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This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the pathophysiology and treatment of gastrointestinal complications, including constipation, impaction, bowel obstruction, diarrhea, and radiation enteritis. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

This summary is reviewed regularly and updated as necessary by the PDQ Supportive and Palliative Care Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

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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 the following three means:

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 do the following:

Diarrhea, in some cases, can 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. One report also documented radiation-induced diarrhea as a result of radiation for lung and head and neck cancers in individuals who were receiving radiation with or without chemotherapy.[ 5 ]

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.[ 6 ]

In this summary, unless otherwise stated, evidence and practice issues as they relate to adults are discussed. The evidence and application to practice related to children may differ significantly from information related to adults. When specific information about the care of children is available, it is summarized under its own heading.

参考文献

Culhane B: Constipation. In: Yasko J, ed.: Guidelines for Cancer Care: Symptom Management. Reston, Va: Reston Publishing Company, Inc., 1983, pp 184-7.[PUBMED Abstract]
Wright BA, Staats DO: The geriatric implications of fecal impaction. Nurse Pract 11 (10): 53-8, 60, 64-6, 1986.[PUBMED Abstract]
Hampton BG, Bryant RA, eds.: Ostomies and Continent Diversions: Nursing Management. St. Louis, Mo: Mosby Year Book, Inc., 1992.[PUBMED Abstract]
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.[PUBMED Abstract]
Sonis S, Elting L, Keefe D, et al.: Unanticipated frequency and consequences of regimen-related diarrhea in patients being treated with radiation or chemoradiation regimens for cancers of the head and neck or lung. Support Care Cancer 23 (2): 433-9, 2015.[PUBMED Abstract]
Perez CA, Brady LW, eds.: Principles and Practice of Radiation Oncology. 3rd ed. Philadelphia, Pa: Lippincott-Raven Publishers, 1998.[PUBMED Abstract]

Constipation

Etiology of Constipation

Common factors that contribute to the development of constipation in the general population include the following:

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 following:[ 1 ]

Physiologic factors include the following:

Any or all of these factors can occur because of the disease process, aging, debilitation, or treatment.

Causes of Constipation

[Note: *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 will 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 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 Constipation section in the Adverse effects section of the PDQ summary on Cancer 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 will 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 is 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, dietary changes, and medications, along with a physical examination, can identify possible causes of constipation. The evaluation also includes assessment of associated symptoms such as distention, flatus, cramping, or rectal fullness. A digital rectal examination is 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:

What is normal for the patient (frequency, amount, and timing)?
When was the last bowel movement? What was the amount, consistency, and color? Was blood passed with it?
Has the patient been having any abdominal discomfort, cramping, nausea or vomiting, pain, excessive gas, or rectal fullness?
Does the patient regularly use laxatives or enemas? What does the patient usually do to relieve constipation? Does it usually work?
What type of diet does the patient follow? How much and what type of fluids are taken on a regular basis?
What medication (dose and frequency) is the patient taking?
Is this symptom a recent change?
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 are assessed for constipation. Dietary habits, fluid intake, activity levels, and use of opioids in these patients are examined.

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 indicated lower costs, more natural and regular bowel movements, and increased ease of administration with natural laxatives. Even though generalization from these findings was 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.

Commonly used interventions:

Record bowel movements daily.
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 consumes 15 g of fiber per day (10 + 5). This guideline applies until age 18 years; at that time, the adult recommendations are followed.
  While there are no specific fiber recommendations for cancer patients, they are 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. [Note: Copyright 2008 The University of Texas MD Anderson Cancer Center]

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

Assess potential cause of constipation (e.g., recent opioid dose increase, use of other constipating medications, or new bowel obstruction).
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.
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.
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, one to two capsules per day). For opioid-related constipation, stool softeners may 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) is 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.

Contraindications

Rectal agents should be avoided in cancer patients at risk of thrombocytopenia, leukopenia, and/or mucositis from cancer and its treatment. In the immunocompromised patient, manipulation of the rectum and anus should be avoided (i.e., 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 unnecessarily.

Transanal irrigation (TAI) is a recently described therapeutic modality intended to manage chronic neurogenic and anatomic colonic dysmotility resulting in chronic constipation or fecal incontinence.[ 6 ] Several studies have found greater efficacy with TAI than with conventional management strategies for neurogenic bowel dysfunction;[ 7 ][ 8 ][ 9 ] however, no studies have shown either safety or efficacy in people with constipation related directly to a tumor or caused by treatment for cancer or side-effect management (e.g., opioid-induced constipation). Complications, although rare in the currently indicated populations, include bowel perforation.[ 10 ][ 11 ] Colon cancer, history of any colorectal surgery, and pelvic radiation are considered relative or absolute contraindications to using TAI.[ 6 ]

At this time, for patients with cancer or a history of cancer, the evidence does not support the use of TAI for management of chronic constipation or fecal incontinence for conditions other than neurogenic dysfunction.

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 take the bulk producer 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 of 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.

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 are not 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; increase daily fluid intake.
- Poloxamer 188: 188 mg (480 mg at bedtime).

Opioid antagonists (naloxone, methylnaltrexone, naldemedine)

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 noncancer 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.[ 12 ][ 13 ]
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.[ 14 ]
A study of daily oral naldemedine, 0.2 mg for 2 weeks, demonstrated improved bowel function from baseline compared with placebo. There was no associated opioid withdrawal or decrease in opioid-mediated analgesia.[ 15 ]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

参考文献

Portenoy RK: Constipation in the cancer patient: causes and management. Med Clin North Am 71 (2): 303-11, 1987.[PUBMED Abstract]
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.[PUBMED Abstract]
McShane RE, McLane AM: Constipation. Consensual and empirical validation. Nurs Clin North Am 20 (4): 801-8, 1985.[PUBMED Abstract]
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.[PUBMED Abstract]
Beverley L, Travis I: Constipation: proposed natural laxative mixtures. J Gerontol Nurs 18 (10): 5-12, 1992.[PUBMED Abstract]
Emmanuel AV, Krogh K, Bazzocchi G, et al.: Consensus review of best practice of transanal irrigation in adults. Spinal Cord 51 (10): 732-8, 2013.[PUBMED Abstract]
Christensen P, Bazzocchi G, Coggrave M, et al.: A randomized, controlled trial of transanal irrigation versus conservative bowel management in spinal cord-injured patients. Gastroenterology 131 (3): 738-47, 2006.[PUBMED Abstract]
Krogh K, Ostergaard K, Sabroe S, et al.: Clinical aspects of bowel symptoms in Parkinson's disease. Acta Neurol Scand 117 (1): 60-4, 2008.[PUBMED Abstract]
Coggrave M, Norton C, Cody JD: Management of faecal incontinence and constipation in adults with central neurological diseases. Cochrane Database Syst Rev 1: CD002115, 2014.[PUBMED Abstract]
Christensen P, Krogh K, Buntzen S, et al.: Long-term outcome and safety of transanal irrigation for constipation and fecal incontinence. Dis Colon Rectum 52 (2): 286-92, 2009.[PUBMED Abstract]
Memon S, Bissett IP: Rectal perforation following transanal irrigation. ANZ J Surg 86 (5): 412-3, 2016.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
Katakami N, Harada T, Murata T, et al.: Randomized Phase III and Extension Studies of Naldemedine in Patients With Opioid-Induced Constipation and Cancer. J Clin Oncol 35 (34): 3859-3866, 2017.[PUBMED Abstract]

Impaction

Etiology of Impaction

Five major factors precipitating impaction include the following:

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 is 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 is 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 are avoided so that the bowel is not damaged further.

Current Clinical Trials

参考文献

Cefalu CA, McKnight GT, Pike JI: Treating impaction: a practical approach to an unpleasant problem. Geriatrics 36 (5): 143-6, 1981.[PUBMED Abstract]
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.[PUBMED Abstract]
Brandt LJ: Gastrointestinal Disorders of the Elderly. New York, NY: Raven Press, 1984.[PUBMED Abstract]

Large or Small Bowel Obstruction

The four types of obstruction include the following:

Simple.
Closed-loop.
Strangulated.
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 such as:[ 1 ]

Nonmechanical factors include those that interfere with the muscle action or innervation of the bowel such as:

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.

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 may 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 ][Level of evidence: II][ 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% of patients.[ 11 ]

For some patients with malignant obstructions of the gastrointestinal tract, the use of expandable metal stents may provide palliation of obstructive symptoms. Esophageal, biliary, gastroduodenal, and colorectal stents are available.[ 5 ][ 12 ][ 13 ][ 14 ][ 15 ][ 16 ][ 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 ][Level of evidence: II][ 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 of gastrointestinal secretions may be produced per day. 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 somatostatin analog octreotide. This agent inhibits the release of several gastrointestinal hormones and reduces gastrointestinal secretions.[ 22 ][ 23 ][Level of evidence: I][ 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 ]

Current Clinical Trials

参考文献

Givens BA, Simmons SJ: Gastroenterology in Clinical Nursing. 4th ed. St. Louis, Mo: C.V. Mosby Co, 1984.[PUBMED Abstract]
Bouchier IA: Gastroenterology. 3rd ed. London: Balliere Tindall, 1982.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
Ripamonti C, Bruera E: Palliative management of malignant bowel obstruction. Int J Gynecol Cancer 12 (2): 135-43, 2002 Mar-Apr.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
Aviv RI, Shyamalan G, Watkinson A, et al.: Radiological palliation of malignant colonic obstruction. Clin Radiol 57 (5): 347-51, 2002.[PUBMED Abstract]
Dauphine CE, Tan P, Beart RW, 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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
Baron TH, Rey JF, Spinelli P: Expandable metal stent placement for malignant colorectal obstruction. Endoscopy 34 (10): 823-30, 2002.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
Fallon MT: The physiology of somatostatin and its synthetic analogue, octreotide. European Journal of Palliative Care 1 (1): 20-2, 1994.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]

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 Terminology Criteria for Adverse Events, more than half of patients receiving chemotherapy for colorectal cancer experienced diarrhea of grade 3 or grade 4, requiring treatment changes or the reduction, delay, or discontinuation of therapy (refer to 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 Terminology Criteria for Adverse Events: Diarrhea^a,b
Grade	Description
ADL = activities of daily living.
^aAdapted from National Cancer Institute.[ 8 ]
^bDefinition: A disorder characterized by an increase in frequency and/or loose or watery bowel movements.
^cInstrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc.
^dSelf-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.
1	Increase of <4 stools/day over baseline; mild increase in ostomy output compared with baseline
2	Increase of 4–6 stools/day over baseline; moderate increase in ostomy output compared with baseline; limiting instrumental ADL^c
3	Increase of ≥7 stools/day over baseline; hospitalization indicated; severe increase in ostomy output compared with baseline; limiting self-care ADL^d
4	Life-threatening consequences; urgent intervention indicated
5	Death

Etiology of Diarrhea

In patients being treated for cancer, diarrhea is most commonly induced by therapy.[ 11 ] Conventional methods of diarrhea-causing treatment include the following:

Other causes of acute diarrhea include the following:[ 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 (refer to 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) factors 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 the following:[ 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. 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 the following:

Common side effects of intestinal enteritis include the following:

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. (Refer to the Radiation Enteritis section of this summary for more information.)

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 Patients
Cancer [ 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 [ 14 ]	Celiac plexus block
	Cholecystectomy, esophagogastrectomy
	Gastrectomy, pancreaticoduodenectomy (Whipple procedure)
	Intestinal resection (malabsorption due to short bowel syndrome)
	Vagotomy
Chemotherapy [ 19 ][ 20 ][ 21 ]; [ 22 ][Level of evidence: IV]	Capecitabine, cisplatin, cytosine arabinoside, cyclophosphamide, daunorubicin, docetaxel, doxorubicin, 5-fluorouracil, interferon, irinotecan, leucovorin, methotrexate, oxaliplatin, paclitaxel, topotecan, lapatinib, pertuzumab
Radiation therapy (Refer to the Radiation Enteritis section of this summary for more information.) [ 23 ][ 24 ][ 25 ]	Irradiation to the abdomen, para-aortics, lumbar, and pelvis or radiation for lung and head and neck cancers
Bone marrow transplantation [ 26 ]	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, lactulose, laxatives, methyldopa, metoclopramide, misoprostol, potassium supplements, propranolol, theophylline
Concurrent disease [ 5 ][ 18 ]	Diabetes, hyperthyroidism, inflammatory bowel disease (Crohn disease, diverticulitis, gastroenteritis, HIV/AIDS, ulcerative colitis), obstruction (tumor related)
Infection [ 27 ]	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-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

Rapid, yet thorough, assessment of diarrhea is imperative because of the potentially life-threatening nature of diarrhea. 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 Terminology Criteria for Adverse Events (refer to Table 1) evaluate diarrhea by the following:[ 8 ]

The history also includes 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.[ 28 ] One author has developed a visual tool to assist patients and families in characterizing the consistency of the stool.[ 29 ] Six diagrams illustrate fecal material consistency ranging from well-formed, formed, and semiformed to loose, very loose, and liquid.

Patients are questioned regarding related symptoms that might indicate hemodynamic compromise or the underlying etiology. Specific questions include information about the following:

These symptoms are classified as complicated or uncomplicated, with therapy based on these classifications.[ 30 ]

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:

Grade 3 or 4 diarrhea is also classified as complicated. Thorough evaluation and close monitoring is warranted.[ 30 ]

The time course of diarrhea and concomitant symptom development are key to determining underlying etiology.[ 28 ] 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. National Cancer Institute’s Common Terminology Criteria for Adverse Events: Nausea and Vomiting^a
Adverse Event	Grade	Description
IV = intravenous; TPN = total parenteral nutrition.
^aAdapted from National Cancer Institute.[ 8 ]
^bDefinition: A disorder characterized by a queasy sensation and/or the urge to vomit.
^cDefinition: A disorder characterized by the reflexive act of ejecting the contents of the stomach through the mouth.
Nausea^b	1	Loss of appetite without alteration in eating habits
	2	Oral intake decreased without significant weight loss, dehydration, or malnutrition
	3	Inadequate oral caloric or fluid intake; tube feeding, TPN, or hospitalization indicated
	4	Grade not assigned
	5	Grade not assigned
Vomiting^c	1	Intervention not indicated
	2	Outpatient IV hydration; medical intervention indicated
	3	Tube feeding, TPN, or hospitalization indicated
	4	Life-threatening consequences; urgent intervention indicated
	5	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 includes 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 is 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.[ 30 ]

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) are discontinued. Dietary modifications are commonly implemented to stop or lessen the severity of cancer treatment-related diarrhea.[ 7 ][ 24 ][ 26 ][ 31 ] In some cases, dietary modification for diarrhea management includes advising patients to eat small, frequent meals and avoid the following:[ 32 ]

For mild cases of diarrhea, the BRAT (bananas, rice, applesauce, toast) diet may reduce the frequency of stools. When experiencing diarrhea, patients are encouraged to increase their intake of clear liquids to at least 3 L per day (e.g., water, sports drinks, broth, weak decaffeinated teas, caffeine-free soft drinks, clear juices, and gelatin).[ 12 ][ 33 ] (Refer to the Behavioral strategies for symptom management section in the Nutrition Therapy section of the PDQ summary on Nutrition in Cancer Care for more information.)

While some case reports suggest the efficacy of glutamine in relieving diarrhea and other gastrointestinal symptoms associated with cancer therapy, one randomized controlled trial that used oral glutamine to prevent pelvic radiation-induced diarrhea was unable to demonstrate any benefit.[ 34 ][Level of evidence: I][ 35 ][ 36 ]

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.[ 5 ][ 28 ] Regardless of the dose, however, loperamide may be less effective in patients with grade 3 or 4 diarrhea.[ 37 ][Level of evidence: I]

Mucosal prostaglandin inhibitors, also referred to as antisecretory agents, include the following:

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.[ 38 ] 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.[ 39 ][Level of evidence: II] 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 with 32 patients receiving the same chemotherapeutic regimen without oral alkalization and controlled defecation.[ 40 ][Level of evidence: III]

In addition to antidiarrheal agents and immunosuppressive medications, a specialized five-phase dietary regimen may be instituted to effectively manage diarrhea associated with GVHD.[ 26 ]

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 the beverages in phase 2 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.

Probiotics

Probiotics are nutritional supplements that contain a defined amount of viable microorganisms and, upon administration, confer a benefit to the patient.[ 41 ] 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.[ 42 ] 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:[ 43 ][ 44 ][ 45 ][ 46 ][ 47 ][ 48 ]

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.[ 49 ]

Complicated symptoms

While the optimal dose of octreotide has not been determined, a panel of experts has recommended that complicated cases of diarrhea be managed with intravenous (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 continues until the patient has been diarrhea free for 24 hours.[ 30 ] Particularly when patients are receiving chemotherapy, additional evaluation includes stool workup (including blood, fecal leukocytes, C. difficile, Salmonella, E. coli, Campylobacter, and infectious colitis), complete blood count, and electrolyte profile.[ 30 ] This workup and treatment is also 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 are 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.[ 50 ][Level of evidence: II][ 18 ] Several open-label and randomized controlled studies of octreotide in the relief of chemotherapy-induced diarrhea have demonstrated the efficacy of this therapy.[ 51 ][ 52 ][ 53 ][Level of evidence: I];[ 54 ][ 55 ][ 56 ][Level of evidence: II] In a prospective trial of 32 patients who had chemotherapy-induced diarrhea that was refractory to loperamide, octreotide 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.[ 57 ] Octreotide has also been shown to be effective in diarrhea associated with GVHD.[ 58 ][ 59 ]

An expert panel recommended using high-dose loperamide (2 mg q2h) for the first day of chemotherapy-induced diarrhea that is low grade (grade 1 or 2), followed by octreotide (100 µg–150 µg q8h).[ 28 ] If the patient presents with severe diarrhea (grade 3 or 4), octreotide (500 μg–1,500 µg SC or IV q8h) may be given as 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.[ 60 ] 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 more information.)

Unique scenarios

Irinotecan

Irinotecan is notorious for causing diarrhea. Irinotecan is associated with both acute diarrhea (occurring immediately after drug administration) and delayed diarrhea (occurring more than 24 hours after drug administration). Acute diarrhea is related to acute cholinergic excess and thus responds well to atropine. Delayed diarrhea, however, is typically managed with antidiarrheals and other supportive measures, as outlined above.[ 61 ]

Immune checkpoint inhibitors

Immune-mediated colitis is a potential side effect of immune checkpoint inhibitors (ICIs). CTLA-4 inhibitors typically cause diarrhea and colitis more frequently than do PD-1 and PD-L1 inhibitors, with the highest rates of colitis seen in patients receiving a combination of ICIs.[ 62 ] The onset of these events can be unpredictable but typically occurs within the first ten doses of an ICI and may occur after cessation of an ICI.[ 63 ] Symptoms are treated according to the grade of diarrhea/colitis. Patients with mild diarrhea/colitis may be managed symptomatically with fluids and antidiarrheals, but more severe diarrhea/colitis may necessitate treatment with systemic steroids and even permanent discontinuation of ICI therapy. Detailed management of ICI-induced diarrhea is further outlined in National Comprehensive Cancer Network guidelines for the management of immunotherapy-related toxicities.[ 64 ]

Phosphatidylinositol 3-kinase (PI3K) inhibitors

Four PI3K inhibitors have been approved by the U.S. Food and Drug Administration, two of which (idelalisib and duvelisib) carry a boxed warning for gastrointestinal complications, including diarrhea.[ 65 ][ 66 ] Given the severity of diarrhea that may be seen with idelalisib, an expert panel convened to develop management strategies for idelalisib-associated diarrhea.[ 67 ] Panelists commented that it is not clear whether diarrhea is a class effect of PI3K inhibitors. The authors noted that for idelalisib, two types of diarrhea may be seen: the first type appears to be self-limiting, occurring within the first 8 weeks of treatment; the second type tends to respond poorly to antidiarrheal therapy and occurs later in treatment (approximately 7 months after the start of treatment). In the second type of diarrhea, the histologic appearance of the colon is consistent with lymphocytic colitis; therefore, the panel recommended considering treatment with steroids or budesonide.[ 67 ]

Current Clinical Trials

参考文献

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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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
National Cancer Institute: Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. Bethesda, Md: U.S. Department of Health and Human Services, National Institutes of Health, 2017. Available online. Last accessed May 20, 2020.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
Bruckstein AH: Acute diarrhea. Am Fam Physician 38 (4): 217-28, 1988.[PUBMED Abstract]
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.[PUBMED Abstract]
Grant JP, Chapman G, Russell MK: Malabsorption associated with surgical procedures and its treatment. Nutr Clin Pract 11 (2): 43-52, 1996.[PUBMED Abstract]
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.[PUBMED Abstract]
Herrmann VM, Petruska PJ: Nutrition support in bone marrow transplant recipients. Nutr Clin Pract 8 (1): 19-27, 1993.[PUBMED Abstract]
Mercadante S: Diarrhea in terminally ill patients: pathophysiology and treatment. J Pain Symptom Manage 10 (4): 298-309, 1995.[PUBMED Abstract]
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.[PUBMED Abstract]
Wadler S, Benson AB, Engelking C, et al.: Recommended guidelines for the treatment of chemotherapy-induced diarrhea. J Clin Oncol 16 (9): 3169-78, 1998.[PUBMED Abstract]
Crown JP, Burris HA, 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.[PUBMED Abstract]
Swain SM, Schneeweiss A, Gianni L, et al.: Incidence and management of diarrhea in patients with HER2-positive breast cancer treated with pertuzumab. Ann Oncol 28 (4): 761-768, 2017.[PUBMED Abstract]
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.[PUBMED Abstract]
Donaldson SS: Nutritional consequences of radiotherapy. Cancer Res 37 (7 Pt 2): 2407-13, 1977.[PUBMED Abstract]
Sonis S, Elting L, Keefe D, et al.: Unanticipated frequency and consequences of regimen-related diarrhea in patients being treated with radiation or chemoradiation regimens for cancers of the head and neck or lung. Support Care Cancer 23 (2): 433-9, 2015.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
Mertz HR, Beck CK, Dixon W, et al.: Validation of a new measure of diarrhea. Dig Dis Sci 40 (9): 1873-82, 1995.[PUBMED Abstract]
Benson AB, Ajani JA, Catalano RB, et al.: Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol 22 (14): 2918-26, 2004.[PUBMED Abstract]
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.[PUBMED Abstract]
McCallum PD, Polisena CG, eds.: The Clinical Guide to Oncology Nutrition. Chicago, Ill: The American Dietetic Association, 2000.[PUBMED Abstract]
Hogan CM: The nurse's role in diarrhea management. Oncol Nurs Forum 25 (5): 879-86, 1998.[PUBMED Abstract]
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.[PUBMED Abstract]
Savy GK: Glutamine supplementation. Heal the gut, help the patient. J Infus Nurs 25 (1): 65-9, 2002 Jan-Feb.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
Creemers GJ, Lund B, Verweij J: Topoisomerase I inhibitors: topotecan and irenotecan. Cancer Treat Rev 20 (1): 73-96, 1994.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
de Vrese M, Schrezenmeir J: Probiotics, prebiotics, and synbiotics. Adv Biochem Eng Biotechnol 111: 1-66, 2008.[PUBMED Abstract]
Isolauri E: Probiotics in human disease. Am J Clin Nutr 73 (6): 1142S-1146S, 2001.[PUBMED Abstract]
Johnston BC, Supina AL, Ospina M, et al.: Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev (2): CD004827, 2007.[PUBMED Abstract]
Pillai A, Nelson R: Probiotics for treatment of Clostridium difficile-associated colitis in adults. Cochrane Database Syst Rev (1): CD004611, 2008.[PUBMED Abstract]
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.[PUBMED Abstract]
Alfaleh K, Bassler D: Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev (1): CD005496, 2008.[PUBMED Abstract]
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.[PUBMED Abstract]
Butterworth AD, Thomas AG, Akobeng AK: Probiotics for induction of remission in Crohn's disease. Cochrane Database Syst Rev (3): CD006634, 2008.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
Zidan J, Haim N, Beny A, et al.: Octreotide in the treatment of severe chemotherapy-induced diarrhea. Ann Oncol 12 (2): 227-9, 2001.[PUBMED Abstract]
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.[PUBMED Abstract]
Morton AJ, Durrant ST: Efficacy of octreotide in controlling refractory diarrhea following bone marrow transplantation. Clin Transplant 9 (3 Pt 1): 205-8, 1995.[PUBMED Abstract]
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.[PUBMED Abstract]
Stein A, Voigt W, Jordan K: Chemotherapy-induced diarrhea: pathophysiology, frequency and guideline-based management. Ther Adv Med Oncol 2 (1): 51-63, 2010.[PUBMED Abstract]
Tandon P, Bourassa-Blanchette S, Bishay K, et al.: The Risk of Diarrhea and Colitis in Patients With Advanced Melanoma Undergoing Immune Checkpoint Inhibitor Therapy: A Systematic Review and Meta-Analysis. J Immunother 41 (3): 101-108, 2018.[PUBMED Abstract]
Rocha M, Correia de Sousa J, Salgado M, et al.: Management of Gastrointestinal Toxicity from Immune Checkpoint Inhibitor. GE Port J Gastroenterol 26 (4): 268-274, 2019.[PUBMED Abstract]
National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Management of Immunotherapy-Related Toxicities. Version 1.2020. Plymouth Meeting, Pa: National Comprehensive Cancer Network, 2019. Available online with free registration. Last accessed January 6, 2020.[PUBMED Abstract]
ZYDELIG (idelalisib): highlights of prescribing information. Foster City, Calif: Gilead Sciences, Inc., 2018. Available online. Last accessed January 3, 2020.[PUBMED Abstract]
COPIKTRA (duvelisib): highlights of prescribing information. Needham, Mass: Verastem Inc, 2018. Available online. Last accessed January 3, 2020.[PUBMED Abstract]
Coutré SE, Barrientos JC, Brown JR, et al.: Management of adverse events associated with idelalisib treatment: expert panel opinion. Leuk Lymphoma 56 (10): 2779-86, 2015.[PUBMED Abstract]

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:

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.

One study of radiation for lung and head and neck cancers, with or without accompanying chemotherapy, noted significant diarrhea despite no direct radiation to the large or small intestine. Higher rates were noted for chemoradiation (42%) than for radiation alone (29%). Additionally, this radiation-induced diarrhea was associated with worse health outcomes and increased resource utilization. Individuals with moderate or worse diarrhea were more likely to have gastrostomy tube placement, weight loss, unplanned office visits, more inpatient days, and longer radiation breaks. This early report requires additional validation studies to fully evaluate the prevalence and impact of this phenomenon.[ 5 ]

Acute enteritis symptoms usually resolve 2 to 3 weeks after the completion of treatment, and the mucosa may appear nearly normal.[ 6 ]

Assessment

Patient examination and assessment of radiation enteritis includes the following:[ 7 ]

The usual pattern of elimination.
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.
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.
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:

Kaopectate, an antidiarrheal agent. Dose: 30 cc to 60 cc by mouth after each loose bowel movement.
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 patient may require two tablets every 4 hours. Patients are not to take more than eight tablets of Lomotil within a 24-hour period.
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.
Cholestyramine, a bile salt sequestering agent. Dose: one package by mouth after each meal and at bedtime.
Donnatal, an anticholinergic antispasmodic agent to alleviate bowel cramping. Dose: One or two tablets every 4 hours as needed.
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 will 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.[ 8 ][Level of evidence: I]

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 the following:

Less common are bowel obstruction, fistulas, bowel perforation, and massive rectal bleeding.[ 9 ]

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.[ 10 ] 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.[ 8 ][Level of evidence: I] Fewer than 2% of the 5% to 15% of patients who received abdominal or pelvic radiation will require surgical intervention.[ 11 ]

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.[ 12 ][Level of evidence: II][ 13 ] 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.[ 12 ] All agree that simple lysis of adhesions is inadequate and that fistulas require bypass.

Surgery is 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.[ 14 ]

Prevention

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

Radiation therapy techniques, including the following:
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 (e.g., 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.[ 15 ]
Surgery. Placing clips in high-risk areas to better define the location or former location of the tumor and aid in radiation treatment planning.
Modification of treatment sequencing. An area for exploration is the sequencing of radiation, chemotherapy, and surgery and its influence on the severity of enteritis.

参考文献

O'Brien PH, Jenrette JM, Garvin AJ: Radiation enteritis. Am Surg 53 (9): 501-4, 1987.[PUBMED Abstract]
Yeoh EK, Horowitz M: Radiation enteritis. Surg Gynecol Obstet 165 (4): 373-9, 1987.[PUBMED Abstract]
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.[PUBMED Abstract]
Haddad GK, Grodsinsky C, Allen H: The spectrum of radiation enteritis. Surgical considerations. Dis Colon Rectum 26 (9): 590-4, 1983.[PUBMED Abstract]
Sonis S, Elting L, Keefe D, et al.: Unanticipated frequency and consequences of regimen-related diarrhea in patients being treated with radiation or chemoradiation regimens for cancers of the head and neck or lung. Support Care Cancer 23 (2): 433-9, 2015.[PUBMED Abstract]
Alimentary tract. In: Fajardo LF: Pathology of Radiation Injury. New York: Masson Publishers, 1982, pp 47-76.[PUBMED Abstract]
Yasko JM: Care of the Client Receiving External Radiation Therapy. Reston, Va: Reston Publishing Company, Inc., 1982.[PUBMED Abstract]
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.[PUBMED Abstract]
Kinsella TJ, Bloomer WD: Tolerance of the intestine to radiation therapy. Surg Gynecol Obstet 151 (2): 273-84, 1980.[PUBMED Abstract]
Mendelson RM, Nolan DJ: The radiological features of chronic radiation enteritis. Clin Radiol 36 (2): 141-8, 1985.[PUBMED Abstract]
Galland RB, Spencer J: Surgical management of radiation enteritis. Surgery 99 (2): 133-9, 1986.[PUBMED Abstract]
Lillemoe KD, Brigham RA, Harmon JW, et al.: Surgical management of small-bowel radiation enteritis. Arch Surg 118 (8): 905-7, 1983.[PUBMED Abstract]
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.[PUBMED Abstract]
Wellwood JM, Jackson BT: The intestinal complications of radiotherapy. Br J Surg 60 (10): 814-8, 1973.[PUBMED Abstract]
Minsky BD, Cohen AM: Minimizing the toxicity of pelvic radiation therapy in rectal cancer. Oncology (Huntingt) 2 (8): 21-5, 28-9, 1988.[PUBMED Abstract]

Changes to This Summary (04/22/2020)

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

Updated Memon et al. as reference 11.

Diarrhea

Added immunotherapy as a conventional method of diarrhea-causing treatment.

Added Unique scenarios as a new subsection.

This summary is written and maintained by the PDQ Supportive and Palliative Care Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

Reviewers and Updates

Board members review recently published articles each month to determine whether an article should:

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Supportive and Palliative Care Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”

The preferred citation for this PDQ summary is:

PDQ® Supportive and Palliative Care Editorial Board. PDQ Gastrointestinal Complications. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/treatment/side-effects/constipation/GI-complications-hp-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389211]

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医療専門家向け Gastrointestinal Complications (PDQ®)

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CONTENTS 全て開く全て閉じる

Etiology of Constipation

Causes of Constipation

Assessment of Constipation

Management of Constipation

Contraindications

Medical Agents for Constipation

Current Clinical Trials

Etiology of Impaction

Signs and Symptoms of Impaction

Assessment of Impaction

Treatment of Impaction

Current Clinical Trials

Etiology of Bowel Obstruction

Assessment and Diagnosis of Bowel Obstruction

Treatment of Acute Bowel Obstruction

Management of Chronic, Malignant Bowel Obstruction

Current Clinical Trials

Etiology of Diarrhea

Assessment

Management

Uncomplicated symptoms

Probiotics

Complicated symptoms

Unique scenarios

Irinotecan

Immune checkpoint inhibitors

Phosphatidylinositol 3-kinase (PI3K) inhibitors

Current Clinical Trials

Etiology

Acute Radiation Enteritis

Diagnosis

Assessment

Medical management

The role of nutrition

Chronic Radiation Enteritis

Diagnosis

Treatment

Prevention

Purpose of This Summary

Reviewers and Updates

Levels of Evidence

Permission to Use This Summary

Disclaimer

Contact Us