肝切除治疗原发性肝癌自发性破裂

目的 探讨肝切除治疗原发性肝癌自发性破裂(简称肝癌破裂)的作用。方法 分析我院1973年以来采用肝切除术治疗肝癌破裂12例的临床资料。结果 本组男10例，女2例。平均年龄42(22—65)岁。11例为急症肝切除术，1例为2期肝切除，包括肝左外叶切除6例，左内叶切除1例，左半肝切除1例，右肝部分切除2例，肿瘤局部切除2例。本组中Child-Paugh肝功能分级A组的11例中无死亡；B组者1例术后死于肝衰，手术死亡率为8．3％。术后生存的1例均获随访，平均生存时间为16．5个月，1，3，5年生存率分别为72．7，18．2％，9．1％。其中1例已无瘤生存25年9个月。结论 肝切除是治疗肝癌破裂的最好方法，当有可能时应争取施行。肝切除治疗肝癌破裂可能使患者获行长时间生存。     

胆囊腺瘤-腺癌中的DNA含量和基因表达

目的 研究胆囊腺瘤从增殖到恶变中腺上皮细胞的增殖变化和基因表达。方法PCR-RFLP法测定APC、ras基因突变,ABC免疫化学组织染色法测定p53蛋白表达。用TJTY-300全自动图像分析仪测定胆囊上皮细胞核异型性和DNA含量。结果 上皮细胞核异型性和DNA含量在胆囊腺瘤-腺癌过程中逐渐增加。胆囊腺瘤中异倍体比例与腺瘤的大小有明显的关系,直径≥1cm异倍体显著增加(P<0.05)。在胆囊腺瘤-腺癌过程中可检测到APC基因和RAS基因突变。P53蛋白在这一过程中不表达。结论 胆囊腺瘤-腺癌的过程是胆囊癌发生中一条重要的途径。当胆囊腺瘤直径≥1cm时具有明显的癌变潜能。其分子改变机制与胆囊上皮不典型增生-原位癌途径不同。     

肝癌门静脉癌栓多排螺旋CT三维成像

目的 探讨门静脉癌栓多排螺旋CT3D成像的临床意义。方法 收集了57例门静脉3D成像,6例正常,5例肝硬化门脉高压,42例肝癌门静脉癌栓,4例肝门部淋巴结肿大患者,所有病例来源于肝脏常规双期扫描。对比剂按1.5-2ml/kg,对比剂注射流率2.5-3ml/s,门脉期延迟时间60-70s。对肝癌形成的42例门静脉癌栓进行轴位和3D成像观察,并行两组对照。结果 根据癌栓不同部位分为门脉左支(13例)、右支(20例)、主干(9例)3种类型。3D成像与轴位之间对显示门静脉癌栓没有差异性(P>0.05),但3D对显示主干栓塞形成的侧支循环优于轴位。结论 门静脉癌栓多排螺旋CT3D成像可较好地多方位显示癌栓部位及癌栓类型,CT3D成像和轴位结合可更好地对门静脉癌栓作出判断,以进一步指导临床对治疗方案的选择。     

Survivin反义RNA真核表达载体的构建及鉴定

目的 为了特异封闭白血病细胞survivin的表达，抑制其功能，本实验构建了survivin反义核酸载体并导入白血病细胞系中。方法 应用RT—PCR获得survivin的cDNA片段，反向插入pcDNA3质粒载体中；经限制性酶切和测序鉴定所构建的反义核酸是否正确；采用电转染方法将重组体导入HL—60细胞中；RT—PCR技术检测转染细胞survivin表达的变化。结果 经限制性酶切和测序鉴定证明survivin反义核酸已成功构建；RT—PCR产物电泳结果显示，与转染前细胞、空质粒转染细胞相比，转染survivin反义核酸的细胞survivin mRNA水平明显降低。结论 本实验已成功建立了survivin反义核酸真核表达载体，而且在白血病细胞系中发挥了特异封闭作用，为进一步研究survivin反义核酸在白血病治疗中的作用提供了实验基础。     

Phase I pharmacological and bioavailability study of oral diflomotecan (BN80915), a novel E-ring-modified camptothecin analogue in adults with solid tumors.

PURPOSE: Diflomotecan (BN80915) is an E-ring modified camptothecin analogue that possesses greater lactone stability in plasma compared with other topoisomerase I inhibitors, a potential advantage for antitumor activity. As with other camptothecins, oral administration has pharmacological and clinical advantages. This Phase I study was performed to assess the feasibility of the administration of oral diflomotecan, to determine the maximum-tolerated, dose its bioavailability, and to explore the pharmacokinetics. EXPERIMENTAL DESIGN: An initial i.v. bolus was administered to assess the bioavailability of diflomotecan. Fourteen days later, diflomotecan was administered p.o. once daily for 5 days to adult patients with solid malignant tumors and repeated every 3 weeks. BN80915 and its open lactone form BN80942 were measured. RESULTS: Twenty-two patients entered the study and received a total of 57 cycles of oral diflomotecan at flat dose levels of 0.10, 0.20, 0.27, and 0.35 mg. The main toxicity was hematological, but some patients experienced alopecia, mild gastrointestinal toxicity, and fatigue. At the 0.35-mg dose level, 2 of 4 patients experienced dose-limiting toxicity comprising grade 3 thrombocytopenia with epistaxis and febrile neutropenia in 1 patient and uncomplicated grade 4 neutropenia lasting for >7 days in another. Toxicity was acceptable at the 0.27-mg dose level at which dose-limiting toxicities were observed in 3 of 12 patients (grade 4 neutropenia > 7 days, complicated by fever in 1 patient but without other signs of infection). After two cycles of diflomotecan, 6 patients had disease stabilization, which was maintained in 2 patients for 9 months and >1 year, respectively. Diflomotecan pharmacokinetics were linear over the dose range studied. Systemic exposure correlated with the fall in WBC counts. The mean oral bioavailability (+/-SD) was 72.24 +/- 59.2% across all dose levels. Urinary excretion of BN80915 was very low. CONCLUSIONS: The recommended oral diflomotecan dose for Phase II studies is 0.27 mg/day x 5 every 3 weeks. This regimen is convenient and generally well tolerated with a favorable pharmacokinetic profile and high but variable bioavailability.     

Psychosocial Support for Women with Advanced Breast Cancer

Women with advanced breast cancer frequently experience psychologic distress as a result of their illness and its treatment. This distress may be manifest as depression, anxiety, symptoms of the stress-response syndrome, difficulty coping and social isolation. Six randomized trials of psychosocial interventions have been conducted in metastatic breast cancer. Five of these evaluated group psychosocial support – supportive-expressive therapy in three studies, cognitive-behavioral in one, and a combination of cognitive-behavioral and supportive therapy in another. All of these studies identified psychological benefits, notably improvement in mood, pain control and coping, although benefits were small in one study that provided the control group with a home cognitive-behavioral study program. One study identified an unexpected survival benefit associated with a group intervention – three subsequent studies have failed to replicate this result. Survival results of one additional ongoing study are pending.Studies in early breast cancer, and in patients with a spectrum of other cancers, have demonstrated benefits of individual psychological interventions, educational interventions and relaxation/self-hypnosis/imagery interventions, however, these have not been adequately evaluated in metastatic breast cancer.Based on these results, it is recommended that psychosocial support be offered to women with advanced breast cancer. Current research does not provide sufficient information to determine the optimal type of intervention to be used, or the optimal timing and duration of such interventions. Furthermore, it is not clear which patients benefit the most from psychosocial intervention and whether there are some patients who do not require psychosocial intervention. Research to address these issues is recommended.