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Singh A, Singh C, Dhaliwal A, Singh N, Kumar V, Sohal A, Schneider J. Incidence, screening, and management of de novo malignancies in liver transplant patients: A review. World J Transplant 2025; 15:101046. [DOI: 10.5500/wjt.v15.i3.101046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 01/29/2025] [Accepted: 02/27/2025] [Indexed: 04/18/2025] Open
Abstract
Liver transplantation (LT) is the definitive treatment for end-stage liver disease, acute liver failure, and liver cancer. Although advancements in surgical techniques, postoperative care, and immunosuppressive therapies have significantly improved outcomes, the long-term use of immunosuppression has increased the risk of complications, including infections, cardiovascular disease, and cancer. Among these, de novo malignancies (DNMs) are a major concern, accounting for 20%-25% of deaths in LT recipients surviving beyond the early post-transplant period. Non-melanoma skin cancers, particularly squamous cell carcinoma are the most prevalent DNMs. Other significant malignancies include Kaposi's sarcoma, post-transplant lymphoproliferative disorders, and various solid organ cancers, including head and neck cancers. Compared to the general population, LT patients face a twofold increase in solid organ malignancies and a 30-fold increase in lymphoproliferative disorders. Risk factors for DNM include chronic immunosuppression, alcohol or tobacco use, viral infections, and underlying liver disease. Emerging evidence emphasizes the importance of tailored cancer screening and prevention strategies, including regular dermatological examinations, targeted screenings for high-risk cancers, and patient education on lifestyle modifications. Early detection through enhanced surveillance protocols has been shown to improve outcomes. Management of DNMs involves a combination of standard oncological therapies and adjustments to immunosuppressive regimens, with promising results from the use of mTOR inhibitors in select patients. The review highlights the critical need for ongoing research to refine risk stratification, optimize screening protocols, and improve treatment approaches to mitigate the burden of DNMs in LT recipients. By implementing personalized preventive and therapeutic strategies, we can enhance long-term outcomes and quality of life for this vulnerable population.
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Affiliation(s)
- Anmol Singh
- Department of Medicine, Tristar Centennial Medical Center, Nashville, TN 37203, United States
| | - Carol Singh
- Department of Medicine, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India
| | - Armaan Dhaliwal
- Division of Hematology and Oncology, Lehigh Valley Health Network, Allentown, PA 18103, United States
| | - Navdeep Singh
- Department of Medicine, Government Medical College, Amritsar 143001, Punjab, India
| | - Vikash Kumar
- Division of Gastroenterology, Creighton University School of Medicine, Phoenix, AZ 85012, United States
| | - Aalam Sohal
- Division of Gastroenterology, Creighton University School of Medicine, Phoenix, AZ 85012, United States
| | - Jonathan Schneider
- Division of Gastroenterology, Tristar Centennial Medical Center, Nashville, TN 37203, United States
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Xu X, Zhang S, Luo Z, Zheng Y, Kong T, Huang C, Qiu Z. Frontiers and Controversies in De Novo Gastrointestinal Tumors After Organ Transplantation: Current Progress and Future Directions. Ann Surg Oncol 2025; 32:3392-3405. [PMID: 40035907 DOI: 10.1245/s10434-025-16975-w] [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: 11/06/2024] [Accepted: 01/21/2025] [Indexed: 03/06/2025]
Abstract
The increasing success of organ transplantation has significantly improved survival for patients with end-stage diseases, yet it introduces a complex dilemma: the elevated risk for the development of de novo gastrointestinal (GI) tumors. The sustained immunosuppression required to maintain graft function paradoxically undermines the body's natural defenses against cancer, leading to a higher incidence, aggressive progression, and atypical presentations of GI tumors among transplant recipients compared with the general population. This presents a pressing challenge: balancing the dual imperatives of preventing graft rejection and effectively managing malignancies. Current treatment paradigms, including surgical approaches, chemotherapy, radiation therapy, and the emerging role of immunotherapy, are fraught with complexities due to the altered immune landscape in these patients. This review underscores the critical need to understand the multifaceted relationship between post-transplantation immunosuppression and tumorigenesis, providing a comprehensive exploration of epidemiologic shifts, pathophysiologic insights, and the intricacies of the tumor microenvironment in this unique patient population. Understanding and managing GI tumors in transplant recipients is not only a clinical challenge, but also a necessary frontier in transplant oncology, promising to refine therapeutic strategies and improve the longevity and quality of life for this growing patient cohort.
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Affiliation(s)
- Ximo Xu
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shaopeng Zhang
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zai Luo
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yan Zheng
- Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tingting Kong
- Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chen Huang
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Zhengjun Qiu
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Gabrielli F, Bernasconi E, Toscano A, Avossa A, Cavicchioli A, Andreone P, Gitto S. Side Effects of Immunosuppressant Drugs After Liver Transplant. Pharmaceuticals (Basel) 2025; 18:342. [PMID: 40143120 PMCID: PMC11946649 DOI: 10.3390/ph18030342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 02/18/2025] [Accepted: 02/26/2025] [Indexed: 03/28/2025] Open
Abstract
Liver transplantation (LT) is the standard of care for both end-stage liver failure and hepatocellular carcinoma (HCC). Side effects of the main used immunosuppressive drugs have a noteworthy impact on the long-term outcome of LT recipients. Consequently, to achieve a balance between optimal immunosuppression and minimal side effects is a cornerstone of the post-LT period. Today, there are no validated markers for overimmunosuppression and underimmunosuppression, only a few drugs have therapeutic drug monitoring, and immunosuppression regimens vary from center to center and from country to country. Currently, there are many drugs with different efficacy and safety profiles. Using different agents permits a decrease in the dosage and minimizes the toxicities. A small subset of recipients achieves immunotolerance with the chance to stop immunosuppressive therapy. This article focuses on the side effects of immunosuppressive drugs, which significantly impact long-term outcomes for LT recipients. The primary aim is to highlight the balance between achieving effective immunosuppression and minimizing adverse effects, emphasizing the role of personalized therapeutic strategies. Moreover, this review evaluates the mechanisms of action and specific complications associated with immunosuppressive agents. Finally, special attention is given to strategies for reducing immunosuppressive burdens, improving patient quality of life, and identifying immunotolerant individuals.
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Affiliation(s)
- Filippo Gabrielli
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU of Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Elisa Bernasconi
- Postgraduate School of Internal Medicine, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Arianna Toscano
- Division of Internal Medicine, University Hospital of Policlinico G. Martino, 98124 Messina, Italy
| | - Alessandra Avossa
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Alessia Cavicchioli
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU of Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Pietro Andreone
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU of Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
- Postgraduate School of Allergology and Clinical Immunology, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Stefano Gitto
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
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Balzano E, Bernardi L, Candita G, Trizzino A, Petagna L, Bozzi E, Scalise P, Cristaudi A, Tincani G, Pezzati D, Ghinolfi D, Crocetti L. Transabdominal Robotic-Assisted Partial Nephrectomy and CT-Guided Percutaneous Cryoablation for the Treatment of De Novo Kidney Tumors After Liver Transplantation. Life (Basel) 2025; 15:254. [PMID: 40003663 PMCID: PMC11856640 DOI: 10.3390/life15020254] [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: 01/08/2025] [Revised: 01/29/2025] [Accepted: 02/04/2025] [Indexed: 02/27/2025] Open
Abstract
The management of de novo kidney tumors (DKTs) after liver transplantation (LT) is challenging due to previous transplant surgery and calcineurin inhibitors (CNI)-related nephrotoxicity. Minimally invasive renal-sparing strategies like robot-assisted partial nephrectomy (RPN) are favored, but a transperitoneal approach may be limited by the previous transplant surgery and the location of the DKT; in such cases, CT-guided cryoablation may be an alternative option. In this retrospective cohort study, we aimed to compare RPN and cryoablation for the treatment of DKT in LT recipients. The primary endpoints were the efficacy (R0 resection in RPN, absence of the tumor at first follow-up for cryoablation) and the safety of the procedures (postoperative morbidity and increase in creatine level). The periprocedural costs and the oncologic efficacy (recurrence and overall survival) were the secondary endpoints. Twelve LT recipients (91.7% males, mean age 65 years) underwent RPN (n = 6) or cryoablation (n = 6) for DKT; the median interval between LT and diagnosis of DKT was 142.5 vs. 117.5 months, respectively. Efficacy was obtained in all patients after RPN and cryoablation. Postoperative morbidity was 16.7% in each group, and the postoperative increase in creatinine values was similar. Hospital stay was shorter following cryoablation vs. RPN (3.1 vs. 6.7 days; p = 0.03). The mean procedural costs were higher for RPN. There was no mortality and none of the patients had signs of recurrence after a median follow-up of 40.5 months. Both RPN and CT-guided cryoablation were safe and effective for the treatment of selected patients with DKT after LT. When applicable, cryoablation may be cost-effective and provide faster recovery.
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Affiliation(s)
- Emanuele Balzano
- Hepatobiliary Surgery and Liver Transplant Division, Azienda Ospedaliero Universitaria Pisana (AOUP), University of Pisa, 56126 Pisa, Italy; (A.T.); (L.P.); (D.G.)
| | - Lorenzo Bernardi
- Department of Surgery, Lugano Regional Hospital, Ente Ospedaliero Cantonale (EOC), 6900 Lugano, Switzerland; (L.B.)
- Faculty of Biology and Medicine, University of Lausanne (UNIL), 1015 Lausanne, Switzerland
| | - Gianvito Candita
- Interventional Radiology Division, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy (E.B.); (P.S.); (L.C.)
| | - Arianna Trizzino
- Hepatobiliary Surgery and Liver Transplant Division, Azienda Ospedaliero Universitaria Pisana (AOUP), University of Pisa, 56126 Pisa, Italy; (A.T.); (L.P.); (D.G.)
| | - Lorenzo Petagna
- Hepatobiliary Surgery and Liver Transplant Division, Azienda Ospedaliero Universitaria Pisana (AOUP), University of Pisa, 56126 Pisa, Italy; (A.T.); (L.P.); (D.G.)
| | - Elena Bozzi
- Interventional Radiology Division, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy (E.B.); (P.S.); (L.C.)
| | - Paola Scalise
- Interventional Radiology Division, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy (E.B.); (P.S.); (L.C.)
| | - Alessandra Cristaudi
- Department of Surgery, Lugano Regional Hospital, Ente Ospedaliero Cantonale (EOC), 6900 Lugano, Switzerland; (L.B.)
| | - Giovanni Tincani
- Hepatobiliary Surgery and Liver Transplant Division, Azienda Ospedaliero Universitaria Pisana (AOUP), University of Pisa, 56126 Pisa, Italy; (A.T.); (L.P.); (D.G.)
| | - Daniele Pezzati
- Hepatobiliary Surgery and Liver Transplant Division, Azienda Ospedaliero Universitaria Pisana (AOUP), University of Pisa, 56126 Pisa, Italy; (A.T.); (L.P.); (D.G.)
| | - Davide Ghinolfi
- Hepatobiliary Surgery and Liver Transplant Division, Azienda Ospedaliero Universitaria Pisana (AOUP), University of Pisa, 56126 Pisa, Italy; (A.T.); (L.P.); (D.G.)
| | - Laura Crocetti
- Interventional Radiology Division, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy (E.B.); (P.S.); (L.C.)
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy
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Briant AR, Morello R, Sérée O, Vigneron N, Wilson S, Besch C, Houssel-Debry P, Pageaux GP, Coilly A, Dumortier J, Altieri M. Is Survival Impacted by One or Several Successive Cancers After Liver Transplantation? A French National Study. Clin Transplant 2025; 39:e70109. [PMID: 39945212 DOI: 10.1111/ctr.70109] [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: 07/25/2024] [Revised: 10/09/2024] [Accepted: 02/02/2025] [Indexed: 05/09/2025]
Abstract
BACKGROUND AND AIM De novo cancers after liver transplantation (LT) are major causes of complications and mortality after LT. No report was found in the literature on several successive cancers (SSC). The aim of this study was to see if the survival of one or more cancers was different and to study the survival prognostic factors of patients with one cancer or SSC after LT. METHODS Using data from the French national database, 114 French patients who underwent LT between 1993 and 2012 were followed up until their death or until June 2016. The Cox model performed to analyze potential risk factors (cancer characteristics, immunosuppressive therapy (IT), smoking, and alcohol use). RESULTS After an average follow-up of 9.8 ± 5.1 years, 52 patients developed 1 cancer, 49 had 2 cancers, and 13 had 3 cancers. The reduction in survival time was significantly and independently associated with the metastatic stage (hazard ratio (HR) = 3.98, 95% confidence interval (95% CI) = [1.45-10.93], p < 0.001), ENT (otolaryngology), and respiratory cancer versus genitourinary (HR = 8.28, 95% CI = [3.12-22.02], p < 0.001), and SSC (HR = 2.54, 95% CI = [1.39-4.65], p = 0.014). CONCLUSION The patients with ENT, respiratory cancers have a shorter survival. The stage of cancer and SSC reduces median survival at 10 years. The earliness of the first cancer should be taken as a warning signal of risk of SSC and impaired survival.
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Affiliation(s)
- Anaïs R Briant
- Normandie Univ, UNICAEN, CHU de Caen Normandie, Research and Innovation Department and Methodology Platform, Biostatistics and Clinical Research Units, Caen, France
- OncoNormandie, DSRC, Caen, France
| | - Rémy Morello
- Normandie Univ, UNICAEN, CHU de Caen Normandie, Research and Innovation Department and Methodology Platform, Biostatistics and Clinical Research Units, Caen, France
| | | | - Nicolas Vigneron
- Normandie Univ, UNICAEN, CHU de Caen Normandie, Research and Innovation Department and Methodology Platform, Biostatistics and Clinical Research Units, Caen, France
- Unicancer, Comprehensive Cancer Center F. Baclesse, Calvados General Tumor Registry, Caen, France
- UFR Santé Caen France: U1086 INSERM- "ANTICIPE", Caen, France
| | - Sarah Wilson
- Normandie Univ, UNICAEN, CHU de Caen Normandie, Research and Innovation Department and Methodology Platform, Biostatistics and Clinical Research Units, Caen, France
- UFR Santé Caen France: U1086 INSERM- "ANTICIPE", Caen, France
| | - Camille Besch
- Service de chirurgie hépato-bilio-pancréatique et transplantation hépatique, CHRU Hautepierre, Strasbourg, France
| | - Pauline Houssel-Debry
- Hôpital Universitaire de Pontchaillou, Service d'Hépatologie et Transplantation hépatique, Rennes, France
| | | | - Audrey Coilly
- AP-HP, Hôpital Paul Brousse, Centre Hépato-Biliaire, INSERM, Unité 1193, Université Paris-Saclay, Villejuif, France
| | - Jérôme Dumortier
- Hospices civils de Lyon, Hôpital Edouard Herriot, Unité de transplantation hépatique, et Université Claude Bernard Lyon 1, Lyon, France
| | - Mario Altieri
- Normandie Univ, UNICAEN, CHU de Caen Normandie, Research and Innovation Department and Methodology Platform, Biostatistics and Clinical Research Units, Caen, France
- UFR Santé Caen France: U1086 INSERM- "ANTICIPE", Caen, France
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Erard D, Steiner A, Boillot O, Thimonier E, Vallin M, Veyre F, Guillaud O, Radenne S, Dumortier J. Calcineurin-Inhibitor Discontinuation Could Reduce the Risk of De Novo Malignancies After Liver Transplantation for Alcohol-Related Liver Disease. Clin Transplant 2024; 38:e70014. [PMID: 39552184 DOI: 10.1111/ctr.70014] [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: 01/05/2024] [Revised: 05/29/2024] [Accepted: 10/14/2024] [Indexed: 11/19/2024]
Abstract
BACKGROUND De novo malignancies are one of the leading causes of death after liver transplantation (LT), particularly in patients transplanted for alcohol-related liver disease (ALD). This retrospective study aimed to assess risk factors for malignancies and to evaluate the impact of calcineurin inhibitor (CNI) discontinuation. METHODS From 1990 to 2015, all patients transplanted for ALD were included. RESULTS A total of 493 patients were included, 77.9% were male and the median age at LT was 54 years. After LT, 278 de novo malignancies were diagnosed in 214 patients (43.4%). The cumulative incidence of de novo malignancies was 16.3% at 5 years, 34.4% at 10 years, and 49.8% at 15 years. In multivariate analysis, the independent risk factors were male gender (HR = 1.6), and active or weaned smoking (HR = 2.0). Discontinuation of CNI was a protective factor (HR = 0.6). Survival after diagnosis of de novo malignancy was 42.7% at 5 years and 27.5% at 10 years. CONCLUSION Our results confirm the major incidence of de novo malignancies after LT for ALD, as well as the important role of non-modifiable risk factors such as smoking and gender. CNI discontinuation is a protective factor, and the only adaptable, and could be proposed in smoker male patients transplanted for ALD.
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Affiliation(s)
- Domitille Erard
- Service d'hépatologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
| | - Anouk Steiner
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Olivier Boillot
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
- Université Claude Bernard Lyon 1, Lyon, France
| | - Elsa Thimonier
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Mélanie Vallin
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Florian Veyre
- Service d'hépatologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
| | - Olivier Guillaud
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Sylvie Radenne
- Service d'hépatologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
| | - Jérôme Dumortier
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
- Université Claude Bernard Lyon 1, Lyon, France
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Anilir E. Longitudinal analysis of social and community factors effective in increasing the number of liver donors in the United States. Medicine (Baltimore) 2024; 103:e39694. [PMID: 39312310 PMCID: PMC11419490 DOI: 10.1097/md.0000000000039694] [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: 12/15/2023] [Accepted: 08/23/2024] [Indexed: 09/25/2024] Open
Abstract
In this research, it was aimed to evaluate of social and community factors effective in increasing the number of liver donors. Descriptive and relational scanning models were used to conduct the research. Data on liver donors was gathered from the USA Health Resources & Services Administration's Organ Procurement and Transplantation Network between 1988 and 2023. The United States (USA) World Bank Country Reports provided the mortality rates. The data was analyzed using Spearman rho correlation, year-controlled partial correlation, and Generalized Linear Model-Logit analysis. Deceased donor numbers were significantly and negatively correlated with government health expenditure (r = -0.816; P < .01), current health expenditure (r = -0.768; P < .01), female education attainment (r = -0.804; P < .01) and Gini index (r = 0.434; P < .05). Living donor numbers were significantly and negatively correlated with government health expenditure (r = -0.731; P < .01), current health expenditure (r = -0.781; P < .01), male percentage (r = -0.786; P < .01), female education attainment (r = -0.640; P < .05), employment (r = 0.751; P < .01), GDP (r = -0.792; P < .01) and Gini index (r = -0.486; P < .01). Living donor numbers were significantly and positively correlated with age dependency (r = 0.815; P < .01). Generalized Linear Model-Logit (GLM-L) results showed that effect of female education attainment had significant contribution on deceased liver donor (B = -3290.605; P < .01). Effects of significantly correlated community factors on living liver donor numbers were found to be statistically insignificant (P > .05). Research findings reveal that among community factors, especially women's participation in education has a statistically significant effect on liver donors. These results show that the health expenditures made over the years do not provide any added value for liver donors, and role of women on liver donor is significantly dominant.
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Affiliation(s)
- Ender Anilir
- Biruni University Hospital Organ Transplantation and Hepatobiliary Surgery Center, İstanbul, Turkey
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Waldron O, Kim A, Daoud D, Zhu J, Patel J, Butler T, Zhou S, Jain A. A Comparative Review of Standardized Incidence Ratios of De Novo Malignancies Post Liver Transplantation in Males Versus Females. Transplant Proc 2024; 56:1365-1373. [PMID: 39003208 DOI: 10.1016/j.transproceed.2024.01.065] [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: 09/18/2023] [Revised: 12/05/2023] [Accepted: 01/24/2024] [Indexed: 07/15/2024]
Abstract
After liver transplantation (LTx), the most common cause of death in the long-term is de-novo malignancy (DNM). The aim is to review the gender differences in the standardized incidence ratio (SIR) of DNM within the same geographical locations. METHODS Four studies were identified comparing post-LTx SIR between males and females. RESULTS From 6663 males and 2780 females LTx recipients, the mean SIR from each of the four studies for males is 2.8, 2.0, 1.94, and 3.4, and 3.5, 1.3, 1.95, and 2.3 for females. On meta-analysis using a random effect model for each gender group. No significant difference was revealed after logarithmic transformation and subgroup meta-analysis. Overall mean SIR with 95% Confidence Interval (CI) for males is 2.53 (95% CI 1.65-3.88) and 2.3 (1.25-4.24) for females. lung malignancy, 1.97 (1.14-3.41) for males and 2.65 (0.67-10.47) for females. For colorectal malignancy, the combined SIR for males is 1.98 (0.58-6.78) and 1.85 (1.02-3.37) for females. The SIR for female gender-specific malignancies; SIR for breast is 1.1 ± 4.4, cervix 2.9 ± 1.9, uterus 2.8, and ovarian 0.7, and for males, testis 1.6 ± 1.3, prostate 1.2 ± 0.4. However, rare malignancies, male breast cancers (n = 1, SIR, 22.6), and Kaposi's sarcoma, in males (n = 6) and in females (n = 1), had SIR 120. and 212.7, respectively. CONCLUSION Overall, there are no statistical differences between male and female DNM. Female-specific cervix, uterus, ovarian, and male-specific testis and prostate have similar SIR. Rare malignancies have very high SIR.
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Affiliation(s)
| | - Andrew Kim
- Penn State College of Medicine, Hershey, PA
| | - Deborah Daoud
- Department of General Surgery, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ
| | - Junjia Zhu
- Department of Public Health Sciences, The Pennsylvania State University College of Medicine, Hershey, PA
| | - Jay Patel
- Department of General Surgery, VCU Medical Center, Richmond, VA
| | - Thomas Butler
- Department of General Surgery, Division of Transplant Surgery, The Pennsylvania State University College of Medicine, Hershey, PA
| | - Shouhao Zhou
- Department of Public Health Sciences, The Pennsylvania State University College of Medicine, Hershey, PA
| | - Ashokkumar Jain
- Department of General Surgery, Division of Transplant Surgery, The Pennsylvania State University College of Medicine, Hershey, PA.
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9
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Mohan R, Rice J. A practical approach to extrahepatic cancer screening before and after liver transplant. Clin Liver Dis (Hoboken) 2023; 21:169-172. [PMID: 37361253 PMCID: PMC10287123 DOI: 10.1097/cld.0000000000000060] [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: 12/01/2022] [Accepted: 03/25/2023] [Indexed: 06/28/2023] Open
Affiliation(s)
- Rahul Mohan
- Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Jonathan Rice
- Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA
- Colorado Center for Transplantation Care, Research, and Education (CCTCARE), University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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10
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Fuochi E, Anastasio L, Lynch EN, Campani C, Dragoni G, Milani S, Galli A, Innocenti T. Main factors influencing long-term outcomes of liver transplantation in 2022. World J Hepatol 2023; 15:321-352. [PMID: 37034235 PMCID: PMC10075010 DOI: 10.4254/wjh.v15.i3.321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/24/2022] [Accepted: 02/22/2023] [Indexed: 04/11/2023] Open
Abstract
Liver transplant (LT) outcomes have markedly improved in the recent decades, even if long-term morbidity and mortality are still considerable. Most of late deaths are independent from graft function and different comorbidities, including complications of metabolic syndrome and de novo neoplasms, seem to play a key role in determining long-term outcomes in LT recipients. This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term management and follow-up after liver transplantation. In particular, the reduction of drug toxicity, the use of tools to identify high-risk patients, and setting up a multidisciplinary team also for long-term management of LT recipients may further improve survival after liver transplantation.
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Affiliation(s)
- Elisa Fuochi
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Lorenzo Anastasio
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Erica Nicola Lynch
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
- Department of Medical Biotechnologies, University of Siena, Siena 53100, Italy
| | - Stefano Milani
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Andrea Galli
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Tommaso Innocenti
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
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11
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Ji L, Xu D, Zhu C, Xu J, Cao H, Zhao G. Successful pancreatoduodenectomy of de novo duodenal malignancy after orthotopic liver transplantation: A case report. Front Surg 2023; 9:1068215. [PMID: 36684304 PMCID: PMC9852733 DOI: 10.3389/fsurg.2022.1068215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 11/30/2022] [Indexed: 01/09/2023] Open
Abstract
Introduction Liver transplantation is a risk factor for premalignant and malignant changes of the duodenum. De novo duodenal malignancy is seldom reported after liver transplantation. Case Report The present study reports a case of an asymptomatic 67-year-old male patient who underwent liver transplantation more than 10 years ago and subsequently developed duodenal malignancy. Endoscopic biopsy of the de novo duodenal malignancy indicated duodenal carcinoma and pancreatoduodenectomy (PD) was performed. The patient was successfully discharged 12 days after the surgery. A metastatic lesion occurred at the right seventh rib 14 months after the pancreatoduodenectomy. Postoperative pathological examination indicated hepatocellular carcinoma metastasis. Conclusions To the best of our knowledge, this case type has not been previously reported. The present study sheds light on the development, the treatment, the prognosis, and the management of a new type of de novo duodenal malignancy.
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Affiliation(s)
| | | | | | | | - Hui Cao
- Correspondence: Gang Zhao Hui Cao
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12
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A Reduction of Calcineurin Inhibitors May Improve Survival in Patients with De Novo Colorectal Cancer after Liver Transplantation. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58121755. [PMID: 36556957 PMCID: PMC9785597 DOI: 10.3390/medicina58121755] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 11/25/2022] [Accepted: 11/28/2022] [Indexed: 12/04/2022]
Abstract
Background and Objectives: After liver transplantation (LT), long-term immunosuppression (IS) is essential. IS is associated with de novo malignancies, and the incidence of colorectal cancer (CRC) is increased in LT patients. We assessed course of disease in patients with de novo CRC after LT with focus of IS and impact on survival in a retrospective, single-center study. Materials and Methods: All patients diagnosed with CRC after LT between 1988 and 2019 were included. The management of IS regimen following diagnosis and the oncological treatment approach were analyzed: Kaplan−Meier analysis as well as univariate and multivariate analysis were performed. Results: A total of 33 out of 2744 patients were diagnosed with CRC after LT. Two groups were identified: patients with restrictive IS management undergoing dose reduction (RIM group, n = 20) and those with unaltered regimen (maintenance group, n = 13). The groups did not differ in clinical and oncological characteristics. Statistically significant improved survival was found in Kaplan−Meier analysis for patients in the RIM group with 83.46 (8.4−193.1) months in RIM and 24.8 (0.5−298.9) months in the maintenance group (log rank = 0.02) and showed a trend in multivariate cox regression (p = 0.054, HR = 14.3, CI = 0.96−213.67). Conclusions: Immunosuppressive therapy should be reduced further in patients suffering from CRC after LT in an individualized manner to enable optimal oncological therapy and enable improved survival.
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13
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La Padula S, Pensato R, Pizza C, Coiante E, Roccaro G, Longo B, D’Andrea F, Wirz FS, Hersant B, Meningaud JP. Face Transplant: Indications, Outcomes, and Ethical Issues-Where Do We Stand? J Clin Med 2022; 11:jcm11195750. [PMID: 36233619 PMCID: PMC9571096 DOI: 10.3390/jcm11195750] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 09/13/2022] [Accepted: 09/26/2022] [Indexed: 11/21/2022] Open
Abstract
Background: The addition of face allotransplantation (FT) to the head and neck reconstructive surgery arsenal has started a true revolution. This study is aimed at providing an extensive analysis of the current practice of composite tissue allotransplantation. Moreover, a thorough description of pre-procedural, intra-operative, and post-procedural settings, indications, contraindications, outcomes, ethical considerations, and future perspectives is provided. Methods: The authors’ experience was supplemented with a literature review performed by using the PubMed, MEDLINE, and Embase databases on 21 February 2022. The search terms used were “face transplantation indications”, “face transplantation complications”, and “face transplantation ethical issues”. Results: The most recent achievements and long-term clinical sequelae of FT are classified and summarized. A large number of records (4435) were identified. Seventy-five articles were assessed for eligibility. Publications without new data and reports with a patient follow-up < 5 years were excluded. Nineteen articles met the criteria for inclusion. Conclusions: The most recent achievements in the field of FT may be combined with cutting-edge regenerative medicine procedures and innovative immunological processing. It is paramount to build strong international networks between the world FT experts in order to achieve higher-level outcomes and reduce the complication rate. Nevertheless, the utmost caution is required in patient selection, clinical assessment, strict follow-up, and rejection management.
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Affiliation(s)
- Simone La Padula
- Department of Plastic and Reconstructive Surgery, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131 Napoli, Italy
- Department of Plastic, Reconstructive and Maxillo Facial Surgery, Henri Mondor Hospital, University Paris XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
- Correspondence:
| | - Rosita Pensato
- Department of Plastic and Reconstructive Surgery, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131 Napoli, Italy
| | - Chiara Pizza
- Department of Plastic, Reconstructive and Maxillo Facial Surgery, Henri Mondor Hospital, University Paris XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
| | - Edoardo Coiante
- Department of Plastic, Reconstructive and Maxillo Facial Surgery, Henri Mondor Hospital, University Paris XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
| | - Giovanni Roccaro
- Department of Plastic, Reconstructive and Maxillo Facial Surgery, Henri Mondor Hospital, University Paris XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
| | - Benedetto Longo
- Department of Plastic and Reconstructive Surgery, Università di Roma Tor Vergata, Viale Oxford 81, 00133 Roma, Italy
| | - Francesco D’Andrea
- Department of Plastic and Reconstructive Surgery, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131 Napoli, Italy
| | | | - Barbara Hersant
- Department of Plastic, Reconstructive and Maxillo Facial Surgery, Henri Mondor Hospital, University Paris XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
| | - Jean Paul Meningaud
- Department of Plastic, Reconstructive and Maxillo Facial Surgery, Henri Mondor Hospital, University Paris XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
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14
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Fodor M, Zoller H, Oberhuber R, Sucher R, Seehofer D, Cillo U, Line PD, Tilg H, Schneeberger S. The Need to Update Endpoints and Outcome Analysis in the Rapidly Changing Field of Liver Transplantation. Transplantation 2022; 106:938-949. [PMID: 34753893 DOI: 10.1097/tp.0000000000003973] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Liver transplantation (LT) survival rates have continued to improve over the last decades, mostly due to the reduction of mortality early after transplantation. The advancement is facilitating a liberalization of access to LT, with more patients with higher risk profiles being added to the waiting list. At the same time, the persisting organ shortage fosters strategies to rescue organs of high-risk donors. This is facilitated by novel technologies such as machine perfusion. Owing to these developments, reconsideration of the current and emerging endpoints for the assessment of the efficacy of existing and new therapies is warranted. While conventional early endpoints in LT have focused on the damage induced to the parenchyma, the fate of the bile duct and the recurrence of the underlying disease have a stronger impact on the long-term outcome. In light of this evolving landscape, we here attempt to reflect on the appropriateness of the currently used endpoints in the field of LT trials.
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Affiliation(s)
- Margot Fodor
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Heinz Zoller
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Rupert Oberhuber
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Robert Sucher
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Clinic, Leipzig, Germany
| | - Daniel Seehofer
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Clinic, Leipzig, Germany
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplant Unit, Padua University Hospital, Padua, Italy
| | - Pal Dag Line
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
- Institute for Clinical Medicine, University of Oslo, Oslo, Norway
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Stefan Schneeberger
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
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15
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Gitto S, Magistri P, Marzi L, Mannelli N, De Maria N, Mega A, Vitale G, Valente G, Vizzutti F, Villa E, Marra F, Andreone P, Falcini M, Catellani B, Guerrini GP, Serra V, Di Sandro S, Ballarin R, Piai G, Schepis F, Margotti M, Cursaro C, De Simone P, Petruccelli S, Carrai P, Forte P, Campani C, Zoller H, Di Benedetto F. Predictors of solid extra-hepatic non-skin cancer in liver transplant recipients and analysis of survival: A long-term follow-up study. Ann Hepatol 2022; 27:100683. [PMID: 35151902 DOI: 10.1016/j.aohep.2022.100683] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 02/02/2022] [Accepted: 02/02/2022] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES De novo malignancies represent an important cause of death for liver transplant recipients. Our aim was to analyze predictors of extra-hepatic non-skin cancer (ESNSC) and the impact of ESNSC on the long-term outcome. PATIENTS We examined data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics with a retrospective observational cohort study. Cox Regression was performed to identify predictors of ESNSC. A 1:2 cohort sub-study was developed to analyze the impact of ESNSC on 10-year survival. RESULTS We analyzed data from 367 subjects (median follow-up: 15 years). Patients with ESNSC (n = 47) more often developed post-LT diabetes mellitus (DM) (57.4% versus 35,9%, p = 0.004). At multivariate analysis, post-LT DM independently predicted ESNSC (HR 1.929, CI 1.029-3.616, p = 0.040). Recipients with ESNSC showed a lower 10-year survival than matched controls (46,8% versus 68,1%, p = 0.023). CONCLUSIONS Post-LT DM seems to be a relevant risk factor for post-LT ESNSC. ESNSC could have a noteworthy impact on the long-term survival of LT recipients.
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Affiliation(s)
- Stefano Gitto
- Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, University Hospital Careggi, University of Florence, Largo Brambilla 3, Florence 50134, Italy.
| | - Paolo Magistri
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Luca Marzi
- Division of Gastroenterology, Bolzano Regional Hospital, Bolzano, Italy
| | - Nicolò Mannelli
- Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, University Hospital Careggi, University of Florence, Largo Brambilla 3, Florence 50134, Italy
| | - Nicola De Maria
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Andrea Mega
- Division of Gastroenterology, Bolzano Regional Hospital, Bolzano, Italy
| | | | - Giovanna Valente
- Liver Unit for Transplant Management - SATTE, Department of Medical Sciences, AORN Sant'Anna e San Sebastiano, Caserta, Italy
| | - Francesco Vizzutti
- Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, University Hospital Careggi, University of Florence, Largo Brambilla 3, Florence 50134, Italy
| | - Erica Villa
- Department of Gastroenterology, Azienda Ospedaliero-Universitaria di Modena and University of Modena and Reggio Emilia, Modena, Italy
| | - Fabio Marra
- Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, University Hospital Careggi, University of Florence, Largo Brambilla 3, Florence 50134, Italy
| | - Pietro Andreone
- Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, University of Bologna, Italy; Internal and Metabolic Medicine, AOU di Modena and University of Modena and Reggio Emilia, Italy
| | - Margherita Falcini
- Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, University Hospital Careggi, University of Florence, Largo Brambilla 3, Florence 50134, Italy
| | - Barbara Catellani
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Gian Piero Guerrini
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Valentina Serra
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Stefano Di Sandro
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Roberto Ballarin
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Guido Piai
- Liver Unit for Transplant Management - SATTE, Department of Medical Sciences, AORN Sant'Anna e San Sebastiano, Caserta, Italy
| | - Filippo Schepis
- Department of Gastroenterology, Azienda Ospedaliero-Universitaria di Modena and University of Modena and Reggio Emilia, Modena, Italy
| | - Marzia Margotti
- Internal and Metabolic Medicine, AOU di Modena and University of Modena and Reggio Emilia, Italy
| | - Carmela Cursaro
- Internal and Metabolic Medicine, AOU di Modena and University of Modena and Reggio Emilia, Italy
| | - Paolo De Simone
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Stefania Petruccelli
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Paola Carrai
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Paolo Forte
- Gastroenterology Unit, University Hospital Careggi, Florence, Italy
| | - Claudia Campani
- Gastroenterology Unit, University Hospital Careggi, Florence, Italy
| | - Heinz Zoller
- Department of Medicine I, Medical University of Innsbruck, Austria
| | - Fabrizio Di Benedetto
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
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16
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Hai Nam N, Taura K, Koyama Y, Nishio T, Yamamoto G, Uemoto Y, Kimura Y, Xuefeng L, Nakamura D, Yoshino K, Ogawa E, Okamoto T, Yoshizawa A, Seo S, Iwaisako K, Yoh T, Hata K, Masui T, Okajima H, Haga H, Uemoto S, Hatano E. Increased Expressions of Programmed Death Ligand 1 and Galectin 9 in Transplant Recipients Who Achieved Tolerance After Immunosuppression Withdrawal. Liver Transpl 2022; 28:647-658. [PMID: 34655506 DOI: 10.1002/lt.26336] [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: 08/21/2021] [Revised: 09/27/2021] [Accepted: 10/06/2021] [Indexed: 01/13/2023]
Abstract
Programmed death 1 (PD1)/its ligand PD-L1 concomitant with T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3)/its ligand galectin 9 (Gal-9) and the forkhead box P3 (FOXP3) might be involved in tolerance after liver transplantation (LT). Liver biopsies from 38 tolerant, 19 nontolerant (including 16 samples that triggered reintroduction of immunosuppression [IS] and 19 samples after IS reintroduction), and 38 control LT patients were studied. The expressions of PD1, PD-L1, Gal-9, and FOXP3 were determined by immunohistochemical and immunofluorescence (IF) staining. The success period of IS withdrawal was calculated using Kaplan-Meier curve analysis. Tolerant and control patients exhibited higher PD-L1, Gal-9, and FOXP3 levels than nontolerant patients at the moment of triggering IS reintroduction. High expressions of PD-L1 and Gal-9 were associated with prolonged success of tolerance (83.3% versus 36.7% [P < 0.01] and 73.1% versus 42.9% [P = 0.03]). A strong correlation between PD-L1 and Gal-9 expression levels was detected (Spearman r = 0.73; P ≤ 0.001), and IF demonstrated colocalization of PD-L1 and Gal-9 in the cytoplasm of hepatocytes. In conclusion, the present study demonstrated that increased expressions of PD-L1 and Gal-9 were associated with sustained tolerance after IS withdrawal in pediatric liver transplantation.
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Affiliation(s)
- Nguyen Hai Nam
- Division of Hepato Biliary Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kojiro Taura
- Division of Hepato Biliary Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yukinori Koyama
- Division of Hepato Biliary Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takahiro Nishio
- Division of Hepato Biliary Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Gen Yamamoto
- Division of Hepato Biliary Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yusuke Uemoto
- Division of Hepato Biliary Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yusuke Kimura
- Division of Hepato Biliary Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Li Xuefeng
- Division of Hepato Biliary Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Daichi Nakamura
- Division of Hepato Biliary Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kenji Yoshino
- Department of Surgery, Nagahama City Hospital, Nagahama, Japan
| | - Eri Ogawa
- Department of Pediatric Surgery, Kyoto University Hospital, Kyoto, Japan
| | - Tatsuya Okamoto
- Department of Pediatric Surgery, Kyoto University Hospital, Kyoto, Japan
| | | | - Satoru Seo
- Division of Hepato Biliary Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Keiko Iwaisako
- Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan
| | - Tomoaki Yoh
- Division of Hepato Biliary Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Koichiro Hata
- Division of Hepato Biliary Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Toshihiko Masui
- Division of Hepato Biliary Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hideaki Okajima
- Department of Pediatric Surgery, Kanazawa Medical University, Ishikawa, Japan
| | - Hironori Haga
- Department of Diagnostic Pathology, Kyoto University, 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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17
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Wells MW, Rampazzo A, Papay F, Gharb BB. Two Decades of Hand Transplantation: A Systematic Review of Outcomes. Ann Plast Surg 2022; 88:335-344. [PMID: 35113506 DOI: 10.1097/sap.0000000000003056] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
ABSTRACT Hand transplantation for upper extremity amputation provides a unique treatment that restores form and function, which may not be achieved by traditional reconstruction and prosthetics. However, despite enhancing quality of life, hand transplantation remains controversial, because of immunological complications, transplant rejection, and medication effects. This systematic literature review sought to collect information on current experiences and outcomes of hand transplants to determine the efficacy and utility of hand transplants. The databases PubMed, Scopus, and Embase were analyzed with combinations of "hand" or "upper extremity" or "arm" and "transplant" or "allograft," with information collected on recipient characteristics, details of transplant, immunological outcomes, functional outcomes, and complications. Functional outcomes, as measured by Disabilities of Arm, Shoulder and Hand score, were compared between patient groups using Wilcoxon signed-rank test or 1-way analysis of variance test and post hoc Tukey test. Within the 108 articles that fulfilled inclusion and exclusion criteria, there were 96 patients with 148 hand transplants. There were 57 patients who experienced acute rejection and 5 patients with chronic rejection. Disabilities of the Arm, Shoulder and Hand scores significantly decreased after hand transplantation and were significantly lower for distal transplants compared with proximal transplants. There were 3 patients with concurrent face transplantation and 2 patients with simultaneous leg transplants. Sixteen patients experienced amputation of the hand transplant, and there were 5 deaths. This study found that hand transplantation provides significant restoration of function and form, especially for proximal transplants. Reduction in complications, such as rejection and amputation, can be achieved by decreasing medication cost and patient education.
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Affiliation(s)
- Michael W Wells
- From the Case Western Reserve University, School of Medicine
| | | | - Francis Papay
- Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH
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18
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Toniutto P, Germani G, Ferrarese A, Bitetto D, Zanetto A, Fornasiere E, Fumolo E, Shalaby S, Burra P. An Essential Guide for Managing Post-Liver Transplant Patients: What Primary Care Physicians Should Know. Am J Med 2022; 135:157-166. [PMID: 34508700 DOI: 10.1016/j.amjmed.2021.08.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 08/11/2021] [Accepted: 08/11/2021] [Indexed: 12/16/2022]
Abstract
With long-term survival after liver transplantation becoming the rule, care for medical problems arising over time in liver-transplanted patients gained increasing importance. The most common causes of death occurring more than 1 year after liver transplantation are unrelated to liver diseases and facilitated by immunosuppressive treatments; examples are malignancies, renal failure, and cardiovascular, metabolic, and infectious diseases. Recipients receive life-long follow-up care at transplant centers, however, the increasing number of liver-transplanted patients is saturating the health care supply that transplant centers have to offer. Primary care physicians are increasingly exposed to liver-transplanted patients, even in the early periods after transplant, and an understanding of the most common risks and complications faced by these patients would enhance their care. This article reviews the long-term care of liver transplant recipients, emphasizing the key internal medicine-related issues that should be known by primary care physicians. A specific section is devoted to implementing strategies to involve these physicians in the long-term follow-up of liver-transplanted patients in close collaboration with transplant hepatologists.
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Affiliation(s)
- Pierluigi Toniutto
- Hepatology and Liver Transplantation Unit, Department of Specialized Medicine, Udine University Hospital, Udine, Italy;.
| | - Giacomo Germani
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Alberto Ferrarese
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Davide Bitetto
- Hepatology and Liver Transplantation Unit, Department of Specialized Medicine, Udine University Hospital, Udine, Italy
| | - Alberto Zanetto
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Ezio Fornasiere
- Hepatology and Liver Transplantation Unit, Department of Specialized Medicine, Udine University Hospital, Udine, Italy
| | - Elisa Fumolo
- Hepatology and Liver Transplantation Unit, Department of Specialized Medicine, Udine University Hospital, Udine, Italy
| | - Sarah Shalaby
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
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19
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Herreras López J, Puchades L, Di Maira T, Cañada AJ, Maupoey J, López-Andújar R, Prieto Castillo M, Berenguer Haym M, Aguilera V. Metabolic syndrome before liver transplantation: does it have an impact on post liver transplantation outcomes? REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2022; 114:586-591. [PMID: 35045717 DOI: 10.17235/reed.2022.8384/2021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
INTRODUCTION Metabolic syndrome (MS) and cardiovascular risk factors are commonin liver transplant (LT) candidates and recipients. Cardiovascular events and de novo tumours are increasingly common causes of mortality in liver transplant recipients. The aim of this study is (i) to assess the prevalence of MS in LT recipients and its growth over the years and (ii) if the presence of MS pre-LT is associated with a higher risk of post-LT cardiovascular events (CVE), de novo tumours or early and late survival. PATIENTS AND METHODS Retrospective study that included LT recipients from January 2012 to December 2017. Baseline features (MS before LT and at 1year post-LT) and outcomes (CVE, de novo tumours and survival) were recorded. RESULTS 483 recipients were included, MS was present pre-LT in 20% with an increasing prevalence over time, from16% in 2012 to 34% in 2017 (p=0.025). One-year post-LT, an additional 12% had developed de novo MS .At a median of 56-months follow-up, 13% developed a CVE and 9% a de novo tumour. One and 5-yr survival rates were91% and 83 % in those with pre-LT MS and 93% and 85 % in those without (p=0.94).The presence of MS before LT was independently associated with a higher risk of post-LT CVE (HR: 2.66 IC (95%): 1.6-4.4 p< 0.001), but not with de novo tumors (p=0.94) nor early and late survival (p=0.58 and p=0.87). CONCLUSION Pre-LT MS is increasing among LT candidates and is associated with a higher risk of post-LT morbidity CVE yet without affecting mortality.
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Affiliation(s)
| | - Lorena Puchades
- Medicina Digestiva, Hospital Universitari i Politècnic La Fe
| | | | | | - Javier Maupoey
- Hepatología de Medicina Digestiva, Hospital Politècnic i Universitari La Fe
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20
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Salcedo M, Vinaixa C, Javle M, Trapero-Marugán M, Bustamante J, Line PD. Evaluation and Management of Liver Transplant Candidates With Prior Nonhepatic Cancer: Guidelines From the ILTS/SETH Consensus Conference. Transplantation 2022; 106:e3-e11. [PMID: 34905758 DOI: 10.1097/tp.0000000000003997] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Liver transplant in patients with prior nonhepatic cancer is a matter of concern, needing further research, development, and consensus guidelines. This International Liver Transplantation Society/Sociedad Española De Trasplante Hepático consensus conference document focuses on the role of liver transplantation in patients with a prior history of nonhepatic cancer. This document addresses (1) the evaluation of transplant candidates with prior cancers based on the assessment of prognosis, the natural history of individual cancers, and the emerging role for circulating DNA and minimal residual disease in these patients; (2) the impact of prior treatments, including immunotherapy for prior malignancies; and (3) the surveillance of posttransplant cancer recurrence. The consensus statement is based on previously published guidelines, as well as a review of the current, relevant, published literature.
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Affiliation(s)
- Magdalena Salcedo
- Hepatology and Liver Transplantation Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Carmen Vinaixa
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Department of Hepatology and Liver Transplantation, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - Milind Javle
- GI Oncology Unit, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - María Trapero-Marugán
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Liver Unit, Hospital Universitario Puerta de Hierro Majadahonda, Instituto de Investigación Puerta de Hierro Segovia Arana IDIPHISA, Madrid, Spain
| | - Javier Bustamante
- Liver Transplant and Hepatology Unit, Cruces University Hospital, Baracaldo, Vizcaya, Spain
| | - Pål-Dag Line
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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21
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Kim M, Kim CW, Hwang S, Kim YH, Lee JL, Yoon YS, Park IJ, Lim SB, Yu CS, Kim JC, Han DJ, Lee SG. Characteristics and Prognosis of Colorectal Cancer after Liver or Kidney Transplantation. World J Surg 2021; 45:3206-3213. [PMID: 34235562 DOI: 10.1007/s00268-021-06219-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/31/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND The purpose of this study was to evaluate the characteristics and prognosis of de novo CRC patients who underwent liver or kidney transplantation. METHODS We retrospectively reviewed the medical records of 66 de novo CRC patients selected from 8,734 liver transplant (LT) or kidney transplant (KT) recipients. We analyzed characteristics and survival outcomes of de novo CRC patients and sporadic CRC patients who underwent radical surgery with stage I-III in Asan Medical Center between 2005 and 2016. Survival outcomes were analyzed via the 1:4 matching method. RESULTS The standard incidence ratio (SIR) of de novo CRC in KT recipients is 1.67 in men and 2.54 in women. That in LT recipients is 3.10 in men and 2.25 in women. Compared with sporadic CRC patients, de novo CRC patients had more colon cancer than rectal cancer (p=0.041). In 9 patients (13.6%), CRC was diagnosed within one year after transplantation, 21 patients (31.8%) were diagnosed between 1-5 years, and the remaining 36 patients (54.6%) were diagnosed thereafter. There were no significant differences in recurrence-free survival and overall survival between the two groups (p=0.211 and p=0.324, respectively). CONCLUSIONS The risk of developing de novo CRC in transplant recipients was higher than in the general population. The survival outcome of de novo CRC was no different compared with the sporadic CRC. Therefore, regular surveillance is essential for timely diagnosis and treatment for transplantation patients. A large prospective study for an intense CRC surveillance program in transplantation patients is needed.
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Affiliation(s)
- Minsung Kim
- Department of Colon & Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Chan Wook Kim
- Department of Colon & Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.
| | - Shin Hwang
- Department of Hepatobiliary & Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Young Hoon Kim
- Department of Kidney and Pancreas Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Jong Lyul Lee
- Department of Colon & Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Yong Sik Yoon
- Department of Colon & Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - In Ja Park
- Department of Colon & Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Seok-Byung Lim
- Department of Colon & Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Chang Sik Yu
- Department of Colon & Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Jin Cheon Kim
- Department of Colon & Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Duck Jong Han
- Department of Kidney and Pancreas Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Sung-Gyu Lee
- Department of Hepatobiliary & Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
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22
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Lucidi C, Biolato M, Lai Q, Lattanzi B, Lenci I, Milana M, Lionetti R, Liguori A, Angelico M, Tisone G, Avolio AW, Agnes S, Rossi M, Grieco A, Merli M. Cumulative incidence of solid and hematological De novo malignancy after liver transplantation in a multicentre cohort. Ann Hepatol 2021; 24:100309. [PMID: 33482364 DOI: 10.1016/j.aohep.2021.100309] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 12/16/2020] [Accepted: 12/16/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Recent innovations in the field of liver transplantation have led to a wealth of new treatment regimes, with potential impact on the onset of de novo malignancies (DNM). The aim of this multicenter cohort study was to provide contemporary figures for the cumulative incidences of solid and hematological DNM after liver transplantation. METHODS We designed a retrospective cohort study including patients undergoing LT between 2000 and 2015 in three Italian transplant centers. Cumulative incidence was calculated by Kaplan-Meyer analysis. RESULTS The study included 789 LT patients with a median follow-up of 81 months (IQR: 38-124). The cumulative incidence of non-cutaneous DNM was 6.2% at 5-years, 11.6% at 10-years and 16.3% at 15-years. Post-Transplant Lymphoproliferative Disorders (PTLD) were demonstrated to have a cumulative incidence of 1.0% at 5-years, 1.6% at 10-years and 2.2% at 15-years. Solid Organ Tumors (SOT) demonstrated higher cumulative incidences - 5.3% at 5-years, 10.3% at 10-years and 14.4% at 15-years. The most frequently observed classifications of SOT were lung (rate 1.0% at 5-years, 2.5% at 10-years) and head & neck tumors (rate 1.3% at 5-years, 1.9% at 10-years). CONCLUSIONS Lung tumors and head & neck tumors are the most frequently observed SOT after LT.
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Affiliation(s)
- Cristina Lucidi
- Gastroenterology, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Marco Biolato
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Catholic University of the Sacred Heart, Rome, Italy
| | - Quirino Lai
- Hepato-biliopancreatic and Liver Transplant Unit, Department of Surgery, Sapienza University of Rome, Rome, Italy
| | - Barbara Lattanzi
- Gastroenterology, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Ilaria Lenci
- Hepatology Unit, Department of Experimental Medicine and Surgery, Tor Vergata University Hospital, Rome, Italy
| | - Martina Milana
- Hepatology Unit, Department of Experimental Medicine and Surgery, Tor Vergata University Hospital, Rome, Italy
| | - Raffaella Lionetti
- Infectious and Liver Diseases, Lazzaro Spallanzani National Infectious Disease Institute, Rome, Italy
| | | | - Mario Angelico
- Hepatology Unit, Department of Experimental Medicine and Surgery, Tor Vergata University Hospital, Rome, Italy
| | - Giuseppe Tisone
- Surgery Unit, Department of Experimental Medicine and Surgery, Tor Vergata University Hospital, Rome, Italy
| | - Alfonso Wolfango Avolio
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Catholic University of the Sacred Heart, Rome, Italy
| | - Salvatore Agnes
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Catholic University of the Sacred Heart, Rome, Italy
| | - Massimo Rossi
- Hepato-biliopancreatic and Liver Transplant Unit, Department of Surgery, Sapienza University of Rome, Rome, Italy
| | - Antonio Grieco
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Catholic University of the Sacred Heart, Rome, Italy
| | - Manuela Merli
- Gastroenterology, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
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23
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Altieri M, Sérée O, Lobbedez T, Segol P, Abergel A, Blaizot X, Boillot O, Boudjema K, Coilly A, Conti F, Chazouillères O, Debette-Gratien M, Dharancy S, Durand F, Duvoux C, Francoz C, Gugenheim J, Hardwigsen J, Houssel-Debry P, Kamar N, Latournerie M, Lebray P, Leroy V, Neau-Cransac M, Pageaux GP, Radenne S, Salamé E, Saliba F, Samuel D, Vanlemmens C, Besch C, Launoy G, Dumortier J. Risk factors of de novo malignancies after liver transplantation: a French national study on 11004 adult patients. Clin Res Hepatol Gastroenterol 2021; 45:101514. [PMID: 33714907 DOI: 10.1016/j.clinre.2020.07.019] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 07/13/2020] [Accepted: 07/13/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND After liver transplantation (LT),de novo malignancies are one of the leading causes of late mortality. The aim of the present retrospective study was to identify the risk factors of de novo malignancies in a large cohort of LT recipients in France, using Fine and Gray competing risks regression analysis. METHODS The study population consisted in 11004 adults transplanted between 2000 and 2013, who had no history of pre-transplant malignancy, except primary liver tumor. A Cox model adapted to the identification of prognostic factors (competitive risks) was used. RESULTS From the entire cohort, one (or more)de novo malignancy was reported in 1480 L T recipients (13.45%). The probability to develop a de novo malignancy after LT was 2.07% at 1 year, 13.30% at 5 years, and 28.01% at 10 years. Of the known reported malignancies, the most common malignancies were hematological malignancy (22.36%), non-melanoma skin cancer (19.53%) and lung cancer (12.36%). According to Fine and Gray competing risks regression multivariate analysis, were significant risk factors for post-LT de novo malignancy: recipient age (Subdistribution Hazard Ratio (SHR) = 1.03 95%CI 1.03-1.04), male gender (SHR = 1.45 95%CI 1.27-1.67), non-living donor (SHR = 1.67 95%CI 1.14-2.38), a first LT (SHR = 1.35 95%CI 1.09-1.69) and the type of initial liver disease (alcohol-related liver disease (SHR = 1.63 95%CI 1.22-2.17), primary sclerosing cholangitis (SHR = 1.98 95%CI 1.34-2.91), and primary liver tumor (SHR = 1.88 95%CI 1.41-2.54)). Initial immunosuppressive regimen had no significant impact. CONCLUSION The present study confirms that LT recipient characteristics are associated with the risk ofde novo malignancy and this underlines the need for personalized screening in order to improve survival.
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Affiliation(s)
- Mario Altieri
- Hôpital Côte de Nacre, Service d'Hépato-Gastroentérologie, Nutrition et Oncologie Digestive, Caen, France; UFR Santé Caen France: U1086 INSERM- "ANTICIPE", Caen, France
| | - Olivier Sérée
- Réseau Régional de Cancérologie OncoBasseNormandie, Caen, France
| | - Thierry Lobbedez
- Hôpital Côte de Nacre, Néphrologie, CUMR CAEN CEDEX, France, Normandie Université, Unicaen UFR de Médecine, RDPLF, Caen, France
| | - Philippe Segol
- Hôpital Côte de Nacre, Service de chirurgie digestive et générale, Caen, France
| | - Armand Abergel
- CHU Estaing, Médecine Digestive, Institut Pascal., UMR 6602 UCA CNRS SIGMA, Clermont-Ferrand, France
| | - Xavier Blaizot
- Réseau Régional de Cancérologie OncoBasseNormandie, Caen, France
| | - Olivier Boillot
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Unité de Transplantation Hépatique, et Université Claude Bernard Lyon 1, France
| | - Karim Boudjema
- Hôpital Universitaire de Pontchaillou, Service d'Hépatologie et Transplantation Hépatique, Rennes, France
| | - Audrey Coilly
- AP-HP, Hôpital Paul Brousse, Centre Hépato-Biliaire, INSERM, Unité 1193, Villejuif, France
| | - Filomena Conti
- APHP - Hôpital de la Pitié Salpétrière, Service d'Hépatologie et Transplantation Hépatique, Paris, France
| | - Olivier Chazouillères
- AP-HP, Hôpital Saint-Antoine, Service d'Hépatologie, INSERM UMR S 938, CDR Saint-Antoine, Centre de Référence « Maladies inflammatoire des voies biliaires et hépatite auto-immune », Filière FILFOIE, Université Paris 6, UMR_S 938, CDR Saint-Antoine, Paris, France
| | - Maryline Debette-Gratien
- CHU Limoges, Service d'hépato-Gastroentérologie,, INSERM, U850, Université Limoges, Limoges, France
| | | | - François Durand
- APHP, Hôpital Beaujon, Service d'Hépatologie et Transplantation Hépatique - Université Paris Diderot - INSERM U1149, Clichy, France
| | | | - Claire Francoz
- APHP, Hôpital Beaujon, Service d'Hépatologie et Transplantation Hépatique - Université Paris Diderot - INSERM U1149, Clichy, France
| | - Jean Gugenheim
- Hôpital Universitaire de Nice, Service de Chirurgie Digestive et de Transplantation Hépatique - Université de Nice-Sophia-Antipolis, Nice, France
| | - Jean Hardwigsen
- APHM, Hôpital La Timone, Service Chirurgie Générale et Transplantation Hépatique Marseille, France
| | - Pauline Houssel-Debry
- Hôpital Universitaire de Pontchaillou, Service d'Hépatologie et Transplantation Hépatique, Rennes, France
| | - Nassim Kamar
- CHU Rangueil, Département de Néphrologie et Transplantation d'Organes, Toulouse, France
| | - Marianne Latournerie
- CHU Dijon, Service d'Hépato-gastroentérologie et Oncologie Digestive, Inserm EPICAD LNC-UMR1231, Université de Bourgogne-Franche Comté, Dijon, France
| | - Pascal Lebray
- CHU Dijon, Service d'Hépato-gastroentérologie et Oncologie Digestive, Inserm EPICAD LNC-UMR1231, Université de Bourgogne-Franche Comté, Dijon, France
| | - Vincent Leroy
- CHU Grenoble-Alpes, Service d'hépato-gastroentérologie, La Tronche, France
| | - Martine Neau-Cransac
- CHU de Bordeaux, Hôpital Haut Lévêque, Service de Chirurgie Hépatobiliaire et de Transplantation Hépatique, Bordeaux, France
| | | | - Sylvie Radenne
- Hospices civils de Lyon, Hôpital de la Croix-Rousse, Service d'Hépato-Gastroentérologie, Lyon, France
| | - Ephrem Salamé
- CHU Tours, Hôpital Trousseau Service de chirurgie digestive, oncologique et endocrinienne, Transplantation hépatique, Tours, France
| | - Faouzi Saliba
- AP-HP, Hôpital Paul Brousse, Centre Hépato-Biliaire, INSERM, Unité 1193, Villejuif, France
| | - Didier Samuel
- AP-HP, Hôpital Paul Brousse, Centre Hépato-Biliaire, INSERM, Unité 1193, Villejuif, France
| | - Claire Vanlemmens
- Hôpital Jean Minjoz, Service d'Hépatologie et Soins Intensifs Digestifs, Besançon, France
| | - Camille Besch
- CHRU Hautepierre, Service de chirurgie hépato-bilio-pancréatique et transplantation hépatique, Strasbourg, France
| | - Guy Launoy
- UFR Santé Caen France: U1086 INSERM- "ANTICIPE", Caen, France
| | - Jérôme Dumortier
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Unité de Transplantation Hépatique, et Université Claude Bernard Lyon 1, France.
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24
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Peruhova M, Peshevska-Sekulovska M, Panayotova G, Velikova T. Foremost Concepts in Mechanisms of De Novo Post-Liver Transplantation Malignancy. GASTROENTEROLOGY INSIGHTS 2021; 12:283-292. [DOI: 10.3390/gastroent12030025] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
In liver transplant patients, solid tumors and post-transplant lymphoproliferative disorders (PTLD) have emerged as significant long-term mortality causes. Additionally, it is assumed that de novo malignancy (DNM) after liver transplantation (LT) is the second-leading cause of death after cardiovascular complications. Well-established risk factors for PTLD and solid tumors are calcineurin inhibitors (CNIs), tacrolimus (TAC), and cyclosporine, the cornerstones of all immunosuppressive (IS) therapies used after LT. The loss of immunocompetence facilitated by the host immune system due to prolonged IS therapy leads to cancer development, including in LT patients. Hindering DNA repair mechanisms, promoting tumor cell invasiveness, and hampering apoptosis are critical events in tumorigenesis and tumor growth in LT patients resulting from IS administration. This paper aims to overview the refined mechanisms of IS-induced tumorigenesis after LT and the loss of immunocompetence facilitated by the host immune system due to prolonged IS therapy. In addition, we also discuss in detail the mechanisms of action in different types of IS regimen used after LT, and their putative effect on DNM.
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Affiliation(s)
- Milena Peruhova
- Department of Gastroenterology, University Hospital Lozenetz, 1 Kozyak str., 1407 Sofia, Bulgaria
| | | | - Gabriela Panayotova
- Department of Gastroenterology, University Hospital Lozenetz, 1 Kozyak str., 1407 Sofia, Bulgaria
| | - Tsvetelina Velikova
- Department of Clinical Immunology, Medical Faculty, University Hospital Lozenetz, Sofia University, St. Kliment Ohridski, 1407 Sofia, Bulgaria
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25
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Shalaby S, Taborelli M, Zanetto A, Ferrarese A, D'Arcangelo F, Gambato M, Senzolo M, Russo FP, Germani G, Boccagni P, Ettorre GM, Baccarani U, Lauro A, Galatioto L, Rendina M, Petrara R, De Rossi A, Nudo F, Toti L, Fantola G, Vennarecci G, Risaliti A, Pinna AD, Gruttadauria S, Di Leo A, Rossi M, Tisone G, Zamboni F, Cillo U, Piselli P, Serraino D, Burra P. Hepatocellular carcinoma and the risk of de novo malignancies after liver transplantation - a multicenter cohort study. Transpl Int 2021; 34:743-753. [PMID: 33492715 DOI: 10.1111/tri.13831] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 09/22/2020] [Accepted: 01/20/2021] [Indexed: 02/05/2023]
Abstract
Patients with hepatocellular carcinoma (HCC) are at high risk of second primary malignancies. As HCC has become the leading indication of liver transplant (LT), the aim of this study was to investigate whether the presence of HCC before LT could influence the onset of de novo malignancies (DNM). A cohort study was conducted on 2653 LT recipients. Hazard ratios (HR) of DNM development for patients transplanted for HCC (HCC patients) were compared with those of patients without any previous malignancy (non-HCC patients). All models were adjusted for sex, age, calendar year at transplant, and liver disease etiology. Throughout 17 903 person-years, 6.6% of HCC patients and 7.4% of non-HCC patients developed DNM (202 cases). The median time from LT to first DNM diagnosis was shorter for solid tumors in HCC patients (2.7 vs 4.5 years for HCC and non-HCC patients, respectively, P < 0.01). HCC patients were at a higher risk of bladder cancer and skin melanoma. There were no differences in cumulative DNM-specific mortality by HCC status. This study suggests that primary HCC could be a risk factor for DNM in LT recipients, allowing for risk stratification and screening individualization.
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Affiliation(s)
- Sarah Shalaby
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Martina Taborelli
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Alberto Zanetto
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Alberto Ferrarese
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Francesca D'Arcangelo
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Marco Senzolo
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Francesco Paolo Russo
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Giacomo Germani
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Patrizia Boccagni
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | | | | | - Augusto Lauro
- Liver and Multiorgan Transplant Unit, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Laura Galatioto
- Department of Gastroenterology and Hepatology, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), University of Pittsburgh Medical Center, Palermo, Italy
| | - Maria Rendina
- Department of Emergency and Organ Transplantation, Gastroenterology Section, University Hospital, Bari, Italy
| | - Raffaella Petrara
- Oncology and Immunology Section, AIDS Reference Center, Department of Oncology and Immunology, University of Padua, Padua, Italy
| | - Anita De Rossi
- Oncology and Immunology Section, AIDS Reference Center, Department of Oncology and Immunology, University of Padua, Padua, Italy
| | - Francesco Nudo
- Department of General Surgery and Organ Transplantation, Umberto I Policlinic, Sapienza University, Rome, Italy
| | - Luca Toti
- UOC Transplant Unit, Department of Surgery, Tor Vergata University, Rome, Italy
| | - Giovanni Fantola
- Department of Surgery, General and Hepatic Transplantation Surgery Unit, A.O.B. Brotzu, Cagliari, Italy
| | - Giovanni Vennarecci
- Division of General Surgery and Liver Transplantation, S. Camillo Hospital, Rome, Italy
| | | | - Antonio Daniele Pinna
- Liver and Multiorgan Transplant Unit, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Salvatore Gruttadauria
- Department of Gastroenterology and Hepatology, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), University of Pittsburgh Medical Center, Palermo, Italy
| | - Alfredo Di Leo
- Department of Emergency and Organ Transplantation, Gastroenterology Section, University Hospital, Bari, Italy
| | - Massimo Rossi
- Department of General Surgery and Organ Transplantation, Umberto I Policlinic, Sapienza University, Rome, Italy
| | - Giuseppe Tisone
- UOC Transplant Unit, Department of Surgery, Tor Vergata University, Rome, Italy
| | - Fausto Zamboni
- Department of Surgery, General and Hepatic Transplantation Surgery Unit, A.O.B. Brotzu, Cagliari, Italy
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Pierluca Piselli
- Department of Epidemiology, National Institute for Infectious Diseases L. Spallanzani, Rome, Italy
| | - Diego Serraino
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
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Pflüger MJ, Maurer MM, Hillebrandt KH, Andreou A, Geisel D, Schmelzle M, Pratschke J, Eurich D. Intrahepatic De Novo Tumors in Liver Recipients are Highly Associated With Recurrent Viral Hepatitis. J Clin Exp Hepatol 2021; 11:435-442. [PMID: 34276150 PMCID: PMC8267361 DOI: 10.1016/j.jceh.2020.11.003] [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: 08/28/2020] [Accepted: 11/16/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND/AIMS Long-term survival of liver transplant recipients is endangered by tumorigenesis at different sites. Little is known about primary de novo tumors developing in the graft. METHODS We analyzed the follow-up data of 2731 liver recipients that were transplanted between 1988 and 2019 at our institution (Charité - Universitätsmedizin Berlin, Department of Surgery). All cases with new intrahepatic tumors during follow-up were identified. RESULTS A total of nine patients were diagnosed at a median of 16 years (range, 2-24 years) after surgery. Eight patients presented with hepatocellular carcinoma (HCC), and one patient presented with epithelioid hemangioendothelioma (EHE). All eight HCC patients had a recurrence of the initial disease that had caused liver failure before transplantation. This was associated with viral reinfection with either HCV or HBV in seven cases. Of the nine patients, three underwent surgical resection and only one patient was alive at data abstraction. CONCLUSION Intrahepatic de novo neoplasms in the liver graft need to be considered in the long-term follow-up of liver recipients and were strongly associated with recurrent viral hepatitis in our study. Although prognosis of this rare complication is generally poor, patients may benefit from surgical resection of localized disease.
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Key Words
- AFP, alpha-fetoprotein
- ALF, acute liver failure
- CA 19-9, carbohydrate antigen 19-9
- CCA, cholangiocarcinoma
- CEA, carcinoembryonic antigen
- DCV, daclatasvir
- EHE, epithelioid hemangioendothelioma
- ESLD, end-stage liver disease
- HBIG, hepatitis B immune globulin
- HBsAg, hepatitis B surface antigen
- HCC, hepatocellular carcinoma
- IS, immunosuppressive therapy
- LT, liver transplantation
- NUCs, nucleos(t)ide analogues
- PSC, primary sclerosing cholangitis
- PTLD, post-transplantation lymphoproliferative disorder
- PegIFN, pegylated interferon
- RBV, ribavirin
- SOF, sofosbuvir
- SVR, sustained viral response
- epithelioid hemangioendothelioma
- hepatocellular carcinoma
- liver transplant
- long-term survival
- surgical resection
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Affiliation(s)
- Michael J. Pflüger
- Department of Surgery, Campus Charité Mitte
- Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany,Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Max M. Maurer
- Department of Surgery, Campus Charité Mitte
- Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
| | - Karl H. Hillebrandt
- Department of Surgery, Campus Charité Mitte
- Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
| | - Andreas Andreou
- Department of Surgery, Campus Charité Mitte
- Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany,Liver and Kidney Transplant Center, Inselspital – Bern University Hospital, Switzerland
| | - Dominik Geisel
- Department of Radiology (including Pediatric Radiology), Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
| | - Moritz Schmelzle
- Department of Surgery, Campus Charité Mitte
- Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
| | - Johann Pratschke
- Department of Surgery, Campus Charité Mitte
- Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
| | - Dennis Eurich
- Department of Surgery, Campus Charité Mitte
- Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany,Address for correspondence. Dr. Dennis Eurich, PD, Charité – Universitätsmedizin Berlin, Department of Surgery, Campus Virchow-Klinikum (CVK), Augustenburger Platz 1, 13353, Berlin, Germany.
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Choudhary NS, Saigal S, Saraf N, Soin AS. Extrahepatic Malignancies and Liver Transplantation: Current Status. J Clin Exp Hepatol 2021; 11:494-500. [PMID: 34276155 PMCID: PMC8267344 DOI: 10.1016/j.jceh.2020.10.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 10/20/2020] [Indexed: 12/12/2022] Open
Abstract
Recipients of liver transplantation (LT) remain at higher risk (adjusted for other risk factors) of de novo malignancies (DNMs). The higher risk can be attributed to the effect of immunosuppression and patient-related risk factors (age, tobacco, alcohol, etiology of liver disease). DNMs are an important cause of late mortality in liver transplant recipients. The pattern (type) of posttransplant malignancies reflects pattern in local population. The common types include skin cancers, solid organ malignancies, and post-transplant lymphoproliferative disorders. Counseling of patients about risk factors and surveillance protocols may help in the prevention and diagnosis at early stage. We also discuss the results of LT in patients with a history of extrahepatic malignancy in the pretransplant period.
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Affiliation(s)
| | - Sanjiv Saigal
- Address for correspondence: Dr Sanjiv Saigal DM, MRCP Senior Director, Hepatology and Liver Transplantation, Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Sector 38, Gurgaon, PIN 122001, India.
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Li S, Saviano A, Erstad DJ, Hoshida Y, Fuchs BC, Baumert T, Tanabe KK. Risk Factors, Pathogenesis, and Strategies for Hepatocellular Carcinoma Prevention: Emphasis on Secondary Prevention and Its Translational Challenges. J Clin Med 2020; 9:E3817. [PMID: 33255794 PMCID: PMC7760293 DOI: 10.3390/jcm9123817] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Revised: 11/11/2020] [Accepted: 11/17/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality globally. Given the limited therapeutic efficacy in advanced HCC, prevention of HCC carcinogenesis could serve as an effective strategy. Patients with chronic fibrosis due to viral or metabolic etiologies are at a high risk of developing HCC. Primary prevention seeks to eliminate cancer predisposing risk factors while tertiary prevention aims to prevent HCC recurrence. Secondary prevention targets patients with baseline chronic liver disease. Various epidemiological and experimental studies have identified candidates for secondary prevention-both etiology-specific and generic prevention strategies-including statins, aspirin, and anti-diabetic drugs. The introduction of multi-cell based omics analysis along with better characterization of the hepatic microenvironment will further facilitate the identification of targets for prevention. In this review, we will summarize HCC risk factors, pathogenesis, and discuss strategies of HCC prevention. We will focus on secondary prevention and also discuss current challenges in translating experimental work into clinical practice.
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Affiliation(s)
- Shen Li
- Division of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA 02114, USA; (S.L.); (D.J.E.); (B.C.F.)
| | - Antonio Saviano
- Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Université de Strasbourg, 67000 Strasbourg, France;
| | - Derek J. Erstad
- Division of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA 02114, USA; (S.L.); (D.J.E.); (B.C.F.)
| | - Yujin Hoshida
- Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Department of Internal Medicine, Dallas, TX 75390, USA;
| | - Bryan C. Fuchs
- Division of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA 02114, USA; (S.L.); (D.J.E.); (B.C.F.)
| | - Thomas Baumert
- Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Université de Strasbourg, 67000 Strasbourg, France;
| | - Kenneth K. Tanabe
- Division of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA 02114, USA; (S.L.); (D.J.E.); (B.C.F.)
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Four gene intrahepatic metastasis-risk signature predicts hepatocellular carcinoma malignant potential and early recurrence from intrahepatic metastasis. Surgery 2020; 169:903-910. [PMID: 33160638 DOI: 10.1016/j.surg.2020.09.032] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2019] [Revised: 09/16/2020] [Accepted: 09/30/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Hepatocellular carcinoma has a high recurrence rate even after curative surgery, and hepatocellular carcinoma risk-predictive biomarkers will enable identification of patients who most need close monitoring and cancer-preventive intervention. Hepatocellular carcinoma has 2 different recurrence patterns-a multicentric recurrence and an intrahepatic metastasis. We have reported that the molecular gene signature from the gene expression of adjacent liver can be used to predict multicentric recurrence of hepatocellular carcinoma, but the signature to predict recurrence from intrahepatic metastasis has not been established. We aimed to identify the recurrence from intrahepatic metastasis gene signature from the gene expression of tumor to predict recurrence from intrahepatic metastasis. METHODS The intrahepatic metastasis-risk signature was created based on the exhaustive analysis using a microarray transcriptome database of hepatocellular carcinoma. The intrahepatic metastasis-risk signature was measured in a cohort of 80 hepatocellular carcinoma patients, and the correlation with hepatocellular carcinoma recurrence and overall survival and each gene signature were analyzed and validated. RESULTS The gene signature assay classified the patients into high- (n = 20), intermediate- (n = 40), and low-risk (n = 20) groups. The high-risk prediction was independently associated with higher early hepatocellular carcinoma recurrence (hazard ratio = 3.7, P = .03) in multivariable modeling adjusted by tumor size, tumor number, and microvascular invasion. Gene set enrichment analysis demonstrates that the gene sets associated with "cell cycle" or "histone modulation" are highly enriched in the high intrahepatic metastasis gene signature group CONCLUSION: The intrahepatic metastasis gene signature predicts early recurrence and is associated with malignant potential related to the promoted cell cycle.
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Immunosuppressive regimens for adult liver transplant recipients in real-life practice: consensus recommendations from an Italian Working Group. Hepatol Int 2020; 14:930-943. [PMID: 33099753 PMCID: PMC7803715 DOI: 10.1007/s12072-020-10091-5] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 09/06/2020] [Indexed: 02/07/2023]
Abstract
It is a well-recognized fact that implementing new guidelines in clinical practice may be difficult; therefore the Italian Society for Organ and Tissue Transplantation (SITO) set out to define practical immunosuppression tools for the management of liver transplantation patients. In 2017, an Italian Working Group of liver transplant experts and hepatologists issued a set of consensus statements along with evidence-based recommendations on the use of everolimus after liver transplantation. This article presents the evidence- and consensus-based algorithms developed within the Italian Working Group, which are aimed towards guiding clinicians in the selection of immunosuppressive regimens for the management of adult liver transplant recipients in real-life practice. The liver transplant recipient population, typically managed in clinical practice, was divided into the following categories: (1) standard patients; (2) critically ill patients; (3) patients with a specific etiology; (4) patients with hepatocellular carcinoma; (5) and patients with de novo malignancies. The algorithms are divided into two parts, according to the time from transplantation (0-3 months and > 3 months) and are discussed here along with relevant supporting literature, when available. Ultimately, it is hoped that the evidence- and consensus-based algorithms developed within the Italian Working Group, and presented here, contribute to simplify, personalize, and optimize immunosuppression of liver transplantation recipients in clinical practice.
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Abstract
Cancer is an important cause of morbidity and mortality after liver transplantation and can occur through three mechanisms: recurrence of a recipient's pre-transplant malignancy, donor-related transmission and de novo development. Currently, the decision to list a patient with a history of malignancy is an individual one. Screening guidelines for potential donors and for recipients after transplant are still widely based on general population guidelines, while the role of chronic immunosuppression remains controversial. These shortcomings mean that patients present at diagnosis with advanced stages of the disease, often precluding curative treatments. The present review summarizes current recommendations for the screening of recipients and donors for pre- and post-transplant malignancies, and current management of recipients who develop cancer after a liver transplant.
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Di Maira T, Little EC, Berenguer M. Immunosuppression in liver transplant. Best Pract Res Clin Gastroenterol 2020; 46-47:101681. [PMID: 33158467 DOI: 10.1016/j.bpg.2020.101681] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Accepted: 08/31/2020] [Indexed: 02/07/2023]
Abstract
The increasing potency of immunosuppression (IS) agents resulted in significantly decreased rates of steroid resistant rejection and rejection related graft loss in liver transplantation (LT). Currently, more than two thirds of late mortality after LT is unrelated to graft function. However, the increased benefit of more potent IS drugs, coupled with the prolonged survival of transplant recipients led to longer patients exposure to these drugs and their unwanted adverse effects, creating a double-edged sword. In this article the authors describe the mechanism of action and the adverse effects of the most commonly used immunosuppressed drugs, and the most commonly used IS regimens for both induction and maintenance regimens. The balance between the ideal IS regimen to prevent rejection and the need to minimize the dose of IS drugs in order to prevent the adverse effects related to its use requires the knowledge of the science and the experience with the art of medicine. The different protocols aimed at protecting renal function and preventing the development of de novo cancer and metabolic syndrome are discussed here. The main causes of mortality late after liver transplant are associated with prolonged use of IS medications, and clear evidence exists about over-immunosuppression of recipients of liver transplant. The current status of strategies of IS minimization and withdrawal are reviewed in this article, with evaluation of its benefits and pitfalls.
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Affiliation(s)
- Tommaso Di Maira
- Liver Transplantation and Hepatology Unit, Hospital Universitari I Politècnic La Fe, Avda Fernando Abril Martorell, 106 (Torre F5), Valencia, 46026, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, 28029, Spain; ISS La Fe, Valencia, 46026, Spain.
| | - Ester Coelho Little
- University of Arizona, College of Medicine, 3110 East Minnesona Avenue, Phoenix, AZ, 85016, USA.
| | - Marina Berenguer
- Liver Transplantation and Hepatology Unit, Hospital Universitari I Politècnic La Fe, Avda Fernando Abril Martorell, 106 (Torre F5), Valencia, 46026, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, 28029, Spain; ISS La Fe, Valencia, 46026, Spain; Universidad de Valencia, Facultad de Medicina, Valencia, 46010, Spain.
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Gitto S, Aspite S, Golfieri L, Caputo F, Vizzutti F, Grandi S, Patussi V, Marra F. Alcohol use disorder and liver transplant: new perspectives and critical issues. Korean J Intern Med 2020; 35:797-810. [PMID: 32241080 PMCID: PMC7373982 DOI: 10.3904/kjim.2019.409] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Accepted: 03/03/2020] [Indexed: 12/13/2022] Open
Abstract
Alcoholic liver disease is a consolidated indication for liver transplantation, but many unsolved issues can be highlighted. Patients with alcohol use disorder develop peculiar comorbidities that can become contraindications for transplantation. Moreover, a number of social and psychological patterns should be evaluated to select candidates with a low risk of alcohol relapse and adequate post-transplant adherence. In this context, the 6-month rule is too rigid to be widely applied. A short period of abstinence (1 to 3 months) is useful to estimate recovery of liver function and, possibly to avoid transplant. Cardiovascular disorders and extra-hepatic malignancies represent the main clinical issues after transplant. Patients transplanted due to alcoholic disease are a major risk for other liver diseases. Severe corticosteroid-resistant alcoholic acute hepatitis is a debated indication for transplant. However, available data indicate that well-selected patients have excellent post-transplant outcomes. Behavioral therapy, continued psychological support and a multidisciplinary team are essential to achieve and maintain complete alcohol abstinence during the transplant process. Alcoholic liver disease is an excellent indication for a liver transplant but patients with alcohol use disorder deserve a personalized approach and dedicated resources.
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Affiliation(s)
- Stefano Gitto
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Silvia Aspite
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Lucia Golfieri
- Department of Psychology, University of Bologna, Bologna, Italy
| | - Fabio Caputo
- Department of Internal Medicine, SS Annunziata Hospital, University of Ferrara, Cento, Italy
| | - Francesco Vizzutti
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Silvana Grandi
- Department of Psychology, University of Bologna, Bologna, Italy
| | | | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
- Research Center Denothe, University of Florence, Italy
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Nogueras López F, Espinosa Aguilar MD, Abellán Alfocea P, Ortega Suazo EJ, González Sánchez M, Redondo Cerezo E, López Garrido MA. Descriptive Analysis of Everolimus Conversion in Liver Transplant Recipients With Malignant Neoplastic Disease. Transplant Proc 2020; 52:553-555. [PMID: 32035682 DOI: 10.1016/j.transproceed.2019.12.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Revised: 11/14/2019] [Accepted: 12/06/2019] [Indexed: 01/15/2023]
Abstract
BACKGROUND Calcineurin inhibitors are associated with the development of de novo tumors and increased recurrence of hepatocellular carcinoma after liver transplant. It has been suggested that mammalian target of rapamycin inhibitors (everolimus [EVR]) may improve prognosis. We analyzed our experience on the use of EVR in malignant neoplasms in liver transplantation. METHODS We performed a retrospective descriptive analysis of 477 transplants performed between 2002 and 2019 at Virgen de las Nieves Hospital. A total of 100 patients received EVR; 23 transplants were because of tumor disease (23%), with de novo tumor in 12 patients and hepatocarcinoma in 11. The statistical study was carried out using the statistical program SPSS 17.0 software. RESULTS The study included 18 male patients (78.3%) and 5 female patients (21.7%) with an average age of 59.67 years. The most common indications of liver transplant have been alcoholic cirrhosis in 39% and hepatitis C virus cirrhosis in 21.7%. De novo tumors were lung neoplasm in 4 patients (33.3%), lymphoma in 2 patients(16.7%), oropharynx in 2 patients (16.7%), skin tumors in 2 patients (16.7%), and a kidney tumor (8.3%) in 1 patient. As for hepatocellular carcinoma, 8 patients met Milan criteria on the explant (61.5%). Tacrolimus was discontinued in all cases. The average onset time of post-transplant EVR was 2231.42 days in the de novo neoplasms and 307.45 days in those receiving transplants because of hepatocellular carcinoma (P = .05). We observed 5 deaths (21.7%). CONCLUSION Although the beneficial long-term role of EVR in liver transplant recipients with tumor disease is not demonstrated, it is used by most transplant units, both in de novo neoplasms and those receiving transplants because of hepatocellular carcinoma.
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Affiliation(s)
- Flor Nogueras López
- Hepatology Department, Virgen de las Nieves University Hospital, Granada, Spain.
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Toward Zero Hepatitis C Virus-Related Mortality as a Prerequisite for the Release of Resources in a Center for Follow-up of Liver Transplant. Transplant Proc 2019; 51:2958-2961. [PMID: 31629537 DOI: 10.1016/j.transproceed.2019.04.093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Accepted: 04/13/2019] [Indexed: 11/23/2022]
Abstract
Taking charge of a liver transplanted (LT) patient implies not only to follow up the transplanted organ (eg, immunosuppression and cancer risk) but also to deal with the prevailing patient's active problems. The recurrence of hepatitis C on the graft has historically been one of the main active problems to be addressed, leading to 30% to 40% mortality per se in these patients and has involved many resources in the hepatological centers responsible for the follow-up. We verified how much the availability of the new drugs with direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) has impacted the mortality within the assisted population, changing its characteristics and addressing new clinical issues in the LT-patients. We performed a retrospective comparison between 230 LT patients followed up during pre-DAA era (group 1, with 88 HCV RNA-positive) and 244 patients observed from 2014 onward when DAAs became available (group 2, with 79 HCV RNA-positive). Fifty-two antiviral therapies were performed in group 1 with 18 sustained virologic response (SVR) (35%) and 53 treatments, of which 37 were retreatments, in group 2 with 51 SVR (96%), P = .0001. Deaths for HCV-related causes were 19 of 33 (57%) in group 1 and 7 of 24 (24%) in group 2, P = .01. The Kaplan-Meier showed a dramatic reduction in excess mortality in HCV-LT patients after the availability of DAAs. These results suggest that HCV is no longer the main active problem of follow-up in liver transplants, therefore the resources can be relocated to take care of other clinical aspects.
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Manzia TM, Angelico R, Gazia C, Lenci I, Milana M, Ademoyero OT, Pedini D, Toti L, Spada M, Tisone G, Baiocchi L. De novo malignancies after liver transplantation: The effect of immunosuppression-personal data and review of literature. World J Gastroenterol 2019; 25:5356-5375. [PMID: 31558879 PMCID: PMC6761240 DOI: 10.3748/wjg.v25.i35.5356] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Revised: 08/08/2019] [Accepted: 08/24/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Immunosuppression has undoubtedly raised the overall positive outcomes in the post-operative management of solid organ transplantation. However, long-term exposure to immunosuppression is associated with critical systemic morbidities. De novo malignancies following orthotopic liver transplants (OLTs) are a serious threat in pediatric and adult transplant individuals. Data from different experiences were reported and compared to assess the connection between immunosuppression and de novo malignancies in liver transplant patients. AIM To study the role of immunosuppression on the incidence of de novo malignancies in liver transplant recipients. METHODS A systematic literature examination about de novo malignancies and immunosuppression weaning in adult and pediatric OLT recipients was described in the present review. Worldwide data were collected from highly qualified institutions performing OLTs. Patient follow-up, immunosuppression discontinuation and incidence of de novo malignancies were reported. Likewise, the review assesses the differences in adult and pediatric recipients by describing the adopted immunosuppression regimens and the different type of diagnosed solid and blood malignancy. RESULTS Emerging evidence suggests that the liver is an immunologically privileged organ able to support immunosuppression discontinuation in carefully selected recipients. Malignancies are often detected in liver transplant patients undergoing daily immunosuppression regimens. Post-transplant lymphoproliferative diseases and skin tumors are the most detected de novo malignancies in the pediatric and adult OLT population, respectively. To date, immunosuppression withdrawal has been achieved in up to 40% and 60% of well-selected adult and pediatric recipients, respectively. In both populations, a clear benefit of immunosuppression weaning protocols on de novo malignancies is difficult to ascertain because data have not been specified in most of the clinical experiences. CONCLUSION The selected populations of tolerant pediatric and adult liver transplant recipients greatly benefit from immunosuppression weaning. There is still no strong clinical evidence on the usefulness of immunosuppression withdrawal in OLT recipients on malignancies. An interesting focus is represented by the complete reconstitution of the immunological pathways that could help in decreasing the incidence of de novo malignancies and may also help in treating liver transplant patients suffering from cancer.
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Affiliation(s)
- Tommaso Maria Manzia
- HPB and Transplant Unit, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | - Roberta Angelico
- Division of Abdominal Transplantation and HPB Surgery, Bambino Gesù Children's Hospital IRCCS, Rome 00165, Italy
| | - Carlo Gazia
- HPB and Transplant Unit, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
- Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC 27101, United States
| | - Ilaria Lenci
- Hepatology and Liver Transplant Unit, University of Tor Vergata, Rome 00133, Italy
| | - Martina Milana
- Hepatology and Liver Transplant Unit, University of Tor Vergata, Rome 00133, Italy
| | | | - Domiziana Pedini
- Division of Abdominal Transplantation and HPB Surgery, Bambino Gesù Children's Hospital IRCCS, Rome 00165, Italy
| | - Luca Toti
- HPB and Transplant Unit, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | - Marco Spada
- Division of Abdominal Transplantation and HPB Surgery, Bambino Gesù Children's Hospital IRCCS, Rome 00165, Italy
| | - Giuseppe Tisone
- HPB and Transplant Unit, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | - Leonardo Baiocchi
- Hepatology and Liver Transplant Unit, University of Tor Vergata, Rome 00133, Italy
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Garg R, Kaul S, Arora D, Kashyap V. Posttransplant epithelioid inflammatory myofibroblastic sarcoma: A case report. INDIAN J PATHOL MICR 2019; 62:303-305. [PMID: 30971562 DOI: 10.4103/ijpm.ijpm_284_17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare entity and a novel variant of inflammatory myofibroblastic tumor (IMT), usually seen in children and nonsmoking young adults. Their occurrence in a posttransplant setting is still rare. These tumors are characterized by prominent epithelioid morphology, large histiocytoid "Reed Sternberg"-like cell, unique pattern of ALK immuno-reactivity, and aggressive clinical behavior. Their etiology and metastatic potential is controversial. In a post-transplant setting, many factors such as trauma, infections with EBV, HIV, Hepatitis C, mycobacteria, fungus, and chemotherapy-induced immunosuppression have been implicated in their etiology. We present the case of a 2-year-old female child who developed multiple omental and mesenteric tumor nodules, 8 months post liver transplant for progressive familial intrahepatic cholestasis (PFIC). Following a histopathological diagnosis of "mesenchymal neoplasm of possible malignant nature" on a trucut biopsy and frozen section, tumor debulking was performed. A final histological diagnosis of EMIS was made on the completely resected tumor. The patient remains in remission nearly 7 months after presentation, without any follow-up systemic chemotherapy. IMT after a solid organ transplant is rare, only 5 cases have been reported in the literature until now. Similar phenomenon has also been noted with hematopoietic stem cell transplant. However, to our knowledge, this case of EMIS in a post liver transplant patient is first of its kind.
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Affiliation(s)
- Ritu Garg
- Department of Histopathology, Apollo Hospital, New Delhi, India
| | - Sumaid Kaul
- Department of Histopathology, Apollo Hospital, New Delhi, India
| | | | - Vikas Kashyap
- Department of Histopathology, Apollo Hospital, New Delhi, India
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Long-term care of transplant recipients: de novo neoplasms after liver transplantation. Curr Opin Organ Transplant 2019; 23:187-195. [PMID: 29324517 DOI: 10.1097/mot.0000000000000499] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE OF REVIEW Since the first liver transplantation in the early 1960s, there have been significant improvements in the recipients' long-term outcome. Patients who have undergone transplantation are exposed to a high risk of developing neoplastic disease, not only because of their chronic immunosuppression, but also related to physiological aging, lifestyle, chronic viral infections, liver disease cause, and carcinogenic immunosuppressants. The present review covers the latest and most relevant data on de novo neoplasms after liver transplantation, and discusses their implications for clinical practice. RECENT FINDINGS Given the impact of de novo neoplasms, in terms of morbidity and mortality, transplant teams must be prepared to diagnose and treat these conditions promptly. Dedicated cancer screening protocols are warranted. Although surveillance strategies are based on data concerning the general population, they should be customized in the light of each transplant recipient's risk factors. The resulting risk stratification is crucially important to the design of early intervention programs, and for addressing the modulation of individualized immunosuppressive regimens. SUMMARY De novo malignancies are a significant issue for the liver transplant population, but targeted screening programs have shown that survival rates similar to those of nonimmunosuppressed patients can be achieved. New oncological surveillance strategies covering the prophylaxis, monitoring, and treatment of de novo neoplasms should take high priority in clinical research.
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Losurdo G, Ingravallo G, Mongelli A, Castellaneta NM, Pisani A. Unexpected mediastinal mass in a liver transplanted patient. Hepatobiliary Pancreat Dis Int 2019; 18:199-201. [PMID: 30558839 DOI: 10.1016/j.hbpd.2018.11.005] [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: 08/04/2018] [Accepted: 11/07/2018] [Indexed: 02/05/2023]
Affiliation(s)
- Giuseppe Losurdo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University "Aldo Moro", Piazza G. Cesare 11, 70124 Bari, Italy
| | - Giuseppe Ingravallo
- Section of Pathology, Department of Emergency and Organ Transplantation, University "Aldo Moro", Piazza G. Cesare 11, 70124 Bari, Italy
| | - Antonio Mongelli
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University "Aldo Moro", Piazza G. Cesare 11, 70124 Bari, Italy
| | - Nicola Maurizio Castellaneta
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University "Aldo Moro", Piazza G. Cesare 11, 70124 Bari, Italy
| | - Antonio Pisani
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University "Aldo Moro", Piazza G. Cesare 11, 70124 Bari, Italy.
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Totally Laparoscopic Distal Gastrectomy in Post Liver Transplant Patient. THE JOURNAL OF MINIMALLY INVASIVE SURGERY 2019; 22:39-42. [PMID: 35601701 PMCID: PMC9007717 DOI: 10.7602/jmis.2019.22.1.39] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Revised: 07/12/2018] [Accepted: 07/13/2018] [Indexed: 11/21/2022]
Abstract
The risk of malignancy after transplantation is higher than that of general population. Laparoscopic surgery has become a standard treatment of gastric cancer. However, there are no case reports evaluating totally laparoscopic gastrectomy in patients with previous liver transplantation. Herein we report our experience with a liver transplant recipient who underwent totally laparoscopic distal gastrectomy (TLDG) for gastric cancer. A 63 year-old man underwent orthotopic liver transplantation (OLT) for cryptogenic liver cirrhosis. 8 years later, gastric cancer was diagnosed during the follow-up. Endoscopic submucosal dissection was performed and additional surgical resection was needed. TLDG and D1+ lymph node dissection was performed, and the patient was discharged on the 8th post-operative day without any complications. To the best of our knowledge, this is the first case of de novo gastric cancer treated with TLDG after OLT. This suggests that TLDG is a feasible for patients after OLT.
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Mora-Ortiz M, Trichard M, Oregioni A, Claus SP. Thanatometabolomics: introducing NMR-based metabolomics to identify metabolic biomarkers of the time of death. Metabolomics 2019; 15:37. [PMID: 30834988 PMCID: PMC6476858 DOI: 10.1007/s11306-019-1498-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Accepted: 02/21/2019] [Indexed: 01/15/2023]
Abstract
INTRODUCTION Death is the permanent cessation of the critical functions of the organism as a whole. However, the shutdown of a complex biological organism does not abruptly terminate at time of death. New high-throughput technologies allow the systematic investigation of the biochemical modulations occurring after death. Recent genomics studies have demonstrated that genes remain active after death, triggering upregulation of some genes and initiating feedback loops. These genes were mostly involved in pathways related to immunity, inflammation and cancer. These genetic modulations suggest many biochemical events persist after death, which can be captured using a metabolomics approach. OBJECTIVES This proof of concept work aimed to determine whether NMR spectroscopy could identify metabolomics changes occurring after death, and characterise the nature of these metabolomics modulations. METHODS High-resolution 1H-NMR spectroscopy was applied to six biological matrices: heart, kidney, liver, spleen, skin and white adipose tissue of ten adult mice at three different type points. RESULTS Forty-three metabolites were associated with post mortem metabolomics modulations. Kidney, heart and spleen showed the highest metabolic perturbations. Conversely, skin and white adipose tissue were the least altered matrices. Early metabolic modulations were associated with energy metabolism and DNA synthesis, by contrast, late metabolomics modulations were associated with microbial metabolism. CONCLUSIONS NMR has proven potential to determine the time of death based on post-mortem metabolomics modulations. This could be useful in the context of transplants, forensic studies and as internal quality control in metabolomics studies. Further investigations are required to validate these findings in humans in order to determine which compounds robustly reflect post-mortem metabolic fluctuations to accurately determine the time of death.
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Affiliation(s)
- Marina Mora-Ortiz
- Department of Food and Nutritional Sciences, The University of Reading, Whiteknights Campus, Reading, RG6 6AP, UK.
- Department of Twin Research, Kings College London, St Thomas' Hospital Campus, 3rd Floor South Wing Block D, Westminster Bridge Road, London, SE1 7EH, UK.
| | - Marianne Trichard
- Département Biologie Alimentaire à l'Ecole Nationale Supérieure de Chimie, Biologie et Physique de Bordeaux (ENSCBP), 33600, Pessac, France
| | - Alain Oregioni
- MRC Biomedical NMR Centre, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK
| | - Sandrine P Claus
- Department of Food and Nutritional Sciences, The University of Reading, Whiteknights Campus, Reading, RG6 6AP, UK
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How to Improve Compliance With Dermatologic Screening in Liver Transplant Recipients: Experience in a (Spoke) Peripheral Center for Follow-up. Transplant Proc 2019; 51:184-186. [DOI: 10.1016/j.transproceed.2018.02.215] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Accepted: 02/06/2018] [Indexed: 01/10/2023]
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Athuluri-Divakar SK, Hoshida Y. Generic chemoprevention of hepatocellular carcinoma. Ann N Y Acad Sci 2018; 1440:23-35. [PMID: 30221358 DOI: 10.1111/nyas.13971] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Revised: 08/21/2018] [Accepted: 08/24/2018] [Indexed: 02/06/2023]
Abstract
Chronic fibrotic liver disease caused by viral or metabolic etiologies is a high-risk condition for developing hepatocellular carcinoma (HCC). Even after curative treatment of early-stage HCC tumor, the carcinogenic microenvironment persists in the remnant diseased liver and supports the development of de novo HCC tumors (de novo HCC recurrence). Therefore, prevention of HCC development in patients at risk of not only first-primary but also second-primary HCC tumors is theoretically the most impactful strategy to improve patient prognosis. However, no such therapy has been established to date. One major challenge is the identification of clinically relevant targets that can be achieved by utilizing the reverse-engineering strategy of chemoprevention discovery, which integrates omics information from clinical cohorts with completed follow-up for cancer development. Clinical and experimental studies have suggested etiology-specific and generic candidate HCC chemoprevention strategies, including statins, antidiabetic drugs, selective molecular targeted agents, and dietary and nutritional substances. Clinical testing of the candidate compounds can be cost-effectively performed by combining it with HCC risk biomarker evaluation to specify the target patient population most likely to benefit from the therapy. Nontoxic, generic agents will have broad clinical applicability across the diverse HCC etiologies and clinical contexts and are expected to substantially improve the still dismal prognosis of HCC.
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Affiliation(s)
- Sai Krishna Athuluri-Divakar
- Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Yujin Hoshida
- Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
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Åberg F, Isoniemi H, Pukkala E, Jalanko H, Rasmussen A, Storm HH, Schultz N, Bennet W, Ekvall N, Ericzon BG, Malenicka S, Tretli S, Line PD, Boberg KM, Østensen A, Karlsen TH, Nordin A. Cancer After Liver Transplantation in Children and Young Adults: A Population-Based Study From 4 Nordic Countries. Liver Transpl 2018; 24:1252-1259. [PMID: 30120902 DOI: 10.1002/lt.25305] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2018] [Accepted: 06/19/2018] [Indexed: 02/07/2023]
Abstract
Cancer after liver transplantation (LT) constitutes a threat also for young recipients, but cancer risk factors are usually absent in children and large studies on the cancer risk profile in young LT recipients are scarce. Data of patients younger than 30 years who underwent LT during the period 1982-2013 in the Nordic countries were linked with respective national cancer registries to calculate standardized incidence ratios (SIRs). A total of 37 cancer cases were observed in 923 patients with 7846 person-years of follow-up. The SIR for all cancer types, compared with the matched general population, was 9.8 (12.4 for males and 7.8 for females). Cumulative incidence of cancer adjusted for the competing risk of death was 2% at 10 years, 6% at 20 years, and 22% at 25 years after LT. Non-Hodgkin lymphoma was the most common cancer type (n = 14) followed by colorectal (n = 4) and hepatocellular cancer (n = 4). Age was a significant risk factor for cancer, and the absolute risk of most cancers (except for lymphoma) increased considerably in young adults older than 20 years. The cancer risk pattern is different in pediatric and young LT patients compared with adult recipients. The striking increase in cancer incidence in young adulthood after the second decade of life deserves further consideration in transition programs.
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Affiliation(s)
- Fredrik Åberg
- Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland
| | - Helena Isoniemi
- Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland
| | - Eero Pukkala
- Institute for Statistical and Epidemiological Cancer Research, Finnish Cancer Registry, Helsinki, Finland
- Faculty of Social Sciences, University of Tampere, Tampere, Finland
| | - Hannu Jalanko
- Department of Pediatric Nephrology and Transplantation, Children's Hospital, Helsinki University Hospital, Helsinki, Finland
| | - Allan Rasmussen
- Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | | | - Nicolai Schultz
- Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - William Bennet
- Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Nils Ekvall
- Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg and Queen Silvia Children's Hospital, Gothenburg, Sweden
| | - Bo-Göran Ericzon
- Division of Transplantation Surgery, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Silvia Malenicka
- Department of Pediatrics, Astrid Lindgren's Children's Hospital Huddinge, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | | | - Pål-Dag Line
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Kirsten Muri Boberg
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
| | - Anniken Østensen
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway
| | - Tom Hemming Karlsen
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
- Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Arno Nordin
- Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland
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Gitto S, de Maria N, di Benedetto F, Tarantino G, Serra V, Maroni L, Cescon M, Pinna AD, Schepis F, Andreone P, Villa E. De-novo nonalcoholic steatohepatitis is associated with long-term increased mortality in liver transplant recipients. Eur J Gastroenterol Hepatol 2018; 30:766-773. [PMID: 29505475 DOI: 10.1097/meg.0000000000001105] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Patients who have undergone transplantation often develop metabolic syndrome (MetS) and de-novo nonalcoholic fatty liver disease (NAFLD). Our aim was to evaluate the impact of metabolic disease on cardiovascular and neoplastic risk and survival. PATIENTS AND METHODS Data from patients who underwent transplantation between 2000 and 2005 in two Italian transplant centers were analyzed. Cox regression analysis was carried out for predictors of de-novo NAFLD and nonalcoholic steatohepatitis (NASH), cardiovascular events, de-novo extrahepatic cancers, and survival. Survival analysis was completed using the Kaplan-Meier method. A P value less than 0.05 was considered significant for all tests. RESULTS De-novo NAFLD was found in one-fifth of 194 patients. Patients with de-novo NAFLD fulfilled the criteria of MetS in 74.4% of cases, while patients without de-novo NAFLD in 29.8% (P=0.000). On multivariate analysis, MetS correlated independently with de-novo NAFLD and this emerged as an independent predictor of cardiovascular events and as a relevant risk factor for solid extrahepatic cancer. Data on smoking habits, which represent a consolidated risk factor for cardiovascular events and cancer in both the general population and patients who have undergone transplantation, are not available. In the subset of histologically proven NASH, it was the strongest predictor of long-term survival (hazard ratio=4.133, 95% confidence interval: 1.385-12.331, P=0.011). CONCLUSION Post-transplant NAFLD represented a strong risk factor for cardiovascular atherosclerotic disease and solid extrahepatic cancer, whereas de novo histologically proven NASH was an independent predictor of long-term mortality.
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Affiliation(s)
- Stefano Gitto
- Department of Gastroenterology, Policlinico of Modena University Hospital of Modena
| | - Nicola de Maria
- Department of Gastroenterology, Policlinico of Modena University Hospital of Modena
| | - Fabrizio di Benedetto
- Department of Surgery and Liver Transplant, Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena
| | - Giuseppe Tarantino
- Department of Surgery and Liver Transplant, Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena
| | - Valentina Serra
- Department of Surgery and Liver Transplant, Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena
| | - Lorenzo Maroni
- General Surgery and Transplant Unit, Department of Medical and Surgical Sciences
| | - Matteo Cescon
- General Surgery and Transplant Unit, Department of Medical and Surgical Sciences
| | - Antonio D Pinna
- General Surgery and Transplant Unit, Department of Medical and Surgical Sciences
| | - Filippo Schepis
- Department of Gastroenterology, Policlinico of Modena University Hospital of Modena
| | - Pietro Andreone
- Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, ITEC Unit, University of Bologna, Bologna, Italy
| | - Erica Villa
- Department of Gastroenterology, Policlinico of Modena University Hospital of Modena
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Nordin A, Åberg F, Pukkala E, Pedersen CR, Storm HH, Rasmussen A, Bennet W, Olausson M, Wilczek H, Ericzon BG, Tretli S, Line PD, Karlsen TH, Boberg KM, Isoniemi H. Decreasing incidence of cancer after liver transplantation-A Nordic population-based study over 3 decades. Am J Transplant 2018; 18:952-963. [PMID: 28925583 DOI: 10.1111/ajt.14507] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Revised: 08/11/2017] [Accepted: 09/07/2017] [Indexed: 01/25/2023]
Abstract
Cancer remains one of the most serious long-term complications after liver transplantation (LT). Data for all adult LT patients between 1982 and 2013 were extracted from the Nordic Liver Transplant Registry. Through linkage with respective national cancer-registry data, we calculated standardized incidence ratios (SIRs) based on country, sex, calendar time, and age-specific incidence rates. Altogether 461 cancers were observed in 424 individuals of the 4246 LT patients during a mean 6.6-year follow-up. The overall SIR was 2.22 (95% confidence interval [CI], 2.02-2.43). SIRs were especially increased for colorectal cancer in recipients with primary sclerosing cholangitis (4.04) and for lung cancer in recipients with alcoholic liver disease (4.96). A decrease in the SIR for cancers occurring within 10 years post-LT was observed from the 1980s: 4.53 (95%CI, 2.47-7.60), the 1990s: 3.17 (95%CI, 2.70-3.71), to the 2000s: 1.76 (95%CI, 1.51-2.05). This was observed across age- and indication-groups. The sequential decrease for the SIR of non-Hodgkin lymphoma was 25.0-12.9-7.53, and for nonmelanoma skin cancer 80.0-29.7-10.4. Cancer risk after LT was found to be decreasing over time, especially for those cancers that are strongly associated with immunosuppression. Whether immunosuppression minimization contributed to this decrease merits further study.
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Affiliation(s)
- A Nordin
- Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland
| | - F Åberg
- Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland
| | - E Pukkala
- Finnish Cancer Registry - Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland
- Faculty of Social Sciences, University of Tampere, Tampere, Finland
| | - C R Pedersen
- Department of Surgery and Transplantation, Rigshospitalet, Copenhagen, Denmark
| | - H H Storm
- Danish Cancer Society, Copenhagen, Denmark
| | - A Rasmussen
- Department of Surgery and Transplantation, Rigshospitalet, Copenhagen, Denmark
| | - W Bennet
- Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - M Olausson
- Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - H Wilczek
- Division of Transplantation Surgery, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - B-G Ericzon
- Division of Transplantation Surgery, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - S Tretli
- The Norwegian Cancer Registry, Oslo, Norway
| | - P-D Line
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - T H Karlsen
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - K M Boberg
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - H Isoniemi
- Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland
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Fujiwara N, Friedman SL, Goossens N, Hoshida Y. Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine. J Hepatol 2018; 68:526-549. [PMID: 28989095 PMCID: PMC5818315 DOI: 10.1016/j.jhep.2017.09.016] [Citation(s) in RCA: 520] [Impact Index Per Article: 74.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Revised: 09/24/2017] [Accepted: 09/25/2017] [Indexed: 01/27/2023]
Abstract
Patients who develop chronic fibrotic liver disease, caused by viral or metabolic aetiologies, are at a high risk of developing hepatocellular carcinoma (HCC). Even after complete HCC tumour resection or ablation, the carcinogenic tissue microenvironment in the remnant liver can give rise to recurrent de novo HCC tumours, which progress into incurable, advanced-stage disease in most patients. Thus, early detection and prevention of HCC development is, in principle, the most impactful strategy to improve patient prognosis. However, a "one-size-fits-all" approach to HCC screening for early tumour detection, as recommended by clinical practice guidelines, is utilised in less than 20% of the target population, and the performance of screening modalities, including ultrasound and alpha-fetoprotein, is suboptimal. Furthermore, optimal screening strategies for emerging at-risk patient populations, such as those with chronic hepatitis C after viral cure, or those with non-cirrhotic, non-alcoholic fatty liver disease remain controversial. New HCC biomarkers and imaging modalities may improve the sensitivity and specificity of HCC detection. Clinical and molecular HCC risk scores will enable precise HCC risk prediction followed by tailoured HCC screening of individual patients, maximising cost-effectiveness and optimising allocation of limited medical resources. Several aetiology-specific and generic HCC chemoprevention strategies are evolving. Epidemiological and experimental studies have identified candidate chemoprevention targets and therapies, including statins, anti-diabetic drugs, and selective molecular targeted agents, although their clinical testing has been limited by the lengthy process of cancer development that requires long-term, costly studies. Individual HCC risk prediction is expected to overcome the challenge by enabling personalised chemoprevention, targeting high-risk patients for precision HCC prevention and substantially improving the dismal prognosis of HCC.
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Affiliation(s)
- Naoto Fujiwara
- Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, USA; Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Japan
| | - Scott L Friedman
- Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, USA
| | - Nicolas Goossens
- Division of Gastroenterology and Hepatology, Geneva University Hospital, Geneva, Switzerland
| | - Yujin Hoshida
- Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, USA.
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48
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Torres-Landa S, Muñoz-Abraham AS, Fortune BE, Gurung A, Pollak J, Emre SH, Rodriguez-Davalos MI, Schilsky ML. De-novo hepatocellular carcinoma after pediatric living donor liver transplantation. World J Hepatol 2017; 9:1361-1366. [PMID: 29359020 PMCID: PMC5756726 DOI: 10.4254/wjh.v9.i36.1361] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2017] [Revised: 11/22/2017] [Accepted: 12/07/2017] [Indexed: 02/06/2023] Open
Abstract
De-novo malignancies carry an incidence ranging between 3%-26% after transplant and account for the second highest cause of post-transplant mortality behind cardiovascular disease. While the majority of de-novo malignancies after transplant usually consist of skin cancers, there has been an increasing rate of solid tumor cancers over the last 15 years. Although, recurrence of hepatocellular carcinoma (HCC) is well understood among patients transplanted for HCC, there are increasing reports of de-novo HCC in those transplanted for a non-HCC indication. The proposed pathophysiology for these cases has been mainly connected to the presence of advanced graft fibrosis or cirrhosis and always associated with the presence of hepatitis B or C virus. We report the first known case of de-novo HCC in a recipient, 14 years after a pediatric living related donor liver transplantation for end-stage liver disease due to biliary atresia without the presence of hepatitis B or C virus before and after transplant. We present this case report to increase the awareness of this phenomenon and address on the utility for screening and surveillance of hepatocellular carcinoma among these individuals. One recommendation is to use similar guidelines for screening, diagnosis, and treatment for HCC as those used for primary HCC in the pre-transplant patient, focusing on those recipients who have advanced fibrosis in the allograft, regardless of etiology.
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Affiliation(s)
- Samuel Torres-Landa
- Department of Gastrointestinal Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, United States
| | | | - Brett E Fortune
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY 10021, United States
| | - Ananta Gurung
- Department of Pathology, Royal Columbian Hospital, New Westminster, British Columbia V3L 3W7, Canada
| | - Jeffrey Pollak
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06510, United States
| | - Sukru H Emre
- Department of Surgery, Yale University School of Medicine, New Haven, CT 06510, United States
| | | | - Michael L Schilsky
- Division of Digestive Diseases and Transplant and Immunology, Department of Medicine and Surgery, Yale University School of Medicine, New Haven, CT 06510, United States
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49
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Sposito C, Droz Dit Busset M, Citterio D, Bongini M, Mazzaferro V. The place of liver transplantation in the treatment of hepatic metastases from neuroendocrine tumors: Pros and cons. Rev Endocr Metab Disord 2017; 18:473-483. [PMID: 29359266 DOI: 10.1007/s11154-017-9439-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Liver metastases occur in nearly half of NET patients (MNETs) and heavily affect prognosis, with 5-yr. OS around 19-38%. Although it is difficult to show outcome differences for available treatments, due to the long course of disease, surgery for MNETs remains the most effective option in terms of survival and symptom control. Since MNETs frequently present as an oligo-metastatic, liver-limited disease, unresectable in 80% of cases, liver transplantation (LT) has emerged as a potential curative treatment. Nevertheless, experience with LT for MNETs is limited and burdened by highly heterogeneous outcomes and significant recurrence rate, mostly explained by the variability of selection criteria. Several prognostic factors have been identified: extended surgery on primary tumor associated to LT, elderly patients, pancreatic primary (pNET), extensive liver involvement, poorly differentiated tumors, high Ki67 levels and short wait time to LT. A proper patients' selection based on these data (Milan NET criteria) allows a significant survival advantage over non-transplant strategies, with excellent outcomes in recent series (69-97.2% 5-yr. OS) as opposed to patients undergoing non-surgical treatments (34-50.9%). Evidence indicates LT as the best option for selected patients with MNETs. The use of organs for MNETs is therefore justified.
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Affiliation(s)
- Carlo Sposito
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy
| | - Michele Droz Dit Busset
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy
| | - Davide Citterio
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy
| | - Marco Bongini
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy
| | - Vincenzo Mazzaferro
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy.
- University of Milan, Milan, Italy.
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Tran P, Zhou S, Wang L, Finegold M, Mascarenhas L, Alexopolous S, Genyk Y, Kerkar N. De novo hepatocellular carcinoma post-multivisceral transplantation in a child. Pediatr Transplant 2017; 21. [PMID: 29024228 DOI: 10.1111/petr.12991] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/09/2017] [Indexed: 12/23/2022]
Abstract
De novo hepatocellular carcinoma (HCC) post-transplantation in patients without viral hepatitis is extremely rare, with only three reported adult cases in the English literature. Here, we present a case of de novo HCC that developed in a 7-year-old female, who at 8 months of age received a liver, small bowel, spleen, and pancreas transplantation 6.5 years ago for gastroschisis and total parenteral nutrition (TPN)-related cirrhosis. The post-transplant course was complicated by Epstein-Barr virus (EBV) infection, post-transplant lymphoproliferative disease, and subsequent development of multifocal EBV-associated post-transplant smooth muscle tumors (EBV-PTSMT) in the small bowel 1 year and 10 months after transplantation, respectively. This was managed by reducing immunosuppression with rituximab and EBV-specific cytotoxic T-cell therapy. She was noted to have a new lesion in her transplanted liver graft 6.5 years post-transplantation that was diagnosed as HCC. The HCC was resected, and the patient remained clinically stable for 7 months. At that time, recurrence of the HCC was discovered on MRI. She passed away 6 months after. To the best of our knowledge, this is the first reported occurrence of de novo HCC post-transplantation in the pediatric population that is unrelated to viral hepatitis in either recipient or donor.
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Affiliation(s)
- P Tran
- Department of Pediatrics, Keck School of Medicine, Division of Gastroenterology, Hepatology & Nutrition, University of Southern California, Los Angeles, CA, USA
| | - S Zhou
- Department of Pathology and Laboratory Medicine, Children's Hospital of Los Angeles, Los Angeles, CA, USA
| | - L Wang
- Department of Pathology and Laboratory Medicine, Children's Hospital of Los Angeles, Los Angeles, CA, USA
| | - M Finegold
- Department of Pathology, Texas Children's Hospital, Houston, TX, USA
| | - L Mascarenhas
- Department of Hematology/Oncology, Children's Hospital of Los Angeles, Los Angeles, CA, USA
| | - S Alexopolous
- Department of Pediatrics, Keck School of Medicine, Division of Gastroenterology, Hepatology & Nutrition, University of Southern California, Los Angeles, CA, USA.,Division of Abdominal Transplantation, Department of Surgery, Children's Hospital of Los Angeles, Los Angeles CA, USA
| | - Y Genyk
- Department of Pediatrics, Keck School of Medicine, Division of Gastroenterology, Hepatology & Nutrition, University of Southern California, Los Angeles, CA, USA.,Division of Abdominal Transplantation, Department of Surgery, Children's Hospital of Los Angeles, Los Angeles CA, USA
| | - N Kerkar
- Department of Pediatrics, Keck School of Medicine, Division of Gastroenterology, Hepatology & Nutrition, University of Southern California, Los Angeles, CA, USA.,Division of Gastroenterology, Hepatology and Nutrition, Golisano Children's Hospital, University of Rochester Medical Center, Rochester, NY, USA
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