This study compared the effectiveness of 1-day vs 3-days antibiotic regimen to prevent surgical site infection (SSI) in open liver resection. We performed a randomized controlled non-inferiority trial in 480 patients at 39 hospitals across Japan (registered as UMIN000002852). Patients with hepatocellular carcinoma scheduled to undergo resection were randomly assigned to receive either a 1-day regimen for antimicrobial prophylaxis, or a 3-day regimen. The primary endpoint was the incidence of SSI. Among 480 randomized patients, 232 assigned to the 1-day regimen and 235 to the 3-day regimen were included in the full analysis set. Baseline characteristics of the two groups were well balanced. SSI was diagnosed in 22 patients (9.5%) in the 1-day group vs 23 patients (9.8%) in the 3-day group (difference, – 0.30; 90% CI – 4.80 to 4.19% [95% CI – 5.66% to 5.05%]; one-sided P = 0.001 for non-inferiority), meeting the non-inferiority hypothesis. In both groups, remote site infection (16 [6.9%] vs 22 [9.4%], P ˂ 0.001 for non-inferiority) and drain-related infection (5 [2.2%] vs 4 [1.7%], P ˂ 0.001 for non-inferiority) were comparable. To prevent SSI in liver cancer surgery, a 1-day regimen of flomoxef sodium is recommended for antimicrobial prophylaxis because of confirming the non-inferiority to longer usage.

Background: The SACURA trial is a phase III study to evaluate the superiority of 1-year adjuvant treatment with oral tegafur-uracil (UFT) to surgery alone in stage II colon cancer, in which survival benefit of 1-year UFT was not demonstrated (Eur J Cancer 96:54-63, 2018). In an additional biomarker study, we studied MSI status and 18qLOH of cancer tissues and evaluated their clinical value in stage II colon cancer patients. Methods: A total of 1026 samples were collected from patients enrolled in the SACURA trial. MSI was evaluated by 5 markers; BAT25, BAT26, D2S123, D5S346, and D17S250. MSI-high (MSI-H) was defined as the presence of instability in more than 20% of the markers. 18qLOH was evaluated by 3 markers; D18S69, D18S74E, and D18S851. 18qLOH positivity was defined as the presence of LOH in any of the 18q markers. 18q LOH negativity was strictly defined as the presence of at least one informative markers and the absence of LOH. Results: MSI-H was observed in 74 (7.2%) patients. The 18q LOH was present in 526 patients (51.3%) and LOH negativity was observed in 354 (34.5%). Informative LOH data was not available in 146 patients (14.2%). Relapse free survival (RFS) in MSI-H patients was better than that in non MSI-H (HR: 0.40, 95%CI: 0.17-0.98, p = 0.045). RFS in 18qLOH positive patients was significantly worse than in 18qLOH negative patients (hazard ratio: 1.44, 95%CI: 1.01-2.07, p = 0.047). When the patients were divided into 3 groups using MSI status and 18qLOH, approximately 5% differences of RFS were observed among the subgroups (Table). In the group 1 and 2, 5-year RFS rates were favorable and there were no differences in RFS between the treatment arms. In the group 3, 5-year RFS rate in the UFT group was +3% better than in the surgery-alone group although the difference was not significant.Table: 520P5yRFS in the subgroups divided by MSI status and 18qLOHSubgroup divided by MSI status and 18qLOH5yRFSOverallSurgery- alone groupUFT groupgroup 1: MSI-H92.9% (N = 74)94.3% (N = 36)91.7% (N = 38)group 2: non MSI-H and 18qLOH negative87.2% (N = 327)87.5% (N = 153)87.0% (N = 174)group 3: non MSI-H and 18qLOH positive/non- informative82.5% (N = 625)81.0% (N = 320)84.0% (N = 305) Open table in a new tab Conclusions: In stage II colon cancer, adjuvant chemotherapy might be unnecessary for MSI-H or 18qLOH negative patients. MSI status and 18qLOH might be useful biomarkers in stage II colon cancers. Clinical trial identification: NCT00392899. Legal entity responsible for the study: Sacura Study Group. Funding: The Foundation for Biomedical Research and Innovation, Translational Research Informatics Center (TRI), under the funding contract with Taiho Pharmaceutical Co. Ltd. Disclosure: T. Ishikawa: Honoraria: Chugai Pharma, Merck Serono, Takeda, Sanofi, Taiho Pharmaceutical; Research funding: Taiho Pharmaceutical. M. Ishiguro: Honoraria: Chugai Pharma, Merck Serono, Takeda, Sanofi, Taiho Pharmaceutical; Advisory role: Taiho Pharmaceutical; Research funding: Yakult, Taiho Pharmaceutical. H. Ueno: Honoraria: Chugai Pharma, Yakult, Eazai, Taiho Pharmaceutical. H. Uetake: Honoraria: Chugai Pharma, Merck Serono, Takeda, Taiho Pharmaceutical; Advisory role: Sanofi; Research funding: Taiho Pharmaceutical. N. Tomita: Research funding: Chugai Pharma, Taiho Pharmaceutical. Y. Shimada: Honoraria: Chugai Pharma, Yakult, Takeda, Lilly, Taiho Pharmaceutical; Research funding Merk Serono, Lilly, MSD, Taiho Pharmaceutical. K. Kotake: Honoraria: Chugai Pharma, Bristol-Myers Squibb, Taiho Pharmaceutical. M. Watanabe: Honoraria: Taiho Pharmaceutical: Research funding: Taiho Pharmaceutical: Travel and accommodations: Taiho Pharmaceutical. H. Mochizuki: Honoraria: Becton, Dickinson and Company, Taiho Pharmaceutical; Advisory role: Otsuka Pharmaceutical. K. Sugihara: Honoraria: Chugai Pharma, Lilly, Novertis, Bayer, Taiho Pharmaceutical; Advisory role: Otsuka Pharmaceutical; Research funding: Chugai Pharma, Takeda, Taiho Pharmaceutical. All other authors have declared no conflicts of interest.

Background: Efficacy of adjuvant chemotherapy in patients with stage II colon cancer is still controversial. The SACURA trial is a randomised-controlled study evaluating the superiority of 1-year adjuvant treatment with oral tegafur-uracil (UFT) to surgery alone for stage II colon cancer. Methods: Patients were randomly assigned to the surgery-alone group or UFT group (UFT at 500-600 mg/day for 5 days, followed by 2-day rest, for 1 year). The primary end-point was disease-free survival (DFS). Target sample size was 2000, determined with one-sided alpha of 0.05, power of 0.9 and assumed hazard ratio (HR) 0.729. Results: A total of 1982 patients (997 in the surgery-alone group and 985 in the UFT group) were analysed. Median follow-up was 69.5 months, median age was 66 years and for stage IIA/IIB/IIC, the distribution was 84%/13%/3%. The 5-year DFS rate was 78.4% in the surgery-alone group and 80.2% in the UFT group. The HR for DFS was 0.91 (95% confidence interval [CI], 0.75-1.10; pZ0.31); superiority of UFT was not demonstrated. Approximately 9% of patients experienced second cancers, which consist 40.7% of the DFS events. The 5-year relapse-free and overall survival rates of the surgery-alone and UFT group were 84.6% and 87.2% (HR, 0.82; 95% CI, 0.65-1.04) and 94.3% and 94.5% (HR, 0.93; 95% CI, 0.66-1.31), respectively. Subgroup analysis failed to disclose superiority in prognosis of adding UFT to the patients with risk factors for recurrence. Conclusions: Superiority of 1-year adjuvant UFT over surgery alone was not demonstrated in stage II colon cancer. Patients with risk factors for recurrence did not benefit from UFT. Trial registration: ClinicalTrials. Gov. #NCT00392899. (C) 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

BACKGROUND:Open total gastrectomy carries a high risk of surgical-site infection (SSI). This study evaluated the non-inferiority of antimicrobial prophylaxis for 24 compared with 72 h after open total gastrectomy.METHODS:An open-label, randomized, non-inferiority study was conducted at 57 institutions in Japan. Eligible patients were those who underwent open total gastrectomy for gastric cancer. Patients were assigned randomly to continued use of β-lactamase inhibitor for either 24 or 72 h after surgery. The primary endpoint was the incidence of SSI, with non-inferiority based on a margin of 9 percentage points and a 90 per cent c.i. The secondary endpoint was the incidence of remote infection.RESULTS:A total of 464 patients (24 h prophylaxis, 228; 72 h prophylaxis, 236) were analysed. SSI occurred in 20 patients (8·8 per cent) in the 24-h prophylaxis group and 26 (11·0 per cent) in the 72-h group (absolute difference -2·2 (90 per cent c.i. -6·8 to 2·4) per cent; P < 0·001 for non-inferiority). However, the incidence of remote infection was significantly higher in the 24-h prophylaxis group.CONCLUSION:Antimicrobial prophylaxis for 24 h after total gastrectomy is not inferior to 72 h prophylaxis for prevention of SSI. Shortened antimicrobial prophylaxis might increase the incidence of remote infection. Registration number: UMIN000001062 ( http://www.umin.ac.jp).

3611 Background: Efficacy of adjuvant chemotherapy for stage II colon cancer is still controversial. We conducted the SACURA trial, a phase III study which evaluated the superiority of 1-year adjuvant treatment with oral tegafur-uracil (UFT) to surgery alone in stage II colon cancer. However, survival benefit of 1-year UFT to surgery alone was not demonstrated (ASCO2016 abst#3617). We herein aimed to identify risk factors for recurrence in the stage II patients “without adjuvant chemotherapy”, and to stratify the prognosis by using these factors. Methods: Among a total of 982 patients without adjuvant chemotherapy enrolled to the SACURA trial, we extracted the factors correlated to recurrence using a univariate and multivariate Cox proportional hazard model. 943 and 935 patients in the surgery alone group and UFT group were divided to subgroups according to the number of risk factors, and the recurrence rate in each subgroup was evaluated. Results: Among the conventional clinicopathological characteristics, the multivariate analysis identified pT4, elevated CEA, and examined lymph nodes less than 12 as significant risk factors for recurrence. The rate of patients with 0, 1, 2, and 3 risk factors were 45.0%, 42.4%, 11.5%, and 1.1%, respectively. The recurrence rate for each subgroup was shown in the table: the recurrence rate increased with number of risk factors, while 10.2% of patients without any risk factors developed recurrence. Difference in the recurrence rate between the treatment groups was significant in patients without risk factor, marginal in patients with 1 risk factor, and none in patients with >1 factors. Conclusions: pT4, elevated CEA, and examined lymph nodes less than 12 were identified as risk factors for recurrence in stage II colon cancer patients. The recurrence rate was divided by the number of these risk factors, but we could not extract the very-low risk group in whom adjuvant therapy is unnecessary. Induction of novel risk factors other than conventional clinicopathological characteristics is recommended. Clinical trial information: NCT00392899. [Table: see text]

3609 Background: Growing number of studies indicate tumor budding is a significant prognostic factor in colorectal cancer (van Wyk, et al. Cancer Treat Rev 2015), but this has been shown only in retrospective studies. We prospectively evaluated prognostic factors in stage II colon cancer to determine their prognostic value in a multi-institutional phase III study (SACURA trial, ASCO2016 abst#3617). Methods: A total of 991 patients with curatively resected stage II colon cancer (2006–2010; 136 institutions) were included in the study. Tumor budding was defined as an isolated cancer cell or a cluster composed of fewer than five cells in the invasive frontal region, and was graded based on its number within a microscopic field of a 20x objective lens (0.785 mm2) in the hotspot. Tumors with < 5, 5–9, and ≥10 budding foci were classified as grades G1, G2, and G3, respectively. All clinical and pathological data including the grade of budding were prospectively recorded and prognostic analyses were performed at 5 years after the completion of registration. Results: According to budding grading, 376, 331 and 284 tumors were classified as G1, G2, and G3, and 5-year relapse-free survival (RFS) rate was 90.9%, 85.1%, and 74.4%, respectively ( P < 0.0001). Budding grade was significantly associated with the incidence of recurrence in the liver, lung, lymph node, and peritoneum ( P < 0.0001–0.01). Among conventional factors, T stage and the serum CEA levels were associated with RFS, however, tumor grade, lymphatic and venous invasions, and the number of lymph node examined were not significant factors. Multivariate analysis for RFS showed budding, along with T stage, exerted an independent influence on prognostic outcome. Budding grade surpassed T stage and tumor grade in the ability to stratify patients by RFS (Harrell’s c-index, 0.63, 0.59, and 0.54, respectively). Conclusions: Our prospective study indicates that the grade of tumor budding is more informative for prognostic prediction than conventional prognostic factors in stage II colon cancer. The role of this prognostic factor should be highlighted in the adjuvant treatment setting, and conversely, some of prognostic factors adopted in clinical guidelines may need to be reconsidered. Clinical trial information: NCT00392899.

e15155 Background: The SACURA trial is a phase III study to evaluate the superiority of 1-year adjuvant treatment with oral tegafur-uracil (UFT) to surgery alone for stage II colon cancer. Superiority of adjuvant treatment with UFT to surgery alone was not demonstrated (ASCO2016 abst#3617). In an additional translational study, we assessed microsatellite instability (MSI) status of cancer tissues and prospectively examined the association of MSI with prognosis in stage II colon cancer patients. Methods: Formalin-fixed, paraffin-embedded samples were prospectively collected from 1026 patients enrolled in the SACURA trial. MSI was evaluated using 5 markers; BAT25, BAT26, D2S123, D5S346, and D17S250. MSI-high (MSI-H) was defined as the presence of instability in more than 20% of the markers. Median follow-up time was 69.6 months. Results: MSI-H, MSI-low (MSI-L) and microsatellite-stable (MSS) was observed in 74 (7.2%), 24 (2.3%), and 928 (90.5%) samples, respectively. Patients with MSI-H was significantly frequent in female, right-sided colon cancers, > 5cm tumors, poor histological type, and elevated CEA. Relapse rate for MSI-H patients (4.1%) was significantly lower than that for MSI-L/MSS cancer (13.4%, p = 0.02). Relapse free survival (RFS) in MSI-H patients was significantly better than in MSI-L/MSS patients (hazard ratio: 0.40, 95%CI: 0.17-0.98, p = 0.045), as well as adjusted results by prognostic factors. The 5-year RFS rates in MSI-H and MSI-L/MSS patients were 92.9% and 84.1%, respectively. Although there was no statistical significance, the 5-year RFS rate in MSI-H patients was tended to be better than that in MSI-L/MSS patients in the surgery alone group (94.3% vs. 83.1%, p = 0.086) as well as in the UFT group (91.7% vs. 85.1%, p = 0.233). Conclusions: MSI was an independent prognostic factor in stage II colon cancers. By considering their favorable RFS, adjuvant chemotherapy for stage II colon cancer patients with MSI-H may be unnecessary. Clinical trial information: NCT00392899.

3617 Background: Efficacy of adjuvant chemotherapy in stage II colon cancer patients is still controversial. The SACURA trial is a phase III study to evaluate the superiority of 1-year adjuvant treatment with oral tegafur-uracil (UFT) to surgery alone for stage II colon cancer in a large population. Methods: 20-80 aged patients with curatively resected stage II colon cancer were randomly assigned to the surgery alone group or UFT group (UFT at 500-600 mg/day as tegafur in 2 divided doses for 5 days, followed by 2-day rest, then repeated for 1 year). Primary endpoint was disease-free survival (DFS), and the secondary endpoints were overall survival (OS), recurrence-free survival (RFS), and safety. Sample size was 2000 determined with an assumed hazard ratio (HR) 0.729, respectively, a two-sided significance level of 5%, and a power of 90%. Results: A total of 1982 patients (997 in the surgery alone group and 985 in the UFT group) were included in the efficacy analysis. Median follow-up was 69.5 months, the median age at enrollment was 66 years, and stage IIA/IIB/IIC were 84%/13%/3%, respectively. The 5-year DFS rate was 78.4% in the surgery alone group and 80.2% in the UFT group. The HR for DFS was 0.91 (95%CI, 0.75-1.10; p = 0.307), and superiority of the UFT group was not demonstrated. Approximately 9% of patients in the both groups experienced second cancers, which consist 41.7% of the DFS events. The 5-year RFS rate was 84.6% and 87.2% (HR, 0.82; 95%CI, 0.65-1.04), and the 5-year OS rate was 94.3% and 94.5% (HR, 0.93; 95%CI, 0.66-1.31) in the surgery alone group and the UFT group, respectively. The completion rate of the 1-year UFT was 60.8%. The Incidence of grade 3/4 adverse events in the UFT group was 3.7% for ALT elevation, 3.3% for AST elevation, 1.4% for hyperbilirubinemia, 2.6% for anorexia, 1.9% for nausea, 1.4% for diarrhea, and < 1% for hematologic toxicities. Conclusions: Superiority of 1-year adjuvant treatment with UFT to surgery alone was not demonstrated in patients with stage II colon cancer. Clinical trial information: NCT00392899.

3570 Background: The ACTS-CC trial, a randomized phase III trial, demonstrated that adjuvant therapy with S-1 for stage III colon cancer was non-inferior in 3-year disease-free survival (DFS) to that of tegafur-uracil plus leucovorin (UFT/LV). We updated DFS and overall survival (OS), and performed some clinically relevant subgroup analyses. Methods: A total of 1,535 patients with stage III colon cancer were randomly assigned to receive S-1 (80-120 mg/day on days 1-28 every 42 days, 4 courses) or UFT/LV (UFT: 300- 600 mg/day and LV: 75 mg/day on days 1-28 every 35 days, 5 courses). Primary endpoint was DFS. Secondary endpoints were OS and safety. Results: A total of 1518 patients (758 in the S-1 group and 760 in the UFT/LV group) were included in the efficacy analysis. Median follow-up was 63.5 months, the mean age at enrollment was 64.5 years, wide lymph node dissection (D3) was done in 79.8%, the median number of dissected lymph nodes was 17, and stage IIIA/IIIB/IIIC were 15%/71%/14%. The hazard ratio (HR) for DFS was 0.88 (95%CI, 0.74-1.06; p = 0.177). The 5-year DFS rate was 70.2% in the S-1 group and 66.9% in the UFT/LV group. In the subgroup analysis, no significant interactions were identified between the major baseline characteristics and the DFS in S-1 and UFT/LV, except for histological type; favors S-1 in patients with poorly-differentiated adenocarcinoma. Approximately 5% of patients in the both groups experienced second cancers. Among the patients with recurrences in each group, 46.3% and 44.7% underwent surgical resection as an initial treatment for recurrence. The HR for OS was 0.92 (95%CI, 0.72-1.17; p = 0.488). The 5-year OS rates were 86.0% and 84.4% in the S-1 and UFT/LV group, respectively. Conclusions: Adjuvant therapy of S-1 for stage III colon cancer was confirmed to be non-inferior both in DFS and OS to those of UFT/LV after long follow-up. Favorable OS might be brought by the high resection rate of recurrent lesions. Clinical trial information: NCT00660894.

従来の肛門吻合（CAA）やIntersphincteric resection（ISR）の発達により，外科的肛門管に及ぶ直腸癌でも肛門温存の可能な症例が増加している．しかし現時点で行われているISRにおいて，この手術法に対する考え方の混乱も見受けられる．腹腔側よりIntersphincteric planeを確認し，器械吻合を行った症例もISRとされていることも1つの理由である．現在のISRに対する認識は，SchiesselやRullierらが提唱するように経腹経肛門操作によるintersphincteric plane内での直腸剥離とDentate lineを指標としてその直上や肛門側の解剖学的肛門管で直腸と内肛門括約筋をen blocに切除し，CAAにより再建する手術法である．これは本学会の用語委員会において統一の見解とされ，（経腹経肛門的）括約筋間直腸切除術と呼ぶことで一致した．本手術法ではある程度の多彩な排便障害を伴うが，最近の長期観察の報告では腫瘍学的予後および排便機能，QOLは許容範囲内とされている．

The OSNA assay was able to detect lymph node metastases in gastric cancer patients in the clinical setting, and is a 17 useful tool for the intraoperative diagnosis of LN metastasis.

More than 85% of patients with T1 colorectal cancer have no lymph node metastasis and can be cured by endoscopic resection. To avoid unnecessary surgery after complete endoscopic resection, accurate histologic methods for evaluating resected specimens are needed to discriminate those at high risk for lymph node metastasis. A retrospective multi-institutional, cross-sectional study of 806 T1 colorectal cancer patients was conducted. A budding/sprouting score was incorporated for predicting lymph node metastasis in addition to other parameters, including the depth of submucosal invasion, histologic grade, and lymphovascular invasion. Lymph node metastasis was detected in 97 patients. Independent predictors of lymph node metastasis by multivariate analysis were depth of submucosal invasion ≥1000 μm (odds ratio (95% confidence interval)=5.56 (2.14–19.10)) and high-grade budding/sprouting (3.14 (1.91–5.21)). Among lesions with a depth of submucosal invasion ≥1000 μm, lymph node metastasis was detected in 59 (29%) of 207 patients with high-grade budding/sprouting, and in 34 (9%) of 396 with low-grade budding/sprouting. Lymph node metastasis was detected in only 4 (2%) of 203 lesions with a depth of submucosal invasion <1000 μm. Of these four tumors, three invaded lymphatic and/or venous vessels. Thus, the risk for lymph node metastasis can be classified into three groups: high risk with a depth of submucosal invasion ≥1000 μm and high-grade budding/sprouting, intermediate-risk with a depth of submucosal invasion ≥1000 μm and low-grade budding/sprouting, and low-risk with a depth of submucosal invasion <1000 μm. These findings revealed that a depth of submucosal invasion ≥1000 μm and high-grade budding/sprouting are powerful predictive parameters for lymph node metastasis in T1 colorectal cancer. This three-tier risk classification system will facilitate the decision for additional major surgery for T1 colorectal cancer patients after successful endoscopic treatment.

Surgical injury not only induces a systemic endocrine-metabolic response but also influences the function of the leukocytes and endothelial cells leading to various systemic responses. These responses appear to depend on the severity of surgical stress, which differs according to the surgical procedures. In this study, we investigated the response of monocytes and endothelial cells, and the development of systemic inflammatory response syndrome (SIRS) in relation to the severity of surgical stress. The postoperative clinical course was evaluated between patients undergoing an esophagectomy (ER group) and a distal gastrectomy (DG group). The tumor necrosis factor α (TNFα) production of monocytes, the serum interleukin 6 (IL-6) levels, the CD11b expression on either monocytes or granulocytes, and the intercellular adhesion molecule-1 (ICAM-1) expression on human umbilical vein endothelial cells (HUVECs) stimulated with culture supernatants of monocytes were compared between the 2 groups. The development of SIRS was observed in all patients in the ER group, whereas no patients demonstrated SIRS in the DG group. The serum IL-6 levels, TNFα production of monocytes, and CD11b intensity on monocytes or granulocytes in the ER group were higher than those in the DG group. In the ER group, the ICAM-1 intensity on HUVECs with monocytes immediately after operation significantly increased compared with before the operation. In conclusion, both the CD11b expression on monocytes and the TNFα production of monocytes are considered to reflect the degree of surgical stress, and the activation of endothelial cells stimulated with these activated leukocytes may therefore lead to both tissue and organ injury.

BACKGROUND S-1 is an oral fluoropyrimidine whose antitumor effects have been demonstrated in treating various gastrointestinal cancers, including metastatic colon cancer, when administered as monotherapy or in combination chemotherapy. We conducted a randomized phase III study investigating the efficacy of S-1 as adjuvant chemotherapy for colon cancer by evaluating its noninferiority to tegafur-uracil plus leucovorin (UFT/LV). PATIENTS AND METHODS Patients aged 20-80 years with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80-120mg/day on days 1-28 every 42 days; four courses) or UFT/LV (UFT: 300-600mg/day and LV: 75mg/day on days 1-28 every 35 days; five courses). The primary end point was disease-free survival (DFS) at 3 years. RESULTS A total of 1518 patients (758 and 760 in the S-1 and UFT/LV group, respectively) were included in the full analysis set. The 3-year DFS rate was 75.5% and 72.5% in the S-1 and UFT/LV group, respectively. The stratified hazard ratio for DFS in the S-1 group compared with the UFT/LV group was 0.85 (95% confidence interval: 0.70-1.03), demonstrating the noninferiority of S-1 (noninferiority stratified log-rank test, P < 0.001). In the subgroup analysis, no significant interactions were identified between the major baseline characteristics and the treatment groups. CONCLUSION Adjuvant chemotherapy using S-1 for stage III colon cancer was confirmed to be noninferior in DFS compared with UFT/LV. S-1 could be a new treatment option as adjuvant chemotherapy for colon cancer. CLINICALTRIALS.GOV: NCT00660894.

The oncogenic single nucleotide polymorphism rs6983267, located on 8q24.21, may affect copy number aberrations and/or expression profiles in colorectal cancer (CRC). We investigated the role of this single nucleotide polymorphism in the clinical outcome of CRC.

The accurate diagnosis of lymph node (LN) metastasis is important for making treatment decisions for gastric cancer patients. This multicenter study evaluated the clinical performance of the one-step nucleic acid amplification (OSNA) assay (Sysmex Corp.), an automated system that detects cytokeratin 19 (CK19) mRNA, in detecting LN metastases in gastric cancer patients.

Periodic paralysis is a group of heterogeneous disorders caused by mutations of several ion channel genes including sodium, calcium and potassium channels. Andersen–Tawil syndrome (ATS) is a form of periodic paralysis, characterized by a triad of periodic muscle weakness, cardiac arrhythmia and dysmorphic features. KCNJ2 gene, which encodes Kir2.1 subunit and forms inward rectifying potassium channel (IRK), is known to be responsible for ATS but only about 60% of the ATS patients harbor KCNJ2 mutations suggesting other causative genes. We employed an exome capture resequencing analysis to identify a genetic cause of ATS patient with no mutations in KCNJ2 . The proband was from a family with dominantly inherited arrhythmia, and exhibited episodic muscle weakness with reduced serum potassium concentration and prominent U waves on ECG. Exome capture resequencing analysis, which was restricted to 162 ion channels and related genes, revealed a mutation of KCNJ5 encoding Kir3.4 subunit. In heart, Kir3.4 assembles with Kir3.1 to form G-protein-activated inward rectifying potassium (GIRK) channel, which is predominantly expressed in atria and contributes regulation of heart rate by acetylcholine, but the function of GIRK channels in skeletal muscle has not been well-elucidated. Immunoblot revealed significant expression of Kir3.4 protein in human skeletal muscle. We suspected the possibility of heteromerical assembly of Kir3.4 with Kir2.1 in skeletal muscle. The functional consequences of the mutation were investigated using the channels heterologously expressed in Xenopus oocytes. When Kir2.1 was expressed with mutant Kir3.4, the inward rectifying current was significantly smaller compared to that with WT Kir3.4. There is no direct evidence for the heteromerization of Kir3.4 with Kir2.1 subunit in native tissue but the dominant negative effect of mutant Kir3.4 on IRK may well explain the clinical presentation of both skeletal and heart muscles.

3518 Background: The ACTS-CC trial is a phase III trial designed to validate non-inferiority of S-1 to UFT/LV, a standard treatment in Japan as adjuvant chemotherapy for stage III colon cancer. This is the first report which evaluated the efficacy of S-1 as adjuvant therapy for colon cancer. Methods: 20-80 aged patients with stage III colon cancer who underwent curative surgery were randomly assigned to receive S-1 (80, 100, or 120 mg/day according to BSA on days 1 to 28, followed by 14 days rest, 4 courses) or UFT/LV (UFT: 300 to 600 mg/day according to BSA and, LV: 75 mg/day on days 1 to 28, followed by 7 days rest, 5 courses). Primary endpoint was DFS. Sample size was 1,480 determined with one-sided alpha of 0.05, power of 0.80, and non-inferiority margin of hazard ratio (HR) of 1.29. Results: Among 1535 enrolled patients between Apr. 2009 and Jun. 2010, 1518 patients (758 in S-1 group, 760 in UFT/LV group) were included in the efficacy analysis. Median follow-up was 41.3 months, the mean age at enrollment was 64.5 years, wide lymph node dissection (D3) was done in 79.8%, the median number of dissected lymph nodes was 17, and stage IIIA/IIIB/IIIC were 15%/71%/14%. The 3-year DFS rate was 75.5% in S-1 group and 72.5% in UFT/LV group. The HR of DFS was 0.85 (95%CI: 0.70-1.03) and non-inferiority of S-1 was demonstrated (p<0.0001). The completion rate of the protocol treatment was 76.5% in S-1 group and 72.5% in UFT/LV group. The overall incidence of grade ≥3 adverse events (AEs) in S-1 group and UFT/LV group were 16.0% and 14.4%: 4.4% and 5.5% for diarrhea, 4.9% and 3.5% for anorexia, 0.7% and 0.4% for leucopenia, 0.9% and 0.1% for anemia, 0.1% and 0.4% for thrombocytopenia, 1.2% and 1.5% for hyperbilirubinemia, 0.8% and 2.1% for AST elevation, and 1.1% and 3.3% for ALT elevation, respectively. Conclusions: Adjuvant therapy of S-1 for stage III colon cancer was demonstrated to be non-inferior in DFS to that of UFT/LV. Although AE profiles differed between S-1 group and UFT/LV group in this trial, incidence and degree of AEs were acceptable, and the completion rate of the protocol treatment was high. Adjuvant chemotherapy using S-1 will be a treatment option for stage III colon cancer. Clinical trial information: NCT00660894.

Conventional tumor grading systems based on the degree of tumor differentiation may not always be optimal because of difficulty in objective assessment and insufficient prognostic value for decision making in colorectal cancer (CRC) treatment. This study aimed to determine the importance of assessing the number of poorly differentiated clusters as the primary criterion for histologic grading of CRC. Five hundred consecutive patients with curatively resected stage II and III CRCs (2000 to 2005) were pathologically reviewed. Cancer clusters of ≥5 cancer cells and lacking a gland-like structure were counted under a ×20 objective lens in a field containing the highest number of clusters. Tumors with <5, 5 to 9, and ≥10 clusters were classified as grade (G)1, G2, and G3, respectively (n=156, 198, and 146 tumors, respectively). Five-year disease-free survival rates were 96%, 85%, and 59% for G1, G2, and G3, respectively (P<0.0001). Poorly differentiated clusters affected survival outcome independent of T and N stages and could help in more effective stratification of patients by survival outcome compared with tumor staging (Akaike information criterion, 1086.7 vs. 1117.0; Harrell concordance index, 0.73 vs. 0.67). The poorly differentiated cluster-based grading system showed a higher weighted κ coefficient for interobserver variability (5 observers) compared with conventional grading systems (mean, 0.66 vs. 0.52; range, 0.55 to 0.73 vs. 0.39 to 0.68). Our novel histologic grading system is expected to be less subjective and more informative for prognostic prediction compared with conventional tumor grading systems and TNM staging. It could be valuable in determining individualized postoperative CRC treatment.