Extended right-sided liver resection for colorectal liver metastases—impact of percutaneous portal venous embolisation

AimTo compare the outcome after extended right liver lobe resection (ERL) for patients with liver metastases from colorectal cancer with preceding portal vein embolisation (PVE) with a non-PVE-group.MethodsNineteen patients underwent ERL (resection of segment 4–8) for colorectal liver metastases after PVE. They were compared with 21 patients that underwent an ERL without embolisation. A comparison was made with 84 patients undergoing right lobe liver resection during the same time period.Survival, post-operative morbidity and mortality were recorded and the volume of the future remnant liver (FRL) was measured with CT.ResultsThere were major complications in 1/19 patients in the PVE-group and in 6/21 in the non-PVE-group (p=0.04). No post-operative deaths were observed in the PVE-group, compared to three death in the non-PVE-group (p=0.09).The median survival in the PVE-group was 32 months, which did not differ from the non-PVE-group.In 21% of the patients that underwent PVE, progression occurred during the time between embolisation and surgery.There was no difference in survival for patients that underwent PVE followed by ERL, compared to patients that underwent standard right lobe liver resection.ConclusionThe survival of patients after ERL is comparable with patients that undergo standard right lobe resection and have less liver tumour.     

Chemotherapy plus percutaneous radiofrequency ablation in patients with inoperable colorectal liver metastases

AIM:To access the efficacy of chemotherapy plus radiofrequency ablation(RFA)as one line of treatment in inoperable colorectal liver metastases.METHODS:Eligible patients were included in three PhaseⅡstudies.In the first study percutaneous RFA was used first followed by 6 cycles of 5-fluorouracil,leucovorin and irinotecan combination(FOLFIRI)(adjunctive chemotherapy trial).In the other two,chemotherapy(FOLFIRI or 5-fluorouracil,leucovorin and oxaliplatin combination)up to 12 cycles was used first with percutaneous RFA offered to responding patients (primary chemotherapy trials).RESULTS:Thirteen patients were included in the adjunctive chemotherapy trial and 17 in the other two.At inclusion they had 1-4 liver metastases(up to 6.5 cm in size).Two patients died during chemotherapy.All patients in the adjunctive chemotherapy trial and 44%in the primary chemotherapy studies had their metastases ablated.Median PFS and overall survival in the adjunctive study were 13 and 24 mo respectively while in the primary chemotherapy studies they were 10 and 21 mo respectively.Eighty one percent of the patients had tumour relapse in at least one previously ablated lesion.CONCLUSION:Chemotherapy plus RFA in patients with low volume inoperable colorectal liver metastases seems safe and relatively effective.The high local recurrence rate is of concern.     

Hepatic arterial infusion chemotherapy for colorectal liver metastases

Hepatic metastases are a frequent complication of colorectal cancer. Resection of liver metastases can result in long-term survival. However, the majority of patients have unresectable disease. Alternative methods in Japan for treating these patients are hepatic arterial infusion (HAI) chemotherapy with administration of 1,000 mg/m2 of 5-FU over 5 hours. We summarize the status of HAI chemotherapy in terms of colorectal hepatic metastases today. HAI chemotherapy produced higher response rates compared with systemic chemotherapy, but did not demonstrate elongation of survival time in many trials. Important problems remaining to be solved are the technical aspects of percutaneous implantation of intraarterial catheters connected to a subcutaneous infusion reservoir and studies of combined therapy with systemic chemotherapy. Furthermore, in order to finally determine the position of HAI for colorectal liver metastases, it is necessary to conduct a comparative study versus systemic chemotherapy, using the survival time as the primary end point.     

不可切除结直肠癌肝转移的射频消融治疗

目的:总结射频消融(RFA)在不可切除结直肠癌肝转移(CLM)中的应用,并时治疗现状和发展前景进行分析.方法:检索PubMed及CHKD期刊全文数据库,以"结直肠癌、肝转移、射频消融、分析"为关键词,检索2001-01-2010-03有关"RFA对不可切除CLM中的应用及其价值"方面的文献,纳入分析26篇.结果:RFA单独或联合应用可提高不可切除CLM的疗效,尤其对于直径≤3 cm转移灶的疗效已经得到肯定.结论:RFA提高了不可切除CLM的总体疗效,但仍需要随机大样本循证医学证据,其疗效依赖于RFA技术水平的提高及医生经验的不断积累.     

Arteriovenous shunting in patients with colorectal liver metastases

The outlook for patients with colorectal liver metastases is poor. Microspheres have been combined with cytotoxics and administered via the hepatic artery in an attempt to improve tumour drug exposure within the liver. However, it has been suggested that arteriovenous connections might occur in association with intrahepatic tumours causing loss of regional advantage, and that the administration of microspheres further exacerbates arteriovenous shunting. In seven patients with colorectal liver metastases, base-line shunting was measured using a tracer quantity of radio-labelled albumin microspheres. The shunted fraction of a 'therapeutic quantity' of microspheres was subsequently measured in the same group of patients using albumin microspheres carrying a different radio-label. Base-line shunt for 0.5 x 10(6) microspheres was found to be 2.2 +/- 1.8% (mean +/- s.d.); the percentage shunt of a therapeutic quantity (40-80 x 10(6)) of microspheres was 3.0 +/- 0.8%. We conclude that arteriovenous shunting in patients with colorectal liver metastases is minimal, and is not significantly increased by the administration of therapeutic quantity of microspheres during regional chemotherapy.     

Clinical trial of prophylactic hepatic arterial chemotherapy for liver metastases in patients with Dukes' C colorectal cancer

Preliminary results of a prospective non-randomized trial of prophylactic hepatic arterial chemotherapy for liver metastases from colorectal cancer are presented. Twenty-two colorectal cancer patients (infusion group) in Dukes' C stage were given hepatic arterial infusion of 5-FU (500 mg/body for 1 hr per week, repeated 50 times) and peroral UFT-E (2.0 g/body, daily). Informed consent was obtained from all patients. Adverse effects and postoperative recurrence in the infusion group were compared with those of patients with UFT-E alone (control group). Complications related to hepatic arterial infusion in the infusion group were also demonstrated. There was no adverse effect in the control group, while diarrhea (grade 1) developed in one patient (5%) and pigmentation in five (24%) in the infusion group. Complications related to infusion were found in five patients (5%). Three patients in the infusion group presented with metachronous hepatic lesions, two of which were resected successfully. In the control group, one patient died of marked hepatic metastases, and one developed ovarian metastasis with lymph node involvement. Our regimen appears hematologically safe, however, the high frequency of pigmentation should be kept in mind. The oncological benefit of this chemotherapy would be clarified by a larger series of cases and longer follow-up.     

Hepatic arterial infusion chemotherapy for liver metastases from colorectal cancer

After randomized studies of hepatic arterial infusion chemotherapy (HAIC) versus systemic chemotherapy for liver metastases from colorectal cancer in the 1980s, the role of HAIC has been unclear and there is still no evidence to support it as the treatment of choice. The high local control, the differences in techniques between Japan and Western countries, the difficulty of detecting pre-treatment extra-hepatic metastases and the fact that HAIC does not control extra-hepatic lesions are the most important points in considering clinical trials of HAIC. Clinical studies on the combination of HAIC using 5-FU and systemic chemotherapy using CPT-11, and then randomized trial of systemic chemotherapy with/without HAIC is required in Japan to reveal the role of HAIC in the management of liver metastases from colorectal cancer. We should understand the importance of our role in this field.     

Neoadjuvant chemotherapy for patients with liver metastases from colorectal cancer

Colorectal cancer is the second most common type of cancer in industrialized countries. Despite improved resection procedures and optimized adjuvant chemotherapy, local or distant recurrences occur in 22-25% of patients with stage II/III colon cancer. Approximately 30% of patients have advanced disease at presentation. The liver is the most common site of colorectal metastases and, interestingly, 20-30% of patients with colorectal cancer have liver-only metastases. The combined modality of chemotherapy and surgery increases overall survival and the chance of cure for metastatic patients, even if there is no agreement in terms of the best schedule and how long the treatment must last. In this paper, we review the role and the rationale of neoadjuvant chemotherapy within a multimodal approach, and discuss remaining questions and future directions.     

First-line treatment with hepatic arterial infusion plus capecitabine vs capecitabine alone for elderly patients with unresectable colorectal liver metastases

This study aimed to compare the efficacy and safety of HAI fluoropyrimidine (FUDR)/capecitabine or single capecitabine as first-line treatment for elderly patients with unresectable colorectal liver metastases (CLMs). Fifty-one elderly patients with liver-only CLMs were eligible for enrollment. Patients were divided into HAI FUDR /capecitabine group and single capecitabine group randomly. The primary endpoint was median survival time (MST), defined as the time from the date of catheter implantation to the date of death or the date of the last follow-up. The secondary endpoint was objective antitumor response and adverse events. The HAI pump was implanted before chemotherapy. All patients received a 3-week cycle of oral capecitabin. In Group A, the RR and DCR were both 95.8%. In Group B, the RR and DCR were 48.1% and 81.5%, respectively. There was significant difference between the RRs of the 2 groups (P < 0.001). But there was no significant difference between the DCRs of the 2 groups (P = 0.053). There was a statistical difference between the MSTs of the 2 groups (18.5 vs.13 months, P = 0.0312). HAI FUDR combined with oral capecitabine as the first-line treatment for elderly patients with CLMs has promising efficacy and safety.     

A prognostic nomogram for colorectal cancer liver metastases after percutaneous thermal ablation

Purpose: To assess the efficacy of percutaneous thermal ablation in treating colorectal cancer liver metastases (CRCLM), and to propose a prognostic nomogram for overall survival (OS).

Materials and methods: Seventy-one patients with CRCLM undergoing thermal ablation at our institute from 2009 to 2013 were identified and analysed to formulate a prognostic nomogram. The concordance index (C-index) and calibration curve were calculated to evaluate the predictive accuracy of the nomogram. The nomogram was compared with two current prognostic nomograms for patients with CRCLM who had undergone hepatectomy (Kattan) and selective internal radiation therapy (Fendler). Predictive validity was assessed in the validation cohort of 25 patients who had undergone thermal ablation from 2014 to 2016.

Results: The median OS in the primary cohort was 26.4?months, whereas the 1-, 3- and 5-year OS rates were 72.2%, 37.2% and 17%, respectively. The median progression-free survival was 4.2?months. After univariate and multivariate analysis, a prognostic nomogram was formulated based on four predictors, including the number of tumours, maximum diameter of the tumour, CA19–9 level and ablation margin. The C-index of the nomogram was 0.815. Based on the patients of this study, the C-index was significantly higher than that of the Fendler nomogram (C-index, 0.698) and Kattan nomogram (C-index, 0.514, p?Conclusions: Thermal ablation was an effective therapy for CRCLM. Moreover, the nomogram was effective and simple for CRCLM patients undergoing thermal ablation.     

Glass yttrium-90 microspheres for patients with colorectal liver metastases.

Total calculated uniform liver doses of up to 150 Gy were achieved using glass yttrium-90 microspheres administered via the hepatic artery and targeted to tumour using angiotensin II in seven patients with colorectal liver metastases. No toxicity was observed. Hepatic metastatic progression was delayed in six patients. Median survival was 11 months (range 5-25 + months).     

Preoperative ultrasonography screening for liver metastases of patients with colorectal cancer

The clinical value of preoperative ultrasonography in screening for synchronous liver metastases was prospectively evaluated in 338 patients with colorectal cancer. Synchronous liver metastases were observed at laparotomy in 11.5% (39/338) of the patients. The liver metastases had been found by preoperative ultrasonography in 30 patients and missed in nine. The overall accuracy rate, sensitivity and specificity, and the positive and negative predictive values of this modality were 0.970, 0.769, 0.997, 0.968 and 0.971, respectively. In detecting liver metastases, the results were superior to those of biochemical blood tests and measurements of carcinoembryonic antigen serum levels. The accuracy of the ultrasonography was also superior to that of these other tests combined. The results indicate ultrasonography to be an indispensable preoperative examination for patients with colorectal cancer.     

肝动脉化疗栓塞与静脉化疗治疗结直肠癌肝转移的疗效

目的 通过比较TACE术与静脉化疗2种治疗方法对结直肠癌肝转移的近、远期疗效,从而探讨有效的治疗手段.方法 回顾性分析自2002年1月至2008年12月在广西医科大学肿瘤医院进行TACE、静脉化疗治疗的62例结直肠癌肝转移患者,其中TACE组17例,静脉化疗组45例,对比其近期疗效和随访其生存状况.结果 TACE组和静脉化疗组的近期有效率分别为64.7%、33.3% (P＜0.05).1年生存率分别为82.4%、59.6%;2年生存率分别为32.4%、19.3%;3年生存率分别为12.9%、7.4%;5年生存率均为0%(P均＞0.05).结论 对于不能或不愿手术的结直肠癌肝转移病人,TACE术或静脉化疗是可选择的有效治疗方案.TACE术较静脉化疗在近期疗效上显示出一定的优势,但在延长生存期上则无差别.     

The role of chemotherapy in the treatment and prophylaxis of colorectal liver metastases

Although colorectal liver metastases are a common occurrence, the role of chemotherapy in the management of this condition remains controversial. This article reviews the value of chemotherapy in the treatment and prevention of colorectal liver metastases. Systemic chemotherapy is of no proven benefit in terms of patient survival. Regional approaches to therapy are only a little more encouraging, although an objective view is difficult due to the lack of suitable randomized controlled trials and the difficulty in comparing results of different studies. More recent attempts to enhance regional therapy with degradable starch microspheres have theoretical advantages but need further clinical evaluation. Ultimately, more effective means of controlling overt or occult extrahepatic disease are also required when treating established liver metastases. The use of adjuvant intraportal chemotherapy for the prevention of liver metastases is more encouraging, however, and appears likely to have an important role.     

Chemotherapy in patients with resectable liver metastases from colorectal cancer

New chemotherapy drugs and, more recently, targeted therapies have significantly improved the outcome of patients with resected stage III colon cancer (adjuvant chemotherapy) and patients with unresectable metastases (palliative therapy). These advances raise several questions about the place of chemotherapy after and before surgery in patients with resectable liver metastases. To date, only a combined intra-arterial plus systemic fluoropyrimidine-based chemotherapy regimen has clearly demonstrated a relapse-free survival benefit. Yet, this approach is restricted to specialized centers, mainly because of technical difficulties and locoregional toxicities. The role of systemic use of oxaliplatin- and irinotecan-based regimens is currently under investigation. Planned trials will assess the role of anti-angiogenic and anti-epidermal growth factor receptor agents. We review the main trials performed in patients with resectable metastases, and discuss their potent impact on clinical practice.     

Determinants of survival in patients with unresectable colorectal liver metastases

Prognostic indicators in 67 patients with unresectable colorectal liver metastases were analyzed. These patients were identified to have isolated hepatic metastases after extensive radiological evaluation and demonstrated good performance status without evidence of liver failure. Univariate analysis revealed 6 of 22 factors that were associated with survival: alkaline phosphatase (AP), lactic dehydrogenase (LDH), occult intra-abdominal extrahepatic disease, percent hepatic replacement by tumor (PHR), sex, and carcinoembryonic antigen (CEA). A multivariate analysis identified two independent factors that jointly influenced survival: AP and PHR. Patients with an AP greater than 175 U/liter had a greater than threefold relative risk of dying compared with patients with AP less than or equal to 175 U/liter (P = 0.0001). Patients with PHR II or III (25-75%, greater than 75%) also had a greater than threefold relative risk of dying compared with patients with PHR 1 (less than 25%; P = 0.0074). Our patient population is typical of that being entered into trials examining experimental therapies. Alkaline phosphatase and extent of liver involvement by tumor are significant prognostic indicators that should be accounted for in such studies.     

The efficacy and limitation of hepatic arterial infusion chemotherapy for colorectal liver metastases

We investigated the efficacy and limitation of hepatic arterial infusion (HAI) chemotherapy for colorectal liver metastases. In terms of prophylactic HAI following curative resection of liver, the 5-year disease-free survival of HAI group (12 g of 5-FU administered in 6 weeks) was 66.7%, whereas that of randomly selected control group was 20.0%. The difference was statistically significant (p = 0.045). Recurrent disease was confirmed in three cases of HAI group (one in liver) and in 8 patients of the control group (6 in liver). However, the overall survival was not significantly different between the groups. Thus, the short-term HAI of 5-FU is effective in decreasing the recurrence of disease. As for the treatment of unresectable liver metastases, some patients received HAI of 5-FU (1,000-1,500 mg/w) showed prolonged survival with partial remission of the disease. However, the 1-, 2-, and 3-year cumulative survival of HAI group (n = 27) was 69.3, 34.1 and 11.4%, respectively, against 61.3, 22.6 and 9.4%, respectively, in the transarterial embolization (TAE) group (n = 31). Therefore it is important to estimate the effect in the early phase of HAI, and aggressively continue the treatment in selected patients for whom it is suitable.     

Modern insights into hepatic arterial infusion for liver metastases from colorectal cancer

Hepatic arterial infusion (HAI) selectively achieves high drug exposure of liver metastases from colorectal cancer. Such pharmacologic advantage has doubled the response rate of liver metastases on fluoropyrimidines (FP) delivered as HAI rather than intravenously, in a meta-analysis of randomised clinical trials (RCT). However, the improvement in antitumour efficacy did not consistently translate into any significant survival advantage across all randomised studies. However, the results of this meta-analysis should be cautiously interpreted due to the heterogeneity of the studies, inadequate study designs, obsolete therapy and high rate of early treatment discontinuation due to HAI technical failures or hepato-biliary toxicity. Most studies actually were performed before year 2000 and did not integrate the considerable progresses accomplished in the management of CRC, such as multidrug regimens instead of single agent FP and secondary resection of metastases, a major contributing factor for prolonged survival. Furthermore, the systemic exposure of patients given HAI was low without concomitant IV therapy, facilitating extra-hepatic relapses. The role of HAI in liver metastases from CRC should, therefore, be revisited, using modern multidisciplinary therapeutic approaches and appropriate study designs. Recommendations for the design of future RCTs exploring HAI are provided.