J Gastrointest Surg (2014) 18:599–604 DOI 10.1007/s11605-013-2402-3
ORIGINAL ARTICLE
Outcomes of Colorectal Cancer Arising in Solid Organ Transplant Recipients Amit Merchea & Zaid M. Abdelsattar & Timucin Taner & Patrick G. Dean & Dorin T. Colibaseanu & David W. Larson & Eric J. Dozois
Received: 7 August 2013 / Accepted: 22 October 2013 / Published online: 20 November 2013 # 2013 The Society for Surgery of the Alimentary Tract
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 followup 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. Keywords Colorectal cancer . Transplant . Transplantation . Screening
A. Merchea (*) : D. T. Colibaseanu Section of Colon and Rectal Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32256, USA e-mail: [email protected] Z. M. Abdelsattar Department of Surgery, Mayo Clinic, Rochester, MN, USA T. Taner : P. G. Dean Division of Transplantation Surgery, Mayo Clinic, Rochester, MN, USA D. W. Larson : E. J. Dozois Division of Colon and Rectal Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA E. J. Dozois e-mail: [email protected]
Introduction Long-term survival after solid organ transplant has been associated with an increased risk of development of various de novo malignancies.1,2 This has been previously documented with non-melanomatous skin cancers and lymphoproliferative disorders.3,4 Limited and conflicting data exist regarding the risk, features, and outcomes of colorectal cancer in solid organ transplant patients. Some authors have described an equivalent risk of cancer in transplant and non-transplant populations, while others have demonstrated a trend toward an increased incidence of advanced polyps and colorectal carcinoma.5–8 These are largely based on combined registry data instead of single-institution reports. The necessary immunocompromised state of transplant recipients may impart an increased risk of colorectal adenoma and/or cancer. Immunosuppression decreases immunosurveillance and may increase the risk of development of malignancy—either through reactivation of oncogenic viruses (Epstein–Barr virus, cytomegalovirus, or JC virus) or through the inhibition of other immune mechanisms to combat
600
neoplasia.9,10 The aim of this study was to review the clinical presentation, morbidity, and oncologic outcomes in solid organ transplant recipients who developed colorectal cancer at our institution and to describe the operative treatment and outcomes, perioperative morbidity, recurrence, and survival.
Materials and Methods After receiving institutional review board approval, a retrospective review was undertaken of all patients diagnosed with colorectal adenocarcinoma after solid organ transplantation between January 1, 2000 and December 31, 2011. Patients were identified by searching the surgical procedure and transplant databases of our institution for all patients with a diagnosis of colorectal cancer occurring after solid organ transplantation (heart, lung, kidney, liver, and pancreas). Inclusion criteria included age greater than 18 years and pathologically confirmed colorectal adenocarcinoma occurring after transplantation. Patients who underwent both emergent and elective operations were included. Patients with cancer prior to transplantation were excluded. Patient records were reviewed for demographic features, operative approaches and outcomes, and vital status at last follow-up. The operating surgeon determined the type of operative procedure performed. Short-term (30 days) morbidity was described according to the Clavien grading system,11 and overall recurrence was reported. Overall survival (OS) and disease-free survival (DFS) were calculated from the date of surgery to the date of death from all causes, inclusive of postoperative deaths. OS and DFS were estimated at 1 and 5 years by use of the Kaplan–Meier method. Descriptive statistics are reported as a percentage of the total and continuous variables as the median and range.
Results Twenty of 3,946 (incidence=0.5 %) solid organ transplant recipients were identified as having developed colorectal cancer after transplantation during the study period. Ten (50 %) patients were males. Median age at diagnosis of cancer was 64.3 years (range, 49–83 years). Median time from transplant to diagnosis of cancer was 8.7 years (range, 0.4–19 years). One patient was diagnosed with cancer less than 1 year following transplant. Excluding this patient, median time from transplant to diagnosis of cancer was 10.4 years (range, 1.6–19 years). Median followup was 2.5 years (mean, 3.23 years; range, 0.02–8.8 years). Twenty-seven organs were ultimately transplanted into the 20 patients (Table 1). Fourteen patients had a single-organ transplanted. Two patients underwent concurrent multiorgan transplant. Five patients underwent a metachronous multiorgan transplant. The most commonly transplanted organ was the kidney (n =14, 52 %), followed by the liver (n =6, 22 %).
J Gastrointest Surg (2014) 18:599–604 Table 1 Distribution of transplanted organs Organ transplanted
Number of patients
Kidney Liver Heart Lung Liver + kidney Liver (1987, 1991), kidney (2001, 2003) Heart + lung (2002), kidney (2003) Heart (1991, 2002), kidney (2005, 2006)
8 3 2 1 1 2 1 2
Indications for transplantation are reported in Table 2. All patients were maintained on appropriate posttransplant immunosuppression consisting of some combination of prednisone, an antimetabolite (mycophenolate mofetil or azathioprine), and either a calcineurin-inhibitor (tacrolimus or cyclosporin) or sirolimus. Perioperative immunosuppression was administered by the transplant team, and accurate dosing was based on blood levels. Due to the significant risk of impaired wound healing, all patients with an immunosuppressive regimen that included sirolimus were switched to tacrolimus 6 weeks preoperatively. Otherwise, immunosuppressive levels were not altered once malignancy was diagnosed. Seven (35 %) patients were Epstein–Barr virus (EBV) positive, and five (25 %) were cytomegalovirus (CMV) positive. Seven (35 %) patients had also developed a noncolorectal malignancy (five non-melanomatous skin cancers, one anaplastic lymphoma, one pancreatic adenocarcinoma). Ten (50 %) patients underwent pre-transplant screening colonoscopy, nine (45 %) underwent colonoscopy after their transplant operation, and one (5 %) patient refused endoscopic examination of their colon. Of the patients who had pretransplant colonoscopy, five had normal colonoscopic examinations (no polyps found), two patients had a single 50 years for average risk screening). Four patients in our series were over the age of 50 and did not receive a pre-transplant colonoscopy. Three of these four, however, had significant comorbidities preventing this screening modality as they were awaiting cardiac transplantation. Excluding the patient who refused all endoscopic evaluation, only one patient did not undergo appropriate pre-transplant screening that should have. Furthermore, some patients in this cohort underwent transplantation before the era in which consensus colonic surveillance recommendations were in existence. It was not until the late 1990s that such recommendations emerged.18,19 In spite of the fact that our study did not demonstrate a short interval from transplantation to the development of cancer, it must be considered that an earlier and more aggressive colonoscopic surveillance program should be instituted for this high-risk population. In addition, the majority of patients were found to have right-sided tumors—as such, it is imperative that a complete colonoscopic screening evaluation rather than a limited sigmoidoscopic evaluation be conducted, regardless of patient age. The limitations of our study include the retrospective design and a potentially underpowered analysis given the small sample size. However, given that our study is singleinstitution data, we are able to describe more thoroughly the operative management and outcomes of our patients and the standardized approach in which they are generally cared for.
Conclusions Based on review of our transplant population, colorectal cancer arising de novo after solid organ transplantation does not seem to be elevated over the non-transplant population. Operative morbidity is high, but generally minor, and survival appears congruent with previously reported data regarding the general population. Vigilance and
603
appropriate screening by full colonoscopic evaluation must be maintained in this patient population, as some will not be symptomatic upon presentation.
Conflict of Interest The authors have no disclosures.
References 1. Penn I, Hammond W, Brettschneider L, Starzl TE. Malignant lymphomas in transplantation patients. Transplantation proceedings. 1969 Mar;1(1):106–12. 2. Oo YH, Gunson BK, Lancashire RJ, Cheng KK, Neuberger JM. Incidence of cancers following orthotopic liver transplantation in a single center: comparison with national cancer incidence rates for England and Wales. Transplantation. 2005 Sep 27;80(6):759–64. 3. Haagsma EB, Hagens VE, Schaapveld M, van den Berg AP, de Vries EG, Klompmaker IJ, et al. Increased cancer risk after liver transplantation: a population-based study. Journal of hepatology. 2001 Jan;34(1):84–91. 4. Penn I. Posttransplantation de novo tumors in liver allograft recipients. Liver transplantation and surgery : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 1996 Jan;2(1):52–9. 5. Rudraraju M, Osowo AT, Singh V, Carey EJ. Do patients need more frequent colonoscopic surveillance after liver transplantation? Transplantation proceedings. 2008 Jun;40(5):1522–4. 6. Silva MA, Jambulingam PS, Mirza DF. Colorectal cancer after orthotopic liver transplantation. Critical reviews in oncology/ hematology. 2005 Oct;56(1):147–53. 7. Johnson EE, Leverson GE, Pirsch JD, Heise CP. A 30-year analysis of colorectal adenocarcinoma in transplant recipients and proposal for altered screening. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 2007 Mar;11(3):272–9. 8. Atassi T, Thuluvath PJ. Risk of colorectal adenoma in liver transplant recipients compared to immunocompetent control population undergoing routine screening colonoscopy. Journal of clinical gastroenterology. 2003 Jul;37(1):72–3. 9. Selgrad M, Koornstra JJ, Fini L, Blom M, Huang R, Devol EB, et al. (2008 Oct) JC virus infection in colorectal neoplasia that develops after liver transplantation. Clin Cancer Res 14(20):6717–21. [Comparative Study Research Support, N.I.H., Extramural]. 10. Waldner M, Schimanski CC, Neurath MF. Colon cancer and the immune system: the role of tumor invading T cells. World J Gastroenterol. [Editorial Review]. 2006 Dec 7;12(45):7233–8. 11. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Annals of surgery. 2004 Aug;240(2):205–13. 12. Adami J, Gabel H, Lindelof B, Ekstrom K, Rydh B, Glimelius B, et al. Cancer risk following organ transplantation: a nationwide cohort study in Sweden. British journal of cancer. 2003 Oct 6;89(7):1221–7. 13. Kyllonen L, Salmela K, Pukkala E. Cancer incidence in a kidneytransplanted population. Transplant international : official journal of the European Society for Organ Transplantation. 2000;13 Suppl 1: S394-8. 14. Brunner FP, Landais P, Selwood NH. Malignancies after renal transplantation: the EDTA-ERA registry experience. European Dialysis and Transplantation Association-European Renal Association. Nephrology, dialysis, transplantation : official publication of the
604 European Dialysis and Transplant Association - European Renal Association. 1995;10 Suppl 1:74–80. 15. Stewart T, Henderson R, Grayson H, Opelz G. Reduced incidence of rectal cancer, compared to gastric and colonic cancer, in a population of 73,076 men and women chronically immunosuppressed. Clinical cancer research : an official journal of the American Association for Cancer Research. 1997 Jan;3(1):51–5. 16. Buell JF, Papaconstantinou HT, Skalow B, Hanaway MJ, Alloway RR, Woodle ES. De novo colorectal cancer: five-year survival is markedly lower in transplant recipients compared with the general population. Transplantation proceedings. 2005 Mar;37(2):960–1.
J Gastrointest Surg (2014) 18:599–604 17. Papaconstantinou HT, Sklow B, Hanaway MJ, Gross TG, Beebe TM, Trofe J, et al. Characteristics and survival patterns of solid organ transplant patients developing de novo colon and rectal cancer. Diseases of the colon and rectum. 2004 Nov;47(11):1898–903. 18. Winawer SJ, Fletcher RH, Miller L, Godlee F, Stolar MH, Mulrow CD, et al. Colorectal cancer screening: Clinical guidelines and rationale. Gastroenterology. 1997;(112):594–642. 19. Winawer SJ, Fletcher RH, Rex D, Bond J, Burt R, Ferrucci J, et al. Colorectal cancer screening and surveillance: Clinical guidelines and rational - Update based on new evidence. Gastroenterology. 2003;(124):544–560.
ORIGINAL ARTICLE
Outcomes of Colorectal Cancer Arising in Solid Organ Transplant Recipients Amit Merchea & Zaid M. Abdelsattar & Timucin Taner & Patrick G. Dean & Dorin T. Colibaseanu & David W. Larson & Eric J. Dozois
Received: 7 August 2013 / Accepted: 22 October 2013 / Published online: 20 November 2013 # 2013 The Society for Surgery of the Alimentary Tract
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 followup 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. Keywords Colorectal cancer . Transplant . Transplantation . Screening
A. Merchea (*) : D. T. Colibaseanu Section of Colon and Rectal Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32256, USA e-mail: [email protected] Z. M. Abdelsattar Department of Surgery, Mayo Clinic, Rochester, MN, USA T. Taner : P. G. Dean Division of Transplantation Surgery, Mayo Clinic, Rochester, MN, USA D. W. Larson : E. J. Dozois Division of Colon and Rectal Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA E. J. Dozois e-mail: [email protected]
Introduction Long-term survival after solid organ transplant has been associated with an increased risk of development of various de novo malignancies.1,2 This has been previously documented with non-melanomatous skin cancers and lymphoproliferative disorders.3,4 Limited and conflicting data exist regarding the risk, features, and outcomes of colorectal cancer in solid organ transplant patients. Some authors have described an equivalent risk of cancer in transplant and non-transplant populations, while others have demonstrated a trend toward an increased incidence of advanced polyps and colorectal carcinoma.5–8 These are largely based on combined registry data instead of single-institution reports. The necessary immunocompromised state of transplant recipients may impart an increased risk of colorectal adenoma and/or cancer. Immunosuppression decreases immunosurveillance and may increase the risk of development of malignancy—either through reactivation of oncogenic viruses (Epstein–Barr virus, cytomegalovirus, or JC virus) or through the inhibition of other immune mechanisms to combat
600
neoplasia.9,10 The aim of this study was to review the clinical presentation, morbidity, and oncologic outcomes in solid organ transplant recipients who developed colorectal cancer at our institution and to describe the operative treatment and outcomes, perioperative morbidity, recurrence, and survival.
Materials and Methods After receiving institutional review board approval, a retrospective review was undertaken of all patients diagnosed with colorectal adenocarcinoma after solid organ transplantation between January 1, 2000 and December 31, 2011. Patients were identified by searching the surgical procedure and transplant databases of our institution for all patients with a diagnosis of colorectal cancer occurring after solid organ transplantation (heart, lung, kidney, liver, and pancreas). Inclusion criteria included age greater than 18 years and pathologically confirmed colorectal adenocarcinoma occurring after transplantation. Patients who underwent both emergent and elective operations were included. Patients with cancer prior to transplantation were excluded. Patient records were reviewed for demographic features, operative approaches and outcomes, and vital status at last follow-up. The operating surgeon determined the type of operative procedure performed. Short-term (30 days) morbidity was described according to the Clavien grading system,11 and overall recurrence was reported. Overall survival (OS) and disease-free survival (DFS) were calculated from the date of surgery to the date of death from all causes, inclusive of postoperative deaths. OS and DFS were estimated at 1 and 5 years by use of the Kaplan–Meier method. Descriptive statistics are reported as a percentage of the total and continuous variables as the median and range.
Results Twenty of 3,946 (incidence=0.5 %) solid organ transplant recipients were identified as having developed colorectal cancer after transplantation during the study period. Ten (50 %) patients were males. Median age at diagnosis of cancer was 64.3 years (range, 49–83 years). Median time from transplant to diagnosis of cancer was 8.7 years (range, 0.4–19 years). One patient was diagnosed with cancer less than 1 year following transplant. Excluding this patient, median time from transplant to diagnosis of cancer was 10.4 years (range, 1.6–19 years). Median followup was 2.5 years (mean, 3.23 years; range, 0.02–8.8 years). Twenty-seven organs were ultimately transplanted into the 20 patients (Table 1). Fourteen patients had a single-organ transplanted. Two patients underwent concurrent multiorgan transplant. Five patients underwent a metachronous multiorgan transplant. The most commonly transplanted organ was the kidney (n =14, 52 %), followed by the liver (n =6, 22 %).
J Gastrointest Surg (2014) 18:599–604 Table 1 Distribution of transplanted organs Organ transplanted
Number of patients
Kidney Liver Heart Lung Liver + kidney Liver (1987, 1991), kidney (2001, 2003) Heart + lung (2002), kidney (2003) Heart (1991, 2002), kidney (2005, 2006)
8 3 2 1 1 2 1 2
Indications for transplantation are reported in Table 2. All patients were maintained on appropriate posttransplant immunosuppression consisting of some combination of prednisone, an antimetabolite (mycophenolate mofetil or azathioprine), and either a calcineurin-inhibitor (tacrolimus or cyclosporin) or sirolimus. Perioperative immunosuppression was administered by the transplant team, and accurate dosing was based on blood levels. Due to the significant risk of impaired wound healing, all patients with an immunosuppressive regimen that included sirolimus were switched to tacrolimus 6 weeks preoperatively. Otherwise, immunosuppressive levels were not altered once malignancy was diagnosed. Seven (35 %) patients were Epstein–Barr virus (EBV) positive, and five (25 %) were cytomegalovirus (CMV) positive. Seven (35 %) patients had also developed a noncolorectal malignancy (five non-melanomatous skin cancers, one anaplastic lymphoma, one pancreatic adenocarcinoma). Ten (50 %) patients underwent pre-transplant screening colonoscopy, nine (45 %) underwent colonoscopy after their transplant operation, and one (5 %) patient refused endoscopic examination of their colon. Of the patients who had pretransplant colonoscopy, five had normal colonoscopic examinations (no polyps found), two patients had a single 50 years for average risk screening). Four patients in our series were over the age of 50 and did not receive a pre-transplant colonoscopy. Three of these four, however, had significant comorbidities preventing this screening modality as they were awaiting cardiac transplantation. Excluding the patient who refused all endoscopic evaluation, only one patient did not undergo appropriate pre-transplant screening that should have. Furthermore, some patients in this cohort underwent transplantation before the era in which consensus colonic surveillance recommendations were in existence. It was not until the late 1990s that such recommendations emerged.18,19 In spite of the fact that our study did not demonstrate a short interval from transplantation to the development of cancer, it must be considered that an earlier and more aggressive colonoscopic surveillance program should be instituted for this high-risk population. In addition, the majority of patients were found to have right-sided tumors—as such, it is imperative that a complete colonoscopic screening evaluation rather than a limited sigmoidoscopic evaluation be conducted, regardless of patient age. The limitations of our study include the retrospective design and a potentially underpowered analysis given the small sample size. However, given that our study is singleinstitution data, we are able to describe more thoroughly the operative management and outcomes of our patients and the standardized approach in which they are generally cared for.
Conclusions Based on review of our transplant population, colorectal cancer arising de novo after solid organ transplantation does not seem to be elevated over the non-transplant population. Operative morbidity is high, but generally minor, and survival appears congruent with previously reported data regarding the general population. Vigilance and
603
appropriate screening by full colonoscopic evaluation must be maintained in this patient population, as some will not be symptomatic upon presentation.
Conflict of Interest The authors have no disclosures.
References 1. Penn I, Hammond W, Brettschneider L, Starzl TE. Malignant lymphomas in transplantation patients. Transplantation proceedings. 1969 Mar;1(1):106–12. 2. Oo YH, Gunson BK, Lancashire RJ, Cheng KK, Neuberger JM. Incidence of cancers following orthotopic liver transplantation in a single center: comparison with national cancer incidence rates for England and Wales. Transplantation. 2005 Sep 27;80(6):759–64. 3. Haagsma EB, Hagens VE, Schaapveld M, van den Berg AP, de Vries EG, Klompmaker IJ, et al. Increased cancer risk after liver transplantation: a population-based study. Journal of hepatology. 2001 Jan;34(1):84–91. 4. Penn I. Posttransplantation de novo tumors in liver allograft recipients. Liver transplantation and surgery : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 1996 Jan;2(1):52–9. 5. Rudraraju M, Osowo AT, Singh V, Carey EJ. Do patients need more frequent colonoscopic surveillance after liver transplantation? Transplantation proceedings. 2008 Jun;40(5):1522–4. 6. Silva MA, Jambulingam PS, Mirza DF. Colorectal cancer after orthotopic liver transplantation. Critical reviews in oncology/ hematology. 2005 Oct;56(1):147–53. 7. Johnson EE, Leverson GE, Pirsch JD, Heise CP. A 30-year analysis of colorectal adenocarcinoma in transplant recipients and proposal for altered screening. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 2007 Mar;11(3):272–9. 8. Atassi T, Thuluvath PJ. Risk of colorectal adenoma in liver transplant recipients compared to immunocompetent control population undergoing routine screening colonoscopy. Journal of clinical gastroenterology. 2003 Jul;37(1):72–3. 9. Selgrad M, Koornstra JJ, Fini L, Blom M, Huang R, Devol EB, et al. (2008 Oct) JC virus infection in colorectal neoplasia that develops after liver transplantation. Clin Cancer Res 14(20):6717–21. [Comparative Study Research Support, N.I.H., Extramural]. 10. Waldner M, Schimanski CC, Neurath MF. Colon cancer and the immune system: the role of tumor invading T cells. World J Gastroenterol. [Editorial Review]. 2006 Dec 7;12(45):7233–8. 11. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Annals of surgery. 2004 Aug;240(2):205–13. 12. Adami J, Gabel H, Lindelof B, Ekstrom K, Rydh B, Glimelius B, et al. Cancer risk following organ transplantation: a nationwide cohort study in Sweden. British journal of cancer. 2003 Oct 6;89(7):1221–7. 13. Kyllonen L, Salmela K, Pukkala E. Cancer incidence in a kidneytransplanted population. Transplant international : official journal of the European Society for Organ Transplantation. 2000;13 Suppl 1: S394-8. 14. Brunner FP, Landais P, Selwood NH. Malignancies after renal transplantation: the EDTA-ERA registry experience. European Dialysis and Transplantation Association-European Renal Association. Nephrology, dialysis, transplantation : official publication of the
604 European Dialysis and Transplant Association - European Renal Association. 1995;10 Suppl 1:74–80. 15. Stewart T, Henderson R, Grayson H, Opelz G. Reduced incidence of rectal cancer, compared to gastric and colonic cancer, in a population of 73,076 men and women chronically immunosuppressed. Clinical cancer research : an official journal of the American Association for Cancer Research. 1997 Jan;3(1):51–5. 16. Buell JF, Papaconstantinou HT, Skalow B, Hanaway MJ, Alloway RR, Woodle ES. De novo colorectal cancer: five-year survival is markedly lower in transplant recipients compared with the general population. Transplantation proceedings. 2005 Mar;37(2):960–1.
J Gastrointest Surg (2014) 18:599–604 17. Papaconstantinou HT, Sklow B, Hanaway MJ, Gross TG, Beebe TM, Trofe J, et al. Characteristics and survival patterns of solid organ transplant patients developing de novo colon and rectal cancer. Diseases of the colon and rectum. 2004 Nov;47(11):1898–903. 18. Winawer SJ, Fletcher RH, Miller L, Godlee F, Stolar MH, Mulrow CD, et al. Colorectal cancer screening: Clinical guidelines and rationale. Gastroenterology. 1997;(112):594–642. 19. Winawer SJ, Fletcher RH, Rex D, Bond J, Burt R, Ferrucci J, et al. Colorectal cancer screening and surveillance: Clinical guidelines and rational - Update based on new evidence. Gastroenterology. 2003;(124):544–560.
