Hepatic artery ligation and portal vein infusion for liver metastases from colon cancer

Localized treatment of liver metastases from colon cancer has yielded better results than has systemic therapy. We report 19 patients with metastatic colon cancer whose bulk disease was limited to the liver, but was not amenable to surgical resection. Many of these patients had poor prognostic features: 14 had greater than 30% replacement of the liver, five had poorly differentiated tumor, and five had previously failed to respond to systemic chemotherapy. All were treated with hepatic artery ligation and portal vein infusion of chemotherapy (mitomycin C and 5-fluorouracil). Two patients (10%) died within one month postoperatively. The remaining 17 patients all improved clinically and demonstrated a marked decrease in carcinoembryonic antigen (CEA) levels. Based on follow-up physical exam, liver function tests, computed tomographic scan, and/or laparotomy, there were two complete responses, ten partial responses, four improved, and one indeterminate, for an objective response rate of 63%. Median survival of all patients was 13 months after hepatic artery ligation, and 14 months after diagnosis of liver metastases, with four patients still alive at 13+, 16+, 41+, and 61+ months after hepatic artery ligation. We believe that this form of therapy is an effective, well-tolerated alternative for patients with unresectable liver metastases.     

治疗方案对原发性肝癌预后影响的Cox回归分析

本文应用Cox回归方法研究了影响肝癌患者预后的诸因素。性别,发病年龄,肝癌发生部位等因素对生存期无明显影响。化疗、肝叶切除、分枝动脉结扎和栓塞、固有动脉结扎均可延长生存期。通过Cox回归方法研究诸治疗方案的相互作用,结果表明在14种不同治疗方案组合中有8种有效。其中非插管化疗 肝叶切除的疗效较好,优于其它7种方案,两比较P值均小于0.05。     

肝动脉插管化疗与放疗交替进行治疗原发性肝癌

 目的 观察Ⅱ期不可手术切除的原发性肝癌施行肝动脉结扎、肝动脉插管化疗及常规分割放疗的疗效。方法 全组65例为经剖腹探查判定不可手术切除的Ⅱ期肝癌，取活检并作了肝动脉结扎、肝动脉插管化疗及常规分割放疗。结果 AFP定量下降1/2以上率、1、3、5年生存率分别为67.6%、73.9%、41.5%、9.2%，PR率、二步手术切除率分别为70.8%、12.3%。结论 采用肝动脉结扎、低剂量顺铂（PDD）10mg动脉化疗6天/周与常规分割放疗5天/周交替夹心、互为协同的治疗方案能有效地减轻症状、缩小瘤体、提高手术切除率、延长生存期，且操作较为简单，易于掌握。     

Effect of infusion chemotherapy and hepatic artery ligation on normal liver: experimental study in the cat.

The effects of arterial infusion with chemotherapy alone or in combination with hepatic artery ligation on the normal liver of the cat were studied. Early in the course of treatment cats receiving chemotherapy infusion only appeared sicker than animals in other groups. Yet only 1 of 5 cats was dead at 12 weeks. In contrast, 4 of 6 animals that had hepatic artery ligation and chemotherapy infusion, and 3 of 6 that had ligation of the hepatic artery only, died during the same period of follow-up. Progressive liver damage after dearterialization accounted for the high mortality rate. Histologic examination of liver biopsies taken from animals in these latter groups revealed marked destruction of the parenchyma. These changes were more extensive in animals treated by a combination of hepatic artery ligation and chemotherapy infusion. To avoid the injurious effects of permanent interruption of the hepatic arterial flow on normal liver tissue an alternative method of hepatic dearterialization is currently under investigation.     

Tumor and liver drug uptake following hepatic artery and portal vein infusion

Anatomic dye injection studies of the blood supply of colorectal hepatic metastases suggest that tumors are supplied predominantly by the hepatic artery. Using 13N amino acids with dynamic gamma camera imaging in patients with colorectal hepatic metastases, it has been shown that hepatic artery infusion results in a significantly greater nutrient delivery to tumor compared with portal vein infusion. However, direct measurements of drug levels in tumor following hepatic artery and portal vein infusion in humans have not previously been reported. Patients with metastatic colorectal cancer confined to the liver received fluorodeoxyuridine (FUdR) through the hepatic artery or through the portal vein. All patients had previously failed systemic chemotherapy. Five patients with hepatic artery catheters were matched (by age, serum lactic dehydrogenase levels, percent hepatic replacement, and tumor size) with five patients with portal vein catheters. At operation, 3H-FUdR (1 microCi/kg) and 99mTc-macroaggregated albumin (MAA) (6 mCi) were injected into the hepatic artery or portal vein. Liver and tumor biopsies were obtained two and five minutes later. 3H and 99mTc were measured per gram tissue by scintillation and gamma counting. The mean liver levels following hepatic artery infusion (23.9 +/- 11.4 nmol/g) and portal vein infusion (18.4 +/- 14.5 nmol/g) did not differ. However, the mean tumor FUdR level following hepatic artery infusion was 12.4 +/- 12.2 nmol/g, compared with a mean tumor FUdR level following portal vein infusion of 0.8 +/- 0.7 nmol/g (P less than .01). This low level of tumor drug uptake after portal vein infusion of FUdR predicts minimal tumor response to treatment via this route. Thus, regional chemotherapy for established colorectal hepatic metastases should be administered through the hepatic artery.     

Hepatic dearterialization for nonrespectable primary and secondary tumors of the liver.

Seventeen patients with primary or secondary liver tumors were treated by dearterialization of the liver and intraportal infusion of cytotoxic drugs. In 14 cases, ligation of the main (10), right and left (1), right and middle (1), and right (2) hepatic arteries was performed. In three in whom hepatic artery ligation was considered to be contraindicated due to occlusion of the portal vein, temporary occlusion of the hepatic artery was repeated postoperatively. Only one patient died from the cause related to the ligation. Out of 14 patients who survived for more than one month ten showed an apparent regression of tumors radiologically. The mean survival period of the patients excluding those who died from other unrelated causes was 28 weeks. That of the control patients who received only chemotherapy through the hepatic artery was 13 weeks. The results were not always satisfactory, but dearterialization of the liver can be a palliative treatment for nonresectable liver tumors with a forceful combined chemotherapy.     

肝细胞癌伴门静脉癌栓不同治疗方法的比较

目的 比较肝细胞癌合并门静脉癌栓(ｔｕｍｏｒ ｔｈｒｏｍｂｉ ｉｎ ｐｏｒｔａｌ ｖｅｉｎ,ＰＶＴＴ）不同治疗方法的疗效及其意义。方法 １４７例肝细胞癌伴门静脉主干或第１分支癌栓的住院患者,按不同治疗方法分成４组：保守治疗组（Ａ组,１８例）;肝动脉结扎和（或）肝动脉插管化疗组（Ｂ组,１８例）,术后定期栓塞化疗;肝癌联同ＰＶＴＴ切除组（Ｃ组,７９例）;手术切除＋肝动脉化疗栓塞和（或）肝动脉置管或门静脉     

Serum alpha-fetoprotein levels after hepatic artery ligation and postoperative chemotherapy: correlation with clinical status in patients with hepatocellular carcinoma.

Eight patients with hepatocellular carcinoma and positive serum alpha-fetoprotein (AFP) levels were treated by hepatic artery legation and postoperative chemotherapy. Three patterns of clinical response were discerned. First, a marked decrease in AFP levels was found in five patients following the treatment. Three of these patients are alive, all with lowered or normal serum AFP levels at 20, 22, and 60 weeks after operation. Second, two patients displayed only a transient decrease in AFP levels followed by a gradual increase. Third, there was a continuous increase in AFP levels in one patient who showed no clinical improvement. The serum AFP levels in each case appeared to correlate with the prognosis of these patients. Thus, serial measurements of AFP levels may provide an index to assess the clinical result of hepatic artery ligation in patients affected with hepatoma.     

ALTERNATING CHEMOTHERAPY AND FRACTIONATED RADIOTHERAPY AS A MODALITY FOR THE TREATMENT OF PRIMARY LIVER CANCER

ＡＬＴＥＲＮＡＴＩＮＧＣＨＥＭＯＴＨＥＲＡＰＹＡＮＤＦＲＡＣＴＩＯＮＡＴＥＤＲＡＤＩＯＴＨＥＲＡＰＹＡＳＡＭＯＤＡＬＩＴＹＦＯＲＴＨＥＴＲＥＡＴＭＥＮＴＯＦＰＲＩＭＡＲＹＬＩＶＥＲＣＡＮＣＥＲＬｕＪｉｚｈｅｎ陆继珍ＬｉＢｉｎｇｘｉｎ李炳鑫ＬｉｕＫａｎ...     

术中肝动脉合并门静脉插管化疗预防肝癌手术后复发

目的 :研究原发性肝癌根治性切除以后肝动脉和门静脉插管皮下埋置药物泵预防肝癌肝内复发的效果。方法 :回顾性研究 5 4例根治性切除肝癌术后的患者 ,其中切除肿瘤后肝动脉和门静脉插管的患者为 3 1例 ,未做插管的 2 3例。随访 2～ 3年 ,对结果进行比较。结果 :插管组 1、2年以及 3年的复发率均低于未插管组。结论 :原发性肝癌根治性切除手术合并肝动脉和门静脉插管皮下埋置药物泵是预防肝癌复发的有效方法     

碘化油阿霉素肝动脉及门静脉支分期栓塞治疗原发性肝癌

Despite recent advances in hepatic surgery, management of unresectable carcinoma of the liver is still a challenging problem. From September 1988 through March 1989, 10 primary liver cancer patients were treated by hepatic artery embolization (HAE) using lipiodol-adriamycin with or without hepatic artery ligation (HAL). One of them received HAE twice in seven weeks. In two of these patients, following right HAE and HAL, right portal vein embolization (PVE) by catheterization via the ileac vein was performed. Transcatheter portal vein embolization via the ileac vein was simple, easy and safe even it was impossible to expose the hepatic hilum. All patients are alive from 7 to 12 months after operation except one who died of hepatic failure after having survived for 54 days. There was marked alleviation of symptoms and tumor shrinkage was observed in 9 out of 10 patients. HAE and PVE using lipiodol-adriamycin may have the potential of improving the therapeutic effect in patients with hepatocellular carcinoma.     

Conversion of surgically verified unresectable to resectable hepatocellular carcinoma

During the period 1978–1987, 255 patients with pathologically proven hepatocellular carcinoma (HCC) were determined by laparotomy to be unresectable, 155 (60.8%) out of them had their tumor mainly confined in right or left lobe and considered to be potentially resectable if remarkable tumor shrinkage appears after treatment. Second look operation was performed in 26 (16.8%) out of the 155 patients after marked reduction of tumor size, resection was done in all of these 26 patients. Triple or quadruple combination treatment with hepatic artery ligation (HAL), hepatic artery infusion (HAI) with chemotherapy, radiotherapy using linear accelerator, and radioimmunotherapy using 131-I antihuman HCC ferritin antibody yielded the highest conversion rate (29.8%, 14/47) as compared to double combination treatment with HAL+HAI, or cryosurgery+HAL (16.9%, 12/71) and single treatment with HAL or HAI or HAE (embolization) (0%, 0/37). The median tumor size of these 26 patients was reduced from 9.5 cm to 5.0 cm after combination treatment. The median interval between the first laparotomy and the subsequent resection was 5.0 (2–16) months. The survival rates calculated by life table method were: 1-year 86.5%, 2-year 74.3% and 3-year 74.3%. Nine cases have survival more than 3 years. Thus, multimodality combination treatment with subsequent resection might prolong survival significantly for some patients with unresectable HCC particularly confined in right lobe of a cirrhotic liver.     

经肝动脉介入治疗肝转移瘤的疗效影响因素

目的探讨影响经肝动脉介入治疗肝转移瘤的疗效的因素。方法115例肝转移瘤患者共经肝动脉介入治疗274次,化疗药物依原发肿瘤组织类型确定,肿瘤血供丰富者行栓塞治疗,栓塞剂采用超液化碘油和（或）明胶海绵,对可能影响经肝动脉介入治疗疗效的因素行COX回归多因素分析。结果COX回归多因素分析结果显示：肝转移瘤单发或多发、经肝动脉介入治疗前是否有其他部位转移、肿瘤血供状况、介入治疗后是否行辅助化疗、原发肿瘤的来源与肝转移瘤介入治疗的累积生存率关系非常密切,差异有统计学意义（P〈0．05）。结论肿瘤单发、富血供、无其他部位转移、经肝动脉介入治疗后行辅助化疗、原发肿瘤的来源是影响介入治疗疗效的主要因素。     

Starch microsphere-induced arterial flow redistribution after occlusion of replaced hepatic arteries in patients with liver metastases

In four patients with major anomalies of the hepatic artery undergoing intra-arterial chemotherapy, aberrant lobar vessels were ligated and catheters were inserted into the contralateral artery. Catheter perfusion scans performed early after ligation with 99mTc-macroaggregated albumin (MAA) showed a defective perfusion of the lobe supplied by the occluded artery (0.43, 0.23, 0.11, and 0.28, respectively, as compared to the contralateral lobe). Further MAA scans performed after catheter infusion of 90,000,000 parts of degradable starch microspheres (DSM) showed a near normal perfusion of the ischemic lobe (0.91, 0.96, 0.87, and 0.98). On the contrary, simple MAA scans performed in the first two patients 114 and 135 days after ligation showed a still defective arterial perfusion of the ischemic lobe (0.60, and 0.24). The DSM-induced redistribution of flow towards ischemic portions of the liver suggests a possible new role of DSM in regional treatment of liver tumors in cases with either occlusion of aberrant vessels or "hypovascular" tumors.     

Hepatic artery ligation with and without portal infusion of 5-FU. A randomized study in patients with unresectable liver metastases from colorectal carcinoma. The E.O.R.T.C. Gastrointestinal Cancer Cooperative Group (G.I. Group)

The aim of this multicentric prospective randomized clinical trial was to study the efficacy of hepatic artery ligation (HAL) with and without portal infusion (PI) of 5-FU in patients with liver metastasis of colorectal origin. Seventy-four patients were randomized. Sixty-seven were fully evaluable. Thirty-five patients were eligible in the HAL + PI of 5-FU group and 32 in the HAL alone group. The 5-FU infusion had to be discontinued for technical reasons in 13 patients. Complications of HAL were relatively high, including four hepatic failures (WHO grading greater than 2). Side effects of chemotherapy were limited. Five patients out of 30 had a partial response (WHO criteria) and one patient had a complete response in the group treated by HAL and PI of 5-FU. Only one patient had a partial response in the HAL alone group. Median survival for both groups was 12 months. Median time to progression for both groups was 6 months. This study did not show any advantage of delivery using the portal route in addition to hepatic artery ligation in terms of progression nor in survival of patients.     

Unilateral pulmonary artery occlusion inhibits growth of metastatic sarcoma in the rat lung

Tumors depend on their blood supply for growth. The blood supply to metastatic neoplasia of lung is usually from the pulmonary circulation or both the pulmonary and systemic circulation. The antineoplastic effect of pulmonary artery occlusion was investigated in a rat model of methylcholanthrene-induced metastatic pulmonary sarcoma. Left pulmonary artery ligation was performed on day 7 after tumor inoculation, and animals were sacrificed on day 14. The tumor burden of the left lung decreased 44% when compared with the control group. The survival of non-tumor-bearing rats undergoing left pulmonary artery ligation for 24 hours followed by right pneumonectomy after 2 weeks was also studied. No significant lung damage after a period of left pulmonary artery ligation was seen, as evidenced by both survival after contralateral right pneumonectomy and histology. Balloon occlusion of pulmonary artery, together with regional chemotherapy for patients with lung metastases, may warrant investigation. © 1994 Wiley-Liss, Inc.     

Increased adriamycin levels in hepatic implants of rabbit Vx-2 carcinoma from regional infusion

Regional infusion chemotherapy for the treatment of primary or secondary hepatic cancer should allow delivery of a higher drug concentration to the tumor with decreased systemic exposure when compared with systemic therapy. Fifteen rabbits, each implanted with two hepatic Vx-2 tumors, were treated with infusion of Adriamycin (3 mg/kg and 7.5 muCi of [14C]Adriamycin) through the hepatic artery (n = 5), portal vein (n = 5), and a systemic vein (n = 5) at 20 mg/min. 99Tc-labeled macroaggregated albumin flow images documented specific hepatic perfusion in selected rabbits using this technique. Thirty min after infusion the animals were sacrificed, and multiple specimens of liver, tumor, and heart were taken for liquid scintillation counting and high-performance liquid chromatography. The 14C label remained associated with Adriamycin and metabolites. After systemic infusion 11.5 nmol/g of Adriamycin were found in tumor, and 32.4 nmol/g were found in liver. Infusion of Adriamycin through the hepatic artery produced drug levels of 34.3 nmol/g of tumor and 48.4 nmol/g of liver, while infusion through the portal vein produced drug levels of 6.5 nmol/g of tumor and 54.4 nmol/g of liver. The drug concentration in tumor was significantly higher after hepatic artery infusion compared with systemic (P less than 0.05) or portal vein (P less than 0.01) infusion. The tumor/liver ratio of [14C]Adriamycin tissue levels after hepatic artery infusion was greater than that measured after systemic vein treatment (no overlap of the 90% confidence intervals). Systemic infusion of Adriamycin produced a higher level of Adriamycin in the heart (13.6 nmol/g) than did hepatic artery (10.9 nmol/g) or portal vein (8.9 nmol/g) infusion. Hepatic artery infusion achieved the highest tumor Adriamycin level compared with systemic vein and portal vein infusion. The results suggest that these tumor implants are supplied primarily by the hepatic artery, that clearance of Adriamycin is efficient after regional infusion, and that systemic toxicity may be reduced using intraarterial infusion of Adriamycin for hepatic tumors.     

左锁骨下动脉双管同时置入治疗直肠癌肝转移疗效观察

目的探讨治疗直肠癌伴肝转移的新方法。方法对11例直肠癌伴肝转移患者行左锁骨下动脉双管置入,行规律动脉化疗。结果11例患者中,8例存活2年以上,2年生存率为72.7%,效果令人满意。结论动脉双管置入对于直肠癌伴有肝转移者疗效明确。     

Prognostic variables in patients with hepatic metastases from colorectal cancer. Importance of medical assessment of liver involvement

Variation in response rates to chemotherapy and survival in patients with hepatic metastases from colorectal carcinoma may be due to patient selection factors. The prognostic importance of 13 factors were analyzed in 112 patients with only hepatic metastases, who were eligible for hepatic artery infusional chemotherapy. When individually analyzed, six factors were found to significantly (less than 0.001) affect survival: the percentage of tumor involvement of the liver, assessed medically or surgically; initial serum albumin and lactic dehydrogenase; initial Karnofsky performance status; and weight loss. Patients with less than or equal to 30% liver involvement had a median survival of 24 months versus 10 months if they had greater than 30% involvement. There was a highly significant agreement between medical and surgical assessment of liver involvement (P = 0.0001). When the variables affecting survival were studied together by multivariable analyses, the most important factor was the medical assessment of liver involvement accomplished by evaluation of radionuclide liver scan and CTT scans. The next two most important factors in the model were the ability of the patient to obtain a tumor response and the presence or absence of weight loss. Only one factor helped predict response to chemotherapy, the type of perfusion seen on a 99Technetium-macroaggregated albumin (MAA) arterial flow scan. Forty-five percent of patients with good perfusion had a partial response while 13% of patients with poor perfusion had a tumor response (P = 0.006). We recommend that future studies, dealing with patients who have hepatic metastases from colorectal carcinoma and are eligible for hepatic arterial infusion, document and stratify for the following factors: the percentage of liver involvement, the presence or absence of weight loss, and the type of perfusion seen on MAA scans.