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Gastrointestinal complications such as constipation, impaction, bowel obstruction, diarrhea, and radiation enteritis are common problems for patients with cancer. 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.[
Perhaps the most common causes of constipation are inadequate fluid intake and pain medications. 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 also lead to constipation. Many of these contributing conditions are manageable.
Constipation may be annoying and uncomfortable, but fecal impaction can be life-threatening. Impaction is 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.[
In contrast to constipation and 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 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 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. This condition can do the following:
In some cases, diarrhea 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.[
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 in individuals with lung or head and neck cancers who were receiving radiation with or without chemotherapy.[
The large and small bowel are 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.
References:
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 include the following:[
Physiological factors include the following:
Any of these factors can occur because of the disease process, aging, debilitation, or treatment.
Causes of Constipation
*Frequently seen in oncology patients.
Medications
Diet
Altered bowel habits
Prolonged immobility* and/or inadequate exercise
Bowel disorders
Neuromuscular disorders (disruption of innervation leads to atony of the bowel)
Metabolic disorders
Depression
Inability to increase intra-abdominal pressure
Atony of muscles
Environmental factors
Narrowing of colon lumen
Constipation is frequently the result of autonomic neuropathy caused by vinca alkaloids, oxaliplatin, 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 reflex and decreased gut motility. Since constipation is common with the use of opioids, a bowel regimen should be initiated when opioids are prescribed and continued for as long as the patient takes them. 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.[
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.[
Assessment of Constipation
A normal bowel pattern is having at least three stools per week and no more than three stools per day; however, these criteria may be inappropriate for patients with cancer.[
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 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). See 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.[
Assessment
Commonly used interventions
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.
Another approach, shown below in two parts, is adapted from the MD Anderson Cancer Center practice consensus algorithm for the prevention and management of opioid-induced constipation. Copyright 2008 The University of Texas MD Anderson Cancer Center
MD Anderson Cancer Center Algorithm for the Prevention of Opioid-induced Constipation
Unless there are existing alterations in bowel patterns (e.g., bowel obstruction or diarrhea), patients receiving opioids are started on a laxative bowel regimen and receive education for bowel management.
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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.
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 dysmotility of the colon resulting in chronic constipation or fecal incontinence.[
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
Saline laxatives
Stimulant laxatives
Lubricant laxatives
Fecal softeners
Lactulose (Cholac, Cephulac)
Polyethylene glycol and electrolytes (Golytely, Colyte)
Opioid antagonists (naloxone, methylnaltrexone, naldemedine)
Other drugs (lubiprostone, linaclotide, prucalopride)
Lubiprostone
Linaclotide
Prucalopride
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.
References:
Etiology of Impaction
Five major factors that precipitate 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. For causes of constipation that may lead to impaction, see the Etiology of Constipation section.
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, such as urinary retention or increased or decreased frequency or urgency of urination, may develop.
When abdominal distention occurs, movement of the diaphragm may be compromised, which can lead to insufficient aeration with subsequent hypoxia and/or 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 listed previously for the patient with constipation. 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) will 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 electrocardiogram can be performed. If the patient has become dehydrated, the blood levels of urea nitrogen, creatinine, and serum osmolality will be elevated. There may be elevated hemoglobin and hematocrit levels, indicating hemoconcentration. The white blood cell (WBC) count may be slightly higher in the presence of a fever. If the WBC count is extremely elevated and the patient has 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 in that fecal impaction can irritate the bowel wall, and excess enemas 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.[
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.
References:
The four types of obstruction include the following:
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 the following:[
Nonmechanical factors include those that interfere with the muscle action or innervation of the bowel such as the following:
Eighty percent of bowel obstructions occur in the small intestine; the other 20% occur in the colon.[
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.[
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 the location of the obstruction. 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 exhibits 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 to manage 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 reduce edema, relieve fluid and gas accumulation, or decrease the need for multiple stage procedures,[
Management of Chronic, Malignant Bowel Obstruction
Patients with advanced cancer may have chronic, progressive bowel obstruction that is inoperable.[
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.[
When neither surgery nor stenting is possible, the accumulation of the unabsorbed secretions produce nausea, vomiting, pain, and colicky activity as a result 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 accumulate and cause 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. Accumulation of fluid may cause this problem 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) [
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 select 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.[
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.
References:
The reported prevalence and severity of diarrhea in patients with cancer vary greatly. Some chemotherapeutic regimens, particularly those containing fluoropyrimidines or irinotecan, are associated with diarrhea rates as high as 50% to 80%.[
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).[
Grade | Description |
---|---|
ADL = activities of daily living. | |
a Adapted from National Cancer Institute.[ |
|
b Definition: A disorder characterized by an increase in frequency and/or loose or watery bowel movements. | |
c Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. | |
d Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not being 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 ADLc |
3 | Increase of ≥7 stools/day over baseline; hospitalization indicated; severe increase in ostomy output compared with baseline; limiting self-care ADLd |
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.[
Other causes of acute diarrhea include the following:[
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.[
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 mechanisms 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 the following:[
Certain chemotherapeutic agents can alter normal absorption and secretion functions of the small bowel, resulting in treatment-related 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 therapy ends and necessitates dietary modification, pharmacological management, and, in some instances, surgical intervention. For more information, see the Radiation Enteritis section.
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.[
Cancer[ |
Carcinoid syndrome |
Colon cancer | |
Lymphoma | |
Medullary carcinoma of the thyroid | |
Pancreatic cancer, particularly islet cell tumors (Zollinger-Ellison syndrome) | |
Pheochromocytoma | |
Surgery or procedure[ |
Celiac plexus block |
Cholecystectomy, esophagogastrectomy | |
Gastrectomy, pancreaticoduodenectomy (Whipple procedure) | |
Intestinal resection (malabsorption due to short bowel syndrome) | |
Vagotomy | |
Chemotherapy[ |
Capecitabine, cisplatin, cytosine arabinoside, cyclophosphamide, daunorubicin, docetaxel, doxorubicin, 5-fluorouracil, interferon, irinotecan, leucovorin, methotrexate, oxaliplatin, paclitaxel, topotecan, lapatinib, pertuzumab |
Radiation therapy (For more information, see the Radiation Enteritissection.)[ |
Irradiation to the abdomen, para-aortics, lumbar, and pelvis or radiation for lung and head and neck cancers |
Bone marrow transplantation[ |
Conditioning chemotherapy, total-body irradiation, graft-versus-host disease after allogeneic bone marrow or peripheral blood stem cell transplants |
Drug adverse effects[ |
Antibiotics, magnesium-containing antacids, antihypertensives, colchicine, digoxin, lactulose, laxatives, methyldopa, metoclopramide, misoprostol, potassium supplements, propranolol, theophylline |
Concurrent disease[ |
Diabetes, hyperthyroidism, inflammatory bowel disease (Crohn disease, diverticulitis, gastroenteritis, HIV/AIDS, ulcerative colitis), obstruction (tumor related) |
Infection[ |
Clostridium difficile, Clostridium perfringens, Bacillus cereus, Giardia lamblia, Cryptosporidium, Salmonella, Shigella, Campylobacter, Rotavirus |
Fecal impaction[ |
Constipation leading to obstruction |
Diet[ |
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[ |
Stress |
Assessment of Diarrhea
Rapid yet thorough assessment of diarrhea is imperative because of its potentially life-threatening nature. Few standardized assessment tools are available, and as a result, standardized assessment is rare in the clinical setting.[
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.[
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.[
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.[
The time course of diarrhea and concomitant symptom development are key to determining underlying etiology.[
Adverse Event | Grade | Description |
---|---|---|
IV = intravenous; TPN = total parenteral nutrition. | ||
a Adapted from National Cancer Institute.[ |
||
b Definition: A disorder characterized by a queasy sensation and/or the urge to vomit. | ||
c Definition: A disorder characterized by the reflexive act of ejecting the contents of the stomach through the mouth. | ||
Nauseab | 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 | |
Vomitingc | 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.[
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.
Management of Diarrhea
A review was conducted of early toxic deaths in two NCI-sponsored cooperative trials of irinotecan plus high-dose fluorouracil and leucovorin for advanced colorectal cancer. It led to the revision of 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.[
Uncomplicated symptoms
The 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.[
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).[
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 did not show any benefit.[
The goals of pharmacological 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, but little data support their efficacy. Some patients may not tolerate these bulk-forming agents 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.[
Mucosal prostaglandin inhibitors, also referred to as antisecretory agents, include the following:
Other pharmacological 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 addition to antidiarrheal agents and immunosuppressive medications, a specialized, five-phase dietary regimen may be instituted to effectively manage diarrhea associated with GVHD.[
Probiotics
Probiotics are nutritional supplements that contain a defined amount of viable microorganisms and, upon administration, confer a benefit to the patient.[
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.[
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.[
Octreotide, a somatostatin analogue, 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.[
Several open-label and randomized controlled studies of octreotide for chemotherapy-induced diarrhea have demonstrated the efficacy of this therapy.[
An expert panel recommended using high-dose loperamide (2 mg q2h) for the first day of chemotherapy-induced, low-grade diarrhea (grade 1 or 2), followed by octreotide (100 µg–150 µg q8h).[
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 responds well to atropine. Delayed diarrhea, however, is typically managed with antidiarrheals and other supportive measures, as outlined above.[
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.[
Phosphatidylinositol 3-kinase (PI3K) inhibitors
The U.S. Food and Drug Administration has approved four PI3K inhibitors, two of which (idelalisib and duvelisib) carry a boxed warning for gastrointestinal complications, including diarrhea.[
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.
References:
Etiology of Radiation Enteritis
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.[
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 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.[
Acute enteritis symptoms usually resolve 2 to 3 weeks after the completion of treatment, and the mucosa may appear nearly normal.[
Assessment
Patient examination and assessment of radiation enteritis includes the following:[
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:
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 have 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.[
Foods to avoid
Foods to encourage
Helpful hints
Chronic Radiation Enteritis
Diagnosis
Only 5% to 15% of patients who receive abdominal or pelvic irradiation develop chronic radiation enteritis. Signs and symptoms include the following:
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. Radiological findings include submucosal thickening, single or multiple stenoses, adhesions, and sinus or fistula formation.[
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 to 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.[
The timing and choice of surgical techniques remain somewhat controversial. A lower operative mortality (21% vs. 10%) and incidence of anatomic dehiscence (36% vs. 6%) have been reported with intestinal bypass compared with resection.[
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 share of patients.[
Prevention
Treatment techniques that can minimize the risk of severe radiation enteritis include the following:
References:
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Constipation
Added text about three drugs used to treat constipation: lubiprostone, linaclotide, and prucalopride (cited Davies et al. as reference 16 and Thayalasekeran et al. as reference 17).
Diarrhea
Updated National Comprehensive Cancer Network as reference 64.
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.
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 in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
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).
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.
The lead reviewers for Gastrointestinal Complications are:
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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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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Last Revised: 2022-08-02
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