Improved outcomes using a systematic and evidence-based approach to the laparoscopic Roux-en-Y gastric bypass in a single academic institution

No standardized approach exists for laparoscopic Roux-en-Y gastric bypass (LRYGB). At a newly instituted bariatric surgery program, four experienced laparoscopic surgeons used the systematic and evidence-based approach consisting of multidisciplinary preoperative evaluation, screening, and education; standardized operative technique; inpatient clinical pathway; and close postoperative follow-up. The outcomes were subsequently analyzed to determine if this approach improved the morbidity and mortality. From January 2003 to June 2006, 835 consecutive LRYGBs were performed. The patient population was 85 per cent women with a mean body mass index (BMI) of 50.4 kg/m2 (range 33-96 kg/m2). The mean age was 44 (range 15-67). Sixty-two per cent of the patients had previous abdominal or pelvic operations. The conversion rate to open surgery was 0.2 per cent. The average length of hospital stay was 2.6 days (range 2-13 days). There were no anastomotic leaks or deaths. The 30-day readmission and re-operation rates were 3.2 per cent and 1.8 per cent, respectively. The incidence of anastomotic stricture, marginal ulcer, bleeding, pulmonary embolism, and internal hernia was 0.8 per cent, 3.5 per cent, 4.2 per cent, 0.1 per cent, and 0.4 per cent, respectively. A systematic and evidence-based approach to the LRYGB by experienced laparoscopic surgeons resulted in a lower incidence of complications when compared with the published results from other comparable institutions.     

Rupture of membranes in second trimester of pregnancy

The management of rupture of membranes at a nearly viability stage is still controversial. A case of a primigravida, who had rupture of membranes at 23 weeks of gestation, is reported. On conservative management, her pregnancy continued to 30 weeks and she delivered a normal fetus, who showed no abnormality till one year of follow-up.     

Extraosseous bone formation in the renal pelvis

PURPOSE: We evaluated the frequency and features of extraosseous bone formation in the kidneys of patients undergoing percutaneous nephrolithotomy. MATERIALS AND METHODS: Percutaneous nephrolithotomy was performed in 621 patients at our institution between 1997 and 2006. In 21 cases metaplastic bone arising from the urothelium was observed. Clinical, radiographic and histopathological features of this group were studied in detail. RESULTS: Patient age ranged from 7 to 40 years (median 11). Extraosseous bone formation was identified in 7 right (33%) and 14 left (67%) kidneys. In all cases extraosseous bone was identified at the angle of the pelvis and ureter, just proximal to the ureteropelvic junction. The typical radiographic appearance of a radiopaque eccentric halo surrounding an area of lesser radiological density connected with the urothelium was seen in 10 of 13 radiographs (77%). Histopathological evaluation showed well formed trabecular bone with surface osteoblastic activity, areas of intratrabecular adipose bone marrow and hematopoietic cells in 5 cases (24%); woven bone intimately related to trabecular bone with scattered hematopoietic cells in 14 (67%); and entirely woven bone with associated mineral deposits and prominent fibroblastic proliferation in 2 (10%). CONCLUSIONS: Although rarely reported in the literature, metaplastic bone formation in the renal pelvis was seen relatively frequently in our patient population. The pathogenesis of this phenomenon is not clearly understood. Recognition of extraosseous bone is important, since it has implications for management and prognosis. In-depth studies of this phenomenon are required to arrive at any conclusions regarding its etiology.     

Prediction of solvation sites at the interface of Src SH2 domain complexes using molecular dynamics simulations

Src Homology 2 (SH2) domains are approximately 100 amino acid domains that mediate recognition of tyrosine-phosphorylated sites by signalling proteins. Structures of SH2 domains with bound ligands indicate a potentially important role of water in influencing the binding thermodynamics. In this study, we used molecular dynamics (MD) simulation methods to evaluate solvation sites at the binding interface of the Src SH2 domain. We designed a software, WaRP (Water Residency Potential), to compute the positions of hydration sites from coordinates data of MD simulations and studied the impact of the computed positions on the prediction of the thermodynamics of Src SH2 domain binding to phosphorylated peptides using a method based on accessible surface area buried upon association. Two dually phosphorylated ligands and one monophosphorylated ligand were studied. We showed that the software predicted between 70% and 85% of the crystallographic water molecules depending on complexes. Comparison of the predicted water structures of both the bound and unbound binding partners led to a thorough evaluation of water behaviour during the binding reaction. We also showed that the predicted water structures of all ligand-SH2 domain structures investigated may be used to derive the entropy change provided that the heat capacity change is known. This study is the first to examine the dynamics of the water structure around the SH2 domain binding interface and contributes to our understanding of binding thermodynamics in SH2 domains.     

Six1 overexpression in ovarian carcinoma causes resistance to TRAIL-mediated apoptosis and is associated with poor survival

Tumorigenesis can arise from inappropriate activation of developmental genes in mature tissues. Here, we show that the developmental regulator Six1 is overexpressed in ovarian carcinoma cell lines (OCC) compared with normal ovarian surface epithelium. As observed in other cancers, Six1 overexpression in OCC leads to increased A-type cyclin expression and increased proliferation. In addition, Six1 overexpression renders OCC resistant to tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis, and Six1 knockdown in the TRAIL-resistant SKOV3 ovarian carcinoma line dramatically sensitizes the cells to TRAIL. Because inactivation of the TRAIL response has been linked to metastasis, and because antibodies and recombinant ligand that activate the TRAIL pathway are currently in clinical trials against ovarian carcinoma, we screened normal ovarian and carcinoma specimens for Six1 mRNA. Six1 was overexpressed in 50% of the early-stage (stage I) and 63% of the late-stage (stages II, III, and IV) ovarian carcinomas examined, with late-stage carcinomas expressing approximately 3-fold higher Six1 mRNA levels on average compared with early-stage tumors. Importantly, in patients with late-stage disease, high Six1 expression was associated with significantly shortened survival (P = 0.0015). These data suggest that Six1 may contribute to ovarian epithelial carcinogenesis by simultaneously increasing proliferation and decreasing TRAIL-mediated apoptosis and imply that Six1 may be an important determinant of TRAIL therapy response that should be considered in patient selection for TRAIL-related clinical trials.