奥沙利铂联合亚叶酸钙和5-氟尿嘧啶一线治疗晚期胃肠道肿瘤的研究

目的：评价奥沙利铂（OXA）联合亚叶酸钙（LV）和5-氟尿嘧啶（5-Fu）一线治疗晚期胃肠道肿瘤疗效与安全性。方法：OXA130mg／m^2，第1天；LV200mg，第1～5天；5-Fu450mg／m^2，第1～5天。每3周为1周期，至少2周期后评价疗效。结果：58例，均为术后转移或不能手术切除患者，其中CR2例（3．4％）。PR26例（44．8％），SD21例（36．2％），PD9例（15．5％），总有效率（CR＋PR）48．3％。有手术史者有效率54．5％，不能手术者有效率40．0％；胃癌有效率44．4％，大肠癌有效率51．6％。主要不良反应为恶心呕吐、轻度周围神经毒性及白细胞和血小板减少，无化疗相关死亡。结论：OXA联合LV和5-Fu一线治疗晚期胃肠道肿瘤有较好的疗效和耐受性。     

奥沙利铂联合甲酰四氢叶酸钙和氟尿嘧啶新辅助化疗方案治疗进展期胃癌的研究

目的评价奥沙利铂（OXA）联合甲酰四氢叶酸钙（LV）和氟尿嘧啶（5-FU）新辅助化疗方案（OXA-LV5FU2）治疗进展期胃癌的疗效与毒副作用。方法27例进展期胃癌患者接受OXA-LV5FU2治疗：OXA 100mg／m^2,静脉滴注2h,第1天;LV 200mg／m^2,静脉滴注2h后推注5-FU 400mg／m^2,后续5-FU 1g／m^2以麻醉镇痛泵持续48-72h恒速静脉输入,第1、2天。每2-3周为1个疗程,共3～4个疗程。观察新辅助化疗后肿瘤原发病灶的缓解情况及其不良反应。结果新辅助化疗后27例患者中24例获得手术切除,其中14例获得根治性切除。临床有效率为48．1％,其中3．7％（1例）完全缓解,44．4％（12例）部分缓解,33．3％（9例）病情稳定,18．5％（5例）病情进展。8例肿瘤TNM分期降低。不良反应主要为恶心呕吐、外周感觉神经异常、自细胞减少症、脱发、肝功能异常,对症治疗可缓解。无化疗相关死亡者。结论OXA-LV5FU2新辅助化疗方案在进展期胃癌的治疗中近期疗效显著,耐受性良好。     

奥沙利铂联合5—氟尿嘧啶—四氢叶酸治疗晚期大肠癌的临床观察

目的：评价沙利铂联合５－氯尿嘧嘧（５－Ｆｕ）－四氢叶酸（ＣＥ）治疗大癌的疗效及毒副反应。方法：收治大肠癌晚期患者３８例,按随机方法,分别入试验组２０例（奥沙利Ｆｕ－ＣＦ）和对照组１８例（５－Ｆｕ＋ＣＦ）。结果：试验组有效率为３０．０％,对照组５．６％,试验组疗效明显优于对照组（Ｐ〈０．０１）,且奥沙利铂对大肠癌常见转移部位和肝脏、腹腔淋巴结、盆腔及肺脏均可见临床疗效,毒副反应主要为神经感觉异常,其     

奥沙利铂联合低分子柑橘果胶对结肠癌细胞增殖与凋亡的影响

目的探讨奥沙利铂联合低分子柑橘果胶（LCP）对人结肠癌细胞的增殖及凋亡的影响。方法采用MTT法分别检测各浓度奥沙利铂单药和奥沙利铂联合低分子柑橘果胶对人结肠癌细胞（HT29）增殖的影响．计算两药物相互作用指数（CDI）。流式细胞仪检测IC50浓度奥沙利铂单药及联合用药处理HT29细胞的凋亡比例,采用Westernblot分析凋亡相关蛋白procaspase．3、8、9、PARP的变化。结果奥沙利铂单药与联合LCP用药对HT29细胞生长均有抑制作用,其效应呈时间和浓度依赖性：联合组对HT29细胞的生长抑制作用更为显著（P〈0．01）．两药物CDI小于1。单药与联合用药均能使HT29细胞凋亡比例增加,药物作用6、24、48h后单药组细胞凋亡率分别为（9．76±0．47）％、（20．45±0．74）％和（28．70±3．29）％,联合组细胞凋亡率为（20．63±0．69）％、（34．35±1．02）％和（49．47±3．04）％,联合用药组较单药组细胞凋亡更加显著（均P〈0．01）。单药组与联合组HT29细胞的凋亡相关蛋白procaspase-3、8、9、PARP蛋白的表达均下调,联合组较单药组procaspase-3、9、PARP蛋白表达下调更为显著．但两组细胞procaspase-8表达基本相同。结论LCP能增加奥沙利铂的细胞增殖抑制和诱导凋亡能力．该效应可能与活化线粒体凋亡途径有关。     

BH3-only在奥沙利铂诱导结肠癌细胞凋亡中的作用

目的研究BH3-only基因表达在奥沙利铂诱导人结肠癌细胞株凋亡中的作用及其机制。方法采用不同浓度（0．3、0．6、1．25、2,5、5、10和20mg／L）奥沙利铂处理人结肠癌细胞株SW480及HT29,应用MTT检测细胞生长抑制情况;流式细胞仪检测凋亡情况;荧光定量PCR检测BH3-only基Bim和PUMA表达。结果不同浓度奥沙利铂分别作用于结肠癌细胞SW480后,出现不同程度的细胞生长抑制作用,呈剂量依赖性。5mg／L和10mg／L浓度的奥沙利铂作用于SW480细胞24h后,细胞凋亡率分别为（4．87±0．55）％和（12．10±1．04）％,作用48h后分别为（11．47±0．85）％和（30．07±2．01）％,作用72h后分别为（28．99±2．12）％和（38．32±3．15）％,均显著高于相应时间点对照组细胞的凋亡率[（0．30±0．10）％、（0．40±0．10）％和（0．50±0．20）％,均P〈0．01]。同时Bim和PUMAmRNA表达水平也显著高于对照组（P〈0．05）。而同样处理的HT29细胞其生长抑制率、细胞凋亡率及Bim和PUMAmRNA表达水平与对照组比较差异无统计学意义（P〉0．05）。结论奥沙利铂具有抑制结肠癌细胞株SW480生长并诱导其凋亡的作用,其机制可能与促凋亡相关基因BH3-only（Bim和PUMA）表达增强有关。     

氟尿嘧啶加甲酰四氢叶酸术前化疗对人体胃癌细胞凋亡与增殖的影响

目的探讨氟尿嘧啶加甲酰四氢叶酸(5-FU加CF)术前化疗对人体胃癌细胞凋亡与增殖的影响。方法分别应用原位末端标记法(TUNEL)及免疫组织化学LSAB法,对35例胃癌患者经5-FU加CF术前化疗前后的肿瘤组织进行细胞凋亡指数(AI)及增殖细胞核抗原(PCNA)检测。结果5-FU加CF化疗后人体胃癌组织细胞AI为(6.245±2.127)%,明显高于化疗前(4.340±1.570)%(t=7.585,P<0.001)。PCNA表达化疗后为(42.21±8.01)%,明显低于化疗前(58.52±14.76)%(t=7.870,P<0.001)。结论在人体胃癌组织中,5-FU加CF术前化疗可诱导肿瘤细胞发生凋亡,并抑制其增殖。     

奥沙利铂化疗患者的护理干预

目的 探讨心理护理对减轻奥沙利铂化疗所致不良反应的效果。方法 将120例胃癌、结肠癌化疗患者随机分为干预组和对照组各60例，对照组采用常规化疗和护理，干预组在此基础上增加心理干预。3～6个疗程后比较两组化疗不良反应发生率。结果 干预组消化道反应、外周神经毒性反应发生率显著低于对照组（P〈0．05、P〈0．01）；两组白细胞和血小板减少率比较，差异无显著性意义（均P〉0．05）。结论 心理干预可减轻奥沙利铂所致的消化道不良反应和外周神经毒性反应。     

奥沙利铂联合5-FU术前动脉化疗对进展期胃癌的临床疗效

目的：探讨进展期胃癌患者术前用奥沙利铂（OXA）联合5-氟尿嘧啶（5-FU）行区域性动脉灌注化疗的临床效果。
方法：48例Ⅱ期以上胃癌患者,术前行区域性动脉灌注化疗（A组）,方案为OXA 130 mg/m+ 5-FU 750 mg/m,经股动脉插管行区域冲击化疗1次,8～12 d后接受手术。同期另48例相同临床分期的胃癌患者直接行手术治疗（B组）。两组术后均接受OXA /甲酰四氢叶酸钙/5- FU方案化疗6个周期,观察两组的毒副反应、手术并发症和临床疗效。
结果：A组有38例（79.2%）获得根治性切除;镜检32例（66.7%）出现组织病理学改变,如肿瘤组织坏死、淋巴细胞炎性浸润、癌细胞凋亡、以及间质水肿纤维组织增生等。B组有30例（62.5%）行根治性切除,根治切除率显著低于A组,两组间差异有统计学意义（P<0.05）,且B组病理检查未出现上述变化。A组术前化疗的毒性反应均限于Ⅰ～Ⅱ级;两组的术后并发症无统计学差异。A组患者的中位生存期为36.0个月;1,2,3年总生存率分别为79.2%,62.5%和52.1%。B组中位生存期为21.5个月;1,2,3年总生存率分别为66.7%,45.8%和35.4%。A,B组比较,2年和3年总生存率差异有统计学意义（P<0.05）。
结论：术前应用OXA/5-FU方案行区域性动脉灌注化疗可使肿瘤组织产生显著的组织病理学改变,有利于提高进展期胃癌根治性手术切除率及2,3年生存率。     

全反式维甲酸对人结肠癌细胞亚株SW480/M5增殖和凋亡的影响

目的 观察全反式维甲酸(ATRA)对人结肠癌细胞亚株SW480/M5增殖和凋亡的影响.方法 噻唑蓝(MTT)比色法检测1、2、4、8μmol/L ATRA作用24、48、72 h对SW480/M5细胞的抑制率.流式细胞仪检测8 μmol/L ATRA作用24、48、72 h及2、4μmol/L ATRA作用48 h的肿瘤细胞周期和凋亡率.结果 ATRA抑制SW480/M5细胞增殖作用呈一定时效和量效依赖性;8μmol/LATRA作用72 h明显抑制肿瘤细胞增殖,抑制率接近30％.2、4μmol/L ATRA作用SW480/M5细胞48 h或8μmol/L作用24 h,肿瘤细胞G1期比例开始降低,S期比例增加(P＜0.05).8umol/L ATRA作用48 h后,S期比例进一步增高,G2/M期细胞比例不增加;作用72 h后,G1期细胞比例进一步下降,伴G2/M期细胞比例增加(P＜0.05).8μmol/L ATRA作用24 h无明显诱导SW480/M5细胞凋亡作用,作用48 h或72 h可诱导肿瘤细胞凋亡,但凋亡率差异无统计学意义(P＞0.05).结论 8μmoL/LATRA作用48 h或72 h通过阻滞SW480/M5细胞在S期或(和G2/M)期,并诱导肿瘤细胞凋亡,可明显抑制肿瘤细胞增殖.     

Advances in the adjuvant treatment of colorectal cancer

BACKGROUND: There have been numerous advances in the adjuvant therapy of colon cancer in the last two decades. METHODS: This review outlines the historical perspectives of adjuvant treatment as well as current and emerging standards of care. RESULTS: Although previous regimens included a variety of equivalent schedules of 5-fluorouracil and folinic acid, integration of newer drugs such as oxaliplatin are offering significant improvements in disease-free survival. The use of targeted agents such as bevacuzimab creates the potential to further increase cure rates in the adjuvant setting. The current low rate of referral of eligible patients for chemotherapy in Australia is also discussed. CONCLUSION: Adjuvant therapy for colon cancer is making major strides as we attempt to cure more patients.     

Audit of definitive colorectal surgery in patients with early and advanced colorectal cancer

Background : The role of surgery in patients with advanced colorectal cancer may be questioned in the era of specialized intensive palliative care. Should patients with advanced disease be advised against surgery because of the risks of the surgery itself? In this study, the perioperative outcomes in patients undergoing definitive surgery for early (Dukes’ stages A, B and C) and advanced colorectal cancer (stage D) were examined. Methods : All patients undergoing definitive surgery for colorectal cancer during a 15‐year period were identified. Details of tumour site and stage, surgery performed, perioperative complications and postoperative mortality were compared. Results : A total of 374 patients underwent definitive surgery. There were 193 men, a male : female ratio of 1:0.9. Seventy‐one patients had advanced disease. There were no differences between the early and advanced groups in perioperative requirements for either blood or total parenteral nutrition. In the advanced group, more operations were performed as emergencies than in the early group (32.4 vs 17.5%; P < 0.01) and more patients presented with bowel obstruction in the advanced group (23.9 vs 10.2%; P < 0.01). There were no site differences between the early and advanced groups and no differences between the operations performed except that endo‐anal destruction was not performed in advanced patients. There were no differences in perioperative morbidity or mortality in the groups studied. Conclusion : Resection rates, operation type and postoperative morbidity and mortality were similar in patients with both early and advanced colorectal cancers. In terms of perioperative outcome, the presence of advanced cancer, per se, should not, therefore, be a justification to decline surgery.     

The prognostic value of flow cytometric DNA analysis in colorectal cancer patients

An association between DNA aneuploidy of tumor cells and a poorer clinical outcome of patients has been recognized in various human solid tumors. In this article, the prognostic value of flow cytometric DNA analysis in colorectal cancer patients is briefly overviewed. DNA aneuploidy appeared to correlate with more advanced disease and a poorer survival in colorectal cancer patients, but reported results were not always consistent. DNA ploidy as a marker for predicting the survival of colorectal cancer patients should not therefore be viewed in isolation, but should be evaluated in combination with other conventional prognostic variables. The S-phase cell compartment within a tumor appears to be promising as a marker for predicting the survival of colorectal cancer patients, but there remain technical problems in establishing an accurate estimation of the S-phase cell compartment within a tumor by conventional flow cytometry. The application of a bromodeoxyuridine (BrdU)-specific monoclonal antibody might be an useful tool for obtaining the accurate flow cytometric estimation of the S-phase cell population within a tumor.     

The antioxidant n-acetylcysteine increases 5-fluorouracil activity against colorectal cancer xenografts in nude mice

The antioxidant pyrrolidinedithiocarbamate improves the therapeutic efficacy of 5-fluorouracil (S-FU) against HCT-15 colorectal cancer cell line xenografts in nude mice without increasing toxicity to normal intestinal or hematopoietic tissues. In the current study we have shown that a similar clinically licensed antioxidant, N-acetylcysteine (200 mg/kg), can modulate the activity of S-FU (120 mg/kg) against HCT-15 tumor xenografts in nude mice. We demonstrate that this effect is accompanied by a sustained elevation in p53-independent apoptosis without accompanying alterations in cell cycle kinetics. Extensive tumor necrosis is also a prominent feature of treatment; however, no significant impairment of neovascularization as assessed by intratnmor microvessel density occurred. We believe that the clinical efficacy of N-acetylcysteine as an adjunct to 5-FU in advanced colorectal cancer should be investigated further. Supported by the Christie Hospital Endowment Fund (Mr. Bach) and by grant SP2460/0101 from the Cancer Research Campaign (Profs. Potten and Watson). Presented at the Forty-First Annual Meeting of The Society for Surgery of the Alimentary Tract, San Diego, Calif., May 21–24, 2000, and the Ross/SSAT Residents and Fellows Research Conference, Ranch0 Bernardo, San Diego, Calif., May 20, 2000.     

A prospective audit of early stoma complications in colorectal cancer treatment throughout the Greater Manchester and Cheshire colorectal cancer network

Aim The study aimed to identify the incidence of early stoma problems after surgery for colorectal cancer to identify predisposing factors and to assess the effect on discharge from hospital and the greater need for community stoma care. Method A prospective study of 192 patients was carried out over a six‐month period in the 13 units of the Greater Manchester and Cheshire Cancer Network. Stoma problems were categorized into fistula, leakage, pancaking, necrosis, retraction, separation, stenosis, skin problems, parastomal hernia, suboptimal stoma site and need for resiting or refashioning. Differences in incidence between units (anonymized) were analysed, and the effect of stoma complications on length of hospital stay and the need for additional community stoma care was determined. Results One hundred and ninety‐two patients with stomas were included, of which 52 (27.1%) were identified as being problematic (range 0–66.7% between units). Significant risk factors included stoma type (colostomy) (P < 0.05), short stoma length (P = 0.006), higher BMI (P = 0.043), emergency surgery (P = 0.002) and lack of preoperative site marking (P < 0.001). Problematic stomas were associated with longer hospital stay (P < 0.001) and increased community care (P < 0.001). Conclusion Stoma type, stoma length, body mass index, emergency surgery and lack of preoperative marking were significant risk factors. Overall complication rates compare favourably with other studies.     

亚叶酸与5－FU联合化疗防治结直肠癌复发（附87例分析）

自１９８８年以来采用亚叶酸和５－ＦＵ联合化疗结直肠癌２６２例，经随访生存逾５年者８７例。６６例为术后辅助化疗组，属ＤｕｋｅｓＡ期１４例，Ｂ期１５例，Ｃ期３７例。２１例为治疗组，均系Ｄ期病例。化疗采用亚叶酸１５０～３００ｍｇ／ｄ和５－ＦＵ１０００ｍｇ／ｄ静脉滴注，连续５天为１疗程，每月１次，共６～９疗程。结果显示，辅助化疗组总的５年生存率为６６．６７％。治疗组总有效率５２．３８％。本研究表明，亚叶酸和５－ＦＵ联合化疗不论作为辅助或治疗均是安全和有效的选择。     

结肠癌患者奥沙利铂治疗体验的质性研究

对15例用奥沙利铂治疗的结肠癌患者进行半结构式访谈,归纳其症状体验主要为疲乏,食欲不振和味觉改变,恶心、呕吐及腹泻,四肢麻木和疼痛;情感体验主要是恐惧,抵触和无奈,矛盾,压抑和担忧。护理人员应采取有效措施减轻化疗痛苦,提高患者生命质量。