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Central pancreatic resection: Still an uncommon (but safe) surgical option
Abstracts / Pancreatology 13 (2013) e1–e94 2 Ono Pharmaceutical Co., Ltd., Research Headquarters, Osaka, Japan Background: Chronic pancreatitis (CP) is an intractable disease with destruction of acinar and duct cells, interstitial fibrosis, and infiltration of inflammatory cells. ONO-1301, a novel sustained release prostacyclin analog, has an anti-fibrotic effect to lung, heart, kidney and liver, partly associated with induction of hepatocyte growth factor (HGF). However, its effect on CP is not clear. Aim: The aim of our study was to examine the effect of ONO-1301 on CP. Methods: CP was induced by dibutyltin dichloride (DBTC) (7mg/kg) in rats. Seven days after DBTC injection (day7), a slow release form of ONO1301(10mg/kg) or vehicle (control) was injected. At day 14 and 28, we evaluated histopathological CP score (edema, fatty change, inflammatory cells infiltration and fibrosis), and the expression of HGF, cytokines and collagen type1 in pancreas by realtime PCR. Results: Histopathological CP score was improved in the ONO-1301 treated group (1301 group) compared to control; especially, inflammatory cells infiltration at day 14 and interstitial fibrosis at day 28. HGF mRNA increased significantly after administration of ONO-1301, whereas IL-1b, IL-6, TNF-a, TGF-b, MCP-1 and collagen mRNA decreased significantly at day 14, and collagen, MCP-1 and TGF-b tended to decrease at day 28. Decreased inflammatory cytokines production and inflammatory cells infiltration could attenuate the following fibrosis in 1301 group. These findings might suggest that ONO-1301 suppressed local inflammation at early stage of CP with induction of HGF. Conclusion: ONO-1301 suppressed pancreatic fibrosis in the DBTCinduced CP model through inhibition of inflammatory cells infiltration in the early stage of CP. Similar to other organs, this effect of ONO-1301 might be associated with induction of HGF.
P177. Recurrence of pancreatic ductal adenocarcinoma after pancreaticoduodenectomy: Is there a role for loco-regional treatment? N.N. Nissen 1, V.G. Menon 1, C. Bresee 2, A. Wachsman 3, M. Friedman 3, R. Tuli 4. 1
Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA 2 Department of Biostatistics, Cedars-Sinai Medical Center, Los Angeles, CA, USA 3 Department of Radiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA 4 Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA Introduction: The majority of patients undergoing potentially curative surgery for pancreatic ductal adenocarcinoma (PDA) will face recurrence. While other types of metastatic tumors are often treated with locoregional therapy, this approach is rarely applied to metastatic PDA. We examined recurrence patterns of PDA and the potential application of locoregional treatment. Methods: Evaluation of a prospective database of patients undergoing pancreaticoduodenctomy at an academic institution by a single surgeon. Patients: Pancreaticoduodenectomy for PDA was performed in 95 patients between 2002 and 2012. Margin status was R0 in 88 (93%) and R1 in the remainder. Results: Overall median survival was 27 mo and 1 and 3 year survival was 68% and 41%. Known recurrence occurred in 44 of 64 patients (69%) at a median of 20.9 months, while the status of 31 patients was unknown. The most common site of initial recurrence was liver (n¼19, median 9.2 mo post-surgery), followed by local recurrence (n¼15; median 18.7 mo) and lung (n¼5; median 5.2 mo). Patients with R0 margin vs R1 recurred at a median 21 vs 5 mo. In our series 6 patients (5/6 treated in the last 2 years) underwent locoregional treatment of recurrent disease, including liver resection (n¼2), stereotactic radiotherapy (n¼2), hepatic ablation (n¼1) or radioembolization (n¼1). All 6 patients treated with loco-regional therapy are alive at a median of 15.6 mo after recurrence and a median of 25.3 mo since initial surgery.
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Summary: The initial site of recurrent PDA after pancreaticoduodenectomy is usually liver, and the major risk factor for recurrence is the margin status at resection. Loco-regional modalities for the treatment of recurrent PDA hold promise in select patients. The tendency to utilize locoregional therapy for recurrent PDA is increasing and warrants continued consideration.
P178. Central pancreatic resection: Still an uncommon (but safe) surgical option N.N. Nissen, V.G. Menon, V.C. Puri, A.A. Annamalai. Hepatobiliary and Pancreatic Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA Introduction: Central pancreatectomy (CP) is an uncommon technique used to treat select pancreatic pathology. We evaluated the utility and safety of CP over a 10 year time span at a single institution. Methods: Review of prospective database from 2003-2012. CP comprised 9% of all pancreatic resections during this period (total of 310). Results: Twenty-nine patients underwent CP for diagnoses including neuroendocrine tumor (n¼12), cystic neoplasm (n¼9) and benign stricture (n¼8). Distal pancreatic continuity was established by pancreaticogastrostomy (n¼7), pancreaticojejunostomy (n¼12), dual pancreaticoenterostomy (n¼9) or primary pancreatico-pancreatostomy (n¼1). Major complications were limited to 4 patients (14%) who required re-laparotomy or percutaneous drainage. Five patients (17%) developed postoperative pancreatic fistulae, of which 3 (10%) were ISGPF grade B/C. There was no peri-operative mortality. At mean follow-up of 29 months, no patients have developed recurrent tumor. Two patients (7%) developed diabetes and no patient has exocrine insufficiency. The frequency of CP has remained constant over the study time period, but patients operated in the more recent 5-year period were more likely to have more proximal pathology (pancreatic head or neck) and to undergo dual pancreatic anastomosis. Conclusion: Central pancreatectomy is a safe and valuable option for management of select proximal pancreatic pathology and is associated with a low rate of long term endocrine or exocrine insufficiency. Pancreatic fistula and surgical complication rates are significant but not prohibitive. Careful patient selection is essential. In this series there is a trend towards treating more proximal pancreatic pathology with CP and more common use of novel reconstruction techniques.
P179. Unsaturated-triglyceride toxicity to pancreatic acinar cells is mediated by lipolysis P. Noel 1, R. Cline 1, C. Durgampudi 2, C. Acharya 2, D. Jaligama 2, V. Singh 1. 1
Department of Medicine, University of Pittsburgh, PA, USA UPMC Passavant, University of Pittsburgh, PA, USA Background and aims: Hypertriglyceridemia is associated with severe acute pancreatitis (SAP). Additionally, unsaturated fatty acids (UFAs), are enriched in human SAP debridement fluid, and cause acinar necrosis (Sci Transl Med. 2011 Nov 2;3(107):107ra110). Interestingly, the effect of generating equimolar amounts of saturated fatty acids (SFAs) or UFAs from triglyceride precursors on acinar cells is unknown. Here we aimed to determine the effect of unsaturated triglycerides (UTGs) and saturated triglycerides (STGs) on acinar cells. Methods: Glyceryl tri-linoleate (GTL) or glyceryl tri-palmitate (GTP) were incubated with acinar cells at varying concentrations (150uM to 3.0 mM), with or without the lipase inhibitor orlistat. Lipolysis was measured by the generation of glycerol and fatty acids. Cell viability was determined by LDH leakage, propidium-iodide (PI) uptake and trypan blue staining. Mode of cell death was determined by cytochrome-C leakage, ATP levels, active caspase-3 and LC3BII Formation. 2
P177. Recurrence of pancreatic ductal adenocarcinoma after pancreaticoduodenectomy: Is there a role for loco-regional treatment? N.N. Nissen 1, V.G. Menon 1, C. Bresee 2, A. Wachsman 3, M. Friedman 3, R. Tuli 4. 1
Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA 2 Department of Biostatistics, Cedars-Sinai Medical Center, Los Angeles, CA, USA 3 Department of Radiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA 4 Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA Introduction: The majority of patients undergoing potentially curative surgery for pancreatic ductal adenocarcinoma (PDA) will face recurrence. While other types of metastatic tumors are often treated with locoregional therapy, this approach is rarely applied to metastatic PDA. We examined recurrence patterns of PDA and the potential application of locoregional treatment. Methods: Evaluation of a prospective database of patients undergoing pancreaticoduodenctomy at an academic institution by a single surgeon. Patients: Pancreaticoduodenectomy for PDA was performed in 95 patients between 2002 and 2012. Margin status was R0 in 88 (93%) and R1 in the remainder. Results: Overall median survival was 27 mo and 1 and 3 year survival was 68% and 41%. Known recurrence occurred in 44 of 64 patients (69%) at a median of 20.9 months, while the status of 31 patients was unknown. The most common site of initial recurrence was liver (n¼19, median 9.2 mo post-surgery), followed by local recurrence (n¼15; median 18.7 mo) and lung (n¼5; median 5.2 mo). Patients with R0 margin vs R1 recurred at a median 21 vs 5 mo. In our series 6 patients (5/6 treated in the last 2 years) underwent locoregional treatment of recurrent disease, including liver resection (n¼2), stereotactic radiotherapy (n¼2), hepatic ablation (n¼1) or radioembolization (n¼1). All 6 patients treated with loco-regional therapy are alive at a median of 15.6 mo after recurrence and a median of 25.3 mo since initial surgery.
e61
Summary: The initial site of recurrent PDA after pancreaticoduodenectomy is usually liver, and the major risk factor for recurrence is the margin status at resection. Loco-regional modalities for the treatment of recurrent PDA hold promise in select patients. The tendency to utilize locoregional therapy for recurrent PDA is increasing and warrants continued consideration.
P178. Central pancreatic resection: Still an uncommon (but safe) surgical option N.N. Nissen, V.G. Menon, V.C. Puri, A.A. Annamalai. Hepatobiliary and Pancreatic Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA Introduction: Central pancreatectomy (CP) is an uncommon technique used to treat select pancreatic pathology. We evaluated the utility and safety of CP over a 10 year time span at a single institution. Methods: Review of prospective database from 2003-2012. CP comprised 9% of all pancreatic resections during this period (total of 310). Results: Twenty-nine patients underwent CP for diagnoses including neuroendocrine tumor (n¼12), cystic neoplasm (n¼9) and benign stricture (n¼8). Distal pancreatic continuity was established by pancreaticogastrostomy (n¼7), pancreaticojejunostomy (n¼12), dual pancreaticoenterostomy (n¼9) or primary pancreatico-pancreatostomy (n¼1). Major complications were limited to 4 patients (14%) who required re-laparotomy or percutaneous drainage. Five patients (17%) developed postoperative pancreatic fistulae, of which 3 (10%) were ISGPF grade B/C. There was no peri-operative mortality. At mean follow-up of 29 months, no patients have developed recurrent tumor. Two patients (7%) developed diabetes and no patient has exocrine insufficiency. The frequency of CP has remained constant over the study time period, but patients operated in the more recent 5-year period were more likely to have more proximal pathology (pancreatic head or neck) and to undergo dual pancreatic anastomosis. Conclusion: Central pancreatectomy is a safe and valuable option for management of select proximal pancreatic pathology and is associated with a low rate of long term endocrine or exocrine insufficiency. Pancreatic fistula and surgical complication rates are significant but not prohibitive. Careful patient selection is essential. In this series there is a trend towards treating more proximal pancreatic pathology with CP and more common use of novel reconstruction techniques.
P179. Unsaturated-triglyceride toxicity to pancreatic acinar cells is mediated by lipolysis P. Noel 1, R. Cline 1, C. Durgampudi 2, C. Acharya 2, D. Jaligama 2, V. Singh 1. 1
Department of Medicine, University of Pittsburgh, PA, USA UPMC Passavant, University of Pittsburgh, PA, USA Background and aims: Hypertriglyceridemia is associated with severe acute pancreatitis (SAP). Additionally, unsaturated fatty acids (UFAs), are enriched in human SAP debridement fluid, and cause acinar necrosis (Sci Transl Med. 2011 Nov 2;3(107):107ra110). Interestingly, the effect of generating equimolar amounts of saturated fatty acids (SFAs) or UFAs from triglyceride precursors on acinar cells is unknown. Here we aimed to determine the effect of unsaturated triglycerides (UTGs) and saturated triglycerides (STGs) on acinar cells. Methods: Glyceryl tri-linoleate (GTL) or glyceryl tri-palmitate (GTP) were incubated with acinar cells at varying concentrations (150uM to 3.0 mM), with or without the lipase inhibitor orlistat. Lipolysis was measured by the generation of glycerol and fatty acids. Cell viability was determined by LDH leakage, propidium-iodide (PI) uptake and trypan blue staining. Mode of cell death was determined by cytochrome-C leakage, ATP levels, active caspase-3 and LC3BII Formation. 2