The American Society of Colon and Rectal Surgeons Clinical ...
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CLINICAL PRACTICE GUIDELINES
The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Treatment of Left-Sided Colonic Diverticulitis
Jason Hall, M.D., M.P.H.1 ? Karin Hardiman, M.D., Ph.D.2 ? Sang Lee, M.D.3 Amy Lightner, M.D.4 ? Luca Stocchi, M.D.5 ? Ian M. Paquette, M.D.6 Scott R. Steele, M.D., M.B.A.4 ? Daniel L. Feingold, M.D.7 ? Prepared on behalf of the Clinical Practice Guidelines Committee of the American Society of Colon and Rectal Surgeons
1 Section of Colon and Rectal Surgery, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts 2 Division of Gastrointestinal Surgery, University of Alabama at Birmingham, Birmingham, Alabama 3 Division of Colon and Rectal Surgery, USC Keck School of Medicine, Los Angeles, California 4 Department of Colorectal Surgery, Cleveland Clinic Cleveland, Cleveland, Ohio 5 Division of Colorectal Surgery, Mayo Clinic Florida, Jacksonville, Florida 6 Division of Colon and Rectal Surgery, University of Cincinnati, Cincinnati, Ohio 7 Section of Colorectal Surgery, Rutgers University, New Brunswick, New Jersey
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
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Funding/Support: None reported.
Financial Disclosures: None reported.
Correspondence: Daniel L. Feingold, M.D., Professor and Chair, Section of Colorectal Surgery, Rutgers University, New Brunswick, NJ.
Dis Colon Rectum 2020; 63: 728?747 DOI: 10.1097/DCR.0000000000001679 ? The ASCRS 2020
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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 or 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 in light of all the circumstances presented by the individual patient.
METHODOLOGY
These guidelines are constructed on the platform of the previously published Practice Parameters for the Treatment of Sigmoid Diverticulitis published by the American Society of Colon and Rectal Surgeons (ASCRS) in 2014.1 A systematic search was conducted under the guidance of an information services librarian. This search strategy is outlined under the search appendices (see Supplemental Digital Content, http:// links.DCR/B209). The PubMed, EMBASE, Cochrane, and Web of Science databases were searched from January 1, 2013, until October 26, 2019. Relevant manuscripts identified by individual authors were also included. Key word combinations using the MeSH terms including "Diverticulitis," "Diverticulosis," "Diverticular," "Colonic," "Colon Diverticulosis," "Surgery," "Medical Therapy," "Antibiotics," "Probiotics," "Laparoscopic Lavage," "Mesalamine," "Rifaximin," and "Surgery" were performed. The search was limited to English language abstracts with human subjects. A directed search of ref-
DISEASES OF THE COLON & RECTUM VOLUME 63: 6 (2020)
DISEASES OF THE COLON & RECTUM VOLUME 63: 6 (2020)
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erences embedded in the candidate publications was also performed. Emphasis was placed on prospective trials, meta-analyses, systematic reviews, and practice guidelines. Peer-reviewed observational studies and retrospective studies were included when higher-quality evidence was insufficient. In brief, a total of 4885 unique journal titles were identified. Initial review of the search results led to the exclusion of 4223 titles based on irrelevance of the title or because they consisted of a case report, letter to the editor, or nonsystematic review. A review of the remaining 662 titles included assessment of the full-length articles. This led to exclusion of an additional 494 titles for which similar but higher-level evidence was available. The remaining 168 titles were considered for grading of the recommendations (Fig. 1). The final source material used was evaluated for the methodological quality, the evidence base was examined, and a treatment guideline was formulated by the subcommittee for this guideline. The final grade of recommendation and level of evidence for each statement were determined using the Grades of Recommendation, Assessment, Development, and Evaluation system (Table 1).2 When agreement was incomplete 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 publication. Recommendations formulated by the subcommittee were reviewed by the entire Clinical Practice Guidelines Committee. The submission was peer-reviewed by Diseases of the Colon & Rectum and the final recommendations were approved by the ASCRS Executive Council. 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 to this material.
The terms uncomplicated and complicated diverticulitis, symptomatic uncomplicated diverticular disease (SUDD), and recurrent diverticulitis are used throughout this document. For purposes of this guideline, complicated diverticulitis is defined as diverticulitis associated with uncontained, free perforation with a systemic inflammatory response, fistula, abscess, stricture, or obstruction. Micro-perforation with small amounts of contained, extraluminal gas, in the absence of a systemic inflammatory response, is not considered complicated diverticulitis. Uncomplicated diverticulitis is defined as diverticulitis that is not associated with any of the aforementioned features.3 Symptomatic uncomplicated diverticular disease is defined as diverticulosis with associated chronic abdominal pain in the absence of clinically overt colitis.4 Meanwhile, the term recurrent diverticulitis has no universally accepted definition and
the studies reviewed in this guideline used and defined recurrence differently.
STATEMENT OF THE PROBLEM
The prevalence of diverticular disease has risen steadily in industrialized nations over the past few decades.5,6 A 2016 study using data from the National Inpatient Sample estimated that the prevalence of hospitalization for diverticulitis increased from 74.1 of 100,000 in 2000 to a peak of 96.0 of 100,000 in 2008.7 These authors found that there were 2,151,023 hospitalizations for diverticulitis during this time period with an average of 195,548 admissions per year.7 Another study compiled data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey and found that in 2010 there were more than 2.7 million discharges in the ambulatory setting associated with a diagnosis of diverticular disease, and that in 2012 there were more than 340,000 emergency department visits associated with a diagnosis of diverticulitis and 215,560 of these patients were admitted. Admission was associated with a median length of stay of 4 days and a median cost of treatment of US $6333.8 The authors recently used updated data from the same 2 surveys and estimated that in 2014 there were 1.92 million patients diagnosed with diverticular disease in the ambulatory setting.9
Another contemporary analysis demonstrated that the rate of diverticulitis-related emergency department visits rose 26.8% from 89.8 to 113.9 visits per 100,000 population between 2006 and 2013 and that the aggregate national cost of these visits was $1.6 billion in 2013.10
As our understanding of diverticulitis has evolved, so have recommendations for the clinical management of these patients. Patients with diverticular disease are increasingly being treated as outpatients. Rates of admission to the hospital after emergency department evaluation for diverticulitis dropped from 58.0% in 2006 to 47.1% in 2013.10 In addition, fewer patients are undergoing emergency bowel surgery; the rate of patients undergoing an intestinal operation per emergency department visit for diverticulitis decreased from 7278 of 100,000 to 4827 of 100,000 between 2006 and 2013.10 Concomitantly, there has been an increase in the use of elective and laparoscopic surgery in the management of diverticulitis.11
This publication summarizes the changing treatment paradigm for patients with left-sided diverticulitis. Although diverticular disease can affect any segment of the large intestine, we will focus on left-sided disease. Bowel preparation, enhanced recovery pathways, and prevention of thromboembolic disease, while relevant to the management of patients with diverticulitis, are beyond the scope of these guidelines and are addressed in other ASCRS clinical practice guidelines.12?14
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HALL ET AL: TREATMENT OF LEFT-SIDED COLONIC DIVERTICULITIS
Identification
Records identified through database searching (n = 7563)
Additional records identified through other sources (n = 87 )
Screening
Records after duplicates removed (n = 4885 )
Records screened (n = 4885)
Articles & abstracts assessed for eligibility (n = 662)
Studies referenced in final manuscript (n = 168)
Records excluded (n = 4223) ? Commentary/letters ? Irrelevant/unrelated ? Case reports ? Review ? No abstract
Full-text articles excluded due to available higher level evidence
(n= 494)
Eligibility
Included
FIGURE 1. PRISMA literature search flow sheet.
INITIAL EVALUATION OF ACUTE DIVERTICULITIS
1. The initial evaluation of a patient with suspected acute diverticulitis should include a problem-specific history and physical examination and appropriate laboratory evaluation. Grade of Recommendation: Strong recommendation based on low-quality evidence, 1C.
Classic findings related to sigmoid diverticulitis include left lower quadrant pain, fever, and leukocytosis. Fecaluria, pneumaturia, or pyuria are concerning for possible colovesical fistula, and stool per vagina is concerning for possible colovaginal fistula.
Physical examination, complete blood count, urinalysis, and abdominal radiographs can be helpful in refining the differential diagnosis. Other diagnoses to consider when patients present with suspected diverticulitis may include constipation, irritable bowel syndrome, appendicitis, IBD, neoplasia, kidney stones, urinary tract infection, bowel obstruction, and gynecologic disorders.
C-reactive protein (CRP), procalcitonin, and fecal calprotectin have been explored as potential predictors of diverticulitis severity.15?17 C-reactive protein has been assessed as a marker of complicated diverticulitis
in multiple case series in an attempt to identify a biomarker that can discriminate patients who have complicated disease. Many of the series are small and the suggested cutoff values vary.18?22 However, in one retrospective study of 350 patients presenting with their first episode of diverticulitis, CRP >150mg/L significantly discriminated acute uncomplicated from complicated diverticulitis and the combination of CRP >150mg/L and free fluid on CT scan was associated with a significantly greater risk of mortality.23 In a study of 115 patients, Jeger et al15 demonstrated that procalcitonin was able to discriminate between patients with uncomplicated and complicated disease. Another study of 48 patients demonstrated that elevated fecal calprotectin was associated with diverticulitis recurrence.17 Recently, a diagnostic prediction model differentiating uncomplicated diverticulitis from complicated diverticulitis (defined as Hinchey >Ia) was developed. Incorporating 3 parameters, abdominal guarding, CRP, and leukocytosis, this validated model had a negative predictive value for detecting complicated diverticulitis of 96%.24 Additional studies are needed to elucidate the utility of laboratory testing in the setting of diverticulitis and, currently, the limited evidence does not support a particular management algorithm.
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TABLE 1. The GRADE System: grading recommendations
Grade Description
Benefit versus risk and burdens
Methodological quality of supporting evidence
Implications
1A
Strong recommendation, Benefits clearly outweigh RCTs without important limitations
Strong recommendation, can
High-quality evidence
risk and burdens or vice
or overwhelming evidence from
apply to most patients in
versa
observational studies
most circumstances without
reservation
1B
Strong recommendation, Benefits clearly outweigh RCTs with important limitations
Strong recommendation, can
Moderate-quality
risk and burdens or vice
(inconsistent results,
apply to most patients in
evidence
versa
methodological flaws, indirect, or
most circumstances without
imprecise) or exceptionally strong
reservation
evidence from observational studies
1C
Strong recommendation, Benefits clearly outweigh Observational studies or case series
Strong recommendation but may
Low- or very-low-quality
risk and burdens or vice
change when higher-quality
evidence
versa
evidence becomes available
2A
Weak recommendation,
Benefits closely balanced RCTs without important limitations
Weak recommendation, best
High-quality evidence
with 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 RCTs with important limitations
Weak recommendation, best
Moderate-quality
with risks and burdens
(inconsistent results,
action may differ depending
evidence
methodological flaws, indirect or
on circumstances or patients' or
imprecise) or exceptionally strong
societal values
evidence from observational studies
2C
Weak recommendation,
Uncertainty in the
Observational studies or case series
Very weak recommendations;
Low- or very-low-quality
estimates of benefits,
other alternatives may be
evidence
risks and burden;
equally reasonable
benefits, risk and
burden 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?181.2 Used with permission.
2. CT scan of the abdomen and pelvis is the most appropriate initial imaging modality in the assessment of suspected diverticulitis. Grade of Recommendation: Strong recommendation based on moderate-quality evidence, 1B.
Computed tomography imaging has become a standard tool to diagnose diverticulitis, assess disease severity, and help devise a treatment plan. Low-dose CT, even without oral or intravenous contrast media, is highly sensitive and specific (95% for each) for diagnosing acute abdominal complaints including diverticulitis as well as other etiologies that can mimic the disease.25 Computed tomography findings associated with diverticulitis may include colonic wall thickening, fat stranding, abscess, fistula, and extraluminal gas and fluid and can stratify patients according to Hinchey classification.26 The utility of CT imaging goes beyond the accurate diagnosis of diverticulitis; the grade of severity on CT correlates with the risk of failure of nonoperative management in the short term and with long-term complications such as recurrence, the persistence of symptoms, and the development of colonic stricture and fistula.27?29
3. Ultrasound and MRI can be useful alternatives in the initial evaluation of a patient with suspected acute diverticulitis when CT imaging is not available or is
contraindicated. Grade of Recommendation: Strong recommendation based on low-quality evidence, 1C.
Ultrasound and MRI may be useful in patients with a contrast allergy where CT can be challenging or in pregnant patients. Ultrasound can be particularly useful to rule out other causes of pelvic pain that can mimic diverticulitis when the diagnosis is unclear, especially in women.30 However, ultrasound can miss complicated diverticulitis and thus should not typically be the only imaging modality utilized if this is suspected.31 Although ultrasound evaluation is included as a diagnostic option in the practice guidelines of several societies, ultrasound is user dependent and its utility in obese patients may be limited.32,33 Where available, MRI can also be useful in patients in whom CT is contraindicated and may be better than CT at differentiating neoplasia from diverticulitis.34
MEDICAL MANAGEMENT OF ACUTE DIVERTICULITIS
1.Selected patients with uncomplicated diverticulitis can be treated without antibiotics. Grade of Recommendation: Strong recommendation based on high-quality evidence, 1A.
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HALL ET AL: TREATMENT OF LEFT-SIDED COLONIC DIVERTICULITIS
Until recently, the routine use of antibiotics has been the primary treatment for patients presenting with acute diverticulitis. The generally accepted pathophysiologic mechanism of diverticulitis has been challenged because new evidence suggests that diverticulitis is primarily an inflammatory process that can result in micro-perforation rather than a complication of micro-perforation itself.4 Two randomized controlled trials as well as systematic reviews have found no significant difference in outcomes of patients with uncomplicated diverticulitis treated with or without antibiotics.35?38 The AVOD trial (Swedish acronym standing for "antibiotics in uncomplicated diverticulitis") randomly assigned 623 inpatients with CT-confirmed uncomplicated left-sided diverticulitis to receive intravenous fluids alone or intravenous fluids and antibiotics and found no differences between the treatment groups in terms of complications, recurrence, or time to recovery.35 This study group recently published a long-term follow-up of this cohort. At a median follow-up of 11 years, the authors found no significant differences between the 2 groups in terms of recurrences (both 31.3%), complications, surgery for diverticulitis, or reported quality of life (EQ-5DTM).39
The most recent randomized controlled trial (DIABOLO) from The Dutch Diverticular Disease Collaborative Study Group compared the efficacy of treating patients presenting with their first episode of sigmoid diverticulitis with antibiotics versus observation.36 Five hundred twenty-eight patients with CT-proven, uncomplicated diverticulitis were randomly assigned to either a 10-day course of amoxicillin-clavulanic acid (48 hours of intravenous treatment followed by oral administration) or observation in an outpatient setting, and the primary end point was time to recovery. The median time to recovery for the antibiotic treatment group was 12 days (interquartile range (IQR) 7?30) versus 14 days in the observation group (IQR 6?35; p = 0.15). There were no significant differences between the treatment groups in terms of the occurrence of mild or serious adverse events, but the antibiotic group had a higher rate of antibiotic-related adverse events (0.4% versus 8.3%; p = 0.006). After 24 months of follow-up, there were no significant differences between the 2 groups with regard to mortality, recurrent diverticulitis (uncomplicated or complicated), readmission, adverse events, or need for resection.40
A Cochrane review also found no significant differences in outcomes between patients with uncomplicated diverticulitis treated with or without antibiotics.41 These studies suggest that a proportion of patients with uncomplicated diverticulitis can be treated without antibiotics. It is important to emphasize that nearly all of the patients included in these studies were relatively healthy and had early-stage diverticular disease (Hinchey I and Ia). Some investigators have also demonstrated that an antibioticfree approach can be successful in the outpatient setting.42
A number of other systematic reviews and metaanalyses have also supported this approach.37,43?46 A metaanalysis of 9 studies that included 2565 patients compared the efficacy of treatment with and without antibiotics. Two studies were randomized trials, 2 were prospective cohort studies, and 5 were retrospective analyses. The authors noted that there were no differences between the 2 groups in terms of rates of treatment failure, recurrence of diverticulitis, complications, readmission rates, need for surgery, or mortality. Treatment without antibiotics was more likely to fail in patients with associated comorbidities.45 A retrospective study of 565 patients with Hinchey Ia disease found that those with a CRP >170mg/dL had a higher risk of treatment failure when treated without antibiotics.47 Another meta-analysis of 7 studies compared observational management and antibiotic treatment in 2321 patients and concluded that there were no significant differences between the groups in terms of emergency surgery (0.7% versus 1.4%; p = 0.10) and recurrence (11% versus 12%; p = 0.30). However, when the authors examined only randomized trials, elective surgery during follow-up occurred more frequently in the observational group than in the antibiotic group (2.5% versus 0.9%; p = 0.04).37 Taken as a whole, these data suggest that antibiotic therapy may not be necessary in selected, otherwise healthy patients with early-stage diverticulitis.
2.Nonoperative treatment of diverticulitis may include antibiotics. Grade of Recommendation: Strong recommendation based on low-quality evidence, 1C.
Before the 2 randomized trials questioning the benefit of antibiotics in uncomplicated diverticulitis, antibiotic therapy was and still is a standard component of the armamentarium used to treat all stages of this disease.1 The use of antibiotics continues to be appropriate for higher-risk patients with significant comorbidities, signs of systemic infection, or immunosuppression. Both of the randomized trials supporting avoidance of antibiotics included only patients with early-stage disease (Hinchey I and Ia).35,36 Therefore, the use of antibiotics continues to be appropriate in all other stages of the disease.
A randomized controlled trial of 106 patients with uncomplicated diverticulitis compared a short course of intravenous antibiotic treatment (4 days) to a more standard course (7 days) and found the shorter course was as effective as the longer course.48 Another randomized trial of 132 patients examined outpatient versus inpatient administration of antibiotics for diverticulitis and demonstrated no significant clinical outcome differences between the groups, although there was a significantly lower cost associated with outpatient treatment.49 A recent metaanalysis of 4 studies (355 patients) also suggested there was no difference in treatment failure (6% versus 7%; p = 0.60) or recurrence (8% versus 9%; p = 0.80) when the
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