Individualization in the first-line treatment of advanced ovarian cancer based on the mechanism of action of molecularly targeted drugs

International Journal of Clinical Oncology - With the development of poly(ADP-ribose) polymerase inhibitors, the treatment of advanced ovarian cancer is changing dramatically. The purpose of this...     

Human papillomavirus genotype contribution to cervical cancer and precancer: Implications for screening and vaccination in Japan

To obtain baseline data for cervical cancer prevention in Japan, we analyzed human papillomavirus (HPV) data from 5045 Japanese women aged less than 40 years and diagnosed with cervical abnormalities at 21 hospitals during 2012‐2017. These included cervical intraepithelial neoplasia grade 1 (CIN1, n = 573), CIN2‐3 (n = 3219), adenocarcinoma in situ (AIS, n = 123), and invasive cervical cancer (ICC, n = 1130). The Roche Linear Array was used for HPV genotyping. The HPV type‐specific relative contributions (RCs) were estimated by adding multiple infections to single types in accordance with proportional weighting attributions. Based on the comparison of type‐specific RCs between CIN1 and CIN2‐3/AIS/ICC (CIN2+), RC ratios were calculated to estimate type‐specific risks for progression to CIN2+. Human papillomavirus DNA was detected in 85.5% of CIN1, 95.7% of CIN2‐3/AIS, and 91.2% of ICC. Multiple infections decreased with disease severity: 42.9% in CIN1, 40.4% in CIN2‐3/AIS, and 23.7% in ICC (P < .0001). The relative risk for progression to CIN2+ was highest for HPV16 (RC ratio 3.78, 95% confidence interval [CI] 3.01‐4.98), followed by HPV31 (2.51, 1.54‐5.24), HPV18 (2.43, 1.59‐4.32), HPV35 (1.56, 0.43‐8.36), HPV33 (1.01, 0.49‐3.31), HPV52 (0.99, 0.76‐1.33), and HPV58 (0.97, 0.75‐1.32). The relative risk of disease progression was 1.87 (95% CI, 1.71‐2.05) for HPV16/18/31/33/35/45/52/58, but only 0.17 (95% CI, 0.14‐0.22) for HPV39/51/56/59/66/68. Human papillomavirus 16/18/31/33/45/52/58/6/11 included in a 9‐valent vaccine contributed to 89.7% (95% CI, 88.7‐90.7) of CIN2‐3/AIS and 93.8% (95% CI, 92.4‐95.3) of ICC. In conclusion, our data support the Japanese guidelines that recommend discriminating HPV16/18/31/33/35/45/52/58 genotypes for CIN management. The 9‐valent vaccine is estimated to provide over 90% protection against ICC in young Japanese women.     

How I do it: Endoscopic diagnosis for superficial non-ampullary duodenal epithelial tumors

There are no reports on detailed endoscopic diagnosis of superficial non-ampullary duodenal epithelial tumors (SNADET) except for relatively small case series. Herein, we conducted a prospective observational study to investigate the relationship between endoscopic findings and histopathological diagnosis of SNADET. A total of 163 SNADET diagnosed using magnified endoscopic examination with image-enhanced endoscopy (IEE-ME) were prospectively registered in this study. We investigated location, size, macroscopic type, color, and IEE-ME findings including surface structure (closed- or open-loop) and presence of white opaque substance (WOS) in SNADET. We analyzed association between these findings and histopathological diagnosis of SNADET based on the Vienna classification (VCL) using logistic regression analysis. In univariate analysis, lesion size, superficial structure, and WOS deposition showed statistical significance, and the oral side of the lesion location showed statistical tendency for association with VCL C4/5. In multivariate analysis, lesion size (odds ratio [OR], 2.92; 95% CI, 1.94–4.39; P < 0.05) and negative WOS (OR, 5.59; 95% CI, 1.72–18.1; P < 0.05) were significantly associated with VCL C4/5 lesions. Superficial structures with a closed-loop pattern on the surface showed statistical tendency for predicting VCL C4/5 lesions (OR, 2.15; 95% CI, 0.86–5.37; P = 0.10). Based on these findings, we concluded that negative WOS by IEE-ME and lesion size were independent predictors of VCL C4/5 SNADET. These factors may help us to understand of pathophysiology of SNADET and to select appropriate therapeutic strategies.     

The Association Between Habitual Sleep Duration and Mortality According to Sex and Age: The Japan Public Health Center-based Prospective Study

BackgroundShort and long sleep durations are associated with mortality outcomes. The association between sleep duration and mortality outcomes may differ according to sex and age.MethodsParticipants of the Japan Public Health Center-based prospective study (JPHC Study) were aged 40–69 years and had completed a detailed questionnaire on lifestyle factors. Sex- and age-stratified analyses on the association between habitual sleep duration and mortality from all-causes, cardiovascular diseases (CVD), cancer and other causes included 46,152 men and 53,708 women without a history of CVD or cancer. Cox proportional hazards regression models, adjusted for potential confounders, were used to determine hazard ratios and 95% confidence intervals.ResultsMean follow-up time was 19.9 years for men and 21.0 years for women. In the multivariable sex-stratified models, some categories of sleep durations ≥8 hours were positively associated with mortality from all-causes, CVD, and other causes in men and women compared with 7 hours. The sex- and age-stratified analyses did not reveal any major differences in the association between sleep duration and mortality outcomes in groups younger and older than 50 years of age. The only exception was the significant interaction between sleep duration and age in women for mortality from other causes.ConclusionsSleep durations ≥8 hours are associated with mortality outcomes in men and women. Age may be an effect modifier for the association between sleep duration and mortality from other causes in women.Key words: all-cause mortality, CVD mortality, cancer mortality, general population, Japan, sleep duration     

Family history of cancer and subsequent risk of cancer: A large-scale population-based prospective study in Japan

Family history (FH) of cancer is an important factor of increased risk of several cancers. Although the association between FH of cancer and concordant cancer risk has been reported in many previous epidemiological studies, no comprehensive prospective study with adjustment for lifestyle habits has evaluated the association of FH of cancer and concordant cancer risk. We investigated the association between FH of cancer and concordant cancer risk in a Japanese population-based prospective study, initiated in 1990 for cohort I and in 1993 for cohort II. We analyzed data on 103,707 eligible subjects without a history of cancer who responded to a self-administered questionnaire including FH of cancer at baseline. Study subjects were followed through 2012 and analyzed using multivariable-adjusted Cox proportional hazards regression models. During 1,802,581 person-years of follow-up, a total of 16,336 newly diagnosed cancers were identified. Any site (Hazard ratios = 1.11 (95% confidence interval = 1.07–1.15]), esophagus (2.11 [1.00–4.45]), stomach (1.36 [1.19–1.55]), liver (1.69 [1.10–2.61]), pancreas (2.63 [1.45–4.79]), lung (1.51 [1.14–2.00]), uterus (1.93 [1.06–3.51]) and bladder cancers (6.06 [2.49–14.74]) with FH of the concordant cancer were associated with an increased risk compared to those without FH. Our findings suggest that having FH of cancer is associated with an increased risk of several concordant cancer incidences in an Asian population. Enquiring about FH of several types of cancer may be important in identifying groups at high-risk of those cancers.     

Development of a Cardiovascular Disease Risk Prediction Model Using the Suita Study,a Population-Based Prospective Cohort Study in Japan

Aim: To construct a risk prediction model for cardiovascular disease (CVD) based on the Suita study, an urban Japanese cohort study, and compare its accuracy against the Framingham CVD risk score (FRS) model.Methods: After excluding participants with missing data or those who lost to follow-up, this study consisted of 3,080 men and 3,470 women participants aged 30–79 years without CVD at baseline in 1989–1999. The main outcome of this study was incidence of CVD, defined as the incidence of stroke or coronary heart disease. Multivariable Cox proportional hazards models with stepwise selection were used to develop the prediction model. To assess model performance, concordance statistics (C-statistics) and their 95% confidence intervals (CIs) were calculated using a bootstrap procedure. A calibration test was also conducted.Results: During a median follow-up period of 16.9 years, 351 men and 241 women developed CVD. We formulated risk models with and without electrocardiogram (ECG) data that included age, sex, systolic blood pressure, diastolic blood pressure, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, lowdensity lipoprotein cholesterol, diabetes mellitus, smoking, and urinary protein as risk factors. The C-statistics of the Suita CVD risk models with ECG data (0.782; 95% CI, 0.766–0.799) and without ECG data (0.781; 95% CI, 0.765–0.797) were significantly higher than that of the FRS model (0.768; 95% CI, 0.750–0.785).Conclusions: The Suita CVD risk model is feasible to use and improves predictability of the incidence of CVD relative to the FRS model in Japan.