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Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer
Poster Session, Sunday 29 January 2017 Conclusion: This is the first study to our knowledge that explored mtDNA deletions and folate status in Egyptian patients with HCV related HCC and is the first to evaluate mtDNA deletions as diagnostic markers for HCC at a cutoff value of 2.65 (DCt) with a sensitivity of 82% and a specificity of 60%. Our findings implied a causal relationship between folate deficiency and mtDNA deletions frequency among Egyptian patients with HCV related HCC. Moreover, mtDNA deletions correlated with the clinic-pathological features and poor survival in HCC patients. No conflict of interest. 607 POSTER Naringin: a novel anticancer candidate against chemically induced hepatocellular carcinoma in rats V. Kumar1 , A. Verma1 . 1 Sam Higginbotham Institute of AgricultureTechnology & Sciences, Pharmaceutical Sciences, Faculty of Health Sciences, India Background: Naringin has been projected as a promising agent for cancer chemotherapeutics. The aim of the current study was to scrutinize the chemoprotective action and possible mechanisms Naringin against Diethylnitrosamine (DEN)-induced hepatocellular carcinoma in rats. Material and Methods: In-vitro experimental study was carried out on the cell lines such as HuH-7 and HepG2 cells. Swiss Albino Wistar rats were used in the current study. Different doses of Naringin (20, 50 and 100 mg/kg/day) was orally administered to DEN induced HCC rats for 22 weeks. We also macroscopically estimated the incidence of hepatic dyschromatic nodules. We determined the biochemical, antioxidant and haematological parameters. Histopathology and Immunohistochemical study were also performed. Cyclooxygenase 2, Ki-67, nuclear factor kappa B (NF-úB) and inducible nitric oxide were estimated in all group rats via immunohistochemical staining of hepatic tissue. Result and Discussion: Cell lines study showed that the Naringin enhanced the DNA damage, caspase-3 and cell arrest and reduced the nuclear factor-Kappa B activation. DEN control group rats showed the increase number and incidence of hepatic dyschromatic nodules, which was significantly reduced by the Naringin at dose dependently. Naringin also altered the biochemical and haematological parameter at dose dependently. Moreover, Naringin altered the antioxidant parameter including catalase (CAT), superoxide dismutase (SOD), glutathione-Stransferase (GST) and reduced the protein carbonyl, malondialdehyde and myeloperoxidase in the liver. Naringin Naringin also reduced the area and number of placental glutathione S-tranasferase-positive foci in the hepatic tissue of DEN induced control rats. DEN induced rats showed the increased activity of Cyclooxygenase 2, Ki-67, nuclear factor kappa B (NF-úB) and inducible nitric oxide, which was inhibited by the Naringin. DEN control rats demonstrated the depletion of M30 cyto-Death and number of cells positive for TUNNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling), which was blocked by the Naringin. Conclusion: It can be concluded on the basic of the result that the Naringin confirmed the chemoprotective effect against the DEN induced HCC rats via induction of apoptosis and reduction of cell proliferation or we can say that the Naringin also protected liver from the oxidative damage and inflammatory reaction. No conflict of interest. 607A POSTER Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer
Abstracts
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June 2010, 190 patients in the gemcitabine group and 187 in the S-1 group constituted the full analysis set. The interim analysis on July 2012 showed that the hazard ratio for death of S-1 was 0.55 (99.8% CI, 0.36– 0.84, p < 0.0001). Analysis with the follow-up data on January 2016 showed that median survival times and 5-year survival rates were 25.5 months and 24.4% in the gemcitabine group and 46.5 months and 44.1% in the S-1 group (hazard ratio; 0.57, 95% CI, 0.44–0.72, p < 0.0001), respectively. Grade 3 or 4 adverse events including infection, leukopenia, neutropenia, thrombocytopenia, aspartate aminotransferase, alanine aminotransferase were observed more frequently in the gemcitabine group, while stomatitis and diarrhea were more frequently experienced in the S-1 group. Conclusions: JASPAC 01 study clearly showed superiority of S-1 to gemcitabine as adjuvant chemotherapy for resected pancreatic cancer. The Pancreatic Cancer Medical Guideline of Japan recommends usage of S-1 as the first choice for postoperative adjuvant chemotherapy. No conflict of interest. 608 POSTER Clinical significance of D2-40 and CD31, lymphatic and blood vessel invasion markers, in gastric cancer A. Ihvan1 , A. Acar2 , C. Topal2 , T. Canbak2 , S. Aktas2 , E. Unal2 . 1 Health Sciences University Umraniye Training and Research Hospital, Department of Pathology, Istanbul, Turkey; 2 Health Sciences University Umraniye Training and Research Hospital, Department of General Surgery, Istanbul, Turkey Background: Lymphatic and/or blood vessel tumor invasion (LBVI) is the critical step in establishing tumor cell dissemination and metastasis in various types of cancers including gastric carcinoma (GC). Recently, the immunohistochemical detection of LBVI has been shown to have a higher sensitivity and specificity than classic staining methods. Material and Methods: Patients with GC who underwent curative gastrectomy with standard D2 lymph node dissection in our clinic between January 2008 and July 2011 included in the study. Demographics, involvement of the lymph nodes, lymphatic and vascular invasion and overall survival were determined. Lymhovascular involvement was evaluated by using H&E as routine staining, and CD31/D2-40 as immunohistochemical markers. Results: Fifty-two patients (32 male, 20 female) were present. Mean age was 58 (range 29−72). H&E-LBVI was determined as positive in 29 (55.8%) cases. CD31-BVI and D2-40-LVI were positive in 29 (55.8%) and 34 (65.4%) cases, respectively. There was no statistical difference between these methods using the Mc Nemar test (p > 0.05). CD31+D2-40 was positive in 39 (75%) patients, and there was a statistically significant difference between CD31±D2-40 and H&E methods (p < 001). All of the H&E, CD31, D2-40 and CD31+D2-40 markers were significantly associated with lymph node metastasis (p < 001, each). D2-40 and CD31±D2-40 markers were significantly associated with distant metastasis (p < 005, each). Five-year survival rate was significantly lower in lymp-node positive patients (p < 001). Conclusions: In detection of vascular invasion, each of the immunomarkers CD31 and D2-40 have shown to be unsuccessful in taking better results. However, when these two immunomarkers are used together, the results are significantly paramount in showing the involvement of LBVI. In our opinion, CD31 and D2-40 should be used together while evaluating gastric resection specimens. No conflict of interest. 608A POSTER Metformin reduces esophageal cancer risk in Taiwanese patients with type 2 diabetes
N. Boku1 , K. Uesaka2 . 1 Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Japan; 2 Division of Hepato-BiliaryPancreatic Surgery, Shizuoka Cancer Center Hospital, Japan
C.H. Tseng1 . 1 National Taiwan University College of Medicine, Department of Internal Medicine, Taipei, Taiwan
Background: There have been some important studies on postoperative adjuvant chemotherapy for pancreatic cancer, including CONKO-001, JASPAC 01, and ESPAC-4, during the past decade. Study design of JASPAC 01: JASPAC 01 study is a multi-center (33 institutions in Japan), open-label, randomized phase 3 trial aiming at assessing non-inferiority of S-1 to gemcitabine as adjuvant chemotherapy for resected pancreatic cancer in terms of overall survival. Patients with resected pancreatic cancer were randomly assigned to the gemcitabine group (gemcitabine of 1000 mg/m2 , intravenously administered on days 1, 8, and 15, every 4 weeks up to 6 cycles) or the S-1 group (S-1 of 40, 50, or 60 mg according to body-surface area, orally administered twice daily for 28 days, every 6 weeks up to 4 cycles) at the data center with a modified minimization method, balancing residual tumor status, nodal status and institutions. The expected hazard ratio was 0.87 with a noninferiority margin of 1.25 (power 80% and one-sided type one error 2.5%). Results: Excluding 3 ineligible patients and 5 who did not receive chemotherapy from 385 patients enrolled between April 2007 and
Background: This study evaluated whether metformin might reduce esophageal cancer risk. Materials and Methods: Patients with type 2 diabetes diagnosed during 1999–2005 were recruited from the reimbursement database of Taiwan’s National Health Insurance. A total of 16,216 ever users and 16,216 never users of metformin (matched on propensity scores) were followed until December 31, 2011. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score. Results: The incidence of esophageal cancer in ever and never users was 28.49 and 50.87 per 100,000 person-years, respectively. The overall hazard ratio (95% confidence intervals) of 0.557 (0.329–0.944) suggested a significantly lower risk among metformin users. Hazard ratios comparing the first (<21.47 months), second (21.47–45.93 months) and third (>45.93 months) tertile of cumulative duration of metformin use to never users was 1.490 (0.816–2.720), 0.439 (0.185–1.040) and 0.063 (0.009–0.460), respectively.
Abstracts
S77
June 2010, 190 patients in the gemcitabine group and 187 in the S-1 group constituted the full analysis set. The interim analysis on July 2012 showed that the hazard ratio for death of S-1 was 0.55 (99.8% CI, 0.36– 0.84, p < 0.0001). Analysis with the follow-up data on January 2016 showed that median survival times and 5-year survival rates were 25.5 months and 24.4% in the gemcitabine group and 46.5 months and 44.1% in the S-1 group (hazard ratio; 0.57, 95% CI, 0.44–0.72, p < 0.0001), respectively. Grade 3 or 4 adverse events including infection, leukopenia, neutropenia, thrombocytopenia, aspartate aminotransferase, alanine aminotransferase were observed more frequently in the gemcitabine group, while stomatitis and diarrhea were more frequently experienced in the S-1 group. Conclusions: JASPAC 01 study clearly showed superiority of S-1 to gemcitabine as adjuvant chemotherapy for resected pancreatic cancer. The Pancreatic Cancer Medical Guideline of Japan recommends usage of S-1 as the first choice for postoperative adjuvant chemotherapy. No conflict of interest. 608 POSTER Clinical significance of D2-40 and CD31, lymphatic and blood vessel invasion markers, in gastric cancer A. Ihvan1 , A. Acar2 , C. Topal2 , T. Canbak2 , S. Aktas2 , E. Unal2 . 1 Health Sciences University Umraniye Training and Research Hospital, Department of Pathology, Istanbul, Turkey; 2 Health Sciences University Umraniye Training and Research Hospital, Department of General Surgery, Istanbul, Turkey Background: Lymphatic and/or blood vessel tumor invasion (LBVI) is the critical step in establishing tumor cell dissemination and metastasis in various types of cancers including gastric carcinoma (GC). Recently, the immunohistochemical detection of LBVI has been shown to have a higher sensitivity and specificity than classic staining methods. Material and Methods: Patients with GC who underwent curative gastrectomy with standard D2 lymph node dissection in our clinic between January 2008 and July 2011 included in the study. Demographics, involvement of the lymph nodes, lymphatic and vascular invasion and overall survival were determined. Lymhovascular involvement was evaluated by using H&E as routine staining, and CD31/D2-40 as immunohistochemical markers. Results: Fifty-two patients (32 male, 20 female) were present. Mean age was 58 (range 29−72). H&E-LBVI was determined as positive in 29 (55.8%) cases. CD31-BVI and D2-40-LVI were positive in 29 (55.8%) and 34 (65.4%) cases, respectively. There was no statistical difference between these methods using the Mc Nemar test (p > 0.05). CD31+D2-40 was positive in 39 (75%) patients, and there was a statistically significant difference between CD31±D2-40 and H&E methods (p < 001). All of the H&E, CD31, D2-40 and CD31+D2-40 markers were significantly associated with lymph node metastasis (p < 001, each). D2-40 and CD31±D2-40 markers were significantly associated with distant metastasis (p < 005, each). Five-year survival rate was significantly lower in lymp-node positive patients (p < 001). Conclusions: In detection of vascular invasion, each of the immunomarkers CD31 and D2-40 have shown to be unsuccessful in taking better results. However, when these two immunomarkers are used together, the results are significantly paramount in showing the involvement of LBVI. In our opinion, CD31 and D2-40 should be used together while evaluating gastric resection specimens. No conflict of interest. 608A POSTER Metformin reduces esophageal cancer risk in Taiwanese patients with type 2 diabetes
N. Boku1 , K. Uesaka2 . 1 Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Japan; 2 Division of Hepato-BiliaryPancreatic Surgery, Shizuoka Cancer Center Hospital, Japan
C.H. Tseng1 . 1 National Taiwan University College of Medicine, Department of Internal Medicine, Taipei, Taiwan
Background: There have been some important studies on postoperative adjuvant chemotherapy for pancreatic cancer, including CONKO-001, JASPAC 01, and ESPAC-4, during the past decade. Study design of JASPAC 01: JASPAC 01 study is a multi-center (33 institutions in Japan), open-label, randomized phase 3 trial aiming at assessing non-inferiority of S-1 to gemcitabine as adjuvant chemotherapy for resected pancreatic cancer in terms of overall survival. Patients with resected pancreatic cancer were randomly assigned to the gemcitabine group (gemcitabine of 1000 mg/m2 , intravenously administered on days 1, 8, and 15, every 4 weeks up to 6 cycles) or the S-1 group (S-1 of 40, 50, or 60 mg according to body-surface area, orally administered twice daily for 28 days, every 6 weeks up to 4 cycles) at the data center with a modified minimization method, balancing residual tumor status, nodal status and institutions. The expected hazard ratio was 0.87 with a noninferiority margin of 1.25 (power 80% and one-sided type one error 2.5%). Results: Excluding 3 ineligible patients and 5 who did not receive chemotherapy from 385 patients enrolled between April 2007 and
Background: This study evaluated whether metformin might reduce esophageal cancer risk. Materials and Methods: Patients with type 2 diabetes diagnosed during 1999–2005 were recruited from the reimbursement database of Taiwan’s National Health Insurance. A total of 16,216 ever users and 16,216 never users of metformin (matched on propensity scores) were followed until December 31, 2011. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score. Results: The incidence of esophageal cancer in ever and never users was 28.49 and 50.87 per 100,000 person-years, respectively. The overall hazard ratio (95% confidence intervals) of 0.557 (0.329–0.944) suggested a significantly lower risk among metformin users. Hazard ratios comparing the first (<21.47 months), second (21.47–45.93 months) and third (>45.93 months) tertile of cumulative duration of metformin use to never users was 1.490 (0.816–2.720), 0.439 (0.185–1.040) and 0.063 (0.009–0.460), respectively.