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Prospective randomized controlled trial comparing laparoscopic versus open pancreaticoduodenectomy for malignant periampullary and pancreatic head lesions
Electronic Poster Abstracts Method: The desensitization (DSZ) protocol included a single dose of rituximab and total plasma exchange. Additionally, local graft infusion therapy, cyclophosphamide, or splenectomy was used for a certain time period, but this was eventually discontinued due to adverse events. Results: Total 340 cases of ABOi ALDLT were performed from November 2008 to October 2015. It accounts for 15.9% of all ADLLTs which were performed during same period. The mean age and MELD score of patients was 52.0 8.0 and 13.1 9.0, respectively. There were 4 cases (1.2%) of in-hospital mortality. The cumulative 3-year graft and patient survival rates were 88.9% and 93.3%, respectively, which were comparable to those in the ABOc group (n = 2,136, p = 0.324). There was no significant diffrences of survival outcomes in propensity-matched cohort (p = 0.631) Despite promising survival outcomes, howewver, 23 (6.7%) patients experienced antibody-mediated rejection that manifested by diffuse intrahepatic biliary stricture, with six cases requiring re-transplantation and three deaths. There was no significant statistical difference in the incidence of acute cellular rejection and surgical complication bewteen ABOi and ABOc groups. Conclusion: ABOi ALDLT is a feasible method for expanding a live liver donor pool, but the efficacy of the DSZ protocol in targeting B-cell immunity should be optimized.
PL02-02 TEN-YEAR FOLLOW UP CASECONTROL STUDY OF THE EFFECT OF PORTAL VEIN EMBOLISATION ON THE SURVIVAL OF PATIENTS WITH COLORECTAL LIVER METASTASES; THE HYPOXIA FACTOR INFLUENCE P. Siriwardana1,2, T. Luong3, J. Watkins3, H. Turley4, W. Ong5, K. Gatter4, D. Hochhauser6, A. Harris7 and B. Davidson1,8 1 Hepatopancreato Biliary Surgery Unit, Royal Free London NHS Foundation Trust, 2Division of Surgery and Interventional Sciences, University College London, 3 Department of Cellular Pathology, Royal Free London NHS Foundation Trust, 4University of Oxford, Nuffield Department of Clinical Laboratory Sciences, 5Division of Information Engineering, University of Cambridge, 6UCL Cancer Institute, University College London, 7Weatherall Institute of Molecular Medicine, Oxford University Department of Oncology, and 8Division of Surgery and Interventional Sciences, University College London, United Kingdom Introduction: PVE facilitates hepatectomy in patients with a small anticipated future liver remnant, but stimulates tumour growth. Hypoxia may mediate this increased tumour growth as Hypoxia-Inducible-Factor-1a (HIF-1a) increases angiogenesis, invasion and other Hallmarks of Cancer. This study investigates the relationship of patient survival to expression of HIF-1a and other hypoxia factors regulated in resected CRLM, in a case control study, comparing patients with and without PVE.
HPB 2016, 18 (S1), e1ee384
e3
Methods: Twenty-six patients who had PVE were compared with 25 controls matched with the number and size of metastases (tumour-burden). Immunostaining was performed on CRLM formalin-fixed-paraffinembedded sections to compare the expression of hypoxic factors regulated factors, HIF-1a and CA-9, vascular endothelial growth factor (VEGF) and a blood vessel marker, CD31, between the groups. Disease progression, liver specific recurrence and actuarial survival were recorded. Results: The clinicopathological characteristics of the cancers were comparable between the groups. The median follow-up was 115 months (range 106e124). Overall, 5 year, local hepatic recurrence-free survival and progression-free periods were poor in those patients undergoing PVE (p = 0.026, p = 0.060, p = 0.001 and p = 0.008 respectively). The expression of hypoxia markers between the groups was similar. Conclusion: This is the first long-term (>5 year) case matched series on outcome of patients with CRLM following PVE. Whilst, PVE facilitates potentially curative resection of CRLM, prognosis is less than those patients not requiring PVE. Whilst further molecular research is required to investigate the cause of tumour growth and reduced prognosis, the hepatic artery buffer response may have a role in preventing intratumoural hypoxia following PVE.
PL02-03 PROSPECTIVE RANDOMIZED CONTROLLED TRIAL COMPARING LAPAROSCOPIC VERSUS OPEN PANCREATICODUODENECTOMY FOR MALIGNANT PERIAMPULLARY AND PANCREATIC HEAD LESIONS S. Palanisamy, S. C. Sabnis, N. D. Patel, S. Gurumurthy, A. V. Natesan, N. Palanisamy, P. R. Palanivelu, R. Parthasarathi, S. Rajapandian and P. Chinnusamy Department of Minimal Access, HPB & Liver Transplantation, GEM Hospital & Research Centre, India Background: Current literature supports the use of laparoscopic pancreaticoduodenectomy (LPD) as an alternative to open pancreaticoduodenectomy (OPD) for pancreatobiliary malignancies. Studies done so far are case series and matched comparisons; a randomized trial analysing two has not been reported. Materials and method: Trial included 64 patients with resectable peri-ampullary or pancreatic head cancer, randomized by computer generated random numbers into either LPD or OPD group during September 2013 to August 2015. Sample size was 32 in each arm, assuming power of study 80% & type I error of 0.05. Primary outcome measure was hospital stay, secondary outcome measures were blood loss, operation time, pathological radicality and complication rate. Results: Mean operative time 260.2 min (11.10) in OPD, 359.4 min (13.84) in LPD (p = 0.0308). Mean blood loss 300.6 ml (46.56) in OPD, 249.8 ml (22.33) in LPD (p < 0.001). Conversion rate of 3.1%. The median length of stay in OPD was 12 days (6e30), LPD of 8 days (5e52) (p = 0.0001). Pancreatic fistula
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Electronic Poster Abstracts
18.75% in OPD; 15.60% in LPD (p = 0.314), overall complications (Clavien Dindo) 31.25% in OPD; 25% in LPD (p = 0.755) and 3.1% mortality in each arm. Mean nodes retrieved in OPD 17.00 (1.47), LPD 18.97 (1.0) with 0.95 CI, p = 0.059. Conclusion: This study establishes safety of LPD in terms of short term outcomes, complications, mortality and oncological radicality to that of OPD, has benefits of shorter hospital stay, reduced blood loss and lesser wound complications. Comparisons in terms of disease free survival and long term survival remains to be seen (NCT02081131).
PL02-04 OXYGENATED HYPOTHERMIC MACHINE PERFUSION AFTER STATIC COLD STORAGE IMPROVES ENDOTHELIAL FUNCTION OF EXTENDED CRITERIA DONOR LIVERS L. C. Burlage1, N. Karimian1, A. C. Westerkamp1, N. Visser2, S. Op den Dries1, M. E. Sutton1, A. P. M. Matton1, R. Van Rijn1, J. Adelmeijer2, A. H. S. Gouw3, T. Lisman2 and R. J. Porte1 1 Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, 2Surgical Research Laboratory, Department of Surgery, and 3 Department of Pathology, University Medical Center Groningen, Netherlands Background: Lack of oxygen and biomechanical stimulation during static cold storage (SCS) of donor livers compromises endothelial cell function. This study investigated the effect of 2 hours of end-ischemic oxygenated hypothermic machine perfusion (HMP) on endothelial cell function of extended criteria donor (ECD) livers. Method: Sixteen human livers that were declined for transplantation were transported to our center using conventional static cold storage (SCS; 4oC) and subjected to normothermic machine perfusion (NMP) to assess viability and function. Six livers underwent 2 hours oxygenated HMP (12 C) after SCS and prior to NMP. Ten control livers underwent NMP immediately after SCS. Endothelial cell function was assessed by quantification of mRNA expression encoding for transcription factor Krüppel-like-factor-2 (KLF-2), endothelial nitric oxide synthase (eNOS), and thrombomodulin (TM) using real-time PCR. Nitric oxide (NO) production (nitrite/nitrate levels) and release of thrombomodulin (TM) into the perfusion fluid were determined during NMP. Results: In livers that underwent end-ischemic HMP, mRNA expression of KLF-2 (p = 0.04), eNOS (p = 0.03) and TM (p = 0.03) increased significantly during NMP. This response was not observed in the control livers. In parallel, NO levels in the perfusate increased during NMP of livers that first underwent HMP, but not in control livers. Moreover, at the end of NMP cumulative TM release into the perfusate was significantly higher in control livers compared to livers first subjected to HMP (p = 0.03). Conclusion: A short period of 2 hours oxygenated HMP restores endothelial cell function and integrity after conventional static cold preservation and subsequent reoxygenation of ECD livers.
PL03 e “Oral Plenary 3: “Best of the Best”
PL03-01 AGE-DEPENDENT CHANGES IN LIVER FUNCTION K. P. Cieslak1, O. Baur1, R. J. Bennink2 and T. M. van Gulik1 1 Department of Surgery, and 2Department of Nuclear Medicine, Academic Medical Center, Amsterdam, Netherlands Introduction: Age itself is not considered a contraindication for high impact surgery, including major liver resections, provided that after accurate assessment the patient is found to be fit. However, the aging process of the liver and its influence on liver function remain largely unknown. The aim of this study was to evaluate age-dependent changes in total liver function using a quantitative liver function test. Methods: Between January 2005 and December 2014, 508 patients underwent 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) at our institution for the assessment of hepatic uptake function. Only patients with healthy liver parenchyma were included. Mebrofenin uptake-rate of the whole liver corrected for body surface area (cMUR) was calculated for all patients. Linear regression analysis was performed to study the relationship between age and cMUR. Results: 203/508 patients diagnosed with hepatic metastases or benign liver tumors were included, with otherwise healthy livers. The mean cMUR was 8.50 2.05%/min/ m2. In order to study changes in the cMUR, patients were divided in age-categories: [18e39], [40e49], [50e59], [60e69], and [70e79] years. The mean cMUR in these age groups was 9.36 2.37%/min/m2, 8.98 2.43%/min/m2, 8.66 1.65%/min/m2, 8.25 1.93%/min/m2 and 2 7.88 2.01%/min/m , respectively, p = 0.033. A significant negative linear correlation was found between patient’s age and cMUR (p < 0.001). Conclusion: This study shows that liver function significantly declines with age. Since the regenerative capacity of the liver correlates with liver function, these agedependent changes in liver function should be taken into account when assessing surgical risk in patients considered for resection.
PL03-02 PROPOSAL FOR A NEW T-STAGE CLASSIFICATION SYSTEM FOR DISTAL CHOLANGIOCARCINOMA: A 10INSTITUTION STUDY FROM THE U.S. EXTRAHEPATIC BILIARY MALIGNANCY CONSORTIUM L. Postlewait1, T. Pawlik2, G. Poultsides3, K. Idrees4, R. Fields5, S. Weber6, C. Scoggins7, P. Shen8, C. Schmidt9, I. Hatzaras10 and S. Maithel1 1 Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 2Division of Surgical Oncology, Department of Surgery, Johns Hopkins Hospital, 3Department of Surgery, Stanford University Medical Center, 4Division of Surgical Oncology, Department of Surgery, Vanderbilt University
HPB 2016, 18 (S1), e1ee384
PL02-02 TEN-YEAR FOLLOW UP CASECONTROL STUDY OF THE EFFECT OF PORTAL VEIN EMBOLISATION ON THE SURVIVAL OF PATIENTS WITH COLORECTAL LIVER METASTASES; THE HYPOXIA FACTOR INFLUENCE P. Siriwardana1,2, T. Luong3, J. Watkins3, H. Turley4, W. Ong5, K. Gatter4, D. Hochhauser6, A. Harris7 and B. Davidson1,8 1 Hepatopancreato Biliary Surgery Unit, Royal Free London NHS Foundation Trust, 2Division of Surgery and Interventional Sciences, University College London, 3 Department of Cellular Pathology, Royal Free London NHS Foundation Trust, 4University of Oxford, Nuffield Department of Clinical Laboratory Sciences, 5Division of Information Engineering, University of Cambridge, 6UCL Cancer Institute, University College London, 7Weatherall Institute of Molecular Medicine, Oxford University Department of Oncology, and 8Division of Surgery and Interventional Sciences, University College London, United Kingdom Introduction: PVE facilitates hepatectomy in patients with a small anticipated future liver remnant, but stimulates tumour growth. Hypoxia may mediate this increased tumour growth as Hypoxia-Inducible-Factor-1a (HIF-1a) increases angiogenesis, invasion and other Hallmarks of Cancer. This study investigates the relationship of patient survival to expression of HIF-1a and other hypoxia factors regulated in resected CRLM, in a case control study, comparing patients with and without PVE.
HPB 2016, 18 (S1), e1ee384
e3
Methods: Twenty-six patients who had PVE were compared with 25 controls matched with the number and size of metastases (tumour-burden). Immunostaining was performed on CRLM formalin-fixed-paraffinembedded sections to compare the expression of hypoxic factors regulated factors, HIF-1a and CA-9, vascular endothelial growth factor (VEGF) and a blood vessel marker, CD31, between the groups. Disease progression, liver specific recurrence and actuarial survival were recorded. Results: The clinicopathological characteristics of the cancers were comparable between the groups. The median follow-up was 115 months (range 106e124). Overall, 5 year, local hepatic recurrence-free survival and progression-free periods were poor in those patients undergoing PVE (p = 0.026, p = 0.060, p = 0.001 and p = 0.008 respectively). The expression of hypoxia markers between the groups was similar. Conclusion: This is the first long-term (>5 year) case matched series on outcome of patients with CRLM following PVE. Whilst, PVE facilitates potentially curative resection of CRLM, prognosis is less than those patients not requiring PVE. Whilst further molecular research is required to investigate the cause of tumour growth and reduced prognosis, the hepatic artery buffer response may have a role in preventing intratumoural hypoxia following PVE.
PL02-03 PROSPECTIVE RANDOMIZED CONTROLLED TRIAL COMPARING LAPAROSCOPIC VERSUS OPEN PANCREATICODUODENECTOMY FOR MALIGNANT PERIAMPULLARY AND PANCREATIC HEAD LESIONS S. Palanisamy, S. C. Sabnis, N. D. Patel, S. Gurumurthy, A. V. Natesan, N. Palanisamy, P. R. Palanivelu, R. Parthasarathi, S. Rajapandian and P. Chinnusamy Department of Minimal Access, HPB & Liver Transplantation, GEM Hospital & Research Centre, India Background: Current literature supports the use of laparoscopic pancreaticoduodenectomy (LPD) as an alternative to open pancreaticoduodenectomy (OPD) for pancreatobiliary malignancies. Studies done so far are case series and matched comparisons; a randomized trial analysing two has not been reported. Materials and method: Trial included 64 patients with resectable peri-ampullary or pancreatic head cancer, randomized by computer generated random numbers into either LPD or OPD group during September 2013 to August 2015. Sample size was 32 in each arm, assuming power of study 80% & type I error of 0.05. Primary outcome measure was hospital stay, secondary outcome measures were blood loss, operation time, pathological radicality and complication rate. Results: Mean operative time 260.2 min (11.10) in OPD, 359.4 min (13.84) in LPD (p = 0.0308). Mean blood loss 300.6 ml (46.56) in OPD, 249.8 ml (22.33) in LPD (p < 0.001). Conversion rate of 3.1%. The median length of stay in OPD was 12 days (6e30), LPD of 8 days (5e52) (p = 0.0001). Pancreatic fistula
e4
Electronic Poster Abstracts
18.75% in OPD; 15.60% in LPD (p = 0.314), overall complications (Clavien Dindo) 31.25% in OPD; 25% in LPD (p = 0.755) and 3.1% mortality in each arm. Mean nodes retrieved in OPD 17.00 (1.47), LPD 18.97 (1.0) with 0.95 CI, p = 0.059. Conclusion: This study establishes safety of LPD in terms of short term outcomes, complications, mortality and oncological radicality to that of OPD, has benefits of shorter hospital stay, reduced blood loss and lesser wound complications. Comparisons in terms of disease free survival and long term survival remains to be seen (NCT02081131).
PL02-04 OXYGENATED HYPOTHERMIC MACHINE PERFUSION AFTER STATIC COLD STORAGE IMPROVES ENDOTHELIAL FUNCTION OF EXTENDED CRITERIA DONOR LIVERS L. C. Burlage1, N. Karimian1, A. C. Westerkamp1, N. Visser2, S. Op den Dries1, M. E. Sutton1, A. P. M. Matton1, R. Van Rijn1, J. Adelmeijer2, A. H. S. Gouw3, T. Lisman2 and R. J. Porte1 1 Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, 2Surgical Research Laboratory, Department of Surgery, and 3 Department of Pathology, University Medical Center Groningen, Netherlands Background: Lack of oxygen and biomechanical stimulation during static cold storage (SCS) of donor livers compromises endothelial cell function. This study investigated the effect of 2 hours of end-ischemic oxygenated hypothermic machine perfusion (HMP) on endothelial cell function of extended criteria donor (ECD) livers. Method: Sixteen human livers that were declined for transplantation were transported to our center using conventional static cold storage (SCS; 4oC) and subjected to normothermic machine perfusion (NMP) to assess viability and function. Six livers underwent 2 hours oxygenated HMP (12 C) after SCS and prior to NMP. Ten control livers underwent NMP immediately after SCS. Endothelial cell function was assessed by quantification of mRNA expression encoding for transcription factor Krüppel-like-factor-2 (KLF-2), endothelial nitric oxide synthase (eNOS), and thrombomodulin (TM) using real-time PCR. Nitric oxide (NO) production (nitrite/nitrate levels) and release of thrombomodulin (TM) into the perfusion fluid were determined during NMP. Results: In livers that underwent end-ischemic HMP, mRNA expression of KLF-2 (p = 0.04), eNOS (p = 0.03) and TM (p = 0.03) increased significantly during NMP. This response was not observed in the control livers. In parallel, NO levels in the perfusate increased during NMP of livers that first underwent HMP, but not in control livers. Moreover, at the end of NMP cumulative TM release into the perfusate was significantly higher in control livers compared to livers first subjected to HMP (p = 0.03). Conclusion: A short period of 2 hours oxygenated HMP restores endothelial cell function and integrity after conventional static cold preservation and subsequent reoxygenation of ECD livers.
PL03 e “Oral Plenary 3: “Best of the Best”
PL03-01 AGE-DEPENDENT CHANGES IN LIVER FUNCTION K. P. Cieslak1, O. Baur1, R. J. Bennink2 and T. M. van Gulik1 1 Department of Surgery, and 2Department of Nuclear Medicine, Academic Medical Center, Amsterdam, Netherlands Introduction: Age itself is not considered a contraindication for high impact surgery, including major liver resections, provided that after accurate assessment the patient is found to be fit. However, the aging process of the liver and its influence on liver function remain largely unknown. The aim of this study was to evaluate age-dependent changes in total liver function using a quantitative liver function test. Methods: Between January 2005 and December 2014, 508 patients underwent 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) at our institution for the assessment of hepatic uptake function. Only patients with healthy liver parenchyma were included. Mebrofenin uptake-rate of the whole liver corrected for body surface area (cMUR) was calculated for all patients. Linear regression analysis was performed to study the relationship between age and cMUR. Results: 203/508 patients diagnosed with hepatic metastases or benign liver tumors were included, with otherwise healthy livers. The mean cMUR was 8.50 2.05%/min/ m2. In order to study changes in the cMUR, patients were divided in age-categories: [18e39], [40e49], [50e59], [60e69], and [70e79] years. The mean cMUR in these age groups was 9.36 2.37%/min/m2, 8.98 2.43%/min/m2, 8.66 1.65%/min/m2, 8.25 1.93%/min/m2 and 2 7.88 2.01%/min/m , respectively, p = 0.033. A significant negative linear correlation was found between patient’s age and cMUR (p < 0.001). Conclusion: This study shows that liver function significantly declines with age. Since the regenerative capacity of the liver correlates with liver function, these agedependent changes in liver function should be taken into account when assessing surgical risk in patients considered for resection.
PL03-02 PROPOSAL FOR A NEW T-STAGE CLASSIFICATION SYSTEM FOR DISTAL CHOLANGIOCARCINOMA: A 10INSTITUTION STUDY FROM THE U.S. EXTRAHEPATIC BILIARY MALIGNANCY CONSORTIUM L. Postlewait1, T. Pawlik2, G. Poultsides3, K. Idrees4, R. Fields5, S. Weber6, C. Scoggins7, P. Shen8, C. Schmidt9, I. Hatzaras10 and S. Maithel1 1 Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 2Division of Surgical Oncology, Department of Surgery, Johns Hopkins Hospital, 3Department of Surgery, Stanford University Medical Center, 4Division of Surgical Oncology, Department of Surgery, Vanderbilt University
HPB 2016, 18 (S1), e1ee384