Hyperbaric Treatment of Radiation Proctitis

Etiology

Radiation proctitis (damage to the lower parts of the colon) is soft tissue radionecrosis and a delayed effect of therapeutic radiation.  As such, it is thought to be a sequela of radiation-induced, progressive, obliterative endarteritis resulting in a lack of small blood vessels in the affected tissue with chronic mucosal ischemia, submucosal fibrosis, progressive epithelial atrophy, and new vessel formation (telangiectasia). It occurs 6 months to years after exposure to the radiation.[1]

Epidemiology

There is an incidence of 1% to 5% of developing chronic radiation proctitis after radiation doses greater than 5000 cGy for pelvic cancer.  Some report an incidence as high as 10%.

Pathophysiology

The late radiation changes cause friable inflamed mucosa (mucositis).  This can lead to ulcerations and bleeding that sometimes require recurrent transfusions. Strictures and fibrosis can occur leading to intestinal obstruction and fistula formation which often have significant morbidity.

Histopathology

Histopathological findings include arteriolar endarteritis and connective tissue fibrosis; whereas, gross findings include mucosal friability, pallor, telangiectasias, strictures, fistulas, and ulcerations.

History and Physical

Signs and symptoms include hematochezia, mucus discharge, diarrhea, tenesmus, and fecal incontinence.[2]

History should include radiation therapy report as radiation proctitis is unusual with doses less than 5000 cGy.

A physical examination may reveal perirectal fistula, anal ulceration, and a fibrotic rectum with mucus and blood.

Evaluation

The physician must keep the history of the initial disease in mind to assess for recurrence of cancer.

1. Digital rectal examination
2. Proctoscopic examination
3. Colonoscopy is needed to fully delineate the extent of inflammation and ulceration and exclude malignancy

Biopsies do not contribute to the diagnosis and should be avoided because of the risk of severe rectal wall damage that may lead to necrosis and fistulas.

Treatment / Management

The American Society of Colon and Rectal Surgeons' clinical practice guidelines for the treatment of chronic radiation proctitis[2] recommend hyperbaric oxygen therapy as an effective treatment modality to reduce bleeding in patients with radiation proctitis. The society strongly recommends the therapy based on moderate-quality evidence.  It is believed hyperbaric oxygen therapy improves tissue oxygenation long-term through angiogenic effects. It also promotes re-epithelialization and stimulates collagen formation. Typically, patients require 30 to 40 treatments for successful resolution of radiation proctitis. The radiation is well tolerated with good outcomes in more than 85% of patients. It alleviates symptoms in 89% for patients with radiation proctitis and sustains the improvement for at least 6 to 12 months after treatment.[3](A1)

Hyperbaric oxygen can be adjunctive to other therapies that are used for this condition, for example, formalin application, sucralfate retention enemas, 5-aminosalicylic acid derivatives, probiotics, antioxidants, antibiotics, and endoscopic argon beam plasma. Sucralfate enemas are very efficacious, inexpensive, and well-tolerated. They may be the best first choice for treatment. Hyperbaric oxygen therapy can be used concurrently or in the case of failure of other treatments.[4]

Bowel surgeries have a high complication rate, more than 70% in some reports.[5] Hyperbaric oxygen treatments before surgical intervention greatly reduce the complication rate and increase the chance of successful resolution.(B2)

Differential Diagnosis

It is important for clinicians to eliminate the diagnosis of cancer recurrence. Symptoms alone do not adequately differentiate between radiation proctitis and a more significant pathology. In one study of 171 patients with rectal bleeding after radiation therapy, 141 had radiation proctitis. However, researchers made 95 additional diagnoses, including 8 cancer diagnoses and 9 cases of high-risk adenomas.[6]

Radiation Oncology

Acute proctitis occurs within the first few months of radiation treatment in 10% to 15% of patients. It is self-limited, lasting for only a few months. It is an inflammatory process of rectal mucosa with a loss of microvilli, edema, and ulceration. Symptoms include abdominal pain, tenesmus, diarrhea, incontinence, and urgency.[7]

Chronic proctitis, often with bleeding, develops months to years after radiation treatment and is often progressive. Severe acute proctitis is a risk factor for chronic proctitis development as are diabetes mellitus, inflammatory bowel disease, connective tissue disease, hypertension, smoking, peripheral vascular disease, and chemotherapy.

Pertinent Studies and Ongoing Trials

In the future, hyperbaric oxygen may be a preventative strategy for radiation proctitis and other soft tissue radiation effects.  Radiation induces a significant elevation of oxidative stress, antioxidants, and pro-fibrotic factors that are completely reversed and normalized by hyperbaric oxygen in animal studies.[8] The therapy may prevent radiation-induced changes by affecting oxidative stress and inflammatory cascades induced by radiation.

Treatment Planning

Patients generally require 30 to 60 hyperbaric oxygen treatments, depending on the severity of their condition. There are daily, 90-minute sessions at hyperbaric pressure. Treatment pressures vary among providers, ranging from 1.5 atmospheres absolute (ATA) to 2.5 ATA.  There is a paucity of research regarding optimal treatment pressure and protocol.

Toxicity and Adverse Effect Management

Patients who cannot equalize their ears may elect to undergo bilateral venting tube myringotomies to prevent significant otic barotrauma.

Prognosis

A randomized, controlled, double-blind, crossover trial showed marked improvement in refractory radiation proctitis with hyperbaric oxygen over control.[3] Complete resolution of bleeding and urgency have been reported in about 50% in retrospective studies. An Australian study reported success rates of 95% with hyperbaric oxygen therapy.[9]

Complications

Hyperbaric oxygen therapy is a relatively low-risk therapy. Otic barotrauma is common but usually not severe. Infrequent complications include oxygen toxicity seizures, transient myopia, and rare cataract formation. Patients with severe structural lung disease or poor left ventricular function are susceptible to more serious complications such as pulmonary barotrauma and acute pulmonary edema.

Contraindications to hyperbaric therapy include recent use of doxorubicin or bleomycin, claustrophobia, epilepsy, severe emphysema particularly with blebs, and certain implanted devices.