Importance of circulating leptin and adiponectin in the causal pathways between obesity and the development of colorectal cancer in Japanese men.

BACKGROUND: The mechanistic associations between obesity and risk of colorectal cancer (CRC) remain unclear. Here, using body mass index (BMI) as an obesity indicator, we decomposed the total effects of obesity on the risk of CRC into: (1) direct effects, which are possibly mediated by unmeasured or currently unknown factors; (2) indirect effects mediated by circulating leptin and adiponectin; and (3) indirect effects that are not mediated by circulating leptin and adiponectin but by hyperinsulinemia and chronic inflammation (assessed via circulating connecting peptide and C-reactive protein, respectively). METHODS: We adopted a causal mediation framework, using data from a large prospective cohort study of 44,271 Japanese men. RESULTS: BMI was not associated with the risk of CRC due to direct and indirect effects that were not mediated by circulating leptin and adiponectin. By contrast, individuals with BMIs of 25.0-27.4 kg/m2 (risk ratio, 1.29; 95% confidence interval, 0.98-1.69) and ≥27.5 kg/m2 (risk ratio, 1.28; 95% confidence interval, 0.98-1.68) had a higher risk of CRC due to indirect effects of circulating leptin and adiponectin. CONCLUSIONS: Our mediation analyses suggest that the association between BMI and CRC risk may be largely mediated by a pathway involving circulating leptin and adiponectin.

Patients' perceptions of patient-centered communication with healthcare providers and associated factors in Japan - The INFORM Study 2020.

OBJECTIVE: To describe patients' perceptions of the patient-centeredness of their communication with healthcare providers in Japan, and to examine factors associated with these perceptions. METHODS: We analyzed the cross-sectional data from the INFORM Study 2020, which is a nationwide survey on health information access in Japan. A total of 3605 respondents completed the survey. Our primary outcome was the nine elements of the patient-centered communication scale (PCCS), which was compiled from 2703 respondents (75.0%) reporting at least one provider visit within 12 months. It was rated on a four-point Likert scale: always, usually, sometimes, and never. We used binary logistic regression to examine the association between sociodemographic and health-related variables, and each element of the PCCS. RESULTS: For all elements, the percentage of respondents who agreed that their healthcare providers always communicated in a patient-centered way was low (17-31%). Patients with higher age, higher education, poorer general health status and a larger number of visits to providers in the previous 12 months were more likely to have positive perception. CONCLUSION: Patient-centered communication as reported in a national sample in Japan was low. CLINICAL IMPLICATIONS: Efforts are needed to improve the patient-centeredness of patient-provider communication in Japan to optimize health outcomes.

Associations of individual characteristics and socioeconomic status with heated tobacco product harmfulness perceptions in Japan: A nationwide cross-sectional study (INFORM Study 2020).

IntroductionIn Japan, heated tobacco products (HTPs) are promoted by the tobacco industry as reduced-risk tobacco products despite the lack of evidence for this claim. This study determined the distribution of HTP-harmfulness perception and identify the explanatory factors associated with the perception of HTP as less harmful than conventional cigarettes.MethodsA nationwide cross-sectional survey was conducted with Japanese people aged 20 years or older (INFORM Study 2020) using a self-administered questionnaire. We performed descriptive analysis and weighted logistic regression analysis to examine the relationship between explanatory factors (e.g., individual characteristics, socioeconomic status, and trusted sources of cancer information) and the perception of HTPs as less harmful.ResultsAmong 3,420 participants (response rate: 35.2%), the proportions of those who perceived HTPs as less harmful were 40.3% and 18.3% for users and non-users of tobacco, respectively. For participants aged 20-39 years, the proportion were 49.9% and 30.4%, respectively. Among 1,160 non-tobacco users who were familiar with HTPs, male, aged under 39 years, and had lower education were associated with the perception of HTPs as less harmful. Trusted sources of cancer information were not associated with the perception of HTPs as less harmful.ConclusionsThis study showed that, among non-tobacco users, being male, aged under 39 years, and lower education were associated with a perception of HTPs as less harmful. Public health stakeholders should provide the latest evidence about HTP harmfulness in their daily practice, and strengthen the regulations on HTP marketing directed at both tobacco- and non-tobacco users.

Short-term effectiveness and safety of rituximab versus cyclophosphamide for life-threatening ANCA-associated vasculitis: a propensity score analysis of the real-world nationwide database.

OBJECTIVES: Life-threatening antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with rapidly progressive glomerulonephritis (RPGN) and/or alveolar haemorrhage (AH) has a poor prognosis. Rituximab (RTX) is as effective as cyclophosphamide (CY) in remission induction therapy; however, the effectiveness and safety of RTX have not been established in life-threatening AAV. This study aimed to investigate the short-term effectiveness and safety of RTX in life-threatening AAV with RPGN and/or AH. METHODS: Between April 2018 and March 2020, cases treated with systemic glucocorticoids and RTX or intravenous CY (IVCY) was extracted from a Japanese nationwide inpatient database. Effectiveness was evaluated by in-hospital mortality and severe renal dysfunction requiring haemodialysis (HD) at discharge. Safety was evaluated by the in-hospital incidence of infections. The propensity score (PS) for RTX was estimated. Multivariable Cox and logistic regression with adjustment for PS were conducted to estimate the association of RTX with outcomes. RESULTS: From 16 001 612 hospitalised records, 687 life-threatening AAV cases were extracted. No significant difference in in-hospital mortality (adjusted HR 1.06; 95% CI 0.62 to 1.80) was found between the groups. Although the RTX group had a lower risk of fungal infections (adjusted OR (aOR) 0.45; 95% CI 0.23 to 0.84) and pneumocystis pneumonia (aOR 0.58; 95% CI 0.32 to 1.00), they might have an increased risk of severe renal dysfunction requiring HD at discharge (aOR 2.58; 95% CI 1.02 to 6.91). CONCLUSIONS: In life-threatening AAV, RTX has similar short-term effectiveness on mortality to IVCY. Although RTX might have a lower risk of fungal infections and pneumocystis pneumonia, the short-term renal prognosis might be inferior to IVCY.

Trust in Mass Media as Sources of Cancer Information: Findings from a Nationally Representative Cross-Sectional Survey in Japan.

Trust is a major factor in effective public dissemination and use of relevant health information to guide important health decisions. To examine mass media as a communication channel for delivering cancer information among Japanese adults, we identified the level of trust in various types of mass media as sources of cancer information, and examined factors associated with trust, including exposure to mass media, sociodemographic factors, and cancer history. Data were analyzed for 3,109 Japanese adults who responded to a nationally representative cross-sectional mail survey. Data included trust in cancer information sources, sociodemographic variables, cancer history, and exposure to mass media. Logistic regression analysis was used. The prevalence of high trust in cancer information sources was highest for physicians (94.7%). Among mass media, Internet (47.2%) was the most trusted source of cancer-related information, followed by television (44.3%), newspapers/magazines (42.7%), and radio (32.7%). The high-exposure group for newspapers (AOR = 1.28, 95%CI = 1.07-1.54) was more likely to trust newspapers. Similarly, high-exposure groups for radio (1.22, 1.02-1.45), Internet (1.21, 1.01-1.45), and television (1.30, 1.10-1.53) were positively associated with trust in each media type. Although trust in mass media was lower than trust in physicians, the study found that a large group of respondents had high levels of trust in mass media sources. Trust in cancer information from each mass media type was mainly related to the level of exposure to each mass media type. Developing health communication strategies using mass media may be effective for disseminating relevant cancer information in Japan.

Age, gender and socioeconomic disparities in human papillomavirus (HPV) awareness and knowledge among Japanese adults after a 7-year suspension of proactive recommendation for the HPV vaccine: A nationally representative cross-sectional survey.

The Japanese government's 2013 suspension of its proactive recommendation for Human papillomavirus (HPV) vaccination resulted in low HPV vaccination coverage and was unique. However, data on awareness and knowledge of HPV vaccines in the general population was limited. Here, to investigate more recent awareness and knowledge of HPV vaccines by age, gender, and socioeconomic status, we used data from the INFORM Study 2020, a nationally representative cross-sectional survey of self-administered questionnaires with 1,998 Japanese individuals aged 20 to 59 years. We found that 47.5% of females and 21.0% of males had heard of HPV, and 33.6% of females and 16.8% of males had knowledge of HPV vaccine efficacy. After adjusting for potential confounders, females aged 50-54 years were more likely to be aware of HPV than females aged 20-24 (AOR, 2.02, 95%CI: 1.12-3.65). Females (AOR, 2.13, 95%CI: 1.48-3.07) and males (AOR, 1.64, 95%CI: 1.03-2.59) with higher education had more awareness than those with less education. Females with higher education had more knowledge about HPV vaccine efficacy than those with less education (AOR, 1.70; 95%CI: 1.16-2.50). We found a generally low level of awareness and knowledge about HPV vaccines in Japan, which might be attributable to the suspension of proactive recommendations. Additionally, we identified disparities in awareness and knowledge by age, gender, socioeconomic status, and health literacy. Enhancing HPV awareness and understanding of HPV vaccines and implementing targeted efforts for specific subpopulations within Japan after the resumption of proactive recommendation for HPV vaccines, are imperative.

Hypothesis testing procedure for binary and multi-class F1 -scores in the paired design.

In modern medicine, medical tests are used for various purposes including diagnosis, disease screening, prognosis, and risk prediction. To quantify the performance of the binary medical test, we often use sensitivity, specificity, and negative and positive predictive values as measures. Additionally, the F 1 $$ {F}_1 $$ -score, which is defined as the harmonic mean of precision (positive predictive value) and recall (sensitivity), has come to be used in the medical field due to its favorable characteristics. The F 1 $$ {F}_1 $$ -score has been extended for multi-class classification, and two types of F 1 $$ {F}_1 $$ -scores have been proposed for multi-class classification: a micro-averaged F 1 $$ {F}_1 $$ -score and a macro-averaged F 1 $$ {F}_1 $$ -score. The micro-averaged F 1 $$ {F}_1 $$ -score pools per-sample classifications across classes and then calculates the overall F 1 $$ {F}_1 $$ -score, whereas the macro-averaged F 1 $$ {F}_1 $$ -score computes an arithmetic mean of the F 1 $$ {F}_1 $$ -scores for each class. Additionally, Sokolova and Lapalme 1 $$ {}^1 $$ gave an alternative definition of the macro-averaged F 1 $$ {F}_1 $$ -score as the harmonic mean of the arithmetic means of the precision and recall over classes. Although some statistical methods of inference for binary and multi-class F 1 $$ {F}_1 $$ -scores have been proposed, the methodology development of hypothesis testing procedure for them has not been fully progressing yet. Therefore, we aim to develop hypothesis testing procedure for comparing two F 1 $$ {F}_1 $$ -scores in paired study design based on the large sample multivariate central limit theorem.

Interactive assistance via eHealth for small- and medium-sized enterprises' employer and health care manager teams on tobacco control (eSMART-TC): protocol for a cluster randomized hybrid type II trial (N-EQUITY2101/J-SUPPORT2102).

BACKGROUND: Tobacco control should be a higher public health priority in Japan. Some workplaces provide smoking cessation support and connect employees to effective smoking cessation treatments such as outpatient clinics. However, tobacco control measures have not been sufficiently implemented in Japan, especially in small- and medium-sized enterprises (SMEs), where resources are limited. Organizational commitment and consistent leadership are crucial to facilitate implementation, but research on whether supporting organizational leaders leads to health behavior changes among employees is limited. METHODS: This hybrid type II cluster randomized effectiveness implementation trial (eSMART-TC) aims to examine the effects of interactive assistance for SME management on health and implementation outcomes. We will provide interactive assistance to employers and health managers for 6 months, aiming to promote the utilization of reimbursed smoking cessation treatments by public health insurance and to implement smoke-free workplaces. The intervention will consist of three strategies: supporting employees through campaigns, tailored ongoing facilitation, and ensuring executive engagement and support. The primary health and implementation outcomes will be salivary cotinine-validated 7-day point-prevalence abstinence rate, and the adoption of two recommended measures (promoting utilization of smoking cessation treatment and implementing smoke-free workplaces) 6 months after the initial session, respectively. Other outcomes for implementation (e.g., penetration of smoking cessation clinic visits), health (e.g., salivary cotinine-validated 7-day point-prevalence abstinence rate at 12 months), and process (e.g., adherence and potential moderating factors) will be collected via questionnaires, interviews, logbooks, and interventionists' notes at 6 and 12 months. An economic analysis will be undertaken to assess the cost-effectiveness of the implementation interventions at 12 months. DISCUSSION: This will be the first cluster randomized controlled trial to evaluate the effectiveness of an implementation intervention with interactive assistance for employers and health managers in SMEs on smoking cessation and implementation of evidence-based tobacco control measures in SMEs. The findings of this trial targeting management in SMEs have the potential to accelerate the implementation of evidence-based smoking cessation methods as well as abstinence rates among employees in SMEs across Japan. TRIAL REGISTRATION: The study protocol has been registered in the UMIN Clinical Trials Registry (UMIN-CTR; ID: UMIN000044526). Registered on 06/14/2021.

Lack of significant associations between single nucleotide polymorphisms in LPAL2-LPA genetic region and all cancer incidence and mortality in Japanese population: The Japan public health center-based prospective study.

BACKGROUND: High lipoprotein (a) level is an established cardiovascular risk, but its association with non-cardiovascular diseases, especially cancer, is controversial. Serum lipoprotein (a) levels vary widely by genetic backgrounds and are largely determined by the genetic variations of apolipoprotein (a) gene, LPA. In this study, we investigate the association between SNPs in LPA region and cancer incidence and mortality in Japanese. METHODS: A genetic cohort study was conducted utilizing the data from 9923 participants in the Japan Public Health Center-based Prospective Study (JPHC Study). Twenty-five SNPs in the LPAL2-LPA region were selected from the genome-wide genotyped data. Cox regression analysis adjusted for the covariates and competing risks of death from other causes, were used to estimate the relative risk (hazard ratios (HR) with 95% confidence intervals (CI)) of overall and site-specific cancer incidence and mortality, for each SNP. RESULTS: No significant association was found between SNPs in the LPAL2-LPA region and cancer incidence or mortality (overall/site-specific cancer). In men, however, HRs for stomach cancer incidence of 18SNPs were estimated higher than 1.5 (e.g., 2.15 for rs13202636, model free, 95%CI: 1.28-3.62) and those for stomach cancer mortality of 2SNPs (rs9365171, rs1367211) were estimated 2.13 (recessive, 95%CI:1.04-4.37) and 1.61 (additive, 95%CI: 1.00-2.59). Additionally, the minor allele for SNP rs3798220 showed increased death risk from colorectal cancer (CRC) in men (HR: 3.29, 95% CI:1.59 - 6.81) and decreased CRC incidence risk in women (HR: 0.46, 95%CI: 0.22-0.94). Minor allele carrier of any of 4SNPs could have risk of prostate cancer incidence (e.g., rs9365171 dominant, HR: 1.71, 95%CI: 1.06-2.77). CONCLUSIONS: None of the 25 SNPs in the LPAL2-LPA region was found to be significantly associated with cancer incidence or mortality. Considering the possible association between SNPs in LPAL2-LPA region and colorectal, prostate and stomach cancer incidence or mortality, further analysis using different cohorts is warranted.

Smoking and risk of colorectal cancer according to KRAS and BRAF mutation status in a Japanese prospective Study.

Although smoking is a major modifiable risk factor for many types of cancer, evidence for colorectal cancer is equivocal in Asian populations. Recent Western studies have proposed that the association between smoking and colorectal cancer is restricted to specific tumor molecular subtypes. However, no studies have evaluated the association according to tumor molecular subtypes in Asian populations. In a Japanese prospective population-based cohort study of 18 773 participants, we collected tumor tissues from incident colorectal cancer cases and evaluated KRAS (Kirsten rat sarcoma viral oncogene homolog) and BRAF (v-raf murine sarcoma viral oncogene homolog B) mutation status using target sequencing. Multivariable-adjusted Cox proportional hazard model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of smoking with the risk of overall colorectal cancer and its subtypes defined by KRAS and BRAF mutation status. Among 339 cases, KRAS and BRAF mutations were identified in 164 (48.4%) and 16 (4.7%) cases, respectively. The multivariable-adjusted HR for ever smoking compared with never smoking was 1.24 [95% CI: 0.93-1.66], 1.75 [1.14-2.68], 0.87 [0.59-1.29], 1.24 [0.93-1.67] and 1.22 [0.38-3.93] for overall, KRAS wild-type, KRAS-mutated, BRAF wild-type and BRAF-mutated colorectal cancer, respectively. The statistically significant heterogeneity was indicated between KRAS mutation status (Pheterogeneity = 0.01) but not between BRAF mutation status. This study is the first to demonstrate that smokers have an approximately 2-fold higher risk of KRAS wild-type colorectal cancer than never smokers in an Asian population. Our findings support that smoking is a risk factor for colorectal cancer, especially for its subtype without KRAS mutations, in Asian populations.

Genomic landscape and its prognostic significance in stage III colorectal cancer: JCOG1506A1, an ancillary of JCOG0910.

Large-scale genomic sequencing of colorectal cancers has been reported mainly for Western populations. Differences by stage and ethnicity in the genomic landscape and their prognostic impact remain poorly understood. We investigated 534 Japanese stage III colorectal cancer samples from the Phase III trial, JCOG0910. Targeted-capture sequencing of 171 potentially colorectal cancer-associated genes was performed, and somatic single-nucleotide variants and insertion-deletions were determined. Hypermutated tumors were defined as tumors with MSIsensor score >7 and ultra-mutated tumors with POLE mutations. Genes with alterations associated with relapse-free survival were analyzed using multivariable Cox regression models. In all patients (184 right-sided, 350 left-sided), mutation frequencies were TP53, 75.3%; APC, 75.1%; KRAS, 43.6%; PIK3CA, 19.7%; FBXW7, 18.5%; SOX9, 11.8%; COL6A3, 8.2%; NOTCH3, 4.5%; NRAS, 4.1%; and RNF43, 3.7%. Thirty-one tumors were hypermutated (5.8%; 14.1% right-sided, 1.4% left-sided). Modest associations were observed: poorer relapse-free survival was seen with mutant KRAS (hazard ratio 1.66; p = 0.011) and mutant RNF43 (2.17; p = 0.055), whereas better relapse-free survival was seen with mutant COL6A3 (0.35; p = 0.040) and mutant NOTCH3 (0.18; p = 0.093). Relapse-free survival tended to be better for hypermutated tumors (0.53; p = 0.229). In conclusion, the overall spectrum of mutations in our Japanese stage III colorectal cancer cohort was similar to that in Western populations, but the frequencies of mutation for TP53, SOX9, and FBXW7 were higher, and the proportion of hypermutated tumors was lower. Multiple gene mutations appeared to impact relapse-free survival, suggesting that tumor genomic profiling can support precision medicine for colorectal cancer.

Effect modification by geographic area on the association between health literacy and self-rated health: a nationwide cross-sectional study in Japan.

BACKGROUND: Health literacy (HL) has gained increasing attention as a factor related to health behaviors and outcomes. This study aimed to investigate geographic differences in HL levels and effect modification by geographic area on their relationship with self-rated health in the Japanese population using a nationwide sample. METHODS: Data for this study were derived from a nationally representative cross-sectional survey on health information access for consumers in Japan using a mailed self-administered questionnaire in 2020 (INFORM Study 2020). Valid responses from 3,511 survey participants, selected using two-stage stratified random sampling, were analyzed in this study. HL was measured using the Communicative and Critical Health Literacy Scale (CCHL). Multiple regression and logistic regression analyses were conducted to examine the associations between geographic characteristics and HL and effect modification on the association between HL and self-rated health by geographic area, controlling for sociodemographic characteristics. RESULTS: The mean HL score was 3.45 (SD = 0.78), somewhat lower compared with previous studies on the Japanese general population. HL was higher in Kanto area than in Chubu area, after controlling for sociodemographic factors and municipality size. Furthermore, HL was positively associated with self-rated health after controlling for sociodemographic and geographic factors; however, this association was more evident in eastern areas than in western areas. CONCLUSION: The findings indicate geographic differences in HL levels and effect modification by geographic area on the relationship between HL and self-rated health in the general Japanese population. HL was more strongly associated with self-rated health in eastern areas than in western areas. Further investigation is needed to explore the moderating effects of areal features, including the distribution of primary care physicians and social capital, when formulating strategies to improve HL in different contexts.

Clinical trial design and analysis for comparing three treatments with intra-individual right- and left-hand data.

BACKGROUND: Chemotherapy-induced peripheral neuropathy can occur in the right and left hand. Studies on prevention treatments for chemotherapy-induced peripheral neuropathy have largely adopted either self-controlled designs or parallel designs to compare two preventive treatments. When three treatment options (two experimental treatments and a control treatment) are available, both designs can be extended. However, no clinical trials have adopted a self-controlled design to compare three prevention treatments for chemotherapy-induced peripheral neuropathy. The incomplete block crossover design for more than two treatments can be extended to compare three treatments in the self-controlled design. In simple extension, some of the participants receive two experimental treatments in both hands; however, it may be difficult to administer different experimental treatments in both hands for practical reasons, such as a concern for the different types of unexpected adverse events. This study proposes a design and analysis method appropriate for the situation where only one experimental treatment is provided to each participant. METHODS: We assume clinical trials to compare each of the two experimental treatments (E1 and E2) with the control treatment (C) and between two experimental treatments only when both experimental treatments are superior to the control treatment. We propose a self-controlled design, which equally randomizes to four arms to adjust for the dominant hand effect: Arm 1: E1 for right hand, C for left hand; Arm 2: C for right hand, E1 for left hand; Arm 3: E2 for right hand, C for left hand; and Arm 4: C for right hand, E2 for left hand. We compare operating characteristics of the proposed design with the three-arm parallel design in which the same treatment is performed in both hands by participants. We also assess three proposed analysis methods for comparisons between experimental treatments in the self-controlled design under several conditions of correlations between right and left hands using simulation studies. RESULTS: The simulation studies showed that the proposed design was more powerful than the three-arm parallel design when correlation was 0.3 or higher. For comparisons between experimental treatments, the methods based on the regression model, including the outcome of hands with C as a covariate, had the highest power under modest to high correlation among the analysis methods in the self-controlled design. CONCLUSION: The proposed design can improve the power for comparing between two experimental treatments and the control treatment. Our design is useful in situations where it is undesirable for participants to receive different experimental treatments in both hands for practical reasons.

Non-specific symptoms as a prodrome of immune-related adverse events in patients with non-small cell lung cancer receiving nivolumab: a consecutive analysis of 200 patients.

PURPOSE: Immune checkpoint blockade therapy is the standard treatment for metastatic or refractory non-small cell lung cancer (NSCLC). However, it is associated with immune-related adverse events (irAEs). irAEs are sometimes fatal; however, an efficient method for early irAEs detection has not been developed because their onset timing varies. We examined the significance of non-specific symptoms as a prodrome of irAEs in patients with NSCLC. METHODS: We reviewed consecutive patients who received nivolumab at a dosage of 3 mg/kg every 2 weeks for metastatic NSCLC between December 2015 and August 2017. Patient demographics, irAEs and signal symptoms were recorded. Non-specific symptoms (fever and fatigue) occurred 7 days or earlier before the onset of irAEs were considered signal symptoms. For statistical analyses, the association between irAEs and clinical information, including signal symptoms, was evaluated using Fisher's exact test and logistic regression. RESULTS: A total of 200 patients received nivolumab; 131 (65.5%) were male, their median age was 63 years (range 30-83), 174 (87.0%) had performance status of 0-1. Signal symptoms occurred in 38 (19.0%) of the 77 patients (38.5%) who experienced irAEs, and were positively associated with the occurrence of irAEs (P < 0.01). Multivariate analysis showed that the occurrence of irAEs was significantly higher in patients with PS 0-1 [odds ratio (OR) 7.01; 95% confidence intervals (CI), 1.69-29.13] and patients experienced signal symptoms (OR 17.30; 95% CI, 6.51-45.99). CONCLUSION: The occurrence of signal symptoms could be used in the early detection and management of irAEs in patients during immune checkpoint blockade therapy.

Family cancer history and smoking habit associated with sarcoma in a Japanese population study.

Sarcoma is a rare cancer, and little is known about the etiology, lifestyle epidemiology, and actual circumstances of treatment in hospitals in Japan. Understanding these issues is essential for the effective prevention and treatment of sarcoma. We therefore investigated the incidence of a personal and family cancer history in a total of 1320 sarcoma patients at the National Cancer Center Hospital. In addition, obesity, hypertension, dyslipidemia, diabetes mellitus, drinking, smoking, age and sex were compared in a descriptive study of 1159 of these sarcoma patients who were ≥ 20 years of age, and 7738 controls derived from the National Health and Nutrition Examination Survey in Japan. A total of 8% of sarcoma patients had a personal history of another cancer, and 30% of soft tissue sarcoma patients had a family cancer history in a first-degree relative (malignant peripheral nerve sheath tumor, 52%; leiomyosarcoma, 46%). A smoking habit was associated with the development of sarcoma (odds ratio [OR], 2.05; 95% confidence interval, 1.78-2.37; p < 0.01). According to the histology, the ORs for undifferentiated pleomorphic sarcoma (UPS) of bone, UPS of soft tissue, and liposarcoma were 5.71, 3.04, and 2.92, respectively. A family cancer history may be associated with certain soft tissue sarcomas, and a smoking habit was significantly associated with the development of sarcomas; however, further studies are necessary.

Robust automated prediction of the revised Vienna Classification in colonoscopy using deep learning: development and initial external validation.

BACKGROUND: Improved optical diagnostic technology is needed that can be used by also outside expert centers. Hence, we developed an artificial intelligence (AI) system that automatically and robustly predicts the pathological diagnosis based on the revised Vienna Classification using standard colonoscopy images. METHODS: We prepared deep learning algorithms and colonoscopy images containing pathologically proven lesions (56,872 images, 6775 lesions). Four classifications were adopted: revised Vienna Classification category 1, 3, and 4/5 and normal images. The best algorithm-ResNet152-in the independent internal validation (14,048 images, 1718 lesions) was used for external validation (255 images, 128 lesions) based on neoplastic and non-neoplastic classification. Diagnostic performance of endoscopists was compared using a computer-assisted interpreting test. RESULTS: In the internal validation, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for adenoma (category 3) of 84.6% (95% CI 83.5-85.6%), 99.7% (99.5-99.8%), 90.8% (89.9-91.7%), 89.2% (88.5-99.0%), and 89.8% (89.3-90.4%), respectively. In the external validation, ResNet152's sensitivity, specificity, PPV, NPV, and accuracy for neoplastic lesions were 88.3% (82.6-94.1%), 90.3% (83.0-97.7%), 94.6% (90.5-98.8%), 80.0% (70.6-89.4%), and 89.0% (84.5-93.6%), respectively. This diagnostic performance was superior to that of expert endoscopists. Area under the receiver-operating characteristic curve was 0.903 (0.860-0.946). CONCLUSIONS: The developed AI system can help non-expert endoscopists make differential diagnoses of colorectal neoplasia on par with expert endoscopists during colonoscopy. (229/250 words).

Multicenter phase II trial of trastuzumab deruxtecan for HER2-positive unresectable or recurrent biliary tract cancer: HERB trial.

Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate composed of a humanized monoclonal anti-HER2 antibody, a cleavable tetrapeptide-based linker and a potent topoisomerase I inhibitor. The drug's efficacy has been proven in HER2-positive breast and gastric cancers. The rate of HER2 positivity in biliary tract cancer (BTC) has been reported to be 5-20%, and case reports and clinical trials have suggested that HER2 inhibitors might be active in HER2-positive BTC. Here we describe the rationale and design of the phase II HERB trial that will evaluate the efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing unresectable or recurrent BTC. The primary end point will be the centrally assessed objective response rate in HER2-positive patients.

Trastuzumab deruxtecan (DS-8201) is a new drug against HER2, a receptor on cell membranes that has sensitivity to targeted inhibitors. The drug's efficacy has been proven in HER2-positive breast and gastric cancers. Some studies have suggested that HER2 inhibitors might be active in HER2-positive biliary tract cancers. This article describes the design of a new clinical trial. The HERB trial is designed to evaluate the efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing biliary tract cancers. Clinical trial registration: JMA-IIA00423.

Confidence interval for micro-averaged F 1 and macro-averaged F 1 scores.

A binary classification problem is common in medical field, and we often use sensitivity, specificity, accuracy, negative and positive predictive values as measures of performance of a binary predictor. In computer science, a classifier is usually evaluated with precision (positive predictive value) and recall (sensitivity). As a single summary measure of a classifier's performance, F 1 score, defined as the harmonic mean of precision and recall, is widely used in the context of information retrieval and information extraction evaluation since it possesses favorable characteristics, especially when the prevalence is low. Some statistical methods for inference have been developed for the F 1 score in binary classification problems; however, they have not been extended to the problem of multi-class classification. There are three types of F 1 scores, and statistical properties of these F 1 scores have hardly ever been discussed. We propose methods based on the large sample multivariate central limit theorem for estimating F 1 scores with confidence intervals.

Accuracy of exercise-based tests for estimating cardiorespiratory fitness and muscle strength in early-stage breast cancer survivors in Japan.

PURPOSE: We aimed to examine whether cardiorespiratory fitness and leg strength can be estimated based on their relationship with physical performance tests in Japanese breast cancer survivors. METHODS: Participants were 50 sedentary women aged 20 to 59 years who have received breast surgery in the past 2 to 13 months after diagnosis of invasive breast cancer (stage I-IIa). Cardiorespiratory fitness and leg strength were measured by peak oxygen consumption (VO2peak), and one-repetition maximum for leg press (leg press 1RM). Physical performance tests were performed 6-min walk test, chair stand test, and grip strength. Using multiple regression analysis, we developed prediction equations for VO2peak and leg strength based on their associations with the physical performance tests. The validity of the estimation equations was assessed using Bland-Altman plots. RESULTS: Mean age, VO2peak, and leg press 1RM were 48 ± 6 years, 25.0 ± 3.6 mL/kg/min, and 95 ± 32 kg, respectively. Multiple regression analysis yielded 6-min walk test distance, age, height, and body weight as predictors of VO2peak. Measured VO2peak and predicted VO2peak showed a moderate positive correlation (r = 0.463, p < 0.001). Chair stand test, grip strength, age, height, and body weight were selected as predictors of leg press 1RM. There was a strong positive correlation between predicted and measured leg press 1RM (r = 0.754, p < 0.001). CONCLUSION: The results suggest that leg strength can be predicted using physical performance tests. However, further examination may be needed to determine whether cardiorespiratory fitness can be predicted based on 6-min walk test.

Cardiorespiratory fitness in breast cancer survivors: a randomised controlled trial of home-based smartphone supported high intensity interval training.

BACKGROUND: A strategy for maintaining and/or improving cardiorespiratory fitness (CRF) in the growing population of cancer survivors is of major clinical importance, especially in the COVID-19 era. The effect of unsupervised high-intensity interval training (HIIT) on increasing CRF in breast cancer survivors is unknown. PURPOSE: The purpose of this study was to determine whether the newly developed habit-B programme, which involves home-based smartphone-supported HIIT using body weight exercises, improves CRF in early-stage breast cancer survivors. METHODS: This single-centre, 12-week, parallel-group, single-blind, randomised controlled trial involved 50 women with stage I-IIa breast cancer, aged 20-59 years, who had completed initial treatment except for hormone therapy. Participants were randomised to either the exercise or control group. The primary outcome was the 12-week change in peak oxygen uptake [Formula: see text]. Other outcomes included muscle strength, 6 min walk test, resting heart rate, physical activity, fatigue, safety and quality of life. RESULTS: The change in [Formula: see text] and leg strength increased significantly in the exercise group compared with the control group (p<0.01). Changes in other outcomes were not significantly different between the groups. CONCLUSION: A home-based HIIT intervention can lead to improve CRF and muscle strength in early-stage breast cancer survivors.