小肝癌的多中心起源与肝移植

近年。随着对早期肝癌及小肝癌的深入研究．肝癌的多中心起源已被证实。既往对小肝癌的治疗以手术切除为首选，却因术后存在较高的复发率而影响手术疗效。术后复发除一部分为原发灶肝内转移外，另一部分实为肝癌的多中心起源。显然，肝癌多中心起源的特性已制约了手术切除在治疗小肝癌的地位。与之相比，肝移植不仅可以去除肿瘤．同时也切除了硬化的肝脏，从而消灭了肿瘤生长的土壤．解决了肝癌多中心起源的问题。由此可见，肝移植将成为治疗小肝癌特别是多中心起源小肝癌的一种趋势。     

Surgical resection versus radiofrequency ablation for small hepatocellular carcinomas within the Milan criteria

Background/Purpose  It has been reported that hepatic resection may be preferable to other modalities for the treatment of small hepatocellular carcinomas (HCCs), by contributing to improved overall and disease-free survival. Ablation techniques such as radiofrequency ablation (RFA) have also been used as therapy for small HCCs; however, few studies have compared the two treatments based on long-term outcomes. The effectiveness of hepatic resection and RFA for small nodular HCCs within the Milan criteria were compared. Methods  A retrospective cohort study was performed with 278 consecutive patients who underwent curative hepatic resection (n = 123) or initial RFA percutaneously (n = 110) or surgically (thoracoscopic-, laparoscopic-, and open-approaches; n = 45) for HCC. The selection criteria for treatment were based on uniform criteria. Mortality related to therapy and 3- and 5-year overall and disease-free survivals were analyzed. Results  The model for endstage liver disease (MELD) scores for all patients in the series were less than 13. There were no therapy-related mortalities in either the hepatic resection or RFA groups. The incidence of death within 1 year after therapy (1.6 and 1.9%, respectively) was similar in the hepatic resection and RFA groups. The group that underwent hepatic resection showed a trend towards better survival (P = 0.06) and showed significantly better disease-free survival (P = 0.02) compared with the RFA group, although differences in liver functional reserve existed. The advantage of hepatic resection was more evident for patients with single tumors and patients with grade A liver damage. In contrast, patients with multinodular tumors survived longer when treated with RFA, regardless of the grade of liver damage. Further analysis showed that surgical RFA could potentially have survival benefits similar to those of hepatic resection for single tumors, and that surgical RFA had the highest efficacy for treating multinodular tumors. Conclusions  In patients with small HCCs within the Milan criteria, hepatic resection should still be employed for those patients with a single tumor and well-preserved liver function. RFA should be chosen for patients with an unresectable single tumor or those with multinodular tumors, regardless of the grade of liver damage. In order to increase long-term oncological control, surgical RFA seems preferable to percutaneous RFA, if the patient’s condition allows them to tolerate surgery.     

Concurrent and subsequent radiofrequency ablation combined with hepatectomy for hepatocellular carcinomas

Partial hepatectomy has long been the standard treatment modality for patients with hepatocellular carcinoma (HCC), although the majority of patients with HCCs are not candidates for curative resection. Radiofrequency ablation (RFA) has been widely used as the preferred locoregional therapy. RFA and hepatectomy can be complementary to each other for the treatment of multifocal HCCs. Combining hepatectomy with RFA permits the removal of larger tumors while simultaneously ablating any smaller residual tumors. By using this combination treatment, more patients might become candidates for curative resection. For treating recurrent tumors involving the liver after hepatectomy, RFA has been performed recently instead of transcatheter arterial chemoembolization or ethanol ablation. Many retrospective studies on the combination of RFA and hepatectomy demonstrate favorable results of effectiveness and safety. However, further investigation of prospective design will be needed to confirm these encouraging results.     

射频消融联合肝动脉插管化疗栓塞治疗原发性小肝癌

目的比较射频消融联合动脉插管化疗栓塞(TACE)和单独射频消融对肝癌的治疗效果.方法对17例肿瘤结节小于3cm的小肝癌病人共23个肝癌结节进行射频消融治疗.其中,12个结节采用射频消融联合TACE治疗.结果联合治疗组平均毁损最大直径(40.8±3.1mm)明显大于单独射频组(37.8±2.8mm)(P＜0.05).随访期间,联合治疗组1例(11.1%)复发,单独射频组1例(12.3%)复发.联合治疗组并发症与单独射频组比较,无明显差异.结论射频消融联合TACE与单独射频治疗比较,可以增加肝癌治疗的效果.     

手术切除联合射频消融治疗多发性肝癌合并肝硬化

目的探讨手术切除联合射频消融(radiofrequencyablation,RFA)治疗多发性肝癌合并肝硬化的可行性及疗效。方法2003年8月~2006年1月我院收治多发性肝癌合并肝硬化18例,术前经超声、螺旋CT或MRI共发现瘤体46个,其中2个病灶10例,3个病灶6例,4个病灶2例,全麻下距瘤体2cm做包括瘤体的不规则肝段切除、次病灶RFA治疗。结果18例均顺利完成手术切除及RFA治疗。同时行胆囊切除术2例,脾切除及食管胃底周围血管离断术1例。手术切除时间(37.4±8.8)min;单个病灶RFA时间(25.6±8.9)min,总RFA时间(39.8±14.7)min;总手术时间(152.6±30.8)min;总术中出血量(465.6±171.0)ml。未出现腹腔出血、胃肠道损伤、膈肌损伤及肝功能衰竭等严重并发症。术后1个月螺旋CT增强扫描证实,18例手术切除边缘未见残余肿瘤组织,RFA治疗病灶均完全坏死。随访6~31个月,5例发现肝内新病灶,采用经皮RFA进行治疗,其中1例术后15个月死于肝内再复发及肺转移;2例分别于术后7、16个月死于肝功能衰竭。结论手术切除联合RFA治疗多发性肝癌合并肝硬化安全可行,近期治疗效果肯定,最大程度保存受损的肝功能,但应根据病灶的位置及肝功能的状况选择合适的病人进行治疗。     

经皮射频微创治疗小肝癌

目的　总结经皮射频消融 (PRFA)治疗肿瘤直径 <5cm小肝癌的疗效和经验。方法　1999年 8月至 2 0 0 2年 6月期间 ,以根治为目的 ,采用PRFA治疗肿瘤直径≤ 5cm的单个原发性肝癌共 84例 ,2 2例结合经皮肝动脉栓塞化疗 ;35例同时行PRFA联合瘤内无水酒精注射术。结果　肿瘤≤ 3cm组 5 5例中第 1年出现肝内复发者 2例 ,死亡 1例 ;第 2年出现肝内复发者 2例 ,死亡 1例。肿瘤大小介于 3～ 5cm组 2 9例中 ,第 1年出现肝内复发者 3例 ,死亡 2例 ;第 2年出现肝内复发者 4例 ,死亡 3例。结论　PRFA为小肝癌治疗提供了一种新的手段 ,经过近 3年技术的提高和经验的积累 ,射频消融完全有可能杀灭肿瘤直径 <5cm的小肝癌 ,达到根治性效果。本组对 84例小肝癌进行以射频消融为主的非手术微创治疗 ,近期疗效满意 ,远期疗效有待进一步随访观察 ,射频消融对小肝癌治疗有着良好的前景。     

腹腔镜射频消融治疗多病灶肝癌的疗效及安全性

目的:探讨腹腔镜射频消融(radiofrequency ablation,RFA)治疗多病灶肝癌的可行性、安全性及疗效。方法:2001年10月-2005年8月,我院对15例多病灶肝癌患者在全麻下进行治疗。其中男12例,女3例,平均(51.5±9.0)岁。术前经超声、螺旋CT或MRI发现瘤体36个,其中2个病灶11例,3个病灶2例,4个病灶2例。肿瘤平均直径(3.1±1.1)cm。乙型肝炎13例,丙型肝炎2例。合并肝硬化13例,胆囊结石2例。结果:15例均顺利完成手术,同时行胆囊切除术2例。单个病灶RFA平均时间(30.2±13.3)min,平均总手术时间(98.7±28.5)min,平均总出血量(145.3±82.8)ml。未出现腹腔出血、胃肠道损伤、膈肌损伤及肝功能衰竭等严重并发症。术后1个月螺旋CT增强扫描证实,病灶完全坏死率达100%。随访12-52个月(平均35个月),1例发现肝内新病灶,3例消融部位复发,均采用经皮射频消融进行治疗。3例分别在术后24、28、36个月死于肝内复发及肝功能衰竭。结论:腹腔镜RFA治疗多病灶肝癌安全可行,近期疗效肯定,最大程度保存了受损的肝功能。但应选择肿瘤位于肝脏表面、肝左外叶或邻近胆囊的病例进行治疗。     

Percutaneous radiofrequency thermal ablation of hepatocellular carcinoma: A safe and effective bridge to liver transplantation

The incidence of hepatocellular carcinoma (HCC) is increasing in the United States. Although liver transplantation is an effective means of treating selected patients, pretransplantation tumor progression may preclude some patients from undergoing transplantation. The aim of this study is to determine the safety and efficacy of percutaneous radiofrequency thermal ablation (RFA) in 33 consecutive patients with nonresectable HCC and advanced cirrhosis. Mean subject age was 57.2 ± 10.6 years, mean Child-Turcotte-Pugh score was 7.0 ± 1.4, and mean maximal tumor diameter was 3.6 ± 1.1 cm. Using contrast-enhanced computed tomography and magnetic resonance imaging, 22 patients (66%) had a complete radiological response at 3 months post-RFA, whereas 11 patients (33%) had an incomplete radiological response. During follow-up, 18 patients (54%) experienced tumor progression and 9 subjects underwent repeated ablation for either residual disease or tumor progression. The overall actuarial patient survival rate of the 33 patients was 58% at 2 years, whereas the transplantation-free patient survival rate was 34% at 2 years. Fifteen of 23 transplant candidates were successfully bridged to liver transplantation after a mean post-RFA follow-up of 7.9 ± 6. 7 months. The extent of tumor necrosis in the explant varied, but no subjects had evidence of tumor seeding on post-RFA imaging, at liver transplantation, or in the explant. The 3-year actuarial posttransplantation patient survival rate was 85%. Two patients have developed posttransplantation recurrence, and both had microscopic vascular invasion in their explants. In summary, our data show that RFA is a safe and effective treatment modality for patients with advanced cirrhosis and nonresectable HCC. Although the ability of RFA to prevent or delay tumor progression requires further prospective study, its favorable safety profile and promising efficacy make it an attractive treatment option for liver transplant candidates with nonresectable HCC. (Liver Transpl 2002;8:1165-1174.)     

肝细胞癌合并肝硬化病人的腹腔镜射频消融治疗

目的探讨肝细胞癌合并肝硬化病人行腹腔镜射频消融(LRFA)治疗的可行性、安全性及疗效。方法2001年8月至2003年12月,25例肝细胞癌合并肝硬化病人在全麻下进行了LRFA治疗。男19例,女6例,平均年龄(52·2±11·9)岁。术前经超声、螺旋CT或MRI等检查共发现瘤体38个,平均肿瘤直径(3·8±1·1)cm。肿瘤均位于肝脏表面、肝左外叶或邻近胆囊等空腔脏器。肝功能均为ChildA或B级。合并慢性结石性胆囊炎3例,糖尿病2例,凝血功能障碍5例。术中行腹腔镜超声检查及病理活检。结果25例病人腹腔镜及术中超声检查共发现瘤体41个。所有病例均顺利完成LRFA治疗,同时行胆囊切除术5例。平均手术时间(72·5±27·6)min。未出现出血、胆道、胃肠道及膈肌损伤等并发症。术后1个月螺旋CT扫描证实,肿瘤完全坏死率达100%。随访6~32个月(平均18个月),1例发现肝内新病灶,3例射频治疗部位复发,l例死于肿瘤复发及肝功能衰竭。结论肝细胞癌合并肝硬化病人行LRFA治疗是安全可行的,可提高肝细胞癌射频消融治疗效果,减少并发症。     

复发性小肝癌再次手术和消融栓塞治疗的探讨

目的：探讨复发性小肝癌的外科治疗方法。
方法：回顾性分析2004年1月—2007年12月第1次手术后复发的小肝癌47例患者的临床资料。分为再次手术组和消融栓塞组,比较两组术后3年生存及复发情况。
结果：再次手术组24例,均行局部切除加肝动脉化疗泵植入行化疗栓塞。消融栓塞组23例,均行局部射频消融治疗加股动脉穿刺肝动脉插管化疗栓塞。再次手术组3年无瘤存活率（66.7%,16/24）高于消融栓塞者（47.8%,11/23）（P＜0.05）,手术切除肿瘤局部复发率（25.0%,6/24）低于消融栓塞（34.8%,8/23）（P＜0.05）。直径<3 cm的肿瘤,采用手术或消融栓塞治疗者3年生存率和复发率差异无统计学意义(P＞0.05)。但3~5 cm肿瘤采用手术治疗者3年生存率高于消融栓塞治疗,复发率低于消融栓塞治疗（均P＜0.05）。
结论：临床医生在为复发性小肝癌患（<3 mm）者提供治疗方案时应当根据患者的具体情况并充分考虑患者意愿。对肿瘤为3~5 mm者则以手术为宜。

     

Effectiveness of radiofrequency ablation for hepatocellular carcinomas larger than 3 cm in diameter

HYPOTHESIS: Radiofrequency ablation is a safe and effective treatment for hepatocellular carcinomas 3.1 to 8.0 cm in diameter. DESIGN: Case series with prospective data collection. SETTING: Tertiary referral center. PATIENTS: Eighty-six patients with hepatocellular carcinoma treated with radiofrequency ablation from May 1, 2001, to December 31, 2002, were placed into categories of those with tumors 3 cm or smaller (group 1, n = 51) and those with tumors 3.1 to 8.0 cm (group 2, n = 35) in diameter. INTERVENTIONS: Radiofrequency ablation was performed with a single or cluster cool-tip electrode. The choice of treatment route was based on tumor size and position. MAIN OUTCOME MEASURES: Complication, treatment mortality, and complete ablation rates. RESULTS: Radiofrequency ablation was performed percutaneously in 26 patients in group 1 and 9 patients in group 2, with laparoscopy in 2 patients in group 1 and 1 patient in group 2, and with open operation in 23 patients in group 1 and 25 patients in group 2. The complication rates were 12% and 17% in group 1 and group 2, respectively (P =.48); treatment mortality rates were 0% and 3%, respectively (P =.41). Complete ablation rates after a single session of ablation assessed by means of computed tomography 1 month after treatment were 94% and 91% in group 1 and group 2, respectively (P =.68). CONCLUSION: Radiofrequency ablation is a safe and effective treatment for patients with hepatocellular carcinomas 3.1 to 8.0 cm in diameter.     

TACE联合RFA与单纯RFA治疗肝细胞癌疗效与安全性比较的Meta分析

目的采用Meta分析评价TACE联合射频消融(RFA)与单纯RFA治疗肝细胞癌(HCC)的疗效及安全性。方法检索2000年1月—2016年11月关于TACE联合RFA与单纯RFA治疗HCC的临床随机对照试验设计的中英文文献,提取纳入研究的信息并行Meta分析。结果共12篇文献入选本研究。Meta分析结果显示,TACE联合RFA组1年、3年总体生存率及1年、3年无瘤生存率均优于单纯RFA治疗组,差异有统计学意义(P均0.05);两组间5年总体生存率差异无统计学意义(P=0.07)。对于肿瘤最大径3cm的HCC,TACE联合RFA组与单纯RFA组1年、3年总体生存率及1年、3年无瘤生存率差异均无统计学意义(P均0.05)。两组间严重并发症发生率差异无统计学意义(P=0.82)。结论 TACE联合RFA治疗HCC的近、中期疗效优于单纯RFA治疗,远期疗效无明显差异。     

肝细胞癌肝移植前介入性干预的研究现状

肝移植是肝细胞癌(HCC)患者最有希望的治疗选择之一。探讨影响HCC肝移植术后生存、预后的问题及对策是现阶段的重要课题。国内外均在尝试用多种围移植术期辅助治疗来降低术后复发和提高生存率，其中以介入性干预方法使用最多，且疗效引人注目。     

Surgical treatment of hepatocellular carcinomas in noncirrhotic liver: Experience with 68 liver resections

Hepatocellular carcinoma (HCC), although generally associated with cirrhosis, can also develop in a noncirrhotic liver. To study HCCs in noncirrhotic liver, their surgical management and prognosis, 68 patients with partial hepatectomy for this disease were analyzed. The liver, in all cases, appeared normal macroscopically at laparotomy, but in 13 cases (19%) it presented some slight histologic modifications, such as steatosis or portal fibrosis. Five patients had a fibrolamellar carcinoma. The mean diameter of the tumors was 8.8 cm. Sixteen patients (23.5%) were treated preoperatively by embolization or chemoembolization. Surgical procedures consisted in a major hepatectomy (three segments or more) in 72% of the cases. Operative mortality and morbidity were, respectively, 2.9% and 19.0%. The 1-, 3-, 5-, and 10-year survivals and the survivals without recurrence were 74%, 52%, 40%, and 26% and 69%, 43%, 33%, and 19%, respectively. Recurrence, which was in most cases intrahepatic, occurred in 39 of the 66 survivors (59%) and was treated by rehepatectomy in 12 cases, providing long survivals. These data justify extensive, aggressive surgery for HCCs in noncirrhotic liver and show the need for long-term follow-up to defect late recurrence, as surgery for recurrent disease prolongs survival.

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Resumen El carcinoma hepatocelular (HCC), aunque generalmente aparece asociado con cirrosis, también puede aparecer en un hígado no cirrótico. Con el propósito de estudiar específicamente el HCC el hígado no cirrótico, su manejo quirúrgico y su pronóstico, se analizaron 68 hepactectomías realizadas para el tratamiento de esta enfermedad. En la totalidad de los casos el hígado apareció macroscópicamente normal en la laparotomía, pero en 13 casos (19%) presentó leves modificaciones histológicas tales como esteatosis o fibrosis portal. Cinco pacientes tenían carcinoma fibrolamelar. El diámetro promedio del tumor fue 8.8 cm. Dieciséis pacientes (23.5%) fueron tratados preoperatoriamente con embolización o con quimioembolización. El procedimiento quirúrgico consistió en hepatectomía mayor (3 segmentos o más) en 72% de los casos. La mortalidad y morbilidad operatorias fueron 2.9% y 19% respectivamente. Las tasas de sobrevida y de sobrevida libre de recurrencia a 3, 5 y 10 años fueron 74%, 52%, 40% y 26%, y 69%, 43%, 33% y 19% respectivamente. La recurrencia, que fundamentalmente fue intrahepática, se presentó en 39 pacientes (59%) y fue tratada con rehepatectomía en 12 casos, lo cual resultó en prolongandas supervivencias. Estos datos justifican la cirugía agresiva y extensa para el tratamiento del HCC en el hígado no cirrótico y demuestran la necesidad de un seguimiento a largo plazo para detectar recurrencias tardías, puesto que la cirugía para la enfermedad recurrente resulta en prolongadas supervivencias.

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Résumé Le carcinome hépatocellulaire (CHC), survenant généralement sur foie cirrhotique, peut également se voir sur foie non cirrhotique. Afin d'étudier la thérapeutique et le pronostic du CHC sur foie non cirrhotique, on a analysé les résultats de 68 pièces d'hépatectomies effectuée pour cette entité. Le foie apparaissait macroscopiquement normal à la laparotomie dans tous les cas, mais dans 13 cas (19%), il y avait des modifications histologiques compatibles avec une stéatose ou une fibrose portale. Cinq patients avaient un carcinome fibrolamellaire. Le diamètre moyen de ces tumeurs était de 8.8 cm. Sieze patients (23.5%) ont été traités préopératoirement par embolisation ou chimioembolisation. Une hépatectomie majeure (plus de trois segments) a été réalisée chez 72% des patients. La mortalité et la morbidité opératoires ont été de 2.9% et de 19%, respectivement. La survie globale et sans récidive à un, trois, cinq et dix ans a été de 74%, 52%, 40% et 26%, et de 69%, 43%, 33% et 19%, respectivement. La récidive, habituellement intrahépatique, a été notée chez 39 (59%) patients, et a été traitée dans 12 cas par une deuxième résection hépatique souvent associée à une survie prolongée. Ces données sont en faveur d'une chirurgie agressive du CHC sur foie non cirrhotique, et démontrent l'intérêt d'une surveillance prolongée car dans certains cas, la récidive est justiciable d'une deuxième chirurgie avec souvent de bons résultats à distance.

     

腹腔镜射频消融治疗肝癌体会

【摘要】〓目的〓探讨腹腔镜下射频消融(LRFA)治疗肝癌的效果。方法〓回顾性分析2010年10月~2013年12月,采用LRFA方法治疗各类肝癌26例,肿瘤位于肝脏Ⅲ、Ⅳ、Ⅴ、Ⅷ段或膈顶以及邻近胆囊胃肠等空腔脏器部位,直径2.2~11.0 cm,单病灶18例,多病灶8例,共39个病灶。肝功能Child A或B级。结果〓26例均顺利完成LRFA治疗,消融时间12~112 min,平均48 min;术后出现腹水2例,胸腔积液1例,无肝衰竭、出血、胆道损伤等并发症。术后1个月B超、CT扫描检查,17例肿瘤不同程度坏死,4例部分液化,5例发现多发病灶及门静脉癌栓消融无效。结论〓LRFA易于操作,并发症少,对特殊部位的肝癌是一种可选择的治疗手段。