There are no standardized treatment measures for radiation proctitis, and various treatment methods such as drug therapy, retention enema, formaldehyde cautery, argon ion coagulation, hyperbaric oxygen chamber therapy, and surgical treatment have shown their effectiveness to some extent, but their results are mostly small single-center non-double-blind studies, and there are not many treatment means supported by high-quality research evidence.
1.Pharmacological treatment The main therapeutic drugs for blood in stool are enemas, which mainly serve to reduce inflammatory edema, rebuild the mucosal barrier, and stimulate epidermal cell regeneration. The combination can include steroidal enemas, non-steroidal anti-inflammatory agents, short-chain fatty acids, mucosal protective agents, acidifiers and Chinese herbs, etc., which can be supplemented with gentamicin, metronidazole, lidocaine, etc. An RCT has been conducted to show that hydrocortisone enemas are superior to betamethasone enemas in improving clinical symptoms, although there is no significant difference in their endoscopic changes; aluminum thioglycollate and metronidazole have been considered to have definite benefits in improving the symptoms of radiation proctitis and increasing the efficiency of treatment; a randomized double-blind placebo-controlled RCT in 2005 confirmed that oral vitamin A significantly improved rectal symptoms in patients with radiation enteritis A 2005 randomized, placebo-controlled RCT demonstrated that oral vitamin A significantly improved rectal symptoms in patients with radiation enteritis, possibly due to its mucosal healing effects. Some newer drugs are still under investigation, such as WF10, a new chlorite drug for the treatment of radiation proctitis, which improves the healing of the diseased bowel by blocking the inflammatory response of the submucosal vessels. Therapeutic drugs against diarrhea currently except opioid blockers are considered to have a clear role in the treatment of diarrhea, other drugs such as antibiotics, anti-cholestatic amines, anticholinergics and other research mostly stay in small single-center studies.
2, formaldehyde cautery In 1976, Shrom et al. first used formaldehyde cautery in the treatment of radiation cystitis. Based on the successful experience of formaldehyde cautery in radiation cystitis, Rubinstein first used it in the treatment of radiation proctitis in 1986. Formaldehyde acts superficially by causing a protein coagulation mechanism to produce a thrombus within the neovascularization of the mucosal layer thereby providing a hemostatic effect. Local application of formaldehyde is more effective in the treatment of persistent radiation proctitis bleeding, and it has the advantages of being inexpensive, practical, and can be repeatedly treated if the effect is unsatisfactory. However, formaldehyde is also a fixative, highly irritating and may cause acute colitis, fecal incontinence, rectal stricture and more serious anal pain if not properly applied. In the case of low-level radiation proctitis, low-concentration (4%) formaldehyde can be applied locally to the wound for a few tens of seconds to 5 minutes under direct vision after dilation until the wound is white or the bleeding stops, and in the case of higher positions, local spray coagulation can be applied under sigmoidoscopy or colonoscopy, but it must be performed by experienced personnel to prevent complications. showed an efficiency of 55% to 100%, but 7% of patients developed serious complications. In a study of 100 patients, Haas.E et al. showed a 93% efficiency rate and a 1% rate of serious adverse effects in a study in which the wound was covered directly with a dressing soaked in 10% formaldehyde under direct vision. Local formaldehyde cautery hemostasis is effective and can be used as first-line treatment for patients with intractable bleeding, but more RCT studies are needed to derive the optimal dose of formaldehyde and details of local application.
3.Endoscopic treatment Endoscopic treatment includes three methods: laser therapy (Ng:YAG, KTP), argon ion coagulation therapy (APC) and formaldehyde coagulation therapy. Early laser treatment is neodymium-doped yttrium aluminum garnet laser (Ng:YAG Laser), Ng:YAG laser treatment because of its treatment depth is not easy to control has been replaced by potassium titanium phosphate laser treatment (KTP Laser). Argon ion coagulation therapy has gradually shown its advantages in CRP treatment in recent years, it is the use of single electrode technology, the argon ion through the current non-contact action on the surface of the lesion, its depth does not exceed 3mm, not easy to perforate, and argon ion beam can be automatically directed to the surface of the tissue to be treated, the lesion for all-round treatment. The efficiency is about 83%~100%, the average number of treatments is 1~4 times, and the side effects are less. The effectiveness of endoscopic formaldehyde treatment for CRP is described above. There are few comparative studies on KTP Laser, APC, and formaldehyde, and most believe that the three are comparable in terms of efficiency and safety, but some studies have concluded that APC is the best means of endoscopic treatment of CRP. For example, Alfadhli [13] et al. concluded in a retrospective analysis of 22 patients treated with APC or formaldehyde that APC was superior to formaldehyde in terms of efficiency (79% vs 27%), number of treatments (1.78 vs 1.81), and adverse effects (2 cases vs 9 cases).
Hyperbaric oxygen chambers (HBO) can improve tissue ischemia, hypoxia and microcirculatory failure due to vascular endothelial injury in radiation proctitis, increase blood oxygen partial pressure and blood oxygen content, reduce tissue damage, accelerate ulcer healing and promote tissue repair. Two RCT studies (Clarke 2004, Bennett 2005) have demonstrated that HBO can significantly improve mucosal healing in CRE. The disadvantage of this treatment is that it requires special equipment and is expensive.
The indications for surgery include: severe complications such as intestinal obstruction, intestinal perforation, intestinal fistula, intestinal hemorrhage, or intractable symptoms that have failed repeated conservative treatment. Surgical treatment of intestinal injury in CRP is a difficult problem, and the timing of surgery and surgical modality should be selected with great care. The principle of surgery should be to address clinical symptoms as the primary goal, select a reasonable surgical method, minimize surgical morbidity and mortality and complications, and improve prognosis and long-term quality of life.
The surgical treatment includes two broad approaches, namely intestinal resection anastomosis phase I anastomosis and conservative surgery such as short circuit and stoma. The main disadvantage is the occurrence of anastomotic fistula, but the occurrence of anastomotic fistula is closely related to the choice of its location, and colostomy should be necessary if the intraoperative anastomosis is unsatisfactory or if there is stenosis in the distal intestine. If the general condition of the patient is poor or if extensive intraoperative adhesions and “frozen pelvis” are seen, conservative surgery should be performed, which has the advantage of simple operation and few surgical complications, but the disadvantage is that the risk of bleeding, perforation, infection and blind collaterals syndrome exists in the open diseased intestine, which often requires secondary surgery or emergency surgery, and the risk of surgery at this time will Regimbeau et al. conducted a multicenter study of 109 patients with chronic radiation enterocolitis who underwent surgery with a mean follow-up of 40 months and found that the rate of secondary surgery was higher in the conservative surgery group than in the bowel resection group (50% vs. 34%), and the rate of death was significantly higher in the emergency surgery than in the plain surgery (11% vs. 1%).
In addition to these surgical procedures, fistula repair and skin or muscle flap grafting may be considered for radiation enterocutaneous fistulas such as rectovaginal fistulas, rectocystic fistulas, and complex fistulas. McNevin et al. showed a 94% healing rate in 16 patients with radiation enterocutaneous fistulas treated with a bulbocavernosus muscle graft. The goal of surgical treatment of radiation enterocutaneous fistula is to restore the integrity and continuity of the intestinal tract, restore the transoral diet, and improve the quality of life.
6. Other treatments Defecation training, biofeedback and appropriate antidiarrheal medication are useful for patients with anal incontinence, but there are few studies and a lack of clear and effective treatments. Retrospective analysis shows that topical application of phenylephrine can have an efficiency of about 75%, which is one of the means that is still supported by evidence.
Micheli reported in JCO 2003 a case of recalcitrant anal pain after radiotherapy, which was treated with botulinum toxoid A 100U for the whole circumference of the anal sphincter after various methods had failed. It may be related to the inhibition of presynaptic acetylcholine release from the neuromuscular junction.