Radiation Enteritis and Proctitis 

Updated: Nov 06, 2019
Author: Neelu Pal, MD; Chief Editor: John Geibel, MD, MSc, DSc, AGAF 

Overview

Practice Essentials

Radiation therapy is a mainstay in the treatment of both primary and recurrent gastrointestinal (GI) and pelvic malignancies.[1, 2]  Combining treatment modalities (surgery, chemotherapy, radiation) allows for the best possible outcome in patients with these malignancies. One of the major and debilitating adverse effects of radiation therapy is the development of radiation enteritis[3] and proctitis. Both radiation enteritis and radiaition proctitis have acute (early) and chronic (late) manifestations.

The direct effects of radiation on the bowel mucosa lead to acute radiation enteritis. Acute radiation enteritis is exceedingly common; virtually every patient has some manifestation of acute radiation-induced injury of the GI tract in the form of abdominal cramping, tenesmus, urgency, bleeding, diarrhea, and incontinence. Typically, these patients are managed symptomatically and supportively. The symptoms of most patients resolve within weeks of radiation therapy cessation.

Chronic radiation enteritis is an indolent but relentlessly progressive disease. Patients may present with symptoms within months or even decades after the injuring radiation therapy. Chronic intestinal radiation injury is a result of transmural bowel damage with associated obliterative endarteritis.

Treatment of these patients is extremely challenging. Initial nonoperative modalities include diet modification, nutritional support, and control of symptoms with medications.[4]  Severe, progressive disease may require surgical intervention, especially for complications, such as fistula formation, obstruction, perforation, and hemorrhage.

Although the benefits of treatment with radiation are well established, damage to the healthy, nonneoplastic tissue may be severe.[5]  The rectum is more commonly injured because of its fixed position in the pelvis. Postoperative adhesions that fix small bowel loops within the pelvis make these loops susceptible to radiation injury. Because radiation is increasingly used to treat pelvic malignancies, the surgical prevention and treatment of the complications of radiation enteritis and proctitis continues to evolve.

Just 2 years after the discovery of x-rays in 1895, Walsh reported the first case of radiation-induced enteritis.[6]  A patient who worked with x-rays had developed abdominal pain and diarrhea, symptoms that resolved with the use of a lead shield. In 1917, the first case was reported of the development of radiation enteritis following the use of radiotherapy to treat malignancy. In 1930, researchers reported the development of factitial proctitis in a group of patients who received pelvic radiation to treat malignant disease.

As the use of radiation therapy and x-rays in medicine increased, the harmful adverse effects were better recognized. Warren and Friedman described both the early and late effects of radiation therapy on the intestine.[7]  Once the risks associated with radiation therapy were recognized, attempts followed to prevent these complications. The development of improved dosimetry techniques, as well as patient selection and positioning during delivery of radiation therapy, were crucial to decrease the harmful effects of radiation on the intestines.

The history of surgical prevention of small-bowel radiation injury is based on the principle of abdominopelvic partitioning. The goal of this procedure is to keep the highly radiation-sensitive small intestine out of the pelvis. In 1979, Freund et al published the first report of a surgical procedure to create abdominopelvic partitioning.[8]  In 1984, Russ et al described the use of an omental pedicle flap. In 1985, DeLuca and Ragins described the creation of an omental envelope to enclose the small bowel.[9]

In 1992, Lechner and Cesnik again described this technique and coined the term abdominopelvic omentopexy.[10]  In 1995, Choi and Lee described the omental hammock technique.[11]  The omental pedicle, based on the left gastroepiploic artery, is sutured circumferentially to the parietal peritoneum at the level of the sacral promontory and the umbilicus. A hammock is created within which the small bowel rests; the hammock prevents the bowel from entering the pelvic cavity.

Patients often lack adequate amounts of omentum or peritoneum to create an abdominopelvic separation. In 1979, Lavery et al reported their use of gauze packs encased in a latex dam to protect the abdominal viscera during high-dose radiotherapy for osteogenic sarcoma of the iliac bone.[12]  In 1983, Sugarbaker described the use of a silicone breast implant to occupy the pelvic cavity.[13]  Hoffman reported the use of saline-filled tissue expanders to occupy the pelvic cavity. In 1984, Devereux et al described, in a group of 60 patients, the use of mesh slings after resection of rectal or gynecologic malignancies.[14]

Historically, the surgical procedures to treat the complications of radiation enteritis have been as minimally invasive as possible, with the goal of relieving symptoms. Patients with fistulas and obstruction underwent bypass, and patients with bleeding associated with radiation proctitis underwent diverting colostomy. In 1976, Swan et al reported that resection for fistulas and obstruction was associated with prohibitive rates of morbidity and mortality. In 1984, Webbes et al and Goligher et al reaffirmed these recommendations. Multiple reports suggest that resection reduces the reoperative rate and improves the 5-year survival rate but leads to a higher rate of postoperative mortality.

Pathophysiology

Histopathologic findings in acute radiation-related intestinal damage include the following characteristics:

  • Transient mucosal atrophy
  • Submucosal edema
  • Inflammation and infiltration of the lamina propria with polymorphonuclear leukocytes and plasma cells

In addition, mitotic arrest, karyorrhexis, and lysis of the crypt and deep epithelial cells are observed. If the submucosal damage is not prominent, the epithelial cells regenerate and the changes regress. Conversely, severe submucosal changes lead to progression of mucosal injury, ulcerations, and erosion of the villi. The histologic findings in the acute phase correlate poorly with clinical symptoms, but amounts of malabsorption vary because of the mucosal damage.

Repopulation of the mucosal cells occurs in the later stage of the acute phase. The severity of the damage to supportive connective tissue limits the degree of reepithelialization. The fibrosis of the underlying connective tissue causes patchy ischemia of the mucosa, which may cause ulceration. Local trauma or infection often precipitates these ulcers.

Histologically, obliterative endarteritis of the small vessels in the intestinal wall characterizes chronic radiation intestinal injury. Associated lymphoid atrophy, lymphatic dilation, and fibrosis of the submucosal tissue are observed. The progressive vascular sclerosis leads to chronic ischemia of the overlying tissue, ultimately resulting in mucosal atrophy. Scar tissue replaces the submucosal tissue, resulting in further decrease in vascularity and contracture of the intestinal wall. Chronic mucosal ulceration may result in fistula formation and hemorrhage.

In the later stages, the colon and rectum are susceptible to the development of radiation-induced carcinomas, which may manifest as ulcers or masses and are often adenocarcinomas.

There is also some evidence supporting a pivotal role for the gut microbiota in the development of radiation-induced bowel injury.[15]

Etiology

Radiation injury to the small and large bowel is due to damage to the lipid layer of the cell membrane, proteins, and cellular DNA. The effects are most marked in tissues containing cells with a high mitotic rate.

Patient-related factors and the method of radiation therapy administration may intensify the effects of radiation-induced intestinal injury. Patient-related risk factors that are associated with an increased risk of radiation-induced enteropathy include the following:

Analysis of multiple risk factors for predictive value demonstrated that multiple laparotomies, hypertension, and thin physique had the highest correlation with the development of radiation enteritis.

Administration of chemotherapy with radiation therapy correlates with an increased incidence of radiation-related intestinal damage. Several studies have documented this effect as well as the recall phenomenon, in which radiation followed with chemotherapy leads to a recurrence of the symptoms of radiation-induced intestinal injury.

The degree of intestinal injury is directly related to the total radiation dose, the fractionation, and the distribution of the dose in tissues peripheral to the target area. Early in the evolution of radiation therapy, large single radiation doses were noted to cause severe or even lethal adverse effects; the same cumulative dose given as small fractions over the course of several days or weeks was better tolerated.

For example, a single 30-Gy dose of radiation to the esophagus is tolerated poorly; however, when the dose is fractionated and spread over 4-6 weeks, even a total dose of 60-70 Gy is tolerated. Similarly, Deore et al demonstrated an increased incidence (8.2-33.3%) of late rectal and rectosigmoid complications as the dose per fraction increased from 2 Gy to 5.4 Gy in patients treated for cancer of the cervix with radiation alone.[16]

Excessive exposure of adjacent normal tissue to radiation also contributes to the development of radiation-induced enteropathy. Current techniques allow for a focused delivery of radiation energy to the target tissues with intracavitary radiation as well as external beam with supervoltage radiation, multiple portals, and the improved shielding of adjacent normal structures. Radiotherapy’s adverse effects may be decreased with a combination of the following:

  • Multidirectional, sharply collimated beams
  • Computer-assisted dosimetry
  • More stable intracavitary applicators
  • Extended intervals between fractionated doses and a lower dose per fraction

Epidemiology

More than 200,000 new cases of prostate, cervical, rectal, testicular, bladder, and endometrial cancer are diagnosed each year. Approximately 50% of these patients require radiation therapy.

Acute radiation-induced injury to the GI mucosa occurs in virtually all patients undergoing radiation therapy. In more than 80% of patients, treatment can control the symptoms of tenesmus, diarrhea, and hematochezia. The use of antispasmodics, analgesics, and antidiarrheal agents combined with intravenous (IV) fluid replacement are often adequate to treat patients with acute radiation enteritis and proctitis.

In a small number of patients, the severity of symptoms requires cessation of radiation therapy. This occurs most commonly in patients who are receiving concomitant chemotherapy or in those at high risk to develop radiation enteritis prior to initiation of therapy.

Approximately 5-15% of patients who receive abdominal or pelvic radiotherapy develop pronounced chronic radiation enteritis. Up to 50% of patients with severe chronic radiation enteropathy require surgical intervention. In patients who receive postoperative radiotherapy, as many as 30-40% experience chronic diarrhea. More than 1 million patients in the United States may have bowel dysfunction related to radiotherapy.

Abayomi et al investigated the incidence of chronic radiation enteritis in 117 women who had undergone radiotherapy for cervical or endometrial cancer.[17] They also sought to determine whether radiation level or cancer stage was associated with an increased risk for enteritis. In response to a questionnaire relating to bowel problems and quality of life, 47% of patients had scores indicating the presence of chronic radiation enteritis. Although scores did not significantly correlate with radiation dose or cancer stage, the investigators determined that scores indicative of chronic radiation enteritis were most prevalent among younger women and among patients who had been treated for cervical cancer.

Prognosis

Surgical procedures on radiated intestine carry a morbidity of 12-65% and a mortality of 2-13%. The wide range reflects the diverse surgical procedures used to treat complications of radiation.

Preoperative radiotherapy has been attributed with a reduced cancer-specific mortality compared with postoperative radiotherapy in soft-tissue sarcoma. Additional studies with larger patient numbers are needed.[18]

Factors that adversely affect prognosis after surgery include intestinal leak, surgery for fistula or perforation, and progression of radiation-induced damage after the initial operation.

An anastomotic breakdown incidence as high as 50% has been noted after resection and anastomosis involving diseased segments of bowel in radiation enteritis.

Almost 50% of patients who survive a laparotomy for radiation bowel injury require further surgery for ongoing bowel damage from radiation. A mortality as high as 25% is reported for patients who require a second surgical procedure. The mortality is directly attributable to the radiation enteritis and complications of treatment.

In an analysis of 77 patients diagnosed with radiation enteritis or proctitis, Ruiz-Tovar et al compiled various statistics relating to the location, treatment, and outcome of these injuries.[19]  Radiation injury sites were as follows:

  • Ileum, 55 patients (71%)
  • Rectum, 22 patients (29%)

Treatment course was as follows:

  • Medical management, 28 patients (36%)
  • Surgical treatment, 49 patients (64%) - Resection, 41 (53%); bypass, five (6.5%); terminal colostomy, three (4%)
  • Surgical complications, seven patients (9%)
  • Surgical mortality, three patients (4%)
  • Recurrence of radiation-related illness, 12 patients (16%)
  • Survival rate (excluding mortality from tumoral progression) at 5 years, 90%; at 10 years, 83%
 

Presentation

History and Physical Examination

Acute radiation enteritis occurs in almost all patients undergoing pelvic and abdominal radiation therapy. The degree of symptom severity varies, with approximately 15-20% of patients requiring an altered course of therapy. The most common symptoms are as follows:

  • Cramping abdominal pain
  • Tenesmus
  • Nausea
  • Vomiting
  • Anorexia
  • Diarrhea
  • Hematochezia
  • Fever

The most common clinical finding is generalized abdominal tenderness without peritoneal signs. Rarely, severe acute enteritis is associated with massive hematochezia or bowel perforation.

The clinical symptoms and findings of chronic radiation enteropathy may be difficult to attribute to prior radiation therapy. Clinical manifestations may appear after months or years of subclinical progression. An awareness of the patient’s radiation history and knowledge of the clinical signs and symptoms of the phases of radiation-induced injury enteritis and proctitis allow for timely investigation and treatment. Overly conservative treatment may be just as harmful to a patient as injudiciously timed surgical procedures may be.

Almost all patients who receive more than 1.5 Gy/day develop acute radiation enteritis, either while undergoing therapy or shortly after completion of treatment. In 5-10% of patients, exposure of intestine to a total dose in excess of 50 Gy results in the development of severe chronic radiation enteritis.

 

Workup

Laboratory Studies

In patients with acute radiation-induced intestinal injury, the complete blood count (CBC) and differential count may be within the reference range. With chronic injury, anemia may be noted because of chronic blood loss and malnutrition.[20] Elevated white blood cell (WBC) counts are observed with small-bowel obstruction and intra-abdominal sepsis because of bowel perforation or necrosis.

Complete metabolic panel results reveal electrolyte abnormalities.

Patients with chronic malnutrition because of malabsorption have abnormal liver function test results and coagulation profiles.

Imaging Studies

In the presence of mild intestinal injury, findings from plain abdominal radiography are nonspecific. Dilated bowel loops with air-fluid levels indicate bowel obstruction. Free air indicates perforation in severe acute or chronic enteropathy, especially in the presence of associated bowel obstruction.

Because most patients have undergone prior surgery, computed tomography (CT) of the abdomen and pelvis is the best study to reveal bowel obstruction. CT may differentiate a partial obstruction from a complete obstruction, as well as define the site of obstruction. Additionally, recurrent malignancy may often be identified. Most patients with obstructive symptoms because of radiation injury present with recurrent, partial obstructions. Patients who present with complete bowel obstructions require surgical exploration and definitive treatment based on the pathology encountered.

Upper gastrointestinal (GI) barium examinations with small intestinal follow-through accurately define the location, extent, and nature of stenotic lesions (see the image below). Mucosal patterns of affected bowel mimic those of inflammatory bowel disease (ie, thickened valvulae conniventes, mural thickening with thumb printing resulting from edema of the submucosa, infiltration of the intestinal wall with fibrotic tissue). Other findings include sinuses and fistulas, variable areas of barium pooling, and rapid intestinal transit of contrast agents.

Contrast study of the small bowel revealing areas Contrast study of the small bowel revealing areas of extensive strictures with a loop of bowel fixed in the pelvis.

Other Tests

Radiation-induced enteric injury leads to extensive intestinal functional abnormalities, resulting in decreased bile acid and vitamin B12 absorption, increased fecal fat excretion, and increased lactose malabsorption. These factors combine to cause rapid small-intestine and whole-gut transit, resulting in chronic diarrhea. Decreased bile salt reabsorption causes a cathartic reaction in the colon, contributing to diarrhea. Bile acid breath tests or direct measurement of bile acids in stool may be used to evaluate the alteration in bile salt metabolism by colonic bacteria.

Selenium-75 homocholic acid taurine (SeHCAT) is a synthetic conjugated bile acid that is resistant to deconjugation and dehydroxylation. SeHCAT may be used to evaluate the active transport of bile acids in the terminal ileum. Patients with poor SeHCAT absorption and retention respond well to cholestyramine treatment. SeHCAT may also be used to evaluate the effectiveness of antidiarrheal agents in reducing transit time and in improving bile acid reabsorption.

Endoscopy

Endoscopy is generally avoided in the acute phases of radiation enteritis because of the risk of perforation. Colonoscopy may be necessary to establish a diagnosis or to treat hemorrhage. In these instances, endoscopy is performed cautiously, with minimal bowel insufflation. The intestinal and rectal mucosa is friable and edematous, with areas of superficial ulceration. In severe acute radiation injury, the mucosa may be intensely inflamed, with diffuse duskiness, edema, and extensive ulcerations (see the image below).

Diffuse inflammation and areas of superficial ulce Diffuse inflammation and areas of superficial ulceration observed endoscopically in acute radiation enteritis.

Pale, thin, friable mucosa with prominent submucosal telangiectasias characterizes the endoscopic findings in chronic radiation enteropathy. Smooth, symmetric strictures and areas of ulcerations and fistulas may be identified endoscopically. Bowel-wall biopsy samples are often necessary to differentiate areas of radiation injury from recurrent or de-novo malignancy.

Small-bowel capsule endoscopy is increasingly used to reveal areas of bleeding within the small bowel that are not accessible with traditional endoscopy. Although described in the literature, the use of capsule endoscopy to reveal strictures and fistulas is controversial. The capsule endoscope may become impacted in a stenotic area, risking complete bowel obstruction; therefore, in instances of bowel obstruction, the usefulness of small-bowel capsule endoscopy is limited.

Histologic Findings

Mucosal inflammation with necrosis and ulceration characterize the histologic findings of acute enteritis and colitis. These findings usually appear within 2 weeks after cessation of therapy and gradually resolve over the next few months with mucosal regeneration. The epithelial cells lining the intestinal crypts demonstrate marked enlargement with depletion of mucin and large atypical nuclei.

Despite the intense inflammatory reaction, the general mucosal architecture is preserved, the low nuclear-cytoplasmic ratio is preserved, and no mitotic figures are present. These features help distinguish the radiation-injured intestine from malignancy.

The hallmarks of chronic radiation-induced intestinal injury are as follows:

  • Obliterative arteritis
  • Connective tissue fibrosis
  • Atrophy of the overlying mucosa

The blood vessels in the lamina propria and submucosa are ectatic with intimal fibroplasias, accumulation of foamy macrophages, and hyalin thickening of the vessel walls. All of these changes effectively result in luminal stenosis. Fibrosis of the connective tissue of the submucosa, muscularis propria, and serosa has a hyalinized appearance with large, atypical radiation fibroblasts. The appearance of these cells is typical of, though not pathognomonic for, radiation-induced injury.

Many of the delayed complications of radiation exposure may be attributed to the ischemia related to vascular changes.

Staging

The Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) developed a scoring system for organ-specific radiation-related morbidity according to symptom severity (see Table 1 below).

Table 1. Scoring System for Organ-Specific Radiation-Related Morbidity (Open Table in a new window)

 

Grade 0

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

Signs and symptoms

None

Mild diarrhea, mild cramping, bowel movements 5 times per day, slight rectal discharge or bleeding

Moderate diarrhea and colic, bowel movements >5 times per day, excessive rectal mucus or intermittent bleeding

Obstruction or bleeding requiring surgery

Necrosis, perforation, fistula

Death directly related to late effects of radiation

 

Treatment

Approach Considerations

Most patients initially respond well to conservative therapy; however, recurring symptoms and signs often eventually necessitate surgical intervention. Indications for surgical intervention include the following:

  • To prevent radiation-induced injury to the small bowel
  • To treat complications of radiation-induced injury to the small and large bowel, including perforation, obstruction (the most common presentation of chronic radiation enteritis), fistula, and bleeding (the most common presentation of chronic radiation proctitis)

Debate continues over the timing and extent of surgery for the complications of radiation-induced intestinal injury. Advocates of limited surgical procedures (including bypass procedures and diverting ostomy) suggest that these are safer, with a mortality of 2-10% and a morbidity of 20-30%. Other authors advocate wide resection of affected intestinal segments with anastomosis to the transverse colon. These authors report mortality and morbidity figures similar to those reported for bypass procedures.

The American Society of Colon and Rectal Surgeons (ASCRS) has formulated guidelines for the treatment of chronic radiation proctitis (see Guidelines).[21]

Medical Therapy

Preventive measures

Measures designed to decrease or prevent the occurrence of radiation-induced enteropathy are an integral part of radiation therapy administration. Preventive measures include medical therapies to decrease the effects of radiation on the gastrointestinal (GI) tract. The commonly used methods of prevention include the following:

  • Basic bowel care (including maintenance of adequate hydration) and dietary modifications - Many patients develop transient lactose intolerance
  • Sulfasalazine, 500 mg orally twice daily - This has been shown to help reduce the incidence and severity of radiation-induced enteropathy in patients receiving external beam radiotherapy to the pelvis
  • Amifostine - This is a prodrug that is converted to its intracellular metabolite, WR-1065, which acts as a radioprotectant; intracellular oxidation of WR-1065 yields active metabolites that protect the cell by scavenging free radicals and stabilizing the DNA; amifostine administered intravenously (IV) in a dose of 340 mg/m 2 is proved to decrease the incidence of radiation proctitis in patients receiving standard-dose radiotherapy for rectal cancer; it has also been used as an intrarectal foam enema (ProctoFoam) with variable results [22]
  • Sucralfate, orally and as enemas - This has been proposed as a mucosal protective agent for prevention of radiation-induced enteropathy, with variable results
  • Glutamine - This is the preferred metabolic fuel for enterocytes; it may be an effective radioprotectant [23]

Prebiotics (eg, inulin and fructo-oligosaccharide) have been suggested as a possible means of helping to prevent acute radiation enteritis in patients with gynecologic cancer.[24]  Scartoni et al found that a zinc-based nutritional supplement to which prebiotics, tyndalized probiotics, and vitamins had been added was a safe and feasible means of protecting against radiation-induced diarrhea in patients undergoing pelvic radiotherapy.[25]

Medical control of symptoms

The following medical treatments aim to control the symptoms of radiation-induced enteritis and proctitis:

  • Adequate hydration
  • Antidiarrheals – Loperamide is a commonly used first agent; if diarrhea is not adequately controlled with the use of loperamide, octreotide at a dosage of 100 μg subcutaneously (SC) twice daily has been shown to be effective; cholestyramine also decreases the frequency of diarrhea
  • Antiemetic medication
  • Sucralfate enemas (used to decrease the bleeding associated with chronic radiation-induced proctitis)
  • Sulfasalazine, orally and as enemas (decreases the symptoms of tenesmus, abdominal cramping, and diarrhea associated with radiation enteritis and proctitis)
  • Hyperbaric oxygen therapy (considered in the treatment of intractable radiation proctitis, prior to surgical intervention)

Modification of radiotherapy

Modification in the delivery of radiotherapy may decrease radiation-induced bowel injury. Some of these techniques currently practiced include the following:

  • Multiple-field conformal therapy with prior three-dimensional (3D) planning
  • Pretreatment small-bowel contrast studies (to evaluate the position of the small bowel within the abdominopelvic cavity)
  • Methods to relocate the small bowel from the pelvic cavity into the abdominal cavity - Prone or Trendelenburg positioning; bladder distention; abdominal wall compression; open table-top device (belly board); temporary pneumoperitoneum

Nonsurgical bleeding control

Nonsurgical endoscopic interventions are commonly used to treat recurrent bleeding associated with chronic radiation proctitis.

Endoscopic argon plasma coagulation (APC) is the endoscopic technique of choice to control mucosal bleeding due to chronic radiation proctitis.[26, 27, 28] Compared with laser or heater probe therapy, APC has a limited depth of penetration, resulting in a lower risk of perforation. Multiple treatments are usually required, but bleeding is successfully controlled in 85-90% of patients.

The neodymium:yttrium-aluminum-garnet (Nd:YAG) laser has been used to achieve hemostasis, but less successfully than APC. Some evidence suggests that radiofrequency ablation (RFA) is effective and safe for chronic radiation proctitis, but long-term data are limited.[29]  

Topical formalin therapy controls bleeding inexpensively and effectively. Two main techniques are used to apply formalin to the bleeding mucosa. In the first, formalin (50-mL aliquots of 4% solution for a total volume of 400 mL) may be instilled in the rectum via a proctoscope. The formalin remains in contact with the rectal mucosa for 30 seconds, followed with copious saline irrigation between applications. After each treatment and lavage, the rectal mucosa is examined for cessation of bleeding. This technique is used for diffuse bleeding from the mucosal surface.

In the alternative technique, formalin-soaked gauze is directly applied to an area of localized bleeding. Blind instillation of formalin via a rectal tube is not advised because of the risk of perforation. Anal-fissure formation is a common complication after formalin therapy. Hence, care must be taken with both techniques to protect the perianal skin.

General Principles of Surgical Management

Choice of procedure

Surgical intervention may prevent or treat the complications of enteritis or proctitis. Preventive surgical procedures are performed in conjunction with the primary surgical procedure for cancer resection.[30] Patients are candidates for a primary surgical preventive procedure if they do not require abdominal or pelvic surgery for treatment of malignancy yet are at high risk to develop radiation-induced injury.

Surgical intervention is reserved for the most refractory cases and for complications such as obstruction, perforation, fistula, or hemorrhage. Operative treatment is individualized on the basis of the following:

  • Patient’s overall condition
  • Preoperative assessment of the lesion
  • Technical feasibility of performing the optimal surgical procedure
  • Intraoperative findings

Typically, patients with complicated small-bowel radiation injuries are best treated with resection if feasible, bypass if necessary, and diversion or exclusion of the affected segment as a last resort. Patients with complicated colorectal radiation injuries are best treated with resection and primary anastomosis, if possible. Proximal diversion should be performed if impaired healing of the anastomosis is a concern. Repair of fistulas may be performed via a transabdominal or perineal approach.

Preoperative evaluation and treatment

The preoperative evaluation for treatment of complications of radiation-induced intestinal injury reveals patients who are surgical candidates. Their overall condition is optimized prior to surgery, and surgical treatment is appropriately individualized in accordance with the severity and extent of the injury.

Radiation enteritis complications

Decompression of small bowel obstruction with placement of a nasogastric tube may be performed.

IV hydration and correction of electrolyte imbalance may be provided. Patients with small-bowel obstruction may be significantly dehydrated and have severe electrolyte abnormalities.

Unless an operation is done on an emergency basis, preoperative radiologic evaluation with small-bowel follow-through and barium enema should be performed. These studies may reveal synchronous lesions that are common in radiation enteritis and may influence the planned operative procedure.

Radiologic and endoscopic evaluation may exclude recurrent or primary malignancy. Radiation-induced strictures are longer, with gradual tapering to the point of stenosis with edematous, speckled-appearing mucosa. In contrast, malignant strictures have distinct separation from healthy intestine, and the mucosa and bowel wall have a heterogeneous appearance. These radiologic findings are not pathognomonic, and the tissue may have to be obtained endoscopically to differentiate malignant from radiation-induced strictures. Fistulas may also represent areas of recurrent or de-novo malignancy that must be differentiated from radiation-induced injury.

Comorbid conditions should be corrected or treated. Perioperative risks may be reduced through correction of severe anemia and optimization of nutritional status.

Radiation proctitis complications

Exclude recurrent local or disseminated cancer through endoscopic evaluation of tissue biopsy samples from the area of the fistula or stricture.

Evaluate the patient for suitability for major pelvic surgery. Patients who are debilitated may not be candidates for resectional procedures, which may lead to significant blood loss and the risk of anastomotic leak. These patients may be better served by a proximal diverting colostomy or a local fistula repair procedure.

Perform anal manometry to evaluate rectal compliance, anal function, and continence. The presence of a noncompliant rectum is an indication for a resectional procedure rather than a local fistula repair. Incontinence is an indication for a proximal colostomy rather than resection or repair.

Determine the surgical approach (dictated by the location of the fistula or stricture with respect to the levator ani muscle). High lesions are approached transabdominally, while low fistulas may be repaired via a perineal approach. Low-lying strictures may be addressed similarly with repeat anal dilations or transanal strictureplasty. Larger fistulas or those associated with strictures or significant proctitis require a transabdominal approach with resection.

Surgery for Radiation Enteritis

Prevention

Surgical procedures for prevention of radiation enteritis (see Table 2 below) are based on the principles of reperitonealization and abdominopelvic partitioning.

Table 2. Surgical Procedures to Prevent Radiation Enteritis (Open Table in a new window)

Native Tissue

Prosthetic Materials

 

 

Reperitonealization procedures

Omentum-based procedures

Peritoneum and posterior rectus sheath

Omental transposition flap

Synthetic pelvic mold (spacer)

Uterine broad ligaments

Omentopexy - Omental apron or envelope

Saline-filled tissue expanders

Bladder

Omental hammock or sling

Absorbable mesh sling

With respect to abdominopelvic partitioning, surgical preventive procedures are used to exclude the mobile small bowel from the pelvic cavity, keeping it away from the area of maximal irradiation. Native tissue or prosthetic material may be used to create a partition between the abdominal and pelvic cavities or to enclose and contain the small bowel within the abdomen.

In reperitonealization procedures, native tissue (eg, peritoneum, bladder, uterine broad ligaments) may be used to create a separation between the abdominal and pelvic cavities. In omental-based procedures, an omental flap based on the left gastroepiploic pedicle is used to create the partition and to contain the small bowel within the abdominal cavity.

The absorbable mesh sling procedure is performed most often (of the operations that use prosthetic materials to exclude the small bowel from the pelvic cavity). Procedures performed less often use pelvic space–occupying devices to displace the small-bowel loops.

Technical considerations

Postoperative adhesions result in fixation of the small bowel, especially within the postoperative pelvis. The limited mobility of this bowel makes it more susceptible to radiation injury. Multiple surgical techniques to exclude the small bowel from the pelvis have been described in the literature. Typically, these procedures are performed with the primary surgical procedure for the malignancy. Occasionally, patients who do not require surgery to treat the primary malignancy still require a small bowel exclusion procedure, because they are at high risk of developing radiation-induced intestinal injury.

Small-bowel exclusion from the pelvis is best achieved using the omentum. Various techniques have been reported in the literature, three of which are commonly performed (see below).

In 1984, Russ et al described the omental transposition flap procedure. An omental pedicle flap based on the left gastroepiploic vessels is placed along the left paracolic gutter and sutured into place. The remainder of the omental bulk is packed into the pelvic cavity, effectively excluding the small bowel from occupying this space and providing protection from radiation injury (see the image below).

Omental transposition flap based on left gastroepi Omental transposition flap based on left gastroepiploic vascular bundle is sutured in place along the left paracolic gutter, and the omental bulk is packed into the pelvic cavity.

In 1985, DeLuca and Ragins described the omental envelope technique.[9] The omentum is draped over the small bowel as an apron. The lower edge of the omentum is sutured to the posterior abdominal wall at the level of the sacral promontory. The lateral borders are sutured to the ascending and descending colon (see the image below). This procedure is also known as abdominopelvic omentopexy .

Omental envelope is created by draping the omentum Omental envelope is created by draping the omentum over the small bowel and suturing the lateral edges to the peritoneum in the paracolic gutters. The lower edge is sutured to the posterior abdominal wall at the level of the sacral promontory.

In 1995, Choi and Lee described the omental pedicle hammock technique.[11] An omental pedicle based on the left gastroepiploic vessels is created and sutured circumferentially to the parietal peritoneum at the level of the sacral promontory and umbilicus. This creates a sling, or hammock, which contains the bowel and prevents it from entering the pelvis (see the image below).

An omental pedicle based on the left gastroepiploi An omental pedicle based on the left gastroepiploic vessels is sutured circumferentially to the parietal peritoneum at the level of the sacral promontory and umbilicus. This creates a sling, or hammock, which contains the bowel and prevents it from entering the pelvis.

Reperitonealization procedures use native tissue to isolate the pelvis from the abdominal cavity. The tissue is seldom adequate or strong enough to achieve adequate exclusion; thus, these are not commonly performed procedures.

In 1979, Freund et al described a technique of suturing the anterolateral peritoneum to the bladder to the posterior retroperitoneal tissues.[8] In women, the uterus and broad ligaments may be used in addition to the posterior tissue. Chen et al described the approximation of the peritoneum and the posterior rectus sheath to create a peritoneal reconstruction after resection of rectal cancer.

Many patients lack adequate peritoneum and omentum, often because of previous surgical procedures or the presence of extensive omental adhesions that make the tissue impossible to use. Alternative abdominopelvic partitioning procedures using prosthetic materials have been described. Currently, the prosthetic mesh sling procedure is performed most often.

In 1984, Devereux et al first described the absorbable mesh sling technique.[14] A polyglycolic acid or polyglactin mesh sling is sutured in place at the level of the sacral promontory and circumferentially attached to the retroperitoneum and lateral abdominal wall. Anteriorly, the mesh is attached at the level of the umbilicus. The small bowel loops are effectively encased within the mesh sling and separated from the pelvic cavity (see the image below). Care is taken to avoid injury to ureters and iliac vessels.

An absorbable mesh sling is created by suturing a An absorbable mesh sling is created by suturing a Vicryl or Dexon mesh to the sacral promontory, lateral abdominal wall, and anterior abdominal wall at the level of the umbilicus. Within this mesh sling, the small bowel loops are contained and held out of the pelvic cavity.

In 1979, Lavery et al reported the use of gauze packs encased in a latex dam to protect the abdominal viscera during high-dose radiotherapy for osteogenic sarcoma of the iliac bone.[12] Placement and removal of the pack required additional surgical procedures.

In 1983, Sugarbaker described the use of a silicone breast implant covered with a mesh baffle to fill the pelvis and to exclude the small bowel.[13] Likewise, Durig et al described the use of a solid synthetic pelvic spacer. More recently, Hoffman et al published their experience using saline-filled tissue expanders to occupy the pelvic cavity (see the image below).

Pelvic-space–occupying device. Pelvic-space–occupying device.

Treatment of complications

Surgical procedures to treat radiation enteritis complications (see Table 3 below) are selected on the basis of the extent of the involved bowel, as well as the technical feasibility of completing the procedure.

Table 3. Surgical Procedures to Treat Complications of Radiation Enteritis (Open Table in a new window)

Obstruction

Fistula

Perforation

Hemorrhage

Resection and anastomosis

Resection and anastomosis

Resection and anastomosis

Resection and anastomosis

Bypass of multiple/long strictures

Bypass of fistula area

 

 

Strictureplasty

Diversion with proximal ostomy

 

 

Diversion with proximal ostomy

 

Obstruction is the most common chronic complication affecting the irradiated small bowel. In patients with chronic radiation enteritis who require surgical intervention, 75-80% require treatment of an obstruction. Long or multiple stricture segments may be more appropriately treated with bypass.

Strictureplasty has been reported to successfully treat the obstruction. Strictureplasty involves performing a repair of enterotomies created over irradiated tissue and is associated with a higher risk of leak. Dissecting densely adherent bowel loops free within the pelvis may be impossible without significant risk of creating multiple enterotomies. Bypass of the affected bowel is preferable in these instances as well. Extremely debilitated patients are candidates for a proximal decompressing ostomy.

Fistulas account for 5-10% of irradiated bowel complications that necessitate surgery. Adjacent pelvic structures (ie, bladder, rectum, vagina) are areas in which fistulas often form with small bowel. Surgery entails resection of the involved small bowel up to healthy margins. Primary anastomosis of the divided ends of bowel is performed. The defect in the involved bladder, vagina, or rectum is closed primarily. Diversion of the enteric contents via a proximal ostomy is an option in the presence of a hostile abdomen or in patients who are severely debilitated.

Perforation is a rare complication of delayed effects of radiation and is often associated with obstruction. The treatment of perforation involves resection of the area of perforation with exteriorization of the divided ends of the bowel (if intraperitoneal contamination is extensive). Performing a primary anastomosis may be possible if the area of contamination is localized.

Hemorrhage rarely requires surgical intervention. An area of uncontrolled bleeding that can be localized within the small bowel but cannot be treated conservatively may require surgical resection of the involved bowel segment.

Technical considerations

Certain technical principles are crucial to the success of procedures performed to treat the complications of radiation-induced intestinal injury.

Lysis of adhesions should be limited because of the risk of inadvertent enterotomies and denudation of intestinal serosa. This increases the risk of peritonitis, sepsis, and fistula formation. Intestinal fistulas often form in patients who have undergone laparotomy to treat intestinal obstruction, which developed as a consequence of radiation injury. Enterotomies, serosal injuries, and nonhealing anastomoses in irradiated tissue results in the formation of fistulas.

Intestinal obstruction from dense adhesions of fixed bowel loops within the pelvis is best treated with bypass of the adherent strictured segments. In these patients, excessive attempts to lyse adhesions leads to a high complication rate, including short-bowel syndrome.

Perforation should be treated with resection of the involved segment, because bypass inevitably leads to the complications of fistula, peritonitis, or sepsis.

If resection is performed, at least one end of the anastomosis should include intestine that is located outside the irradiated field. Most often, this is the transverse colon or splenic flexure. Almost 50% of anastomoses that are performed in diseased bowel result in a breakdown because of the poor healing of irradiated tissue.

If the viability of an anastomosis is questionable, preferably, a stoma should be constructed.

Surgery for Radiation Proctitis

Treatment of complications

The rectum, with its fixed position and proximity to the area undergoing treatment, is the most common site of injury following radiation to the pelvis. As such, long-term complications include hemorrhagic proctitis, rectovaginal fistulas, and rectal strictures (see Table 4 below).

Table 4. Surgical Treatment of Radiation Proctitis Complications (Open Table in a new window)

Hemorrhagic Proctitis

 

 

Rectovaginal Fistulas and Strictures

Transabdominal procedures

Perineal procedures

Proctectomy with coloanal anastomosis

Proctectomy with coloanal anastomosis

Transanal flap

Proctectomy with end colostomy

Proctectomy with end colostomy

Transvaginal flap

 

Colonic J-pouch-anal anastomosis

 

 

Ileocecal reservoir

 

 

Sigmoid colon onlay patch (Bricker-Johnston)

 

Most often, hemorrhagic proctitis is adequately treated with endoscopic APC or Nd:YAG laser treatment, heater probe coagulation, or application of formalin.[31] Patients with recalcitrant bleeding from the rectal mucosa may undergo proctectomy. This is a morbid procedure in the irradiated pelvis and is associated with significant blood loss. Primary anastomosis should be performed, if possible. If technically difficult, an end colostomy may have to be created. Creation of a proximal ostomy without resection has been reported in the literature; however, this procedure rarely controls the bleeding, since the diseased rectum remains in place.

Rectovaginal fistulas and rectal strictures are a common problem with irradiation. The treatment approach is transabdominal for high fistulas and perineal for low fistulas. The optimal surgical procedure is resection of the fistula and the affected bowel segment, followed with primary colorectal anastomosis. The vaginal defect is repaired or allowed to heal through secondary intention. Patients who are debilitated may benefit from a proximal diverting colostomy. Strictures are treated with resection and primary anastomosis, if possible. Proximal colostomy is an option for severely debilitated patients or in patients who are not good surgical candidates.

Technical considerations

In low-risk patients, rectal strictures and fistulas are best treated with proctectomy with reconstruction. The sigmoid and descending colon is mobilized, the rectum is resected down to the pelvic floor, and dissection within the rectovaginal septum is undertaken to separate the vagina from the rectum. The left colon and splenic flexure are adequately mobilized to obtain sufficient bowel length. The left colic artery and the inferior mesenteric vein at the inferior border of the pancreas are ligated to allow for the mobilization. Preserving the blood supply to the left colon is important. The distal transverse colon should be used as the proximal limb if the blood supply is questionable.

To reconstruct, the descending colon is anastomosed to the rectal remnant just proximal to the dentate line. The anastomosis is performed in an end-to-side manner using a stapling device. A colonic J pouch may be created to allow for improved fecal reservoir capacity. Stapling devices are used to create the colonic reservoir from 5- to 6-cm segments of the colon. The pouch is then either handsewn or stapled to the anus.

If a concomitant high vaginal fistula was resected, the vaginal vault is repaired in layers and omentum is interposed between the areas of resected tissue and anastomosis.

A proximal diverting colostomy may be created if healing of the anastomosis is a concern. The stoma is closed in approximately 3 months, once contrast imaging studies have demonstrated satisfactory healing of the anastomosis or J-pouch reservoir.

Patients who are not candidates for extensive resection procedures benefit from undergoing a proximal diverting colostomy.

Rectovaginal fistulas and strictures located in the distal rectum or anal canal are treated via perineal approaches.

The transanal technique is performed with the patient in jackknife prone position. A trapezoid flap of mucosa, submucosa, and circular muscle is mobilized for several centimeters above the fistula. To ensure adequate blood supply, the width of the base of the flap is twice the width of the apex. The fistula tract is excised and the edges are debrided. The flap is advanced to cover the defect and sutured in place, approximating the muscularis and the mucosa in two layers using long-lasting absorbable suture material. The vaginal side of the fistula is left open to permit drainage.

Transvaginal repair is performed in the dorsal lithotomy position. The vaginal mucosa is incised around the fistula and mobilized circumferentially. The fistula tract is excised and the tissue is debrided. A purse-string suture is placed around the fistula opening to invert the opening toward the rectum, and the vaginal mucosa is closed.

A transperineal approach follows the same principles of excision of the fistula tract, closure of the defect in layers without tension, and possible incorporation of well-vascularized tissue into the repair. A portion of the bulbocavernosus muscle or an island of vulvar skin and adipose tissue (Lehoczky island flap) may be used to close the defect created by the resected area of fistula tract.

The Bricker-Johnston onlay sigmoid patch procedure is rarely used to treat rectovaginal fistula. The fistula tract and surrounding rectal wall is resected. The mobilized sigmoid colon is anastomosed to this area of rectal wall.

Complications

Factors that contribute to postoperative complications include the following:

  • Poor nutritional status
  • More than one laparotomy prior to radiation
  • Short interval (< 12 months) between radiation and surgical intervention

Surgery on irradiated tissue may lead to the following severe complications:

  • Significant blood loss
  • Inadvertent enterotomies
  • Fistula formation
  • Extensive bowel resection resulting in short-bowel syndrome
  • Creation of blind loops because of excessively long bypassed segments
  • Nonhealing of anastomoses performed on irradiated tissue
  • Anastomotic leakage with peritonitis and sepsis
 

Guidelines

ASCRS Guidelines for Chronic Radiation Proctitis

In October 2018, the American Society of Colon and Rectal Surgeons (ASCRS) issued clinical practice guidelines for the treatment of chronic radiation proctitis (CRP).[21] Recommendations included the following:

  • A disease-specific history and physical examination should be performed, emphasizing the degree and duration of bleeding.
  • Prophylactic measures, such as pedicled omental flap and tissue expander implant, have been described to decrease the incidence of radiation proctitis. These techniques are insufficiently evaluated and are not routinely recommended.
  • Formalin application is an effective treatment for bleeding in patients with CRP.
  • Sucralfate retention enemas are a moderately effective treatment for rectal bleeding resulting from CRP. 
  • Short-chain fatty acid (SFCA) enemas are not effective in preventing or treating chronic hemorrhagic radiation proctitis and are not recommended.
  • Alternative treatments such as mesalamine, ozonetherapy, and metronidazole have not been adequately evaluated in treating radiation proctitis and are not recommended.
  • Endoscopic argon beam plasma coagulation (APC) is a safe and effective treatment for rectal bleeding induced by CRP.
  • Hyperbaric oxygen therapy is an effective treatment modality for reducing bleeding in patients with CRP.
  • Endoscopic bipolar electrocoagulation, radiofrequency ablation (RFA), neodymium:yttrium-aluminum-garnet (Nd:YAG) laser, and cryotherapy are alternative treatments of rectal bleeding from CRP that have been insufficiently evaluated and are thus not recommended.