The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Surgical Management of Ulcerative Colitis

The American Society of Colon and Rectal Surgeons (ASCRS) is dedicated to ensuring high-quality patient care by advancing the science, prevention, and management of disorders and diseases of the colon, rectum, and anus. The Clinical Practice Guidelines Committee is composed of society members who are chosen because they have demonstrated expertise in the specialty of colon and rectal surgery. This committee was created to lead international efforts in defining quality care for conditions related to the colon, rectum, and anus and develop clinical practice guidelines based on the best available evidence. While not proscriptive, these guidelines provide information on which decisions can be made and do not dictate a 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 conditions addressed by the topics covered in these guidelines. These guidelines should not be deemed inclusive of all proper methods of care nor exclusive of methods of care reasonably directed toward obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician considering all the circumstances presented by the individual patient. STATEMENT OF THE PROBLEM Ulcerative colitis (UC) is an idiopathic chronic inflammatory condition that affects the mucosa lining the colon and rectum that, for unknown reasons, continues to increase in incidence with nearly 3.1 million people affected in the United States alone.1 Patients most often present in 2 general age categories, between about ages 15 and 30 or 55 and 65, with rectal bleeding, urgency, and/or tenesmus from proctitis.2,3 The degree of symptomatology is variable over a patient’s lifetime, and patients often exhibit a remitting and relapsing phenotype at various points during their course. Although patients can achieve mucosal healing by using an ever-expanding repertoire of immunoregulatory medications, approximately 15% to 20% of patients with UC still require colectomy for medically refractory disease and/or neoplasia of the colon or rectum.4–8 Regardless of the indication for surgical intervention, complete removal of all at-risk tissue (ie, the colon and the rectum) is considered curative for the intestinal manifestations of UC. Depending on the clinical scenario, operative strategies for patients with UC may include a total abdominal colectomy with end ileostomy or ileoproctostomy or total proctocolectomy with a permanent end ileostomy, a continent ileostomy, or construction of an IPAA, all of which are increasingly performed using minimally invasive techniques.7–10 This guideline focuses on the surgical management of medically refractory UC and UC-associated colorectal neoplasia, key technical aspects of operative intervention, postoperative considerations specific to patients with UC, and emerging concepts in UC that warrant further exploration and consideration. Because the optimal management of patients with UC involves a multidisciplinary team approach, including colorectal surgeons, gastroenterologists, radiologists, pathologists, nutritionists, and enterostomal therapists, these guidelines should be viewed in that context and represent only a portion of the treatment paradigm utilized when caring for patients with UC. METHODOLOGY This guideline was written as an update to the ASCRS Practice Parameters for the Surgical Treatment of Ulcerative Colitis published in 2014.11 Although bowel preparation, enhanced recovery pathways, ostomy care, and prevention of thromboembolic disease are relevant to the surgical management of patients with UC, these topics are addressed in other ASCRS clinical practice guidelines and are beyond the scope of this guideline.12–15 An organized search of MEDLINE, PubMed, EMBASE, Scopus, and the Cochrane Database of Collected Reviews limited to the English language was performed between January 1, 1995 and December 18, 2020.11 The complete search strategy is listed in Supplemental Digital Content https://links.lww.com/DCR/B558. Keyword combinations included “ulcerative colitis,” “indeterminate colitis,” “inflammatory bowel disease,” “Crohn’s disease,” “surgery,” “colectomy,” “proctocolectomy,” “ileostomy,” “laparoscopic,” “robotic,” “Kock pouch,” “mucosectomy,” “ileoproctostomy,” and “ileal pouch-anal anastomosis.” Directed searches using embedded references from primary articles were performed in selected circumstances. After removal of duplicate references, a total of 8661 unique journal titles were identified. A total of 1232 titles were selected for manuscript review with an emphasis placed on prospective trials, meta-analyses, systematic reviews, and practice guidelines.16,17 Peer-reviewed observational studies and retrospective studies were included when higher-quality evidence was insufficient. Of the 1232 full-text manuscripts reviewed, 296 references were included in the final manuscript (Fig. 1). The final source material used was evaluated for methodological quality, the evidence base was examined, and a treatment guideline was formulated. The final grade of recommendation was designated using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system (Table 1).18 When there was disagreement regarding the evidence base or treatment guideline, consensus from the committee chair, vice chair, and 2 assigned reviewers determined the outcome. Members of the ASCRS Clinical Practice Guidelines Committee worked in joint production of these guidelines from inception to final publication. Recommendations formulated by the subcommittee were reviewed by the entire Clinical Practice Guidelines Committee, selected members of the ASCRS Inflammatory Bowel Disease committee, and selected practicing gastroenterologists. Consideration was given to align recommendations with the 2020 ASCRS Clinical Practice Guidelines for the Surgical Management of Crohn’s Disease because there was significant overlap in the evidence base supporting these 2 guidelines.19 The final guideline was approved by the ASCRS Executive Council and peer reviewed by Diseases of the Colon & Rectum. In general, each ASCRS Clinical Practice Guideline is updated every 5 years. No funding was received for preparing this guideline and the authors have declared no competing interests related this material. This guideline conforms to the Appraisal of Guidelines Research and Evaluation (AGREE) checklist. TABLE 1. - The GRADE System: grading recommendations Description Benefit versus risk and burdens Methodologic quality of supporting evidence Implications 1A Strong recommendation, High-quality evidence Benefits clearly outweigh risk and burdens or vice versa RCTs without important limitations or overwhelming evidence from observational studies Strong recommendation, can apply to most patients in most circumstances without reservation 1B Strong recommendation, Moderate-quality evidence Benefits clearly outweigh risk and burdens or vice versa RCTs with important limitations (inconsistent results, methodologic flaws, indirect or imprecise) or exceptionally strong evidence from observational studies Strong recommendation, can apply to most patients in most circumstances without reservation 1C Strong recommendation, Low- or very-low-quality evidence Benefits clearly outweigh risk and burdens or vice versa Observational studies or case series Strong recommendation but may change when higher-quality evidence becomes available 2A Weak recommendation, High-quality evidence Benefits closely balanced with risks and burdens RCTs without important limitations or overwhelming evidence from observational studies Weak recommendation, best action may differ depending on circumstances or patients’ or societal values 2B Weak recommendations, Moderate-quality evidence Benefits closely balanced with risks and burdens RCTs with important limitations (inconsistent results, methodologic flaws, indirect, or imprecise) or exceptionally strong evidence from observational studies Weak recommendation, best action may differ depending on circumstances or patients’ or societal values 2C Weak recommendation, Low- or very-low-quality evidence Uncertainty in the estimates of benefits, risks, and burden; benefits, risk, and burden may be closely balanced Observational studies or case series Very weak recommendations; other alternatives may be equally reasonable 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. FIGURE 1.: PRISMA literature search flow sheet.MEDICALLY REFRACTORY ULCERATIVE COLITIS 1. A multidisciplinary approach including early surgical consultation should be used to guide optimal care in hospitalized patients with moderate-to-severe UC undergoing escalation of medical therapy. Grade of recommendation: Strong recommendation based on low-quality evidence, 1C. The goal for treating UC is to resolve symptoms and achieve mucosal healing, defined as the resolution of inflammatory changes on endoscopic evaluation. Determining the extent and severity of disease is critical to selecting appropriate medical management. The extent of disease should be characterized anatomically (eg, the Montreal classification designates proctitis as E1, left-sided colitis as E2, and extensive colitis as E3).20,21 Disease severity is commonly classified according to the Truelove and Witts criteria but may also be classified according to the Seo Index, Rachmilewitz Index, Simple Clinical Colitis Activity Index, or the Mayo Score.22–28 The 2019 American College of Gastroenterology guidelines proposed using a modified and more comprehensive version of the Truelove and Witts criteria that incorporated inflammatory markers including fecal calprotectin and endoscopic disease assessment.1 When patients clinically deteriorate or have increased endoscopic disease severity, escalation of medical therapy may be needed, and utilizing a disease severity index allows for serial evaluations over time and can facilitate evolving treatment approaches. Outpatient management of UC in conjunction with gastroenterology is beyond the scope of this guideline but is reviewed in other guidelines.1,29 In the in-patient setting, it can be difficult to predict which patients should continue with escalation of medical therapy and which should undergo surgical intervention. Individualized assessment and decision making under these circumstances should take into account patient-specific preferences, previous medical therapy including exposure to monoclonal antibodies, and concomitant risk factors for requiring a total abdominal colectomy including age at diagnosis of less than 40 years, extensive colitis, severe endoscopic disease with spontaneous bleeding and deep ulcerations, previous hospitalization for colitis, elevated C-reactive protein or erythrocyte sedimentation rate, and low serum albumin.30–32 In hospitalized patients with a UC flare, intravenous methylprednisolone 40 to 60 mg daily is typically recommended as first-line therapy.1 In general, these patients should be continued on a diet, as tolerated, because bowel rest while on intravenous corticosteroids has shown no added benefit in 2 randomized, controlled trials,33,34 prophylaxis against thromboembolism should be initiated, and plain films should be obtained, as needed, to assess for toxic megacolon. Meanwhile, patients under these circumstances typically undergo endoscopy to assess disease severity and are tested for cytomegalovirus and Clostridioides difficile. Patients with UC receiving medical therapy in this setting are monitored for signs of a clinical response, including decreased stool frequency and hematochezia, a downward trend in serum C-reactive protein, and a general improvement in their overall condition.35,36 More recently, fecal calprotectin has been used to monitor disease activity and has gained acceptance as a surrogate for mucosal healing.1 If there is insufficient improvement in the 3 to 5 days after initiation of corticosteroids, intravenous infliximab at a dose of 5 to 10 mg/kg or intravenous cyclosporine is typically considered as “rescue therapy.”1 Both infliximab and cyclosporine have a mean response time of approximately 5 to 7 days in randomized, controlled trials; close observation during this initial 7-day treatment window is typically recommended with colectomy reserved for patients who do not respond appropriately or clinically worsen during this interval.27,35–38 A review of standard versus intensive infliximab dosing under these circumstances is beyond the scope of this guideline. In patients whose condition plateaus after a period of initial improvement, the need and timing for colectomy may be difficult to judge. Second-line infliximab or cyclosporine therapy in corticosteroid nonresponders avoids colectomy in 60% to 80% of patients up to 3 months after the acute episode and in greater than 60% of patients up to 5 years after the acute episode; however, those who avoid a colectomy at their index admission have a high risk of requiring a future colectomy.37,39–43 In patients treated with a third-line “rescue” therapy (eg, cyclosporine for infliximab nonresponders or infliximab for cyclosporine nonresponders) colectomy-free rates may approach 70% at 3 months and 40% to 60% at 1 year after the acute episode.44,45 However, the potential risks of using a third-line therapy can be considerable; a systematic review documented that adverse events, serious infection, and death occurred in 23%, 7%, and 1% of patients treated with this approach.46 In particular, persistent colonic distention under these circumstances characterizes a subgroup of patients who typically respond poorly to further medical therapy and are at increased risk for developing toxic megacolon. Prolonged nonoperative care of these patients can exhaust their physiological reserve and risks increased morbidity including colonic perforation.45,47 Other biologics (eg, vedolizumab, ustekinumab) and the janus kinase (JAK) inhibitor, tofacitinib, have not yet been adequately evaluated in acute, severe UC requiring hospitalization; however, small case series regarding tofacitinib and ustekinumab support their use under these circumstances.48,49 When escalating the medical care of hospitalized patients with UC, early surgical consultation should be considered to optimize patient education and position surgery as a relevant treatment option when there has been an insufficient response to the escalation of medical therapy. This approach also allows for the longitudinal surgical evaluation of a patient’s clinical course and ongoing discussion and coordination with the treating gastroenterology team. Consensus statements recommend surgical consultation for hospitalized patients with UC who do not show signs of improvement within 72 hours of initiating intravenous corticosteroids or rescue therapy, because early operative intervention has been associated with decreased postcolectomy complications.35,36,50–53 Additional considerations include early involvement of an enterostomal therapist to facilitate stoma education, establish perioperative ostomy care, appropriately mark the anticipated stoma location, and alleviate patients’ anxiety.45,54 2. Patients with severe medically refractory UC, fulminant colitis, toxic megacolon, or colonic perforation should typically undergo total abdominal colectomy with end ileostomy. Grade of recommendation: Strong recommendation based on low-quality evidence, 1C. Acutely worsening patients are at risk for developing fulminant colitis or toxic megacolon. Fulminant colitis represents a severe form of acute colitis that may involve more than 10 bloody stools per day, bleeding, a blood transfusion requirement, an erythrocyte sedimentation rate >30 mm/h, fever, tachycardia, and abdominal pain and distension.36,55 Radiographic findings under these circumstances can include colonic dilation and a thick, edematous colon wall with thumb printing.36,56 Meanwhile, toxic megacolon, an extreme form of colitis, is usually associated with a thin colon wall and total or segmental colonic dilation (diameter ≥5.5 cm) without a mechanical obstruction but with systemic toxicity.57 In practice, in the setting of severe, medically refractory UC, fulminant colitis, or toxic megacolon, clinical deterioration and typical signs of impending or contained (ie, sealed) perforation or peritonitis may be masked by ongoing immunosuppressive medical therapy.58,59 In a retrospective study of 89 patients who have IBD with fulminant colitis (n = 72; 81%) and toxic colitis (n = 17; 19%) who required colectomy, 14 (16%) had a colon perforation identified either immediately before or during surgery, most often in the cecum or distal third of the transverse colon.55 Given that mortality rates increase with longer intervals between colonic perforation and surgical intervention, especially in the setting of multisystem organ failure, fulminant colitis or toxic megacolon should prompt urgent total abdominal colectomy with end ileostomy.58,60–64 A proctectomy is usually avoided under these circumstances,65,66 and, given the concerns for developing a rectal stump dehiscence, a variety of maneuvers can be utilized, such as implanting the rectal stump in the subcutaneous tissues, creating a mucous fistula instead of a rectal stump, or decompressing the rectal stump transanally via a rectal tube.67 3. A staged approach for an IPAA should typically be considered in patients being treated with high-dose corticosteroids or monoclonal antibodies. Grade of recommendation: Strong recommendation based on low-quality evidence, 1C. Although the efficacy of corticosteroids for the treatment of acute and refractory UC has been well established, preoperative exposure to corticosteroids is associated with adverse postoperative outcomes.28,68–71 Preoperative high-dose corticosteroids, defined as >20 mg of prednisone equivalents per day, are associated with significantly increased postoperative infectious complications, although the duration of high-dose corticosteroid use that predisposes to increased risk is not well defined.72,73 Recognizing this risk, patients maintained on high-dose corticosteroids should typically undergo total abdominal colectomy and end ileostomy as their initial stage rather than a total proctocolectomy with IPAA to reduce the risk of anastomotic leak and pelvic sepsis, the leading causes of pouch failure.74–77 After a staged total abdominal colectomy, proctectomy with IPAA should typically be delayed until corticosteroids have been weaned because of the increased risk of anastomotic leak and pelvic sepsis related to these medications.77 Meanwhile, immunomodulators (eg, 6-mercaptupurine, azathioprine, and methotrexate), originally used as monotherapy for maintenance of remission before the era of biologic therapy and now used in conjunction with biologics to reduce immunogenicity primarily associated with anti-tumor necrosis factor (TNF) agents, have not been associated with increased postoperative complications according to single-center series and systematic reviews.78–83 The decision to perform a proctocolectomy and IPAA in a staged fashion should not typically be influenced by immunomodulator exposure. The relationship between monoclonal antibody therapy and adverse postoperative outcomes in the setting of UC remains controversial.82–89 Most studies show no significant association between the use of preoperative anti-TNF therapy and postoperative complications.86,87,90–97 However, the 2 largest, single-center series evaluating preoperative exposure to anti-TNF therapy at the time of IPAA showed significantly increased rates of anastomotic leak and pelvic sepsis with anti-TNF exposure.86,87 Similarly, the largest, relevant meta-analysis of patients with UC showed a significantly increased risk of both early complications after IPAA (OR, 4.12; 95% CI, 2.37–7.15) and late (postileostomy closure) complications (OR, 2.27; 95% CI, 1.27–4.05) in patients exposed to anti-TNF therapy before undergoing IPAA.98 In addition, a large, retrospective review using data from an insurance claims database found significantly increased rates of postoperative complications following IPAA in the setting of preoperative exposure to anti-TNF therapy.99 However, in contrast, the largest prospective study to date (the PUCCINI trial presented at Digestive Disease Week, San Diego, CA, in 2019) did not show any association between monoclonal antibodies or their associated drug levels and adverse postoperative outcomes.100 Likewise, a prospective study of preoperative serum anti-TNF drug levels from 94 consecutive patients with UC found no association between increased serum drug levels and adverse outcomes after surgery.101 As with anti-TNF medications, the literature remains controversial regarding whether preoperative exposure to newer classes of monoclonal antibodies or small-molecule inhibitors influences postoperative outcomes. Two single-center, retrospective series reported no significant increases in post-IPAA complications after preoperative exposure to vedolizumab, but a multicenter, retrospective review including both patients with UC and with Crohn’s disease reported significantly increased rates of infectious complications after abdominal operations in patients exposed to vedolizumab compared with patients exposed to anti-TNF medication.97,102,103 Ustekinumab, an anti-interleukin approved for UC treatment in 2019, has not yet been studied with regard to postoperative outcomes in patients with UC. Tofacitinib, approved for UC treatment in 2018, has also not yet been evaluated regarding postoperative outcomes. Recognizing the ongoing controversy, it is possible that a staged approach to proctocolectomy and IPAA in the setting of monoclonal antibody therapy may mitigate the risk of postoperative pelvic sepsis, especially in patients with additional risk factors such as anemia, poor nutrition, >10% weight loss in the 6 months before the operation, or a BMI <18 kg/m2.104 ULCERATIVE COLITIS-ASSOCIATED COLORECTAL NEOPLASIA 4. Patients with UC should undergo endoscopic surveillance at regular intervals. Chromoendoscopy or high-definition white-light endoscopy is typically recommended for optimal surveillance. Grade of recommendation: Strong recommendation based on moderate-quality evidence, 1B. Compared with age-matched controls, patients with UC are at increased risk for developing colorectal cancer (CRC).105 Risk factors for CRC in patients with UC include younger age at the time of diagnosis of UC, longer duration of disease, increased extent of disease (pancolitis carries a greater risk than proctitis or left-sided disease), severity of disease and inflammation (quiescent disease carries a lower risk), a family history of CRC especially if diagnosed before the age of 50, and the presence of primary sclerosing cholangitis (PSC).106 However, recent reports suggest that the risk for developing CRC in the setting of UC has been decreasing over time.107 Previous reports suggested a 2%, 8%, and 18% cumulative risk of CRC 10, 20, and 30 years after the diagnosis of UC, whereas more recent meta-analyses report a cumulative risk of 1%, 3%, and 7%.108–110 Given the risk of neoplasia, surveillance colonoscopy for patients with UC is endorsed by multiple societies; however, controversy persists regarding the optimal timing for initiating screening and recommended surveillance intervals.111 Regardless of the extent of disease at initial diagnosis, patients should undergo a screening colonoscopy within 8 years of the onset of symptoms. The recommended intervals for subsequent surveillance endoscopic examinations are determined by individualized risk assessment and vary by different societies’ guidelines.112–114 Recognizing their significantly increased risk for neoplasia, patients with PSC should begin screening at the time of diagnosis and undergo surveillance annually. The European Crohn’s and Colitis Organization recommends that the highest-risk patients, those with PSC or a history of dysplasia or stricture, undergo annual colonoscopy, that intermediate-risk patients with extensive or long-standing colitis or a family history of CRC undergo colonoscopy every 2 to 3 years, and that low-risk patients utilize a 5-year interval. Surveillance colonoscopy should, ideally, be performed when the colonic disease is in remission.115 Meanwhile, the American Society for Gastrointestinal Endoscopy recommends that patients with PSC, active inflammation, a history of dysplasia or CRC in a first-degree relative, or an anatomic abnormality such as a stricture have annual surveillance colonoscopy and that average-risk patients undergo surveillance colonoscopy every 1 to 3 years.116,117 Of note, patients with UC 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 Surveillance colonoscopy for patients with UC, according to American Society for Gastrointestinal Endoscopy and American Gastroenterological Association guidelines, is typically recommended using high-definition white-light colonoscopy with nontargeted (ie, random) 4-quadrant biopsies (typically taken at 10-cm intervals with a total of ≥32 biopsies) or using chromoendoscopy with targeted biopsies.112,113,117,121 Early studies suggested that chromoendoscopy was superior to standard white-light endoscopy for detecting adenomas with or without surrounding dysplasia and resulted in improved dysplasia detection with fewer overall biopsies.116,122–127 However, endoscopy with high-definition white-light platforms has demonstrated similar dysplasia detection during surveillance colonoscopy compared with chromoendoscopy under these circumstances.1,128,129 In addition, the infrastrucure required for widespread adoption of chromoendoscopy surveillance may be a barrier to implementation given the increased endoscopy time and associated expenses typically related to chromoendoscopy and the relatively limited technical expertise available among endoscopists in practice.130 For these reasons, high-definition white-light colonoscopy or chromoendoscopy can be used for surveillance examinations depending on availability and local expertise. Meanwhile, because most dysplasia under these circumstances is visible with high-definition colonoscopy, performing surveillance with random biopsies has been called into question; the decision to perform targeted biopsies only or to also obtain random biopsies may be individualized based on risk factors (eg, PSC, previous dysplasia found on random biopsy).1 A prospective multicenter study of 1000 patients with IBD undergoing surveillance colonoscopy in France from 2009 to 2011 reported 94 patients with dysplasia. The yield of dysplasia found by random biopsies was 0.2% (68 of 31,865 biopsies), but only 12 of the 94 patients (13%) with dysplasia were diagnosed by random biopsies. Of note, dysplasia found by random biopsies was associated with a personal history of dysplasia, a colon with loss of compliance and folds, and PSC; therefore, this study recommended random biopsies during surveillance colonoscopies for patients with these risk factors.131 Finally, a recent randomized, controlled trial of 305 patients with IBD from a single center in Sweden undergoing surveillance colonoscopy with both random and targeted biopsies found that high-definition chromoendoscopy was superior to high-definition white-light endoscopy in terms of detecting neoplasia.132 In this study, colonoscopies with dye-spray chromoendoscopy took an average of 7 minutes longer than the white-light examinations. 5. Patients with visible polypoid or nonpolypoid dysplasia that is completely excised endoscopically should undergo endoscopic surveillance. Patients with visible dysplasia not amenable to endoscopic excision, invisible dysplasia in the flat mucosa surrounding a visible dysplastic lesion, or colorectal adenocarcinoma should typically undergo total proctocolectomy with or without IPAA. Grade of recommendation: Strong recommendation based on moderate-quality evidence, 1B. In patients with colitis, endoscopic biopsies may be classified as negative for dysplasia, indefinite for dysplasia, low-grade dysplasia (LGD), or high-grade dysplasia (HGD) based on histopathology assessment. In general, pathology determinations under these circumstances should be confirmed by a second appropriately trained pathologist because of high interobserver variability.112,133 Indefinite dysplasia is addressed in statement 6. Regarding the grades of dysplasia, LGD and HGD are differentiated based on the distribution of nuclei within the cells of the mucosa; LGD is characterized by nuclei confined to the basal half of the cells, whereas HGD has nuclei located haphazardly throughout the mucosa.74,78 The terms dysplasia-associated lesion or mass and adenoma-like mass have been replaced with more simplified descriptors of visible or invisible lesions.134 Visible lesions are described morphologically by the Paris classification as polypoid (eg, pedunculated or sessile) or nonpolypoid (eg, slightly elevated, flat, or depressed) and borders of lesions are classified as distinct or indistinct.117 Retrospective studies indicate that 64% to 92% of colorectal dysplasia in patients with UC is visible.135–137 Other noteworthy descriptors include ulceration and features of potential submucosal