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Article

Recurrence of Uncomplicated Diverticulitis: A Meta-Analysis

by
Guhyun Kang
1,†,
Soomin Son
2,†,
Young-Min Shin
3 and
Jung-Soo Pyo
4,*
1
Department of Pathology, Daehang Hospital, Seoul 06699, Korea
2
Division of Molecular Life and Chemical Sciences, College of Natural Sciences, Ewha Woman’s University, Seoul 03760, Korea
3
Eulji University School of Medicine, Daejeon 34824, Korea
4
Department of Pathology, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu 11759, Korea
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Medicina 2022, 58(6), 758; https://doi.org/10.3390/medicina58060758
Submission received: 7 May 2022 / Revised: 27 May 2022 / Accepted: 29 May 2022 / Published: 2 June 2022
(This article belongs to the Section Surgery)
Browse Figures
Versions Notes

Abstract

:
Background and objective: This study aimed to investigate the estimated rate and risk of recurrence of uncomplicated diverticulitis (UCD) after the first episode through a meta-analysis. Methods: Eligible studies were searched and reviewed; 27 studies were included in this study. Subgroup analyses were performed, based on lesion location, medical treatment, follow-up period, and study location. Results: The estimated recurrence rate of UCD was 0.129 (95% confidence interval [CI] 0.102–0.162). The recurrence rates of the right-and left-sided colon were 0.092 (95% CI 27.063–0.133) and 0.153 (95% CI 0.104–0.218), respectively. The recurrence rate according to follow-up period was highest in the subgroup 1–2 years, compared with that of other subgroups. The recurrence rate of the Asian subgroup was significantly lower than that of the non-Asian subgroup (0.092, 95% CI 0.064–0.132 vs. 0.147, 95% CI 0.110–0.192; p = 0.043 in the meta-regression test). There were significant correlations between UCD recurrence and older age and higher body temperature. However, UCD recurrence was not significantly correlated with medications, such as antibiotics or anti-inflammatory drugs. Conclusions: In this study, detailed information on estimated recurrence rates of UCD was obtained. In addition, older age and higher body temperature may be risk factors for UCD recurrence after the first episode.

1. Introduction

Acute diverticulitis develops in 4–25% of patients with diverticulosis [1,2,3]. Uncomplicated diverticulitis (UCD) accounts for 75% of all acute diverticulitis cases [3,4]. Recurrence occurs in approximately one-third of the patients with diverticulitis [2]. Treatment guidelines regarding antibiotics can differ between countries [5,6,7]. Traditionally, treatment of UCD includes bowel rest, intravenous fluids, and antibiotics. However, recent randomized controlled trials (RCTs) have reported the comparison between antibiotics and non-antibiotics therapies in acute diverticulitis [8,9,10]. Avoiding antibiotics as a UCD treatment has been recommended in guidelines based on the results of previous RCTs and other studies [8,11,12,13,14]. However, antibiotics are commonly used in many institutions [15,16]. Estimates from large populations, such as recurrence rates, can be useful for the treatment of UCD in clinical practice. However, conclusive information cannot be obtained from individual studies. Meta-analyses can usefully integrate this information. Although previous meta-analyses have shown odds ratios of recurrence between antibiotics and non-antibiotics [1,17,18], estimated recurrence rates could not be obtained.
The risk of UCD recurrence after treatment remains unclear. The incidence of acute diverticulitis differs between locations and patient age groups [19,20,21]. In addition, recurrence rates may differ according to the patient group. We investigated the recurrence rates of UCD in eligible studies and analyzed the cumulative estimates through a meta-analysis. In the present study, recurrence rates, but not the odds ratio, were estimated as real values. Subgroup analyses were performed for the characteristics of the patients and studies, including lesion location, medication, follow-up period, and study location. In addition, risk of recurrence was evaluated according to various factors.

2. Materials and Methods

2.1. Published Studies Search and Selection Criteria

The search for the meta-analysis was performed in the PubMed and the MEDLINE databases through 15 March 2022. The keywords were “uncomplicated diverticulitis” and “recurrence or recur”. Articles with information of the recurrence in UCD were included in the present study. Case reports or non-original articles were excluded. In addition, the articles written in English were included. Detailed characteristics of the 27 eligible studies are shown in Figure 1 and Table 1.

2.2. Data Extraction

Two authors independently extracted data from eligible studies. The following data were extracted from all the eligible studies: the family name of the first author, year of publication, study location, number of patients analyzed, study type, lesion locations, medical treatment, and follow-up period [8,9,10,13,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44]. This study was performed by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

2.3. Statistical Analyses

All data were analyzed using the Comprehensive Meta-Analysis software package (Biostat, Englewood, NJ, USA). The recurrence rates of UCD after the first episode were investigated. Subgroup analyses were performed based on the location of the UCD, treatment, periods of follow-up, study location, and study type. Analysis for heterogeneity between the studies was conducted and evaluated using the Q and I2 statistics and expressed as p-values. In addition, the statistical significance of the difference between subgroups was evaluated through the meta-regression test. In the assessment of estimated values, because the eligible studies were evaluated in different populations with variable treatments, the application of a random-effect model rather than a fixed-effect model was more suitable. Publication bias was evaluated using Begg’s funnel plot and Egger’s test. If significant publication bias was found, the degree of publication bias was confirmed through fail-safe N and trim-fill tests. The statistical difference between the subgroups was evaluated through a meta-regression test. The results were considered to be statistically significant at p < 0.05.

3. Results

3.1. Selection and Characteristics of the Studies

A search in the database was performed, and 267 articles were initially found. Through the review of the title and abstract, 52 full-text articles were assessed for eligibility. Finally, 27 articles were included in this meta-analysis. In detail, the causes for the exclusion of the searched articles are shown in Figure 1. Of these, 142 reports were excluded because they were non-original articles. Next, 97 articles were excluded because of insufficient or no information. Another study was excluded due to an article for another disease (n = 1). This estimate was obtained from 6731 patients in 27 eligible studies.

3.2. The Recurrence Rates of Uncomplicated Diverticulitis

The estimated recurrence rate of UCD was 0.129 (95% CI 0.102–0.162; Figure 2). Subgroup analyses were performed based on the location of lesions, medical treatment, periods of follow-up, study location, and study type. The recurrence rates in right-and left-sided colons were 0.092 (95% CI 0.063–0.133) and 0.153 (95% CI 0.104–0.218), respectively (Table 2). However, there was no significant difference in the recurrence rates between right- and left-sided colons in the meta-regression test (p = 0.062). The recurrence rates of patients with antibiotics or conservative treatments were 0.130 (95% CI 0.096–0.175) and 0.154 (95% CI 0.116–0.202), respectively. The recurrence rate was 0.088 (95% CI 0.045–0.163) in the subgroup with an anti-inflammatory drug. For subgroup analysis based on follow-up periods, subgroups were divided into three categories, such as < 1 year, 1–2 years, and > 2 years. The recurrence rate was higher in follow-up 1–2 years than in other periods. However, there was no significant difference between follow-up periods in the meta-regression test. In subgroup analysis based on study location, the recurrence rates were 0.147 (95% CI 0.110–0.192) and 0.092 (95% CI 0.064–0.132) in Europe and Asia, respectively. There was a statistical significance between the recurrence rates of Europe and Asia subgroups in the meta-regression test (p = 0.043).

3.3. Comparison of Recurrence of Uncomplicated Diverticulitis According to the Patients’ Characteristics

Next, the risk factors of UCD recurrence were evaluated through comparisons of the odds ratio. Evaluating risk factors included age, sex, white blood cell (WBC) count, C-reactive protein (CRP), body mass index, smoking history, body temperature, multiplicity, and types of medication. Recurrence occurred more frequently in older ages than in younger ages (odds ratio 1.841, 95% CI 1.189–2.851; Table 3). In addition, patients with a high body temperature showed a higher recurrence rate than those with a low body temperature (odds ratio 11.233, 95% CI 1.290–97.824). However, there were no impacts of other risk factors on the recurrence of UCD. Interestingly, patients taking anti-inflammatory drugs showed less frequent recurrence than those not taking anti-inflammatory drugs.

4. Discussion

Two RCTs, the AVOD trial and the DIABOLO trial, reported that antibiotics had no significant effect on preventing UCD complications or recurrence [9,10]. However, these RCTs have limitations in interpreting various factors associated with recurrence. In addition, previous meta-analyses did not provide real estimates of recurrence of UCD after treatment. To the best of our knowledge, this is the first meta-analysis to report estimated recurrence rates of UCD after conservative versus medical treatment.
The range of follow-up periods was broad, from four weeks to 11 years in eligible studies. Studies included 22–583 patients. Information from individual studies may vary depending on population or research settings. In Kim’s report, recurrence rates were 9.8% and 7.8% in subgroups with and without antibiotics, respectively [31]. In contrast, Isacson et al. reported a recurrence rate of 31.3% [30]. In theory, a longer follow-up period may be associated with a higher recurrence rate. It can be difficult to draw conclusions from individual studies. This meta-analysis may be useful for obtaining integrated conclusions. In the present study, the estimated recurrence rate was 0.129 (95% CI 0.102–0.162). The estimated recurrence rate ranged from 0.7% to 38.2%. Recurrence can be affected by various factors, such as treatment, location, and follow-up period. Interestingly, the European subgroup had higher recurrence rates than the Asian subgroup (0.147 vs. 0.092; p = 0.043 in the meta-regression test). However, there were no significant differences in recurrence rates according to lesion location, medical treatment, or follow-up period.
In the present study, we compared the risk of UCD recurrence according to patient characteristics. Older patients and those with a high body temperature had a significantly higher risk of UCD recurrence than younger patients and those with a low body temperature. In the present study, patients taking anti-inflammatory drugs had an odds ratio of less than 1.000, compared with those not taking anti-inflammatory drugs. However, there was no statistically significant difference between patients treated with and without anti-inflammatory drugs. Other characteristics, such as sex, WBC count, CRP level, smoking history, and multiplicity, had odds ratios higher than 1.000. However, statistical significance was not observed for these factors. In daily practice, evaluation factors obtained from peripheral blood samples can be useful due to the ease of assessment and common laboratory findings. The odds ratio between patients with higher and lower CRP levels was 2.155 (95% CI 0.608–7.643). Although statistical significance was identified in two of the three eligible studies [23,32], the estimated overall odds ratio was not significant. The odds ratios of each study were 6.58 (95% CI 1.05–41.07) and 1.00 (95% CI 1.00–1.01). However, because the CRP levels can be affected by patient conditions and disease progression, more cumulative studies are needed.
Several meta-analyses have reported on UCD recurrence. When recurrence was compared between subgroups with and without antibiotics through meta-analysis [1,17,18], the studies reported no significant difference in the UCD recurrence rates between subgroups. However, the estimated recurrence rate of UCD after antibiotic or conservative treatment could not be obtained from previous meta-analyses. Unlike previous studies, the present study investigated and evaluated estimated recurrence rates. In our results, the overall estimated recurrence rate of UCDs was 0.129 (95% CI 0.102–0.162). In addition, we performed a detailed subgroup analysis based on lesion location, medical treatment, follow-up period, study location, and study type. The odds ratios of the recurrence rates of the medication and non-medication subgroups were similar to those of previous meta-analyses [1,17,18].
This study had several limitations. First, our meta-analysis included various types of studies, such as an RCT, prospective studies, and retrospective studies. Recurrence rates were 0.162 (95% CI 0.094–0.265), 0.110 (95% CI 0.062–0.191), and 0.123 (95% CI 0.093–0.161) in the RCT, prospective study, and retrospective study subgroups, respectively. However, there was no significant difference in recurrence rates between study types in the meta-regression test. A detailed analysis based on various conditions in each study type could not be performed due to insufficient information. Second, eligible studies were mainly conducted in Europe and Asia. Detailed impacts of study location and race on recurrence rates of UCD could not be determined.

5. Conclusions

In conclusion, the UCD recurrence rate was estimated to be 12.9%. Recurrence rates were significantly lower in the Asian subgroup, younger patients, and the high body temperature subgroup than in the European subgroup, older patients, and the low body temperature subgroup. In addition, antibiotics treatment has no significant effect on the reduction of recurrence rates in UCD. In this study, we illustrate the recurrence rate that can be expected by each patient’s group.

Author Contributions

Conceptualization, S.S. and J.-S.P.; methodology, G.K. and J.-S.P.; software, G.K. and J.-S.P.; validation, G.K. and S.S.; formal analysis, G.K. and J.-S.P.; investigation, G.K. and S.S.; resources, J.-S.P.; data curation, J.-S.P.; writing—original draft preparation, S.S. and J.-S.P.; writing—review and editing, G.K. and Y.-M.S.; supervision, J.-S.P.; project administration, J.-S.P. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Conflicts of Interest

The authors declare that they have no potential conflict of interest.

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Medicina 58 00758 g001 550
Figure 1. Flow chart of study search and selection methods.
Figure 1. Flow chart of study search and selection methods.
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Medicina 58 00758 g002 550
Figure 2. Forest plot for the recurrence rate of uncomplicated diverticulitis.
Figure 2. Forest plot for the recurrence rate of uncomplicated diverticulitis.
Medicina 58 00758 g002
Table
Table 1. Main characteristics of eligible studies.
Table 1. Main characteristics of eligible studies.
First AuthorLocationStudy TypeFollow-Up
Period		LesionIncluded Medical TreatmentNumber of
Patients
Azhar 2022SwedenRetrospective6 mo.OverallAntibiotics583
Brochmann 2016NorwayRetrospective12 mo.Left-sideAntibiotics220
Buchs 2013SwitzerlandProspective24 mo.Left-sideND280
Chabok 2012SwedenRCT (AVOD)12 mo.Left-sideAntibiotics582
Courtot 2019FranceRetrospective33.2 mo.Right-sideAntibiotics59
Daniels 2017NetherlandsRCT (DIABOLO)6 mo.Left-sideAntibiotics528
Demircioglu 2020TurkeyRetrospective38 mo.OverallAntibiotics134
Destek 2019TurkeyRetrospective2 yearsRight-sideAntibiotics22
Eglinton 2010New ZealandRetrospective101 mo.Left-sideNo320
Gatta 2012ItalyProspective60 mo.OverallAnti-inflammatory125
Ha 2017KoreaRetrospective61 mo.Right-sideAntibiotics152
Isacson 2015SwedenProspective3 mo.Left-sideNo150
Isacson 2019SwedenRCT (AVOD)11 yearsLeft-sideAntibiotics456
Kim 2019KoreaProspective4-6 weeksRight-sideAntibiotics125
Kruis 2017VariousRCT48 weeksLeft-sideAnti-inflammatory211
Matsushima 2010JapanRetrospectiveNDOverallAntibiotics123
Meyer 2019SwitzerlandRetrospective10 yearsLeft-sideAntibiotics301
Parente 2013ItalyRCT24 mo.Left-sideAnti-inflammatory92
Park 2010KoreaRetrospective38 mo.Right-sideAntibiotics276
Park 2011KoreaRetrospective46 mo.Right-sideAntibiotics102
Park 2014KoreaRetrospective59 mo.Right-sideAntibiotics469
Park 2019KoreaRCTNDRight-sideAntibiotics176
Scarpa 2015SwitzerlandProspective12 mo.OverallAntibiotics256
Stallinger 2014ItalyRetrospective3 mo.OverallAnti-inflammatory311
Tursi 2013ItalyRetrospective24 mo.OverallAntibiotics and
Anti-inflammatory		114
van Dijk 2018NetherlandsRCT (DIABOLO)24 mo.Left-sideAntibiotics468
Yang 2006TaiwanRetrospective37.5 mo.Right-sideAntibiotics96
RCT, randomized clinical trial; mo., months; ND, no description.
Table
Table 2. The estimated recurrence rate of uncomplicated diverticulitis.
Table 2. The estimated recurrence rate of uncomplicated diverticulitis.
Number of
Subsets		Fixed Effect
[95% CI]		Heterogeneity Test
(p-Value)		Random Effect
[95% CI]		Egger’s
Test
(p-Value)		Meta-
Regression Test
(p-Value)
Overall270.190 [0.179, 0.200]<0.0010.129 [0.102, 0.162]<0.001
 Right colon90.120 [0.103, 0.140]<0.0010.092 [0.063, 0.133]0.0190.062
 Left colon110.217 [0.202, 0.232]<0.0010.153 [0.104, 0.218]0.008
 Antibiotics200.196 [0.183, 0.210]<0.0010.130 [0.096, 0.175]0.0020.741
 Anti-inflammatory50.127 [0.101, 0.158]<0.0010.088 [0.045, 0.163]0.122
 Non-antibiotics/
anti-inflammatory		100.180 [0.160, 0.202]<0.0010.154 [0.116, 0.202]0.089
 Follow-up < 1 year90.157 [0.143, 0.172]<0.0010.102 [0.066, 0.156]0.0100.437
 Follow-up 1–2 years50.207 [0.180, 0.238]0.0390.198 [0.152, 0.252]0.512
 Follow-up > 2 years120.220 [0.203, 0.238]<0.0010.128 [0.086, 0.186]0.001
 Europe180.207 [0.195, 0.220]<0.0010.147 [0.110, 0.192]0.0030.043 *
 Asia80.120 [0.103, 0.139]<0.0010.092 [0.064, 0.132]0.002
 Randomized clinical trial70.224 [0.206, 0.244]<0.0010.162 [0.094, 0.265]0.0800.297
 Prospective50.166 [0.141, 0.193]<0.0010.110 [0.061, 0.191]0.012
 Retrospective150.171 [0.158, 0.186]<0.0010.123 [0.093, 0.161]0.001
CI, Confidence interval; * Comparison between the Asian and the non-Asian studies.
Table
Table 3. Comparison of odds ratio in the recurrence of diverticulitis according to the patients’ characteristics.
Table 3. Comparison of odds ratio in the recurrence of diverticulitis according to the patients’ characteristics.
Number of
Subsets		Fixed Effect
[95% CI]		Heterogeneity Test
(p-Value)		Random Effect
[95% CI]		Egger’s
Test
(p-Value)
Age (Old vs. Young)31.841 [1.189, 2.851]0.6981.841 [1.189, 2.851]0.417
Sex (Male vs. Female)71.157 [0.925, 1.447]0.7611.157 [0.925, 1.447]0.571
WBC count (High vs. Low)21.010 [0.961, 1.061]0.9071.010 [0.961, 1.061]-
CRP (High vs. Low)32.346 [1.161, 4.741]0.0842.155 [0.608, 7.643]0.868
Body mass index (High vs. Low)40.974 [0.916, 1.035]0.2731.016 [0.796, 1.296]0.731
Smoking history (Yes vs. No)21.487 [0.887, 2.492]0.9131.487 [0.887, 2.492]-
Body temperature * (High vs. Low)111.233 [1.290, 97.824]1.00011.233 [1.290, 97.824]-
Multiplicity (Multiple vs. Single)32.152 [1.355, 3.420]0.1461.721 [0.720, 4.115]0.513
Medication (Yes vs. No)130.950 [0.787, 1.147]0.7970.950 [0.787, 1.147]0.931
 Antibiotics81.014 [0.828, 1.241]0.8481.014 [0.828, 1.241]0.063
 Anti-inflammatory drug50.639 [0.387, 1.056]0.7950.639 [0.387, 1.056]0.850
CI, Confidence interval; WBC, White blood cell; CRP, C-reactive protein. *, measuring during admission.
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Kang, G.; Son, S.; Shin, Y.-M.; Pyo, J.-S. Recurrence of Uncomplicated Diverticulitis: A Meta-Analysis. Medicina 2022, 58, 758. https://doi.org/10.3390/medicina58060758

AMA Style

Kang G, Son S, Shin Y-M, Pyo J-S. Recurrence of Uncomplicated Diverticulitis: A Meta-Analysis. Medicina. 2022; 58(6):758. https://doi.org/10.3390/medicina58060758

Chicago/Turabian Style

Kang, Guhyun, Soomin Son, Young-Min Shin, and Jung-Soo Pyo. 2022. "Recurrence of Uncomplicated Diverticulitis: A Meta-Analysis" Medicina 58, no. 6: 758. https://doi.org/10.3390/medicina58060758

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