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Abstract

Objective

This study aimed to evaluate the effect of surgical versus nonsurgical treatment on mortality in patients with encapsulating peritoneal sclerosis who underwent peritoneal dialysis.

Methods

A comprehensive search using PubMed, Google Scholar, MEDLINE, Science Direct, Scopus, and CNKI databases was conducted to extract relevant data based on predefined inclusion criteria. RevMan5.2 was applied to analyze and compare the effect of surgical versus nonsurgical treatment on mortality in patients with encapsulating peritoneal sclerosis who underwent peritoneal dialysis.

Results

A total of 7 studies involving 70 surgical and 57 nonsurgical patients were included, with 61.4% females and 38.6% males. Among them, 69 were Asian and 58 were European patients, with 37.7% and 75.9% of Asian and European patients accepting surgical treatment, respectively. Pooled data analysis indicated that surgical treatment was associated with significantly lower mortality than nonsurgical treatment in patients with encapsulating peritoneal sclerosis (odds ratio = 0.25, 95% confidence interval: 0.11–0.57, Z = 3.29; P = 0.001). Subgroup analysis revealed that Asian patients who accepted surgical treatment had significantly lower mortality than those receiving nonsurgical treatment (odds ratio = 0.19, 95% confidence interval: 0.06–0.57, Z = 2.93; P = 0.003), whereas no significant difference was observed in mortality between surgical and nonsurgical treatments in European patients (odds ratio = 0.38, 95% confidence interval: 0.10–1.41, Z = 1.45; P = 0.15).

Conclusions

Surgical treatment was associated with reduced mortality in patients with encapsulating peritoneal sclerosis compared with nonsurgical treatment; however, this benefit was more significant in Asian patients than in European patients.

Keywords

Peritoneal dialysis encapsulating peritoneal sclerosis surgery mortality meta-analysis

Background

Peritoneal dialysis (PD) has emerged as a well-established renal replacement treatment modality.¹ Encapsulating peritoneal sclerosis (EPS), also known as abdominal cocoon syndrome or sclerosing encapsulating peritonitis, is a debilitating condition characterized by a fibrocollagenous membrane encasing the small intestine, resulting in recurrent small bowel obstructions.^2,3 EPS is associated with high morbidity and mortality, primarily due to bowel obstruction resulting in intestinal failure, malnutrition, and sepsis.⁴ The risk of EPS is strongly correlated with the duration of PD treatment and its eventual cessation.⁵ The diagnosis of EPS is based on a triad of clinical, radiological, and histopathological findings.⁴ The clinical symptoms of EPS include nausea, vomiting, and abdominal pain, all of which appear to be associated with bowel obstruction.⁴ The disease is frequently progressive and can be fatal. Computed tomography is considered the gold standard imaging modality for the detection of peritoneal abnormalities and encapsulation of bowel loops with thick adhesions or fibrosis.⁴ Common treatment options for EPS include the combined use of immunosuppressants and surgery.⁶ Intra-abdominal adhesions are common and can lead to intestinal obstruction; thus, surgical intervention is mainly based on enterolysis, which is a form of adhesiolysis.⁷ Among patients on PD, 50%–80% will develop peritoneal fibrosis, and 0.5%–4.4% will develop life-threatening EPS.⁸ The actuarial survival rates at 1, 5, and 8 years after EPS diagnosis are 91%, 66%, and 53%, respectively. Furthermore, the 50% actuarial survival times after EPS diagnosis and surgery are 104 and 85 months, respectively.⁹ Despite these findings, there is no consensus on the role of surgical intervention in the treatment of EPS. Several studies have reported divergent outcomes in mortality between surgical and nonsurgical treatment of EPS in patients undergoing PD. To elucidate the correlation between surgical intervention and mortality, we conducted a comprehensive literature search and performed a meta-analysis of relevant studies.

Information and methodology

This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, which provided a standardized framework for transparent reporting of meta-analyses.

We had not prospectively registered this trial; however, we have registered it retrospectively at Research Registry (registration number: reviewregistry1963).

Screening and searching for literature

A systematic search of PubMed, Google Scholar, MEDLINE, Science Direct, Scopus, and CNKI databases was conducted, without restrictions on language or publication date. The search strategy combined MeSH terms and free-text words, including “Peritoneal Dialysis,” “Encapsulating Peritoneal Sclerosis,” “Operative,” and “Mortality.” Keywords including “peritoneal dialysis,” “abdominal cocoon,” “encapsulating peritoneal sclerosis,” “encapsulated peritoneal sclerosis,” “sclerosing encapsulating peritonitis,” “surgical,” and “mortality” were used to retrieve all potential studies. The search strategy was as follows: (((peritoneal dialysis) AND (abdominal cocoon)) AND (operation)) AND (mortality), (((peritoneal dialysis) AND (encapsulating peritoneal sclerosis)) AND (operation)) AND (mortality), (((peritoneal dialysis) AND (encapsulated peritoneal sclerosis)) AND (operation)) AND (mortality) and (((peritoneal dialysis) AND (sclerosing encapsulating peritonitis)) AND (operation)) AND (mortality). We subsequently reviewed the abstracts and titles of the relevant studies identified. By examining the full texts, we determined the studies eligible for inclusion in the analysis. The inclusion criteria of the meta-analysis were as follows: (a) studies with “Clinical Study” as the study type; (b) studies involving patients with confirmed diagnosis of EPS after undergoing PD; (c) studies analyzing surgical treatment, use of immunosuppressants, and sex; and (d) controlled studies in which patients were clearly classified by survivor/death groups. The exclusion criteria were as follows: (a) case series, editorials, and letters to the editor; (b) articles with incomplete data; (c) studies with small sample sizes (n < 5); and (d) studies with a lack of surgical expertise (the operator had insufficient prior exposure to the surgical technique).

Data extraction

Three authors separately extracted the data. In case of any disagreement, they discussed the study selection process to reach a consensus. The extracted data included the following information: (a) general information: first author, location of the study sample, total number of study samples, and research methodology; (b) demographic information: country and sex; (c) mode of intervention: surgery and drugs; and (d) death data.

Quality evaluation

The Newcastle–Ottawa Scale (NOS) was used to evaluate the methodological quality of all studies included in this systematic review. Three reviewers independently assessed the methodological qualities of each study, and the results were compared subsequently (Table 1).

Table 1.

Newcastle–Ottawa score of the included studies.

Study ID	Exposed cohort (representative)	Non exposed cohort selected from the same source	Exposure ascertained	Outcome of study was not present at start of the study	Comparability	Adequate assessment	Follow-up was long enough	Adequate follow-up	Quality score
Toyohara et al.²⁰	★	★	★	★	★	★	★	★	8
Latus et al.¹¹	★	★	★	★	★ ★	★	★	★	9
Yamahatsu et al.¹²	★	★	★	★	★	★			6
Tseng et al.¹³	★	★	★	★	★	★	★	★	8
Hong et al.¹⁴	★	★	★	★	★	★	★		7
Messina et al.²¹	★	★	★	★	★	★	★		7
Courtney and Doherty²²	★	★	★	★	★	★	★	★	8

The Newcastle–Ottawa scale comprises a total of 8 items. The maximum possible score is 9 stars (★), and studies achieving 7 stars or above are considered high-quality.

Statistical analysis

RevMan5.2 (The Cochrane Collaboration, Oxford, UK) was used to analyze the data. The results of the meta-analysis were presented as odds ratios (OR) with 95% confidence intervals (CIs). A P-value <0.05 was considered to indicate statistical significance. Heterogeneity was assessed using the I² statistic or a P-value of <0.05. If the I² value was <50% or P-value was >0.05, indicating no significant heterogeneity, a fixed-effects model was applied. Otherwise, potential sources of heterogeneity were explored. A random-effects model was utilized for the meta-analysis if no cause of heterogeneity could be identified and no clinical heterogeneity was observed among the studies.

Results

Basic information

The literature screening process is illustrated in Figure 1. A total of nine studies were included, all of which were retrospective studies (Table 2). Heterogeneity analyses indicated the presence of heterogeneity. After case-by-case exclusion, the heterogeneity was found to originate from the study by Ryu et al.¹⁰ The article suggested that relatively poor outcomes in our series were mainly attributed to the small study cohort and limited cumulative experience of EPS surgical cases at our center. The study by Bozan et al. was excluded due to its small sample size of only four cases.⁷ A total of 7 studies involving 127 cases were included in the data analysis, comprising 70 cases in the surgery group and 57 cases in the nonsurgery group.

Figure 1.

Flowchart of the literature search and study selection.

Table 2.

Characteristics of the included studies in the meta-analysis.

Author	Year	Region	EPS	Surgery	Operation method	Surgical death	Cause of death	No surgery	Number of patients who died
Toyohara et al.²⁰	2011	Japan	15	4	Adhesiolysis	2	Ileus	11	5
Latus et al.¹¹	2012	Germany	42	31	Adhesiolysis	6	Sepsis	11	3
Yamahatsu et al.¹²	2005	Japan	13	4	Adhesiolysis	1	GI bleed	9	6
Tseng et al.¹³	2018	China	23	8	Adhesiolysis	2	Sepsis	15	15
Hong et al.¹⁴	2013	Korea	8	1	Adhesiolysis	0	–	7	4
Messina et al.²¹	2015	Italy	10	9	Adhesiolysis	3	Sepsis	1	1
Courtney and Doherty²²	2005	UK	16	13	Adhesiolysis	5	Sepsis	3	3

EPS: encapsulating peritoneal sclerosis, GI: gastrointestinal

A fixed-effects model was selected as no heterogeneity was observed among the included studies. The pooled data indicated that patients with EPS who accepted surgical treatment had lower mortality than those receiving nonsurgical treatment (OR = 0.25, 95% CI: 0.11–0.57, Z = 3.29; P = 0.001) (Figure 2). Based on their geographical origin, the studies were categorized into Asian and European studies. The analysis revealed that 69 (54.3%) patients in the Asian group developed EPS after PD, 37.7% of whom underwent surgical treatment. A subgroup analysis indicated that Asian patients who accepted surgical treatment had lower mortality than those who were managed nonsurgically (OR = 0.19, 95% CI: 0.06–0.57, Z = 2.93; P = 0.003) (Figure 2). The analysis revealed that 58 (45.7%) patients in the European group developed EPS after PD, 75.9% of whom underwent surgical treatment. A subgroup analysis indicated that the mortality of European patients who accepted surgical treatment was not significantly different from that of European patients who were managed nonsurgically (OR = 0.38, 95% CI: 0.10–1.41, Z = 1.45; P = 0.15) (Figure 2). Among the seven included studies, studies by Latus et al.,¹¹ Yamahatsu et al.,¹² Tseng et al.,¹³ and Hong et al.¹⁴ did not report the sex of the patients who died following surgery and were therefore excluded from the analysis. The results of the remaining studies indicated no significant variation in the impact of sex on mortality among patients who accepted surgical treatment (OR = 0.49, 95% CI: 0.09–2.55, Z = 0.85; P = 0.39) (Figure 3). Studies by Latus et al.,¹¹ Tseng et al.,¹³ and Hong et al.¹⁴ failed to report the use of immunosuppressants in patients who died and were therefore excluded from the analysis. The results of the remaining studies indicated that there was no distinction in the impact of the combined use of immunosuppressants on mortality among patients who accepted surgical treatment (OR = 0.26, 95% CI: 0.09–1.06, Z = 1.88; P = 0.29) (Figure 3).

Figure 2.

Comparison of mortality between surgical and nonsurgical treatment of patients with encapsulating peritoneal sclerosis (EPS) who underwent peritoneal dialysis (PD).

Figure 3.

Comparison of the effect of (a) sex and (b) use of immunosuppressants on mortality in patients who accepted surgery.

Analysis of bias

Funnel plots were constructed using the data, with the horizontal coordinate representing the effect size (corresponding to the OR for each study), where an OR value >1 indicates that the factor was a risk factor. The vertical coordinate represented the standard error (SE (log OR)), where larger sample sizes corresponded to smaller standard errors and a distribution closer to the top of the plot. The vertical line in the middle of the funnel plot represented the combined OR, and ideal studies should have been evenly distributed on both sides of the vertical line. No significant asymmetry was observed in any of the studies included in this analysis, indicating no significant bias in this study (Figure 4).

Figure 4.

Funnel plot of surgery in patients with encapsulating peritoneal sclerosis (EPS) who underwent peritoneal dialysis (PD) in the fixed-effects model: surgery and nonsurgery (control).

Discussion

EPS is a rare, life-threatening, and serious complication of long-term PD. No evidence-based management strategy has been established to date.¹⁵ The common treatments for EPS include the combined use of immunosuppressants and surgery⁶; however, the immunosuppressive agents have not yet been fully elucidated.¹⁶ EPS is a debilitating condition characterized by a fibrocollagenous membrane encasing the small intestine, resulting in recurrent small bowel obstructions. EPS is most commonly associated with long-term PD, although medications, peritoneal infections, and systemic inflammatory disorders have been implicated.³ Many cases remain idiopathic.³ Currently, surgical intervention is the most effective treatment for EPS, as it offers the only viable solution to the problem of fibrocollagenous membrane encapsulation.¹⁷ To gain a more accurate understanding of the correlation between surgery and mortality, we conducted a comprehensive search of relevant studies and performed a meta-analysis.

A total of 7 studies involving 70 surgical and 57 nonsurgical patients were included, with 61.4% females and 38.6% males. Among them, 69 were Asian and 58 were European patients. Surgical treatment was accepted by 37.7% of Asian patients and 75.9% of European patients, which may reflect differences in healthcare access and patient awareness between regions. The study by Latus et al.,¹¹ which revealed that most of the patients in the patient cohort were male and the published data about sex as a risk factor for the development of EPS were variable, was excluded from this study. Of the remaining 85 patients, 38.6% were male and 61.4% were female, supporting the finding that EPS is more prevalent in females. The study by Tseng et al.¹³ was excluded due to insufficient data on immunosuppressants use. Among these patients, 45.2% were treated with immunosuppressants, whereas 54.8% were not. The lower use of immunosuppressants may be attributed to the ongoing debate regarding their efficacy or the limited sample size of this study.

The current study revealed that patients with EPS who underwent surgical treatment had lower mortality than those who received nonsurgical treatment, which is consistent with a previous study involving 130 patients. In the abovementioned study, the surgical technique of enterolysis successfully treated >92% of the patients, with a postoperative mortality rate of 6.9%. The results demonstrated that patients with EPS who undergo surgical intervention can achieve improved survival rates.¹⁸ A subgroup analysis revealed that among patients who underwent surgical treatment, no significant variation was noted in the impact of sex on mortality. This may be attributed to the small sample size included in our study, and further research with larger datasets is needed to confirm this finding. Some studies have suggested that the use of immunosuppressants is associated with a more favorable prognosis for surgical patients with EPS¹⁹; the results of our study do not support this conclusion. Our study found no significant difference in mortality among patients who underwent surgical treatment, with or without the combined use of immunosuppressants. This discrepancy may be attributed to the long time span of the included studies, during which some samples were collected in an earlier period when immunosuppressive therapy for EPS was not yet standardized or when the dose of immunosuppressants varied. These factors could have contributed to inconsistent effects and influenced the observed mortality.¹⁸

This study also had several limitations. The available sample size in this meta-analysis was relatively small, both across domestic and international studies. The willingness of patients with EPS to undergo surgery, their postoperative recovery, and the treatment approaches before and after surgery in Asia and Europe are influenced by differences in local policies and medical standards. Furthermore, factors such as ethnicity, culture, and diet may play a role, which cannot be overlooked. These aspects require further research for confirmation.

In conclusion, surgical intervention should be considered as a treatment option for patients with EPS who underwent PD, particularly in cases where surgery is indicated, such as intestinal obstruction. Enterolysis is the primary surgical method, and the procedure should be performed as early as possible to prevent sepsis caused by intestinal obstruction, which poses a significant threat to the patient’s life and surgical prognosis.

Footnotes

Acknowledgements

None.

Author contribution

Wei Huan and Gan Wenyuan conducted literature review and conceived the study. Liu Changxuan and Chen Wenli revised the manuscript critically for important intellectual content. Wei Huan wrote the first draft of the manuscript.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Data availability

The data of this study can be availed upon reasonable request.

Declaration of conflicting interest

The authors declare that there is no conflict of interest.

Ethical considerations

The article is a synthesis of several independent analyses of clinical studies to quantify and identify unelucidated issues and search for new hypotheses and research ideas. There are no concerns of human or animal safety or privacy involved.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

ORCID iD

Wei Huan

References

Teitelbaum

Peritoneal Dialysis. N Engl J Med 2021; 385: 1786–1795.

Lasheen

ElKorety

Abdominal cocoon or encapsulating peritoneal sclerosis: a rare cause of small bowel obstruction. Eur J Case Rep Intern Med 2020; 7: 001972.

Danford

Lin

Smith

, et al. Encapsulating peritoneal sclerosis. World J Gastroenterol 2018; 24: 3101–3111.

Srisajjakul

Prapaisilp

Bangchokdee

Imaging pearls and differential diagnosis of encapsulating peritoneal sclerosis: emphasis on computed tomography. Clin Imaging 2023; 94: 116–124.

Ryckelynck

Bechade

Bouvier

, et al. Encapsulating peritoneal sclerosis. Nephrol Ther 2017; 13: 211–219.

Moinuddin

Wang

Fullwood

, et al. Renal hyperparathyroidism- a risk factor in the development of encapsulating peritoneal sclerosis. Front Endocrinol (Lausanne) 2024; 15: 1282925.

Bozan

Kanat

Yazar

, et al. A diagnostic dilemma for acute abdomen: sclerosing encapsulating peritonitis (abdominal cocoon syndrome); a retrospective cohort study. Arch Iran Med 2021; 24: 447–452.

Szebeni

Veres-Szekely

Pap

, et al. Extracellular vesicles of patients on peritoneal dialysis inhibit the TGF-beta- and PDGF-B-mediated fibrotic processes. Cells 2024; 1313: 605.

Kawanishi

Banshodani

Yamashita

, et al. Surgical treatment for encapsulating peritoneal sclerosis: 24 years' experience. Perit Dial Int 2019; 39: 169–174.

10.

Ryu

Lee

Koo

, et al. Outcomes of the surgical management of encapsulating peritoneal sclerosis: a case series from a single center in Korea. Kidney Res Clin Pract 2019; 38: 499–508.

11.

Latus

Ulmer

Fritz

, et al. Encapsulating peritoneal sclerosis: a rare, serious but potentially curable complication of peritoneal dialysis-experience of a referral centre in Germany. Nephrol Dial Transplant 2013; 28: 1021–1030.

12.

Yamahatsu

Hamada

Kaneko

, et al. Long-term outcome of encapsulating peritoneal sclerosis (EPS) patients in a single center. Clin Exp Nephrol 2015; 19: 961–967.

13.

Tseng

Chen

Wang

, et al. Incidence and outcomes of encapsulating peritoneal sclerosis (EPS) and factors associated with severe EPS. PLoS One 2018; 13: e0190079.

14.

Hong

Bae

Jang

, et al. Encapsulating peritoneal sclerosis: case series from a university center. Korean J Intern Med 2013; 28: 587–593.

15.

Al-Lawati

Al Shaibi

Al Mahruqi

, et al. Encapsulating peritoneal sclerosis: a case report and literature review. Am J Case Rep 2020; 21: e925341.

16.

Liakopoulos

Georgianos

Vaios

, et al. 10-year-long survival in a PD patient with severe calcifying encapsulating peritoneal sclerosis treated with tamoxifen: a case-report. BMC Nephrol 2020; 21: 110.

17.

Kawanishi

Surgical and medical treatments of encapsulation peritoneal sclerosis. Contrib Nephrol 2012; 177: 38–47.

18.

Kawanishi

Ide

Yamashita

, et al. Surgical techniques for prevention of recurrence after total enterolysis in encapsulating peritoneal sclerosis. Adv Perit Dial 2008; 24: 51–55.

19.

Lafrance

Letourneau

Ouimet

, et al. Successful treatment of encapsulating peritoneal sclerosis with immunosuppressive therapy. Am J Kidney Dis 2008; 51: e7–10.

20.

Toyohara

Ubara

Higa

, et al. Prognosis of patients on continuous ambulatory peritoneal dialysis (CAPD) for over 10 years. Intern Med 2011; 50: 2519–2523.

21.

Messina

Ariaudo

Mella

, et al. mTOR inhibitors for medical treatment of post-transplantation encapsulating peritoneal sclerosis: a favourable single center experience. J Nephrol 2015; 28: 245–249.

22.

Courtney

Doherty

CC.

Single-center experience of encapsulating peritoneal sclerosis in patients on peritoneal dialysis for end-stage renal failure. Kidney Int 2006; 69: 1094.

Effect of surgery for encapsulating peritoneal sclerosis on mortality in patients undergoing peritoneal dialysis: A meta-analysis

Abstract

Objective

Methods

Results

Conclusions

Keywords

Background

Information and methodology

Screening and searching for literature

Data extraction

Quality evaluation

Statistical analysis

Results

Basic information

Analysis of bias

Discussion

Footnotes

Acknowledgements

Author contribution

Consent to participate

Consent for publication

Data availability

Declaration of conflicting interest

Ethical considerations

Funding

ORCID iD

References