Gastrointestinal Complications (PDQ®)

References

1. Larkin PJ, Cherny NI, La Carpia D, et al.: Diagnosis, assessment and management of constipation in advanced cancer: ESMO Clinical Practice Guidelines. Ann Oncol 29 (Suppl 4): iv111-iv125, 2018. [PubMed: 30016389]
2. Hussain ZH, Whitehead DA, Lacy BE: Fecal impaction. Curr Gastroenterol Rep 16 (9): 404, 2014. [PubMed: 25119877]
3. Moschen AR, Sammy Y, Marjenberg Z, et al.: The Underestimated and Overlooked Burden of Diarrhea and Constipation in Cancer Patients. Curr Oncol Rep 24 (7): 861-874, 2022. [PubMed: 35325401]
4. Sonis S, Elting L, Keefe D, et al.: Unanticipated frequency and consequences of regimen-related diarrhea in patients being treated with radiation or chemoradiation regimens for cancers of the head and neck or lung. Support Care Cancer 23 (2): 433-9, 2015. [PubMed: 25123194]

Causes of Constipation

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, other causative factors include the following:[1,2]

• Medications (e.g., chemotherapy drugs, opioids, antacids, diuretics).
• Diet (inadequate fluid intake, inadequate intake of dietary fiber, decreased appetite).
• Prolonged immobility and/or inadequate exercise.
• Bowel disorders (e.g., inflammatory bowel disease, diverticulitis).
• Neuromuscular disorders (disruption of innervation leading to atony of the bowel, spinal cord injury or compression).
• Metabolic disorders (e.g., dehydration, hypercalcemia, hypokalemia, uremia).
• Depression.
• Environmental factors (lack of privacy, change in bathroom habits, assistance to get to the bathroom).

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

Constipation is frequently the result of autonomic neuropathy caused by vinca alkaloids, oxaliplatin, taxanes, and thalidomide. Other drugs, such as opioid analgesics and anticholinergics (including antidepressants and antihistamines), may lead to constipation by causing decreased sensitivity to the defecation reflex and decreased gut motility. Because 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 suggested that clinicians should not prescribe laxatives based 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 as higher doses and stronger opioids.[3] For more information about opioid-induced constipation, see the Constipation section in Cancer Pain.

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.[4,5]

The following questions may provide a useful assessment guide:

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

A thorough history of the patient’s bowel pattern, dietary changes, and medications, along with a physical examination, can identify possible causes of constipation. The evaluation also includes assessment of associated symptoms such as distention, flatus, cramping, or rectal fullness. The following tests may be part of the clinical evaluation:[6]

• Digital rectal exam: Done to rule out fecal impaction at the level of the rectum.
• Fecal occult blood test: Helpful in determining a possible intraluminal lesion.
• Colonoscopy or sigmoidoscopy: Necessary if cancer is suspected.

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 drink eight 8-oz. (240-mL) glasses of fluid daily unless contraindicated. For more information, see Nutrition in Cancer Care.

Medical agents for constipation

There are different medical agents used to treat constipation. Table 1 lists these agents in more detail.

Table

Table 1. Medical Agents for Constipation.

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

1. Lindberg G, Hamid SS, Malfertheiner P, et al.: World Gastroenterology Organisation global guideline: Constipation--a global perspective. J Clin Gastroenterol 45 (6): 483-7, 2011. [PubMed: 21666546]
2. Davies A, Leach C, Caponero R, et al.: MASCC recommendations on the management of constipation in patients with advanced cancer. Support Care Cancer 28 (1): 23-33, 2020. [PubMed: 31396746]
3. Bennett M, Cresswell H: Factors influencing constipation in advanced cancer patients: a prospective study of opioid dose, dantron dose and physical functioning. Palliat Med 17 (5): 418-22, 2003. [PubMed: 12882260]
4. Portenoy RK: Constipation in the cancer patient: causes and management. Med Clin North Am 71 (2): 303-11, 1987. [PubMed: 3029525]
5. McShane RE, McLane AM: Constipation. Consensual and empirical validation. Nurs Clin North Am 20 (4): 801-8, 1985. [PubMed: 3852308]
6. Bruera E, Suarez-Almazor M, Velasco A, et al.: The assessment of constipation in terminal cancer patients admitted to a palliative care unit: a retrospective review. J Pain Symptom Manage 9 (8): 515-9, 1994. [PubMed: 7531736]
7. Mekhael M, Kristensen HØ, Larsen HM, et al.: Transanal Irrigation for Neurogenic Bowel Disease, Low Anterior Resection Syndrome, Faecal Incontinence and Chronic Constipation: A Systematic Review. J Clin Med 10 (4): , 2021. [PMC free article: PMC7918662] [PubMed: 33668658]
8. Thomas J, Karver S, Cooney GA, et al.: Methylnaltrexone for opioid-induced constipation in advanced illness. N Engl J Med 358 (22): 2332-43, 2008. [PubMed: 18509120]
9. Portenoy RK, Thomas J, Moehl Boatwright ML, et al.: Subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients with advanced illness: a double-blind, randomized, parallel group, dose-ranging study. J Pain Symptom Manage 35 (5): 458-68, 2008. [PubMed: 18440447]
10. Meissner W, Leyendecker P, Mueller-Lissner S, et al.: A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation. Eur J Pain 13 (1): 56-64, 2009. [PubMed: 18762438]
11. Katakami N, Harada T, Murata T, et al.: Randomized Phase III and Extension Studies of Naldemedine in Patients With Opioid-Induced Constipation and Cancer. J Clin Oncol 35 (34): 3859-3866, 2017. [PubMed: 28968171]
12. Thayalasekeran S, Ali H, Tsai HH: Novel therapies for constipation. World J Gastroenterol 19 (45): 8247-51, 2013. [PMC free article: PMC3857447] [PubMed: 24363515]

Causes of Fecal Impaction

Constipation, if left untreated, may lead to fecal impaction. The causes of impaction are the same as the causes of constipation.[1] For more information, see the Causes of Constipation section.

Signs and Symptoms of Fecal Impaction

The patient may exhibit symptoms similar to those of constipation or present with symptoms unrelated to the gastrointestinal system. If the fecal 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. 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 Fecal Impaction

Assessment of fecal impaction includes the same questions as 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.[2] For more information, see the Assessment of Constipation section.

Treatment of Fecal 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.

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

1. Davies A, Leach C, Caponero R, et al.: MASCC recommendations on the management of constipation in patients with advanced cancer. Support Care Cancer 28 (1): 23-33, 2020. [PubMed: 31396746]
2. Bruera E, Suarez-Almazor M, Velasco A, et al.: The assessment of constipation in terminal cancer patients admitted to a palliative care unit: a retrospective review. J Pain Symptom Manage 9 (8): 515-9, 1994. [PubMed: 7531736]

Causes of Bowel Obstruction

The obstructing mechanism can be extrinsic or intrinsic.[1]

Extrinsic causes include the following:

• Inflammation or trauma to the bowel.
• Neoplasms.
• Adhesions.
• Hernias.
• Volvulus.
• Compression from outside the intestinal tract.

Intrinsic causes include the following:

• Paralytic ileus.
• Mesenteric embolus or thrombus.
• Tumor infiltration of the mesentery, bowel muscle, or celiac and enteric plexuses.[2]
• Endometriosis.

Bowel obstructions are more common in the small intestine than in the colon.[3] Bowel obstructions are frequently seen in the ileum. Small bowel obstructions are often caused by adhesions or hernias, while large bowel obstructions are usually caused by carcinomas, volvulus, or diverticulitis. The presentation of obstruction will relate to whether the small or large intestine is involved.

The most common malignancies that cause bowel obstruction are cancers of the colon, stomach, and ovary.[3] 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

Possible symptoms of malignant bowel obstruction include abdominal pain, cramps, distention, nausea, vomiting, absence of gas and stool passage, and, rarely, overflow diarrhea.[3] 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.

Traditionally, flat and upright abdominal films have been used for diagnosis. However, x-rays have only modest sensitivity to detect a bowel obstruction and limited ability to detect the exact site, cause, or complications. Contrast computed tomography (CT) delivers enhanced diagnostic precision. A CT of the abdomen and pelvis with intravenous contrast and/or a CT enterography may be used to diagnose patients suspected of having a small bowel obstruction.[4,5]

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 bowel rest, 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 tubes (NGTs) or intestinal tubes. The use of these tubes may reduce edema, relieve fluid and gas accumulation, or decrease the need for multiple stage procedures.[6] However, 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. The stents permit staging of the disease, increase the rate of primary anastomosis relative to colostomy, and decrease morbidity in patients with left-sided colon and rectal malignancies. Further study is warranted, including cost analysis.[7]

Management of Chronic, Malignant Bowel Obstruction

Patients with advanced cancer may have chronic, progressive bowel obstruction that is inoperable.[8,9] The most frequent causes of inoperability are extensive tumor and multiple partial obstructions.[10,11][Level of evidence: II][12] A retrospective review evaluated surgical palliation of malignant bowel obstruction secondary to peritoneal carcinomatosis in 63 patients with nongynecological cancers. The ability to tolerate solid food at hospital discharge was 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%. The postoperative mortality rate was 15%, and postoperative complications occurred in 44% of patients.[13]

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.[7,14-19] They 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.[20,21][Level of evidence: II][22]

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, temporary decompression may be accomplished using an NGT; however, NGTs are not favored as a long-term solution.[3] Instead, 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 interfere with decompression because several liters of gastrointestinal secretions may be produced per day. Pharmacological symptom management may be necessary. In the case of complete obstruction, avoid oral administration of medications if possible. To relieve continuous abdominal pain, opioid analgesics may be necessary. Associated nausea and vomiting may be treated with several different medications, including scopolamine, octreotide, dexamethasone, haloperidol, metoclopramide, dimenhydrinate, prochlorperazine, serotonin antagonists, and olanzapine.[3] Effective antispasmodics in this situation include anticholinergics (such as scopolamine) [23] and possibly corticosteroids, as well as centrally acting agents.

Careful use of laxatives may be considered for constipation associated with partial bowel obstruction. However, a 2022 systematic review did not identify any studies that examined laxatives in this setting.[3] Osmotic laxatives, such as polyethylene glycol 3350, pull water into the lumen of the bowel, softening stool and increasing peristalsis. Bulk-forming laxatives such as psyllium should be avoided because they increase stool volume and can worsen the obstruction. Finally, manual disimpaction may be necessary if fecal impaction is noted during physical examination.

Another option for management of refractory pain and/or nausea is the synthetic somatostatin analogue octreotide. This agent inhibits the release of several gastrointestinal hormones and reduces gastrointestinal secretions.[24,25][Level of evidence: I][26]

Octreotide is usually given subcutaneously at 50 to 200 µg three times per day and may reduce the nausea, vomiting, and abdominal pain of malignant bowel obstruction. For select patients in whom octreotide alone is ineffective, the addition of an anticholinergic such as scopolamine may help reduce the associated painful colic of malignant bowel obstruction. When either scopolamine or octreotide is used alone, each is ineffective.[14,27-29] Corticosteroids are widely used to treat bowel obstruction, but empirical support is limited.[30]

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

1. Rami Reddy SR, Cappell MS: A Systematic Review of the Clinical Presentation, Diagnosis, and Treatment of Small Bowel Obstruction. Curr Gastroenterol Rep 19 (6): 28, 2017. [PubMed: 28439845]
2. Cousins SE, Tempest E, Feuer DJ: Surgery for the resolution of symptoms in malignant bowel obstruction in advanced gynaecological and gastrointestinal cancer. Cochrane Database Syst Rev (1): CD002764, 2016. [PMC free article: PMC7101053] [PubMed: 26727399]
3. Madariaga A, Lau J, Ghoshal A, et al.: MASCC multidisciplinary evidence-based recommendations for the management of malignant bowel obstruction in advanced cancer. Support Care Cancer 30 (6): 4711-4728, 2022. [PMC free article: PMC9046338] [PubMed: 35274188]
4. Lee YC, Jivraj N, O'Brien C, et al.: Malignant Bowel Obstruction in Advanced Gynecologic Cancers: An Updated Review from a Multidisciplinary Perspective. Obstet Gynecol Int 2018: 1867238, 2018. [PMC free article: PMC5985138] [PubMed: 29887891]
5. Chang KJ, Marin D, Kim DH, et al.: ACR Appropriateness Criteria® Suspected Small-Bowel Obstruction. J Am Coll Radiol 17 (5S): S305-S314, 2020. [PubMed: 32370974]
6. Horiuchi A, Maeyama H, Ochi Y, et al.: Usefulness of Dennis Colorectal Tube in endoscopic decompression of acute, malignant colonic obstruction. Gastrointest Endosc 54 (2): 229-32, 2001. [PubMed: 11474399]
7. Martinez-Santos C, Lobato RF, Fradejas JM, et al.: Self-expandable stent before elective surgery vs. emergency surgery for the treatment of malignant colorectal obstructions: comparison of primary anastomosis and morbidity rates. Dis Colon Rectum 45 (3): 401-6, 2002. [PubMed: 12068202]
8. Ripamonti C, Bruera E: Palliative management of malignant bowel obstruction. Int J Gynecol Cancer 12 (2): 135-43, 2002 Mar-Apr. [PubMed: 11975672]
9. Potluri V, Zhukovsky DS: Recent advances in malignant bowel obstruction: an interface of old and new. Curr Pain Headache Rep 7 (4): 270-8, 2003. [PubMed: 12828876]
10. Jung GS, Song HY, Kang SG, et al.: Malignant gastroduodenal obstructions: treatment by means of a covered expandable metallic stent-initial experience. Radiology 216 (3): 758-63, 2000. [PubMed: 10966707]
11. Camúñez F, Echenagusia A, Simó G, et al.: Malignant colorectal obstruction treated by means of self-expanding metallic stents: effectiveness before surgery and in palliation. Radiology 216 (2): 492-7, 2000. [PubMed: 10924576]
12. Coco C, Cogliandolo S, Riccioni ME, et al.: Use of a self-expanding stent in the palliation of rectal cancer recurrences. A report of three cases. Surg Endosc 14 (8): 708-11, 2000. [PubMed: 10954814]
13. Blair SL, Chu DZ, Schwarz RE: Outcome of palliative operations for malignant bowel obstruction in patients with peritoneal carcinomatosis from nongynecological cancer. Ann Surg Oncol 8 (8): 632-7, 2001. [PubMed: 11569777]
14. Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001. [PubMed: 11386268]
15. Law WL, Chu KW, Ho JW, et al.: Self-expanding metallic stent in the treatment of colonic obstruction caused by advanced malignancies. Dis Colon Rectum 43 (11): 1522-7, 2000. [PubMed: 11089586]
16. Repici A, Reggio D, De Angelis C, et al.: Covered metal stents for management of inoperable malignant colorectal strictures. Gastrointest Endosc 52 (6): 735-40, 2000. [PubMed: 11115905]
17. Harris GJ, Senagore AJ, Lavery IC, et al.: The management of neoplastic colorectal obstruction with colonic endolumenal stenting devices. Am J Surg 181 (6): 499-506, 2001. [PubMed: 11513773]
18. Aviv RI, Shyamalan G, Watkinson A, et al.: Radiological palliation of malignant colonic obstruction. Clin Radiol 57 (5): 347-51, 2002. [PubMed: 12014929]
19. Dauphine CE, Tan P, Beart RW, et al.: Placement of self-expanding metal stents for acute malignant large-bowel obstruction: a collective review. Ann Surg Oncol 9 (6): 574-9, 2002. [PubMed: 12095974]
20. Lopera JE, Alvarez O, Castaño R, et al.: Initial experience with Song's covered duodenal stent in the treatment of malignant gastroduodenal obstruction. J Vasc Interv Radiol 12 (11): 1297-303, 2001. [PubMed: 11698629]
21. Razzaq R, Laasch HU, England R, et al.: Expandable metal stents for the palliation of malignant gastroduodenal obstruction. Cardiovasc Intervent Radiol 24 (5): 313-8, 2001 Sep-Oct. [PubMed: 11815836]
22. Baron TH, Rey JF, Spinelli P: Expandable metal stent placement for malignant colorectal obstruction. Endoscopy 34 (10): 823-30, 2002. [PubMed: 12244506]
23. De Conno F, Caraceni A, Zecca E, et al.: Continuous subcutaneous infusion of hyoscine butylbromide reduces secretions in patients with gastrointestinal obstruction. J Pain Symptom Manage 6 (8): 484-6, 1991. [PubMed: 1720156]
24. Ripamonti C, Mercadante S, Groff L, et al.: Role of octreotide, scopolamine butylbromide, and hydration in symptom control of patients with inoperable bowel obstruction and nasogastric tubes: a prospective randomized trial. J Pain Symptom Manage 19 (1): 23-34, 2000. [PubMed: 10687323]
25. Mystakidou K, Tsilika E, Kalaidopoulou O, et al.: Comparison of octreotide administration vs conservative treatment in the management of inoperable bowel obstruction in patients with far advanced cancer: a randomized, double- blind, controlled clinical trial. Anticancer Res 22 (2B): 1187-92, 2002 Mar-Apr. [PubMed: 12168923]
26. Fallon MT: The physiology of somatostatin and its synthetic analogue, octreotide. European Journal of Palliative Care 1 (1): 20-2, 1994.
27. Mercadante S: Assessment and management of mechanical bowel obstruction. In: Portenoy RK, Bruera E, eds.: Topics in Palliative Care. Volume 1. Oxford University Press, 1997, pp. 113-30.
28. Fainsinger RL: Integrating medical and surgical treatments in gastrointestinal, genitourinary, and biliary obstruction in patients with cancer. Hematol Oncol Clin North Am 10 (1): 173-88, 1996. [PubMed: 8821566]
29. Ripamonti C, Panzeri C, Groff L, et al.: The role of somatostatin and octreotide in bowel obstruction: pre-clinical and clinical results. Tumori 87 (1): 1-9, 2001 Jan-Feb. [PubMed: 11669548]
30. Davis M, Hui D, Davies A, et al.: Medical management of malignant bowel obstruction in patients with advanced cancer: 2021 MASCC guideline update. Support Care Cancer 29 (12): 8089-8096, 2021. [PubMed: 34390398]

Causes of Diarrhea

In patients being treated for cancer, diarrhea is most commonly induced by therapy.[14] Conventional methods of diarrhea-causing treatment include the following:

• Surgery.
• Chemotherapy.
• Immunotherapy.
• Radiation therapy.
• Bone marrow transplantation.

Other causes of acute diarrhea include the following:[15]

• Antibiotic therapy.
• Tube feeding.
• Stress and anxiety associated with cancer diagnosis and treatment.
• Infection.

Typical infections are of viral, bacterial, protozoan, parasitic, or fungal etiology. They may also be caused by pseudomembranous colitis, which often does not respond to treatment.[7] 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 3). 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.

Surgery, a primary treatment modality for many cancers, can affect the body by mechanical, functional, and physiological alterations. Postsurgical complications of gastrointestinal surgery that affect normal bowel function may contribute to diarrhea.[16]

Certain chemotherapeutic agents can alter normal absorption and secretion functions of the small bowel, resulting in treatment-related diarrhea (see Table 3 and Table 5). Patients who are 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 include the following:

• Total dose of radiation.
• Fractionation of radiation.
• Volume of bowel irradiated.
• Concomitant chemotherapy.

Acute intestinal side effects occur at approximately 10 Gy and may last up to 8 to 12 weeks posttherapy. Chronic radiation enteritis may occur months to years after therapy ends. This condition 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. It commonly affects the intestinal tract, skin, and liver. Symptoms of gastrointestinal GVHD include nausea and vomiting, severe abdominal pain and cramping, and watery diarrhea.[17] The volume of accompanying GVHD-associated diarrhea may reach up to several liters per day and is an indicator of the degree and extent of mucosal damage.[17] Acute GVHD is usually manifested within 100 days posttransplant, although it can occur as early as 7 to 10 days posttransplant. It may resolve or develop into a chronic form requiring long-term treatment and dietary management.

Table

Table 3. Possible Contributors to Diarrhea in Patients With Cancer.

Some chemotherapeutic agents result in grade 3 or 4 treatment-related diarrhea. Table 4 and Table 5 list the toxicity of intravenous and oral agents used to treat cancer, respectively.

Table

Table 4. Rate of Grade 3 or 4 Diarrhea Associated With Intravenous Chemotherapy^a.

Table

·Table 5. Rate of Grade 3 or 4 Diarrhea Associated With Oral Chemotherapy^a.

Assessment of Diarrhea

Rapid yet thorough assessment of diarrhea is imperative because of its potentially life-threatening nature. Few standardized assessment tools are available. As a result, standardized assessment is rare in the clinical setting.[7] 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, and a thorough description of the diarrhea. Stringent monitoring conducted at least weekly is indicated during therapy using chemotherapeutic agents known to cause diarrhea.[12] The NCI’s Common Terminology Criteria for Adverse Events (see Table 2) evaluate diarrhea by the following:[11]

• Number of stools per day.
• Incontinence.
• Increase in ostomy output compared with baseline.
• Interference with activities of daily living.
• Hospitalization.

The patient 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.[42] A visual tool to assist patients and families in characterizing the consistency of the stool has been developed.[43] Six diagrams illustrate fecal material consistency ranging from well-formed, formed, and semiformed to loose, very loose, and liquid.

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

• Dizziness.
• Orthostatic symptoms.
• Lethargy.
• Cramping.
• Abdominal pain.
• Nausea.
• Vomiting.
• Fever.
• Rectal bleeding.

These symptoms are classified as complicated or uncomplicated, with therapy based on these classifications.[44]

Uncomplicated diarrhea includes grade 1 or 2 diarrhea with no other signs or symptoms. Management is conservative.

Complicated diarrhea includes 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 1 in Nausea and Vomiting).
• Decreased performance status.
• Fever.
• Sepsis.
• Neutropenia.
• Frank bleeding.
• Dehydration.

Grade 3 or 4 diarrhea is also classified as complicated. Thorough evaluation and close monitoring is warranted.[44]

The time course of diarrhea and concomitant symptom development are key to determining the underlying etiology.[42] Medication and dietary intake, as well as a history of recent travel, may provide additional clues. 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 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.[18]

Laboratory tests may include the following:[18]

• Stool cultures for bacterial, fungal, and viral pathogens.
• A complete chemistry panel and hematologic profile. This will provide information regarding the effect of diarrhea on kidney function and electrolytes and identify changes in white blood cell count in response to infection.
• Urinalysis with specific gravity to 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 analyzed 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.[44]

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

1. Stein A, Voigt W, Jordan K: Chemotherapy-induced diarrhea: pathophysiology, frequency and guideline-based management. Ther Adv Med Oncol 2 (1): 51-63, 2010. [PMC free article: PMC3126005] [PubMed: 21789126]
2. Ascierto PA, Del Vecchio M, Robert C, et al.: Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol 18 (5): 611-622, 2017. [PubMed: 28359784]
3. Wang DY, Ye F, Zhao S, et al.: Incidence of immune checkpoint inhibitor-related colitis in solid tumor patients: A systematic review and meta-analysis. Oncoimmunology 6 (10): e1344805, 2017. [PMC free article: PMC5665065] [PubMed: 29123955]
4. Hellmann MD, Paz-Ares L, Bernabe Caro R, et al.: Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer. N Engl J Med 381 (21): 2020-2031, 2019. [PubMed: 31562796]
5. Larkin J, Chiarion-Sileni V, Gonzalez R, et al.: Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med 373 (1): 23-34, 2015. [PMC free article: PMC5698905] [PubMed: 26027431]
6. Motzer RJ, Tannir NM, McDermott DF, et al.: Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med 378 (14): 1277-1290, 2018. [PMC free article: PMC5972549] [PubMed: 29562145]
7. Rutledge DN, Engelking C: Cancer-related diarrhea: selected findings of a national survey of oncology nurse experiences. Oncol Nurs Forum 25 (5): 861-73, 1998. [PubMed: 9644702]
8. Cleeland CS, Mendoza TR, Wang XS, et al.: Assessing symptom distress in cancer patients: the M.D. Anderson Symptom Inventory. Cancer 89 (7): 1634-46, 2000. [PubMed: 11013380]
9. Wolfe J, Grier HE, Klar N, et al.: Symptoms and suffering at the end of life in children with cancer. N Engl J Med 342 (5): 326-33, 2000. [PubMed: 10655532]
10. Arbuckle RB, Huber SL, Zacker C: The consequences of diarrhea occurring during chemotherapy for colorectal cancer: a retrospective study. Oncologist 5 (3): 250-9, 2000. [PubMed: 10884503]
11. National Cancer Institute: Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. Bethesda, Md: U.S. Department of Health and Human Services, National Institutes of Health, 2017. Available online. Last accessed Feb. 14, 2024.
12. Rothenberg ML, Meropol NJ, Poplin EA, et al.: Mortality associated with irinotecan plus bolus fluorouracil/leucovorin: summary findings of an independent panel. J Clin Oncol 19 (18): 3801-7, 2001. [PubMed: 11559717]
13. Arnold RJ, Gabrail N, Raut M, et al.: Clinical implications of chemotherapy-induced diarrhea in patients with cancer. J Support Oncol 3 (3): 227-32, 2005 May-Jun. [PubMed: 15915825]
14. Cartoni C, Dragoni F, Micozzi A, et al.: Neutropenic enterocolitis in patients with acute leukemia: prognostic significance of bowel wall thickening detected by ultrasonography. J Clin Oncol 19 (3): 756-61, 2001. [PubMed: 11157028]
15. Tuchmann L, Engelking C: Cancer-related diarrhea. In: Gates RA, Fink RM, eds.: Oncology Nursing Secrets. 2nd ed. Hanley and Belfus, 2001, pp 310-22.
16. Yde J, Larsen HM, Laurberg S, et al.: Chronic diarrhoea following surgery for colon cancer-frequency, causes and treatment options. Int J Colorectal Dis 33 (6): 683-694, 2018. [PubMed: 29589108]
17. Naymagon S, Naymagon L, Wong SY, et al.: Acute graft-versus-host disease of the gut: considerations for the gastroenterologist. Nat Rev Gastroenterol Hepatol 14 (12): 711-726, 2017. [PMC free article: PMC6240460] [PubMed: 28951581]
18. Sykes NP: Constipation and diarrhoea. In: Doyle D, Hanks GW, MacDonald N, eds.: Oxford Textbook of Palliative Medicine. Oxford University Press, 1998, pp 513-26.
19. Mercadante S: Diarrhea in terminally ill patients: pathophysiology and treatment. J Pain Symptom Manage 10 (4): 298-309, 1995. [PubMed: 7602180]
20. Yahanda AM: Hepatobiliary cancers. In: Berger DH, Feig BW, Fuhrman GM, eds.: The M.D. Anderson Surgical Oncology Handbook. Little, Brown, 1995, pp 194-224.
21. Sonis S, Elting L, Keefe D, et al.: Unanticipated frequency and consequences of regimen-related diarrhea in patients being treated with radiation or chemoradiation regimens for cancers of the head and neck or lung. Support Care Cancer 23 (2): 433-9, 2015. [PubMed: 25123194]
22. Charuhas PM: Medical nutrition therapy in bone marrow transplantation. In: McCallum PD, Polisena CG, eds.: The Clinical Guide to Oncology Nutrition. The American Dietetic Association, 2000, pp 90-8.
23. DuPont HL: Guidelines on acute infectious diarrhea in adults. The Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol 92 (11): 1962-75, 1997. [PubMed: 9362174]
24. Lexicomp Online. Hudson, Ohio: Lexi-Comp, Inc., 2021. Available online with subscription. Last accessed July 17, 2024.
25. Iacovelli R, Pietrantonio F, Palazzo A, et al.: Incidence and relative risk of grade 3 and 4 diarrhoea in patients treated with capecitabine or 5-fluorouracil: a meta-analysis of published trials. Br J Clin Pharmacol 78 (6): 1228-37, 2014. [PMC free article: PMC4256612] [PubMed: 24962653]
26. NDA 20-954 Busulfex (busulfan) Injection. Minnetonka, Minn.: Orphan Medical, Inc., 1999. Available online. Last accessed Aug. 24, 2023.
27. Murthy RK, Loi S, Okines A, et al.: Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med 382 (7): 597-609, 2020. [PubMed: 31825569]
28. Curigliano G, Mueller V, Borges V, et al.: Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis. Ann Oncol 33 (3): 321-329, 2022. [PubMed: 34954044]
29. Leboulleux S, Bastholt L, Krause T, et al.: Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial. Lancet Oncol 13 (9): 897-905, 2012. [PubMed: 22898678]
30. Wells SA, Robinson BG, Gagel RF, et al.: Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol 30 (2): 134-41, 2012. [PMC free article: PMC3675689] [PubMed: 22025146]
31. Fowler NH, Samaniego F, Jurczak W, et al.: Umbralisib, a Dual PI3Kδ/CK1ε Inhibitor in Patients With Relapsed or Refractory Indolent Lymphoma. J Clin Oncol 39 (15): 1609-1618, 2021. [PMC free article: PMC8148421] [PubMed: 33683917]
32. Kim YH, Bagot M, Pinter-Brown L, et al.: Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Lancet Oncol 19 (9): 1192-1204, 2018. [PubMed: 30100375]
33. Schmitt T, Mayer-Steinacker R, Mayer F, et al.: Vorinostat in refractory soft tissue sarcomas - Results of a multi-centre phase II trial of the German Soft Tissue Sarcoma and Bone Tumour Working Group (AIO). Eur J Cancer 64: 74-82, 2016. [PubMed: 27367154]
34. Hong DS, Fakih MG, Strickler JH, et al.: KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors. N Engl J Med 383 (13): 1207-1217, 2020. [PMC free article: PMC7571518] [PubMed: 32955176]
35. Skoulidis F, Li BT, Dy GK, et al.: Sotorasib for Lung Cancers with KRAS p.G12C Mutation. N Engl J Med 384 (25): 2371-2381, 2021. [PMC free article: PMC9116274] [PubMed: 34096690]
36. Gounder MM, Razak AA, Somaiah N, et al.: Selinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial. J Clin Oncol 40 (22): 2479-2490, 2022. [PMC free article: PMC9467680] [PubMed: 35394800]
37. Kalakonda N, Maerevoet M, Cavallo F, et al.: Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial. Lancet Haematol 7 (7): e511-e522, 2020. [PubMed: 32589977]
38. Chari A, Vogl DT, Gavriatopoulou M, et al.: Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma. N Engl J Med 381 (8): 727-738, 2019. [PubMed: 31433920]
39. Escudier B, Eisen T, Stadler WM, et al.: Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356 (2): 125-34, 2007. [PubMed: 17215530]
40. Eisen T, Frangou E, Oza B, et al.: Adjuvant Sorafenib for Renal Cell Carcinoma at Intermediate or High Risk of Relapse: Results From the SORCE Randomized Phase III Intergroup Trial. J Clin Oncol 38 (34): 4064-4075, 2020. [PMC free article: PMC7768344] [PubMed: 33052759]
41. Llovet JM, Ricci S, Mazzaferro V, et al.: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359 (4): 378-90, 2008. [PubMed: 18650514]
42. Kornblau S, Benson AB, Catalano R, et al.: Management of cancer treatment-related diarrhea. Issues and therapeutic strategies. J Pain Symptom Manage 19 (2): 118-29, 2000. [PubMed: 10699539]
43. Mertz HR, Beck CK, Dixon W, et al.: Validation of a new measure of diarrhea. Dig Dis Sci 40 (9): 1873-82, 1995. [PubMed: 7555436]
44. Benson AB, Ajani JA, Catalano RB, et al.: Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol 22 (14): 2918-26, 2004. [PubMed: 15254061]
45. Polisena CG: Nutrition concerns with the radiation therapy patient. In: McCallum PD, Polisena CG, eds.: The Clinical Guide to Oncology Nutrition. The American Dietetic Association, 2000, pp 70-8.
46. McCallum PD, Polisena CG, eds.: The Clinical Guide to Oncology Nutrition. The American Dietetic Association, 2000.
47. Hogan CM: The nurse's role in diarrhea management. Oncol Nurs Forum 25 (5): 879-86, 1998. [PubMed: 9644704]
48. Kozelsky TF, Meyers GE, Sloan JA, et al.: Phase III double-blind study of glutamine versus placebo for the prevention of acute diarrhea in patients receiving pelvic radiation therapy. J Clin Oncol 21 (9): 1669-74, 2003. [PubMed: 12721240]
49. Savy GK: Glutamine supplementation. Heal the gut, help the patient. J Infus Nurs 25 (1): 65-9, 2002 Jan-Feb. [PubMed: 11840007]
50. Ziegler TR, Bye RL, Persinger RL, et al.: Effects of glutamine supplementation on circulating lymphocytes after bone marrow transplantation: a pilot study. Am J Med Sci 315 (1): 4-10, 1998. [PubMed: 9427568]
51. Cascinu S, Bichisao E, Amadori D, et al.: High-dose loperamide in the treatment of 5-fluorouracil-induced diarrhea in colorectal cancer patients. Support Care Cancer 8 (1): 65-7, 2000. [PubMed: 10650901]
52. Kehrer DF, Sparreboom A, Verweij J, et al.: Modulation of irinotecan-induced diarrhea by cotreatment with neomycin in cancer patients. Clin Cancer Res 7 (5): 1136-41, 2001. [PubMed: 11350876]
53. Takeda Y, Kobayashi K, Akiyama Y, et al.: Prevention of irinotecan (CPT-11)-induced diarrhea by oral alkalization combined with control of defecation in cancer patients. Int J Cancer 92 (2): 269-75, 2001. [PubMed: 11291056]
54. de Vrese M, Schrezenmeir J: Probiotics, prebiotics, and synbiotics. Adv Biochem Eng Biotechnol 111: 1-66, 2008. [PubMed: 18461293]
55. Isolauri E: Probiotics in human disease. Am J Clin Nutr 73 (6): 1142S-1146S, 2001. [PubMed: 11393192]
56. Johnston BC, Supina AL, Ospina M, et al.: Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev (2): CD004827, 2007. [PubMed: 17443557]
57. Pillai A, Nelson R: Probiotics for treatment of Clostridium difficile-associated colitis in adults. Cochrane Database Syst Rev (1): CD004611, 2008. [PubMed: 18254055]
58. Huertas-Ceballos A, Logan S, Bennett C, et al.: Dietary interventions for recurrent abdominal pain (RAP) and irritable bowel syndrome (IBS) in childhood. Cochrane Database Syst Rev (1): CD003019, 2008. [PubMed: 18254014]
59. Alfaleh K, Bassler D: Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev (1): CD005496, 2008. [PubMed: 18254081]
60. Karimi O, Peña AS: Indications and challenges of probiotics, prebiotics, and synbiotics in the management of arthralgias and spondyloarthropathies in inflammatory bowel disease. J Clin Gastroenterol 42 (Suppl 3 Pt 1): S136-41, 2008. [PubMed: 18806706]
61. Butterworth AD, Thomas AG, Akobeng AK: Probiotics for induction of remission in Crohn's disease. Cochrane Database Syst Rev (3): CD006634, 2008. [PMC free article: PMC6544811] [PubMed: 18646162]
62. Eghbali A, Ghaffari K, Khalilpour A, et al.: The effects of LactoCare synbiotic administration on chemotherapy-induced nausea, vomiting, diarrhea, and constipation in children with ALL: A double-blind randomized clinical trial. Pediatr Blood Cancer 70 (6): e30328, 2023. [PubMed: 36975174]
63. Delia P, Sansotta G, Donato V, et al.: Use of probiotics for prevention of radiation-induced diarrhea. World J Gastroenterol 13 (6): 912-5, 2007. [PMC free article: PMC4065928] [PubMed: 17352022]
64. Cello JP, Grendell JH, Basuk P, et al.: Effect of octreotide on refractory AIDS-associated diarrhea. A prospective, multicenter clinical trial. Ann Intern Med 115 (9): 705-10, 1991. [PubMed: 1929038]
65. Cascinu S, Fedeli A, Fedeli SL, et al.: Octreotide versus loperamide in the treatment of fluorouracil-induced diarrhea: a randomized trial. J Clin Oncol 11 (1): 148-51, 1993. [PubMed: 8418225]
66. Cascinu S, Fedeli A, Fedeli SL, et al.: Control of chemotherapy-induced diarrhea with octreotide. A randomized trial with placebo in patients receiving cisplatin. Oncology 51 (1): 70-3, 1994 Jan-Feb. [PubMed: 8265106]
67. Gebbia V, Carreca I, Testa A, et al.: Subcutaneous octreotide versus oral loperamide in the treatment of diarrhea following chemotherapy. Anticancer Drugs 4 (4): 443-5, 1993. [PubMed: 8400346]
68. Petrelli NJ, Rodriguez-Bigas M, Rustum Y, et al.: Bowel rest, intravenous hydration, and continuous high-dose infusion of octreotide acetate for the treatment of chemotherapy-induced diarrhea in patients with colorectal carcinoma. Cancer 72 (5): 1543-6, 1993. [PubMed: 8348489]
69. Wadler S, Haynes H, Wiernik PH: Phase I trial of the somatostatin analog octreotide acetate in the treatment of fluoropyrimidine-induced diarrhea. J Clin Oncol 13 (1): 222-6, 1995. [PubMed: 7799023]
70. Cascinu S, Fedeli A, Fedeli SL, et al.: Control of chemotherapy-induced diarrhoea with octreotide in patients receiving 5-fluorouracil. Eur J Cancer 28 (2-3): 482-3, 1992. [PubMed: 1591068]
71. Zidan J, Haim N, Beny A, et al.: Octreotide in the treatment of severe chemotherapy-induced diarrhea. Ann Oncol 12 (2): 227-9, 2001. [PubMed: 11300329]
72. Ippoliti C, Champlin R, Bugazia N, et al.: Use of octreotide in the symptomatic management of diarrhea induced by graft-versus-host disease in patients with hematologic malignancies. J Clin Oncol 15 (11): 3350-4, 1997. [PubMed: 9363865]
73. Morton AJ, Durrant ST: Efficacy of octreotide in controlling refractory diarrhea following bone marrow transplantation. Clin Transplant 9 (3 Pt 1): 205-8, 1995. [PubMed: 7549062]
74. Martenson JA, Halyard MY, Sloan JA, et al.: Phase III, double-blind study of depot octreotide versus placebo in the prevention of acute diarrhea in patients receiving pelvic radiation therapy: results of North Central Cancer Treatment Group N00CA. J Clin Oncol 26 (32): 5248-53, 2008. [PMC free article: PMC2652088] [PubMed: 18768432]
75. Tandon P, Bourassa-Blanchette S, Bishay K, et al.: The Risk of Diarrhea and Colitis in Patients With Advanced Melanoma Undergoing Immune Checkpoint Inhibitor Therapy: A Systematic Review and Meta-Analysis. J Immunother 41 (3): 101-108, 2018. [PubMed: 29401166]
76. Rocha M, Correia de Sousa J, Salgado M, et al.: Management of Gastrointestinal Toxicity from Immune Checkpoint Inhibitor. GE Port J Gastroenterol 26 (4): 268-274, 2019. [PMC free article: PMC6624661] [PubMed: 31328141]
77. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Management of Immunotherapy-Related Toxicities. Version 1.2023. Plymouth Meeting, Pa: National Comprehensive Cancer Network, 2023. Available with free registration. Last accessed May 6, 2023. [PubMed: 35390769]
78. ZYDELIG (idelalisib): highlights of prescribing information. Foster City, Calif: Gilead Sciences, Inc., 2022. Available online. Last accessed May 6, 2023.
79. COPIKTRA (duvelisib): highlights of prescribing information. Needham, Mass: Verastem Inc, 2018. Available online. Last accessed May 6, 2023.
80. Coutré SE, Barrientos JC, Brown JR, et al.: Management of adverse events associated with idelalisib treatment: expert panel opinion. Leuk Lymphoma 56 (10): 2779-86, 2015. [PMC free article: PMC4732460] [PubMed: 25726955]

Causes of Radiation Enteritis

Almost all patients undergoing radiation to the abdomen, pelvis, or rectum will show signs of acute enteritis. Injuries are clinically evident during or within 3 months after irradiation, with the greatest prevalence during the fourth and fifth weeks.[1] Chronic radiation enteritis may present months to years after the completion of therapy, or it may begin as acute enteritis and persist after treatment ends. Only 10% to 20% of people treated with radiation to the abdomen develop chronic problems.[2]

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 with an exposure of approximately 10 Gy. Because curative radiation doses for many abdominal or pelvic tumors range between 25 and 76 Gy, enteritis is likely to occur.[2]

Factors that influence the occurrence and severity of radiation enteritis include the following:[2]

• Dose and fractionation of radiation.
• Modality of radiation.
• Tumor size and extent.
• Volume of normal bowel treated.
• Concomitant chemotherapy.
• Individual patient variables (e.g., previous abdominal or pelvic surgery, hypertension, diabetes mellitus, smoking, inadequate nutrition).

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

Chronic Radiation Enteritis

References

1. Harb AH, Abou Fadel C, Sharara AI: Radiation enteritis. Curr Gastroenterol Rep 16 (5): 383, 2014. [PubMed: 24604730]
2. Loge L, Florescu C, Alves A, et al.: Radiation enteritis: Diagnostic and therapeutic issues. J Visc Surg 157 (6): 475-485, 2020. [PubMed: 32883650]
3. Gusev IA, Guskova AK, Mettler FA: Medical Management of Radiation Accidents. 2nd ed. CRC Press/Taylor & Francis Group, 2001. Also available online. Last accessed May 6, 2023.
4. Sonis S, Elting L, Keefe D, et al.: Unanticipated frequency and consequences of regimen-related diarrhea in patients being treated with radiation or chemoradiation regimens for cancers of the head and neck or lung. Support Care Cancer 23 (2): 433-9, 2015. [PubMed: 25123194]
5. Hille A, Christiansen H, Pradier O, et al.: Effect of pentoxifylline and tocopherol on radiation proctitis/enteritis. Strahlenther Onkol 181 (9): 606-14, 2005. [PubMed: 16170489]
6. Stryker JA, Bartholomew M: Failure of lactose-restricted diets to prevent radiation-induced diarrhea in patients undergoing whole pelvis irradiation. Int J Radiat Oncol Biol Phys 12 (5): 789-92, 1986. [PubMed: 3086261]
7. Yasko JM: Care of the Client Receiving External Radiation Therapy. Reston Publishing Company, Inc., 1982.
8. Mendelson RM, Nolan DJ: The radiological features of chronic radiation enteritis. Clin Radiol 36 (2): 141-8, 1985. [PubMed: 4064491]
9. Lillemoe KD, Brigham RA, Harmon JW, et al.: Surgical management of small-bowel radiation enteritis. Arch Surg 118 (8): 905-7, 1983. [PubMed: 6870521]
10. Wobbes T, Verschueren RC, Lubbers EJ, et al.: Surgical aspects of radiation enteritis of the small bowel. Dis Colon Rectum 27 (2): 89-92, 1984. [PubMed: 6697836]
11. Wellwood JM, Jackson BT: The intestinal complications of radiotherapy. Br J Surg 60 (10): 814-8, 1973. [PubMed: 4748388]
12. Minsky BD, Cohen AM: Minimizing the toxicity of pelvic radiation therapy in rectal cancer. Oncology (Huntingt) 2 (8): 21-5, 28-9, 1988. [PubMed: 3275055]

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:

• be discussed at a meeting,
• be cited with text, or
• replace or update an existing article that is already cited.

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:

• Alison Palumbo, PharmD, MPH, BCOP (Oregon Health and Science University Hospital)
• Maria Petzel, RD, CSO, LD, CNSC, FAND (University of TX MD Anderson Cancer Center)
• Megan Reimann, PharmD, BCOP (Total CME)

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.

Permission to Use This Summary

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

The preferred citation for this PDQ summary is:

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

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

The information in these summaries should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

Contact Us

More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website’s Email Us.