Transarterial chemoembolization is the most common treatment used for HCC patients on liver transplant waiting list. The aims of this study are to evaluate the radio-histological correlation of the post-chemoembolization HCC response and its influence on overall survival (OS) and recurrence-free survival (RFS).

Monocentric, retrospective study, including liver transplant patients with HCC who received chemoembolization from 2007 to 2018. The response of the hypervascular nodules was evaluated according to mRECIST, EASL.

A total of 70 patients with 122 hypervascular and 28 hypovascular HCCs were included. A complete radiological response concerned 34.3% patients. Concordance rates of hypervascular nodules (mRECIST, EASL and lipiodol uptake) with tumor necrosis ranged from 49% to 57%, with a specificity of 35% and a positive predictive value of 54%. Bilobar involvement was a predictive factor for incomplete radiological response. Major tumor necrosis was significantly correlated with the decrease in αFP level between the first CEL and liver transplantation. OS and RFS at 5 years were 64% and 60%, respectively, and 69% and 66% at complete radiological response.

Radiological response is significantly related to histological tumor necrosis, but with poor prediction. In case of complete radiological response, OS and RFS seem to be improved.

Patients with hepatocellular carcinoma (HCC) are selected for transplantation if they have a low tumour burden and low risk of recurrence. The morphometric Milan criteria have been the cornerstone for patient selection, but dynamic morphological and biological tumour characteristics surfaced as an encouraging tool to refine the selection of patients with HCC and to support the expansion of the Milan criteria. The outcomes of the most prevalent models that select patients with HCC for liver transplantation were analysed in this study, which aimed to identify the selection model that offered the best recurrence-free and overall survival after transplantation.

Studies that compared Milan, University of California San Francisco (UCSF), up-to-seven (UPTS), alpha-fetoprotein (AFP), and MetroTicket 2.0 (MT2) models were included. One-year, 3-year, and 5-year recurrence-free and overall survival rates of patients selected for transplantation using different models were analysed.

A total of 60 850 adult patients with HCC selected for liver transplantation using Milan, UCSF, UPTS, AFP, or MT2 criteria were included. Patients selected for transplantation using the MT2 model had the highest 1-, 3-, and 5-year recurrence-free survival. In addition, patients selected for transplantation using MT2 criteria had the best 1- and 3-year overall survival, whereas patients selected for transplantation using the Milan criteria had the best 5-year overall survival rates.

The MT2 model offered the best post-transplant outcomes in patients with HCC, highlighting the importance of considering tumour morphology and biology when selecting patients with HCC for liver transplantation.

Hepatocellular carcinoma (HCC) is the most commonly diagnosed primary liver tumor with an increasing incidence worldwide. Management of patients with HCC is largely dictated by the presence of cirrhosis, disease stage, underlying liver function, and patient performance status.

We provide an update on key aspects of surgical treatment options for patients with HCC. RESULTS & CONCLUSIONS: Liver resection and transplantation remain cornerstone treatment options for patients with early-stage disease and constitute the only potentially curative options for HCC. Selection of patients for surgical treatment should include a thorough evaluation of tumor characteristics and biology, as well as evidence-based use of various available treatment options to achieve optimal long-term outcomes for patients with HCC.

Liver transplantation is the main treatment for hepatocellular carcinoma (HCC). However, because of the limited supply of transplant organs, it is necessary to adopt a criterion that selects patients who will achieve adequate survival after transplantation. The aim of this review is to compare the two main staging criteria of HCC for the indication of liver transplantation (Milan and UCSF) and to analyze the post-transplantation survival rate at 1, 3 and 5 years.

This is a systematic review and meta-analysis in which scientific articles from 5 databases (PubMed, Lilacs, Embase, Central, and Cinahl) were analyzed. The studies included in the review consisted of liver transplantation in patients with HCC in different subgroups according to donor type (deceased × living), population (eastern × western) and tumor evaluation (radiological × pathological) and adopted the Milan or UCSF criteria for the indication of the procedure.

There was no significant difference between the Milan and UCSF criteria in the overall survival rate at 1, 3 or 5 years, and the overall estimated value found was 1.03 [0.90, 1.17] at 1 year, 1.06 [0.96, 1.16] at 3 years and 1.04 [0.96, 1.12] at 5 years. Regarding the analysis of the subgroups, no significant difference was observed in any of the subgroups with a follow-up of 1, 3 or 5 years.

Both the Milan and UCSF criteria have equivalent survival rate. Thus, less restrictive method would not result in a great loss in the final overall survival rate and would benefit a greater number of patients.

Living donor liver transplantation (LDLT) is an established treatment for patients with cirrhosis and hepatocellular carcinoma (HCC) within Milan criteria. Acceptable outcomes have been demonstrated in patients fulfilling extended criteria. Here, we share our experience with LDLT for patients with HCC within and beyond Milan criteria, with emphasis on poor prognostic factors.

We retrospectively reviewed patients who underwent LDLT between 2012 and 2017 and had HCC proven on explant liver histopathology. A total of 117 patients were included. Patients who died early after transplant (in <30 days) were excluded. For outcomes, patients were divided into prognostic groups. These groups were based on (1) alpha fetoprotein >600, (2) poor differentiation, and (3) the presence of lymphovascular invasion. Recurrence-free survival (RFS) was determined using Kaplan-Meier curves.

Median age was 53 (30-73) years. Median follow-up was 20.3 (1-63.2) months. Median model for end stage liver disease (MELD) score was 19 (9-34). Of a total of 117 patients, 74 (63.2%) patients met Milan criteria. Recurrence rate was 12/117 (10.3%). Actuarial 5-year RFS was 88% and 82% (P = 0.3) in patients within and outside Milan criteria. There was no difference in 3-year RFS in patients with 0, 1, or 2 poor prognostic factors within Milan criteria (92%, 87%, and 75%, respectively; P = 0.3). However, a significant difference in RFS was seen in patients outside Milan criteria (92%, 93%, and 53%; P = 0.03).

Patients within Milan criteria have acceptable RFS even in the presence of poor prognostic factors. However, the presence of two or more poor prognostic variables significantly impacts RFS of patients outside Milan criteria.

Hepatocellular carcinoma (HCC) is an aggressive malignant neoplasm that is often chemoresistant. Complete surgical resection remains the mainstay of therapy. The role of liver transplantation (LT) in pediatric HCC is in evolution, as is the role of adjuvant chemotherapy for stage I disease.

A retrospective review of patients < 18 years of age with completely resected HCC treated with surgical intervention alone at our institution from 2004 to 2015 was conducted.

Twelve patients with a median age of 12 years (range = 1-17; number of females = 7) with upfront resected HCC (Evans stage I) were identified. Four patients had HCC without identifiable risk factors (fibrolamellar-HCC = 2; early HCC arising in focal nodular hyperplasia = 1, well-differentiated [wd] HCC = 1). Four patients had early or wd-HCC in the context of portosystemic shunts (Abernethy = 2; mesocaval shunt and portal vein thrombosis = 2). Four patients had moderate to wd-HCC in the context of pre-existing liver disease with cirrhosis (progressive familial intrahepatic cholestasis type-2 = 2, alpha-1 antitrypsin deficiency = 1, Alagille syndrome = 1). Seven patients underwent LT (multifocal = 5; solitary = 2); five exceeded Milan criteria (MC) by imaging. Five patients underwent complete resection (segmentectomy = 2; hemihepatectomy = 3). Ten patients received no adjuvant chemotherapy. All patients are alive without evidence of disease with a median follow-up of 54.1 months (range = 28.1-157.7 months).

Pediatric and adolescent patients with upfront, completely resected HCC can be effectively treated without chemotherapy. LT should be considered for nonmetastatic HCC, especially in the context of pre-existing chronic liver disease, even when the tumor exceeds MC. Distinct pediatric selection criteria are needed to identify patients most suitable for LT.

Milan criteria are used for patient selection in liver transplantation for hepatocellular carcinoma (HCC). Hangzhou criteria have been shown in China to enable access to liver transplantation for more patients when compared to Milan criteria without negative effects on long-term survival. The purpose of this study was to evaluate the Hangzhou criteria in a German cohort.

One hundred fifty-nine patients transplanted for HCC between 1975 and 2010 were investigated. Patients were categorized into four groups depending on the fulfillment of Milan and Hangzhou criteria. General and tumor baseline characteristics were compared. Overall and tumor-free survival rates were investigated with the Kaplan-Meier analysis.

One-, 3-, 5-, and 10-year survival rates for patients fulfilling Milan criteria (n = 68) were 89.7, 83.7, 75.8, and 62.1%, respectively, versus 89.8, 82.2, 75.2, and 62.6% for patients fulfilling Hangzhou criteria (n = 109) (p = 0.833). When comparing patients exceeding Milan or Hangzhou criteria, survival rates were 75.3, 53.2, 48.1, and 41.1% versus 63.3, 31.4, 26.9, and 22.1%, respectively (p = 0.019). The comparison of tumor-free survival rates in patients fulfilling Milan or Hangzhou criteria was statistically not significant (p = 0.785), whereas the comparison of the groups exceeding the criteria showed significantly worse survival for patients outside Hangzhou criteria (p = 0.007). The proportion of patients fulfilling Hangzhou criteria (68.6%) was significantly larger as compared to the proportion fulfilling Milan criteria (42.8%) (p < 0.001).

Hangzhou criteria are more accurate in predicting long-term survival after liver transplantation for HCC in Germany. Deployment of the Hangzhou criteria for patient selection could enlarge the pool of transplantable patients.

Survival after orthotopic liver transplantation (LT) for hepatocellular carcinoma (HCC) is influenced by tumor recurrence. This study examines the survival of patients who underwent LT for HCC and developed recurrence of tumor after transplantation.

A retrospective analysis was performed of the 200 patients who underwent LT secondary to HCC from 1990 to 2014. We excluded 19 patients from the study owing to early postoperative deaths in the 1st month. We divided our sample into 2 groups according to the presence of recurrence. We performed a univariate analysis to identify variables that are significantly associated with the risk of recurrence. Afterward we use multivariate analysis regression analysis to find independent significance.

Univariate analysis shows significant relationship between high Edmondson-Steiner grades (G3-G4) and the development of tumor recurrence. Tumor size, vascular invasion, and capsular invasion were found to be independent risk factors of tumor recurrence in the multivariate analysis.

Tumor recurrence defines survival of patients who underwent LT for HCC. In this study we discuss which histologic factor are associated with higher risk of tumor recurrence, and therefore a negative the impact on patient's survival.

Liver transplant performed for hepatocellular carcinoma must adhere to criteria for the size and number of focal hepatic lesions to lower the incidence of recurrence and achieve survival rates comparable to patients transplanted for other indications. Since the Milan criteria were established in 1996, there have been many less restrictive criteria yielding similar results. Our aim was to identify the prognostic factors for patient survival and for recurrence of hepatocellular carcinoma for patients within and beyond the Milan criteria.

This retrospective and prospective analysis was conducted in 60 adult patients who underwent right lobe living-donor liver transplant for cirrhosis complicated by hepatocellular carcinoma at Dar Al Fouad Hospital, 6th of October City, Egypt, between August 2001 and June 2012. The median follow-up was 39.5 months.

Overall 1-, 3-, and 5-year survival rates were 98.3%, 93.5%, and 71.4%. Overall disease-free survival rates at 1, 3, and 5 years were 96.6%, 93.5%, and 64.2%. There was no statistically significant difference in overall survival time between patients within and beyond the Milan criteria. Factors affecting recurrence were the tumor grade, lobar distribution, size of the largest nodule, and the total tumor burden in the explanted liver. Recurrence adversely affected survival.

Using our criteria of a single tumor ≤ 6 cm, or 2 to 3 tumors with the largest ≤ 4.5 cm, or 4 to 5 tumors with the largest ≤ 3 cm and total tumor size ≤ 8 cm resulted in overall survival comparable to patients within the Milan criteria.

Liver transplantation (LT) is a well-established option of cure for hepatocellular carcinoma (HCC). Milan criteria is recognized as standard for selection of patients and set the baseline of survival to be achieved. It has been shown that tumor biology including differentiation, vascular invasion, and serum α-fetoprotein (AFP) predict posttransplant recurrence and survival better than morphology. Downstaging by locoregional therapies of HCC before LT, with the response to treatments and progression within observation period, serves as a selection tool rather than modulation of tumor biology. It selects those patients outside standard criteria at presentation but good tumor biology and high chance of good outcome to receive transplantation. The definition of downstaging should be differentiated from neo-adjuvant therapy, and the objectives in surgical and pretransplant candidates also differ.Published studies in this area showed variation in inclusion criteria, downstaging protocol and assessment of successful downstaging. Tumor biology predownstaging and postdownstaging was not incorporated. Posttransplant outcome were not clearly stated with regard to intention-to-treat survival, disease-free survival, and comparison against those originally within criteria. Meta-analysis of these results was impossible. Nevertheless, majority had reasonable protocol and were able to select patients whom likely to have good outcome. At present, there is no evidence that downstaged patients have a poorer prognosis than those presenting within the Milan criteria. Patients with tumors outside Milan criteria should be offered downstaging therapies. Those who are successfully downstaged to within Milan criteria should be eligible to liver transplant as same as those initially fit the criteria. In the last decade, various extended criteria of HCC for LT have been proposed and reported satisfactory survival. That makes downstaging technically unnecessary.To refine and validate the role of downstaging, it needs collaborative and prospective study with significant sample size, adequate preoperative staging, standardized protocol of selection of patients, and approaches to downstaging. Selection criteria should include histopathological data on tumor biology and serum AFP. There should be standardized definition of successful downstaging. Posttransplant disease-free survival should be reported in detail and compared with those who fit the standard criteria initially. A consistent immunosuppressant protocol is important to avoid bias.

The implementation of the Milan criteria (MC) in 1996 has dramatically improved prognosis after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Liver transplantation has, thereby, become the standard therapy for patients with "early-stage" HCC on liver cirrhosis. The MC were consequently adopted by United Network of Organ Sharing (UNOS) and Eurotransplant for prioritization of patients with HCC. Recent advancements in the knowledge about tumor biology, radiographic imaging techniques, locoregional interventional treatments, and immunosuppressive medications have raised a critical discussion, if the MC might be too restrictive and unjustified keeping away many patients from potentially curative LT. Numerous transplant groups have, therefore, increasingly focussed on a stepwise expansion of selection criteria, mainly based on tumor macromorphology, such as size and number of HCC nodules. Against the background of a dramatic shortage of donor organs, however, simple expansion of tumor macromorphology may not be appropriate to create a safe extended criteria system. In contrast, rather the implementation of reliable prognostic parameters of tumor biology into selection process prior to LT is mandatory. Furthermore, a multidisciplinary approach of pre-, peri-, and posttransplant modulating of the tumor and/or the patient has to be established for improving prognosis in this special subset of patients.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in the world. Early detection and timely treatment of HCC is critical for better patient outcomes. Curative therapy consists of surgical hepatic resection or liver transplantation (LTx); however, both are restricted to explicit selective criteria. Liver resection is the gold standard of treatment for noncirrhotic patients but can be done in only a small fraction of cirrhotic patients depending on synthetic dysfunction, degree of portal hypertension, and number and location(s) of tumor(s). Therefore, the best treatment modality in cirrhotic patients with HCC is LTx as it will cure both HCC and the underlying cirrhosis. The limitation to offer transplant to all cirrhotic patients with HCC is the shortage of available donor organs. While these patients are waiting for transplant, their tumors may progress and develop distant metastases and may lead to patients losing their candidacy for LTx. Various ablation therapies can be used to treat HCC, prevent tumor progression, and thus, avoid patients losing the option of LTx. Future directions to improve HCC patient outcomes include advancement in tumor gene analysis and histopathology for better prediction of tumor behavior, improved immunosuppression regimens to reduce tumor recurrence in the posttransplant setting, and efficient use of an expanded donor pool that includes living donor organs. This paper will review the current methods of HCC diagnosis, selection for either hepatic resection or LTx, and will also summarize posttreatment outcomes. We will suggest future directions for the field as we strive to improve outcomes for our HCC patients.

Preoperative α-fetoprotein (AFP) levels may have an influence on disease-free survival (DFS) of patients after liver transplantation for hepatocellular carcinoma (HCC) located on a cirrhotic liver.

Between 2000 and 2009, two groups were distinguished according to preoperative AFP level: normal-level group (<10 ng/ml) and increased-level group (>10 ng/ml). The increased-level group was further divided into three levels of preoperative AFP: 10-150, 150-500, and ≥ 500 ng/ml. DFS and recurrence rates were compared. All patients underwent transplantation using the preoperative 5/5 criteria.

Of the 122 patients in this study, 63 had normal and 59 had increased preoperative AFP. There were no differences between the two groups concerning perioperative or pathologic data. Those with an increased preoperative AFP level had a significantly shorter 5-year DFS, and their recurrence rate was higher than that of the normal AFP group. The 5-year DFS and recurrence rates were 71 and 4 %, respectively, for those with normal AFP; 57 and 10 %, respectively, for those with AFP 10-150 ng/ml; 46 and 24 %, respectively, for those with AFP 150-500 ng/ml; and 28 and 62 %, respectively, for those with AFP ≥ 500 ng/ml.

This study shows the prognostic value of preoperative AFP levels on DFS after a liver transplant for HCC in a population of patients undergoing transplantation with the same preoperative criteria.

Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality worldwide. Liver transplantation offers a potential cure for this otherwise devastating disease. The selection of the most appropriate candidates is paramount in an era of graft shortage.

To review systematically the role of liver transplantation in the management of HCC in current clinical practice.

An electronic literature search using PUBMED (1980-2010) was performed. Search terms included HCC, hepatoma, liver cancer, and liver transplantation.

Liver transplantation is a highly successful treatment for HCC, in patients within Milan criteria (MC), defined as a solitary tumour ≤50 mm in diameter or ≤3 tumours ≤30 mm in diameter in the absence of extra-hepatic or vascular spread. Other eligibility criteria for liver transplantation are also used in clinical practice, such as the University of California, San Francisco criteria, with outcomes comparable to MC. Loco-regional therapies have a role in the bridging treatment of HCC by minimising wait-list drop-out secondary to tumour progression. Beyond MC, encouraging results have been demonstrated for patients with down-staged tumours. Post-liver transplantation, there is no evidence to support a specific immunosuppressive regimen. In the context of an insufficient cadaveric donor pool to meet demand, the role of adult living donation may be increasingly important.

Liver transplantation offers a curative therapy for selected patients with HCC. The optimisation of eligibility criteria is paramount to ensure that maximum benefit is accrued. Although wait-list therapies have been incorporated into clinical practice, additional high quality data are required to support this strategy.

The application of orthotopic liver transplantation (OLT) for patients with hepatocellular cancer (HCC) necessitates highly selective criteria to maximize survival and to optimize allocation of a scarce resource. The objective of this study was to compare the outcomes of OLT for HCC in patients transplanted under Milan and UCSF criteria. The United Network of Organ Sharing (UNOS) database was queried for patients who had undergone OLT for HCC from 2002 to 2007, and 1,972 patients (Milan criteria, n = 1, 913; UCSF criteria, n = 59) were identified. Patients were stratified by pretransplant criteria (Milan versus UCSF), and clinical and pathologic factors and overall survival were compared. There were no differences in age, gender, diabetes mellitus, body mass index, and hepatitis B, or C status between the two groups. Overall survival was similar between the Milan and UCSF cohorts (1-, 2-, 3-, and 4-year survival rates: 88%, 81%, 76%, and 72% versus 91%, 80%, 68% and 51%, respectively, P = 0.21). Although the number of patients within UCSF criteria was small, our results nevertheless suggest that patients with HCC may have equivalent survival when transplanted under Milan and UCSF criteria. Long-term followup may better determine whether UCSF criteria should be widely adopted.

A majority of patients with hepatocellular carcinoma (HCC) undergoing liver transplantation (LT) meet the Milan criteria, but these are still regarded as the narrowest criteria for transplantation. Prognostic analysis of incidentally detected HCC after LT suggests that a subgroup of HCC patients is at very low risk of recurrence. To determine the criteria defining this super-selection group, we retrospectively analyzed survival data of 593 adult living-donor LT recipients with HCC in the explanted liver

Tumor features of incidental HCC in 38 patients not showing recurrence were analyzed. Of these patients, 34 (89.5%) each had ≤2 tumors and tumors ≤2.0 cm in size. Applying these criteria to 555 patients with pretransplant known HCC (pkHCC) allowed us to identify 79 patients with untreated pkHCCs ≤2.0 cm in size. To date, only two of these patients have shown recurrence, making the conditions for super-selection the presence of tumors ≤2.0 cm in size, ≤2 tumors, alpha-fetoprotein ≤200 ng/mL, and no pretransplant treatment. In 87 patients satisfying these criteria, the 10-year recurrence and survival rates were 1.3% and 92.1%, respectively. After excluding patients meeting these criteria, the 5-year recurrence rates in patients satisfying the Milan, University of California at San Francisco, and Asan criteria were increased by 2.9-4.0%. In conclusion, this super-selection or super-Milan category may be used for validation assessment of various indication criteria and for the development of cost-effective post-transplantation HCC surveillance protocols. Further studies should be followed for deceased-donor LT and patients who have undergone pretransplant treatment.

The aim of this systematic review was to assess the evidence on tumour downstaging before liver transplantation in patients with hepatocellular carcinoma (HCC) initially staged beyond the Milan criteria.

MEDLINE (from 1952), Embase (from 1980) and the Cochrane Library were searched. The review included cohort studies that reported the outcomes of patients with HCC outside the Milan criteria who underwent downstaging before transplantation.

Eight studies met the inclusion criteria and included a total of 720 patients who underwent transplantation following downstaging after initial presentation with disease outside the Milan criteria. The rate of successful downstaging varied from 24 to 69 per cent of patients. Reported survival rates ranged from 82 to 100 per cent, 79 to 100 per cent and 54·6 to 94 per cent at 1, 3 and 5 years respectively. These were comparable with results for patients presenting within the Milan criteria.

Successful downstaging of HCC to within the Milan criteria is feasible in a proportion of patients. Absolute and disease-free survival rates in patients transplanted following downstaging are comparable to those in patients within the Milan criteria.

Unresectable malignant liver tumors may be treated by LTx. We evaluated the results of LTx for HB and HCC. All patients transplanted for HB or HCC between 1990 and 2007 were included. Effects of histologic tumor type, primary tumor resection, disease staging, and serum AFP levels at diagnosis and at transplantation on disease recurrence and survival were evaluated. Twelve patients with median age of five (range, 2-16) were transplanted and followed for a median of 11 (2-18) yr. Six patients had HB and six had HCC. At diagnosis, eight patients were staged as PRETEXT III and four patients as PRETEXT IV. Two patients had pulmonary metastases. All patients received neoadjuvant chemotherapy. Median time from diagnosis to LTx was seven (2-133) months. At LTx, none of the patients had radiological evidence of extrahepatic disease, and the median AFP level was 85 (6-15 180) microg/L. No routine chemotherapy after LTx was used.The overall one-, five-, and 10-yr cumulative survival rates were 100%, 80%, and 67%, respectively. Survival was comparable between the two tumor types (4/6 for both). Two deaths occurred secondary to tumor recurrence, one of each tumor type. Both of these patients had an AFP response of <99%. Six of eight patients with primary LTx survived, when compared to two of four transplanted after primary resection. PRETEXT tumor staging had no effect on survival. LTx even without post-transplantation chemotherapy is an effective treatment option for unresectable HB and HCC with comparable survival. Incomplete AFP response to chemotherapy and primary tumor resection were associated with decreased survival.