Edited by: Rabindra Watson, Cedars Sinai Medical Center, United States
Reviewed by: Darrick Li, Yale University, United States
Gianluca Ferini, Rem Radiotherapy, Italy
†These authors have contributed equally to this work
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Radiation proctitis is a common complication that occurs as a result of radiation therapy used to treat pelvic malignancies. The most common and bothersome symptom resulting from radiation proctitis is rectal bleeding, which can be persistent or recurrent. This study aimed to review our experience and evaluate the efficacy and safety of transcolonoscopic spraying of formalin solution in patients with hemorrhagic radiation proctitis.
A total of 37 patients with hemorrhagic radiation proctitis, aged between 48 and 79 years (mean age 62.56 ± 8.48 years), were divided into three cohorts based on the severity of radiation injury. Under direct endoscopic vision, a 4% formalin solution was applied directly to the rectal hemorrhagic mucosa. The patients were followed for a period of over 6 months after receiving treatment, during which the therapeutic effectiveness and occurrence of complications were observed.
The study resulted in an overall response rate of 89.2% among all patients. The response rates for patients with grades 1–3 were 100, 100, and 66.7%, respectively. Notably, the rate of response among patients with grade 3 radiation injury was significantly lower compared to those with grades 1–2 (
The endoscopic application of formalin solution for the treatment of hemorrhagic radiation proctitis has shown a significant effect, particularly in patients with grades 1–2 radiation injury. The observed effect is superior to that observed in patients with grade 3 radiation injury.
Radiation proctitis is a frequently encountered complication arising from radiation therapy administered for pelvic malignancies. This is primarily attributed to the anatomical positioning and histological attributes of the rectum, particularly in cases of prostatic and cervical cancer (
Formalin therapy was first employed in the treatment of hemorrhagic cystitis in 1969, and subsequently investigated as a potential treatment for radiation-induced hemorrhagic proctitis in 1986. Since then, sporadic reports have appeared in the literature describing more patients and more advanced methodologies for the application of formalin in the rectum. As a sclerosing agent, formalin facilitates the chemical cauterization of mucosal vessels, with various techniques available for its application on rectal lesions. Different methods of formalin therapy have been reported in the literature. The success rate of this method in patients with radiation proctitis, in terms of cessation of bleeding, ranges from 60 to 100% (
Thirty-seven hemorrhagic radiation proctitis in patients admitted to the Civil Aviation Hospital and PLA General Hospital from January 2018 to June 2022 who were treated with transcolonoscopic spraying formalin solution were enrolled in this study.
All patients had clinical evidence of radiation-induced proctitis, which was graded according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale and the Radiation Therapy Oncology Group’s Modified Radiation Toxicity Scale (MRTS), as shown in
Radiation therapy oncology group’s modified rectal toxicity scale (MRTS).
| Grade | Clinical | Symptoms and interventions |
|---|---|---|
| 0 | No impact | No discernable symptoms or intervention |
| 1 | Mild and self-limiting | Minimal, infrequent bleeding or clear mucus discharge, rectal discomfort not requiring analgesics, and loose stools not requiring medications |
| 2 | Managed conservatively, lifestyle (performance status) not affected | Intermittent rectal bleeding not requiring regular use of pads, erythema of rectal lining on proctoscopy, and diarrhea requiring medications |
| 3 | Severe, affects patient lifestyle | Rectal bleeding requiring regular use of pads and minor surgical intervention, rectal pain requiring narcotics, and rectal ulceration |
| 4 | Life-threatening and disabling | Bowel obstruction, fistula formation, bleeding requiring hospitalization, and surgical intervention required |
| 5 | Death | Death directly related to radiation effects |
The participants in this study were required to provide written informed consent before undergoing endoscopy. The study was approved by the Ethical Committee of Civil Aviation General Hospital and met the guidelines of the local responsible governmental agency.
Bowel preparation was performed for all patients prior to the procedure. Subsequently, a routine electronic colonoscopy (CV-290, Olympus Optical Co. Ltd., Tokyo, Japan) was conducted to rule out other hemorrhagic diseases, such as colon polyps, tumors, inflammatory bowel disease, and vascular malformation. All procedures were conducted using an electronic colonoscope in the left lateral decubitus position. The position could be adjusted to either the lateral or prone position if necessary to accurately determine the location of the lesion. Furthermore, 4% formalin solution was directly sprayed on the rectal hemorrhagic mucosa by the colonoscope for 3 min until the bleeding stopped. A saline solution was then used to adequately irrigate the rectum. This procedure could be repeated once or twice if bleeding does not stop, and the total contact time between formalin and the lesion should not exceed 10 min.
All the patients were monitored for blood cell counts, liver and kidney functions, and coagulation function. Patients were reviewed at the outpatient clinic 1, 3, and 6 months after discharge. They were then regularly followed up through telephone and outpatient visits, with rebleeding as the endpoint of the follow-up. Bleeding per rectum, bowel movements, common complications, and systemic toxicities (such as symptoms of respiratory irritation, abnormal liver and renal function, and pancytopenia) were recorded.
Three categories of response were evaluated: a complete response, characterized by the absence of any further episodes of bleeding within a 6-month period; a significant response, indicated by a substantial reduction in bleeding, with no more than 3 episodes occurring within 6 months, and no significant alteration in hemoglobin levels; and a failed response, denoting the persistence of bleeding despite treatment. The response rate was defined as the percentage of patients who achieved a complete response or significant response, out of the total number of patients. The complete response rate is defined as the percentage of patients who achieved a complete response out of the total number of patients.
Data were analyzed using the SPSS 22.0 software package. The measurement data of normal distribution was described by mean ± standard deviation (
A total of 37 participants were included in the study, consisting of 9 men and 28 women. The gender ratio was approximately 1:3.1. The age range of the participants was 48 to 79 years, with a mean age of 62.56 ± 8.48 years. The primary tumors consisted of nine cases of prostate cancer, one case of bladder cancer, five cases of endometrial cancer, one case of vaginal cancer, and 21 cases of cervical cancer. The time period between the completion of radiotherapy and the occurrence of hemorrhagic radiation proctitis in all patients ranged from 9 to 15 months. The duration of hemorrhage prior to treatment ranged from 19 days to 13 months. Among the patients, five were severely anemic, and two required blood transfusions due to severe rectal bleeding. None of the patients underwent endoscopic therapy or received enemas, such as argon plasma coagulation (APC) or sucralfate enema, among others. The patients had no prior history of using antiplatelet and anticoagulant medications before undergoing treatment.
The patients were categorized into three groups based on the severity of radiation-induced injuries. There was no significant difference in the age of the patients and the treatment times. The overall response rate for all patients was 89.2%. There was a significant difference in the effect of formalin on patients with different grades. The response rates observed among patients with grades 1–3 were 100, 100, and 66.7%, respectively. The response rate of patients with grade 3 was significantly lower than that of grades 1–2, as shown in
Comparison of therapeutic effect among different grades.
| Grade 1 | Grade 2 | Grade 3 | ||||
|---|---|---|---|---|---|---|
| 10 | 15 | 12 | ||||
| Age ( |
61.1 ± 7.43 | 62.33 ± 10.77 | 64.08 ± 6.17 | 0.334 | 0.718 | |
| Number of formalin treatments ( |
1.8 ± 0.63 | 1.93 ± 0.7 | 2.5 ± 0.79 | 3.125 | 0.057 | |
| Response rate | 100% | 100% | 66.7% | 9.343 | 0.009 | |
| Complete response | 10 | 13 | 2 | |||
| Significant response | 0 | 2 | 6 | |||
| Failed response | 0 | 0 | 4 | |||
All patients were treated with transcolonoscopic spraying of formalin, and the overall rate of adverse reactions was 16.2%. Mild adverse reactions were reported, most commonly anal pain and tenesmus, but in most cases, these symptoms resolved spontaneously. No significant complications were observed, as indicated in
Comparison of complications among different grades.
| Anal pain | Tenesmus | Fecal incontinence | Anal stenosis | Fistula | Systemic toxicities | ||
|---|---|---|---|---|---|---|---|
| Grade 1 | 10 | 0 | 0 | 0 | 0 | 0 | 0 |
| Grade 2 | 15 | 2 | 1 | 0 | 0 | 0 | 0 |
| Grade 3 | 12 | 3 | 3* | 0 | 0 | 0 | 0 |
*The patient had concurrent anal pain.
HRP is a serious condition that can occur after radiation therapy for pelvic tumors. This condition has a profound impact on the overall quality experienced by affected patients. Digestive endoscopy holds significant importance in the diagnosis of radiation proctitis, and its technique also offers potential for therapeutic intervention. Endoscopic thermal methods are employed with the objective of eradicating all telangiectasia in order to mitigate bleeding. Currently, the use of endoscopic argon plasma coagulation is widespread, as it has been proven to be an effective and popular treatment option for patients with refractory HRP. The technique targets areas of bleeding or telangiectasia, with a success rate ranging from 83 to 100%. However, this procedure can lead to various complications, including rectal ulceration, stricture, bowel perforation, and rectovaginal fistulas (
Formalin, as a type of fixing agent, exhibits a potent protein coagulation effect. This effect leads to the precipitation of cellular proteins and the blockage of telangiectatic lesions and small capillaries. The primary site of action for formalin is the superficial layer, without extending beyond the mucosal layer. A number of studies have shown that patients can achieve a relatively high remission rate by using various concentrations of formaldehyde solution through retention enema, local perfusion, gauze infiltration, etc. (
No severe complications related to the formalin treatment were observed in this study. Only a small number of patients experienced mild symptoms, such as anal pain and tenesmus, which could resolve spontaneously. It has been reported in the literature that the administration of formaldehyde treatment may lead to various adverse effects, including dyschezia, fecal incontinence, anal stenosis, fistula, and rectal cancer (
However, our study has several limitations that may have introduced potential bias. These limitations include the retrospective nature of the study, the small sample size, differences in disease progression, and variations in tumor treatment regimens. Wider prospective randomized controlled trials are required in order to validate the effectiveness and safety of this therapeutic approach.
In conclusion, the application of formalin solution to treat hemorrhagic radiation proctitis under direct vision with the colonoscope has been found to have a significant impact. It offers convenience in terms of application, is cost-effective, and ensures a high level of safety. Especially for patients with grade 1–2 radiation injury, the treatment outcome is better than that for patients with grade 3.
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
The studies involving humans were approved by the Ethical Committee of Civil Aviation General Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.
KH, XZ, and LW: conceptualization and writing — review and editing. KH and LW: methodology and resources. KH, XZ, JY, and JC: formal analysis and investigation. KH: writing — original draft preparation. LW: supervision. All authors reviewed and approved the manuscript.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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