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1.
Zhao Y  Liao Q  Zhu Z  Fu Q  Cai L  Zhu Y 《中华外科杂志》1999,37(3):144-145
探讨5-氟尿嘧啶能否通过胰十二指肠切除术后的残留胰腺组织进入胰液中,并达有效的治疗浓度,为胰腺为临床合理化疗提供理论依据。方法通过观察胰十二指肠切除术患者胰快速推注5-氟尿嘧啶后血液和胰液中药物动态分布及相关性,术后静脉一次性快速推注5-氟尿嘧啶1.0g/m^2,在给药前后按设计时间点分别采集静脉血和胰液,采用高效液相色谱法测定血浆和胰液5-氟尿嘧啶药物浓度,应用PCNONLIN程序程序计算共动态  相似文献   

2.
目的 本文通过观察化疗药物话导胰腺癌细胞凋亡过程中,P53和BCL-2基因表达量的变化,探讨化疗药物诱导胰腺癌细胞发生凋亡过程与相关基因表达的关系。方法 采用斑点杂交及激光密度扫描技术对化疗药物配伍;5-氟尿嘧喧(5-FU)、丝裂霉素(MMC)和表柔比星(E-ADM)诱导胰腺癌细胞株细胞发生凋亡过程中P53和BCL-2基因表达量的变化进行了检测分析。结果 化疗药物诱导胰腺癌细胞株细胞发生凋亡过程中  相似文献   

3.
氟尿嘧啶经胃左动脉和外周静脉化疗的药代动力学比较   总被引:39,自引:0,他引:39  
目的 探讨胃左动脉区域灌注化疗治疗胃癌的合理性。方法 比较氟尿嘧啶(5-FU)经胃左动脉和外周静脉给药后的药代动力学变化。结果 胃左动脉给药组的门静脉 血中5-FU浓度为外周静脉给药组的4 ̄200倍,而且5-FU高浓度的维持时间明显延长;癌组织和癌旁淋巴组织中5-FU水平分别为静脉给药组的19倍和23倍。结论 胃左动脉区域灌注化疗可明显增加癌肿局部的化疗药物浓度,提高化疗疗效。  相似文献   

4.
目的 探讨肿瘤坏死因子抗膀胱癌细胞作用的影响因素。方法 将肿瘤坏死因子α(TNF-α)和不同浓度的丝裂霉素(MC),顺铂(CDDP)以及干扰素α(IFN-α)作用于体外培养的膀胱癌细胞系BIU-87,用噻唑蓝(MTT)法测定细胞毒效果。结果 TNF-α对BIU-87细胞有明显的浓度依赖性抑制作用,MC(2.5~5.0mg/L)或IFN-α(2500U-5000U/ml)与TNF-α(10000U/  相似文献   

5.
胰腺癌细胞对化疗药物敏感性的测定   总被引:10,自引:0,他引:10  
目的 探讨人胰腺癌细胞株对常用化疗药物及其相互配伍的敏感性,为临床合理用药提供理论依据。方法 将人胰腺癌细胞株(P3、SW1990、Capan-2)细胞接种于96孔培养板,分别加入不同配伍及不同浓度的化疗药物,作用一定时间后采用噻唑蓝法(MTT法)测定其抗癌敏感性。结果 以5-氟脲嘧啶和丝裂霉素为基本的三联用药在抑制率相当的情况下,其组成中各药物剂量仅为单一用药剂量的1/50;联合用药方案中以5-  相似文献   

6.
区域性动脉灌注5-FU治疗急性坏死性胰腺炎   总被引:5,自引:0,他引:5  
作者自1992年8月至1993年12月,无选择地对19例急性坏死性胰腺炎患者采用Seldinger法,将Cordis导管置于胰腺病变的供血动脉内。如坏死病变位于胰头部,导管置于胃十二指肠动脉或胰十二指肠动脉;坏死病变限于胰体尾部,导管置于脾动脉或腹腔动脉;全胰散在性坏死病变,置管于腹腔动脉。经导管内区域性灌注5-FU为主的药物,自发病起20天内为灌注治疗时间。全组病例治疗后获得满意效果,并与以手术治疗为主的68例作对照,结果两组死亡率分别为10.5%、30.9%;器官功能衰竭发生率分别为5.3%、42.7%;继发性细菌感染发生率分别为5.3%、44.1%;有显著差异。作者认为区域性动脉灌注5-FU治疗急性坏死性胰腺炎是一种有效的疗法,且给延期手术,清除残留坏死胰腺组织提供了基础,术后病情恢复平衡。文中对方法、时间、作用和体会均作了详细的阐述。  相似文献   

7.
肝动脉结扎和肝动脉插管化疗治疗大肠癌肝转移   总被引:1,自引:0,他引:1  
对大多数不能切除的大肠癌肝转移病人行肝动脉结扎(HAL)和(或)肝动脉插管化疗(HAI)是目前国内外研究的方向之一,已获得初步疗效。肝脏转移癌与原发性肝癌一样,其血供也以肝动脉供血为主,故肝动脉插管和结扎同样是治疗肝转移癌的重要手段。HAI可使肿瘤组织直接接触高浓度化疗药物。对于某些全身清除率较大的化疗药物如5-FU、FUDR(5-氟脱氧尿苷)等,其局部浓度可提高50~400倍。此外,动脉内给药还可减少药物与血浆蛋白结合,降低其毒性。肝动脉结扎(HAL)致肿瘤局部缺血可提高肿瘤对化疗药物的敏感性…  相似文献   

8.
肝动脉栓塞加手术切除治疗大肝癌37例   总被引:5,自引:0,他引:5  
邹英华  蒋学祥 《普外临床》1997,12(3):133-135
作者报告37例大肝癌采用肝动脉栓塞(TAE)加手术切除的疗效及临床病理研究结果。37例肝癌直径5 ̄24cm(平均11.2cm),TAE与动脉灌注化疗同时进行,化疗药物包括氟尿嘧啶(5-FU),阿霉素(ADM)或表阿霉素(E-ADM),丝裂霉素(MMC)和顺铂(CDDP),多采用三种药物联合方案,肝动脉末梢栓塞剂采用国产或进口碘化油,用明胶海绵颗粒作近端栓塞。手术切除前进行1 ̄4次TAE,每次相隔4  相似文献   

9.
肿瘤细胞的甲硫氨酸依赖性对提高肿瘤化疗疗效的作用   总被引:8,自引:1,他引:7  
目的探讨肿瘤细胞的甲硫氨酸依赖性在提高肿瘤化疗疗效方面的作用及意义。方法将甲硫氨酸(Met)依赖性肿瘤细胞SGC7901、MCF7和非Met依赖性肿瘤细胞A549、A375培养于Met-Hcy+和Met+Hcy-培养基中,加入不同浓度的周期特异性化疗药5Fu或非周期特异性化疗药MMC;在细胞与药物接触不同时间段,用MTT比色法检测化疗药物的抑瘤率。结果Met-Hcy+中的5Fu对Met依赖性肿瘤细胞的抑瘤率较Met+Hcy-中的5Fu的抑瘤率有显著性提高;而5Fu对非Met依赖性肿瘤细胞的抑瘤率,在两种培养基间差异无显著性。MMC对Met依赖性、非Met依赖性肿瘤细胞的抑瘤率未因培养基的不同而差异有显著性。结论利用肿瘤细胞的Met依赖性,Met-Hcy+培养基可显著提高周期特异性化疗药(5Fu)对Met依赖性肿瘤细胞的抑瘤率,但不能提高周期非特异性化疗药(MMC)的抑瘤率。  相似文献   

10.
作者报告37例大肝癌采用肝动脉栓塞(TAE)加手术切除的疗效及临床病理研究结果。37例肝癌直径5~24cm(平均11.2Cm)。TAE与动脉灌注化疗同时进行。化疗药物括氟尿嘧啶(5-FU)、阿霉素(ADM)或表阿霉素(E-ADM)、丝裂霉素(MMC)和顺铂(CDDP)。多采用三种药物联合方案。肝动脉末梢栓塞剂采用国产或进口碘化油,用明胶海绵颗粒作近端栓塞。手术切除前进行1~4次TAE,每次相隔4~6周。17例AFP值增高者TAE后10例降至正常水平。肿瘤直径由平均11.2cm降至8.5cm(缩小26%)。栓塞后手术切除病理标本显示92%有肿瘤组织坏死,范围达40%~100%。1、2、3年生存率分别为80%、66.7%和53.3%。作者认为TAE加手术切除是大肝癌的有效治疗方法。  相似文献   

11.
The drug, 5-fluorouracil (5-FU), is thought to be efficacious in treating human pancreatic or biliary carcinomas; therefore, to determine the optimal dosage for chemotherapeutic use in these conditions, we performed this pharmacokinetic study in which we investigate the passage of various doses of intravenously administered 5-FU into the pancreatic juice of 11 patients with pancreatic or biliary carcinoma. Whenever possible, all 11 patients, who had undergone a pancreaticoduodenectomy and had an external drainage tube, received the following three regimens: (1) a bolus injection of 5-FU, 185 mg/m2 per day; (2) a continuous infusion of 5-FU, 185 mg/m2 per day over 48h (CIV-I), and (3) a continuous infusion of 5-FU, 370 mg/m2 per day over 48 h (CIV-II), with a sufficient wash-out period of 2 weeks between each regimen. The major findings were: (i) the percentage of the administered 5-FU dose excreted (pancreatic passage fraction; Fp) was strongly correlated with the total amount of pancreatic juice excreted over the 24-h period (Vp) of drug testing; (ii) the Fp per 100 ml Vp (Fp') was greater after the bolus treatment than after either CIV treatment; (iii) 90% of the 5-FU excreted into the pancreatic juice was present within 30min of the bolus injection; and (iv), the entire body clearance (CLtotal) of 5-FU was significantly lower after the bolus injection than after either CIV treatment. It was concluded that the Fp' value was dependent on the method of 5-FU administration, that a 5-FU bolus injection probably inundates the hepatic metabolic capacity, and that the Fp' of 5-FU largely depends on the patient's ability to metabolize the drug. Therefore, the efficacy of 5-FU as an anticancer agent appears to be time-rather than dose-dependent.  相似文献   

12.

Background

The impact of the addition of gemcitabine to 5-fluorouracil (5-FU) chemoradiation (CRT) on 5-year overall survival (OS) in resected pancreatic adenocarcinoma are presented with updated results of a phase III trial.

Methods

After resection of pancreatic adenocarcinoma, patients were randomized to pre- and post-CRT 5-FU versus pre- and post-CRT gemcitabine. 5-FU was provided continuously at 250 mg/m2/day, and gemcitabine was provided at 1000 mg/m2 weekly. Both were provided over 3 weeks before and 12 weeks after CRT. CRT was provided at 50.4 Gy with continuously provided 5-FU. The primary end point was survival for all patients and for patients with tumor of the pancreatic head.

Results

Four hundred fifty-one patients were eligible. Univariate analysis showed no difference in OS. Pancreatic head tumor patients (n = 388) had a median survival and 5-year OS of 20.5 months and 22% with gemcitabine versus 17.1 months and 18% with 5-FU. On multivariate analysis, patients on the gemcitabine arm with pancreatic head tumors experienced a trend toward improved OS (P = 0.08). First site of relapse local recurrence in 28% of patients versus distant relapse in 73%.

Conclusions

The sequencing of 5-FU CRT with gemcitabine as done in this trial is not associated with a statistically significant improvement in OS. Despite local recurrence being approximately half of that reported in previous adjuvant trials, distant disease relapse still occurs in ≥70% of patients. These findings serve as the basis for the recently activated EORTC/U.S. Intergroup RTOG 0848 phase III adjuvant trial evaluating the impact of CRT after completion of a full course of gemcitabine.  相似文献   

13.
The collagen-gel droplet embedded-culture drug sensitivity test (CD-DST), a chemosensitivity test, evaluate the efficacy of anticancer drugs and to was used clinically to thus plan rational postoperative chemotherapy for patients with pancreatic and biliary tract carcinomas. The CD-DST solves some problems inherent in other conventional assays. This method: (1) allows evaluation of four chemotherapeutic agents, using small quantities of cells (1 × 105 cells), (2) shows high primary culture success rates, (3) maintains the original growth characteristics of the cultured cells, (4) eliminates the effects of fibroblasts by employing image analysis, and (5) permits evaluation using physiologic drug concentrations. Primary cultures of tumor cell samples from all 25 patients with pancreatic or biliary tract carcinomas studied were successful. Against pancreatic carcinomas, the efficacy rates, assessed by CD-DST, of four anticancer drugs evaluated were: 25.0% for mitomycin (MMC), followed by 23.5% for adriamycin, 18.8% for 5-fluorouracil (5-FU), and 11.8% for cisplatin (CDDP). Against biliary tract carcinomas, the rates were highest for 5-FU and MMC (50.0%) and lowest for CDDP (25.0%). The efficacy rates for all four anticancer drugs evaluated were higher against biliary tract carcinomas than against pancreatic carcinomas. Tumor cultures from 10 of 17 patients with pancreatic cancer and 3 of 8 patients with biliary tract cancer showed no sensitivity to any of the drugs tested. The in-vitro results with CD-DST suggest the risk of administering non-selective postoperative chemotherapy to patients with pancreatic and biliary tract carcinomas, and emphasize the importance of carefully selecting effective chemotherapeutic agents based on adequate chemosensitivity testing. Received for publication on July 29, 1998; accepted on Aug. 13, 1998  相似文献   

14.
BACKGROUND: Based on a 2-year survival of 43%, the Gastrointestinal Tumor Study Group (GITSG) recommended adjuvant 5-FU-based chemoradiation for resected patients with adenocarcinoma of the pancreatic head. Here we report improved survival over the GITSG protocol with a novel adjuvant chemoradiotherapy based on interferon-alpha (IFNalpha). METHODS: From July 1993 to September 1998, 33 patients with adenocarcinoma of the pancreatic head underwent pancreaticoduodenectomy (PD) and subsequently went on to adjuvant therapy (GITSG-type, n = 16) or IFNalpha-based (n = 17) typically given between 6 and 8 weeks after surgery. The latter protocol consisted of external-beam irradiation at a dose of 4,500 to 5,400 cGy (25 fractions per 5 weeks) and simultaneous three-drug chemotherapy consisting of (1) continuous infusion 5-FU (200 mg/m2 per day); (2) weekly intravenous bolus cisplatin (30 mg/m2 per day); and (3) IFNalpha (3 million units subcutaneously every other day) during the 5 weeks of radiation. This was then followed by two 6-week courses of continuous infusion 5-FU (200 mg/m2 per day, given weeks 9 to 14 and 17 to 22). Risk factors for recurrence and survival were compared for the two groups. RESULTS: A more advanced tumor stage was observed in the IFNalpha-treated patients (positive nodes and American Joint Committee on Cancer [AJCC] stage III = 76%) than the GITSG group (positive nodes and stage III = 44%, P = 0.052). The 2-year overall survival was superior in the IFNalpha cohort (84%) versus the GITSG group (54%). With a mean follow-up of 26 months in both cohorts, actuarial survival curves significantly favored the IFNalpha group (P = 0.04). CONCLUSIONS: With a limited number of patients, this phase II type trial suggests better survival in the interferon group as compared with the GITSG group even though the interferon group was associated with a more extensive tumor stage. The 2-year survival rate in the interferon group is the best published to date for resected pancreatic cancer. The interferon/cisplatin/5-FU-based adjuvant chemoradiation protocol appears to be a promising treatment for patients who have undergone PD for adenocarcinoma of the pancreatic head.  相似文献   

15.
OBJECTIVE: This study was designed to evaluate prospectively survival after pancreaticoduodenectomy for pancreatic adenocarcinoma, comparing two different postoperative adjuvant chemoradiation protocol to those of no adjuvant therapy. SUMMARY BACKGROUND DATA: Based on limited data from the Gastrointestinal Tumor Study Group, adjuvant chemoradiation therapy has been recommended after pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancrease. However, many patients continue to receive no such therapy. METHODS: From October 1991 through September 1995, all patients with resected, pathologically confirmed adenocarcinoma of the head, neck, or uncinate process of the pancreas were reviewed by a multidisciplinary group (surgery, radiation oncology, medical oncology, and pathology) and were offered three options for postoperative treatment after pancreaticoduodenectomy: 1) standard therapy: external beam radiation therapy to the pancreatic bed (4000-4500 cGy) given with two 3-day fluorouracil (5-FU) courses and followed by weekly bolus 5-FU (500 mg/m2 per day) for 4 months; 2) intensive therapy: external beam radiation therapy to the pancreatic bed (5040-5760 cGy) with prophylactic hepatic irradiation (2340-2700 cGy) given with and followed by infusional 5-FU (200 mg/m2 per day) plus leucovorin (5 mg/m2 per day) for 5 of 7 days for 4 months; or 3) no therapy: no postoperative radiation therapy or chemotherapy. RESULTS: Pancreaticoduodenectomy was performed in 174 patients, with 1 in-hospital death (0.6%). Ninety-nine patients elected standard therapy, 21 elected intensive therapy, and 53 patients declined therapy. The three groups were comparable with respect to race, gender, intraoperative blood loss, tumor differentiation, lymph node status, tumor diameter, and resection margin status. Univariate analyses indicated that tumor diameter < 3 cm, intraoperative blood loss < 700 mL, absence of intraoperative blood transfusions, and use of adjuvant chemoradiation therapy were associated with significantly longer survival (p < 0.05). By Cox proportional hazards survival analysis, the most powerful predictors of outcome were tumor diameter, intraoperative blood loss, status of resection margins, and use of postoperative adjuvant therapy. The use of postoperative adjuvant chemoradiation therapy was a predictor of improved survival (median survival, 19.5 months compared to 13.5 months without therapy; p = 0.003). The intensive therapy group had no survival advantage when compared to that of the standard therapy group (median survival, 17.5 months vs. 21 months, p = not significant). CONCLUSIONS: Adjuvant chemoradiation therapy significantly improves survival after pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Based on these survival data, standard adjuvant chemoradiation therapy appears to be indicated for patients treated by pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Intensive therapy conferred no survival advantage over standard therapy in this analysis.  相似文献   

16.
Background: Although the survival benefit of hepatic resection for colorectal metastasis has been established, some controversy remains regarding the significance of adjuvant chemotherapy after hepatic resection. Methods: One hundred thirty-two consecutive patients who had liver resection for colorectal metastasis at our hospital between 1980 and 1997 were studied. After curative hepatic resection, 37 patients underwent systemic chemotherapy, administered orally or intraportally. Forty patients had no adjuvant chemotherapy. The chemotherapeutic agents used for oral administration were uracil and Tegafur or Tegafur alone. Mitomycin C (MMC) or 5-FU was used for IV chemotherapy. Combinations of 5-FU/leucovorin or MMC/5-FU (doxorubicin) were used for regional chemotherapy. Univariate and multivariate analyses were applied to test the significance of adjuvant chemotherapy for patient survival or disease-free survival. Results: Overall 5-year survival was 42.2% (95% CL: 31.2%, 53.2%). Among the possible prognostic factors studied, univariate analysis showed a significant difference in survival based on the number of tumors and lymph node metastases in the hepatic hilum. There was a significant difference in disease-free survival based on adjuvant chemotherapy and lymph node metastasis. The multivariate analysis for patient survival selected four prognostic factors (P<.05), including adjuvant chemotherapy, lymph node metastasis, disease-free interval, and tumor size. The multivariate analysis for disease-free survival selected adjuvant chemotherapy, lymph node metastasis, and disease-free interval as significant factors. The most common recurrence site was remnant liver, regardless of adjuvant chemotherapy. Conclusions: Adjuvant chemotherapy significantly improved survival and disease-free survival after hepatic resection for colorectal metastases. It did not decrease recurrence rate in the remnant liver.Presented at the 51st Annual Cancer Symposium of The Society of Surgical Oncology, San Diego, California, March 26–28, 1998.  相似文献   

17.
目的 探讨全身性热化疗治疗晚期胰腺癌的效果,以及化疗药物在此过程中代谢的变化。方法 将42例晚期胰腺癌病人分成2组,分别接受全身性热化疗和单纯化疗后,比较二者的疗效、不良反应及5 FU的药代动力学指标。结果 实验组具有较好的疗效,不良反应的发生率随之提高,其体内化疗药物的相对浓度升高。结论 全身性热化疗是一种有效的治疗晚期胰腺癌的方法,其机理与化疗药物在体内有效浓度的增加有密切的关系。  相似文献   

18.
联合化疗治疗晚期胰腺癌的疗效分析   总被引:2,自引:0,他引:2  
目的探讨吉西他滨和5-氟尿嘧啶联合治疗晚期胰腺癌的疗效和可能的影响机制。方法实验组22例接受吉西他滨、5-氟尿嘧啶和四氢叶酸联合化疗,对照组21例接受5-氟尿嘧啶 四氢叶酸联合化疗,比较他们的近期疗效、疾病相关症状改善状况和不良反应。通过高效液相色谱技术检测第1、5天时2组病人5-氟尿嘧啶的血浆浓度和半衰期。结果实验组病人的近期疗效、疾病相关症状改善均好于对照组,但不良反应也增加。实验组病人血浆中5-氟尿嘧啶的血药浓度增高,半衰期延长,上述变化贯穿于5-氟尿嘧啶的整个治疗过程。结论吉西他滨可改善5-氟尿嘧啶治疗晚期胰腺癌的疗效,其机制与它能长时间的提高5-氟尿嘧啶在体内的有效浓度有关。  相似文献   

19.
OBJECTIVE: To clarify the relationship between intratumoral dihydropyrimidine dehydrogenase (DPD) expression and response to 5-fluorouracil (5-FU) liver perfusion chemotherapy (LPC) in pancreatic cancer patients, we evaluated DPD expression immunohistochemically in resected pancreatic cancer tissues. SUMMARY BACKGROUND DATA: Pancreatic cancer is considered a disease with a poor prognosis even if aggressive resection is performed. One of the main causes of death is hepatic metastasis soon after surgery. As a treatment, we have assessed adjuvant LPC via the portal vein using 5-FU just after pancreatectomy for advanced pancreatic cancer since 1994. However, the results remain unsatisfying. METHODS: Sixty-eight resected specimens were obtained from patients with pancreatic cancer from 1988 to 2000. Formalin-fixed paraffin-embedded tissues were immunostained with polyclonal anti-DPD antibody. The relation between intratumoral DPD expression and the prognoses of pancreatic cancer patients was investigated statistically. RESULTS: Of the 68 tumors studied, 27 carcinomas (39.7%) were DPD(+), and 41 (60.3%) were DPD(-). In the DPD(+) group, there was no significant difference between the LPC(+) and LPC(-) subgroups, whereas in the DPD(-) group the LPC(+) subgroup showed a significantly higher survival rate than the LPC(-) subgroup. Moreover, in the LPC(+) group, overall survival in the DPD(-) subgroup was significantly better than in the DPD(+) subgroup. CONCLUSIONS: An immunohistochemical evaluation of intratumoral DPD expression might be useful in predicting responsiveness to 5-FU-based chemotherapy in pancreatic cancer patients. In the DPD(-) group, liver perfusion chemotherapy using 5-FU via the portal vein is effective adjuvant therapy for pancreatic cancer once pancreatectomy has been performed.  相似文献   

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