Colon and Rectal Complications after Heart and Lung Transplantation

Colon and Rectal Complications after Heart and Lung Transplantation Hilary J Goldberg, MD, Marshall I Hertz, MD, Rocco Ricciardi, MD, Robert D Madoff, MD, FACS, Nancy N Baxter, MD, PhD, Kelli M Bullard, MD, FACS Gastrointestinal complications of solid organ transplantation have been well described, but little attention has been paid to colorectal disorders in particular. The purpose of this study was to identify the incidence and severity of colorectal complications among a large cohort of heart and lung transplant recipients. STUDY DESIGN: We reviewed the medical records of heart, lung, and heart-lung transplant recipients at a single institution between 1978 and 2004. Complications were identified based on need for consultation, endoscopy, or operation by a colorectal surgeon after transplantation. RESULTS: Of 1,012 patients who received transplantations (530 heart, 435 lung, 47 heart-lung), 56 patients (6%) required evaluation for 84 colorectal problems. Incidence of complications was 7% in lung transplant recipients, 6% in heart-lung transplant recipients, and 4% in heart transplant recipients. Forty-four events (52%) were considered major (diverticulitis, perforation, malignancy, and other) and 40 (48%) were minor (polyps, pseudo-obstruction treated medically or endoscopically, benign anorectal disease, and other). Twenty-three (27%) required colectomy and 9 (10%) necessitated anal operation. Thirty-six (43%) required less-invasive interventions (endoscopy, minor anorectal procedures, and other). Eighteen (21%) were treated with medical therapy alone. Six patients died from colorectal disease (7%). CONCLUSIONS: Colorectal complications are a considerable source of morbidity and mortality after heart and lung transplantation. These complications occur more frequently in patients who undergo lung and heart-lung transplantation as compared with heart transplantation alone. (J Am Coll Surg 2006;202:55–61. © 2006 by the American College of Surgeons) BACKGROUND:

The alimentary tract is a source of nonallograft complications after solid organ transplantation and the gastrointestinal (GI) problems experienced by thoracic solid-organ transplant recipients mirror those of renal transplant patients.1 The most common GI abnormalities described after heart and heart-lung transplantation, excluding diarrhea, include perforated viscus, cholecystitis, esophagitis, peptic ulcer disease, and cytomegalovirus infection of the GI tract.2-5 Colorectal (CR) and anorectal (AR) problems account for a small subset of the total GI complications reported. In studies involving fewer than 150 patients,

perforated diverticulitis has been described as the most common complication involving the lower GI tract after thoracic transplantation.2,5 Other reported CR and AR complications include colonic perforation, cecal volvulus, toxic megacolon, and perianal abscess.2-5 Studies in thoracic solid organ recipients have been limited by small sample size, with cohort size typically less than 200 patients. Existing studies have rarely focused specifically on colon and rectal diseases. In addition, few studies have included data on lung transplant recipients. The purpose of this study was to identify the incidence and severity of CR complications in a cohort of over 1,000 heart, lung, and heart-lung transplantation patients.

Competing Interests Declared: None. Received June 27, 2005; Revised August 24, 2005; Accepted August 29, 2005. From the Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, University of Minnesota (Goldberg, Hertz); Department of Surgery, University of Minnesota (Ricciardi, Madoff, Baxter, Bullard); and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN (Bullard). Correspondence address: Kelli M Bullard, MD, FACS, MMC 450, 420 Delaware St SE, Minneapolis, MN 55455.

© 2006 by the American College of Surgeons Published by Elsevier Inc.

METHODS Patient selection

We retrospectively reviewed the medical records of all heart, lung, and heart-lung transplant recipients who required evaluation by a member of the Division of Co-

55

ISSN 1072-7515/06/$32.00 doi:10.1016/j.jamcollsurg.2005.08.025

56

Goldberg et al

Complications after Heart and Lung Transplantation

Abbreviations and Acronyms

AR CR CSA GI

⫽ ⫽ ⫽ ⫽

anorectal colorectal cyclosporine gastrointestinal

lon and Rectal Surgery at the University of Minnesota between January 1, 1978, and November 15, 2004. Patients were included in the study if they required an opinion or intervention (endoscopic or surgical) by a CR surgeon on or after the date of transplantation. Events were classified as primarily CR or AR. Major complications were defined as diverticulitis, colonic perforation, malignancy, or other disorders requiring surgical intervention or major medical intervention. Minor complications were defined as benign AR disease requiring medical therapy or same-day operation, or minor colonic disease not requiring operation or major medical therapy (colonic polyps, pseudo-obstruction treated medically or endoscopically, and other). Patients were excluded from the study if the intervention(s) occurred before transplantation, were performed for the purpose of screening, or resulted in a normal evaluation despite suspected CR or AR disease. The study protocol was approved by the University of Minnesota institutional review board. Immunosuppression

The immunosuppressive regimen used in the management of lung and heart-lung transplant recipients consisted of a single oral dose of either cyclosporine (CSA) (5 mg/kg) or tacrolimus (0.05 mg/kg) before transplantation. Methylprednisone 500 mg was given IV after release of the pulmonary artery clamp, followed by 250 mg IV every 8 hours for three doses. Prednisone was then started at 0.5 mg/kg/d in two divided doses tapering to 0.1 mg/kg/d at 6 months posttransplantation. Patients received either CSA (target level 150 to 250 ng/mL measured by high-performance liquid chromatography in whole blood) or tacrolimus (target level 12 to 15 ng/mL measured by microparticle enzyme immunoassay in whole blood) depending on physician preference. Between May 1986 and October 1996, immunosuppression included azathioprine 2 to 2.5 mg/kg/d. After October 1996, patients received mycophenolate mofetil 2 to 3 g/d. Heart transplant recipients received a single oral dose

J Am Coll Surg

of either CSA (2 mg/kg) or tacrolimus (0.05 mg/kg) pretransplantation. Methylprednisolone 10 mg/kg was given IV intraoperatively followed by 125 mg IV every 8 hours for three doses. Mycophenolate 1,000 mg orally or rapamycin 6 mg orally was given preoperatively as part of induction therapy. Prednisone was then started at 1 mg/kg in two divided doses tapering off by month 5 in patients who remained rejection free at month 3. Patients received either CSA (target level 100 to 175 ng/mL by 12 months posttransplantation) or tacrolimus (target level 8 to 10 ng/mL by 12 months posttransplantation) depending on physician preference and study participation. Similarly, mycophenolate 2 to 3 g/d in divided doses (target level 2 to 4 ng/mL), azathioprine 1 mg/kg/d, or rapamycin 2 to 5 mg/d (target level 6 to 10 ng/mL) were administered based on physician preference and study participation. Evaluation and followup

Pretransplantation colon cancer screening for lung transplant recipients included three stool guaiac assessments and routine screening as prescribed by the patients’ primary care providers, or evaluation as dictated by pertinent signs and symptoms. In accordance with current protocols, prospective heart transplant recipients older than age 50 years who were deemed medically fit for interventions also underwent screening colonoscopy before transplantation. After transplantation, patients were seen once to twice weekly in the transplantation clinic until their conditions stabilized. Intervals between visits were gradually increased to reach an eventual followup schedule of quarterly to annually, based on active medical issues and new symptoms or problems. Patients evaluated in the clinic setting and as hospital inpatients were included in this study. Patients were referred to the Division of Colon and Rectal Surgery at the discretion of their transplantation or primary physicians. RESULTS Between January 1, 1978 and November 15, 2004, 1,012 patients received thoracic transplantations (530 heart, 435 lung, and 47 heart-lung recipients). The ratio of men to women was approximately 2:1. Mean age at transplantation was 52.6 years (range 20 to 71 years). The most common disorder necessitating lung transplantation was obstructive lung disease. Heart transplantation was performed most often for ischemic car-

Vol. 202, No. 1, January 2006

Goldberg et al

Table 1. Demographic Data Characteristic

Gender Male Female Total Organ transplanted Heart Lung Heart-lung Age at transplant (y) Mean Range Disease COPD/␣1 AT deficiency Idiopathic pulmonary fibrosis Pulmonary hypertension CF/bronchiectasis Other lung disease Ischemic CMP Idiopathic CMP Congenital cyanotic heart disease Other cardiac disease

Complications after Heart and Lung Transplantation

57

Table 2. Comorbid Colorectal Conditions Before Transplantation n

38 18 56 20 32 4 52.6 20–71 22 3 2 4 3 13 6 2 1

␣1 AT deficiency, ␣1 antitrypsin deficiency; CF, cystic fibrosis; CMP, cardiomyopathy.

diomyopathy. Heart-lung transplantations were performed for primary pulmonary hypertension, ␣-1 antitrypsin deficiency, Eisenmenger’s syndrome, and congenital cyanotic heart disease (Table 1). Pretransplantation comorbidities were infrequent, and only eight patients had preexisting CR or AR disease (Table 2). After transplantation, 56 patients (incidence, 6%) required evaluation for 84 CR and AR problems (Table 3). The incidence of CR and AR disease was 7% in lung transplant recipients, 6% in heart-lung transplant recipients, and 4% in heart transplant recipients. Twenty-two patients had more than one problem. Mean age at first CR and AR complication was 59.6 years (range 23 to 80 years). Mean time to first complication was 4.3 years (range 0 to 15.3 years) after transplantation. Mean followup time for the cohort was 6.4 years (range 2 months to 17.3 years). Thirty-six of the 56 patients were alive at the conclusion of the study period. Major complications

Major complications (diverticulitis, colonic perforation, malignancy, or other) occurred 44 times (Table 3). Of the major complications, diverticulitis was experienced most often (14 patients; incidence, 1.4%). Three cases

Disease

n

Colon/rectal polyps Diverticular disease Hemorrhoidal disease Malignancy Systemic disease Total

3 4 1 1 1 10

were associated with colonic perforation and one with stricture. Two cases occurred in patients with pretransplantation histories of diverticular disease, and one patient suffered recurrent diverticulitis after transplantation. The vast majority (11 of 14 patients) required colectomy. Diverticular disease resolved in all patients after institution of definitive therapy (operation or bowel rest plus broad spectrum antibiotics). Malignancy was the second most common major complication (n ⫽ 10; incidence 1%). Adenocarcinoma of the colon was most frequently seen (n ⫽ 5; incidence 0.5%). The mean age of these patients at the time of transplantation was 55 years (range 39 to 71 years). The mean age at the time of cancer diagnosis was 62 years (range 47 to 72 years). Average time from transplantation to cancer diagnosis was 92 months (range 3 to 152 months). Four of the five patients with adenocarcinoma had metastatic disease at the time of diagnosis. Three were managed surgically, one medically, and one with combined therapy. The patient mortality rate from adenocarcinoma of the colon was 60%. Although pretransplantation screening colonoscopy was routinely recomTable 3. Colorectal and Anorectal Complications after Transplantation Organ transplanted

n No. of complications Colorectal Total Diverticulitis Polyps Pseudo-obstruction CA/PTLD Anorectal Total SCCA anus Hemorrhoids Other

Heart

Lung

Heart-lung

20 31

32 49

4 4

16 5 6 1 4

23 9 8 3 3

2 0 2 0 0

6 1 5 9

12 2 10 14

1 1 0 1

CA, carcinoma; PTLD, posttransplantation lymphoproliferative disease; SCCA, squamous cell carcinoma.

58

Goldberg et al

Complications after Heart and Lung Transplantation

mended for patients who would tolerate the procedure, specific screening information for individual patients was unavailable. Squamous cell carcinoma of the anus developed in four patients (incidence 0.4%). These patients were younger than the adenocarcinoma patients, with a mean age of 43 years at the time of transplantation (range 34 to 58 years), and a mean age of 48 years at the time of cancer diagnosis (range 43 to 58 years). Average time from transplantation to cancer diagnosis was 66 months (range 8 to 108 months). Two patients received combined surgical and medical therapy and two were treated with medical therapy alone (chemotherapy plus radiation). All four patients remain alive 4 months to 7 years after squamous cell carcinoma diagnosis. Posttransplantation lymphoproliferative disease developed in two patients, one of the colon and one of the rectum (incidence 0.2%). Their ages at transplantation were 57 and 59 years, and ages at diagnosis were 58 and 62 years, respectively. Both patients were managed with antitumor agents. One remains in remission 1 year after posttransplantation lymphoproliferative disease diagnosis, and the second, whose posttransplantation lymphoproliferative disease was discovered 1 month before the conclusion of this study, remains on therapy. Colonic pseudo-obstruction (n ⫽ 4; incidence 0.4%) was most often, but not exclusively, observed in the early posttransplantation period. Two of the four cases occurred on postoperative day 1, and one on postoperative day 10. One patient presented with pseudo-obstruction 5 months after undergoing transplantation. The majority of patients with pseudo-obstruction had evidence of perforation and required surgical intervention (3 of 4, 75%). In addition, spontaneous colonic perforation occurred once. Other major complications included cytomegalovirus colitis, ischemic colitis, necrotizing fasciitis, rectal prolapse, pneumatosis intestinalis, urethra-rectal fistula, and incarcerated diaphragmatic hernia. Minor complications

Minor problems (colonic polyps, pseudo-obstruction treated medically or endoscopically, benign AR disease, and other) occurred frequently in our patients (40 events in 56 patients, Table 3). CR polyps were most common; all were treated endoscopically. Symptoms or complications of hemorrhoids were experienced by 15 patients. One patient suffered a colonic pseudo-obstruction that resolved

J Am Coll Surg

Table 4. Outcomes of Colorectal and Anorectal Complications Outcomes

n

Resolution Persistent Surgical complication Death Unknown Total

62 9 6 6 1 84

without surgical intervention. Other minor complications included pruritis ani, enterocele, cellulitis, fecal incontinence, and lipoma. Treatment and outcomes

Colectomy was required in 23 of 41 CR complications. Surgical intervention was undertaken for seven anal problems, excluding malignancy. Overall, of 84 CR and AR complications, 32 needed surgical intervention. Medical therapy alone was adequate management for 18 CR and AR problems. The majority of CR and AR complications resolved after treatment (Table 4). Nine of the disorders were persistent despite intervention. Six deaths occurred (7% mortality). Three heart transplant recipients died of adenocarcinoma of the colon. Another died of sepsis after colectomy for a bleeding cecal ulcer. Two lung transplant recipients died, one with a nocardial buttock abscess and disseminated nocardia. Another suffered a splenic flexure perforation complicated by peritonitis and abdominal compartment syndrome, and died as a result of this event. DISCUSSION Although CR and AR problems are common complications of abdominal solid organ transplantation, little is known about their incidence and severity in thoracic transplantation. Small studies focusing on complications of the lower GI tract have been performed in renal transplant recipients, and the incidence of colonic complications in these reports ranges from 7.4% to 8.6%.6,7 A larger series following more than 2,000 renal transplant patients over 30 years found a 0.5% incidence of colonic problems.8 In the thoracic transplantation population, studies are limited. One report examining 210 lung transplant recipients demonstrated a 13% incidence of colonic problems.9 Data investigating the incidence of specific colonic complications such as diverticulitis or perforation in thoracic transplantation described lower cumulative incidences of disease of 0.7% to 8.6%.10-13 In

Vol. 202, No. 1, January 2006

Goldberg et al

our study, we reviewed a large series of over 1,000 thoracic transplant recipients and identified a 6% incidence of CR or AR disease. To our knowledge, our series is the largest to report lower GI complications in this patient population. Diverticulitis was the most frequent CR problem encountered in our cohort. Other investigators have reported a similar incidence of this disease. For example, Maurer9 described a 4% incidence of diverticulitis in lung transplant patients. The incidence of diverticulitis in the general population has been variably reported, but diverticulitis appears to be responsible for approximately 25 to 50 hospital admissions per 100,000 population (0.025% to 0.053% incidence).14,15 Our data suggest that this disease can be at least 20-fold more common in the thoracic transplantation population (incidence 1.4%). This finding is consistent with those of Qasabian and colleagues16 who described an incidence rate ratio for diverticulitis posttransplantation of 22 compared with the general population. Although fewer than onethird of diverticulitis patients in the general population require colectomy,14,15 the majority of patients in both our series and others underwent surgical management.2,5,17 Similarly, Lederman and colleagues18 encountered a 1.1% incidence of complicated diverticulitis in a cohort of renal transplant recipients, and all cases led to colectomy. These data suggest that the clinical course of diverticulitis might be more fulminant in transplantation patients. Additional investigation of use of aggressive colonic screening pre- and posttransplantation and the role of early or even prophylactic surgical intervention is warranted. The incidence of lower GI malignancies in thoracic transplant patients is less well documented than that of diverticulitis. An early report on malignant neoplasms after cardiac transplantation described a single case of adenocarcinoma of the colon in 124 patients evaluated.19 In a large study of 73,076 subjects requiring chronic immunosuppression after heart or kidney transplantation and followed for up to 10 years after transplantation, 75 cases of colon cancer and 15 cases of rectal cancer were observed.20 Our reported incidence of 0.5% is consistent with the incidence of 0.1% observed in that series,20 and is striking in light of the approximately 6% lifetime risk of colon cancer seen in the general population.21 Mortality data are not provided in that study, but our 60% mortality rate in patients with adenocarcinoma is concerning, and might suggest that cancer in these

Complications after Heart and Lung Transplantation

59

patients has a more aggressive natural history than in the general population, or that patients with this disease reach diagnosis in later stages of illness. In light of this observation, we believe that routine pretransplantation screening, ideally with colonoscopy, should be performed in patients who are medically fit. In patients in whom medical comorbidities prohibit the procedure, early posttransplantation colonoscopy should be performed. Thereafter, screening according to high-risk guidelines (colonoscopy every 5 years) can be beneficial. It is important to note that screening for CR carcinoma has not been prospectively studied in this population and optimal timing and frequency has yet to be determined. Data on the frequency of other types of lower GI cancers is lacking in lung and heart transplantation patients, but our experience with squamous cell carcinoma of the anus is consistent with that of abdominal solid organ transplant recipients. Ogunbiyi and colleagues22 found a 0.7% incidence of squamous cell carcinoma of the anus in a small cohort of renal transplant recipients. The authors of this and other studies have shown a substantially increased incidence of such malignancies, and of anogenital intraepithelial neoplasia and human papillomavirus infection, in renal transplant recipients compared with dialysis patients and immunocompetent individuals.22-24 Despite the high survival rate after squamous cell carcinoma observed in our cohort, such malignancies have been associated with a more aggressive natural history in immunosuppressed patients than in the general population.25 Various screening methods, including cytologic and pathologic examination and virologic testing, have been discussed in the renal transplantation literature,25,26 and should be considered in thoracic transplant recipients as well. The incidence of pseudo-obstruction in our study is lower than the 1.3% to 3.5% reported in heart transplant recipients in other series.4,17,27 In an analysis of 71 lung transplant recipients by Smith and colleagues,28 adynamic ileus was described in 4 patients (incidence, 6%), all in the early (⬍ 30 days) posttransplantation period. The rate of perforation in these patients with megacolon was not reported. Another study reported a 1.9% incidence of megacolon occurring within 2 weeks of transplantation.9 In addition, our experience with colonic dilation is ⬍ 1.2% incidence described in renal transplant recipients.29 The predominantly early occurrence of pseudo-obstruction is likely related to narcotic use after operation, immobility, and hemodynamic in-

60

Goldberg et al

Complications after Heart and Lung Transplantation

stability. We suspect that heightened awareness of the side effects of narcotic administration and recent improvements in critical care practices, and the decreased risk of obstruction after thoracic as opposed to abdominal operation, might be responsible for the relatively low incidence of this problem in our patients. Corticosteroid use after transplantation also has been implicated in the development of colonic perforation.30 In one study, such cases were all associated with an identifiable underlying pathologic abnormality.30 Survival rates in that series were low. Similarly, colon perforation related to underlying diverticulitis has been reported after lung transplantation.12 Spontaneous colonic perforation has also been described in thoracic transplant recipients, with an incidence of 0.47% to 5.6%.9,28,31 The majority of cases occur late after transplantation, as in our patient, but unlike our patient, often involve the right colon. Our study also identified a high rate of minor complications that, although not life-threatening, necessitated interventions in the posttransplantation period. The incidence of AR disease after thoracic transplantation is not well documented. One report described 2 cases of AR disease identified from 92 transplant recipients.32 Another reported internal hemorrhoids in 39% of heart transplant patients.33 Twenty-three percent of complications identified in our series were minor AR problems. Colonic polyps also occurred frequently in our patients. Another study undertaken to look specifically at the incidence of CR polyps in cardiac transplant patients 1 year or more after transplantation found an incidence of polyps of 32%.33 We found considerably fewer instances of polyps (1.6% incidence) in our study, likely because we did not perform serial screening procedures on all patients after transplantation. Potential problems with our study include its retrospective design and the lack of a comparison group with which to evaluate the incidence of disease. The correlation of our experience with those of other investigators in both thoracic and intraabdominal solid organ transplantation supports the findings in this study. In addition, only patients referred to a CR surgeon were included in this study. Patients treated by general surgeons and those managed at outside facilities were not evaluated, and the total incidence of CR disease might be underreported. On the other hand, our data might overestimate the incidence of major problems because general surgeons and other practitioners can manage minor difficulties without referral. Finally, we were unable to

J Am Coll Surg

retrospectively assess the timing of rejection episodes and steroid bursts in relation to the development of complications. An association between rejection treated with steroids and GI complications has been observed in other studies, and our cohort of heart transplant recipients, in whom aggressive attempts to wean steroids were made, experienced almost half of the incidence of CR and AR complications as the rest of our group. Without determining the temporal relationship between rejection episodes and CR and AR problems in our patients, no assessment of association can be made in our study. Despite these limitations, we believe that this large series of patients sheds light on the incidence and severity of CR disease in the thoracic transplantation population. CR and AR disease was not infrequent after thoracic transplantation, and the majority of patients required some type of surgical intervention. Morbidity and mortality were considerable. For example, threequarters of patients with diverticulitis required colectomy and two-thirds of patients with colonic adenocarcinoma died. Perforation was also highly lethal in our report and others. We believe that aggressive monitoring of transplant recipients with interventions such as routine colonoscopic screening for malignancy before transplantation and routine postoperative cytologic screening for human papilloma virus and anal intraepithelial neoplasia after transplantation, proactive measures to avoid colonic pseudo-obstruction, particularly early after transplantation, and early intervention for symptomatic diverticulitis, warrant additional investigation. These interventions might reduce the incidence of these problems and limit their morbidity. CR and AR disorders are not uncommon after thoracic solid organ transplantation, and a wide variety of disorders occur. These problems can be associated with substantial morbidity and mortality. A heightened awareness of these conditions can prevent hospitalization, operation, or death in this population. Author Contributions

Study conception and design: Goldberg, Hertz, Baxter, Bullard Acquisition of data: Goldberg, Hertz, Ricciardi, Madoff, Baxter, Bullard Analysis and interpretation of data: Goldberg, Bullard Drafting of manuscript: Goldberg, Ricciardi, Madoff, Bullard Critical revision: Hertz, Madoff, Baxter, Bullard

Vol. 202, No. 1, January 2006

Goldberg et al

Statistical expertise: Baxter Obtaining funding: Hertz Supervision: Bullard

17. 18.

REFERENCES 1. Karakayali H, Moray G, Caliskan K, et al. Gastrointestinal complications requiring surgical management in renal transplant recipients. Transplant Proc 2002;34:2122–2123. 2. Steed DL, Brown B, Reilly JJ, et al. General surgical complications in heart and heart-lung transplantation. Surgery 1985;98: 739–744. 3. Merrell SW, Ames SA, Nelson EW, et al. Major abdominal complications following cardiac transplantation. Arch Surg 1989; 124:889–894. 4. Kirklin JK, Holm MD, Aldrete JS, et al. Gastrointestinal complications after cardiac transplantation. Ann Surg 1990;211: 538–542. 5. Augustine SM, Yeo CJ, Buchman TG, et al. Gastrointestinal complications in heart and heart-lung transplant patients. J Heart Lung Transplant 1991;10:547–556. 6. Archibald SD, Jirsch DW, Bear RA. Gastrointestinal complications of renal transplantation. 2. The colon. Can Med Assoc J 1978;119:1301–1305. 7. Lao A, Bach D. Colonic complications in renal transplant recipients. Dis Colon Rectum 1988;31:130–133. 8. Soravia C, Baldi A, Kartheuser A, et al. Acute colonic complications after kidney transplantation. Acta Chir Belg 1995;95:157–161. 9. Maurer JR. The spectrum of colonic complications in a lung transplant population. Ann Transplant 2000;5:54–57. 10. Khan S, Eppstein AC, Anderson GK, et al. Acute diverticulitis in heart- and lung transplant patients. Transplant Int 2001;14: 12–15. 11. Detry O, Defraigne JO, Meurisse M, et al. Acute diverticulitis in heart transplant recipients. Transplant Int 1996;9:376–379. 12. Beaver TM, Fullerton DA, Zamora MR, et al. Colon perforation after lung transplantation. Ann Thoracic Surg 1996;62: 839–843. 13. Fenton JJ, Cicale MJ. Sigmoid diverticular perforation complicating lung transplantation. J Heart Lung Transplant 1997;16: 681–685. 14. Salem L, Anaya DA, Flum D. Temporal changes in the management of diverticulitis. J Surg Res 2005;124:318–323. 15. Kang JY, Hoare J, Tinto A, et al. Diverticular disease of the colon—on the rise: a study of hospital admissions in England between 1989/1990 and 1999/2000. In: Everhart JE, ed. Digestive disease in the United States: epidemiology and impact. Washington, DC: US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institutes of Diabetes and Digestive and Kidney Diseases; 1994:553–565. 16. Qasabian RA, Meagher AP, Lee R, et al. Severe diverticulitis after

19. 20.

21.

22. 23. 24. 25. 26.

27. 28. 29. 30. 31. 32. 33.

Complications after Heart and Lung Transplantation

61

heart, lung, and heart-lung transplantation. J Heart Lung Transplant 2004;23:845–849. Watson CJE, Jamieson NV, Johnston PS, et al. Early abdominal complications following heart and heart-lung transplantation. Br J Surg 1991;78:699–704. Lederman ED, Conti DJ, Lempert N, et al. Complicated diverticulitis following renal transplantation. Dis Colon Rectum 1998;41:613–618. Krikorian JG, Anderson JL, Bieber CP, et al. Malignant neoplasms following cardiac transplantation. JAMA 1978;240: 639–643. Stewart T, Henderson R, Grayson H, Opelz G. Reduced incidence of rectal cancer, compared to gastric and colon cancer, in a population of 73,076 men and women chronically immunosuppressed. Clin Cancer Res 1997;3:351–355. Gordon PH. Malignant neoplasms of the colon. In: Principles and practice of surgery for the colon, rectum, and anus. Gordon PH and Nivatuongs S eds. 2nd ed. St Louis, MO: Quality Medical Publishing, Inc.; 1999:575⫺717. Ogunbiyi OA, Scholefield JH, Raftery AT, et al. Prevalence of anal human papillomavirus infection and intraepithelial neoplasia in renal allograft recipients. Br J Surg 1994;81:365–367. Penn I. Cancers of the anogenital region in renal transplant recipients. Analysis of 65 cases. Cancer 1986;58:611–616. Fairley CK, Sheil AG, McNeil JJ, et al. The risk of ano-genital malignancies in dialysis and transplant patients. Clin Nephrol 1994;41:101–105. Sillman FH, Sentovich S, Shaffer D. Ano-genital neoplasia in renal transplant patients. Ann Transplant 1997;2:59–66. Lecatsas G, Dreyer L, Mieny CJ, Nel PJ. Successive urinary papillomavirus excretion, condylomata acuminata and urogenital epithelial malignant disease after renal transplantation. S Afr Med J 1985;67:374–376. Colon R, Frazier OH, Kahan BD, et al. Complications in cardiac transplant patients requiring general surgery. Surgery 1988; 103:32–38. Smith PC, Slaughter MS, Petty MG, et al. Abdominal complications after lung transplantation. J Heart Lung Transplant 1995;14:44–51. Koneru B, Selby R, O’Hair DP, et al. Nonobstructing colonic dilatation and colon perforations following renal transplantation. Arch Surg 1990;125:610–613. Sterioff S, Orringer MB, Cameron JL. Colon perforations associated with steroid therapy. Surgery 1974;75:56–58. De Simone P, Journe S, Feron P, Gelin M. Right colon perforation in a lung graft patient. Transplantation 2004;77:1919– 1920. Mueller XM, Tevearai HT, Stumpe F, et al. Gastrointestinal disease following heart transplantation. World J Surg 1999;23: 650–656. Rodriguez-Larrain JM, Ziebert JJ, Kfoury AG, et al. Incidence of adenomatous colorectal polyps in cardiac transplant recipients. Transplantation 1997;64:528–530.