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。     

Importance of response to neoadjuvant chemotherapy in patients undergoing resection of synchronous colorectal liver metastases

The purpose of this study was to compare the treatment and outcome in patients referred for staged re section of synchronous colorectal liver metastases. The records of patients who had undergone colon or rectal resection and were then referred for evaluation of clinically resectable synchronous liver metastases between January 1995 and January 2000 were reviewed. Comparisons were made between patients who did not receive neoadjuvant chemotherapy and had exploratory operations after recovery from colon re section and patients who did receive chemotherapy before liver resection. A total of 106 patients were treated during the 5-year period. Neoadjuvant chemotherapy was given to 52 of the patients; in 29 of them the disease did not progress, but in 17 patients the disease progressed while they were receiving treatment. Median follow-up was 30 months. Patient- and tumor-related variables were similar between groups. Five-year survival was statistically similar between patients who did and those who did not receive neoadjuvant chemotherapy (43% vs. 35%, P = 0.49). Patients within the neoadjuvant group whose dis ease did not progress while they were receiving chemotherapy experienced significantly improved sur vival as compared to patients who did not receive chemotherapy (85% vs. 35%, P = 0.03). In the setting of synchronous colorectal liver metastases, the response to neoadjuvant chemotherapy may be a prognos tic indicator of survival and may assist in the selection of patients for conventional or experimental adju vant therapies. Presented at the Forty-Third Annual Meeting of The Society for Surgery of the Alimentary Tract, San Francisco, California, May 19–22, 2002 (oral presentation).     

Resection of nonresectable liver metastases from colorectal cancer after neoadjuvant chemotherapy.

OBJECTIVE: The authors discuss the technique and evaluate the results of an aggressive surgical approach in patients with primarily unresectable colorectal liver metastases that were downstaged by chronomodulated chemotherapy. BACKGROUND: Resection is the best treatment of colorectal liver metastases, but it may be achieved in only 10% of patients. In the remaining 90%, survival is poor, even after partial response to chemotherapy. Little is known about the results of curative hepatectomy in patients whose metastases are downstaged by chemotherapy. PATIENTS AND METHODS: Fifty-three patients with colorectal liver metastases initially unresectable because of ill located (8), large (8), multinodular (24) lesions, or because of extrahepatic disease (13) were downstaged by a systemic chronomodulated chemotherapy associating 5-fluorouracil, folinic acid and Oxaliplatin to the point that operation could be performed. This consisted of a major hepatectomy in 37 patients and a minor resection in 16. Associated procedures (including 5 two-stage hepatectomies and 3 pulmonary resections) were performed in 25 patients. RESULTS: There was no operative mortality. Complications occurred in 14 patients. The cumulative 3- and 5-year survival rates were 54% and 40% (according to the type of lesions: ill-located, 75% and 48%; large, 62% and 62%; multinodular, 54% and 40%; extrahepatic, 43% and 14%). Hepatic recurrence (34 patients, 64%) was amenable to repeat surgery in 15 cases. CONCLUSIONS: Liver resection may be achieved in some previously unresectable patients with the help of an effective chemotherapy. The benefit in survival seems comparable to that obtained with primary liver resection (40% at 5 years). This therapeutic strategy involves a multimodal approach, including repeat hepatectomies and extrahepatic surgery.     

Clinical risk scores in the current era of neoadjuvant chemotherapy for colorectal liver metastases

Background

Clinical risk scores (CRS) within the context of neoadjuvant chemotherapy for colorectal liver metastases (CRLM) has not been validated. The predictive value of clinical risk scoring in patients administered neoadjuvant chemotherapy prior to liver surgery for CRLM is evaluated.

Methods

A prospective database over a 15‐year period (April 1999 to March 2014) was analysed. We identified two groups: A, neoadjuvant chemotherapy prior to CRLM surgery; and B, no neoadjuvant chemotherapy.

Results

Overall median survival in groups A and B were 36 (2–137) months and 33 (2–137) months. In group A, nodal status, size, number of metastases and carcinoembryonic antigen levels were not found to be independent predictors of overall survival (OS). However, patients with a shorter disease‐free interval of less than 12 months had an increased OS (P = 0.0001). Multivariate analysis of high‐ and low‐risk scores compared against survival in group B (P < 0.05) confirms the applicability of the scoring system in traditional settings.

Conclusion

Traditional CRS are not a prognostic predictive tool when applied to patients receiving neoadjuvant chemotherapy for CRLM. Disease‐free interval may be one independent variable for use in future risk score systems specifically developed for the neoadjuvant chemotherapy era.     

Neoadjuvant chemotherapy as a treatment strategy for multiple bilobar liver metastases from colorectal carcinoma

Hepatic resection remains the only potentially curative therapy for patients with colorectal liver metastases. Because most have multiple bilobar liver metastases, surgical resection is possible in only 25-58% of patients with colorectal liver metastases. Currently, attention is focused on the potential for neoadjuvant chemotherapy to render formerly unresectable patients resectable. The availability of more efficacious chemotherapy agents and an inventive approach to delivery schedules have resulted in an increase in the number of candidates for hepatic resection after neoadjuvant chemotherapy. Although tumor response varies with regimen and/or route of chemotherapy for colorectal liver metastases, with 16-63% tumor response rates, hepatic resection for responders after neoadjuvant chemotherapy gives survival benefits, with 20-48% 5-year survival rates after surgery. Provided that neoadjuvant chemotherapy controls multiple bilobar liver metastases well, aggressive hepatic resection should be considered for patients with those lesions. As a treatment strategy for multiple bilobar liver metastases, neoadjuvant chemotherapy is a useful to increase resection rates and may contribute to the improvement of prognosis in patients with such lesions.     

Intra-arterial chemotherapy in the treatment of liver metastases of colorectal cancer]

AIM: The authors evaluate the value of hepatic intrarterial chemotherapy (HAC) as an alternative treatment for hepatic metastases from colo-rectum cancer unsuited to radical surgery. METHODS: This study evaluates the physiopathological and pharmacodynamic bases for this type of treatment, the correct procedure for patient staging and selection, the surgical technique used to insert the infusional system, surgical complications and those linked to endoarterial treatment, the evaluation of response and the results. Complications correlated to the infusional system were evaluated in a total of 1223 patients in 10 non-randomised studies and 7 randomised studies taken from the literature. Complications correlated to chemotherapy were analysed in a total of 777 patients from 8 randomised studies and 7 randomised using FUDR. Special emphasis was placed on the possible association of locoregional and systemic treatment in order to prevent extrahepatic progression, the main cause of death in patients undergoing a single cycle of HAC. RESULTS: By comparing locoregional and systemic treatment taken from a number of randomised and non-randomised studies, the results were evaluated in terms of objective response and survival. CONCLUSIONS: There was no proportional increase in survival rates compared to systemic treatment only, in spite of the large proportion of objective responses achieved using locoregional treatment alone.     

Inversion of the sequence of surgery after neoadjuvant chemotherapy for synchronous liver metastases from colorectal cancer

In some patients with colorectal cancer and synchronous liver metastases, chemotherapy and current combinations of chemotherapy allow the size of these metastases to be reduced so that they can be surgically resected. However, in many patients, the initial systematic treatment of the primary tumor is associated with growth of the metastases (which predict the patient's life expectancy). This metastatic growth contraindicates surgical treatment that might otherwise be curative. We report the case of a patient with advanced recto-colonic cancer, which responded well to chemotherapy given as neoadjuvant treatment prior to surgery, in which the hepatic metastases were resected before excision of the primary tumor.     

Regional and systemic chemotherapy for colorectal metastases to the liver

The fluoropyrimidines 5-FU and FUDR are antimetabolites that have limited activity in the treatment of patients with colorectal metastases. The availability of implantable or portable drug infusion pumps has caused a renewed interest in continuous infusion therapy using these drugs for patients with colorectal metastases to the liver. While the search for new, more effective agents or combinations continues, it is reasonable to evaluate dose schedules and drug combinations that would maximize the effectiveness of these fluoropyrimidines and lower their toxicity in investigational protocols. In most series both drugs have higher response rates, less myelosuppression, but greater liver toxicity when given by continuous intraarterial infusions compared to bolus injections given intravenously. Nevertheless, there is still insufficient data to conclude that survival rates are sufficiently prolonged in patients for whom an implantable drug infusion pump has been used for regional FUDR chemotherapy. On the other hand, symptomatic patients may have sufficient palliation to constitute an identifiable group for whom this approach is justified. Results of several randomized prospective studies addressing the efficacy of regional versus systemic FUDR chemotherapy infusions will be available in the near future. If these demonstrate improved survival for patients receiving regional FUDR chemotherapy, it will be appropriate to consider this approach in selected patient settings. Until such data are available, routine use of this approach in asymptomatic patients is not warranted.

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Resumen Las fluoropirimidinas 5-FU y FUDR son antimetabolitos de limitada actividad en el tratamiento de pacientes con metástasis colorrectales. La disponibilidad de bombas implantables a portátiles de infusión ha causado renovado interés en la terapia por infusión continua de estas drogas en pacientes con metástasis hepáticas de cáncer calorrectal. En tanto que continúa la búsqueda de nuevos y más efectivos agentes o combinaciones de agentes, aparece razonable la valoración de las dosis y de las combinaciones de las drogas para lograr la máxima efectividad de las fluoropirimidinas y rebajar su toxicidad en protocolos de investigación. En la mayoría de las series ambas drogas exhiben mayores tasas de respuesta y menor mielosupresión, pero más toxicidad hepática, cuando se administran por infusión intraarterial continua en comparación con inyección de bolos. Sin embargo, todavía los datos son insuficientes para llegar a la conclusión de que las tasas de superviviencia resultan suficientemente prolongadas en los pacientes sometidos a quimioterapia con FUDR por infusión con bomba implantable. Por otra parte, los pacientes sintomáticos pueden recibir suficiente paliación como para constituir un grupo identificable para el cual este enfoque está justificado. Pronto estarán disponibles los resultados de varios estudios prospectivos y aleatorizados orientados a determinar la eficacia de la quimioterapia regional versus sistémica, con FUDR. Si éstos demuestran mejoría en la supervivencia de pacientes que reciben quimioterapia regional con FUDR, será apropiado considerar este aproche en situaciones clínicas seleccionadas. Hasta que tales datos estén disponibles no se justifica el uso rutinario de este método en pacientes asintomáticos.

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Résumé Les fluoropyrimidines 5-FU et FUDR sont des antimétabolites qui ont une action limitée dans le traitement des malades porteurs de métastases colo-rectales. La possibilité de disposer de pompes implantables ou portables pour infuser des drogues est à l'origine d'un renouveau d'interêt pour l'injection continue d'agents antimitotiques susceptibles d'agir contre les métastases hépatiques des cancers colo-rectaux. Pendant que la recherche de nouveaux agents se poursuit, il est raisonnable d'apprécier les doses et les combinaisons de drogues qui devraient augmenter l'efficacité des fluoropyrimidines et diminuer leur toxicité en ayant recours à de nouveaux protocoles. Dans la majorité des séries, les 2 drogues sont plus actives, exercent une action moins marquée sur la moelle, mais leur toxicité sur le foie est plus grande, lorsqu'elles sont administrées par infusion intra-artérielle continue au lieu d'être administrées par injection discontinue. A ce jour, les données recueillies chez les malades porteurs d'une pompe implantable permettant la chimiothérapie régionale par le FUDR sont insuffisantes pour conclure que la durée de la survie est prolongée. Par ailleurs, les malades qui présentent des troubles symptomatiques peuvent bénéficier d'un répit qui justifie cette méthode renouvelée de traitement. Les résultats de plusieurs études prospectives randomisées concernant l'efficacité de la chimiothérapie régionale avec le FUDR par rapport à la chimiothérapie générale seront rapidement disponibles. Si ces résultats se montrent favorables la méthode pourra s'appliquer à des malades sélectionnés. Pour le moment et jusqu'à la conclusion de ces études, l'emploi systématique de la méthode chez les malades qui accusent des troubles n'est pas justifié.

     

新辅助化疗治疗初始可切除结直肠癌肝转移效果的Meta分析

目的通过对使用新辅助化疗后行手术治疗和单纯手术治疗的初始可切除的结直肠癌肝转移（CRLM）患者进行Meta分析,以评价新辅助化疗治疗初始可切除CRLM的效果。 方法检索PubMed、Cochrane Library、Embase、中国知网、万方数据库2006年1月至2021年1月收录的关于接受新辅助化疗后行手术治疗（新辅助化疗组）和单纯手术（单纯手术组）治疗初始可切除的CRLM患者的相关文献。采用RevMan 5.4软件处理数据并进行荟萃分析。 结果共纳入12篇文献6 644例患者,其中新辅助化疗组3 348例,单纯手术组3 296例。单纯手术组3年无病生存率优于新辅助化疗组（OR=0.57,95% CI：0.48~0.68,P<0.001）,手术时间更短（WMD=13,95% CI：12.78~13.22,P<0.001）。而两组并发症发生率、肝内复发率、住院时间、5年总生存率的比较,差异无统计学意义。 结论初始可切除的CRLM患者接受新辅助化疗是安全的,但长期获益并不明显。临床风险评分不失为一种好的策略,对于存在高复发风险的CRLM患者,行新辅助化疗可能延长生存时间。     

Concepts in the prevention and treatment of liver metastases of colorectal cancer by regional chemotherapy

Three different treatments of regional chemotherapy in colo-rectal malignancies and their results are presented. 1. Prophylactic chemotherapy with 5-FU--via the recanalized umbilical vein in patients without liver metastases (randomized study since 10/1980). 2. Intraportal adjuvant chemotherapy after resection of liver metastases. 3. Intraarterial chemotherapy in patients with unresectable liver metastases. The regional chemotherapy of the liver in colo-rectal diseases seems to increase the survival rate and the quality of life. The Port-A-Cath-system can be used repeatedly, however, there is a certain rate of complications to be expected.     

结直肠癌肝转移的规范化治疗

结直肠癌发病率逐年升高,超过50％的患者会发生肝转移.随着治疗理念的不断发展以及治疗水平的提高,结直肠癌肝转移目前被认为是潜在可治愈性疾病,其预后也有了显著改善.但是,如何选择治疗方法的问题也随之产生.对于结直肠癌肝转移的规范化治疗,应该包括影像学检查,治疗方式的选择以及多学科团队(MDT)诊断治疗等多个方面,同时应该针对患者制订个体化治疗方案.笔者就结直肠癌肝转移影像学检查方式的选择,不同治疗方法的疗效比较,肝转移灶的外科治疗以及MDT诊断治疗模式等内容进行讨论.     

Surgical treatment of colorectal liver metastases

Resection is the only curative treatment of colorectal liver metastases proofed by a long-term follow-up. The operation is indicated if the metastases are completely removable with sufficient liver parenchyma remaining after resection and if the patient is fit for surgery. The resection is not indicated in cases with non resectable extrahepatic tumours and lymph node metastases distal the hepatoduodenal ligament. The postoperative mortality amounts to about 5 % and the 5-year-survival-rates range between 20 and 40 % depending on the selection of patients. Aims of new concepts of operative therapy are the improvement of resectability by preoperative portal vein embolization, the resection combined with local destructive methods and preoperative chemotherapy. Additionally, new drugs for adjuvant treatment after resection of metastases are studied. The interdisciplinary discussion of the course before and after therapy is essential for the individual optimal treatment.