肝癌肝移植后亚砷酸化疗的应用

背景：移植后肿瘤复发是影响肝癌肝移植疗效的主要因素,如何防止肝癌肝移植后肿瘤复发是目前肝移植研究的热点问题之一。亚砷酸全身化疗被认为对中晚期肝癌具有一定作用,但在肝移植后的应用还未见报道。目的：观察超出米兰标准的肝癌患者肝移植后应用亚砷酸全身化疗的对肿瘤复发的干预效果。方法：对23例超出米兰标准的肝癌患者肝移植后采用亚砷酸行预防性化疗：静脉滴注10mg/d,连续使用7d后间隔7d,重复4次为1个疗程,患者接受1~4个疗程。观察以上使用亚砷酸化疗患者的生存、肿瘤复发情况,以及化疗不良反应,并与同期16例未使用化疗的肝癌肝移植患者相比较。结果与结论：经过3~32个月随访,共30例患者出现肝癌复发,化疗组16例,非化疗组14例,复发部位最常见于肺部、移植肝及骨骼。化疗组与非化疗组肿瘤复发率差异无显著性意义,但化疗组复发时间明显延迟（P=0.026）;两组6个月、1年生存率差异无显著性意义,化疗组2年生存率显著高于非化疗组（P=0.037）;两组6个月无瘤生存率差异无显著性意义,1年、2年无瘤生存率化疗组显著高于明显非化疗组（P=0.030,0.023）。亚砷酸使用过程中未发现严重不良反应。提示肝癌肝移植患者静脉使用亚砷酸化疗可以延迟肿瘤复发,提高生存率。     

索拉非尼治疗肝细胞性肝癌肝移植后的复发

背景:肝细胞肝癌肝移植后肿瘤复发转移十分常见,肿瘤进展迅速,缺乏有效治疗方法。目的:观察索拉非尼联合介入治疗肝细胞性肝癌肝脏移植后复发的疗效。方法:选择24例肝细胞性肝癌肝移植后肿瘤复发患者,其中单纯接受介入治疗者16例,接受索拉非尼联合介入治疗者8例,通过Log-rank检验比较两组患者移植后6个月生存率、1年生存率、移植后无瘤生存时间。结果与结论:介入治疗组移植后平均无瘤生存时间为95d,联合治疗组为100d,两组间差异无显著性意义(P=0.2805)。移植后终生随访,介入化疗组16例全部死亡,中位生存时间为211d,6个月生存率为69%,1年生存率为25%。联合治疗组死亡2例,6个月生存率为100%,1年生存率为100%,两组间差异有显著性意义(P<0.0001)。说明对于肝细胞性肝癌肝移植后肿瘤复发患者,采用索拉非尼+介入治疗联合治疗方案可显著提高患者生存期及生存率。     

原位肝移植治疗原发性肝癌

背景:肝移植可完整切除病肝,远期疗效优于肝切除,其5年存活率可达70%H1.此外,肝移植还可避免在肝功能不良的情况下肝切除带来的术后肝功能不全的严重风险.目的:回顾性分析原发性肝癌原位肝移植治疗效果及意义.方法:对解放军南京军区福州总医院肝胆外科1980-03/2008-12因原发性肝癌行原位肝移植术患者75例术后生存及肿瘤复发情况进行总结分析.结果与结论:75例患者术后1,2,3年的总体生存率及无瘤生存率分别为:86.6%,66.70%.53.3%及65.2%,53.9%,34.1%,平均生存时间25个月.其中符合Milan标准的手术患者术后1,2,3年的总体生存率及无瘤生存率分别为:88.4%,72.5%,57.9%及77.6%,62.3%,51.8%,平均生存时间39个月.超出Milan标准的6例患者均在术后1年内出现肿瘤的复发,有2例患者在术后1年内死亡,术后1年生存率为66.7%.其余4例患者于术后2年内相继死亡.平均生存时间14个月.提示原位肝移植是原发性肝癌的有效治疗方法之一,选择符合Milan标准的原发性肝癌患者行肝移植手术治疗将会取得最佳疗效.     

肝癌肝切除后的复发补救性肝移植治疗

背景:在当前供肝紧缺的情况下,补救性肝移植策略的提出为缓解这个问题提供了新的方向.目的:对比符合Milan标准肝癌患者肝切除后复发再行补救性肝移植和直接行肝移植的疗效.方法:选择2001-07/2009-08在解放军南京军区福州总院肝胆外科接受肝移植治疗,符合Milan标准的肝癌患者53例,其中12例符合Milan标准肝切除后复发再行肝移植,作为补救性肝移植组,41例行直接肝移植.结果与结论:补救性肝移植组手术时间、无肝期、术中出血量、术中悬浮红细胞输注量、ICU时间、住院总时间、住院总费用明显高于直接肝移植组(P > 0.05),两组术中冰冻血浆输注量比较差异无显著性意义(P < 0.05).随访39个月,两组总体生存率差异无显著性意义(P > 0.05).说明对于符合Milan标准的肝癌患者首次行肝切除,待其复发再行肝移植也是一种可行的策略.     

进展期胃癌患者术中低渗热灌注化疗临床疗效分析

目的 观察术中腹腔低渗热灌注化疗对进展期胃癌患者术后临床疗效.方法 将施行胃癌根治术88例进展期胃癌患者随机分为低渗热化疗组30例,术中予以腹腔低渗热灌注化疗;等渗热化疗组31例,术中等渗热灌注化疗;对照组27例,术中腹腔不作任何灌注化疗.观察比较三组患者的手术并发症发生率和术后长期生存率.结果 手术并发症发生率三组患者间的差异性无显著性意义(P＞0.05).5年生存率低渗热化疗组64%,等渗热化疗组59%,显著高于对照组32%.但两个热化疗组比较,差异无显著意义(P=0.521),分别与对照组比较,P=0.0085和P=0.0321.低渗热化疗组9例复发,复发时间(24.6±9.7)个月;等渗热化疗组13例复发,复发时间(15.6±8.7)个月;对照组15例复发,复发时间(10.2±5.2)个月.低渗热化疗组复发时间显著晚于对照组和等渗热化疗组,(分别为P=0.0021,P=0.0345),而等渗热化疗组晚于对照组(P=0.0425).结论 低渗热化疗与等渗热化疗均能提高患者的生存率,低渗热化疗在延缓肿瘤复发上优于等渗热化疗.     

进展期肝癌肝移植围手术期辅助性化疗的临床价值

目的:探讨围手术期辅助性化疗对预防进展期肝癌(pTNM分期:Ⅲ、Ⅳa)肝移植术后肝癌复发、提高患者生存率的临床价值,并评价其可行性、安全性。方法:回顾分析2002年4月至2004年10月于我院接受肝移植的25例Ⅲ、Ⅳa期肝癌患者的临床资料,其中12例肝癌患者(化疗组)术前均接受经皮肝动脉栓塞化疗(TACE),术中、术后均采用阿霉素(ADM)+5-氟尿嘧啶(5-Fu)+顺铂(CDDP)方案行全身静脉化疗,以未接受任何辅助化疗的13例患者为对照组(未化疗组),比较两组的肿瘤复发率、累计生存率和无瘤生存率;观察该化疗方案的安全性及副作用。结果:经统计分析,化疗组肿瘤复发率(7/12,58.3%)明显低于未化疗组(11/13,84.6%)(P<0.05)。化疗组和未化疗组1、2年生存率分别为75.0%、58.3%和53.8%、30.7%,两组术后累计生存率比较差异有显著意义(P<0.05);化疗组1、2年无瘤生存率(66.7%、41.6%)亦高于未化疗组(38.5%、15.4%),两者比较差异有显著意义(P<0.05)。化疗组全部患者未出现与化疗相关的肝肾毒性,副反应轻。结论:围手术期辅助性化疗可显著提高进展期肝癌肝...     

肝癌肝移植的临床观察(附16例报告)

【目的】探讨中晚期肝癌肝移植的价值及预后。【方法】对本中心行肝移植及辅助化疗的16例肝癌的临床资料进行回顾性分析。【结果】全部16例患者均顺利渡过围手术期,2例胆管细胞癌分别于术后3个月、6个月肝癌复发。1例原发性肝癌于术后3个月死于颅内转移,另1例术后12月肝癌复发。余12例随访期间均无瘤生存。【结论】肝移植是治疗中晚期肝癌的有效方法之一,术前、术中及术后的序贯化疗,术中严格的“无瘤原则”以及术后免疫抑制剂的合理应用是预防肿瘤复发的有效手段。     

肝癌肝移植术围术期化疗15例护理体会

随着肝移植技术的不断进步,其适应证亦在逐步放宽,除良性终末期肝病、小肝癌外,一些进展期肝癌也可进行肝移植手术。但进展期肝癌移植后容易复发,长期生存率低。Stippel等报道,进展期肝癌3年生存率为34％;Calne等报道5年生存率为18．6％;郑树森等00报道18例肝癌术后复发8例。主要复发时间为术后6～12个月。我科近1年来行经典式原位肝移植术（orthotopic liver transplantation,OLT）,治疗肝癌共15例,其中复发性肝癌8例,均在围术期进行了全身化疗,近期疗效满意,说明肝癌肝移植术后行围术期化疗对降低肝癌肝移植术后复发有重要意义,而做好围术期化疗的护理则是顺利完成化疗方案的重要保证。     

原发性肝癌的治疗方法与术后肿瘤复发和生活质量的关系

[目的]探讨原发性肝癌(PLC)外科治疗方法与患者术后肿瘤复发和生活质量之间的关联性.[方法]根据治疗方式不同,将358例PLC患者分为两组,肝叶切除组(n=308)和肝移植组(n=50).根据肝功能差异,将肝切除病人分为中重度肝硬化组(n=34)、轻度肝硬化组(n=230)和无肝硬化组(n=44).比较两组患者术后生存率、肿瘤复发率和生活质量.[结果]肝叶切除组1、3、5累积生存率和复发率与肝移植组比较差异无显著性(P>0.05);但中重度肝硬化患者3年、5年生存率低于轻度肝硬化、无肝硬化患者;1、3、5累积生复发率高于轻度、无肝硬化患者,且差异有显著性(P<0.01),轻度与无肝硬化患者组间比较差异无显著性(P>0.05).肝叶切除组患者躯体功能(PH)、心理功能(PS)、症状/副作用(ST)、社会功能(SO)、自我评价及总分均低于肝移植组(P<0.01).PLC患者的手术方法、肝硬化程度与肿瘤复发率和患者的生活质量密切相关.[结论]肝叶切除治疗无硬化或轻度肝硬化PLC与肝移植比较其近远期疗效接近,但中重度肝硬化患者行肝叶切除其肿瘤复发率较高,术后生活质量低.     

亚砷酸联合维生素C治疗复发难治性多发性骨髓瘤的疗效观察

目的探讨亚砷酸联合维生素C对复发难治性多发性骨髓瘤的疗效,并与单用亚砷酸治疗进行比较。方法将2008至2011年收治的42例复发难治性多发性骨髓瘤患者随机分为两组:单用亚砷酸组(对照组)、亚砷酸联合维生素C组(联合组),每组患者21例。对照组予亚砷酸10 mg/d静脉滴注,6周一个疗程,其中前4周用药,间歇2周,共5个疗程;联合组在亚砷酸应用过程中加用维生素C 1.0 g/d静脉滴注,余同对照组。所有患者于疗程间歇期口服沙利度胺100 mg/d。结果 (1)联合组患者总有效率63%,明显高于对照组(29%)(P=0.043)。(2)联合组患者中位无进展生存期(PFS)为9.0个月(6.2¹1.8个月),Kaplan-Meier法分析联合组PFS长于对照组(P=0.043);联合组中位总生存期(OS)为14.0个月(11.411.8个月),Kaplan-Meier法分析联合组PFS长于对照组(P=0.043);联合组中位总生存期(OS)为14.0个月(11.4¹6.6个月),Kaplan-Meier法分析联合组OS长于对照组(P=0.038)。(3)联合组各种不良反应与对照组比较均无显著差异(P>0.05)。结论亚砷酸联合维生素C治疗复发难治性多发性骨髓瘤的疗效优于单用亚砷酸。     

Treatment of recurrent hepatocellular carcinoma following liver resection,ablation or liver transplantation

Hepatocellular carcinoma(HCC) is the most common primary liver malignancy and causes one third of cancer related deaths world-wide. Approximately one third of patients with HCC are eligible for curative treatments that include hepatic resection, liver transplantation or imaging guided tumor ablation. Recurrence rates after primary therapy depends on tumor biology and pre-treatment tumor burden with early recurrence rates ranging from 30%-80% following surgical resection and ablation. HCC recurs ...     

Diagnostic accuracy of multi-/single-detector row CT and contrast-enhanced MRI in the detection of hepatocellular carcinomas meeting the milan criteria before liver transplantation

Liver transplantation has been considered to be the only causal treatment for liver cirrhosis patients with hepatocellular carcinoma (HCC) due to its theoretical advantage of eliminating both the tumor and liver disease. However, because of the shortage of donor organs, it is strongly recommended that liver transplantations should be performed on cirrhotic patients with HCCs only when the patients meet the predetermined criteria in terms of number and extent of HCCs. Imaging is thus decisive in the patient inclusion or exclusion from transplantation lists. The imaging techniques used are CT, MRI and ultrasonography. The latter has been proven to be ineffective for HCC surveillance in transplant recipients because of its heavy operator dependence and unreliable detection of small and intermediately sized HCCs. The purpose of this article, then, is to systematically review the diagnostic performances of single-/multidetector row CT, dynamic gadolinium-enhanced MRI, superparamagnetic iron oxide (SPIO)-enhanced MRI and double-contrast MRI using both gadolinium and SPIO for the detection of HCCs with special emphasis on liver transplantation.     

New perspectives and strategy research biomarkers for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Cirrhosis caused by hepatitis B virus, hepatitis C virus or chronic alcohol intake is associated with major risk. Systematic screening for HCC of asymptomatic patients with cirrhosis is needed for earlier detection of small tumors requiring treatment (liver transplantation, surgical resection, percutaneous techniques). The recommended screening strategy among cirrhotic patients is based on regular liver ultrasonography associated with serum alpha-fetoprotein (AFP) assay. As the performance of AFP is not satisfactory, additional tumoral markers are proposed (des-gamma-carboxyprothrombin, glycosylated AFP-L3 fraction). Currently, diagnosis of HCC in cirrhotic patients includes non-invasive tests (imaging after contrast administration, AFP assay); diagnostic biopsy is performed when imaging is limited. After treatment, tumor recurrence is assessed by regular follow-up (AFP assay and imaging). Despite the lack of accurate markers, recent developments in genomic and proteomic approaches will allow the discovery of new biomarkers for primary tumors, as well as for recurrence. This review summarizes the current state of biomarkers for screening, diagnosis and follow-up of HCC, and highlights new perspectives in the field.     

Loco-regional intervention for hepatocellular carcinoma

Anatomic location/size and number of lesions, inadequate volume of future liver remnant, or poor coexisting premorbid conditions preclude surgery in the majority of patients with hepatocellular carcinoma (HCC). Liver transplantation can cure some patients with poor liver function, but few patients are eligible because of scarcity of donors. Without specific anti-cancer treatment, the prognosis of HCC is poor. Various locoregional therapies are used to treat patients who are not candidates for surgery, and have emerged as tools for palliation, tumor down-staging, and bridging therapy prior to liver transplantation. Currently, local ablative therapy even competes with partial hepatectomy and liver transplantation as a primary treatment for small HCC. HCC is well suited to treatment with loco-regional therapy because it has a tendency to stay within the liver, with distant metastasis generally occurring late in the course of disease. This suggests that an effective local-regional therapy can have a great impact on HCC patients who are not candidates for surgical treatment. Loco-regional therapy can further be justified because patients with HCC usually die of liver failure consequent to intrahepatic growth resulting in liver tissue destruction, rather than extrahepatic metastases.     

Achievement of sustained viral response after switching treatment from pegylated interferon α-2b to α-2a and ribavirin in patients with recurrence of hepatitis C virus genotype 1 infection after liver transplantation: a case report

We report a case in which sustained viral response was achieved after switching treatment from pegylated interferon (PEG-IFN) α-2b to α-2a and ribavirin (RBV) in patients with recurrence of hepatitis C virus (HCV) infection after living donor liver transplantation. The patient was a 62-year-old man with liver cirrhosis due to HCV genotype 1b infection. The patient had 8 amino acid (aa) substitutions in the interferon sensitivity-determining region, and had substitutions for mutant and wild-type at aa70 and aa91, respectively, in the core region. The patient had minor genotype (GG) IL28B single nucleotide polymorphisms (rs8099917). He had initially received interferon α-2b and RBV for 2 years, and later developed hepatocellular carcinoma (HCC). After surgical resection of HCC, he subsequently received PEG-IFN α-2b and RBV for 1.5 years, without undetectable viremia during the treatment course. Due to recurrence of HCC, the patient received a living donor liver transplantation. Later on, hepatitis C relapsed. For the management of relapse, he received another course of PEG-IFN α-2b and RBV. However, breakthrough viremia occurred. PEG-IFN was thus switched from α-2b to α-2a and RBV for another 17 months. The patient eventually achieved a sustained viral response.     

肝癌转移复发监测：磁共振扩散加权成像与外周血分子生物学技术研究进展

肝癌（hepatocellular carcinoma,HCC）的治疗方法日趋多样化,对治疗后的随访及监测提出了更高的要求。包括MRS、DWI及PWI在内的功能MRI是一种无创性检测方法,可以从局部及整体了解肝脏的代谢、能量及血流等的变化,其在肝脏显像中的不断发展对评价HCC治疗后的疗效及预后有着深远的意义。HCC转移复发是一个多步骤、多因素相互作用的复杂过程。在HCC转移复发的蛋白质组学研究方面,发现了很多新的潜在分子生物学标记物。由于仅用单个指标无法进行准确预测,采用多个指标进行联合检测将是今后HCC转移预测的研究方向。该文旨在揭示肝脏DWI的原理以及目前在辨别肿瘤生物学特性中的作用,评价HCC对治疗的反应,并探索性地提出了DWI在HCC转移复发监测中的应用前景,综述了所涉及HCC转移复发早诊的外周血新型分子标记物。-     

Skeletal muscle metastases of hepatocellular carcinoma: A case report and literature review

BACKGROUNDThe metastasis of liver cancer to skeletal muscle is extremely rare compared to other sites. We herein report a case of rapidly developing skeletal metastases following liver transplantation due to primary liver cancer.CASE SUMMARYA 70-year-old male with underlying chronic hepatitis B virus infection was diagnosed with hepatocellular carcinoma (HCC), for which he underwent liver transplantation in 2014. Six years after receiving the transplant, pathological examination confirmed the presence of HCC without vascular invasion. He was admitted to the hospital with a rapidly growing mass on his right thigh. Ultrasound examination revealed a mixed echo mass in the lateral soft tissue of the middle part of the right femur. Magnetic resonance imaging showed heterogeneous iso-signal intensity on T1-weighted images and heterogeneous hyper-intensity on T2-weighted images compared to the surrounding muscles. Pathological examination of the ultrasound-guided needle biopsy specimen revealed that it was similar to the previously detected liver cancer; the diagnosis was metastasis of HCC. Surgical excision was performed. There were no other sites of metastasis, and the patient recovered well after surgery.CONCLUSIONThis report presents a rare case of skeletal metastasis following liver transplantation for HCC. The study suggests a possible role for skeletal muscle metastasis mechanisms, which should be the focus of future research.