Height, body mass index, physical activity, and risk of colorectal cancer in relation to expression of insulin receptor: The Japan Public Health Center-based Prospective Study.

To ascertain the involvement of insulin receptors (IRs) in colorectal carcinogenesis, we investigated the association of height, body mass index (BMI), and physical activity with colorectal cancer (CRC) and two subtypes of CRC according to the expression level of IR. We utilized data from a large-scale, population-based prospective cohort study of 18,158 middle-aged and elderly subjects in Akita and Okinawa, Japan. In the statistical analysis, we used the Cox proportional hazards model and estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of CRC and its subtypes as defined by immunohistochemistry of IRß, a transmembrane subunit of IR. In the IRß-defined subtypes, height showed no apparent association with the risk of IRß-positive CRC. In contrast, a multivariable HR of IRß-positive CRC was 1.77 (95% CI = 1.04-3.03) with a BMI of ≥30.0 kg/m2 (i.e., obesity), compared to a BMI of <25.0 kg/m2. Further, an increase in physical activity was significantly associated with decreased risk of IRß-positive CRC (multivariable HR per 5 METs-hour/day = 0.93, 95% CI = 0.88-0.99). Meanwhile, we found no significant association between any exposure and IRß-negative CRC. Likewise, heterogeneity between the two subtypes of CRC was not statistically significant. These findings imply that obesity and physical activity exert promoting and suppressing effects on the development of CRC expressing IRs, respectively.

Awareness, information sources, and beliefs regarding palliative care in the general population in Japan: a nationwide cross-sectional survey (INFORM study 2023).

BACKGROUND: The diversification of information sources and changes in social structures necessitates updates on the state of public awareness of palliative care. Therefore, we clarified the status and determinants of awareness, information sources, and beliefs, regarding palliative care in Japan. METHODS: This nationwide cross-sectional survey included 10 000 participants aged ≥20 years enrolled through random sampling using a two-stage stratification in 2023. We used a mailed self-administered questionnaire (INFORM Study 2023). The questionnaire items were selected (partially modified) from the Health Information National Trends Survey (USA) to ensure comparability, included palliative care awareness, information sources, and beliefs. Weighted logistic regression was conducted to explore the determinants of awareness. RESULTS: Of the 3452 participants that responded (response rate: 35.3%), 65.2% had palliative care awareness. The weighted logistic regression analysis revealed that respondents less likely to have any palliative care awareness were younger, were male, had limited education history, had lower household income, and were non-Internet users. Of these, sex had the clear association (adjusted odds ratio for female vs. male: 3.20 [95% CI: 2.66-3.85]). Across all age groups, healthcare professionals (58.5%) and the Internet (30.5%) were the most trusted source of information. Younger participants frequently received information online. Most participants believed that palliative care was beneficial, although 82.0% associated it with death. CONCLUSIONS: The Japanese population had a relatively high palliative care awareness, with the majority trusting information from healthcare professionals rather than the Internet. Further efforts are warranted to address barriers to receiving trustworthy palliative care information.

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.

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.

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.

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.

Dietary vitamin D intake and risk of colorectal cancer according to vitamin D receptor expression in tumors and their surrounding stroma.

BACKGROUND: Colorectal Cancer (CRC) has been molecularly classified into several subtypes according to tumor, stromal, and immune components. Here, we investigated whether the preventive effect of vitamin D on CRC varies with subtypes defined by Vitamin D receptor (VDR) expression in tumors and their surrounding stroma, along with the association of somatic mutations in CRC. METHODS: In a population-based prospective study of 22,743 Japanese participants, VDR expression levels in tumors and their surrounding stroma were defined in 507 cases of newly diagnosed CRC using immunohistochemistry. Hazard ratios of CRC and its subtypes according to dietary vitamin D intake were estimated using multivariable Cox proportional hazards models. RESULTS: Dietary vitamin D intake was not associated with CRC or its subtypes defined by VDR expression in tumors. However, an inverse association was observed for CRC with high VDR expression in the stroma (the highest tertile vs the lowest tertile: 0.46 [0.23-0.94], Ptrend = 0.03), but not for CRC with low VDR expression in the stroma (Pheterogeneity = 0.02). Furthermore, CRC with high VDR expression in the stroma had more somatic TP53 and BRAF mutations and fewer APC mutations than those with low VDR expression in the stroma. CONCLUSIONS: This study provides the first evidence that the preventive effect of vitamin D on CRC depends on VDR expression in the stroma rather than in the tumors. CRC with high VDR expression in the stroma is likely to develop through a part of the serrated polyp pathway, which tends to occur with BRAF but not with APC mutations.

Trastuzumab Deruxtecan in Human Epidermal Growth Factor Receptor 2-Expressing Biliary Tract Cancer (HERB; NCCH1805): A Multicenter, Single-Arm, Phase II Trial.

PURPOSE: Treatment options for patients with unresectable or recurrent biliary tract cancer (BTC) who progress on a gemcitabine-containing regimen are limited. In addition, the significance of anti-human epidermal growth factor receptor 2 (HER2) therapy in HER2-expressing BTC has not been sufficiently investigated. METHODS: In this phase II trial, participants from five institutions in Japan were enrolled. Eligible patients had pathologically confirmed unresectable or recurrent BTC with centrally confirmed HER2-positive (immunohistochemistry [IHC]3+ or IHC2+ and in situ hybridization [ISH]+) or HER2-low (IHC2+ and ISH-, IHC1+, and IHC0 and ISH+) and were refractory or intolerant to a gemcitabine-containing regimen. The patients received 5.4 mg/kg trastuzumab deruxtecan (T-DXd) once every 3 weeks until disease progression or unacceptable toxicity. The primary end point was the confirmed objective response rate (ORR) in HER2-positive BTC by an independent central review (threshold ORR, 15%; expected ORR, 40%). RESULTS: A total of 32 patients were enrolled and treated. Among these patients, 22 with HER2-positive disease comprised the primary efficacy population and had a confirmed ORR of 36.4% (90% CI, 19.6 to 56.1; P = .01), meeting the primary end point. Eight with HER2-low disease comprised the exploratory population and had a confirmed ORR of 12.5%. The most common ≥grade 3 treatment-related adverse events were anemia (53.1%) and neutropenia (31.3%). Eight patients (25.0%) had interstitial lung disease (ILD), including two grade 5 events. CONCLUSION: T-DXd showed promising activity in patients with HER2-positive BTC and a signal of efficacy in patients with HER2-low BTC. Although the safety profile was generally manageable, ILD requires careful monitoring and early intervention.

A phase 3 study (PATHWAY) of palbociclib plus tamoxifen in patients with HR-positive/HER2-negative advanced breast cancer.

Palbociclib combined with endocrine therapy is approved for treating patients with hormone-receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer; however, data on palbociclib combined with tamoxifen are limited. We investigated the efficacy and safety of palbociclib-tamoxifen in patients with HR+/HER2- advanced breast cancer. This double-blind phase 3 study included 184 women who were randomly assigned 1:1 to receive palbociclib-tamoxifen or placebo-tamoxifen. Pre/perimenopausal women also received goserelin. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. Median PFS was 24.4 months (95% confidence interval [CI], 13.1-32.4) with palbociclib-tamoxifen and 11.1 months (95% CI, 7.4-14.6) with placebo-tamoxifen (hazard ratio [HR], 0.60; 95% CI, 0.43-0.85; P = 0.002). Palbociclib-tamoxifen improved PFS in patients who were treated with first-line or second-line endocrine therapy and pre-, peri-, and postmenopausal patients. Though OS data are still immature (median not reached in both groups), an overall risk reduction of 27% (HR, 0.73; 95% CI, 0.44-1.21) with palbociclib-tamoxifen was observed at the time of PFS analysis. The most common grade 3/4 adverse event with palbociclib-tamoxifen was neutropenia (89.0% [none were febrile] versus 1.1% with placebo-tamoxifen). There were no deaths owing to adverse events in either group. Among patients with HR+/HER2- advanced breast cancer, palbociclib-tamoxifen resulted in significantly longer PFS than tamoxifen alone. Early OS data showed a trend favoring palbociclib-tamoxifen. Trial registration: ClinicalTrials.gov number, NCT03423199. Study registration date: February 06, 2018.