Three cases of multiple liver metastases of carcinoid tumor responding to hepatic arterial infusion chemotherapy using degradable starch microspheres

We describe three patients with multiple liver metastases of carcinoid tumor who received hepatic arterial infusion chemotherapy using degradable starch microspheres (DSM). A partial response was obtained in all cases, and no side effects were observed. We believe that this chemotherapy was an effective treatment for unresectable liver metastases of carcinoid tumor.     

Indication for hepatic resection after hepatic arterial infusion chemotherapy for multiple liver metastases of colorectal cancer

The indications for hepatic resection after hepatic arterial infusion chemotherapy (HAI) for unresectable metastatic liver tumor of colorectal cancer were analyzed from the surgical outcome of hepatic resections in 23 cases of hepatic resection after HAI. The mean duration of HAI until hepatic resection was 7.4 months (5-14 months). The total dose of 5-FU was 25.7 +/- 8.0 g for a CR + PR group and 14.0 +/- 3.5 g for a NC + PD group. There was a significant difference between two groups (p < 0.01). The group in which serum CEA level normalized after HAI (the normal CEA group) included 7 patients, and the group in which serum CEA level did not normalize (the high CEA level group) had 9 patients. The total dose of 5-FU was 30.0 +/- 7.6 g in the normal CEA level group and 19.1 +/- 6.9 g in the high CEA level group. There was a significant difference between the two groups. The 3-year survival rate was 40.0% in the group with the duration of HAI for longer than 8 months (n = 10) and 0% in the group with the duration of HAI for shorter than 8 months (n = 7). The 3-year survival rate was 66.7% in the normal CEA level group (n = 3) and 0% in the high CEA level group (n = 8). The surgical outcome was better in the HAI for longer than 8 month and normal CEA groups.     

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.     

Two cases of resection of synchronous bilobar multiple liver metastases from colorectal cancer after hepatic arterial infusion chemotherapy

We report 2 cases of synchronous bilobar multiple liver metastases from colorectal cancer which are hepatectomised following a hepatic arterial infusion chemotherapy. Both cases were considered unresectable metastases before chemotherapy. Case 1: A 55-year-old male, with rectal cancer and multiple hepatic metastases, was performed a low anterior resection. Hepatic arterial infusion chemotherapy (5-FU 1 g/m2 5h qw) and systemic chemotherapy (5-FU/LV) were administered. Twelve months after the first surgery, hepatectomy was performed. Case 2: Right hemicolectomy was performed on a 66-year-old male, with cancer of the transverse colon and multiple hepatic metastases. Hepatic arterial infusion chemotherapy was administered 38 times. Thirteen months after the first surgery, hepatectomy and MCT were performed. Even among the cases of unresectable hepatic metastases from colorectal cancer, there are some in which resection is possible followed by hepatic arterial infusion chemotherapy. Re-evaluation for hepatectomy is needed for the cases where hepatic arterial infusion chemotherapy is administered.     

Efficacy of adjuvant hepatic arterial infusion chemotherapy following resection of colorectal liver metastases

PURPOSE: The aim of this study is to evaluate the effect of adjuvant hepatic arterial infusion chemotherapy (HAIC) following liver resection on the frequency of residual liver recurrence and overall survival. PATIENTS AND METHODS: During 1992 to 1997, 84 patients with liver metastasis from colorectal cancer resected curatively had undergone adjuvant HAIC. The regimen of the HAIC is 1,500 mg of 5-FU by 24-hr continuous infusion once a week for eight weeks. 37 cases in the HAIC group, including patients given more than 7 g of 5-FU, were compared with the control group. RESULT: The cumulative 5-year liver recurrence-free ratios were 72.6% in the HAIC group and 29.8% in the control group (p = 0.0005). The cumulative 5-year survival ratios were 61.4% in the HAIC group and 28.0% in the control group (p = 0.0069). Multivariate analysis revealed that more than 5 mm of surgical margin and adjuvant HAIC significantly decreased the risk of recurrences in residual liver. CONCLUSION: Adjuvant HAIC is an effective procedure to prevent recurrence in residual liver and improve the prognosis of patients with liver metastasis from colorectal cancer.     

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.     

Hepatic arterial infusion chemotherapy for colorectal liver metastases

Hepatic metastases are a frequent complication of colorectal cancer. Resection of liver metastases can result in long-term survival. However, the majority of patients have unresectable disease. Alternative methods in Japan for treating these patients are hepatic arterial infusion (HAI) chemotherapy with administration of 1,000 mg/m2 of 5-FU over 5 hours. We summarize the status of HAI chemotherapy in terms of colorectal hepatic metastases today. HAI chemotherapy produced higher response rates compared with systemic chemotherapy, but did not demonstrate elongation of survival time in many trials. Important problems remaining to be solved are the technical aspects of percutaneous implantation of intraarterial catheters connected to a subcutaneous infusion reservoir and studies of combined therapy with systemic chemotherapy. Furthermore, in order to finally determine the position of HAI for colorectal liver metastases, it is necessary to conduct a comparative study versus systemic chemotherapy, using the survival time as the primary end point.     

A case of resection of synchronous multiple liver metastases from colorectal cancer after hepatic infusion chemotherapy and systemic chemotherapy

A 70-year-old man was admitted for tranverse colon cancer with multiple liver metastases. Hepatic arterial infusion chemotherapy and systemic chemotherapy (FOLFOX 4) were conducted postoperatively. Thirteen months after the first surgery, liver metastases became resectable and hepatectomy was performed. Though multiple liver metastases were unresectable at the time of the first examination, hepatectomy was possible followed by hepatic arterial infusion chemotherapy and systemic chemotherapy.     

The efficacy and limitation of hepatic arterial infusion chemotherapy for colorectal liver metastases

We investigated the efficacy and limitation of hepatic arterial infusion (HAI) chemotherapy for colorectal liver metastases. In terms of prophylactic HAI following curative resection of liver, the 5-year disease-free survival of HAI group (12 g of 5-FU administered in 6 weeks) was 66.7%, whereas that of randomly selected control group was 20.0%. The difference was statistically significant (p = 0.045). Recurrent disease was confirmed in three cases of HAI group (one in liver) and in 8 patients of the control group (6 in liver). However, the overall survival was not significantly different between the groups. Thus, the short-term HAI of 5-FU is effective in decreasing the recurrence of disease. As for the treatment of unresectable liver metastases, some patients received HAI of 5-FU (1,000-1,500 mg/w) showed prolonged survival with partial remission of the disease. However, the 1-, 2-, and 3-year cumulative survival of HAI group (n = 27) was 69.3, 34.1 and 11.4%, respectively, against 61.3, 22.6 and 9.4%, respectively, in the transarterial embolization (TAE) group (n = 31). Therefore it is important to estimate the effect in the early phase of HAI, and aggressively continue the treatment in selected patients for whom it is suitable.     

Successful resection of multiple liver metastases from rectal cancer following initial treatment using hepatic arterial infusion chemotherapy and radiotherapy

A 69-year-old-man was referred to our hospital because of rectal cancer with multiple liver metastases. He was initially treated by hepatic arterial chemotherapy using an infusion reservoir (HACR) and radiotherapy for the rectal cancer. An abdomino-perineal resection and extended left lobectomy of the liver were performed and resulted in a reduction in size of the liver tumor. He was diagnosed as having a recurrent liver metastasis (S7) at 3 months after the operation, and was retreated by HACR in the outpatient clinic. A partial hepatectomy was reperformed at 6 months after the operation. Adjuvant hepatic arterial infusion chemotherapy (HAIC) was performed on an outpatient basis and the patient is doing well without recurrence or relapse. Preoperative arterial chemotherapy for metastatic liver tumor may be of some benefit for certain patients with far advanced colorectal carcinoma.     

Two cases of gastric cancer with multiple liver metastases responding to TS-1 with hepatic arterial infusion of CDDP following low-dose 5-FU and CDDP chemotherapy

Case 1: A 77-year-old man was revealed to have type 3 gastric cancer with synchronous liver metastases. He underwent total gastrectomy with lymphatic dissection of D1+a and tubing of the hepatic artery. After surgery, two courses of hepatic arterial infusion of low-dose 5-FU plus CDDP were performed. The patient was discharged, and TS-1 (60 mg/day) was administered from day 1 to 14 followed by 7 days rest as one course. CDDP (10 mg/ body) was infused in the hepatic artery bolus on day 8 and 15 as outpatient treatment. After 8 months, the CEA was decreased from 3,098 ng/dl to 5.4 ng/dl, hepatic metastases were decreased by 85% assessed as a partial response. Case 2: A 71-year-old man was diagnosed with multiple liver metastases 10 months after distal gastrectomy for early gastric cancer. After tubing of the hepatic artery, three courses of hepatic arterial infusion of low-dose 5-FU plus CDDP were performed. TS-1 with hepatic arterial infusion of CDDP was administered using the same regimen as an outpatient. After 4 months, hepatic metastases decreased by 73%. These cases suggest that TS-1 with hepatic arterial infusion of CDDP in an outpatient may be an effective treatment with low toxicities and no damage to QOL in gastric cancer patients with multiple liver metastases.     

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 liver metastases from colorectal cancer

After randomized studies of hepatic arterial infusion chemotherapy (HAIC) versus systemic chemotherapy for liver metastases from colorectal cancer in the 1980s, the role of HAIC has been unclear and there is still no evidence to support it as the treatment of choice. The high local control, the differences in techniques between Japan and Western countries, the difficulty of detecting pre-treatment extra-hepatic metastases and the fact that HAIC does not control extra-hepatic lesions are the most important points in considering clinical trials of HAIC. Clinical studies on the combination of HAIC using 5-FU and systemic chemotherapy using CPT-11, and then randomized trial of systemic chemotherapy with/without HAIC is required in Japan to reveal the role of HAIC in the management of liver metastases from colorectal cancer. We should understand the importance of our role in this field.     

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.     

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.     

Incidence of recurrence after hepatic resection and prophylactic hepatic arterial infusion chemotherapy for liver metastases from colon cancer

We studied recurrence after hepatic resection and prophylactic hepatic arterial infusion chemotherapy for liver metastases from colon cancer, retrospectively. Eighty-six patients underwent curative hepatic resection for liver metastases, and 41 of them received arterial infusion chemotherapy. Eight patients (20%) developed only remnant liver metastases, 6 patients (15%) had hepatic and extrahepatic recurrences, and 10 patients (24%) developed only extrahepatic recurrences. Regional therapy including hepatic resection for residual liver metastases should be indicated for recurrences after hepatic arterial infusion chemotherapy.     

Hepatic arterial infusion of chemotherapy for hepatic metastases from colorectal cancer.

BACKGROUND: Sixty percent of colon cancer patients develop liver metastasis. Only 25% of those have potentially resectable hepatic metastases, and approximately 58% of those patients relapse. METHODS: We review the indications and the technical aspects of hepatic artery infusion (HAI) of chemotherapy, as well as the efficacy, morbidity, and outcomes. RESULTS: HAI of chemotherapy has been used following hepatic metastasectomy, in patients with unresectable metastases, or in combination with other agents. Floxuridine, the chemotherapeutic agent most studied, is administered through an implantable subcutaneous infusion pump connected to a surgically placed hepatic artery catheter, which delivers the chemotherapeutic agents at a slow fixed rate. Treatment-related toxicities include chemical hepatitis, biliary sclerosis, and peptic ulceration. Some trials report a survival benefit for HAI over systemic chemotherapy with acceptable toxicity. CONCLUSIONS: Regional perfusion chemotherapy can be logistically and technically complicated to deliver. The development of newer systemic agents with superior efficacy in the treatment of metastatic colorectal cancer will likely diminish the role of regional perfusion therapy in the future.     

A case of advanced gastric cancer with multiple liver metastases responding completely to hepatic arterial infusion and systemic chemotherapies

A 41-year-old male complaining of epigastric discomfort visited another hospital for a medical checkup. Gastrointestinal fiberscopic examination revealed a type 3 lesion on the lesser curvature of the lower portion, and biopsy specimens showed tubular adenocarcinoma. Abdominal CT demonstrated multiple liver metastases. After receiving a low-dose FP chemotherapy via IVH catheter for 1 week, the patient undertook a distal gastrectomy accompanied by D2 lymph node dissection. From the 19th postoperative day (POD), hepatic arterial infusion chemotherapy (HAIC) using 5-FU (500 mg/day) plus CDDP (10 mg/day) was performed for about 14 months. On the 47th POD, oral administration of UFT began and continued for 2 years. After 4 months of HAIC, the metastatic lesions of the liver disappeared completely. The patient has been free from recurrence since then for about 2 years. In the peripheral blood, Th1/Th2 ratio and activity of NK/LAK (IL-2 induced) kept increasing during this period. IHAC using 5-FU plus CDDP seems to be an efficient and worthy therapeutic modality if there are no other lesions except multiple liver metastases and a curative gastric resection is indicated.     

Limited but definite efficacy of prophylactic hepatic arterial infusion chemotherapy after curative resection of colorectal liver metastases: A randomized study

BACKGROUND: Greater than 50% of patients who undergo curative resection of liver metastases from colorectal carcinoma develop recurrent disease in the residual liver. Although several studies have attempted to use hepatic arterial infusion (HAI) chemotherapy to prevent recurrence, to the authors' knowledge the efficacy of the treatment has not yet been determined. METHODS: Nineteen patients who underwent curative hepatectomy for metastatic colorectal carcinoma randomly were assigned into the HAI group (nine patients) or the control group (ten patients). Patients in the HAI group received continuous intraarterial infusion of 5-fluorouracil (5-FU) (500 mg/day) for 4 days followed by a 3-day rest. The treatment was continued for 6 weeks. RESULTS: The median follow-up period was 62.2 months. The recurrence was confirmed in three patients in the HAI group and in eight patients in the control group. Of these, recurrence in the remnant liver was observed in one patient and in six patients, respectively. The median disease free interval after hepatectomy was 62.6 months in the HAI group and 13.8 months in the control group. The 1-year, 2-year, and 3-year disease free survival rates were 77.8%, 77.8%, and 66.7%, respectively, in the HAI group and 50.0%, 30.0%, and 20.0%, respectively, in the control group. Significant prolongation of disease free survival was observed in the HAI group (P = 0.045). No patients in the HAI group reported any adverse effect of >/= Grade 2 (according to the National Cancer Institute Common Toxicity Criteria). Two patients in the HAI group and five patients in the control group were dead of disease at the time of last follow-up. The 1-year, 3-year, and 5-year cumulative survival rates for the HAI group were 88.9%, 77.8%, and 77.8%, respectively, whereas those of the control group were 100.0%, 50.0%, and 50.0%, respectively (P = 0.2686). CONCLUSIONS: This randomized study revealed that short term HAI of 5-FU after curative resection of colorectal hepatic metastases is effective in preventing the recurrence of disease without any serious complications.     

Reasonable approach for prophylactic hepatic arterial infusion chemotherapy after potentially curative surgery for colorectal liver metastases

The authors discuss the reasonable management of implantable ports and catheters after cessation of adjuvant hepatic arterial infusion (HAI) chemotherapy following curative resection of colorectal liver metastases. Local recurrence in the residual liver was observed in only 4 patients of thirty-two patients (13%). Although heparin administration into the port was regularly performed in 17 patients to prevent its occlusion, the ports were successfully maintained in only 9 patients at a median time of 11.8 months postoperatively, and only one patient received further regional chemotherapy for recurrent disease. These findings indicate that heparin administration to maintain the port brings little benefit. In the most recent 3 cases, we used a new Piolax W Spiral catheter and removed the catheter and port after cessation of adjuvant chemotherapy. No complication related to the procedure occurred, and patients' quality of life was well preserved, suggesting that this approach for HAI is reasonable and beneficial.