Talk given by Mr John Abercrombie, Consultant Colorectal Surgeon, Queen's Medical Centre, Nottingham, at the Dukes' Club AGM 2011

1. CROHN’S DISEASE OF THE ANUS

2. Although most patients will still, eventually, have surgery, the care of CD is now primarily in the hands of medical gastroenterologists ..... Surgery may then be consigned to the treatment of last resort. It must be recognised that this carries implicit risk, because those patients who come to surgery will have more complicated disease and are likely to be at higher risk of septic complications. ECCO guidelines

5. Surgeons like to cut .. Difficult to get hold of

8. NATURAL HISTORY CLASSIFICATION / SEVERITY ASSESSMENT MANAGEMENT MEDICAL SURGICAL

9. INCIDENCE 3.8 – 80% ISOLATED / DISEASE ELSEWHERE SPECTRUM MINOR ANAL AILMENTS SEVERE DISEASE Nb. Differential diagnosis TB, STD, Neoplasia, Hidradenitis GENETICS MALIGNANCY

10. “ faecal incontinence is the result of aggressive surgeons and not of progressive disease.” Alexander-Williams Dis Colon Rectum 1976 19; 518-519

11. TREATMENT IS BEST CONSIDERED PALLIATIVE SYMPTOM CONTROL SYMPTOMS ARE OFTEN SURPRISINGLY WELL TOLERATED “ THE PATIENT IS THE ONE WITH THE DISEASE” Shem The House of God

12. Perianal lesions in a series of patients a follow up clinic 110/202 (54%) Skin tag 75 Fissure 38 Low anal fistula 40 High anal fistula 12 Rectovaginal fistula 6 Ishiorectal abscess 32 Intersphincteric abscess 8 Perianal abscess 7 Supralevator abscess 6 Anorectal stricture 19 Haemorrhoids 15 Anal ulcer 12 Keighley and Allan Int J Colorectal Dis 1986

13. Hughes 1979 Ulceration Fistula/Abscess Stricture

14. Hughes 1979 Ulceration Fistula/Abscess Stricture Hughes 1992 Associated anal Proximal Disease Conditions intestinal activity disease U F S A P D

15. Perianal Crohn’s Disease Activity Index Discharge 0 – 4 Pain / Restriction of activities 0 – 4 Restriction of sexual activity 0 – 4 Type of perianal disease 0 – 4 Degree of induration 0 – 4 Irvine J Clin Gastroenterol 1995 20; 27-32

16. SIMPLE PRACTICAL CLASSIFICATION SYMPTOMS SYMPTOMS SYMPTOMS SYMPTOMS RECTUM NORMAL SIMPLE ANAL PROBLEM COMPLEX ANAL PROBLEM RECTUM DISEASED

17. THE ACUTE ANUS IN CROHN’S DISEASE SURGICAL EMERGENCY REQUIRES EFFECTIVE DRAINAGE (Antibiotics) PROBLEMS OF SPECIALISATION (INVESTIGATIONS)

18. ASSESSMENT OF THE NON-ACUTE CROHN’S BOTTOM EXAMINATION OF THE RECTUM (rest of the gut) ENDOANAL ULTRASOUND MRI RECTAL EXAMINATION UNDER ANAESTHETIC

19. NORMAL RECTUM: SIMPLE ANAL PROBLEM Tags / fibroepithelial polyps Anal fissures Haemorrhoids Low anal fistula Fistulotomy 8% - 100% May be treated surgically if the symptoms justify the intervention

20. 61 patients undergoing surgical treatment for fistula 13 – 140 months follow up 24 Seton 28 fistulotomy 9 advancement flap 5/28 low (simple) fistula recurred Koperen et al Br J Surg 2009; June 96; 675-9

21. NORMAL RECTUM: COMPLEX ANAL DISEASE Multiple pathologies ie tags and fistulae Stricture Dilatation Transsphinteric fistula Seton Lay open Horseshoe / multiple fistulae Complex fistula surgery “ Rectovaginal” fistulae Series report healing rates of 20 – 100% Koperen 5/9 recurred Little appetite for heroic perineal surgery in the UK - Loose seton sepsis control

22. DISEASED RECTUM Role of surgery limited to ensuring effective drainage of pus to allow maximal medical therapy Sepsis control / loose seton

23. SALICYLATES STEROIDS METRONIDAZOLE Long course CIPROFLOXACIN 50% healing rate Toxicity Recurrence

24. IMMUNE SUPPRESSION AZATHIOPRINE (6M-P) Extensively used first line treatment Slow … 3 – 4 months to heal 30 - 50% Risk of myelosuppression Need monitoring CICLOSPORIN MYCOPHENELATE TACROLIMUS

25. INFLIXIMAB Anti TNF alpha antibody Placebo controlled trial Fistula closure 26% placebo 68% infliximab All fistulae closed at 4 weeks 13% placebo 55% infliximab Median duration of closure 3 months Present et al NEJM 1999 3340:1398-1405

26. 306 patients 3 doses 5 mg/kg at 0, 2 and 6 weeks Responders (195) randomised at week 14 Placebo Infliximab End point .. Time to loss of response Median loss of response 14 weeks placebo >40 weeks infliximab At 54 weeks 19% of placebo, 39% infliximab fistula free Sands 2002 ACCENT 2 trial

27. 26 patients 18 complex fistula 8 rectovaginal fistula Combination of seton + immune suppression (80% infliximab) FU 4.9 +/- 9.6 years CDAI + imaging to assess response Seton removed after 2-3 rd dose Initial response 44% for complex disease 62 % for simple Relapse rate very unclear, Rectal involvement poor results Tougeron et al Dig Dis Sci. 2009 Aug;54(8):1746-52.

28. Adverse events Perianal abscess Infusion reaction Delayed hypersensitivity Drug induced lupus Serious infections TB Pneumonia Sepsis Cyptosoporidiosis Listeriosis Pneumocystis Aspergillosis Neoplasia

29. NICE 2002 Patient has severe active Crohn’s disease Treatment with other immunomodulators / steroids has not worked or there has been intolerable toxicity Surgery is inappropriate Expected review July 2008 (issued 2010) Cerolizumab pegol Adalimumab

30. OTHER THINGS THAT HAVE BEEN TRIED Fibrin glue Fistula plugs (80%) Direct injection of infliximab into fistulous tracts Granulocyte colony stimulating factor Thalidomide Hyperbaric oxygen

31. 10 year follow up of 109 patients 10 required rectal excision (5 for anal disease) No other patient developed incontinence Buchanan et al Am J Surg 1980 140(5) 642-4 30/97 patients required a stoma Mueller et al J Gastointest Surg 2007 11;529-37

32. DEFUNCTIONING PROCTECTOMY

33. Perianal crohn’s disease and pregnancy Caeser or not? Malignancy (SCC Frisch 2000 Fistula cancer)

37. SUMMARY RECTUM NORMAL SIMPLE ANAL PROBLEM COMPLEX ANAL PROBLEM RECTUM DISEASED

38. MANAGEMENT PLAN EMERGENCY TREATMENT DRAINAGE STABILISATION SETON OPTIMISE MEDICAL Rx ATTEMPT HEALING SURGERY INFLIXIMAB / REMICADE PROCTECTOMY Assoc Coloproct Postion Statement on Anal fistula Williams et al Colorectal disease Oct 2007

39. CONCLUSION Life long illness Management is approached with the palliative philosophy of symptom control Many patients do avoid proctectomy

40. POUCHITIS DEFINITION PATHOGENESIS TREATMENT

41. POUCH OUTCOMES DOING WELL DOING BADLY “POUCHITIS” ↑ frequency Bloating Urgency Pain Blood Sepsis incontinence

42. Long rectal stump Small capacity pouch Stenosis Poor sphincter function Cuffitis Crohn’s disease NSAID enteritis Infections CMV, C Diff “ Irritable pouch syndrome”

43. DEFINITION Clinical picture Endoscopic appearance Histological appearance (Pre-pouch ileitis)

44. Objective pouchitis score Pouchitis activity score Pouchitis Disease Activity Index Clinical symptoms 0-6 Endoscopic appearance 0-6 Pathology 0-6 Score ≥7 = Pouchitis Sensitivity 60% Specificity 96%

45. Incidence 25 – 50% at 10 year (FAP 3 – 14%) 5 – 20% relapsing pouchitis 1% of patients lose their pouch

46. Pathogenesis Risk factors UC Cholangitis Other non GI manifestations Extent of disease ? Smoking acute / chronic

47. Dysbiosis ? Sulphate-reducing bacteria ? Anaerobe ? Clostridium ? Candida terminal-restriction fragment length polymorphism (T-RFLP) profiling Proteomics Faecal stasis Mucosal ischaemia Autoimmune Metaplasia and then recurrence of UC?

48. TREATMENT ANTIBIOTICS Metronidazole 750 – 1500 mg/day Ciprofloxacin 500 mg 80 – 90% response rate in small RCTs /open label studies Augmentin, Erythromycin, Tetracycline Rifaxamin

49. Probiotics Treatment 23 patients treated with 2 sachets VSL 3 /day for 4 weeks 70% achieved remission and were maintained Gionchetti et al Dis Colon Rectum. 2007 Dec;50(12):2075-82

50. Gionchetti et al. Gastroenterology 2000;119:305-309 Maintenance of remission Log 10 CFU/g dry weight

51. ANTIBIOTIC RESISTANT DISEASE Antibiotic combination Budesonide Systemic steroid Activated Carbon Microspheres SCFA enema / suppository Glutamine Mesalazine Bismuth carbomer enema Infliximab Adalimumab

52. Combination therapy Targeted Therapy 15 patients 13 relapsed after combination 2 after ciprofloxacin Coliform culture showed cipro resistance in all + varied other patterns of resistance 80% remission with tailored 4 week antibiotic Maintained with rotating regime Mclaughlin et al 2009

53. Infliximab Calabrese et al Aliment Pharmacol Ther. 2008 May;27(9):759-64. 10 patients with chronic pouchitis All had proximal lesions on capsule endoscopy Infliximab 5 mg/kg at 0, 2 and 6 weeks 9/10 “clinical remission”

54. SUMMARY Pouchitis is common(ish) It is poorly defined (pouches behaving badly) Its pathogenesis is obscure Antibiotic treatment is reasonably well established as first line therapy Antibiotic resistant pouchitis is a miserable problem and there are a variety of potential treatments available

55. ABSOLUTE INDICATIONS Toxic dilatation www.survivingsepsis.org Perforation Torrential bleeding

57. Travis et al … BSG Guidelines 2004 Severe UC should be managed jointly by a Gastroenterologist in conjunction with a colorectal Surgeon Patients should be kept informed of treatment and prognosis, including a 25 – 30% chance of needing colectomy

58. Objective re-evaluation on the third day of intensive treatment. A stool frequency of >8/day or CRP>45 mg/L at 3 days appears to predict the need for surgery in 85% of cases. Surgical review … is appropriate at this stage. (Grade B) Consideration of colectomy or iv ciclosporin if there is no improvement during the first 3 days (Grade A)

59. 30 yr old female Previously treated for proctitis ( 3 years) 2 week history of bloody diarrhoea x 20/24 hrs 40 mg Pred for 8 days prior to admission Couldn’t hold pentasa supps CRP = 77 on admission DAY 5 C Diff neg Abdo tender BO x 19 CRP 63 PLAN ? Aza ? Involve surgs Start cyclo

60. ABDOMINAL PAIN IN COLITIS Very little in the books Prognostic significance unknown Difficult to assess Voluntary guarding Rebound PCA

61. Day 6 Starting Cyclo R/V surgs Day 7 Surg Reg “ Severe UC perhaps beginning to get better ? Get the colorectal Surgeons” CRP 93 BO 15 (Previously 19)

62. Day 8 s/b cons Still profuse diarrhoea + no improvement Day 10 BO 15 begin polymeric diet Day 11 BO 5 … better Day 12 BO 14 .. Sb Cons Refer to CR surgs Pt desperate to avoid surgery want 2 nd opinion from another gastroenterologist Surgery recommended (infliximab considered) Day 13 Transfer to CR Day 14 Subtotal colectomy

63. ISSUES Guidelines .. Not adhered to. Slow to start ciclosporin Slow to refer to surgeon (wishful thinking on the part of the Gen Surg reg) (straw grasping) Surgery not explored with patient until late in the illness

64. 23 year old male 2 previous admissions in 3 months prior to attendance Admitted 2 weeks after previous discharge Not better as an OP BO 12-13 Abdo pain in both iliac fossae CRP 16 iv steroids + polymeric diet Day 2 C Diff + ve Metronidazole started

65. Day 4 flexi sig “Horrid colitis” BO x 14 CRP 22 Day 6 S/B colorectal surg Can consider cyclosporine Day 7 Mother lives in Cyprus Day 10 ESR 43 Alb 25 BO x 18 Day 11 L sided abdo tenderness BO x 20 CRP 17 Day 12 Transferred to surgery

66. 49 acute colectomy patients Half felt that surgery wished they had earlier surgery 10% felt surgery was too soon 40% Didn’t feel strongly or didn’t like to say Fitzgerald E et al 2008

67. “ Only had the operation at my request” “ Knowing what I know now I would have had the operation much earlier” “ Not told about possible surgery. Would have had it straight away” “ I wanted to try everything before op” “ I was slightly dubious about surgery but should have had it when diagnosed” “ Would have preferred not to have to try all the medicines “ Get rid of it or you’ll be dead”

68. SHORTCOMINGS IN THE CARE PHYSICIAN SURGEON PATIENT AND FAMILY SYSTEMATIC PROBLEMS WITH THE GUIDELINES

69. INDICATIONS FOR SURGERY FAILURE OF PHYSICIANS TO CONTROL THE DISEASE ACUTELY CHRONICALLY SYMPTOMATICALLY NEOPLASTICALLY FAILURE FAILURE FAILURE FAILURE FAILURE FAILURE

70. INDICATIONS FOR SURGERY DISEASE THAT IS DRUG RESISTANT ACUTELY CHRONICALLY SYMPTOMATICALLY NEOPLASTICALLY BAD DISEASE BAD DISEASE BAD DISEASE BAD DISEASE MOST DEFINITELY NOT FAILING PHYSICIANS

71. SURGEON RELATED PROBLEMS 70 % of patients don’t need one Availability Straw clutching Like to cut? Fallibility

72. PATENT RELATED PROBLEMS Loss of control Dread of stoma Feeling rotten Family flying back from abroad

73. INSTITUTIONAL / ADMINISTRATIVE Management in series (should be parallel) Lack of urgency .. Days slipping away Specialism Difficulty getting to theatre

74. PROBLEMS WITH THE GUIDELINES Guideline: a line drawn, or a rope, etc fixed to act as a guide; an indication of a course that should be followed, or of what future policy will be. The Chambers Dictionary 1998 edition p 715

75. Rules for the management of …..

76. AT ADMISSION Start treatment Spell out the plan Describe the place of surgery Stoma / IBD nurse Severe or unusual pain .. Call a surgeon AT DAY 3 If targets not met (Stool >8 or CRP>45) A surgeon should be involved If 2 nd line drug treatment is to be used then redefine targets and time limit them (including when the surgeon should come back)

77. WHEN THE PATIENT IS BETTER Is he/she likely to relapse? Consider calling the surgeon now that you have achieved remission Elective surgery is better than emergency

78. CONCLUSION BSG rules should be observed (stool frequency + CRP) Introduce the concept of second line therapy (incl surgery) for bad disease on day 1 Set measurable targets and time constrain them

79. FERTILITY, PREGNANCY AND THE ILEO-ANAL POUCH

80. SEXUAL FUNCTION AFTER POUCH MALE FEMALE Evidence is conflicting

81. Studies often questionnaire based Response / participation rates 40 – 50% Based on Female sexual function index 73% preop dysfunction 21% post op Davies et al Dis Colon Rectum 2008 47% postop Ogilvie JW Br J Surg 2008 8% preop 15 % post op Meta-analysis Cornish JA et al Dis Colon Rectum 2007

82. INFERTILITY Inability to conceive after 12 months of trying (unprotected intercourse) FECUNDITY Ability to conceive

83. INFERTILITY Olsen 1999 237 women 15 years prior to surgery 251/286 From disease onset to surgery 120/131 Within 12 months of stoma closure 34/69

84. Olsen 2003

86. Several studies 1.5 – 3 x increase in infertility rate

87. DELIVERY Normal delivery Risk of sphincter injury 30% on US 10% incidence of incontinence (2% severe) Pudendal nerve injury

88. Higher elective caesarian rate BUT Extensive evidence showing that vaginal delivery +- episiotomy does not result in altered pouch function

89. SUMMARY Sexual dysfunction in women is common after ileo-anal pouch surgery Infertility rates are much higher after ileoanal pouch surgery Vaginal delivery (selected cases) is safe (probably)