (41%), mature teratoma in 16 patients (55%), and viable tumor in 1 patient (3%). The median hospital stay was 1 day (range, 1-6 days). During a median follow-up period of 47 months (29-70 months), one patient experienced an early relapse (1 month after the end of treatment) (4%). For properly selected patients, laparoscopic resection of RRTM is an improvement in the combined treatment of disseminated NSTGCT and associated with a short hospital stay, minimal morbidity, rapid recovery, and a neat cosmetic result. Long-term data to prove oncologic efficacy are awaited

Outcome of pancreas transplantation from donation after circulatory death compared to donation after brain death

Introduction: To overcome the gap of organ shortage grafts from donation after circulatory death (DCD) can be used. This review evaluates the outcomes after DCD pancreas donation compared to donation after brain death (DBD). Materials and methods: A literature search was performed using Medline, Embase, and PubMed databases. All comparative cohort studies reporting the outcome after DCD and DBD pancreas transplantation were included. All data were assessed according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. To evaluate the event rates, pooled odds ratios (ORs) as well as the 95% confidence intervals (CI) were calculated. Since the number of studies is small we used the random effects model only to overcome heterogeneity. Results: There is no difference in 1-year pancreas graft survival (OR 1.092, CI 95% 0.649-1.837, P = 0.741) or patient survival (OR 0.699, CI 95% 0.246-1.985, P = 0.502). Simultaneous pancreas-kidney (SPK) transplantation showed significantly higher graft survival rates compared to pancreas transplantation alone (87.2% vs. 76.6%, P <0.001 in DBD and 86.5% vs. 74.9%, P <0.001 in DCD). DCD SPK grafts show a higher delayed kidney graft function rate compared to DBD SPK-grafts (OR 0.209, CI 95% 0.104-0.421, P <0.001). There is significantly less pancreas graft thrombosis after DBD-donation (OR 0.567, CI 95% 0.340-0.946, P = 0.030). We found no difference in the HbA1c level at 1-year follow-up with a median of 5.4% in both groups and a mean of 5.63% (DCD) vs 5.43% (DBD). Discussion: DCD pancreas transplantation has comparable patient and 1-year graft survival rates and should be considered a safe alternative for DBD pancreas transplantation. (C) 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved

Regional Differences in Intestinal Drug Metabolism

The intestines are key for the absorption of nutrients and water as well as drug metabolism, and it is well known that there are clear differences in the expression profile of drug metabolism enzymes along the intestinal tract. Yet, only a few studies have thoroughly investigated regional differences in human intestinal drug metabolism. In this study, we evaluated phase I and phase II metabolism in matched human ileum and colon precision-cut intestinal slices (PCIS). To this end, human PCIS were incubated for 3 h with testosterone (TT) and 7-hydroxycoumarin (7-HC) to examine phase I and phase II metabolism, respectively. Metabolite formation was assessed by high-performance liquid chromatography (HPLC) analysis. Our results demonstrated that androstenedione, 6β-hydroxytestosterone, 2β-hydroxytestosterone, and 7-HC sulfate, were predominantly formed in the ileum, while 15α-hydroxytestosterone and 7-HC glucuronide were mainly produced in the colon. Moreover, we also observed sex differences in phase II metabolite formation, which appeared to be higher in males as compared to females. Taken together, we demonstrated that phase I metabolism predominantly occurs in ileum PCIS, while phase II metabolism mostly takes place in colon PCIS. Moreover, we revealed that human PCIS can be used to study both regional and sex differences in intestinal metabolism