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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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Fadlallah H, El Masri D, Bahmad HF, Abou-Kheir W, El Masri J. Update on the Complications and Management of Liver Cirrhosis. Med Sci (Basel) 2025; 13:13. [PMID: 39982238 PMCID: PMC11843904 DOI: 10.3390/medsci13010013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2025] [Revised: 02/01/2025] [Accepted: 02/02/2025] [Indexed: 02/22/2025] Open
Abstract
Liver cirrhosis represents the advanced pathological stage of chronic liver disease, characterized by the progressive destruction and regeneration of the hepatic parenchyma over years, culminating in fibrosis and disruption of the vascular architecture. As a leading global cause of morbidity and mortality, it continues to affect millions worldwide, imposing a substantial burden on healthcare systems. Alcoholic/nonalcoholic fatty liver disease and chronic viral hepatitis infection, hepatitis C (HCV) in particular, remain leading causes of cirrhosis. Despite significant advances in understanding the pathogenesis of cirrhosis, its management is still complex due to the multifaceted complications, including ascites, hepatic encephalopathy, variceal bleeding, and hepatocellular carcinoma, all of which severely compromise the patient outcomes and quality of life. This review aims at filling a critical gap by providing a comprehensive summary of the latest evidence on the complications and management of liver cirrhosis. Evidence-based therapies targeting both the etiologies and complications of cirrhosis are essential for improving outcomes. While liver transplantation is considered a definitive cure, advancements in pharmacological therapies offer promising avenues for halting and potentially reversing disease progression. This review summarizes the latest management strategies for cirrhosis and its associated complications, emphasizing the importance of early intervention and novel therapeutic options for improving outcomes and quality of life in affected individuals.
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Affiliation(s)
- Hiba Fadlallah
- Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon; (H.F.); (J.E.M.)
| | - Diala El Masri
- Faculty of Medicine, University of Balamand, Al-Kurah, Tripoli P.O. Box 100, Lebanon;
| | - Hisham F. Bahmad
- Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA;
| | - Wassim Abou-Kheir
- Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon; (H.F.); (J.E.M.)
| | - Jad El Masri
- Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon; (H.F.); (J.E.M.)
- Faculty of Medical Sciences, Lebanese University, Beirut 1107-2020, Lebanon
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Bittencourt PL, Nardelli MJ, Barros LL, Cançado GGL, Cançado ELR, Terrabuio DRB, Villela-Nogueira CA, Ferraz MLG, Codes L, Rotman V, Rocco R, Felga GE, Dotta DD, Martins ADS, Mendes LSC, da Silva MC, Hyppolito EB, Gomide GPM, Signorelli IV, de Oliveira MB, Ivantes CAP, Chindamo MC, de Almeida E Borges VF, Faria LC, Couto CA. Recurrence of Primary Sclerosing Cholangitis and De Novo Cholangiocarcinoma After Liver Transplantation: Results From the Brazilian Cholestasis Consortium. Clin Transplant 2024; 38:e70002. [PMID: 39436152 DOI: 10.1111/ctr.70002] [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: 10/30/2023] [Revised: 07/21/2024] [Accepted: 10/04/2024] [Indexed: 10/23/2024]
Abstract
BACKGROUND AND AIM Primary sclerosing cholangitis (PSC) has been shown to recur after liver transplantation (LT). Some studies have identified certain clinical and laboratory variables associated with an increased risk for recurrent PSC (rPSC) in Caucasians. Furthermore, de novo cholangiocarcinoma (CCA) has been reported anecdotally in patients with rPSC. This study aims to assess the prevalence of rPSC, identify its associated risk factors, and investigate the occurrence of de novo CCA in a highly admixed population from Brazil. METHODS All patients submitted to LT for PSC enrolled in the Brazilian Cholestasis Study Group database were retrospectively reviewed for the occurrence of rPSC and de novo CCA. RESULTS Ninety-six (58 males, mean age 32 ± 13 years) patients with PSC underwent LT. After 90 (39-154) months of follow-up (FU), rPSC was observed in 29 (30%) subjects. There were no significant associations between rPSC and age, gender, concurrent or de novo inflammatory bowel disease, MELD score at the time of LT or allograft rejection. The only factor associated with an increased risk of disease recurrence was time after LT. Although survival was decreased in patients who developed rPSC, this difference was not significant. Only one female patient developed de novo CCA after rPSC, 11 years after LT. CONCLUSIONS Recurrent PSC was observed in one-third of PSC LT patients in Brazil and was associated with longer time after LT. Despite its frequency, rPSC was not associated with a higher risk of graft loss or a significant reduction in posttransplant survival.
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Affiliation(s)
- Paulo Lisboa Bittencourt
- Hospital Português, Salvador, Brazil
- Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil
| | | | - Luísa Leite Barros
- Departamento de Gastroenterologia, Universidade de São Paulo, São Paulo, Brazil
| | - Guilherme Grossi Lopes Cançado
- Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
- Hospital da Polícia Militar de Minas Gerais, Belo Horizonte, Brazil
| | | | | | | | | | | | - Vivian Rotman
- Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Rodrigo Rocco
- Hospital Israelita Albert Einsten, São Paulo, Brazil
| | | | - Diogo Delgado Dotta
- Departamento de Gastroenterologia, Universidade de São Paulo, São Paulo, Brazil
| | | | | | | | | | | | | | | | | | - Maria Chiara Chindamo
- Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- Hospital Barra D´or - Rede D´or São Luiz, Rio de Janeiro, Brazil
| | | | - Luciana Costa Faria
- Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Claudia Alves Couto
- Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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Ruijter BN, Tushuizen ME, van der Helm D, Hew M, Reeven M, Vossen ACTM, Metselaar HJ, Alwayn IPJ, Dubbeld J, Polak WG, van Hoek B. Primary sclerosing cholangitis and other risk factors for post-transplant lymphoproliferative disease after liver transplantation in adults. Liver Transpl 2024; 30:640-646. [PMID: 37698933 DOI: 10.1097/lvt.0000000000000256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Accepted: 08/27/2023] [Indexed: 09/14/2023]
Abstract
Post-transplant lymphoproliferative disease (PTLD) is a rare but serious complication of liver transplantation (LT) with morbidity and mortality. The risk factors for PTLD in adults are ill-defined. This study aimed to assess the risk factors for PTLD after LT in adults. All adult LT recipients between 1986 and 2016 from 2 centers in the Netherlands were included, with follow-up until 2020. PTLD was diagnosed according to the World Health Organization (WHO) classification. Potential risk factors for PTLD were assessed using multivariate Cox regression analysis. A total of 1281 patients were included, of whom 29 (2.3%) developed PTLD. Results show that independent risk factors for PTLD after LT in adults were no Epstein-Barr virus load monitoring strategy, primary sclerosing cholangitis as an indication for LT, era (historic era linked to more intense long-term immunosuppression), and Epstein-Barr virus-seronegative recipient. No other independent risk factors were identified in this study. Of the 207 patients with primary sclerosing cholangitis as an indication for LT, 13 (6.3%) developed PTLD versus 16 out of 1074 (1.5%) patients with other underlying liver diseases (log-rank p <0.001). The yearly PTLD incidence was higher in the first year than in the later years after LT (2.4%/y vs. 0.6%/y) for primary sclerosing cholangitis, but not for other indications (0.16%/y). In Epstein-Barr virus-seronegative recipients PTLD occurred earlier after LT, while in 97% of seropositive recipients it could occur very late after LT.
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Affiliation(s)
- Bastian N Ruijter
- Department of Gastroenterology and Hepatology, LUMC Transplantation Center, Leiden University Medical Center, Leiden, The Netherlands
| | - Maarten E Tushuizen
- Department of Gastroenterology and Hepatology, LUMC Transplantation Center, Leiden University Medical Center, Leiden, The Netherlands
| | - Danny van der Helm
- Department of Gastroenterology and Hepatology, LUMC Transplantation Center, Leiden University Medical Center, Leiden, The Netherlands
- Department of Surgery, LUMC Transplantation Center, Leiden University Medical Center, Leiden, The Netherlands
| | - Mitchel Hew
- Department of Gastroenterology and Hepatology, LUMC Transplantation Center, Leiden University Medical Center, Leiden, The Netherlands
| | - Marjolein Reeven
- Department of Surgery, Division of HPB and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
- Department of Gastroenterology and Hepatology, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Ann C T M Vossen
- Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
| | - Herold J Metselaar
- Department of Gastroenterology and Hepatology, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Ian P J Alwayn
- Department of Surgery, LUMC Transplantation Center, Leiden University Medical Center, Leiden, The Netherlands
| | - Jeroen Dubbeld
- Department of Surgery, LUMC Transplantation Center, Leiden University Medical Center, Leiden, The Netherlands
| | - Wojciech G Polak
- Department of Surgery, Division of HPB and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Bart van Hoek
- Department of Gastroenterology and Hepatology, LUMC Transplantation Center, Leiden University Medical Center, Leiden, The Netherlands
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Vannas MJ, Åberg F, Nordin A, Tukiainen E, Savikko J, Isoniemi H. Comprehensive Complication Index to Monitor Morbidity and Mortality After Liver Transplantation in Primary Sclerosing Cholangitis. Ann Surg 2023; 278:e773-e779. [PMID: 36825495 PMCID: PMC10481909 DOI: 10.1097/sla.0000000000005831] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/25/2023]
Abstract
OBJECTIVE The objective of this study was to investigate the short-term and long-term morbidity after liver transplantation (LTx) in patients with primary sclerosing cholangitis (PSC). BACKGROUND PSC is a common indication for LTx in Scandinavia. Recently, research has focused on long-term survival and morbidity. The Comprehensive Complication Index (CCI) precisely describes postsurgical complications, by considering both number and severity. PATIENTS AND METHODS Two patient groups were compared: those with classical PSC symptoms (n=148) and those with increased risk of cholangiocarcinoma (n=51, premalignant group). Two CCI scores were calculated, at 1-year post-LTx and a cumulative overall score at the latest follow-up. In addition, we investigated factors potentially related to high CCI. RESULTS The 1-year median CCI were 29.6 and 26.2 in the classical and premalignant groups, respectively ( P =0.308). The median overall CCI were 43.2 and 46.8 ( P =0.765), respectively. Patient survival was significantly lower in patients with 1-year CCI>42. The most common complications associated with low survival were cholangitis, infections, and hypertension. One-year and overall CCI were similar between sexes and different types of biliary anastomosis. Patients with pre-LTx Model for End-stage Liver Disease scores >20 had higher 1-year and overall CCI (36.2 and 52.6, respectively) than those with lower Model for End-stage Liver Disease scores. Both low (<22) and high (>25 kg/m 2 ) body mass indices were associated with high overall 1-year and overall CCI (50.9 and 41.8, respectively), but median body mass indices were associated with significantly lower 1-year and overall CCI (38.4, P =0.023). CONCLUSIONS The previously determined 1-year CCI cutoff of 42 could significantly predict survival post-LTx. Mortality and morbidity were not significantly different between the PSC groups analyzed.
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Fuochi E, Anastasio L, Lynch EN, Campani C, Dragoni G, Milani S, Galli A, Innocenti T. Main factors influencing long-term outcomes of liver transplantation in 2022. World J Hepatol 2023; 15:321-352. [PMID: 37034235 PMCID: PMC10075010 DOI: 10.4254/wjh.v15.i3.321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/24/2022] [Accepted: 02/22/2023] [Indexed: 04/11/2023] Open
Abstract
Liver transplant (LT) outcomes have markedly improved in the recent decades, even if long-term morbidity and mortality are still considerable. Most of late deaths are independent from graft function and different comorbidities, including complications of metabolic syndrome and de novo neoplasms, seem to play a key role in determining long-term outcomes in LT recipients. This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term management and follow-up after liver transplantation. In particular, the reduction of drug toxicity, the use of tools to identify high-risk patients, and setting up a multidisciplinary team also for long-term management of LT recipients may further improve survival after liver transplantation.
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Affiliation(s)
- Elisa Fuochi
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Lorenzo Anastasio
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Erica Nicola Lynch
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
- Department of Medical Biotechnologies, University of Siena, Siena 53100, Italy
| | - Stefano Milani
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Andrea Galli
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Tommaso Innocenti
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
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Bourdeleau P, Larrey E, Allaire M, Charlotte F, Vaillant JC, Lebray P. "De novo" cholangiocarcinoma 20 years after liver transplantation for primary sclerosing cholangitis: Lifelong screening needed! Clin Res Hepatol Gastroenterol 2022; 46:101827. [PMID: 34740844 DOI: 10.1016/j.clinre.2021.101827] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 08/17/2021] [Accepted: 10/28/2021] [Indexed: 02/04/2023]
Abstract
We report a rare and very late case of de novo cholangiocarcinoma in a patient transplanted for primary sclerosing cholangitis. An exhaustive analysis of the literature and of our case highlight the very poor prognosis of this type of tumor due to the delay in diagnosis and the potential value of a six-monthly MRI surveillance as soon as cholangitis recurs, but also in the presence of chronic digestive inflammation, whatever the mechanism.
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Affiliation(s)
- Pauline Bourdeleau
- Médecine Sorbonne Université, Service d'Hépato-gastroentérologie, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, 47-83 Boulevard de l'Hôpital, Paris 75013, France
| | - Edouard Larrey
- Médecine Sorbonne Université, Service d'Hépato-gastroentérologie, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, 47-83 Boulevard de l'Hôpital, Paris 75013, France
| | - Manon Allaire
- Médecine Sorbonne Université, Service d'Hépato-gastroentérologie, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, 47-83 Boulevard de l'Hôpital, Paris 75013, France; Inserm U1149, Centre de Recherche sur l'Inflammation, France Faculté de Médecine Xavier Bichat, Université Paris Diderot, Paris, France
| | - Frederic Charlotte
- Médecine Sorbonne Université, Service d'anatomopathologie, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Paris, France
| | - Jean Christophe Vaillant
- Médecine Sorbonne Université, Service de Chirurgie Digestive et Hépato-Bilio-pancréatique - Transplantation Hépatique, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Paris, France
| | - Pascal Lebray
- Médecine Sorbonne Université, Service d'Hépato-gastroentérologie, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, 47-83 Boulevard de l'Hôpital, Paris 75013, France.
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8
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Moon HH, Shin DH, Choi YI. De Novo Intrahepatic Cholangiocarcinoma After Deceased Donor Liver Transplant in an Adult Patient. EXP CLIN TRANSPLANT 2022; 20:316-320. [PMID: 35352635 DOI: 10.6002/ect.2021.0437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Survival after liver transplant has progressively improved over recent decades. Recurrent or de novo malignancy, however, remains a major cause of patient death after transplant. Here, we have described a patient who developed de novo intrahepatic cholangiocarcinoma in the graft liver after orthotopic liver transplant. The 48-year-old male patient had end-stage liver disease from hepatitis B-related liver cirrhosis and a Model for End-Stage Liver Disease score of 26 and was listed for liver transplant. Recurrent esophageal variceal hemorrhage, severe ascites, and splenomegaly had complicated the liver disease. He underwent emergent whole organ, deceased donor liver transplant for liver cirrhosis. The donor liver was procured through the standard donation after brain death process from a 72-year-old man who died of intracranial hemorrhage. The graft weighted 1500 g and had normal color, and cold ischemia time was 5 hours upon arrival at our hospital. The patient's early postoperative course was uneventful. Two months posttransplant, the patient presented to the emergency department with fever, abdominal pain, and skin rash. Computed tomography revealed a focal biliary stricture in the right hepatic duct. Magnetic resonance cholangiopancreatography identified intrahepatic duct dilatations. Subsequent endoscopic retrograde cholangiography demonstrated marked intra- and extrahepatic biliary dilatation. We considered it to be a benign stricture and inserted plastic stents. He recovered from biliary stricture-related cholangitis. Approximately 10 months posttransplant, the patient was admitted with fever and skin rash. Marked dilatation of the intrahepatic bile duct was shown with a poorly enhancing tumor in the right lobe of the graft. Percutaneous transhepatic biliary drainage and tumor biopsy confirmed intrahepatic cholangiocarcinoma. We believe this to be the first case of de novo intrahepatic cholangiocarcinoma in a patient with hepatitis B-related end-stage liver disease after liver transplant without primary sclerosing cholangitis.
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Affiliation(s)
- Hyung Hwan Moon
- From the Department of Surgery, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Korea
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9
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Tokalioglu AA, Ozgun YM, Celik F, Akdogan M, Bostanci EB, Turan T, Turkmen O. High Grade Serous Ovarian Carcinoma in a Liver Transplant Recipient Patient: A Case Report and Review of Literature. Transplant Proc 2022; 54:153-157. [PMID: 34996597 DOI: 10.1016/j.transproceed.2021.12.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Accepted: 12/06/2021] [Indexed: 02/07/2023]
Abstract
According to GLOBOCAN 2020 data, the incidence of ovarian cancer is 1.6%. Ovarian cancer ranks 19th in incidence and 15th in mortality with a rate of 2.1%. High-grade serous ovarian cancer is the most common subtype of malignant ovarian tumors, and around 70% to 80% of all ovarian malignancies are included in this group. The incidence of gynecologic malignancies in liver transplant recipients is between 0% and 1.5%, and the duration of diagnosis for gynecologic cancer after transplantation is between 1 and 59 months. A 52-year-old patient was admitted to our hospital complaining of a periumbilical nodule. Her medical history revealed she had a cadaver liver transplantation in 2003 because of cirrhosis due to hepatitis B. On her physical examination, an erythematous nodular lesion was observed in the umbilical region. Ultrasonography demonstrated diffuse ascites and approximately 30 mm of a soft tissue density with lobulated contours located on the periumbilical skin. Both cytology and biopsy results were reported consistent with high-grade serous ovarian cancer. She underwent an operation, she had no problems during the postoperative follow-ups, and she was discharged on the eighth postoperative day. According to the 2018 International Federation of Gynecology and Obstetrics staging criteria for ovarian cancer, the patient's cancer was stage IVB. The patient received 6 cycles of adjuvant chemotherapy that included carboplatin (AUC = 6) and paclitaxel (175 mg/m2). The patient was evaluated as having a complete response according to Response Evaluation Criteria in Solid Tumors. The patient has been disease-free for 11 months after diagnosis.
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Affiliation(s)
- Abdurrahman Alp Tokalioglu
- Department of Gynecologic Oncology, Ankara City Hospital, University of Health Sciences, Ankara, Turkey.
| | - Yigit Mehmet Ozgun
- Department of Gastrointestinal Surgery, Ankara City Hospital, University of Health Sciences, Ankara, Turkey
| | - Fatih Celik
- Department of Gynecologic Oncology, Ankara City Hospital, University of Health Sciences, Ankara, Turkey
| | - Meral Akdogan
- Department of Gastroenterology, Ankara City Hospital, University of Health Sciences, Ankara, Turkey
| | - Erdal Birol Bostanci
- Department of Gastrointestinal Surgery, Ankara City Hospital, University of Health Sciences, Ankara, Turkey
| | - Taner Turan
- Department of Gynecologic Oncology, Ankara City Hospital, University of Health Sciences, Ankara, Turkey
| | - Osman Turkmen
- Department of Gynecologic Oncology, Ankara City Hospital, University of Health Sciences, Ankara, Turkey
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10
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Colmenero J, Tabrizian P, Bhangui P, Pinato DJ, Rodríguez-Perálvarez ML, Sapisochin G, Bhoori S, Pascual S, Senzolo M, Al-Adra D, Herrero JI, Petrowsky H, Dawson LA, Hosni A, Kutzke JL, Gastaca M, Watt KD. De Novo Malignancy After Liver Transplantation: Risk Assessment, Prevention, and Management-Guidelines From the ILTS-SETH Consensus Conference. Transplantation 2022; 106:e30-e45. [PMID: 34905760 DOI: 10.1097/tp.0000000000003998] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
De novo malignancies (DNMs) following liver transplantation (LT) have been reported as 1 of the major causes of late mortality, being the most common cause of death in the second decade after LT. The overall incidence of DNMs is reported to be in the range of 3.1% to 14.4%, and the incidence is 2- to 3-fold higher in transplant recipients than in age- and sex-matched healthy controls. Long-term immunosuppressive therapy, which is the key in maintaining host tolerance and achieving good long-term outcomes, is known to contribute to a higher risk of DNMs. However, the incidence and type of DNM also depends on different risk factors, including patient demographics, cause of the underlying chronic liver disease, behavior (smoking and alcohol abuse), and pre-existing premalignant conditions. The estimated standardized incidence ratio for different DNMs is also variable. The International Liver Transplantation Society-Spanish Society of Liver Transplantation Consensus Conference working group on DNM has summarized and discussed the current available literature on epidemiology, risk factors, management, and survival after DNMs. Recommendations for screening and surveillance for specific tumors, as well as immunosuppression and cancer-specific management in patients with DNM, are summarized.
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Affiliation(s)
- Jordi Colmenero
- Liver Transplantation, Liver Unit Hospital Clínic Barcelona, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
| | | | - Prashant Bhangui
- Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Delhi NCR, India
| | - David James Pinato
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom
| | - Manuel L Rodríguez-Perálvarez
- Department of Hepatology and Liver Transplantation, Hospital Universitario Reina Sofía, University of Córdoba, IMIBIC, CIBERehd, Córdoba, Spain
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, Toronto General Hospital, University of Toronto, ON, Canada
| | - Sherrie Bhoori
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Sonia Pascual
- Liver Unit, CIBERehd, ISABIAL, HGU Alicante, Alicante, Spain
| | - Marco Senzolo
- Multivisceral Transplant Unit, University Hospital of Padua, Padua, Italy
| | - David Al-Adra
- University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - J Ignacio Herrero
- Liver Unit, Clinica Universidad de Navarra, IdiSNA, CIBERehd, Pamplona, Spain
| | - Henrik Petrowsky
- Swiss HPB and Transplantation Center, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Laura A Dawson
- Princess Margaret Cancer Centre/University Health Network, University of Toronto, Toronto, ON, Canada
| | - Ali Hosni
- Princess Margaret Cancer Centre/University Health Network, University of Toronto, Toronto, ON, Canada
| | | | - Mikel Gastaca
- Cruces University Hospital, Biocruces Bizkaia Health Research Institute, University of the Basque Country, Bilbao, Spain
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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11
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Haider M, Bapatla A, Ismail R, Chaudhary AJ, Iqbal S, Haider SM. The Spectrum of Malignant Neoplasms among Liver Transplant Recipients: Sociodemographic Factors, Mortality, and Hospital Burden. Int J Med Sci 2022; 19:299-309. [PMID: 35165515 PMCID: PMC8795812 DOI: 10.7150/ijms.66533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 12/27/2021] [Indexed: 11/06/2022] Open
Abstract
Objective: To determine the nationwide prevalence of malignant neoplasms (excluding hepatocellular carcinoma-HCC) in hospitalized liver transplant recipients and to study the hospital utilization, and mortality to the incidence of malignancies. To the best of our knowledge, few epidemiological studies addressed outcomes in post-liver transplant patients, such as the annual number of hospitalizations, mortality, patient characteristics regarding malignancies. Methods: NIS database was queried between 2016 and 2018 to retrieve records of patients admitted with a principal or secondary diagnosis of liver transplant following the International Classification of Diseases, tenth Revision (ICD-10). The population was divided into case and control groups according to the presence and absence of malignant neoplasm (MN) except for HCC. We also compared the incidence of MN in LTX patients and non-LTX matched cohort. Results: A total of 7.28% admissions were associated with malignant neoplasms (except HCC) in LTX patients. Lymphomas, respiratory, gastrointestinal (excluding HCC), leukemia, and head/neck were commonest cancers with estimated admission rates of 0.97%, 0.90%, 0.80%, 0.53%, and 0.49%, respectively. Lung cancer was the most frequent malignant neoplasm among White and Black racial/ethnic groups (15.78% and 14.8%), whereas lymphoma was pervasive among Hispanics (20.3%). Lung cancer had the highest in-hospital mortality (10.55%), followed by the cancer of the nervous system (9.09%). The LTX and non-LTX cohort comparison showed that LTX patients are at increased risk of head and neck cancers, skin cancers, lymphomas, tumors, and Myelodysplastic syndrome. According to a multivariate analysis, a statistically significant association existed between malignant neoplasms in LTX patients and the following factors: increasing age (P < .001), higher mortality (P < .001), females with 29% lesser odds than males (P < .001), Black race and Hispanic ethnicity with 20% and 26% lesser odds as compared to White (P < .05). Clinical factors included smoking, Alcoholic cirrhosis, Hepatitis B, and Hepatitis C, were statistically significant risk factors of post-liver transplantation malignancies. Conclusions: Malignancies were frequent among elderly patients and predominantly in males. Lymphoproliferative diseases were the most prevalent malignancy types, followed by respiratory/lung cancer- which showed the highest mortality risk of all cancers. LTX patients are at increased risk of head and neck cancers, skin cancers, lymphoma, tumors, and Myelodysplastic syndrome compared to non-LTX patients.
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Affiliation(s)
- Maryam Haider
- Department of Internal Medicine, Detroit Medical Center/Wayne State University-Sinai Grace Hospital, Detroit, USA
| | - Anusha Bapatla
- Department of Internal Medicine, Detroit Medical Center/Wayne State University-Sinai Grace Hospital, Detroit, USA
| | - Rana Ismail
- Department of Internal Medicine, Detroit Medical Center/Wayne State University-Sinai Grace Hospital, Detroit, USA
| | - Ahmed J Chaudhary
- Department of Internal Medicine, Detroit Medical Center/Wayne State University-Sinai Grace Hospital, Detroit, USA
| | - Sana Iqbal
- Department of Internal Medicine, Detroit Medical Center/Wayne State University-Sinai Grace Hospital, Detroit, USA
| | - Syed M Haider
- Department of Internal Medicine, Detroit Medical Center/Wayne State University-Sinai Grace Hospital, Detroit, USA
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12
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Dumortier J, Besch C, Moga L, Coilly A, Conti F, Corpechot C, Del Bello A, Faitot F, Francoz C, Hilleret MN, Houssel-Debry P, Jezequel C, Lavayssière L, Neau-Cransac M, Erard-Poinsot D, de Lédinghen V, Bourlière M, Bureau C, Ganne-Carrié N. Non-invasive diagnosis and follow-up in liver transplantation. Clin Res Hepatol Gastroenterol 2022; 46:101774. [PMID: 34332131 DOI: 10.1016/j.clinre.2021.101774] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 07/23/2021] [Indexed: 02/04/2023]
Abstract
The field of liver transplantation directly or indirectly embodies all liver diseases, in addition to specific ones related to organ rejection (cellular and humoral). The recommended non-invasive methods for determining the indication for liver transplantation are the Model for End-stage Liver Disease score, and the alpha-foetoprotein score in case of hepatocellular carcinoma. Radiological methods are the cornerstones for the diagnosis of vascular and biliary complications after liver transplantation. The possible diseases of the liver graft after transplantation are multiple and often intertwined. Non-invasive diagnostic methods have been poorly evaluated in this context, apart from the recurrence of hepatitis C. Liver biopsy remains the gold standard for evaluating graft lesions in the majority of cases, especially graft rejection.
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Affiliation(s)
- Jérôme Dumortier
- Service d'hépato-gastroentérologie, Unité de transplantation hépatique, Hôpital Edouard Herriot - HCL, CHU Lyon, Lyon.
| | - Camille Besch
- Service de chirurgie hépato-bilio-pancréatique et transplantation hépatique, Hôpital Hautepierre, CHRU Strasbourg, Strasbourg
| | - Lucile Moga
- Service d'Hépatologie et Transplantation Hépatique, Hôpital Beaujon, APHP, Clichy
| | - Audrey Coilly
- Centre Hépato-Biliaire, Hôpital Paul Brousse, APHP, Villejuif
| | - Filomena Conti
- Service d'Hépatologie et Transplantation Hépatique, Hôpital de la Pitié Salpétrière, APHP, Paris
| | | | - Arnaud Del Bello
- Département de néphrologie et transplantation d'organes, Hôpital Rangueil, CHU Toulouse, Toulouse
| | - François Faitot
- Service de chirurgie hépato-bilio-pancréatique et transplantation hépatique, Hôpital Hautepierre, CHRU Strasbourg, Strasbourg
| | - Claire Francoz
- Service d'Hépatologie et Transplantation Hépatique, Hôpital Beaujon, APHP, Clichy
| | | | | | | | - Laurence Lavayssière
- Département de néphrologie et transplantation d'organes, Hôpital Rangueil, CHU Toulouse, Toulouse
| | | | - Domitille Erard-Poinsot
- Service d'hépato-gastroentérologie, Unité de transplantation hépatique, Hôpital Edouard Herriot - HCL, CHU Lyon, Lyon
| | - Victor de Lédinghen
- Unité Transplantation Hépatique, Hôpital Haut-Lévêque, CHU Bordeaux, Bordeaux
| | - Marc Bourlière
- Service d'hépato-gastroentérologie, Hôpital Saint Joseph & INSERM UMR 1252 IRD SESSTIM Aix Marseille Université, Marseille
| | | | - Nathalie Ganne-Carrié
- Service d'hépatologie, Hôpital Avicenne, APHP, Université Sorbonne Paris Nord, Bobigny & INSERM UMR 1138, Centre de Recherche des Cordeliers, Université de Paris
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13
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Mouchli M, Reddy S, Gerrard M, Boardman L, Rubio M. Usefulness of neutrophil-to-lymphocyte ratio (NLR) as a prognostic predictor after treatment of hepatocellular carcinoma." Review article. Ann Hepatol 2021; 22:100249. [PMID: 32896610 DOI: 10.1016/j.aohep.2020.08.067] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 08/07/2020] [Accepted: 08/08/2020] [Indexed: 02/06/2023]
Abstract
The neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker which has been investigated as a prognostic indicator in post-therapeutic recurrence and survival of patients with HCC. Our aim was to review all studies that assessed the prognostic value of pre-treatment NLR in predicting patient survival, cancer recurrence, and graft survival in patients undergoing various therapies for HCC. We searched the database of PubMed and Google Scholar to review all studies that have the word "NLR" and the word "HCC." We included all studies that assessed pre-treatment NLR as a prognostic factor in predicting outcomes in HCC patients. We excluded studies that assessed the correlation between post-treatment NLR or dynamic changes in NLR after treatment and HCC outcomes in an effort to minimize the confounding effect of each treatment on NLR. We reviewed 123 studies that studied the correlation between pre-treatment NLR and patient survival, 72 studies that evaluated the correlation between pre-treatment NLR and tumor recurrence, 21 studies that evaluated the correlation between NLR and tumor behavior, and 4 studies that assessed the correlation between NLR and graft survival. We found a remarkable heterogeneity between the methods of the studies, which is likely responsible for the differences in outcomes. The majority of the studies suggested a correlation between higher levels of pre-treatment NLR and poor outcomes. We concluded that NLR is a reliable and inexpensive biomarker and should be incorporated into other prognostic models to help determine outcomes following HCC treatment.
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Affiliation(s)
- Mohamad Mouchli
- Virginia Tech Carilion School of Medicine Department of Internal Medicine, Division of Gastroenterology & Hepatology, Roanoke, VA, United States; Virginia Tech Carilion School of Medicine Department of Internal Medicine, Roanoke, VA, United States; Mayo Clinic, Division of Gastroenterology & Hepatology, Rochester, MN, United States; Cleveland Clinic Foundation, Division of Gastroenterology & Hepatology, Cleveland, OH, United States.
| | - Shravani Reddy
- Virginia Tech Carilion School of Medicine Department of Internal Medicine, Roanoke, VA, United States
| | - Miranda Gerrard
- Virginia Tech Carilion School of Medicine, Roanoke, VA, United States
| | - Lisa Boardman
- Mayo Clinic, Division of Gastroenterology & Hepatology, Rochester, MN, United States
| | - Marrieth Rubio
- Virginia Tech Carilion School of Medicine Department of Internal Medicine, Division of Gastroenterology & Hepatology, Roanoke, VA, United States; Virginia Tech Carilion School of Medicine Department of Internal Medicine, Roanoke, VA, United States
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Saffioti F, Mavroeidis VK. Review of incidence and outcomes of treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis. World J Gastrointest Oncol 2021; 13:1336-1366. [PMID: 34721770 PMCID: PMC8529934 DOI: 10.4251/wjgo.v13.i10.1336] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 07/05/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a premalignant condition and a well-documented risk factor for cholangiocarcinoma (CCA) which is the most common malignancy in this setting and the leading cause of deaths in the recent years, with an increasing incidence. PSC-associated CCA has a geographical distribution that follows the incidence of PSC, with an observed ascending gradient from the Eastern to the Western and from the Southern to the Northern countries. It may arise at any location along the biliary tree but is most common in the perihilar area. Patients with PSC and intrahepatic or perihilar CCA are typically not suitable for liver resection, which is otherwise the treatment of choice with curative intent in patients with resectable tumours, providing a radical resection with clear margins can be achieved. This largely relates to the commonly advanced stage of liver disease at presentation, which allows consideration for liver resection only for a very limited number of suitable patients with PSC. On the other hand, remarkable progress has been reached in the last decades with the implementation of a protocol combining neoadjuvant chemoradiation and orthotopic liver transplantation (OLT) for the treatment of perihilar CCA, within specific criteria. Excellent results have been achieved particularly for PSC patients with this cancer, who seem to benefit the most from this treatment, having converted this into an accepted indication for transplantation and the standard of care in several experienced centres. Intrahepatic CCA as an indication for OLT remains controversial and has not been accepted given disappointing previous results. However, as recent studies have shown favourable outcomes in early intrahepatic CCA, it may be that under defined criteria, OLT may play a more prominent role in the future. Distal CCA in the context of PSC requires aggressive surgical treatment with curative intent, when feasible. This review provides insight about particular features of CCA in the setting of PSC, with a main focus on its incidence, considerations relating to its anatomical location and implications to treatment and outcomes, through the viewpoint of historical evolution of management, and future perspectives.
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Affiliation(s)
- Francesca Saffioti
- Department of Gastroenterology and Hepatology, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, Oxfordshire, United Kingdom
- UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital, University College London, London NW3 2QG, United Kingdom
| | - Vasileios K Mavroeidis
- Department of Surgery, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, United Kingdom
- Department of Transplant Surgery, North Bristol NHS Trust, Southmead Hospital, Bristol BS10 5NB, United Kingdom
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15
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Abstract
Background and aims Primary sclerosing cholangitis (PSC) is associated with an increased risk of hepatobiliary and colorectal cancer, but the risks of other cancer forms have not been explored. The aim of this study was to evaluate the risk of intestinal and extraintestinal cancers in a large, well-defined cohort of PSC patients. Material and method A matched cohort study of Swedish PSC patients was performed with up to ten comparators for each patient, matched for sex, age, and residency. The data were retrieved from national registers. Patients were followed from PSC diagnosis until cancer diagnosis, liver transplantation, first emigration date, death, or December 31, 2016. The risk of cancer was estimated using the Kaplan–Meier method and Cox regression models. Results In total, 1432 PSC patients with a verified diagnosis and 14,437 comparators were studied. The mean follow-up time was 15.9 years. Eighty-eight percent of the PSC patients had concomitant inflammatory bowel disease. PSC patients ran significantly increased risks of developing any cancer [HR 3.8, 95% confidence interval (CI) 3.3–4.3], hepatobiliary cancer (HR 120.9, 95% CI 72.0–203.1), colorectal cancer (HR 7.5, 95% CI 5.6–10.0), pancreatic cancer (HR 8.0, 95% CI 3.2–20.2), gastric cancer (HR 4.2, 95% CI 1.5–11.3), small bowel cancer (HR 21.1, 95% CI 3.5–128.2), and lymphoma (HR 3.0, 95% CI 1.6–5.7). PSC was not associated with a lower risk of any cancer form. Conclusions PSC patients have a four times overall increased risk of developing cancer compared to the general population, with increased risk of developing hepatobiliary, colorectal, and pancreatic cancer, as well as lymphoma. Supplementary Information The online version contains supplementary material available at 10.1007/s12072-021-10214-6.
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16
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Leung KK, Deeb M, Fischer SE, Gulamhusein A. Recurrent Primary Sclerosing Cholangitis: Current Understanding, Management, and Future Directions. Semin Liver Dis 2021; 41:409-420. [PMID: 34182588 DOI: 10.1055/s-0041-1730950] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Patients with primary sclerosing cholangitis (PSC) constitute 5 to 15% of patients listed for liver transplantation worldwide. Although post-transplant outcomes are favorable, recurrent PSC (rPSC) occurs in an important subset of patients, with higher prevalence rates reported with increasing time from transplant. Given its association with poor graft outcomes and risk of retransplant, effort has been made to understand rPSC, its pathophysiology, and risk factors. This review covers these facets of rPSC and focuses on implicated risk factors including pretransplant recipient characteristics, inflammatory bowel-disease-related factors, and donor-specific and transplant-specific factors. Confirming a diagnosis of rPSC requires thoughtful consideration of alternative etiologies so as to ensure confidence in diagnosis, management, subsequent risk assessment, and counseling for patients. Unfortunately, no cure exists for rPSC; however, future large-scale efforts are underway to better characterize the natural history of rPSC and its associated risk factors with hopes of identifying potential key targets for novel therapies.
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Affiliation(s)
- Kristel K Leung
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Maya Deeb
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Sandra E Fischer
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada
| | - Aliya Gulamhusein
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.,Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada
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17
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Nasser-Ghodsi N, Mara K, Watt KD. De Novo Colorectal and Pancreatic Cancer in Liver-Transplant Recipients: Identifying the Higher-Risk Populations. Hepatology 2021; 74:1003-1013. [PMID: 33544906 DOI: 10.1002/hep.31731] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 12/11/2020] [Accepted: 01/13/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIMS Gastrointestinal (GI) malignancies are common after liver transplantation. The aim of this study was to identify the risk and timing of the more common GI malignancies, colorectal and pancreatic cancer, to aid in optimizing potential posttransplant screening practices. APPROACH AND RESULTS Data from the United Network for Organ Sharing database of all adult liver-transplant recipients from 1997 to 2017 were analyzed and a comparison made with cancer incidence from general population data using Surveillance, Epidemiology, and End Results data. Of 866 de novo GI malignancies, 405 colorectal and 216 pancreas were identified. The highest cumulative incidence for colorectal cancer occurred in recipients with primary sclerosing cholangitis (PSC), recipients over the age of 50 with non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC)/cholangiocarcinoma (CCA), and females >50 years with alcohol-associated liver disease and HCC/CCA, with risk increasing above the general population within 5 years of transplant. Patients with PSC and HCC/CCA or NASH and HCC/CCA have the highest cumulative incidence of pancreatic cancer also rising within 5 years following transplant, with those patients >50 years old conferring the highest risk. CONCLUSIONS These data identify a high-risk cohort that warrants consideration for intensified individualized screening practices for colorectal cancer after liver transplantation. In addition to recipients with PSC, further study of recipients with NASH and HCC/CCA and females with alcohol-associated liver disease and HCC/CCA may be better tailored to colorectal cancer screening ideals. Higher-risk patient populations for pancreatic cancer (PSC and NASH with HCC/CCA) would benefit from further study to determine potential screening practices. GI malignancies occur at higher rates in liver-transplant patients compared with the general population. In the era of individualized medicine, this study identifies the highest-risk transplant recipients (PSC and NASH cirrhosis with coexisting HCC/CCA) who may benefit from altered screening practices for these malignancies.
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Affiliation(s)
| | - Kristin Mara
- Division of Biomedical Statistics and InformaticsMayo ClinicRochesterMN
| | - Kymberly D Watt
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMN
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18
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Altieri M, Sérée O, Lobbedez T, Segol P, Abergel A, Blaizot X, Boillot O, Boudjema K, Coilly A, Conti F, Chazouillères O, Debette-Gratien M, Dharancy S, Durand F, Duvoux C, Francoz C, Gugenheim J, Hardwigsen J, Houssel-Debry P, Kamar N, Latournerie M, Lebray P, Leroy V, Neau-Cransac M, Pageaux GP, Radenne S, Salamé E, Saliba F, Samuel D, Vanlemmens C, Besch C, Launoy G, Dumortier J. Risk factors of de novo malignancies after liver transplantation: a French national study on 11004 adult patients. Clin Res Hepatol Gastroenterol 2021; 45:101514. [PMID: 33714907 DOI: 10.1016/j.clinre.2020.07.019] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 07/13/2020] [Accepted: 07/13/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND After liver transplantation (LT),de novo malignancies are one of the leading causes of late mortality. The aim of the present retrospective study was to identify the risk factors of de novo malignancies in a large cohort of LT recipients in France, using Fine and Gray competing risks regression analysis. METHODS The study population consisted in 11004 adults transplanted between 2000 and 2013, who had no history of pre-transplant malignancy, except primary liver tumor. A Cox model adapted to the identification of prognostic factors (competitive risks) was used. RESULTS From the entire cohort, one (or more)de novo malignancy was reported in 1480 L T recipients (13.45%). The probability to develop a de novo malignancy after LT was 2.07% at 1 year, 13.30% at 5 years, and 28.01% at 10 years. Of the known reported malignancies, the most common malignancies were hematological malignancy (22.36%), non-melanoma skin cancer (19.53%) and lung cancer (12.36%). According to Fine and Gray competing risks regression multivariate analysis, were significant risk factors for post-LT de novo malignancy: recipient age (Subdistribution Hazard Ratio (SHR) = 1.03 95%CI 1.03-1.04), male gender (SHR = 1.45 95%CI 1.27-1.67), non-living donor (SHR = 1.67 95%CI 1.14-2.38), a first LT (SHR = 1.35 95%CI 1.09-1.69) and the type of initial liver disease (alcohol-related liver disease (SHR = 1.63 95%CI 1.22-2.17), primary sclerosing cholangitis (SHR = 1.98 95%CI 1.34-2.91), and primary liver tumor (SHR = 1.88 95%CI 1.41-2.54)). Initial immunosuppressive regimen had no significant impact. CONCLUSION The present study confirms that LT recipient characteristics are associated with the risk ofde novo malignancy and this underlines the need for personalized screening in order to improve survival.
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Affiliation(s)
- Mario Altieri
- Hôpital Côte de Nacre, Service d'Hépato-Gastroentérologie, Nutrition et Oncologie Digestive, Caen, France; UFR Santé Caen France: U1086 INSERM- "ANTICIPE", Caen, France
| | - Olivier Sérée
- Réseau Régional de Cancérologie OncoBasseNormandie, Caen, France
| | - Thierry Lobbedez
- Hôpital Côte de Nacre, Néphrologie, CUMR CAEN CEDEX, France, Normandie Université, Unicaen UFR de Médecine, RDPLF, Caen, France
| | - Philippe Segol
- Hôpital Côte de Nacre, Service de chirurgie digestive et générale, Caen, France
| | - Armand Abergel
- CHU Estaing, Médecine Digestive, Institut Pascal., UMR 6602 UCA CNRS SIGMA, Clermont-Ferrand, France
| | - Xavier Blaizot
- Réseau Régional de Cancérologie OncoBasseNormandie, Caen, France
| | - Olivier Boillot
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Unité de Transplantation Hépatique, et Université Claude Bernard Lyon 1, France
| | - Karim Boudjema
- Hôpital Universitaire de Pontchaillou, Service d'Hépatologie et Transplantation Hépatique, Rennes, France
| | - Audrey Coilly
- AP-HP, Hôpital Paul Brousse, Centre Hépato-Biliaire, INSERM, Unité 1193, Villejuif, France
| | - Filomena Conti
- APHP - Hôpital de la Pitié Salpétrière, Service d'Hépatologie et Transplantation Hépatique, Paris, France
| | - Olivier Chazouillères
- AP-HP, Hôpital Saint-Antoine, Service d'Hépatologie, INSERM UMR S 938, CDR Saint-Antoine, Centre de Référence « Maladies inflammatoire des voies biliaires et hépatite auto-immune », Filière FILFOIE, Université Paris 6, UMR_S 938, CDR Saint-Antoine, Paris, France
| | - Maryline Debette-Gratien
- CHU Limoges, Service d'hépato-Gastroentérologie,, INSERM, U850, Université Limoges, Limoges, France
| | | | - François Durand
- APHP, Hôpital Beaujon, Service d'Hépatologie et Transplantation Hépatique - Université Paris Diderot - INSERM U1149, Clichy, France
| | | | - Claire Francoz
- APHP, Hôpital Beaujon, Service d'Hépatologie et Transplantation Hépatique - Université Paris Diderot - INSERM U1149, Clichy, France
| | - Jean Gugenheim
- Hôpital Universitaire de Nice, Service de Chirurgie Digestive et de Transplantation Hépatique - Université de Nice-Sophia-Antipolis, Nice, France
| | - Jean Hardwigsen
- APHM, Hôpital La Timone, Service Chirurgie Générale et Transplantation Hépatique Marseille, France
| | - Pauline Houssel-Debry
- Hôpital Universitaire de Pontchaillou, Service d'Hépatologie et Transplantation Hépatique, Rennes, France
| | - Nassim Kamar
- CHU Rangueil, Département de Néphrologie et Transplantation d'Organes, Toulouse, France
| | - Marianne Latournerie
- CHU Dijon, Service d'Hépato-gastroentérologie et Oncologie Digestive, Inserm EPICAD LNC-UMR1231, Université de Bourgogne-Franche Comté, Dijon, France
| | - Pascal Lebray
- CHU Dijon, Service d'Hépato-gastroentérologie et Oncologie Digestive, Inserm EPICAD LNC-UMR1231, Université de Bourgogne-Franche Comté, Dijon, France
| | - Vincent Leroy
- CHU Grenoble-Alpes, Service d'hépato-gastroentérologie, La Tronche, France
| | - Martine Neau-Cransac
- CHU de Bordeaux, Hôpital Haut Lévêque, Service de Chirurgie Hépatobiliaire et de Transplantation Hépatique, Bordeaux, France
| | | | - Sylvie Radenne
- Hospices civils de Lyon, Hôpital de la Croix-Rousse, Service d'Hépato-Gastroentérologie, Lyon, France
| | - Ephrem Salamé
- CHU Tours, Hôpital Trousseau Service de chirurgie digestive, oncologique et endocrinienne, Transplantation hépatique, Tours, France
| | - Faouzi Saliba
- AP-HP, Hôpital Paul Brousse, Centre Hépato-Biliaire, INSERM, Unité 1193, Villejuif, France
| | - Didier Samuel
- AP-HP, Hôpital Paul Brousse, Centre Hépato-Biliaire, INSERM, Unité 1193, Villejuif, France
| | - Claire Vanlemmens
- Hôpital Jean Minjoz, Service d'Hépatologie et Soins Intensifs Digestifs, Besançon, France
| | - Camille Besch
- CHRU Hautepierre, Service de chirurgie hépato-bilio-pancréatique et transplantation hépatique, Strasbourg, France
| | - Guy Launoy
- UFR Santé Caen France: U1086 INSERM- "ANTICIPE", Caen, France
| | - Jérôme Dumortier
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Unité de Transplantation Hépatique, et Université Claude Bernard Lyon 1, France.
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Bertelli R, Prosperi E, Faccani E, Ansaloni L. Laparoscopic right colectomy for colon cancer after liver transplantation. J Minim Access Surg 2021; 17:268-270. [PMID: 33723188 PMCID: PMC8083739 DOI: 10.4103/jmas.jmas_134_20] [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] [Indexed: 11/06/2022] Open
Abstract
The incidence of colorectal cancer (CRC) after liver transplantation is 0.5%–4%. Laparoscopic surgery is the standard-of-care treatment, however it is rarely performed in patients who had previously undergone liver transplantation. Few reports exist regarding minimally invasive surgery in such context and none about laparoscopic right colectomy. We present the case of a 64-year-old female with a history of liver transplantation in 2001 and who developed a right-sided CRC. A laparoscopic right colectomy was successfully performed, and the post-operative course was uneventful. Given the known benefits, we believe that laparoscopic approach should be considered in such patients.
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Affiliation(s)
- Riccardo Bertelli
- Department of Surgery and Major Trauma, General and Emergency Surgery Unit, Maurizio Bufalini Hospital, Cesena, FC, Italy
| | - Enrico Prosperi
- Department of Surgery and Major Trauma, General and Emergency Surgery Unit, Maurizio Bufalini Hospital, Cesena, FC, Italy
| | - Enrico Faccani
- Department of Surgery and Major Trauma, General and Emergency Surgery Unit, Maurizio Bufalini Hospital, Cesena, FC, Italy
| | - Luca Ansaloni
- Department of Surgery and Major Trauma, General and Emergency Surgery Unit, Maurizio Bufalini Hospital, Cesena, FC, Italy
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20
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Song J, Li Y, Bowlus CL, Yang G, Leung PSC, Gershwin ME. Cholangiocarcinoma in Patients with Primary Sclerosing Cholangitis (PSC): a Comprehensive Review. Clin Rev Allergy Immunol 2020; 58:134-149. [PMID: 31463807 DOI: 10.1007/s12016-019-08764-7] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Cholangiocarcinoma (CCA) is the most common malignancy in patients with primary sclerosing cholangitis (PSC) and carries a high rate of mortality. Although the pathogenesis of CCA in PSC is largely unknown, inflammation-driven carcinogenesis concomitant with various genetic and epigenetic abnormalities are underlying factors. The majority of CCA cases develop from a dominant stricture (DS), which is defined as a stricture with a diameter < 1.5 mm in the common bile duct or < 1.0 mm in the hepatic duct. In PSC patients presenting with an abrupt aggravation of jaundice, pain, fatigue, pruritus, weight loss, or worsening liver biochemistries, CCA should be suspected and evaluated utilizing a variety of diagnostic modalities. However, early recognition of CCA in PSC remains a major challenge. Importantly, 30-50% of CCA in PSC patients are observed within the first year following the diagnosis of PSC followed by an annual incidence ranging from 0.5 to 1.5 per 100 persons, which is nearly 10 to 1000 times higher than that in the general population. Cumulative 5-year, 10-year, and lifetime incidences are 7%, 8-11%, and 9-20%, respectively. When PSC-associated CCA is diagnosed, most tumors are unresectable, and no effective medications are available. Given the poor therapeutic outcome, the surveillance and management of PSC patients who are at an increased risk of developing CCA are of importance. Such patients include older males with large-duct PSC and possibly concurrent ulcerative colitis. Thus, more attention should be paid to patients with these clinical features, in particular within the first year after PSC diagnosis. In contrast, CCA is less frequently observed in pediatric or female PSC patients or in those with small-duct PSC or concurrent Crohn's disease. Recently, new biomarkers such as antibodies to glycoprotein 2 have been found to be associated with an increased risk of developing CCA in PSC. Herein, we review the literature on the pathogenesis, incidence, clinical features, and risk factors, with a focus on various diagnostic modalities of PSC-associated CCA.
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Affiliation(s)
- Junmin Song
- Department of Gastroenterology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, People's Republic of China.,Division of Rheumatology, Allergy and Clinical Immunology, University of California, 451 Health Science Drive, Suite 6510, Davis, CA, 95616, USA
| | - Yang Li
- Department of Intensive Care Unit (ICU), Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning, 110004, People's Republic of China
| | - Christopher L Bowlus
- Division of Gastroenterology and Hepatology, University of California, 451 Health Sciences Drive, Suite 6510, Davis, CA, 95616, USA
| | - GuoXiang Yang
- Division of Rheumatology, Allergy and Clinical Immunology, University of California, 451 Health Science Drive, Suite 6510, Davis, CA, 95616, USA
| | - Patrick S C Leung
- Division of Rheumatology, Allergy and Clinical Immunology, University of California, 451 Health Science Drive, Suite 6510, Davis, CA, 95616, USA.
| | - M Eric Gershwin
- Division of Rheumatology, Allergy and Clinical Immunology, University of California, 451 Health Science Drive, Suite 6510, Davis, CA, 95616, USA.
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21
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Over-diagnosed prostate cancer in solid organ recipients: lessons from the last 3 decades. Int Urol Nephrol 2020; 53:241-248. [PMID: 32926314 DOI: 10.1007/s11255-020-02636-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 09/03/2020] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Prostate cancer (PC) is the most common neoplasia in men. With aging of solid organ transplant recipients (SOTR), its incidence is likely to increase. The aim of this study was to analyze PC screening results retrospectively in renal transplant recipients (RTR), hepatic transplant recipients (HTR) and cardiac transplant recipients (CTR). PATIENTS AND METHODS A retrospective monocentric study of PC diagnosed in renal, hepatic or cardiac transplanted patients since 1989 was performed. All the patients were followed annually by digital rectal examination and prostate serum antigen (PSA) dosage. RESULTS 57 PC were diagnosed in 1565 SOTR male patients (3.6%): 35 RTR, 15 HTR, and 7 CTR. Standard incidence ratio (SIR) was 41.9. Mean age at the time of diagnosis was 64.5 (60.5-69.2). Mean time between transplantation and PC diagnosis was 95.7 (39.0-139.5) months. Median PSA rate was 7.0 (6.2-13) ng/mL. Clinical stages were T1, T2, and T3, respectively, for 29, 22 and 6 patients. Diagnosis was done by screening in 52 patients, after prostatitis in 1 and bone pain in another. Three PC were discovered on prostate chips after transurethral resection. Two patients were treated by active surveillance. 39 (68%) patients (25 RTR, 11 HTR and 3 CTR) were treated by radical prostatectomy. Histological results were 30 pT2 and 9 pT3 tumors, with 7 positive surgical margins. Gleason score was 5, 6, 7, 8 and 9 in, respectively, in 2, 24, 11, 1 and 1 patients. One patient with positive pelvic nodes was treated with hormonal therapy (HT). One had a biochemical relapse at 10 months and underwent salvage radiotherapy. Median follow-up was 85.2 months (46.1-115.0). 23 (40.4%) patients died. Two (3.6%) RTR and 1 (1.8%) CTR died from their PC. Standard incidence ratio were, respectively, 42.4, 48.2 and 39 in RTR, HTR and CTR. CONCLUSION Systematic screening in male SOTR after 50 years old could not be recommended. In the last 3 decades, we diagnosed too many low-risk prostate cancers strongly increasing the SIR but failing to decrease prostate cancer related mortality. SOTR should undergo individual screening with prior MRI when PSA rates are high. Management should not be different from that of the general population.
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Oliveira RC, Tavares-Silva E, Abrantes AM, Antunes H, Teixeira P, Gomes A, Martins R, Furtado E, Figueiredo A, Costa B, Cipriano MA, Tralhão JG, Botelho MF. De novo colorectal cancer after liver and kidney transplantation–Microenvironment disturbance. TRANSPLANTATION REPORTS 2020. [DOI: 10.1016/j.tpr.2020.100057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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23
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Sun JH, Hou JP, Kang YZ. Clinical significance of expression of PPP1R105 in hepatocellular carcinoma. Shijie Huaren Xiaohua Zazhi 2020; 28:765-776. [DOI: 10.11569/wcjd.v28.i16.765] [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] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a common malignant tumor with a poor prognosis. In this study, we evaluated the expression of the PPP1R105 gene in HCC and its relationship with prognosis through bioinformatics analysis. Then, we used immunohistochemistry to verify the expression of PPP1R105 protein.
AIM To investigate the expression of PPP1R105 (Ki-67 or MKI67) in HCC and its clinical significance.
METHODS The relative expression data of the PPP1R105 gene in various tumor tissues were retrieved from the tumor protein database and TCGA database and compared between cancer and paired normal tissues. The protein-protein interaction network (PPI) of PPP1R105 was constructed by using the STRING database. The progression free survival (DFS) and overall survival (OS) between the high and low PPP1R105 expression groups were compared. Eighty-one HCC patients who underwent surgery were retrospectively included in the study, and PPP1R105 protein expression was detected by immunohistochemistry. The relationship between PPP1R105 protein expression and patients' features was evaluated.
RESULTS The expression levels of PPP1R105 mRNA in different tumors were not significantly different. In HCC, the expression level of PPP1R105 mRNA was significantly higher than that of normal liver tissue, and the expression level was related with clinical stage. The aggregation index of PPI was 0.99, and the enrichment of protein interaction network was significant (P < 0.01). PPP1R105 was mainly enriched in cell cycle, cell aging, virus carcinogenesis, and p53 signaling pathway. The positive correlation between KIF18B and PPP1R105 was the most significant (rperson = 0.91, P < 0.05), while the negative correlation between MCELL and PPP1R105 was the most significant (rperson = -0.59, P < 0.05). DFS (HR = 1.90, P < 0.01) and OS (HR = 1.90, P < 0.01) in the high PPP1R105 expression group were significantly shorter than those in the low expression group. PPP1R105 protein was mainly expressed in the cytoplasm and nucleolus of the cells. Of the included 81 patients, 30 (37.0%) showed high expression of PPP1R105 protein. The proportion of patients with high expression of PPP1R105 protein was higher than that of patients with low expression of MIK67 protein (P < 0.05).
CONCLUSION PPP1R105 is highly expressed in patients with HCC, which is related to a poor DFS and OS. PPP1R105 can be used as a poor prognostic molecular marker in HCC.
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Affiliation(s)
- Jian-He Sun
- Department of Hepatobiliary Surgery, People's Hospital of Baodi District, Tianjin 301800, China
| | - Ji-Ping Hou
- Department of Hepatobiliary Surgery, People's Hospital of Baodi District, Tianjin 301800, China
| | - Yong-Zhen Kang
- Department of Hepatobiliary Surgery, People's Hospital of Baodi District, Tianjin 301800, China
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24
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Zen Y, Srinivasan P, Kitagawa M, Suzuki K, Heneghan M, Prachalias A. De novo perihilar cholangiocarcinoma arising in the allograft liver 15 years post-transplantation for biliary atresia. Pathol Int 2020; 70:563-567. [PMID: 32350971 DOI: 10.1111/pin.12944] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 04/08/2020] [Accepted: 04/13/2020] [Indexed: 12/23/2022]
Abstract
Most primary liver cancers diagnosed in allograft livers are recurrent tumors of the native liver origin, while donor-derived primary liver cancers are markedly less common. A 21-year-old woman who had liver transplantation for post-Kasai biliary atresia was recently referred for post-transplant biliary stricture. Her transplantation was performed at the age of 6 years using the whole liver graft from a 10-year-old donor and choledocho-jejunostomy. The post-transplant course was uneventful in the first 15 years until she presented with obstructive jaundice. The stricture was located at the level of the hepaticojejunostomy, and required percutaneous transhepatic drainage and bile duct dilatation. She underwent an exploratory laparotomy, which suggested a neoplastic process widely involving the extrahepatic and intrahepatic large bile ducts. The histological examination of the resected extrahepatic bile duct confirmed infiltrating moderately differentiated adenocarcinoma. Molecular tests of multiple short tandem repeat loci confirmed the donor origin of the tumor. After four cycles of chemotherapy with gemicitabine and cisplatin, she is currently on radiotherapy in view of potential re-transplantation. De novo, post-transplant cholangiocarcinoma of graft origin is extremely uncommon with only three other cases reported. Two were associated with recurrent primary sclerosing cholangitis, and all had choledocho-jejunostomy at the time of transplantation.
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Affiliation(s)
- Yoh Zen
- Institute of Liver Studies, King's College Hospital, London, UK
| | | | - Misa Kitagawa
- Department of Legal Medicine, Osaka Medical College, Osaka, Japan
| | - Koichi Suzuki
- Department of Legal Medicine, Osaka Medical College, Osaka, Japan
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25
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Abstract
PURPOSE OF REVIEW Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by progressive fibroinflammatory destruction of the intrahepatic and/or extrahepatic bile ducts. It is associated with a significantly increased risk of malignancy, particularly cholangiocarcinoma (CCA). In this review, we discuss what is currently known about the epidemiology of and risk factors for CCA in PSC as well as recent advances in its prevention, diagnosis, and surveillance. RECENT FINDINGS An area of major focus has been finding novel biomarkers (in serum, bile, and urine) for CCA. With the advancement of computing power, metabolomic and proteomic approaches, among other methods, may provide enhanced capability for differentiating between benign and malignant bile duct disease. Another area of focus has been the approach to CCA surveillance in PSC; a recent study has found that CCA surveillance in patients with PSC is associated with improved outcomes, including increased survival, thus advocating for its importance. SUMMARY Despite ongoing advancements in the study of PSC-associated CCA, early diagnosis of CCA remains difficult, treatment options are limited, and prognosis is often consequently poor. Continued research in the development of high-accuracy diagnostic tools, novel biomarkers, and surveillance techniques may help to increase the likelihood of diagnosing CCA at earlier stages, when therapeutic options have the highest likelihood of resulting in cure.
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Affiliation(s)
- Brian M Fung
- UCLA-Olive View Internal Medicine Residency Program
| | - James H Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, California, USA
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26
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O'Neill JP, Sexton DJ, O'Leary E, O'Kelly P, Murray S, Deady S, Daly F, Williams Y, Dean B, Fitzgerald C, Murad A, Mansoor N, O'Neill JO, Egan J, Houlihan DD, McCormick PA, Morris PG, Ni Raghallaigh S, Little D, Moloney FJ, Conlon PJ. Post-transplant malignancy in solid organ transplant recipients in Ireland, The Irish Transplant Cancer Group. Clin Transplant 2019; 33:e13669. [PMID: 31310037 DOI: 10.1111/ctr.13669] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Revised: 06/09/2019] [Accepted: 06/26/2019] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Solid organ transplant recipients are at increased risk of cancer compared to the general population. To date, this risk in Ireland has not been investigated. We conducted a national registry study of cancer incidence following solid organ transplantation. METHODS National centers for solid organ transplantation supplied their respective registry databases to cross-reference with episodes of malignancy from the National Cancer Registry Ireland (NCRI) between 1994 and 2014. Standardized incidence of cancer post-transplant was compared to the general population by means of standardized incidence ratios (SIRs), and between solid organ transplant types by incidence rate ratios. RESULTS A total of 3346 solid organ transplant recipients were included in this study. Kidney transplant recipients constituted the majority of participants (71.2%), followed by liver (16.8%), heart (6.4%), and lung (5.6%) transplants. The most common cancers within the composite of all transplant recipients included the following (SIR [95% CI]): squamous and basal cell carcinoma (20.05 [17.97, 22.31] and 7.16 [6.43, 7.96], respectively), non-Hodgkin lymphoma (6.23 [4.26, 8.59]), and renal cell carcinoma (3.36 [1.96, 5.38]). CONCLUSIONS This study reports the incidence of cancer following solid organ transplantation in Ireland. These results have significant national policy implications for surveillance, and early diagnosis in this patient group.
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Affiliation(s)
- James Paul O'Neill
- Department of Otolaryngology, Head and Neck Surgery, Beaumont Hospital & The Royal College of Surgeons in Ireland, Dublin, Ireland.,Royal College of Surgeons Ireland, Dublin, Ireland
| | - Donal J Sexton
- Department of Transplant Urology and Nephrology, National Kidney Transplant Service, Beaumont Hospital Dublin, Dublin, Ireland
| | | | - Patrick O'Kelly
- Department of Transplant Urology and Nephrology, National Kidney Transplant Service, Beaumont Hospital Dublin, Dublin, Ireland
| | - Susan Murray
- Department of Transplant Urology and Nephrology, National Kidney Transplant Service, Beaumont Hospital Dublin, Dublin, Ireland
| | | | - Fergus Daly
- Department of Transplant Urology and Nephrology, National Kidney Transplant Service, Beaumont Hospital Dublin, Dublin, Ireland
| | - Yvonne Williams
- Department of Transplant Urology and Nephrology, National Kidney Transplant Service, Beaumont Hospital Dublin, Dublin, Ireland
| | - Ben Dean
- Department of Transplant Urology and Nephrology, National Kidney Transplant Service, Beaumont Hospital Dublin, Dublin, Ireland
| | - Conall Fitzgerald
- Department of Otolaryngology, Head and Neck Surgery, Beaumont Hospital & The Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Aizuri Murad
- Department of Dermatology, School of Medicine, Mater Misericordiae University Hospital, University College Dublin, Dublin, Ireland
| | - Nazish Mansoor
- Department of Dermatology, School of Medicine, Mater Misericordiae University Hospital, University College Dublin, Dublin, Ireland
| | - Jim O O'Neill
- National Heart Transplant Center, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Jim Egan
- National Lung Transplantation Center, Mater University Hospital Dublin, Dublin, Ireland
| | - Diarmaid D Houlihan
- National Liver Transplant Center, St Vincent's University Hospital, Dublin, Ireland
| | - P Aiden McCormick
- National Liver Transplant Center, St Vincent's University Hospital, Dublin, Ireland
| | - Patrick G Morris
- Royal College of Surgeons Ireland, Dublin, Ireland.,Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland
| | | | - Dilly Little
- Department of Transplant Urology and Nephrology, National Kidney Transplant Service, Beaumont Hospital Dublin, Dublin, Ireland
| | - Fergal J Moloney
- Department of Dermatology, School of Medicine, Mater Misericordiae University Hospital, University College Dublin, Dublin, Ireland
| | - Peter J Conlon
- Royal College of Surgeons Ireland, Dublin, Ireland.,Department of Transplant Urology and Nephrology, National Kidney Transplant Service, Beaumont Hospital Dublin, Dublin, Ireland
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27
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Manzia TM, Angelico R, Gazia C, Lenci I, Milana M, Ademoyero OT, Pedini D, Toti L, Spada M, Tisone G, Baiocchi L. De novo malignancies after liver transplantation: The effect of immunosuppression-personal data and review of literature. World J Gastroenterol 2019; 25:5356-5375. [PMID: 31558879 PMCID: PMC6761240 DOI: 10.3748/wjg.v25.i35.5356] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Revised: 08/08/2019] [Accepted: 08/24/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Immunosuppression has undoubtedly raised the overall positive outcomes in the post-operative management of solid organ transplantation. However, long-term exposure to immunosuppression is associated with critical systemic morbidities. De novo malignancies following orthotopic liver transplants (OLTs) are a serious threat in pediatric and adult transplant individuals. Data from different experiences were reported and compared to assess the connection between immunosuppression and de novo malignancies in liver transplant patients. AIM To study the role of immunosuppression on the incidence of de novo malignancies in liver transplant recipients. METHODS A systematic literature examination about de novo malignancies and immunosuppression weaning in adult and pediatric OLT recipients was described in the present review. Worldwide data were collected from highly qualified institutions performing OLTs. Patient follow-up, immunosuppression discontinuation and incidence of de novo malignancies were reported. Likewise, the review assesses the differences in adult and pediatric recipients by describing the adopted immunosuppression regimens and the different type of diagnosed solid and blood malignancy. RESULTS Emerging evidence suggests that the liver is an immunologically privileged organ able to support immunosuppression discontinuation in carefully selected recipients. Malignancies are often detected in liver transplant patients undergoing daily immunosuppression regimens. Post-transplant lymphoproliferative diseases and skin tumors are the most detected de novo malignancies in the pediatric and adult OLT population, respectively. To date, immunosuppression withdrawal has been achieved in up to 40% and 60% of well-selected adult and pediatric recipients, respectively. In both populations, a clear benefit of immunosuppression weaning protocols on de novo malignancies is difficult to ascertain because data have not been specified in most of the clinical experiences. CONCLUSION The selected populations of tolerant pediatric and adult liver transplant recipients greatly benefit from immunosuppression weaning. There is still no strong clinical evidence on the usefulness of immunosuppression withdrawal in OLT recipients on malignancies. An interesting focus is represented by the complete reconstitution of the immunological pathways that could help in decreasing the incidence of de novo malignancies and may also help in treating liver transplant patients suffering from cancer.
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Affiliation(s)
- Tommaso Maria Manzia
- HPB and Transplant Unit, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | - Roberta Angelico
- Division of Abdominal Transplantation and HPB Surgery, Bambino Gesù Children's Hospital IRCCS, Rome 00165, Italy
| | - Carlo Gazia
- HPB and Transplant Unit, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
- Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC 27101, United States
| | - Ilaria Lenci
- Hepatology and Liver Transplant Unit, University of Tor Vergata, Rome 00133, Italy
| | - Martina Milana
- Hepatology and Liver Transplant Unit, University of Tor Vergata, Rome 00133, Italy
| | | | - Domiziana Pedini
- Division of Abdominal Transplantation and HPB Surgery, Bambino Gesù Children's Hospital IRCCS, Rome 00165, Italy
| | - Luca Toti
- HPB and Transplant Unit, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | - Marco Spada
- Division of Abdominal Transplantation and HPB Surgery, Bambino Gesù Children's Hospital IRCCS, Rome 00165, Italy
| | - Giuseppe Tisone
- HPB and Transplant Unit, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | - Leonardo Baiocchi
- Hepatology and Liver Transplant Unit, University of Tor Vergata, Rome 00133, Italy
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Abstract
PURPOSE OF REVIEW Posttransplant lymphoproliferative disorder (PTLD), frequently associated with Epstein-Barr virus (EBV), is one of the most serious complications leading to worse patient and graft outcomes. Hence, we summarize in this review relevant studies published about PTLD in the last 18 months. RECENT FINDINGS Recent studies have improved the knowledge about epidemiology, prophylaxis, diagnosis and PTLD treatment. Special interest has developed in improving the last PTLD classification of the World Health Organization, increasing the accuracy of diagnostic tests for EBV viral load quantification and discriminating the genetic differences between PTLD types. There seems to be no real advantage in the use of antiviral drugs for prophylaxis, but better results in therapeutic approaches are being obtained mainly with the use of rituximab with or without chemotherapy, but also with the possibility of using adoptive T-cell therapy or new drugs. SUMMARY PTLD continues being a complication that requires continued effort of the scientific community to reduce its incidence and to develop better diagnostic tests and new strategies that improve results in prophylaxis and treatment.
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Long-term care of transplant recipients: de novo neoplasms after liver transplantation. Curr Opin Organ Transplant 2019; 23:187-195. [PMID: 29324517 DOI: 10.1097/mot.0000000000000499] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE OF REVIEW Since the first liver transplantation in the early 1960s, there have been significant improvements in the recipients' long-term outcome. Patients who have undergone transplantation are exposed to a high risk of developing neoplastic disease, not only because of their chronic immunosuppression, but also related to physiological aging, lifestyle, chronic viral infections, liver disease cause, and carcinogenic immunosuppressants. The present review covers the latest and most relevant data on de novo neoplasms after liver transplantation, and discusses their implications for clinical practice. RECENT FINDINGS Given the impact of de novo neoplasms, in terms of morbidity and mortality, transplant teams must be prepared to diagnose and treat these conditions promptly. Dedicated cancer screening protocols are warranted. Although surveillance strategies are based on data concerning the general population, they should be customized in the light of each transplant recipient's risk factors. The resulting risk stratification is crucially important to the design of early intervention programs, and for addressing the modulation of individualized immunosuppressive regimens. SUMMARY De novo malignancies are a significant issue for the liver transplant population, but targeted screening programs have shown that survival rates similar to those of nonimmunosuppressed patients can be achieved. New oncological surveillance strategies covering the prophylaxis, monitoring, and treatment of de novo neoplasms should take high priority in clinical research.
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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: 17] [Impact Index Per Article: 2.8] [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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Fung BM, Lindor KD, Tabibian JH. Cancer risk in primary sclerosing cholangitis: Epidemiology, prevention, and surveillance strategies. World J Gastroenterol 2019; 25:659-671. [PMID: 30783370 PMCID: PMC6378537 DOI: 10.3748/wjg.v25.i6.659] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 01/10/2019] [Accepted: 01/14/2019] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by progressive fibroinflammatory destruction of the intra- and/or extrahepatic biliary ducts. While its features and disease course can be variable, most patients with PSC have concurrent inflammatory bowel disease and will eventually develop liver cirrhosis and end-stage liver disease, with liver transplantation representing the only potentially curative option. Importantly, PSC is associated with a significantly increased risk of malignancy compared to the general population, mainly cholangiocarcinoma, gallbladder carcinoma, hepatocellular carcinoma, and colorectal cancer, with nearly 50% of deaths in patients with PSC being due to cancer. Therefore, robust surveillance strategies are needed, though uncertainty remains regarding how to best do so. In this review, we discuss the epidemiology, prevention, and surveillance of cancers in patients with PSC. Where evidence is limited, we present pragmatic approaches based on currently available data and expert opinion.
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Affiliation(s)
- Brian M Fung
- UCLA-Olive View Internal Medicine Residency Program, Olive View-UCLA Medical Center, Sylmar, CA 91342, United States
| | - Keith D Lindor
- Office of the University Provost, Arizona State University, Phoenix, AZ 85004, United States
| | - James H Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA 91342, United States
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Mouchli MA, Singh S, Boardman L, Bruining DH, Lightner AL, Rosen CB, Heimbach JK, Hasan B, Poterucha JJ, Watt KD, Kane SV, Raffals LE, Loftus EV. Natural History of Established and De Novo Inflammatory Bowel Disease After Liver Transplantation for Primary Sclerosing Cholangitis. Inflamm Bowel Dis 2018; 24. [PMID: 29522202 PMCID: PMC6085995 DOI: 10.1093/ibd/izx096] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND The course of inflammatory bowel disease (IBD) after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is poorly understood. We describe the natural history of established IBD after LT (including risk of disease progression, colectomy, and neoplasia) and de novo IBD. METHODS In a retrospective cohort, we identified all patients with PSC who underwent LT for advanced PSC at Mayo Clinic, Rochester, Minnesota. Risk factors were identified using multivariate Cox proportional hazard analysis. RESULTS Three hundred seventy-three patients were identified (mean age, 47.5 ± 11.7 years; 64.9% male). Over a median (range) of 10 (5.5-17.1) years, 151 patients with PSC-IBD with an intact colon at the time of LT were studied. Post-LT, despite transplant-related immunosuppression, 56/151 (37.1%) required escalation of therapy, whereas 87 had a stable course (57.6%) and 8 patients (5.3%) improved. The 1-, 5-, and 10-year risks of progression of IBD were 4.0%, 18.5%, and 25.5%, respectively. On multivariate analysis, tacrolimus-based immunosuppression post-LT were associated with unfavorable course, and azathioprine use after LT was associated with improved course post-LT. Of 84 patients with no evidence of IBD at the time of LT, 22 (26.2%) developed de novo IBD post-LT. The 1-, 5-, and 10-year cumulative incidences of de novo IBD were 5.5%, 20.0%, and 25.4%, respectively. On univariate analysis, mycophenolate mofetil use after LT was associated with increased risk of de novo IBD, but azathioprine use after LT seemed to be protective. CONCLUSIONS The 10-year cumulative probability of IBD flare requiring escalation of therapy after LT for PSC was 25.5%, despite immunosuppression for LT. The 10-year cumulative risk of de novo IBD after LT for PSC was 25.4%. Transplant-related immunosuppression may modify the risk of de novo IBD, with an increased risk with mycophenolate and a decreased risk with azathioprine. 10.1093/ibd/izx096_video1izx096.video15746673864001.
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Affiliation(s)
- Mohamad A Mouchli
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota,Division of Gastroenterology and Hepatology, Carilion Clinic, Roanoke, Virginia
| | - Siddharth Singh
- Division of Gastroenterology, Department of Internal Medicine, UCSD, La Jolla, California
| | - Lisa Boardman
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - David H Bruining
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Amy L Lightner
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota
| | - Charles B Rosen
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota,William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota
| | - Julie K Heimbach
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota
| | - Bashar Hasan
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - John J Poterucha
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Sunanda V Kane
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Laura E Raffals
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota,Address correspondence to: Edward V. Loftus, Jr., MD, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905 ()
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