术前氟铁龙化疗对大肠癌组织TP/PD-ECGF表达和血管生成的影响

目的　研究术前氟铁龙化疗 ,对大肠癌胸苷磷酸化酶 /血小板衍化内皮细胞生长因子 (TP/PD -ECGF)表达和肿瘤组织微血管密度 (MVD)的影响。方法　对 2 5例术前应用氟铁龙化疗的大肠癌和 2 5例术前未化疗的大肠癌组织 ,采用免疫组织化学检测TP/PD -ECGF表达及微血管密度。结果　术前化疗组TP/PD -ECGF表达阳性率为 3 2 .0 % ,对照组为 60 .0 % ;化疗组和对照组MVD值分别为 3 4.7± 14 .0和 62 .3± 10 .8;两者有显著性差异。结论　术前氟铁龙化疗能使TP/PD -ECGF活性降低 ,从而抑制大肠癌的肿瘤血管生成     

晚期乳腺癌术前区域性动脉灌注化疗后微血管密度及微淋巴管密度的变化

目的探讨术前区域动脉灌注化疗及全身静脉化疗对晚期乳腺癌微血管密度（MVD）、微淋巴管密度（MLVD）的影响。方法将76例晚期乳腺癌患者随机分为2组，术前动脉灌注化疗组35例，术前全身静脉化疗组41例，选其中25例化疗前的乳腺癌患者作对照组。采用免疫组化sP法，用CD34、VEGFR3抗体对3组乳腺癌组织标本进行MVD、MLVD检测。结果术前动脉灌注化疗组的MVD为36．05±13．64，全身静脉化疗组为49．92±12．90，对照组为60．38±13．54，各组间比较（P〈0．01）；术前动脉灌注化疗组的MLVD为6．62±3．70，全身静脉化疗组为9．96±4．57，对照组为11．30±5．32，动脉灌注化疗组与对照组比较显著下降（P〈0．01），与静脉化疗组比较差异有统计学意义（P〈0．05），静脉化疗组与对照组比较差异无统计学意义（P〉0．05）。结论术前区域性动脉灌注化疗比全身静脉化疗更能有效降低肿瘤组织及其周边组织内MVD和MLVD，从而抑制肿瘤细胞生长，减少肿瘤转移的机会。     

术前希罗达化疗对大肠癌组织TP／PD-ECGF表达和血管生成的影响

目的研究术前希罗达化疗对大肠癌胸苷磷酸化酶/血小板衍化内皮细胞生长因子(TP/PD-ECGF)和肿瘤组织微血管密度(MVD)的影响.方法对30例术前应用希罗达化疗的大肠癌和30例术前未化疗的大肠癌组织,采用免疫组织化学检测TP/PD-ECGF表达及微血管密度.结果术前化疗组TP/PD-ECGF表达阳性率为35.0%,对照组为63.0%;化疗组和对照组MVD值分别为37.4±18.0和65.8±12.5,差异有显著性.结论术前化疗能使TP/PD-ECGF活性降低,从而抑制大肠癌的肿瘤血管生成.     

大肠癌c-met、p53的表达与血管生成的关系

目的　探讨c met、p5 3在大肠癌中表达以及与微血管密度 (MVD)之间的关系。方法　应用免疫组化SP法检测 5 1例大肠癌、16例腺瘤、16例正常组织中c met、p5 3、MVD的表达。结果　大肠癌中c met、p5 3、MVD的阳性表达与癌组织的分期、淋巴结转移及远处转移有关 (P <0 .0 5 )。c met( )和p5 3 ( )的组织中MVD值 ( 3 2 .98± 10 .0 7,3 5 .44± 10 .42 )显著高于c met( -)和p5 3 ( -)者( 17.2 9± 8.65 ,2 2 .17± 9.5 4) (P <0 .0 5 )。c met、p5 3的表达与MVD计数均显著相关 (P <0 .0 5 )。结论　c met、p5 3均参与调控大肠癌的微血管生成。     

大肠癌血管内皮生长因子的表达与转移的相关性研究

目的　探讨大肠癌组织中血管内皮生长因子 (VEGF)的表达与间质微血管密度 (MVD)及转移的相关性。方法　应用免疫组化 S- P法 ,检测 87例大肠癌中 VEGF的表达 ,同时选用 CD34进行微血管标记并计数。结果　大肠癌中 VEGF的表达与间质 MVD呈正相关 (r=0 .70 2 )。转移组 VEGF的表达与 MVD均高于未转移组 (P<0 .0 5 )。结论　 VEGF的表达及 MVD增高与大肠癌转移有关 ,可作为大肠癌转移危险度的预测     

局部晚期食管下段癌术前动脉灌注化疗临床疗效观察

目的:探讨局部晚期食管下段癌术前动脉灌注化疗的临床疗效.方法:64例局部晚期食管下段癌患者随机分为两组:术前灌注化疗组及直接手术组.前者术前行选择性动脉灌注化疗:表柔比星60-80mg,顺铂40-60mg,5-FU 750-1000mg.化疗后2周左右接受手术治疗.观察动脉灌注化疗不良反应、组织学疗效,并比较两组手术切除率及手术并发症.结果:动脉灌注化疗不良反应主要表现为胃肠道反应和骨髓抑制,均为Ⅱ度以下.灌注化疗组手术切除率为100％,R0切除率为87.5％ (28/32),均高于直接手术组(P＜0.05),后者手术切除率为78.1％ (25/32),R0切除率为62.5％(20/32).术后并发症两组之间无统计学差异(P＞0.05).术前灌注化疗组术后病理分期较术前降低,其中Ⅱ期病例明显增多.结论:局部晚期食管下段癌术前选择性动脉灌注化疗可降低临床分期,提高手术切除率.     

动脉灌注化疗栓塞对宫颈癌VEGF及MVD的影响

目的探讨动脉灌注化疗栓塞对子宫颈癌血管内皮生长因子(VEGF)表达及微血管密度(MVD)的影响。方法对36例局部晚期宫颈癌患者动脉灌注化疗前后的肿瘤组织,用CD34对VEGF表达进行测定,并进行MVD计数。结果本组患者动脉灌注化疗栓塞前及后2~3周VEGF阳性表达率分别为75%(27/36)、30.6%(11/36),MVD计数明显降低,差异均有显著性意义(P<0.001)。结论动脉灌注化疗能降低宫颈癌组织VEGF的表达,减少MVD计数,提示动脉灌注化疗可能调节宫颈癌的分化程度,降低宫颈癌的恶性潜能,减少术后转移。     

大肠癌组织中Survivin表达与血管生成、细胞增殖的关系

目的　探讨大肠癌组织中Survivin表达与血管生成、细胞增殖的关系。方法　采用原位杂交方法和免疫组织化学方法 ,对 46例大肠癌、2 2例大肠腺瘤和 10例大肠正常组织进行SurvivinmRNA和PCNA检测 ,并计数微血管密度 (MVD)。结果　大肠癌组织中SurvivinmRNA、PCNA指数和MVD均显著高于大肠腺瘤和大肠正常组织 (P <0 .0 5 )。SurvivinmRNA表达阳性组中 ,MVD和PCNA指数均明显高于SurvivinmRNA阴性组 (P <0 .0 5 )。结论　Survivin在大肠癌组织中表达上调 ,并与血管生成和细胞增殖关系密切 ,提示Survivin对大肠癌的发生发展起重要作用     

HIF-1α和iNOS在大肠癌组织血管形成中的作用

目的　探讨缺氧诱导因子 1α(HIF 1α)和诱导型一氧化氮合酶 (iNOS)在大肠癌血管形成中的作用。方法　采用免疫组化S P法 ,检测 62例大肠癌组织及 10例癌旁正常组织中HIF 1α和iNOS蛋白的表达 ,并用CD3 4标记血管内皮细胞 ,计算微血管密度 (MVD )。结果　 62例大肠癌组织中 ,HIF 1α、iNOS蛋白阳性表达率分别为 43 .5 % ( 2 7/62 ) ,5 6.5 % ( 3 5 /62 ) ,MVD平均值为 2 8.3± 17.5。HIF 1α、iNOS蛋白阳性表达率及MVD与癌组织Dukes分期显著相关 (P均 <0 .0 5 )。HIF 1α与iNOS表达一致符合率为 5 1.6% ( 3 2 /62 ) ,两者表达显著相关 (P <0 .0 5 )。HIF 1α、iNOS均阳性的大肠癌组织MVD高于两者均为阴性者 ,有显著性差异 (P <0 .0 5 )。结论　大肠癌组织存在HIF 1α蛋白的过表达 ,HIF 1α诱导iNOS蛋白表达 ,协同促进肿瘤新血管形成。HIF 1α、iNOS及MVD的测定可作为判断大肠癌转移潜能的重要指标     

胸苷磷酸化酶在癌组织中表达的研究

目的　研究胸苷磷酸化酶 (TP)在不同种类癌组织中的表达 ,探讨TP与癌组织血管生成的关系。方法　采用免疫组织化学方法检测 2 5 1例癌组织和相对应的 92例正常组织TP和微血管密度 (MVD)的表达。癌组织包括 :胃癌 4 8例 ,大肠癌 5 3例 ,乳腺癌 4 7例 ,宫颈癌 5 6例 ,肺癌 4 7例 ;正常组织包括 :胃 2 5例 ,大肠 2 5例 ,宫颈 17例 ,肺 2 5例。分析癌组织和正常组织TP表达差异 ,及癌组织TP表达与癌组织MVD的关系。结果　胃癌、大肠癌、乳腺癌、宫颈癌和肺癌的TP表达阳性率分别为6 4 .6 %、6 7.9%、80 .9%、82 .1%和 6 3.8%。癌组织的TP表达阳性率显著高于正常组织 (P =0 .0 0 0 0 )。癌组织TP表达与胃癌、大肠癌、乳腺癌、宫颈癌的MVD值关系密切 (P <0 .0 0 1)。结论　TP在胃癌、大肠癌、乳腺癌、宫颈癌和肺癌组织中过度表达 ,并对胃癌、大肠癌、乳腺癌和宫颈癌的血管生成有明显促进作用。     

超选择子宫动脉与外周静脉灌注化疗宫颈癌组织内铂浓度的研究

Objective:The present study is to compare pharmacokinetics difference of carboplatin by using ultraselection uterine artery with by using peripheral vein in cervical cancer. Methods:Thirteen patients with locally advanced cervical cancer who had been proved by pathobiology were randomly divided into two groups:the ultraselection uterine artery group (group A, n=6) and the peripheral vein (group B, n=7). Carboplatin was administered by infusing into artery or vein in both groups at the dosage of 300 mg/m2. Tissues from the cervical tumor were collected at different times after infusion in both groups and then analyzed. Results:The peak concentration of platinum in tumor tissue was about 2.79 times higher in group A than that of group B (P<0.05). The platinum concentrations in tumor in group A reached its peak levels immediately after infusion. But, group B had delayed time. While, for the time point of 0 min, when the administration finished immediately, the platinum concentration in tumor was significantly higher when compared with group B (P < 0.05). The tumor tissue area under the concentration (AUC) of carboplatin was about 2 times higher in group A than that of group B (P < 0.05). Conclusion:We observed the pharmacological advantages of chemotherapy by using ultraselection uterine artery administration of chemo-therapeutic agent carboplatin in tumor tissue which provided theoretical basis and laboratory parameters of the intra-arterial chemotherapy for gynecologic malignancy.     

Prognostic study of preoperative serum levels of CEA and CA 19-9 in colorectal cancer

PURPOSE: Carcinoembrionic Antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) are the most frequently used tumor markers in the clinical setting of colorectal cancer. The aim of this study is to evaluate the prognostic value of preoperative serum levels of CEA and CA 19-9 in colorectal cancer patients. METHODS: Serum levels of CEA and CA 19-9 were examined in 586 patients with colorectal cancer. Cut-off levels were calculated at reference value:<2.5 ng/mL (group A) versus >2.5 ng/mL (group B) for CEA and, <37 U/mL (group A) versus >37 U/mL (group B) for CA 19-9. RESULTS: According to tumor progression, each marker tended to show a higher level. Group A showed a significantly better prognosis than group B in both CEA and CA 19-9. In Dukes classification A, B and C, only CEA showed a better prognosis in group A than group B. At the time of recurrence compared to the pre-operative point, the CEA and CA 19-9 levels were significantly higher in both group A and B, however. In relation to the necessity of adjuvant chemotherapy (5-FU containing regimen) in Dukes A, the cases without adjuvant chemotherapy in group B of CEA showed a poor prognosis. CONCLUSION: The measurement of preoperative serum CEA and CA 19-9 is useful for prognostic prediction in colorectal cancer. Cut-off levels calculated at the reference value reflect the prognosis in this study. Especially, preoperative CEA reveals a potential high risk group in Dukes A which should be carefully treated by adjuvant chemotherapy to avoid recurrence.     

Preoperative superselective intraarterial chemotherapy in the combined treatment of gastric-carcinoma

146 patients were included in this prospective, randomized study: 50 patients were treated with surgery alone (S), 49 patients received pre-operative intravenous (systemic) chemotherapy (IVCH) and 47 patients received pre-operative superselective intra-arterial chemotherapy (IACH). Left gastric and right gastroepiploic arteries were catheterized for IACH. After IACH a measurable tumor response was registered in 87.1% of the patients; in 61.6% no residual tumor was found in the resected stomach. IVCH produced no survival benefit compared to surgery alone. IACH plus S improved 3-year survival relative to surgery alone (89.3+/-2.1% vs 35.5+/-4.9%; p<0.01). Projected 5-year survival in the IACH+S group is 78.1% vs. 30.1% with surgery alone (p<0.01). IACH provided substantial survival benefit when used as a component of combined modality gastric cancer treatment.     

Biodegradable mitomycin C microspheres given intra-arterially for inoperable hepatic cancer. With particular reference to a comparison with continuous infusion of mitomycin C and 5-fluorouracil

Thirty-two patients with inoperable hepatic cancer underwent intra-arterial hepatic infusion using mitomycin C (MMC) and 5-fluorouracil (5-FU) or intra-arterial hepatic chemoembolization using heated albumin microspheres containing MMC with an average diameter 45 +/- 8 micron. Nineteen of the 32 patients received the MMC microsphere treatment and another 13 received the conventional infusion treatment, lasting for 3.4 months. The administered doses of MMC microspheres were 11.7 +/- 11.1 mg as MMC in the 12 with metastatic cancer and 6.9 +/- 2.1 mg as MMC in the 7 with hepatocellular cancer (HCC). On the contrary, the 13 patients who underwent conventional infusion had average doses of MMC 34.5 +/- 17.3 mg and of 5-FU 13.4 +/- 7.7 g, over 3.4 months. An objective tumor response was obtained in 13/19 (68.4%) under MMC microsphere chemoembolization, compared to 6/13 (46.2%) under the conventional infusion. The average level of CEA in the 12 with metastatic cancer, who underwent MMC microsphere therapy, dropped from 57.7 ng/ml to 16.5 ng/ml, while that in the 10 patients on conventional infusion dropped from 24.0 ng/ml to 17.4 ng/ml; that of alpha-fetoprotein dropped in all 7 with HCC on MMC microsphere chemoembolization, compared to a fall in 1/3 on conventional infusion. With the MMC microsphere treatment, 5 patients from colorectal cancer lived for 15.6 +/- 7.6 months, 2 are alive with a long life expectancy; and 7 patients from gastric or pancreatic cancer lived for only 9.3 +/- 3.3 months. In case of conventional infusion, 6 patients from colorectal cancer survived for 8.6 +/- 3.2 months; and 4 patients from gastric or gallbladder cancer survived for 6.0 +/- 1.0 months. The MMC microsphere treatment is superior at P = 0.059 in survival duration to the conventional infusion treatment. However, much the same survival occurred in 7 on MMC microsphere chemoembolization and 3 on continuous infusion.     

A comparison between hepatic artery ligation and portal 5-Fu infusion versus 5-Fu intra arterial infusion for colorectal liver metastases.

AIM: A prospective randomized study was executed comparing two regimens of regional therapy for liver metastases from colorectal cancer. METHODS: Eighteen patients were allocated to hepatic artery occlusion for 16 h followed by intraportal 5-fluorouracil (5-Fu) infusion (1000 mg/m(2)) for 5 days every sixth week (HAO). Twenty-one patients received intra-arterial 5-Fu infusion+Leucovorin (100 mg) i.v. for 2 days every second week (HAI). The follow up every third month included CT and CEA. Thirteen patients had limited extrahepatic cancer. At tumor progression regional therapy was stopped and systemic chemotherapy or the best supportive care was administered. RESULTS: The study was discontinued after randomization of 39 patients. No significant difference in survival within patients with and without extrahepatic cancer was present. The mean survival was longer in the HAI group than for the HAO group (19 months versus 13 months, p=0.0147) (median 18 (8-37) versus 12 (2-26). PR and SD were registered in 8/18 in the HAO group and 17/21 patients in HAI group. The median time to progress was 4 (1-22) months versus 7 (1-23) months for the HAO and HAI group, respectively. CONCLUSION: Regional intraarterial infusion with 5-Fu gives significantly better survival than hepatic artery occlusion followed by portal infusion. A limited amount of extrahepatic cancer does not influence survival time. A trial comparing hepatic artery 5-FU infusion and Leucovorin versus the most effective systemic therapy is warranted.     

Evaluation of continuous intra-arterial infusion chemotherapy after hepatic resection of liver metastases in colorectal cancer

We retrospectively evaluated continuous intra-arterial infusion chemotherapy after hepatic resection for hepatic metastases of colorectal cancer. From 1982 to 1990, we treated 22 patients with continuous intra-arterial infusion chemotherapy after hepatic resection, and 43 patients with only hepatic resection. 5-FU (250 mg/day) was administered continuously through implantable reservoir immediately after hepatic resection, and continued as long as possible. The total dose of 5-FU administered was 1.75-46.0 g (mean 17.4 g). We divided the patients into three groups: the first was administered a total dose of 5-FU more than 15 g, the next with less than 15 g, and the last with only hepatic resection was not given 5-FU. The 5-FU group receiving more than 15 g showed the lowest rate of hepatic metastasis recurrence. We compared the group showing recurrence within six months after hepatic resection (early recurrent group) with the group evidencing recurrence on and after six months (late recurrent group). In the former group, extra-hepatic recurrence significantly increased, whereas in the latter group hepatic recurrence significantly increased (p less than 0.05). In the early recurrent group, moderately or poorly differentiated adenocarcinoma significantly increased (p less than 0.01). According to the pathological result of pre-operative biopsy, one should check for extra-hepatic lesion as much as possible, and choose systemic chemotherapy for the early recurrent group.     

Hepatic arterial infusion chemotherapy for unresectable liver metastasis of gastrointestinal cancers

Thirty-two patients with colorectal cancer, eleven with gastric cancer and two with pancreatic cancer were treated by hepatic arterial infusion chemotherapy from March 1988 to December 1999. A single administration of 5-FU, MMC and epirubicin (FAM group), or intermittent continuous infusion of 5-FU 500 mg/2 h (5-FU continuous group) was used for each patient once a week. Overall survival rates were not significantly different between the gastric and colorectal cancer patients. In patients with colorectal cancer, there was a significant prolongation in overall survival for the response group. With gastric cancer, however, there was no significant difference. For both of the two patients with pancreatic cancer, although they were responsive to the therapy, there was no prolongation of survival. In conclusion, intermittent continuous infusion was more effective for the patients with colorectal cancer. In patients with gastric and pancreatic cancer, hepatic intra-arterial infusion could control the progression of liver metastasis.     

Successfully treated locally advanced breast cancer by intra-arterial infusion chemotherapy: a case report]

A 40-year-old female was admitted to our hospital with a large right breast tumor that was over 15 cm in diameter. We treated this locally advanced breast cancer by intra-arterial infusion chemotherapy. Through a catheter placed in the right subclavian artery, doses of 20-30 mg of ADM were injected intermittently with MMC and 5-FU. When a total of 120 mg of ADM had been infused, leukopenia developed, but this was immediately improved by G-CSF. With this treatment, her breast tumor and lung metastases were almost completely disappeared. Thus, an intra-arterial infusion chemotherapy was considered to be an effective treatment for locally advanced breast cancer.     

Intra-arterial chemotherapy for head and neck cancer

There are historically speaking, three methods of intra-arterial infusion for head and neck cancer. Recently, daily concurrent chemoradiotherapy using new superselective intra-arterial infusion via superficial temporal arterial artery is noted. A catheter with a curved tip is inserted superselectively to the feeding artery of the tumor via the superficial temporal artery. Long-term catheterization is possible in this method. Thirty-five patients with stage III or IV oral cancer were treated. Radiotherapy (total dose:40 Gy/4 weeks) and superselective intra-arterial infusion chemotherapy using DOC (total dose: 60 mg/m2, 15 mg/m2/week) and CDDP total dose: 100 mg/m2, 5 mg/m2/day) were concurrently performed daily, followed by surgery. In 31 patients, intra-arterial infusion was successful(successful rate: 88.6%), and no major complication was observed. The clinical effects were CR in 25 patients(80.6%), and pathological effects of resected tumor after surgery were pathological CR in 28 (90.3%). This method promises to be new strategy of choice for the treatment of head and neck cancer.     

Evaluation of intra-arterial infusion chemotherapy for liver metastasis from colorectal cancer

We evaluated the effect of intra-arterial infusion chemotherapy for liver metastasis from colorectal cancer. Of 405 patients undergoing colectomy in our department from July 1993 to February 2002, 38 had liver metastasis. We performed catheterization intra-operatively or postoperatively, and intra-arterial infusion chemotherapy was given for liver metastasis from colorectal cancer. Thirty-eight patients were treated with four different arterial infusion courses that mainly consisted of 5-FU. The 5-year survival rate was 8%. Maximal survival period was 68 months, and mean survival was 22 months. The effective rate was 20% Intra-arterial infusion chemotherapy was a useful treatment for liver metastasis from colorectal cancer. Resection of the liver metastasis was the first choice for operative liver metastases from colorectal cancer, and we performed intra-arterial infusion chemotherapy for patients postoperatively or patients with non-operative liver metastasis.