Clin Colon Rectal Surg 2015; 28(02): 103-111
DOI: 10.1055/s-0035-1547337
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Radiation Proctopathy

Marc B. Grodsky
1   Section of Colon and Rectal Surgery, MedStar Washington Hospital Center, Washington, District of Columbia
,
Shafik M. Sidani
2   Department of Colorectal Surgery, Virginia Hospital Center Physician Group, Arlington, Virginia
› Author Affiliations
Further Information

Publication History

Publication Date:
25 May 2015 (online)

Abstract

Radiation therapy is a widely utilized treatment modality for pelvic malignancies, including prostate cancer, rectal cancer, and cervical cancer. Given its fixed position in the pelvis, the rectum is at a high risk for injury secondary to ionizing radiation. Despite advances made in radiation science, up to 75% of the patients will suffer from acute radiation proctitis and up to 20% may experience chronic symptoms. Symptoms can be variable and include diarrhea, bleeding, incontinence, and fistulization. A multitude of treatment options exist. This article summarizes the latest knowledge relating to radiation proctopathy focusing on the vast array of treatment options.

 
  • References

  • 1 Hauer-Jensen M, Wang J, Boerma M, Fu Q, Denham JW. Radiation damage to the gastrointestinal tract: mechanisms, diagnosis, and management. Curr Opin Support Palliat Care 2007; 1 (1) 23-29
  • 2 Sher DJ. Cost-effectiveness studies in radiation therapy. Expert Rev Pharmacoecon Outcomes Res 2010; 10 (5) 567-582
  • 3 Bacon CG, Giovannucci E, Testa M, Glass TA, Kawachi I. The association of treatment-related symptoms with quality-of-life outcomes for localized prostate carcinoma patients. Cancer 2002; 94 (3) 862-871
  • 4 Bacon CG, Giovannucci E, Testa M, Kawachi I. The impact of cancer treatment on quality of life outcomes for patients with localized prostate cancer. J Urol 2001; 166 (5) 1804-1810
  • 5 Hong JJ, Park W, Ehrenpreis ED. Review article: current therapeutic options for radiation proctopathy. Aliment Pharmacol Ther 2001; 15 (9) 1253-1262
  • 6 Swaroop VSGC, Gostout CJ. Endoscopic treatment of chronic radiation proctopathy. J Clin Gastroenterol 1998; 27 (1) 36-40
  • 7 Hayne D, Vaizey CJ, Boulos PB. Anorectal injury following pelvic radiotherapy. Br J Surg 2001; 88 (8) 1037-1048
  • 8 Novak JM, Collins JT, Donowitz M, Farman J, Sheahan DG, Spiro HM. Effects of radiation on the human gastrointestinal tract. J Clin Gastroenterol 1979; 1 (1) 9-39
  • 9 Meyer J, Czito B, Yin FF, Willett C. Advanced radiation therapy technologies in the treatment of rectal and anal cancer: intensity-modulated photon therapy and proton therapy. Clin Colorectal Cancer 2007; 6 (5) 348-356
  • 10 Meyer JJ, Willett CG, Czito BG. Emerging role of intensity-modulated radiation therapy in anorectal cancer. Expert Rev Anticancer Ther 2008; 8 (4) 585-593
  • 11 Willett CG ; Willet Cg. Technical advances in the treatment of patients with rectal cancer. Int J Radiat Oncol Biol Phys 1999; 45 (5) 1107-1108
  • 12 Melian E, Mageras GS, Fuks Z , et al. Variation in prostate position quantitation and implications for three-dimensional conformal treatment planning. Int J Radiat Oncol Biol Phys 1997; 38 (1) 73-81
  • 13 Ling CC, Burman C, Chui CS , et al. Conformal radiation treatment of prostate cancer using inversely-planned intensity-modulated photon beams produced with dynamic multileaf collimation. Int J Radiat Oncol Biol Phys 1996; 35 (4) 721-730
  • 14 Fraass BA, Kessler ML, McShan DL , et al. Optimization and clinical use of multisegment intensity-modulated radiation therapy for high-dose conformal therapy. Semin Radiat Oncol 1999; 9 (1) 60-77
  • 15 Drzymala RE, Mohan R, Brewster L , et al. Dose-volume histograms. Int J Radiat Oncol Biol Phys 1991; 21 (1) 71-78
  • 16 Dearnaley DP, Khoo VS, Norman AR , et al. Comparison of radiation side-effects of conformal and conventional radiotherapy in prostate cancer: a randomised trial. Lancet 1999; 353 (9149) 267-272
  • 17 Bayley AJ, Catton CN, Haycocks T , et al. A randomized trial of supine vs. prone positioning in patients undergoing escalated dose conformal radiotherapy for prostate cancer. Radiother Oncol 2004; 70 (1) 37-44
  • 18 van Lin EN, Hoffmann AL, van Kollenburg P, Leer JW, Visser AG. Rectal wall sparing effect of three different endorectal balloons in 3D conformal and IMRT prostate radiotherapy. Int J Radiat Oncol Biol Phys 2005; 63 (2) 565-576
  • 19 Noyes WR, Hosford CC, Schultz SE. Human collagen injections to reduce rectal dose during radiotherapy. Int J Radiat Oncol Biol Phys 2012; 82 (5) 1918-1922
  • 20 Michalski JM, Gay H, Jackson A, Tucker SL, Deasy JO. Radiation dose-volume effects in radiation-induced rectal injury. Int J Radiat Oncol Biol Phys 2010; 76 (3, Suppl): S123-S129
  • 21 Morgan SC, Waldron TS, Eapen L, Mayhew LA, Winquist E, Lukka H ; Genitourinary Cancer Disease Site Group of the Cancer Care Ontario Program in Evidence-based Care. Adjuvant radiotherapy following radical prostatectomy for pathologic T3 or margin-positive prostate cancer: a systematic review and meta-analysis. Radiother Oncol 2008; 88 (1) 1-9
  • 22 Gérard JP, Conroy T, Bonnetain F , et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol 2006; 24 (28) 4620-4625
  • 23 Rakovitch E, Fyles AW, Pintilie M, Leung PM. Role of mitomycin C in the development of late bowel toxicity following chemoradiation for locally advanced carcinoma of the cervix. Int J Radiat Oncol Biol Phys 1997; 38 (5) 979-987
  • 24 Bosset JF, Collette L, Calais G , et al; EORTC Radiotherapy Group Trial 22921. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 2006; 355 (11) 1114-1123
  • 25 Yeoh E, Horowitz M, Russo A , et al. Effect of pelvic irradiation on gastrointestinal function: a prospective longitudinal study. Am J Med 1993; 95 (4) 397-406
  • 26 Herold DM, Hanlon AL, Hanks GE. Diabetes mellitus: a predictor for late radiation morbidity. Int J Radiat Oncol Biol Phys 1999; 43 (3) 475-479
  • 27 Yang TJ, Oh JH, Son CH , et al. Predictors of acute gastrointestinal toxicity during pelvic chemoradiotherapy in patients with rectal cancer. Gastrointest Cancer Res 2013; 6 (5-6) 129-136
  • 28 Theodorescu D, Gillenwater JY, Koutrouvelis PG. Prostatourethral-rectal fistula after prostate brachytherapy. Cancer 2000; 89 (10) 2085-2091
  • 29 Shakespeare D, Mitchell DM, Carey BM , et al. Recto-urethral fistula following brachytherapy for localized prostate cancer. Colorectal Dis 2007; 9 (4) 328-331
  • 30 Shah SA, Cima RR, Benoit E, Breen EL, Bleday R. Rectal complications after prostate brachytherapy. Dis Colon Rectum 2004; 47 (9) 1487-1492
  • 31 Liauw SL, Sylvester JE, Morris CG, Blasko JC, Grimm PD. Second malignancies after prostate brachytherapy: incidence of bladder and colorectal cancers in patients with 15 years of potential follow-up. Int J Radiat Oncol Biol Phys 2006; 66 (3) 669-673
  • 32 Moon K, Stukenborg GJ, Keim J, Theodorescu D. Cancer incidence after localized therapy for prostate cancer. Cancer 2006; 107 (5) 991-998
  • 33 Okunieff P, Cornelison T, Mester M , et al. Mechanism and modification of gastrointestinal soft tissue response to radiation: role of growth factors. Int J Radiat Oncol Biol Phys 2005; 62 (1) 273-278
  • 34 Quastler H. Cell renewal and acute radiation damage. Radiology 1959; 73 (73) 161-165
  • 35 Rieder F, Brenmoehl J, Leeb S, Schölmerich J, Rogler G. Wound healing and fibrosis in intestinal disease. Gut 2007; 56 (1) 130-139
  • 36 Shadad AK, Sullivan FJ, Martin JD, Egan LJ. Gastrointestinal radiation injury: symptoms, risk factors and mechanisms. World J Gastroenterol 2013; 19 (2) 185-198
  • 37 François S, Bensidhoum M, Mouiseddine M , et al. Local irradiation not only induces homing of human mesenchymal stem cells at exposed sites but promotes their widespread engraftment to multiple organs: a study of their quantitative distribution after irradiation damage. Stem Cells 2006; 24 (4) 1020-1029
  • 38 François S, Mouiseddine M, Mathieu N , et al. Human mesenchymal stem cells favour healing of the cutaneous radiation syndrome in a xenogenic transplant model. Ann Hematol 2007; 86 (1) 1-8
  • 39 Bentzen SM. Preventing or reducing late side effects of radiation therapy: radiobiology meets molecular pathology. Nat Rev Cancer 2006; 6 (9) 702-713
  • 40 Paris F, Fuks Z, Kang A , et al. Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice. Science 2001; 293 (5528) 293-297
  • 41 Hasleton PS, Carr N, Schofield PF. Vascular changes in radiation bowel disease. Histopathology 1985; 9 (5) 517-534
  • 42 Fajardo LF. The pathology of ionizing radiation as defined by morphologic patterns. Acta Oncol 2005; 44 (1) 13-22
  • 43 Sheth S, Bleibel W, Thukral C , et al. Heightened NTPDase-1/CD39 expression and angiogenesis in radiation proctitis. Purinergic Signal 2009; 5 (3) 321-326
  • 44 Andreyev J. Gastrointestinal complications of pelvic radiotherapy: are they of any importance?. Gut 2005; 54 (8) 1051-1054
  • 45 Eifel PJ, Levenback C, Wharton JT, Oswald MJ. Time course and incidence of late complications in patients treated with radiation therapy for FIGO stage IB carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys 1995; 32 (5) 1289-1300
  • 46 Denham JW, O'Brien PC, Dunstan RH , et al. Is there more than one late radiation proctitis syndrome?. Radiother Oncol 1999; 51 (1) 43-53
  • 47 Wang CJ, Leung SW, Chen HC , et al. The correlation of acute toxicity and late rectal injury in radiotherapy for cervical carcinoma: evidence suggestive of consequential late effect (CQLE). Int J Radiat Oncol Biol Phys 1998; 40 (1) 85-91
  • 48 Dörr W, Hendry JH. Consequential late effects in normal tissues. Radiother Oncol 2001; 61 (3) 223-231
  • 49 Kennedy GD, Heise CP. Radiation colitis and proctitis. Clin Colon Rectal Surg 2007; 20 (1) 64-72
  • 50 Buchi K. Radiation proctitis: therapy and prognosis. JAMA 1991; 265 (9) 1180
  • 51 Cox JD, Stetz J, Pajak TF. Toxicity criteria of the radiation therapy oncology group (RTOG) and the european organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys 1995; 31 (5) 1341-1346
  • 52 Rubin P, Constine LS, Fajardo LF, Phillips TL, Wasserman TH. RTOG late effects working group overview late effects of normal tissues (LENT) scoring system. Int J Radiat Oncol Biol Phys 1995; 31 (5) 1041-1042
  • 53 Lund JÅ, Kaasa S, Wibe A, Widmark A, Fransson P. Late radiation effects to the rectum and anus after treatment for prostate cancer; validity of the LENT/SOMA score. Acta Oncol 2013; 52 (4) 727-735
  • 54 Common terminology criteria for adverse events. Version 4.3. Available at: http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf . Update June 14, 2010.
  • 55 Anseline PF, Lavery IC, Fazio VW, Jagelman DG, Weakley FL. Radiation injury of the rectum: evaluation of surgical treatment. Ann Surg 1981; 194 (6) 716-724
  • 56 Andreyev HJ, Vlavianos P, Blake P, Dearnaley D, Norman AR, Tait D. Gastrointestinal symptoms after pelvic radiotherapy: role for the gastroenterologist?. Int J Radiat Oncol Biol Phys 2005; 62 (5) 1464-1471
  • 57 Wachter S, Gerstner N, Goldner G, Pötzi R, Wambersie A, Pötter R. Endoscopic scoring of late rectal mucosal damage after conformal radiotherapy for prostatic carcinoma. Radiother Oncol 2000; 54 (1) 11-19
  • 58 Do NL, Nagle D, Poylin VY. Radiation proctitis: current strategies in management. Gastroenterol Res Pract 2011; 2011 (11) 917941
  • 59 Kochhar R, Patel F, Dhar A , et al. Radiation-induced proctosigmoiditis. Prospective, randomized, double-blind controlled trial of oral sulfasalazine plus rectal steroids versus rectal sucralfate. Dig Dis Sci 1991; 36 (1) 103-107
  • 60 Seo EH, Kim TO, Kim TG , et al. The efficacy of the combination therapy with oral and topical mesalazine for patients with the first episode of radiation proctitis. Dig Dis Sci 2011; 56 (9) 2672-2677
  • 61 Henriksson R, Franzén L, Littbrand B. Effects of sucralfate on acute and late bowel discomfort following radiotherapy of pelvic cancer. J Clin Oncol 1992; 10 (6) 969-975
  • 62 O'Brien PC, Franklin CI, Dear KB , et al. A phase III double-blind randomized study of rectal sucralfate suspension in the prevention of acute radiation proctitis. Radiother Oncol 1997; 45 (2) 117-123
  • 63 Kochhar R, Sriram PV, Sharma SC, Goel RC, Patel F. Natural history of late radiation proctosigmoiditis treated with topical sucralfate suspension. Dig Dis Sci 1999; 44 (5) 973-978
  • 64 Kennedy M, Bruninga K, Mutlu EA, Losurdo J, Choudhary S, Keshavarzian A. Successful and sustained treatment of chronic radiation proctitis with antioxidant vitamins E and C. Am J Gastroenterol 2001; 96 (4) 1080-1084
  • 65 Ehrenpreis ED, Jani A, Levitsky J, Ahn J, Hong J. A prospective, randomized, double-blind, placebo-controlled trial of retinol palmitate (vitamin A) for symptomatic chronic radiation proctopathy. Dis Colon Rectum 2005; 48 (1) 1-8
  • 66 Sarin A, Safar B. Management of radiation proctitis. Gastroenterol Clin North Am 2013; 42 (4) 913-925
  • 67 Pinto A, Fidalgo P, Cravo M , et al. Short chain fatty acids are effective in short-term treatment of chronic radiation proctitis: randomized, double-blind, controlled trial. Dis Colon Rectum 1999; 42 (6) 788-795 , discussion 795–796
  • 68 Talley NA, Chen F, King D, Jones M, Talley NJ. Short-chain fatty acids in the treatment of radiation proctitis: a randomized, double-blind, placebo-controlled, cross-over pilot trial. Dis Colon Rectum 1997; 40 (9) 1046-1050
  • 69 al-Sabbagh R, Sinicrope FA, Sellin JH, Shen Y, Roubein L. Evaluation of short-chain fatty acid enemas: treatment of radiation proctitis. Am J Gastroenterol 1996; 91 (9) 1814-1816
  • 70 Cavcić J, Turcić J, Martinac P , et al. Metronidazole in the treatment of chronic radiation proctitis: clinical trial. Croat Med J 2000; 41 (3) 314-318
  • 71 Sahakitrungruang C, Patiwongpaisarn A, Kanjanasilp P, Malakorn S, Atittharnsakul P. A randomized controlled trial comparing colonic irrigation and oral antibiotics administration versus 4% formalin application for treatment of hemorrhagic radiation proctitis. Dis Colon Rectum 2012; 55 (10) 1053-1058
  • 72 Khan AM, Birk JW, Anderson JC , et al. A prospective randomized placebo-controlled double-blinded pilot study of misoprostol rectal suppositories in the prevention of acute and chronic radiation proctitis symptoms in prostate cancer patients. Am J Gastroenterol 2000; 95 (8) 1961-1966
  • 73 Hille A, Schmidberger H, Hermann RM , et al. A phase III randomized placebo-controlled, double blind study of misoprostol rectal suppositories to prevent acute radiation proctitis in patient with prostate cancer. In J Radiat Oncol Biol Phys 2005; 63: 1488-1493
  • 74 Marx RE, Ehler WJ, Tayapongsak P, Pierce LW. Relationship of oxygen dose to angiogenesis induction in irradiated tissue. Am J Surg 1990; 160 (5) 519-524
  • 75 Clarke RE, Tenorio LM, Hussey JR , et al. Hyperbaric oxygen treatment of chronic refractory radiation proctitis: a randomized and controlled double-blind crossover trial with long-term follow-up. Int J Radiat Oncol Biol Phys 2008; 72 (1) 134-143
  • 76 Dall'Era MA, Hampson NB, Hsi RA, Madsen B, Corman JM. Hyperbaric oxygen therapy for radiation induced proctopathy in men treated for prostate cancer. J Urol 2006; 176 (1) 87-90
  • 77 Bennett MH, Feldmeier J, Hampson N, Smee R, Milross C. Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database Syst Rev 2012; 5 (5) CD005005
  • 78 Rubinstein E, Ibsen T, Rasmussen RB, Reimer E, Sørensen BL. Formalin treatment of radiation-induced hemorrhagic proctitis. Am J Gastroenterol 1986; 81 (1) 44-45
  • 79 de Parades V, Etienney I, Bauer P , et al. Formalin application in the treatment of chronic radiation-induced hemorrhagic proctitis—an effective but not risk-free procedure: a prospective study of 33 patients. Dis Colon Rectum 2005; 48 (8) 1535-1541
  • 80 Parikh S, Hughes C, Salvati EP , et al. Treatment of hemorrhagic radiation proctitis with 4 percent formalin. Dis Colon Rectum 2003; 46 (5) 596-600
  • 81 Luna-Pérez P, Rodríguez-Ramírez SE. Formalin instillation for refractory radiation-induced hemorrhagic proctitis. J Surg Oncol 2002; 80 (1) 41-44
  • 82 Haas EM, Bailey HR, Farragher I. Application of 10 percent formalin for the treatment of radiation-induced hemorrhagic proctitis. Dis Colon Rectum 2007; 50 (2) 213-217
  • 83 Triadafilopoulos G, Sarkisian M. Dilatation of radiation-induced sigmoid stricture using sequential Savary-Guilliard dilators. A combined radiologic-endoscopic approach. Dis Colon Rectum 1990; 33 (12) 1065-1067
  • 84 Viggiano TR, Zighelboim J, Ahlquist DA, Gostout CJ, Wang KK, Larson MV. Endoscopic Nd:YAG laser coagulation of bleeding from radiation proctopathy. Gastrointest Endosc 1993; 39 (4) 513-517
  • 85 Rustagi T, Mashimo H. Endoscopic management of chronic radiation proctitis. World J Gastroenterol 2011; 17 (41) 4554-4562
  • 86 Jensen DM, Machicado GA, Cheng S, Jensen ME, Jutabha R. A randomized prospective study of endoscopic bipolar electrocoagulation and heater probe treatment of chronic rectal bleeding from radiation telangiectasia. Gastrointest Endosc 1997; 45 (1) 20-25
  • 87 Tjandra JJ, Sengupta S. Argon plasma coagulation is an effective treatment for refractory hemorrhagic radiation proctitis. Dis Colon Rectum 2001; 44 (12) 1759-1765 , discussion 1771
  • 88 Taïeb S, Rolachon A, Cenni JC , et al. Effective use of argon plasma coagulation in the treatment of severe radiation proctitis. Dis Colon Rectum 2001; 44 (12) 1766-1771
  • 89 Zhou C, Adler DC, Becker L , et al. Effective treatment of chronic radiation proctitis using radiofrequency ablation. Therap Adv Gastroenterol 2009; 2 (3) 149-156
  • 90 Nikfarjam M, Faulx A, Laughinghouse M, Marks JM. Feasibility of radiofrequency ablation for the treatment of chronic radiation proctitis. Surg Innov 2010; 17 (2) 92-94
  • 91 Hou JK, Abudayyeh S, Shaib Y. Treatment of chronic radiation proctitis with cryoablation. Gastrointest Endosc 2011; 73 (2) 383-389
  • 92 Jao SW, Beart Jr RW, Gunderson LL. Surgical treatment of radiation injuries of the colon and rectum. Am J Surg 1986; 151 (2) 272-277
  • 93 Pricolo VE, Shellito PC. Surgery for radiation injury to the large intestine. Variables influencing outcome. Dis Colon Rectum 1994; 37 (7) 675-684
  • 94 Anseline PF, Lavery IC, Fazio VW, Jagelman DG, Weakley FL. Radiation injury of the rectum: evaluation of surgical treatment. Ann Surg 1981; 194 (6) 716-724
  • 95 Ayerdi J, Moinuddeen K, Loving A, Wiseman J, Deshmukh N. Diverting loop colostomy for the treatment of refractory gastrointestinal bleeding secondary to radiation proctitis. Mil Med 2001; 166 (12) 1091-1093
  • 96 Marks G, Mohiudden M. The surgical management of the radiation-injured intestine. Surg Clin North Am 1983; 63 (1) 81-96
  • 97 Lucarotti ME, Mountford RA, Bartolo DC. Surgical management of intestinal radiation injury. Dis Colon Rectum 1991; 34 (10) 865-869