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Gastrointestinal Complications (PDQ®)

Health Professional Version

Diarrhea

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

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

Table 1. National Cancer Institute's Common Terminology Criteria for Adverse Events: Diarrheaa,b
GradeDescription
ADL = activities of daily living.
aAdapted from National Cancer Institute.[8]
bDefinition: A disorder characterized by frequent and watery bowel movements.
cSelf-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.
1Increase of <4 stools/day over baseline; mild increase in ostomy output compared with baseline
2Increase of 4–6 stools/day over baseline; moderate increase in ostomy output compared with baseline
3Increase of ≥7 stools/day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared with baseline; limiting self-care ADLc
4Life-threatening consequences; urgent intervention indicated
5Death

Etiology of Diarrhea

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

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

Other causes of acute diarrhea include the following:[12]

  • Antibiotic therapy.
  • 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, a cause of diarrhea that often does not respond to treatment.[3] Clostridium difficile is a common cause of pseudomembranous colitis.

Other causes of diarrhea in patients with cancer include the underlying cancer, responses to diet, or concomitant diseases (see Table 2). Common causes of diarrhea in patients receiving palliative care are difficulty adjusting the laxative regimen and impaction leading to leakage of stool around the fecal obstruction.

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

Surgery, a primary treatment modality for many cancers, can affect the body by mechanical, functional, and physiological alterations. Postsurgical complications of gastrointestinal surgery affecting normal bowel function that may contribute to diarrhea include the following:[14,15]

  • Increased transit time.
  • Gastroparesis.
  • Fat malabsorption.
  • Lactose intolerance.
  • Fluid and electrolyte imbalance.
  • Dumping syndrome.

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

Radiation therapy to abdominal, pelvic, lumbar, or para-aortic fields can result in changes to normal bowel function. Factors contributing to the occurrence and severity of intestinal complications depend on the following:

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

Common side effects of intestinal enteritis include the following:

  • Diarrhea.
  • Malabsorption.
  • Gas.
  • Bloating.
  • Cramping.

Acute intestinal side effects occur at approximately 10 Gy and may last up to 8 to 12 weeks posttherapy. Chronic radiation enteritis may present months to years after completion of therapy and necessitates dietary modification and pharmacological management and, in some instances, surgical intervention. (Refer to the Radiation Enteritis section of this summary for more information.)

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

Table 2. Possible Contributions to Diarrhea in Cancer
Cancer-related [5,18]Carcinoid syndrome
Colon cancer
Lymphoma
Medullary carcinoma of the thyroid
Pancreatic cancer, particularly islet cell tumors (Zollinger-Ellison syndrome)
Pheochromocytoma
Surgery- or procedure-related [14]Celiac plexus block
Cholecystectomy, esophagogastrectomy
Gastrectomy, pancreaticoduodenectomy (Whipple procedure)
Intestinal resection (malabsorption due to short bowel syndrome)
Vagotomy
Chemotherapy-related [19-21]Capecitabine, cisplatin, cytosine arabinoside, cyclophosphamide, daunorubicin, docetaxel, doxorubicin, 5-fluorouracil, interferon, irinotecan, leucovorin, methotrexate, oxaliplatin, paclitaxel, topotecan, lapatinib
Radiation therapy–related (Refer to the Radiation Enteritis section of this summary for more information.) [22,23]Irradiation to the abdomen, para-aortics, lumbar, and pelvis
Bone marrow transplantation–related [24]Conditioning chemotherapy, total-body irradiation, graft-versus-host disease after allogeneic bone marrow or peripheral blood stem cell transplants
Drug adverse effects [5,18]Antibiotics, magnesium-containing antacids, antihypertensives, colchicine, digoxin, iron, lactulose, laxatives, methyldopa, metoclopramide, misoprostol, potassium supplements, propranolol, theophylline
Concurrent disease [5,18]Diabetes, hyperthyroidism, inflammatory bowel disease (Crohn disease, diverticulitis, gastroenteritis, HIV/AIDS, ulcerative colitis), obstruction (tumor-related)
Infection [25]Clostridium difficile, Clostridium perfringens, Bacillus cereus, Giardia lamblia, Cryptosporidium, Salmonella, Shigella, Campylobacter, Rotavirus
Fecal impaction [5,18]Constipation leading to obstruction
Diet [5,18]Alcohol, milk, and dairy products (particularly in patients with lactose intolerance)
Caffeine-containing products (coffee, tea, chocolate); specific fruit juices (prune juice, unfiltered apple juice, sauerkraut juice)
High-fiber foods (raw fruits and vegetables, nuts, seeds, whole-grain products, dried legumes); high-fat foods (deep-fried foods, high fat–containing foods)
Lactulose intolerance or food allergies
Sorbitol-containing foods (candy and chewing gum); hot and spicy foods; gas-forming foods and beverages (cruciferous vegetables, dried legumes, melons, carbonated beverages)
Psychological factors [18]Stress

Assessment

Rapid, yet thorough, assessment of diarrhea is imperative because of the potentially life-threatening nature of diarrhea. Few standardized assessment tools are available, and studies suggest that, as a result, standardized assessment is rare in the clinical setting.[3] For a complete assessment, one author suggests obtaining background information from the patient that includes the type and extent of the patient’s cancer, anticancer treatment, comorbid factors, coexisting symptoms, patient and provider perceptions, as well as a thorough description of the diarrhea. Stringent monitoring conducted at least weekly is indicated during therapy using chemotherapeutic agents known to cause diarrhea.[9] The NCI’s Common Terminology Criteria for Adverse Events (Table 1) evaluate diarrhea by the following:[8]

  • Number of stools per day.
  • Incontinence.
  • Increase in ostomy output compared with baseline.

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.[26] One author has developed a visual tool to assist patients and families in characterizing the consistency of the stool.[27] Six diagrams illustrate fecal material consistency ranging from well-formed, formed, and semiformed to loose, very loose, and liquid.

Patients 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.[28]

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

Complicated symptoms include grade 1 or 2 diarrhea with any one of the following risk factors:

  • Moderate to severe cramping.
  • Grade 2 or higher nausea/vomiting (see Table 3).
  • 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.[28]

The time course of diarrhea and concomitant symptom development are key to determining underlying etiology.[26] Medication and dietary intake, as well as a history of recent travel, may provide additional clues regarding etiology. Weight loss and reduced urine output provide additional data regarding the severity of the effects of diarrhea.

Table 3. National Cancer Institute’s Common Terminology Criteria for Adverse Events: Nausea and Vomitinga
Adverse EventGradeDescription
TPN = total parenteral nutrition.
aAdapted from National Cancer Institute.[8]
bDefinition: A disorder characterized by a queasy sensation and/or the urge to vomit.
cDefinition: A disorder characterized by the reflexive act of ejecting the contents of the stomach through the mouth.
Nauseab1Loss of appetite without alteration in eating habits
2Oral intake decreased without significant weight loss, dehydration, or malnutrition
3Inadequate oral caloric or fluid intake; tube feeding, TPN, or hospitalization indicated
4Grade not available
5Grade not available
Vomitingc11–2 episodes (separated by 5 min) in 24 h
23–5 episodes (separated by 5 min) in 24 h
3≥6 episodes (separated by 5 min) in 24 h; tube feeding, TPN, or hospitalization indicated
4Life-threatening consequences; urgent intervention indicated
5Death

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

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

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

Management

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

Uncomplicated symptoms

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

While some case reports suggest the efficacy of glutamine in relieving diarrhea and other gastrointestinal symptoms associated with cancer therapy, one randomized controlled trial that used oral glutamine to prevent pelvic radiation-induced diarrhea was unable to demonstrate any benefit.[32][Level of evidence: I][33,34]

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

Opioids bind to receptors within the gastrointestinal tract and reduce diarrhea by reducing transit time. Loperamide is the most common opioid used, due to its availability and reduced effect on cognition, although codeine and other opioids can also be effective.[18] Common loperamide doses begin with 4 mg, followed by 2 mg after each unformed stool with a maximum of approximately 12 mg/day.[5,26] Regardless of the dose, however, loperamide may be less effective in patients with grade 3 or 4 diarrhea.[35][Level of evidence: I]

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

Other pharmacologic therapies for the relief of diarrhea may be specific to the underlying mechanism. Delayed diarrhea (>24 hours) occurs with irinotecan and can be severe in 25% of patients.[36] In a small study of seven patients, six patients obtained relief with oral neomycin, 1,000 mg 3 times daily. This relief occurred without reduction in the active metabolite of irinotecan, SN-38; thus, the poorly metabolized antibiotic did not alter efficacy of the chemotherapeutic agent.[37][Level of evidence: II] In another small study of 37 patients with non-small cell lung cancer receiving irinotecan, investigators alkalized the feces through oral administration of sodium bicarbonate, basic water, and ursodeoxycholic acid, while speeding transit time of the drug metabolites (thought to reduce damage to the intestinal lumen by reducing stasis of the drug) through the use of magnesium oxide. The incidence of delayed diarrhea was significantly reduced in this group when compared with 32 patients receiving the same chemotherapeutic regimen without oral alkalization and controlled defecation.[38][Level of evidence: III]

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

Probiotics

Probiotics are nutritional supplements that contain a defined amount of viable microorganisms and, upon administration, confer a benefit to the patient.[39] The use of probiotic functional foods (beneficial live microorganisms) to modify gut microflora has been suggested in clinical conditions associated with diarrhea, gut-barrier dysfunction, and inflammatory response.[40] There are a vast number of different strains of probiotics; however, much of the clinical research has investigated the species belonging to the family of Lactobacillus and Bifidobacterium. Probiotics have been promoted for the following:[41-46]

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

The results of one study among adults with cancer have been published. In a double-blind, randomized, controlled trial, 450 adults with cancer who were receiving radiation to the pelvic region were randomly assigned to receive the blend probiotic product VSL #3 or placebo during radiation therapy. The authors reported a decrease in the incidence and severity of diarrhea. No adverse events were reported.[47]

Clinical trials for the following patients are under way:

  • Patients with familial adenomatous polyposis (NCT00319007).
  • Patients undergoing donor stem cell transplantation for hematologic cancer or myelodysplastic syndrome (NCT00946283). This trial is now closed to accrual.

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.[28] Particularly when patients are receiving chemotherapy, additional evaluation includes stool workup (including blood, fecal leukocytes, C. difficile, Salmonella, E. coli, Campylobacter, and infectious colitis), complete blood count, and electrolyte profile.[28] This workup and treatment is also considered for patients who progress to grade 3 or 4 diarrhea while taking loperamide. The same panel suggests that severe radiation therapy–induced diarrhea may not require hospitalization (an alternative outpatient unit or intensive home care nursing may be able to provide the same level of care and monitoring) but the patient's constellation of symptoms are considered to determine the appropriate workup and whether IV fluids or octreotide is indicated.

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

Current Clinical Trials

Check NCI’s list of cancer clinical trials for U.S. supportive and palliative care trials about diarrhea that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.

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

References

  1. Leichman CG, Fleming TR, Muggia FM, et al.: Phase II study of fluorouracil and its modulation in advanced colorectal cancer: a Southwest Oncology Group study. J Clin Oncol 13 (6): 1303-11, 1995. [PUBMED Abstract]
  2. Rothenberg ML, Eckardt JR, Kuhn JG, et al.: Phase II trial of irinotecan in patients with progressive or rapidly recurrent colorectal cancer. J Clin Oncol 14 (4): 1128-35, 1996. [PUBMED Abstract]
  3. Rutledge DN, Engelking C: Cancer-related diarrhea: selected findings of a national survey of oncology nurse experiences. Oncol Nurs Forum 25 (5): 861-73, 1998. [PUBMED Abstract]
  4. Cleeland CS, Mendoza TR, Wang XS, et al.: Assessing symptom distress in cancer patients: the M.D. Anderson Symptom Inventory. Cancer 89 (7): 1634-46, 2000. [PUBMED Abstract]
  5. Sykes NP: Constipation and diarrhoea. In: Doyle D, Hanks GW, MacDonald N, eds.: Oxford Textbook of Palliative Medicine. 2nd ed. New York, NY: Oxford University Press, 1998, pp 513-26.
  6. Wolfe J, Grier HE, Klar N, et al.: Symptoms and suffering at the end of life in children with cancer. N Engl J Med 342 (5): 326-33, 2000. [PUBMED Abstract]
  7. Arbuckle RB, Huber SL, Zacker C: The consequences of diarrhea occurring during chemotherapy for colorectal cancer: a retrospective study. Oncologist 5 (3): 250-9, 2000. [PUBMED Abstract]
  8. National Cancer Institute: Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0. Bethesda, Md: U.S. Department of Health and Human Services, National Institutes of Health, 2010. Available online. Last accessed August 28, 2014.
  9. Rothenberg ML, Meropol NJ, Poplin EA, et al.: Mortality associated with irinotecan plus bolus fluorouracil/leucovorin: summary findings of an independent panel. J Clin Oncol 19 (18): 3801-7, 2001. [PUBMED Abstract]
  10. Arnold RJ, Gabrail N, Raut M, et al.: Clinical implications of chemotherapy-induced diarrhea in patients with cancer. J Support Oncol 3 (3): 227-32, 2005 May-Jun. [PUBMED Abstract]
  11. Cartoni C, Dragoni F, Micozzi A, et al.: Neutropenic enterocolitis in patients with acute leukemia: prognostic significance of bowel wall thickening detected by ultrasonography. J Clin Oncol 19 (3): 756-61, 2001. [PUBMED Abstract]
  12. Tuchmann L, Engelking C: Cancer-related diarrhea. In: Gates RA, Fink RM, eds.: Oncology Nursing Secrets. 2nd ed. Philadelphia, Pa: Hanley and Belfus, 2001, pp 310-22.
  13. Bruckstein AH: Acute diarrhea. Am Fam Physician 38 (4): 217-28, 1988. [PUBMED Abstract]
  14. Yahanda AM: Hepatobiliary cancers. In: Berger DH, Feig BW, Fuhrman GM, eds.: The M.D. Anderson Surgical Oncology Handbook. Boston, Mass: Little, Brown, 1995, pp 194-224.
  15. Grant JP, Chapman G, Russell MK: Malabsorption associated with surgical procedures and its treatment. Nutr Clin Pract 11 (2): 43-52, 1996. [PUBMED Abstract]
  16. McDonald GB, Shulman HM, Sullivan KM, et al.: Intestinal and hepatic complications of human bone marrow transplantation. Part I. Gastroenterology 90 (2): 460-77, 1986. [PUBMED Abstract]
  17. Herrmann VM, Petruska PJ: Nutrition support in bone marrow transplant recipients. Nutr Clin Pract 8 (1): 19-27, 1993. [PUBMED Abstract]
  18. Mercadante S: Diarrhea in terminally ill patients: pathophysiology and treatment. J Pain Symptom Manage 10 (4): 298-309, 1995. [PUBMED Abstract]
  19. Gupta E, Lestingi TM, Mick R, et al.: Metabolic fate of irinotecan in humans: correlation of glucuronidation with diarrhea. Cancer Res 54 (14): 3723-5, 1994. [PUBMED Abstract]
  20. Wadler S, Benson AB 3rd, Engelking C, et al.: Recommended guidelines for the treatment of chemotherapy-induced diarrhea. J Clin Oncol 16 (9): 3169-78, 1998. [PUBMED Abstract]
  21. Crown JP, Burris HA 3rd, Boyle F, et al.: Pooled analysis of diarrhea events in patients with cancer treated with lapatinib. Breast Cancer Res Treat 112 (2): 317-25, 2008. [PUBMED Abstract]
  22. Makrauer FL, Oates E, Becker J, et al.: Does local irradiation affect gastric emptying in humans? Am J Med Sci 317 (1): 33-7, 1999. [PUBMED Abstract]
  23. Donaldson SS: Nutritional consequences of radiotherapy. Cancer Res 37 (7 Pt 2): 2407-13, 1977. [PUBMED Abstract]
  24. Charuhas PM: Medical nutrition therapy in bone marrow transplantation. In: McCallum PD, Polisena CG, eds.: The Clinical Guide to Oncology Nutrition. Chicago, Ill: The American Dietetic Association, 2000, pp 90-8.
  25. DuPont HL: Guidelines on acute infectious diarrhea in adults. The Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol 92 (11): 1962-75, 1997. [PUBMED Abstract]
  26. Kornblau S, Benson AB, Catalano R, et al.: Management of cancer treatment-related diarrhea. Issues and therapeutic strategies. J Pain Symptom Manage 19 (2): 118-29, 2000. [PUBMED Abstract]
  27. Mertz HR, Beck CK, Dixon W, et al.: Validation of a new measure of diarrhea. Dig Dis Sci 40 (9): 1873-82, 1995. [PUBMED Abstract]
  28. Benson AB 3rd, Ajani JA, Catalano RB, et al.: Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol 22 (14): 2918-26, 2004. [PUBMED Abstract]
  29. Polisena CG: Nutrition concerns with the radiation therapy patient. In: McCallum PD, Polisena CG, eds.: The Clinical Guide to Oncology Nutrition. Chicago, Ill: The American Dietetic Association, 2000, pp 70-8.
  30. McCallum PD, Polisena CG, eds.: The Clinical Guide to Oncology Nutrition. Chicago, Ill: The American Dietetic Association, 2000.
  31. Hogan CM: The nurse's role in diarrhea management. Oncol Nurs Forum 25 (5): 879-86, 1998. [PUBMED Abstract]
  32. Kozelsky TF, Meyers GE, Sloan JA, et al.: Phase III double-blind study of glutamine versus placebo for the prevention of acute diarrhea in patients receiving pelvic radiation therapy. J Clin Oncol 21 (9): 1669-74, 2003. [PUBMED Abstract]
  33. Savy GK: Glutamine supplementation. Heal the gut, help the patient. J Infus Nurs 25 (1): 65-9, 2002 Jan-Feb. [PUBMED Abstract]
  34. Ziegler TR, Bye RL, Persinger RL, et al.: Effects of glutamine supplementation on circulating lymphocytes after bone marrow transplantation: a pilot study. Am J Med Sci 315 (1): 4-10, 1998. [PUBMED Abstract]
  35. Cascinu S, Bichisao E, Amadori D, et al.: High-dose loperamide in the treatment of 5-fluorouracil-induced diarrhea in colorectal cancer patients. Support Care Cancer 8 (1): 65-7, 2000. [PUBMED Abstract]
  36. Creemers GJ, Lund B, Verweij J: Topoisomerase I inhibitors: topotecan and irenotecan. Cancer Treat Rev 20 (1): 73-96, 1994. [PUBMED Abstract]
  37. Kehrer DF, Sparreboom A, Verweij J, et al.: Modulation of irinotecan-induced diarrhea by cotreatment with neomycin in cancer patients. Clin Cancer Res 7 (5): 1136-41, 2001. [PUBMED Abstract]
  38. Takeda Y, Kobayashi K, Akiyama Y, et al.: Prevention of irinotecan (CPT-11)-induced diarrhea by oral alkalization combined with control of defecation in cancer patients. Int J Cancer 92 (2): 269-75, 2001. [PUBMED Abstract]
  39. de Vrese M, Schrezenmeir J: Probiotics, prebiotics, and synbiotics. Adv Biochem Eng Biotechnol 111: 1-66, 2008. [PUBMED Abstract]
  40. Isolauri E: Probiotics in human disease. Am J Clin Nutr 73 (6): 1142S-1146S, 2001. [PUBMED Abstract]
  41. Johnston BC, Supina AL, Ospina M, et al.: Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev (2): CD004827, 2007. [PUBMED Abstract]
  42. Pillai A, Nelson R: Probiotics for treatment of Clostridium difficile-associated colitis in adults. Cochrane Database Syst Rev (1): CD004611, 2008. [PUBMED Abstract]
  43. Huertas-Ceballos A, Logan S, Bennett C, et al.: Dietary interventions for recurrent abdominal pain (RAP) and irritable bowel syndrome (IBS) in childhood. Cochrane Database Syst Rev (1): CD003019, 2008. [PUBMED Abstract]
  44. Alfaleh K, Bassler D: Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev (1): CD005496, 2008. [PUBMED Abstract]
  45. Karimi O, Peña AS: Indications and challenges of probiotics, prebiotics, and synbiotics in the management of arthralgias and spondyloarthropathies in inflammatory bowel disease. J Clin Gastroenterol 42 (Suppl 3 Pt 1): S136-41, 2008. [PUBMED Abstract]
  46. Butterworth AD, Thomas AG, Akobeng AK: Probiotics for induction of remission in Crohn's disease. Cochrane Database Syst Rev (3): CD006634, 2008. [PUBMED Abstract]
  47. Delia P, Sansotta G, Donato V, et al.: Use of probiotics for prevention of radiation-induced diarrhea. World J Gastroenterol 13 (6): 912-5, 2007. [PUBMED Abstract]
  48. Cello JP, Grendell JH, Basuk P, et al.: Effect of octreotide on refractory AIDS-associated diarrhea. A prospective, multicenter clinical trial. Ann Intern Med 115 (9): 705-10, 1991. [PUBMED Abstract]
  49. Cascinu S, Fedeli A, Fedeli SL, et al.: Octreotide versus loperamide in the treatment of fluorouracil-induced diarrhea: a randomized trial. J Clin Oncol 11 (1): 148-51, 1993. [PUBMED Abstract]
  50. Cascinu S, Fedeli A, Fedeli SL, et al.: Control of chemotherapy-induced diarrhea with octreotide. A randomized trial with placebo in patients receiving cisplatin. Oncology 51 (1): 70-3, 1994 Jan-Feb. [PUBMED Abstract]
  51. Gebbia V, Carreca I, Testa A, et al.: Subcutaneous octreotide versus oral loperamide in the treatment of diarrhea following chemotherapy. Anticancer Drugs 4 (4): 443-5, 1993. [PUBMED Abstract]
  52. Petrelli NJ, Rodriguez-Bigas M, Rustum Y, et al.: Bowel rest, intravenous hydration, and continuous high-dose infusion of octreotide acetate for the treatment of chemotherapy-induced diarrhea in patients with colorectal carcinoma. Cancer 72 (5): 1543-6, 1993. [PUBMED Abstract]
  53. Wadler S, Haynes H, Wiernik PH: Phase I trial of the somatostatin analog octreotide acetate in the treatment of fluoropyrimidine-induced diarrhea. J Clin Oncol 13 (1): 222-6, 1995. [PUBMED Abstract]
  54. Cascinu S, Fedeli A, Fedeli SL, et al.: Control of chemotherapy-induced diarrhoea with octreotide in patients receiving 5-fluorouracil. Eur J Cancer 28 (2-3): 482-3, 1992. [PUBMED Abstract]
  55. Zidan J, Haim N, Beny A, et al.: Octreotide in the treatment of severe chemotherapy-induced diarrhea. Ann Oncol 12 (2): 227-9, 2001. [PUBMED Abstract]
  56. Ippoliti C, Champlin R, Bugazia N, et al.: Use of octreotide in the symptomatic management of diarrhea induced by graft-versus-host disease in patients with hematologic malignancies. J Clin Oncol 15 (11): 3350-4, 1997. [PUBMED Abstract]
  57. Morton AJ, Durrant ST: Efficacy of octreotide in controlling refractory diarrhea following bone marrow transplantation. Clin Transplant 9 (3 Pt 1): 205-8, 1995. [PUBMED Abstract]
  58. Martenson JA, Halyard MY, Sloan JA, et al.: Phase III, double-blind study of depot octreotide versus placebo in the prevention of acute diarrhea in patients receiving pelvic radiation therapy: results of North Central Cancer Treatment Group N00CA. J Clin Oncol 26 (32): 5248-53, 2008. [PUBMED Abstract]
  • Updated: August 28, 2014