Search

Background: Prolonged operative time is a well-known risk factor for surgical site infections (SSI). There remains limited literature regarding correlates of SSIs specific for general surgery procedures of longer duration. This study aims to identify potential risk factors of SSIs for colorectal and hepatobiliary surgeries of prolonged duration. Methods: A retrospective chart review was performed for elective colorectal and hepatobiliary procedures of prolonged operative duration (≥ 4 hours) from 2008-2011 at Sunnybrook Health Sciences Centre. Patient and procedural characteristics and compliance with local guidelines for main SSI prevention practices were evaluated. Multivariate analysis was performed to identify independent risk factors of SSI development. Results: There were 547 patients with operations ≥ 4 hours and 57 (10%) SSI cases - 43 (75%) deep/ superficial and 14 (25%) organ/space. Average age was 62, BMI 27.3, weight 77.1 kg, and operative time 366 minutes. Less than 40% of all patients received intra-operative antibiotic prophylaxis measures in accordance with local guidelines. Multivariate logistic regression identified operative time (OR 1.22, 95% CI = 1.09-1.36, P < 0.001) as associated with the development of SSIs. Multivariate analysis demonstrated a non-significant association for increasing odds of SSIs when intra-operative antibiotic re-dosing was not in accordance with local guidelines (OR 1.54, 95% CI = 0.82-2.89, P=0.177). Conclusions: Healthcare providers should anticipate a greater likelihood for SSIs following lengthy operations regardless of patient characteristics or procedural factors. There is a need to target the improvement of antibiotic re-dosing practices as a means to decrease SSIs. [ABSTRACT FROM AUTHOR]

Secure reconstruction of multiple hepatic ducts severely damaged by tumor invasion or iatrogenic injury is very difficult. If percutaneous or endoscopic biliary stenting fails, one or more percutaneous transhepatic biliary drainage (PTBD) tubes must be maintained in place for the rest of the patient's life. To cope with such difficult situations, we present a surgical technique termed cluster hepaticojejunostomy (HJ), which can be coupled with palliative bile duct resection. The cluster HJ technique consisted of applying multiple internal biliary stents and a single wide porto-enterostomy to surrounding connective tissues. We present a preliminary study with six patients. Five perihilar cholangiocarcinoma patients undergoing palliative bile duct resection received this procedure. Follow-up PTBD tubogram and hepatobiliary scintigraphy were performed at 1-2 weeks after surgery, after which the PTBD tubes were removed. No patient showed surgical complications, and the 6-month patency rate of clustered HJ was 80 %. Another patient with laparoscopic cholecystectomy-associated major bile duct injury showed no biliary complications in the 5-year period following this procedure. Based on the results of this study, the cluster HJ technique may be a useful surgical method enabling the secure reconstruction of severely damaged hilar bile ducts. [ABSTRACT FROM AUTHOR]

Objective The aim of our study was to assess the complications of hepatic fibrosis associated with bile duct ligation and the potential curative role of sepia ink extract in hepatic damage induced by bile duct ligation. Methods Rattus norv egicus rats were divided into 3 groups: Sham-operated group, model rats that underwent common bile duct ligation (BDL), and BDL rats treated orally with sepia ink extract (200 mg/kg body weight) for 7, 14, and 28 d after BDL. Results There was a significant reduction in hepatic enzymes, ALP, GGT, bilirubin levels, and oxidative stress in the BDL group after treatment with sepia ink extract. Collagen deposition reduced after sepia ink extract treatment as compared to BDL groups, suggesting that the liver was repaired. Histopathological examination of liver treated with sepia ink extract showed moderate degeneration in the hepatic architecture and mild degeneration in hepatocytes as compared to BDL groups. Conclusion Sepia ink extract provides a curative effect and an antioxidant capacity on BDL rats and could ameliorate the complications of liver cholestasis. [ABSTRACT FROM AUTHOR]

Liver fibrosis is linked to VEGF-induced angiogenesis. Overexpression of exogenous vasohibin-1, a feedback inhibitor of angiogenesis, has been reported to reduce liver fibrosis after bile duct ligation (BDL). To uncover the function of endogenous vasohibin-1, we performed BDL using vasohibin-1-deficient mice and analyzed liver fibrosis, injury, and angiogenesis. Liver fibrosis was induced by 14-days of BDL in both wild-type and vasohibin-1-deficient mice. The liver sections were stained with anti-CD31 to visualize endothelial cells and with Sirius red to observe fibrotic regions. Total RNAs were purified from the livers and expression of collagen I α1 mRNA was measured by quantitative PCR. Plasma ALT activity was determined to assess liver injury. Surprisingly, the same extents of increases were seen in anti-CD31 and Sirius red stainings, collagen I α1 mRNA expressions, hepatic hydroxyproline contents, and ALT activity after 14-days of BDL in both wild-type and vasohibin-1-deficient mice. There was unexpectedly no difference between these mice, suggesting that anti-fibrogenic and angiogenic activities of the endogenous vasohibin-1 might be masked in the normal liver at early stage of hepatic fibrosis in mice. [ABSTRACT FROM AUTHOR]

Purpose: Prognostic indicators for distal cholangiocarcinoma have not been widely confirmed because of its rarity. Despite the early appearance of symptoms, it has a very poor prognosis. The aim of this study was to identify prognostic factors in patients undergoing pancreaticoduodenectomy (PD) for distal bile duct cancer (DBDC) in a high-volume center for pancreatic disease. Methods: From January 2000 to December 2013, 1490 PD were performed for periampullary disease. Data from all patients with histologically proven cholangiocarcinoma were reviewed. Preoperative data, post-operative complications, pathologic features, and survival were investigated. Results: Among 50 histologically proven DBDC (3.3 %), 4 patients who underwent CBD resection were excluded. Thus, the study population consisted of 46 patients. Overall surgical morbidity rate was 67.4 %; mortality was nil. Major complications were pancreatic fistula (47.8 %), abdominal collections (34.8 %), post-pancreatectomy hemorrhage (21.7 %), and delayed gastric emptying (10.9 %). The majority of resections were R0 (73.9 %). The presence of metastatic lymph nodes (N1) was identified in 76.1 % of cases. Among N1 cases, the most frequently involved lymph nodes were pancreaticoduodenal nodes (50 %), hepatoduodenal ligament nodes (21.7 %), superior mesenteric artery nodes (8.7 %), and anterior hepatic artery nodes (4.3 %). Overall, survival rates were 88.8, 40, and 18 % at 1, 3, and 5 years, respectively. Median survival was 31 months. By univariate analysis, only tumor grading and nodal metastasis were predictors of poor prognosis ( p < 0.05). These findings were not confirmed in multivariate analysis. Conclusions: This study shows that DBDC is a rare entity even if large surgical series are reviewed. Tumor differentiation and nodal status have been confirmed as important prognostic factors. Pancreaticoduodenectomy remains the procedure of choice in order to obtain free surgical margins and in order to harvest the correct number of lymph nodes for a correct staging. [ABSTRACT FROM AUTHOR]

Background One-stage laparoscopic cholecystectomy and endoscopic retrograde cholangiopancreaticography (ERCP-LC) was compared with one-stage laparoscopic cholecystectomy and laparoscopic exploration of common bile duct (LC- LCBDE) in patients with choledocholithiasis in an attempt to fi nd the best mini-invasive treatment for choledocholithiasis. Patients and methods For this study, 46 patients with cholelithiasis and choledocholithiasis diagnosed with preoperative ultrasonography and other diagnostic studies were divided randomly into an ERCP-LC group (group A) (23 cases) and an LC-LCBDE group (group B) (23 cases). The surgical time, surgical success rate, postoperative complications, retained common bile duct stones, postoperative length of stay, and hospital charges for operative procedures were compared prospectively. Results There were no statistically signifi cant differences between the two groups in terms of surgical time, surgical success rate, postoperative complications, retained common bile duct stones, and postoperative length of stay, but there was a big difference in hospital charges for operative procedures. Conclusion Finally, we can conclude that there was no statistically signifi cant difference between the two groups in terms of surgical time, surgical success rate, postoperative complications, mortality rates, retained common bile duct stones, and postoperative length of stay. However, patients in group A were more vulnerable than patients in group B to developing low-grade cholangitis because of sphincterotomy performed during stone extraction. [ABSTRACT FROM AUTHOR]

Background: Prophylactic combined extrahepatic bile duct resection remains controversial for locally advanced gallbladder carcinoma without extrahepatic bile duct invasion. The aim of this study is to resolve this issue and establish an appropriate surgery for locally advanced gallbladder carcinoma. Methods: A total of 52 patients underwent surgical resection combined with extrahepatic bile duct resection for locally advanced gallbladder carcinoma without extrahepatic bile duct invasion, and their medical records were retrospectively reviewed for microvessel invasion (MVI), including lymphatic, venous, and/or perineural invasions, around the extrahepatic bile duct. Results: Of the 52 patients, 8 (15 %) had MVI around the extrahepatic bile duct. All of the 8 patients had Stage IV disease. According to a survival analysis of the 50 patients who tolerated surgery, MVIs around the extrahepatic bile duct and distant metastasis were identified as independent prognostic factors. Survival for patients with MVI around the extrahepatic bile duct was dismal, with a lack of 2-year survivors. Conclusions: MVI around the extrahepatic bile duct is a sign of extremely locally advanced gallbladder carcinoma; therefore, prophylactic combined bile duct resection has no survival impact for patients without extrahepatic bile duct invasion. [ABSTRACT FROM AUTHOR]

Background/aim: To investigate the efficacy of diffusion-weighted magnetic resonance imaging (DWI) in the diagnosis and staging of fibrosis induced by experimental bile duct ligation (BDL). Materials and methods: Twenty-four rats were divided randomly into four groups: control, BDL - 3 days, BDL - 2 weeks, and BDL - 4 weeks. DWI was performed with b-values of 100 and 500 on the rats from control group at day zero, on the rats from the BDL - 3 days group at the end of day 3, on the rats from the BDL - 2 weeks group at the end of day 14, and on the rats from the BDL - 4 weeks at the end of day 28. Results: When fibrosis scores generated in all groups were evaluated together, a strong negative correlation was detected between fibrosis scores and apparent diffusion coefficient (ADC) values measured using b 100 and b 500. ADC values obtained using b 100 were found to be significantly higher compared to the fibrosis observed in both the BDL - 2 weeks and BDL - 4 weeks groups (P < 0.003 and P < 0.001, respectively). Conclusion: We think that DWI may be an alternative to liver biopsy for the diagnosis and staging of hepatic fibrosis with underlying extrahepatic cholestasis. [ABSTRACT FROM AUTHOR]

Background: Endoscopic sphincterotomy (EST) is the standard treatment for biliary duct stones. However, performing additional cholecystectomy after EST is controversial. In this study, we aimed to evaluate the effects of cholecystectomy after EST. Methods: Between December 2008 and July 2011, we performed a prospective, randomized, single-center trial in 90 patients with proven gallstones who underwent EST and stone extraction. After the procedure, patients were randomly allocated to undergo cholecystectomy ( n = 45) or to the group of GB left in situ ( n = 45). The primary outcome was biliary complications at follow-up. Results: Cholecystectomy was performed in 26 patients (60.5 %) in cholecystectomy group and in 13 patients (28.9 %) in intended conservative group. The median follow-up was 41 months. An intention-to-treat analysis showed that 8 patients (18.6 %) in the cholecystectomy group and 9 (20.0 %) in those who had their GB left in situ had recurrent biliary events (Kaplan-Meier curve, Breslow test, p = 0.555). In an as-treated analysis, 4 patients (10.3 %) who underwent cholecystectomy and 13 patients (26.5 %) who did not undergo cholecystectomy had additional biliary events during the follow-up period (Log-rank, p = 0.037). However, additional biliary events of cholangitis were similar in the two groups, except for a case of cholecystitis (Log-rank, p = 0.998). Conclusions: Cholecystectomy after EST for biliary duct stones fails to reduce additional recurrent cholangitis but reduces additional cholecystitis. [ABSTRACT FROM AUTHOR]

Background: Major hepatectomy with extrahepatic bile duct resection for perihilar cholangiocarcinoma remains a highly morbid procedure. The association between preoperative sarcopenia and postoperative morbidity/mortality has been reported for various types of surgeries. The objective was to analyze the relationship between preoperative sarcopenia and postoperative morbidity/mortality in patients who underwent major hepatectomy with extrahepatic bile duct resection. Methods: This study included 256 patients who underwent major hepatectomy with extrahepatic bile duct resection from 2008 to 2014. Preoperative sarcopenia was assessed by a measurement of the total psoas muscle area (TPA). The measured TPA was normalized by height. Preoperative sarcopenia was defined as the presence of a normalized TPA in the lowest sex-specific tertile. Results: A total of 54 males and 31 females were determined to have preoperative sarcopenia. The length of the postoperative hospital stay for patients with sarcopenia was significantly longer than for those without sarcopenia (39 vs 30 days, p < 0.001). Patients with sarcopenia experienced a significantly higher rate of liver failure (ISGLS grade ≥ B) (33 vs 16 %), major complications with Clavien grade ≥ 3 (54 vs 37 %), and intra-abdominal abscess (29 vs 18 %) than those without sarcopenia (all p < 0.05). After a multivariate analysis, low normalized TPA (male <567 mm/m; female <395 mm/m) was identified as an independent risk factor for the development of liver failure (odds ratio 2.46). Conclusions: This study demonstrated that preoperative sarcopenia increased the morbidity rate including the rate of liver failure, in patients who underwent major hepatectomy with extrahepatic bile duct resection. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the prognostic value of F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with ampullary adenocarcinoma (AAC) after curative surgical resection. Methods: Fifty-two patients with AAC who had undergone F-FDG PET/CT and subsequent curative resections were retrospectively enrolled. The maximum standardized uptake value (SUV) and tumor to background ratio (TBR) were measured on F-FDG PET/CT in all patients. The prognostic significances of PET/CT parameters and clinicopathologic factors for recurrence-free survival (RFS) and overall survival (OS) were evaluated by univariate and multivariate analyses. Results: Of the 52 patients, 19 (36.5 %) experienced tumor recurrence during the follow-up period and 18 (35.8 %) died. The 3-year RFS and OS were 62.3 and 61.5 %, respectively. Preoperative CA19-9 level, tumor differentiation, presence of lymph node metastasis, SUV, and TBR were significant prognostic factors for both RFS and OS ( p < 0.05) on univariate analyses, and patient age showed significance only for predicting RFS ( p < 0.05). On multivariate analyses, SUV and TBR were independent prognostic factors for RFS, and tumor differentiation, SUV, and TBR were independent prognostic factors for OS. Conclusion: SUV and TBR on preoperative F-FDG PET/CT are independent prognostic factors for predicting RFS and OS in patients with AAC; patients with high SUV (>4.80) or TBR (>1.75) had poor survival outcomes. The role of and indications for adjuvant therapy after curative resection of AAC are still unclear. F-FDG uptake in the primary tumor could provide additive prognostic information for the decision-making process regarding adjuvant therapy. [ABSTRACT FROM AUTHOR]

Background: The long-term impact of transfusions with packed red blood cells (PRBC) among patients undergoing hepatopancreaticobiliary (HPB) surgery remains ill-defined. We sought to determine the impact of overall blood utilization, as well as a restrictive transfusion strategy, on long-term outcomes among patients undergoing an HPB resection for a malignancy. Methods: Data on overall blood utilization and hemoglobin (Hb) levels that triggered a transfusion were obtained for patients with cancer undergoing pancreas or liver surgery between 2009 and 2013. Risk-adjusted recurrence-free (RFS) and overall survival (OS) were assessed based on receipt of PRBC and whether the patient received a transfusion using a restrictive transfusion strategy (intraoperative: Hb <10 g/dL; postoperative: Hb <8 g/dL). Results: Four hundred forty-two patients underwent either a pancreas (58.1 %) or liver (41.9 %) resection. Most tumors were pancreatic in origin (41.8 %), while a subset were primary (23.1 %) or secondary (18.8 %) liver tumors. One hundred seventy-five (39.6 %) patients received ≥1 PRBC transfusion either intraoperatively (16.7 %), postoperatively (12.7 %), or both (10.2 %). There was a higher incidence of PRBC transfusion among patients undergoing a pancreas resection, those with higher comorbidities, and those with lower preoperative Hb levels. Perioperative morbidity was higher among patients receiving either 1-2 units (OR 3.14) or 3 or more units of PRBC (OR 8.54). Median OS was 31.9 months. Receipt of a blood transfusion was associated with a worse OS (1-2 units: HR 1.76; 3 + units: HR 2.50; both P < 0.05), and RFS (3 + units: HR 2.91; P = 0.02). Utilization of a restrictive transfusion strategy did not impact perioperative morbidity or long-term RFS or OS. Conclusions: Adoption of a more restrictive transfusion strategy in patients undergoing resection for cancer may preserve a limited resource, reduce costs, as well as avoid exposing oncology patients to the unnecessary risks associated with a transfusion. [ABSTRACT FROM AUTHOR]

Introduction: It is well supported in the literature that laparoscopic common bile duct exploration (LCBDE) for choledocholithiasis has equal efficacy when compared to ERCP followed by laparoscopic cholecystectomy. Decompression after supra-duodenal choledochotomy is common practice as it reduced the risk of bile leaks. We conducted a prospective non-randomized study to compare outcomes and length of stay in patients undergoing biliary stent insertion versus T-tube drainage following LCBDE via choledochotomy. Methods and procedures: The study involved 116 patients with choledocholithiasis who underwent LCBDE and decompression of the biliary system by either ante-grade biliary stent or T-tube insertion. A 7 French straight/duodenal curve biliary Diagmed™ stent (9-11 cm) was placed in 82 patients (Biliary Stent Group). T-tube insertion was used for 34 patients (T-tube group). The length of hospital stay and complications for the selected patients were recorded. All trans-cystic common bile duct explorations were excluded from the study. Results: The mean hospital stay for patients who underwent ante-grade biliary stent or T-tube insertion after LBCDE were 1 and 3.4 days, respectively. This is a statistically significant result with a p value of less than 0.001. Of the T-tube group, two patients required laparoscopic washout due to bile leaks, one had ongoing biliary stasis and one reported ongoing pain whilst the T-tube was in situ. A complication rate of 11.2 %, this was a significant finding. There were no complications or concerns reported for the Biliary Stent Group. Conclusion: Our results show that there is a significant reduction in length of hospital stay and morbidity for patients that have ante-grade biliary stent decompression of the CBD post laparoscopic choledochotomy when compared T-tube drainage. This implies that ante-grade biliary stent insertion is likely to reduce costs and increase overall patient satisfaction. We support the use of ante-grade biliary stent insertion during LCBDE when primary closure is not preferred. [ABSTRACT FROM AUTHOR]

Background/Aims: Endoscopic retrograde cholangiopancreatography (ERCP) can be an effective treatment for bile leakage after liver transplantation. We evaluated the efficacy of endoscopic treatment in liver transplantation in patients who developed bile leaks. Methods: Forty-two patients who developed bile leaks after liver transplantation were included in the study. If a bile leak was observed on ERCP, a sphincterotomy was performed, and a nasobiliary catheter was then inserted. If a bile leak was accompanied by a bile duct stricture, either the stricture was dilated with balloons, followed by nasobiliary catheter insertion across the bile duct stricture, or endoscopic retrograde biliary drainage was performed. Results: In the bile leakage alone group (22 patients), endoscopic treatment was technically successful in 19 (86.4%) and clinically successful in 17 (77.3%) cases. Among the 20 patients with bile leaks with bile duct strictures, endoscopic treatment was technically successful in 13 (65.0%) and clinically successful in 10 (50.0%) cases. Among the 42 patients who underwent ERCP, technical success was achieved in 32 (76.2%) cases and clinical success was achieved in 27 (64.3%) cases. Conclusions: ERCP is an effective and safe therapeutic modality for bile leaks after liver transplantation. ERCP should be considered as an initial therapeutic modality in post-liver transplantation patients. [ABSTRACT FROM AUTHOR]

Cholestatic liver fibrosis was achieved by bile duct ligation (BDL) in mice. Liver injury associated with BDL for 15 days included significant reactive oxygen/nitrogen species generation, liver inflammation, cell death and fibrosis. Administration of Epigallocatechin 3-Gallate (EGCG) in animals reduced liver fibrosis involving parenchymal cells in BDL model. EGCG attenuated BDL-induced gene expression of pro-fibrotic markers (Collagen, Fibronectin, alpha 2 smooth muscle actin or SMA and connective tissue growth factor or CTGF), mitochondrial oxidative stress, cell death marker (DNA fragmentation and PARP activity), NFκB activity and pro-inflammatory cytokines (TNFα, MIP1α, IL1β, and MIP2). EGCG also improved BDL induced damages of mitochondrial electron transport chain complexes and antioxidant defense enzymes such as glutathione peroxidase and manganese superoxide dismutase. EGCG also attenuated hydrogen peroxide induced cell death in hepatocytes in vitro and alleviate stellate cells mediated fibrosis through TIMP1, SMA, Collagen 1 and Fibronectin in vitro. In conclusion, the reactive oxygen/nitrogen species generated from mitochondria plays critical pathogenetic role in the progression of liver inflammation and fibrosis and this study indicate that EGCG might be beneficial for reducing liver inflammation and fibrosis. [ABSTRACT FROM AUTHOR]

Background & Aims Luteolin has been reported to exert antifibrogenic effects in CCl4-induced hepatic fibrosis in mice. However, limited information is available on the cellular and molecular events responsible for this effect. This study focused on the action of luteolin on hepatic stellate cells ( HSCs) and the relevant signalling molecules and pathways as well as the antifibrotic efficacy in multiple models of fibrosis. Methods The in vitro effect of luteolin on rat HSCs and HSC-T6 cells was assessed using proliferation assays, invasion chamber, quantitative real-time PCR analysis and Western blotting. The in vivo effect of luteolin on progression of fibrosis was assessed in three experimental rat models induced by CCl4, dimethylnitrosamine ( DMN) and bile duct ligation ( BDL). Results Luteolin inhibited proliferation, migration, collagen synthesis as well as expression of fibrosis-related genes in the activated HSCs and HSC-T6 cells stimulated with or without transforming growth factor-β1( TGFβ1) or platelet-derived growth factor ( PDGF). Luteolin induced HSC apoptosis associated with the increased caspase 3 activity and p53 expression, and induced G1 arrest with the decreased expression of bcl-2, Cyclin E and p-Cdk-2. Moreover, luteolin significantly inhibited PDGF and TGFβ1-simulated phosphorylation of AKT and Smad pathway. In vivo study showed that luteolin administration markedly alleviated hepatic fibrosis along with reduced elevations of alanine aminotransferase and aspartate aminotransferase. HSCs were found to undergo apoptosis and decreased expression of p-Smad2 and p- AKT in luteolin-treated animals. Conclusions This study demonstrates that luteolin prevents the progression of liver fibrosis through multiple mechanisms and indicates that luteolin has potential for effective treatment of liver fibrosis. [ABSTRACT FROM AUTHOR]

Background & Aims Common bile duct ligation ( CBDL) rats is an accepted experimental model of hepatopulmonary syndrome ( HPS), defined as liver disease and intrapulmonary vascular dilatation and hypoxaemia. Pulmonary Akt and ERK activation followed by angiogenesis in the later stages of CBDL, contribute to the pathogenesis of HPS. However, the mechanisms behind Akt and ERK activation remain undefined. Pulmonary injury induced by increased bilirubin, endotoxin and inflammatory mediators occurs in the early stages of CBDL. We assessed the effects of relieving pulmonary injury on Akt and ERK activation and on the development of HPS following CBDL. Methods Pulmonary injury, angiogenesis, arterial oxygenation, cell proliferation and, phospho-Akt and ERK1 were evaluated in CBDL animals with or without caspase-3 inhibition (Z-DEVD-FMK). Pulmonary injury was assessed by histology and quantifying apoptosis and aquaporin-1 ( AQP1) levels. Lung angiogenesis was assessed by quantifying AQP1 level, vWF-positive cells and microvessel count. Results Pulmonary apoptosis and caspase-3 activation were markedly increased in the early stages of CBDL. Caspase-3 inhibition alleviated apoptosis, the reduction in AQP1, phospho-Akt and ERK1 levels and pulmonary injury 1 week after CBDL. Caspase-3 inhibition also reduced AQP1, phospho-Akt and ERK1 levels, vWF-positive cells, cell proliferation, microvessel count, and microvascular dilatation and improved arterial oxygenation 3 weeks following CBDL. Conclusions Caspase-3 inhibition alleviates pulmonary injury, thereby preventing angiogenesis as well as the development of HPS in CBDL rats. These effects are related to the regulation of the Akt and ERK1 pathways. [ABSTRACT FROM AUTHOR]

Background & Aims Portal hypertension results from endothelial dysfunction after liver injury caused in part by abnormal production of endothelial cell derived nitric oxide synthase (eNOS). Here, we have postulated that endothelial mechanosensing pathways involving integrin-linked kinase (ILK) may play a critical role in portal hypertension, eNOS expression and function. In this study, we investigated the role of ILK and the small GTP-binding protein, Rho, in sinusoidal endothelial cell (SEC) eNOS regulation and function. Methods Primary liver SECs were isolated using standard techniques. Liver injury was induced by performing bile duct ligation ( BDL). To examine the expression of Rho and ILK in vivo during wound healing, SECs were infected with constitutively active Rho (V14), a dominant negative Rho (N19) and constructs encoding ILK and a short hairpin-inhibiting ILK. Results Integrin-linked kinase expression was increased in SECs after liver injury; endothelin-1, vascular endothelial growth factor, and transforming growth factor beta-1 stimulated ILK expression in SECs. ILK expression in turn led to eNOS upregulation and to enhance eNOS phosphorylation and NO production. ILK knockdown or ILK (kinase) inhibition reduced eNOS mRNA expression, promoter activity, eNOS expression and ultimately NO production. In contrast, ILK overexpression had the opposite effect. Inhibition of ILK activity also disrupted the actin cytoskeleton in isolated SECs. Rho overexpression suppressed phosphorylation of the serine-threonine kinase, Akt and inhibited eNOS phosphorylation. Finally, inhibition of Rho function with the RGS domain of the p115-Rho-specific GEF (p115-RGS) significantly increased eNOS phosphorylation. Conclusions Our data suggest a potential role for ILK, the cytoskeleton and ILK signalling partners including Rho in regulating intrahepatic SEC eNOS expression and function. [ABSTRACT FROM AUTHOR]

Background: Surgical resection continues to be the current standard treatment for distal bile duct carcinoma (DBC), as no effective alternative treatment exists. However, even after resection, the long-term prognosis is poor. Simple biomarkers that can predict response or toxicity, and which are applicable to all community oncology settings worldwide, have not been identified. Differential white-cell counts, such as the neutrophil-to-lymphocyte ratio (NLR), as markers of inflammation, may be simple and readily available biomarkers. This study aimed to determine whether the NLR can be used as a predictor of surgical outcome in patients with DBC. Materials and Methods: We enrolled 91 DBC patients who had undergone pancreatoduodenectomy (PD) at a single institution between April 2000 and December 2013. Blood was sampled on admission for determination of NLR. An NLR of ≥5 was selected as the cut-off value for validation. Results: Seventeen patients had an NLR of ≥5 (Group 1; 18.7%), while 74 had an NLR of <5 (Group 2; 81.3%). The 1-, 3- and 5-year survival rates for Group 1 patients were 75.9, 34.5 and 34.5%, respectively, while those for Group 2 patients were 94.8, 55.2 and 46.6%, respectively (p = 0.02). There were no significant inter-group differences in clinicolaboratory background factors such as the mean operation time, bleeding volume, tumor size, CRP, neutrophil count and lactate dehydrogenase (LDH) level. On the other hand, there were significant inter-group differences for albumin level (p = 0.011), lymphocyte count (p = 0.001) and NLR (p < 0.001). Multivariate analyses were performed for factors such as gender, age, maximum tumor diameter, drainage method, operation time, bleeding volume, pathology, albumin, CRP, neutrophil count, lymphocyte count, LDH and NLR. The results revealed that NLR (odds ratio, 2.032; 95% CI, 0.999-4.134; p = 0.040) was associated with postoperative overall survival. Conclusions: An NLR of ≥5 predicts a poor outcome in patients undergoing PD for DBC. NLR is an independent indicator of overall survival for such patients. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Residual lithiasis found in the main bile duct entails the presence, at the site, of one or more calculi, consequent to a surgical procedure for gallbladder or common bile duct lithiasis. Currently, the surgical community is trying to treat this condition via a minimally invasive procedure: endoscopic retrograde cholangiopancreatography. A bile duct obstacle can be diagnosed based on several imagistic methods, the most important ones being: the ultrasound, computed tomography or the cholangio- MRI. These methods aim to detect an obstacle, to establish its nature, location and size. The decision to apply these imagistic diagnostics techniques or different ones, depending on their indications, contraindications or their succession belongs, entirely, to the radiologist. In this sense, we compared the results we have obtained so far to specialised studies and research, in an attempt to establish the highest reliability level in the diagnostic imaging investigation of the common bile duct lithiasis whose absence would make impossible an endoscopic retrograde colangiopancreatography. [ABSTRACT FROM AUTHOR]

Background Historically, hilar bile duct resection (HBDR) has been regarded as the choice of treatment for Bismuth types I and II hilar cholangiocarcinoma (HCCA). The present study aimed to evaluate the advantages of major liver resection (MLR) in the treatment of patients with Bismuth types I and II HCCA when compared with HBDR. Materials and methods Between January 2005 and September 2012, in total, 52 patients with Bismuth types I and II HCCA who underwent HBDR alone or MLR were included for retrospective analysis. The intraoperative outcomes, postoperative complications, and oncological outcomes including recurrence and overall or disease-free survival rate were compared. Results The MLR group had significantly higher curative resection rates compared with the HBDR group (95% versus 62.5%, P = 0.021) and lower tumor recurrence (28% versus 63%, P = 0.049), albeit with longer operating time (395.5 ± 112.7 versus 270.9 ± 98.8, P < 0.001), and higher blood transfusion requirements (70% versus 16%, P < 0.001). MLR resulted in significantly higher overall postoperative morbidity (70% versus 34.4%, P = 0.012), compared with HBDR alone. When restricted to R0 resections for all the procedures, MLR significantly increased the overall postoperative survival rate compared with the HBDR group (P = 0.016); the overall survival rate at 1, 3 y was 68.4% and 60.8% for MLR group and 59.6% and 21.9% for HBDR group, respectively. Also, the disease-free survival rate was significantly higher in patients who underwent MLR, as compared with those who underwent HBDR (53.2% versus 0% at 3 y, P = 0.005). Conclusions Our study has shown that MLR results in higher curative resections, fewer recurrences, and increased postoperative survival rate for Bismuth types I and II HCCA as compared with HBDR alone. However, there is a need for well-designed, multicenter studies to be undertaken to better inform a decision on the standard treatment for Bismuth types I and II HCCA. [ABSTRACT FROM AUTHOR]

Background/Aims: Choledocholithiasis is a common complication of cholecystolithiasis, occurring in 15-20% of patients who have gallbladder stones. Endoscopic retrograde cholangio-pancreatography is the standard treatment. When this is not possible or not feasible, percutaneous transhepatic stone removal is an alternative treatment. In this retrospective study, we analyze 110 patients who were treated with percutaneous transhepatic removal of Common Bile Duct (CBD) stones. Patients and Methods: Between March 1998 and September 2013 110 patients (61 men, 49 women; aged 14-96, mean age 69.7 years) with confirmed bile duct stones were included. PTC was done using ultrasound and fluoroscopy. Balloon dilatation of the papilla was done with 8-12 mm balloons. If stone size exceeded 10 mm, mechanical lithotripsy was performed. Stones were then removed by percutaneous extraction or evacuation into the duodenum. Results: In 104 patients (104/110; 94.5%) total stone clearance of the CBD was achieved. A total of 12 complications occurred (10.9%), graded with the Clavien-Dindo scale as IVa, IVb, and V, respectively; hypoxia requiring resuscitation, sepsis and death due to ongoing cholangiosepsis (n = 1, 4, 1). Minor complications I, II, and IIIa included: small liver abscess, pleural empyema, transient hemobilia and mild fever (n = 1, 1, 2, 2). Conclusion: Percutaneous removal of CBD stones is an effective alternative treatment, when endoscopic treatment is contra-indicated, fails or is not feasible. It is effective, has a low complication rate and using deep sedation potentially requires only a very limited number of treatment sessions. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We report a unique first case of benign heterotopic pancreas arising within the proximal hepatic bile duct, containing a focus of intraductal papillary mucinous neoplasm (IPMN). The condition was diagnosed on pathological explant after left hepatic lobectomy with total extrahepatic bile duct excision. [ABSTRACT FROM AUTHOR]

Objective--To describe techniques for endoscopic retrograde cholangiography (ERC) and endoscopic retrograde biliary stenting of the common bile duct (CBD) for minimally invasive treatment of extrahepatic bile duct obstruction (EHBDO) in dogs. Design--Experimental study and clinical report. Animals--7 healthy research dogs and 2 canine patients. Procedures--ERC and endoscopic retrograde biliary stenting were performed in healthy purpose-bred research dogs and client-owned dogs with a diagnosis of EHBDO that underwent an attempted biliary stent procedure. Research dogs were euthanized after completion of the procedure and underwent necropsy. With dogs under general anesthesia, the pylorus was cannulated with a side-view duodenoscope, and the duodenum was entered. The major duodenal papilla (MDP) and minor duodenal papilla were then identified, and the MDP was cannulated. Endoscopic retrograde cholangiography and endoscopic retrograde biliary stenting were attempted with the aid of endoscopy and fluoroscopy in all dogs. Procedure time, outcome for duodenal and MDP cannulation, and success of stent placement were recorded. Results--Endoscopic retrograde cholangiography was successfully performed in 5 of 7 research dogs and in 1 of 2 patients. Biliary stenting was achieved in 4 of 7 research dogs and 1 of 2 patients, with a polyurethane (n = 4) or self-expanding metallic stent (1). One patient had a mass such that visualization of the MDP was impossible and no attempt at biliary cannulation could be made. After placement, stent patency was documented by means of contrast cholangiography and visualization of biliary drainage into the duodenum intra-operatively. No major complications occurred during or after the procedure in any patient. Follow-up information 685 days after stent placement in 1 patient provided evidence of biliary patency on serial repeated ultrasonography and no evidence of complications. Conclusions and Clinical Relevance--ERC and endoscopic retrograde biliary stenting were successfully performed in a small group of healthy dogs and 1 patient with EHBDO, but were technically challenging procedures. Further investigation of this minimally invasive technique for the treatment of EHBDO in dogs is necessary before this may be considered a viable alternative to current treatment methods. [ABSTRACT FROM AUTHOR]

The safety and efficacy of endoscopic sphincterotomy with large balloon dilation (EPLBD) are unclear. This study compares the safety and efficacy between EPLBD and endoscopic sphincterotomy (EST). Patients and Methods. Literatures were searched for randomized controlled trials in PUBMED, EMBASE, and Cochrane Library. Outcome measurements included adverse events; stone removal rate; requirement of mechanical lithotripsy. Results. Four RCTs with a total of 596 patients were included. Three RCTs compared EPLBD versus EST alone for stone removal; one RCT compared EPLBD versus EST plus mechanical lithotripsy for stone removal. Pooled data from three RCTs showed that there was no significant difference in the adverse event of ERCP. A significantly higher cholangitis rate was seen in patients who received EST plus mechanical lithotripsy, compared to those treated with EPLBD (13.3% versus 0.0, P=0.026). No statistical difference was found between EPLBD and EST for stone removal rate. Significant differences in requirement of mechanical lithotripsy were seen with removal of large stones (>15 mm), with EPLBD reducing the use of mechanical lithotripsy (RR: 0.73; 95% CI: 0.54–0.99). Conclusions. EPLBD and EST have similar efficacy and safety for bile duct stones clearance. With larger stones, EPLBD can reduce requirement of mechanical lithotripsy. [ABSTRACT FROM AUTHOR]

Background: Hilar cholangiocarcinoma is the most common malignant tumor affecting the extrahepatic bile duct. Surgical treatment offers the only possibility of cure, and it requires removal of all tumoral tissues with adequate resection margins. The aims of this review are to summarize the findings and to discuss the controversies on the extent of surgical resection aiming at cure for hilar cholangiocarcinoma. Methods: The English medical literatures on hilar cholangiocarcinoma were studied to review on the relevance of adequate resection margins, routine caudate lobe resection, extent of liver resection, and combined vascular resection on perioperative and long-term survival outcomes of patients with resectable hilar cholangiocarcinoma. Results: Complete resection of tumor represents the most important prognostic factor of long-term survival for hilar cholangiocarcinoma. The primary aim of surgery is to achieve R0 resection. When R1 resection is shown intraoperatively, further resection is recommended. Combined hepatic resection is now generally accepted as a standard procedure even for Bismuth type I/II tumors. Routine caudate lobe resection is also advocated for cure. The extent of hepatic resection remains controversial. Most surgeons recommend major hepatic resection. However, minor hepatic resection has also been advocated in most patients. The decision to carry out right- or left-sided hepatectomy is made according to the predominant site of the lesion. Portal vein resection should be considered when its involvement by tumor is suspected. Conclusion: The curative treatment of hilar cholangiocarcinoma remains challenging. Advances in hepatobiliary techniques have improved the perioperative and long-term survival outcomes of this tumor. [ABSTRACT FROM AUTHOR]

Background: Holothuria arenicola is the most important and abundant sea cucumber species in the Mediterranean Sea on the Egyptian coast. The present study aims to assess the anti-oxidative and anticholestatic effects of the sea cucumber Holothuria arenicola extract (HaE) in a model of bile duct ligation in male albino rats. Methods: Fifty four male Wistar albino rats were assigned into two main groups, the Sham-operated control and bile duct ligated (BDL) group. After 14 days of surgery, the animals of the group I (Sham control) received distilled water only for 7, 14 and 28 days. Second group (BDL group) was divided into 2 subgroups, animals of these subgroups treated for 7, 14 and 28 consecutive days as follow: subgroup I (BDL), rats of this subgroup administered distilled water orally. Subgroup II (HaE), animals of this subgroup treated orally with HaE (200 mg/kg body weight). Results: The HaE revealed significant antifibrotic effect as evident by decreasing the levels of total conjugated and unconjugated bilirubin and the activities of serum aminotransferases (ASAT and ALAT) and alkaline phosphatase (ALP) as well as malondialdehyde (MDA) level, and increasing the serum albumin, glutathione reduced (GSH) levels. Treatment with HaE normalized the antioxidant enzyme, glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) activities activities. Conclusion: The present prospective study correlated the antifibrotic effect of HaE to its direct antioxidant effect that can be related to its contents of phenolic compounds specially chlorogenic acid, pyrogallol, rutin and coumaric acid. [ABSTRACT FROM AUTHOR]

Among biliary tract cancers, gallbladder cancer (GBC) is a potentially lethal malignancy with abysmal long-term survival. Surgery is central to the management of GBC, and presently, provides the only ray of hope for long-term survival. Radical cholecystectomy, which includes cholecystectomy with a limited hepatic resection, regional lymphadenectomy and adjacent organ resection if required is used to encompass the tumor with negative margins - R'0' resection is the standard surgical treatment for the management of GBC. Absence of randomized controlled trials to address various surgical controversies due to rarity of disease in western world, advanced disease at presentation, high frequency of unresectability/inoperability at surgery, deficient neoadjuvant/adjuvant strategies and nihilistic views of oncologists due to aggressive disease biology has resulted in marked heterogeneity in surgical strategies employed to manage GBC across the surgical centers globally. [ABSTRACT FROM AUTHOR]

Background: Prevalence of hepatic steatosis following pylorus-preserving pancreaticoduodenectomy (PPPD) is high. This study intended to reveal the prevalence and patterns of de novo hepatic steatosis following PPPD. Methods: We investigated postoperative de novo hepatic steatosis following PPPD (n = 101) with a control group of bile duct resection (BDR) (n = 54). Results: At postoperative 1 year, hepatic steatosis occurred in 21 of 82 patients (25.6%) of PPPD group and in 2 of 47 patients (4.3%) of BDR group (p = 0.001). Thereafter, at 2 to 5 years, a high prevalence of hepatic steatosis persisted in the PPPD group, but no further occurrence developed in BDR group. Once steatosis developed, it persisted until the end of the study period or patient death. Five-year cumulative incidence of hepatic steatosis was 26.7% in the PPPD group and 3.7% in BDR group (p < 0.001). Univariate analyses showed that patient sex, age, body mass index, blood lipid profile, recurrence of tumor, and diabetes did not have significant influence on the development of hepatic steatosis following PPPD. Conclusions: De novo hepatic steatosis may develop in a not negligible proportion of patients undergone PPPD. Multicenter studies with a high number of patients are needed to elucidate its pathogenesis and to find effective treatment for pancreaticoduodenectomy-associated hepatic steatosis. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Postcholecystectomy syndrome has been a long-standing source of frustration for surgeons. The objective of this study was to assess the feasibility and safety of laparoscopic remnant cholecystectomy (LRC) and laparoscopic transcystic common bile duct (CBD) exploration (LTCBDE) when adopted as the management for gallbladder/cystic duct remnant with stones and choledocholithiasis (GRSC) after cholecystectomy. Patients and Methods: This is a retrospective study of 11 patients who underwent surgeries for GRSC: the first 4 patients (Group 1) underwent open remnant cholecystectomy and CBD exploration, whereas the last 7 patients (Group 2) underwent LRC with LTCBDE successfully. Demographic data and perioperative parameters were analyzed and compared between the two groups. Results: All 11 patients had undergone cholecystectomy for symptomatic gallstone diseases. These patients had a mean age of 62 years. The time interval between cholecystectomy and the diagnosis of GRSC ranged from 4 years to 23 years (mean, 13 years). There was a significant reduction in postoperative hospital stay (5.00±1.41 versus 2.14±1.77 days, P=.034) and blood loss (35.00±10.00 versus 14.29±7.87 mL, P=.011) in Group 2 compared with Group 1. The 30-day morbidity rate was 9.1%. At a mean follow-up of 24 months (range, 6-45 months), no symptoms had recurred, and no mortality was recorded in this study. Conclusions: LRC and LTCBDE for GRSC are safe and feasible and could be offered as a choice in centers performing advanced laparoscopic procedures. [ABSTRACT FROM AUTHOR]

The major drawback of the current common bile duct ligation (CBDL)-induced hepatopulmonary syndrome (HPS) animal model is the extremely high mortality rate that hinders experimental studies. The purpose of this study was to investigate an improved method of CBDL with the goal of developing a simple and reproducible rat HPS model after a single CBDL treatment. Two groups of male Sprague–Dawley rats underwent separate methods of CBDL: (1) the upper common bile duct ligation (UCBDL) group (n = 40), in which the first ligature was made near the junction of the hepatic ducts, and the second ligature was made above the entrance of the pancreatic duct; (2) the middle of the common bile duct ligation (MCBDL) group (n = 40), in which the first ligature was made in the middle of the common bile duct, and the second ligature was made above the entrance of the pancreatic duct. The CBDL-induced HPS rats were evaluated by pulse oximeter, arterial blood analysis, histopathology, and cerebral uptake of intravenous technetium-99m-labeled albumin macroaggregates (which reflects intrapulmonary vascular dilation). The mortality rates of the UCBDL group and the MCBDL group were 42.5% and 77.5%, respectively (P < 0.05). These results suggest that the UCBDL, a single improved procedure, provides a better method compared to the established HPS model, because of the relatively high success rate and the decreased risk of complications. [ABSTRACT FROM AUTHOR]

Project Cholestasis liver fibrosis has been increasingly recognized as a cause of high morbidity and mortality in humans. The accumulation of toxic bile salts in a bile duct ligation (BDL) animal model plays a pivotal role in the induction of liver fibrosis. Cholestatic liver fibrosis is characterized by excessive collagen production and deposition, which is mediated by reactive oxygen species (ROS). Molybdenum is an essential micronutrient trace element which acts as a cofactor in many detoxification system enzymes. The aim of the present study was to evaluate the antifibrotic effect of sodium molybdate on liver cholestasis induced by bile duct ligation in rats. Procedure After BDL, rats were given sodium molybdate (0.05 or 0.1 or 0.2 g/kg) or urosodeoxycholic acid (UDCA, 25 mg/kg) via intragastric gavage for 45 consecutive days (once per day). Results BDL drastically increased the serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin and direct bilirubin, whereas it reduced the levels of antioxidant enzymes, superoxide dismutase and catalase in the liver. Treatment of BDL rats with sodium molybdate significantly attenuated these changes. As determined by Masson's trichrome staining, BDL markedly induced the liver fibrosis. These alterations were also significantly attenuated by sodium molybdate administration. Conclusions The results of this study indicate the hepatoprotective and antifibrotic effect of sodium molybdate in the cholestatic liver. Sodium molybdate, by inhibiting the activation of Ito cells, decreases the collagen production in the liver. The antifibrotic effect of sodium molybdate is likely due to the antioxidative and free radical scavenging effects of this trace element. [ABSTRACT FROM AUTHOR]

A 32-year-old man was admitted to our hospital due to a traffic accident. Intraoperative observations revealed hemoperitoneum, splenic transection, pancreatic tail contusion, comminuted injury in the porta hepatis, rupture in the left hepatic duct, an irregular crevasse in the ductus hepaticus communis, the caudate lobe was transversely broken on the left, and under the gap, there was a fracture in retrohepatic inferior vena cava with huge retroperitoneal hematoma. We carried out a ligation of the left hepatic duct and the proper hepatic artery. Postoperation, the man recovered smoothly. At 5 years and 5 months postoperation, MRI showed that the left liver had atrophied partly. So, we consider that the ligation of the left hepatic duct is a safe procedure for patients without cirrhosis under the conditions of ligation of the proper hepatic artery. [ABSTRACT FROM AUTHOR]

Objectives Adequate hepatic arterial ( HA) flow to the bile duct is essential in liver transplantation. This study was conducted to determine if the ratio of directly measured HA flow to weight is related to the occurrence of biliary complications after deceased donor liver transplantation. Methods A retrospective review of 2684 liver transplants carried out over a 25-year period was performed using data sourced from a prospectively maintained database. Rates of biliary complications (biliary leaks, anastomotic and non-anastomotic strictures) were compared between two groups of patients with HA flow by body weight of, respectively, <5 ml/min/kg ( n = 884) and ≥5 ml/min/kg ( n = 1800). Results Patients with a lower ratio of HA flow to weight had higher body weight (92 kg versus 76 kg; P < 0.001) and lower HA flow (350 ml/min versus 550 ml/min; P < 0.001). A lower ratio of HA flow to weight was associated with higher rates of biliary complications at 2 months, 6 months and 12 months (19.8%, 28.2% and 31.9% versus 14.8%, 22.4% and 25.8%, respectively; P < 0.001). Conclusions A ratio of HA flow to weight of < 5 ml/min/kg is associated with higher rates of biliary complications. This ratio may be a useful parameter for application in the prevention and early detection of biliary complications. [ABSTRACT FROM AUTHOR]

Biliary tract cancers (including gallbladder cancer, cholangiocarcinoma, and ampullary tumors) are low-incidence and poor-prognosis malignancies. Surgery, which is the only potentially curative treatment, is usually not feasible due to presentation in late stages of disease. Moreover, for those patients who are resected many die due to disease relapse (both due to locoregional and distant spread). Although the 5-year survival rate has improved during the last 15 years for ampullary malignancies, it remains stable for cholangiocarcinoma and gallbladder cancers. Adjuvant treatment aims to improve patient survival following resection. Since the publication of the ESPAC-3 clinical trial (ampullary subgroup), adjuvant chemotherapy is considered standard of care by many countries resection of ampullary malignancies. In contrast, available data are not so clear with respect to the benefit from chemotherapy or radiotherapy for gallbladder cancer and cholangiocarcinoma, and results from prospective studies are awaited to clarify this. The rationale for adjuvant treatment in biliary tract malignancies and the most important available studies are discussed in this review. [ABSTRACT FROM AUTHOR]

Background and aim: To audit short- and long-term outcomes after laparoscopic common bile duct exploration (LCBDE) and factors influencing the success of the laparoscopic treatment. Methods: From January 1999 to December 2011, 288 patients (93 males) underwent a single-stage laparoscopic cholecystectomy combined with LCBDE in two Finnish Hospitals. Short-term outcome data were collected prospectively. Long-term outcomes were examined retrospectively. The main measures of outcome were the success of laparoscopic CBD stone clearance and recurrence of CBD stones in the long-term, with 30-day mortality, morbidity, and the length of postoperative hospital stay as secondary outcome measures. Results: CBD stones were successfully removed by one-stage laparoscopic procedure in 232 of the 279 patients (83.2 %) with verified CBD stones and after conversion to open surgery in additional 28 patients (93.2 %). Nineteen patients (6.8 %) having residual stones after surgery were successfully treated with postoperative ERCP. On multivariate analysis, the independent factors associated with a failed laparoscopic stone clearance were stone size over 7 mm [OR 3.51 (95 % CI 1.53-8.03), p = 0.003], difficult anatomy [OR 18.01 (5.03-64.49), p < 0.001] and transcholedochal approach [OR 2.98 (1.37-4.47), p = 0.006]. Laparoscopic stone clearance also failed in all 11 patients having impacted stones at the ampulla of Vater. Cumulative long-term recurrence rate was 3.6 % at 5 years and 6.0 % at 10 years. Thirty-day mortality was 0.3 % and morbidity 12.2 %. Postoperative hospital stay was median 2 (IQR 1-3) days after transcystic CBD removal and 4 (IQR 3-7) days after transcholedochal CBD removal, p < 0.001. Conclusion: Our results show that one-stage LC combined with LCBDE stone clearance is safe and effective in most patients thus reducing the number of additional, potentially dangerous endoscopic procedures. Moreover, large or impacted stones are a risk factor for failed stone clearance. [ABSTRACT FROM AUTHOR]

Background The independent influence of advanced age on outcomes in contemporary series treated by early cholecystectomy is undetermined. Methods Elderly patients, aged 80 years and older, with histology proven acute cholecystitis treated by cholecystectomy on initial presentation between 2005 and 2011 were compared to all others. Results In total, 411 patients had histologically proven acute cholecystitis, of whom 71 (17%) were aged 80 years and older. Elderly patients were more likely to have ischaemic heart disease, underlying diabetes and chronic renal failure. There was greater conversion from laparoscopic to open surgery in the elderly (21% versus 7%; P = 0.001). Elderly patients were more likely to have gangrenous cholecystitis (44% versus 31%; P = 0.033) and common bile duct stones (27% versus 17%; P = 0.048). Elderly patients had more complications (31% versus 13%; P < 0.001), a higher mortality rate (4% versus 1%; P = 0.038) and a longer median post-operative length of stay (7 days versus 3 days; P < 0.001). Age ≥ 80 ( P = 0.004) was an independent risk factors for complications. Conclusion Age 80 years and older is independently associated with increased morbidity following cholecystectomy for treatment acute cholecystitis at initial presentation. [ABSTRACT FROM AUTHOR]

Objectives To establish the model of common bile duct repair in pig and compare the acellular dermal with biliary intestinal anastomosis. Methods Common bile ducts were removed partly or completely, and then their common bile ducts were repaired by acellular dermal matrix (ADM), the repair effects were compared between the acellular dermal matrix and Biliary intestinal anastomosis. Results In 33 normal experiment pigs, 30 pigs survived over 2 weeks postoperation. The success rate of operation was 91%. The operation time of ADM group was obviously shorter than Biliary intestinal anastomosis group (P < 0.05). Median survival time of ADM group was obviously longer than Biliary intestinal anastomosis group (P < 0.05). Conclusion Shorter operation time, fewer complications and longer survival time all imply that the effect of ADM for repairing common bile duct is good. [ABSTRACT FROM AUTHOR]

Hepatic fibrosis is a disease caused by a wide variety of chronic diseases that affect the liver after different insults, and the only treatment is liver transplantation. The pathogenesis of liver fibrosis involves complex interaction between cells and the extracellular matrix of the liver tissue, which is mediated by cytokines that modulate the progression of fibrosis. The aim of this study was to quantitatively analyze the profile of pro-inflammatory (IL-6 and TNF-∝) and anti-inflammatory (IL-10) cytokines in the liver of rats with different degrees of fibrosis induced by bile duct ligation (BDL). Twenty rats were subjected to BDL procedure and euthanized after 2, 4, and 6 weeks of fibrosis induction for removal of liver and quantification of cytokines by sandwich ELISA method. After 4 weeks, an increase of all cytokines was observed, and after 6 weeks, all these cytokines were reduced. Among the pro-inflammatory cytokines, the TNF-∝ showed a statistically significant increase and decrease, respectively on the fourth and sixth week, when compared to IL-6, which was not statistically significant in any week after BDL. The IL-10 was significantly elevated on the fourth week, followed by a moderate decrease on week six. These results indicate that TNF-∝ is the main cytokine in biliary fibrosis progression mainly in the intermediate stage. In addition, the IL-10 acts at this stage by limiting the production of the pro-inflammatory cytokine TNF-∝ in an attempt of an endogenous control of the disease progression. [ABSTRACT FROM AUTHOR]

Background and Purpose Activation of hepatic stellate cells ( HSCs) is a crucial step in the pathogenesis of hepatic fibrosis. Histone deacetylase ( HDAC) is an attractive target in liver fibrosis because it plays a key role in gene expression and cell differentiation. We have developed a HDAC inhibitor, N-hydroxy-7-(2-naphthylthio)heptanomide ( HNHA), and investigated the anti-fibrotic activity of HNHA in vitro and in vivo. Experimental Approach We investigated the anti-fibrotic effect of HNHA on mouse and human HSC activation in vitro and in the liver of bile duct-ligated ( BDL) rats in vivo using cell proliferation assays, cell cycle analysis, biochemical assay, immunohistochemistry and Western blots. Liver pathology was assessed with histochemical techniques. Key Results HNHA inhibited proliferation and arrested the cell cycle via p21 induction in HSCs. In addition, HNHA induced apoptosis of HSCs, which was correlated with reduced COX-2 expression, NF-κ B activation and cell death signals. HNHA restored liver function and decreased the accumulation of extracellular matrix in the liver via suppression of HSC activation in BDL rats in vivo. HNHA administration also increased survival in BDL rats. Conclusions and Implications HNHA improved liver function, suppressed liver fibrosis and increased survival of BDL rats, accompanied by reduction of cell growth, activation and survival of HSCs. These findings show that HNHA may be a potent anti-fibrosis agent against hepatic fibrosis because of its multi-targeted inhibition of HSC activity in vivo and in vitro. [ABSTRACT FROM AUTHOR]

The article presents a case studies regarding the use of rescue ballon dilation of the ampulla to retrieve the impacted memory basket with entrapped stones in patients with choledocholithiasis. The fractured basket in a 73-year-old woman was successfully removed from the distal common bile duct (CBD) following a ballon dilation. The 55-year-old woman was discharged with good condition after undertaking laparoscopic cholecystectomy and endoscopic retrograde cholangiopancreatography (ERCP).

Background: Recent studies have indicated that preoperative biliary drainage (PBD) should not be routinely performed in patients suffering from obstructive jaundice before surgery. The severity of jaundice that mandates PBD has yet to be defined. Our aim was to investigate whether PBD is truly justified in severely jaundiced patients before pancreaticoduodenectomy. The parameters evaluated were overall morbidity, length of hospital stay, and total in-hospital mortality. Methods: From January 2000 to December 2012, a total of 240 patients underwent pancreaticoduodenectomy for periampullary tumors. Group A comprised 76 patients with preoperative serum bilirubin ≥15 mg/dl who did not undergo PBD before surgery. Group B comprised another 76 patients, matched for age and tumor localization (papillary vs. pancreatic head) who underwent PBD 2-4 weeks before pancreaticoduodenectomy and were identified from the same database. Results: Less operative time was required in the 'no PBD' group compared with the 'PBD' group (210 vs. 240 min). Total intraoperative blood loss and blood transfusions were also significantly less in the 'no PBD' group. There was no difference detected in the rate of pancreatic fistula or biliary fistula formation. Group A patients demonstrated significantly lower morbidity than group B (24 vs. 36 %, respectively) and therefore required briefer hospitalization (11 vs. 16 days). Mild infectious complications appear to be the main factor that enhanced morbidity in the PBD group. However, total in-hospital mortality was not significantly different between the two groups. Conclusions: Even severe jaundice should not be considered as an indication for PBD before pancreaticoduodenectomy, as PBD increases infections and postoperative morbidity, therefore delaying definite treatment. [ABSTRACT FROM AUTHOR]

The role of nerve growth factor (NGF) in liver injury induced by bile duct ligation (BDL) remains elusive. This study aimed to investigate the relationship between inflammation and hepatic NGF expression, to explore the possible upstream molecules up-regulating NGF, and to determine whether NGF could protect hepatocytes from oxidative liver injury. Biochemical and molecular detection showed that NGF was up-regulated in cholestatic livers and plasma, and well correlated with systemic and hepatic inflammation. Conversely, systemic immunosuppression reduced serum NGF levels and resulted in higher mortality in BDL-treated mice. Immunohistochemistry showed that the up-regulated NGF was mainly localized in parenchymal hepatocytes. In vitro mechanistic study further demonstrated that TGF-β1 up-regulated NGF expression in clone-9 and primary rat hepatocytes. Exogenous NGF supplementation and endogenous NGF overexpression effectively protected hepatocytes against TGF-β1- and oxidative stress-induced cell death in vitro, along with reduced formation of oxidative adducted proteins modified by 4-HNE and 8-OHdG. TUNEL staining confirmed the involvement of anti-apoptosis in the NGF-exhibited hepatoprotection. Moreover, NGF potently induced Akt phosphorylation and increased Bcl-2 to Bax ratios, whereas these molecular alterations by NGF were only seen in the H2O2-, but not TGF-β1-treated hepatocytes. In conclusion, NGF exhibits anti-oxidative and hepatoprotective effects and is suggested to be therapeutically applicable in treating cholestatic liver diseases. [ABSTRACT FROM AUTHOR]