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Bowel Cancer Symptoms

Irritable bowel syndrome (IBS) is a common functional gastrointestinal (GI) disorder characterized by abdominal pain or discomfort and altered bowel function that affects up to 20% of the North American population; women are twice as likely as men to be affected. (1) IBS is clinically categorized into 3 subtypes--IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), and IBS with alternating diarrhea and constipation (IBS-A).

Epidemiology/prevalence

Traditionally, IBS has been considered a disorder of the nongeriatric (<65 years) population. Patients usually experience symptoms in their teens and 20s and most commonly present to a clinician with symptoms between ages 30 and 50. (2) Although only about 10% of IBS patients are diagnosed after age 60, (3) studies indicate that between 10% and 20% of older persons in the general U.S. population have symptoms consistent with an IBS diagnosis. (3)

Reduced pain perception due to age has been offered as one explanation for the lower prevalence of IBS among older adults. (2) However, despite a poorly defined prevalence, IBS clearly is an important problem for geriatricians to consider. (2,3)

IBS impact

As with younger patients, functional bowel disorders have adverse effects on quality of life in older patients. In a study of 704 subjects from a randomly selected sample of 1,174 Olmsted County residents age 65 and older, patients with IBS (n=73) had significantly lower health-related quality-of-life scores on all scales (physical, role, and social functioning; mental health; health perception; and pain) of the Medical Outcomes Short Form General Health Survey (SF-36) when compared with age-matched controls. (4)

Diagnosis

Because no specific markers can confirm the diagnosis of IBS, symptom-based criteria have been developed to standardize this diagnosis. (1) These criteria are primarily used in research studies for subject inclusion. Their usefulness in the clinical setting, particularly in the geriatric population, remains uncertain. The Manning (5) and the Rome I (6) diagnostic criteria have been used and analyzed in multiple patient populations in the clinical setting. (5-7) Both offer the highest probability of correctly establishing a diagnosis of IBS in persons younger than age 40. (7) The most recently revised criteria, Rome II, are shown in the table. (1)

IBS is typically diagnosed after a clinical history, including symptom assessment for Rome II criteria, and a comprehensive physical examination. It is important for the clinician to assess the presence of any factors that suggest increased risk for organic disease when assessing patient history, physical examination, and laboratory testing. These "red flags" include, but are not limited to, patients age 50 or older, anemia, persistent fever, chronic severe diarrhea, and family history of colon cancer or inflammatory bowel disease (IBD). By definition, therefore, all older patients presenting with symptoms of IBS have at least 1 red flag (age) and require further diagnostic testing, including, but not limited to, a colonoscopy. (1)

Differential diagnosis

Several GI diseases affecting older adults are characterized by symptoms similar to those experienced with IBS. Because the prevalence of advanced neoplasia (high-grade dysplasia or colorectal cancer) continues to increase with age, (8) the exclusion of this and other organic diseases when IBS-like symptoms are present becomes increasingly important as the patient population ages. (2,3) For example, 90% of colorectal cancers occur in persons over age 50, with 23% to 40% of all colorectal cancers occurring in patients age 80 or older. (2)

Older patients have an increased prevalence of other GI conditions, such as colonic diverticulosis (ranging from asymptomatic diverticulosis to diverticulitis), which some clinicians suggest may mimic intermittent IBS symptoms. (2,9) Patients with IBS may also suffer from ischemic colitis--the incidence of ischemic colitis has been reported to be approximately 3 times higher in patients with IBS compared with that of the general population. (10) Symptoms of ischemic colitis include rectal bleeding, which is not indicative of IBS and is considered a red flag in patients of any age. (11)

Although considered to be GI diseases of the young, celiac disease (a malabsorption disorder) and IBD (including ulcerative colitis and Crohn's disease), both of which can present with symptoms similar to those of IBS, have been shown to afflict many older persons as well. In fact, IBD may afflict people at any age, although the age-onset curve shows a bimodal distribution with a major peak in the second and third decades of life and a second smaller peak between ages 55 to 65; however, this later peak may include some cases of ischemic colitis. (12) Celiac disease, which commonly presents as anemia,13 has been shown through the use of screening methods (anti-endomysial antibody or transglutaminase) to be more common in all age groups than previously thought, and Crohn's disease and ulcerative colitis have a peak in incidence in persons over age 60. (14)

Prevalence of pelvic outlet disorders increases in women as they age; typical symptoms include a sense of incomplete evacuation and constipation, both of which are symptoms of IBS. (2) Chronic prostatic disease, a condition affecting oldermen, may cause intermittent loose stools, passage of mucus, lower abdominal pain, and a sense of incomplete evacuation. (2) Patients with a history of radiotherapy for pelvic malignancy may develop radiation proctopathy, enteritis, or chronic ischemic injury to the GI tract. Symptoms of radiation proctopathy include rectal bleeding and pain, urgency, and evacuation difficulties. (15)

Other diseases and conditions common in older patients that are associated with GI symptoms include thyroid disorders; diabetes and other endocrinopathies; achlorhydria; ovarian cancer; and small bowel bacterial overgrowth. (2,3,16,17) These diagnoses need to be considered when evaluating an older patient with new-onset IBS-like symptoms.

In addition to being at increased risk for diseases and conditions with symptoms that may mimic those of IBS, older persons take a disproportionate number of self-administered and prescribed medications for a variety of conditions; these drugs may cause or exacerbate constipation or diarrhea. Medication-induced constipation or diarrhea should be considered in older patients with symptoms of IBS-C or IBS-D, respectively, especially those taking multiple medications.

Treatment/management

Non pharmacologic treatment. IBS treatment traditionally involves dietary and lifestyle changes and pharmacologic agents. Increased dietary fiber, a mainstay of therapy for IBS, can cause adverse events that mimic or exacerbate some IBS symptoms (eg, fiber can cause or exacerbate bloating), particularly in older adults. (1,3)

Some patients with IBS report that their symptoms are exacerbated by certain dietary "triggers" (eg, caffeine, milk, artificial sweeteners), although much of the evidence supporting this relationship is largely anecdotal and not specific to geriatric populations. (18-20) Elimination diets may be beneficial to patients with IBS who have food intolerances and/or allergies. (20) A recent study of 150 outpatients with IBS examined the efficacy of food elimination based on the presence of immunoglobulin G (IgG) antibodies. Results showed that patients with IgG antibodies for certain foods experienced a 10% greater reduction in symptom score on elimination diets for those foods for 12 weeks than did patients on a sham diet (p=0.024), indicating that targeted food elimination may be helpful in reducing the symptoms of IBS. (20)

Pharmacologic treatment. Traditional drug therapies for IBS generally target single symptoms (eg, antispasmodics/ anticholinergics for pain; tricyclic antidepressants [TCAs] for pain; antidiarrheals for diarrhea; and laxatives for constipation). Global relief (ie, relief of multiple symptoms of IBS, including abdominal pain or discomfort, bloating, and bowel dysfunction) of IBS symptoms has rarely been demonstrated with these agents.

Although clinical data on the use of pharmacologic agents for the treatment of IBS specifically in older adults are limited, in the absence of specific data, it is reasonable to assume that the responses of older and younger patients with IBS to treatment should be similar. However, it is important to note that adverse effects may be increased with all treatment strategies in the geriatric population. (2) Older adults are particularly vulnerable to adverse effects, including constipation, dry mouth, urinary retention, drowsiness, and exacerbation of narrow-angle glaucoma, associated with the use of anticholinergic agents (antispasmodics), such as dicyclomine and hyoscyamine, and TCAs. These agents can also produce reversible cognitive deterioration, delirium, and behavior disturbances. (2) Older patients with postural instability and gait disorders (estimated to be 8% to 19% of the noninstitutionalized geriatric population) are at increased risk for falls when taking TCAs, and TCAs should be used with caution in patients with cardiac disease. (2)

Newer drugs that target the pathophysiology of IBS include alosetron (Lotronex, GlaxoSmithKline) and tegaserod (Zelnorm, Novartis). These compounds act at specific serotonin (5-HT) receptors. Serotonin plays a critical role in maintaining normal GI tract function (eg, motility, secretion, and sensation)--it initiates motor and secretory reflexes (eg, peristalsis) and such bowel-related sensations as pain and bloating. (21-23) Fourteen serotonin receptor subtypes have been identified to date; however, the 5-H[T.sub.3] and 5-H[T.sub.4] receptor subtypes are the most clinically relevant in relation to the motor, sensory, and secretory functions of the GI tract. (21,22)

Both alosetron and tegaserod have proven more effective than placebo in providing global relief of IBS symptoms in female patients with IBS-D and IBS-C, respectively. (1) These drugs have been studied in large-scale, randomized, placebo-controlled clinical trials (recently reviewed by Brandt et al). (1)

Alosetron. Alosetron, a 5-HT type 3 (5-H[T.sub.3]) receptor antagonist, has been approved for use only in women with severe IBS-D who have not responded to conventional treatment. (24) Due to reports of severe constipation, bowel obstruction, and ischemic colitis, alosetron carries a black box warning and may be prescribed only by physicians who have enrolled in GlaxoSmithKline's Prescribing Program for Lotronex[R].

Postmarketing experience suggests that older patients may be at greater risk for complications of constipation while taking alosetron. (24) Therefore, caution with this drug is advised in geriatric patients and followup is mandatory. For example, in my clinical practice, older patients are started on a single daily dose of 0.5 mg, which is significantly lower than standard dosing for adults (1 mg twice daily).

Tegaserod. Tegaserod, a 5-HT type 4 (5-H[T.sub.4]) receptor agonist, is approved for use in women with IBS-C. (25) Clinical pharmacologic studies of tegaserod administration in healthy older persons have shown that there is no age effect on the pharmacokinetics of tegaserod when allowing for body weight as a covariate.25 Therefore, no dose adjustment is needed in this patient population. (25)

Tegaserod has been associated with headache and mild, transient diarrhea--although diarrhea has recently been added as a warning on the new product label, only a small number of patients (0.04%) described clinically significant diarrhea while taking tegaserod in the clinical trials. (25) Ischemic colitis was also recently added as a precaution in the product label (Novartis Pharmaceuticals), however, no causal relationship has been established. It is important to note that the efficacy of tegaserod beyond 12 weeks has not been studied.

Because alosetron and tegaserod provide global symptom relief, use of these drugs could potentially reduce the occurrence of polypharmacy among older IBS patients.

Conclusion

Although IBS has long been considered a disorder of young and middle-aged patients, it also appears to be common among older adults and has a significant impact on their quality of life. Diagnosis is symptom-based, but can be confounded by the increased prevalence of organic diseases and comorbid conditions in older patients. Diagnostic testing is warranted in all older patients to establish a confident diagnosis of IBS.

Traditionally, management involved dietary and lifestyle changes. Several concomitant medications were often required to control the variety of symptoms experienced by individual patients, adding to polypharmacy in the older patient population. Newer medications that directly target the intestinal pathology of this condition are leading to more effective IBS management in appropriate patient populations, but patients must be monitored carefully for severe adverse reactions.

Table. Rome II diagnostic criteria and supportive symptoms
of Irritable Bowel Syndrome (IBS)

Diagnostic criteria for IBS *

Abdominal pain or discomfort lasting at least 12 weeks (which need not
be consecutive) of the preceding 12 months, and including at least 2
of the 3 following features:

* Relief achieved with defecation

* Onset associated with a change in frequency of stool

* Onset associated with a change in form (appearance) of stool

* In the absence of structural or metabolic abnormalities to explain
the symptoms

Source: Brandt LJ, Bjorkman D, Fennerty MB, et al. Systematic review
on the management of irrtable bowel syndrome in North America. Am J
Gastroenterol 2002; 97(11 Suppl):63-76. Reprinted with permission from
the American College of Gastroenterology.

References

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(4.) O'Keefe EA, Talley NJ, Zinsmeister AR, Jacobsen SJ. Bowel disorders impair functional status and quality of life in the elderly: A population-based study. J Gerontol A Biol Sci Med Sci 1995; 50(4):M184-9.

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(12.) Shapiro W. Inflammatory bowel disease. eMed J 2004; 1-20.

(13.) Ransford RA, Hayes M, Palmer M, Hall MJ. A controlled, prospective screening study of celiac disease presenting as iron deficiency anemia. J Clin Gastroenterol 2002; 35(3):228-33.

(14.) Holt PR. Gastrointestinal diseases in the elderly. Curr Opin Clin Nutr Metab Care 2003; 6(1):41-8.

(15.) Hong JJ, Park W, Ehrenpreis ED. Review article: current therapeutic options for radiation proctopathy. Aliment Pharmacol Ther 2001; 15(9):1253-62.

(16.) Radebold K. Achlorhydria. eMed J 2004; 1-7.

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(19.) Floch MN, Narayan R. Diet in the irritable bowel syndrome. J Clin Gastroenterol 2002; 35(1 Suppl):S45-52.

(20.) Atkinson W Sheldon TA, Shaath N, Whorwell PJ. Food elimination based on the presencee of IgG antibodies in irritable bowel syndrome: A randomised controlled trial. Gut 2004; 53(10):1459-64.

(21.) Ahn J, Ehrenpreis ED. Emerging treatments for irritable bowel syndrome. Expert Opin Pharmacother 2002; 3(1):9-21.

(22.) De Ponti F, Tonini M. Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs 2001; 61(3):317-32.

(23.) Crowell MD. The role of serotonin in the pathophysiology of irritable bowel syndrome. Am J Manag Care 2001; 7(8 Suppl):S252-60.

(24.) Lotronex[R] [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2002.

(25.) Zelnorm[TM] [package insert]. East Hanover, NJ: Novartis Pharmaceuticals; 2002.

Dr. Ehrenpreis is assistant professor of medicine, department of medicine, gastroenterology division, Rush-Presbyterian/St. Luke's Medical Center, Chicago.

Disclosure The author received financial support for this work from Novartis Pharmaceuticals Corporation.

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