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It remains controversial whether the abdominoperineal resection (APR) procedure itself has a negative impact on prognosis compared with sphincter-saving surgery (SSS). The purpose of this study was to investigate whether the operation type affects the prognostic outcome in rectal cancer using a multicenter database in Japan. The study involved 2533 patients who underwent APR or SSS and were registered in the Japanese Society for Cancer of the Colon and Rectum database, which includes data from 74 centers, between 2003 and 2007. The primary endpoints were overall survival (OS) and relapse-free survival (RFS). The secondary endpoints were local recurrence rate (LRR) and pathological radial margin (pRM) status. Multivariate analysis identified pathological tumor depth, lymph node status, and pRM status to be associated with oncological outcomes (OS, RFS, LRR). Although the oncological outcomes were worse after APR than after SSS in univariate analysis, there was no significant difference in OS (hazard ratio 1.08; 95% confidence interval [CI] 0.85–1.37) or RFS (hazard ratio 1.06; 95% CI 0.87–1.30) between APR and SSS. There was also no significant difference in LRR (odds ratio 1.11, 95% CI 0.70–1.77). Multivariate analysis showed that operation type was associated with positive pRM (odds ratio 3.13, 95% CI 0.18–0.56). There was no significant difference in oncological outcomes between APR and SSS for rectal cancer. The risk of positive pRM was higher for APR and performing radial margin-negative surgery is an important factor in improving the oncological outcomes of APR. [ABSTRACT FROM AUTHOR]

Purpose: The incidence and time of onset of acute chemotherapy-induced peripheral neuropathy (ACIPN) caused by oxaliplatin remain unclarified. Hence, we investigated the prevalence, onset time, and location of ACIPN symptoms in patients with colorectal cancer (CRC) receiving oxaliplatin without cold stimulation. Methods: The study cohort comprised patients receiving oxaliplatin for CRC at our hospital between April 2017 and August 2018. Patients were instructed not to touch and/or drink cold things and were monitored for ACIPN symptoms in the hospital for 24 h after chemotherapy. ACIPN symptoms that appeared > 24 h after chemotherapy were recorded at the next visit. Symptom appearance time was defined as the duration from the administration of chemotherapy until the appearance of paresthesia classified as grade 1 using the Common Terminology Criteria for Adverse Events. Results: Forty-five patients received chemotherapy, comprising 23 men and 22 women, aged 67 years (29–88 years). The location of ACIPN was the fingers in 55.6% of cases, pharynx in 26.7%, perioral region in 24.4%, and feet in 6.7%. The average duration from oxaliplatin administration to symptom development was 182 min (range 62–443 min) for the fingers, 291 min (176–432 min) for the pharynx, 311 min (127–494 min) for the perioral region, and 297 min (234–355 min) for the feet. Pharyngeal symptoms were more common in patients older than 65 years than in those younger than 65 years. Conclusions: The incidence and time of the onset of ACIPN caused by oxaliplatin varies between the body and regions. [ABSTRACT FROM AUTHOR]

Capecitabine is selectively converted from 5′-DFUR to 5-fluorouracil (5-FU) in tumours by thymidine phosphorylase (TP). We investigated the addition of 5-nitrouracil (5-NU), a TP inhibitor, into blood samples for precise measurements of plasma 5-FU concentrations. The plasma concentration of 5-FU was measured after capecitabine administration. Two samples were obtained at 1 or 2 h after capecitabine administration and 5-NU was added to one of each pair. Samples were stored at room temperature or 4 °C and 5-FU concentrations were measured immediately or 1.5 or 3 h later. The mean plasma 5-FU concentration was significantly higher at room temperature than at 4 °C (p < 0.001). The 5-FU concentration was significantly increased in the absence of 5-NU than in the presence of 5-NU (p < 0.001). The 5-FU change in concentration was greater in the absence of 5-NU, and reached 190% of the maximum compared with baseline. A significant interaction was found between temperature and 5-NU conditions (p < 0.001). Differences between the presence or absence of 5-NU were greater at room temperature than under refrigerated conditions. 5-FU plasma concentrations after capecitabine administration varied with time, temperature, and the presence or absence of 5-NU. This indicates that plasma concentrations of 5-FU change dependent on storage conditions after blood collection. [ABSTRACT FROM AUTHOR]

Introduction Laparoscopic (Lap) surgery has not been established as a standard procedure for locally advanced colon cancers. Here, we evaluated the safety and feasibility of Lap multivisceral resection (MVR) for tumors that had invaded adjacent organs (T4b). Methods We performed retrospective analyses using a single institutional database. Eighty-four patients who underwent Lap or open MVR for surgical T4b primary colon cancers satisfied the inclusion criteria. Results Among the 84 patients, 48 underwent Lap MVR and 36 underwent open MVR. More patients in the open group were clinical T4b and were receiving neoadjuvant chemotherapy. Patients in the open group had worse performance status ( P = 0.037) and tumors of greater diameter. Lap completion was achieved in 42 cases (87.5%); the conversion rate was highest in cases involving the urinary tract (40.0%). Lap reconstruction of the bladder or ureter was extremely challenging, and therefore, adjacent organ reconstruction influenced Lap completion. Regarding perioperative outcomes, Lap was superior to open surgery in terms of intraoperative blood loss, morbidity, and postoperative hospital stay. Conversion was required in six cases; five were strategic conversions, and conversion was not associated with severe morbidity. The microscopic positive surgical margin rate was not higher in the Lap group than in the open group. Kaplan-Meier analyses of overall and disease-free survival were comparable between the groups. Cox regression analyses revealed that the operative approach did not have a significant adverse effect on long-term outcomes. Conclusion The Lap approach could be considered for surgical T4b cancers, except for urinary tract invasion cases that require complicated reconstruction. [ABSTRACT FROM AUTHOR]

Background: Although liver resection combined with preoperative chemotherapy is expected to improve outcomes of patients with resectable colorectal liver metastasis (CRLM), there is as yet insufficient clinical evidence supporting the efficacy of preoperative systemic chemotherapy. The aim of this phase II study was to assess the feasibility and efficacy of preoperative FOLFOX systemic chemotherapy for patients with initially resectable CRLM. Methods: A prospective multi-institutional phase II study was conducted to evaluate the feasibility and efficacy of preoperative chemotherapy for resectable CRLM (ClinicalTrials.gov identifier number NCT00594529). Patients were scheduled to receive 6 cycles of mFOLFOX6 therapy before liver surgery. The primary endpoint was the macroscopic curative resection rate. Results: A total of 30 patients were included in this study. Two patients who were diagnosed with hepatocellular and intrahepatic cholangiocellular carcinoma based on pathology were excluded from the analysis. More than half of the patients (57 %) had solitary liver metastasis. The completion rate of preoperative chemotherapy was 64.3 % and the response rate was 53.6 %. Two patients were unable to proceed to liver resections due to disease progression and severe postoperative complications following primary tumor resection. Macroscopic curative resection was obtained in 89.3 % of eligible patients. Postoperative mortality and severe complication (≥Gr. 3) rates were 0 and 11 %, respectively. The 3-year overall and progression-free survival rates were 81.9 and 47.4 %, respectively. Conclusion: Our phase II study demonstrated the feasibility of liver resection combined with preoperative mFOLFOX6 therapy in patients with initially resectable CRLM. Further study is warranted to address the oncological effects of preoperative chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Decreased blood perfusion is an important risk factor for postoperative anastomotic leakage (AL). Fluorescence imaging with indocyanine green (ICG) provides a real-time assessment of intestinal perfusion. This study evaluated the utility of ICG fluorescence imaging in determining the transection line of the proximal colon during laparoscopic colorectal surgery with double stapling technique (DST) anastomosis.Methods: This was a prospective single-institution study of 68 patients with left-sided colorectal cancers who underwent laparoscopic colorectal surgery between August 2013 and December 2014. After distal transection of the bowel, the specimen was extracted extracorporeally and then the mesentery was divided along the planned transection line determined by the surgeons' judgement under normal q. After ICG was injected intravenously, intestinal perfusion of the proximal colon was assessed in the fluorescent imaging mode. Intestinal perfusion was examined in relation to the patient-, tumor- and surgery-related variables using univariate and multivariate analyses.Results: ICG fluorescence imaging showed that intestinal perfusion was present at 3 mm (median) distal to the initially planned transection line. ICG fluorescence imaging resulted in a proximal change of the transection line by more than 5 mm in 18 patients (26.5 %) and, particularly, by more than 50 mm in 3 patients (4.4 %), compared with the initially planned transection line. Univariate analysis revealed that diabetes mellitus, anticoagulation therapy, preoperative chemotherapy and operative time were significantly associated with poor intestinal perfusion. Multivariate analysis identified anticoagulation therapy (P = 0.021) and preoperative chemotherapy (P = 0.019) as independent risk factors for poor intestinal perfusion. Three patients (4.5 %) with a change of transection line developed AL.Conclusions: ICG fluorescence imaging is useful for determining the transection line in laparoscopic colorectal surgery with DST anastomosis. Anticoagulation therapy and preoperative chemotherapy are important risk factors for poor intestinal perfusion. [ABSTRACT FROM AUTHOR]

TAS-102 significantly improves overall survival in patients with metastatic colorectal cancer. The most common adverse event of TAS-102 is bone marrow suppression, which leads to neutropenia. The incidence of neutropenia is high, and there is no known effective prevention method. Furthermore, the administration method of TAS-102 is complicated. We reported that neutropenia could be avoided by changing to a simple administration method of TAS-102. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the outcomes of patients with colorectal cancer and initially unresectable or not optimally resectable liver metastases, who were treated using the liver-first approach in the era of modern chemotherapy in Japan. Methods: We analyzed and compared data retrospectively on patients with asymptomatic resectable colorectal cancer and initially unresectable or not optimally resectable liver metastases, who were treated either using the liver-first approach ( n = 12, LF group) or the primary-first approach ( n = 13, PF group). Results: Both groups of patients completed their therapeutic plan and there was no mortality. Postoperative morbidity rates after primary resection and hepatectomy, and post-hepatectomy liver failure rate were comparable between the groups ( p = 1.00, p = 0.91, and p = 0.55, respectively). Recurrence rates, median recurrence-free survival since the last operation, and 3-year overall survival rates from diagnosis were also comparable between the LF and PF groups (58.3 vs. 61.5 %, p = 0.87; 10.5 vs. 18.6 months, p = 0.57; and 87.5 vs. 82.5 %, p = 0.46, respectively). Conclusions: The liver-first approach may be an appropriate treatment sequence without adversely affecting perioperative or survival outcomes for selected patients. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the effect of intraoperative blood loss (IBL) on short- and long-term outcomes of colorectal cancer surgery for very elderly patients. Methods: We acquired the data of consecutive patients aged 80 years or older who underwent elective radical surgery for stage I to III colorectal cancer between January 2003 and December 2007 in 41 institutions. The patients were divided into high and low IBL groups, and the differences in postoperative morbidity and survival between the two groups were primarily assessed. Eleven factors were treated as potential confounders in multivariate analyses. Results: A total of 1554 patients were eligible for this study, with an age range of 80-103 years. Median IBL was 71 ml (interquartile range, 25 to 200 ml), and 412 patients had IBL ≥200 ml. Morbidity was 46 % among patients with IBL ≥200 ml, compared with 30 % among those with IBL <200 ml ( p < 0.001). Patients with IBL ≥200 ml had worse overall survival rates and recurrence-free survival rates at 1, 3, and 5 years than those with IBL <200 ml. In multivariate analyses, IBL ≥200 ml was identified as an independent risk factor for postoperative adverse events (odds ratio (OR) 1.41, 95 % confidence interval (CI) 1.08 to 1.86), overall survival (hazard ratio (HR) 1.34, 95 % CI 1.04 to 1.72), and recurrence-free survival (HR 1.29, 95 % CI 1.03 to 1.62). Conclusion: The degree of IBL is significantly associated with postoperative morbidity and survival in very elderly colorectal cancer patients. [ABSTRACT FROM AUTHOR]

The article presents questions and answers related to gastroenterological surgery of large intestine including recommendation of laparoscopic surgery (LS) for colon cancer, previous diseases to be considered for LS and, suitability of LS for elderly patients.

A 79-year-old woman who had undergone laparoscopic radical cystectomy and ileal conduit construction for bladder cancer 4 years earlier presented to our hospital with anemia. We diagnosed advanced ascending colon cancer ( cT4bN2M1) and documented tumor regression after six courses of folinic acid, 5-fluorouracil, and oxaliplatin therapy. We then performed laparoscopic right hemicolectomy. Intraoperatively, we found that the right colic artery was the feeding artery of the tumor, whereas the ileocolic artery, which was the main feeder of the conduit, was not. We performed lymph node dissection along the surgical trunk with central vascular ligation of the right colic artery and the right branch of the middle colic artery while preserving the ileal conduit and its blood supply (ileocolic artery and ileal branches). The postoperative course was uneventful, and the patient remains well and cancer-free 2 years after colonic surgery. We believe that this is the first report of laparoscopic right colectomy in a patient with an ileal conduit. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the second most common cancer, and is the third leading cause of cancer-related death in Japan. The majority of these deaths is attributable to liver metastasis. Recent studies have provided increasing evidence that the chemokine-chemokine receptor system is a potential mechanism of tumor metastasis via multiple complementary actions: (a) by promoting cancer cell migration, invasion, survival and angiogenesis; and (b) by recruiting distal stromal cells (i.e., myeloid bone marrow-derived cells) to indirectly facilitate tumor invasion and metastasis. Here, we discuss recent preclinical and clinical data supporting the view that chemokine pathways are potential therapeutic targets for liver metastasis of colorectal cancer. [ABSTRACT FROM AUTHOR]

We previously performed gene expression profile analyses of 20 intestinal-type gastric cancers, and identified a set of genes whose expression levels were elevated in cancer tissues compared to their corresponding non-cancerous tissues. In the present study we focused on the immunoglobulin superfamily 11 gene (IGSF11). Its expression was also elevated in colorectal cancers and hepatocellular carcinomas as well as intestinal-type gastric cancers. Northern blot analysis showed that it was expressed abundantly in testis and ovary. These data suggest that IGSF11 is a good candidate of cancer-testis antigen. Furthermore, suppression of IGSF11 by siRNA retarded the growth of gastric cancer cells. To investigate the possibility of clinical application of peptide vaccine to IGSF11, we synthesized candidate epitope peptides for IGSF11 and tested whether the peptides elicit IGSF11-specific CTL. As a result, we successfully established oligo-clonal CTL by stimulation with IGSF11-9-207 (ALSSGLYQC). In addition, we also established additional CTL using IGSF11-9V (ALSSGLYQV), anchor-modified peptides of IGSF11-9-207. These peptides showed IGSF11-specific cytotoxic activity in an HLA-A*0201-restricted fashion, suggesting that these peptides may be applicable for cancer immunotherapy. These findings have provided a novel insight into carcinogenesis of the stomach, colon and liver, and will be helpful for the development of novel therapeutic strategies to a wide range of human cancers. ( Cancer Sci 2005; 96: 498 –506) [ABSTRACT FROM AUTHOR]

This phase 2 study evaluated the safety and efficacy of perioperative chemotherapy with S-1 plus oxaliplatin (SOX) for stage III colorectal cancer (CRC). Patients with stage III CRC received surgery after neoadjuvant chemotherapy (NAC; SOX 4 cycles) and adjuvant chemotherapy (AC; SOX 4 cycles). The primary endpoints were response rate and safety. We enrolled 30 patients. Their median age was 62 years (range: 43–87 years); 53% were women. They received a median of 4 cycles (range: 1–4) of NAC and a median 4 cycles (range: 0–4) of AC. Five patients interrupted NAC treatment because of toxicity (grade 3 diarrhoea [n = 1], grade 3 ileus [n = 1], and grade 3–4 thrombocytopenia [n = 3]). Patients' responses were complete responses: n = 2 (6.6%), partial responses: n = 21 (70%), stable disease: n = 6 (20.0%), and progressive disease: n = 1 (3.3%; response rate: 73.3%). Curative resection was performed in 29 patients. No patients showed anastomotic leakage. Five-year overall survival and disease-free survival were 83.3% and 76.7%, respectively (median follow-up time: 48 months). NAC using SOX regimen is safe and effective, and may lead to reduced local recurrence and distant metastasis. Long-term outcomes are awaited to evaluate further the efficacy of this strategy (UMIN000006790). [ABSTRACT FROM AUTHOR]

Background & Aims: Loss of the tumor suppressor SMAD4 correlates with progression of colorectal cancer (CRC). In mice, colon tumors that express CCL9 recruit CCR1+ myeloid cells, which facilitate tumor invasion and metastasis by secreting matrix metalloproteinase 9. Methods: We used human CRC cell lines to investigate the ability of SMAD4 to regulate expression of CCL15, a human ortholog of mouse CCL9. We used immunohistochemistry to compare levels of CCL15 and other proteins in 141 samples of human liver metastases. Results: In human CRC cell lines, knockdown of SMAD4 increased CCL15 expression, and overexpression of SMAD4 decreased it. SMAD4 bound directly to the promoter region of the CCL15 gene to negatively regulate its expression; transforming growth factor-β increased binding of SMAD4 to the CCL15 promoter and transcriptional repression. In livers of nude mice, SMAD4-deficient human CRC cells up-regulated CCL15 to recruit CCR1+ cells and promote metastasis. In human tumor samples, there was a strong inverse correlation between levels of CCL15 and SMAD4; metastases that expressed CCL15 contained 3-fold more CCR1+ cells than those without CCL15. Patients with CCL15-expressing metastases had significantly shorter times of disease-free survival than those with CCL15-negative metastases. CCR1+ cells in the metastases expressed the myeloid cell markers CD11b and myeloperoxidase, and also matrix metalloproteinase 9. Conclusions: In human CRC cells, loss of SMAD4 leads to up-regulation of CCL15 expression. Human liver metastases that express CCL15 contain higher numbers CCR1+ cells; patients with these metastases have shorter times of disease-free survival. Reagents designed to block CCL15 recruitment of CCR1+ cells could prevent metastasis of CRC to liver. [Copyright &y& Elsevier]

Background: Lymph node metastasis is one of the most critical prognostic factors in patients with colorectal cancer. Although regional lymph nodes should be surgically resected and pathologically examined, techniques for the intraoperative diagnosis of lymph node metastasis remain to be well established. Fluorescence diagnosis using 5-aminolevulinic acid (5-ALA) is a promising technique for evaluating various malignancies. After exogenous administration of 5-ALA, protoporphyrin IX (PPIX) accumulates in malignant cells and can be detected as red fluorescence. In this study, we investigated the usefulness of fluorescence diagnosis using 5-ALA for the detection of lymph node metastasis in a mouse model of colon cancer. Materials and Methods: An orthotopic colon cancer model was prepared by inoculating the cecal wall of nude mice with HCA7, a human colon adenocarcinoma cell line. After 3 wk, 40 mg/kg of 5-ALA was administered intraperitoneally (IP) or orally (PO). Fluorescence diagnosis with a D-Light System (Karl Storz) was then performed after 3 or 6 h. Results: In the IP group, PPIX fluorescence was detected in metastatic lymph nodes as well as in other malignant lesions, including primary tumors and abdominal implantations, while non-metastatic nodes were fluorescence-negative. In contrast, no obvious fluorescence was detected in cancerous tissues in the PO group. Conclusions: PPIX fluorescence induced by intraperitoneal injection of 5-ALA allows metastatic lymph nodes to be accurately diagnosed in this mouse model. This technique may facilitate the intraoperative diagnosis of lymph node metastases from colon cancer in a clinical setting. [ABSTRACT FROM AUTHOR]