A case of multiple liver metastases from breast cancer successfully treated with intra-arterial administration of docetaxel

Docetaxel is an excellent agent with a high antitumor effect for the treatment of advanced/recurrent breast cancer. A 55-year-old female with metastatic liver tumors from breast cancer showed a remarkable response to intra-arterial administration of docetaxel (20 mg/week, or 40 mg/2 weeks). Since CT and MRI imaging revealed multiple metastases in the liver, intra-arterial chemotherapy was selected. No critical side effect was found during this chemotherapy. A CT scan 3 months after chemotherapy showed a partial response. We conclude that this intra-arterial chemotherapy using docetaxel will be safe and useful for liver metastases from breast cancer.     

Rate of growth of intraabdominal metastases from colorectal cancer

Monitoring the progression or regression of intraabdominal metastatic disease is required for knowledgeable management of chemotherapeutic regimens designed to treat metastases. Computerized tomography (CT) and CT with EOE-13, a liver contrast agent, allowed precise measurement of metastatic disease. The tumor doubling time of colorectal metastases in four patients was determined from serial CT scans of individual patients. Tumor doubling times of untreated patients varied from 50 to 95 days, and were in the same range for hepatic, lymph node, or intraperitoneal metastatic disease. These data may indicate that metastatic disease of colorectal cancer progresses at a faster rate in the peritoneal cavity than is reported for colorectal cancer metastatic to the lungs. The response to chemotherapy or progression of disease was also determined in treated patients. High resolution CT scanning with EOE-13 allowed calculation of tumor doubling times, and therefore more precise management of cancer patients with metastases.     

A case of metastatic brain tumor from prostatic cancer showing remarkable shrinkage following CDDP administration

A patient with brain metastases from prostatic cancer received chemotherapy using CDDP alone. A dose of 80 mg of CDDP was administered twice intravenously, followed by intra-arterial injections of 70 mg and 50 mg for the primary lesion over the course of three months. The main brain tumor showed a 70% decrease in size when estimated by CT, along with improvement of clinical symptoms related to the brain metastases. Intravenous injection of CDDP may thus have potential therapeutic value against metastatic brain tumors.     

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

A 56-year-old man who underwent distal gastrectomy at another hospital was admitted to our hospital because of advanced gastric cancer with synchronous liver metastasis. As we considered that the metastatic liver tumor was unresectable one, an intra-arterial catheter was inserted and weekly chemotherapy including methotrexate (MTX) (intra-venous) and 5-fluorouracil (5-FU) (intra-arterial) was started. The metastatic liver tumor was gradually reduced and resulted in partial response (PR) after 12 courses. Eight months later, the size of the metastatic liver tumor increased and lung metastasis occurred, so we started a new regimen of chemotherapy using CPT-11 (intra-venous) and CDDP (intra-arterial). After 4 courses of this regimen, we gained PR both in the metastatic liver and lung tumor. This case indicates that the combination therapy of systemic and hepatic arterial infusion chemotherapy is a treatment option in cases of advanced gastric cancer with liver metastasis.     

保留膀胱手术联合动脉化疗治疗浸润性膀胱癌的临床研究

目的 评价保留膀胱手术联合动脉化疗治疗浸润性膀胱癌的临床疗效.方法 2003年4月～2006年12月,对35例浸润性膀胱癌患者采用经尿道膀胱肿瘤电切或膀胱部分切除术联合GC(吉西他滨 顺铂)方案动脉化疗治疗,总结分析肿瘤控制情况、膀胱保存率和患者的生存率.结果 33例患者获随访,2例失访,平均随访24.3个月(3～45个月).27例无瘤生存,2例带瘤生存,4例死于肿瘤转移,2年生存率为88.8%;19例无复发及转移,5例浅表性复发,3例浸润性复发,6例转移;25例保留膀胱生存,4例行挽救性全膀胱切除,4例死亡,2年膀胱保存率为74.1%.全部患者对动脉化疗耐受良好,无严重全身和局部不良反应.结论 保留膀胱手术联合GC方案动脉化疗治疗浸润性膀胱移行细胞癌近期疗效满意,毒副作用轻,值得临床进一步观察研究.     

Intra-arterial infusion chemotherapy using an implantable reservoir in the treatment of hepatic metastases in colorectal cancer

With colorectal cancer, the therapeutic outcome for multiple hepatic metastasis extending to the bilateral lobe, even when various chemotherapies are administered, is extremely poor. For multiple hepatic metastases at our clinic, from November, 1985, through February, 1991, we used an implantable reservoir to administer intra-arterial infusion chemotherapy and reviewed the results. We treated 16 patients with hepatic metastases of colorectal cancer, H2 in 3 cases and H3 in 13 cases. When we used the reduction rate of the tumor diameter as seen by CT scan as a criteria for antitumor effectiveness, 1 case was CR and 3 cases were PR, for an efficacy rate of 25.0%. Changes in the serum CEA level were related to antitumor effectiveness. Among the evaluable cases, the 1-year survival rate was 60.0%, which was significantly more favorable than the 20.0% obtained in the systemic chemotherapy group (p less than 0.05). Given the above, although there are a few problems such as the kind and dose of drugs, the use of intra-arterial infusion chemotherapy with an implantable reservoir to treat hepatic metastases of colorectal cancer permits a form of chemotherapy providing a better QOL out of hospital.     

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.     

A combined treatment approach to management of hepatic metastasis.

Forty-eight patients with liver metastases were treated at Rhode ISland Hospital in a nonrandomized sequential manner between January 1972 and June 1977. Eight received 5 FUDR hepatic artery infusion, 14 hepatic irradiation, and 25 were planned for combined intra-arterial chemotherapy plus total hepatic irradiation. Those patients who successfully completed induction treatments had a median survival in the radiation only group of 140 days, in the intra-arterial chemotherapy group 270 days, and in the combined group 376 days. Hepatic radiation when combined with chemotherapy was well tolerated. Primary tumor site, disease duration, and degree of abnormality of liver function had no relationship to the response to treatment. The pretreatment performance level of the patient as determined by the Karnofsky Performance Index gave the best indication for potential response to combined therapy. Based on the results of this treatment and the reports of other series, it appears that the combination of intra-arterial 5 FUDR plus hepatic irradiation may offer prolonged and worthwhile palliation to appropriately chosen patients.     

Treatment sequencing for simultaneous colorectal liver metastases

Up to 25% of patients with colorectal cancer present with simultaneous metastases and the liver is frequently the only metastatic site. This review will review treatment sequence planning considerations—including metastatic burden, primary tumor site, chemotherapy response, and ability to perform minimally invasive surgery—for patients with simultaneous resectable colorectal liver metastases. In addition, this review will address conversion chemotherapy, combined vs staged surgeries, and their possible sequences.     

A case of long-term survival after undergoing S-1 based multidisciplinary therapy for liver metastasis of gastric cancer

We encountered a case of gastric cancer accompanied with liver metastasis, which had a good response to chemotherapy of S-1. A 68-year-old female was admitted to our hospital due to further examination of gastric tumor detected by an outpatient physician. She was found to have a type-3 gastric cancer in upper gastrointestinal endoscopy and a metastatic tumor of the liver in abdominal CT. Although chemotherapy of S-1 was inducted for the lesions, both the primary and liver tumors were dramatically reduced. We subsequently performed total gastrectomy and partial hepatectomy. Abdominal CT scan at 11 months after the initial operation revealed metachronous liver metastasis. She received combination chemotherapy of S-1 and CDDP. After 5 courses of the combination chemotherapy, the liver tumor disappeared. She has survived for 8 years without a recurrence after the initial operation. There was negative findings of immunostaining with thymidylate synthetase (TS), which was target enzyme for 5-FU at a biopsy sample of the primary gastric tumor before chemotherapy of S-1. TS immunostaining may be a useful marker for S-1 combined therapy for gastric cancer associated with liver metastases.     

Complete remission in a case of sigmoid colon cancer with multiple liver metastases-treatment with arterial chemotherapy and percutaneous microwave coagulation therapy

A 59-year-old man was admitted to our hospital for advanced sigmoid colon carcinoma with synchronous multiple liver metastases. The patient received sigmoidectomy with regional lymph node dissection on June 8, 1998. We started intra-arterial combination chemotherapy on July 1, 1998. MMC (4 mg/body) was administered via rapid intra-arterial infusion on day 1. After MMC administration, 5-day intra-arterial continuous infusion of 5-FU at 500 mg/body/day was performed with oral administration of LV (30 mg/body/day). The treatment cycle was defined as every three weeks. The patient was treated with 4 courses of chemotherapy. From September 30, he received intra-arterial infusion of bolus MMC 4 mg/body, LV 6 mg/body and 5-FU 1,000 mg/body/4 hrs every two weeks with oral administration of Tegafur-uracil 400 mg/day. After 4 intra-arterial chemotherapy sessions, the metastatic liver tumors disappeared except for a focus in the right lobe. Therefore we decided to give the remnant liver metastasis percutaneous microwave coagulation therapy (PMCT). He obtained a complete remission in the liver metastases after two PMCT (70 W, 60 sec) sessions. Intra-arterial chemotherapy is effective for unresectable metastatic liver tumors from colon cancer. If a patient shows a partial response on the metastatic tumors through the chemotherapy, one must consider other modalities such as PMCT.     

A successfully resected case of colorectal cancer with multiple liver metastases treated with FOLFIRI after failure of mFOLFOX6

A sixty-year-old man was admitted with anorexia and abdominal mass. Colonoscopy revealed type 2 tumor at sigmoid colon. Computed tomography (CT) demonstrated multiple liver metastases. The patient was diagnosed as sigmoid colon cancer with multiple liver metastases. The patient was treated with mFOLFOX6 as neoadjuvant chemotherapy because the liver metastases were unresectable. However, after 2 cycles of mFOLFOX6, the level of CEA and CA19-9 much increased. The regimen was replaced by FOLFIRI. The level of CEA and CA19-9 decreased after 2 cycles of FOLFIRI. CEA and CA19-9 further decreased and colonoscopy and CT revealed a partial response after 5 cycles of FOLFIRI. The patient was subjected to curative resection. Sigmoidectomy and liver resection were performed. Histological response was Grade 1b at liver metastasis. The patient was discharged and had an uneventful recovery. Six months after surgery, CEA and CA19-9 decreased to normal level, and the patient is free of recurrence. Neoadjuvant chemotherapy for metastatic colorectal cancer may render some unresectable patients resectable, affording these patients the possibility of prolonged survival. However, the optimal approach is unknown.     

Evaluation of intra-arterial infusion chemotherapy for liver metastases and lymph node metastases from gastric cancer--comparative analysis for intra-arterial group and non-intra-arterial group]

We evaluated the effects of intra-arterial infusion chemotherapy for liver metastases and lymph node metastases of gastric cancer. Of 410 patients undergoing gastrectomy in our department from July 1993 to December 2000, 29 (7.1%) had liver metastases. Intra-arterial infusion chemotherapy was carried out for 15 patients with liver metastases and 10 patients with lymph node metastases. There were 11 patients with liver metastases evaluated as follows: PR 5, NC 2, PD 4. Two patients with lymph node metastases were PR. In a comparison between the intra-arterial and non-intra-arterial chemotherapy group, it was observed among the patients with synchronous liver metastases that the survival period of the intra-arterial group was significantly longer than that of the non-intra-arterial group (p = 0.0164 logrank test). On the supposition that the survival period is counted from the day of computed tomography metachronous liver metastases was detected, in all liver metastases patients, the survival period of the intra-arterial group was significantly longer (p = 0.0212 logrank test). These results showed that the intra-arterial infusion chemotherapy is a useful treatment for gastric cancer patients with liver metastases.     

A case of multiple liver metastases from sigmoid colon cancer effectively treated by hepatic intra-arterial administration of levoforinate and 5-fluorouracil]

A 62-year-old female patient, who was diagnosed with sigmoid colon cancer with multiple liver metastases, was admitted to our hospital. She underwent sigmoidectomy with D3 lymph node dissection on January 31, 2000. In addition to that, she received hepatic intra-arterial infusion of levoforinate (l-LV) 250 mg and 5-fluorouracil (5-FU) 500 mg for combined multiple hepatic metastases starting on postoperative day 14, and these medications were administered over 48 hours once weekly by infuser pump. The tumor diminished by 59% 2 months after the start of administration and further diminished at 4 months. PR was achieved. Cancer metastasis to the cerebellum and metastasis to the lung were detected at month 9 and month 11, respectively, but the liver metastatic tumor continued to diminish in size, ultimately becoming undetectable by CT scan at month 10. Surgery and radiotherapy were performed for the cerebellar metastasis, and intravenous administration of a combination of l-LV and 5-FU was performed systemically for the pulmonary metastatic tumor. At present, the patient receives regular outpatient treatment continuously. To our knowledge, there has been no report on the combination therapy with l-LV and 5-FU through the hepatic artery. Since good antitumor efficacy was demonstrated in the present patient, this case is described in this report together with four other cases of hepatic metastasis from colorectal cancer.     

A case of gastric cancer patient with liver metastasis treated by radiofrequency ablation therapy combined with intra-arterial chemotherapy

We performed radio-frequency ablation (RFA) therapy combined with intra-arterial chemotherapy for a 71-year old female gastric cancer patient with liver metastasis. She underwent total gastrectomy due to advanced gastric cancer in July of 1996. Because CT scans revealed multiple liver tumors with her, she also underwent intra-arterial chemotherapy comprising of 5-fluorouracil, cis-platinum and Leucovorin. Although her liver tumors decreased in size and number, after 9 months, we had to remove the catheter because of hepatic artery obstruction. Immediately after the removal, 5 hepatic metastases appeared, which were 3.5 cm in maximum diameter. After RFA therapy, CT scans revealed homogenously attenuated lesions. Liver biopsy demonstrated a complete coagulation necrosis. She is currently alive going into 19 months after liver metastasis and 7 months after RFA.     

Liver-directed therapies in colorectal cancer

Colorectal cancer is the third leading cause of cancer-related deaths in the United States. Historically, the majority of patients that presented with metastatic disease to the liver were treated with systemic chemotherapy only but advances in imaging, surgical techniques, and non-resectional approaches have expanded the indications for liver-directed interventions. Current approaches used in patients with liver-only or liver-dominant metastatic disease include surgical resection, direct tumor ablation strategies, the use of intra-arterial infusions, and radiation therapies. The use of these liver-directed therapies in selected patients with colorectal liver metastases has led to significant improvements in overall survival. We review the clinical data and progress using liver-directed therapies in the treatment of colorectal 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.     

CPT-11 hepatic arterial injection plus oral UFT administration for liver metastasis of rectal cancer--report of two cases

The first patient was a 51-year-old male who had 5-fluorouracil-resistant recurrent rectal cancer with multiple liver metastases. He was given our new combination chemotherapy consisting of hepatic arterial injection of CPT-11 (20 mg/body) on day 1 and day 2 and oral administration of UFT (300 mg/day) on days 3 to 6 of a 7 day cycle starting in January 2001. Six weeks after the beginning of chemotherapy, the liver metastatic lesions were reduced. He is now living with outpatient treatment. The second patient was a 76-year-old male who had initial recurrent rectal cancer with multiple liver metastases. Thirty-two weeks after the same chemotherapy, the metastatic lesions had completely disappeared. Twelve months have passed since this chemotherapy, and we have not found any recurrent tumor. While significant antitumor effects were observed, there were few adverse events in either patient. These results suggest that combined chemotherapy of CPT-11 by hepatic arterial injection and oral administration of UFT is an effective treatment for liver metastases of rectal cancer.     

Regional yttrium-90 microsphere treatment of surgically unresectable and chemotherapy-refractory metastatic liver carcinoma

PURPOSE: The aim of this prospective study was to assess the safety and tumor response of intra-arterial Y-90 microspheres for the treatment of surgically unresectable and chemotherapy-refractory liver metastases. MATERIALS AND METHODS: Forty-six (46) patients with metastatic cancer to the liver from various solid tumors, with tumor progression despite polychemotherapy, were included. All patients had baseline computed tomography (CT), 18-Fluoro-2-deoxy-D-glucose-positron emission tomography (F-18 FDG-PET), hepatic angiography, and intra-arterial Tc-99m macroaggregated albumin (MAA) scan for the assessment of extrahepatic aberrant perfusion and lung shunting fraction. Twenty-seven (27) and 19 patients were treated with Y-90 glass- or resin-based microspheres (but not both), respectively, on a lobar basis and were monitored over 3 months after last treatment using dedicated attenuation corrected PET. For each patient, regions of interest (ROIs) were drawn along the liver edge to measure total liver standard uptake value (SUV) on axial images covering the entire liver for comparing pre- and post-treatment total liver SUV change. RESULTS: There was a significant decrement in total liver SUV after treatment by either glass- or resin-based microspheres (p = 0.0013 and 0.028, respectively). There was no significant difference in the amplitudes of the mean percentage reduction of tumor metabolism between these two agents (20% +/- 25% vs. 10% +/- 30% for glass- vs. resin-based microspheres; p = 0.38). None of the patients in the glass-based group developed complications, whereas 3 patients had complications related to hyperbilirubinemia (1 transient and 2 permanent) in the resin-based group. CONCLUSIONS: Results suggest that there is significant mean reduction of hepatic metastatic tumor load (metabolism), as evaluated objectively by PET after Y-90 microsphere, for the treatment of unresectable metastatic disease to the liver. The Y-90 therapy provides encouraging and safe results by arresting the progression of metastatic cancer to the liver with decreasing tumor metabolism.     

A case of multiple liver metastases from nonfunctioning neuroendocrine pancreatic tumor curatively resected after successful intra-arterial chemotherapy

We report a case of 33-year-old woman for nonfunctioning neuroendocrine pancreatic tumor with synchronous multiple liver metastases. For the primary pancreatic legion, we performed pylorus-preserving pancreatoduodenectomy at first. Three weeks after the surgery, the patient started to undergo intra-arterial chemotherapy with a weekly administration of high-dose 5-FU (1,000 mg/body) for residual liver metastases. Any severe adverse events were not observed. After 20 courses, a partial response was achieved and she underwent curative operation with partial resection for 4 metastatic legions and RFA for others. Histopathological findings of resected specimens revealed no viable neoplastic tissues. She is alive with no sign of recurrence 3 months after the surgery. Although a surgical resection is accepted as the standard therapy for liver metastases of nonfunctioning neuroendocrine pancreatic tumor, intra-arterial chemotherapy might be an alternative therapeutic option for unresectable case.