Inflammatory Bowel Disease

This is comprehensive Presentation about IBD, its Classification, major subtypes, eitology, genetics, presentation, diagnosis and treatment.
it Includes Both Crohn's Disease And Ulcerative Colitis in detail
Pathology, Diagnosis, Medical Therapy, Surgical Management of Both the diseases are described

1. Inflammatory Bowel Disease Dr. Vikas V Sugery Pg Dept of General Surgery MMCR&I, MYSORE

2. Definition Conditions characterized by presence of IDIOPATHIC Intestinal Inflammation .                                                                   - Bailey & Love Chronic Condition resulting from Inappropriate Mucosal Immune Activation                                                                    - Robbins & Cotran Inflammatory Bowel Disease includes : A] Crohn's Disease                  B] Ulcerative Colitis            C] Indeterminate Colitis

3. Introduction In 85 % cases IBD can be differentiated into Ulcerative Colitis (UC) or Crohn's Disease (CD) based on : Distribution of Affected Sites Morphological expression of Disease  In 15%  cases, differentiation is impossible; these patients are classified as having Indeterminate Colitis .

4. Major Types of IBD Crohn's Disease CROHN’S DISEASE is a Chronic, Idiopathic Transmural Inflammatory disease with Skip Lesions that may affect ANY part of the alimentary tract, although there is propensity to affect the D istal S mall B owel . - Schwartz Principles of Surgery 11th edition Ulcerative Colitis ULCERATIVE COLITIS is a C hronic Inflammatory dis ease that a ff ects the Mucosa and S uperficial S ubmucosa of the R ectum and colon -M aingot‘s A bdominal O perations 1 3 th edition

5. HISTORY OF CROHN’S

6. Earliest  bona-fide case of CD in Sweden 191 3   13 Y/M Operated for Suspected Appendicitis Bypass Procedure – due to Stenosis Of Terminal Ileum  Dismissed Diagnosis of TB 1969 Admitted For Perianal Fistulas - Bari u m Enema – Difficult to Interpret Laparotomy + Resection  of Bypassed Segment of Ileum  Subsequent HPE – Changes Typical of CROHN'S Disease

7. Epidemiology Source : Harrison Prinicples of Internal Medicine 20th Edition

8. Epidemiology Peak incidence of UC and CD is in the 2nd to 4th decades , Incidence among those age 20–29 years old :  78% of CD studies   51% of UC studies   A second modest rise in incidence - between the 7th & 9th decades of life. The female-to-male ratio ranges from  0.51 to 1.58 for UC studies and 0.34 to 1.65 for CD studies,  Hence diagnosis of IBD NOT Gender-specific . Pediatric IBD ~20–25% of all IBD patients 5% of all IBD patients are <10 years of age

9. Background of the disease IBD exact Cause UNKNOWN. But believed to be a combination of : Genetic Factors Mucosal Immune Response Environmental Factors Inappropriate Inflammatory Response to Intestinal bacteria in Genetically Susceptible Individuals leading to a Sustained Mucosal Inflammatory Response that the Host is Unable to Downregulate . Some evidence - Bacterial & Viral infections are a/w IBD, BUT No Specific Species implicated. There are 2 Basic Components to the Immune Response : Innate & Adaptive

10. Innate Immunity Initial Response to invading pathogens Main Components: Epithelial barrier & Phagocytes within the lamina propria Protective effect is limited because NO MEMORY Immune Response- Not sed on Reinfection Initial response - Inadequate and Initiates This Process In IBD Adaptive Immunity Mediated by Lymphocytes, T and B cells , that express antigen receptors on their surface Cytokines - produced by T cells - Eradicate infection and also give rise to Memory Cells - Prevent Reinfection In IBD , different subset of T Cells produce - Interleukin 13 (IL-13) & IFN- Gamma resulting in Epithelial dysfunction, Antibody production, and Immune complex formation

11. T ridirectional relationship between C ommensal F lora (microbiota), I ntestinal E pithelial cells (IECs), M ucosal I mmune S ystem is dysregulated, leading to C hronic I nflammation A ffected by G enetic and E nvironmental factors Pathogenes I s of IBD

12. CD UC

13. CROHN'S DISEASE

14. GEnetic Factors - Crohn’s CARD15/NOD2  gene mapped to chromosome 16q12. -BACT SENSING & AUTOPHAGY CARD15 - Inn ate immunity - P referentially expressed to Paneth’s cells of the I leum .  CARD 15 - Production of proinflammatory cytokines in response to gut microbes. Mutations of CARD15 are neither necessary nor sufficient to contract this disease. ATG16L1 gene - Immune response to muramyl dipeptide, a component of both GRAM +VE and GRAM -VE bacteria – AUTOPHAGY Gene NOD2 polymorphisms ATG16L1 Strong Association With Fibro-Stenosing CD   Fistulizing CD

15. CroHn's Disease - Regional Enteritis Involvement : Can affect ANY part of the GI tract from MOUTH to ANUS 80% of patients small bowel involvement : Terminal ileum is involved in 90% . 30–40% of patients have small bowel disease alone 40-55% - Involves Both Small & Large Bowel 30% having Terminal Ileitis Alone 15–25% have Colitis alone Rectum is often spared in CD Higher socioeconomic status - Increased risk of Crohn’s disease Breastfeeding - Protective against the development of Crohn’s disease. Crohn’s disease is More Prevalent among Smokers . Furthermore, Smoking is associated with the Increased risk for both the Need for Surgery and the Risk of Relapse after Surgery for Crohn’s disease.

16. Pathology Pathological hallmark - Focal, Transmural inflammation with Multiple Lymphoid Aggregates in a thickened edematous fibrotic Submucosa & Muscularis Propria . Noncaseating granulomas - valuable Diagnostic Feature Seen only in 50% of resected specimens (Maingot's) ; 70% of resected specimens (Schwartz) Rarely seen on Endoscopic Biopsies Earliest Gross Manifestation - small mucosal ulcerations call Aphthous Ulcers . 3 mm in diameter and surrounded by a Halo of Erythema Typically Arise Over Lymphoid Aggregates Aphthae coalesce into larger, stellate shaped ulcers Longitudinal Fusion - Linear / Serpenginous Ulcers Transverse Fusion - Cobblestone Appearance of Mucosa

17. NORMAL

18. Fig : Gross : The middle portion of bowel seen here has a thickened wall, and the mucosa has lost the regular folds and contains deep fissures. The serosal surface shows reddish indurated adipose tissue that creeps over the surface.

19. Pathology - Crohn's Continued Focal inflammation → Fistula Tracts → Resolves by Fibrosis → Stricturing of Bowel Skip Lesions - Separated by intervening Normal-appearing intestine Bowel wall → Thickened , Fibrotic → Chronic Recurrent Bowel Obstruction Thickened mesentery → Projections into bowel (‘ Creeping Fat ’) / Fat Wrapping (pathognomonic) Serosa & Mesentery inflammation → Adhesion of the Inflamed bowel to other loops of Bowel or Other Adjacent Organs. Transmural Involvement : Lead to : Intra-Abdominal Abscesses, Fistulas , and, rarely, free perforation

20. FIG : Histology Showing Mucosal Ulceration & Destruction FIG : Histology Shows Non Caseating Granuloma

21. Source : Maingot's abdominal Operations 13th edition

22. CLINICAL PRESENTATION Vary greatly depending on the Segment of Intestine involved. Crohn’s disease can be categorized into three general manifestations: A] Inflammatory disease B] Stricturing disease C] Perforating disease . Do not represent truly distinct forms of disease; used to describe the predominant gross manifestation of the disease More than one pattern tends to occur in same patient or even same segment of intestine. Even so, one pattern tends to predominate .

23. INFLAMMATORY PATTERN Mucosal ulceration and Bowel Wall Thickening Edema - lead to an Adynamic segment of Intestine and Luminal narrowing . Obstructive symptoms in the Small Intestine Diarrhea in the Colon . Of the three patterns of Crohn’s disease, the Inflammatory pattern is much more likely to respond to Medical Therapy .

24. STRICTURING PATTERN Chronic inflammation → Fibrotic scar tissue → constricts the intestinal lumen with cicatricial strictures [“Fibrostenotic lesions.”] Develop Partial or Complete Intestinal Obstruction , and hence their symptoms are primarily obstructive in nature. Not Reversible with Medical Therapy Once Fibrostenotic areas become symptomatic , significant improvement rarely occurs and Surgical intervention is often required

25. PERFORATING PATTERN Development of Sinus tracts , Fistulas , and Abscesses . Penetrating Sinus tracts - deep mucosal ulcerations. Abscess - Penetrate through the muscularis propria Fistulas -When Penetrate into surrounding structures Free perforation with spillage of intestinal contents into the abdominal cavity is NOT a common phenomenon. Perforating disease is accompanied by a degree of Stricture Formation .

26. Crohn's Disease - Distinguising Features

27. Aggressive fistulizing disease Fistulas are manifestations of the Transmural Nature of CD Perianal Fistulas are common and occur in 15% to 35% of patients. Enterovaginal fistulas occur in women. Entero-Vesicular - recurrent polymicrobial UTI or as Frank Pneumaturia and Fecaluria . Entero-Cutaneous fistula after Appendectomy. Other types- Entero-Enteric, Entero-Colonic, and Colo-Colonic fistulas

28. BLADDER

29. Location of Disease GASTRODUODENAL AND ESOPHAGEAL CROHN'S CROHN’S DISEASE OF THE SMALL INTESTINE CROHN’S COLITIS EXTRAINTESTINAL CROHN’S DISEASE Occular : Uveitis & Episcleritis Dermatological : Erythema Nodosum & Pyoderma Gangrenosum Hepatobiliary : Primary Sclerosing Cholangitis, Gallstones Joint disorders : Ankylosing Spondylitis , Sacroilitis Seronegative Polyarteritis,

30. Gastroduodenal and Oesophageal CROHNS DISEASE Esophageal - < 2% of patients. Dysphagia, Odynophagia, Substernal Chest pain, and Heartburn Mouth ulcers - aphthous ulcers - Hard Palate, Esophageal Ulcers . Esophageal stricture and esophagobronchial fistula Gastroduodenal - ( Focal gastritis , Duodenitis with or without granulomas) H-pylori-negative peptic ulcer disease , dyspepsia or epigastric pain as the primary symptoms. Symptoms usually related to the Obstructive nature of the disease with delayed gastric emptying, a sense of postprandial gastric fullness, nausea, and vomiting.

31. FIG :“notching” of the duodenal folds protruding lesions in the bulb and second duodenal portion a “bamboo-joint-like (BJL)” appearance. FIG :Pre-pyloric gastric ulcer in pt with Crohn’s disease

32. Crohns Disease of Small Intestine Pain abdomen - 90% of cases Result of obstructive or septic complications. Partial obstruction - Pain Abd - Postprandial and Crampy in nature Septic complications - Pain Abd - Steady and Associated with fevers. Weight loss Food avoidance / Result of Malabsorption RLQ Palpable mass - Abscess or Phlegmon in Perforating disease Thickened loop of intestine in Obstructive disease Evidence of Fistulization to the skin, urinary bladder, or vagina

33. Crohns Disease of Small Intestine Ileocolitis Recurrent Right Lower Quadrant Pain and non bloody diarrhoea Tender palpable mass in RIF , fever and leucocytosis Pain is colickly and Relieved by defecation May Present as Small Bowel Obstruction Jejunoileitis A/W loss of digestive and absorptive surface Malabsorption and steatorrhoea Anemia, Hypoalbuminemia, Hypocalcemia, Hyperoxaluria

34. CROHN’S COLITIS Diarrhea that may or may not be bloody. Acute Flares : fever and Abdominal Pain Excacerbated by Bowel Movements Stricturing - Advanced disease - Colonic Obstruction. Abscess Formation + Fistula Formation Very Rarely - Toxic MegaColon can occur ( Less Frequent than UC)

35. PERINEAL CROHN’S DISEASE 40% of patients will develop perineal manifestations . Isolated Perineal and Anorectal disease occurs in 5% to 10% of affected patients Frequently affects the Anal Crypts and gives rise to Perianal Fistulas, Abscesses, and Anal Strictures . Associated with Hypertrophic Perianal Skin Tags , Fissures , and Perineal Scarring

36. Extra Intestinal Manifestations of Crohn's

37. Extra intestinal Manifestations of Crohns Peripheral Polyarteritis, Episcleritis, Uveitis and Erythema Nodosum → correlate with the activity of Intestinal Crohn's disease These Regress with complete surgical resection of the affected segment of intestine or with successful medical control of the intestinal inflammation Clinical course of Ankylosing Spondylitis and Primary Sclerosing Cholangitis → Independent of the level of disease activity → Do not improve with Surgical Resection of affected Segment of Bowel Pyoderma gangrenosum - Inconsistent Data.

38. Dermatalogical Pyoderma gangrenosum Erythema nodosum Granulomatous inflammation of the skin Aphthous ulcers of the mouth Angular cheilitis

39. Pyoderma Gangrenosum Fig: Pyoderma gangrenosum presents as ulcerated lesions that appear independent of disease activity, and is more difficult to treat PYODERMA GANGRENOSUM Fig : Typically appears as Painful, Red, Subcutaneous Nodules on Extensor Surfaces and mirrors disease activity ERYTHEMA NODOSUM

40. Musculoskeletal Clubbing Arthritic manifestations Peripheral Arthropathy - 16% to 20% Pauciarticular arthropathy (type I, affecting four or fewer joints) Polyarticular arthropathy (type II, with five or more joints affected) Axial arthropathies - 3% to 10% Metabolic bone disease Granulomatous vasculitis, periostitis and amyloidosis

41. Ocular Manifestations Occur in 6% of patients . Episcleritis Scleritis Uveitis - the anterior segment Keratopathy and night blindness FIG: Episcleritis -Inflammation of the Vascular layer directly beneath the Conjunctiva Fig : Scleritis - Inflammation of Deeper Scleral vessels. May involve Vision changes

42. Hepatobiliary Gallstones Asymptomatic and mild elevations of liver biochemical tests PSC more often is associated with UC > CD (RARE) Autoimmune hepatitis . Venous thromboembolism Arterial thrombosis. Vascular PRIMARY SCLEROSING CHOLANGITIS Intra-hepatic & extrahepatic bile duct inflammation & fibrosis. In 5% UC pts., less in CD. Both PSC & IBD are usually pANCA (+)ve. Gold standardis ERCP. MRCP is more sensitive, specific & safer. Gallbladder polyps have high risk of malignancy. Symptomatic patients develop liver failure within 5-10 yrs needing transplant

43. Renal and Genitourinary Inflammatory entrapment of the ureter Uric acid and oxalate stones. Membranous nephropathy & Glomerulonephritis Renal amyloidosis . Penile and vulvar edema

44. Diagnosis No single symptom, sign, or diagnostic test establishes the diagnosis of Crohn’s disease. Serologic and Inflammatory markers are typically elevated and correlate with disease activity . Ex : C- Reactive Protein , Calprotectin , ESR Fecal calprotectin and Lactoferrin levels have been used to distinguish IBD from irritable bowel syndrome (IBS), assess whether CD is active. 2% to 28% of patients : p - ANCA Positive ; ASCA Positive found in 39% to 69% patients Should be excluded : Acute ileitis caused by Campylobacter and Yersinia species Typhoid enteritis caused by Salmonella typhosa Mycobacterium tuberculosis - Terminal Ileum Involvement Cytomegalovirus (CMV) can cause Intestinal ulcers, bleeding, and perforation

45. Diagnosis Colonoscopy - with intubation of Terminal Ileum is the main diagnostic tool. Cobblestone appearance - Focal Ulcerations adjacent to areas of Normal Appearing Mucosa along with polypoid mucosal changes Skip areas of involvement, Rectal Sparing Pseudopolyps , as seen in ulcerative colitis, are also often present. Opportunity for a biopsy for histologic evaluation

46. Imaging Barium small bowel follow-through , CT enterography , or MR enterography - contrast examinations of small bowel to Reveal Strictures , Ulcers & Fistulas . Early Disease : Mucosal Granulations with Ulceration and Nodularity Progression of Disease : Thickening of Mucosal Folds and Edema of the bowel wall. Advanced Disease : Cobblestone Appearance CT - Helps in identifying Abscess / Inflammatory mass / Other Intra Abd disorders Enteric fistulas including ileosigmoid and ileovesical fistulas are not typically demonstrated on contrast radiography - Demosstrated well in CT-Entergraphy CTE combined with Ileocolonoscopy as a First-line Test for Diagnosis & Staging of Crohn’s .

47. Fig: Small bowel radiograph demonstrating Crohn’s disease of the terminal ileum Fig: Small bowel radiograph demonstrating Crohn’s disease of the terminal ileum with high-grade strictures and ulcerations.

48. Fig: CobbleStone Appearance :Small bowel radiograph demonstrating Crohn’s disease with strictures in the jejunum. Fig: String Sign of Kantour : Long segment of narrowed terminal ileum in a 'string like' configuration in keeping with long stricture segment

49. MR enterography Intestinal wall thickening , Submucosal edema , Vasa recta engorgement , and lymphadenopathy are signs of Active disease FIESTA (Fast Imaging Employing Steady-state Acquisition) images can add information regarding the functional status of fibrotic segment . MRI images yield a diagnostic accuracy of 91%.

50. Capsule Endoscopy Patient Swallows encapsulated video camera Transmits an image to a receiver outside the pt. It is most commonly used for finding Obscure sources of GI blood loss , The images can find Ulcerations associated with CD if endoscopy and colonoscopy are unrevealing. The major risk is the potential to get lodged at the point of a stricture!

51. DIFFERENTIAL DIAGNOSIS : Small bowel Crohn's Irritable Bowel syndrome ; Acute appendicitis ; Intestinal Ischemia ; Pelvic Inflammatory Disease ; Gynecologic malignancies Radiation enteritis, Yersinia Infections, Intestinal injury from NSAIDs ; Intestinal Tuberculosis, Small Bowel Tumors Most important : A] Small Bowel Malignancy B] Intestinal TB Small Bowel Malignancy suspected - Resection should be undertaken to make certain the diagnosis. TB - Exposure to TB, PPD Skin test, Chest X ray . If Latent Tb + Crohn's → should be treated for TB prior to Immmunosuppresive Therapy for CROHN'S

52. DIFFERENTIAL DIAGNOSIS : Crohn's Disease of COlon Ulcerative colitis ; Infectious Colitis ; Collagenous Colitis ; Ischemic colitis ; Diverticular Disease ; Colonic Neoplasm ; Solitary Rectal Ulcer Syndrome ; NSAID colopathy Difficult to Differentiate from Ulcerative Colitis As it is Possible for Crohn’s disease of the colon to Reproduce all the features of ulcerative colitis After a complete history and Physical examination complemented by appropriate radiologic, endoscopic, Blood investigations - Differentiated in 85% case Rest Cases - 15% - Inderminate Colitis

53. Medical Management Approach to Luminal CD over the past decade: Symptoms in CD correlate poorly with endoscopic activity ; More severe endoscopic activity predicts worse outcomes. Endoscopic healing is associated with improved short and long-term outcomes. Goals of therapy should include Endoscopic , as well as clinical remission. “Conventional” Sequential therapy - Steroids, followed by Immunomodulators, followed by Anti-TNF agents. Anti-TNF-α agents -- most effective in inducing and maintaining clinical remission, achieving endoscopic healing , and decreasing hospitalizations and surgeries in CD. Recent Advances - Therapy for CD is more effective in disease of shorter duration . Trend - using anti-TNF-α mAbs Earlier in course of CD.

54. Medical Management 5-ASA AGENTS Action : Inhibit LT production by inhibition of 5-LOX Activity. Inhibits Production of IL-1 and TNF. Limited role in Inducing Remission . Useful in Mild to Moderate CD . No clear role in Maintenance. Controlled-release preparation is also effective as maintenance therapy to prevent recurrence after a flare of disease has been effectively managed either medically or surgically . [Patients with Crohn’s disease avoid NSAIDs - powerful inhibitors of COX-1 and COX-2. NSAIDs may exacerbate Crohn’s disease]

55. Oral 5-ASA Preparations

56. Medical Management Antibiotics ( Ciprofloxacin/Metronidazole ) In Management of abscesses or wound infections. Maintenance therapy of chronic perineal septic complications.(with Anti TNF-Alpha) Bacterial overgrowth associated with chronic obstructive disease. Corticosteroids Most effective agents for controlling Acute Exacerbations Remission in active small bowel Crohn’s - Oral Prednisone - 0.25 and 0.5 mg/kg/d Or Methylprednisolone 40 to 60 mg given as a daily infusion.

57. Medical Management Immunomodulators (Azathioprine and 6-Mercaptopurine) Inhibit cytotoxic T-cell and NK cell function effective in treating Mild to Moderate Crohn’s disease REMISSION Azathioprine given at 2.0 to 2.5 mg/kg/d or 6-MP in doses of 1.0 to 1.5 mg/kg/d 50% to 60% response rate in patients with Active Crohn’s disease Biologic Therapies (Anti-TNF Therapies and Anti-Integrin Antibodies) Infliximab -80% response rate with a single dose of infliximab 5 mg/kg iv at weeks 0, 2, and 6, & then 5 mg/kg every 8 weeks thereafter Increased risk for infectious complications and intra-abdominal abscesses Natalizumab (anti-alpha-4 integrin) ; Vedolizumab (anti-α4-β7 ntegrin)

58. Shackelford's SURGERY of the ALIMENTARY TRACT 8th Ed

59. Shackelford's SURGERY of the ALIMENTARY TRACT 8th Ed The combination of a thiopurine and infliximab is the most effective inductive therapy Use Methotrexate for patients who do not tolerate thiopurine. American Gastroenterological Association (AGA) Risk Stratification for Assessment and Medical Therapy of CD

60. SURGICAL TREATMENT Goal : Provide Long-lasting Symptomatic Relief while avoiding Excessive Morbidity Complete extirpation of disease should NOT be the primary goal of surgery, as it does not produce cure and is frequently counterproductive. Main aims of Surgical Management: Treatment of Complications Palliation of Symptoms Avoiding Excessive Loss of Intestine OPTIMAL SURGICAL THERAPY : Leaving behind segments of intestine with Mild but Asymptomatic disease Resection of only the areas of Severe and Symptomatic Disease

61. Indications for surgical intervention in Crohn’s disease Acute onset of severe disease : Crohn’s colitis +/− Toxic megacolon (rare) Failure of medical therapy : Persistent symptoms despite long-term steroid use Recurrence of symptoms when high-dose steroids are tapered Drug-induced complications (Cushing’s disease, hypertension) Development of disease complications : Obstruction Perforation Complicated fistulas Hemorrhage Malignancy risk

62. Surgical Management Most common Indications : Intestinal Obstruction Abscesses and fistulas are frequently encountered during surgery Most abscesses : Amenable to Percutaneous drainage Fistulas: unless a/w symptoms or metabolic derangements, do not require surgical intervention C/o P resumed Appendicitis : I ntraop discovery of Inflammation limited to Terminal Ileum Can be caused by Acute Crohn's OR Acute Ileitis caused by Yersinia or Campylobacter Both conditions should be TREATED MEDICALLY; Ileal Resection NOT indicated Appendix, even if normal appearing, Should Be Removed - TO exclude from D/D

63. Surgical Management When the diagnosis of Crohn’s is known and Surgery is planned : Thorough examination of the Entire Intestine should be performed. Characteristics of Active Disease to be appreciated Intra Operatively : Thickening of the bowel wall Narrowing of the lumen Serosal inflammation and coverage by Creeping Fat Thickening of mesentery Skip lesions are present in approx 20% Cases Segmental Intestinal Resection of grossly evident disease followed by Primary Anastomosis is the usual procedure of choice

64. Surgical Management - Resection Margins & Technique of Anastomosis Microscopic evidence of CD at resection margins DOES NOT Compromise Safe Anastomosis In a RCT the effects of achieving 2-cm resection margins V/S 12-cm resection margins: NO evident differences with respect to Clinical Recurrence rates or Anastomotic Recurrences Recurrence rates similar whether margins - Histologically Free of OR Involved with CD Ideal Anastomotic technique after Intestinal Resection. - A RCT of 139 patients: Reconstructed using end-to-end sutured (2-0 PDS) anastomosis V/S Side-to-side Staples Anastomosis No differences in Endoscopic or Symptomatic disease Recurrence Alternative to Segmental resection for Obstructing lesions is Stricturoplasty

65. StricturoPlasty Planned for cases with Extensive disease and Fibrotic strictures Undergone Previous Resection At risk for developing Short Bowel Syndrome Depending on the length of the stricture < 12cm - Reconstruction Similar to Heinecke-Mickulicz pyloroplasty 12 - 25 cm - Similar to Finney pyloroplasty Mean lenghts 50 cm - Side-to-side Isoperistaltic enteroenterostomy Stricturoplasty is contraindicated in patients with intra-abdominal abscesses or intestinal fistulas . Bypass procedures (gastrojejunostomy) are also used in the presence of duodenal strictures, for which stricturoplasty and segmental resection can be technically difficult.

66. Fig: Heineke-Mikulicz strictureplasty Fig: Finney strictureplasty

67. Segment of intestine affected divided,2 limbs are drawn onto each other Longitudinal enterotomies are made along the Antimesenteric borders of the 2 limbs 2 limbs are anastomosed together in a lengthy side-to-side fashion. A C B

68. MANAGEMENT OF COMPLICATED CROHN’S DISEASE Crohn’s Disease of the Duodenum Almost always manifests with stricturing disease that can be managed by strictureplasty or with bypass procedures Distal segment (typically the terminal ileum or neoterminal ileum) that fistulizes into an otherwise normal duodenum Strictures : First 3 parts : Heinecke-Mikulicz strictureplasties Last Part : Finney strictureplasty If Duodenal stricture is lengthy or the tissues around the stricture are too rigid or unyielding , an Intestinal Bypass procedure should be undertaken

69. Intestinal Bypass for Stricture Duodenum M/C : simple Side-to-side Retrocolic Gastrojejunostomy Risk for Stomal ulcerations + : Highly Selective Vagotomy done Stricture limited to the third or fourth portions : Roux-en-Y duodenojejunostomy to the proximal duodenum Preferred

70. Duodenal Fistulas : Most duodenal fistulas located AWAY from the Pancreaticoduodenal margin , and thus, these fistulas can be managed by : Resection with Primary closure of the Duodenal Defect. Larger fistulas or fistulas that are involved with a large degree of inflammation: Roux-en-Y Duodenojejunostomy or with a Jejunal Serosal patch Duodenal resections are almost never necessary for Crohn’s disease, and they should be considered the surgical option of last resort.

71. COMPLETE INTESTINAL OBSTRUCTION Rarely requires urgent surgical intervention Vascular supply to the intestinal loop is never compromised. Almost all cases of Complete or High-grade Partial small bowel obstruction - respond to Conservative management Nasogastric Decompression, Intravenous hydration, and Steroid Therapy. - Rx High risk for Recurrent episodes and persistent symptoms. Elective surgery should be considered once episode of Complete obstruction has resolved If obstruction fails to respond to appropriate conservative treatment, surgery is required. High index of suspicion for Small Bowel Cancer as the cause of the obstruction needed

72. ILEOSIGMOID FISTULAS Asymptomatic ileosigmoid fistulas do usually require operative management. Large Ileosigmoid Fistulas can result in bypass of the intestinal contents from the terminal ileum to the distal colon and thus give rise to Debilitating Diarrhea . Rx : Simple division of Fistulous adhesion & Resection of the ileal disease . Defect in the Sigmoid colon is then debrided, and Simple closure is undertaken Sigmoid colon resection is necessary when primary closure of the fistula is at risk for poor healing .

73. ILEOVESICAL FISTULA 5% of Crohn’s disease patients Indicator of complex fistulizing disease, as most ileovesical fistulas occur along with other enteric fistulas. Can be managed medically for extended periods of time without significant complications Surgery is indicated when Recurring Urinary infections occur, Particularly Pyelonephritis , Concomitant potential for worsening of renal function Surgical treatment of ileovesical fistulas requires Resection of the Ileal disease with closure of the bladder defect Cystogram taken on postoperative day 5 - Only then Foley's to be Removed

74. ABSCESS Small intraloop or Intramesenteric Abscesses. Resection of the Defective segment and its Mesentery and Primary Anastomosis Large abscesses : best managed with CT-guided percutaneous drainage Enterocutaneous fistula often occurs : Spontaneously close or it may persist Such a fistula may spontaneously close or it may persist, and the intestine may continue to be a source of sepsis. Initial nonoperative management after successful percutaneous drainage can be undertaken in carefully selected patients If Drainage through the fistula continues, Surgical Resection of the Affected Segment of intestine becomes necessary.

75. Crohn’s Disease of the Colon CECAL DISEASE Terminal Ileitis - predominant component - With extension into Cecum Surgical Resection should encompass the Margins of Gross Disease Anastomosis b/w Neoterminal Ileum and the Proximal Ascending Colon Recurrence - Common at Anastamosis Site - At the Preanastomotic Ileum Risk for Recurrent disease within the Distal colon or the rectum is low. EXTENSIVE COLITIS WITH RECTAL SPARING Approximately 20% Cases of Crohn’s colitis. Total Abdominal Colectomy with Ileorectal Anastomosis . Upto 50% - Recurrence within Rectum- Require a Proctectomy with Permanent Ileostomy

76. Crohn’s Disease of the Colon PROCTOCOLITIS Total Proctocolectomy with Permanent Ileostomy Severe Perianal Disease - 2 staged procedure First stage - Resection of Colon and Majority of the Rectum with Short Rectal Stump created - Perineal Abscesses - drained and Fistulas are laid open Once the Perineal Sepsis is cleared & Perineum Healed - Short anorectal stump removed through perineal approach . Second stage - primary closure of the perineum - without the high risk of persistent perineal wounds . First step removes the diseased colon and rectum without creating a perineal wound that may be difficult to heal in the presence of active perineal sepsis

77. Perianal Disease Perianal Disease - Abscess, Fistulas, Fissures, Anal Stenosis, Hypertrophic Skin Tag. Originates from Inflammation within the Anal Crypts. Inflammation - Sepsis & Fistulization Usually A/w Active or Quiescent disease elsewhere within the GI tract Controversial : Disease activity parallels with Intestinal Disease . Surgical control of Intestinal Disease - Ameliorate - Perianal Manifestations Perianal Crohn’s disease tends to be Recurrent, Complex, and Progressive . Surgical Incision and Drainage - Incision closed to Anal Margin. Pack with Ribbon Gauze If Fistula Tract - Loose Seton . Low Lying Fistulas - Fistulotomy

78. Perianal Disease Since Introduction of Anti-TNF-α agents , Need for aggressive surgical intervention, such as Proctectomy, has significantly decreased . Level I evidence from two RCT using Anti-TNF-α agents demonstrated upto 50% 1-year fistula closure rate for CD with perianal fistulas . Drainage of any Undrained Infection and placement of Noncutting Seton drains - Symptomatic Relief Seton drain will : Preserve the Integrity of Anal Sphincter, Drain the fistula tracts. Limit the chances of abscess formation or perineal sepsis during medical therapy. Within 12 months - Rectum reexamined & if no luminal disease - complex fistulas - considered for repair. M/c Procedure - Endorectal Advancement Flap with healing rates ranging between 55% and 72%. *Emerging Alternative to Surgical Repair* - Injection of Allogenic or Native Stem Cells into Tract . - Mesenchymal stem cells ( MSCs ) & Gore Plugs - Success rate less than 50% in 1 yr

79. Photograph of a patient with multiple perianal fistulas secondary to Crohn’s disease An 18-year-old male Crohn's disease patient. A : A rubber band was placed during the surgery for drainage; B: Thirty weeks after the surgery

80. Perianal Disease Complex Fisutlas - Risk for Surgical Complications - higher. Aggressive Medical therapy is warranted Before Surgery Infliximab treatment - Healing of Complex Perianal Fistulas is seen in 60% of cases. Use of Setons with infliximab therapy - Improves overall effectiveness of Infliximab. Rectal Advancement Flap - Closure of the Internal Opening of the fistula Incision made at the Dentate Line ---> Flap of Mucosa and Muscularis Undermined. Advanced down Over the internal opening of the fistula & Sutured. Severe Disease - Fecal Diversion with a Stoma may be necessary. Proctectomy - Damage to Sphincters + Incontinence .

81. Conclusion Management of Crohn’s disease is complex and requires a Multidisciplinary Team Approach. Initial management is typically Medical and has had several advances. Surgical intervention is typically reserved for Refractory disease or complications of the disease . With Proper history, Utmost Clinical Suspicion and adequate Diagnostic confirmation, Crohn's Disease can be diagnosed early and treated appropriately.

82. ULCERATIVE COLITIS

83. Ulceratve Colitis Ulcerative colitis (UC) is a Chronic Relapsing and Remitting intestinal disorder plagued by diffuse and continuous mucosal inflammation involving the rectum, and extending proximally throughout the colon . Inflammatory hallmark in UC is limited to the mucosa . Infection with Salmonella or Campylobacter has been associated with an 8- to 10-fold Increased risk of developing of UC the following year . Patients who have undergone an Appendectomy are at decreased risk of developing UC.

84. Pathology (Contd) Mild Inflammation – Mucosa is erythematous and has granular surface. (Sandpaper appearance) Severe inflammation – Mucosa Hemorrhagic, Edematous and Ulcerated . Long standing disease – Pseudopolyps Pseudopolyps, Inflammatory polyps - Regeneration of Inflamed Mucosa Toxic megacolon –Transverse or right colon with diameter > 6cm with loss of haustrations in severe UC. Pseudopolyps in UC.

85. Pathology - Ulcerative COlitis Macroscopic Appearance Involves rectum and extends proximally to involve Entire Colon . 40 – 50 % - Disease Limited to Rectum and Rectosigmoid 30 – 40 % - Extends Beyond Sigmoid but not involving whole colon 20 % - Pancolitis No skip lesions. - Continous Involvement Backwash ileitis – Inflammation extends 2 – 3 cm into terminal ileum in 10 -20 %

86. Fig : Endoscopic image of a sigmoid colon afflicted with ulcerative colitis. Note the vascular pattern of the colon granularity and focal friability . Fig : Colonic pseudopolyps of a patient with intractable ulcerative colitis. Colectomy specimen

87. Microscopy Limited to Mucosa and Submucosa . Deeper layers may be affected in fulminant disease. Distortion of Crypt Architecture Basal plasma cells and lymphoid aggregates. Mucosal vascular congestion with edema and f ocal hemorrhage. Cryptitis and Crypt abscess – Neutrophils invade the epithelium in the crypts & expand Individual Crypts of Lieberkühn. Mucosal infiltration by Neutrophils, Lymphocytes, Plasma cells and Macrophages.

88. CrypT Abscess Fig : Active ulcerative colitis. The glands are irregular with branching, and focally, the long axis of the gland is horizontal rather than perpendicular. A central crypt abscess is present. There are increased numbers of chronic infl ammatory cells throughout the lamina propria

89. Fig: H&E stain of a colonic biopsy showing a Crypt abscess , a classic finding in ulcerative colitis Fig: Biopsy sample (H&E stain) that demonstrates marked lymphocytic infiltration (blue/purple) of the intestinal mucosa and architectural distortion of crypts.

90. CLINICAL FEATURES of UC Diarrhoea Tenesmus Passage of mucus Rectal bleeding Crampy abdominal pain Proctitis – Fresh blood and blood stained mucus , either with stool or streaked onto the surface of normal or hard stool. Sense of incomplete evacuation and urgency Proctosigmoiditis – May have constipation

91. Severe Colitis Grossly Bloody Diarrhea Anorexia Liquid stool containing Blood, Pus and fecal matter Nausea Vomiting SIGNS – Tender anal canal Blood on DRE Tenderness on palpation over colon in severe disease

92. Primary Sclerosing cholangitis Primary sclerosing cholangitis (PSC) occurs in 5% to 8% of patients with UC Patients with UC with HLA-B8 or HLA-DR3 --> 10 times more likely to develop PSC. PSC & Ulcerative Colitis typically have a more quiescent disease course. PSC + UC --> Risk of Colon Cancer 5 times > than with patients with UC alone. PSC Presentation : Asymptomatic - Diagnosed on AbN Laboratory Studies May present with Obstructive Jaundice + Abdominal Pain. PSC - Disease - progressive and ultimately fatal. Unless Liver Transplant done. Colectomy - No role / Effect in Course of PSC .

93. Ulcerative Colitis Clinical Presentation

94. Investigations Elevated acute phase reactants like CRP and elevated ESR Low Hemoglobin Leukocytosis may be seen Fecal lactoferrin and Fecal Calprotectin levels – Correlate with histologic inflammation and predict relapses Stool examination for bacteria, C. difficile toxin and ova and parasites. P-ANCA is positive in 60 -70 % . ASCA positive in 5 – 15 % . Anti-goblet cell antibodies (GAB) is +ve in UC

95. Imaging Diagnosis Computed Tomography , Ultrasound , MRI , and Endoscopy reveal Acute Mucosal Wall Thickening, Fat Stranding, Perforation Leukocyte scintigraphy is an uncommon imaging technique used to quantify leukocytes in the Intestinal wall Useful in Ascertaining the distribution (continuous vs discontinuous) of disease Response to Treatment Endoscopy remains the Gold Standard for imaging in Diagnosis of UC.

96. Fig: MRI. Yellow arrows point to segments of visualized colon which are narrowed , ahaustral , and foreshortened Fig: CT. Lead Pipe Appearance in both descending and ascending colon (yellow arrows) thick red arrow demonstrates post-inflammatory polyps

97. Fig: CT, Pancolitis . A. This cross-section demonstrates pancolitis with a striated wall appearance from mucosal enhancement andintramural edema (yellow arrows). B. Acute on chronic UC flare. Striated appearance is due to chronic submucosal fat deposition.

98. Fig: Toxic Megacolon. Abdominal plain radiograph, Grossly dilated transverse colon with “thumbprinting” due to mucosal edema Fig: Stricture in Chronic Ulcerative Colitis.

99. SIGMOIDOSCOPY and COLONOSCOPY With biopsy – to assess disease activity and confirm diagnosis Sampling of the ileum, four colonic sites, and the rectum , with a minimum of two biopsies from each site Mild disease – Mild erythema and friability with mucosal inflammation Severe disease – U lcerations & Spontaneous bleeding starting at Rectum with proximal extension In addition, there is often loss of vascularity , loss of haustral folds , mucosal erosions , mucosal friability, and evidence of mucopurulent exudates. Longstanding disease - Pseudopolyps are often observed

100. Figure : An endoscopic view of ulcerative colitis. A. Mild ulcerative colitis. B. Moderate ulcerative colitis. C. Severe ulcerative colitis. The mucosa is plagued with white exudative granularities

101. COMPLICATIONS Only 15% present with catastrophic illness Massive bleeding → 1% patients, if > 6-8 units of blood needed within 24-48 hrs., colectomy indicated Toxic Megacolon → If diameter > 6 cm, seen in 5%, triggered by electrolyte abnormalities & narcotics Perforation → most dangerous complication, symptoms may be masked by glucocorticoids Strictures occur in 5-10% patients, if impassable with colonoscope,must be assumed malignant until proven otherwise.

102. Colonic Stricture Occur in 5% to 12% of patients with Chronic Ulcerative Colitis Most often Benign and caused by hypertrophy of the muscularis Cancer Must be Excluded in All Colonic Strictures of UC Colonic stricture in a patient with ulcerative colitis must be presumed carcinoma until proved otherwise. - Sabiston Textbook of Surgery 18th Edition If malignancy cannot be ruled out by Endoscopy, the Presence of a stricture is an Indication for operative intervention. - Sabiston Textbook of Surgery 18th Edition Three important features are suggestive of Malignant Strictures : Appearance Later in course of UC ( 60% after 20 yrs v/s 0% before 10 yrs ) Location Proximal to the Splenic Flexure (86% malignant) Large Bowel Obstruction caused by the Stricture .

103. Risk for Carcinoma Risk Factors : Prolonged duration of disease, Pancolonic disease, Continuously Active disease, & Severity of the Inflammation . Cumulative Risk for cancer : 25% at 25 yrs; 35% at 30 yrs; 45% at 35 yrs ; 65% at 40 yrs Involvement of Left side of the colon - Lower risk < Entire Colon - High Risk Surveillance Colonoscopy : Every 1 to 2 years beginning 8 years after the onset of Pancolitis. 12 to 15 years after the onset of Left-Sided Colitis. At least 30 Random Biopsy S pecimens obtained. ( Traditionally - 10 ) Risk of Ca with degree of dysplasia 10% of colons displaying low grade dysplasia, 30% to 40% with high-grade dysplasia, More than 50% of colons - Dysplasia Associated with Lesion or Mass ( DALM )

104. Toxic Megacolon Serious, Life-threatening condition Can occur in Ulcerative colitis , Crohn’s colitis , and Infectious Colitides - Pseudomembranous Colitis . Bacterial Infiltration of walls of the colon ---> creates a Dilation of Colon ---> Progresses to Point of Imminent Perforation Necrotic, Thin-walled bowel in which Pneumatosis can often be seen radiographically. Medical Therapy - Some cases Reported - High Rate of Recurrance with Subsequent Surgery Aggressive Preoperative Stabilization Volume Resuscitation with Crystalloid solutions to prevent Dehydration 2 o to 3rd Space Fluid Loss. Stress Dose Steroids for patients previously on Steroid therapy. Broad-Spectrum Antibiotics. Surgical : Mainstay in Toxic Megacolon. Total Abdominal Colectomy with Ileostomy and Preservation of the Rectum for Anastamosis at a later date

105. Shackelford's SURGERY of the ALIMENTARY TRACT 8th Ed

106. Shackelford's SURGERY of the ALIMENTARY TRACT 8th Ed

107. MEDICAL MANAGEMENT No medication cures ulcerative colitis, many can reduce symptoms. The goals of medication therapy are: Inducing and Maintaining Remission . Improving the person's quality of life. 5-ASA Agents Induces & maintains clinical remission in mild to moderate UC Patient usually improves symptoms by 2 to 4 weeks

108. Glucocorticoids Prednisone (oral) started at 40 – 60 mg/ day for active UC unresponsive to 5-ASA therapy Parenteral → Hydrocortisone 300 mg / day (or) Methylprednisolone 40 – 60 mg / day New → Budesonide → released entirely in colon, no side-effects,dose = 9 mg / day for 8 weeks, no taper required Topical route may be used for distal colitis & rectal involvement

109. TNF INHIBITORS Infliximab, adalilumab, and golilumab are effective in inducing and maintaining clinical remission in UC Infliximab - intravenously every 8 weeks after induction dosing. Adalilumab and golilumab - subcutaneous injection every 2 weeks Can exacerbate Latent Tuberculosis or Hepatitis B , leading to Disseminated TB or Fulminant Hepatitis B . Should be evaluated for these infections Prior to therapy

110. Management of Acute Colitis Severe Acute Colitis presents a potential surgical emergency. Acute colitis may be initially treated with Medical Therapy and daily re-evaluation Deterioration or failure of symptoms to resolve within the first 3 days triggers the need for urgent colectomy . The Main Goals of operative intervention include Achieving Definitive Cure by Resection of the Colon and Rectum, Reconstructing a Route of Elimination Minimizing morbidity and improving quality of life.

111. Indications for Surgery Fulminating disease Chronic disease with anemia, frequent stools,urgency & tenesmus Steriod dependant disease Massive Colonic Bleeding Risk of Neoplastic change Dysplasia - Carcinoma Colonic Stricture - Malignancy cannot be ruled out in Endoscopy Extraintestinal manifestations

112. Surgical Management Removal of the entire colon "cures" Ulcerative colitis. Eliminates the long-term risk of cancer . A surgeon can do that by two different types of surgery : Proctocolectomy and ileostomy. Proctocolectomy and ileoanal reservoir.(IPAA) Full recovery from both operations may take 4 to 6 weeks. Surgery of choice in urgent and emergent situations is Total Abdominal Colectomy (TAC) with end ileostomy . - Later - Completion Proctectomy + IPAA Rectal stump - Hartmann pouch /closure with exteriorization into S/C tissue.

113. Total Colectomy with Ileorectal Anastomosis Following standard colectomy, Rectum - left intact ; obviating deep pelvic dissection and potential injury to pelvic nerves. Rectal Remnant - Requires continued Medical therapy and Surveillance, - Chance Of Recurrance Risks of colitis and Later Cancer have not been eliminated. Anastomosis is at the level of the Sacral promontory , where the Superior Hemorrhoidal vessels are left intact. Usually not Followed. Except in Patients with Significant debility who are poor operative candidates.

114. Total Proctocolectomy with Ileal Pouch-Anal Anastomosis Terminal ileum - Reconstructed to recreate a fecal reservoir in order to mimic anorectal continence after colectomy. Single or Staged Procedure. Many variations to the Ileal Pouch - S, J, and W Adequate length of the Ileocolic Pedicle must be confirmed. Distal ileum is used to construct the J-pouch. Inflow and outflow limb - anastomosed together using a linear stapler. Apex of the Pouch is then anastomosed to the Rectal cuff.

115. Reconstructive Proctocolectomy with ileoanal Pouch

116. Surgical Options in Surgical management of UC One-stage Total Proctocolectomy with ileal pouch–anal anastomosis ( IPAA ); Two-stage approach - Total Proctocolectomy with IPAA + diverting Loop Ileostomy , - Followed by Closure of Ileostomy Modified Two-stage procedure - Total Abdominal Colectomy( TAC ) + End Ileostomy - Completion proctectomy with IPAA (without ostomy) Three-stage - Total Abdominal Colectomy ( TAC) + End Ileostomy - Completion Proctectomy + IPAA - Reversal of Ileostomy Modified 2 stage approach - Safe alternative to traditional two- & three-stage approaches Decreases the risk for an anastomotic complication - Lower Risk of Anastamotic Leak Without increasing the cost or the number of surgeries the patient has to undergo.

117. Elective Operations for Ulcerative Colitis

118. Kock Pouch (Continent Ileostomy) High-Volume , Low-Pressure Single Chambered Reservoir Made by Suturing several limbs of Ileum together after the antimesenteric border has been divided. Outflow tract : Maintained by an Intussuscepted Nipple Valve Design of the pouch was Permit Fecal material to Accumulate Emptied at the Patient’s Convenience Several times a day. Inserting a tube at the Level of Stoma into the Reservoir to Release its Contents. Indication : Surgical rescue option following failed IPAA Major complications include Valve Dysfunction , the most common of which is valve de-intussusception

119. POSTOPERATIVE COMPLICATIONS Septic Complications Anastomotic Leak Abscess Fistulas Non-Septic Sequelae Intestinal Obstruction Stricture Cuffitis Pouchitis

120. Pouchitis M/C complication following restorative proctocolectomy - 16% to 48%. More common in UC with primary sclerosing cholangitis . Other extraintestinal manifestations a/w 10-fold increase in risk after 5 yrs follow up. Mediated by Same Proinflammatory process underlying the Primary diagnosis. Symptoms : Increase in Fecal Frequency Bowel consistency is Looser Secondary to Exudative Inflammation with Blood staining or Mucus . Villous Atrophy and Crypt Hyperplasia are classified as Colonic Metaplasia - Response to Inflammation.

121. Treatment Oral metronidazole at a dose of 750 to 1500 mg/day for 7 to 14 days Not responding to Metronidazole : cyclic courses of three or four antibiotics, such as ciprofloxacin, amoxicillin/ clavulanic acid, erythromycin, and tetracycline, given at weekly intervals Budesonide suppositories (1.5 mg/day)

122. CONCLUSION Patients with Ulcerative Colitis - Need High Suspicion of clinician and early diagnosis. Patients have Good improvement in symptoms and can be presented with a multitude of Options when considering surgery. Emergency situations and othe important indications for surgery must be considered. Ulcerative Colitis - Surgery can Offer 'Cure' . But need appropriate medical and post operative care.

123. DISTINGUISHING CHARECTERISTIC FEATURES b/w ULCERATIVE COLITIS & CROHN'S DISEASE

124. Conclusion Uncontrolled Immune Mediated Inflammatory response in Genetically predisposed individuals to a still Unknown Environmental Trigger that interacts with the Intestinal flora. Enormous amount of information emanating from epidemiological studies providing expanded insight into occurrence, distribution, determinants, and mechanisms of IBD. Evaluation, diagnosis, and monitoring of inflammatory bowel disease (IBD) has improved significantly over the past few decades Evolution of serologic markers has improved our understanding of the pathogenesis and natural history of IBD. Advancements in endoscopy and endoscopic scoring systems have improved the accuracy of diagnosis and the efficacy of surveillance of IBD patients.

125. References Maingot's Abdominal Operations 13th Edition Schwartz Principles of Surgery 11th Edition Sabiston Textbook Of Surgery 18th Edition Shackelford's Surgery of the Alimentary Tract 8th Edition Bailey & Love Textbook of Surgery 27th Edition Harrison's Principles of Internal Medicine 20th Edition Gastroenterology Clinics of North America Volume 33 , Issue 2 Russel D.Cohen - Inflammatory Bowel Disease