Radiation proctitis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Rekha, M.D., Mahshid Mir, M.D. [2]

Radiation proctitis is inflammation and damage to the lower parts of the colon after exposure to x-rays or other ionizing radiation as a part of radiation therapy. Radiation proctitis most commonly occurs after treatment for cancers such as cervical cancer, prostate cancer, and colon cancer. Radiation proctitis involves the lower intestine, primarily the sigmoid colon and the rectum.The rectum is at risk of injury during pelvic irradiation because of its fixed position and close proximity to target organs. In 1897, Walsh was the first to discover the association between X-ray (radiation) and the damaging effect on GIT tract in a person working with the radiation energy.He further reported the improvement in the symptoms if exposure being shielded by the lead. In 1942, the early and late intestinal effect of radiotherapy was first described by Warren and Friedman. Based on the duration of symptoms, Radiation proctitis may be classified as either acute or chronic. The exact pathogenesis of radiation proctitis is not fully understood however it is thought that acute radiation proctitis is due to direct damage of the lining (epithelium) of the colon.Chronic radiation proctitis occurs in part because of damage to the blood vessels which supply the colon and results in full-thickness ischemia and fibrotic changes and ultimately the colon is therefore deprived of oxygen and necessary nutrients. Radiation proctitis must be differentiated from infectious colitis, inflammatory bowel disease, ischemic colitis, medication-associated colitis, chemical colitis, and allergic colitis. The reported incidence of any transient acute radiation proctitis is thought to range from 50% to 100%. The incidence of chronic radiation proctitis is estimated to be 2000-20,000 in every 100,000 radiations. Common complications of radiation proctitis include intestinal obstruction due to stricture, fecal incontinence due to overflow and fistula formation due to concomitant injury to nearby organs. The laboratory findings in a patient with acute radiation proctitis can be within reference range however, in case of chronic injury anemia, elevated white blood cell, deranged LFTs and electrolyte abnormalities can be seen.

X- Ray was first discovered by Wilhelm Roentgen, in 1895. In 1897, Walsh was the first to discover the association between X-ray (radiation) and the damaging effect on GIT tract in a person working with the radiation energy.He further reported the improvement in the symptoms if exposure being shielded by the lead. In 1942, the early and late intestinal effect of radiotherapy was first described by Warren and Friedman.

Based on the duration of symptoms, Radiation proctitis may be classified as either acute or chronic.

The exact pathogenesis of radiation proctitis is not fully understood however it is thought that acute radiation proctitis is due to direct damage of the lining (epithelium) of the colon.Chronic radiation proctitis occurs in part because of damage to the blood vessels which supply the colon and results in full-thickness ischemia and fibrotic changes and ultimately the colon is therefore deprived of oxygen and necessary nutrients.

Common causes in the development of Radiation proctitis include include dose of radiation, area of the radiation and mode of delivery of the radiation.

Radiation proctitis must be differentiated from infectious colitis, inflammatory bowel disease, ischemic colitis, medication-associated colitis, chemical colitis, and allergic colitis.

The reported incidence of any transient acute radiation proctitis is thought to range from 50% to 100%. The incidence of chronic radiation proctitis is estimated to be 2000-20,000 in every 100,000 radiations.

Common risk factors in the development of Radiation proctitis include include dose of radiation, area of the radiation and mode of delivery of the radiation.

There is insufficient evidence to recommend routine screening for radiation proctitis however recent studies shows that the impairment of the rectum’s ability to heal may predispose other organs, exposed to the radiation, at high risk of malignant transformation so It has been suggested that patients exposed to higher doses of radiation may need to be more closely screened for other malignancies but further studies need to be conducted before definitive recommendations can be made. The risk of second cancer after irradiation, although probably small, needs nevertheless to be carefully monitored.

The symptoms and extent of radiation proctitis are variable and usually develop insidiously. The symptoms depend on the dose and duration of the radiation and how sensitive the bowel is to radiation.

Common complications of radiation proctitis include intestinal obstruction due to stricture, fecal incontinence due to overflow and fistula formation due to concomitant injury to nearby organs.

The prognosis of radiation colitis varies with the sub-type, severity, duration and responsiveness to treatment.

There is no definitive diagnostic study of choice for radiation proctitis. Diagnosis of radiation proctitis is primarily clinical; it is based on history, physical examination and endoscopic findings.

The most common symptoms of Radiation proctitis include mild diarrhea, tenesmus, fecal urgency and mucus discharge. Less common symptoms of radiation proctitis include abdominal pain,constipation,severe diarrhea and rectal bleeding.

Patients with radiation proctitis may appear pale and dehydrated. Some patients may appear fatigued and in distress, associated with abdominal pain.

The laboratory findings in a patient with acute radiation proctitis can be within reference range however, in case of chronic injury anemia, elevated white blood cell, deranged LFTs and electrolyte abnormalities can be seen.

Barium studies can be done in patients who have obstructive symptoms or those suspected of having fistulas.

Other diagnostic studies such as colonoscopy, tissue biopsy and histological analysis can help with the diagnosis of radiation proctitis.

Acute radiation proctitis is a self limiting condition and treated conservatively however in 20% of cases undergoing external beam radiation will require short interruptions in their treatment to improve symptoms.In case of chronic radiation proctitis treatment usually depends upon the severity and pattern of the symptoms.

Surgery is not the first-line treatment option for patients with radiation proctitis.However it is usually reserved as a last resort for patients with refractory symptoms and complications.

Primary prevention of radiation proctitis can be done by the modifications of radiation techniques and doses or by use of prophylactic adjunct medical and surgical therapies.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Rekha, M.D., Mahshid Mir, M.D. [2]

In 1897, Walsh was the first to discover the association between X-ray (radiation) and the damaging effect on GI tract in a person working with the radiation energy. He further reported the improvement in the symptoms if exposure being shielded by the lead. In 1942, the early and late intestinal effect of radiotherapy was first described by Warren and Friedman.

• X- Ray was first discovered by Wilhelm Roentgen, in 1895.
• In 1897, Walsh was the first to discover the association between X-ray (radiation) and the damaging effect on GI tract in a person working with the radiation energy. He further reported the improvement in the symptoms if exposure being shielded by the lead.
• In 1912, Regaud et al. described the delayed effects on the irradiation in the small intestine of the dogs.^[1]
• In 1917, the first case of the radiation enteritis being reported in a patient being treated for the malignant disease.
• In 1930, factitial proctitis was discovered in group of patient who had undergone the pelvic radiations by Buie.
• The early and late intestinal effect of radiotherapy was first described by Warren and Friedman in 1942.
• In 1976, Goldstein et al. observed clinical improvement of a patient with radiation-induced proctitis who received salicylazo-sulfapyridine in combination with prednisone.^[2]
• In 1977, Pajares et al. also observed a decrease of rectal bleeding after administration of prednisone.
• In 1984, Ben Bouali et al. demonstrated clinical and endoscopic improvement in 4 out of 33 patients treated with daily rectal administration of 5 mg of betamethasone in combination with diphenoxylate
• More recently, Triantafillidis et al. reported 5 patients treated for RP with enemas containing 5mg of betamethasone without any clinical improvement.
• In 1999, Kochhar et al. demonstrated that topical sucralfate produced sustained resolution of symptoms.^[2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Rekha, M.D., Mahshid Mir, M.D. [2]

Based on the duration of symptoms, radiation proctitis may be classified as either acute or chronic.

Based on the duration of symptoms, radiation proctitis may be classified as either acute or chronic in relation to the radiation treatment as well as the presenting symptoms and signs.^[1]

Acute radiaition proctitis usually occurs within six weeks of radiation treatment.It is a self limiting condition that resolves after discontinuation of the treatment and doesn’t increases the risk of the chronic proctitis.It presents with the symptoms of diarrhea, tenesmus, nausea, cramps, urgency and sometimes minor bleeding requiring to interrupt the treatment.^[1]

Symptoms may begin as early as several months after therapy but occasionally not until several years later. These symptoms include diarrhea, rectal bleeding, painful defecation, and intestinal obstruction. Intestinal blockage is a result of narrowing of the rectum which blocks the flow of feces due to stricture and results in symptoms in the form of constipation, rectal pain, urgency, and rarely fecal incontinence due to overflow. Connections fistulae may also develop between the colon and other parts of the body such as the skin or urinary system. Injury to the nearby organs can lead to cystitis, urethral stenosis, small bowel obstruction and small bowel bacterial overgrowth.^[2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Rekha, M.D., Mahshid Mir, M.D. [2]

The exact pathogenesis of radiation proctitis is not fully understood however it is thought that acute radiation proctitis is due to direct damage of the lining (epithelium) of the colon. Chronic radiation proctitis occurs in part because of damage to the blood vessels which supply the colon and results in full-thickness ischemia and fibrotic changes and ultimately the colon is therefore deprived of oxygen and necessary nutrients.

• Acute radiation proctitis is due to direct damage of the lining (epithelium) of the colon. ^[1]
• Chronic radiation proctitis occurs in part because of damage to the blood vessels which supply the colon and results in full-thickness ischemia and fibrotic changes and ultimately the colon is therefore deprived of oxygen and necessary nutrients.^[2]

• Ionizing radiation primarily damages DNA leading to the apoptosis of targeted tumor cells, however inadvertently intestinal crypt stem cells in the radiation field get also affected resulting in crypt involution, mucosal injury, and exposure of the underlying lamina propria to luminal bacteria and activation of acute inflammatory response.
• Secondary to significant production of enzymes and reactive oxygen metabolites by these inflammatory cells, further degradation of the extracellular matrix and injury to mucosal and submucosal tissue ensures, causing further damage to the bowel wall.
• After the cessation of radiation exposure, intestinal crypt cells regenerate and the mucosal surface is repopulated with epithelium with the resolution of acute inflammatory response.
• However, progressive exposure causes ulceration followed by progressive fibrosis and the development of chronic inflammatory changes associated with chronic symptoms.
• Endothelial damage causes arterial sclerosis with obliterative endarteritis of small vessels, leading to chronic ischemia and associated fibrosis.
• These changes can lead to ulcers, bleeding, stenosis, strictures, fistulas, and bleeding.

On gross pathology, rectal mucosa in acute radiation proctitis appears edematous, erythematous (beefy red), and may have ulceration or sloughing however the intestines are pale, non compliant with telangiectasias, and may have strictures, ulcerations, fistulas, or heavy bleeding in case of chronic radiation proctitis.^[3]

On microscopic histopathological analysis, there is a loss or distortion of the microvillus architecture with hyperemia, edema, and ulceration in acute radiation proctitis. However progressive mucosal atrophy, chronic mucosal ischemia, focal distortion and destruction of small arteries and arterioles with intimal fibrosis and new vessel formation can be seen in case of chronic radiation proctitis.^[3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Rekha, M.D., Mahshid Mir, M.D. [2]

Common causes in the development of radiation proctitis include include high dose of radiation, area of the radiation and mode of delivery of the radiation.

Common causes in the development of radiation proctitis include:^[1][2]

• Dose of the radiation: <45 Gy are associated with few long-term radiation side effects. In contrast, doses between 45 and 70 Gy cause more complications, and doses above 70 Gy cause significant and longstanding injury to the surrounding area.
• Area of the radiation.^[3]
• Mode of the delivery of the radiation: External beam radiation, typically administered by a linear accelerator, results in significantly greater exposure to surrounding organs as compared with brachytherapy, where radiation is administered via radioactive implants. Newer modalities of external beam radiation delivery, including three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and the use of heavy particles including protons and neutrons, may be associated with a reduced risk of radiation toxicity.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Rekha, M.D., Mahshid Mir, M.D. [2]

Radiation proctitis must be differentiated from infectious colitis,inflammatory bowel disease,ischemic colitis,medication-associated colitis,chemical colitis and allergic colitis

The following conditions may present in a similar manner as radiation proctitis, and should be excluded:^[1]

• Infectious colitis,
• Inflammatory bowel disease,
• Ischemic colitis,
• Medication-associated colitis
• Chemical colitis
• Allergic colitis

The table below lists the differential diagnosis of common causes of colitis:

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Rekha, M.D., Mahshid Mir, M.D. [2]

The reported incidence of any transient acute radiation proctitis is thought to range from 50% to 100%. The incidence of chronic radiation proctitis is estimated at 2%–20%

• The exact incidence of the radiation proctitis is not available and largely depends on number of factors such as:

• • The dose of radiation
  • Area of exposure
  • Method of delivery
  • The use of cytoprotective agents
  • Dose fraction regimens
  • The interval between sessions

• The reported incidence of any transient acute radiation proctitis is thought to range from 50% to 100%.^[1]
• The incidence of chronic radiation proctitis is estimated to be 2000-20,000 in every 100,000 people.^[2]
• The incidence rate of radiation proctitis in patients treated with the external beam radiation therapy is estimated to range from 2000-39,000 in every 100,000 patients depending upon the severity and grade of proctitis.^[3]
• The incidence rate of radiation proctitis in patients treated with brachy-therapy is 8000-13,000 in every 100,000 patients when used alone and up to 21,000 in every 100,000 ptients in combination with other modalities.^[4]
• Smith et al. reported a 20,000 in every 100,000 patients incidence of RP with a radiation dose up to 7.500 Cgy and a 60,000 in every 100,000 patients incidence of RP with doses greater than 7.500 Cgy.^[5]
• Furthermore, it is unclear whether the incidence of radiation proctitis is increasing or decreasing. Although newer radiotherapy techniques may reduce the damage to surrounding tissues, potentially reducing the incidence of proctitis, it is possible that the higher doses used may have the opposite effect. Also, as the number of cancer patients receiving radiation to the pelvic area increases, the incidence of radiation proctitis may also increase.

• The prevalence of radiation proctitis is more among older age group (over 60 years) patients. This may be a reflection of the increase frequency of predisposing malignancy requiring radiotherapy in this age group.However, younger age group seems more susceptible to the risk of radiation injury.

• There is no racial predilection to radiation proctitis.

• Radiation proctitis affects men and women equally.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Rekha, M.D., Mahshid Mir, M.D. [2]

Common risk factors in the development of radiation proctitis include include presence of inflammatory bowel disease, concurrent treatment, immunosuppression, other comorbidities and history of previous surgery.

• Common risk factors in the development of radiation proctitis are the diseases that may increases the susceptibility of mucosal injury by radiation are:^[1]
  • HIV^[2]
  • Immunosuppresion^[3]
  • Inflammatory bowel disease
  • History of smoking
  • Diabetes Mellitus
  • Hypertension
  • History of atherosclerosis
  • Younger age
  • Concurrent treatment
  • Previous abdominal surgery
  • Malnutrition
  • Tumour stage
  • Genotypic susceptibility to radiation toxicity

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Rekha, M.D., Mahshid Mir, M.D. [2]

There is insufficient evidence to recommend routine screening for radiation proctitis. However recent studies shows that the impairment of the rectum’s ability to heal may predispose other organs, exposed to the radiation, at high risk of malignant transformation so it has been suggested that patients exposed to higher doses of radiation may need to be more closely screened for other malignancies but further studies need to be conducted before definitive recommendations can be made. The risk of second cancer after irradiation, although probably small, needs nevertheless to be carefully monitored.

• There is insufficient evidence to recommend routine screening for radiation proctitis. However recent studies shows that the impairment of the rectum’s ability to heal may predispose other organs, exposed to the radiation, at high risk of malignant transformation so it has been suggested that patients exposed to radiation may need to be more closely screened for other malignancies but further studies need to be conducted before definitive recommendations can be made.^[1]The risk of second cancer after irradiation, although probably small, needs nevertheless to be carefully monitored.^[2]

• The latency period between radiation exposure and development of a radiation- induced cancer is at least 5 years and persist for >40 years after irradiation. For this reason it is important for anyone who has received pelvic radiation to have long-term surveillance with either a colonoscopy or a flexible sigmoidoscopy starting 5 years after completion of radiation therapy.^[2][3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Rekha, M.D., Mahshid Mir, M.D. [2]

The symptoms and extent of radiation proctitis are variable and usually develop insidiously. The symptoms depend on the dose and duration of the radiation and how sensitive the bowel is to radiation. Common complications of radiation proctitis include intestinal obstruction due to stricture, fecal incontinence due to overflow and fistula formation due to concomitant injury to nearby organs. The prognosis of radiation colitis varies with the sub-type, severity, duration and responsiveness to treatment.

• The symptoms and extent of radiation proctitis are variable and usually develop insidiously. The symptoms depend on the dose and duration of the radiation and how sensitive the bowel is to radiation.^[1]
• In acute radiation proctitis symptoms usually start shortly after commencement of radiation therapy and progress reaching a peak within 6 weeks.In most cases, the symptoms of acute radiation colitis are self-limiting however up to 20 percent of patients with acute radiation proctitis will have symptoms that are severe enough to require an interruption in radiation treatment.
• The chronic radiation proctitis has delayed onset and symptoms often become noticeable months to years after the completion of radiotherapy. The symptoms may occasionally follow acute radiation colitis. However, previous acute radiation colitis does not increase the risk of a patient developing chronic radiation colitis. Also, absence of acute radiation colitis, does not prevent chronic radiation colitis from occurring. Treatment is required for chronic radiation colitis because resolution of the symptoms is uncommon without intervention.^[2]

Common complications of chronic radiation proctitis include:

• Anemia
• Intestinal obstruction due to stricture
• Fistula
• Fecal incontinence due to overflow
• Malabsorption
• Failure to thrive
• Sepsis, due to loss of the mucosal protective barrier
• Concomitant injury to the genitourinary tract or small bowel may lead to intestinal obstruction, small intestinal bacterial overgrowth, urethral stenosis, and cystitis.

• Risk of development of the secondary malignancy

The prognosis of radiation colitis varies with the sub-type, severity, duration and responsiveness to treatment.

• Acute radiation colitis is usually self-limiting, with resolution of symptoms few weeks after cessation of radiotherapy.
• Chronic radiation colitis is progressive and difficult to manage. The patients may develop secondary radiation-associated malignancy which has a poor prognosis due to late diagnosis.

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