Expression and association of CD44v6 with prognosis in T2-3N0M0 esophageal squamous cell carcinoma

Aim

To investigate the expression of CD44v6 in stage T2-3N0M0 esophageal squamous cell carcinoma (ESCC) and its prognostic significance.

Methods

The expression of CD44v6 in a series of 227 ESCC specimens was evaluated by immunohistochemistry (IHC). A reproducible semiquantitative method which took both staining percentage and intensity into account was applied for IHC scoring, and receiver operating characteristic (ROC) curve analysis was utilized to select the cut-off score for high or low IHC reactivity. Then, the correlations of CD44v6 expression with clinicopathological features of patients and its prognostic relevance were determined.

Results

In the present study, the proportion of low CD44v6 expression was found significantly lower in Grade 3 of ESCC, than that of Grade 1 and Grade 2 of ESCC. There are no significant correlations between CD44v6 expression and other clinicopathological parameters including gender, age, tumor size, tumor location, depth of invasion and pathological stage. The Kaplan-Meier survival curves showed that up-regulated expression of CD44v6 indicated a poorer post-operative survival for ESCC patients of stage T2-3N0M0 (P=0.009), especially for those with T2 lesions (P=0.044) or with stage IIB diseases (P=0.005). Multivariate analysis also confirmed that CD44v6 expression [relative risk, 1.639; 95% confidence interval (CI): 1.142-2.354, P=0.007] and depth of invasion (relative risk, 1.487; 95% CI: 1.063-2.080, P=0.020) were independent prognostic factors.

Conclusions

Elevated CD44v6 expression may be an adverse prognostic indicator for patients with stage T2-3N0M0 ESCC, especially for those with T2 lesions or stage IIB diseases.     

A study of weekly docetaxel and carboplatin as first-line chemotherapy for advanced non-small cell lung cancer

Background

Weekly docetaxel demonstrated similar efficacy but better tolerability than standard triweekly docetaxel, and carboplatin was less nephrotoxic, neurotoxic and emetogenic than cisplatin. This study aimed to evaluate the efficacy and safety of weekly docetaxel with carboplatin as first-line chemotherapy for advanced non-small cell lung cancer (NSCLC).

Methods

Forty-three Chinese patients have been included. Patients were administered docetaxel at a dose of 35 mg/m² on days 1, 8, 15 and carboplatin at an area under the curve (AUC) 5 on day 1 every 28-day cycle (maximum six cycles).

Results

Of the 43 eligible patients, the assessed overall response rate (RR) was 30.2% with 30.2% partial response (PR) in 13 patients, 48.8% stable disease (SD) in 21 patients and 20.9% progressive disease (PD) in 9 patients. The estimated median progression free survival and median overall survival (OS) time were respectively, 120 days (95% CI: 80-160 days) and 340 days (95% CI: 224-456 days) with the patients surviving of 46.5% (95% CI: 31.6-61.4%) at one year and 20.0% (95% CI: 7.1-33.3%) at two years. The major grade 3/4 hematological toxicities were included leucocytopenia in 6 patients (13.9%) and neutropenia in 8 patients (18.6%). One patient (2.3%) suffered grade 1 febrile neutropenia. All grade of the nonhematological toxicities, such as nausea, vomiting, alopecia and fatigue held the proportion of 48.8% (grade 3/4 4.6%), 27.9%, 55.8% and 53.5% (grade 3/4 9.3%), respectively.

Conclusions

The combination of weekly docetaxel and carboplatin showed feasible efficacy with acceptable hematologic toxicities for advanced lung cancer.     

短暂性脑缺血发作及小卒中早期进展的风险评估

目的分析短暂性脑缺血发作(TIA)及小卒中早期进展的危险因素。方法回顾性分析448例TIA或小卒中患者的入院资料,随访发病后7、30及90 d脑梗死发生率/复发率,通过Logistic回归分析TIA/小卒中随访期间新发脑梗死的危险因素。结果 TIA/小卒中患者7、30及90 d内新发脑梗死率分别为26.3%、30.1%、36.8%;直线回归分析显示ABCD2-DI评分与TIA/小卒中早期新发脑梗死呈正相关关系。Logistic回归分析TIA/小卒中患者7、30及90 d新发脑梗死的危险因素为:ABCD2-DI评分(OR值分别为2.23、3.03、5.24,P均0.05);糖化血红蛋白(OR值分别为1.71、2.56、3.44,P均0.05);双联抗血小板药物治疗(OR值分别为0.42、0.39、0.26,P均0.01);高敏CRP与7 d内新发脑梗死的OR值为1.58,P0.05。结论 ABCD2-DI评分、高敏CRP、糖化血红蛋白是TIA/小卒中患者早期进展的独立危险因素,使用双联抗血小板药物治疗可能是TIA/小卒中早期进展的保护因素。     

甘氨酸龈下喷砂联合引导组织再生术治疗种植体周围炎

目的探讨甘氨酸龈下喷砂联合引导组织再生术（GTR）治疗种植体周围炎的有效性。 方法28例伴有牙槽骨吸收的种植体周围炎患者,按照随机、双盲、对照原则将种植体（共34枚）分成2组,分别行GTR,其中试验组（n= 18）在术中使用甘氨酸龈下喷砂系统对种植体表面进行清创;对照组（n= 16）采用塑料刮治器对种植体表面进行清创。在治疗前（基线）、治疗后3个月、治疗后6个月和治疗后12个月进行临床指标的检测,包括菌斑指数（PLI）、出血指数（BI）、探诊深度（PD）、临床附着水平（CAL）及影像学垂直骨增量。数据采用重复测量资料的方差分析,每个时间点采用独立样本t检验进行分析,试验组和对照组分别进行治疗前与治疗后的自身对比,并在基线、治疗后3个月、治疗后6个月和治疗后12个月进行临床指标的组间对比,以P<0.05为差异有统计学意义。 结果在基线,试验组和对照组各临床指标差异无统计学意义（P>0.05）。各组术后PLI、BI、PD、CAL及影像学垂直骨增量均较治疗前（基线）有明显改善,差异有统计学意义（P<0.05）。患者治疗后3个月,试验组与对照组BI、PLI、PD、CAL差异均有统计学意义（t_BI= 5.103,P_BI= 0.031;t_PLI= 5.556,P_PLI= 0.025;t_PD= 4.440,P_PD= 0.043;t_CAL= 4.879,P_CAL= 0.034）。患者治疗后6个月,试验组和对照组的PD、CAL差异均有统计学意义（t_PD= 4.994,P_PD= 0.033;t_CAL= 4.831,P_CAL= 0.035）。患者治疗后12个月,试验组和对照组的PD、CAL差异均有统计学意义（t_PD= 4.302,P_PD= 0.046;t_CAL= 4.325,P_CAL= 0.048）。患者治疗后6及12个月,试验组与对照组种植体的PLI和BI均有改善,但差异无统计学意义（P>0.05）。患者影像学垂直骨增量在治疗后3、6、12个月试验组较对照组增加更明显,差异均有统计学意义（t₃=4.831,P₃= 0.035;t₆= 4.412,P₆= 0.044;t₁₂= 5.087,P₁₂= 0.031）。 结论在改善种植体周围炎炎症水平及促进牙槽骨再生方面,甘氨酸龈下喷砂联合GTR较机械刮治联合GTR更具优势,可考虑在GTR中使用甘氨酸龈下喷砂来提高种植体周围炎的治疗效果。     

Blood–spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice

Humans with ALS and transgenic rodents expressing ALS-associated superoxide dismutase (SOD1) mutations develop spontaneous blood–spinal cord barrier (BSCB) breakdown, causing microvascular spinal-cord lesions. The role of BSCB breakdown in ALS disease pathogenesis in humans and mice remains, however, unclear, although chronic blood–brain barrier opening has been shown to facilitate accumulation of toxic blood-derived products in the central nervous system, resulting in secondary neurodegenerative changes. By repairing the BSCB and/or removing the BSCB-derived injurious stimuli, we now identify that accumulation of blood-derived neurotoxic hemoglobin and iron in the spinal cord leads to early motor-neuron degeneration in SOD1^G93A mice at least in part through iron-dependent oxidant stress. Using spontaneous or warfarin-accelerated microvascular lesions, motor-neuron dysfunction and injury were found to be proportional to the degree of BSCB disruption at early disease stages in SOD1^G93A mice. Early treatment with an activated protein C analog restored BSCB integrity that developed from spontaneous or warfarin-accelerated microvascular lesions in SOD1^G93A mice and eliminated neurotoxic hemoglobin and iron deposits. Restoration of BSCB integrity delayed onset of motor-neuron impairment and degeneration. Early chelation of blood-derived iron and antioxidant treatment mitigated early motor-neuronal injury. Our data suggest that BSCB breakdown contributes to early motor-neuron degeneration in ALS mice and that restoring BSCB integrity during an early disease phase retards the disease process.The blood–brain barrier (BBB) and blood–spinal cord barrier (BSCB) prevent entry of toxic circulating molecules and cells into the central nervous system (CNS) (1). Amyotrophic lateral sclerosis (ALS) is the most prominent adult motor-neuron disorder resulting in progressive motor-neuron loss in the spinal cord, brainstem, and motor cortex (2). Most ALS cases are sporadic (90%) whereas 10% are familial ALS. Over twenty independent studies in postmortem human tissue and cerebrospinal fluid (CSF) sampling from living ALS patients have established that the BBB and BSCB are damaged in familial and sporadic ALS, as reviewed elsewhere (1, 3). This BBB and BSCB disruption has been shown by spinal-cord and/or motor-cortex accumulation of different plasma proteins (e.g., IgG, fibrin, thrombin), erythrocytes, erythrocyte-derived hemoglobin and iron-containing hemosiderin, elevated CSF/serum albumin ratios, and diminished expression or degradation of the BSCB tight-junction proteins (1, 3–5). Deposition of hemoglobin-derived iron within the CNS has also been shown in ALS patients (3, 6, 7). Because human postmortem studies reflect, however, end-stage disease, it has remained unclear as to which stage of disease is enhanced by BSCB disruption. Longitudinal CSF or BSCB imaging studies have yet to be performed in living ALS patients (3) to clarify whether spinal-cord vascular dysfunction contributes to early- or late-stage disease.Transgenic rodents expressing human ALS-associated Cu/Zn superoxide dismutase (SOD1) mutations that represent 20% of all familial cases also develop a spontaneous BBB/BSCB disruption (8–12) similar to vascular pathology reported in humans (1, 3–7). Mice with a chronic BBB disruption due to aberrant signal transduction between the central nervous system endothelial cells and pericytes or astrocytes and pericytes develop a chronic BBB opening accompanied by accumulation of toxic blood-derived products in the central nervous system and secondary functional and structural neuronal changes (13–15).To determine whether BSCB disruption contributes to fatal paralytic disease caused by expression of an ALS-causing mutant, we now report how perturbing the BSCB, repairing the BSCB, and/or removing the BSCB-derived injurious stimuli influence development of disease in SOD1^G93A mice that develop a spontaneous BSCB breakdown (8, 9, 12).     

MR扩散加权成像纹理分析鉴别肝硬化背景下不典型强化的小肝癌和增生结节

目的探讨基于磁共振扩散加权成像(DWI)的纹理分析鉴别诊断肝硬化不典型强化小肝癌(sHCC)和增生结节(DNs)的价值。方法回顾性分析术前MRI动态增强不典型强化、手术标本病理学证实的单发肝硬化结节(≤2 cm)患者59例的资料,其中不典型强化sHCC 37例,DNs 22例。分析病灶的DWI信号特征,测量病灶的平均表观扩散系数(ADC)值、病灶与肝实质ADC比值。采用MaZda软件手工勾画感兴趣区,提取病灶DWI的纹理参数,采用Fisher系数、分类错误概率联合平均相关系数、交互信息三者联合的方法选择30个最佳纹理参数集合。使用原始数据分析、主要成分分析、线性判别分析和非线性判别分析进行纹理分类。采用独立样本t检验比较sHCC与DNs组间ADC值、ADC比值的差异,计数资料(或率)的比较采用χ2检验。采用ROC曲线分析评估诊断效能。结果DWI高信号鉴别不典型强化sHCC与DNs的灵敏度、特异度及准确度分别为94.6%(35/37)、68.2%(15/22)及84.7%(50/59)。不典型强化sHCC的ADC比值显著低于DNs,差异存在统计学意义(t=2.99,P=0.002);诊断不典型强化sHCC的灵敏度、特异度及准确度分别为73.0%(27/37)、72.7%(16/22)及72.9%(43/59)。DWI纹理分析诊断不典型强化sHCC的灵敏度、特异度及准确度为94.6%(35/37)、95.5%(21/22)及94.9%(56/59)。DWI纹理分析的诊断效能(AUC=0.94)显著高于DWI高信号(AUC=0.81)及ADC比值(AUC=0.72)。结论基于DWI的纹理分析可以鉴别肝硬化背景下不典型强化的小肝癌和增生结节,其效能优于定性及定量DWI。     

临床研究数据与安全监查国际发展现状与思考

数据与安全监查委员会（Data and Safety Monitoring Board,DSMB）在国际范围内广泛应用于大规模、多中心临床试验及政府资助项目,它在全程保护受试者安全、提升临床研究质量与水平方面起着十分重要的作用。虽然DSMB在欧美发达国家运用经验较成熟,但在我国目前尚处于起步阶段。该文通过回顾DSMB的起源和工作流程,比较模式及国际现行各指导原则,分析其应用现状、发展趋势和存在的问题,提出根据各国国情及不同临床研究特点,除了对累积数据进行期中分析以动态评估干预措施的安全性有效性外,采取扩大监查范围、丰富监查模式、建立专业的技术队伍、制定符合各类临床研究特点的DSMB操作规程、重视并建立DSMB保险和赔偿机制等策略,不仅是在国际范围内推进和完善数据与安全监查工作的有效途径,也是提高我国临床研究技术与国际先进水平接轨亟待解决的问题。