Takehiro Shimada

Muscle volume loss after the induction of first-line chemotherapy as a novel prognostic factor in metastatic colorectal cancer patients.

558 Background: Muscle volume loss (MVL) is observed in end-stage cancer patients as cachexia. However, the impact of MVL on tumor response and survival still remains unclear during chemotherapy in metastatic colorectal cancer (mCRC) patients. The aim of this study is to evaluate correlation between MVL and oncologic outcomes in mCRC patients. Methods: A total of 91 mCRC patients who received first-line chemotherapy were identified in our prospective registry between February 2007 and April 2013. Skeletal muscle index at the level of L3 vertebra (SMI) was calculated by muscle volume normalized by stature at the time of the induction of first-line chemotherapy (bSMI) and first evaluation of tumor response (fSMI). Patients whose SMI decreased more than 10% were classified as MVL group. The impact of these variables on oncologic outcomes (overall survival [OS], progression free survival [PFS], and tumor response rate [RR]) were analyzed. Results: Mean bSMI and fSMI were 35.0 (SD: 7.11) cm2/m2, and 34.2 (SD: ...

Impact of liver fibrosis on effects and adverse effects of unresectable colorectal cancer under first line chemotherapy including CPT-11.

556 Background: Liver dysfunction is one of the irritating adverse effects in chemotherapy for colorectal cancer. Polymorphisms of UGTIA1, which is related to metabolism of CPT-11 in the liver, cause severe adverse events. In addition, long-term induction of CPT-11 may involve steatohepatitis. Thus, it is critical to surrogate liver dysfunction in chemotherapy including CPT-11. In this current study, we evaluated whether NAHLD fibrosis score (NFS) which is liver fibrosis marker of nonalcoholic steatohepatitis, is feasible for predicting the effects and adverse events of chemotherapy including CPT-11 for colorectal cancer. Methods: From January 2007 to May 2013, of 118 patients who were diagnosed with unresectable advanced/recurrent colorectal cancer in our hospital, we retrospectively analyzed 89 patients who underwent first line chemotherapy including CPT-11. We statistically analyzed the value of the pretreatment NFS on response rate (RR), progression-free survival (PFS), and hematologic or non-hematolo...

The impact of hepatic fiblosis on the incidence of liver metastasis from colorectal cancer.

529 Background: Non-alcoholic steatohepatitis (NASH) is closely associated with hepatic fibrosis (HF). The number of patients who have NASH is increasing by eating high-calorie diet. It remains unclear how much impact such NASH and HF on the development of liver metastasis by colorectal cancer (CRC). The objectives of this study is to clarify the influence of HF on metachronous liver-specific recurrence in colorectal cancer patients who underwent colorectal surgery with curative intent. Methods: Between 2000 and 2010, patients who underwent a curative surgical resection for CRC were included in this study. We evaluated the progression of HF by using non-alcoholic fatty liver disease fibrosis score (NFS) based on preoperative blood test result, age, BMI and DM. The patients with NFS higher than 0.676 were objectively defined as HF. The influence of HF on hepatic recurrence was assessed by survival analyses. Results: A total of 953 CRC patients were enrolled, comprised of 293 in stage I, 327 in stage II and...

PTH-289 The poor overall survival of right-sided colon cancer compared with left-sided colon cancers: a systematic review and meta-analysis

Introduction Right-sided colon cancers (RCC) and left-sided colon cancers (LCC) are of different embryological origins, and there are various differences between them. However, the survival difference has not been evaluated. The aim of the present study was to quantify the difference of prognosis between RCC and LCC by meta-analysis. Method PubMed and the Cochrane Library were searched during May 2014 for literature on right- versus left-sided colon cancers. The MeSH terms “colonic neoplasm” and the terms “prognosis” or “survival analysis” were combined with terms “left” and “right” or “sub site”. The effects of tumour locations on survival outcome (overall survival [OS] and cancer-specific survival [CSS]) were assessed. Hazard ratio (HR) was used as a surrogate for effect size, and random-effects meta-regression was applied as a method to evaluate the influences of covariates. Heterogeneity and publication bias were assessed. Results 15 studies (108,474 participants) which compared the prognosis of colon cancer according to tumour location were included. With respect to OS, patients with RCC had a significantly worse prognosis (HR = 1.14, 95% confidence interval [CI]: 1.06 –1.22, p < 0.01, I2= 41.82%) than those with LCC. Though, this tendency was not evident for CSS, which might be because CSS was evaluated by a small number of studies included in this analysis. Subgroup analyses demonstrated significant prognostic differences in Western countries (HR = 1.15, 95% CI: 1.08 – 1.23, p < 0.01), a nationwide database (HR = 1.15, 95% CI: 1.05 – 1.27, p = 0.01), and a stage-adjusted analysis (HR = 1.14, 95% CI: 1.05 – 1.24, p < 0.01). The test of funnel plot identified no publication bias. The source of heterogeneity was not identified in meta-regression. Conclusion Our findings indicate that tumour location is closely associated with prognosis in colorectal cancer patients, and those with RCC have a significantly worse prognosis than those with LCC in regards to OS. Therefore, RCC should be treated distinctively from LCC, and the establishment of standardised management for colon cancer by tumour location is needed. Disclosure of interest None Declared.

PTU-008 Is cranial to caudal approach a feasible technique for complete mesocolic excision (cme) in laparoscopic transverse colectomy?

Introduction Laparoscopic transverse colectomy (LTC) is one of the most challenging techniques because the region of its mesentery and lymph node (LN) dissection is controversial. In addition, anatomical anomalies are often observed in the root of middle colic artery (MCA), which is surrounded by critical vessels such as superior mesenteric vein (SMV), splenic vein (SPV) and inferior mesenteric vein (IMV). We believe that cranial to caudal approach is one of the answers against how to overcome the hurdle of CME and LN dissection in LTC because it’s relatively easy to discern the border of transverse colon mesentery from pancreas. Another is to clarify the dominantly feeding vessel and establish the interest region of lymphandectomy by using CT colonography and angiography preoperatively. Method First, we open the bursa omentalis widely through the gastrocolic ligament, and subsequently mobilise and take down the hepatic and splenic flexure. The anterior lobe of transverse mesocolon is then dissected at the inferior border of the pancreas with the so-called cranial to caudal approach. Right gastroepiploic vein (RGEV) is a landmark to reach SMV. Exposing pancreatic head and second potion of duodenum and blunt dissection are also important to take down hepatic flexure of transverse colon and detach mesentery of transverse colon. In the process, we transect one or two accessory right colonic vein (ARCV). With skeletonizing SMV to proximal side, merging of SMV, SPV and IMV are uncovered. We think it’s critical to harvest the lymph nodes completely in the region enclosed by SMV, SPV and IMV where there should be generally the root of MCA. CT angiography is a robust support to comprehensively recognise the vessel anatomical anomalies and dissected region of colon mesentery. Continuously, it’s possible to dissect the root of ileocolic and right colic vessels with skeletonizing ventral surface of SMA and SMV in this approach. Results We herein present our practical laparoscopic transverse colectomy with LN dissection in video as attatched to demonstrate our concept and strategy in this field. Conclusion We think that cranial to caudal approach is a feasible technique for complete mesocolic excision in laparoscopic transverse colectomy. Disclosure of interest None Declared.

Abstract 4552: Apatorsen enhances 5-FU sensitivity in colon cancer cell SW480

[Background] Heat Shock Protein (HSP) 27 is a chaperone protein of small molecular weight, which protects cells in response to various stresses. Previously we elucidated that HSP27 was a key molecule in determining 5-Fluorouracil (5-FU) resistance in colorectal cancer (CRC). Thus, apatorsen, an antisense oligonucleotide that suppresses HSP27 levels intracellularly, might overcome 5-FU resistance in CRC. In this basic research, we evaluated the feasibility of adding apatorsen with 5-FU against CRC. [Methods] Human CRC cell line SW480 was treated with apatorsen (1nM, 10nM, 100nM) for 48 hours continuously. HSP27 protein level was determined by immunoblot and densitometry analysis. Next, the cells were exposed by various concentrations of 5-FU for 48 hours following treatment with apatorsen. The in vitro growth inhibition rates (IR) were assessed by MTT assay and we evaluated the change of 5-FU resistance, which was estimated as the drug concentration inducing 50% IR (IC50). [Results] Apatorsen (0, 1, 10, 100nM) successfully suppressed HSP27 protein levels (100, 86.6, 61.0, 50.5%) in a dose-dependent manner. In cell viability assays, apatorsen changed the IC50 of 26.65μg/ml in control into 15.55 (58.3%), 11.28 (42.3%), and 9.18 (34.4%) respectively. [Summaries] Apatorsen significantly enhanced 5-FU sensitivity in the CRC cell line SW480 by suppressing HSP27 levels. HSP27 may serve as a reliable target in enhancing 5-FU chemotherapy for CRC. Therefore, apatorsen is a promising treatment requiring further investigation. Citation Format: Takehiro Shimada, Masashi Tsuruta, Shingo Akimoto, Kaoru Koishikawa, Koji Okabayashi, Hirotoshi Hasegawa, Yuko Kitagawa. Apatorsen enhances 5-FU sensitivity in colon cancer cell SW480. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4552. doi:10.1158/1538-7445.AM2015-4552