Efficacy and safety of argon plasma coagulation for the treatment of hemorrhagic radiation proctitis

C. de la Serna Higuera, M. I. Martín Arribas, S. J. Rodríguez Gómez, A. Pérez Villoria, J. Martínez Moreno and A. Betancourt González

Unit of Digestive Diseases. Hospital Virgen de la Concha. Zamora, Spain

 

ABSTRACT

Objective: to evaluate the efficacy, safety and medium-/long-term clinical course of patients undergoing endoscopic treatment with argon plasma coagulation for hemorrhagic radiation proctopathy.
Design: descriptive, retrospective study with medium- and long-term follow-up.
Patients, material and methods: ten patients were treated with argon plasma coagulation for hemorrhagic radiation proctopathy between July 1998 and February 2003. Inclusion criteria were: evidence of chronic rectal bleeding, consistent endoscopic findings, and absence of any other cause of hematochezia after a comprehensive ano-rectal examination and complete colonoscopy. The equipment used was a standard colonoscope, an argon delivery unit, an argon plasma coagulation probe 1.5 mm in internal diameter, and a high-frequency electrosurgical generator. Consecutive treatment sessions were programmed whenever it was considered necessary until all mucosal lesions had been treated. Clinical and evolutive follow-up was performed with a focus on tolerance, efficacy, and potential argon plasma coagulation-related complications. Data were updated by personal or telephonic interview.
Results: in all patients, chronic rectal bleeding stopped after the last treatment session. The mean number of treatment sessions to stop symptoms was 1.7. Mean follow-up was 31.1 months. All sessions were well tolerated, similarly to standard rectoscopy. In one case a recurrence of rectal bleeding was observed four months later, which required two repeat sessions. Four patients were anemic at inclusion. Three of them reported a resolved anemia at the end of the study. No delayed argon plasma coagulation-related complications such us ulcers or strictures were seen.
Conclusions: argon plasma coagulation appears to be a useful, effective and safe treatment for rectal bleeding resulting from chronic radiation proctitis when compared to standard medical and endoscopic treatments. These successful outcomes seem to persist even after long-term follow-up.

Key words: Radiation proctitis. Rectal bleeding. Treatment. Argon plasma coagulation.

---

De la Serna Higuera C, Martín Arribas MI, Rodríguez Goacute;mez SJ, Pérez Villoria A, Martínez Moreno J, Betancourt González A. Efficacy and safety of argon plasma coagulation for the treatment of hemorrhagic radiation proctitis. A prospective study. Rev Esp Enferm Dig 2004; 96: 758-764.

---

Recibido: 04-04-03.
Aceptado: 02-03-04.

Correspondencia: C. de la Serna HIguera. Unidad de Digestivo. Hospital Virgen de la Concha. Avenida de Requejo, 31-33. 49002 Zamora. Teléf.: 980548 200. Fax: 980 548 221. e-mail: csernah@hotmail.com

 

INTRODUCTION

Radiation-induced proctopathy is a frequently-associated complication of radiotherapy for malignant pelvic tumors. Chronic radiation proctitis occurs-according to different case-series- up to 20% of patients receiving pelvic radiation, within a term which ranges between three months and thirty years after conclusion of the therapy (1-3). Radiation injury to the rectal wall becomes apparent like obliterative endarteritis with secondary tissue ischemic and development of neovascular mucosal lesions. These ones can bleed in a delayed fashion and different amounts: form little sporadic spotting which leads sometimes to chronic anemia state, to episodes of severe rectal bleeding (4).

Nowadays there are no clearly defined guidelines of treatment, in the absence of large controlled clinical trials (5). Surgical treatment must be carefully considered taking into account the high rate of surgery-associated morbi-mortality (3,6). On the other hand any other topical terapies initially used (sulfasalazine enemas, aminosalicylates and corticosteroid enemas ) have not been proved to have a role in the management of this condition ; so actually they are not advisable like single therapeutic option (5,7). In this clinical scenario another endoscopic treatments have been tested, some of them with encouraging outcomes: laser (8), bipolar electrocoagulation (9) and more reciently argon plasma coagulation (APC). APC is a non-touch electrocoagulation technique in which high-frequency alternating current can be delivered to the tissue by ionized gas. Several case-series reported until now (10-17), have demonstrated APC like effective, safe and low cost therapeutic alternative even after unsuccesful treatment using other methods.

We have not found Spanish series after bibliographic review (MEDLINE, EMBASE, Science Citation Index, Index Medicus Espantilde;ol 1997-2003). The aim of this study is to evaluate our results in CPA therapy of chronic rectal bleeding secondary to radiation proctitis taking account on clinical efficacy, potential secondary effects or clinical relapse after long-term follow-up.

PATIENTS, MATERIAL AND METHODS

Patients treated with APC for chronic rectal bleeding due to radiation-induced proctopathy between July 1998 and February 2003 were retrospectively analized. Colonoscopy to the cecum was performed in every patient to determine the severity of mucosal lesions and exclude other potential sources of bleeding. Only patients with active bleeding, normal examination of anus and rectum and no other potentially bleeding colonic lesions were included. Rectal byopses were taken to exclude other potential etiologies of proctitis. Ten patients were included (7 women, 3 men; median age 67.8 years; range 58 to 76 years). All patients had been previously treated with pelvic radiotherapy because uterine or prostate cancer (cervical cancer: 1 case; endometrial cancer: 6 cases, prostate cancer: 3 cases) within a range from 12 to 36 months. None of them had received any kind of specific treatment neither medical, surgical nor endoscopic. Three of the patients had laboratory data of normocytic, normochromic anemia. Three cases showed rectal telangiectasias circumscribed to the distal third of the rectum; in the other seven ones they were spread in clusters all over rectal mucosa. The equipment used were standard colonoscopes (Olympus CF 100 videoendoscope, conected to Olympus CV 100 videoprocessor) an APC equipment with APC probe with external diameter of 2 mm and internal diameter of 1.5 mm, argon delivery unit and high frequency surgery unit (ERBE Argon Plasma Coagulator ICC 200, ERBE Electromedizin, Tubingen, Germany). All patients were treated in an outpatient basis, with no antibiotic prophylaxis nor sedation. We used a technique incorporating only single point targeting with application time per point less than one second ("shots"). "Trawl-back" maneuvers were discarded because of the potential risk of mucosal ulcers or development of secondary stenosis as it is described in the literature review 5,17. The argon gas flow was set between 1.5 and 2 l/min at 60 W power, including aditional sessions until total endoscopic eradication of telangiectasic areas. All patients were followed in an outpatient basis. Finally, data were updated by telephone contact. Side effects and complications were defined as short-term if they appeared within 24 hours of the APC procedure.

RESULTS

A total of 19 treatment sessions were performed until endoscopically apparent coagulation of all telangiectasias (median for each patient: 1.9 sessions; range 1 to 4 sessions). The interval between sessions was 3-4 weeks. In 40% of the cases (4 patients) only one course of treatment was enough. Median follow up after APC treatment was finished was 31.8 months (range 10-45). There was significant improvement in rectal bleeding in all patients after treatment reported even after the first session. Nine of the 10 patients were completelly asymptomatic from last course of APC to the end of the study. Only one patient (number 4), (Table I) had recurrence of rectal bleeding 4 months later requiring two additional sessions. All sessions were well tolerated with symptomatology similar to standard rectoscopy. There were no short-term complications. Only in one case (number 8, woman, aged 70) (Table I) the patient developed tenesmus after completion of APC treatment; it lasted for three days resolving finally spontaneously. There were no symptoms compatible with major complications such us perforation, fistulas, ulcers or strictures. Three of four patients with parameters of normocitic-normochromic anemia before APC had normal haematological recounts when it finished, showing improvement of hemoglobin values in a range from 1.5 to 1.9 g/dl. One patient (number 4) was transfused 4 units of packed red blood cells, finally she was asymptomatic after four APC sessions.

DISCUSSION

Chronic radiation proctitis is the outcome of submucosal tissue injury induced by ionizing radiation to the rectal wall in patients treated for malignant pelvic neoplasms. Rectal bleeding is the main presenting complaint (4) with transient and scant hematochezia or severe rectal bleeding with analitical and -occasionally- hemodinamic disturbances which led to specific therapeutic management. Pharmacological agents used for this purpose until now (oral, topical or mixed) are often unsatisfactories, with partial recovery and short term relapses (5-7). Several case series have proved disappointing results with topical or oral sulfasalazine, 5 aminosalicylic acid and corticosteroids (5,18,19). Greater therapeutic success has been reported with topical formaldehyde (20) and topical or oral sucralfate (21,22); however they were all preliminary reports.

Development of new endoscopic procedures has led to a higher rate of therapeutic success and longer periods of symptomatic control. Both laser (8) and mono or bipolar electrocoagulation (9) have been considered to be the most effective methods of treatment for these patients (2,3,5). However both techniques are associated with potential morbidity derived from the difficulty of assessing the depth of the termal effect over the rectal wall. Argon plasma coagulation (APC) has been used in gastrointestinal endoscopy since 1994 (24). Three years later (10) were reported preliminary results about APC treatment of radiation-induced proctitis. The efficacy and safety of APC have been suggested in several case series (11-17). They have included from seven (11) to twenty eight patients (12), reaching a total amount of 110 patients treated in this setting. Therapeutic success was got in up to 95% of patients showing decreasing of transfusional requirements and improvement of anemia even after unsuccessful treatment using other conventional methods (12,15,16). Long-term complications of APC were exceptional (tenesmus or chronic, persistent diarrhoea (17) or developing of mucosal ulcers or rectal strictures attributed to "trawl back" or "painting" maneuvers. Safety of APC is associated with the limited depth of coagulation (2-3 mm); it explains the low risk of local perforation. We have not found Spanish series about this issue. Only case series of Luna-Pérez (21) and Fuentes (25) report results after treatment with heater probe and formalin enemas. Our retrospective study, in a similar way than previous international series, confirms that APC is a highly effective technic in symptomatic control of rectal bleeding (10 of the 10 patients; 100%). Hematochezia resolved after a single session of APC in 4 patients. Likewise, tolerance was excelent and argon gas flow rates and electrical power were lesser than ones used in other case series, in order to avoid potential complications (26). With the same aim the therapy was delivered using a technique of single point targeting less than one second per site. "Painting" of rectal wall was avoided because of tisular damage depends on total lenght of APC and total amount of energy delivered per area of rectal mucosa (17,27). Median follow up was higher than periods reported in another case series. This lead to conclusion that APC effects over rectal telangiectasias persists even after long term follow up. Kaasis et al. (13), Fantin et al. (11) and Villavicencio et al. (17) reported median follow up of 10 months. In our case series it lasted to 31.1 months after concluding CPA treatment, with 4 patients (1,3,5) (Table I) over 42 months.

The results in this study provide further data about the efficacy, safety and well-tolerance of APC in chronic rectal bleeding related to radiation proctopathy. These suitable results can be achieved early and stay for a long period of time after complete healing of rectal mucosa. APC appears to be an effective and safe method when gas flows and electrical power settings are in the ranges described and using "single-point" technique, with shots under one second. However, the scant number of patients included in our study and the retrospective design hinder us from drawing definitive conclusions. Further prospective, randomized trials with a longer number of patients are needed, comparing APC with other medical and endoscopic treatments. Likewise, longer case series are needed to settle optimal regimen of gas flow and electrical power, the most accurate technique of application and the minimum of damaged mucosa to treat in order to obtain persistent clinical remission (27). Meanwhile we consider that APC may be the first-choice technique in the treatment of rectal bleeding due to radiation proctitis, taking account its effectiveness, safety and low cost rather than different medical therapies of uncertain efficacy and other endoscopic approaches with more rate of potential complications and increased technical complexity in this setting.

REFERENCES

1. Glinsky NH, Burns DG, Barbezat GO, Lewin W, Myers HS, Marks IN. The natural history of radiation-induced proctosigmoiditis: an analysis of 88 patients. Q J Med 1983; 205: 40-53.        [ Links ]

2. Buchi K. Radiation proctitis: therapy and prognosis. JAMA 1991; 265: 1180-4.        [ Links ]

3. Babb RR. Radiation proctitis: a review. Am J Gastroenterol 1996; 91: 1309-11.        [ Links ]

4. Den Hartog FCA, van Haastert M, Batterman JJ, Tygat GNJ. The endoscopy spectrum of late radiation damage of the sigmoid colon. Endoscopy 1985; 17: 214-6.        [ Links ]

5. Bonis PA, Nostrant TT. Diagnosis and treatment of chronic radiation proctitis. UpToDate 2003; 11.1: CD 2.        [ Links ]

6. Marks G, Mohiudden M. The surgical management of the radiation-injured intestine. Surg Clin North Am 1983; 63: 81-6.        [ Links ]

7. Denton A, Forbes A, Andreyev J, Maher EJ. Non surgical interventions for late radiation proctitis in patients who have received radical radiotherapy to the pelvis (Cochrane Review). In: The Cochrane Library;1: 2003.Oxford: Update Software.        [ Links ]

8. Taylor JG, Di Sario JA, Buchi KN. Argon laser therapy for hemorrhagic radiation proctitis: long-term results. Gastrointest Endosc 1993; 39: 641-4.        [ Links ]

9. Jensen DM, Machicado JA, Cheng S, et al. A randomized prospective study of endoscopy bipolar electrocoagulation and heater probe treatment of chronic rectal bleeding from radiation telangiectasia. Gastrointest Endosc 1997; 45: 20-5.        [ Links ]

10. Chutkan R, Lipp A, Waye J. The plasma argon coagulator: a new and effective modality for treatment of radiation proctitis. Gastrointest Endosc 1997; 45: AB 27.        [ Links ]

11. Fantin AC, Binek J, Suter WR, Meyerberger C. Argon beam coagulation for treatment of symptomatic radiation-induced proctitis. Gastrointes Endosc 1999; 49: 515-8.        [ Links ]

12. Silva RA, Correia AJ, Moreia L, Lomba H, Lomba R. Argon plasma coagulation therapy for hemorrhagic radiation proctosigmoiditis. Gastrointest Endosc 1999; 50 (2): 221-4.        [ Links ]

13. Kaasis M, Oberti F, Burtin P, Boyer J. Plasma coagulation for the treatment of hemorrhagic radiation proctitis. Endoscopy 2000; 32: 673-6.        [ Links ]

14. Tam W, Moore J, Schoeman M. Treatment of radiation proctitis with argon plasma coagulation. Endoscopy 2000; 32: 667-72.        [ Links ]

15. Tjandra JJ, Sensupta S. Argon plasma coagulation is an effective treatment for refractory hemorrhagic radiation proctopathy. Dis Colon Rectum 2001; 44: 1759-65.        [ Links ]

16. Taieb S, Rolachon A, Cenni JC, Nancey S, et al. Effective use of argon plasma coagulation in the treatment of severe radiation proctitis. Dis Colon Rectum 2001; 44: 1766-71.        [ Links ]

17. Villavicencio RT, Rex DK, Rahmani E. Efficacy and complications of argon plasma coagulation for hematochezia related to radiation proctopathy. Gastrointest Endosc 2002; 55: 70-4.        [ Links ]

18. Baum CA, Biddle WL, Minner PB, Jr. Failure of 5-aminosalicylic acid enemas to improve chronic radiation proctitis. Dig Dis Sci 1989; 34: 758-69.        [ Links ]

19. Baughan CA, Canney PA, Buchanan RB, Pickering RM. A randomised trial to assess the efficacy of 5-aminosalicylic acid for the prevention of radiation enteritis. Clin Oncol 1993; 5: 19-24.        [ Links ]

20. Seow-Choen F, Goh HS, Ew KW, et al. A simple and effective treatment for hemorrhagic radiation proctitis using formalin. Dis Colon Rectum 1993; 36: 135-8.        [ Links ]

21. Luna-Pérez P, Rodríguez-Ramírez SE. Formalin instillation for refractory radiation-induced hemorrhagic proctitis. J Surg Oncol 2002; 80: 41-4.        [ Links ]

22. Kochhar R, Sharma SC, Gupta BB, Metha SK. Rectal sucralfate in radiation proctitis. Lancet 1988; 2: 400.        [ Links ]

23. Kochhar R, Srivam DVJ, Sharma SC, et al. Natural history of late radiation proctosigmoiditis treated with topical sucralfate suspension. Dig Dis Sci 1999; 44: 973-8.        [ Links ]

24. Farin G, Grund KE. Technology of argon plasma coagulation with particular regard to endoscopic applications. Endosc Surg 1994; 2: 71-7.        [ Links ]

25. Fuentes D, Monserrat R, Isern AM, et al. Colitis due to radiation: endoscopic management with heat probe. Gen 1993; 47: 165-7.        [ Links ]

26. Saurin JC, Cohelo J, Lepetre J. Argon plasma coagulation efficiently controls bleeding in patients with watermelon stomach or radiation proctitis (abstract). Gastrointest Endosc 1999; 49: AB 169.        [ Links ]

27. Lee J. Radiation proctitis: a niche for the argon plasma coagulator. Gastrointest Endosc 2002; 56: 779-81.        [ Links ]