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.     

Three cases in which CR was obtained in residual metastatic lesions by intrahepatic arterial infusion after resection of hepatic metastases from colorectal carcinoma

We report three cases in which CR was maintained after infusion (WHF) was performed for residual metastatic lesions following resection of hepatic metastases from colorectal cancer. (Case 1) A 55-year-old female with sigmoidal cancer and hepatic metastases, H2 (4 lesions). Right lobectomy and partial resection of the left lobe were performed. On the third month following surgery, CT showed two lesions in the lateral segment of the left lobe, and WHF was then begun. One month after the start of infusion, the lesions calcified and following that, disappeared. Infusion was performed for 12 months and the total amount of 5-FU was 52.8 g. Eight years and nine months following surgery, the patient is currently alive and without recurrence. (Case 2) A 65-year-old male with rectal cancer and hepatic metastases, H3 (6 lesions). Four lesions were removed by hepatic resection; however, 2 deep lesions in S4 and S5 were left unresected. WHF was begun one month following surgery, following which the lesions were undetectable by either CT or US. Infusion was performed for 18 months and the total amount of 5-FU was 81 g. Two years and ten months after surgery an isolated lung metastasis was discovered in the right lung and a thoracoscopic partial resection was performed. Eight years and four months following the original surgery and five years and four months following the lung operation the patient is alive and without recurrence. (Case 3) A 55-year-old male with rectal cancer and subsequently discovered hepatic metastases, H3 (5 lesions). Resection of the lateral segment and a partial resection of the right lobe were performed; however, one deep lesion in S7 was left unresected. WHF was begun on the 10th day following surgery. At about eight months there was a change in shape and shrinkage of the lesion. Infusion was performed for 11 months and the total amount of 5-FU was 48 g. Ten months following surgery, CT showed a new lesion in S7 and a partial resection was performed. Intraoperative US confirmed the disappearance of the previous residual lesion in S7. One year and one month following the original surgery, the patient is alive and without recurrence. From these results, it is suggested that with postoperative WHF it is possible to obtain a complete cure in cases of colorectal cancer with hepatic metastases without the resection of all lesions. (*WHF: 5-FU 1,000 mg/m2/5 hrs/week).     

Radiofrequency ablation (RFA) in colorectal cancer with hepatic metastases

We considered the appropriateness of RFA, which was performed in three cases of colorectal cancer with hepatic metastases accompanied by liver cirrhosis. Case 1 involved a patient with sigmoid colon cancer ss, n1 (+) with severe hepatic dysfunction and synchronous hepatic metastases (S5, S6, S8) in which RFA was performed. After 1 year and 6 months, recurrence (S3, S4) was detected in the residual liver, and the patient is currently undergoing the IFL (CPT-11/5-FU/Leucovorin) treatment. In case 2, following a partial hepatic resection, RFA was performed for cecal cancer ss, n2(+) with synchronous hepatic metastases (S5, S6, S8). After 11 months, recurrence (S5, S6, S7) occurred in residual liver and again RFA was performed following a partial hepatic resection. Lung metastases have occurred and currently IFL (CPT-11/5-FU/Leucovorin) and WHF treatments are underway. In case 3, 4 years and 8 months after cancer of the descending colon ss, n1 (+), RFA was performed on asynchronous hepatic metastases (S5, S7, S8). The patient died of peritonitis carcinomatosa one year after RFA. In all three cases, metastases were identified by dynamic CT as low density masses with no blood flow. Necrosis in all three metastases and local control had been achieved. There were no severe complications. Under the current conditions, local coagulation methods including RFA are appropriate in those cases in which resection are not possible such as multiple metastases with severe hepatic dysfunction, etc.     

Three cases of multiple colorectal liver metastases responding to hepatic arterial infusion chemotherapy undergoing liver resection

We encountered three cases of multiple liver metastases of colorectal cancer treated with hepatic resection after hepatic arterial infusion. Case 1: A 55-year-old female underwent sigmoidectomy for sigmoid colon cancer and six liver metastases. After responding postoperatively to hepatic arterial infusion chemotherapy (HIA), she underwent resection of liver metastases. Case 2: A 66-year-old man underwent colectomy and hepatic resection for cecal colon cancer and liver metastasis. Multiple liver metastases appeared six months after the operation. HIA resulted in a complete response. Liver metastases recurred twice and liver resection was performed each time. Case 3: A 52-year-old female underwent partial resection of colon and liver for ascending colon cancer and multiple liver metastases. After she responded postoperatively to HIA and systemic chemotherapy, the patient underwent resection of liver metastases. Case 1 has lung metastases at this writing. The other two patients are alive and well, and have been free from recurrence as of 4 years after operation.     

Consideration of surgical treatment for recurrence after the resection of hepatic metastases from colorectal cancer]

We considered treatment for recurrence following the resection of hepatic metastases from colorectal cancer. The subjects of this study were 15 of 29 patients who had undergone WHF arterial infusion following resection of hepatic metastases from colorectal cancer, in whom there was a recurrence. Of these 15 cases, 6 involved recurrence in a single organ (residual liver, 4; lung, 1; local area, 1), 7 involved two organs (residual liver and lung, 2; residual liver and local area, 2; residual liver and bone, 1; spleen and intra-abdominal lymph node, 1; intra-abdominal lymph node and peritoneum, 1) and 2 involved three organs (lung, bone and abdominal wall, 1; lung, peritoneum and distal lymph node, 1). Reresection was performed in all cases in which recurrence occurred in a single organ. For those cases in which recurrence occurred in two or more organs, reresection and infusion were performed in the 4 cases of recurrence in the residual liver and reresection was performed in the case of recurrence in the spleen and intra-abdominal lymph node (No. 16), the case of local recurrence and the case involving the abdominal wall. The 5-year survival rate of the 29 cases who underwent initial hepatic resection was 61.9%. Five years following resection, the recurrence rate in the residual liver was 38.3%. The survival rates following treatment for recurrence were 76.9, 51.3 and 25.6% for 1, 3 and 5 years, respectively. Of the 8 deaths which have occurred to date, only one was directly related to an increase in hepatic metastases. Following resection of hepatic metastases from colorectal cancer, WHF provides a high rate of prevention as well as a high survival rate. Furthermore, with regard to recurrence following WHF treatment, if the recurrence is in only one organ, there is the possibility of achieving effective treatment by reresection (WHF = 5-FU 1,000 mg/m2 5 hrs qw).     

Serum carcinoembryonic antigen (CEA) correlates with the survival time during 5-FU hepatic arterial infusion chemotherapy for unresectable colorectal hepatic metastases

We investigated whether carcinoembryonic antigen (CEA) could be used to predict the response and survival of patients treated with 5-FU. Between 1984 and 1994, 58 patients with unresectable hepatic metastases from colorectal carcinoma were enrolled in this study. Forty-three patients underwent resection of the primary colorectal malignancy, and a catheter was inserted into the hepatic artery during the operation (HAI group). Fifteen patients received no adjuvant therapy (non-HAI group). Patients with CEA values reduced by greater than or equal to 30% at 2 months after the start of 5-FU infusion had a significantly longer survival period than patients with a decrease of <30%. Terminal cases in CEA reduced by greater than or equal to 30% group revealed that CEA re-elevation was observed at 7 months, and the patients died 8 months later at 15 months. Our findings suggest that serum CEA monitoring is useful for predicting the survival time following 5-FU hepatic arterial infusion.     

A case report of complete remission of liver metastases from colorectal cancer treated with continuous hepatic arterial infusion

We encountered a patient with liver metastases from colorectal cancer in whom continuous hepatic arterial infusion brought complete remission. A 58-year-old man was admitted to our hospital for advanced rectal cancer with multiple liver metastases. He underwent a low anterior resection (D2). Continuous hepatic arterial infusion of 5-FU (250 mg/day) with a weekly arterial infusion of MMC (4 mg) was performed for 14 days. Six continuous hepatic arterial infusions resulted in a complete remission. The patient has been free from any sign of recurrence for 37 months after the operation. Continuous hepatic arterial infusion using 5-FU and MMC seems to be effective in the treatment of multiple liver metastases from colorectal cancer.     

A case of unresectable liver metastases from rectosigmoid colon cancer with survival for over 3 years after multidisciplinary treatment

A 61-year-old man underwent curative low anterior resection for rectosigmoid colon cancer. Follow-up ultrasonography revealed unresectable multiple liver metastases at 10 months after surgery. Arterial infusion therapy with 5-fluorouracil (5-FU) was given at 1,500 mg every 2 weeks up to a total dose of 37.5 g, resulting in complete remission (CR) of the liver metastases. However, recurrence was seen 4 months after CR. Following partial hepatectomy and local ablation therapy, he received multidisciplinary treatment including local ablation therapy, arterial infusion of 5-FU and mitomycin C, and systemic chemotherapy with 5-FU/Leucovorin/CPT-11. The patient died of liver failure at 3 years and 7 months after the detection of hepatic metastases. If arterial infusion therapy achieves CR of unresectable hepatic metastases from colorectal cancer, the patient may survive for several years with multidisciplinary treatment including surgery, local ablation therapy, and systemic chemotherapy.     

A long survival case of sigmoid colon cancer patient with initially unresectable hepatic metastases

The prognosis of a colorectal cancer patient with unresectable hepatic metastases is extremely poor. To improve the prognosis, when the hepatic metastases were initially unresectable, we performed second-look hepatectomy (s-l hepatectomy) after neoadjuvant hepatic arterial 5-FU infusion plus UFT (HAI-PMC). Here, we report the case of a sigmoid colon cancer patient with initially unresectable hepatic metastases showing a prolonged survival (6.5 years) by second-look operation after HAI-PMC. A 57-year-old woman was diagnosed with sigmoid colon cancer with unresectable liver metastases. Sigmoidectomy and hepatic arterial catheterization were performed in the initial operation, and HAI-PMC was performed 6 months after. Metastatic foci of the liver had shrunk (90.9%), but solitary metastatic lung cancer was detected during HAI. As no other metastatic lesion was observed, partial resection of the liver and lung was performed as a second-look operation, 6 months after the initial operation. The woman continued venous infusion chemotherapy as an outpatient, and she survived for 6.5 years after the initial operation. This result suggests that strategic multidisciplinary treatment utilizing s-l hepatectomy after neoadjuvant chemotherapy can lead to better prognosis for colorectal cancer patients with hepatic 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.     

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.     

Long-term survival case after liver resection and postoperative hepatic arterial infusion for multiple liver metastases from rectal cancer

A 45-year-old man underwent a low anterior resection for rectal cancer [T3, N1, M0, Stage IIa: UICC]. He received a postoperative systemic chemotherapy with 5-FU and LV. Five months after the operation, multiple liver metastases were detected in the right hepatic lobe (S5, 6, 8). Right hepatectomy was performed. Seventeen courses of postoperative hepatic arterial infusion (HAI) chemotherapy (weekly high-dose 5-FU regimen) were performed without severe adverse events. He was still alive with no sign of recurrence for 69 months after hepatectomy. After liver resection for metastases of colorectal cancer, although a systemic chemotherapy has been mainly performed, HAI chemotherapy is one of the important options for prevention of local recurrence.     

A case of multiple hepatic metastases from colorectal cancer effectively treated by arterial infusion therapy with Leucovorin/5-FU

We report a patient with multiple hepatic metastases from colorectal cancer effectively treated by hepatic arterial infusion therapy (5-FU/LV therapy). The patient was a 55-year-old man with sigmoid colon cancer and multiple hepatic metastases, 5 cm in diameter, in both lobes of the liver. First, we locally controlled the sigmoid colon cancer by sigmoid colectomy (with D3 lymph node dissection). After resection of the primary cancer lesions and dissection of the lymph nodes, we treated the patient by systemically administering 4 courses of Leucovorin/5-FU (once weekly for 6 weeks per course) from a port-catheter system during hospital stay and in the outpatient clinic after hospital discharge. Assessment of therapeutic effects by CT showed CR in the patient. CEA levels, which were abnormal before and after surgery, decreased to normal at the end of chemotherapy. After 1 year, neither CT evidence of tumor enlargement in the liver nor re-increase in CEA levels has been noted. Although the patient experienced side effects such as pigmentation, grade 1 loss of appetite, and leukopenia, he was able to maintain his QOL in the absence of severe side effects.     

Two cases of multiple liver metastases from colorectal cancer which responded well to hepatic arterial infusion (HAI) using 5-fluorouracil and l-leucovorin

We present two cases of multiple liver metastases from colorectal cancer, which did not respond to hepatic arterial infusion (HAI) using 5-fluorouracil (5-FU 1250 mg/body weekly) alone, but responded to HAI using 5-fluorouracil (5-FU 750 mg/body weekly) and l-leucovorin (l-LV 50 mg/body weekly) achieving a complete response (CR). The first case: A 71-year-old man with Stage II rectal cancer who underwent lower anterior resection developed multiple liver metastases 5 months after the surgery. As the weekly HAl using 5-FU for nine courses showed no response, l-LV was combined, and the liver metastases disappeared after 10 courses to achieve CR. The second case: A 65-year-old man with rectal cancer, sigmoid colon cancer and multiple liver metastases underwent lower anterior resection. The weekly HAl using 5-FU for seven courses showed no response. By combining 5-FU to l-LV, the liver metastases disappeared after fifteen courses. No toxic event was observed. In these two cases, it was suspected that a reduced foliate may be responsible for the failure by the 5-FU treatment alone.     

Validity of two-hour continuous hepatic arterial infusion chemotherapy with low-dose 5-FU for unresectable liver metastasis from colorectal cancer

The significance of hepatic arterial infusion chemotherapy for unresectable liver metastases from colorectal cancer was evaluated in 50 patients, who received either of the following regimens: 1 shot 5-FU + epirubicin + MMC (FAM group); hepatic arterial infusion of 5-FU for 2 hours + MMC (MF group); hepatic arterial infusion of 5-FU for 2 hours (5-FU group). There were no differences in the clinicopathological backgrounds of the patients among the groups. The mean survival time was 10.3 months, 16.0 months and 16.2 months in the FAM, MF and 5-FU groups. The effective percentages were 0%, 40% and 31% in the FAM, MF and 5-FU groups and the survival time of the effective cases was 18.1 months and 21.8 months in the MF and 5-FU groups. The MF group and 5-FU group showed significant improvement in prognosis. Concerning side effects, myelo-suppression and gastrointestinal toxicity appeared frequently in the MF group. In conclusion, 2-hour continuous hepatic arterial infusion with low-dose 5-FU for unresectable liver metastases from colorectal cancer may be helpful for improvement of prognosis.     

Problems of case accumulation in a clinical trial of hepatic arterial infusion after resection of hepatic metastases: A summary of the study design and questionnaire survey of the participating centers in study no. 29-0003 of the Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC)

A randomized controlled trial of intermittent hepatic arterial infusion of weekly high-dose 5-FU (WHF) after resection of hepatic metastases from colorectal cancer was conducted to study the survival benefit of two regimens. Patients were randomly assigned to receive one of two arms after resection of hepatic metastases: the WHF arm (study group), 1000 mg/m2 of 5-FU administered over the course of 5 hr once a week by hepatic arterial infusion; or the CVI arm (control group), 300 mg/m2 of 5-FU administered as a continuous intravenous infusion daily for 5 days followed 2 days' rest. This study is the first randomized trial of hepatic arterial infusion chemotherapy with percutaneous hepatic catheter placement and assessment of liver drug distribution by CT angiography after resection of hepatic metastases from colorectal cancer in the world. Fifty-two centers participated, and 91 patients were enrolled. Although the target number of patients was not enrolled, problems of this study and future prospects for trials of hepatic arterial infusion after resection of hepatic metastases were assessed by questionnaire surveys of the participating centers.     

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.     

Adjuvant hepatic arterial infusion after curative resection of colorectal liver metastases using removable intra-arterial catheters with shape-memory alloy

BACKGROUND AND OBJECTIVES: Although there are some reports that adjuvant hepatic arterial infusion (HAI) chemotherapy reduces the hepatic recurrence following curative resection of colorectal liver metastases, problems of indwelling catheters after chemotherapy cessation remains unsolved. The usefulness of adjuvant HAI was investigated using a removable port-catheter system. METHODS: Spiral catheterstrade mark were attempted to be placed in 17 patients who underwent curative hepatectomy. The catheter contains a special shape-memory alloy at its tip, which allows stable fixation to the vascular wall without coiling so the catheter can be removed if necessary. 5-fluorouracil (5-FU) in total dose of 12 g was intra-arterially administered. RESULTS: W spiral catheterstrade mark were successfully placed in the hepatic artery by percutaneous approach in 82% of the patients. All patients underwent scheduled chemotherapy without serious adverse events. Reservoir-catheter system was removed easily and uneventfully after discontinuation of the chemotherapy. 3D-CT angiography revealed that the hepatic artery was well preserved with short-term chemotherapy. Postoperative hepatic recurrence was observed only in 18% of the patients with the median follow-up time of 19.9 months. CONCLUSIONS: Prophylactic 5-FU HAI using W spiral cathetertrade mark and subsequent catheter extirpation is a promising strategy following curative resection of colorectal liver metastases.     

Results of pharmacokinetic modulating chemotherapy in combination with hepatic arterial 5-fluorouracil infusion and oral UFT after resection of hepatic colorectal metastases

BACKGROUND: Pharmacokinetic modulating chemotherapy (PMC) is a new therapeutic concept in combination with continuous 5-fluorouracil (5-FU) infusion and UFT. UFT enhanced plasma 5-FU concentration and antitumor effects during 5-FU infusion. The authors report on their experiences with arterial 5-FU infusion and UFT after resection of hepatic colorectal secondaries. METHODS: Fifty-eight patients were divided into two groups after hepatectomy. Group A, 30 patients, underwent hepatic arterial infusion (HAI) via implantable port system with perfusion 5-FU for 2 consecutive days per week at 600 mg/m(2)/day, and oral administration of UFT at 400 mg/day for 5-7 days per week, repeated 10 times, and Group B, 28 patients, underwent oral administration of UFT at 400 mg/day for 6 months. All the patients were managed at the outpatient clinic at Hyogo College of Medicine, and recurrence, survival, and toxicity were documented. Plasma 5-FU concentrations during chemotherapy were detected using high performance liquid chromatography. RESULTS: Maximum plasma concentrations of 5-FU in Group A reached 144.0 ng/mL and in Group B 58.7 ng/mL. Cumulative 5-year survival rate after hepatectomy in Group A was 59% and in Group B was 27%. (P = 0.00001) HAI-PMC drastically decreased hepatic recurrence (median hepatic recurrence free times were 34.2 months in Group A vs. 18.4 months in Group B; P = 0.00002). Grade 3 toxicity in Group A was found in 3 patients CONCLUSIONS: Pharmacokinetic modulating chemotherapy was designed as a uracil-related biochemical modulation. HAI-PMC significantly decreased hepatic recurrence after curative resection. This new chemotherapy concept significantly improved prognosis in patients with hepatic colorectal metastases.     

A case report--combination chemotherapy with oral UFT and CPT-11, 5-FU, l-LV by hepatic arterial infusion for multiple hepatic metastasis from sigmoid colon cancer

A 64-year-old woman was diagnosed with multiple hepatic metastases from sigmoid colon cancer. She underwent resection of the colon and catheter insertion into the hepatic artery for arterial infusion in August 2006. She was then treated with postoperative combination chemotherapy consisting of UFT and CPT-11, 5-FU, l-LV. UFT was administered orally at 400 mg/body/day every day and CPT-11 was injected at 100 mg/body/week, 5-FU at 750 mg/body/week, and l-LV at 300 mg/body/week for 8 continuous weeks. After 2 months of the chemotherapy, the metastatic liver tumors disappeared. So hepatic arterial infusion with the same regimens was injected once every month 4 more times. Oral UFT was administered every day. After 6 months of the combined chemotherapy above, we judged the effects of the chemotherapy to be a complete response. Then the chemotherapy was followed by oral UFT only. As severe nausea and vomiting were seen in this patient with an initial dose of 150 mg/body/week of CPT-11 at first, we reduced the dose of CPT-11 to 100 mg/body/week. From then, outpatient care was possible because no severe events were observed. Combined chemotherapy consisting of oral UFT and CPT-11, 5-FU and l-LV by hepatic arterial infusion is suggested to be a new and effective treatment for multiple liver metastases from colorectal cancer.