Liver resection versus liver transplantation for hepatocellular carcinoma within Milan criteria: a meta-analysis of 18,421 patients

BackgroundOutcomes after liver resection (LR) and liver transplantation (LT) for hepatocellular carcinoma (HCC) are heterogenous and may vary by region, over time periods and disease burden. We aimed to compare overall survival (OS) and disease-free survival (DFS) between LT versus LR for HCC within the Milan criteria.MethodsTwo authors independently searched Medline and Embase databases for studies comparing survival after LT and LR for patients with HCC meeting the Milan criteria. Meta-analyses and metaregression were conducted using random-effects models.ResultsWe screened 2,278 studies and included 35 studies with 18,421 patients. LR was associated with poorer OS [hazard ratio (HR) =1.44; 95% confidence interval (CI): 1.14–1.81; P<0.01] and DFS (HR =2.71; 95% CI: 2.23–3.28; P<0.01) compared to LT, with similar findings among intention-to-treat (ITT) studies. In uninodular disease, OS in LR was comparable to LT (P=0.13) but DFS remained poorer (HR =2.95; 95% CI: 2.30–3.79; P<0.01). By region, LR had poorer OS versus LT in North America and Europe (P≤0.01), but not Asia (P=0.25). LR had inferior survival versus LT in studies completed before 2010 (P=0.01), but not after 2010 (P=0.12). Cohorts that underwent enhanced surveillance had comparable OS after LT and LR (P=0.33), but cohorts undergoing usual surveillance had worse OS after LR (HR =1.95; 95% CI: 1.24–3.07; P<0.01).ConclusionsMortality after LR for HCC is nearly 50% higher compared to LT. Survival between LR and LT were similar in uninodular disease. The risk of recurrence after LR is threefold that of LT.     

Liver transplantation for hepatocellular carcinoma: a proposal of a prognostic scoring system

BACKGROUND: The current staging system of hepatocellular carcinoma established by the International Union Against Cancer and the American Joint Committee on Cancer does not necessarily predict the outcomes after hepatic resection or transplantation. STUDY DESIGN: Various clinical and pathologic risk factors for tumor recurrence were examined on 344 consecutive patients who received hepatic transplantation in the presence of nonfibrolamellar hepatocellular carcinoma to establish a reliable risk scoring system. RESULTS: Multivariate analysis identified three factors as independently significant poor prognosticators: 1) bilobarly distributed tumors, 2) size of the greatest tumor (2 to 5 cm and > 5 cm), and 3) vascular invasion (microscopic and macroscopic). Prognostic risk score (PRS) of each patient was calculated from the relative risks of multivariate analysis. The patients were grouped into five grades of tumor recurrence risk: grade 1: PRS = 0 to < 7.5; grade 2: PRS = 7.5 to < or = 11.0; grade 3: PRS > 11.0 to 15.0; grade 4: PRS > or = 15.0; and grade 5: positive node, metastasis, or margin. The proposed PRS system correlated extremely well with tumor-free survival after liver transplantation (100%, 61%, 40%, 5%, and 0%, from grades 1 to 5, respectively, at 5 years), but current pTNM staging did not. CONCLUSIONS: 1) Patients with grades 1 and 2 are effectively treated with liver transplantation, 2) patients with grades 4 and 5 are poor candidates for liver transplantation, and 3) patients with grade 1 do not benefit from adjuvant chemotherapy.     

Second hepatic resection for recurrent hepatocellular carcinoma

During the last 5 years, radical hepatic resection was performed in 91 patients with hepatocellular carcinoma (HCC). Thirty-one of them had tumour recurrence in the remaining liver during the follow-up period. Second hepatic resection was carried out on nine of them 4-38 months after the first hepatectomy. The ages of these patients ranged from 39 to 65 years with an average of 53.7. There were six men and three women. Eight patients had underlying cirrhosis of the liver and one chronic active hepatitis. Six patients are alive, four being free of HCC and two with disease, for 15-45 months after the first operation. Two patients died of systemic cancer dissemination. The remaining patient had tumour recurrence in the liver again and died of hepatic failure after the third laparotomy. The survival rate of these nine patients was significantly better than that of twenty-two patients who were treated by other palliative methods. The present result shows that a second hepatic resection is a possible and meaningful method of treatment for the patients with recurrent HCCs in the liver remnant.     

Liver resection for hepatocellular carcinoma in octogenarians

BACKGROUND: Liver resection is risky in patients aged > or = 80 years. Because of short life expectancies and improved nonoperative modalities, the role of liver resection in octogenarians with hepatocellular carcinoma (HCC) is unclear. METHODS: A retrospective review of the operative results of 260 patients with HCC between 1991 and 1997 was performed. According to the age at the time of operation, these patients were divided into 2 groups. Group 1 comprised 21 patients aged > or = 80 years, and group 2 comprised the other 239 younger patients. The backgrounds, pathologic features of the tumor, and operative results of the patients were compared. RESULTS: Octogenarians had a higher incidence of associated medical diseases, a higher incidence of negative serum hepatitis B surface antigen, a lower alpha-fetoprotein level, and a higher indocyanine green retention rate. Although octogenarians had a longer postoperative hospital stay, there were no significant differences between the 2 groups regarding operative morbidity and mortality. The 5-year disease-free and actuarial survival rates for octogenarians and younger patients were 50.6% and 35.3% (P = .15) and 40.9% and 59.3% (P = .46), respectively. CONCLUSION: Under meticulous preoperative assessments and postoperative care, liver resection for HCC is justified in selected octogenarians, with short- and long-term results comparable to those of younger patients.     

Liver transplantation for recurrent hepatocellular carcinoma in Europe

Abstract. Background: Patient death after liver resection for hepatocellular carcinoma in cirrhosis is caused by tumor recurrence as well as by complications of cirrhosis. Liver transplantation represents the only simultaneous treatment of tumor and primary liver disease. Certain criteria regarding the number (up to three) and size (up to 5 cm) of tumor nodules have to be observed in order to ensure a low risk of extrahepatic spread or vascular infiltration. Liver transplantation, as treatment for recurrent hepatocellular carcinoma, has to observe the same rules. Only few patients have undergone liver transplantation for recurrent hepatocellular carcinoma in cirrhosis. The reason for this restraint is not fully evident. Poor survival rates after liver transplantation as therapy for advanced hepatocellular carcinoma in the 1980s and an increasing shortage of donor grafts are certainly two factors. Methods: We report on two cases from our experience and review the European literature. Results: Outcome in a few selected patients has been rather favorable, despite varying approaches. Conclusions: The only conclusion that can be drawn is that tumor control by liver transplantation is possible in individual patients suffering from recurrent hepatocellular carcinoma. Adult living donor liver transplantation is one way to overcome graft shortage. Other strategies, for example, salvage transplantation, are presented. Received: April 20, 2001 / Accepted: May 11, 2001     

Liver resection for hepatocellular carcinoma in cirrhotic patients

The incidence of hepatocellular carcinoma (HCC) in cirrhotic patients is increasing. Despite advances in imaging and laboratory screening which allow earlier diagnosis, the surgeon is all too often confronted with an HCC of advanced stage or arising in the setting of severe cirrhosis. Hepatic resection is still considered the treatment of choice for hepatocellular carcinoma in patients with liver cirrhosis. From 1998 to 2005, 6 patients (5 males, 1 female, age 52-70 years, mean age 64.1 years) with HCC associated severe, but well compensated liver cirrhosis (Child A-- 4 patients, Child B--2 patients) underwent 9 hepatic resection in our department. Mean tumor size was 56 mm (range 23-86 mm). Two of these lesions were in the left liver and four in the right lobe. Doppler ultrasonography was performed in all cases and CT in 3 cases to confirm the extension of the lesions. Laparoscopy was performed in 3 patients under CO2 pneumoperitoneum. The Pringle maneuver was not used. The transection of the liver parenchyma was obtained by the use of Ligasure and harmonic scalpel. Nine hepatic resections were performed: 7 segmentectomy and 2 non-anatomical resections. The resection margin was 1 cm. The mean operative time was 90 minutes (range 60-120). Mean blood loss was 250 ml and 2 patients required blood transfusion. One patient died on the tenth postoperative day from a severe respiratory distress syndrome and hepatic failure. Major morbidities occurred in three patients who developed moderate postoperative ascites, which resolved successfully with conservative treatment in two patients. Limited liver resection in cirrhotic patients with HCC is feasible with a low complication rate when careful selection criteria are followed (tumor size smaller than 8 cm, Child-Pugh A class and the good general conditions of the patients). Other medical and interventional treatments (chemoembolization, chemotherapy) can only slow the progress of HCC.     

复发性肝癌的腹腔镜再切除

目的探讨腹腔镜肝切除术(LH)治疗复发性肝癌的安全性及可行性。方法 2003年8月至2008年5月,同一手术组完成大约500例肝癌切除手术,其中LH120例。500例患者中,约有100例复发,我们仔细选择6例病例进行了腹腔镜复发性肝癌再切除术,手术适应证评估指标包括肿瘤位置、大小、转移范围、血管侵犯与否以及肝功能状况等。手术方式包括4例局部切除及2例解剖性左外叶切除。对病例资料进行回顾性分析。结果 6例手术均取得成功,无严重术中及术后并发症发生。平均手术时间为(140.8±35.7)min,平均出血量为(283.3±256.3)ml,术后平均住院日为(5.7±1.6)d。结论对于严格选择的病例,LH是治疗复发性肝细胞癌的一种安全有效的方法,具有创伤小、恢复快的优点。     

原发性肝癌肝切除术后复发患者的肝移植治疗

目的观察肝移植治疗原发性肝癌肝切除术后复发患者的疗效。方法回顾性分析11例原发性肝癌肝切除术后复发接受经典原位肝移植治疗的受者的临床资料,观察移植效果。结果在围手术期,1例术后发生移植肝功能不全和凝血功能障碍并发肾功能衰竭死亡;1例术后出现急性胰腺炎,给予生长抑素治疗10d缓解;2例发生急性排斥反应,行大剂量甲泼尼龙冲击治疗3d逆转。10例受者顺利出院。出院后,3例分别于术后第5个月、第7个月、第19个月死于肝癌复发,1、2年受者存活率分别为72．7％（8／11）和63．6％（7／11）,至今最长存活的1例已达4年余。获长期存活的受者肝癌肝切除术前原发病均为小肝癌,肝切除术后复发行肝移植时肝癌均符合Milan标准。结论小肝癌行肝癌肝切除术后应密切随访,如发现肝癌复发且符合Milan标准可考虑行肝移植治疗,患者仍有可能获较长时间生存。     

肝切除治疗原发性肝癌自发性破裂

目的　探讨肝切除治疗原发性肝癌自发性破裂 (简称肝癌破裂 )的作用。方法　分析两所医院 1970年以来采用肝切除术治疗肝癌破裂 2 1例的临床资料。结果　本组男 17例 ,女 4例。平均年龄 4 2 (2 2～ 6 5 )岁。 19例为急症肝切除 ,2例为 2期切除 ,包括左外叶切除 8例 ,左内叶切除 2例 ,左半肝切除 2例 ,右肝部分切除 5例 ,肿瘤切除 4例。本组中Child Paugh肝功能分级A级的 15例 ,B级 6例 ,B级中 1例术后死于肝衰 ,手术死亡率 4 8%。 2 0例生存者 18例获得随访 ,中位生存时间 16个月 ,1,3,5年生存率分别为 6 4 7% ,11 8% ,5 9%。其中 1例已无瘤生存 2 5年 9个月。结论　肝切除是治疗肝癌破裂的最好方法 ,当有可能时应争取施行。肝切除治疗肝癌破裂可能使病人获得长时间生存。     

Liver resection for hepatocellular carcinoma in patients without cirrhosis

Background:

Data on liver resection for hepatocellular carcinoma (HCC) without cirrhosis are sparse. The present study was conducted to evaluate the indications and results of liver resection for HCC with regard to safety and efficacy.

Methods:

Data for patients who had liver resection for HCC without cirrhosis between January 1996 and March 2011 were retrieved retrospectively using a prospective database containing information on all patients who underwent hepatectomy for HCC. Patient and tumour characteristics were analysed for influence on overall and disease‐free survival to identify prognostic factors by univariable and multivariable analysis.

Results:

The 1‐, 3‐ and 5‐year overall survival rates after resection with curative intent for HCC without cirrhosis were 84, 66 and 50 per cent respectively. Disease‐free survival rates were 69, 53 and 42 per cent respectively. The 90‐day mortality rate was 4·5 per cent (5 of 110 patients). Surgical radicality and growth pattern of the tumour were independent prognostic factors for overall survival. Disease‐free survival after resection with curative intent was independently affected by growth pattern and by the number and size of tumour nodules.

Conclusion:

Liver resection for HCC without cirrhosis carries a low perioperative risk and excellent long‐term outcome if radical resection is achieved. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.     

Liver resection for hepatocellular carcinoma in patients with cirrhosis

BACKGROUND: Although liver resection is now a safe procedure, its role for hepatocellular carcinoma (HCC) in patients with cirrhosis remains controversial. METHODS: This study compared the results of liver resection for HCC in patients with cirrhosis over two time intervals. One hundred and sixty-one patients had resection during period 1 (1991-1996) and 265 in period 2 (1997-2002). Early and long-term results after liver resection in the two periods were compared, and clinicopathological characteristics that influenced survival were identified. RESULTS: Tumour size was smaller, indocyanine green retention rate was higher, patients were older and a greater proportion of patients were asymptomatic in period 2 than period 1. Operative blood loss, need for blood transfusion, operative mortality rate, postoperative hospital stay and total hospital costs were significantly reduced in period 2. The 5-year disease-free survival rates were 28.2 and 33.9 per cent in periods 1 and 2 respectively (P = 0.042), and 5-year overall survival rates were 45.9 and 61.2 per cent (P < 0.001). Multivariate analysis identified serum alpha-fetoprotein level, need for blood transfusion and Union Internacional Contra la Cancrum tumour node metastasis stage as independent determinants of disease-free and overall survival. CONCLUSION: The results of liver resection for HCC in patients with cirrhosis improved over time. Liver resection remains a good treatment option in selected patients with HCC arising from a cirrhotic liver.     

The indication of hepatic resection from medical imaging technique for hepatocellular carcinoma

Recently small hepatocellular carcinoma are frequently diagnosed due to the improvement of medical imaging techniques. Main tumors including one with diameter of 1 cm were definitely diagnosed by the combined use of US and CT. US and angiographic examination were useful in definitely detecting tumor emboli in the main trunk even to the subsegmental level of the portal vein. All of the 12 daughter nodules of diameter over 1 cm could be definitely diagnosed by any examinations. However, diagnostic accuracy was in detecting 11 daughter nodules of diameter below 1 cm as the following data shown; one was positive using US, six were positive using CT, and three were positive using angiography. Sequential moving scan technique during the late phase could make definite preoperative diagnosis of small daughter nodule of diameter below 1 cm. Owing to the improvement of the imaging diagnostic technique, we can obtain accurate preoperative information concerning the presence or absence of daughter nodule and tumor emboli in the portal vein. Therefore, we can select suitable candidates for surgical excision or other combined therapy.     

Liver transplantation for hepatocellular carcinoma: further considerations on selection criteria.

The selection criteria in liver transplantation for HCC are a matter of debate. We reviewed our series, comparing two periods: before and after 1996, when we started to apply the Milan criteria. The study population was composed of patients with a preoperative diagnosis of HCC, confirmed by the pathological report and with a survival of >1 year. Preoperative staging as revealed by radiological imagining was distinguished from postoperative data, including the variable of tumor volume. After 1996 tumor recurrences significantly decreased (6 out of 15 cases, 40% vs. 3 out of 48, 6.3%, P < .005) and 5-year patient survival improved (42% vs. 83%, P < .005). Not meeting the Milan criteria was significantly related to higher recurrence rate (37.5% vs. 12.7%, P < .05) and to lower 5-year patient survival (38% vs. 78%, P < .005%) in the preoperative analysis, but not in the postoperative one. The alfa-fetoprotein level of more than 30 ng/dL and the preoperative tumor volume of more than 28 cm3 predicted HCC recurrences in the univariate and mutivariate analysis (P < .005 and P < .05, respectively). The ROC curve showed a linear correlation between preoperative tumor volume and HCC recurrence. Milan criteria significantly reduced tumor recurrences after liver transplantation, improving long-term survival. In conclusion, the efficacy of tumor selection criteria must be analyzed with the use of preoperative data, to avoid bias of the postoperative evaluation. Tumor volume and alfa-fetoprotein level may improve the selection of patients.     

Selection criteria for repeat hepatectomy in patients with recurrent hepatocellular carcinoma

OBJECTIVE: The purpose of this study was to evaluate prognostic factors in patients with recurrence after curative resection of hepatocellular carcinoma (HCC) and to identify selection criteria for repeat resection. SUMMARY BACKGROUND DATA: Recent studies have demonstrated that repeat hepatectomy is effective for treating intrahepatic recurrent HCC in selected patients. However, the prognostic factors in these patients have not been fully evaluated. METHODS: From October 1994 to December 2000, 334 patients underwent primary resection for HCC, and 67 received a 2nd hepatectomy for recurrent HCC. The survival results in these 67 patients were analyzed, and prognostic factors were determined using 38 clinicopathological variables. The prognosis and operative risk in 11 and 6 patients who received a 3rd and 4th resection were also evaluated. RESULTS: The overall 1-, 3-, and 5-year survival rates of the 334 patients after primary hepatectomy were 94%, 75%, and 56%, while those of the 67 patients after a 2nd resection were 93%, 70%, and 56%, respectively. There was no difference in survival (P = 0.64). All of the patients who underwent a 3rd or 4th are currently alive at a median follow-up of 2.5 and 1.4 years, respectively. The operative time and blood loss in the 2nd resection in patients who underwent a major primary resection were not different from those in patients who underwent minor hepatectomy at the 1st resection, and there were also no differences in these variables among the 2nd, 3rd, and 4th resections. In a multivariate analysis, absence of portal invasion at the 2nd resection (P = 0.01), single HCC at primary hepatectomy (P = 0.01), and a disease-free interval of 1 year or more after primary hepatectomy (P = 0.02) were independent prognostic factors after the 2nd resection. Twenty-nine patients with all 3 of these factors showed 3- and 5-year survival rates of 100% and 86%, respectively, after the 2nd resection. CONCLUSIONS: Repeat hepatic resection is the treatment of choice for patients who have previously undergone resection of a single HCC at the primary resection and in whom recurrence developed after a disease-free interval of 1 year or more and the recurrent tumor had no portal invasion.     

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 surgical treatment for recurrent hepatocellular carcinoma after hepatic resection

From 1978 to 1989, 164 patients underwent hepatic resection for hepatocellular carcinoma at our institution. The carcinoma was resected completely in 149 patients. Sixteen patients were excluded from this study because it was not known whether they were recurrent or disease free, or because death occurred as a result of surgical complications. Recurrent disease occurred in 48.1% of the remaining 133 patients. Fifty-seven patients had recurrent tumor only in the residual liver. A second hepatic resection was performed in 14 cases, 22 received intraarterial chemotherapy and/or arterial embolization without resection, and the remaining 21 received no anticancer therapy. The 5-year survival rate of patients who had a second resection was 92.0%. Recurrences in distant organs occurred in 14 patients, and the recurrent carcinoma was resected in five cases. Four of these 5 patients survived more than 3 years after the second surgery. Aggressive surgical resection of recurrent HCC, even for distant metastasis, is a viable approach, and may produce long-term survivors.

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Resumen Ciento sesenta y cuatro pacientes fueron sometidos a resecciôn hepática por carcinoma hepatocelular en el período entre 1978 y 1989 en nuestra instituciôn. La resección del tumor fue completa en 149 pacientes. Dieciseis fueron excluídos del estudio porque en el seguimiento no se pudo establecer si se encontraban con tumor recurrente o libres de enfermedad, o porque los pacientes murieron en el hospital como consecuencia de complicaciones operatorias en el primer mes después de la cirugía.Se présentó enfermedad recurrente en 48.1% de los 133 pacientes restantes; 57 pacientes presentaron el tumor recurrente en el parenquima hepático residual sólamente, y se practicó una segunda resección hepática en 14; 22 recibieron quimioterapia intra-arterial y/o embolización arterial sin resección y los 21 restantes no recibieron quimioterapia antitumoral. La tasa de sobrevida a 5 años de los pacientes sometidos a una segunda resección fué 92%.Se presentó recurrencia en órganos distantes en 14 pacientes, y el tumor recurrente fue resecado en cinco. Cuatro de los cinco sobreviven más de 3 anos después de la segunda resección. La resección agresiva del carcinoma hepatocelular recurrente es un aproche viable, aún en el caso de metástasis distantes, y puede dar lugar a prolongadas superviviencias.

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Résumé Entre 1978 et 1989, 164 patients ont eu une résection hépatique pour carcinome hépatocellulaire. La résection a été considérée comme totale chez 149 patients. Après exclusion de 16 patients soit parce que leur état (récidive ou sans maladie) n'était pas connu soit parce qu'ils étaient décédés pendant leur hospitalisation en raison de complications postopératoires, une récidive a été constatée chez 48.1% des 133 patients restants. Parmi ceux-ci, 57 ont eu une récidive du parenchyme seul. Une deuxième résection a été pratiquée chez 14, une chimiothérapie intra-artérielle et/ou embolisation artérielle sans résection chez 22 alors que les 21 autres patients n'ont pas eu de traitement anticancéreux. La survie à 5 ans des patients qui ont eu une deuxième résection a été de 92.0%. La récidive a touché un autre organe chez 14 patients et s'est prêtée à une deuxième résection dans cinq cas. Quatre de ces cinq patients ont survécu plus de trois ans après cette chirurgie secondaire. Une attitude chirurgicale aggressive de la récidive de carcinome hépatocellulaire, même en cas de métastases à distance, est valable et dans quelques cas, une survie prolongée peut se voir.