不可切除和中晚期肝癌的转化切除

近年来,肝癌的药物治疗取得显著进展,成为中晚期肝癌病人延长生存的重要手段.其中仑伐替尼联合程序性死亡因子1(PD-1)抗体的临床探索在中国非常普遍.部分不可切除或中晚期肝癌病人在接受仑伐替尼联合PD-1抗体治疗的过程中出现肿瘤缩小,从不可切除肝癌转变为可切除肝癌.此文从中国肝癌的现状、不可切除肝癌的转化治疗历史和近年来...     

肝细胞癌肝动脉栓塞化疗降期治疗后根治性切除

目的 探讨肝细胞癌(hepatocellular carcinoma, HCC)经TACE降期治疗后,实施根治性切除的可行性.方法 回顾性分析1991年1月至2002年6月首次诊断为根治性切除困难的HCC,经TACE降期治疗后,成功实施根治性切除患者的临床特点、手术出血量、术后并发症和生存时间.结果 11例HCC患者经TACE治疗后得到降期,成功实施根治性切除.术中平均出血量1336.4ml(110～3200ml),出血量>1000ml者6例.平均手术时间272.8min(210-390min).术后发生胆漏3例,大量腹水1例.中位生存时间为61.5个月,1、2、3年分别有8、7、6例生存.结论 经TACE治疗HCC,可使部分肿瘤降期后再实施根治性切除,其方法安全可行.     

Subtotal hepatectomy following neoadjuvant chemotherapy for a previously unresectable hepatocellular carcinoma

An awareness of variant hepatic vascular anatomy provides vital information in the preoperative evaluation of patients with hepatocellular carcinoma. The authors present a patient with unresectable hepatocellular carcinoma who responded to combination systemic and regional chemotherapy. Because of the presence of an enlarged inferior right hepatic vein, the patient subsequently underwent successful subtotal hepatectomy with resection of all three main hepatic veins. This case illustrates that the combination of innovative neoadjuvant chemotherapy and well-planned surgical approaches may benefit a small number of patients previously deemed unresectable.     

Treatment of unresectable hepatocellular carcinoma with radiolabelled lipiodol

Background: Hepatocellular carcinoma (HCC) is one of the most common solid organ tumours, with approximately 500 000 new cases being reported each year. It has a very high prevalence in Asia, and almost two‐thirds of all cases occur in this region. The incidence of this tumour in Australia has nearly doubled in the past decade. Surgical resection is the mainstay of treatment, but only 10–30% of HCC are amenable to surgical resection at the time of diagnosis. The prognosis for patients with unresectable HCC remains dismal. Internal radiotherapy with radiolabelled lipiodol has been used with some success in treatment of HCC. Several studies have validated its usefulness in an adjuvant setting, but it also appears to have a role in treating unresectable tumours. Methods: Twenty‐two patients with proven HCC, not amenable to or having failed surgical treatment, were evaluated for radiolabelled lipiodol treatment. Of these, 10 patients were excluded after initial evaluation and 12 patients underwent treatment. Patients were followed up every 3 months with physical examination, computed tomography scan and α‐fetoprotein levels. Overall survival, change in tumour size and α‐fetoprotein levels were used to evaluate the efficacy of treatment. Results: The median overall survival in patients undergoing lipiodol therapy was 15 months. Tumour size was stabilized in most patients and very few side‐effects of the treatment were observed. Conclusion: This study has shown that radiolabelled lipiodol is an effective method for the treatment of unresectable locally advanced HCC.     

索拉非尼治疗不可切除肝细胞肝癌疗效观察

目的 观察索拉非尼治疗不可切除肝细胞肝癌的初步疗效和不良反应.方法 选取符合入组标准的不可切除肝癌患者33例,口服索拉非尼,每次400 mg,2次/d,治疗过程中根据不良反应发生情况调整剂量.每6～8周根据修订的RECIST标准评价疗效,并记录不良反应,统计中位疾病进展时间(time to progression,TTP)和中位总生存时间(overall survival,OS).结果 33例患者中没有完全缓解和部分缓解者,疾病稳定11例,疾病进展22例,中位TTP为5.6个月(2.3 ～8.9个月).BCLC B期较BCLC C期的患者中位TTP显著延长;体力状况越差,中位TTP越短;有肝外转移患者的中位TTP明显较无肝外转移患者短.总体不良反应发生率为75.8％,最常见的是手足皮肤反应、腹泻、高血压、皮疹.3级不良反应3例.结论 索拉非尼能延长不可切除肝癌患者的中位疾病进展时间;肿瘤的分期越早,患者的肝功能及体力状况越好,接受索拉非尼治疗获益越好.     

不可切除中晚期肝癌的转化治疗后肝切除术

多数肝癌起病隐匿,早期症状不明显,就诊时往往已属中晚期,预后不佳.转化治疗可使不可切除晚期肝癌病人获得手术治疗机会,并达到R0切除.在转化治疗后,对病人肿瘤、肝脏及其他器官细致全面的评估,将为安全肝切除的术前决策提供依据.转化治疗期间建议采用多学科综合治疗协作组模式定期评估转化治疗效果,并及时制定手术切除方案.     

腹腔镜下治疗不可切除胰腺癌(附10例报道)

目的探讨腹腔镜诊断胰腺癌不可切除之后的微创治疗。方法回顾分析10例腹腔镜诊断胰腺癌不可切除后,进一步经腹腔镜微创治疗肿瘤的技术操作和患者恢复情况。结果3例腹腔镜下胃网膜右动脉置入化疗泵和7例无水乙醇注射均成功,肿瘤区域显影良好,无副损伤和并发症,患者早期恢复顺利。结论腹腔镜下胃网膜右动脉置入化疗泵和注射无水乙醇治疗晚期胰腺癌方法简单可靠,对于腹腔镜诊断胰腺癌不可切除的晚期肿瘤患者提供了微创治疗技术。     

131I lipiodol therapy for unresectable hepatocellular carcinoma

Background : More than 80% of hepatocellular carcinoma tumours (HCC) are unresectable at presentation because of the multicentric nature of the disease or the severity of liver disease. Arterially administered lipiodol is preferentially retained by HCC and has been used as a vehicle for delivery of therapeutic agents to the tumour. The aim of this phase I study is to present the experience with ¹³¹I‐labelled lipiodol in the treatment of unresectable HCC. Methods : ¹³¹Iodine lipiodol treatment was administered to 12 patients with unresectable HCC between 1994 and 1999. The outcome of treatment in these patients was evaluated for survival, clinical tolerance, liver function tests, α‐fetoprotein (AFP) levels and changes in tumour size on computed tomography (CT) scans. Results : Ten of the 12 patients received more than one ¹³¹I treatment. Five patients had treatment for post‐resection recurrence. Serum AFP levels dropped initially in five of the seven patients with elevated values. Tumour size, evaluated by CT scans at 3 months, decreased in six patients and remained stable in the rest, except one patient in whom both the AFP level and tumour size had increased. Using life table analysis, the 50% survival was 19 months. Conclusions : Intra‐arterial ¹³¹I treatment was very well tolerated. A reduction in AFP levels and tumour size occurred in half of the patients and resulted in a 50% probability of survival of 19 months. Further examination of the value of this treatment in phase II and III studies is required.     

A prospective study on downstaging of hepatocellular carcinoma prior to liver transplantation.

In patients with hepatocellular carcinoma (HCC) exceeding conventional (T2) criteria for orthotopic liver transplantation (OLT), the feasibility and outcome following loco-regional therapy intended for tumor downstaging to meet T2 criteria for OLT are unknown. In this first prospective study on downstaging of HCC prior to OLT, the eligibility criteria for enrollment into a downstaging protocol included 1 lesion >5 cm and < or =8 cm, 2 or 3 lesions at least 1 >3 cm but < or =5 cm with total tumor diameter of < or =8 cm, or 4 or 5 nodules all < or =3 cm with total tumor diameter < or =8 cm. Patients were eligible for living-donor liver transplantation (LDLT) if tumors were downstaged to within proposed University of California, San Francisco (UCSF) criteria.13 A minimum follow-up period of 3 months after downstaging was required before cadaveric OLT or LDLT, with imaging studies meeting criteria for successful downstaging. Among the 30 patients enrolled, 21 (70%) met criteria for successful downstaging, including 16 (53%) who had subsequently received OLT (2 with LDLT), and 9 patients (30%) were classified as treatment failures. In the explant of 16 patients who underwent OLT, 7 had complete tumor necrosis, 7 met T2 criteria, but 2 exceeded T2 criteria. No HCC recurrence was observed after a median follow-up of 16 months after OLT. The Kaplan-Meier intention-to-treat survival was 89.3 and 81.8% at 1 and 2 yr, respectively. In conclusion, successful tumor downstaging can be achieved in the majority of carefully selected patients, but longer follow-up is needed to further access the risk of HCC recurrence after OLT.     

晚期不可切除肝癌降期治疗的研究进展

手术切除是原发性肝癌患者获得长期生存预后的主要方法之一,但80%以上的肝癌诊确时已处于进展期而失去早期手术机会。随着肝癌治疗新方法的不断出现,部分晚期肝癌患者可以通过TACE、射频消融、门静脉栓塞、放化疗等方法,将不能进行手术切除的原发性肝癌转变为可手术切除,各种诊疗方案的联合或序贯应用,给晚期肝癌患者带来了希望。本文综述近年来晚期肝癌的降期治疗方法及其研究进展。     

不能切除肝癌不同方式综合治疗的临床分析——附140例

目的 探讨各种非手术治疗方法对不能切除肝癌的治疗效果和获得二期切除率。方法 回顾性分析我科自1987～1997年间收治140例不能一期手术切除的原发性肝癌病例。按不同的外科非手术治疗,分成两大组。观察其二期切除率与1、2、3、5年生存率和中位生存期。结果 单方法组的二期切除率7.32％(6/82),综合治疗组为24.14％(14/58)(P<0.01)。单方法组的1、2、3、5年生存率和中位生存期分别为56.1％、35.4％、17.0％、4.6％,17.19月;多方法组分别为73.7％、57.9％、32.8％、8.8％,26.04月。20例获得二期切除(14.3％),二期切除组的1、2、3、5年生存率和中位生存期分别为95.0％、90％、63.5％、32.9％,46.29月。非二期切除组分别为58.3％、38.3％、17.6％、5.5％,23.47月。结论 不能手术切除肝癌病人经预治疗后,可获二期切除,有助于延长生存期。以化疗栓塞为主的多种方法联合治疗更有效提高二期切除率和延长生存期。     

Salvage surgery for recurrent nasopharyngeal carcinoma.

Objectives: To present our experience of salvage surgery for recurrent nasopharyngeal carcinoma after primary treatment by radiotherapy. Patients and methods: Eleven of 25 patient treated for nasopharyngeal carcinoma between 1990 and 2003 with radiotherapy had either residual or recurrent disease and underwent salvage surgery. The type C infratemporal fossa approach was used to access residual tumor. The patients' progress was followed by clinical examination and interval magnetic resonance scans. Outcome measures and results: The results were analyzed in terms of morbidity and oncological outcome; patients were recorded as NED (no existing disease), AWD (alive with disease), and DOD (died of disease). A disease-free survival rate of 72% was achieved in the salvage surgery group of patients and an overall disease-free survival rate of 56% applied to the initial cohort of 25 patients, following both the single mode and combined treatment. Conclusion: Salvage surgery is feasible for patients with recurrent nasopharyngeal carcinoma and may be achieved with minimal morbidity using the type C infratemporal fossa approach.     

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目的　评估经皮热消融对不能再手术切除的复发性肝细胞癌 (RHCC)的临床治疗价值。方法　 1997年 10月至 2 0 0 2年 12月中山大学附属第一医院采用超声引导经皮射频消融 (RFA)或微波消融 (MWA)治疗不能再手术切除的RHCC ,35例共 87个肿瘤结节 ,直径 0 9～ 6 4cm。观察局部疗效、治疗并发症和远期生存情况。结果　肿瘤完全消融率 (完全灭活率 )为 97 7% (85 / 87) ,其中直径≤ 3cm结节为 98 6 %、3cm以上者为 94 1%。无治疗死亡 ,并发症发生率为 2 9% (1/ 35 )。平均随访 (2 7 7± 16 7)个月 ,肿瘤局部复发率为 10 6 % (9/ 85 ) ;远处复发率为 91 4 % (32 / 35 ) ,其中 15例 (4 7% )发生多次远处复发。经对局部复发和远处复发者的反复治疗 ,首次消融后 1、3、5年累积生存率分别为 77 1%、4 6 2 %和 14 9% ,中位生存期为 2 5 2个月 ;首次肝切除后 1、3、5及 10年生存率分别达到 96 2 %、6 4 1%、4 7 7%和 14 1% ,中位生存期为 5 7 0个月。结论　经皮热消融技术局部灭瘤效果满意 ,创伤微小且便于反复施行 ,能够显著改善病人的远期生存 ,是不能再切除的RHCC有效治疗手段。     

Salvage surgery after definitive chemoradiation for esophageal carcinoma

Definitive chemoradiation has become an effective modality for the treatment of advanced esophageal carcinoma, although local residual lesions or recurrence are detected in more than 50% of patients. For those patients, resection is the only salvage therapy. More than 40% of patients who undergo complete resection survive. After chemoradiation for esophageal carcinoma, severe adhesions may develop between the primary lesion and surrounding vital organs, leading to difficulty in R0 resection. Systemic function including the lungs, heart, and bone marrow could be also severely impaired. This may result in many severe complications after salvage surgery, such as airway necrosis or mediastinitis. To reduce complications, we restrict lymph node dissection, conserve the right bronchial artery, and reconstruct with a gastric tube through the poststernal course. It is also important to modify the method in each case. The more patients select chemoradiation for curative therapy of esophageal carcinoma, the more salvage surgery is needed. Surgeons should consider the indications and techniques for esophageal surgery to increase cure rates and decrease morbidity.     

晚期不可切除肝癌免疫联合治疗相关进展

晚期不可切除肝癌免疫联合治疗方案的临床试验近期相继获得成功(Imbrave150、Keynote524),显著提高了晚期不可切除肝癌的客观反应率与中位生存期,为后续肝癌外科治疗的介入提供了巨大的潜力与现实性。最近,免疫联合治疗的热点问题有：联合治疗方案该如何选择、围手术期应如何使用以及肿瘤免疫微环境、免疫治疗有效的生物...     

中晚期肝细胞癌介入治疗的循证研究

目的Meta-分析不可切除肝细胞癌采用介入化疗栓塞(TACE)治疗的疗效。方法采用关键词“hapatocellular carcinoma”,“liver cell carcinoma”,“randomized controlled trail [RCT]”和“chemoembolization”,对MEDLINE及CNKI中文数据库进行检索,时间为1990—2003年,采用手工检索予以补充。所有13个RCT,都采用Meta分析整合数据。结果TACE治疗能显著增加总体的1及2年生存率(OR：0．54;95％CI：0．33,0．89;P=0．015)。采用栓塞(TAE)治疗的病人的生存率显著高于那些采用经动脉灌注化疗(TAC)的生存率(OR：0．72;95％CI：0．53,0．98;P=0．039)。结论与对症治疗相比,采用TACE治疗肝癌,能显著增加中晚期病人的1及2年生存率,治疗的关键在于术中栓塞。     

Preoperative systemic chemoimmunotherapy and sequential resection for unresectable hepatocellular carcinoma

OBJECTIVE: To examine the surgical and pathologic findings of 15 patients who had initially unresectable hepatocellular carcinoma (HCC) and received preoperative systemic chemoimmunotherapy and sequential resection. SUMMARY BACKGROUND DATA: More than 80% of patients with HCC present for treatment at an unresectable stage. Conventional treatment has produced a low tumor response rate in this group of patients. Recently, new systemic chemoimmunotherapy has been found to be effective and able to make previously unresectable HCC resectable. Sequential resection after response to chemoimmunotherapy could therefore induce complete clinical remission. METHODS: From July 1996 to February 1999, 150 patients with unresectable HCC were treated with systemic chemoimmunotherapy consisting of cisplatin, alpha-interferon, doxorubicin, and 5-fluorouracil for a maximum of six cycles. The residual tumors were reassessed for resectability after treatment aiming at complete remission in the patients after combined modality treatment. Twenty-seven patients had a more than 50% regression in tumor size (2 complete remissions, 25 partial remissions). Fifteen patients had resectable disease after treatment, and all underwent sequential resection with curative intent. Treatment outcome and the surgical and pathologic features of these 15 patients were studied. RESULTS: Fifteen of 150 patients responded to chemoimmunotherapy and underwent sequential resection. They were considered to have unresectable disease as a result of extensive local disease (with and without major vascular involvement) in 10 patients and the presence of extrahepatic or metastatic disease in 5 patients. All patients except two were hepatitis B carriers. Surgical resection of the residual lesion after chemoimmunotherapy was successful for all patients. Eight of the patients had complete pathologic remission. The rest had minimal residual disease (<5%) only. All 15 patients entered complete clinical remission after surgery. Thirteen patients were still alive as of this writing and two had died of recurrent disease. The 1-, 2-, and 3-year survival rates were 100%, 100%, and 53%, respectively. The mean follow-up period was 27 months (range 15-37). Neither the median disease-free nor overall survival had been reached. Ten patients remained in complete remission as of this writing. CONCLUSION: Combined modalities with systemic chemoimmunotherapy and surgical resection can achieve complete clinical remission and long-term control of disease in patients with unresectable HCC.     

TACE联合索拉非尼治疗不可手术切除的肝癌

目的观察TACE联合索拉非尼治疗不可切除肝细胞肝癌(HCC)的有效性和安全性。方法 36例诊断为不能手术切除HCC患者接受TACE联合索拉非尼治疗,每4周随访肝肾功能、甲胎蛋白水平,以mRECIST标准评价肿瘤疗效、记录不良反应发生情况。主要研究终点为联合治疗后总体生存时间(OS),次要研究终点包括联合治疗至疾病进展时间(TTP)、客观反应率(ORR)、疾病控制率(DCR)、安全性。结果本组联合治疗后中位OS 12.5个月,中位TTP 8个月。Child-Pugh分级A级的患者中位OS 15个月、B级的患者中位OS 10个月(2χ=0.07,P=0.05);肝脏单发病灶患者中位OS 18个月、多发病灶患者中位OS 10个月(2χ=4.16,P=0.04)。联合治疗后无完全缓解病例,部分缓解2例,疾病稳定10例,疾病进展24例,ORR 5.56%(2/36),DCR 33.33%(12/36)。主要不良反应为手足皮肤反应和腹泻。联合治疗前平均TACE次数3.3次,间隔时间平均45天,联合治疗后平均TACE次数2.1次,平均间隔120天。结论 TACE联合索拉非尼有助于延长晚期HCC的总体生存时间,尤其对于肝脏单发病灶及肝功能良好的患者。