Inflammatory bowel disease
Dr Van de putte D
Prof Dr P Pattyn
Ghent, 18/12/2018 Colitis Ulcerosa
Thomas Sydenham (17e eeuw) Non contagious “bloody flux”
Samuel Wilks (19e eeuw) “Simple ulcerative colitis”
Lockhart Mummery (1905), St. Mark’s Hospital “Electric sigmoidoscope” “Irrigation of the inflamed mucosa might heal the colonic mucosa” Colitis Ulcerosa
Brown “Ileostomy to rest the bowel” (protruding ileostomy through the incision)
Strauss Koenig Rutzen bag (1945) “Rubber bag cemented to the skin”
Dennis (1945) “Colectomy and ileostomy”
Brooke (1951)( Birmingham) and Turnbull (Cleveland) Colitis Ulcerosa
Parks and Nichols (1978): Modern ileal pouch operation Crohn
Burrill Bernard Crohn (1884-1983) Alfred Berg Leon Ginzburg Gordon Oppenheimer 1949 bypass operations , extended surgical resection of histological disease (short bowel) 1932 “regional ileitis” “growing realization of the increasing incidence of recurrences following all types of surgical interference” Eisenhower: 1956 bypass JFK: 1937: Mayo clinic: ‘colitis’ voor ileitis Indeterminate colitis
A definitive histopathological diagnosis of UC or Crohn’s is not always possible following colectomy
10%-15% of surgical specimens diagnosis of indeterminate colitis Incidentie van IBD ?
neemt toe ?
neemt af ?
blijft stabiel ? ↑ incidence in time and in previous low incidence regions, eg Asia –Eastern europe
Molodecky et al. Increasing incidence and prevalence of inflammatory bowel diseases with time, Systematic review, Gastroenerology 2012 Invloed van geografie , demografie en tijd: IBD diagnose is duidelijk toegenomen over de laatste 4 decades
Betere diagnostiek ? en/of meer blootstelling aan een ongedefinieerde trigger ?
Geen verband tussen toename en in gebruik nemen van nieuwe beeldvormingstechnieken Incidentie van IBD
- Risk for general population: 0,1%
- Approximately 10% of patients has positive family history
- Risk if 1 parent has IBD: CD: 2-3%, UC:0,5-1%
- Risk if 2 parents have IBD: >30 % at 28 years of age
- 20-50 fold increase in prevalence among siblings Etiopathogenesis
Genetic factors Intraluminal antigens Environmental factors
- Racial and ethnic differences - Increased incidence among monozygotic twins (CD) - Association with certain genetic syndromes
DYSRGEGULATED IMMUNE RESPONSE GENETIC FACTORS ENVIRONMENTAL FACTORS
Rookstop bij crohn: - Minder opstoten - Minder immunosuppressie nood
Ponder et al. A clinical review of recent findings in the epidiology of inflammatory bowel disease, Clin Epidemiol 2013; 5:237-247
Anatomic distribution and behaviour of IBD CU
Western Eastern Europe
Silverberg et al. Can J Gastroenterol 2005; Burisch et al. Gut 2013 TYPES OF CROHN CROHN
Silverberg et al. Can J Gastroenterol 2005 Risk for complicated disease course: L4>L1>L3>L2 LONG TERM EVOLUTION OF CROHN S DISEASE BEHAVIOUR
Cosnes J et al. Inflamm Bowel Dis 2002
CROHN
20-30 % at first presentation Lehmann score
Pariente et al. PEDICTORS OF POOR PROGNOSIS IN CU CHANGE IN MORTALITY in 21 COUNTRIES FROM 1951-2005 - Young age - Extensive disease - No appendectomy in childhood - Non smoking
PREDICTORS OF POOR PROGNOSIS IN CD - Young age - Perianal disease - Need for steroids - Smoking - Extensive disease - Deep ulcers
Sonnenberg, Int J Epidemiol 2007 RISK FOR CRC IN CU by decade
Overall cancer incidence 3,7% and 5,4% in pancolitis rises with duration of disease:
Castano-Milla et al. 2014 Cumulative probabilities of 2% by 10 years, 8% by 20 years and 18 % by 30 years
Eaden et al. Gut 2001 Sureillance endoscopy
Normally start 8 years after initial diagnosis, except PSC Symptoms UC Symptoms CD
- Dependant on disease extent, location, severity, behaviour and complication - Dependant on disease extent and severity of inflammation - Onset subtle and atypical - Onset usually slow and insidious - May manifest acutely: severe pain, - Severe attack with systemic symptoms (tachycardia, fever, obstruction, hemorrhage weight loss) - More heterogeneous manifestation than UC - Rectal bleeding (up to 90%) - Abdominal pain (84%) - Diarrhea (up to 83%) - Diarrhea (57%) - Rectal urgency (up to 85%) - Weight loss (43%) - Nocturnal defecation - Blood/mucus in the stool (up to 50%) - Tenesmen - Systemic symptoms (fever) - Crampy abdominal pain - Anemia - Passage of mucopurulent exudates - Failure to grow - Anorexie, weight loss, fever, nausea, vomiting - Bowel obstruction - Extraintestinal manifestations - Nausea, vomiting, abdominal distention → disease activity: Truelove and Witts score - Symptoms of perianal/RV/enterocutaneaous/entero- enteric fistulae or abcesses Diagnosis
ENDOSCOPY
Ileal involvement
Skip lesions
Lee et al. Clinical Endoscopy 2016 Diagnosis
ENDOSCOPY UC ENDOSCOPY CD
Simple endoscopy scores Crohn disease
vs Crohn’s endoscopic index of severity Diagnosis
HISTOLOGY UC HISTOLOGY CD
- Only mucosal layer involved - Transmural inflammation - Epithelial erosions - Mixed infiltrate - Crypt distortion - Discontinuous inflammation - Crypt abcesesses - Granuloma’s - Globlet cell deletion Extra-intestinal manifestations IBD
- Musculoskeletal (peripheral and axial arthropathy, osteoporosis)
- Cutaneous (pyoderma gangrenosum, erythema nodosum)
- Ocular (episcleritis, uveitis)
- Hepatobiliary (primary sclerosing cholangitis)
- Thromboembolism
- Anemia THERAPY
1998 1998 1998 Introductie van Infliximab
Monoclonaal Al ↔ TNF alfa
THERAPY IBD: Step up strategy
Combi IFX +thiopurine is superior in CD and UC
ANTI-TNF: Infliximab (Remicade) (UC-CD) – Adalimumab (Humira) – Golimumab (Simponi) (RA) VEDOLIZUMAB (Entyvio) (UC-CD) USTIKINUMAB (Stellara) Azathioprine (Imuran) of Mercaptopurine (Purinethol) – Thioguanine (Lanvis) (THIOPURINES ) Methylprednisolone (Medrol) bij matige tot ernstige CU en Crohn (ileo)colitis
Blokkeert pro-inflammtoire genen + promoot anti- Lokaal: Budesonide (Entocort-Budenofalk lokaal bij proctitis) of inflammatoire genen per os bij milde of matige ileitis– of beclomethasone diproprionaat po (Clipper) bij links CU niet responsief op 5ASA
Anti-inflammatoir en anti- Indicatie : milde CU: Mesalazine (Pentasa- Colitofalk) – tumoraal in CU Sulfasalazine (Salazopyrine)
Goal of treatment
- Change the course of the disease Hit inflammation to avoid structural damage Top down strategies
- Deep disease remission
- Symptoms control
- Avoid complications and surgery Colitis ulcerosa en heelkunde
15 en 40% colectomie
Hoogste kans eerste jaar na diagnose
Voornamelijk pancolitis en ernstige ziekte bij diagnose ziekte
Selby W. Baillieres Clin Gastroenterol 1997;11:53-64 Crohn en heelkunde
60% heelkunde binnen 10 jaar na diagnose
± 20-40% zullen binnen de 5 jaar na heelkunde opnieuw heelkunde
± 40-70% zullen binnen de 15 jaar na heelkunde opnieuw heelkunde nodig hebben
2/3 van de crohn patiënten zullen minstens 1 * heelkunde nodig hebben gedurende hun leven
Sales DJ, Arch Inter Med 1983;143:249-299 Operaties voor IBD ?
Nemen af in aantal ? Blijven status quo ? Nemen toe ? Trends in Surgery for Crohn's Disease in the Era of Infliximab. Jones, Douglas; Finlayson, Samuel; MD, MPH
Annals of Surgery. 252(2):307-312, August 2010. DOI: 10.1097/SLA.0b013e3181e61df5
Jaarlijkse database (NIS) in USA : aantal chirurgische procedures + hospitalisaties voor ziekte van Crohn
Trends in surgery for Crohn’s Disease (1993-2004) Results
38% toename van opnames voor Crohn tussen 1993 en 2004
Lichte daling van de gemiddelde leeftijd
Daling van de hospitalisatieduur van 8 naar 5,7 dagen
59% ♀ FIGURE 1. Colorectal resections. Trends in population-based rates of colorectal resections in patients with Crohn's disease from 1993 FIGURE 2. Fistula repairs. Trends in population-based FIGURE 3. Incision of perianal abscess. Trends in population-based rates of to 2004 using classification in Table 1. rates of fistula repairs in patients with Crohn's disease incision of perianal abscess in patients with Crohn's disease from 1993 to 2004 from 1993 to 2004 using classification in Table 1. using classification in Table 1.
Meest frekwente ingreep : rechter hemicolectomie Op de 15 meest frequente type ingrepen: Colorectaal (9) fistel herstel (3) dundarm (2) drainage een anaal abces (1) Surgery, Crohn's Disease, and the Biological Era: Has There Been an Impact?. Slattery, Eoin; MD, MRCPI; Keegan, Denise; Hyland, John; MCh, FRCSI; ODonoghue, Diarmuid; MD, FRCPI; Mulcahy, Hugh; MD, FRCPI
Journal of Clinical Gastroenterology. 45(8):691-693, September 2011. DOI: 10.1097/MCG.0b013e318201ff96
IBD database of St. Vincent’s University Hospital, Dublin, Ireland: 722 patients
20 jaar periode (1986-2005): onderverdeeld in 4 periodes (quartiles) en resecties waren gerapporteerd 1 en 3 jaar na diagnose
Introduction of biologicals (infliximab): multiple RCT: response rates of more than 60% Effect on intestinal resection ? FIGURE =1 . Surgical rates at 1 and= 3 years from diagnosis *P=0.03, [yen]P=0.963.
= = Geen invloed van Infliximab op vroege darmresectie Type heelkunde veranderde niet over de jaren: 60% ileocolische resecties 25% colectomieën 20% geïsoleerde dundarmresecties
2
Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial (LIRIC trial)
Ponsioen et al. Lancet gastroenterology and hepatology, 2017
4 y follow up: Resection (N=72): 26% received IFX Infliximab (N=70): 37 % needed surgery Ulcerative colitis Definition and evolution
Ulcerative colitis: a chronic inflammatory disorder of the colonic mucosa, usually beginning in the rectum and extending proximally to a variable extent. Management
General principles
• Majority controlled by medical management; surgery is usually only required for poor control of symptoms or complications.
• Acute attacks require close scrutiny to avoid major complications
• Long-term colitis carries a risk of colonic malignancy Management
Surgery
Indications
• Failure of medical treatment to control chronic symptoms
• Complications: profuse haemorrhage, perforation/toxic megacolon, risk of cancer (greater with longer disease, more aggressive onset and more extensive disease)
• Dysplasia or development of carcinoma. Fulminating colitis
• Faecal residue never accumulates in an inflamed segment • Absence of faecal residue suggests total colitis • Toxic megacolon usually involves the transverse colon • Normally the transverse Ø does not exceed 5,5cm • in toxic dilatation > 6,5cm • obliteration of the normal haustra • If intramural air is seen, it signifies impending perforation. Toxic megacolon
7-17% of patients requiring hospitalization
Lifetime incidence of 0,5%-2,5%
Mortality only 0,2% over 4 year follow-up (50% of all colitis ulcerosa deaths)
Severly ill patients can have toxic symptoms without dilation, with impending perforation difficult to predict (cave lack of symptoms due to high dose steroids).
Mortality of perforation 27-57% Severe colitis
Up to 88% will avoid surgery 48-96% has an adequate trial of medical therapy
Surgical criteria: > 8 bowel movements/day or 3-8 bowel movements with a CRP > 45 ng/ml despite 3 days of medical therapy (1)
Incomplete response within 7 days of medical management, 60% chance of continuing colitis and 40% chance of colectomy within 1 year (2).
1) Wexner SD, Dis Colon Rectum 1997;40:1277-1285 2) Travis SP, Gut 1996;38:905-910.
Urgent intervention for colitis ulcerosa
Total abdominal colectomy with end ileostomy, postoperative complication rate: 23-33%, mortality: 0-4%.
Rectal stomp management: 12% rate of pelvic abscess with an intraperitoneal rectal stomp and 4-7% if exteriorized (1). Not if routine transanal drainage; proctectomy rarely required at emergency (2).
(1) Carter FM, Dis Colon Rectum 1991;34:1005-1009 (2) Karch LA, Dis Colon Rectum 1995;38:635-639.
Number of patients found to have Crohn disease instead of colitis ulcerosa is appreciable. Colitis ulcerosa and carcinoma
Overall cancer incidence 3,7% and 5,4% in pancolitis rises with: • Longer duration of disease symptoms
Indications for surgery: Established carcinoma High grade dysplasia and DALM (dysplasia associated lesions or mass) . Because of high incidence of synchronous cancer (43%). Low grade (?) Bernstein CN, Lancet 1994;343:71-74
Stricture (20-24% malignant; biopsies inadequate to rule out). Cohen JL, Dis Colon Rectum 2005;48:1997-2009. Elective surgery
1) Persistent acute colitis
2) Recurrent relapse
3) Chronic disease involving the whole colon (anemia, lassitude, urgency, diarrhea, weight loss)
4) Side-effects of medical R/
5) Impaired lifestyle
6) Some extra intestinal manifestations
7) Repeated high grade dysplasia/carcinoma. Elective surgery for colitis ulcerosa and extra-intestinal manifestations
Ameliorated : mono articular arthritis, uveitis quid iritis
Not improved : PSA, ankylosing spondilytis and sacroileitis
Variable : erythema nodosum, pyoderma gangrenosum. Surgical techniques: Kock pouch
29% conversion to conventional ileostomy at 29 years
51% one revision, 19% more than one
71% long term success (similar to that of IPAA).
Distal division of SMA (if marginal arcades ok) Surgical techniques: IPAA (ileal pouch anal anastomosis) +- ileostomy Surgical techniques: IPAA (ileal pouch anal anastomosis) +- ileostomy
Stapled anastomoses
1,5cm above the dentate line
Hand sewn versus stapled anastomoses in colitis ulcerosa
Mucosectomy led to unnecessary anal sphincter and nerve damage with minimal benefit in terms of disease control. Mucosectomy: higher incidence of nocturnal sheepage and usage of pads. Manometric measures suggested that resting and squeeze pressures were significantly reduced.
Lovegrave RE, Ann Surg 2006;244:18-26. Surgical techniques: IPAA (ileal pouch anal anastomosis)
Benefit: Removal of disease up to the anal transition zone Maintenance of a normal pathway for defaecation Avoidance of a perineal wound and permanent stoma
Disadvantage: Need for a second operation to close the deviating loop ileostomy Need for continued surveillance of the residual anal transition zone Ongoing management of bowel function.
IPAA: Complications
Low postoperative mortality rate of 0,2-1%
Anastomotic separation 5-10%
Ileal pouch vaginal fistulas 3-10% in ♀ High failure rate of treatment (50%) 21% pouch excision Often with anastomotic dehiscence
Ileo-pouchitis/ ulceration/ stenosis IPAA: Pouch survival J Gastrointest Surg. 2017 Jan;21(1):56-61. doi: 10.1007/s11605-016-3306-9. Epub 2016 Nov 10 IPAA:routine diversion ?
Omission in good conditions. Patient: relatively healthy, well nourished not anaemic not on high dose steroids. Intra-operative factors: well-vascularized small bowel low blood loss haemodynamic stability tension free anastomoses
Renize FH, Dis Colon Rectum 2006;49:470-477 Surgical techniques: IR (ileorectal anastomosis)
57% ultimately failed (mostly to ongoing rectal inflammation). Gastroenterol Res Pract. 2016;2016:5832743. Epub 2016 Oct 23 Surgical techniques: Ileostomy IPAA: Pouchitis
Crohn’s disease Differential diagnosis of Crohn colitis
• Ulcerative colitis
• Infectious colitis
• Ischaemic colitis : usually segmented, commonly involves the splenic flexure
• Sexually transmitted colitis
• Diversion colitis (R/ short claim fatty acids)
• Radiation colitis
• Collagenous colitis Crohn’s disease
3 major subtypes:
fibrostenotic diseases fistulizing agressive inflammatory. Indications for surgery in Crohn
43% chronic obstruction
22% fulminant colitis
29% chronic colitis.
12% abces
3% fistula
1% bleeding
Small bowel disease
feeling between thumb and index at mesenteric side
no difference in endoscopic and symptomatic recurrence between stapled side to side anastomoses versus manual ÉTÉ anastomoses in CD (McLeod 2007, Dis colon and rectum 2009) (isoperistaltic anastomoses can be more easily dilated endoscopically)
90 % recurrence free disease survival at 60 months after primary ileocolic anastomosis
anastomoses be constructed between segments of bowel grossly free of active disease Small bowel disease
Histologic examination: - active/chronic inflammation in lamina propria - Granuloma - Paneth cells in the ileal crypts - Lymphatic vessel density in the mucosa/submucosa - Submucosal plexitis - Myenteric plexitis
Histologic examination can aid in select patients for early restart of medical treatment Small bowel disease
KONO-S anastomoses (2011) Small bowel disease: what about the mesentery ?
Is crohn a primary mesenteropathy: the outside – in theory ?
in conflict with efficacity of stricturoplasty where the mesenterium stays in
Stricturoplasty Stricturoplasty Stricturoplasty
Indications: Short fibrous strictures Diffuse involvement of small bowel involving multiple strictures History of diffuse prior small bowel resections Duodenal Crohn’s disease. Not be done: Multiple strictures within a short segment A long (> 20cm) stricture A stricture close to a side of resection Perforation, fistula and phlegmon at the site of stricture. Fate of plasty? Recurrence in 5% of cases (disease regression?). Overall morbidity: 22% (leak, fistula or abscess) in 11% in a follow-up of 85 months. Feamhead NS, Be J Surgery 2006;93:475-482
Abscess in Crohn’s disease
Lifetime risk 25%
Can often be drained percutaneously
To be followed by surgery of the associated diseased bowel (?) Temporary defunctioning ileostomy
High incidence of disease remission
but for the majority of patients the prospect of future restoration of intestinal continuity is limited in the initial operative management in the severely ill patient with Crohn’s colitis segmental colon resection. Intestinal fistulas
General principle:
Resection of the primarily affected diseased segment And closure of the defect in the secondarily involved again.
Ileosigmoid ileum ! Colojejunal colon ! Fistula
infrequently an isolated indication for surgery
accompanied by abces, masses, obstruction, peritonitis (rare)
entero-enteric fistulas, no surgery unless significant sequelae of malabsorption. Anal Fistula
Infliximab: direct evidence – accent II trial AB: metronidazole - Quinolones Removement ?
56,5% vs 38 % remission at 1 y
LIFT = ligation of interspincteric Advancement flap fistula tract Adenocarcinoma of the small intestine and Crohn’s disease
Rare (12-60 fold risk)
Poor prognosis
30-60% mortality at 1-2 years
Biopsy in stricturoplasty! Colonic disease
Segmental colonic disease may be adressed with segmental resection, 17% from strictures (7-10% malignant), risk of colorectal carcinoma lower than in colitis ulcerosa (older age at diagnosis, duration of disease, pancolitis).
Diffuse disease require proctocolectomy with ileostomy or total abdominal colectomy with ileorectostomy (if distal rectum diseasefree) In patients with diffuse colitis and proctitis, total proctocolectomy compared to abdominal colectomy or segmental has been associated with: less medication use increased time interval to first recurrence.
IPAA is associated with a significantly higher rate of morbidity (pouch failure, incontinence and pouchitis) than colitis ulcerosa.
Toxic colitis has simular presentation to that in colitis ulcerosa. Colectomy with ileorectal anastomosis
In 25-50% of patients with Crohn colitis if rectum is not severely diseased
At 10 years: 64% recurrence 48% reoperation rate Proctocolectomy intersphincteric plane Proctocolectomy intersphincteric plane:
The mesorectal is different in CD vs CU:
Persistent inflammatory activity is associated with complications in proctectomy for CD (Dhoore et al., PG RBSC 2018)
→ TME type resection, omental flap Laparoscopy and Crohn disease
laparoscopic group: pulmonary function tests normalised more rapidly return of gastrointestinal function and length of stay not significantly different.
Milsom JW, Dis Colon Rectum, 2001;44:1-8.
operation time longer median hospital time shorter costs lower quality of life not different.
Maartense S., Ann Surg 2006;243:143-149 - Proven efficacy of biological in mild disease → more complex cases for surgery
- More comorbidity – preoperative steroids- anti-TNF → no increase in postoperative morbidity
- By more laparoscopy and less blood loss ?