Improved Outcomes in Colon and Rectal Surgery part 35 ppsx

 improved outcomes in colon and rectal surgery 12. Carter FM, McLoed, Cohen Z. Subtotal colectomy for ulcer- ative colitis: complications related to the rectal remnant. Dis Colon Rectum 1991; 34: 1005–9. 13. Karch LA, Bauer JJ, Gorfine SR et al. Subtotal colectomy with Hartmann’s pouch for inflammatory bowel disease. Dis Colon Rectum 1995; 38: 635–9. 14. Boushey RP, Marcello PW, Martel G et al. Laparoscopic total colectomy: an evolutionary experience. Dis Colon Rectum 2007; 50: 1512–19. 15. Eaden JA, Abrams K, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 2001; 48: 526–35. 16. Hata K, Watanabe T, Kazama S et al. Earlier surveillance colonoscopy programme improves survival in patients with ulcerative colitis associated colorectal cancer: results of a 23-year surveillance programme in the Japanese population. Br J Cancer 2003; 89: 1232–6. 17. Mpofu C, Watson AJ, Rhodes JM. Strategies for detecting colon cancer and/or dysplasia in patients with inflammatory bowel disease. Cochrane Database Syst Rev 2004; 2: CD000279. 18. Bernstein CN, Shanahan F, Weinstein WM. Are we telling patients the truth about surveillance colonoscopy in ulcer- ative colitis? Lancet 1994; 343: 71–4. 19. Connell WR, Lennard-Jones JE, Williams CB et al. Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis. Gastroenterology 1994; 107: 934–44. 20. Befrits R, Ljung T, Jaramillo E et al. Low-grade dysplasia in extensive, long-standing inflammatory bowel disease: a fol- low-up study. Dis Colon Rectum 2002; 45: 615–20. 21. Gumaste V, Sachar DB, Greenstein AJ. Benign and malignant strictures in ulcerative colitis. Gut 1992; 33: 938–41. 22. Camilleri-Brennan J, Munro A, Steele FJ. Does an ileostomy pouch offer a better quality of life than a permanent ileos- tomy for patients with ulcerative colitis. J Gastrointest Surg 2003; 7: 814–9. 23. Carlsen E, Bergan A. Technical aspects and complications of end ileostomies. World J Surg 1995; 19: 632–5. 24. Berry AR, Campos RDE, Lee ECG. Perineal and pelvic mor- bidity following perimuscular excision of the rectum for inflammatory bowel disease. Br J Surg 1986; 73: 675–7. 25. Rivadeneira DE, Schoetz DJ, Marcello PW et al. Vacuum- assisted closure of complex wounds of the perineum; a new paradigm in perineal wound care (abstract). Dis Colon Rectum 2003; 46: A67. 26. Dozois E. Proctocolectomy and Brooke ileostomy for chronic ulcerative colitis. Clin Colon Rectal Surg 2004; 17: 65–70. 27. Wickland M, Jansson I, Asztely M et al. Gynaecological problems related to anatomical changes after conventional proctocolectomy and ileostomy. Int J Colorect Dis 1990; 5: 49–52. 28. Camillari-Brennan J, Steele RJ. Objective assessment of qual- ity of life following panproctocolectomy and ileostomy for ulcerative colitis. Ann R Coll Surg 2001; 83(5): 321–4. 29. Pemberton JH, Phillips SF, Ready RR et al. Quality of life after Brooke ileostomy and ileal pouch-anal anastomosis for chronic ulcerataive colitis. Comparison of performance sta- tus. Ann Surg 1989; 209: 620–8. 30. Kock NG. Intra-abdominal “reservoir” in patients with per- manent ileostomy. Preliminary observations on a procedure resulting in fecal “continence” in five ileostomy patients. Arch Surg 1969; 99: 223–31. 31. Nessar G, Fazio VW, Tekkis P et al. Long-term outcome and quality of life after continent ileostomy. Dis Colon Rectum 2006; 49: 336–44. 32. Castillo E, Thomassie LM, Whitlow CB et al. Continent ileostomy: current experience. Dis Colon Rectum 2005; 48: 1263–8. 33. Beck DE. Clinical aspects of continent ileostomy. Clinics in colon and rectal surgery 2004; 17: 57–63. 34. Kaiser AM, Stein JP, Beart RW Jr. T-pouch: a new valve design for a continent ileostomy. Dis Colon Rectum 2002; 45: 411–5. 35. Fazio VS, Church JM. Complications and function of the continent ileostomy at the Cleveland Clinic. World J Surg 1988; 12: 148–54. 36. Lepisto AH, Jarvinen HJ. Durability of Kock continent ileos- tomy. Dis Colon Rectum 2003; 46: 925–8. 37. Pastore RLO, Wolff BG, Hodge D. Total abdominal colectomy and ileorectal anastomosis for inflammatory bowel disease. Dis Colon rectum 1997; 40: 1455–64. 38. Elton C, Makin G, Hitos K et al. Mortality, morbidity and functional outcome after ileorectal anastomosis. Br J Surg 2003; 90: 59–65. 39. Khubchandani IT, Sandfort MR, Rosen L et al. Current sta- tus of ileorectal anastomosis for inflammatory bowel disease. Dis Colon rectum 1989; 32: 400–3. 40. Lofberg R, Leijonmarck CE, Bronstrom O. Mucosal dysplasia and DNA content in ulcerative colitis patients with ileorectal anastomosis. Follow-up study in a definite patient group. Dis Colon Rectum 1991; 34: 566–71. 41. Gruner OP, FLatmark A, Naas R et al. Ileorectal anasto- mosis in ulcerative colitis. Results in 57 patients. Scand J Gastroenterol 1975; 10: 641–6. 42. Paoluzi OA, Dipaolo MC, Ricci F et al. Ileo-rectal anasto- mosis in ulcerative colitis: results of a long-term follow-up study. Ital J Gastroenertol 1994; 26: 392–7. 43. Marcello PW, Milsom JW, Wong SK et al. Laparoscopic restorative proctocolectomy: case-matched comparative study with open restorative proctocolectomy. Dis Colon Rectum 2000; 43: 604–8. 44. Tilney HS, Lovegrove RE, Heriot AG et al. Comparison of short-term outcomes of laparoscopic vs. open approaches to ileal pouch surgery. Int J Colorectal Dis 2007; 22: 531–42. 45. Larson DW, Davies MA, Dozois EJ et al. Sexual function, body image and quality of life after laparoscopic and open ileal pouch-anal anastomosis. Dis Colon Rectum 2007; 51: 392–6. 46. Browning SM, Nivatvongs S. Intraoperative abandonment of ileal pouch to anal anastomosis-the Mayo Clinic experience. J Am Coll Surg 1998; 186: 441–6. 47. Smith L, Friend WG, Medwell SJ. The superior mesenteric artery. The critical factor in the pouch pull-through proce- dure. Dis Colon Rectum 1984; 27: 741–4.  surgery for ulcerative colitis 48. Burnstein MJ, Schoetz DJ, Coller JA, Veidenheimer MC. Technique of mesenteric lengthening in ileal reservoir-anal anastomosis. Dis Colon Rectum 1987; 30: 863–6. 49. Metcalf DR, Nivatvongs S, Sullivan TM et al. A technique of extending small-bowel mesentery for ileal pouch-anal anasto- mosis: report of a case. Dis Colon Rectum 2008; 51(3): 363–4. 50. Hueting WE, Buskens E, Tweel IVD et al. Results and compli- cations after ileal pouch anal anastomosis: a meta-analysis of 43 observational studies comprising 9,317 patients. Dig Surg 2005; 22: 69–79. 51. Bullard KM, Madoff RD, Gemlo BT. Is ileoanal pouch func- tion stable with time/ Results of a prospective audit. Dis Colon Rectum 2002; 45(3): 299–304. 52. Cornish JA, tan E, Teare J, Teoh TG et al. The effect of restor- ative proctocolectomy on sexual function, urinary function, fertility, pregnancy and delivery: a systematic review. Dis Colon Rectum 2007; 50: 1128–38. 53. Counihan TC, Roberts PL, Schoetz DJ et al. Fertility and sex- ual and gynecological function after ileal pouch anal anasto- mosis. Dis Colon Rectum 1994; 37: 1126–9. 54. Marcello PW, Roberts PL. Cystic pelvic masses. Seminars in colon and rectal surgery 1997; 8; 190–7. 55. Francois Y, Dozois RR, Kelly KA et al. Small intestinal obstruction complicating ileal-pouch-anal anastomotis. Ann Surg 1989; 209: 46–50. 56. Marcello PW, Roberts PL, Schoetz JD Jr et al. Obstruction after ileal pouch-anal anastomosis: a preventable complica- tion? Dis Colon Rectum 1994; 37: 1176–7. 57. MacLean AR, Cohen Z, MacRae HM et al. Risk of small bowel obstruction after the ileal pouch-anal anastomosis. Ann Surg 2002; 235: 200–6. 58. Becker JM, Dayton MT, Fazio VW et al. Prevention of postop- erative abdominal adhesions by a sodium hyaluronate-based bioresorbable membrane: a prospective, randomized, double- blind multicenter study. J Am Coll Surg 1996; 183: 297–306. 59. Fazio VW, Ziv Y, Church JM et al. Ileal pouch-anal anasto- moses complications and function in 1005 patients. Ann Surg 1995; 222: 120–7. 60. Scott NA, Dozois RR, Beart RW et al. Postoperative intra- abdominal and pelvic sepsis complicating ileal pouch anal anastomosis. Int J Colorectal Dis 1988; 3: 149–52. 61. Weston-Petrides GK, Lovegrove RE, Tilney HS et al. Comparison of outcomes after restorative proctocolectomy with or without defunctioning ileostomy. Arch Surg 2008; 143(4): 406–12. 62. Ziv Y, Fazio VW, Church JM et al. Stapled ileal pouch-anal anastomoses are safer than handsewn anastomosis in patients with ulcerative colitis. Am J Surg 1996; 171: 320–3. 63. Gorgun E, Remzi FH. Complications of ileoanal pouches. Clin Colon Rectal Surg 2004; 17: 43–55. 64. Raval MJ, Schnitzler M, O’Connor BI et al. Improved out- come due to increased experience and individualized man- agement of leaks after ileal pouch-anal anastomosis. Ann Surg 2007; 246: 763–70. 65. Prudhome M, Dozois RR, Godlewski G et al. Anal can- cal strictures after ileal pouch-anal anastomosis. Dis Colon Rectum 2003; 46: 20–3. 66. Marcello PW, Roberts PL, Schoetz DJ Jr et al. Long-term results of the ileoanal pouch procedure. Arch Surg 1993; 128: 500–4. 67. Fazio VW, Tjandra JJ. Pouch advancement and neoileoa- nal anastomosis for anastomotic stricture and anovaginal fistula complicating restorative proctocolectomy. Br J Surg 1992; 79: 694–6. 68. Fleshner PR, Schoetz DJ Jr. Surgical management of ulcer- ative colitis in the ASCRS textbook of colon and rectal sur- gery, 2007: 567–83. 69. Fazio VW, Ziv Y, Church JW et al. Ileal pouch-anal anas- tomosis complications and function in 1005 patients. Ann Surg 1995; 222: 120–7. 70. Shah NS, Remzi FH, Massman A et al. Management and treat- ment outcome of pouch-vaginal fistulas following restorative proctocolectomy. Dis Colon Rectum 2000; 46: 911–7. 71. Lohmuller JL, Pemberton JH, Dozois R et al. Pouchitis and extraintestinal manifestations of inflammatory bowel dis- ease after ileal pouch-anal anastomosis. Ann Surg 1990; 211: 622–7. 72. Penna C, Dozois R, Tremaine W et al. Pouchitis after ileal pouch-anal anastomosis for ulcerative colitis occurs with increased frequency in patients with associated primary scle- rosing cholangitis. Gut 1996; 38: 234–9. 73. Sanborn WJ, Tremaine WJ, Batts KP et al. Pouchitis after ileal pouch-anal anastomosis: a pouchitis disease activity index. Mayo Clin Proc 1994; 69: 409–15. 74. Fazio VW, Wu JS, Lavery IC. Repeat ileal pouch-anal anas- tomosis to salvage septic complications of pelvic pouches: clinical outcome and quality of life assessment. Ann Surg 1998; 228: 588–97. 75. Lovegrove RE, Herior AG, Constantinides V et al. Meta- analysis of short-term and long-term outcomes of J, W, and S ileal reservoirs for restorative proctocolectomy. Colorectal Dis 2006; 9: 310–20. 76. Seow-Choen F, Tsunoda A, Nicholls RJ. Prospective randomized trial comparing anal function after hand-sewn ileoanal anasto- mosis vs. stapled ileoanal anastomosis without mucosectomy in restorative proctocolectomy. Br J Surg 1991; 78: 430–4. 77. Luukkonen P, Jarvinen H. Stapled vs. hand sutured ileoanal anastomosis in restorative proctocolectomy: a prospective randomized trial. Arch Surg 1993; 128: 437–40. 78. Reilly WT, Pemberton JH, Wolff BG et al. Randomized prospective trial comparing ileal pouch-anal anastomosis performed by excising the anal mucosa to ileal pouch-anal anastomosis. Ann Surg 1997; 225: 666–76. 79. Lovegrove RE, Constantinides VA, Heriot AG et al. A com- parison of hand-sewn vs. stapled ileal pouch anal anasto- mosis (IPAA) following proctocolectomy-a meta-analysis of 4183 patients. Ann Surg 2006; 244: 18–26. 80. O’Riordain MG, Fazio VW, Lavery IC et al. Incidence and natural history of dysplasia of the anal transitional zone after ileal pouch-anal anastomosis: results of a five-year to ten- year follow-up. Dis Colon Rectum 2000; 43: 1660–5. 81. Herline AJ, Meisinger LL, Rusin LC et al. Is routine pouch surveillance for dysplasia indicated for ileoanal pouches? Dis Colon Rectum 2003; 46: 156–9.  improved outcomes in colon and rectal surgery 82. Hyman NH, Fazio VW, Tuckson WB, Lavery IC. Consequences of ileal pouch-anal anastomosis for Crohn’s colitis. Dis Colon Rectum 1991; 34: 653–7. 83. Sagar PM, Dozois RR, Wolff BG. Long-term results of ileal pouch-anal anastomosis in patients with Crohn’s disease. Dis Colon Rectum 1996; 39: 893–8. 84. Keighley MR. The final diagnosis in pouch patients for presumed ulcerative colitis may change to Crohn’s disease; patients should be warned of the consequence. Acta Chir Iugosl 2000; 47: 27–31. 85. Braveman JM, Schoetz DJ, Marcello PW et al. The fate of the ileal pouch in patients developing Crohn’s disease. Dis Colon Rectum 2004; 47: 1613–20. 86. Melmed GY, Fleshner PR, Bardakcioglu O et al. Family history and serology predict Crohn’s disease after ileal-pouch-anal anas- tomosis for ulcerative colitis. Dis Colon Rectum 2008; 51: 100–8.  2 Surgery for Crohn’s disease Jorge Canedo, Tolga Erim, and Steven D Wexner INTRODUCTION Crohn’s Disease (CD) is a lifelong disorder of unknown etiology characterized by chronic focal, transmural, and granulomatosos inflammation that can affect any portion of the gastrointesti- nal tract. The transmural inflammation often leads to fibrosis and to obstructive clinical presentations. Crohn’s disease was first described by B. Crohn, L.Ginzburg, and G.Oppenheimer in 1932 as an inflammatory condition limited to the terminal ileum.(1) Later, Lockhart-Mummery and Morson (2) described granulomatous colitis, and the disease process was understood to potentially affect the large bowel. It can occur from the mouth through the anus. The clinical symptoms are related to the site of the disease. As it is more prevalent among the terminal ileum and right colon, the most frequently symptoms are: diarrhea, weight loss, abdominal pain, and perineal disease. But the clinical features indicate the site of the disease.(3) a) Oral: Aphthous ulceration on the background of a mucosal edema is the most common oral manifestation of CD. Additional lesions described include: granulomatous masses, chelitis, and granulomatous sialadenitis. Lesions usually coex- ist with an intestinal disease. b) Esophagus: Although more rare, lesions here may cause dysphagia or pain. c) Stomach and duodenum: Less than 5% of the patients pres- ent with gastroduodenal Crohn’s disease; the distal antrum and the duodenum are the most commonly affected areas. Both sites can present as a peptic ulcer disease. In addition, outlet gastric obstruction may occur after a healing stricture in the antrum. d) Small bowel: Some findings of extended involvement include malabsorption, protein-losing enteropathy, diarrhea, anemia, and steatorrhea. If segmental thickening or structuring devel- ops, the patient may present with obstructive symptoms. e) Ileocecal: Symptoms of obstruction are more frequently due to inflammatory swelling or structuring. Transmural inflam- mation and local sepsis often result in a palpable inflamma- tory mass in the right lower quadrant. f) Colon: involvement often includes the symptoms of diar- rhea, associated with pain. g) Perianal disease: Is common and may precede other manifesta- tions; as a fistula, an abscess, or one or more fissures and tags. Patients may also have systemic symptoms; fatigue, weight loss, and fever are the primary systemic symptoms in Crohn’s disease. Postprandial obstructed symptoms from narrowed intestinal segments make the patient avoid eating. Weight loss may also be related to malabsorption and, in children, may be the presenting sign before any obvious intestinal manifestations of the disease. Fever is common in patients with Crohn’s disease and may be due to other chronic inflammation or due to a perforation with associated fistula or abscess. Crohn’s disease is diagnosed most frequently among people aged 15 to 30 years, with no differences in prevalence between males and females. However, there is a second peak between the sixth and seventh decades of life (4) and diagnosis may also be made during early childhood. Since its discovery in the Mount Sinai Hospital in New York City almost 76 years ago, the exact cause of Crohn’s disease remains unknown. Among many theories are genetic, immunologic, bacterial, and bacterial antigens. The current theory about the pathophysiology is that the intestinal flora, in conjunction with unidentified environmental factors trigger and drives an exaggera- dated immunologic response in a genetically susceptible host.(5) The result is a chronic inflammation that typically extends beyond the mucosa and throughout to the serosa. Potential risk factors to develop CD are smoking and having first degree relatives with the disease.(6) EVALUATION Symptoms of CD are heterogeneous, but most of the time include diarrhea for more than 6 weeks, abdominal pain, and weight loss. In most cases, the patient will have a clinic, radiologic, endoscopic, and histological evaluation to have its diagnosis. Crohn’s disease most often involves the distal small bowel and proximal large bowel. Almost one half of all patients have dis- ease that involves both the ileum and the colon. While another one-third have disease confined to the small bowel, primarily the terminal ileum. The clinical presentation might be divided according to the main symptoms into: 1. Intestinal Symptoms 2. Extraintestinal symptoms 3. Biliary and Liver Manifestations The patient with CD should undergo complete evaluation. In most cases, the leading symptom that precipitates evaluation is diarrhea. Eighty-five percent of patients with CD report more than 5 bowel movements (BM) per day and weight loss as part of the initial diagnosis.(7) The history and physical examina- tion might uncover general complaints including weakness and fatigue. In addition, as mentioned above, there are the specific symptoms according to disease site. On physical examination, paleness of the mucosa could indicate anemia. Iron deficiency anemia occurs in up to 30% of the patients. (8) Typically, the abdominal examination reveals abnormal bowel sounds, detection of an abdominal mass, and pain to palpation. Inspection of the perianal regional can provide evidence of fistula, fissure, abscess, or skin tap. Rectal digital examination might detect a stenosis or blood. 2 improved outcomes in colon and rectal surgery The initial complementary evaluation starts with blood tests and stool examination. Blood tests Blood tests can either provide specific or nonspecific diagnosis, as well the general health status of the patient. The introduction of biological therapies in IBD has renewed interest in inflamma- tory markers (especially C reactive protein (CRP)), given their potential to select responders to these treatments. Controversy exists as to whether or not CRP is a useful marker, and should be preferred in CD as it correlates well with disease activity.(9) But a more recent study showed that neither CRP nor other biological markers were associated with the endoscopic lesions. (10) Elevated leukocytes and thrombocyte time can also indicate active inflammation. Serologic response to various microbes and autoantigens can develop into CD. In addition to the well-established atypi- cal perinuclear antineutrophil cytoplasmic antibodies (atypical P-ANCA) and anti-Saccharomyces cerevisiae mannan antibodies (ASCA), a number of new antibodies have recently been dis- covered and data on their clinical significance has been rapidly increasing. The combination of atypical P-ANCA and ASCA, may be of help in patients in whom distinction between CD and Ulcerative Colitis is not obvious with the classic diagnostic tools (patient history, radiologic examination, endoscopy and biopsy). Papp et.al (11) analyzed several studies, and found that these combinations had sensitivities of 30% to 64%, specificity more than 90%, and PPV from 77% to 96%. Newer markers derived from various microbial inhabitants of the gut, such as Omp, I2, and CBir1 offer new ways to stratify patients into serologic subgroups. Also, glycan markers including antilaminaribioside carbohydrate antibody (ALCA) (18–38%), antichitobioside car- bohydrate antibody (ACCA) (21–36%), and antimannobioside carbohydrate antibody (AMCA) (28%) may play an important role in making a CD diagnosis or prognosis.(12) More impor- tantly, 24–44% of the CD patients found ASCA negative in one study were positive for one or more of the antiglycan anti- bodies. The combination of several serological markers, such as gASCA, pANCA, and ALCA, had the best accuracy. Their increased amounts and levels of antibody responses against gASCA, ALCA, ACCA, AMCA and Omp were associated with more complicated disease behaviour (44.7% vs. 53.6% vs. 71.1% vs. 82.0%) and a higher frequency of Crohn’s disease-related abdominal surgery (38.5% vs. 48.8% vs. 60.7% vs. 75.4%).(12) Although the prevalence of antibodies is also higher in healthy relatives of IBD patients than in the control population, their role as subclinical markers is yet to be established. Stool marker One example of a stool marker is neutrophil determination. However, neutrophil determination in the stool is inefficient because of its brief lifetime. This means that the sample should be examined within a few hours of its collection. Other exam- ples of stool markers include calprotectin and lactoferrin. They are produced in significant amounts in white blood cells. The mucosal barrier is altered in CD, allowing white cells to cross the intestinal wall. Activated leukocytes infiltrate the mucosa and can be detected in feces. Lactoferrin is an iron-binding glycoprotein found concentrated in the secondary granules of the neutrophils. Granule proteins can be released from living cells, while cell death does not appear to increase this phenom- enon. Calprotectin is a cytoplasmic antimicrobial component in granulocytes, monocytes, and macrophages. But besides its promises, D’Incà et al. (13) observed that calprotectin and lac- toferrin determination appears to reflect endoscopic and his- tological disease activity in ulcerative colitis but not in Crohn’s disease. Images In clinical practice, imaging techniques are used at initial presenta- tion to establish a diagnosis and to assess exact location, extent, and severity of disease at the time. These methods are also used as follow-up during and after treatment to direct treatment strategies and determine optimal choice and dose of medication. Patients with established CD typically undergo many investigations over a lifetime. Small bowel series The small bowel has been defined for many years as the “black box” of the gastrointestinal system, due to its lack of endoscopic acces- sibility. Therefore, the conventional radiological methods (small bowel enteroclysis (SBE) (Figure 32.1a, Figure 32.1b, Figure 32.1c) and small bowel follow through (SBFT)) were the only imaging methods that could provide information on the morphological features of the small bowel valuable in the diagnosis and manage- ment of CD. Both SBE and SBFT, when performed by experienced examiners, appear to be characterized by similar sensitivity (85– 95%) and specificity (89–94%) in detecting the radiological lesions typical of Crohn’s disease.(14) Preference for one technique or the other largely depends on institutional standards. Both procedures are able to evaluate small bowel peristalsis, including the presence of strictures and/or dilations, the distensibility of the intestinal loops, the presence of fistulae, the morphology of circular folds, and morphology of the mucosal surface. Enema For primary evaluation, endoscopy has widely replaced the bar- ium enema (BE) as diagnostic method. However, BE can provide important additional information in the differential diagnosis of chronic inflammatory colonic diseases or if intestinal intubation is not achieved at colonoscopy. The advantage of a BE over endos- copy is a clear and reproducible demonstration of the patterns of distribution and character of the disease as well as the detection of fistulae.(15) With the advance of CT and MRI images, and wireless endoscopic capsule, barium examinations not only of the stomach but also of the colon are decreasing in frequency. The disadvantage of the enema is the same as the one for SBE: limited information about transmural and extraintestinal abnormalities. Upper endoscopy Lemberg et al. (16) concluded the need to include EGD in the evaluation of children suspected of having IBD. The current study  surgery for crohn's disease found that in children with CD, 57.4% had endoscopic abnormal- ities. These findings ranged from mild changes, such as erythema or nodularity of the stomach, to more obvious features, such as ulceration throughout the upper tract and cobblestoning of the duodenum. In total, 80.3% of patients had histologic evidence of inflammation in the upper gut; including granulomata, which were evident in the upper gastrointestinal tract in approximately one-quarter of patients with CD. EGD may help in the differen- tial diagnosis in patients with indeterminate colitis after a biopsy in the normal gastric mucosa (17) and may be used as therapeutic intervention specifically in case of antrual or duodenual stricture. EGD provides good relief in symptomatic patients (17). Figure 32.1 (A) Note the string like narrowing stricture at the terminal ileum (arrows) with proximal bowel obstruction. (X-ray courtesy of Department of radiology Cleveland Clinic Florida) (B-C) Multiple small bowel strictures with associated proximal obstruction. (X-ray courtesy of Department of radiology Cleveland Clinic Florida) (A) (B) (C)  improved outcomes in colon and rectal surgery Colonoscopy Approximately 50 percent of patients have ileocolitis which refers to involvement of both the ileum and colon, highlighting the fact that colonoscopy with intubation of the ileum plays a fundamen- tal role in the diagnosis and evaluation of a patient with Crohn’s Disease. Colonoscopic findings often include segments of normal bowel interrupted by large areas of obvious disease. In CD, the severity of an attack is usually evaluated accord- ing to clinicobiological variables, like the Crohn’s Disease Activity Index. Colonoscopy has an increased risk of complication in such cases. But Nahon et al. (18) demonstrated that colonoscopy in severe colonic CD is useful for the diagnosis of CD versus UC. The benefits increase if the patient is suffering from a first attack of inflammatory bowel disease, a situation which is particularly common in cases of severe colitis, as has been reported in 2.3– 6% of CD.(19) In this study, colonoscopy with biopsies was able to diagnose CD after initial presentation in 50% of patients by showing either involvement of the ileum or intervening zones of healthy mucosa within the colon. According to Minderhound et al. (20), colonoscopy remains the gold standard for assessment of severity of mucosa inflammation compared to several score indexes, as well as serum and fecal markers. Transabdominal ultrasound (US) Parente et al. reviewed several studies that compared the accuracy of bowel US with other imaging techniques (barium X-ray and/ or endoscopy) and surgery in localizing CD lesions within the bowel.(21) But many of these studies have included small num- bers of patients with CD diseases mainly confined to the small bowel. The overall sensitivity for diagnosis disease in the terminal ileum is approximately 90% with specificity of 93–97%. Bowel US has also been used to detect complications of CD. Although the presence of abscesses, fistulae, and strictures may be suspected from clinical history or specific complaints, it is usually necessary to undertake endoscopy, barium studies and computed tomography (CT) to clearly diagnose these complications. Barium studies and CT scans are still considered the methods of choice in detecting internal fistulae and abscesses in CD. Parente et al. in a previous prospective study compared the sensitivity and specificity of bowel US in detecting strictures in small bowel.(22) Computed tomography is currently considered the nonsurgical ‘gold standard’ for the diagnosis of CD-related abscesses. Both CT and barium studies are known for their accuracy in detecting fistu- las, although Maconi et al. (23) demonstrated that CT or SBE alone might miss up to 30% of the fistulas, but US alone or in combina- tion with SBE can detect almost 90% of internal fistulas. US when compared to CT, showed an overall high accuracy comparable in the detection of intraabdominal abscesses. Although CT showed a slightly greater accuracy and positive predictive value than did US. US also has a lower sensitivity in detecting deep abscesses. This finding can be explained by the well-known difficulties associated with transcutaneous US examination of anatomic structures deep in the pelvis or between the intestinal loops, especially when over- lying bowel gas obscures the region of interest. The differentiation between abscess and enlarged loop can be challenging. Another feature in US is its utility in the evaluation of peria- nal disease. Transperineal US is a simple, noninvasive and cheap technique that can be usefully employed to study the pelvis and perianal inflammatory diseases in static and dynamic evaluations. Additional advantages of US are that it does not require costly or specific diagnostic instruments and can be performed with ade- quate training and experience in most hospitals or offices.(24) Doppler sonography is part of the entire sonographic evalua- tion of intestinal diseases which is helpful in estimating disease activity, although it is not acceptable as the sole method to achieve diagnosis.(25) CT scan Conventional. Computed Tomography (CT) has usually been uti- lized for the detection of extraintestinal complications of Crohn’s disease (mainly intraabdominal abscesses) but is also suitable in the evaluation of bowel wall thickness/ strictures, prestenotic dilatations and fistulas. Nonenhanced CT scan is also used in the diagnosis of postoperative complications indicating (intraperitoneal abscesses, anastomotic deiscence, extraabdominal abscesses and fistulas, inci- sional hernias, ascites, volvulus, etc.). Conventional CT is limited in its assessment of the small bowel because of the artifact caused by collapsed bowel loops.(26) Enteroclysis. Because of the problems described above, CT- enteroclysis has been great results. The ability of multislice CT machines to image larger volumes shown (1500 to 2000 mL or more of contrast agent delivered by the positioning of a nasojeju- nal tube) at a faster speed with the ability to perform reconstruc- tion after the examination, has made CTE a more feasible exten- sion of the conventional barium enteroclysis and CT methods of examining the small intestine (Figure 32.2). It can detect active Figure 32.2 New CT scan technology has improved and may substitute for standard SBS in the near future. Note the thickened bowel wall at the stricture (solid arrows) and dilated obstructed proximal bowel (arrows with dashed lines). Image courtesy of Toshiba America Medical systems, Inc.  surgery for crohn's disease inflammatory changes (neutral enteral contrast with intravenous contrast media) and complications such as fistulae, sinus tracts, and strictures (positive enteral contrast).(27) Volumetric. More recently, a row multidetector-computed tomography (MDCT) has been used to perform a virtual colonos- copy. Virtual colonoscopy studies were performed with single- row helical CT scanners using slices of 4 mm thickness.(28) With the advent of MDCT technology, thinner collimation (up to 0.6 mm) is possible. It is possible now to detect flat or ulcerated lesions of the colon, the findings of which in the evaluation of IBD correlated highly with conventional colonoscopic findings.(29) The disadvantages in both CT enteroclysis and volumetric evaluation included: radiation exposure, and the need for intravenous Endoscopic Ultrasound(EUS) In the setting of IBD, EUS has been limited to detecting perianal dis- ease. The accrual of EUS, MRI, and EUA are comparable. At 85%, 87%, and 91% respectively improved upon by employing any two methods.(30) The use in fistula disease is well described; Schwartz et al. (31) showed that EUS may identify patients with fistulae who can discontinue infliximab without the recurrence of a fistula. MRI MRI allows the accurate assessment of both inflammatory changes of the bowel wall and extramural complications of Crohn’s dis- ease. The noninvasiveness of this technique and its lack of ion- izing radiation has prompted many groups to perform systematic studies of MRI for evaluation of Crohn’s disease. Technological advances in MRI, including the use of respiration-suspended sequences, improved coils, fat suppression, and intravenous gado- linium, have extended the use of MRI in the evaluation of the gas- trointestinal tract. MRI is capable of demonstrating pathology in both luminal and perianal Crohn’s disease. One advantage of MRI over other modalities is its ability to differentiate active inflamma- tion from fibrosis in a thickened bowel segment.(32) It is also safe in pregnancy and in renal failure. Inflammatory diseases featuring intestinal wall abnormalities, exoenteric disease manifestations and complications, disease activity, and, to a lesser extent, mucosal abnormalities, can be appreciated on MRI. In addition, it has been reported that the sensitivity and specificity of MRI in assessing disease activity are 92 and 75%, respectively.(33) Despite closure of draining external orifices after infliximab therapy, fistula tracks persist in some patients with varying degrees of residual inflammation, which may cause recurrent fistulas and pelvic abscesses. MRI can detect whether complete fistula fibrosis occurs with complete resolution of inflammation in the internal fistula tracks.(34) Diasadvantages of the MRI include the high cost of the exam and the length of time to perform it. Double Balloon Enteroscopy(DBE) Endoscopic examination of the entire small bowel is technically very difficult. Push endoscopy is often possible only to the proxi- mal jejunum. In 2001, Yamamoto and Kito developed the double balloon method as an insertion technique for the diagnosis and treatment of small bowel disorders.(35) DBE requires bowel prepa- ration, sedation, radiological exposure, and a 60–100 min exami- nation time, but is able to take biopsies and perform therapeutic endoscopy such as endoscopic enteroclysis, hemostasis, and bal- loon dilatation. Oshitani et al. reported their initial experience in 40 patients. Deep small bowel involvement proximal to the terminal ileum was revealed in 27 patients, and 24 (88.9%) of these patients had no involvement of the terminal ileum itself.(36) Another study showed an 80% success rate of stricture dilatation.(37) This tech- nique therefore represents a promising method for diagnosis and therapeutic intervention of small bowel strictures in CD and may be able to avoid surgery in such patients. However, DBE requires an experienced and skilled therapeutic endoscopist and can be quite confusing, and therefore costly. Wireless Endoscopic Capsule Wireless capsule endoscopy (WCE), initially developed for small bowel investigations in patients with occult bleeding, has been studied in small bowel Crohn’s disease. WCE enables a painless and radiation-free examination of much of the small bowel in an unse- dated patient. Based on cost-effectiveness (US$ 20,000.00–US$ 30,000.00), funding issues, and the inability to obtain tissue sam- ples, it is unlikely that WCE will soon become the primary imaging modality used to initiate a diagnosis of Crohn’s disease or to define its extent at relapse.(38) WCE is well-tolerated by most patients, requires no sedation, and carries few side effects. One of the com- plications of WCE is capsule retention. In a series of 52 patients, Park et al. (39) reported 5 retain WEC (9.6%). Two patients (3.8%) had to undergo a surgery for WEC removal. With the development of the “Given Patency Capsule (Given Imaging Ltd, Yoqneam, Israel), capsule technology might be suit- able for cases of suspected intestinal strictures by SBE. This self- dissolving capsule is the same size as a capsule endoscope. The difference is found at the cellophane-walled cylinder filled with lactose, protected by a plug with a specially-sized hole that allows influx of intestinal fluid, which in turn dissolves the lactose in a predetermined amount of time. If the capsule is retained in the gastrointestinal tract, it disintegrates into small, mostly soft, frag- ments which can easily pass through strictures. Spada et al. pro- pective studied 27 patients with known or suspected intestinal stricture. Twenty and two had CD. Twenty-five patients (92.6%) retrieved the “Given Patency Capsule” in the stools, including six of them which were dissolved. In 2 cases (7.4%), the Given Patency Capsule could not be retrieved in stools and expulsion was con- firmed by fluoroscopy and by a Patency Scanner. One case (4.3%) required hospitalization due to intestinal occlusion. But in this case, the Given Patency capsule was retrieved. The authors con- cluded that WEC done with the Given Patency Capsule was a safe procedure even in the presence of stricture disease.(40) PET scan Positron emission tomography with fluorine 18–labeled fluoro- 2-deoxy-D-glucose (FDG-PET) is a functional imaging method used to detect abnormalities in glucose metabolism in a variety of disorders. Neurath et al (41) studied the efficacy of PET scan in detecting active chronic inflammation on inflamed small and large bowel segments in CD, and compared the results to those  improved outcomes in colon and rectal surgery obtained by hydro-MRI and immunoscintigraphy with granulo- cyte antibodies (GABs). The sensitivity was 85%, 87%, and 71%. The specificity was 89%, 93%, and 100%, respectively. FDG-PET appears to be a reliable tool for detecting inflamed gut segments in CD with higher sensitivity and specificity than either MRI or scintigraphy. Scintigraphy An increased number of T cells and macrophages within the gut lumen is a feature of CD. One of the main problems in the clini- cal management of CD is the identification of patients undergoing early relapse in order to ensure that appropriate preventive treat- ment is administered. Follow-up of patients in clinical remission is currently based on the calculations of clinical activity indexes, together with radiological and endoscopic studies. Scintigraphy with 99mTc-labelled interleukin-2 (99mTc-IL2) and with 99mTc- HMPAO-labeled granulocytes (99mTc-WBC) has been evalu- ated to detect the presence and extent of bowel inflammation in patients with long-term inactive CD (>12 months). Annovazzi et al compared the extent of uptake of 99mTc-IL2 and 99mTc-WBC in patients with clinically inactive CD and, despite the absence of symptoms, 62% had either 99mTc-IL2 or 99mTc-WBC posi- tive for inflammation.(42) Scintigraphy with labelled white blood cells (WBC) has been successfully used in CD patients to detect abscesses and to assess disease extent (particularly for the small bowel) and activity. Almer et al compared the 99mTc-WBC to intraoperative and laparotomy findings and found a sensitivity of 85% and specificity of 81% for bowel inflammation.(43) Although not used, scintigraphy can be an option as a noninvasive evaluation for young children and fragile adults who might have more diffi- culty with invasive imaging modalities. Table 32.1 summarizes the efficacy of the exams discussed above.(41, 44, 45) Medical therapy The etiology of Crohn’s disease (CD) is unknown, and therefore no curative treatments are available. The last few years have wit- nessed a significant change in its treatment. Recent debate on medical management of CD has focused on a step-up versus a step-down therapy. Step-up therapy has been the traditional treatment option where steroids and aminosalicylates are started first, and biologics and immunomodulators are only initiated if the patient fails to achieve remission. Step-down therapy advo- cates use of immunomodulators and, at times, biologic agents, in addition to or even before use of steroids and aminosalicylates, in order to achieve remission as soon as possible. These discussions have largely been inspired by the success of step-down therapy in rheumatoid arthritis, success in severely ill patients and in some part by the strong marketing efforts of the pharmaceutical indus- try. Selection of appropriate therapy remains a decision which must be made on an individual basis. The ideal drug for CD should induce and maintain remission quickly and with minimal side effects. There is no such drug right now. Agents such as corticosteroids which are rather good at induc- tion of remission, are not effective in maintenance. Azathioprine and 6-mercaptopurine are the benchmark drugs for maintenance of remission, are not as useful in induction because it takes several months for them to be effective. The benefits of 5-ASA agents in the management of acute CD and the maintenance of remission are questionable.(46, 47, 48) Biologic agents such as Infliximab and Adalimumab, which both induce and maintain remission, are indicated only for patients considered to have moderate to severe disease. 5-Aminosalicylates (5-ASA) Although their benefit is at best questionable, aminosalicylates are often used for patients with mild-to-moderate colitis. The mecha- nism of action of aminosalicylates in CD is not fully understood. In vitro investigation has shown many antiinflammatory and immunosuppressive properties such as inhibition of prostaglan- din and leukotriene synthesis, free radical scavenging, impairment of white cell adhesion and function, and inhibition of cytokine synthesis. Sulfasalazine, initially approved by the FDA in 1950 for rheu- matoid arthritis, has been used for decades in the treatment of Ulcerative Colitis and CD. The drug is broken down by bacteria in the colon into its two products, 5-aminosalicylic acid (5-ASA) and sulfapyridine. These components possess antiinflammatory (5-ASA) and antibiotic (sulfapyridine) properties. 5-ASA acts directly on the colon and is not absorbed while sulfapyridine is mostly absorbed by the intestine and secreted into bile and, to a much lesser extent, into urine. Several clinical trials have shown that Sulfasalazine is more effective than placebo at inducing remis- sion in mild to moderate disease, greatest benefit seen in those with colonic or ileocolonic disease. However, Sulfasalazine has a slower onset of action than prednisone and is considerably less effective. It is not effective as a steroid-sparing agent, and, when used as adjunc- tive therapy, it is not more effective than prednisolone alone. As the sulfapyridine portion of Sulfasalazine accounts for the majority of side effects, several aminosalicylate-containing medications have been created over the years that do not contain sulfapyridine and are thus sulfa free. The most commonly used drug in this class is mesalamine. Several formulations of mesala- mine exist currently, with Asacol, Salofalk, Rowasa, and Pentasa being the most commonly used forms. They are formulated by either using different acrylic resins or by encapsulation in ethyl cellulose micro granules, resulting in delivery of the drug to the distal small bowel and colon. Other forms of mesalamine have Table 32.1 Image tests for Small Bowel CD. Modality Fistula Abscess Stricture Inflammation SBE ++ - ++ ++ Colonoscopy + - ++ ++ US + + + ++ CT enteroclysis ++ ++ ++ ++ MRI ++ ++ ++ ++ WEC - - + ++ DBE - - + ++ PET + + - ++ Scintigraphy + - + ++ Legends: - not useful + somewhat useful ++ very useful  surgery for crohn's disease been created by the dimerization of 5-ASA to make the drug active only once it reaches the colon. Examples of these are olsala- zine (Dipentum), which has two 5-ASAs linked together, and bal- salazide (Colazal), which is 5-ASA linked to an inert unabsorbed molecule. The pharmacology, and thus the undesirable drug absorption rates, differ between these drugs, although the clinical importance of these characteristics is debatable.(49) In general, mesalamine compounds are better tolerated than Sulfasalazine. However, mesalamine has not been found to be an effective treat- ment for induction or maintenance of remission in adequately powered, randomized, placebo-controlled trials.(48) Antibiotics Metronidazole and Ciprofloxacin are the most commonly used antibiotics in treatment of CD. The mechanism of action of anti- biotics in Crohn’s are theorized to include decreased bacterial concentration in the gut lumen, alteration of the microflora com- position to favor beneficial bacteria, decrease in bacterial tissue infection and micro abscesses, decrease in bacterial translocation and systemic dissemination. In addition, some antibiotics act as immunomodulators.(50, 51) These agents have not been found to be efficacious in induc- tion or maintenance of remission. The consensus view is that these agents should be used for perianal fistulas and postoperative man- agement after ileocolic resection or fistula/abscess operation for CD.(52) However, this practice is not based on adequately powered, controlled evidence. In fistulizing Crohn’s disease, antibacterials, immunosuppressive drugs, infliximab, and surgery are often used in combination. Corticosteroids The mechanism of action for this class of drugs in CD is through antiinflammatory activity. Corticosteroid therapy is split into systemic versus nonsystemic types. Conventional systemic cor- ticosteroids such as prednisone and 6-methylprednisolone have demonstrated efficacy in induction of clinical response and remis- sion. It has also been well established that they are ineffective in maintenance of remission. The National Cooperative Crohn’s Disease Study achieved 60% remission, with 0.5–0.75 mg/kg/day prednisone tapered over 17 weeks, compared with 30% on placebo (NNT = 3).(53) The European Co-operative Crohn’s Disease Study achieved 83% remission with 6-methylprednisolone, 1 mg/kg/day over 18 weeks, compared with 38% on placebo (NNT = 2).(54) Nevertheless, approximately 50% of recipients will either fail to respond (steroid-resistant) or will be steroid dependent at 1 year. (55) The use of conventional systemic corticosteroids in patients with clinically quiescent CD does not appear to reduce the risk of relapse over a 24-month period of follow-up.(56) No dose response trial has been performed for prednisone. Treatment is usually started at 40–60 mg daily dose of prednisone and, once response is attained, it is tapered down 5 mg per week. The main disadvantage of sys- temic corticosteroid therapy is its many side effects. Corticosteroids are associated with increased risk for infections, osteoporosis, cata- racts, hyperglycemia, and avascular necrosis of bones. A newer steroid therapy that is widely used for CD is budesonide. Budesonide is a corticosteroid with high affinity for glucocorti- coid receptors but low systemic activity due to extensive first-pass metabolism in the liver. It has been shown to be effective in induc- ing remission in terminal ileal and right-sided colonic disease with significantly less side effects than systemic corticosteroids. A meta-analysis of five published trials found that budesonide was superior to mesalamine and placebo in achieving remission. It was found to be similar in effectiveness to prednisone except for those with severe disease.(57) As for maintenance, an analysis of four double-blind placebo-controlled trials of budesonide with identical protocols revealed that budesonide 6 mg/day is effective for prolonging time to relapse and for significantly reducing rates of relapse at 3 and 6 months, but its effectiveness in maintaining remission is lost when measured at 12 months.(58) Immunomodulators The mechanism of action of these drugs in CD is not thoroughly understood. The most commonly used examples are azathio- prine (AZA) and its metabolite, 6-mercaptopurine (6-MP). AZA and 6-MP have been researched and used successfully since 1971 in patients with CD. AZA is a prodrug that is converted to 6-MP and then metabolized to an active metabolite, 6-Thioguanine Nucleotide (6-TGN). 6-TGN is incorporated into ribonucle- otides, thereby exerting an antiproliferative effect on mitotically active lymphocyte populations. AZA and 6-MP may also possess direct antiinflammatory properties by inhibiting cytotoxic T-cell and natural killer cell function and inducing apoptosis of T cells through Rac1 target gene modulation.(59) Treatment can be initi- ated with either drug at 50 mg/kg, and doses are adjusted while monitoring for toxicity to 1.5–2.5 mg/kg for AZA and 1–2 mg/kg for 6-MP. They are usually administered jointly with steroids for induction of remission due to their relatively slow onset of action; usually 3 months or more.(60) However, they have been found to be effective in maintenance of remission in corticosteroid-induced remission of mild to moderate CD, and in treatment of fistulizing disease. They are also considered to be steroid-sparing agents, an idea supported by a meta-analysis by Pearson et al.(61) The use of AZA in CD has evolved in the past few years with the support of new tests which can predict its toxicity and drug activity. Therapeutic efficacy, bone marrow suppression, and liver toxicity of AZA and 6-MP correlate with concentrations of its metabolite 6-TGN.(62) Thiopurine methyltransferase (TPMT) enzymatically converts 6-MP to 6-methyl-mercaptopurine (6-MMP), diverting metabolism away from 6-TGN. There is an inverse relationship between expression of TPMT and level of 6-TGN. Therefore, lower TPMT activity yielding higher levels of 6-TGN has been associated both with an increased likelihood of clinical response and bone marrow suppression.(59) TPMT deficiency is inherited in an autosomal recessive manner with 1 in 300 subjects having homozygous deficiency, and around 11% of the community hav- ing intermediate enzyme activities.(63) Measurement of TPMT genotype has been proposed to predict the likelihood of toxic- ity to 6-MP or AZA since patients with low TPMT activity are at increased risk of myelosuppression.(64) The strategy of determin- ing TPMT activity in all patients before initiating treatment with AZA could help to minimize the risk of myelotoxicity, as patients with intermediate TPMT activity had fourfold more risk than high TPMT activity patients.(65) It is currently recommended to test all patients’ TPMT levels before treating with AZA/6-MP. . allows influx of intestinal fluid, which in turn dissolves the lactose in a predetermined amount of time. If the capsule is retained in the gastrointestinal tract, it disintegrates into small,. proximal obstruction. (X-ray courtesy of Department of radiology Cleveland Clinic Florida) (A) (B) (C)  improved outcomes in colon and rectal surgery Colonoscopy Approximately 50 percent of. altered in CD, allowing white cells to cross the intestinal wall. Activated leukocytes infiltrate the mucosa and can be detected in feces. Lactoferrin is an iron-binding glycoprotein found