Chemotherapy for the conversion of unresectable colorectal cancer liver metastases to resection

Resection of colorectal liver metastases (CLM) is the ultimate aim of treatment strategies in most patients with liver-confined metastatic colorectal cancer. Long-term survival is possible in selected patients with initially resectable or unresectable CLM. As a majority of patients have unresectable liver disease at the outset, there is a clear role for chemotherapy to downstage liver disease making resection possible. Studies of systemic chemotherapy with or without biologic therapy in patients with unresectable CLM have resulted in increased response rates, liver resection rates and survival. A sound physiologic rationale exists for the use of hepatic arterial infusion (HAI) therapy. Studies have shown that HAI with floxuridine combined with systemic chemotherapy increases response rates and liver resection rates in those patients with initially unresectable CLM. Toxicity from preoperative chemotherapy, biologic therapy and HAI therapy may adversely affect hepatic resection but can be kept minimal with appropriate monitoring. All conversion strategies should be decided by a multidisciplinary team.     

Cryosurgery for colorectal liver metastases

Destructive therapy for liver tumors has been available for some time and a number of options have been used. These include alcohol injection, heating therapy with laser and, more recently, radiofrequency ablation and cryosurgery. The principle of cryosurgery is to destroy tissue by freezing and causing expansion of intracellular water. The effect of this treatment is to cause disruption of the cell membrane as the ice expands, thereby killing the cells and, secondly, releasing intracellular antigen into the circulation to promote an immune response. Lastly, there is a "frostbite" effect with thrombophlebitis of vessels feeding the tumor because of the freezing. A number of trials have evaluated destructive therapy, but none have shown definite benefit over chemotherapy alone. This review examines the data as it currently stands.     

Cell kinetics of colorectal liver metastases

PURPOSE: Liver metastases are the main cause of death in patients with colorectal cancer. We defined the proliferative activity of a metastatic liver cell population to investigate its potential role as an indicator of clinical outcome in patients with metastatic disease of the colorectum. METHODS: The S-phase cell fraction, evaluated asin vitro [³H]thymidine-labeling index, was determined on liver metastases of primary colorectal cancers from 75 patients. RESULTS: Cell proliferation was not related to the degree of liver involvement, the site of the primary cancer, or the time of presentation of liver metastases. Survival at 2 years was statistically different for patients with slowly proliferating (78 percent) or rapidly proliferating liver metastases (47 percent) (P=0.024). The risk of death for patients with high [³H]thymidine-labeling index lesions was consistently threefold that of patients with low [³H]thymidine-labeling index lesions throughout the observation period. Bivariate analysis showed that cell proliferation was a further prognostic discriminant within the subsets characterized by a different degree of liver involvement. CONCLUSIONS: These results indicate that cell proliferation is a good prognostic marker even in patients with liver metastases from colorectal cancer. The clinical implications of the marker could be further potentiated by considering it in association with some clinical aspects of known prognostic relevance.     

Multi-modality treatment of colorectal liver metastases

Liver metastases synchronously or metachronously occur in approximately 50% of colorectal cancer patients. Multimodality comprehensive treatment is the best therapeutic strategy for these patients. However, the optimal pattern of multimodality therapy is still controversial, and it raises several significant concerns. Liver resection is the most important treatment for colorectal liver metastases. The definition of resectability has shifted to focus on the completion of R0 resection and normal liver function maintenance. The role of neoadjuvant and adjuvant chemotherapy still needs to be clarified. The management of either progression or complete remission during neoadjuvant chemotherapy is challenging. The optimal sequencing of surgery and chemotherapy in synchronous colorectal liver metastases patients is still unclear. Conversional chemotherapy, portal vein embolization, two-stage resection, and tumor ablation are effective approaches to improve resectability for initially unresectable patients. Several technical issues and concerns related to these methods need to be further explored. For patients with definitely unresectable liver disease, the necessity of resecting the primary tumor is still debatable, and evaluating and predicting the efficacy of targeted therapy deserve further investigation. This review discusses different patterns and important concerns of multidisciplinary treatment of colorectal liver metastases.     

Cell kinetics of colorectal liver metastases

PURPOSE: Liver metastases are the main cause of death in patients with colorectal cancer. We defined the proliferative activity of a metastatic liver cell population to investigate its potential role as an indicator of clinical outcome in patients with metastatic disease of the colorectum. METHODS: The S-phase cell fraction, evaluated asin vitro [³H]thymidine-labeling index, was determined on liver metastases of primary colorectal cancers from 75 patients. RESULTS: Cell proliferation was not related to the degree of liver involvement, the site of the primary cancer, or the time of presentation of liver metastases. Survival at 2 years was statistically different for patients with slowly proliferating (78 percent) or rapidly proliferating liver metastases (47 percent) (P=0.024). The risk of death for patients with high [³H]thymidine-labeling index lesions was consistently threefold that of patients with low [³H]thymidine-labeling index lesions throughout the observation period. Bivariate analysis showed that cell proliferation was a further prognostic discriminant within the subsets characterized by a different degree of liver involvement. CONCLUSIONS: These results indicate that cell proliferation is a good prognostic marker even in patients with liver metastases from colorectal cancer. The clinical implications of the marker could be further potentiated by considering it in association with some clinical aspects of known prognostic relevance.Supported by the Associazione Italiana Ricerca Cancro, Milan, Italy.     

Imaging diagnosis of colorectal liver metastases

Rapid advances in imaging technology have improvedthe detection,characterization and staging of colorec-tal liver metastases. Multi-modality imaging approachis usually the more useful in diagnosis colorectal livermetastases. It is well established that hepatic resection improves the long-term prognosis of many patientswith liver metastases. However,incomplete resectiondoes not prolong survival,so knowledge of the exactextent of intra-hepatic disease is crucially important indetermining patient management an...     

Chemotherapy and repeat resection abrogate the prognostic value of neutrophil lymphocyte ratio in colorectal liver metastases

BackgroundEvolution in surgical and oncological management of CRLM has called into question the utility of clinical risk scores. We sought to establish if neutrophil lymphocyte ratio (NLR) has a prognostic role in this patient cohort.MethodsFrom 2005 to 2015,379 hepatectomies were performed for CRLM, 322 underwent index hepatectomy, 57 s hepatectomies were performed. Clinicopathological data were obtained from a prospectively maintained database. Variables associated with longterm survival following index and second hepatectomy were identified by Cox regression analyses and reviewed along with 30-day post-operative morbidity and mortality.ResultsFollowing index hepatectomy 1-,3-and 5-year survival was 90.7%, 68.1% and 48.6%. Major resection, positive margins and >5 tumours were negatively associated with survival. Those with elevated NLR(>5) had a median survival of 55 months, compared to 70 months with lower NLR(p = 0.027). Following neoadjuvant chemotherapy, no association between NLR and survival was demonstrated (p = 0.93). Furthermore, NLR >5 had no impact on prognosis following repeat hepatectomy. Tumour diameter >5 cm (p = 0.04) was the sole predictor of poorer survival (p = 0.049).ConclusionDespite elevated NLR correlating with shorter survival following index hepatectomy, this effect is negated by neoadjuvant chemotherapy and second hepatectomy for recurrent disease. This data would not support the use of NLR in the preoperative decision algorithm for patients with CRLM.     

Current treatment for colorectal liver metastases

Surgical resection offers the best opportunity for survival in patients with colorectal cancer metastatic to the liver,with five-year survival rates up to 58% in selected cases.However,only a minority are resectable at the time of diagnosis.Continuous research in this field aims at increasing the percentage of patients eligible for resection,refining the indications and contraindications for surgery,and improving overall survival.The use of surgical innovations,such as staged resection,portal vein embolizat...     

Repeated procedures for colorectal liver metastases

BACKGROUND/AIMS: After primary liver surgery a recurrence of colorectal liver metastases (CRLM) occurs in 45-80% of patients. Without the possibility of further surgical treatment, most of these patients die within 1 year. The aim of this study was to evaluate the long-term results of repeated liver procedures for recurrent CRLM. METHODOLOGY: The authors operated on a total of 151 patients with CRLM from January 1, 2000 to November 1, 2005. Repeated procedures were performed on 24 patients in the interval 6-37 months after primary liver surgery. A total of 51 procedures were performed. Long-term results were compared with the group of patients (N = 127) where only one type of liver procedure was performed. RESULTS: 30-day postoperative mortality (N = 24) was zero. 83.3%, 64.8% and 34.3% of patients survived 1.2 and 3 years after the repeated procedures. Disease-free interval (DFI) was 32.1%, 5.3% and 0% for 1, 2 and 3 years. 30-day postoperative mortality (N = 127) was 0.8%. 76.6%, 51.9%, 31.9% survived 1, 2 and 3 years after the liver procedures (p < 0.08). DFI in this group of patients for 1, 2 and 3 years was 57.9%, 35.1% and 17.7% (p < 0.0001). CONCLUSIONS: Repeated liver procedures are fully indicated. They significantly prolong the life of patients with CRLM recurrence.     

Extensive resections for colorectal liver metastases

Journal of Hepato-Biliary-Pancreatic Sciences - Mortality and morbidity rates after liver resections have decreased with better surgical techniques and perioperative care. The aim of this study was...     

Management of liver metastases from colorectal cancer

About 50% of colorectal cancer patients develop liver metastasis, and liver resection is considered the only curative therapy. However, the rate of recurrence is high, which contributes to poor prognosis. Since surgical resection coverage has increased because of improved hepatectomy including portal vein embolization, tumors shrink because of the effectiveness of recent chemotherapy, such as FOLFOX and FOLFIRI, and it has become possible for many patients whose cancer was judged unresectable before to undergo resection. Improvement of new anticancer drugs such as molecularly targeted biologics is greatly changing therapeutic systems of metastatic colorectal cancer, and it is time for us to innovate stage IV therapy. In this report, we will review new treatment strategies for metastatic liver cancer from colorectal cancer, clinical trials of new anticancer drugs for liver metastasis, surgery and ablation as local therapy, and further clarify complex therapeutic systems for metastatic liver tumors from colorectal cancer.     

Resection of liver metastases from colorectal cancer

PURPOSE: This study was undertaken to determine the indications for and value of liver resection for metastases from colorectal cancer. METHODS: From 1978 through 1991, 66 patients were operated on for liver metastases from colorectal cancer. All patients had had a curative resection of their colorectal cancer. Forty resections of the liver were major anatomic resections. RESULTS: Five patients died in the postoperative period. All resections were intended to be curative, but in 16 of the patients the resection became noncurative. None of these patients lived more than two years after liver resection. Fifty patients with a curative resection had a three-year survival rate of 36 percent, postoperative death included. Recurrence in the liver was observed in 30 patients (60 percent) from 3 to 33 (median, 11) months after the liver resection. Four patients had repeated resections performed. Two of them are alive without recurrences 34 and 60 months after the first liver resection, respectively. The difference in survival between curative and noncurative liver resection was highly significant (P=0.01). CONCLUSIONS: Sex, age, Dukes stage of primary colorectal cancer, synchronous or metachronous appearance of metastases, or number of metastases could not predict long-term prognosis. The only factors of predictive value were tumor size less than 4 cm in diameter, a free resection margin, and no extrahepatic tumor. If it is possible to do a curative resection, there should be few contraindications against liver surgery as it is the only treatment that can demonstrate long-term survival for approximately one-third of the patients, and it is the only possibility of a cure.     

Treatment of liver metastases from colorectal cancer

In recent years several new local as well as systemic treatment options have become available for patients with advanced colorectal cancer. A survey among Dutch hospitals revealed considerable differences in the use of diagnostic and therapeutic strategies. Radiofrequency ablation is a promising technique that is currently being investigated in a randomised trial. The role of adjuvant chemotherapy in patients with resectable liver metastases and of neoadjuvant chemotherapy in patients with nonresectable liver metastases has not been clearly established yet. The current status of local and systemic treatment options for colorectal cancer liver metastases is reviewed.     

同时性结直肠癌肝转移患者的生存分析

目的分析结直肠癌合并同时性肝转移患者的生存状况和相关影响因素。 方法回顾性分析2000年至2010年复旦大学附属中山医院收治的1061例结直肠癌合并同时性肝转移患者的病例。收集所有患者的临床资料、病理特征、治疗策略、住院费用、随访状况等,进行生存状况分析,并采用单因素和Cox比例风险回归模型等分析影响结直肠癌肝转移生存的相关因素。 结果肝转移灶可切除患者中,同期切除肠道原发灶和肝转移灶与分期切除患者的住院费用分别为25693元、34129元(P<0.05),手术并发症(分别为24.5%、20.5%)和总生存期方面(分别为48.5月、47.0月)无显著差异。肝转移灶不可切除且原发灶无症状的患者中,原发灶切除的患者总体中位生存时间明显好于原发灶未切除的患者(分别为19.0月、9.3月,P<0.001)。肠道原发灶分化Ⅲ～Ⅳ级、肝转移灶≥4个、最大肝转移灶直径≥5 cm、肝外转移、肠道原发灶未手术切除和肝转移灶非手术治疗是影响肠癌同时性肝转移患者预后的独立危险因素。将上述6个危险因素各设定为1分,所有患者分为低风险组(0～1分)、中风险组(2～3分)和高风险组(4～6分),5年存活率分别为51%、16%和0%(P<0.001)。 结论结直肠癌合并同时性肝转移患者中,原发灶和转移灶均可切除的可予以同期切除,原发灶可切除且无出血梗阻症状的不可切除的肝转移仍建议在合适时机切除肠道原发灶。根据上述6个独立预后因素所建立的预测模型可以指导临床采取合适的治疗方案。     

一期切除结直肠癌并发肝转移癌的临床应用

目的探讨结直肠癌肝转移一期切除临床应用的安全性和可行性。方法 2008年7月至2013年2月在我院诊治的结直肠癌并发肝转移癌患者72例,被随机分为对照组和治疗组各36例,对照组给予分期切除,治疗组给予一期切除。结果在围手术指标的比较中,治疗组和对照组术中出血量分别为[(487.38±100.87)m L和(644.39±124.88)m L,P0.05],术后下床活动时间分别为[(6.00±2.75)d和(9.50±3.00)d,P0.05],术后住院时间分别为[(14.25±2.95)d和(18.85±4.66),P0.05];在并发症发生情况的比较中,36例治疗组未发生切口感染,显著低于对照组(8.3%,P0.05);在生存情况的对比中,治疗组和对照组的中位生存时间分别为[(47.44±6.44)月和(34.98±5.29)月,P0.05],1a生存率分别为97.2%和80.6%(P0.05)。结论一期切除结直肠癌和肝转移癌是安全可行的,能有效促进患者康复,减少术后并发症,从而使患者生存获益。     

Hepatic arterial chemotherapy for colorectal liver metastases

The management of hepatic metastasis from colorectal cancer represents a significant clinical problem. For the majority of patients with colorectal liver metastases, chemotherapy will be the mainstay of treatment. Considerable data now exists to support hepatic arterial chemotherapy as being effective over systemic chemotherapy both in terms of quality of life and response rates. Morbidity and mortality rates are reduced when catheters are placed by skilled dedicated surgeons using rigorous protocols.     

The argument for liver resection in colorectal liver metastases

The first liver resection for colorectal metastasis was performed by Cattell in 1940. Unfortunately, there has never been a randomized control trial for liver resection against other treatment modalities (best supportive care, palliative chemotherapy, etc). Since this operation is now well established in the surgical repertoire, it would now be ethically difficult to undertake such a trial.