Long-term survival and functional outcomes of laparoscopic surgery for clinical stage I ultra-low rectal cancers located within 5 cm of the anal verge: A prospective phase II trial (Ultimate trial).

OBJECTIVE: To clarify the long-term oncological outcomes and postoperative anal, urinary, and sexual functions after laparoscopic surgery for clinical stage I very low rectal carcinoma located near the anal canal. SUMMARY BACKGROUND DATA: Laparoscopic surgery is widely applied for rectal cancer; however, concerns remain, with some studies showing poorer outcomes compared to open surgery. METHODS: This single-arm, phase II trial included patients registered preoperatively from 47 institutions in Japan. The planned sample size was 300. The primary endpoint was the 3-year local recurrence rate. Anal, urinary, and sexual functions were evaluated using a prospective questionnaire. RESULTS: Three-hundred patients were registered between January 2014 and March 2017. Anus-preserving surgery was performed in 278 (93%), including 172 who underwent intersphincteric resection (58%) and 106 (36%) who underwent low anterior resection. The 3-year cumulative local recurrence rate was 6.3%. At 3 years postoperatively, 87% of patients used their own anus, and the median incontinence score improved from 12 at 3 months to 8 at 3 years. Only 5% of patients had severe incontinence (incontinence score of 16 points). Postoperative urinary function evaluation showed that International Prostate Symptom Score and Overactive Bladder Symptom Score decreased 1 week after surgery, but recovered to preoperative level 1 month after surgery. International Consultation on Incontinence Questionnaire-Sort Form remained almost stable after surgery. Sexual function evaluation using the International Index of Erectile Function-5 and International Index of Erectile Function-15 revealed that the patients had deteriorated 3 months after surgery but had recovered only slightly by 6 months. CONCLUSIONS: Laparoscopic surgery achieves feasible long-term oncological outcomes and a high rate of anus preservation with moderate anal function, and an acceptable incontinence score. While urinary function recovered rapidly, sexual function showed poor recovery.

Association between oxidative balance score and inflammatory markers in middle-aged and older Japanese people.

PURPOSE: This study aimed to investigate the association between oxidative balance score (OBS), wherein higher OBSs indicate lower oxidative stress, and high-sensitivity C-reactive protein (hs-CRP), as well as inflammatory scores, in a large cohort of Japanese adults. METHODS: In total, 9703 individuals aged 40-69 years participated in a baseline survey of a population-based cohort study in Saga, Japan (2005-2007). OBSs were calculated from 11 prooxidant and antioxidant lifestyle factors, including dietary intake, physical activity, alcohol consumption, and smoking status. Lifestyle data, including dietary intake, were obtained using a self-administered questionnaire. Adjusted geometric means of serum hs-CRP levels were calculated based on OBS quartiles, and linear trend tests were performed, with adjustments for potential confounders. In addition, an inflammatory cytokine z-score was constructed and assessed alongside individual markers. RESULTS: After adjusting for multiple confounders in both sexes, the results showed a significant inverse association between OBS and serum hs-CRP levels in both men and women. These results remained unaltered when the OBS evaluation excluded powerful prooxidants, serum ferritin, or smoking. There was also an association between OBS and lower inflammatory z-score, indicating reduced overall systemic inflammation. CONCLUSIONS: These findings suggest that a higher OBS, indicating a greater predominance of antioxidants over prooxidant exposure, is associated with lower hs-CRP levels and reduced systemic inflammation, regardless of sex.

Association of kidney function with cancer incidence and its influence on cancer risk of smoking: The Japan Multi-Institutional Collaborative Cohort Study.

The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m2 , the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m2 were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m2 were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m2 revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m2 , with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.

Dietary Carbohydrate and Fat Intakes and Risk of Mortality in the Japanese Population: the Japan Multi-Institutional Collaborative Cohort Study.

BACKGROUND: Previous cohort studies have yielded contradictory findings regarding the associations of dietary carbohydrate and fat intakes with risks of mortality. OBJECTIVES: We examined long-term associations of carbohydrate and fat intakes with mortality. METHODS: In this cohort study, 34,893 men and 46,440 women aged 35-69 y (mean body mass index of 23.7 and 22.2 kg/m2, respectively) were followed up from the baseline survey (2004-2014) to the end of 2017 or 2018. Intakes of carbohydrate, fat, and total energy were estimated using a food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for all-cause and cause-specific mortality according to percentage of energy intakes of carbohydrate and fat. RESULTS: During a mean 8.9-y follow-up, we identified 2783 deaths (1838 men and 945 women). Compared with men who consumed 50% to <55% of energy from carbohydrate, those who consumed <40% carbohydrate energy experienced a significantly higher risk of all-cause mortality (the multivariable-adjusted HR: 1.59; 95% CI: 1.19-2.12; P-trend = 0.002). Among women with 5 y or longer of follow-up, women with high-carbohydrate intake recorded a higher risk of all-cause mortality; the multivariable-adjusted HR (95% CI) was 1.71 (0.93-3.13) for ≥65% of energy from carbohydrate compared with that for 50% to <55% (P-trend = 0.005). Men with high fat intake had a higher risk of cancer-related mortality; the multivariable-adjusted HR (95% CI) for ≥35% was 1.79 (1.11-2.90) compared with that for 20% to <25%. Fat intake was marginally inversely associated with risk of all-cause and cancer-related mortality in women (P-trend = 0.054 and 0.058, respectively). CONCLUSIONS: An unfavorable association with mortality is observed for low-carbohydrate intake in men and for high-carbohydrate intake in women. High fat intake can be associated with a lower mortality risk in women among Japanese adults with a relatively high-carbohydrate intake.

Cigarette Smoking, Smoking Cessation, and Bladder Cancer Risk: A Pooled Analysis of 10 Cohort Studies in Japan.

BACKGROUND: Although cigarette smoking is an established risk factor for bladder cancer, assessment of smoking impact on bladder cancer in Asian populations has been hindered by few cohort studies conducted in Asian populations. Therefore, we investigated the risk of bladder cancer associated with smoking status, cumulative smoking intensity, and smoking cessation in Japan. METHODS: We analyzed data for 157,295 men and 183,202 women in 10 population-based cohort studies in Japan. The risk associated with smoking behaviors was estimated using Cox regression models within each study, and pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) for the incidence of bladder cancer were calculated. RESULTS: During 4,729,073 person-years of follow-up, 936 men and 325 women developed bladder cancer. In men, former smokers (HR 1.47; 95% CI, 1.18-1.82) and current smokers (HR 1.96; 95% CI, 1.62-2.38) had higher risk than never smokers. In women, current smokers had higher risk than never smokers (HR 2.35; 95% CI, 1.67-3.32). HRs in men linearly increased with increasing pack-years. Risk decreased with increasing years of smoking cessation in men, with a significant dose-response trend. Former smokers with a duration of more than 10 years after smoking cessation had no significantly increased risk compared with never smokers (HR 1.26; 95% CI, 0.97-1.63). CONCLUSION: Data from a pooled analysis of 10 population-based cohort studies in Japan clearly show an association between cigarette smoking and bladder cancer risk. The risk of smokers may approximate that of never smokers following cessation for many years.

Moderate-to-vigorous Physical Activity and Sedentary Behavior Are Independently Associated With Renal Function: A Cross-sectional Study.

BACKGROUND: Little is known about whether insufficient moderate-to-vigorous physical activity (MVPA) and longer sedentary behavior (SB) are independently associated with estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD), whether they interact with known risk factors for CKD, and the effect of replacing sedentary time with an equivalent duration of physical activity on kidney function. METHODS: We examined the cross-sectional association of MVPA and SB with eGFR and CKD in 66,603 Japanese cohort study in 14 areas from 2004 to 2013. MVPA and SB were estimated using a self-reported questionnaire, and CKD was defined as eGFR <60 mL/min/1.73 m2. Multiple linear regression analyses, logistic regression analyses, and an isotemporal substitution model were applied. RESULTS: After adjusting for potential confounders, higher MVPA and longer SB were independently associated with higher eGFR (P for trend MVPA <0.0001) and lower eGFR (P for trend SB <0.0001), and a lower odds ratio (OR) of CKD (adjusted OR of MVPA ≥20 MET·h/day, 0.76; 95% confidence interval [CI], 0.68-0.85 compared to MVPA <5 MET·h/day) and a higher OR of CKD (adjusted OR of SB ≥16 h/day, 1.81; 95% CI, 1.52-2.15 compared to SB <7 h/day), respectively. The negative association between MVPA and CKD was stronger in men, and significant interactions between sex and MVPA were detected. Replacing 1 hour of SB with 1 hour of physical activity was associated with about 3 to 4% lower OR of CKD. CONCLUSION: These findings indicate that replacing SB with physical activity may benefit kidney function, especially in men, adding to the possible evidence on CKD prevention.

Sleep duration and risk of cancer incidence and mortality: A pooled analysis of six population-based cohorts in Japan.

Sleep duration is emerging as an important modifiable risk factor for morbidity and mortality. We assessed the association between sleep duration and cancer incidence and mortality among Japanese adults using data from six population-based cohorts with 271 694 participants. During a total follow-up period of about 5.9 million person-years, we identified 40 751 incident cancer cases and 18 323 cancer deaths. We computed study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models and pooled the estimates using random-effects meta-analysis. Sleep duration of ≥10 hours (vs 7 hours) was associated with increased risk of cancer incidence among women (HR 1.19, 95% CI 1.02-1.38), but not men, and increased risk of cancer mortality among men (HR 1.18, 95% CI 1.00-1.39) and women (HR 1.44, 95% CI 1.20-1.73). Sleep duration of ≤5 hours (vs 7 hours) was not associated with cancer incidence and mortality. However, among postmenopausal women, sleep durations of both ≤5 and ≥10 hours (vs 7 hours) were associated with an increased risk of cancer mortality. Among Japanese adults, sleep duration of ≥10 hours is associated with increased risk of cancer incidence and mortality among women and cancer mortality among men.

Alcohol intake and stomach cancer risk in Japan: A pooled analysis of six cohort studies.

The association between alcohol intake and stomach cancer risk remains controversial. We undertook a pooled analysis of data from six large-scale Japanese cohort studies with 256 478 participants on this topic. Alcohol intake as ethanol was estimated using a validated questionnaire. The participants were followed for incidence of stomach cancer. We calculated study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for stomach cancer according to alcohol intake using a Cox regression model. Summary HRs were estimated by pooling the study-specific HRs using a random-effects model. During 4 265 551 person-years of follow-up, 8586 stomach cancer cases were identified. In men, the multivariate-adjusted HRs (95% CIs) of stomach cancer were 1.00 (0.87-1.15) for occasional drinkers, and 1.00 (0.91-1.11) for <23 g/d, 1.09 (1.01-1.18) for 23 to <46 g/d, 1.18 (1.09-1.29) for 46 to <69 g/d, 1.21 (1.05-1.39) for 69 to <92 g/d, and 1.29 (1.11-1.51) for ≥92 g/d ethanol in regular drinkers compared with nondrinkers. In women, the multivariate-adjusted HRs were 0.93 (0.80-1.08) for occasional drinkers, and 0.85 (0.74-0.99) for <23 g/d, and 1.22 (0.98-1.53) for ≥23 g/d in regular drinkers compared with nondrinkers. The HRs for proximal and distal cancer in drinkers vs nondrinkers were 1.69 (1.15-2.47) and 1.24 (0.99-1.55) for ≥92 g/d in men, and 1.60 (0.76-3.37) and 1.18 (0.88-1.57) for ≥23 g/d in women, respectively. Alcohol intake increased stomach cancer risk in men, and heavy drinkers showed a greater point estimate of risk for proximal cancer than for distal cancer.

Adult height in relation to the risk of colorectal cancer among the Japanese population: an evaluation based on systematic review and meta-analysis.

OBJECTIVE: The association between adult-attained height and risk of colorectal cancer remains elusive among the Japanese population. We performed a systematic review and meta-analysis of epidemiological studies in Japan. METHODS: We systematically searched the MEDLINE (PubMed) and Ichushi databases and complemented it with manual search to identify eligible studies. We extracted relative risks or odds ratios from the selected studies and conducted meta-analysis to estimate the summary relative risk with 95% confidence interval. We made the final judgment based on a consensus of the research group members considering both epidemiological evidence and biological plausibility. RESULTS: This systematic review identified four cohort and one case-control studies among the Japanese. The meta-analysis of these five studies showed the summary relative risk of 1.21 (95% confidence interval: 1.07-1.35) of overall colorectal cancer for the highest vs. lowest categories of height. In the analysis by the cancer subsite, the association was significant for colon cancer with a summary relative risk of 1.26 (95% confidence interval: 1.10-1.45) but not for rectal cancer 1.05 (95% confidence interval: 0.71-1.54). In the analysis by sex, tall stature was associated with a significantly increased risk of overall colorectal cancer in both sexes; the summary relative risk was 1.21 (95% confidence interval: 1.04-1.41) in men and 1.20 (95% confidence interval: 1.00-1.44) in women, respectively. CONCLUSIONS: The evidence to support that adult-attained height is associated with increased risk of colorectal cancer (colon cancer) among the Japanese population is 'probable'.

Medium-term oncological outcomes of totally laparoscopic colectomy with intracorporeal anastomosis for right-sided and left-sided colon cancer: propensity score matching analysis.

BACKGROUND: This retrospective study aimed to compare long-term oncological outcomes between laparoscopic-assisted colectomy (LAC) with extracorporeal anastomosis (EA) and totally laparoscopic colectomy (TLC) with intracorporeal anastomosis (IA) for colon cancers, including right- and left-sided colon cancers. METHODS: Patients with stage I-III colon cancers who underwent elective laparoscopic colectomy between January 2013 and December 2017 were analyzed retrospectively. Patients converted from laparoscopic to open surgery and R1/R2 resection were excluded. Propensity score matching (PSM) analysis (1:1) was performed to overcome patient selection bias. RESULTS: A total of 388 patients were reviewed. After PSM, 83 patients in the EA group and 83 patients in the IA group were compared. Median follow-up was 56.5 months in the EA group and 55.5 months in the IA group. Estimated 3-year overall survival (OS) did not differ significantly between the EA group (86.6%; 95% confidence interval (CI), 77.4-92.4%) and IA group (84.8%; 95%CI, 75.0-91.1%; P = 0.68). Estimated 3-year disease-free survival (DFS) likewise did not differ significantly between the EA group (76.4%; 95%CI, 65.9-84.4%) and IA group (81.0%; 95%CI, 70.1-88.2%; P = 0.12). CONCLUSION: TLC with IA was comparable to LAC with EA in terms of 3-year OS and DFS. TLC with IA thus appears to offer an oncologically feasible procedure.

Syntheses of novel pyridine-based low-molecular-weight luminogens possessing aggregation-induced emission enhancement (AIEE) properties.

Novel pyridine-based fluorescing compounds, viz. pyrido[1,2-a]pyrrolo[3,4-d]pyrimidines 3a,b and N-methyl-4-((pyridin-2-yl)amino)maleimides 4a-e, were selectively prepared by a one-pot reaction between a functionalized maleimide and 2-aminopyridines with electron-donating or electron-withdrawing groups at position 5 and were investigated photophysically and computationally. The photophysical studies revealed that all the synthesized compounds exhibited fluorescence in organic solvents, while N-methyl-4-((pyridin-2-yl)amino)-substituted maleimide derivatives 4a-e, which are based on an acceptor-donor-acceptor (A-D-A) system, exhibited aggregation-induced emission enhancement (AIEE) properties in aqueous media. Compounds 4a and 4e, bearing electron-withdrawing groups (Br and CF3, respectively) showed 7.0 and 15 times fluorescence enhancement. Time-dependent density functional theory (TD-DFT) calculations were performed to gain better insight into the electronic nature of the compounds with and without AIEE properties.

Alcohol consumption and breast cancer risk in Japan: A pooled analysis of eight population-based cohort studies.

Although alcohol consumption is reported to increase the incidence of breast cancer in European studies, evidence for an association between alcohol and breast cancer in Asian populations is insufficient. We conducted a pooled analysis of eight large-scale population-based prospective cohort studies in Japan to evaluate the association between alcohol (both frequency and amount) and breast cancer risk with categorization by menopausal status at baseline and at diagnosis. Estimated hazard ratios (HR) and 95% confidence intervals were calculated in the individual cohorts and combined using random-effects models. Among 158 164 subjects with 2 369 252 person-years of follow-up, 2208 breast cancer cases were newly diagnosed. Alcohol consumption had a significant association with a higher risk of breast cancer in both women who were premenopausal at baseline (regular drinker compared to nondrinker: HR 1.37, 1.04-1.81, ≥23 g/d compared to 0 g/d: HR 1.74, 1.25-2.43, P for trend per frequency category: P = .017) and those who were premenopausal at diagnosis (≥23 g/d compared to 0 g/d: HR 1.89, 1.04-3.43, P for trend per frequency category: P = .032). In contrast, no significant association was seen in women who were postmenopausal at baseline or at diagnosis, despite a substantial number of subjects and long follow-up period. Our results revealed that frequent and high alcohol consumption are both risk factors for Asian premenopausal breast cancer, similarly to previous studies in Western countries. The lack of a clear association in postmenopausal women in our study warrants larger investigation in Asia.

Smoking and colorectal cancer: A pooled analysis of 10 population-based cohort studies in Japan.

Smoking has been consistently associated with the risk of colorectal cancer (CRC) in Western populations; however, evidence is limited and inconsistent in Asian people. To assess the association of smoking status, smoking intensity and smoking cessation with colorectal risk in the Japanese population, we performed a pooled analysis of 10 population-based cohort studies. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox's proportional hazards model and then pooled using a random-effects model. Among 363 409 participants followed up for 2 666 004 person-years, 9232 incident CRCs were identified. In men, compared with never smokers, ever smokers showed higher risk of CRC. The HRs (95% CI) were 1.19 (1.10-1.29) for CRC, 1.19 (1.09-1.30) for colon cancer, 1.28 (1.13-1.46) for distal colon cancer and 1.21 (1.07-1.36) for rectal cancer. Smoking was associated with risk of CRC in a dose-response manner. In women, compared with never smokers, ever smokers showed increased risk of distal colon cancer (1.47 [1.19-1.82]). There was no evidence of a significant gender difference in the association of smoking and CRC risk. Our results confirm that smoking is associated with an increased risk of CRC, both overall and subsites, in Japanese men and distal colon cancer in Japanese women.

Whole-body insulin resistance and energy expenditure indices, serum lipids, and skeletal muscle metabolome in a state of lipoprotein lipase overexpression.

INTRODUCTION: Overexpression of lipoprotein lipase (LPL) protects against high-fat-diet (HFD)-induced obesity and insulin resistance in transgenic rabbits; however, the molecular mechanisms remain unclear. Skeletal muscle is a major organ responsible for insulin-stimulated glucose uptake and energy expenditure. OBJECTIVES: The main purpose of the current study was to examine the effects of the overexpression of LPL on the skeletal muscle metabolomic profiles to test our hypothesis that the mitochondrial oxidative metabolism would be activated in the skeletal muscle of LPL transgenic rabbits and that the higher mitochondrial oxidative metabolism activity would confer better phenotypic metabolic outcomes. METHODS: Under a HFD, insulin resistance index was measured using the intravenous glucose tolerance test, and total energy expenditure (TEE) was measured by doubly-labeled water in control and LPL transgenic rabbits (n = 12, each group). Serum lipids, such as triglycerides and free fatty acid, were also measured. The skeletal muscle metabolite profile was analyzed using capillary electrophoresis time-of flight mass spectrometry in the two groups (n = 9, each group). A metabolite set enrichment analysis (MSEA) with muscle metabolites and a false discovery rate q < 0.2 was performed to identify significantly different metabolic pathways between the 2 groups. RESULTS: The triglycerides and free fatty acid levels and insulin resistance index were lower, whereas the TEE was higher in the LPL transgenic rabbits than in the control rabbits. Among 165 metabolites detected, the levels of 37 muscle metabolites were significantly different between the 2 groups after false discovery rate correction (q < 0.2). The MSEA revealed that the TCA cycle and proteinogenic amino acid metabolism pathways were significantly different between the 2 groups (P < 0.05). In the MSEA, all four selected metabolites for the TCA cycle (2-oxoglutaric acid, citric acid, malic acid, fumaric acid), as well as eight selected metabolites for proteinogenic amino acid metabolism (asparagine, proline, methionine, phenylalanine, histidine, arginine, leucine, isoleucine) were consistently increased in the transgenic rabbits compared with control rabbits, suggesting that these two metabolic pathways were activated in the transgenic rabbits. Some of the selected metabolites, such as citric acid and methionine, were significantly associated with serum lipids and insulin resistance (P < 0.05). CONCLUSION: The current results suggest that the overexpression of LPL may lead to increased activities of TCA cycle and proteinogenic amino acid metabolism pathways in the skeletal muscle, and these enhancements may play an important role in the biological mechanisms underlying the anti-obesity/anti-diabetes features of LPL overexpression.

A genome-wide association study on confection consumption in a Japanese population: the Japan Multi-Institutional Collaborative Cohort Study.

Differences in individual eating habits may be influenced by genetic factors, in addition to cultural, social or environmental factors. Previous studies suggested that genetic variants within sweet taste receptor genes family were associated with sweet taste perception and the intake of sweet foods. The aim of this study was to conduct a genome-wide association study (GWAS) to find genetic variations that affect confection consumption in a Japanese population. We analysed GWAS data on confection consumption using 14 073 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a semi-quantitative FFQ to estimate food intake that was validated previously. Association of the imputed variants with confection consumption was performed by linear regression analysis with adjustments for age, sex, total energy intake and principal component analysis components 1-3. Furthermore, the analysis was repeated adjusting for alcohol intake (g/d) in addition to the above-described variables. We found 418 SNP located in 12q24 that were associated with confection consumption. SNP with the ten lowest P-values were located on nine genes including at the BRAP, ACAD10 and aldehyde dehydrogenase 2 regions on 12q24.12-13. After adjustment for alcohol intake, no variant was associated with confections intake with genome-wide significance. In conclusion, we found a significant number of SNP located on 12q24 genes that were associated with confections intake before adjustment for alcohol intake. However, all of them lost statistical significance after adjustment for alcohol intake.

Effects of Helicobacter pylori eradication on gastric cancer incidence in the Japanese population: a systematic evidence review.

BACKGROUND: In Japan, there are ongoing efforts to shift the gastric cancer prevention and control policy priorities from barium-based screening to Helicobacter pylori (H. pylori)-oriented primary prevention. A comprehensive summary of the evidence regarding the effects of H. pylori eradication on the risk of gastric cancer could inform policy decisions. METHODS: We conducted a systematic review and meta-analysis of published studies evaluating the effectiveness of H. pylori eradication for the prevention of gastric cancer in otherwise healthy individuals (primary prevention) and early gastric cancer patients (tertiary prevention). RESULTS: In total, 19 studies were included. Three moderate-quality observational cohort studies showed that H. pylori eradication may be associated with a decreased risk of gastric cancer in healthy asymptomatic Japanese people. There is moderate certainty regarding the effectiveness of H. pylori eradication in patients with gastrointestinal diseases, such as peptic ulcers. A meta-analysis of 10 observational studies with otherwise healthy individuals (mainly peptic ulcer patients) yielded an overall odds ratio of 0.34 (95% CI: 0.25-0.46). Regarding tertiary prevention, the overall odds ratio for developing metachronous gastric cancer was 0.42 (95% CI: 0.35-0.51) in the eradication group in a meta-analysis of nine studies involving early gastric cancer patients who underwent endoscopic resection. CONCLUSION: H. pylori eradication is effective in preventing gastric cancer in the Japanese population, regardless of symptoms. Well-designed, large cohort studies are warranted to determine the long-term efficacy and safety of H. pylori eradication in the context of reducing the gastric cancer burden through population-based screening and treatment.

Differential Effect of Polymorphisms on Body Mass Index Across the Life Course of Japanese: The Japan Multi-Institutional Collaborative Cohort Study.

BACKGROUND: Obesity is a reported risk factor for various health problems. Genome-wide association studies (GWASs) have identified numerous independent loci associated with body mass index (BMI). However, most of these have been focused on Europeans, and little evidence is available on the genetic effects across the life course of other ethnicities. METHODS: We conducted a cross-sectional study to examine the associations of 282 GWAS-identified single nucleotide polymorphisms with three BMI-related traits, current BMI, BMI at 20 years old (BMI at 20), and change in BMI (BMI change), among 11,586 Japanese individuals enrolled in the Japan Multi-Institutional Collaborative Cohort study. Associations were examined using multivariable linear regression models. RESULTS: We found a significant association (P < 0.05/282 = 1.77 × 10-4) between BMI and 11 polymorphisms in or near FTO, BDNF, TMEM18, HS6ST3, and BORCS7. The trend was similar between current BMI and BMI change, but differed from that of the BMI at 20. Among the significant variants, those on FTO were associated with all BMI traits, whereas those on TMEM18 and HS6SR3 were only associated with BMI at 20. The association of FTO loci with BMI remained, even after additional adjustment for dietary energy intake. CONCLUSIONS: Previously reported BMI-associated loci discovered in Europeans were also identified in the Japanese population. Additionally, our results suggest that the effects of each loci on BMI may vary across the life course and that this variation may be caused by the differential effects of individual genes on BMI via different pathways.

Study Profile of the Japan Multi-institutional Collaborative Cohort (J-MICC) Study.

BACKGROUND: The Japan Multi-institutional Collaborative Cohort (J-MICC) study was launched in 2005 to examine gene-environment interactions in lifestyle-related diseases, including cancers, among the Japanese. This report describes the study design and baseline profile of the study participants. METHODS: The participants of the J-MICC Study were individuals aged 35 to 69 years enrolled from respondents to study announcements in specified regions, inhabitants attending health checkup examinations provided by local governments, visitors at health checkup centers, and first-visit patients at a cancer hospital in Japan. At the time of the baseline survey, from 2005 to 2014, we obtained comprehensive information regarding demographics, education, alcohol consumption, smoking, sleeping, exercise, food intake frequency, medication and supplement use, personal and family disease history, psychological stress, and female reproductive history and collected peripheral blood samples. RESULTS: The baseline survey included 92,610 adults (mean age: 55.2 [standard deviation, 9.4] years, 44.1% men) from 14 study regions in 12 prefectures. The participation rate was 33.5%, with participation ranging from 19.7% to 69.8% in different study regions. The largest number of participants was in the age groups of 65-69 years for men and 60-64 years for women. There were differences in body mass index, educational attainment, alcohol consumption, smoking, and sleep duration between men and women. CONCLUSIONS: The J-MICC Study collected lifestyle and clinical data and biospecimens from over 90,000 participants. This cohort is expected to be a valuable resource for the national and international scientific community in providing evidence to support longer healthy lives.

Closure of enterotomy after side-to-side ileocolic anastomosis with two barbed sutures in totally laparoscopic colectomy for right-sided colon cancer.

Good short-term outcomes of intracorporeal ileocolic anastomosis (IIA) in totally laparoscopic colectomy for right-sided colon cancer (TLRC) have been shown in many reports, but no standardized technique for enterotomy closure after stapled side-to-side ileocolic anastomosis has so far been established. We retrospectively compared the short-term outcomes between 13 consecutive patients receiving either TLRC with IIA by conventional enterotomy closure (n = 6) or closure of the enterotomy using two barbed sutures (CEBAS) (n = 7) from July 2019 to April 2020. No anastomotic bleeding or leakage was observed in either group. Time to enterotomy closure was significantly shorter with the CEBAS method (16.5 ± 3.7 min) than with the conventional method (24.5 ± 4.7 min, p = 0.0059). The CEBAS method in TLRC with IIA was thus found to be technically feasible and it might reduce the stress associated with intracorporeal enterotomy closure.

The interaction between ABCA1 polymorphism and physical activity on the HDL-cholesterol levels in a Japanese population.

Few studies have investigated the interactions between HDL-C-related SNPs identified by genome-wide association (GWA) study and physical activity (PA) on HDL-C. First, we conducted a sex-stratified GWA study in a discovery sample (2,231 men and 2,431 women) and replication sample (2,599 men and 3,109 women) to identify SNPs influencing log-transformed HDL-C in Japanese participants in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. We also replicated previously reported HDL-C-related SNPs in a combined (discovery plus replication) sample (4,830 men and 5,540 women). We then analyzed the interactions of the HDL-C-related SNPs with PA on HDL-C. The sex-stratified GWA analyses identified 11 and 10 HDL-C-related SNPs in men and women as targets for an interaction analysis. Among these, only one interaction of ABCA1 rs1883025 with PA was statistically significant in men, after Bonferroni correction [P-interaction = 0.001 (α = 0.05/21 = 0.002)]. The per-major-allele (C allele) increase in log-transformed HDL-C was lost in men with low PA (ß = 0.008) compared with those with medium (ß = 0.032) or high PA (ß = 0.034). These findings suggest that the benefit of carrying a C allele of ABCA1 rs1883025 on enhancing HDL-C may be attenuated in inactive men.