CD4-positive T cells and M2 macrophages dominate the peritoneal infiltrate of patients with encapsulating peritoneal sclerosis

Background Encapsulating peritoneal sclerosis (EPS) is a severe complication of peritoneal dialysis (PD). Previously, it has been shown that infiltrating CD4-positive T cells and M2 macrophages are associated with several fibrotic conditions. Therefore, the characteristics of the peritoneal cell infiltrate in EPS may be of interest to understand EPS pathogenesis. In this study, we aim to elucidate the composition of the peritoneal cell infiltrate in EPS patients and relate the findings to clinical outcome. Study Design, Setting, and Participants We studied peritoneal membrane biopsies of 23 EPS patients and compared them to biopsies of 15 PD patients without EPS. The cellular infiltrate was characterized by immunohistochemistry to detect T cells(CD3-positive), CD4-positive (CD4+) and CD8-positive T cell subsets, B cells(CD20-positive), granulocytes(CD15-positive), macrophages(CD68-positive), M1(CD80-positive), and M2(CD163-positive) macrophages. Tissues were analysed using digital image analysis. Kaplan-Meier survival analysis was performed to investigate the survival in the different staining groups. Results The cellular infiltrate in EPS biopsies was dominated by mononuclear cells. For both CD3 and CD68, the median percentage of area stained was higher in biopsies of EPS as opposed to non-EPS patients (p<0.001). EPS biopsies showed a higher percentage of area stained for CD4 (1.29%(0.61-3.20)) compared to CD8 (0.71%(0.46-1.01), p = 0.04), while in the non-EPS group these cells were almost equally represented (respectively 0.28% (0.05-0.83) versus 0.22%(0.17-0.43), p = 0.97). The percentage of area stained for both CD80 and CD163 was higher in EPS than in non-EPS biopsies (p<0.001), with CD163+ cells being the most abundant phenotype. Virtually no CD20-positive and CD15-positive cells were present in biopsies of a subgroup of EPS patients. No relation was found between the composition of the mononuclear cell infiltrate and clinical outcome. Conclusions A characteristic mononuclear cell infiltrate consisting of CD4+ and CD163+ cells dominates the peritoneum of EPS patients. These findings suggest a role for both CD4+ T cells and M2 macrophages in the pathogenesis of EPS

CD4-positive T cells and M2 macrophages dominate the peritoneal infiltrate of patients with encapsulating peritoneal sclerosis

Background: Encapsulating peritoneal sclerosis (EPS) is a severe complication of peritoneal dialysis (PD). Previously, it has been shown that infiltrating CD4-positive T cells and M2 macrophages are associated with several fibrotic conditions. Therefore, the characteristics of the peritoneal cell infiltrate in EPS may be of interest to understand EPS pathogenesis. In this study, we aim to elucidate the composition of the peritoneal cell infiltrate in EPS patients and relate the findings to clinical outcome. Study Design, Setting, and Participants: We studied peritoneal membrane biopsies of 23 EPS patients and compared them to biopsies of 15 PD patients without EPS. The cellular infiltrate was characterized by immunohistochemistry to detect T cells(CD3-positive), CD4-positive (CD4+) and CD8-positive T cell subsets, B cells(CD20-positive), granulocytes(CD15-positive), macrophages(CD68-positive), M1(CD80-positive), and M2(CD163-positive) macrophages. Tissues were analysed using digital image analysis. Kaplan-Meier survival analysis was performed to investigate the survival in the different staining groups. Results: The cellular infiltrate in EPS biopsies was dominated by mononuclear cells. For both CD3 and CD68, the median percentage of area stained was higher in biopsies of EPS as opposed to non-EPS patients (p<0.001). EPS biopsies showed a higher percentage of area stained for CD4 (1.29%(0.61-3.20)) compared to CD8 (0.71%(0.46-1.01), p = 0.04), while in the non-EPS group these cells were almost equally represented (respectively 0.28%(0.05-0.83) versus 0.22%(0.17-0.43), p = 0.97). The percentage of area stained for both CD80 and CD163 was higher in EPS than in non-EPS biopsies (p<0.001), with CD163+cells being the most abundant phenotype. Virtually no CD20-positive and CD15-positive cells were present in biopsies of a subgroup of EPS patients. No relation was found between the composition of the mononuclear cell infiltrate and clinical outcome. Conclusions: A characteristic mononuclear cell infiltrate consisting of CD4+ and CD163+ cells dominates the peritoneum of EPS patients. These findings suggest a role for both CD4+ T cells and M2 macrophages in the pathogenesis of EPS

A multicenter randomized clinical trial investigating the cost-effectiveness of treatment strategies with or without antibiotics for uncomplicated acute diverticulitis (DIABOLO trial)

Background. Conservative treatment of uncomplicated or mild diverticulitis usually includes antibiotic therapy. It is, however, uncertain whether patients with acute diverticulitis indeed benefit from antibiotics. In most guidelines issued by professional organizations antibiotics are considered mandatory in the treatment of mild diverticulitis. This advice lacks evidence and is merely based on experts' opinion. Adverse effects of the use of antibiotics are well known, including allergic reactions, development of bacterial resistance to antibiotics and other side-effects. Methods. A randomized multicenter pragmatic clinical trial comparin

2013 WSES guidelines for management of intra-abdominal infections

Peer reviewe

Encapsulating peritoneal sclerosis: the state of affairs

Encapsulating peritoneal sclerosis (EPS) is a severe complication of long-term peritoneal dialysis (PD) with a 50% mortality rate. EPS is characterized by progressive and excessive fibrotic thickening of the peritoneum, leading to encapsulation of the bowels and intestinal obstruction. At present, EPS cannot be detected with certainty during its early stages; however, a progressive loss of ultrafiltration capacity often precedes its development. Studies that attempted to elucidate the pathogenesis of EPS have shown that the duration of exposure to PD fluids is the most important risk factor for EPS, and that young age and possibly the effects of peritonitis are additional contributory factors. The pathophysiology of EPS is probably best described as a multiple-hit process with a central role for transforming growth factor β. A form of EPS that develops shortly after kidney transplantation has also been recognized as a distinct clinical entity, and may be a common form of EPS in countries with a high transplantation rate. Criteria have been developed to identify EPS by abdominal CT scan at the symptomatic stage, but further clinical research is needed to identify early EPS in asymptomatic patients, to clarify additional risk factors for EPS and to define optimal treatment strategie

Localized encapsulating peritoneal sclerosis constricting the terminal ileum-an unusual appearance requiring surgical intervention

Background: Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis (PD). It is characterized by encapsulation of the bowel, causing symptoms of intestinal obstruction. Exclusive involvement of parts of the bowel may occur and may be more common than previously thought. Our main objective was to investigate and report on patients with localized EPS. Methods: Between July 2002 and December 2011, 9 of 17 EPS patients were referred to our department of surgery for a diagnostic laparotomy. Three of the 9 cases showed localized encapsulation of the small bowel and were selected for the purpose of this study. Results: All 3 patients presented with an acute inflammatory state and symptoms of bowel obstruction. In 2 patients, EPS became clinically overt after kidney transplantation; the third patient was diagnosed while on hemodialysis. All shared a history of PD ranging from 31 to 101 months. In none of the patients was radiologic examination conclusive, although 2 showed peritoneal thickening and ascites. Each patient underwent laparotomy, confirming EPS. In all cases, a thickened peritoneal membrane became apparent, predominantly covering the ileocecal region of the intestine. In addition, a constrictive membrane at the level of the terminal ileum was noted. In 2 cases, the patients underwent enterolysis and dissection of the constricting fibrotic peritoneal membrane (peritonectomy) without bowel resection. The 3rd patient was managed with parenteral nutrition and tamoxifen. The postoperative course in 1 patient was complicated by infected ascites that resolved with antibiotic treatment. Eventually, all patients

Tamoxifen is associated with lower mortality of encapsulating peritoneal sclerosis: results of the Dutch Multicentre EPS Study

Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis (PD) with an increasing incidence. There is no clear consensus on the treatment of EPS, but anecdotal reports indicate improvement in EPS patients treated with tamoxifen. At present, there is no evidence for the effect of tamoxifen treatment in EPS patients. This study investigates the effect of treatment with tamoxifen on survival in EPS patients. This study is a retrospective analysis of survival in EPS patients as part of the Dutch multicentre EPS study in the period January 1996 to July 2007. Sixty-three patients with severe EPS were followed up until August 2008. Demographic, patient and PD-related variables of EPS patients were investigated. Patients treated with tamoxifen were compared to patients not treated with tamoxifen. Survival was analysed with multivariate Cox regression analysis. Twenty-four patients were treated with tamoxifen, and 39 were not treated with tamoxifen. The clinical and demographic characteristics were similar for the tamoxifen-treated and non-treated groups. The mortality rate was significantly lower in tamoxifen-treated patients compared to EPS patients not treated with tamoxifen (45.8% vs 74.4%, P=0.03). Survival in tamoxifen-treated patients, adjusted for calendar time, age, use of corticosteroids, presence of functioning transplantation, use of parental nutrition and centre influences was longer in comparison to not-treated patients (HR 0.39, P=0.056). Tamoxifen treatment in EPS patients is associated with lower mortality and shows a trend to an increased multivariate-adjusted survival. This supports additional use of tamoxifen to treat patients with severe EP