新辅助治疗方法治疗食管鳞状上皮细胞癌27例

目的研究连续输注低剂量5-FU和顺铂在食管鳞状上皮细胞癌的治疗中的作用。方法在本研究组中有27例食管鳞状上皮细胞癌患者。连续输注低剂量5—FU（350mg／m2／d）,共输30d;低剂量顺铂（7．5mg／m2／d）每周输5d,共输4周。所有患者化疗后均执行手术治疗。结果22例患者完成了化疗全过程,5例由于复发性血栓性静脉炎（n=1）、4级呕吐（n=1）、不配合（n=3）;血液学和肝脏毒性5例;15例患者出现血栓性静脉炎;吞咽困难得到改善的有18例（66．7％）;手术切除率达85．2％,生存中值达16个月,3年生存率为45．5％。结论连续输注低剂量的的5-FU和顺铂不仅可以提高化疗效果,提高其治愈率,还可以耐受药物较小的毒性反应。     

Repetitive short-course hepatic arterial infusion chemotherapy with high-dose 5-fluorouracil and cisplatin in patients with advanced hepatocellular carcinoma

BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) has often been selected as a therapeutic option for patients with advanced hepatocellular carcinoma (HCC). The objective of the current study was to evaluate the efficacy and safety of repetitive HAIC with high-dose 5-fluorouracil (5-FU) and cisplatin given for 3 days in patients with advanced HCC. METHODS: Between January 2001 and December 2004, a total of 41 patients with unresectable advanced HCC were enrolled. The patients underwent HAIC via the implantable port system with 5-FU (at a dose of 500 mg/m(2) on Days 1-3) and cisplatin (at a dose of 60 mg/m(2) on Day 2) every 4 weeks. Tumor response was assessed at the end of every 3 cycles. RESULTS: The median age of the patients was 53 years and 34 patients (82.9%) had evidence of portal vein thrombosis. In total, 230 cycles of HAIC were administered to the 41 patients, with a median of 6 cycles given (range, 1-14 cycles). Nine patients (22.0%) achieved a partial response and 14 patients (34.1%) had stable disease. The median time to disease progression and overall survival were 7.0 months and 12.0 months, respectively. The overall survival was found to be significantly longer in the successful disease control group (patients with a complete response, partial response, and stable disease) than in the disease progression group (median of 14.0 months vs 6.0 months; P < .001). Adverse reactions were tolerable and successfully managed with conservative treatment. CONCLUSIONS: HAIC with high-dose 5-FU and cisplatin given for 3 days achieved effective and safe results in patients with advanced HCC. Therefore, repetitive short-course HAIC with high-dose 5-FU and cisplatin may be useful as an alternative therapeutic option for patients with advanced HCC.     

Severe enteropathy among patients with stage II/III colon cancer treated on a randomized trial of bolus 5-fluorouracil/leucovorin plus or minus oxaliplatin: a prospective analysis

BACKGROUND: Cases of severe gastrointestinal toxicity were monitored prospectively during NSABP C-07, a randomized clinical trial of adjuvant therapy for patients with stage II/III colon cancer. METHODS: Patients were treated with weekly bolus 5-fluorouracil (5-FU) and leucovorin (FL; "Roswell Park Regimen") or the same regimen plus oxaliplatin (FLOX). RESULTS: Of 1857 patients, 79 (4.3%) developed a syndrome of bowel wall injury (BWI, small or large) characterized by hospitalization for the management of severe diarrhea or dehydration and radiographic or endoscopic evidence of bowel wall thickening or ulceration. Fifty-one (64.6%) of these adverse events occurred in patients treated with FLOX and 28 (35.4%) in those treated with FL (P < .01). Enteric sepsis (ES), characterized by grade 3 or greater diarrhea and grade 4 neutropenia with or without proven bacteremia occurred in 22 patients treated with FLOX, versus 8 in those treated with FL (P = .01). Patients >60 years were at higher risk for BWI after treatment with FLOX (6.7%) versus treatment with FL (2.9%, P < .01). Female patients had a higher incidence of BWI with FLOX (9.1%) than with FL (3.9%, P < .01). Severe gastrointestinal toxicity usually occurred during the third or fourth week on the first cycle of therapy, required hospitalization, and was managed with fluids, antidiarrheals, and antibiotics. There were 5 deaths (0.3%) due to enteropathy, 2 related to ES and 3 related to both BWI and ES. Seventy-one percent of patients resumed treatment with FL after recovery. CONCLUSIONS: Patients treated with adjuvant FL should be closely monitored for diarrhea and aggressively managed, especially if oxaliplatin has been added to the regimen. Society.     

滤过手术联合干扰素治疗青光眼临床观察

为观察滤过手术联合ａ干扰素，治疗难治性青光眼的疗效，将３４例（４２只眼）难治性青光眼随机分为ａＩＦ治疗组２２只眼与５ＦＵ对照组２０只眼。治疗组术中、术后，采用ａＩＦ球内（玻璃体内）或结膜下注射，对照组术后采用５ＦＵ结膜下注射。术后随访５～１４个月。结果ａＩＦ治疗组手术成功率为８１８％（１８／２２）５ＦＵ对照组为８５％（１７／２０），Ｐ＞００５。功能性滤过泡眼数，ａＩＦ治疗组为１７／２２，５ＦＵ对照组为１６／２０。治疗组未见明显全身和局部副作用。结论：ａＩＦ能促进滤过泡的形成，提高青光眼滤过手术的成功率，效果同５ＦＵ。     

Impacts of fluorouracil‐metabolizing enzymes on the outcomes of patients treated with S‐1 alone or S‐1 plus cisplatin for first‐line treatment of advanced gastric cancer

A phase III trial of S‐1 plus cisplatin (SP) versus S‐1 alone, for first‐line treatment of advanced gastric cancer (SPIRITS trial), has shown that overall survival was better in patients treated with SP than with S‐1 alone. In the present retrospective biomarker study, we aimed to develop a methodology to identify the patients with advanced gastric cancer who would respond better to S‐1 alone than SP. We studied 120 patients who received S‐1 alone or SP for first‐line chemotherapy for advanced gastric cancer, and quantitatively evaluated mRNA levels of thymidylate synthase (TS), thymidine phosphorylase (TP), orotate phosphoribosyltransferase (OPRT), dihydropyrimidine dehydrogenase, vascular endothelial growth factor‐A, and epidermal growth factor receptor in paraffin‐embedded specimens of primary tumors. Multivariate survival analysis in patients who received S‐1 monotherapy (66 patients) demonstrated that low TP expression (hazard ratio: 2.55 (95% CI: (1.33 to 4.89)), low TS (2.71 (1.36 to 5.37)), and high OPRT (0.33 (0.13 to 0.86)) were significant predictors of long overall survival. In patients with lower expression of both TP and TS (n = 23) than their cutoff values, the S‐1 alone group (n = 15) had longer overall survival than the SP group (n = 8; median overall survival, 18.2 months vs. 9.4 months), whereas the frequency of overall adverse events in the S‐1 alone group tended to be lower than that in SP group. Our results suggest that these biomarkers are useful for selection of patients with advanced gastric cancer in whom treatment with S‐1 alone will yield survival benefit.     

薏苡仁酯配合化学药物治疗晚期鼻咽癌的临床研究

目的 :探讨薏 以艹 仁酯 (coixenolide,CXL)配合 PFB方案治疗晚期鼻咽癌 (NPC)的疗效与机制。方法 :将 60例 期伴远处转移的 NPC患者随机分为两组。对照组单纯化疗 ,试验组化疗加 CXL。两组的化疗方案、剂量及疗程均相同。顺铂 (DDP) 2 0 mg/(m2· d) ,静脉滴注 ,第 1～ 5天 ;5-氟尿嘧啶 (5- Fu) 50 0 mg/(m2· d) ,静脉滴注 ,第 1～ 5天 ;博来霉素(BLM) 7mg/(m2 · d) ,肌肉注射 ,第 1、5天 ;共 3个疗程。试验组加滴 CXL注射液 2 0 0 ml/次 ,1次 /d,直至化疗结束。同时 ,在治疗前后采用 APAAP、MTT方法分别检测 T淋巴细胞及其亚群、NK细胞和 IL- 2活性。结果 :对照组有效率63.3% ,试验组 86.7% ,差异显著 (P<0 .0 5)。化疗后对照组 CD3 、CD4、CD4、/CD8下降明显 (前后比较 ,P<0 .0 5或0 .0 1 ) ,试验组则回升 (P<0 .0 5或 0 .0 1 ) ,并高于对照组 (P<0 .0 1 )。NK细胞和 IL- 2活性也显示相似的变化。随访 1年 ,对照组无瘤生存 0例 ,病情稳定 1 6例 ,恶化 7例 ,死亡 7例 ;试验组分别是 5、2 0、3、2例 ,优于对照组 (P<0 .0 2 5)。结论 :CXL配合 PFB方案提高晚期 NPC的疗效。可能的机理是 ,CXL增加癌细胞对化疗药物的敏感性 ,或直接抑制癌细胞的增殖 ,以及通过调节免疫功能促进抗癌     

Prediction of chemotherapeutic response of colorectal liver metastases with dynamic gadolinium-DTPA-enhanced MRI and localized 19F MRS pharmacokinetic studies of 5-fluorouracil

Systemic chemotherapy is effective in only a subset of patients with metastasized colorectal cancer. Therefore, early selection of patients who are most likely to benefit from chemotherapy is desirable. Response to treatment may be determined by the delivery of the drug to the tumor, retention of the drug in the tumor and by the amount of intracellular uptake, metabolic activation and catabolism, as well as other factors. The first aim of this study was to investigate the predictive value of DCE-MRI with the contrast agent Gd-DTPA for tumor response to first-line chemotherapy in patients with liver metastases of colorectal cancer. The second aim was to investigate the predictive value of 5-fluorouracil (FU) uptake, retention and catabolism as measured by localized (19)F MRS for tumor response to FU therapy. Since FU uptake, retention and metabolism may depend on tumor vascularization, the relationship between (19)F MRS and the DCE-MRI parameters k(ep), K(trans) and v(e) was also examined (1). In this study, 37 patients were included. The kinetic parameters of DCE-MRI, k(ep), K(trans) and v(e), before start of treatment did not predict tumor response after 2 months, suggesting that the delivery of chemotherapy by tumor vasculature is not a major factor determining response in first-line treatment. No evident correlations between (19)F MRS parameters and tumor response were found. This suggests that in liver metastases that are not selected on the basis of their tumor diameter, FU uptake and catabolism are not limiting factors for response. The transfer constant K(trans), as measured by DCE-MRI before start of treatment, was negatively correlated with FU half-life in the liver metastases, which suggests that, in metastases with a larger tumor blood flow or permeability surface area product, FU is rapidly washed out from the tumor.     

5-氟尿嘧啶区域动脉灌注对SAP大鼠炎性因子的影响

【目的】探讨5-氟尿嘧啶区域动脉灌注对重症急性胰腺炎(SAP)大鼠炎性因子的影响及其与胰腺病理损害程度的相关性。【方法】SD大鼠64只,随机分为假手术组(A组),SAP组(B组),5-氟尿嘧啶外周静脉注射组(C组),5-氟尿嘧啶区域动脉灌注组(D组)。测定各组大鼠的血清淀粉酶(Amy),各组动物血中白细胞介素-1(IL-1)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的含量及胰腺病理学变化。【结果】①制成SAP模型后,各组Amy水平显著上升,5-氟尿嘧啶治疗后可使Amy下降,其中5-氟尿嘧啶区域动脉灌注组下降更为明显。②5-氟尿嘧啶治疗可使血中IL-1、IL-6、TNF-α的含量显著降低(P<0.05),胰腺病理损害程度显著减轻(P<0.05),5-氟尿嘧啶区域动脉灌注组作用更强。【结论】①SAP时,应用5-氟尿嘧啶,可降低血中IL-1、IL-6、TNF-α的含量,减轻胰腺病理损害,是治疗SAP的方法之一。②区域动脉灌注是治疗SAP的增效途径。