Intestinal Radiation Injury Treatment & Management

Updated: Feb 12, 2018
  • Author: Rajeev Vasudeva, MD; Chief Editor: BS Anand, MD  more...
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Treatment

Medical Care

The treatment of acute injury varies depending on the symptoms, and the treatment of chronic injury varies depending on the location of injury.

For symptom control, consider antidiarrheals, bile-sequestering agents, antiemetics, 5-aminosalicylic acid (5-ASA) moieties, and sucralfate. Simple iron supplementation may suffice in some individuals with low-grade bleeding leading to mild anemia.

Consider topical steroids and sucralfate enemas if symptoms are related to rectal involvement. 5-ASA enemas have not been found to be very helpful.

Consider formalin instillation of the rectum and therapeutic endoscopic interventions (eg, ablation with argon, Nd:YAG laser, bipolar circumactive probe [BICAP], argon plasma coagulator). A retrospective study compared formalin instillation with Argon Plasma Coagulator (APC) in a small number of patients and suggested that APC was more effective and safer than formalin in controlling hematochezia and resulted in higher hemoglobin levels. [10]

Hyperbaric oxygen (HBO) therapy may be considered in intractable radiation proctitis before surgical intervention.

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Surgical Care

Surgical intervention usually is required as a last resort or in the case of complications (eg, perforation, obstruction, abscess drainage, fistulae, local wound infections). The surgical approach should be as conservative as possible.

Abdominopelvic operations are best avoided in patients who have received high-dose radiation to the pelvis. Resection of the rectum carries an operative morbidity rate of 12-65% and a mortality rate of 0-13%.

Resection of the diseased bowel can be difficult because identifying the affected loops at laparotomy may be problematic. Doppler viewing of the bowel and intraoperative frozen sections have not been helpful.

An intestinal bypass procedure may be necessary depending on the surgical findings and technical difficulties. Although resection has been shown to cause a higher incidence of leakage and mortality than bypass, the diseased bowel left behind also can cause more bleeding and can result in perforation and fistulization.

Several techniques have been described for resection with primary anastomosis, or secondary anastomosis with diversion colostomy or ileostomy.

When at least one end of a primary anastomosis is healthy bowel, reports exist that leakage is reduced significantly.

Dilation of strictures may be required. Perforation risk is significant if the strictures are long.

Rectovaginal fistulae may close spontaneously or after diversion colostomy. Other fistulae usually require surgical repair.

Presacral sympathectomy has been used for amelioration of severe pain.

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Consultations

A team approach is extremely important to treat these patients. The team may include a radiation oncologist, a medical oncologist, a gastroenterologist, a nutritionist, and, possibly, a surgeon.

The services of a pain specialist may be necessary if the pain is intractable and severe.

Also, the services of a physician experienced with hyperbaric oxygen (HBO) therapy may be necessary if this modality is considered in intractable proctitis.

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Diet

Although no restriction on activity is necessary, on the basis of animal studies, a low-fat diet is recommended, with the intention of reducing pancreatic and biliary secretions to decrease radiation damage. A low-fat, low-residue, and lactose-free diet has been tried with some suggested success. Elimination of insoluble fiber from the diet with the substitution of soluble fiber has been tried.

Findings from animal studies suggest that glutamine-supplemented diets (eg, polymeric, elemental) may be protective against radiation injury.

Consider an elemental diet or the use of total parenteral nutrition as the clinical situation demands. A recent Italian retrospective study in patients with mechanical bowel obstruction due to chronic radiation enteritis showed that initial treatment with bowel rest and home parenteral nutrition was superior to initial surgical intervention in long-term survival and nutrition autonomy.

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Prevention

Note the following:

  • Prevention is the single most important element in dealing with intestinal radiation injury.

  • Although pretreatment calculation of the dose is important, sensitive probes have been replaced by computer calculations. Three-dimensional treatment-planning techniques have been employed and have been shown to be more accurate and safer.

  • A small decrease in radiation (as small as 10%) with an increase in the duration may reduce adverse effects significantly without affecting the total radiation dose.

  • Pretreatment barium contrast studies to determine how much of the small intestine is in the pelvis might be a guide in custom shielding.

  • Filling the urinary bladder may push the small bowel away from the pelvis.

  • Body positioning in the prone position, decubitus, or the Trendelenburg position may be helpful. A special table with a central cavity, which allows the bowel loops to drop away from the target tissue, has been described.

Investigational pharmacologic therapy

A number of promising innovative pharmacologic therapies are being studied. [11, 12, 13]  Unfortunately, most of the data are from animal studies, and trials in humans are lacking. These agents include antioxidants in the form of vitamin E and vitamin E-like compounds, as well as the lazaroids (ie, 21-amino steroids) and, more recently, octreotide.

Although nonsteroidal anti-inflammatory drugs have shown some promise in animal studies, the results with a prostaglandin analogue, misoprostol, have been less than satisfactory.

Other emerging therapies include intravenous and intra-arterial vasopressin, epidermal growth factor, growth hormone, and nitric oxide (NO) inhibitors.

Sucralfate therapy in doses varying from 1 g every 4-6 hours during treatment and for another 3-4 weeks thereafter has been shown to be effective during pelvic irradiation. However, a more recent study showed that oral sucralfate was not effective in preventing late rectal injury in patients with prostate cancer.

The US Food and Drug Administration (FDA) approved the use of IV amifostine (Ethyol) as a radioprotectant agent. Administered as a daily dose, amifostine is to be used in the prevention of radiation-induced xerostomia in the postoperative setting. Its efficacy in the prevention of radiation intestinal injuries has yet to be established. Concern about tumor protection appears to be unwarranted. Adverse effects, such as nausea and hypotension, the need for daily injections, and cost concerns may limit its wide acceptance.

Animal studies

A murine study by Qiu et al described a novel molecular mechanism of growth factors in suppressing p53 upregulated modulator of apoptosis (PUMA) in acute radiation-induced gastrointestinal damage and gastrointestinal syndrome through the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/p53 axis in the intestinal stem cells. [14]

In a different murine study, Cheng et al reported novel functions for receptor for activated C kinase 1 (Rack1) in regulating crypt cell proliferation and regeneration, promoting differentiation and apoptosis, and repressing development of neoplasia. [15]

In a murine and rat study, Valuckaite et al investigated the ability of a high-molecular-weight polyethylene glycol-based copolymer, PEG 15-20, to protect the intestine against the early and late effects of radiation as well as assessed its mechanism of action in cultured rat intestinal epithelia. [16]

PEG 15-20 was able to prevent radiation-induced intestinal injury in the rats, as well as prevent apoptosis and lethal sepsis attributable to Pseudomonas aeruginosa in mice. In addition, the cultured intestinal epithelial cells were protected from apoptosis and microbial adherence and possible invasion. [6]  The investigators noted that PEG 15-20 exerted a protective effect by preventing coalescence of lipid rafts by binding them. [16]

There have been some promising reports in animal studies that probiotics may be helpful in preventing radiation induced intestinal damage. [16, 17, 18, 19]  It remains to be seen whether this intervention turns out to be a preventative or therapeutic tool in human subjects.

In a more recent murine study, the antineoplastic small molecular agent BCN057 induced intestinal stem cell repair and mitigated radiation-induced intestinal injury. [20]

Another murine study indicated that the combination of podophyllotoxin and rutin (G-003M) improved survival of mice after lethal radiation intestinal injury by preventing oxidative stress-mediated cell death and promoting structural and functional regeneration in intestinal tissue. [21]

Prophylactic surgical intervention

As noted above, the most important aspect of intestinal radiation injury is prevention; therefore, a number of innovative prophylactic surgical therapies have been proposed, and include the following:

  • Biodegradable mesh slings

  • Sodium chloride–filled tissue expanders

  • Inflatable prosthesis

  • Abdominopelvic omentopexy

  • Suturing the bladder to the sacrum

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