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Biliary Tract Cancer Patient Selection for Adjuvant Chemotherapy and Radiation: A National Cancer Database Analysis
HEPATOBILIARY AND PANCREAS METHODS: An anonymous online survey was distributed to members of the Americas Hepato-Pancreato-Biliary Association. Questions regarding new HPB patients focused on: time devoted to patient counseling, use of techniques for evaluating and enhancing patient understanding, perception of level of education, and estimated literacy.
Depleted Tumor Suppressor miR-107 in Plasma Relates to Tumor Progression and Is a Novel Therapeutic Target in Pancreatic Cancer Taisuke Imamura, MD, Shuhei Komatsu, MD, PhD, FACS, Daisuke Ichikawa, MD, Wataru Okajima, MD, PhD, Takuma Ohashi, Jun Kiuchi, MD, Keiji Nishibeppu, Hisashi Ikoma, Hiroki Taniguchi, MD, PhD, Eigo Otsuji Kyoto Prefectural University of Medicne, Kyoto Second Red Cross Hospital, Kyoto, Japan INTRODUCTION: This study explored decreased tumor suppressor microRNA (miRNA) plasma levels in pancreatic cancer (PCa) patients to clarify their potential as novel biomarkers and therapeutic targets. METHODS: We used the TorayÒ 3D-Gene microRNA arraybased approach to select candidates by comparing plasma levels between PCa patients and healthy volunteers. RESULTS: Six down-regulated miRNAs (miR-107, miR-126, miR-451, miR-145, miR-491-5p, and miR-146b-5p) were selected. Small- and large-scale analyses using samples from 100 PCa patients and 80 healthy volunteers revealed that miR-107 was the most down-regulated miRNA in PCa patients compared with healthy volunteers (p< 0.0001; area under the receiver-operating characteristic curve, 0.851). A low miR-107 plasma level was significantly associated with advanced T stage, N stage, and liver metastasis and was an independent factor predicting poor prognosis in PCa patients (p ¼ 0.012; hazard ratio, 4.56; 95% CI: 1.3817.4). miR-107 overexpression in PCa cells induced G1/S arrest with the production of p21 (targeting Notch2) and inhibited cell proliferation. In vivo, the restoration and maintenance of the miR-107 plasma level significantly inhibited tumor progression in mice. CONCLUSIONS: Depletion of the tumor suppressor miRNA-107 in plasma relates to tumor progression and poor outcomes. The restoration of the plasma miR-107 level might be a novel anticancer treatment strategy for PCa. Assessment of Patient Health literacy: A International Survey of Hepato-PancreatoBiliary (HPB) Surgeons Manuel Castillo-Angeles, MD, MPH, Rodrigo Calvillo-Ortiz, MD, Ammara A Watkins, MD, MPH, Danilo Acosta, MD, Carlos Chan, MD, Charles M Vollmer, Jr, MD, Tara S Kent, MD, FACS Beth Israel Deaconess Medical Center, Boston, MA
RESULTS: There were 149 survey participants (10.03 % response rate). A total of 87.2% were male and 66.7% were US surgeons. Patient literacy was most frequently assessed by general impression (89.2%) and by asking patients about employment (60.4%); 9.3% did not assess literacy. Forty-one percent of surgeons reported spending 30 minutes or less counseling new patients, and 13.4% reported spending more than 45 minutes. Pictures/diagrams (94.6%) and lay terminology (92.6%) were the most common patient education techniques, whereas only 6.7% used teach-back methods. Level of education and reading level were perceived by HPB surgeons to be greater than population-based data. US surgeons spent more time counseling patients when compared with non-US-based surgeons (p¼0.03). CONCLUSIONS: Even though HPB surgeons devote significant time to patient counseling, validated techniques to identify low literacy patients are infrequently used. Increased use of such techniques may contribute to improved patient participation, compliance, satisfaction, and overall health outcomes, and warrants further study. Biliary Tract Cancer Patient Selection for Adjuvant Chemotherapy and Radiation: A National Cancer Database Analysis Ioannis T Konstantinidis, MD, Zeljka Jutric, Philip HG Ituarte, PhD, Susanne G Warner, Laleh G Melstrom, MD, FACS, Gagandeep Singh, MD, Yuman Fong, MD, FACS City of Hope National Medical Center, Duarte, CA INTRODUCTION: Chemotherapy is associated with prolongation of survival for advanced biliary cancer. The role of adjuvant chemotherapy and radiation after resection with curative intent is not well established. METHODS: Data from 12,711 patients with biliary tract adenocarcinoma from the National Cancer Database (gallbladder (GBC): 6713, intrahepatic cholangiocarcinoma (IHC): 1923, extrahepatic cholangiocarcinoma (EHC): 4075) who underwent resection with microscopically negative (R0) or positive (R1) margins between 2004 and 2013 and had at least 3 months of followup were analyzed. Pathologic M1 cases were excluded.
INTRODUCTION: The ability to access, process and comprehend information about health care, known as functional health literacy, has been shown to improve outcomes. Our aim was to evaluate surgeons’ recognition of the role of health literacy in patient decision-making and understanding, and what techniques surgeons use to assess and accommodate patients’ needs.
RESULTS: The majority of resections were R0 for all disease sites (GBC: 84.3%, IHC: 83.7%, EHC: 80.4%). Lymph nodes were evaluated in 53.3% of GBC 55.4% of IHC, and 92.5% of EHC. Adjuvant chemotherapy or radiation was not associated with a survival benefit in R0 and/or N0 for all disease sites with the exception of radiation for R0 resections for EHC (34 months vs 31 months; p¼0.008). For R1 resections both chemotherapy
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http://dx.doi.org/10.1016/j.jamcollsurg.2017.07.848 ISSN 1072-7515/17
Vol. 225, No. 4S2, October 2017
and radiation were associated with a survival benefit for GBC (chemotherapy: 14.6 months vs 11.5 months; p¼0.05, radiation: 16.8 months vs 11.3 months; p<0.001) and EHC (chemotherapy: 22.4 months vs 15.3 months; p<0.001, radiation: 23 months vs 16.7 months; p<0.001). Nodal positive disease benefited from chemotherapy for all disease sites (GBC: 23.6 months vs 16.8 months; p<0.001, IHC 23 vs 17.2 months; p¼0.004, EHC: 24.3 vs 18.2 months; p<0.001) whereas radiation was associated with a survival benefit for GBC (25 months vs 18 months; p<0.001) and EHC (24.3 months vs 20 months; p<0.001). CONCLUSIONS: Surgical margins and the presence of nodal disease are the main determinants of survival outcomes after resection of localized biliary tract cancer. Adjuvant chemotherapy and radiation should be strongly considered in node positive patients as they derive the greatest benefit. Contemporary Analysis of Complications Associated with Biliary Stents During Neoadjuvant Therapy for Pancreatic Adenocarcinoma Bradford J Kim, MD, Laura R Prakash, Nisha Narula, MD, Catherine H Davis, MD, Thomas A Aloia, MD, FACS, Jean Nicolas Vauthey, MD, Jeffrey E Lee, MD, FACS, Jason B Fleming, MD, FACS, Matthew H Katz, MD, FACS, Ching-Wei D Tzeng, MD, FACS University of Texas MD Anderson Cancer Center, Houston, TX INTRODUCTION: Concern regarding risk for pre- or post-pancreaticoduodenectomy (PD) infection in patients with biliary stents may affect willingness to administer neoadjuvant therapy (NT) to patients with resectable pancreatic head adenocarcinoma (PDAC). We sought to document the contemporary incidence of stent-related complications (SRC) during NT and analyze their impact on postoperative infection. METHODS: Consecutive patients from a single institution (2011 to 2015) with PDAC treated with biliary decompression, NT, and PD were analyzed. Clinical variables and incidence of both infectious and non-infectious SRC (“stent cholangitis” defined as requiring antibiotics with admission and/or exchange) were compared to composite postoperative infections (defined as surgical site infection [SSI], organ space infection [OSI], and/or cholangitis).
Scientific Poster Presentations: 2017 Clinical Congress
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intervention, there was no association with composite surgical infections. The concern for post-PD infectious sequelae from biliary stents should not preclude the consideration of neoadjuvant therapy for PDAC. Evaluation of Our Approach (Modified Blumgart Anastomosis) to Reducing the Incidence of Postoperative Pancreatic Fistula after a Pancreaticoduodenectomy in Cases with a Soft Pancreas Ken Hayashi, Shigetoshi Yamada, Hiroshi Kusanagi, MD, Nobuyasu Kano, MD, FACS Kameda Medical Center, Kamogawa, Japan INTRODUCTION: Postoperative pancreatic fistula (POPF) is the most critical complication after a pancreaticoduodenectomy (PD), especially in cases with a soft pancreas. The ideal technical pancreatic reconstruction after PD continues to be debated. The aim of the present study was to evaluate our approach (modified Blumgart anastomosis) to reducing the incidence of POPF after PD. METHODS: Between August 2011 and December 2016, 116 patients who underwent PD were enrolled. Pancreatic reconstruction was performed using the modified Kakita method between August 2011 and May 2015 (K-group: n ¼ 72) and the modified Blumgart method between June 2015 and December 2016 (B-group: n ¼ 31). We then compared the clinical data for the 2 groups retrospectively. RESULTS: The median age was 70 (26-86) years (73 men and 43 women). Seventy-seven cases had a soft pancreas, while 39 cases had a hard pancreas. The incidence of POPF (Grade B, C) as defined according to the ISGPF was 25.0% overall, 30.6% for the K-group, and 15.9% for the B-group, with no significance difference observed between the 2 groups (p ¼ 0.077). Among the cases with soft pancreas, the incidence of POPF (Grade B, C) was 33.8% overall, 45.7% in the K-group, and 19.4% in the B-group, with a significant difference observed between the 2 groups (p ¼ 0028). CONCLUSIONS: The modified Blumgart method is useful for reducing the incidence of POPF, especially in cases with a soft pancreas.
RESULTS: Among 114 patients (median duration NT: 74 days; median time from first stent to surgery: 163 days), 110 (96%) had initial endoscopic (vs percutaneous) stents. Initial stents were plastic in 80 (70%), of which 47 (41%) were exchanged to metal before NT. Fifteen (13%) patients had stent cholangitis. SRC resulted in 66 preoperative stent replacements in 32 (28%) patients. Post-PD rates of SSI, OSI, and cholangitis were 23%, 5%, and 4%, respectively [composite rate 30%]. Grade 3 complication rate was 18%. After adjusting for pre-/intraoperative variables, SRC was not associated with composite surgical infections (p¼0.576).
Exploring Epithelial-Mesenchymal Transition: Suppressive miRNAs Using Combination of Cell-Based Reporter System and miRNA Library Hidekazu Hiramoto, Tomoki Muramatsu, Daisuke Ichikawa, MD, Kousuke Tanimoto, PhD, Syuhei Komatsu, Satoru Yasukawa, Eigo Otsuji, Johji Inazawa Kyoto Prefectural University of Medicine, Kyoto, Japan; Tokyo Medical and Dental University, Tokyo, Japan
CONCLUSIONS: Although SRC occurred in almost one-third of PDAC patients stented before and during NT, with appropriate
INTRODUCTION: The epithelial-mesenchymal transition (EMT) is known to contribute to malignant phenotypes including
Depleted Tumor Suppressor miR-107 in Plasma Relates to Tumor Progression and Is a Novel Therapeutic Target in Pancreatic Cancer Taisuke Imamura, MD, Shuhei Komatsu, MD, PhD, FACS, Daisuke Ichikawa, MD, Wataru Okajima, MD, PhD, Takuma Ohashi, Jun Kiuchi, MD, Keiji Nishibeppu, Hisashi Ikoma, Hiroki Taniguchi, MD, PhD, Eigo Otsuji Kyoto Prefectural University of Medicne, Kyoto Second Red Cross Hospital, Kyoto, Japan INTRODUCTION: This study explored decreased tumor suppressor microRNA (miRNA) plasma levels in pancreatic cancer (PCa) patients to clarify their potential as novel biomarkers and therapeutic targets. METHODS: We used the TorayÒ 3D-Gene microRNA arraybased approach to select candidates by comparing plasma levels between PCa patients and healthy volunteers. RESULTS: Six down-regulated miRNAs (miR-107, miR-126, miR-451, miR-145, miR-491-5p, and miR-146b-5p) were selected. Small- and large-scale analyses using samples from 100 PCa patients and 80 healthy volunteers revealed that miR-107 was the most down-regulated miRNA in PCa patients compared with healthy volunteers (p< 0.0001; area under the receiver-operating characteristic curve, 0.851). A low miR-107 plasma level was significantly associated with advanced T stage, N stage, and liver metastasis and was an independent factor predicting poor prognosis in PCa patients (p ¼ 0.012; hazard ratio, 4.56; 95% CI: 1.3817.4). miR-107 overexpression in PCa cells induced G1/S arrest with the production of p21 (targeting Notch2) and inhibited cell proliferation. In vivo, the restoration and maintenance of the miR-107 plasma level significantly inhibited tumor progression in mice. CONCLUSIONS: Depletion of the tumor suppressor miRNA-107 in plasma relates to tumor progression and poor outcomes. The restoration of the plasma miR-107 level might be a novel anticancer treatment strategy for PCa. Assessment of Patient Health literacy: A International Survey of Hepato-PancreatoBiliary (HPB) Surgeons Manuel Castillo-Angeles, MD, MPH, Rodrigo Calvillo-Ortiz, MD, Ammara A Watkins, MD, MPH, Danilo Acosta, MD, Carlos Chan, MD, Charles M Vollmer, Jr, MD, Tara S Kent, MD, FACS Beth Israel Deaconess Medical Center, Boston, MA
RESULTS: There were 149 survey participants (10.03 % response rate). A total of 87.2% were male and 66.7% were US surgeons. Patient literacy was most frequently assessed by general impression (89.2%) and by asking patients about employment (60.4%); 9.3% did not assess literacy. Forty-one percent of surgeons reported spending 30 minutes or less counseling new patients, and 13.4% reported spending more than 45 minutes. Pictures/diagrams (94.6%) and lay terminology (92.6%) were the most common patient education techniques, whereas only 6.7% used teach-back methods. Level of education and reading level were perceived by HPB surgeons to be greater than population-based data. US surgeons spent more time counseling patients when compared with non-US-based surgeons (p¼0.03). CONCLUSIONS: Even though HPB surgeons devote significant time to patient counseling, validated techniques to identify low literacy patients are infrequently used. Increased use of such techniques may contribute to improved patient participation, compliance, satisfaction, and overall health outcomes, and warrants further study. Biliary Tract Cancer Patient Selection for Adjuvant Chemotherapy and Radiation: A National Cancer Database Analysis Ioannis T Konstantinidis, MD, Zeljka Jutric, Philip HG Ituarte, PhD, Susanne G Warner, Laleh G Melstrom, MD, FACS, Gagandeep Singh, MD, Yuman Fong, MD, FACS City of Hope National Medical Center, Duarte, CA INTRODUCTION: Chemotherapy is associated with prolongation of survival for advanced biliary cancer. The role of adjuvant chemotherapy and radiation after resection with curative intent is not well established. METHODS: Data from 12,711 patients with biliary tract adenocarcinoma from the National Cancer Database (gallbladder (GBC): 6713, intrahepatic cholangiocarcinoma (IHC): 1923, extrahepatic cholangiocarcinoma (EHC): 4075) who underwent resection with microscopically negative (R0) or positive (R1) margins between 2004 and 2013 and had at least 3 months of followup were analyzed. Pathologic M1 cases were excluded.
INTRODUCTION: The ability to access, process and comprehend information about health care, known as functional health literacy, has been shown to improve outcomes. Our aim was to evaluate surgeons’ recognition of the role of health literacy in patient decision-making and understanding, and what techniques surgeons use to assess and accommodate patients’ needs.
RESULTS: The majority of resections were R0 for all disease sites (GBC: 84.3%, IHC: 83.7%, EHC: 80.4%). Lymph nodes were evaluated in 53.3% of GBC 55.4% of IHC, and 92.5% of EHC. Adjuvant chemotherapy or radiation was not associated with a survival benefit in R0 and/or N0 for all disease sites with the exception of radiation for R0 resections for EHC (34 months vs 31 months; p¼0.008). For R1 resections both chemotherapy
e120
http://dx.doi.org/10.1016/j.jamcollsurg.2017.07.848 ISSN 1072-7515/17
Vol. 225, No. 4S2, October 2017
and radiation were associated with a survival benefit for GBC (chemotherapy: 14.6 months vs 11.5 months; p¼0.05, radiation: 16.8 months vs 11.3 months; p<0.001) and EHC (chemotherapy: 22.4 months vs 15.3 months; p<0.001, radiation: 23 months vs 16.7 months; p<0.001). Nodal positive disease benefited from chemotherapy for all disease sites (GBC: 23.6 months vs 16.8 months; p<0.001, IHC 23 vs 17.2 months; p¼0.004, EHC: 24.3 vs 18.2 months; p<0.001) whereas radiation was associated with a survival benefit for GBC (25 months vs 18 months; p<0.001) and EHC (24.3 months vs 20 months; p<0.001). CONCLUSIONS: Surgical margins and the presence of nodal disease are the main determinants of survival outcomes after resection of localized biliary tract cancer. Adjuvant chemotherapy and radiation should be strongly considered in node positive patients as they derive the greatest benefit. Contemporary Analysis of Complications Associated with Biliary Stents During Neoadjuvant Therapy for Pancreatic Adenocarcinoma Bradford J Kim, MD, Laura R Prakash, Nisha Narula, MD, Catherine H Davis, MD, Thomas A Aloia, MD, FACS, Jean Nicolas Vauthey, MD, Jeffrey E Lee, MD, FACS, Jason B Fleming, MD, FACS, Matthew H Katz, MD, FACS, Ching-Wei D Tzeng, MD, FACS University of Texas MD Anderson Cancer Center, Houston, TX INTRODUCTION: Concern regarding risk for pre- or post-pancreaticoduodenectomy (PD) infection in patients with biliary stents may affect willingness to administer neoadjuvant therapy (NT) to patients with resectable pancreatic head adenocarcinoma (PDAC). We sought to document the contemporary incidence of stent-related complications (SRC) during NT and analyze their impact on postoperative infection. METHODS: Consecutive patients from a single institution (2011 to 2015) with PDAC treated with biliary decompression, NT, and PD were analyzed. Clinical variables and incidence of both infectious and non-infectious SRC (“stent cholangitis” defined as requiring antibiotics with admission and/or exchange) were compared to composite postoperative infections (defined as surgical site infection [SSI], organ space infection [OSI], and/or cholangitis).
Scientific Poster Presentations: 2017 Clinical Congress
e121
intervention, there was no association with composite surgical infections. The concern for post-PD infectious sequelae from biliary stents should not preclude the consideration of neoadjuvant therapy for PDAC. Evaluation of Our Approach (Modified Blumgart Anastomosis) to Reducing the Incidence of Postoperative Pancreatic Fistula after a Pancreaticoduodenectomy in Cases with a Soft Pancreas Ken Hayashi, Shigetoshi Yamada, Hiroshi Kusanagi, MD, Nobuyasu Kano, MD, FACS Kameda Medical Center, Kamogawa, Japan INTRODUCTION: Postoperative pancreatic fistula (POPF) is the most critical complication after a pancreaticoduodenectomy (PD), especially in cases with a soft pancreas. The ideal technical pancreatic reconstruction after PD continues to be debated. The aim of the present study was to evaluate our approach (modified Blumgart anastomosis) to reducing the incidence of POPF after PD. METHODS: Between August 2011 and December 2016, 116 patients who underwent PD were enrolled. Pancreatic reconstruction was performed using the modified Kakita method between August 2011 and May 2015 (K-group: n ¼ 72) and the modified Blumgart method between June 2015 and December 2016 (B-group: n ¼ 31). We then compared the clinical data for the 2 groups retrospectively. RESULTS: The median age was 70 (26-86) years (73 men and 43 women). Seventy-seven cases had a soft pancreas, while 39 cases had a hard pancreas. The incidence of POPF (Grade B, C) as defined according to the ISGPF was 25.0% overall, 30.6% for the K-group, and 15.9% for the B-group, with no significance difference observed between the 2 groups (p ¼ 0.077). Among the cases with soft pancreas, the incidence of POPF (Grade B, C) was 33.8% overall, 45.7% in the K-group, and 19.4% in the B-group, with a significant difference observed between the 2 groups (p ¼ 0028). CONCLUSIONS: The modified Blumgart method is useful for reducing the incidence of POPF, especially in cases with a soft pancreas.
RESULTS: Among 114 patients (median duration NT: 74 days; median time from first stent to surgery: 163 days), 110 (96%) had initial endoscopic (vs percutaneous) stents. Initial stents were plastic in 80 (70%), of which 47 (41%) were exchanged to metal before NT. Fifteen (13%) patients had stent cholangitis. SRC resulted in 66 preoperative stent replacements in 32 (28%) patients. Post-PD rates of SSI, OSI, and cholangitis were 23%, 5%, and 4%, respectively [composite rate 30%]. Grade 3 complication rate was 18%. After adjusting for pre-/intraoperative variables, SRC was not associated with composite surgical infections (p¼0.576).
Exploring Epithelial-Mesenchymal Transition: Suppressive miRNAs Using Combination of Cell-Based Reporter System and miRNA Library Hidekazu Hiramoto, Tomoki Muramatsu, Daisuke Ichikawa, MD, Kousuke Tanimoto, PhD, Syuhei Komatsu, Satoru Yasukawa, Eigo Otsuji, Johji Inazawa Kyoto Prefectural University of Medicine, Kyoto, Japan; Tokyo Medical and Dental University, Tokyo, Japan
CONCLUSIONS: Although SRC occurred in almost one-third of PDAC patients stented before and during NT, with appropriate
INTRODUCTION: The epithelial-mesenchymal transition (EMT) is known to contribute to malignant phenotypes including