Germline mutations in the VHL gene associated with 3 different renal lesions in a Chinese von Hippel-Lindau disease family

Von Hippel–Lindau (VHL) disease is a rare autosomal dominant inherited cancer syndrome that is characterized by hemangioblastomas in the central nervous system and retina, renal cell carcinoma and cysts, pancreatic tumors and cysts, and pheochromocytoma. The underlying gene in this disease is the VHL tumor suppressor gene. We characterized a family with 2 affected siblings. The brother and sister displayed VHL type 2B and type 2A features, respectively. Renal lesions in the brother exhibited 3 different phenotypes, including simple renal cysts, multilocular cystic renal cell carcinoma and clear cell renal cell carcinoma. The phenotypes of the 3 concurrent renal lesions were first reported in this study. Mutation detection of the VHL gene revealed 2 recurrent mutations, namely c.256C>T (p.P86S) and c.340 + 5G > C. The former was predicted to be deleterious and to destabilize the hydrophobic core and lead to VHL dysfunction; however, the latter was predicted to be a benign variant. Our findings provided new data for the genotype-phenotype of VHL diseases and elucidated the pathogenic mechanism with in silico analysis.     

Association between Helicobacter pylori infection and dementia

Dementia is the severe loss of global cognitive ability in a previously healthy person. This study examined the relationship between Helicobacter pylori infection (HP-I) and non-Alzheimer’s dementia (non-AD) using a nationwide population-based dataset. The International Classification of Diseases, Ninth Revision (ICD-9) codes for dementia were used to define dementia patients; in addition, we examined the association of dementia with other comorbidities. Patients aged ⩾40 years with newly diagnosed HP-I (ICD-9 code 041.86) during 1998–2010 were identified as the HP-I cohort. The comparison cohort consisted of people aged ⩾40 years without HP-I (non-HP-I) randomly selected from the database at a ratio of 1:4 in the same time period. The controls were frequency matched according to the age (every 5 years), sex, and index year of patients in the HP-I cohort. Follow-up was performed for all patients until the date of dementia diagnosis (ICD-9 codes 290.0–290.4, 294.1, 331.0–331.2), date of withdrawal from the Taiwanese National Health Insurance program, date of death, or until December 31 2010. Compared with patients without HP-I, HP-I patients were 1.60-fold (95% confidence interval [CI] 1.32–1.95) more likely to develop non-AD. There was no statistical association between HP-I and AD. The adjusted hazard ratio of dementia increased from 1.48 (95% CI 1.22–1.79) for patients who had HP-I once to 2.19 (95% CI 1.13–4.25) for patients who had HP-I two or more times. Our study revealed that HP-I may be a critical risk factor for the development of non-AD. Further investigation, including clinical trials, to examine the microbe–dementia connection may provide further proof of the association between HP-I and dementia.     

Metastatic chromophobe renal cell carcinoma treated with targeted therapies: A Renal Cross Channel Group study

BackgroundTreatment of non–clear cell renal cell carcinoma (RCC) remains controversial despite several recent prospective studies of targeted therapies (TT). Often Vascular Endothelial growth Factor (VEGF) and Mammalian Target of Rapamycin (mTOR) inhibitors are used, extrapolating the data from use of these agents in clear cell RCC.MethodsWe performed a retrospective data analysis within the Renal Cross Channel Group to determine metastatic chromophobe RCC (mChRCC) outcomes in the TT era. The end-points were overall response, overall survival (OS) and time to treatment failure (TTF). The two latter were estimated using the Kaplan–Meier method.Results91 mChRCC patients from 26 centres were included. Median follow-up from the date of first metastasis was 6.1 years (range: 0–13.9). Median OS was 37.9 months (95% confidence interval [CI]: 21.4–46.8) from the diagnosis of metastatic disease. Among the 61 patients who received TT, 50 (82%) were treated with anti-angiogenic (AA) and 11 with mTOR inhibitors. Median TTF and OS in patients receiving a first line of AA was 8.7 months (95% CI: 5.2–10.9) and 22.9 months (95% CI: 17.8–49.2) versus 1.9 months (95% CI: 1.0–6.0) and 3.2 months (95% CI: 2.3–not evaluable) with mTOR inhibitors, respectively. A stratified log-rank test was used to compare AA and mTOR inhibitors TT, while controlling the effect of the International Metastatic RCC Database Consortium risk group and no significant difference between AA and mTOR inhibitors was observed for TTF (p = 0.26) or for OS (p = 0.55).ConclusionWe report the largest retrospective cohort of patients with mChRCC treated with TT and no significant difference between AA and mTOR inhibitors was observed for TTF and OS.