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10 Colonic Dysplasia in Patients with Ulcerative Colitis: Endoscopic or Surgical…
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individual risk of progression in UC patients. Long term outcomes data on endoscopic vs surgical management of dysplasia in UC are needed to understand when
to perform endoscopic treatment versus radical surgical treatment. While surgery is
denitive treatment for patients with UC with oncologic implications, total proctocolectomy is associated with 1% risk of perioperative mortality and long term
changes in urinary, sexual and defecatory function with signicant impact on quality of life [46].
121
Recommendations Based ontheData
UC patients with dysplasia should be managed in a multi-disciplinary setting,
including IBD gastroenterologist, advanced endoscopist, pathologist and an IBD
surgeon.
Most visible dysplastic lesions are amenable to endoscopic resection which
should be performed by advanced endoscopists with expertise in EMR and ESD
[47], with the aim to achieve an en bloc resection with negative margins to reduce
the risks of recurrence [48]. For lesions larger than 20 mm, or where EMR is
unlikely to be successful in achieving an en bloc resection, ESD is a valid alternative [47]. However, ESD of dysplastic lesions has additional procedural risks quantied as 6.7% major bleeding rate and 2.9% perforation rate [27], that are usually
managed successfully at the time of endoscopy.
If endoscopic resection of the all dysplastic lesions present is successful, and
there is no dysplastic change in the at mucosa surrounding the lesion(s), these
patients should undergo regular endoscopic surveillance, due to low risk of CRC
after complete endoscopic resection of dysplasia [49–50]. If histology conrms
<1cm polypoid LGD lesions, the next surveillance colonoscopy can be performed
at 1year. For HGD lesions, endoscopic resection is efcacious, although their presence is associated with risk of synchronous CRC of 15% [51] and for this reason a
re-examination of the resection site for dysplastic recurrence should be undertaken
after 3–6months.
If the resected lesions have features of submucosal invasion, or contain signicant submucosal brosis limiting endoscopic resection (including irregular surface
architecture, mucosal depression, radiating folds or failure to lift with submucosal
injection) en block resection is difcult to be achieved and these patients should be
considered for a colectomy. Figure10.2 summarises our current clinical approach to
the management of visible colitis-associated dysplasia.
If invisible dysplasia is detected, then a repeat high-denition chromoendoscopy
in an optimally-prepared patient should be performed by an experienced endoscopist. Invisible LGD is an independent predictor of long-term progression to advanced
neoplasia in multivariate analyses (two to three-fold increased risk) [45, 50].
Invisible HGD is an indication for colectomy due to the high associated CRC
risk [52].
When surgery is advocated, total proctocolectomy is the preferred surgical
approach, due to multifocal risk of cancer. The role of segmental colectomy or
122
Visible IBD dysplasia
En-bloc resecon IS N
•
•
•
olonoscopy
If perilesional
mulf
MDM and consider
COLECT
endoscopists
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L. Ferrari and A. Fichera
Fig. 10.2 Flowchart of the management of visible colitis-associated dysplastic lesions
rectum sparing surgery in patients with UC and dysplasia remains controversial due
to the high rates of synchronous and metachronous neoplasia.
A Personal View oftheData
Colorectal cancer progression remains an area of concern in patient with UC and it
is considered the most feared complication in patients with long standing colitis.
Combining the aging population of UC patients with improved endoscopic techniques and increased use of medical treatment, dysplasia detection rates by experienced endoscopist can exceed 10% [53].
advocated with involvement of expert IBD gastroenterologist, interventional endoscopist, IBD pathologist and IBD surgeon. Patients should be counselled about risk
of metachronous neoplasia despite continuous surveillance and successful endoscopic resection. Patients should receive information about lesion-specic and
patient- specic risk factors.
histologically-conrmed HGD, multifocality, invisible dysplasia, large (≥10mm)
lesion size, and non-polypoid morphology [44, 45, 54]. Patient-specic risk factors
include presence of PSC, previous dysplasia, signicant uncontrolled mucosal
inammation, limitations to adequate mucosal assessment (e.g. colonic stricturing
or pseudopolyposis) and a family history of CRC [54]. Fumery etal. [45],in their
systematic review, found that among patients with UC associated LGD under surveillance, the annual incidence of progression to CRC was 0.8%/ Concomitant primary sclerosing cholangitis, invisible dysplasia, distal location, and multifocal LGD
are high-risk features associated with dysplasia progression [45]. All these risks
factors should be discussed with the patient who is enrolled in a surveillance
Limited biopsies of area of uncertainty
Photodocuments dysplasc lesions
Discuss at muldisciplinary meeng (MDM)
ocal dysplasia, rediscuss in
OMY
OT possible at index colonoscopy
dysplasia or
aon for
If features of submucosal
colorectal cancer (CRC) with
invasion, indicaon is for
COLECTOMY WITH
ONCOLOGICAL RESECTION
MARGINS
En bloc resecon IS possible at index c
• Lesion margins less than 10 mm, adequate
lesion view, good bowel preparaon and
moderate inflammaon
FOLLOWING SUCCESSFUL RESECTION
• Surveillance colonoscopy at 3-6 months if
lesion is non-polypoid, less 10 mm or has HGD
• Otherwise for surveillance at 1 year
Features suggesng difficult
en-bloc resecon,
consideraon for endoscopic
mucosal resecon (EMR) or
endoscopic submucosal
resecon (ESD) by advanced
As previously mentioned, a multidisciplinary approach to LGD and HGD is
Dysplasia features associated with higher rates of progression to CRC comprise
10 Colonic Dysplasia in Patients with Ulcerative Colitis: Endoscopic or Surgical…
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123
program, considering that for UC, total proctocolectomy is curative, making the
patient in a position to avoid future medical treatment and their side effects. This is
even more relevant in patients with more than one risk factor considering that neoplasia risk increases cumulatively in the presence of multiple risk factors [44].
Patients with well controlled disease might be reluctant to accept risks of prophylactic total proctocolectomy, with the associated changes in the quality of life.
After multidisciplinary discussion and patient education a share decision approach
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Which Patients Benefit fromBiologic
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Agents toPrevent Disease Recurrence
11
After Resection inCrohn’s Disease?
YusukeMiyatani andAtsushiSakuraba
Introduction
Crohn’s disease is a chronic inammatory condition that affects the entire digestive
tract, resulting in bowel damage such as stricture, stula, and perforation [3]. Up to
80% of patients experience surgery in their lifetime, of which approximately onequarter require a second surgery, often within 5years of their previous surgery [4].
Endoscopic recurrence occurred in about 70% of patients within one year after surgery, which precedes clinical recurrence [5].
On the other hand, the introduction of novel immunosuppressive therapies had
dramatically changed treatment strategies for Crohn’s disease. Biologics are also
deemed effective in preventing recurrence following surgery [1], which has reduced
the rate of reoperation in a cohort study [2]. However, biologics carry risks of
adverse effects and can be of nancial burden both on patients and health care economics. Therefore, individualized evaluations and treatment plans organized by
multidisciplinary team between surgeons and gastroenterologists are imperative to
reduce the risk of postoperative recurrence.
In this chapter, we describe the evidence focusing on risk factors for postoperative recurrence of Crohn’s disease, and treatment options to clarify which patients
benet from biologics to prevent disease recurrence after resection.
Y. Miyatani
Inammatory Bowel Disease Center, The University of Chicago Medicine, Chicago, IL, USA
e-mail: Yusuke.Miyatani@uchospitals.edu
A. Sakuraba (*)
RUSH Center for Crohn’s and Colitis, RUSH University Medical Center, Chicago, USA
e-mail: atsushi_sakuraba@rush.edu
© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2023
K. Umanskiy, N. Hyman (eds.), Difcult Decisions in Colorectal Surgery,
Difcult Decisions in Surgery: An Evidence-Based Approach,
https://doi.org/10.1007/978-3-031-42303-1_11
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Table 11.1 PICO table
P (Patients)
Patients with Crohn’s
disease after resection
I (Intervention) C (comparator)
Prophylaxis with
biologics
Other medications or
no therapy
Y. Miyatani and A. Sakuraba
O (Outcomes)
Postoperative
recurrence
Search Strategy
Table 11.1 demonstrates the PICO process relevant to our research question. We
searched the PubMed database in the English language between 1966 to 2022 with
the following keywords “Crohn’s disease” and “postoperative recurrence”. Each
clinically relevant article was checked as a full-article.
Results
Definition ofRecurrence
Recurrence as an outcome can be mainly divided into three categories: endoscopic,
symptomatic, and surgical recurrence. The denitions of endoscopic and clinical
recurrence can vary in each study as follows:
Endoscopic Recurrence
Rutgeerts score has been most commonly used as a postoperative endoscopic score
of neoterminal ileum which is dened as follows: i0 indicates no lesions; i1 indicates <5 aphthous lesions; i2 indicates >5 aphthous lesions with normal mucosa
between the lesions, or skip areas of larger lesions or lesions conned to the ileocolonic anastomosis; i3 indicates diffuse aphthous ileitis with diffusely inamed
mucosa; i4 indicates diffuse inammation with already larger ulcers, nodules, and/
or narrowing [5]. In most clinical trials, Rutgeerts score ≥i2 was most commonly
dened as endoscopic recurrence, which has been reported to predict future clinical
recurrence [6]. Since the location of inammation (e.g. at the anastomosis or at the
terminal ileum) may inuence the recurrence risk, a recent study analyzed clinical
recurrence by dividing Rutgeerts score of i2 into i2a and i2b in accordance to the
location of inammation. However, this modied Rutgeerts score did not show a
signicant difference regarding the subsequent clinical recurrence and the need for
endoscopic or surgical intervention [7].
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129
Clinical Recurrence
Clinical recurrence is commonly dened as follows: symptoms of active Crohn’s
disease such as diarrhea and abdominal pain, Crohn’s Disease Activity Index
(CDAI) indicated ≥150 or 200, and Harvey-Bradshaw index (HBI) indicates ≥8,
which are occasionally used as a composite outcome [1, 8, 9].
Surgical Recurrence
A new surgery including resection or stricturoplasty of the ileocolic anastomosis is
homogeneously dened as surgical recurrence and reliable [10].
Risk Factors ofRecurrence After Resection
The emergence of biologics has made a positive impact on the reoperation rate of
Crohn’s disease [2]. On the other hand, over-treatment should be avoided with
regard to adverse effects and nancial burden both on patients and society. Therefore,
identifying high-risk patients that truly benet from prophylactic biological treatment should be essential (Table11.2). Here we described the risk factors of postoperative recurrence in Crohn’s disease.
Table 11.2 Established risk factors
associated with postoperative Crohn’s
disease recurrence
Risk factor
Smoking
Penetrating disease > inammatory or
brostenosing disease
Prior bowel resection, especially extensive resection
Multiple surgeries
Prior biologics, especially multiple failure
Short duration of disease since diagnosis or
between prior surgery
Perianal disease
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Y. Miyatani and A. Sakuraba
Biographic Feature
Smoking has been consistently reported to increase postoperative recurrence in
many studies [11, 12]. A meta-analysis showed a two-fold increase in the odds of
clinical recurrence in smokers compared to that in non-smokers, and a 2.5-fold
increase in the risk of further surgical resection within 10years [13]. Interestingly,
current smokers have a higher odds ratio than ex-smokers which suggests smoking
cessation may reduce postoperative disease recurrence [14]. Therefore, patient education for smoking cessation by a multidisciplinary approach should be conducted
for smokers.
Complicated disease phenotypes such as perforation, penetrating, and perianal
disease are regarded as postoperative risk factors [9, 12, 15]. Although those factors
were widely used as patient selection criteria in clinical trials, they have not been
fully validated.
Shorter disease duration before rst surgery was reported as a risk factor for
surgical recurrence [16, 17]. Another study demonstrated that a shorter interval
between rst and second surgery was associated with higher risk for a third surgery
[18]. Although these studies utilized different denitions in terms of duration, a
shorter timing of the need for surgery may suggest a more progressive phenotype.
Age and gender are controversial in regards to postoperative recurrence of
Crohn’s disease [11].
Gut microbiota is considered to affect pathogenesis in Crohn’s disease. Dysbiosis
in the mucosa such as reduction of alpha diversity and increase in pro-inammatory
pathogenic bacteria may be associated with postoperative recurrence [19]. Several
bacteria (e.g. Proteobacteria phylum and the Firmicutes phylum) were reported to
predict endoscopic recurrence, but further study is needed to clarify the role of
microbiome [20].
Genetic factors also may contribute to postoperative recurrence. There is a
variety of single-nucleotide polymorphism (SNP) that predispose the individual
to recurrence of Crohn’s disease. NOD2 has been shown to be associated with not
only disease development and progressive phenotype but with postoperative surgical recurrence [21, 22]. SNPs in CARD15, SMAD3, and CARD8 were also
found as risk factors for postoperative recurrence, but further validation is required
[14, 23].
Preoperative Treatment
Whereas tumor necrosis factor inhibitors (TNFi) brought a paradigm shift in the
treatment of Crohn’s disease, a signicant proportion of patients still require surgery. Previous TNFi exposure as the risk of recurrence is understandable considering the general efcacy of TNFi [9, 24]. Whereas ileocecal resection in uncomplicated
ileitis may be a more benecial treatment option in regards to patient’s quality of
life and long-term surgical recurrence compared with continued TNFi use or
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intensication without surgical resection, patients with a previous history of resection have been considered to have a higher risk of clinical recurrence [9, 11, 25, 26].
131
Surgery
Surgical strategy can inuence the rate of postoperative recurrence. A meta-analysis
comparing laparoscopic resection with open ileocolic resection indicated that the
surgical recurrence rate is not signicantly different between the two groups [27],
while laparoscopic surgery is benecial in that it is less invasive than open surgery
with possibly less postoperative complications [28, 27].
Stapled ileocolonic side-to-side anastomosis is associated with lower surgical
recurrence than end-to-end anastomosis, which might suggest the importance of a
wide diameter of anastomosis [29, 30].
An antimesenteric functional end-to-end handsewn anastomosis (Kono-S anastomosis) has recently been designed to maintain a wide anastomotic lumen and
shape [31]. A recent RCT comparing Kono-S anastomosis and stapled ileocolonic
side-to-side showed that Kono-S anastomosis signicantly decreased the rate of
postoperative endoscopic recurrence at 6months and presented a longer recurrencefree duration [32].
Severe inammation of ileocolonic Crohn’s disease develops mesenteric
thickening and fat wrapping. Some evidence showed ileocolic resection with the
mesentery may reduce the rate of surgical recurrence since the removal of mesentery could reduce immunological input and recruitment of broblast precursors [29, 33].
Positive resection margins, granuloma, and plexitis are associated with risk of
postoperative recurrence [34, 35, 36]. However, an expanded resection margin was
not preventative reoperation [37] and recent guidelines do not recommend extended
resection [38, 39].
Postoperative Preventive Therapy
TNFi
TNFi have been a mainstream treatment for high-risk postoperative patients with
Crohn’s disease. The rst placebo-controlled RCT which evaluated the efcacy of
postoperative iniximab demonstrated that the iniximab group had a signicantly
lower rate of endoscopic recurrence than the placebo group at one year [40].
Covering the limitation of small number of participants, the largest RCT which
enrolled higher-risk populations with at least one of the following factors dened as
short disease duration (<10years), penetrating phenotype, history of perianal stulae, or smoking history, revealed signicantly lower postoperative endoscopic
recurrence at week 76in iniximab treated patients [9].
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