经皮冷冻治疗结直肠癌肝转移

背景：结直肠癌肝转移的手术切除率低,其他疗法效果亦欠佳。目的：探讨经皮冷冻治疗结直肠癌肝转移的疗效和安全性。方法：于超声或CT引导下,对326例不能手术切除的结直肠癌肝转移患者行经皮冷冻治疗,术后定期随访。结果：326例患者共接受526次经皮冷冻治疗。治疗后3个月,基线CEA水平升高者中77．6％降至正常范围。280例接受CT随访者中,冷冻病灶完全反应（CR）者14．6％,部分反应（PR）41．1％,稳定（SD）24.3％,进展（PD）20．0％。中位随访期为36食月（7—62个月）,复发率为41．7％。全部病例中位存活期为29个月（3～62个月）。治疗后第1、2、3、4、5年存活率分别为78％、62％、41％、34％和23％：肿瘤直径≤3cm、肝右叶肿瘤、冷冻前CEA≤10μg／L、冷冻后原先升高的CEA降至正常、冷冻治疗2～3次和冷冻后行经导管肝动脉化学栓塞（TACE）治疗者存活率较高。严重并发症发生率为5．2％。结论：经皮冷冻治疗结直肠癌肝转移安全、有效,可作为肿瘤不能手术切除者的替代治疗手段。     

Radiofrequency Ablation of Liver Metastases from Colorectal Cancer: A Literature Review

Liver metastases occur in up to 60% of patients with colorectal cancer, and the control of liver metastases is considered to be of primary importance because it is a critical factor in determining prognosis. Radiofrequency ablation (RFA) therapy is one of the least invasive techniques for unresectable hepatic malignancies and can be performed safely using percutaneous, laparoscopic, or open surgical techniques. The local tumor progression rates after RFA for colorectal liver metastases range from 8.8% to 40.0%, and 5-year survival rates range from 20.0% to 48.5%. No prospective, randomized trials comparing the efficacy of RFA with that of surgical resection for colorectal liver metastases are currently available. However, some retrospective studies have reported that patients who received RFA had a survival rate similar to that observed in surgically treated groups, while other studies have reported better survival among patients who underwent surgical resection. The use of a laparoscopic or open surgical approach allows the repeated placement of RFA electrodes at multiple sites to ablate larger tumors. An accurate evaluation of treatment response is very important for the success of RFA therapy because a sufficient safety margin (at least 0.5 cm) can prevent local tumor progression. This review critically summarizes the current status of RFA for liver metastases from colorectal cancer.     

结直肠癌同时性肝转移患者原发灶切除的预后分析

目的 原发灶切除能否使结直肠癌肝转移患者生存获益,目前仍有争议.本研究探讨接受原发灶切除结直肠癌肝转移患者的生存状况及预后的影响因素.方法 回顾性分析2010年1月～2018年2月在国家癌症中心/中国医学科学院肿瘤医院治疗的371例结直肠癌同时性肝转移患者的病例资料.根据治疗方式分为单纯化疗组和原发灶切除组,分析两组患...     

结直肠癌肝转移的综合治疗策略

结直肠癌(colorectal cancer,CRC)是世界上常见的消化道肿瘤之一,约有50%的患者最终出现肝转移。对于发生肝转移的患者,若不经治疗,中位生存期仅为6.9个月,5年生存率为0。若肝脏转移灶行根治性手术,则中位生存期为35个月,5年生存率为30～50%,因此手术切除仍是结直肠癌肝转移治疗的首选。对于同时性肝转移的患者,若无肠道梗阻、穿孔、出血等症状,笔者倾向于同时性切除原发灶和转移灶,术中联合应用B超探查、微波、射频等新技术来提高切除率,降低复发率。而临床上只有少部分患者(10%～15%)可以行手术治疗。对于不可切除的肝转移灶,需通过多学科讨论,针对疾病某一时期,制定出详细的个体化综合性治疗方案,如术前新辅助化疗、联合靶向药物治疗、门静脉栓塞术的应用、局部治疗、放疗等,使得一些不可切除的病灶转化为可切除病灶。因此癌肿作为一项全身性疾病,单纯依靠一种治疗手段很难取得理想的效果,需要多学科的合作,通过对疾病的不同时期进行认识、讨论,以便找到针对某一时间段疾病的最佳治疗方法。同时术后需要定期复查及时发现复发和转移以及制定进一步治疗计划,从而提高患者的长期生存率及生活质量。     

Liver metastases from colorectal cancer: present surgical approach

BACKGROUND/AIMS: New developments in surgical techniques and strategies are modifying the indications to resection of liver metastases. METHODOLOGY: From January 1986 to December 2000, 246 consecutive patients with colorectal liver metastases underwent curative hepatic resection. Surgical strategies included simultaneous resection of primary and metastatic colorectal tumor, re-resection of colorectal liver recurrences, two-stage resection and resection of the inferior vena cava when involved by the tumor. Disease-free survival in relation to clinical, pathological and surgical factors was retrospectively assessed with univariate and multivariate analyses. RESULTS: The overall operative mortality was 0.8%. The 1-, 3- and 5-year disease-free survival rates were 75%, 47% and 40%, respectively. Tumors larger than 7 centimeters, multiple lesions, tumors involving more than 2 segments and those requiring major hepatectomy had a worse prognosis at univariate analysis. A size of the tumor above 7 centimeters was the only independent prognostic factors at multivariate analysis. Two-stage and inferior vena cava resection increased operability; re-resection of recurrent colorectal secondaries prolonged survival. CONCLUSIONS: Resection of colorectal liver metastases is safe and effective; it should be considered the treatment of choice for this disease and proposed even for advanced lesions. Counseling of the hepatobilary surgeon should be asked for once a liver secondary is detected in the preoperative work-up of a colorectal cancer.     

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。     

Percutaneous cryosurgery for the treatment of hepatic colorectal metastases

AIM：To determine the safety and efficacy of efficacy of percutaneous cryosurgery for treatment of patients with hepatic colorectal metastases.
METHODS： Three hundred and twenty-six patients with non-resectable hepatic colorectal metastases underwent percutaneous cryosurgery under the guidance of ultrasound or CT. Follow-up was 1 mo after cryosurgery and then every 4 mo thereafter by assessment of tumor markers, liver ultrasonography, and abdominal CT. For lesions suspicious of recurrence, a liver biopsy was performed and subsequent repeat cryosurgery was given if histology was positive for cancer.
RESULTS： All patients underwent a total of 526 procedures of cryosurgery. There were 151 patients who underwent repeat procedures of cryosurgery for recurrent tumors in the liver and extrahepatic places. At 3 mo after cryosurgery, carcinoembryonic antigen （CEA） levels in 197 （77.5%） patients who had elevated markers before cryosurgery decreased to normal range. Among 280 patients who received CT following-up, cryotreated lesions showed complete response （CR） in 41 patients （14.6%）, partial response （PR） in 115 patients （41.1%）, stable disease （SD） in 68 patients （24.3%） and progressive disease （PD） in 56 patients （20%）. The recurrence rate was 47.2% during a median follow-up of 32 mo （range, 7-61）. Sixty one percent of the recurrences were seen in liver only and 13.9% in liver and extrahepatic areas. The recurrence rate at cryotreated site was only 6.4% for all cases. During a median follow-up of 36 mo （7-62 mo）, the median survival of all patient was 29 mo （range 3-62 mo）. Overall survival was 78%, 62%, 41%, 34% and 23% at 1, 2, 3, 4 and 5 years, respectively, after the treatment. Patients with tumor size less than 3 cm, tumor in right lobe of liver, lower CEA levels （〈 100 ng/dL） and post- cryosurgery TACE had higher survival rate. There wasno significant difference in terms of survival based on the number of tumors, pre-cryosurgery chemotherapy and t     

Locoregional therapy for liver metastases from colorectal cancer: the possibilities of intraarterial chemotherapy, and new hepatic-directed modalities

Liver metastasis of colorectal cancer is a life-threatening prognostic factor. Hepatic resection, when possible, is the best therapeutic modality, although the overall survival rate is still low (30%). The diagnosis has been carried out by clinical examination, abnormal alkaline phosphatase, lactic acid dehydrogenase and tumor markers, abdominal liver echography and computed tomography scan. Angiography and intraoperative echography are useful for resection. The number of hepatic metastases and the surgical margin are probably the most significant prognostic factors. Colorectal cancer may spread predominantly to the liver making regional treatment strategies viable options. Subtotal hepatic resections and segmentectomies are potentially curable procedures for single or small numbers of hepatic metastases without other sites of disease. However, there have been no prospective randomized trials comparing patients with unresected liver metastases and resected metastases. Regional chemotherapy with floxuridine seems useful combined with hepatic resection or as palliative therapy. Gastric ulcer and biliary sclerosis are the main related toxicities. Patients with localized, unresectable hepatic metastases or concomitant bad medical condition may be candidates for radiation, percutaneous ethanol injection, cryosurgery, radiofrequency, hypoxic flow-stop perfusions with bioreductive alkylating agents, hepatic arterial ligation, embolization and chemoembolization. These new hepatic-directed modalities of treatment are being investigated and may offer new approaches to providing palliation and prolonging survival. This review reports the possibilities of intraarterial chemotherapy and other novel hepatic directed approaches to the treatment of liver metastases from this common disease.     

Neoadjuvant and adjuvant therapy in relation to surgery for colorectal liver metastases

Liver resection is associated with prolonged survival in patients with colorectal liver metastases. At diagnosis, 15-20% of patients have resectable colorectal liver metastases whereas other patients have too advanced disease to enable surgical treatment and receive chemotherapy. In patients undergoing resection of colorectal liver metastases, disease relapse occurs in up to 70%. Therefore, a combined approach including preoperative or postoperative chemotherapy or both has been tested to improve outcome after surgery. In patients with unresectable colorectal liver metastases, chemotherapy is initially the sole treatment option. The considerable improvement of the efficacy of anticancer agents has contributed to increase the response rate in patients with advanced colorectal cancer. In case of major response to chemotherapy, surgery with curative intent can be offered to patients with initially unresectable liver metastases.     

Factors affecting the prognosis of anatomical liver resection for liver metastases from colorectal cancer

BACKGROUND/AIMS: Liver resection has improved the survival of colorectal cancer patients with metastases. However, there are groups at high risk of recurrence after liver resection. This report reviews our results using anatomical liver resection and analyzes the prognostic factors. METHODOLOGY: We analyzed 78 patients who underwent anatomical liver resection of liver metastases from colorectal cancer between June 1988 and March 2002. RESULTS: Twenty-nine patients had synchronous metastases, and 49 had metachronous. The 5-year overall survival rate was 43%. Patients with more than three metastatic tumors had a significantly poorer 5-year recurrence-free survival rate. There was no statistical difference in the 5-year overall survival rate between patients with metachronous metastases (41%) and those with synchronous (44%) metastases. The 5-year overall survival rate was significantly poorer for patients with an interval of 1 year or less between colorectal and liver resections than for patients with a longer interval. Recurrence after liver resection occurred in 38 patients (49%). The recurrences occurred in the lung in 18 patients, in remnant liver in 15 patients, in lymph nodes in 7 patients, and in other organs in 6 patients. CONCLUSIONS: We conclude that anatomical liver resection of liver metastases from colorectal cancer improves survival. Liver metastases that occur within 1 year of colorectal resection may need an interval of observation before liver resection.     

The role of surgery in the treatment of liver metastases for colorectal cancer patients.

BACKGROUND/AIMS: Liver metastases deriving from colorectal cancer can be treated with curative intention in a select number of patients. Controversy does, however, persist pertaining to the impact of adjuvant treatment strategies. The aim of this study is to elucidate upon the various treatment modalities for patients suffering from liver metastases of colorectal primary tumor as well as to provide a rationale for surgical and adjuvant treatment. METHODOLOGY: From November 1987 to September 1998, a total of 449 consecutive patients suffering from liver metastases deriving from a colorectal cancer were documented at our institution in a prolective study. Prognostic factors providing the most beneficial outcome (whether with surgical and/or adjuvant treatment modalities) were analyzed by univariate and multivariate analysis. RESULTS: Whenever possible, curative (R0) surgical resection of colorectal liver metastases provides the most benefit to the patient. Multivariate analysis revealed tumor infiltration of the lymph nodes of the hepatoduodenal ligament and metachronous occurrence of liver metastases as most independent factors related to survival. CONCLUSIONS: Adjuvant post-operative chemotherapy fails to significantly improve survival following resection of liver metastases when compared to the liver resection only group. In patients with unresectable metastases, regional arterial chemotherapy did not improve survival significantly when compared with systemic chemotherapy.     

Liver resection or cryotherapy for colorectal liver metastases

Background and aims While there is promising survival data for cryosurgery of colorectal liver metastases, local recurrence following cryoablation remains a problem. We aimed to compare morbidity and mortality, as well as the recurrence pattern and survival after liver resection and cryotherapy (alone or in combination with resection) for liver metastases.Patients and methods Between 1996 and 2002, 168 patients underwent liver resection alone and 55 patients had cryotherapy (25 in combination with liver resection) for colorectal liver metastases. The patient, tumour and operative details were recorded prospectively and the two patient groups were compared regarding morbidity, survival and recurrence.Results More patients had a prior liver resection, liver metastases were smaller and less frequently synchronous, morbidity was significantly lower and hepatic recurrence was significantly more frequent in the cryotherapy group. Five-year survival rates following resection and cryotherapy were comparable (23 and 26% respectively), while overall and hepatic recurrence-free survival was inferior following cryotherapy.Conclusion Cryotherapy is a valuable treatment option for some patients with non-resectable colorectal liver metastases. While survival is comparable to that after resection, higher hepatic recurrence rates following cryotherapy should caution against the use of cryotherapy for resectable disease until the results of randomized controlled trials are available.     

Surgical management of recurrence after resection of colorectal liver metastases

The optimal treatment for recurrent lesions after hepatectomy for colorectal liver metastases is controversial. We report the outcome of aggressive surgery for recurrent disease after the initial hepatectomy and the influence on quality of life of such treatment. Forty-five (70%) of the 64 surviving patients developed recurrence after the initial hepatectomy for liver metastases. The determinants of hepatic recurrence were the distribution and the number of liver metastases. Twenty-eight (62%) of patients with recurrence underwent resection. A second hepatectomy was performed in 20 patients, and a third hepatectomy was done in 5 patients. Ten patients with pulmonary metastasis underwent partial lung resection on 14 occasions, while resection of brain metastases was performed in 3 patients on 5 occasions. There were no operative deaths after resection of recurrent disease. The morbidity rate was 28% after repeat hepatectomy, 21% after pulmonary resection, and 0% after resection of brain metastasis. The Karnofsky performance status (PS) after the last surgery was not significantly different from that after the initial hepatectomy. The 3- and 5-year survival rates after the second hepatectomy were 54% and 14%, respectively. The 3-and 5-year survival rates of the patients undergoing resection of extrahepatic recurrence were both 17%. The survival rate after resection of recurrent disease (n=28) was significantly better than that of patients (n=17) with unresectable recurrence (P < 0.05). For the 66 patients with colorectal liver metastases, the 5-year survival rate after initial hepatectomy was 50%. The distribution and the number of liver metastases and the presence of extrahepatic disease, as single factors, significantly affected prognosis after the initial hepatectomy. Multivariate analysis revealed that only the presence of extrahepatic metastasis and a disease-free interval of less than 6 months were independent predictors of survival after the initial and second hepatectomy, respectively. It is concluded that aggressive surgery is an effective strategy for selected patients with recurrence after initial hepatectomy. Careful selection of candidates for repeat surgery will yield increased clinical benefit, including long-term survival.     

Resection and local therapy for liver metastases

In 30-50% of patients the liver is a preferred site of distant disease for many malignant tumours. Due to the high incidence, most of the available data relate to metastases arising from colorectal primaries. Surgical resection is at present the only treatment offering potential cure. The achievable 5-year survival rate is 30%. However, only 10-15% of patients with colorectal liver metastases can undergo potentially curative liver resection. Therefore, accurate staging is an important prerequisite in selecting patients who would benefit from surgery. Recurrence of hepatic metastases after potentially curative resection occurs in up to 60% of the cases. Results demonstrate that re-resection of liver metastases can provide long-term survival rates in a carefully selected group of patients without extrahepatic disease. Because of the high rate of recurrences following an apparently curative resection several authors investigated the use of adjuvant chemotherapy (systemic, intraportal, and hepatic arterial infusion). Until recently none had shown effectiveness. Pre-operative chemotherapy seems to be a promising approach in patients with liver metastases initially considered unsuitable for radical surgery. Recently, neoadjuvant chemotherapy has been proposed as an alternative approach to conventional surgery as initial management with the aim of improving the results in resectable liver metastases. Interventional strategies (ethanol injection, cryosurgery, laser-induced thermotherapy, radio-frequency ablation) and combined modalities (surgical/interventional) are additive methods which may help to improve treatment results in the future.     

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.     

外科治疗策略对结直肠癌同时性肝转移患者预后改善的影响

目的化疗及外科治疗策略的优化使结直肠癌肝转移患者生存期得到了明显改善。本研究拟利用中国国家癌症中心数据库数据评价同时性结直肠癌肝转移患者的生存率变化以及探讨其与治疗策略之间的关系。方法回顾性分析2010年1月~2018年2月在国家癌症中心/中国医学科学院肿瘤医院诊治的结直肠癌同时性肝转移患者临床资料,按确诊年度,分为2010~2011年、2012~2013年、2014~2015年、2016~2017年四组,比较其肿瘤特异性生存时间及外科治疗策的差异。结果本研究共纳入1286例患者,中位生存时间从2010~2011年度的20个月提高到2016~2017年度的33个月。3年肿瘤特异性生存率从23.0%提高到45.3%。5年肿瘤特异性生存率从9.5%提高到35.2%。接受原发灶切除和肝转移灶局部治疗患者生存优于单纯化疗组、单纯原发灶切除组和肝转移灶局部治疗组。结论基于人群的研究显示同时性结直肠癌肝转移患者整体生存得到显著改善。在接受化疗的同时,患者接受外科治疗策略比例的增高与生存率升高有关。     

Surgical treatment of malignant liver tumours

Surgical resection is the mainstay of treatment for malignant liver tumours and offers the only chance of cure. Advances in radiological imaging, surgical technique and peri-operative management have enabled liver resection to be performed safely. Partial hepatectomy is indicated for the treatment of hepatocellular carcinoma and hepatic metastases from colorectal cancer. In addition, it may be utilized for selected patients with liver metastases from other primary tumours. Total hepatectomy with transplantation may be of benefit in some patients with unresectable neuroendocrine metastases or small hepatocellular carcinomas. The role of cryosurgery has not been precisely defined, and it needs to be compared with other palliative therapies such as ethanol injection and hepatic artery embolization.     

Prognostic factors following liver resection for hepatic metastases from colorectal cancer

AIM: To determine the impact of prognostic factors on survival of patients with metastases from colorectal cancer that underwent liver resection. METHODS: The records of 28 patients that underwent liver resection for metastases from colorectal cancer between April 1992 and September 2001 were retrospectively analyzed. Thirty-eight resections were performed (more than one resection in eight patients and two patients underwent re-resections). The primary tumor was resected in all the patients. A screening protocol for liver metastases including clinical examinations every three months, ultrassonography and CEA level until 5 years of follow-up and after every 6 months, was applied. The prognostic factors analyzed regarding the impact on survival were: Dukes C stage of primary tumor, size of metastasis >5 cm, a disease-free interval from primary tumor to metastasis < 1 year, CEA level > 100 ng/mL, resection margins < 1 cm and extrahepatic disease. The Kaplan-Meier curves, log rank and Cox regression were used for the statistical analysis. RESULTS: Perioperative morbidity and mortality were 39.3% and 3.6%, respectively. The 5-year survival rate was 35%. The independent prognostic factors were: disease-free interval from primary tumor to metastasis < 1 year and extrahepatic disease. CONCLUSIONS: The liver resection for metastases from colorectal cancer is a safe procedure with more than 30% 5-year survival. Disease-free interval from primary tumor to metastasis < 1 year and extrahepatic disease were independent prognostic factors.     

An update on chemotherapy of colorectal liver metastases

Surgical resection of liver metastases of colorectal cancer greatly improves the clinical outcome of patients with advanced disease. Developments in chemotherapeutic agents and strategies bring hope of a cure to patients with initially unresectable colorectal liver metastases (CLM). Perioperative chemotherapy significantly improves the survival time of patients who receive curative-intent hepatectomy. Even for unresectable CLM, recent studies demonstrated that active preoperative chemotherapy could achieve shrinkage of liver metastasis and thus render some for resection. Furthermore, an increase in tumor resection rate and prolonged survival time among patients with CLM has been observed following the application of monoclonal antibodies in recent years. However, the value of chemotherapy via hepatic arterial infusion is still unclear. More trials should be conducted in patients with CLM in order to improve survival.     

An update and our experience with metastatic liver disease

Metastatic liver disease remains a challenging and life-threatening clinical situation with an obscure and dismal prognosis and outcome. The liver is the most common site of metastatic spread of colorectal cancer and nearly half of the patients with colorectal cancer ultimately develop liver metastasis during the course of their diseases. Death from colorectal cancer is often a result of liver metastases. Over half of these patients die from their metastatic liver diseases. At the time of diagnosis, hepatic metastases are present in 15-25% of patients, and another 25-50% will develop metachronous liver metastases within 3 years following resection of the primary tumor. Over the last decade, there have been tremendous advances in the treatment of metastatic liver disease. Hepatic resection still remains the gold standard for the treatment of metastatic lesions which are amenable to surgery. Unfortunately, up to 40 percent of patients are identified as having additional disease at the time of exploration, and 20 percent are found to be unresectable. Regional therapies such as radiofrequency ablation, microwave ablation and cryotherapy may be offered to patients with isolated unresectable metastases. Other options like hepatic artery chemotherapy and chemoembolization, portal vein embolization and immunotherapy also play a vital role in management of metastatic liver disease when used in combination with other therapies. This article reviews the history of metastatic liver disease, epidemiology, diagnosis and various treatment modalities available for liver metastases along with our experience in management of advance metastatic liver disease.