Etiology and Pathogenesis

Inflammatory bowel conditions are considered to be autoimmune diseases in which either the antibodies or other defense mechanisms are directed against the body. Theories explaining the etiopathogenesis of IBD have been proposed ever since UC and CD were recognized as the two major forms of the disease. Although the exact causes and mechanisms of tissue damage in IBD have yet to be completely understood, enough progress has been made to accept the following as one valid explanation.⁴¹

IBD is an inappropriate immune response that occurs in genetically susceptible individuals as the result of a complex interaction among environmental factors, microbial factors, and the intestinal immune system. Although these disorders tend to occur in families, no single genetic marker (i.e., histocompatibility antigen) has been identified yet, preventing early identification of susceptible individuals.

The onset and reactivation of disease are trigged by environmental factors that transiently break the mucosal barrier, stimulate immune responses, or alter the balance between beneficial and pathogenic enteric bacteria.¹²⁷ There is a marked overexpression of proinflammatory cytokines such as tumor necrosis factor (TNF) α and increased production of matrix-degrading enzymes by fibroblasts and macrophages, which are likely responsible for the ulceration and fistula formation that occur in CD.⁹³

A growing number of reports have demonstrated a disorder of autonomic function in subgroups of people with functional bowel disorders. Altered autonomic balance (low vagal tone, increased sympathetic activity) may alter visceral perception. Autonomic dysfunction may represent the physiologic pathway, accounting for many of the extraintestinal symptoms and frequent GI problems encountered by people with other disorders such as chronic fatigue and fibromyalgia.¹¹

Almost an endless list of environmental factors has been identified. Smoking is a risk factor for CD but a protective factor for UC.⁴¹ A possible correlation of the onset of disease with life stresses and poor adaptation to those stresses is cited in the majority of literature regarding IBD, but this has not been proved conclusively. More likely, these factors exacerbate the illness but are not a cause of the condition. Autoimmune disorders such as systemic lupus erythematosus and fibromyalgia often accompany IBD.

There is no evidence that classic infectious agents cause IBD; rather, increasing evidence continues to point to an abnormal immune response against the normal enteric flora. Gut inflammation is mediated by cells of the innate as well as adaptive immune systems, with the additional contribution of nonimmune cells, such as epithelial, mesenchymal, and endothelial cells, and platelets.⁴¹

Improved hygiene in developed countries may be another etiologic factor in the development of inflammatory conditions such as IBD. Geographic and ethnic variations in both UC and CD suggest that parasitic worms (helminths) may be an important environmental factor. Helminths alter host mucosal and systemic immunity. They induce mucosal T cells to make regulatory cytokines that have a protective function in the intestines. Improved hygiene may preclude exposure to helminths, effectively removing immune protection against disease from dysregulated inflammation.^48,155

Two features distinguish CD from UC. In CD, a constitutionally weak immune response predisposes to accumulation of intestinal contents that breach the mucosal barrier of the bowel wall, resulting in granuloma formation and chronic inflammation.⁹⁵ The inflammation usually involves all layers of the bowel wall, referred to as transmural inflammatory disease, and the inflammatory process is discontinuous, so that segments of inflamed areas are separated by normal tissue in a skip pattern. The transverse colon is affected in half of all cases; other common sites include the small bowel, ascending or descending colon, and anorectal region.

In UC, the large intestine (colon) is primarily affected, with involvement extending uniformly and continuously, usually starting from the distal part of the rectum.

Inflammation accompanying CD produces thickened, edematous tissue, and chronic inflammation leads to ulcerations, which produce fissures that extend the inflammation into lymphoid tissue. Mesenteric lymph nodes often are enlarged, firm, and matted together. The mesentery is a membranous peritoneal fold attaching the small intestine to the dorsal abdominal wall.

The lesions are granulomatous (epithelioid cells rimmed by lymphocytes) with projections of inflamed tissue surrounded by fibrous scarring narrowing the intestinal lumen (Fig. 16-10). A combination of the granulomas (nodular swelling), ulceration, and fibrosis results in a cobblestone appearance of the mucosal surface of the colon (Fig. 16-11).

Inflammation of the mucosa associated with UC results in small erosions and subsequent ulcerations with eventual abscess formation and necrosis (Figs. 16-12 and 16-13). Destruction of the mucosa causes bleeding, cramping pain, bowel frequency, and large volumes of watery diarrhea owing to decreased absorption and decreased transit time of intestinal contents through the colon.

Clinical Manifestations

Clinically, inflammatory bowel disorders are characterized by recurrent inflammatory involvement of intestinal segments with diverse clinical manifestations, often resulting in a chronic, unpredictable course. Clinical activity associated with IBD may be rated as mild to moderate, moderate to severe, or severe to fulminant. With early and adequate treatment, asymptomatic remission is possible.

The inflammatory phase of IBD begins with low-grade fever, malaise, weight loss, diarrhea, and abdominal cramping or pain. The inflammatory phase may be followed by the obstructive phase with persistent abdominal bloating and pain and distention from the movement of gas through the system. For comparison of specific signs and symptoms, see Table 16-6.

DIAGNOSIS.

Because no specifically distinctive characteristic features or specific diagnostic tests exist, the diagnosis of CD and UC remains one of exclusion based on medical history and clinical presentation.

Diagnostic and monitoring procedures may require a combination of radiographic modalities and other tests such as colonoscopy, barium enema x-ray, fecal occult blood test, and blood testing (e.g., low hemoglobin level may indicate intestinal blood loss). Microscopically, granulomas present in CD (but not present in UC) distinguish CD from UC.

TREATMENT.

Current treatment is directed toward symptomatic relief and control of the disease process on an individual basis. Treatment is directed to minimize toxicity, delay or decrease the likelihood of recurrence, and optimize quality of life. Some treatment measures may include diet and nutrition, symptomatic medications such as antidiarrheals or antispasmodics, or specific drug therapy (e.g., immune modifiers, antibiotics, corticosteroids, aminosalicylates to reduce intestinal or systemic inflammation).

NSAIDs help reduce pain and stiffness associated with enteropathic arthritis but may cause exacerbation of the IBD. Cyclooxygenase-2 (COX-2) inhibitors may be used instead.

People with CD often have relapses; current investigations are looking for better treatments to maintain remission. A broad range of cytokine-based (biologic) therapies directed at the mucosa and enteric flora have been approved by the Food and Drug Administration and are breaking ground in the management of enteropathic arthropathies (e.g., TNF antagonist adalimumab [Humira]) in addition to growth hormone, a new glucocorticoid (budesonide), methotrexate (MTX), and other agents.^135,160

Experimental treatment with intestinal parasitic worms for IBD is under investigation. Helminthic parasites such as Trichuris suis have the ability to down-regulate host immunity, protecting themselves from elimination.^103,119

Exposure to these parasites may keep the immune system in check and prevent it from attacking the intestine in susceptible individuals. Individuals with IBD who have tried this treatment method have been able to reduce the number of or discontinue the medications they were taking. All participants improved without adverse effects, and the parasites were eliminated from the body naturally after several weeks.⁴⁸

Hospitalization may be required in the case of severe, unremitting disease with complications. Surgical resection of the colon, colostomy, or ileostomy may be performed for toxic megacolon or if medical intervention is unsuccessful and complications such as fistula or abscess occur, or for relief of obstruction.

Treatment refractoriness including physiologic resistance to treatment may have its origin in specific individual immunologic peculiarities; researchers are investigating immunologic, biochemical, and clinical parameters to identify a reliable marker predictive of treatment response.⁵⁷

For individuals with CD, the Crohn’s Disease Activity Index (CDAI) calculator is a monitoring tool used to gauge the progress or lack of progress with treatment. It is not a prognostic indicator and does not predict the outcome of the disease. It is designed to help individuals compare their personal situation from one week to the next. It is available on-line at: http://www.ibdjohn.com/cdai/ (accessed May 26, 2007).

Chemoprevention and routine screening colonoscopy are advised for the prevention of colorectal cancer associated with longstanding IBD. Chemoprevention can include aspirin and other NSAIDs, 5-aminosalicylates, ursodeoxycholic acid, and folate supplementation.⁸⁴

PROGNOSIS.

CD is an incurable, chronic, and sometimes debilitating disease with a known increased risk of intestinal cancer, especially in people who develop this condition at a young age (less than 30 years of age). The risk for colorectal cancer is increased with duration of disease, with a 2% incidence of cancer after 10 years, a 9% incidence after 20 years, and a 19% incidence after 30 years of disease. The development of cancer accounts for one third of deaths related to UC.⁸⁴ Remission is possible for individuals who respond well to treatment; some people are able to discontinue the use of ongoing corticosteroids.

Surgical removal of the diseased bowel does not prevent bowel cancer in CD, so screening of stool specimens and periodic colonoscopic examination and biopsy are required for early detection. With proper medical and surgical treatment, the majority of people are able to cope with this disease and its complications. Few people die as a direct consequence of CD. The mortality rate (5% to 10%) increases with the duration of the disease.

Like CD, UC is a chronic, occasionally debilitating disease. However, it can be cured by colon resection, although this is not always the best course of action. The clinical course is variable but recurrent with long periods of remission possible.

Approximately 85% of clients with UC have mild to moderate intermittent disease managed without hospitalization. The remaining 15% demonstrate a full-blown course involving the entire colon, severe diarrhea, and systemic signs and symptoms.

A 20% mortality rate exists during the first 10 years of UC when complications occur. Also as in CD, 10 years of chronic attacks of UC can predispose the colon to metaplastic changes leading to colon cancer, but unlike in CD, in UC removal of the affected bowel can prevent bowel cancer.

Antibiotic-Associated Colitis

Antibiotics can suppress normal GI tract flora, the bacteria usually residing within the lumen of the intestine, thus allowing yeasts and molds to flourish. Other kinds of microorganisms can replace normal GI tract flora suppressed by antibiotic therapy, such as Clostridium difficile, the major cause of colitis in people with antibioticassociated diarrhea. Although nearly all antibiotics have been associated with this syndrome, drugs such as clindamycin, ampicillin, and the cephalosporins commonly are implicated.

C. difficile is not invasive but replaces normal GI tract flora by producing toxins that damage the colonic mucosa. C. difficile toxins compromise the epithelial cell barrier by at least two pathophysiologic pathways involving complex interactions between immune and inflammatory cells.¹¹⁶

The overgrowth of C. difficile causes lesions described as raised, exudative, necrotic, and inflammatory plaques. These plaques attach to the mucosal surface of the small intestine or colon, or both, giving this condition the name pseudomembranous enterocolitis (PMC). When the lesions are restricted to the small intestine, the term pseudomembranous enteritis is applied.

Onset of symptoms (primarily voluminous, watery diarrhea, but also abdominal cramps and tenderness and fever) occurs during early administration or within 4 weeks after the drug has been discontinued. Complications of untreated illness include dehydration with accompanying electrolyte imbalance, perforation, toxic megacolon, and death.

Diagnosis is made by a stool test for C. difficile toxin or other laboratory tests. Discontinuation of the antibiotics is usually enough to relieve symptoms, but antimicrobial agents such as metronidazole or the more expensive vancomycin are prescribed to treat the C. difficile overgrowth.

Supportive measures may include administration of intravenous fluids to correct fluid losses, electrolyte imbalance, and hypoalbuminemia. Recurrence of symptoms is common when treatment is discontinued or in the case of vancomycin-resistant organisms, requiring retreatment, or in some cases, careful medical observation. In severe disease, mortality rates can be as high as 30%.

For further discussion of this topic, see Chapter 8.

Irritable Bowel Syndrome

DIAGNOSIS.

Diagnosis is based on a classic history, as there is no definite objective blood test, x-ray, or other indicator of IBS. Symptom-based criteria have been developed for the diagnosis of IBS and require the presence of abdominal pain or discomfort for 12 or more weeks (they do not have to be consecutive) within the last 12 months, accompanied by at least two of these symptoms:

Other symptoms such as abnormal stool frequency (more than three times per day or less than three times per week); straining, urgency, or feeling of incomplete evacuation; passage of mucus; and a bloated feeling or abdominal distention are also taken into consideration when making the diagnosis.

Sigmoidoscopy often reveals marked spasm and mucus in the colonic lumen and frequently provokes a spontaneous exacerbation of symptoms. Laboratory studies include a complete blood count and stool examination to rule out lactose intolerance and the presence of occult blood, parasites, and pathogenic bacteria. GI tract films may show altered motility without other evidence of abnormalities. Other radiologic modalities may be employed to diagnose this condition.

TREATMENT.

Treatment is aimed at relieving abdominal discomfort, stabilizing bowel habits, and altering underlying causes of the syndrome. Lifestyle changes (especially dietary changes), medications, behavioral counseling, and psychotherapy have been advocated.

Dietary exclusion of milk and milk products may be helpful for those people with lactose intolerance. Increased dietary fiber, use of bulking agents such as psyllium preparations, and avoidance of alcohol, tobacco, gas-producing foods (e.g., cauliflower, cabbage, baked beans, broccoli), and GI stimulants such as caffeinecontaining beverages often are recommended.

Since people with IBS can have a slower intestinal transit time, resulting in constipation, maintaining regular bowel movements is an important part of the management of IBS. Once constipation occurs, getting rid of painful symptoms is difficult. The use of fiber supplements such as polycarbophil (FiberCon), psyllium seed (Metamucil), and increased intake of water and other fluids is advised.

A stress reduction program with a regular program of relaxation techniques and exercise in conjunction with psychotherapy and biofeedback training may be effective for some people. Behavioral therapy is focused on identifying and reducing or eliminating triggers and reducing negative self-talk. Hypnotherapy (hypnosis) can give some control over the muscle activity of the GI tract and the gut’s sensitivity to stress and other influences.¹⁵⁹

Medications may include antianxiety or antidepressant drugs, and anticholinergic agents before meals to help control symptoms. Antidepressants may reduce visceral hypersensitivity at the level of the visceral afferent fibers. The fact that the enteric nervous system and the brain use the same chemicals and hormones may explain why low doses of antidepressants designed to affect the brain can improve certain digestive diseases.

Newer drugs used in IBS management include serotonin-modulating agents that inhibit the action of serotonin (5-hydroxytryptamine or 5-HT) in the gut. Serotonin, a neurotransmitter found in the gut (and in the brain), appears to be a common link involved in GI motility, intestinal secretion, and pain perception.

The GI tract contains approximately 90% to 95% of the body’s serotonin. Serotonin release in the bowel subsequent to bowel distention has been associated with changes in GI motility, secretion, and possibly pain transmission.³⁸ Research continues to search for targeted medications that can be individualized to each person based on his or her particular manifestation of this condition.

Alternative therapy, including peppermint oil (capsule form) and other natural substances (e.g., chamomile, rosemary, valerian, ginger, turmeric), has antispasmodic effects and may relieve cramping. Probiotic treatment with Lactobacillus and Bifidobacterium may help to alter the microbial flora of the intestinal tract and ease the symptoms of IBS.

PROGNOSIS.

IBS is not a life-threatening disorder, and prognosis is good for controlling symptoms through diet, medication, regular physical activity, and stress management. No known relationship exists between IBS and malignancy of the bowel.

Diverticular Disease

See also the section on Meckel’s diverticulum.

DIAGNOSIS.

Barium enema studies show the characteristic diverticula; colonoscopy and sigmoidoscopy also may provide diagnostic information, and a CT scan may sometimes reveal the inflamed colon segment. No specific laboratory tests exist, but results of fecal examination for occult blood may be positive, and anemia may be identified. Stool cultures may be used to exclude bacterial or parasitic infections.

TREATMENT.

Insights on the pathophysiology and mechanisms of neural injury may lead to more specific treatment in the future (e.g., serotonergic agents and neurotrophins), but for now, treatment is directed at relieving symptoms and preventing diverticulitis. This is accomplished primarily through dietary changes with adherence to a high-fiber diet; prevention of constipation with adequate fluid intake, bran, and bulk laxatives; and exercise during periods of remission.

Acute diverticulitis may require antibiotics and complete rest of the colon accomplished by nasogastric tube feedings and parenteral fluid administration until the inflammatory process has been resolved. Bleeding is a rare complication of diverticulosis and usually is self-limited; but in approximately 10% of people with bleeding diverticula, the hemorrhage is severe enough to require hospitalization, blood transfusion, and possible surgical removal of the affected part of the colon and possible temporary colostomy.

PROGNOSIS.

Prognosis is good for the person with known diverticular disease, especially when prevention of diverticulitis is possible by consuming a high-fiber diet, chewing food carefully, and avoiding indigestible foods. If the diverticulum is not blocked and infected or inflamed (diverticulitis), the person may be asymptomatic. If the trapped fecal material (fecaliths) does not liquefy and drain from the diverticulum, diverticulitis develops.

Neoplasms

PREVENTION.

Evidence exists that reductions in colorectal cancer morbidity and mortality can be achieved through detection and treatment of early-stage cancer and the identification and removal of adenomatous polyps, the precursors of colorectal cancer. Lifestyle modifications such as consuming a low-fat diet and quitting smoking are advised for everyone but especially for anyone at increased risk for colorectal cancer.

Regular screening examinations (e.g., annual stool sample test to check for blood, sigmoidoscopy and digital rectal examination every 5 to 10 years) are recommended for adults over 50 years and for younger people with a family history of the disease. Unfortunately, less than half of U.S. adults 50 years old or older have been tested. Current guidelines for screening colonoscopy do not specify an age limit. Questions have been raised about the cost effectiveness and gains in life expectancy for screening people 80 years of age and older.⁹⁰

The American Cancer Society recommends more intensive surveillance for individuals at higher risk for colorectal cancer. These individuals include anyone with a history of adenomatous polyps, personal previous history of curative-intent resection of colorectal cancer, family history (first-degree relative) of colorectal cancer before age 60, personal history of IBD of significant duration, and family history or genetic testing indicating hereditary syndromes such as nonpolyposis colorectal cancer or FAP.¹³⁹

Colonoscopy is the primary screening test, which involves inserting a snakelike scope into the rectum and large bowel to detect tiny polyps before they develop into cancer. The invasive nature of this test prevents participation in the colorectal cancer screening process so that investigators are working to develop alternative screening tests.

Advances in CT technology and computer capabilities have contributed to the development of a new imaging modality for colorectal lesions called CT colonography or virtual colonoscopy. This is a rapid, minimally invasive, and painless procedure in which a tiny probe is inserted just 4 cm into the rectum. This screening technique may not be sensitive enough and does not identify flat lesions at all, requiring continued development of the technology before it can be applied as a standard procedure.^124,141

Alternatively, technology has made it possible to use a tiny camera that can be swallowed for a virtual endoscopy that is less invasive but may not be as complete, since the camera’s field of view is only 140 degrees, leaving some portions of the GI tract in blind spots. Food and other debris also can obscure lesions from view. In rare cases, the vitamin-sized capsule may get obstructed by strictures or other problems within the intestines, requiring surgical removal.

Other preventive strategies include the following^31,86,138:

Cancer chemoprevention (pharmacologic, nutritional supplemental interventions applied before cancer occurrence) is the next step in attempting to inhibit or reverse the tumorigenic process in colorectal cancer, especially the heritable syndromes.^65,126 Nutrients that play a potential role in decreasing the risk of colorectal cancer include antioxidants such as vitamins A, C, and E, which block the formation of oxygen free radicals that damage DNA and trigger malignant transformation of cells. Calcium intake may reduce the colon’s mucosal exposure to carcinogens by binding with bile salts and fatty acids.

Antioxidant supplementation reduces the risk of colonic polyps, a risk factor for colorectal cancer. Folate needed for DNA and ribonucleic acid (RNA) synthesis has been shown to reduce the risk of colon polyps and colon cancer. Understanding the neoplastic events at the molecular level may provide more definitive preventative information in the coming decade.

Individuals at increased risk for colorectal cancer should talk with their physicians about the preventive use of aspirin and NSAIDs, which has shown some promise in preventing colorectal cancer. The mechanism by which these drugs reduce the risk of colorectal cancer is the ability to block angiogenesis in tumors and enhance the effects of chemotherapy and radiation. Another possible mechanism of this benefit is decreased prostaglandin production, achieved through inhibition of COX activity.^92,150

DIAGNOSIS.

Carcinoma of the colon should be suspected in anyone over the age of 40 who presents with occult blood in the stool, iron deficiency anemia, overt rectal bleeding, or alteration in bowel habits, especially if associated with abdominal discomfort or any of the risk factors mentioned earlier. Physical examination of the abdomen to detect liver enlargement and ascites is followed by palpation of appropriate lymph nodes.

Diagnostic procedures include rectal examination, sigmoidoscopy, proctoscopy, colonoscopy with biopsy of lesions, CT scan, and barium enema studies. Virtual colonoscopy (also known as CT colonography), a series of CT images of the intestine, has advanced enough to become sensitive and accurate enough for use with many but not all people.¹¹⁴

Laboratory diagnostic tests may include a screening test for occult fecal blood and a blood test for carcinoembryonic antigen (CEA), detected in some individuals with colorectal carcinoma. CEA is one of the most widely used tumor markers worldwide, primarily in GI cancers, especially colorectal malignancy. It is of little use in detecting early colorectal cancer, but high preoperative concentrations of CEA correlate with adverse prognosis, and serial CEA measurements can detect recurrent cancer in asymptomatic clients.⁴⁵

TREATMENT.

Surgical removal of the tumor is the mainstay of colorectal cancer treatment. Adjuvant chemotherapy may be administered, depending on the results of the staging process, to treat metastatic disease; radiation therapy is helpful for rectal carcinoma. A temporary or permanent colostomy is needed after surgery by some people.

Using the AJCC/TNM staging, stage 0 disease requires local or regional excision of the polyp with wide margins. Stage 1 cancer is treated the same way, but the individual may need bowel resection and reanastomosis. Adjuvant therapy has not been proven effective in improving survival rates compared with surgical excision alone.

Stage 3 disease requires surgical excision and removal and biopsy of regional lymph nodes. Regional metastasis has occurred at this stage, requiring additional regimens of chemotherapy and/or radiation therapy. Stage 4 cancer is accompanied by systemically metastasized disease requiring a more comprehensive treatment regimen to address local, regional, and systemic disease.⁵⁸

Radiation therapy may be given before surgery to reduce the tumor size or alter the malignant cells to prevent tumor survival after surgery. Tumors in the distal rectum may require resection of the entire rectum with subsequent permanent colostomy. Given the link between adenomatous polyps and cancer, emphasis is on prevention through screening for colonic polyps and carcinomas.

The use of monoclonal antibodies (MABs such as cetuximab [Erbitux], bevacizumab [Avastin], panitumumab [Vectibix]) for the treatment of colorectal cancer is under investigation. These MABs bind to vascular endothelial growth factor receptors and prevent the formation of new blood vessels (angiogenesis) supplying a tumor, thus effectively starving tumor cells. MABs may enhance the effects of chemotherapy and enhance radiation-induced apoptosis. Studies are underway to determine the benefits and optimal timing for use in metastatic and nonmetastatic colorectal cancer.^55,87,96 Use of bevacizumab for early-stage colon cancer in phase III clinical trials was stopped in February 2006 after the deaths of four people.

PROGNOSIS.

Colorectal cancer survival is related closely to the clinical and pathologic stage of the disease at diagnosis. Colorectal cancer detected at an asymptomatic phase has a more favorable prognosis compared to later detection. Polyps containing invasive carcinoma represent about 5% of all adenomas. Malignant polyps constitute a form of early carcinoma that can be cured by endoscopic removal. The risk of an unfavorable outcome increases with the presence of lymph node or local metastases or local recurrence.³³

Approximately 65% of cases present with advanced disease. The 5-year survival rate for cancer limited to the bowel wall at the time of diagnosis approaches 90% but drops to 35% to 60% when lymph nodes are involved and less than 10% with metastatic disease to distant organs such as the liver.

Local recurrence can occur if special operative precautions to prevent implantation of malignant cells are not followed. CEA is a marker for recurrent tumor and should be monitored every 6 months to improve survival. Routine follow-up colonoscopy also is recommended.

Obstructive Disease

Anything that reduces the size of the gastric outlet, preventing the normal flow of chyme and delaying gastric emptying, can cause an obstruction of the bowel. Delayed gastric emptying may be secondary to obstruction of the stomach or secondary to an inability to generate effective propulsive forces (peristalsis). Obstruction of the intestines can occur as a result of (1) organic disease, (2) mechanical obstruction, or (3) functional obstruction (Table 16-7).

DIAGNOSIS, TREATMENT, AND PROGNOSIS.

Diagnosis requires differentiation of obstruction from other acute abdominal conditions such as inflammation and perforation of a viscus, renal or gallbladder colic, obstruction from other causes, vascular disease, and torsion of an organ, as occurs with an ovarian cyst. Abdominal radiography is the most useful diagnostic tool, and laboratory findings may reveal electrolyte disturbances associated with vomiting and dehydration.

Supportive care to alleviate pain and symptoms and to facilitate passage of flatus and feces is instituted toward the goals of restoration of bowel function and prevention of surgical intervention. Intestinal intubation (insertion of a tube into the intestinal lumen to decompress the lumen and break up the obstruction) may relieve obstruction without surgery. Complete obstruction of the intestine is surgically resected; immediate surgery is required in the case of intestinal strangulation. Prognosis varies with the underlying cause; strangulation increases the mortality rate to 25%.

DIAGNOSIS.

History and physical examination remain the most important aspects of diagnosis for all types of hernia; there may be a past history of hernia. The diagnosis of umbilical hernia is usually obvious because of protrusion of the umbilicus confirmed by palpation of the involved structures.

Radiographic investigations are important in diagnosing sports hernias, especially to identify osteitis pubis, adductor tenoperiosteal lesions, and symphyseal instability, and to rule out hip osteoarthritis and tumors. A bone scan may be needed to visualize active osteitis pubis, stress fractures, and tenoperiosteal lesions.⁷⁸

MRI may be used to diagnose bone marrow edema about the pubic symphysis (a sign of osteitis pubis), stress fractures, avascular necrosis, labral hip tears, and articular cartilage defects that can accompany a sports hernia.¹⁴⁸

TREATMENT.

Various supports and trusses are available to contain hernias, but these offer only a temporary solution and may not prevent the hernia from getting bigger with associated complications. The use of strapping techniques is not recommended, because the tape used may lead to ulceration of the thin skin covering the hernia and eventual rupture.

Watchful waiting is an acceptable treatment approach for minimally symptomatic inguinal hernias. Delaying surgical repair until symptoms increase is considered safe because acute hernia incarcerations rarely occur.

Surgical repair is the only curative treatment, but it is no longer recommended as preventive repair in all cases. Complications of herniorrhaphy such as cutaneous nerve injury, bleeding, wound infection, chronic pain, and recurrence have led to a rethinking of surgical correction for asymptomatic hernias. Further studies are needed to identify the natural history of inguinal hernias and to identify the best treatment plan.^54,146

When surgical repair is indicated, there are two main methods used: the traditional approach, known as tension repair, and a newer method, the mesh repair. The tension repair uses an open incision to realign the soft tissues and stitch them closed. A mesh patch is stitched over the hernia to strengthen the repair. There is major discomfort postoperatively, and recovery (return to normal function) takes approximately 6 to 8 weeks for the average person.

The mesh repair uses a plastic mesh hernia repair patch that can be inserted laparoscopically. One side of the patch is positioned to lie against the inner abdominal wall and is held in place by pressure from the abdomen. The other (smaller) side patches the outer abdominal wall. Using this three-dimensional patch system distributes the pressure over a larger area, making the repair stronger. The patch also provides a matrix for tissue ingrowth. Recovery is much faster; many individuals are back to normal activity within 10 days.

PROGNOSIS.

Prognosis varies with the type of hernia and accompanying complications. The incidence of incarceration is about 10% in indirect inguinal hernia and 20% in femoral hernia. Umbilical hernia in adults has a high morbidity and mortality associated with incarceration. Open and laparoscopic repairs produce excellent results; the laparoscopic procedure allows earlier return to play for athletes.

Appendicitis

DIAGNOSIS.

Acute appendicitis must be diagnosed early to prevent perforation, abscess formation, and postoperative complications, but the diagnosis is not always easy to make. Although the clinical diagnosis may be straightforward in people who present with classic signs and symptoms, atypical presentations require the physician to differentiate appendicitis from a large variety of GI, genitourinary, and gynecologic conditions.

A careful history and thorough physical examination are the primary diagnostic tools. Rebound tenderness is a widely used physical examination test for clients with suspected appendicitis, but the test can be very uncomfortable for the individual. Some experts no longer advise its use with clients who have abdominal pain but prefer the “pinch-an-inch” test, which is a form of the rebound test in reverse.

To perform the pinch-an-inch test, a fold of abdominal skin over McBurney’s point is grasped and elevated away from the peritoneum. The skin is then allowed to recoil back against the peritoneum. The test is considered positive for peritonitis if there is increased pain when the skin fold strikes the peritoneum (Fig. 16-24).¹

An elevated white blood cell count (more than 20,000/mm³; leukocytosis) suggests ruptured appendix and peritonitis. Urinalysis reveals abnormalities in up to 40% of individuals tested.⁷⁰ Abdominal CT is more diagnostic than ultrasound but is usually only done when a diagn- osis cannot be made.⁷⁰ Histologic examination of the resected appendix is used to confirm the diagnosis.

TREATMENT.

Appendectomy, or surgical removal of the vermiform appendix, is performed as soon as possible. Antibiotics are administered preoperatively to decrease the incidence of postoperative wound infection and intraabdominal abscess.⁷⁰ With accurate diagnosis and early surgical removal, mortality and morbidity rates are less than 1%.

PROGNOSIS.

Prognosis is good unless diagnosis is delayed and perforation occurs (rarely during the first 8 hours of symptomatic presentation). Perforation with complications such as peritonitis, hypovolemia, and septic shock has a poor prognosis. Perforation is more likely in infants under 2 years of age and in adults over 60 years. In up to 20% of individuals who undergo emergency appendectomy, pathologic examination of the tissue shows a normal appendix.⁶⁹

Peritonitis

DIAGNOSIS, TREATMENT, AND PROGNOSIS.

Abdominal films, barium enema, and an abdominal tap may be used in the differential diagnosis of peritonitis. Peritonitis should be treated immediately to control infection; preserve the barrier to further microbial invasion; minimize the effects of paralytic ileus; and correct fluid, electrolyte, and nutritional disorders.

If peritonitis is advanced and surgery is contraindicated because of shock and circulatory failure, oral fluids are prohibited and intravenous fluids are necessary for replacement of electrolyte and protein losses. A long intestinal tube is inserted through the nose into the intestine to reduce pressure within the bowel. Once the infection has become walled off and the client’s condition improves, surgical drainage and repair can be attempted.

Despite treatment with antibiotics, surgical drainage and debridement, and supportive measures, generalized peritonitis is still associated with a mortality rate of 50% and is especially dangerous in the older adult. Individuals recovering from an episode of bacterial peritonitis should be considered as potential candidates for liver transplantation.

Rectal Fissure

A rectal or anal fissure is an ulceration or tear of the lining of the anal canal, usually on the posterior wall. An acute fissure occurs as a result of excessive tissue stretching or tearing, such as childbirth or passage of a large, hard bowel movement through the area. The skin tear is very fragile and tends to reopen easily with the next bowel movement, prompting the person to avoid going to the bathroom for days. Neglecting the “call of the stool” can result in constipation and further exacerbation of the problem, especially in the presence of risk factors for constipation (see the section on Constipation in this chapter).

Anal fissures frequently heal within a month or two when treated with a combination of bran and bulk laxatives or stool softeners, sitz baths, and emollient suppositories. Chronic fissures are usually secondary to a tight rectal sphincter or infectious material retained in the anal sinuses. Sharp pain, followed by burning, accompanies defecation. Other symptoms include mucus, an external skin tag at the anus (sentinel pile), and itching.

Rectal Abscesses and Fistulas

Anal abscesses and fistulas can occur as a result of an infected anal gland, fissure, or prolapsed hemorrhoid and are most common in people with CD. The infection can cause pus, mucus, and blood to drain from the anus. Fistulas (abnormal channels to the body’s surface) may form spontaneously to drain the abscesses. Swelling, pain, and throbbing exacerbated by sitting or walking are the primary symptoms of these conditions, which may heal with time or may be treated with surgical drainage with or without antibiotics.

Hemorrhoids

Hemorrhoids, or piles, are varicose veins of a pillowlike cluster of veins that lie just beneath the mucous membranes lining the lowest part of the rectum and anus. They can be internal or external. Hemorrhoids are fairly common, affecting as many as half of all adults more than 50 years of age. It is hypothesized that the connective tissues that support and hold hemorrhoids in place can weaken with age, causing hemorrhoids to bulge and prolapse.

This condition is associated especially with anything that increases intraabdominal pressure (see Box 16-1), such as chronic constipation, pregnancy (the enlarged uterus presses on the veins), pelvic congestion or pelvic venous disease, congestive heart failure, prolonged sitting or standing, low-fiber diet, obesity, diarrhea, and delaying a bowel movement when the urge presents itself.

Higher resting anal canal tone may also contribute to the development of hemorrhoids. The smooth muscle of the anal canal tends to be tighter than average, even when not straining. Constipation and straining add to the pressure in the anal canal.

Internal hemorrhoids occur in the lower rectum and usually are noticed first when a small amount of bleeding occurs during passage of stool, especially if straining occurs during a bowel movement. Internal hemorrhoids are asymptomatic (rectal tissue lacks nerve fibers) except in the presence of an anal fissure, thrombosis, or strangulation of the varicose vein. In the case of strangulation, straining can cause an internal hemorrhoid to protrude (prolapse) from the anus. The blood supply is cut off by the anal sphincter, causing local discomfort and possible itching. This can result in thrombosis when blood within the hemorrhoid clots.

Internal hemorrhoids may require ligation, sclerosing, laser surgery, or cryosurgery to destroy the affected tissue. In the case of advanced chronic hemorrhoids, recurrent bleeding and anemia may necessitate surgery (hemorrhoidectomy, stapled hemorrhoidopexy).

External hemorrhoids located under the skin around the anus bleed (bright red blood) if the hemorrhoid is injured or ulcerated and are very painful because they form in nerve-rich tissue outside the anal canal. Other manifestations include pressure, rectal itching, irritation, and a palpable mass. Severe bleeding or mild bleeding repeatedly from prolonged trauma to the vein during defecation can cause iron-deficiency anemia.

External hemorrhoids can be treated with local application of topical medications, sitz baths, high-fiber diet, and avoidance of constipation and other causes of increased intraabdominal pressure. A stool softener or psyllium preparation may be used when a modified diet is unsuccessful in eliminating constipation. Local topical preparations for hemorrhoids are used to reduce pain or itching. In addition, moderate aerobic exercise such as brisk walking 20 to 30 minutes daily can help stimulate bowel function,

1. Adams, BD. Pinch-an-inch test for appendicitis. South Med J. 2005;98(12):1207–1209.

2. Agency for Health Care Policy and Research (AHCPR) Colorectal cancer screening: summary, 2001. Available on-line at http://www.ahcpr.gov Accessed April 26, 2008.

3. Ahuja, A, Brent, L. Revisting the spondyloarthropathies: a new era of treatment. J Musculoskelet Med. 2006;23(9):654–666.

4. Aldoori, WH, Giovannucci, EL, Rimm, EB, et al. Use of acetaminophen and nonsteroidal antiinflammatory drugs: a prospective study and the risk of symptomatic diverticular disease in men. Arch Fam Med. 1998;7(3):262–263.

5. Ali, A, Toner, BB, Stuckless, N, et al. Emotional abuse, self-blame, and self-silencing in women with irritable bowel syndrome. Psychosom Med. 2000;62(1):76–82.

6. American Cancer Society (ACS) Statistics for 2007: cancer facts and figures for African Americans 2007-2008. Available on-line at www.cancer.org Accessed May 28, 2007.

7. American Physical Therapy Association (APTA). Guidelines for recognizing and providing care for victims of domestic violence. Alexandria, VA: APTA, 1997. [No. P-138].

8. Anderson, M, Robinson, M. Watching for-and managing-joint problems in inflammatory bowel disease. J Musculoskelet Med. 1996;13(11):28–34.

9. Aviles, A. The role of surgery in primary gastric lymphoma: results of a controlled clinical trial. Ann Surg. 2004;240(1):44–50.

10. Aviles, A. Surgery and chemotherapy versus chemotherapy as treatment of high-grade MALT gastric lymphoma. Med Oncol. 2006;23(2):295–300.

11. Befus, AD, Mathison, R, Davison, J. Integration of neuro-endocrine immune responses in defense of mucosal surfaces. Am J Trop Med Hyg. 1999;60(4):26–34.

12. Best, WR. Development of a Crohn’s disease activity index. Gastroenterology. 1976;70(3):439–444.

13. Blomhoff, S, Spetalen, S, Jacobsen, MB, et al. Intestinal reactivity to words with emotional content and brain information processing in irritable bowel syndrome. Dig Dis Sci. 2000;45(6):1160–1165.

14. Blomhoff, S, Spetalen, S, Jacobsen, MB, et al. Rectal tone and brain information processing in irritable bowel syndrome. Dig Dis Sci. 2000;45(6):1153–1159.

15. Breusch, SJ. Acute pseudo-obstruction of the colon following left-sided total hip replacement. Int J Clin Pract. 1997;51(5):327–329.

16. Brown, C. Electrical stimulation for fecal incontinence following bowel resection. Rehab Oncol. 2001;19(3):20.

17. Brown, LM. Helicobacter pylori: epidemiology and routes of transmission. Epidemiol Rev. 2000;22(2):283–297.

18. Burdick, JS. Esophageal cancer prevention, cure, and palliation. Semin Gastrointest Dis. 2000;11(3):124–133.

19. Camilleri, M, Lee, JS, Viramontes, B, et al. Insights into the pathophysiology and mechanisms of constipation, irritable bowel syndrome, and diverticulosis in older people. J Am Geriatr Soc. 2000;48(9):1142–1150.

20. Camilleri, M, Spiller, R. Irritable bowel syndrome: diagnosis and treatment. Edinburgh: Saunders, 2002.

21. Campbell-Thompson, M, Lynch, IJ, Bhardwaj, B. Expression of estrogen (ER) subtypes and ERbeta isoforms in colon cancer. Cancer Res. 2001;61(2):632–640.

22. Cassara, JE, Shaheen, NJ. Endoscopic anti-reflux devices: a year of challenges and change. Curr Opin Gastroenterol. 2006;22(4):423–428.

23. Centers for Disease Control and Prevention (CDC). Hypertrophic pyloric stenosis in infants following pertussis prophylaxis with erythromycin. JAMA. 2000;283(4):471–472.

24. Chao, A. Meat consumption and risk of colorectal cancer. JAMA. 2005;293(2):233–234.

25. Cheng, Y, Macera, CA, Davis, DR, et al. Does physical activity reduce the risk of developing peptic ulcers? Br J Sports Med. 2000;34(2):116–121.

26. Chermesh, I, Eliakim, R. Probiotics and gastrointestinal tract: where are we in 2005? World J Gastroenterol. 2006;12(6):853–857.

27. Christensen, J. Hypothesis: how might oesophagitis cause hiatus hernia? Neurogastroenterol Motil. 2003;15(5):567–569.

28. Christensen, J, Miftakhov, R. Hiatus hernia: a review of evidence for its origin in esophageal longitudinal muscle dysfunction. Am J Med. 2000;108(suppl 4a):3S–7S.

29. Clark, TJ, McKenna, LS, Jewell, MJ. Physical therapists’ recognition of battered women in clinical settings. Phys Ther. 1996;76(1):12–19.

30. Clarke, HD. Acute pseudo-obstruction of the colon as a postoperative complication of hip arthroplasty. J Bone Joint Surg Am. 1997;79:1642–1647.

31. Colbert, LH, Hartman, TJ, Malila, N, et al. Physical activity in relation to cancer of the colon and rectum in a cohort of male smokers. Cancer Epidemiol Biomarkers Prev. 2001;10(3):265–268.

32. Cole, RP. Functional recovery in cancer rehabilitation. Arch Phys Med Rehabil. 2000;81(5):623–627.

33. Compton, CC, Greene, FL. The staging of colorectal cancer: 2004 and beyond. CA Cancer J Clin. 2004;54(6):295–308.

34. Cremonini, F. Irritable bowel syndrome: epidemiology, natural history, health care seeking and emerging risk factors. Gastroenterol Clin North Am. 2005;34(2):189–204.

35. Crew, KD. Epidemiology of upper gastrointestinal malignancies. Semin Oncol. 2004;31:450–464.

36. Crocker, JA, Gudas, SA. Rehabilitation referral patterns in colorectal carcinoma. Rehab Oncol. 2005;23(3):17–21.

37. Crohn’s and Colitis Foundation of America (CCFA) Questions and answers about Crohn’s disease and ulcerative colitis, 2001. Available on-line at http://www.ccfa.org Accessed April 26, 2008.

38. Crowell, MD. The role of serotonin in the pathophysiology of irritable bowel syndrome. Am J Manag Care. 2001;7(suppl 8):S252–S260.

39. Cunningham-Rundles, S, Lin, DH. Nutrition and the immune system of the gut. Nutrition. 1998;14(7-8):573–579.

40. Dahshan, A. Helicobacter pylori and infantile hypertrophic pyloric stenosis: is there a possible relationship? J Pediatr Gastroenterol Nutr. 2006;42(3):262–264.

41. Danese, S. Etiopathogenesis of inflammatory bowel disease. World J Gastroenterol. 2006;12(30):4807–4812.

42. de la Chapelle, A. Genetic predisposition to colorectal cancer. Nat Rev Cancer. 2004;4(10):769–780.

43. De Lillo, AR, Rose, S. Functional bowel disorders in the geriatric patient: constipation, fecal impaction, and fecal incontinence. Am J Gastroenterol. 2000;95(4):901–905.

44. Dean, E. Oxygen transport deficits in systemic diseases and implications for physical therapy. Phys Ther. 1997;77(2):187–202.

45. Duffy, MJ. Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful? Clin Chem. 2001;47(4):624–630.

46. Duggan, JM. Systematic review: the liver in coeliac disease. Aliment Pharmacol Ther. 2005;21(5):515–518.

47. Easterling, C. Attaining and maintaining isometric and isokinetic goals of the Shaker exercise. Dysphagia. 2005;20(2):133–138.

48. Elliott, DE. Helminths as governors of immune-mediated inflammation. Int J Parasitol. 2007;37(5):457–464.

49. elMaraghy, AW. Ogilvie’s syndrome after lower extremity arthroplasty. Can J Surg. 1999;42(2):133–137.

50. Falk, GW. Barrett’s esophagus. Gastroenterology. 2002;122:1569–1591.

51. Fasano, A. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med. 2003;163(3):286–292.

52. Feldman, M, Peptic ulcer disease. ACP Medicine. New York: WebMD; 2004. Available on-line at www.medscape.com/viewarticle/494030 Accessed May 25, 2007.

53. Ferdjallah, M, Wertsch, JJ, Shaker, R. Spectral analysis of surface electromyography (EMG) of upper esophageal sphincter-opening muscles during head lift exercise. J Rehabil Res Dev. 2000;37(3):335–340.

54. Fitzgibbons, RJ, Jr. Watchful waiting vs. repair of inguinal hernia in minimally symptomatic men: a randomized clinical trial. JAMA. 2006;295(3):285–292.

55. Food and Drug Administration (FDA). FDA approves drugs for colorectal, lung cancer. FDA Consum. 2007;41(1):5.

56. Gaspar, LE, Winter, K, Kocha, WI, et al. A phase I/II study of external beam radiation, brachytherapy, and concurrent chemotherapy for patients with localized carcinoma of the esophagus (Radiation Therapy Oncology Study Group 9207): final report. Cancer. 2000;88(5):988–995.

57. Gelbmann, CM. Prediction of treatment refractoriness in ulcerative colitis and Crohn’s disease-do we have reliable markers? Inflamm Bowel Dis. 2000;6(2):123–131.

58. Gersh, MR. Physical therapy implications for clients with colorectal cancer. Rehab Oncol. 2004;22(3):15–22.

59. Gershon, MD. The second brain: the scientific basis of gut instinct and a groundbreaking new understanding of nervous disorders of the stomach and small intestine. New York: HarperCollins, 1998.

60. Goodman, CC, Snyder, TE. Differential diagnosis in physical therapy, ed 3. Philadelphia: Saunders, 2000.

61. Goodwin, RD, Stein, MB. Generalized anxiety disorder and peptic ulcer disease among adults in the United States. Psychosom Med. 2002;64(6):862–866.

62. Gow, PJ, Chapman, RW. Modern management of oesophageal varices. Postgrad Med J. 2001;77(904):75–81.

63. Green, JA, Amaro, R, Barkin, JS. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. Dig Dis Sci. 2000;45(12):2367–2368.

64. Harrington, KL, Haskvitz, EM. Managing a patient’s constipation with physical therapy. Phys Ther. 2006;86(11):1511–1519.

65. Hawk, E, Lubet, R, Limburg, P. Chemoprevention in hereditary colorectal cancer syndromes. Cancer. 1999;86(11 suppl):2551–2563.

66. Hegab, AM, Luketic, VA. Bleeding esophageal varices: how to treat this dreaded complication of portal hypertension. Postgrad Med. 2001;109(2):75–76. [81-86, 89].

67. Heitkemper, M. Overlapping conditions in women with irritable bowel syndrome. Urol Nurs. 2005;25(1):25–31.

68. Higgins, PDR. Epidemiology of constipation in North America: a systematic review. Am J Gastroenterol. 2004;99:750–759.

69. Hong, JJ. A prospective randomized study of clinical assessment versus computed tomography for the diagnosis of acute appendicitis. Surg Infect (Larchmt). 2003;4(3):231–239.

70. Humes, DJ. Acute appendicitis. BMJ. 2006;333(7567):530–534.

71. Inadomi, JM. Screening and surveillance for Barrett esophagus in high-risk groups: a cost-utility analysis. Ann Intern Med. 2003;138:176–186.

72. Iqbal, A. Endoscopic therapies of gastroesophageal reflux disease. World J Gastroenterol. 2006;12(17):2641–2655.

73. Jemal, A. Cancer statistics, 2007. CA Cancer J Clin. 2007;57(1):43–66.

74. Johns Hopkins Medical Letter. Do you need a B12 boost? Johns Hopkins Med Lett. 1998;10(4):6.

75. Johnson, C. Handling the hurt: physical therapy and domestic violence. Phys Ther. 1997;5(1):52–64.

76. Kang, W, Kudsk, KA. Is there evidence that the gut contributes to mucosal immunity in humans? JPEN J Parenter Enteral Nutr. 2007;31(3):246–258.

77. Kauffman, D. Postoperative outcomes for patients with colon cancer: laparoscopy-assisted vs. open colostomy. Rehab Oncol. 2003;21(2):18–20.

78. Kemp, S, Batt, ME, The “sports hernia”: a common cause of groin pain. Phys Sports Med. 1998;26(1). Available on-line at http://www.physsportsmed.com/issues/1998/01jan/batt.htm. Accessed May 21, 2007.

79. Khoury, RM, Camacho-Lobato, L, Katz, PO, et al. Influence of spontaneous sleep positions on nighttime recumbent reflux in patients with gastroesophageal reflux disease. Am J Gastroenterol. 1999;94(8):2069–2073.

80. Kluin, J. Endoscopic evaluation and treatment of groin pain in the athlete. Am J Sports Med. 2004;32(4):944–949.

81. Koffler, KH. Strength training accelerates gastrointestinal transit in middle-aged and older men. Med Sci Sports Exerc. 1992;24:415–419.

82. Koloski, NA. Predictors of health care seeking for irritable bowel syndrome: a critical review of the literature on symptom and psychosocial factors. Am J Gastroenterol. 2001;96(5):1340–1349.

83. Kountouras, J, Boura, P, Lygidakis, NJ. New concepts of molecular biology for colon carcinogenesis. Hepatogastroenterology. 2000;35:1291–1297.

84. Krok, KL. Colorectal cancer in inflammatory bowel disease. Curr Opin Gastroenterol. 2004;20(1):43–48.

85. Kumar, A. Results of inguinal canal repair in athletes with sports hernia. J R Coll Surg Edinb. 2002;47(3):561–565.

86. Kushi, LH. American Cancer Society guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin. 2006;56(5):254–281.

87. Labianca, R. Development and clinical indications of cetuximab. Int J Biol Markers. 2007;22(suppl 4):S40–46.

88. Lanza, E. High dry bean intake and reduced risk of advanced colorectal adenoma recurrence among participants in the polyp prevention trial. J Nutr. 2006;136(7):1896–1903.

89. Lembo, A. Current concepts: chronic constipation. N Engl J Med. 2003;349:1360–1368.

90. Lin, OS. Screening colonoscopy in very elderly patients: prevalence of neoplasia and estimated impact on life-expectancy. JAMA. 2006;295(20):2357–2365.

91. Lucak, S, Diagnosis irritable bowel syndrome. MedGenMed. 2004;6(1). Available on-line at www.medscape.com/viewarticle/465760 Accessed May 26, 2007.

92. Lynch, PM. COX-2 inhibition in clinical cancer prevention. Oncology. 2001;15(3 suppl 5):21–26.

93. MacDonald, TT. Immunopathogenesis of Crohn’s disease. J Parenter Enteral Nutr. 2005;29(4 suppl):S118–S124.

94. Maheshwai, N. Are young infants treated with erythromycin at risk for developing hypertrophic pyloric stenosis? Arch Dis Child. 2007;92(3):271–273.

95. Marks, DJB. Defective acute inflammation in Crohn’s disease: a clinical investigation. Lancet. 2006;367(9511):668–678.

96. Marshall, JL. Bevacizumab in the treatment of colorectal cancer. Clin Adv Hematol Oncol. 2007;5(1 suppl 1):8–9.

97. Mayne, ST. Diet, obesity, and reflux in the etiology of adenocarcinomas of the esophagus and gastric cardia in humans. J Nutr. 2002;132:3467S–3470S.

98. Meshkinpour, H. Effects of regular exercise in management of chronic idiopathic constipation. Dig Dis Sci. 1998;43:2379–2383.

99. Montalto, M. Management and treatment of lactose malabsorption. World J Gastroenterol. 2006;12(2):187–191.

100. Morbidity and Mortality Weekly Report (MMWR). Diagnosis and management of foodborne illnesses. MMWR Recomm Rep. 2001;50(RR-2):1–69.

101. Morbidity and Mortality Weekly Review (MMWR). Diagnosis and management of foodborne illnesses: a primer for physicians and other health care professionals. MMWR Recomm Rep. 2004;53(RR-4):1–33.

102. Morbidity and Mortality Weekly Report (MMWR), Preliminary FoodNet data on the incidence of foodborne illnesses-selected sites, United States, 2000. MMWR Morb Mortal Wkly Rep. 2001;50(13):241–246. Available on-line at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5304a1.htm Accessed May 22, 2007.

103. Moreels, TG, Pelckmans, PA. Gastrointestinal parasites: potential for refractory inflammatory bowel diseases. Inflamm Bowel Dis. 2005;11(2):178–184.

104. Morgner, A, Bayerdorffer, E, Neubauer, A, et al. Gastric MALT lymphoma and its relationship to Helicobacter pylori infection: management and pathogenesis of the disease. Microsc Res Tech. 2000;48(6):349–356.

105. Mort, JR. Interaction between selective serotonin reuptake inhibitors and nonsteroidal antiinflammatory drugs: review of the literature. Pharmacotherapy. 2006;26(9):1307–1313.

106. Murphy, TV, Gargiullo, PM, Massoudi, MS, et al. Intussusception among infants given an oral rotavirus vaccine. N Engl J Med. 2001;344(8):564–572.

107. Nagura, H, Ohtani, H, Sasano, H, et al. The immuno-inflammatory mechanism for tissue injury in inflammatory bowel disease and Helicobacter pylori-infected chronic active gastritis: roles of the mucosal immune system. Digestion. 2001;63(suppl 1):12–21.

108. Nakatsuchit, T. The necessity of chest physical therapy for thorascopic esophagectomy. J Int Med Res. 2005;33(4):434–441.

109. Nelson, JD. Acute colonic pseudo-obstruction (Ogilvie syndrome) after arthroplasty in the lower extremity. J Bone Joint Surg Am. 2006;88(3):604–610.

110. Oliveria, SA, Christos, PJ, Talley, NJ, et al. Heartburn risk factors, knowledge, and prevention strategies: a population-based survey of individuals with heartburn. Arch Intern Med. 1999;159(14):1592–1598.

111. Overmier, JB, Murison, R. Anxiety and helplessness in the face of stress predisposes, precipitates, and sustains gastric ulceration. Behav Brain Res. 2000;110(1-2):161–174.

112. Pahor, M, Guralnik, JM, Salive, ME, et al. Physical activity and risk of severe gastrointestinal hemorrhage in older persons. JAMA. 1994;272:595–599.

113. Paulozzi, LJ. Is Helicobacter pylori a cause of infantile hypertrophic pyloric stenosis? Med Hypotheses. 2000;55(2):119–125.

114. Pickhardt, PJ. CT colonography (virtual colonoscopy): a practical approach for population screening. Radiol Clin North Am. 2007;45(2):361–375.

115. Pilotto, A. Recent advances in the treatment of GERD in the elderly: focus on proton pump inhibitors. Int J Clin Pract. 2005;59(10):1204–1209.

116. Pothoulakis, C, Lamont, JT. Microbes and microbial toxins: paradigms for microbial-mucosal interactions: II. The integrated response of the intestine to Clostridium difficile toxins. Am J Physiol Gastrointest Liver Physiol. 2001;280(2):G178–G183.

117. Potosky, AL. Age, sex, and racial differences in the use of standard adjuvant therapy for colorectal cancer. J Clin Oncol. 2002;20:1192–1202.

118. Quigley, EM, Quera, R. Small intestinal bacterial overgrowth: roles of antibiotics, prebiotics, and probiotics. Gastroenterology. 2006;130(2 suppl 1):S78–S90.

119. Reddy, A, Fried, B. The use of Trichuris suis and other helminth therapies to treat Crohn’s disease. Parasitol Res. 2007;100(5):921–927.

120. Reilly, J, Baker, GA, Rhodes, J, et al. The association of sexual and physical abuse with somatization: characteristics of patients presenting with irritable bowel syndrome and non-epileptic attack disorder. Psychol Med. 1999;29(2):399–406.

121. Reis, LAG. The annual report to the nation on the status of cancer with a special section on colorectal cancer. Cancer. 2000;88:2398–2424.

122. Romano, M, Cuomo, A, Eradication of Helicobacter pylori: a clinical update. MedGenMed. 2004;6(1). Available on-line at http://www.medscape.com/viewarticle/468006. Accessed May 26, 2007.

123. Rose, SJ, Rothstein, JM. Muscle mutability: general concepts and adaptations to altered patterns of use. Phys Ther. 1982;62:1773.

124. Rubin, DT, Dachman, AH. Virtual colonoscopy: a novel imaging modality for colorectal cancer. Curr Oncol Rep. 2001;3(2):88–93.

125. Saito, YA. The epidemiology of irritable bowel syndrome in North America: a systematic review. Am J Gastroenterol. 2002;97(8):1910–1915.

126. Sandler, RS, Halabi, S, Kaplan, EB, et al. Use of vitamins, minerals, and nutritional supplements by participants in a chemoprevention trial. Cancer. 2001;91(5):1040–1045.

127. Sartor, RB. Mechanisms of disease: pathogenesis of Crohn’s disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol. 2006;3(7):390–407.

128. Schatzkin, A. Dietary fiber and whole-grain consumption in relation to colorectal cancer in the NIH-AARP Diet and Health Study. Am J Clin Nutr. 2007;85(5):1353–1360.

129. Schatzkin, A, Lanza, E, Corle, D, et al. Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas, Polyp Prevention Trial Study Group. N Eng J Med. 2000;342(16):1149–1155.

130. Schoon, EJ, Blok, BM, Geerling, BJ, et al. Bone mineral density in patients with recently diagnosed inflammatory bowel disease. Gastroenterology. 2000;119(5):1203–1208.

131. Schoon, EJ, Muller, MC, Vermeer, C, et al. Low serum and bone vitamin K status in patients with longstanding Crohn’s disease: another pathogenetic factor of osteoporosis in Crohn’s disease? Gut. 2001;48(4):448.

132. Schulte, CM, Dignass, AU, Goebell, H, et al. Genetic factors determine extent of bone loss in inflammatory bowel disease. Gastroenterology. 2000;119(4):909–920.

133. Semrad, CE. Bone mass and gastrointestinal disease. Ann N Y Acad Sci. 2000;904:564–570.

134. Serebruany, VL. Selective serotonin reuptake inhibitors and increased bleeding risk. Am J Med. 2006;119(2):113–116.

135. Shanahan, F. Inflammatory bowel disease: immunodiagnostics, immunotherapeutics, and ecotherapeutics. Gastroenterology. 2001;120(3):622–635.

136. Sherwood, W. Infantile hypertrophic pyloric stenosis: an infectious cause? Pediatr Surg Int. 2007;23(1):61–63.

137. Silano, M. Delayed diagnosis of coeliac disease increases cancer risk. BMC Gastroenterol. 2007;7:8.

138. Slattery, ML. Physical activity and colon cancer: a public health perspective. Ann Epidemiol. 1997;7:137–145.

139. Smith, RA. American Cancer Society guidelines for the early detection of cancer, 2006. CA Cancer J Clin. 2006;56(1):11–15.

140. Souza, RF, Spechler, SJ. Concepts in the prevention of adenocarcinoma of the distal esophagus and proximal stomach. CA Cancer J Clin. 2005;55(6):334–351.

141. Spinzi, G, Belloni, G, Martegani, A, et al. Computed tomographic colonography and conventional colonoscopy for colon diseases: a prospective blinded study. Am J Gastroenterol. 2001;96(2):394–400.

142. Stephen, AE. Shortened length of stay and hospital cost reduction with implementation of an accelerated clinical care pathway after elective colon resection. Surgery. 2003;133:277–282.

143. Storm-Dickerson, TL. What have we learned over the past 20 years about appendicitis in the elderly? Am J Surg. 2003;185(3):198–201.

144. LStrate, Can diverticular disease patients eat nuts, corn, and popcorn? Presentation at Digestive Diseases Week Annual Meeting, Washington, DC, May 22, 2007.

145. Streitz, JM, Jr. Endoscopic surveillance of Barrett’s esophagus: does it help? J Thorac Cardiovasc Surg. 1993;105:383–387.

146. Stroupe, KT. Tension-free repair versus watchful waiting for men with asymptomatic or minimally symptomatic inguinal hernias. J Am Coll Surg. 2006;203(4):458–468.

147. Sutton, P. Helicobacter pylori vaccines and mechanisms of effective immunity: is mucus the key? Immunol Cell Biol. 2001;79(1):67–73.

148. Swan, KG, Wolcott, M. The athletic hernia. Clin Orthop Rel Res. 2006;455:78–87.

149. Tam, WC. Impact of endoscopic suturing of the gastroesophageal junction on lower esophageal sphincter function and gastroesophageal reflux in patients with reflux disease. Am J Gastroenterol. 2004;99(2):195–202.

150. Vainio, H, Bianchini, F. Prevention of disease with pharmaceuticals. Pharmacol Toxicol. 2001;88(3):111–118.

151. Van Veen, RN. Successful endoscopic treatment of chronic groin pain in athletes. Surg Endosc. 2007;21(2):189–193.

152. Vanagunas, A. Managing gastrointestinal problems in athletes. J Musculoskel Med. 1999;16(7):405–415.

153. Ward, EM. Barrett’s esophagus is common in older men and women undergoing screening colonoscopy regardless of reflux symptoms. Am J Gastroenterol. 2006;101(1):12–17.

154. Weinryb, RM. Psychological factors in irritable bowel syndrome: a population-based study of patients, non-patients and controls. Scand J Gastroenterol. 2003;38(5):503–510.

155. Weinstock, JV. Helminths and mucosal immune modulation. Ann N Y Acad Sci. 2006;1072:356–364.

156. Wessinger, S. Increased use of selective serotonin uptake inhibitors in patients admitted with gastrointestinal hemorrhage: a multicenter retrospective analysis. Aliment Pharmacol Ther. 2006;23(7):937–944.

157. Whitehead, WE. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? Gastroenterology. 2002;122(4):1140–1156.

158. Wijnhoven, BP, Tilanus, HW, Dinjens, WN. Molecular biology and Barrett’s adenocarcinoma. Ann Surg. 2001;233(3):322–337.

159. Wilson, S. Systematic review: the effectiveness of hypnotherapy in the management of irritable bowel syndrome. Aliment Pharmacol Ther. 2006;24(5):769–780.

159a. Wolpin, BM. Adjuvant treatment of colorectal cancer. CA Cancer J Clin. 2007;57(3):168–185.

160. Yang, YX, Lichtenstein, GR. Methotrexate for the maintenance of remission in Crohn’s disease. Gastroenterology. 2001;120(6):1553–1555.

161. Yuan, Y. Peptic ulcer disease today. Nat Clin Pract Gastroenterol Hepatol. 2006;3(2):80–89.