Multi-institutional expert update on the use of laparoscopic bile duct exploration (LBDE) in the management of choledocholithiasis: lesson learned from 3950 procedures

Background: Recently there has been a growing interest in the laparoscopic management of common bile duct stones with gallbladder in situ (LBDE), which is favoring the expansion of this technique. Our study identified the standardization factors of LBDE and its implementation in the single-stage man agement of choledocholithiasis. Methods: A retrospective multi-institutional study among 17 centers with proven experience in LBDE was performed. A cross-sectional survey consisting of a semi-structured pretested questionnaire was distributed covering the main aspects on the use of LBDE in the management of choledocholithiasis. Results: A total of 3950 LBDEs were analyzed. The most frequent indication was jaundice (58.8%). LBDEs were performed after failed ERCP in 15.2%. The most common approach used was the transcystic (63.11%). The overall series failure rate of LBDE was 4% and the median rate for each center was 6% (IQR, 4.5-12.5). Median operative time ranged between 60-120 min (70.6%). Overall morbidity rate was 14.6%, with a postoperative bile leak and complications ≥3a rate of 4.5% and 2.5%, respectively. The operative time decreased with experience (P = .03) and length of hospital stay was longer in the presence of a biliary leak (P = .04). Current training of LBDE was defined as poor or very poor by 82.4%. Conclusion: Based on this multicenter survey, LBDE is a safe and effective ap proach when performed by experienced teams. The generalization of LBDE will be based on developing training programs

Ultrasonographic assessment of brachial artery reactivity as a predictor of adverse outcome in patients undergoing emergency laparotomy for perforated peritonitis – Prospective observational study

Background and Aims: This study aimed to assess if pre- and postoperative parameters of brachial artery reactivity (BAR), like flow-mediated dilation (FMD) and hyperaemic velocity (HV), could predict in-hospital mortality in perforation peritonitis patients undergoing emergency laparotomy. Methods: In this prospective observational study, adult patients with perforation peritonitis undergoing emergency laparotomy were recruited. FMD and HV were measured preoperatively, postoperatively and at 24 and 48 h post-surgery. Adult patients undergoing elective laparotomy served as the control group. The primary outcome was in-hospital mortality. Baseline and BAR parameters were compared between survivors and non-survivors. Risk factors for mortality were identified by univariate analysis. Prognostic performances of BAR parameters were assessed by different models using logistic regression. All statistical analyses were performed on STATA version 13 for Mac OS. Results: Seventy-six emergency laparotomy patients were recruited, and 26 died during the hospital stay. FMD and HV were comparable at all time points between survivors and non-survivors, except that HV was higher in survivors at 48 h post-surgery (median [interquartile range] 1.28 [1.16–1.49] vs. 1.16 [0.86–1.35], P = 0.010]. HV at 48 h predicted mortality (adjusted odds ratio [OR] [95% confidence interval] 21.05 [1.04–422.43], P = 0.046), and a model consisting of age, Acute Physiology and Chronic Health Evaluation (APACHE) score and HV at 48 h was the best predictor of mortality (area under the receiver operating characteristic (AUROC) curve 0.82). Conclusion: HV, as measured by ultrasonography of the brachial artery at 48 h postoperatively, is a good predictor of mortality in patients undergoing emergency laparotomy for perforation peritonitis

Autoacetylation of Purified Calreticulin Transacetylase Utilizing Acetoxycoumarin as the Acetyl Group Donor

Our earlier reports documented that calreticulin, a multifunctional Ca(2+)-binding protein in endoplasmic reticulum lumen, possessed protein acetyltransferase function termed Calreticulin Transacetylase (CRTAase). The autoacetylation of purified human placental CRTAase concomitant with the acetylation of receptor proteins by a model acetoxycoumarin, 7,8-Diacetoxy-4-methylcoumarin, was observed. Here, we have examined the autoacetylation property of CRTAase by immunoblotting and mass spectrometry. Ca(2+) was found to inhibit CRTAase activity. The inhibition of both autoacetylation of CRTAase as well as acetylation of the receptor protein was apparent when Ca(2+) was included in the reaction mixture as visualized by interaction with anti-acetyl lysine antibody. The acetylation of lysines residues: -48, -62, -64, -153, and -159 in N-domain and -206, -207, -209, and -238 in P-domain of CRTAase were located by high-performance liquid chromatography-electronspray ionization tandem mass spectrometry. Further, computer assisted protein structure modeling studies were undertaken to probe the effect of autoacetylation of CRTAase. Accordingly, the predicted CRTAase 3D model showed that all the loop regions of both N- and P-domain bear the acetylated lysines. Energy minimization of the acetylated residues revealed charge neutralization of lysines due to the N-epsilon-acetylation which may facilitate the interaction of CRTAase with the protein substrate and the subsequent transacetylase action

Normalization of deranged signal transduction in lymphocytes of COPD patients by the novel calcium channel blocker H-DHPM

Investigations on the role of intracellular Ca(2+) ion concentration in the mechanism of development of COPD in smokers and non-smokers were carried out. The intracellular Ca(2+) levels were found to be increased in human lymphocytes in patients with COPD as compared to non-smokers and smokers without COPD. The investigations reveal an association in altered intracellular Ca(2+) regulation in lymphocytes and severity of COPD, by means of significant activation of Protein kinase C and inducible nitric oxide synthase (iNOS). The effect of a novel calcium channel blocker ethyl 4-(4'-heptanoyloxyphenyl)-6-methyl-3,4-dihydropyrimidin-2-one-5-carboxylate (H-DHPM) as a potential candidate for the treatment of COPD was also investigated. H-DHPM treated cells showed a decrease in intracellular Ca(2+) level as compared to the control cells. Molecular studies were carried out to evaluate the expression profile of NOS isoforms in human lymphocytes and it was shown that H-DHPM decreases the increased iNOS in COPD along with reestablishing the normal levels of endothelial nitric oxide synthase (eNOS). The results of H-DHPM were comparable with those of Amlodipine, a known calcium channel blocker. Calcium channel blocker H-DHPM proves to be a potential candidate for the treatment of COPD and further clinical studies are required to prove its role in the treatment of pulmonary hypertension (PH). (C) 2011 Elsevier Masson SAS. All rights reserved

Multi-institutional expert update on the use of laparoscopic bile duct exploration in the management of choledocholithiasis: Lesson learned from 3950 procedures.

Recently there has been a growing interest in the laparoscopic management of common bile duct stones with gallbladder in situ (LBDE), which is favoring the expansion of this technique. Our study identified the standardization factors of LBDE and its implementation in the single-stage management of choledocholithiasis. A retrospective multi-institutional study among 17 centers with proven experience in LBDE was performed. A cross-sectional survey consisting of a semi-structured pretested questionnaire was distributed covering the main aspects on the use of LBDE in the management of choledocholithiasis. A total of 3950 LBDEs were analyzed. The most frequent indication was jaundice (58.8%). LBDEs were performed after failed ERCP in 15.2%. The most common approach used was the transcystic (63.11%). The overall series failure rate of LBDE was 4% and the median rate for each center was 6% (IQR, 4.5-12.5). Median operative time ranged between 60-120 min (70.6%). Overall morbidity rate was 14.6%, with a postoperative bile leak and complications ≥3a rate of 4.5% and 2.5%, respectively. The operative time decreased with experience (P = .03) and length of hospital stay was longer in the presence of a biliary leak (P = .04). Current training of LBDE was defined as poor or very poor by 82.4%. Based on this multicenter survey, LBDE is a safe and effective approach when performed by experienced teams. The generalization of LBDE will be based on developing training programs