- Email: [email protected]
PP071 THERAPEUTIC EFFECTS OF KUROZU-MOROMIMATSU AND KUROZU ON DIETHYLNITROSAMINE-INDUCED HEPATOCELLULAR CARCINOMA ANIMAL MODEL
50 PP069 Outstanding abstract AN ENHANCED RECOVERY AFTER SURGERY PROGRAM IN PATIENTS WHO HAVE UNDERGONE AFTER THORACIC ESOPHAGEAL CANCER SURGERY H. Sato1 , M. Niihara1 , Y. Tsubosa1 . 1 Esophageal Surgery, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan Rationale: Data on enhanced recovery after surgery (ERAS) of thoracic esophageal cancer are sparse. The aim of this study was to evaluate the impact of an ERAS program in patients who had undergone transthoracic esophagectomy (TE). Methods: 59 patients who underwent a TE were put enrolled into the ERAS program which included early postoperative enteral nutrition (EN) and mobilisation (Group A). The program was started on the first postoperative day (1POD). This group was then compared with a group of 42 patients who had received the traditional postoperative regimen, including total parental nutrition without EN (Group B). Mobilization was initiated on 2POD and EN was begun on 6POD in Group B patients. Routine broncoscopy for toiletting sputum and mechanical bowel preparation (MBP) were performed in all patients in Group B, but only when considered to be necessary in Group A. The outcome measures comprised the morbidity rate, pneumonia, body weight loss, and length of hospital stay. This was a retrospective cohort study using historical controls. Differences between groups were examined for statistical significance using the chi-square, Fisher’s exact test or the Mann-Whitney U-test. Results: The rate of morbidity, pneumonia were 44% and, 7%, as well as 60% and 10% in Groups A and B, respectively (P = 0.13, 0.61). The average post-operative days when the patients started walking in Groups A and B were 1.0 and 2.8 days, respectively. The length of hospital stay was reduced in Group A in comparison to that in Group B (median 20.8 versus 24 days; P =0.047). On the day of discharge or at 21POD, the rates of body weight loss were 3.7% and 5.7% (P = 0.004) in Groups A and B, respectively. Conclusion: The ERAS program after TE was therefore found to improve post-operative body weight loss and reduce the length of hospital stay. Routine broncoscopy and MBP were found to not be necessary in such patients. Disclosure of Interest: None declared
PP070 NUTRITIONAL SCREENING TOOL IN HEAD AND NECK CANCER PATIENTS L. Arribas1 , E. Vilajosana2 , E. Fort1 , L. Hurt´ os1 , I. Peir´ o1 . 1 2 Unitat Funcional de Nutricio Clinica, Enfermera Clínica de la Unidad Funcional de Cabeza y Cuello, Institut Catala d’Oncologia l’Hospitalet, Barcelona, Spain Rationale: Head and neck cancer patients are especially at risk of malnutrition. Estimated data report between 30 75% of malnutrition depending when if the screening is done at the diagnosis or during treatment. The purpose of our study is to create and validate an easy and quicker screening tool for head and neck cancer patients before starting treatment.
Poster presentations Methods: This is a prospective study. All consecutive patients diagnosed with head and neck cancer attending to the head and neck cancer multidisciplinary committee between May and October 2010 were assessed with the patient generated subjective global assessment (PGSGA) and a new nutritional screening tool that we have created according to weight loss, nutritional intake, tumor location and treatment. This is a continuous measure, easy and quicker than PG-SGA to be done by any health professional no familiarize with nutrition. A score 6 indicates a need for nutritional intervention. Results: We have included 38 patients. Both nutritional screening tools show 26.3% of malnutrition. Comparing our screening with PG-SGA we obtained a sensibility of 90% and specificity of 96%. The median weight loss in malnourished patients is 9.15% with SD±4.54. There is no significant weight loss in well nourished patients. The location with greatest weight loss is oropharyngeal and hypopharyngeal cancer as well as the bigger tumors (T4 and T3). Conclusion: According to the results obtained until today, the new nutritional screening seems an easy, useful and quick tool for this group of patients. The sample of the study is small so we are hoping to improve our results in the future. Due to the simplicity of the method, the tool could be filled by any health professional without nutritional background. References Bauer J. Use of the scored Patient-Generated Subjective Global Assessment (PG-SGA) as a nutrition assessment tool in patients with cancer. Eur. J. Clin. Nutr; 2002; 56; 779 785. Disclosure of Interest: None declared
PP071 THERAPEUTIC EFFECTS OF KUROZU-MOROMIMATSU AND KUROZU ON DIETHYLNITROSAMINE-INDUCED HEPATOCELLULAR CARCINOMA ANIMAL MODEL T. Shizuma1 , K. Ishiwata1 , H. Mori1 , M. Nagano2 , N. Fukuyama1 . 1 Department of physiology, school of medicine, Tokai University, Isehara, 2 Sakamoto Brewing Co., Ltd., Kagoshima, Japan Rationale: We examined the therapeutic effects of Kurozu (a traditional Japanese unpolished vinegar) and Kurozu Moromimatsu (Kurozu-M) in an animal model of diethylnitrosamine (DEN)-induced HCC. Methods: F344 rats(n = 30) were divided into the 3 groups; the control group received basal CE-2 diet, the Kurozu group received CE-2 diet containing 3.2% solution of Kurozu, and the Kurozu-M group received CE-2 diet containing 2% Kurozu-M. Administration of DEN (200 mg/kg/week) was performed 3 times by intraperitoneal injection to prepare the DEN-induced HCC animal model.At 16 weeks after first administration of DEN, levels of serum transaminases in half the rats (each group; n = 5)were measured. The same rats were then sacrificed and their livers were resected. Microscopic examination of liver tissues was carried our by H.E. staining and occurrence of HCC was evaluated by glutathione S-transferase placental form (GST-P) staining (markers of HCC and precancerous lesions, respectively).The other
Nutrition and cancer I
51
rats of each group (n = 5) were maintained on the same diets and their survival was evaluated. Statistical analysis of differences in serum transaminase levels in sacrificed rats was performed by one-way ANOVA. Differences in survival rates of the non-sacrificed rats were analyzed by the Kaplan-Meier method. Results: There were no significant differences of levels of transaminases among the three groups. There were also no marked histological differences in liver injury among the three groups. However, GST-P staining was remarkably reduced in the Kurozu-M group, followed by the Kurozu group. Survival was significantly increased in the Kurozu-M and Kurozu groups in comparison with the control group. Conclusion: Kurozu-M and Kurozu inhibited the development of HCC in the DEN-induced rodent model. Disclosure of Interest: None declared
PP072 EFFECT OF N-3 AND N-6 POLYUNSATURATED FATTY ACIDS DURING RADIOTHERAPY IN HUMAN COLORECTAL CANCER CELLS AND XENOGRAFTED NUDE MICE F. Cai1 , V. Granci1 , M. Rouzaud2 , R. Miralbell2 , Y.M. Dupertuis1 , C. Pichard1 . 1 Unit of Nutrition, 2 Radio-Oncology, Geneva University Hospital, Geneva, 14, Switzerland Rationale: N-3 and n-6 polyunsaturated fatty acids (PUFAs) have been described as having opposite effects on tumour growth. Therefore, we evaluated if they could modulate the effect of radiotherapy (RT) in vitro and in vivo in human colorectal adenocarcinoma xenografted nude mice. Methods: HT-29 cells were pre-treated with n-3 or n-6 PUFAs for 24 hours and then exposed to single X-ray doses. Short- and long-term effects were measured by MTT and clonogenic assays, respectively. Cell cycle was analysed by flow cytometry. HT-29 xenografted nude mice were treated with 11 daily IV injections of n-3 or n-6 PUFAs (Omegaven® or Lipovenos® , Fresenius Kabi) w/o fractionated-dose RT of 5 x 3.5 Gy. The tumour volume was measured every two days. Mice were then sacrificed and tumour and tissues were collected. Data are presented as means±SD (%) (n = 6/group). Results: In vitro, both n-3 and n-6 PUFAs could increase HT29 cell radiosensitivity in a time- and dose-dependant manner, through cell accumulation in S/G2 phases. However, these in vitro results could bot be confirmed in vivo, although tumour growth seemed to be slightly reduced by the combination of RT with n-3 PUFAs (see table). Table: Effect of n-6 or n-3 PUFAs alone or in combination with fractionated-dose radiotherapy (RT) Controls
n-6 PUFAs n-3 PUFAs RT
RT + RT + n-6 PUFAs n-3 PUFAs
Fold-change in tumour volume 6.0±1.4 5.6±1.0 6.0±1.2 2.8±0.8* 3.2±1.1* 2.6±0.6* Tumour weight (g) 0.9±0.4 0.9±0.3 0.8±0.3 0.9±0.5 0.8±0.3 0.6±0.2 Body weight change (g) +0.8±1.3 +0.5±2.7 +0.2±0.7 +0.9±1.7 +0.3±1.7 0.2±2.6
Conclusion: Our in vitro results confirmed that administration of n-3 PUFAs can inhibit colorectal cancer cell growth and enhance the cytotoxic effect of RT. However,
this inhibitory effect could not be reproduced in vivo in an animal model of xenografted colorectal tumour. Disclosure of Interest: F. Cai Grant/Research Support from: Foundation Nutrition 2000Plus, V. Granci Grant/Research Support from: Swiss National Science Foundation grant nº 310030 116738, M. Rouzaud: None declared, R. Miralbell: None declared, Y. Dupertuis Grant/Research Support from: Swiss National Science Foundation grant nº 310030 116738, C. Pichard Grant/Research Support from: Foundation Nutrition 2000Plus
PP073 MODULATORY EFFECTS OF POLYUNSATURATED FATTY ACIDS ON DIFFERENT CHEMOTHERAPEUTIC AGENTS V. Granci1 , F. Cai1 , Y.M. Dupertuis1 , C. Pichard1 . 1 Clinical Nutrition, University Hospital of Geneva, Geneva, Switzerland Rationale: Numerous evidences indicate an interest to combine chemotherapy with n-3 polyunsaturated fatty acids (n-3 PUFAs) in human cancers. We investigate the effects of fish oil (FO) (Omegaven® , Fresenius Kabi) and soybean oil (SO) (Lipoveneos® , Fresenius Kabi) emulsion enriched in n-3 PUFAs on conventional chemotherapeutical drugs such as irinotecan (CPT-11), Oxaliplatin and 5-Fluorouracil (5-FU). Methods: After treatment, viability of the human colorectal cancer cells HT-29 was evaluated using a MTT assay. Cell cycle and apoptosis was analyzed by flow cytometry with PI alone or combined with annexin-V, respectively. For analysis of caspase activation, Western blot analysis was applied. Results: A decrease in cell viability was observed when cells were treated with FO in combination with low doses of CPT-11, 5-FU or Oxaliplatin regardless of the incubation time. Table: HT-29 cell survival after a 48-h or 72-h chemotherapy w/o Fish oil or soybean oil emulsion as measured by MTT assay (*P < 0.05). Cell survival
48 h
Chemotherapy
Alone
+ FO
+ SO
Alone
73 h + FO
+ SO
5-FU CPT-11 Oxaliplatin
85.5±6.3 88.2±3 78.1±7.7
74.7±7.7 73.8±11* 59.1±4.9*
92.5±5.8 90.3±7.6 70.1±9.8
90±3.7 77.7±5.4 75.3±5.7
62.1±7.9* 64.7±4.6* 52.5±8.8*
84.7±12.7 70.2±9.1 66.8±9.1
Moreover, FO enhanced the pro-apoptotic effect of the three anti-cancer drugs compared with chemotherapy alone, as revealed by annexin V staining (P < 0.05). These observations were confirmed by analysis of caspase-3 expression showing the cleaved-caspase-3 product under FO and chemotherapy. Conclusion: These results indicate a specific synergy between n-3 PUFAs and anticancer agents commonly used in colorectal cancer chemotherapy. Further in vivo experiments are underway to highlight the mechanisms of action of such a combination for colorectal cancer chemotherapy. Disclosure of Interest: V. Granci Grant/Research Support from: Swiss National Science Foundation grant nº 310030 116738, F. CAI Grant/Research Support from: Foundation Nutrition 2000Plus, Y. Dupertuis Grant/Research Support from: Swiss National Science Foundation grant nº 310030 116738, C. Pichard Grant/Research Support from: Foundation Nutrition 2000Plus
PP070 NUTRITIONAL SCREENING TOOL IN HEAD AND NECK CANCER PATIENTS L. Arribas1 , E. Vilajosana2 , E. Fort1 , L. Hurt´ os1 , I. Peir´ o1 . 1 2 Unitat Funcional de Nutricio Clinica, Enfermera Clínica de la Unidad Funcional de Cabeza y Cuello, Institut Catala d’Oncologia l’Hospitalet, Barcelona, Spain Rationale: Head and neck cancer patients are especially at risk of malnutrition. Estimated data report between 30 75% of malnutrition depending when if the screening is done at the diagnosis or during treatment. The purpose of our study is to create and validate an easy and quicker screening tool for head and neck cancer patients before starting treatment.
Poster presentations Methods: This is a prospective study. All consecutive patients diagnosed with head and neck cancer attending to the head and neck cancer multidisciplinary committee between May and October 2010 were assessed with the patient generated subjective global assessment (PGSGA) and a new nutritional screening tool that we have created according to weight loss, nutritional intake, tumor location and treatment. This is a continuous measure, easy and quicker than PG-SGA to be done by any health professional no familiarize with nutrition. A score 6 indicates a need for nutritional intervention. Results: We have included 38 patients. Both nutritional screening tools show 26.3% of malnutrition. Comparing our screening with PG-SGA we obtained a sensibility of 90% and specificity of 96%. The median weight loss in malnourished patients is 9.15% with SD±4.54. There is no significant weight loss in well nourished patients. The location with greatest weight loss is oropharyngeal and hypopharyngeal cancer as well as the bigger tumors (T4 and T3). Conclusion: According to the results obtained until today, the new nutritional screening seems an easy, useful and quick tool for this group of patients. The sample of the study is small so we are hoping to improve our results in the future. Due to the simplicity of the method, the tool could be filled by any health professional without nutritional background. References Bauer J. Use of the scored Patient-Generated Subjective Global Assessment (PG-SGA) as a nutrition assessment tool in patients with cancer. Eur. J. Clin. Nutr; 2002; 56; 779 785. Disclosure of Interest: None declared
PP071 THERAPEUTIC EFFECTS OF KUROZU-MOROMIMATSU AND KUROZU ON DIETHYLNITROSAMINE-INDUCED HEPATOCELLULAR CARCINOMA ANIMAL MODEL T. Shizuma1 , K. Ishiwata1 , H. Mori1 , M. Nagano2 , N. Fukuyama1 . 1 Department of physiology, school of medicine, Tokai University, Isehara, 2 Sakamoto Brewing Co., Ltd., Kagoshima, Japan Rationale: We examined the therapeutic effects of Kurozu (a traditional Japanese unpolished vinegar) and Kurozu Moromimatsu (Kurozu-M) in an animal model of diethylnitrosamine (DEN)-induced HCC. Methods: F344 rats(n = 30) were divided into the 3 groups; the control group received basal CE-2 diet, the Kurozu group received CE-2 diet containing 3.2% solution of Kurozu, and the Kurozu-M group received CE-2 diet containing 2% Kurozu-M. Administration of DEN (200 mg/kg/week) was performed 3 times by intraperitoneal injection to prepare the DEN-induced HCC animal model.At 16 weeks after first administration of DEN, levels of serum transaminases in half the rats (each group; n = 5)were measured. The same rats were then sacrificed and their livers were resected. Microscopic examination of liver tissues was carried our by H.E. staining and occurrence of HCC was evaluated by glutathione S-transferase placental form (GST-P) staining (markers of HCC and precancerous lesions, respectively).The other
Nutrition and cancer I
51
rats of each group (n = 5) were maintained on the same diets and their survival was evaluated. Statistical analysis of differences in serum transaminase levels in sacrificed rats was performed by one-way ANOVA. Differences in survival rates of the non-sacrificed rats were analyzed by the Kaplan-Meier method. Results: There were no significant differences of levels of transaminases among the three groups. There were also no marked histological differences in liver injury among the three groups. However, GST-P staining was remarkably reduced in the Kurozu-M group, followed by the Kurozu group. Survival was significantly increased in the Kurozu-M and Kurozu groups in comparison with the control group. Conclusion: Kurozu-M and Kurozu inhibited the development of HCC in the DEN-induced rodent model. Disclosure of Interest: None declared
PP072 EFFECT OF N-3 AND N-6 POLYUNSATURATED FATTY ACIDS DURING RADIOTHERAPY IN HUMAN COLORECTAL CANCER CELLS AND XENOGRAFTED NUDE MICE F. Cai1 , V. Granci1 , M. Rouzaud2 , R. Miralbell2 , Y.M. Dupertuis1 , C. Pichard1 . 1 Unit of Nutrition, 2 Radio-Oncology, Geneva University Hospital, Geneva, 14, Switzerland Rationale: N-3 and n-6 polyunsaturated fatty acids (PUFAs) have been described as having opposite effects on tumour growth. Therefore, we evaluated if they could modulate the effect of radiotherapy (RT) in vitro and in vivo in human colorectal adenocarcinoma xenografted nude mice. Methods: HT-29 cells were pre-treated with n-3 or n-6 PUFAs for 24 hours and then exposed to single X-ray doses. Short- and long-term effects were measured by MTT and clonogenic assays, respectively. Cell cycle was analysed by flow cytometry. HT-29 xenografted nude mice were treated with 11 daily IV injections of n-3 or n-6 PUFAs (Omegaven® or Lipovenos® , Fresenius Kabi) w/o fractionated-dose RT of 5 x 3.5 Gy. The tumour volume was measured every two days. Mice were then sacrificed and tumour and tissues were collected. Data are presented as means±SD (%) (n = 6/group). Results: In vitro, both n-3 and n-6 PUFAs could increase HT29 cell radiosensitivity in a time- and dose-dependant manner, through cell accumulation in S/G2 phases. However, these in vitro results could bot be confirmed in vivo, although tumour growth seemed to be slightly reduced by the combination of RT with n-3 PUFAs (see table). Table: Effect of n-6 or n-3 PUFAs alone or in combination with fractionated-dose radiotherapy (RT) Controls
n-6 PUFAs n-3 PUFAs RT
RT + RT + n-6 PUFAs n-3 PUFAs
Fold-change in tumour volume 6.0±1.4 5.6±1.0 6.0±1.2 2.8±0.8* 3.2±1.1* 2.6±0.6* Tumour weight (g) 0.9±0.4 0.9±0.3 0.8±0.3 0.9±0.5 0.8±0.3 0.6±0.2 Body weight change (g) +0.8±1.3 +0.5±2.7 +0.2±0.7 +0.9±1.7 +0.3±1.7 0.2±2.6
Conclusion: Our in vitro results confirmed that administration of n-3 PUFAs can inhibit colorectal cancer cell growth and enhance the cytotoxic effect of RT. However,
this inhibitory effect could not be reproduced in vivo in an animal model of xenografted colorectal tumour. Disclosure of Interest: F. Cai Grant/Research Support from: Foundation Nutrition 2000Plus, V. Granci Grant/Research Support from: Swiss National Science Foundation grant nº 310030 116738, M. Rouzaud: None declared, R. Miralbell: None declared, Y. Dupertuis Grant/Research Support from: Swiss National Science Foundation grant nº 310030 116738, C. Pichard Grant/Research Support from: Foundation Nutrition 2000Plus
PP073 MODULATORY EFFECTS OF POLYUNSATURATED FATTY ACIDS ON DIFFERENT CHEMOTHERAPEUTIC AGENTS V. Granci1 , F. Cai1 , Y.M. Dupertuis1 , C. Pichard1 . 1 Clinical Nutrition, University Hospital of Geneva, Geneva, Switzerland Rationale: Numerous evidences indicate an interest to combine chemotherapy with n-3 polyunsaturated fatty acids (n-3 PUFAs) in human cancers. We investigate the effects of fish oil (FO) (Omegaven® , Fresenius Kabi) and soybean oil (SO) (Lipoveneos® , Fresenius Kabi) emulsion enriched in n-3 PUFAs on conventional chemotherapeutical drugs such as irinotecan (CPT-11), Oxaliplatin and 5-Fluorouracil (5-FU). Methods: After treatment, viability of the human colorectal cancer cells HT-29 was evaluated using a MTT assay. Cell cycle and apoptosis was analyzed by flow cytometry with PI alone or combined with annexin-V, respectively. For analysis of caspase activation, Western blot analysis was applied. Results: A decrease in cell viability was observed when cells were treated with FO in combination with low doses of CPT-11, 5-FU or Oxaliplatin regardless of the incubation time. Table: HT-29 cell survival after a 48-h or 72-h chemotherapy w/o Fish oil or soybean oil emulsion as measured by MTT assay (*P < 0.05). Cell survival
48 h
Chemotherapy
Alone
+ FO
+ SO
Alone
73 h + FO
+ SO
5-FU CPT-11 Oxaliplatin
85.5±6.3 88.2±3 78.1±7.7
74.7±7.7 73.8±11* 59.1±4.9*
92.5±5.8 90.3±7.6 70.1±9.8
90±3.7 77.7±5.4 75.3±5.7
62.1±7.9* 64.7±4.6* 52.5±8.8*
84.7±12.7 70.2±9.1 66.8±9.1
Moreover, FO enhanced the pro-apoptotic effect of the three anti-cancer drugs compared with chemotherapy alone, as revealed by annexin V staining (P < 0.05). These observations were confirmed by analysis of caspase-3 expression showing the cleaved-caspase-3 product under FO and chemotherapy. Conclusion: These results indicate a specific synergy between n-3 PUFAs and anticancer agents commonly used in colorectal cancer chemotherapy. Further in vivo experiments are underway to highlight the mechanisms of action of such a combination for colorectal cancer chemotherapy. Disclosure of Interest: V. Granci Grant/Research Support from: Swiss National Science Foundation grant nº 310030 116738, F. CAI Grant/Research Support from: Foundation Nutrition 2000Plus, Y. Dupertuis Grant/Research Support from: Swiss National Science Foundation grant nº 310030 116738, C. Pichard Grant/Research Support from: Foundation Nutrition 2000Plus