Risk factors of hepatocellular carcinoma recurrence after liver transplantation: accuracy of the alpha-fetoprotein model in a single-center experience.

BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) and cirrhosis after a liver transplantation (LT) is a major concern, and a strict Milan criteria selection of candidates does not accurately discriminate the relapse rate after LT. PURPOSE: This study sought to analyze the risk factors affecting tumor recurrence after LT for related cirrhosis HCC and the application of the French prognostic model (preLT alpha-fetoprotein [AFP], size, number) in a single center. METHODS: In a retrospective observational study of LT for HCC and cirrhosis, clinicopathological features were analyzed. Also, the preoperative and postoperative AFP model score was calculated with a cutoff of 2. RESULTS: Of 480, 109 patients underwent cadaveric LT for HCC. Eight of them had a relapse (7%). High AFP level, AFP model score >2, high pathological tumor-node-metastasis (pTNM) stage, poor differentiation, macrovascular-microvascular invasion, infiltration, and R1 margin were statistically significant (P < .05) for recurrence. Also, in the preoperative model, AFP score >2 was a predictor of worse survival (1-, 3-, 5-, 10-year survival of 81%, 51%, 30%, 30% vs 90%, 76%, 73%, 69% in ≤2, with P = .005). Regarding the postoperative model, similar results were found (1-, 3-, 5-, 10-year survival of 84%, 47%, 37%, 37% vs 90%, 78%, 73%, 52%, P = .028) between AFP model score >2 and ≤2, respectively. However, Milan and up-to-7 criteria were not accurate in recurrence nor in survival. CONCLUSIONS: The French AFP model has proven to be a more discerning prognostic tool than other established criteria in the prediction of recurrence and survival. Also, in postoperative prognosis, pathological risk factors for relapse such as pTNM, differentiation grade, macrovascular-microvascular invasion, infiltration, and R1 margin have been predictors of recurrence.

"Very early" intrahepatic cholangiocarcinoma in cirrhotic patients: should liver transplantation be reconsidered in these patients?

A retrospective cohort multicenter study was conducted to analyze the risk factors for tumor recurrence after liver transplantation (LT) in cirrhotic patients found to have an intrahepatic cholangiocarcinoma (iCCA) on pathology examination. We also aimed to ascertain whether there existed a subgroup of patients with single tumors ≤2 cm ("very early") in which results after LT can be acceptable. Twenty-nine patients comprised the study group, eight of whom had a "very early" iCCA (four of them incidentals). The risk of tumor recurrence was significantly associated with larger tumor size as well as larger tumor volume, microscopic vascular invasion and poor degree of differentiation. None of the patients in the "very early" iCCA subgroup presented tumor recurrence compared to 36.4% of those with single tumors >2 cm or multinodular tumors, p = 0.02. The 1-, 3- and 5-year actuarial survival of those in the "very early" iCCA subgroup was 100%, 73% and 73%, respectively. The present is the first multicenter attempt to ascertain the risk factors for tumor recurrence in cirrhotic patients found to have an iCCA on pathology examination. Cirrhotic patients with iCCA ≤2 cm achieved excellent 5-year survival, and validation of these findings by other groups may change the current exclusion of such patients from transplant programs.

Intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma in patients undergoing liver transplantation: a Spanish matched cohort multicenter study.

OBJECTIVE: To evaluate the outcome of patients with hepatocellular-cholangiocarcinoma (HCC-CC) or intrahepatic cholangiocarcinoma (I-CC) on pathological examination after liver transplantation for HCC. BACKGROUND: Information on the outcome of cirrhotic patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study is limited. METHODS: Multicenter, retrospective, matched cohort 1:2 study. STUDY GROUP: 42 patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study; and control group: 84 patients with a diagnosis of HCC. I-CC subgroup: 27 patients compared with 54 controls; HCC-CC subgroup: 15 patients compared with 30 controls. Patients were also divided according to the preoperative tumor size and number: uninodular tumors 2 cm or smaller and multinodular or uninodular tumors 2 cm or larger. Median follow-up: 51 (range, 3-142) months. RESULTS: The 1-, 3-, and 5-year actuarial survival rate differed between the study and control groups (83%, 70%, and 60% vs 99%, 94%, and 89%, respectively; P < 0.001). Differences were found in 1-, 3-, and 5-year actuarial survival rates between the I-CC subgroup and their controls (78%, 66%, and 51% vs 100%, 98%, and 93%; P < 0.001), but no differences were observed between the HCC-CC subgroup and their controls (93%, 78%, and 78% vs 97%, 86%, and 86%; P = 0.9). Patients with uninodular tumors 2 cm or smaller in the study and control groups had similar 1-, 3-, and 5-year survival rate (92%, 83%, 62% vs 100%, 80%, 80%; P = 0.4). In contrast, patients in the study group with multinodular or uninodular tumors larger than 2 cm had worse 1-, 3-, and 5-year survival rates than their controls (80%, 66%, and 61% vs 99%, 96%, and 90%; P < 0.001). CONCLUSIONS: Patients with HCC-CC have similar survival to patients undergoing a transplant for HCC. Preoperative diagnosis of HCC-CC should not prompt the exclusion of these patients from transplant option.

Statistical quality control charts for liver transplant process indicators: evaluation of a single-center experience.

Liver transplantation, the best option for many end-stage liver diseases, is indicated in more candidates than the donor availability. In this situation, this demanding treatment must achieve excellence, accessibility and patient satisfaction to be ethical, scientific, and efficient. The current consensus of quality measurements promoted by the Sociedad Española de Trasplante Hepático (SETH) seeks to depict criteria, indicators, and standards for liver transplantation in Spain. According to this recommendation, the Canary Islands liver program has studied its experience. We separated the 411 cadaveric transplants performed in the last 15 years into 2 groups: The first 100 and the other 311. The 8 criteria of SETH 2010 were correctly fulfilled. In most indicators, the outcomes were favorable, with an actuarial survivals at 1, 3, 5, and 10 years of 84%, 79%, 76%, and 65%, respectively; excellent results in retransplant rates (early 0.56% and long-term 5.9%), primary nonfunction rate (0.43%), waiting list mortality (13.34%), and patient satisfaction (91.5%). On the other hand, some indicators of mortality were worse as perioperative, postoperative, and early mortality with normal graft function and reoperation rate. After the analyses of the series with statistical quality control charts, we observed an improvement in all indicators, even in the apparently worst, early mortality with normal graft functions in a stable program. Such results helped us to discover specific areas to improve the program. The application of the quality measurement, as SETH consensus recommends, has shown in our study that despite being a consuming time process, it is a useful tool.

Hepatocellular carcinoma and liver transplantation: a 12-year experience.

BACKGROUND: Orthotopic liver transplantation (OLT) for patients with cirrhosis and concomitant hepatocellular carcinoma (HCC) in early stages is the treatment of choice, with an acceptable recurrence rate and excellent survival. AIM: We sought to evaluate (1) the accuracy of preoperative imaging; (2) the impact of pre-OLT treatments on survival and recurrence; and (3) the influence of beyond Milan criteria selection on global outcomes. METHODS: We studied a cohort of 65 patients with HCC among 300 consecutive OLTs over a single 12-year experience. We analyzed the overall outcomes of survival and recurrence, the accuracy of preoperative diagnosis and staging the influence of neoadjuvant treatment prior to OLT, and the effect on overall outcomes beyond the Milan criteria in our series. RESULTS: The 65 transplants were performed for HCC, mostly in association with hepatitis C virus and alcoholic cirrhosis with HTP. At a mean follow-up of 40.32 months, the recurrence rate was 5.7% among the 61 HCC confirmed by histopathology. The overall survival was 30.07. Actuarial survivals at 1, 5, and 10 years were 82%, 77%, and 62%, respectively. Six retransplants occurred among the seven graft losses albeit with poor survival after the second graft. Most explants showed low pTNM stages with favorable microscopic features. Preoperative imaging tests failed to achieve an accurate diagnosis in 15.38% of the series. The role of alpha-fetoprotein (AFP) and hepatic biopsy was irrelevant. Unfavorable histopathologic factors predicted a greater recurrence rate, but had no influence on survival. Neither recurrence nor survival were modified by pre-OLT therapy. CONCLUSIONS: In our series, AFP, hepatic biopsy, and pre-OLT treatment had limited roles. Radiological imaging techniques underestimated HCC staging and lead to a misdiagnosis to an expected degree. Despite these findings, this single institution experience with OLT for HCC showed excellent survivals with a low recurrence rate including cases of patients beyond the Milan criteria.