Influence of coexisting cirrhosis on outcomes after partial hepatic resection for hepatocellular carcinoma fulfilling the Milan criteria: an analysis of 293 patients

BACKGROUND: For patients with liver cirrhosis and hepatocellular carcinoma (HCC) satisfying the Milan criteria (single tumor < or =5 cm or 2 or 3 tumors < or =3 cm), orthotopic liver transplantation (OLT) is an effective treatment. Nevertheless, it remains controversial whether OLT is the best treatment strategy for patients with resectable HCC. METHODS: This study included 293 HCC patients (both with and without cirrhosis) oncologically satisfying the Milan criteria who underwent primary and curative liver resection between 1990 and 2003. RESULTS: There were 127 noncirrhotic, 129 Child-Pugh A cirrhotic, and 37 Child-Pugh B cirrhotic patients. Five-year survival rates in each population were 81%, 54%, and 28%, respectively. Coexisting cirrhosis, Child-Pugh classification, alpha-fetoprotein value, tumor burden, and vascular invasion by the tumor were identified as significant prognostic factors. Among these factors, coexisting cirrhosis was the most crucial variable by multivariate analysis. During the initial 3 postoperative years, yearly tumor recurrence rate was 22% in cirrhotic patients and 15% in noncirrhotic patients. In cirrhotic patients, the recurrence rate did not decrease even after three years of tumor-free survival post-resection, whereas in noncirrhotic patients the recurrence rate decreased to 9%. Cirrhosis was associated with a higher probability of recurrence exceeding the Milan criteria. CONCLUSIONS: Hepatic resection offers an acceptable survival result for HCC patients fulfilling the Milan criteria. Coexisting cirrhosis is associated with higher mortality and recurrence rate, possibly due to multicentric carcinogenesis which limits the efficacy of hepatic resection.     

Longterm favorable results of limited hepatic resections for patients with hepatocellular carcinoma: 20 years of experience

BACKGROUND: Recently, anatomic resection has been, in theory, considered preferable for eradicating portal venous tumor extension and intrahepatic metastasis in hepatocellular carcinoma (HCC). We have reported the effectiveness of limited hepatic resection for cirrhotic patients with HCC. STUDY DESIGN: A retrospective study was carried out in 321 patients who underwent curative hepatic resection (anatomic resection, n=201; limited resection, n=120) as the initial treatment for solitary HCC<5 cm in our institution in the period 1985 to 2004 (median followup period 5.1 years). RESULTS: Anatomic resection did not influence overall and recurrence-free survival rates after hepatic resection. In the liver damage A group (n=215), both 5-year overall and recurrence-free survival rates in the anatomic resection group were considerably better than those in the limited resection group (87% versus 76%, p=0.02, and 63% versus 35%, p<0.01, respectively). In the liver damage B group (n=106), both 5-year overall and recurrence-free survival rates in the anatomic resection group were substantially worse than those in the limited resection group (48% versus 72%, p<0.01, and 28% versus 43%, p=0.01, respectively). The results of multivariate analysis revealed that anatomic resection was a notably poor factor in promoting recurrence-free survival in patients with liver damage B. CONCLUSIONS: Anatomic resection should be recommended for noncirrhotic patients (liver damage A) with HCC. Longterm results of limited hepatic resection proved its validity for cirrhotic patients (liver damage B) with HCC.     

Pre-liver transplantation locoregional adjuvant therapy for hepatocellular carcinoma as a strategy to improve longterm survival

BACKGROUND: Preorthotopic liver transplantation locoregional therapy (LRT) for hepatocellular carcinoma (HCC) reduces drop-out rates in patients awaiting orthotopic liver transplantation (OLT). In this study, we investigated the efficacy of LRT as a strategy to improve longterm survival after transplantation. STUDY DESIGN: A retrospective analysis of prospectively collected data identified 100 patients with HCC who underwent OLT between 1985 and 2005. Of these, 46 received LRT in the form of transarterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or a combination of these. RESULTS: The 1-, 3-, and 5-year survivals, regardless of LRT, were 81.3%, 66.1%, and 61.3%, respectively. Demographic data and waiting time for OLT were similar between LRT and untreated groups. Pre-OLT radiologic stage was comparable (LRT: 2.11 +/- 0.74 versus Untreated: 2.39 +/- 0.94; p = 0.16). At the time of transplantation, the LRT group had notable tumor downstaging (1.50 +/- 1.34 versus 2.49 +/- 1.17; p = 0.008). The LRT group had better 5-year survival (82.4% versus 51.8%; p = 0.01), but this improvement was observed in patients with HCC stages II, III, and IV (77.6% versus 37.4%; p = 0.016). Sixteen LRT patients, and none untreated, revealed complete tumor necrosis with no viable tumor cells on explant pathology (pT0). These patients did not experience any longterm recurrence, in contrast to those with similar pre-OLT tumors. CONCLUSIONS: OLT is a viable treatment option for primary HCC. LRT substantially downstages the primary tumor and improves longterm survival in patients with advanced disease. Complete tumor necrosis with LRT is associated with excellent longterm recurrence-free survival.     

Liver Transplantation for Recurrent Hepatocellular Carcinoma on Cirrhosis After Liver Resection: University of Bologna Experience

Liver resection (LR) for patients with small hepatocellular carcinoma (HCC) with preserved liver function, employing liver transplantation (LT) as a salvage procedure (SLT) in the event of HCC recurrence, is a debated strategy.
From 1996 to 2005, we treated 227 cirrhotic patients with HCC transplantable: 80 LRs and 147 LTs of 293 listed for transplantation. Among 80 patients eligible for transplantation who underwent LR, 39 (49%) developed HCC recurrence and 12/39 (31%) of these patients presented HCC recurrence outside Milan criteria. Only 10 of the 39 patients underwent LT, a transplantation rate of 26% of patients with HCC recurrence.
According to intention-to-treat analysis of transplantable HCC patients who underwent LR (n = 80), compared to all those listed for transplantation (n = 293), 5-year overall survival was 66% in the LR group versus 58% in patients listed for LT, respectively (p = NS); 5-year disease-free survival was 41% in the LR group versus 54% in patients listed for LT (p = NS).
Comparable 5-year overall (62% vs. 73%, p = NS) and disease-free (48% vs. 71%, p = NS) survival rates were obtained for SLT and primary LT for HCC, respectively.
LR is a valid treatment for small HCC and in the event of recurrence, SLT is a safe and effective procedure.     

Hepatocellular carcinoma: resection versus transplantation

For decision of adequate surgical therapy and comparison of results differentiation of hepatocellular carcinomas (HCC) in cirrhotic and noncirrhotic livers is important. Liver resection is the treatment of choice for HCC in noncirrhotic liver. Between 4/94 and 8/99 we treated 54 patients with hepatocellular carcinoma (HCC) by subtotal hepatic resection (n = 40) and orthotopic liver transplantation (n = 14). Overall 1- and 3-year survival rates of the resection group were 45 and 25% (median follow up: 3.5 years). One-year survival in the transplantation group was 72% (median follow up: 2.2 years). In patients with HCC in cirrhosis in UICC stage I to III the optimal therapy is a controversial issue. In these patients the results after liver resection are poor due to high operative mortality and recurrence (3-year recurrence-free survival: 30%). Regarding the literature, liver transplantation is the treatment of choice in small (< 3-5 cm, < or = 2 tumors) HCCs arising in cirrhosis with better outcome compared to resection. The data in the literature report 3-year-survival rates after liver transplantation of 60-80%. However, consequent patient selection is necessary for this treatment modality. Due to the limited donor resources liver transplantation is rarely justified in advanced tumors.     

Superiority of transplantation versus resection for the treatment of small hepatocellular carcinoma

The best therapy for hepatocellular carcinoma (HCC) is still debated. Hepatic resection (HR) is the treatment of choice for single HCC in Child A patients, whereas liver transplantation (OLT) is usually reserved for Child B and C patients with multiple nodules. The aim of this study was to compare HR and OLT for HCC within the Milan criteria on an intention-to-treat basis. Forty-eight patients were treated by OLT and 38 by HR. Three- and 5-year patient survival rates were significantly higher (P = .0057) in the OLT group (79% and 74%) than after HR (61% and 26%). The 3- and 5-year disease-free survival rate was better (P = .0005) for OLT (74% and 74%) versus HR (41% and 11%). The probability of HCC recurrences after resection was greater (P = .0002) than after transplantation, achieving 31% and 76% for HR and 2% and 2% for OLT at 3 and 5 years after surgery. The median waiting list time was 118 days; two patients dropped out for HCC progression. We concluded that OLT is superior to HR for small HCC in cirrhotic patients assuming that OLT can be performed within 6 to 10 months after listing to reduce dropouts due to tumor progression.     

The Impact of Pre-Operative Loco-Regional Therapy on Outcome After Liver Transplantation for Hepatocellular Carcinoma

No prior studies have shown that pre-operative loco-regional therapy for hepatocellular carcinoma (HCC) improves survival following orthotopic liver transplantation (OLT). We performed subgroup analyses according to pathologic HCC stage among 168 patients who underwent OLT to test the hypothesis that pre-operative loco-regional therapy confers a survival advantage in a subgroup at intermediate risk for HCC recurrence. Patients with pathologic T3 HCC meeting the proposed UCSF expanded criteria (single lesion not exceeding 6.5 cm or two to three lesions none > 4.5 cm with total tumor diameter within 8 cm) had a similar 5-year recurrence-free survival as patients with pathologic T2 HCC (88.5% vs. 93.8%; p = 0.56). In the subgroup with pathologic T2 or T3 HCC, the 5-year recurrence-free survival was 93.8% for the 85 patients who received pre-operative loco-regional therapy, versus 80.6% for the other 41 patients without treatment (p = 0.049). The treatment benefit, according to 5-year recurrence-free survival, appeared greater for pathologic T3 (85.9% vs. 51.4%; p = 0.05) than T2 HCC (96.4% versus 87.1%; p = 0.12). In conclusion, although the lack of a randomized controlled design precludes drawing firm conclusions, our results suggest that pre-operative loco-regional therapy may confer a survival benefit after OLT in the subgroup with pathologic T2 and T3 HCC.     

Impact of Tumor Characteristic on the Outcome of Liver Transplantation in Patients With Hepatocellular Carcinoma

Introduction

Orthotopic liver transplantation (OLT) is a well-established treatment for cirrhotic patients with hepatocellular carcinoma (HCC) who meet the Milan criteria. The aim of this study was to identify predictors of survival among 65 patients with HCC in cirrhotic livers who underwent liver transplantation (OLT).

Methods

From January 2001 to December 2008, we performed 655 OLT in 615 patients. HCC was diagnosed in 58 patients before OLT and in 65 by histological examination of the explanted livers; 74% of the patients met Milan criteria by histological examination.

Results

The median follow-up was 27 months (range = 1-96). We analyzed patient age and gender, etiology of liver disease, Child score at transplantation, rejection episodes, tumor number/size, vascular invasion, and differentiation grade. There was no significant difference in survival among patients grouped according to the Model for End-stage Liver Disease staging system for HCC. The 5-year survival of patients with low differentiated (G3) HCC was significantly worse than that of those with moderately differentiated (G2) or well-differentiated (G1) HCC: 50%, 81%, and 86% respectively, (P < .01). Patients with microvascular invasion displayed a worse 5-year survival than those without vascular invasion (42% vs 80%; P < .01).

Conclusions

The analysis indicated that the histological grade of the tumors and evidences of microscopic vascular invasion were the most useful predictive factors for overall survival among patients with cirrhosis after liver transplantation for HCC.     

Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation

OBJECTIVE: To evaluate the survival results and pattern of recurrence after resection of potentially transplantable small hepatocellular carcinomas (HCC) in patients with preserved liver function, with special reference to the implications for a strategy of salvage transplantation. SUMMARY BACKGROUND DATA: Primary resection followed by transplantation for recurrence or deterioration of liver function has been recently suggested as a rational strategy for patients with HCC 5 cm or smaller and preserved liver function. However, there are no published data on transplantability after HCC recurrence or long-term deterioration of liver function after resection of small HCC in Child-Pugh class A patients. Such data are critical in determining the feasibility of salvage transplantation. METHODS: From a prospective database of 473 patients with resection of HCC between 1989 and 1999, 135 patients age 65 years or younger had Child-Pugh class A chronic liver disease (chronic hepatitis or cirrhosis) and transplantable small HCC (solitary < or =5 cm or two or three tumors < or = 3 cm). Survival results were analyzed and the pattern of recurrence was examined for eligibility for salvage transplantation based on the same criteria as those of primary transplantation for HCC. RESULTS: Overall survival rates at 1, 3, 5, and 10 years were 90%, 76%, 70%, and 35%, respectively, and the corresponding disease-free survival rates were 74%, 50%, 36%, and 22%. Cirrhosis and oligonodular tumors were predictive of worse disease-free survival. Patients with concomitant oligonodular tumors and cirrhosis had a 5-year overall survival rate of 48% and a disease-free survival rate of 0%, which were significantly worse compared with other subgroups. At a median follow-up of 48 months, 67 patients had recurrence and 53 (79%) of them were considered eligible for salvage transplantation. Decompensation from Child-Pugh class A to B or C without recurrence occurred in only six patients. CONCLUSIONS: For Child-Pugh class A patients with small HCC, hepatic resection is a reasonable first-line treatment associated with a favorable 5-year overall survival rate. A considerable proportion of patients may survive without recurrence for 5 or even 10 years; among those with recurrence, the majority may be eligible for salvage transplantation. These data suggest that primary resection and salvage transplantation may be a feasible and rational strategy for patients with small HCC and preserved liver function. Primary transplantation may be a preferable option for the subset of patients with oligonodular tumors in cirrhotic liver in view of the poor survival results after resection.     

Transarterial chemoembolization before liver transplantation in 60 patients with hepatocellular carcinoma

Tumor recurrence is a major problem after orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC). In 60 patients OLT was performed for HCC after pretreatment by repeated transarterial chemoembolization (TACE). Forty-four recipients exceeded the Milan criteria. Recurrence-free 5-year survival was 65.2% and 5-year freedom from recurrence was 73.2%. During the waiting time, 14 patients experienced minimal change, which did not fulfill the definition of tumor progression according to official oncological criteria. Five-year freedom from recurrence among patients with stable compared with progressive disease was 93.3% versus 28.1%, respectively (P = .0001). A strict TACE pretreatment protocol may select patients with obviously biologically less aggressive tumors, who are suitable for OLT even if the HCC exceeds the commonly accepted listing criteria.     

Liver resection as a bridge to transplantation for hepatocellular carcinoma on cirrhosis: a reasonable strategy?

OBJECTIVE: To assess the viability of a strategy of primary resection with secondary liver transplantation (LT) for hepatocellular carcinoma (HCC) on cirrhosis. SUMMARY BACKGROUND DATA: LT is the optimal treatment of HCC with cirrhosis. Owing to organ shortage, liver resection is considered as a reasonable first-line treatment of patients with small HCC and good liver function, with secondary LT as a perspective in case of recurrence. The viability of such strategy, positively explored in theoretical models, is not documented in clinical practice. METHODS: Among 358 consecutive patients with HCC on cirrhosis treated by liver resection (n = 163; 98 of whom were transplantable) or transplantation (n = 195), the feasibility and outcome of secondary transplantation was evaluated in a 2-step fashion. First, secondary LT for tumor recurrence after resection (n = 17) was compared with primary LT (n = 195), to assess the risk and the outcome of secondary LT in patients who effectively succeeded to be treated by this approach. Second, primary resection in transplantable patients (n = 98) was compared with that of primary LT (n = 195) on an intention-to-treat basis, to assess the outcome of each treatment strategy and to determine the proportion of resected patients likely to be switched for secondary LT. Transplantability of resected patients was retrospectively determined according to selection criteria of LT for HCC. RESULTS: Operative mortality (< or =2 months) of secondary LT was significantly higher than that of primary LT (28.6% versus 2.1%; P = 0.0008) as was intraoperative bleeding (mean transfused blood units, 20.7 versus 10.5; P = 0.0001). Tumor recurrence occurred more frequently after secondary than after primary LT (54% versus 18%; P = 0.001). Posttransplant 5-year overall survival was 41% versus 61% (P = 0.03), and disease-free survival was 29% versus 58% (P = 0.003) for secondary and primary LT, respectively.Of 98 patients treated by resection while initially eligible for transplantation, only 20 (20%) were secondarily transplanted, 17 of whom (17%) for tumor recurrence and 3 (3%) for hepatic decompensation. Transplantability of tumoral recurrence was 25% (17 of 69 recurrences). Compared with primarily transplanted patients, transplantable resected patients had a decreased 5-year overall survival (50% versus 61%; P = 0.05) and disease-free survival (18% versus 58%; P < 0.0001), despite the use of secondary LT.On a multivariate analysis including 271 patients eligible for transplantation and treated by either liver resection or primary LT, liver resection alone (P < 0.0001; risk ratio [RR] = 3.27) or liver resection with secondary LT (P < 0.05; RR= 1.87) emerged as negative independent factors of disease-free survival as compared with primary LT. A number of nodules > 3 (P = 0.002; RR= 2.02) and a maximum tumor size exceeding 30 mm (P < 0.0001; RR=1.93) were also predictive of lower disease-free survival. CONCLUSIONS: LT after liver resection is associated with a higher operative mortality, an increased risk of recurrence, and a poorer outcome than primary LT. In addition, liver resection as a bridge to LT impairs the patient transplantability and the chance of long-term survival of cirrhotic patients with HCC. Primary LT should therefore remain the ideal choice of treatment of a cirrhotic patient with HCC, even when the tumor is resectable.     

Liver transplantation criteria for hepatocellular carcinoma should be expanded: a 22-year experience with 467 patients at UCLA

OBJECTIVE: To assess the efficacy of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) and the impact of current staging criteria on long term survival. SUMMARY BACKGROUND DATA: HCC is becoming an increasingly common indication for OLT. Medicare approves OLT only for HCCs meeting the Milan criteria, thus limiting OLT for an expanding pool of potential liver recipients. We analyzed our experience with OLT for HCC to determine if expansion of criteria for OLT for HCC is warranted. METHODS:: All patients undergoing OLT for HCC from 1984 to 2006 were evaluated. Outcomes were compared for patients who met Milan criteria (single tumor < opr =5 cm, maximum of 3 total tumors with none >3 cm), University of California, San Francisco (UCSF) criteria (single tumor <6.5 cm, maximum of 3 total tumors with none >4.5 cm, and cumulative tumor size <8 cm), or exceeded UCSF criteria. RESULTS: A total of 467 transplants were performed for HCC. At mean follow up of 6.6 +/- 0.9 years, recurrence rate was 21.2%, and overall 1, 3, and 5-year survival was 82%, 65%, and 52%, respectively. Patients meeting Milan criteria had similar 5-year post-transplant survival to patients meeting UCSF criteria by preoperative imaging (79% vs. 64%; P = 0.061) and explant pathology (86% vs. 71%; P = 0.057). Survival for patients with tumors beyond UCSF criteria was significantly lower and was below 50% at 5 years. Multivariate analysis showed that tumor number (P < 0.001), lymphovascular invasion (P < 0.001), and poor differentiation (P = 0.002) independently predicted poor survival. CONCLUSIONS: This largest single institution experience with OLT for HCC demonstrates prolonged survival after liver transplantation for tumors beyond Milan criteria but within UCSF criteria, both when classified by preoperative imaging and by explant pathology. Measured expansion of OLT criteria is justified for tumors not exceeding the UCSF criteria.     

Liver transplantation for hilar cholangiocarcinoma: Spanish experience

INTRODUCTION: Palliative treatment for nondisseminated irresectable hilar cholangiocarcinoma (HCC) carries a 0% 5-year survival rate. The role of orthotopic liver transplantation (OLT) in these patients is controversial because the survival rate is lower than that for other indications for transplantation and the lack of available donor organs. The aim of this paper was to review the Spanish experience in OLT for HCC and identify prognostic factors for survival. METHODS: We retrospectively reviewed 36 patients undergoing OLT for HCC over 13 years. RESULTS: The actuarial survival rate at 1, 3, and 5 years was 82%, 53%, and 30%, respectively. The main cause of death was tumor recurrence (53%). In the univariate analysis, the factors for a poor prognosis were vascular invasion (P<.001) namely 0% survival at 3 years when present versus 63% and 35% at 3 and 5 years, respectively, when it was not; and stages III to IVA (P<.05), namely 15% survival at 5 years versus 47% for stages I to II. Lymph node and perineural invasion also reduce survival. In the multivariate analysis, the factors for poor prognosis included vascular invasion (P<.01) and stages III to IVA (P<.01). CONCLUSION: OLT for nondisseminated irresectable HCC has higher survival rates at 3 and 5 years than palliative treatments, especially with initial stage tumors, which means that more information is needed to better select cholangiocarcinoma patients for transplantation.     

Selection criteria for hepatic resection in patients with large hepatocellular carcinoma larger than 10 cm in diameter

BACKGROUND: The role of hepatic resection for large hepatocellular carcinoma (HCC) larger than 10 cm remains unclear. STUDY DESIGN: Perioperative and longterm outcomes of 120 patients with HCC larger than 10 cm who underwent resection (group A) were compared with 368 patients with smaller HCC (group B). The prognostic factors in group A were analyzed. RESULTS: A higher proportion of patients underwent major hepatic resection in group A than in group B (90% versus 57.6%, p = 0.001), but the hospital mortality was similar (5.0% versus 4.6%, p = 0.874). Group A had worse longterm overall survival (median 18.8 months versus 62.8 months, p < 0.001) and disease-free survival (median 5.5 months versus 25.4 months, p < 0.001) than group B. Macroscopic residual tumor, macroscopic venous invasion, and multiple tumors were identified as independent prognostic factors in group A. The median survival of patients with residual tumor and those with curative resection was 7.7 months and 20.8 months, respectively. The median survival of patients with curative resection of solitary HCC larger than 10cm without macroscopic venous invasion was 38.0 months; that of patients with both macroscopic venous invasion and multiple tumors was only 10.5 months. CONCLUSIONS: Hepatic resection is a safe and effective treatment for HCC larger than 10cm when liver function reserve is satisfactory and when curative resection can be expected. Patients with solitary HCC larger than 10cm without macroscopic venous invasion can enjoy longterm survival after surgery, and we propose hepatic resection as a standard treatment for this group of patients.     

Predictors of survival after liver transplantation for hepatocellular carcinoma associated with Hepatitis C.

The efficacy of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) is not well defined. This study examines the variables that may determine the outcome of OLT for HCC in HCV patients. From 1990 to 1999, 463 OLTs were performed for HCV cirrhosis. Of these patients, 67 with concurrent HCC were included in the study. Univariate and multivariate analyses considered the following variables: gender, pTNM stage, tumor size, number of nodules, vascular invasion, incidental tumors, adjuvant chemotherapy, preoperative chemoembolization, alpha-fetoprotein (AFP) tumor marker, lobar distribution, and histological grade. Overall OLT survival of HCV patients diagnosed with concomitant HCC was significantly lower when compared to patients who underwent OLT for HCV alone at 1, 3, and 5 years (75%, 71%, and 55% versus 84%, 76%, and 75%, respectively; P < 0.01). Overall survival of patients with stage I HCC was significantly better than patients with stage II, III, or IV (P < .05). Eleven of 67 patients developed tumor recurrence. Sites of recurrence included transplanted liver (5), lung (5), and bone (1). Twenty-four of 67 patients (36%) died during the follow-up time. Causes of deaths included recurrent HCC in 8 of 24 patients (12%) and recurrent HCV in 3 of 24 patients (4.5%), whereas 13 (19.5%) patients died from causes that were unrelated to HCV or HCC. Both univariate and multivariate analysis demonstrated that pTNM status (I versus II, III, and IV; P < .05) was a reliable prognostic indicator for patient survival. Presence of vascular invasion (P = .0001) and advanced pTNM staging (P = .038) increased risk of recurrence. Multivariate analysis showed that pretransplant chemoembolization and adjuvant chemotherapy reduced risk of death after OLT in HCC recipients. In conclusion, this study demonstrates the effectiveness of OLT for patients with HCC in a large cohort of chronic HCV patients. Advanced tumor stage, and particularly vascular invasion, are poor prognostic indicators for tumor recurrence. Early pTNM stage, adjuvant chemotherapy, and preoperative chemoembolization were associated with positive outcomes for patients who underwent OLT for concomitant HCV and HCC.     

Adjuvant chemotherapy improves survival after liver transplantation for hepatocellular carcinoma.

OBJECTIVE: The aim of this study was to evaluate the effect of postoperative adjuvant chemotherapy on the recurrence rate and survival of patients after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Historically, liver transplantation for HCC has yielded poor long-term survival. Multimodality therapy has been initiated in an effort to improve survival statistics. METHODS: Twenty-five patients were placed on 6 months of intravenous fluorouracil, doxorubicin, and cisplatin after OLT. Risk factors, recurrence rates, and survival rates were analyzed and compared with historic controls. RESULTS: Overall long-term survival in the protocol patients was 46% at 3 years, improved over our historic controls of 5.8% at 3 years (p = 0.0001). Overall recurrence rate was 20% (n = 4). Possible risk factors, such as tumor size, vascular invasion, multifocality, capsular invasion, and tumor differentiation, were not found to be significantly predictive of survival. Three patients with long-term, disease-free survival had tumors > 5 cm. Side effects from chemotherapy were common, but rarely severe. CONCLUSIONS: This study suggests that adjuvant chemotherapy after transplantation for HCC can provide long-term cure and may improve survival, even in patients with stage III and IV disease.     

Intrahepatic cholangiocarcinoma: resectability, recurrence pattern, and outcomes

Intrahepatic cholangiocarcinoma (IHC) is a rare primary hepatic tumor of bile duct origin for which resection is the most effective treatment. But resectability, outcomes after resection, and recurrence patterns have not been well described. Patients with IHC were identified from a prospective database. Demographic data, tumor characteristics, and outcomes were analyzed. From March 1992 to September 2000, 53 patients with hepatic tumors underwent exploration and were found to have pure IHC on pathologic analysis. Patients with mixed hepatocellular and cholangiocarcinoma tumors were excluded. At exploration, 20 patients were unresectable for an overall resectability rate of 62% (33 of 53). Median survival for patients submitted to resection was 37.4 months versus 11.6 months for patients undergoing biopsy only (p = 0.006; median followup for surviving patients, 15.6 months). Actuarial 3-year survival was 55% versus 21%, respectively. Factors predictive of poor survival after resection included vascular invasion (p = 0.0007), histologically positive margin (p = 0.009), or multiple tumors (p = 0.003). After resection, 20 of 33 patients (61%) recurred at a median of 12.4 months. Sites of recurrence included the liver (14), retroperitoneal or hilar nodes (4), lung (4), and bone (2). The median disease-free survival was 19.4 months, with a 3-year disease-free survival rate of 22%. Factors predictive of recurrence were multiple tumors (p = 0.0002), tumor size (p = 0.001), and vascular invasion (p = 0.01). About two-thirds of patients who appeared resectable on preoperative imaging were amenable to curative resection at the time of operation. Although complete resection improved survival, recurrence was common. The majority of recurrences were local or regional, which may help guide future adjuvant therapy strategies.     

Hepatectomy as Treatment of Choice for Hepatocellular Carcinoma in Elderly Cirrhotic Patients

In recent decades liver resection has become a safe procedure; however, the outcome of hepatectomies in aged cirrhotic patients is often uncertain. To elucidate early and long-term outcomes of hepatectomy for HCC in the elderly, we studied 241 cirrhotic patients who underwent liver resection for HCC between 1985 and 2003. According to their age at the time of surgery, patients were divided into two groups: aged > 70 years (64 patients) and aged ≤ 70 years (177 patients). Operative mortality was 3.1% in the elderly and 9.6% in the younger group (p = 0.113). Postoperative morbidity and liver failure rates were higher in the younger group (42.4% versus 23.4%, p = 0.0073; 12.9% versus l.6%, p = 0.0065). Five-year survival rates are 48.6% in the elderly group and 32.3% in the younger group (p = 0.081). Considering only radical resections in Child-Pugh A patients, survival remains similar in the two groups (p = 0.072). Disease-free survival is not different in the two groups. A survival analysis performed according to the tumor diameter shows a better survival for elderly Child-Pugh A patients with HCC larger than 5 cm radically resected (50.8% versus 16.1% 5-year survival, p = 0.034). In univariate analysis, tumor size is not a prognostic factor in the elderly, whereas younger patients with large tumors have a worse outcome. Age by itself is not a contraindication for surgery, and selected cirrhotic patients with HCC who are 70 years of age or older could benefit from resection, even in the presence of large tumors. Long-term results of liver resections for HCC in the elderly may be even better than in younger patients.     

肝移植治疗原发性肝癌60例

目的　评价肝移植治疗原发性肝癌的疗效和受体选择。方法　对 1993年 9月～ 2 0 0 2年 9月施行的 6 0例次肝癌肝移植患者的临床资料进行回顾性分析 ,比较不同时期肝癌肝移植的疗效和大、小肝癌的术后存活率。结果　 1993年 9月～ 2 0 0 0年 7月共实施肝癌肝移植 2 3例 ,1个月、1年、2年、3年存活率分别为 73 9%、6 0 9%、4 3 5 %和 2 9 0 %。 2 0 0 0年 8月～ 2 0 0 2年 9月共实施肝癌肝移植 37例 ,1个月、1年、2年存活率分别为 89 2 %、75 8%和 6 1 2 %。术前肝功能ClildA或B级受体的 1月存活率为 89 5 % ,较ClildC级的 72 7%差异有显著性意义 (P <0 0 5 )。大肝癌 4 1例 ,半数存活期为 18 0个月 ,1个月、1年、2年、3年存活率分别为 82 9%、6 3 1%、4 6 7%和 37 4 %。小肝癌 19例 ,存活期平均为 2 9 6个月 ,1个月、1年、2年、3年存活率分别为 84 2 %、76 6 %、6 5 6 %和6 5 6 % ,大、小肝癌累积存活率差异无显著意义。大、小肝癌的复发率分别为 2 7 7%和 15 8% ,获得长期存活的患者大部分生活质量良好。结论　肝移植是治疗原发性肝癌合并肝硬化的有效方法 ,对于明确合并有肝硬化门脉高压的小肝癌应提倡及时进行肝移植治疗 ,适当选择部分大肝癌作为移植受体仍有一定的合理性 ,血管侵犯或肝外     

Multifocal manifestation does not affect vascular invasion of hepatocellular carcinoma: implications for patient selection in liver transplantation

BACKGROUND AND AIMS: Liver transplantation (OLT) for hepatocellular carcinoma (HCC) improves patient survival when tumor size and number are limited according to the Milan criteria. However, the impact of tumor size vs. the number of lesions for tumor recurrence after OLT is unclear. Microvascular invasion appears to be a significant risk factor for tumor recurrence. Therefore, it was the aim of this study to investigate tumor differentiation and microvascular invasion in relation to tumor number and size and their impact on survival after transplantation. PATIENTS AND METHODS: In 97 adult HCC patients who underwent OLT between June 1985 and December 2005 the incidence of microvascular invasion, tumor differentiation, and the number and size of tumor lesions were analyzed retrospectively. Their impact on survival was studied by multivariate analysis. RESULTS: Microvascular invasion was the only independent negative predictor of survival after OLT for HCC (p = 0.025). Tumor size > 5 cm was predictive for microvascular invasion (p = 0.007). In contrast, tumor number did not affect the incidence of microvascular invasion or cumulative survival. CONCLUSION: The size of the largest HCC lesion, but not the number of tumors, determined microvascular invasion, a predictor of the outcome following OLT for HCC. Thus, the number of HCC lesions should not be applied to patient selection prior to OLT. These data support the extension of the Milan criteria for the selection of HCC patients for OLT with regard to tumor number, but not tumor size.