肝癌肝移植的预后因素分析

背景与目的：肝移植（liver transplantation,LT）是目前治疗肝细胞癌（hepatocellular carcinoma,HCC）最好的措施,但影响HCC肝移植预后的主要因素和手术指征始终存在争议。明确影响预后的主要因素有助于确定合理的手术指征,进而提高HCC肝移植的生存率。本研究旨在探讨影响HCC肝移植预后的主要因素。方法：回顾性分析1999年2月至2004年12月在四川大学华西医院施行肝移植的98例HCC患者的临床资料和随访结果。用Kaplan—Meier法计算全组的累积生存率,log-rank检验做单因素分析,Cox比例风险回归模型进行多因素分析。结果：全组随访1—78个月,中位随访时间37．6个月;随访期间死亡31例（31．6％）,51例复发（52．0％）。全组病例1年、3年和5年累积生存率分别为84．9％、49．3％和33．2％。单因素分析显示,肿瘤大小、门静脉癌栓（portal vein tumor thrombus．PVTT）、AFP水平、pTNM分期和组织学分级与预后有关：Cox回归多因素分析显示,肿瘤大小和PVTT是影响预后的独立因素。结论：肿瘤大小和PVTT是影响HCC肝移植预后的最主要因素。     

Treatment of recurrent hepatocellular carcinoma after liver transplantation

Aim: Liver transplantation (LT) is a curative treatment for localized hepatocellular carcinoma (HCC), but the recurrence rate after LT is about 10–20%, with a dismal prognosis. Little data exist as to the natural history, treatment outcome and optimal treatment of recurrent HCC after LT. We reviewed various treatment modalities given to patients with recurrent HCC after LT. Methods: Among 132 patients who underwent LT for localized HCC, we retrospectively reviewed medical records of 39 of the 132 patients who developed recurrent HCC after LT. We analyzed the clinical outcome of various treatment modalities and treatment‐related adverse events. Results: A total of 39 (29%) of the original 132 patients had recurrent HCC, most recurrences (82%) having occurred within 1 year after LT and involved extrahepatic lesions. Only seven patients had recurrent disease limited to the liver. The median overall survival from the initial treatment of all relapsed patients was 6.9 months. There were various initial treatment modalities, namely palliative systemic chemotherapy, trans‐catheter arterial chemo‐embolization/infusion (TACE/I), radiation therapy (RT), surgical resection and no treatment. The median overall survival was 9.5 months for first‐line chemotherapy, including those who had prior local therapy, 6.3 months TACE/I and 6.9 months for RT. Conclusion: Various clinical approaches have been used to treat patients with recurrent HCC after LT in a clinical setting. More effective strategies and clinical guidelines for recurrent HCC following LT must be established.     

肝移植术后肝癌的介入治疗

目的：观察介入化疗栓塞在肝移植（LT）后肝细胞性肝癌（HCC）复发治疗中的作用。方法：15例原发性HCC肝移植后肿瘤复发且失去外科手术机会的患者接受1次或多次介入化疗栓塞（TACE）治疗。通过影像学资料判定治疗效果,观察患者生存率。结果：15例中2例（13.33%）肿瘤完全消退,10例患者（66.67%）肿瘤体积缩小≥50%。随访期间有11例（73.33%）出现了肝内或肝外新发病灶。移植后1、2和3年生存率分别为86.3%、57.5%和48.5%;复发后0.5、1、1.5、2年生存率分别为70.2%、55.7%、47.2%和38.8%,未出现严重并发症。结论：介入化疗栓塞是肝移植后肝癌复发且失去手术机会的患者可以选择的一种有效、安全的治疗手段,可一定程度地控制肿瘤生长。     

Accelerated growth rates of recurrent hepatocellular carcinoma after liver transplantation.

The growth rates of recurrent hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLTX) were estimated by calculating the tumor doubling time (TDT) in 20 patients. The mean TDT, calculated by multiple measurement of tumor size, was 44.3 +/- 11.3 days (mean +/- standard error) in 12 patients with pulmonary metastasis (range, 10 to 161 days) and 37.6 +/- 8.9 days (range, 7 to 65 days) in 5 patients with liver allograft recurrence. The TDT as estimated by serum alpha-fetoprotein (AFP) levels in 6 patients was 37.3 +/- 10.0 days (range, 12 to 84 days). The mean TDT obtained from 5 control subjects with HCC who were treated with liver resection (without immunosuppression) was 273.8 +/- 79.1 days (range, 82 to 560 days). The disease-free period and survival time after OLTX both correlated well with the TDT (r = 0.546 and r = 0.701, respectively). The patients with fibrolamellar HCC had a greater TDT and a longer survival time than those with nonfibrolamellar HCC. Despite a wide range of TDT in patients who received transplants, their recurrent HCC tumors grew significantly faster than those of patients with the same disease who did not receive transplants. The factors involved in this accelerated growth rate may include the use of immunosuppressive drugs and the consequent suppression of host immunity against the growth of micrometastasis.     

纤维板层型肝癌的影像学表现

目的 观察纤维板层型肝癌（ＦＬ－ＨＣＣ）的影像学表现。方法 １１例ＦＬ－ＨＣ互病理证实。做超声波（ＤＳ）检查１０例,ＣＴ扫描１１例,ＭＲＩ８傲因管造影９例。结果 ＵＳ显示肿瘤呈高回声４例,混杂回声６例,４例有大小不一的囊性区,ＤｏｐｐｌｅｒＵＳ提示肿瘤实性部分血供丰富。ＣＴ显示肿瘤单发９例,多个结节融合２例,平扫均为低密度,７例肿块中心区见放射状更低密度区,病理检查为致密胶原瘢痕,４例见点状钙化,     

肝癌肝移植复发的干预

肝细胞肝癌传统的根治方法是手术切除,应用范围窄,肝移植术为肝癌患者提供了一个理想的根治性治疗方法,但肿瘤的复发和转移往往造成手术失败,因此对于手术而言,把握合理的手术指征是治疗成功的关键,新的化疗药物的发展,以及分子靶向药物的出现和在临床的广泛应用,进一步提升了围手术期全身化疗的作用,结合免疫抑制剂的合理调整,为肝癌根治治疗提供了希望。     

A pleomorphic hepatocellular carcinoma with biochemical features of fibrolamellar hepatocellular carcinoma

A case of pleomorphic hepatocellular carcinoma with biochemical characteristics similar to those of fibrolamellar carcinoma is described. During chemotherapy there was a marked disorder of vitamin B12 metabolism.     

肝癌肝移植术后骨转移的放射治疗及其对预后的影响

目的通过回顾性分析肝细胞肝癌(以下简称肝癌)肝移植后骨转移患者的临床特征、放疗疗效及预后因素,探讨其有效治疗方法。方法 随访853例肝癌患者。其中30例在肝移植后出现骨转移,接受针对骨转移部位放疗,剂量范围8～60 Gy(中位剂量为40 Gy)。用Kaplan-Meier法进行生存分析,单因素分析用Log-rank方法,多因素分析采用Cox回归模型Backward-Wald法。结果 30例患者肝移植后出现骨转移,1年、2年生存率分别为39.7%、24.4%,中位生存时间8.6月。96.7%的患者接受放疗后疼痛缓解(29/30)。放疗剂量在30～60 Gy之间对疼痛的缓解在剂量效应关系上无相关性(P=0.670)。结论 放疗可以缓解肝细胞癌患者肝移植后骨转移的疼痛,从而提高患者的生存质量。     

Outcome of patients with fibrolamellar hepatocellular carcinoma

BACKGROUND: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare variant of hepatocellular carcinoma, has distinct pathologic features, and typically occurs in young patients without underlying hepatitis or cirrhosis. METHODS: Forty-one patients with the pathologic diagnosis of FL-HCC evaluated at our institution between 1986 and 2003 were identified from a prospective database. RESULTS: Median age of all patients was 27 years. None of these patients had underlying hepatitis or cirrhosis, and only 3 (7%) patients had an alpha-fetoprotein level > 200 ng/mL. Twenty-eight patients with primary disease underwent complete gross resection, and 13 patients were unresectable. In patients treated with resection, median tumor size was 9 cm (range, 3-17), 9 (36%) had vascular invasion, and 14 (50%) had lymph node metastases. There were no perioperative deaths. With a median follow-up of 34 months, 5-year overall survival for resected patients was 76%. However, 5-year recurrence-free survival was only 18%, and of the 9 resected patients with more than 5 years of follow-up, 7 had recurrences. Lymph node metastasis was the only significant negative prognostic factor. Seventeen (61%) patients underwent a second operation for recurrent disease. Median survival for unresected patients with FL-HCC was only 12 months, and no patient survived beyond 5 years. CONCLUSIONS: FL-HCC occurs in a distinctly different population of patients than common HCC, and patients with FL-HCC generally fare better after complete resection. These tumors have a relatively indolent tumor biology, and late recurrences are common. Repeat resections for recurrence should be considered given the lack of other effective treatment options.     

肝癌肝移植术后辅助化疗的临床分析

目的探讨晚期肝癌患者肝移植术后辅助化疗的可行性、安全性和疗效。方法分析10例原发性肝癌患者肝移植术后辅助化疗的临床资料。化疗采用FAP方案：四氢叶酸钙(CF)200mg／m^2,5-氟尿嘧啶(5-Fu)500mg/m^2,静脉滴注,第1～5天;阿霉素(ADM)40mg/m^2,顺铂(CDDP)30mg/m^2,静脉滴注第1天。对化疗时机、化疗方案、免疫抑制剂和化疗的协同作用以及化疗药物的副作用进行初步评价。结果10例患者至今存活7例,最长32个月,最短9个月;死亡3例,生存期均超过了1年,其中2例死于术后13个月,1例死于20个月,死亡原因均为肿瘤转移。化疗毒副反应轻。结论肝癌患者肝移植术后辅助化疗是可行的、副作用小,有可能延长患者生存期;选择化疗时间对肿瘤复发和患者生存率可能有影响。     

Recurrent hepatocellular carcinoma after liver transplantation mimicking post‐transplantation lymphoproliferative disorder

Approximately 5% of patients with end‐stage cirrhosis undergoing orthotopic liver transplantation have occult hepatocellular carcinoma. Careful follow up is required to detect recurrent tumour, and knowledge of the patterns of recurrence may avoid diagnostic confusion with other malignancies, such as post‐transplantation lymphoproliferative disorder. This case report illustrates an unusual presentation of recurrent hepatocellular carcinoma in a 56‐year‐old man presenting with a para‐aortic soft tissue mass, thought clinically and radiologically to represent lymphoma or post‐transplantation lymphoproliferative disorder. This case demonstrates that recurrent hepatocellular carcinoma can present late after transplantation as retroperitoneal lymphadenopathy, and should alert physicians and radiologists to be aware of the radiological appearances of recurrence and of the need for early biopsy to avoid diagnostic confusion with other malignancies.     

Impact of ABO-incompatibility on hepatocellular carcinoma recurrence after living donor liver transplantation

BackgroundABO-incompatible (ABO-I) living donor liver transplantation (LDLT) has been reported to have acceptable outcomes in the era of rituximab-based prophylaxis. However, the outcomes of ABO-I LDLT for hepatocellular carcinoma (HCC) remain to be elucidated. This study aimed to clarify the impact of ABO-Incompatibility on oncologic outcomes of LDLT for HCC.MethodsPatients with HCC who underwent ABO-I LDLT were randomly matched by 1:2 ratio to those who underwent ABO-compatible (ABO-C) LDLT according to propensity score. HCC recurrence and patient survival were analyzed using the Kaplan-Meier method and log-rank test.ResultsBetween January 2012 and December 2015, a total of 160 patients underwent LDLT for HCC confirmed by pathology analysis of liver explants. Thirty-nine consecutive patients underwent ABO-I LDLT for HCC, and 78 ABO-C LDLT patients were selected by propensity score matching, which made no significant difference between the two groups in baseline, perioperative, and tumor characteristics. The 1-, 3-, and 5-year recurrence-free survival rates in the ABO-I and ABO-C LDLT groups were 76.9%, 68.5%, 63.6% and 74.4%, 70.5%, 70.5%, respectively (p = 0.77). The site distribution of initial recurrence showed no significant difference between the two groups. The overall survival rates over the same period in the ABO-I and ABO-C LDLT groups were 82.1%, 73.5%, 73.5% and 92.2%, 80.3%, 80.3%, respectively (p = 0.34).ConclusionsABO-I LDLT, having no adverse impact on oncological outcomes, can be a feasible transplant option for HCC.     

Developments in liver transplantation for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a serious health problem worldwide because of its association with hepatitis B and C viruses. In this setting, liver transplantation (LT) has become one of the best treatments since it removes both the tumor and the underlying liver disease. Due to the improvement of imaging techniques and surveillance programs, HCC are being detected earlier at a stage at which effective treatment is feasible. The prerequisite for long term success of LT for HCC depends on tumor load and strict selection criteria with regard to the size and number of tumor nodules. The need to obtain the optimal benefit from the limited number of organs available has prompted the maintenance of selection criteria in order to list only those patients with early HCC who have a better long-term outcome after LT. The indications for LT and organ allocation system led to many controversies around the use of LT in HCC patients. This review aims at giving the latest updated developments in LT for HCC focusing on selection criteria, diagnostic tools, prognostic factors, treatment on the waiting list, role of living donor liver transplantation and adjuvant therapy, and the impact of immunosuppression on HCC recurrence after LT.     

Bone metastases of hepatocellular carcinoma after liver resection.

Between January 1985 and July 1990, 323 cases of hepatocellular carcinoma underwent liver resection in our department. Bone metastases were found in 12 of these cases (3.7%). Bone metastases were mainly found in vertebral bone (58.3%) and pelvic bone (41.7%). The time interval to the development of bone metastasis after liver resection was closely related to the presence of intrahepatic metastasis and the stage at operation. In all cases, the initial clinical symptom was pain and/or motor disturbance. Radiotherapy was performed in 10 cases and transcatheter arterial embolization or surgery was performed in 4 cases. The pain or neurological symptoms improved with these therapies in all cases. Cumulative survival was 1 year in 74%, 2 years in 34%, and 3 years in 17%, respectively.     

Indications and limitations of liver transplantation for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a common cause of cancer-related death worldwide, yet remains difficult to treat, with dismal overall long-term survival rates. Recent strategies using liver transplantation for carefully selected patients with stage I and II HCC and cirrhosis have shown promising results, with 5-year survival rates comparable to survival rates for transplantation patients without malignancy. Currently, however, limited resources and a severe organ shortage make liver transplantation an option for only a limited number of patients with HCC in the United States. Future studies must document the long-term success of this therapy and improve methods for disease control before and after transplantation.