肝癌切除术中局部植入5-氟尿嘧啶缓释剂的安全性研究

目的探讨肝癌术中局部使用5-氟尿嘧啶缓释剂化疗的安全性。方法经根治性手术切除的肝癌患者随机分为两组,治疗组腹腔内植入5．氟尿嘧啶缓释剂,对照组术中不进行腹腔内干预性治疗。观察5-氟尿嘧啶缓释剂植入后对血常规、肝肾及凝血功能、腹腔引流量、术后并发症和住院日等的影响。结果两组患者术后血常规、肝。肾及凝血功能等指标比较,差异均无统计学意义（P〉0．05）。植入组术后局部疼痛、胸腔积液发生率及腹腔引流液量均明显高于对照组（P〈0．05）,其它术后并发症发生率及住院日两组间差异均无统计学意义（P〉0．05）。结论肝癌术中使用5-氟尿嘧啶缓释剂局部区域化疗,对机体器官功能影响较小,术后并发症较轻,具有较好的安全性。     

食管癌术中植入5-氟尿嘧啶缓释剂的安全性

[目的]探讨术中植入5-氟尿嘧啶缓释剂对食管癌患者的安全性。[方法]82例食管癌患者行手术治疗并在术中植入缓释性5-氟尿嘧啶；同时设对照组82例，予单纯手术。检测两组患者术前术后肝肾功能、白细胞、免疫指标，比较术后并发症的发生情况。[结果]术后两组患者肝肾功能及白细胞数值无显著性差异（P＞0.05；术后实验组CD3^＋水平低于对照组（P＜0.05，其余各项免疫指标无显著性差异（P＞0.05。实验组术后切口感染发生率为4.88%（4/82），对照组为1.25%（1/80），P＜0.05，其余术后并发症发生率无显著性差异（P＞0.05。[结论]术中植入5-氟尿嘧啶缓释剂治疗食管癌是比较安全的。     

进展期胃癌术中植入5-氟尿嘧啶缓释剂的临床观察

目的探讨术中腹腔内植入5-氟尿嘧啶缓释剂对进展期胃癌患者的术后疗效及并发症发生率的影响。方法2008年6月至2010年6月共收治61例进展期胃癌患者。治疗组30例行标准根治术,术中腹腔内植人5一氟尿嘧啶缓释颗粒,对照组31例予以单纯手术,术前术后检测两组患者的白细胞计数,观察两组术后并发症的发生情况并进行随访。结果治疗组较对照组术后腹腔引流量多（P〈0．05）,白细胞计数虽低于对照组（P〈0．05）,但仍在正常范围。两组切口感染率、吻合口瘘发生率、腹膜炎发生率、肠粘连梗阻率差别均无统计学意义（P〉0．05）。随访2年,治疗组局部复发率6．7％,2年生存率83．3％,明显好于对照组的17．2％和75．9％（P〈0．05）。结论术中腹腔内植入5．氟尿嘧啶缓释剂近期疗效较好,且安全可靠。     

老年进展期胃癌术中早期腹腔化疗安全性和耐受性观察

目的观察老年进展期胃癌患者术中植入氟尿嘧啶缓释剂对并发症发生率、肠功能恢复时间、肝肾功能、白细胞计数及细胞免疫功能的影响。方法治疗组37例老年进展期胃癌患者行标准根治性手术,术中腹腔内植入氟尿嘧啶缓释剂;同期设对照组30例,予单纯根治手术。术前及术后检测两组患者的肝肾功能、白细胞计数及细胞免疫功能指标,比较术后并发症发生率及肠功能恢复时间。结果两组患者术后的并发症发生率、肠功能恢复时间、肝肾功能及白细胞计数指标差异无统计学意义（P〉0．05）。治疗组CD3＋水平低于对照组（P〈0．05）。结论老年胃癌患者术中植入氟尿嘧啶缓释剂近期临床观察具有良好的安全性和耐受性,对肝肾功能影响较小,不增加术后并发症,但对细胞免疫功能有一定的抑制作用。     

中晚期胃癌术中腹腔内植入氟尿嘧啶缓释剂37例

[目的]评价中晚期胃癌术中腹腔内植入氟尿嘧啶缓释剂的疗效。[方法]112例Ⅲb期胃癌分三组：治疗组1为37例，术中即时低渗温热腹腔化疗联合腹腔内植入氟尿嘧啶缓释剂，治疗组2为38例，术中即时低渗温热腹腔化疗联合术后早期腹腔化疗，对照组为37例。[结果]三组病例腹腔化疗的并发症比较均无显著性差异，治疗组1消化道反应的发生率（2．70％）低于治疗组2（21．05％，P〈0．05）。三组病例1年生存率无显著性差异，治疗组1的2年生存率（70．27％）明显高于对照组（40．54％，P〈0．05），但与治疗组2（55．26％）比较无显著性差异。[结论]中晚期胃癌术中腹腔内植入氟尿嘧啶缓释剂是一种有效且毒副反应轻的腹腔化疗方法。     

食管癌根治术中植入5-氟尿嘧啶缓释粒子行间质化疗的疗效观察

目的探讨食管癌根治术中植入5-氟尿嘧啶缓释粒子行局部化疗的临床疗效和安全性。方法将107例确诊食管癌患者随机分为单纯食管癌根治术组（对照组,n=53）和食管癌根治术中植入5-氟尿嘧啶缓释粒子组（植入组,n=54）,比较两组患者手术前后实验室指标、术后并发症和3年生存率等情况。结果对照组与植入组在治疗前后实验室指标、组间并发症发生率、组间术后1年生存率比较,差异无统计学意义均（P〉0．05）;植入组术后3年生存率（61．11％）优于对照组（39．62％）（P〈0．05）：植入组术后3年局部复发率（18．52％）低于对照组（45．28％）（P〈0．05）。结论食管癌根治术中植入5－氟尿嘧啶缓释粒子能够将药物直接植入病灶部位以维持缓慢释放高浓度状态,提高药物敏感期肿瘤细胞的杀伤力,从而改善患者的临床症状和提高远期生存率,值得临床继续研究和探讨。     

卵巢癌术中腹腔内播撒缓释氟尿嘧啶的临床研究

目的评价卵巢癌患者术中腹腔内播撒氟尿嘧啶缓释剂后的疗效和安全性。方法 60例卵巢癌患者随机分为治疗组（术中播撒氟尿嘧啶缓释剂）和对照组（常规手术）各30例。比较2组患者治疗后1周内局部并发症和引流量情况,同时密切观察全身毒副反应。结果治疗组术后3~7 d腹腔引流量较对照组明显减少（P〈0.05）;并发症未见增多（P〉0.05）。同时2组患者全身毒副反应均能耐受,手术切口愈合良好。结论术中播撒氟尿嘧啶缓释剂简便、安全、有效,值得临床推广。     

缓释氟尿嘧啶在胃肠恶性肿瘤术中的应用

[目的]探讨区域性缓释化疗在消化道恶性肿瘤中的疗效。[方法]68例胃肠肿瘤患者随机分为两组：治疗组38例,术中使用植入缓释氟尿嘧啶;对照组30例,术中未使用缓释氟尿嘧啶。两组临床病理资料具有可比性。[结果]使用植入缓释氟尿嘧啶治疗组未出现明显的胃肠道反应。治疗组吻合口瘘1例、肠梗阻1例、腹腔化脓性感染1例;而对照组吻合口瘘1例、肠梗阻1例、无腹腔化脓性感染。两组并发症发生率比较无统计学差异（7．9％vs6．7％,χ^2=0．037,19=0．847）。治疗组2年局部复发率为5．3％,而对照组2年局部复发率为23.3％（χ^2=0．060,P=0．027）;两组2年无远处转移率无统计学差异（χ^2=0．060,P=0．807）。治疗组与对照组术后2年生存率分别为94．7％和76．7％（P〈0．05）。[结论]术中植入缓释氟尿嘧啶安全、可行,可降低胃肠肿瘤术后复发率及提高术后生存率．具有一定的临床应用价值。     

氟尿嘧啶缓释植入剂与组织间插植在宫颈癌中的疗效观察

目的探讨氟尿嘧啶缓释植入剂与组织间插植在巨块型年轻宫颈癌中的疗效、不良反应及对卵巢功能的影响。方法选取2009年4月－2010年1月收治的ⅠB2期～ⅡA期宫颈鳞状细胞癌患者20例,其中10例予氟尿嘧啶缓释剂局部植入,10例予组织间插植,观察2组局部肿瘤的消退情况,监测患者治疗后的不良反应和卵巢功能变化。结果治疗3周后,氟尿嘧啶缓释剂植入组和组织间插植组治疗有效率分别为70％、80％,两组比较差异无统计学意义（P>0.05）;组织间插植组治疗后FSH、LH升高、E2下降,出现卵巢功能减退（P<0.05）;两组手术时间、术中出血量、术中并发症及术后早期并发症相比较,差异无统计学意义（P>0.05）。结论氟尿嘧啶缓释植入剂在治疗巨块型宫颈癌中具有有效的抗肿瘤作用、不影响卵巢功能。     

肾癌根治术后生物化疗的临床观察

目的：探讨生物化疗在肾癌根治术后的治疗作用。方法：对69例行肾癌根治术后的患者按治疗方法分为A、B两组，A组术后用α-干扰素和5-氟尿嘧啶，B组用白细胞介素-2、α-干扰素和5-氟尿嘧啶联合治疗。比较两组术后生存率。结果：通过随访比较，两组早期（Ⅰ—Ⅱ期）肾癌根治术后患者1年-3年生存率差异无显著性（P〉0．05），晚期（Ⅲ期）肾癌根治术后患者3年生存率差异有显著性（P〈0．05）。所有患者没有发生严重毒副反应。结论：白细胞介素-2、α-干扰素联合5-氟尿嘧啶对晚期肾癌有效，疗效优于仅用α-干扰素和5-氟尿嘧啶。     

胸外科肿瘤患者手术中植入5-Fu缓释剂初步疗效观察

目的初步观察对胸外科肿瘤患者手术中植入氟尿嘧啶缓释剂的安全性。方法我科于2008年1月8日开始至2008年6月10日共治疗胸外科肿瘤患者80例,随机分为治疗组（手术中植入5-Fu缓释剂）和对照组（即常规手术）各40例。两组用药前后对照常规检查,心、肺、肝、肾功能,血、尿常规,肝、肾功能等指标。观察手术后引流量及并发症的发生情况。结果两组用药前后对照常规检查,治疗组手术后引流量较多,并发症未见增多,伤口愈合良好,未见延迟和不愈合。近期生活质量未见降低。结论手术中植入5-Fu缓释剂（即中人氟安）简便、易行、副作用少。     

Increasing tumoral 5-fluorouracil concentrations during a 5-day continuous infusion: a microdialysis study

Purpose

Response to anticancer therapy is believed to be directly related to the concentration of the anticancer drug in the tumor itself. Assessment of intra-tumor drug pharmacokinetics can be helpful to gain more insight into mechanisms involved in the (in)sensitivity of tumors to anticancer therapy. We explored the pharmacokinetics of 5-fluorouracil in both plasma and tumor tissue during a 5-day continuous infusion of 5-fluorouracil in patients with cancer. Sampling for measurement of 5-fluorouracil in tumor tissue was performed using microdialysis.

Experimental design

In seven patients with an accessible (sub)cutaneous tumor treated with a continuous 5-fluorouracil infusion, plasma and microdialysate samples from tumor and normal adipose tissue were collected over a period of 5?days.

Results

For six patients, drug concentrations in both tumor tissue and plasma were available. Concentration?Ctime curves of unbound 5-fluorouracil were lower in tumor tissue compared to the curves in plasma, but exposure ratios of tumor tissue versus plasma increased during the 5-day infusion period. The presence of circadian rhythmicity of 5-fluorouracil pharmacokinetics in the tumor itself was demonstrated as 5-fluorouracil concentrations in tumor extracellular fluid were higher during the night than during daytime.

Conclusion

Microdialysis was successfully employed in patients with cancer during a continuous 5-day 5-fluorouracil infusion. Plasma and tumor pharmacokinetics of 5-fluorouracil differed substantially with increasing 5-fluorouracil concentrations in tumor over time, possibly resulting from a lowered interstitial fluid pressure by 5-fluorouracil itself. This microdialysis 5-fluorouracil model might be useful to monitor the effect of drug delivery modulating strategies in future studies.     

进展期胃癌术中应用氟尿嘧啶缓释植入剂腹腔化疗的临床疗效

目的:探讨进展期胃癌术中应用氟尿嘧啶缓释植入剂腹腔化疗临床疗效及影响胃癌预后因素.方法:选取2010年1月至2010年12月于哈尔滨医科大学附属肿瘤医院胃肠外科行R0根治术进展期胃癌患者255例.分为3组,即A组(对照组,仅行手术治疗)、B组(腹腔化疗组,氟尿嘧啶缓释植入剂3支)、C组(腹腔化疗组,氟尿嘧啶缓释植入剂6支),观察并分析3组临床治疗效果.结果:应用氟尿嘧啶缓释植入剂腹腔化疗可延长进展期胃癌患者术后总生存时间,术后3年、5年生存率高于对照组,其中应用6支氟尿嘧啶缓释植入剂术后5年生存率要高于应用3支氟尿嘧啶缓释植入剂;三组在术后总生存时间和术后1年、3年生存率比较,差异均不具有统计学意义(P＞0.05);5年生存率,差异具有统计学意义(P＜0.05).影响胃癌预后的独立因素包括肿瘤细胞分化程度、病理N分期、病理TNM分期、清扫淋巴结总数和清扫淋巴结阳性数.结论:进展期胃癌术中应用氟尿嘧啶缓释植入剂腹腔化疗可在一定程度上提高胃癌患者术后生存率,值得在临床中应用.     

Pharmacokinetic study and effectiveness evaluation of slow-release PLGA-5-fluorouracil microsphere

Purpose

The aim was to develop a slow-release poly-lactic-co-glycolic acid (PLGA)-5-fluorouracil microsphere, study the pharmacokinetic characteristics as well as to evaluate the effectiveness and safety of this preparation on colorectal tumor in vivo.

Methods

The PLGA-5-fluorouracil microsphere was prepared based on a spray-drying method, and the drug loading of 5-fluorouracil (the percentage of 5-fluorouracil content in the whole microsphere), in vitro 5-fluorouracil release profile and pharmacokinetic characteristics were carried out through high-performance liquid chromatography. The inhibiting effect on tumor growth and safety was examined using in vivo subcutaneously (s.c.) inoculated colorectal tumor models of nude mice.

Results

The size of the microsphere was less than 100 μm, drug loading was 20 % and drug release time lasted as long as 30 days. Slow-release PLGA-5-fluorouracil microsphere had longer half-life time (t _1/2), larger apparent volume of distribution (V _d ) and smaller area under the curve (AUC) compared with 5-fluorouracil. PLGA-5-fluorouracil microsphere significantly restrained tumor growth and this effect correlated with decreased expression of vascular endothelial growth factor in tumor cells. Body weight measurement and blood analysis did not suggest significant adverse effects on the mice during the study.

Conclusions

The slow-release PLGA-5-fluorouracil microsphere developed here was suitable for regional use; it has pharmacokinetic advantages and appears safe and effective in controlling the tumor growth. This preparation shows promise in reducing local recurrence of colorectal cancer after resection, but needs further investigation.     

TCF方案与PF方案治疗晚期食管癌的临床研究

目的:观察比较紫杉醇联合顺铂、氟尿嘧啶(TCF方案)与顺铂加氟尿嘧啶(PF方案)两个方案治疗晚期食管癌的临床疗效和毒性反应。方法:共69例患者,分别用TCF、PF方案化疗,28天为1个周期。2个周期以后按照WHO标准进行疗效评价。结果:TCF方案可评价疗效者32例,CR2例,PR15例,有效率53.1%。中位疾病进展时间为5.4个月,中位生存时间10.1个月。可评价毒副反应33例。主要不良反应为脱发、中性粒细胞降低,恶心、呕吐也较常见。PF方案可评价疗效者29例,PR14例,有效率48.3%。中位疾病进展时间3.9个月,中位生存期8.7个月。主要不良反应为恶心、呕吐。结论:TCF方案对晚期食管癌疗效好,毒副反应可耐受,可以考虑作为治疗晚期食管癌的主要治疗方案。     

UFT concentration in various tissues from cancer patients

UFT, an antitumor drug combined of Tegafur 1 and Uracil 4, was administered preoperatively to 23 cancer patients including 11 cases of breast, 8 of gastric, 2 of colon and 2 of other cancers. Tissue specimens of different sites and serum samples were collected during the operation: cancer tissues, normal breast, normal gastric, colon or rectal wall, lymph nodes and subcutaneous fatty tissues, etc., and concentrations of tegafur (FT), 5-fluorouracil (5-FU) and uracil were studied using HCLP or GC-MF methods. In most cases, 5-FU and uracil concentrations detected in cancer tissues from the patients were higher than those found in non cancer sites. FT and 5-FU fractions in cancer tissues were found to be higher than those of the patients receiving only 800 mg of Tegafur fine granules as previously reported. Patients with benign tumor having mastopathy or were reported to show very low 5-FU concentration in tissue which was almost undetectable. From the above results, it has been suggested that UFT is a useful drug in cancer chemotherapy.     

经动脉灌注吉西他滨和5-氟尿嘧啶联合热疗治疗中晚期胰腺癌的临床分析

目的：探讨经动脉灌注吉西他滨（Gemcitabine,商品名健择）和5-氟尿嘧啶（5-FU）联合内生场热疗治疗中晚期胰腺癌的临床疗效。方法：18例中晚期胰腺癌患者,采用改良Seldinger技术,动脉插管后选择性置管于胰腺癌的供血动脉,灌注吉西他滨1000mg／m^2;之后行内生场热疗,热疗同时经动脉留置导管灌注卡铂400mg／m^2;热疗后,用输液泵经动脉留置管灌注5-FU 1g,连用2d。随访观察客观疗效、临床受益反应、患者的生存期及不良反应等。结果：18例患者的客观缓解率为22．20％,临床受益反应为44．40％,Kaplan-Meier法计算6、9和12个月的累积生存率分别为83．33％、66．67％和33．33％,频数分布法计算中位生存期为11个月。结论：经动脉灌注吉西他滨和5-FU联合内生场热疗治疗中晚期胰腺癌可获得较好的临床疗效,患者耐受良好,值得进一步研究。     

Intermittent low-dose cisplatin infusion as a possible modulator of 5-fluorouracil

Background This study was designed to determine whether 5-fluorouracil combined with intermittent low-dose cisplatin (cis-diaminedichloroplatinum, CDDP), a 5-fluorouracil modulator, would be an effective antitumor regimen. Methods Sarcoma 180 tumor (mouse sarcoma) was implanted in mice, and intravenous CDDP injections (0.5 mg/kg) were given at intervals of 12 hours. Tumors were removed on days 1, 3, and 5 of treatment for quantification of the tumor tetrahydrofolate and blood platinum levels. One group of mice was treated with a combination of CDDP and 5-fluorouracil (10 mg/kg), and another group was treated with 5-fluorouracil alone. Tumor thymidylate synthetase levels and tumor weights were compared between these 2 groups. Results Blood total platinum levels rose as the number of doses increased, while the tumor tetrahydrofolate levels did not change. Neither the levels of thymidylate synthetase, nor tumor reduction, differed between the CDDP/5-fluorouracil and the 5-fluorouracil treatment groups. Conclusion No significant effect of intermittent low-dose CDDP therapy was seen on folic acid or thymidylate synthetase levels, or on tumor growth. The results of this study do not endorse the efficacy of intermittent low-dose CDDP as a modulator of 5-fluorouracil.     

Complete disappearance of metastatic lung tumors and mediastinal lymphnode in a case of hepatocellular carcinoma treated by low-dose 5-fluorouracil/cisplatin therapy

We report a case of complete disappearance of multiple lung metastases and mediastinal lymphnode metastasis by intravenous administration of 5-fluorouracil/cisplatin (FP) after operation for primary hepatocellular carcinoma (HCC). A 54-year-old male was diagnosed with HCC associated with alcoholic liver cirrhosis. He also had a single lung metastasis at the time of diagnosis. After hepatic resection for HCC, the metastatic tumor progressed and became multiple lesions with mediastinal lymphnode involvements. Low-dose FP therapy was performed. Then, 250 mg/m(2)/day of 5-fluorouracil was given intravenously for 5 days weekly by continuous infusion and 10 mg/m(2)/day of cisplatin by intravenous infusion. Both lung metastases and mediastinal lymphnode metastasis were decreasing after six cycles of this therapy. Because of alcoholism and liver damage, chemotherapy could not be continued. But all metastatic lesions were completely disappeared ten months after this therapy. Bone marrow suppression (grade 4) was observed during the chemotherapy but resolved by interruption of treatment. Low-dose FP therapy may well be useful for patients suffering from advanced HCC with distant metastasis.