伴有8号染色体四体异常的t(15;17)急性早幼粒细胞白血病实验诊断及临床分析

目的:报告首例伴有8号染色体四体(四体8)异常的t(15;17)急性早幼粒白血病(AML-M3a),并研究其形态学、细胞遗传学、免疫学及临床特点。方法:外周血及骨髓标本直接涂片观察其形态学改变;采用骨髓细胞24h短期培养法制备染色体标本,RHG显带技术进行核型分析;以筑巢式逆转录聚合酶链反应(nested-RT-PCR)技术检测PML-RARa融合基因转录本;以流式细胞术检测免疫表型。结果:外周血涂片中早幼粒细胞占65%,可见中晚幼粒细胞。骨髓涂片显示有核细胞增生明显活跃,粒系83.6%,其中早幼粒细胞占72.4%,胞浆内可见大量紫红色颗粒。染色体核型分析揭示核型为48,XY,+8,+8,t(15;17)(q22;q12)[16]/47,XY,+8,t(15;17)(qxx:q12)[3]/46,XY,t(15;17)(q22;q12)[1]。RT-PCR检测PML-RARa(+),白血病细胞免疫表型检测显示CD13(96.2%)、CD33(55.9%)、CYMPO(93.5%)阳性,其余抗原包括淋系抗原在内均为阴性。本例患者生存期只有10d。结论:本例四体8是t(15;17)的继发性改变,可能是三体8克隆进展的结果。伴有四体8的t(15;17)AML-M3预后差。     

伴有t(9;12)(q22;p13)易位的急性髓细胞白血病M2a

目的报告1例伴有t(9;12)(q22;p13)易位的急性髓细胞白血病M2a。方法患者骨髓细胞短期培养后按常规方法制备染色体,采用R显带技术进行染色体核型分析;以9号和12号整条染色体涂染探针对其进行染色体涂染检测。结果染色体核型和染色体涂染分析均证实该患者具有t(9;12)(q22;p13)克隆性染色体异常。结论t(9;12)(q22;p13)易位是急性髓细胞白血病M2a的一种新的临床遗传学类型。     

培美曲塞加奈达铂联合三维适形放疗同步序贯治疗局部晚期非小细胞肺癌的疗效观察

目的探讨培美曲塞加奈达铂联合三维适形放疗同步、序贯治疗局部晚期非小细胞肺癌的疗效、不良反应和生存情况。方法共入选54例患者,分为同步组(CCR)和序贯组(SCR)。每组各27例。同步组采用培美曲塞(Pemetrexed)500mg/m2,奈达铂(Nedaplatin)80mg/m2(PN方案),放疗第1、21、43天静脉滴注;放疗采用三维适形放疗(3D-CRT),2Gy/次,总剂量70Gy。序贯组予PN方案化疗2个周期后,再以同方案放疗。结果中位随访时间22.8个月。同步组vs序贯组,总有效率:77.6%vs 61.8%(P>0.05),中位无进展生存期分别为12.2个月(95%CI:8.5~14.9个月)vs 9.1个月(95%CI:6.4~11.8个月)(P>0.05),1年、2年和3年生存率分别为81.5%vs 66.7%,48.1%vs 40.7%,29.6%vs 22.2%(P>0.05),中位生存期20.5个月(95%CI:13.7~27.3个月)vs 17.3个月(95%CI:14.2~20.4个月)(P>0.05)。不良反应以放射性食管炎、放射性肺炎为主,两组的Ⅰ~Ⅱ级急性放射性食管炎、Ⅰ~Ⅱ级急性放射性肺炎发生率分别为70.3%vs 55.5%,62.9%vs 44.4%(P>0.05)。两组骨髓抑制、恶心呕吐、腹泻和黏膜炎多为Ⅰ~Ⅱ级(P>0.05)。结论培美曲塞加奈达铂与三维适形放疗同步、序贯治疗局部晚期非小细胞肺癌疗效好,不良反应可耐受。同步放化疗比序贯放化疗略有增加,值得进一步推广和研究。     

常规放疗、三维适形放疗联合化疗治疗局部晚期肺癌的疗效比较

目的评价三维适形放疗联合化疗（3D-CRT）治疗局部晚期非小细胞肺癌（NSCLC）的近期疗效和急性毒副反应。方法收集2002年4月至2005年12月晚期非小细胞肺癌患者100例,分为三维适形放疗＋化疗（A组）50例,常规放疗＋化疗（B组）50例。A、B组化疗方案相同,泰素135mg／时,顺铂70mg／前,第1、29、57天。A组三维适形放疗放射源为6MV-X线,2Gy／（次·d）,40Gy后缩野加量,总剂量DT66—70Gy。B组常规放疗。结果晚期非小细胞肺癌患者经3个月治疗后,Ⅰ、Ⅱ、Ⅲ期CT改变≥50％（11．1％、26．9％、76．9％）与CT改变消失（88．9％、73．3、7．7％）,两者比较有显著性差异（x^2=6．70,x^2=6．69,x^2=70．1,P〈0．01）;鳞癌3年生存率（60．8％）明显高于腺癌（50．0％）两者比较有显著性差异（x^2=4．10,P〈0．05）;A组有效率（78．0）％明显高于B组（66．0）％（x^2=4．23,P〈0．05）;A组2年生存率（48．0）％高于高于B组（34．0）％（x^2=4．29,P〈0．05）;鳞癌有效率（60．0％）高于腺癌（48．4％）（x^2=4．12,P〈0．05）;放射性肺炎、食道炎、白细胞减少发生率分别为19例（19．0％）、7例（9．0％）、10例（10．0％）。结论3D-CRT联合化疗能提高局部晚期非小细胞肺癌的近期疗效,且急性毒副反应无明显增加。     

Phase II study of oral trofosfamide as palliative therapy in pretreated patients with metastatic soft-tissue sarcoma.

This phase II study investigated the activity of continuously administered oral trofosfamide in chemotherapy-pretreated patients with metastatic soft-tissue sarcoma (STS). Trosfosfamide is an oxazaphosphorine with ifosfamide as the predominant metabolite. Eighteen patients with a median age of 60 years were treated with trofosfamide given as continuous oral treatment. Starting dose was 300 mg/day for 7 days and subsequently 150 mg/day. All patients had previously received at least one chemotherapy regimen including doxorubicin and ifosfamide. Three patients achieved partial responses (18%) and nine a disease stabilization (53%) for an overall response rate of 18% (95% CI: 0.5-35%). Median progression-free interval was 4 months (0-17 months) and median overall survival was 10 months (4-39+) months. Toxicity was generally mild. Only one WHO grade III nausea, but no other non-hematologic WHO grade III/IV toxicity occurred. Leukopenia WHO grade III/IV was observed in four patients (22%). No thrombocytopenia <50,000/microl and no neutropenic infection was seen. Continuously administered oral trofosfamide is a well-tolerated palliative treatment in anthracycline/oxazaphosphorin-pretreated patients with advanced STS achieving responses and/or disease stabilization in up to 70% of patients.     

高分级神经胶质瘤术后同期放化疗的疗效

目的:分析高分级神经胶质瘤术后调强放疗(IMRT)联合替莫唑胺化疗的疗效。方法:2005年1月-2009年12月共53例高分级神经胶质瘤术后患者接受IMRT联合替莫唑胺化疗。放疗方案为IM-RT,同期加量,PTV2处方剂量50.4 Gy/28f,PTV1处方剂量58.8 Gy/28f,PTVtb处方剂量61.6 Gy/28f,PGTV处方剂量64.4 Gy/28f。在放疗期间每天口服替莫唑胺75 mg.m-2。放疗结束休息4周后循环口服化疗,放疗后的第1个疗程每天口服150 mg.m-2,连续5 d,第2个疗程起改为每天口服200 mg.m-2,28 d为1个疗程,计划接受4个周期辅助化疗。记录治疗反应,计算总生存率和局部无进展生存率。结果:本组患者急性不良反应多为1～2级,无4级以上反应,有3例发生后期放射性脑损死。1,2和3年总生存率分别为75.5%,52.8%和39.6%,1,2和3年局部无进展生存率分别为67.9%,45.3%和35.8%。结论:术后IMRT联合替莫唑胺治疗高分级神经胶质瘤可以获得较为理想的临床疗效,治疗后急性不良反应轻微,晚期不良反应可接受。     

不均等分割放疗联合化疗治疗晚期鼻咽癌的效果

目的　观察不均等分割放射治疗联合化疗对晚期鼻咽癌的治疗效果。方法　 5 3例初治晚期鼻咽癌患者分为不均等分割放疗加化疗组 2 9例 (研究组 )和常规分割放疗加化疗组 2 4例 (常规组 )。常规组外照射 (面颈联合野 )DT3 6～ 4 0Gy/ 2 0F、4w后 ,研究组不均等分割放射 (双侧耳前野 )DT3 0～3 3Gy/ 3 0F、3w ,同期加照鼻前野 9Gy/ 6F、3w ,总剂量 75～ 82Gy/ 5 6F、7w ;常规组设双侧耳前野及鼻前野 ,三野交替 ,DT2 7～ 3 0Gy/ 15F、3w ,总剂量 63～ 70Gy/ 3 5F、7w ,两组的化疗方案相同。顺铂 (DDP)2 0mg/m2 ·d ,d1-3,5 氟尿嘧啶 ( 5 FU) 5 0 0mg/m2 ·d ,d1-5,放疗前 1周期、放疗后 2周期。结果　①研究组、常规组鼻咽肿瘤完全消退率分别为 93 .1%、75 .0 % (P <0 .0 5 ) ,颈淋巴结完全消退率分别为96.0 %、75 .0 % (P <0 .0 5 ) ;② 3年生存率两组分别为 82 .7%、70 .8% (P >0 .0 5 ) ;③急性粘膜反应及胃肠道反应两组相似。结论　不均等分割放疗联合DDP + 5 FU方案 ,能显著提高鼻咽部及颈淋巴肿瘤的消退率 ,对晚期鼻咽癌的局部控制率明显高于常规放疗加化疗 ,近期疗效较好 ,是治疗晚期鼻咽癌的有效方法。但 3年生存率无统计学差异 ,其不良反应相似。     

三维适形放疗同期化疗综合治疗局限期小细胞肺癌的临床观察

目的 评价三维适形放射治疗同期化疗综合治疗局限期小细胞肺癌的疗效及不良反应.方法 33例局限期小细胞肺癌患者行EP方案化疗,3周为1个周期,共行6个周期.放疗在化疗第1个周期或第3个周期同期进行,照射野包括原发病灶和纵隔,照射剂量45 Gy/3周,每次1.5 Gy.每天2次.结果 33例入组患者同期放化疗毒性可耐受.总有效率(CR+PR)97%.随访3年,中位生存时间为21.9个月,中位局部无进展生存时间为18.5个月,1、2、3年局部无进展生存率分别为66.7%、45.5%、30.3%,1、2、3年总生存率分别为69.7%、51.5%、30.3%.结论 三维适形放射治疗同期化疗综合治疗局限期小细胞肺癌疗效较好,毒副反应患者能耐受,安全可行.     

局限期食管小细胞癌根治性放化疗的疗效及预后影响因素分析

目的 分析局限期食管小细胞癌（SCEC）患者接受放化疗后的疗效及预后影响因素。方法 回顾性分析2000年1月至2016年12月江苏省中医院和浙江丽水市中心医院行放化疗治疗的38例局限期SCEC患者的临床资料,患者均行调强或三维适形放疗,放疗总剂量50~66 Gy,每日剂量1.8~2.0 Gy。放疗同步化疗（顺铂和依托泊苷）2周期以及序贯2周期。随访3年并分析患者中位生存时间、1年和3年生存率、治疗期间不良反应,利用Cox回归模型分析患者预后的影响因素。结果 38例患者平均随访时间（30.4±4.6）月,中位生存时间25.2个月（9~41个月）,1年和3年生存率分别为75.12%和32.31%。其中18例（47.37%）患者出现3~4级粒细胞减少,16例（42.11%）患者出现3~4级血小板减少,12例（31.58%）患者出现3级贫血。Cox回归模型结果显示,纵隔或胃周淋巴结转移为影响SCEC预后的危险因素。结论 根治性放化疗对局限期SCEC患者的疗效可期,有无纵隔或胃周淋巴结转移是其预后影响因素之一。     

世界首报三种染色体异常核型

本文报导了三种染色体异常核型，经湖南医科大学细胞遗传学国家中心鉴定均为世界首报异常核型．其异常核型分别为：46，x，inv（Y）（P11；q12），t（11；14）（q21；q24）、46，XY：t（11；14）（q23；q24）、46，XX，dup（3）（q21→q29）．     

Targeted therapy and promising novel agents for the treatment of advanced soft tissue sarcomas

Introduction: Soft tissue sarcomas (STS) are a rare and difficult to treat malignancy. Efforts to utilize targeted therapy have been ongoing for the last decade and have resulted in the approval of pazopanib for treatment of advanced disease. Although several other agents have been investigated, the inability to predict responses remains a limiting factor to the incorporation of these agents into treatment.

Areas covered: The authors summarize recent clinical findings from studies focused on targeted agents in STS. The authors also discuss the potential approaches and ongoing clinical trials with novel agents.

Expert opinion: A major challenge in the treatment of advanced STS remains a lack of predictive biomarkers to guide therapy and the heterogeneity of response among different histologies of sarcoma. Incorporation of predictive biomarker analysis into clinical trials is warranted. Additionally, mechanisms of treatment resistance and parallel pathways of tumor growth pose challenges in how we treat these tumors. An active area of research in STS is the use of novel combinations of agents, such as chemotherapy combined with multi-targeted agents. The potential of immune check point inhibitors is being explored in advanced STS and is hoped to further expand our treatment armamentarium.     

An open label, non-comparative phase II study of topotecan as salvage treatment for patients with soft tissue sarcoma

Background: The number of effective cytotoxic agents for the treatment of patients with metastatic soft tissue sarcoma (STS) is limited, especially when patients have failed anthracyline-based chemotherapy. Patients and methods: Between 1999 and 2000 a total of 16 patients with histologically proven STS progressing during or after first-line anthracycline-based chemotherapy were entered into this open-label, noncomparative study. Topotecan was administered as a 30-min infusion at a dosage of 1.5mg/m² on five consecutive days every 3 weeks. All patients had received an anthracycline- or ifosfamide-based first-line chemotherapy. Results: None of the 16 included patients achieved an objective response to topotecan. Six patients achieved stable disease (38%), lasting for at least 6 weeks in four patients (25%) and for less than 6 weeks in two patients (13%). Ten patients (62%) had progressive disease. The median time to progression was 79 days calculated from the start of topotecan therapy (range, 28–230). The treatment was well tolerated; however, both anemia and thrombopenia grade III/IV occurred in 25% of the patients as well as severe neutropenia in 69% of the patients. Nonhematologic toxicities grade III/IV such as diarrhea and severe bleeding occurred only in one patient each (6%). Discussion: Topotecan is well tolerated in anthracycline-resistant patients with metastatic STS, but no objective response has been observed in this trial.     

Assessing DSM-IV nicotine withdrawal symptoms: a comparison and evaluation of five different scales

Objective This study evaluated four of the major scales used to measure nicotine withdrawal symptoms plus one new scale. Methods Eighty-three smokers were randomly assigned to continue smoking (n=37) or abstain completely for 24 h (n=46), by which time the symptoms should become manifest. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) withdrawal symptoms (irritability, depression, restlessness, insomnia, anxiety, hunger and poor concentration) plus craving were measured at baseline and after 24 h. The scales tested were the Minnesota Nicotine Withdrawal Scale (MNWS), the Mood and Physical Symptoms Scale (MPSS), the Shiffman Scale (SS), the Wisconsin Smoking Withdrawal Scale (WSWS) and the newly developed Cigarette Withdrawal Scale (CWS). Results Measurement of withdrawal symptoms was robust in the case of all scales for total withdrawal score, irritability, restlessness, poor concentration and craving. The MNWS and CWS were less sensitive to depression; the WSWS and MNWS were less sensitive to insomnia; the MPSS was less sensitive to anxiety and hunger; the CWS and WSWS did not include restlessness as a distinct symptom; the SS did not include insomnia, and its scores tended to decline over time during ad lib smoking. Longer scales, using multiple items to measure each symptom, did not yield more reliable or accurate measurement than briefer scales. Conclusions To measure total withdrawal discomfort or craving, all of the scales examined can be recommended, and there is little to choose between them apart from length. When it comes to assessing individual symptoms, different scales have different strengths and weaknesses. There would be merits in developing a new questionnaire that combined the best features of the scales tested.     

同期放化疗治疗鼻咽癌肿瘤残留与预后的关系

目的探讨同期放化疗治疗鼻咽癌肿瘤残留与预后的关系。方法80例鼻咽癌患者随机分为两组:单纯常规放疗组(A组)42例。常规放疗+同期化疗(B组)38例。原发灶和阳性淋巴结区DT70～76Gy/35～38次,7～8周,预防区DT50～60Gy/25～30次,5～6周。化疗方案为顺铂(DDP)20mg/m2静脉滴注,d1～5,5-氟尿嘧啶(5-FU)750mg/m2静脉滴注,d1～5,每3周1个疗程,共2个疗程,并分析鼻咽部及颈部肿瘤残留情况。结果3年无瘤生存率(DFS)A组45.23%(19/42)、B组71.1%(27/38),二者差异有统计学意义(χ2=5.47,P<0.05);3年总生存率(OS)A组57.1%(24/42),B组73.6%(28/38),二者差异无统计学意义(χ2=2.38,P>0.05);鼻咽癌放射治疗后有残留者较无残留者的1、3、5年生存率低;颈部残留灶越大,生存率越低;有残留者的局部复发率增高。结论鼻咽癌放射治疗后有残留者的生存率下降,放射治疗后肿瘤残留可作为判断预后的一个指标。     

后程立体定向适形放射治疗加化疗治疗局限性晚期非小细胞肺癌临床探讨

目的　探讨后程立体定向适形放射治疗加化疗治疗局限性晚期非小细胞肺癌的疗效及患者的耐受性。方法　 4 8例患者于治疗前 4周行常规分割放射治疗 (2 Gy/ d,每周 5次 ) ,肿瘤吸收剂量 (DT) :4 0 Gy,后 2周针对肿瘤局部行立体定向适形放射治疗 ,DT:2 4～ 30 Gy(分割剂量 4～ 5 Gy,每周 3次 ) ,与此同时 ,于第 1周和第 5周采用异长春碱 +顺铂 (NP)方案共 2周期 ,异长春碱 (NVB) :2 5 mg/ m2 第 1天和第 8天静脉推注 ,顺铂(DDP) :30 mg第 1天～第 3天静脉滴注。结果　全部患者均能完成治疗计划 ,完全缓解 (CR)占 17% ,部分缓解(PR)占 75 % ,总有效率 (CR+PR)为 92 %。 1、2、3年局部控制率分别为 88%、5 0 %和 36 % ,1、2、3年生存率分别为 88%、4 7%和 2 9%。急性造血系统和胃肠道的毒性反应较重 ,但对症处理后均能耐受。结论　后程立体定向适形放射治疗加化疗治疗局限性晚期非小细胞肺癌有提高总生存率的趋势。     

One acute promyelocytic leukemia patient underwent complete molecular remission with consistent presence of t (2; 3) (p25; q21) karyotype

Objectives: This study aimed to explore why one acute promyelocytic leukemia (APL) patient underwent complete molecular remission in the persistent presence of the t (2; 3) (p25; q21) karotype.

Methods: One APL patient overexpressed PML/RARα (bcr1) and WT1 genes in the presence of the Fms-like tyrosine kinase-internal tandem duplication mutation, while cytogenetics showed t (2; 3) (p25; q21) and t (15; 17) (q22; q21). Cytogenetics and molecular biology were monitored throughout the treatment.

Results: After 5 weeks of induction chemotherapy, this case gained complete molecular biology remission with the presence of t (2; 3) (p25; q21). This status was still present during the follow-up consolidate and maintenance therapy.

Conclusion: For this patient, t (2; 3) (p25; q21) may be one kind of balanced translocation that leads to miscarriages or causes abnormalities in children, unrelated to leukemia or other malignancies.     

Adenovirus-mediated G(alpha)(q)-protein antisense transfer in neurons replicates G(alpha)(q) gene knockout strategies

Antisense approaches are increasingly used to dissect signaling pathways linking cell surface receptors to intracellular effectors. Here we used a recombinant adenovirus to deliver G-protein alpha(q) antisense into rat superior cervical ganglion (SCG) neurons and neuronal cell lines to dissect G(alpha)(q)-mediated signaling pathways in these cells. This approach was compared with other G(alpha)(q) gene knockdown strategies, namely, antisense plasmid and knockout mice. Infection with adenovirus expressing G(alpha)(q) antisense (G(alpha)(q)AS AdV) selectively decreased immunoreactivity for the G(alpha)(q) protein. Expression of other G(alpha) protein subunits, such as G(alpha)(oA/B,) was unaltered. Consistent with this, modulation of Ca(2+) currents by the G(alpha)(q)-coupled M(1) muscarinic receptor was severely impaired in neurons infected with G(alpha)(q)AS AdV whereas modulation via the G(alpha)(oA)-coupled M(4) muscarinic receptor was unchanged. In agreement, activation of phospholipase C and consequent mobilization of intracellular Ca(2+) by UTP receptors was lost in NG108-15 cells infected with G(alpha)(q)AS AdV but not in cells infected with the control GFP-expressing adenovirus. Results obtained with this recombinant AdV strategy qualitatively and quantitatively replicated results obtained using SCG neurons microinjected with G(alpha)(q) antisense plasmids or SCG neurons from G(alpha)(q) knockout mice. This combined antisense/recombinant adenoviral approach can therefore be useful for dissecting signal transduction mechanisms in SCG and other neurons.     

Treatment of advanced soft tissue sarcoma: efficacy and safety of trabectedin,a multitarget agent,and update on other systemic therapeutic options

Soft tissue sarcomas (STS) are rare mesenchymal cancers. Despite optimal management, nearly 50% of patients with localized disease will develop recurrence. The outcome for patients with metastatic STS is poor. There are few systemic treatment options available in this setting. Doxorubicin, with or without ifosfamide, is considered standard first line therapy. We herein review the evidence for the use of trabectedin in adult advanced soft tissue sarcoma. Some clinical trials have confirmed the activity of trabectedin as an effective and tolerable option for adult patients previously treated with doxorubicin and ifosfamide. Trabectedin was approved in the European Union and other countries based on the results of a randomized phase II trial involving patients with advanced liposarcoma and leiomyosarcoma receiving one of two different schedules of trabectedin. Recently a multicentre phase III trial randomized liposarcoma and leiomyosarcoma patients to receive either trabectedin or dacarbazine, demonstrating a significantly improved progression-free survival for patients treated with trabectedin compared to dacarbazine.     

多西他赛联合顺铂同步放化疗治疗局部晚期食管癌的疗效分析

目的研究多西他赛联合顺铂化疗同步三维适形放射治疗(3D-CRT)治疗局部晚期食管癌的近期疗效及毒副反应。方法将68名经病理确诊的食管癌局部晚期患者随机分为DP治疗组33例和PF治疗组35例。DP治疗组采用多西他赛联合顺铂,PF治疗组采用5-氟尿嘧啶联合顺铂,两组均采用3D-CRT计划,照射剂量为56～60Gy,2Gy/次,5次/周。结果 DP治疗组的总反应率为90.9%,PF治疗组的总反应率为82.9%;DP治疗组1、2年的总生存率分别为81.8%和48.5%;PF治疗组1、2年的总生存率分别为74.3%和37.1%;差异有统计学意义(P<0.05)。结论多西他赛联合顺铂化疗同步三维适形放射治疗治疗局部晚期食管癌近期疗效较好,但是还需要进行长期的随访观察。