Risk of Colorectal Cancer in Patients With Acute Diverticulitis: A Systematic Review and Meta-analysis of Observational Studies

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Risk of Colorectal Cancer in Patients With Acute Diverticulitis: A Systematic Review and Meta-Analysis of Observational Studies Q10

Jeremy Meyer,*,‡ Lorenzo A. Orci,*,‡ Christophe Combescure,§ Alexandre Balaphas,*,‡ Philippe Morel,*,‡ Nicolas C. Buchs,*,‡ and Frédéric Ris*,‡ *Division of Digestive and Transplantation Surgery, University Hospitals of Geneva, Genève, Switzerland; ‡Unit of Surgical Research, University of Geneva, Genève, Switzerland; and §Division of Clinical Epidemiology, University Hospitals of Geneva, Genève, Switzerland BACKGROUND & AIMS:

We performed a systematic review and meta-analysis to assess the prevalence of colorectal cancer in patients with acute diverticulitis.

METHODS:

We searched MEDLINE from inception through November 2nd, 2017 for studies reporting the prevalence of colorectal cancer in patients with diverticulitis, identified based on the protocol CRD42017083272. This systematic review was conducted in accordance to the MOOSE guidelines. Pooled prevalence values were obtained by random effects models and robustness was tested by leave-one out sensitivity analyses. Heterogeneity was assessed using the Q-test and quantified based on I2 value. The critical appraisal of included studies was performed using the Newcastle-Ottawa scale.

RESULTS:

Our final analysis included 31 studies, comprising 50,445 patients. The pooled prevalence of colorectal cancer was 1.9% (95% CI, 1.5%–2.3%). Patients with complicated diverticulitis had a significantly higher risk for colorectal cancer (prevalence, 7.9%; 95% CI, 3.9%–15.3%) than patients with uncomplicated diverticulitis (prevalence, 1.3%; 95% CI, 0.1%–2%), corresponding to a pooled prevalence ratio of 6.7 (95% CI, 2.5–18.3). Subgroup analyses did not find significant difference in prevalence when separately pooling studies according to ranking on the Newcastle-Ottawa scale, geographical location or length of follow-up. Meta-regression did not find any association between age and colorectal cancer. Among patients who underwent endoscopy, the pooled prevalence of polyps was 22.7% (95% CI, 19.6%–26.0%), of advanced adenomas was 4.4% (95% CI, 3.4%–5.8%), of adenomas was 14.2% (95% CI, 11.7%–17.1%), and of hyperplastic polyps was 9.2% (95% CI, 7.6%–11.2%).

CONCLUSION:

In a meta-analysis of observational studies of patients with acute diverticulitis, we found the pooled prevalence of colorectal cancer to be 1.9%. The risk of colorectal cancer was significantly higher in patients with complicated diverticulitis than in patients with uncomplicated diverticulitis.

Keywords: Colonoscopy; Risk Factor; Progression; Tumor; Adenocarcinoma.

olonic diverticulitis constitutes a common primary care problem, accounting for more than 200,000 admissions per year in the United States.1 Diverticulitis is usually diagnosed by computed tomography, which shows thickening and infiltration of colonic diverticula associated or not with local or distant septic complication.2 From the radiologic point of view, these findings can often be misinterpreted between colorectal cancer and diverticulitis.3 Therefore, experts recommend performing routine colonoscopy for all patients with diverticulitis.4,5 This strategy has been questioned by many groups, especially regarding patients with

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uncomplicated diverticulitis.6–10 The debate has recently led to the publication of several studies reporting rates of colonic neoplasia in patients undergoing endoscopic assessment after an episode of diverticulitis. Robust data estimating the prevalence of colorectal cancer in patients initially considered to have

Abbreviation used in this paper: CI, confidence interval. © 2018 by the AGA Institute 1542-3565/$36.00 https://doi.org/10.1016/j.cgh.2018.07.031

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diverticulitis are needed to establish whether these patients would benefit from a diagnostic endoscopy. Colonoscopy is a costly procedure, can lead to potentially lethal complications,11 and should therefore be reserved for patients presenting high risk of colorectal cancer. Our aim was to perform a systematic review and meta-analysis reporting on the prevalence of colorectal cancer in patients who have experienced an episode of acute diverticulitis.

Materials and Methods The present methodology is in accordance with the Meta-analysis of Observational Studies in Epidemiology (MOOSE) checklist12 (Supplementary Table 1). The study protocol was registered in the PROSPERO database (CRD42017083272).

Literature Search and Study Selection A literature search was conducted in MEDLINE from inception until November 2, 2017. Keyword combination was as follows: (Diverticulitis[Title/Abstract]) AND (Cancer[Title/Abstract]). Additional records were identified by manual search of the reference lists of the included publications. To be included, studies had to be written in English and to report the prevalence of colorectal cancer (adenocarcinoma) in patients with diverticulitis. We excluded case series, conference abstracts, letters to the editor, as well as secondary analyses of previously published articles.

Data Extraction Two independent reviewers (J.M., L.A.O.) independently selected articles for inclusion, performed critical appraisal, and extracted the data according to a preestablished data collection form. Discrepancies were resolved by reaching a consensus with the senior author (F.R.). The following data were extracted: first author, publication year, country where the investigation took place, study period, study design, method used to diagnose diverticulitis, number of patients, gender, proportion of uncomplicated/complicated diverticulitis, proportion of patients who underwent direct colonic evaluation, source of information used to diagnose colorectal cancer (cancer registry vs direct colonic evaluation), length of follow-up, number of patients diagnosed with colorectal cancer among patients with diverticulitis and among those with uncomplicated/ complicated diverticulitis, number of patients diagnosed with polyps/advanced adenomas/adenomas/hyplerplastic polyps among patients who underwent endoscopy, and number of polyps/advanced adenomas/ adenomas/hyplerplastic polyps found in these patients.

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What You Need to Know Background Recent studies have questioned performing colonoscopy after an episode of diverticulitis, considering the low prevalence of colorectal cancer among patients with acute diverticulitis, notably among those with uncomplicated episode. Findings The authors performed a systematic review and metaanalysis to assess the prevalence of colorectal cancer in patients with acute colon diverticulitis. The pooled prevalence of colorectal cancer was 1.9%. This prevalence was 7.9% and 1.3% in patients with complicated and uncomplicated episodes, respectively. Implications for patient care The present systematic review and meta-analysis demonstrate that the prevalence of colorectal cancer in patients with diverticulitis is 1.9%. Therefore, colonoscopy should be considered after an episode of acute diverticulitis.

Risk of Bias Assessment Two authors (J.M., L.A.O.) performed the critical appraisal of the included studies. Risk of bias of observational studies was assessed by using the Newcastle-Ottawa scale. Briefly, the scale consists of 8 multiple-choice questions that address the selection of the study population, the comparability of the study groups, and the method used to assess the outcome. Studies can be awarded a maximum score of 10 points. Studies with 10–8, 7–6, 5–3, and 0–2 points were identified as very good, good, satisfactory, and unsatisfactory, respectively.

Statistical Analysis Prevalences were combined across studies by using random-effects models (Der Simonian and Laird’s approach13). A logit transformation was applied to prevalence before statistical pooling, and the pooled logit of prevalence was then transformed back. The association between the prevalence of colorectal cancer and the presence of complicated/uncomplicated diverticulitis in patients was investigated; the prevalence difference and the ratio of prevalence were combined over studies by using a model with random effects. Some studies reported no colorectal cancer. To avoid their exclusion from the meta-analysis, a treatment arm continuity correction, accounting for unbalanced sample size, was applied.14 To test the robustness of the calculated prevalences, we performed leave-one-out sensitivity analyses (for each study, the pooled estimates were assessed omitting the study). Between-study heterogeneity was

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Figure 1. Flowchart showing selection of publications for review.

assessed by the I2 statistic. To investigate source of heterogeneity, pooled prevalences were compared between studies according to the methods used for outcome measurement, between studies excluding or not of patients not subjected to direct colonic evaluation, excluding or not of patients with complicated diverticulitis, and according to geographical location or length of follow-up. To investigate a potential association between prevalence of colorectal cancer and age, meta-regression analysis was performed by using model with random effects. We further performed sensitivity analyses according to the methodological quality of the included studies. All analyses were performed with the packages Meta and Metafor for R version 3.3.1 (R Foundation for Statistical Computing, Vienna, Austria).15

Results Literature Search and Study Characteristics Four hundred forty-six publications were identified in MEDLINE. Three publications were identified from other sources.16–18 One duplicate study was removed. Of the 448 publications that were identified as eligible, 400 were excluded after title/abstract screening and 17 after full-text screening. Ultimately, 31 publications were included in the qualitative and quantitative synthesis

(Figure 1, Supplementary Table 2).8,16–45 These articles Q4 were recent; 23 were published in the last 5 years.8,19–30,33–38,41,42,45 Nineteen studies were monocentric,8,16–18,20,22,25,26,28,30,31,34,37–39,41–44 eight were multicentric,21,23,24,29,32,33,35,45 and four were population-based.19,27,36,40 Data of 6 studies were prospectively collected,16–18,21,24,29 24 were retrospectively collected,8,19,20,22,23,25,27,28,30–45 and one study did not specify the nature of data collection.26 Two studies included only young patients (<50 years22 and <40 years42). Six publications excluded patients with complicated diverticulitis,16,17,19,29,38,44 twelve studies excluded patients without direct colonic evaluation,16–18,20,21,23–26,33,34,38 and seven studies excluded patients who underwent emergency surgery for diverticulitis.17,20,26,27,34,38,40 According to the NewcastleOttawa scale, 6 studies were ranked as very good,19,23,27,32,35,36 five as good,8,24,30,33,37 twelve as satisfactory,16,17,20,21,25,29,31,34,39,41,44,45 and eight as unsatisfactory18,22,26,28,38,40,42,43 for the studied outcome (Supplementary Table 3).

Prevalence of Colorectal Cancer Thirty-one studies totalling 50,445 patients reported the prevalence of colorectal cancer in diverticulitis patients8,16–45 (Supplementary Table 4). The presence of

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Figure 2. Meta-analysis of prevalence of colorectal cancer among patients with diverticulitis. Forest plot for prevalence of colorectal cancer in patients with diverticulitis. Each horizontal bar summarizes a study. Bars represent 95% CIs. Gray squares inform on each of the studies’ weight in the meta-analysis. Diamond in the lower part of the graph depicts the pooled estimate along with 95% CIs. Events ¼ number of patients with colorectal cancer, total ¼ number of patients included in the meta-analysis.

colorectal cancer was determined by direct colonic evaluation in 20 studies (5273 patients)16–18,20–26,28,29,33,34,38–43 and by consultation of cancer registries in 11 studies (45,172 patients).8,19,27,30–32,35–37,44,45 For the latter studies, the follow-up period in cancer registries was 1 year for 4 studies,19,27,32,35 two years for 1 study,8 and variable for 5 studies.30,31,37,44,45 Data were extracted by the authors at 1 year for 1 study.36 For studies relying on direct colonic evaluation, the proportion of evaluated patients ranged between 34.2%42 and 100%16–18,20,21,23–26,33,34,38 for a median (
standard deviation) proportion of 85.6%
22.4%. The proportion of patients with colorectal cancer ranged between 0%16,18,21,22,30,39,42 and 7.4%23 (Supplementary Table 4). The pooled prevalence of colorectal cancer was 1.9% (95% confidence interval [CI], 1.5%–2.3%; I2, 57%) (Figure 2). This pooled prevalence was robust according to leave-one-out analysis (Supplementary Table 5). Statistical heterogeneity was assessed by performing sensitivity analyses (Tables 1 and 2). The prevalence of colorectal cancer was similar between studies based on cancer registries and those based on direct colonic evaluation (P ¼ .48). Similarly, no significant difference was found between studies excluding or not patients without direct colonic evaluation (P ¼ .25) or complicated diverticulitis (P ¼ .09), as well as between studies with different geographical locations (P ¼ .63) or lengths of follow-up (P ¼ .55)

(Table 1). We noted that prevalences of colorectal cancer did not differ between studies performed in Western versus Asian countries. Furthermore, we performed sensitivity analyses according to the methodological quality of the included studies based on the NewcastleOttawa scale. By pooling only very good and good studies or very good, good, and satisfactory studies, the pooled prevalences of colorectal cancer were similar: 2.0% (95% CI, 1.5%–2.8%; I2, 69.4%) and 2.0% (95% CI, 1.6%–2.5%; I2, 61.7%), respectively (Table 2). By restricting the meta-analysis to studies including >200 patients, the pooled prevalence of colorectal cancer was 1.9% (95% CI, 1.5%–2.3%; I2, 57.0%). To investigate a potential association between prevalence of colorectal cancer and mean (or median) age, we performed a metaregression analysis (model with random effects). The association was not statistically significant (P ¼ .77). The prevalence of colorectal cancer was markedly higher in patients with complicated diverticulitis (46 cancers for 641 patients; prevalence, 7.9%; 95% CI, 3.9%–15.3%; I2, 77%) (Supplementary Table 4, Figure 3B) than in patients with uncomplicated diverticulitis (42 cancers for 3834 patients; prevalence, 1.3%; 95% CI, 0.1%–2%; I2, 40%) (Supplementary Table 4, Figure 3A). These pooled prevalences were robust according to leave-one-out sensitivity analysis (Supplementary Table 6). Statistical heterogeneity for patients with uncomplicated diverticulitis was assessed by performing sensitivity analyses. The prevalence of

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Table 1. Subgroup Comparisons for Prevalence of Colorectal Cancer Subgroup analysis for patients with diverticulitis Outcome measurement Exclusion of patients not subjected to direct colonic evaluation Exclusion of patients with complicated diverticulitis Geographic location

Length of follow-up (mo)

Studies (n)

Registry Direct colonic evaluation Yes No Yes No Europe, Israel, and United States Asia Oceania Short (<6) Intermediate (3–6) Long (>6)

colorectal cancer among those patients was similar between studies based on cancer registries and those based on direct colonic evaluation (P ¼ .17, not shown). The prevalence was 1.1% (95% CI, 0.6%–2.1%; I2, 63.9%) by pooling only studies including >200 patients. Then, we performed sensitivity analyses according to the methodological quality of the included studies based on the Newcastle-Ottawa scale by separately pooling studies reporting the proportion of colorectal cancer in patients with uncomplicated diverticulitis (15 studies,8,16,17,19,20,22,23,29,30,34,35,38,39,41,44 3834 patients) and complicated diverticulitis (9 studies,8,20,22,23,30,34,35,39,41 641 patients) (Table 3). Nine studies8,20,23,30,34,35,39,41,44 reported the numbers of colorectal cancer in both patients with complicated and uncomplicated diverticulitis. Therefore, we calculated the pooled prevalence difference of having colorectal cancer between patients with complicated and uncomplicated diverticulitis and obtained a pooled prevalence difference of 4.1% (95% CI, 0.9%–7.3%; I2, 86.7%; P ¼ .0116) (Figure 3C). Then, we calculated the pooled prevalence ratio to assess the association between colorectal cancer and complicated or uncomplicated diverticulitis. Three of the 9 studies reported no

11 20 12 19 6 25 25 3 3 8 5 7

Pooled prevalence, % (95% CI) 2.0 1.7 2.3 1.6 1.3 2.0 1.9 1.7 1.2 1.6 1.9 2.0

(1.6–0.2.5) (1.1–2.5) (1.4–3.7) (1.3–2.1) (0.8–2.0) (1.6–0.2.5) (1.5–2.3) (0.18–14.37) (0.5–2.9) (1.1–2.2) (0.9–4.1) (1.6–2.5)

P value .48 .25 .09 .63

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colorectal cancer.23,30,39 The pooled prevalence ratio was 6.72 (95% CI, 2.47–18.25; I2, 56.1%; P ¼ .0197) in favor of patients with complicated diverticulitis (Figure 3D).

Prevalence of Polyps, Advanced Adenomas, Adenomas, and Hyperplastic Polyps Twenty-three studies reported the number of diverticulitis patients with polyps8,16,17,20–22,24–26,28–30,32–34,37–39,41–45 (Supplementary Table 7). Among these studies, 2 did not report the number of patients who underwent endoscopy and were therefore excluded from analysis.26,29 The pooled prevalence of polyp was 22.7% (95% CI, 19.6%–26.0%; I2, 85%; 21 studies,8,16,17,20–22,24,25,28,30,32–34,37–39,41–45 4934 patients) (Supplementary Figure 1A). Of note, the proportion of patients with polyps ranged from 5.8%16 to 38.7%,24 therefore resulting in marked heterogeneity in the measure of the pooled prevalence. Seven studies reported the number of patients with advanced adenoma for a total of 1917 patients evaluated by endoscopy20,23,24,30,33,41,43,44 Q5 (Supplementary Table 8). The pooled prevalence of advanced adenoma was 4.4% (95% CI, 3.4%–5.8%; I2,

Table 2. Sensitivity Analysis for Prevalence of Colorectal Cancer, Polyp, Advanced Adenoma, Adenoma, and Hyperplastic Polyp According to the Newcastle-Ottawa Scale All studies

Outcome Adenocarcinoma Polyp Advanced adenoma Adenoma Hyperplastic polyp

Very good and good studies

Very good, good, and satisfactory studies

Studies (n)

Pooled prevalence, % (95% CI)

I2 (%)

Studies (n)

Pooled prevalence, % (95% CI)

I2 (%)

Studies (n)

Pooled prevalence, % (95% CI)

I2 (%)

31 21 8

1.9 (1.5–2.3) 22.7 (19.6–26.0) 4.4 (3.4–5.8)

57.1 84.6 28.8

11 6 4

2.0 (1.5–2.8) 28.2 (22.8–34.4) 3.7 (2.2–6.0)

69.4 84.7 44.9

23 16 7

2.0 (1.6–2.5) 23.8 (20.4–27.6) 4.7 (3.7–6.1)

61.7 83.8 20.8

15 13

14.2 (11.8–17.1) 9.2 (7.6–11.2)

80.4 58.6

6 4

17.8 (12.7–24.4) 11.2 (9.3–13.3)

87.0 0.0

12 11

15.5 (12.7–18.7) 9.0 (7.4–10.9)

80.0 53.5

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Figure 3. Meta-analysis of prevalence of colorectal cancer among patients with uncomplicated or complicated diverticulitis. (A) Forest plot for prevalence of colorectal cancer in patients with uncomplicated diverticulitis and forest plot for prevalence of colorectal cancer in patients with complicated diverticulitis. (B) Forest plot for prevalence difference of colorectal cancer between complicated and uncomplicated diverticulitis and forest plot for prevalence ratio between colorectal cancer and complicated/uncomplicated diverticulitis. Each horizontal bar summarizes a study. Bars represent 95% CIs. Gray squares inform on each of the studies’ weight in the meta-analysis. Diamond in the lower part of the graph depicts the pooled estimate along with 95% CIs. Events ¼ number of patients with colorectal cancer, total ¼ number of patients included in the metaanalysis. CD, complicated diverticulitis; UD, uncomplicated diverticulitis.

29%) (Supplementary Figure 1B). Fifteen studies (3773 patients) reported the number of patients with adenomas among patients who underwent endoscopy8,20,23–25,30,33,34,37,40–45 (Supplementary Table 9). The pooled prevalence of adenoma was 14.2% (95% CI, 11.7%–17.1%; I2, 80%) (Supplementary Figure 1C). Fourteen studies (2938 patients) reported the number of patients with hyperplastic polyp among patients with

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endoscopy8,17,20,25,30,33,34,37,41–45 (Supplementary Q6 Table 10). The pooled prevalence of hyperplastic polyp was 9.2% (95% CI, 7.6%–11.2%; I2, 59%) (Supplementary Figure 1D). All pooled prevalences were robust according to leave-one-out analyses (Supplementary Tables 11–14). Sensitivity analyses for the quality of included studies according to the Newcastle-Ottawa scale are reported in Table 3.

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Table 3. Sensitivity Analysis for Prevalence of Colorectal Cancer Among Patients With Uncomplicated or Complicated 697 Diverticulitis According to the Newcastle-Ottawa Scale 698 699 Very good, good, and 700 All studies Very good and good studies satisfactory studies 701 Pooled Pooled Pooled 702 prevalence, I2 prevalence, I2 prevalence, I2 Studies Studies Studies 703 % (95% CI) % (95% CI) % (95% CI) (%) (n) (%) (n) (%) Population (n) 704 705 Diverticulitis 31 1.9 (1.5–2.3) 57.1 11 2.0 (1.5–2.8) 69.4 23 2.0 (1.6–2.5) 61.7 706 Uncomplicated 15 1.3 (0.8–2.0) 40.4 5 1.2 (0.5–2.7) 42.4 13 1.1 (0.6–2.0) 48.6 707 diverticulitis Complicated diverticulitis 9 7.9 (3.9–15.3) 77.1 4 8.7 (2.3–27.3) 86.0 8 8.2 (3.9–6.2) 79.6 708 709 710 711 712 Twelve studies (2018 patients) reported the total studies on patients with complicated diverticulitis who 713 number of polyps among patients who underwent required emergency surgery). More importantly, because 714 endoscopy16,17,19,21,22,24,33,37,39,41,42,44 (Supplementary of the recent interest in this research question, a majority 715 Table 7). The pooled number of polyps per patient was of the studies included in our meta-analysis were pub716 0.29 (95% CI, 0.17–0.44; I2, 97%) (Supplementary lished after the work by Sharma et al, allowing us to 717 Figure 2A). Two studies totalling 508 patients reported report more precise estimates. 718 the number of advanced adenomas24,39 (Supplementary Among patients who underwent endoscopy, we found 719 Table 8), with a pooled number of advanced adenomas a pooled prevalence of polyps of 22.7%. The proportion 720 per patient of 0.06 (95% CI, 0.05–0.09; I2, 0%) of patients with polyps among the 4934 patients with 721 (Supplementary Figure 2B). Six studies accounting diverticulitis and subsequent endoscopy ranged from 722 for 1310 patients reported the number of ade- 5.8%16 to 38.7%,24 therefore resulting in significant 723 nomas17,19,24,33,37,39 (Supplementary Table 9). The heterogeneity. The pooled prevalences of adenoma and 724 pooled number of adenomas per patient was 0.17 hyperplastic polyps were 14.2% and 9.2%, respectively. 725 (95% CI, 0.10–0.27; I2, 93%) (Supplementary Figure 2C). It is noteworthy that the pooled prevalence of advanced 726 Five studies (906 patients) reported the number of adenoma was 4.4%, which contributes to an increased 727 hyperplastic polyps17,19,24,37,39 (Supplementary Table 10). prevalence of advanced colorectal neoplasia, further 728 The pooled number of hyperplastic polyps per patient supporting that routine endoscopy should be proposed 729 was 0.09 (95% CI, 0.04–0.21; I2, 93%) (Supplementary after an episode of diverticulitis. 730 Some authors support, not without controversy,49 Figure 2D). Of note, all pooled estimates were robust 731 according to leave-one-out analyses (Supplementary that diverticulosis may constitute by itself a risk factor 732 Tables 11–14). for the development of colorectal cancer. For instance, 733 Granlund et al50 performed a case-control study that 734 compared 41,037 patients with colorectal cancer with Discussion 735 82,074 patients without colorectal cancer and assessed 736 whether these patients had been hospitalized for diver737 In the present meta-analysis of observational studies, ticular disease. They found that the odd ratios of colo738 we pooled a large number of patients with diverticulitis rectal cancer ranged between 22.75 and 31.49 six 739 and estimated an overall prevalence of colorectal cancer months after hospitalization for diverticular disease. 740 of 1.9%. Our results also indicate that patients with Importantly, they showed that the risk of colorectal 741 complicated diverticulitis are more than 6-fold more cancer decreased and reached the risk of controls after 742 likely to have colorectal cancer than patients with 12 months after hospitalization. Moreover, radiologic 743 uncomplicated diverticulitis. To date, 3 systematic re- findings, mostly related to complicated diverticulitis, 744 Q7 views of the literature46–48 and 1 meta-analysis9 were were identified as predictors of cancer.7–9,32 Therefore, 745 published on the subject. The meta-analysis by Sharma we believe that the increased risk of cancer observed in 746 et al9 included 11 studies (1970 patients) who under- the acute period after diverticulitis may result from the 747 went endoscopy after an episode of diverticulitis and difficulties in distinguishing diverticulitis from colorectal 748 reported a pooled prevalence of colorectal cancer of cancer on computed tomography, especially in patients 749 1.6%. However, one should note that our systematic re- with complicated diverticulitis, resulting in misdiagnosis. 750 The strengths of this meta-analysis include the large view differs from this previous meta-analysis in at least 2 751 aspects. First, whereas Sharma et al focused on studies number of patients retained in the quantitative synthesis, 752 using endoscopy as a diagnostic technique, we applied the inclusion of studies reporting on cases of cancer 753 wider inclusion criteria and considered population-based identified at the time of emergency surgery for mis754 studies19,27,36,40 (for instance, we retained in the analysis diagnosed complicated diverticulitis, and its clinically

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relevant messages. But there are shortcomings to this meta-analysis, which mostly depend on the characteristics of included publications. First, several included studies were of retrospective design (raising the possibility of bias) and/or were classified as methodologically unsatisfactory for the outcome of interest. However, exclusion of the latest from analysis did not impact the pooled prevalence of colorectal cancer. Second, there was heterogeneity in the statistical analyses, most likely reflecting clinical variability in the design of the included studies and the differences in the studied populations. To this end, all analyses were performed by using randomeffects models, and heterogeneity was investigated through sensitivity analyses, notably with leave-one-out analyses. This latter approach suggested that the reported results were robust even though heterogeneous. Third, calculations of the pooled prevalence difference and prevalence ratio between patients with uncomplicated and complicated diverticulitis were not adjusted. Finally, in this meta-analysis, we could not directly compare the prevalence of colorectal cancer in patients with diverticulitis with the prevalence in reference populations. However, although this remains a matter of debate, evidence from 2 of the included studies indicated that the prevalence of colorectal carcinoma was significantly more elevated than that of the general population.35,36 For instance, in a previous work,35 our team found a prevalence of colorectal cancer 44-fold higher in patients with diverticulitis than in the reference population matched for age and gender. On the basis of these observations, we believe that the prevalence of colorectal cancer is clinically relevant in patients with diverticulitis and higher than the prevalence documented in both screened (prevalence of 0.78%)51 and general populations (age-adjusted incidence rate of 0.046% according to data from the National Cancer Institute’s SEER).52 In conclusion, in this large meta-analysis, the pooled prevalence of colorectal cancer among patients with diverticulitis was 1.9%. We demonstrated that the prevalence of colorectal cancer was significantly higher in patients with complicated diverticulitis than in patients with uncomplicated diverticulitis.

Supplementary Material Note: To access the supplementary material accompanying this article, visit the online version of Clinical Gastroenterology and Hepatology at www.cghjournal.org, and at https://doi.org/10.1016/j.cgh.2018.07.031.

References 1. Masoomi H, Buchberg BS, Magno C, et al. Trends in diverticulitis management in the United States from 2002 to 2007. Arch Surg 2011;146:400–406. 2. Klarenbeek BR, de Korte N, van der Peet DL, et al. Review of current classifications for diverticular disease and a

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translation into clinical practice. Int J Colorectal Dis 2012; 27:207–214. 3. Ben Yaacoub I, Boulay-Coletta I, Julles MC, et al. CT findings of misleading features of colonic diverticulitis. Insights Imaging 2011;2:69–84. 4. Stollman N, Smalley W, Hirano I, et al. American Gastroenterological Association Institute guideline on the management of acute diverticulitis. Gastroenterology 2015;149:1944–1949. 5. Feingold D, Steele SR, Lee S, et al. Practice parameters for the treatment of sigmoid diverticulitis. Dis Colon Rectum 2014; 57:284–294. 6. Westwood D, Eglinton T, Frizelle F. Routine colonoscopy following acute uncomplicated diverticulitis. Br J Surg 2011; 98:1630–1634. 7. Brar MS, Roxin G, Yaffe PB, et al. Colonoscopy following nonoperative management of uncomplicated diverticulitis may not be warranted. Dis Colon Rectum 2013;56:1259–1264. 8. Sallinen V, Mentula P, Leppaniemi A. Risk of colon cancer after computed tomography-diagnosed acute diverticulitis: is routine colonoscopy necessary? Surg Endosc 2014; 28:961–966. 9. Sharma P, Eglinton T, Hider P, et al. Systematic review and meta-analysis of the role of routine colonic evaluation after radiologically confirmed acute diverticulitis. Ann Surg 2014; 259:263–272. 10. Schout P, Spillenaar Bilgen E, Groenen M. Routine screening for colon cancer after conservative treatment of diverticulitis. Dig Surg 2012;29:408–411. 11. ASGE Standards of Practice Committee, Fisher DA, Maple JT, et al. Complications of colonoscopy. Gastrointest Endosc 2011; 74:745–752. 12. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting—Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000;283:2008–2012. 13. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177–188. 14. Sweeting MJ, Sutton AJ, Lambert PC. What to add to nothing? use and avoidance of continuity corrections in meta-analysis of sparse data. Stat Med 2004;23:1351–1375. 15. Viechtbauer W. Conducting meta-analyses in R with the metafor package. Journal of Statistical Software 2010;36:1–48. 16. Lahat A, Yanai H, Menachem Y, et al. The feasibility and risk of early colonoscopy in acute diverticulitis: a prospective controlled study. Endoscopy 2007;39:521–524. 17. Sakhnini E, Lahat A, Melzer E, et al. Early colonoscopy in patients with acute diverticulitis: results of a prospective pilot study. Endoscopy 2004;36:504–507. 18. Hjern F, Jonas E, Holmstrom B, et al. CT colonography versus colonoscopy in the follow-up of patients after diverticulitis: a prospective, comparative study. Clin Radiol 2007;62:645–650. 19. Alexandersson BT, Hreinsson JP, Stefansson T, et al. The risk of colorectal cancer after an attack of uncomplicated diverticulitis. Scand J Gastroenterol 2014;49:576–580. 20. Andrade P, Ribeiro A, Ramalho R, et al. Routine colonoscopy after acute uncomplicated diverticulitis: challenging a putative indication. Dig Surg 2017;34:197–202. 21. Chabok A, Smedh K, Nilsson S, et al. CT-colonography in the follow-up of acute diverticulitis: patient acceptance and diagnostic accuracy. Scand J Gastroenterol 2013; 48:979–986.

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22. Chan DKH, Tan KK. There is no role for colonoscopy after diverticulitis among Asian patients less than 50 years of age. Gastrointest Tumors 2017;3:136–140. 23. Choi YH, Koh SJ, Kim JW, et al. Do we need colonoscopy following acute diverticulitis detected on computed tomography to exclude colorectal malignancy? Dig Dis Sci 2014; 59:2236–2242. 24. Daniels L, Unlu C, de Wijkerslooth TR, et al. Yield of colonoscopy after recent CT-proven uncomplicated acute diverticulitis: a comparative cohort study. Surg Endosc 2015; 29:2605–2613. 25. Elmi A, Hedgire SS, Pargaonkar V, et al. Is early colonoscopy beneficial in patients with CT-diagnosed diverticulitis? AJR Am J Roentgenol 2013;200:1269–1274. 26. Flor N, Maconi G, Sardanelli F, et al. Prognostic value of the diverticular disease severity score based on CT colonography: follow-up in patients recovering from acute diverticulitis. Acad Radiol 2015;22:1503–1509. 27. Grahnat CJ, Herard S, Ackzell A, et al. High probability of an underlying colorectal cancer among patients treated for acute diverticulitis. a population-based cohort follow-up study. World J Surg 2016;40:2283–2288. 28. Horesh N, Saeed Y, Horesh H, et al. Colonoscopy after the first episode of acute diverticulitis: challenging management paradigms. Tech Coloproctol 2016;20:383–387. 29. Isacson D, Thorisson A, Andreasson K, et al. Outpatient, nonantibiotic management in acute uncomplicated diverticulitis: a prospective study. Int J Colorectal Dis 2015;30:1229–1234. 30. Kim MJ, Woo YS, Kim ER, et al. Is colonoscopy necessary after computed tomography diagnosis of acute diverticulitis? Intest Res 2014;12:221–228. 31. Lam TJ, Meurs-Szojda MM, Gundlach L, et al. There is no increased risk for colorectal cancer and adenomas in patients with diverticulitis: a retrospective longitudinal study. Colorectal Dis 2010;12:1122–1126. 32. Lau KC, Spilsbury K, Farooque Y, et al. Is colonoscopy still mandatory after a CT diagnosis of left-sided diverticulitis: can colorectal cancer be confidently excluded? Dis Colon Rectum 2011;54:1265–1270. 33. Lecleire S, Nahon S, Alatawi A, et al. Diagnostic impact of routine colonoscopy following acute diverticulitis: a multicenter study in 808 patients and controls. United European Gastroenterol J 2014;2:301–306.

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conservatively treated patients? J Clin Gastroenterol 2016; 50:e35–e39. 39. Schmilovitz-Weiss H, Yalunin E, Boaz M, et al. Does a colonoscopy after acute diverticulitis affect its management? a single center experience. J Clin Gastroenterol 2012;46:317–320. 40. Schout PJ, Spillenaar Bilgen EJ, Groenen MJ. Routine screening for colon cancer after conservative treatment of diverticulitis. Dig Surg 2012;29:408–411. 41. Suhardja TS, Norhadi S, Seah EZ, et al. Is early colonoscopy after CT-diagnosed diverticulitis still necessary? Int J Colorectal Dis 2017;32:485–489. 42. Syed U, Companioni R, Bansal R, et al. Diverticulitis in the young population: reconsidering conventional recommendations. Acta Gastroenterol Belg 2016;79:435–439. 43. van de Wall BJ, Reuling EM, Consten EC, et al. Endoscopic evaluation of the colon after an episode of diverticulitis: a call for a more selective approach. Int J Colorectal Dis 2012; 27:1145–1150. 44. Westwood DA, Eglinton TW, Frizelle FA. Routine colonoscopy following acute uncomplicated diverticulitis. Br J Surg 2011; 98:1630–1634. 45. Zaman S, Chapman W, Mohammed I, et al. Patients with computed tomography-proven acute diverticulitis require follow-up to exclude colorectal cancer. Intest Res 2017; 15:195–202. 46. Daniels L, Unlu C, de Wijkerslooth TR, et al. Routine colonoscopy after left-sided acute uncomplicated diverticulitis: a systematic review. Gastrointest Endosc 2014;79:378–389, quiz 498–498 e5. 47. de Vries HS, Boerma D, Timmer R, et al. Routine colonoscopy is not required in uncomplicated diverticulitis: a systematic review. Surg Endosc 2014;28:2039–2047. 48. Sai VF, Velayos F, Neuhaus J, et al. Colonoscopy after CT diagnosis of diverticulitis to exclude colon cancer: a systematic literature review. Radiology 2012;263:383–390. 49. Morini S, Zullo A, Hassan C, et al. Diverticulosis and colorectal cancer: between lights and shadows. J Clin Gastroenterol 2008; 42:763–770. 50. Granlund J, Svensson T, Granath F, et al. Diverticular disease and the risk of colon cancer: a population-based case-control study. Aliment Pharmacol Ther 2011;34:675–681. 51. Niv Y, Hazazi R, Levi Z, et al. Screening colonoscopy for colorectal cancer in asymptomatic people: a meta-analysis. Dig Dis Sci 2008;53:3049–3054.

34. Meireles LC, Fernandes SR, Ribeiro LC, et al. Role of endoscopy after an acute episode of diverticulitis: analysis of a cohort of Portuguese patients from a tertiary referral center. Eur J Gastroenterol Hepatol 2015;27:1429–1432.

52. Ansa BE, Coughlin SS, Alema-Mensah E, et al. Evaluation of colorectal cancer incidence trends in the United States (2000-2014). J Clin Med 2018;7:22.

35. Meyer J, Thomopoulos T, Usel M, et al. The incidence of colon cancer among patients diagnosed with left colonic or sigmoid acute diverticulitis is higher than in the general population. Surg Endosc 2015;29:3331–3337.

53. Brenner H, Hoffmeister M, Stegmaier C, et al. Risk of progression of advanced adenomas to colorectal cancer by age and sex: estimates based on 840,149 screening colonoscopies. Gut 2007;56:1585–1589.

36. Mortensen LQ, Burcharth J, Andresen K, et al. An 18-year nationwide cohort study on the association between diverticulitis and colon cancer. Ann Surg 2017;265:954–959. 37. Ou G, Rosenfeld G, Brown J, et al. Colonoscopy after CTdiagnosed acute diverticulitis: is it really necessary? Can J Surg 2015;58:226–231. 38. Ramphal W, Schreinemakers JM, Seerden TC, et al. What is the risk of colorectal cancer after an episode of acute diverticulitis in

Reprint requests Address requests for reprints to: Jeremy Meyer, MD, PhD, Division of Digestive and Transplantation Surgery, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, 1211 Genève 14, Switzerland. e-mail: jeremy.meyer@ hcuge.ch; fax: ---. Conflicts of interest The authors disclose no conflicts.

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Supplementary Figure 1. Metaanalysis of prevalence of polyps, advanced adenomas, adenomas, and hyperplastic polyps among patients with diverticulitis. (A) Forest plot for prevalence of patients with polyps. (B) Forest plot for prevalence of patients with advanced adenomas. (C) Forest plot for prevalence of patients with adenomas. (D) Forest plot for prevalence of patients with hyperplastic polyps. Each horizontal bar summarizes a study. Prevalences for each study were calculated by determining the number of patients with polyps, advanced adenomas, adenomas, or hyperplastic polyps among patients who received endoscopy. Bars represent 95% CIs. Gray squares inform on each of the studies’ weight in the meta-analysis. Diamond in the lower part of the graph depicts the pooled estimate along with 95% CIs. Advanced adenomas were defined as adenomas 10 mm and/or with villous component and/or with high-grade dysplasia.53

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Supplementary Figure 2. Meta-analysis of number of polyps, advanced adenomas, adenomas, and hyperplastic polyps among patients with diverticulitis. (A) Forest plot for number of polyps per patient. (B) Forest plot for number of advanced adenomas per patient. (C) Forest plot for number of adenomas per patient. (D) Forest plot for number of hyperplastic polyps per patient. Each horizontal bar summarizes a study. Bars represent 95% CIs. Gray squares inform on each of the studies’ weight in the meta-analysis. Diamond in the lower part of the graph depicts the pooled estimate along with 95% CIs.

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Supplementary Table 1. Checklist for Meta-analysis of Observational Studies in Epidemiology (MOOSE) Item no.

Recommendation

Reporting of background includes 1 Problem definition 2 Hypothesis statement 3 Description of study outcome(s) 4 Type of exposure or intervention used 5 Type of study designs used 6 Study population Reporting of search strategy includes 7 Qualifications of searchers (eg, librarians and investigators) 8 Search strategy, including time period included in the synthesis and key words 9 Effort to include all available studies, including contact with authors 10 Databases and registries searched 11 Search software used, name and version, including special features used (eg, explosion) 12 Use of hand searching (eg, reference lists of obtained articles) 13 List of citations located and those excluded, including justification 14 Method of addressing articles published in languages other than English 15 Method of handling abstracts and unpublished studies 16 Description of any contact with authors Reporting of methods includes 17 Description of relevance or appropriateness of studies assembled for assessing the hypothesis to be tested 18 Rationale for the selection and coding of data (eg, sound clinical principles or convenience) 19 Documentation of how data were classified and coded (eg, multiple raters, blinding and interrater reliability) 20 Assessment of confounding (eg, comparability of cases and controls in studies where appropriate) 21 Assessment of study quality, including blinding of quality assessors, stratification or regression on possible predictors of study results 22 Assessment of heterogeneity 23 Description of statistical methods (eg, complete description of fixed or random effects models, justification of whether the chosen models account for predictors of study results, dose-response models, or cumulative meta-analysis) in sufficient detail to be replicated 24 Provision of appropriate tables and graphics

Reporting of results includes 25 Graphic summarizing individual study estimates and overall estimate 26

Table giving descriptive information for each study included

27 28

Results of sensitivity testing (eg, subgroup analysis) Indication of statistical uncertainty of findings

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Reported on page no. P6 P6 P6 P6 P6 P6 P6 P6 P6 P6 — P6 — — P6 — P7, Supplementary Table 3 P7 P7 — P7, Supplementary Table 3 P7 P7

Figs. 1–3, Supplementary Figs. 1 and 2, Supplementary Tables 1–14 Figs. 2 and 3, Supplementary Figs. 1 and 2 Supplementary Tables 2 and 3, 9–12 Tables 1–3 Figs.1–3, Supplementary Figs. 1 and 2

1335 1336 1337 1338 1339 1340 1341 1342 1343 1344 1345 1346 1347 1348 1349 1350 1351 1352 1353 1354 1355 1356 1357 1358 1359 1360 1361 1362 1363 1364 1365 1366 1367 1368 1369 1370 1371 1372 1373 1374 1375 1376 1377 1378 1379 1380 1381 1382 1383 1384 1385 1386 1387 1388 1389 1390 1391 1392

1393 1394 1395 1396 1397 1398 1399 1400 1401 1402 1403 1404 1405 1406 1407 1408 1409 1410 1411 1412 1413 1414 1415 1416 1417 1418 1419 1420 1421 1422 1423 1424 1425 1426 1427 1428 1429 1430 1431 1432 1433 1434 1435 1436 1437 1438 1439 1440 1441 1442 1443 1444 1445 1446 1447 1448 1449 1450 -

Supplementary Table 2. Characteristics of Included Studies

Country

Studied period

Monocentric/ multicentric

2014

Iceland

2006–2011

2017

Portugal

07/2008–06/2013

Populationbased Monocentric

Chabok et al

2013

Sweden

10/2005–01/2007

Multicentric

Chan et al

2017

Singapore

01/2012–06/2014

Monocentric

Choi et al

2014

South Korea

01/2001–03/2013

Multicentric

Daniels et al

2015

The Netherlands

06/2010–04/2013

Multicentric

Elmi et al

2013

01/2000–12/2004

Monocentric

Flor et al

2015

United States of America Italy

03/2010–12/2013

Monocentric

Grahnat et al

2016

Sweden

2005–2011

Hjern et al

2007

Sweden

07/2002–08/2004

Populationbased Monocentric

Horesh et al

2016

Israel

01/2008–12/2012

Monocentric

Isacson et al

2015

Sweden

Kim et al

2014

South Korea

Lahat et al

2007

Israel

01/2004–06/2006

Monocentric

Lam et al

2010

The Netherlands

1990–2000

Monocentric

Lau et al

2011

Australia

01/2003–06/2009

Multicentric

Lecleire et al

2014

France

01/2005–12/2011

Multicentric

Meireles et al

2015

Portugal

01/2004–12/2013

Monocentric

Meyer et al

2015

Switzerland

01/2005–12/2009

Multicentric

Mortensen et al

2017

Denmark

01/2000–01/2013

Ou et al

2015

Canada

12/2005–12/2010

Populationbased Monocentric

03/2012–12/2013 and 05/2012–08/2012 11/1994–12/2011

Multicentric Monocentric

Method of diagnosis

Retrospective cohort Retrospective cohort Prospective cohort Retrospective cohort Retrospective cohort Prospective cohort Retrospective cohort Cohort

CT

Yes

No

No

CT

No

Yes

Yes

CT

No

Yes

.

CT

No

No

No

CT

No

Yes

.

CT

No

Yes

No

CT

No

Yes

.

CT

No

Yes

Yes

No

No

Yes

No

Yes

No

No

No

Yes

Yes

No

No

No

No

No

Yes

Yes

No

No

No

No

Retrospective CT cohort Prospective Variable cohort Retrospective CT cohort Prospective CT cohort Retrospective CT cohort Prospective CT cohort Retrospective CT and/or cohort surgery Retrospective CT cohort Retrospective CT cohort Retrospective CT and/or US cohort Retrospective CT cohort Retrospective . cohort CT

Registry

1y

Direct colonic 16
11.4 evaluation wk Direct colonic 6–8 wk evaluation Direct colonic . evaluation Direct colonic <1 y evaluation Direct colonic 55 days evaluation Direct colonic 6 mo evaluation Direct colonic 9
7 wk evaluation Registry 1y Direct colonic evaluation Direct colonic evaluation Direct colonic evaluation Registry

85 days 3.25 mo 3 mo 66 mo

No

Direct colonic evaluation Registry

. 12 y

No

No

Registry

1y

No

Yes

No

6 mo

No

Yes

Yes

4 mo

No

No

No

Direct colonic evaluation Direct colonic evaluation Registry

No

No

No

Registry

1y

No

No

No

Registry

1y

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Cancer Exclusion of Exclusion if no outcome Followcomplicated direct colonic Exclusion up evaluation if surgery measurement diverticulitis

Study design

2018

Study

Year of publication

9.e4

1451 1452 1453 1454 1455 1456 1457 1458 1459 1460 1461 1462 1463 1464 1465 1466 1467 1468 1469 1470 1471 1472 1473 1474 1475 1476 1477 1478 1479 1480 1481 1482 1483 1484 1485 1486 1487 1488 1489 1490 1491 1492 1493 1494 1495 1496 1497 1498 1499 1500 1501 1502 1503 1504 1505 1506 1507 1508

1509 1510 1511 1512 1513 1514 1515 1516 1517 1518 1519 1520 1521 1522 1523 1524 1525 1526 1527 1528 1529 1530 1531 1532 1533 1534 1535 1536 1537 1538 1539 1540 1541 1542 1543 1544 1545 1546 1547 1548 1549 1550 1551 1552 1553 1554 1555 1556 1557 1558 1559 1560 1561 1562 1563 1564 1565 1566 9.e5

Supplementary Table 2. Continued

Country

Studied period

Monocentric/ multicentric

2016

The Netherlands

01/2008–07/2013

Monocentric

Sakhnini et al

2004

Israel

07/2000–01/2003

Monocentric

Sallinen et al

2013

Finland

2006–2010

Monocentric

SchmilovitzWeiss et al Schout et al

2012

Israel

06/2002–09/2009

Monocentric

2012

The Netherlands

2000–2010

Suhardja et al

2017

Australia

2011–2013

Populationbased Monocentric

Syed et al

2016

2007–2015

Monocentric

van de Wall et al Westwood et al

2012

United States of America The Netherlands

01/2007–01/2010

Monocentric

2011

New Zealand

01/2004–12/2008

Monocentric

Zaman et al

2017

United Kingdom

10/2007–03/2014

Multicentric

Method of diagnosis

Retrospective cohort Retrospective CT and/or US cohort Prospective CT cohort CT Retrospective cohort Retrospective CT cohort Retrospective . cohort Retrospective CT cohort Retrospective CT cohort Retrospective CT and/or US cohort Retrospective CT cohort Retrospective CT cohort

Exclusion of Exclusion if no Cancer complicated direct colonic Exclusion outcome Followdiverticulitis evaluation if surgery measurement up

Yes

Yes

Yes

Yes

Yes

Yes

No

No

No

No

No

No

No

No

Partially

No

No

No

No

No

No

No

No

No

Yes

No

No

No

No

No

February 2014 Direct colonic 6 wk–3 mo evaluation Direct colonic 5.8 days evaluation Registry 2y Direct colonic 4 wk–26 evaluation mo Direct colonic 6–10 wk evaluation Direct colonic 1y evaluation Direct colonic . evaluation Direct colonic 6 mo evaluation Registry December 2009 Registry .

NOTE. Direct colonic evaluation included endoscopy (colonoscopy and sigmoidoscopy), computed colonographies, and barium enema. CT, computed tomography; US, ultrasonography.

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Meyer et al

Study

Year of publication

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No. -

1567 1568 1569 1570 1571 1572 1573 1574 1575 1576 1577 1578 1579 1580 1581 1582 1583 1584 1585 1586 1587 1588 1589 1590 1591 1592 1593 1594 1595 1596 1597 1598 1599 1600 1601 1602 1603 1604 1605 1606 1607 1608 1609 1610 1611 1612 1613 1614 1615 1616 1617 1618 1619 1620 1621 1622 1623 1624

-

1625 1626 1627 1628 1629 1630 1631 1632 1633 1634 1635 1636 1637 1638 1639 1640 1641 1642 1643 1644 1645 1646 1647 1648 1649 1650 1651 1652 1653 1654 1655 1656 1657 1658 1659 1660 1661 1662 1663 1664 1665 1666 1667 1668 1669 1670 1671 1672 1673 1674 1675 1676 1677 1678 1679 1680 1681 1682

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9.e6

Supplementary Table 3. Critical Appraisal of the Included Studies According to the Newcastle-Ottawa Scale Selection

Comparability

Follow-up

Study

A

B

C

D

E

F

G

H

Total

Rating

Alexandersson et al Andrade et al Chabok et al Chan et al Choi et al Daniels et al Elmi et al Flor et al Grahnat et al Hjern et al Horesh et al Isacson et al Kim et al Lahat et al Lam et al Lau et al Lecleire et al Meireles et al Meyer et al Mortensen et al Ou et al Ramphal et al Sakhnini et al Sallinen et al Schmilovitz-Weiss et al Schout et al Suhardja et al Syed et al van de Wall et al Westwood et al Zaman et al

1 1 1 0 1 1 1 1 1 1 1 1 2 1 2 2 1 1 2 2 2 1 1 2 1 1 2 0 1 1 2

1 0 0 0 1 1 0 0 1 0 0 0 0 0 0 1 1 0 1 1 0 0 0 0 0 0 0 0 0 0 0

1 1 1 1 1 1 1 1 1 0 1 1 1 1 1 1 1 0 1 0 1 0 1 1 1 0 1 1 0 1 1

0 0 0 0 1 0 1 0 1 0 0 0 1 0 0 0 1 1 1 0 0 0 0 0 0 1 0 0 0 0 0

2 0 0 0 2 2 0 0 2 0 0 0 0 0 0 1 2 0 2 2 0 0 0 0 0 0 0 0 0 0 0

1 1 1 0 1 1 1 0 1 1 0 1 1 1 1 1 1 1 1 1 1 1 1 1 1 0 0 0 0 1 1

1 1 0 0 1 0 1 0 1 0 0 0 0 0 0 1 0 0 1 1 1 0 0 1 0 0 0 0 0 1 0

1 0 0 0 0 0 0 0 0 0 0 0 1 0 1 1 0 0 1 1 1 0 0 1 0 0 0 0 0 1 1

8 4 3 1 8 6 5 2 8 2 2 3 6 3 5 8 7 3 10 8 6 2 3 6 3 2 3 1 1 5 5

Very good Satisfactory Satisfactory Unsatisfactory Very good Good Satisfactory Unsatisfactory Very good Unsatisfactory Unsatisfactory Satisfactory Good Satisfactory Satisfactory Very good Good Satisfactory Very good Very good Good Unsatisfactory Satisfactory Good Satisfactory Unsatisfactory Satisfactory Unsatisfactory Unsatisfactory Satisfactory Satisfactory

NOTE. Points were allocated as follows: A, representativeness of the exposed cohort: (2) all stages of diverticulitis included, (1) exclusion of subgroups of patients (complicated diverticulitis, surgical cases, patients without endoscopy, patients with hematochezia), (0) exclusion of subgroups of patients based on age; B, selection of the non-exposed cohort : (1): patients without diverticulitis from a colonoscopy screening, in-hospital, or national database, (0) no control group; C, ascertainment of exposure: (1) diverticulitis was diagnosed with computed tomography and/or surgery, (0) other; D, demonstration that the outcome of interest was not present at the beginning of the cohort: (1) patients with history of colorectal carcinoma were excluded, (0) other; E, comparability of cohorts: (2) patients with/without diverticulitis were matched for age and for at least another variable, (1) patients with/without diverticulitis were matched for age, (0) other; F, assessment of outcome: (1) colorectal cancer was looked for in >90% patients using cancer registry and/or endoscopy and/or colon-CT, (0) other; G, length of follow-up: (1) outcome was verified after at least 1 y of follow-up, (0) other; H, adequacy of follow-up: (1) outcome was verified after at least 1 y of follow-up using cancer registry and/or patients contact and/or colonoscopy and/or colon-CT, (0) other. CT, computed tomography.

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1683 1684 1685 1686 1687 1688 1689 1690 1691 1692 1693 1694 1695 1696 1697 1698 1699 1700 1701 1702 1703 1704 1705 1706 1707 1708 1709 1710 1711 1712 1713 1714 1715 1716 1717 1718 1719 1720 1721 1722 1723 1724 1725 1726 1727 1728 1729 1730 1731 1732 1733 1734 1735 1736 1737 1738 1739 1740

1741 1742 1743 1744 1745 1746 1747 1748 1749 1750 1751 1752 1753 1754 1755 1756 1757 1758 1759 1760 1761 1762 1763 1764 1765 1766 1767 1768 1769 1770 1771 1772 1773 1774 1775 1776 1777 1778 1779 1780 1781 1782 1783 1784 1785 1786 1787 1788 1789 1790 1791 1792 1793 1794 1795 1796 1797 1798 9.e7

Supplementary Table 4. Characteristics of Included Studies Regarding Prevalence of Colorectal Cancer UD (n)

UD (%)

282

282

100.00 Excluded Excluded

252 108 55 149 401 402 46 890 50 425 155 177 86 288 1088 404 427 506 40,496 285 645 93 633 200

209 — 42 128 371 — 31 — — 346 155 127 86 . . 363 347 403 — — 645 93 488 186

82.94 — 76.36 85.91 92.52 — 67.39 — — 81.41 100.00 71.75 100.00 . . 89.85 81.26 79.64 — — 100.00 100.00 77.09 93.00

422 523 123 307 292 235

— 351 — 271 292 183

CD (n)

CD (%)

Adenocarcinoma Adenocarcinomaa Adenocarcinoma Adenocarcinoma Adenocarcinoma Adenocarcinoma Q8 (patient, %) in CD (patient, n) in CD (patient, %) in UD (patient, n) in UD (patient, %) (patient, n) 2

0.71

Excluded

Excluded

2

0.71

17.06 — 23.64 14.09 7.48 — 32.61 — — 18.59 Excluded 28.25 Excluded . . 10.15 18.74 20.36 — — Excluded Excluded 22.91 7.00

8 0 0 11 5 8 2 12 0 4 2 0 0 5 23 1 20 11 977 4 10 2 16 0

3.17 0.00 0.00 7.38 1.25 1.99 4.35 1.35 0.00 0.94 1.29 0.00 0.00 1.74 2.11 0.25 4.68 2.17 2.41 1.40 1.55 2.15 2.53 0.00

7 — 0 8 — — — — — — Excluded 0 Excluded . . . 8 3 — — Excluded Excluded 16 0

16.28 — 0.00 38.10 — — — — — — Excluded 0.00 Excluded . . . 10.00 2.91 — — Excluded Excluded 11.03 0.00

1 — 0 3 — — — — — — 2 0 0 . . . 12 8 — — 10 2 0 0

0.48 — 0.00 2.34 — — — — — — 1.29 0.00 0.00 . . . 3.46 1.99 — — 1.55 2.15 0.00 0.00

— — — 67.11 172 32.89 — — — 88.27 36 11.73 100.00 Excluded Excluded 77.87 49 20.85

8 5 0 2 1 5

1.90 0.96 0.00 0.65 0.34 2.13

— 4 — — Excluded —

— 2.33 — — Excluded —

— 1 — — 1 —

— 0.28 — — 0.34 —

43 — 13 21 30 — 15 — — 79 Excluded 50 Excluded . . 41 80 103 — — Excluded Excluded 145 14

NOTE. For analyses, the study by Grahnat et al27 was considered as a cohort study for the measured outcome, including 890 patients, with control population being the population extracted from the Swedish National Board of Health and Welfare used to calculate the standardized incidence ratios. For the study by van de Wall et al,43 we considered data from all 307 patients, including patients without endoscopy who were excluded by the authors, to better assess the population of patients with diverticulitis. Outcome data considered for analysis were extracted at 1 year of follow-up from the study by Mortensen et al.36 CD, complicated diverticulitis; UD, uncomplicated diverticulitis.

Clinical Gastroenterology and Hepatology Vol.

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Alexandersson et al Andrade et al Chabok et al Chan et al Choi et al Daniels et al Elmi et al Flor et al Grahnat et al Hjern et al Horesh et al Isacson et al Kim et al Lahat et al Lam et al Lau et al Lecleire et al Meireles et al Meyer et al Mortensen et al Ou et al Ramphal et al Sakhnini et al Sallinen et al SchmilovitzWeiss et al Schout et al Suhardja et al Syed et al van de Wall et al Westwood et al Zaman et al

Patient (n)

Meyer et al

Study

-,

No. -

1799 1800 1801 1802 1803 1804 1805 1806 1807 1808 1809 1810 1811 1812 1813 1814 1815 1816 1817 1818 1819 1820 1821 1822 1823 1824 1825 1826 1827 1828 1829 1830 1831 1832 1833 1834 1835 1836 1837 1838 1839 1840 1841 1842 1843 1844 1845 1846 1847 1848 1849 1850 1851 1852 1853 1854 1855 1856

-

1857 1858 1859 1860 1861 1862 1863 1864 1865 1866 1867 1868 1869 1870 1871 1872 1873 1874 1875 1876 1877 1878 1879 1880 1881 1882 1883 1884 1885 1886 1887 1888 1889 1890 1891 1892 1893 1894 1895 1896 1897 1898 1899 1900 1901 1902 1903 1904 1905 1906 1907 1908 1909 1910 1911 1912 1913 1914

2018

Colorectal Cancer in Patients With Acute Diverticulitis

Supplementary Table 5. Leave-one-out Sensitivity Analysis for Estimation of Pooled Prevalence of Colorectal Cancer Adenocarcinoma Pooled prevalence (95% CI)

Study omitted Alexandersson et al, 2014 Andrade et al, 2017 Chabok et al, 2013 Chan et al, 2017 Choi et al, 2014 Daniels et al, 2015 Elmi et al, 2013 Flor et al, 2015 Grahnat et al, 2016 Hjern et al, 2007 Horesh et al, 2016 Isacson et al, 2015 Kim et al, 2014 Lahat et al, 2007 Lam et al, 2010 Lau et al, 2011 Lecleire et al, 2014 Meireles et al, 2015 Meyer et al, 2015 Mortensen et al, 2017 Ou et al, 2015 Ramphal et al, 2016 Sakhnini et al, 2004 Sallinen et al, 2013 Schmilovitz-Weiss et al, 2012 Schout et al, 2012 Suhardja et al, 2017 Syed et al, 2016 van de Wall et al, 2012 Westwood et al, 2011 Zaman et al, 2017

0.0193 0.0183 0.0190 0.0189 0.0108 0.0191 0.0187 0.0185 0.0192 0.0189 0.0194 0.0190 0.0191 0.0190 0.0188 0.0184 0.0194 0.0179 0.0186 0.0173 0.0190 0.0109 0.0187 0.0183 0.0191 0.0187 0.0194 0.0190 0.0193 0.0193 0.0187

(0.0156–0.0238) (0.0147–0.0228) (0.0154–0.0235) (0.0153–0.0234) (0.0148–0.0219) (0.0154–0.0237) (0.0150–0.0233) (0.0150–0.0229) (0.0155–0.0239) (0.0153–0.0234) (0.0157–0.0239) (0.0153–0.0235) (0.0155–0.0235) (0.0154–0.0234) (0.0152–0.0234) (0.0147–0.0231) (0.0158–0.0239) (0.0145–0.0220) (0.0149–0.0231) (0.0133–0.0225) (0.0153–0.0236) (0.0153–0.0236) (0.0151–0.0232) (0.0146–0.0229) (0.0155–0.0236) (0.0151–0.0233) (0.0157–0.0240) (0.0154–0.0235) (0.0157–0.0238) (0.0157–0.0238) (0.0150–0.0232)

I2 (%) 56.7 58.1 57.7 58.2 47.6 57.2 58.4 58.1 56.1 58.3 56.4 58.1 57.1 57.9 58.2 58.3 55.2 51.8 58.5 56.9 57.9 57.4 58.5 58.5 56.9 58.3 55.9 57.6 56.4 56.1 58.5

CI, confidence interval.

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9.e8

1915 1916 1917 1918 1919 1920 1921 1922 1923 1924 1925 1926 1927 1928 1929 1930 1931 1932 1933 1934 1935 1936 1937 1938 1939 1940 1941 1942 1943 1944 1945 1946 1947 1948 1949 1950 1951 1952 1953 1954 1955 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 1967 1968 1969 1970 1971 1972

9.e9

1973 1974 1975 1976 1977 1978 1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030

Meyer et al

Clinical Gastroenterology and Hepatology Vol.

-,

No.

-

Supplementary Table 6. Leave-one-out Sensitivity Analyses for Estimation of Pooled Prevalence of Colorectal Cancer Among Patients With Uncomplicated or Complicated Diverticulitis Complicated diverticulitis Study omitted

Pooled prevalence (95% CI)

Andrade et al, 2017 Chan et al, 2017 Choi et al, 2014 Kim et al, 2014 Meireles et al, 2015 Meyer et al, 2015 Sallinen et al, 2013 Schmilovitz-Weiss et al, 2012 Suhardja et al, 2017 Alexandersson et al, 2014 Isacson et al, 2015 Lahat et al, 2007 Ramphal et al, 2016 Sakhnini et al, 2004 Westwood et al, 2011

0.0675 0.0815 0.0629 0.0878 0.0723 0.0908 0.0693 0.0819 0.0980

(0.0296–0.1464) (0.0393–0.1616) (0.0340–0.1137) (0.0435–0.1691) (0.0306–0.1613) (0.0441–0.1781) (0.0277–0.1631) (0.0395–0.1621) (0.0502–0.1824)

Uncomplicated diverticulitis I2 (%) 78.8 79.6 63.0 78.0 79.9 76.1 79.9 79.5 71.1

Pooled prevalence (95% CI) 0.0133 0.0124 0.0116 0.0130 0.0119 0.0111 0.0141 0.0133 0.0140 0.0132 0.0123 0.0128 0.0114 0.0118 0.0137

(0.0084–0.0209) (0.0078–0.0199) (0.0070–0.0189) (0.0082–0.0205) (0.0080–0.0177) (0.0066–0.0188) (0.0093–0.0215) (0.0084–0.0208) (0.0090–0.0216) (0.0083–0.0211) (0.0075–0.0200) (0.0080–0.0203) (0.0067–0.0194) (0.0073–0.0192) (0.0088–0.0214)

CI, confidence interval.

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I2 (%) 40.6 44.5 43.8 42.0 12.2 44.0 33.4 40.3 35.8 40.7 44.4 43.3 44.5 44.4 37.8

2031 2032 2033 2034 2035 2036 2037 2038 2039 2040 2041 2042 2043 2044 2045 2046 2047 2048 2049 2050 2051 2052 2053 2054 2055 2056 2057 2058 2059 2060 2061 2062 2063 2064 2065 2066 2067 2068 2069 2070 2071 2072 2073 2074 2075 2076 2077 2078 2079 2080 2081 2082 2083 2084 2085 2086 2087 2088

-

2089 2090 2091 2092 2093 2094 2095 2096 2097 2098 2099 2100 2101 2102 2103 2104 2105 2106 2107 2108 2109 2110 2111 2112 2113 2114 2115 2116 2117 2118 2119 2120 2121 2122 2123 2124 2125 2126 2127 2128 2129 2130 2131 2132 2133 2134 2135 2136 2137 2138 2139 2140 2141 2142 2143 2144 2145 2146

2018

Colorectal Cancer in Patients With Acute Diverticulitis

9.e10

Supplementary Table 7. Characteristics of Included Studies Regarding Prevalence of Polyps

Study

Patient (n)

Alexandersson 282 et al Andrade et al 252 Chabok et al 108 Chan et al 55 Choi et al 149 Daniels et al 401 Elmi et al 402 Flor et al 46 Grahnat et al 890 Hjern et al 50 Horesh et al 425 Isacson et al 155 Kim et al 177 Lahat et al 86 Lam et al 288 Lau et al 1088 Lecleire et al 404 Meireles et al 427 Meyer et al 506 Mortensen et al 40,496 Ou et al 285 Ramphal et al 645 Sakhnini et al 93 Sallinen et al 633 Schmilovitz200 Weiss et al Schout et al 422 Suhardja et al 523 Syed et al 123 van de Wall 307 et al Westwood et al 292 Zaman et al 235

Direct colonic evaluation (patient, n)

Direct colonic evaluationa (patient, %)

Endoscopy (patient, n)

Endoscopya Polyp Polypb Polyp Polypb (patient, %) (patient, n) (patient, %) (n) (%)

234

82.98

199

70.57

—

—

33

16.58

252 108 27 149 401 402 46 — 50 310 150 61 86 — 319 404 427 — 22,646 114 645 93 394 100

100.00 100.00 49.09 100.00 100.00 100.00 100.00 — 100.00 72.94 96.77 34.46 100.00 — 29.32 100.00 100.00 — 55.92 40.00 100.00 100.00 62.24 50.00

252 108 27 149 401 402 — — 50 310 — 61 86 — 319 404 427 — 22,646 113 645 93 394 100

100.00 100.00 49.09 100.00 100.00 100.00 — — 100.00 72.94 — 34.46 100.00 — 29.32 100.00 100.00 — 55.92 39.65 100.00 100.00 62.24 50.00

68 20 6 — 155 78 8 — — 46 13 19 5 — 82 91 118 — — 34 117 8 94 36

26.98 18.52 22.22 – 38.65 19.40 — — — 14.84 — 31.15 5.81 — 25.71 22.52 27.63 — — 30.09 18.14 8.60 23.86 36.00

— 51 6 — 330 — — — — — 13 — 8 — — 94 — — — 34 — 10 — 48

— 47.22 22.22 — 82.29 — — — — — — — 9.30 — — 23.27 — — — 30.09 — 10.75 — 48.00

381 270 42 205

90.28 51.63 34.15 66.78

378 270 42 205

89.57 51.63 34.15 66.78

— 59 12 38

— 21.85 28.57 18.54

— 59 12 —

— 21.85 28.57 —

205 100

70.21 42.55

175 100

59.93 42.55

50 14

28.57 14.00

50 —

28.57 —

a

Among patients with diverticulitis. Among patients who received endoscopy.

b

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2147 2148 2149 2150 2151 2152 2153 2154 2155 2156 2157 2158 2159 2160 2161 2162 2163 2164 2165 2166 2167 2168 2169 2170 2171 2172 2173 2174 2175 2176 2177 2178 2179 2180 2181 2182 2183 2184 2185 2186 2187 2188 2189 2190 2191 2192 2193 2194 2195 2196 2197 2198 2199 2200 2201 2202 2203 2204

2205 2206 2207 2208 2209 2210 2211 2212 2213 2214 2215 2216 2217 2218 2219 2220 2221 2222 2223 2224 2225 2226 2227 2228 2229 2230 2231 2232 2233 2234 2235 2236 2237 2238 2239 2240 2241 2242 2243 2244 2245 2246 2247 2248 2249 2250 2251 2252 2253 2254 2255 2256 2257 2258 2259 2260 2261 2262 9.e11

Supplementary Table 8. Characteristics of Included Studies Regarding Prevalence of Advanced Adenoma Direct colonic evaluationa (patient, %)

Endoscopy (patient, n)

Endoscopya (patient, %)

Advanced Advanced adenoma adenomab (patient, n) (patient, %)

Advanced adenoma (n)

Advanced adenomab (%)

282

234

82.98

199

70.57

—

—

—

—

252 108 55 149 401 402 46 890 50 425 155 177 86 288 1088 404 427 506 40,496 285 645 93 633 200

252 108 27 149 401 402 46 — 50 310 150 61 86 — 319 404 427 — 22,646 114 645 93 394 100

100.00 100.00 49.09 100.00 100.00 100.00 100.00 — 100.00 72.94 96.77 34.46 100.00 — 29.32 100.00 100.00 — 55.92 40.00 100.00 100.00 62.24 50.00

252 108 27 149 401 402 — — 50 310 — 61 86 — 319 404 427 — 22,646 113 645 93 394 100

100.00 100.00 49.09 100.00 100.00 100.00 — — 100.00 72.94 — 34.46 100.00 — 29.32 100.00 100.00 — 55.92 39.65 100.00 100.00 62.24 50.00

13 — — 5 22 — — — — — — 0 — — — 11 — — — — — — — —

5.16 — — 3.36 5.49 — — — — — — 0.00 — — — 2.72 — — — — — — — —

— — — — 26 — — — — — — — — — — — — — — — — — — 6

— — — — 6.48 — — — — — — — — — — — — — — — — — — 6.00

422 523 123 307 292 235

381 270 42 205 205 100

90.28 51.63 34.15 66.78 70.21 42.55

378 270 42 205 175 100

89.57 51.63 34.15 66.78 59.93 42.55

— 16 — 5 10 —

— 5.93 — 2.44 5.71 —

— — — — — —

— — — — — —

a

Among patients with diverticulitis. Among patients who received endoscopy.

b

Clinical Gastroenterology and Hepatology Vol.

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Alexandersson et al Andrade et al Chabok et al Chan et al Choi et al Daniels et al Elmi et al Flor et al Grahnat et al Hjern et al Horesh et al Isacson et al Kim et al Lahat et al Lam et al Lau et al Lecleire et al Meireles et al Meyer et al Mortensen et al Ou et al Ramphal et al Sakhnini et al Sallinen et al Schmilovitz-Weiss et al Schout et al Suhardja et al Syed et al van de Wall et al Westwood et al Zaman et al

Direct colonic evaluation (patient, n)

Meyer et al

Study

Patient (n)

-,

No. -

2263 2264 2265 2266 2267 2268 2269 2270 2271 2272 2273 2274 2275 2276 2277 2278 2279 2280 2281 2282 2283 2284 2285 2286 2287 2288 2289 2290 2291 2292 2293 2294 2295 2296 2297 2298 2299 2300 2301 2302 2303 2304 2305 2306 2307 2308 2309 2310 2311 2312 2313 2314 2315 2316 2317 2318 2319 2320

2321 2322 2323 2324 2325 2326 2327 2328 2329 2330 2331 2332 2333 2334 2335 2336 2337 2338 2339 2340 2341 2342 2343 2344 2345 2346 2347 2348 2349 2350 2351 2352 2353 2354 2355 2356 2357 2358 2359 2360 2361 2362 2363 2364 2365 2366 2367 2368 2369 2370 2371 2372 2373 2374 2375 2376 2377 2378 -

Supplementary Table 9. Characteristics of Included Studies Regarding Prevalence of Adenoma Direct colonic evaluation (patient, n)

Direct colonic evaluationa (patient, %)

Endoscopy (patient, n)

Endoscopya (patient, %)

Adenoma (patient, n)

Adenomab (patient, %)

Alexandersson et al Andrade et al Chabok et al Chan et al Choi et al Daniels et al Elmi et al Flor et al Grahnat et al Hjern et al Horesh et al Isacson et al Kim et al Lahat et al Lam et al Lau et al Lecleire et al Meireles et al Meyer et al Mortensen et al Ou et al Ramphal et al Sakhnini et al Sallinen et al Schmilovitz-Weiss et al Schout et al Suhardja et al Syed et al van de Wall et al Westwood et al Zaman et al

282 252 108 55 149 401 402 46 890 50 425 155 177 86 288 1088 404 427 506 40,496 285 645 93 633 200 422 523 123 307 292 235

234 252 108 27 149 401 402 46 — 50 310 150 61 86 — 319 404 427 — 22,646 114 645 93 394 100 381 270 42 205 205 100

82.98 100.00 100.00 49.09 100.00 100.00 100.00 100.00 — 100.00 72.94 96.77 34.46 100.00 — 29.32 100.00 100.00 — 55.92 40.00 100.00 100.00 62.24 50.00 90.28 51.63 34.15 66.78 70.21 42.55

199 252 108 27 149 401 402 — — 50 310 — 61 86 — 319 404 427 — 22,646 113 645 93 394 100 378 270 42 205 175 100

70.57 100.00 100.00 49.09 100.00 100.00 100.00 — — 100.00 72.94 — 34.46 100.00 — 29.32 100.00 100.00 — 55.92 39.65 100.00 100.00 62.24 50.00 89.57 51.63 34.15 66.78 59.93 42.55

— 37 — — 47 76 55 6 — — — — 11 — 18 — 49 81 — — 23 — — 45 — 39 34 3 18 19 8

— 14.68 — — 31.54 18.95 13.68 — — — — — 18.03 — — — 12.13 18.97 — — 20.35 — — 11.42 — 10.32 12.59 7.14 8.78 10.86 8.00

Adenoma (n)

Adenomab (%)

13 — — — — 103 — — — — — — — — 18 — 50 — — — 23 — 10

6.53 — — — — 25.69 — — — — — — — — — — 12.38 — — — 20.35 — 10.75

.

. 41 — — — — — —

41.00 — — — — — —

a

Among patients with diverticulitis. Among patients who received endoscopy.

b

Colorectal Cancer in Patients With Acute Diverticulitis

Patient (n)

2018

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Study

9.e12

2379 2380 2381 2382 2383 2384 2385 2386 2387 2388 2389 2390 2391 2392 2393 2394 2395 2396 2397 2398 2399 2400 2401 2402 2403 2404 2405 2406 2407 2408 2409 2410 2411 2412 2413 2414 2415 2416 2417 2418 2419 2420 2421 2422 2423 2424 2425 2426 2427 2428 2429 2430 2431 2432 2433 2434 2435 2436

2437 2438 2439 2440 2441 2442 2443 2444 2445 2446 2447 2448 2449 2450 2451 2452 2453 2454 2455 2456 2457 2458 2459 2460 2461 2462 2463 2464 2465 2466 2467 2468 2469 2470 2471 2472 2473 2474 2475 2476 2477 2478 2479 2480 2481 2482 2483 2484 2485 2486 2487 2488 2489 2490 2491 2492 2493 2494 9.e13

Supplementary Table 10. Characteristics of Included Studies Regarding Prevalence of Hyperplastic Polyp Direct colonic evaluationa (patient, %)

Endoscopy (patient, n)

Endoscopya (patient, %)

Hyperplastic polyp (patient, n)

Hyperplastic polypb (patient, %)

Hyperplastic polyp (n)

Hyperplastic polypb (%)

282 252 108 55 149 401 402 46 890 50 425 155 177 86 288 1088 404 427 506 40,496 285 645 93 633 200

234 252 108 27 149 401 402 46 — 50 310 150 61 86 — 319 404 427 — 22,646 114 645 93 394 100

82.98 100.00 100.00 49.09 100.00 100.00 100.00 100.00 — 100.00 72.94 96.77 34.46 100.00 — 29.32 100.00 100.00 — 55.92 40.00 100.00 100.00 62.24 50.00

199 252 108 27 149 401 402 — — 50 310 — 61 86 — 319 404 427 — 22,646 113 645 93 394 100

70.57 100.00 100.00 49.09 100.00 100.00 100.00 — — 100.00 72.94 — 34.46 100.00 — 29.32 100.00 100.00 — 55.92 39.65 100.00 100.00 62.24 50.00

— 23 — — — — 21 2 — — — — 6 — — — 42 37 — — 11 — 0 49 —

— 9.13 — — — — 5.22 — — — — — 9.84 — — — 10.40 8.67 — — 9.73 — 0.00 12.44 —

19 — — — — 109 — — — — — — — — — — — — — — 11 — 0 — 6

9.55 — — — — 27.18 — — — — — — — — — — — — — — 9.73 — 0.00 — 6.00

422 523 123 307 292 235

381 270 42 205 205 100

90.28 51.63 34.15 66.78 70.21 42.55

378 270 42 205 175 100

89.57 51.63 34.15 66.78 59.93 42.55

— 25 9 15 20 4

— 9.26 21.43 7.32 11.43 4.00

— — — — — —

— — — — — —

a

Among patients with diverticulitis. Among patients who received endoscopy.

b

Clinical Gastroenterology and Hepatology Vol.

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Alexandersson et al Andrade et al Chabok et al Chan et al Choi et al Daniels et al Elmi et al Flor et al Grahnat et al Hjern et al Horesh et al Isacson et al Kim et al Lahat et al Lam et al Lau et al Lecleire et al Meireles et al Meyer et al Mortensen et al Ou et al Ramphal et al Sakhnini et al Sallinen et al Schmilovitz-Weiss et al Schout et al Suhardja et al Syed et al van de Wall et al Westwood et al Zaman et al

Direct colonic evaluation (patient, n)

Meyer et al

Study

Patient (n)

-,

No. -

2495 2496 2497 2498 2499 2500 2501 2502 2503 2504 2505 2506 2507 2508 2509 2510 2511 2512 2513 2514 2515 2516 2517 2518 2519 2520 2521 2522 2523 2524 2525 2526 2527 2528 2529 2530 2531 2532 2533 2534 2535 2536 2537 2538 2539 2540 2541 2542 2543 2544 2545 2546 2547 2548 2549 2550 2551 2552

-

2553 2554 2555 2556 2557 2558 2559 2560 2561 2562 2563 2564 2565 2566 2567 2568 2569 2570 2571 2572 2573 2574 2575 2576 2577 2578 2579 2580 2581 2582 2583 2584 2585 2586 2587 2588 2589 2590 2591 2592 2593 2594 2595 2596 2597 2598 2599 2600 2601 2602 2603 2604 2605 2606 2607 2608 2609 2610

2018

Colorectal Cancer in Patients With Acute Diverticulitis

9.e14

Supplementary Table 11. Leave-one-out Sensitivity Analysis for Estimation of Pooled Prevalence of Polyp Polyp (patient) Study omitted Alexandersson et al, 2014 Andrade et al, 2017 Chabok et al, 2013 Chan et al, 2017 Choi et al, 2014 Daniels et al, 2015 Elmi et al, 2013 Flor et al, 2015 Grahnat et al, 2016 Hjern et al, 2007 Horesh et al, 2016 Isacson et al, 2015 Kim et al, 2014 Lahat et al, 2007 Lam et al, 2010 Lau et al, 2011 Lecleire et al, 2014 Meireles et al, 2015 Meyer et al, 2015 Mortensen et al, 2017 Ou et al, 2015 Ramphal et al, 2016 Sakhnini et al, 2004 Sallinen et al, 2013 Schmilovitz-Weiss et al, 2012 Schout et al, 2012 Suhardja et al, 2017 Syed et al, 2016 van de Wall et al, 2012 Westwood et al, 2011 Zaman et al, 2017

Polyp (n)

Pooled prevalence (95% CI)

I2 (%)

Pooled prevalence (95% CI)

I2 (%)

0.2239 (0.1923–0.2592) 0.2286 (0.1972–0.2633) 0.2267 (0.1958–0.2609)

85.2 85.1 85.3

0.3022 (0.1772–0.4654)

97.3

0.2733 (0.1548–0.4357) 0.2943 (0.1726–0.4546)

97.5 97.5

0.2204 (0.1946–0.2486) 0.2284 (0.1965–0.2638)

76.1 84.7

0.2490 (0.1887–0.3209)

87.9

0.2323 (0.2015–0.2662)

83.5

0.2234 (0.1926–0.2575) 0.2339 (0.2037–0.2671)

85.2 83.8

0.3134 (0.1877–0.4742)

97.4

0.2245 (0.1925–0.2601) 0.2262 (0.1939–0.2621) 0.2233 (0.1914–0.2589)

85.3 85.3 85.0

0.2936 (0.1647–0.4670)

97.3

0.2231 0.2297 0.2335 0.2254 0.2211

(0.1922–0.2575) (0.1982–0.2646) (0.2030–0.2671) (0.1930–0.2613) (0.1910–0.2545)

85.1 83.6 84.0 85.3 84.4

0.2870 (0.1638–0.4527)

97.5

0.3109 (0.1855–0.4718)

97.4

0.2728 (0.1549–0.4344)

97.5

0.2268 0.2246 0.2289 0.2234 0.2310

(0.1948–0.2622) (0.1938–0.2588) (0.1973–0.2639) (0.1922–0.2582) (0.1999–0.2653)

85.3 85.3 84.9 85.1 84.7

0.2953 (0.1685–0.4642) 0.2886 (0.1677–0.4497)

97.4 97.5

0.2883 (0.1629–0.4574)

97.5

FLA 5.5.0 DTD
YJCGH55977_proof
17 October 2018
1:19 pm
ce CLR

2611 2612 2613 2614 2615 2616 2617 2618 2619 2620 2621 2622 2623 2624 2625 2626 2627 2628 2629 2630 2631 2632 2633 2634 2635 2636 2637 2638 2639 2640 2641 2642 2643 2644 2645 2646 2647 2648 2649 2650 2651 2652 2653 2654 2655 2656 2657 2658 2659 2660 2661 2662 2663 2664 2665 2666 2667 2668

9.e15

2669 2670 2671 2672 2673 2674 2675 2676 2677 2678 2679 2680 2681 2682 2683 2684 2685 2686 2687 2688 2689 2690 2691 2692 2693 2694 2695 2696 2697 2698 2699 2700 2701 2702 2703 2704 2705 2706 2707 2708 2709 2710 2711 2712 2713 2714 2715 2716 2717 2718 2719 2720 2721 2722 2723 2724 2725 2726

Meyer et al

Clinical Gastroenterology and Hepatology Vol.

-,

No.

-

Supplementary Table 12. Leave-one-out Sensitivity Analysis for Estimation of Pooled Prevalence of Advanced Adenoma Polyp (patient) Study omitted Alexandersson et al, 2014 Andrade et al, 2017 Chabok et al, 2013 Chan et al, 2017 Choi et al, 2014 Daniels et al, 2015 Elmi et al, 2013 Flor et al, 2015 Grahnat et al, 2016 Hjern et al, 2007 Horesh et al, 2016 Isacson et al, 2015 Kim et al, 2014 Lahat et al, 2007 Lam et al, 2010 Lau et al, 2011 Lecleire et al, 2014 Meireles et al, 2015 Meyer et al, 2015 Mortensen et al, 2017 Ou et al, 2015 Ramphal et al, 2016 Sakhnini et al, 2004 Sallinen et al, 2013 Schmilovitz-Weiss et al, 2012 Schout et al, 2012 Suhardja et al, 2017 Syed et al, 2016 van de Wall et al, 2012 Westwood et al, 2011 Zaman et al, 2017

Polyp (n)

Pooled prevalence (95% CI)

I2 (%)

Pooled prevalence (95% CI)

I2 (%)

0.2239 (0.1923–0.2592) 0.2286 (0.1972–0.2633) 0.2267 (0.1958–0.2609)

85.2 85.1 85.3

0.3022 (0.1772–0.4654)

97.3

0.2733 (0.1548–0.4357) 0.2943 (0.1726–0.4546)

97.5 97.5

0.2204 (0.1946–0.2486) 0.2284 (0.1965–0.2638)

76.1 84.7

0.2490 (0.1887–0.3209)

87.9

0.2323 (0.2015–0.2662)

83.5

0.2234 (0.1926–0.2575) 0.2339 (0.2037–0.2671)

85.2 83.8

0.3134 (0.1877–0.4742)

97.4

0.2245 (0.1925–0.2601) 0.2262 (0.1939–0.2621) 0.2233 (0.1914–0.2589)

85.3 85.3 85.0

0.2936 (0.1647–0.4670)

97.3

0.2231 0.2297 0.2335 0.2254 0.2211

(0.1922–0.2575) (0.1982–0.2646) (0.2030–0.2671) (0.1930–0.2613) (0.1910–0.2545)

85.1 83.6 84.0 85.3 84.4

0.2870 (0.1638–0.4527)

97.5

0.3109 (0.1855–0.4718)

97.4

0.2728 (0.1549–0.4344)

97.5

0.2268 0.2246 0.2289 0.2234 0.2310

(0.1948–0.2622) (0.1938–0.2588) (0.1973–0.2639) (0.1922–0.2582) (0.1999–0.2653)

85.3 85.3 84.9 85.1 84.7

0.2953 (0.1685–0.4642) 0.2886 (0.1677–0.4497)

97.4 97.5

0.2883 (0.1629–0.4574)

97.5

FLA 5.5.0 DTD
YJCGH55977_proof
17 October 2018
1:19 pm
ce CLR

2727 2728 2729 2730 2731 2732 2733 2734 2735 2736 2737 2738 2739 2740 2741 2742 2743 2744 2745 2746 2747 2748 2749 2750 2751 2752 2753 2754 2755 2756 2757 2758 2759 2760 2761 2762 2763 2764 2765 2766 2767 2768 2769 2770 2771 2772 2773 2774 2775 2776 2777 2778 2779 2780 2781 2782 2783 2784

-

2785 2786 2787 2788 2789 2790 2791 2792 2793 2794 2795 2796 2797 2798 2799 2800 2801 2802 2803 2804 2805 2806 2807 2808 2809 2810 2811 2812 2813 2814 2815 2816 2817 2818 2819 2820 2821 2822 2823 2824 2825 2826 2827 2828 2829 2830 2831 2832 2833 2834 2835 2836 2837 2838 2839 2840 2841 2842

2018

Colorectal Cancer in Patients With Acute Diverticulitis

9.e16

Supplementary Table 13. Leave-one-out Sensitivity Analysis for Estimation of Pooled Prevalence of Adenoma Adenoma (patient) Study omitted Alexandersson et al, 2014 Andrade et al, 2017 Chabok et al, 2013 Chan et al, 2017 Choi et al, 2014 Daniels et al, 2015 Elmi et al, 2013 Flor et al, 2015 Grahnat et al, 2016 Hjern et al, 2007 Horesh et al, 2016 Isacson et al, 2015 Kim et al, 2014 Lahat et al, 2007 Lam et al, 2010 Lau et al, 2011 Lecleire et al, 2014 Meireles et al, 2015 Meyer et al, 2015 Mortensen et al, 2017 Ou et al, 2015 Ramphal et al, 2016 Sakhnini et al, 2004 Sallinen et al, 2013 Schmilovitz-Weiss et al, 2012 Schout et al, 2012 Suhardja et al, 2017 Syed et al, 2016 van de Wall et al, 2012 Westwood et al, 2011 Zaman et al, 2017

Adenoma (n)

Pooled prevalence (95% CI)

I2 (%)

Pooled prevalence (95% CI)

I2 (%)

0.1415 (0.1151–0.1727)

81.8

0.2055 (0.127–0.3149)

92.1

0.1342 (0.1148–0.1562) 0.1383 (0.1127–0.1687) 0.1422 (0.1154–0.174)

67.3 80.3 81.6

0.1575 (0.0798–0.2871)

93.3

0.1402 (0.115–0.17)

81.7

0.1438 (0.1173–0.1751) 0.1383 (0.1126–0.1687)

81 80.1

0.1854 (0.1038–0.309)

92.3

0.1385 (0.1134–0.168)

81.1

0.1671 (0.09–0.2892)

94.4

0.1878 (0.1079–0.3065)

94

0.1446 (0.1182–0.1756)

80.6 0.1418 (0.0854–0.2262)

90.9

0.1459 0.1433 0.1446 0.1468 0.1446 0.146

79.8 81.4 81.3 80 81.1 80.8

(0.1199–0.1763) (0.1169–0.1744) (0.1194–0.1741) (0.1212–0.1767) (0.1187–0.1752) (0.1205–0.1758)

FLA 5.5.0 DTD
YJCGH55977_proof
17 October 2018
1:19 pm
ce CLR

2843 2844 2845 2846 2847 2848 2849 2850 2851 2852 2853 2854 2855 2856 2857 2858 2859 2860 2861 2862 2863 2864 2865 2866 2867 2868 2869 2870 2871 2872 2873 2874 2875 2876 2877 2878 2879 2880 2881 2882 2883 2884 2885 2886 2887 2888 2889 2890 2891 2892 2893 2894 2895 2896 2897 2898 2899 2900

9.e17 2901 2902 2903 2904 2905 2906 2907 2908 2909 2910 2911 2912 2913 2914 2915 2916 2917 2918 2919 2920 2921 2922 2923 2924 2925 2926 2927 2928 2929 2930 2931 2932 2933 2934 2935 2936 2937 2938 2939 2940 2941 2942 2943 2944 2945 2946 2947 2948 2949 2950 2951 2952 2953 2954 2955 2956 2957 2958 2959 2960 2961 2962 2963

Meyer et al

Clinical Gastroenterology and Hepatology Vol.

-,

No.

-

Supplementary Table 14. Leave-one-out Sensitivity Analysis for Estimation of Pooled Prevalence of Hyperplastic Polyp Hyperplastic polyp (patient) Study omitted Alexandersson et al, 2014 Andrade et al, 2017 Chabok et al, 2013 Chan et al, 2017 Choi et al, 2014 Daniels et al, 2015 Elmi et al, 2013 Flor et al, 2015 Grahnat et al, 2016 Hjern et al, 2007 Horesh et al, 2016 Isacson et al, 2015 Kim et al, 2014 Lahat et al, 2007 Lam et al, 2010 Lau et al, 2011 Lecleire et al, 2014 Meireles et al, 2015 Meyer et al, 2015 Mortensen et al, 2017 Ou et al, 2015 Ramphal et al, 2016 Sakhnini et al, 2004 Sallinen et al, 2013 Schmilovitz-Weiss et al, 2012 Schout et al, 2012 Suhardja et al, 2017 Syed et al, 2016 van de Wall et al, 2012 Westwood et al, 2011 Zaman et al, 2017

Hyperplastic polyp (n)

Pooled prevalence (95% CI)

I2 (%)

0.0923 (0.0742–0.1144)

62.0

0.0986 (0.0825–0.1174)

44.6

0.0920 (0.0747–0.1129)

62.0

0.0908 (0.0725–0.1132) 0.0929 (0.0743–0.1155)

61.5 61.5

0.0919 (0.0743–0.1132) 0.0940 (0.0781–0.1128) 0.0889 (0.0721–0.1091)

0.0922 0.0886 0.0942 0.0904 0.0953

(0.0740–0.1143) (0.0737–0.1062) (0.0764–0.1157) (0.0729–0.1116) (0.0785–0.1152)

Pooled prevalence (95% CI)

I2 (%)

0.0886 (0.0287–0.2425)

91.6

0.0787 (0.0484–0.1254)

43.9

62.1

0.0901 (0.0309–0.2349)

93

55.2 54.7

0.1179 (0.0514–0.2482)

93

0.1072 (0.0419–0.2477)

92.4

62.0 50.9 60.4 61.0 57.1

FLA 5.5.0 DTD
YJCGH55977_proof
17 October 2018
1:19 pm
ce CLR

2964 2965 2966 2967 2968 2969 2970 2971 2972 2973 2974 2975 2976 2977 2978 2979 2980 2981 2982 2983 2984 2985 2986 2987 2988 2989 2990 2991 2992 2993 2994 2995 2996 2997 2998 2999 3000 3001 3002 3003 3004 3005 3006 3007 3008 3009 3010 3011 3012 3013 3014 3015 3016 3017 3018 3019 3020 3021 3022 3023 3024 3025 3026