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.     

伴有同时性肝转移结直肠癌的外科治疗

目的探讨伴有同时性肝转移结直肠癌的外科治疗及其适应证。方法收集经外科手术治疗的116例伴有同时性肝转移的结直肠癌患者的临床资料,进行生存分析,并通过单因素分析和Cox比例风险模型多因素分析确定患者预后的影响因素。结果116例患者均行结直肠癌原发肿瘤切除,18例行同期肝转移瘤切除。围手术期死亡2例(1.7%),术后发生并发症者17例(14.7%)。全组患者5年生存率为14.29%,肝转移瘤切除患者5年生存率为32.12%。多因素分析显示,肝转移瘤切除、腹腔扩散、介入治疗和全身化疗是影响预后的最主要因素。结论伴有同时性肝转移的结直肠癌患者,选择外科手术切除肿瘤病灶,并辅助综合治疗可延长患者的生存时间。     

A case of postoperative multiple hepatic metastasis from esophageal cancer successfully treated by surgical resection and hepatic arterial infusion chemotherapy]

A 66-year-old male who underwent radical resection for esophageal cancer (stage IV) was diagnosed with multiple hepatic metastasis 1 year and 3 months after the surgery. He underwent hepatic resection and received systemic chemotherapy (FAP: 5-FU, ADR, CDDP), as the post-operative adjuvant therapy. One year and 3 months later, there was a huge recurrence in the residual liver and hepatic arterial infusion chemotherapy (FAP) was performed. The recurrent lesion disappeared completely after 3 sessions of arterial infusion chemotherapy. The arterial infusion chemotherapy was continued in the outpatient clinic and the recurrent lesion is well controlled. At present, this patient has returned to social life, 2 years and 3 months after the hepatic resection. The utility of hepatic arterial infusion chemotherapy and hepatectomy for postoperative multiple hepatic metastasis from esophageal cancer was shown in the present case.     

直肠癌术后同时性肝肺转移个体化治疗的个案分析

结直肠癌肝转移患者自然生存时间为6~12个月,同时伴有肺转移的生存时间更短。单纯化疗后可延长至12~24个月。对于结直肠癌肝转移患者,绝大多数死于肝脏的病灶。结直肠癌肝转移行肝切除术者,5年生存率大约40%。根治性手术切除是治疗结直肠癌肝转移的最佳方法,放化疗亦具有重要价值。现介绍1例天津医科大学附属肿瘤医院经肝胆肿瘤科、肺部肿瘤科治疗的直肠癌术后同时性肝肺转移的病例,该患者经多学科的协作诊疗后效果较佳,报道该病例诊治经验以促进结直肠癌诊疗技术和经验的全面融合,推动多学科间的交流与合作。      

198例结直肠癌肝转移患者外科治疗的疗效分析

背景与目的:肝脏是结直肠癌常见的转移部位,35%的患者在确诊时已发生肝转移,肝转移患者的预后较差。尽管手术切除、化疗、射频消融术、介入治疗等手段应用于临床,但治疗效果不同。本研究探讨结直肠癌肝转移外科治疗的临床疗效。方法:对我院5年间经病理检查证实的198例结直肠癌肝转移患者的临床资料进行回顾性分析。根据治疗方法的不同进行分组:根治性切除组46例(23.2%)、姑息性切除组43例(21.7%)、手术探查组或最佳支持治疗组29例(14.6%)、肝动脉置泵化疗组41例(20.7%),全身化疗组39例(19.7%);对其生存期进行比较和统计学分析。结果:根治性切除组中位生存期37.1个月,5年生存率为31.2%;姑息性切除组的中位生存期14.3个月,5年生存率为0;肝动脉置泵化疗组的中位生存期21.3个月,5年生存期为7.5%;全身性化疗和探查组或最佳支持治疗组的中位生存期分别为18.7个月、6.3个月,均无5年生存者。根治性切除组与其他组比较,中位生存期有统计学意义(P<0.01)。结论:根治性切除是提高结直肠癌肝转移患者生存率的重要手段;姑息性切除治疗效果并不优于辅助性治疗,对于不能根治性切除的病例可采用肝动脉置泵化疗。     

Clinical outcome of intra-hepatic arterial infusion therapy for multiple liver metastases from colorectal cancer

Weekly infusion of high-dose 5-FU through the hepatic artery after resection of colorectal cancer was compared with resection alone in patients with multiple liver metastases. Twenty-seven patients (Group I) underwent hepatic artery infusion chemotherapy and 74 patients (Group II) underwent resection alone. The average survival time was 17.9 months in Group I and 8.5 months in Group II. One CR and 7 PR were achieved with arterial infusion therapy and the response rate was 29.6%. One- to three-year survivals were better in Group I than Group II.     

Hepatic resection for synchronous liver metastases of gastric cancer]

Since 1970, we have treated 125 patients with synchronous liver metastases from gastric cancer. We analyzed 4 of these 125 patients who underwent hepatic resection, and studied the indications for hepatic resection. There were 3 H1 patients and 1 H2 patient. Lateral segmentectomy was performed for 2 patients and partial segmentectomy was performed for 2 patients. Hepatic arterial infusion (HAI) chemotherapy followed by surgery was performed for patients, one of whom died of recurrence in the residual liver at 49 months. The other patient has survived without recurrence for 30 months. Two patients without HAI died after 11.3 months and 1.9 months, respectively. The survival time of 3 H1 patients who underwent hepatectomy was 30.2 months, while that of the other H1 patients without hepatectomy was 8.3 months. In conclusion, when local control is obtained during surgery and the liver metastasis is H1 in a patient with synchronous liver metastasis of gastric cancer, aggressive hepatectomy supported by HAI should be performed to improve the prognosis.     

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.     

Rescue chemotherapy using multidrug chronomodulated hepatic arterial infusion for patients with heavily pretreated metastatic colorectal cancer

BACKGROUND:

Hepatic arterial infusion (HAI) chemotherapy delivers a high concentration of drugs both to liver metastases and to healthy liver with specific, limiting, hepatobiliary toxicities. Relevant detoxification and cellular proliferation pathways are controlled by the molecular circadian clock in normal liver but not in advanced tumors. In this article, the authors report their experience with chronomodulated HAI chemotherapy as rescue therapy in heavily pretreated patients who had metastatic colorectal cancer.

METHODS:

Data from all consecutive patients with colorectal cancer liver metastases who received HAI with chronomodulated, multidrug chemotherapy regimens in the authors' center after failure on standard chemotherapy were reviewed for efficacy and safety.

RESULTS:

Twenty‐nine patients were treated, including 76% with liver metastasis only and 24% with liver and lung metastases. Seventy‐five percent of patients had received ≥3 chemotherapy lines, including intravenous, chronomodulated chemotherapy in 59% of patients. Patients received a median of 4 HAI courses (range, 1‐9 courses). The most frequent grade (according to National Cancer Institute of Canada Common Toxicity Criteria [version 3]) 3 and 4 nonhematologic toxicities were vomiting, diarrhea, abdominal pain, and fatigue. No severe hematologic or hepatic toxicities and no chemical cholangitis were reported. An objective tumor response was observed in 10 patients (34.5%), including 4 patients who subsequently underwent R0 or R1 hepatic resection. The median progression‐free survival and overall survival were 4.5 months (95% confidence limits, 2.4‐6.5 months) and 18 months (95% confidence limits, 5.8‐30.2 months), respectively.

CONCLUSIONS:

HAI chronomodulated chemotherapy had well tolerated activity in selected, heavily pretreated patients, and the authors believe it deserves to be assessed prospectively in clinical trials among patients who have less advanced disease. Cancer 2009. © 2009 American Cancer Society.     

The clinical outcome of mFOLFOX6 treatment for colorectal cancer patients who underwent resection of liver metastasis -comparison between synchronous and metachronous liver metastasis

Only a few reports have suggested the efficacy of adjuvant chemotherapy including oxaliplatin based regimens following surgical resection of liver metastases from colorectal cancer. Since an administration of mFOLFOX6 was approved to medical insurance for advanced colorectal cancer as adjuvant chemotherapy, we applied mFOLFOX6 treatment (6 to 12 courses) to the patients who underwent curative resection of colorectal liver metastasis. The subjects were 14 patients who underwent curative resection for synchronous or metachronous colorectal liver metastasis and received mFOLFOX6 treatment postoperatively from January 2006 to January 2011. We retrospectively analyzed the patient's characteristics, relapse free survival, overall survival, and adverse events in these patients. Synchronous liver metastasis was found in 5 patients, while metachronous liver metastasis was observed in 9 patients. There were no significant differences between these patients in terms of clinical characteristics, the relapse free survival and overall survival. All patients had some adverse events including bone-marrow suppression and diarrhea. Especially, grade 3 or higher bone-marrow suppression were recognized in 6 patients (42.8%). Neurologic toxicity (≤ grade 2) was observed in 10 patients (71.4%). Adjuvant chemotherapy with mFOLFOX6 treatment following surgical resection of synchronous or metachronous liver metastasis was safely administered. We will further examine the benefit of mFOLFOX6 treatment for the patients who undergo a surgical resection of liver metastasis in the future.     

Evaluation of hepatic resection for metachronous liver metastases from gastric cancer

To evaluate the effect of hepatic resection for metachronous liver metastases after resection of gastric cancer, the clinicopathological factors of gastric cancer, state of liver metastasis, surgical procedures for liver metastasis, and remote survival were studied. Between 1989 and 2001, 30 consecutive patients underwent hepatic resections (36 resections) for metachronous liver metastases. The patients included 25 men and 5 women, and the median age was 60 years old (range 46-86 years old). As for curability, curative A/curative B was 10/20, and H0/H1/H2 was 25/3/2. The mean period from initial surgery to the liver resection was 19.3 months (range 6.3-65.2 months), and the liver metastatic conditions were H1 for 27 patients and H2 for 9 patients. By number of liver metastases, 27 patients had 1 lesion, 24 patients had 2, and 5 patients had more than 3 lesions. Twenty-nine patients were negative and 7 were positive for lymph node metastasis. A partial resection was performed for 13 patients, a subsegmentectomy for 3 patients, a segmentectomy for 7 patients, a lobectomy for 8 patients, and an extended lobectomy for 5 patients. For all patients except those who had other causes of death, the overall mean survival time was 702 days and the 5-year survival rate was 26.4%. There were four 5-year survivors after hepatic resection. In conclusion, the main prognostic factor after resection of metachronous liver metastases was the existence of lymph node metastasis, and the remote survival of patients with abdominal para-aortic lymph node recurrence was poor. The type of liver resection was not a predictor of survival. The resection of liver recurrence was evaluated clinically, but we should maintain strict criteria and select adequate surgical procedures.     

Two-stage liver resection and chemotherapy for bilobar colorectal liver metastases.

BACKGROUND: A significant number of patients with colorectal metastatic disease confined to the liver are inoperable at assessment. For these patients, the outlook is poor. Chemotherapy can 'down-stage' some tumours and render them operable. The authors present a series of patients with inoperable disease despite down-staging with chemotherapy, who underwent a two-stage resection to clear their metastatic disease. METHODS: The case-notes of 11 patients who were found to have inoperable hepatic metastatic disease were identified using computerised medical records and mean hospital stay, survival and long-term follow-up data was noted. RESULTS: The mean follow-up from initial resection was 13.5 months (range of 5-20 months). Three deaths were recorded in the follow-up interval. Causes of death included recurrence of hepatic disease following completion of two-stage resection, progression of original hepatic disease leading to inoperability at second stage operation and recurrence of original primary colorectal tumour. The mean survival in the patients who died was 17 months (range of 15-19 months). The remaining patients are alive to date with six patients showing no evidence of hepatic recurrence, follow-up period of 13 months (range of 8-20 months). One patient developed de novo prostate cancer and is awaiting his second liver resection, and one patient has stable hepatic disease with no evidence of progression. CONCLUSION: Two-stage liver resection can prolong survival when compared to chemotherapy alone, with a recurrence rate equivalent to ablation techniques. Longer-term studies are needed for further evaluation.     

Les cancers colorectaux métastatiques dans le sud tunisien: étude clinique et résultats thérapeutiques

Purpose

The objective of this retrospective study was to discuss the epidemioclinical criteria and the therapeutic results relative to metastatic colorectal cancer.

Patients and methods

The study concerned 130 patients who presented with metastatic colorectal cancer at diagnosis or who had developed late metastasis. We reviewed the epidemioclinical records of all the patients. Treatment consisted in metastasectomy followed by chemotherapy or chemotherapy followed by metastasis resection if possible. Response and toxicity were assessed according to WHO criteria.

Results

There were 86 patients who were metastatic at diagnosis and 44 who had developed late metastasis. The mean age was 55.5 years (sex-ratio: 1.04). Patients were frequently symptomatic. Liver metastases were the most common, followed by lung, node and peritoneal localisations. Fifteen patients underwent metastasis resection first and 6 were resected after cytoreductive chemotherapy. First line chemotherapy was: LV5FU2 (37%), FOLFIRI (33%) and FOLFOX4 (30%) with an objective response rate of 28% (CR: 45%) and a mean remission duration of 17 months. Fifty-nine patients received second line chemotherapy and 14 received a third line. The median survival was 19 months for all treated patients and the mean survival in patients with resected metastasis was 40 months. The overall survival rate was respectively 43, 25.8 and 9% at 2, 3 and 5 years.

Conclusion

Our study was characterized by the frequency of synchronous metastasis, young age and symptomatic disease. Therapeutic results were satisfying and would be improved if there were more resecable metastases, as the rate in our sample was particularly low.     

肝脏部分切除术在复发性上皮性卵巢癌肝实质转移治疗中的价值

目的 探讨复发性上皮性卵巢癌肝实质转移患者行肝脏部分切除术的临床价值.方法 回顾性分析39例复发性上皮性卵巢癌肝实质转移患者的临床病理资料.结果 39例患者中,10例进行了肝脏部分切除术,29例仅行挽救性化疗.手术组患者的病变均为单叶,且病灶＜3个,与化疗组比较,差异有统计学意义(P＜0.05),在年龄、初次手术病理类型及病理分级、初次减瘤手术结果、初次治疗后的无瘤生存时间、肝转移瘤大小及肝转移时CA125水平等方面,差异均无统计学意义(P＞0.05).10例手术患者中,单纯行肝脏手术6例,同时行其他部位肿瘤细胞减灭术4例,其中7例减瘤手术满意.3例发生手术并发症,无手术死亡病例.8例肝脏病理切缘为阴性的患者中,局部复发6例,中位复发时间为术后12个月.减瘤手术满意的患者与行挽救性化疗的患者,肝转移后的中位总生存时间分别为26个月和9个月,肝转移后3年累积生存率分别为60.0%和16.8%,两组比较,差异有统计学意义(P＜0.05).结论 对存在肝实质转移的复发性上皮性卵巢癌患者施行包括肝脏部分切除术在内的满意肿瘤细胞减灭术,术后辅以化疗,有可能改善患者的预后.

Abstract：

Objective To investigate the validity of hepatic resection as a treatment option for hepatic parenchymal metastasis in patients with recurrent epithelial ovarian cancer. Methods A retrospective review of the clinicopathological and follow up data of 39 patients treated in our hospital from 1996 to 2008was conducted. Results Ten patients underwent partial hepatic resection for metastatic ovarian cancer.All the 10 patients underwent surgery were with unilobar metastasis and the number of tumors was lower than 3 (P ＜0.05).No significant difference existed in patient age,the primary pathology type and tumor grade,the rate of optimal primary cytoreductive surgery,the disease free survival after the primary therapy and the serum CA125 level at the liver metastasis when compared with the 29 patients accepted salvage chemotherapy(P ＞0.05).There were 7 patients who achieved optional surgery.The operation complication was 3/10 andthere was no perioperative mortality.There were 2 patients without postoperative chemotherapy in the 8 recurrent patients with microscopic negative margins.The median recurrence time was 12(5-24) months after the hepatic resection.The overall median survival periods after hepatic metastasis were 26 and 9 months and the 3-years cumulative survival rates were 60.0% and 16.8% for the optimal surgery patients including hepatic surgery and the salvage chemotherapy patients,respectively(P ＜0.05).Conclusion Hepatic resection for liver metastatic epithelial ovarian cancer is safe and may achieve long-term survival in patients after optimal second cytoreductive surgery.     

Extra- and intra-hepatic metastasis successfully treated with alternative chemotherapy with hepatic arterial infusion and systemic intravenous infusion after responding to hepatic metastasis from colon cancer by hepatic arterial infusion--a case report

A 72-year-old woman, who had the carcinoma of cecum with unresectable multiple liver metastases, underwent ileocecal resection and insertion of hepatic arterial infusion catheter. Hepatic arterial infusion (HAI) chemotherapy using Leucovorin. 5-FU caused to decrease liver metastases after an initiation of HAI. However, the metastatic nodule at the right lobe of lung was found. Then systemic chemotherapy with CPT-11 CDDP was performed alternately with HAI chemotherapy. After the initiation of revised regimen, all metastatic lesions were shrunk. We here in present the case of extra- and intra-hepatic metastasis successfully treated with alternative chemotherapy with hepatic arterial infusion and systemic intravenous infusion after responding to hepatic metastasis from colon cancer by hepatic arterial infusion.     

18FDG-PET evaluation correlates better than CT with pathological response in a metastatic colon cancer patient treated with bevacizumab-based therapy

Around 20-30% of patients with hepatic metastasis from colorectal cancer can undergo liver resection, but the increased response rate obtained with the addition of monoclonal antibodies to chemotherapy regimens could result in a higher rate of liver surgery. In this report we describe the case of a patient who underwent a liver resection after neoadjuvant treatment with capecitabine, oxaliplatin and bevacizumab and who achieved a complete pathological response of the liver metastasis. A preoperative CT scan demonstrated a partial response to the treatment while 18FDG-PET scan correctly evaluated the complete pathological response in the liver and detected an active interaortocaval lymph node metastasis. New specific studies are required to evaluate the imaging response in metastatic colorectal cancer patients especially after treatment with new, targeted agents.     

Evaluation of prophylactic hepatic arterial infusion chemotherapy after curative hepatectomy for metastatic colorectal cancer

We evaluated the effect of hepatic arterial infusion (HAI) chemotherapy after curative resection of liver metastases of colorectal cancer. A total of 161 patients underwent curative resection of liver metastases. Among them, 50 patients underwent HAI of 5-FU, and 111 patients had no HAI therapy. The 50% disease-free survival time (50% DFS) was 758 days and 342 days in the HAI group and the non-HAI group (logrank test, p<0.01), and the 50% overall survival time (50% OS) was 978 days versus 730 days (p<0.05), respectively. Among the 71 patients with multiple resectable metastases (H2 or H3), the HAI group had a significantly superior 50% DFS. HAI therapy seems to be an effective form of adjuvant chemotherapy after hepatic resection of metastatic colorectal cancer.     

Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy--an intergroup study.

PURPOSE: Despite technical improvements that have minimized the morbidity and mortality of hepatic surgery, the long-term outcome of resection of hepatic metastases of colorectal cancer remains poor, with the majority of patients experiencing treatment failure in the liver. Because arterial chemotherapy regimens targeted to the liver have demonstrated high response rates, an intergroup trial of adjuvant therapy for patients undergoing hepatic resection of liver metastases from colorectal cancer was initiated. PATIENTS AND METHODS: Patients with one to three potentially resectable metastases were randomized preoperatively to receive no further therapy (control arm, 56 patients) or postoperative hepatic arterial floxuridine combined with intravenous continuous-infusion fluorouracil (chemotherapy arm, 53 patients). After exclusion of patients identified as ineligible for the planned treatment at the time of surgery, there were 45 control patients and 30 on the chemotherapy arm. The study was powered to evaluate improvement in time to recurrence and hepatic disease-free survival, not overall survival. RESULTS: The 4-year recurrence-free rate was 25% for the control arm and 46% for the chemotherapy group (P =.04). The 4-year liver recurrence-free rate was 43% in the control group and 67% in the chemotherapy group (P =.03). The median survival of the 75 assessable patients was 49 months for the control arm and 63.7 months for the chemotherapy arm (P =.60). The median survival of all 109 patients was 47 months for the control arm compared with 34 months for the chemotherapy arm (P =.19) CONCLUSION: These data demonstrate that adjuvant intra-arterial and intravenous chemotherapy was beneficial in prolonging time to recurrence and pre-venting hepatic recurrence after hepatic resection of colorectal cancer.     

不同治疗方法对结直肠癌肝转移患者预后的影响

目的 探讨不同治疗方法对结直肠癌肝转移患者预后的影响.方法 对300例结直肠癌首发肝转移患者的诊治过程及肝转移后生存情况进行回顾性分析.结果 结直肠癌肝转移灶完全切除者、姑息切除者和无法切除者的肝转移后中位生存期分别为48、19和18个月(P=0.000).对于无法行肝转移灶完全切除的患者,肝转移后化疗联合局部治疗和不治疗患者的肝转移后中位生存期分别为23个月和6个月(P=0.000).一线治疗有效患者和无效患者的肝转移后中位生存期分别为24个月和16个月(P=0.000).单因素生存分析结果显示,原发肿瘤的治疗方式、肝转移灶的手术方式、肝转移后的综合治疗以及一线治疗的疗效均与预后相关(均P<0.05).多因素分析结果显示,肝转移灶的手术方式、肝转移后的综合治疗和肝转移后一线治疗的疗效是影响结直肠癌肝转移患者预后的独立因素(P<0.05).结论 肝转移灶完全切除、肝转移后进行综合治疗以及肝转移后一线治疗有效的结直肠癌肝转移患者预后好.     

A case of postoperative multiple hepatic metastasis from gastric cancer successfully treated by percutaneous microwave coagulation therapy and hepatic arterial infusion chemotherapy

A 61-year-old male who underwent radical resection for gastric cancer was diagnosed with multiple hepatic metastasis 2 years and 2 months after the surgery. He first underwent percutaneous microwave hepatic coagulation therapy with segmental hepatic blood flow occlusion and obtained complete coagulation of the main tumor. Consecutively, he received hepatic arterial infusion chemotherapy (FAP: 5-FU, cisplatin, adriamycin) against residual multiple hepatic tumors. These hepatic recurrent lesions disappeared completely after 3 sessions of arterial infusion chemotherapy. At present, this patient is alive with no recurrent lesions, 1 year and 6 months from the beginning of treatment for hepatic metastasis. Recently, we tried hepatic arterial infusion chemotherapy (FAP) in four cases in which the recurrence from gastric cancer was not only in the liver but elsewhere. The response rate (CR and PR) was 75% and no major side effects were observed. In conclusion, some cases can obtain longer survival if the multimoderate therapy including hepatic arterial infusion chemotherapy (FAP) and microwave coagulation therapy are effective.