Table 1. National Cancer Institute's Common Terminology Criteria for Adverse Events: Diarrheaa,b continued...
Another strategy for categorizing the causes of diarrhea is by putative underlying mechanisms. These include exudative (i.e., excess blood or mucous enters the gastrointestinal tract), malabsorptive, dysmotile, osmotic, and secretory (due to increased secretion of electrolytes and fluid—probably the mechanism underlying chemotherapy-induced diarrhea) factors or combinations of these factors.
Surgery, a primary treatment modality for many cancers, can affect the body by mechanical, functional, and physiological alterations. Postsurgical complications of gastrointestinal surgery affecting normal bowel function that may contribute to diarrhea include increased transit time, gastroparesis, fat malabsorption, lactose intolerance, fluid and electrolyte imbalance, and dumping syndrome.[14,15]
Certain chemotherapeutic agents can alter normal absorption and secretion functions of the small bowel, resulting in treatment-related diarrhea. Examples of chemotherapy agents with diarrhea-related potential are listed in Table 2. Patients receiving concomitant abdominal or pelvic radiation therapy or recovering from recent gastrointestinal surgery will often experience more severe diarrhea.
Radiation therapy to abdominal, pelvic, lumbar, or para-aortic fields can result in changes to normal bowel function. Factors contributing to the occurrence and severity of intestinal complications depend on total dose, fractionation, volume of bowel irradiated, and concomitant chemotherapy. Common side effects of intestinal enteritis include diarrhea, malabsorption, gas, bloating, and cramping. Acute intestinal side effects occur at approximately 10 Gy and may last up to 8 to 12 weeks posttherapy. Chronic radiation enteritis may present months to years after completion of therapy and necessitates dietary modification and pharmacological management and, in some instances, surgical intervention. (Refer to the Radiation Enteritis section of this summary for more information.)
Graft-versus-host disease (GVHD) is a major complication of allogeneic transplantation, and the intestinal tract, skin, and liver are commonly affected. Symptoms of gastrointestinal GVHD include nausea and vomiting, severe abdominal pain and cramping, and watery, green diarrhea. The volume of accompanying GVHD-associated diarrhea may reach up to 10 L per day and is an indicator of the degree and extent of mucosal damage. Acute GVHD is usually manifested within 100 days posttransplant, although it can occur as early as 7 to 10 days posttransplant. It may resolve or develop into a chronic form requiring long-term treatment and dietary management.
Table 2. Possible Contributions to Diarrhea in Cancer
|Medullary carcinoma of the thyroid|
|Pancreatic cancer, particularly islet cell tumors (Zollinger-Ellison syndrome)|
|Surgery- or procedure-related||Celiac plexus block|
|Gastrectomy, pancreaticoduodenectomy (Whipple procedure)|
|Intestinal resection (malabsorption due to short bowel syndrome)|
|Chemotherapy-related[19,20,21]||Capecitabine, cisplatin, cytosine arabinoside, cyclophosphamide, daunorubicin, docetaxel, doxorubicin, 5-fluorouracil, interferon, irinotecan, leucovorin, methotrexate, oxaliplatin, paclitaxel, topotecan, lapatinib|
|Radiation therapy–related (refer to theRadiation Enteritissection of this summary for more information)[22,23]||Irradiation to the abdomen, para-aortics, lumbar, and pelvis|
|Bone marrow transplantation–related||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||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)|