不可切除结直肠癌肝转移的转化性治疗策略

手术是治疗结直肠癌肝转移最有效的也是惟一有可能治愈的手段,但是大多数结直肠癌肝转移病人并不能够行肝转移灶切除手术。近些年,用各种细胞毒药物和（或）靶向药物等使不可切除的肝转移病灶缩小,转化为可切除,继而行手术切除,从而获得治愈的可能。转化性治疗的目的是获得最佳反应率,而不是获得最大反应率。术前转化性化疗应选择高效化疗方案,并尽量缩短疗程。具体方案选择方面,KRAS野生型病人推荐西妥昔单抗联合FOLFOX/FOLFIRI,其中5-氟尿嘧啶持续给药,而KRAS突变型病人考虑贝伐珠单抗联合两药化疗或者三药化疗方案。在行转化性治疗时,一旦转移灶转化为可切除,应积极手术切除。     

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肝脏是结直肠癌最常见的转移部位,手术切除是惟一可能治愈的方法,通过积极的转化治疗可以使一部分不可切除的肝转移病灶转化为可切除,并获得良好的生存。基于转化治疗后肝切除预后与转化治疗的线数、疗程等有关,多程化疗后带来的肝脏毒性及术后并发症增加等情况,建议在高强度、高效化疗适当疗程后,肿瘤退缩至符合可切除标准即可。关于最佳手术方式、同期肝转移原发灶与转移灶处理先后顺序问题,目前没有定论,建议由多学科综合治疗团队根据具体情况制定个体化的治疗方案。     

结直肠癌肝转移外科治疗的争议

肝脏是结直肠癌最常见的转移部位,肝转移是结直肠癌治疗失败的主要原因。外科切除在结直肠癌肝转移综合治疗模式中占据主导地位．也是患者获得治愈机会的重要手段。尽管如此,在结直肠癌肝转移外科治疗领域目前还存在很多困惑和争议．包括结直肠癌肝转移分期系统尚不完善、潜在可切除标准尚未统一、可切除肝转移灶是否需要新辅助化疗、根治切除后辅助化疗方案的选择以及不可切除肝转移灶患者无症状原发灶的处理等。本文依据近年来发表的研究资料,结合自身临床实践,剖析肝转移外科研究领域中不同的观点和依据。     

结直肠癌同时性肝转移手术时机的选择

目的 探讨可切除性结直肠癌同时性肝转移的手术时机.方法 回顾性分析2009年10月至2011年11月上海交通大学医学院附属仁济医院收治的5例结直肠癌伴同时性肝转移患者的临床资料,根据患者的情况分别行手术治疗+辅助化疗、新辅助化疗或靶向治疗.结果5例患者均行手术+术后辅助治疗.3例原发灶和肝转移灶可切除者,1例先行新辅助化疗,肝转移灶明显缩小后一期手术切除原发灶和肝转移灶,术后6个月MRI检查发现肝内复发;1例未行新辅助化疗,术后9个月CT检查发现肺内多发转移灶;1例因原发灶穿孔腹腔感染,先切除原发灶,术后化疗+靶向治疗,二期切除肝内转移灶,术后12个月CT检查发现肺内单发转移灶.其余2例因肝内多发性转移灶无法手术切除,仅切除原发灶,1例术后13个月死于骨转移;另1例行辅助化疗+靶向治疗,CT检查示肝内转移灶曾一度进行性缩小,但术后11个月开始肝内转移灶渐增多、增大.5例患者术后均行k-ras基因检测,除病例2的Condon 12位点为野生型、Condon 13位点为突变型外,其余患者均为野生型.结论新辅助化疗或新辅助化疗+靶向治疗的效果个体差异大,消灭体内微转移灶作用有限,首选一期手术切除原发灶和同时性肝转移灶有可能使患者获益最大.     

结直肠癌肝转移转化治疗的研究进展

结直肠癌患者在全病程中发生肝转移的概率达40%~50%,肝转移是影响结直肠癌患者长期预后的重要不利因素。手术切除肝转移灶是唯一可能达到近似根治效果的治疗选择。对于判断为不可切除的肝转移灶,经过综合治疗,使肿瘤缩小,进而将初始不可切除病灶转化为可切除病灶,称为转化治疗。转化治疗可分为以化疗±靶向为主的系统治疗及局部治疗。本文重点综述近年来结直肠癌肝转移转化治疗相关研究成果:(1)梳理肝转移癌手术可切除性评估标准;(2)探讨疗效评估、手术时机及肿瘤侧性对转化治疗方案选择的影响等临床问题;(3)总结转化治疗方案新进展,包括经典双药方案、三药联合的加强方案、分子靶向药物、免疫检查点抑制剂、多种局部疗法以及门静脉栓塞/两步肝切除、联合肝脏分割和门静脉结扎的分步肝切除术在转化治疗中的应用效果。本综述通过分析结直肠癌肝转移转化治疗现有问题,以期为结直肠癌肝转移的临床治疗发展提供参考。     

结直肠癌伴不可切除的同时性肝转移的腹腔镜治疗

目的:探讨结直肠癌伴有同时性不可切除肝转移灶的腹腔镜治疗的可行性及临床应用价值。方法:回顾分析2011年6月至2012年12月31例结直肠癌伴不可切除的同时性肝转移患者的临床资料及随访结果。按原发灶手术切除方式分为两组,A组行开腹手术切除结直肠癌原发灶(n=18),B组行腹腔镜手术(n=13)。术后均采取mFOLFOX6方案化疗。对比分析两组患者手术时间、术中出血量、术后排气时间、术后住院时间、术后接受首次化疗时间及治疗效果。结果:31例均成功施行结直肠癌切除术,腹腔镜组无一例中转开腹及严重并发症发生。术后患者行mFOLFOX6方案化疗至少2个周期。经统计学分析发现,两组患者手术时间、治疗效果差异无统计学意义(P>0.05),但腹腔镜组术中出血量明显减少(P<0.01),术后排气时间明显缩短(P<0.05),术后住院时间明显减少(P<0.05),术后接受首次化疗的时间明显缩短(P<0.05)。结论:对于不可切除的同时性结直肠癌肝转移患者,行腹腔镜原发肿瘤切除是安全、可行的;与开腹手术相比,腹腔镜手术治疗结直肠癌伴不可切除的同时性肝转移,在切除原发灶的手术中具有出血量少、创伤小、术后肠功能恢复快、住院时间明显缩短并促进术后早期化疗等优势。腹腔镜手术对原发肿瘤及转移灶的治疗效果与开腹手术无明显差别,具有良好的临床应用价值。     

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结直肠癌肝转移发生率高,且临床就诊者大多数肝转移灶为不可切除。尽管关于不可切除结直肠癌肝转移病人原发灶的处理尚有一定争议,但随着结直肠癌原发灶处理经验的积累,多学科综合治疗团队(MDT)模式的开展,转化性治疗思维的应用,"个体化治疗"原则的实施,针对不可切除结直肠癌肝转移病人原发灶的处理逐步形成包括手术切除原发灶在内较合理的综合治疗体系。手术切除、新辅助治疗与姑息治疗的合理选择是改善不可切除结直肠癌肝转移病人生存质量及提高生存期,获得最佳治疗效果的关键。     

大肠癌肝转移术前化疗后的最佳手术时机

化疗联合手术治疗已逐渐成为结直肠癌肝转移病人的标准治疗方式。对于可切除的大肠癌肝转移病人是否需要术前化疗仍存在争议。存在预后不良因素时应接受术前化疗,术前化疗不应＞6周期。不可切除的肝转移病人均应接受术前化疗,术前化疗后定期复查,如转化为可切除,应立即切除。一般认为,停用化疗4周后可以手术切除肝转移灶,但如果联合贝伐单抗,应在停止治疗6~8周后进行手术。     

结直肠癌同时性肝转移治疗46例分析

目的:探讨结直肠癌同时性肝转移的有效治疗方法。方法:对1996～2004年收治的46例结直肠癌同时性肝转移的临床资料和随访资料进行回顾性分析。根据治疗方法的不同分为3组:A组21例,为一期切除原发灶和肝转移灶并经肝动脉和门静脉置泵化疗者;B组15例,为单纯原发灶切除并经肝动脉和门静脉置泵化疗者;C组10例,为原发灶和肝转移灶均未能切除而仅行肝动脉和门静脉置泵化疗者。用KaplanMeier法对病人的生存时间作统计分析。结果:A、B、C3组术后中位生存期分别为38、20和13个月;各组之间术后生存时间的比较均有显著统计学差异(P<0.01)。结论:结直肠癌原发灶和肝转移灶一期手术切除并经肝动脉和门静脉置泵化疗的疗效最好;肝转移灶无法切除者能将原发灶切除并经肝动脉和门静脉置泵化疗也可取得较好的疗效;原发灶和肝转移灶未能切除而仅经肝动脉和门静脉置泵化疗的疗效相对较差。对结直肠癌同时性肝转移应采取以手术切除为主的综合措施进行积极治疗。     

结直肠癌肝转移的转化治疗

对结直肠癌肝转移来说,手术是惟一的治愈手段。但80%的病人初始是不可切除的,将不可切除肝转移转化为可切除是提高结直肠癌总体存活率的关键。目前常用的转化手段有全身化疗（包括单纯化疗、化疗联合靶向药物等）、肝动脉灌注（HAI）、射频消融（RFA）、联合门静脉结扎或栓塞的分期肝切除、联合肝脏分隔及门静脉结扎的二步肝切除等。了解各种转化治疗的有效率和适应证是选择合适治疗的前提。     

客观评价和正确开展结直肠癌的新辅助治疗

结直肠癌的新辅助治疗应遵循以下原则：（1）对于II期,III期的直肠癌病人应进行术前新辅助治疗。具体方案可采用放疗或放化疗联合。但不推荐单纯化疗。（2）对于不伴有远处转移的结肠癌病人不推荐术前新辅助治疗。仅对于可切除结肠癌肝转移病人可行新辅助化疗,以达缩小病灶,杀灭潜在转移灶之目的。     

中国肝癌肝移植临床实践指南（2014版）

肝移植是被全世界认可的治疗终末期肝病的有效手段之一.目前,肝移植在全国范围内已得到广泛开展,亟待相关临床实践指南来指导全国肝移植工作更规范、有效、安全地开展.中华医学会器官移植学分会、中华医学会外科学分会移植学组及中国医师协会器官移植医师分会组织专家制订了《中国肝癌肝移植临床实践指南（2014版）》,重点阐述肝移植受者选择标准、术前降期治疗、受者抗病毒治疗、受者免疫抑制剂应用、术后肿瘤复发的防治5部分内容.米兰标准是肝癌肝移植受者选择的参考基准,而杭州标准是对米兰标准局限于肿瘤形态学的巨大突破.肝癌肝移植术前肿瘤降期治疗可使不满足肝癌肝移植受者选择标准的患者能够被纳入移植标准,获得肝移植机会.对于乙型病毒性肝炎肝癌肝移植受者行抗病毒治疗,有助于降低移植术后乙型病毒性肝炎复发率,提高受者长期生存率.目前主张个体化的低剂量免疫抑制方案以达到最大限度保护移植肝脏功能,同时减轻其毒副作用,减少移植后肝癌复发.肝癌肝移植术后复发的防治可采用手术、TACE、局部消融以及放射免疫、靶向治疗、系统性化疗等手段,为受者制订个体化治疗方案.     

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??Neoadjuvant therapy of colorectal cancer GU Jin, DU Jing-zeng. Department of Colorectal Surgery, Beijing Cancer Hospital ,Beijing100142,China
Corresponding author:GU Jin, E-mail: zlguj@yahoo.com.cn
Abstract The principles of neoadjuvant therapy in colorectal cancer are as follows: 1. Rectal cancer patients of stage II and III should under neoadjuvant therapy. Specific strategies could be radiotherapy or with concurrent chemotherapy. Chemotherapy alone is not recommended. 2. Neoadjuvant chemotherapy is not recommended in colon cancer patients without metastasis. It is suggested only for patients with resectable liver metastasis to achieve the aim of tumor recession and diminishing micrometastasis.     

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??Convertible therapy for unresectable colorectal liver metastases ZHU De-xiang, REN Li, XU Jian-min. Department of General Surgery, Zhongshan Hospital, Fudan University; Institute of General Surgery, Fudan University; Colorectal Cancer Research Center, Fudan University, Shanghai 200032, China
Corresponding author??XU Jian-min, E-mail??xujmin@aliyun.com
Abstract Surgery is the most effective and the only potentially curative treatment for colorectal liver metastases (CRLM). However, most patients with CRLM are not suitable for liver resection. In recent years, a variety of cytotoxic drugs and/or targeted drugs were used to shrink unresectable liver metastases, and some patients were converted to resectable. Thereby they might be cured following surgical resection. Therefore the purpose of convertible chemothrapy is to get the best response rate, not the maximum response rate. It should choose efficient convertible chemotherapy with short courses for preoperative chemotherapy. For KRAS wild-type patients, cetuximab combined with FOLFOX/FOLFIRI, in which 5-fluorouracil is continuous infused, is recommended, and for KRAS-mutant patients, bevacizumab combined with two-drug chemotherapy regimen or three-drug chemotherapy regimen is considered. They should be operated as soon as the metastases become resectable.     

Distribution of retroperitoneal metastases after chemotherapy in patients with nonseminomatous germ cell tumors.

For patients with advanced nonseminomatous germ cell tumors a retroperitoneal lymph node dissection is routinely performed following chemotherapy if the serum tumor markers have returned to normal. Bilateral retroperitoneal lymph node dissection has been recommended because metastatic deposits may be widespread. The aim of this study was to describe the distribution of retroperitoneal metastases following chemotherapy in patients with nonseminomatous germ cell tumor and determine if the extent of the retroperitoneal lymph node dissection can be modified. We studied 113 patients who had initially bulky retroperitoneal disease and underwent retroperitoneal lymph node dissection following chemotherapy. For the purposes of this study teratoma and malignant germ cell tumor are referred to as tumor. The most common location of tumor was the para-aortic area (91%) in patients with a left primary tumor and the interaortocaval area (78%) in those with a right tumor. Tumor was located outside the boundaries of a modified retroperitoneal lymph node dissection in 14 of the 60 patients with residual disease but the tumor was present within a palpable mass in 6 of these 14 patients. If the residual mass was removed and a modified retroperitoneal lymph node dissection was performed only 9 of the 113 patients (8%) would have tumor left in the retroperitoneum. For a select group of patients with advanced nonseminomatous germ cell tumor treated with chemotherapy, resection of the residual mass combined with modified retroperitoneal lymph node dissection is appropriate.     

Fatal refractory hyperkalemia due to tumor lysis during primary resection for hepatoblastoma

Infants with large, rapidly growing tumors of the liver who exhibit preoperative signs of tumor necrosis (elevated uric acid or K+), having received no prior chemotherapy or radiation therapy, may be at risk for acute hyperkalemia during operative manipulation of the mass. In these patients, consideration should be given to careful monitoring of serum potassium throughout operative manipulation; cardiopulmonary bypass, to protect the heart from acute hyperkalemia; or to primary biopsy of the tumor with resection planned after chemotherapy. A case of fatal refractory hyperkalemia due to tumor lysis during a trisegmentectomy for hepatoblastoma in a 7-month-old girl who presented with a large, rapidly growing tumor and hyperuricemia is described.     

VAB-6 chemotherapy causes spurious elevation of alpha-fetoprotein associated with liver dysfunctions.

In order to elucidate the mechanism of elevation of alpha-fetoprotein (AFP) which we often observed during VAB-6 chemotherapy, we analyzed sequential changes of AFP, liver enzymes and bilirubin in 10 patients with evaluable disseminated testicular cancer who were treated with VAB-6 chemotherapy. None of the patients had previous liver disease or hepatic involvement. During the early phase of each course of chemotherapy, AFP showed a temporary elevation associated with reversible increase in liver enzymes and bilirubin. These changes returned to normal before the next course of chemotherapy. In each patient, marked tumor regression occurred as a result of VAB-6 chemotherapy. Nine of the 10 patients remain free of disease after treatment. We conclude that during VAB-6 chemotherapy, a temporary elevation of AFP is common, associated with reversible liver dysfunctions, and that this spurious elevation of the tumor marker, most likely caused by a heavy dose of cisplatin, should not be interpreted as related treatment failure.     

Low-grade gliomas in adults

Opinion statement Adult patients with a magnetic resonance scan suggestive of a supratentorial low-grade glioma should generally undergo at least a stereotactic biopsy to confirm the diagnosis and rule out an anaplastic glioma or a non-neoplastic lesion. Early tumor treatment should be given to patients with newly diagnosed low-grade gliomas who are over age 50 years, those who have headaches or neurologic deficits other than seizures, or those whose neuroimaging studies show tumor growth or mass effect. For younger patients presenting with seizures and no other neurologic symptoms, it is reasonable to defer therapy until there is clinical or radiographic tumor progression. When it is judged that intervention is necessary, patients should undergo the maximal surgical tumor resection, which preserves or improves neurologic function. For younger (>50 years) astrocytoma patients with a good tumor resection, radiation may be deferred until tumor progression. Early radiation should be given to astrocytoma patients who are older than 50 years of age at diagnosis (regardless of the type of surgery) or to younger patients who are judged to require early intervention but who are not candidates for aggressive surgical resection. The radiation dose for low-grade glioma should be 4500 to 5000 cGy, preferably with three-dimensional conformal ports. The same guidelines for management apply to patients with low-grade oligodendroglioma or oligoastrocytoma, except that chemotherapy is a reasonable alternative to radiation when it is judged that treatment other than surgical resection is required.     

Liver metastases of colorectal carcinoma--may the DRG-system influence the operative procedure?

The economic analysis of surgery in colorectal liver metastases reveals the different effectiveness of various follow-up programmes after curative surgery for colorectal cancer. Interval hepatic resection for synchronous liver metastases is recommended in the majority of cases with rectal cancer. This procedure provides benefits for the patient and the hospital under the economic point of view. The interval between primary tumor resection and surgery of liver metastases does not deteriorate the prognosis, on the contrary, unnecessary resections will be avoided if additional metastases will grow in the time between, excluding curative treatment (selection mechanism). The identical statement cannot be applied to patients with colon cancer, since the operative risk is only slightly increased in case of easily accessible liver metastases which may be removed simultaneously. However, also in these patients interval hepatic resection after neoadjuvant chemotherapy should be considered as a therapeutic option! In patients with multiple liver metastases liver surgery as well as radiofrequency ablation or a combination of both may be economically justified. Radiofrequency ablation is the preferred palliative procedure under aspects of cost-effectiveness, however, wether this procedure is superior to chemotherapy alone has not be evaluated so far in prospectively randomized trials.