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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. 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. If the fecal impaction is not recognized, the signs and symptoms may progress and result in death.
In contrast to constipation or impaction, an intestinal obstruction is a partial or complete occlusion of the bowel lumen by a process other than fecal impaction. Intestinal obstructions can be classified by three means: the type of obstruction, the obstructing mechanism, and the part of the bowel involved.
Structural disorders, such as intraluminal and extraluminal bowel lesions caused by primary or metastatic tumor, postoperative adhesions, volvulus of the bowel, or incarcerated hernia, affect peristalsis and the maintenance of normal bowel function. These disorders can lead to total or partial obstruction of the bowel. Patients who have colostomies are at special risk of developing constipation. If stool is not passed on a regular basis (once a day to several times a day), further investigation is warranted. A partial or complete blockage may have occurred, particularly if no flatus has been passed.
Diarrhea can occur throughout the continuum of cancer care, and the effects can be physically and emotionally devastating. Although less prevalent than constipation, diarrhea remains a significant symptom burden for people with cancer. Diarrhea can alter dietary patterns, trigger dehydration, create electrolyte imbalance, impair function, cause fatigue, impair skin integrity, limit activity, and in some cases, be life-threatening. Furthermore, diarrhea can lead to increased caregiver burden. Specific definitions of diarrhea vary widely. Acute diarrhea is generally considered to be an abnormal increase in stool liquid that lasts more than 4 days but less than 2 weeks. Another definition suggests that diarrhea is an increase in stool liquidity (>300 mL of stool) and frequency (the passage of more than three unformed stools) during a 24-hour period. Diarrhea is considered chronic when it persists longer than 2 months.
Radiation enteritis is a functional disorder of the large and small bowel that occurs during or after a course of radiation therapy to the abdomen, pelvis, or rectum.
The large and small bowel are very sensitive to ionizing radiation. Although the probability of tumor control increases with the radiation dose, so does the damage to normal tissues. Acute side effects to the intestines occur at approximately 10 Gy. Because curative doses for many abdominal or pelvic tumors range between 50 and 75 Gy, enteritis is likely to occur.
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.
Etiology of Constipation
Common factors that contribute to the development of constipation in the general population are diet, altered bowel habits, inadequate fluid intake, and lack of exercise. Constipation can be a presenting symptom of cancer, or it can occur later as a side effect of a growing tumor or treatment of the tumor. For patients with cancer, additional causative factors are the tumor itself, cancer-related problems, the effects of drug therapy for cancer or for cancer pain, and other concurrent processes such as organ failure, decreased mobility, and depression. Physiologic factors include inadequate oral intake, dehydration, inadequate intake of dietary fiber, or organ failure. Any or all of these factors can occur because of the disease process, aging, debilitation, or treatment. (Refer to the Nausea, Vomiting, Constipation, and Bowel Obstruction in Advanced Cancer section in the PDQ summary on Nausea and Vomiting for more information.)
Causes of Constipation
Altered bowel habits
Prolonged immobility* and/or inadequate exercise
Neuromuscular disorders (disruption of innervation leads to atony of the bowel)
Inability to increase intra-abdominal pressure
Atony of muscles
Narrowing of colon lumen
*Frequently seen in oncology patients.
Constipation is frequently the result of autonomic neuropathy caused by the vinca alkaloids, taxanes, and thalidomide. Other drugs such as opioid analgesics or anticholinergics (antidepressants and antihistamines) may lead to constipation by causing decreased sensitivity to the defecation reflexes and decreased gut motility. Since constipation is common with the use of opioids, a bowel regimen should be initiated at the time opioids are prescribed and continued for as long as the patient takes opioids. Opioids produce varying degrees of constipation, suggesting a dose-related phenomenon. One study suggests that clinicians should not base laxative prescribing on the opioid dose, but rather should titrate the laxative according to bowel function. Lower doses of opioids or weaker opioids, such as codeine, are just as likely to cause constipation. (Refer to the Side Effects of Opioids section in the PDQ summary on Pain for more information.)
Other diseases, such as diabetes (with autonomic neuropathy) and hypothyroidism, may cause constipation. Metabolic disorders, such as hypokalemia and hypercalcemia, also predispose cancer patients to developing constipation. Once these disorders are corrected, constipation should subside.
Assessment of Constipation
A normal bowel pattern is having at least three stools per week and no more than three per day; however, these criteria may be inappropriate for cancer patients.[1,3] Constipation should be viewed as a subjective symptom involving the complaints of decreased frequency with incomplete passage of dry, hard stool. A thorough history of the patient's bowel pattern, dietary changes, and medications, along with a physical examination, can identify possible causes of constipation. The evaluation should also include assessment of associated symptoms such as distention, flatus, cramping, or rectal fullness. A digital rectal examination should always be done to rule out fecal impaction at the level of the rectum. A test for occult blood will be helpful in determining a possible intraluminal lesion. A thorough examination of the gastrointestinal tract is necessary if cancer is suspected.
The following questions may provide a useful assessment guide:
Physical assessment will determine the presence or absence of bowel sounds, flatus, or abdominal distention. Patients with colostomies should also be assessed for constipation. Dietary habits, fluid intake, activity levels, and use of opioids in these patients should be assessed. Irrigation of the colostomy should be monitored for proper technique.
Management of Constipation
Comprehensive management of constipation includes prevention (if possible), elimination of causative factors, and judicious use of laxatives. Some patients can be encouraged to increase dietary fiber (fruits; green, leafy vegetables; 100% whole-grain cereals and breads; and bran) and to increase fluid intake to one-half ounce per pound of body weight daily (if not contraindicated by renal or heart disease). (Refer to the PDQ summary on Nutrition in Cancer Care for more information.) A study that involved geriatric patients compared the efficacy, cost, and ease of administration of a natural laxative mixture (raisins, currants, prunes, figs, dates, and prune concentrate) with protocols using stool softeners, lactulose, and other laxatives. Results 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. A program for prevention of constipation in cancer patients is described below.
Commonly used interventions:
While there are no specific fiber recommendations for cancer patients, they should also be encouraged to eat more high-fiber foods such as fruits (e.g., raisins, prunes, peaches, and apples), vegetables (e.g., squash, broccoli, carrots, and celery), and 100% whole-grain cereals, breads, and bran. Increased fiber intake must be accompanied by increased fluid intake, or constipation may result. High fiber intake is contraindicated in patients at increased risk for bowel obstruction, such as those with a history of bowel obstruction or status postcolostomy.
Another approach, shown below in two parts, is adapted from the MD Anderson Cancer Center practice consensus algorithm for the prevention and management of opioid-induced constipation. Copyright 2008 The University of Texas MD Anderson Cancer Center
MD Anderson Cancer Center Algorithm for the Prevention of Opioid-induced Constipation
MD Anderson Cancer Center Algorithm for the Management of Opioid-induced Constipation
Medical management includes the administration of saline or chemical laxatives, suppositories, enemas, or agents that increase bulk.
Rectal agents should be avoided in cancer patients at risk for thrombocytopenia, leukopenia, and/or mucositis from cancer and its treatment. In the immunocompromised patient, no manipulation of the anus should occur, that is, no rectal examinations, no suppositories, and no enemas. These actions can lead to the development of anal fissures or abscesses, which are portals of entry for infection. Also, the stoma of a patient with neutropenia should not be manipulated.
Medical Agents for Constipation
Lactulose (Cholac, Cephulac)
Polyethylene glycol and electrolytes (Golytely, Colyte)
Opioid antagonists (naloxone, methylnaltrexone)
Current Clinical Trials
Check NCI's list of cancer clinical trials for U.S. supportive and palliative care trials about constipation, impaction, and bowel obstruction that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Etiology of Impaction
Five major factors precipitate impaction:
Laxatives used to decrease constipation are the drugs that contribute most to the development of constipation and impaction. Repeated and escalating dosing of laxatives renders the colon less sensitive to its intrinsic reflexes stimulated by distention. (Refer to the Etiology of Constipation section of this summary for causes of constipation that may lead to impaction.)
Signs and Symptoms of Impaction
The patient may exhibit symptoms similar to constipation or present with symptoms unrelated to the gastrointestinal system. If the impaction presses on the sacral nerves, the patient may experience back pain. If the impaction presses on the ureters, bladder, or urethra, urinary symptoms can develop. These symptoms include increased or decreased frequency or urgency of urination, or urinary retention.
When abdominal distention occurs, movement of the diaphragm is compromised, leading to insufficient aeration with subsequent hypoxia and left ventricular dysfunction. Hypoxia can, in turn, precipitate angina or tachycardia. If the vasovagal response is stimulated by the pressure of impaction, the patient may become dizzy and hypotensive.
Movement of stool around the impaction may result in diarrhea, which can be explosive. Coughing or activities that increase intra-abdominal pressure may cause leakage of stool. The leakage may be accompanied by nausea, vomiting, abdominal pain, and dehydration and is virtually diagnostic of the condition. Thus, the patient with an impaction may present in an acutely confused and disoriented state, with signs of tachycardia, diaphoresis, fever, elevated or low blood pressure, and/or abdominal fullness or rigidity.
Assessment of Impaction
Assessment includes the questions discussed previously for the patient with constipation. (Refer to the Assessment of Constipation section of this summary for the list of questions.) Additional assessment includes auscultation of bowel sounds to determine if they are present, absent, hyperactive, or hypoactive. The abdomen should be inspected for distention and gently palpated for any masses, rigidity, or tenderness. A rectal examination will determine the presence of stool in the rectum or sigmoid colon. An abdominal x-ray (flat and upright) would show loss of haustral markings, gas patterns reflecting gross amounts of stool, and dilatation proximal to the impaction.
If a diagnosis of fecal impaction is uncertain, a laboratory workup can rule out other problems. A complete blood cell count, appropriate blood chemistries, chest x-ray, and an electrocardiogram can be performed. If the patient has become dehydrated, the blood urea nitrogen, creatinine, and serum osmolality will be elevated. There may be an elevation of the hemoglobin and hematocrit indicating hemoconcentration. The white blood cell (WBC) count may be slightly elevated in the presence of a fever. If the WBC count is extremely elevated and the patient is exhibiting a high fever and abdominal pain, an obstruction, perforation, infection, or inflammatory process must be ruled out. With marked distention of the cecum (diameter ≥12 cm), there is a risk of bowel perforation.
Treatment of Impaction
The primary treatment of impaction is to hydrate and soften the stool so that it can be removed or passed. Enemas (oil retention, tap water, or hypertonic phosphate) lubricate the bowel and soften the stool. Caution must be exercised; fecal impaction can irritate the bowel wall, and enemas in excess may perforate the bowel. The patient may need to be digitally disimpacted if the stool is within reach. This is best done after administering an enema to lubricate the bowel.
Nonstimulating bowel softeners such as docusate can be used to help soften stool higher in the colon. Mineral or olive oil can be given to loosen the stool. Caution should be used when giving docusate sodium with mineral oil because there could be an increased systemic absorption of the mineral oil leading to systemic lipid granulomas. Glycerin suppositories can also be used. Any laxatives that might stimulate the bowel or cause cramping should be avoided so that the bowel is not damaged further.
There are four types of obstruction:
A simple obstruction is blocked in one place; a closed-loop obstruction is blocked in two places. A closed-loop obstruction may develop when the bowel twists around on itself, isolating the looped section of the bowel and obstructing the portion above it. With a strangulated obstruction, there is decreased blood flow to the bowel that, if not relieved, will develop into an incarcerated obstruction, and the bowel will become necrotic.
The obstructing mechanism can be mechanical or nonmechanical. Mechanical factors can be anything that causes a narrowing of the intestinal lumen (e.g., inflammation or trauma to the bowel, neoplasms, adhesions, hernias, volvulus, or a compression from outside the intestinal tract). Nonmechanical factors include those that interfere with the muscle action or innervation of the bowel: paralytic ileus, mesenteric embolus or thrombus, and hypokalemia.
Eighty percent of bowel obstructions occur in the small intestine; the other 20% occur in the colon. 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. Patients who have had abdominal surgery or abdominal radiation are also at higher risk of developing bowel obstruction. Bowel obstructions are most common during advanced stages of disease.
Assessment and Diagnosis of Bowel Obstruction
Examination of the patient will determine the presence or absence of abdominal pain, vomiting, and evidence of the passage of flatus or stool. A complete blood cell count, electrolyte panel, and urinalysis are obtained to evaluate fluid and electrolyte imbalance and/or sepsis. An elevated white blood cell count (15,000–20,000/mm3) suggests bowel necrosis. Flat and upright abdominal films as well as a barium enema may be necessary to determine where the obstruction is located. While it remains controversial, an upper gastrointestinal series is contraindicated with an acutely presenting obstruction because it can cause a partial obstruction to become complete or may further complicate a total obstruction. If the patient is exhibiting dehydration, oliguria, or shock, perforation of the bowel may have occurred, and immediate medical or surgical intervention is indicated. (Refer to the Nausea, Vomiting, Constipation, and Bowel Obstruction in Advanced Cancer section in the PDQ summary on Nausea and Vomiting for more information.)
Treatment of Acute Bowel Obstruction
Careful serial examinations are necessary in the management of patients with progressive abdominal symptoms that may be due to acute bowel obstruction. The principles of supportive care in this setting include volume resuscitation, correction of electrolyte imbalances, and transfusion support (if necessary). These measures should precede or accompany decompression efforts.
When bowel obstruction is partial, decompression of the distended bowel may be attempted with nasogastric or intestinal tubes. Although use of these tubes may be successful in reducing edema, relieving fluid and gas accumulation, or decreasing the need for multiple stage procedures, 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.
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] 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.
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].
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)  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] 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. They may be useful as adjuvant antiemetics and analgesics in this setting, given as dexamethasone at a starting dose of 6 to 10 mg subcutaneously or intravenously 3 to 4 times per day.[12,25] (Refer to the Nausea, Vomiting, Constipation, and Bowel Obstruction in Advanced Cancer section in the PDQ summary on Nausea and Vomiting for more information.)
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. In a large heterogeneous sample of cancer patients in various stages of treatment, the prevalence of moderate-to-severe diarrhea was 14%. Diarrhea occurs in approximately 7% to 10% of cancer patients upon admission to hospice. Among children with cancer during the last month of life, 19% experienced diarrhea.
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 (see Table 1).[7,8] A review of several clinical trials of irinotecan plus high-dose fluorouracil and leucovorin in colorectal cancer revealed early death rates of 2.2% to 4.8%, primarily due to gastrointestinal toxicity. 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.
Etiology of Diarrhea
In patients being treated for cancer, diarrhea is most commonly induced by therapy. Conventional methods of diarrhea-causing treatment include surgery, chemotherapy, radiation therapy, and bone marrow transplantation. Other causes of acute diarrhea include antibiotic therapy, stress and anxiety associated with cancer diagnosis and treatment, and infection. 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.Clostridium difficile is a common cause of pseudomembranous colitis. Other causes of diarrhea in patients with cancer include the underlying cancer, responses to diet, or concomitant diseases (see Table 2). Common causes of diarrhea in patients receiving palliative care are difficulty adjusting the laxative regimen and impaction leading to leakage of stool around the fecal obstruction.
Another strategy for categorizing the causes of diarrhea is by putative underlying mechanisms. These include exudative (i.e., excess blood or mucous enters the gastrointestinal tract), malabsorptive, dysmotile, osmotic, and secretory (due to increased secretion of electrolytes and fluid—probably the mechanism underlying chemotherapy-induced diarrhea) factors or combinations of these factors.
Surgery, a primary treatment modality for many cancers, can affect the body by mechanical, functional, and physiological alterations. Postsurgical complications of gastrointestinal surgery affecting normal bowel function that may contribute to diarrhea include increased transit time, gastroparesis, fat malabsorption, lactose intolerance, fluid and electrolyte imbalance, and dumping syndrome.[14,15]
Certain chemotherapeutic agents can alter normal absorption and secretion functions of the small bowel, resulting in treatment-related diarrhea. 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 total dose, fractionation, volume of bowel irradiated, and concomitant chemotherapy. Common side effects of intestinal enteritis include diarrhea, malabsorption, gas, bloating, and cramping. Acute intestinal side effects occur at approximately 10 Gy and may last up to 8 to 12 weeks posttherapy. Chronic radiation enteritis may present months to years after completion of therapy and necessitates dietary modification and pharmacological management and, in some instances, surgical intervention. (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. 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. 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.
Because of the potentially life-threatening nature of diarrhea, rapid, yet thorough, assessment is imperative. Few standardized assessment tools are available, and studies suggest that, as a result, standardized assessment is rare in the clinical setting. 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. The NCI's Common Terminology Criteria for Adverse Events (Table 1) evaluate diarrhea by number of stools per day, incontinence, and increase in ostomy output compared to baseline.
The history also should include questions regarding the frequency of bowel movements during the past 24 hours, the character of the fecal material, and the time course of the development of diarrhea. One author has developed a visual tool to assist patients and families in characterizing the consistency of the stool. Six diagrams illustrate fecal material consistency ranging from well-formed, formed, and semiformed to loose, very loose, and liquid. Patients should be questioned regarding related symptoms that might indicate hemodynamic compromise or the underlying etiology. Specifically, questions should include information about dizziness, orthostatic symptoms, lethargy, cramping, abdominal pain, nausea, vomiting, fever, and rectal bleeding. These symptoms should be classified as complicated or uncomplicated, with therapy based on these classifications. Uncomplicated symptoms include grade 1 or 2 diarrhea with no other signs or symptoms. Management is conservative. Complicated symptoms include grade 1 or 2 diarrhea with any one of the following risk factors: moderate to severe cramping, grade 2 or higher nausea/vomiting (see Table 3), decreased performance status, fever, sepsis, neutropenia, frank bleeding, or dehydration. Grade 3 or 4 diarrhea is also classified as complicated. Thorough evaluation and close monitoring is warranted. The time course of diarrhea and concomitant symptom development are key to determining underlying etiology. 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.
The goal of physical examination is to identify potential causes of diarrhea and its complications as quickly as possible to reduce morbidity. The physical examination should include vital signs and evaluation of skin turgor and oral mucosa to assess hemodynamic status and dehydration. Abdominal examination includes evaluation for rebound tenderness, guarding, hypoactive or hyperactive bowel sounds, and stool collection. A rectal exam can rule out fecal impaction but should be performed judiciously in neutropenic or thrombocytopenic patients.
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.
In some cases, radiographic procedures are conducted to identify ileus, obstruction, or other abnormalities. In rare cases, endoscopy may be indicated.
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.
The current treatment of cancer-related diarrhea is often empiric and nonspecific. Whenever possible, treat underlying causes such as fecal impaction or modify the stimulant laxative regimen as necessary. Medications such as bulk laxatives and promotility agents (e.g., metoclopramide) should be discontinued. Dietary modifications are commonly implemented to stop or lessen the severity of cancer treatment-related diarrhea.[7,23,24,29] One author recommends that patients should consume foods that build stool consistency, are low in fiber, contain minerals, and do not stimulate or irritate the gastrointestinal tract. In some cases, dietary modification for diarrhea management includes advising patients to eat small, frequent meals and avoid lactose-containing food (milk and dairy products), spicy foods, alcohol, caffeine-containing foods and beverages, certain fruit juices, gas-forming foods and beverages, high-fiber foods, and high-fat foods. For mild cases of diarrhea, the BRAT (bananas, rice, apples, toast) diet may reduce the frequency of stools. When experiencing diarrhea, patients should be encouraged to increase clear liquid intake to at least 3 L per day (e.g., water, sports drinks, broth, weak decaffeinated teas, caffeine-free soft drinks, clear juices, and gelatin).[12,31] (Refer to the Diarrhea subsection of the Nutritional Suggestions for Symptom Management section in the PDQ summary on Nutrition in Cancer Care for more information.)
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.[Level of evidence: I][33,34]
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. Common loperamide doses begin with 4 mg, followed by 2 mg after each unformed stool with a maximum of approximately 12 mg/day.[5,26] Regardless of the dose, however, loperamide may be less effective in patients with grade 3 or 4 diarrhea.[Level of evidence: I]
Mucosal prostaglandin inhibitors, also referred to as antisecretory agents, include aspirin, bismuth subsalicylate, corticosteroids, and octreotide. Aspirin may be useful for radiation-induced diarrhea. Bismuth subsalicylate is believed to have direct antimicrobial effects on Escherichia coli, hence its prophylactic use in traveler's diarrhea. This agent is contraindicated in patients who should not be taking aspirin, and large doses can produce toxic salicylate levels. Corticosteroids reduce edema associated with obstruction and radiation colitis and can reduce hormonal influences of some endocrine tumors.
Other pharmacologic therapies for the relief of diarrhea may be specific to the underlying mechanism. Delayed diarrhea (>24 hours) occurs with irinotecan and can be severe in 25% of patients. 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.[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 to 32 patients receiving the same chemotherapeutic regimen without oral alkalization and controlled defecation.[Level of evidence: III]
In addition to antidiarrheal agents and immunosuppressive medications, a specialized five-phase dietary regimen should be instituted to effectively manage the diarrhea associated with GVHD. Phase 1 consists of total bowel rest until the diarrhea is reduced. Nitrogen losses associated with diarrhea can be severe and are compounded by the high-dose corticosteroids used to treat GVHD. Phase 2 reintroduces oral feedings consisting of beverages that are isotonic, low-residue, and lactose-free to compensate for the loss of intestinal enzymes secondary to alterations in the intestinal villi and mucosa. If these beverages are well tolerated, phase 3 may reintroduce solids containing minimal lactose, low fiber, low fat, low total acidity, and no gastric irritants. In phase 4, dietary restrictions are progressively reduced as foods are gradually reintroduced and tolerance is established. Phase 5 includes the resumption of the patient's regular diet; however, most patients usually remain lactose intolerant.
Probiotics are nutritional supplements that contain a defined amount of viable microorganisms and, upon administration, confer a benefit to the patient. 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. 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:[41,42,43,44,45,46]
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.
Clinical trials for the following patients are under way:
While the optimal dose of octreotide has not been determined, a panel of experts has recommended that complicated cases of diarrhea should be managed with 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 should be continued until the patient has been diarrhea free for 24 hours. Particularly when patients are receiving chemotherapy, additional evaluation should include stool workup (including blood, fecal leukocytes, C. difficile, Salmonella, E. coli, Campylobacter, and infectious colitis), complete blood count, and electrolyte profile. This workup and treatment should also be considered for patients who progress to grade 3 or 4 diarrhea while taking loperamide. The same panel suggests that severe radiation therapy–induced diarrhea may not require hospitalization (an alternative outpatient unit or intensive home care nursing may be able to provide the same level of care and monitoring) but the patient's constellation of symptoms should be considered to determine the appropriate workup and whether IV fluids or octreotide is indicated.
Octreotide, a somatostatin analog, is currently the most promising agent in the management of severe diarrhea caused by a variety of diseases and treatments. The doses used in clinical trials have varied widely. Regardless of the lack of consensus regarding optimal dose, octreotide has been shown to be effective in relieving diarrhea associated with AIDS, carcinoid syndrome, and vasoactive intestinal polypeptide tumors.[Level of evidence: II] Several open-label and randomized controlled studies of octreotide in the relief of chemotherapy-induced diarrhea have demonstrated the efficacy of this therapy.[49,50,51][Level of evidence: I];[52,53,54][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. Octreotide has also been shown to be effective in diarrhea associated with GVHD.[56,57] An expert panel recommended using high-dose loperamide (2 mg every 2 hours) for the first day of chemotherapy-induced diarrhea that is low grade (1 and 2), followed by octreotide, 100 to 150 µg every 8 hours. If the patient presents with severe diarrhea (grade 3 or 4), octreotide, 500 to 1,500 µg SC or IV every 8 hours, should be first-line therapy. A phase III, double-blind study of depot octreotide for the prevention of diarrhea during pelvic radiation treatment did not demonstrate any benefit. 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.)
Check NCI's list of cancer clinical trials for U.S. supportive and palliative care trials about diarrhea that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.
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. 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.
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
Radiation therapy exerts a cytotoxic effect mainly on rapidly proliferating epithelial cells, like those lining the large and small bowel. Crypt cell wall necrosis can be observed 12 to 24 hours after a daily dose of 1.5 to 3 Gy. Progressive loss of cells, villous atrophy, and cystic crypt dilation occur in the ensuing days and weeks. Patients suffering from acute enteritis may complain of nausea, vomiting, abdominal cramping, tenesmus, and watery diarrhea. With diarrhea, the digestive and absorptive functions of the gastrointestinal (GI) tract are altered or lost, resulting in malabsorption of fat, lactose, bile salts, and vitamin B12. Symptoms of proctitis—including mucoid rectal discharge, rectal pain, and rectal bleeding (if mucosal ulceration is present)—may result from radiation damage to the anus or rectum.
Acute enteritis symptoms usually resolve 2 to 3 weeks after the completion of treatment, and the mucosa may appear nearly normal.
Patient examination and assessment of radiation enteritis should include the following:
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:
In addition to these medications, opioids may offer relief from abdominal pain. If proctitis is present, a steroid foam given rectally may offer relief from symptoms. Finally, if patients with pancreatic cancer are experiencing diarrhea during radiation therapy, they should be evaluated for oral pancreatic enzyme replacement, as deficiencies in these enzymes alone can cause diarrhea.
The role of nutrition
Damage to the intestinal villi from radiation therapy results in a reduction or loss of enzymes, one of the most important of these being lactase. Lactase is essential in the digestion of milk and milk products. Although there is no evidence that a lactose-restricted diet will prevent radiation enteritis, a diet that is lactose free, low fat, and low residue can be an effective modality in symptom management.[Level of evidence: I]
Foods to avoid
Foods to encourage
Chronic Radiation Enteritis
Only 5% to 15% of the patients who receive abdominal or pelvic irradiation will develop chronic radiation enteritis. Signs and symptoms include colicky abdominal pain, bloody diarrhea, tenesmus, steatorrhea, weight loss, and nausea and vomiting. Less common are bowel obstruction, fistulas, bowel perforation, and massive rectal bleeding. 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. 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.
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.[Level of evidence: I] Fewer than 2% of the 5% to 15% of patients who received abdominal or pelvic radiation will require surgical intervention.
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.[Level of evidence: II] 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. All agree that simple lysis of adhesions is inadequate and that fistulas require bypass.
Surgery should be undertaken only after careful assessment of the patient's clinical condition and extent of radiation damage because wound healing is often delayed, necessitating prolonged parenteral feeding after surgery. Even after apparently successful operations, symptoms may persist in a significant proportion of patients.
Treatment techniques that can minimize the risk of severe radiation enteritis include the following:
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Purpose of This Summary
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.
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National Cancer Institute: PDQ® Gastrointestinal Complications. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/supportivecare/gastrointestinalcomplications/HealthProfessional. Accessed <MM/DD/YYYY>.
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Last Revised: 2012-07-18
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