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.     

Pediatric cerebral ganglioneuroblastoma

We describe a 4-year-old girl with acute onset headaches and transient blindness who underwent surgical intervention, chemotherapy, and radiotherapy for an intracranial mass. This mass was pathologically confirmed as a primary intracranial ganglioneuroblastoma, a rare finding in the pediatric population. The literature on pediatric primary intracranial ganglioneuroblastoma is reviewed.     

HIV Infection,Sexual Behaviors,Sexual Networks,and Drug Use Among Rural Residents in Yunnan Province,China

This cross-sectional study examined HIV prevalence, sexual behaviors, sexual networks, and drug use among 591 participants from a rural community in Yunnan Province, China. Face-to-face interviews were conducted to collect information about sexual behavior, drug use, and sexual networks. Blood samples were collected and tested for HIV. Of the participants, 52.6% were male and 62.6% were Jingpo minority. The HIV prevalence was 5.5% overall and highest among the Jingpo minority (7.7%). Most participants were sexually experienced and 32.5% had had multiple sex partners. About 18.8% had used drugs, with the highest proportion among the Jingpo minority. HIV infection was independently correlated with drug use among males and with multiple sexual partnerships among females. A total of 336 independent sexual network components (mostly small, linear, and acyclic) were constructed. Eighty-percent were dyads involving two members and 20% involved three to 71 members. Coupled with the promotion of condom use, gender- and network-specific efforts are needed for HIV prevention targeting ethnic minorities in Yunnan.     

NOS1 and SNAP25 polymorphisms are associated with Attention-Deficit/Hyperactivity Disorder symptoms in adults but not in children

Several investigations documented that Attention-Deficit/Hyperactivity Disorder (ADHD) is better conceptualized as a dimensional disorder. At the same time, the disorder seems to have different neurobiological underpinnings and phenotypic presentation in children compared to adults. Neurodevelopmental genes could explain, at least partly these differences. The aim of the present study was to examine possible associations between polymorphisms in SNAP25, MAP1B and NOS1 genes and ADHD symptoms in Brazilian samples of children/adolescents and adults with ADHD. The youth sample consisted of 301 patients whereas the adult sample comprises 485 individuals with ADHD. Diagnoses of ADHD and comorbidities were based on the Diagnostic and Statistical Manual of Mental Disorders–4th edition criteria. The Swanson, Nolan and Pelham Scale-Version IV (SNAP-IV) was applied by psychiatrists blinded to genotype. The total SNAP-IV scores were compared between genotypes. Impulsivity SNAP-IV scores were also compared according to NOS1 genotypes. Adult patients homozygous for the C allele at SNAP25 rs8636 showed significantly higher total SNAP-IV scores (F = 11.215; adjusted P-value = 0.004). Impulsivity SNAP-IV scores were also significantly different according to NOS1 rs478597 polymorphisms in adults with ADHD (F = 6.282; adjusted P-value = 0.026). These associations were not observed in children and adolescents with ADHD. These results suggest that SNAP25 and NOS1 genotypes influence ADHD symptoms only in adults with ADHD. Our study corroborates previous evidences for differences in the genetic contribution to adult ADHD compared with childhood ADHD.     

IL-6 receptor blockade ameliorates diabetic nephropathy via inhibiting inflammasome in mice

Background and ObjectiveInterleukin 6 (IL-6) has been identified as a key mediator in inflammation, immune responses and glucose metabolism. In this study, we assessed the effects of an IL-6 receptor antibody on diabetic nephropathy in a mouse model of type 2 diabetes mellitus.MethodsTwelve week old male db/db mice were treated with Tocilizumab (an IL-6 receptor antibody), normal IgG1 control antibody, insulin or normal saline for 12 weeks. Renal injury, inflammation and insulin resistance were assessed.ResultsDb/db mice treated with Tocilizumab exhibited reduced proteinuria and glomerular mesangial matrix accumulation compared to db/db + IgG controls. Additionally, Tocilizumab suppressed inflammatory response, oxidative stress and the IL-6 signaling pathway in the diabetic kidneys. It is noteworthy that blockade of IL-6 receptor blunted the activation of NLRP3 inflammasome partly through inhibition of IL-17A. Furthermore, insulin resistance assessed by glucose tolerance test, was ameliorated by Tocilizumab treatment.ConclusionsThe protective effects of an IL-6 receptor blockade against diabetic renal injury may be due to decreased insulin resistance and inhibition of the inflammasome.     

单中心乳腺癌术后乳房重建的影响因素

背景与目的：乳腺癌手术方式的选择受到诸多因素影响，本研究旨在分析乳腺癌患者选择乳房重建手术的影响因素，重点探讨居住地距离与乳房重建的关系。方法：回顾性分析了1999年1月—2015年12月复旦大学附属肿瘤医院收治的因单侧或双侧0～Ⅱ期乳腺癌行全乳切除术的女性患者临床资料，分析居住地距离与乳房重建比例的关系。结果：非上海患者选择全乳切除术后乳房重建比例高于上海患者(6.1% vs 4.5%，P<0.001)。居住地距离影响乳房重建比例(P=0.035)。单因素分析显示，居住地距离越远，选择乳房重建手术比例越高，而年龄、体质量指数(body mass index，BMI)、TNM分期与乳房重建的选择呈负相关(P均<0.001)。多因素分析显示，年龄增长、BMI增加、TNM分期较晚是拒绝行乳房重建的独立影响因素(P均<0.001)，而居住地距离不是乳房重建的独立影响因素(P>0.05)，且与具体乳房重建方式无交互作用。年龄与居住地距离呈负相关(P<0.001)。结论：乳腺癌患者的居住地距离与乳房重建比例呈线性相关；年龄、BMI和疾病分期是影响乳房重建的主要因素。     

The case for aflatoxins in the causal chain of gallbladder cancer

Chronic aflatoxin exposure has long been related to hepatocellular carcinoma (HCC). Recently, its association with gallbladder cancer (GBC) was postulated. Here we present the data supporting this hypothesis in Chile, the country with the highest GBC mortality worldwide with age-standardized mortality rates (ASMR) of 10.3 in women and 5.04 in men.The highest GBC rates occur in Southern Chile (ASMR = 18), characterized by: high Amerindian ancestry, associated with high bile acid synthesis and gallstones; high poverty and high cereal agriculture, both associated with aflatoxin exposure. Aflatoxins have been detected in imported and locally grown foods items. We estimated population dietary exposure ranging from 0.25 to 35.0 ng/kg-body weight/day. The only report on human exposure in Chile found significantly more aflatoxin biomarkers in GBC than in controls (Odds Ratio = 13.0).The hypothesis of aflatoxin-GBC causal link in the Chilean population is supported by: genetically-determined rapid cholesterol excretion and high gallstones prevalence (49.4%); low prevalence of HCC (ASMR = 4.9) and low HBV infection (0.15%) the main co-factor of aflatoxins in HCC risk.If the association between aflatoxins and GBC were confirmed, public health interventions based on food regulation could have a substantial public health impact.     

30例胸腺样分化甲状腺癌的回顾性分析及其机制研究

背景与目的：胸腺样分化甲状腺癌（carcinoma showing thymus-like differentiation，CASTLE）是非常罕见的甲状腺癌病理学类型，目前报道较少，相关诊疗经验及对该疾病的认知仍不足。方法：回顾并分析2007年9月1日—2021年9月1日复旦大学附属肿瘤医院收治的30例CASTLE患者的临床、病理学及预后资料。全基因组测序分析3例甲状腺癌及癌旁组织，转染构建MSH2过表达细胞株，并进行蛋白质印迹法（Western blot）、细胞活性及迁移实验等检测突变基因对细胞生物学行为的影响。结果：30例患者中，66.7%（20/30）的患者出现不同程度的外侵。平均随访60.6个月后，2例发生远处转移，无局部复发、进展或死亡病例。CD5、CD117呈阳性能对其进行有效的鉴别诊断。同时通过全基因检测和全基因组测序识别到MSH2、FBXW7及NOTCH1存在外显子突变，其中MSH2突变率最高，且可能参与提升甲状腺癌细胞的增殖及转移能力。结论：CASTLE恶性程度较低，进展缓慢，预后较好。根治性手术是CASTLE的首选治疗方式，术后放疗可能对减少局部复发有一定作用。MSH2基因可能参与CASTLE的发生、发展过程。