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不可切除的结直肠癌肝转移患者的肝移植——病例报告

Liver transplantation in a patient with unresectable colorectal liver metastases -- a case report.

作者信息

Hrehoreţ D, Alexandrescu S, Braşoveanu V, Grigorie R, Zielinski C, Popescu I

出版信息

Chirurgia (Bucur). 2013 Sep-Oct;108(5):719-24.

Abstract

BACKGROUND

Due to the lower survival rates achieved, in the early period of liver transplantation era, in patients with colorectal liver metastases, and because of the organ shortage,in the last two decades colorectal liver metastases are considered a contraindication for liver transplantation. However, the increasing number of marginal donors, and the improvements in posttransplant immunossuppresion, chemotherapy and methods to assess the extrahepatic disseminationof colorectal cancer, opened the perspective of liver transplantation to certain patients with malignancies (such as HCC beyond Milan criteria, and selected patients with cholangiocarcinomaor liver metastases from neuroendocrine tumors).Since some of these patients experienced favorable outcomes,in the last years, there were authors that considered a rationalerevisitation of the benefits of liver transplantation in patients with unresectable colorectal liver metastases. Thus, in 2006, a Norwegian group started a study which aims to assess the results of liver transplantation in patients with unresectable colorect alliver metastases. Their results were unexpectedly favorable, revealing that 5-year overall survival rate was 60%, and the quality of life was excellent in the first year following transplantation.However, all the patients presented relapse of the disease in the first two years following transplantation. In the present paper we present the clinico-pathologic characteristics,the pre- and postoperative management and the outcome of a patient with unresectable colorectal liver metastases who underwent liver transplantation in a very advanced state of the disease (when he developed subacute liver failure due to insufficient functional liver parenchyma and toxicity of chemotherapy).We consider useful to present such observations,because collecting the data presented by different centers maybe contributive to identification of a selected group of patients who could benefit from liver transplantation.

CASE REPORT

A 42-year old male patient, it was diagnosed with upper rectum cancer and multiple bilobar liver metastases in April 2009. Chemotherapy was started (in another hospital),and because the disease was stable after 7 cycles of FOLFOX and Bevacizumab, the patient was reffered to surgery (for a "two stage" liver resection). In October 2009 it was performed primary tumor resection associated with left lateral section ectomy and segment 4 metastasectomy. Because in November 2009 CT scan re-evaluation revealed progression of liver metastases, the second stage hepatectomy was precluded. Subsequent therapy consisted in radio embolization, multiple lines of chemotherapy,and targeted therapies. After more than 2 years, the liver metastases progressed and the patient developed progressive cholestatic subacute liver failure due to insufficient functional liver parenchyma and chemotherapy toxicity. In this state of the disease, he was admitted in our hospital, being dependant by liver dialysis and plasma exchange procedures. Due to the patients' age, and because the MDCT scan revealed the absence of extrahepatic disease (after almost three years of disease progression), and he could not benefited from any type of antineoplastic treatment due to progressive cholestatic subacute liver failure, liver transplantation with an organ from amarginal donor was considered and performed in January 2012.The postoperative course was uneventful, and the quality of his life improved (being fully reinserted social and professional).The immunosuppressive regimen consisted in Sirolimus and Mycophenolate mofetil, and the adjuvant chemotherapy started two months following liver transplantation. However,the patient developed extrahepatic relapse of the disease (lung metastases and retroperitoneal recurrence), but now, at morethan 20 months following transplantation, he is still alive in agood clinical condition.

CONCLUSIONS

In patients with multiple unresectable liver onlycolorectal metastases, liver transplantation may improve overallsurvival and quality of life, by using marginal grafts whichcannot be allocated to the patients with standard indicationsfor liver transplantation. The advent of MDCT and PET CT scan and the use of m-TOR inhibitors may improve the resultsachieved by liver transplantation in patients with CLMs.Further studies could be useful in an attempt to disclosewhether a selected group of patients with unresectable liveronly colorectal metastases could become acceptable candidatesfor liver transplantation.

摘要

背景

在肝移植时代早期,由于结直肠癌肝转移患者的生存率较低,且存在器官短缺问题,在过去二十年中,结直肠癌肝转移被视为肝移植的禁忌证。然而,边缘供体数量的增加、移植后免疫抑制、化疗以及评估结直肠癌肝外播散方法的改进,为某些恶性肿瘤患者(如超出米兰标准的肝癌、部分胆管癌患者或神经内分泌肿瘤肝转移患者)开辟了肝移植的前景。由于其中一些患者取得了良好的治疗效果,近年来,有作者认为有必要重新审视肝移植对不可切除的结直肠癌肝转移患者的益处。因此,2006年,一个挪威研究小组启动了一项研究,旨在评估肝移植治疗不可切除的结直肠癌肝转移患者的效果。他们的结果出人意料地令人满意,显示5年总生存率为60%,移植后第一年生活质量极佳。然而,所有患者在移植后的头两年内均出现疾病复发。在本文中,我们介绍了一名处于疾病晚期(因功能性肝实质不足和化疗毒性发展为亚急性肝衰竭)接受肝移植的不可切除的结直肠癌肝转移患者的临床病理特征、术前和术后管理及治疗结果。我们认为展示此类观察结果很有用,因为收集不同中心提供的数据可能有助于确定一组可能从肝移植中获益的特定患者群体。

病例报告

一名42岁男性患者,2009年4月被诊断为上段直肠癌伴双叶多发肝转移。开始化疗(在另一家医院),由于经过7个周期的FOLFOX和贝伐单抗治疗后疾病稳定,患者转诊至外科手术(进行“两阶段”肝切除术)。2009年10月进行了原发肿瘤切除并联合左外叶切除及4段转移瘤切除。由于2009年11月CT扫描重新评估显示肝转移进展,二期肝切除术未能进行。后续治疗包括放射性栓塞、多线化疗及靶向治疗。两年多后,肝转移进展,患者因功能性肝实质不足和化疗毒性发展为进行性胆汁淤积性亚急性肝衰竭。在这种疾病状态下,他入住我院,依赖肝透析和血浆置换治疗。由于患者年龄因素,且MDCT扫描显示无肝外疾病(经过近三年疾病进展),且由于进行性胆汁淤积性亚急性肝衰竭无法从任何类型的抗肿瘤治疗中获益,2012年1月考虑并实施了使用边缘供体器官的肝移植手术。术后过程顺利,他的生活质量得到改善(完全重新融入社会和职业生活)。免疫抑制方案包括西罗莫司和霉酚酸酯,肝移植术后两个月开始辅助化疗。然而,患者出现了疾病的肝外复发(肺转移和腹膜后复发),但目前,在移植后20多个月,他仍存活且临床状况良好。

结论

对于仅有不可切除的肝转移的结直肠癌患者,肝移植可通过使用无法分配给有肝移植标准适应证患者的边缘供肝来提高总生存率和生活质量。MDCT和PET CT扫描的出现以及m-TOR抑制剂的使用可能会改善肝移植治疗结直肠癌肝转移患者的效果。进一步的研究可能有助于确定一组仅有不可切除的肝转移的结直肠癌患者是否能成为肝移植的合适候选者。

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