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.     

A case of liver metastases of rectal carcinoid successfully treated with hepatic arterial infusion of methotrexate and 5-fluorouracil

Standard therapy for liver metastasis from colorectal carcinoid remains controversial because of the rarity of the disease. We report herein a case of rectal carcinoid with multiple liver metastasis successfully treated with hepatic arterial infusion of methotrexate (MTX) and 5-fluorouracil (5-FU). A 65-year-old woman underwent posterior pelvic exenteration and hepatic arterial catheterization for rectal carcinoid involving the vagina associated with multiple liver metastases. Hepatic arterial infusion of MTX (50 mg/body) and 5-FU (500 mg/body) was started and repeated with a frequency of twice a week postoperatively. After 40 cycles of this chemotherapy, all but the largest metastatic lesion disappeared, and the largest decreased in size by 53%. The partial response was maintained for 7 months. Her performance status did not deteriorate throughout the period of the chemotherapy. These results suggest that hepatic arterial MTX/5-FU is safe and worth trying in patients with liver metastases from colorectal carcinoid.     

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.     

直肠癌姑息性切除联合肝动脉栓塞化疗治疗晚期直肠癌的临床研究

目的 探寻直肠癌伴不能手术切除的肝转移的有效治疗方法.方法 回顾性分析我院行直肠癌姑息性切除加肝动脉多次栓塞化疗的26例直肠癌同时伴不能手术切除的肝转移患者的临床资料.26例患者均于术前1月先行肝动脉栓塞化疗1次,1月后再行直肠癌姑息性切除,术后1月再行肝动脉栓塞化疗,以治疗后CT复查肝转移瘤全部碘化油沉积为标准,每...     

Successful combination chemotherapy for a case of small cell carcinoma of the rectum with multiple liver metastasis

A 69-year-old-man with small cell carcinoma of the rectum and multiple liver metastases was admitted in December 1996. Poorly differentiated adenocarcinoma was preoperatively diagnosed in a biopsy specimen from the rectum. Chemolipiodolization using 50 mg DXR and 6 ml lipiodol was performed for the multiple liver metastases. Ten days later, he underwent rectal amputation including lymph node dissection combined with the implantation of reservoir for hepatic arterial infusion chemotherapy. After operation 5-FU (500 mg, days 1-5) and CDDP (10 mg, days 1-5) were injected for 3 weeks through hepatic arterial route. The metastatic lesions in the liver represented a good response to the chemolipiodolization, though the metastatic tumor in the liver S4 region did not disappear on CT scan. The histological diagnosis of the resected rectum revealed small cell carcinoma so we attempted additional chemotherapy according to the regimen for treatment of small cell lung cancer. ETP + CDDP therapy was performed, in which ETP (100 mg, days 1-3) and CDDP (80 mg, day 1) were intraarterially infused. After three courses of this therapy, he achieved a complete response (CR) for the liver metastasis. Two courses of ETP + CDDP therapy were additionally performed in the outpatient department, and treatment is currently continued by oral administration of ETP (75 mg/day). He has been free of the disease for 16 months with few side effects. The combination therapy of chemolipiodolization and hepatic arterial infusion chemotherapy with ETP and CDDP may assure a good prognosis for multiple liver metastases of small cell rectal cancer.     

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.     

Histological examination of the effect of hepatic arterial infusion of degradable starch microspheres mixed with adriamycin and mitomycin C for liver metastases of colorectal cancer--second report

We histologically examined the effect of hepatic arterial infusion of degradable starch microspheres mixed with adriamycin and mitomycin C (DSM therapy) for liver metastases of colorectal cancer. The subjects were 15 liver metastatic lesions from 9 patients with colorectal cancer who underwent potentially curative hepatectomy after DSM therapy. Ages were ranged from 36 to 71 years old (mean, 57). The ratio of male to female was 4 to 5. Six patients had synchronous lesion(s). A single injection dosage of the DSM therapy was comprised of 300-600 mg degradable starch microspheres, 30 mg ADM, and 10 mg MMC. Three lesions from the two patients who were given a single DSM therapy did not show any radiographical changes. In addition, histological examination of these lesions demonstrated a grade 1 effect. The radiographical effect of the 12 lesions from the 7 patients, who were given the DSM therapy at least three times, showed SD in 4 lesions, PR in 6 lesions, and PD in two lesions. Histological examination of these lesions demonstrated Grade 2 in 4 lesions and Grade 3 in 5 lesions. In conclusion, it was histologically confirmed that a repeated DSM therapy could cause satisfactory effects beyond expectations by radiographic imaging in patients with liver metastases of colorectal cancer.     

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.     

胃肠癌肝转移经肝动脉栓塞及皮下药盒持续灌注化疗的疗效初探

目的本研究观察经肝动脉栓塞化疗和(或)肝动脉插管持续灌注化疗治疗晚期胃肠癌肝转移的临床疗效.方法 22例无外科手术指征的晚期胃肠癌肝转移患者经肝动脉介入治疗共72次,单采取Seldinger法肝动脉内插管皮下埋置药盒持续灌注化疗48次,或先用吡柔比星(THP)60 mg/m2和DDP 50 mg/m2加入超液化碘油10～30 ml进行肝动脉栓塞化疗再联合肝动脉持续灌注化疗共24次.肝动脉插管灌注的方案:CF 200 mg/m2,d1,d14,静脉滴入;顺铂(DDP)50 mg/m2,d1,或用奥沙利铂100～130 mg/m2,d1,从皮下药盒处缓慢推入;5-Fu 2 000～2 500 mg/m2,d1,d14,装入美国百特公司的便携式输液泵持续动脉灌注48 h.结果总有效率(完全缓解 部分缓解)为59.0%.肿瘤负荷＜30%者的有效率为77.8%,明显高于肿瘤负荷＞30%者(46.2%,P＜0.005).本组患者主要不良反应为肝功能损害、发热及胃肠道反应等,经相应对症处理可缓解.结论经肝动脉栓塞及插管持续化疗是治疗胃肠癌肝转移的安全有效方法,值得临床推广.     

Long survival in a case of unresectable hepatic metastasis from rectal carcinoma treated with second-look hepatectomy plus pharmacokinetic modulating chemotherapy (PMC)

A 67-year-old female with rectal cancer and multiple liver metastases underwent low anterior resection by total mesorectal excision (TME), cholecystectomy and hepatic arterial cannulation in June 1995. She was treated with hepatic arterial infusion chemotherapy (HAI) (5-FU 600 mg/m2/day x 2 days/w) and oral UFT (400 mg/body, 5 days/w) once a week for 6 months on an outpatient basis. As the metastatic foci of the liver significantly decreased (83.3%) and extrahepatic disease were not observed, partial resection of the liver (second-look hepatectomy) was performed in March 1996. She continued arterial infusion PMC and venous infusion PMC as an outpatient. During the follow-up period a lung metastasis appeared in November 1997. Her regimen was changed to modified PMC with MMC (mitomycin C) and CPT-11. She has been managed at our outpatient clinic while the lung metastasis remained but with no liver metastasis for 57 months after the first operation, until the present. Second-look hepatectomy and PMC with a two-way port system was a useful option for unresectable hepatic metastases from colorectal carcinoma.     

A case of synchronous hepatic and multiple pulmonary metastases from rectal cancer responding completely to UFT therapy after resection of primary and hepatic lesions

We report a case of disease-free survival with uracil-tegafur(UFT)therapy after resection of primary and hepatic lesions from rectal cancer. A 64-year-old female had synchronous hepatic and multiple pulmonary metastases from rectal cancer. Image studies including colonoscopy, CT, MRI and PET-CT showed 2 metastases of lung(rt. middle lobe and lt. upper lobe) and a metastasis of liver(S6)in addition to rectal cancer(Rb, pSM, pN1, ly2, v1). Abdominoperineal resection+D3 of rectal cancer was performed, followed by chemotherapy with UFT for 28 days, and then partial resection of liver. Resected specimens of the liver demonstrated a histological Grade 2 with many CD3-positive lymphocytes. After surgeries, chemotherapy with UFT was continued, resulting in a CR for pulmonary metastases. The patient has been well without any sign of recurrence 5 years after first surgery. This case indicated that UFT was effective for hepatic and pulmonary metastases from rectal cancer, partially due to T cells(CD3+)infiltrating the 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.     

Combination of transarterial chemoembolization and endocrine therapy for liver metastases of breast cancer]

Nine patients with multiple metastases including liver from breast cancer were treated with transarterial chemoembolization through hepatic artery using 40-50 mg of 4'-epi-adriamycin and Lipiodol, followed by 800-1,200 mg/day of medroxyprogesterone acetate. Of 9 patients thus treated, there were 4 partial response (44%), 2 no change and 3 progressive disease. Duration of disease control ranged from 4 to 46 months (mean 24.5 months). Seven out of 9 patients died within 6 to 37 months (mean 15.3 months) after diagnosis of liver metastases. The 3- and 5-year survival rates were 45% and 11%, respectively. We conclude that this therapy is a useful treatment modality for controlling liver metastases of breast cancer.     

Combined hepatic-artery and portal-vein chemoembolization for colorectal cancer metastatic to the liver

The purpose of the study was to evaluate the results of combined (hepatic artery and portal vein) oily chemoembolization (OCE) in patients with unresectable colorectal liver metastases. Courses of combined OCE were given to 45 patients (1990-2000). For arterial OCE (n = 150), 40-100 mg doxorubicin mixed with 10-15 ml iodized oil and gelatin sponge was used. OCE of the portal vein (n = 118) included injection of doxorubicin-in-oil without sponge. Response to treatment (partial tumor decrease or stabilization) was reported in 80%. Serious complications occurred in 3 patients (7%) but there was no mortality. The mean and median survival rates for those patients who died were 20.2 and 17 months, respectively. The 1-, 2-, and 3-year survival rates were 83, 40 and 14%, respectively. These results were significantly better than those for arterial OCE alone or hepatic arterial infusion. Combined (arterial and portal vein) OCE with doxorubicin appears the most effective locoregional treatment for unresectable colorectal liver metastases.     

Histological evaluation of liver metastasis of colorectal cancer following hepatic arterial infusion with degradable starch microspheres and adriamycin/mitomycin C]

Little is known about the histological effect of hepatic arterial infusion with degradable starch microspheres (DSM), adriamycin (ADM), and mitomycin C (MMC) on liver metastasis of colorectal cancer. We histologically examined hepatic metastases resected following this therapy and investigated their relation to macroscopic changes in size. Neither a histological nor macroscopic effect was found in 2 patients receiving this therapy only one time. A 57-year-old woman with a solitary liver metastasis who received this therapy repeatedly (five times every 3 to 4 weeks) subsequently showed a partial response. She underwent hepatic metastasectomy 5 months after the end of the therapy. Histological examination showed that the greater part of the metastatic lesion was composed of fibrous tissues without any viable cancer cells. In conclusion, it should be noted that repeated infusions of DSM.ADM.MMC for liver metastases of colorectal cancer can have a marked histological effect even though the lesion does not show a complete response.     

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 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.     

Continuous infusion of hepatic arterial irinotecan in pretreated patients with colorectal cancer metastatic to the liver.

BACKGROUND: Irinotecan is an active drug in colorectal cancer. In patients with liver metastases, hepatic arterial infusion of irinotecan could theoretically result in higher exposure to the drug. In order to determine the efficacy of hepatic arterial irinotecan we conducted a phase II study in pretreated patients with liver metastases of colorectal cancer. PATIENTS AND METHODS: Patients with measurable liver metastases of colorectal cancer with World Health Organization performance status (WHO PS) <2 were treated with a 5-day continuous infusion of hepatic arterial irinotecan every 3 weeks at a dose of 20 mg/m(2)/day. RESULTS: Of the 25 patients included, 22 were evaluable for response. Three of 22 patients (13.6%) had a partial response, nine (40.9%) had stable disease and 10 (45.4%) had progressive disease. No complete responses were observed. Median time to progression was 2.8 (range 1.2-23.8) months. Major toxicities were vomiting and diarrhea. There was no major hematological toxicity. CONCLUSIONS: Five-day continuous hepatic arterial infusion of irinotecan 20 mg/m(2)/day has low activity in patients with liver metastases of colorectal cancer previously treated by chemotherapy.     

结直肠癌肝转移经肝动脉栓塞及持续灌注化疗的临床疗效

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

A case of effective multidisciplinary treatment with hepatic resection for synchronous multiple liver metastases from rectal cancer

A 56-year-old-man complained of abdominal pain, and was diagnosed as having advanced rectal cancer with synchronous multiple metastatic liver cancer (H 3) in July 1999. He underwent low anterior resection and hepatic partial resection (S 1, S 2+S 3, S 5, S 6, S 8) in August 1999. In addition, he underwent hepatic arterial infusion chemotherapy (HAI) 6 times at ADM 30 mg+5-FU 1,000 mg+MMC 16 mg between October 1999 and July 2000 for recurrent metastatic liver cancer. He has survived more than 6 years after the initial surgery. Multidisciplinary treatment with hepatic resection may well be a strategy for patients with multiple colorectal liver cancer, even though H 3 type of metastasis.