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.     

Prehepatectomy chemotherapy using hepatic artery infusion plus systemic chemotherapy for liver metastases from colorectal cancer

The purpose of this study was to determine the efficacy of hepatic artery infusion (HAI) plus systemic chemotherapy (SYS) as the prehepatectomy chemotherapy for liver metastases from colorectal cancer. Clinicopathologic data were available for 117 patients who were treated with chemotherapy before liver surgery. Response rate of chemotherapy and frequency of liver resection after chemotherapy of patients treated with HAI/SYS (n=26; 65% and 96%, respectively) were higher than those treated with HAI alone (n=63; 41% and 70%) or SYS alone (n=28; 25% and 42%). Histological examination of adjacent nonneoplastic liver confirmed that severe sinusoidal dilatation was less frequent in HAI/SYS group than in SYS group, and moderate to severe steatosis was also less frequent in HAI/SYS group as compared to HAI group. The combination of regional HAI and systemic chemotherapy is an effective prehepatectomy regimen for the treatment of patients with aggressive liver metastases from colorectal 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.     

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.     

Regional chemotherapy: a focus on hepatic artery infusion for colorectal cancer liver metastases

Regional infusion strategies have been used as a treatment modality in multiple cancers, including ovarian, appendiceal, and colorectal cancers. Perhaps the most illustrative use of regional therapy is that of hepatic arterial infusion (HAI) for liver metastases from colorectal cancer. The administration of chemotherapy by HAI is logical and has theoretic advantages over systemic chemotherapy for the treatment of hepatic metastases from colorectal cancer. With the use of an appropriately chosen chemotherapy agent, HAI can generate an increase in hepatic tumor drug exposure as compared with intravenous delivery of the same agent. This article reviews the pharmacologic benefits of HAI therapy and the contemporary trials performed and underway.     

Therapy for metastatic colorectal cancer with hepatic artery infusion chemotherapy using a subcutaneous implanted pump

Sixty-two patients with metastatic colorectal carcinoma involving the liver were treated by hepatic intra-arterial chemotherapy using an implantable infusion pump. The 53 patients with metastases confined to the liver had a median survival (MS) of 17 months and an objective response rate of 32%. Four patients (8%) demonstrated a complete response (CR), with normal abdominal computed tomography (CT) scan results and plasma carcinoembryonic antigen (CEA) levels, and 13 patients (25%) demonstrated a partial response (PR), with at least a 50% decrease in the liver lesions by CT scan and at least a 50% decrease in CEA levels. Thirty patients (57%) had stable disease (S), and six patients (11%) had no response (NR). Nine patients with extrahepatic tumor plus hepatic metastases had an MS of only 4.9 months. None of these patients had an objective response, and only four patients had S. Quality of response was clearly associated with longevity. Forty patients treated with floxuridine (FUDR) and mitomycin (M) (F + M) showed a 20% objective response rate, while the 13 patients treated with FUDR and dichloromethotrexate (DCMTX) (F + D) attained a 69% objective response rate. Although F + D treatment appears to be superior, there may have been selection biases that make such an observation only preliminary. Twenty-six (49%) of the 53 patients developed hepatitis during infusion chemotherapy, which resolved after temporary cessation of the chemotherapy. Of the 17 patients with CR or PR, 12 patients (71%) had hepatitis, whereas only 14 (39%) of the 36 patients with S or NR had hepatitis. Eleven patients had evidence of peptic ulceration by endoscopic examination during the infusion chemotherapy. All the ulcers healed after chemotherapy was discontinued.     

Concentration of 5-FU after hepatic artery infusion chemotherapy for liver metastases of colorectal cancer

AIM: Hepatic artery infusion chemotherapy (HAI) using 5-FU is a good method of treating patients with liver metastases from colorectal cancer. We investigated the toxicity and the response in relation to the concentration of 5-FU after HAI, and examined various factors that would have an effect on the 5-FU concentration. RESULTS: The mean 5-FU concentration was 480 ng/ml. The most frequent complication of HAI was anorexia. Three of 14 patients suffered from grade 2 or 1 anorexia. The 5-FU concentration of these patients was higher (1,010, 721, 642 ng/ml) than that of the others. The response rate of HAI was 36%. The 5-FU concentration of responders tended to be lower than that of non-responders. None of the following was related to the 5-FU concentration: whether or not the gallbladder was resected, whether or not co-lateral blood flow was recognized, or the volume of the patients' liver. CONCLUSION: 5-FU concentration after HAI has some effect on anti-tumor response and gastrointestinal toxicity.     

Evaluation of the non-effective cases of irresectable multiple liver metastasis of colorectal cancer receiving hepatic arterial infusion chemotherapy

PURPOSE: Hepatic arterial infusion (HAI) chemotherapy is one of the suitable therapies for irresectable multiple liver metastasis from colorectal cancer, but in nearly half of such cases the therapy does not prove effective. Our goal is to clarify the characteristics of non-effective cases. METHODS: 84 cases with irresectable multiple liver metastasis from colorectal cancer were investigated clinicopathologically, and were divided into two groups; non-effective cases (N = 38) and effective cases (N = 46). All cases received continuous arterial infusion chemotherapy using 5-FU according to the following regimen; 5-FU (500 mg/day) was infused in the hepatic artery over 7 or 10 days for induction, and the infusion was maintained (250 mg/day) to the hepatic artery for 7 days every other week after the induction therapy. We evaluated the efficacy of HAI chemotherapy by Computed Tomography. RESULTS: There were statistically significant differences among these two groups in histological types. Rates of the histological type of non-effective cases were well (31.6%), mod (57.9%), por (7.9%), and muc (2.6%), respectively. Those of the effective cases were well (63.0%), mod (34.8%), por (0%), and muc (2.2%), respectively. In non-effective cases, 16 out of 38 cases (42.1%) had extra-hepatic metastasis. On the other hand, only 3 out of 46 cases (6.5%) had such metastasis in effective cases. CONCLUSION: There were non-well type cancers and extra-hepatic metastasis in a large number of non-effective cases. We thought that those cases were basically high-grade malignancies, so these were the limits of HAI chemotherapy for irresectable multiple liver metastasis of colorectal cancers.     

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.     

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.     

Prophylactic hepatic arterial infusion chemotherapy after resection of colorectal liver metastases using removable W-spiral catheter

The authors investigated the usefulness of W-Spiral Catheters for adjuvant hepatic arterial infusion (HAI) chemotherapy following curative resection of colorectal liver metastases. The catheter has a special shape-memory alloy in its tip, which allows preferable fixation without coils and removal of the catheter if desired. A W-spiral catheter was successfully placed in 13 out of 16 patients who had undergone curative hepatectomy. In the remaining 3 cases in which the hepatic artery was smaller in diameter, a catheter was placed using the conventional GDA coiling method. Removal of the W-Spiral Catheter was attempted in 10 of the 13 patients with a Spiral Catheter after termination of HAI chemotherapy. In all cases, the catheters were easily and uneventfully removed, and 3D-CT angiography revealed that the hepatic artery was well preserved in most cases. These findings suggest that a new approach to prophylactic HAI chemotherapy with W-Spiral Catheters and subsequent removal of the catheters is reasonable and desirable.     

Ⅲ期大肠癌术后肝动脉灌注化疗预防肝转移的临床研究

目的 观察经肝动脉灌注加静脉化疗对Ⅲ期大肠癌术后预防肝转移的作用.方法 入选21例III期大肠癌术后患者,经肝动脉灌注氟脲苷(FUDR),静脉输入草酸铂(OXA),共6个周期.随访12～48个月,观察其无病生存期(DFS)、肝转移发生率及时间、累积生存时间及安全性.结果 可评价的20例患者3年累积DFS为65.0%,肝转移发生率为5.0%,出现在术后11个月,3年累积生存率为82.9%,而且毒副作用小,基本无Ⅲ、Ⅳ度毒性.结论 对Ⅲ期大肠癌术后辅助化疗采用新的方案(FUDR/OXA)和给药途径,可以减少肝转移的发生率,延长生存期,而且安全性好.     

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.     

Evaluation of hepatic arterial infusion chemotherapy using removable W-spiral catheter

The authors analyzed the 62 patients who underwent hepatic arterial infusion (HAI) chemotherapy using W-spiral (WS) catheter. The catheter was successfully inserted into the hepatic artery without a coil fixation in 57 cases. After cessation of chemotherapy, the catheter was removed in 32 cases without difficulty, which resulted in improved patients' quality of life as well as preservation of patency of hepatic arteries. This catheter has a special shape-memory alloy in its tip, which allows preferable fixation without coils and removal of the catheter if desired. HAI using this catheter and subsequent removal of it is a reasonable strategy in the era with potent systemic chemotherapy.     

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.     

Hepatic artery infusion of chemotherapy as a treatment for hepatic metastases from colorectal cancer

Hepatic artery infusion (HAI) of chemotherapy as a treatment for hepatic metastases from colorectal cancer has become more commonly used after the introduction of the totally implantable hepatic artery pump in the early 1970s. Floxuridine (FUDR) is the generally used chemotherapy agent in the pump because of its high solubility and high extraction rates by the liver on the first pass of the chemotherapy through the hepatic circulation. HAI has been used mainly to treat unresectable liver metastases in patients who have liver metastases only. The other scenario for pump use has been as an adjuvant therapy after resection of all metastatic disease inthe liver. The rationale for HAI includes the unique dual blood supply of the liver allowing chemotherapy given into the artery and sparing the normal cells, which get their predominant blood supply from the portal vein. The details of pump design will be reviewed. Complications from HAI are specific for this therapy and will be reviewed. Treatment of unresectable liver metastases with HAI has been the subject of a number of prospective randomized studies. These will be presented, along with newer phase II studies. Three randomized studies on the usefulness of HAI after hepatic resection will be presented.     

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.     

Prognostic factors for transarterial chemoembolization combined with sustained oxaliplatin-based hepatic arterial infusion chemotherapy of colorectal cancer liver metastasis

Objective:To investigate the prognostic factors in chemorefractory colorectal cancer liver metastasis (CRCLM)patients treated by transarterial chemoembolization (TACE) and sustained hepatic arterial infusion chemotherapy (HAIC).Methods:Between 2006 and 2015,162 patients who underwent 763 TACE and HAIC in total were enrolled in this retrospective study,including 110 males and 52 females,with a median age of 60 (range,26-83) years.Prognostic factors were assessed with Log-rank test,Cox univariate and multivariate analyses.Results:The median survival time (MST) and median progression-free survival (PFS) of the 162 patients from first TACE/HAIC were 15.6 months and 5.5 months respectively.Normal serum carbohydrate antigen 19-9 (CA19-9,＜37 U/mL) (P＜0.001) and carbohydrate antigen 72-4 (CA72-4,＜6.7 U/mL) (P=0.026),combination with other local treatment (liver radiotherapy or liver radiofrequency ablation) (P=0.034) and response to TACE/HAIC (P＜0.001) were significant factors related to survival after TACE/HAIC in univariate analysis.A multivariate analysis revealed that normal serum CA19-9 (P＜0.001),response to TACF/HAIC (P＜0.001) and combination with other local treatment (P=0.001) were independent factors among them.Conclusions:Our findings indicate that serum CA19-9 ＜37 U/mL and response to TACE/HAIC are significant prognostic indicators for this combined treatment,and treated with other local treatment could reach a considerable survival benefit for CRCLM.This could be useful for making decisions regarding the treatment of CRCLM.     

结直肠癌肝转移经肝动脉栓塞及持续灌注化疗的临床疗效

背景与目的：结直肠癌肝转移患者经肝动脉介入栓塞或静脉持续滴注化疗药物,治疗效果有所提高,但尚存肿瘤局部化疗药物浓度不够高,化疗药物对肿瘤细胞的杀伤力不够强,晚期结肠直肠癌的治疗效果仍然不够好的缺陷。本文将动脉介入与持续灌注化疗药物两种方法相结合,观察结直肠癌肝转移患者经肝动脉介入栓塞或持续灌注化疗的临床疗效。方法：对26例结直肠癌肝转移患者经肝动脉介入治疗93次,单用肝动脉持续灌注化疗42次,肝动脉介入栓塞联合持续灌注化疗51次。化疗药物选用阿霉素（ADM）、顺铂（DDP）、丝裂霉素（MMC）、醛氢叶酸（CF）和5-氟尿嘧啶（5-FU）。先将ADM30mg/m^2和MMC6mg/m^2加入超液化碘油10-30ml中进行肝动脉灌注栓塞,然后留置导管进行持续动脉滴注。方案为CF200mg/m^2,d1-3,静脉滴注;DDP80mg/m^2d1,如肾功能改变则改用Vp-1660mg/m^2,d1-3,应用电动输液泵动脉滴注;5-FU2500mg/m^2,采用便携式输液泵将5-FU持续动脉滴注72h。结果：近期疗效以实体瘤疗效评价标准评价,CR1例,CR率3.85%;PR14例,PR率53.84%,总有效率为57.69%。本组0.5、1、2、3和5年生存率分别为92.31%、76.92%、38.46%、23.07%和3.85%,肝转移后中位生存期为11.5个月。全组病人出现的不良反应主要有肝功能损害、胃肠道反应和骨髓抑制,经护肝、制酸、止呕、水化和应用升白细胞药物对症治疗后可缓解。结论：经肝动脉持续灌注化疗及栓塞是治疗结直肠癌肝转移瘤的较好方法,能提高治疗效果。     

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.