Antitumor effect of liposome-entrapped adriamycin administered via the portal vein

We examined the distribution in tissues and antitumor effect of freeze-dried liposome-entrapped adriamycin (Lipo-ADM) administered via the portal vein to rabbits bearing VX2 tumors. Liposomes composed of egg phosphatidylcholine (cholesterol 50 mol%) were used as drug carriers. The liver concentration of ADM increased after delivery and cardiac uptake decreased compared with free drug treatment. The in vivo antitumor effect of Lipo-ADM was determined in rabbits inoculated with VX2 tumor. Repeated injections of free ADM via the portal vein prolonged the life span of tumor-bearing rabbits. The life span was further prolonged by Lipo-ADM treatment compared with the control group and the free ADM group. Histological examination revealed that the damage to the liver caused by Lipo-ADM administered via the portal vein did not differ from that observed in animals treated with free ADM. These results indicate that portal vein administration of Lipo-ADM may be more effective in dealing with liver metastases than treatment with free ADM and may be therapeutically useful without toxic side effects.     

Systemic chemotherapy in inoperable or metastatic bladder cancer.

Urothelial cancer is a common malignancy. The management of patients with recurrent disease after cystectomy or initially metastatic or unresectable disease represents a therapeutic challenge. Systemic chemotherapy prolongs survival but long-term survival remains infrequent. During recent years there has been improvement due to the use of novel chemotherapeutic agents, mainly gemcitabine and the taxanes. The long-considered-standard MVAC has been challenged by combinations showing more favourable toxicity profiles and equal (gemcitabine-cisplatin) or even improved (dose-dense, G-CSF-supported MVAC) efficacy. Specific interest has also been generated in specific groups of patients (elderly patients, patients with renal function impairment or comorbidities), who are not fit for the standard cisplatin-based chemotherapy but can derive significant benefit from carboplatin- or taxane-based treatment. Retrospective analyses have enabled the identification of groups of patients with different prognoses, who possibly require different therapeutic approaches. Modern chemotherapy offers a chance of long-term survival in patients without visceral metastases, possibly in combination with definitive local treatment. Finally, the progress of targeted therapies in other neoplasms seems to be reflected in advanced bladder cancer by recent studies indicating that biological agents can be combined with modern chemotherapy. The true role of such therapies is currently being evaluated.     

Combination chemotherapy of metastatic breast cancer with vincristine adriamycin and prednisolone

Fifty patients with metastatic breast cancer were treated with a combination of vincristine, Adriamycin and prednisolone (VAP) at four weekly intervals. Response rates of 78% for soft tissue disease, 66% for parenchymal lung disease, 67% for liver disease, and 64% for pleural effusions were seen. Only 26% of patients with bone metastases showed an objective response. These figures are as good as any previously reported for chemotherapy of breast cancer.     

Prediction of outcome in metastatic breast cancer treated with adriamycin combination chemotherapy

Univariate and multivariate regression methods were used to analyze 17 potential clinical prognostic factors among 138 patients with advanced breast cancer who received Adriamycin-cyclophosphamide combination chemotherapy between 1973 and 1977 at the University of Arizona. Follow-up of patients was through September 1979, and survival data were nearly complete. Different factors varied in the relationship to outcome, but age, treatment, and response were important. Selecting the three most strongly related factors, predictive regression equations were developed, which described three types of possible outcome: 1) objective response (age, treatment, and liver involvement), 2) freedom from relapse (age, lung involvement, and response), and 3) survival (age, the number of involved sites [less than or equal to 2 or > 2], and treatment). Since use of the regression equations is cumbersome for clinical practice, three simplified tables were constructed to readily predict response, duration of response, and survival before the initiation of treatment.     

原发性肝癌合并门脉癌栓的治疗

目的 观察６１例原发性肝癌合并门脉癌栓患者的治疗效果。方法 Ａ组（３６例）行肝动脉化疗栓塞（ＴＡＣＥ）治疗,Ｂ组（２５例）行ＴＡＣＥ结合外放射综合治疗,两组一般临床资料无显著差异（Ｐ〉０．０５）。结果 Ａ组１、２年生存率分别为２２．３％、４．５％,平均生存期７．５个月;Ｂ组１、２、３年生存率分别为３９．２％、２１．２％、１７．２％,平均生存期１３．５个月,两组差异有显著性（Ｐ〈０．０５）。结论 对     

多西他赛联合FP方案微泵节拍化疗治疗晚期胃癌的临床应用

目的探讨多西他赛联合FP方案微泵节拍化疗治疗不能手术的晚期胃癌患者的临床疗效和不良反应。方法选择36例不能手术治疗的晚期胃癌患者,以5-氟尿嘧啶0.375g/d持续静脉输注21d,顺铂10mg/d持续输注5d,休息2d,每周重复,共2次;国产多西他赛20mg持续静脉输注1h,第1、4、8、11、15、18d给药,用药3周后休息1周,28d为1个周期,每治疗2个周期后评价疗效。结果 36例患者总有效率(RR)为55.6%(20/36),疾病控制率(DCR)为97.2%(35/36),1年生存率为88.9%(32/36),18个月生存率为61.1%(22/36),2年生存率为13.9%(5/36),生活质量明显改善,Ⅲ度不良反应少见,无Ⅳ度不良反应。结论多西他赛联合FP方案微泵节拍化疗治疗晚期胃癌具有一定疗效,毒副反应小,依从性高,可作为晚期胃癌的一种有效治疗手段。     

电化学治疗联合化疗泵植入治疗肝转移癌的临床研究

目的　电化学治疗 (ECT)联合门静脉系局部区域化疗治疗肝转移癌的疗效评估。方法　 4 0例肝转移癌患者随机分成两组 ,A组门静脉系植入化疗泵化疗配合ECT治疗 ,B组单纯门静脉系植入化疗泵化疗。结果　A组 7例患者完全缓解 (CR) ,7例部分缓解 (PR) ,有效率 (CR +PR) 70 %。B组CR患者 0例 ,PR患者 5例 ,有效率 2 5 %。两组CEA、CA199指标及血清免疫球蛋白效价的变化有明显差异。结论　ECT联合门静脉系区域化疗治疗肝转移癌 ,提高了缓解率和近期生存率。     

Clinical evaluation of weekly hepatic arterial infusion chemotherapy in patients with unresectable metastatic liver cancer

Twenty-five cases with unresectable metastatic liver cancers were experienced in our hospital over the past five years who underwent weekly 24-hour continuous hepatic arterial infusion chemotherapy using 5-FU and CBDCA. The response rate was 20%, the median survival was 23 months, and the one/two year overall survival rates averaged 81.3/45.5%. In 77% of patients, this therapy prevented death from hepatic metastases. Moreover, since adverse effects were limited compared with bolus infusion, weekly 24-hour continuous hepatic arterial infusion chemotherapy was thought to be a favorable method.     

Visualizing portal vein metastatic trafficking to the liver with green fluorescent protein-expressing tumor cells

Cell migration or trafficking is an integral aspect of cancer metastasis and is a target for development of novel antimetastatic therapy. Tumor cell trafficking has been a poorly understood phenomenon due to the inability to visualize the process. In this study, we visualized the trafficking of metastatic cells targeting the liver via the portal vein using green fluorescent protein (GFP)-expressing cancer cells. Within 72 h after transplantation of tumor cells, on the ascending colon in nude mice, metastasis was visualized ex vivo on a single-cell basis around the portal vein by GFP imaging. At this early time-point, a few cells were visualized trafficking to the liver via the portal vein. By post-implantation day-5, the caudate lobe of the liver was involved with trafficking metastatic cells. Metastasis around the portal vein increased more rapidly than those in other areas of the liver. By day-7 post-implantation, the right lateral lobe of the liver was involved with trafficking metastatic cells. By days-9 and -11, metastasis increased rapidly around the portal vein and then spread to other areas of the liver. These experiments demonstrate the critical role of the portal vein in metastasis to the liver.     

Regional chemotherapy of colorectal cancer metastatic to the liver

Ninety-three patients with biopsy-proven colorectal cancer metastatic to the liver were treated with hepatic arterial infusion of 5-fluorodeoxyuridine (FUDR). There were 52 men and 41 women (median age, 60 years). Forty-two patients (45%) had failed prior systemic chemotherapy. Catheters were operatively placed and multiple catheters were used if dictated by hepatic arterial anatomy in order to obtain perfusion of the entire liver. The drug was delivered by a totally implanted INFUSAID model 400 pump and patients received cyclic therapy consisting of 2 weeks of 0.3 mg/kg/d FUDR alternating with 2 weeks of saline. Patients with extrahepatic tumor or patients whose hepatic tumor failed to respond to FUDR were given a 30 minute intraarterial infusion of mitomycin C, 15 mg/m2, every 6 to 8 weeks in addition to FUDR. Fifty of the 93 evaluable patients presented with metastatic tumor confined to the liver. Of these 50 patients, 83% demonstrated a significant reduction in tumor size with a median duration of response of 13 months and a median survival of 25 months from diagnosis of liver metastases. Twenty-four of these 50 patients remain alive. Forty-three patients presented with extrahepatic metastases in addition to their liver tumor, and 74% had a response with a median duration of 6 months and a median survival of 14 months. Only six patients of those presenting with extrahepatic tumor remain alive. None of the 93 patients died solely of uncontrolled liver tumor, and only 9 died as a result of uncontrolled liver metastases and disseminated extrahepatic tumor. The duration of survival for both groups was determined by the uncontrolled progression of extrahepatic tumor. In patients with metastatic colorectal cancer involving only the liver, hepatic arterial FUDR alone and with the addition of mitomycin C provided excellent control of hepatic tumor. Survival appeared to be prolonged in this uncontrolled study.     

超声引导下经皮肝穿刺门静脉插管治疗肝癌

目的:探讨B超引导下经皮肝穿刺门静脉插管的可行性、操作技术及其在肝癌介入治疗中的应用价值。方法:在超声引导下,选用微创穿刺器械,对31例肝癌患者进行经皮肝穿刺门静脉插管及药盒系统植入。结果:31例(100%)患者经皮肝穿刺门静脉插管获得成功,未出现严重并发症。结论:采用超声引导经皮肝穿刺门静脉插管是一种可供选择的门静脉插管方法。     

ALPPS与门静脉栓塞治疗未来剩余肝脏体积不足肝癌临床疗效的Meta分析

目的:探讨联合肝脏分隔和门静脉结扎的分阶段肝切除术（associating liver partition and portal vein ligation for staged hepatectomy,ALPPS）和门静脉栓塞（portal vein embolization,PVE）两种术式治疗未来剩余肝脏（future liver remnant,FLR）体积不足肝癌的可行性、安全性和有效性。方法:通过检索PubMed、Web of Science、Embase、Cochrane、中国知网、万方、维普数据库中有关ALPPS与PVE治疗FLR不足肝癌临床疗效对比的所有文献,检索时间为数据库建库至2021年05月。采用RevMan 5.3软件对数据进行分析。结果:共纳入17篇文献,含1 145例患者。进行荟萃分析后显示:在二步手术完成率（OR=9.62,95%CI:5.35～17.28）、R0切除率（OR=2.01,95%CI:1.05～3.83）方面ALPPS组与PVE组之间的差异具有统计学意义（P<0.05）,ALPPS组可显著改善患者的二步手术完成率及R0切除率;在90天病死率、术后肝功能衰竭率、总体并发症发生率、3年生存率方面ALPPS组与PVE组之间的差异无统计学意义（P均>0.05）。结论:ALPPS相较PVE在治疗FLR不足肝癌时可显著改善患者的二步手术完成率及R0切除率,且两者有相似的围手术期疗效及肿瘤学结局。     

减量化疗肝动脉栓塞治疗肝癌合并门脉癌栓的研究

目的研究减量化疗肝动脉栓塞治疗伴有门脉癌栓原发性肝癌的安全性及疗效。方法回顾性分析172例经减量化疗肝动脉栓塞治疗的伴有门脉主干和（或）一级分支癌栓的原发性肝癌。其中合并门脉一级分支癌栓者76例,合并门脉主干（包括同时合并门脉一级分支）癌栓者96例。结果 172例肝癌的中位生存期为8.0月,1、2、3年生存率分别为39.5%、22.3%、17.0%。伴有门脉一级分支癌栓与伴有门脉主干癌栓的两组患者平均生存时间差异无统计学意义（18.2月vs 18.5月,P〉0.05）;两组1、2、3年生存率差异无统计学意义（39.1%、15.7%、13.7%vs 39.8%、29.3%、20.3%,P〉0.05）。单因素及多因素生存分析显示,肿瘤大小及AFP水平是生存时间的影响因素。172例患者共行377次介入,无消化道大出血、肝功能衰竭、肺栓塞等严重并发症。结论减量化疗肝动脉栓塞治疗伴有门脉癌栓的原发性肝癌是安全有效的。     

冷冻联合免疫疗法治疗无法手术的转移性乳腺癌

目的：研究冷冻联合DC-CIK（ dendritic cell-cytokine-induced killer）免疫疗法治疗转移性乳腺癌的疗效。方法回顾性分析2002年5月至2012年5月本院收治的120例转移性乳腺癌患者（共计222个转移灶）的临床资料,其中35例患者接受冷冻联合DC-CIK免疫疗法治疗（冷冻联合免疫疗法组）,29例患者接受冷冻联合化疗（冷冻联合化疗组）,27例患者接受冷冻治疗（冷冻治疗组）,29例患者接受化疗（化疗组）。在27例仅接受冷冻治疗的患者中,有18例患者接受单次冷冻治疗,9例患者接受多次冷冻治疗。对所有患者进行定期随访,总生存期以诊断为转移性乳腺癌时开始计算。采用单因素方差分析、Kruskal-Wallis检验和Friedman检验比较患者的一般情况。采用Kaplan-Meier法绘制生存曲线,各组患者总生存期的比较采用Log-rank检验。结果冷冻联合免疫疗法组中位生存期为83（69．5~113．0）个月,冷冻联合化疗组中位生存期为48（30．0~64．0）个月,冷冻治疗组的中位生存期为43（30．5~53．0）个月,化疗组中位生存期为27（18．0~41．0）个月,4组间差异有统计学意义（χ2=20．30, P=0．000）;其中,冷冻联合免疫疗法组总生存期显著长于冷冻联合化疗组、冷冻治疗组和化疗组（χ2=27．58,P=0．000;χ2=27．76,P=0．000;χ2=74．21, P=0．000）。在冷冻治疗组中,多次冷冻组与单次冷冻组的中位生存期分别为54（37．0~67．0）个月和35（28．0~48．5）个月,多次冷冻组总生存期显著长于单次冷冻组（χ2=6．25,P=0．012）。各组乳腺癌患者均未发生严重的术后并发症。结论冷冻联合免疫疗法能显著延长无法手术的转移性乳腺癌患者的总生存期。     

Phase I-II study of hepatic intraarterial one-shot administration of adriamycin in patients with metastatic liver cancer

For the purpose of obtaining the optimal dose of adriamycin (ADM) in hepatic intraarterial one-shot administration, phase I-II study was conducted in 14 patients with various liver cancers. The starting dose of ADM was 20 mg/m2 (4 patients) and the doses were escalated to 40 mg/m2 (5 patients), 60 mg/m2 (4 patients) and 80 mg/m2 (3 patients). One patient with salivary gland cancer showed PR for the liver metastasis. Major toxicity was leukopenia. With a dose of 40 mg/m2, 3 out of 4 patients showed nadir of WBC counts below 4,000/mm3 (2,400, 2,900, 3,100), 60 mg/m2 (1,100, 1,500, 2,200 and 2,700), and 80 mg/m2 (900, 1,200, and 1,400). Nadirs of WBC counts were observed from 9 to 15 days after the one-shot administration, and recovered above 4,000/mm3 in 1 to 3 weeks. Plasma concentrations of ADM from the peripheral vein were determined by HPLC in 12 patients, 14 courses. The curves of ADM plasma levels after 20 and 40 mg/m2 bolus injections were almost the same, and in patients treated with 60 and 80 mg/m2 the curves were also quite similar, but higher in the plasma levels, comparing with in patients with 20 and 40 mg/m2. There might be a limit of ADM tissue absorption, and above the doses 60 mg/m2, ADM might be overflowed, followed by side effects, especially leukopenia. Upon these data of venous plasma concentrations of ADM and leukopenia, the optimal dose of ADM in the hepatic intraarterial one-shot administration seemed to be 40 mg/m2.     

西妥昔单抗联合化疗治疗晚期结直肠癌的临床观察

目的：观察西妥昔单抗联合含伊立替康方案治疗国人晚期结直肠癌的近期疗效和毒副反应。方法：１４例经病理组织学检查确诊的晚期结直肠癌患者入组,为西妥昔单抗联合伊立替康单药或ＦＯＬＦＩＲＩ方案,西妥昔单抗首次给予负荷剂量４００ｍｇ／ｍ^２,而后每周维持量为２５０ｍｇ／ｍ^２。３例患者行Ｋ-ｒａｓ检测。结果：可评价病例１２例,其中ＰＲ２例,ＳＤ５例,ＲＲ１６.７％,ＤＣＲ５８.３％。１２例患者中位ＴＴＰ为９.３周。ＭＳＴ为４１.３周。２例Ｋ-ｒａｓ野生型的患者中,１例获得ＰＲ,ＴＴＰ为３２周;１例ＳＤ。１例Ｋ-ｒａｓ突变型的患者治疗２周期后ＰＤ。与西妥昔单抗相关的毒副反应为痤疮样皮疹（７８.６％）和过敏反应（１４.２％）。结论：西妥昔单抗联合化疗治疗国人晚期结直肠癌安全有效。     

进展期胃癌术中腹腔内及门静脉灌注化疗的临床价值

目的探讨进展期胃癌术中行腹腔内注入药物及门静脉灌注化疗防治腹膜腔种植转移和肝转移的临床作用.方法对280例进展期胃癌患者中147例行开腹后腹膜腔内注入化疗药物丝裂霉素(MMC)20 mg,使整个手术操作在腹腔内有化疗药物的条件下进行,并术中经横结肠系膜静脉插管行门静脉灌注MMC 20 mg,防治肝转移;另133例不行以上药物腹腔注入和门静脉灌注,进行对照观察.结果两组3年生存率分别为54.4%和40.6%(P=0.034),腹膜腔内种植转移、转移复发发生率分别为5.4%和13.5%(P=0.017),肝转移发生率分别为4.1%和12.7%(P=0.009).结论进展期胃癌术中行腹腔内化疗药物灌注,使整个手术在抗癌药物浸泡的腹腔内完成,是防止癌腹膜腔复发、种植转移的有效方法.门静脉灌注化疗防治肝转移是积极、有效的措施.