原发性肝癌肝移植相关热点研究进展

原发性肝癌是我国最常见的恶性肿瘤之一,其预后较差。随着肝移植技术和围手术期管理水平的提高,以及肝移植基础研究的不断深入,肝移植现已成为治疗肝癌的常规方法,肝癌患者的预后也因此得到很大改观。但目前学界尚未就肝癌患者的手术方式选择、肝移植适应证、围手术期辅助治疗和移植免疫等问题达成共识。本文就上述问题结合最新文献进行阐述。     

经肝动脉灌注化疗在肝癌围术期的作用

原发性肝癌（以下简称“肝癌”）是最常见的消化道恶性肿瘤之一。超过60%的肝癌患者初次确诊时已处于中晚期,失去了接受根治性手术的机会;即使接受根治性切除术的患者,其术后的5年复发率也高达80%。以奥沙利铂/5-FU方案为主的肝动脉灌注化疗作为我国中晚期肝癌患者的重要治疗手段之一,展现出较好的肿瘤反应率和手术转化率,对于其在肝癌患者围手术期的应用方兴未艾。现总结分析国内外肝动脉灌注化疗在肝癌患者围手术期的研究进展,系统阐述其发展衍变过程及其在肝癌治疗中的新作用。     

肝癌患者肝动脉化疗栓塞术后的护理体会

原发性肝癌由于起病隐匿,患者就诊时大多已属中晚期,极大限制了手术切除治疗方法受到限制。肝动脉插管化疗栓塞（TACE）是目前非手术治疗原发性肝癌的首选方法,它既能延长不能手术切除肝癌患者的生存期,又可使部分患者获得2期手术切除的机会。我科2007年5月-2008年5月对所收治的38例中晚期原发性肝癌患者进行了TACE治疗,效果满意。现将TACE围手术期的临床观察和护理体会报告如下。     

原发性肝癌肝移植术后化疗效果的初步观察

目的：探讨原发性肝癌肝移植后化疗的安全性和疗效。方法：回顾性分析22例因原发性肝癌而行肝移植病人的临床资料，以求进一步探明肝癌的肝移植指征，术后化疗时机、化疗方案、化疗的副作用及化疗对近、远期生存率的影响。结果：2002年6月至2003年7月，共有22例原发性肝癌进行肝移植；18例最迟于术后5周内进行第1次全身化疗，累计完成化疗41次；其余4例因各种原因未行化疗，包括1例意外发现的癌和1例小肝癌。8例出现肝功能损害，6例发生白细胞减少，仅2例需重组人集落刺激生长因子治疗。结论：原发性肝癌是肝移植的一个主要适应证；结合术后化疗可延长复发时间，提高生存率；且病人可以安全耐受。     

原发性肝癌合并严重肝硬化门静脉高压症的外科治疗选择

目的探讨原发性肝癌合并严重肝硬化门静脉高压症的外科治疗方法及疗效。方法回顾性分析我院1998年1月至2006年8月手术治疗的肝癌合并严重肝硬化门静脉高压症161例，其中行脾切除＋贲门周围血管离断术联合肝癌局部根治性切除70例，脾切除＋贲门周围血管离断术联合术中射频消融治疗68例，肝移植23例。结果肝癌切除组、术中射频治疗组和肝移植组术后5年生存率分别为34．3％、39．7％和82．6％，并发症发生率分别为20．0％、4，4％和8．7％，无围手术期死亡。结论对于可切除的原发性肝癌合并严重肝硬化门静脉高压症的患者，在加强围手术期处理的同时根据病情合理选择外科治疗方法，可以有效地治疗肝癌和门静脉高压症，提高患者的生存质量及延长生存期。     

难治性复发肝肿瘤的肝移植

目的探讨难治性复发肝肿瘤行肝移植的难点及围手术期处理注意事项。方法总结2003年9月至2004年9月我科施行的14例肝移植，其中难治性复发肝肿瘤9例（A组），其余5例术前未接受任何有创治疗（B组），分析两组术前治疗情况、术中探查情况、病肝游离时间、无肝期时间、术中出血、输血及止血药物使用情况、手术死亡率、术后肾上腺糖皮质激素的减撤及化疗等情况。结果A组术中病肝游离时间、无肝期时间明显较B组长，出血、输血量及止血药物的用量均明显大于B组，手术死亡2例均为A组病例。术后存活的肝癌病例均行全身化疗，肾上腺糖皮质激素于3个月内停药，至今均无瘤生存。结论难治性复发肝肿瘤的肝移植较一般肝移植手术难度大，对术者要求更高，术中监护和补充凝血因子极为重要。围手术期抗肿瘤治疗、术后尽早减撤肾上腺糖皮质激素对术后无瘤生存有积极意义。     

肝移植治疗原发性肝癌切除术后肝内复发七例

目的 探讨对原发性肝癌切除术后肝内复发患者进行肝移植手术的适应证和围手术期的治疗经验.方法 回顾性分析2000年9月至2005年9月间7例原发性肝癌切除术后肝内复发的患者接受原位肝移植治疗的临床资料,其中男性6例,女性1例,平均年龄43.7岁,肝移植术前均经病理学检查确诊为原发性肝癌,肿瘤组织学分级为高、中分化,肝癌切除术后无瘤期为6～31个月,均未发生肿瘤细胞侵犯大血管和肝外转移.所有患者均采用改良背驮式肝移植术.术后采用他克莫司(或西罗莫司)+霉酚酸酯+激素的三联免疫抑制方案.观察肝移植术后受者并发症及存活率情况.总结肝移植治疗原发性肝癌切除术后肝内复发的经验.结果 所有受者肝移植手术过程顺利,围手术期无死亡.1例术后22 h发生腹腔出血,1例术后13 d发生腹腔感染,1例术后4个月发生门静脉血栓,其余未发生严重并发症,7例受者均顺利出院.有3例受者分别于移植术后9、13及19个月时,因肿瘤复发而死亡,其余4例均长期无瘤存活,最长已达52个月.受者的1、2年存活率分别为85.7%和57.1%.结论 肝移植能有效治疗原发性肝癌切除术后肝内复发,受者适应证的选择和围手术期的辅助治疗非常关键.     

肝癌患者在肝移植围手术期施行化疗的临床意义

肝癌患者在肝移植围手术期术前施行经肝动脉栓塞化疗（HACE）可以防治肝移植期间的肿瘤进展，提高肝移植手术成功率；且对较大的肿瘤可起到延缓生长，增加肝移植或肝切除手术机会，提高肝癌患者生存质量，同时延长无病生存期。肝移植术后辅助化疗作为消灭微小转移灶的一种手段已被应用于临床治疗观察，对改善肝癌患者肝移植后的生存率可能有效，亦有可能推迟肿瘤复发。因此，认为辅助化疗是一种安全、可行的治疗方法，但就其治疗效果还有待于大规模、多中心、前瞻性的随机对照研究验证。     

肝脏移植治疗原发性肝癌20例报告

目的　探讨原位肝移植技术在治疗原发性肝癌中的地位和疗效。　方法　对1993年4月至2000年6月中山医科大学器官移植中心进行的20例原位肝移植术治疗原发性肝癌临床资料进行回顾性研究。其中大肝癌14例（直径＞5cm）,小肝癌6例（直径≤5cm）。　结果　大肝癌组肝移植术后平均存活6.5个月,肝癌复发率为71%(10/14);小肝癌组移植术后1、2年存活率分别为83％(5/6)和67%（4/6）,肝癌复发率为17%(1/6),两组肝癌复发率的差异有显著意义(P＜0.05)。　结论肝移植对肝癌单发,直径小于或等于5cm,无血管侵犯的小肝癌有良好的疗效;对部分病例选择适当的大肝癌患者可获得较好的姑息疗效;肝移植围手术期辅助化学药物治疗可能会减少肝癌复发。     

不能切除肝癌的外科治疗

近年来随着外科技术的进步和治疗药物的发展,对不能切除的原发性肝癌的外科治疗手段越来越多,使原发性肝癌的疗效有了明显提高。综合起来,目前对不能切除肝癌的外科治疗手段主要有肝移植、二期切除、肝动脉结扎插管化疗、微波治疗、冷冻治疗、瘤内射频热分离治疗、超声热疗等。一、肝移植肝移植作为不能切除肝癌的治疗手段目前尚存在争议。在开展肝移植的早期,不能手术切除的中晚期肝癌是肝移植的主要适应证。世界上最初的10例临床肝移植,其中8例是各种肝癌。但是,随着肝移植技术的发展,对不能切除肝癌施行肝移植却存在很大争议。反对者认为…     

Surgical treatment for recurrent hepatocellular carcinoma: Current status and challenges

Primary liver cancer is the sixth most commonly diagnosed cancer and was the third leading cause of cancer deaths worldwide in 2020. It includes hepatocellular carcinoma (HCC) (representing 75%-85% of cases), intrahepatic cholangiocarcinoma (representing 10%-15% of cases), and other rare types. The survival rate of patients with HCC has risen with improved surgical technology and perioperative management in recent years; however, high tumor recurrence rates continue to limit long-term survival, even after radical surgical resection (exceeding 50% recurrence). For resectable recurrent liver cancer, surgical removal [either salvage liver transplantation (SLT) or repeat hepatic resection] remains the most effective therapy that is potentially curative for recurrent HCC. Thus, here, we introduce surgical treatment for recurrent HCC. Areas Covered: A literature search was performed for recurrent HCC using Medline and PubMed up to August 2022. Expert commentary: In general, long-term survival after the re-resection of recurrent liver cancer is usually beneficial. SLT has equivalent outcomes to primary liver transplantation for unresectable recurrent illness in a selected group of patients; however, SLT is constrained by the supply of liver grafts. SLT seems to be inferior to repeat liver resection when considering operative and postoperative results but has the major advantage of disease-free survival. When considering the similar overall survival rate and the current situation of donor shortages, repeat liver resection remains an important option for recurrent HCC.     

DC-CIK过继细胞免疫治疗原发性肝癌的研究进展

【摘要】〓原发性肝癌(以下简称肝癌)临床往往较难早期发现,确诊时往往病情已进入中、晚期,病死率高。目前肝癌的治疗主要是以手术切除、肝移植、局部消融、化学治疗栓塞及其他局部区域治疗、分子靶向治疗等,但这些方法的治疗效果并不理想,患者5年存活率仍然较低。目前细胞免疫治疗现在得到了越来越多的重视,采用树突状细胞(DC)联合细胞因子诱导的杀伤细胞(cytokine induced killer, CIK)的细胞免疫治疗是其中方法之一。DC和CIK细胞是恶性肿瘤免疫治疗的两个重要因素,两者之间的相互作用及所诱发的免疫应答是免疫治疗的重要部分。现就DC-CIK过继细胞治疗原发性肝癌的研究进展予以综述。     

Therapie des hepatozellulären Karzinoms vor Lebertransplantation

Liver transplantation is the optimal therapy for patients with non-resectable early stage hepatocellular carcinoma (HCC) which is limited to the liver. During the sometimes long waiting period patients usually receive neoadjuvant bridging therapy to avoid tumor progression. The armamentarium of bridging therapies includes local ablative and systemic therapies as well as liver resection. The oncological benefit of neoadjuvant therapy for patients who receive a liver transplantation is unclear; however, bridging therapy keeps patients eligible for transplantation in the formal framework of current allocation rules. Moreover, response to therapy may serve as a surrogate marker for favorable tumor biology and may therefore help to guide the selection process for patients undergoing liver transplantation for HCC.     

预防肝癌肝移植后肿瘤复发转移的研究进展

目前即使是全球最先进的移植中心也有约1/3的受者为肝癌患者,原发性肝癌特别是早期肝癌已被世界多数器官移植中心列为肝移植的手术适应证之一,然而,由于术后肿瘤的转移和复发,很多患者将于术后2年左右死亡,其5年生存率仅为良性终末期肝病患者的50%.目前对此现象的研究无论从机制上、治疗上都尚浅尚少,如何预防肿瘤复发已成为肝移植外科必须面对的严峻挑战.显然,发现肝癌肝移植术后复发的分子机制及易感因素、探索适宜的肝癌肝移植标准以及加强围手术期处理是提高疗效的必由之路.     

Transplantation After Successful Downstaging by Multimodal Treatments of American Joint Committee on Cancer Stage IIIB Hepatocellular Carcinoma With Portal Vein Thrombi: A Case Report

The effective treatment for hepatocellular carcinoma (HCC) with American Joint Committee on Cancer stage IIIB remains controversial and challenging because of the high recurrence rate after resection and low survival rate. The median survival of those with macroscopic portal vein tumor thrombus (PVTT) is short. We reported such a case which received liver transplantation (LT) after successful consecutive downstaging therapies. A 40-year-old man with alcohol related liver cirrhosis and repeated esophageal varices bleeding had HCC with tumor thrombi in right main portal vein and the second portal branch of segment VI (stage IIIB). The received percutaneous alcohol injection, radiofrequency ablation, 8 sessions of transcatheter hepatic arterial chemoembolization, radiotherapy, and target therapy with sorafenib. Computed tomography (CT) scan and magnetic resonance imaging after treatments showed no viable fragments in the tumor and revealed both the right main portal vein and V1 branch were patent. One month later, the patient received a deceased LT. The perioperative course was rather smooth. After discharge, the interval follow-up CT studies of the chest and liver and whole body bone scan showed no tumor recurrence or metastasis up to 20 months postoperation.     

局部进展期胃癌围手术期治疗的现状与展望

在我国,每年新增的胃癌患者中,局部进展期胃癌（LAGC）占大宗。D 2根治性手术及其术后辅助化疗已取得了普遍的共识,该治疗策略明显改善了LAGC患者的预后,但是术后复发率仍然较高（50%~80%）,致使远期疗效难以进一步提高。围手术期治疗,特别是术前新辅助治疗（NAT）能否提高LAGC疗效,已受到越来越多的关...     

Liver Transplantation After Downstagings of Ruptured Advanced Hepatocellular Carcinoma in Cirrhotic Liver: Is It Advisable? A Case Report

Spontaneous rupture of hepatocellular carcinoma (HCC), defined as T4 in TNM stage by the American Joint Committee on Cancer (eighth edition), is a serious life-threatening complication. Effective treatment remains challenging because of a high 1-month mortality, a short median survival, and the potential of peritoneal metastasis. We reported on a case that received a living related donor liver transplantation (LDLT) after successful consecutive downstaging therapies. A 63-year-old man with alcohol-related liver cirrhosis and multiple HCC developed spontaneous rupture and hemoperitoneum. He received 3 sessions of transcatheter hepatic arterial chemoembolization and target therapy with sorafenib. Computed tomography scans and magnetic resonance imaging after 11 months of treatment showed that the patient's HCCs fulfilled the Milan criteria and the University of California San Francisco criteria prior to LDLT. The perioperative course was rather smooth. After discharge, interval follow-up computed tomography studies of chest and liver and a whole-body bone scan showed no tumor recurrence or metastasis up to 20 months post-operation. Successful downstaging therapies of ruptured HCC to fulfill Milan criteria to receive liver transplantation is advisable in highly selected patients.     

Liver resection and transplantation in the management of hepatocellular carcinoma: a review

Hepatocellular carcinoma (HCC) accounts for more than 80% of all primary liver cancers and is one of the most common malignancies worldwide. Most patients with HCC also suffer from concomitant cirrhosis, which is the major clinical risk factor for hepatic cancer and results from alcoholism, infection with the hepatitis B or hepatitis C virus, and other causes. HCC is often diagnosed at an advanced stage, when established treatment options provide limited benefit. Effective treatment for HCC includes liver resection and liver transplantation. Under most clinical circumstances, those options provide a high rate of complete response and are thought to improve survival. Partial hepatectomy is the therapy of choice in patients with HCC and a noncirrhotic liver. Usually, liver transplantation is not indicated for such patients, although in individual cases, transplantation may be considered. For most cirrhotic patients who fulfill the Milan criteria, liver transplantation is the ultimate treatment option. Liver transplantation restores liver function and ensures the removal of all hepatic foci of tumor as well as tissue with a high oncogenic potential for early tumor recurrence. Because of the present lack of available organs, living-donor liver transplantation (LDLT) is an increasingly popular alternative. LDLT enables recipients to avoid a long pretransplantation waiting time and increases the number of livers available for transplantation. It is also the most effective approach to reducing the dropout rate. Strategies to reduce tumor growth in patients who are awaiting liver transplantation are important to ensure that those individuals continue to fulfill the Milan criteria for transplantation. For that purpose, using ablative techniques or chemoembolization to control local tumor growth is useful.     

Role of transarterial chemoembolization for hepatocellular carcinoma before liver transplantation with special consideration of tumor necrosis

Abstract:  Several authors suggest that local ablative therapies, specifically transarterial chemoembolization (TACE), may control tumor progression of hepatocellular carcinoma (HCC) in patients who are on the waiting list for liver transplantation (orthotopic liver transplantation, OLT). There is still no evidence if TACE followed by OLT is able to prevent recurrence of tumor, to prolong survival rate of the patients on the waiting list, or to improve the survival after OLT. We report 27 patients with HCC who underwent OLT. From these patients, 15 were pre-treated with TACE alone or in combination with percutaneous ethanol injection (PEI) or laser-induced thermo therapy (LITT). Mean time on the waiting list was 214 d for treated patients and 133 d for untreated patients. Comparing pre-operative imaging and histopathological staging post-transplant, we found 13 patients with tumor progression out of which five were treated with TACE. In two of the TACE patients a decrease of lesions could be achieved. In a single patient, there was no evidence of any residual tumor. Only one patient displayed tumor progression prior to OLT despite undergoing TACE. Comparison of outcome in patients undergoing TACE or having no TACE was not statisitically significant (p = 0.5). In addition, our analysis showed that progression either in the total study population or in the TACE group alone is associated with a significant poorer outcome concerning overall survival (p = 0.02 and p = 0.02).