A case of gastric cancer with multiple liver metastases that were completely responsive to hepatic arterial infusion chemotherapy]

A 70-year-old male was hospitalized with a diagnosis of gastric cancer. Multiple liver metastases were detected by CT scan and ultrasonography, but no other metastases were found. After distal gastrectomy with lymphadenectomy, an intra-arterial catheter was inserted and hepatic arterial infusion (HAI) chemotherapy was started with the following regimen: epirubicin, 40 mg (once in 4 weeks); MMC, 4 mg (once in 2 weeks); and 5-FU, 500 mg (once a week). Oral administration of 300 mg/day of tegafur-uracil (UFT) was given concurrently. The metastatic liver tumors were gradually reduced, and then disappeared. The patient has been free from recurrence after HAI. As gastric cancer tends to spread (e.g. peritoneal dissemination) more than colorectal cancer, the indication for HAI in cases of gastric cancer is limited. However, the present case suggests that it may be useful in achieving long-term survival for patients with metastases localized in the liver.     

A case of gastric cancer with multiple liver metastases responding completely to TS-1

We report a case of a 65-year-old male with stage IV gastric cancer accompanied by liver metastases, which showed a significant response after administration of TS-1. One hundred and twenty mg/body/day of TS-1 was orally administered without hospitalization. After 3 months, upper GI endoscopy showed improvement of primary gastric lesion, and cancer cells could not be detected under biopsy. After 2 months, computed tomography (CT) showed a reduction in the multiple liver metastases. Moreover, after 15 months, CT showed a complete regression of the multiple liver metastases, for a complete response (CR). The serum level of carcinoembryonic antigen (CEA) was reduced from 115 to within normal range. Noticeable critical adverse effects did not appear. Treatment on an outpatient basis, therefore, greatly contributed to his quality of life. We judged that TS-1 might be a candidate anti-cancer drug for first-line chemotherapy for advanced gastric cancer.     

A case of colon carcinoma with unresectable multiple liver metastases responding to various combined chemotherapies centering on hepatic arterial infusion therapy

We have experienced a case of colon carcinoma with unresectable multiple liver metastases responding to various combined chemotherapies centering on hepatic arterial infusion therapy. A 42-year-old female with descending colon carcinoma and synchronous unresectable multiple liver metastases underwent left hemicolectomy in September 2001. She was treated with chemotherapy centering on hepatic arterial infusion (HAI) following implantation of a reservoir in the outpatient setting. Pharmacokinetic modulating therapy (PMC), and HAI with Leucovorin/CDDP/5-FU and Levoforinate/CDDP/5-FU were conducted sequentially. Alternative HAI of 5-FU with intravenous infusion of Levoforinate and systemic irinotecan/CDDP were continued biweekly after release of the hepatic artery occlusion. Liver metastases shrunk after 6 months of treatment and were remarkably decreased in size in May 2003. Although 3 metastatic lesions existed in both lungs, good quality of life has been maintained in the 2 years following surgery.     

A case of advanced gastric cancer with multiple liver metastases completely responding to combination of paclitaxel and S-1

A 46-year-old female was admitted to Kagoshima University Hospital with a complaint of epigastralgia and dysphasia. Gastrointestinal scopy revealed advanced gastric cancer in the upper third of the stomach. Pathological diagnosis of the biopsy specimen was moderately-differentiated adenocarcinoma. Abdominal CT suggested multiple liver metastases, so a combination of biweekly paclitaxel(PTX)and S-1 was started. After five courses of this regimen, the liver metastases and primary tumor were remarkably regressed. PTX was discontinued because of a grade 3 adverse effect of numbness. Nevertheless S-1 monotherapy for liver metastases resulted in a complete response. She has been well without tumor re-growth for 4 years. The combination of PTX and S-1 may be an effective regimen for gastric cancer with liver metastases.     

A case of elderly advanced gastric cancer patient with multiple liver metastases effectively treated by hepatic arterial infusion chemotherapy

An 85 years old man was performed systemic chemotherapy after the palliative gastrectomy for unresectable gastric cancer with multiple liver metastases. The response evaluation revealed a progressive disease after 4 courses of first-line S-1 therapy and 3 courses of second-line paclitaxel therapy. At this point, metastatic lesions were still localized in the liver, so hepatic arterial infusion chemotherapy (HAI) was introduced as third-line therapy. Despite the marked reduction of all target lesions and reduced tumor marker level after 25 weeks of HAI without any adverse event, novel multiple metastatic lesions had appeared in the lung and celiac LNs, resulted in the cessation of HAI. Then he had suffered grade 3 mucositis oral and anorexia throughout 2 courses of fourth-line S-1 + CDDP therapy and fifth-line docetaxel therapy. Considering that the goal of treatment for unresectable gastric cancer patients is to delay developing symptoms and to prolong their life with the least adverse event, HAI could be an effective therapy.     

A case of advanced gastric cancer with multiple liver metastases responding to TS-1 and CDDP

A 44-year-old male presented to our hospital with abdominal pain. The upper endoscopy revealed advanced gastric cancer. On the abdominal CT, there was evidence of multiple, massive liver metastases. After total gastrectomy, the patient was treated with daily oral administration of 120 mg TS-1 for 4 weeks followed by 2 weeks' rest and 6 weekly infusions of 10 mg CDDP in an intra-hepatic artery as 1 cycle. On the follow-up CT, the liver metastases had decreased significantly both in size and number after 2 cycles. The current case suggests that TS-1 and CDDP may have a potent therapeutic efficacy in cases of advanced gastric cancer with multiple liver metastases.     

A case of colon cancer with multiple liver metastases effectively treated with hepatic arterial infusion followed by systemic chemotherapy

A 63-year-old female was diagnosed as descending colon cancer with severe liver dysfunction caused by multiple liver metastases. Her performance status (PS) was 3 because of liver dysfunction and high fever. Initially, hepatic arterial infusion (HAI) chemotherapy was started to reduce the size of metastatic tumors and to prevent a liver failure. After 10 courses of HAI chemotherapy, she recovered from liver dysfunction, and CapeOX plus bevacizumab regimen was started. A partial response of metastatic liver tumors was observed after 8 cycles of this regimen and metastatic lung tumors were disappeared. The patient was alive after 12 months with PS 0 and CapeOX was continued.     

A case of gastric cancer with liver metastases successfully treated with combination therapy of systemic and hepatic arterial infusion chemotherapy

A 67-year-old man was admitted to our hospital because of advanced gastric cancer associated with metastases to the liver, the lymph nodes along the lesser curvature and the infradiaphragmatic lymph nodes. As we considered the primary lesion and the liver metastases to be unresectable, we treated him with combination therapy of systemic and hepatic arterial infusion chemotherapy. The regimen of systemic chemotherapy consisted of cisplatin (CDDP) and UFT. Hepatic arterial infusion chemotherapy included 5-fluorouracil (5-FU), doxorubicin (DXR) and mitomycin C (MMC). We repeated this therapy six times. The size of the primary lesion and the lymph node metastases decreased significantly after the chemotherapy. The size of the liver metastases did not change, but they appeared to necrotize. The patient maintained a good quality of life during the therapy. He finally died of peritonitis carcinomatosa 18 months after the diagnosis. This case indicated that combination therapy of systemic and hepatic arterial infusion chemotherapy was effective in cases of unresectable gastric cancer associated with liver metastases.     

A case of gastric cancer with multiple liver metastases responding to combined hepatic arterial and aortic infusion chemotherapy with cisplatinum, 5-fluorouracil,and levofolinate calcium

A 64-year-old man who had type IIc-like advanced gastric cancer with multiple liver metastases was admitted to our hospital. He underwent combined hepatic arterial and aortic infusion chemotherapy with cisplatinum (CDDP), 5-fluorouracil (5-FU), and levofolinate calcium (l-LV). After 4 weeks (2 courses) of chemotherapy, a partial response was achieved for the hepatic metastasis. Therefore, distal gastrectomy, right hepatectomy combined with caudate lobectomy, partial resection of the hepatic right lobe, and microwave coagulation therapy of the residual tumor of the hepatic right lobe were performed. With this operation, all tumor cells were removed or killed. Histopathologically, almost all of the primary tumor was fibrous tissue, and only a few sections of moderately differentiated adenocarcinoma observed in the subserosal layer. In the periphery of the metastatic lesion, residual well to moderately differentiated adenocarcinomas were observed, and in the center, only necrotic tissue was seen. The postoperative course was uneventful. Now, one year and seven months after the operation, he is followed as an outpatient. Combined hepatic arterial and aortic infusion chemotherapy with CDDP, 5-FU, and l-LV is thought to be an effective regimen for advanced gastric cancer with multiple liver metastases.     

A case of gastric cancer with multiple liver metastases responding to TS-1

We report the case of a 58-year-old male with Stage IV gastric cancer accompanied by multiple liver metastases, which responded to chemotherapy using TS-1. The patient was treated with daily oral administration of 120 mg TS-1 for 4 weeks followed by 2 weeks rest as 1 cycle. After 4 cycles, most of the liver metastases had disappeared and serum CEA level was reduced from 140 to 53.9. The patient received chemotherapy at our outpatient clinic for 9 months during which time there was no regrowth after the first treatment. The current case suggests that TS-1 may have a potent therapeutic efficacy in cases of advanced gastric cancer.     

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.     

A case of successfully treated unresectable multiple liver metastases from colon cancer by hepatic arterial infusion chemotherapy and systemic chemotherapy

Sigmoidectomy was performed for a 69-year-old man with sigmoid colon cancer and unresectable multiple liver metastases. The histological diagnosis was undifferentiated carcinoma of sigmoid colon. Hepatic arterial infusion chemotherapy with 5 FU and systemic chemotherapy with CPT-11 were performed after the operation. A complete response (CR) was achieved for liver metastases. The recurrent sign was not found at 23 months after the operation. This combination therapy is expected to be an alternative treatment of colorectal cancer with unresectable multiple liver metastases.     

A case of postoperative liver metastases from gastric cancer successfully treated with hepatic arterial infusion of paclitaxel

A 69-year-old man underwent total gastrectomy for advanced gastric cancer in August 2001. After surgery, he was treated daily with UFT 300 mg. In October 2002, the tumor marker (CEA) increased in value, and CT revealed multiple liver metastases. Because there were no extrahepatic metastases, we attempted to use hepatic arterial injection chemotherapy. A reservoir was placed in the hepatic artery on November 12. Thereafter, intra-arterial injection of paclitaxel at 120 mg (80 mg/m2) was administered over one hour to the reservoir. This arterial injection chemotherapy was administered once weekly for 3 weeks followed by 1 week rest. After 3 courses, CEA decreased markedly and CT revealed remarkable tumor reduction which was thought to show a partial response (PR). After 6 courses, PR was continued. Adverse effects were only grade 1 alopecia and leukopenia. No major adverse effects were observed. These results suggest that hepatic arterial injection therapy with weekly paclitaxel is effective against recurrent gastric cancer with liver metastases.     

A case of advanced gastric cancer with multiple liver metastases partially responding to combination intra-arterial chemotherapy via the hepatic artery and abdominal aorta]

A 57-year-old female diagnosed with advanced gastric cancer with multiple organ metastases was treated by various intra-arterial chemotherapies. After surgical resection of the tumor, adjuvant chemotherapy was carried out. Continuously administered 5-fluorouracil of 250 mg/day made it possible to control the growth of the liver metastases. Extrahepatic metastases were kept under control by administering 30 mg of methotrexate, 750 mg of 5-fluorouracil and 30 mg of Leucovorin per/day/week, and 60 mg/day biweekly of cisplatinum via an abdominal artery infusion port. Owing to this multiple infusion route and chemotherapy regimen, the patient lived for 18 months after her first diagnosis of gastric cancer with multiple liver metastases. Although liver metastases may respond to hepatic arterial infusion chemotherapy, extrahepatic metastases lead to poor prognosis. Given the above results, intra-abdominal aorta chemotherapy may be effective for extrahepatic metastases since this method gives high concentration of the anticancer agents at tumor sites with a low incidence of side effects.     

A case of postoperative hepatic metastasis from gastric cancer responding to hepatic arterial infusion chemotherapy of paclitaxel

A 70-year-old man underwent total gastrectomy for advanced gastric cancer in January 2000. He was treated with UFT of 300 mg/day after surgery. In December 2000, liver metastasis was detected. In January 2001, treatment was switched to oral administration of TS-1 at 100 mg/day. In April 2001, there were no extrahepatic lesions. However, the metastatic liver focus showed progression of the disease (PD). TS-1 was discontinued. In May 2001, a hepatic arterial injection reservoir was inserted. Thereafter, arterial injection chemotherapy with 5-FU was administered. However, in November, liver dysfunction was exacerbated, and computed tomography (CT) revealed PD. Therefore, in December, the above chemotherapy was switched to arterial injection of paclitaxel at 100 mg, which was administered once a week for 3 weeks and discontinued for the subsequent week. In March 2002, hepatopathy had subsided at the end of the 4th course, the performance status (PS) improved and CT revealed a minor response. In June 2002, the condition deteriorated to PD. However, there were no side effects other than alopecia. During the administration period, treatment at the outpatient clinic could be safely performed. These findings suggest that hepatic arterial injection therapy with paclitaxel for liver metastasis after surgery for gastric cancer is a useful second line for 5-FU-resistant patients.     

A case of advanced gastric cancer producing alpha fetoprotein with multiple liver metastases responding to TS-1 after TAE]

We report a case of advanced gastric cancer producing Alpha Fetoprotein (AFP) with multiple liver metastases in which TS-1 is effective. Prognosis of gastric cancer producing AFP is well known to poor. A 74-year-old female was admitted complaining of anemia. She was diagnosed as having advanced gastric cancer with multiple liver metastases producing AFP by endoscopy, computed tomography and angiography. Her serum AFP level was 17,666 ng/ml and her serum CEA level was 5-2 ng/ml. After transarterial embolization (TAE), her family rejected her operation because it would not be curative. So, she was treated with TS-1, 40 mg, administered orally every day, followed by 14 days rest, as the first course. The next was TS-1, 80 mg orally administered for 6 courses. Her serum AFP level was down from 17,666 ng/ml to 94 ng/ml after 6 courses of TS-1. CT revealed that liver metastases did not change and endoscopy showed the primary lesion has diminished. Our report is the first to demonstrate that TS-1 is effective for patients with advanced gastric cancer producing AFP with multiple liver metastases.     

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.     

A case of AFP-producing gastric cancer after curative operation effectively treated with chemotherapies including hepatic arterial infusion therapy

A 63-year-old woman was admitted complaining of epigastralgia. An endoscopic examination revealed a Borrmann type 2 lesion at the greater curvature of the middle third in the stomach. Abdominal computed tomography detected no liver metastasis. The preoperative serum alpha-phetoprotein (AFP) level was elevated to 242.9 ng/ml. 5-fluorouracil (5-FU) was given 200 mg/day for 26 days orally. Distal gastrectomy with D3+ No. 16b1 lymph node dissection, cholecystectomy and hepatic arterial canulation were performed, and mitomycin C 20 mg was injected intravenously during the operation. Immunohistochemical staining of the specimen for AFP by the SAB method was positive in the cancer lesion. After the operation, FP (cisplatin 100 mg on day 1, 5-FU 750 mg on days 1-3) therapy of one course and intrahepatic arterial infusion therapy using adriamycin 10-20 mg every 2 weeks for 7 months were conducted. Moreover, the patient took UFT 400 mg/day for 26 months orally on an outpatient basis as an adjuvant chemotherapy. The only toxicity was neutropenia (grade 3), but it abated without an interruption in the chemotherapy. The AFP level declined gradually, and returned to the normal range 1 month after surgery. The patient is still alive with no sign of hepatic metastasis or recurrence 7 years and 7 months after the gastrectomy.     

A case of hepatic metastasis and local recurrence from rectal cancer responding to hepatic arterial infusion and systemic chemotherapy

A 71-year-old man underwent low anterior resection for rectal cancer. Two years after the surgery, liver metastasis and local recurrence were found on the CT scan. The first-line treatment was systemic chemotherapy (CPT-11 and 5'-DFUR). Effect was satisfactory for local recurrence, but a new liver tumor was found on the CT scan. The second-line treatment was a hepatic arterial infusion (5-FU) and systemic chemotherapy (UFT). After 4 courses, the liver metastasis was reduced, but after 5 courses, the liver tumors had enlarged. The third-line treatment was a hepatic arterial infusion (5-FU + levofolinate) and systemic chemotherapy (UFT). After 5 courses, the liver tumor disappeared, and no other recurrence was found on the CT scan.     

A case of advanced breast cancer with multiple liver metastases resistant to chemotherapy responding to high-dose toremifene

A 47-year-old woman was admitted to our hospital for advanced breast cancer with multiple liver metastases and liver dysfunction in January 2004. EC (EPI combined with CPA), weekly PTX, and AI were performed but were not effective for that tumor. Therefore, high-dose TOR was started. Liver dysfunction recovered after administration of TOR, and primary tumor and liver metastases were evaluated as a partial response (PR). The same therapy has been performed for six months with no evidence of deterioration.