Complications related to hepatic arterial infusion chemotherapy for liver metastasis from colorectal cancer

We evaluated the complications of hepatic arterial infusion (HAI) chemotherapy in patients (pts) with hepatic metastasis from colorectal cancer. The subjects consisted of 61 pts with hepatic metastasis from colorectal cancer, who were treated by combined chemotherapy with 5-FU and CDDP weekly or continuously. Indwelling route of catheter: 30 via gastroduodenal artery (GDA) at the time of laparotomy ('LP'), 21 via femoral artery (FA) and catheter tip in PHA ('PHA'), 10 via FA and catheter tip is inserted with steel coil into the GDA ('GDA-coil'). Complications resulting in interruption of therapy occurred in 19 pts (31%), and the 'GDA-coil' method had a lower rate of complication than others. There was no difference in the incidence rate of complications between the two chemotherapy regimens. The complications of this therapy were: 8 (13%) cases of hepatic arterial occlusion, 3 (5%) cases of duodenal ulcer, 4 (7%) cases of catheter tip dislocation, 2 (3%) cases of catheter tip dislocation to the duodenal bulb, and 1 (2%) case of liver abscess. Hepatic arterial occlusion occurred frequently in LP. Up to 67% of patients with duodenal ulcer had hepatic arterial occlusion at the same time. All pts with catheter tip dislocation were 'PHA', and all pts with catheter tip dislocation to the duodenal bulb were 'LP'. In conclusion: 1. The best indwelling route for the catheter is by the 'GDA-coil' method. 2. To diagnose complications soon, regular CTA or DSA is necessary.     

Complications related to arterial infusion chemotherapy in patients with hepatic metastasis from colorectal cancer

Complications of hepatic arterial infusion chemotherapy were analyzed in 30 cases with hepatic metastasis from colorectal cancer from July 1993 to February 2000 in our department. Thirty patients were treated with three kinds of arterial infusion course that mainly consisted of 5-FU. Complications resulting in interruption of therapy occurred in 10 patients (33%), and there was no difference in the incidence rate of complications among the three chemotherapy regimens. The complications with our therapy were hepatic arterial occlusion in two patients, catheter tip dislocation in four patients, fistulus between the hepatic artery and common bile duct in two patients, and fistulus between the hepatic artery and duodenal bulb in two patients. Four patients who had severe complications with fistulus all underwent hepatectomy, especially right hepatic lobectomy in two cases. Sixty percent of our patients had complications after hepatectomy, so regular GIF and DSA are necessary to prevent severe complications after hepatectomy.     

Effect of hepatic arterial infusion chemotherapy for liver metastasis from gastric cancer

We performed hepatic arterial infusion (HAI) chemotherapy for 4 patients with advanced gastric cancer who had undergone curative resection except for liver metastasis. The main antineoplastic drugs were 5-fluorouracil (5-FU), mitomycin C (MMC) and cisplatin (CDDP). A catheter was inserted into the hepatic artery by interventional radiological techniques in 3 patients and operatively in 1 patient. The response rate for 4 patients was 75% (CR2, PR1, PD1). The adverse events were Grade 3/4 nausea and/or vomiting in 2 cases. The HAI chemotherapy was effective and useful for patients with advanced gastric cancer who had no unresectable lesions except for liver metastasis.     

Usefulness of hepatic arterial infusion chemotherapy for liver metastasis in gastric cancer]

We have performed intra-hepatic arterial chemotherapy for 9 patients with liver metastasis arising from gastric cancer. We mainly used 5-FU and CDDP as antineoplastic drugs. RESULTS: The median survival after gastrectomy was 600 days. Of 9 cases, 2 showed CR, 4 PR, 2 NC, 1 PD. The response rate was 67%. The 9 cases were classified into 2 groups. One group, the short-term survival group, concised of 5 patients that had no more than 2 years survival and the other, the long-term survival group, consisted 4 patients that had more than 2 years survival. We compared these 2 groups and found no difference in the primary lesions between the 2 groups. The patients in the long-term survival group had fewer and smaller metastatic lesions in the liver than the patients of the short-term survival group. The patients in the long-term survival group had no unresectable lesions except liver metastasis when gastrectomy was performed. However, 2 patients in the short term survival group had unresectable lymphatic involvement at the time gastrectomy was performed. Of 9 patients, 6 died from the extrahepatic lesion. CONCLUSION: The intra-arterial chemotherapy was effective and useful for liver metastasis arising from gastric cancer. However, the majority of patients died from extrahepatic lesions. We should therefore consider the use of systemic chemotherapy with intra-arterial chemotherapy.     

Evaluation of intermittent hepatic arterial infusion chemotherapy for multiple liver metastasis of colorectal cancer

Five patients with synchronous multiple hepatic metastasis of colorectal cancer were treated with hepatic arterial infusion chemotherapy. All cases received intermittent 5-FU infusion (5-FU 250-1,000 mg/2-3 hrs/1-2 weeks) on an outpatient basis. In the evaluation of 5 cases, 3 PR and 1 NC were observed. One case administered arterial infusion for adjuvant chemotherapy has no recurrence in liver. In two patients, extra-hepatic metastases were found. In conclusion, this therapy was effective and useful for hepatic metastasis. Moreover, other forms of treatment for extra-hepatic metastasis must be used.     

Brain infarction related to hepatic arterial infusion chemotherapy]

We examined the occurrence of brain infarction with hepatic arterial infusion chemotherapy for liver cancer. One hundred and eighty-one cases of hepatic arterial infusion chemotherapy were carried out for liver cancer patients in 4 hospitals associated with Osaka University 2nd Dept. of Surgery. These included metastatic (n = 103) and primary (n = 78) liver tumors. The medication was mainly 5-FU with/without CDDP and IFN. Catheters were inserted via the left subclavian artery in 106 cases and via the femoral artery in 75 cases. Among these patients, brain infarctions occurred in seven patients. Occlusions were found in the cerebellum (n = 3), thalamus (n = 1), brain stem (n = 1) and TIA (n = 2). All these patients had catheterization from the left subclavian artery. Furthermore, 64 patients of Ikeda Municipal Hospital were examined and analyzed for brain infarction, in order to eliminate the difference between facilities (all patients in Ikeda Municipal Hospital were catheterized via the left subclavian artery). Many more brain infarctions occurred in metastatic liver cancer patients than in primary liver cancer patients. The hemostasis function deteriorated in primary liver cancer patients, and is thought to be involved in the brain infarction. Six of seven cases of brain infarction occurred in vertebral artery supply area. It may be that the occurrence of brain infarction was related to the flow of the blood vessels.     

A case of hepatic arterial infusion chemotherapy with docetaxel for liver metastasis from breast cancer

We experienced a case of hepatic arterial infusion chemotherapy using docetaxel for liver metastasis, which showed no response to CEF therapy, from breast cancer. A 63-year-old woman had undergone modified radical mastectomy for right breast cancer (T2aN1bM0: Stage II) in October, 1995. Six-cycle CMF therapy and toremifene citrate (40 mg/day) were administered as adjuvant therapy, but multiple recurrent tumors in liver, lung, and local site were detected in February 1997. Six-cycle CEF therapy was given for recurrent disease and there was a complete response for lung and local recurrence, but no change in liver metastasis. Chemoendocrine therapies using 5'-DFUR or CMitF in addition to TAM and fadrozole hydrochloride hydrate had developed progressive disease for liver metastasis. A catheter and port kit were operatively inserted and implanted in March 1998. Hepatic arterial infusion of docetaxel (30-40 mg/body/month, one hour administration) was repeated 4 times, once in our clinic. Leukopenia, general fatigue and fever, which were mild and did not require any treatment, appeared as side effects. This treatment reduced multiple liver metastatic sites on abdominal CT finding and was thought to be a partial response. However, the patient had multiple brain metastasis and died on August 2, 1998. While docetaxel, even by systemic administration, has a 36-77% response rate for liver metastasis, arterial infusion might have a good response and mild side effect with a lower dose than by intravenous administration.     

Rules to carry out hepatic arterial infusion chemotherapy at home for patients with liver metastasis of colorectal cancer

We analyzed the effectiveness and adverse effects of hepatic arterial infusion chemotherapy (HAI) for patients with liver metastasis of colorectal cancer in order to clarify the rules of HAI. We provided HAI to 72 patients after hepatic resection and to 119 patients with unresectable liver metastases. The preventive effect on hepatic recurrence was recognized in the group administered more than 15 g of 5-FU (total dose). The response rate of patients with unresectable metastases was 60.3%. Adverse effects were observed in 65.8% of the patients. It is important to establish a follow-up system in each hospital to treat the patients as soon as possible when patients develop an adverse reaction.     

Evaluation of hepatic artery infusion chemotherapy for liver metastasis of colorectal cancer using a side-hole catheter

In our department forty cases of hepatic artery infusion chemotherapy using a side-hole catheter were analyzed with liver metastasis of colorectal cancer from December 2000 to December 2003. This easily placed catheter is able to inject the agent effectively from the side hole. The efficacy of high dose 5-FU (1,000 mg/m2/week) of hepatic artery injected chemotherapy was evaluated. The catheter was inserted from femoral or the left subclavian artery, and the side hole positioned at the base of proper hepatic artery or common hepatic artery. This method resulted in catheter trouble only 18% of the time. As for arterial infusion chemotherapy, system management and an evaluation of the drug distribution is essential. The one-year survival rate was 71.9%, the 50% survival time was 23.4 months, and the response rate was 71%. In conclusion, this therapy was effective and useful for hepatic metastasis.     

Alternating hepatic arterial infusion and systemic chemotherapy for stage IV colorectal cancer with synchronous liver metastasis

Among 41 patients with synchronous liver metastases of colorectal cancer, 15 patients underwent synchronous resection of their liver metastases and achieved a median survival time (MST) of 1,441 days (versus 748 days for the 26 patients without resection, p=0.038), a median relapse-free survival time of 652 days (MST not reached), and a recurrence rate in the residual liver of 20% (3/15 patients). The alternating hepatic arterial infusion and systemic chemotherapy showed partial response (PR) in 6 cases, stable disease (SD) in 8 cases, and progressive disease (PD) in 1 case (n=15/26). They had an objective response rate of 40% (6/15), tumor control rate (>/= SD) of 93.3% (14/15), one-year progression-free survival rate of 35.7%, 50% time to progression of 270 days, one-year survival rate of 76.2%, and two-year survival rate of 50.8% (MST not reached). Grade 3 leucopenia was observed in 2/15 patients (13.3%). These results suggest that the present alternating therapy may become a standard regimen for patients in whom synchronous resection of liver metastases is impossible and patients who have stage IV colorectal cancer with a risk of recurrence in the remnant liver and/or at extrahepatic sites such as the lungs.     

Arterial infusion chemotherapy for advanced gallbladder cancer and liver metastasis

Ten patients with advanced gallbladder cancer were treated by arterial infusion chemotherapy. Seven patients had unresected tumors, and three had liver metastasis after resection of primary tumor. The infusion catheter-port system was implanted via the femoral artery. 5-fluorouracil, mitomycin C and epirubicin were administered using implantable port. The response rate was 50% and the median survival time was 192 days. In one patient with good PR, a primary tumor was resected, and he survived for 2 years 7 months without recurrence. No severe side effect was found. Systemic chemotherapy using gemcitabine is well accepted, however arterial infusion chemotherapy will be one of the options when systemic chemotherapy is fails.     

肝动脉灌注联合静脉化疗预防大肠癌术后肝转移的临床研究

目的观察肝动脉灌注联合静脉化疗预防大肠癌术后肝转移癌的疗效及毒副反应。方法治疗组28例大肠癌病人，术后3wk行肝动脉灌注联合静脉化疗6个周期，对照组28例则仅予以静脉化疗6个周期，所有病例术前、术后、化疗前后均行影像学检查以评价治疗效果，随访44mo，评价肝转移及毒副反应。结果治疗组肝转移率为：7．1％（2／28），对照组为：25．0％（7／28），但经统计学处理P〉0．05，两组之间无显著性差异，两组均无发生因化疗引起的造血系统、肝、肾功能的损害。无化疗相关的死亡病人。结论肝动脉灌注联合静脉化疗时可有效减少大肠痛术后的肝转移的发生，安全有效。     

A case of spinal infarction related to hepatic arterial infusion chemotherapy

A 65-year-old male underwent iliocecal excision and hepatic posterior segmentectomy for cecum cancer and synchronous liver hepatic metastasis in September and October 2001, respectively. A reservoir was implanted by the GDA-coil method from the right femoral artery in November, and WHF (5-FU 1,000 mg/m2) was administered 8 times. Because of the remnant liver recurrence, WHF was restarted in April 2002. Left leg paralysis appeared suddenly after the 3rd administration. Heparin and urokinase were administrated continuously after hospitalization. Also, liver function tests showed a worsening condition. The bile duct necrosis in the liver was examined with abdominal CT scan. The anti-coagulation therapy was changed to an oral drug on the 7th day after hospitalization. The liver function tests normalized gradually. Although the rehabilitation for leg paralysis performed during hospitalization was continued after discharge from the hospital, the patient is unable to walk and uses a wheelchair. Hepatic arterial infusion chemotherapy is considered safe for blood and non-blood toxicity compared with systemic chemotherapy. However, there are also complications as in this case, where QOL is reduced remarkably, and caution is required.     

Hepatectomy and intraarterial infusion chemotherapy for liver metastasis from colorectal cancer

Hepatectomy and intraarterial chemotherapy for liver metastasis from colorectal cancer have been performed in our department. Intraarterial infusion chemotherapy has also been performed for unresectable liver metastasis. One hundred twenty-seven cases of liver metastasis from colorectal cancer were studied. The cases were divided into groups according to radicability of the original colorectal cancer, whether or not hepatectomy was performed, and whether or not they received intraarterial chemotherapy. Group I is cur C of origin. Group II is cur A or B without hepatectomy. Group III is cur A or B with hepatectomy. Each group was divided into a group without intraarterial chemotherapy (A) and a group with it (B). IA 23 cases, IB 13 cases, IIA 14 cases, IIB 21 cases, IIIA 28 cases, and IIIB 28 cases. The survival rate of group III was better than that of group II. The survival rate of group II was better than that of group I. There was no significant difference in survival rates between IA and IB. The survival rate of group IIB was significantly better than that of group IIA. The survival rate of group IIIB was significantly better than that of group III A. Hepatectomy and intraarterial chemotherapy after hepatectomy for liver metastasis from colorectal cancer were effective.     

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.     

Evaluation of arterial infusion chemotherapy for liver metastasis from gastric cancer

We evaluated the effectiveness of arterial infusion chemotherapy for liver metastasis from gastric cancer. Nineteen patients (9 synchronous cases, 10 metachronous cases) were treated with hepatic arterial infusion chemotherapy (HAIC). The response rate was 26% (CR 3, PR 2, PD 14), and the median survival time was 357 days after the diagnosis of liver metastasis. The treatment was discontinued in 8 patients because of treatment associated complications and disease progression. Absence of extrahepatic lesion, response of HAIC, and hepatectomy did not improve the prognosis. The combination of systemic chemotherapy with HAIC tended to improve the prognosis. It may be necessary to reevaluate HAIC as a treatment modality for liver metastasis from gastric 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.     

Evaluation of hepatic resection following hepatic arterial infusion chemotherapy for colorectal liver metastases

We evaluated the significance of hepatectomy following hepatic arterial infusion (HAI) chemotherapy for colorectal liver metastases. The prognosis of 4 cases with initially resectable tumors was discouraging, indicating no benefit of preoperative HAI for resectable tumors. The 2- and 3-year survival of patients who underwent hepatectomy after downstaging by HAI of originally unresectable metastases were 100% and 67%, respectively, suggesting that hepatectomy combined with HAI is a promising modality for those patients. However, it seems that the control of extrahepatic disease and decision making for the timing for surgical therapy are issues requiring improvement.     

经皮植入药盒肝动脉持续灌注治疗肝转移瘤

目的 探讨5－氟脲嘧啶（5－Fu)和甲酰四氢叶酸钙（CF）经肝动脉持续性灌注治疗肝转移瘤的临床疗效。方法 对68例无外科手术指征的肝转移瘤患者（其原发病灶均已做根除术）,采取经皮经股动脉或左锁骨下动脉肝动脉内植入药盒,术后经药盒每个月连续5d持续灌注5－Fu 500mg/m^2、CF100mg/m^2及地塞米松10mg(d1-5),并选择顺铂、丝裂霉素、表阿霉素、环磷酰胺联合化疗。结果 总有效率（完全缓 部分缓解）为47．1％。肿瘤负荷＜25％者的有效为60．6％,明显高于肿瘤负荷＞25％者（34．3％,P＜0．05）。在随访的54例中,中位生存期为15．2个月,1、2年生存率分别为61．1％和35．2％。来源于胃肠癌肝转移者疗效较好,其中位生存期为17．6个月,1,2年生存率分别为68．4％和39．5％。全组无严重毒副作用或并发症,胃肠道及肝胆毒性较低。结论 经药盒肝动脉持续性灌注5－Fu、CF及地塞米松是治疗肝转移瘤的较好方法,可明显提高疗效,改善患者的生存质量。