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Year : 2019  |  Volume : 15  |  Issue : 1  |  Page : 92-95

Four percent formalin application for the management of radiation proctitis in carcinoma cervix patients: An effective, safe, and economical practice

1 Department of Gastroenterology, IGMC, Shimla, Himachal Pradesh, India
2 Department of Radiotherapy, Cancer Hospital, IGMC, Shimla, Himachal Pradesh, India
3 Department of Anatomy, IGMC, Shimla, Himachal Pradesh, India
4 Department of Physiology, IGMC, Shimla, Himachal Pradesh, India
5 Department of Radiotherapy, IGMC, Shimla, Himachal Pradesh, India
6 Department of Microbiology, IGMC, Shimla, Himachal Pradesh, India

Date of Web Publication13-Mar-2019

Correspondence Address:
Dr. Manish Gupta
Department of Radiotherapy, Cancer Hospital, IGMC, Shimla, Himachal Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_393_17

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 > Abstract 

Context: Radiotherapy is a very effective treatment modality for pelvic malignancies such as carcinoma of the cervix. However, it is quite common for chronic radiation proctitis (CRP) to manifest after radical radiotherapy. CRP is a source of significant morbidity, and there is a lack of effective treatment modalities. There also exists a general lack of guidelines on management of CRP.
Aims: To assess the benefit from 4% formalin application for the treatment of Grade >2 CRP among patients previously treated with radical radiotherapy for cervical carcinoma.
Settings and Design: This retrospective descriptive study involved 29 eligible patients who were treated from November 2010 - November 2015 for CRP with 4% formalin application.
Materials and Methods: Of the 1864 patients of carcinoma cervix treated during the said patients, 29 patients fulfilled the eligibility criteria. Eligible patients were invited telephonically for follow-up and were assessed for response and complications of the procedure.
Results: 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. 62% patients had complete freedom from rectal bleed, while 34.5% patients had partial benefit. Only one patient required diversion colostomy for persistent bleeding.

Keywords: 4% formalin, carcinoma cervix, radiation proctitis

How to cite this article:
Sharma B, Gupta M, Sharma R, Gupta A, Sharma N, Sharma M, Sharma V, Vats S, Gupta M, Seam RK. Four percent formalin application for the management of radiation proctitis in carcinoma cervix patients: An effective, safe, and economical practice. J Can Res Ther 2019;15:92-5

How to cite this URL:
Sharma B, Gupta M, Sharma R, Gupta A, Sharma N, Sharma M, Sharma V, Vats S, Gupta M, Seam RK. Four percent formalin application for the management of radiation proctitis in carcinoma cervix patients: An effective, safe, and economical practice. J Can Res Ther [serial online] 2019 [cited 2020 Jul 12];15:92-5. Available from: http://www.cancerjournal.net/text.asp?2019/15/1/92/244459

 > Introduction Top

Radiotherapy (RT) is a very effective treatment modality for pelvic malignancies such as those involving the uterine cervix. The use of radical doses of radiation leads to a significant proportion of patients being cured. However, such high doses also cause the development of significant late toxicities among long-term survivors.[1]

Chronic radiation proctopathy (CRP) is one of the most bothersome late toxicities among patients treated with radical pelvic RT. Incidence is reported to be as high as 20%. CRP could occur either as a continuation of acute symptoms 3 months after the completion of RT or symptoms that begin 3 months after the initiation of RT. The median onset is 8–12 months, but onset can occur as late as 30 years.[2] Common symptoms include diarrhea, tenesmus, mucus/blood per rectum, urgency, incontinence, and pain. The complaint of most concern would be rectal bleeding.[3]

There is a general agreement that the incidence is likely related to the dose of radiation, area of the exposure method of delivery, and intrinsic radiosensitivity. The standard treatment for locally advanced carcinoma of the cervix involves the delivery of doses through both external beam and brachytherapy. While the external beam component delivers about 45–50 Gray (Gy) (), brachytherapy is utilized to escalate dose to about 90 Gy to the Point A. While the external beam component delivers a significant dose to the rectum, the brachytherapy component too delivers a smaller but definite contribution to rectal dose. While such high doses correlate with high cure rates, it is unfortunately associated with a significant proportion of survivors suffering from CRP.[4]

Despite being a very common complication, very sparse literature exists in regards to the management of CRP. Since carcinoma of cervix is predominantly a disease of low-middle income countries such as India, a significant proportion of patients are treated with non-conformal RT techniques, which are associated with higher rectal toxicities in comparison to patients treated with intensity-modulated RT (IMRT).

Since our institute has been utilizing formalin instillation to treat CRP since 2010, we recognized a unique retrospective opportunity to describe the effectiveness of this simple and economical technique.

 > Subjects and Methods Top

We did a retrospective analysis of the patients who had received formalin application for the treatment of CRP after prior RT for carcinoma cervix from November 2010 to November 2015. The hospital records of all cervical carcinoma patients treated during the said period were screened to find patients matching the inclusion criteria [Table 1]. Of the 1864 patients of carcinoma of the cervix treated during the mentioned period, 29 patients (matching the inclusion criteria) were found to have taken treatment with formalin application for CRP [Table 2]. At the time of the retrospective analysis, each of the 29 patients was contacted through telephonic invitation for a visit, and informed consent for the study was obtained.
Table 1: Inclusion and exclusion criteria

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Table 2: Baseline characteristics of patients with chronic radiation proctitis

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The patients had initially used to be on follow-up in the RT department and then had been referred to the gastroenterology department where they were taken up for colonoscopy. After a diagnosis of CRP, the severity of disease was graded according to the frequency of bleeding and endoscopic findings [Grading as per [Table 3].[5]
Table 3: Grade of chronic radiation proctitis

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These patients had been planned for formalin application. Bowel preparation was done in all patients, 4 h before procedure, with 137.15 g of Polyethylene glycol powder (PEGLEC, Tablets – India Ltd.) dissolved in 2 L of water. The procedure was done under light sedation with a combination of intravenous pentazocine (15 mg) and promethazine (25 mg). 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 to ensure the smearing of involved mucosa with formalin. The solution was suctioned after 3 min 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 min. Each patient was observed for 4 h after the procedure before discharge for complications. All patients were treated on outpatient basis. These were then followed up monthly. Further applications were planned in patients, who were still having symptoms after a gap of 4 weeks. Maximum of three applications were done at an interval of 4 weeks each.

 > Results Top

This retrospective descriptive analysis involves 29 patients (female patients of cervical cancer) who had been treated with RT. The median age of patients was 50 years. All these patients had been initially treated with external beam RT and/or intracavity brachytherapy. All of these patients had initially been treated conservatively for CRP first in the form of steroid retention enema but when no clinical improvement was observed, were referred to gastroenterology department for assessment and 4% formalin instillation. The mean duration of time from the completion of RT to onset of bleeding per rectum was 13 months (ranging from 5 to 27 months).

Twenty patients had anemia on presentation and fifteen of these patients had received prior blood transfusions. Formalin application had been taken up after a median of 17 months of completion of RT. The presenting symptom in all of these patients had been bleeding per rectum. In seven patients tenesmus and diarrhea were also associated. One patient had complained of rectal discharge and one of the pain perianal regions along with bleeding per rectum. One patient was on anticoagulants for deep vein thrombosis. The median follow-up of patients (calculated from the completion of treatment to the last follow-up) was 17 months (ranging from 1 month to 24 months).

In eight patients, bleeding had subsided after a single application of formalin. Nineteen patients required two applications to control their symptoms. Two patients had required three applications of formalin [Figure 1]. No significant side effects of the treatment had been reported.
Figure 1: Colonoscopic image of a chronic radiation proctitis patient on follow-up after 4% formalin application

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At the latest follow-up, 62% (n = 18) of these patients had reported complete cessation of their bleeding. A further 34.5% (n = 10) of patients had reported intermittent mild bleeding, which was a decrease from the baseline [Figure 2]. Only one patient had to be taken up for diversion colostomy for uncontrolled bleeding.
Figure 2: Colonoscopic image showing chronic radiation proctitis with blood oozing

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The application of 4% formalin per se was not associated with any complication whatsoever.

 > Discussion Top

Radiation proctitis is generally of two types, defined as acute or chronic as per their temporal onset. Acute radiation proctitis is an early adverse effect of RT, and it occurs during and up to 3 months after completion of pelvic RT. Acute radiation proctitis is related to radiation-induced cell loss in the superficial rectal mucosa, and it usually subsides after cellular turnover replaces the epithelium. CRP is distinctly different from acute radiation proctitis in that it is a late effect of radiation. Although symptoms may overlap with acute radiation proctitis, CRP has a different underlying pathogenesis. The pathology underlying CRP involves vascular changes which could lead to ischemia, fibrosis, and bleeding. Grossly, it is common to observe telangiectasia, strictures, ulcerations, and fistula. Microscopically, focal distortion of small arterioles and vascular intimal fibrosis can be seen.[6],[7],[8]

In low- and middle-income countries such as India, there is a very large burden of cervical carcinoma. A majority of patients are treated with conventional RT which is associated with much higher toxicity to normal tissues in comparison to conformal RT techniques such as IMRT. External beam radiation studies have seen incidence rates of radiation proctitis range from 2% to 39% depending on the severity/grade of proctitis, whereas IMRT studies have seen incidence rates from 1% to 9%.[9]

While CRP could cause a constellation of symptoms such as tenesmus, diarrhea, constipation, and bleeding, the most clinically troublesome feature happens to be bleeding. As anemia is an established problem in Indian patients due to nutritional factors CRP could exacerbate it to severe extents. It is not uncommon for patients with CRP to present with severe anemia requiring multiple blood transfusions. While Grade-1 CRP can be treated with medications including sucralfate, antidiarrheals, steroid enema, and hyperbaric oxygen, it is to be noted that Grade ≥2 CRP seldom responds to these.[10],[11]

While no large randomized studies exist, it can be mentioned that techniques such as argon plasma coagulation (APC), yttrium aluminum garnet (YAG)-laser coagulations and formalin applications are described to be of benefit in small retrospective studies. While studies involving APC and YAG-laser coagulation report reasonable success rates, the studies do concede that some patients' symptoms remain refractory and that the procedures involve definite risk of bowel injury. Further, these techniques involve the use of expensive equipment.[12]

In contrast to APC and YAG-laser coagulation, the use of formalin application for CRP involves negligible expense. The biological rationale happens to be the fact that formalin seals radiation-induced telangiectatic neovasculature in radiation-damaged tissues through a process of chemical cauterization. Reported success rates range from 60% to 100% in various reports.[13],[14],[15],[16] While studies have utilized formalin application with concentrations ranging from 3.6% to 10%, it must be noted that lower concentrations were as efficacious as higher concentrations, while also being associated with lesser toxicities. Reported toxicity in literature includes acute colitis, which is usually transient.[17]

The only other alternative in addition to the above-mentioned techniques involves surgical resection of the bleeding site. This may involve a resection-anastomosis, and may at times warrant the creation of a diversion colostomy. In view of the obvious morbidity, surgical techniques are usually reserved for patients not responding to endoscopic techniques such as APC, YAG-laser coagulation, and formalin application.[6],[18]

The current study involves the use of 4% formalin application to foci of intrarectal telangiectasia. While a few patients responded as early as after the first application, a further few patients responded satisfactorily after one or two more applications. Only one patient did not enjoy any response and had to undergo surgical resection and diversion colostomy. Overall, no incidence of procedure-related toxicity was observed.

This being a retrospective study involving patients from a single institution, we have to acknowledge a few shortcomings. While we cannot claim that our results are universally generalizable, we can reasonably state that these observations can validate a future prospective study utilizing 4% formalin application for the treatment of CRP. This is, in fact, a need of the hour given that a large number of patients are treated with conventional pelvic RT for cervical carcinoma in low- and middle-income countries. Given that a considerable proportion of these patients become long-term survivors, these patients are likely to suffer from CRP, and consequences of anemia due to blood loss. Our experience with the use of 4% formalin has been very effective with an overall response rate exceeding 90% without any serious adverse effects.

With the observations in the study, it can be claimed that 4% formalin application can be a safe, effective and economical alternative to APC and YAG-laser coagulation. The low-cost and easy availability of 4% formalin adds to the attractiveness of this technique, especially for first-line treatment in resource-poor countries as an alternative to more expensive or more morbid alternatives.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

Swaroop VS, Gostout CJ. Endoscopic treatment of chronic radiation proctopathy. J Clin Gastroenterol 1998;27:36-40.  Back to cited text no. 1
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;32:1289-300.  Back to cited text no. 2
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 Database Syst Rev 2002;1:CD003455.  Back to cited text no. 3
Coia LR, Myerson RJ, Tepper JE. Late effects of radiation therapy on the gastrointestinal tract. Int J Radiat Oncol Biol Phys 1995;31:1213-36.  Back to cited text no. 4
Haas EM, Bailey HR, Faragher I. Application of 10 percent formalin for the treatment of radiation-induced hemorrhagic proctitis. Dis Colon Rectum 2007;50:213-7.  Back to cited text no. 5
Do NL, Nagle D, Poylin VY. Radiation proctitis: Current strategies in management. Gastroenterol Res Pract 2011;2011:917941.  Back to cited text no. 6
Cotti G, Seid V, Araujo S, Souza AH Jr., Kiss DR, Habr-Gama A, et al. Conservative therapies for hemorrhagic radiation proctitis: A review. Rev Hosp Clin Fac Med Sao Paulo 2003;58:284-92.  Back to cited text no. 7
Willett CG, Ooi CJ, Zietman AL, Menon V, Goldberg S, Sands BE, et al. Acute and late toxicity of patients with inflammatory bowel disease undergoing irradiation for abdominal and pelvic neoplasms. Int J Radiat Oncol Biol Phys 2000;46:995-8.  Back to cited text no. 8
Beard CJ, Propert KJ, Rieker PP, Clark JA, Kaplan I, Kantoff PW, et al. Complications after treatment with external-beam irradiation in early-stage prostate cancer patients: A prospective multiinstitutional outcomes study. J Clin Oncol 1997;15:223-9.  Back to cited text no. 9
Mathai V, Seow-Choen F. Endoluminal formalin therapy for haemorrhagic radiation proctitis. Br J Surg 1995;82:190.  Back to cited text no. 10
Kochhar R, Patel F, Dhar A, Sharma SC, Ayyagari S, Aggarwal R, et al. Radiation-induced proctosigmoiditis. Prospective, randomized, double-blind controlled trial of oral sulfasalazine plus rectal steroids versus rectal sucralfate. Dig Dis Sci 1991;36:103-7.  Back to cited text no. 11
Sharma B, Pandey D, Chauhan V, Gupta D, Mokta J, Thakur SS. Radiation proctitis. JIACM 2005;6:146-51.  Back to cited text no. 12
Samalavicius NE, Dulskas A, Kilius A, Petrulis K, Norkus D, Burneckis A, et al. Treatment of hemorrhagic radiation-induced proctopathy with a 4% formalin application under perianal anesthetic infiltration. World J Gastroenterol 2013;19:4944-9.  Back to cited text no. 13
Biswal BM, Lal P, Rath GK, Shukla NK, Mohanti BK, Deo S, et al. Intrarectal formalin application, an effective treatment for grade III haemorrhagic radiation proctitis. Radiother Oncol 1995;35:212-5.  Back to cited text no. 14
Saclarides TJ, King DG, Franklin JL, Doolas A. Formalin instillation for refractory radiation-induced hemorrhagic proctitis. Report of 16 patients. Dis Colon Rectum 1996;39:196-9.  Back to cited text no. 15
Pironi D, Panarese A, Vendettuoli M, Pontone S, Candioli S, Manigrasso A, et al. Chronic radiation-induced proctitis: The 4% formalin application as non-surgical treatment. Int J Colorectal Dis 2013;28:261-6.  Back to cited text no. 16
Henson C. Chronic radiation proctitis: Issues surrounding delayed bowel dysfunction post-pelvic radiotherapy and an update on medical treatment. Therap Adv Gastroenterol 2010;3:359-65.  Back to cited text no. 17
Vanneste BG, Van De Voorde L, de Ridder RJ, Van Limbergen EJ, Lambin P, van Lin EN, et al. Chronic radiation proctitis: Tricks to prevent and treat. Int J Colorectal Dis 2015;30:1293-303.  Back to cited text no. 18


  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3]


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