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A single nucleotide polymorphism in the CD44 gene affects survival of pancreatic ductal adenocarcinoma
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Electronic Poster Abstracts
EP02D-109 RESULTS OF SURGICAL TREATMENT OF PANCREATIC CARCINOMA. ANALYSIS OF 118 CONSECUTIVE CASES P. Rebolledo1,2, C. Garcia1,2, A. Cancino1,2, J. Vallejos1,2, C. Benavides1,2 and C. Esperguel1,2 1 Surgery, Hospital San Borja Arriaran, and 2Surgery, University of Chile, Chile The global survival reported for pancreatic cancer is very poor. A very small proportion are undergoing curative surgery, so some authors suggest therapy should be aimed at goals other than survival. In recent times there has been an emphasis on selection of surgical candidates, adjuvant therapies have been introduced and neoadjuvant therapy protocols appear as an alternative. The aim is to show results, immediate and long term, of pancreatic cancer surgical treatment in our hospital during the 2001e2014 period. Material and methods: Retrospective case series of patients with postoperative diagnosis and / or histological diagnosis of pancreatic malignancy. Cases with “borderline” histology are excluded. Study period: January 2001e December 2014. Analysis of demographic, clinical, diagnostic, surgery performed and long-term survival . Descriptive statistical analysis. Results: The series includes 118 patients. Average age 61.7 years (range 20e82), 60 men and 58 women. Resections were performed with curative intent in 35 cases (29.6 %), thus a significant share of the series included palliative surgery (83 cases, 70.3 %). Curative surgeries include 27 pancreatoduodenectomies and 6 distal pancreatectomies with or without splenectomy. Overall survival in five years reached 16 %. For curative surgery, survival reached 24.6 % in 5 years. Only a tiny proportion of cases received adjuvant therapy. Conclusions: This series highlights the poor prognosis of this neoplasm in our environment, with low resectability and 5year survival in resected patients with curative intent. Clearly, a change is required in the management of this neoplasm, including proper case selection and multimodal therapies.
EP02D-110 ENDOVASCULAR TREATMENT OF SUPERIOR MESENTERIC ARTERY PSEUDOANEURYSM AND HEPATIC ARTERY PSEUDOANEURYSM AFTER PANCREATICODUODENECTOMY M. Ceroni1,2, G. Watkins2, P. Palavecino2 and N. Martínez2 1 Pontificia Universidad Católica de Chile, and 2Clínica Bicentenario, Chile 58 year old male patient with a history of hypertension. He underwent a pancreaticoduodenectomy for pancreatic head cancer. The patient presented abdominal pain and gastrointestinal bleeding three weeks after surgery. Gastrointestinal endoscopy failed to find the bleeding site. Abdominal CT angiography report superior mesenteric artery pseudo aneurysm of 4 centimeters, associated with hemoperitoneum, which was not possible to identify an laparotomy. The patient was referred to our centre. We performed selective embolization of the hepatic artery to the liver segment two. And
performed treatment of superior mesenteric artery pseudoaneurysm with Histoacryl. The post-procedural CT angiography showed normal flow of the superior mesenteric artery. The patient progressed in a satisfactory manner.
EP02D-111 A SINGLE NUCLEOTIDE POLYMORPHISM IN THE CD44 GENE AFFECTS SURVIVAL OF PANCREATIC DUCTAL ADENOCARCINOMA L. F. Grochola1, G. Stracquadanio2, R. Graf1, B. Vrugt1, S. Breitenstein3, P. Schraml1, R. Flury4, D. Henne-Bruns5, U. Knippschild5, P. -A. Clavien1 and G. Bond2 1 University Hospital Zurich, Switzerland, 2University of Oxford, United Kingdom, 3Cantonal Hospital of Winterthur, 4Institute of Pathology, Cantonal Hospital of Winterthur, Switzerland, and 5University Hospital Ulm, Germany Introduction: Previously, we have identified a single nucleotide polymorphism in the CD44 gene (SNPrs187115) that associates with allelic differences in cellular chemosensitivities and affects survival of soft-tissue sarcoma patients. In this report, we examine the possible role of this locus and other interacting SNPs in the survival outcomes of pancreatic ductal adenocarcinoma (PDAC). Method: 348 PDAC patients from 3 independent cohorts (Zurich, Switzerland; Ulm, Germany and The Cancer Genome Atlas (TCGA)) who underwent pancreatic resection are included into the study and their SNPrs187115 genotypes determined. In addition, we utilize a pathway-based analysis to search for interacting SNPs in the CD44 gene network that help identify patients at higher risk for tumour-related death. Furthermore, we begin to investigate the functional mechanisms that underlie the observed clinical effects. Results: In line with our previous results, the C/C-genotype of the CD44 SNP associates with a significantly worse prognosis in all three PDAC study cohorts with an up-to 2.41-fold increased relative-risk for tumour-related death (p = 0.018, Cox multivariate analysis). We demonstrate that this clinical effect can be modified by other interacting SNPs in this gene network and present early data indicating that those effects are caused by an alteration of CD44 expression by those SNPs. Conclusions: We describe for the first time the clinical and regulatory effects associated with CD44 SNPrs187115 and its interacting polymorphisms in PDAC. These observations suggest novel biomarkers for PDAC that can identify patients at higher risk for faster tumour progression and could potentially affect the treatment of this dismal disease.
EP02D-113 PASIREOTIDE FOR THE PREVENTION OF PANCREATIC FISTULAE FOLLOWING PANCREATICODUODENECTOMY: A COST-BENEFIT ANALYSIS G. Eeson1, N. Goyert2, M. Lemke3, D. Kagedan4, C. Law5, J. Hallet6, P. Karanicolas6 and N. Coburn5 1 Surgical Oncology, University of Toronto, 2Evaluative Clinical Sciences, Sunnybrook Health Sciences Centre,
HPB 2016, 18 (S1), e385ee601
Electronic Poster Abstracts
EP02D-109 RESULTS OF SURGICAL TREATMENT OF PANCREATIC CARCINOMA. ANALYSIS OF 118 CONSECUTIVE CASES P. Rebolledo1,2, C. Garcia1,2, A. Cancino1,2, J. Vallejos1,2, C. Benavides1,2 and C. Esperguel1,2 1 Surgery, Hospital San Borja Arriaran, and 2Surgery, University of Chile, Chile The global survival reported for pancreatic cancer is very poor. A very small proportion are undergoing curative surgery, so some authors suggest therapy should be aimed at goals other than survival. In recent times there has been an emphasis on selection of surgical candidates, adjuvant therapies have been introduced and neoadjuvant therapy protocols appear as an alternative. The aim is to show results, immediate and long term, of pancreatic cancer surgical treatment in our hospital during the 2001e2014 period. Material and methods: Retrospective case series of patients with postoperative diagnosis and / or histological diagnosis of pancreatic malignancy. Cases with “borderline” histology are excluded. Study period: January 2001e December 2014. Analysis of demographic, clinical, diagnostic, surgery performed and long-term survival . Descriptive statistical analysis. Results: The series includes 118 patients. Average age 61.7 years (range 20e82), 60 men and 58 women. Resections were performed with curative intent in 35 cases (29.6 %), thus a significant share of the series included palliative surgery (83 cases, 70.3 %). Curative surgeries include 27 pancreatoduodenectomies and 6 distal pancreatectomies with or without splenectomy. Overall survival in five years reached 16 %. For curative surgery, survival reached 24.6 % in 5 years. Only a tiny proportion of cases received adjuvant therapy. Conclusions: This series highlights the poor prognosis of this neoplasm in our environment, with low resectability and 5year survival in resected patients with curative intent. Clearly, a change is required in the management of this neoplasm, including proper case selection and multimodal therapies.
EP02D-110 ENDOVASCULAR TREATMENT OF SUPERIOR MESENTERIC ARTERY PSEUDOANEURYSM AND HEPATIC ARTERY PSEUDOANEURYSM AFTER PANCREATICODUODENECTOMY M. Ceroni1,2, G. Watkins2, P. Palavecino2 and N. Martínez2 1 Pontificia Universidad Católica de Chile, and 2Clínica Bicentenario, Chile 58 year old male patient with a history of hypertension. He underwent a pancreaticoduodenectomy for pancreatic head cancer. The patient presented abdominal pain and gastrointestinal bleeding three weeks after surgery. Gastrointestinal endoscopy failed to find the bleeding site. Abdominal CT angiography report superior mesenteric artery pseudo aneurysm of 4 centimeters, associated with hemoperitoneum, which was not possible to identify an laparotomy. The patient was referred to our centre. We performed selective embolization of the hepatic artery to the liver segment two. And
performed treatment of superior mesenteric artery pseudoaneurysm with Histoacryl. The post-procedural CT angiography showed normal flow of the superior mesenteric artery. The patient progressed in a satisfactory manner.
EP02D-111 A SINGLE NUCLEOTIDE POLYMORPHISM IN THE CD44 GENE AFFECTS SURVIVAL OF PANCREATIC DUCTAL ADENOCARCINOMA L. F. Grochola1, G. Stracquadanio2, R. Graf1, B. Vrugt1, S. Breitenstein3, P. Schraml1, R. Flury4, D. Henne-Bruns5, U. Knippschild5, P. -A. Clavien1 and G. Bond2 1 University Hospital Zurich, Switzerland, 2University of Oxford, United Kingdom, 3Cantonal Hospital of Winterthur, 4Institute of Pathology, Cantonal Hospital of Winterthur, Switzerland, and 5University Hospital Ulm, Germany Introduction: Previously, we have identified a single nucleotide polymorphism in the CD44 gene (SNPrs187115) that associates with allelic differences in cellular chemosensitivities and affects survival of soft-tissue sarcoma patients. In this report, we examine the possible role of this locus and other interacting SNPs in the survival outcomes of pancreatic ductal adenocarcinoma (PDAC). Method: 348 PDAC patients from 3 independent cohorts (Zurich, Switzerland; Ulm, Germany and The Cancer Genome Atlas (TCGA)) who underwent pancreatic resection are included into the study and their SNPrs187115 genotypes determined. In addition, we utilize a pathway-based analysis to search for interacting SNPs in the CD44 gene network that help identify patients at higher risk for tumour-related death. Furthermore, we begin to investigate the functional mechanisms that underlie the observed clinical effects. Results: In line with our previous results, the C/C-genotype of the CD44 SNP associates with a significantly worse prognosis in all three PDAC study cohorts with an up-to 2.41-fold increased relative-risk for tumour-related death (p = 0.018, Cox multivariate analysis). We demonstrate that this clinical effect can be modified by other interacting SNPs in this gene network and present early data indicating that those effects are caused by an alteration of CD44 expression by those SNPs. Conclusions: We describe for the first time the clinical and regulatory effects associated with CD44 SNPrs187115 and its interacting polymorphisms in PDAC. These observations suggest novel biomarkers for PDAC that can identify patients at higher risk for faster tumour progression and could potentially affect the treatment of this dismal disease.
EP02D-113 PASIREOTIDE FOR THE PREVENTION OF PANCREATIC FISTULAE FOLLOWING PANCREATICODUODENECTOMY: A COST-BENEFIT ANALYSIS G. Eeson1, N. Goyert2, M. Lemke3, D. Kagedan4, C. Law5, J. Hallet6, P. Karanicolas6 and N. Coburn5 1 Surgical Oncology, University of Toronto, 2Evaluative Clinical Sciences, Sunnybrook Health Sciences Centre,
HPB 2016, 18 (S1), e385ee601