The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Treatment of Left-Sided Colonic Diverticulitis

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 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, https://links.lww.com/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 references 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.TABLE 1.: The GRADE System: grading recommendationsFIGURE 1.: PRISMA literature search flow sheet.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 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 >150 mg/L significantly discriminated acute uncomplicated from complicated diverticulitis and the combination of CRP >150 mg/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. 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. 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 antibiotic-free approach can be successful in the outpatient setting.42 A number of other systematic reviews and meta-analyses have also supported this approach.37,43–46 A meta-analysis 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 >170 mg/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 meta-analysis 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 initial episode of diverticulitis was treated with oral versus intravenous antibiotics.37 3. Image-guided percutaneous drainage is usually recommended for stable patients with abscesses >3 cm in size. Grade of Recommendation: Strong recommendation based on moderate-quality evidence, 1B. Complicated diverticulitis with abscess formation occurs in 15% to 40% of patients who present with acute sigmoid diverticulitis. Overall, nonoperative treatment with either antibiotics alone or in combination with percutaneous drainage is successful in up to 80% of cases.50–52 Treatment failure is typically defined as requiring surgery, developing worsening sepsis, or having a recurrent abscess within 30 days.53 Antibiotic treatment alone for abscesses smaller than 3 cm is typically successful and, in stable patients, treatment can usually be administered in the outpatient setting. When this approach fails, percutaneous drainage should be considered, particularly in patients with larger abscesses (>3 cm) where antibiotics alone have a much higher failure rate (up to 34%).53,54 There is no correlation between abscess size and failure of percutaneous drainage.53,55,56 Although recurrence after antibiotic treatment of diverticular abscesses ranges from 25% to 60% of patients, recurrence after percutaneous drainage is significantly lower (15%–25%).50,57,58 Patients who do not have a safe access window for percutaneous drainage or who do not respond to medical treatment including percutaneous drainage should typically be considered for surgery. Laparoscopic abscess drainage rather than surgical resection can be considered in certain cases.59 4. Tobacco cessation, reduced meat intake, physical activity and weight loss are recommended interventions to potentially reduce the risk of diverticulitis. Grade of Recommendation: Strong recommendation based on low-quality evidence, 1C. The progression of normal colonic architecture to diverticulosis and subsequent diverticulitis is not well understood but is multifactorial and involves diet, genetics, lifestyle, and, possibly, the microbiome.60,61 In a prospective cohort study of 46,295 men from the Health Professionals Follow-Up Study, a "Western" dietary pattern (high in red meat, refined grains, and high-fat dairy) was associated with an increased risk of diverticulitis when compared to a "prudent approach" (high in fruits, vegetables, and whole grains). Men who consumed the highest quintile of a Western dietary pattern had a multivariate hazard ratio of 1.55 (95% CI, 1.20–1.99) for diverticulitis compared with men in the lowest quintile, and the authors attributed the association primarily to the intake of less fiber and more red meat.62 Liu et al63 demonstrated a similar pattern when they studied 907 incident cases of diverticulitis that were prospectively identified during 757,791 person-years of follow-up. They defined patients with a low-risk lifestyle as those who had an average red meat intake (<51 g per day), dietary fiber intake in the top 40% of the cohort (about 23 g per day), approximately 2 hours of exercise weekly, normal BMI between, and never smoked. They found an inverse linear relationship between the number of low-risk lifestyle factors and diverticulitis incidence (p for trend < 0.001). When all 5 low-risk factors were present, the relative risk of diverticular disease was 0.27 (95% CI, 0.15–0.48) leading these authors to recommend a low-risk lifestyle. A variety of agents have been studied to try to prevent recurrent attacks of diverticulitis. Although a high-fiber diet is associated with a lower risk of having a first episode of acute diverticulitis, the utility of fiber supplements in secondary prevention of diverticulitis is unclear.64–66 Aune et al67 performed a meta-analysis of 5 prospective studies that comprised 6076 cases of diverticular disease. The relative risk for having an initial episode of diverticular disease was 1.36 (95% CI, 1.15–1.61) for current smokers, 1.17 (95% CI, 1.05–1.31) for former smokers, and 1.29 (95% CI, 1.16–1.44) for the group including both current and former smokers ("ever smokers"). The relative risk for having a complication of diverticular disease (abscess or perforation) was 2.54 (95% CI, 1.49–4.33) for current smokers and 1.83 (95% CI, 1.25–2.67) for ever smokers, and the authors concluded that tobacco smoking is associated with an increased incidence of diverticular disease and its associated complications. The same authors also examined the role of obesity in a meta-analysis of 5 studies and found that the relative risk for a 5-unit increase in BMI was 1.31 (95% CI, 1.09–1.56) for having a first episode of diverticulitis and 1.20 (95% CI, 1.04–1.40) for having a diverticular disease-related complication.68 Although data are still emerging, interventions such as weight reduction and smoking cessation may be recommended as strategies to reduce the incidence of diverticulitis, but the role of these strategies in secondary prevention is unclear.67,68 5. Mesalamine, rifaximin, and probiotics are not typically recommended to reduce the risk of diverticulitis recurrence but may be effective in reducing chronic symptoms. Grade of Recommendation: Weak recommendation based on moderate-quality evidence, 2B. Interventions that have been studied with regard to the incidence of diverticulitis include mesalamine, rifaximin, and probiotics. Although some studies evaluating the efficacy of mesalamine in preventing SUDD demonstrated superiority over placebo, the majority of randomized controlled trials and meta-analyses do not demonstrate efficacy in preventing recurrence.69–73 A recent meta-analysis of 6 randomized controlled trials demonstrated no difference between mesalamine and placebo regarding recurrent diverticulitis (OR, 1.20; 95% CI, 0.96–1.50; p = 0.11). Although mesalamine does not seem to effectively reduce the incidence of recurrent diverticulitis, it may play a role in symptom resolution in patients with SUDD.69,70 A number of studies examining the efficacy of rifaximin in secondary prevention of acute diverticulitis reported promising results, albeit these utilized questionable methodology. In one study, patients were randomly assigned to a high-fiber diet with or without rifaximin, but, because of poor accrual, the study design was changed to a feasibility study and the study accrued only 165 patients. The study demonstrated a lower rate of recurrent diverticulitis in the fiber + rifaximin group in comparison with the fiber-alone group (10.4% versus 19.3%).74 Another retrospective cohort of 142 patients with symptomatic diverticular disease treated with rifaximin demonstrated a reduction in disease symptoms like abdominal pain and tenderness, bloating, and disturbances in bowel habits.75 An older meta-analysis of 4 randomized controlled trials including 1660 patients found that rifaximin plus fiber supplementation is effective in obtaining symptom relief at 1 year.76 Other studies have explored the possible effect of probiotics on the incidence of diverticulitis, although no standard probiotic regimen was used. A randomized controlled trial evaluated the effect of a combination of mesalamine and probiotics on recurrence of SUDD defined as the recurrence of abdominal pain scored as ≥5 (0 = best; 10 = worst) for at least 24 consecutive hours. A total of 210 patients were randomly assigned to mesalamine 1.6 g/day plus Lactobacillus casei placebo, active L casei plus mesalamine placebo, active L casei plus active mesalamine, and L casei placebo plus mesalamine placebo for 10 days per month for 12 months.77 The authors found that Lactobacillus and mesalamine in combination reduced the chances of recurrence. These results must be interpreted with caution because the primary outcome was recurrence of symptoms and there was no evidence presented regarding patients' burden of disease as measured by imaging or inflammatory markers. In general, studies evaluating the use of mesalamine, rifaximin, or probiotics are heterogeneous, and the routine use of these agents following an attack of diverticulitis is typically not recommended.66 EVALUATION AFTER RECOVERY FROM ACUTE DIVERTICULITIS 1. After resolution of an episode of acute complicated diverticulitis, the colon should typically be endoscopically evaluated to confirm the diagnosis if a colonoscopy has not been performed recently. Grade of Recommendation: Strong recommendation based on low-quality evidence, 1C. Patients with complicated diverticulitis are at risk of actually harboring an occult malignancy.78,79 A systematic review and meta-analysis by Sharma and colleagues80 demonstrated that the risk of malignancy was 11% in patients with complicated diverticulitis and was 0.7% in those with uncomplicated diverticulitis. Another recent systematic review found that the incidence of malignancy was 7.9% (95% CI, 3.9%–15.3%) in patients with complicated diverticulitis and was 1.3% (95% CI, 0.1%–2%) in those with uncomplicated diverticulitis.81 The colon should typically be evaluated to exclude a malignancy in patients who have had an episode of complicated diverticulitis, and this examination is often performed about 6 weeks after the acute episode to decrease the likelihood of a procedure-related perforation.1 It should be noted, however, that the data supporting this timing are scant. Lahat et al82 randomly assigned 86 patients diagnosed with acute diverticulitis to either early colonoscopy during the index hospitalizaton (n = 45) or late colonoscopy 6 weeks later (n = 41). The study showed no differences in terms of safety or complications related to colonoscopy, and the authors concluded that early colonoscopy is feasible and safe under these circumstances. These data should be interpreted with caution because the authors did not report a sample size calculation or power analysis, and the results could be subject to a type II error. Specific CT findings associated with an increased likelihood of finding occult malignancy on endoscopy include abscess, "shouldering" where the leading edges of the presumed inflammatory mass have a shelf-like appearance, obstruction, and mesenteric or retroperitoneal lymphadenopathy.79,83 Multiple series and one systematic review have found that patients with uncomplicated diverticulitis diagnosed on CT are at risk of having colorectal cancer or advanced polyps similar to the general population and may not require further colonoscopies beyond those recommended for screening.84–87 However, if imaging, symptoms (eg, narrowed stools, bleeding), or clinical recovery is atypical, patients with uncomplicated diverticulitis should typically undergo further assessment with colonoscopy.88 ELECTIVE SURGERY FOR ACUTE DIVERTICULITIS 1. After successful nonoperative treatment of a diverticular abscess, elective resection should typically be considered