基于二代测序技术探究食管鳞癌分子生物学特征及临床意义

目的 利用二代测序技术(NGS)对基因突变频率进行分析,探究食管鳞癌(ESCC)基因突变特征,寻找潜在的靶向治疗和免疫治疗靶点。 方法 随机收集49例山东省立医院确诊的ESCC患者的石蜡肿瘤组织样本,进行DNA提取,采用Illumina HiSeq4000测序平台对416个肿瘤相关基因进行捕获测序,测序结果进行生物信息学分析。 结果 发现TP53基因突变频率最高,并发现了多个ESCC潜在治疗靶点。EGFR 19del突变率和扩增率均为4.08%,未见EGFR L858R突变及KRAS突变;HER2和MET基因扩增发生率均为2.04%;BRCA1/2基因失活突变率约为8.06%;另外,MSI阳性率约为4.76%。提示携带相关靶点突变的患者可能是靶向治疗或免疫治疗的潜在获益人群。 结论 通过高通量检测技术发现ESCC多个潜在治疗靶点,对患者临床治疗方案的制定有重要意义。     

Effect modification of general and central obesity by sex and age on cardiovascular outcomes: Targeted maximum likelihood estimation in the atherosclerosis risk in communities study

Background and aimsTo elucidate the effect modification of general and central obesity by sex and age on the risk of cardiovascular events.MethodsThe analysis included 14,983 males and females aged 45–75 years from the Atherosclerosis Risk in Communities study. Obesity was defined with body mass index (BMI), waist-to-hip ratio (WHR) and body shape index (BSI) which categorized the participants as obese and non-obese. Targeted maximum likelihood estimation was used to estimate the risk ratio (RR) with the tmle package in R software.ResultsAfter adjustment, the strongest effect of BMI on CHD was in females (RR (95%CI): 1.26 (1.11, 1.42)) and in age>54 (RR (95%CI): 1.16 (1.06, 1.27)) and for HF it was in age>54 (RR (95%CI): 1.18 (1.10, 1.26)) and in females (RR (95%CI): 1.17 (1.08, 1.28)). Regarding central obesity, WHR (RR (95%CI): 1.19 (1.05, 1.34)) had the strongest effects on CHD for males and BSI (RR (95%CI): 1.140 (1.02, 1.26)) for age ≤ 54, and for HF the WHR (RR (95%CI): 1.22 (1.10, 1.36)) and BSI (RR (95%CI): 1.18 (1.07, 1.30)) had the strongest effects for age≤54, respectively.ConclusionAmong males and age≤54, WHR index was associated with a higher risk of CHD and HF while BMI was so for females and age>54.     

负压封闭引流装置联合中厚皮片移植修复头皮缺损40例临床分析

目的分析负压封闭引流装置联合中厚游离皮片移植修复头皮缺损的效果。方法选取2013-06-2019-06间郑州大学第一附属医院收治的40例多种原因造成的头皮缺损患者为研究对象。均采用负压封闭引流装置联合中厚游离皮片移植修复头皮缺损。回顾性分析患者的临床资料。结果40例患者中,39例(97.5%)一次手术植皮成功,皮片成活良好。仅1例患者需行二次植皮手术。患者的满意度为100%。结论负压封闭引流装置联合中厚游离皮片移植治疗头皮缺损,皮片成活率高。     

Prolonged Survival of Patients With Non–Small-Cell Lung Cancer With Leptomeningeal Carcinomatosis in the Modern Treatment Era

IntroductionLeptomeningeal carcinomatosis (LM) is a severe complication of non–small-cell lung cancer (NSCLC) historically associated with poor prognosis. New chemotherapeutic and targeted treatments could potentially affect the natural history of LM.Patients and MethodsPatients with a pathologic diagnosis of NSCLC with LM treated at Stanford between 2003 and 2011 were identified via institutional databases and medical records. LM was defined by cerebrospinal fluid (CSF) that was positive for malignant cells or by LM enhancement on magnetic resonance imaging with gadolinium contrast. Retrospective, landmark analyses were performed to estimate survival. Statistical analyses were performed using SAS Enterprise Guide, version 4.3.ResultsLM was identified in 30 patients. All cases were adenocarcinoma; 60% of patients had a known or suspected driver mutation. The mean age was 58 years. Of the 30 patients, 67% were women; 70% were nonsmokers; 27% initially presented with LM; 84% received systemic treatment at or after development of LM; and 53% of these patients received modern systemic therapy for their LM, defined as a regimen containing pemetrexed, bevacizumab, or a tyrosine kinase inhibitor. Mean overall survival after LM diagnosis was 6 months (95% CI, 3-12). Patients who received modern systemic therapy for LM had decreased hazard of death (hazard ratio [HR], 0.24; P = .007).ConclusionIn this retrospective, single-institution analysis, median survival with LM was higher compared with historical experience. Patients who received modern systemic therapy for their LM had particularly good outcomes. These data provide evidence for improving survival outcomes in the modern treatment era for this difficult-to-treat complication.     

Carcinoma of Unknown Primary Site (CUP) With Metastatic Renal-Cell Carcinoma (mRCC) Histologic and Immunohistochemical Characteristics (CUP-mRCC): Results From Consecutive Patients Treated With Targeted Therapy and Review of Literature

Background

Carcinoma of unknown primary site (CUP) is a heterogenous group of metastatic cancer with no detectable primary tumor site. Diagnostic assessment occasionally presents CUP with metastatic renal-cell carcinoma (mRCC) histologic and immunohistochemical characteristics (CUP-mRCC). Efficacy and toxicity data for vascular endothelial growth factor inhibitor therapies in CUP-mRCC patients are few.

Novel Targeted Therapies for Chronic Lymphocytic Leukemia in Elderly Patients: A Systematic Review

Chronic lymphocytic leukemia (CLL) typically affects older patients; administration of traditional cytotoxic therapies in old patients has very modest benefit with no survival improvement. With better understanding of CLL biology, trends are shifting towards the use of targeted therapies. The objective of this article is to review the safety and efficacy of various novel agents that specifically target the dysregulated pathways, with particular attention to elderly patients. Agents like B-cell receptor (BCR) inhibitors (Bruton’s tyrosine kinase inhibitors [ibrutinib]), phosphatidylinositol 3-kinase inhibitors (idelalisib), spleen tyrosine kinase inhibitors (entospletinib), Bcl-2 inhibitors (venetoclax), immunomodulators (lenalidomide), and monoclonal antibodies (obinutuzumab, ofatumumab) have shown activity in CLL with a very favorable toxicity profile. Newer agents have improved clinical outcomes, and have tolerable toxicity profiles in elderly patients, resulting in the treatment with individualized therapy approach for CLL.     

Current management of stage IV nasopharyngeal carcinoma without distant metastasis

Up to one in four patients with nasopharyngeal carcinoma present with non-metastatic stage IV disease (i.e. T4 or N3). Distinct failure patterns exist, despite the routine adoption of contemporary treatment modalities such as intensity modulated radiotherapy and systemic chemotherapy. Concurrent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy or induction chemotherapy followed by CCRT are commonly employed in this setting, with the latter emerging as the preferred option. Additionally, emerging radiation technologies like proton therapy has become available offering new opportunities for prevention of radiation-induced side effects. This article reviews not only the current treatment strategies, but also discusses novel ways to tackle this challenging disease with respect to the patterns of failure.     

持续封闭负压引流术治疗浆细胞性乳腺炎患者的临床疗效

目的 探讨持续封闭负压引流术(VSD)治疗浆细胞性乳腺炎患者的临床疗效。 方法 选择青海省中医院2017年2月至2020年2月收治的93例患者，随机分为观察组(n=47)与对照组(n=46)。对照组采用常规切开引流术，观察组采用VSD治疗。比较两组临床疗效、换药频率、创面闭合时间及住院时间、VAS评分及生活质量评分、乳房毁损率及复发率。 结果 观察组整体临床疗效及临床总有效率均高于对照组，差异有统计学意义(P<0.05)。观察组换药频率、创面闭合时间、住院时间均低于对照组(P＜0.001)。治疗后，两组VAS评分下降，生活质量评分升高，差异有统计学意义(P<0.05)；且观察组VAS评分低于对照组，生活质量评分高于对照组(P＜0.001)。观察组乳房毁损0例，对照组6例(13.04%)；疾病复发1例(2.13%)，低于对照组的9例(19.57%)(P=0.012，P=0.008)。 结论 VSD治疗PCM临床疗效显著，可有效改善患者的临床症状体征，减少换药频率、缩短创面闭合时间及住院时间，降低乳房毁损率及疾病复发率，有效缓解患者痛苦，提高其生活质量，值得推广应用。