The Efficacy of Endoscopic Papillary Balloon Dilation for Patients with Acute Biliary Pancreatitis

Background. No study investigated the efficacy and safety of endoscopic papillary balloon dilation (EPBD) for the treatment of acute biliary pancreatitis (ABP). Method. We retrospectively reviewed the effects of EPBD on patients with ABP from February 2003 to December 2012. The general data, findings of image studies, details of the procedure, and outcomes after EPBD were analyzed. Result. Total 183 patients (male/female: 110/73) were enrolled. The mean age was 65.9 years. Among them, 155 patients had mild pancreatitis. The meantime from admission to EPBD was 3.3 days. Cholangiogram revealed filling defects inside the common bile duct (CBD) in 149 patients. The mean dilating balloon size was 10.5 mm and mean duration of the dilating procedure was 4.3 minutes. Overall, 124 patients had gross stones retrieved from CBD. Four (2.2%) adverse events and 2 (1.1%) intraprocedure bleeding incidents but no procedure-related mortality were noted. Bilirubin and amylase levels significantly decreased after EPBD. On average, patients resumed oral intake within 1.4 days. The clinical parameters and outcomes were similar in patients with different severity of pancreatitis. Conclusion. EPBD can be effective and safe for the treatment of ABP, even in patients presenting with severe disease

Combined cholecystectomy in gastric cancer surgery

Background: Many studies have described the risk factors of gallstone formation in gastric cancer patients after gastrectomy, but few studies focus on the management of asymptomatic gallstones. Our goal is to examine the rationale of simultaneous cholecystectomy during gastric cancer surgery, and influence of surgical mortality, morbidity and overall survival after combined cholecystectomy and gastrectomy. Methods: We retrospectively reviewed 445 gastric cancer patients and the gallbladders evaluated by abdominal ultrasound or computed tomography preoperatively and postoperatively. Clinicopathologic factors, including surgical morbidity, mortality and overall survival of combined surgery, were compared between patients receiving gastrectomy with simultaneous cholecystectomy and patients receiving gastrectomy only. We also evaluated the risk factors of gallstone formation after gastrectomy and the probability of subsequent cholecystectomy after gastrectomy in gastric cancer patients with or without asymptomatic gallstones. Results: Of 445 gastric cancer patients, 52 (11.7%) patients had asymptomatic gallstones upon diagnosis of gastric cancer. Among patients with healthy gallbladders, 15.2% developed gallstones after gastrectomy. Men and older patients (age over 60) had significantly higher risk of gallstone formation. Rate of subsequent cholecystectomy in patients with and without preoperative asymptomatic gallstones was 30.8% and 4.5%, respectively (p = 0.005). The rates of mortality and morbidity were not significantly different between combined surgery (3.4%, 24.2%) and gastrectomy only (3.1%, 22%). There was also no significant difference in 5-year survival between combined surgery (61%) and gastrectomy only (63%) groups. Conclusion: Combined cholecystectomy for asymptomatic gallstone in gastric cancer surgery may be considered. It was not associated with increased surgical morbidity or mortality, and had no significant effect on overall survival. (C) 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved

IL-6 regulates Mcl-1L expression through the JAK/PI3K/Akt/CREB signaling pathway in hepatocytes: implication of an anti-apoptotic role during liver regeneration.

AIMS: To investigate the role and the regulation of the long variant of myeloid cell leukemia-1 protein (Mcl-1L) during liver regeneration. BACKGROUND: Liver regeneration is an important phenomenon after liver injury. The rat partial hepatectomy (PH) model was used to characterize liver regeneration and Mcl-1L expression after PH. METHODS: Male Wistar rats were subjected to 70% PH. The expression of mcl-1L mRNA was determined by quantitative RT-PCR, and protein levels were analyzed by Western blot analysis and immunohistochemistry during liver regeneration. Functional evaluations of Mcl-1L were tested using chemical inhibition (flavopiridol), genetic inhibition (siRNA) of Mcl-1L production, and by assaying for annexin V levels and DNA ladder formation. Serum IL-6 levels were determined by enzyme immunoassays; signal transduction of IL-6-regulated Mcl-1L expression was verified by chemical inhibitors and decoy double-stranded oligodeoxynucleotides. RESULTS: High levels of Mcl-1L were observed in remnant tissue at 4 h after PH. Administration of flavopiridol decreased Mcl-1L accumulation and also inhibited liver regeneration. IL-6 administration promoted the accumulation of Mcl-1L in rat hepatocytes, an effect that was impaired by siRNA treatments that reduced Mcl-1L production. Chemical inhibition and decoy oligonucleotide competition demonstrated that IL-6-induced Mcl-1L production required signaling mediated by JAK kinase, phosphoinositide 3-kinase (PI3K), and cAMP response-element-binding (CREB) proteins. CONCLUSION: Mcl-1L is an anti-apoptotic protein induced during liver regeneration after PH in rats. The expression of Mcl-1L is induced by IL-6 through the JAK/PI3K/Akt/CREB signaling pathway. Chemotherapy drugs that depend on Mcl-1L- or IL-6-related signaling should be considered carefully before use in patients undergoing hepatectomy for malignant tumor resection

mRNA and protein expression of Mcl-1L during liver regeneration.

<p>Remnant liver tissue from the indicated time points was used to determine (A) mcl-1 mRNA expression by q-RT-PCR; *P<0.05 and (B) protein levels of Mcl-1L as detected by Western blotting. (C) Parafilm sections of the remnant liver were used for Mcl-1 detection by IHC. Magnification, 400×.</p

IL-6 induced angiotensinogen expression in primary cultures of mouse hepatocytes.

<p>(A) Time course of IL-6-induced (10 ng/ml) angiotensinogen protein expression as detected by enzyme immunoassay (n = 3/group). (B) Dose response of IL-6-induced angiotensinogen protein expression after 24 hours of culture, as detected by enzyme immunoassay. Comparisons are between the indicated groups. *<i>P</i><0.05, n = 3.</p

Effect of IL-6-related signaling inhibition on angiotensinogen protein expression and liver regeneration in remnant livers after 70% partial hepatectomy in mice.

<p>Mice were pretreated with chemical inhibitors of JAK2 (AG490, 10 mg/kg subcutaneously), p38 (intraperitoneal SB203580, 15 mg/kg), and STAT3 (intraperitoneal 5,15-DPP, 15 mg/kg) for 4 hours prior to partial hepatectomy. (A) Serum angiotensinogen levels of mice pretreated with different chemical inhibitors (AG490, SB203580, and 5,15-DPP) as detected by enzyme immunoassay. (B) Changes in the ratio of remnant to original liver weight after 70% partial hepatectomy. Remnant liver weight was estimated retrospectively from the excised liver weight after 70% PH. Data are presented as mean ± S.D., and comparisons were made between groups as indicated. *<i>P</i><0.05. (C) Ki-67 staining of regenerated liver tissue sections of the indicated group. Magnification, 400x. (D) Quantification of Ki-67 staining. Data presented here are the quantification of Ki-67-positive nuclei per high-power field. Data are presented as mean percentage of positive nuclei ± S.D., and comparisons were made between groups as indicated. *<i>P</i><0.05.</p

Changes in the ratio of remnant liver weight to original liver weight (RLW/OLW) after 70% partial hepatectomy (PH).

<p>(A) OLW was estimated retrospectively from the excised liver weight after 70% PH. Data are presented as mean ± S.D., and comparisons were made between groups as indicated. *P<0.05. (B) ki67 staining of remnant liver tissue. Magnification, 400×.</p

Schematic of the proposed signal transduction pathway of Mcl-1L induction in hepatocytes during liver regeneration.

<p>IL-6 regulates Mcl-1L expression through the IL-6 dependent JAK/PI3K/Akt/CREB activation pathway in rat hepatocytes.</p

Signal transduction pathways involved in IL-6-induced angiotensinogen expression in primary cultures of mouse hepatocytes.

<p>(A) Inhibition effects of chemical inhibitors 1 to 6 on IL-6-activated signaling mediators detected by Western blotting and quantified by calculating the ratios of phosphorylated/non-phosphorylated protein forms. The ratio in lane 1 is defined as 1. Comparison is between lanes 2 and 3 in each group. *<i>P</i><0.05, n = 3. (B) The effects of different chemical inhibitors on IL-6-induced angiotensinogen protein expression as detected by enzyme immunoassay. Comparison is between the indicated groups. *<i>P</i><0.05, n = 3.</p

JAK/PI3K/Akt/CREB signaling is involved in IL-6-induced Mcl-1L expression in hepatocytes.

<p>(A) Rat hepatocytes were pretreated with chemical inhibitors, JAK Inhibitor InSolution™ 420097 (20 nM), for 1 h prior to IL-6 (10 ng/ml) treatment. After 4 h, the Mcl-1L protein levels were determined by Western blotting. Between-group comparisons are as indicated with *p<0.05. (B) Rat hepatocytes were pretreated with chemical inhibitors, LY294002 (50 µg/mL), PD98059 (50 µg/mL), and staurosporine (20 nM) for 1 h prior to IL-6 (10 ng/ml) treatment. After 4 h, Mcl-1L expression was analyzed by Western blotting. Between-group comparisons are as indicated. *p<0.05. (C) Rat hepatocytes were pretreated with the NF-κB and CREB decoy ODN (10 µM) for 24 h prior to IL-6 treatment. After 4 h, mcl-1 mRNA expression was analyzed by q-RT-PCR. Data are fold-induction relative to the control (Lane 1). Between-group comparisons are as indicated. *p<0.05. (D) Rat hepatocytes were pretreated with JAK Inhibitor InSolution™ 420097 (20 nM), or LY294002 (50 µg/mL) for 1 h prior to IL-6 treatment. After 30 minutes, p-Akt, Akt, p-CREB and CREB were determined by Western blotting. Between-group comparisons are as indicated. *p<0.05.</p