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Background: Liver transplantation (LT) is a curative treatment for patients with hepatocellular carcinoma who are not candidates for resection. Despite the generalized use of the Milan criteria and up-to-seven criteria, new markers have been proposed to predict recurrence after LT. Biomarkers such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), and scores such as the Model of Recurrence After Liver transplantation (MORAL) are used as predictors of post-LT recurrence., Objective: We aim to compare NLR, PLR, and MORAL score with Milan criteria and up-to-seven criteria., Methods: A descriptive study of 99 patients who underwent LT for hepatocellular carcinoma in our hospital between April 2010 and April 2016. The 5 prognostic models were applied to the patients to stratify them into risk groups. We used a Kaplan-Meier survival plot to measure recurrence-free survival in each model. Receiver operative curves were used to compare the models., Results: Three-year recurrence-free survival in MORAL was 91.1% for the low-risk group, 89.8% for the moderate-risk group, 60% for the high-risk group, and 75% for the very high-risk group (P = .003). The combined MORAL score was superior in predicting 1- and 3-year recurrence with the area under the curve 0.684 (95% confidence interval [CI]: 0.52-0.85) compared with Milan (0.536 [95% CI: 0.37-0.70]), up-to-seven (0.601 [95% CI: 0.43-0.77]), PLR (0.452 [95% CI: 0.30-0.61]), and NLR (0.542 [95% CI: 0.37-0.71])., Conclusions: A model based only on pre-LT radiological signs leads to underdiagnosis of tumor load; therefore, the risk of recurrence must be recalculated after LT. The combined MORAL score was the best prognostic model of 1- and 3-year recurrence after LT in our study., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Tumor load is often underdiagnosed on radiological examination previous to liver transplantation (LT) for hepatocarcinoma (CHC). Thus, post-liver transplant explant analysis is required following transplantation to assess the risk of the recurrence of CHC. The objectives were to compare the characteristics of CHC on pre-LT radiological examination and explant histology and validate three models for the prediction of recurrence based on data from a cohort of patients treated in our hospital., Methods: A retrospective study was undertaken of 105 LTs for CHC performed in our unit between January 2006 and January 2015. The minimum follow-up was five years. The preoperative radiological tumor stage was compared to the explant-based histologic stage. Three prognostic models were validated using our cohort of patients., Results: Following Milan's criteria, the tumor load was underdiagnosed on pre-LT radiological examination in 20 patients, which accounted for 19% of the total sample. The 5-year overall recurrence was 6.6% for scores <4 and 33.3% for scores ≥4 according to Decaens' model; 7% for scores ≤7 and 25% for scores >7 in the Up-to-Seven model; and 3.6% for PCRS ≤0, 27.8% for PCRS1-2, and 100% for PCRS≥3 according to Chan's model. The predictive model for 5-year recurrence after LT with the greatest area under the curve was Chan's model (0.813 [95% CI: 0.650-0.977]) versus Decaens' model (0.674 [95% CI: 0.483-0.866]) and the Up-to-Seven model (0.481 [95% CI: 0.296-0.667])., Conclusions: A pre-LT radiological examination leads to the underdiagnosis of tumor load, and the risk for recurrence must be recalculated following LT. In light of the results obtained, Chan's model is more accurate in predicting 5-year recurrence of CHC post-LT based on 3 levels of risk. New prognostic models are needed to optimize the prediction of recurrence after liver transplantation for hepatocarcinoma., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: The expansion of criteria for hepatocellular carcinoma (HCC) liver transplantation should produce satisfactory outcomes in terms of survival and recurrence., Objectives: To investigate if the up-to-7 criteria are applicable to liver transplantation for HCC., Methods: A review of all liver transplantations performed at our unit between January 2002 and December 2010 was conducted (645 patients). The 91 patients of the sample who had HCC were divided into 3 groups: in Milan criteria (MC; n = 74), in up-to-7 criteria (UTSC; n = 12), and outside of up-to-7 criteria (OUTSC; n = 5). A descriptive retrospective study was carried out to analyze the characteristics of liver tumors and recipients and to estimate recurrence and survival rates for this population of patients., Results: The characteristics of transplant recipients of the 3 groups were comparable. Statistically significant differences were observed in the number of tumors (1 ± 0.65 for MC, 3 ± 1.05 for UTSC, 6 ± 4.10 for OUTSC; P < .001), largest tumor size (2.47 ± 1.12 cm for MC, 3.78 ± 0.04 cm for UTSC, 4.04 ± 1.73 cm for OUTSC; P < .001), and recurrence (5.4% for MC; 33.3% for UTSC; 20% for OUTSC; P = .008). Survival rates (MC, UTSC, and OUTSC) at 3 and 5 years were 71.6%, 66.7%, and 60%, and 58.1%, 58.3%, and 40%, respectively, whereas tumor-free survival rates were 70.3%, 58.3%, and 60%, and 58.1%, 50%, and 40%, respectively., Conclusions: Survival in patients with HCC transplanted under up-to-7 criteria is acceptable. However, the expansion of criteria involves an increase in the number of patients included in the waiting list and a higher probability of relapse., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to assess the efficacy and safety of a de novo immunosuppressive regimen with everolimus (EVL) plus mycophenolate mofetil (MMF) without calcineurin inhibitors (CNI) for liver transplantation. The secondary purpose was to compare the renal function with a control group of patients treated with tacrolimus plus MMF., Methods: Sixteen male and 4 female liver transplant patients received immunosuppression with EVL plus MMF without CNI, with induction with steroids and 16 with basiliximab also. In 10 cases it was indicated as induction immunosuppression without CNI as prevention against nephrotoxicity and neurotoxicity or recurrence of hepatocarcinoma in predisposed patients and in another 10 after withdrawing CNI during the immediate post-transplant period, before hospital discharge, as the result of toxicity, mainly nephrotoxicity and neurotoxicity or the presence of hepatocarcinoma with a high risk of recurrence. A control group comprising 31 patients taking tacrolimus plus MMF was included to compare the renal function., Results: The mean follow-up time was 24 months. One patient had a recurrence of hepatocarcinoma at 8 months after transplant. The cases of nephrotoxicity and neurotoxicity resolved favorably. There were 7 rejections (35%); 2 evolved to chronic rejection with both needing retransplantation, 2 resolved with dose adjustment, and 3 required conversion to CNI. The side effects were hyperlipidemia (25%), wound dehiscence (10%), lymphedema (10%), cytomegalovirus infection (25%), myelotoxicity (25%) and proteinuria >1 g in 1 case (5%). No differences were found in renal function between the two groups., Conclusions: This regimen was proven to be efficient to prevent and treat nephrotoxicity and neurotoxicity with an acceptable tolerability profile. However, the high associated rejection rate indicates that great caution is required in its use during the immediate post-transplant period. It is advisable to associate the regimen with low doses of CNI and to have agile methods available to monitor EVL to enable rapid dose adjustment., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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.

Objective: To evaluate the results of liver transplantation (OLT) performed for hepatocellular carcinoma (HCC) among a multicenter cohort of patients with predefined common inclusion and priorization criteria., Patients and Methods: Over a 5-year period (January 2002-December 2006), 199 HCC patients underwent OLT in four centers in Andalusia. The morphological (Milan) inclusion criteria were priorized in two consecutive periods, according to the Model for End-stage Liver Disease score: group I, 53 patients (HCC < 2 cm = 24 points; > or = 2 cm or multinodular = 29 points) and group II, 146 cases (HCC < 3 cm without priorization; HCC > or = 3 cm or multinodular = 18 points)., Results: Among the 199 HCCs, 186 (93.5%) subjects were transplanted and 13 (6.5%) were excluded. There were 18 cases (9.7%) where the diagnosis was incidental and 168 were known HCC cases; 144 (85.7%) complied with the Milan criteria (Milan+); 24 (14.3%) exceeded there criteria (Milan-). According to preoperative imaging, the number of nodules and tumor mean sizes among the excluded-Milan+ and Milan- groups-were 1.8/5.3 cm, 1.4/3.5 cm, and 2.3/6.7 cm, respectively (P < .001). Percutaneous treatment during listing was delivered to 55% of the excluded cases: 49% of Milan+ and 96% of Milan-. The median time on the list was 88 days for known HCC (53 days for group I, and 97 days for group II), and 172 days for the incidental HCCs. Staging (pTNM) was correct in 64% of cases: 23% were understaged and 13% were overstaged. Overall mortality within the first 90 days was 9%, and transplant patient survival at 5 years was 61%. No differences were observed in survival rates between both study periods, although there were differences between the Milan+ (65%) and Milan- (23%) groups (P < .04). In addition, the difference in the recurrence rates was also significant between the Milan+ (7%), Milan- (24%), and the incidental (25%) groups (P < .02)., Conclusions: A common priorization policy of HCC for OLT based on morphological criteria results in a low exclusion rate on the waiting lists (6.5%). The Milan criteria are still a good cutoff to stratify the risk of recurrence, despite preoperative tumor staging being correct in only two-thirds of cases.

Introduction: Hepatocellular carcinoma is a frequent complication of cirrhosis. Liver transplantation is a valid therapeutic option for this disease providing that certain morphologic selection criteria (Milan criteria) are fulfilled., Objective: To evaluate the accuracy of pretransplantation imaging examinations in the detection and characterization of neoplastic lesions in cirrhotic candidates for liver transplantation., Patients and Method: We performed a retrospective study of 250 cirrhotic patients who underwent liver transplantation. The preoperative radiological diagnosis was compared with the definitive pathological diagnosis, allowing the diagnostic sensitivity of the different techniques, as well as the degree of agreement between pre- and postoperative tumoral staging, to be identified., Results: Analysis of 250 specimens from total hepatectomy identified 58 patients with hepatic tumors, with a total of 136 nodules. Fifty-three patients had hepatocarcinoma, nine of which were found incidentally. There were six radiological false positive diagnoses. Sixty-two percent of patients with hepatocarcinoma had multiple lesions. The most sensitive technique for the diagnosis of tumors smaller than 1 cm was magnetic resonance imaging. Agreement between pre- and postoperative staging was found in only 63.6% of cases; consequently, 43% of the patients who exceeded the Milan criteria (20% stage T3 and 23% stage T4a) underwent transplantation., Conclusions: Currently used imaging techniques lead to a substantial proportion of incorrect stagings in terms of the size and number of lesions in cirrhotic patients.

Endometriosis, defined as the presence of endometrial tissue outside the uterine cavity, is most frequently located in the pelvic organs. Hepatic endometriosis is extremely rare, and only 12 cases have previously been reported. A wide variety of symptoms have been described, from asymptomatic masses (incidental findings) to acute abdomen. The diagnostic method of choice is abdominal CT, which should always be used in the differential diagnosis of cystic liver masses. Because of the high percentage of malignant transformation, the first-line treatment is surgical resection with adequate safety margins. We report a case of in situ adenocarcinoma arising in a hepatic endometrioma, which was treated with right hepatectomy.

Introduction: Liver transplantation is currently the best therapeutic option for small hepatocellular carcinoma (HC) in selected cirrhotic patients. The main aim of this study was to analyze the results of a recent series of liver transplant cirrhotic patients with small HC applying strict preoperative selection criteria., Patients and Methods: During a period of 6 years we performed 53 liver transplants with a final diagnosis of HC on cirrhosis. The selection criteria for liver transplantation (LT) by modern imaging techniques were the Milan criteria (TNM I and II of the modified classification)., Results: Of the 53 patients, 44 (83%) were transplanted with preoperatively known HC, and 9 (17%) with incidental HC. The mean time on the waiting list was 74 +/- 62 days. Despite using strict selection criteria, 23 patients (43%) exceeded the Milan criteria in the specimen and 17 (32%) even exceeded the extended criteria of the UCSF. With a mean follow-up of 2 years, only two patients have developed recurrences. The overall survival at 1, 3, and 5 years was 80%, 70%, and 70%, respectively. The survival of patients that exceeded the Milan or USF criteria at 1, 3, and 5 years was 72% and 76%; 67% and 69%; 67% and 69%, respectively., Conclusions: The results of liver transplantation for HC are excellent when applying strict preoperative selection criteria. The current imaging methods lead to a considerable infrastaging percentage (30% to 40%), extending the indications for liver transplant due to HC beyond the scope that clinical reports would justify.

Objective: To assess the real utility of orthotopic liver transplantation (OLT) in patients with cholangiocarcinoma, we need series with large numbers of cases and long follow-ups. The aim of this paper is to review the Spanish experience in OLT for hilar and peripheral cholangiocarcinoma and to try to identify the prognostic factors that could influence survival., Summary Background Data: Palliative treatment of nondisseminated irresectable cholangiocarcinoma carries a zero 5-year survival rate. The role of OLT in these patients is controversial, due to the fact that the survival rate is lower than with other indications for transplantation and due to the lack of organs., Methods: We retrospectively reviewed 59 patients undergoing OLT in Spain for cholangiocarcinoma (36 hilar and 23 peripheral) over a period of 13 years. We present the results and prognostic factors that influence survival., Results: The actuarial survival rate for hilar cholangiocarcinoma at 1, 3, and 5 years was 82%, 53%, and 30%, and for peripheral cholangiocarcinoma 77%, 65%, and 42%. The main cause of death, with both types of cholangiocarcinoma, was tumor recurrence (present in 53% and 35% of patients, respectively). Poor prognosis factors were vascular invasion (P < 0.01) and IUAC classification stages III-IVA (P < 0.01) for hilar cholangiocarcinoma and perineural invasion (P < 0.05) and stages III-IVA (P < 0.05) for peripheral cholangiocarcinoma., Conclusions: OLT for nondisseminated irresectable cholangiocarcinoma has higher survival rates at 3 and 5 years than palliative treatments, especially with tumors in their initial stages, which means that more information is needed to help better select cholangiocarcinoma patients for transplantation.

Orthotopic liver transplantation (OLT) offers the only chance to eliminate both tumor and liver disease in patients with hepatocellular carcinoma (HCC) and cirrhosis. However, tumor progression while on the waiting list and recurrence after OLT are frequent. We undertook a large multicenter study to assess survival and related factors of recurrence after OLT. This retrospective study analyses data from 307 consecutive patients with HCC and cirrhosis treated with OLT between 1990 and 1997 in eight centers in Spain. OLT was indicated only for small (<5 cm) localized tumors. Five-year rates after OLT were 63% for survival, 58% for disease-free survival, and 21% for recurrence. Tumor diameter larger than 5 cm was associated with other tumor characteristics that were significant indicators of poor outcome (absence of capsule, three or more nodules, bilobularity, satellite nodules, and vascular invasion). However, in multivariate analysis, alpha fetoprotein (AFP) levels greater than 300 ng/mL (P = .04; P = .02) and macroscopic vascular invasion (P = .01; P = .0001) were the only factors independently associated with mortality and recurrence, respectively. OLT is indicated in patients with small HCCs who have low AFP levels and no macroscopic vascular invasion or extrahepatic disease. By increasing our ability for preoperative tumor imaging, we will achieve better selection of patients with HCC before OLT.

The molecular basis of porphyria cutanea tarda is defective activity of hepatic uroporphyrinogen decarboxylase. A common characteristic is liver dysfunction than goes from cirrhosis to hepatocellular carcinoma. A high prevalence of hepatitis C virus markers has been demonstrated. We study a patient with PCT and hepatitis C virus markers that finally develops to hepatocellular carcinoma without previous cirrhosis. Previous studies with association of PCT and hepatitis C virus markers, have found liver diseases ranging from cirrhosis to hepatocellular carcinoma. The importance of this study is the absence of cirrhosis.

We present a case of hepatic myelolipoma that was treated by performing a right hepatic lobectomy. These tumors are very uncommon and present great problems for the pre-operative diagnostic evaluation. Currently, the diagnosis is essentially histopathological with a definitive diagnosis being made by immunocytochemical staining. We have found no reports on this type of tumor in the Spanish literature; a review of the published cases confirms our observations and conclusions regarding hepatic myelolipoma.

Over a period of 6.5 years, 29 patients with liver hemangiomas have been examined. In 8 patients, the most frequent symptom was pain; in 11, a tumor was found. The diagnosis was made by means of scintigraphy with 99mTc, followed by real-time sonography, computed tomography using a contrast medium, and selective arteriography. In 16 patients (15 women, 1 man), the tumor radius was more than 6 cm and in 9 of these, more than 10 cm. In 3 patients, a left lobectomy was carried out, and in 5 a right lobectomy; in an additional 5 patients, a extended right lobectomy (three segments excised) was done. In the rest, a medial lobectomy, a segmentectomy on the left side, or a segmentectomy on the right was performed. The only complications observed in the whole series were: pleural effusion (1 case), subphrenic abscess (1), and transitory biliary fistula (1). All hemangiomas with a radius of more than 10 cm should be removed operatively, as should smaller symptomatic hemangiomas and tumors that are not clearly benign.