血清HE4水平对预测卵巢癌铂类化疗效果的临床观察

目的:探讨卵巢上皮癌患者血清中人附睾蛋白4(HE4)的水平与患者铂类化疗效果的关系。方法:回顾分析52例卵巢上皮癌患者的临床资料和随访信息,采用电化学发光法检测患者治疗前和随访时血清HE4及CA125水平,分析血清HE4及CA125水平与铂类化疗效果的关系。结果:52例患者中,31例铂类化疗敏感,21例铂类化疗抵抗。铂类化疗抵抗组患者治疗前血清HE4及CA125水平明显高于铂类化疗敏感组。治疗前血清HE4水平对卵巢癌铂类化疗疗效的预测效能高于CA125。铂类化疗抵抗组患者随访时血清HE4水平明显高于铂类化疗敏感组(276.5pmo/L vs 56.38pmo/L,P0.001)。随访时血清HE4可预测铂类化疗效果,当界值点为127.40pmo/L时,灵敏度达81%,特异度达93.5%,阳性预测值(PPV)为89.5%,阴性预测值(NPV)为87.9%,曲线下面积(AUC)为0.919。随访时血清CA125取界值点为76.4U/L时预测铂类化疗效果的灵敏度为95.2%,特异度为90.3%,PPV为85%,NPV为87.5%,AUC为0.876。随访时血清HE4预测铂类化疗效果的AUC也大于CA125。Logistic多因素回归分析结果显示,随访时血清HE4水平与发生铂类化疗抵抗密切相关(P=0.027)。结论:随访时血清HE4水平可以预测卵巢癌铂类化疗的反应。     

Micro coulter counters with platinum black electroplated electrodes for human blood cell sensing

We demonstrated a novel micro Coulter counter featuring platinum-black electrodes for human blood cell counting application. Two designs of micro Coulter counter were fabricated using two distinct technologies: integrated parylene and soft lithography. Platinum-black enhanced detection in the intermediate frequency range (∼100 Hz to 7 MHz), which is the operation frequency suitable for sensing the cells flowing by the electrodes. A detailed theoretical modeling of the sensing mechanism has been performed for the design of the electrodes, and electrical impedance spectra measurements confirmed the theoretical model. The surface morphology and roughness of the platinum black electroplated surface were characterized by SEM and AFM measurements. Polystyrene beads of various sizes were initially used to validate the operation of the devices, and using excitation frequency of 10 kHz, the signal magnitude was found to be correlated with the volume of the individual bead. Human blood cell sensing was successfully demonstrated with diluted whole blood and leukocyte rich plasma under the same excitation frequency. The histogram of impedance magnitude of the cells matched well with volume distributions of erythrocytes and leukocytes measured by conventional counting techniques. Micro Coulter counters have the advantages of small foot-print, low sample volume, and reduced cost of operation. Further development of the devices can lead to the development of a highly-sensitive and high-throughput handheld blood counting system for point-of-care applications.     

紫杉醇联合铂类治疗持续耐药及复发性妊娠滋养细胞肿瘤的疗效分析

目的:评价紫杉醇联合铂类药物化疗方案治疗持续耐药及复发性妊娠滋养细胞肿瘤(GTN)患者的疗效及安全性。方法:回顾性分析2006年1月至2013年1月,在北京协和医院接受紫杉醇联合铂类化疗方案治疗的25例持续耐药及复发性GTN患者的治疗情况及最终治疗结局。结果:25例持续耐药及复发性GTN患者共接受了115疗程的紫杉醇联合铂类的化疗方案,平均每例4.6±2.2(2~10)疗程,具体包括紫杉醇+顺铂(TP)方案52疗程、紫杉醇+卡铂(TC)方案56疗程及紫杉醇+依托泊苷/紫杉醇+顺铂(TE/TP)方案7疗程。在停止化疗时,血清学完全缓解14例,部分缓解4例,治疗无效7例,完全缓解率为56.0%(14/25),总缓解率为72.0%(18/25),血清学完全缓解后的复发率为35.7%(5/14),平均复发时间为95.4±18.4天(约3.2个月)。紫杉醇联合铂类方案的毒副反应主要为骨髓抑制、消化道反应、肝肾损伤及过敏等,发生Ⅲ~Ⅳ度骨髓抑制患者比例为48.0%,未发生致死性副反应。结论:紫杉醇联合铂类对持续耐药及复发性GTN患者是可供选择的化疗方案。     

Oxaliplatin salvage for recurrent ovarian cancer: A single institution's experience in patient populations with platinum resistant disease or a history of platinum hypersensitivity

Objective

Hypersensitivity reactions can preclude platinum re-challenge for patients receiving second-line and higher carboplatin/cisplatin salvage therapy. The objective is to report our patient experience with oxaliplatin in recurrent or progressive epithelial ovarian (EOC), primary peritoneal (PPC) or fallopian tube cancer (FTC), including those with prior hypersensitivity reaction.

Methods

A single institution, retrospective review from 1995 to 2012 of patients receiving oxaliplatin for treatment of recurrent or progressive EOC, PPC, or FTC was performed. Data collected included patient demographics, diagnosis date, prior chemotherapy regimens, platinum-free interval(s), prior hypersensitivity reactions, oxaliplatin toxicity, length of therapy, disease response, and last follow-up. Those who received ≥ 1 cycles were included. A response to therapy was determined after ≥ 2 cycles.

Results

Forty-four patients were identified. All had prior carboplatin and 38.6% had prior cisplatin therapy. Twenty-three had a prior platinum hypersensitivity reaction. Patients received a median of 2 prior platinum containing regimens and 5 chemotherapy lines prior to oxaliplatin exposure. One patient experienced grade 3 pain. No grade 4 toxicities occurred. No treatment delays for pancytopenia noted. Nausea and dysesthesias were controlled medically and weren't dose-limiting. No nephropathy or neuropathy progressed on oxaliplatin or were dose-limiting. Disease response was observed in 43.2%. Of the responders, 36.8% had a prior platinum hypersensitivity reaction. Median number of 5 cycles of an oxaliplatin containing regimen was given. Median follow-up was 15.5 months.

Conclusions

In our experience, oxaliplatin is well tolerated and should be considered for platinum challenge after hypersensitivity even in patients with platinum resistant disease with a reasonable chance of response.     

晚期非小细胞肺癌组织中ERCC1、RRM1表达水平与含铂治疗方案疗效及预后相关性分析

目的：探讨ERCC1及RRM1的表达在预测晚期非小细胞肺癌含铂治疗方案疗效及预后中的作用。方法：用免疫组织化学的方法检测124例ⅢB和Ⅳ期非小细胞肺癌患者的石蜡包埋活检组织标本中ERCC1和RRM1的表达水平,并分析其与临床病理特征以及疗效、预后的相关性。124例均为接受以铂类为基础的三代药物联合化疗的初治患者。结果：ERCC1、RRM1表达阳性者分别为43例（35％）和50例（40％）。ERCC1及RRM1的表达与疗效相关,ERCC1表达阴性者疗效达PR的患者（54％）明显高于阳性者（33％）,差异有统计学意义（P=0．022）。同样,RRM1表达阴性患者疗效为PR的明显高于RRM1阳性者（53％VS34％,P=0．042）。ERCC1和RRM1同时阴性表达者的中位生存时问明显长于同时阳性表达者（11．7个月VS9．2个月,P=0．025）,多因素分析表明,ERCC1为独立的预后预测因素（P=0．0066）。结论：ERCC1的表达与晚期非小细胞肺癌预后及含铂治疗方案疗效相关。     

Platinum levels in various tissues of a patient who died 181 days after cisplatin overdosing determined by electrospray ionization mass spectrometry

Platinum (Pt) levels were determined in various tissues and body fluids obtained from a patient who died 181 days after cisplatin overdosing. The symptoms of cisplatin overdose, however, might have almost disappeared by day 40, and the patient’s death was ascribed to the recurrence of malignant lymphoma. Determination of Pt derived from cisplatin was performed by electrospray ionization mass spectrometry (ESI-MS) using silver (Ag) as internal standard. Pt and Ag complexed with diethyldithiocarbamate (DDC) in wetashed blood, and tissue solutions were extracted into isoamyl alcohol, and then acidified with oxalic acid. By injecting an aliquot of the isoamyl alcohol layer into a mass spectrometer in the direct flow injection mode, the quantitation was performed using the signals of Pt(DDC)₃ ⁺ and Ag(DDC)₂ ⁺ at m/z 639 and 403, respectively. The Pt levels ranged from 25ng/ml in blood to 2050ng/g wet weight in the liver of the patient, indicating that Pt remained at high levels in tissues, even after a period as long as 181 days after cisplatin overdosing.     

Developmental validation of the Huaxia™ Platinum PCR amplification kit: A 6-dye multiplex direct amplification assay designed for Chinese reference samples

The Huaxia™ Platinum Kit for short tandem repeat (STR) amplification was designed to meet the needs of the rapidly growing Chinese forensic database. This PCR multiplex allows simultaneous amplification of the following autosomal loci: D3S1358, vWA, D16S539, CSF1PO, TPOX, D8S1179, D21S11, D18S51, Penta E, D2S441, D19S433, TH01, FGA, D22S1045, D5S818, D13S317, D7S820, D6S1043, D10S1248, D1S1656, D12S391, D2S1338, Penta D and the gender-identification markers Yindel, and AMEL.The Huaxia™ Platinum Kit enables direct amplification from blood and buccal samples stored on treated and untreated paper, and features an optimized PCR protocol that yields time to results in less than 45 min. Developmental validation testing followed SWGDAM guidelines and demonstrated that this assay produces reproducible and accurate results. Studies on 798 individuals in 4 major Chinese ethnic groups produced highly concordant results with other commercially available STR genotyping kits. The validation results demonstrate that the Huaxia™ Platinum Kit is a robust and reliable identification system for forensic DNA databasing applications.     

铂金弹簧圈与 HydroCoil 治疗未破裂颅内动脉瘤的疗效比较

目的 评价铂金弹簧圈与 HydroCoil 治疗未破裂颅内动脉瘤的疗效。方法 选择2011年4月～2015年4月在本院就诊的未破裂脑动脉瘤患者78例,随机分为水凝胶弹簧圈(HES)组40例和铂金弹簧圈(BPC)组38例,分别采用HES和BPC进行血管栓塞术,评价2组术后动脉瘤栓塞程度、栓塞密度弹簧圈使用数量和12个月后动脉瘤复发情况,并记录相关并发症。结果 HES组和BPC组完全栓塞率分别为84.21%(32/38)和75.00%(30/40),栓塞密度为0.329±0.143和0.668±0.227,组间比较均无明显差异(P>0.05); HES组达到完全栓塞所需要的弹簧圈少于BPC组(P<0.05); 2组并发症发生率分别为13.16%(5/38)和5.00%(2/40),组间比较无明显差异(χ²=1.588,P=0.208); 随访12个月后2组分别有35例和37例患者完成随访,复发率为14.29%(5/35)和18.92%(7/37),组间比较无明显差异(P>0.05); logistic回归分析表明只有血管瘤直径是复发的独立相关因素(P<0.05)。结论 HES治疗未破裂脑动脉瘤的完全栓塞率和远期复发率不能优于BPC组,而且价格高于BPC,不推荐HES作为首选方法。     

泰素联合铂类一线治疗老年晚期非小细胞肺癌的临床研究

背景与目的 非小细胞肺癌(NSCLC)系老年性疾病.老年患者往往不作为铂类化疗的适用者,然而近年许多临床研究表明,年龄因素不是影响老年患者化疗的绝对禁忌证.本研究目的在于评价泰素联合铂类化疗方案一线治疗晚期≥60岁老年与＜60岁较年轻非小细胞肺癌患者中的近期疗效、毒性反应、疾病进展时间和总生存时间.方法 2000年9月-2005年9月共192例初治晚期非小细胞肺癌患者入组.按年龄分为≥60岁组(94例)和＜60岁组(98例),ECOG评分0-2分.治疗方案:泰素175 mg/m2,d1,顺铂75 mg/m2,d1,卡铂(AUC=5),d1,3～4周重复.结果 ≥60岁组和＜60岁组的客观有效率分别为22.34%和24.49%(P=0.710);中位疾病进展时间分别为4.1个月和4.4个月(P=0.085);中位生存期分别为11.8个月和12.4个月(P=0.08),差异均无统计学意义.毒副反应为血液学毒性和非血液性毒性:3/4级白细胞、血小板下降发生率两组比较,P值分别为0.863及0.057,差异无统计学意义.非血液学毒性主要为脱发、恶心,呕吐反应、关节肌肉酸痛、肢端麻木、乏力等,但以1/级多见.结论 泰素联合铂类化疗方案在老年人晚期NSCLC中疗效较好,毒副反应可耐受,值得临床进一步推广.