Comparing treatments for basal cell carcinoma in terms of long‐term treatment‐failure: a network meta‐analysis

Although many variations of guidelines have been released, there is limited research that compares multiple treatment strategies for basal cell carcinoma (BCC). The aim of this study was to systematically review the studies reporting on multiple treatments for BCC with systematic review and network meta‐analyses. Search formulas for databases, such as PubMed, EMBASE, Web of Science Core Collection and Cochrane Central Register of Controlled Trials, were created with the support of Cochrane Japan. The patient‐level and tumour‐level meta‐analyses were performed for both the long‐term treatment‐failure and treatment‐success. Of the 1464 studies identified from the database and hand searches, 14 met our inclusion criteria. These 14 studies included 2524 patients and 1738 tumours. Our study indicated that the incidence of treatment‐failure of invasive treatments such as surgery and Mohs micrographic surgery was significantly lower than that of superficial therapies such as cryotherapy, photodynamic therapy, radiotherapy or topical therapies, in the patient‐level and the tumour‐level analyses, despite histological‐type and pretreatment. Relapse of BCC may be a low life‐threatening risk, and there are merits of non‐surgical treatment. However, the significant difference in the recurrence rate is essential. Our study can provide useful guidance to clinicians in selecting treatment options for BCC.     

Relationship Between Calcium Intake and Impaired Activities of Daily Living in a Japanese Population: NIPPON DATA90

BackgroundMajor reasons for long-term care insurance certification in Japan are stroke, dementia, and fracture. These diseases are reported to be associated with calcium intake. This study examined the association between calcium intake and impaired activities of daily living (ADL) using the data from NIPPON DATA90, consisting of representative sample of the Japanese population.MethodsA population-based nested case-control study was performed. A baseline survey was conducted in 1990, followed by ADL surveys of individuals ≥65 years old in 2000. Individuals with impaired ADL and selected age- and sex-matched controls were then identified. We obtained 132 pairs. Calcium intake was energy-adjusted using the residual method. The association between calcium intake and impaired ADL was examined using conditional logistic regression models. To assess the accuracy of the estimates, we conducted bootstrap analyses.ResultsThe adjusted odds ratios (ORs) for impaired ADL compared with the group with a calcium intake of <476 mg/day were 0.72 (95% confidence interval [CI], 0.37–1.40) for the 476–606 mg/day group and 0.44 (95% CI, 0.21–0.94) for the ≥607 mg/day group in 2000 (P for linear trend = 0.03). After the bootstrap analyses, the inverse relationship unchanged (median OR per 100-mg rise in calcium intake, 0.87 [1,000 resamplings]; 95% CI, 0.76–0.97).ConclusionsAfter bootstrap analyses, calcium intake was inversely associated with impaired ADL 10 years after the baseline survey.Key words: bootstrap analyses, calcium intake, impaired activities of daily living, nested case-control study, NIPPON DATA90     

Protease‐activated receptor‐2 accelerates intestinal tumor formation through activation of nuclear factor‐κB signaling and tumor angiogenesis in ApcMin/+ mice

Hepatocyte growth factor activator inhibitor‐1 (HAI‐1), encoded by the SPINT1 gene, is a membrane‐bound protease inhibitor expressed on the surface of epithelial cells. Hepatocyte growth factor activator inhibitor‐1 regulates type II transmembrane serine proteases that activate protease‐activated receptor‐2 (PAR‐2). We previously reported that deletion of Spint1 in Apc^Min/+ mice resulted in accelerated formation of intestinal tumors, possibly through enhanced nuclear factor‐κB signaling. In this study, we examined the role of PAR‐2 in accelerating tumor formation in the Apc^Min/+ model in the presence or absence of Spint1. We observed that knockout of the F2rl1 gene, encoding PAR‐2, not only eliminated the enhanced formation of intestinal tumors caused by Spint1 deletion, but also reduced tumor formation in the presence of Spint1. Exacerbation of anemia and weight loss associated with HAI‐1 deficiency was also normalized by compound deficiency of PAR‐2. Mechanistically, signaling triggered by deregulated protease activities increased nuclear translocation of RelA/p65, vascular endothelial growth factor expression, and vascular density in Apc^Min/+‐induced intestinal tumors. These results suggest that serine proteases promote intestinal carcinogenesis through activation of PAR‐2, and that HAI‐1 plays a critical tumor suppressor role as an inhibitor of matriptase, kallikreins, and other PAR‐2 activating proteases.