Intrarectal formalin, radiation proctitis, treatment
Brij Sharma,1, 2 Ramesh Kumar,1 Kumar Kirti Singh,1 Vivek Chauhan2
*Department of Gastroenterology & Human Nutrition,
All India Institute of Medical Science,
*Department of Medicine,
Indira Gandhi Medical College
Dr. Brij Sharma
Background: Chronic radiation proctitis is known to be a difficult to treat condition. Argon Plasma Coagulation (APC) though being effective requires prolonged sessions and has limited availability. Formalin, by virtue of its chemical cauterizing effects, has been found to be effective in patients with bleeding radiation cystitis and hemorrhagic proctitis. Our goal was to study the effectiveness of 4% formalin instillation in resistant patients of chronic hemorrhagic radiation proctitis.
Methods: 13 patients with chronic radiation proctitis were treated with instillation of 50 ml 4% formalin into the rectum (3 minutes for 3 times). The total mucosal contact time was approximately 10 minutes. Their clinical response, tolerance to treatment and complications were assessed. Patients who did not have complete response were given another session(s) a week later.
Results: The mean (SD) age of patients was 48.62±11.66 years. Twelve patients (92%) were female who received radiotherapy for carcinoma cervix and 1(08%) was male with carcinoma prostate. The overall clinical response rate was 100%; eight patients (61.5%) had complete cessation of bleeding while 5 patients (38.5%) had significant cessation of bleeding. Eight patients needed only one session, four needed 2 sessions and one patient needed 3 sessions for the clinical response. Serious complications were not observed. No recurrence of symptoms was seen during follow-up
Conclusion: The treatment of hemorrhagic radiation proctitis with local formalin instillation is effective, well tolerated, inexpensive, technically simple and safe procedure.
Radiation therapy is a common treatment modality for pelvic malignancies. Radiation proctitis is a troublesome complication of radiation therapy. The fixed location of rectum and proximity to treatment port makes it vulnerable to the radiation injury[1,2]. Radiation proctitis is characterized by development of multiple peticheal and telangiectatic spots along with ulcers in the rectum. Clinically, patients present with bleeding per rectum, mucous discharge, pain and diarrhoea. Although the acute radiation proctitis occurs in as many as 75% of irradiated patients, it is mostly self- imiting. The chronic radiation proctitis which is more associated with refractory rectal bleeding occurs in 2.5 – 30% of irradiated patients[4,5,6]. This condition is both physically debilitating and socially inconvenient .
Primary treatment of radiation proctitis is medical and includes low residue diet, laxatives and retention enemas with steroids, sucralfate or sulfasalazine.[8,9,10] However, these treatment modalities have not been proved to be effective in most cases of chronic hemorrhagic radiation proctitis[11,12]. Argon plasma and Laser coagulation (APC) has been found effective treatment, but it is time-consuming, requires multiple sessions and is not available at most centers[13,14]. Moreover, diversion colostomy is frequently ineffective and resection or excision of the rectum carries a considerable risk with a high morbidity and mortality[15,16]. Rectal instillation of 4% formalin solution has been used by several workers to control severe or refractory bleeding from radiation proctitis with encouraging results[17,18,19,20,21,22].
Patients and methods
This is a prospective study. Between January 2005 and February 2009, 13 patients of chronic and refractory, hemorrhagic radiation proctitis were enrolled from two centers: Indira Gandhi Medical College, Shimla and All India Institute of Medical Science, New Delhi. All patients had failed treatment with either retention enemas (10 patients) or APC (3 patients). Nine patients required repeated blood transfusion to maintain hematocrit. All patients had hemorrhagic proctitis at the time of inclusion into the study. Their severity of disease was graded according to frequency of bleeding and endoscopic findings (Table 1).
Bowel preparation was done in all patients, 4 hours prior to procedure, with 137.15 grams of Polythylene glycol powder (PEGLEC, Tablets – India Limited) dissolved in 2 liters of water. The procedure was done under light sedation with combination of intravenous pentazocine (15 mg) and promethazine (25mg). Patients were positioned left lateral or prone. Lignocaine jelly was applied around perianal region and a colonoscope was inserted till the proximal margin of diseased segment. Subsequently, 50 ml of 4% formalin solution was loaded in a syringe and slowly pored through the water channel of the scope. While doing so, the scope was gradually rotated and withdrawn in order to ensure the smearing of involved mucosa with formalin. The solution was suctioned after 3 minutes and saline irrigation was done. The perineum was protected with drapes to prevent spillage. The same procedure was repeated 3 times in one session. The total mucosal contact time was approximately 9-10 minutes. Each patient was observed for 4 hours after the procedure before discharge for complications. All patients were treated on outpatient basis.
Each patient was followed up weekly till they became symptom free. Another follow-up was done about 3 months after the last procedure, with further follow-up as needed. During follow-up patients were assessed with regard to bleeding symptoms, tolerance to procedure and complications. Hemoglobin levels were measured and subjective quantification of blood loss was done. Patients who did not have complete response were offered to receive another session of formalin application after a week.
Refractory proctitis – failing to respond to treatment with either retention enemas or APC.
Complete response – No further episodes of bleeding after one session( three applications) of formalin
Significant response – Cessation of >75% bleed ( subjective patient assessment) after one session (three applications) of formalin.
Failed response – Bleeding continued despite one session (three applications) of formalin. Serious side effects– rectal perforation, fistulization, stricture formation, chronic rectal ulcer, incontinence or systemic toxicities.
This study included 13 patients with chronic hemorrhagic radiation proctitis unresponsive to conventional medicaltreatments. The mean (SD) age of patients was 48.62±11.66 years while median (range) was 50 (24-70) years. 92%(12) of study population was females receiving radiotherapy for carcinoma cervix and 8% (one) male patient receiving radiotherapy for carcinoma of prostrate. Ten patients had received only external beam radiation therapy while three patients received radiation from both intracavitary and external techniques. A summary of patient’s demographic and clinical characteristics is mentioned in the Table 2. Median (range) duration of rectal bleeding was 3 (1-6) months at presentation. Majority of patients had severe disease at presentation (grade II in 61.5% and grade III in 31%) and 9 required multiple blood transfusions (2-6 units)prior to formalin therapy The follow-up ranged from 3 to 12 months (median 7 months). During the follow up one patient died from advanced disseminated malignancy. None of them had recurrence of rectal bleeding.
Overall, 8 patients (61.5%) had complete response. Remaining 5 (38.5%) patients had significant response of which 4 patients required two sessions and one patient required three sessions of formalin application. None of the patients had failed response. Following procedure, none of the patients needed blood transfusion to maintain hematocrit. All patients tolerated the procedure well. Apart from short period of perianal pain, none of the patients developed any serious side effects.
Treatment of chronic radiation proctitis is difficult and frustrating. Numerous treatment modalities which include steroids, aminosalicyclic acid, fatty acids or sucralfate enemas have had only limited success[11,12]. APC continues to be an important option, but is associated with local complications, requirement of prolonged sessions and has a limited availability[13,14,32]. The pathological lesions responsible for the bleeding in radiation proctitis are mainly telangiectasias. Therefore, the main therapeutic aim is to occlude these lesions. Formalin has been found to have chemical cauterizing action. It causes precipitation of cellular protein and occlusion of telangiectatic lesions and small capillaries. The use of formalin in the management of radiation proctitis emerged from its use in the treatment of bleeding radiation cystitis. In 1986, Rubinstein et al. successfully used a rectal wash with formalin for the first time in the treatment of radiation proctitis. After these results, many authors initiated treatments of hemorrhagic radiation proctitis with formalin. In this study, we have presented our experience with local formalin therapy for hemorrhagic radiation proctitis unresponsive to conventional medical treatments.
In the present study, we have treated 13 patients with chronic hemorrhagic radiation proctitis with instillation of 4% formalin. The overall success rate was 100%, with complete response in 8 patients (61.5%) and significant response in 5 (38.5%) patients. The response rate is comparable to that of previous studies[18,19,20,21,22,23]. Some of the published reports of use of formalin in the treatment of radiation proctitis are mentioned in Table 3.
Our method of application of formalin was different. In fact, various techniques have been used by different investigators: like irrigation of rectum with large volume (2 liters) formalin for 15 minutes, insertion of formalin- oaked gauze for 2-3 minutes, repeated instillation of aliquots of 50 ml formalin for 30 seconds (total volume 400-500 ml). We have used repeated instillation small volume (50 ml) 4% formalin for 3 minutes each time, amounting to a total exposure of maximum 150 ml for about 10 minutes per session.
The concentration of formalin optimal for the procedure is unknown. A varied concentration of formalin ranging from 2% to 10% has been used[17,18,22,25,26[. However, a 4% concentration has been used most widely. A lower concentration may be safer but is associated with lower response rate. In a study where 2% formalin was used; the overall response rate was 78.2%, while the complete success rate was only 47.5%. Even the use of 10% formalin has resulted in overall success rate of 93% which is comparable to 4% formalin where success rate ranged from 70% to 100% have been reported[18,19,20,21,22]. Further, a higher concentration of formalin may result in higher incidence of complications. We have used 4% formalin with a success rate of 100%.
All of our patients were treated on outpatient basis and discharged 4 hours after the procedure. The procedure was tolerated well by all patients under light sedation. In the earlier studies, the procedure has been done under general or regional anesthesia[20,27]. None of our patients developed any serious side effects. Several published reports have also shown no serious complications of local formalin therapy[19,20,22]. However, a higher incidence of local complications (rectal ulcers and strictures) has been reported by de Parades et al (Table 3). This may not be entirely due to formalin, as a higher proportion (36%) of patients in this case series had ano-rectal malignancy.
In this study, we have documented a very good response to 4% formalin therapy in patients with refractory radiation proctitis who would otherwise have required a surgical treatment. It is known that surgery in irradiated tissues is associated with various complications like anastomotic leak, fistulization and pelvic sepsis. Further, a fecal diversion mostly fails to stop bleeding[28,29,30,,31]. Formalin usually causes cessations of bleeding in a short period of time. Eight of 13 patients in our study needed only one session, 4 patients needed 2 sessions and only one patient needed 3 sessions. This is a major advantage of formalin treatment over APC. In a study whereAPC was the modality of treatment, the median number of sessions of APC requirement was 3 initially while 71% required maintenance therapy for 7 months.
In conclusion, the treatment of hemorrhagic radiation proctitis with local formalin instillation is effective, well tolerated and safe procedure. The procedure is inexpensive, technically simple and can be done on an outpatient basis. We report a clinical response rate of 100% without any serious side effects. Therefore, we suggest that 4% formalin treatment should be offered to all patients with chronic hemorrhagic radiation proctitis. In a resource poor country, it may be used as first line treatment in such patients.
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