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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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Jagdish RK, Chappity P, Lata S. Dental and ENT Evaluation Before Liver Transplantation. J Clin Exp Hepatol 2024; 14:101431. [PMID: 38745755 PMCID: PMC11090062 DOI: 10.1016/j.jceh.2024.101431] [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: 07/16/2023] [Accepted: 04/14/2024] [Indexed: 05/16/2024] Open
Abstract
The assessment of dental and ear, nose and throat (ENT) conditions holds significant importance in the pre-transplantation evaluation for individuals undergoing liver transplantation. This evaluation aims to address concerns related to dental and ENT issues both before and after liver transplantation. These concerns include the risk of sepsis, the impact of post-transplantation immunosuppression, the detection of existing malignancies, including oral potentially malignant disorders (OPMDs), and identifying any contraindications to the transplantation procedure. However, it is worth noting that there exists a notable absence of clear guidelines and protocols in the existing literature regarding this practice. Moreover, recent studies have presented conflicting results, and concerns have arisen regarding the cost-effectiveness of these evaluations. It is crucial to perform these investigations judiciously to avoid unnecessary testing burdens and delays in placing patients on waiting lists, particularly when considering live donor liver transplantation (LDLT) evaluations. A comprehensive examination of the oral and ENT regions, in conjunction with relevant laboratory tests, can play a pivotal role in identifying and managing oral and ENT diseases before the liver transplantation procedure. Timely recognition and treatment of potential issues are essential for minimizing perioperative morbidity and mortality. There is an evident need for prospective trials and studies to further explore and establish guidelines in the critical area of dental and ENT evaluation in liver transplantation recipients. Such research efforts would contribute significantly to enhancing our understanding and management of oral and ENT conditions in the pre-transplantation setting, ultimately improving patient care and outcomes.
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Affiliation(s)
- Rakesh K. Jagdish
- Hepatology, Gastroenterology and Liver Transplant Medicine, Pan Metro Group of Hospitals, Delhi and NCR, India
| | - Preetam Chappity
- Department of Otorhinolaryngology and Head & Neck Surgery, A.I.I.M.S, Bhubaneswar, Odisha, 751019, India
| | - S. Lata
- Department of Conservative Dentistry and Endodontics, Kalinga Institute of Dental Sciences, Bhubaneswar, Odisha, 751019, India
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Zhao L, Wang Y, Guo Z. Successful treatment of gastric cancer 10 years after heart transplantation: A case report. Medicine (Baltimore) 2024; 103:e37841. [PMID: 38640302 PMCID: PMC11029957 DOI: 10.1097/md.0000000000037841] [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: 12/27/2023] [Accepted: 03/19/2024] [Indexed: 04/21/2024] Open
Abstract
BACKGROUND While survival rates among cardiac allograft recipients have improved, there has been a rise in post-transplant malignancies, with gastric cancer being less commonly reported. This study presented a successful treatment of gastric cancer in an individual 10 years after undergoing a heart transplant. CASE PRESENTATION A 66-year-old Chinese man presented to the gastrointestinal clinic with a complaint of diagnosis of gastric cancer for 4 months and treated with neoadjuvant therapy for 1 month. He has undergone orthotopic heart transplantation 10 years earlier due to a myocardial infarction. Physical examination and laboratory tests did not reveal any significant abnormalities. Abdominal contrast-enhanced computed tomography (CT) imaging indicated a gastric mass near the greater curvature, with gastroscopy suggesting a carcinoma at the esophagogastric junction, Siewert III. An echocardiogram indicated left atrial enlargement with mild mitral and tricuspid regurgitation. The diagnosis suggested that his gastric cancer at the esophagogastric junction was a consequence of long-term immunosuppressive therapy. A multidisciplinary team (MDT) consultation recommended a proximal radical gastrectomy. Postoperatively, the patient received 4 cycles of adjuvant chemotherapy with XELOX combined with Herceptin, initiated a month after surgery. During the 1-year follow-up, the patient showed commendable recovery, with no signs of tumor recurrence or metastasis. CONCLUSION This case underscores the potential risk of malignancy from immunosuppressive agents in transplant recipients. The successful management of this complex scenario underscores the indispensable role of an MDT approach in treating such unique and challenging cases.
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Affiliation(s)
- Lin Zhao
- Department of Anesthesiology, Peking University, Shougang Hospital, Shijingshan District, Beijing, China
| | - Ye Wang
- Department of Anesthesiology, Peking University, Shougang Hospital, Shijingshan District, Beijing, China
| | - Zhenggang Guo
- Department of Anesthesiology, Peking University, Shougang Hospital, Shijingshan District, Beijing, China
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Eurich D, Schlickeiser S, Ossami Saidy RR, Uluk D, Rossner F, Postel M, Schoening W, Oellinger R, Lurje G, Pratschke J, Reinke P, Gruen N. How to Estimate the Probability of Tolerance Long-Term in Liver Transplant Recipients. J Clin Med 2023; 12:6546. [PMID: 37892685 PMCID: PMC10607917 DOI: 10.3390/jcm12206546] [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: 09/03/2023] [Revised: 09/29/2023] [Accepted: 10/11/2023] [Indexed: 10/29/2023] Open
Abstract
BACKGROUND Operational tolerance as the ability to accept the liver transplant without pharmacological immunosuppression is a common phenomenon in the long-term course. However, it is currently underutilized due to a lack of simple diagnostic support and fear of rejection despite its recognized benefits. In the present work, we present a simple score based on clinical parameters to estimate the probability of tolerance. PATIENTS AND METHODS In order to estimate the probability of tolerance, clinical parameters from 82 patients after LT who underwent weaning from the IS for various reasons at our transplant center were extracted from a prospectively organized database and analyzed retrospectively. Univariate testing as well as multivariable logistic regression analysis were performed to assess the association of clinical variables with tolerance in the real-world setting. RESULTS The most important factors associated with tolerance after multivariable logistic regression were IS monotherapy, male sex, history of hepatocellular carcinoma pretransplant, time since LT, and lack of rejection. These five predictors were retained in an approximate model that could be presented as a simple scoring system to estimate the clinical probability of tolerance or IS dispensability with good predictive performance (AUC = 0.89). CONCLUSION In parallel with the existence of a tremendous need for further research on tolerance mechanisms, the presented score, after validation in a larger collective preferably in a multicenter setting, could be easily and safely applied in the real world and already now address all three levels of prevention in LT patients over the long-term course.
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Affiliation(s)
- Dennis Eurich
- Department of Surgery, Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany; (R.R.O.S.); (D.U.); (M.P.); (W.S.); (R.O.); (G.L.); (J.P.)
| | - Stephan Schlickeiser
- Berlin Institute of Health (BIH) Center for Regenerative Therapies (BCRT), Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany; (S.S.); (P.R.)
| | - Ramin Raul Ossami Saidy
- Department of Surgery, Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany; (R.R.O.S.); (D.U.); (M.P.); (W.S.); (R.O.); (G.L.); (J.P.)
| | - Deniz Uluk
- Department of Surgery, Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany; (R.R.O.S.); (D.U.); (M.P.); (W.S.); (R.O.); (G.L.); (J.P.)
| | - Florian Rossner
- Department of Pathology, Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany;
- Max Delbrueck Center for Molecular Medicine, Helmholtz Association, 13125 Berlin, Germany
| | - Maximilian Postel
- Department of Surgery, Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany; (R.R.O.S.); (D.U.); (M.P.); (W.S.); (R.O.); (G.L.); (J.P.)
| | - Wenzel Schoening
- Department of Surgery, Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany; (R.R.O.S.); (D.U.); (M.P.); (W.S.); (R.O.); (G.L.); (J.P.)
| | - Robert Oellinger
- Department of Surgery, Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany; (R.R.O.S.); (D.U.); (M.P.); (W.S.); (R.O.); (G.L.); (J.P.)
| | - Georg Lurje
- Department of Surgery, Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany; (R.R.O.S.); (D.U.); (M.P.); (W.S.); (R.O.); (G.L.); (J.P.)
| | - Johann Pratschke
- Department of Surgery, Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany; (R.R.O.S.); (D.U.); (M.P.); (W.S.); (R.O.); (G.L.); (J.P.)
| | - Petra Reinke
- Berlin Institute of Health (BIH) Center for Regenerative Therapies (BCRT), Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany; (S.S.); (P.R.)
- Berlin Center for Advanced Therapies (BeCAT), Berlin Institute of Health (BIH) Center for Regenerative Therapies (BCRT), Charité—Universitaetsmedizin Berlin, 13353 Berlin, Germany;
| | - Natalie Gruen
- Berlin Center for Advanced Therapies (BeCAT), Berlin Institute of Health (BIH) Center for Regenerative Therapies (BCRT), Charité—Universitaetsmedizin Berlin, 13353 Berlin, Germany;
- Department of Nephrology and Internal Intensive Care Medicine, Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany
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Muraki P, Lee C, Patel N, Arevalo A, Ohtake S, Mendhiratta N, Chamie K, Agopian V, Benharash P, Shuch B. Perioperative Nephrectomy Outcomes for Patients with Liver Disease: Implications for Liver Transplant Candidates. Urology 2023; 173:127-133. [PMID: 36403677 DOI: 10.1016/j.urology.2022.10.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 09/26/2022] [Accepted: 10/23/2022] [Indexed: 11/19/2022]
Abstract
OBJECTIVE To improve the management of cirrhotic patients diagnosed with new renal masses, we used a nationally representative cohort to assess the perioperative outcomes of nephrectomy in the setting of liver disease. The incidences of liver disease and renal masses are both rising in the US. Delaying liver transplantation to address other health concerns may have life changing consequences in these patients, thus these results help to guide treatment decisions at this critical junction in care. METHODS A retrospective study of the 2016-2019 Nationwide Readmissions Database was performed in adults undergoing nephrectomy for non-emergent indications. Outcomes were compared between 3 cohorts: no chronic liver disease (no CLD), chronic liver disease (CLD), and decompensated cirrhosis (DC). Mixed regression models were used to evaluate the association between CLD and DC with outcomes of interest including morbidity, mortality, readmission rates, non-home discharges, length of stay, and costs. RESULTS A total of 183,362 patients were evaluated. The mortality rate in the DC cohort (7%) was higher than with CLD (0.4%) and no CLD (0.3%), (P <.001). DC was associated with higher mortality (OR 8.29, 95% CI 4.07 - 16.88), postoperative bleeding requiring transfusion (OR 5.55, 95% CI 3.72 - 8.26), non-home discharge (OR 5.12, 95% CI 3.16 - 8.30) and readmission (OR 1.79, 95% CI 1.09 - 2.94) compared to no CLD. The DC cohort had the greatest length of stay and costs. CONCLUSION Patients undergoing nephrectomy with DC have increased morbidity, mortality, readmission rates, non-home discharges, LOS and costs. Alternative management strategies may be considered in these patients.
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Affiliation(s)
- Peter Muraki
- Institute of Urologic Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Cory Lee
- Cardiovascular Outcomes Research Laboratories, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Neal Patel
- Institute of Urologic Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | | | - Shinji Ohtake
- Institute of Urologic Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Neil Mendhiratta
- Institute of Urologic Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Karim Chamie
- Institute of Urologic Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Vatche Agopian
- Dumont-UCLA Liver Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Peyman Benharash
- Cardiovascular Outcomes Research Laboratories, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Brian Shuch
- Institute of Urologic Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA.
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Martinez-Castillo M, Altamirano-Mendoza I, Zielinski R, Priebe W, Piña-Barba C, Gutierrez-Reyes G. Collagen matrix scaffolds: Future perspectives for the management of chronic liver diseases. World J Clin Cases 2023; 11:1224-1235. [PMID: 36926129 PMCID: PMC10013111 DOI: 10.12998/wjcc.v11.i6.1224] [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: 10/10/2022] [Revised: 11/21/2022] [Accepted: 02/02/2023] [Indexed: 02/23/2023] Open
Abstract
Approximately 1.5 billion chronic liver disease (CLD) cases have been estimated worldwide, encompassing a wide range of liver damage severities. Moreover, liver disease causes approximately 1.75 million deaths per year. CLD is typically characterized by the silent and progressive deterioration of liver parenchyma due to an incessant inflammatory process, cell death, over deposition of extracellular matrix proteins, and dysregulated regeneration. Overall, these processes impair the correct function of this vital organ. Cirrhosis and liver cancer are the main complications of CLD, which accounts for 3.5% of all deaths worldwide. Liver transplantation is the optimal therapeutic option for advanced liver damage. The liver is one of the most common organs transplanted; however, only 10% of liver transplants are successful. In this context, regenerative medicine has made significant progress in the design of biomaterials, such as collagen matrix scaffolds, to address the limitations of organ transplantation (e.g., low donation rates and biocompatibility). Thus, it remains crucial to continue with experimental and clinical studies to validate the use of collagen matrix scaffolds in liver disease.
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Affiliation(s)
- Moises Martinez-Castillo
- Liver, Pancreas and Motility Laboratory, Unit of Experimental Medicine, School of Medicine, Universidad Nacional Autonoma de Mexico, Mexico City 06726, Mexico City, Mexico
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, United States
| | - Itzel Altamirano-Mendoza
- Liver, Pancreas and Motility Laboratory, Unit of Experimental Medicine, School of Medicine, Universidad Nacional Autonoma de Mexico, Mexico City 06726, Mexico City, Mexico
| | - Rafal Zielinski
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, United States
| | - Waldemar Priebe
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, United States
| | - Cristina Piña-Barba
- Materials Research Institute, Universidad Nacional Autónoma de México, Mexico City 06726, Mexico City, Mexico
| | - Gabriela Gutierrez-Reyes
- Liver, Pancreas and Motility Laboratory, Unit of Experimental Medicine, School of Medicine, Universidad Nacional Autonoma de Mexico, Mexico City 06726, Mexico City, Mexico
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Hart A, Pfeiffer RM, Morawski BM, Lynch CF, Zeng Y, Pawlish K, Hurley D, Yu KJ, Engels EA. Mortality among solid organ transplant recipients with a pretransplant cancer diagnosis. Am J Transplant 2023; 23:257-264. [PMID: 36804133 PMCID: PMC9978936 DOI: 10.1016/j.ajt.2022.11.006] [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: 07/01/2022] [Revised: 10/10/2022] [Accepted: 11/08/2022] [Indexed: 01/15/2023]
Abstract
Little is known about the outcomes among solid organ transplant recipients with a pretransplant cancer diagnosis. We used linked data from the Scientific Registry of Transplant Recipients with 33 US cancer registries. Cox proportional hazards models assessed associations of pretransplant cancer with overall mortality, cancer-specific mortality, and development of a new posttransplant cancer. Among 311 677 recipients, the presence of a single pretransplant cancer was associated with increased overall mortality (adjusted hazard ratio [aHR], 1.19; 95% CI, 1.15-1.23) and cancer-specific mortality (aHR, 1.93; 95% CI, 1.76-2.12); results for 2+ pretransplant cancers were similar. Cancer-specific mortality was not significantly increased for uterine, prostate, or thyroid cancers (aHRs were 0.83, 1.22, and 1.54, respectively) but strongly elevated for lung cancer and myeloma (aHRs were 3.72 and 4.42, respectively). A pretransplant cancer diagnosis was also associated with increased risk of developing posttransplant cancer (aHR, 1.32; 95% CI, 1.23-1.40). Among 306 recipients whose cancer death was confirmed by cancer registry data, 158 deaths (51.6%) were from a de novo posttransplant cancer and 105 (34.3%) from the pretransplant cancer. Pretransplant cancer diagnoses are associated with increased mortality after transplantation, but some deaths are related to posttransplant cancers and other causes. Improved candidate selection and cancer screening and prevention may reduce mortality in this population.
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Affiliation(s)
- Allyson Hart
- Scientific Registry of Transplant Recipients, Minneapolis, Minnesota, USA.
| | - Ruth M Pfeiffer
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Bozena M Morawski
- Cancer Data Registry of Idaho, Idaho Hospital Association, Boise, Idaho, USA
| | - Charles F Lynch
- University of Iowa Department of Epidemiology, Iowa City, Iowa, USA
| | - Yun Zeng
- University of North Dakota Department of Pathology, North Dakota Statewide Cancer Registry, Grand Forks, North Dakota, USA
| | - Karen Pawlish
- New Jersey State Cancer Registry, New Jersey Department of Health, Trenton, New Jersey, USA
| | - Deborah Hurley
- South Carolina Central Cancer Registry Bureau of Chronic Disease & Injury Prevention, Columbia, South Carolina, USA
| | - Kelly J Yu
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Eric A Engels
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
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Pérez-Escobar J, Jimenez JV, Rodríguez-Aguilar EF, Servín-Rojas M, Ruiz-Manriquez J, Safar-Boueri L, Carrillo-Maravilla E, Navasa M, García-Juárez I. Immunotolerance in liver transplantation: a primer for the clinician. Ann Hepatol 2023; 28:100760. [PMID: 36179797 DOI: 10.1016/j.aohep.2022.100760] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 09/08/2022] [Indexed: 02/04/2023]
Abstract
The use of immunosuppressive medications for solid organ transplantation is associated with cardiovascular, metabolic, and oncologic complications. On the other hand, the development of graft rejection is associated with increased mortality and graft dysfunction. Liver transplant recipients can withdraw from immunosuppression without developing graft injury while preserving an adequate antimicrobial response - a characteristic known as immunotolerance. Immunotolerance can be spontaneously or pharmacologically achieved. Contrary to the classic dogma, clinical studies have elucidated low rates of true spontaneous immunotolerance (no serologic or histological markers of immune injury) among liver transplant recipients. However, clinical, serologic, and tissue biomarkers can aid in selecting patients in whom immunosuppression can be safely withdrawn. For those who failed an immunosuppression withdrawal trial or are at high risk of rejection, pharmacological interventions for immunotolerance induction are under development. In this review, we provide an overview of the mechanisms of immunotolerance, the clinical studies investigating predictors and biomarkers of spontaneous immunotolerance, as well as the potential pharmacological interventions for inducing it.
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Affiliation(s)
- Juanita Pérez-Escobar
- Department of Hepatology and Liver Transplant, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Jose Victor Jimenez
- Department of Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Erika Faride Rodríguez-Aguilar
- Department of Hepatology and Liver Transplant, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Maximiliano Servín-Rojas
- Department of Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Jesus Ruiz-Manriquez
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Luisa Safar-Boueri
- Comprehensive Transplant Center, Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
| | - Eduardo Carrillo-Maravilla
- Department of Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Miquel Navasa
- Liver Transplant Unit, Hepatology Service, Hospital Clínic de Barcelona, IDIBAPS, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - Ignacio García-Juárez
- Department of Hepatology and Liver Transplant, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
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10
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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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Chacko SR, Matta A, Bhat R, Minimo C, Benzaquen S, Gupta E. A 62-Year-Old Immunocompromised Man With Halo Sign on Chest Imaging. Chest 2022; 162:e177-e181. [DOI: 10.1016/j.chest.2022.04.156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 03/27/2022] [Accepted: 04/23/2022] [Indexed: 11/05/2022] Open
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12
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Pesthy S, Wegener E, Ossami Saidy RR, Timmermann L, Uluk D, Aydin M, Dziodzio T, Schoening W, Lurje G, Öllinger R, Frost N, Fehrenbach U, Rückert JC, Neudecker J, Pratschke J, Eurich D. Reducing Immunosuppression in Patients with De Novo Lung Carcinoma after Liver Transplantation Could Significantly Prolong Survival. Cancers (Basel) 2022; 14:cancers14112748. [PMID: 35681728 PMCID: PMC9179580 DOI: 10.3390/cancers14112748] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 05/26/2022] [Accepted: 05/27/2022] [Indexed: 02/01/2023] Open
Abstract
(1) Background: Liver transplantation (LT) is an established treatment for selected patients with end-stage liver disease resulting in a subsequent need for long-term immunosuppressive therapy. With cumulative exposure to immunosuppression (IS), the risk for the development of de novo lung carcinoma increases. Due to limited therapy options and prognosis after diagnosis of lung cancer, the question of the mode and extent of IS in this particular situation is raised. (2) Methods: All patients diagnosed with de novo lung cancer in the follow-up after LT were identified from the institution's register of liver allograft recipients (Charité-Universitätsmedizin Berlin, Germany) transplanted between 1988 and 2021. Survival analysis was performed based on the IS therapy following diagnosis of lung cancer and the oncological treatment approach. (3) Results: Among 3207 adult LTs performed in 2644 patients at our institution, 62 patients (2.3%) developed de novo lung carcinoma following LT. Lung cancer was diagnosed at a median interval of 9.7 years after LT (range 0.7-27.0 years). Median survival after diagnosis of lung carcinoma was 13.2 months (range 0-196 months). Surgical approach with curative intent significantly prolonged survival rates compared to palliative treatment (median 67.4 months vs. 6.4 months). Reduction of IS facilitated a significant improvement in survival (median 38.6 months vs. 6.7 months). In six patients (9.7%) complete IS weaning was achieved with unimpaired liver allograft function. (4) Conclusion: Reduction of IS therapy after the diagnosis of de novo lung cancer in LT patients is associated with prolonged survival. The risk of acute rejection does not appear to be increased with restrictive IS management. Therefore, strict reduction of IS should be an early intervention following diagnosis. In addition, surgical resection should be attempted, if technically feasible and oncologically meaningful.
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Affiliation(s)
- Sina Pesthy
- Department of Surgery, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (E.W.); (R.R.O.S.); (L.T.); (D.U.); (M.A.); (T.D.); (W.S.); (G.L.); (R.Ö.); (J.-C.R.); (J.N.); (J.P.); (D.E.)
- Correspondence: ; Tel.: +49-30-450-652316
| | - Elisa Wegener
- Department of Surgery, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (E.W.); (R.R.O.S.); (L.T.); (D.U.); (M.A.); (T.D.); (W.S.); (G.L.); (R.Ö.); (J.-C.R.); (J.N.); (J.P.); (D.E.)
| | - Ramin Raul Ossami Saidy
- Department of Surgery, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (E.W.); (R.R.O.S.); (L.T.); (D.U.); (M.A.); (T.D.); (W.S.); (G.L.); (R.Ö.); (J.-C.R.); (J.N.); (J.P.); (D.E.)
| | - Lea Timmermann
- Department of Surgery, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (E.W.); (R.R.O.S.); (L.T.); (D.U.); (M.A.); (T.D.); (W.S.); (G.L.); (R.Ö.); (J.-C.R.); (J.N.); (J.P.); (D.E.)
| | - Deniz Uluk
- Department of Surgery, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (E.W.); (R.R.O.S.); (L.T.); (D.U.); (M.A.); (T.D.); (W.S.); (G.L.); (R.Ö.); (J.-C.R.); (J.N.); (J.P.); (D.E.)
| | - Mustafa Aydin
- Department of Surgery, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (E.W.); (R.R.O.S.); (L.T.); (D.U.); (M.A.); (T.D.); (W.S.); (G.L.); (R.Ö.); (J.-C.R.); (J.N.); (J.P.); (D.E.)
| | - Tomasz Dziodzio
- Department of Surgery, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (E.W.); (R.R.O.S.); (L.T.); (D.U.); (M.A.); (T.D.); (W.S.); (G.L.); (R.Ö.); (J.-C.R.); (J.N.); (J.P.); (D.E.)
- BIH Charité Clinician Scientist Program, Berlin Institute of Health at Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany
| | - Wenzel Schoening
- Department of Surgery, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (E.W.); (R.R.O.S.); (L.T.); (D.U.); (M.A.); (T.D.); (W.S.); (G.L.); (R.Ö.); (J.-C.R.); (J.N.); (J.P.); (D.E.)
| | - Georg Lurje
- Department of Surgery, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (E.W.); (R.R.O.S.); (L.T.); (D.U.); (M.A.); (T.D.); (W.S.); (G.L.); (R.Ö.); (J.-C.R.); (J.N.); (J.P.); (D.E.)
| | - Robert Öllinger
- Department of Surgery, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (E.W.); (R.R.O.S.); (L.T.); (D.U.); (M.A.); (T.D.); (W.S.); (G.L.); (R.Ö.); (J.-C.R.); (J.N.); (J.P.); (D.E.)
| | - Nikolaj Frost
- Department of Infectious Diseases and Pulmonary Medicine, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany;
| | - Uli Fehrenbach
- Department of Radiology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany;
| | - Jens-Carsten Rückert
- Department of Surgery, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (E.W.); (R.R.O.S.); (L.T.); (D.U.); (M.A.); (T.D.); (W.S.); (G.L.); (R.Ö.); (J.-C.R.); (J.N.); (J.P.); (D.E.)
| | - Jens Neudecker
- Department of Surgery, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (E.W.); (R.R.O.S.); (L.T.); (D.U.); (M.A.); (T.D.); (W.S.); (G.L.); (R.Ö.); (J.-C.R.); (J.N.); (J.P.); (D.E.)
| | - Johann Pratschke
- Department of Surgery, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (E.W.); (R.R.O.S.); (L.T.); (D.U.); (M.A.); (T.D.); (W.S.); (G.L.); (R.Ö.); (J.-C.R.); (J.N.); (J.P.); (D.E.)
| | - Dennis Eurich
- Department of Surgery, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (E.W.); (R.R.O.S.); (L.T.); (D.U.); (M.A.); (T.D.); (W.S.); (G.L.); (R.Ö.); (J.-C.R.); (J.N.); (J.P.); (D.E.)
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13
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Clinical characteristics and survival analysis of liver transplantation in patients with alcoholic liver disease: A single-center retrospective study. Transpl Immunol 2022; 72:101569. [DOI: 10.1016/j.trim.2022.101569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 02/28/2022] [Accepted: 02/28/2022] [Indexed: 11/21/2022]
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Koseki Y, Kamimura K, Tanaka Y, Ohkoshi-Yamada M, Zhou Q, Matsumoto Y, Mizusawa T, Sato H, Sakamaki A, Umezu H, Yokoyama J, Terai S. Rapid progression of colonic mucinous adenocarcinoma with immunosuppressive condition: A case report and review of literature. World J Clin Cases 2021; 9:9182-9191. [PMID: 34786403 PMCID: PMC8567511 DOI: 10.12998/wjcc.v9.i30.9182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 06/29/2021] [Accepted: 09/08/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Colorectal mucinous adenocarcinoma is a rare subtype of colorectal cancer and is characterized by an abundance of mucin in the tumor. In addition, the colorectal mucinous adenocarcinoma often demonstrates poor differentiation in the histology of tumor cells and poor prognosis compared with those with adenocarcinoma. Here, we present the case of a young woman with colonic mucinous adenocarcinoma showing significantly rapid progression within four months of immunosuppressant therapy for Henoch-Schönlein purpura. CASE SUMMARY Here we report a rare case of ascending colon mucinous adenocarcinoma with lymph node and liver metastases which developed and progressed rapidly within four months during the treatment of Henoch-Schönlein purpura using corticosteroids. The systemic screening examinations showed no tumors before the immunosuppressant therapy. Fortunately, the patient was successfully treated with chemotherapy. CONCLUSION While no direct evidence that the immunosuppressants accelerated the tumor development, the case presenta tion and review of the literature demonstrated that surveillance for malignancies before and during treatment with immunosuppressive agents is essential.
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Affiliation(s)
- Youhei Koseki
- Division of Gastroenterology and Hepatology, Niigata University, Niigata 9518510, Japan
| | - Kenya Kamimura
- Division of Gastroenterology and Hepatology, Niigata University, Niigata 9518510, Japan
- Department of General Medicine, Niigata University, Niigata 9518510, Japan
| | - Yuto Tanaka
- Division of Gastroenterology and Hepatology, Niigata University, Niigata 9518510, Japan
| | - Marina Ohkoshi-Yamada
- Division of Gastroenterology and Hepatology, Niigata University, Niigata 9518510, Japan
| | - Qiliang Zhou
- Department of Medical Oncology, Niigata University, Niigata 9518510, Japan
| | | | - Takeshi Mizusawa
- Division of Gastroenterology and Hepatology, Niigata University, Niigata 9518510, Japan
| | - Hiroki Sato
- Division of Gastroenterology and Hepatology, Niigata University, Niigata 9518510, Japan
| | - Akira Sakamaki
- Division of Gastroenterology and Hepatology, Niigata University, Niigata 9518510, Japan
| | - Hajime Umezu
- Division of Pathology, Niigata University, Niigata 9518510, Japan
| | - Junji Yokoyama
- Division of Gastroenterology and Hepatology, Niigata University, Niigata 9518510, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Niigata University, Niigata 9518510, Japan
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15
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Patel JA, Daoud D, Jain A. Review of Standardized Incidence Ratios (SIR) of non-lymphoid de novo malignancies after liver transplantation: Structured analysis of global differences. Transplant Rev (Orlando) 2021; 36:100670. [PMID: 34688986 DOI: 10.1016/j.trre.2021.100670] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 10/13/2021] [Accepted: 10/14/2021] [Indexed: 12/16/2022]
Abstract
INTRODUCTION De Novo malignancy after liver transplantation (LTx) is the second most common cause of death in adult LTx recipients. The current report identifies differences in Standardized Incidence Ratios (SIR) for various non-lymphoid de novo malignancies by comparing and analyzing post LTx SIR for non-lymphoid de novo malignancies. MATERIAL AND METHODS A thorough search of PubMed and Web of Science databases was conducted; 25 publications describing de novo malignancies post-LTx with SIR were identified. RESULTS Overall SIR varied from 1.4 to 11.6 (median 2.4). Oropharyngeal/larynx (OPL), lung, colo-rectal, and kidney malignancies were more prevalent with higher SIR (median = 4.4, 1.9, 2.67, 2.5, respectively). Breast and prostate malignancies were also more prevalent with lower SIR (median = 0.9, 1.0, respectively). Pancreatic, central nervous system (CNS), melanoma, rare cancers and Kaposi's sarcoma were less prevalent (except in Italy and Sweden) but had much higher SIR (median = 2.6, 2.4, 2.02, 22.5 and 53.6, respectively). The overall higher SIR values are related to the age of the recipient, length of follow-up, the grouping of different organ systems, inclusion or exclusion of epidermal non-malacotic skin cancers, lymphoid malignancy, and occurrence of rare malignancies including Kaposi's sarcoma. CONCLUSION OPL, lung, gastrointestinal, kidney, and bladder malignancies were more prevalent with higher SIR. Breast and prostate cancers were more prevalent with lower SIR. Pancreatic, CNS, melanoma, rare cancers and Kaposi's sarcoma were less prevalent with higher SIR. Age of the recipients, length of follow-up, and rare cancer types influence overall SIR values with some global differences.
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Affiliation(s)
- Jay A Patel
- Department of General Surgery, The Pennsylvania State University, College of Medicine, Hershey, PA, USA
| | - Deborah Daoud
- Division of Transplant Surgery, The Pennsylvania State University, College of Medicine, Hershey, PA, USA
| | - Ashokkumar Jain
- Department of General Surgery, The Pennsylvania State University, College of Medicine, Hershey, PA, USA; Division of Transplant Surgery, The Pennsylvania State University, College of Medicine, Hershey, PA, USA.
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16
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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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Grassi G, Lenci I, Signorello A, Milana M, Baiocchi L. Gastrointestinal endoscopy in cirrhotic patient: Issues on the table. World J Gastrointest Endosc 2021; 13:210-220. [PMID: 34326942 PMCID: PMC8311468 DOI: 10.4253/wjge.v13.i7.210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 06/22/2021] [Accepted: 06/28/2021] [Indexed: 02/06/2023] Open
Abstract
Patients with liver cirrhosis are fragile and present specific clinical hallmarks. When undergoing to gastrointestinal (GI) endoscopy, these subjects require an individual pre evaluation, taking into account: Level of haemostasis impairment, the individual risk of infection, the impact of sedation on hepatic encephalopathy and other factors. The overall assessment of liver function, employing common scoring systems, should be also assessed in the preprocedural phase. Beside some common general problems, regarding GI endoscopy in cirrhotic subjects, also specific issues are present for some frequent indications or procedures. For instance, despite an increased incidence of adenomas in cirrhosis, colon cancer screening remains suboptimal in subjects with this disease. Several studies in fact demonstrated liver cirrhosis as a negative factor for an adequate colon cleansing before colonoscopy. On the other hand, also the routine assessment of gastroesophageal varices during upper GI endoscopy presents some concern, since important inter-observer variability or incomplete description of endoscopic findings has been reported in some studies. In this review we discussed in details the most relevant issues that may be considered while performing general GI endoscopic practice, in patient with cirrhosis. For most of these issues there are no guidelines or clear indications. Moreover until now, few studies focused on these aspects. We believe that targeting these issues with corrective measures may be helpful to develop a tailored endoscopic approach for cirrhosis, in the future.
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Affiliation(s)
- Giuseppe Grassi
- Hepatology Unit, University of Tor Vergata, Rome 00100, Italy
| | - Ilaria Lenci
- Hepatology Unit, University of Tor Vergata, Rome 00100, Italy
| | | | - Martina Milana
- Hepatology Unit, University of Tor Vergata, Rome 00100, Italy
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18
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Low ESL, Gow PJ, Testro A, Sinclair M. Low participation in preventative health measures in a cohort of liver transplant recipients: A cross-sectional analysis. Clin Transplant 2021; 35:e14257. [PMID: 33605483 DOI: 10.1111/ctr.14257] [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: 08/23/2020] [Revised: 01/20/2021] [Accepted: 02/13/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND Despite high rates of infection and malignancy post-solid organ transplant, there are little data on patient participation in preventative health care. METHODS We conducted a cross-sectional survey of post-liver transplant patients to evaluate insight into transplant-associated infective and neoplastic risks, and receipt of vaccination and cancer surveillance in accordance with Australian and local institution-specific guidelines. Descriptive analyses were used to assess characteristics potentially influencing adherence. RESULTS Of 219 patients surveyed, adherence to bowel cancer surveillance was significantly reduced in those distant from transplantation compared with those recently transplanted (95.8% if transplanted ≤ 5 years ago vs. 68.3% if transplanted > 5 years ago, P < .001). Skin cancer surveillance participation with annual physician-directed examination was low (42.9%), particularly in younger patients (29.5% in < 50yo vs. 48.1% in ≥ 50yo, P = .01), who were also less adherent to vaccination recommendations (72.1% in < 50yo vs. 87.3% in ≥ 50yo, P = .008). CONCLUSIONS This is the first analysis of preventative healthcare participation in a cohort of Australian liver transplant recipients, revealing concerning adherence to bowel and skin cancer surveillance recommendations. Major interventions to avoid preventable disease in this high-risk cohort are warranted.
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Affiliation(s)
| | - Paul J Gow
- Austin Health Liver Transplant Unit, Heidelberg, Vic, Australia
- Department of Medicine, The University of Melbourne, Parkville, Vic, Australia
| | - Adam Testro
- Austin Health Liver Transplant Unit, Heidelberg, Vic, Australia
- Department of Medicine, The University of Melbourne, Parkville, Vic, Australia
| | - Marie Sinclair
- Austin Health Liver Transplant Unit, Heidelberg, Vic, Australia
- Department of Medicine, The University of Melbourne, Parkville, Vic, Australia
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19
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Wahab MA, Abdel-Khalek EE, Elshoubary M, Yassen AM, Salah T, Sultan AM, Fathy O, Elmorshedi M, Shiha U, Elsadany M, Adly R, Samy M, Shehta A. Predictive Factors of De Novo Malignancies After Living-Donor Liver Transplantation: A Single-Center Experience. Transplant Proc 2021; 53:636-644. [PMID: 33549346 DOI: 10.1016/j.transproceed.2021.01.033] [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: 06/03/2020] [Revised: 11/14/2020] [Accepted: 01/08/2021] [Indexed: 11/17/2022]
Abstract
BACKGROUND De novo malignancies are a major reason of long-term mortalities after liver transplantation. However, they usually receive minimal attention from most health care specialists. The current study aims to evaluate our experience of de novo malignancies after living-donor liver transplantation (LDLT). METHODS We reviewed the data of patients who underwent LDLT at our center during the period between May 2004 and December 2018. RESULTS During the study period, 640 patients underwent LDLT. After a mean follow-up period of 41.2 ± 25.8 months, 15 patients (2.3%) with de novo malignancies were diagnosed. The most common de novo malignancies were cutaneous cancers (40%), post-transplantation lymphoproliferative disorders (13.3%), colon cancers (13.3%), and breast cancers (13.3%). Acute cellular rejection (ACR) episodes occurred in 10 patients (66.7%). Mild ACR occurred in 8 patients (53.3%), and moderate ACR occurred in 2 patients (13.3%). All patients were managed with aggressive cancer treatment. The mean survival after therapy was 40.8 ± 26.4 months. The mean overall survival after LDLT was 83.9 ± 52.9 months. Twelve patients (80%) were still alive, and 3 mortalities (20%) occurred. The 1-, 5-, and 10-year overall survival rates after LDLT were 91.7%, 91.7%, and 61.1%, respectively. On multivariate regression analysis, smoking history, operation time, and development of ACR episodes were significant predictors of de novo malignancy development. CONCLUSIONS Liver transplant recipients are at high risk for the development of de novo malignancies. Early detection and aggressive management strategies are essential to improving the recipients' survival.
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Affiliation(s)
- Mohamed Abdel Wahab
- Department of Surgery, Gastrointestinal Surgery Center, College of Medicine, Mansoura University, Egypt
| | | | - Mohamed Elshoubary
- Department of Surgery, Gastrointestinal Surgery Center, College of Medicine, Mansoura University, Egypt
| | - Amr Mohamed Yassen
- Department of Anesthesia and Intensive Care, College of Medicine, Mansoura University, Egypt
| | - Tarek Salah
- Department of Surgery, Gastrointestinal Surgery Center, College of Medicine, Mansoura University, Egypt
| | - Ahmed Mohamed Sultan
- Department of Surgery, Gastrointestinal Surgery Center, College of Medicine, Mansoura University, Egypt
| | - Omar Fathy
- Department of Surgery, Gastrointestinal Surgery Center, College of Medicine, Mansoura University, Egypt
| | - Mohamed Elmorshedi
- Department of Anesthesia and Intensive Care, College of Medicine, Mansoura University, Egypt
| | - Usama Shiha
- Diagnostic & Interventional Radiology Department, Gastrointestinal Surgery Center, College of Medicine, Mansoura University, Egypt
| | - Mohamed Elsadany
- Department of Hepatology, College of Medicine, Mansoura University, Egypt
| | - Reham Adly
- Department of Anesthesia and Intensive Care, College of Medicine, Mansoura University, Egypt
| | - Mohamed Samy
- Department of Anesthesia and Intensive Care, College of Medicine, Mansoura University, Egypt
| | - Ahmed Shehta
- Department of Surgery, Gastrointestinal Surgery Center, College of Medicine, Mansoura University, Egypt.
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20
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Anderson TL, Brandts HM, Gunderson T, Fazzio RT, Hunt KN, Heimbach JK, Glazebrook KN. Breast cancers observed in transplant patients in a single institution. Clin Imaging 2021; 76:26-29. [PMID: 33548889 DOI: 10.1016/j.clinimag.2021.01.029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 01/19/2021] [Accepted: 01/27/2021] [Indexed: 11/16/2022]
Abstract
OBJECTIVE Document occurrence of breast cancer in females after liver, kidney, or pancreas transplantation seen at a tertiary medical center. METHODS Medical records of adult female patients with liver, kidney, or pancreas transplants from 1/1/1995 to 4/4/2014 were retrospectively reviewed. Patients with a history of breast cancer, no mammogram post-transplant, or no research authorization were excluded. Mammogram findings and pathology results were reviewed and recorded. Cancer rates could not be measured in patients followed up outside the institution. Descriptive statistics summarized the cohort. Occurrence rates were estimated using Poisson regression. RESULTS 1095 women were included and 33 were diagnosed with breast cancer post-transplant. Median age at diagnosis was 58 years. Average interval from transplant to cancer diagnosis was 82.6 months. Observed occurrence of invasive and in-situ breast cancer (reported as per 100,000 person-years [95% confidence interval]) was 353 [243-496]. Liver transplant patients showed the lowest rate (181 [95% CI 73-372]), vs. kidney (476 [305-708]) or pancreas (467 [57-1688]). Patients with the highest breast density showed increased occurrence despite younger age (1001 [367-2178]) compared to those with lower breast density (range 239 [109-454] to 372 [186-666]). CONCLUSIONS Female patients after organ transplant experienced increased breast cancer occurrence in this observational study. Those who developed breast cancer also had increased breast density. The findings underscore the importance of breast cancer screening in this population.
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Affiliation(s)
- Tara L Anderson
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States of America.
| | - Hannah M Brandts
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States of America
| | - Tina Gunderson
- Division of Biostatistics and Infomatics, Mayo Clinic, 200 First Street SW, Rochester, MN, United States of America
| | - Robert T Fazzio
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States of America
| | - Katie N Hunt
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States of America
| | - Julie K Heimbach
- Department of Transplantation Surgery, Mayo Clinic, 200 First St SW, Rochester, MN 55905, United States of America
| | - Katrina N Glazebrook
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States of America
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21
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Recalcitrant Esophageal Stricture Secondary to Mycophenolate Mofetil. Case Rep Gastrointest Med 2020; 2020:8817801. [PMID: 33299620 PMCID: PMC7704200 DOI: 10.1155/2020/8817801] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 11/11/2020] [Indexed: 11/17/2022] Open
Abstract
Mycophenolate mofetil (MMF) is associated with various gastrointestinal toxicities. However, limited literature studies exist reporting MMF-related gastrointestinal toxicity manifesting as esophageal strictures. We report a case of a 62-year-old male with kidney transplant on MMF, tacrolimus, and prednisone, presenting with progressive dysphagia and odynophagia. Esophagogastroduodenoscopy revealed severe esophageal stricturing with near food bolus impaction, requiring dilations, esophageal stent, and ultimately gastrostomy tube. Biopsies revealed nonspecific inflammation with no evidence of infectious/neoplastic process; thus, our multidisciplinary esophageal group determined that the process was secondary to MMF. This case demonstrates that, though rare, MMF can result in severe esophageal strictures causing significant morbidity.
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22
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Singh A, De A, Singh V. Post-transplant malignancies in alcoholic liver disease. Transl Gastroenterol Hepatol 2020; 5:30. [PMID: 32258534 DOI: 10.21037/tgh.2019.11.18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2019] [Accepted: 11/21/2019] [Indexed: 01/20/2023] Open
Abstract
Post-transplant malignancy is emerging as an important cause of mortality in patients with cirrhosis undergoing liver transplant (LT). However, establishing the exact relationship between the two needs further evaluation. It has been observed that approximately 30% deaths after 10 years of hepatic transplantation occur due to de novo malignancies. Various known risk factors include immunosuppression, age of patient, alcoholic liver disease (ALD) or primary sclerosing cholangitis, smoking, and oncogenic viral infections. There is scanty literature on the post-transplant malignancy risk in patients with alcoholic cirrhosis. The current evidence suggests a particularly increased risk of oropharyngeal and lung cancers in patients transplanted for ALD. Abstinence from alcohol, smoking and other tobacco-containing products along with optimization of immunosuppression are paramount for decreasing the risk of post-transplant malignancies.
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Affiliation(s)
- Akash Singh
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Arka De
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Virendra Singh
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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23
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Egeli T, Unek T, Ağalar C, Derici S, Ozbilgin M, Akarasu M, Bacakoglu A, Ellidokuz H, Astarcıoglu I. Analysis of Causes and Risk Factors for Late Mortality After Liver Transplant: How Can We Obtain Better Long-Term Survival? EXP CLIN TRANSPLANT 2020; 18:182-187. [PMID: 29863452 DOI: 10.6002/ect.2017.0346] [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] [Indexed: 12/12/2022]
Abstract
OBJECTIVES We investigated late mortality causes and risk factors in patients who were undergoing deceased-donor liver transplant. MATERIALS AND METHODS Patients who had deceased-donor liver transplant from February 1997 to June 2014 in the hepatopancreaticobiliary surgery and liver transplant unit at Dokuz Eylul University Hospital were analyzed. Inclusion criteria were patients over 18 years of age and who survived more than 1 year after liver transplant. Causes of mortality and related risk factors after the first year were analyzed. RESULTS Of the 157 included patients, 102 patients (72%) received transplant procedures for hepatitis B and C secondary to chronic liver disease. Mean follow-up was 89.85 months (range, 14.4-240 months). Of 157 patients, 20 patients (12.7%) died: 12 patients (60%) died during posttransplant years 2-5 and 8 patients (40%) died after 5 years. Causes of death included malignancy in 8 patients (40%), recurrent hepatitis C infection in 3 patients (15%), infection in 3 patients (15%), coronary artery disease in 2 patients (10%), graft rejection in 2 patients (10%), and biliary complications in 2 patients (10%). Univariate analyses showed that long-term survival was significantly lower in patients older than 50 years (P = .001), when there was presence of hepatocellular carcinoma (P = .011), and when donor age was higher than 38 years (P = .045). Multivariate analyses identified recipient age (P = .007) and presence of hepatocellular carcinoma (P = 0.033) as factors that reduced long-term survival. CONCLUSIONS The main causes of late mortality in liver transplant are malignancy, recurrence of hepatitis C, infection, coronary artery disease, graft rejection, and biliary complications. Advanced age and hepatocellular carcinoma are independent risk factors that increase late mortality.
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Affiliation(s)
- Tufan Egeli
- >From the Department of General Surgery, Hepatopancreaticobiliary Surgery and Liver Transplantation Unit, Dokuz Eylul University School of Medicine, Narlıdere, Izmir, Turkey
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24
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Park GC, Hwang S, Ahn CS, Kim KH, Moon DB, Ha TY, Song GW, Jung DH, Yoon YI, Cho HD, Kwon JH, Chung YK, Kang SH, Choi JU, Jung IJ, Lee SG. Pretransplant Hepatic Malignancy Increases Risk of De Novo Malignancy after Liver Transplantation. J Korean Med Sci 2020; 35:e69. [PMID: 32193900 PMCID: PMC7086089 DOI: 10.3346/jkms.2020.35.e69] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Accepted: 01/21/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) recurrence and development of de novo malignancy (DNM) after liver transplantation (LT) are the major causes of late recipient death. METHODS We analyzed the incidence of extrahepatic DNM following living donor LT according to the status of pretransplant hepatic malignancy. We selected 2,076 adult patients who underwent primary LDLT during 7 years from January 2010 to December 2016. RESULTS The pretransplant hepatic malignancy group (n = 1,012) showed 45 cases (4.4%) of the following extrahepatic DNMs: posttransplant lymphoproliferative disease (PTLD) in 10; lung cancer in 10; stomach cancer in 6; colorectal cancer in 5; urinary bladder cancer in 3; and other cancers in 11. The pretransplant no hepatic malignancy group (n = 1,064) showed 25 cases (2.3%) of the following extrahepatic DNMs: colorectal cancer in 3; stomach cancer in 3; leukemia in 3; lung cancer in 3; PTLD in 2; prostate cancer in 2; and other cancers in 9. Incidences of extrahepatic DNM in the pretransplant hepatic malignancy and no hepatic malignancy groups were as follows: 1.1% and 0.5% at 1 year, 3.2% and 2.0% at 3 years, 4.6% and 2.5% at 5 years, and 5.4% and 2.8% at 8 years, respectively (P = 0.006). Their overall patient survival rates were as follows: 97.3% and 97.2% at 1 year, 91.6% and 95.9% at 3 years, 89.8% and 95.4% at 5 years, and 89.2% and 95.4% at 8 years, respectively (P < 0.001). Pretransplant hepatic malignancy was the only significant risk factor for posttransplant extrahepatic DNM. CONCLUSION Our results suggest that patients who had pretransplant hepatic malignancy be followed up more strictly because they have a potential risk of primary hepatic malignancy recurrence as well as a higher risk of extrahepatic DNM than patients without pretransplant hepatic malignancy.
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Affiliation(s)
- Gil Chun Park
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Shin Hwang
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
| | - Chul Soo Ahn
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ki Hun Kim
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Deok Bog Moon
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae Yong Ha
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gi Won Song
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong Hwan Jung
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young In Yoon
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hui Dong Cho
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae Hyun Kwon
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yong Kyu Chung
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang Hyun Kang
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jin Uk Choi
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - I Ji Jung
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Gyu Lee
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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25
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Hussain I, Tasneem F, Gilani US, Arshad MI, Farhan Ul Haque M, Abbas Z, Umer M, Shahzad N. Human BK and JC polyomaviruses: Molecular insights and prevalence in Asia. Virus Res 2020; 278:197860. [PMID: 31911182 DOI: 10.1016/j.virusres.2020.197860] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Revised: 12/31/2019] [Accepted: 01/02/2020] [Indexed: 12/11/2022]
Abstract
Polyomaviridae family consists of small circular dsDNA viruses. Out of the 14 human polyomaviruses described so far, BKPyV and JCPyV have been studied extensively since their discovery in 1971. Reportedly, both BKPyV and JCPyV are widely distributed across the globe with the frequency of 80-90 % in different populations. The primary infection of these viruses is usually asymptomatic and latent which is activated as a consequence of immunosuppression. Activated BKPyV and JCPyV viruses lead to the development of BK Virus Associated Nephropathy and Progressive Multifocal Leukoencephalopathy, respectively. Immense progress has been made during the last few decades regarding the molecular understanding of polyomaviruses. Epidemiology of polyomaviruses has also been studied extensively. However, most of the epidemiological studies have focused on European and American populations. Therefore, limited data is available regarding the geographical distribution of these potentially oncogenic viruses in Asian countries. In this article, we have presented a compendium of latest advances in the molecular understanding of polyomaviruses and their pathobiology. We also present a comprehensive review of published literature regarding the epidemiology and prevalence of BKPyV and JCPyV in Asian regions. For this purpose, a thorough search of available online resources was performed. As a result, we retrieved 24 studies for BKPyV and 22 studies for JCPyV, that describe their prevalence in Asia. These studies unanimously report high occurrence of both BKPyV and JCPyV in Asian populations. The available data from these studies was categorized into two groups: on the basis of prevalence (low, medium and high) and disease development (healthy and diseased). Altogether, Korean population hasbeen evidenced to possess highest frequency of BKPyV (66.7 %), while JCPyV was found to be most prevalent in Taiwan (88 %). Due to high and ubiquitous distribution of these viruses, frequent studies are required to develop a better understanding regarding the epidemiology and pathobiology of these viruses in Asia.
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Affiliation(s)
- Iqra Hussain
- School of Biological Sciences, University of the Punjab, Lahore, Pakistan
| | - Fareeda Tasneem
- Department of Zoology, University of the Punjab, Lahore, Pakistan
| | - Usman Shah Gilani
- School of Biological Sciences, University of the Punjab, Lahore, Pakistan
| | | | | | - Zaigham Abbas
- Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan
| | - Muhammed Umer
- Queensland Micro- and Nanotechnology Centre (QMNC), Griffith University, Nathan, QLD, 4111, Australia
| | - Naveed Shahzad
- School of Biological Sciences, University of the Punjab, Lahore, Pakistan.
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26
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Liu Y, Zhang Y, Ding Y, Chen G, Zhang X, Wang Y, Hua K. Clinical applications of uterus transplantation in China: Issues to take into consideration. J Obstet Gynaecol Res 2020; 46:357-368. [PMID: 31997549 DOI: 10.1111/jog.14199] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Accepted: 12/31/2019] [Indexed: 01/02/2023]
Affiliation(s)
- Yu Liu
- Department of GynecologyThe Obstetrics and Gynecology Hospital of Fudan University Shanghai China
| | - Ying Zhang
- Department of GynecologyThe Obstetrics and Gynecology Hospital of Fudan University Shanghai China
| | - Yan Ding
- Department of GynecologyThe Obstetrics and Gynecology Hospital of Fudan University Shanghai China
| | - Gaowen Chen
- Department of Obstetrics and GynecologyZhujiang Hospital, Southern Medical University Guangzhou China
| | - Xuyin Zhang
- Department of GynecologyThe Obstetrics and Gynecology Hospital of Fudan University Shanghai China
| | - Yifeng Wang
- Department of Obstetrics and GynecologyZhujiang Hospital, Southern Medical University Guangzhou China
| | - Keqin Hua
- Department of GynecologyThe Obstetrics and Gynecology Hospital of Fudan University Shanghai China
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27
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VanHuis A, Loy V. Myth: Liver Transplant Provides a Cure for Liver Disease. Clin Liver Dis (Hoboken) 2019; 13:154-157. [PMID: 31316761 PMCID: PMC6605739 DOI: 10.1002/cld.770] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Accepted: 09/27/2018] [Indexed: 02/04/2023] Open
Affiliation(s)
| | - Veronica Loy
- Department of GastroenterologyEdward Hines Junior VA HospitalHinesIL
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28
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De Caneva A, Porro F, Bortolussi G, Sola R, Lisjak M, Barzel A, Giacca M, Kay MA, Vlahoviček K, Zentilin L, Muro AF. Coupling AAV-mediated promoterless gene targeting to SaCas9 nuclease to efficiently correct liver metabolic diseases. JCI Insight 2019; 5:128863. [PMID: 31211694 DOI: 10.1172/jci.insight.128863] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Non-integrative AAV-mediated gene therapy in the liver is effective in adult patients, but faces limitations in pediatric settings due to episomal DNA loss during hepatocyte proliferation. Gene targeting is a promising approach by permanently modifying the genome. We previously rescued neonatal lethality in Crigler-Najjar mice by inserting a promoterless human uridine glucuronosyl transferase A1 (UGT1A1) cDNA in exon 14 of the albumin gene, without the use of nucleases. To increase recombination rate and therapeutic efficacy, here we used CRISPR/SaCas9. Neonatal mice were transduced with two AAVs: one expressing the SaCas9 and sgRNA, and one containing a promoterless cDNA flanked by albumin homology regions. Targeting efficiency increased ~26-fold with an eGFP reporter cDNA, reaching up to 24% of eGFP-positive hepatocytes. Next, we fully corrected the diseased phenotype of Crigler-Najjar mice by targeting the hUGT1A1 cDNA. Treated mice had normal plasma bilirubin up to 10 months after administration, hUGT1A1 protein levels were ~6-fold higher than in WT liver, with a 90-fold increase in recombination rate. Liver histology, inflammatory markers, and plasma albumin were normal in treated mice, with no off-targets in predicted sites. Thus, the improved efficacy and reassuring safety profile support the potential application of the proposed approach to other liver diseases.
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Affiliation(s)
- Alessia De Caneva
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy
| | - Fabiola Porro
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy
| | - Giulia Bortolussi
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy
| | - Riccardo Sola
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy
| | - Michela Lisjak
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy
| | - Adi Barzel
- Cancer Biology Research Center, Tel Aviv University, Tel Aviv, Israel
| | - Mauro Giacca
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy
| | - Mark A Kay
- Departments of Pediatrics and Genetics, Stanford University, Stanford, California, USA
| | - Kristian Vlahoviček
- Bioinformatics Group, Division of Molecular Biology, Department of Biology, Faculty of Science, University of Zagreb, Zagreb, Croatia
| | - Lorena Zentilin
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy
| | - Andrés F Muro
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy
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29
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Gender, Race and Disease Etiology Predict De Novo Malignancy Risk After Liver Transplantation: Insights for Future Individualized Cancer Screening Guidance. Transplantation 2019; 103:91-100. [PMID: 29377876 DOI: 10.1097/tp.0000000000002113] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Malignancy after liver transplant (LT) is a leading cause of mortality, but data is limited. The aim of this study was to identify patients at higher risk for de novo malignancies after LT in a large multicenter database. METHODS The Scientific Registry of Transplant Recipients database comprising all 108 412 LT recipients across the United States between 1987 and March 2015 was analyzed with a median follow-up of 6.95 years. Potential risk factors for malignancies after LT were assessed using Cox regression analysis for the outcome of time to first malignancy. RESULTS Mean age 51.9 ± 10.8 years, 64.6% male, 74.5% white, and 15.8% with previous malignancy. Malignancies during follow-up were 4,483 (41.3%) skin, 1519 (14.0%) hematologic, and 4842 (44.7%) solid organ. The 10-year probability of de novo malignancy was 11.5% (11.3-11.8%). On multivariable analysis, age by decade (hazard ratio [HR], 1.52; P < 0.001), male sex (HR, 1.28; P < 0.001), white race (compared with other races: HR, 1.45-2.04; P < 0.001), multiorgan transplant (HR, 1.35; P < 0.001), previous malignancy (HR, 1.34; P < 0.001), and alcoholic liver disease, autoimmune, nonalcoholic steatohepatitis (HR, 1.35; P < 0.001), and primary sclerosing cholangitis pre-LT (compared with hepatitis C virus, P < 0.001) were associated with higher risk of post-LT malignancy, but type of immunosuppression was not (P = NS). CONCLUSIONS This large data set demonstrates the effects of ethnicity/race and etiologies of liver disease, particularly nonalcoholic steatohepatitis as additional risk factors for cancer after LT. Patients with these high-risk characteristics should be more regularly and diligently screened.
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30
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DPYD and Fluorouracil-Based Chemotherapy: Mini Review and Case Report. Pharmaceutics 2019; 11:pharmaceutics11050199. [PMID: 31052357 PMCID: PMC6572291 DOI: 10.3390/pharmaceutics11050199] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Revised: 04/19/2019] [Accepted: 04/23/2019] [Indexed: 12/13/2022] Open
Abstract
5-Fluorouracil remains a foundational component of chemotherapy for solid tumour malignancies. While considered a generally safe and effective chemotherapeutic, 5-fluorouracil has demonstrated severe adverse event rates of up to 30%. Understanding the pharmacokinetics of 5-fluorouracil can improve the precision medicine approaches to this therapy. A single enzyme, dihydropyrimidine dehydrogenase (DPD), mediates 80% of 5-fluorouracil elimination, through hepatic metabolism. Importantly, it has been known for over 30-years that adverse events during 5-fluorouracil therapy are linked to high systemic exposure, and to those patients who exhibit DPD deficiency. To date, pre-treatment screening for DPD deficiency in patients with planned 5-fluorouracil-based therapy is not a standard of care. Here we provide a focused review of 5-fluorouracil metabolism, and the efforts to improve predictive dosing through screening for DPD deficiency. We also outline the history of key discoveries relating to DPD deficiency and include relevant information on the potential benefit of therapeutic drug monitoring of 5-fluorouracil. Finally, we present a brief case report that highlights a limitation of pharmacogenetics, where we carried out therapeutic drug monitoring of 5-fluorouracil in an orthotopic liver transplant recipient. This case supports the development of robust multimodality precision medicine services, capable of accommodating complex clinical dilemmas.
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31
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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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Colorectal Cancer Characteristics and Outcomes after Solid Organ Transplantation. JOURNAL OF ONCOLOGY 2019; 2019:5796108. [PMID: 30941176 PMCID: PMC6421000 DOI: 10.1155/2019/5796108] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Revised: 12/09/2018] [Accepted: 02/06/2019] [Indexed: 12/21/2022]
Abstract
Background Individuals after solid organ transplant may develop secondary malignancies. In our clinical practice, we noted an increasing number of individuals who developed colorectal cancers after solid organ transplantation. The primary aim of this study was to describe the characteristics and outcomes of the patients who developed colorectal cancer after solid organ transplant. Materials and Methods Data was gathered and merged from several registries at Mayo Clinic to identify all patients who received a diagnosis of colon or rectal cancer and solid organ transplant. Continuous variables were summarized as mean (standard deviation) and median (range), while categorical variables were reported as frequency (percentage). Time to colorectal cancer after transplant and overall survival after cancer diagnosis were estimated using Kaplan-Meier method. Results Initially, 115 colorectal cancer patients who also had a transplant were identified. The diagnosis of colorectal cancer was noted after solid organ transplant in 63 patients. The mean age at transplant was 57 years. Majority had received a kidney transplant (44.4%) followed by liver (36.5%). The median time to develop colorectal cancer was 59.3 months (range: 4.4-251.4 months). 15 (24.6%) were stage 4 at diagnosis and 13 (21.3%) had stage 3 colorectal cancer. Median overall survival was 30.8 months; 5-, 10- and 15-year survival were noted to be 42.5%, 17.9%, and 7.5%, respectively. None of the stage 4 patients were alive at 5 years; 5-year survival rate for stage 1, 2, and 3 patients was 77%, 50%, and 42%, respectively. Conclusions Our study reports on one of the largest cohorts of patients of colorectal cancer that developed the cancer after solid organ transplant. Survival is extremely poor for advanced cases. However, long-term survivors are noted who developed the cancer at a relatively early stage. Colorectal screening recommendations may need to be revised for patients after solid organ transplant.
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Rompianesi G, Ravikumar R, Jose S, Allison M, Athale A, Creamer F, Gunson B, Manas D, Monaco A, Mirza D, Owen N, Roberts K, Sen G, Srinivasan P, Wigmore S, Fusai G, Fernando B, Burroughs A, Tsochatzis E. Incidence and outcome of colorectal cancer in liver transplant recipients: A national, multicentre analysis on 8115 patients. Liver Int 2019; 39:353-360. [PMID: 30129181 DOI: 10.1111/liv.13947] [Citation(s) in RCA: 8] [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: 02/28/2018] [Revised: 08/02/2018] [Accepted: 08/16/2018] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS De novo malignancies after liver transplantation represent one of the leading causes of death in the long-term. It remains unclear whether liver transplant recipients have an increased risk of colorectal cancer and whether this negatively impacts on survival, particularly in those patients affected by primary sclerosing cholangitis and ulcerative colitis. METHODS In this national multicentre cohort retrospective study, the incidence of colorectal cancer in 8115 evaluable adult patients undergoing a liver transplantation between 1 January 1990 and 31 December 2010 was compared to the incidence in the general population through standardised incidence ratios. RESULTS Fifty-two (0.6%) cases of colorectal cancer were identified at a median of 5.6 years postliver transplantation, predominantly grade 2 (76.9%) and stage T3 (50%) at diagnosis. The incidence rate of colorectal cancer in the whole liver transplant population was similar to the general UK population (SIR: 0.92), but significantly higher (SIR: 7.0) in the group of patients affected by primary sclerosing cholangitis/ulcerative colitis. One-, five- and ten-year survival rates from colorectal cancer diagnosis were 71%, 48% and 31%, respectively, and the majority of colorectal cancer patients died of cancer-specific causes. CONCLUSIONS Liver transplantation alone is not associated with an increased risk of colorectal cancer development. The primary sclerosing cholangitis/ulcerative colitis liver transplant population showed a significantly higher risk of colorectal cancer development than the general population, with a high proportion of advanced stage at diagnosis and a reduced patient survival.
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Affiliation(s)
- Gianluca Rompianesi
- Sheila Sherlock Liver Unit, UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Reena Ravikumar
- Sheila Sherlock Liver Unit, UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Sophie Jose
- Research Department of Infection and Population Health, University College London, London, UK
| | - Michael Allison
- Cambridge Transplant Unit, Cambridge Biomedical Research Centre, Cambridge University Hospitals, Cambridge, UK
| | - Anuja Athale
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Felicity Creamer
- Department of HPB and Transplant Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Bridget Gunson
- The Liver Unit, University Hospitals Birmingham and NIHR Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, UK
| | - Derek Manas
- Institute of Transplantation, Freeman Hospital, Newcastle, UK
| | - Andrea Monaco
- Sheila Sherlock Liver Unit, UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Darius Mirza
- The Liver Unit, University Hospitals Birmingham and NIHR Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, UK
| | - Nicola Owen
- Cambridge Transplant Unit, Cambridge Biomedical Research Centre, Cambridge University Hospitals, Cambridge, UK
| | - Keith Roberts
- The Liver Unit, University Hospitals Birmingham and NIHR Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, UK
| | - Gourab Sen
- Institute of Transplantation, Freeman Hospital, Newcastle, UK
| | | | - Stephen Wigmore
- Department of HPB and Transplant Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Giuseppe Fusai
- Sheila Sherlock Liver Unit, UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Bimbi Fernando
- Sheila Sherlock Liver Unit, UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Andrew Burroughs
- Sheila Sherlock Liver Unit, UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Emmanuel Tsochatzis
- Sheila Sherlock Liver Unit, UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
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González JP, Zabaleta A, Sangro P, Basualdo JE, Burgos L, Paiva B, Herrero JI. Immunophenotypic Pattern of De Novo Malignancy After Liver Transplantation. Transplant Proc 2019; 51:77-79. [PMID: 30655139 DOI: 10.1016/j.transproceed.2018.04.090] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Revised: 04/12/2018] [Accepted: 04/27/2018] [Indexed: 10/27/2022]
Abstract
Long-term survival after liver transplantation is affected by de novo neoplasia. The incidence of this type of malignancy is increased in the setting of immunosuppressive therapy. The aim of this study was to characterize the immunologic pattern of liver transplant recipients with de novo malignancies. Fifty-one liver recipients were studied, 19 of whom had a history of de novo neoplasia. Immunophenotypic patterns among patients with/without tumors were compared. The subpopulations of CD4+ T lymphocytes and CD8+ T lymphocytes differed between the 2 types of patients studied. In patients with tumor, activation membrane markers in CD4+ T lymphocytes and CD8+ T-lymphocytes, such as CD56 or CD25, were expressed in a greater proportion, whereas activation markers CD314 and CD16 were reduced in CD56bright natural killer (NK) cells. We concluded that cytotoxic response seems to be more activated in de novo neoplasia patients, which highlights the still unknown malignancy risk effect on these immune cells.
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Affiliation(s)
- J P González
- School of Medicine, University of Navarra, Pamplona, Navarra, Spain
| | - A Zabaleta
- Flow Cytometry Core, Centro de Investigación Médica Aplicada, Pamplona, Navarra, Spain
| | - P Sangro
- Department of Internal Medicine, Clínica Universidad de Navarra, IDISNA, Pamplona, Navarra, Spain
| | - J E Basualdo
- Liver Unit, Clínica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra and Centro de Investigación Biomédica de enfermedades hepáticas y Digestivas, Pamplona, Navarra, Spain
| | - L Burgos
- Flow Cytometry Core, Centro de Investigación Médica Aplicada, Pamplona, Navarra, Spain
| | - B Paiva
- Flow Cytometry Core, Centro de Investigación Médica Aplicada, Pamplona, Navarra, Spain
| | - J I Herrero
- Department of Internal Medicine, Clínica Universidad de Navarra, IDISNA, Pamplona, Navarra, Spain; Liver Unit, Clínica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra and Centro de Investigación Biomédica de enfermedades hepáticas y Digestivas, Pamplona, Navarra, Spain.
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Bilirubin-Induced Oxidative Stress Leads to DNA Damage in the Cerebellum of Hyperbilirubinemic Neonatal Mice and Activates DNA Double-Strand Break Repair Pathways in Human Cells. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2018; 2018:1801243. [PMID: 30598724 PMCID: PMC6287157 DOI: 10.1155/2018/1801243] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 09/19/2018] [Accepted: 10/02/2018] [Indexed: 12/27/2022]
Abstract
Unconjugated bilirubin is considered a potent antioxidant when present at moderate levels. However, at high concentrations, it produces severe neurological damage and death associated with kernicterus due to oxidative stress and other mechanisms. While it is widely recognized that oxidative stress by different toxic insults results in severe damage to cellular macromolecules, especially to DNA, no data are available either on DNA damage in the brain triggered by hyperbilirubinemia during the neonatal period or on the activation of DNA repair mechanisms. Here, using a mouse model of neonatal hyperbilirubinemia, we demonstrated that DNA damage occurs in vivo in the cerebellum, the brain region most affected by bilirubin toxicity. We studied the mechanisms associated with potential toxic action of bilirubin on DNA in in vitro models, which showed significant increases in DNA damage when neuronal and nonneuronal cells were treated with 140 nM of free bilirubin (Bf), as determined by γH2AX Western blot and immunofluorescence analyses. Cotreatment of cells with N-acetyl-cysteine, a potent oxidative-stress inhibitor, prevented DNA damage by bilirubin, supporting the concept that DNA damage was caused by bilirubin-induced oxidative stress. Bilirubin treatment also activated the main DNA repair pathways through homologous recombination (HR) and nonhomologous end joining (NHEJ), which may be adaptive responses to repair bilirubin-induced DNA damage. Since DNA damage may be another important factor contributing to neuronal death and bilirubin encephalopathy, these results contribute to the understanding of the mechanisms associated with bilirubin toxicity and may be of relevance in neonates affected with severe hyperbilirubinemia.
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Kang EA, Koh SJ, Kim JW, Lee KL, Im JP, Kim JS, Kim BG. Prevalence of advanced colorectal neoplasm is higher in liver transplant recipients. TURKISH JOURNAL OF GASTROENTEROLOGY 2018; 29:316-324. [PMID: 29755016 DOI: 10.5152/tjg.2018.17458] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND/AIMS Patients with liver transplantation are at increased risk of developing new malignancy because of the prolonged immunosuppression after transplantation. The aims of this study were to investigate whether advanced colorectal neoplasms occurs more in liver transplant recipients compared to healthy individuals and to evaluate the effect of immunosuppression on advanced colorectal neoplasia. MATERIALS AND METHODS This was a retrospective, single-centered, case-control study. We reviewed 348 liver transplant patients who had undergone a colonoscopy after liver transplantation from 1991 to 2012. Healthy controls from asymptomatic individuals who had undergone colonoscopy for screening purposes were randomly selected and reviewed. RESULTS Advanced colorectal neoplasms were identified in 17 of the 348 patients (4.9%). The risk of advanced colorectal neoplasia was 3.6 times greater in liver transplant patients (odds ratio [OR] 3.578; 95% confidence interval [CI] 1.578-8.115; p=0.001). The risk of developing colon cancer was 8.4 times higher in transplant patients (OR 8.416; 95% CI 1.808-39.172; p=0.001). CONCLUSION Liver transplant recipients were at a high risk of colorectal cancer. Therefore, colonoscopy surveillance after liver transplantation is recommended. Immunosuppressive therapy could facilitate carcinogenesis.
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Affiliation(s)
- Eun Ae Kang
- Department of Internal Medicine and Liver Research Institute, Seoul National University School of Medicine, Seoul, Korea
| | - Seong-Joon Koh
- Department of Internal Medicine, Seoul National University Boramae Hospital, Seoul National University School of Medicine, Seoul, Korea
| | - Ji Won Kim
- Department of Internal Medicine, Seoul National University Boramae Hospital, Seoul National University School of Medicine, Seoul, Korea
| | - Kook Lae Lee
- Department of Internal Medicine, Seoul National University Boramae Hospital, Seoul National University School of Medicine, Seoul, Korea
| | - Jong Pil Im
- Department of Internal Medicine and Liver Research Institute, Seoul National University School of Medicine, Seoul, Korea
| | - Joo Sung Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University School of Medicine, Seoul, Korea
| | - Byeong Gwan Kim
- Department of Internal Medicine, Seoul National University Boramae Hospital, Seoul National University School of Medicine, Seoul, Korea
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Bernal Bellido C, Suárez Artacho G, Álamo Martínez JM, Marin Gómez LM, Cepeda Franco C, Barrera Pulido L, Praena Fernández JM, Padillo Ruiz J, Gómez Bravo MÁ. Incidencia y supervivencia de los tumores de novo en el trasplante hepático. Cir Esp 2018; 96:501-507. [DOI: 10.1016/j.ciresp.2018.05.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Revised: 03/10/2018] [Accepted: 05/04/2018] [Indexed: 12/11/2022]
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Bhat M, Mara K, Dierkhising R, Watt KDS. Immunosuppression, Race, and Donor-Related Risk Factors Affect De novo Cancer Incidence Across Solid Organ Transplant Recipients. Mayo Clin Proc 2018; 93:1236-1246. [PMID: 30064826 DOI: 10.1016/j.mayocp.2018.04.025] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Revised: 04/14/2018] [Accepted: 04/20/2018] [Indexed: 02/08/2023]
Abstract
OBJECTIVE To analyze immunosuppression regimens, demographic characteristics such as race, and donor features across solid organ transplant (SOT) recipients to provide better insight into their effect on the increased cancer risk in SOT. PATIENTS AND METHODS We analyzed the Scientific Registry of Transplant Recipients database comprising 534,472 SOT recipients across the United States from October 1, 1987, through March 31, 2015. RESULTS In total, 53,783 de novo malignancies were identified. Overall 15-year incidence of malignancies was 13.2% (95% CI, 13.0%-13.4%) for kidney ± pancreas, 17.9% (95% CI, 15.9%-19.8%) for pancreas alone, 15.2% (95% CI, 14.9%-15.5%) for liver, 28.1% (95% CI, 27.5%-28.7%) for heart, and 25.6% (95% CI, 24.8%-26.3%) for lung recipients. Relative to kidney ± pancreas transplant, other SOT recipients (except liver) experienced higher risk. On multivariable analysis, use of 2 or more immunosuppressant agents (P<.001), older age (P<.001), male sex (P<.001), white race (P<.001), previous malignancy (P<.001), older donor age (P=.003), and white donor race (P=.03) increased de novo malignancy, whereas mammalian target of rapamycin inhibitor use decreased risk (P=.01), driven by a reduction in skin cancer. CONCLUSION Malignancy risk varies across SOT groups and correlates with the number of immunosuppressant drugs used. Mammalian target of rapamycin inhibitor-based immunosuppression seems protective against nonmelanoma skin cancer only. Cancer risk may be improved by minimizing the number of immunosuppressants and the degree of immunosuppression used, particularly in at-risk patients. Increased age, male sex, previous malignancy, and white race are characteristics that should prompt heightened vigilance in cancer screening by transplant physicians and internists who follow this patient population.
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Affiliation(s)
- Mamatha Bhat
- Division of Gastroenterology and Hepatology, University Health Network and University of Toronto, Toronto, ON, Canada; Multiorgan Transplant Program, University Health Network, Toronto, ON, Canada
| | - Kristin Mara
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN
| | - Ross Dierkhising
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN
| | - Kymberly D S Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
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Bortolussi G, Muro AF. Advances in understanding disease mechanisms and potential treatments for Crigler–Najjar syndrome. Expert Opin Orphan Drugs 2018. [DOI: 10.1080/21678707.2018.1495558] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Giulia Bortolussi
- Mouse Molecular Genetics Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy
| | - Andrés Fernando Muro
- Mouse Molecular Genetics Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy
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40
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Thursz M, Gual A, Lackner C, Mathurin P, Moreno C, Spahr L, Sterneck M, Cortez-Pinto H. EASL Clinical Practice Guidelines: Management of alcohol-related liver disease. J Hepatol 2018; 69:154-181. [PMID: 29628280 DOI: 10.1016/j.jhep.2018.03.018] [Citation(s) in RCA: 573] [Impact Index Per Article: 81.9] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 03/20/2018] [Indexed: 12/12/2022]
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41
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Wan DL, Li MX, Bao L, Zhang LL, Zhang L, Chen QY, Lin SZ. Cauliflower-like Neoplasm of Duodenal Papilla in a Liver Transplant Recipient: What Should We Think and Do? A Case Report. Transplant Proc 2018; 50:925-929. [PMID: 29661464 DOI: 10.1016/j.transproceed.2018.01.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2018] [Accepted: 01/29/2018] [Indexed: 11/30/2022]
Abstract
BACKGROUND With the continuous improvement of liver transplantation technology, the survival rate of liver transplantation has been improved, but recurrent or de novo malignancy remains one of the major factors affecting the long-term survival of liver transplant recipients. CASE REPORT A 45-year-old Chinese man had a plastic biliary stent placed on account of biliary anastomotic stenosis after 3 years of piggyback liver transplantation. He came to our hospital because of recurrent fever and jaundice for 2 weeks, and his carcinoembryonic antigen-199 had increased. The patient's duodenal papillary was cauliflower-like at endoscopic retrograde cholangiopancreatography to replace the biliary stent. He was initially suspected of having duodenal papillary carcinoma after liver transplantation. However, the pathology from endoscopic retrograde cholangiopancreatography and endoscopic ultrasound-guided biopsy showed inflammation. While awaiting the result of biopsy, his CA-199 decreased significantly after anti-infection and symptomatic treatment. The patient was diagnosed with biliary anastomotic stenosis and duodenal papillitis. He was discharged uneventfully; to date, there is no evidence of malignant tumor. CONCLUSIONS We report this case to provide helpful information to clinicians about the management of the duodenal papilla cauliflower-like neoplasm after liver transplantation, which should be considered as inflammatory first. Perhaps our view can avoid the risk of bringing an excessive medical treatment and unnecessary economic burden to patients and their families.
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Affiliation(s)
- D-L Wan
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - M-X Li
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - L Bao
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - L-L Zhang
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - L Zhang
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Q-Y Chen
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - S-Z Lin
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
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Tartarone A, Romano G, Galasso R, Coccaro M, Cammarota A, Sgambato A, Bochicchio A. Pulmonary Blastoma after Liver Transplant: A Case Report. TUMORI JOURNAL 2018; 88:173-5. [PMID: 12088262 DOI: 10.1177/030089160208800219] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
There is an increased risk of cancer after organ transplantation mainly due to the immunosuppressive therapy required in these patients. We report a case of biphasic pulmonary blastoma in an adult male who underwent liver transplant for hepatocellular carcinoma in March 1999, followed by immunosuppressive treatment and adjuvant chemotherapy with epirubicin. Disease-free survival lasted 18 months, then a diagnosis of biphasic pulmonary blastoma was made and the patient underwent a lung lobectomy. Five months after surgical resection a recurrence of this rare tumor was recorded and two cycles of cisplatin + etoposide and ifosfamide + etoposide and one cycle of second-line chemotherapy with vinorelbine were administered. The tolerability and the efficacy of this treatment were poor. The patient died less than one year after diagnosis. To our knowledge this is the first reported case of pulmonary blastoma in a transplant patient. Our findings confirm that organ transplant recipients deserve long-term medical surveillance also in the absence of graft complications, and that pulmonary blastoma is an aggressive tumor with a poor prognosis.
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Affiliation(s)
- Alfredo Tartarone
- Department of Medical Oncology, Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture (PZ), Italy.
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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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Tanaka T, Voigt MD. Decision tree analysis to stratify risk of de novo non-melanoma skin cancer following liver transplantation. J Cancer Res Clin Oncol 2018; 144:607-615. [PMID: 29362916 DOI: 10.1007/s00432-018-2589-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2017] [Accepted: 01/17/2018] [Indexed: 01/15/2023]
Abstract
PURPOSE Non-melanoma skin cancer (NMSC) is the most common de novo malignancy in liver transplant (LT) recipients; it behaves more aggressively and it increases mortality. We used decision tree analysis to develop a tool to stratify and quantify risk of NMSC in LT recipients. METHODS We performed Cox regression analysis to identify which predictive variables to enter into the decision tree analysis. Data were from the Organ Procurement Transplant Network (OPTN) STAR files of September 2016 (n = 102984). RESULTS NMSC developed in 4556 of the 105984 recipients, a mean of 5.6 years after transplant. The 5/10/20-year rates of NMSC were 2.9/6.3/13.5%, respectively. Cox regression identified male gender, Caucasian race, age, body mass index (BMI) at LT, and sirolimus use as key predictive or protective factors for NMSC. These factors were entered into a decision tree analysis. The final tree stratified non-Caucasians as low risk (0.8%), and Caucasian males > 47 years, BMI < 40 who did not receive sirolimus, as high risk (7.3% cumulative incidence of NMSC). The predictions in the derivation set were almost identical to those in the validation set (r2 = 0.971, p < 0.0001). Cumulative incidence of NMSC in low, moderate and high risk groups at 5/10/20 year was 0.5/1.2/3.3, 2.1/4.8/11.7 and 5.6/11.6/23.1% (p < 0.0001). CONCLUSIONS The decision tree model accurately stratifies the risk of developing NMSC in the long-term after LT.
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Affiliation(s)
- Tomohiro Tanaka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA, USA.
| | - Michael D Voigt
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA, USA
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Arinaga-Hino T, Ide T, Miyajima I, Ogata K, Kuwahara R, Amano K, Kawaguchi T, Nakamura T, Kawaguchi T, Koga H, Yonemoto K, Torimura T. Risk of malignancies in autoimmune hepatitis type 1 patients with a long-term follow-up in Japan. Hepatol Res 2018; 48:E222-E231. [PMID: 28841782 DOI: 10.1111/hepr.12973] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Revised: 08/18/2017] [Accepted: 08/21/2017] [Indexed: 02/08/2023]
Abstract
AIM The risk of malignancies in autoimmune diseases is high and is regarded to be due to immunological abnormalities, the use of immunosuppressive agents, and/or chronic inflammation. The aim of this study was to investigate the incidence and risk of malignancies in patients with autoimmune hepatitis (AIH) type 1 in Japan. METHODS Two hundred and fifty-six patients diagnosed with AIH were enrolled. A person-year calculation was carried out for AIH patients, and the numbers of expected events were clarified using data from "The Monitoring of Cancer Incidence in Japan Project" in order to examine the standard incident rate (SIR) of each type of malignancy. Biochemical data regarding carcinogenesis and its background factors were also examined. RESULTS Twenty-seven patients (10.5%) developed malignancies; 11 (4.3%) with hepatobiliary cancer and 16 (6.3%) with extrahepatic malignancies. The overall SIR for malignancies in AIH was significantly high at 2.04 (95% confidence interval [CI], 1.34-2.96), and was high among female patients at 2.49 (95% CI, 1.60-3.71). The SIR for hepatobiliary cancer was 14.14 (95% CI, 7.05-25.30), and was markedly high for female patients at 21.83 (95% CI, 10.45-40.16). The SIR for oral/pharyngeal cancer was significantly high for female patients at 14.61 (95% CI, 1.64-52.77). The risk factors for hepatobiliary cancer at the diagnosis of AIH were low levels of alanine aminotransferase (P = 0.0226), low platelet counts (P < 0.0001), and cirrhosis (P = 0.0004). The risk factor for extrahepatic malignancy was relapse of AIH (P = 0.0485). CONCLUSION The risk of malignancies was generally high among AIH patients. Those with the risk factors of malignancies should be carefully followed up.
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Affiliation(s)
- Teruko Arinaga-Hino
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Tatsuya Ide
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Ichiro Miyajima
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Kei Ogata
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Reiichiro Kuwahara
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Keisuke Amano
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Toshihiro Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Toru Nakamura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Hironori Koga
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Koji Yonemoto
- The Biostatistics Center, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Takuji Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
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Karakoyun M, Önen Ş, Baran M, Çakır M, Ecevit ÇÖ, Kılıç M, Kantar M, Aksoylar S, Özgenç F, Aydoğdu S. Post-transplant malignancies in pediatric liver transplant recipients: Experience of two centers in Turkey. THE TURKISH JOURNAL OF GASTROENTEROLOGY : THE OFFICIAL JOURNAL OF TURKISH SOCIETY OF GASTROENTEROLOGY 2018; 29:89-93. [PMID: 29391313 PMCID: PMC6322611 DOI: 10.5152/tjg.2017.17089] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Accepted: 08/15/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND/AIMS A liver transplant is the preferred treatment for patients with end-stage liver disease, as it usually results in longterm survival. However, due to the use of chronic immunosuppressive therapy, which is necessary to prevent rejection, de novo cancer is a major risk after transplantation. The aim of this study was to assess the incidence of post-transplant malignancies in children after liver transplantations. MATERIALS AND METHODS The study group consisted of 206 liver transplant recipients, with no history of cancer, including hepatocellular carcinoma, in two liver transplantation centers in Turkey between 1997 and 2015. Data were obtained from patient's data chart. RESULTS In the study group, de novo cancer was diagnosed in 13 of the 206 patients. Post-transplant lymphoproliferative disease (PTLD) occurred in seven (53.8%) patients and other malignancies in six of the 13 patients. The types of PTLD were as follows: B-cell origin (n=2), Epstein-Barr virus (EBV)-related (n=2), T-cell origin (n=1), and Hodgkin's lymphoma (n=2). EBV DNA was isolated from seven patients, three of whom developed PTLD. The others developed Kaposi's sarcomas, Burkitt's lymphomas, cutaneous large-cell lymphomas, Hodgkin's lymphomas, and liver sarcomas. CONCLUSION After transplantation, immunosuppressive treatment is unavoidable, increasing the risk of malignancies. However, a close follow-up and periodic screening can reduce cancer-related mortality and morbidity.
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Affiliation(s)
- Miray Karakoyun
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Tepecik Training and Research Hospital, İzmir, Turkey
| | - Şebnem Önen
- Department of Pediatrics, Ege University School of Medicine, İzmir, Turkey
| | - Maşallah Baran
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Katip Celebi University School of Medicine, İzmir, Turkey
| | - Murat Çakır
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Karadeniz Technical University School of Medicine, Trabzon Turkey
| | - Çiğdem Ömür Ecevit
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Prof. Dr. Behçet Uz Children’s Hospital, İzmir, Turkey
| | - Murat Kılıç
- Department of Transplantation and General Surgery, Kent Hospital, İzmir, Turkey
| | - Mehmet Kantar
- Department of Pediatric Oncology, Ege University School of Medicine, İzmir, Turkey
| | - Serap Aksoylar
- Department of Pediatric Oncology, Ege University School of Medicine, İzmir, Turkey
| | - Funda Özgenç
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Ege University School of Medicine, İzmir, Turkey
| | - Sema Aydoğdu
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Ege University School of Medicine, İzmir, Turkey
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Rademacher S, Seehofer D, Eurich D, Schoening W, Neuhaus R, Oellinger R, Denecke T, Pascher A, Schott E, Sinn M, Neuhaus P, Pratschke J. The 28-year incidence of de novo malignancies after liver transplantation: A single-center analysis of risk factors and mortality in 1616 patients. Liver Transpl 2017; 23:1404-1414. [PMID: 28590598 DOI: 10.1002/lt.24795] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Revised: 05/08/2017] [Accepted: 05/14/2017] [Indexed: 12/13/2022]
Abstract
De novo malignancies (DNMs) are one of the leading causes of late mortality after liver transplantation (LT). We analyzed 1616 consecutive patients who underwent LT between 1988 and 2006 at our institution. All patients were prospectively observed over a study period of 28 years by our own outpatient clinic. Complete follow-up data were available for 96% of patients, 3% were incomplete, and only 1% were lost to follow-up. The median follow-up of the patients was 14.1 years. Variables with possible prognostic impact on the development of DNMs were analyzed, as was the incidence of malignancies compared with the nontransplant population by using standardized incidence ratios. In total, 266 (16.5%) patients developed 322 DNMs of the following subgroups: hematological malignancies (n = 49), skin cancer (n = 83), and nonskin solid organ tumors (SOT; n = 190). The probability of developing any DNM within 10 and 25 years was 12.9% and 23.0%, respectively. The respective probability of developing SOT was 7.8% and 16.2%. Mean age at time of diagnosis of SOT was 57.4 years (range, 18.3-81.1 years). In the multivariate analysis, an increased recipient age (hazard ratio [HR], 1.03; P < 0.001) and a history of smoking (HR, 1.92; P < 0.001) were significantly associated with development of SOT. Moreover, the development of SOT was significantly increased in cyclosporine A-treated compared with tacrolimus-treated patients (HR, 1.53; P = 0.03). The present analysis shows a disproportionate increase of de novo SOT with an increasing follow-up period. Increased age and a history of smoking are confirmed as major risk factors. Moreover, the importance of immunosuppression is highlighted. Liver Transplantation 23 1404-1414 2017 AASLD.
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Affiliation(s)
- Sebastian Rademacher
- Departments of Surgery, Campus Charité Mitte and Campus Virchow Klinikum.,Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, Leipzig, Germany
| | - Daniel Seehofer
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, Leipzig, Germany
| | - Dennis Eurich
- Departments of Surgery, Campus Charité Mitte and Campus Virchow Klinikum
| | - Wenzel Schoening
- Department of General, Visceral and Transplantation Surgery, University Hospital Aachen, Aachen, Germany
| | - Ruth Neuhaus
- Departments of Surgery, Campus Charité Mitte and Campus Virchow Klinikum
| | - Robert Oellinger
- Departments of Surgery, Campus Charité Mitte and Campus Virchow Klinikum
| | | | - Andreas Pascher
- Departments of Surgery, Campus Charité Mitte and Campus Virchow Klinikum
| | | | - Mariann Sinn
- Hematology and Oncology, Charité Campus Virchow, Universitätsmedizin Berlin, Berlin, Germany
| | - Peter Neuhaus
- Departments of Surgery, Campus Charité Mitte and Campus Virchow Klinikum
| | - Johann Pratschke
- Departments of Surgery, Campus Charité Mitte and Campus Virchow Klinikum
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Prenner S, Levitsky J. Comprehensive Review on Colorectal Cancer and Transplant. Am J Transplant 2017; 17:2761-2774. [PMID: 28471512 DOI: 10.1111/ajt.14340] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2017] [Revised: 04/19/2017] [Accepted: 04/23/2017] [Indexed: 01/25/2023]
Abstract
Colorectal cancer (CRC) is a common malignancy worldwide. Some studies suggest that organ recipients are at a higher risk for CRC than the general population. The underlying transplant indications and their inherent risk factors for CRC may drive the variation in incidence rates that are seen in patients receiving different allografts. Recipients with cystic fibrosis are now recognized as a population at high risk for CRC at a young age. Transplant recipients have high mortality following a CRC diagnosis, even if it is detected at an early stage. Certain types of immunosuppression have been shown to accelerate cancer transformation and may contribute to the more aggressive phenotype seen in organ recipients. Given the high incidence and progressive nature of posttransplant CRC, shorter screening intervals with a modality that can detect early-stage polyps may be essential to prevent mortality. Future research is needed to better elucidate the role of immunosuppression in carcinogenesis. This comprehensive review examines CRC risk, screening, and management specific to organ transplant candidates and recipients.
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Affiliation(s)
- S Prenner
- Division of Gastroenterology & Hepatology, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - J Levitsky
- Division of Gastroenterology & Hepatology, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL
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Izzy M, Watt KD. The reality of de novo malignancy: Sadly, not fake news. Liver Transpl 2017; 23:1367-1368. [PMID: 28921889 DOI: 10.1002/lt.24869] [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: 09/11/2017] [Accepted: 09/11/2017] [Indexed: 01/13/2023]
Affiliation(s)
- Manhal Izzy
- Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, MN
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, MN
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Madeleine M, Patel N, Plasmeijer E, Engels E, Bouwes Bavinck J, Toland A, Green A. Epidemiology of keratinocyte carcinomas after organ transplantation. Br J Dermatol 2017; 177:1208-1216. [DOI: 10.1111/bjd.15931] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/23/2017] [Indexed: 12/14/2022]
Affiliation(s)
| | - N.S. Patel
- University of South Florida Tampa FL U.S.A
| | - E.I. Plasmeijer
- QIMR Berghofer Medical Research Institute Queensland Australia
| | | | | | - A.E. Toland
- The Ohio State University Medical Center Columbus OH U.S.A
| | - A.C. Green
- QIMR Berghofer Medical Research Institute Queensland Australia
- CRUK Manchester Institute and University of Manchester Manchester Academic Health Sciences Centre Manchester U.K
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