Postoperative Crohn’s Disease Recurrence and Role of Endoscopy

List of Abbreviations

AGA

The American Gastroenterological Association

CD

Crohn’s disease

CI

Confidential interval

ECCO

European Crohn’s and Colitis Organisation

POCER

Postoperative Crohn’s endoscopic recurrence

TNF

Tumor-necrosis factor

Introduction

Many patients with Crohn’s disease (CD) will require intestinal resection surgery at some point in their disease course. Overall rates of surgery for CD as high as 80% when including tertiary care centers have been reported while a recent systematic review of population-based studies found that risk of requiring surgery after a diagnosis of CD was 16% at 1 year, 33% at 5 years, and 47% at 10 years. Unfortunately such surgery is usually not curative as CD typically recurs. The frequency of postoperative recurrence depends on definitions used. Recurrence is typically first detected on endoscopic or radiologic studies and has been noted as early as 3 months postoperatively ( endoscopic recurrence ) while recurrence of symptoms ( clinical recurrence ) and the need for further surgical resection ( surgical recurrence ) typically follow later in the postoperative course. Endoscopic recurrence rates can be as high as 70%–90% at 1 year following surgery, clinical recurrence rates can be as high as 20%–30% at 1 year, and the need for repeat surgery occurs in anywhere from 35% to 70% of patients at 10 years.

There have been many studies trying to elucidate risk factors for postoperative CD recurrence often with conflicting results. Among these potential factors, current smoking, pathologic findings of granulomas or myenteric plexitis, a perforating disease phenotype, presence of perianal disease, and the creation of an anastomosis appear to be most predictive for an increased risk of disease recurrence. Among these factors, the only modifiable one is smoking. A metaanalysis demonstrated a twofold increase in postoperative clinical recurrence and a 2.5-fold increase in the risk of further surgery by 10 years in smokers compared to nonsmokers. Furthermore, smoking cessation has been correlated with a decreased risk of postoperative recurrence.

The other main issue in management of postoperative CD relates to deciding which patients need postoperative medical therapy, the timing of such treatment, and which therapy to use. There have been multiple studies evaluating postoperative medical therapy, sometimes with conflicting results.

In this review, we will discuss the approaches to optimal management of CD following surgery with a particular focus on the diagnostic and therapeutic role of colonoscopy in this setting. Review of recently published key medical prophylaxis clinical trials and guidelines will be discussed.

Endoscopy in Guiding Management of Postoperative Crohn’s Disease

Endoscopic examination after surgery for CD has been shown to be useful for both diagnostic and risk stratification purposes. Endoscopic recurrence typically precedes clinical symptoms in the postoperative setting with endoscopic recurrence rates of disease in the neoterminal ileum reported to be as high as 70%–90% at 1 year after ileocolonic resection and anastomosis. An important study done to evaluate the pattern of endoscopic recurrence, followed 114 patients who had serial colonoscopies after undergoing ileocolonic resection. Seventy-seven percent of patients developed endoscopic recurrence with disease typically confined to the neoterminal ileum and anastomosis. Within 1 year after surgery the most common endoscopic finding was aphthous ulcers which were found in 76% of those with endoscopic recurrence while more advanced lesions of nodules and large ulcers were noted in 24%. However, over time, there was a progression of endoscopic lesions with nodules and larger linear or serpiginous ulcers developing more frequently over 1–3 years. Finally, in patients examined more than 3 years after surgery, 46% had developed a rigid, ulcerated stenosis of the anastomosis and/or the neoterminal ileum. This study nicely highlights the typical progressive pattern of endoscopic recurrence from mild to severe disease after ileocolonic resection for CD.

In a follow-up study published in 1990 that remains important to this day, Rutgeerts et al. followed 122 CD patients who had undergone a first or second ileocolonic resection and received no initial postoperative medical therapy. Patients had a colonoscopy to the neoterminal ileum within the first year after surgery, and the findings were scored based on an endoscopic scoring system that is still used in current practice and has been named the Rutgeerts endoscopic score ( Table 25.1 ; Fig. 25.1 ). The endoscopic score at the first follow-up colonoscopy examination was the most strongly associated variable for risk of subsequent symptomatic recurrence. Specifically those with no (i,0) or mild recurrence (i,1) within 1 year did very well on follow up with a low risk of symptomatic recurrence over the next 5 years. However, those with more advanced endoscopic recurrence such as diffuse aphthous ileitis/inflammation (i,3) or large ulcers, nodules, and/or narrowing (i,4) had very high rates of symptomatic recurrence on follow-up. In fact, all patients with an i,4 endoscopic score developed symptomatic recurrence within 4 years of surgery. Correlating with this, the severity of endoscopic recurrence within 1 year of surgery also predicted the evolution of progression of endoscopic scores at repeat colonoscopy 3 years postoperatively ( Table 25.2 ).

Table 25.1

The Rutgeerts Endoscopic Scoring System

Classification	Endoscopic Description
i,0	No lesions
i,1	Less than five aphthous ulcers
i,2	More than five aphthous ulcers with intervening normal mucosa or Skip areas of larger lesions or Lesions confined to the ileocolic anastomosis
i,3	Diffuse aphthous ileitis with diffusely inflamed mucosa
i,4	Diffuse inflammation with large ulcers, nodules, and/or narrowing

Table 25.2

Comparison of Large, Randomized Trial for Medical Prophylaxis of Postoperative Crohn’s Disease Recurrence

	N	Endoscopic Recurrence Rates ^a			Clinical Recurrence Rates
	N	Placebo	Treatment	P -value	Placebo	Treatment	P -value
TOPPIC ^b^,	240	49%	43%	0.38	23%	13%	0.07
PREVENT ^c^,	297	51%	22%	<0.001	20%	13%	0.097

a Endoscopic recurrence defined as a Rutgeerts endoscopic score of i2 or greater.

b Recurrence within 3 years postoperatively.

c Recurrence at 1 year postoperatively.

Therefore, it can be seen that endoscopic examination of the ileocolonic anastomosis and neoterminal ileum plays an important role for both diagnosis and risk stratification with the severity and extent of endoscopic recurrence being strongly associated with clinical recurrence risk. Based on such evidence, endoscopic monitoring for disease recurrence has been adopted as one potential strategy after surgery for CD. Recommendations regarding the use of endoscopy to guide decision-making in the postoperative setting have been incorporated into societal guidelines include those of the American Gastroenterological Association (AGA) and the European Crohn’s and Colitis Organisation (ECCO) as follows:

The American Gastroenterological Association

•

“In patients with surgically induced remission of CD not receiving pharmacological prophylaxis, the AGA recommends postoperative endoscopic monitoring 6–12 months after surgical resection over no monitoring.” (Strong recommendation, moderate quality of evidence.)
•

“In patients with surgically induced remission of CD with asymptomatic endoscopic recurrence, the AGA suggests initiating or optimizing anti-TNF and/or thiopurine therapy over continued monitoring alone.” (Conditional recommendation, moderate quality of evidence.)

European Crohn’s and Colitis Organisation

•

“Ileocolonoscopy is the gold standard in the diagnosis of postoperative recurrence by defining the presence and severity of morphologic recurrence and predicting the clinical course [EL2]. Ileocolonoscopy is recommended within the first year after surgery where treatment decisions may be affected [EL2]”

Supporting such recommendations are the results from a randomized postoperative Crohn’s endoscopic recurrence (POCER) trial, in which 184 consecutive patients undergoing surgical resection with an endoscopically accessible anastomosis were included. All patients received postoperative treatment with metronidazole for 3 months and were stratified for further drug therapy based on predefined criteria for high versus low risk of recurrence. Those categorized as high risk received treatment with either azathioprine or adalimumab. All patients were then randomized in a 2:1 ratio to either undergo a colonoscopy at 6 months following surgery (active care) or to no colonoscopy at 6 months (standard care). In the active care group, endoscopic findings at 6 months dictated potential changes in medical therapy. The primary endpoint was endoscopic recurrence at 18 months after surgery defined as a Rutgeerts score of i2, i3, or i4 ( Table 25.1 ). Modified intention-to-treat analysis showed that the active care group had a lower rate of endoscopic recurrence at 18 months (49%) compared to the standard care group (67%); P = .03. Furthermore, 22% of patients in the active care group had no evidence of mucosal disease (i0 score) at 18 months compared to 7% in the standard care group; P = .03. Among patients in the active care group, 47 of 122 (39%) had a step up in treatment based on the results of the colonoscopy done at 6 months demonstrating the important role of colonoscopy in guiding therapeutic decisions. Of these patients, 38% achieved endoscopic remission at 18 months. However, it is also important to note that endoscopic remission at 6 months was still associated with subsequent endoscopic recurrence in 41% of patients 1 year later, emphasizing the importance of continued monitoring. However, this also brings up the possibility that colonoscopies may have been performed too early after surgery and perhaps waiting for a 12-month endpoint would have affected this finding. In summary, the results of the POCER study provide the first prospective, randomized evidence that endoscopy can guide postoperative CD management to lower the risk of recurrence.

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