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Andrade R, Perez-Rojas J, da Silva SG, Miskinyte M, Quaresma MC, Frazão LP, Peixoto C, Cubells A, Montalvá EM, Figueiredo A, Cipriano A, Gonçalves-Reis M, Proença D, Folgado A, Pereira-Leal JB, Oliveira RC, Pinto-Marques H, Tralhão JG, Berenguer M, Cardoso J. HepatoPredict Accurately Selects Hepatocellular Carcinoma Patients for Liver Transplantation Regardless of Tumor Heterogeneity. Cancers (Basel) 2025; 17:500. [PMID: 39941867 PMCID: PMC11816190 DOI: 10.3390/cancers17030500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/13/2025] [Accepted: 01/19/2025] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND/OBJECTIVES Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths rising worldwide. This is leading to an increased demand for liver transplantation (LT), the most effective treatment for HCC in its initial stages. However, current patient selection criteria are limited in predicting recurrence and raise ethical concerns about equitable access to care. This study aims to enhance patient selection by refining the HepatoPredict (HP) tool, a machine learning-based model that combines molecular and clinical data to forecast LT outcomes. METHODS The updated HP algorithm was trained on a two-center dataset and assessed against standard clinical criteria. Its prognostic performance was evaluated through accuracy metrics, with additional analyses considering tumor heterogeneity and potential sampling bias. RESULTS HP outperformed all clinical criteria, particularly regarding negative predictive value, addressing critical limitations in existing selection strategies. It also demonstrated improved differentiation of recurrence-free and overall survival outcomes. Importantly, the prognostic accuracy of HP remained largely unaffected by intra-nodule and intra-patient heterogeneity, indicating its robustness even when biopsies were taken from smaller or non-dominant nodules. CONCLUSIONS These findings support the usage of HP as a valuable tool for optimizing LT candidate selection, promoting fair organ allocation and enhancing patient outcomes through integrated analysis of molecular and clinical data.
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Affiliation(s)
- Rita Andrade
- Surgery Department, Centro Hospitalar e Universitário de Coimbra, 3004-561 Coimbra, Portugal; (R.A.); (J.G.T.)
- Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal;
| | - Judith Perez-Rojas
- Pathology Service, Hospital Universitari i Politècnic La Fe, 46026 Valencia, Spain;
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain; (A.C.); (E.M.M.); (M.B.)
- Instituto de Investigación Sanitaria La Fe (ISS La Fe), 46026 Valencia, Spain
| | - Sílvia Gomes da Silva
- Hepato-Biliary-Pancreatic and Transplantation Centre, Hospital Curry Cabral, Unidade Local de Saúde de São José, 1069-166 Lisbon, Portugal; (S.G.d.S.)
- NOVA Medical School, 1169-056 Lisbon, Portugal
| | - Migla Miskinyte
- Ophiomics Precision Medicine, 1600-514 Lisbon, Portugal; (M.M.); (M.C.Q.); (L.P.F.); (C.P.); (M.G.-R.); (D.P.); (A.F.); (J.B.P.-L.)
| | - Margarida C. Quaresma
- Ophiomics Precision Medicine, 1600-514 Lisbon, Portugal; (M.M.); (M.C.Q.); (L.P.F.); (C.P.); (M.G.-R.); (D.P.); (A.F.); (J.B.P.-L.)
| | - Laura P. Frazão
- Ophiomics Precision Medicine, 1600-514 Lisbon, Portugal; (M.M.); (M.C.Q.); (L.P.F.); (C.P.); (M.G.-R.); (D.P.); (A.F.); (J.B.P.-L.)
| | - Carolina Peixoto
- Ophiomics Precision Medicine, 1600-514 Lisbon, Portugal; (M.M.); (M.C.Q.); (L.P.F.); (C.P.); (M.G.-R.); (D.P.); (A.F.); (J.B.P.-L.)
| | - Almudena Cubells
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain; (A.C.); (E.M.M.); (M.B.)
- Instituto de Investigación Sanitaria La Fe (ISS La Fe), 46026 Valencia, Spain
- Hepatology Unit, Hospital Universitari i Politècnic La Fe, 46026 Valencia, Spain
| | - Eva M. Montalvá
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain; (A.C.); (E.M.M.); (M.B.)
- Instituto de Investigación Sanitaria La Fe (ISS La Fe), 46026 Valencia, Spain
- Liver Transplantation and Surgery Unit, Hospital Universitari I Politècnic La Fe, 46026 Valencia, Spain
- Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain
| | - António Figueiredo
- Pathology Service, Hospital Curry Cabral, Unidade Local de Saúde de São José, 1069-166 Lisbon, Portugal;
| | - Augusta Cipriano
- Pathology Department, Unidade Local de Saúde de Coimbra, 3004-561 Coimbra, Portugal;
| | - Maria Gonçalves-Reis
- Ophiomics Precision Medicine, 1600-514 Lisbon, Portugal; (M.M.); (M.C.Q.); (L.P.F.); (C.P.); (M.G.-R.); (D.P.); (A.F.); (J.B.P.-L.)
| | - Daniela Proença
- Ophiomics Precision Medicine, 1600-514 Lisbon, Portugal; (M.M.); (M.C.Q.); (L.P.F.); (C.P.); (M.G.-R.); (D.P.); (A.F.); (J.B.P.-L.)
| | - André Folgado
- Ophiomics Precision Medicine, 1600-514 Lisbon, Portugal; (M.M.); (M.C.Q.); (L.P.F.); (C.P.); (M.G.-R.); (D.P.); (A.F.); (J.B.P.-L.)
| | - José B. Pereira-Leal
- Ophiomics Precision Medicine, 1600-514 Lisbon, Portugal; (M.M.); (M.C.Q.); (L.P.F.); (C.P.); (M.G.-R.); (D.P.); (A.F.); (J.B.P.-L.)
| | - Rui Caetano Oliveira
- Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal;
- Pathology Department, Unidade Local de Saúde de Coimbra, 3004-561 Coimbra, Portugal;
- Coimbra Institute for Clinical and Biomedical Research (iCBR), 3000-548 Coimbra, Portugal
- Centro de Investigação em Meio Ambiente, Genética e Oncobiologia (CIMAGO), 3001-301 Coimbra, Portugal
- Centro Académico e Clínico (CAC), 3004-531 Coimbra, Portugal
| | - Hugo Pinto-Marques
- Hepato-Biliary-Pancreatic and Transplantation Centre, Hospital Curry Cabral, Unidade Local de Saúde de São José, 1069-166 Lisbon, Portugal; (S.G.d.S.)
- NOVA Medical School, 1169-056 Lisbon, Portugal
| | - José Guilherme Tralhão
- Surgery Department, Centro Hospitalar e Universitário de Coimbra, 3004-561 Coimbra, Portugal; (R.A.); (J.G.T.)
- Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal;
- Coimbra Institute for Clinical and Biomedical Research (iCBR), 3000-548 Coimbra, Portugal
- Centro de Investigação em Meio Ambiente, Genética e Oncobiologia (CIMAGO), 3001-301 Coimbra, Portugal
- Centro Académico e Clínico (CAC), 3004-531 Coimbra, Portugal
| | - Marina Berenguer
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain; (A.C.); (E.M.M.); (M.B.)
- Instituto de Investigación Sanitaria La Fe (ISS La Fe), 46026 Valencia, Spain
- Hepatology Unit, Hospital Universitari i Politècnic La Fe, 46026 Valencia, Spain
- Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain
| | - Joana Cardoso
- Ophiomics Precision Medicine, 1600-514 Lisbon, Portugal; (M.M.); (M.C.Q.); (L.P.F.); (C.P.); (M.G.-R.); (D.P.); (A.F.); (J.B.P.-L.)
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Bredin P, Galvin Z, O'Kane GM. Role of immunotherapy in managing cancers prior to liver transplantation. Curr Opin Organ Transplant 2025; 30:3-11. [PMID: 39620576 DOI: 10.1097/mot.0000000000001187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2024]
Abstract
PURPOSE OF REVIEW Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape in advanced hepatocellular carcinoma and increasingly are being evaluated in earlier stage disease. Herein we explore the role of ICIs pre-liver transplant for liver cancers. RECENT FINDINGS Given the high response rates with combination approaches including locoregional treatments, more patients with liver confined disease, without vascular invasion, who have received ICIs are now being rendered eligible for potential liver transplant. This opportunity to expand the population who may benefit from liver transplant has also come with challenges recognizing the global shortage of organs. Post-liver transplant immunosuppression potentially competes with the immune-stimulating effects of ICIs and graft rejection has been a concern. ICIs may provide an opportunity to maintain patients on the waiting list but an understanding of who is likely to benefit is needed, to circumvent possible toxicities. In addition, ICIs are now considered standard of care, in combination with chemotherapy, for advanced cholangiocarcinoma, where the role of liver transplant is evolving. SUMMARY As the eligibility criteria globally for liver transplant in the setting of malignancy continues to expand, the integration of ICIs becomes increasingly important.
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Affiliation(s)
| | - Zita Galvin
- St Vincent's University Hospital, Elm Park
- University College Dublin, Ireland
| | - Grainne M O'Kane
- St Vincent's University Hospital, Elm Park
- University College Dublin, Ireland
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Gundavda KK, Patkar S, Varty GP, Shah N, Velmurugan K, Goel M. Liver Resection for Hepatocellular Carcinoma: Recent Advances. J Clin Exp Hepatol 2025; 15:102401. [PMID: 39286759 PMCID: PMC11402310 DOI: 10.1016/j.jceh.2024.102401] [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: 03/28/2024] [Accepted: 08/06/2024] [Indexed: 09/19/2024] Open
Abstract
Hepatocellular carcinoma (HCC) represents a significant global health burden. Surgery remains a cornerstone in the curative treatment of HCC, and recent years have witnessed notable advancements aimed at refining surgical techniques and improving patient outcomes. This review presents a detailed examination of the recent innovations in HCC surgery, highlighting key developments in both surgical approaches and adjunctive therapies. Advanced imaging technologies have revolutionized preoperative assessment, enabling precise tumour localization and delineation of vascular anatomy. The use of three-dimensional rendering has significantly augmented surgical planning, facilitating more accurate and margin-free resections. The advent of laparoscopic and robotic-assisted surgical techniques has ushered in an era of minimal access surgery, offering patients the benefits of shorter hospital stays and faster recovery times, while enabling equivalent oncological outcomes. Intraoperative innovations such as intraoperative ultrasound (IOUS) and fluorescence-guided surgery have emerged as valuable adjuncts, allowing real-time assessment of tumour extent and aiding in parenchyma preservation. The integration of multimodal therapies, including neoadjuvant and adjuvant strategies, has allowed for 'bio-selection' and shown the potential to optimize patient outcomes. With the advent of augmented reality and artificial intelligence (AI), the future holds immense potential and may represent significant strides towards optimizing patient outcomes and refining the standard of care.
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Affiliation(s)
- Kaival K Gundavda
- Department of Gastrointestinal and Hepatobiliary Surgery, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Shraddha Patkar
- Department of Gastrointestinal and Hepatobiliary Surgery, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Gurudutt P Varty
- Department of Gastrointestinal and Hepatobiliary Surgery, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Niket Shah
- Department of Gastrointestinal and Hepatobiliary Surgery, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Karthik Velmurugan
- Department of Gastrointestinal and Hepatobiliary Surgery, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Mahesh Goel
- Department of Gastrointestinal and Hepatobiliary Surgery, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
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Samuel D, De Martin E, Berg T, Berenguer M, Burra P, Fondevila C, Heimbach JK, Pageaux GP, Sanchez-Fueyo A, Toso C. EASL Clinical Practice Guidelines on liver transplantation. J Hepatol 2024; 81:1040-1086. [PMID: 39487043 DOI: 10.1016/j.jhep.2024.07.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 07/30/2024] [Indexed: 11/04/2024]
Abstract
Liver transplantation (LT) is an established life-saving procedure. The field of LT has changed in the past 10 years from several perspectives, with the expansion of indications, transplantation of patients with acute-on-chronic liver failure, evolution of transplant oncology, the use of donations after cardiac death, new surgical techniques, and prioritisation of recipients on the waiting list. In addition, the advent of organ perfusion machines, the recognition of new forms of rejection, and the attention paid to the transition from paediatric to adult patients, have all improved the management of LT recipients. The purpose of the EASL guidelines presented here is not to cover all aspects of LT but to focus on developments since the previous EASL guidelines published in 2016.
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Bhatti ABH, Dar FS, Altaf A, Rana A, Nazer R, Zia HH, Khan NY, Salih M, Shah NH, Khan NA. Living donor liver transplantation for hepatocellular carcinoma using expanded criteria and alpha-fetoprotein threshold of 1000 ng/mL. J Gastrointest Surg 2024; 28:2084-2089. [PMID: 39389241 DOI: 10.1016/j.gassur.2024.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 09/30/2024] [Accepted: 10/05/2024] [Indexed: 10/12/2024]
Abstract
BACKGROUND New guidelines propose a minimum 5-year survival of 60% for hepatocellular carcinoma (HCC) with living donor liver transplantation (LDLT). This study aimed to evaluate the 5- and 10-year survival rates after transplantation for the expanded criteria for HCC. METHODS This single-center retrospective cohort study included 208 patients who underwent LDLT for the expanded criteria (the largest tumor diameter of ≤10 cm, any tumor number, and alpha-fetoprotein [AFP] level of <1000 ng/mL) and analyzed 5- and 10-year overall survival (OS) and recurrence risk (RR) rates. RESULTS With a median follow-up of 65.1 months (IQR, 19.1-80.2), the 5- and 10-year OS and RR rates were 67.0% and 61.0% and 20.5% and 22.5%, respectively. The largest tumor diameter of >6 cm (hazard ratio [HR], 3.7; 95% CI, 1.7-8.2; P = .001) and AFP level of >400 ng/mL (HR, 4.0; 95% CI, 1.8-9.0; P = .001) were predictors of recurrence. Patients outside the Milan criteria (MC) were grouped into low- and high-risk HCC based on tumor size and AFP level. For low-risk HCC (tumor size of <6 cm, any tumor number, and AFP level of <400 ng/mL), the 5-year RR was comparable to the MC and increased the transplant pool by 35.7% (P > .5). The median number of tumors and the rate of microvascular invasion in the high-risk group, low-risk group, and MC were 2.0 (1.0-3.2), 4.0 (2.0-5.0), and 1.0 (1.0-2.0) (P < .001) and 72.2% (13/18), 44.0% (22/50), and 22.8% (32/140) (P < .001), respectively. CONCLUSION The expanded criteria met the benchmark for 5-year survival. LDLT for the low-risk HCC in the expanded criteria was associated with an acceptable RR.
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Affiliation(s)
- Abu Bakar Hafeez Bhatti
- Department of Hepatobiliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Islamabad, Pakistan; Shifa Tameer-e-Millat University, Islamabad, Pakistan.
| | - Faisal Saud Dar
- Department of Hepatobiliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Islamabad, Pakistan
| | - Abdullah Altaf
- Department of Hepatobiliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Islamabad, Pakistan
| | - Atif Rana
- Department of Radiology, Shifa International Hospital Islamabad, Islamabad, Pakistan
| | - Rashid Nazer
- Department of Radiology, Shifa International Hospital Islamabad, Islamabad, Pakistan
| | - Haseeb Haider Zia
- Department of Hepatobiliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Islamabad, Pakistan
| | - Nusrat Yar Khan
- Department of Hepatobiliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Islamabad, Pakistan
| | - Mohammad Salih
- Department of Gastroenterology and Hepatology, Shifa International Hospital Islamabad, Islamabad, Pakistan
| | - Najmul Hassan Shah
- Department of Gastroenterology and Hepatology, Shifa International Hospital Islamabad, Islamabad, Pakistan
| | - Nasir Ayub Khan
- Department of Anesthesiology, Shifa International Hospital Islamabad, Islamabad, Pakistan
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Altaf A, Mustafa A, Dar A, Nazer R, Riyaz S, Rana A, Bhatti ABH. Artificial intelligence-based model for the recurrence of hepatocellular carcinoma after liver transplantation. Surgery 2024; 176:1500-1506. [PMID: 39181726 DOI: 10.1016/j.surg.2024.07.039] [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: 02/28/2024] [Revised: 07/25/2024] [Accepted: 07/27/2024] [Indexed: 08/27/2024]
Abstract
BACKGROUND Artificial intelligence-based models might improve patient selection for liver transplantation in hepatocellular carcinoma. The objective of the current study was to develop artificial intelligence-based deep learning models and determine the risk of recurrence after living donor liver transplantation for hepatocellular carcinoma. METHODS The study was a single-center retrospective cohort study. Patients who underwent living donor liver transplantation for hepatocellular carcinoma were divided into training and validation cohorts (n = 192). The deep learning models were used to stratify patients in the training cohort into low- and high-risk groups, and 5-year recurrence-free survival was assessed in the validation cohort. RESULTS The median follow-up period was 59.1 (33.9-72.4) months. The artificial intelligence model (pretransplant factors) had an area under the curve of 0.86 in the training cohort and 0.71 in the validation cohort. The largest tumor diameter and alpha-fetoprotein level had the greatest Shapley Additive exPlanations values for recurrence (>0.4). The 5-year recurrence-free survival rates in the low- and high-risk groups were 92.6% and 45% (P < .001). In the second artificial intelligence model (pretransplant factors + grade), the area under the curve for the validation cohort was 0.77, with 5-year recurrence-free survival rates of 96% and 30% in the low- and high-risk groups (P < .001). None of the low-risk patients outside the Milan and University of California San Francisco Criteria had recurrence during follow-up. CONCLUSIONS The artificial intelligence-based hepatocellular carcinoma transplant recurrence models might improve patient selection for liver transplantation.
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Affiliation(s)
- Abdullah Altaf
- King Edward Medical University, Lahore, Pakistan; Department of HPB and Liver Transplant Surgery, Shifa International Hospital, Islamabad, Pakistan. https://twitter.com/abdullahaltaf97
| | - Ahmed Mustafa
- Department of Robotics and Artificial Intelligence, National University of Science and Technology, Islamabad, Pakistan
| | - Abdullah Dar
- Department of HPB and Liver Transplant Surgery, Shifa International Hospital, Islamabad, Pakistan
| | - Rashid Nazer
- Department of Radiology, Shifa International Hospital, Islamabad, Pakistan
| | - Shahzad Riyaz
- Department of Gastroenterology and Hepatology, Shifa International Hospital, Islamabad, Pakistan. https://twitter.com/shahzadriyaz
| | - Atif Rana
- Department of Radiology, Shifa International Hospital, Islamabad, Pakistan. https://twitter.com/atifranaIR
| | - Abu Bakar Hafeez Bhatti
- Department of HPB and Liver Transplant Surgery, Shifa International Hospital, Islamabad, Pakistan; Department of Surgery, Shifa Tameer-e-Millat University, Islamabad, Pakistan.
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He C, Shen W, Lin Z, Hu Z, Li H, Chen H, Yang M, Yang X, Zhuo J, Pan L, Wei X, Zhuang L, Zheng S, Lu D, Xu X. Model for end-stage liver disease-dependent prognostic capacity of platelet-to-lymphocyte ratio following liver transplantation for hepatocellular carcinoma. Transpl Immunol 2024; 85:102071. [PMID: 38866187 DOI: 10.1016/j.trim.2024.102071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 06/04/2024] [Accepted: 06/07/2024] [Indexed: 06/14/2024]
Abstract
BACKGROUND To improve liver organ allocation, the model for end-stage liver disease (MELD) score was adopted in candidates reflecting the severity of liver disease and the physical condition of patients. Inflammatory markers are prognostic factors for various cancers and play prognostic roles in patients after liver transplantation (LT) for hepatocellular carcinoma (HCC). Researchers focused more on pre-LT inflammatory markers, while the role of dynamic change of these inflammatory markers is still unknown. The purpose of this study was to estimate the prognostic value of pre-LT and post-LT inflammatory markers. MATERIAL AND METHODS We collected the pre-LT complete blood count and the post-LT result with highest count of white blood cells within 48 h. Platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio and systemic immune-inflammation index were calculated, and their prognostic roles were analyzed for their MELD scores. RESULTS This retrospective two-center cohort study enrolled 290 patients after LT for HCC. Multivariate analysis identified pre-LT PLR as independent risk factor for recurrence-free survival (RFS) [HR (95%CI): 1.002 (1.000-1.003), p = 0.023]. A high pre-LT PLR or post-LT PLR were associated with poorer RFS (p < 0.001 and p = 0.004, respectively). Based on the MELD scores, the pre-LT PLR value was able to predict the RFS in high MELD group (p < 0.001) but had no predictive power in low MELD group (p = 0.076). On the contrary, the post-LT PLR value was better to predict the overall RFS value in low MELD group (p = 0.007) but could not predict the overall RFS value in high MELD group (p = 0.136). CONCLUSIONS Both pre-LT PLR and post-LT PLR demonstrated prognostic value in patients following LT for HCC. Monitoring PLR values based on the MELD score can improve the predictive prognosis and more effectively guide the individual decisions for the postoperative intervention.
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Affiliation(s)
- Chiyu He
- Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China; Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China
| | - Wei Shen
- Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China
| | - Zuyuan Lin
- Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China; Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou First People's Hospital, Hangzhou, China
| | - Zhihang Hu
- Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China
| | - Huigang Li
- Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China
| | - Hao Chen
- Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China
| | - Modan Yang
- Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China
| | - Xinyu Yang
- Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China; Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou First People's Hospital, Hangzhou, China
| | - Jianyong Zhuo
- Department of Hepatobiliary and Pancreatic Surgery, Hangzhou First People's Hospital, Hangzhou, China
| | - Linhui Pan
- Department of Hepatobiliary and Pancreatic Surgery, Hangzhou First People's Hospital, Hangzhou, China
| | - Xuyong Wei
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China; Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China
| | - Li Zhuang
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, China
| | - Shusen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
| | - Di Lu
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China; Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
| | - Xiao Xu
- Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China; School of Clinical Medicine, Hangzhou Medical College, Hangzhou, China.
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Pang NQ, Chan ACY, Kow AWC. Trends of liver transplantation in Asia. Updates Surg 2024:10.1007/s13304-024-01924-1. [PMID: 39046632 DOI: 10.1007/s13304-024-01924-1] [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: 03/20/2024] [Accepted: 06/18/2024] [Indexed: 07/25/2024]
Abstract
Liver transplantation (LT) in Asia started comparatively early in 1964, just 1 year after Starzl's trail-blazing first attempt. Despite the quick start, LT was slow to develop in this region. Limited access to universal healthcare, lack of public understanding and support as well as the absence of strong legislation, on a backdrop of a wide range of diverse social, religious, economic and cultural background are all contributory factors. Through strong administrative efforts, the number of DDLTs in selected Asian countries has been slowly rising in recent years. However, Asians are generally still less likely to donate organs than Caucasians after death. The strong demand for LT with limited access to deceased organs has, therefore, led to constant need for innovation in LT this region, with the pioneering of various LDLT techniques and safe expansion of donor pool being driven primarily by Asian centers. Familiarity and the development of technical expertise in donor surgery have also resulted in Asian centers repeatedly pushing the boundaries on minimally invasive donor and recipient surgery. In this article, we focus on the past and present states of LT in Asia and explore the future trends of LT in this region.
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Affiliation(s)
- Ning Qi Pang
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, National University Hospital, National University Health System, NUHS Tower Block, 1E, Kent Ridge Road, Level 8, Singapore, 119228, Singapore
- National University Centre for Organ Transplantation (NUCOT), National University Hospital, National University Health System, Singapore, Singapore
| | - Albert C Y Chan
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong SAR, China
| | - Alfred Wei Chieh Kow
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, National University Hospital, National University Health System, NUHS Tower Block, 1E, Kent Ridge Road, Level 8, Singapore, 119228, Singapore.
- National University Centre for Organ Transplantation (NUCOT), National University Hospital, National University Health System, Singapore, Singapore.
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
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9
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Bekki Y, Itoh S, Toshima T, Shimokawa M, Yoshizumi T. Validation of Japanese indication criteria for deceased donor liver transplantation for hepatocellular carcinoma: Analysis of US national registry data. Hepatol Res 2024; 54:695-705. [PMID: 38308638 DOI: 10.1111/hepr.14017] [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: 09/25/2023] [Revised: 01/08/2024] [Accepted: 01/10/2024] [Indexed: 02/05/2024]
Abstract
AIM The Japanese indication criteria for liver transplantation (LT) for hepatocellular carcinoma (HCC) have been updated based on living donor LT data to include either the Milan criteria (MC) or the 5-5-500 rule, which requires a nodule size of ≤5 cm, ≤5 nodules, and an alpha-fetoprotein (AFP) level ≤500 ng/mL. We aimed to validate the 5-5-500 rule and the MC for deceased donor LT (DDLT). METHODS Using national registry data from the United States from 2010 to 2014, we separated DDLT patients into four groups based on the MC and the 5-5-500 rule. The AFP values were stratified into categories: ≤100, 101-300, 301-500, and >500 ng/mL. RESULTS The 5-year survival rate was significantly lower for patients in the groups within MC/beyond 5-5-500 (56.3%) or beyond MC/5-5-500 (60.7%) than for patients in the groups within MC/5-5-500 (76.2%) and beyond MC/within 5-5-500 (72.3%) (p < 0.01). Hepatocellular carcinoma recurrence at 5 years was highest for the within MC/beyond 5-5-500 (25.4%) group, followed by the beyond MC/within 5-5-500 (13.1%), beyond MC/5-5-500 (9.6%), and within MC/5-5-500 (7.4%) groups. The stratified 5-year survival rates after DDLT were 76.5%, 72.4%, 58.4%, and 55.6% in the AFP ≤100, 101-300, 301-500, and >500 categories, respectively (p < 0.01). CONCLUSION The 5-5-500 rule guides the appropriate selection of patients with HCC for DDLT. Patients with AFP levels from 300 to 500 ng/mL had inferior outcomes even when they met the 5-5-500 rule, so further investigation is needed to guide their treatment.
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Affiliation(s)
- Yuki Bekki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takeo Toshima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Mototsugu Shimokawa
- Department of Biostatistics, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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10
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Mehta N, Kelley RK, Yao FY. Refining the approach to down-staging of HCC prior to liver transplantation: Patient selection, loco-regional treatments, and systemic therapies. Hepatology 2024; 80:238-253. [PMID: 37183865 DOI: 10.1097/hep.0000000000000452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 04/20/2023] [Indexed: 05/16/2023]
Affiliation(s)
- Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California, USA
| | - R Katie Kelley
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA
| | - Francis Y Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California, USA
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, California, USA
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11
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Yao S, Yagi S, Sugimoto T, Asahara T, Uemoto S, Hatano E. Occult bacteremia in living donor liver transplantation: a prospective observational study of recipients and donors. Surg Today 2024; 54:596-605. [PMID: 38072872 DOI: 10.1007/s00595-023-02778-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Accepted: 10/01/2023] [Indexed: 05/21/2024]
Abstract
PURPOSE To investigate the incidence and clinical impact of occult bacteremia in liver transplantation (LT). METHODS This prospective observational study involved a fixed-point observation for up to 2 weeks after living donor LT in 20 recipients, with 20 donors as comparison subjects. Bacteria in the blood samples were detected using the ribosomal RNA-targeted reverse-transcription quantitative polymerase chain reaction method. To identify the causality with the gut microbiota (GM), fecal samples were collected and analyzed simultaneously. RESULTS Occult bacteremia was identified in four recipients (20%) and three donors (15%) before the operation, and in seven recipients (35%) and five donors (25%) after the operation. Clostridium leptum subgroup, Prevotella, Colinesella, Enterobacteriaceae, and Streptococcus were the main pathogens responsible. Although it did not negatively affect the donor post-hepatectomy outcomes, the recipients with occult bacteremia had a higher rate of infectious complications post-LT. The GM analyses showed fewer post-LT predominant obligate anaerobes in both the recipients and donors with occult bacteremia. CONCLUSIONS Occult bacteremia is a common condition that occurs in both donors and recipients. While occult bacteremia generally remains subclinical in the healthy population, there is potential risk of the development of an apparent post-LT infection in recipients who are highly immunosuppressed.
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Affiliation(s)
- Siyuan Yao
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
- The Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, USA.
| | - Shintaro Yagi
- Department of Surgery, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Takuya Sugimoto
- Yakult Central Institute, Yakult Honsha Co. Ltd., Tokyo, Japan
| | - Takashi Asahara
- Yakult Central Institute, Yakult Honsha Co. Ltd., Tokyo, Japan
| | - Shinji Uemoto
- Shiga University of Medical Science, Otsu, Shiga, Japan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
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12
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Zhou Z, Liu Q, Liu J, Li W, Cao S, Xu J, Chen J, Xu X, Chen C. Research progress of protein induced by vitamin K absence or antagonist II in liver transplantation for hepatocellular carcinoma. Heliyon 2024; 10:e30622. [PMID: 38726103 PMCID: PMC11079398 DOI: 10.1016/j.heliyon.2024.e30622] [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: 01/27/2024] [Revised: 04/30/2024] [Accepted: 04/30/2024] [Indexed: 05/12/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common pathologic type of primary liver cancer. Liver transplantation (LT) is a radical strategy for treating patients with early-stage HCC, which may lead to a better prognosis compared to hepatectomy and ablation. However, survival of patients who develop HCC recurrence after LT is short, and early recurrence is the most common cause of death. Thus, efficient biomarkers are also needed in LT to guide precision therapy to improve patient prognosis and 5-year survival. Protein induced by vitamin K absence or antagonist II (PIVKA-II) is an abnormal prothrombin that cannot activate coagulation, and it is significantly increased in patients with HCC, obstructive jaundice, and those taking vitamin K antagonists. Over the past decades, substantial progress has been made in the study of PIVKA-II in diagnosing, surveilling, and treating HCC, but its role in LT still needs to be elaborated. In this review, we focused on the role of PIVKA-II as a biomarker in LT for HCC, especially its relationship with clinicopathologic features, early recurrence, long-term survival, and donor-recipient selection.
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Affiliation(s)
- Zheyu Zhou
- Department of General Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, China
| | - Qiaoyu Liu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Jinsong Liu
- Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Colorectal Cancer Research Center, Shanghai, China
| | - Wenwen Li
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Shuya Cao
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Science, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China
| | - Jiawei Xu
- Department of Hepatobiliary and Transplantation Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Jun Chen
- Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Xiaoliang Xu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Chaobo Chen
- Department of General Surgery, Xishan People's Hospital of Wuxi City, Wuxi, China
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13
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Al-Hasan M, Mehta N, Yang JD, Singal AG. Role of biomarkers in the diagnosis and management of HCC. Liver Transpl 2024:01445473-990000000-00379. [PMID: 38738964 DOI: 10.1097/lvt.0000000000000398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 05/06/2024] [Indexed: 05/14/2024]
Abstract
For many cancers, biomarkers have served as an important tool across the cancer care continuum from risk stratification and early detection to diagnosis and treatment. Alpha-fetoprotein (AFP) remains one of the few validated biomarkers for patients with HCC. Although AFP has shown potential for each of these steps, its performance, when used alone, has often been suboptimal. There continue to be discordant recommendations about AFP's value when combined with ultrasound for surveillance, as well as its role in diagnostic algorithms. Conversely, high AFP levels are associated with aggressive tumor biology and survival, so it remains a key factor for the selection of candidates for liver transplant. There have been immense efforts to identify and validate additional biomarkers for each of these steps in the HCC care continuum. Indeed, biomarker panels have shown promising data for HCC risk stratification and surveillance among patients with cirrhosis, as well as prognostication and detection of minimal residual disease in patients undergoing HCC treatment. Several large prospective studies are currently ongoing to evaluate the role of these emerging biomarkers in clinical practice.
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Affiliation(s)
- Mohammed Al-Hasan
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Neil Mehta
- Department of Internal Medicine, University of California San Francisco, San Francisco, California, USA
| | - Ju Dong Yang
- Department of Internal Medicine, Cedars Sinai, Los Angeles, California, USA
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
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14
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Kim DS, Yoon YI, Kim BK, Choudhury A, Kulkarni A, Park JY, Kim J, Sinn DH, Joo DJ, Choi Y, Lee JH, Choi HJ, Yoon KT, Yim SY, Park CS, Kim DG, Lee HW, Choi WM, Chon YE, Kang WH, Rhu J, Lee JG, Cho Y, Sung PS, Lee HA, Kim JH, Bae SH, Yang JM, Suh KS, Al Mahtab M, Tan SS, Abbas Z, Shresta A, Alam S, Arora A, Kumar A, Rathi P, Bhavani R, Panackel C, Lee KC, Li J, Yu ML, George J, Tanwandee T, Hsieh SY, Yong CC, Rela M, Lin HC, Omata M, Sarin SK. Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation. Hepatol Int 2024; 18:299-383. [PMID: 38416312 DOI: 10.1007/s12072-023-10629-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 12/18/2023] [Indexed: 02/29/2024]
Abstract
Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
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Affiliation(s)
- Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | | | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University College of Medicine, Yangsan, Republic of Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Cheon-Soo Park
- Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Deok-Gie Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Eun Chon
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Ilsan, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Soek Siam Tan
- Department of Medicine, Hospital Selayang, Batu Caves, Selangor, Malaysia
| | - Zaigham Abbas
- Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - Ananta Shresta
- Department of Hepatology, Alka Hospital, Lalitpur, Nepal
| | - Shahinul Alam
- Crescent Gastroliver and General Hospital, Dhaka, Bangladesh
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Pravin Rathi
- TN Medical College and BYL Nair Hospital, Mumbai, India
| | - Ruveena Bhavani
- University of Malaya Medical Centre, Petaling Jaya, Selangor, Malaysia
| | | | - Kuei Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jun Li
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Ming-Lung Yu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | | | | | | | | | - H C Lin
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Bunkyo City, Japan
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15
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Gonçalves-Reis M, Proença D, Frazão LP, Neto JL, Silva S, Pinto-Marques H, Pereira-Leal JB, Cardoso J. Analytical validation and algorithm improvement of HepatoPredict kit to assess hepatocellular carcinoma prognosis before a liver transplantation. Pract Lab Med 2024; 39:e00365. [PMID: 38371895 PMCID: PMC10869278 DOI: 10.1016/j.plabm.2024.e00365] [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: 08/01/2023] [Revised: 01/22/2024] [Accepted: 01/23/2024] [Indexed: 02/20/2024] Open
Abstract
Objectives To verify the analytical performance of the HepatoPredict kit, a novel tool developed to stratify Hepatocellular Carcinoma (HCC) patients according to their risk of relapse after a Liver Transplantation (LT). Methods The HepatoPredict tool combines clinical variables and a gene expression signature in an ensemble of machine-learning algorithms to forecast the benefit of a LT in HCC patients. To ensure the accuracy and reliability of this method, extensive analytical validation was conducted to verify its specificity and robustness. The experiments were designed following the guidelines for multi-target genomic assays such as ISO201395-2019, MIQE, CLSI-MM16, CLSI-MM17, and CLSI-EP17-A. The validation process included reproducibility between operators and between RNA extractions and RT-qPCR runs, and interference of input RNA levels or varying reagent levels. A recently retrained version of the HepatoPredict algorithms was also tested. Results The validation process demonstrated that the HepatoPredict kit met the required standards for robustness (p > 0.05), analytical specificity (inclusivity of 95 %), and sensitivity (LoB, LoD, linear range, and amplification efficiency between 90 and 110 %). The operator, equipment, input RNA, and reagents used had no significant effect on the HepatoPredict results. Additionally, the testing of a recently retrained version of the HepatoPredict algorithm, showed that this new version further improved the accuracy of the kit and performed better than existing clinical criteria in accurately identifying HCC patients who are more likely to benefit LT. Conclusions Even with the introduced variations in molecular and clinical variables, the HepatoPredict kit's prognostic information remains consistent. It can accurately identify HCC patients who are more likely to benefit from a LT. Its robust performance also confirms that it can be easily integrated into standard diagnostic laboratories.
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Affiliation(s)
| | | | | | - João L. Neto
- Ophiomics – Precision Medicine, Lisbon, Portugal
| | - Sílvia Silva
- Hepato-Biliary-Pancreatic and Transplantation Centre, Curry Cabral Hospital, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
| | - Hugo Pinto-Marques
- Hepato-Biliary-Pancreatic and Transplantation Centre, Curry Cabral Hospital, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
- Chronic Diseases Research Center (CEDOC), NOVA Medical School, Universidade NOVA de Lisboa (NMS/UNL), Lisbon, Portugal
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16
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Horwitz JK, Agopian VG. Indication of Liver Transplant for HCC: Current Status and Future Directions. CURRENT HEPATOLOGY REPORTS 2024; 23:185-192. [DOI: 10.1007/s11901-024-00641-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/10/2024] [Indexed: 01/03/2025]
Abstract
Abstract
Purpose of Review
Liver transplantation remains the gold-standard treatment for cirrhotic patients with early stage, surgically unresectable hepatocellular carcinoma (HCC). In this review, we describe the current state of liver transplantation (LT) for HCC.
Recent Findings
We review recent advances in expanded indications for LT, diagnostics with liquid biopsy and biomarkers, and the emerging role of immunotherapy in this patient population.
Summary
Although the shortage of liver allografts necessitates a restrictive HCC selection policy, future advances in patient selection, liquid biopsy technologies and systemic therapies have the potential to improve access to liver transplantation even in patients with expanded indications, without compromising on post-transplant outcomes.
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17
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Yoshitomi K, Hayashi T, Oe S, Shibata M, Honma Y, Harada M, Kooka Y. Child-Pugh grade deterioration stratified by the etiology after transcatheter arterial chemoembolization as initial treatment for hepatocellular carcinoma. Sci Rep 2024; 14:3707. [PMID: 38355630 PMCID: PMC10867004 DOI: 10.1038/s41598-024-53709-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 02/04/2024] [Indexed: 02/16/2024] Open
Abstract
Transcatheter arterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). However, TACE can cause deterioration of liver functions. We aimed to identify the factors that influence deterioration of liver function after TACE. We retrospectively analyzed 262 patients who underwent TACE as initial treatment for HCC with Child-Pugh grade A. We divided them into three groups stratified by the etiology of underlying liver disease. Patients were classified into hepatitis B virus (HBV) group, hepatitis C virus (HCV) group, and non-HBV / non-HCV (NBNC) group. Liver functions at one month after TACE and time to Child-Pugh grade B or C were compared between the three groups. The HBV, HCV and NBNC groups contained 23, 123 and 116 patients, respectively. The decline in albumin level after TACE was significantly higher in NBNC group than other groups (p = 0.02). NBNC group showed a shorter time to Child-Pugh grade deterioration compared with HBV group and HCV group (p < 0.001). Multivariate Cox regression analysis showed that NBNC group was a significant factor for Child-Pugh grade deterioration (Hazard ratio 3.74, 95% confidence interval 1.89-7.40, p < 0.001). These results revealed that liver functions worsened most remarkably in NBNC group after TACE.
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Affiliation(s)
- Kengo Yoshitomi
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Tsuguru Hayashi
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
- Department of Hepatology, Sendai Kousei Hospital, 4-15 Hirosemachi, Aoba-Ku, Sendai, 980-0873, Japan.
| | - Shinji Oe
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Michihiko Shibata
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Yuichi Honma
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Masaru Harada
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Yohei Kooka
- Department of Hepatology, Sendai Kousei Hospital, 4-15 Hirosemachi, Aoba-Ku, Sendai, 980-0873, Japan
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18
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Martínez-Blanco P, Suárez M, Gil-Rojas S, Torres AM, Martínez-García N, Blasco P, Torralba M, Mateo J. Prognostic Factors for Mortality in Hepatocellular Carcinoma at Diagnosis: Development of a Predictive Model Using Artificial Intelligence. Diagnostics (Basel) 2024; 14:406. [PMID: 38396445 PMCID: PMC10888215 DOI: 10.3390/diagnostics14040406] [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: 12/31/2023] [Revised: 01/24/2024] [Accepted: 02/09/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) accounts for 75% of primary liver tumors. Controlling risk factors associated with its development and implementing screenings in risk populations does not seem sufficient to improve the prognosis of these patients at diagnosis. The development of a predictive prognostic model for mortality at the diagnosis of HCC is proposed. METHODS In this retrospective multicenter study, the analysis of data from 191 HCC patients was conducted using machine learning (ML) techniques to analyze the prognostic factors of mortality that are significant at the time of diagnosis. Clinical and analytical data of interest in patients with HCC were gathered. RESULTS Meeting Milan criteria, Barcelona Clinic Liver Cancer (BCLC) classification and albumin levels were the variables with the greatest impact on the prognosis of HCC patients. The ML algorithm that achieved the best results was random forest (RF). CONCLUSIONS The development of a predictive prognostic model at the diagnosis is a valuable tool for patients with HCC and for application in clinical practice. RF is useful and reliable in the analysis of prognostic factors in the diagnosis of HCC. The search for new prognostic factors is still necessary in patients with HCC.
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Affiliation(s)
| | - Miguel Suárez
- Gastroenterology Department, Virgen de la Luz Hospital, 16002 Cuenca, Spain
- Medical Analysis Expert Group, Institute of Technology, Universidad de Castilla-La Mancha, 16071 Cuenca, Spain
- Medical Analysis Expert Group, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
| | - Sergio Gil-Rojas
- Gastroenterology Department, Virgen de la Luz Hospital, 16002 Cuenca, Spain
| | - Ana María Torres
- Medical Analysis Expert Group, Institute of Technology, Universidad de Castilla-La Mancha, 16071 Cuenca, Spain
- Medical Analysis Expert Group, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
| | | | - Pilar Blasco
- Department of Pharmacy, General University Hospital, 46014 Valencia, Spain
| | - Miguel Torralba
- Internal Medicine Unit, Guadalajara University Hospital, 19002 Guadalajara, Spain (M.T.)
- Faculty of Medicine, Universidad de Alcalá de Henares, 28801 Alcalá de Henares, Spain
- Translational Research Group in Cellular Immunology (GITIC), Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
| | - Jorge Mateo
- Medical Analysis Expert Group, Institute of Technology, Universidad de Castilla-La Mancha, 16071 Cuenca, Spain
- Medical Analysis Expert Group, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
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19
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Loosen SH, Leyh C, Neumann UP, Bock H, Weigel C, Luedde T, Roderburg C. Liver transplantation meets gastrointestinal cancer. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:62-72. [PMID: 38195110 DOI: 10.1055/a-2226-0123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2024]
Abstract
Liver transplantation (LT) has emerged as a standard of care for patients with end-stage liver disease, providing a life-saving intervention for patients with severely compromised liver function in both the acute and chronic setting. While LT has also become a routine procedure for early-stage hepatocellular carcinoma (HCC), offering a potential cure by treating both the tumor and the underlying liver disease, its relevance in the context of other malignancies such as cholangiocellular carcinoma (CCA), combined hepatocellular-cholangiocarcinoma (cHCC-CCA) or liver metastases is still the subject of intense debate and no definite recommendations have yet been established. This review summarizes the current therapeutic standards in the context of LT for gastrointestinal malignancies and provides a reflection and outlook on current scientific and clinical developments.
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Affiliation(s)
- Sven H Loosen
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
| | - Catherine Leyh
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
| | - Ulf Peter Neumann
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Aachen, Germany
- Department of Surgery and Transplantation, University Hospital Essen, Essen, Germany
| | - Hans Bock
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
| | - Christian Weigel
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Tom Luedde
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
| | - Christoph Roderburg
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
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20
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He X, Xu S, Tang L, Ling S, Wei X, Xu X. Insights into the history and tendency of liver transplantation for liver cancer: a bibliometric-based visual analysis. Int J Surg 2024; 110:406-418. [PMID: 37800536 PMCID: PMC10793788 DOI: 10.1097/js9.0000000000000806] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 09/18/2023] [Indexed: 10/07/2023]
Abstract
Research on liver transplantation (LT) for liver cancer has gained increasing attention. This paper has comprehensively described the current status, hotspots and trends in this field. A total of 2991 relevant articles from 1 January 1963 to 28 February 2023 were obtained from the Web of Science Core Collection. VOSviewer and CiteSpace software were utilized as bibliometric tools to analyze and visualize knowledge mapping. Between 1963 and 2023, the number of papers in the area of LT for liver cancer increased continuously. A total of 70 countries/regions, 2303 institutions and 14 840 researchers have published research articles, with the United States and China being the two most productive countries. Our bibliometric-based visual analysis revealed the expansion of LT indications for liver cancer and the prevention/treatment of cancer recurrence as ongoing research hotspots over the past decades. Meanwhile, emerging studies also focus on downstaging/bridging treatments before LT and the long-term survival of LT recipient, in particular the precise application of immunosuppressants.
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Affiliation(s)
- Xinyu He
- The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine
| | - Shengjun Xu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine
| | - Linsong Tang
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
- Zhejiang University School of Medicine
| | - Sunbin Ling
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine
| | - Xuyong Wei
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine
| | - Xiao Xu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
- Zhejiang University School of Medicine
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou, People’s Republic of China
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21
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Yilma M, Mehta N. Optimal Liver Transplantation Criteria for Hepatocellular Carcinoma. Surg Oncol Clin N Am 2024; 33:133-142. [PMID: 37945139 DOI: 10.1016/j.soc.2023.06.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2023]
Abstract
Liver transplantation continues to be the optimal treatment for hepatocellular carcinoma (HCC). Given the limited organ supply, patient selection for liver transplant must carefully balance tumor progression with risk of recurrence posttransplant. There are several pretransplant selection criteria that incorporate biomarkers as well as imaging modality to risk-stratify patients as we continue to look for the optimal transplant cutoff for patients with HCC, which should be transplant-center specific, and account for organ availability and dynamic response to locoregional therapy.
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Affiliation(s)
- Mignote Yilma
- Department of Surgery, University of California San Francisco, 513 Parnassus Avenue, S-321, San Francisco, CA 94143, USA; National Clinician Scholars Program, University of California San Francisco, 513 Parnassus Avenue, S-321, San Francisco, CA 94143, USA. https://twitter.com/mignoteyilmaMD
| | - Neil Mehta
- Department of Medicine, University of California San Francisco, Connie Frank Transplant Center, 400 Parnassus Avenue 7th Floor, San Francisco, CA 94143, USA.
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22
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Mehta N. Updates in liver transplantation policy for patients with hepatocellular carcinoma (HCC). Clin Liver Dis (Hoboken) 2024; 23:e0157. [PMID: 38681512 PMCID: PMC11049753 DOI: 10.1097/cld.0000000000000157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 02/13/2024] [Indexed: 05/01/2024] Open
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23
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Singal AG, Llovet JM, Yarchoan M, Mehta N, Heimbach JK, Dawson LA, Jou JH, Kulik LM, Agopian VG, Marrero JA, Mendiratta-Lala M, Brown DB, Rilling WS, Goyal L, Wei AC, Taddei TH. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology 2023; 78:1922-1965. [PMID: 37199193 PMCID: PMC10663390 DOI: 10.1097/hep.0000000000000466] [Citation(s) in RCA: 565] [Impact Index Per Article: 282.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Accepted: 05/01/2023] [Indexed: 05/19/2023]
Affiliation(s)
- Amit G. Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Josep M. Llovet
- Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York, USA
- Translational Research in Hepatic Oncology, Liver Unit, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic, University of Barcelona, Catalonia, Spain
- Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain
| | - Mark Yarchoan
- Department of Medical Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA
| | - Neil Mehta
- University of California, San Francisco, San Francisco, California, USA
| | | | - Laura A. Dawson
- Radiation Medicine Program/University Health Network, Department of Radiation Oncology, University of Toronto, Toronto, Canada
| | - Janice H. Jou
- Division of Gastroenterology and Hepatology, Oregon Health and Science University, Portland, Oregon, USA
| | - Laura M. Kulik
- Northwestern Medical Faculty Foundation, Chicago, Illinois, USA
| | - Vatche G. Agopian
- The Dumont–University of California, Los Angeles, Transplant Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA
| | - Jorge A. Marrero
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Mishal Mendiratta-Lala
- Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan, USA
| | - Daniel B. Brown
- Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - William S. Rilling
- Division of Interventional Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Lipika Goyal
- Department of Medicine, Stanford School of Medicine, Palo Alto, California, USA
| | - Alice C. Wei
- Memorial Sloan Kettering Cancer Center, New York City, New York, USA
| | - Tamar H. Taddei
- Department of Medicine (Digestive Diseases), Yale School of Medicine, New Haven, CT, USA
- Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA
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24
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Norman JS, Li PJ, Kotwani P, Shui AM, Yao F, Mehta N. AFP-L3 and DCP strongly predict early hepatocellular carcinoma recurrence after liver transplantation. J Hepatol 2023; 79:1469-1477. [PMID: 37683735 PMCID: PMC10998694 DOI: 10.1016/j.jhep.2023.08.020] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 07/27/2023] [Accepted: 08/22/2023] [Indexed: 09/10/2023]
Abstract
BACKGROUND & AIMS Alpha-fetoprotein (AFP) predicts hepatocellular carcinoma (HCC) recurrence after liver transplant (LT) but remains an imperfect biomarker. The role of DCP (des-gamma-carboxyprothrombin) and AFP-L3 (AFP bound to Lens culinaris agglutinin) in predicting HCC recurrence remains incompletely characterized. AFP-L3 and DCP could identify patients at high risk of post-transplant HCC recurrence and serve as liver transplant exclusion criteria to defer transplant until patients receive additional risk-reducing pre-transplant locoregional therapy. METHODS This prospective cohort study included consecutive patients with HCC who underwent LT (within or down-staged to Milan criteria) between 2017 and 2022. Pre-transplant AFP, AFP-L3, and DCP measurements were obtained. The primary endpoint was the ability of biomarkers to predict HCC recurrence-free survival. RESULTS This cohort included 285 patients with a median age of 67 (IQR 63-71). At LT, median biomarker values were AFP 5.0 ng/ml (IQR 3.0-12.1), AFP-L3 6.7% (0.5-13.2), and DCP 1.0 ng/ml (0.3-2.8). Most (94.7%) patients received pre-LT locoregional therapy. After a median post-LT follow-up of 3.1 years, HCC recurrence was observed in 18 (6.3%) patients. AFP-L3 and DCP outperformed AFP with C-statistics of 0.81 and 0.86 respectively, compared with 0.74 for AFP. A dual-biomarker combination of AFP-L3 ≥15% and DCP ≥7.5 predicted 61.1% of HCC recurrences, whereas HCC only recurred in 7 of 265 (2.6%) patients not meeting this threshold. The Kaplan-Meier recurrence-free survival rate at 3 years post-LT was 43.7% for patients with dual-positive biomarkers compared to 97.0% for all others (p <0.001). CONCLUSIONS Dual-positivity for AFP-L3 ≥15% and DCP ≥7.5 strongly predicted post-LT HCC recurrence. This model could refine LT selection criteria and identify high-risk patients who require additional locoregional therapy prior to LT. IMPACT AND IMPLICATIONS Alpha-fetoprotein (AFP) is used to predict hepatocellular carcinoma (HCC) recurrence after liver transplant, but it remains an imperfect biomarker. In this prospective study, the biomarkers DCP (des-gamma-carboxyprothrombin) and AFP-L3 (AFP bound to Lens culinaris agglutinin) strongly predicted early HCC recurrence and outperformed AFP. A dual-biomarker combination of AFP-L3 ≥15% and DCP ≥7.5 predicted the majority of recurrences and could be used to further refine liver transplant eligibility criteria.
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Affiliation(s)
- Joshua S Norman
- University of California San Francisco School of Medicine, San Francisco, CA, USA; Department of Internal Medicine, Stanford, CA, USA
| | - P Jonathan Li
- University of California San Francisco School of Medicine, San Francisco, CA, USA
| | - Prashant Kotwani
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California, USA
| | - Amy M Shui
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
| | - Francis Yao
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California, USA
| | - Neil Mehta
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
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25
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Li X, Bao H, Shi Y, Zhu W, Peng Z, Yan L, Chen J, Shu X. Machine learning methods for accurately predicting survival and guiding treatment in stage I and II hepatocellular carcinoma. Medicine (Baltimore) 2023; 102:e35892. [PMID: 37960763 PMCID: PMC10637529 DOI: 10.1097/md.0000000000035892] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Accepted: 10/11/2023] [Indexed: 11/15/2023] Open
Abstract
Accurately predicting survival in patients with early hepatocellular carcinoma (HCC) is essential for making informed decisions about treatment and prognosis. Herein, we have developed a machine learning (ML) model that can predict patient survival and guide treatment decisions. We obtained patient demographic information, tumor characteristics, and treatment details from the SEER database. To analyze the data, we employed a Cox proportional hazards (CoxPH) model as well as 3 ML algorithms: neural network multitask logistic regression (N-MLTR), DeepSurv, and random survival forest (RSF). Our evaluation relied on the concordance index (C-index) and Integrated Brier Score (IBS). Additionally, we provided personalized treatment recommendations regarding surgery and chemotherapy choices and validated models' efficacy. A total of 1136 patients with early-stage (I, II) hepatocellular carcinoma (HCC) who underwent liver resection or transplantation were randomly divided into training and validation cohorts at a ratio of 3:7. Feature selection was conducted using Cox regression analyses. The ML models (NMLTR: C-index = 0.6793; DeepSurv: C-index = 0.7028; RSF: C-index = 0.6890) showed better discrimination in predicting survival than the standard CoxPH model (C-index = 0.6696). Patients who received recommended treatments had higher survival rates than those who received unrecommended treatments. ML-based surgery treatment recommendations yielded higher hazard ratios (HRs): NMTLR HR = 0.36 (95% CI: 0.25-0.51, P < .001), DeepSurv HR = 0.34 (95% CI: 0.24-0.49, P < .001), and RSF HR = 0.37 (95% CI: 0.26-0.52, P = <.001). Chemotherapy treatment recommendations were associated with significantly improved survival for DeepSurv (HR: 0.57; 95% CI: 0.4-0.82, P = .002) and RSF (HR: 0.66; 95% CI: 0.46-0.94, P = .020). The ML survival model has the potential to benefit prognostic evaluation and treatment of HCC. This novel analytical approach could provide reliable information on individual survival and treatment recommendations.
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Affiliation(s)
- Xianguo Li
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Haijun Bao
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yongping Shi
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wenzhong Zhu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zuojie Peng
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lizhao Yan
- Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jinhuang Chen
- Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaogang Shu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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26
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Abdelrahim M, Esmail A, Abudayyeh A, Murakami N, Victor D, Kodali S, Cheah YL, Simon CJ, Noureddin M, Connor A, Saharia A, Moore LW, Heyne K, Kaseb AO, Gaber AO, Ghobrial RM. Transplant Oncology: An Emerging Discipline of Cancer Treatment. Cancers (Basel) 2023; 15:5337. [PMID: 38001597 PMCID: PMC10670243 DOI: 10.3390/cancers15225337] [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: 10/20/2023] [Accepted: 10/30/2023] [Indexed: 11/26/2023] Open
Abstract
Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The applications of oncology, transplant medicine, and surgery are the core of transplant oncology to improve patients' survival and quality of life. The main concept of transplant oncology is to radically cure cancer by removing the diseased organ and replacing it with a healthy one, aiming to improve the survival outcomes and quality of life of cancer patients. Subsequently, it seeks to expand the treatment options and research for hepatobiliary malignancies, which have seen significantly improved survival outcomes after the implementation of liver transplantation (LT). In the case of colorectal cancer (CRC) in the transplant setting, where the liver is the most common site of metastasis of patients who are considered to have unresectable disease, initial studies have shown improved survival for LT treatment compared to palliative therapy interventions. The indications of LT for hepatobiliary malignancies have been slowly expanded over the years beyond Milan criteria in a stepwise manner. However, the outcome improvements and overall patient survival are limited to the specifics of the setting and systematic intervention options. This review aims to illustrate the representative concepts and history of transplant oncology as an emerging discipline for the management of hepatobiliary malignancies, in addition to other emerging concepts, such as the uses of immunotherapy in a peri-transplant setting as well as the use of circulating tumor DNA (ctDNA) for surveillance post-transplantation.
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Affiliation(s)
- Maen Abdelrahim
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (A.E.)
- Cockrell Center of Advanced Therapeutics Phase I Program, Houston Methodist Research Institute, Houston, TX 77030, USA
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Abdullah Esmail
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (A.E.)
| | - Ala Abudayyeh
- Section of Nephrology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Naoka Murakami
- Division of Renal Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA;
| | - David Victor
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Sudha Kodali
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Yee Lee Cheah
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Caroline J. Simon
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Mazen Noureddin
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Ashton Connor
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Ashish Saharia
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Linda W. Moore
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Kirk Heyne
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (A.E.)
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Ahmed O. Kaseb
- Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - A. Osama Gaber
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Rafik Mark Ghobrial
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
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27
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Puri P, Malik S. Liver Transplantation: Contraindication and Ineligibility. J Clin Exp Hepatol 2023; 13:1116-1129. [PMID: 37975058 PMCID: PMC10643298 DOI: 10.1016/j.jceh.2023.04.005] [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: 01/24/2023] [Accepted: 04/14/2023] [Indexed: 11/19/2023] Open
Abstract
Liver transplantation (LT) is a life-saving therapeutic modality for patients with various advanced liver diseases. It is crucial to identify that the patient's illness is sufficiently advanced and unlikely to improve with medical management to justify the need for transplantation. At the same time, it is crucial to identify patients with comorbidities and far advanced disease that would result in an unacceptable outcome after LT. Specific care also is required before deciding on LT in the elderly, acute on chronic liver disease, patients with comorbidities, and hepatocellular carcinoma. Transplantation needs to be timed appropriately to avoid unnecessary LT and ensure that the decision is not left too late to avoid losing the patient without a transplant. Also, important is the decision as to when not to transplant. The current review explores some of these issues of contraindications and ineligibility for LT.
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Affiliation(s)
- Pankaj Puri
- Fortis Escorts Liver and Digestive Diseases Institute, Fortis Escorts Hospital, New Delhi 110025, India
| | - Sarthak Malik
- Department of Gastroenterology, Manipal Hospital, Dwarka, New Delhi 110075, India
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28
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Mehta N, Kotwani P, Norman J, Shui A, Saxena V, Chan W, Yao FY. AFP-L3 and DCP are superior to AFP in predicting waitlist dropout in HCC patients: Results of a prospective study. Liver Transpl 2023; 29:1041-1049. [PMID: 37159217 PMCID: PMC10523909 DOI: 10.1097/lvt.0000000000000149] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 03/28/2023] [Indexed: 05/10/2023]
Abstract
In patients with HCC awaiting liver transplantation (LT), there is a need to identify biomarkers that are superior to AFP in predicting prognosis. AFP-L3 and des-gamma-carboxyprothrombin (DCP) play a role in HCC detection, but their ability to predict waitlist dropout is unknown. In this prospective single-center study commenced in July 2017, 267 HCC patients had all 3 biomarkers obtained at LT listing. Among them, 96.2% received local-regional therapy, and 18.8% had an initial tumor stage beyond Milan criteria requiring tumor downstaging. At listing, median AFP was 7.0 ng/mL (IQR 3.4-21.5), median AFP-L3 was 7.1% (IQR 0.5-12.5), and median DCP was 1.0 ng/mL (IQR 0.2-3.8). After a median follow-up of 19.3 months, 63 (23.6%) experienced waitlist dropout, while 145 (54.3%) received LT, and 59 (22.1%) were still awaiting LT. Using Cox proportional hazards analysis, AFP-L3≥35% and DCP≥7.5 ng/mL were associated with increased waitlist dropout, whereas AFP at all tested cutoffs, including ≥20,≥ 100, and≥250 ng/mL was not. In a multivariable model, AFP-L3≥35% (HR 2.25, p =0.04) and DCP≥7.5 ng/mL (HR 2.20, p =0.02) remained associated with waitlist dropout as did time from HCC diagnosis to listing ≥ 1 year and increasing MELD-Na score. Kaplan-Meier probability of waitlist dropout within 2 years was 21.8% in those with AFP-L3<35% and DCP<7.5 ng/mL, 59.9% with either AFP-L3 or DCP elevated, and 100% for those with both elevated ( p <0.001). In this prospective study, listing AFP-L3% and DCP were superior to AFP in predicting waitlist dropout with the combination of AFP-L3≥35% and DCP≥7.5 ng/mL associated with a 100% risk of waitlist dropout, thus clearly adding prognostic value to AFP alone.
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Affiliation(s)
- Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco
| | - Prashant Kotwani
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco
| | - Joshua Norman
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco
| | - Amy Shui
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA
| | - Varun Saxena
- Department of Gastroenterology and Transplant Hepatology, Kaiser Permanente South San Francisco
| | - Wesley Chan
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco
| | - Francis Y. Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco
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Uemoto Y, Taura K, Yamada Y, Takeda H, Nakano S, Takai A, Haga H, Hatano E. A Rare Case of Donor-Origin Intrahepatic Cholangiocarcinoma After Liver Transplantation for Hepatocellular Carcinoma: A Case Report. Transplant Proc 2023; 55:1964-1967. [PMID: 37550136 DOI: 10.1016/j.transproceed.2023.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 07/19/2023] [Indexed: 08/09/2023]
Abstract
BACKGROUND Tumors may develop in the grafted liver after liver transplantation for hepatocellular carcinoma, most of which are hepatocellular carcinoma recurrences and are rarely of donor origin. We report a rare case of donor-origin intrahepatic cholangiocarcinoma in a liver allograft after liver transplantation for hepatocellular carcinoma. METHODS A man in his 60s underwent liver transplantation for hepatocellular carcinoma with hepatitis C virus cirrhosis. The donor was a braindead woman in her 60s who had no history of malignancy. RESULTS Three years and 5 months after liver transplantation, a tumor developed in the allograft. Computed tomography scans showed a 40-mm tumor that was atypical for hepatocellular carcinoma. Tumor biopsy was most suggestive of intrahepatic cholangiocarcinoma. Fluorescence in situ hybridization of the tumor showed an XX signal pattern, suggesting that it originated from the donor liver. Whole exome sequencing analysis strongly suggested that the tumor was an intrahepatic cholangiocarcinoma derived from the donor. CONCLUSIONS Although donor-origin cancer after liver transplantation is extremely rare, it should be considered for adequate treatment.
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Affiliation(s)
- Yusuke Uemoto
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Surgery, Kokura Memorial Hospital, Kitakyushu, Japan
| | - Kojiro Taura
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Gastroenterological Surgery and Oncology, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan.
| | - Yosuke Yamada
- Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan
| | - Haruhiko Takeda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shigeharu Nakano
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Atsushi Takai
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hironori Haga
- Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan
| | - Etsuro Hatano
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Yoon JH, Choi SK. Management of early-stage hepatocellular carcinoma: challenges and strategies for optimal outcomes. JOURNAL OF LIVER CANCER 2023; 23:300-315. [PMID: 37734717 PMCID: PMC10565545 DOI: 10.17998/jlc.2023.08.27] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 08/24/2023] [Accepted: 08/27/2023] [Indexed: 09/23/2023]
Abstract
Although hepatocellular carcinoma (HCC) is associated with a poor prognosis, management of early-stage HCC is often successful with highly efficacious treatment modalities such as liver transplantation, surgical resection, and radiofrequency ablation. However, unfavorable clinical outcomes have been observed under certain circumstances, even after efficient treatment. Factors that predict unsuitable results after treatment include tumor markers, inflammatory markers, imaging findings reflecting tumor biology, specific outcome indicators for each treatment modality, liver functional reserve, and the technical feasibility of the treatment modalities. Various strategies may overcome these challenges, including the application of reinforced treatment indication criteria with predictive markers reflecting tumor biology, compensation for technical issues with up-to-date technologies, modification of treatment modalities, downstaging with locoregional therapies (such as transarterial chemotherapy or radiotherapy), and recently introduced combination immunotherapies. In this review, we discuss the challenges to achieving optimal outcomes in the management of early-stage HCC and suggest strategies to overcome these obstacles.
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Affiliation(s)
- Jae Hyun Yoon
- Department of Gastroenterology and hepatology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea
| | - Sung Kyu Choi
- Department of Gastroenterology and hepatology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea
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Shannon AH, Ruff SM, Schenk AD, Washburn K, Pawlik TM. Updates and Expert Opinions on Liver Transplantation for Gastrointestinal Malignancies. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1290. [PMID: 37512101 PMCID: PMC10383519 DOI: 10.3390/medicina59071290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 07/12/2023] [Accepted: 07/12/2023] [Indexed: 07/30/2023]
Abstract
Transplant oncology is a relatively new field in which transplantation is used to treat patients who would otherwise be unresectable. New anticancer treatment paradigms using tumor and transplant immunology and cancer immunogenomics are emerging. In turn, liver transplantation (LT) has become a potential therapy for certain patients with colorectal cancer (CRC) with liver metastasis, hepatocellular (HCC), cholangiocarcinoma (CCA), and metastatic neuroendocrine tumor (NET) of the liver. Although there are established criteria for LT in HCC, evidence regarding LT as a treatment modality for certain gastrointestinal malignancies is still debated. The aim of this review is to highlight updates in the role of LT for certain malignancies, including HCC, metastatic CRC, hilar CCA, and neuroendocrine tumor (NET), as well as contextualize LT use and discuss controversies in transplant oncology.
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32
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Manzi J, Hoff CO, Ferreira R, Glehn-Ponsirenas R, Selvaggi G, Tekin A, O'Brien CB, Feun L, Vianna R, Abreu P. Cell-Free DNA as a Surveillance Tool for Hepatocellular Carcinoma Patients after Liver Transplant. Cancers (Basel) 2023; 15:3165. [PMID: 37370775 PMCID: PMC10296050 DOI: 10.3390/cancers15123165] [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: 05/02/2023] [Revised: 05/30/2023] [Accepted: 06/09/2023] [Indexed: 06/29/2023] Open
Abstract
The liver is the world's sixth most common primary tumor site, responsible for approximately 5% of all cancers and over 8% of cancer-related deaths. Hepatocellular carcinoma (HCC) is the predominant type of liver cancer, accounting for approximately 75% of all primary liver tumors. A major therapeutic tool for this disease is liver transplantation. Two of the most significant issues in treating HCC are tumor recurrence and graft rejection. Currently, the detection and monitoring of HCC recurrence and graft rejection mainly consist of imaging methods, tissue biopsies, and alpha-fetoprotein (AFP) follow-up. However, they have limited accuracy and precision. One of the many possible components of cfDNA is circulating tumor DNA (ctDNA), which is cfDNA derived from tumor cells. Another important component in transplantation is donor-derived cfDNA (dd-cfDNA), derived from donor tissue. All the components of cfDNA can be analyzed in blood samples as liquid biopsies. These can play a role in determining prognosis, tumor recurrence, and graft rejection, assisting in an overall manner in clinical decision-making in the treatment of HCC.
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Affiliation(s)
- Joao Manzi
- School of Medicine, University of Sao Paulo, Sao Paulo 05508-900, Brazil
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL 33136, USA
| | - Camilla O Hoff
- School of Medicine, University of Sao Paulo, Sao Paulo 05508-900, Brazil
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL 33136, USA
| | - Raphaella Ferreira
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL 33136, USA
| | | | - Gennaro Selvaggi
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL 33136, USA
| | - Akin Tekin
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL 33136, USA
| | - Christopher B O'Brien
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL 33136, USA
| | - Lynn Feun
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL 33136, USA
| | - Rodrigo Vianna
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL 33136, USA
| | - Phillipe Abreu
- Miami Transplant Institute, Jackson Memorial Hospital, University of Miami, Miami, FL 33136, USA
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Bosi C, Rimini M, Casadei-Gardini A. Understanding the causes of recurrent HCC after liver resection and radiofrequency ablation. Expert Rev Anticancer Ther 2023; 23:503-515. [PMID: 37060290 DOI: 10.1080/14737140.2023.2203387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/16/2023]
Abstract
INTRODUCTION Surgical resection and radiofrequency ablation are preferred options for early-stage disease, with 5-year recurrence rates as high as 70% when patients are treated according to guidelines. With increasing availability of therapeutic options, including but not limited to, immune-checkpoint inhibitors (ICI), tyrosine kinase inhibitors, antiangiogenics, and adoptive cell therapies, understanding the causes of recurrence and identifying its predictors should be priorities in the hepatocellular carcinoma (HCC) research agenda. AREAS COVERED Current knowledge of HCC predictors of recurrence is reviewed, and recent insights about its underlying mechanisms are presented. In addition, results from recent clinical trials investigating treatment combinations are critically appraised. EXPERT OPINION HCC recurrence is either due to progressive growth of microscopic residual disease, or to de novo cancer development in the context of a diseased liver, each occurring in an early (<2years) vs. late (≥2 years) fashion. Collectively, morphological, proteomic, and transcriptomic data suggest vascular invasion and angiogenesis as key drivers of HCC recurrence. Agents aimed at blocking either of these two hallmarks should be prioritized at the moment of early-stage HCC clinical trial design. Emerging results from clinical trials testing ICI in early-stage HCC underscore the importance of defining the best treatment sequence and the most appropriate combination strategies. Lastly, as different responses to systemic therapies are increasingly defined according to the HCC etiology, patient enrolment into clinical trials should take into account the biological characteristics of their inherent disease.
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Affiliation(s)
- Carlo Bosi
- Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
- Vita-Salute San Raffaele University School of Medicine, Milan, 20132, Italy
| | - Margherita Rimini
- Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
- Vita-Salute San Raffaele University School of Medicine, Milan, 20132, Italy
| | - Andrea Casadei-Gardini
- Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
- Vita-Salute San Raffaele University School of Medicine, Milan, 20132, Italy
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Ince V, Sahin TT, Akbulut S, Yilmaz S. Liver transplantation for hepatocellular carcinoma: Historical evolution of transplantation criteria. World J Clin Cases 2022; 10:10413-10427. [PMID: 36312504 PMCID: PMC9602233 DOI: 10.12998/wjcc.v10.i29.10413] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 07/27/2022] [Accepted: 08/25/2022] [Indexed: 02/05/2023] Open
Abstract
Liver transplantation (LT) for hepatocellular carcinoma is still a hot topic, and the main factor that is associated with the success of treatment is to determine the patients who will benefit from LT. Milan criteria have been defined 25 years ago and still is being used for patient selection for LT. However, in living donor LT, the Milan criteria is being extended. Current criteria for patient selection do not only consider morphologic characteristics such as tumor size and number of tumor nodules but also biologic markers that show tumor aggressiveness is also being considered. In the present review article, we have summarized all the criteria and scoring systems regarding LT for hepatocellular carcinoma. All criteria have 5-year overall survival rates that were comparable to the Milan Criteria and ranged between 60%-85%. On the other hand, it was seen that the recurrence rates had increased as the Milan criteria were exceeded; the 5-year recurrence rates ranged between 4.9% to 39.9%. Treatment of hepatocellular carcinoma needs a multidisciplinary approach. Ideal selection criteria are yet to be discovered. The same is true for treatment modalities. The goal will be achieved by a harmonic interplay between basic science researchers and clinicians.
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Affiliation(s)
- Volkan Ince
- Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya 44280, Turkey
| | - Tevfik Tolga Sahin
- Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya 44280, Turkey
| | - Sami Akbulut
- Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya 44280, Turkey
- Biostatistics and Medical Informatics, Inonu University Faculty of Medicine, Malatya 44280, Turkey
| | - Sezai Yilmaz
- Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya 44280, Turkey
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35
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Tran NH, Muñoz S, Thompson S, Hallemeier CL, Bruix J. Hepatocellular carcinoma downstaging for liver transplantation in the era of systemic combined therapy with anti-VEGF/TKI and immunotherapy. Hepatology 2022; 76:1203-1218. [PMID: 35765265 DOI: 10.1002/hep.32613] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 04/26/2022] [Accepted: 04/28/2022] [Indexed: 12/08/2022]
Abstract
Hepatocellular carcinoma remains a global health challenge affecting close to 1 million cases yearly. Liver transplantation provides the best long-term outcomes for those meeting strict criteria. Efforts have been made to expand these criteria, whereas others have attempted downstaging approaches. Although locoregional approaches to downstaging are appealing and have demonstrated efficacy, limitations and challenges exists including poor imaging modality to assess response and appropriate endpoints along the process. Recent advances in systemic treatments including immune checkpoint inhibitors alone or in combination with tyrosine kinase inhibitors have prompted the discussion regarding their role for downstaging disease prior to transplantation. Here, we provide a review of prior locoregional approaches for downstaging, new systemic agents and their role for downstaging, and finally, key and critical considerations of the assessment, endpoints, and optimal designs in clinical trials to address this key question.
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Affiliation(s)
- Nguyen H Tran
- Division of Medical OncologyDepartment of OncologyMayo ClinicRochesterMinnesotaUSA
| | - Sergio Muñoz
- BCLC GroupLiver UnitHospital Clinic BarcelonaIDIBAPSCIBEREHDUniversity of BarcelonaBarcelonaSpain
| | - Scott Thompson
- Division of Vascular and Interventional RadiologyDepartment of RadiologyMayo ClinicRochesterMinnesotaUSA
| | | | - Jordi Bruix
- BCLC GroupLiver UnitHospital Clinic BarcelonaIDIBAPSCIBEREHDUniversity of BarcelonaBarcelonaSpain
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36
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Tabrizian P, Holzner ML, Mehta N, Halazun K, Agopian VG, Yao F, Busuttil RW, Roberts J, Emond JC, Samstein B, Brown RS, Najjar M, Chapman WC, Doyle MM, Florman SS, Schwartz ME, Llovet JM. Ten-Year Outcomes of Liver Transplant and Downstaging for Hepatocellular Carcinoma. JAMA Surg 2022; 157:779-788. [PMID: 35857294 PMCID: PMC9301590 DOI: 10.1001/jamasurg.2022.2800] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
Importance National guidelines on transplant selection have adopted successful downstaging to within Milan criteria (MC) as a viable option for the treatment of hepatocellular carcinoma (HCC) before liver transplant (LT). Recurrence of HCC after LT carries a poor prognosis, and treatment modalities remain challenging. Objective To establish the 10-year outcomes of patients with HCC after LT in a large, multicenter US study based on individual data; provide robust data on the long-term role of downstaging; and evaluate the association of treatment modalities with postrecurrence survival. Design, Setting, and Participants In this cohort study, a retrospective, multicenter analysis of prospectively collected data was conducted for 2645 adults who had undergone LT for HCC at 5 US academic centers between January 2001 and December 2015. The analysis was performed from May 2019 through June 2021. Outcomes of 341 patients whose disease was downstaged to within MC were compared with those in 2122 patients whose disease was always within MC and 182 patients whose disease was not downstaged. The associations of tumor and treatment factors on postrecurrence survival were analyzed using Cox proportional hazards regression and multivariable logistic regression models. Main Outcomes and Measures The primary outcome was overall survival for the whole cohort and according to downstaging status. Secondary outcomes were time to recurrence, recurrence-free survival, and recurrence after specific post-LT therapies. Results Of the 2645 patients studied, the median age was 59.9 years (IQR, 54.7-64.7 years). The majority of the patients were men (2028 [76.7%] vs 617 [23.3%] women). The 10-year post-LT survival and recurrence rates were, respectively, 52.1% and 20.6% among those whose disease was downstaged; 61.5% and 13.3% in those always within MC; and 43.3% and 41.1% in those whose disease was not downstaged. Independent variables associated with downstaging failure were tumor size greater than 7 cm at diagnosis (OR, 2.62; 95% CI, 1.20-5.75; P = .02), more than 3 tumors at diagnosis (OR, 2.34; 95% CI, 1.22-4.50; P = .01), and α-fetoprotein response of at least 20 ng/mL with less than 50% improvement from maximum α-fetoprotein before LT (OR, 1.99; 95% CI, 1.14-3.46; P = .02). Surgically treated patients with recurrent HCC differed in clinicopathologic characteristics and had improved 5-year postrecurrence survival rates (31.6% vs 7.3%; P < .001). Conclusions and Relevance In a large, multicenter cohort of patients with HCC successfully downstaged to within MC, 10-year post-LT outcomes were excellent, validating national downstaging policies and showing a clear utility benefit for LT prioritization decision making. Surgical management of HCC recurrence after LT was associated with improved survival in well-selected patients and should be pursued, if feasible.
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Affiliation(s)
- Parissa Tabrizian
- Liver Transplant and Hepatobiliary Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Matthew L. Holzner
- Liver Transplant and Hepatobiliary Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Neil Mehta
- Division of Gastroenterology/Hepatology, Department of Medicine, University of California, San Francisco
| | - Karim Halazun
- Center for Liver Disease and Transplantation, Weill Cornell Medicine, New York, New York
| | - Vatche G. Agopian
- Division of Liver and Pancreas Transplantation, David Geffen School of Medicine, University of California, Los Angeles
| | - Francis Yao
- Division of Gastroenterology/Hepatology, Department of Medicine, University of California, San Francisco
| | - Ronald W. Busuttil
- Division of Liver and Pancreas Transplantation, David Geffen School of Medicine, University of California, Los Angeles
| | - John Roberts
- Division of Transplant Surgery, University of California, San Francisco
| | - Jean C. Emond
- Liver and Abdominal Transplant Surgery, Columbia University Irving Medical Center, New York, New York
| | - Benjamin Samstein
- Center for Liver Disease and Transplantation, Weill Cornell Medicine, New York, New York
| | - Robert S. Brown
- Center for Liver Disease and Transplantation, Weill Cornell Medicine, New York, New York
| | - Marc Najjar
- Liver and Abdominal Transplant Surgery, Columbia University Irving Medical Center, New York, New York
| | - William C. Chapman
- Section of Transplant Surgery, Division of General Surgery, Washington University School of Medicine in St Louis, Missouri
| | - Majella Mb. Doyle
- Section of Transplant Surgery, Division of General Surgery, Washington University School of Medicine in St Louis, Missouri
| | - Sander S. Florman
- Liver Transplant and Hepatobiliary Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Myron E. Schwartz
- Liver Transplant and Hepatobiliary Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Josep M. Llovet
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York
- Translational Research in Hepatic Oncology, Liver Unit, August Pi i Sunyer Biomedica Research Institute, Hospital Clinic, University of Barcelona, Catalonia, Spain
- Institució Catalana d’Estudis Avançats, Barcelona, Catalonia, Spain
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Stick to Milan: Infeasibility of the Brazil-Milan Criteria in recommending patients with hepatocellular carcinoma for liver transplantation. Ann Hepatol 2022; 25:100537. [PMID: 34547478 DOI: 10.1016/j.aohep.2021.100537] [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: 05/07/2021] [Accepted: 05/20/2021] [Indexed: 02/04/2023]
Abstract
This article discusses the infeasibility of adhering to the Brazil-Milan Criteria for determining whether patients with hepatocellular carcinoma (HCC) should be offered liver transplantation. The Criteria are currently used widely in Brazil. However, since they expand the net of the transplant-eligible population, and that transplantation is shown to improve clinical outcomes in HCC patients relative to other treatments, they are inherently attractive and may be adopted by other countries in determining whether HCC patients should receive liver transplantation. I argue that the Criteria unjustifiably disregard the number of tumour nodules found in the patient. This number may be indicative of the recurrence potential of the disease, since these nodules can originate from different clonal populations. The greater the number, the higher the risk these nodules are associated with clones which contain genetic mutations conferring even greater potential for proliferation and dissemination. Clusters of tumour cells may be micro-disseminated to vascular structures surrounding the liver, as well as extrahepatic systems. This increases recurrence potential and reduces the benefit of liver transplantation in these patients. Thus, HCC patients harbouring fewer but larger tumour nodules may present with a more favourable genomic and epigenomic profile than those with more, albeit smaller, tumour nodules. Patients with more tumour nodules may reap greater clinical benefit if initiated on systemic therapy early, rather than wait for a suitable donor liver. Although the Criteria are reached by consensus, with reference to findings from recent studies, as well as scientific theory, it is ripe for review.
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Tsou YF, Lin NC, Hsia CY, Loong CC, Tsai HL, Chen CY, Lei HJ, Chou SC, Chung MH, Kuo FC, Liu CS. Repeated loco-regional therapies for hepatocellular carcinoma is associated with inferior outcome after living donor liver transplantation in cirrhotic patients. J Chin Med Assoc 2022; 85:317-323. [PMID: 34812768 DOI: 10.1097/jcma.0000000000000670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Liver transplantation is the definitive treatment for defined stage hepatocellular carcinoma (HCC) in cirrhotic patients. Loco-regional therapy (LRT) may be considered before transplantation to prevent the disease progression and the patient from dropping out of the waiting list. This study aims to evaluate the impact of repeated pretransplant LRTs on the long-term outcomes in HCC liver transplant recipients. METHODS Between 2004 and 2019, living donor liver transplantation (LDLT) recipients with viable HCC on the explant livers were enrolled. Uni- and multivariate analysis was performed with the Cox regression model to stratify the risk factors associated with HCC recurrence and patent survival after LDLT. RESULTS A total of 124 patients were enrolled, in which 65.3% (n = 81) were Barcelona Clinic Liver Cancer classification stage B or D and 89% (n = 110) had advanced fibrosis or cirrhosis on the explanted livers. After a median follow-up of 41 months (IQR: 24-86.5), there were 18 cases (13.7%) of HCC recurrence. Univariate analysis showed that the model of end-stage liver disease and Child-Turcotte-Pugh score, pretransplant alpha-fetoprotein value (>500 ng/ml), repeated pretransplant LRTs (N > 4), increased tumor numbers and maximal size, presence of microvascular invasion, and the histological grading of the tumors are risk factors of inferior outcomes. In multivariate analysis, only repeated pretransplant LRTs (N > 4) had a significant impact on both the overall- and recurrence-free survival. The impact of pretransplant LRT was consistently significant among subgroups based on their LRT episodes (N = 0, 1-4, >4 respectively). CONCLUSION Repeated LRT for HCC can be associated with the risk of tumor recurrence and inferior patient survival after LDLT in cirrhotic patients. Early referral of those eligible for transplantation may improve the treatment outcomes in these patients.
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Affiliation(s)
- Yi-Fan Tsou
- Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Niang-Cheng Lin
- Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Cheng-Yuan Hsia
- Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Che-Chuan Loong
- Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Hsin-Lin Tsai
- Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Division of Pediatric Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Cheng-Yen Chen
- Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Hao-Jan Lei
- Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Shu-Cheng Chou
- Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Meng-Hsuan Chung
- Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Fang-Cheng Kuo
- Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Chin-Su Liu
- Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Division of Pediatric Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
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Tan DJH, Lim WH, Yong JN, Ng CH, Muthiah MD, Tan EX, Xiao J, Lim SY, Pin Tang AS, Pan XH, Kabir T, Bonney GK, Sundar R, Syn N, Kim BK, Dan YY, Noureddin M, Loomba R, Huang DQ. UNOS Down-Staging Criteria for Liver Transplantation of Hepatocellular Carcinoma: Systematic Review and Meta-Analysis of 25 Studies. Clin Gastroenterol Hepatol 2022; 21:1475-1484. [PMID: 35181565 DOI: 10.1016/j.cgh.2022.02.018] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 02/03/2022] [Accepted: 02/07/2022] [Indexed: 01/11/2023]
Abstract
BACKGROUND & AIMS Down-staging is commonly used to select patients with hepatocellular carcinoma (HCC) beyond Milan criteria (MC) for liver transplantation (LT), but outcomes are heterogenous. We aimed to estimate pooled down-staging success rates, HCC recurrence, and overall survival (OS), stratified by criteria used for baseline tumor burden. METHODS We searched Pubmed and EMBASE databases from inception until August 2021 for studies reporting down-staging success (reduction of tumor burden to within MC) and outcomes of adult HCC patients. In addition, we performed a pooled analysis using reconstructed individual participant data to obtain robust estimates for OS. RESULTS We screened 1059 articles and included 25 articles involving 3997 patients. Overall, 55.16% (45.49%-64.46%) underwent successful down-staging, and 31.52% (24.03%-40.11%) received LT (by intention-to-treat analysis [ITT]). Among patients who received LT, 16.01% (11.80%-21.37%) developed HCC recurrence. Comparing studies that used the United Network for Organ Sharing Down-Staging (UNOS-DS) criteria versus studies beyond UNOS-DS or did not specify criteria, down-staging success (by ITT) was 83.21% versus 45.93%, P < .001; the proportion who received LT (by ITT) was 48.61% vs 28.60%, P = .030; and HCC recurrence (among patients who received LT) occurred in 9.06% versus 20.42%, P < .001. Among studies that used UNOS-DS criteria, ITT 1- and 5-year OS from the initiation of down-staging treatment was 86% and 58%, respectively, whereas 1- and 5-year post-LT OS was 94% and 74%, respectively. CONCLUSIONS Among studies that adhered to UNOS-DS criteria, down-staging was successful in four-fifths of patients, >50% received LT, and post-LT outcomes were excellent. These data provide clinical validation for the utilization of UNOS-DS criteria.
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Affiliation(s)
- Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jie Ning Yong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Eunice X Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Jieling Xiao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Snow Yunni Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Ansel Shao Pin Tang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Xin Hui Pan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Tousif Kabir
- Department of General Surgery, Sengkang General Hospital, Singapore; Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Glenn K Bonney
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, National University Hospital, National University Health System, Singapore, Singapore
| | - Raghav Sundar
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Department of Haematology-Oncology, National University Cancer Institute, Singapore
| | - Nicholas Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Biostatistics and Modelling Domain, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Yock Young Dan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore; Biostatistics and Modelling Domain, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore
| | - Mazen Noureddin
- Cedars-Sinai Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Rohit Loomba
- NAFLD Research Center, Division of Medicine, University of California San Diego, La Jolla, California
| | - Daniel Q Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore; NAFLD Research Center, Division of Medicine, University of California San Diego, La Jolla, California.
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Reddy T, Esmail A, Chang JC, Ghobrial RM, Abdelrahim M. Utility of Cell-Free DNA Detection in Transplant Oncology. Cancers (Basel) 2022; 14:cancers14030743. [PMID: 35159010 PMCID: PMC8833373 DOI: 10.3390/cancers14030743] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 01/20/2022] [Accepted: 01/29/2022] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Transplant oncology is an emerging field in cancer treatment that applies transplant medicine, surgery, and oncology to improve cancer patient survival and quality of life. This review aims to provide a comprehensive overview of the history and emergence of cfDNA technology, its applications to specifically monitor tumor burden at pre-and post-liver transplant stages, and evaluate transplant rejection. The use of ctDNA to evaluate transplant rejection has been extensively studied in non-hepatocellular carcinoma (HCC) diseases. Emerging studies have also investigated the use of ctDNA detection in evaluating HCC tumor burden pre-and post-surgery as well as transplant rejection. However, extensive studies still need to be conducted to evaluate the role of ctDNA detection in the medical management of transplant oncology patients. Abstract Transplant oncology is an emerging field in cancer treatment that applies transplant medicine, surgery, and oncology to improve cancer patient survival and quality of life. A critical concept that must be addressed to ensure the successful application of transplant oncology to patient care is efficient monitoring of tumor burden pre-and post-transplant and transplant rejection. Cell-free DNA (cfDNA) detection has emerged as a vital tool in revolutionizing the management of cancer patients who undergo organ transplantation. The advances in cfDNA technology have provided options to perform a pre-transplant evaluation of minimal residual disease (MRD) and post-transplant evaluation of cancer recurrence and transplant rejection. This review aims to provide a comprehensive overview of the history and emergence of cfDNA technology, its applications to specifically monitor tumor burden at pre-and post-transplant stages, and evaluate transplant rejection.
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Affiliation(s)
- Tejaswini Reddy
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (T.R.); (A.E.)
- Texas A&M Health Science Center, College of Medicine, Bryan, TX 77807, USA
- Houston Methodist Research Institute, Houston, TX 77030, USA;
| | - Abdullah Esmail
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (T.R.); (A.E.)
- Houston Methodist Research Institute, Houston, TX 77030, USA;
| | - Jenny C. Chang
- Houston Methodist Research Institute, Houston, TX 77030, USA;
- Section of Breast, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA
| | - Rafik Mark Ghobrial
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA;
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr Center for Transplantation, Houston, TX 77030, USA
| | - Maen Abdelrahim
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (T.R.); (A.E.)
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA;
- Cockrell Center of Advanced Therapeutics Phase I program, Houston Methodist Research Institute, Houston, TX 77030, USA
- Correspondence:
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Role of Pretransplant Treatments for Patients with Hepatocellular Carcinoma Waiting for Liver Transplantation. Cancers (Basel) 2022; 14:cancers14020396. [PMID: 35053558 PMCID: PMC8773674 DOI: 10.3390/cancers14020396] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/09/2022] [Accepted: 01/12/2022] [Indexed: 02/01/2023] Open
Abstract
Simple Summary Hepatocellular carcinoma (HCC) is the fifth most common cancer in men worldwide and the second leading cause of cancer death. Liver transplantation (LT) is one of the treatment options for patients with HCC. Recently, there have been many reports of the usefulness of locoregional therapy, such as transarterial chemoembolization and radiofrequency ablation, for HCC as pretreatment before LT. In Western countries, locoregional therapy is used to bridge until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. With the progress of locoregional therapy, new reports on the effects of bridging and downstaging locoregional therapy as pretransplant treatment are increasing in number. Abstract Recently, there have been many reports of the usefulness of locoregional therapy such as transarterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma (HCC) as pretreatment before liver transplantation (LT). Locoregional therapy is performed with curative intent in Japan, where living donor LT constitutes the majority of LT due to the critical shortage of deceased donors. However, in Western countries, where deceased donor LT is the main procedure, LT is indicated for early-stage HCC regardless of liver functional reserve, and locoregional therapy is used for bridging until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. There are many reports of the effect of bridging and downstaging locoregional therapy before LT, and its indications and efficacy are becoming clear. Responses to locoregional therapy, such as changes in tumor markers, the avidity of FDG-PET, etc., are considered useful for successful bridging and downstaging. In this review, the effects of bridging and downstaging locoregional therapy as a pretransplant treatment on the results of transplantation are clarified, focusing on recent reports.
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Gao Q, Anwar IJ, Abraham N, Barbas AS. Liver Transplantation for Hepatocellular Carcinoma after Downstaging or Bridging Therapy with Immune Checkpoint Inhibitors. Cancers (Basel) 2021; 13:6307. [PMID: 34944927 PMCID: PMC8699137 DOI: 10.3390/cancers13246307] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Revised: 12/13/2021] [Accepted: 12/14/2021] [Indexed: 12/12/2022] Open
Abstract
Liver transplantation offers excellent outcomes for patients with HCC. For those who initially present within the Milan criteria, bridging therapy is essential to control disease while awaiting liver transplant. For those who present beyond the Milan criteria, a liver transplant may still be considered following successful downstaging. Since the introduction of atezolizumab as part of the first-line treatment for HCC in 2020, there has been increasing interest in the use of ICIs as bridging or downstaging therapies prior to liver transplant. A total of six case reports/series have been published on this topic, with mixed outcomes. Overall, liver transplantation can be performed safely following prolonged ICI use, though ICIs may increase the risk of fulminant acute rejection early in the post-operative period. A minimal washout period between the last dose of ICI and liver transplantation has been identified as an important factor predicting transplant outcomes; however, further research is needed.
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Affiliation(s)
| | | | | | - Andrew S. Barbas
- Department of Surgery, Duke University Medical Center, Durham, NC 27705, USA; (Q.G.); (I.J.A.); (N.A.)
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Nakamura T, Shirouzu T. Antibody-Mediated Rejection and Recurrent Primary Disease: Two Main Obstacles in Abdominal Kidney, Liver, and Pancreas Transplants. J Clin Med 2021; 10:5417. [PMID: 34830699 PMCID: PMC8619797 DOI: 10.3390/jcm10225417] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 11/17/2021] [Accepted: 11/18/2021] [Indexed: 02/08/2023] Open
Abstract
The advances in acute phase care have firmly established the practice of organ transplantation in the last several decades. Then, the next issues that loom large in the field of transplantation include antibody-mediated rejection (ABMR) and recurrent primary disease. Acute ABMR is a daunting hurdle in the performance of organ transplantation. The recent progress in desensitization and preoperative monitoring of donor-specific antibodies enables us to increase positive outcomes. However, chronic active ABMR is one of the most significant problems we currently face. On the other hand, recurrent primary disease is problematic for many recipients. Notably, some recipients, unfortunately, lost their vital organs due to this recurrence. Although some progress has been achieved in these two areas, many other factors remain largely obscure. In this review, these two topics will be discussed in light of recent discoveries.
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Affiliation(s)
- Tsukasa Nakamura
- Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kajii-cho 465, Kamigyo-ku, Kyoto 602-8566, Japan
| | - Takayuki Shirouzu
- Molecular Diagnositcs Division, Wakunaga Pharmaceutical Co., Ltd., 13-4 Arakicho, shinjyuku-ku, Tokyo 160-0007, Japan;
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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: 9] [Impact Index Per Article: 2.3] [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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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: 8] [Impact Index Per Article: 2.0] [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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Bhatti ABH, Naqvi W, Khan NY, Zia HH, Dar FS, Khan ZA, Rana A. Living donor liver transplantation for advanced hepatocellular carcinoma including macrovascular invasion. J Cancer Res Clin Oncol 2021; 148:245-253. [PMID: 34117916 PMCID: PMC8752562 DOI: 10.1007/s00432-021-03665-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 05/13/2021] [Indexed: 02/05/2023]
Abstract
Background The indications for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) continue to evolve. The aim of this study was to report outcomes in patients who underwent living donor liver transplantation (LDLT) for HCC outside traditional criteria including macrovascular invasion (MVI). Methods We reviewed outcomes in patients who met the University of California San Francisco (UCSF) criteria (n = 159) and our center-specific criteria (UCSF+) (largest tumor diameter ≤ 10 cm, any tumor number, AFP ≤ 1000 ng/ml) (n = 58). We also assessed outcomes in patients with MVI (n = 27). Results The median follow was 28 (10.6–42.7) months. The 5 year overall survival and risk of recurrence (RR) in the UCSF and UCSF + group was 71% vs 69% (P = 0.7) and 13% vs 36% (P = 0.1) respectively. When patients with AFP > 600 ng/ml were excluded from the UCSF + group, RR was 27% (P = 0.3). Among patients with MVI who had downstaging (DS), 4/5(80%) in low-risk group (good response and AFP ≤ 100 ng/ml) and 2/10 (20%) in the high-risk group (poor response or AFP > 100 ng/ml) were alive at the last follow-up. When DS was not feasible, 3/3 (100%) in the low-risk group (AFP ≤ 100 ng/ml + Vp1-2 MVI) and 1/9 (9.1%) in the high-risk group (AFP > 100 or Vp3 MVI) were alive. The 5 year OS in the low-risk MVI group was 85% (P = 0.003). Conclusion With inclusion of AFP, response to downstaging and degree of MVI, acceptable survival can be achieved with LDLT for HCC outside traditional criteria. Supplementary Information The online version contains supplementary material available at 10.1007/s00432-021-03665-9.
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Affiliation(s)
- Abu Bakar Hafeez Bhatti
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Sector H-8/4, Pitras Bukhari Road, Islamabad, 44000, Pakistan. .,Department of Surgery, Shifa Tameer-e-Millat University Islamabad, Islamabad, Pakistan.
| | - Wajih Naqvi
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Sector H-8/4, Pitras Bukhari Road, Islamabad, 44000, Pakistan
| | - Nusrat Yar Khan
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Sector H-8/4, Pitras Bukhari Road, Islamabad, 44000, Pakistan
| | - Haseeb Haider Zia
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Sector H-8/4, Pitras Bukhari Road, Islamabad, 44000, Pakistan
| | - Faisal Saud Dar
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Sector H-8/4, Pitras Bukhari Road, Islamabad, 44000, Pakistan
| | - Zahid Amin Khan
- Division of Radiology, Shifa International Hospital Islamabad, Islamabad, Pakistan
| | - Atif Rana
- Division of Radiology, Shifa International Hospital Islamabad, Islamabad, Pakistan
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Panayotova G, Lunsford KE, Latt NL, Paterno F, Guarrera JV, Pyrsopoulos N. Expanding indications for liver transplantation in the era of liver transplant oncology. World J Gastrointest Surg 2021; 13:392-405. [PMID: 34122730 PMCID: PMC8167850 DOI: 10.4240/wjgs.v13.i5.392] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 02/23/2021] [Accepted: 05/07/2021] [Indexed: 02/06/2023] Open
Abstract
Despite numerous advances and emerging data, liver transplantation in the setting of gastrointestinal malignancies remains controversial outside of certain accepted indications. In an era of persistent organ shortage and increasing organ demand, allocation of liver grafts must be considered carefully. While hepatocellular carcinoma and hilar cholangiocarcinoma have become accepted indications for transplantation, tumor size and standardized multi-disciplinary treatment protocols are necessary to ensure optimal patient outcomes. As more studies seeking to expand the oncologic indications for liver transplantation are emerging, it is becoming increasingly clear that tumor biology and response to therapy are key factors for optimal oncologic outcomes. In addition, time from diagnosis to transplantation appears to correlate with survival, as stable disease over time portends better outcomes post-operatively. Identifying aggressive disease pre-transplant remains difficult with current imaging and tissue sampling techniques. While tumor size and stage are important prognostic predictors for most malignancies, patient and tumor selection protocols are necessary. As the fields of medical and surgical oncology continue to evolve, it is clear that a protocolized interdisciplinary treatment approach is necessary for combatting any cancer effectively. Disease stability over time and response to neoadjuvant therapy may be the best predictors for successful patient outcomes and can be easily incorporated in our treatment paradigms. Current data evaluating liver transplantation for expanded oncologic indications such as: expanded criteria hepatocellular carcinoma, intrahepatic cholangiocarcinoma, mixed tumors, and liver limited metastatic colorectal carcinomas, incorporate multi-modal therapies and evaluation of tumor treatment response. While further investigation is necessary, initial results suggest there is an expanded role for transplant surgery in malignancy in a new era of liver transplant oncology.
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Affiliation(s)
- Guergana Panayotova
- Division of Transplant and Hepatobiliary Surgery, Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Keri E Lunsford
- Division of Transplant and Hepatobiliary Surgery, Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
- Center for Immunity and Inflammation, Institute for Infectious and Inflammatory Diseases, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Nyan L Latt
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Flavio Paterno
- Division of Transplant and Hepatobiliary Surgery, Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - James V Guarrera
- Division of Transplant and Hepatobiliary Surgery, Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Nikolaos Pyrsopoulos
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
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The Matching Status Between Donor and Recipient Hepatitis B Seroepidemiology Makes a Difference in Liver Transplantation for Hepatocellular Carcinoma. Clin Transl Gastroenterol 2021; 11:e00168. [PMID: 32358239 PMCID: PMC7263649 DOI: 10.14309/ctg.0000000000000168] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Antibody to hepatitis B core antigen (HBcAb) is known to be related with the prognosis for patients with hepatocellular carcinoma (HCC). This study aims to evaluate the prognostic capacity of HbcAb and other donor/recipient hepatitis B seroepidemiological indexes in transplantation for HCC.
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Abstract
PURPOSE HCC is a complex disease that is diagnosed in advanced stage and on the background of cirrhosis. Locoregional therapies provide sufficient downstaging to enable patients suitable for radical procedures such liver transplantation. However, the interval between locoregional therapies and definitive therapy is still controversial. We performed a review of literature to evaluate the role of waiting period between locoregional therapies and liver transplantation or resection from the perspective of cure and recurrence rates. METHODS Thorough literature search was performed to evaluate the role of locoregional therapy and the interval to definitive therapies for the treatment of hepatocellular cancer. RESULTS Usually, small tumors with lower tumor burden, in other words, tumors within Milan criteria, can be transplanted with an acceptable overall and disease-free survival. However, treating patients with locally advanced tumors is currently a matter of extensive research. Currently, locoregional therapies are applied to downstage the patients. However, the duration of waiting is a crucial point that needs further research. There is a consensus that the waiting interval between down-staging and transplantation should be no less than 3 months. This is important for selection of favorable tumor biology as well as from the point of antitumor immune response. CONCLUSION Currently, there are no surrogate markers for surveillance of response to locoregional therapies as well as the antitumor immune response that develops as a result of down-staging.
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50
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Isik B, Gonultas F, Sahin T, Yilmaz S. Microvascular Venous Invasion in Hepatocellular Carcinoma: Why Do Recurrences Occur? J Gastrointest Cancer 2021; 51:1133-1136. [PMID: 32839943 DOI: 10.1007/s12029-020-00487-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE Hepatocellular carcinoma is the most common primary cancer of the liver. It is almost always associated with cirrhosis and it is usually diagnosed in later stages of the disease. Furthermore, recurrence rate following liver transplantation ranges between 15 and 30%. The most important factor determining the recurrence is vascular invasion. METHODS In this review, the issue of microvascular invasion causing hepatocellular carcinoma recurrence is reviewed. Macroscopic vascular invasion is almost easy to diagnose on radiologic evaluation. However, microscopic vascular invasion is almost always diagnosed with pathologic evaluation. On the other hand, microscopic vascular invasion is associated with early recurrences and reduced disease-free survival. The type of vessel that is invaded determines the nature of the spread of the tumor cells. Invasion of the hepatic venous tributaries leads to systemic metastasis whereas portal venous invasions lead to intrahepatic spread of the tumor. Microscopic vascular invasion should be diagnosed before liver transplantation or liver resection in order to deliver the appropriate therapy to the patients. RESULTS Yet, there is no ideal marker to suggest microscopic vascular invasion before any intervention. Markers such as alpha-fetoprotein, des carboxy prothrombin, or gamma-glutamyl transferase have been found to be correlated with microscopic vascular invasion. These parameters are not very efficient to be used in routine clinical practice. CONCLUSION Therefore, further research is needed to define ideal marker associated with microscopic vascular invasion.
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Affiliation(s)
- Burak Isik
- Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, 244280, Malatya, Turkey
| | - Fatih Gonultas
- Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, 244280, Malatya, Turkey
| | - Tolga Sahin
- Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, 244280, Malatya, Turkey
| | - Sezai Yilmaz
- Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, 244280, Malatya, Turkey. .,Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Elazig Yolu 10. Km, 44280, Malatya, Turkey.
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