Beyond the Milan criteria: what risks for patients with hepatocellular carcinoma progression before liver transplantation?

BACKGROUND: To date the selection of the best candidates for liver transplantation (LT) owing to hepatocellular carcinoma (HCC) has been mainly based on tumor morphological characteristics (nodule diameter and number), which have resulted to be independent risk factors for short long-term survival and a high rate of tumor recurrence. METHODS: The study cohort included 118 patients among the 166 with HCC transplanted at our unit from January 2000 to December 2007. Patients were classified according to response to locoregional treatments before LT: progressive Group A; complete Group B; partial Group C; stable Group D. RESULTS: The 3-year and 5-year overall survival rates were 65.5% and 48.9% for Group A versus 84.8% and 74.6% for Group BCD (P = 0.01). The 3-year and 5-year disease-free survival rates were 74% and 74% for Group A and 95.7% and 93% for Group BCD (P = 0.007). HCC progression was the only independent risk factor according to Cox regression P = 0.014--odds ratio 4.4 (1.35-14.3). CONCLUSION: After aggressive HCC treatment before LT, imaging progression while on the waiting list was a strong predictor of high HCC recurrence rate also in patients who met the Milan criteria. Lack of imaging progression can contribute toward the selection of good transplant candidates for HCC together with the Milan criteria.

Living donor liver transplantation for hepatocellular carcinoma: the impact of neo-adjuvant treatments on the long term results.

BACKGROUND/AIMS: LDLT may represent a valid therapeutic option allowing several advantages for patients affected by HCC and waiting for liver transplantation (LT). However, some reports show a worse long term survival and disease free survival among patients treated by LDLT for HCC than deceased donor liver transplantation (DDLT) recipients. METHODOLOGY: Among 1145 LT patients, 63 received LDLT. From January 2000 to December 2008, 179 patients underwent LT due to HCC, 30 (16.7%) received LDLT and 154 (86.0%) received DDLT. Patients were selected based on the Milan criteria. TACE, radiofrequency ablation, percutaneous alcoholization, or liver resection were applied as downstaging procedures, while on the waiting list. RESULTS: Overall 3- and 5-year survival rate was 77.3% and 68.7% vs. 82.8% and 76.7%, respectively for LDLT and DDLT recipient with not significant differences. Moreover, 3- and 5- years of recurrence free survival rate was 95.5% (LDLT) vs. 90.5% and 89.4% (DDLT) and resulted not significantly different. CONCLUSIONS: LDLT guarantees same long term results than DDLT if the selection criteria of candidates are analogues. Milan criteria remains a valid candidate selection tool to obtain optimal long term results in LDLT. An aggressive downstaging policy seems to improve the long-term results in LDLT, thus LRT may be considered useful to prevent tumor progression waiting for transplantation as well as a neoadjuvant therapy for HCC. A literature detailed meta-analysis could definitely clarify if LDLT is an independent risk factor for HCC recurrence.

Surgical treatment of hepatocellular cancer in the era of hepatic transplantation.

BACKGROUND: This study compares liver resection (LR) or transplantation (LTx) in an attempt to reevaluate the indications for treatment. STUDY DESIGN: One hundred fifty-four LRs and 121 LTxs performed from 1985 to 1999 were considered. Survival and recurrence rate, together with age, gender, liver disease, Child-Pugh classification, alpha-fetoprotein (AFP), tumor capsule, vascular invasion, size, number of nodules, histologic grade, and pTNM were considered. Followup was completed in all cases (mean +/- SD = 3.2 +/- 2.9 years). RESULTS: The 5- and 10-year actuarial survival rates were 61.7% and 59.8% in LTx and 46.9% and 28.0% in LR (p = 0.08). Recurrence-free survival was 85.9% and 85.9%, respectively, in LTx and 42.8% and 30.7% in LR (p < 0.0001). In both groups, size, capsule, AFP, vascular invasion, grade, pTNM, Child-Pugh classification, and age were all significantly related to survival and cancer recurrence. pTNM, AFP, Child-Pugh classification, and age, in LR, and capsule, AFP, and viral cirrhosis, in LTx, were significant independent variables in Cox's regression model for survival. Only AFP, vascular invasion, and grade were significant in both groups for recurrence. CONCLUSIONS: LTx offers better recurrence freedom than LR, but longterm survival is not significantly different in the two series. A strict selection should be made to optimize graft allocation. Size and multifocality should not be considered absolute contraindications for LTx. AFP, vascular invasion, and grade are more likely to reflect the risk of recurrence of the disease. LR should be considered in patients who do not fulfill transplant criteria and also in some categories of patients with certain tumor characteristics (small resectable tumors in well-compensated cirrhosis).

Percutaneous Transhepatic Bile Duct Ablation with n-Butyl Cyanoacrylate in the Treatment of a Biliary Complication after Split Liver Transplantation.

Biliary complications continue to be a major cause of morbidity after split-liver transplantation (SLT). In this report we describe an uncommon late biliary complication. One year after SLT the patient showed an intrahepatic bile dicy dilatation with severe cholangitis episodes. The segmentary bile duct of hepatic segment VI-VII draining in the left duct was unidentified and tied at the time of the in situ split-liver procedure. We perform a permanent obliteration of the dilated intrahepatic ducts by a percutaneous embolization using an n-butyl cyanoacrylate (NABC). The management of biliary complications after SLT requires a multidisciplinary approach. The use of NBCA in obliteration of a dilated bile duct seems to be a safe procedure with good results providing a less invasive option than hepatic resection and decreasing the morbidity associated with chronic external biliary drainage. Further studies are needed to determine whether this approach is effective and safe and whether it could reduce hospital stay and cost.

Liver transplantation for hepatocellular cancer: should the current indication criteria be changed?

Liver transplantation (LTx) is the best treatment for hepatocellular carcinoma (HCC), but should be offered only to selected patients. The usual procedure is to transplant only for small and unilobular tumors. The aim of this paper is to verify whether the actual indication criteria are still justified. The details of 121 patients with HCC who were submitted to LTx from 1985 to 2000 were analyzed. Age, gender, liver disease, Child class, alpha-fetoprotein (AFP) level, presence of tumor capsule, vascular invasion, size and number of nodules, histological grade, and pTNM were considered. The 5- and 10-year actuarial survival rates were 61.7% and 53.1%. Freedom from recurrence was 85.9% and 85.9%, respectively. At univariate analysis, size, presence of capsule, AFP levels, vascular invasion, grade, pTNM, transarterial chemoembolization (TACE), Child class, and age were all significantly related to survival and/or cancer recurrence. Presence of capsule, AFP levels, and viral cirrhosis were independent variables in Cox's analysis for survival, whereas histological grade, AFP levels, and vascular invasion were significant independent variables for recurrence. In conclusion, a strict selection should be made to optimize graft allocation while size and multifocality should probably no longer be considered a contraindication for LTx. Histological grade, AFP levels, and vascular invasion, as indicator of tumor behavior, more likely reflect the risk of recurrence.