IBD-WHEN SHOULD THE SURGEON BE INVOLVED ? https ......BIOLOGICS-GROWTH •IFX improves linear height...

IBD-WHEN SHOULD THE SURGEON BE INVOLVED ?

Dr George Alex

Consultant Paediatric Gastroenterologist

Head of IBD

Royal Children’s Hospital Melbournehttp

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DISCLOSURE

• Not a surgeon

• “Wannabe surgeon” till this year.

I APPSPGHAN - PIBD Materclass2

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CHILDHOOD ONSET IBD IS SYNONYMOUS WITH:-

• Extensive inflammation

• Aggressive and progressive disease

• Growth failure


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NATURAL HISTORY OF CROHN’S DISEASE


“Stricturing/Penetrating disease is-

synonymous to surgery”

Vernier M et al Gastroenterology 2008

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LIKELIHOOD OF NEEDING SURGERY IN CHILDHOOD ONSET IBD

CROHNS

• Patients diagnosed with Crohn’s

PHYSICIANS’ DREAM

• That aggressive medical management can change the natural history and prevent surgery (delay the inevitable)?


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Improved medical treatment (Pre biologics) led to a downward trend of surgical resection rates for CD from 59% to 25% in a Cardiff Study 1986-2003


Early thiopurine use !?

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WHAT ELSE DID WE AS PHYSICIANS DO AFTER THAT ?”

“Bring out our best weapon” in early 2000

Introduced biologics- anti-TNF-alpha e.g. infliximab


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BIOLOGICS-WHAT WE KNOW IT CAN DO/ WHAT WE HOPE FOR IT TO DO?

• Resolves inflammation- proven endoscopically, radiologically. ? translates to less surgery…..-

• Changed the way in which perianal CD is managed and are currently our most effective pharmacological class of drugs for this particularly debilitating manifestation…. ? translates to less surgery

• Effects on Growth- Poor growth- multifactorial etiology -uncontrolled inflammation- increased cytokine production [eg,IL-1b, IL-6, TNF-a] that impairs hepatic expression of insulin-like GF1 which in turn results in GH resistance in chondrocytes


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BIOLOGICS-GROWTH

• IFX improves linear height ◦ REACH study height z-scores improved by 0.5 @ 54 weeks. (Cohort of patients with 1year delay in bone age )

• Walters T et al- 27 children (18 male) with otherwise refractory Crohn’s who received maintenance infliximab found that height and height velocities are most improved when treatment is initiated before or during early puberty (Tanner I-III). Treatment has a lesser effect on growth later in puberty (Tanner IV, V).

• Malik et al small study of 28 children showed- In those that responded to infliximab therapy (75%) there was an improvement in linear growth in the short term. This increase may be unrelated to progress in pubertal status or reduction in GC dose. They also showed a similar effect with Adalimumab

• Hyams J et al 2007, Malik et al 2011 and 2012, Walter T et al 2007


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ANTI-TNF a- WAS INTRODUCED IN 2001-2004

EARLY EVIDENCE ON THE EFFECTS OF ANTI-TNF ON SURGERY RATES……


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• Real world data in

Canada published in

2019 on the use of

biologics in adults.

Data 1995- 2012 in adults

• No significant reductions

comparing CD patients on infliximab and not

over 10 years with

regards to:

• CD-related

hospitalisations

• Rates of intestinal

resections.

In UC-5 year data no

change in colectomy

rates with infliximab but

less hospitalization

Significant increase in

drug costht

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Large nationwide

Danish study in

children showed a

drop in surgery rates in

UC but not Crohn’s

with use of anti-TNF.

Patients were followed

from 1998- 2013

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Time from diagnosis of Crohn’s disease to first-time surgery for children diagnosed before age of < 17 years, stratified in four calendar periods, n = 1278 children. Using the Cox proportional hazards regression analysis, the rate of surgery after the introduction of anti-TNFα agents [by January 1, 2004] was not significantly different compared with the rate of surgery before the introduction of anti-TNFα agents [hazard ratio: 0.91, 95% CI: 0.62–1.33].

Time from diagnosis of ulcerative colitis to first-time surgery for children diagnosed before age of 17 stratified in four calendar periods, n = 1468 children. The rate of surgery after the introduction of anti-TNFα agents [by July 1, 2005] was significantly different compared with the rate of surgery before the introduction of anti-TNFα agents [hazard ratio: 0.64, 95% CI: 0.47–0.86].

Due Larsen JCC 2016

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• Early results of biologics was DISSAPPOINTING

• Change in strategy………..


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IBD 2011, Gastroenterology 2017

Concept- Early intervention

and window of opportunity

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“WHAT DID WE PHYSICIANS DO –SHARPENED OUR TOOLS?”

• Treat to Target- aim mucosal healing

• Early use of biologics before damage is done- 2011-2015

• Optimize the use of biologics to gain this end- drug monitoring 2016 onwards


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NEWER TRENDS IN USE OF ANTI-TNFa IN PIBD -STARTING TO SHOW PROMISE


1) n=875 ,mean age at diagnosis

13.6 years (1.6‐ 17.6), 2) Prevalence of anti‐TNF‐treated

patients increased from 5.1% to

27.1% (2007‐2017), P = 0.0001.3) Surgical resection‐rate fell

(7.1%‐1.5%, P = 0.001), driven by a decrease in Crohn's disease

resections (8.9%‐2.3%, P = 0.001). Perianal surgery and

ulcerative colitis resection‐rates were unchanged.

4) Time from diagnosis to resection

increased (1.6‐2.8 years, P = 0.028)

5) Patients started on

anti‐TNF‐therapy

DO WE (STILL) NEED SURGEONS IN 2020?

YES


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POINTS TO BEAR IN MIND

Surgery in Crohn’s disease is not CURATIVE relapse occurs at anastomotic sites and elsewhere


Danish cohort of 115 children

undergoing resection cumulative

clinical recurrence of 50%,73%

and 77% at 1,5,10 years.

Recurrence defined by PGA and

requiring escalation of therapy or

second surgery (34% within

median time to second surgery of

26 months).

Surgery and Postoperative Recurrence in Children With Crohn Disease

Hansen, Lars F.; Jakobsen, Christian; Paerregaard, Anders; Qvist, Niels; Wewer, VibekeJournal of Pediatric Gastroenterology and Nutrition60(3):347-351,

March 2015.

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https://journals.lww.com/jpgn/Fulltext/2015/03000/Surgery_and_Postoperative_Recurrence_in_Children.17.aspx

WHEN DO WE CALL THE SURGEONS?

• Refractory Inflammation → any part of bowel (failed medical therapy both UC and CD)

• Strictures → obstruction (CD)

• Fistulas and abscess/phlegmon (CD)

• Toxic megacolon (UC)

• Perforation (UC and CD)


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COMMON SURGERIES IN THE CONTEXT OF IBD


Ileocaecal resection-Right hemicolectomy

If close to IC valve

small bowel resection for-Ileal/Jejunal

strictures/stricutroplastyif multiple segments

Setons and drainage

Fistulizing disease/Abscess

Defunctioningileostomy

Colectomy- various stagesht

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SURGEONS AND REFRACTORY CROHN’S

Refractory Crohns is disease with ongoing symptoms despite

• optimized maintenance therapy (immunomodulators, anti-TNFaagents or other biologicals released for pediatric CD)

• do not sufficiently respond to further trials of induction therapy (corticosteroids, exclusive Enteral Nutrition—EEN) .

E.g. burnt out/fibrostenotic stricture at the ileocaecal region.

Cross sectional imaging such as MRE will be very useful to determine length, disease burden and hence a roadmap to surgery.

Guide to who will need surgery- stricture length>5cm, bowel thickness at stricture>1cm and proximal dilatation >3cm (? 5cm)

Type of surgery - RESCETION Versus STRICTUROPLASTY more proximal small bowel disease and multiple segments, helps maintain bowel length. If close to IC valve- Right hemicolectomy


Schulberg et al JGH 2020

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Growth failure ?

• Multiple studies mainly in the pre-biologic era showed good growth and nutritional status improvement by 6 and 12 months after surgery, with a significant increase in weight and height z scores.

• Surgery may have an added benefit in patients with localised refractory ileal disease, coupled with growth failure where despite optimal medical and nutritional therapy. Surgery can potentially induce remission and enable catch up growth. “Derailed by Biologics”

• Hojsak I, 2010; Singh Ranger G, et al. 2006;


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LIR!C TRIAL-LONG TERM F/U DATA

• The LIR!C trial showed that laparoscopic ileocecal resection is a cost-effective treatment that has similar quality-of-life outcomes to treatment with an anti-tumor necrosis factor (TNF) drug,” –(Non stricturing, inflammatory terminal ileal disease and immunomodulator refractory (

“PHYSICIANS LAST ATTEMPT”- ENDOSCOPIC BALLOON DILATATION/STICTUROTOMY

Picking the right candidate with a stricture that will benefit the most (usually post operative anastomotic strictures) -90% short term success delays surgery by 6 years

• Patients who are not acutely ill:

• symptomatic, short (≤4 cm),

• straight,

• endoscopically accessible,

• benign and fibrotic (rather than inflammatory)

I APPSPGHAN - PIBD Materclass26 Lan N, Bo Shen Gastroenterology Rep 2020

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I APPSPGHAN - PIBD Materclass27 Rieder F Gut 2013

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SURGEON AND FISTULIZING DISEASE


• Perianal disease-skin tags, fissure, anal stenosis, abscess/fistula- involves 17-43% of patients with CD

• Multi D approach- experienced surgeon and good radiologist (MRI, USS- perianal, transrectal)

• EUA, drainage of abscess and insertion of seton

• Timing important in relation to biologics• Make sure no pelvic sepsis before starting

biologics- all abscess drained, non cutting setons inserted and generally on oral antibiotics leading up to and beyond 2nd

infusion of biologics. Success 70% by 54 weeks• Goal- closure of fistula. If refractory with

recurrent sepsis- consider diversion of faecal stream-stoma

• Removal of seton- individualized 3-8 months

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SURGEON AND ULCERATIVE COLITIS

Elective situation

• chronically refractory to medical therapy,

• unacceptable side effects of medical therapy iesteroid dependence

• and rarely in dysplasia or malignancy

Proctocolectomy and Pouch formation(IPAA) in conjunction with an ileostomy which is subsequently reversed- Laparoscopic good cosmesis and shorter length of stay.

(As physicians we have sleepless nights before making the desicion of the initial colectomy but to patients they feel so much better after the operation)


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EMERGENCY UC SURGERY

Acute severe colitis- initial presentation in 9%-15% of children with UC. IV steroids is the 1st line found to be most important in reduction of mortality in UC (Truelove SC et al. Lancet 1974 Aloi M et al. JCC 2013, Schecter A et al Gut 2015)

• 2 scenarios to call the surgeons

• Failure to respond to 1st (steroids) and 2nd line therapy (Tacro/CyA, anti TNFa)- (2nd line agents have reduced colectomy in the short term to 10-20% but ultimately 50-60% of ASC treatment responders will undergo a colectomy by 2 years)

• Visceral perforation or toxic megacolon (transverse colon diameter >56mm or >40mm in children less than 10 years alongside systemic toxicity (fever, tachycardia). Small allowable window 24-72 hours if clinically stable with toxic megacolon (Turner et al JPGN 2018)


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TYPES OF SURGERY INVOLVING THE COLON

Surgery done in the emergency situation- subtotal colectomy and ileostomy formation (rectum is left behind and oversewn proximally)

Subsequent surgeries

• 2nd stage Proctectomy with Ileoanal J pouch (IPAA) or straight/Ileoanal/rectal anastomosis

• 3rd stage Closure of stoma

Surgery in UC is CURATIVE but associated not uncommonly with complications- Leaks, bleeding, SBO, sepsis

Pouch issues- anastomotic leak, stenosis, abscess and pouchitis, cuffitis

The experience of the surgeon is associated with the likelihood of development of chronic pouchitis; (15%) in surgeons with 10 surgeries/year versus (41%) in surgeons with less than 10 years

(Kelay et al Trans Paediatrics 2019)

Outcomes of surgery also dependent on nutritional state and concurrent steroid use.


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HANDY TIPS ON HOW TO PICK YOUR SURGEON

• Most experienced in colorectal surgery amongst Paediatric surgeons

• Identify 1-2 surgeons and involve them in your regular multi-D meetings

• In 2020 –skill full in laparoscopic surgery

• Willing to work with Adult Colorectal surgeons


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CONCLUSION

• In 2020 Surgeons are still paramount in the management of IBD both in Crohn’s and Ulcerative Colitis

• Involve them early and keep them informed and make them a part of your IBD multi D meetings.


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IBD-WHEN SHOULD THE SURGEON BE INVOLVED ? https ......BIOLOGICS-GROWTH •IFX improves linear height...

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