Overview


Gastroenterology Surgery Procedure

            Achalasia Cardia
            Hiatus Hernia
            Intestinal Resection
            Appendicectomy
            Hernia Repair
            Gall Bladder
            Splenectomy
            Piles
            Rectal Prolapse
            ERCP (Endoscopic                             Retrograde Cholangio                           Pancreatography)
            Minimally Invasive                               Gastroenterology Surgery
            Cholecystectomy
            Appendectomy
            Surgery For Hiatus Hernia
            Benign And Malignant                         Diseases Of The Food Pipe                 (Esophagus)
            Diseases Of Stomach                          Including Tests For H. Pylori                For Peptic Ulcer
            Diseases Of Small Bowel                      Including Malabsorption                        Syndrome
            Benign And Malignant                         Disorders Of The Biliary Tract
            Acute And Chronic                             Pancreatic Diseases
            Diseases Of Large Bowel
            Liver Diseases Including                       Tests For Viral Profile In                       Hepatitis And Alcohol Related               Problems

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For patients with mild to moderate pancolitis, first-line therapy involves oral 5-ASA agents. If this therapy is ineffective, oral steroids can be used for active disease, with the usual starting prednisone dose of 40 mg per day. For patients with mild to moderate disease who do not completely respond to or are dependent on oral steroids, immunosuppressives such as 6-mercaptopurine or azathioprine can be used. These purine analogues act by causing chromosome breaks and blunt the proliferation of rapidly dividing cells, such as lymphocytes. These agents are effective for active disease and maintaining remission. Thiopurine methyltransferase (TPMT) activity should be measured before initiating therapy to determine the optimal starting dose. Metabolite levels of 6-MP (6-thioguanine [6-TG] and 6-methylmercaptopurine [6-MMP]) can be measured to determine the optimal therapeutic dose with the minimal risk of toxicity. 6 Measurements of metabolite levels are best done on patients who are not responding, but who are on adequate doses. Metabolite levels can be used to distinguish between those who are nonresponders, those who are not compliant with medication, and those in whom the dose can be safely increased. One shortcoming, however, is that 6-MP and azathioprine usually require 3 to 6 months to become maximally effective. In addition, they have the rare side effects of allergy (e.g., abdominal pain, fever, rash), pancreatitis, and bone marrow suppression.


For ulcerative colitis patients with severe colitis refractory to maximal oral therapy, admission to the hospital and intravenous steroids are required. The usual dosage of intravenous steroids is 0.5 to 0.75 mg/kg/day of prednisone equivalence. Usual regimens include intravenous hydrocortisone 100 mg every 8 hours or intravenous methylprednisolone 40 mg daily. It is important to rule out toxic megacolon by checking a radiograph of the abdomen. A colorectal surgery consultation should be obtained, because a significant number of these patients may require surgery during their hospitalization. Indications for a colectomy during a colitis flare include massive hemorrhage, perforation, toxic megacolon, or active disease unresponsive to conventional therapy. Surgery is also indicated for patients with persistent moderate disease that is medically refractory or for those with intolerable steroid side effects. Cyclosporine has been shown to be useful in the treatment of severely active ulcerative colitis as an alternative to colectomy. 7 However, because cyclosporine has many side effects and has not been shown to be effective in maintaining remission long term, this medication is not widely used in the treatment of severe ulcerative colitis. Infliximab, a monoclonal chimeric anti-TNF antibody, has been approved for use in ulcerative colitis and can induce remission in severely active cases. 8,9 Maintenance therapy with infliximab and an immunosuppressive agent should be considered in patients whose remission was induced with infliximab.


Crohn's Disease

Therapy for Crohn's disease has been discussed in practice guidelines published in 1997. 10 These guidelines set up a definition for the severity of a Crohn's disease flare. Mild to moderate disease is indicated when patients are able to tolerate oral intake without dehydration, high fever, abdominal pain, abdominal mass, or obstruction. Moderate to severe disease describes the disorder in patients who have failed to respond to therapy for mild or moderate disease or those with fevers, weight loss, abdominal pain, anemia, or nausea and vomiting without frank obstruction.


Severe to fulminant disease describes patients with persisting symptoms despite the introduction of steroids on an outpatient basis or those presenting with high fever, persistent vomiting, obstruction, rebound tenderness, cachexia, or an abscess. In addition, it is important to distinguish between differing behaviors of disease—inflammatory, fistulizing, or fibrostenotic.


For Crohn's disease patients with mild to moderate disease, oral mesalamine is only modestly effective and is not approved for use. Whereas sulfasalazine has some potential benefit in the treatment of colonic disease, it is not useful for isolated small bowel disease. Budesonide is a topically active corticosteroid that when given orally, is effective in treating mucosal inflammation and is then inactivated through first-pass metabolism. The side effect profile of budesonide is much better than oral corticosteroids. In patients with mildly to moderately active Crohn's disease, budesonide 9 mg daily was found to be significantly better in inducing remission than 4 g daily of a mesalamine preparation. 11 Gastroduodenal Crohn's disease has been shown to improve with oral proton pump inhibitors.


For moderate to severe Crohn's disease, oral steroids are often necessary. Prednisone is dosed as in ulcerative colitis patients at 40 mg per day. It is important to rule out any concomitant infection or abscess before initiating steroid therapy. For patients who are steroid-resistant or who have become steroid-dependent, 6-MP, azathioprine, or methotrexate can be used. These agents have been shown to be safe and effective in Crohn's disease, enabling patients to avoid long-term use of corticosteroids. Infliximab has been shown to be effective for the acute management of both inflammatory and fistulous Crohn's disease. 12,13 Infliximab also is effective for maintenance therapy of both inflammatory and fistulous Crohn's disease. 14 Infliximab is typical dosed at 5 mg/kg over 2 hours and given every 8 weeks after a loading regimen of three doses over 6 weeks. Adverse side effects include infusion reaction, infections, including tuberculosis and other opportunistic infections, and lymphoma. A skin test (e.g., purified protein derivative or Mantoux test) should be performed before initiating infliximab therapy, even in those who have been vaccinated against tuberculosis with BCG (Bacille Calmette-Guérin). A positive skin test is a contraindication to use of infliximab.


For Crohn's disease patients with severe or fulminant disease, hospitalization is advisable. An abdominal computed tomography (CT) scan should be obtained if an abscess is clinically suspected. Stool studies should be done to rule out infection. Once this has been excluded, intravenous steroids should be instituted in the same doses as those used for ulcerative colitis. Surgical intervention is indicated with perforation, obstruction, or fulminant disease unresponsive to medical therapy.


Outcomes

Colorectal Cancer

Patients with ulcerative colitis or Crohn's disease have an increased risk of colonic epithelial dysplasia and carcinoma. Ulcerative colitis patients have a colon cancer risk at least three times higher than that in the general population. This risk of colon cancer is higher with both increasing duration and extent of disease, as well as with primary sclerosing cholangitis. Crohn's disease patients with at least 30% of the colon involved with disease may have an increased risk of colorectal dysplasia and cancer.


Entering a patient into a cancer surveillance program is important in both these groups. However, the exact method and timing of surveillance are still a matter of much debate. Most guidelines recommend beginning screening colonoscopies after 8 years of disease. Multiple biopsies should be taken at regular intervals throughout the colon; these include polypoid lesions and examination for the premalignant neoplastic lesion of dysplasia. All specimens with any grade of dysplasia should be reviewed by an expert gastrointestinal pathologist to confirm the findings.


It is generally agreed that high-grade dysplasia is an absolute indication for a colectomy, because these patients have a 42% risk for concurrent cancer. 15 Low-grade dysplasia in flat mucosa also is an indication for colectomy, because progression to more advanced neoplasia often occurs. 16


The frequency with which colonoscopic screenings should be performed varies according to the extent of colitis, duration of disease, and history of primary sclerosing cholangitis. Because the risk of cancer is low throughout the first decade after the diagnosis of ulcerative colitis, surveillance need not be performed more frequently than every 3 years. As the cancer risk increases, the testing interval should shorten. One reasonable approach calls for tests every 3 years for 12 years, then every 2 years for 10 years, and annually thereafter. Patients with primary sclerosing cholangitis have an increased risk of colorectal cancer, so endoscopic surveillance examinations should be performed annually.


Ileal Pouch

Ulcerative colitis patients who require surgery are often offered an ileal pouch. At surgery, a total proctocolectomy is done, the distal small bowel is fashioned into a J-shaped reservoir, and the ileal pouch is stapled to the anal verge. Following surgery, patients usually have four to seven bowel movements daily and occasional or minimal incontinence. Acute pouchitis, the most common complication, will occur in about 25% to 50% of patients within 5 years. Acute pouchitis is usually successfully treated with antibiotics such as metronidazole or ciprofloxacin. Other less common complications of the ileal pouch include chronic pouchitis (inadequate response of pouchitis to multiple rounds of antibiotics), irritable pouch syndrome (bowel symptoms without endoscopic inflammation), cuffitis (recrudescence of colitis in the retained rectal cuff), chronic pouchitis, or even unsuspected Crohn's disease. 17 Irritable pouch syndrome often responds to antispasmodics or antidepressants, cuffitis responds to 5-ASA (Canasa) suppositories, chronic pouchitis responds to long-term antibiotics, probiotics, or immunosuppressive therapy, and Crohn's disease of the ileal pouch will require immunosuppressive therapy for treatment.


Summary


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Table : Aminosalicylates and Intestinal Activity
Colon Activity
Medication Dosage (g/day) Distal Proximal Small Bowel Activity
Sulfasalazine 2-8 ++ +++ --
Olsalazine (Dipentum) 1-3 ++ +++ -
Balsalazide (Colazal) 6.75-12 ++ +++ -
Mesalamine (5-aminosali
cylic acid)
Pentasa 2-4 ++ ++ ++
Asacol 2.4-4.8 ++ +++ +
Rowasa enemas 4 +++ - -
Canasa suppositories 2-4 + - -
Small Bowel Disease India offers information on Small Bowel Disease in India, Small Bowel Disease cost India, Small Bowel Disease hospital in India, Delhi, Mumbai, Chennai, Hyderabad & Bangalore, Small Bowel Disease Surgeon in India.

The Division of Gastroenterology provides diagnosis and treatment for small bowel disease, including :

Inflammatory Bowel Disease

The two main categories of inflammatory bowel disease are ulcerative colitis and Crohn's disease. Ulcerative colitis is characterized by recurring episodes of inflammation of the mucosal layer of the large bowel not related to an intestinal infection or nonsteroidal anti-inflammatory drug (NSAID) use. The inflammation involves the rectum and may extend proximally in a continuous fashion. Ulcerative proctosigmoiditis refers to inflammation extending into the sigmoid colon. Left-sided colitis refers to inflammation extending up to, but not beyond, the splenic flexure. Pancolitis refers to disease that extends proximal to the splenic flexure.


Crohn's disease is characterized by recurring episodes of inflammation of any part of the bowel, from the mouth to the anus. This inflammation is transmural, and can result in strictures, microperforations, and fistulae. The inflammation is noncontiguous and thus can produce skip lesions throughout the bowel. Histologically, Crohn's disease can have either transmural lymphoid aggregates or non-necrotizing granulomas. Although granulomas are pathognomonic, they are seen in only 10% of patients with Crohn's disease.


Pathophysiology

The causes of ulcerative colitis and Crohn's disease are not known. However, a reasonable hypothesis for the pathogenesis of inflammatory bowel disease can be presented. As yet unidentified antigens, possibly a mycobacterium, paramyxovirus, or components of cigarette smoke, activate resting macrophages to release a wide variety of cytokines. 3 Cytokines is a collective term for a group of low-molecular-weight peptides that are active at low concentrations and bind to specific receptors to produce autocrine, paracrine, and endocrine effects. The most abundant cytokine is interleukin-1 (IL-1), which not only causes diarrhea but also acts as a pyrogen. Other cytokines activated in the inflammatory process are IL-6, tumor necrosis factor a (TNF-a), and the chemokine IL-8. Cytokines cause differentiation of lymphocytes to different types of T cells. Helper T cells, type 1 (Th-1), are associated principally with Crohn's disease, whereas Th-2 cells are associated principally with ulcerative colitis. These cytokines serve to stimulate the immune system and cause an inflammatory reaction, thus producing tissue damage in the intestinal mucosa.


Signs and symptoms

Ulcerative colitis patients typically present with rectal bleeding, diarrhea, tenesmus (urgent desire to evacuate the bowels but with passage of little stool), and abdominal pain. Patients with fulminant or toxic colitis usually have more than ten bowel movements daily, continuous bleeding, abdominal distention and tenderness, and radiologic evidence of edema and possibly bowel dilation.

Crohn's disease patients typically present with diarrhea, abdominal pain, and weight loss. The abdominal pain usually is insidious, is in the right lower quadrant, occurs soon after eating, and may be associated with a tender inflammatory mass. There may be hematochezia, but bleeding is much less common than in ulcerative colitis patients. Fever, weight loss, stomatitis, perianal fistulae or fissures (or both), arthritis, and erythema nodosum are all commonly seen.

There are many extraintestinal manifestations in inflammatory bowel disease. Approximately 2% of ulcerative colitis patients will develop primary sclerosing cholangitis, a cholestatic liver disease diagnosed by the appearance of extrahepatic and intrahepatic strictures on a cholangiogram. Primary sclerosing cholangitis is seen more often in ulcerative colitis than in Crohn's disease patients. 4 Other hepatic manifestations of inflammatory bowel disease include fatty liver, chronic active hepatitis, amyloidosis, and complications from medications used to treat inflammatory bowel disease (e.g., steroids, azathioprine, 6-mercaptopurine [6-MP], sulfasalazine, infliximab).

Erythema nodosum, seen in up to 3% of patients, is characterized by raised, tender, erythematous nodules appearing typically on the extremities. Pyoderma gangrenosum, a rare, ulcerating, necrotic lesion, is seen in both Crohn's disease and ulcerative colitis. Arthritis usually is seronegative, mono- or pauciarticular, and asymmetrical. The large joints are most often affected, and there is no synovial destruction. Ocular manifestations include blurred vision, eye pain, photophobia, and keratitic precipitates. Patients with uveitis often have human leukocyte antigen B27 (HLA-B27), whereas patients with episcleritis and iritis usually do not. Cerebrovascular accidents and other thromboembolic events can result from hypercoagulability secondary to chronic inflammation or to other inherited syndromes, such as the factor V Leiden mutation. Patients are susceptible to nephrolithiasis from calcium oxalate stones.


Diagnosis

The diagnosis of ulcerative colitis or Crohn's disease is established by finding characteristic intestinal ulcerations and excluding alternative diagnoses, such as enteric infections, ischemia, diverticulitis, or NSAID-induced enteropathy. Active disease in ulcerative colitis is characterized by the endoscopic appearance of superficial ulcerations, friability, a distorted mucosal vascular pattern, and exudates (Fig. 1). Patients with severely active disease can have pseudopolyp formation and deep ulcers and friability that result in spontaneous bleeding. The typical distribution of disease is continuous from the rectum proximally. However, patients with partially treated ulcerative colitis may have discontinuous or patchy involvement.


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The ulcerations of Crohn's disease may appear aphthoid, but could also be deep and serpiginous. Skip areas, a cobblestone appearance, pseudopolyps, and rectal sparing are characteristic findings (Fig. 2). On a small bowel series, Crohn's disease often is manifests by separation of bowel loops and a narrowed terminal ileal lumen, the so-called “string sign”.

Histologic features of ulcerative colitis include disease limited to the mucosa and submucosa, mucin depletion, ulcerations, exudate, and crypt abscesses. In Crohn's disease, non-necrotizing granulomas, transmural lymphoid aggregates, and microscopic skip lesions can be seen. Typical lesions of Crohn's disease also may be seen in the upper gastrointestinal tract. The inflammation is localized in the ileocecal region in 50% of cases, the small bowel in 25%, the colon in 20%, and the upper gastrointestinal tract or perirectum in 5%.

The diagnosis of inflammatory bowel disease can be made only when other reasonable alternatives in the differential diagnosis have been excluded (Box 1). The most common diagnoses that mimic ulcerative colitis are the infectious colitides. It is imperative to check stool for enteric pathogens, including ova and parasites, Escherichia coli O157:H7, and Clostridium difficile. Infection with Yersinia enterocolitica or Mycobacterium tuberculosis can cause inflammation in the terminal ileum resembling Crohn's disease. Other important diseases in the differential diagnosis of Crohn's disease include intestinal lymphoma, celiac sprue, radiation enteropathy, and NSAID-induced enteropathy.


Ulcerative Colitis


Crohn's Disease

Treatment

Ulcerative Colitis

Management of ulcerative colitis is described in practice guidelines published in 2004. 5 The severity of the ulcerative colitis flare is based on patient symptoms and on the extent of colitis, not on the histologic severity of inflammation.

For patients with mild to moderate distal or left-sided colitis, therapy includes oral or topical agents, or both. Mesalamine (5-aminosalicylic acid [5-ASA]) enemas (Rowasa) are frequently used topical agents, and given 4 g daily. They are effective for both active colitis and for maintaining a patient in remission, and are superior to rectal corticosteroids for distal disease. Steroid enemas are effective in active disease, but are not useful in maintaining a remission. Mesalamine suppositories (Canasa) are also useful for patients with proctitis. Mesalamine therapy has not failed until a patient has been given maximal doses of the drug or has experienced intolerable side effects. Asacol, 2.4 g per day, is given for maintenance, up to 4.8 g per day for active disease. Sulfasalazine, 2 g per day, is given for maintenance, and up to 8 g per day for active disease. Pentasa, 2 g per day, is given for maintenance, and up to 4 g per day for active disease ( Table 1 ). The combination of oral and topical mesalamine is more effective than either alone for active disease. Although sulfasalazine is less expensive than the other 5-ASA agents, it has a high frequency of side effects, such as nausea, vomiting, anorexia, dyspepsia, malaise, and headaches. Some rare idiosyncratic reactions include fever, rash, hepatitis, pancreatitis, pneumonitis, and agranulocytosis. Folate supplementation is recommended, because sulfasalazine can inhibit folate absorption. The other 5-ASA agents can be more expensive but generally are better tolerated.



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