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1
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Zhang X, Chen C, Wang Y, Xu J. Recurrence risk prediction models for hepatocellular carcinoma after liver transplantation. J Gastroenterol Hepatol 2024; 39:2272-2280. [PMID: 39113259 DOI: 10.1111/jgh.16693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 07/05/2024] [Accepted: 07/17/2024] [Indexed: 12/06/2024]
Abstract
Liver transplantation (LT) is an effective method for curing hepatocellular carcinoma (HCC). However postoperative tumor recurrence can lead to higher mortality rates. To select suitable candidates for LT, the Milan Criteria (MC) were first proposed based on tumor morphological characteristics. For those patients who meet the MC, the MC can effectively reduce the postoperative tumor recurrence rate and improve the prognosis of patients undergoing LT. It has always been internationally recognized as the gold standard for selecting candidates for LT, marking a milestone in the history of LT for HCC. However, its strict conditions exclude some HCC patients who could benefit from LT. Therefore, comprehension consideration criteria, including serum biomarkers, tumor histology, and other factor, have been continuously proposed in addition to tumor morphology. This article summaries the prediction model for HCC recurrence after LT from five aspects: tumor morphology, serum markers, histopathology, cellular inflammatory factors and downstaging treatment before transplantation. The aim is to assist clinicians in accurately assessing HCC status, selecting appropriate liver transplant candidates, maximize graft and patients' survival, and optimizing the utilization of social health resources.
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Affiliation(s)
- Xu Zhang
- Academy of Medical Sciences, Shanxi Medical University, Taiyuan, China
| | - Chi Chen
- Department of Statistics, School of Public Health, Shanxi Medical University, Taiyuan, China
| | - Yan Wang
- Hepatobiliary and Pancreatic Surgery and Liver Transplantation Center, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Jun Xu
- Hepatobiliary and Pancreatic Surgery and Liver Transplantation Center, First Hospital of Shanxi Medical University, Taiyuan, China
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2
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Attia AM, Adetyan H, Yang JD. Severity of microvascular invasion does matter in hepatocellular carcinoma prognosis: Editorial on "Classification of microvascular invasion of hepatocellular carcinoma: correlation with prognosis and magnetic resonance imaging". Clin Mol Hepatol 2024; 30:653-655. [PMID: 38946462 PMCID: PMC11540395 DOI: 10.3350/cmh.2024.0482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 06/29/2024] [Indexed: 07/02/2024] Open
Affiliation(s)
| | - Hasmik Adetyan
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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3
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Goetz A, Verloh N, Utpatel K, Fellner C, Rennert J, Einspieler I, Doppler M, Luerken L, Alizadeh LS, Uller W, Stroszczynski C, Haimerl M. Differentiating Well-Differentiated from Poorly-Differentiated HCC: The Potential and the Limitation of Gd-EOB-DTPA in the Presence of Liver Cirrhosis. Diagnostics (Basel) 2024; 14:1676. [PMID: 39125552 PMCID: PMC11311873 DOI: 10.3390/diagnostics14151676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 07/30/2024] [Accepted: 07/31/2024] [Indexed: 08/12/2024] Open
Abstract
This study uses magnetic resonance imaging (MRI) to investigate the potential of the hepatospecific contrast agent gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) in distinguishing G1- from G2/G3-differentiated hepatocellular carcinoma (HCC). Our approach involved analyzing the dynamic behavior of the contrast agent in different phases of imaging by signal intensity (SI) and lesion contrast (C), to surrounding liver parenchyma, and comparing it across distinct groups of patients differentiated based on the histopathological grading of their HCC lesions and the presence of liver cirrhosis. Our results highlighted a significant contrast between well- and poorly-differentiated lesions regarding the lesion contrast in the arterial and late arterial phases. Furthermore, the hepatobiliary phase showed limited diagnostic value in cirrhotic liver parenchyma due to altered pharmacokinetics. Ultimately, our findings underscore the potential of Gd-EOB-DTPA-enhanced MRI as a tool for improving preoperative diagnosis and treatment selection for HCC while emphasizing the need for continued research to overcome the diagnostic complexities posed by the disease.
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Affiliation(s)
- Andrea Goetz
- Department of Radiology, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Niklas Verloh
- Department of Diagnostic and Interventional Radiology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, 79085 Freiburg, Germany
| | - Kirsten Utpatel
- Department of Pathology, University Regensburg, 93053 Regensburg, Germany
| | - Claudia Fellner
- Department of Radiology, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Janine Rennert
- Department of Radiology, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Ingo Einspieler
- Department of Radiology, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Michael Doppler
- Department of Diagnostic and Interventional Radiology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, 79085 Freiburg, Germany
| | - Lukas Luerken
- Department of Radiology, Klinikum Würzburg Mitte, 97074 Würzburg, Germany
| | - Leona S. Alizadeh
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, 60596 Frankfurt am Main, Germany
| | - Wibke Uller
- Department of Diagnostic and Interventional Radiology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, 79085 Freiburg, Germany
| | | | - Michael Haimerl
- Department of Radiology, Klinikum Würzburg Mitte, 97074 Würzburg, Germany
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4
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Battistella S, Grasso M, Catanzaro E, D’Arcangelo F, Corrà G, Germani G, Senzolo M, Zanetto A, Ferrarese A, Gambato M, Burra P, Russo FP. Evolution of Liver Transplantation Indications: Expanding Horizons. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:412. [PMID: 38541138 PMCID: PMC10972065 DOI: 10.3390/medicina60030412] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 02/22/2024] [Accepted: 02/26/2024] [Indexed: 01/03/2025]
Abstract
Liver transplantation (LT) has significantly transformed the prognosis of patients with end-stage liver disease and hepatocellular carcinoma (HCC). The traditional epidemiology of liver diseases has undergone a remarkable shift in indications for LT, marked by a decline in viral hepatitis and an increase in metabolic dysfunction-associated steatotic liver disease (MASLD), along with expanded indications for HCC. Recent advancements in surgical techniques, organ preservation and post-transplant patients' management have opened new possibilities for LT. Conditions that were historically considered absolute contraindications have emerged as potential new indications, demonstrating promising results in terms of patient survival. While these expanding indications provide newfound hope, the ethical dilemma of organ scarcity persists. Addressing this requires careful consideration and international collaboration to ensure equitable access to LT. Multidisciplinary approaches and ongoing research efforts are crucial to navigate the evolving landscape of LT. This review aims to offer a current overview of the primary emerging indications for LT, focusing on acute-on-chronic liver failure (ACLF), acute alcoholic hepatitis (AH), intrahepatic and perihilar cholangiocarcinoma (i- and p-CCA), colorectal liver metastasis (CRLM), and neuroendocrine tumor (NET) liver metastases.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Francesco Paolo Russo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 Padua, Italy; (S.B.); (E.C.); (F.D.); (G.C.); (G.G.); (M.S.); (A.Z.); (A.F.); (M.G.); (P.B.)
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5
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Cabibbo G, Daniele B, Borzio M, Casadei-Gardini A, Cillo U, Colli A, Conforti M, Dadduzio V, Dionisi F, Farinati F, Gardini I, Giannini EG, Golfieri R, Guido M, Mega A, Minozzi S, Piscaglia F, Rimassa L, Romanini L, Pecorelli A, Sacco R, Scorsetti M, Viganò L, Vitale A, Trevisani F. Multidisciplinary Treatment of Hepatocellular Carcinoma in 2023: Italian practice Treatment Guidelines of the Italian Association for the Study of the Liver (AISF), Italian Association of Medical Oncology (AIOM), Italian Association of Hepato-Bilio-Pancreatic Surgery (AICEP), Italian Association of Hospital Gastroenterologists (AIGO), Italian Association of Radiology and Clinical Oncology (AIRO), Italian Society of Pathological Anatomy and Diagnostic Cytology (SIAPeC-IAP), Italian Society of Surgery (SIC), Italian Society of Gastroenterology (SIGE), Italian Society of Medical and Interventional Radiology (SIRM), Italian Organ Transplant Society (SITO), and Association of Patients with Hepatitis and Liver Disease (EpaC) - Part I - Surgical treatments. Dig Liver Dis 2024; 56:223-234. [PMID: 38030455 DOI: 10.1016/j.dld.2023.10.029] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 10/07/2023] [Accepted: 10/30/2023] [Indexed: 12/01/2023]
Abstract
Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. The remarkable improvements in treating HCC achieved in the last years have increased the complexity of HCC management. Following the need to have updated guidelines on the multidisciplinary treatment management of HCC, the Italian Scientific Societies involved in the management of this cancer have promoted the drafting of a new dedicated document. This document was drawn up according to the GRADE methodology needed to produce guidelines based on evidence. Here is presented the first part of guidelines, focused on the multidisciplinary tumor board of experts and surgical treatments of HCC.
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Affiliation(s)
- Giuseppe Cabibbo
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Italy; Gastroenterology Unit, Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone", Palermo, Italy.
| | - Bruno Daniele
- Oncology Unit, Ospedale del Mare, ASL Napoli 1 Centro, Napoli, Italy
| | - Mauro Borzio
- Centro Diagnostico Italiano (CDI), Milano, Italy
| | - Andrea Casadei-Gardini
- Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy
| | - Umberto Cillo
- General Surgery 2-Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, Padua University Hospital, 35128 Padua, Italy
| | - Agostino Colli
- Dipartimento di Medicina Trasfusionale ed Ematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | | | - Vincenzo Dadduzio
- Medical Oncology Unit, "Mons. A.R.Dimiccoli" Hospital, Barletta, ASL BT, Italy
| | - Francesco Dionisi
- Department of Radiation Oncology, IRCCS Regina Elena National Cancer Institute - Rome, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; Gastroenterology Unit, Azienda Ospedale-Università di Padova, 35128 Padova, Italy
| | - Ivan Gardini
- EpaC Onlus, Italian Liver Patient Association, Turin, Italy
| | - Edoardo Giovanni Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Rita Golfieri
- Alma Mater Studiorum" Bologna University, Bologna, Italy; Radiology Unit Madre Fortunata Toniolo Private Hospital, coordinator of Radiology centers Medipass Bologna, Bologna, Italy
| | - Maria Guido
- Department of Medicine, University of Padova, Padova- Italy
| | - Andrea Mega
- Department of Gastronterology, Regional Hospital Bolzano, Italy
| | - Silvia Minozzi
- Oncology Department, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Milano, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Lorenza Rimassa
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy; Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Laura Romanini
- Radiology Unit, Ospedale di Cremona, ASST Cremona, Cremona, Italy
| | - Anna Pecorelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Rodolfo Sacco
- Gastroenterology and Endoscopy Unit, Department of Surgical and Medical Sciences, University of Foggia, 71100 Foggia, Italy
| | - Marta Scorsetti
- Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele, Milan, Italy; Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital IRCCS, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Luca Viganò
- Hepatobiliary Unit, Department of Minimally Invasive General & Oncologic Surgery, Humanitas Gavazzeni University Hospital, Viale M. Gavazzeni 21, 24125 Bergamo, Italy; Department of Biomedical Sciences, Humanitas University, Viale Rita Levi Montalcini 4, 20090 Milan, Italy
| | - Alessandro Vitale
- General Surgery 2-Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, Padua University Hospital, 35128 Padua, Italy
| | - Franco Trevisani
- Department of Medical and Surgical Sciences, University of Bologna, Italy; Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.
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6
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Marrone G, Leone MS, Biolato M, Liguori A, Bianco G, Spoletini G, Gasbarrini A, Miele L, Pompili M. Therapeutic Approach to Post-Transplant Recurrence of Hepatocellular Carcinoma: Certainties and Open Issues. Cancers (Basel) 2023; 15:5593. [PMID: 38067299 PMCID: PMC10705300 DOI: 10.3390/cancers15235593] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 11/03/2023] [Accepted: 11/18/2023] [Indexed: 01/12/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is a growing indication for liver transplantation (LT). Careful candidate selection is a prerequisite to keep post-LT recurrence rates within acceptable percentages. In the pre-LT period, various types of locoregional treatments and/or systemic therapies can be used for bridging or downstaging purposes. In this context, one of the factors limiting the possibility of treatment is the degree of functional liver impairment. In the LT subject, no widely accepted indications are available to guide treatment of disease recurrence and heterogeneity exists between transplant centers. Improved liver function post LT makes multiple therapeutic strategies theoretically feasible, but patient management is complicated by the need to adjust immunosuppressive therapy and to assess potential toxicities and drug-drug interactions. Finally, there is controversy and uncertainty about the use of recently introduced immunotherapeutic drugs, mainly due to the risk of organ rejection. In this paper, we will review the most recent available literature on the management of post-transplant HCC recurrence, discussing evidence and controversies.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Maurizio Pompili
- Medical and Surgical Sciences Department, Policlinico Universitario A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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7
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van der Meeren PE, de Wilde RF, Sprengers D, IJzermans JNM. Benefit and harm of waiting time in liver transplantation for HCC. Hepatology 2023:01515467-990000000-00646. [PMID: 37972979 DOI: 10.1097/hep.0000000000000668] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 10/26/2023] [Indexed: 11/19/2023]
Abstract
Liver transplantation is the most successful treatment for limited-stage HCC. The waiting time for liver transplantation (LT) can be a critical factor affecting the oncological prognosis and outcome of patients with HCC. Efficient strategies to optimize waiting time are essential to maximize the benefits of LT and to reduce the harm of delay in transplantation. The ever-increasing demand for donor livers emphasizes the need to improve the organization of the waiting list for transplantation and to optimize organ availability for patients with and without HCC. Current progress in innovations to expand the donor pool includes the implementation of living donor LT and the use of grafts from extended donors. By expanding selection criteria, an increased number of patients are eligible for transplantation, which necessitates criteria to prevent futile transplantations. Thus, the selection criteria for LT have evolved to include not only tumor characteristics but biomarkers as well. Enhancing our understanding of HCC tumor biology through the analysis of subtypes and molecular genetics holds significant promise in advancing the personalized approach for patients. In this review, the effect of waiting time duration on outcome in patients with HCC enlisted for LT is discussed.
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Affiliation(s)
- Pam Elisabeth van der Meeren
- Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Roeland Frederik de Wilde
- Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Dave Sprengers
- Department of Gastroenterology & Hepatology, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Jan Nicolaas Maria IJzermans
- Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
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8
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Kim P, Littau M, Baker TB, Abdelsattar Z, Tonelli C, Bunn C, Kulshrestha S, Luchette FA, Scaglione S, Baker MS. The benefit of liver transplant beyond Milan criteria: An analysis using the National Cancer Database. Surgery 2022; 172:1823-1828. [PMID: 36096963 DOI: 10.1016/j.surg.2022.07.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 06/06/2022] [Accepted: 07/25/2022] [Indexed: 01/06/2023]
Abstract
BACKGROUND Published studies examining the efficacy of liver transplantation in patients presenting with hepatocellular cancer beyond the traditional Milan criteria for liver transplantation have primarily been single institution series with limited ability to compare outcomes to alternative methods of management. METHODS We queried the National Cancer Database to identify patients presenting between 2004 and 2016 with histologically confirmed clinical stage III and IVA hepatocellular cancer. Multivariable regression was used to identify factors associated with liver transplantation. Patients undergoing liver transplantation were 1:1 propensity score-matched for age, demographics, comorbid disease, clinical stage, and histologic resection margin to those undergoing surgical resection. The Kaplan-Meier method was used to compare overall survival profiles for matched cohorts. RESULTS Seven hundred and ninety-two patients met inclusion criteria-590 (74.5%) underwent surgical resection and 202 (25.5%) liver transplantation. On adjusted analysis, patients undergoing liver transplantation were less likely to have advanced age (>60 years; odds ratio 0.39, 95% confidence interval [0.21-0.71]) and to be of Black race (odds ratio 0.42, 95% confidence interval [0.23-0.73]) or Asian (odds ratio 0.25, 95% confidence interval [0.11-0.53]) ethnicity but were more likely to have advanced (Charlson score >2) comorbidity scores, (odds ratio 2.48, 95% confidence interval [1.58-3.90]) and more likely to have private health insurance (odds ratio 4.17, 95% confidence interval [1.31-18.66]) than those undergoing surgical resection. On Kaplan-Meier analysis of matched cohorts, patients undergoing liver transplantation demonstrated significantly better rates of 5-year overall survival (65.3% vs 26.3%, P < .0001) and longer median overall survival times than those undergoing resection (53.1 ± 2.78 vs 26.9 ± 1.20 months, P < .0001). CONCLUSION Liver transplantation offers the potential to be an effective treatment modality in select patients presenting with stage III and IVA hepatocellular cancer.
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Affiliation(s)
- Preston Kim
- Loyola University Chicago Stritch School of Medicine, Maywood, IL
| | - Michael Littau
- Loyola University Chicago Stritch School of Medicine, Maywood, IL
| | - Talia B Baker
- University of Chicago Pritzker School of Medicine, IL
| | - Zaid Abdelsattar
- Loyola University Chicago Stritch School of Medicine, Maywood, IL
| | - Celsa Tonelli
- Loyola University Chicago Stritch School of Medicine, Maywood, IL
| | - Corinne Bunn
- Loyola University Chicago Stritch School of Medicine, Maywood, IL
| | | | - Fred A Luchette
- Loyola University Chicago Stritch School of Medicine, Maywood, IL
| | - Steven Scaglione
- Loyola University Chicago Stritch School of Medicine, Maywood, IL
| | - Marshall S Baker
- Loyola University Chicago Stritch School of Medicine, Maywood, IL.
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9
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Kim SJ, Kim JM. Prediction models of hepatocellular carcinoma recurrence after liver transplantation: A comprehensive review. Clin Mol Hepatol 2022; 28:739-753. [PMID: 35468711 PMCID: PMC9597239 DOI: 10.3350/cmh.2022.0060] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 04/05/2022] [Accepted: 04/15/2022] [Indexed: 01/05/2023] Open
Abstract
Liver transplantation (LT) is one of the most effective treatments for hepatocellular carcinoma (HCC). Although LT eliminates HCC and greatly reduces recurrence, some patients experience recurrence after LT. Criteria and models for screening patients with a high probability of HCC recurrence after LT, starting with the Milan criteria, have been published. These models have changed over time, but a standard has not been established. We summarized HCC prediction models after LT by focusing on the application of radiologic, serologic, and pathologic factors and recent trends. This review will look at studies that are based on living donor LT and deceased donor LT, as well as studies that downstaging procedures have been performed preoperatively. This ultimately aims to help make decisions for evaluating the HCC state and selecting candidates for LT according to the circumstances of each transplantation center.
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Affiliation(s)
- Sang Jin Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
- Division of Hepatobiliopancreas and Transplant Surgery, Korea University Ansan Hospital, Republic of Korea, Ansan, Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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10
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Benkö T, König J, Theysohn JM, Schotten C, Saner FH, Treckmann J, Radunz S. Bridging treatment prior to liver transplantation for hepatocellular carcinoma: radioembolization or transarterial chemoembolization? Eur J Med Res 2022; 27:74. [PMID: 35619164 PMCID: PMC9134704 DOI: 10.1186/s40001-022-00708-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 05/16/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND In hepatocellular carcinoma (HCC) patients, intraarterial therapies are regularly employed as a bridge to liver transplantation to prevent tumor progression during waiting time. Objective of this study was to compare HCC recurrence after liver transplantation following TACE or radioembolization bridging treatment. METHODS We retrospectively analyzed prospectively collected data on 131 consecutive HCC patients who underwent liver transplantation between January 2007 and December 2017 at our liver transplant center (radioembolization n = 44, TACE n = 87). Multivariable logistic regression and cox proportional hazard regression models were used to evaluate factors associated with tumor recurrence and post-transplant survival. RESULTS Between groups, patients were comparable with regards to age and gender. In the radioembolization group, Milan criteria for HCC were met significantly less frequently (20.5% vs. 65.5%, p < 0.0001). Patients in the radioembolization group required significantly fewer intraarterial treatments (1 [1-2] vs. 1 [1-7], p = 0.0007). On explant specimen, tumor differentiation, microvascular invasion and tumor necrosis were comparable between the groups. HCC recurrence and overall survival were similar between the groups. Multivariable analysis detected increasing recipient age, male gender, complete tumor necrosis and absence of microvascular invasion being independently associated with decreased odds for HCC recurrence. Increasing model of end-stage liver disease (MELD) score and tumor recurrence were independently associated with increased odds of post-transplant death. CONCLUSIONS Intraarterial bridging treatment leading to tumor necrosis may not only prevent waitlist drop-out but also facilitate long-term successful liver transplantation in HCC patients. Both radioembolization and TACE represent potent treatment strategies.
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Affiliation(s)
- Tamás Benkö
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany
| | - Julia König
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany
| | - Jens M Theysohn
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany
| | - Clemens Schotten
- Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany
| | - Fuat H Saner
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany
| | - Jürgen Treckmann
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany
| | - Sonia Radunz
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany.
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11
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Lin X, Xiao M, Gu YJ, Zhu HK, Li MX, Zhuang L, Zheng SS, Li QY. The "No-touch" technique improves the survival of patients with advanced hepatocellular carcinomas treated by liver transplantation: A single-center prospective randomized controlled trial. Hepatobiliary Pancreat Dis Int 2022; 22:253-262. [PMID: 35568681 DOI: 10.1016/j.hbpd.2022.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 04/07/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND Liver transplantation (LT) is the best treatment for patients with hepatocellular carcinoma (HCC). However, the surgical technique needs to be improved. The present study aimed to evaluate the "no-touch" technique in LT. METHODS From January 2018 to December 2019, we performed a prospective randomized controlled trial on HCC patients who underwent LT. The patients were randomized into two groups: a no-touch technique LT group (NT group, n = 38) and a conventional LT technique group (CT group, n = 46). Operative outcomes and survival in the two groups were analyzed. RESULTS The perioperative parameters were comparable between the two groups (P > 0.05). There was no significant difference between the two groups in disease-free survival (DFS) (P = 0.732) or overall survival (OS) (P = 0.891). Of 36 patients who were beyond the Hangzhou criteria for LT, the DFS of the patients in the NT group was significantly longer than that in the CT group (median 402 vs. 126 days, P = 0.025). In 31 patients who had portal vein tumor thrombosis (PVTT), DFS and OS in the NT group were significantly better than those in the CT group (median DFS 420 vs. 167 days, P = 0.022; 2-year OS rate 93.8% vs. 66.7%, P = 0.043). In 14 patients who had diffuse-type HCCs, DFS and OS were significantly better in the NT group than in the CT group (median DFS 141 vs. 56 days, P = 0.008; 2-year OS rate 75.0% vs. 33.3%, P = 0.034). Multivariate analysis showed that for patients with PVTT and diffuse-type HCCs, the no-touch technique was an independent favorable factor for OS (PVTT: HR = 0.018, 95% CI: 0.001-0.408, P = 0.012; diffuse-type HCCs: HR = 0.034, 95% CI: 0.002-0.634, P = 0.024). CONCLUSIONS The no-touch technique improved the survival of patients with advanced HCC compared with the conventional technique. The no-touch technique may provide a new and effective LT technique for advanced HCCs.
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Affiliation(s)
- Xin Lin
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China; Zhejiang University School of Medicine, Hangzhou 310000, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China
| | - Min Xiao
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China
| | - Yang-Jun Gu
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China
| | - Heng-Kai Zhu
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China
| | - Meng-Xia Li
- Zhejiang University School of Medicine, Hangzhou 310000, China
| | - Li Zhuang
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China
| | - Shu-Sen Zheng
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China; Zhejiang University School of Medicine, Hangzhou 310000, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China
| | - Qi-Yong Li
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou 310000, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China.
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12
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Quantification of contrast agent uptake in the hepatobiliary phase helps to differentiate hepatocellular carcinoma grade. Sci Rep 2021; 11:22991. [PMID: 34837039 PMCID: PMC8626433 DOI: 10.1038/s41598-021-02499-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 11/10/2021] [Indexed: 12/02/2022] Open
Abstract
This study aimed to assess the degree of differentiation of hepatocellular carcinoma (HCC) using Gd-EOB-DTPA-assisted magnetic resonance imaging (MRI) with T1 relaxometry. Thirty-three solitary HCC lesions were included in this retrospective study. This study's inclusion criteria were preoperative Gd-EOB-DTPA-assisted MRI of the liver and a histopathological evaluation after hepatic tumor resection. T1 maps of the liver were evaluated to determine the T1 relaxation time and reduction rate between the native phase and hepatobiliary phase (HBP) in liver lesions. These findings were correlated with the histopathologically determined degree of HCC differentiation (G1, well-differentiated; G2, moderately differentiated; G3, poorly differentiated). There was no significant difference between well-differentiated (950.2 ± 140.2 ms) and moderately/poorly differentiated (1009.4 ± 202.0 ms) HCCs in the native T1 maps. After contrast medium administration, a significant difference (p ≤ 0.001) in the mean T1 relaxation time in the HBP was found between well-differentiated (555.4 ± 140.2 ms) and moderately/poorly differentiated (750.9 ± 146.4 ms) HCCs. For well-differentiated HCCs, the reduction rate in the T1 time was significantly higher at 0.40 ± 0.15 than for moderately/poorly differentiated HCCs (0.25 ± 0.07; p = 0.006). In conclusion this study suggests that the uptake of Gd-EOB-DTPA in HCCs is correlated with tumor grade. Thus, Gd-EOB-DTPA-assisted T1 relaxometry can help to further differentiation of HCC.
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13
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Pham AD, Vaz K, Ardalan ZS, Sinclair M, Apostolov R, Gardner S, Majeed A, Mishra G, Kam NM, Patwala K, Kutaiba N, Arachchi N, Bell S, Dev AT, Lubel JS, Nicoll AJ, Sood S, Kemp W, Roberts SK, Fink M, Testro AG, Angus PW, Gow PJ. Clinical outcomes of patients with two small hepatocellular carcinomas. World J Hepatol 2021; 13:1439-1449. [PMID: 34786178 PMCID: PMC8568581 DOI: 10.4254/wjh.v13.i10.1439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 06/19/2021] [Accepted: 09/02/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Management of single small hepatocellular carcinoma (HCC) is straightforward with curative outcomes achieved by locoregional therapy or resection. Liver transplantation is often considered for multiple small or single large HCC. Management of two small HCC whether presenting synchronously or sequentially is less clear. AIM To define the outcomes of patients presenting with two small HCC. METHODS Retrospective review of HCC databases from multiple institutions of patients with either two synchronous or sequential HCC ≤ 3 cm between January 2000 and March 2018. Primary outcomes were overall survival (OS) and transplant-free survival (TFS). RESULTS 104 patients were identified (male n = 89). Median age was 63 years (interquartile range 58-67.75) and the most common aetiology of liver disease was hepatitis C (40.4%). 59 (56.7%) had synchronous HCC and 45 (43.3%) had sequential. 36 patients died (34.6%) and 25 were transplanted (24.0%). 1, 3 and 5-year OS was 93.0%, 66.1% and 62.3% and 5-year post-transplant survival was 95.8%. 1, 3 and 5-year TFS was 82.1%, 45.85% and 37.8%. When synchronous and sequential groups were compared, OS (1,3 and 5 year synchronous 91.3%, 63.8%, 61.1%, sequential 95.3%, 69.5%, 64.6%, P = 0.41) was similar but TFS was higher in the sequential group (1,3 and 5 year synchronous 68.5%, 37.3% and 29.7%, sequential 93.2%, 56.6%, 48.5%, P = 0.02) though this difference did not remain during multivariate analysis. CONCLUSION TFS in patients presenting with two HCC ≤ 3 cm is poor regardless of the timing of the second tumor. All patients presenting with two small HCC should be considered for transplantation.
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Affiliation(s)
- Anh Duy Pham
- The Victorian Liver Transplant Unit, Austin Health, Heidelberg 3084, Victoria, Australia
| | - Karl Vaz
- The Victorian Liver Transplant Unit, Austin Health, Heidelberg 3084, Victoria, Australia.
| | - Zaid S Ardalan
- The Victorian Liver Transplant Unit, Austin Health, Heidelberg 3084, Victoria, Australia
| | - Marie Sinclair
- The Victorian Liver Transplant Unit, Austin Health, Heidelberg 3084, Victoria, Australia
| | - Ross Apostolov
- The Victorian Liver Transplant Unit, Austin Health, Heidelberg 3084, Victoria, Australia
| | - Sarah Gardner
- The Victorian Liver Transplant Unit, Austin Health, Heidelberg 3084, Victoria, Australia
| | - Ammar Majeed
- Department of Gastroenterology, Alfred Health, Melbourne 3000, Victoria, Australia
| | - Gauri Mishra
- Department of Gastroenterology and Hepatology, Monash Health, Clayton 3168, Victoria, Australia
| | - Ning Mao Kam
- The Victorian Liver Transplant Unit, Austin Health, Heidelberg 3084, Victoria, Australia
| | - Kurvi Patwala
- The Victorian Liver Transplant Unit, Austin Health, Heidelberg 3084, Victoria, Australia
| | - Numan Kutaiba
- Department of Radiology, Austin Health, Heidelberg 3084, Victoria, Australia
| | | | - Sally Bell
- The Melbourne Liver Group, Melbourne 3000, Victoria, Australia
| | - Anouk T Dev
- The Melbourne Liver Group, Melbourne 3000, Victoria, Australia
| | - John S Lubel
- Department of Gastroenterology, Alfred Health, Melbourne 3000, Victoria, Australia
| | - Amanda J Nicoll
- The Melbourne Liver Group, Melbourne 3000, Victoria, Australia
| | - Siddharth Sood
- The Melbourne Liver Group, Melbourne 3000, Victoria, Australia
| | - William Kemp
- Department of Gastroenterology, Alfred Health, Melbourne 3000, Victoria, Australia
| | - Stuart K Roberts
- Department of Gastroenterology, Alfred Health, Melbourne 3000, Victoria, Australia
| | - Michael Fink
- The Victorian Liver Transplant Unit, Austin Health, Heidelberg 3084, Victoria, Australia
| | - Adam G Testro
- The Victorian Liver Transplant Unit, Austin Health, Heidelberg 3084, Victoria, Australia
| | - Peter W Angus
- The Victorian Liver Transplant Unit, Austin Health, Heidelberg 3084, Victoria, Australia
| | - Paul J Gow
- The Victorian Liver Transplant Unit, Austin Health, Heidelberg 3084, Victoria, Australia
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14
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Lerut J, Foguenne M, Lai Q. Hepatocellular cancer selection systems and liver transplantation: from the tower of babel to an ideal comprehensive score. Updates Surg 2021; 73:1599-1614. [PMID: 34003479 PMCID: PMC8500859 DOI: 10.1007/s13304-021-01078-4] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 05/03/2021] [Indexed: 12/13/2022]
Abstract
The Milan criteria (MC) remain the cornerstone for the selection of patients with hepatocellular cancer (HCC) to be listed for liver transplantation (LT). Recently, several expanded criteria have been proposed to increase the transplantability of HCC patients without compromising their (oncologic) outcome. This paper aims to systematically review the different reported HCC-LT selection systems looking thereby at their ability to increase the number of transplantable patients and the overall survival and oncological outcome. A systematic review of the literature covering the period 1993 (date of the first reported HCC-LT selection system)-2021 identified 59 different inclusion criteria of HCC for LT. Among the 59 studies reporting HCC-LT selection systems, 15 (28.3%) were exclusively based on morphological aspects of the tumor; 29 (54.7%) included biologic, seven (13.2%) radiological, and two (3.8%) only included pathological tumor features. Overall, 31% more patients could be transplanted when adhering to the new HCC-LT selection systems. Despite the increased number of LT, 5-year patient and disease-free survival rates were similar between MC-IN and MC-OUT/new HCC-LT-IN criteria. A careful extension of the inclusion criteria should allow many more patients to access a potentially curative LT without compromising their outcome. The development of a widely accepted "comprehensive" HCC-LT Score able to offer a fair chance of justified transplantation to more patients should become a priority within the liver transplant community. Further studies are needed to develop internationally accepted, expanded selection criteria for liver transplantation of HCC patients.
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Affiliation(s)
- Jan Lerut
- Institute for Experimental and Clinical Research (IREC), Université Catholique de Louvain (UCL), Avenue Hippocrates 55, 1200 Brussels, Belgium
| | - Maxime Foguenne
- University Hospitals Saint-Luc Université Catholique de Louvain (UCL), Brussels, Belgium
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Rome, Italy
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15
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Pelizzaro F, Gambato M, Gringeri E, Vitale A, Cillo U, Farinati F, Burra P, Russo FP. Management of Hepatocellular Carcinoma Recurrence after Liver Transplantation. Cancers (Basel) 2021; 13:4882. [PMID: 34638365 PMCID: PMC8508053 DOI: 10.3390/cancers13194882] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/19/2021] [Accepted: 09/24/2021] [Indexed: 02/06/2023] Open
Abstract
Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), occurring in 10-15% of cases, is a major concern. A lot of work has been done in order to refine the selection of LT candidates with HCC and to improve the outcome of patients with recurrence. Despite this, the prognosis of these patients remains poor, partly due to the several areas of uncertainty in their management. Even if surveillance for HCC recurrence is crucial for early detection, there is currently no evidence to support a specific and cost-effective post-LT surveillance strategy. Concerning preventive measures, consensus on the best immunosuppressive drugs has not been reached and not enough data to support adjuvant therapy are present. Several therapeutic approaches (surgical, locoregional and systemic treatments) are available in case of recurrence, but there are still few data in the post-LT setting. Moreover, the use of immune checkpoint inhibitors is controversial in transplant recipients considered the risk of rejection. In this paper, the available evidence on the management of HCC recurrence after LT is comprehensively reviewed, considering pre- and post-transplant risk stratification, post-transplant surveillance, preventive strategies and treatment options.
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Affiliation(s)
- Filippo Pelizzaro
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
| | - Martina Gambato
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Enrico Gringeri
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Alessandro Vitale
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Fabio Farinati
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
| | - Patrizia Burra
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Francesco Paolo Russo
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
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16
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Liver Transplantation in Patients with Hepatocellular Carcinoma beyond the Milan Criteria: A Comprehensive Review. J Clin Med 2021; 10:jcm10173932. [PMID: 34501381 PMCID: PMC8432180 DOI: 10.3390/jcm10173932] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Revised: 08/22/2021] [Accepted: 08/29/2021] [Indexed: 02/07/2023] Open
Abstract
The Milan criteria (MC) were developed more than 20 years ago and are still considered the benchmark for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). However, the strict application of MC might exclude some patients who may receive a clinical benefit of LT. Several expanded criteria have been proposed. Some of these consider pretransplant morphological and biological variables of the tumor, others consider post-LT variables such as the histology of the tumor, and others combine pre- and post-LT variables. More recently, the HCC response to locoregional treatments before transplantation emerged as a surrogate marker of the biological aggressiveness of the tumor to be used as a better selection criterion for LT in patients beyond the MC at presentation. This essential review aims to present the current data on the pretransplant selection criteria for LT in patients with HCC exceeding the MC at presentation based on morphological and histological characteristics of the tumor and to critically discuss those that have been validated in clinical practice. Moreover, the role of HCC biological markers and the tumor response to downstaging procedures as new tools for selecting patients with a tumor burden outside of the MC for LT is evaluated.
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17
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Lang SA, Bednarsch J, Czigany Z, Joechle K, Kroh A, Amygdalos I, Strnad P, Bruns T, Heise D, Ulmer F, Neumann UP. Liver transplantation in malignant disease. World J Clin Oncol 2021; 12:623-645. [PMID: 34513597 PMCID: PMC8394155 DOI: 10.5306/wjco.v12.i8.623] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 06/15/2021] [Accepted: 07/23/2021] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation for malignant disease has gained increasing attention as part of transplant oncology. Following the implementation of the Milan criteria, hepatocellular carcinoma (HCC) was the first generally accepted indication for transplantation in patients with cancer. Subsequently, more liberal criteria for HCC have been developed, and research on this topic is still ongoing. The evident success of liver transplantation for HCC has led to the attempt to extend its indication to other malignancies. Regarding perihilar cholangiocarcinoma, more and more evidence supports the use of liver transplantation, especially after neoadjuvant therapy. In addition, some data also show a benefit for selected patients with very early stage intrahepatic cholangiocarcinoma. Hepatic epithelioid hemangioendothelioma is a very rare but nonetheless established indication for liver transplantation in primary liver cancer. In contrast, patients with hepatic angiosarcoma are currently not considered to be optimal candidates. In secondary liver tumors, neuroendocrine cancer liver metastases are an accepted but comparability rare indication for liver transplantation. Recently, some evidence has been published supporting the use of liver transplantation even for colorectal liver metastases. This review summarizes the current evidence for liver transplantation for primary and secondary liver cancer.
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Affiliation(s)
- Sven Arke Lang
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Jan Bednarsch
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Zoltan Czigany
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Katharina Joechle
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Andreas Kroh
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Iakovos Amygdalos
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Pavel Strnad
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Tony Bruns
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Daniel Heise
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Florian Ulmer
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Ulf Peter Neumann
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
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18
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Ma KW, Chan ACY, Chok KSH, She WH, Cheung TT, Dai WC, Fung JYY, Lo CM. Liver transplantation: would it be the best and last chance of cure for hepatocellular carcinoma with major venous invasion? Hepatobiliary Surg Nutr 2021; 10:308-314. [PMID: 34159158 PMCID: PMC8188125 DOI: 10.21037/hbsn.2020.03.09] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Accepted: 10/15/2019] [Indexed: 01/11/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT) signifies advanced disease, whether LT confers any survival superiority over resection remains uncertain. METHODS A propensity score matched (PSM) analysis of liver transplantation (LT) and liver resection (LR) for HCC with PVTT was performed. RESULTS A consecutive series of 88 patients who received either LT (10 DDLTs and 3 LDLTs) or LR (n=75) respectively were recruited. Before PSM, the LT group has a higher MELD score (17.3 vs. 7.8, P<0.001), lower serum AFP levels (96 vs. 2,164 ng/mL, P=0.017) and smaller tumour size (4 vs. 10 cm, P<0.001). The 5-year overall survival for LT and LR were 55.4% and 15.9% respectively (P=0.007). After matching for serum AFP levels and tumour size, 1-, 3- and 5-year overall survival for LT were 81 ng/mL, 3.9 cm, 80%, 70% and 70% and the corresponding rates for LR were 1,417 ng/mL, 5.3 cm, 51.8%, 19,6% and 9.8% (P value =0.12, 0.27 and 0.009 respectively). CONCLUSIONS LT is associated with significantly better oncological outcomes in HCC patients with PVTT involving the lobar or segmental level. A modest expansion of selection criteria to include small HCC with segmental PVTT should be considered.
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Affiliation(s)
- Ka Wing Ma
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | | | | | - Wong Hoi She
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Tan To Cheung
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Wing Chiu Dai
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | | | - Chung Mau Lo
- Department of Surgery, The University of Hong Kong, Hong Kong, China
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19
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Jiang G, Ling S, Zhan Q, Zhuang L, Xu X. Downstaging treatment for patients with hepatocelluar carcinoma before transplantation. Transplant Rev (Orlando) 2021; 35:100606. [PMID: 33636480 DOI: 10.1016/j.trre.2021.100606] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 01/30/2021] [Accepted: 01/31/2021] [Indexed: 12/13/2022]
Abstract
Liver transplantation (LT), one of the radical methods of treating liver cancer, has brought new hope for the treatment of unresectable liver cancer. Currently, patients who meet transplant criteria can achieve a favorable prognosis, but those who exceed transplant criteria tend not to have very satisfactory outcomes. For patients whose tumor burden exceeds the transplant criteria, downstaging treatment is a promising method to reduce tumor burden to within the transplant criteria that may lead to good posttransplant survival. Multiple treatments, such as transcatheter arterial chemoembolization (TACE), transarterial radioembolization (TARE), percutaneous ethanol injection (PEI), and radiofrequency ablation (RFA), have been used as downstaging treatments. However, there are still some issues that limit the effectiveness of downstaging treatments, such as the inclusion criteria for downstaging, which the choice of downstaging treatment method, and the endpoint of downstaging, all of which are worthy of further discussion. Based on the published literature, this review discusses these issues.
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Affiliation(s)
- Guangjiang Jiang
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
| | - Sunbin Ling
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
| | - Qifan Zhan
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
| | - Li Zhuang
- Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310003, China.
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China.
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20
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Finotti M, Vitale A, Volk M, Cillo U. A 2020 update on liver transplant for hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2020; 14:885-900. [PMID: 32662680 DOI: 10.1080/17474124.2020.1791704] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Accepted: 07/01/2020] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Hepatocellular carcinoma is the most frequent liver tumor and is associated with chronic liver disease in 90% of cases. In selected cases, liver transplantation represents an effective therapy with excellent overall survival. AREA COVERED Since the introduction of Milan criteria in 1996, numerous alternative selection systems to LT for HCC patients have been proposed. Debate remains about how best to select HCC patients for transplant and how to prioritize them on the waiting list. EXPERT OPINION The selection of the best scoring system to propose in the context of LT for HCC is far to be identified. In this review, we analyze and categorize the various selection systems, assessing their roles in the different decisional phases.
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Affiliation(s)
- Michele Finotti
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, Padova University Hospital , Padova, Italy
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, Padova University Hospital , Padova, Italy
| | - Michael Volk
- Division of Gastroenterology and Hepatology, Loma Linda University Health , Loma Linda, California, USA
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, Padova University Hospital , Padova, Italy
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Ju MR, Yopp AC. Evolving thresholds for liver transplantation in hepatocellular carcinoma: A Western experience. Ann Gastroenterol Surg 2020; 4:208-215. [PMID: 32490334 PMCID: PMC7240148 DOI: 10.1002/ags3.12316] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Revised: 01/09/2020] [Accepted: 01/16/2020] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Once considered an experimental treatment with dismal survival rates, liver transplantation for HCC entered a new era with the establishment of the Milan criteria over 20 years ago. In the modern post-Milan-criteria era, 5-year survival outcomes are now upwards of 70% in select patients. Liver transplantation (LT) is now considered the optimal treatment for patients with moderate to severe cirrhosis and HCC, and the rates of transplantation in the United States are continuing to rise. Several expanded selection criteria have been proposed for determining which patients with HCC should be candidates for undergoing LT with similar overall and recurrence-free survival rates to patients within the Milan criteria. There is also a growing experience with downstaging of patients who fall outside conventional LT criteria at the time of HCC diagnosis with the goal of tumor shrinkage via locoregional therapies to become a candidate for transplantation. The aim of this review article is to characterize the various patient selection criteria for LT, discuss balancing organ stewardship with outcome measures in HCC patients, present evidence on the role of downstaging for large tumors, and explore future directions of LT for HCC.
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Affiliation(s)
- Michelle R. Ju
- Division of Surgical OncologyDepartment of SurgeryUniversity of Texas Southwestern Medical CenterDallasTexas
| | - Adam C. Yopp
- Division of Surgical OncologyDepartment of SurgeryUniversity of Texas Southwestern Medical CenterDallasTexas
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Ling LLL, Hsu CC, Yong CC, Elsarawy AM, Chan YC, Wang CC, Li WF, Lin TL, Kuo FY, Cheng YF, Lin LM, Chen CL, Lin CC. FDG-PET predicted unfavorable tumor histology in living donor liver transplant recipients; a retrospective cohort study. Int J Surg 2019; 69:124-131. [DOI: 10.1016/j.ijsu.2019.07.035] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 07/26/2019] [Accepted: 07/26/2019] [Indexed: 02/07/2023]
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Recent advances in liver transplantation for cancer: The future of transplant oncology. JHEP Rep 2019; 1:377-391. [PMID: 32039389 PMCID: PMC7005652 DOI: 10.1016/j.jhepr.2019.07.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 07/15/2019] [Accepted: 07/16/2019] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation is widely indicated as a curative treatment for selected patients with hepatocellular carcinoma. However, with recent therapeutic advances, as well as efforts to increase the donor pool, liver transplantation has been carefully expanded to patients with other primary or secondary malignancies in the liver. Cholangiocarcinoma, colorectal and neuroendocrine liver metastases, and hepatic epithelioid haemangioendothelioma are amongst the most relevant new indications. In this review we discuss the fundamental concepts of this ambitious undertaking, as well as the newest indications for liver transplantation, with a special focus on future perspectives within the recently established concept of transplant oncology.
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A Point-based Histologic Scoring System for Hepatocellular Carcinoma Can Stratify Risk of Posttransplant Tumor Recurrence. Am J Surg Pathol 2019; 42:855-865. [PMID: 29649017 DOI: 10.1097/pas.0000000000001053] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Eligibility for liver transplant is most commonly decided by measuring tumor size and number on radiographic imaging. However, this method often underestimates the extent of disease. Evaluation of tumor histology has been shown to improve risk stratification when compared with imaging-based transplant criteria, but the World Health Organization (WHO) guidelines for grading hepatocellular carcinoma (HCC) are imprecise and require subjective interpretation by the pathologist. We performed a retrospective analysis of 190 explanted livers containing HCC and correlated histologic features with posttransplant recurrence to formulate a three-tiered, point-based scoring system that categorizes tumors as having a low, intermediate, or high risk of recurrence. Our Recurrence Risk Assessment Score (RRAS) evaluates tumor architecture and specific cytologic features-nuclear pleomorphism, cytoplasmic amphophilia, and nuclear-to-cytoplasmic ratio-showing superior stratification of HCC recurrence risk compared with imaging criteria and grade assigned by WHO methodology. Stratifying tumors using RRAS criteria, the rate of recurrence after transplant was 0% among low-risk tumors (compared with 3% of well-differentiated tumors), 12% among intermediate-risk tumors (compared with 15% of moderately differentiated tumors), and 54% among high-risk tumors (compared with 29% of poorly differentiated tumors). Receiver operating characteristic analysis shows significantly improved performance of RRAS criteria in predicting HCC recurrence compared with WHO grade (area under curve of 0.841 and 0.671, respectively; P=0.0061). Our results indicate that evaluation of tumor histology offers superior prediction of recurrence risk following liver transplantation compared with radiographic criteria, and that the RRAS system better stratifies recurrence risk compared with HCC grading by WHO methodology.
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Forner A, Da Fonseca LG, Díaz-González Á, Sanduzzi-Zamparelli M, Reig M, Bruix J. Controversies in the management of hepatocellular carcinoma. JHEP Rep 2019; 1:17-29. [PMID: 32039350 PMCID: PMC7001551 DOI: 10.1016/j.jhepr.2019.02.003] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 01/11/2019] [Accepted: 01/13/2019] [Indexed: 02/07/2023] Open
Abstract
The management of hepatocellular carcinoma (HCC) has evolved considerably over the last decade. Surveillance of cirrhotic patients and refinements to imaging techniques have enabled a relevant proportion of patients to be diagnosed at an early stage, when effective therapies are feasible. Resection, transplantation and ablation are all options in patients with early stage HCC. Thus, there is some controversy regarding which is the best treatment approach in challenging scenarios. There have also been major developments in locoregional therapies, particularly in intra-arterial approaches. Finally, the systemic treatment for HCC has changed dramatically following the demonstration of a survival benefit with sorafenib; there are currently several first-line (sorafenib and lenvatinib) and second-line (regorafenib, cabozantinib and ramucirumab) treatments that have shown a survival benefit. Expectations for immune checkpoint inhibitors are high, with the results of the ongoing phase III trials eagerly awaited. In this review we discuss some of the controversies in the management of HCC, focussing in particular on systemic therapy.
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Affiliation(s)
- Alejandro Forner
- Barcelona Clinic Liver Cancer (BCLC) group, Liver Unit, Hospital Clínic of Barcelona, Fundació Clínic per a la Recerca Biomédica (FCRB), IDIBAPS, University of Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
| | - Leonardo G Da Fonseca
- Barcelona Clinic Liver Cancer (BCLC) group, Liver Unit, Hospital Clínic of Barcelona, Fundació Clínic per a la Recerca Biomédica (FCRB), IDIBAPS, University of Barcelona, Spain
| | - Álvaro Díaz-González
- Barcelona Clinic Liver Cancer (BCLC) group, Liver Unit, Hospital Clínic of Barcelona, Fundació Clínic per a la Recerca Biomédica (FCRB), IDIBAPS, University of Barcelona, Spain
| | - Marco Sanduzzi-Zamparelli
- Barcelona Clinic Liver Cancer (BCLC) group, Liver Unit, Hospital Clínic of Barcelona, Fundació Clínic per a la Recerca Biomédica (FCRB), IDIBAPS, University of Barcelona, Spain
| | - María Reig
- Barcelona Clinic Liver Cancer (BCLC) group, Liver Unit, Hospital Clínic of Barcelona, Fundació Clínic per a la Recerca Biomédica (FCRB), IDIBAPS, University of Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer (BCLC) group, Liver Unit, Hospital Clínic of Barcelona, Fundació Clínic per a la Recerca Biomédica (FCRB), IDIBAPS, University of Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
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Pagano D, Barbera F, Conaldi PG, Seidita A, Di Francesco F, Di Carlo D, Bàrbara M, Tuzzolino F, Luca A, Gruttadauria S. Role of Allelic Imbalance in Predicting Hepatocellular Carcinoma (HCC) Recurrence Risk After Liver Transplant. Ann Transplant 2019; 24:223-233. [PMID: 31015392 PMCID: PMC6500106 DOI: 10.12659/aot.913692] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background One of the most controversial problems for liver transplantation in patients affected by hepatocellular carcinoma (HCC) remains the lack of an oncologic staging system to predict cancer recurrence after liver transplantation (LT). We analyzed allelic imbalance (AI) in 19 microsatellites, and assessed the post-LT HCC recurrence risk. Material/Methods Seventy-one patients were included; 18 had tumor recurrence within 5 years post-transplant. Molecular analysis was done in the primary HCC and peripheral blood samples: a total of 19 microsatellites was used to assess AI. Specific AI was evaluated when outside of range value between 0.66 and 1.5. Based on data in the literature, we grouped the 19 microsatellites into 4 panels. We calculated the fractional allelic imbalance (FAI) to make comparisons between different panels including different subsets of microsatellites. Results We report that AI was associated with HCC recurrence in 3 main loci (D3S2303, D9S251, and D9S254). Tumor recurrence was associated only with 2 specific panels with 9 microsatellites previously reported to be associated with high risk for HCC recurrence. Our data show that fractional allelic imbalance (FAI) index has good negative ability to predict HCC recurrence (Panel 2: negative predictive value of 95%). Conclusions AI analysis could have prognostic value in risk management of HCC recurrence after LT, especially for early recurrence.
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Affiliation(s)
- Duilio Pagano
- Department for Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Mediterranean Institute for Transplantation and High Specialization Therapies (IRCCS-ISMETT), Palermo, Italy
| | - Floriana Barbera
- Department of Laboratory Medicine and Advanced Biotechnologies, Mediterranean Institute for Transplantation and High Specialization Therapies (IRCCS-ISMETT), Palermo, Italy
| | - Pier Giulio Conaldi
- Department of Laboratory Medicine and Advanced Biotechnologies, Mediterranean Institute for Transplantation and High Specialization Therapies (IRCCS-ISMETT), Palermo, Italy.,Ri.MED Foundation, Palermo, Italy
| | - Aurelio Seidita
- Department for Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Mediterranean Institute for Transplantation and High Specialization Therapies (IRCCS-ISMETT), Palermo, Italy
| | - Fabrizio Di Francesco
- Department for Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Mediterranean Institute for Transplantation and High Specialization Therapies (IRCCS-ISMETT), Palermo, Italy
| | - Daniele Di Carlo
- Department for Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Mediterranean Institute for Transplantation and High Specialization Therapies (IRCCS-ISMETT), Palermo, Italy
| | - Marco Bàrbara
- Department for Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Mediterranean Institute for Transplantation and High Specialization Therapies (IRCCS-ISMETT), Palermo, Italy
| | - Fabio Tuzzolino
- Research Office, Mediterranean Institute for Transplantation and High Specialization Therapies (IRCCS-ISMETT), Palermo, Italy
| | - Angelo Luca
- Department of Diagnostic and Therapeutic Services, Mediterranean Institute for Transplantation and High Specialization Therapies (IRCCS-ISMETT), Palermo, Italy
| | - Salvatore Gruttadauria
- Department for Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Mediterranean Institute for Transplantation and High Specialization Therapies (IRCCS-ISMETT), Palermo, Italy
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Citores MJ, Lucena JL, de la Fuente S, Cuervas-Mons V. Serum biomarkers and risk of hepatocellular carcinoma recurrence after liver transplantation. World J Hepatol 2019; 11:50-64. [PMID: 30705718 PMCID: PMC6354126 DOI: 10.4254/wjh.v11.i1.50] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 11/13/2018] [Accepted: 12/05/2018] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma (HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to 85%of 3- to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, des-gamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, can predict the risk for HCC recurrence after transplantation. These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral recurrence after LT.
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Affiliation(s)
- Maria J Citores
- Department of Internal Medicine, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Majadahonda 28222, Spain.
| | - Jose L Lucena
- Liver Transplantation Unit, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda 28222, Spain
| | - Sara de la Fuente
- Department of Internal Medicine, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda 28222, Spain
| | - Valentin Cuervas-Mons
- Department of Internal Medicine, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda 28222, Spain
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Patterns of Discordance Between Pretransplant Imaging Stage of Hepatocellular Carcinoma and Posttransplant Pathologic Stage: A Contemporary Appraisal of the Milan Criteria. Transplantation 2018; 102:648-655. [PMID: 29319629 DOI: 10.1097/tp.0000000000002056] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Patients with hepatocellular carcinoma (HCC) exceeding Milan criteria on explant pathology are at increased risk of recurrence and death. Discordance between contemporary magnetic resonance imaging (MRI) and explant pathology, and preoperative characteristics predictive of discordance are not well understood. METHODS Patients who underwent orthotopic liver transplantation for HCC after preoperative MRI were identified in a prospectively collected institutional database (January 2003 to December 2013). Patients were dichotomized to "within" or "outside" Milan criteria by both imaging and explant pathologic evaluation. Binary logistic regression and Kaplan-Meier methodology were used to identify independent predictors of imaging/pathologic discordance and its impact on posttransplant survival. RESULTS Of 318 patients with HCC meeting Milan criteria by MRI at the time of orthotopic liver transplantation, 248 (78.0%) remained within a pathological correlate of Milan criteria on explant examination. Understaging was associated with worse median recurrence-free survival (64.0 months vs 140.0 months, P = 0.002) and overall survival (96.0 months vs 143.0 months, P = 0.005), and did not vary between patients exceeding criteria due to tumor explant greater than 5 cm, more than 3 tumor foci, or a tumor greater than 3 cm in the setting of multifocality. Discordance was independently associated with an increasing serum alpha fetal protein level (odds ratio, 2.82; 95% confidence interval, 1.37-5.79; P = 0.005). CONCLUSIONS Underestimating HCC burden before liver transplant remains frequent despite contemporary imaging technologies. Patients with an increasing alpha fetal protein before transplantation may benefit from more frequent testing or novel neoadjuvant therapies.
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Yaprak O, Acar S, Ertugrul G, Dayangac M. Role of pre-transplant 18F-FDG PET/CT in predicting hepatocellular carcinoma recurrence after liver transplantation. World J Gastrointest Oncol 2018; 10:336-343. [PMID: 30364796 PMCID: PMC6198297 DOI: 10.4251/wjgo.v10.i10.336] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Revised: 05/27/2018] [Accepted: 06/14/2018] [Indexed: 02/05/2023] Open
Abstract
The last two decades have seen a paradigm shift in the selection of patients with hepatocellular carcinoma (HCC) for liver transplantation. Microvascular invasion and differentiation have been the most significant factors affecting post-transplant recurrence; however, because of inherent disadvantages of pre-transplant biopsy, histological criteria never gained popularity. Recently, the selection criteria evolved from morphological to biological criteria, such as biomarkers and response to loco-regional therapy. With the introduction of multimodality imaging, combination of computed tomography with nuclear medicine imaging, particularly, 18F-fluorodeoxyglucose positron emission tomography fulfilled an unmet need and rapidly became a critical component of HCC management. This review article will focus on the use of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography in the pre-transplant evaluation of HCC patients with special discussion on its ability to predict HCC recurrence after liver transplantation.
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Affiliation(s)
- Onur Yaprak
- Medipol University Hospital, Center for Organ Transplantation, Istanbul 34214, Turkey
| | - Sencan Acar
- Atasehir Memorial Hospital, Center for Organ Transplantation, Istanbul 34758, Turkey
| | - Gokhan Ertugrul
- Medipol University Hospital, Center for Organ Transplantation, Istanbul 34214, Turkey
| | - Murat Dayangac
- Medipol University Hospital, Center for Organ Transplantation, Istanbul 34214, Turkey
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Park J, Choi GS, Gwak MS, Ko JS, Han S, Han B, Joh JW, Kim SJ, Lee SK, Kwon CD, Kim J, Cho CW, Kim GS. Intraoperative abortion of adult living donor liver transplantation: 15 cases from 1,179 cases in 20 years of experience in a single center. Ann Surg Treat Res 2018; 95:213-221. [PMID: 30310804 PMCID: PMC6172354 DOI: 10.4174/astr.2018.95.4.213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Revised: 04/10/2018] [Accepted: 05/07/2018] [Indexed: 11/30/2022] Open
Abstract
Purpose This study aimed to report intraoperative abortion of adult living donor liver transplantation (LDLT). Methods From June 1997 to December 2016, 1,179 adult LDLT cases were performed. 15 cases (1.3%) of intraoperative abortions in LDLT were described. Results Among 15 cases, 5 intraoperative abortions were donor-related, and remaining 10 cases were recipient-related. All donor-related abortions were due to unexpected steatohepatitis. Among remaining 10 recipient-related intraoperative abortions, unexpected extension of hepatocellular carcinoma was related in 5 cases. Two cases of intraoperative abortions were related to bowel inflammation, and 2 cases were associated with severe adhesion related to previous treatment. One recipient with severe pulmonary hypertension was also aborted. Conclusion Complete prevention of aborted LDLT is still not feasible. In this regard, further efforts to minimize intraoperative abortion are required.
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Affiliation(s)
- Jungchan Park
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gyu-Seong Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Mi Sook Gwak
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Justin Sangwook Ko
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sangbin Han
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Bobae Han
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sung Joo Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Suk-Koo Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Choonhyuck David Kwon
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chan Woo Cho
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gaab Soo Kim
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Rastogi A. Changing role of histopathology in the diagnosis and management of hepatocellular carcinoma. World J Gastroenterol 2018; 24:4000-4013. [PMID: 30254404 PMCID: PMC6148422 DOI: 10.3748/wjg.v24.i35.4000] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 07/23/2018] [Accepted: 08/01/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common and fatal cancer in the world. HCC frequently presents with advanced disease, has a high recurrence rate and limited treatment options, which leads to very poor prognosis. This warrants urgent improvement in the diagnosis and treatment. Liver biopsy plays very important role in the diagnosis and prognosis of HCC, but with technical advancements and progression in the field of imaging, clinical guidelines have restricted the role of biopsy to very limited situations. Biopsy also has its own problems of needle tract seeding of tumor, small risk of complications, technical and sampling errors along with interpretative errors. Despite this, tissue analysis is often required because imaging is not always specific, limited expertise and lack of advanced imaging in many centers and limitations of imaging in the diagnosis of small, mixed and other variant forms of HCC. In addition, biopsy confirmation is often required for clinical trials of new drugs and targeted therapies. Tissue biomarkers along with certain morphological features, phenotypes and immune-phenotypes that serve as important prognostic and outcome predictors and as decisive factors for therapy decisions, add to the continuing role of histopathology. Advancements in cancer biology and development of molecular classification of HCC with clinic pathological correlation, lead to discovery of HCC phenotypic surrogates of prognostic and therapeutically significant molecular signatures. Thus tissue characteristics and morphology based correlates of molecular subtypes provide invaluable information for management and prognosis. This review thus focuses on the importance of histopathology and resurgence of role of biopsy in the diagnosis, management and prognostication of HCC.
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Affiliation(s)
- Archana Rastogi
- Department of Pathology, Institute of Liver & Biliary Sciences, New Delhi 110070, India
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32
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Lai Q, Vitale A. Transplantation for hepatocellular cancer: pushing to the limits? Transl Gastroenterol Hepatol 2018; 3:61. [PMID: 30363754 PMCID: PMC6182031 DOI: 10.21037/tgh.2018.09.07] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Accepted: 09/04/2018] [Indexed: 12/12/2022] Open
Abstract
Milan criteria (MC) represents the cornerstone in the selection of patients with hepatocellular cancer (HCC) waiting for liver transplantation (LT). MC represent the precursor of the scores based on the idea of "utility": in other terms, the scoring systems typically used in the field of LT oncology present the exclusive aim of selecting the cases with the best post-LT outcomes. However, some other scores have been proposed specifically investigating the risk of death or tumour progression during the waiting list. In this case, the selection process is connected with the idea of "priority": patients at higher risk for drop-out (DO) should be selected, prioritising them or, conversely, deciding to de-list them due to the high risk of post-LT futile transplant. Lastly, models based on the concept of "benefit", namely the balancing between priority and utility, have been recently created. The present review aims to examine these three different types of scoring systems, trying to underline their pro and cons in the allocation process of HCC patients.
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Affiliation(s)
- Quirino Lai
- General Surgery and Organ Transplantation Unit, Department of Surgery, Sapienza University of Rome, Rome, Italy
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, Padua University, Padua, Italy
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Lee HA, Cho EY, Kim TH, Lee Y, Suh SJ, Jung YK, Kim JH, An H, Seo YS, Kim DS, Yim HJ, Yeon JE, Byun KS, Um SH. Risk Factors for Dropout From the Liver Transplant Waiting List of Hepatocellular Carcinoma Patients Under Locoregional Treatment. Transplant Proc 2018; 50:3521-3526. [PMID: 30577230 DOI: 10.1016/j.transproceed.2018.08.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2018] [Accepted: 08/29/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND In new organ allocation policy, patients with hepatocellular carcinoma (HCC) experience a 6-month delay in being granted Model for End-Stage Liver Disease exception points. However, it may not be fair for patients at risk of early progression of HCC. METHODS All patients who were diagnosed as United Network for Organ Sharing (UNOS) stage 1 or 2 of HCC between January 2004 and December 2012 were included. Patients who received surgical resection or liver transplant (LT) as a primary treatment and who did not receive any treatment for HCC were excluded. Patients with baseline Model for End-Stage Liver Disease score ≥22 were also excluded because they have a higher chance of receiving LT. Patients who developed extrahepatic progression within 1 year were considered as high-risk for early recurrence after LT. RESULTS A total of 586 patients were included. Mean (SD) age was 59.9 (10.3) years and 409 patients (69.8%) were men. The cumulative incidence of estimated dropout was 8.9% at 6 months; size of the maximum nodule (≥3 cm) and nonachievement of complete response were independent factors. Extrahepatic progression developed in 16 patients (2.7%) within 1 year; size of the maximum nodule (4 cm) and alpha-fetoprotein level (>100 ng/mL) were independent predictors. CONCLUSIONS The estimated dropout rate from the waiting list within 6 months was 8.9%. Advantage points might be needed for patients with maximum nodule size ≥3 cm or those with noncomplete response. However, in patients with maximum nodule size ≥4 cm or alpha-fetoprotein level >100 ng/mL, caution is needed.
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Affiliation(s)
- H A Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - E Y Cho
- Department of Biostatistics, Korea University College of Medicine, Seoul, Korea
| | - T H Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Y Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - S J Suh
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Y K Jung
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - J H Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - H An
- Department of Biostatistics, Korea University College of Medicine, Seoul, Korea
| | - Y S Seo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
| | - D-S Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - H J Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
| | - J E Yeon
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - K S Byun
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - S H Um
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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Shen J, Liu J, Li C, Wen T, Yan L, Yang J. The Impact of Tumor Differentiation on the Prognosis of HBV-Associated Solitary Hepatocellular Carcinoma Following Hepatectomy: A Propensity Score Matching Analysis. Dig Dis Sci 2018; 63:1962-1969. [PMID: 29736828 DOI: 10.1007/s10620-018-5077-5] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Accepted: 04/16/2018] [Indexed: 02/05/2023]
Abstract
AIM The role of tumor differentiation in the prognosis of hepatocellular carcinoma (HCC) after hepatectomy remains controversial. The present study aimed to classify the impact of tumor differentiation on solitary hepatitis B viral (HBV)-associated HCC using propensity score matching analysis. METHODS Between January 2009 and March 2015, the data of 721 HCC patients in West China Hospital were prospectively collected and analyzed. Propensity matching analysis was applied to overcome the imbalance in baseline characteristics. Survival analysis was performed using the Kaplan-Meier method. Risk factors were identified by the Cox proportional hazards model. RESULTS All HCC patients were classified into the moderately well-differentiated HCCs group (group A, n = 442, 61.3%) or poorly differentiated HCCs group (group B, n = 279, 38.7%). Patients with poorly differentiated HCCs commonly had a larger tumor size, more advanced tumors, and a higher alpha-fetoprotein (AFP) level. Patients with poorly differentiated HCCs had a poorer recurrence-free survival and overall survival before and after propensity score matching analysis. Poorly differentiated tumors, positive serum hepatitis B viral e antigen, positive hepatitis B virus deoxyribonucleic acid load, tumor size, microvascular invasion, and AFP > 400 ng/ml were risk factors of a poor outcome. CONCLUSIONS Our propensity model provided strong evidence that a poorly differentiated tumor had a negative impact on the recurrence and long-term survival of solitary HBV-associated HCCs after curative hepatectomy. Antiviral therapy might improve their prognosis.
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Affiliation(s)
- Junyi Shen
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Jiaye Liu
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Chuan Li
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Tianfu Wen
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
| | - Lvnan Yan
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Jiayin Yang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
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Park IK, Yu JS, Cho ES, Kim JH, Chung JJ. Apparent diffusion coefficient of hepatocellular carcinoma on diffusion-weighted imaging: Histopathologic tumor grade versus arterial vascularity during dynamic magnetic resonance imaging. PLoS One 2018; 13:e0197070. [PMID: 29750794 PMCID: PMC5947906 DOI: 10.1371/journal.pone.0197070] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2017] [Accepted: 03/13/2018] [Indexed: 12/16/2022] Open
Abstract
Objectives Apparent diffusion coefficient (ADC) has been suggested to reflect the tumor grades of hepatocellular carcinomas (HCCs); i.e., it can be used as a biomarker to predict the patients’ prognosis. To verify its feasibility as a biomarker, the present study sought to determine how the ADC values of HCC are affected by a tumor’s histopathologic grade and arterial vascularity. Materials and methods From 131 consecutive patients, 141 surgically resected HCCs (16 well-differentiated [wd-HCCs], 83 moderately-differentiated [md-HCCs], and 42 poorly-differentiated HCCs [pd-HCCs]) were subjected to a comparison of the tumors’ arterial vascularity (non-, slightly-, or markedly-hypervascular) determined on dynamic magnetic resonance imaging (MRI) and the ADC was measured retrospectively. Results The pd-HCCs (1.05±0.16 × 10−3 mm2/s) had a significantly lower ADC than md-HCCs (1.16±0.21 × 10−3 mm2/s; p = 0.010), but there was no significant difference compared to wd-HCCs (1.11±0.18 × 10−3 mm2/s; p = 0.968). The mean ADC was significantly higher in markedly hypervascular lesions (1.20±0.20 × 10−3 mm2/s) than in nonhypervascular lesions (0.95±0.14 × 10−3mm2/s; p<0.001) or slightly hypervascular lesions (1.04±0.15 × 10−3mm2/s; p<0.001). The ADC values and arterial vascularity were significantly correlated in wd-HCCs (p = 0.005) and md-HCCs (p<0.001). The mean ADC of pd-HCCs was significantly lower than those of other lesions, even in the markedly hypervascular lesion subgroup (p = 0.020). Conclusion Although pd-HCC constantly shows low ADCs regardless of arterial vascularities, ADCs cannot stably stratify histopathologic tumor grades due to the variable features of wd-HCCs; and the ADC should be used with caution as a tumor biomarker of HCC.
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Affiliation(s)
- In Kyung Park
- Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Gangnam-Gu, Seoul, Korea
| | - Jeong-Sik Yu
- Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Gangnam-Gu, Seoul, Korea
- * E-mail:
| | - Eun-Suk Cho
- Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Gangnam-Gu, Seoul, Korea
| | - Joo Hee Kim
- Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Gangnam-Gu, Seoul, Korea
| | - Jae-Joon Chung
- Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Gangnam-Gu, Seoul, Korea
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Vitale A, Lai Q, Farinati F, Bucci L, Giannini EG, Napoli L, Ciccarese F, Rapaccini GL, Di Marco M, Caturelli E, Zoli M, Borzio F, Sacco R, Cabibbo G, Virdone R, Marra F, Felder M, Morisco F, Benvegnù L, Gasbarrini A, Svegliati-Baroni G, Foschi FG, Missale G, Masotto A, Nardone G, Colecchia A, Bernardi M, Trevisani F, Pawlik TM. Utility of Tumor Burden Score to Stratify Prognosis of Patients with Hepatocellular Cancer: Results of 4759 Cases from ITA.LI.CA Study Group. J Gastrointest Surg 2018; 22:859-871. [PMID: 29352441 DOI: 10.1007/s11605-018-3688-y] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Accepted: 01/08/2018] [Indexed: 01/31/2023]
Abstract
BACKGROUND Dichotomous models like Milan Criteria represent the routinely used tools for predicting the outcome of patients with hepatocellular carcinoma (HCC). However, a paradigm shift from a dichotomous to continuous prognostic stratification should represent a good strategy for improving the prediction process. Recently, the tumor burden score (TBS) has been proposed for selecting patients with colorectal liver metastases. To date, TBS has not been validated in a large HCC population. The main objective of this study was to evaluate the prognostic power of TBS in an HCC population treated with different curative and palliative modalities. METHODS Prospectively collected data from consecutive HCC patients managed in 24 institutions participating in the ITA.LI.CA group between Jan 2002 and Mar 2015 were analyzed (n = 4759). A sub-analysis focused on 3909 patients with the radiological evidence of vascular invasion or metastatic disease was also performed. RESULTS TBS demonstrated the best discriminative ability when compared to MC and other tumor-specific scores. At multivariable Cox regression analysis, TBS was an independent risk factor of overall survival, with a 6% increased risk for patient death for each point increase in TBS. At survival analysis, when TBS ≥ 8 was connected with MELD ≥ 15 and alpha-fetoprotein ≥ 1000 ng/mL, patients presenting all these three risk factors presented the worst results (p value < 0.0001). CONCLUSIONS Survival prediction of HCC patients was very well done using TBS model, even stratifying the population in relation to the presence of metastases and/or vascular invasion. TBS model was the best in terms of discriminatory ability and goodness of fit when compared with other continuous or binary variables. Its incorporation in a model composed by tumor- and liver function-related variables further increases its survival prediction.
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Affiliation(s)
- Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Quirino Lai
- Liver Transplant and Hepatobiliary Surgery Unit, Sapienza University of Rome, UmbertoI Policlinic of Rome, Viale delPoliclinico 155, 00161, Rome, Italy.
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Laura Bucci
- Department of Medical and Surgical Sciences, Division of Semeiotics, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Policlinico San Martino, Genoa, Italy
| | - Lucia Napoli
- Department of Medical and Surgical Sciences, Division of Internal Medicine, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | | | - Gian Lodovico Rapaccini
- Division of Internal Medicine and Gastroenterology, Complesso Integrato Columbus, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Maria Di Marco
- Division of Medicine, Bolognini Hospital, Seriate, Italy
| | | | - Marco Zoli
- Department of Medical and Surgical Sciences, Division of Internal Medicine, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Franco Borzio
- Department of Medicine, Division of Radiology, Fatebenefratelli Hospital, Milan, Italy
| | - Rodolfo Sacco
- Division of Gastroenterology and Metabolic Diseases, University Hospital of Pisa, Pisa, Italy
| | - Giuseppe Cabibbo
- Biomedical Department of Internal and Specialistic Medicine, Division of Gastroenterology, University of Palermo, Palermo, Italy
| | - Roberto Virdone
- Division of Internal Medicine 2, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
| | - Fabio Marra
- Internal Medicine and Hepatology, Department of Experimental and Clinical Medicine, University of Firenze, Florence, Italy
| | - Martina Felder
- Division of Gastroenterology, Bolzano Regional Hospital, Bolzano, Italy
| | - Filomena Morisco
- Department of Medicine and Surgery, Division of Gastroenterology, University of Naples, "Federico II", Naples, Italy
| | - Luisa Benvegnù
- Department of Molecular Medicine, University of Padua, Padua, Italy
| | - Antonio Gasbarrini
- Division of Internal Medicine and Gastroenterology, Policlinico Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy
| | | | | | - Gabriele Missale
- Division of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Alberto Masotto
- Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, University of Naples "Federico II", Naples, Italy
| | - Antonio Colecchia
- Department of Surgical and Medical sciences, Gastroenterology Unit, Alma Mater Studiorum-Università of Bologna, Bologna, Italy
| | - Mauro Bernardi
- Department of Medical and Surgical Sciences, Division of Semeiotics, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Franco Trevisani
- Department of Medical and Surgical Sciences, Division of Semeiotics, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Timothy M Pawlik
- Department of Surgery, Wexner Medical Center at The Ohio State University, Columbus, OH, USA
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Chen K, Guo H, Zheng S. Improved performance of Hangzhou criteria for liver transplantation of hepatocellular carcinoma: the role of liver resident FoxP3 + regulatory T cells. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2018; 11:1328-1337. [PMID: 31938228 PMCID: PMC6958165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 12/23/2017] [Accepted: 01/16/2018] [Indexed: 06/10/2023]
Abstract
Tumor-infiltrating lymphocytes (TILs) represent the host immune response to a tumor. In this study, we investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) in liver transplant candidates with hepatocellular carcinoma (HCC) and established an improved prognostic model for predicting clinical outcome. CD3+, CD4+, CD8+, and FoxP3+ TILs were assessed by immunohistochemistry in tumor tissue from 153 patients who had undergone liver transplantation for HCC. Prognostic effects of these TIL subsets and other clinicopathologic factors were evaluated by Kaplan-Meier and Cox regression analysis. The area under the curve (AUC) and net reclassification improvement (NRI) were calculated to determine if the new model improved risk prediction. We found that the prevalence of intra-tumoral FoxP3+ Tregs among CD4+ TILs, but not the density of intra-tumoral FoxP3+ Tregs, was an independent predictor for disease-free (DFS) and overall survival (OS) (P<0.05). A Cox model combining the prevalence of intra-tumoral FoxP3+ Tregs with Hangzhou criteria was highly predictive of tumor recurrence and death. The AUCs of the Cox model for recurrence (0.733; 95% CI, 0.656-0.802) and survival (0.765; 95% CI, 0.690-0.830) were significantly increased when compared with those of Hangzhou criteria (P<0.001). Net reclassification improvement showed that predictability of the Cox models for both recurrence and survival was superior to Hangzhou criteria (P<0.05). Our results collectively showed that the prevalence of intra-tumoral FoxP3+ Tregs is a promising prognostic predictor for HCC patients after OLT. Inclusion of FoxP3+ Tregs into Hangzhou criteria could improveme risk prediction.
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Affiliation(s)
- Kangjie Chen
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, China
| | - Haijun Guo
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, China
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Santambrogio R, Cigala C, Barabino M, Maggioni M, Scifo G, Bruno S, Bertolini E, Opocher E, Bulfamante G. Intraoperative ultrasound for prediction of hepatocellular carcinoma biological behaviour: Prospective comparison with pathology. Liver Int 2018; 38:312-320. [PMID: 28732141 DOI: 10.1111/liv.13524] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2017] [Accepted: 07/13/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Preoperative prediction of both microinvasive hepatocellular carcinoma and histological grade of hepatocellular carcinoma is pivotal to treatment planning and prognostication. The aim of this study was to evaluate whether some intraoperative ultrasound features correlate with both the presence of same histological patterns and differentiation grade of hepatocellular carcinoma on the histological features of the primary resected tumour. METHODS All patients with single, small hepatocellular carcinoma that underwent hepatic resection were included in this prospective double-blind study: the intraoperative ultrasound patterns of nodule were registered and compared with similar histological features. RESULTS A total of 179 patients were enclosed in this study: 97 (54%) patients (34% in HCC ≤2 cm) had a microinvasive hepatocellular carcinoma at ultrasound examination, while 82 (46%) patients (41% in HCC ≤2 cm) at histological evaluation. Statistical analysis showed that diameters ≤2 cm, presence of satellites and microinvasive hepatocellular carcinoma at ultrasound examination were the variables with the strongest association with the histological findings. In the multivariate analysis, the vascular microinfiltration and infiltrative hepatocellular carcinoma aspect were independent predictors for grading. CONCLUSIONS In patients with cirrhosis and hepatocellular carcinoma, the prevalence of microinvasive hepatocellular carcinoma is high, even in cases of HCC ≤2 cm. Intraoperative ultrasound findings strongly correlated with histopathological criteria in detecting microinvasive patterns and are useful to predict neoplastic differentiation. The knowledge of these features prior to treatment are highly desired (this can be obtained by an intraoperative ultrasound examination), as they could help in providing optimal management of patients with hepatocellular carcinoma.
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Affiliation(s)
- Roberto Santambrogio
- UOC di Chirurgia Epato-bilio-pancreatica e Digestiva, ASST Santi Paolo e Carlo, Università di Milano, Milano, Italy
| | - Claudia Cigala
- U.O.C. Anatomia Patologica, ASST Santi Paolo e Carlo, Università di Milano, Milano, Italy
| | - Matteo Barabino
- UOC di Chirurgia Epato-bilio-pancreatica e Digestiva, ASST Santi Paolo e Carlo, Università di Milano, Milano, Italy
| | - Marco Maggioni
- U.O.C. Anatomia Patologica, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università di Milano, Milano, Italy
| | - Giovanna Scifo
- UOC di Chirurgia Epato-bilio-pancreatica e Digestiva, ASST Santi Paolo e Carlo, Università di Milano, Milano, Italy
| | - Savino Bruno
- Humanitas University Medicine and Humanitas Research Hospital, Rozzano, Milano, Italy
| | - Emanuela Bertolini
- Cattedra di Medicina Interna, Azienda Ospedaliera San Paolo - Dipartimento di Medicina, Chirurgia ed Odontoiatria, Università degli Studi di Milano, Milan, Italy
| | - Enrico Opocher
- UOC di Chirurgia Epato-bilio-pancreatica e Digestiva, ASST Santi Paolo e Carlo, Università di Milano, Milano, Italy
| | - Gaetano Bulfamante
- U.O.C. Anatomia Patologica, ASST Santi Paolo e Carlo, Università di Milano, Milano, Italy
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Pfiffer TEF, Seehofer D, Nicolaou A, Neuhaus R, Riess H, Trappe RU. Recurrent hepatocellular carcinoma in liver transplant recipients: Parameters affecting time to recurrence, treatment options and survival in the sorafenib era. TUMORI JOURNAL 2018; 97:436-41. [DOI: 10.1177/030089161109700404] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Background A growing number of patients with hepatocellular carcinoma undergo liver transplantation, but there is little data on recurrence and its treatment in the posttransplant setting. Methods This article presents a retrospective analysis of adult hepatocellular carcinoma patients. The aim of the study was to characterize the clinical pattern of posttransplant hepatocellular carcinoma recurrence, treatment options in recurrence and overall survival after liver transplantation and after recurrence. Results A total of 139 patients with histological proven hepatocellular carcinoma was included in the study. The median follow-up after liver transplantation was 37.2 months. Twenty-four of 139 patients experienced a recurrence. In 72.7% of the cases, the hepatocellular carcinoma recurred outside the transplant. Median overall survival after recurrence was 23.1 months. A total of 68.2% of patients received a mean of 2.2 treatments for posttransplant hepatocellular carcinoma recurrence. While on treatment with sorafenib, the use of mTOR inhibitors and radiotherapy had no statistically significant effect on overall survival, complete surgical resection of metastatic lesions significantly improved overall survival. Non-resectable patients with isolated hepatic relapse also benefited from local control strategies. Conclusions Posttransplant hepatocellular carcinoma recurrence frequently is located outside the transplant, and despite the proven efficacy of sorafenib, complete surgical resection of metastatic lesions remains the hallmark of treatment.
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Affiliation(s)
- Tulio EF Pfiffer
- Department of Hematology, Oncology and Tumor Immunology, Campus Virchow-Klinikum, Berlin, Germany
| | - Daniel Seehofer
- Department of General, Visceral and Transplantation Surgery, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - Annett Nicolaou
- Department of Hematology, Oncology and Tumor Immunology, Campus Virchow-Klinikum, Berlin, Germany
| | - Ruth Neuhaus
- Department of General, Visceral and Transplantation Surgery, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - Hanno Riess
- Department of Hematology, Oncology and Tumor Immunology, Campus Virchow-Klinikum, Berlin, Germany
| | - Ralf U Trappe
- Department of Hematology, Oncology and Tumor Immunology, Campus Virchow-Klinikum, Berlin, Germany
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Benzoni E, Lorenzin D, Favero A, Adani G, Baccarani U, Molaro R, Zompicchiatti A, Saccomano E, Avellini C, Bresadola F, Uzzau A. Liver Resection for Hepatocellular Carcinoma: a Multivariate Analysis of Factors Associated with Improved Prognosis. the Role of Clinical, Pathological and Surgical Related Factors. TUMORI JOURNAL 2018; 93:264-8. [PMID: 17679461 DOI: 10.1177/030089160709300306] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Aims and background Hepatocellular carcinoma (Hcc) is the third most common cause of cancer death. The aim of this study is to examine the factors associated with improved prognosis in Hcc after liver resection. Patients and methods From September 1989 to March 2005, 134 consecutive patients had liver resection for Hcc on cirrhosis at our department. We performed 54 major liver resections and 80 limited resections. All patients enrolled in the study were followed-up three times during the first year after resection and twice the next years. Results In-hospital mortality rate was 7.4%, about 50% of these cases were Child-Pugh B patients. Morbidity rate was 47.7%, caused by the rising of ascites, temporary liver impairment function, biliary fistula, hepatic abscess, hemoperitoneum and pleural effusion. Overall survival resulted to be influenced by etiology (P = 0.03), underlying liver disease, in particular Child A vs BC (P = 0.04), Endmondson-Steiner grading (P = 0.01), the absence of a capsule (P = 0.004), the presence of more than one lesion (P = 0.02), lesion's size over 5 cm (P = 0.04), Pringle maneuver length over than 20 minutes (P = 0.03), an amount of resected liver volume lesser than 50% of total liver volume (P = 0. 03), and the relapse of Hcc (P = 0.01). Conclusions The treatment of hepatocellular carcinoma should be both the most radical to obtain the best outcome and to reduce the recurrence's rate, and the most suitable according to the patient's condition, lesion's characteristics and underlying liver disease: because of the large number of factors affecting the outcome of Hcc, unfortunately, we are still far from an agreement upon a group of criteria useful to select the best candidates for liver resection.
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Affiliation(s)
- Enrico Benzoni
- Department of Surgery, School of Medicine, University of Udine, Udine, Italy.
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Tunissiolli NM, Castanhole-Nunes MMU, Pavarino ÉC, da Silva RF, da Silva RDCMA, Goloni-Bertollo EM. Clinical, Epidemiological and Histopathological Aspects in Patients with Hepatocellular Carcinoma Undergoing Liver Transplantation. Asian Pac J Cancer Prev 2018; 19. [PMID: 30360608 PMCID: PMC6291045 DOI: 10.22034/apjcp.2018.19.10.2795] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background: Hepatocellular Carcinoma (HCC) is the primary liver cancer with high incidence and mortality rates.
Currently one of the major etiologies for liver disease, HCC and liver transplantation is nonalcoholic fatty liver disease
(NAFLD). The aim of the present study was to evaluate the epidemiological, histopathological and clinical aspects of
HCC transplant patients, with emphasis on NAFLD etiology. Methods: This study included all HCC patients submitted
to liver transplantation from 2010 to 2016 of the University Reference Center. The analyzed variables were age, gender,
ethnicity, causes that led to liver transplantation, alpha-fetoprotein (AFP) dosage, histological aspects, recurrence,
survival and NAFLD. Results: A total of 60 patients were included in the study being 80% men with a mean age of
58.3 ± 10.6 years. All patients were cirrhotic. The causes that led to the transplantation were the presence of the hepatitis
C virus (HCV) (56.6% of the patients), an association of the virus with alcohol (20%), the presence of the hepatitis B
virus (HBV) (20%), alcoholic liver disease (ALD) (50.9%) and NAFLD (25%). Of the latter, eight were diagnosed
pre-transplantation and seven were NAFLD carriers without a previous diagnosis. Regarding the Edmondson-Steiner
histological classification, 58.5% of the patients were classified as grade ≤ II. Conclusions: There is predominance of
male patients with a mean age of 58.3 years. Degree ≤ II is the most frequent to the Edmondson-Steiner histological
classification in the evaluated casuistic. HCV, ALD and NAFLD is the most common etiological agents found in the
study. The (high) underestimated prevalence of NAFLD in the pre-transplanted patients is due to the fact that all patients
presented cirrhosis, masking NAFLD signals.
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Affiliation(s)
| | | | | | - Renato Ferreira da Silva
- Department of Surgery and Liver Transplantation, Hospital de Base/FUNFARME, Sao Jose do Rio Preto Medical School (FAMERP), Sao Jose do Rio Preto, Brazil
| | - Rita de Cássia Martins Alves da Silva
- Department of Surgery and Liver Transplantation, Hospital de Base/FUNFARME, Sao Jose do Rio Preto Medical School (FAMERP), Sao Jose do Rio Preto, Brazil
| | - Eny Maria Goloni-Bertollo
- Research Unit of Genetics and Molecular Biology (UPGEM), Sao Jose do Rio Preto, Brazil,For Correspondence:
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Huang LF, Wan P, Xu DW, Jeong S, Feng MX, Zhang JJ, Xia Q. Nomogram predicting pulmonary metastasis of hepatocellular carcinoma after liver transplantation. Oncotarget 2017; 9:2425-2434. [PMID: 29416782 PMCID: PMC5788650 DOI: 10.18632/oncotarget.23418] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Accepted: 09/21/2017] [Indexed: 12/12/2022] Open
Abstract
A novel prognostic nomogram predicting post-transplant pulmonary metastasis was established with a primary cohort of 308 HCC patients who received liver transplantation between 2007 and 2011 at Ren Ji Hospital. The C-indexes for predicting pulmonary metastasis was 0.85. The calibration curves fitted well between the predicted and actual outcomes. The decision curve analysis indicated that our nomogram was the optimal decision-making strategy for PM prediction compared to Milan, University of California San Franscisco, and up-to-seven criteria. These results were further validated by data from 103 patients who underwent liver transplantation between 2011 and 2012 at the same institution. In conclusion, our nomogram could be used as an effective tool to predict PM after liver transplantation.
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Affiliation(s)
- Li-Feng Huang
- Department of Hepatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Ping Wan
- Department of Hepatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Dong-Wei Xu
- Department of Hepatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Seogsong Jeong
- Department of Hepatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Ming-Xuan Feng
- Department of Hepatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Jian-Jun Zhang
- Department of Hepatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Qiang Xia
- Department of Hepatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
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Uchiyama H, Itoh S, Yoshizumi T, Ikegami T, Harimoto N, Soejima Y, Harada N, Morita K, Toshima T, Motomura T, Maehara Y. Living donor liver transplantation for hepatocellular carcinoma: results of prospective patient selection by Kyushu University Criteria in 7 years. HPB (Oxford) 2017; 19:1082-1090. [PMID: 28888776 DOI: 10.1016/j.hpb.2017.08.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2017] [Revised: 08/02/2017] [Accepted: 08/12/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Expanding patient selection beyond the Milan criteria in living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC) has long been a matter for debate. We have used the Kyushu University Criteria - maximum tumor diameter <5 cm or des-γ-carboxy prothrombin <300 mAU/ml - in LDLT for HCC since June 2007. The aim of the present study was to present the results of our prospective patient selection by Kyushu University Criteria and to confirm whether or not our criteria were justified. METHODS The entire study period was divided into the pre-Kyushu era (July 1999-May 2007) and the Kyushu era (June 2007-November 2014). Eighty-nine and 90 patients underwent LDLT for HCC in the pre-Kyushu era and the Kyushu era, respectively. RESULTS In the pre-Kyushu era, there were significant differences in recurrence-free and disease-specific survival between the beyond-Milan and the within-Milan patients. In the Kyushu era, however, the differences in recurrence-free and disease-specific survival between the beyond-Milan and the within-Milan patients disappeared. The 5-year overall patient survival in the Kyushu era was 89.4%. CONCLUSION Our selection criteria enabled a considerable number of beyond-Milan patients to undergo LDLT without jeopardizing the recurrence-free, and disease-specific, and overall patient survival.
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Affiliation(s)
- Hideaki Uchiyama
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan.
| | - Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Toru Ikegami
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Norifumi Harimoto
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Yuji Soejima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Noboru Harada
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Kazutoyo Morita
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Takeo Toshima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Takashi Motomura
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Yoshihiko Maehara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan
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Rosenblatt RE, Tafesh ZH, Halazun KJ. Role of inflammatory markers as hepatocellular cancer selection tool in the setting of liver transplantation. Transl Gastroenterol Hepatol 2017; 2:95. [PMID: 29264433 DOI: 10.21037/tgh.2017.10.04] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Accepted: 10/17/2017] [Indexed: 12/12/2022] Open
Abstract
Since the advent of the Milan criteria in 1996 and its widespread adoption for selection of patients with hepatocellular carcinoma (HCC) who would benefit from transplant, there has been an extensive hunt for the ideal clinical biomarker to predict HCC recurrence. This is because Milan lack does not include tumor biology indices and recurrence rates remain in the 15-20% range worldwide. While a 'silver-bullet' biomarker has not been found, several useful inflammatory markers have been identified and used in scoring systems that supersede Milan in their ability to predict HCC recurrence post liver transplantation (LT). In this review, we aim to summarize the role of inflammatory markers paly in the selection of HCC patients awaiting LT.
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Affiliation(s)
- Russell E Rosenblatt
- Division of gastroenterology and hepatology, Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY, USA
| | - Zaid H Tafesh
- Division of gastroenterology and hepatology, Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY, USA
| | - Karim J Halazun
- Department of surgery, Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY, USA
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Zanetto A, Shalaby S, Vitale A, Mescoli C, Ferrarese A, Gambato M, Franceschet E, Germani G, Senzolo M, Romano A, Angeli P, Rugge M, Farinati F, Forton DM, Cillo U, Burra P, Russo FP. Dropout rate from the liver transplant waiting list because of hepatocellular carcinoma progression in hepatitis C virus-infected patients treated with direct-acting antivirals. Liver Transpl 2017; 23:1103-1112. [PMID: 28544587 DOI: 10.1002/lt.24790] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Revised: 05/08/2017] [Accepted: 05/13/2017] [Indexed: 12/13/2022]
Abstract
Concerns about an increased hepatocellular carcinoma (HCC) recurrence rate following direct-acting antiviral (DAA) therapy in patients with cirrhosis with a prior complete oncological response have been raised. Data regarding the impact of HCV treatment with DAAs on wait-list dropout rates in patients with active HCC and HCV-related cirrhosis awaiting liver transplantation (LT) are lacking. HCV-HCC patients listed for LT between January 2015 and May 2016 at Padua Liver Transplant Center were considered eligible for the study. After enrollment, patients were divided into 2 groups, depending on whether they underwent DAA treatment while awaiting LT or not. For each patient clinical, serological, and virological data were collected. HCC characteristics were radiologically evaluated at baseline and during follow-up (FU). For transplanted patients, pathological assessment of the explants was performed and recurrence rates were calculated. A total of 23 patients treated with DAAs and 23 controls were enrolled. HCC characteristics at time of LT listing were comparable between the 2 groups. Median FU was 10 and 7 months, respectively, during which 2/23 (8.7%) and 1/23 (4.3%) dropout events due to HCC progression were registered (P = 0.90). No significant differences in terms of radiological progression were highlighted (P = 0.16). A total of 9 out of 23 (39%) patients and 14 out of 23 (61%) controls underwent LT, and histopathological analysis showed no differences in terms of median number and total tumor volume of HCC nodules, tumor differentiation, or microvascular invasion. During post-LT FU, 1/8 (12.5%) DAA-treated patient and 1/12 (8.3%) control patient experienced HCC recurrence (P = 0.60). In conclusion, viral eradication does not seem to be associated with an increased risk of dropout due to neoplastic progression in HCV-HCC patients awaiting LT. Liver Transplantation 23 1103-1112 2017 AASLD.
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Affiliation(s)
- Alberto Zanetto
- Gastroenterology/Multivisceral Transplant Unit, Padua, Italy
| | - Sarah Shalaby
- Gastroenterology/Multivisceral Transplant Unit, Padua, Italy
| | - Alessandro Vitale
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, Padua, Italy
| | | | | | - Martina Gambato
- Gastroenterology/Multivisceral Transplant Unit, Padua, Italy
| | | | - Giacomo Germani
- Gastroenterology/Multivisceral Transplant Unit, Padua, Italy
| | - Marco Senzolo
- Gastroenterology/Multivisceral Transplant Unit, Padua, Italy
| | - Antonietta Romano
- Unit of Internal Medicine and Hepatology, Department of Medicine, Padua University Hospital, Padua, Italy
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology, Department of Medicine, Padua University Hospital, Padua, Italy
| | - Massimo Rugge
- Surgical Pathology and Cytopathology Unit, Padua, Italy
| | | | - Daniel M Forton
- Department of Gastroenterology and Hepatology, St. George's University Hospitals National Health Service Foundation Trust, London, United Kingdom
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, Padua, Italy
| | - Patrizia Burra
- Gastroenterology/Multivisceral Transplant Unit, Padua, Italy
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Wang L, Liu Y, Li W, Song Z. Growth differentiation factor 15 promotes cell viability, invasion, migration, and angiogenesis in human liver carcinoma cell line HepG2. Clin Res Hepatol Gastroenterol 2017; 41:408-414. [PMID: 28161428 DOI: 10.1016/j.clinre.2016.12.009] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Revised: 12/02/2016] [Accepted: 12/07/2016] [Indexed: 02/04/2023]
Abstract
AIM This study was aimed to explore the role of growth differentiation factor 15 (GDF15) in hepatocellular carcinoma (HCC). METHODS Human liver carcinoma cell line HepG2 was used and transfected with vector and/or short hairpin RNA (shRNA) against GDF15. Then, the transfection efficiency was ascertained by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Cell viability was measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyltetrazolium bromide (MTT). Cell invasion and migration were measured by Transwell assay and Scratch assay. In addition, human umbilical vein endothelial cell (HUVEC) tube formation assay was performed to analysis the angiogenesis. Further, the protein expressions of epithelial-mesenchymal transition (EMT)-related factors were measured by Western blot. RESULT We found that GDF15 overexpression significantly facilitated cell viability, cell invasion, migration, and angiogenesis (P<0.05 or P<0.01). The protein expressions of N-Cadherin, Vimentin and Twist1 were up-regulated by GDF15 overexpression, while E-Cadherin was down-regulated. Reciprocally, using a GDF15-shRNA strategy, we observed that GDF15 downregulation inhibited both basal and GDF15-induced cell viability, migration, invasion and angiogenesis in HepG2 cells. CONCLUSION GDF15 could promote cell viability, invasion, migration, and angiogenesis of HepG2 cells. GDF15 overexpression might be a potential risk factor of HCC.
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Affiliation(s)
- Liang Wang
- The Second Department of General Surgery, Cangzhou Central Hospital, No. 16 Xinhua West Road, 061000 Cangzhou, Hebei, China.
| | - Yagang Liu
- The Second Department of General Surgery, Cangzhou Central Hospital, No. 16 Xinhua West Road, 061000 Cangzhou, Hebei, China
| | - Wei Li
- The Second Department of General Surgery, Cangzhou Central Hospital, No. 16 Xinhua West Road, 061000 Cangzhou, Hebei, China
| | - Zhe Song
- The Second Department of General Surgery, Cangzhou Central Hospital, No. 16 Xinhua West Road, 061000 Cangzhou, Hebei, China
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shen JY, Li C, Wen TF, Yan LN, Li B, Wang WT, Yang JY, Xu MQ, wen J. Transplantation versus hepatectomy for HCC beyond the Milan criteria: A propensity score analysis. Int J Surg 2017; 44:33-42. [DOI: 10.1016/j.ijsu.2017.05.034] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Revised: 05/01/2017] [Accepted: 05/15/2017] [Indexed: 01/27/2023]
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Cascales-Campos PA, Romero PR, Schneider MA, Lopez-Lopez V, Navarro JL, Frutos L, Pons Miñano JA, Paricio PP. Positron emission tomography/computed tomography in patients with hepatocellular carcinoma undergoing liver transplantation. Useful, necessary or irrelevant? Eur J Radiol 2017. [DOI: 10.1016/j.ejrad.2017.03.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Park MS, Lee KW, Kim H, Choi Y, Hong G, Yi NJ, Suh KS. Primary Living-donor Liver Transplantation Is Not the Optimal Treatment Choice in Patients With Early Hepatocellular Carcinoma With Poor Tumor Biology. Transplant Proc 2017; 49:1103-1108. [DOI: 10.1016/j.transproceed.2017.03.016] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Biolato M, Marrone G, Miele L, Gasbarrini A, Grieco A. Liver transplantation for intermediate hepatocellular carcinoma: An adaptive approach. World J Gastroenterol 2017; 23:3195-3204. [PMID: 28566879 PMCID: PMC5434425 DOI: 10.3748/wjg.v23.i18.3195] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Revised: 03/12/2017] [Accepted: 04/12/2017] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma is becoming an increasing indication for liver transplantation, but selection and allocation of patients are challenging because of organ shortages. Conventional Milan criteria are the reference for the selection of patients worldwide, but many expanded criteria, like University of California San Francisco criteria and up-to-7 criteria, have demonstrated that survival and recurrence results are lower than those for restricted indications. Correct staging is crucial and should include surrogate markers of biological aggressiveness (α-fetoprotein, response to loco-regional treatments). Successful down-staging can select between patients with tumor burden initially beyond transplantation criteria those with a more favorable biology, provided a 3-mo stability in meeting the transplantation criteria. Allocation rules are constantly adjusted to minimize the imbalance between the priorities of candidates with and without hepatocellular carcinoma, and take into account local donor rate and waitlist dynamics. Recently, Mazzaferro et al proposed a benefit-oriented "adaptive approach", in which the selection and allocation of patients are based on their response to non-transplantation treatments: low priority for transplantation in case of complete response, high priority in case of partial response or recurrence, and no listing in case of progression beyond transplantation criteria.
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