Crohn's diseases topic of general surgery

Topic of general surgery
MBBS

1. Crohn’s Disease Dr A Sushmitha

2. Inflammatory bowl disease – idiopathic disease caused by disregulated immune response to host intestinal microorganisms which pursue a prolonged relapsing and remitting course. Mainly 2 types Crohn’s disease Ulcerative colitis

3. Cronh’s Disease Definition Crohn’s disease is a chronic, transmural inflammatory disease of the gastrointestinal tract Can involve any part of the alimentary tract from the mouth to the anus Most commonly affects the small intestine and colon

4. History In 1761, Morgagni, first described a case of inflamed ileum with perforation and thickened mesentery in a young m a n with a history of diarrhea and fever. In 1913, the Scottish surgeon Dalziel described nine cases of intestinal inflammatory disease. In 1932, Crohn and his colleagues, detailed the pathologic and clinical findings of this inflammatory disease in young adults.

5. Epidemiology Annual incidence - 8 per 100,000 ( North America and Northern Europe ) Highest prevalence seen in American Whites and Northern Europeans than those originating from Central Europe, South America, Asia and Africa. CD primarily attacks in the 2 nd or 3 rd decades of life and 2 nd peak occurring in the 6 th decade of life. Genders are equally affected.

6. Risk factors Patient factors- age, sex, smoking Genetic factors Environmental factors- urban or industrial areas, high latitudes, NSAID’s, Antibiotics , Infection, diet

7. Risk Factors Increase in risk with Smoking – 2 times , and increases severity, need for surgery, recurrence Siblings – 30 times First degree relatives – 14-15 times CD have shown concordance rate of 3.7% in Dizygotic twins and 67% in Monozygotic twins I ntestinal microflora and epigenetic changes induced by environmental factors play an important role in disease development and progression in genetically susceptible individuals.

8. Aetiology CD is incompletely understood but is thought to involve a complex interplay of genetic and environmental factors. Infectious agent – Mycobacterium paratuberculosis - PCR techniques have confirmed the presence of mycobacteria but antimicro bial ther apy has not been effective. E nteroadherent E.coli. - an increased number of E. coli has been associated with a shorter time before relapse of the disease.

9. Aetiology Genetic factors - CARD15 gene – Strongly associated with CD NOD2 gene – Increased and earlier need of surgery in CD FHIT gene – Tumor suppressor gene, plays a role in pathogensis , development and progression of CD related cancers. ATG16L1 g ene – associated with a synergistic increase in earlier onset and disease severity, especially in smokers.

10. Pathogenesis Patients with a genetic predisposition, exposure to particular environmental stimuli triggers an altered immune response, resulting in inflammation and ulceration of intestinal tissues.

11. Pathogenesis Increase in gut permeability with abnormal immune-mediated response to colonisation of the gut with some subspecies of the normal enteric microflora, may initiate the disease . Increased gut mucosal permeability Increased Passage of luminal antigens Cell mediated inflammatory response Release of proinflammatory cytokins such as IL-1, IL-2, IL-8 and TNF α Local and systemic inflammatory responses

12. Pathogenesis TNF- alpha induces Angiogenesis Panneth cell necrosis Intestinal epithelial cell death and impaired barrier function Increase in immune response Myofibril induced tissue destruction CD is associated with a defect in suppressor T-cells, which usually act to prevent escalation of the inflammatory process.

13. Pathology The involvement of the large and small intestine - 55% Small bowel disease alone – 30% Large bowel disease alone – 15% Perianal disease - 25% of patients with CD limited to small intestine - 41% of patients with ileocolitis - 48% of patients with colonic involvement alone - 5% of patients, sole presenting feature

14. Pathology Other sites of GIT – rare In patients with colonic disease, rectal sparing is characteristic of Crohn’s disease and helps distinguish it from ulcerative colitis.

15. Gross Pathology Initially superficial aphthous ulcer are seen, which becomes transmural, characteristically linear and may coalesce to produce transverse sinuses with islands of normal mucosa in between, giving the characteristic cobblestone appearances. Extensive fat wrapping caused by the circumferential growth of the mesenteric fat around the bowel wall Bowel wall becomes increasingly thickened, firm, rubbery, and almost incompressible Involved segments often are adherent to adjacent intestinal loops or other viscera, with internal fistulas

16. Gross Pathology The mesentery of the involved segment is thickened, with enlarged lymph nodes CD is characteristically discontinuous, with inflamed areas separated by normal intestine, called skip lesions .

17. Microscopic features A chronic inflammatory infiltrate present in the mucosa and submucosa showing extensive edema, hyperemia, lymphangiectasia, intense infiltration of mononuclear cells, and lymphoid hyperplasia . CD are noncaseating granulomas with Langerhans giant cells found in the wall of the bowel or in regional lymph nodes in 60% to 70% of patients, most common in anorectal disease.

18. Noncaseating granuloma in the muscular layer of small bowel

19. Patterns of disease Three general entities Stricturing CD – Fibrotic scar tissue constricts the intestinal lumen resulting in partial or complete obstruction. Perforating CD – Caused by deep mucosal ulceration that can develop into sinus tracts, fistulas and abscesses. Inflammatory CD – Mucosal ulceration and bowel wall thickening may lead to an adynamic segment of intestine with luminal narrowing causing obstructive symptoms in the small intestine and diarrhea in colon.

20. Clinical features Insidious onset with slow and prolonged course There are symptomatic periods of abdominal pain and diarrhea with asymptomatic periods of varying lengths. Abdominal Pain - Most common- lower abdominal pain, intermittent and colicky (ileal inflammation mimics acute appendicitis) Diarrhea - Intermittent, fewer bowel movements, stools rarely contain mucus, pus or blood. Intermittent fevers, weight loss and secondary anemia are common.

21. Vienna classification Vienna classification divides patients into 24 distinct categories, it provides staging of the disease, to help predict remission and relapse, and to direct therapy

22. Clinical features CD of Foregut – Oral Crohns – Aphthous ulcers in the hard palate. Esophageal Crohns – Nausea, vomiting, dysphagia or odynophagia Stomach and duodenum – mimics peptic ulcer disease, obstructive in nature Crohns colitis – May d evelop toxic megacolon and present with a marked colonic dilation, abdominal tenderness, fever, and leukocytosis.

23. Clinical features The rectal mucosa is often spared in CD, if involved it will feel thickened, nodular and irregular. Perianal Disease – fissure, fistula, stricture or abscess, hypertrophic perianal skin tags Incontinence may develop as a result of destruction of the anal sphincter musculature because of inflammation, abscess formation, fibrotic change and repeated episodes of surgical drainage. In severe cases, the perineum may become densely fibrotic, rigid and covered with multiple discharging openings - watering can perineum

24. Complications Obstruction – Chronic fibrosing lesions, strictures Perforations - Intra-abdominal abscesses or peritonitis Fistulae – Enteroenteric Ileo sigmoidal Ileo-vesical Entero- cutenous Long-standing Crohn’s disease predisposes to cancer, more common in the ileum. Extraintestinal cancer, like squamous cell carcinoma of the vulva and anal canal and Hodgkin and non-Hodgkin lymphomas, may be more frequent in patients with Crohn’s disease .

25. Extraintestinal manifestations of Crohn’s disease In Crohn’s disease patients incidence of these diseases are more than in general population. Most common fatty infiltrations in liver 40-50%, Cirrhosis 2-5% Related to disease activity Erythema nodosum – 5-15% Pyoderma gangrenosum Arthropathy Eye complications (iritis/uveitis) – 10% Aphthous ulceration Amyloidosis

26. Others- Gallstones Renal calculi Primary sclerosing cholangitis Chronic active hepatitis Sacroiliitis

27. Diagnosis Clinical suspicion based on history and clinical features and examination Investigations- laboratory and imaging

28. Lab Investigations Full blood count Anemia Malabsorption Blood chemistry Decrease in albumin ESR/CRP- inflammatory markers elevated in active disease Microscopic culture and sensitivity Stool sample to rule out bacterial or parasitic involvement

29. Lab Investigations Serologic markers Perinuclear antineutrophil cytoplasmic antibody, Anti–Saccharomyces cerevisiae antibody (ASCA) Outer membrane porin of flagellin (anti-CBir1) Outer membrane porin of E. coli ( OmpC -IgG) Stool lactoferrin and Fecal calprotectin Diagnosis of CD with new onset of GI symptoms and to predict risk of clinical recurrence.

30. Imaging Barium contrast studies Shows cobblestone appearance of the mucosa composed of linear ulcers, transverse sinuses, and clefts. Shows areas of structuring and prestenotic dilatation. Long lengths of narrowed terminal ileum ( Kantor string sign ), present in long-standing disease. Segmental and irregular patterns of bowel involvement. Fistulas between adjacent bowel loops and organs.

31. Imaging CT with Oral contrast Thickened and dilated intestinal loops Inflammatory masses Abscesses Hydronephrosis resulting from retroperitoneal fibrosis and ureteral narrowing

32. Imaging MRI Complex perianal disease Detecting intestinal strictures and ileal wall enhancement. MRI entroclysis is a useful intestinal strictures as well as fistulas and sinus tracks Fistulography Anatomy and complexity of the fistulae and allow adequate planning for future surgery.

33. Endoscopy Earliest findings are of aphthous ulcers surrounded by a rim of erythematous mucosa. Areas of normal mucosa in between areas of inflammation that are irregular and ulcerated, with a mucopurulent exudate. Irregular Crohn’s stricture with polypoid mucosa may be almost macroscopically indistinguishable from malignancy. Recurrent disease usually presents first with aphthous ulceration just proximal to the anastomosis.

34. Capsule Endoscopy – Patients with evidence of chronic GI symptoms or blood loss where no evidence of ulceration can be found with more conventional endoscopic assessment. Upper GI Endoscopy - Deep longitudinal ulcers and cobblestoning of mucosa in the duodenum, stomach or, rarely, in the oesophagus .

35. Medical Management Medical Treatment - Inducing and maintaining remission as well as acute exacerbations or complication of the disease. Corticosteroids Aminosalicylates Antibiotics Immunomodulators Monoclonal antibodies

36. Medical Management Steroids Induce remission in 70-80% of cases with moderate to severe disease. Prednisolone (40-60 mg /day) – Used until resolution of symptoms. Calcium and Vitamin D Supplimentation initiated to prevent steroid induced loss of bone mineral density. Budesonide (9 mg/day) – 1 st line therapy with mild to moderate active CD with localized ilial disease.

37. Medical Management Aminosalicylates Effective in small bowel CD. Mesalamine (slow release o 5 ASA) – post operative maintenance (4mg/day). Antibiotics Not use ful for maintenance or to induce remission Role in septic complications and secondary infections associated with CD Perianal disease, Enterocutanous fistulas Metronidazole and Ciprofloxacin maybe used in perianal disease.

38. Medical Management Immunomodulatory agents Used for maintenance and treatment of moderate to severe CD. Azathioprine and 6-MP – effective for maintaining steroid induced remission IV MTX – effective for steroid dependent and refractory Crohns Deficient TPMT (Thiopurine Methyl Transferase ) cause inefficient metabolism of 6-MP, increased risk of fatal bone marrow suppression. Cyclosporine & FK-506 - used in severe disease who do not respond to IV steroids.

39. Medical Management Monoclonal antibody therapy - Used for maintenance Infliximab Murine chimeric monoclonal antibody against TNF- α G iven IV infusion every 8 weeks for maintenance of remission Adalimumab Humanized IgG1 monoclonal antibody Given subcutanously every 1-2 weeks depending on response

40. Medical Management Certolizumab Humanized antibody fragment ideal in pregnant and nursing women Vedulizumab - More gut specific with less side effects Ustekinumab – used in severe Crohns disease refractory to anti-TNF Therapy Early and aggressive use of these agents in patients at high risk for early recrudescent disease after surgery, may reduce need of subsequent surgery. Contraindicated in active infections, TB and past history of malignancy.

41. Therapies in Crohns Disease

42. Nutritional Therapy Only for maintenance Patients with IBD are often malnourished. Abdominal pain and obstructive symptoms may decrease oral intake. Diarrhea causes significant protein loss Chemically defined elemental diets – reduce disease activity particularly in patients with disease localized to small bowel. Advantages – Replenish depleted nutrient stores Allow intestinal protein synthesis and healing Prepare patients for operation Disadvantages – Rapid relapse

43. Surgery for CD Surgery doesn’t cure CD Principle – Managing complications – Preserve Health Gut and maintain adequate function 70% of patients will require surgical resection in 1 st decade after diagnosis Main role of surgery is to relieve obstruction ( only grossly inflamed tissue is removed) Open surgery- ostomy / stricherplasty / bypass surgery laproscopic surgery

44. Indications for Surgery Emergency indications Recurrent intestinal obstruction Free perforation of the bowel Elective indications Failure of medical therapy Steroid dependent disease Intestinal fistula Persistent or, less commonly, massive acute bleeding Perianal disease (abscess, fistula, stenosis) Malignant change (notably in the colon and less commonly as a complication of small bowel disease).

45. Acute inflammatory presents with complications fistula / intra abdominal abscess Intra abdominal abscess – CT guided percutaneous drainage Fistula – Require resection of segment of bowel with active crohns disease Secondary site of fistula are often normal and do not require resection, simple closure is sufficient

46. Chronic fibrotic Crohns presents with stricture Stricture - Resection / strictureplasty Endoscopic Dilatation Balloon dilatation of fibrostenotic disease, provided stricture reached with an endoscope, shows symptomatic improvement Contraindicated in ulcerated / inflamed stricture brotic

47. Strictureplasty Done in patients with multiple short areas of narrowing present over long segments of intestine Several previous resection of small intestine Areas of narrowing caused by fibrous obstruction Full thickness biopsy with frozen section of stricture done at surgery because of risk of development of carcinoma at chronically strictured site.

48. Strictureplasty Contraindications of Strictureplasty Excessive tension due to rigid and thickened bowel segments Perforation of the intestine Fistula or abscess formation at the intended strictureplasty site Hemorrhagic strictures Multiple strictures within a short segment Malnutrition or hypoalbuminemia (<2.0 g/dL) Suspicion of cancer at the intended strictureplasty site

49. Strictureplasty

50. Small Bowel Crohns Disease Acute ileitis- patient with acute appendicitis symptoms, on exploration if appendix is normal, Appendectomy should be performed, intestinal resection should not be performed Ileo caecal resection – terminal ileal disease Segmental resection with or without primary anastomosis – done for intestinal obstruction Anastomosis- wider anastomosis to prevent recurrence

51. Contraindications of re anastomosis Current high-dose steroid therapy (≥10 mg prednisolone for ≥4 weeks before surgery) Current preoperative monoclonal antibody therapy Preoperative significant weight loss (>10% premorbid weight) Pre-existing abdominal sepsis (notably abscess or fistula) Serum albumin <32 g/L Hemodynamically unstable Patients with extensive intraabdominal contamination

52. Crohns Colitis Surgery done when not responding to medical management and complication which includes obstruction, hemorrhage, perforation and toxic megacolan . Depending on diseased segment Segmental colectomy with colocolonic anastomosis Subtotal colectomy with ileoproctostomy In patients with extensive perianal and rectal disease, total proctocolectomy with Brooke ileostomy.

53. Crohns Colitis Risk of cancer is same as ulcerative colitis Annual surveillance colonoscopy with multiple biopsies recommended in patients with long standing CD ( greater than 7 years)

54. Perianal Disease Skin Tags, fissures - Medically managed ( Surgery contraindicated because of risk of chronic, nonhealing wound, incontinence) Excision / Sphincter otomy Non cutting setons - used in high Transsphicteric , extrasphincteric , suprasphincteric fistulas to avoid sphincter injury Fistulotomy - superficial, low trans- sphincteric fistulas and low intersphincteric fistulas

55. Laparoscopic Surgery in CD Done in localized abscess, simple intraabdominal fistulas, perianastomotic recurrent disease and disease limited to distal ileum. Advantages – Shorter median operative time Earlier return of bowel function Shorter hospital stay Less incidence of incisional hernia Disadvantage – Difficult to asses the full length of small intestine. Rate of disease recurrence is similar to that of open surgery

56. Prognosis Postoperative prophylaxis based on effectiveness of treatment

57. Crohn’s disease Vs Ulcerative colitis Crohns disease Ulcerative colitis RISK FACTORS Smoking Genetics factors Environmental factors- Urbans , high latitudes, NSAID’s, Antibiotics, Diet, Infection , Inflammation Genetic factors Environmental factors PROTECTIVE FACTORS _ Smoking Appendectomy PATHOGENESIS Most commonly disoredered response to intestinal bacteria Most commonly Autoimmune response LOCATION Anywhere in GIT, most common small intestine and colon Skip lesions, rectal sparring Perianal involvement present Colon ( Proctosigmoiditis , left sided colitis, pancolitis , backwash ileitis GROSS MORPHOLOGY Early- aphthous ulcer Later- deep linear ulcers Cobblestone appearance of mucosa Extensive fat wrapping around bowel, thickened mesentry with enlarged lymph nodes Hyperemic mucosa Superficial ulcers Pseudopolyps MICROSCOPIC MORPHOLOGY Transmural inflammation Noncaseating granulomas and lymphoid aggregates Mucosal inflammation Cryptitis , crypt abscess INTESTINAL FEATURES Abdominal pain, Diarrhoea (rarely blood in stools) Strictures, Fistulas Rectal bleeding, diarrhoea Fulminant colitis ( tenesmus , crampy abdominal pain) constipation

58. Crohns disease U l c e r a t i v e c o l i t i s EXTRAINTESTINAL FEATURES Erythema nodosum , Pyoderma gangrenosum , arthritis, iritis/ uveitis, sacroilitis , ankylosing spondylitis Gallstones, renal Caliculi , primary sclerosing cholangitis Arthritis Erythema nodosum , Pyoderma gangrenosum , ankylosing spondylitis, primary sclerosing cholangitis COMPLICATIONS Obstruction, perforation, fistulae, Long standing case- carcinomatous Post operative recurrence Massive hemorrhage Toxic megacolon INVESTIGATIONS Serological markers- ASCA Endoscopy- discontinuous lesions Barium contrast- kantor string sign Endoscopy- continuous lesions Barium enema- fine mucosal granularity Toxic megacolon MEDICAL MANAGEMENT Corticosteroids ( Prednisolone, Budesonide ) 5-ASA agents, Antibiotics Immunomodulatoes ( Azathioprine, 6-MP, MTX) Anti-TNF alpha agents- Infliximab , Adalimumab , certolizumab , vedulizumab 5-ASA agents, Corticosteroids Thiopurines Anti-TNF therapy SURGICAL MANAGEMENT Segmental resection with or without reanastomosis , stricherplasty , bypass surgery Colectomy and ileorectal anastomosis Total proctocolectomy with end ileostomy/ ileal anal pouch anastomosis

59. Crohns disease V s u l c e r a t i v e c o l i t i s

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