Gastrointestinal Complications (PDQ®): Supportive care - Health Professional Information [NCI]

National Cancer Institute logo  

This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER

Gastrointestinal Complications

Purpose of This PDQ Summary

This PDQ cancer information summary provides comprehensive, peer-reviewed information for health professionals about the pathophysiology and treatment of gastrointestinal complications, including constipation, impaction, bowel obstruction, diarrhea, and radiation enteritis. This summary is reviewed regularly and updated as necessary by the PDQ Supportive and Palliative Care Editorial Board.

Information about the following is included in this summary:

  • Etiology.
  • Diagnosis.
  • Treatment.

This summary is intended as a resource to inform and assist clinicians and other health professionals who care for cancer patients during and after cancer treatment. It does not provide formal guidelines or recommendations for making health care decisions. Information in this summary should not be used as a basis for reimbursement determinations.

This summary is also available in a patient version, which is written in less technical language, and in Spanish.

Overview

Gastrointestinal complications (constipation, impaction, bowel obstruction, diarrhea, and radiation enteritis) are common problems for oncology patients. The growth and spread of cancer, as well as its treatment, contribute to these conditions.

Constipation is the slow movement of feces through the large intestine that results in the passage of dry, hard stool. This can result in discomfort or pain.[1] The longer the transit time of stool in the large intestine, the greater the fluid absorption and the drier and harder the stool becomes.

Inactivity, immobility, or physical and social impediments (particularly inconvenient bathroom availability) can contribute to constipation. Depression and anxiety caused by cancer treatment or cancer pain can lead to constipation. Perhaps the most common causes of constipation are inadequate fluid intake and pain medications; however, these causes are manageable.

Constipation may be annoying and uncomfortable, but fecal impaction can be life-threatening. Impaction refers to the accumulation of dry, hardened feces in the rectum or colon. The patient with a fecal impaction may present with circulatory, cardiac, or respiratory symptoms rather than with gastrointestinal symptoms.[2] If the fecal impaction is not recognized, the signs and symptoms may progress and result in death.

In contrast to constipation or impaction, an intestinal obstruction is a partial or complete occlusion of the bowel lumen by a process other than fecal impaction. Intestinal obstructions can be classified by three means: the type of obstruction, the obstructing mechanism, and the part of the bowel involved.

Structural disorders, such as intraluminal and extraluminal bowel lesions caused by primary or metastatic tumor, postoperative adhesions, volvulus of the bowel, or incarcerated hernia, affect peristalsis and the maintenance of normal bowel function. These disorders can lead to total or partial obstruction of the bowel. Patients who have colostomies are at special risk of developing constipation. If stool is not passed on a regular basis (once a day to several times a day), further investigation is warranted. A partial or complete blockage may have occurred, particularly if no flatus has been passed.[3]

Diarrhea can occur throughout the continuum of cancer care, and the effects can be physically and emotionally devastating. Although less prevalent than constipation, diarrhea remains a significant symptom burden for people with cancer. Diarrhea can alter dietary patterns, trigger dehydration, create electrolyte imbalance, impair function, cause fatigue, impair skin integrity, limit activity, and in some cases, be life threatening. Furthermore, diarrhea can lead to increased caregiver burden. Specific definitions of diarrhea vary widely. Acute diarrhea is generally considered to be an abnormal increase in stool liquid that lasts more than 4 days but less than 2 weeks. Another definition suggests that diarrhea is an increase in stool liquidity (>300 mL of stool) and frequency (the passage of more than three unformed stools) during a 24-hour period.[4] Diarrhea is considered chronic when it persists longer than 2 months.

Radiation enteritis is a functional disorder of the large and small bowel that occurs during or after a course of radiation therapy to the abdomen, pelvis, or rectum.

The large and small bowel are very sensitive to ionizing radiation. Although the probability of tumor control increases with the radiation dose, so does the damage to normal tissues. Acute side effects to the intestines occur at approximately 10 Gy. Because curative doses for many abdominal or pelvic tumors range between 50 and 75 Gy, enteritis is likely to occur.[5]

Management of constipation, impaction, bowel obstruction, diarrhea, and radiation enteritis in the pediatric patient varies from management in the adult patient and should be adjusted accordingly.

References:

1. Culhane B: Constipation. In: Yasko J, ed.: Guidelines for Cancer Care: Symptom Management. Reston, Va: Reston Publishing Company, Inc., 1983, pp 184-7.
2. Wright BA, Staats DO: The geriatric implications of fecal impaction. Nurse Pract 11 (10): 53-8, 60, 64-6, 1986.
3. Hampton BG, Bryant RA, eds.: Ostomies and Continent Diversions: Nursing Management. St. Louis, Mo: Mosby Year Book, Inc., 1992.
4. Tuchmann L, Engelking C: Cancer-related diarrhea. In: Gates RA, Fink RM, eds.: Oncology Nursing Secrets. 2nd ed. Philadelphia, Pa: Hanley and Belfus, 2001, pp 310-22.
5. Perez CA, Brady LW, eds.: Principles and Practice of Radiation Oncology. 3rd ed. Philadelphia, Pa: Lippincott-Raven Publishers, 1998.

Constipation

Etiology of Constipation

Common factors that contribute to the development of constipation in the general population are diet, altered bowel habits, inadequate fluid intake, and lack of exercise. Constipation can be a presenting symptom of cancer, or it can occur later as a side effect of a growing tumor or treatment of the tumor. For patients with cancer, additional causative factors are the tumor itself, cancer-related problems, the effects of drug therapy for cancer or for cancer pain, and other concurrent processes such as organ failure, decreased mobility, and depression.[1] Physiologic factors include inadequate oral intake, dehydration, inadequate intake of dietary fiber, or organ failure. Any or all of these factors can occur because of the disease process, aging, debilitation, or treatment. (Refer to the Nausea, Vomiting, Constipation, and Bowel Obstruction in Advanced Cancer section in the PDQ summary on Nausea and Vomiting for more information.)

Causes of Constipation

Medications

  • Chemotherapy (e.g., any agent that can cause autonomic nervous system changes such as vinca alkaloids, oxaliplatins, taxanes, and thalidomide).*
  • Opioids or sedatives.
  • Anticholinergic preparations (e.g., gastrointestinal antispasmodics, antiparkinsonism agents, and antidepressants).
  • Phenothiazines.
  • Calcium- and aluminum-based antacids.
  • Diuretics.
  • Vitamin supplements (e.g., iron and calcium).
  • Tranquilizers and sleeping medications.
  • General anesthesia and pudendal blocks.

Diet

  • Inadequate fluid intake.*

Altered bowel habits

  • Repeatedly ignoring defecation reflex.
  • Excessive use of laxatives and/or enemas.

Prolonged immobility* and/or inadequate exercise

  • Spinal cord injury or compression, fractures, fatigue, weakness, or inactivity (including bedrest).
  • Intolerance with respiratory or cardiac problems.

Bowel disorders

  • Irritable colon, diverticulitis, or tumor.*

Neuromuscular disorders (disruption of innervation leads to atony of the bowel)

  • Neurological lesions (cerebral tumors).
  • Spinal cord injury or compression.*
  • Paraplegia.
  • Cerebrovascular accident with paresis.
  • Weak abdominal muscles.

Metabolic disorders

  • Hypothyroidism and lead poisoning.
  • Uremia.*
  • Dehydration.*
  • Hypercalcemia.*
  • Hypokalemia.
  • Hyponatremia.

Depression

  • Chronic illness.
  • Anorexia.
  • Immobility.
  • Antidepressants.

Inability to increase intra-abdominal pressure

  • Emphysema.
  • Any neuromuscular impairment of the diaphragm or abdominal muscles.
  • Massive abdominal hernias.

Atony of muscles

  • Malnutrition.
  • Cachexia, anemia, or carcinoma.*
  • Senility.

Environmental factors

  • Inability to get to the bathroom without assistance.
  • Unfamiliar or hurried environment.
  • Excess heat leading to dehydration.
  • Change in bathroom habits (e.g., use of a bedpan).
  • Lack of privacy.

Narrowing of colon lumen

  • Related to scarring from radiation therapy, surgical anastomosis, or compression from growth of extrinsic tumor.

*Frequently seen in oncology patients.

Constipation is frequently the result of autonomic neuropathy caused by the vinca alkaloids, taxanes, and thalidomide. Other drugs such as opioid analgesics or anticholinergics (antidepressants and antihistamines) may lead to constipation by causing decreased sensitivity to the defecation reflexes and decreased gut motility. Since constipation is common with the use of opioids, a bowel regimen should be initiated at the time opioids are prescribed and continued for as long as the patient takes opioids. Opioids produce varying degrees of constipation, suggesting a dose-related phenomenon. One study suggests that clinicians should not base laxative prescribing on the opioid dose, but rather should titrate the laxative according to bowel function. Lower doses of opioids or weaker opioids, such as codeine, are just as likely to cause constipation.[2] (Refer to the Side Effects of Opioids section in the PDQ summary on Pain for more information.)

Other diseases, such as diabetes (with autonomic neuropathy) and hypothyroidism, may cause constipation. Metabolic disorders, such as hypokalemia and hypercalcemia, also predispose cancer patients to developing constipation. Once these disorders are corrected, constipation should subside.[1]

Assessment of Constipation

A normal bowel pattern is having at least three stools per week and no more than three per day; however, these criteria may be inappropriate for cancer patients.[1,3] Constipation should be viewed as a subjective symptom involving the complaints of decreased frequency with incomplete passage of dry, hard stool. A thorough history of the patient's bowel pattern, diet changes, and medications along with a physical examination can identify possible causes of constipation. The evaluation should also include assessment of associated symptoms such as distention, flatus, cramping, or rectal fullness. A digital rectal examination should always be done to rule out fecal impaction at the level of the rectum. A test for occult blood will be helpful in determining a possible intraluminal lesion. A thorough examination of the gastrointestinal tract is necessary if cancer is suspected.[4]

The following questions may provide a useful assessment guide:

1. What is normal for the patient: frequency, amount, and timing?
2. When was the last bowel movement? What was the amount, consistency, and color? Was blood passed with it?
3. Has the patient been having any abdominal discomfort, cramping, nausea or vomiting, pain, excessive gas, or rectal fullness?
4. Does the patient regularly use laxatives or enemas? What does the patient usually do to relieve constipation? Does it usually work?
5. What type of diet does the patient follow? How much and what type of fluids are taken on a regular basis?
6. What medication (dose and frequency) is the patient taking?
7. Is this symptom a recent change?
8. How many times a day is flatus passed?

Physical assessment will determine the presence or absence of bowel sounds, flatus, or abdominal distention. Patients with colostomies should also be assessed for constipation. Dietary habits, fluid intake, activity levels, and use of opioids in these patients should be assessed. Irrigation of the colostomy should be monitored for proper technique.

Management of Constipation

Comprehensive management of constipation includes prevention (if possible), elimination of causative factors, and judicious use of laxatives. Some patients can be encouraged to increase dietary fiber (fruits; green, leafy vegetables; 100% whole-grain cereals and breads; and bran) and to increase fluid intake to one-half ounce per pound of body weight daily (if not contraindicated by renal or heart disease). (Refer to the PDQ summary on Nutrition in Cancer Care for more information.) A study that involved geriatric patients compared the efficacy, cost, and ease of administration of a natural laxative mixture (raisins, currants, prunes, figs, dates, and prune concentrate) with protocols using stool softeners, lactulose, and other laxatives. Results indicate lower costs, more natural and regular bowel movements, and increased ease of administration with natural laxatives. Even though generalization from these findings is limited by small sample size, additional exploration of natural laxatives in cancer patient populations might be useful.[5] A program for prevention of constipation in cancer patients is described below.

Assessment:

  • Establish the patient's normal bowel pattern and habits (time of day for normal bowel movement, consistency, color, and amount).
  • Explore the patient's level of understanding and compliance relating to exercise level, mobility, and diet (fluid, fruit, and fiber intake).
  • Determine normal or usual use of laxatives, stimulants, or enemas.
  • Determine laboratory values, specifically looking at platelet count.
  • Conduct a physical assessment of the rectum (or stoma) to rule out impaction.

Record bowel movements daily. Commonly used interventions include the following:

  • Encourage patient to increase fluid intake, with a goal of drinking eight 8-oz (240-mL) glasses of fluid daily unless contraindicated.
  • Encourage regular exercise, including abdominal exercises in bed or moving from bed to chair if the patient is not ambulatory.
  • Encourage adequate fiber intake. Experts recommend that:
    • Healthy adults consume 20 g to 35 g of fiber per day (average consumption is 11 g).
    • Children and adolescents consume the number of grams of fiber equal to their age plus 5—for example, a 10-year-old should consume 15 g of fiber per day (10 + 5). This guideline applies until age 18 years; at that time, the adult recommendations should be followed.

      While there are no specific fiber recommendations for cancer patients, they should also be encouraged to eat more high-fiber foods such as fruits (e.g., raisins, prunes, peaches, and apples), vegetables (e.g., squash, broccoli, carrots, and celery), and 100% whole-grain cereals, breads, and bran. Increased fiber intake must be accompanied by increased fluid intake, or constipation may result. High fiber intake is contraindicated in patients at increased risk for bowel obstruction, such as those with a history of bowel obstruction or status postcolostomy.

  • Provide a warm or hot drink approximately one-half hour before time of patient's usual defecation.
  • Provide privacy and quiet time at the patient's usual or planned time for defecation.
  • Provide toilet or bedside commode and appropriate assistive devices; avoid bedpan use whenever possible.

Another approach, shown below in two parts, is adapted from the MD Anderson Cancer Center practice consensus algorithm for the prevention and management of opioid-induced constipation. Copyright 2008 The University of Texas MD Anderson Cancer Center

MD Anderson Cancer Center Algorithm for the Prevention of Opioid-induced Constipation

Unless there are existing alterations in bowel patterns (e.g., bowel obstruction or diarrhea), all patients receiving opioids should be started on a laxative bowel regimen and receive education for bowel management.
1.Stimulant laxative plus stool softener (e.g., Senokot-S [senna 8.6 mg plus docusate 50 mg]), two tablets per day and titrate up (maximum nine tablets per day).
2.Ensure adequate fluids, dietary fiber, and exercise, if feasible.
3.Prune juice followed by warm beverage may be considered.

MD Anderson Cancer Center Algorithm for the Management of Opioid-induced Constipation

1. Assess potential cause of constipation (e.g., recent opioid dose increase, use of other constipating medications, or new bowel obstruction).
2. Increase Senokot-S (or senna and docusate tablets, if using separately), and add one or both of the following:
1.Milk of magnesia oral concentrate (1170/5 mL), 10 mL by mouth 2 to 4 times per day.
2.Polyethylene glycol (MiraLAX), 17 g in 8-oz beverage daily.
3. If no response to above, perform digital rectal examination to rule out low impaction. Continue above steps AND:
1.If impacted: Disimpact manually if stool is soft. If not, soften with mineral oil fleets enema before disimpaction. Follow up with milk of molasses enemas until clear with no formed stools.
2.Consider use of rescue analgesics before disimpaction.
3.If not impacted on rectal examination, patient may still have higher level impaction; if history is appropriate, consider abdominal imaging and/or administer milk of molasses enema with magnesium citrate 8 oz by mouth. Consider bowel management consult.
4. If patient is neutropenic or thrombocytopenic, arrange for bowel management consult.
  • Start one of the following regimens if the patient has not had a stool in 3 days or on the first day that any patient starts taking drugs associated with constipation:
    • Stool softeners (e.g., docusate sodium, 1–2 capsules per day). For opioid-related constipation, stool softeners should be used in combination with a stimulant laxative. Bulk-producing agents are not recommended in a regimen used to counteract the bowel effects of opioids.
    • Two tablets of a senna preparation twice daily.
    • One bisacodyl tablet at bedtime.
    • Milk of magnesia, 30 to 45 mL, if a bowel movement is not achieved in 24 hours after other methods are instituted.
  • If the amount of stool is still inadequate, increase stool softeners up to six capsules per day or a senna preparation (e.g., Senokot) gradually to a maximum of eight tablets (four tablets twice a day); bisacodyl may be increased gradually to three tablets.
  • If the amount of stool is still inadequate, a glycerin or bisacodyl suppository or enema (phosphate/biphosphate, oil retention, or tap water) should be used with caution, especially in patients with neutropenia or thrombocytopenia.

Medical management includes the administration of saline or chemical laxatives, suppositories, enemas, or agents that increase bulk.

Rectal agents should be avoided in cancer patients at risk for thrombocytopenia, leukopenia, and/or mucositis from cancer and its treatment. In the immunocompromised patient, no manipulation of the anus should occur, that is, no rectal examinations, no suppositories, and no enemas. These actions can lead to the development of anal fissures or abscesses, which are portals of entry for infection. Also, the stoma of a patient with neutropenia should not be manipulated.

Medical Agents for Constipation

Bulk producers

  • Bulk producers are natural or semisynthetic polysaccharide and cellulose. They work with the body's natural processes to hold water in the intestinal tract, soften the stool, and increase the frequency of the passage of stool. Bulk producers are not recommended for use in a regimen to counteract the bowel effects of opioids.
  • Onset: 12 to 24 hours (may be delayed up to 72 hours).
  • Caution: Patients should take with two full 8-oz (240-mL) glasses of water and maintain adequate hydration to avoid the risk of developing a bowel obstruction. Avoid administering psyllium with salicylates, nitrofurantoin, and digitalis because psyllium decreases the actions of these drugs. Avoid use if intestinal obstruction is suspected.
  • Use: Effective in managing irritable bowel syndrome.
  • Drugs and dosages:
    • methylcellulose (Cologel): 5 to 20 cc 3 times per day with water.
    • barley malt extract (Maltsupex): Four tablets with meals and at bedtime or 2 tbsp powder or liquid 2 times per day for 3 to 4 days, then 1 to 2 tbsp at bedtime.
    • psyllium: Varies from 1 tbsp to one packet, depending on brand, 1 to 3 times per day.

Saline laxatives

  • The high osmolarity of the compounds in saline laxatives attracts water into the lumen of the intestines. The fluid accumulation alters the stool consistency, distends the bowel, and induces peristaltic movement. Cramps may occur.
  • Onset: 0.5 to 3 hours.
  • Caution: Repeated use can alter fluid and electrolyte balance. Avoid magnesium-containing laxatives in patients with renal dysfunction. Avoid sodium-containing laxatives in patients with edema, congestive heart failure, megacolon, or hypertension.
  • Use: Mostly as a bowel preparation to clear the bowels for rectal or bowel examinations.
  • Drugs and dosages:
    • magnesium sulfate: 15 g in a glass of water.
    • milk of magnesia: 10 to 20 cc if concentrated, 15 to 30 cc if regular.
    • magnesium citrate: 240 cc.
    • sodium phosphate: 4 to 8 g dissolved in water.
    • monobasic and dibasic sodium phosphate (Fleet Phospho-soda): 20 to 40 mL mixed with 4 oz cold water.

Stimulant laxatives

  • Stimulant laxatives increase motor activity of the bowels by direct action on the intestines.
  • Onset: 6 to 10 hours.
  • Caution: Prolonged use of these drugs causes laxative dependency and loss of normal bowel function. Prolonged use of danthron discolors rectal mucosa and discolors alkaline urine red. Bisacodyl must be excreted in bile to be active and is not effective with biliary obstruction or diversion. Avoid bisacodyl with known or suspected ulcerative lesions of the colon. These medications may cause cramping.
  • Drug interactions: Avoid taking bisacodyl within 1 hour of taking antacids, milk, or cimetidine because they cause premature dissolving of the enteric coating, which results in gastric or duodenal stimulation. There is an increased absorption of danthron when it is given with docusate.
  • Use: To evacuate bowel for rectal or bowel examinations. Most of the stimulant laxatives act on the colon.
  • Drugs and dosages:
    • danthron: 37.5 to 150 mg with evening meal or 1 hour after evening meal.
    • calcium salts of sennosides: 12 to 24 mg at bedtime; senna: Senolax, Seneson, or Black-Draught (two tablets); Senokot (two tablets or 10–15 cc at bedtime).
    • bisacodyl: 10 to 15 mg swallowed whole, not chewed, or a 10-mg suppository.

Lubricant laxatives

  • Lubricant laxatives lubricate intestinal mucosa and soften stool.
  • Caution: Administer on empty stomach at bedtime. Mineral oil prevents absorption of oil-soluble vitamins and drugs. With older patients, aspiration potential suggests that mineral oil should be avoided because it can cause lipid pneumonitis. It can interfere with postoperative healing of anorectal surgery. Avoid giving with docusate sodium. Docusate sodium causes increased systemic absorption of mineral oil.
  • Use: Prophylactically to prevent straining in patients for whom straining would be dangerous.
  • Drugs and dosages:
    • mineral oil: 5 to 30 cc at bedtime.

Fecal softeners

  • Fecal softeners promote water retention in the fecal mass, thus softening the stool. Up to 3 days may pass before an effect is noted. Stool softeners and emollient laxatives are of limited use because of colonic resorption of water from the forming stool.
  • Fecal softeners should not be used as the sole regimen but may be useful given in combination with stimulant laxatives.
  • Caution: May increase the systemic absorption of mineral oil when administered together.
  • Use: Prophylactically to prevent straining. Most beneficial when stool is hard.
  • Drugs and dosages:
    • docusate sodium: 50 to 240 mg taken with a full glass of water.
    • docusate calcium: 240 mg each day until bowel movement is normal.
    • docusate potassium: 100 to 300 mg each day until bowel movement is normal; should increase daily fluid intake.
    • Poloxamer 188: 188 mg (480 mg at bedtime).

Lactulose (Cholac, Cephulac)

  • Lactulose is a synthetic disaccharide that passes to the colon undigested. When it is broken down in the colon, it produces lactic acid, formic acid, acetic acid, and carbon dioxide. These products increase the osmotic pressure, thus increasing the amount of water held in the stool, which softens the stool and increases the frequency of passage.
  • Onset: 24 to 48 hours.
  • Caution: Excessive amounts may cause diarrhea with electrolyte losses. Avoid giving to patients with acute abdomen, fecal impaction, or obstruction.
  • Dosage: 15 to 30 cc each day (contains 10–20 g of lactulose).

Polyethylene glycol and electrolytes (Golytely, Colyte)

  • Five packets are mixed with 1 gallon (3.785 L) of tap water and contain the following: polyethylene glycol (227.1 g), sodium chloride (5.53 g), potassium chloride (2.82 g), sodium bicarbonate (6.36 g), and sodium sulfate (anhydrous, 21.5 g). Do not add flavorings. Serve chilled to improve palatability. Can be stored up to 48 hours in the refrigerator.
  • Use: To clear bowel with minimal water and sodium loss or gain.

Opioid antagonists (naloxone, methylnaltrexone)

  • CAUTION: ADMINISTER ONLY IF OTHER DRUGS HAVE FAILED.
  • Subcutaneous methylnaltrexone, 0.15 mg per kilogram of body weight, can be administered daily or every other day to treat opioid-induced constipation. In a study of palliative care patients, including those with cancer and non-cancer etiologies, approximately one-half of patients defecated within 4 hours of receiving the injection, with 30% of patients having a bowel movement within the first 30 minutes.
  • In two studies of palliative care patients—one a single-dose trial and the other a 2-week every-other-day-dose trial—there was no evidence of withdrawal or other central effects of the opioid, and pain scores remained unchanged.[6,7]
  • Caution: This drug is contraindicated in patients with bowel obstruction.
  • The most common side effects are dizziness, nausea, abdominal pain, flatulence, and diarrhea.
  • A study of prolonged-released naloxone in an oxycodone:naloxone ratio of 2:1 (average results of 40:20 mg, 60:30 mg, and 80:40 mg oxycodone:naloxone combination relative to placebo) demonstrated improved bowel function without reversal of analgesia.[8]

Current Clinical Trials

Check NCI's PDQ Cancer Clinical Trials Registry for U.S. supportive and palliative care trials about constipation, impaction, and bowel obstruction that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Portenoy RK: Constipation in the cancer patient: causes and management. Med Clin North Am 71 (2): 303-11, 1987.
2. Bennett M, Cresswell H: Factors influencing constipation in advanced cancer patients: a prospective study of opioid dose, dantron dose and physical functioning. Palliat Med 17 (5): 418-22, 2003.
3. McShane RE, McLane AM: Constipation. Consensual and empirical validation. Nurs Clin North Am 20 (4): 801-8, 1985.
4. Bruera E, Suarez-Almazor M, Velasco A, et al.: The assessment of constipation in terminal cancer patients admitted to a palliative care unit: a retrospective review. J Pain Symptom Manage 9 (8): 515-9, 1994.
5. Beverley L, Travis I: Constipation: proposed natural laxative mixtures. J Gerontol Nurs 18 (10): 5-12, 1992.
6. Thomas J, Karver S, Cooney GA, et al.: Methylnaltrexone for opioid-induced constipation in advanced illness. N Engl J Med 358 (22): 2332-43, 2008.
7. Portenoy RK, Thomas J, Moehl Boatwright ML, et al.: Subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients with advanced illness: a double-blind, randomized, parallel group, dose-ranging study. J Pain Symptom Manage 35 (5): 458-68, 2008.
8. Meissner W, Leyendecker P, Mueller-Lissner S, et al.: A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation. Eur J Pain 13 (1): 56-64, 2009.

Impaction

Etiology of Impaction

Five major factors precipitate impaction:

  • Opioid analgesics.
  • Prolonged inactivity.
  • Dietary alterations.
  • Psychiatric illness.
  • Chronic use of drugs for constipation.[1]

    Laxatives used to decrease constipation are the drugs that contribute most to the development of constipation and impaction. Repeated and escalating dosing of laxatives renders the colon less sensitive to its intrinsic reflexes stimulated by distention. (Refer to the Etiology of Constipation section of this summary for causes of constipation that may lead to impaction.)

Signs and Symptoms of Impaction

The patient may exhibit symptoms similar to constipation or present with symptoms unrelated to the gastrointestinal system. If the impaction presses on the sacral nerves, the patient may experience back pain. If the impaction presses on the ureters, bladder, or urethra, urinary symptoms can develop. These symptoms include increased or decreased frequency or urgency of urination, or urinary retention.

When abdominal distention occurs, movement of the diaphragm is compromised, leading to insufficient aeration with subsequent hypoxia and left ventricular dysfunction. Hypoxia can, in turn, precipitate angina or tachycardia. If the vasovagal response is stimulated by the pressure of impaction, the patient may become dizzy and hypotensive.

Movement of stool around the impaction may result in diarrhea, which can be explosive. Coughing or activities that increase intra-abdominal pressure may cause leakage of stool. The leakage may be accompanied by nausea, vomiting, abdominal pain, and dehydration and is virtually diagnostic of the condition. Thus, the patient with an impaction may present in an acutely confused and disoriented state, with signs of tachycardia, diaphoresis, fever, elevated or low blood pressure, and/or abdominal fullness or rigidity.

Assessment of Impaction

Assessment includes the questions discussed previously for the patient with constipation (refer to the Assessment of Constipation section of this summary for the list of questions). Additional assessment includes auscultation of bowel sounds to determine if they are present, absent, hyperactive, or hypoactive. The abdomen should be inspected for distention and gently palpated for any masses, rigidity, or tenderness. A rectal examination will determine the presence of stool in the rectum or sigmoid colon. An abdominal x-ray (flat and upright) would show loss of haustral markings, gas patterns reflecting gross amounts of stool, and dilatation proximal to the impaction.[2]

If a diagnosis of fecal impaction is uncertain, a laboratory workup can rule out other problems. A complete blood cell count, appropriate blood chemistries, chest x-ray, and an electrocardiogram can be performed. If the patient has become dehydrated, the blood urea nitrogen, creatinine, and serum osmolality will be elevated. There may be an elevation of the hemoglobin and hematocrit indicating hemoconcentration. The white blood cell (WBC) count may be slightly elevated in the presence of a fever. If the WBC count is extremely elevated and the patient is exhibiting a high fever and abdominal pain, an obstruction, perforation, infection, or inflammatory process must be ruled out. With marked distention of the cecum (diameter =12 cm), there is a risk of bowel perforation.

Treatment of Impaction

The primary treatment of impaction is to hydrate and soften the stool so that it can be removed or passed. Enemas (oil retention, tap water, or hypertonic phosphate) lubricate the bowel and soften the stool. Caution must be exercised; fecal impaction can irritate the bowel wall, and enemas in excess may perforate the bowel. The patient may need to be digitally disimpacted if the stool is within reach. This is best done after administering an enema to lubricate the bowel.

Nonstimulating bowel softeners such as docusate can be used to help soften stool higher in the colon. Mineral or olive oil can be given to loosen the stool. Caution should be used when giving docusate sodium with mineral oil because there could be an increased systemic absorption of the mineral oil leading to systemic lipid granulomas.[3] Glycerin suppositories can also be used. Any laxatives that might stimulate the bowel or cause cramping should be avoided so that the bowel is not damaged further.

Current Clinical Trials

Check NCI's PDQ Cancer Clinical Trials Registry for U.S. supportive and palliative care trials about constipation, impaction, and bowel obstruction that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Cefalu CA, McKnight GT, Pike JI: Treating impaction: a practical approach to an unpleasant problem. Geriatrics 36 (5): 143-6, 1981.
2. Bruera E, Suarez-Almazor M, Velasco A, et al.: The assessment of constipation in terminal cancer patients admitted to a palliative care unit: a retrospective review. J Pain Symptom Manage 9 (8): 515-9, 1994.
3. Brandt LJ: Gastrointestinal Disorders of the Elderly. New York, NY: Raven Press, 1984.

Large or Small Bowel Obstruction

There are four types of obstruction:

1. Simple.
2. Closed-loop.
3. Strangulated.
4. Incarcerated.

A simple obstruction is blocked in one place; a closed-loop obstruction is blocked in two places. A closed-loop obstruction may develop when the bowel twists around on itself, isolating the looped section of the bowel and obstructing the portion above it. With a strangulated obstruction, there is decreased blood flow to the bowel that, if not relieved, will develop into an incarcerated obstruction, and the bowel will become necrotic.

The obstructing mechanism can be mechanical or nonmechanical. Mechanical factors can be anything that causes a narrowing of the intestinal lumen (e.g., inflammation or trauma to the bowel, neoplasms, adhesions, hernias, volvulus, or a compression from outside the intestinal tract).[1] Nonmechanical factors include those that interfere with the muscle action or innervation of the bowel: paralytic ileus, mesenteric embolus or thrombus, and hypokalemia.

Eighty percent of bowel obstructions occur in the small intestine; the other 20% occur in the colon.[2] Bowel obstructions are frequently seen in the ileum. Small bowel obstructions are caused often by adhesions or hernias, whereas large bowel obstructions are caused by carcinomas, volvulus, or diverticulitis. The presentation of obstruction will relate to whether the small or large intestine is involved.

Etiology of Bowel Obstruction

The most common malignancies that cause bowel obstruction are cancers of the colon, stomach, and ovary. Extra-abdominal cancers (such as lung and breast cancers and melanoma) can spread to the abdomen, causing bowel obstruction.[3] Patients who have had abdominal surgery or abdominal radiation are also at higher risk of developing bowel obstruction.[2] Bowel obstructions are most common during advanced stages of disease.

Assessment and Diagnosis of Bowel Obstruction

Examination of the patient will determine the presence or absence of abdominal pain, vomiting, and evidence of the passage of flatus or stool. A complete blood cell count, electrolyte panel, and urinalysis are obtained to evaluate fluid and electrolyte imbalance and/or sepsis. An elevated white blood cell count (15,000–20,000/mm3) suggests bowel necrosis. Flat and upright abdominal films as well as a barium enema may be necessary to determine where the obstruction is located. While it remains controversial, an upper gastrointestinal series is contraindicated with an acutely presenting obstruction because it can cause a partial obstruction to become complete or may further complicate a total obstruction. If the patient is exhibiting dehydration, oliguria, or shock, perforation of the bowel may have occurred, and immediate medical or surgical intervention is indicated. (Refer to the Nausea, Vomiting, Constipation, and Bowel Obstruction in Advanced Cancer section in the PDQ summary on Nausea and Vomiting for more information.)

Treatment of Acute Bowel Obstruction

Careful serial examinations are necessary in the management of patients with progressive abdominal symptoms that may be due to acute bowel obstruction. The principles of supportive care in this setting include volume resuscitation, correction of electrolyte imbalances, and transfusion support (if necessary). These measures should precede or accompany decompression efforts.

When bowel obstruction is partial, decompression of the distended bowel may be attempted with nasogastric or intestinal tubes. Although use of these tubes may be successful in reducing edema, relieving fluid and gas accumulation, or decreasing the need for multiple stage procedures,[4] surgery may be necessary within 24 hours if there is complete, acute obstruction. The use of self-expandable stents to decompress complete, acute malignant bowel obstruction has been noted to decrease the frequency of unnecessary surgery by permitting staging of the disease, increasing the rate of primary anastomosis relative to colostomy, and decreasing morbidity in patients with left-sided colon and rectal malignancies. Further study is warranted including cost analysis.[5]

Management of Chronic, Malignant Bowel Obstruction

Patients with advanced cancer may have chronic, progressive bowel obstruction that is inoperable.[6,7] The most frequent causes of inoperability are extensive tumor and multiple partial obstructions.[8,9,10] A retrospective review evaluating surgical palliation of malignant bowel obstruction secondary to peritoneal carcinomatosis in 63 patients with nongynecological cancer used the ability to tolerate solid food at hospital discharge as the criterion for successful palliation. Multiple logistic regression analysis identified the absence of ascites and obstruction not involving the small bowel as predictors of successful surgical palliation in this population. Successful palliation was achieved in 45% of patients and was maintained in 76% of this group at a median follow-up of 78 days, for an overall success rate of 35%. Postoperative mortality was 15%, and postoperative complications occurred in 44%.[11]

For some patients with malignant obstructions of the gastrointestinal tract, the use of expandable metal stents may provide palliation of obstructive symptoms. Available stents include esophageal, biliary, gastroduodenal, and colorectal.[12,13,14,15,16,5,17] Stents may be placed under endoscopic guidance, with or without fluoroscopy, or by an interventional radiologist using fluoroscopy. Morbidity with stent placement may be lower than with surgery. Adequate imaging of the stricture itself and the gastrointestinal tract distal to the stricture is recommended to assess stricture length, detect multifocal disease, and determine the appropriateness of stenting.[18,19,20].

When neither surgery nor stenting is possible, the accumulation of the unabsorbed secretions produce nausea, vomiting, pain, and colicky activity as a consequence of the partial or complete occlusion of the lumen. In this case, a gastrostomy tube is commonly used to provide decompression of air and fluid that may be accumulating and causing visceral distention and pain. The gastrostomy tube is placed into the stomach and is attached to a drainage bag that can be easily concealed under clothing. When the valve between the gastrostomy tube and the bag is open, the patient may be able to eat or drink by mouth without creating discomfort since the food is drained directly into the bag. Dietary discretion is advised to minimize the risk of tube obstruction by solid food. If the obstruction improves, the valve can be closed and the patient may once again benefit from enteral nutrition.

Sometimes, decompression is difficult even with a gastrostomy tube in place. This problem may be caused by the accumulation of fluid, since several liters per day of gastrointestinal secretions may be produced. To relieve continuous abdominal pain, opioid analgesics via continuous subcutaneous or intravenous infusion may be necessary. Effective antispasmodics in this situation include anticholinergics (such as hyoscine butylbromide) [21] and possibly corticosteroids as well as centrally acting agents. If the bowel obstruction is thought to be functional (rather than mechanical) in origin, metoclopramide is the drug of choice because of its prokinetic effects on the bowel. For complete bowel obstruction thought to be irreversible, a trial of an antispasmodic such as hyoscyamine may decrease bowel contractions and therefore yield pain relief. Another option for management of refractory pain and/or nausea is the synthetic somatostatinanalog octreotide. This agent inhibits the release of several gastrointestinal hormones and reduces gastrointestinal secretions.[22,23,24] Octreotide is usually given subcutaneously at 50 to 200 µg 3 times per day and may reduce the nausea, vomiting, and abdominal pain of malignant bowel obstruction. For selected patients, the addition of an anticholinergic such as scopolamine may be helpful in reducing the associated painful colic of malignant bowel obstruction when octreotide alone is ineffective. When either scopolamine or octreotide is used alone, each is ineffective.[12,25,26,27] Corticosteroids are widely used in treating bowel obstruction, but empirical support is limited.[28] They may be useful as adjuvant antiemetics and analgesics in this setting given as dexamethasone at a starting dose of 6 to 10 mg subcutaneously or intravenously 3 to 4 times per day.[12,25] (Refer to the Nausea, Vomiting, Constipation, and Bowel Obstruction in Advanced Cancer section in the PDQ summary on Nausea and Vomiting for more information.)

Current Clinical Trials

Check NCI's PDQ Cancer Clinical Trials Registry for U.S. supportive and palliative care trials about constipation, impaction, and bowel obstruction that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Givens BA, Simmons SJ: Gastroenterology in Clinical Nursing. 4th ed. St. Louis, Mo: C.V. Mosby Co, 1984.
2. Bouchier IA: Gastroenterology. 3rd ed. London: Balliere Tindall, 1982.
3. Ripamonti C, De Conno F, Ventafridda V, et al.: Management of bowel obstruction in advanced and terminal cancer patients. Ann Oncol 4 (1): 15-21, 1993.
4. Horiuchi A, Maeyama H, Ochi Y, et al.: Usefulness of Dennis Colorectal Tube in endoscopic decompression of acute, malignant colonic obstruction. Gastrointest Endosc 54 (2): 229-32, 2001.
5. Martinez-Santos C, Lobato RF, Fradejas JM, et al.: Self-expandable stent before elective surgery vs. emergency surgery for the treatment of malignant colorectal obstructions: comparison of primary anastomosis and morbidity rates. Dis Colon Rectum 45 (3): 401-6, 2002.
6. Ripamonti C, Bruera E: Palliative management of malignant bowel obstruction. Int J Gynecol Cancer 12 (2): 135-43, 2002 Mar-Apr.
7. Potluri V, Zhukovsky DS: Recent advances in malignant bowel obstruction: an interface of old and new. Curr Pain Headache Rep 7 (4): 270-8, 2003.
8. Jung GS, Song HY, Kang SG, et al.: Malignant gastroduodenal obstructions: treatment by means of a covered expandable metallic stent-initial experience. Radiology 216 (3): 758-63, 2000.
9. Camúñez F, Echenagusia A, Simó G, et al.: Malignant colorectal obstruction treated by means of self-expanding metallic stents: effectiveness before surgery and in palliation. Radiology 216 (2): 492-7, 2000.
10. Coco C, Cogliandolo S, Riccioni ME, et al.: Use of a self-expanding stent in the palliation of rectal cancer recurrences. A report of three cases. Surg Endosc 14 (8): 708-11, 2000.
11. Blair SL, Chu DZ, Schwarz RE: Outcome of palliative operations for malignant bowel obstruction in patients with peritoneal carcinomatosis from nongynecological cancer. Ann Surg Oncol 8 (8): 632-7, 2001.
12. Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001.
13. Law WL, Chu KW, Ho JW, et al.: Self-expanding metallic stent in the treatment of colonic obstruction caused by advanced malignancies. Dis Colon Rectum 43 (11): 1522-7, 2000.
14. Repici A, Reggio D, De Angelis C, et al.: Covered metal stents for management of inoperable malignant colorectal strictures. Gastrointest Endosc 52 (6): 735-40, 2000.
15. Harris GJ, Senagore AJ, Lavery IC, et al.: The management of neoplastic colorectal obstruction with colonic endolumenal stenting devices. Am J Surg 181 (6): 499-506, 2001.
16. Aviv RI, Shyamalan G, Watkinson A, et al.: Radiological palliation of malignant colonic obstruction. Clin Radiol 57 (5): 347-51, 2002.
17. Dauphine CE, Tan P, Beart RW Jr, et al.: Placement of self-expanding metal stents for acute malignant large-bowel obstruction: a collective review. Ann Surg Oncol 9 (6): 574-9, 2002.
18. Lopera JE, Alvarez O, Castaño R, et al.: Initial experience with Song's covered duodenal stent in the treatment of malignant gastroduodenal obstruction. J Vasc Interv Radiol 12 (11): 1297-303, 2001.
19. Razzaq R, Laasch HU, England R, et al.: Expandable metal stents for the palliation of malignant gastroduodenal obstruction. Cardiovasc Intervent Radiol 24 (5): 313-8, 2001 Sep-Oct.
20. Baron TH, Rey JF, Spinelli P: Expandable metal stent placement for malignant colorectal obstruction. Endoscopy 34 (10): 823-30, 2002.
21. De Conno F, Caraceni A, Zecca E, et al.: Continuous subcutaneous infusion of hyoscine butylbromide reduces secretions in patients with gastrointestinal obstruction. J Pain Symptom Manage 6 (8): 484-6, 1991.
22. Ripamonti C, Mercadante S, Groff L, et al.: Role of octreotide, scopolamine butylbromide, and hydration in symptom control of patients with inoperable bowel obstruction and nasogastric tubes: a prospective randomized trial. J Pain Symptom Manage 19 (1): 23-34, 2000.
23. Fallon MT: The physiology of somatostatin and its synthetic analogue, octreotide. European Journal of Palliative Care 1 (1): 20-2, 1994.
24. Mystakidou K, Tsilika E, Kalaidopoulou O, et al.: Comparison of octreotide administration vs conservative treatment in the management of inoperable bowel obstruction in patients with far advanced cancer: a randomized, double- blind, controlled clinical trial. Anticancer Res 22 (2B): 1187-92, 2002 Mar-Apr.
25. Mercadante S: Assessment and management of mechanical bowel obstruction. In: Portenoy RK, Bruera E, eds.: Topics in Palliative Care. Volume 1. New York, NY: Oxford University Press, 1997, pp. 113-30.
26. Fainsinger RL: Integrating medical and surgical treatments in gastrointestinal, genitourinary, and biliary obstruction in patients with cancer. Hematol Oncol Clin North Am 10 (1): 173-88, 1996.
27. Ripamonti C, Panzeri C, Groff L, et al.: The role of somatostatin and octreotide in bowel obstruction: pre-clinical and clinical results. Tumori 87 (1): 1-9, 2001 Jan-Feb.
28. Feuer DJ, Broadley KE: Systematic review and meta-analysis of corticosteroids for the resolution of malignant bowel obstruction in advanced gynaecological and gastrointestinal cancers. Systematic Review Steering Committee. Ann Oncol 10 (9): 1035-41, 1999.

Diarrhea

The reported prevalence and severity of diarrhea vary greatly. Some chemotherapeutic regimens are associated with diarrhea rates as high as 50% to 80%, particularly those containing fluoropyrimidines or irinotecan.[1,2] Diarrhea is also commonly observed in patients diagnosed with carcinoid tumors, receiving radiation therapy to abdominal/pelvic fields, or undergoing bone marrow transplantation or surgical intervention of the gastrointestinal tract.[3] In a large heterogeneous sample of cancer patients in various stages of treatment, the prevalence of moderate-to-severe diarrhea was 14%.[4] Diarrhea occurs in approximately 7% to 10% of cancer patients upon admission to hospice.[5] Among children with cancer during the last month of life, 19% experienced diarrhea.[6]

The consequences of diarrhea can be significant and life-threatening. According to the National Cancer Institute's (NCI's) Common Toxicity Criteria, more than half of patients receiving chemotherapy for colorectal cancer experienced diarrhea of grade 3 (severe) or grade 4 (life-threatening), requiring treatment changes or the reduction, delay, or discontinuation of therapy (see Table 1).[7,8] A review of several clinical trials of irinotecan plus high-dose fluorouracil and leucovorin in colorectal cancer revealed early death rates of 2.2% to 4.8%, primarily due to gastrointestinal toxicity.[9] With the advent of more aggressive anticancer therapies, the potential physical and psychosocial consequences of diarrhea and its indirect effect on cancer treatment outcome are likely to expand.[10]

Table 1. National Cancer Institute's Common Toxicity Criteria for Grading Severity of Diarrhea

BMT = bone marrow transplant.
Toxicity 0 1 2 3 4
Patients without a colostomy None Increase of <4 stools/day over pretreatment Increase of 4–6 stools/day or nocturnal stools Increase of =7 stools/day >10 stools/day
None None Moderate cramping, not interfering with normal activity Severe cramping and incontinence, interfering with daily activities Grossly bloody diarrhea and need for parenteral support
Patients with a colostomy None Mild increase in loose, watery colostomy output compared with pretreatment Moderate increase in loose, watery colostomy output compared with pretreatment, but not interfering with normal activity Severe increase in loose, watery colostomy output compared with pretreatment, interfering with normal activity Physiological consequences requiring intensive care; hemodynamic collapse
For patients undergoing BMT None >500 mL to =1,000 mL of diarrhea/day >1,000 mL to =1,500 mL of diarrhea/day >1,500 mL of diarrhea/day Severe abdominal pain with or without ileus
For children undergoing BMT None >5 mL/kg to =10 mL/kg of diarrhea/day >10 mL/kg to =15 mL/kg of diarrhea/day >15 mL/kg of diarrhea/day Severe abdominal pain with or without ileus

Etiology of Diarrhea

In patients being treated for cancer, diarrhea is most commonly induced by therapy.[11] Conventional methods of diarrhea-causing treatment include surgery, chemotherapy, radiation therapy, and bone marrow transplantation. Other causes of acute diarrhea include antibiotic therapy, stress and anxiety associated with cancer diagnosis and treatment, and infection.[12] Typical infections are of viral, bacterial, protozoan, parasitic, or fungal etiology; they may also be caused by pseudomembranous colitis, a cause of diarrhea that often does not respond to treatment.[3]Clostridium difficile is a common cause of pseudomembranous colitis. Other causes of diarrhea in patients with cancer include the underlying cancer, responses to diet, or concomitant diseases (see Table 2). Common causes of diarrhea in patients receiving palliative care are difficulty adjusting the laxative regimen and impaction leading to leakage of stool around the fecal obstruction.

Another strategy for categorizing the causes of diarrhea is by putative underlying mechanisms. These include exudative (i.e., excess blood or mucous enters the gastrointestinal tract), malabsorptive, dysmotile, osmotic, and secretory (due to increased secretion of electrolytes and fluid—probably the mechanism underlying chemotherapy-induced diarrhea), or combinations of these factors.[13]

Surgery, a primary treatment modality for many cancers, can affect the body by mechanical, functional, and physiological alterations. Postsurgical complications of gastrointestinal surgery affecting normal bowel function that may contribute to diarrhea include increased transit time, gastroparesis, fat malabsorption, lactose intolerance, fluid and electrolyte imbalance, and dumping syndrome.[14,15]

Certain chemotherapeutic agents can alter normal absorption and secretion functions of the small bowel, resulting in treatment-related diarrhea.[7] Examples of chemotherapy agents with diarrhea-related potential are listed in Table 2 below. Patients receiving concomitant abdominal or pelvic radiation therapy or recovering from recent gastrointestinal surgery will often experience more severe diarrhea.

Radiation therapy to abdominal, pelvic, lumbar, or para-aortic fields can result in changes to normal bowel function. Factors contributing to the occurrence and severity of intestinal complications depend on total dose, fractionation, volume of bowel irradiated, and concomitant chemotherapy. Common side effects of intestinal enteritis include diarrhea, malabsorption, gas, bloating, and cramping. Acute intestinal side effects occur at approximately 10 Gy and may last up to 8 to 12 weeks posttherapy. Chronic radiation enteritis may present months to years after completion of therapy and necessitates dietary modification and pharmacological management and, in some instances, surgical intervention (see the section on Radiation Enteritis in this summary).

Graft-versus-host disease (GVHD) is a major complication of allogeneic transplantation, and the intestinal tract, skin, and liver are commonly affected. Symptoms of gastrointestinal GVHD include nausea and vomiting, severe abdominal pain and cramping, and watery, green diarrhea.[16] The volume of accompanying GVHD-associated diarrhea may reach up to 10 L per day and is an indicator of the degree and extent of mucosal damage.[17] Acute GVHD is usually manifested within 100 days posttransplant, although it can occur as early as 7 to 10 days posttransplant. It may resolve or develop into a chronic form requiring long-term treatment and dietary management.

Table 2. Possible Contributions to Diarrhea in Cancer

Cancer-related [5,18] Carcinoid syndrome
Colon cancer
Lymphoma
Medullary carcinoma of the thyroid
Pancreatic cancer, particularly islet cell tumors (Zollinger-Ellison syndrome)
Pheochromocytoma
Surgery- or procedure-related [14] Celiac plexus block
Cholecystectomy, esophagogastrectomy
Gastrectomy, pancreaticoduodenectomy (Whipple procedure)
Intestinal resection (malabsorption due to short bowel syndrome)
Vagotomy
Chemotherapy-related [19,20,21] Capecitabine, cisplatin, cytosine arabinoside, cyclophosphamide, daunorubicin, docetaxel, doxorubicin, 5-fluorouracil, interferon, irinotecan, leucovorin, methotrexate, oxaliplatin, paclitaxel, topotecan, lapatinib
Radiation therapy–related (refer to the Radiation Enteritis section of this summary) [22,23] Irradiation to the abdomen, para-aortics, lumbar, and pelvis
Bone marrow transplantation–related [24] Conditioning chemotherapy, total-body irradiation, graft-versus-host disease after allogeneic bone marrow or peripheral blood stem cell transplants
Drug adverse effects [5,18] Antibiotics, magnesium-containing antacids, antihypertensives, colchicine, digoxin, iron, lactulose, laxatives, methyldopa, metoclopramide, misoprostol, potassium supplements, propanolol, theophylline
Concurrent disease [5,18] Diabetes, hyperthyroidism, inflammatory bowel disease (Crohn disease, diverticulitis, gastroenteritis, HIV/AIDS, ulcerative colitis), obstruction (tumor-related)
Infection [25] Clostridium difficile, Clostridium perfringens, Bacillus cereus, Giardia lamblia, Cryptosporidium, Salmonella, Shigella, Campylobacter, Rotavirus
Fecal impaction [5,18] Constipation leading to obstruction
Diet [5,18] Alcohol, milk, and dairy products (particularly in patients with lactose intolerance)
Caffeine-containing products (coffee, tea, chocolate), specific fruit juices (prune juice, unfiltered apple juice, sauerkraut juice)
High-fiber foods (raw fruits and vegetables, nuts, seeds, whole-grain products, dried legumes); high-fat foods (deep fat–fried foods, high-fat containing foods)
Lactulose intolerance or food allergies
Sorbitol-containing foods (candy and chewing gum); hot and spicy foods; gas-forming foods and beverages (cruciferous vegetables, dried legumes, melons, carbonated beverages)
Psychological factors [18] Stress

Assessment

Because of the potentially life-threatening nature of diarrhea, rapid, yet thorough, assessment is imperative. Few standardized assessment tools are available, and studies suggest that, as a result, standardized assessment is rare in the clinical setting.[3] For a complete assessment, one author suggests obtaining background information from the patient that includes the type and extent of the patient's cancer, anticancer treatment, comorbid factors, coexisting symptoms, patient and provider perceptions, as well as a thorough description of the diarrhea. Stringent monitoring conducted at least weekly is indicated during therapy using chemotherapeutic agents known to cause diarrhea.[9] The NCI's Common Toxicity Criteria (Table 1) evaluate diarrhea by number of stools per day, need for parenteral support, nocturnal stools, incontinence, and hemodynamic collapse.[8]

The history also should include questions regarding the frequency of bowel movements during the past 24 hours, the character of the fecal material, and the time course of the development of diarrhea.[26] One author has developed a visual tool to assist patients and families in characterizing the consistency of the stool.[27] Six diagrams illustrate fecal material consistency ranging from well-formed, formed, and semiformed to loose, very loose, and liquid. Patients should be questioned regarding related symptoms that might indicate hemodynamic compromise or the underlying etiology. Specifically, questions should include information about dizziness, orthostatic symptoms, lethargy, cramping, abdominal pain, nausea, vomiting, fever, and rectal bleeding. These symptoms should be classified as complicated or uncomplicated, with therapy based on these classifications.[28] Uncomplicated symptoms include grade 1 or 2 diarrhea with no other signs or symptoms. Management is conservative. Complicated symptoms include grade 1 or 2 diarrhea with any one of the following risk factors: moderate to severe cramping, grade 2 or higher nausea/vomiting (see Table 3 below), decreased performance status, fever, sepsis, neutropenia, frank bleeding, or dehydration. Grade 3 or 4 diarrhea is also classified as complicated. Thorough evaluation and close monitoring is warranted.[28] The time course of diarrhea and concomitant symptom development are key to determining underlying etiology.[26] Medication and dietary intake, as well as a history of recent travel, may provide additional clues regarding etiology. Weight loss and reduced urine output provide additional data regarding the severity of the effects of diarrhea.

Table 3. Criteria for Grading Severity of Nausea and Vomitinga

a Adapted from Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, Version 3.0, DCTD, NCI, NIH, DHHS.
  Grade 1 Grade 2 Grade 3 Grade 4 Grade 5
Nausea Loss of appetite without alteration in eating habits Oral intake decreased without significant weight loss, dehydration or malnutrition; IV fluids indicated <24 h Inadequate oral caloric or fluid intake; IV fluids, tube feedings, or TPN indicated =24 h Life-threatening consequences Death
Vomiting 1 episode in 24 h 2–5 episodes in 24 h; IV fluids indicated <24 h =6 episodes in 24 h; IV fluids, or TPN indicated =24 h Life-threatening consequences Death

The goal of physical examination is to identify potential causes of diarrhea and its complications as quickly as possible to reduce morbidity. The physical examination should include vital signs and evaluation of skin turgor and oral mucosa to assess hemodynamic status and dehydration. Abdominal examination includes evaluation for rebound tenderness, guarding, hypoactive or hyperactive bowel sounds, and stool collection. A rectal exam can rule out fecal impaction but should be performed judiciously in neutropenic or thrombocytopenic patients.[5]

Laboratory tests may include stool cultures for bacterial, fungal, and viral pathogens. A complete chemistry panel and hematologic profile can provide information regarding the effect of diarrhea on kidney function and electrolytes as well as identify changes in white blood cell count in response to infection. Urinalysis with specific gravity can provide information regarding hydration status. Stool osmolality may also be measured.[5]

In some cases, radiographic procedures are conducted to identify ileus, obstruction, or other abnormalities. In rare cases, endoscopy may be indicated.

Management

A review of early toxic deaths in two NCI-sponsored cooperative trials of irinotecan plus high-dose fluorouracil and leucovorin for advanced colorectal cancer has led to the revision of previously published clinical practice guidelines for the treatment of cancer treatment–induced diarrhea, with a heightened emphasis on assessment and early aggressive interventions. The guidelines distinguish between uncomplicated and complicated diarrhea.[28]

Uncomplicated symptoms

The current treatment of cancer-related diarrhea is often empiric and nonspecific. Whenever possible, treat underlying causes such as fecal impaction or modify the stimulant laxative regimen as necessary. Medications such as bulk laxatives and promotility agents (e.g., metoclopramide) should be discontinued. Dietary modifications are commonly implemented to stop or lessen the severity of cancer treatment-related diarrhea.[7,23,24,29] One author recommends that patients should consume foods that build stool consistency, are low in fiber, contain minerals, and do not stimulate or irritate the gastrointestinal tract.[20] In some cases, dietary modification for diarrhea management includes advising patients to eat small, frequent meals and avoid lactose-containing food (milk and dairy products), spicy foods, alcohol, caffeine-containing foods and beverages, certain fruit juices, gas-forming foods and beverages, high-fiber foods, and high-fat foods.[30] For mild cases of diarrhea, the BRAT (bananas, rice, apples, toast) diet may reduce the frequency of stools. When experiencing diarrhea, patients should be encouraged to increase clear liquid intake to at least 3 L per day (e.g., water, sports drinks, broth, weak decaffeinated teas, caffeine-free soft drinks, clear juices, and gelatin).[31,12] (Refer to the Diarrhea subsection of the Nutritional Suggestions for Symptom Management section in the PDQ summary on Nutrition in Cancer Care for more information.)

Probiotics are nutritional supplements that contain a defined amount of viable microorganisms and, upon administration, confer a benefit to the patient.[32] The use of probiotic functional foods (beneficial live microorganisms) to modify gut microflora has been suggested in clinical conditions associated with diarrhea, gut-barrier dysfunction, and inflammatory response.[33] There are a vast number of different strains of probiotics; however, much of the clinical research has investigated the species belonging to the family of Lactobacillus and Bifidobacterium. Probiotics have been promoted for the following:[34,35,36,37,38,39]

  • Prevention of antibiotic-induced diarrhea and rotavirus.
  • Treatment or prevention of inflammatory bowel disease, irritable bowel syndrome, and gastroenteritis.
  • Treatment of necrotizing enterocolitis in premature infants.

The results of one study among adults with cancer have been published. In a double-blind, randomized, controlled trial, 450 adults with cancer who were receiving radiation to the pelvic region were randomly assigned to receive the blend probiotic product VSL #3 or placebo during radiation therapy. The authors reported a decrease in the incidence and severity of diarrhea. No adverse events were reported.[40]

Clinical trials for the following patients are under way:

  • Patients with familial adenomatous polyposis (NCT00319007).
  • Adults undergoing allogeneic hematopoietic stem cell transplantation (CINJ-060802).
  • Children and adolescents undergoing allogeneic myeloablative hematopoietic stem cell transplantation (NCT01010867).

While some case reports suggest the efficacy of glutamine in relieving diarrhea and other gastrointestinal symptoms associated with cancer therapy, one randomized controlled trial using oral glutamine to prevent pelvic radiation-induced diarrhea was unable to demonstrate any benefit.[41,42,43]

The goals of pharmacologic therapy include inhibition of intestinal motility, reduction in intestinal secretions, and promotion of absorption. Absorbents include agents that form a gelatinous mass that gives density to fecal material. Methylcellulose and pectin are most commonly used, with little data to support their efficacy. These bulk-forming agents may not be well tolerated in some patients because of the large volume required for therapeutic effect and the associated abdominal discomfort and bloating. Adsorbents such as kaolin, clays, and activated charcoals have been used extensively, but no data support their use. Furthermore, they may inhibit absorption of other oral antidiarrheals that may be administered.

Opioids bind to receptors within the gastrointestinal tract and reduce diarrhea by reducing transit time. Loperamide is the most common opioid used, due to its availability and reduced effect on cognition, although codeine and other opioids can also be effective.[18] Common loperamide doses begin with 4 mg, followed by 2 mg after each unformed stool with a maximum of approximately 12 mg/day.[26,5] Regardless of the dose, however, loperamide may be less effective in patients with grade 3 or 4 diarrhea.[44]

Mucosal prostaglandin inhibitors, also referred to as antisecretory agents, include aspirin, bismuth subsalicylate, corticosteroids, and octreotide. Aspirin may be useful for radiation-induced diarrhea. Bismuth subsalicylate is believed to have direct antimicrobial effects on Escherichia coli, hence its prophylactic use in traveler's diarrhea. This agent is contraindicated in patients who should not be taking aspirin, and large doses can produce toxic salicylate levels. Corticosteroids reduce edema associated with obstruction and radiation colitis and can reduce hormonal influences of some endocrine tumors.

Other pharmacologic therapies for the relief of diarrhea may be specific to the underlying mechanism. Delayed diarrhea (>24 hours) occurs with irinotecan and can be severe in 25% of patients.[45] In a small study of seven patients, six patients obtained relief with oral neomycin, 1,000 mg 3 times daily. This relief occurred without reduction in the active metabolite of irinotecan, SN-38; thus, the poorly metabolized antibiotic did not alter efficacy of the chemotherapeutic agent.[46] In another small study of 37 patients with non-small cell lung cancer receiving irinotecan, investigators alkalized the feces through oral administration of sodium bicarbonate, basic water, and ursodeoxycholic acid, while speeding transit time of the drug metabolites (thought to reduce damage to the intestinal lumen by reducing stasis of the drug) through the use of magnesium oxide. The incidence of delayed diarrhea was significantly reduced in this group when compared to 32 patients receiving the same chemotherapeutic regimen without oral alkalization and controlled defecation.[47]

In addition to antidiarrheal agents and immunosuppressive medications, a specialized five-phase dietary regimen should be instituted to effectively manage the diarrhea associated with GVHD.[24] Phase 1 consists of total bowel rest until the diarrhea is reduced. Nitrogen losses associated with diarrhea can be severe and are compounded by the high-dose corticosteroids used to treat GVHD. Phase 2 reintroduces oral feedings consisting of beverages that are isotonic, low-residue, and lactose-free to compensate for the loss of intestinal enzymes secondary to alterations in the intestinal villi and mucosa. If these beverages are well tolerated, phase 3 may reintroduce solids containing minimal lactose, low fiber, low fat, low total acidity, and no gastric irritants. In phase 4, dietary restrictions are progressively reduced as foods are gradually reintroduced and tolerance is established. Phase 5 includes the resumption of the patient's regular diet; however, most patients usually remain lactose intolerant.

Complicated symptoms

While the optimal dose of octreotide has not been determined, a panel of experts has recommended that complicated cases of diarrhea should be managed with IV fluids, octreotide at a starting dose of 100 to 150 µg subcutaneously (SC) 3 times a day or 25 to 50 µg/hour IV with a dose escalation to 500 µg 3 times a day, and administration of antibiotics. This regimen should be continued until the patient has been diarrhea free for 24 hours.[28] Particularly when patients are receiving chemotherapy, additional evaluation should include stool workup (including blood, fecal leukocytes, C. difficile, Salmonella, Escherichia coli, Campylobacter, and infectious colitis), complete blood count, and electrolyte profile.[28] This workup and treatment should also be considered for patients who progress to grade 3 or 4 diarrhea while taking loperamide. The same panel suggests that severe radiation therapy–induced diarrhea may not require hospitalization (an alternative outpatient unit or intensive home care nursing may be able to provide the same level of care and monitoring) but the patient's constellation of symptoms should be considered to determine the appropriate workup and whether IV fluids or octreotide is indicated.

Octreotide, a somatostatin analog, is currently the most promising agent in the management of severe diarrhea caused by a variety of diseases and treatments. The doses used in clinical trials have varied widely. Regardless of the lack of consensus regarding optimal dose, octreotide has been shown to be effective in relieving diarrhea associated with AIDS, carcinoid syndrome, and vasoactive intestinal polypeptide tumors.[48,18] Several open-label and randomized controlled studies of octreotide in the relief of chemotherapy-induced diarrhea have demonstrated the efficacy of this therapy.[49,50,51,52,53,54] In a prospective trial of 32 patients who had chemotherapy-induced diarrhea that was refractory to loperamide, 100 µg SC 3 times a day produced complete resolution in 30 patients. Resolution occurred rapidly, with 5 patients responding within 24 hours, 14 patients responding within 48 hours, and 11 patients responding within 72 hours after beginning treatment. No adverse effects of the octreotide were noted.[55] Octreotide has also been shown to be effective in diarrhea associated with GVHD.[56,57] An expert panel recommended using high-dose loperamide (2 mg every 2 hours) for the first day of chemotherapy-induced diarrhea that is low grade (1 and 2), followed by octreotide, 100 to 150 µg every 8 hours.[26] If the patient presents with severe diarrhea (grade 3 or 4), octreotide, 500 to 1,500 µg SC or IV every 8 hours, should be first-line therapy. A phase III, double-blind study of depot octreotide for the prevention of diarrhea during pelvic radiation treatment did not demonstrate any benefit.[58] In fact, some gastrointestinal symptoms such as cramping may have been worse. Parenteral hydration and electrolyte supplementation may be indicated, and in severe cases, total parenteral nutrition may be initiated. (Refer to the PDQ summary on Nutrition in Cancer Care for further information.)

Current Clinical Trials

Check NCI's PDQ Cancer Clinical Trials Registry for U.S. supportive and palliative care trials about diarrhea that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Leichman CG, Fleming TR, Muggia FM, et al.: Phase II study of fluorouracil and its modulation in advanced colorectal cancer: a Southwest Oncology Group study. J Clin Oncol 13 (6): 1303-11, 1995.
2. Rothenberg ML, Eckardt JR, Kuhn JG, et al.: Phase II trial of irinotecan in patients with progressive or rapidly recurrent colorectal cancer. J Clin Oncol 14 (4): 1128-35, 1996.
3. Rutledge DN, Engelking C: Cancer-related diarrhea: selected findings of a national survey of oncology nurse experiences. Oncol Nurs Forum 25 (5): 861-73, 1998.
4. Cleeland CS, Mendoza TR, Wang XS, et al.: Assessing symptom distress in cancer patients: the M.D. Anderson Symptom Inventory. Cancer 89 (7): 1634-46, 2000.
5. Sykes NP: Constipation and diarrhoea. In: Doyle D, Hanks GW, MacDonald N, eds.: Oxford Textbook of Palliative Medicine. 2nd ed. New York, NY: Oxford University Press, 1998, pp 513-26.
6. Wolfe J, Grier HE, Klar N, et al.: Symptoms and suffering at the end of life in children with cancer. N Engl J Med 342 (5): 326-33, 2000.
7. Arbuckle RB, Huber SL, Zacker C: The consequences of diarrhea occurring during chemotherapy for colorectal cancer: a retrospective study. Oncologist 5 (3): 250-9, 2000.
8. National Cancer Institute.: Common Toxicity Criteria Manual. Bethesda, Md: National Cancer Institute, 1999. Also available online. Last accessed January 13, 2010.
9. Rothenberg ML, Meropol NJ, Poplin EA, et al.: Mortality associated with irinotecan plus bolus fluorouracil/leucovorin: summary findings of an independent panel. J Clin Oncol 19 (18): 3801-7, 2001.
10. Arnold RJ, Gabrail N, Raut M, et al.: Clinical implications of chemotherapy-induced diarrhea in patients with cancer. J Support Oncol 3 (3): 227-32, 2005 May-Jun.
11. Cartoni C, Dragoni F, Micozzi A, et al.: Neutropenic enterocolitis in patients with acute leukemia: prognostic significance of bowel wall thickening detected by ultrasonography. J Clin Oncol 19 (3): 756-61, 2001.
12. Tuchmann L, Engelking C: Cancer-related diarrhea. In: Gates RA, Fink RM, eds.: Oncology Nursing Secrets. 2nd ed. Philadelphia, Pa: Hanley and Belfus, 2001, pp 310-22.
13. Bruckstein AH: Acute diarrhea. Am Fam Physician 38 (4): 217-28, 1988.
14. Yahanda AM: Hepatobiliary cancers. In: Berger DH, Feig BW, Fuhrman GM, eds.: The M.D. Anderson Surgical Oncology Handbook. Boston, Mass: Little, Brown, 1995, pp 194-224.
15. Grant JP, Chapman G, Russell MK: Malabsorption associated with surgical procedures and its treatment. Nutr Clin Pract 11 (2): 43-52, 1996.
16. McDonald GB, Shulman HM, Sullivan KM, et al.: Intestinal and hepatic complications of human bone marrow transplantation. Part I. Gastroenterology 90 (2): 460-77, 1986.
17. Herrmann VM, Petruska PJ: Nutrition support in bone marrow transplant recipients. Nutr Clin Pract 8 (1): 19-27, 1993.
18. Mercadante S: Diarrhea in terminally ill patients: pathophysiology and treatment. J Pain Symptom Manage 10 (4): 298-309, 1995.
19. Gupta E, Lestingi TM, Mick R, et al.: Metabolic fate of irinotecan in humans: correlation of glucuronidation with diarrhea. Cancer Res 54 (14): 3723-5, 1994.
20. Wadler S, Benson AB 3rd, Engelking C, et al.: Recommended guidelines for the treatment of chemotherapy-induced diarrhea. J Clin Oncol 16 (9): 3169-78, 1998.
21. Crown JP, Burris HA 3rd, Boyle F, et al.: Pooled analysis of diarrhea events in patients with cancer treated with lapatinib. Breast Cancer Res Treat 112 (2): 317-25, 2008.
22. Makrauer FL, Oates E, Becker J, et al.: Does local irradiation affect gastric emptying in humans? Am J Med Sci 317 (1): 33-7, 1999.
23. Donaldson SS: Nutritional consequences of radiotherapy. Cancer Res 37 (7 Pt 2): 2407-13, 1977.
24. Charuhas PM: Medical nutrition therapy in bone marrow transplantation. In: McCallum PD, Polisena CG, eds.: The Clinical Guide to Oncology Nutrition. Chicago, Ill: The American Dietetic Association, 2000, pp 90-8.
25. DuPont HL: Guidelines on acute infectious diarrhea in adults. The Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol 92 (11): 1962-75, 1997.
26. Kornblau S, Benson AB, Catalano R, et al.: Management of cancer treatment-related diarrhea. Issues and therapeutic strategies. J Pain Symptom Manage 19 (2): 118-29, 2000.
27. Mertz HR, Beck CK, Dixon W, et al.: Validation of a new measure of diarrhea. Dig Dis Sci 40 (9): 1873-82, 1995.
28. Benson AB 3rd, Ajani JA, Catalano RB, et al.: Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol 22 (14): 2918-26, 2004.
29. Polisena CG: Nutrition concerns with the radiation therapy patient. In: McCallum PD, Polisena CG, eds.: The Clinical Guide to Oncology Nutrition. Chicago, Ill: The American Dietetic Association, 2000, pp 70-8.
30. McCallum PD, Polisena CG, eds.: The Clinical Guide to Oncology Nutrition. Chicago, Ill: The American Dietetic Association, 2000.
31. Hogan CM: The nurse's role in diarrhea management. Oncol Nurs Forum 25 (5): 879-86, 1998.
32. de Vrese M, Schrezenmeir J: Probiotics, prebiotics, and synbiotics. Adv Biochem Eng Biotechnol 111: 1-66, 2008.
33. Isolauri E: Probiotics in human disease. Am J Clin Nutr 73 (6): 1142S-1146S, 2001.
34. Johnston BC, Supina AL, Ospina M, et al.: Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev (2): CD004827, 2007.
35. Pillai A, Nelson R: Probiotics for treatment of Clostridium difficile-associated colitis in adults. Cochrane Database Syst Rev (1): CD004611, 2008.
36. Huertas-Ceballos A, Logan S, Bennett C, et al.: Dietary interventions for recurrent abdominal pain (RAP) and irritable bowel syndrome (IBS) in childhood. Cochrane Database Syst Rev (1): CD003019, 2008.
37. Alfaleh K, Bassler D: Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev (1): CD005496, 2008.
38. Karimi O, Peña AS: Indications and challenges of probiotics, prebiotics, and synbiotics in the management of arthralgias and spondyloarthropathies in inflammatory bowel disease. J Clin Gastroenterol 42 (Suppl 3 Pt 1): S136-41, 2008.
39. Butterworth AD, Thomas AG, Akobeng AK: Probiotics for induction of remission in Crohn's disease. Cochrane Database Syst Rev (3): CD006634, 2008.
40. Delia P, Sansotta G, Donato V, et al.: Use of probiotics for prevention of radiation-induced diarrhea. World J Gastroenterol 13 (6): 912-5, 2007.
41. Kozelsky TF, Meyers GE, Sloan JA, et al.: Phase III double-blind study of glutamine versus placebo for the prevention of acute diarrhea in patients receiving pelvic radiation therapy. J Clin Oncol 21 (9): 1669-74, 2003.
42. Savy GK: Glutamine supplementation. Heal the gut, help the patient. J Infus Nurs 25 (1): 65-9, 2002 Jan-Feb.
43. Ziegler TR, Bye RL, Persinger RL, et al.: Effects of glutamine supplementation on circulating lymphocytes after bone marrow transplantation: a pilot study. Am J Med Sci 315 (1): 4-10, 1998.
44. Cascinu S, Bichisao E, Amadori D, et al.: High-dose loperamide in the treatment of 5-fluorouracil-induced diarrhea in colorectal cancer patients. Support Care Cancer 8 (1): 65-7, 2000.
45. Creemers GJ, Lund B, Verweij J: Topoisomerase I inhibitors: topotecan and irenotecan. Cancer Treat Rev 20 (1): 73-96, 1994.
46. Kehrer DF, Sparreboom A, Verweij J, et al.: Modulation of irinotecan-induced diarrhea by cotreatment with neomycin in cancer patients. Clin Cancer Res 7 (5): 1136-41, 2001.
47. Takeda Y, Kobayashi K, Akiyama Y, et al.: Prevention of irinotecan (CPT-11)-induced diarrhea by oral alkalization combined with control of defecation in cancer patients. Int J Cancer 92 (2): 269-75, 2001.
48. Cello JP, Grendell JH, Basuk P, et al.: Effect of octreotide on refractory AIDS-associated diarrhea. A prospective, multicenter clinical trial. Ann Intern Med 115 (9): 705-10, 1991.
49. Cascinu S, Fedeli A, Fedeli SL, et al.: Control of chemotherapy-induced diarrhoea with octreotide in patients receiving 5-fluorouracil. Eur J Cancer 28 (2-3): 482-3, 1992.
50. Cascinu S, Fedeli A, Fedeli SL, et al.: Octreotide versus loperamide in the treatment of fluorouracil-induced diarrhea: a randomized trial. J Clin Oncol 11 (1): 148-51, 1993.
51. Cascinu S, Fedeli A, Fedeli SL, et al.: Control of chemotherapy-induced diarrhea with octreotide. A randomized trial with placebo in patients receiving cisplatin. Oncology 51 (1): 70-3, 1994 Jan-Feb.
52. Gebbia V, Carreca I, Testa A, et al.: Subcutaneous octreotide versus oral loperamide in the treatment of diarrhea following chemotherapy. Anticancer Drugs 4 (4): 443-5, 1993.
53. Petrelli NJ, Rodriguez-Bigas M, Rustum Y, et al.: Bowel rest, intravenous hydration, and continuous high-dose infusion of octreotide acetate for the treatment of chemotherapy-induced diarrhea in patients with colorectal carcinoma. Cancer 72 (5): 1543-6, 1993.
54. Wadler S, Haynes H, Wiernik PH: Phase I trial of the somatostatin analog octreotide acetate in the treatment of fluoropyrimidine-induced diarrhea. J Clin Oncol 13 (1): 222-6, 1995.
55. Zidan J, Haim N, Beny A, et al.: Octreotide in the treatment of severe chemotherapy-induced diarrhea. Ann Oncol 12 (2): 227-9, 2001.
56. Ippoliti C, Champlin R, Bugazia N, et al.: Use of octreotide in the symptomatic management of diarrhea induced by graft-versus-host disease in patients with hematologic malignancies. J Clin Oncol 15 (11): 3350-4, 1997.
57. Morton AJ, Durrant ST: Efficacy of octreotide in controlling refractory diarrhea following bone marrow transplantation. Clin Transplant 9 (3 Pt 1): 205-8, 1995.
58. Martenson JA, Halyard MY, Sloan JA, et al.: Phase III, double-blind study of depot octreotide versus placebo in the prevention of acute diarrhea in patients receiving pelvic radiation therapy: results of North Central Cancer Treatment Group N00CA. J Clin Oncol 26 (32): 5248-53, 2008.

Radiation Enteritis

Etiology

Almost all patients undergoing radiation to the abdomen, pelvis, or rectum will show signs of acute enteritis. Injuries clinically evident during the first course of radiation and up to 8 weeks later are considered acute.[1] Chronic radiation enteritis may present months to years after the completion of therapy, or it may begin as acute enteritis and persist after the cessation of treatment. Only 5% to 15% of persons treated with radiation to the abdomen will develop chronic problems.[2]

Factors that influence the occurrence and severity of radiation enteritis include the following:

1. Dose and fractionation.
2. Tumor size and extent.
3. Volume of normal bowel treated.
4. Concomitant chemotherapy.
5. Radiation intracavitary implants.
6. Individual patient variables (e.g., previous abdominal or pelvic surgery, hypertension, diabetes mellitus, pelvic inflammatory disease, inadequate nutrition).[3,4]

In general, the higher the daily and total dose delivered to the normal bowel and the greater the volume of normal bowel treated, the greater the risk of radiation enteritis. In addition, the individual patient variables listed above can decrease vascular flow to the bowel wall and impair bowel motility, increasing the chance of radiation injury.

Acute Radiation Enteritis

Diagnosis

Radiation therapy exerts a cytotoxic effect mainly on rapidly proliferating epithelial cells, like those lining the large and small bowel. Crypt cell wall necrosis can be observed 12 to 24 hours after a daily dose of 1.5 to 3 Gy. Progressive loss of cells, villous atrophy, and cystic crypt dilation occur in the ensuing days and weeks. Patients suffering from acute enteritis may complain of nausea, vomiting, abdominal cramping, tenesmus, and watery diarrhea. With diarrhea, the digestive and absorptive functions of the gastrointestinal (GI) tract are altered or lost, resulting in malabsorption of fat, lactose, bile salts, and vitamin B12. Symptoms of proctitis—including mucoid rectal discharge, rectal pain, and rectal bleeding (if mucosal ulceration is present)—may result from radiation damage to the anus or rectum.

Acute enteritis symptoms usually resolve 2 to 3 weeks after the completion of treatment, and the mucosa may appear nearly normal.[5]

Assessment

Patient examination and assessment of radiation enteritis should include the following:[6]

1. The usual pattern of elimination.
2. The pattern of diarrhea, including the following:
1.Onset.
2.Duration.
3.Frequency, amount, and character of stools.
4.Presence of other symptoms such as flatus, cramping, nausea, abdominal distension, tenesmus, bleeding, and rectal excoriation.
3. The nutritional status of the patient, including the following:
1.Height and weight.
2.Usual eating habits, any change in eating habits, and amount of residue in diet.
3.Signs of dehydration such as poor skin turgor, serum electrolyte imbalance, increased weakness, or fatigue.
4. Present level of stress, coping patterns, and impact of signs and symptoms of enteritis on usual lifestyle patterns.

Medical management

Medical management includes treating diarrhea, dehydration, malabsorption, and abdominal or rectal discomfort. Symptoms usually resolve with medications, dietary changes, and rest. If symptoms become severe despite these measures, a treatment break may be warranted.

Medications may include the following:

1. Kaopectate, an antidiarrheal agent. Dose: 30 cc to 60 cc by mouth after each loose bowel movement.
2. Lomotil (diphenoxylate hydrochloride with atropine sulfate). Usual dose: One or two tablets by mouth every 4 hours as needed. Dose can be adjusted to individual patients and patterns of diarrhea. For example, one patient may achieve control of diarrhea with one tablet 3 times a day, while another may require two tablets every 4 hours. Patients are not to take more than eight tablets of Lomotil within a 24-hour period.
3. Paregoric, an antidiarrheal agent. Usual dose: 1 teaspoon by mouth 4 times a day as needed for diarrhea. Paregoric may also be alternated with Lomotil.
4. Cholestyramine, a bile salt sequestering agent. Dose: one package by mouth after each meal and at bedtime.
5. Donnatal, an anticholinergic antispasmodic agent to alleviate bowel cramping. Dose: One or two tablets every 4 hours as needed.
6. Imodium (loperamide hydrochloride), a synthetic antidiarrheal agent. Recommended initial dose: two capsules (4 mg) by mouth every 4 hours, followed by one capsule (2 mg) by mouth after each unformed stool. Daily total dose should not exceed 16 mg (eight capsules).

In addition to these medications, opioids may offer relief from abdominal pain. If proctitis is present, a steroid foam given rectally may offer relief from symptoms. Finally, if patients with pancreatic cancer are experiencing diarrhea during radiation therapy, they should be evaluated for oral pancreatic enzyme replacement, as deficiencies in these enzymes alone can cause diarrhea.

The role of nutrition

Damage to the intestinal villi from radiation therapy results in a reduction or loss of enzymes, one of the most important of these being lactase. Lactase is essential in the digestion of milk and milk products. Although there is no evidence that a lactose-restricted diet will prevent radiation enteritis, a diet that is lactose free, low fat, and low residue can be an effective modality in symptom management.[7]

Foods to avoid

  • Milk and milk products. Exceptions are buttermilk and yogurt, which are often tolerated because lactose is altered by the presence of lactobacillus. Processed cheese may also be tolerated because the lactose is removed with the whey when it is separated from the cheese curd. Milkshake supplements such as Ensure are lactose free and may be used.
  • Whole-bran bread and cereal.
  • Nuts, seeds, and coconuts.
  • Fried, greasy, or fatty foods.
  • Fresh and dried fruit and some fruit juices such as prune juice.
  • Raw vegetables.
  • Rich pastries.
  • Popcorn, potato chips, and pretzels.
  • Strong spices and herbs.
  • Chocolate, coffee, tea, and soft drinks with caffeine.
  • Alcohol and tobacco.

Foods to encourage

  • Fish, poultry, and meat that is cooked, broiled, or roasted.
  • Bananas, applesauce, peeled apples, and apple and grape juices.
  • White bread and toast.
  • Macaroni and noodles.
  • Baked, boiled, or mashed potatoes.
  • Cooked vegetables that are mild, such as asparagus tips, green and waxed beans, carrots, spinach, and squash.
  • Mild processed cheese, eggs, smooth peanut butter, buttermilk, and yogurt.

Helpful hints

  • Ingest food at room temperature.[6]
  • Drink 3,000 cc of fluid per day. Carbonated beverages should be allowed to lose carbonation before being ingested.
  • Add nutmeg to food, which will help decrease mobility of GI tract.
  • Start a low-residue diet on day 1 of radiation therapy treatment.

Chronic Radiation Enteritis

Diagnosis

Only 5% to 15% of the patients who receive abdominal or pelvic irradiation will develop chronic radiation enteritis. Signs and symptoms include colicky abdominal pain, bloody diarrhea, tenesmus, steatorrhea, weight loss, and nausea and vomiting. Less common are bowel obstruction, fistulas, bowel perforation, and massive rectal bleeding.[8] The initial signs and symptoms occur 6 to 18 months after radiation therapy. Radiologic findings include submucosal thickening, single or multiple stenoses, adhesions, and sinus or fistula formation.[9] Microscopic findings include villi that are fibrotic or may be lost altogether. Ulceration is common, varying from simple loss of epithelial layers to ulcers that may penetrate to different depths of the intestinal wall, even to the serosa. Lymphatic tissue is often atrophic or absent. The submucosa is severely diseased. Arterioles and small arteries show profound changes, with hyalinization of the entire wall thickness. The muscularis is often distorted or focally replaced by fibrosis.

The diagnosis of chronic radiation enteritis may be difficult to make. Clinically and radiologically recurrent tumor needs to be ruled out. Because of the possible latency of the illness, it is essential that the physician obtain a detailed history of the patient's radiation therapy course. It is often advisable to include the radiation therapy physician in the continued management of the patient's care.

Treatment

Medical management of the patient's symptoms (which are similar to symptoms of acute radiation enteritis) is indicated, with surgical management reserved for severe damage.[7] Fewer than 2% of the 5% to 15% of patients who received abdominal or pelvic radiation will require surgical intervention.[10]

The timing and choice of surgical techniques remains somewhat controversial. A lower operative mortality (21% vs. 10%) and incidence of anatomic dehiscence (36% vs. 6%) have been reported with intestinal bypass as compared with resection.[11,12] Those who favor resection point out that the removal of diseased bowel decreases the mortality rate for resection and is comparable to the bypass procedure.[11] All agree that simple lysis of adhesions is inadequate and that fistulas require bypass.

Surgery should be undertaken only after careful assessment of the patient's clinical condition and extent of radiation damage because wound healing is often delayed, necessitating prolonged parenteral feeding after surgery. Even after apparently successful operations, symptoms may persist in a significant proportion of patients.[13]

Prevention

Treatment techniques that can minimize the risk of severe radiation enteritis include the following:

1. Radiation therapy techniques:
1.The use of a three- or four-field technique (as opposed to a two-field technique) to minimize the amount of small bowel exposed to treatment.
2.The treatment of the patient in a physical position that will aid in removing as much small bowel from the treatment field as possible for example, treating a patient with a full bladder each day to aid in pushing the small bowel up and out of the pelvis when pelvic radiation is given).
3.Daily treatment of all fields, resulting in a lower integral dose and more homogenous dose distribution.
4.Use of computerized radiation dosimetry to best design the treatment plan and the use of high-energy treatment machines such as linear accelerators that deliver a high dose-to-tumor volume while sparing the normal structures.[14]
2. Surgery. Placing clips in high-risk areas to better define the location or former location of the tumor and aid in radiation treatment planning.
3. Modification of treatment sequencing. An area for exploration is the sequencing of radiation, chemotherapy, and surgery and its influence on the severity of enteritis.

References:

1. O'Brien PH, Jenrette JM 3rd, Garvin AJ: Radiation enteritis. Am Surg 53 (9): 501-4, 1987.
2. Yeoh EK, Horowitz M: Radiation enteritis. Surg Gynecol Obstet 165 (4): 373-9, 1987.
3. Gallagher MJ, Brereton HD, Rostock RA, et al.: A prospective study of treatment techniques to minimize the volume of pelvic small bowel with reduction of acute and late effects associated with pelvic irradiation. Int J Radiat Oncol Biol Phys 12 (9): 1565-73, 1986.
4. Haddad GK, Grodsinsky C, Allen H: The spectrum of radiation enteritis. Surgical considerations. Dis Colon Rectum 26 (9): 590-4, 1983.
5. Alimentary tract. In: Fajardo LF: Pathology of Radiation Injury. New York: Masson Publishers, 1982, pp 47-76.
6. Yasko JM: Care of the Client Receiving External Radiation Therapy. Reston, Va: Reston Publishing Company, Inc., 1982.
7. Stryker JA, Bartholomew M: Failure of lactose-restricted diets to prevent radiation-induced diarrhea in patients undergoing whole pelvis irradiation. Int J Radiat Oncol Biol Phys 12 (5): 789-92, 1986.
8. Kinsella TJ, Bloomer WD: Tolerance of the intestine to radiation therapy. Surg Gynecol Obstet 151 (2): 273-84, 1980.
9. Mendelson RM, Nolan DJ: The radiological features of chronic radiation enteritis. Clin Radiol 36 (2): 141-8, 1985.
10. Galland RB, Spencer J: Surgical management of radiation enteritis. Surgery 99 (2): 133-9, 1986.
11. Lillemoe KD, Brigham RA, Harmon JW, et al.: Surgical management of small-bowel radiation enteritis. Arch Surg 118 (8): 905-7, 1983.
12. Wobbes T, Verschueren RC, Lubbers EJ, et al.: Surgical aspects of radiation enteritis of the small bowel. Dis Colon Rectum 27 (2): 89-92, 1984.
13. Wellwood JM, Jackson BT: The intestinal complications of radiotherapy. Br J Surg 60 (10): 814-8, 1973.
14. Minsky BD, Cohen AM: Minimizing the toxicity of pelvic radiation therapy in rectal cancer. Oncology (Huntingt) 2 (8): 21-5, 28-9, 1988.

Current Clinical Trials

Check NCI's PDQ Cancer Clinical Trials Registry for U.S. supportive and palliative care trials about gastrointestinal complications that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Get More Information From NCI

CALL 1-800-4-CANCER

For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 a.m. to 4:30 p.m. A trained Cancer Information Specialist is available to answer your questions.

CHAT ONLINE

The NCI's LiveHelp® online chat service provides Internet users with the ability to chat online with an Information Specialist. The service is available from 9:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer.

WRITE TO US

For more information from the NCI, please write to this address:

NCI Public Inquiries Office
Suite 3036A
6116 Executive Boulevard, MSC8322
Bethesda, MD 20892-8322

SEARCH THE NCI WEB SITE

The NCI Web site provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. For a quick search, use the search box in the upper right corner of each Web page. The results for a wide range of search terms will include a list of "Best Bets," editorially chosen Web pages that are most closely related to the search term entered.

There are also many other places to get materials and information about cancer treatment and services. Hospitals in your area may have information about local and regional agencies that have information on finances, getting to and from treatment, receiving care at home, and dealing with problems related to cancer treatment.

FIND PUBLICATIONS

The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237).

Changes to This Summary (01 / 15 / 2010)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

CONSTIPATION

Added text adapted from the MD Anderson Cancer Center practice consensus algorithm for the prevention and management of opioid-induced constipation.

Added a caution to administer opioid antagonists only if other drugs have failed.

DIARRHEA

Added text on probiotics (cited de Vrese et al. as reference 32, Johnston et al. as reference 34, Pillai et al. as reference 35, Huertas-Ceballos et al. as reference 36, Alfaleh et al. as reference 37, Karimi et al. as reference 38, Butterworth et al. as reference 39, and Delia et al. as reference 40).

Questions or Comments About This Summary

If you have questions or comments about this summary, please send them to Cancer.gov through the Web site's Contact Form. We can respond only to email messages written in English.

More Information

ABOUT PDQ

  • PDQ® - NCI's Comprehensive Cancer Database.
    Full description of the NCI PDQ database.

ADDITIONAL PDQ SUMMARIES

  • PDQ® Cancer Information Summaries: Adult Treatment
    Treatment options for adult cancers.
  • PDQ® Cancer Information Summaries: Pediatric Treatment
    Treatment options for childhood cancers.
  • PDQ® Cancer Information Summaries: Supportive and Palliative Care
    Side effects of cancer treatment, management of cancer-related complications and pain, and psychosocial concerns.
  • PDQ® Cancer Information Summaries: Screening/Detection (Testing for Cancer)
    Tests or procedures that detect specific types of cancer.
  • PDQ® Cancer Information Summaries: Prevention
    Risk factors and methods to increase chances of preventing specific types of cancer.
  • PDQ® Cancer Information Summaries: Genetics
    Genetics of specific cancers and inherited cancer syndromes, and ethical, legal, and social concerns.
  • PDQ® Cancer Information Summaries: Complementary and Alternative Medicine
    Information about complementary and alternative forms of treatment for patients with cancer.

IMPORTANT:

This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

Date Last Modified: 2010-01-15

related physicians

related services

Bon Secours International| Sisters of Bon Secours USA| Bon Secours Health System

This information does not replace the advice of a doctor. Healthwise disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use. Privacy Policy. How this information was developed to help you make better health decisions.