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Xu X, Zhang S, Luo Z, Zheng Y, Kong T, Huang C, Qiu Z. Frontiers and Controversies in De Novo Gastrointestinal Tumors After Organ Transplantation: Current Progress and Future Directions. Ann Surg Oncol 2025; 32:3392-3405. [PMID: 40035907 DOI: 10.1245/s10434-025-16975-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 01/21/2025] [Indexed: 03/06/2025]
Abstract
The increasing success of organ transplantation has significantly improved survival for patients with end-stage diseases, yet it introduces a complex dilemma: the elevated risk for the development of de novo gastrointestinal (GI) tumors. The sustained immunosuppression required to maintain graft function paradoxically undermines the body's natural defenses against cancer, leading to a higher incidence, aggressive progression, and atypical presentations of GI tumors among transplant recipients compared with the general population. This presents a pressing challenge: balancing the dual imperatives of preventing graft rejection and effectively managing malignancies. Current treatment paradigms, including surgical approaches, chemotherapy, radiation therapy, and the emerging role of immunotherapy, are fraught with complexities due to the altered immune landscape in these patients. This review underscores the critical need to understand the multifaceted relationship between post-transplantation immunosuppression and tumorigenesis, providing a comprehensive exploration of epidemiologic shifts, pathophysiologic insights, and the intricacies of the tumor microenvironment in this unique patient population. Understanding and managing GI tumors in transplant recipients is not only a clinical challenge, but also a necessary frontier in transplant oncology, promising to refine therapeutic strategies and improve the longevity and quality of life for this growing patient cohort.
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Affiliation(s)
- Ximo Xu
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shaopeng Zhang
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zai Luo
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yan Zheng
- Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tingting Kong
- Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chen Huang
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Zhengjun Qiu
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Al-Qudimat AR, Al Darwish MB, Altahtamouni SB, Singh K, Al-Zoubi RM, Aboumarzouk OM, Al-Ansari A. Chronic kidney diseases and the risk of colorectal cancer: A systematic review and meta-analysis. Arab J Urol 2023; 21:258-266. [PMID: 38178950 PMCID: PMC10763595 DOI: 10.1080/2090598x.2023.2225315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 06/11/2023] [Indexed: 01/06/2024] Open
Abstract
Objective We conducted this review to offer a comprehensive search and up-to-date overview of the currently available information about the probability risk of colorectal cancer among chronic kidney disease patients. Method We performed a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews (PRISMA) and meta-analysis guidelines. We identified, reviewed, and extracted from Scopus, PubMed, EMBASE, and Komaki Databases for research publications on chronic kidney disease and colorectal cancer published between February 2016 and January 2023. We meta-analyzed the prevalence of colorectal cancer with chronic kidney disease. We ran a random effect meta-regression. Risk-of-bias assessment was evaluated using the Newcastle-Ottawa Scale. The systematic review was registered with PROSPERO (CRD42023400983). Results The risk of CRC in chronic kidney diseases was reported in 50 research studies, which included 4,337,966 people from 16 different countries. SIR of CRC was obtained from 14 studies and showed a significant relationship between CRC with CKD patients, with a pooled SIR of 1.33; 95% CI (1.30-1.36), with higher heterogeneity (Q = 121.82, P < 0.001, and I2 = 86.9%). Metaregression showed that there was no significant correlation between the risk of CRC and the proportion of males or age. Conclusion Overall, this study shows that patients with chronic kidney disease have a significantly increased risk of colorectal cancer. More studies with larger sample sizes, and robust surveillance are needed.
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Affiliation(s)
- Ahmad R. Al-Qudimat
- Surgical Research Section, Department of Surgery, Hamad Medical Corporation, Doha, Qatar
- Department of Public Health, QU-Health, College of Health Sciences, Qatar University, Doha, Qata
| | - Mohamed B. Al Darwish
- Surgical Research Section, Department of Surgery, Hamad Medical Corporation, Doha, Qatar
| | - Saif B. Altahtamouni
- Surgical Research Section, Department of Surgery, Hamad Medical Corporation, Doha, Qatar
| | - Kalapan Singh
- Department of Nursing, Hamad Medical Corporation, Doha, Qatar
| | - Raed M. Al-Zoubi
- Surgical Research Section, Department of Surgery, Hamad Medical Corporation, Doha, Qatar
- College of Pharmacy, QU Health, Qatar University, Doha, Qata
- Department of Chemistry, Jordan University of Science and Technology, Irbid, Jordan
| | - Omar M. Aboumarzouk
- Surgical Research Section, Department of Surgery, Hamad Medical Corporation, Doha, Qatar
- College of Medicine, Qatar University, Doha, Qatar
- School of Medicine, Dentistry and Nursing, The University of Glasgow, Glasgow, UK
| | - Abdulla Al-Ansari
- Surgical Research Section, Department of Surgery, Hamad Medical Corporation, Doha, Qatar
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Pośpiech M, Kolonko A, Nieszporek T, Kozak S, Kozaczka A, Karkoszka H, Winder M, Chudek J. Transplanted kidney loss during colorectal cancer chemotherapy: A case report. World J Clin Cases 2022; 10:6647-6655. [PMID: 35979324 PMCID: PMC9294886 DOI: 10.12998/wjcc.v10.i19.6647] [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: 12/14/2021] [Revised: 03/02/2022] [Accepted: 04/22/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The overall risk of de novo malignancies in kidney transplant recipients (KTRs) is higher than that in the general population. It is associated with long-lasting exposure to immunosuppressive agents and impaired oncological vigilance due to chronic kidney disease. Colorectal cancer (CRC), frequently diagnosed in an advanced stage, is one of the most common malignancies in this cohort and is associated with poor prognosis. Still, because of the scarcity of data concerning adjuvant chemotherapy in this group, there are no clear guidelines for the specific management of the CRCs in KTRs. We present a patient who lost her transplanted kidney shortly after initiation of adjuvant chemotherapy for colon cancer. CASE SUMMARY A 36-year-old woman with a medical history of kidney transplantation (2005) because of end-stage kidney disease, secondary to chronic glomerular nephritis, and long-term immunosuppression was diagnosed with locally advanced pT4AN1BM0 (clinical stage III) colon adenocarcinoma G2. After right hemicolectomy, the patient was qualified to receive adjuvant chemotherapy that consisted of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX-4). The deterioration of kidney graft function after two cycles caused chemotherapy cessation and initiation of hemodialysis therapy after a few months. Shortly after that, the patient started palliative chemotherapy because of cancer recurrence with intraperitoneal spread. CONCLUSION Initiation of adjuvant chemotherapy for colon cancer increases the risk of rapid kidney graft loss driven also by under-immunosuppression.
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Affiliation(s)
- Marta Pośpiech
- Department of Internal Diseases and Oncological Chemotherapy, Medical University of Silesia in Katowice, Katowice 40-027, Poland
| | - Aureliusz Kolonko
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia in Katowice, Katowice 40-027, Poland
| | - Teresa Nieszporek
- Department of Nephrology, Transplantation and Internal Medicine, Mielecki Clinical Hospital of the Medical University of Silesia, Katowice 40-027, Poland
| | - Sylwia Kozak
- Department of Internal Diseases and Oncological Chemotherapy, Medical University of Silesia in Katowice, Katowice 40-027, Poland
| | - Anna Kozaczka
- Department of Internal Diseases and Oncological Chemotherapy, Mielecki Clinical Hospital, Katowice 40-027, Poland
| | - Henryk Karkoszka
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia in Katowice, Katowice 40-027, Poland
| | - Mateusz Winder
- Department of Radiology and Nuclear Medicine, Medical University of Silesia in Katowice, Katowice 40-752, Poland
| | - Jerzy Chudek
- Department of Internal Diseases and Oncological Chemotherapy, Medical University of Silesia in Katowice, Katowice 40-027, Poland
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Ashkar MH, Chen J, Shy C, Crippin JS, Chen CH, Sayuk GS, Davidson NO. Increased Risk of Advanced Colonic Adenomas and Timing of Surveillance Colonoscopy Following Solid Organ Transplantation. Dig Dis Sci 2022; 67:1858-1868. [PMID: 33973084 DOI: 10.1007/s10620-021-06987-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Accepted: 03/30/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND Detection and removal of colonic adenomatous polyps (CAP) decreases colorectal cancer (CRC) development, particularly with more or larger polyps or polyps with advanced villous/dysplastic histology. Immunosuppression following solid organ transplantation (SOT) may accelerate CAP development and progression compared to average-risk population but the benefit of earlier colonoscopic surveillance is unclear. AIMS Study the impact of maintenance immunosuppression post-SOT on developmental timing, multiplicity and pathological features of CAP, by measuring incidence of advanced CAP (villous histology, size ≥ 10 mm, ≥ 3 polyps, presence of dysplasia) post-SOT and the incidence of newly diagnosed CRC compared to average-risk age-matched population. METHODS Single-center retrospective cohort study of SOT recipients. RESULTS 295 SOT recipients were included and were compared with 291 age-matched average-risk controls. The mean interval between screening and surveillance colonoscopies between SOT and control groups was 6.3 years vs 5.9 years (p = 0.13). Post-SOT maintenance immunosuppression mean duration averaged 59.9 months at surveillance colonoscopy. On surveillance examinations, SOT recipients exhibited more advanced (≥ 10 mm) adenomas compared to matched controls (9.2% vs. 3.8%, p = 0.034; adjusted OR 2.38; 95% CI 1.07-5.30). CONCLUSION SOT recipients appear at higher risk for developing advanced CAP, suggesting that earlier surveillance should be considered.
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Affiliation(s)
- Motaz H Ashkar
- Department of Medicine, Division of Gastroenterology, School of Medicine and Barnes-Jewish Hospital, Washington University in St. Louis, 660 S Euclid Ave, St Louis, MO, 63110, USA
| | - Jacqueline Chen
- Department of Medicine, Division of Gastroenterology, School of Medicine and Barnes-Jewish Hospital, Washington University in St. Louis, 660 S Euclid Ave, St Louis, MO, 63110, USA
| | - Corey Shy
- Department of Medicine, School of Medicine and Barnes-Jewish Hospital, Washington University in St. Louis, St. Louis, MO, 63110, USA
| | - Jeffrey S Crippin
- Department of Medicine, Division of Gastroenterology, School of Medicine and Barnes-Jewish Hospital, Washington University in St. Louis, 660 S Euclid Ave, St Louis, MO, 63110, USA
| | - Chien-Huan Chen
- Department of Medicine, Division of Gastroenterology, School of Medicine and Barnes-Jewish Hospital, Washington University in St. Louis, 660 S Euclid Ave, St Louis, MO, 63110, USA
| | - Gregory S Sayuk
- Department of Medicine, Division of Gastroenterology, School of Medicine and Barnes-Jewish Hospital, Washington University in St. Louis, 660 S Euclid Ave, St Louis, MO, 63110, USA
| | - Nicholas O Davidson
- Department of Medicine, Division of Gastroenterology, School of Medicine and Barnes-Jewish Hospital, Washington University in St. Louis, 660 S Euclid Ave, St Louis, MO, 63110, USA.
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Kim M, Kim CW, Hwang S, Kim YH, Lee JL, Yoon YS, Park IJ, Lim SB, Yu CS, Kim JC, Han DJ, Lee SG. Characteristics and Prognosis of Colorectal Cancer after Liver or Kidney Transplantation. World J Surg 2021; 45:3206-3213. [PMID: 34235562 DOI: 10.1007/s00268-021-06219-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/31/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND The purpose of this study was to evaluate the characteristics and prognosis of de novo CRC patients who underwent liver or kidney transplantation. METHODS We retrospectively reviewed the medical records of 66 de novo CRC patients selected from 8,734 liver transplant (LT) or kidney transplant (KT) recipients. We analyzed characteristics and survival outcomes of de novo CRC patients and sporadic CRC patients who underwent radical surgery with stage I-III in Asan Medical Center between 2005 and 2016. Survival outcomes were analyzed via the 1:4 matching method. RESULTS The standard incidence ratio (SIR) of de novo CRC in KT recipients is 1.67 in men and 2.54 in women. That in LT recipients is 3.10 in men and 2.25 in women. Compared with sporadic CRC patients, de novo CRC patients had more colon cancer than rectal cancer (p=0.041). In 9 patients (13.6%), CRC was diagnosed within one year after transplantation, 21 patients (31.8%) were diagnosed between 1-5 years, and the remaining 36 patients (54.6%) were diagnosed thereafter. There were no significant differences in recurrence-free survival and overall survival between the two groups (p=0.211 and p=0.324, respectively). CONCLUSIONS The risk of developing de novo CRC in transplant recipients was higher than in the general population. The survival outcome of de novo CRC was no different compared with the sporadic CRC. Therefore, regular surveillance is essential for timely diagnosis and treatment for transplantation patients. A large prospective study for an intense CRC surveillance program in transplantation patients is needed.
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Affiliation(s)
- Minsung Kim
- Department of Colon & Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Chan Wook Kim
- Department of Colon & Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.
| | - Shin Hwang
- Department of Hepatobiliary & Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Young Hoon Kim
- Department of Kidney and Pancreas Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Jong Lyul Lee
- Department of Colon & Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Yong Sik Yoon
- Department of Colon & Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - In Ja Park
- Department of Colon & Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Seok-Byung Lim
- Department of Colon & Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Chang Sik Yu
- Department of Colon & Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Jin Cheon Kim
- Department of Colon & Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Duck Jong Han
- Department of Kidney and Pancreas Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Sung-Gyu Lee
- Department of Hepatobiliary & Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
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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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Weaver L, Parsikia A, Ortiz J. Colorectal Resection in Transplant Centers Benefits Kidney But Not Pancreas Transplant Recipients. Int J Angiol 2021; 30:139-147. [PMID: 34054272 DOI: 10.1055/s-0041-1727137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
As graft and patient survival rates improve, transplant recipients are likely to undergo colorectal surgery in their lifetime. Current literature on the surgical outcomes of colorectal resection in kidney and pancreas transplant recipients is sparse. This investigation identifies areas of surgical risk for kidney, pancreas, and pancreas-kidney transplant recipients undergoing colorectal resection at transplant and teaching centers. Multivariate logistic regression and linear regression tests computed odds ratios (OR) and coefficients of the linear regression using National Inpatient Sample data from 2005 to 2014 to identify differences in mortality, morbidity, length of stay (LOS), and total hospital charges among people with pancreas transplant alone (PTx), kidney transplant alone (KTx), pancreas and kidney transplant (PKTx), and nontransplant (non-Tx) undergoing colorectal resection in transplant and teaching centers. Of the 2,737,454 individuals who underwent colorectal resection, 138 PTx, 3,874 KTx, 130 PKTx, and 2,733,312 non-Tx met the inclusion criteria. Overall KTx, PTx, and PKTx were not more likely to suffer a mortality. However, PTx were more likely to suffer a mortality in transplant and teaching centers. Overall, PTx and PKTx had significantly higher morbidity odds ratios (PTx OR: 2.268, p = 0.002; PKTx OR: 2.578, p < 0.001) along with longer LOS and higher total hospital charges. KTx incurred no increased morbidity risk in transplant centers. Surgeons and transplant recipients should be aware of the increased morbidity and mortality risks when considering colorectal resection at different center types.
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Affiliation(s)
- Lauren Weaver
- Department of Surgery, University of Minnesota, Minneapolis, Minnesota
| | - Afshin Parsikia
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Jorge Ortiz
- Department of Surgery, Albany Medical Center, Albany, New York
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Dameworth JL, Colburn L, Corrigan D, Driessen R, Chapple K, Gagliano RA, Walia R, Row D. Colorectal Cancer Prevention in Lung Transplant Recipients: The Need for an Enhanced Surveillance Protocol. J Am Coll Surg 2021; 232:717-725. [PMID: 33486129 DOI: 10.1016/j.jamcollsurg.2020.12.053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 12/18/2020] [Accepted: 12/21/2020] [Indexed: 11/28/2022]
Abstract
BACKGROUND Solid organ transplant recipients are at increased risk for noncutaneous neoplasms, including colorectal cancer (CRC). We evaluated precancerous lesions detected by post-transplant surveillance colonoscopy to infer the rate at which new adenomas develop in this population. STUDY DESIGN We reviewed all patients who underwent lung transplant between January 2013 and August 2017 at our institution. Those with post-transplant survival <1 year, personal history of CRC, previous lung transplant, and lack of pretransplant colonoscopy were excluded. RESULTS During the study period, 411 patients underwent lung transplant; 237 met inclusion criteria. Median age at transplant was 63.6 (interquartile range [IQR] 59.2-68.3) years. Most recipients were immunosuppressed with a combination of prednisone, tacrolimus, and mycophenolate mofetil. At least 1 adenoma was found in 92 patients (38.8%) pretransplant and in 118 patients (49.8%) from 1 to 5 years post-transplant, with 68.6% identified at 1 year. Most adenomas were identified proximal to the splenic flexure. Multiple (≥3) adenomas were found in 31.4% of positive colonoscopies. Within 5 years after transplant, patients with a positive pretransplant colonoscopy had significantly more positive post-transplant colonoscopies than patients with a negative pretransplant colonoscopy (63.0% vs 41.4%, p < 0.001). No de novo CRC was identified. CONCLUSIONS Lung transplant recipients have a significantly higher risk of adenoma formation than average-risk adults (25%-30% national detection rate). This increase occurs in the early post-transplant period (within 3 years). An enhanced CRC surveillance protocol for lung transplant recipients is needed.
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Affiliation(s)
| | - Luc Colburn
- Creighton University School of Medicine, Phoenix, AZ
| | | | | | - Kristina Chapple
- Department of Surgery, St Joseph's Hospital and Medical Center, Phoenix, AZ
| | - Ronald A Gagliano
- Department of Surgery, St Joseph's Hospital and Medical Center, Phoenix, AZ
| | - Rajat Walia
- Norton Thoracic Institute, St Joseph's Hospital and Medical Center, Phoenix, AZ
| | - David Row
- Department of Surgery, St Joseph's Hospital and Medical Center, Phoenix, AZ.
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9
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Abstract
Cancer is an important cause of morbidity and mortality after liver transplantation and can occur through three mechanisms: recurrence of a recipient's pre-transplant malignancy, donor-related transmission and de novo development. Currently, the decision to list a patient with a history of malignancy is an individual one. Screening guidelines for potential donors and for recipients after transplant are still widely based on general population guidelines, while the role of chronic immunosuppression remains controversial. These shortcomings mean that patients present at diagnosis with advanced stages of the disease, often precluding curative treatments. The present review summarizes current recommendations for the screening of recipients and donors for pre- and post-transplant malignancies, and current management of recipients who develop cancer after a liver transplant.
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10
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Gastrointestinal Pathologies in Patients After Successful Renal Transplantation. Transplant Proc 2020; 52:2412-2416. [PMID: 32713818 DOI: 10.1016/j.transproceed.2020.02.121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 02/13/2020] [Indexed: 11/23/2022]
Abstract
BACKGROUND Kidney transplantation (KT) is the most desired and cost-effective modality of renal replacement therapy for patients with chronic kidney failure. KT protects the patient from complications that may develop during chronic dialysis. Unfortunately, evidence also suggests that KT patients are more prone to developing cancer than healthy persons. Many complications after renal transplantation can be prevented if they are detected early. The aim of this study was to evaluate the prevalence of gastrointestinal pathologies in patients after KT. METHODS Adult patients after KT who are under the care of the Outpatient Department of Nephrology at the Medical University of Gdańsk, Poland, received alarm symptom questionnaires and referral for testing for the presence of fecal occult blood. Then, in 58 selected patients (36 men and 22 women), endoscopic examination was performed. Mean age was 57.34 ± 10.1 (range, 35-83) years. RESULTS Out of 940 patients after KT, resting under supervision of the Outpatient Department, 208 patients completed the questionnaire and 118 gave a stool sample for testing: 40 results were positive. After analyzing the questionnaires and stool results, 100 patients qualified for further investigation. The endoscopic examination had been performed so far in 58 patients and revealed gastritis and/or duodenitis in 49 patients, diverticular colon disease in 26, esophagitis in 8, colon polyps in 16, stomach polyps in 4, inflammatory bowel disease in 12, and cancers in 3. CONCLUSIONS The preliminary results indicate that patients after KT have significant risk of gastrointestinal pathologies and require detailed diagnostic endoscopy.
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11
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Halabi WJ, Jafari MD, Nguyen VQ, Carmichael JC, Mills S, Pigazzi A, Stamos MJ, Foster CE. Colorectal Surgery in Kidney Transplant Recipients: A Decade of Trends and Outcomes in the United States. Am Surg 2020. [DOI: 10.1177/000313481307901015] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
There is paucity of data evaluating the trends and outcomes of colorectal surgery (CRS) in kidney transplant recipients (KTRs). Using the Nationwide Inpatient Sample 2001 to 2010, a retrospective review of CRS performed in KTRs was performed. Trends, demographics, indications, and outcomes were examined for elective and emergent cases and compared with the general population (GP) on multivariate logistic regression. A total of 2616 KTRs underwent CRS, 50 per cent of which were done emergently. KTRs developed colon and rectal cancer at a younger age and had significantly higher incidence of comorbidities compared with the GP. Diverticular disease was the most common indication for surgery (48%) followed by cancer (30.6%). Compared with the GP, KTRs had higher rates of mortality (6.29 vs 3.64%), wound complications (8.02 vs 5.37%), and acute renal failure (ARF) (17.14 vs 7.10%) (all P < 0.05). No difference was seen in the incidence of anastomotic leak. On multivariate analysis, KTRs had higher associated odds of ARF (odds ratio, 2.02; P < 0.001), whereas the odds of mortality, wound, and anastomotic complications were similar to the GP. Emergency surgery in KTRs was associated with worse outcomes compared with the elective setting. KTRs undergoing CRS have unique characteristics that are different than the GP. They are at an increased risk of complications, especially acute renal failure.
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Affiliation(s)
- Wissam J. Halabi
- Department of Surgery, University of California, Irvine School of Medicine, Irvine, California
| | - Mehraneh D. Jafari
- Department of Surgery, University of California, Irvine School of Medicine, Irvine, California
| | - Vinh Q. Nguyen
- Department of Statistics, University of California Irvine, Irvine, California
| | - Joseph C. Carmichael
- Department of Surgery, University of California, Irvine School of Medicine, Irvine, California
| | - Steven Mills
- Department of Surgery, University of California, Irvine School of Medicine, Irvine, California
| | - Alessio Pigazzi
- Department of Surgery, University of California, Irvine School of Medicine, Irvine, California
| | - Michael J. Stamos
- Department of Surgery, University of California, Irvine School of Medicine, Irvine, California
| | - Clarence E. Foster
- Department of Surgery, University of California, Irvine School of Medicine, Irvine, California
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12
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Smedman TM, Guren TK, Line PD, Dueland S. Transplant oncology: assessment of response and tolerance to systemic chemotherapy for metastatic colorectal cancer after liver transplantation - a retrospective study. Transpl Int 2019; 32:1144-1150. [PMID: 31209941 DOI: 10.1111/tri.13471] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 05/09/2019] [Accepted: 06/11/2019] [Indexed: 01/03/2023]
Abstract
Solid organ recipients have a 2-5 fold increased risk of malignancy compared to the general population. Because of the broader indications for transplantation, it is anticipated that an increasing number of organ graft recipients will present with malignancy. There are limited data about responses and tolerance to chemotherapy in solid organ transplanted patients. Twenty-three of 46 colorectal cancer (CRC) patients with nonresectable liver metastases who had undergone liver transplantation (LT) in three different studies were included. All patients had received chemotherapy both prior to LT and after LT, at recurrence of metastatic CRC (mCRC). Adverse reactions (grades 3-4) and clinical and radiological outcome were retrospectively registered. Overall survival was determined from start of palliative chemotherapy after LT. No graft rejection was observed. Chemotherapy for mCRC was overall well-tolerated and there was no increased bone marrow toxicity registered after LT; however, mucositis and diarrhea were more frequent in post-LT chemotherapy. Median overall survival from start of palliative chemotherapy after LT was 13 months. No graft loss was observed when chemotherapy for mCRC was given to LT recipients who had developed nonresectable metastases. Overall, the chemotherapy for mCRC was well-tolerated, induced responses, and long-term survival was obtained in some patients.
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Affiliation(s)
- Tor Magnus Smedman
- Department of Oncology, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | | | - Pål-Dag Line
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Svein Dueland
- Department of Oncology, Oslo University Hospital, Oslo, Norway
- Experimental Transplantation and Malignancy Research Group, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
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13
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Vazquez Guillamet R. Chronic Obstructive Pulmonary Disease and the Optimal Timing of Lung Transplantation. MEDICINA (KAUNAS, LITHUANIA) 2019; 55:E646. [PMID: 31561607 PMCID: PMC6843760 DOI: 10.3390/medicina55100646] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Revised: 09/17/2019] [Accepted: 09/23/2019] [Indexed: 11/29/2022]
Abstract
Chronic obstructive pulmonary disease (COPD) accounts for the largest proportion of respiratory deaths worldwide and was historically the leading indication for lung transplantation. The success of lung transplantation procedures is measured as survival benefit, calculated as survival with transplantation minus predicted survival without transplantation. In chronic obstructive pulmonary disease, it is difficult to show a clear and consistent survival benefit. Increasing knowledge of the risk factors, phenotypical heterogeneity, systemic manifestations, and their management helps improve our ability to select candidates and list those that will benefit the most from the procedure.
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14
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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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15
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George AT, Leong M, Shokouh-Amiri M, Benedetti E, Carroll RE. Accelerated Colorectal Polyposis in an Immunosuppressed Patient With a Small Bowel Transplant Treated With Teduglutide: Case Report and Review of Literature. Clin Colorectal Cancer 2019; 18:e275-e279. [PMID: 31176580 DOI: 10.1016/j.clcc.2019.02.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Revised: 02/18/2019] [Accepted: 02/20/2019] [Indexed: 12/15/2022]
Affiliation(s)
- Alvin T George
- Intestinal Rehabilitation and Transplant Center, Departments of Medicine and Surgery, University of Illinois at Chicago, Chicago, IL
| | - Michelle Leong
- Intestinal Rehabilitation and Transplant Center, Departments of Medicine and Surgery, University of Illinois at Chicago, Chicago, IL
| | | | - Enrico Benedetti
- Intestinal Rehabilitation and Transplant Center, Departments of Medicine and Surgery, University of Illinois at Chicago, Chicago, IL
| | - Robert E Carroll
- Intestinal Rehabilitation and Transplant Center, Departments of Medicine and Surgery, University of Illinois at Chicago, Chicago, IL.
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16
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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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17
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Triplette M, Crothers K, Mahale P, Yanik EL, Valapour M, Lynch CF, Schabath MB, Castenson D, Engels EA. Risk of lung cancer in lung transplant recipients in the United States. Am J Transplant 2019; 19:1478-1490. [PMID: 30565414 PMCID: PMC6872188 DOI: 10.1111/ajt.15181] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Revised: 10/23/2018] [Accepted: 11/06/2018] [Indexed: 01/25/2023]
Abstract
Lung transplant recipients have an increased risk of lung cancer that is poorly understood. Prior studies are largely descriptive and single-center, and have not examined risk factors or outcomes in this population. This registry-linkage study utilized matched transplant and cancer registry data from 17 US states/regions during 1987-2012. We used standardized incidence ratios (SIRs) to compare incidence with the general population, Poisson models to identify lung cancer risk factors, and Cox models to compare survival after diagnosis. Lung cancer risk was increased among lung recipients (SIR 4.8, 95% confidence interval [CI] 4.1-5.5). Those with single lung transplant had 13-fold (95% CI 11-15) increased risk in the native lung. Native lung cancer risk factors included age, prior smoking, time since transplant, and idiopathic pulmonary fibrosis. Compared with cases in the general population, lung cancers in recipients were more frequently localized stage (P = .02) and treated surgically (P = .05). However, recipients had higher all-cause (adjusted hazard ratio 1.90, 95% CI 1.52-2.37) and cancer-specific mortality (adjusted hazard ratio 1.67, 95% CI 1.28-2.18). In conclusion, lung cancer risk is increased after lung transplant, especially in the native lung of single lung recipients. Traditional risk factors are associated with lung cancer in these patients. Lung cancer survival is worse among lung recipients despite earlier diagnosis.
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Affiliation(s)
- Matthew Triplette
- Department of Medicine, University of Washington, Seattle, WA, USA
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | | | - Parag Mahale
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Elizabeth L. Yanik
- Department of Orthopaedic Surgery, Washington University in St. Louis, St. Louis, MO, USA
| | - Maryam Valapour
- Respiratory Institute, Cleveland Clinic, Cleveland, OH, USA
- Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, Minneapolis, MN, USA
| | - Charles F. Lynch
- Department of Epidemiology, University of Iowa, Iowa City, IA, USA
| | - Matthew B. Schabath
- Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
| | | | - Eric A. Engels
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
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18
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Outcomes of patients who developed subsequent solid cancer after hematopoietic cell transplantation. Blood Adv 2019; 2:1901-1913. [PMID: 30087108 DOI: 10.1182/bloodadvances.2018020966] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2018] [Accepted: 07/05/2018] [Indexed: 02/07/2023] Open
Abstract
To characterize the outcomes of patients who developed a particular subsequent solid cancer after hematopoietic cell transplantation (HCT), age at cancer diagnosis, survival, and causes of death were compared with the respective primary cancer in the general population, using data from the national HCT registry and population-based cancer registries in Japan. Among 31 867 patients who underwent a first HCT between 1990 and 2013 and had progression-free survival at 1 year, 713 patients developed subsequent solid cancer. The median age at subsequent solid cancer diagnosis was 55 years, which was significantly younger than the 67 years for primary cancer patients in the general population (P < .001). The overall survival probability was 60% at 3 years after diagnosis of subsequent solid cancer and differed according to cancer type. Development of most solid cancers was associated with an increased risk of subsequent mortality after HCT. Subsequent solid cancers accounted for 76% of causes of death. Overall survival probabilities adjusted for age, sex, and year of diagnosis were lower in the HCT population than in the general population for colon, bone/soft tissue, and central nervous system cancers and did not differ statistically for other cancers. In conclusion, most subsequent solid cancers occurred at younger ages than primary cancers, emphasizing the need for cancer screening at younger ages. Subsequent solid cancers showed similar or worse survival compared with primary cancers. Biological and genetic differences between primary and subsequent solid cancers remain to be determined.
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19
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Rompianesi G, Ravikumar R, Jose S, Allison M, Athale A, Creamer F, Gunson B, Manas D, Monaco A, Mirza D, Owen N, Roberts K, Sen G, Srinivasan P, Wigmore S, Fusai G, Fernando B, Burroughs A, Tsochatzis E. Incidence and outcome of colorectal cancer in liver transplant recipients: A national, multicentre analysis on 8115 patients. Liver Int 2019; 39:353-360. [PMID: 30129181 DOI: 10.1111/liv.13947] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Revised: 08/02/2018] [Accepted: 08/16/2018] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS De novo malignancies after liver transplantation represent one of the leading causes of death in the long-term. It remains unclear whether liver transplant recipients have an increased risk of colorectal cancer and whether this negatively impacts on survival, particularly in those patients affected by primary sclerosing cholangitis and ulcerative colitis. METHODS In this national multicentre cohort retrospective study, the incidence of colorectal cancer in 8115 evaluable adult patients undergoing a liver transplantation between 1 January 1990 and 31 December 2010 was compared to the incidence in the general population through standardised incidence ratios. RESULTS Fifty-two (0.6%) cases of colorectal cancer were identified at a median of 5.6 years postliver transplantation, predominantly grade 2 (76.9%) and stage T3 (50%) at diagnosis. The incidence rate of colorectal cancer in the whole liver transplant population was similar to the general UK population (SIR: 0.92), but significantly higher (SIR: 7.0) in the group of patients affected by primary sclerosing cholangitis/ulcerative colitis. One-, five- and ten-year survival rates from colorectal cancer diagnosis were 71%, 48% and 31%, respectively, and the majority of colorectal cancer patients died of cancer-specific causes. CONCLUSIONS Liver transplantation alone is not associated with an increased risk of colorectal cancer development. The primary sclerosing cholangitis/ulcerative colitis liver transplant population showed a significantly higher risk of colorectal cancer development than the general population, with a high proportion of advanced stage at diagnosis and a reduced patient survival.
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Affiliation(s)
- Gianluca Rompianesi
- Sheila Sherlock Liver Unit, UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Reena Ravikumar
- Sheila Sherlock Liver Unit, UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Sophie Jose
- Research Department of Infection and Population Health, University College London, London, UK
| | - Michael Allison
- Cambridge Transplant Unit, Cambridge Biomedical Research Centre, Cambridge University Hospitals, Cambridge, UK
| | - Anuja Athale
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Felicity Creamer
- Department of HPB and Transplant Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Bridget Gunson
- The Liver Unit, University Hospitals Birmingham and NIHR Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, UK
| | - Derek Manas
- Institute of Transplantation, Freeman Hospital, Newcastle, UK
| | - Andrea Monaco
- Sheila Sherlock Liver Unit, UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Darius Mirza
- The Liver Unit, University Hospitals Birmingham and NIHR Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, UK
| | - Nicola Owen
- Cambridge Transplant Unit, Cambridge Biomedical Research Centre, Cambridge University Hospitals, Cambridge, UK
| | - Keith Roberts
- The Liver Unit, University Hospitals Birmingham and NIHR Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, UK
| | - Gourab Sen
- Institute of Transplantation, Freeman Hospital, Newcastle, UK
| | | | - Stephen Wigmore
- Department of HPB and Transplant Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Giuseppe Fusai
- Sheila Sherlock Liver Unit, UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Bimbi Fernando
- Sheila Sherlock Liver Unit, UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Andrew Burroughs
- Sheila Sherlock Liver Unit, UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Emmanuel Tsochatzis
- Sheila Sherlock Liver Unit, UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
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20
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Kobiela J, Dobrzycka M, Danielewicz R, Jończyk J, Łachiński AJ, Śledziński Z, Dębska-Ślizień A. Colonoscopy as Part of Pre-Transplant Work-Up in Successful Kidney Transplant Candidates: Single-Center Experience and Review of Literature. Ann Transplant 2018; 23:782-788. [PMID: 30409961 PMCID: PMC6247820 DOI: 10.12659/aot.910658] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background Screening colonoscopy is not obligatory in kidney pre-transplant work-up guidelines. According to recommendations, only transplant recipients over age 50 years should be screened. The aim of this study was to characterize endoscopic findings revealed as part of pre-transplant work-up. Material/Methods We retrospectively reviewed pre-transplant work-up charts of 434 adult patients who received a cadaveric donor kidney transplantation (KT) from 2012 to 2015. Endoscopic findings analysis with age subgroup (<50 and ≥50) analysis were performed. Results Out of 434 of patients that underwent KT, 29% have had a colonoscopy. In 75.6% of those, pathologies were found. Hemorrhoids were found in 33% and polyps in 30.7% of patients. Adenoma detection rate (ADR) was 18.1% (67.5% distal predominance). Advanced ADR was 10.2% (distal predominance). Diverticulosis was found in 28.3% of patients and ulcerative colitis was found in 2.4%. In age subgroup analysis, ADR was higher in patients ≥50 years compared to those <50 years (21.6% vs. 4%; p=0.041). Conclusions Colonoscopy as part of pre-transplant work-up enables removal of precancerous lesions and management of benign findings. All candidates meeting criteria for the general population should be screened. Patients under age 50 years could also benefit from colonoscopy as part of the pre-transplant work-up. Therefore, we suggest that baseline colonoscopy should be included in pre-transplant work-up guidelines for all patients, regardless of age. However, further studies are needed to confirm this recommendation.
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Affiliation(s)
- Jarek Kobiela
- Department of General, Endocrine, and Transplant Surgery, Medical University of Gdańsk, Gdańsk, Poland
| | - Małgorzata Dobrzycka
- Department of General, Endocrine, and Transplant Surgery, Medical University of Gdańsk, Gdańsk, Poland
| | - Roman Danielewicz
- Department of Surgical and Transplant Nursing, Medical University of Warsaw, Warsaw, Poland
| | - Justyna Jończyk
- Department of General, Endocrine, and Transplant Surgery, Medical University of Gdańsk, Gdańsk, Poland
| | - Andrzej J Łachiński
- Department of General, Endocrine, and Transplant Surgery, Medical University of Gdańsk, Gdańsk, Poland
| | - Zbigniew Śledziński
- Department of General, Endocrine, and Transplant Surgery, Medical University of Gdańsk, Gdańsk, Poland
| | - Alicja Dębska-Ślizień
- Department of Nephrology, Transplantology, and Internal Medicine, Medical University of Gdańsk, Gdańsk, Poland
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21
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Outcomes Following Colorectal Resection in Kidney Transplant Recipients. J Gastrointest Surg 2018; 22:1603-1610. [PMID: 29736667 PMCID: PMC6222018 DOI: 10.1007/s11605-018-3801-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Accepted: 04/25/2018] [Indexed: 01/31/2023]
Abstract
BACKGROUND Kidney transplant recipients (KTR) are at increased risk of requiring colorectal resection compared to the general population. Given the need for lifelong immunosuppression and the physiologic impact of years of renal replacement, we hypothesized that colorectal resection may be riskier for this unique population. METHODS We investigated the differences in mortality, morbidity, length of stay (LOS), and cost between 2410 KTR and 1,433,437 non-KTR undergoing colorectal resection at both transplant and non-transplant centers using the National Inpatient Sample between 2000 and 2013, adjusting for patient and hospital level factors. RESULTS In hospital, mortality was higher for KTR in comparison to non-KTR (11.1 vs 4.3%, p < 0.001; adjusted odds ratio [aOR] 2.683.594.81) as were overall complications (38.5 vs 31.5%, p = 0.001; aOR 1.081.301.56). LOS was significantly longer (10 vs 7 days, p < 0.001; ratio 1.421.531.65) and cost was significantly greater ($23,056 vs $14,139, p < 0.001; ratio 1.421.541.63) for KTR compared to non-KTR. While LOS was longer for KTR undergoing resection at transplant centers compared to non-transplant centers (aOR 1.68 vs 1.53, p = 0.03), there were no statistically significant differences in mortality, overall morbidity, or cost by center type. CONCLUSIONS KTR have higher mortality, higher incidence of overall complications, longer LOS, and higher cost than non-KTR following colorectal resection, regardless of center type. Physicians should consider these elevated risks when planning for surgery in the KTR population and counsel patients accordingly.
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Balhareth A, Reynolds IS, Solon JG, Harte EG, Boland F, O'Sullivan JM, Burke JP, Little D, McNamara DA. Thirty-seven-year Population-based Study of Colorectal Cancer Rates in Renal Transplant Recipients in Ireland. Transplant Proc 2018; 50:3434-3439. [PMID: 30577217 DOI: 10.1016/j.transproceed.2018.07.031] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 07/08/2018] [Accepted: 07/18/2018] [Indexed: 01/15/2023]
Abstract
BACKGROUND Renal transplantation is associated with an increased risk of neoplasia, including colorectal cancer (CRC). Advances in surgical techniques and immunosuppressive medications have resulted in increased survival rates of both patients and grafts, but the incidence of CRC in the Irish renal transplant population is currently unknown. The aim of this study is to review the incidence of CRC in the Irish renal transplant population and compare it to the general population. METHODS A retrospective review of a prospectively maintained database of all renal transplant recipients in Ireland between January 1980 and July 2017 was performed. RESULTS Thirty-three out of 4230 transplant recipients (men = 20, women = 13) developed CRC subsequent to transplantation and were eligible for inclusion in the series. The mean age at transplantation was 51.5 years, with patients developing CRC on average 10.9 years post-transplantation; 6.1% (n = 2/33) had stage IV disease at diagnosis. The majority of patients (87.8%) had a pathologic T stage of T3/T4 and 45.5% had involvement of locoregional lymph nodes (N1/N2); 42.4% also had a mucinous component at histopathologic assessment. The incidence of CRC was higher in the transplant population compared to the general population. CONCLUSION This is the first population-based assessment of CRC development in the Irish renal transplant population. Our data suggest that Irish transplant recipients have an increased risk of being diagnosed with a more advanced tumor than the general population, with most being diagnosed almost a decade after transplantation. This highlights the need for increased awareness among patients and clinicians and the potential need for coordinated lifelong surveillance of this patient population to ensure early detection and treatment.
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Affiliation(s)
- A Balhareth
- Department of Colorectal Surgery, Beaumont Hospital, Dublin, Ireland
| | - I S Reynolds
- Department of Colorectal Surgery, Beaumont Hospital, Dublin, Ireland
| | - J G Solon
- Department of Colorectal Surgery, Beaumont Hospital, Dublin, Ireland
| | - E Gibbons Harte
- Department of Colorectal Surgery, Beaumont Hospital, Dublin, Ireland
| | - F Boland
- Data Science Centre and HRB Centre for Primary Care Research, Royal College of Surgeons, Dublin, Ireland
| | - J M O'Sullivan
- Department of Urology and Transplant Surgery, Beaumont Hospital, Dublin, Ireland
| | - J P Burke
- Department of Colorectal Surgery, Beaumont Hospital, Dublin, Ireland; Royal College of Surgeons in Ireland, Dublin, Ireland
| | - D Little
- Department of Urology and Transplant Surgery, Beaumont Hospital, Dublin, Ireland
| | - D A McNamara
- Department of Colorectal Surgery, Beaumont Hospital, Dublin, Ireland; Royal College of Surgeons in Ireland, Dublin, Ireland.
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Dueland S, Foss A, Solheim JM, Hagness M, Line PD. Survival following liver transplantation for liver-only colorectal metastases compared with hepatocellular carcinoma. Br J Surg 2018; 105:736-742. [PMID: 29532908 DOI: 10.1002/bjs.10769] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Revised: 10/24/2017] [Accepted: 10/26/2017] [Indexed: 02/11/2025]
Abstract
BACKGROUND Liver transplantation is considered the standard of care for patients with hepatocellular carcinoma (HCC) within the Milan criteria. Liver transplantation in patients with unresectable colorectal cancer with liver-only disease has been shown to be associated with a 5-year overall survival rate of 56 per cent, compared with 9 per cent in patients receiving standard palliative chemotherapy. The aim of the present study was to compare disease-free (DFS) and overall (OS) survival after liver transplantation in patients with HCC and those with colorectal metastases. METHODS Data were collected from the SEcondary CAncer (SECA) study database and an institutional (national) database of patients undergoing liver transplantation for HCC; all liver-transplanted patients were included. Patients with colorectal metastases treated by liver transplantation were divided into high- and low-risk groups for mortality based on carcinoembryonic antigen levels, response to chemotherapy, largest lesion at time of transplantation and time from primary surgery to transplantation. RESULTS Patients with colorectal metastases had a median of 8 lesions, compared with 1 in patients with HCC within the Milan criteria. DFS was shorter in both the high-risk and the low-risk colorectal cancer groups compared with that in patients with HCC. The 5-year OS rate in the low-risk colorectal cancer group was 75 per cent, compared with 76 per cent in patients with HCC within the Milan criteria. The 5-year OS rate in patients with HCC beyond the Milan criteria was 56 per cent. CONCLUSION The low-risk group of patients with colorectal cancer and unresectable liver-only disease had a 5-year OS rate following liver transplantation similar to that of patients with HCC with lesions within the Milan criteria.
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Affiliation(s)
- S Dueland
- Department of Oncology, Oslo University Hospital, Oslo, Norway
- Department of Mathematics and Natural Science, University of Stavanger, Stavanger, Norway
| | - A Foss
- Section for Transplantation Surgery, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - J M Solheim
- Section for Transplantation Surgery, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - M Hagness
- Section for Transplantation Surgery, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - P-D Line
- Section for Transplantation Surgery, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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Grut H, Solberg S, Seierstad T, Revheim ME, Egge TS, Larsen SG, Line PD, Dueland S. Growth rates of pulmonary metastases after liver transplantation for unresectable colorectal liver metastases. Br J Surg 2018; 105:295-301. [PMID: 29168565 DOI: 10.1002/bjs.10651] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Revised: 06/21/2017] [Accepted: 06/23/2017] [Indexed: 02/11/2025]
Abstract
BACKGROUND The previously reported SECA study demonstrated a dramatic 5-year survival improvement in patients with unresectable colorectal liver metastases (CLM) treated with liver transplantation (LT) compared with chemotherapy. The objective of this study was to assess whether immunosuppressive therapy accelerates the growth of pulmonary metastases in patients transplanted for unresectable CLM. METHODS Chest CT scans from 11 patients in the SECA study resected for 18 pulmonary metastases were reviewed retrospectively. Tumour diameter, volume and CT characteristics were registered and tumour volume doubling time was calculated. Findings in the SECA group were compared with those of a control group consisting of 12 patients with non-transplanted rectal cancer resected for 26 pulmonary metastases. Disease-free survival (DFS) and overall survival (OS) after first pulmonary resection were determined. RESULTS Median doubling time based on tumour diameter and volume in the SECA and control groups were 125 and 130 days (P = 0·658) and 110 and 129 days (P = 0·632) respectively. The metastases in both groups were distributed to all lung lobes and were mostly peripheral. Median DFS after LT in the SECA group and after primary pelvic surgery in the control group was 17 (range 6-42) and 18 (2-57) months respectively (P = 0·532). In the SECA group, estimated 5-year DFS and OS rates after first pulmonary resection were 39 and 51 per cent respectively. CONCLUSION Patients treated by LT for unresectable CLM have a good prognosis following resection of pulmonary metastases. Doubling time did not appear to be worse with the immunosuppression used after LT.
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Affiliation(s)
- H Grut
- Division of Radiology and Nuclear Medicine, University of Oslo, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - S Solberg
- Department of Thoracic Surgery, University of Oslo, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - T Seierstad
- Division of Radiology and Nuclear Medicine, University of Oslo, Oslo, Norway
| | - M E Revheim
- Division of Radiology and Nuclear Medicine, University of Oslo, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - T S Egge
- Division of Radiology and Nuclear Medicine, University of Oslo, Oslo, Norway
| | - S G Larsen
- Department of Gastroenterological Surgery, University of Oslo, Oslo, Norway
| | - P D Line
- Department of Transplantation Medicine, University of Oslo, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - S Dueland
- Department of Oncology, Oslo University Hospital, Oslo, Norway
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25
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Prenner S, Levitsky J. Comprehensive Review on Colorectal Cancer and Transplant. Am J Transplant 2017; 17:2761-2774. [PMID: 28471512 DOI: 10.1111/ajt.14340] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2017] [Revised: 04/19/2017] [Accepted: 04/23/2017] [Indexed: 01/25/2023]
Abstract
Colorectal cancer (CRC) is a common malignancy worldwide. Some studies suggest that organ recipients are at a higher risk for CRC than the general population. The underlying transplant indications and their inherent risk factors for CRC may drive the variation in incidence rates that are seen in patients receiving different allografts. Recipients with cystic fibrosis are now recognized as a population at high risk for CRC at a young age. Transplant recipients have high mortality following a CRC diagnosis, even if it is detected at an early stage. Certain types of immunosuppression have been shown to accelerate cancer transformation and may contribute to the more aggressive phenotype seen in organ recipients. Given the high incidence and progressive nature of posttransplant CRC, shorter screening intervals with a modality that can detect early-stage polyps may be essential to prevent mortality. Future research is needed to better elucidate the role of immunosuppression in carcinogenesis. This comprehensive review examines CRC risk, screening, and management specific to organ transplant candidates and recipients.
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Affiliation(s)
- S Prenner
- Division of Gastroenterology & Hepatology, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - J Levitsky
- Division of Gastroenterology & Hepatology, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL
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Mussin N, Oh SC, Lee KW, Park MY, Seo S, Yi NJ, Kim H, Yoon KC, Ahn SW, Kim HS, Hong SK, Oh DK, Suh KS. Sirolimus and Metformin Synergistically Inhibits Colon Cancer In Vitro and In Vivo. J Korean Med Sci 2017; 32:1385-1395. [PMID: 28776332 PMCID: PMC5546956 DOI: 10.3346/jkms.2017.32.9.1385] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Accepted: 06/10/2017] [Indexed: 01/26/2023] Open
Abstract
We estimated the effect of various immunosuppressants (ISs) and metformin (M) to provide theoretical background of optimal therapeutic strategy for de novo colon cancer after liver transplantation (LT). Three colon cancer cell lines (HT29, SW620, and HCT116) were used in in vitro studies. HT29 was also used in BALB/c-nude mice animal models. Following groups were used in both in vitro and in vivo studies: sirolimus (S), tacrolimus (T), cyclosporin A (CsA), M, metformin/sirolimus (Met/S), metformin/tacrolimus (Met/T), and metformin/cyclosporin A (Met/CsA). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed and western blot analyses were performed for mTOR pathway proteins, apoptosis proteins, and epithelial-mesenchymal-transition (EMT) proteins. Tumor volume was measured for 4 weeks after inoculation. MTT-assay revealed significant cell viability inhibition in all 3 colon cancer cell lines in groups of S, M, and Met/S. Of note, group Met/S showed synergistic effect compare to M or S group. Western blot analysis showed significant low levels of all investigated proteins in groups of S and Met/S in both in vitro and in vivo experiment. Tumor growth was significantly inhibited only in the Met/S group. Combination of Met and S showed the most potent inhibition in all colon cancer cell lines. This finding might have application for de novo colon cancer.
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Affiliation(s)
- Nadiar Mussin
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
- Department of General Surgery, Astana City Hospital #1, Astana, Kazakhstan
| | - Seung Cheol Oh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kwang Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
| | - Min Young Park
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Sooin Seo
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Nam Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hyeyoung Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung Chul Yoon
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Sung Woo Ahn
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hyo Sin Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Suk Kyun Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Kyu Oh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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Ma AT, Therrien A, Giard JM, von Renteln D, Bouin M. Alcoholic liver disease is a strong predictor of colorectal polyps in liver transplant recipients. Endosc Int Open 2017; 5:E918-E923. [PMID: 28924600 PMCID: PMC5597935 DOI: 10.1055/s-0043-114660] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2016] [Accepted: 05/02/2017] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND AND AIMS Colorectal cancer (CRC) is associated with a significantly reduced survival rate in transplant recipients. The prevalence and risk factors of CRC and of colorectal polyps after orthotopic liver transplant (OLT) remain unclear. The study aim was to determine the prevalence of colorectal polyps in OLT recipients. A secondary objective was to explore possible risk factors of polyps. PATIENTS AND MATERIALS This was a retrospective single center study of all OLT recipients transplanted between 2007 and 2009. All patients who underwent a colonoscopy 5 ± 5 years after OLT were included. The outcome was colorectal polyps, as identified on colonoscopy. A logistic regression model was performed to identify potential predictors of polyps. RESULTS Of 164 OLT recipients, 80 were included in this study. Polyps were diagnosed in 37 % of patients before transplant and in 33 % afterwards. With regard to post-transplant lesions, 22 % were advanced adenomas or cancerous. In the regression analysis, the odds of post-transplant polyps were 11 times higher in patients with alcoholic liver disease (OR 11.3, 95 %CI 3.2 - 39.4; P < 0.001). CONCLUSION Patients with end-stage liver disease may be at high risk of colorectal polyps before and after liver transplant, and screening should be continued in both contexts. Those with alcoholic liver disease are particularly at risk for post-OLT polyps and may benefit from more intensive screening.
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Affiliation(s)
- Ann T. Ma
- Service de gastroentérologie et d’hépatologie, Hôpital St-Luc, Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada,Corresponding author Ann T. Ma, MD Hôpital St-LucCentre Hospitalier de l’Université de Montréal1058 Rue Saint-DenisMontréalQCCanadaH2X 3J4+1-514-412-7372
| | - Amélie Therrien
- Service de gastroentérologie et d’hépatologie, Hôpital St-Luc, Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada,Centre de Recherche, Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada
| | - Jeanne-Marie Giard
- Service de gastroentérologie et d’hépatologie, Hôpital St-Luc, Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada,Centre de Recherche, Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada
| | - Daniel von Renteln
- Service de gastroentérologie et d’hépatologie, Hôpital St-Luc, Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada,Centre de Recherche, Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada
| | - Mickael Bouin
- Service de gastroentérologie et d’hépatologie, Hôpital St-Luc, Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada,Centre de Recherche, Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada
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Abstract
Colorectal cancer (CRC) contributes a major burden of cancer mortality in the United States. There are multiple effective screening approaches that can reduce CRC mortality. These approaches are supported by different levels of evidence, and each has its own advantages and disadvantages. Implementing a systematic approach to screening that addresses the multiple steps involved in the screening process is essential to improving population-level CRC screening. Offering patients stool-based screening is important for increasing screening uptake. However, programs that offer stool testing must support the population health infrastructure needed to promote adherence to repeat testing and follow-up of abnormal tests.
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Affiliation(s)
- Alison T Brenner
- Cecil G Sheps Center for Health Services Research, University of North Carolina, 725 Martin Luther King Jr Boulevard, CB# 7590, Chapel Hill, NC 27599-7590, USA.
| | - Michael Dougherty
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, 4182 Bioinformatics Building, 130 Mason Farm Road, Chapel Hill, NC 27599-6134, USA
| | - Daniel S Reuland
- Division of General Internal Medicine, Department of Medicine, University of North Carolina, 725 Martin Luther King Jr Boulevard, CB# 7590, Chapel Hill, NC 27599-7590, USA
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Komaki Y, Komaki F, Micic D, Ido A, Sakuraba A. Risk of colorectal cancer in chronic liver diseases: a systematic review and meta-analysis. Gastrointest Endosc 2017; 86:93-104.e5. [PMID: 28011280 DOI: 10.1016/j.gie.2016.12.009] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Accepted: 12/01/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS The risk of colorectal cancer (CRC) in various chronic liver diseases compared with the general population remains unclear. We performed a systematic review and meta-analysis to assess the risk of CRC in patients with chronic liver diseases before and after liver transplantation. METHODS Electronic databases were searched for studies assessing the risk of CRC in patients with chronic liver diseases. The primary outcome was the pooled risk of CRC among studies that reported the risk as standardized incidence rate (SIR). RESULTS Fifty studies that included 55,991 patients were identified. Among studies that included hepatitis and cirrhotic patients, the pooled SIR was 2.06 (P < .0001; 95% confidence interval (CI), 1.46-2.90) with moderate heterogeneity (I2 = 49.2%), which appeared to be because of the difference between subgroup of diseases and the power of studies. Three studies reported an increased risk of CRC in primary sclerosing cholangitis patients (pooled SIR 6.70; P < .0001; 95% CI, 3.48-12.91) with moderate heterogeneity (I2 = 36.3%), which appeared to be because of the difference between the power of studies. Among studies that included post-transplant patients, the pooled SIR was 2.16 (P < .0001; 95% CI, 1.59-2.94) with moderate heterogeneity (I2 = 56.4%). Meta-regression showed a correlation between the proportion of autoimmune-related liver diseases and the risk of CRC. CONCLUSIONS Patients with chronic liver diseases had an increased risk of CRC compared with the general population, which persisted after liver transplantation. A more intensive surveillance for CRC is warranted in this population.
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Affiliation(s)
- Yuga Komaki
- Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, The University of Chicago Medicine, Chicago, Illinois, USA
| | - Fukiko Komaki
- Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, The University of Chicago Medicine, Chicago, Illinois, USA
| | - Dejan Micic
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Akio Ido
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Atsushi Sakuraba
- Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, The University of Chicago Medicine, Chicago, Illinois, USA
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Gastrointestinal Pathologies in Patients After Successful Renal Transplantation-A Pilot Study. Transplant Proc 2017; 48:1566-9. [PMID: 27496448 DOI: 10.1016/j.transproceed.2016.02.060] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2015] [Revised: 01/31/2016] [Accepted: 02/24/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND The beneficial effect of kidney transplantation in patients requiring continuous renal replacement therapy owing to chronic kidney disease is well known and accepted. Kidney transplantation protects the patient from complications that may develop during chronic dialysis. Unfortunately, there is also evidence that kidney transplant patients are more prone to developing cancer than healthy persons. The aim of this study was to evaluate the prevalence of gastrointestinal pathologies in patients after kidney transplantation. METHODS Adult patients after kidney transplantation, who are under the care of the Outpatient Department of Nephrology in Gdańsk, received alarm symptom questionnaires and referral for testing for the presence of fecal occult blood. Then, in 45 selected patients (29 men and 16 women) endoscopic examination was performed. Mean age was 57.6 ± 10.1 (range, 35-83) years. RESULTS Out of ∼940 patients after kidney transplantation, resting under supervision of outpatient department, 181 patients completed the questionnaire and 100 gave a stool sample for testing: 32 results were positive. After analyzing the questionnaires and stool results, 88 patients were qualified for further investigation. The endoscopic examination had been performed so far in 45 patients and revealed gastritis and/or duodenitis in 33 patients, diverticular colon disease in 18, esophagitis in 8, colon polyps in 14, stomach polyps in 3, inflammatory bowel disease in 7, and cancers in 3. CONCLUSIONS The preliminary results indicate that patients after kidney transplantation have significant risk of gastrointestinal pathologies and require detailed diagnostic endoscopy.
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31
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Doycheva I, Amer S, Watt KD. De Novo Malignancies After Transplantation: Risk and Surveillance Strategies. Med Clin North Am 2016; 100:551-67. [PMID: 27095645 DOI: 10.1016/j.mcna.2016.01.006] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
De novo malignancies are one of the leading causes of late mortality after liver and kidney transplantation. Nonmelanoma skin cancer is the most common malignancy, followed by posttransplant lymphoproliferative disorder and solid organ tumors. Immunosuppression is a key factor for cancer development, although many other transplant-related and traditional risk factors also play a role. In this review, the authors summarize risk factors and outcomes of frequently encountered de novo malignancies after liver and kidney transplantation to stratify recipients at highest risk. Future efforts in prospectively validated, cost-effective surveillance strategies that improve survival of these complex patients are greatly needed.
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Affiliation(s)
- Iliana Doycheva
- Division of Gastroenterology and Hepatology, Medical University-Sofia, 1 G. Sofiisky Boulevard, Sofia 1431, Bulgaria
| | - Syed Amer
- Division of Internal Medicine, Mayo Clinic, 5777 East Mayo Boulevard, Phoenix, AZ 85054, USA
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, CH-10, 200 First Street Southwest, Rochester, MN 55905, USA.
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Mukthinuthalapati PK, Gotur R, Ghabril M. Incidence, risk factors and outcomes of de novo malignancies post liver transplantation. World J Hepatol 2016; 8:533-544. [PMID: 27134701 PMCID: PMC4840159 DOI: 10.4254/wjh.v8.i12.533] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2016] [Revised: 03/08/2016] [Accepted: 04/06/2016] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) is associated with a 2 to 7 fold higher, age and gender adjusted, risk of de novo malignancy. The overall incidence of de novo malignancy post LT ranges from 2.2% to 26%, and 5 and 10 years incidence rates are estimated at 10% to 14.6% and 20% to 32%, respectively. The main risk factors for de novo malignancy include immunosuppression with impaired immunosurveillance, and a number of patient factors which include; age, latent oncogenic viral infections, tobacco and alcohol use history, and underlying liver disease. The most common cancers after LT are non-melanoma skin cancers, accounting for approximately 37% of de novo malignancies, with a noted increase in the ratio of squamous to basal cell cancers. While these types of skin cancer do not impact patient survival, post-transplant lymphoproliferative disorders and solid organ cancer, accounting for 25% and 48% of malignancies, are associated with increased mortality. Patients developing these types of cancer are diagnosed at more advanced stages, and their cancers behave more aggressively compared with the general population. Patients undergoing LT for primary sclerosing cholangitis (particularly with inflammatory bowel disease) and alcoholic liver disease have high rates of malignancies compared with patients undergoing LT for other indications. These populations are at particular risk for gastrointestinal and aerodigestive cancers respectively. Counseling smoking cessation, skin protection from sun exposure and routine clinical follow-up are the current approach in practice. There are no standardized surveillance protocol, but available data suggests that regimented surveillance strategies are needed and capable of yielding cancer diagnosis at earlier stages with better resulting survival. Evidence-based strategies are needed to guide optimal surveillance and safe minimization of immunosuppression.
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Saumoy M, Jesudian AB, Aden B, Serur D, Sundararajan S, Sivananthan G, Gambarin-Gelwan M. High prevalence of colon adenomas in end-stage kidney disease patients on hemodialysis undergoing renal transplant evaluation. Clin Transplant 2016; 30:256-62. [DOI: 10.1111/ctr.12684] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/15/2015] [Indexed: 12/30/2022]
Affiliation(s)
- Monica Saumoy
- Department of Gastroenterology; Weill Cornell Medical College; New York NY USA
| | - Arun B. Jesudian
- Department of Gastroenterology; Weill Cornell Medical College; New York NY USA
| | - Brandon Aden
- Department of Public Health; Weill Cornell Medical College; New York NY USA
| | - David Serur
- Department of Nephrology; Weill Cornell Medical College; New York NY USA
| | | | | | - Maya Gambarin-Gelwan
- Department of Gastroenterology; Memorial Sloan Kettering Cancer Center; New York NY USA
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Abstract
BACKGROUND Treatment-related immunosuppression in organ transplant recipients has been linked to increased incidence and risk of progression for several malignancies. Using a population-based cancer cohort, we evaluated whether organ transplantation was associated with worse prognosis in elderly patients with non-small cell lung cancer (NSCLC). METHODS Using the Surveillance, Epidemiology, and End Results Registry linked to Medicare claims, we identified 597 patients aged 65 years or older with NSCLC who had received organ transplants (kidney, liver, heart, or lung) before cancer diagnosis. These cases were compared to 114,410 untransplanted NSCLC patients. We compared overall survival (OS) by transplant status using Kaplan-Meier methods and Cox regression. To account for an increased risk of non-lung cancer death (competing risks) in transplant recipients, we used conditional probability function (CPF) analyses. Multiple CPF regression was used to evaluate lung cancer prognosis in organ transplant recipients while adjusting for confounders. RESULTS Transplant recipients presented with earlier stage lung cancer (P = 0.002) and were more likely to have squamous cell carcinoma (P = 0.02). Cox regression analyses showed that having received a non-lung organ transplant was associated with poorer OS (P < 0.05), whereas lung transplantation was associated with no difference in prognosis. After accounting for competing risks of death using CPF regression, no differences in cancer-specific survival were noted between non-lung transplant recipients and nontransplant patients. CONCLUSIONS Non-lung solid organ transplant recipients who developed NSCLC had worse OS than nontransplant recipients due to competing risks of death. Lung cancer-specific survival analyses suggest that NSCLC tumor behavior may be similar in these 2 groups.
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Comment on "Yield of Screening Colonoscopy in Renal Transplant Candidates". Can J Gastroenterol Hepatol 2016; 2016:5824235. [PMID: 27444237 PMCID: PMC4904692 DOI: 10.1155/2016/5824235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2015] [Accepted: 12/23/2015] [Indexed: 11/18/2022] Open
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Burra P, Rodriguez-Castro KI. Neoplastic disease after liver transplantation: Focus on de novo neoplasms. World J Gastroenterol 2015; 21:8753-8768. [PMID: 26269665 PMCID: PMC4528018 DOI: 10.3748/wjg.v21.i29.8753] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2015] [Revised: 05/31/2015] [Accepted: 07/08/2015] [Indexed: 02/06/2023] Open
Abstract
De novo neoplasms account for almost 30% of deaths 10 years after liver transplantation and are the most common cause of mortality in patients surviving at least 1 year after transplant. The risk of malignancy is two to four times higher in transplant recipients than in an age- and sex-matched population, and cancer is expected to surpass cardiovascular complications as the primary cause of death in transplanted patients within the next 2 decades. Since exposure to immunosuppression is associated with an increased frequency of developing neoplasm, long-term immunosuppression should be therefore minimized. Promising results in the prevention of hepatocellular carcinoma (HCC) recurrence have been reported with the use of mTOR inhibitors including everolimus and sirolimus and the ongoing open-label prospective randomized controlled SILVER. Study will provide more information on whether sirolimus-containing vs mTOR-inhibitor-free immunosuppression is more efficacious in reducing HCC recurrence.
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Reusser NM, Downing C, Guidry J, Tyring SK. HPV Carcinomas in Immunocompromised Patients. J Clin Med 2015; 4:260-81. [PMID: 26239127 PMCID: PMC4470124 DOI: 10.3390/jcm4020260] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Revised: 12/13/2014] [Accepted: 12/19/2014] [Indexed: 12/20/2022] Open
Abstract
Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide and can result in pre-malignancies or overt malignancies of the skin and mucosal surfaces. HPV-related illnesses are an important personal and public health problem causing physical, mental, sexual and financial detriments. Moreover, this set of malignancies severely affects the immunosuppressed population, particularly HIV-positive patients and organ-transplant recipients. There is growing incidence of HPV-associated anogenital malignancies as well as a decrease in the average age of affected patients, likely related to the rising number of high-risk individuals. Squamous cell carcinoma is the most common type of HPV-related malignancy. Current treatment options for HPV infection and subsequent disease manifestations include imiquimod, retinoids, intralesional bleomycin, and cidofovir; however, primary prevention with HPV vaccination remains the most effective strategy. This review will discuss anogenital lesions in immunocompromised patients, cutaneous warts at nongenital sites, the association of HPV with skin cancer in immunocompromised patients, warts and carcinomas in organ-transplant patients, HIV-positive patients with HPV infections, and the management of cutaneous disease in the immunocompromised patient.
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Affiliation(s)
- Nicole M Reusser
- Medical School, the University of Texas Health Science Center at Houston, 6431 Fannin, Houston, TX 77030, USA.
| | | | - Jacqueline Guidry
- Center for Clinical Studies, 1401 Binz, Suite 200, Houston, TX 77004, USA.
| | - Stephen K Tyring
- Medical School, the University of Texas Health Science Center at Houston, 1401 Binz, Suite 200, Houston, TX 77004, USA.
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Lee JT, Dunn TB, Sirany AM, Melton GB, Madoff RD, Kwaan MR. Colorectal surgery after kidney transplantation: characteristics of early vs. late posttransplant interventions. J Gastrointest Surg 2014; 18:1299-305. [PMID: 24838995 DOI: 10.1007/s11605-014-2534-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2013] [Accepted: 05/02/2014] [Indexed: 01/31/2023]
Abstract
BACKGROUND The majority of colorectal complications after kidney transplantation reportedly occur <1 year of transplant. We aimed to identify differences in complications in the early and late posttransplant period. METHODS We retrospectively reviewed kidney transplant recipients undergoing colorectal resection from 1 June 2000 to 1 June 2012 at a single institution, comparing patients by posttransplant year (<1 vs. >1 year). Measured outcomes included major complications, postoperative length of stay, perioperative mortality, reoperations, and readmissions. RESULTS We identified 45 patients aged 31-77 (median 55). Gastrointestinal malignancy (31 %), diverticular disease (24 %), and ischemic colitis (16 %) were the most common indications for surgery. The early group (n = 9) had more cases of ischemic colitis (44 vs. 6 %, p = 0.01), emergent operations (100 vs. 33 %, p = 0.0003), blood transfusion (78 vs. 31 %, p = 0.02), longer length of stay (23.2 ± 12 vs. 11.7 ± 10 days, p = 0.02), and higher mortality rate (33 vs. 6 %, p = 0.05 compared to the late group (n = 36)). There were no significant differences in major complications, reoperations, or readmissions. CONCLUSIONS Kidney transplant recipients undergoing colorectal resection <1 year of transplant have a higher incidence of emergency surgery and ischemic colitis compared with those with >1 year posttransplant. Despite these findings, patients with grafts <1 year had a similar postoperative complication rate to patients with grafts >1 year.
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Affiliation(s)
- Janet T Lee
- Division of Colon and Rectal Surgery, Department of Surgery, University of Minnesota, 420 Delaware St SE, MMC#195, Minneapolis, MN, 55455, USA,
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Sneider EB, Davids JS. Effect of chemotherapy, radiation, or immunosuppression on the integrity of the intestinal anastomosis. SEMINARS IN COLON AND RECTAL SURGERY 2014. [DOI: 10.1053/j.scrs.2014.04.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
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Merchea A, Abdelsattar ZM, Taner T, Dean PG, Colibaseanu DT, Larson DW, Dozois EJ. Outcomes of colorectal cancer arising in solid organ transplant recipients. J Gastrointest Surg 2014; 18:599-604. [PMID: 24254836 DOI: 10.1007/s11605-013-2402-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2013] [Accepted: 10/22/2013] [Indexed: 01/31/2023]
Abstract
INTRODUCTION The incidence of colorectal cancer posttransplantation is unclear. Limited reports exist and have conflicting conclusions. We aimed to review the clinical features and oncologic outcomes of colorectal cancer in transplant recipients at our institution. METHODS A retrospective review of all patients diagnosed with colorectal cancer after solid organ transplantation between 2000 and 2011 was conducted. Clinical features and outcomes were reviewed. RESULTS Twenty of 3,946 patients were identified. The most common single organ transplanted was the kidney (n = 8). Six patients had multiorgan transplantation. Median age of diagnosis of cancer was 64.3 years, and median time from transplant to diagnosis of cancer was 8.7 years. Ten patients were symptomatic at presentation. Cancer was identified on routine colonoscopy in seven patients. Tumors were most commonly found in the right colon (n = 14, 70%). Six patients had stage IV disease at presentation. Short-term morbidity was identified in 11 patients. Postoperative mortality occurred in one patient. Median follow-up was 2.47 years. Overall survival at 5 years was 69%, and disease-free survival was 68 %. Distant recurrence was seen in 3 (15%) patients. CONCLUSION Colorectal cancer in these patients is rare, and surgery can be done safely. Vigilant screening must be maintained in this patient population.
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Affiliation(s)
- Amit Merchea
- Section of Colon and Rectal Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32256, USA,
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41
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Verran DJ, Mulhearn MH, Dilworth PJ, Balderson GA, Munn S, Chen JW, Fink MA, Crawford MD, McCaughan GW. Nature and outcomes of the increased incidence of colorectal malignancy after liver transplantation in Australasia. Med J Aust 2014; 199:610-2. [PMID: 24182227 DOI: 10.5694/mja13.10102] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2013] [Accepted: 06/16/2013] [Indexed: 12/19/2022]
Abstract
OBJECTIVES To examine whether incidence of colorectal malignancy is increased in Australasian liver transplant recipients compared with the general population of Australia, and to assess the characteristics and outcomes of colorectal malignancy in this patient group. DESIGN, SETTING AND PATIENTS Data on patients who underwent orthotopic liver transplantation (OLTx) and had a diagnosis of de-novo colorectal malignancy after transplantation during the period 1985-2011 were obtained from the Australia and New Zealand Liver Transplant Registry, and these data were compared with colorectal malignancy data from the Australian Institute of Health and Welfare. MAIN OUTCOME MEASURES Time from OLTx to diagnosis of colorectal malignancy, stage of colorectal malignancy at diagnosis, patient survival, and standardised incidence ratio (SIR) for colorectal malignancy. RESULTS Forty-eight of 3735 recipients (1.3%) were diagnosed with colorectal malignancy at a median of 7.3 years after OLTx. More advanced colorectal malignancy (regional or metastatic disease) was evident at diagnosis in 20 of the 48 patients; these patients tended to be younger than patients with less advanced malignancy (P = 0.01) and diagnosed sooner after OLTx (P = 0.005). Despite treatment predominantly with surgery, 19 of the 48 patients died from the malignancy. The overall SIR for colorectal malignancy liver transplant recipients compared with the general population of Australia was 2.80 (95% CI, 2.06-3.71). CONCLUSIONS The incidence of colorectal malignancy is increased in liver transplant recipients in comparison with the general population. Of concern is the tendency for advanced malignancy to be diagnosed in younger patients. These data highlight the importance of considering whether specific guidelines for colorectal malignancy screening in the Australasian adult liver transplant population are needed.
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Affiliation(s)
- Deborah J Verran
- Transplantation Services, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
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Singh S, Varayil JE, Loftus EV, Talwalkar JA. Incidence of colorectal cancer after liver transplantation for primary sclerosing cholangitis: a systematic review and meta-analysis. Liver Transpl 2013; 19:1361-9. [PMID: 24019127 DOI: 10.1002/lt.23741] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2013] [Revised: 08/08/2013] [Accepted: 08/27/2013] [Indexed: 12/15/2022]
Abstract
Patients with primary sclerosing cholangitis (PSC) and associated inflammatory bowel disease (IBD) have an increased risk of colorectal cancer (CRC). We estimated the pooled incidence of CRC after liver transplantation (LT) in patients with PSC as well as in a subset of patients with associated IBD (PSC-IBD). Through a systematic review of major bibliographic databases up to April 1, 2013, we identified cohort studies reporting the incidence of de novo CRC after LT for PSC. The main outcome measure was CRC incidence rate (IR) per 1000 person-years after LT in all patients with PSC and in a subset of patients with PSC-IBD with an intact colon. According to a meta-analysis of 18 independent cohorts (69 cases of CRC among 1987 patients), the pooled IR of de novo CRC in patients with PSC after LT was 5.8 per 1000 person-years [95% confidence interval (CI) = 3.8-7.8]. According to a meta-analysis of 16 independent cohort studies (66 cases of CRC among 1017 patients), the IR of CRC in patients with PSC-IBD and an intact colon at the time of LT was 13.5 per 1000 person-years (95% CI = 8.7-18.2). A long duration of IBD and extensive colitis were identified as risk factors for CRC. Specific transplant-related factors that can increase the risk of CRC have not been identified. In conclusion, the risk of CRC remains high for patients who undergo LT for PSC, particularly in the subset of patients with associated IBD and an intact colon at the time of LT. Aggressive colonoscopic surveillance for CRC would be prudent for patients with PSC-IBD even after LT.
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Affiliation(s)
- Siddharth Singh
- Division of Gastroenterology and Hepatology; Mayo Clinic; Rochester MN
| | | | - Edward V. Loftus
- Division of Gastroenterology and Hepatology; Mayo Clinic; Rochester MN
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Pant C, Deshpande A, Larson A, O'Connor J, Rolston DDK, Sferra TJ. Diarrhea in solid-organ transplant recipients: a review of the evidence. Curr Med Res Opin 2013; 29:1315-28. [PMID: 23777312 DOI: 10.1185/03007995.2013.816278] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVE To provide a comprehensive review of the literature as it relates to diarrhea in solid organ transplant (SOT) recipients. In this article, we review the epidemiology, pathogenesis, clinical manifestations, diagnosis and management of diarrhea in SOT recipients and discuss recent advances and challenges. METHODS Two investigators conducted independent literature searches using PubMed, Web of Science, and Scopus until January 1st, 2013. All databases were searched using a combination of the terms diarrhea, solid organ transplant, SOT, transplant associated diarrhea, and transplant recipients. Articles that discussed diarrhea in SOT recipients were reviewed and relevant cross-references also read and evaluated for inclusion. Selection bias could be a possible limitation of the approach used in selecting or finding articles for this article. FINDINGS Post-transplant diarrhea is a common and distressing occurrence in patients, which can have significant deleterious effects on the clinical course and well-being of the organ recipient. A majority of cases are due to infectious and drug-related etiologies. However, various other etiologies including inflammatory bowel disease must be considered in the differential diagnosis. A step-wise, informed approach to post-transplant diarrhea will help the clinician achieve the best diagnostic yield. The use of diagnostic endoscopy should be preceded by exclusion of an infectious or drug-related cause of diarrhea. Empiric management with antidiarrheal agents, probiotics, and lactose-free diets may have a role in managing patients for whom no cause can be determined even after an extensive investigation. CONCLUSIONS Physicians should be familiar with the common etiologies that result in post-transplant diarrhea. A directed approach to diagnosis and treatment will not only help to resolve the diarrhea but also prevent potentially life-threatening consequences including loss of the graft as well. Prospective studies are required to determine the etiology of post-transplant diarrhea in different clinical and geographic settings.
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Affiliation(s)
- Chaitanya Pant
- University of Oklahoma Health Sciences Center , Oklahoma City, OK , USA
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44
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Singh S, Loftus EV, Talwalkar JA. Inflammatory bowel disease after liver transplantation for primary sclerosing cholangitis. Am J Gastroenterol 2013; 108:1417-25. [PMID: 23896954 DOI: 10.1038/ajg.2013.163] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2013] [Accepted: 04/23/2013] [Indexed: 02/07/2023]
Abstract
The course of inflammatory bowel disease (IBD) after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is complex, with several IBD-, PSC-, and transplant-related factors interplaying with each other. Approximately one-third of patients with known IBD improve, and one-third paradoxically worsen, after LT for PSC. Active IBD, discontinuation of 5-aminosalicylates (5-ASA) at time of LT and tacrolimus-based immunosuppression may be associated with an unfavorable course of IBD after LT. Approximately 14-30% patients with PSC may develop de novo IBD 10 years after LT. LT confers a high risk of pouchitis after ileal pouch-anal anastomosis, although it may not be higher than baseline rates for PSC patients. The risk of colorectal cancer continues to be high after LT for PSC, and is higher in this cohort of patients with PSC-IBD, compared with patients undergoing LT for other indications. IBD does not adversely affect patient survival after LT, although the risk of recurrent PSC in the allograft may be higher in patients with IBD and an intact colon at time of LT. Standard therapy with 5-ASA and/or azathioprine may be appropriate for treatment of active IBD after LT and maintenance of remission. Anti-tumor necrosis factor-α agents are effective, but should be used with caution because of high risk of adverse events. The management of IBD after LT requires close coordination between transplant hepatologists and IBD experts.
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Affiliation(s)
- Siddharth Singh
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
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Connolly K, Manders P, Earls P, Epstein RJ. Papillomavirus-associated squamous skin cancers following transplant immunosuppression: one Notch closer to control. Cancer Treat Rev 2013; 40:205-14. [PMID: 24051018 DOI: 10.1016/j.ctrv.2013.08.005] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2013] [Revised: 07/06/2013] [Accepted: 08/13/2013] [Indexed: 12/12/2022]
Abstract
The frequent occurrence of cutaneous squamous cell carcinomas (SCCs) containing weakly tumorigenic human papillomaviruses (HPVs) following iatrogenic immunosuppression for organ transplantation remains incompletely understood. Here we address this problem in the light of recent insights into (1) the association of low-risk β-HPVs with skin SCCs in the rare genetic syndromes of epidermodysplasia verruciformis and xeroderma pigmentosum, (2) the frequent recovery of post-transplant tumor control on substituting calcineurin-inhibitory with mTOR-inhibitory immunosuppression, (3) the unexpectedly favorable prognosis of node-positive SCCs containing high-risk α-HPVs originating in the activated immune niche of the oropharynx, (4) the rapid occurrence of HPV-negative SCCs in ultraviolet (UV)-damaged skin of melanoma patients receiving Raf-inhibitory drugs, and (5) the selective ability of β-HPV E6 oncoproteins to inhibit Notch tumor-suppressive signaling in cutaneous and mesenchymal tissues. The crosstalk so implied between oncogenic UV-induced mutations, defective host immunity, and β-HPV-dependent stromal-epithelial signaling suggests that immunosuppressants such as calcineurin inhibitors intensify mitogenic signalling in TP53-mutant keratinocytes while also abrogating immune-dependent Notch-mediated tumor repression. This emerging interplay between solar damage, viral homeostasis and immune control makes it timely to reappraise strategies for managing skin SCCs in transplant patients.
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Affiliation(s)
- Kate Connolly
- Department of Oncology, St. Vincent's Hospital, The Kinghorn Cancer Centre, UNSW Clinical School, Sydney, Australia
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Liang YM, Guan JZ, Li N. Diagnosis and treatment of rectal or anal carcinoma after renal transplantation. Shijie Huaren Xiaohua Zazhi 2013; 21:1893-1898. [DOI: 10.11569/wcjd.v21.i19.1893] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To report a case of rectal adenocarcinoma and a case of anal squamous cell carcinoma in situ after renal transplantation, and review the relevant literature.
METHODS: A case of squamous cell carcinoma in situ arising in a patient 2 years after renal transplantation and a case of rectal adenocarcinoma arising in a patient 14 years after renal transplantation were collected. The resected specimens were fixed in buffered formalin, paraffin-embedded, 4 μm-sectioned, and reviewed by two pathologists. Human papillary virus (HPV) and Epstein-Barr virus (EBV) were detected both in the adenocarcinoma and squamous carcinoma. K-ras and BRAF genes were sequenced in rectal adenocarcinoma to identify mutations.
RESULTS: The patient suffering from squamous cell carcinoma in situ was a 54-year-old female, with a history of mixed hemorrhoid for 30 years without obvious bleeding. The regimen of mycophenolate mofetil (MMF), prednisone (Pred) and tacrolimus was used to control rejection reactions. Six months after transplantation, the patients complained of intermittent painless hemorrhage. The diagnosis of mixed hemorrhoid was made by colonoscopy and conservative treatment was performed consequently for the next year. Since the hemorrhage became worse in the last month, hemorrhoid resection was performed. Squamous carcinoma in situ was diagnosed. There was no HPV or EBV infection. No adverse events occurred in the next 36-mo follow-up period. The patient suffering from rectal adenocarcinoma was a 39-year old male who complained of bloody stools for one year and aggravation for 1 mo. Colonoscopy revealed a space-occupying lesion localized in the rectum. He was diagnosed with renal failure 15 years ago and accepted renal allograft 14 years ago. MMF and Pred were used as the immunosuppressant for 12 years and stopped as the allograft lost its function 2 years ago. Anterior resection was performed and pathologic examination revealed poorly differentiated adenocarcinoma mixed with mucinous adenocarcinoma accompanied with numerous cancerous emboli and lymph node metastasis (pT3N2aM0). After 18 mo of follow-up, he suffered from abdominal relapse and hepatic metastasis. The lymphocytes infiltrating into the carcinoma were negative for EBER. Wild-type K-ras and BRAF were detected.
CONCLUSION: Bloody stools can be the fist sign of anal or rectal carcinoma. Immunosuppressive drugs may act as a pivotal enhancer during the pathogenesis of carcinoma. The patients sensitive to immunosuppression therapy and/or undergoing long-term immunosuppression therapy should be cautious of carcinoma.
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Koudougou C, Bonneville M, Matysiak-Budnik T, Touchefeu Y. Review article: antitumoural immunity in colorectal cancer - current and potential future implications in clinical practice. Aliment Pharmacol Ther 2013; 38:3-15. [PMID: 23692025 DOI: 10.1111/apt.12337] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2013] [Revised: 02/21/2013] [Accepted: 04/29/2013] [Indexed: 12/22/2022]
Abstract
BACKGROUND Most of the current research in gastrointestinal oncology is focused on biology of cancer itself, but there is growing interest in the patient's immune system response and its relation with cancer cells. AIM To review the impact of the antitumoural immune response on epidemiology, prognosis and treatment of colorectal cancer. METHODS Search of the literature published in English using the PubMed database. RESULTS The role of the immune system in the antitumoural immunosurveillance is clearly supported by the increased incidence of colorectal cancer and adenomatous polyps in immunosuppressed patients. Moreover, the degree of infiltration of the tumours by the immune cells has been shown to be a strong prognostic factor of both disease recurrence and survival. The immune system plays an important role in the chemotherapy-induced cell death. New therapeutic strategies targeting the antitumoural immunity are being currently investigated with promising results. CONCLUSION Better knowledge of antitumoural immune system can have a major impact on patients' management in daily clinical practice. Colorectal cancer screening is an important issue in immunosuppressed patients, and recommendations should be refined for selected high-risk patients. The use of an immune score to guide the therapeutic strategies in the adjuvant setting should be supported. Further and larger clinical trials are necessary to accelerate the development of innovative immune therapies.
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Affiliation(s)
- C Koudougou
- Institut des Maladies de l'Appareil Digestif & Digestive Oncology Unit, CHU de Nantes, Nantes Cedex, France
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Collins MG, Teo E, Cole SR, Chan CY, McDonald SP, Russ GR, Young GP, Bampton PA, Coates PT. Screening for colorectal cancer and advanced colorectal neoplasia in kidney transplant recipients: cross sectional prevalence and diagnostic accuracy study of faecal immunochemical testing for haemoglobin and colonoscopy. BMJ 2012; 345:e4657. [PMID: 22833618 PMCID: PMC3404596 DOI: 10.1136/bmj.e4657] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To investigate whether screening kidney transplant recipients aged over 50 years for colorectal cancer with a faecal immunochemical test for haemoglobin might be justified, by determining the prevalence of advanced colorectal neoplasia and evaluating the diagnostic accuracy of faecal haemoglobin testing compared with colonoscopy in a population of kidney transplant recipients at otherwise average risk. DESIGN Cross sectional prevalence and diagnostic accuracy study with index test of faecal haemoglobin and reference standard of colonoscopy. SETTING Outpatient clinics in metropolitan and regional hospitals in South Australia. PARTICIPANTS 229 kidney transplant recipients aged 50 years and over, who were at least 6 months (mean 9.0 (SD 8.4) years) post-transplant and otherwise at average risk of colorectal cancer, completed the study between June 2008 and October 2011. INTERVENTIONS Faecal immunochemical testing (Enterix Insure) for human haemoglobin, followed by colonoscopy with histological evaluation of retrieved samples. MAIN OUTCOME MEASURES Prevalence of advanced colorectal neoplasia, defined as an adenoma at least 10 mm in diameter, villous features, high grade dysplasia, or colorectal cancer; sensitivity, specificity, and predictive values of faecal haemoglobin testing for advanced neoplasia compared with colonoscopy. RESULTS Advanced colorectal neoplasia was found in 29 (13%, 95% confidence interval 9% to 18%) participants, including 2% (n=4) with high grade dysplasia and 2% (n=5) with colorectal cancer. Faecal testing for haemoglobin was positive in 12% (n=28); sensitivity, specificity, and positive and negative predictive values for advanced neoplasia were 31.0% (15.3% to 50.8%), 90.5% (85.6% to 94.2%), 32.1% (15.9% to 52.4%), and 90.1% (85.1% to 93.8%). Colonoscopy was well tolerated, with no significant adverse outcomes. To identify one case of advanced neoplasia, 8 (6 to 12) colonoscopies were needed. CONCLUSIONS Kidney transplant recipients aged over 50 years have a high prevalence of advanced colorectal neoplasia. Faecal haemoglobin screening for colorectal neoplasia has similar performance characteristics in transplant recipients to those reported in general population studies, with poor sensitivity but reasonable specificity. Surveillance colonoscopy might be a more appropriate approach in this population. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry ACTRN12608000154303.
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Affiliation(s)
- Michael G Collins
- Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, SA 5000, Australia
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Kazama S, Hongo K, Sunami E, Sugawara Y, Kokudo N, Kitayama J. Six Cases of Primary Colorectal Cancer After Living-donor Liver Transplantation: A Single-institution Experience in Japan. Jpn J Clin Oncol 2012; 42:586-90. [DOI: 10.1093/jjco/hys073] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
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Parnaby CN, Barrow EJ, Edirimanne SB, Parrott NR, Frizelle FA, Watson AJM. Colorectal complications of end-stage renal failure and renal transplantation: a review. Colorectal Dis 2012; 14:403-15. [PMID: 22493792 DOI: 10.1111/j.1463-1318.2010.02491.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM End-stage renal failure (ESRF) and renal transplant recipients are thought to be associated with an increased risk of colorectal complications. METHOD A review of the literature was performed to assess the prevalence and outcome in both benign and malignant colorectal disease. RESULTS No prospective randomized studies assessing colorectal complications in ESRF or renal transplant were identified. Case series and case reports have described the incidence and management of benign colorectal complications. Complications included diverticulitis,infective colitis, colonic bleeding and colonic perforation. There was insufficient evidence to associated iverticular disease with adult polycystic kidney disease.Three population-based studies have shown up to a twofold increased incidence of colonic cancer but not rectal cancer for renal transplant recipients. Bowel cancer screening (as per the general population) by faecal occult blood testing appears justified for renal transplant patients; however, evidence suggests that consideration of starting screening at a younger age may be worthwhile because of an increased risk of developing colonic cancer.Two population-based studies have shown a threefold and 10-fold increased incidence of anal cancer for renal transplant recipients. A single case–control study demonstrated significant increased prevalence of anal human papilloma virus (HPV) and intraepithelial neoplasia (AIN)in patients with established renal transplants. CONCLUSIONS Despite the lack of high-level evidence,ESRF and renal transplantation were associated with colorectal complications that could result in major morbidity and mortality. Bowel cancer screening in this patient group appears justified. The effectiveness of screening for HPV, AIN and anal cancer in renal transplant recipients remains unclear.
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Affiliation(s)
- C N Parnaby
- Department of Surgery, Raigmore Hospital, Inverness, UK.
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