Search

The number of lymph node metastasis (LNM) is a strong prognostic factor in the treatment of colorectal cancer (CRC). However, the impact of the mesentery location on LNM remains unclear. We assessed the impact LNM location on the recurrence of stage III CRC.Subjects with CRC and pathologically positive LNM were enrolled retrospectively. We defined three groups: LNM adjacent to the tumour (group A), metastases with horizontal or vertical spread (group B), and metastases with both horizontal and vertical spread (group C). Recurrence-free survival (RFS) was the primary outcome measure used for the study.A total of 241 (Group A: 121, B: 90, and C: 30) patients were recruited for the study. Multivariate analysis by Cox regression model indicated LNM location to be an independent predisposing risk factor for recurrence [group B: Hazard ratio (HR) 2.01, 95% Confidential interval (CI) 1.12-3.60, P = 0.019; group C: HR 3.00, 95% CI 1.34-6.72, P = 0.008]. Addition of mesentery spread to the N classification was significant risk factor for recurrence (mN2a: HR 2.01, 95% CI 1.07-3.78, P = 0.029; mN2b: HR 3.96, 95% CI 2.12-7.40, P 0.01). Comparison of Harrell's C-index values was conducted, and the modified N staging risk was 0.6377, whereas the TNM N stage classification was 0.5869.Mesentery location of LNM was a risk factor and consideration of it might be beneficial for accurate prediction of CRC prognosis.

Metformin has been reported to be associated with improved cancer prognosis when used in combination with chemotherapy and/or radiotherapy. In this study, we present a systematic review and meta-analyses of studies evaluating the association of tumor pathological response with the use of metformin during neoadjuvant chemoradiotherapy (NACRT) in rectal and esophageal/gastroesophageal cancer patients.We systematically searched databases for articles that compared concurrent metformin use with no metformin use in cancer patients treated with NACRT following the PRISMA 2020. The design and quality of the collected studies were reviewed, and meta-analyses were performed on the pathologic complete response (pCR) rate, tumor regression grade (TRG), T factor downstaging, and N factor downstaging.Three databases were searched, and 220 papers were screened. Five retrospective cohort study papers were eligible for the meta-analysis, with a total of 2041 patients. The included papers contained only rectal and esophageal/gastroesophageal cancers. In the metformin group, the pCR rate was 26% [20-32%], and metformin was associated with the pCR rate (odds ratio [OR] = 0.51 [0.34-0.76], p 0.01). Meta-regression analysis of the pCR rate showed a positive correlation with adenocarcinoma (coefficient = 0.13 [0.02-0.25], p = 0.03) and fluoropyrimidine anticancer drug use (coefficient = 0.01 [0.001-0.02], p = 0.03).The results suggest that metformin is associated with pCR rate when used in combination with NACRT. The association of metformin and pCR rate in combination with fluoropyrimidine anticancer drugs was observed mostly for adenocarcinoma patients.

Objective The relationship between preoperative mean corpuscular volume and postoperative prognosis has been reported in some cancers recently, but no certain consensus has been reached, especially for colorectal cancer. We evaluated the usefulness of mean corpuscular volume as a prognostic factor in colorectal cancer patients. Methods This study included 1003 patients with colorectal cancer who underwent curative surgery in a single institution. The relationship between mean corpuscular volume values and postoperative recurrence was evaluated by fractional polynomial model. Based on the result, patients were divided into groups according to mean corpuscular volume values. Clinicopathological factors and long-term outcomes were compared between the groups. Results The risk of postoperative recurrence according to mean corpuscular volume value showed a J-shaped curve, suggesting that both low and high mean corpuscular volume have high risk. Low mean corpuscular volume (≤84 fl) group was oncologically advanced in terms of pathological tumor stage, histological grade and lymphatic invasion with higher inflammation markers. High mean corpuscular volume (>95 fl) group had higher frequency of drinking habit with higher values of aspartate aminotransferase, alanine aminotransferase and γ-glutamyl transpeptidase. Abnormal mean corpuscular volume group including these two groups showed significantly worse disease-free survival than the other (P < 0.001). Multivariate analysis suggested that abnormal mean corpuscular volume was an independent risk factor for postoperative recurrence (hazard ratio, 1.344; 95% confidence interval, 1.005–1.796; P = 0.046). Furthermore, its prognostic impact was more significant in pStage III than in other stages. Conclusion Preoperative low and high mean corpuscular volume is a poor prognostic factor in colorectal cancer patients. It could be a predictive marker to estimate worse survival outcome after surgery.

STAT3 is involved in the progression of several cancers, and has been proposed as target for therapy. Indeed, the multitargeted tyrosine kinase inhibitor drug regorafenib, which indirectly inhibits STAT3, can significantly enhance the effects of anti-programmed death receptor (PD)-1 therapy in hepatocellular carcinoma (HCC) models. Here, we studied the impact of a direct STAT3 inhibitor on the tumor microenvironment and PD-1 blockade efficacy in HCC models.Orthotopic mouse models of HCC (RIL-175 and HCA-1 grafts in syngeneic mice) were used to test the efficacy of the selective STAT3 inhibitor STX-0119 alone or combined with anti-PD-1 antibodies. We evaluated the effects of therapy on tumor vasculature and the immune microenvironment using immunofluorescence (IF), cell viability assay and quantitative real-time (qRT)-PCR in tumor tissues.Combining anti-PD-1 antibodies with a STX-0119 failed to show a growth delay or survival benefit compared to each agent alone or control in any of the HCC models. Interestingly, evaluation of intratumoral CD8+ T cell infiltration by IF showed a significant increase after one-week treatment with STX-0119 (p=0.034). However, STX-0119 treatment simultaneously promoted increased immunosuppression in the tumor microenvironment by increasing the proportion of Tregs, tissue hypoxia and α-SMA activated cancer-associated fibroblasts (CAFs) measured by IF. Consistent with these findings, we found increased immature tumor vessels by IF and VEGF, Tgf-β and Vash2 expression by qPCR.Pharmacologic STAT3 inhibition could significantly enhance CD8

Aim: To evaluate the significance of next-generation sequencing-based gene panel testing in surgically resectable colorectal cancer by analyzing real-world data. Materials & methods: A total of 107 colorectal cancer patients who underwent curative surgery were included, and correlations between next-generation sequencing data and clinicopathological findings were evaluated. Results: More combination patterns in gene alteration were identified in advanced-stage tumors than in early-stage tumors. The copy number alteration count was significantly lower in right-sided colon tumors and early-stage tumors. Homologous recombination deficiency was more often identified in advanced-stage tumors, and high homologous recombination deficiency status was useful for identifying high-risk stage II tumors. Conclusion: Homologous recombination deficiency was identified as a useful result of gene panel testing with novel utility in clinical practice.

The present study assessed postoperative bowel dysfunction in Japanese patients with rectal cancer, including patients who underwent preoperative radiotherapy (RT).A total of 277 rectal cancer patients who underwent primary resection were included in the analyses. A questionnaire survey was administered using the low anterior resection syndrome (LARS) score and Wexner score. Scores were determined one year after rectal surgery or diverting ileostomy closure. The LARS score was categorized as minor LARS (21-29) and major LARS (30-42).The proportions of patients with minor and major LARS were significantly larger and Wexner scores significantly higher in patients with distal tumors and a lower anastomosis level than in those with proximal tumors and a higher anastomosis level. Among the patients with lower rectal cancer, the proportions with minor and major LARS were similar between those with and without preoperative RT. The Wexner scores in patients with preoperative RT were significantly higher than in patients without RT. A distal tumor location and lower anastomosis level were independent risk factors of major LARS in multivariate analyses.A distal tumor location, low anastomosis level, and preoperative RT might be associated with postoperative bowel dysfunction in rectal cancer patients.

Purpose: This study aimed to evaluate the significance of Next-generation sequencing (NGS)-based gene panel testing in resectable colorectal cancers (CRC)s by analyzing real-world data collected prospectively from patients. Methods: Patients with CRC who underwent surgery from July 2018 to February 2020 at our institution were included, and correlations between various NGS data and clinicopathological findings were evaluated. Results: Overall, 107 patients were included in this study. The tumor stage was I in 28 cases (26.2%), II in 40 cases (37.4%), III in 32 cases (29.9%), and IV in 7 cases (6.5%). Actionable gene alterations were found in 97.2% of the cases. Co-alteration analysis suggested that either TP53- or APC-related alterations were more frequently found in early-stage tumors (stage I). The copy number alteration count was significantly lower in right side colon tumors than in tumors in other locations (P < 0.05). Homologous recombination deficiency (HRD) was more often identified in stage IV tumors than in stage I or II tumors (P < 0.05). Moreover, high HRD status was suggested to be useful for identifying high-risk stage II tumors (P < 0.05). Conclusion: In this study, real-world NGS data represented the biological features of CRCs. HRD was identified as a useful result of gene panel testing with novel utility in clinical practice.

The present study aimed to investigate whether side-to-end anastomosis could provide an improved surgical outcome, such as lower anastomotic leakage rate, compared with end-to-end anastomosis, following anterior resection for rectal and rectosigmoid cancer. This retrospective study included 162 patients with rectal cancer who underwent elective anterior resection between January 2012 and October 2019 at a single institution. Patients with double cancers or colonic J-pouch were excluded. Anastomotic leakage was defined clinically and radiologically. Side-to-end anastomosis was introduced in the International University of Health and Welfare Mita Hospital in January 2017. Side-to-end anastomosis was performed in 63 patients, while end-to-end anastomosis was performed in 99 patients. Tumors tended to be located lower in the rectum in the side-to-end anastomosis group than in the end-to-end anastomosis group. No significant differences were observed in other patient characteristics. The incidence of anastomotic leakage was significantly lower in the side-to-end anastomosis group than in the end-to-end anastomosis group (3/63, 4.8% vs. 18/99, 18.2%, respectively, P=0.02). No significant differences were observed in the incidence rates of other complications. Univariate and multivariate analyses revealed that a smoking habit (P=0.04) and side-to-end anastomosis (P=0.02) were significantly associated with anastomotic leakage. In conclusion, side-to-end anastomosis using a double-stapling technique following anterior resection for rectal cancer may prevent anastomotic leakage.

Purpose Angiopoietin-like 4 (ANGPTL4) was recently shown to be associated with cancer progression but little is known about its contribution to cancer metabolism. The purpose of this study was to elucidate the role of ANGPTL4 in glucose metabolism in colorectal cancer (CRC). Methods Immunohistochemical staining of CRC specimens classified 84 patients into two groups according to ANGPTL4 expression. Clinicopathological characteristics, gene mutation status obtained by next-generation sequencing, and fluorodeoxyglucose (FDG) uptake measured by positron emission tomography/computed tomography (PET/CT) were compared between the two groups. Furthermore, the impact of ANGPTL4 expression on cancer metabolism was investigated by a subcutaneous xenograft mouse model using the ANGPTL4 knockout CRC cell line and glucose transporter (GLUT) expression was evaluated. Results There were significantly more cases of T3/4 tumours (94.3% vs. 57.1%, P < 0.001) and perineural invasion (42.9% vs. 22.4%, P = 0.046) in the ANGPTL4-high group than in the low group. Genetic exploration revealed a higher frequency of KRAS mutation (54.3% vs. 22.4%, P = 0.003) in the ANGPTL4-high tumours. All the FDG uptake parameters were significantly higher in ANGPTL4-high tumours. In vivo analysis showed a significant reduction in tumor size due to ANGPTL4 knockout with lower expression of GLUT1 and GLUT3, and suppression of AKT phosphorylation. Conclusion ANGPTL4 regulates the expression of GLUTs by activating the PI3K-AKT pathway and thereby promoting glucose metabolism in CRC. These findings establish a new functional role of ANGPTL4 in cancer progression and lay the foundation for developing a novel therapeutic target.

Lavage cytology is a method to detect cancer cells released within the abdominal cavity. It has been widely utilized, in particular, for gastric cancer. However, its clinical significance has not yet been determined in colorectal cancer.This study aimed to investigate the frequency of lavage cytology positivity and its influence on the prognosis of patients with colorectal cancer.This is a single-institution retrospective observational study.This study was conducted at a comprehensive cancer center.We retrospectively analyzed 3135 colorectal cancer cases from 2007 to 2013 at our institution. Intraoperative peritoneal washing cytology was performed just after the start of the operation. Fluids were centrifuged for 5 minutes at 2500 rotations per minute, cell pellets were smeared on microscope glass slides, and Papanicolaou staining was performed.The primary outcome was the 5-year overall survival rate. The secondary outcome was the 5-year recurrence rate.Lavage cytology positivity was detected in 19 (2.0%) and 86 (16.9%) cases of stage III and IV colorectal cancer; however, no positive cases were found in stage I and II colorectal cancer. Lavage cytology positivity was an independent prognostic factor in stage III and IV colorectal cancer in the multivariate analysis (5-year mortality HR 3.59 [1.69-7.64] in stage III, 2.23 [1.15-4.31] in stage IV). The prognosis of the 5-year survival rate was significantly worse in the lavage cytology-positive group in stages III and IV. In terms of recurrence, the results of the lavage cytology-positive group in stage III were similar to those of the lavage cytology-positive/negative group in stage IV (73.7%, 70.0%, and 75.0%).This study was limited by its retrospective study design.Lavage cytology positivity is an independent prognostic and regulatory factor of stage IV colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B770.INCIDENCIA Y VALOR PRONÓSTICO EN LA CITOLOGÍA DEL LAVADO PERITONEAL EN CÁNCER COLORECTALANTECEDENTES:La citología del lavado peritoneal es un método para detectar células cancerosas liberadas dentro de la cavidad abdominal. Se ha utilizado ampliamente, en particular para el cáncer gástrico. Sin embargo, aún no se ha determinado su importancia clínica en el cáncer colorrectal.OBJETIVO:Este estudio tuvo como objetivo investigar la frecuencia de positividad de la citología del lavado y su influencia en el pronóstico de los pacientes con cáncer colorrectal.DISEÑO:Este fue un estudio observacional retrospectivo de una sola institución.DISENTORNO CLÍNICO:El estudio se llevó a cabo en un centro oncológico integral.PACIENTES:Analizamos retrospectivamente 3.135 casos de cáncer colorrectal desde 2007 hasta 2013 en nuestra institución. La citología de lavado peritoneal intraoperatorio se realizó inmediatamente después del inicio de la operación. Los fluidos se centrifugaron durante 5 min a 2.500 rpm, los sedimentos celulares se extendieron sobre portaobjetos de vidrio de microscopio y se realizó la tinción con Papanicolaou.DISPRINCIPALES MEDIDAS DE VALORACIÓN:El primer resultado fueron las tasas de supervivencia general a 5 años. El segundo resultado las tasas de recurrencia a los 5 años.RESULTADOS:Se detectó positividad en la citología de lavado en 19 (2,0%) y 86 (16,9%) casos de cáncer colorrectal en estadio III y IV, respectivamente; sin embargo, no se encontraron casos positivos en el cáncer colorrectal en estadio I y II. La positividad de la citología de lavado fue un factor pronóstico independiente en el cáncer colorrectal en estadio III y IV en el análisis multivariado [cociente de riesgo de mortalidad a 5 años 3,59 (1,69-7,64), en estadio III, 2,23 (1,15-4,31), en estadio IV]. El pronóstico de la tasa de supervivencia a 5 años fue significativamente peor en el grupo con citología de lavado positiva en los estadios III y IV. En cuanto a la recurrencia, los resultados del grupo de lavado con citología positiva en el estadio III fueron similares a los del grupo de lavado con citología positiva / negativa en el estadio IV (73,7%, 70,0% y 75,0%).LIMITACIONES:Este estudio estuvo limitado por su diseño de estudio retrospectivo.CONCLUSIONES:La positividad de la citología de lavado es un factor pronóstico y regulador independiente del cáncer colorrectal en estadio IV. Consulte Video Resumen en http://links.lww.com/DCR/B770. (Traducción- Dr. Ingrid Melo).

Laparoscopic surgery is a minimally invasive and frequently performed surgical procedure that has become the standard surgery for colorectal cancer. Needlescopic surgery (NS) for colon cancer has also been performed and reported as a less invasive technique. In this study, we investigated the long-term outcomes of NS in comparison with those of conventional surgery (CS). The data of 1122 patients without distant metastasis who underwent laparoscopic surgery between 2011 and 2014 were retrospectively analyzed. In this study, NS was defined as a laparoscopic procedure performed with the use of 3-mm ports and forceps with one 5-mm port for an energy device, as well as with clips. One 12-mm port was placed in the umbilicus for specimen extraction from the abdominal cavity. A total of 241 patients underwent NS. There was no significant difference between the 5-year recurrence rate and the 5-year total mortality rate (NS: 10.0% and 5.4% vs. CS: 10.3% and 3.5%, p = 0.86/0.23). In the multivariate analysis, NS was not found to be an independent prognostic factor. In terms of the distribution of recurrence sites, there was no significant difference between the two groups. NS for colon cancer was not inferior to CS in terms of short-term and long-term outcomes.

The incidence of colorectal cancer (CRC) has been on the rise, which is linked to the increasing prevalence of obesity, based on global epidemiological evidence. Although chronic inflammation is implicated in tumor development, the mechanisms underlying obesity‐associated CRC remain unknown. Here, we sought to identify the inflammatory cytokines and their roles in obesity‐related colorectal tumorigenesis using cytokine array analyses in a mouse model. Colorectal tumorigenesis was induced through i.p. injection of azoxymethane once a week for 6 weeks in 6‐week‐old female WT C57Black/6J mice and the obesity diabetes model mouse KK/TaJcl, KK‐Ay/TaJcl. The formation of aberrant crypt foci and colorectal tumors were more frequent in obese mice compared with WT mice, and both serum interleukin (IL)‐13 and IL‐13 receptor (R) expression in the normal intestinal mucosal epithelium were significantly increased in the obese mice. Furthermore, addition of IL‐13 to a human CRC cell line and a human colon organoid culture altered the phenotype of intestinal epithelial cells. Knockdown experiments further revealed that IL‐13Rα1 dominantly induced mucosal proliferation. Collectively, These results suggest an association between anti‐inflammatory cytokines and colorectal carcinogenesis, and provide new research directions for cancer prevention strategies. In particular, inflammation provoked by obesity, notably by increased expression of the cytokine IL‐13, could play an important role in the carcinogenesis of obesity‐related CRC.

We compared triangulating anastomosis (TRI) with functional end-to-end anastomosis (FEEA) in terms of patient demographics, clinicopathological features, and short- and long-term outcomes in this study. From November 2005 to May 2016, 315 patients with transverse colon cancer underwent laparoscopic resection. TRI was performed in 62 patients and FEEA in 253 patients. Patients with another concomitant cancer, who received neoadjuvant chemotherapy, and/or who underwent another operation at the same time were excluded. The patients’ backgrounds were comparable in each group. Transverse colectomy was selected more frequently in TRI and right hemicolectomy in FEEA. The operation time was shorter in TRI. The rate of anastomotic leakage was comparable (1.6% in TRI vs. 0.8% in FEEA). Stricture was more common in TRI (8.1% vs. 0%) and bleeding was more common in FEEA (1.6% vs. 10.6%). The rate of long-term complications was comparable in each group. Overall survival of stage 0–III patients was comparable in each group (94.7% in TRI vs. 93.7% in FEEA). 5-year disease-free survival of stage 0–III, stage II, and stage III patients was also comparable in each group (94.8% vs. 93.0%, 100% vs. 92.1%, and 80.3% vs. 79.2% in TRI and FEEA, respectively). The short- and long-term outcome rates were acceptable in both groups. Specific attempts to prevent complications are required for each anastomotic procedure.

The lymphatic system is known to be the primary pathway of metastasis for colorectal cancer. However, beyond regional lymph node metastases, little is known about the pathway of lymphatic metastases and the differences in the recurrence site risk. The aim of this study was to clarify the relationship between lymph node metastasis and the first recurrence site in colorectal cancer.Patients with colorectal cancer who underwent curative resection in our institution between January 2003 and December 2016 were included in this analysis. The relationship between the first recurrence site and clinicopathological factors was analyzed by the Cox regression model and competing risk regression model.In total, 1,249 patients with colorectal cancer were included in this analysis. We found that the stages of lymph node metastases (N0 vs N1: P = .008, N0 vs N2a: P.001, N0 vs N2b: P.001) were significantly associated with lung metastasis in the multivariate analysis. Furthermore, in the competing risk analysis, the stages of lymph node metastases were significantly correlated with lung metastasis (N0 vs N1: P = .002, N0 vs N2a: P.001, N0 vs N2b: P.001) but were not correlated with other recurrence sites.The severity of lymph node involvement had a strong correlation with lung metastases in patients with colorectal cancer.

BACKGROUND Appendiceal tumor has recently been treated differently from colorectal cancer. However, obtaining knowledge of this disease is difficult because of its rareness. OBJECTIVE This study aimed to investigate the clinicopathological characteristics of appendiceal tumors in a Japanese cohort. DESIGN This was a nationwide multi-institution retrospective observational study. SETTING This study was conducted at the participating tertiary referral hospitals. PATIENTS Patients with appendiceal tumor who were diagnosed between 2000 and 2017 were included. MAIN OUTCOME MEASURES The primary outcome measured was the total survivability. RESULTS A total of 922 patients from the 43 facilities that participated were identified. Of these, 114 patients were diagnosed with cancer other than adenocarcinomas. The remaining 760 patients, with the exception of 48 patients with unknown survival data, were eligible for the final cohort analysis. Of these 760 patients, 515 (67.8%) had mucinous adenocarcinomas and 245 (32.2%) had nonmucinous adenocarcinomas. Within the mucinous adenocarcinoma group, 267 patients (35.1%) were diagnosed as having low-grade appendiceal mucinous neoplasm. The 5-year survival rate of mucinous adenocarcinoma (83.1%) was superior to that of nonmucinous adenocarcinoma (62.0%; p < 0.01). Regarding mucinous adenocarcinoma, multivariate analysis revealed that high differentiation grade (American Joint Committee on Cancer grade 2/3), distant metastases, and R2 operation were significantly associated with a higher 5-year mortality rate. The 5-year survival rate was significantly better for low-grade appendiceal mucinous neoplasms (93.3%) than for other mucinous adenocarcinomas (72.1%; p < 0.01). LIMITATIONS This study was limited by its retrospective study design. CONCLUSIONS We cumulatively investigated appendiceal tumors in a multicenter retrospective study; this is the first such report from Asia. Grouping the grades as per the American Joint Committee on Cancer was useful as a prognostic indicator of appendiceal mucinous adenocarcinomas, including low-grade appendiceal mucinous neoplasm. See Video Abstract at http://links.lww.com/DCR/B282. ANALISIS DE LAS CARACTERISTICAS CLINICOPATOLOGICAS DE LOS TUMORES APENDICULARES EN JAPON: UN ESTUDIO CLINICO RETROSPECTIVO COLABORATIVO MULTICENTRICO: UNA ENCUESTA NACIONAL JAPONESA: El tumor apendicular recientemente se ha tratado de manera diferente al cancer colorrectal. Sin embargo, obtener conocimiento de esta enfermedad es dificil debido a su rareza.Este estudio tuvo como objetivo investigar las caracteristicas clinicopatologicas de los tumores apendiculares en una cohorte Japonesa.Este fue un estudio observacional retrospectivo de multiples instituciones a nivel nacional.Este estudio se realizo en los hospitales de referencia terciarios participantes.se incluyeron pacientes con tumor apendicular que fueron diagnosticados entre el 2000 y 2017.El resultado primario medido fue la supervivencia total.Se identificaron un total de 922 pacientes de las 43 instalaciones que participaron. De estos, 114 pacientes fueron diagnosticados con cancer distinto de adenocarcinomas. Los 760 pacientes restantes, excepto 48 pacientes con datos de supervivencia desconocidos, fueron elegibles para el analisis de cohorte final. De estos 760 pacientes, 515 (67,8%) tenian adenocarcinomas mucinosos y 245 (32,2%) tenian adenocarcinomas no mucinosos. Dentro del grupo de adenocarcinoma mucinoso, 267 pacientes (35,1%) fueron diagnosticados con neoplasia mucinica apendicular de bajo grado (LAMN). La tasa de supervivencia a 5 anos del adenocarcinoma mucinoso (83.1%) fue superior a la del adenocarcinoma no mucinoso (62,0%) (p

To evaluate the prognostic value of the comprehensive risk score (CRS) of the Estimation of Physiologic Ability and Surgical Stress for managing patients with colorectal cancer (CRC) who underwent elective and emergency colorectal cancer surgery with curative intent.CRS, which is calculated based on both clinical and surgical factors, is a good predictor of postoperative complications and mortality. However, the impact of CRS in CRC prognosis remains unclear.Patients with CRC who underwent curative resection between 2010 and 2019 were retrospectively enrolled in this study. The cohort was divided into the low and high CRS groups. The prognostic value of CRS was evaluated via Cox regression and Kaplan-Meier analyses. The CRS cutoff value was obtained using the Youden index applied to OS curves and have not been validated by any validation cohorts.In total, 2407 patients, including 1359 and 1048 patients with low and high CRS, respectively, were enrolled in this study. Multivariate analysis revealed that a CRS was an independent prognostic factor of overall and recurrence-free survival regardless of disease stage. Furthermore, adjuvant chemotherapy was beneficial for the survival of patients with stage III CRC in both high and low CRS groups; however, the survival benefit was limited in elderly high CRS patients.CRS was a strong prognostic factor for CRC regardless of disease stage and might be considered as a biomarker for selecting elderly patients who are eligible for adjuvant chemotherapy.

Background Although R0 surgery is recommended for stage IV colorectal cancer, the degree of required lymphadenectomy has not been established. The aim of this study was to investigate the prognostic impact of high ligation (HL) of the feeding artery and the number of retrieved lymph nodes after R0 surgery for colorectal cancer and synchronous colorectal cancer liver metastasis (CRLM). Methods This was a multi‐institutional retrospective analysis of patients with colorectal cancer and synchronous CRLM who had R0 surgery between January 1997 and December 2007. Clinical and pathological features were compared in patients who underwent HL and those who had a low ligation (LL). Kaplan–Meier analysis was performed to estimate the effect of HL on overall survival (OS). The impact of several risk factors on survival was analysed using the Cox proportional hazards model. Results Of 549 patients, 409 (74·5 per cent) had HL. Median follow‐up was 51·4 months. HL significantly improved the 5‐year OS rate (58·2 per cent versus 49·3 per cent for LL; P = 0·017). Multivariable analysis revealed HL to be a significant prognostic factor compared with LL (5‐year mortality: hazard ratio (HR) 0·68, 95 per cent c.i. 0·51 to 0·90; P = 0·007). In subgroup analysis, the positive effect of HL on OS was greatest in patients with lymph node metastasis. Conclusion HL of the feeding artery was associated with improved OS in patients with colorectal cancer and synchronous CRLM after R0 surgery., Although R0 surgery is recommended for stage IV colorectal cancer, the degree of lymphadenectomy required has not been established. A multi‐institutional retrospective analysis was done of patients with colorectal cancer and synchronous hepatic metastases who were treated with R0 surgery. More aggressive lymphadenectomy could improve the overall survival of these patients. High ligation improves survival.

Laparoscopic surgery is a minimally invasive and frequently performed surgical procedure that has become the standard surgery for colorectal cancer. Needlescopic surgery (NS) for colon cancer has also been performed and reported as a less invasive technique. In this study, we investigated the long-term outcomes of NS in comparison with those of conventional surgery (CS).The data of 1122 patients without distant metastasis who underwent laparoscopic surgery between 2011 and 2014 were retrospectively analyzed. In this study, NS was defined as a laparoscopic procedure performed with the use of 3-mm ports and forceps with one 5-mm port for an energy device, as well as with clips. One 12-mm port was placed in the umbilicus for specimen extraction from the abdominal cavity.A total of 241 patients underwent NS. There was no significant difference between the 5-year recurrence rate and the 5-year total mortality rate (NS: 10.0% and 5.4% vs. CS: 10.3% and 3.5%, p = 0.86/0.23). In the multivariate analysis, NS was not found to be an independent prognostic factor. In terms of the distribution of recurrence sites, there was no significant difference between the two groups.NS for colon cancer was not inferior to CS in terms of short-term and long-term outcomes.

This is the first report of laparoscopic-endoscopic cooperative surgery (LECS) for an ileal tumor. A 50-year-old man was admitted to our hospital with a positive fecal occult blood test. Colonoscopy detected a submucosal tumor with intussusception located in the ileum, 10 cm oral from the Bauhin valve. On further examination, he was diagnosed with an ileal lipoma. There were no signs of malignancy. LECS was performed for the ileal tumor. After submucosal elevation by injecting saline solution, a mucosal incision was made circumferentially along the tumor. A full-thickness incision was created endoscopically and laparoscopically on the circumferential mucosal incisional line. The tumor was withdrawn intraluminally by endoscopy. The defect of the ileal wall was closed laparoscopically in an axial direction with linear staplers. Histologically, the tumor was a 25-mm ileal lipoma with negative resection margins and no malignancy.

Tumor draining lymph nodes (TDLNs) are located in the routes of lymphatic drainage from a primary tumor and have the highest risk of metastasis in various types of solid tumors. TDLNs are also considered as a tissue to activate the antitumor immunity, where antigen-specific effector T cells are generated. However, T cell receptor (TCR) repertoires in TDLNs have not been well characterized. We collected 23 colorectal cancer tumors with 203 lymph nodes with/without metastatic cancer cells (67 were metastasis-positive and the remaining 136 were metastasis-negative) and performed TCR sequencing. Metastasis-positive TDLNs showed a significantly lower TCR diversity and shared TCR clonotypes more frequently with primary tumor tissues compared to metastasis-negative TDLNs. Principal component analysis indicated that TDLNs with metastasis showed similar TCR repertoires. These findings suggest that cancer-reactive T cell clones could be enriched in the metastasis-positive TDLNs.

Introduction The lateral approach is the standard for laparoscopic splenectomy. However, when the modified Hassab's operation is performed laparoscopically, the patient is placed in the supine position and then the right semi-lateral or lateral decubitus position. Based on our experience with laparoscopic adrenalectomy and splenectomy, we laparoscopically performed the modified Hassab's operation with the patient in the right lateral decubitus position. Materials and Surgical Technique Indications for the modified Hassab's operation for patients with portal hypertension in our institute include both gastric varices and hypersplenism resistant to endoscopic or radiologic procedures. We performed splenectomy and devascularization of the greater curvature and then dissected adhesions between the stomach, pancreas, and gastrohepatic ligament. With the patient in the right lateral decubitus position, the lesser curvature could be identified from both the ventral and dorsal sides. Discussion For the modified Hassab's operation, as in laparoscopic gastrectomy, many operators select the supine position for lesser curvature devascularization and gastric vessel ligation. However, after sufficient adhesion dissection around the stomach, anatomical structures can be identified in the right lateral decubitus position. For this approach, gravity is not an issue on the dorsal side, and the lesser curvature can be observed from both the ventral and dorsal sides with the patient in the right lateral decubitus position. Laparoscopically performing the modified Hassab's operation with the patient in the right lateral decubitus position is a feasible method.

Introduction Spigelian hernia (SH) is a rare ventral hernia occurring near the lateral border of the rectus muscle. The treatment remains controversial and depends on institutional expertise. Although laparoscopic surgery is a good adaptation for the repair of ventral hernias, only a few cases have been reported in the literature. Here, we report a case of totally extra-peritoneal (TEP) repair for bilateral SHs. Presentation of case A 74-year-old Japanese man presented with asymptomatic bulges in the right lower abdominal quadrant. On physical examination, the bulges were located to the right of the lateral border of the abdominal rectus muscle and the right inguinal region in an upright position. We diagnosed right SH and coincident homonymous ipsilateral inguinal hernia (IH) by abdominal computed tomography and planned a curative operation by laparoscopy. By first laparoscopic exploration, we found an asymptomatic SH to the left of the lateral border of the abdominal rectus muscle and performed TEP repair for all hernias. The second laparoscopic exploration after fixing the mesh in place revealed that the orifice of the right SH was scarred and stiffened by repeated prolapse. We finally eliminated the sac by ligation because of a fear causing of reduction en masse of the SH. Discussion and conclusion The use of laparoscopy simplified the diagnosis and facilitates the subsequent repair of the hernia. TEP approach is the ideal treatment for the simultaneous laparoscopic repair of SH and IH.

Highlights • Laparoscopic exploration is important to precise diagnosis of ventral hernia. • Laparoscopic totally extra-peritoneal repair is feasible for Spigelian hernia. • Laparoscopic exploration is also important after repairing ventral hernia. • Abdominal CT in the abdominal position is useful to precise diagnosis of hernia., Introduction Spigelian hernia (SH) is a rare ventral hernia occurring near the lateral border of the rectus muscle. The treatment remains controversial and depends on institutional expertise. Although laparoscopic surgery is a good adaptation for the repair of ventral hernias, only a few cases have been reported in the literature. Here, we report a case of totally extra-peritoneal (TEP) repair for bilateral SHs. Presentation of case A 74-year-old Japanese man presented with asymptomatic bulges in the right lower abdominal quadrant. On physical examination, the bulges were located to the right of the lateral border of the abdominal rectus muscle and the right inguinal region in an upright position. We diagnosed right SH and coincident homonymous ipsilateral inguinal hernia (IH) by abdominal computed tomography and planned a curative operation by laparoscopy. By first laparoscopic exploration, we found an asymptomatic SH to the left of the lateral border of the abdominal rectus muscle and performed TEP repair for all hernias. The second laparoscopic exploration after fixing the mesh in place revealed that the orifice of the right SH was scarred and stiffened by repeated prolapse. We finally eliminated the sac by ligation because of a fear causing of reduction en masse of the SH. Discussion and conclusion The use of laparoscopy simplified the diagnosis and facilitates the subsequent repair of the hernia. TEP approach is the ideal treatment for the simultaneous laparoscopic repair of SH and IH.

The lateral approach is the standard for laparoscopic splenectomy. However, when the modified Hassab's operation is performed laparoscopically, the patient is placed in the supine position and then the right semi-lateral or lateral decubitus position. Based on our experience with laparoscopic adrenalectomy and splenectomy, we laparoscopically performed the modified Hassab's operation with the patient in the right lateral decubitus position.Indications for the modified Hassab's operation for patients with portal hypertension in our institute include both gastric varices and hypersplenism resistant to endoscopic or radiologic procedures. We performed splenectomy and devascularization of the greater curvature and then dissected adhesions between the stomach, pancreas, and gastrohepatic ligament. With the patient in the right lateral decubitus position, the lesser curvature could be identified from both the ventral and dorsal sides.For the modified Hassab's operation, as in laparoscopic gastrectomy, many operators select the supine position for lesser curvature devascularization and gastric vessel ligation. However, after sufficient adhesion dissection around the stomach, anatomical structures can be identified in the right lateral decubitus position. For this approach, gravity is not an issue on the dorsal side, and the lesser curvature can be observed from both the ventral and dorsal sides with the patient in the right lateral decubitus position. Laparoscopically performing the modified Hassab's operation with the patient in the right lateral decubitus position is a feasible method.

Elderly patients who undergo major abdominal surgery are potentially at a higher risk of perioperative mortality and postoperative complications. Although laparoscopic surgery has been widely accepted as a less invasive surgical procedure for colorectal diseases, the benefits for elderly patients have not been validated. To compare postoperative outcomes and long-term survival between laparoscopic and open colorectal surgery in the elderly population. A literature search was electronically performed to identify all studies comparing postoperative outcomes between laparoscopic and open colorectal resections in the elderly population. Primary outcomes were postoperative mortality and complications, and the secondary outcome was long-term survival. Overall, 30 studies (70,946 patients) met our inclusion criteria. Laparoscopic surgery was significantly associated with a decreased risk of perioperative mortality [odds ratio (OR), 0.55; 95 % confidence interval (CI), 0.45–0.68; P

Although incisional hernia (IH) is a common complication of abdominal surgery, the incidence rate and risk factors are not well known. The objectives of this study are to determine the incidence rate of IH following colorectal cancer surgery and to describe the associated risk factors. Between 2005 and 2010, patients who underwent surgery to treat colorectal cancer were examined. The diagnosis of IH was performed by CT scan, and the visceral fat area (VFA) and subcutaneous fat area (SFA) at the level of the umbilicus were calculated using a 3D-image analysis system. Survival analysis was used to assess the incidence and risk factors of IH. A total of 626 patients (326 open, 300 laparoscopic) were included in this study, with median follow-up of 54 (range 2–97) months. Forty patients were diagnosed with postoperative IH, and the cumulative, 5-year incidence of IH was 7.3 %. Univariate analysis revealed that age, body mass index, waist circumference, hip circumference, open laparotomy, wound infection, VFA, and SFA were significantly associated with incidence of IH. Multivariate analysis revealed that age [hazard ratio (HR) 1.043 (1.005–1.083), p = 0.027], open laparotomy [HR 4.410 (1.018–19.095), p = 0.047], and SFA [HR 1.013 (1.004–1.022), p = 0.005] were significant risk factors for developing IH. Higher age and SFA, along with open surgery, are risk factors for developing IH.

Background: The Ataxia telangiectasia mutated (ATM) is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. Recently, ATM was reported to correlate with breast cancer metastasis by regulating phosphorylated Snail which was known as a marker of epithelial-mesenchymal transition (EMT), however, it remains unclear in colorectal cancer (CRC). In this study we attempted to clarify the impact of ATM on the mechanism of EMT in CRC. Methods: Potential ATM levels were evaluated in human CRC cells (HT29 and SW480) by qPCR and western blot analysis. Cells were induced EMT by treated with TGF-b, were confirmed by the change of EMT markers (i.e. N-cadherin, E-cadherin, Snail and twist). Next, ATM levels were down-regulated by siRNA and the impact on EMT were evaluated by EMT markers. Invasive potential was evaluated by scratch assay. Results: HT29 showed significantly higher levels of ATM comparing to SW480 (p = 0.042). N-cadherin (p = 0.065), Snail (p = 0.034) and twist (p = 0.052) were highly observed in HT-29, while similar level of E-cadherin in SW480 (p = 0.692). Scratch assay revealed that approximately 4 times high migration was observed in HT29. TGF-b induced EMT such as elevation of N-cadherin and Snail (E-cadherin was not affected), leading to promotion of cell migration in SW480. ATM was successfully 48.4% down-regulated (p = 0.001) in SW480, which resulted in reducing cell migration (p = 0.033). Conclusions: ATM might be a critical regulator of EMT in colorectal cancer invasion. Citation Format: Hidena Takahashi, Masashi Tsuruta, Hirotoshi Hasegawa, Koji Okabayashi, Ryo Seishima, Shimpei Matsui, Toru Yamada, Takayuki Kondo, Takehiro Shimada, Mutsuhito Matsuda, Masashi Yahagi, Yusuke Yoshikawa, Yusuke Asada, Kiyoaki Sugiura, Yoshiyuki Suzuki, Yuki Tajima, Junpei Nakadai, Yuko Kitagawa. Ataxia telangiectasia mutated relates to epithelial-mesenchymal transition in colorectal cancer. [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 5193. doi:10.1158/1538-7445.AM2015-5193

A 65-year-old man who had been treated for prostate cancer was noted to have an incidental large rectal tumour on surveillance pelvic MRI. He subsequently underwent a colonoscopy that revealed a penduculated tumour in the rectum. When the tumour was inspected closely (figure 1), a white mobile tubular body was noted on the surface of the tumour. It was strongly suspected to be an anisakis worm. After carefully grasping and removing the worm using biopsy forceps, it was found …

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 333 in stage III. The mean of NFS was 1.32±1.55, where the included patients were categorized into 77 HF and 876 non-HF. 5-year liver-specific disease-free survival rate in HF was significantly poorer than non-HF (HS 87.0% vs. non-HF 94.5%, log-rank p=0.009). Multivariate analysis demonstrated that HF significantly promoted liver-specific recurrence compared to non-HF (HR=2.16, 95% CI, 1.00 to 4.64; p=0.049). Conclusions: Hepatic fibrosis had a great impact on hepatic recurrence after curative surgical resection of CRCs. These findings indicated that HF might be a favorable microenvironment in developing colorectal liver metastasis. The evaluation of the degree of HF can be useful in selection of adjuvant chemotherapy and postoperative surveillance.

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: 6.85) cm2/ m2, respectively. Eighteen patients were classified into the MVL group. The patients in MVL group significantly responded to the chemotherapy (RR of MVL: 11.1% vs. RR of non-MVL: 49.3%, p < 0.01). There was no significant difference in terms of high grade adverse effect between MVL and non-MVL group. Patients in MVL group had a significant shorter median PFS (MVL: 5.5 [2.5 - 10.1] months vs. non-MVL: 12.8 (3.8-80.5) months, p < 0.01) and median OS (MVL: 13.9 [6.2-61.2] months vs. non-MVL: 29.3 (8.2-94.0) months, p < 0.01). Multivariate analysis demonstrated that patients with MVL had significantly worse prognostic factor (OS: HR 3.51 [1.99-6.21], p < 0.01 and PFS: HR 8.27 [2.91-23.5], p < 0.01. Conclusions: The findings of this study suggested that MVL after the induction of the first line chemotherapy could be a novel predictive factor for chemotherapy response and prognosis. Further investigation should be required to clarify the mechanistic background.

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-hematologic toxicity of chemotherapy including CPT-11. Results: The median NFS was -1.302 (range=-5.158 to 2.62). Multivariate analysis revealed that NFS was an independent negative predictive marker for RR (coef -0.373 (-0.712 to -0.035), p = 0.031), although no contribution of NFS was observed to PFS (coef 0.958(0.786|1.168), p=0.672). In terms of the adverse events, high value of NFS is an independent risk factor in hematological toxicity (coef 0.93 (0.20 to 1.65), p = 0.012), while not in non-hematological toxicity (coef 0.198 (-0.218|0.613), p=0.351). Conclusions: The pretreatment NFS might be a feasible for predicting response and hematological toxicity in first line chemotherapy including CPT-11 against colorectal cancer.

610 Background: In colorectal cancer (CRC), liver metastasis is one of the critical prognostic factors. However, its pathogenesis still remains unclear. “Stream line theory” is known to be in the liver, where the bloodstream from superior and inferior mesenteric vein make a laminar flow in portal vein, and pour into the right and left hepatic vein, respectively. Recently we have elucidated that stream line theory might affect the pattern of liver metastasis in CRC. We anticipated that the way how to administrate anticancer drug also influence on the effectiveness for liver metastasis in CRC, namely oral administrated drug is absorbed in small intestine and delivered to the right lobe in the liver mainly. We hypothesized that oral intake of anticancer drug suppressed especially recurrence in the right hepatic lobe. The aim of this study is to elucidate the specific pattern of recurrence after curative resection of CRC depending on the way to administrate anticancer drug as adjuvant chemotherapy (AC). Methods: Between January 2003 and September 2013, of 365 patients who were received AC following R0 excision of primary CRC in our institution, we analyzed 94 patients who were diagnosed recurrence. They were divided into 2 groups: 64 patients were received only oral anticancer drug as AC following curative resection of CRC (PO group), and the others are distributed into IV group. A comparative review of clinicohistopathological factors and recurrence pattern were statistically performed. Results: Preoperative CEA levels were significantly higher in IV group than PO group (3.3 vs. 7.6, p=0.03). No other difference was observed in background factor of 2 groups. Comparing the recurrence pattern, 11 (17.2%) were diagnosed recurrence in the right hepatic lobe in PO group while 11 (36.7%) in IV group. There was significantly lower incidence of recurrence in the right hepatic lobe in PO group comparing with IV group (HR=2.79, 95% CI=0.92 to 8.37; p=0.04). Conclusions: AC by oral anticancer drug might specifically suppressed recurrence in the right hepatic lobe behind “stream line theory” in which oral anticancer drug is absorbed in small intestine and mainly drained into the right hepatic lobe.