Comparative outcomes of acute colonic diverticulitis in immunocompromised versus immunocompetent patients: a systematic review and meta-analysis

Jae Gon Lee; Yong Eun Park; Ji Young Chang; Hyun Joo Song; Duk Hwan Kim; Young Joo Yang; Byung Chang Kim; Shin Hee Lee; Myung-Won You; Seong-Eun Kim

doi:10.5217/ir.2023.00005

Articles

Page Path: HOME > Intest Res > Volume 21(4); 2023 > Article

Original Article Infection Comparative outcomes of acute colonic diverticulitis in immunocompromised versus immunocompetent patients: a systematic review and meta-analysis: Jae Gon Lee¹, Yong Eun Park², Ji Young Chang³, Hyun Joo Song⁴, Duk Hwan Kim⁵, Young Joo Yang⁶, Byung Chang Kim⁷, Shin Hee Lee⁸, Myung-Won You⁹, Seong-Eun Kim^10,; Intestinal Research 2023;21(4):481-492.
DOI: https://doi.org/10.5217/ir.2023.00005
Published online: May 31, 2023

¹Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea

²Division of Gastroenterology, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea

³Department of Health Promotion Medicine, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul, Korea

⁴Division of Gastroenterology, Department of Internal Medicine, Jeju National University Hospital, Jeju National University College of Medicine, Jeju, Korea

⁵Digestive Disease Center, CHA Bundang Medica Center, CHA University, Seongnam, Korea

⁶Division of Gastroenterology, Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea

⁷Center for Colorectal Cancer, National Cancer Center, Goyang, Korea

⁸Division of Gastroenterology, Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Korea

⁹Department of Radiology, Kyung Hee University Hospital, College of Medicine, Kyung Hee University, Seoul, Korea

¹⁰Division of Gastroenterology, Department of Internal Medicine, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, Korea

Correspondence to Seong-Eun Kim, Department of Internal Medicine, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Korea. Tel: +82-2-2650-5272, Fax: +82-2-2650-5936, E-mail: kimse@ewha.ac.kr

• Received: January 9, 2023 • Revised: February 22, 2023 • Accepted: March 31, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

prev next

2,766 Views
342 Download
1 Web of Science
1 Crossref
1 Scopus

Full Article

Download PDF

Abstract
INTRODUCTION
METHODS
RESULTS
DISCUSSION
NOTES
Supplementary Material
REFERENCES

See letter "Not all acute colonic diverticulitis follows the same course: a potential risk for immunocompromised individuals" in Volume 21 on page 415.

Abstract

Background/Aims
Immunocompromised patients with acute colonic diverticulitis are at high risk for complications and failure of non-surgical treatment. However, evidence on the comparative outcomes of immunocompromised and immunocompetent patients with diverticulitis is lacking. This systematic review and meta-analysis investigated the outcomes of medical treatment in immunocompromised and immunocompetent patients with diverticulitis.
Methods
A comprehensive literature search was conducted in PubMed, Embase, and the Cochrane Library. Studies comparing the clinical outcomes of immunocompromised and immunocompetent patients with diverticulitis were included.
Results
A total of 10 studies with 1,946,461 subjects were included in the quantitative synthesis. The risk of emergency surgery and postoperative mortality after emergency surgery was significantly higher in immunocompromised patients than in immunocompetent patients with diverticulitis (risk ratio [RR], 1.76; 95% confidence interval [CI], 1.31–2.38 and RR, 3.05; 95% CI, 1.70–5.45, respectively). Overall risk of complications associated with diverticulitis was non-significantly higher in immunocompromised than in immunocompetent patients (RR, 1.24; 95% CI, 0.95–1.63). Overall mortality irrespective of surgery was significantly higher in immunocompromised than in immunocompetent patients with diverticulitis (RR, 3.65; 95% CI, 1.73–7.69). By contrast, postoperative mortality after elective surgery was not significantly different between immunocompromised and immunocompetent patients with diverticulitis. In subgroup analysis, the risk of emergency surgery and recurrence was significantly higher in immunocompromised patients with complicated diverticulitis, whereas no significant difference was shown in mild disease.
Conclusions
Immunocompromised patients with diverticulitis should be given the best medical treatment with multidisciplinary approach because they had increased risks of surgery, postoperative morbidity, and mortality than immunocompetent patients.
Keywords: Colonic diverticulitis; Immunocompromised host; Treatment outcome

INTRODUCTION

Colonic diverticulitis, one of the most common gastrointestinal diseases, is frequently encountered in clinical practice [1]. The incidence of colonic diverticulitis has steadily increased over the past decades, particularly in younger patients [2,3]. Approximately 12% of acute diverticulitis cases manifest as a complicated disease with an abscess, peritonitis, stricture, or fistula [1]. Patients with abdominal sepsis who are hemodynamically unstable require surgical intervention and are at significant risk of mortality [2,4]. Approximately 20% of patients with acute colonic diverticulitis experience at least one recurrence [1]. Several studies have suggested immunosuppression as a risk factor for diverticulitis. Corticosteroid use is associated with an increased risk of complicated diverticulitis [5,6]. Patients with diverticulitis who are immunocompromised may present with milder symptoms and signs than immunocompetent patients but are more likely to present with severe or complicated disease [7]. In addition, immunocompromised patients with diverticulitis are at high risk for failure of non-surgical treatment [7-9]. Therefore, some guidelines recommend antibiotic treatment and early surgical consultation for immunocompromised patients with diverticulitis [10-12].

However, the natural history and clinical outcomes of diverticulitis in immunocompromised patients have yet to be fully elucidated. Most studies of diverticulitis in immunocompromised patients were small and observational, focusing on postoperative outcomes and used heterogenous definitions of immunosuppression. Although a recent systematic review and meta-analysis showed a greater risk of postoperative mortality and morbidity in immunocompromised patients with diverticulitis who underwent operative management [13], evidence on the comparative outcomes of medical treatment in patients with diverticulitis who are immunocompromised is lacking. Therefore, we conducted this systematic review and meta-analysis to compare the clinical outcomes of immunocompromised and immunocompetent patients with diverticulitis.

METHODS

1. Search Strategy

A comprehensive literature search was conducted in PubMed, Embase, and the Cochrane Library from 2000 to August 2022. The search terms included “immunocompromised,” “immunosuppressed,” “immunodeficient,” “colonic,” and “diverticulitis.” Detailed search strategies are presented in Supplementary Material. A manual search of the reference lists of identified studies was conducted to include all relevant articles.

2. Inclusion and Exclusion Criteria

All studies comparing the clinical outcomes of acute colonic diverticulitis between immunocompetent and immunocompromised patients were considered eligible. The inclusion criteria were based on the PICO framework: (1) population, patients with acute diverticulitis; (2) intervention, immunocompromised condition or immunosuppressive treatment; (3) comparator, immunocompetent status; and (4) outcome, need for surgery, complications, mortality, length of hospital stay, and recurrence. The exclusion criteria were as follows: (1) studies that did not include immunocompetent patients as a control; (2) studies that included only patients with surgically diagnosed diverticulitis or in which the diagnostic criteria were vague; (3) studies in which the definitions of immunocompetent and immunocompromised patients were ambiguous; (4) non-original articles including reviews, editorials, opinions, letters, case report, and case series; (5) abstract-only publications; (6) non-human studies; and (7) non-English publications.

3. Study Selection

Two investigators (J.G.L. and S.E.K.) independently screened the literature and selected studies. First, all duplicate articles from multiple databases were removed. Next, irrelevant articles were excluded by inspecting the titles and abstracts. The full texts of the remaining articles were reviewed for eligibility. Any disagreements were resolved by discussion. If consensus could not be reached, a third party (H.J.S.) determined study eligibility. Study selection was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement [14].

4. Data Extraction and Outcome Assessment

Using a standardized collection sheet, data were extracted from the included articles. The characteristics of the studies including the first author, year of publication, study design, study period, number of patients, and study endpoints were examined.

The primary endpoint was the comparison of clinical outcomes including need for surgical intervention (emergency or elective), complications, mortality, length of hospital stay, and recurrence between immunocompromised and immunocompetent patients with acute colonic diverticulitis.

Because this systematic review and meta-analysis did not include individual patients or patient data, ethical approval was not required.

5. Study Quality Assessment

Risk of bias assessment was performed independently by 2 investigators (J.G.L. and S.K.) using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS) version 2.0. RoBANS version 2.0 rates the risk of bias as high, low, or unclear in domains of participant comparability, selection of participants, confounding variables, measurement of exposure, blinding of outcome assessments, outcome evaluation, incomplete outcome data, and elective reporting [15]. Disagreements were discussed among the investigators until consensus was reached.

6. Statistical Analysis

A standard pairwise meta-analysis was conducted to compare clinical outcomes between immunocompromised and immunocompetent patients with acute colonic diverticulitis. Assessment of heterogeneity was performed using Cochrane’s Q test and inconsistency (I²) statistics. We considered I² > 50% or P < 0.1 to represent significant heterogeneity [16]. In the meta-analysis, a fixed-effect model was used if there was no considerable heterogeneity, and a random-effect model was used if there was considerable heterogeneity among studies. Pooled effect estimates were measured by calculating the risk ratios (RRs) for categorical variables and mean differences for continuous variables with 95% confidence intervals (CIs). Publication bias was not evaluated if the number of included studies was < 10 [17]. Statistical analyses were performed with Review Manager version 5.4 (The Cochrane Collaboration, 2020).

RESULTS

1. Study Selection

A total of 391 potentially relevant articles were identified through a comprehensive literature search. Three other articles were identified by manual searching. In total, 80 duplicate articles were removed and 278 articles were excluded based on the titles and abstracts. Subsequently, 36 full text articles were reviewed for eligibility. Twenty-six articles were excluded because they were abstracts without full text (n = 7), had outdated or inadequate diagnostic definitions (n = 2), were out of scope (n = 1), were review articles (n = 4), were not on PICO (n = 7), were duplicate publications (n = 4), or were in another language (n = 1). Finally, 10 studies were included in the quantitative synthesis. PRISMA flowchart is shown in Fig. 1.

2. Study Characteristics

Table 1 lists the characteristics of the 10 included studies [7,8,18-25]. Totals of 5,339 immunocompromised patients and 1,941,122 immunocompetent patients with acute diverticulitis requiring hospitalization were analyzed. The study period was 1988 to 2021. All included studies were observational studies. Seven of the 10 studies included patients with sigmoid or left colonic diverticulitis [7,8,18-21,24]. One study included all patients with left or right colonic diverticulitis, but most had sigmoid diverticulitis [22]. The remaining 2 studies did not clarify the location of diverticulitis, but it is presumed that most patients had left colonic diverticulitis considering the contents of their analysis [23,25].

The definitions of immunocompromised patients were heterogenous, including patients on immunosuppressive agents, chronic corticosteroid treatment, solid organ transplant, nongastrointestinal active malignancy, chemotherapy, collagen vascular disorders, end-stage renal disease, and congenital or acquired immunodeficiency.

3. Risk of Bias

Supplementary Fig. 1 shows the risk of bias assessment. Because all included studies were non-randomized observational studies, we used RoBANS version 2.0 tool to assess the risk of bias. Many studies were rated as unclear in the domains of confounding variables and selection of participants. In the domain of confounding variables, one study was rated as high risk because most immunocompromised patients were likely to have chronic medical illnesses of moderate or greater severity, an unavoidable limitation without statistical adjustment because these can act as confounding variables [8]. In the domain of selection of participants, one study was rated as high risk because the control group might have included patients who were not completely immunocompetent [22].

4. Need for Surgical Intervention

Five of the included studies reported rates of surgical intervention for acute diverticulitis [7,8,19,22,25]. Fig. 2 presents the forest plot of surgery rates. The overall risk of surgical intervention, emergency or elective, was not significantly different between immunocompromised and immunocompetent patients with acute colonic diverticulitis (RR, 1.26; 95% CI, 0.81–1.96). However, the rates of emergency surgery in immunocompromised and immunocompetent patients were 34.3% and 22.4%, respectively, showing a significantly higher risk in the immunocompromised patients (RR, 1.76; 95% CI, 1.31–2.38) in the meta-analysis (Z = 3.71, P = 0.0002, I² = 37%).

5. Complications

Four studies reported complications associated with acute diverticulitis [7,8,22,25]. Complications included abscess, perforation, obstruction, or fistula. The overall risk of complications associated with diverticulitis was non-significantly higher in immunocompromised than in immunocompetent patients (RR, 1.24; 95% CI, 0.95–1.63) (Fig. 3).

6. Mortality

Nine of the included studies reported mortality rates [7,8,18-24]. The overall mortality after acute colonic diverticulitis irrespective of surgical intervention was 4.7% in immunocompromised patients and 1.5% in immunocompetent patients. Meta-analysis revealed that the immunocompromised patients had a significantly higher risk of overall mortality (RR, 3.65; 95% CI, 1.73–7.69) (Z = 3.40, P = 0.0007, I² = 94%). Likewise, in patients who underwent emergency surgery, the risk of death was significantly higher in those with immunosuppression than in those without (RR, 3.05; 95% CI, 1.70–5.45) in the meta-analysis (Z = 3.75, P = 0.0002, I² = 87%), showing mortality rates of 13.1% and 4.9%, respectively. By contrast, among those who underwent elective surgery, the risk of death was not significantly different between immunocompromised and immunocompetent patients, although the results were significantly heterogeneous (RR, 2.02; 95% CI, 0.03–118.95) in the meta-analysis (Fig. 4).

7. Length of Hospital Stay

Six of the included studies reported the length of hospital stay [8,18,20-22]. Fig. 5 shows the forest plot for length of hospital stay. Immunocompromised patients with diverticulitis had a longer hospital stay than immunocompetent patients (mean difference, 6.12; 95% CI, 2.04–10.20).

8. Recurrence

Three studies reported recurrence rates after the first episode of diverticulitis [7,22,25]. The duration of follow-up was a median of 33 to 44 months in 2 studies [22,25], and a mean of 81.62 months in 1 study [7]. There was no significant difference in recurrence rates between immunocompromised and immunocompetent patients with acute colonic diverticulitis (RR, 0.96; 95% CI, 0.70–1.33) (Fig. 6).

9. Postoperative Morbidity after Elective Surgery for Diverticulitis

Four studies reported postoperative morbidities including surgical site infection, wound dehiscence, anastomotic leakage or stenosis, intraabdominal abscess, sepsis, ileus, postoperative bleeding, and cardiovascular, pulmonary, thromboembolic, and renal and urinary tract complications [18,21,22,24]. The rates of postoperative morbidities after elective colonic resection in immunocompromised and immunocompetent patients were 26.6% and 12.3%, respectively. Immunocompromised patients with diverticulitis had a greater risk of postoperative morbidity than immunocompetent patients (RR, 2.07; 95% CI, 1.83–2.34) in the meta-analysis (Z = 11.58, P < 0.00001, I² = 45%) (Fig. 7).

10. Subgroup Analysis by Disease Severity

To examine the clinical outcomes according to disease severity, subgroup analyses were performed. Two studies reported clinical outcomes according to disease severity [7,25]. Severe disease was defined as complicated diverticulitis with an abscess or perforation, and mild disease as diverticulitis without an abscess or perforation.

The risk of emergency surgery following the failure of medical treatment was not significantly different between immunocompromised and immunocompetent patients with mild diverticulitis (RR, 1.13; 95% CI, 0.51–2.50). On the contrary, immunocompromised patients with severe diverticulitis had a greater risk of emergency surgery following failure of medical treatment as compared with their immunocompetent counterparts (55.2% vs. 39.3%; RR, 1.77; 95% CI, 1.10–2.84) (Supplementary Fig. 2).

The risk of recurrence was significantly lower in immunocompromised patients with mild diverticulitis than in immunocompetent patients (RR, 0.50; 95% CI, 0.27–0.91). However, immunocompromised patients with severe diverticulitis showed a greater risk of recurrence as compared with immunocompetent patients (RR, 3.67; 95% CI, 1.58–8.50) (Supplementary Fig. 3).

There was a limitation of this subgroup analysis in that neither study was large. Moreover, the proportion of immunocompromised patients who underwent elective surgery after mild diverticulitis was not clarified in one study [7], which may have affected the recurrence rate.

DISCUSSION

In this systematic review and meta-analysis, immunocompromised patients with diverticulitis had significantly increased risks of surgical intervention, postoperative morbidity, and mortality than immunocompetent patients. Also, the length of hospital stay was longer in immunocompromised than in immunocompetent patients.

Our results support current recommendations that immunocompromised patients with diverticulitis should be treated rigorously. Although recent evidence suggests that antibiotic treatment has no significant benefit in immunocompetent patients with uncomplicated diverticulitis [26,27], it is still recommended for patients with immunosuppression even if there are no complications [10-12]. Additionally, current guidelines recommend that surgeons should maintain a low threshold for surgical intervention in immunocompromised patients with diverticulitis because medical treatment is more likely to fail in such persons [28]. Our results demonstrated that immunocompromised patients had an approximately 1.8-fold increased risk of emergency surgery and a 3.7-fold increased overall risk of death compared with their immunocompetent counterparts. The risk of postoperative mortality after emergency surgery was significantly higher in immunocompromised patients, whereas the risk of postoperative mortality after elective surgery was not significantly different between immunocompromised and immunocompetent patients with diverticulitis. In addition, the risk of complications associated with diverticulitis also tended to increase in immunocompromised patients with diverticulitis, although it was not statistically significant. Furthermore, immunocompromised patients with complicated or severe diverticulitis had increased risks of emergency surgery and recurrence. In one study, when recurrence occurred in patients who had had severe or complicated diverticulitis, severe or complicated disease was repeatedly seen in > 70% irrespective of immune status, and > 20% of these recurrent patients underwent emergency surgery [7]. Therefore, acute diverticulitis in patients with immunosuppression should be recognized as a medical emergency requiring immediate medical attention and multidisciplinary management. Because immunocompromised patients are vulnerable to invasive treatments and have a high risk of death after emergency surgery, they should be given the best nonoperative management unless emergency surgery is unavoidable. Early identification of immunocompromised patients as a high-risk group, prompt evaluation, and early initiation and step-up of antibiotic treatment are required. Meanwhile, in case of complicated or severe diverticulitis, elective surgical intervention can be considered if the patient is medically fit for surgery, because complicated diverticulitis in immunocompromised patients is likely to recur repeatedly as a complicated disease.

However, further discussion is needed on whether aggressive treatment including surgery is essential for immunocompromised patients with mild uncomplicated diverticulitis. Previous studies have shown that there was no significant difference in the outcomes of nonoperative management between immunocompromised and immunocompetent patients with mild uncomplicated diverticulitis [7,25]. Our results also demonstrated that the risk of emergency surgery following failure of medical treatment and the risk of recurrence in mild uncomplicated diverticulitis were not significantly different between immunocompromised and immunocompetent patients, although the results were not robust. Another potential reason why elective surgery is considered unlikely to be necessary in immunocompromised patients with mild uncomplicated diverticulitis is that the overall risk of major morbidity after elective surgery for diverticulitis in immunocompromised patients is more than 2-fold that in immunocompetent patients. Because most included studies did not present treatment outcomes according to disease severity, definite conclusions cannot be drawn from our results. We suggest that immunocompromised patients with mild uncomplicated diverticulitis should receive the best medical treatment and be closely monitored for complications.

There is insufficient evidence on whether immunocompromised patients with diverticulitis are more likely to develop recurrent disease. Our results showed that there was no significant difference in recurrence rates between immunocompromised and immunocompetent patients, although the results were not robust due to the small number of included studies. However, in a subgroup analysis according to disease severity, immunocompromised patients with complicated diverticulitis had a greater risk of recurrence. Current guidelines suggest that patients with immunosuppression should consult a surgeon to discuss elective surgical resection after recovery from an acute episode of diverticulitis especially in complicated cases [12,29,30]. This recommendation seems reasonable because immunocompromised patients are more likely to present with complicated recurrent disease [7,22]. However, it is unclear whether elective surgical resection increases overall survival in immunocompromised patients because they are likely to be frail and have a high risk of postoperative complications [31]. Our results also indicated that immunocompromised patients with diverticulitis had a greater risk of postoperative morbidity after elective surgery than immunocompetent patients. Further research is needed on the long-term survival of immunocompromised patients with diverticulitis who undergo elective surgical resection. The serious clinical impact of recurrence on immunocompromised patients who have not undergone elective surgery after colonic diverticulitis must be carefully considered on a case-by-case basis.

The mechanisms of increased risk of life-threatening diverticulitis in immunocompromised patients are unclear. Plausible explanations include impaired healing leading to bowel perforation, and a lack of immune response that masks symptoms [1]. Immunosuppressive agents have been suggested to impair wound healing and increase the increased risk of wound complications [32,33]. Colonic diverticulitis is thought to arise from complex interactions among diet, lifestyle, genetic factors, and an altered gut microbiome [1]. The pathophysiology of diverticulitis in the immunocompromised settings is uncertain, warranting further research to delineate the mechanisms of developing complicated diverticulitis in immunocompromised patients.

Caution is needed when applying the results of this study to patients with right colonic diverticulitis. Most diverticulitis occurs in the left colon in Western countries. By contrast, most diverticulitis occurs in the right colon in Asia, although the incidence of left-sided diverticulitis has increased in recent years. Previous studies have shown that approximately 80% of colonic diverticulitis is located in the right colon in East Asia [34,35]. Right colonic diverticulitis has a lower risk of complications requiring surgical intervention and a relatively good prognosis than left colonic diverticulitis [36]. Because almost all studies included in this meta-analysis investigated the outcomes of left colonic diverticulitis, the severity and prognosis of right colonic diverticulitis in immunocompromised patients cannot be determined. More data are needed to determine the natural course and prognosis of right colonic diverticulitis in the immunocompromised.

The results of this study can be valuable evidence for medical treatment strategies for immunocompromised patients with diverticulitis. Although a systematic review and meta-analysis on the clinical outcomes of immunocompromised patients with diverticulitis was recently conducted, it assessed the postoperative outcomes in patients who underwent surgical intervention [13]. We quantified not only postoperative outcomes but also overall complication rates, mortality, length of hospital stay, and recurrences in immunocompromised patients with diverticulitis. In addition, we excluded old studies that involved patients with only surgically diagnosed diverticulitis without radiologic examinations, which were likely to have a selection bias of not recruiting patients with mild diverticulitis that did not require surgery or with unknown disease severity [9,37].

This study has several limitations. All included studies were observational, and most were retrospective. Second, the definitions of immunocompromised patients were heterogeneous; patients on immunosuppressive drugs, organ transplant recipients, and those with active extracolonic malignancies, chemotherapy, collagen vascular disease, pulmonary fibrosis, emphysema, end-stage renal disease, and congenital or acquired immunodeficiency syndrome were classified as immunocompromised. Old age itself can be an immunocompromised condition, but it was not considered in the analysis. Because there is no universally accepted definition of immunocompromised patients, there may be inherent flaws in the literature search. Additionally, the difference in clinical outcomes according to the cause of immunosuppression could not be determined. Third, almost all included studies examined the outcomes of left colonic diverticulitis.

Despite these limitations, our findings provide insight into the clinical outcomes of acute colonic diverticulitis in immunocompromised patients. Immunocompromised patients with diverticulitis have greater risks of surgical intervention, postoperative morbidity, and mortality than their immunocompetent counterparts. Early identification, timely evaluation, and the best medical treatment with multidisciplinary approach should be given to immunocompromised patients with acute colonic diverticulitis.

NOTES

Funding Source

The authors received no financial support for the research, authorship, and/or publication of this article.

Conflict of Interest

Park YE, Chang JY, and Kim DK are editorial board members of the journal but were not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.

Data Availability Statement

Not applicable.

Author Contribution

Conceptualization: Kim SE. Data curation: Kim SE, Lee JG. Formal analysis: Kim SE, Lee JG. Methodology: Park YE, Chang JY, Song HJ, Kim DH, Yang YJ, Kim BC, Lee SH, You MW. Supervision: Kim SE. Writing - original draft: Lee JG. Writing - review & editing: Kim SE, Lee JG. Approval of final manuscript: all authors.

Supplementary Material

Supplementary materials are available at the Intestinal Research website (https://www.irjournal.org).

Supplementary Material. Detailed Search Strategy

ir-2023-00005-Supplementary-1.pdf

Supplementary Fig. 1. Risk of bias assessment of included studies.

ir-2023-00005-Supplementary-Fig-1.pdf

Supplementary Fig. 2. Forest plot of emergency surgery following failure of medical treatment according to the disease severity in immunocompromised versus immunocompetent patients with diverticulitis using a fixed-effects model. M-H, Mantel-Haenszel; CI, confidence interval.

ir-2023-00005-Supplementary-Fig-2.pdf

Supplementary Fig. 3. Forest plot of recurrence rate according to the disease severity in immunocompromised versus immunocompetent patients with diverticulitis using a fixed-effects model. M-H, Mantel-Haenszel; CI, confidence interval.

ir-2023-00005-Supplementary-Fig-3.pdf

Fig. 1.

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart.

Fig. 2.

Forest plot of (A) overall need for surgery and (B) emergency surgery in immunocompromised versus immunocompetent patients with acute colonic diverticulitis using a random-effects model. M-H, Mantel-Haenszel; CI, confidence interval.

Fig. 3.

Forest plot of complicated disease of acute colonic diverticulitis in immunocompromised versus immunocompetent patients using a random-effects model. M-H, Mantel-Haenszel; CI, confidence interval.

Fig. 4.

Forest plot of (A) overall mortality and (B) postoperative mortality in immunocompromised versus immunocompetent patients with acute colonic diverticulitis using a random-effects model. M-H, Mantel-Haenszel; CI, confidence interval.

Fig. 5.

Forest plot of length of hospital stay in immunocompromised versus immunocompetent patients with acute colonic diverticulitis using a random-effects model. SD, standard deviation; CI, confidence interval.

Fig. 6.

Forest plot of recurrence rate in immunocompromised versus immunocompetent patients with acute colonic diverticulitis using a fixed-effects model. M-H, Mantel-Haenszel; CI, confidence interval.

Fig. 7.

Forest plot of major morbidity after elective surgery for acute colonic diverticulitis in immunocompromised versus immunocompetent patients using a fixed-effects model. M-H, Mantel-Haenszel; CI, confidence interval.

Table 1.

Characteristics of the Included Studies

Author (year)	Study design	Study period	Definition of immunocompromised patients	No. of patients	Endpoints
Biondo (2012) [7]	Prospective observational study	1994–2008	Immunosuppressant medications	Immunocompromised 166	Need for surgery
			Solid organ transplant	Immunocompetent 765	Complicated disease
			Extracolonic active malignant neoplasm		Complicated disease
			Cytotoxic chemotherapy		Mortality
			Emphysema		Recurrence
			Arthritis and other collagen vascular diseases
			Pulmonary fibrosis
			Congenital or acquired immunodeficiency
Reshef (2012) [18]	Retrospective study	1995–2010	Sold organ transplant recipients	Immunocompromised 51	Postoperative mortality
				Immunocompetent 51	Length of hospital stay
					Overall morbidity
					Reoperation
Cronley (2016) [19]	Cross-sectional study	2007–2011	Patients with HIV infection	Immunocompromised 2,375	Need for surgery
				Immunocompetent 1,160,391	Mortality
				Immunocompetent 1,160,391	Length of hospital stay
Brandl (2016) [8]	Retrospective study	2008–2014	Solid organ transplant	Immunocompromised 15	Need for surgery
			Extracolonic active malignant neoplasm	Immunocompetent 212	Complicated disease
			Collagen vascular diseases		Mortality
			Collagen vascular diseases		Length of hospital stay
Golda (2014) [20]	Retrospective study	2004–2012	Immunosuppressive treatment	Immunocompromised 53	Mortality
			Chronic systemic corticosteroid treatment	Immunocompetent 63	Overall morbidity
			Nonintestinal active malignancy		Reoperation
			End-stage renal failure		Length of hospital stay
			Congenital or acquired immunodeficiency		Length of hospital stay
Al-Khamis (2016) [21]	Retrospective study	2005–2012	Chronic corticosteroid treatment	Immunocompromised 1,332	Mortality
				Immunocompromised 1,332	Overall morbidity
				Immunocompetent 25,655	Reoperation
				Immunocompetent 25,655	Length of hospital stay
Samdani (2014) [22]	Retrospective study	1988–2004	Systemic chemotherapy	Immunocompromised 39	Need for surgery
				Immunocompetent 92	Complicated disease
					Mortality
					Postoperative morbidity
					Length of hospital stay
					Recurrence
Halabi (2013) [23]	Retrospective study	2001–2010	Kidney transplant recipients	Immunocompromised 1,249	Postoperative mortality
Halabi (2013) [23]	Retrospective study	2001–2010	Kidney transplant recipients	Immunocompetent 753,517	Postoperative mortality
Vaghiri (2022) [24]	Retrospective study	2004–2021	Solid organ transplant	Immunocompromised 39	Postoperative mortality
			Congenital or acquired immunodeficiency	Immunocompetent 242	Postoperative morbidity
			Autoimmune diseases requiring immunosuppressive medication	Immunocompetent 242	Length of hospital stay
Sugrue (2018) [25]	Retrospective study	2002–2015	Kidney transplant recipients	Immunocompromised 20	Need for surgery
				Immunocompetent 134	Complicated disease
				Immunocompetent 134	Recurrence

HIV, human immunodeficiency virus.

REFERENCES

1. Strate LL, Morris AM. Epidemiology, pathophysiology, and treatment of diverticulitis. Gastroenterology 2019;156:1282–1298.Article PubMed PMC
2. Bharucha AE, Parthasarathy G, Ditah I, et al. Temporal trends in the incidence and natural history of diverticulitis: a population-based study. Am J Gastroenterol 2015;110:1589–1596.Article PubMed PMC PDF
3. Wheat CL, Strate LL. Trends in hospitalization for diverticulitis and diverticular bleeding in the United States from 2000 to 2010. Clin Gastroenterol Hepatol 2016;14:96–103.Article PubMed PMC
4. Humes DJ, Solaymani-Dodaran M, Fleming KM, Simpson J, Spiller RC, West J. A population-based study of perforated diverticular disease incidence and associated mortality. Gastroenterology 2009;136:1198–1205.Article PubMed
5. Humes DJ, Fleming KM, Spiller RC, West J. Concurrent drug use and the risk of perforated colonic diverticular disease: a population-based case-control study. Gut 2011;60:219–224.Article PubMed
6. Broersen LHA, Horváth-Puhó E, Pereira AM, Erichsen R, Dekkers OM, Sørensen HT. Corticosteroid use and mortality risk in patients with perforated colonic diverticular disease: a population-based cohort study. BMJ Open Gastroenterol 2017;4:e000136.Article PubMed PMC
7. Biondo S, Borao JL, Kreisler E, et al. Recurrence and virulence of colonic diverticulitis in immunocompromised patients. Am J Surg 2012;204:172–179.Article PubMed
8. Brandl A, Kratzer T, Kafka-Ritsch R, et al. Diverticulitis in immunosuppressed patients: a fatal outcome requiring a new approach? Can J Surg 2016;59:254–261.Article PubMed PMC
9. Tyau ES, Prystowsky JB, Joehl RJ, Nahrwold DL. Acute diverticulitis: a complicated problem in the immunocompromised patient. Arch Surg 1991;126:855–858.Article PubMed
10. Peery AF, Shaukat A, Strate LL. AGA clinical practice update on medical management of colonic diverticulitis: expert review. Gastroenterology 2021;160:906–911.Article PubMed PMC
11. Nagata N, Ishii N, Manabe N, et al. Guidelines for colonic diverticular bleeding and colonic diverticulitis: Japan Gastroenterological Association. Digestion 2019;99 Suppl 1:1–26.Article PubMed PDF
12. Sartelli M, Weber DG, Kluger Y, et al. 2020 update of the WSES guidelines for the management of acute colonic diverticulitis in the emergency setting. World J Emerg Surg 2020;15:32.PubMed PMC
13. McKechnie T, Lee Y, Kruse C, et al. Operative management of colonic diverticular disease in the setting of immunosuppression: a systematic review and meta-analysis. Am J Surg 2021;221:72–85.Article PubMed
14. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and metaanalyses: the PRISMA Statement. BMJ 2009;339–b2535.Article
15. Kim SY, Park JE, Lee YJ, et al. Testing a tool for assessing the risk of bias for nonrandomized studies showed moderate reliability and promising validity. J Clin Epidemiol 2013;66:408–414.Article PubMed
16. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557–560.Article PubMed PMC
17. Higgins JPT, Thomas J, Chandler J, et al. Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (updated February 2022) [Internet]. c2022;[cited 2023 Mar 30]. www.training.cochrane.org/handbook.
18. Reshef A, Stocchi L, Kiran RP, et al. Case-matched comparison of perioperative outcomes after surgical treatment of sigmoid diverticulitis in solid organ transplant recipients versus immunocompetent patients. Colorectal Dis 2012;14:1546–1552.Article PubMed
19. Cronley K, Wenzke J, Hussan H, et al. Diverticulitis in HIV-infected patients within the United States. HIV Med 2016;17:216–221.Article PubMed
20. Golda T, Kreisler E, Mercader C, Frago R, Trenti L, Biondo S. Emergency surgery for perforated diverticulitis in the immunosuppressed patient. Colorectal Dis 2014;16:723–731.Article PubMed
21. Al-Khamis A, Abou Khalil J, Demian M, et al. Sigmoid colectomy for acute diverticulitis in immunosuppressed vs immunocompetent patients: outcomes from the ACS-NSQIP database. Dis Colon Rectum 2016;59:101–109.PubMed
22. Samdani T, Pieracci FM, Eachempati SR, et al. Colonic diverticulitis in chemotherapy patients: should operative indications change? A retrospective cohort study Int J Surg 2014;12:1489–1494.PubMed
23. Halabi WJ, Jafari MD, Nguyen VQ, et al. Colorectal surgery in kidney transplant recipients: a decade of trends and outcomes in the United States. Am Surg 2013;79:1026–1033.Article PubMed PDF
24. Vaghiri S, Prassas D, Knoefel WT, Krieg A. Surgical management in immunosuppressed patients with sigmoid diverticulitis, still a challenge: a single-center observational study. Int J Colorectal Dis 2022;37:1909–1917.Article PubMed PMC PDF
25. Sugrue J, Lee J, Warner C, et al. Acute diverticulitis in renal transplant patients: should we treat them differently? Surgery 2018;163:857–865.Article PubMed
26. Chabok A, Påhlman L, Hjern F, Haapaniemi S, Smedh K, AVOD Study Group. Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis. Br J Surg 2012;99:532–539.PubMed
27. Daniels L, Ünlü Ç, de Korte N, et al. Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis. Br J Surg 2017;104:52–61.PubMed
28. Feingold D, Steele SR, Lee S, et al. Practice parameters for the treatment of sigmoid diverticulitis. Dis Colon Rectum 2014;57:284–294.Article PubMed
29. Hall J, Hardiman K, Lee S, et al. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the treatment of left-sided colonic diverticulitis. Dis Colon Rectum 2020;63:728–747.Article PubMed
30. Francis NK, Sylla P, Abou-Khalil M, et al. EAES and SAGES 2018 consensus conference on acute diverticulitis management: evidence-based recommendations for clinical practice. Surg Endosc 2019;33:2726–2741.Article PubMed PMC PDF
31. Coccolini F, Improta M, Sartelli M, et al. Acute abdomen in the immunocompromised patient: WSES, SIS-E, WSIS, AAST, and GAIS guidelines. World J Emerg Surg 2021;16:40.Article PubMed PMC PDF
32. Bootun R. Effects of immunosuppressive therapy on wound healing. Int Wound J 2013;10:98–104.Article PubMed PMC
33. Dean PG, Lund WJ, Larson TS, et al. Wound-healing complications after kidney transplantation: a prospective, randomized comparison of sirolimus and tacrolimus. Transplantation 2004;77:1555–1561.PubMed
34. Yamada E, Ohkubo H, Higurashi T, et al. Visceral obesity as a risk factor for left-sided diverticulitis in Japan: a multicenter retrospective study. Gut Liver 2013;7:532–538.Article PubMed PMC
35. Kim MJ, Woo YS, Kim ER, et al. Is colonoscopy necessary after computed tomography diagnosis of acute diverticulitis? Intest Res 2014;12:221–228.Article PubMed PMC
36. Oh HK, Han EC, Ha HK, et al. Surgical management of colonic diverticular disease: discrepancy between right- and left- sided diseases. World J Gastroenterol 2014;20:10115–10120.Article PubMed PMC
37. Perkins JD, Shield CF 3rd, Chang FC, Farha GJ. Acute diverticulitis: comparison of treatment in immunocompromised and nonimmunocompromised patients. Am J Surg 1984;148:745–748.PubMed

Figure & Data

REFERENCES

Citations

Citations to this article as recorded by

Not all acute colonic diverticulitis follows the same course: a potential risk for immunocompromised individuals
Yehyun Park
Intestinal Research.2023; 21(4): 415. CrossRef

PubReader
ePub Link

Cite

CITE: export Copy Download Format; Close

Download Citation

Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

Format:

RIS — For EndNote, ProCite, RefWorks, and most other reference management software
BibTeX — For JabRef, BibDesk, and other BibTeX-specific software

Include:

Citation for the content below
Citation and abstract for the content below

Comparative outcomes of acute colonic diverticulitis in immunocompromised versus immunocompetent patients: a systematic review and meta-analysis

Intest Res. 2023;21(4):481-492. Published online May 31, 2023

DOI: https://doi.org/10.5217/ir.2023.00005

XML Download

Figure

Related articles

Prevalence of hepatitis B virus and hepatitis C virus infection in patients with inflammatory bowel disease: a systematic review and meta-analysis

Comparative outcomes of acute colonic diverticulitis in immunocompromised versus immunocompetent patients: a systematic review and meta-analysis

Fig. 1. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart.

Fig. 2. Forest plot of (A) overall need for surgery and (B) emergency surgery in immunocompromised versus immunocompetent patients with acute colonic diverticulitis using a random-effects model. M-H, Mantel-Haenszel; CI, confidence interval.

Fig. 3. Forest plot of complicated disease of acute colonic diverticulitis in immunocompromised versus immunocompetent patients using a random-effects model. M-H, Mantel-Haenszel; CI, confidence interval.

Fig. 4. Forest plot of (A) overall mortality and (B) postoperative mortality in immunocompromised versus immunocompetent patients with acute colonic diverticulitis using a random-effects model. M-H, Mantel-Haenszel; CI, confidence interval.

Fig. 5. Forest plot of length of hospital stay in immunocompromised versus immunocompetent patients with acute colonic diverticulitis using a random-effects model. SD, standard deviation; CI, confidence interval.

Fig. 6. Forest plot of recurrence rate in immunocompromised versus immunocompetent patients with acute colonic diverticulitis using a fixed-effects model. M-H, Mantel-Haenszel; CI, confidence interval.

Fig. 7. Forest plot of major morbidity after elective surgery for acute colonic diverticulitis in immunocompromised versus immunocompetent patients using a fixed-effects model. M-H, Mantel-Haenszel; CI, confidence interval.

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Fig. 5.

Fig. 6.

Fig. 7.

Comparative outcomes of acute colonic diverticulitis in immunocompromised versus immunocompetent patients: a systematic review and meta-analysis

Author (year)	Study design	Study period	Definition of immunocompromised patients	No. of patients	Endpoints
Biondo (2012) [7]	Prospective observational study	1994–2008	Immunosuppressant medications	Immunocompromised 166	Need for surgery
			Solid organ transplant	Immunocompetent 765	Complicated disease
			Extracolonic active malignant neoplasm		Complicated disease
			Cytotoxic chemotherapy		Mortality
			Emphysema		Recurrence
			Arthritis and other collagen vascular diseases
			Pulmonary fibrosis
			Congenital or acquired immunodeficiency
Reshef (2012) [18]	Retrospective study	1995–2010	Sold organ transplant recipients	Immunocompromised 51	Postoperative mortality
				Immunocompetent 51	Length of hospital stay
					Overall morbidity
					Reoperation
Cronley (2016) [19]	Cross-sectional study	2007–2011	Patients with HIV infection	Immunocompromised 2,375	Need for surgery
				Immunocompetent 1,160,391	Mortality
				Immunocompetent 1,160,391	Length of hospital stay
Brandl (2016) [8]	Retrospective study	2008–2014	Solid organ transplant	Immunocompromised 15	Need for surgery
			Extracolonic active malignant neoplasm	Immunocompetent 212	Complicated disease
			Collagen vascular diseases		Mortality
			Collagen vascular diseases		Length of hospital stay
Golda (2014) [20]	Retrospective study	2004–2012	Immunosuppressive treatment	Immunocompromised 53	Mortality
			Chronic systemic corticosteroid treatment	Immunocompetent 63	Overall morbidity
			Nonintestinal active malignancy		Reoperation
			End-stage renal failure		Length of hospital stay
			Congenital or acquired immunodeficiency		Length of hospital stay
Al-Khamis (2016) [21]	Retrospective study	2005–2012	Chronic corticosteroid treatment	Immunocompromised 1,332	Mortality
				Immunocompromised 1,332	Overall morbidity
				Immunocompetent 25,655	Reoperation
				Immunocompetent 25,655	Length of hospital stay
Samdani (2014) [22]	Retrospective study	1988–2004	Systemic chemotherapy	Immunocompromised 39	Need for surgery
				Immunocompetent 92	Complicated disease
					Mortality
					Postoperative morbidity
					Length of hospital stay
					Recurrence
Halabi (2013) [23]	Retrospective study	2001–2010	Kidney transplant recipients	Immunocompromised 1,249	Postoperative mortality
Halabi (2013) [23]	Retrospective study	2001–2010	Kidney transplant recipients	Immunocompetent 753,517	Postoperative mortality
Vaghiri (2022) [24]	Retrospective study	2004–2021	Solid organ transplant	Immunocompromised 39	Postoperative mortality
			Congenital or acquired immunodeficiency	Immunocompetent 242	Postoperative morbidity
			Autoimmune diseases requiring immunosuppressive medication	Immunocompetent 242	Length of hospital stay
Sugrue (2018) [25]	Retrospective study	2002–2015	Kidney transplant recipients	Immunocompromised 20	Need for surgery
				Immunocompetent 134	Complicated disease
				Immunocompetent 134	Recurrence

Table 1. Characteristics of the Included Studies

HIV, human immunodeficiency virus.