Joint Hospital Surgical Grand Round Radiation Proctitis

1. Joint Hospital Surgical Grand Round Radiation Proctitis MF HO Yan Chai Hospital 20/4/2013

2. Background • Frequently observed after treatment of pelvic tumour, e.g. CA prostate, CA cervix • Due to microvascular injury and disruption of mucosal blood flow • Neovascularization plays a role • Severity related to total dose, dose frequency, area of exposure, source geometry • Acute vs Chronic radiation change

3. Complications associated with of pelvic irradiation • Proctitis • Ulceration • Stricture • Incontinence • Fistula formation

4. Presentation • Fever • Rectal pain • Tenesmus • Constipation / diarrhoea • Mucus passage • PR bleeding • Fistula formation

5. Clinical assessment • Subject symptoms • Bleeding, diarrhoea, tenesmus, pain, incontinence • Physical examination • Rectal telangiectasia, ulceration, stricture • Endoscopic assessment • Endoscopy, endorectal ultrasound • Functional assessment: • Anal manometry, defaecatory proctogram

6. Grading of severity • LENT – SOMA ( Late Effect Normal Tissue – Subjective Objective Management Analysis) Scale • National Cancer Institute Common Toxicity Criteria for Adverse Event Version 4 • Various grading system employed across different studies • Frequency of symptoms and requirement of intervention

9. Incidence • Varies due to different classification system • Varies due to different scheme of RT use1 • External beam irradiation : 8-39% • Brachytherapy: 8-13% • Combine 8-21% • May increase if patient has concomitant inflammatory bowel disease2 • Nhue L. Do et al. Radiation proctitis: Current Strategies in management. Gastroenterology Research and Practice. Volume 2011. • C.G. Wilet et al. Acute and late toxicity of patients with inflammatory bowel disease undergoing irradiation for abdominal and pelvic neoplasms. Int J Rad Onc Bio Phy. Vol 46, No. 4 pp 995-998, 2000

10. Management strategy • Topical treatment • Oral medications • Endoscopic treatment • Hyperbaric oxygen • Surgical intervention

11. Topic treatment • Sulcrafate • Mesalazine • Prednisolone / Hydrocortisone • Misoprostol • Short chain fatty acid enema • Formalin dab / instillation

12. Topic treatment • Advantages • Easy to apply, patient directed • Minimal complications • Disadvantages • Limited efficacy • Studies using combination of oral and topical agents • Relieve mainly bleeding symptoms

13. Formalin • Advantages • Higher efficacy1 • Ablative effect by protein hydrolysis • Disadvantages • Office procedure • Further injury to rectal mucosa • Higher complication rate: anal pain, tenesmus, fever, diarrhoea • Known Human carcinogen - WHO International Agency for Research on Cancer (IARC) 1. V.P. Nelamangala Ramakrishnaiah et al. Colorectal Disease 2012, Vol 14, 876-882.

14. Ref: V.P. Nelamangala Ramakrishnaiah et al. Colorectal Disease 2012, Vol 14, 876-882.

15. Oral medications • Aminosalicylic acid • Transamin • Vitamin A / C • Antibiotics • Laxatives • Part of standard care • Usually combined with other modalities of treatment • Not useful in acute situations

16. Endoscopic treatment • Argon plasma coagulation • Cryotherapy • Radiofrequency ablation • Laser therapy • Heater probe • Formalin dab / irrigation

17. Argon plasma coagulation • Superficial ablative therapy – limited penetration • Useful in acute setting – haemostasis • Allow assessment and treatment in same session • Less local side effect compared with Formalin • Not for “ultra-low” lesion • Colonic perforation has been reported

18. Argon plasma coagulation • Karamanolis et al. Endoscopy 2009. • 56 patients with radiation proctitis treated with APC • Average treatment session of 2 • 6/56 patients failed to response (extent of telangiectasia and anaemia) • 38 patients followed > 1 yr • 24/38 (63% has no further bleeding symptoms) • Non comparative study • High drop out rate

19. Argon plasma coagulation • Alfadhli et al. Cancer J Gastroenterology 2008. • 22 patients treated with APC and /or formalin • 11 APC, 8 formalin, 3 APC + formalin • Anaemia responded in : • 11/14 patients with APC • 7/11 patient with formalin • Side effects more prominent in formalin group (9 in formalin vs 2 in APC) • Only comparative study available • Overlapping treatment without intention to treat analysis • Small group of patients • Highlighted lower in side effect in APC group

20. Hyperbaric oxygen (HBO) • Treatment of choice in refractory radiation proctitis before consideration of surgery • NNT = 31 • Satisfactory response in documented series • Limited access • Risks of barotrauma / oxygen toxicity 1. R.E. Clake et al. Hyperbaric oxygen treatment of chronic refectory radiation proctitis: A randomized and controlled double blind crossover trial with long term follow up. Int J Rad Onc Bio Phy. Vol 72, No.1. pp 134-143, 2008.

21. Surgical intervention • Refractory bleeding • Complete obstruction • Fistula / abscess formation • Proctectomy +/- proximal diversion colostomy • Proximal diversion colostomy • Perineal procedures

23. Comparing 50 patients with radiation proctitis using formalin dab vs tap water irrigation and antibiotics treatment from 2010 to 2012 • Patients with other complications from radiation e.g. fistula, rectal ulcers, strictures were excluded • Patient was assessed 8 weeks after treatment • Symptoms, satisfaction, sigmoidoscopy findings

25. Results

26. Randomized study • Comparing new treatment with current standard of treatment • Additional advantage of treating post irritation constipation

27. Symptoms severity before treatment was not compared • ? Difference in baseline symptoms severity • Results are not presented well • ? Why comparing difference of difference between 2 treatment groups • Irrigation was given with antibiotics • Cannot distinguish treatment effect from irrigation / antibiotics • Short duration of follow up • RT change delay up to 2 years after RT

28. Conclusion • Radiation proctitis is commonly encountered as radiotherapy to pelvis is increasingly used • Topical and oral medication are more of maintenance therapy • Acute bleeding can be dealt with ablative therapy • Hyperbaric oxygen can be employed in refractory case • Surgery is the last resort, risks needed to be considered

29. Reference • Management of Radiation Proctitis. William M . Mendenhall et al. American Journal of Clinical Oncology, 2012. • A randomized controlled trial comparing colonic irrigation and oral antibiotics administration versus 4% formalin application for treatment of haemorrhagic radiation proctitis. Chucheep Sahakitrungruang et al. Dis Colon rectum 2012; 55: 1053-1058. • Endoscopic and medical therapy for chronic radiation proctopathy: a systematic review. Brian Hanson et at. Dis Colon Rectum 2012; 55: 1081-1095 • Nhue L. Do et al. Radiation proctitis: Current Strategies in management. Gastroenterology Research and Practice. Volume 2011. • C. G. Wilet et al. Acute and late toxicity of patients with inflammatory bowel disease undergoing irradiation for abdominal and pelvic neoplasms. Int J Rad Onc Bio Phy. Vol 46, No. 4 pp 995-998, 2000 • V.P. Nelamangala Ramakrishnaiah et al. Colorectal Disease 2012, Vol 14, 876-882. • Alfadhli et al. Efficacy of argon plasma coagulation compared to topical formalin application for chronic radiation proctopathy. Cancer J Gastroenterology 2008. • Karamanolis et al. Argon plasma coagulation has a long-lasting therapeutic effect in patients with chronic radiation proctitis. Endoscopy 2009. • R.E. Clake et al. Hyperbaric oxygen treatment of chronic refectory radiation proctitis: A randomized and controlled double blind crossover trial with long term follow up. Int J Rad Onc Bio Phy. Vol 72, No.1. pp 134-143, 2008