不同部位胆管癌患者术后生存的影响因素分析

背景与目的 目前,胆管癌（CCA）的首选治疗仍为外科手术,但术后复发率较高,患者生存率低。对CCA患者术后生存影响因素的分析将有助于优化手术策略,从而一定程度上改善患者预后。因此,本研究探讨不同部位CCA患者术后生存的影响因素,为临床提供参考。方法 回顾性分析2011年1月—2020年3月133例行手术治疗的CCA患者临床病理资料,其中,肝内胆管癌（iCCA）58例,肝门胆管癌（hCCA）30例,远端胆管癌（dCCA）45例,分析临床病理特征与患者生存的关系与预后影响因素。结果 iCCA患者术后1、2、3、5年的生存率分别为41.38%、22.41%、8.62%、3.45%,单因素分析显示,iCCA患者的术后生存与合并胆道结石、术前血清白蛋白（ALB）水平、凝血酶时间、CEA、CA125、CA19-9、Child-Pugh分级、肿块最大直径、是否R₀切除、淋巴结转移情况、肿瘤分化程度有关（均P<0.05）;多因素分析显示,术前ALB水平、凝血酶时间、CA19-9、Child-Pugh分级、肿块最大直径及是否R₀切除是iCCA患者术后生存的独立影响因素（均P<0.05）。hCCA患者术后1、2、3、5年的生存率分别为43.33%、20.0%、6.67%、3.33%,单因素分析显示,hCCA患者的术后生存与术前CEA水平、是否R₀切除、淋巴结转移情况、肿瘤分化程度、肿块最大直径、是否侵犯门静脉有关（均P<0.05）;多因素分析显示,是否行R₀切除、淋巴结转移情况、肿瘤分化程度、是否侵犯门静脉及肿块最大直径是hCCA患者术后生存的独立影响因素（均P<0.05）。dCCA患者术后1、2、3、5年的生存率分别为62.22%、31.11%、17.78%、14.29%,单因素分析显示,dCCA患者的术后生存与淋巴结转移情况、肿瘤分化程度有关（均P<0.05）。多因素分析显示,淋巴结转移情况、肿瘤分化程度及是否R₀切除是dCCA患者术后生存的独立影响因素（均P<0.05）。dCCA患者术后生存时间优于iCCA和hCCA患者,但差异无统计学意义（均P>0.05）。结论 不同部位CCA有大致共同的预后影响因素,通过评估这些因素有助于预测CCA预后,完善对CCA患者的分层标准,优化术前和术后治疗方案,延长患者生存时间。     

肝门部胆管癌非手术治疗的研究进展及现状

肝门部胆管癌虽然发生率低,但预后较差,易复发,外科手术是目前唯一的治愈手段。虽然部分患者可以早期发现,手术根治,但多数患者被确诊时已属晚期,失去根治性手术治疗机会,非手术治疗可以缓解患者临床症状,降低并发症,甚至可以为手术治疗进行前期准备。非手术治疗包括非手术胆汁引流、放疗、化疗、新辅助放化疗、光动力学治疗等。本文就肝门部胆管癌非手术治疗的研究进展及现状进行综述。     

晚期结直肠癌的外科治疗进展

尽管结直肠癌的综合治疗有了很大的进展,但局部晚期(T3期和T4期)以及转移性结直肠癌的治疗仍然是具有挑战性的课题.新辅助放化疗、靶向治疗等研究取得了许多令人鼓舞的结果,但从外科处理的角度,仍然有诸多争议存在.包括对局部晚期结直肠癌多脏器切除的扩大根治指征、对结直肠癌肝转移和肺转移的最优化处理策略等.R0切除是转移病灶的首选处理策略,但仅适用于部分患者.利用化疗联合靶向药物的转化治疗策略将部分不可切除的转移肿瘤转化为可切除,也为进一步的外科治疗创造了机会.本文从局部晚期结直肠癌、结直肠癌肝和肺转移的外科治疗为切入点,简要阐述晚期结直肠癌的治疗进展.     

肝门胆管癌的肝移植治疗：附6例报告

背景与目的 不可切除的肝内胆管癌（hCCA）患者可考虑行肝移植治疗,但在某些方面仍存在争议。因此,本研究总结6例肝移植治疗不可切除hCCA临床疗效,以期为临床诊治提供参考。方法 回顾性分析2015年1月—2021年3月6例在上海交通大学医学院附属瑞金医院行肝移植治疗并规律随访的hCCA患者临床病理资料与生存情况。结果 6例肝移植术式均为原位经典全肝移植,术后病理：肿块型2例,管壁浸润型2例,内生型2例;肿瘤直径>3 cm者4例;周围神经浸润2例;门静脉侵犯3例;肝内转移2例;腺鳞癌1例,腺癌5例。组织学分级3例中分化G2,3例低分化G3;pTMN分期分别为II期1例,IIIa期1例,IIIb期1例,IIIc期2例,IV期1例。随访期间,3例存活,其中2例合并肝硬化失代偿内生息肉型腺癌患者获得长期无瘤生存,1例肿块型腺癌患者术前经新辅助放化疗后目前无瘤存活20个月;死亡3例,其中1例肿块型腺鳞癌患者术后存活18个月,2例管壁浸润型腺癌患者分别存活2个月与24个月。术前减黄操作,术后联用免疫抑制剂和化疗药物对于患者生存期无明显影响。结论 hCCA患者中,对于合并肝硬化的内生息肉型腺癌,且术前排除淋巴结转移者,即使术前不行新辅助放化疗直接行肝移植也可取得较好的疗效,但对有淋巴结转移与神经周围浸润者疗效差。     

肝门部胆管癌的治疗进展

目的 介绍肝门部胆管癌的治疗进展动态。方法 复习相关文献并作综述性报道。结果 扩大根治切除、新辅助放疗化疗、原位肝移植、光动力学治疗和分子放化疗均能有效地提高患者的生存率。结论 肝门部胆管癌的治疗仍是以手术切除为主的综合治疗。     

光动力疗法在肝外胆管癌的临床应用和研究进展

肝外胆管癌（eCCA）是一种起源于肝外胆管上皮细胞的高度侵袭性的恶性肿瘤,通过手术获得边缘阴性（R₀）切除是eCCA患者最佳治疗选择,然而大多数患者在初诊时已丧失了根治性手术治疗的机会,目前姑息性治疗中放、化疗效果不佳且存在较多不良反应,而胆道支架引流、免疫及靶向治疗虽有一定的疗效但也具有自身的局限性,光动力疗法（PDT）作为一种新兴的微创、具有良好耐受性和较小副作用的多学科交叉技术手段,不但可抑制肿瘤生长,还可联合多种治疗方式提高不可切除eCCA患者的生存期和生活质量,因而具有广阔的临床运用前景。本文主要从PDT的机制、光源路径和光敏剂的运用现状及其联合治疗在临床中的应用进行归纳和总结,并且针对目前PDT在治疗eCCA中的临床困境提出了潜在的应对策略,旨在为eCCA患者的临床治疗方案和科研方向提供依据和参考。     

肝门部胆管癌外科治疗进展

肝门部胆管癌（HCCA）是指发生在左右肝管、汇合部以及肝总管上段,起源于胆管上皮细胞的一种恶性肿瘤。其发病机制的复杂性、起病症状的隐匿性、解剖结构的特殊性,使得多数患者确诊时已经处于中晚期,是当前临床诊治的难点。仅约20%的患者能得到根治性切除,R₀切除率为50%~92%。术后复发率高,预后差,5年生存率仅10%~42%。目前手术切除仍是改善预后的主要有效治疗方式。随着外科各项技术进步,HCCA的外科治疗取得一定进展,但仍面临诸多挑战。笔者就HCCA的外科治疗最新的研究进展及相关争议进行以下综述。     

临界可切除肝癌行肝动脉灌注化疗联合肝动脉栓塞术转化治疗的疗效

背景与目的 对于临界可切除的原发性肝癌,目前我国原发性肝癌诊疗指南（2022年版）推荐仍是肝动脉插管化疗栓塞术（TACE）、外科手术切除或系统抗肿瘤治疗。当前原发性肝癌的术前转化治疗已经取得了很大的进展,但对于具体转化治疗方案尚在探索中。本研究探讨临界可切除肝癌行FOLFOX方案的肝动脉灌注化疗（HAIC）联合肝动脉栓塞术（TAE）局部转化治疗的真实世界疗效。方法 收集2019年4月—2022年2月采用FOLFOX方案的HAIC联合TAE转化治疗的22例临界可切除（CNLC分期Ⅱb期）原发性肝癌患者的临床资料,根据改良实体瘤疗效评价（mRECIST）标准评估肿瘤客观缓解率（ORR）、疾病控制率（DCR）,分析转化手术切除率和术后标本的病理缓解率以及转化治疗后手术与未手术患者的预后情况。结果 22例患者均完成HAIC联合TAE治疗,主要不良反应包括上腹痛、低热、短期的肝功能损害等,但没有发生不可逆的严重并发症。转化治疗后,肿瘤ORR、DCR分别为63.6%、86.3%,但有3例（13.6%）患者出现肿瘤进展。转化治疗结束后14例患者行肝癌手术切除,转化手术切除率为63.6%,手术顺利,均能达到R₀切除,无术后死亡病例。术后病理检查有10例（71.4%）为主要病理缓解（MPR）,但无1例能达到完全病理缓解（CPR）。14例手术患者的无复发生存期平均为14.7个月;手术患者的总生存期明显优于未手术患者（22.7个月vs. 13.2个月,P=0.018）。结论 HAIC联合TAE转化治疗对于临界可切除肝癌具有良好的耐受性,是安全可行的,能取得较高ORR、DCR和转化手术切除率。虽然大多数术前转化治疗后能达到MPR,但CPR较低,手术切除仍是肝癌转化治疗后患者获得长期生存的关键。     

侵犯第一肝门肝内胆管癌手术的临床价值

背景与目的 侵犯第一肝门肝内胆管癌（HICC）侵袭性强,病理生理复杂。外科手术是首选的治疗方法,但R₀切除率低,预后差。本文通过分析接受手术治疗的HICC患者预后情况,探讨其手术治疗的临床价值。方法 回顾性分析2010年11月—2016年6月在东方肝胆外科医院手术治疗98例HICC患者的临床及病理资料。根治手术67例,姑息手术31例,其中R₁切除3例,R₂切除28例。行根治手术患者中,32例合并肝门血管侵犯（HVI）,35例无HVI。结果 全组患者1、3、5年总生存率为46.5%、11.7%、5.8%,中位生存期（mOS）12.0个月。根治手术患者预后优于姑息手术组（mOS：14.0个月vs. 7.0个月,P=0.004）。无HVI患者预后优于有HVI患者（mOS：21.0个月vs. 9.0个月,P=0.002）及行姑息手术患者（mOS：21.0个月vs. 7.0个月,P<0.001）。有HVI的根治手术患者与行姑息手术患者的预后差异无统计学意义（mOS：9.0个月vs. 7.0个月,P=0.192）。Cox多因素分析显示,肝门血管受侵（HR=2.02,95% CI=1.19~3.44,P=0.009）及CA19-9高水平（HR=1.89,95% CI=1.05~3.43,P=0.035）是HICC患者根治手术预后的独立危险因素。有HVI与无HVI的患者间比较发现,年龄>60岁及肿瘤直径≥5 cm的患者HVI率更高（均P<0.05）。结论 HICC切除率低,预后差。肝门血管受侵及CA19-9高水平是影响HICC根治术后预后的危险因素,合并HVI的HICC患者术后无生存获益。     

结直肠癌肝转移的微创治疗策略

结直肠癌是世界范围内常见的恶性肿瘤,也是肿瘤导致死亡的重要原因。肝脏是结直肠癌最常见的转移部位,约20%的患者伴有同时性肝转移,另20%患者在疾病的发展中也出现肝转移。结直肠癌肝转移（CRLM）是目前结直肠癌治疗的重点与难点,也是影响患者预后的重要因素。手术切除仍然是患者长期生存甚至治愈的最佳治疗选择,其中微创切除更是兼具微创的优势与根治的效果,长期的肿瘤学疗效也与开放手术相当。但受限于肿瘤大小、位置分布等解剖因素、患者的肝脏功能以及一般状态等因素,只有少数患者在初诊时适合手术切除。其他微创治疗策略包括消融治疗、立体定向放射治疗、介入治疗等,这些技术的发展为不可手术切除的患者提供了新的治疗机会,同时也提高了单纯系统治疗的生存率。消融治疗对于选择性的患者兼具有微创与类似手术的根治性效果,对于深部肿瘤也更具优势。立体定向放射治疗是不适合手术切除或消融困难或复发病灶的重要替代选择。Y⁹⁰选择性体内放射治疗更是兼具肿瘤控制与增大余肝的双重作用,在转化治疗时代其地位也不断上升。随着微创理念的深化与技术的进步,CRLM的微创治疗取得一定进展,但仍面临诸多挑战,如在精准、个体化与转化治疗时代微创治疗策略如何合理地联合或序贯使用等。在选择微创治疗策略时,应该根据多学科团队的指导进行个体化评估和综合治疗,尽可能实现R₀切除或无疾病证据状态,从而最大程度地提高患者的长期生存率。本文就近年来CRLM的微创治疗策略进行综述,以期为临床治疗的选择提供参考。     

Aplicabilidad y resultados del trasplante hepático combinado con quimiorradioterapia neoadyuvante en el tratamiento del colangiocarcinoma perihiliar irresecable

BackgroundIn 2007, a multicenter protocol was developed in Catalonia, Spain, combining neoadjuvant chemoradiotherapy and liver transplantation (LT) for those patients with unresectable hilar cholangiocarcinoma (hCCA).AimTo analyse the effectiveness of the neoadjuvant chemoradiotherapy and LT for those patients enrolled in the protocol based on intention-to-treat.MethodsObservational multicenter study which includes patients ≤ 68 years-old diagnosed with unresectable, solitary tumors ≤ 3 cm in radial diameter, without evidence of lymph node metastases. The protocol was based on a strategy of neoadjuvant therapy with high-dose radiation (45 Gy in total) plus intravenous fluorouracil (5-FU) given as a daily bolus for the first 3 days of radiation follow by oral capecitabine until transplantation. The patient was included in waiting list for LT if no evidence of disseminated disease was found.ResultsBetween 2007 and 2018, 13 patients were enrolled in the transplant protocol. Of those, 61% (8/13) of the patients were transplanted. The average time spent on the waiting list was 122 days (range 5-192). Intent-to-treat survival was 69% and 39% at one and 5 years. Post-transplantation overall survival was 87% and 62% and 29% recurrence rate at 5 years.ConclusionThe suitability of the neoadjuvant chemoradiotherapy and LT protocol was 61% in our series with long-term overall survival and should be considered as an alternative to resection for patients with localized node-negative hCCA.     

Neoadjuvant therapy in the treatment of hilar cholangiocarcinoma:Review of the literature

Cholangiocarcinoma(CCA) is a malignant tumor of the biliary system and includes, according to the anatomical classification, intra hepatic CCA(iCCA),hilar CCA(hCCA) and distal CCA(dCCA). Hilar CCA is the most challenging type in terms of diagnosis, treatment and prognosis. Surgery is the only treatment possibly providing long-term survival, but only few patients are considered resectable at the time of diagnosis. In fact, tumor's extension to segmentary or subsegmentary biliary ducts, along with large lymph node involvement or intrahepatic metastases, precludes the surgical approach. To achieve R0 margins is mandatory for the disease-free survival and overall survival. In case of unresectable locally advanced hCCA, radiochemotherapy(RCT) as neoadjuvant treatment demonstrated to be a therapeutic option before either hepatic resection or liver transplantation. Before liver surgery, RCT is believed to enhance the R0 margins rate. For patients meeting the Mayo Clinic criteria, RCT prior to orthotopic liver transplant(OLT) has proved to produce acceptable 5-years survivals. In this review, we analyze the current role of neoadjuvant RCT before resection as well as before OLT.     

Liver transplantation for hilar cholangiocarcinoma: A systematic review

Patients with hilar cholangiocarcinoma (hCCA) have advanced disease at presentation and therefore curative treatment options are limited. Liver transplantation (LT), in the case of unresectable disease, is theoretically an attractive option, as it offers the maximum resection margin and at the same time removes the underlying parenchymal liver disease. In the past years a number of studies have aimed to evaluate to potential beneficial role of neo adjuvant therapy followed by LT for treating patients with unresectable hCCA. The objective of our systematic review was to collect and evaluate long-term outcomes of patients with hCCA undergoing LT. A systematic search of 4 electronic databases (Medline, Scopus, Google Scholar and ClinicalTrails.gov databases) was performed for articles published between January 2000 and May 2019. A total of 13 studies with 698 patients were finally included in the present systematic review. A proportion of 74.4% of patients received combination of chemotherapy and radiation as a part of neoadjuvant therapy. One-, 3- and 5-year overall survival rates ranged greatly among the included studies from 58% to 92%, 31% to 80% and 20% to 74%, respectively. Recurrence rates ranged from 16% to 61%, whilst perioperative mortality ranged from 0% to 25.5%. LT could provide acceptable long-term outcomes in the setting of neoadjuvant chemoradiation and strict patient selection criteria. Taking into account organ shortage, combined with the lack of level I evidence, more prospective randomized trials are needed in order to establish certain indications, rigorous criteria and standardized protocols for LT in hCCA and provide the maximal potential benefits for these patients.     

肝移植能否用于治疗胆管癌

胆管癌包括肝内和肝外胆管癌，传统的治疗方法首选根治性手术切除，胆管癌恶性程度高，手术切除率低，病死率高，早期肝移植治疗胆管癌的效果差，多数患者术后早期复发，长期生存率较低，近年随着供体短缺问题越来越严重，一些移植中心已将胆管癌作为肝移植的禁忌证，但也有报道反对这一观点，认为结合放化疗等辅助治疗的肝移植要优于手术切除，能明显提高患者生存率。本文结合文献和我院经验，对肝移植能否用于治疗胆管癌这一有争论的问题进行简单讨论。     

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.     

Cholangiocarcinoma

The diagnosis of cholangiocarcinoma can now be made with greater rapidity and accuracy. In the clinical setting of obstructive jaundice, a CT scan or sonogram may suggest cholangiocarcinoma if dilated intrahepatic ducts are seen with a nondilated extrahepatic biliary tree. The diagnosis is confirmed by cholangiography, and the tumor is staged by the combination of cholangiography and angiography. If the tumor extensively involves both lobes of the liver or involves the main portal vein or hepatic artery, the lesion is considered unresectable. These patients are best palliated nonoperatively, but they should still have an attempt at a tissue diagnosis, as various other lesions can masquerade as cholangiocarcinoma. In comparison, if the tumor is confined to or is distal to the hepatic duct bifurcation, extends into only one lobe of the liver, or involves only the right or the left portal vein or hepatic artery, the lesion may be resectable, and exploration is indicated. As many as half of all patients explored with curative intent will have a successful resection. Various surgical options are appropriate for patients undergoing tumor resection, depending on the site and extent of the lesion. Similarly, several surgical options are possible for palliation in patients with unresectable cholangiocarcinoma. The role of radiotherapy in the management of cholangiocarcinoma is uncertain. Our results, like those of many other retrospective analyses, suggest that radiotherapy prolongs survival after curative resection as well as after palliative stenting. However, further data from randomized studies are necessary to support or refute this impression. Further studies of adjuvant chemotherapy or hormonal therapy will also be necessary to improve patient survival.     

Effect of neoadjuvant therapy on local recurrence after resection of pancreatic adenocarcinoma

BACKGROUND: It is unknown whether neoadjuvant chemoradiotherapy, compared with adjuvant chemoradiotherapy, decreases the rate of local recurrence after resection of pancreatic adenocarcinoma. STUDY DESIGN: This is a retrospective case review of 102 patients with pancreatic adenocarcinoma who underwent pancreatic resection between 1993 and 2005. RESULTS: Of 102 patients with pancreatic adenocarcinoma who underwent surgical resection, 19 (19%) had no additional treatment, 41 (40%) underwent adjuvant chemoradiotherapy, and 42 (41%) were treated preoperatively with neoadjuvant chemoradiotherapy. Patients selected to receive neoadjuvant therapy were more likely to have locally advanced tumors. Based on initial CT scan, the percentage of patients with unresectable or borderline resectable tumors in the neoadjuvant group was 67%, compared with 22% in the adjuvant group. Nevertheless, patients receiving neoadjuvant chemoradiotherapy were less likely to have a local recurrence develop than patients receiving adjuvant chemoradiotherapy (5% versus 34%, p = 0.02). For those patients with tumors determined to be resectable on initial CT scan, local recurrences were observed in 31% (10 of 32) of patients in the adjuvant therapy group, compared with only 7% (1 of 14) of the neoadjuvant group. Intraoperative radiation therapy, administered to 51% of patients, was not associated with a lower rate of local recurrence. CONCLUSIONS: Neoadjuvant chemoradiotherapy is associated with improved local tumor control in patients undergoing resection for pancreatic carcinoma.     

Novel Multimodality Treatment Sequencing for Extrahepatic (Mid and Distal) Cholangiocarcinoma

Neoadjuvant chemoradiation has demonstrated significant advantages in the management of pancreatic adenocarcinoma. A similar tumor in a nearby anatomical location is extrahepatic cholangiocarcinoma, which has proven to be largely unresponsive to current forms of therapy. Neoadjuvant therapy for hilar cholangiocarcinoma has been combined with surgical resection and/or liver transplantation with a 25–33 % complete pathological response rate. We propose a wider application of neoadjuvant chemoradiation for patients with distal cholangiocarcinoma and present our rationale for this form of treatment sequencing.