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Hepatic Focal Adhesion Kinase Signaling Modulates Development of Liver Fibrosis
Vol. 223, No. 4S2, October 2016
Scientific Forum: 2016 Clinical Congress
e25
Percent necrosis of tumor post-treatment were comparable between the RFA and TACE group (80% to 90%, p<0.001). Multivariate analysis showed no effect of percent necrosis on recurrence rates (p¼0.57). Subset analysis revealed no statistical difference in recurrence between RFA and TACE groups (1.0% vs 1.2%, P¼0.67)
Kamran Idrees, MD, FACS, Ryan C Fields, MD, Sharon M Weber, MD, FACS, Robert G Martin II, MD, FACS, Carl R Schmidt, MD, FACS, George A Poultsides, MD, FACS New York University School of Medicine, New York, NY, Emory University, Atlanta, GA, Stanford University, Palo Alto, CA
CONCLUSIONS: We demonstrated that recurrence rates are lower for patients who are treated prior to their transplantation (RFA or TACE). Furthermore, we found no difference in percent necrosis or recurrence rates among RFA and TACE group. There was no effect of percent necrosis on recurrence.
INTRODUCTION: Extrahepatic cholangiocarcinoma (EHC) is a rare disease with poor prognosis. Given the lack of data on readmission after resection of EHC, we sought to define the incidence and risk factors associated with readmission among patients who underwent curative intent resection.
Hepatic Focal Adhesion Kinase Signaling Modulates Development of Liver Fibrosis Tammy T Chang, MD, PhD, FACS, Vivian X Zhou University of California, San Francisco, CA
METHODS: Patients who underwent curative-intent resection for hilar or distal cholangiocarcinoma in one of 10 major hepaticpancreatic-biliary centers between 2000 and 2015 were analyzed. Univariable and multivariable regression analyses were performed to identify factors predicting readmission.
INTRODUCTION: Liver cirrhosis is the final common pathway for liver diseases and results in increased liver matrix stiffness. We recently demonstrated that fibrotic levels of matrix stiffness activated mechanotransduction through focal adhesion kinase (FAK) in hepatocytes and led to inhibition of hepatic functions. We hypothesize that FAK activation in hepatocytes also serves to amplify the fibrogenic process and that inhibition of FAK signaling will reduce severity of fibrosis in the setting of pro-fibrotic liver injury. METHODS: We generated mice with hepatocyte-specific deletion of FAK by crossing mice with the FAK gene flanked by loxP sites with mice carrying the Cre recombinase under the albumin promoter (FAK fl/fl; Alb-Cre+). Bile duct ligation was performed on FAK fl/fl; Alb-Cre+ mice and wild-type littermates (FAK fl/fl; Alb-Cre-) to induce cholestatic liver fibrosis. Severity of liver fibrosis was analyzed by histology and by expression of fibrogenic cytokines, stellate cell activation markers, and collagen. RESULTS: FAK fl/fl; Alb-Cre+ mice demonstrated normal liver development. Hepatocytes from FAK fl/fl; Alb-Cre+ mice showed significantly reduced expression of FAK compared to wild-type littermates. Induction of liver fibrosis by bile duct ligation resulted in decreased peri-portal inflammation and severity of fibrosis in FAK fl/fl; AlbCre+ mice compare to wild-type littermates. In addition, livers from FAK fl/fl; Alb-Cre+ showed decreased expression of fibrogenic cytokines, stellate cell activation markers, and collagen compared to wild-types. CONCLUSIONS: FAK signaling in hepatocytes plays a significant role in amplifying the development of liver fibrosis. Blockade of FAK signaling may be an effective anti-fibrotic therapy for liver cirrhosis.
Incidence and Predictors of Readmission after Curative-Intent Resection for Extrahepatic Cholangiocarcinoma: A MultiInstitutional 15-Year Experience from the US Extrahepatic Biliary Malignancy Collaborative Ioannis Hatzaras, MD, MPH, FACS, Shishir Maithel, MD, FACS, Perry Shen, MD, Timothy M Pawlik, MD, MPH, PhD, FACS,
RESULTS: A total of 643 patients were included, of which 541 (84.1%) were resected with curative-intent (284 distal, 257 hilar). Perioperative mortality (4.5%) was excluded from the analysis. Median age was 67.1 and 61.6% of patients were male. Surgery consisted of bile duct resection only in 96 (17.8%), bile duct and liver resection in 215 (40%), and pancreatoduodenectomy in 227 (42.2%). Thirty-day morbidity was 64.6% (34.0% major). Median length of hospital stay (LOS) was 10 days (IQR: 7 - 15). Thirty-day readmission rate was 21.1%; in multivariate analysis, 30-day readmission was independently associated with the incidence of postoperative complications [OR¼5.7, 95% CI, (2.3 e 14.5)], specifically deep/organ space infection [OR 3.7 (1.7 e 7.9)], shorter LOS [LOS8 days, OR: 4.5, 95% CI: (2.2 e 9.1)]. CONCLUSIONS: Readmission after surgery for EHC was common as 1 in 5 patients experienced a readmission. Patients with postoperative complications, specifically deep/organ space infection, and patients discharged early were at higher risk. Strategies focusing on early postoperative clinic visit may reduce the risk of readmission.
Influence of Surgical Volume on Cost Variations for Pancreatic Surgery Howard W Nelson-Williams, MD, MPH, Faiz Gani, MBBS, Timothy M Pawlik, MD, MPH, PhD, FACS Johns Hopkins University School of Medicine, Baltimore, MD INTRODUCTION: In this era of quality improvement and cost efficiency, the economic impact of volume-driven care is understudied. The objective of this study was to assess the influence of hospital volume on inpatient cost variations after pancreatic surgery. METHODS: The Nationwide Inpatient Sample was used to identify patients undergoing elective pancreatic surgery from 2001 to 2012. Charges for inpatient care were derived from the administrative dataset and hospital cost-to-charge ratios were used to compute
Scientific Forum: 2016 Clinical Congress
e25
Percent necrosis of tumor post-treatment were comparable between the RFA and TACE group (80% to 90%, p<0.001). Multivariate analysis showed no effect of percent necrosis on recurrence rates (p¼0.57). Subset analysis revealed no statistical difference in recurrence between RFA and TACE groups (1.0% vs 1.2%, P¼0.67)
Kamran Idrees, MD, FACS, Ryan C Fields, MD, Sharon M Weber, MD, FACS, Robert G Martin II, MD, FACS, Carl R Schmidt, MD, FACS, George A Poultsides, MD, FACS New York University School of Medicine, New York, NY, Emory University, Atlanta, GA, Stanford University, Palo Alto, CA
CONCLUSIONS: We demonstrated that recurrence rates are lower for patients who are treated prior to their transplantation (RFA or TACE). Furthermore, we found no difference in percent necrosis or recurrence rates among RFA and TACE group. There was no effect of percent necrosis on recurrence.
INTRODUCTION: Extrahepatic cholangiocarcinoma (EHC) is a rare disease with poor prognosis. Given the lack of data on readmission after resection of EHC, we sought to define the incidence and risk factors associated with readmission among patients who underwent curative intent resection.
Hepatic Focal Adhesion Kinase Signaling Modulates Development of Liver Fibrosis Tammy T Chang, MD, PhD, FACS, Vivian X Zhou University of California, San Francisco, CA
METHODS: Patients who underwent curative-intent resection for hilar or distal cholangiocarcinoma in one of 10 major hepaticpancreatic-biliary centers between 2000 and 2015 were analyzed. Univariable and multivariable regression analyses were performed to identify factors predicting readmission.
INTRODUCTION: Liver cirrhosis is the final common pathway for liver diseases and results in increased liver matrix stiffness. We recently demonstrated that fibrotic levels of matrix stiffness activated mechanotransduction through focal adhesion kinase (FAK) in hepatocytes and led to inhibition of hepatic functions. We hypothesize that FAK activation in hepatocytes also serves to amplify the fibrogenic process and that inhibition of FAK signaling will reduce severity of fibrosis in the setting of pro-fibrotic liver injury. METHODS: We generated mice with hepatocyte-specific deletion of FAK by crossing mice with the FAK gene flanked by loxP sites with mice carrying the Cre recombinase under the albumin promoter (FAK fl/fl; Alb-Cre+). Bile duct ligation was performed on FAK fl/fl; Alb-Cre+ mice and wild-type littermates (FAK fl/fl; Alb-Cre-) to induce cholestatic liver fibrosis. Severity of liver fibrosis was analyzed by histology and by expression of fibrogenic cytokines, stellate cell activation markers, and collagen. RESULTS: FAK fl/fl; Alb-Cre+ mice demonstrated normal liver development. Hepatocytes from FAK fl/fl; Alb-Cre+ mice showed significantly reduced expression of FAK compared to wild-type littermates. Induction of liver fibrosis by bile duct ligation resulted in decreased peri-portal inflammation and severity of fibrosis in FAK fl/fl; AlbCre+ mice compare to wild-type littermates. In addition, livers from FAK fl/fl; Alb-Cre+ showed decreased expression of fibrogenic cytokines, stellate cell activation markers, and collagen compared to wild-types. CONCLUSIONS: FAK signaling in hepatocytes plays a significant role in amplifying the development of liver fibrosis. Blockade of FAK signaling may be an effective anti-fibrotic therapy for liver cirrhosis.
Incidence and Predictors of Readmission after Curative-Intent Resection for Extrahepatic Cholangiocarcinoma: A MultiInstitutional 15-Year Experience from the US Extrahepatic Biliary Malignancy Collaborative Ioannis Hatzaras, MD, MPH, FACS, Shishir Maithel, MD, FACS, Perry Shen, MD, Timothy M Pawlik, MD, MPH, PhD, FACS,
RESULTS: A total of 643 patients were included, of which 541 (84.1%) were resected with curative-intent (284 distal, 257 hilar). Perioperative mortality (4.5%) was excluded from the analysis. Median age was 67.1 and 61.6% of patients were male. Surgery consisted of bile duct resection only in 96 (17.8%), bile duct and liver resection in 215 (40%), and pancreatoduodenectomy in 227 (42.2%). Thirty-day morbidity was 64.6% (34.0% major). Median length of hospital stay (LOS) was 10 days (IQR: 7 - 15). Thirty-day readmission rate was 21.1%; in multivariate analysis, 30-day readmission was independently associated with the incidence of postoperative complications [OR¼5.7, 95% CI, (2.3 e 14.5)], specifically deep/organ space infection [OR 3.7 (1.7 e 7.9)], shorter LOS [LOS8 days, OR: 4.5, 95% CI: (2.2 e 9.1)]. CONCLUSIONS: Readmission after surgery for EHC was common as 1 in 5 patients experienced a readmission. Patients with postoperative complications, specifically deep/organ space infection, and patients discharged early were at higher risk. Strategies focusing on early postoperative clinic visit may reduce the risk of readmission.
Influence of Surgical Volume on Cost Variations for Pancreatic Surgery Howard W Nelson-Williams, MD, MPH, Faiz Gani, MBBS, Timothy M Pawlik, MD, MPH, PhD, FACS Johns Hopkins University School of Medicine, Baltimore, MD INTRODUCTION: In this era of quality improvement and cost efficiency, the economic impact of volume-driven care is understudied. The objective of this study was to assess the influence of hospital volume on inpatient cost variations after pancreatic surgery. METHODS: The Nationwide Inpatient Sample was used to identify patients undergoing elective pancreatic surgery from 2001 to 2012. Charges for inpatient care were derived from the administrative dataset and hospital cost-to-charge ratios were used to compute