Pathophysiology of encapsulating peritoneal sclerosis: lessons from findings of the past three decades in Japan.

Encapsulating peritoneal sclerosis (EPS), a condition with a high mortality rate, is a serious complication of peritoneal dialysis (PD). In Japan, EPS became a central issue in the clinical setting during the mid-90s and the beginning of this century. However, following the introduction of biocompatible neutral PD solutions containing lower levels of glucose degradation products, the incidence and clinical severity of EPS has been greatly lessened. During the past three decades, the etiology of EPS has been elucidated by findings obtained by peritoneal biopsy, laparoscopy, and surgical intervention. Accumulating findings suggest the need for a paradigm change on the nature of EPS pathophysiology; notably, EPS appears not to reflect peritoneal sclerosis per se, but rather the formation of a neo-membrane as a biological reaction to peritoneal injury. This narrative review looks back on the history of EPS in Japan, and discusses EPS pathophysiology, the impact of neutral PD solution on peritoneal protection, and a future novel diagnostic approach, ultra-fine endoscope, for the identification of patients at high risk of EPS.

A case of cyclic hemoperitoneum in a hemodialysis patient: Encapsulated peritoneal sclerosis complicated by endometriosis and fungal peritonitis.

Encapsulated peritoneal sclerosis (EPS) is a rare, but frequently fatal, long-term complication of peritoneal dialysis. Endometriosis is a common gynecological problem but hemoperitoneum due to endometriosis has been reported to be extremely rare in hemodialysis (HD) patients. A 25-year-old female HD patient was admitted to our clinic with nausea, vomiting, abdominal pain, and weight loss for last 3 months. Candida tropicalis and Candida glabrata were isolated in the fungal cultures from peritoneal fluid. Her abdominal computerized tomography scan has shown irregular peritoneal calcifications, diffuse peritoneal thickening, dilatation of the small bowel loops, and cocoon formation which all were typical for EPS. Hemoperitoneum was reported to recur for four times with intervals suggesting menstrual cycles. Her peritoneal biopsy, along with the signs of EPS, has also revealed the presence of endometriosis. The patient died with symptoms of septic shock in the first year of EPS diagnosis.

Recent Understanding of Peritoneal Pathology in Peritoneal Dialysis Patients in Japan.

The thin peritoneum covering the peritoneal cavity has been used as a dialysis membrane for peritoneal dialysis (PD) because it is highly vascularized and has a large body surface area. However, it has been reported that peritoneal membranes affected by peritonitis, as well as those exposed to the nonphysiological high glucose levels containing PD dialysate, may undergo histological and functional changes. Patients undergoing PD may experience encapsulating peritoneal sclerosis (EPS), which is a life-threatening serious complication of PD that can significantly impair activities of daily living. The incidence of EPS was 1.4-7.3% of maintenance PD patients in the 1980s. The incidence has improved to 1.0% after a neutral dialysate became the standard PD treatment in Japan. Furthermore, the pathogenesis of EPS is uncertain although its onset may be explained by the "two-hit theory," in which some factors leading to impairment had an additive effect on simple peritoneal sclerosis. The evaluation of histopathological findings has shown the impact of the neutral dialysate on peritoneal deterioration as well as its role in the development of functional changes. In the present report, we discuss the advances in the understanding of peritoneal deterioration based on histological and macroscopic evaluations of the peritoneum of patients undergoing PD. We also discuss the recent treatment for PD patients.

Clinical risk factors and outcomes of massive ascites accumulation after discontinuation of peritoneal dialysis.

Background: Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis (PD), with high morbidity and mortality that requires an early diagnosis for effective treatment. PD withdrawal and bacterial peritonitis are important triggers for the onset of EPS. However, few studies have focused on cases of PD withdrawal without a clinical diagnosis of peritonitis, cirrhosis, or carcinomatosis. We aimed to compare the clinical characteristics and computed tomography (CT) images of patients with or without ascites in such situations and assess clinical outcomes in terms of mortality.Methods: Our retrospective review included 78 patients who withdraw PD between January 2000 and December 2017.Results: Ten patients had ascites, and 68 did not have a significant intra-abdominal collection. The ascites group had a significantly longer PD duration (months; 134.41 [range, 35.43-181.80] vs. 32.42 [733-183.47], p < 0.001) and higher peritoneal membrane transport status based on the dialysate-to-plasma ratios of creatinine (0.78 ± 0.08 vs. 0.68 ± 0.11, p = 0.009) and glucose (0.27 ± 0.07 vs. 0.636 ± 0.08, p = 0.001) than the control group. CT parameters, including peritoneal calcification, thickness, bowel tethering, or bowel dilatation, were not all present in each patient with ascites and EPS. During the 12-month study period, the ascites group had a higher risk for developing EPS (70% vs. 0%, p < 0.001) and a higher 12-month all-cause mortality (30% vs. 0%, p = 0.002).Conclusions: Ascites accumulation was not rare after PD discontinuation. A longer PD duration and high peritoneal membrane transport status could predict subsequent ascites accumulation. Furthermore, patients with ascites were at a higher risk of EPS.

A Successful Treatment of Encapsulating Peritoneal Sclerosis in an Adolescent Boy on Long-term Peritoneal Dialysis: A Case Report.

Encapsulating peritoneal sclerosis (EPS) is a rare life-threatening complication associated with peritoneal dialysis (PD). EPS is characterized by progressive fibrosis and sclerosis of the peritoneum, with the formation of a membrane and tethering of loops of the small intestine resulting in intestinal obstruction. It is very rare in children. We present a case of a 16-year-old adolescent boy who developed EPS seven years after being placed on continuous ambulatory peritoneal dialysis (CAPD) complicated by several episodes of bacterial peritonitis. The diagnosis was based on clinical, radiological, intraoperative and histopathological findings. The patient was successfully treated with surgical enterolysis. During a 7-year follow-up, there have been no further episodes of small bowel obstruction documented. He still continues to be on regular hemodialysis and is awaiting a deceased donor kidney transplant. EPS is a long-term complication of peritoneal dialysis and is typically seen in adults. Rare cases may be seen in the pediatric population and require an appropriate surgical approach that is effective and lifesaving for these patients.

Encapsulating sclerosing peritonitis : two rare observations and literature review.

Sclerosing encapsulating peritonitis (SEP) is a rare and little known pathological entity. It is a chronic fibro-inflammatory disease of the peritoneum, resulting in the formation of a thick fibrous membrane, which engages partially or totally the abdominal organs. Clinical and radiological signs make the diagnosis difficult to establish preoperatively. We present two original observations of SEP illustrating different clinical presentations, diagnostic and therapeutic means. His diagnosis requires a peritoneal biopsy. The treatment is not completely established. Surgical treatment is difficult, involving viscerolysis and multiple incisions of the fibrous membrane. Despite the current progress in therapeutic management, the prognosis remains pejorative, with significant mortality.

A prospective, proteomics study identified potential biomarkers of encapsulating peritoneal sclerosis in peritoneal effluent.

Encapsulating peritoneal sclerosis (EPS) is a potentially devastating complication of peritoneal dialysis (PD). Diagnosis is often delayed due to the lack of effective and accurate diagnostic tools. We therefore examined peritoneal effluent for potential biomarkers that could predict or confirm the diagnosis of EPS and would be valuable in stratifying at-risk patients and driving appropriate interventions. Using prospectively collected samples from the Global Fluid Study and a cohort of Greek PD patients, we utilized 2D SDSPAGE/ MS and iTRAQ to identify changes in the peritoneal effluent proteome from patients diagnosed with EPS and controls matched for treatment exposure. We employed a combinatorial peptide ligand library to compress the dynamic range of protein concentrations to aid identification of low-abundance proteins. In patients with stable membrane function, fibrinogen γ-chain and heparan sulphate proteoglycan core protein progressively increased over time on PD. In patients who developed EPS, collagen-α1(I), γ-actin and Complement factors B and I were elevated up to five years prior to diagnosis. Orosomucoid-1 and a2-HS-glycoprotein chain-B were elevated about one year before diagnosis, while apolipoprotein A-IV and α1-antitrypsin were decreased compared to controls. Dynamic range compression resulted in an increased number of proteins detected with improved resolution of protein spots, compared to the full fluid proteome. Intelectin-1, dermatopontin, gelsolin, and retinol binding protein-4 were elevated in proteome-mined samples from patients with EPS compared to patients that had just commenced peritoneal dialysis. Thus, prospective analysis of peritoneal effluent uncovered proteins indicative of inflammatory and pro-fibrotic injury worthy of further evaluation as diagnostic/prognostic markers.

Clinical signs of fibrosis in small intestinal neuroendocrine tumours.

BACKGROUND: In patients with small intestinal neuroendocrine tumours (SI-NETs), serotonin and other cytokines released from tumour cells may induce fibrosis, leading to carcinoid heart disease and abdominal fibrotic reactions. The aim of this study was to assess the prevalence, clinical complications and management of this reaction in the abdomen. METHODS: This was a retrospective cohort study of patients with SI-NETs diagnosed between 1985 and 2015. Clinical data, outcomes, radiological findings, and surgical and radiological interventions were reviewed. RESULTS: A total of 824 patients were diagnosed with SI-NETs in the study interval. Clinically significant abdominal signs and symptoms of fibrosis occurred in 36 patients. Of these, 20 had critically symptomatic central mesenteric fibrosis causing obstruction of mesenteric vessels, and 16 had retroperitoneal fibrosis causing obstructive uropathy with hydronephrosis. Extensive fibrosis causing mesenteric vessel obstruction and/or obstructive uropathy was more often associated with symptomatic and advanced disease encompassing lymph node metastases in the mesenteric root, para-aortic lymph node metastases, as well as liver metastases and peritoneal carcinomatosis. Palliative intervention in terms of superior mesenteric vein stenting or resection of central mesenteric metastases and/or percutaneous nephrostomy and J stent treatment was beneficial in the majority of the patients. CONCLUSION: Extensive abdominal fibrosis associated with clinically significant symptoms of intestinal ischaemia and/or obstructive uropathy was linked to advanced disease in patients with SI-NETs. Prompt recognition and minimally invasive intervention was effective in disease palliation.

Diagnosis and Treatment of 26 Cases of Abdominal Cocoon.

BACKGROUND AND AIMS: Abdominal cocoon (AC) is a rare abdominal disease with nonspecific clinical features, and it is difficult to be diagnosed before operation and hard to be treated in clinical practice. The aim of this study is to investigate the diagnosis and treatment of AC. METHODS: The clinical manifestations, findings during surgery, treatments, and follow-up results of 26 cases of AC were retrospectively studied from January 2001 to January 2015. RESULTS: All of 26 cases were diagnosed as AC definitely by laparotomy or laparoscopic surgery. Their clinical findings were various, with 7 intestines obstructed with bezoars and 4 intestines perforated by spiny material. Based on the existence of the second enterocoelia, all cases were categorized into 2 types: type I is absent of second enterocoelia (18 cases, 69.23%), while type II shows second enterocoelia (8 cases, 30.77%). Twenty cases (12 were type I and 8 were type II) underwent membrane excision and careful enterodialysis to release the small intestine entirely or partially, while the other 6 cases (all were type I) did not. In addition, all patients were treated with medical treatment and healthy diet and lifestyle. Finally, most of the patients recovered smoothly. CONCLUSIONS: AC can be categorized into two types; surgery is recommended for type II and part of type I with severe complications, but sometimes conservative therapy might be appropriate for type I. Laparoscopic surgery plays an important role in the diagnosis and treatment of AC. Furthermore, favorite health education, healthy diet and lifestyle are of significance in patients' recovery.

Case report: acute bowel obstruction with an isolated transition point in peritoneal dialysis patients; a presentation of encapsulating peritoneal sclerosis?

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is classically described as progressive sclerosis and cocooning of the entire peritoneum; however, there has been limited number of reported cases of localized fibrosis as a variant form. CASE PRESENTATION: We describe two cases of acute bowel obstruction with isolated transition points in the setting of long-term peritoneal dialysis. CONCLUSION: We postulate that some of the cases of small bowel obstruction with an obvious transition point in long-term peritoneal dialysis patients may represent a unique and localized form of EPS. We aim to emphasize the presence of macroscopic variations in presentation of EPS.

The enigma of primary and secondary encapsulating peritoneal sclerosis.

BACKGROUND: Encapsulating Peritoneal Sclerosis (EPS) describes a variety of diseases that are frequently confused with different names and different etiopathogeneses. The aim of this article is to report personal experience of focusing on correct classification and the status of current diagnosis and treatment. METHODS: A retrospective analysis was performed. Age, sex, ethnic origin, past medical history, symptoms and their duration, radiological tools and signs, laboratory tests, preoperative diagnosis, surgical approach, intraoperative findings, pathological findings, hospital stay, morbidity and mortality were studied. RESULTS: A total of seven patients, including six males and one female, aged from 24 to 72 years were observed. Four patients had recurrent abdominal colic pain for 3 months, 1, 2 and 9 years; two patients also reported recurrent attacks but without any specification of the duration. All seven patients presented at the emergency department with abdominal pain that was mainly diffused over the entire abdomen. Six patients were submitted to a CT scan. Only in two patients was the diagnosis of EPS made preoperatively. All seven patients were submitted to open surgery. The hospital stay was between 4 and 60 days. One patient had morbidity, and one patient died of MOF. CONCLUSIONS: Currently, the correct identification of EPS is more easily possible than in the past, but the diagnosis is still a challenge. Surgery must be performed as soon as possible to avoid a poorer quality of life.

Peritoneal effluent MMP-2 and PAI-1 in encapsulating peritoneal sclerosis.

BACKGROUND: Recently, the use of effluent matrix metalloproteinase 2 (MMP-2) and plasminogen activator inhibitor 1 (PAI-1) as potential biomarkers of peritoneal fibrosis has been demonstrated during longitudinal follow-up of incident peritoneal dialysis (PD) patients. This study focuses on effluent MMP-2 and PAI-1 as early diagnostic markers in the preceding years of patients who develop encapsulating peritoneal sclerosis (EPS). STUDY DESIGN: Diagnostic test study. SETTINGS & PARTICIPANTS: PD patients who developed EPS were compared with controls using a 1:3 case-control design with a minimum PD duration of 57 months. INDEX TESTS: Dialysate appearance rates of MMP-2 and PAI-1. REFERENCE TEST: EPS cases identified by 2 experienced nephrologists and a radiologist based on predefined criteria. RESULTS: 11 patients developed EPS within our center. The time course of MMP-2 appearance rates, studied by means of a linear repeated-measures model 4 years prior to the diagnosis of EPS, showed no difference between long-term controls and patients with EPS. In contrast, higher PAI-1 appearance rates were found in patients with EPS compared with controls (P=0.01). At a lag time of 1 year prior to EPS diagnosis, time-specific receiver operating characteristic curve analyses indicated a discriminative ability for PAI-1 appearance rate of 0.77 (95% CI, 0.63-0.91). A discriminative capacity was absent for those of MMP-2. LIMITATIONS: Low event rate of EPS prevented independent validation in this single-center study. CONCLUSIONS: Elevated levels of PAI-1 appearance rates are present in patients who develop EPS, pointing to progressive peritoneal fibrosis and sclerosis. The PAI-1 appearance rate has fair discriminative capacity from 3 years prior to EPS diagnosis. Therefore, effluent PAI-1 may aid in monitoring peritoneal fibrosis and serve as a biomarker for EPS.

Late presentation of encapsulating peritoneal sclerosis following renal transplantation and the potential under-reporting of the incidence and prevalence of encapsulating peritoneal sclerosis.

Encapsulating peritoneal sclerosis is an infrequent but potentially devastating complication of peritoneal dialysis. The reported incidence and prevalence of encapsulating peritoneal sclerosis vary markedly between countries. Currently, peritoneal dialysis vintage remains the major risk factor for encapsulating peritoneal sclerosis, and dialysis vintage differs between countries due to the relative competing risks of transplantation, availability of haemodialysis and peritonitis. However, the diagnosis of encapsulating peritoneal sclerosis is often only established when patients have transferred modality to transplantation or haemodialysis. Switching treatment modality may potentially lead to an under-reporting of encapsulating peritoneal sclerosis, as many countries which collect data on dialysis patients in national registries often have separate registries for dialysis and transplant patients, and this may potentially lead to under-reporting of encapsulating peritoneal sclerosis in patients presenting after renal transplantation. Secondly, the question arises as to how long former peritoneal dialysis patients should be followed before a diagnosis of encapsulating peritoneal sclerosis can be confidently excluded. To highlight this point, we present four cases that developed symptomatic encapsulating peritoneal sclerosis more than 5 years, and in once case more than 10 years after the discontinuation of peritoneal dialysis. Delayed or late presentation may not only delay the diagnosis, but also risk surgical interventions by non-specialists. A more robust system is required to record cases of encapsulating peritoneal sclerosis to determine the incidence and prevalence, and so provide accurate information to both patients and clinicians as to the risks of long-term peritoneal dialysis therapy.

Encapsulating peritoneal sclerosis in children.

Encapsulating peritoneal sclerosis (EPS) is a rare but extremely serious complication of peritoneal dialysis (PD). While EPS has been well recognized in adults on long-term PD, and children can spend many years on PD before a transplant becomes available, only a small number of children with EPS have been described. Two European pediatric registries have recently reported on the prevalence, potential risk factors and outcomes of EPS in children. Although the prevalence of EPS is comparable to that published in adult registries, the outcome of pediatric EPS is significantly better and carries a lower mortality. All studies have shown a greater risk of EPS with a longer dialysis vintage, but it is not known why some individuals are susceptible to EPS development. In this review we discuss current views on the epidemiology, pathogenesis and management strategies for EPS. The hope of the authors is that this review will alert pediatric nephrologists to this rare but extremely serious complication of chronic PD. In the future, collaborative research and the establishment of a pediatric EPS registry may be of importance in helping pediatric nephrologists to recognize the early warning signs of EPS development and thereby to develop strategies for its prevention and optimal management.

Dialysate cancer antigen 125 in long-term peritoneal dialysis patients.

Structural and functional peritoneal membrane changes are associated with long-term peritoneal dialysis. These changes can lead to ultrafiltration failure and peritoneal fibrosis, reducing the efficacy of the peritoneal membrane to remove waste and balance fluid and electrolytes. The loss of mesothelial cells from the basement membrane is one of the major characteristics in peritoneal membrane structural change. Thus, if the reduction of peritoneal mesothelial cell mass in peritoneal dialysis patients is monitored, signs of ultrafiltration failure and peritoneal fibrosis can be detected early. One of biomarkers that can be used to indicate the change in peritoneal mesothelial cell mass is CA125, which is produced by mesothelial cells. In this article, we review the measurement and clinical use of CA125 in peritoneal dialysate effluent. Additionally, we address the data and studies on the association between dialysate CA125 levels and factors related to ultrafiltration failure and peritoneal fibrosis, including the parameters used to monitor the functional status of the peritoneal membrane. Our review shows that dialysate CA125 can be used to evaluate the peritoneal membrane in noninfected patients to predict peritoneal fibrosis, and it can also be used as a biomarker of biocompatible dialysis solutions.

Successful surgical approach for a patient with encapsulating peritoneal sclerosis after hyperthermic intraperitoneal chemotherapy: a case report and literature review.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare surgical complication that can occur after intraperitoneal treatment. It is also a serious and potentially fatal complication of continuous ambulatory peritoneal dialysis. The present report describes a case of surgically treated EPS that probably occurred as a complication of hyperthermic intraperitonal chemotherapy (HIPEC). CASE PRESENTATION: A 39-year-old man required sigmoidectomy for serosal invasive advanced sigmoid colon cancer. HIPEC with oxaliplatin, 5-fluorouracil and mitomycin C were given as adjuvant therapy. Subsequently, intestinal obstruction developed at 15 months postoperatively, and the patient was hospitalized. Abdominal computed tomography showed a dilated small intestine enveloped by a thickened membrane. We found no evidence of peritoneal recurrence, but exploratory surgery revealed EPS, probably caused by HIPEC. We peeled the capsule off of the intestine. The patient's postoperative course was uneventful, and sufficient nutritional intake after surgery was noted. Seven months after surgery, he is well with no recurrence. CONCLUSION: The surgical treatment via peritonectomy and enterolysis for postoperative EPS appears safe and effective. A diagnosis of EPS should be considered when intestinal obstruction does not show improvement with conservative treatment in patients who have undergone HIPEC, provided the possibility of peritoneal cancer recurrence is excluded.

The value of osmotic conductance and free water transport in the prediction of encapsulating peritoneal sclerosis.

Qualitative assessments in long-term patients and in those with encapsulating peritoneal sclerosis (EPS) have shown that impaired osmotic conductance is likely a factor contributing to the presence of ultrafiltration failure in those individuals. In the present study, we investigated the value of osmotic conductance, its components LpA and the reflection coefficient sigma, and free water transport (FWT) in 12 patients with EPS, in 21 patients with long-term ultrafiltration failure, and in 26 time-restricted control subjects with normal ultrafiltration. A decrease in all parameters was observed during a period of 4 years in patients with EPS and ultrafiltration failure, with FWT showing the largest difference between all three groups; however, the receiver operating curves showed that only FWT appeared to be a significant predictor of EPS. Because its measurement is simple, FWT should be included in the regular assessment of peritoneal function.

Weekly intraperitoneal steroid infusion to treat recurrent ascites in a patient with early stage of peritoneal dialysis-related encapsulating peritoneal sclerosis: A case report.

Encapsulating peritoneal sclerosis (EPS) is a rare and potentially fatal complication of long-term peritoneal dialysis (PD). EPS-induced large volume and recurrent ascites represents a challenging condition. We report a 51-year-old man with kidney failure treated with PD for 13 years who eventually developed early stage of EPS accompanied with poor intake and recurrent ascites. After management including discontinuing PD and switching to haemodialysis, as well as oral steroids and tamoxifen administration, the patient had refractory ascites. An intervention of weekly intraperitoneal steroid infusion with methylprednisolone was implemented for a year. Gradually, we observed a reduction in ascites drainage, an improvement of clinical symptoms and the patient's nutritional status. The PD catheter was successfully removed as there was no recurrence of ascites. Intraperitoneal corticosteroid administration represents a new intervention for patients with early stage of EPS and recurrent ascites after PD cessation.