Association of Menopausal Hormone Therapy with Risk of Pancreatic Cancer: A Systematic Review and Meta-analysis of Cohort Studies.

BACKGROUND: Although menopausal hormone therapy (MHT) is commonly prescribed, little is known about the association between MHT use and risk of pancreatic cancer. METHODS: We searched PubMed, Embase, and Cochrane Library, from inception until April 20, 2022. The risk of bias was assessed with the Newcastle-Ottawa Quality Assessment Scale. Pooled relative risks (RR) for pancreatic cancer risk were calculated using random-effects models. We computed prediction intervals (PI) and performed subgroup meta-analyses. Meta-regression was performed to investigate the sources of heterogeneity. RESULTS: This study included 2,712,313 women from 11 cohort studies. There was no association between MHT and pancreatic cancer risk (RR, 0.92; 95% confidence interval (CI), 0.83-1.02; I2, 64%; 95% PI, 0.68-1.25). Subgroup meta-analyses of four studies stratified by MHT formulations showed inverse associations with the risk of pancreatic cancer (women receiving estrogen-only MHT: RR, 0.77; 95% CI, 0.64-0.94; I2, 57%; estrogen plus progestin MHT: RR, 0.85; 95% CI, 0.75-0.96; I2, 0%). Subgroup analysis defined by recency and duration of treatment did not reveal evidence of associations between MHT and pancreatic cancer risk. CONCLUSIONS: This study found no association between the overall use of MHT and risk of pancreatic cancer. However, among four studies with data on MHT formulations, subgroup analysis showed a decreased risk of pancreatic cancer among users of estrogen-only and combined estrogen-progestin therapy. Owing to the inconsistent findings between our main and subgroup analyses, future studies stratified by MHT formulations are warranted. IMPACT: The findings of this study indicate that future investigation should focus on MHT formulations.

Comparison of Severity of Genitourinary Syndrome of Menopause Symptoms After Carbon Dioxide Laser vs Vaginal Estrogen Therapy: A Systematic Review and Meta-analysis.

Importance: Vaginal estrogen for genitourinary syndrome of menopause (GSM) should be used with caution in women with contraindications, highlighting the need for effective treatment alternatives. Objective: To compare the severity of GSM after vaginal laser vs estrogen therapy. Data Sources: The PubMed, Embase, and Cochrane Library databases were searched for articles published from database inception to April 8, 2022, with no language restrictions. Reference lists were also searched. Study Selection: Randomized clinical trials (RCTs) that compared the use of lasers with vaginal estrogen in adults were selected. Data Extraction and Synthesis: Two investigators independently extracted data from included studies. The Cochrane risk of bias tool for RCTs was used to assess risk of bias of each study. A random-effects model was used to pool mean differences (MDs) with 95% CIs. Main Outcomes and Measures: Primary outcomes were Vaginal Analog Scale (VAS; higher scores indicate severer symptoms), Vaginal Health Index (VHI; higher scores indicate better vaginal health), Vaginal Maturation Index (VMI; higher scores indicate higher estrogen effect on the vaginal epithelium), Female Sexual Function Index (FSFI; higher scores indicate better female sexual function), and Sexual Quotient-Female (SQ-F; higher scores indicate better female sexual function) questionnaire scores. Urinary symptoms were assessed as an additional outcome. Data analyses were performed from April 9 to 12, 2022. Results: A total of 6 RCTs with 270 women with GSM were included (135 were randomized to laser therapy and 135 to estrogen therapy; mean age ranged from 54.6 to 61.0 years). No significant differences were found between carbon dioxide laser and vaginal estrogen from baseline to the end of follow-up in overall VAS scores (MD, -0.16; 95% CI, -0.67 to 0.36; I2, 33.31%), VHI (MD, 0.20; 95% CI, -0.56 to 0.97; I2, 83.25%), VMI (MD, -0.56; 95% CI, -1.14 to 0.02; I2, 35.07%), FSFI (MD, -0.04; 95% CI, -0.45 to 0.36; I2, 41.60%), and SQ-F (P = .37 based on 1 study). Other questionnaire-based outcome measures demonstrated no difference between groups from baseline to the end of follow-up for changes in urinary symptoms. Conclusions and Relevance: This systematic review and meta-analysis of RCTs found that vaginal laser treatment is associated with similar improvement in genitourinary symptoms as vaginal estrogen therapy. Further research is needed to test whether vaginal laser therapy could be a potential treatment option for women with contraindications to vaginal estrogen.

Association of hormone replacement therapy with risk of gastric cancer: a systematic review and meta-analysis.

Hormone replacement therapy (HRT) is widely used to relieve menopausal symptoms; however, it remains unclear whether the use of HRT was associated with gastric cancer. We conducted a systematic review and meta-analysis to synthesize available evidence. This study followed the PRISMA guideline to report meta-analysis. PubMed, Embase, and Cochrane library were searched from conception through 23 February 2022. Eligible studies reporting risk of gastric cancer after HRT were screened and accessed by two independent reviewers. Random-effects meta-analysis was used to calculate pooled risk estimate as relative risk (RR, 95% CI). Pre-established review protocol was registered in PROSPERO (CRD42021281260). Among the 1095 articles identified, we included 11 studies with 1,919,089 women in this meta-analysis. The combined risk estimate (RR, 0.72; 95% CI 0.64-0.81; I2 = 2%) indicated that the use of HRT was associated with a 28% reduction in risk of gastric cancer compared with those who had no HRT exposure. The narrow prediction interval (0.62-0.84) for gastric cancer risk suggested a low between-study variance. In subgroup analysis defined by HRT formulation, there were reduction in risks of gastric cancer after the use of estrogen-only therapy (Pooled RR, 0.63; 95% CI 0.51-0.77, I2 = 0%) and estrogen-progestin therapy (Pooled RR, 0.70; 95% CI 0.57-0.87; I2 = 0%), as compared with non-users. In this systematic review and meta-analysis, the use of HRT was associated with a reduced gastric cancer risk regardless of HRT formulation. Further investigations are warranted to confirm underlying mechanisms.

Association of Marital Status With Total and Cause-Specific Mortality in Asia.

Importance: Marital status has been shown to be associated with mortality, but evidence in Asian populations is limited. Objective: To examine the association of marital status with total and cause-specific mortality. Design, Setting, and Participants: This cohort study included individual participant data from 16 prospective studies in the Asia Cohort Consortium conducted between 1963 and 2015. Asian participants with complete information on marital and vital status were included. Study-specific hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards model and then pooled using a random-effects meta-analysis. The analysis began in February 2021 and ended in August 2021. Exposures: Marital status. Main Outcomes and Measures: All-cause and cause-specific mortality. Results: Of 623 140 participants (326 397 women [52.4%] and 296 743 men [47.6%]; mean [SD] age, 53.7 [10.2] years; mean [SD] follow-up time, 15.5 [6.1] years), 123 264 deaths were ascertained. Compared with married individuals, those who were unmarried had pooled HRs of 1.15 (95% CI, 1.07-1.24) for total mortality, 1.12 (95% CI, 1.03-1.22) for cerebrovascular disease mortality, 1.20 (95% CI, 1.09-1.31) for coronary heart disease mortality, 1.17 (95% CI, 1.07-1.28) for circulatory system diseases mortality, 1.06 (95% CI, 1.01-1.11) for cancer mortality, 1.14 (95% CI, 1.05-1.23) for respiratory diseases mortality, and 1.19 (95% CI, 1.05-1.34) for external causes of death. Positive associations with total mortality were also observed for those who were single (HR, 1.62; 95% CI, 1.41-1.86), separated (HR, 1.35; 95% CI, 1.13-1.61), divorced (HR, 1.38; 95% CI, 1.13-1.69), and widowed (HR, 1.09; 95% CI, 1.04-1.13). In subgroup analyses, the positive association persisted across baseline health conditions, and the risk of death was more pronounced among men or people younger than 65 years. Conclusions and Relevance: This large pooled cohort study of individual participant data provides strong evidence that being unmarried, as well as belonging to the unmarried subcategories, was positively associated with total and cause-specific mortality. Investment of targeted social support services might need to be considered in light of the mortality differences between married and unmarried individuals.

Dietary glycemic index, glycemic load and mortality: Japan Public Health Center-based prospective study.

PURPOSE: Long-term associations of dietary glycemic index (GI) and glycemic load (GL) with mortality outcomes remain unclear. METHODS: The present analysis included 72,783 participants of the Japan Public Health Center-based Prospective Study. Participants who responded to the 5-year follow-up questionnaire in 1995-1999 were followed-up until December 2015. We estimated the risk of total and cause-specific mortality associated with GI and GL using Cox proportional hazards regression models. RESULTS: During 1,244,553 person years of follow-up, 7535 men and 4913 women died. GI was positively associated with all-cause mortality. As compared with the lowest quartile, the multivariable HR for those who had the highest quartile of GI was 1.14 (95% CI 1.08-1.20). The HRs for death comparing the highest with the lowest quartile were 1.28 (95% CI 1.14-1.42) for circulatory system diseases, 1.33 (95% CI 1.14-1.55) for heart disease, 1.32 (95% CI 1.11-1.57) for cerebrovascular disease, and 1.45 (95% CI 1.18-1.78) for respiratory diseases. GI was not associated with mortality risks of cancer and digestive diseases. GL showed a null association with all-cause mortality (highest vs lowest quartile; HR 1.04; 95% CI 0.96-1.12). However, among those who had the highest quartile of GL, the HRs for death from circulatory system diseases was 1.24 (95% CI 1.05-1.46), cerebrovascular disease was 1.34 (95% CI 1.03-1.74), and respiratory diseases was 1.35 (95% CI 1.00-1.82), as compared with the lowest quartile. CONCLUSION: In this large prospective cohort study, dietary GI and GL were associated with mortality risks.

Effect and cost-effectiveness of national gastric cancer screening in Japan: a microsimulation modeling study.

BACKGROUND: A national endoscopic screening program for gastric cancer was rolled out in Japan in 2015. We used a microsimulation model to estimate the cost-effectiveness of current screening guidelines and alternative screening strategies in Japan. METHODS: We developed a microsimulation model that simulated a virtual population corresponding to the Japanese population in risk factor profile and life expectancy. We evaluated 15 endoscopic screening scenarios with various starting ages, stopping ages, and screening intervals. The primary outcomes were quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratio. Cost-effective screening strategies were determined using a willingness-to-pay threshold of $50,000 per QALY gained. One-way sensitivity and probabilistic sensitivity analyses were done to explore model uncertainty. RESULTS: Using the threshold of $50,000 per QALY, a triennial screening program for individuals aged 50 to 75 years was the cost-effective strategy, with an incremental cost-effectiveness ratio of $45,665. Compared with no endoscopic screening, this strategy is predicted to prevent 63% of gastric cancer mortality and confer 27.2 QALYs gained per 1000 individuals over a lifetime period. Current screening guidelines were not on the cost-effectiveness efficient frontier. The results were robust on one-way sensitivity analyses and probabilistic sensitivity analysis. CONCLUSIONS: This modeling study suggests that the endoscopic screening program in Japan would be cost-effective when implemented between age 50 and 75 years, with the screening repeated every 3 years. These findings underscore the need for further evaluation of the current gastric cancer screening recommendations.

Cancer incidence attributable to tuberculosis in 2015: global, regional, and national estimates.

BACKGROUND: Tuberculosis is associated with increased risk of cancer. However, the impact of tuberculosis on global cancer burden is unknown. METHODS: We performed random-effects meta-analyses and meta-regressions of studies reporting the association between tuberculosis and cancer risks by searching PubMed, Web of Science, Embase, Cochrane library, and CINAHL from inception to 1 June 2019. Population attributable fractions (PAFs) of cancer incidence attributable to tuberculosis were calculated using relative risks from our meta-analyses and tuberculosis prevalence data from Global Health Data Exchange by age, sex, and country. The study has been registered with PROSPERO (CRD42016050691). RESULTS: Fourty nine studies with 52,480 cancer cases met pre-specified inclusion criteria. Tuberculosis was associated with head and neck cancer (RR 2.64[95% CI 2.00-3.48]), hepatobiliary cancer (2.43[1.82-3.25]), Hodgkin's lymphoma (2.19[1.62-2.97]), lung cancer (1.69[1.46-1.95]), gastrointestinal cancer (1.62[1.26-2.08]), non-Hodgkin's lymphoma (1.61[1.34-1.94]), pancreatic cancer (1.58[1.28-1.96]), leukaemia (1.55[1.25-1.93]), kidney and bladder cancer (1.54[1.21-1.97]), and ovarian cancer (1.43[1.04-1.97]). We estimated that 2.33%(1.14-3.81) or 381,035(187145-623,404) of global cancer incidences in 2015 were attributable to tuberculosis. The PAFs varied by Socio-demographic Index (SDI)-ranging from 1.28% (0.57-2.31%) in the high-SDI countries to 3.51% (1.84-5.42%) in the middle-SDI countries. Individually, China and India accounted for 47% of all tuberculosis-related cancer cases. CONCLUSIONS: Tuberculosis is associated with increased risk of cancer at ten sites. The burden of tuberculosis attributable cancer skewed towards lower resource countries. Research priorities are to better understand regional disparities and underlying mechanism linking tuberculosis and cancer development.

Association of hormone replacement therapy with mortality in colorectal cancer survivor: a systematic review and meta-analysis.

BACKGROUND: Hormone replacement therapy (HRT) use has shown to be associated with a reduced risk of colorectal cancer, however, its impact on survival among women with colorectal cancer remains uncertain. This meta-analysis aimed to systematically assess the survival benefit of HRT use in patients with colorectal cancer. METHODS: PRISMA guidelines for the reporting of meta-analyses were followed. We systematically searched PubMed, Embase, Cochrane library, Scopus, and PsycINFO from inception to 12 January 2019, with no language restrictions, for randomized controlled trials and cohort studies reporting the association between hormone replacement therapy and risk of colorectal cancer mortality or all-cause mortality in colorectal cancer survivors. We used the Newcastle-Ottawa Scale to assess the risk of bias of the included studies. We summarized the association as hazard ratio (HR; 95% CI) using random-effects meta-analysis. The study protocol was registered in PROSPERO (CRD42017071914). RESULTS: Of 1648 articles identified, five cohorts including 10,013 colorectal cancer survivors were included in this meta-analysis. Compared with women with no prior use of HRT, those reporting current use of HRT had lower risks of colorectal cancer-specific mortality (HR, 0.71 [95% CI, 0.62-0.80], I2 = 0%) and overall mortality (HR, 0.74 [95% CI, 0.67-0.81], I2 = 0%). Low between-study variance was also suggested by the narrow prediction interval for colorectal cancer-specific mortality (0.58-0.86) and overall mortality (0.63-0.87), which indicated that a future study will show survival benefits in women with current HRT use compared with those with no HRT exposure. Inverse associations with colorectal cancer-specific (HR, 1.02 [95% CI, 0.82-1.28], I2 = 0%) and overall mortality (HR, 1.07 [95% CI, 0.90-1.27], I2 = 0%) were not observed for former users of HRT. Sensitivity analyses revealed no differences in the risk estimates between two groups. CONCLUSIONS: The findings suggest that the current use of HRT is associated with lower risks of colorectal cancer-specific and overall mortality in patients with colorectal cancer. Further investigations to elucidate the underlying mechanism are warranted.

Mass-like Dieulafoy's lesion associated with advanced gastric cancer at the antrum of stomach: a case report and literature review.

BACKGROUND: Dieulafoy's lesion, also known as a caliber-persistent artery, is a shallow, small, and rare lesion that occurs along the lesser curvature of proximal stomach. It is rare for a Dieulafoy's lesion to present as a mass-like lesion that coexists with gastric cancer. To our best knowledge, we report the first case and histopathological pictures of a mass-like Dieulafoy's lesion coexisting with advanced gastric cancer in the antrum of the stomach. CASE PRESENTATION: A 57-year-old female presented with a 6-month history of intermittent epigastric dull pain and dyspepsia. Subsequent upper gastrointestinal endoscopy revealed a friable mass that was located between the distal antrum and the pyloric ring. Biopsy revealed it to be an intestinal type adenocarcinoma. Subtotal gastrectomy was performed after neoadjuvant chemotherapy. Grossly, a large irregular plaque-like tumor lesion was noted at the anterior wall of the distal antrum and pylorus ring near the lesser curvature, measuring 5.6 × 4.8 × 1.0 cm. Histopathological examination of the resected stomach revealed that the plaque-like lesion largely consisted of numerous abnormally large-caliber and tortuous arteries in the submucosa. The increased fibrosis of the submucosa resulted in the formation of elevated plaque. The intestinal type adenocarcinoma was noted to be largely confined to the mucosa layer, with focal submucosal and muscular propria involvement. The patient was discharged one week after the subtotal gastrectomy, and she was alive and well 17 months after discharge, with no major complications. CONCLUSION: This is the first case of a mass-like Dieulafoy's lesion coexisting with advanced gastric cancer at the distal antrum area. This case highlights the possibility of life-threatening gastric bleeding after mucosal resection or biopsy that could be encountered by endoscopists.