Treatment for multiple bilobar liver metastases of colorectal cancer

Background Recent advances have extended indications for hepatectomy to include multiple bilobar colorectal liver metastases (CLM). Staging systems based on the biological malignancy of primary and metastatic tumors provide appropriate indications for hepatectomy in CLM. However, suitability for resection in patients with complex and extensive hepatic metastases is controversial. Methods A medline search was performed to identify papers reporting the resection for CLM. Techniques, indication, and results were reviewed. Results If the anticipated remnant liver volume is small (25–40% of total), suggesting a high risk of postoperative liver failure, portal vein embolization (PVE) is recommended prior to hepatectomy. However, curative resections are not always possible. Specifically in synchronous multiple bilobar CLM, two-stage hepatectomy, comprising bilateral hepatectomy and primary resection with or without PVE, can prevent growth of ipsilateral metastatic nodules in the remnant liver and reduce surgical risk. Several local ablation techniques can complement surgery if hepatic resection alone increases the risk of postoperative liver failure or is not curative. Chemotherapy combined with targeted treatment can suppress recurrence and extend indications for hepatectomy by reducing the size and number of primary irresectable tumors. Conclusion PVE or staged procedure combining with local ablation or neoadjuvant, downstaging or adjuvant therapies extends indications for hepatectomy to include multiple bilobar CLM. The 5-year survival rate for multiple bilobar CLM treated with alternating hepatectomy and chemotherapy is comparable to the values reported for single and hemilateral CLM.     

Multimodal treatment options for bilobar colorectal liver metastases

Purpose  

We evaluated individualized multimodal oncological strategies in patients with bilobular colorectal liver metastases (biCRC-LM) as well as their effect on R0 resection rates, disease-free survival (DFS), and overall survival (OS).     

Survival after resection of multiple bilobar hepatic metastases from colorectal carcinoma

OBJECTIVE: To define the long-term outcome and treatment complications for patients undergoing liver resection for multiple, bilobar hepatic metastases from colorectal cancer. METHODS: A retrospective analysis of 165 consecutive patients undergoing liver resection for metastatic colorectal cancer was performed. Patients were divided into a simple hepatic metastasis group, consisting of patients with three or fewer metastases in a unilobar distribution, and a complex hepatic metastases group, consisting of patients with four or more unilobar metastases or at least two bilobar metastases. RESULTS: The 5-year survival rate was 36% for the simple group and 37% for the complex group. Multivariate analysis revealed that the number of hepatic segments involved by tumor and the maximum diameter of the largest metastasis correlated significantly with the 5-year survival rate. The surgical death rate was 4.9% for the simple group and 9.1% for the complex group; this difference was not significant. Multivariate analysis revealed that extended lobar resection and concomitant colon and hepatic resection were significant and independent predictors of surgical death. The combination of extended lobar resection and concomitant colon resection was used significantly more frequently in the complex group than in the simple group. CONCLUSIONS: Resection of complex hepatic metastases, as defined in this study, results in a 5-year survival rate of 37% and confers the same survival benefit as does resection of limited hepatic metastases. The surgical death rate for this aggressive approach is significantly higher if extended lobar resections are necessary and if concomitant colorectal resection is performed. Patients who have complex hepatic metastases at the time of diagnosis of the primary colorectal cancer and who would require extended hepatic lobectomy should have hepatic resection delayed for at least 3 months after colon resection.     

Hepatic resections for bilobar liver metastases from colorectal cancer

The present study was performed to assess survival benefits in patients who underwent a hepatic resection for isolated bilobar liver metastases from colorectal cancer. Thirty-eight patients underwent a curative hepatic resection for isolated colorectal liver metastasis. Among them, 11 patients had bilobar liver metastases and 19 had a solitary metastasis. The remaining 8 patients had unilobar multiple lesions. We investigated survival in two groups those with bilobar and those with solitary metastatic tumors. Survival and disease-free survival were 36% and 18% at 5 years, respectively, in the patients with bilobar liver metastases, while these survivals were 43% and 34% in the patients with solitary liver metastasis. In the 38 patients, repeated hepatic resections were performed in 15 patients with recurrent liver disease. The 5-year survival and disease-free survival rates for these patients were 38% and 27%, respectively, after the second hepatic resections. Of the 11 patients with bilobar liver metastases, 5 underwent a repeated hepatic resection, and they all survived for over 42 months. Based on our observations, a hepatic resection was thus found to be effective even in selected patients with either bilobar nodules or recurrence in the remnant liver. Received: February 7, 2000 / Accepted: April 26, 2000     

Perioperative complications after hepatectomy with or without intra-arterial chemotherapy for bilobar colorectal cancer liver metastases

BACKGROUND: We investigated perioperative complications of hepatic arterial infusion chemotherapy preceding major hepatectomy for multiple bilobar colorectal cancer metastases. No consensus exists concerning operative feasibility or perioperative course in patients undergoing major liver resection with neoadjuvant chemotherapy--partly because such chemotherapy is considered hepatotoxic, increasing the risk of postoperative liver failure. METHODS: Clinicopathologic data were available for 41 consecutive patients with 5 or more bilobar liver metastases from colorectal cancer who underwent major liver resection with or without prior hepatic arterial chemotherapy. Data concerning operative feasibility, postoperative liver function, complication rates, and histologic findings in the non-neoplastic liver were analyzed retrospectively. RESULTS: Prehepatectomy and postoperative day 1 platelet counts were lower (P < .01 and P < .05), alkaline phosphatase on postoperative day 3 was higher (P < .01), and prothrombin time on day 1 was more prolonged (P < .01) in the chemotherapy group. No significant difference was seen between groups in intraoperative data, morbidity, or duration of hospitalization. Histologic examination of adjacent non-neoplastic liver confirmed mild to severe fatty degeneration in 91% of the patients undergoing neoadjuvant chemotherapy, compared with 53% in those without neoadjuvant chemotherapy (P = .023). Although the number of neoplasms in chemotherapy patients was greater than that of the other group, overall and disease-free survival rates were comparable between groups. CONCLUSIONS: Despite mild postoperative liver dysfunction, pre-resection hepatic arterial chemotherapy did not increase morbidity.     

Treatment strategy for multiple hepatic metastases of colorectal carcinoma

We describe the treatment strategy for multiple hepatic metastases of colorectal carcinoma based on a review of the literature and our own results. Although a number of studies have suggested that multiplicity or bilobar distribution of metastases is associated with poor outcome, liver resection is thought to be the only potentially curative treatment. The only contraindications to surgery are the presence of extrahepatic metastases (with the exception of resectable lung metastases) and if radical removal of all detectable tumors is not possible. Hepatectomy should be performed with the aim of maintaining a delicate balance between radical removal of tumors and the preservation of as much residual hepatic mass as possible with minimal blood loss. Surgeons should be familiar with the use of intraoperative ultrasonography, a standard adjunct to liver resection. Preoperative portal vein embolization may be indicated in selected patients as a means of inducing hypertrophy in the remaining hepatic parenchyma. Received for publication on Aug. 30, 1998; accepted on Nov. 2, 1998     

Effectiveness of prehepatectomy intra-arterial chemotherapy for multiple bilobar colorectal cancer metastases to the liver: a clinicopathologic study of peritumoral vasculobiliary invasion

BACKGROUND: Consensus remains to be achieved concerning prehepatectomy neoadjuvant chemotherapy as a treatment strategy for multiple bilobar colorectal liver metastases, in part because the effect of prehepatectomy neoadjuvant chemotherapy has not been determined pathologically. We investigated the efficacy of prehepatectomy intra-arterial chemotherapy for multiple bilobar colorectal cancer metastases to the liver. METHODS: Clinicopathologic data for 37 consecutive patients with > or =5 bilobar liver metastases from colorectal cancer who underwent hepatectomy were analyzed retrospectively with respect to long-term outcome and histological findings in resected liver tumors. RESULTS: In the 15 patients receiving neodadjuvant chemotherapy (NEO+ group), liver metastases progressed in 2 patients, remained stable in 8 patients, responded more than 50% in 4 patients, and responded completely in 1 patient (combined response rate, 33.3%). Overall and hepatic recurrence-free survival tended to be higher in responders than in nonresponders ( P = .053). Microscopic invasion of the portal vein, hepatic vein, and bile ducts near liver tumors was less frequent according to use of neoadjuvant chemotherapy and responsiveness to the therapy (responders, 20.0%; patients not receiving neoadjuvant therapy [NEO-], 72.7%; P < .05). Such microscopic invasion independently predicted hepatic recurrence by multivariate analysis ( P = .011). CONCLUSIONS: A neoadjuvant chemotherapy-associated decrease in microscopic vasculobiliary invasion by metastatic liver tumors was related to clinical response and favorable outcome.     

Surgical treatment of liver metastases from colorectal carcinoma

In patients with colorectal liver metastases, hepatic resection is the treatment of choice, and the 5-year overall survival rate after surgery is now approaching 60%. The multidisciplinary and multimodality approaches that may include preoperative systemic chemotherapy, and the recent innovative surgical techniques that may include complex ultrasound guided hepatic resection, have enabled a large proportion of patients to undergo potentially curative treatment. The definition of resectability has shifted from a focus on tumor characteristics, such as tumor number and size, to determination whether both intrahepatic and extrahepatic disease can be completely resected, and whether such an approach is appropriate from an oncological standpoint. Hepatobiliary surgeons and medical oncologists should work together to evaluate patients with colorectal liver metastases to individualize the treatment strategy to maximize the chances of long-term survival.     

新辅助化疗提高不可切除结直肠癌肝转移手术切除率

一、概述 结直肠癌是最常见的恶性肿瘤之一,全世界新发病例约100万／年,每年约50万患者因此而死亡。死亡的主要原因是肝转移。肝脏是结直肠癌最常见的,也常常是唯一的转移部位。而结直肠癌诊断时约有10％～25％发现时已伴有肝转移（同时性肝转移）,还有50％～70％最终发展到肝转移,尸检发现结直肠癌肝转移率高达60％～71％。结直肠癌肝转移完全切除后,5年生存期为21％～48％,甚至治愈。     

Neoadjuvant chemotherapy and resection of advanced synchronous liver metastases before treatment of the colorectal primary

BACKGROUND: In many patients with advanced synchronous liver metastases from colorectal tumours, the metastases progress during treatment of the primary, precluding curative treatment. The authors have investigated a management strategy that involves high-impact chemotherapy first, resection of liver metastases second and finally removal of the primary tumour in patients with adverse prognostic factors. METHODS: Twenty consecutive patients with non-obstructive colonic (nine patients) or rectal (11 patients) cancer and advanced synchronous liver metastases were treated according to this strategy. Median age was 56 years. Patients received between two and six cycles of 5-fluorouracil, oxaliplatin and irinotecan-based chemotherapy. Data were collected prospectively. RESULTS: Overall survival rates at 1, 2, 3 and 4 years after the start of treatment were 85, 79, 71 and 56 per cent respectively, with a median survival of 46 months. Sixteen of the 20 patients had complete removal of liver metastases and colorectal tumours (resectability rate 80 per cent). CONCLUSION: This new strategy produced resectability and survival rates better than those expected from the published data on patients with disease of similar severity. It allows initial control and downstaging of liver metastases, and delivery of preoperative radiotherapy for rectal cancer without the fear that liver metastases will meanwhile progress beyond the possibility of cure.     

Combined portal vein embolization and neoadjuvant chemotherapy as a treatment strategy for resectable hepatic colorectal metastases

OBJECTIVES: The objectives of this study are 1) to determine whether the future liver remnant will grow after portal vein embolization (PVE) in patients with colon cancer on concurrent chemotherapy and 2) to determine whether recovery after extended hepatectomy is improved after PVE. PURPOSE: Neoadjuvant chemotherapy followed by hepatic resection is an increasingly used therapeutic strategy for curative treatment for colorectal metastases. However, such chemotherapy may result in steatosis, liver damage, and compromised liver regeneration and recovery. This study aims to determine whether PVE can be used during neoadjuvant therapy to enhance growth of future residual liver and to improve postoperative recovery. METHODS: From September 1999 to September 2004, 100 patients with colorectal metastases to the liver were subjected to PVE as preparation for extended hepatic resection, 43 of whom were embolized during neoadjuvant chemotherapy. Liver growth was examined by computed tomography volumetric analysis. Clinical outcomes of the 71 patients subsequently resected were compared with 100 consecutive patients subjected to extended resection without PVE (controls). RESULTS: After a median wait of 30 +/- 2 days after PVE, patients on neoadjuvant chemotherapy experienced a median contralateral (nonembolized) liver growth of 22% +/- 3% compared with 26% +/- 3% for those without chemotherapy (P = NS). The number of patients with <5% growth was also similar: 4 of 43 versus 6 of 57 (P = NS). Comparison of patients resected after PVE to a simultaneous cohort of 100 consecutive patients subjected to extended resection without prior PVE demonstrated a lower fresh frozen plasma requirement (P = 0.01), a lower peak bilirubin (P = 0.002), and a shorter length of stay (P = 0.03). Mortality was similar (0% vs. 2%). CONCLUSIONS: Liver growth occurs after PVE even when cytotoxic chemotherapy is administered. No major complications occurred with PVE. Patients requiring major hepatic resection should be considered for PVE during neoadjuvant chemotherapy to improve subsequent recovery after resection.     

Two-stage hepatectomy procedure to treat initially unresectable multiple bilobar colorectal liver metastases: technical aspects

A two-stage hepatectomy procedure is a therapeutic strategy for patients presenting with initially unresectable multiple and bilobar colorectal liver metastases in order to achieve a curative R0 resection. The main goal of this approach is to minimize the risk of postoperative liver failure resulting from a too small remnant liver after completing a curative resection. This procedure combines two sequential liver resections that involve perioperative chemotherapy and portal vein embolization. This article describes our standardized strategy of two-stage hepatectomy combined with portal vein embolization used over the last 15 years and discusses the alternative procedures as well as their respective advantages and drawbacks.     

术中超声辅助肝切除联合射频消融根治性治疗双叶弥散性结直肠癌肝转移

目的 探索术中超声辅助下肝切除联合射频消融根治性治疗双叶弥散性结直肠癌肝转移的安全性和可行性.方法 2006年1月至2012年1月期间,5例被2名以上专家判断失去手术时机的双叶弥散性结直肠癌肝转移患者,成功实施根治性治疗.其中男2例,女3例.平均年龄57岁 (44～65岁).回顾性分析其手术相关临床指标.结果 术中超声发现肝脏转移病灶平均20.4个 (15～28个),围手术期死亡0例,肝功能衰竭0例.围手术并发症:腹腔感染1例,大量腹水2例,胸腔积液4例.术后1个月影像学检查和血清CEA等证实达到根治性治疗.结论 术中超声辅助下一期肝切除联合射频消融治疗是双叶弥散性结直肠癌肝转移治疗的一种很好的选择,可以提高转移性肝癌的切除率.