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Management of solitary recurrent HCC: Is re-resection justified for those with adverse prognostic factors?
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Electronic Poster Abstracts
FP05-02 A REDOX-SENSITIVE, OLIGOPEPTIDEGUIDED, SELF-ASSEMBLING, AND EFFICIENCY-ENHANCED (ROSE) SYSTEM FOR FUNCTIONAL DELIVERY OF MICRORNA THERAPEUTICS FOR TREATMENT OF HEPATOCELLULAR CARCINOMA Q. Hu1,2, K. Wang2, X. Sun1,3, Y. Li2, T. Liang1 and G. Tang2 1 Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 2Institute of Chemistry Biology and Pharmaceutical Chemistry, Zhejiang University, and 3Department of General Surgery, Huzhou Central Hospital, China Introduction: Lack of efficient adjuvant therapy contributes to a high incidence of recurrence and metastasis of hepatocellular carcinoma (HCC). A novel therapeutic is required for postoperatively prevention and adjuvant treatment of HCC. Methods: We developed a polymer-based nanosystem (ROSE) for functional gene therapy by synthesizing a supramolecular complex self-assembled from polyethylenimine-cyclodextrin polycations (PEI-CD) and functional polyethylene-glycol (PEG) moieties. The designed nanosystem contains redox-sensitive disulfide bonds and tumor targeting oligopeptides. Introducing tumor suppressor microRNA-34a (miR-34a) therapeutics to complex with the nanosystem, we studied nanocomplex stability, gene transfection ability, redox-responsive release behavior, and tumor specificity of the delivery system in both LM3 HCC cell lines and tumor-bearing mice model. We also applied ROSE/miR34a to treat HCC in vitro and in vivo. Results: The ROSE system condensing miR-34a therapeutics became ROSE/miR-34a nanoparticles that could facilitate gene transfection in HCC cells with satisfied stability and efficiency, possibly due to proton sponge effect by polycations, PEGlyation protection, and controlled release by breakdown of disulfide bonds. Meanwhile, modification with a targeting oligopeptide SP94 in ROSE/ miR-34a enables approximately 1000-fold affinity for HCC than hepatocytes in vitro and greater HCC specificity in vivo. Furthermore, ROSE/miR-34a nanoparticles could significantly inhibit LM3 cell proliferation and in vivo tumor growth, representing a notable effect improvement over conventional gene delivery strategies. Conclusion: We successfully developed a redox-sensitive, oligopeptide-guided, self-assembling, and efficiencyenhanced nanosystem that functionally promotes miR-34a transfection with enhanced anti-HCC effect. ROSE/miR-34a therefore is a potential therapeutic agent in future adjuvant therapy for HCC treatment.
[Figure]
FP05-03 COMPARISON OF UICC/AJCC PN STAGE, NUMBER OF METASTATIC LYMPH NODES, LYMPH NODE RATIO AND LOG ODDS OF METASTATIC LYMPH NODE IN PATIENTS WITH PERIHILAR CHOLANGIOCARCINOMA S. Conci, A. Ruzzenente, F. Bertuzzo, T. Campagnaro, A. Dorna, M. De Angelis, M. Piccino and A. Guglielmi Department of Surgery, University of Verona, Italy Background and aims: Lymph-node (LN) metastases are a strong predictor of poor prognosis after surgery with curative intent in patients with perihilar cholangiocarcinoma (PCC). The aims of the study were to compare the prognostic performances of UICC/AJCC pN stage, number of metastatic LN (MLN), LN ratio (LNR), and log odds of metastatic LN (LODDS) staging methods in patients with PCC. Methods: A retrospective analysis of clinicopathological features of 99 patients with PCC underwent surgery with curative intent was carried out. The Kaplan-Meier method and Cox proportional hazards regression models were used to analyze survival and compare the different stratification system. Results: LN dissection was performed in 92.9% of the patients (n = 92). Forty-nine patients (49.5%) had no LN metastases while 43 patients (43.4%) had LN metastases. The median overall survival for the study population was 34.9 months, with a 3-years and 5-years overall survival rate of 49.5% and 23.7%, respectively. Patients with LN metastases (AJCC/UICC N stage) had an increased risk of death (HR 1.74, 95% C.I. 1.21-2.53; p = 0.003). When assessed using categorical values MLN (HR 2.23, 95% C.I. 1.49e3.34; p < 0.001), LNR (HR 2.03, 95% C.I. 1.37e 3.01; p < 0.001) and LODDS (HR 3.41, 95% C.I. 1.79e 6.45; p < 0.001,) showed a better prognostic performance than AJCC/UICC N stage. Likelihood log rank of UICC/ AJCC N stage, MLN, LNR and LODDS resulted 388.209, 381.890, 384.547 and 382,213, respectively. Conclusion: MLN, LNR and LODDS better stratified prognostic performance than the AJCC 7th edition staging system.
FP05-04 MANAGEMENT OF SOLITARY RECURRENT HCC: IS RE-RESECTION JUSTIFIED FOR THOSE WITH ADVERSE PROGNOSTIC FACTORS? W. C. Dai, T. T. Cheung, K. S. H. Chok, A. C. Y. Chan, S. C. Chan, R. T. P. Poon and C. M. Lo Surgery, University of Hong Kong, Hong Kong Introduction: Post-resection recurrence for HCC is common and there is a lack of convincing evidence regarding its treatment modalities. Method: Retrospective study of 1445 HCC patients who underwent initial liver resection at Queen Mary Hospital, Hong Kong was performed. The survival after recurrence after re-resection, TACE or RFA were analyzed. Results: 351 patients (24.2%) developed solitary intrahepatic recurrence. Re-resection achieved a significant
HPB 2016, 18 (S1), e1ee384
Electronic Poster Abstracts better overall survival after recurrence compared with TACE or RFA group, with 5-year survival after recurrence of 55.2%, 36.4% and 34.4% respectively (p = 0.005).
Figure 1. Overall survival after solitary recurrence for the re-resection, RFA and TACE group.
For those with multifocal HCC in the primary resection, re-resection achieved a significantly better overall survival after recurrence (53.3%, 30.2% and 16.1%, p = 0.021). For recurrence within 2 years of primary resection, re-resection showed a trend of better survival compared with the RFA or TACE group with 5 year-survival after recurrence to be 48.8%, 30% and 23.5% (p = 0.095). Similar finding was also found for those who has advanced stage (UICC stage 3) in the primary resection, with 5-year overall survival after recurrence to be 50%, 23.8% and 22% (p = 0.115). By multivariate analysis, microvascular invasion (risk ratio 1.59; 95% CI 1.15e2.21; P = 0.005) and time to recurrence (risk ratio 0.98; 95% CI 0.968e0.993; P = 0.002) were identified as independent risk factors for overall survival after recurrence. Conclusion: Re-resection achieved a significantly better overall survival after solitary recurrence. For those with multifocal tumour or advanced stage in the primary resection or early recurrence, re-resection is associated with a trend of better survival compared with RFA or TACE.
FP05-05 LAPAROSCOPIC VERSUS OPEN LIVER RESECTION FOR SOLITARY HEPATOCELLULAR CARCINOMA LESS THAN 5 CM IN CHILD A CIRRHOTIC PATIENTS: A PROSPECTIVE RANDOMIZED STUDY A. Elgendi1, M. Elshafei2, S. Elgendi3, E. Bedewy4 and A. Shawky1 1 Surgery, 2Radiology, 3Pathology, and 4Hepatology, Alexandria University, Egypt Introduction: Current literature is lacking level 1 evidence for surgical and oncologic outcomes of HCC undergoing HPB 2016, 18 (S1), e1ee384
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laparoscopic versus open hepatectomy. Aim was to compare feasibility, safety, surgical and oncologic efficiency of laparoscopic versus open liver resection in management of solitary small ( < 5cm) peripheral HCC in Child A cirrhotic patients. Methods: Patients were randomly assigned to either open liver resection group (OLR: 25 patients) or laparoscopic liver resection group (LRR: 25 patients). All were treated with curative intent aiming at achieving R0 resection using radiofrequency-assisted technique. Results: LLR group had significantly less operative time (120.32 21.58 vs 146.80 16.59 min, p < 0.001), significantly shorter duration of hospital stay (2.40 0.58 vs 4.28 0.79 days p < 0.001), but similar overall complications (25 vs 28%, p = 0.02). LLR had comparative resection time (66.56 23.80 vs 59.56 14.74 min, p = 0.218), amount of blood loss (250 vs 230 ml, p = 0.915), transfusion rate (p = 1.00), R0 resection rate when compared with OLR. After median follow-up of 34.43 (31.67e38.60) months, LLR achieved same adequate oncological outcome of OLR, no local recurrence and no significant difference in early recurrence and number of de novo lesions (p = 00.49). 1year and 3-year DFS rates 88% and 59%, in the LLR comparable to corresponding rates of 84% and 54% in OLR (p = 00.9). Conclusion: LLR for solitary small HCC in cirrhotic is superior to the OLR in terms of its shorter operative time and duration of hospital stay and does not compromise the oncological outcomes.
FP06 e Free Papers 6 (long oral) e Biliary 1
FP06-02 CHOLECYSTOCHOLEDOCHOLITHIASIS TREATED BY SIMULTANEOUS LAPAROENDOSCOPIC RENDEZVOUS H. Richter1, C. Harz1, H. De La Fuente2, M. Buchheister2, E. Waugh2, L. Montero1 and C. Navarrete2 1 Cirugía Endoscópica, and 2Cirugía, Clínica Santa María, Chile Introduction: Intraoperative ERCP (IO-ERCP) with laparoendoscopic rendezvous is a technique that has been gaining wide acceptance among surgical multidisciplinary teams. It’s a patient tailored treatment, performed only when needed. And it seems to lower the rate of complications of ERCP, because “over the wire” direct canulation. Patients and methods: This is a descriptive and prospective study of a cohort of 200 consecutive patients treated at our institution between 2008 and 2014. We treated elective and emergency patients with cholelithiasis and simultaneous choledocolithiasis, diagnosed by ultrasound, MRI or intraoperative cholangiography (IOC). All were treated by laparoscopic cholecystectomy and IOERCP when needed. Results: We treated 200 patients, (121 women and 79 men) mean age 47,5 (16e90). Rendezvous was achieved in 184 (92%) of the patients. The rate of conversion to open surgery was 2% (4 patients). The principal complications of ERCP were 2 post sphyncterotomy bleeding, 1 mild acute pancreatitis. The laparoscopic complications were one hemoperitoneum, one partial bile duct injury. There were
Electronic Poster Abstracts
FP05-02 A REDOX-SENSITIVE, OLIGOPEPTIDEGUIDED, SELF-ASSEMBLING, AND EFFICIENCY-ENHANCED (ROSE) SYSTEM FOR FUNCTIONAL DELIVERY OF MICRORNA THERAPEUTICS FOR TREATMENT OF HEPATOCELLULAR CARCINOMA Q. Hu1,2, K. Wang2, X. Sun1,3, Y. Li2, T. Liang1 and G. Tang2 1 Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 2Institute of Chemistry Biology and Pharmaceutical Chemistry, Zhejiang University, and 3Department of General Surgery, Huzhou Central Hospital, China Introduction: Lack of efficient adjuvant therapy contributes to a high incidence of recurrence and metastasis of hepatocellular carcinoma (HCC). A novel therapeutic is required for postoperatively prevention and adjuvant treatment of HCC. Methods: We developed a polymer-based nanosystem (ROSE) for functional gene therapy by synthesizing a supramolecular complex self-assembled from polyethylenimine-cyclodextrin polycations (PEI-CD) and functional polyethylene-glycol (PEG) moieties. The designed nanosystem contains redox-sensitive disulfide bonds and tumor targeting oligopeptides. Introducing tumor suppressor microRNA-34a (miR-34a) therapeutics to complex with the nanosystem, we studied nanocomplex stability, gene transfection ability, redox-responsive release behavior, and tumor specificity of the delivery system in both LM3 HCC cell lines and tumor-bearing mice model. We also applied ROSE/miR34a to treat HCC in vitro and in vivo. Results: The ROSE system condensing miR-34a therapeutics became ROSE/miR-34a nanoparticles that could facilitate gene transfection in HCC cells with satisfied stability and efficiency, possibly due to proton sponge effect by polycations, PEGlyation protection, and controlled release by breakdown of disulfide bonds. Meanwhile, modification with a targeting oligopeptide SP94 in ROSE/ miR-34a enables approximately 1000-fold affinity for HCC than hepatocytes in vitro and greater HCC specificity in vivo. Furthermore, ROSE/miR-34a nanoparticles could significantly inhibit LM3 cell proliferation and in vivo tumor growth, representing a notable effect improvement over conventional gene delivery strategies. Conclusion: We successfully developed a redox-sensitive, oligopeptide-guided, self-assembling, and efficiencyenhanced nanosystem that functionally promotes miR-34a transfection with enhanced anti-HCC effect. ROSE/miR-34a therefore is a potential therapeutic agent in future adjuvant therapy for HCC treatment.
[Figure]
FP05-03 COMPARISON OF UICC/AJCC PN STAGE, NUMBER OF METASTATIC LYMPH NODES, LYMPH NODE RATIO AND LOG ODDS OF METASTATIC LYMPH NODE IN PATIENTS WITH PERIHILAR CHOLANGIOCARCINOMA S. Conci, A. Ruzzenente, F. Bertuzzo, T. Campagnaro, A. Dorna, M. De Angelis, M. Piccino and A. Guglielmi Department of Surgery, University of Verona, Italy Background and aims: Lymph-node (LN) metastases are a strong predictor of poor prognosis after surgery with curative intent in patients with perihilar cholangiocarcinoma (PCC). The aims of the study were to compare the prognostic performances of UICC/AJCC pN stage, number of metastatic LN (MLN), LN ratio (LNR), and log odds of metastatic LN (LODDS) staging methods in patients with PCC. Methods: A retrospective analysis of clinicopathological features of 99 patients with PCC underwent surgery with curative intent was carried out. The Kaplan-Meier method and Cox proportional hazards regression models were used to analyze survival and compare the different stratification system. Results: LN dissection was performed in 92.9% of the patients (n = 92). Forty-nine patients (49.5%) had no LN metastases while 43 patients (43.4%) had LN metastases. The median overall survival for the study population was 34.9 months, with a 3-years and 5-years overall survival rate of 49.5% and 23.7%, respectively. Patients with LN metastases (AJCC/UICC N stage) had an increased risk of death (HR 1.74, 95% C.I. 1.21-2.53; p = 0.003). When assessed using categorical values MLN (HR 2.23, 95% C.I. 1.49e3.34; p < 0.001), LNR (HR 2.03, 95% C.I. 1.37e 3.01; p < 0.001) and LODDS (HR 3.41, 95% C.I. 1.79e 6.45; p < 0.001,) showed a better prognostic performance than AJCC/UICC N stage. Likelihood log rank of UICC/ AJCC N stage, MLN, LNR and LODDS resulted 388.209, 381.890, 384.547 and 382,213, respectively. Conclusion: MLN, LNR and LODDS better stratified prognostic performance than the AJCC 7th edition staging system.
FP05-04 MANAGEMENT OF SOLITARY RECURRENT HCC: IS RE-RESECTION JUSTIFIED FOR THOSE WITH ADVERSE PROGNOSTIC FACTORS? W. C. Dai, T. T. Cheung, K. S. H. Chok, A. C. Y. Chan, S. C. Chan, R. T. P. Poon and C. M. Lo Surgery, University of Hong Kong, Hong Kong Introduction: Post-resection recurrence for HCC is common and there is a lack of convincing evidence regarding its treatment modalities. Method: Retrospective study of 1445 HCC patients who underwent initial liver resection at Queen Mary Hospital, Hong Kong was performed. The survival after recurrence after re-resection, TACE or RFA were analyzed. Results: 351 patients (24.2%) developed solitary intrahepatic recurrence. Re-resection achieved a significant
HPB 2016, 18 (S1), e1ee384
Electronic Poster Abstracts better overall survival after recurrence compared with TACE or RFA group, with 5-year survival after recurrence of 55.2%, 36.4% and 34.4% respectively (p = 0.005).
Figure 1. Overall survival after solitary recurrence for the re-resection, RFA and TACE group.
For those with multifocal HCC in the primary resection, re-resection achieved a significantly better overall survival after recurrence (53.3%, 30.2% and 16.1%, p = 0.021). For recurrence within 2 years of primary resection, re-resection showed a trend of better survival compared with the RFA or TACE group with 5 year-survival after recurrence to be 48.8%, 30% and 23.5% (p = 0.095). Similar finding was also found for those who has advanced stage (UICC stage 3) in the primary resection, with 5-year overall survival after recurrence to be 50%, 23.8% and 22% (p = 0.115). By multivariate analysis, microvascular invasion (risk ratio 1.59; 95% CI 1.15e2.21; P = 0.005) and time to recurrence (risk ratio 0.98; 95% CI 0.968e0.993; P = 0.002) were identified as independent risk factors for overall survival after recurrence. Conclusion: Re-resection achieved a significantly better overall survival after solitary recurrence. For those with multifocal tumour or advanced stage in the primary resection or early recurrence, re-resection is associated with a trend of better survival compared with RFA or TACE.
FP05-05 LAPAROSCOPIC VERSUS OPEN LIVER RESECTION FOR SOLITARY HEPATOCELLULAR CARCINOMA LESS THAN 5 CM IN CHILD A CIRRHOTIC PATIENTS: A PROSPECTIVE RANDOMIZED STUDY A. Elgendi1, M. Elshafei2, S. Elgendi3, E. Bedewy4 and A. Shawky1 1 Surgery, 2Radiology, 3Pathology, and 4Hepatology, Alexandria University, Egypt Introduction: Current literature is lacking level 1 evidence for surgical and oncologic outcomes of HCC undergoing HPB 2016, 18 (S1), e1ee384
e25
laparoscopic versus open hepatectomy. Aim was to compare feasibility, safety, surgical and oncologic efficiency of laparoscopic versus open liver resection in management of solitary small ( < 5cm) peripheral HCC in Child A cirrhotic patients. Methods: Patients were randomly assigned to either open liver resection group (OLR: 25 patients) or laparoscopic liver resection group (LRR: 25 patients). All were treated with curative intent aiming at achieving R0 resection using radiofrequency-assisted technique. Results: LLR group had significantly less operative time (120.32 21.58 vs 146.80 16.59 min, p < 0.001), significantly shorter duration of hospital stay (2.40 0.58 vs 4.28 0.79 days p < 0.001), but similar overall complications (25 vs 28%, p = 0.02). LLR had comparative resection time (66.56 23.80 vs 59.56 14.74 min, p = 0.218), amount of blood loss (250 vs 230 ml, p = 0.915), transfusion rate (p = 1.00), R0 resection rate when compared with OLR. After median follow-up of 34.43 (31.67e38.60) months, LLR achieved same adequate oncological outcome of OLR, no local recurrence and no significant difference in early recurrence and number of de novo lesions (p = 00.49). 1year and 3-year DFS rates 88% and 59%, in the LLR comparable to corresponding rates of 84% and 54% in OLR (p = 00.9). Conclusion: LLR for solitary small HCC in cirrhotic is superior to the OLR in terms of its shorter operative time and duration of hospital stay and does not compromise the oncological outcomes.
FP06 e Free Papers 6 (long oral) e Biliary 1
FP06-02 CHOLECYSTOCHOLEDOCHOLITHIASIS TREATED BY SIMULTANEOUS LAPAROENDOSCOPIC RENDEZVOUS H. Richter1, C. Harz1, H. De La Fuente2, M. Buchheister2, E. Waugh2, L. Montero1 and C. Navarrete2 1 Cirugía Endoscópica, and 2Cirugía, Clínica Santa María, Chile Introduction: Intraoperative ERCP (IO-ERCP) with laparoendoscopic rendezvous is a technique that has been gaining wide acceptance among surgical multidisciplinary teams. It’s a patient tailored treatment, performed only when needed. And it seems to lower the rate of complications of ERCP, because “over the wire” direct canulation. Patients and methods: This is a descriptive and prospective study of a cohort of 200 consecutive patients treated at our institution between 2008 and 2014. We treated elective and emergency patients with cholelithiasis and simultaneous choledocolithiasis, diagnosed by ultrasound, MRI or intraoperative cholangiography (IOC). All were treated by laparoscopic cholecystectomy and IOERCP when needed. Results: We treated 200 patients, (121 women and 79 men) mean age 47,5 (16e90). Rendezvous was achieved in 184 (92%) of the patients. The rate of conversion to open surgery was 2% (4 patients). The principal complications of ERCP were 2 post sphyncterotomy bleeding, 1 mild acute pancreatitis. The laparoscopic complications were one hemoperitoneum, one partial bile duct injury. There were