Publications by authors named "Keitaro Matsuo"

673 Publications

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

Cancer Sci 2021 Oct 24. Epub 2021 Oct 24.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

The association between alcohol intake and stomach cancer risk remains controversial. We therefore performed 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, 8,586 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/day, 1.09 (1.01-1.18) for 23 to <46 g/day, 1.18 (1.09-1.29) for 46 to <69 g/day, 1.21 (1.05-1.39) for 69 to <92 g/day, and 1.29 (1.11-1.51) for ≥92 g/day 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/day, and 1.22 (0.98-1.53) for ≥23 g/day in regular drinkers compared with nondrinkers. The HRs for proximal and distal cancer in drinkers versus nondrinkers were 1.69 (1.15-2.47) and 1.24 (0.99-1.55) for ≥92 g/day in men, and 1.60 (0.76-3.37) and 1.18 (0.88-1.57) for ≥23 g/day 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.15172DOI Listing
October 2021

Moderate-to-vigorous physical activity and sedentary behavior are independently associated with renal function: a cross-sectional study.

J Epidemiol 2021 Oct 16. Epub 2021 Oct 16.

Department of Preventive Medicine, Tokushima University Graduate School of Biomedical Sciences.

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 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 m. 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<0.0001) and lower eGFR (P<0.0001), and a lower odds ratio (OR) of CKD (adjusted OR of MVPA≥20 MET·h/day: 0.76 [95%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.

Conclusions: These findings indicate that replacing SB with physical activity may benefit kidney function, especially in men, adding to the possible evidence on CKD prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2188/jea.JE20210155DOI Listing
October 2021

Significance of Antimicrobial Prophylaxis for the Prevention of Early-Onset Pneumonia After Radical Esophageal Cancer Resection: A Retrospective Analysis of 356 Patients Undergoing Thoracoscopic Esophagectomy.

Ann Surg Oncol 2021 Sep 30. Epub 2021 Sep 30.

Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.

Background: Postoperative pneumonia is a common complication after esophagectomy and is associated with a high mortality rate. Although many randomized, controlled trials have been conducted on the prevention of postoperative pneumonia, little attention has been paid to the efficacy of antimicrobial prophylaxis. The purpose of this study was to investigate the impact of antimicrobial prophylaxis on the prevention of postoperative pneumonia.

Methods: Data of patients with esophageal cancer who underwent thoracoscopic esophagectomy between 2016 and 2020 were collected. Early-period patients received cefazolin (CEZ) per protocol as antimicrobial prophylaxis (n = 250), and later-period patients received ampicillin/sulbactam (ABPC/SBT) (n = 106) because of the unavailability of CEZ in Japan. The incidence of pneumonia was compared between treatments in this quasi-experimental setting. Pneumonia detected by routine computed tomography (CT) on postoperative Days 5-6 was defined as early-onset pneumonia, and pneumonia that developed later was defined as late-onset pneumonia.

Results: The incidence of early-onset pneumonia was significantly lower (3.8% vs. 13.6%, P = 0.006), and the median length of postoperative hospital stay was significantly shorter (17 vs. 20 days, P < 0.001) in the ABPC/SBT group than in the CEZ group. The incidence of late-onset pneumonia was similar between groups (9.4% vs. 10.0%, P = 0.870). The incidence of Clostridioides difficile infections and the incidence of multidrug-resistant organisms were similar between groups. Multivariate analyses consistently showed the superiority of ABPC/SBT to CEZ in preventing early-onset pneumonia (odds ratio: 0.20, P = 0.006).

Conclusions: ABPC/SBT after esophagectomy was better at preventing early-onset pneumonia compared with CEZ and was feasible regarding the development of antimicrobial resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-021-10867-5DOI Listing
September 2021

Sex-specific Relationship between Stress Coping Strategies and All-Cause Mortality: Japan Multi-Institutional Collaborative Cohort Study.

J Epidemiol 2021 Sep 25. Epub 2021 Sep 25.

Department of Preventive Medicine, Nagoya University Graduate School of Medicine.

Background: Stress coping strategies are related to health outcomes. However, there is no clear evidence for sex differences between stress-coping strategies and mortality. We investigated the relationship between all-cause mortality and stress-coping strategies, focusing on sex differences among Japanese adults.

Methods: A total of 79,580 individuals aged 35-69 years participated in the Japan Multi-Institutional Collaborative Cohort Study between 2004 and 2014 and were followed up for mortality. The frequency of use of the five coping strategies was assessed using a questionnaire. Sex-specific, multivariable-adjusted hazard ratios (HRs) for using each coping strategy "sometimes," and "often/very often" (versus "very few" use) were computed for all-cause mortality. Furthermore, relationships were analyzed in specific follow-up periods when the proportion assumption was violated.

Results: During the follow-up (median: 8.5 years), 1,861 mortalities were recorded. In women, three coping strategies were related to lower total mortality. The HRs (95% confidence intervals) for "sometimes" were 0.81 (0.67-0.97) for emotional expression, 0.79 (0.66-0.95) for emotional support-seeking, and 0.80 (0.66-0.98) for disengagement. Men who "sometimes" used emotional expression and sometimes or often used problem-solving and positive reappraisal had a 15-41% lower HRs for all-cause mortality. However, those relationships were dependent on the follow-up period. There was evidence that sex modified the relationships between emotional support-seeking and all-cause mortality (p for interaction = 0.03).

Conclusions: In a large Japanese population, selected coping strategies were associated with all-cause mortality. The relationship of emotional support-seeking was different between men and women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2188/jea.JE20210220DOI Listing
September 2021

International strategy in cancer epidemiology: Japan's involvement in global projects and future role.

Glob Health Med 2021 Aug;3(4):187-195

Division of Cohort Research, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

In recent years, collaboration among researchers in the field of cancer epidemiology has been accelerating in various forms. Here, we review recent trends in international collaborative research activities in the cancer epidemiology field in Japan. These include not only support for other countries with less developed cancer statistics infrastructures, but also large-scale compilations and international comparisons through collaborative studies, as well as integration with analytical epidemiology and clinical research. Formation of international cohort consortia and estimates of cancer and risk factors in each country have contributed to raising the skill levels of cancer epidemiologists as well as to expanding research networks and activities among cancer epidemiologists. Molecular and genome epidemiological studies on cancer have progressed over decades and these continue to increase in size and dimension. Application of evidence from this area in prevention is still underway and needs further effort. Japanese epidemiologists have great potential to assume international leadership roles by taking advantage of the uniqueness, originality and characteristics of Japanese cohorts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.35772/ghm.2021.01002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403262PMC
August 2021

Body mass index and type 2 diabetes and breast cancer survival: a Mendelian randomization study.

Am J Cancer Res 2021 15;11(8):3921-3934. Epub 2021 Aug 15.

Institute of Biomedical Sciences, Academia Sinica Taipei, Taiwan.

The causal relationship between body mass index (BMI) and type 2 diabetes (T2D) and breast cancer prognosis is still ambiguous. The aim of this study was to investigate the prognostic effect of BMI and T2D on breast cancer disease-free survival (DFS) among Asian individuals. In this two-sample Mendelian randomization (MR) study, the instrumental variables (IVs) were identified using a genome-wide association study (GWAS) among 24,000 participants in the Taiwan Biobank. Importantly, the validity of these IVs was confirmed with a previous large-scale GWAS (Biobank Japan Project, BBJ). In this study, we found that a genetic predisposition toward higher BMI (as indicated by BMI IVs, F = 86.88) was associated with poor breast cancer DFS (hazard ratio [HR] = 6.11; P < 0.001). Furthermore, higher level of genetically predicted T2D (as indicated by T2D IVs) was associated with an increased risk of recurrence of and mortality from breast cancer (HR = 1.43; P < 0.001). Sensitivity analyses, including the weighted-median approach, MR-Egger regression, Radial regression and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) supported the consistency of our findings. Finally, the causal relationship between BMI and poor breast cancer prognosis was confirmed in a prospective cohort study. Our MR analyses demonstrated the causal relationship between the genetic prediction of elevated BMI and a greater risk of T2D with poor breast cancer prognosis. BMI and T2D have important clinical implications and may be used as prognostic indicators of breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414374PMC
August 2021

Reply to P. Kaul et al.

J Clin Oncol 2021 Sep 10:JCO2101554. Epub 2021 Sep 10.

Yasuhisa Hasegawa, MD, PhD, Asahi University Hospital, Gifu, Japan; Kiyoaki Tsukahara, MD, PhD, Tokyo Medical University, Tokyo, Japan; Seiichi Yoshimoto, MD, PhD, National Cancer Center Hospital, Tokyo, Japan; Kouki Miura, MD, PhD, International University of Health and Welfare, Mita Hospital, Tokyo, Japan; Junkichi Yokoyama, MD, PhD, Nadogaya Hospital, Kashiwa, Japan; Shigeru Hirano, MD, PhD, Kyoto Prefectural University of Medicine, Kyoto, Japan; Hirokazu Uemura, MD, PhD, Nara Medical University, Kashihara, Japan; Masashi Sugasawa, MD, PhD, Saitama Medical University International Medical Center, Hidaka, Japan; Tomokazu Yoshizaki, MD, PhD, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan; Akihiro Homma, MD, PhD, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Kazuaki Chikamatsu, MD, PhD, Gunma University School of Medicine, Maebashi, Japan; Mikio Suzuki, MD, PhD, University of the Ryukyus Faculty of Medicine, Okinawa, Japan; Akihiro Shiotani, MD, PhD, National Defense Medical College, Tokorozawa, Japan; Takashi Matsuzuka, MD, PhD, Asahi University Hospital, Gifu, Japan; Naoyuki Kohno, MD, PhD, Kyorin University School of Medicine, Tokyo, Japan; Masakazu Miyazaki, MD, Nara Prefecture General Medical Center, Nara, Japan; Isao Oze, MD, PhD, and Keitaro Matsuo, MD, PhD, Aichi Cancer Center Research Institute, Nagoya Japan; Shigeru Kosuda, MD, PhD, Kouseikai General Clinic and Hospital, Kawagoe, Japan; and Yasushi Yatabe, MD, PhD, National Cancer Center Hospital, Tokyo, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.21.01554DOI Listing
September 2021

Should the Supraclavicular Lymph Nodes be Considered Regional Lymph Nodes in Cervical Esophageal Cancer?

Ann Surg Oncol 2021 Sep 3. Epub 2021 Sep 3.

Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.

Background: The importance of supraclavicular lymph node (SCLN) metastases in esophageal cancer (EC) remains unknown. Few studies have reported on the prognostic impact of SCLN metastases on patients with cervical EC (CEC). This study aimed to investigate whether SCLNs should be considered regional lymph nodes and be dissected in patients with CEC.

Methods: This retrospective study enrolled 835 consecutive patients who underwent radical esophagectomy. Of these patients, 67 underwent radical surgery for CEC. These 67 patients were divided into three groups based on the presence of lymph node metastases with or without metastatic SCLNs or the absence of lymph node metastases.

Results: Of the 67 patients, 23 (34.3%) did not have metastatic lymph nodes (pN-negative group), 27 (40.3%) had metastatic lymph nodes except for metastatic SCLNs (pN-positive group without metastatic SCLN), and 17 (25.4%) had metastatic lymph nodes including metastatic SCLNs (pN-positive group with metastatic SCLNs). The 5-year overall survival rate was 58.4% for the pN-negative group, 46.2% for the pN-positive group without metastatic SCLNs, and 7.8% for the pN-positive group with metastatic SCLNs. The pN-positive group with metastatic SCLNs tended to show residual tumor cells and complications after surgery. The presence of metastatic SCLNs was a significantly poor prognostic factor (p = 0.004). The efficacy index was lowest for the lymph nodes in the supraclavicular region.

Conclusions: The prognosis of the CEC patients with metastatic SCLNs was dismal. Although the cervical esophagus is located adjacent to the SCLNs, the SCLNs may be considered extra-regional lymph nodes in patients with CEC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-021-10664-0DOI Listing
September 2021

Coffee and tea consumption and mortality from all causes, cardiovascular disease and cancer: a pooled analysis of prospective studies from the Asia Cohort Consortium.

Int J Epidemiol 2021 Sep 1. Epub 2021 Sep 1.

Department of Public Health Sciences, University of Chicago, Chicago, IL, USA.

Background: Accumulating evidence suggests that consuming coffee may lower the risk of death, but evidence regarding tea consumption in Asians is limited. We examined the association between coffee and tea consumption and mortality in Asian populations.

Methods: We used data from 12 prospective cohort studies including 248 050 men and 280 454 women from the Asia Cohort Consortium conducted in China, Japan, Korea and Singapore. We estimated the study-specific association of coffee, green tea and black tea consumption with mortality using Cox proportional-hazards regression models and the pooled study-specific hazard ratios (HRs) using a random-effects model.

Results: In total, 94 744 deaths were identified during the follow-up, which ranged from an average of 6.5 to 22.7 years. Compared with coffee non-drinkers, men and women who drank at least five cups of coffee per day had a 24% [95% confidence interval (CI) 17%, 29%] and a 28% (95% CI 19%, 37%) lower risk of all-cause mortality, respectively. Similarly, we found inverse associations for coffee consumption with cardiovascular disease (CVD)-specific and cancer-specific mortality among both men and women. Green tea consumption was associated with lower risk of mortality from all causes, CVD and other causes but not from cancer. The association of drinking green tea with CVD-specific mortality was particularly strong, with HRs (95% CIs) of 0.79 (0.68, 0.91) for men and 0.78 (0.68, 0.90) for women who drank at least five cups per day of green tea compared with non-drinkers. The association between black tea consumption and mortality was weak, with no clear trends noted across the categories of consumption.

Conclusions: In Asian populations, coffee consumption is associated with a lower risk of death overall and with lower risks of death from CVD and cancer. Green tea consumption is associated with lower risks of death from all causes and CVD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ije/dyab161DOI Listing
September 2021

Population-Based Impact of Smoking, Drinking, and Genetic Factors on HDL-Cholesterol Levels in J-MICC Study Participants.

J Epidemiol 2021 Aug 21. Epub 2021 Aug 21.

Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN.

Background: Environmental and genetic factors are suggested to exhibit factor-based association with HDL-cholesterol (HDL-C) levels. However, the population-based effects of environmental and genetic factors have not been compared clearly. We conducted a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study to evaluate the population-based impact of smoking, drinking, and genetic factors on low HDL-C.

Methods: Data from 11,498 men and women aged 35-69 years were collected for a genome-wide association study (GWAS). Sixty-five HDL-C-related SNPs with genome-wide significance (P < 5 × 10) were selected from the GWAS catalog, and seven representative SNPs were defined, and the population-based impact was estimated using population attributable fraction (PAF).

Results: We found that smoking, drinking, daily activity, habitual exercise, egg intake, BMI, age, sex and the SNPs CETP rs3764261, APOA5 rs662799, LIPC rs1800588, LPL rs328, ABCA1 rs2575876, LIPG rs3786247, and APOE rs429358 were associated with HDL-C levels. The gene-environmental interactions on smoking and drinking were not statistically significant. The PAF for low HDL-C was the highest in men (63.2%) and in rs3764261 (31.5%) of the genetic factors, and the PAFs of smoking and drinking were 23.1% and 41.8%, respectively.

Conclusions: The present study showed that the population-based impact of genomic factor CETP rs3764261 for low HDL-C was higher than that of smoking and lower than that of drinking.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2188/jea.JE20210142DOI Listing
August 2021

Early Prediction of a Serious Postoperative Course in Perihilar Cholangiocarcinoma: Trajectory Analysis of the Comprehensive Complication Index.

Ann Surg 2021 Aug 13. Epub 2021 Aug 13.

Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan Division of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Objective: To visualize the postoperative clinical course using the comprehensive complication index (CCI) and to propose an early alarming sign for subsequent serious outcomes in perihilar cholangiocarcinoma.

Background: Surgery for this disease carries a high risk of morbidity and mortality. The developmental course of the overall morbidity burden and its clinical utility are unknown.

Methods: Patients who underwent major hepatectomy for perihilar cholangiocarcinoma between 2010 and 2019 were reviewed retrospectively. All postoperative complications were evaluated according to the Clavien-Dindo classification (CDC), and the CCI was calculated on a daily basis until postoperative day 14 to construct an accumulating graph as a trajectory. Group-based trajectory modeling was conducted to categorize the trajectory into clinically distinct patterns and the predictive power of early CCI for a subsequent serious course was assessed.

Results: A total of 4230 complications occurred in the 484 study patients (CDC grade I, n=27; II, n=132; IIIa, n=290; IIIb, n=4; IVa, n=21; IVb, n=1; and V, n=9). The trajectory was categorized into 3 patterns: mild (n=209), moderate (n=235), and severe (n=40) morbidity courses. The 90-day mortality rate significantly differed among the courses: 0%, 0.9%, and 17.5%, respectively (P<0.001). The cutoff values of the CCI on postoperative days 1, 4, and 7 for predicting a severe morbidity course were 15.0, 28.5, and 40.6 with areas under the curves of 0.780, 0.924, and 0.984, respectively.

Conclusions: The CCI could depict the chronological increase in the overall morbidity burden, categorized into 3 patterns. Early CCI potentially predicted sequential progression to serious outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000005162DOI Listing
August 2021

A Personal Breast Cancer Risk Stratification Model Using Common Variants and Environmental Risk Factors in Japanese Females.

Cancers (Basel) 2021 Jul 28;13(15). Epub 2021 Jul 28.

Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.

Personalized approaches to prevention based on genetic risk models have been anticipated, and many models for the prediction of individual breast cancer risk have been developed. However, few studies have evaluated personalized risk using both genetic and environmental factors. We developed a risk model using genetic and environmental risk factors using 1319 breast cancer cases and 2094 controls from three case-control studies in Japan. Risk groups were defined based on the number of risk alleles for 14 breast cancer susceptibility loci, namely low (0-10 alleles), moderate (11-16) and high (17+). Environmental risk factors were collected using a self-administered questionnaire and implemented with harmonization. Odds ratio (OR) and C-statistics, calculated using a logistic regression model, were used to evaluate breast cancer susceptibility and model performance. Respective breast cancer ORs in the moderate- and high-risk groups were 1.69 (95% confidence interval, 1.39-2.04) and 3.27 (2.46-4.34) compared with the low-risk group. The C-statistic for the environmental model of 0.616 (0.596-0.636) was significantly improved by combination with the genetic model, to 0.659 (0.640-0.678). This combined genetic and environmental risk model may be suitable for the stratification of individuals by breast cancer risk. New approaches to breast cancer prevention using the model are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13153796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345053PMC
July 2021

PON1 Q192R is associated with high platelet reactivity with clopidogrel in patients undergoing elective neurointervention: A prospective single-center cohort study.

PLoS One 2021 5;16(8):e0254067. Epub 2021 Aug 5.

Department of Neurology, Graduate School of Medical Sciences, Neurological Institute, Kyushu University, Fukuoka, Japan.

Background And Purpose: The impact of the paraoxonase-1 (PON1) polymorphism, Q192R, on platelet inhibition in response to clopidogrel remains controversial. We aimed to investigate the association between carrier status of PON1 Q192R and high platelet reactivity (HPR) with clopidogrel in patients undergoing elective neurointervention.

Methods: Post-clopidogrel platelet reactivity was measured using a VerifyNow® P2Y12 assay in P2Y12 reaction units (PRU) for consecutive patients before the treatment. Genotype testing was performed for PON1 Q192R and CYP2C19*2 and *3 (no function alleles), and *17. PRU was corrected on the basis of hematocrit. We investigated associations between factors including carrying ≥1 PON1 192R allele and HPR defined as original and corrected PRU ≥208.

Results: Of 475 patients (232 men, median age, 68 years), HPR by original and corrected PRU was observed in 259 and 199 patients (54.5% and 41.9%), respectively. Carriers of ≥1 PON1 192R allele more frequently had HPR by original and corrected PRU compared with non-carriers (91.5% vs 85.2%, P = 0.031 and 92.5% vs 85.9%, P = 0.026, respectively). In multivariate analyses, carrying ≥1 PON1 192R allele was associated with HPR by original (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.03-3.76) and corrected PRU (OR 2.34, 95% CI 1.21-4.74) after adjustment for age, sex, treatment with antihypertensive medications, hematocrit, platelet count, total cholesterol, and carrying ≥1 CYP2C19 no function allele.

Conclusions: Carrying ≥1 PON1 192R allele is associated with HPR by original and corrected PRU with clopidogrel in patients undergoing elective neurointervention, although alternative results related to other genetic polymorphisms cannot be excluded.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254067PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341610PMC
August 2021

Circulating immune- and inflammation-related biomarkers and early-stage noncardia gastric cancer risk.

Eur J Cancer Prev 2021 Jul 8. Epub 2021 Jul 8.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA Division of Cancer Information and Control Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Aichi Cancer Center Research Institute Department of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background: In Helicobacter pylori-driven gastric cancer, mucosal colonization induces chronic inflammation that may variably progress to cancer. Prospective studies of circulating inflammation-related proteins have suggested weak associations with gastric cancer risk. To assess potential utility as a screening tool in clinical settings, we examined circulating levels of a wide range of key inflammation molecules for associations with early-stage gastric cancer.

Methods: We used pretreatment EDTA plasma from 239 individuals with early-stage noncardia gastric cancer (203 stage I and 36 stage II) and 256 age-frequency-matched H. pylori-seropositive cancer-free controls within the Hospital-based Epidemiologic Research Program at Aichi Cancer Center. Levels of 92 biomarkers were measured by proximity extension assays using Olink's Proseek Immuno-oncology Panel. Odds ratios (ORs) for association with gastric cancer risk were calculated for quantiles (two to four categories) of each biomarker from unconditional logistic regression models, adjusted for age, sex, smoking and alcohol consumption. Two-sided P values <0.05 were considered as significant. The false discovery rate (FDR) was used to correct for multiple comparisons.

Results: Of 83 evaluable biomarkers, lower levels of TNFRSF12A (per quartile OR, 0.82; nominal P-trend = 0.02) and ADGRG1 (per quartile OR, 0.84; nominal P-trend = 0.03) were associated with early-stage gastric cancer but were not statistically significant after FDR correction.

Conclusion: Our study did not identify any inflammation-related biomarkers that may be useful for early disease detection. To date, this is the first assessment of circulating inflammation-related proteins in early-stage gastric cancer. Given the complex inflammation processes preceding malignant transformation, further investigation of other biomarkers is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CEJ.0000000000000706DOI Listing
July 2021

Survival benefit of surgery for very elderly patients with pancreatic cancer: what extent of pancreatectomy is acceptable?

Nagoya J Med Sci 2021 May;83(2):239-250

Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan.

The purpose of this study is to clarify the survival benefit and acceptable extent of surgery for very elderly patients with pancreatic cancer. Patients (n=55) ≥80 years with resectable pancreatic cancer were studied. 29 underwent pancreatectomy, 16 underwent chemotherapy, and 10 received best supportive care. Uni and multivariate analysis were performed to explore predictive factors for overall survival (OS) with surgery and chemotherapy (n=45). Postoperative survival of PD (pancreatoduodenectomy) and DP (distal pancreatectomy) and of PD-PVR (PD with portal vein resection) and PD were compared. OS was equivalent with surgery and chemotherapy (median survival time [MST]; 685 vs. 626 days, respectively; p=0.057); 6 patients surivived ≥3 years after surgery. Pancreatectomy was not a prognostic factor. Survival was significantly worse with PD-PVR than with PD, but equivalent with PD and DP. Within 2 years after PD-PVR, 8 patients have died. Surgery was not a positive prognostic factor for very elderly patients with pancreatic cancer, but was the sole chance for survival ≥3 years. Indication for PD-PVR for very elderly patients should be determined more cautiously compared with that for non-elderly patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18999/nagjms.83.2.239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236693PMC
May 2021

[Aldehyde degradation deficiency (ADD) syndrome: discovery of a novel fanconi anemia-like inherited BMF syndrome due to combined ADH5/ALDH2 deficiency].

Rinsho Ketsueki 2021 ;62(6):547-553

Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Graduate School of Biostudies, Kyoto University.

We have recently described the identification of a novel inherited bone marrow failure syndrome. The first set of patients was diagnosed through the exome analysis of cells from Japanese patients with hypoplastic anemia, which have been deposited to the JCRB cell bank for quite some time previously. Originally, these cases were diagnosed with a novel disorder based on increased levels of sister chromatid exchanges in lymphocytes; however, causative genes were clarified only after applying the recently developed next-generation sequencing technology. Aldehyde degradation deficiency syndrome (ADDS) is caused by combined defects in two genes, ADH5 and ALDH2, which are both critical for degrading endogenously generated formaldehyde. Formaldehyde is highly reactive and toxic to biological molecules including DNA, and its endogenous generation in the absence of the degradation system results in DNA damage that overwhelms the DNA repair capacity, leading to the development of BMF with loss of hematopoietic stem cells and progression to MDS/leukemia. In this short review, we would like to summarize what is known today about ADDS for a wide readership of hematology clinicians in Japan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11406/rinketsu.62.547DOI Listing
July 2021

Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element.

Am J Hum Genet 2021 07 18;108(7):1190-1203. Epub 2021 Jun 18.

Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.

A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 × 10).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajhg.2021.05.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322933PMC
July 2021

Associations of circulating mediators of inflammation, cell regulation and immune response with esophageal squamous cell carcinoma.

J Cancer Res Clin Oncol 2021 Oct 14;147(10):2885-2892. Epub 2021 Jun 14.

Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.

Background: Esophageal squamous cell carcinoma (ESCC) is the most common histologic subtype of esophageal cancer globally. The development of squamous cell carcinoma has important inflammatory influences and effects. We, therefore, examined circulating levels of inflammation- and immune-related proteins for associations with ESCC.

Methods: We used pre-treatment EDTA plasma from 80 ESCC patients (44% clinical stages I and II) and 80 cancer-free control individuals within the Hospital-based Epidemiologic Research Program at Aichi Cancer Center. Levels of 184 biomarkers were measured by high-throughput multiplexed proximity extension assays using Olink's Proseek Cell Regulation and Immuno-Oncology Panels. ESCC odds ratios (OR) per quantile (based on two to four categories) of each biomarker were calculated by unconditional logistic regression models, adjusted for age, sex, cigarette smoking and alcohol consumption. Correlations among continuous biomarker levels were assessed by Spearman's rank correlation. All statistical tests were two-sided with p values < 0.05 considered as significant. Given the exploratory nature of the study, we did not adjust for multiple comparisons.

Results: Seven proteins were undetectable in nearly all samples. Of the remaining 177 evaluable biomarkers, levels of cluster of differentiation 40 (CD40, per quartile OR 1.64; p trend = 0.018), syntaxin 16 (STX16, per quartile OR 1.63; p trend = 0.008), heme oxygenase 1 (per quartile OR 1.59; p trend = 0.014), and γ-secretase activating protein (GSAP, per quartile OR 1.47; p trend = 0.036) were significantly associated with ESCC. Amongst these significant markers, levels of CD40, STX16, and GSPA were moderately correlated (Rho coefficients 0.46-0.55; p < 0.05).

Conclusion: Our case-control study expands the range of inflammation and immune molecules associated with ESCC. These novel findings warrant replication and functional characterization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00432-021-03687-3DOI Listing
October 2021

Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?

Cancers (Basel) 2021 May 14;13(10). Epub 2021 May 14.

Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark.

In this study we aim to examine gene-environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (-2df = 1.2 × 10). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (-2df = 1.1 × 10). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13102370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156547PMC
May 2021

Reduction in total and major cause-specific mortality from tobacco smoking cessation: a pooled analysis of 16 population-based cohort studies in Asia.

Int J Epidemiol 2021 Feb 5. Epub 2021 Feb 5.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Little is known about the time course of mortality reduction following smoking cessation in Asians who have smoking behaviours distinct from their Western counterparts. We evaluated the level of reduction in all-cause, cardiovascular disease (CVD) and lung cancer mortality by years since quitting smoking, in Asia.

Methods: Using Cox regression, we analysed individual participant data (n = 709 151) from 16 prospective cohorts conducted in China, Japan, Korea/Singapore, and India/Bangladesh, separately by cohorts. Cohort-specific hazard ratios (HRs) were combined using a random-effects meta-analysis.

Results: During a mean follow-up of 12.0 years, 108 287 deaths were ascertained-35 658 from CVD and 7546 from lung cancer. Among Asian men, a dose-response relationship of risk reduction in deaths from all causes, CVD and lung cancer was observed with an increase in years after smoking cessation. Compared with never smokers, however, all-cause and CVD mortality among former smokers remained elevated 10-14 years after quitting [multivariable-adjusted HR (95% confidence interval (CI) = 1.25 (1.13-1.37) and 1.20 (1.02-1.41), respectively]. Lung cancer mortality stayed almost 2-fold higher than among never smokers 15-19 years after smoking cessation [1.97 (1.41-2.73)], particularly among former heavy smokers [2.62 (1.71-4.00)]. Women who quitted for ≥5 years retained a significantly elevated mortality from all causes, CVD and lung cancer. Overall patterns of the cessation-mortality associations were similar across countries.

Conclusions: Our findings suggest that adverse effects of tobacco smoking persist for an extended time period, even for more than two decades, which is beyond the time windows defined in current clinical guidelines for risk assessment of lung cancer and CVD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ije/dyab087DOI Listing
February 2021

Impact of the combination of donor age and HLA disparity on the outcomes of unrelated bone marrow transplantation.

Bone Marrow Transplant 2021 10 14;56(10):2410-2422. Epub 2021 May 14.

Department of Hematology and Oncology, Kyoto University, Kyoto, Japan.

Impact of donor age considering HLA disparity on hematopoietic cell transplantation (HCT) outcomes has not been fully evaluated. We evaluated 8486 patients who received unrelated bone marrow transplantation (UR-BMT) from 8/8 or 7/8 HLA-matched donors. Compared to 8/8 HLA-matched younger donors (<40 years), 8/8 HLA-matched older donors (subdistribution hazard ratio [SHR], 1.16; 95% CI, 0.97-1.38) and 7/8 HLA-matched younger donors (SHR, 1.33; 95% CI, 1.11-1.58) were associated with increased risk of grade III-IV acute graft-versus-host disease (aGVHD). 7/8 HLA-matched older donors had further increased risk (SHR, 2.00; 95% CI, 1.68-2.38) due to interaction between donor age and HLA disparity (p for interaction = 0.038). Progression-free survival (PFS) after UR-BMT with 8/8 HLA-matched younger donors was comparable to that after UR-BMT with 8/8 HLA-matched older donors, whereas UR-BMT with 7/8 HLA-matched younger or older donors was significantly associated with lower PFS than UR-BMT with 8/8 HLA-matched younger donors (younger donor; HR, 1.12; 95% CI, 1.04-1.21, older donor; HR, 1.28; 95% CI, 1.17-1.40; p for interaction = 0.079). In conclusion, adverse effect of increased donor age requires attention, especially in HLA-mismatched UR-BMT due to interaction between donor age and HLA disparity. Intensive aGVHD prophylaxis may be required to improve outcomes after HCT with mismatched older donors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41409-021-01289-8DOI Listing
October 2021

Continuous suture is a risk factor for benign hepaticojejunostomy stenosis after pancreatoduodenectomy in patients with a non-dilated bile duct.

HPB (Oxford) 2021 Apr 27. Epub 2021 Apr 27.

Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Kanokoden 1-1, Chikusa-ku, Nagoya, Japan.

Background: It is unclear whether hepaticojejunostomy with a continuous suture is suitable for patients with a non-dilated bile duct.

Methods: Medical records of patients who underwent pancreatoduodenectomy between 2003 and 2013 were retrospectively reviewed, focusing on the incidence of benign anastomotic stenosis and its relationship with suture method (continuous vs interrupted) and common hepatic duct size.

Results: Among 336 patients, 172 had a non-dilated (<8 mm) duct, and the remaining 164 had a dilated duct. Benign stenosis occurred in 12.2% (21/172) in the former, but in only 0.6% (1/164) in the latter (p < 0.001; median follow-up period, 43.5 months). Thus, further analysis was conducted in the 172 patients with a non-dilated duct, among whom 116 received a continuous suture and 56 received an interrupted suture. The cumulative incidence of benign anastomotic stenosis was significantly higher in patients who received a continuous suture vs those who received an interrupted suture (15.6% vs 1.8%, respectively, at 3 years; p = 0.006). Multivariable analysis identified continuous suture, male gender, and cholangitis (within 3 months after surgery) as independent risk factors for benign stenosis.

Conclusions: In this observational study, the use of a continuous suture was associated with benign anastomotic stricture in patients with a non-dilated hepatic duct.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hpb.2021.04.010DOI Listing
April 2021

Transarterial Embolization for Bleeding in Patients with Head and Neck Cancer: Who Benefits?

Laryngoscope 2021 Nov 7;131(11):E2777-E2783. Epub 2021 May 7.

Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.

Objectives/hypothesis: The present study aimed to investigate the efficacy of transarterial embolization (TAE) for bleeding in patients with head and neck cancer (HNC) and to evaluate the prognostic factors after TAE.

Study Design: Outcome study.

Methods: This retrospective study included 31 consecutive patients (27 men and 4 women; median age, 61 years) who presented uncontrollable hemorrhage associated with HNC and underwent emergency TAE at our institution during a 10-year period (January 2011-December 2020). This corresponded to 40 TAE procedures, including 27 cases with an unstable status (circulatory and/or respiratory insufficiency) and 10 cases with carotid blowout syndrome. The technical success rate and adverse events were analyzed on a per-procedure basis. The rebleeding and overall survival (OS) rates were analyzed on a per-patient basis, and the factors related to OS were evaluated.

Results: The technical success rate was 100%. As an adverse event, cerebral infarction was found in three cases with carotid blowout syndrome. The rebleeding rate at 30 days after TAE and in the follow-up period (range, 9-3,004 days) was 17.2% and 35.5%, respectively. The median survival time was 263 days (95% confidence interval: 124.0-402.0 days). In the log-rank test, complete remission (CR) of the primary cancer at the time of the first TAE was identified as a significant influencing factor of survival.

Conclusion: TAE is effective for the treatment of hemorrhage associated with HNC even in patients with an unstable status. Patients with CR can gain a long life span.

Level Of Evidence: 4 Laryngoscope, 131:E2777-E2783, 2021.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lary.29611DOI Listing
November 2021

Randomized phase II study of daily and alternate-day administration of S-1 for adjuvant chemotherapy in completely-resected stage I non-small cell lung cancer: results of the Setouchi Lung Cancer Group Study 1301.

BMC Cancer 2021 May 6;21(1):506. Epub 2021 May 6.

Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kita-ku, Okayama, Japan.

Background: The aim of this multicenter, randomized phase II study was to analyze the feasibility and safety of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in patients with completely resected pathological stage I (tumor diameter > 2 cm) non-small cell lung cancer (NSCLC).

Methods: Patients were randomly assigned to receive adjuvant chemotherapy for 1 year comprising either alternate-day oral administration of S-1 (80 mg/m/day) for 4 days a week (Group A) or a 2-week oral administration of S-1 (80 mg/m/day) followed by 1 week of rest (Group B). The primary endpoint was feasibility, which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more.

Results: Ninety-three patients were enrolled of whom 90 patients received S-1 treatment. Median follow-up was 66.9 months. The treatment completion rate based on an RDI of 70% or more for 6 months was 84.4% (95%CI; 70.5-93.5%) in group A and 64.4% (95%CI; 48.8-78.1%) in group B. There were no grade 4 adverse events in either group. Moderate or severe adverse events (grade 2 or grade 3) were significantly more frequent in group B (67%) compared with group A (29%, P = 0.001). The 5-year relapse-free survival rate was 87.0 and 80.9% for group A and B, respectively (P = 0.451). The 5-year overall survival rate for all patients (n = 93) was 100 and 89.4% for group A and B, respectively (P = 0.136).

Conclusion: Alternate-day oral administration of S-1 for 1 year as adjuvant chemotherapy was demonstrated to be feasible with low toxicity in completely resected stage I (tumor diameter > 2 cm) NSCLC.

Trial Registration: Trial registration number: UMIN000011994 . Date of registration: 10/8/2013.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-021-08232-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101150PMC
May 2021

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

Jpn J Clin Oncol 2021 Jul;51(7):1158-1170

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jjco/hyab055DOI Listing
July 2021

Neck Dissections Based on Sentinel Lymph Node Navigation Versus Elective Neck Dissections in Early Oral Cancers: A Randomized, Multicenter, and Noninferiority Trial.

J Clin Oncol 2021 Jun 20;39(18):2025-2036. Epub 2021 Apr 20.

National Cancer Center Hospital, Tokyo, Japan.

Purpose: This study aimed to compare patients with early oral cavity squamous cell carcinoma (OCSCC) (tumor category [T] 1-2, node-negative, and no distant metastasis) treated with traditional elective neck dissection (ND) with those managed by sentinel lymph node biopsy (SLNB) using survival and neck function and complications as end points.

Methods: Sixteen institutions in Japan participated in the study (trial registration number: UMIN000006510). Patients of age ≥ 18 years with histologically confirmed, previously untreated OCSCC (Union for International Cancer Control TNM Classification of Malignant Tumors 7th edition T1-2, node-negative no distant metastasis), with ≥ 4 mm (T1) depth of invasion, were randomly assigned to undergo standard selective ND (ND group; n = 137) or SLNB-navigated ND (SLNB group; n = 134). The primary end point was the 3-year overall survival rate, with a 12% noninferiority margin; secondary end points included postoperative neck functionality and complications and 3-year disease-free survival. Sentinel lymph nodes underwent intraoperative multislice frozen section analyses for the diagnosis. Patients with positive sentinel lymph nodes underwent either one-stage or second-look ND.

Results: Pathologic metastasis-positive nodes were observed in 24.8% (34 of 137) and 33.6% (46 of 134) of patients in the ND and SLNB groups, respectively ( = .190). The 3-year overall survival in the SLNB group (87.9%; lower limit of one-sided 95% CI, 82.4) was noninferior to that in the ND group (86.6%; lower limit 95% CI, 80.9; for noninferiority < .001). The 3-year disease-free survival rate was 78.7% (lower limit 95% CI, 72.1) and 81.3% (75.0) in the SLNB and ND groups, respectively ( for noninferiority < .001). The scores of neck functionality in the SLNB group were significantly better than those in the ND group.

Conclusion: SLNB-navigated ND may replace elective ND without a survival disadvantage and reduce postoperative neck disability in patients with early-stage OCSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.20.03637DOI Listing
June 2021

Clopidogrel response predicts thromboembolic events associated with coil embolization of unruptured intracranial aneurysms: A prospective cohort study.

PLoS One 2021 8;16(4):e0249766. Epub 2021 Apr 8.

Department of Neurology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Objective: Periprocedural thromboembolic events are a serious complication associated with coil embolization of unruptured intracranial aneurysms. However, no established clinical rule for predicting thromboembolic events exists. This study aimed to clarify the significance of adding preoperative clopidogrel response value to clinical factors when predicting the occurrence of thromboembolic events during/after coil embolization and to develop a nomogram for thromboembolic event prediction.

Methods: In this prospective, single-center, cohort study, we included 345 patients undergoing elective coil embolization for unruptured intracranial aneurysm. Thromboembolic event was defined as the occurrence of intra-procedural thrombus formation and postprocedural symptomatic cerebral infarction within 7 days. We evaluated preoperative clopidogrel response and patients' clinical information. We developed a patient-clinical-information model for thromboembolic event using multivariate analysis and compared its efficiency with that of patient-clinical-information plus preoperative clopidogrel response model. The predictive performances of the two models were assessed using area under the receiver-operating characteristic curve (AUC-ROC) with bootstrap method and compared using net reclassification improvement (NRI) and integrated discrimination improvement (IDI).

Results: Twenty-eight patients experienced thromboembolic events. The clinical model included age, aneurysm location, aneurysm dome and neck size, and treatment technique. AUC-ROC for the clinical model improved from 0.707 to 0.779 after adding the clopidogrel response value. Significant intergroup differences were noted in NRI (0.617, 95% CI: 0.247-0.987, p < .001) and IDI (0.068, 95% CI: 0.021-0.116, p = .005).

Conclusions: Evaluation of preoperative clopidogrel response in addition to clinical variables improves the prediction accuracy of thromboembolic event occurrence during/after coil embolization of unruptured intracranial aneurysm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249766PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8031457PMC
September 2021
-->