Development and validity evidence of an objective structured assessment of technical skills score for minimally invasive linear-stapled, hand-sewn intestinal anastomoses: the A-OSATS score.

INTRODUCTION: The aim of this study was to develop a reliable objective structured assessment of technical skills (OSATS) score for linear-stapled, hand-sewn closure of enterotomy intestinal anastomoses (A-OSATS). MATERIALS AND METHODS: The Delphi methodology was used to create a traditional and weighted A-OSATS score highlighting the more important steps for patient outcomes according to an international expert consensus. Minimally invasive novices, intermediates, and experts were asked to perform a minimally invasive linear-stapled intestinal anastomosis with hand-sewn closure of the enterotomy in a live animal model either laparoscopically or robot-assisted. Video recordings were scored by two blinded raters assessing intrarater and interrater reliability and discriminative abilities between novices (n = 8), intermediates (n = 24), and experts (n = 8). RESULTS: The Delphi process included 18 international experts and was successfully completed after 4 rounds. A total of 4 relevant main steps as well as 15 substeps were identified and a definition of each substep was provided. A maximum of 75 points could be reached in the unweighted A-OSATS score and 170 points in the weighted A-OSATS score respectively. A total of 41 anastomoses were evaluated. Excellent intrarater (r = 0.807-0.988, p < 0.001) and interrater (intraclass correlation coefficient = 0.923-0.924, p < 0.001) reliability was demonstrated. Both versions of the A-OSATS correlated well with the general OSATS and discriminated between novices, intermediates, and experts defined by their OSATS global rating scale. CONCLUSION: With the weighted and unweighted A-OSATS score, we propose a new reliable standard to assess the creation of minimally invasive linear-stapled, hand-sewn anastomoses based on an international expert consensus. Validity evidence in live animal models is provided in this study. Future research should focus on assessing whether the weighted A-OSATS exceeds the predictive capabilities of patient outcomes of the unweighted A-OSATS and provide further validity evidence on using the score on different anastomotic techniques in humans.

Loci from a genome-wide analysis of bilirubin levels are associated with gallstone risk and composition.

BACKGROUND & AIMS: Genome-wide association studies have mapped loci that are associated with serum levels of bilirubin. Bilirubin is a major component of gallstones so we investigated whether these variants predict gallstone bilirubin content and overall risk for gallstones. METHODS: Loci that were identified in a meta-analysis to attain a genome-wide significance level of a P value less than 1.0×10(-7) (UGT1A1, SLCO1B1, LST-3TM12, SLCO1A2) were analyzed in 1018 individuals with known gallstone composition. Gallstone risk was analyzed in 2606 German choleystecomized individuals and 1121 controls and was replicated in 210 cases and 496 controls from South America. RESULTS: By using the presence of bilirubin as a phenotype, variants rs6742078 (UGT1A1; P = .003), rs4149056 (SLCO1B1; P = .003), and rs4149000 (SLCO1A2; P = .015) were associated with gallstone composition. In regression analyses, only UGT1A1 and SLCO1B1 were independently retained in the model. UGT1A1 (rs6742078; P = .018) was associated with overall gallstone risk. In a sex-stratified analysis, only male carriers of rs6742078 had an increased risk for gallstone disease (P = 2.1×10(-7); odds ratio(recessive), 2.34; P(women) = .47). The sex-specific association of rs6742078 was confirmed in samples from South America (P(men) = .046; odds ratio(recessive), 2.19; P(women) = .96). CONCLUSIONS: The UGT1A1 Gilbert syndrome variant rs6742078 is associated with gallstone disease in men; further studies are required regarding the sex-specific physiology of bilirubin and bile acid metabolism. Variants of ABCG8 and UGT1A1 are the 2 major risk factors for overall gallstone disease, they contribute a population attributable risk of 21.2% among men.

Assessment of anti-inflammatory tumor treatment efficacy by longitudinal monitoring employing sonographic micro morphology in a preclinical mouse model.

BACKGROUND: With the development of increasingly sophisticated three-dimensional volumetric imaging methods, tumor volume can serve as a robust and reproducible measurement of drug efficacy. Since the use of molecularly targeted agents in the clinic will almost certainly involve combinations with other therapeutic modalities, the use of volumetric determination can help to identify a dosing schedule of sequential combinations of cytostatic drugs resulting in long term control of tumor growth with minimal toxicity. The aim of this study is to assess high resolution sonography imaging for the in vivo monitoring of efficacy of Infliximab in pancreatic tumor. METHODS: In the first experiment, primary orthotopic pancreatic tumor growth was measured with Infliximab treatment. In the second experiment, orthotopic tumors were resected ten days after inoculation of tumor cells and tumor recurrence was measured following Infliximab treatment. Tumor progression was evaluated using 3D high resolution sonography. RESULTS: Sonography measurement of tumor volume in vivo showed inhibitory effect of Infliximab on primary tumor growth in both non-resected and resected models. Measurement of the dynamics of tumor growth by sonography revealed that in the primary tumor Infliximab is effective against established tumors while in the resection model, Infliximab is more effective at an early stage following tumor resection. Infliximab treatment is also effective in inhibiting tumor growth growth as a result of tumor cell contamination of the surgical field. CONCLUSIONS: Clinical application of Infliximab is feasible in both the neoadjuvant and adjuvant setting. Infliximab is also effective in slowing the growth of tumor growth under the peritoneum and may have application in treating peritoneal carcinomatosis. Finally the study demonstrates that high resolution sonography is a sensitive imaging modality for the measurement of pancreatic tumor growth.

Recurrence of gallstones after cholecystectomy is associated with ABCG5/8 genotype.

BACKGROUND: Gallstone disease is a frequent and economically highly relevant disorder, with cholecystectomy representing one of the most frequently performed operations world-wide. Gallstone recurrence after cholecystectomy is associated with complications such as biliary sepsis and pancreatitis. As yet, variant ABCG8-D19H is the most widely recognized genetic risk factor for gallstone disease. The aim of the study is to investigate whether ABCG8-D19H is associated with gallstone recurrence after cholecystectomy. METHODS: Two thousand three hundred and eight patients from an earlier study of gallstone risk factors were re-contacted by mail, leading to 1,915 patients with available clinical and genetic information. Symptomatic gallstone recurrence was established if it occurred more than six months after surgery. Median follow-up time after cholecystectomy was eight years. RESULTS: Gallstones recurred in 37 patients (1.9%). ABCG-D19H was found to be significantly associated with gallstone recurrence (p = 0.034). The allelic odds ratio was 1.97 (95% CI 1.12-∞). In a multivariate logistic regression analysis adjusted for age, sex, BMI and type of surgery, ABCG8-D19H remained a significant predictor, both in the total cohort (p = 0.024) and in the subgroup for whom information on type and scheduling of surgery was available (N = 1,650, p = 0.020). CONCLUSIONS: ABCG8-D19H is a predictor of gallstone recurrence, a major long term postoperative biliary complication. Moreover, the observed association also reemphasizes the importance of the sterolin transporter for stone formation.

Sunitinib (SU11248) inhibits growth of human ovarian cancer in xenografted mice.

BACKGROUND: Treatment of ovarian cancer is still challenging especially in recurrent platinum refractory cases. Sunitinib is a multi tyrosine kinase inhibitor targeting receptors for vascular endothelial growth factor and platelet-derived growth factor which play a role in tumor angiogenesis. It has been approved for the treatment of recurrent gastro intestinal stroma tumors and metastatic renal cancer. MATERIALS AND METHODS: In this study, sunitinib was tested for its effectiveness as a single agent in an ovarian cancer xenograft mouse model. Skov3 cells stably expressing firefly luciferase were injected into SCID beige mice. Mice received either 40 mg/kg bodyweight sunitinib or vehicle control. Tumor growth was monitored longitudinally by luciferase signal. RESULTS: Sunitinib significantly reduced tumor growth (p=0.0052) and peritoneal metastases, and was associated with a significantly reduced microvessel density count (p<0.001). CONCLUSION: These results suggest that clinical trials are warranted for the evaluation of sunitinib for treatment of patients with recurrent or advanced ovarian cancer.