CLINICAL PRACTICE GUIDELINES

The American Society of Colon and Rectal

Surgeons Clinical Practice Guidelines for the
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Surgical Management of Ulcerative Colitis

Stefan D. Holubar, M.D.1 • Amy L. Lightner, M.D.1 • Vitaliy Poylin, M.D.2
Jon D. Vogel, M.D.3 • Wolfgang Gaertner, M.D.4 • Bradley Davis, M.D.5
Kurt G. Davis, M.D.6 • Uma Mahadevan, M.D.7 • Samir A. Shah, M.D.8
Sunanda V. Kane, M.D.9 • Scott R. Steele, M.D., M.B.A.1
Ian M. Paquette, M.D.10 • Daniel L. Feingold, M.D.11
Prepared on behalf of the Clinical Practice Guidelines Committee of the American Society of Colon and Rectal Surgeons
1 Department of Colorectal Surgery, Cleveland Clinic, Cleveland, Ohio
2 McGaw Medical Center of Northwestern University, Chicago, Illinois
3 Colorectal Surgery Section, University of Colorado Anschutz Medical Campus, Aurora, Colorado
4 Division of Colon and Rectal Surgery, Department of Surgery, University of Minnesota, Minneapolis, Minnesota
5 Colon and Rectal Surgery, Carolinas Medical Center, Charlotte, North Carolina
6 LSU College of Medicine, New Orleans, Louisiana
7 Department of Medicine, University of California, San Francisco, California
8 Department of Medicine, Brown University, Providence, Rhode Island
9 Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
10 Division of Colon and Rectal Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio
11 Section of Colorectal Surgery, Rutgers University, New Brunswick, New Jersey

T
he American Society of Colon and Rectal Surgeons and rectal surgery. This committee was created to lead
(ASCRS) is dedicated to ensuring high-quality international efforts in defining quality care for conditions
patient care by advancing the science, prevention, related to the colon, rectum, and anus and develop clini-
and management of disorders and diseases of the colon, rec- cal practice guidelines based on the best available evidence.
tum, and anus. The Clinical Practice Guidelines Committee While not proscriptive, these guidelines provide informa-
is composed of society members who are chosen because tion on which decisions can be made and do not dictate a
they have demonstrated expertise in the specialty of colon specific form of treatment. These guidelines are intended for
the use of all practitioners, health care workers, and patients
who desire information about the management of the con-
Earn Continuing Education (CME) credit online at cme.lww.com. This
activity has been approved for AMA PRA Category 1 credits.TM ditions addressed by the topics covered in these guidelines.
These guidelines should not be deemed inclusive of all
Supplemental digital content is available for this article. Direct URL cita- proper methods of care nor exclusive of methods of care
tions appear in the printed text, and links to the digital files are provided reasonably directed toward obtaining the same results.
in the HTML and PDF versions of this article on the journal’s Web site
(www.dcrjournal.com).
The ultimate judgment regarding the propriety of any spe-
cific procedure must be made by the physician considering
Funding/Support: None reported. all the circumstances presented by the individual patient.

Financial Disclosures: None reported.

STATEMENT OF THE PROBLEM
Stefan D. Holubar and Amy L. Lightner contributed equally to this arti-
cle and are co-first authors. Ulcerative colitis (UC) is an idiopathic chronic inflamma-
tory condition that affects the mucosa lining the colon and
Correspondence: Daniel L. Feingold, M.D., Professor and Chair, rectum that, for unknown reasons, continues to increase
Section of Colorectal Surgery, Rutgers University, 125 Patterson St, New in incidence with nearly 3.1 million people affected in the
Brunswick, NJ 08901. E-mail: [email protected].
United States alone.1 Patients most often present in 2 gen-
Dis Colon Rectum 2021; 64: 783–804
eral age categories, between about ages 15 and 30 or 55 and
DOI: 10.1097/DCR.0000000000002037 65, with rectal bleeding, urgency, and/or tenesmus from
© The ASCRS 2021 proctitis.2,3 The degree of symptomatology is variable over
DISEASES OF THE COLON & RECTUM VOLUME 64: 7 (2021) 783

Copyright © The American Society of Colon & Rectal Surgeons, Inc. Unauthorized reproduction of this article is prohibited.
 784 Holubar et al: Surgical Management of Ulcerative Colitis

a patient’s lifetime, and patients often exhibit a remitting placed on prospective trials, meta-analyses, systematic
and relapsing phenotype at various points during their reviews, and practice guidelines.16,17 Peer-reviewed obser-
course. Although patients can achieve mucosal healing by vational studies and retrospective studies were included
using an ever-expanding repertoire of immunoregulatory when higher-quality evidence was insufficient. Of the
medications, approximately 15% to 20% of patients with 1232 full-text manuscripts reviewed, 296 references were
UC still require colectomy for medically refractory disease included in the final manuscript (Fig. 1). The final source
and/or neoplasia of the colon or rectum.4–8 material used was evaluated for methodological quality,
Regardless of the indication for surgical intervention, the evidence base was examined, and a treatment guide-
complete removal of all at-risk tissue (ie, the colon and the line was formulated. The final grade of recommendation
rectum) is considered curative for the intestinal manifesta- was designated using the Grades of Recommendation,
tions of UC. Depending on the clinical scenario, operative Assessment, Development, and Evaluation (GRADE) sys-
strategies for patients with UC may include a total abdomi- tem (Table 1).18 When there was disagreement regarding
nal colectomy with end ileostomy or ileoproctostomy or the evidence base or treatment guideline, consensus from
total proctocolectomy with a permanent end ileostomy, the committee chair, vice chair, and 2 assigned reviewers
a continent ileostomy, or construction of an IPAA, all of determined the outcome. Members of the ASCRS Clinical
which are increasingly performed using minimally invasive Practice Guidelines Committee worked in joint produc-
techniques.7–10 This guideline focuses on the surgical man- tion of these guidelines from inception to final publica-
agement of medically refractory UC and UC-associated tion. Recommendations formulated by the subcommittee
colorectal neoplasia, key technical aspects of operative inter- were reviewed by the entire Clinical Practice Guidelines
vention, postoperative considerations specific to patients Committee, selected members of the ASCRS Inflammatory
with UC, and emerging concepts in UC that warrant further Bowel Disease committee, and selected practicing gastro-
exploration and consideration. Because the optimal man- enterologists. Consideration was given to align recommen-
agement of patients with UC involves a multidisciplinary dations with the 2020 ASCRS Clinical Practice Guidelines
team approach, including colorectal surgeons, gastroenter- for the Surgical Management of Crohn’s Disease because
ologists, radiologists, pathologists, nutritionists, and enter- there was significant overlap in the evidence base support-
ostomal therapists, these guidelines should be viewed in ing these 2 guidelines.19 The final guideline was approved
that context and represent only a portion of the treatment by the ASCRS Executive Council and peer reviewed by
paradigm utilized when caring for patients with UC. Diseases of the Colon & Rectum. In general, each ASCRS
Clinical Practice Guideline is updated every 5 years. No
METHODOLOGY funding was received for preparing this guideline and
the authors have declared no competing interests related
This guideline was written as an update to the ASCRS this material. This guideline conforms to the Appraisal of
Practice Parameters for the Surgical Treatment of Ulcerative Guidelines Research and Evaluation (AGREE) checklist.
Colitis published in 2014.11 Although bowel preparation,
enhanced recovery pathways, ostomy care, and preven-
tion of thromboembolic disease are relevant to the sur- MEDICALLY REFRACTORY ULCERATIVE COLITIS
gical management of patients with UC, these topics are
1. A multidisciplinary approach including early surgi-
addressed in other ASCRS clinical practice guidelines and
cal consultation should be used to guide optimal care
are beyond the scope of this guideline.12–15 An organized
in hospitalized patients with moderate-to-severe UC
search of MEDLINE, PubMed, EMBASE, Scopus, and the
undergoing escalation of medical therapy. Grade of
Cochrane Database of Collected Reviews limited to the
recommendation: Strong recommendation based on
English language was performed between January 1, 1995
low-quality evidence, 1C.
and December 18, 2020.11 The complete search strategy is
listed in Supplemental Digital Content http://links.lww. The goal for treating UC is to resolve symptoms and
com/DCR/B558. Keyword combinations included “ulcer- achieve mucosal healing, defined as the resolution
ative colitis,” “indeterminate colitis,” “inflammatory bowel of inflammatory changes on endoscopic evaluation.
disease,” “Crohn’s disease,” “surgery,” “colectomy,” “procto- Determining the extent and severity of disease is critical
colectomy,” “ileostomy,” “laparoscopic,” “robotic,” “Kock to selecting appropriate medical management. The extent
pouch,” “mucosectomy,” “ileoproctostomy,” and “ileal of disease should be characterized anatomically (eg, the
pouch-anal anastomosis.” Directed searches using embed- Montreal classification designates proctitis as E1, left-
ded references from primary articles were performed in sided colitis as E2, and extensive colitis as E3).20,21 Disease
selected circumstances. severity is commonly classified according to the Truelove
After removal of duplicate references, a total of 8661 and Witts criteria but may also be classified according to
unique journal titles were identified. A total of 1232 titles the Seo Index, Rachmilewitz Index, Simple Clinical Colitis
were selected for manuscript review with an emphasis Activity Index, or the Mayo Score.22–28 The 2019 American

Copyright © The American Society of Colon & Rectal Surgeons, Inc. Unauthorized reproduction of this article is prohibited.
 DISEASES OF THE COLON & RECTUM VOLUME 64: 7 (2021) 785

Key word combinations included “ulcerative colitis”, “indeterminate colitis”, or “inflammatory bowel
Additional records identified
Identification

disease”, “Crohn’s disease”, “surgery”, “colectomy”, “proctocolectomy”, “ileostomy”, “laparoscopic”,

“robotic”, “Kock pouch”, “mucosectomy”, “ileoproctostomy”, and “ileal pouch-anal anastomosis”. through other sources
Databases: MEDLINE, PubMed, EMBASE, Scopus, and the Cochrane Database of Collected Reviews (n = 212)
Dates included: January 1, 1995 through December 18, 2020
Language: English

Total records after duplicates removed

Screening

(n = 8449)

Records excluded (n = 7429)

Records screened
• Irrelevant/unrelated (n = 7202)
(n = 8661)
Eligibility

• Wrong population/other (n= 227)

Records excluded (n = 936)

• Higher quality available (n = 563)
Articles & abstracts assessed for eligibility • Irrelevant/unrelated (n = 243)
(n = 1232) • Wrong study design (n = 79)
• Not human/adult (n = 30)
• Wrong population/other (n= 21)
Included

Studies referenced in final manuscript

(n = 296)

FIGURE 1. PRISMA literature search flow sheet.

College of Gastroenterology guidelines proposed using a In hospitalized patients with a UC flare, intravenous
modified and more comprehensive version of the Truelove methylprednisolone 40 to 60 mg daily is typically recom-
and Witts criteria that incorporated inflammatory mark- mended as first-line therapy.1 In general, these patients
ers including fecal calprotectin and endoscopic disease should be continued on a diet, as tolerated, because bowel
assessment.1 When patients clinically deteriorate or have rest while on intravenous corticosteroids has shown no
increased endoscopic disease severity, escalation of medi- added benefit in 2 randomized, controlled trials,33,34 pro-
cal therapy may be needed, and utilizing a disease sever- phylaxis against thromboembolism should be initiated,
ity index allows for serial evaluations over time and can and plain films should be obtained, as needed, to assess
facilitate evolving treatment approaches. Outpatient man- for toxic megacolon. Meanwhile, patients under these
agement of UC in conjunction with gastroenterology is circumstances typically undergo endoscopy to assess
beyond the scope of this guideline but is reviewed in other disease severity and are tested for cytomegalovirus and
guidelines.1,29 Clostridioides difficile. Patients with UC receiving medical
In the in-patient setting, it can be difficult to predict therapy in this setting are monitored for signs of a clini-
which patients should continue with escalation of medical cal response, including decreased stool frequency and
therapy and which should undergo surgical intervention. hematochezia, a downward trend in serum C-reactive
Individualized assessment and decision making under protein, and a general improvement in their overall con-
these circumstances should take into account patient- dition.35,36 More recently, fecal calprotectin has been used
specific preferences, previous medical therapy including to monitor disease activity and has gained acceptance as
exposure to monoclonal antibodies, and concomitant risk a surrogate for mucosal healing.1 If there is insufficient
factors for requiring a total abdominal colectomy includ- improvement in the 3 to 5 days after initiation of cortico-
ing age at diagnosis of less than 40 years, extensive coli- steroids, intravenous infliximab at a dose of 5 to 10 mg/
tis, severe endoscopic disease with spontaneous bleeding kg or intravenous cyclosporine is typically considered as
and deep ulcerations, previous hospitalization for colitis, “rescue therapy.”1 Both infliximab and cyclosporine have
elevated C-reactive protein or erythrocyte sedimentation a mean response time of approximately 5 to 7 days in
rate, and low serum albumin.30–32 randomized, controlled trials; close observation during

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 786 Holubar et al: Surgical Management of Ulcerative Colitis

TABLE 1. The GRADE System: grading recommendations

Description Benefit versus risk and burdens Methodologic quality of supporting evidence Implications
1A Strong recommendation, Benefits clearly outweigh risk RCTs without important limitations Strong recommendation, can
High-quality evidence and burdens or vice versa or overwhelming evidence from apply to most patients in
observational studies most circumstances without
reservation
1B Strong recommendation, Benefits clearly outweigh risk RCTs with important limitations (inconsistent Strong recommendation, can
Moderate-quality evidence and burdens or vice versa results, methodologic flaws, indirect apply to most patients in
or imprecise) or exceptionally strong most circumstances without
evidence from observational studies reservation
1C Strong recommendation, Benefits clearly outweigh risk Observational studies or case series Strong recommendation but
Low- or very-low-quality and burdens or vice versa may change when higher-
evidence quality evidence becomes
available
2A Weak recommendation, Benefits closely balanced with RCTs without important limitations Weak recommendation, best
High-quality evidence risks and burdens or overwhelming evidence from action may differ depending
observational studies on circumstances or
patients’ or societal values
2B Weak recommendations, Benefits closely balanced with RCTs with important limitations (inconsistent Weak recommendation, best
Moderate-quality evidence risks and burdens results, methodologic flaws, indirect, action may differ depending
or imprecise) or exceptionally strong on circumstances or
evidence from observational studies patients’ or societal values
2C Weak recommendation, Uncertainty in the estimates of Observational studies or case series Very weak recommendations;
Low- or very-low-quality benefits, risks, and burden; other alternatives may be
evidence benefits, risk, and burden equally reasonable
may be closely balanced
GRADE = Grades of Recommendation, Assessment, Development, and Evaluation; RCT = randomized controlled trial.
Adapted from Guyatt G, Gutermen D, Baumann MH, et al. Grading strength of recommendations and quality of evidence in clinical guidelines: report from an American
College of Chest Physicians Task Force. Chest. 2006;129:174–181.18 Used with permission.

this initial 7-day treatment window is typically recom- Prolonged nonoperative care of these patients can
mended with colectomy reserved for patients who do not exhaust their physiological reserve and risks increased
respond appropriately or clinically worsen during this morbidity including colonic perforation.45,47 Other bio-
interval.27,35–38 A review of standard versus intensive inf- logics (eg, vedolizumab, ustekinumab) and the janus
liximab dosing under these circumstances is beyond the kinase (JAK) inhibitor, tofacitinib, have not yet been
scope of this guideline. adequately evaluated in acute, severe UC requiring hos-
In patients whose condition plateaus after a period pitalization; however, small case series regarding tofaci-
of initial improvement, the need and timing for colec- tinib and ustekinumab support their use under these
tomy may be difficult to judge. Second-line infliximab circumstances.48,49
or cyclosporine therapy in corticosteroid nonresponders When escalating the medical care of hospitalized
avoids colectomy in 60% to 80% of patients up to 3 patients with UC, early surgical consultation should be
months after the acute episode and in greater than 60% considered to optimize patient education and position
of patients up to 5 years after the acute episode; however, surgery as a relevant treatment option when there has
those who avoid a colectomy at their index admission been an insufficient response to the escalation of medi-
have a high risk of requiring a future colectomy.37,39–43 cal therapy. This approach also allows for the longitudi-
In patients treated with a third-line “rescue” therapy nal surgical evaluation of a patient’s clinical course and
(eg, cyclosporine for infliximab nonresponders or inf- ongoing discussion and coordination with the treating
liximab for cyclosporine nonresponders) colectomy- gastroenterology team. Consensus statements recom-
free rates may approach 70% at 3 months and 40% to mend surgical consultation for hospitalized patients with
60% at 1 year after the acute episode.44,45 However, the UC who do not show signs of improvement within 72
potential risks of using a third-line therapy can be con- hours of initiating intravenous corticosteroids or res-
siderable; a systematic review documented that adverse cue therapy, because early operative intervention has
events, serious infection, and death occurred in 23%, been associated with decreased postcolectomy compli-
7%, and 1% of patients treated with this approach.46 In cations.35,36,50–53 Additional considerations include early
particular, persistent colonic distention under these cir- involvement of an enterostomal therapist to facilitate
cumstances characterizes a subgroup of patients who stoma education, establish perioperative ostomy care,
typically respond poorly to further medical therapy and appropriately mark the anticipated stoma location, and
are at increased risk for developing toxic megacolon. alleviate patients’ anxiety.45,54

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 DISEASES OF THE COLON & RECTUM VOLUME 64: 7 (2021) 787

2. Patients with severe medically refractory UC, fulmi- that predisposes to increased risk is not well defined.72,73
nant colitis, toxic megacolon, or colonic perforation Recognizing this risk, patients maintained on high-dose
should typically undergo total abdominal colectomy corticosteroids should typically undergo total abdominal
with end ileostomy. Grade of recommendation: Strong colectomy and end ileostomy as their initial stage rather
recommendation based on low-quality evidence, 1C. than a total proctocolectomy with IPAA to reduce the risk
Acutely worsening patients are at risk for developing ful- of anastomotic leak and pelvic sepsis, the leading causes
minant colitis or toxic megacolon. Fulminant colitis repre- of pouch failure.74–77 After a staged total abdominal colec-
sents a severe form of acute colitis that may involve more tomy, proctectomy with IPAA should typically be delayed
than 10 bloody stools per day, bleeding, a blood trans- until corticosteroids have been weaned because of the
fusion requirement, an erythrocyte sedimentation rate increased risk of anastomotic leak and pelvic sepsis related
>30 mm/h, fever, tachycardia, and abdominal pain and to these medications.77
distension.36,55 Radiographic findings under these circum- Meanwhile, immunomodulators (eg, 6-mercaptupu-
stances can include colonic dilation and a thick, edema- rine, azathioprine, and methotrexate), originally used as
tous colon wall with thumb printing.36,56 Meanwhile, toxic monotherapy for maintenance of remission before the
megacolon, an extreme form of colitis, is usually associated era of biologic therapy and now used in conjunction with
with a thin colon wall and total or segmental colonic dila- biologics to reduce immunogenicity primarily associated
tion (diameter ≥5.5 cm) without a mechanical obstruction with anti-tumor necrosis factor (TNF) agents, have not
but with systemic toxicity.57 been associated with increased postoperative complica-
In practice, in the setting of severe, medically refrac- tions according to single-center series and systematic
tory UC, fulminant colitis, or toxic megacolon, clinical reviews.78–83 The decision to perform a proctocolectomy
deterioration and typical signs of impending or contained and IPAA in a staged fashion should not typically be influ-
(ie, sealed) perforation or peritonitis may be masked by enced by immunomodulator exposure.
ongoing immunosuppressive medical therapy.58,59 In a The relationship between monoclonal antibody ther-
retrospective study of 89 patients who have IBD with apy and adverse postoperative outcomes in the setting of
fulminant colitis (n = 72; 81%) and toxic colitis (n = 17; UC remains controversial.82–89 Most studies show no signif-
19%) who required colectomy, 14 (16%) had a colon per- icant association between the use of preoperative anti-TNF
foration identified either immediately before or during therapy and postoperative complications.86,87,90–97 However,
surgery, most often in the cecum or distal third of the the 2 largest, single-center series evaluating preoperative
transverse colon.55 Given that mortality rates increase exposure to anti-TNF therapy at the time of IPAA showed
with longer intervals between colonic perforation and sur- significantly increased rates of anastomotic leak and pelvic
gical intervention, especially in the setting of multisystem sepsis with anti-TNF exposure.86,87 Similarly, the largest,
organ failure, fulminant colitis or toxic megacolon should relevant meta-analysis of patients with UC showed a sig-
prompt urgent total abdominal colectomy with end ileos- nificantly increased risk of both early complications after
tomy.58,60–64 A proctectomy is usually avoided under these IPAA (OR, 4.12; 95% CI, 2.37–7.15) and late (postileos-
circumstances,65,66 and, given the concerns for developing tomy closure) complications (OR, 2.27; 95% CI, 1.27–4.05)
a rectal stump dehiscence, a variety of maneuvers can be in patients exposed to anti-TNF therapy before undergo-
utilized, such as implanting the rectal stump in the subcu- ing IPAA.98 In addition, a large, retrospective review using
taneous tissues, creating a mucous fistula instead of a rec- data from an insurance claims database found significantly
tal stump, or decompressing the rectal stump transanally increased rates of postoperative complications following
via a rectal tube.67 IPAA in the setting of preoperative exposure to anti-TNF
therapy.99 However, in contrast, the largest prospective
3. A staged approach for an IPAA should typically be
study to date (the PUCCINI trial presented at Digestive
considered in patients being treated with high-dose
Disease Week, San Diego, CA, in 2019) did not show any
corticosteroids or monoclonal antibodies. Grade of
association between monoclonal antibodies or their asso-
recommendation: Strong recommendation based on
ciated drug levels and adverse postoperative outcomes.100
low-quality evidence, 1C.
Likewise, a prospective study of preoperative serum anti-
Although the efficacy of corticosteroids for the treatment TNF drug levels from 94 consecutive patients with UC
of acute and refractory UC has been well established, found no association between increased serum drug levels
preoperative exposure to corticosteroids is associated and adverse outcomes after surgery.101
with adverse postoperative outcomes.28,68–71 Preoperative As with anti-TNF medications, the literature remains
high-dose corticosteroids, defined as >20 mg of pred- controversial regarding whether preoperative exposure
nisone equivalents per day, are associated with signifi- to newer classes of monoclonal antibodies or small-mol-
cantly increased postoperative infectious complications, ecule inhibitors influences postoperative outcomes. Two
although the duration of high-dose corticosteroid use single-center, retrospective series reported no significant

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 788 Holubar et al: Surgical Management of Ulcerative Colitis

increases in post-IPAA complications after preoperative for neoplasia, patients with PSC should begin screening
exposure to vedolizumab, but a multicenter, retrospective at the time of diagnosis and undergo surveillance annu-
review including both patients with UC and with Crohn’s ally. The European Crohn’s and Colitis Organization rec-
disease reported significantly increased rates of infec- ommends that the highest-risk patients, those with PSC
tious complications after abdominal operations in patients or a history of dysplasia or stricture, undergo annual
exposed to vedolizumab compared with patients exposed colonoscopy, that intermediate-risk patients with exten-
to anti-TNF medication.97,102,103 Ustekinumab, an anti- sive or long-standing colitis or a family history of CRC
interleukin approved for UC treatment in 2019, has not undergo colonoscopy every 2 to 3 years, and that low-risk
yet been studied with regard to postoperative outcomes in patients utilize a 5-year interval. Surveillance colonoscopy
patients with UC. Tofacitinib, approved for UC treatment should, ideally, be performed when the colonic disease
in 2018, has also not yet been evaluated regarding postop- is in remission.115 Meanwhile, the American Society for
erative outcomes. Recognizing the ongoing controversy, it Gastrointestinal Endoscopy recommends that patients
is possible that a staged approach to proctocolectomy and with PSC, active inflammation, a history of dysplasia or
IPAA in the setting of monoclonal antibody therapy may CRC in a first-degree relative, or an anatomic abnormality
mitigate the risk of postoperative pelvic sepsis, especially such as a stricture have annual surveillance colonoscopy
in patients with additional risk factors such as anemia, and that average-risk patients undergo surveillance colo-
poor nutrition, >10% weight loss in the 6 months before noscopy every 1 to 3 years.116,117 Of note, patients with UC
the operation, or a BMI <18 kg/m2.104 who have had a colectomy but have a rectal stump left in
situ are at risk of developing neoplasia and should undergo
regular proctoscopic surveillance, as well.118–120
ULCERATIVE COLITIS-ASSOCIATED COLORECTAL Surveillance colonoscopy for patients with UC, accord-
NEOPLASIA ing to American Society for Gastrointestinal Endoscopy
and American Gastroenterological Association guidelines,
4. Patients with UC should undergo endoscopic sur-
is typically recommended using high-definition white-
veillance at regular intervals. Chromoendoscopy or
light colonoscopy with nontargeted (ie, random) 4-quad-
high-definition white-light endoscopy is typically
rant biopsies (typically taken at 10-cm intervals with a total
recommended for optimal surveillance. Grade of rec-
of ≥32 biopsies) or using chromoendoscopy with targeted
ommendation: Strong recommendation based on mod-
biopsies.112,113,117,121 Early studies suggested that chromoen-
erate-quality evidence, 1B.
doscopy was superior to standard white-light endoscopy
Compared with age-matched controls, patients with UC for detecting adenomas with or without surrounding dys-
are at increased risk for developing colorectal cancer plasia and resulted in improved dysplasia detection with
(CRC).105 Risk factors for CRC in patients with UC include fewer overall biopsies.116,122–127 However, endoscopy with
younger age at the time of diagnosis of UC, longer duration high-definition white-light platforms has demonstrated
of disease, increased extent of disease (pancolitis carries a similar dysplasia detection during surveillance colonos-
greater risk than proctitis or left-sided disease), severity copy compared with chromoendoscopy under these cir-
of disease and inflammation (quiescent disease carries a cumstances.1,128,129 In addition, the infrastructure required
lower risk), a family history of CRC especially if diagnosed for widespread adoption of chromoendoscopy surveillance
before the age of 50, and the presence of primary scleros- may be a barrier to implementation given the increased
ing cholangitis (PSC).106 However, recent reports suggest endoscopy time and associated expenses typically related
that the risk for developing CRC in the setting of UC has to chromoendoscopy and the relatively limited technical
been decreasing over time.107 Previous reports suggested expertise available among endoscopists in practice.130 For
a 2%, 8%, and 18% cumulative risk of CRC 10, 20, and 30 these reasons, high-definition white-light colonoscopy or
years after the diagnosis of UC, whereas more recent meta- chromoendoscopy can be used for surveillance examina-
analyses report a cumulative risk of 1%, 3%, and 7%.108–110 tions depending on availability and local expertise.
Given the risk of neoplasia, surveillance colonoscopy Meanwhile, because most dysplasia under these cir-
for patients with UC is endorsed by multiple societies; cumstances is visible with high-definition colonoscopy,
however, controversy persists regarding the optimal tim- performing surveillance with random biopsies has been
ing for initiating screening and recommended surveil- called into question; the decision to perform targeted
lance intervals.111 Regardless of the extent of disease at biopsies only or to also obtain random biopsies may be
initial diagnosis, patients should undergo a screening individualized based on risk factors (eg, PSC, previous
colonoscopy within 8 years of the onset of symptoms. dysplasia found on random biopsy).1 A prospective multi-
The recommended intervals for subsequent surveillance center study of 1000 patients with IBD undergoing surveil-
endoscopic examinations are determined by individual- lance colonoscopy in France from 2009 to 2011 reported
ized risk assessment and vary by different societies’ guide- 94 patients with dysplasia. The yield of dysplasia found
lines.112–114 Recognizing their significantly increased risk by random biopsies was 0.2% (68 of 31,865 biopsies), but

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 DISEASES OF THE COLON & RECTUM VOLUME 64: 7 (2021) 789

only 12 of the 94 patients (13%) with dysplasia were diag- endoscopically.113,117 Visible dysplastic lesions with LGD
nosed by random biopsies. Of note, dysplasia found by or HGD, in colitic or noncolitic mucosa, that are amenable
random biopsies was associated with a personal history of to complete endoscopic resection (ie, dysplasia-free mar-
dysplasia, a colon with loss of compliance and folds, and gins), without invisible dysplasia in the flat mucosa imme-
PSC; therefore, this study recommended random biop- diately adjacent to the polypectomy site or elsewhere in the
sies during surveillance colonoscopies for patients with colon, should be treated with endoscopic excision when
these risk factors.131 Finally, a recent randomized, con- appropriate expertise is available.113,139–141 En bloc removal
trolled trial of 305 patients with IBD from a single center is preferred over piecemeal polypectomy to allow for his-
in Sweden undergoing surveillance colonoscopy with both tological evaluation regarding the completeness of resec-
random and targeted biopsies found that high-definition tion; this may require referral to a center experienced in
chromoendoscopy was superior to high-definition white- advanced polypectomy techniques including endoscopic
light endoscopy in terms of detecting neoplasia.132 In this mucosal resection and endoscopic submucosal dissection.
study, colonoscopies with dye-spray chromoendoscopy Although the success of endoscopic mucosal resection and
took an average of 7 minutes longer than the white-light endoscopic submucosal dissection in the setting of UC has
examinations. only been demonstrated in small studies, and the long-
term efficacy of these techniques with regard to preventing
5. Patients with visible polypoid or nonpolypoid dyspla-
subsequent neoplasia or influencing the need for surgery
sia that is completely excised endoscopically should
is unclear, these advanced approaches may facilitate com-
undergo endoscopic surveillance. Patients with visible
plete endoscopic excision with negative margins.142–144 At
dysplasia not amenable to endoscopic excision, invis-
the time of endoscopic excision, depending on the cir-
ible dysplasia in the flat mucosa surrounding a visible
cumstances, a tattoo can be placed adjacent to the polyp-
dysplastic lesion, or colorectal adenocarcinoma should
ectomy site to facilitate future surveillance, and biopsies
typically undergo total proctocolectomy with or with-
should typically be obtained of the flat mucosa surround-
out IPAA. Grade of recommendation: Strong recom-
ing the site to evaluate for adjacent invisible dysplasia.112,145
mendation based on moderate-quality evidence, 1B.
The recommendation to pursue ongoing surveillance
In patients with colitis, endoscopic biopsies may be classi- rather than total proctocolectomy for patients with UC
fied as negative for dysplasia, indefinite for dysplasia, low- who have had a visible dysplastic lesion excised endo-
grade dysplasia (LGD), or high-grade dysplasia (HGD) scopically is based on the relatively low risk of developing
based on histopathology assessment. In general, pathol- cancer while undergoing surveillance under these circum-
ogy determinations under these circumstances should be stances.146 In studies reported after 2000, the incidence of
confirmed by a second appropriately trained pathologist HGD or cancer diagnosed at surveillance colonoscopy fol-
because of high interobserver variability.112,133 Indefinite lowing the removal of a visible dysplastic lesion in patients
dysplasia is addressed in statement 6. with UC was 3% to 18% over surveillance periods of 3
Regarding the grades of dysplasia, LGD and HGD are to 7 years.136,137,147–149 In addition, a study of 30 patients
differentiated based on the distribution of nuclei within with UC who underwent endoscopic excision of a visible
the cells of the mucosa; LGD is characterized by nuclei dysplastic lesion reported that 48% had recurrent dyspla-
confined to the basal half of the cells, whereas HGD has sia, but none were found to have cancer with a mean 4.1
nuclei located haphazardly throughout the mucosa.74,78 years of follow-up.140 However, once dysplasia is identi-
The terms dysplasia-associated lesion or mass and ade- fied, patients are at a 10-fold increased risk of developing
noma-like mass have been replaced with more simplified recurrent dysplasia.138,150 Thus, close endoscopic surveil-
descriptors of visible or invisible lesions.134 Visible lesions lance with biopsies taken at the prior excision site is rec-
are described morphologically by the Paris classification as ommended within 1 to 6 months and again at 12 months
polypoid (eg, pedunculated or sessile) or nonpolypoid (eg, after removal of the index lesion.138,150 Treatment recom-
slightly elevated, flat, or depressed) and borders of lesions mendations for patients with multifocal, visible, nonpol-
are classified as distinct or indistinct.117 Retrospective ypoid dysplasia that is completely excised endoscopically
studies indicate that 64% to 92% of colorectal dysplasia warrant a multidisciplinary discussion because there is
in patients with UC is visible.135–137 Other noteworthy limited evidence to guide practice and the clinical scenar-
descriptors include ulceration and features of potential ios are often heterogeneous.
submucosal invasion such as depression and failure to lift For patients with visible dysplastic lesions not ame-
with submucosal injection that may be associated with the nable to endoscopic excision, invisible dysplasia in the
inability to resect a lesion endoscopically and raise the sus- flat mucosa surrounding visible dysplasia, multifocal
picion for cancer.138 dysplastic lesions, or confluent inflammatory pseudopol-
The management of dysplasia in patients with UC yposis interfering with the ability to adequately perform
depends on whether the dysplasia is invisible or vis- surveillance colonoscopy, total proctocolectomy is typi-
ible and whether a visible lesion is completely excised cally recommended because of the associated increased

Copyright © The American Society of Colon & Rectal Surgeons, Inc. Unauthorized reproduction of this article is prohibited.
 790 Holubar et al: Surgical Management of Ulcerative Colitis

risk of having or developing CRC.112,113,146,147 Patients with IBD with mucosal biopsies indefinite for dysplasia (92%
UC diagnosed with CRC should undergo staging and be invisible) who underwent subsequent colonoscopy iden-
discussed in a multidisciplinary team tumor board and are tified LGD in 13% of patients and HGD/CRC in 2% of
typically recommended to undergo total proctocolectomy. patients over a median follow-up period of 28 months.154
For patients undergoing total proctocolectomy under In the setting of nontargeted biopsies indefinite for dyspla-
these circumstances, an oncological resection with appro- sia, American Gastroenterological Association guidelines
priate lymph node harvest should be performed to allow recommend medical optimization to promote mucosal
for appropriate oncological staging. Patients with UC healing followed by repeat endoscopic surveillance within
diagnosed with rectal adenocarcinoma who undergo neo- 3 to 12 months using high-definition colonoscopy with
adjuvant radiotherapy should be appropriately counseled chromoendoscopy.113 Patients with indefinite dysplasia
that an IPAA in this setting may have worse functional who undergo medical therapy and do not achieve suffi-
outcomes; however, external beam radiation therapy is not cient mucosal healing or who have persistent indefinite
an absolute contraindication to subsequent pouch forma- dysplasia despite mucosal healing warrant a multidis-
tion.111 Further discussion regarding the management of ciplinary discussion, because there is limited evidence
colon cancer and rectal cancer is beyond the scope of these to guide practice and the clinical scenarios are often
guidelines. heterogeneous.
Although total proctocolectomy is most often rec-
7. Patients with invisible dysplasia should typically be
ommended to remove all at-risk tissue, selected patients
referred to an experienced endoscopist for repeat endos-
with an increased operative risk or poor functional status
copy using high-definition colonoscopy with chromo-
may benefit from a segmental colectomy depending on
endoscopy with targeted and repeat random biopsies
the degree and extent of colitis.151 In a retrospective study
within 3 to 6 months. Patients confirmed to have invis-
of 59 patients with UC with a median age of 73 years, 24
ible multifocal, low-grade dysplasia or any invisible
underwent a segmental colectomy (40% had active colitis
high-grade dysplasia should typically be considered
at operation) and 35 underwent a total proctocolectomy
for total proctocolectomy. Grade of recommendation:
(77% had active colitis at operation, p = 0.005) and, over a
Strong recommendation based on moderate-quality
median follow-up period of 7 years, no patient undergoing
evidence, 1B.
segmental colectomy developed metachronous cancer.152
In another retrospective Swedish study of 51 patients with When nontargeted biopsies reveal LGD or HGD, patients
UC who underwent segmental colectomy (n = 22) or with UC should typically undergo a high-definition
proctocolectomy (n = 29), none of the patients undergo- colonoscopy with chromoendoscopy by an experienced
ing segmental colectomy developed metachronous CRC at endoscopist.1,155 Patients who undergo repeat nontargeted
a mean follow-up of 9.4 years, although 10 patients under- biopsies in this setting and are found to have no invisible
went subsequent proctocolectomy for medically refrac- dysplasia or unifocal, invisible LGD warrant a multidis-
tory UC.153 Appropriate ongoing endoscopic surveillance ciplinary discussion because there is limited evidence to
of the retained colon and rectum is necessary when a seg- guide practice and the clinical scenarios are often hetero-
mental colectomy is performed in these highly selected geneous. If repeat nontargeted biopsies reveal multifocal
patients.118–120 LGD, total proctocolectomy is typically recommended,
although the evidence supporting this is limited. A meta-
6. Patients with visible indefinite dysplasia not amenable
analysis of 671 patients who have UC with LGD found
to endoscopic excision or invisible indefinite dysplasia
synchronous CRC in 17% of patients and a 6.1% annual
should typically undergo medical treatment to achieve
rate of dysplasia progression; risk factors for dysplasia
mucosal healing and be referred to an experienced
progression included invisible dysplasia and multifo-
endoscopist for repeat colonoscopy using high-defini-
cal LGD.146,156 The largest series of LGD, from the Dutch
tion colonoscopy with chromoendoscopy with targeted
National Pathology Registry, identified 4284 patients with
and repeat random biopsies within 3 to 12 months.
IBD (3064 with UC) with LGD between 1991 and 2010
Grade of recommendation: Strong recommendation
and found that the cumulative incidence of subsequent
based on low-quality evidence, 1C.
advanced neoplasia was 3.6%, 8.5%, 14.4%, and 21.7%
The term “indefinite dysplasia” usually applies to situa- after 1, 5, 10, and 15 years. The median time between the
tions where the pathologist cannot distinguish between diagnosis of LGD and having advanced neoplasia was 3.6
dysplastic and nondysplastic atypia because of the pres- years. In this study, although there was no stratification
ence of inflamed mucosa that can make histological inter- based on visibility or focality of lesions, repeat colonos-
pretation difficult. When indefinite dysplasia is identified copy demonstrating LGD was associated with an increased
on nontargeted (ie, random) endoscopic biopsies, up to risk of progression to CRC.157 Further supporting the rec-
28% of patients with UC will have dysplasia on subsequent ommendation for colectomy under these circumstances,
colonoscopy.113 A retrospective study of 84 patients with a single-center series of 172 patients who have UC with

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 DISEASES OF THE COLON & RECTUM VOLUME 64: 7 (2021) 791

LGD followed for a median of 48 months revealed that using a more flexible scope (eg, an upper endoscope) to
39% had advanced neoplasia at the time of colectomy.158 facilitate retroflexion within the pouch.169 Treatment of
Meanwhile, in a retrospective review of 2130 patients neoplasia diagnosed under these circumstances warrants
with UC who underwent an abdominal colectomy or a multidisciplinary discussion because there is limited evi-
total proctocolectomy, of the 141 patients who had a pre- dence to guide practice and the clinical scenarios are often
colectomy diagnosis of LGD, cancer was identified in only heterogeneous.
3 patients (2%) at the time of resection, and of the 1801
patients without a preoperative diagnosis of dysplasia,
only 62 patients (3%) were found to have dysplasia in their TECHNICAL AND POSTOPERATIVE CONSIDERATIONS
colectomy specimen.159 9. For patients with UC undergoing restorative total proc-
As with invisible LGD, the management recommen- tocolectomy with IPAA, a 2-stage, 3-stage, or modified
dations for patients with invisible HGD are based on 2-stage approach is preferred for most patients. Grade
reported rates of developing cancer that are highly vari- of recommendation: Strong recommendation based on
able. Although some series report synchronous cancer in moderate-quality evidence, 1B.
42% to 67% of patients with invisible HGD, a study of 59
patients who had UC with HGD on preoperative colonos- The number of stages involved in pouch surgery is influ-
copy revealed LGD, HGD, or cancer in 20 (34%), 3 (5%), enced by patient factors and surgeon preference.69,170 Two-
and 1 (2%) patients at the time of proctocolectomy.159 stage, 3-stage, and modified 2-stage approaches to IPAA
Furthermore, in a 2019 multicenter, retrospective study are the most common pouch operations performed.171
of 28 patients with HGD only 4 patients (14%) developed Despite the popularity of monoclonal antibody therapy
colitis-associated cancer over a median follow-up of 15 and the concern regarding IPAA formation in the setting
years.135 Regardless of the varying rates of developing CRC, of these medications, the rates of performing a 2-stage
if invisible HGD is confirmed at repeat colonoscopy using versus 3-stage IPAA have not changed significantly in the
high-definition colonoscopy with chromoendoscopy, total past decade; nearly 3 quarters of IPAAs are performed
proctocolectomy is typically recommended.112,117,138,141 with a 2-stage approach.172,173 The modified 2-stage IPAA
In practice, one should acknowledge that unaccounted (total abdominal colectomy and end ileostomy followed
variables including duration, severity, and extent of UC, by completion proctectomy and IPAA without a divert-
concomitant PSC, as well as biopsy sampling error and ing loop ileostomy), increasingly utilized in recent years,
interobserver variability among pathologists influence is not associated with increased rates of anastomotic leak,
outcomes among patients who have UC with dysplasia. It pelvic sepsis, or pouch failure compared with the conven-
is important to counsel patients about the potential risks tional 2-stage IPAA (total proctocolectomy with IPAA and
and benefits of continued endoscopic surveillance versus diverting ileostomy followed by ileostomy closure), but
total proctocolectomy in the setting of dysplasia.136,160 this technique has not been directly compared with the
3-stage approach.74,174–179
8. Endoscopic surveillance should typically be performed Meanwhile, a retrospective series of 144 patients
after IPAA. Grade of recommendation: Strong recom-
with medically refractory UC who underwent a 2-stage
mendation based on low-quality evidence, 1C.
IPAA (n = 116) or 3-stage IPAA (n = 28) over an 11-year
Retained rectal mucosa near the anal transition zone period suggested an overuse of the 3-stage approach.172 In
(ATZ) following IPAA is at risk for developing dysplasia. this study, perioperative complications were significantly
A mucosectomy with handsewn anastomosis at the time influenced by surgeon experience (high-volume surgeons
of IPAA does not eliminate this concern because retained were defined as having performed ≥50 IPAAs) and not
islands of at-risk rectal mucosa can persist following a by emergent operative status or preoperative exposure to
mucosectomy.161–163 Although the risk of dysplasia in the corticosteroids or anti-TNF therapy. The authors reported
rectal remnant/ATZ or ileal pouch is low, periodic endo- that a 2-stage IPAA was not associated with an increased
scopic evaluation should typically be performed.161,164–166 risk of anastomotic leak or pouch failure.172 Another series
Recommended surveillance intervals vary based on soci- of 212 patients with IPAA compared a 2-stage (n = 157)
etal guidelines, but a history of neoplasia in the prior with a 3-stage (n = 55) IPAA and found no differences in
proctocolectomy specimen confers the greatest risk of postoperative complications, including rates of anasto-
subsequent dysplasia and warrants increased frequency motic leak, pouchitis, or pouch failure. Of note, there were
of surveillance.113,121,138,167 Although examination inter- no differences in the preoperative exposure to corticoste-
vals are not universally accepted, typically, pouchoscopy roids or monoclonal antibodies between the 2 groups.173
is performed 1 year after surgery and then every 3 to 5 On the other hand, 2 multicenter studies found improved
years thereafter; for patients who had neoplasia at the time postoperative outcomes with a 3-stage approach.180–183 In
of their proctocolectomy, pouchoscopy every 1 to 3 years practice, it is important to individualize treatment in these
should be considered.168 Pouchoscopy is often performed cases and consider disease severity, preoperative exposure

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 792 Holubar et al: Surgical Management of Ulcerative Colitis

to immunomodulators, comorbidities, the presence of does not significantly affect short-term postoperative
anemia, and nutritional status in addition to intraopera- outcomes or long-term functional outcomes; however,
tive factors such as tension across the pouch anastomosis medical comorbidities and preexisting impaired func-
and surgeon preference.159 Although the preferred staged tion should be considered when counseling these patients
approach remains controversial, with the ever-expanding regarding pouch surgery.220–225 Of note, older and aging
armamentarium of immunomodulatory agents used to patients with pouch may experience worsening daytime
treat these patients, a 3-stage IPAA should typically be and nighttime bowel frequency and increased rates of fecal
considered to minimize postoperative morbidity.180,181 incontinence because the sphincter complex weakens with
Regardless of the particular staged approach utilized, age.220,222,226–229
laparoscopic or robotic approaches for IPAA are preferred Obesity, in the setting of pouch surgery, is associated
when expertise is available due to reported improved with increased operative times, blood loss, and difficulty
short-term outcomes, including shorter length of hos- in achieving sufficient mesenteric length for a tension-free
pital stay, reduced intraoperative blood loss, decreased IPAA; however, obesity is not associated with impaired
wound infection rates, improved cosmesis, and equiva- functional outcomes including incontinence, frequency
lent long-term functional outcomes and overall pouch of bowel movements, and pad usage.230–233 Preoperative
failure rates.184–190 In terms of other minimally invasive weight loss can potentially improve outcomes and per-
techniques, the recently introduced transanal approach forming a 3-stage IPAA to allow time for weight loss and
to restorative proctectomy has been shown to be safe and mesenteric lengthening (which typically occurs after cre-
feasible in early studies and has demonstrated long-term ating an end ileostomy) may be a particularly useful strat-
functional outcomes and quality-of-life scores equivalent egy in these patients.234–236
to conventional approaches in 2 multicenter comparative Total proctocolectomy with an end ileostomy, an
series.191–194 alternative to IPAA,7,8 is considered a safe, effective, and
curative operation with quality-of-life outcomes equiva-
10. Total proctocolectomy with IPAA, end ileostomy, or
lent to IPAA.237 This nonrestorative approach may be the
continent ileostomy are acceptable options for patients
preferred operative strategy in patients with fecal inconti-
with UC undergoing elective surgery. Grade of recom-
nence, inadequate access to a bathroom, anorectal disease,
mendation: Strong recommendation based on moder-
barriers to surveillance, or limited physiological reserve
ate-quality evidence, 1B.
secondary to comorbid conditions who may be at risk of
Total proctocolectomy with IPAA has become the most pouch failure or poor pouch function.8,238
commonly performed operative intervention for patients A continent ileostomy (eg, Kock pouch) is a potential
with UC and is associated with an acceptable morbidity option for highly selected patients in whom an IPAA is
rate (19%–27%), an extremely low mortality rate (<0.5%), contraindicated or has failed or in those who otherwise
and a quality of life that approaches that of the healthy prefer a permanent ileostomy over a restorative procedure.
population.195–203 When appropriate, a minimally invasive However, although continence is achieved in most patients,
approach should typically be considered because of the these reservoirs have high rates of dysfunction and of
associated reduced length of hospital stay and improved needing operative revision or excision.239–244 In a French
short-term outcomes, cosmesis, and fertility.185,187,204–214 series of 49 patients undergoing continent ileostomy
Pouch surgery often utilizes a J-type configuration because with a mean follow-up of 20.5 months, 35% experienced
of its ease of construction and relatively predictable emp- early postoperative complications and 45% developed late
tying. J pouches are associated with fewer evacuation complications requiring 50 reoperations.245 Another ret-
difficulties compared with S-type pouches (especially an rospective series of 330 patients reported 10- and 20-year
S pouch with a longer spout), but an S-pouch construc- continent ileostomy survival rates of 87% and 77%. In this
tion may be particularly useful when additional length study, at a median 11 years of follow-up, patients had, on
is needed for a tension-free IPAA.215,216 In terms of tech- average, 3.7 complications and 2.9 revisions and had a
nique, a stapled anastomosis is typically preferred over a median revision-free interval of 14 months.246
mucosectomy with handsewn anastomosis, because the In terms of another potential option for patients who
data suggest improved bowel function and symptom-spe- have UC with a failed pouch, redo pouch surgery may be
cific quality-of-life metrics with this approach.217–219 a viable alternative in certain centers. It is important to
Although restorative procedures have been popu- counsel patients regarding realistic expectations of redo
larized, an IPAA may not be suitable for all patients. pouch surgery, because these operations can be compli-
Advanced age, significant medical comorbidities, underly- cated by higher rates of pelvic sepsis and pouch failure
ing bowel dysfunction, and obesity should be considered and increased stool frequency and urgency compared
to optimize IPAA functional outcomes. Appropriately with primary pouch surgery.247–249 Further discussion
selected older patients without fecal incontinence may regarding redo pouch surgery is beyond the scope of these
safely undergo IPAA because chronological age alone guidelines.

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 DISEASES OF THE COLON & RECTUM VOLUME 64: 7 (2021) 793

11. Total abdominal colectomy with ileorectal anastomo- between patients with UC (with or without IPAA) and
sis may be considered in selected patients who have UC patients without UC.262,263 However, according to a large
with relative rectal sparing. Grade of recommendation: retrospective review of patients with UC in the Danish
Weak recommendation based on moderate-quality evi- National Patient Registry, patients with a failed IPAA had
dence, 2B. significantly lower in vitro fertilization success rates com-
pared with all other patients with UC.264
Total abdominal colectomy with an initial or staged ileo- Pregnancy after IPAA is not associated with an
rectal anastomosis (IRA) is associated with improved increased rate of maternal or fetal complications includ-
functional outcomes and higher quality-adjusted life-years ing low fetal birth weight, prolonged duration of labor,
compared with IPAA and avoids a pelvic dissection which delivery-related complications, or need for an unplanned
may preserve fertility in women.250–252 Appropriately cesarean delivery.257,265,266 Although pouch dysfunction
selected patients for this technique should have a relatively has been reported during the third trimester of preg-
spared, healthy, and compliant rectum. Patients under- nancy, this appears to be transient with function return-
going IRA should be counseled regarding the potential ing to pregestational baseline independent of the mode of
need for future medical therapy to address proctitis, rec- delivery.257,266 Meanwhile, the purported benefit of cesar-
ognizing that at 5, 10, and 20 years post-IRA, 10%, 24% ean delivery to preserve function compared with a vaginal
to 27%, and 40% of these patients undergo completion delivery remains controversial, but long-term comparative
proctectomy for medically refractory disease.253–255 In functional studies by colorectal surgeons suggest that vag-
addition, surveillance endoscopy of the retained rectum inal delivery may compromise post-IPAA function.267–269
is necessary because dysplasia and adenocarcinoma in the When patients who have a pouch plan a cesarean delivery,
retained rectum occur in 7%, 12% to 14%, and 24% and it is recommended to consider having surgical expertise
0% to 3%, 2% to 7%, and 9% of patients at 10, 20, and 25 available to assist, if necessary.270
years. Prolonged duration of UC or a personal history of In terms of other quality-of-life outcomes, early
colorectal neoplasia or PSC significantly increases the risk studies reported worse sexual function after IPAA, but
for developing neoplasia in this setting.253–255 For patients more recent literature shows no significant effects on
with IRA who develop medically refractory proctitis or sexual desire, ability to achieve orgasm, or sexual satis-
rectal neoplasia, conversion from an IRA to IPAA results faction.214,265,271–273 One questionnaire-based study even
in pouch retention rates similar to primary IPAA surgery reported an overall improvement in quality of sexual
with overall pouch survival of 94% and 92% for primary life likely because of improved overall health status after
and secondary pouches.256 IPAA.274 Men with IBD, regardless of surgery, have a higher
12. Patients with UC undergoing proctectomy should be risk of erectile dysfunction than men without IBD, but
counseled regarding possible effects on fertility, preg- IPAA surgery does not appear to significantly impair their
nancy, sexual function, and urinary function. Grade of sexual function; 10 years after IPAA, abnormal ejaculation
recommendation: Strong recommendation based on has been reported in only 3% of men.214,273–275 In women,
moderate-quality evidence, 1B. studies report worse sexual function after IPAA with
increased vaginal dryness and dyspareunia, but affected
Decreased fertility rates following proctectomy with or quality-of-life scores improve within 12 months of IPAA,
without IPAA are thought to be related to postopera- suggesting that these findings are transient.271,272 The use
tive pelvic adhesions related to the pelvic dissection that of intramesorectal proctectomy, in an effort to avoid pelvic
may cause fallopian tube occlusion.257–260 Given that total nerve injury, and laparoscopy does not confer an advan-
abdominal colectomy with an ileorectal anastomosis, and tage regarding postoperative sexual function.214,272
thus no pelvic dissection, is not usually associated with Similarly, urinary function does not appear to be sig-
decreased fertility supports this proposed underlying nificantly affected in the immediate postoperative period
mechanism of infertility.207,251 Meta-analyses of patients following IPAA.257,265 However, rates of urinary urgency,
with UC post-IPAA report increased infertility rates of frequency, and incontinence may increase over time in
26% to 63% compared to 12% to 20% in nonoperative women after IPAA.257,265
controls.207,257,261 The use of a minimally invasive approach
13. Pouchitis is common after IPAA performed in the setting
may help reduce infertility rates in this setting because
of UC and is classified according to its responsiveness to
multicenter data demonstrate that a minimally invasive
antibiotics. Grade of recommendation: Strong recom-
approach to IPAA is associated with significantly lower
mendation based on moderate-quality evidence, 1B.
rates of infertility and reduced time to conceive compared
with open IPAA.204–207 Regardless of the variable natural Pouchitis is a nonspecific inflammation of the ileal mucosa
conception rates following laparoscopic IPAA (31%–73%) of the pouch associated with diarrhea, tenesmus, pelvic
or open IPAA (>50%), there are no significant differences pain and cramping, blood in the stool, and, occasion-
in the cumulative live birth rates after in vitro fertilization ally, flu-like symptoms. Pouchitis occurs in up to 40%

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 794 Holubar et al: Surgical Management of Ulcerative Colitis

of patients with UC post-IPAA and is more common in 15. A “rescue” diverting loop ileostomy can be considered
patients exposed to anti-TNF medications pre-IPAA and in the setting of worsening, acute, severe UC to poten-
in patients with indeterminate colitis or PSC.276–278 Before tially avoid an emergent total abdominal colectomy.
treatment, the diagnosis of pouchitis should typically be Grade of recommendation: Weak recommendation
confirmed by pouchoscopy with biopsies. Endoscopic based on low-quality evidence, 2C.
findings of confluent, erythematous, friable mucosa of the
In the 1980s and 1990s, studies regarding creating a
pouch body and histology demonstrating inflammation
diverting loop ileostomy and blowhole colostomy (eg,
with a normal afferent limb and ATZ are consistent with a
Turnbull procedure) rather than performing a colectomy
diagnosis of pouchitis.
to treat severe or fulminant colitis in pregnancy reported
The most common form of pouchitis is acute, antibi-
high mortality rates of up to 70%.289,290 However, a more
otic-responsive pouchitis that typically responds within
recent retrospective study done in the era of monoclonal
24 hours to oral ciprofloxacin and metronidazole or
antibody therapy found that a “rescue” diverting loop ile-
other alternative antibiotics. Antibiotics are usually pre-
ostomy for acute, severe, medically refractory colitis was
scribed for 10 to 14 days under these circumstances.279
a potential alternative to colectomy in patients who were
Chronic pouchitis is less common and is classified as
severely immunocompromised or malnourished. This
either antibiotic dependent or antibiotic refractory.280
study of 33 patients with IBD demonstrated that a “res-
Antibiotic-dependent pouchitis may be treated with
cue” ileostomy did not increase the rate of colon salvage
a single agent continuously or with rotating antibiot-
in patients with UC and Crohn’s colitis, but was able to
ics.276 Antibiotic-refractory pouchitis typically neces-
convert an emergent colectomy to an elective colectomy,
sitates an evaluation for underlying Crohn’s disease or
thereby potentially improving outcomes.291
other inflammatory disorders of the pouch and referral
to gastroenterology for management and treatment (eg, 16. Extended postoperative venous thromboembolism pro-
monoclonal antibody therapy). For antibiotic-refractory phylaxis should be considered in patients with UC exposed
pouchitis, adalimumab did not demonstrate efficacy to tofacitinib. Grade of recommendation: Weak recom-
when studied in a randomized, controlled trial but inf- mendation based on low-quality evidence, 2C.
liximab, vedolizumab, and ustekinumab have shown
Tofacitinib was approved in 2018 by the US Food and Drug
limited efficacy in retrospective analyses and may be
Administration for the treatment of moderate to severe
considered under these circumstances.279,281–285 Patients
UC following the OCTAVE 1 and 2 phase III randomized,
who have recurrent, medically refractory pouchitis may
controlled trials which demonstrated that study patients
require intestinal diversion or pouch excision to manage
had improved induction and maintenance of endoscopic
their symptoms.286
remission compared with controls.292 With a safety profile
similar to anti-TNF therapy, the most commonly reported
POTENTIAL AREAS FOR FUTURE INVESTIGATION adverse events in the phase III clinical trials were naso-
pharyngitis, arthralgia, and headache, and less than 5% of
14. Appendectomy may decrease the need for proctocolec- patients experienced a serious, nonopportunistic infec-
tomy related to medically refractory disease. Grade of tion.293,294 However, the US Food and Drug Administration
recommendation: Weak recommendation based on issued a black box warning in July 2019 detailing increased
moderate-quality evidence, 2B. risks of venous thromboembolism and death from pulmo-
nary embolism related to tofacitinib (10 mg twice daily)
The idea that appendectomy may be beneficial in patients
in patients with rheumatoid arthritis.295 Although a ret-
with medically refractory UC has been evaluated in a
rospective analysis evaluating tofacitinib in the setting of
few studies. In a prospective study of 30 patients with
UC did not show a higher rate of thromboembolic events
medically refractory UC who were referred for proc-
than placebo, patients with UC undergoing major abdom-
tocolectomy, but who instead underwent laparoscopic
inopelvic surgery are already at increased risk of postop-
appendectomy, 9 patients (30%) had a sustained clinical
erative venous thromboembolism.13,296 Thus, patients with
response and 5 patients (17%) experienced endoscopic
UC exposed to tofacitinib preoperatively may benefit from
remission at 12 months. In this study, the degree of appen-
extended postoperative thromboprophylaxis.
diceal inflammation was significantly associated with clin-
ical and endoscopic response.287 In another prospective,
multicenter study of 28 patients with medically refractory REFERENCES
UC who underwent a laparoscopic appendectomy rather 1. Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long
than proctocolectomy, 13 patients (46%) had a clinical MD. ACG Clinical Guideline: ulcerative colitis in adults. Am J
response, 5 patients (18%) had endoscopic remission, and Gastroenterol. 2019;114:384–413.
9 patients (32%) required a colectomy or new experimen- 2. Hou JK, Kramer JR, Richardson P, Mei M, El-Serag HB. The inci-
tal medical therapy within 12 months of appendectomy.288 dence and prevalence of inflammatory bowel disease among U.S.

Copyright © The American Society of Colon & Rectal Surgeons, Inc. Unauthorized reproduction of this article is prohibited.
 DISEASES OF THE COLON & RECTUM VOLUME 64: 7 (2021) 795

veterans: a national cohort study. Inflamm Bowel Dis. 2013;19: 19. Lightner AL, Vogel JD, Carmichael JC, et al. The American
1059–1064. Society of Colon and Rectal Surgeons Clinical Practice
3. Loftus CG, Loftus EV Jr, Harmsen WS, et al. Update on the inci- Guidelines for the surgical management of Crohn’s disease. Dis
dence and prevalence of Crohn’s disease and ulcerative colitis Colon Rectum. 2020;63:1028–1052.
in Olmsted County, Minnesota, 1940-2000. Inflamm Bowel Dis. 20. Satsangi J, Silverberg MS, Vermeire S, Colombel JF. The
2007;13:254–261. Montreal classification of inflammatory bowel disease: contro-
4. Holubar SD, Pendlimari R, Loftus EV Jr, et al. Drivers of cost versies, consensus, and implications. Gut. 2006;55:749–753.
after surgical and medical therapy for chronic ulcerative colitis: 21. Silverberg MS, Satsangi J, Ahmad T, et al. Toward an inte-
a nested case-cohort study in Olmsted County, Minnesota. Dis grated clinical, molecular and serological classification of
Colon Rectum. 2012;55:1258–1265. inflammatory bowel disease: report of a Working Party of the
5. Sands BE. Fulminant colitis. J Gastrointest Surg. 2005 Montreal World Congress of Gastroenterology. Can J
2008;12:2157–2159. Gastroenterol. 2005;19(suppl A):5A–36A.
6. Cima RR. Timing and indications for colectomy in chronic ulcer- 22. de Jong MJ, Huibregtse R, Masclee AAM, Jonkers DMAE,
ative colitis: surgical consideration. Dig Dis. 2010;28:501–507. Pierik MJ. Patient-reported outcome measures for use in
7. Holubar SD, Larson DW, Dozois EJ, Pattana-Arun J, Pemberton clinical trials and clinical practice in inflammatory bowel
JH, Cima RR. Minimally invasive subtotal colectomy and ileal diseases: a systematic review. Clin Gastroenterol Hepatol.
pouch-anal anastomosis for fulminant ulcerative colitis: a rea- 2018;16:648–663.e3.
sonable approach? Dis Colon Rectum. 2009;52:187–192. 23. Rachmilewitz D. Coated mesalazine (5-aminosalicylic acid)
8. Holubar SD, Privitera A, Cima RR, Dozois EJ, Pemberton JH, versus sulphasalazine in the treatment of active ulcerative coli-
Larson DW. Minimally invasive total proctocolectomy with tis: a randomised trial. BMJ. 1989;298:82–86.
Brooke ileostomy for ulcerative colitis. Inflamm Bowel Dis. 24. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-amino-
2009;15:1337–1342. salicylic acid therapy for mildly to moderately active ulcerative
9. Goligher JC, Hoffman DC, de Dombal FT. Surgical treatment of colitis. A randomized study. N Engl J Med. 1987;317:1625–1629.
severe attacks of ulcerative colitis, with special reference to the 25. Seo M, Okada M, Yao T, Ueki M, Arima S, Okumura M. An
advantages of early operation. Br Med J. 1970;4:703–706. index of disease activity in patients with ulcerative colitis. Am J
10. Hultén L. Proctocolectomy and ileostomy to pouch surgery for Gastroenterol. 1992;87:971–976.
ulcerative colitis. World J Surg. 1998;22:335–341. 26. Walmsley RS, Ayres RC, Pounder RE, Allan RN. A simple clini-
11. Ross H, Steele SR, Varma M, et al; Standards Practice Task Force cal colitis activity index. Gut. 1998;43:29–32.
of the American Society of Colon and Rectal Surgeons. Practice 27. D’Haens G, Sandborn WJ, Feagan BG, et al. A review of activ-
parameters for the surgical treatment of ulcerative colitis. Dis ity indices and efficacy end points for clinical trials of medi-
Colon Rectum. 2014;57:5–22. cal therapy in adults with ulcerative colitis. Gastroenterology.
12. Carmichael JC, Keller DS, Baldini G, et al. Clinical Practice 2007;132:763–786.
Guidelines for enhanced recovery after colon and rectal surgery 28. Truelove SC, Witts LJ. Cortisone in ulcerative colitis; final
from the American Society of Colon and Rectal Surgeons and report on a therapeutic trial. Br Med J. 1955;2:1041–1048.
Society of American Gastrointestinal and Endoscopic Surgeons. 29. Feuerstein JD, Isaacs KL, Schneider Y, Siddique SM, Falck-Ytter
Dis Colon Rectum. 2017;60:761–784. Y, Singh S; AGA Institute Clinical Guidelines Committee. AGA
13. Fleming F, Gaertner W, Ternent CA, et al. The American Society Clinical Practice Guidelines on the management of moderate to
of Colon and Rectal Surgeons Clinical Practice Guideline for severe ulcerative colitis. Gastroenterology. 2020;158:1450–1461.
the prevention of venous thromboembolic disease in colorectal 30. Monstad I, Hovde O, Solberg IC, Moum BA. Clinical course and
surgery. Dis Colon Rectum. 2018;61:14–20. prognosis in ulcerative colitis: results from population-based
14. Hendren S, Hammond K, Glasgow SC, et al. Clinical prac- and observational studies. Ann Gastroenterol. 2014;27:95–104.
tice guidelines for ostomy surgery. Dis Colon Rectum. 31. Peyrin-Biroulet L, Panés J, Sandborn WJ, et al. Defining disease
2015;58:375–387. severity in inflammatory bowel diseases: current and future
15. Migaly J, Bafford AC, Francone TD, et al; Clinical Practice directions. Clin Gastroenterol Hepatol. 2016;14:348–354.e17.
Guidelines Committee of the American Society of Colon and 32. Solberg IC, Lygren I, Jahnsen J, et al; IBSEN Study Group.
Rectal Surgeons. The American Society of Colon and Rectal Clinical course during the first 10 years of ulcerative coli-
Surgeons Clinical Practice Guidelines for the use of bowel prep- tis: results from a population-based inception cohort (IBSEN
aration in elective colon and rectal surgery. Dis Colon Rectum. Study). Scand J Gastroenterol. 2009;44:431–440.
2019;62:3–8. 33. Dickinson RJ, Ashton MG, Axon AT, Smith RC, Yeung CK, Hill
16. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. GL. Controlled trial of intravenous hyperalimentation and total
Rayyan-a web and mobile app for systematic reviews. Syst Rev. bowel rest as an adjunct to the routine therapy of acute colitis.
2016;5:210. Gastroenterology. 1980;79:1199–1204.
17. Olofsson H, Brolund A, Hellberg C, et al. Can abstract screen- 34. McIntyre PB, Powell-Tuck J, Wood SR, et al. Controlled trial
ing workload be reduced using text mining? User experiences of bowel rest in the treatment of severe acute colitis. Gut.
of the tool Rayyan. Res Synth Methods. 2017;8:275–280. 1986;27:481–485.
18. Guyatt G, Gutterman D, Baumann MH, et al. Grading strength 35. Øresland T, Bemelman WA, Sampietro GM, et al; European
of recommendations and quality of evidence in clinical guide- Crohn’s and Colitis Organisation (ECCO). European evidence
lines: report from an american college of chest physicians task based consensus on surgery for ulcerative colitis. J Crohns
force. Chest. 2006;129:174–181. Colitis. 2015;9:4–25.

Copyright © The American Society of Colon & Rectal Surgeons, Inc. Unauthorized reproduction of this article is prohibited.
 796 Holubar et al: Surgical Management of Ulcerative Colitis

36. Bitton A, Buie D, Enns R, et al; Canadian Association of 52. Bartels SA, Gardenbroek TJ, Ubbink DT, Buskens CJ, Tanis PJ,
Gastroenterology Severe Ulcerative Colitis Consensus Group. Bemelman WA. Systematic review and meta-analysis of laparo-
Treatment of hospitalized adult patients with severe ulcerative scopic versus open colectomy with end ileostomy for non-toxic
colitis: Toronto consensus statements. Am J Gastroenterol. colitis. Br J Surg. 2013;100:726–733.
2012;107:179–194; author reply 195. 53. Randall J, Singh B, Warren BF, Travis SP, Mortensen NJ, George BD.
37. Järnerot G, Hertervig E, Friis-Liby I, et al. Infliximab as res- Delayed surgery for acute severe colitis is associated with increased
cue therapy in severe to moderately severe ulcerative colitis: risk of postoperative complications. Br J Surg. 2010;97:404–409.
a randomized, placebo-controlled study. Gastroenterology. 54. Bass EM, Del Pino A, Tan A, Pearl RK, Orsay CP, Abcarian
2005;128:1805–1811. H. Does preoperative stoma marking and education by the
38. Lichtiger S, Present DH, Kornbluth A, et al. Cyclosporine in enterostomal therapist affect outcome? Dis Colon Rectum.
severe ulcerative colitis refractory to steroid therapy. N Engl J 1997;40:440–442.
Med. 1994;330:1841–1845. 55. Stewart D, Chao A, Kodner I, Birnbaum E, Fleshman J, Dietz D.
39. Bojic D, Radojicic Z, Nedeljkovic-Protic M, Al-Ali M, Jewell DP, Subtotal colectomy for toxic and fulminant colitis in the era of
Travis SP. Long-term outcome after admission for acute severe immunosuppressive therapy. Colorectal Dis. 2009;11:184–190.
ulcerative colitis in Oxford: the 1992-1993 cohort. Inflamm 56. Jones JH, Chapman M. Definition of megacolon in colitis. Gut.
Bowel Dis. 2009;15:823–828. 1969;10:562–564.
40. Dinesen LC, Walsh AJ, Protic MN, et al. The pattern and out- 57. Sheth SG, LaMont JT. Toxic megacolon. Lancet. 1998;351:509–513.
come of acute severe colitis. J Crohns Colitis. 2010;4:431–437. 58. Greenstein AJ, Barth JA, Sachar DB, Aufses AH Jr. Free colonic
41. Moskovitz DN, Van Assche G, Maenhout B, et al. Incidence perforation without dilatation in ulcerative colitis. Am J Surg.
of colectomy during long-term follow-up after cyclosporine- 1986;152:272–275.
induced remission of severe ulcerative colitis. Clin Gastroenterol 59. Roy MA. Inflammatory bowel disease. Surg Clin North Am.
Hepatol. 2006;4:760–765. 1997;77:1419–1431.
42. Laharie D, Bourreille A, Branche J, et al; Groupe d’Etudes 60. Greenstein AJ, Sachar DB, Gibas A, et al. Outcome of toxic
Thérapeutiques des Affections Inflammatoires Digestives. dilatation in ulcerative and Crohn’s colitis. J Clin Gastroenterol.
Ciclosporin versus infliximab in patients with severe ulcerative 1985;7:137–143.
colitis refractory to intravenous steroids: a parallel, open-label 61. Heppell J, Farkouh E, Dubé S, Péloquin A, Morgan S, Bernard
randomised controlled trial. Lancet. 2012;380:1909–1915. D. Toxic megacolon. An analysis of 70 cases. Dis Colon Rectum.
43. Narula N, Marshall JK, Colombel JF, et al. Systematic review 1986;29:789–792.
and meta-analysis: infliximab or cyclosporine as rescue therapy 62. Berg DF, Bahadursingh AM, Kaminski DL, Longo WE. Acute
in patients with severe ulcerative colitis refractory to steroids. surgical emergencies in inflammatory bowel disease. Am J Surg.
Am J Gastroenterol. 2016;111:477–491. 2002;184:45–51.
44. Feuerstein JD, Akbari M, Tapper EB, Cheifetz AS. Systematic 63. St Peter SD, Abbas MA, Kelly KA. The spectrum of pneumatosis
review and meta-analysis of third-line salvage therapy with intestinalis. Arch Surg. 2003;138:68–75.
infliximab or cyclosporine in severe ulcerative colitis. Ann 64. Caprilli R, Latella G, Vernia P, Frieri G. Multiple organ dysfunc-
Gastroenterol. 2016;29:341–347. tion in ulcerative colitis. Am J Gastroenterol. 2000;95:1258–1262.
45. Person B, Ifargan R, Lachter J, Duek SD, Kluger Y, Assalia A. 65. McKenna NP, Bews KA, Mathis KL, Lightner AL, Habermann
The impact of preoperative stoma site marking on the incidence EB. Surgery during admission for an ulcerative colitis flare: should
of complications, quality of life, and patient’s independence. Dis pouch formation be considered? J Surg Res. 2019;239:216–223.
Colon Rectum. 2012;55:783–787. 66. McKenna NP, Mathis KL, Pemberton JH, Lightner AL. The impact
46. Narula N, Fine M, Colombel JF, Marshall JK, Reinisch W. of age at time of ileal pouch anal anastomosis on short and long-
Systematic review: sequential rescue therapy in severe ulcer- term outcomes in adults. Inflamm Bowel Dis. 2018;24:1857–1865.
ative colitis: do the benefits outweigh the risks? Inflamm Bowel 67. Mege D, Stellingwerf M, Germain A, et al. Management of
Dis. 2015;21:1683–1694. rectal stump during laparoscopic subtotal colectomy for IBD:
47. Latella G, Vernia P, Viscido A, et al. GI distension in severe a comparative cohort study from six referral centres. J Crohn’s
ulcerative colitis. Am J Gastroenterol. 2002;97:1169–1175. Colitis. 2020;14:1214–1221.
48. Honap S, Pavlidis P, Ray S, et al. Tofacitinib in acute severe 68. Truelove SC, Witts LJ. Cortisone in ulcerative colitis; prelimi-
ulcerative colitis-a real-world tertiary center experience. nary report on a therapeutic trial. Br Med J. 1954;2:375–378.
Inflamm Bowel Dis. 2020;26:e147–e149. 69. Subramanian V, Saxena S, Kang JY, Pollok RC. Preoperative
49. Ochsenkühn T, Tillack C, Szokodi D, Janelidze S, Schnitzler steroid use and risk of postoperative complications in patients
F. Clinical outcomes with ustekinumab as rescue treatment with inflammatory bowel disease undergoing abdominal sur-
in therapy-refractory or therapy-intolerant ulcerative colitis. gery. Am J Gastroenterol. 2008;103:2373–2381.
United European Gastroenterol J. 2020;8:91–98. 70. Ordás I, Domènech E, Mañosa M, et al; ENEIDA registry of
50. Kimura H, Kunisaki R, Tatsumi K, Koganei K, Sugita A, Endo GETECCU. Post-operative morbidity and mortality of a cohort
I. Prolonged medical therapy increases the risk of surgical com- of steroid refractory acute severe ulcerative colitis: Nationwide
plications in patients with severe ulcerative colitis. Dig Surg. multicenter study of the GETECCU ENEIDA Registry. Am J
2016;33:182–189. Gastroenterol. 2018;113:1009–1016.
51. Coakley BA, Telem D, Nguyen S, Dallas K, Divino CM. 71. Llaó J, Naves JE, Ruiz-Cerulla A, et al. Improved outcome of
Prolonged preoperative hospitalization correlates with worse acute severe ulcerative colitis while using early predictors
outcomes after colectomy for acute fulminant ulcerative colitis. of corticosteroid failure and rescue therapies. Dig Liver Dis.
Surgery. 2013;153:242–248. 2016;48:608–612.

Copyright © The American Society of Colon & Rectal Surgeons, Inc. Unauthorized reproduction of this article is prohibited.
 DISEASES OF THE COLON & RECTUM VOLUME 64: 7 (2021) 797

72. Balachandran R, Tøttrup A. Safety of proctocolectomy for 89. Abelson JS, Michelassi F, Mao J, Sedrakyan A, Yeo H. Higher
ulcerative colitis under elective and non-elective circumstances: surgical morbidity for ulcerative colitis patients in the era of
preoperative corticosteroid treatment worsens outcome. Dig biologics. Ann Surg. 2018;268:311–317.
Surg. 2015;32:251–257. 90. Coquet-Reinier B, Berdah SV, Grimaud JC, et al. Preoperative
73. Khazraei H, Bananzadeh A, Hosseini SV. Early outcome of infliximab treatment and postoperative complications after lapa-
patient with ulcerative colitis who received high dose of steroid roscopic restorative proctocolectomy with ileal pouch-anal anasto-
and underwent two staged total proctocolectomy. Adv Biomed mosis: a case-matched study. Surg Endosc. 2010;24:1866–1871.
Res. 2018;7:11. 91. Krane MK, Allaix ME, Zoccali M, et al. Preoperative infliximab
74. Kiely JM, Fazio VW, Remzi FH, Shen B, Kiran RP. Pelvic sepsis therapy does not increase morbidity and mortality after lapa-
after IPAA adversely affects function of the pouch and quality roscopic resection for inflammatory bowel disease. Dis Colon
of life. Dis Colon Rectum. 2012;55:387–392. Rectum. 2013;56:449–457.
75. MacRae HM, McLeod RS, Cohen Z, O’Connor BI, Ton EN. 92. Nørgård BM, Nielsen J, Qvist N, Gradel KO, de Muckadell
Risk factors for pelvic pouch failure. Dis Colon Rectum. OB, Kjeldsen J. Pre-operative use of anti-TNF-α agents and the
1997;40:257–262. risk of post-operative complications in patients with ulcerative
76. Ziv Y, Church JM, Fazio VW, King TM, Lavery IC. Effect of colitis - a nationwide cohort study. Aliment Pharmacol Ther.
systemic steroids on ileal pouch-anal anastomosis in patients 2012;35:1301–1309.
with ulcerative colitis. Dis Colon Rectum. 1996;39:504–508. 93. Bregnbak D, Mortensen C, Bendtsen F. Infliximab and com-
77. Ritter KA, Burke JP, Stocchi L, et al. Postoperative steroid taper plications after colectomy in patients with ulcerative colitis. J
is associated with pelvic sepsis after ileal pouch-anal anastomo- Crohns Colitis. 2012;6:281–286.
sis. Inflamm Bowel Dis. 2019;25:1383–1389. 94. Ferrante M, D’Hoore A, Vermeire S, et al. Corticosteroids but
78. Eriksson C, Rundquist S, Cao Y, Montgomery S, Halfvarson J. not infliximab increase short-term postoperative infectious
Impact of thiopurines on the natural history and surgical out- complications in patients with ulcerative colitis. Inflamm Bowel
come of ulcerative colitis: a cohort study. Gut. 2019;68:623–632. Dis. 2009;15:1062–1070.
79. Mahadevan U, Loftus EV Jr, Tremaine WJ, et al. Azathioprine 95. Gainsbury ML, Chu DI, Howard LA, et al. Preoperative infliximab
or 6-mercaptopurine before colectomy for ulcerative colitis is is not associated with an increased risk of short-term postopera-
not associated with increased postoperative complications. tive complications after restorative proctocolectomy and ileal
Inflamm Bowel Dis. 2002;8:311–316. pouch-anal anastomosis. J Gastrointest Surg. 2011;15:397–403.
80. Afzali A, Park CJ, Zhu K, et al. Preoperative use of metho- 96. Kunitake H, Hodin R, Shellito PC, Sands BE, Korzenik J,
trexate and the risk of early postoperative complications in Bordeianou L. Perioperative treatment with infliximab in
patients with inflammatory bowel disease. Inflamm Bowel Dis. patients with Crohn’s disease and ulcerative colitis is not asso-
2016;22:1887–1895. ciated with an increased rate of postoperative complications. J
81. Subramanian V, Pollok RC, Kang JY, Kumar D. Systematic Gastrointest Surg. 2008;12:1730–1736.
review of postoperative complications in patients with inflam- 97. Nørgård BM, Nielsen J, Qvist N, Gradel KO, de Muckadell
matory bowel disease treated with immunomodulators. Br J OB, Kjeldsen J. Pre-operative use of anti-TNF-α agents and the
Surg. 2006;93:793–799. risk of post-operative complications in patients with Crohn’s
82. Williet N, Pillot C, Oussalah A, et al. Incidence of and impact of disease–a nationwide cohort study. Aliment Pharmacol Ther.
medications on colectomy in newly diagnosed ulcerative colitis 2013;37:214–224.
in the era of biologics. Inflamm Bowel Dis. 2012;18:1641–1646. 98. Selvaggi F, Pellino G, Canonico S, Sciaudone G. Effect of pre-
83. Pillai N, Dusheiko M, Burnand B, Pittet V. A systematic review operative biologic drugs on complications and function after
of cost-effectiveness studies comparing conventional, biologi- restorative proctocolectomy with primary ileal pouch forma-
cal and surgical interventions for inflammatory bowel disease. tion: systematic review and meta-analysis. Inflamm Bowel Dis.
PLoS One. 2017;12:e0185500. 2015;21:79–92.
84. Costa J, Magro F, Caldeira D, Alarcão J, Sousa R, Vaz-Carneiro A. 99. Kulaylat AS, Kulaylat AN, Schaefer EW, et al. Association of
Infliximab reduces hospitalizations and surgery interventions in preoperative anti-tumor necrosis factor therapy with adverse
patients with inflammatory bowel disease: a systematic review postoperative outcomes in patients undergoing abdominal sur-
and meta-analysis. Inflamm Bowel Dis. 2013;19:2098–2110. gery for ulcerative colitis. JAMA Surg. 2017;152:e171538.
85. Moore SE, McGrail KM, Peterson S, et al. Infliximab in ulcer- 100. Cohen B, Fleshner P, Kane S, et al. 415a: anti-tumor necrosis
ative colitis: the impact of preoperative treatment on rates of factor therapy is not associated with post-operative infection:
colectomy and prescribing practices in the province of British results from prospective cohort of ulcerative colitis and Crohn’s
Columbia, Canada. Dis Colon Rectum. 2014;57:83–90. disease patients undergoing surgery to identify risk factors for
86. Mor IJ, Vogel JD, da Luz Moreira A, Shen B, Hammel J, Remzi postoperative infection I (Puccini) [Abstract]. Gastroenterology.
FH. Infliximab in ulcerative colitis is associated with an 2019;156.
increased risk of postoperative complications after restorative 101. Lau C, Dubinsky M, Melmed G, et al. The impact of preop-
proctocolectomy. Dis Colon Rectum. 2008;51:1202–1207. erative serum anti-TNFα therapy levels on early postoperative
87. Selvasekar CR, Cima RR, Larson DW, et al. Effect of infliximab outcomes in inflammatory bowel disease surgery. Ann Surg.
on short-term complications in patients undergoing operation 2015;261:487–496.
for chronic ulcerative colitis. J Am Coll Surg. 2007;204:956–962. 102. Lightner AL, Mathis KL, Tse CS, et al. Postoperative outcomes
88. Geltzeiler CB, Lu KC, Diggs BS, et al. Initial surgical manage- in vedolizumab-treated patients undergoing major abdominal
ment of ulcerative colitis in the biologic era. Dis Colon Rectum. operations for inflammatory bowel disease: retrospective mul-
2014;57:1358–1363. ticenter cohort study. Inflamm Bowel Dis. 2018;24:871–876.

Copyright © The American Society of Colon & Rectal Surgeons, Inc. Unauthorized reproduction of this article is prohibited.
 798 Holubar et al: Surgical Management of Ulcerative Colitis

103. Lightner AL, McKenna NP, Moncrief S, Pemberton JH, 118. Lutgens MW, van Oijen MG, Vleggaar FP, Siersema PD,
Raffals LE, Mathis KL. Surgical outcomes in vedolizumab- Broekman MM, Oldenburg B; Dutch Initiative on Crohn and
treated patients with ulcerative colitis. Inflamm Bowel Dis. Colitis. Risk factors for rectal stump cancer in inflammatory
2017;23:2197–2201. bowel disease. Dis Colon Rectum. 2012;55:191–196.
104. Madbouly KM, Senagore AJ, Remzi FH, Delaney CP, Waters J, 119. Munie S, Hyman N, Osler T. Fate of the rectal stump after sub-
Fazio VW. Perioperative blood transfusions increase infectious total colectomy for ulcerative colitis in the era of ileal pouch-
complications after ileoanal pouch procedures (IPAA). Int J anal anastomosis. JAMA Surg. 2013;148:408–411.
Colorectal Dis. 2006;21:807–813. 120. Ten Hove JR, Bogaerts JMK, Bak MTJ, et al. Malignant and
105. Lakatos L, Mester G, Erdelyi Z, et al. Risk factors for ulcerative nonmalignant complications of the rectal stump in patients
colitis-associated colorectal cancer in a Hungarian cohort of with inflammatory bowel disease. Inflamm Bowel Dis.
patients with ulcerative colitis: results of a population-based 2019;25:377–384.
study. Inflamm Bowel Dis. 2006;12:205–211. 121. Cairns SR, Scholefield JH, Steele RJ, et al; British Society of
106. Jess T, Loftus EV Jr, Velayos FS, et al. Incidence and prognosis Gastroenterology; Association of Coloproctology for Great
of colorectal dysplasia in inflammatory bowel disease: a popu- Britain and Ireland. Guidelines for colorectal cancer screen-
lation-based study from Olmsted County, Minnesota. Inflamm ing and surveillance in moderate and high risk groups (update
Bowel Dis. 2006;12:669–676. from 2002). Gut. 2010;59:666–689.
107. Loftus EV Jr. Epidemiology and risk factors for colorectal dys- 122. Feuerstein JD, Rakowsky S, Sattler L, et al. Meta-analysis
plasia and cancer in ulcerative colitis. Gastroenterol Clin North of dye-based chromoendoscopy compared with standard-
Am. 2006;35:517–531. and high-definition white-light endoscopy in patients with
108. Lutgens MW, van Oijen MG, van der Heijden GJ, Vleggaar inflammatory bowel disease at increased risk of colon cancer.
FP, Siersema PD, Oldenburg B. Declining risk of colorectal Gastrointest Endosc. 2019;90:186–195.e1.
cancer in inflammatory bowel disease: an updated meta-anal- 123. Marion JF, Waye JD, Israel Y, et al; Chromoendoscopy Study
ysis of population-based cohort studies. Inflamm Bowel Dis. Group at Mount Sinai School of Medicine. Chromoendoscopy
2013;19:789–799. is more effective than standard colonoscopy in detecting dys-
109. Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal can- plasia during long-term surveillance of patients with colitis.
cer in ulcerative colitis: a meta-analysis. Gut. 2001;48:526–535. Clin Gastroenterol Hepatol. 2016;14:713–719.
110. Ekbom A, Helmick C, Zack M, Adami HO. Ulcerative colitis 124. Marion JF, Waye JD, Present DH, et al; Chromoendoscopy Study
and colorectal cancer. A population-based study. N Engl J Med. Group at Mount Sinai School of Medicine. Chromoendoscopy-
1990;323:1228–1233. targeted biopsies are superior to standard colonoscopic sur-
111. Lightner AL, Spinelli A, McKenna NP, Hallemeier CL, Fleshner veillance for detecting dysplasia in inflammatory bowel disease
P. Does external beam radiation therapy to the pelvis portend patients: a prospective endoscopic trial. Am J Gastroenterol.
worse ileal pouch outcomes? An international multi-institu- 2008;103:2342–2349.
tion collaborative study. Colorectal Dis. 2019;21:219–225. 125. Rutter MD, Saunders BP, Schofield G, Forbes A, Price AB, Talbot
112. Annese V, Daperno M, Rutter MD, et al; European Crohn’s and IC. Pancolonic indigo carmine dye spraying for the detection
Colitis Organisation. European evidence based consensus for of dysplasia in ulcerative colitis. Gut. 2004;53:256–260.
endoscopy in inflammatory bowel disease. J Crohns Colitis. 126. Rutter MD, Saunders BP, Wilkinson KH, Kamm MA, Williams
2013;7:982–1018. CB, Forbes A. Most dysplasia in ulcerative colitis is visible at
113. Farraye FA, Odze RD, Eaden J, Itzkowitz SH. AGA techni- colonoscopy. Gastrointest Endosc. 2004;60:334–339.
cal review on the diagnosis and management of colorectal 127. Kiesslich R, Goetz M, Lammersdorf K, et al. Chromoscopy-
neoplasia in inflammatory bowel disease. Gastroenterology. guided endomicroscopy increases the diagnostic yield of
2010;138:746–74, 774.e1. intraepithelial neoplasia in ulcerative colitis. Gastroenterology.
114. Clarke WT, Feuerstein JD. Colorectal cancer surveillance in 2007;132:874–882.
inflammatory bowel disease: practice guidelines and recent 128. Iacucci M, Kaplan GG, Panaccione R, et al. A randomized trial
developments. World J Gastroenterol. 2019;25:4148–4157. comparing high definition colonoscopy alone with high defini-
115. Magro F, Gionchetti P, Eliakim R, et al; European Crohn’s and tion dye spraying and electronic virtual chromoendoscopy for
Colitis Organisation [ECCO]. Third European evidence-based detection of colonic neoplastic lesions during IBD surveillance
consensus on diagnosis and management of ulcerative colitis. colonoscopy. Am J Gastroenterol. 2018;113:225–234.
part 1: definitions, diagnosis, extra-intestinal manifestations, 129. Bisschops R, Bessissow T, Joseph JA, et al. Chromoendoscopy
pregnancy, cancer surveillance, surgery, and ileo-anal pouch versus narrow band imaging in UC: a prospective randomised
disorders. J Crohns Colitis. 2017;11:649–670. controlled trial. Gut. 2018;67:1087–1094.
116. Laine L, Kaltenbach T, Barkun A, McQuaid KR, Subramanian 130. Gallinger ZR, Rumman A, Murthy SK, Nguyen GC. Perspectives
V, Soetikno R; SCENIC Guideline Development Panel. on endoscopic surveillance of dysplasia in inflammatory bowel
SCENIC international consensus statement on surveillance disease: a survey of academic gastroenterologists. Endosc Int
and management of dysplasia in inflammatory bowel disease. Open. 2017;5:E974–E979.
Gastroenterology. 2015;148:639–651.e28. 131. Moussata D, Allez M, Cazals-Hatem D, et al; the GETAID. Are
117. Laine L, Kaltenbach T, Barkun A, McQuaid KR, Subramanian random biopsies still useful for the detection of neoplasia in
V, Soetikno R; SCENIC Guideline Development Panel. patients with IBD undergoing surveillance colonoscopy with
SCENIC international consensus statement on surveillance chromoendoscopy? Gut. 2018;67:616–624.
and management of dysplasia in inflammatory bowel disease. 132. Alexandersson B, Hamad Y, Andreasson A, et al. High-
Gastrointest Endosc. 2015;81:489–501.e26. definition chromoendoscopy superior to high-definition

Copyright © The American Society of Colon & Rectal Surgeons, Inc. Unauthorized reproduction of this article is prohibited.
 DISEASES OF THE COLON & RECTUM VOLUME 64: 7 (2021) 799

white-light endoscopy in surveillance of inflammatory bowel dysplasia in patients with ulcerative colitis undergoing polyp-
diseases in a randomized trial. Clin Gastroenterol Hepatol. ectomy. Inflamm Bowel Dis. 2012;18:226–235.
2020;18:2101–2107. 148. Odze RD, Farraye FA, Hecht JL, Hornick JL. Long-term fol-
133. Itzkowitz SH, Present DH; Crohn’s and Colitis Foundation of low-up after polypectomy treatment for adenoma-like dys-
America Colon Cancer in IBD Study Group. Consensus con- plastic lesions in ulcerative colitis. Clin Gastroenterol Hepatol.
ference: colorectal cancer screening and surveillance in inflam- 2004;2:534–541.
matory bowel disease. Inflamm Bowel Dis. 2005;11:314–321. 149. van Schaik FD, Mooiweer E, van der Have M, et al; Dutch
134. Chiu K, Riddell RH, Schaeffer DF. DALM, rest in peace: a Initiative on Crohn Colitis. Adenomas in patients with inflam-
pathologist’s perspective on dysplasia in inflammatory bowel matory bowel disease are associated with an increased risk of
disease in the post-DALM era. Mod Pathol. 2018;31:1180–1190. advanced neoplasia. Inflamm Bowel Dis. 2013;19:342–349.
135. Cremer A, Demetter P, De Vos M, et al; Belgian Inflammatory 150. Wanders LK, Dekker E, Pullens B, Bassett P, Travis SP, East JE.
Bowel Disease Research and Development (BIRD) Group. Risk Cancer risk after resection of polypoid dysplasia in patients
of development of more-advanced lesions in patients with with longstanding ulcerative colitis: a meta-analysis. Clin
inflammatory bowel diseases and dysplasia. Clin Gastroenterol Gastroenterol Hepatol. 2014;12:756–764.
Hepatol. 2020;18:1528–1536.e5. 151. Krugliak Cleveland N, Ollech JE, Colman RJ, et al. Efficacy
136. Goldstone R, Itzkowitz S, Harpaz N, Ullman T. Progression of and follow-up of segmental or subtotal colectomy in patients
low-grade dysplasia in ulcerative colitis: effect of colonic loca- with colitis-associated neoplasia. Clin Gastroenterol Hepatol.
tion. Gastrointest Endosc. 2011;74:1087–1093. 2019;17:205–206.
137. Navaneethan U, Jegadeesan R, Gutierrez NG, et al. Progression 152. Khan N, Cole E, Shah Y, Paulson EC. Segmental resection is a
of low-grade dysplasia to advanced neoplasia based on the loca- safe oncological alternative to total proctocolectomy in elderly
tion and morphology of dysplasia in ulcerative colitis patients patients with ulcerative colitis and malignancy. Colorectal Dis.
with extensive colitis under colonoscopic surveillance. J Crohns 2017;19:1108–1116.
Colitis. 2013;7:e684–e691. 153. Lindberg J, Stenling R, Palmqvist R, Rutegård J. Surgery for
138. American Society for Gastrointestinal Endoscopy Standards of neoplastic changes in ulcerative colitis–can limited resection
Practice Committee; Shergill AK, Lightdale JR, Bruining DH, be justified? Outcome for patients who underwent limited sur-
et al. The role of endoscopy in inflammatory bowel disease. gery. Colorectal Dis. 2006;8:551–556.
Gastrointest Endosc. 2015;81:1101–1121 e1101–1113. 154. Choi WT, Rabinovitch PS, Wang D, Westerhoff M. Outcome
139. Friedman S, Rubin PH, Bodian C, Harpaz N, Present DH. of “indefinite for dysplasia” in inflammatory bowel disease:
Screening and surveillance colonoscopy in chronic Crohn’s correlation with DNA flow cytometry and other risk factors of
colitis: results of a surveillance program spanning 25 years. colorectal cancer. Hum Pathol. 2015;46:939–947.
Clin Gastroenterol Hepatol. 2008;6:993–998. 155. Deepak P, Hanson GJ, Fletcher JG, et al. Incremental diagnostic
140. Rubin PH, Friedman S, Harpaz N, et al. Colonoscopic pol- yield of chromoendoscopy and outcomes in inflammatory bowel
ypectomy in chronic colitis: conservative management after disease patients with a history of colorectal dysplasia on white-
endoscopic resection of dysplastic polyps. Gastroenterology. light endoscopy. Gastrointest Endosc. 2016;83:1005–1012.
1999;117:1295–1300. 156. Fumery M, Pineton de Chambrun G, Stefanescu C, et al.
141. Gomollón F, Dignass A, Annese V, et al; ECCO. 3rd European Detection of dysplasia or cancer in 3.5% of patients with inflam-
evidence-based consensus on the diagnosis and management matory bowel disease and colonic strictures. Clin Gastroenterol
of Crohn’s disease 2016: part 1: diagnosis and medical manage- Hepatol. 2015;13:1770–1775.
ment. J Crohns Colitis. 2017;11:3–25. 157. de Jong ME, Kanne H, Nissen LHC, Drenth JPH, Derikx
142. Gulati S, Emmanuel A, Burt M, Dubois P, Hayee B, Haji A. LAAP, Hoentjen F. Increased risk of high-grade dysplasia
Outcomes of endoscopic resections of large laterally spread- and colorectal cancer in inflammatory bowel disease patients
ing colorectal lesions in inflammatory bowel disease: a sin- with recurrent low-grade dysplasia. Gastrointest Endosc.
gle United Kingdom center experience. Inflamm Bowel Dis. 2020;91:1334–1342.e1.
2018;24:1196–1203. 158. Choi CH, Ignjatovic-Wilson A, Askari A, et al. Low-grade
143. Kinoshita S, Uraoka T, Nishizawa T, et al. The role of colorectal dysplasia in ulcerative colitis: risk factors for developing
endoscopic submucosal dissection in patients with ulcerative high-grade dysplasia or colorectal cancer. Am J Gastroenterol.
colitis. Gastrointest Endosc. 2018;87:1079–1084. 2015;110:1461–1471.
144. Kochhar G, Steele S, Sanaka M, Gorgun E. Endoscopic submu- 159. Murphy J, Kalkbrenner KA, Pemberton JH, et al. Dysplasia in
cosal dissection for flat colonic polyps in patients with inflam- ulcerative colitis as a predictor of unsuspected synchronous
matory bowel disease, a single-center experience. Inflamm colorectal cancer. Dis Colon Rectum. 2014;57:993–998.
Bowel Dis. 2018;24:e14–e15. 160. Venkatesh PG, Jegadeesan R, Gutierrez NG, Sanaka MR,
145. Shergill AK, Farraye FA. Toward a consensus on endoscopic Navaneethan U. Natural history of low grade dysplasia in
surveillance of patients with colonic inflammatory bowel dis- patients with primary sclerosing cholangitis and ulcerative
ease. Gastrointest Endosc Clin N Am. 2014;24:469–481. colitis. J Crohns Colitis. 2013;7:968–973.
146. Fumery M, Dulai PS, Gupta S, et al. Incidence, risk factors, and 161. Kariv R, Remzi FH, Lian L, et al. Preoperative colorectal neopla-
outcomes of colorectal cancer in patients with ulcerative colitis sia increases risk for pouch neoplasia in patients with restorative
with low-grade dysplasia: a systematic review and meta-analy- proctocolectomy. Gastroenterology. 2010;139:806–12, 812.e1.
sis. Clin Gastroenterol Hepatol. 2017;15:665–674.e5. 162. Lavery IC, Sirimarco MT, Ziv Y, Fazio VW. Anal canal inflam-
147. Kisiel JB, Loftus EV Jr, Harmsen WS, Zinsmeister AR, Sandborn mation after ileal pouch-anal anastomosis. The need for treat-
WJ. Outcome of sporadic adenomas and adenoma-like ment. Dis Colon Rectum. 1995;38:803–806.

Copyright © The American Society of Colon & Rectal Surgeons, Inc. Unauthorized reproduction of this article is prohibited.
 800 Holubar et al: Surgical Management of Ulcerative Colitis

163. Remzi FH, Fazio VW, Delaney CP, et al. Dysplasia of the anal short title: outcomes after pouch leak. Int J Colorectal Dis.
transitional zone after ileal pouch-anal anastomosis: results of 2019;34:691–697.
prospective evaluation after a minimum of ten years. Dis Colon 179. Lavryk OA, Hull TL, Duraes LC, et al. Outcomes of ileal pouch-
Rectum. 2003;46:6–13. anal anastomosis without primary diverting loop ileostomy if
164. Samaan MA, Forsyth K, Segal JP, et al. Current practices in postoperative sepsis develops. Tech Coloproctol. 2018;22:37–44.
ileal pouch surveillance for patients with ulcerative colitis: 180. Mège D, Figueiredo MN, Manceau G, Maggiori L, Bouhnik Y,
a multinational, retrospective cohort study. J Crohns Colitis. Panis Y. Three-stage laparoscopic ileal pouch-anal anastomosis
2019;13:735–743. is the best approach for high-risk patients with inflammatory
165. Derikx LAAP, Nissen LHC, Smits LJT, Shen B, Hoentjen F. bowel disease: an analysis of 185 consecutive patients. J Crohns
Risk of neoplasia after colectomy in patients with inflamma- Colitis. 2016;10:898–904.
tory bowel disease: a systematic review and meta-analysis. Clin 181. Sahami S, Bartels SA, D’Hoore A, et al. A multicentre evalu-
Gastroenterol Hepatol. 2016;14:798–806.e20. ation of risk factors for anastomotic leakage after restorative
166. Derikx LA, Kievit W, Drenth JP, et al; Dutch Initiative on proctocolectomy with ileal pouch-anal anastomosis for inflam-
Crohn and Colitis. Prior colorectal neoplasia is associated with matory bowel disease. J Crohns Colitis. 2016;10:773–778.
increased risk of ileoanal pouch neoplasia in patients with 182. Nicholls RJ, Holt SD, Lubowski DZ. Restorative proctocolec-
inflammatory bowel disease. Gastroenterology. 2014;146:119– tomy with ileal reservoir. Comparison of two-stage vs. three-
28.e1. stage procedures and analysis of factors that might affect
167. Annese V, Beaugerie L, Egan L, et al; ECCO. European evi- outcome. Dis Colon Rectum. 1989;32:323–326.
dence-based consensus: inflammatory bowel disease and 183. Penna C, Daude F, Parc R, et al. Previous subtotal colectomy
malignancies. J Crohns Colitis. 2015;9:945–965. with ileostomy and sigmoidostomy improves the morbidity
168. Lightner AL, Vaidya P, Vogler S, et al. Surveillance pouchoscopy and early functional results after ileal pouch-anal anastomosis
for dysplasia: Cleveland Clinic Ileoanal Pouch Anastomosis in ulcerative colitis. Dis Colon Rectum. 1993;36:343–348.
Database. Br J Surg. 2020;107:1826–1831. 184. Baek SJ, Baik SH, Kim CW, et al. Short- and long-term outcomes
169. Shen B. Pouchitis: what every gastroenterologist needs to know. of laparoscopic surgery for intestinal Behcet’s disease: a com-
Clin Gastroenterol Hepatol. 2013;11:1538–1549. parative study with open surgery. Surg Endosc. 2016;30:99–105.
170. Gorfine SR, Gelernt IM, Bauer JJ, Harris MT, Kreel I. 185. Lavryk OA, Stocchi L, Ashburn JH, et al. Case-matched com-
Restorative proctocolectomy without diverting ileostomy. Dis parison of long-term functional and quality of life outcomes
Colon Rectum. 1995;38:188–194. following laparoscopic versus open ileal pouch-anal anastomo-
171. Bikhchandani J, Polites SF, Wagie AE, Habermann EB, Cima sis. World J Surg. 2018;42:3746–3754.
RR. National trends of 3- versus 2-stage restorative procto- 186. Lightner AL, Grass F, McKenna NP, et al. Short-term postop-
colectomy for chronic ulcerative colitis. Dis Colon Rectum. erative outcomes following robotic versus laparoscopic ileal
2015;58:199–204. pouch-anal anastomosis are equivalent. Tech Coloproctol.
172. Hicks CW, Hodin RA, Bordeianou L. Possible overuse of 2019;23:259–266.
3-stage procedures for active ulcerative colitis. JAMA Surg. 187. Sampietro GM, Colombo F, Frontali A, et al. Totally laparo-
2013;148:658–664. scopic, multi-stage, restorative proctocolectomy for inflamma-
173. Lee GC, Deery SE, Kunitake H, et al. Comparable perioperative tory bowel diseases. A prospective study on safety, efficacy and
outcomes, long-term outcomes, and quality of life in a retro- long-term results. Dig Liver Dis. 2018;50:1283–1291.
spective analysis of ulcerative colitis patients following 2-stage 188. Schiessling S, Leowardi C, Kienle P, et al. Laparoscopic versus
versus 3-stage proctocolectomy with ileal pouch-anal anasto- conventional ileoanal pouch procedure in patients under-
mosis. Int J Colorectal Dis. 2019;34:491–499. going elective restorative proctocolectomy (LapConPouch
174. Samples J, Evans K, Chaumont N, Strassle P, Sadiq T, Koruda Trial)–a randomized controlled trial. Langenbecks Arch Surg.
M. Variant two-stage ileal pouch-anal anastomosis: an innova- 2013;398:807–816.
tive and effective alternative to standard resection in ulcerative 189. Singh P, Bhangu A, Nicholls RJ, Tekkis P. A systematic review
colitis. J Am Coll Surg. 2017;224:557–563. and meta-analysis of laparoscopic vs open restorative procto-
175. Swenson BR, Hollenbeak CS, Poritz LS, Koltun WA. Modified colectomy. Colorectal Dis. 2013;15:e340–e351.
two-stage ileal pouch-anal anastomosis: equivalent out- 190. Tilney HS, Lovegrove RE, Heriot AG, et al. Comparison of
comes with less resource utilization. Dis Colon Rectum. short-term outcomes of laparoscopic vs open approaches to
2005;48:256–261. ileal pouch surgery. Int J Colorectal Dis. 2007;22:531–542.
176. Zittan E, Wong-Chong N, Ma GW, McLeod RS, Silverberg MS, 191. Chandrasinghe P, Carvello M, Wasmann K, et al. Transanal
Cohen Z. Modified two-stage ileal pouch-anal anastomosis ileal pouch-anal anastomosis for ulcerative colitis has com-
results in lower rate of anastomotic leak compared with tradi- parable long-term functional outcomes to transabdominal
tional two-stage surgery for ulcerative colitis. J Crohns Colitis. approach: a multicentre comparative study. J Crohns Colitis.
2016;10:766–772. 2020;14:726–733.
177. Chessin DB, Gorfine SR, Bub DS, Royston A, Wong D, Bauer JJ. 192. de Buck van Overstraeten A, Mark-Christensen A, Wasmann
Septic complications after restorative proctocolectomy do not KA, et al. Transanal versus transabdominal minimally inva-
impair functional outcome: long-term follow-up from a spe- sive (completion) proctectomy with ileal pouch-anal anas-
cialty center. Dis Colon Rectum. 2008;51:1312–1317. tomosis in ulcerative colitis: a comparative study. Ann Surg.
178. Widmar M, Munger JA, Mui A, et al. Diverted versus undi- 2017;266:878–883.
verted restorative proctocolectomy for chronic ulcerative 193. Leo CA, Samaranayake S, Perry-Woodford ZL, et al. Initial
colitis: an analysis of long-term outcomes after pouch leak experience of restorative proctocolectomy for ulcerative

Copyright © The American Society of Colon & Rectal Surgeons, Inc. Unauthorized reproduction of this article is prohibited.
 DISEASES OF THE COLON & RECTUM VOLUME 64: 7 (2021) 801

colitis by transanal total mesorectal rectal excision and sin- 210. Leowardi C, Hinz U, Tariverdian M, et al. Long-term outcome
gle-incision abdominal laparoscopic surgery. Colorectal Dis. 10 years or more after restorative proctocolectomy and ileal
2016;18:1162–1166. pouch-anal anastomosis in patients with ulcerative colitis.
194. Zaghiyan K, Warusavitarne J, Spinelli A, Chandrasinghe P, Di Langenbecks Arch Surg. 2010;395:49–56.
Candido F, Fleshner P. Technical variations and feasibility of 211. Boller AM, Larson DW. Laparoscopic restorative proctocolec-
transanal ileal pouch-anal anastomosis for ulcerative colitis tomy for ulcerative colitis. J Gastrointest Surg. 2007;11:3–7.
and inflammatory bowel disease unclassified across continents. 212. Larson DW, Dozois EJ, Piotrowicz K, Cima RR, Wolff BG,
Tech Coloproctol. 2018;22:867–873. Young-Fadok TM. Laparoscopic-assisted vs. open ileal pouch-
195. Fazio VW, Ziv Y, Church JM, et al. Ileal pouch-anal anasto- anal anastomosis: functional outcome in a case-matched series.
moses complications and function in 1005 patients. Ann Surg. Dis Colon Rectum. 2005;48:1845–1850.
1995;222:120–127. 213. Tsuruta M, Hasegawa H, Ishii Y, et al. Hand-assisted ver-
196. Ferrante M, Declerck S, De Hertogh G, et al. Outcome after sus conventional laparoscopic restorative proctocolectomy
proctocolectomy with ileal pouch-anal anastomosis for ulcer- for ulcerative colitis. Surg Laparosc Endosc Percutan Tech.
ative colitis. Inflamm Bowel Dis. 2008;14:20–28. 2009;19:52–56.
197. Araki Y, Ishibashi N, Ogata Y, Shirouzu K, Isomoto H. The use- 214. Larson DW, Davies MM, Dozois EJ, et al. Sexual function,
fulness of restorative laparoscopic-assisted total colectomy for body image, and quality of life after laparoscopic and open ileal
ulcerative colitis. Kurume Med J. 2001;48:99–103. pouch-anal anastomosis. Dis Colon Rectum. 2008;51:392–396.
198. Ky AJ, Sonoda T, Milsom JW. One-stage laparoscopic restor- 215. Nicholls RJ, Pezim ME. Restorative proctocolectomy with
ative proctocolectomy: an alternative to the conventional ileal reservoir for ulcerative colitis and familial adenomatous
approach? Dis Colon Rectum. 2002;45:207–210. polyposis: a comparison of three reservoir designs. Br J Surg.
199. Hasegawa H, Watanabe M, Baba H, Nishibori H, Kitajima M. 1985;72:470–474.
Laparoscopic restorative proctocolectomy for patients with ulcer- 216. Smith L, Friend WG, Medwell SJ. The superior mesenteric
ative colitis. J Laparoendosc Adv Surg Tech A. 2002;12:403–406. artery. The critical factor in the pouch pull-through procedure.
200. Pace DE, Seshadri PA, Chiasson PM, Poulin EC, Schlachta CM, Dis Colon Rectum. 1984;27:741–744.
Mamazza J. Early experience with laparoscopic ileal pouch- 217. Al-Sukhni W, McLeod RS, MacRae H, O’Connor B, Huang H,
anal anastomosis for ulcerative colitis. Surg Laparosc Endosc Cohen Z. Oncologic outcome in patients with ulcerative coli-
Percutan Tech. 2002;12:337–341. tis associated with dyplasia or cancer who underwent stapled
201. Maartense S, Dunker MS, Slors JF, Gouma DJ, Bemelman WA. or handsewn ileal pouch-anal anastomosis. Dis Colon Rectum.
Restorative proctectomy after emergency laparoscopic colec- 2010;53:1495–1500.
tomy for ulcerative colitis: a case-matched study. Colorectal Dis. 218. Kirat HT, Remzi FH, Kiran RP, Fazio VW. Comparison of out-
2004;6:254–257. comes after hand-sewn versus stapled ileal pouch-anal anas-
202. Kienle P, Z’graggen K, Schmidt J, Benner A, Weitz J, Büchler tomosis in 3,109 patients. Surgery. 2009;146:723–9; discussion
MW. Laparoscopic restorative proctocolectomy. Br J Surg. 729.
2005;92:88–93. 219. Selvaggi F, Pellino G, Canonico S, Sciaudone G. Systematic
203. Ahmed Ali U, Keus F, Heikens JT, et al. Open versus laparo- review of cuff and pouch cancer in patients with ileal
scopic (assisted) ileo pouch anal anastomosis for ulcerative pelvic pouch for ulcerative colitis. Inflamm Bowel Dis.
colitis and familial adenomatous polyposis. Cochrane Database 2014;20:1296–1308.
Syst Rev. 2009;(1):CD006267. 220. Colombo F, Sahami S, de Buck Van Overstraeten A, et al.
204. Bartels SA, D’Hoore A, Cuesta MA, Bensdorp AJ, Lucas C, Restorative proctocolectomy in elderly IBD patients: a mul-
Bemelman WA. Significantly increased pregnancy rates after ticentre comparative study on safety and efficacy. J Crohns
laparoscopic restorative proctocolectomy: a cross-sectional Colitis. 2017;11:671–679.
study. Ann Surg. 2012;256:1045–1048. 221. Shung DL, Abraham B, Sellin J, Hou JK. Medical and surgical
205. Beyer-Berjot L, Maggiori L, Birnbaum D, Lefevre JH, Berdah complications of inflammatory bowel disease in the elderly: a
S, Panis Y. A total laparoscopic approach reduces the infertility systematic review. Dig Dis Sci. 2015;60:1132–1140.
rate after ileal pouch-anal anastomosis: a 2-center study. Ann 222. Delaney CP, Dadvand B, Remzi FH, Church JM, Fazio VW.
Surg. 2013;258:275–282. Functional outcome, quality of life, and complications after
206. Gorgun E, Cengiz TB, Aytac E, et al. Does laparoscopic ileal ileal pouch-anal anastomosis in selected septuagenarians. Dis
pouch-anal anastomosis reduce infertility compared with open Colon Rectum. 2002;45:890–894.
approach? Surgery. 2019;166:670–677. 223. Page MJ, Poritz LS, Kunselman SJ, Koltun WA. Factors affect-
207. Rajaratnam SG, Eglinton TW, Hider P, Fearnhead NS. Impact of ing surgical risk in elderly patients with inflammatory bowel
ileal pouch-anal anastomosis on female fertility: meta-analysis disease. J Gastrointest Surg. 2002;6:606–613.
and systematic review. Int J Colorectal Dis. 2011;26:1365–1374. 224. Ramage L, Qiu S, Georgiou P, Tekkis P, Tan E. Functional
208. Hahnloser D, Pemberton JH, Wolff BG, Larson DR, Crownhart outcomes following ileal pouch-anal anastomosis (IPAA)
BS, Dozois RR. The effect of ageing on function and quality of life in older patients: a systematic review. Int J Colorectal Dis.
in ileal pouch patients: a single cohort experience of 409 patients 2016;31:481–492.
with chronic ulcerative colitis. Ann Surg. 2004;240:615–621. 225. Delaney CP, Fazio VW, Remzi FH, et al. Prospective, age-related
209. McIntyre PB, Pemberton JH, Wolff BG, Beart RW, Dozois analysis of surgical results, functional outcome, and quality of life
RR. Comparing functional results one year and ten years after after ileal pouch-anal anastomosis. Ann Surg. 2003;238:221–228.
ileal pouch-anal anastomosis for chronic ulcerative colitis. Dis 226. Pellino G, Sciaudone G, Candilio G, et al. Restorative proc-
Colon Rectum. 1994;37:303–307. tocolectomy with ileal pouch-anal anastomosis is safe and

Copyright © The American Society of Colon & Rectal Surgeons, Inc. Unauthorized reproduction of this article is prohibited.
 802 Holubar et al: Surgical Management of Ulcerative Colitis

effective in selected very elderly patients suffering from ulcer- a failed ileal pouch-anal anastomosis. Dis Colon Rectum.
ative colitis. Int J Surg. 2014;12(suppl 2):S56–S59. 2009;52:1409–1414.
227. Ho KS, Chang CC, Baig MK, et al. Ileal pouch anal anastomosis 245. Parc Y, Klouche M, Bennis M, Lefèvre JH, Shields C, Tiret E.
for ulcerative colitis is feasible for septuagenarians. Colorectal The continent ileostomy: an alternative to end ileostomy? Short
Dis. 2006;8:235–238. and long-term results of a single institution series. Dig Liver
228. Menees SB, Almario CV, Spiegel BMR, Chey WD. Prevalence Dis. 2011;43:779–783.
of and factors associated with fecal incontinence: results from 246. Nessar G, Fazio VW, Tekkis P, et al. Long-term outcome and
a population-based survey. Gastroenterology. 2018;154:1672– quality of life after continent ileostomy. Dis Colon Rectum.
1681.e3. 2006;49:336–344.
229. Lightner AL, Mathis KL, Dozois EJ, et al. Results at up to 30 247. Lightner AL, Shogan BD, Mathis KL, et al. Revisional and
years after ileal pouch-anal anastomosis for chronic ulcerative reconstructive surgery for failing IPAA is associated with good
colitis. Inflamm Bowel Dis. 2017;23:781–790. function and pouch salvage in highly selected patients. Dis
230. McKenna NP, Mathis KL, Khasawneh MA, et al. Obese patients Colon Rectum. 2018;61:920–930.
undergoing ileal pouch-anal anastomosis: short-and long-term 248. Pellino G, Selvaggi F. Outcomes of salvage surgery for ileal pouch
surgical outcomes. Inflamm Bowel Dis. 2017;23:2142–2146. complications and dysfunctions. the experience of a referral cen-
231. Klos CL, Safar B, Jamal N, et al. Obesity increases risk for tre and review of literature. J Crohns Colitis. 2015;9:548–557.
pouch-related complications following restorative proctocolec- 249. Remzi FH, Aytac E, Ashburn J, et al. Transabdominal redo ileal
tomy with ileal pouch-anal anastomosis (IPAA). J Gastrointest pouch surgery for failed restorative proctocolectomy: lessons
Surg. 2014;18:573–579. learned over 500 patients. Ann Surg. 2015;262:675–682.
232. Kiran RP, Remzi FH, Fazio VW, et al. Complications and func- 250. Abdalla M, Norblad R, Olsson M, et al. Anorectal function after
tional results after ileoanal pouch formation in obese patients. ileo-rectal anastomosis is better than pelvic pouch in selected
J Gastrointest Surg. 2008;12:668–674. ulcerative colitis patients. Dig Dis Sci. 2020;65:250–259.
233. McKenna NP, Mathis KL, Khasawneh M, et al. Thirty-day hos- 251. Mortier PE, Gambiez L, Karoui M, et al. Colectomy with ileo-
pital readmission after restorative proctocolectomy and ileal rectal anastomosis preserves female fertility in ulcerative coli-
pouch anal anastomosis for chronic ulcerative colitis at a high- tis. Gastroenterol Clin Biol. 2006;30:594–597.
volume center. J Gastrointest Surg. 2017;21:1859–1864. 252. de Buck van Overstraeten A, Brar MS, Khorasani S, Dossa F,
234. Wu XR, Kirat HT, Xhaja X, Hammel JP, Kiran RP, Church JM. Myrelid P. Ileorectal anastomosis versus IPAA for the surgical
The impact of mesenteric tension on pouch outcome and qual- treatment of ulcerative colitis: a Markov decision analysis. Dis
ity of life in patients undergoing restorative proctocolectomy. Colon Rectum. 2020;63:1276–1284.
Colorectal Dis. 2014;16:986–994. 253. Andersson P, Norblad R, Söderholm JD, Myrelid P. Ileorectal
235. Maruthachalam K, Kumar R, Hainsworth P. Parking the anastomosis in comparison with ileal pouch anal anastomosis
pouch: pouch salvage after anastomotic leak following restor- in reconstructive surgery for ulcerative colitis–a single institu-
ative proctocolectomy. Report of a case. Dis Colon Rectum. tion experience. J Crohns Colitis. 2014;8:582–589.
2008;51:1724–1726. 254. Ishii H, Hata K, Kishikawa J, et al. Incidence of neoplasias
236. Martel P, Majery N, Savigny B, Sezeur A, Gallot D, Malafosse and effectiveness of postoperative surveillance endoscopy for
M. Mesenteric lengthening in ileoanal pouch anastomosis for patients with ulcerative colitis: comparison of ileorectal anas-
ulcerative colitis: is high division of the superior mesenteric tomosis and ileal pouch-anal anastomosis. World J Surg Oncol.
pedicle a safe procedure? Dis Colon Rectum. 1998;41:862–866. 2016;14:75.
237. Murphy PB, Khot Z, Vogt KN, Ott M, Dubois L. Quality of life 255. Uzzan M, Kirchgesner J, Oubaya N, et al. Risk of rectal neo-
after total proctocolectomy with ileostomy or IPAA: a system- plasia after colectomy and ileorectal anastomosis for ulcerative
atic review. Dis Colon Rectum. 2015;58:899–908. colitis. J Crohns Colitis. 2017;11:930–935.
238. Jimmo B, Hyman NH. Is ileal pouch-anal anastomosis really 256. Landerholm K, Abdalla M, Myrelid P, Andersson RE. Survival of
the procedure of choice for patients with ulcerative colitis? Dis ileal pouch anal anastomosis constructed after colectomy or sec-
Colon Rectum. 1998;41:41–45. ondary to a previous ileorectal anastomosis in ulcerative colitis
239. Lepistö AH, Järvinen HJ. Durability of Kock continent ileos- patients: a population-based cohort study. Scand J Gastroenterol.
tomy. Dis Colon Rectum. 2003;46:925–928. 2017;52:531–535.
240. Wasmuth HH, Svinsås M, Tranø G, et al. Surgical load and 257. Cornish JA, Tan E, Teare J, et al. The effect of restorative proc-
long-term outcome for patients with Kock continent ileostomy. tocolectomy on sexual function, urinary function, fertility,
Colorectal Dis. 2007;9:713–717. pregnancy and delivery: a systematic review. Dis Colon Rectum.
241. Mullen P, Behrens D, Chalmers T, et al. Barnett continent intes- 2007;50:1128–1138.
tinal reservoir. Multicenter experience with an alternative to 258. Ørding Olsen K, Juul S, Berndtsson I, Oresland T, Laurberg
the Brooke ileostomy. Dis Colon Rectum. 1995;38:573–582. S. Ulcerative colitis: female fecundity before diagnosis, during
242. Aytac E, Dietz DW, Ashburn J, Remzi FH. Long-term outcomes disease, and after surgery compared with a population sample.
after continent ileostomy creation in patients with Crohn’s dis- Gastroenterology. 2002;122:15–19.
ease. Dis Colon Rectum. 2017;60:508–513. 259. Johnson P, Richard C, Ravid A, et al. Female infertility after
243. Aytac E, Ashburn J, Dietz DW. Is there still a role for continent ileal pouch-anal anastomosis for ulcerative colitis. Dis Colon
ileostomy in the surgical treatment of inflammatory bowel dis- Rectum. 2004;47:1119–1126.
ease? Inflamm Bowel Dis. 2014;20:2519–2525. 260. Gorgun E, Remzi FH, Goldberg JM, et al. Fertility is reduced
244. Lian L, Fazio VW, Remzi FH, Shen B, Dietz D, Kiran RP. after restorative proctocolectomy with ileal pouch anal anasto-
Outcomes for patients undergoing continent ileostomy after mosis: a study of 300 patients. Surgery. 2004;136:795–803.

Copyright © The American Society of Colon & Rectal Surgeons, Inc. Unauthorized reproduction of this article is prohibited.
 DISEASES OF THE COLON & RECTUM VOLUME 64: 7 (2021) 803

261. Waljee A, Waljee J, Morris AM, Higgins PD. Threefold increased 277. Bertucci Zoccali M, Hyman NH, Skowron KB, et al. Exposure
risk of infertility: a meta-analysis of infertility after ileal pouch to anti-tumor necrosis factor medications increases the inci-
anal anastomosis in ulcerative colitis. Gut. 2006;55:1575–1580. dence of pouchitis after restorative proctocolectomy in patients
262. Pabby V, Oza SS, Dodge LE, et al. In vitro fertilization is suc- with ulcerative colitis. Dis Colon Rectum. 2019;62:1344–1351.
cessful in women with ulcerative colitis and ileal pouch anal 278. Netz U, Galbraith NJ, O’Brien S, et al. Long-term outcomes fol-
anastomosis. Am J Gastroenterol. 2015;110:792–797. lowing ileal pouch-anal anastomosis in patients with indeter-
263. Pachler FR, Toft G, Bisgaard T, Laurberg S. Use and success minate colitis. Surgery. 2018;163:535–541.
of in vitro fertilization following restorative proctocolectomy 279. Nguyen N, Zhang B, Holubar SD, Pardi DS, Singh S. Treatment
and ileal pouch-anal anastomosis: a nationwide 17-year cohort and prevention of pouchitis after ileal pouch-anal anastomo-
study. J Crohn’s Colitis. 2019;13:1283–1286. sis for chronic ulcerative colitis. Cochrane Database Syst Rev.
264. Pachler FR, Bisgaard T, Mark-Christensen A, Toft G, Laurberg 2019;5:CD001176.
S. Impact on fertility after failure of restorative proctocolec- 280. McLaughlin SD, Clark SK, Tekkis PP, Ciclitira PJ, Nicholls RJ.
tomy in men and women with ulcerative colitis: a 17-year An open study of maintenance antibiotic therapy for chronic
cohort study. Dis Colon Rectum. 2020;63:816–822. antibiotic-dependent pouchitis: efficacy, complications and
265. Cornish J, Wooding K, Tan E, Nicholls RJ, Clark SK, Tekkis outcome. Colorectal Dis. 2011;13:438–444.
PP. Study of sexual, urinary, and fecal function in females 281. Herfarth HH, Long MD, Isaacs KL. Use of biologics in pouchi-
following restorative proctocolectomy. Inflamm Bowel Dis. tis: a systematic review. J Clin Gastroenterol. 2015;49:647–654.
2012;18:1601–1607. 282. Bär F, Kühbacher T, Dietrich NA, et al; German IBD Study
266. Hahnloser D, Pemberton JH, Wolff BG, et al. Pregnancy and Group. Vedolizumab in the treatment of chronic, antibiotic-
delivery before and after ileal pouch-anal anastomosis for dependent or refractory pouchitis. Aliment Pharmacol Ther.
inflammatory bowel disease: immediate and long-term conse- 2018;47:581–587.
quences and outcomes. Dis Colon Rectum. 2004;47:1127–1135. 283. Ollech JE, Rubin DT, Glick L, et al. Ustekinumab is effective for
267. Polle SW, Vlug MS, Slors JF, et al. Effect of vaginal delivery on the treatment of chronic antibiotic-refractory pouchitis. Dig
long-term pouch function. Br J Surg. 2006;93:1394–1401. Dis Sci. 2019;64:3596–3601.
268. Remzi FH, Gorgun E, Bast J, et al. Vaginal delivery after ileal 284. Weaver KN, Gregory M, Syal G, et al. Ustekinumab is effective
pouch-anal anastomosis: a word of caution. Dis Colon Rectum. for the treatment of Crohn’s disease of the pouch in a multi-
2005;48:1691–1699. center cohort. Inflamm Bowel Dis. 2019;25:767–774.
269. Bradford K, Melmed GY, Fleshner P, Silverman N, Dubinsky 285. Kjær MD, Qvist N, Nordgaard-Lassen I, Christensen LA,
MC. Significant variation in recommendation of care for Kjeldsen J. Adalimumab in the treatment of chronic pouchitis.
women of reproductive age with ulcerative colitis postileal A randomized double-blind, placebo-controlled trial. Scand J
pouch-anal anastomosis. Dig Dis Sci. 2014;59:1115–1120. Gastroenterol. 2019;54:188–193.
270. Mahadevan U, Robinson C, Bernasko N, et al. Inflammatory 286. Holubar SD, Neary P, Aiello A, et al. Ileal pouch revision vs exci-
bowel disease in pregnancy clinical care pathway: a report sion: short-term (30-day) outcomes from the National Surgical
from the American Gastroenterological Association IBD Quality Improvement Program. Colorectal Dis. 2019;21:209–218.
Parenthood Project Working Group. Gastroenterology. 287. Sahami S, Wildenberg ME, Koens L, et al. Appendectomy for
2019;156:1508–1524. therapy-refractory ulcerative colitis results in pathological
271. Davies RJ, O’Connor BI, Victor C, MacRae HM, Cohen Z, improvement of colonic inflammation: short-term results of
McLeod RS. A prospective evaluation of sexual function and the PASSION study. J Crohns Colitis. 2019;13:165–171.
quality of life after ileal pouch-anal anastomosis. Dis Colon 288. Stellingwerf ME, Sahami S, Winter DC, et al. Prospective
Rectum. 2008;51:1032–1035. cohort study of appendicectomy for treatment of therapy-
272. Kjaer MD, Laursen SB, Qvist N, Kjeldsen J, Poornoroozy PH. refractory ulcerative colitis. Br J Surg. 2019;106:1697–1704.
Sexual function and body image are similar after laparoscopy- 289. Fazio VW. Toxic megacolon in ulcerative colitis and Crohn’s
assisted and open ileal pouch-anal anastomosis. World J Surg. colitis. Clin Gastroenterol. 1980;9:389–407.
2014;38:2460–2465. 290. Ooi BS, Remzi FH, Fazio VW. Turnbull-Blowhole colostomy
273. Mantzouranis G, Fafliora E, Glanztounis G, Christodoulou for toxic ulcerative colitis in pregnancy: report of two cases. Dis
DK, Katsanos KH. Inflammatory bowel disease and sexual Colon Rectum. 2003;46:111–115.
function in male and female patients: an update on evidence in 291. Russell TA, Dawes AJ, Graham DS, Angarita SAK, Ha C, Sack
the past ten years. J Crohns Colitis. 2015;9:1160–1168. J. Rescue diverting loop ileostomy: an alternative to emergent
274. Farouk R, Pemberton JH, Wolff BG, Dozois RR, Browning S, colectomy in the setting of severe acute refractory IBD-colitis.
Larson D. Functional outcomes after ileal pouch-anal anasto- Dis Colon Rectum. 2018;61:214–220.
mosis for chronic ulcerative colitis. Ann Surg. 2000;231:919–926. 292. Bonovas S, Lytras T, Nikolopoulos G, Peyrin-Biroulet L,
275. Friedman S, Magnussen B, O’Toole A, Fedder J, Larsen MD, Danese S. Systematic review with network meta-analysis: com-
Nørgård BM. Increased use of medications for erectile dys- parative assessment of tofacitinib and biological therapies for
function in men with ulcerative colitis and Crohn’s disease moderate-to-severe ulcerative colitis. Aliment Pharmacol Ther.
compared to men without inflammatory bowel disease: a 2018;47:454–465.
nationwide cohort study. Am J Gastroenterol. 2018;113:1355. 293. Sandborn WJ, Su C, Panes J. Tofacitinib as induction and
276. Segal JP, Ding NS, Worley G, et al. Systematic review with meta- maintenance therapy for ulcerative colitis. N Engl J Med.
analysis: the management of chronic refractory pouchitis with 2017;377:496–497.
an evidence-based treatment algorithm. Aliment Pharmacol 294. Sandborn WJ, Su C, Sands BE, et al; OCTAVE Induction 1,
Ther. 2017;45:581–592. OCTAVE Induction 2, and OCTAVE Sustain Investigators.

Copyright © The American Society of Colon & Rectal Surgeons, Inc. Unauthorized reproduction of this article is prohibited.
 804 Holubar et al: Surgical Management of Ulcerative Colitis

Tofacitinib as induction and maintenance therapy for ulcer- drugs/drug-safety-and-availability/fda-approves-boxed-warn-

ative colitis. N Engl J Med. 2017;376:1723–1736. ing-about-increased-risk-blood-clots-and-death-higher-dose-
295. U.S. Food and Drug Administration. FDA approves boxed warn- arthritis-and. Accessed March 1, 2020.
ing about increased risk of blood clots and death with higher dose 296. Sandborn WJ, Panés J, Sands BE, et al. Venous thromboembolic
of arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, events in the tofacitinib ulcerative colitis clinical development
Xeljanz XR). Issued February 25, 2019. https://www.fda.gov/ programme. Aliment Pharmacol Ther. 2019;50:1068–1076.

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