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A healthy and functional peritoneal membrane is key to achieving sufficient ultrafiltration and restoring fluid balance, a major component of high-quality prescription in patients treated with peritoneal dialysis (PD). Variability in membrane function at the start of PD or changes over time on treatment influence dialysis prescription and outcomes, and dysfunction of the peritoneal membrane contributes to fluid overload and associated complications. In this review, we summarize the current knowledge about the structure, function, and pathophysiology of the peritoneal membrane with a focus on clinical implications for patient-centered care. We also discuss the molecular and genetic mechanisms of solute and water transport across the peritoneal membrane, including the role of aquaporin water channels in crystalloid versus colloid osmosis; why and how to assess membrane function using peritoneal equilibration tests; the etiologies of membrane dysfunction and their specific management; and the effect of genetic variation on membrane function and outcomes in patients treated with PD. This review also identifies the gaps in current knowledge and perspectives for future research to improve our understanding of the peritoneal membrane and, ultimately, the care of patients treated with PD., (Copyright © 2023 by the American Society of Nephrology.)

Introduction: Malignant mesothelioma is an aggressive neoplasm arising from serosal lining and has a poor prognosis. Definite diagnosis requires confirmation through a biopsy; however, it is sometimes difficult on microscopic evaluation alone and requires the use of a wide panel of immunohistochemical markers. So, immunohistochemistry (IHC) is of paramount importance and must be routinely used for a definite diagnosis. Till date, very few studies on morphology and detailed IHC markers of mesothelioma have been reported from India., Aims: To analyze the histomorphological findings of malignant mesothelioma, study the utility and role of the various immunohistochemical markers., Material and Methods: A total of 76 cases of mesotheliomas diagnosed at a tertiary cancer center in Udaipur were analyzed retrospectively from January 2015 to January 2020. Comprehensive data were analyzed including demographic, clinical, radiological, histopathological features along with a wide panel of IHC markers., Results: Mesothelioma occurs over a wide age range from 40 to 70 years. It most commonly involved pleura in 68 cases (89.47%) with very few cases from the peritoneum. On computed tomography (CT) scan, nodular pleural or peritoneal thickening was present. On microscopy, the most common histopathological type was epithelioid mesothelioma (58 cases, 74.3%) followed by sarcomatous (9 cases, 12.8%), deciduoid (6 cases, 8.6%), and 3 cases of biphasic (4.3%). On IHC, WT1, mesothelin, and calretinin markers were positive in 85.91%, 80%, and 93.33% cases of mesothelioma, respectively. Other markers were helpful to rule out differential diagnosis in difficult scenarios., Conclusion: Therefore, the correlation of histopathology with clinico-radiological findings and judicious use of a panel of IHC markers is required for routine evaluation and definite diagnosis. IHC is also useful in situations with similar morphological spectrum in specific locations.

Sclerosing encapsulating peritonitis is a very rare pathological entity. It is a chronic fibroinflammatory disease affecting the peritoneum and leading to the formation of diffuse egg-shell-shaped fibrous capsule which totally or locally encapsulate the abdominal viscera, in particular the digestive tract. Clinical signs are little specific and misleading. Medical imaging, including computed tomography, can help clinicians to make a diagnosis, by highlighting a thin peritoneal membrane encompassing an agglutination of digestive loops. Secondary types (postperitoneal dialysis, tuberculosis, medications, postintraperitoneal chemotherapy) are quite common, however idiopathic sclerosing encapsulating peritonitis is very rare and few cases have been reported in the literature. We here report the case of a 53-year-old woman with idiopathic sclerosing encapsulating peritonitis., Competing Interests: Les auteurs ne déclarent aucun conflit d'intérêts, (Copyright: Nizar El Bouardi et al.)

Peritoneal hydatid cysts are rare in children even in endemic areas. The primary or secondary origin of this site remains controversial, especially in children. Secondary peritoneal hydatid cysts are mainly the result of spontaneous or traumatic rupture of concomitant liver cysts or the leakage of cystic content during surgery. The purpose of our study is to present the largest case series of peritoneal hydatidosis in children. In addition, we aimed to assess the clinical and paraclinical findings as well as the management of echinococcosis at this location in children. The present case series is a study of ten children with peritoneal hydatid cysts, who underwent surgical intervention between 2013 and 2018 in the Pediatric Surgery Department, University of Monastir (Monastir, Tunisia). The mean age of the children was six years. All children presented abdominal pain, and underwent ultrasonography and contrast-enhanced computed tomography of the abdomen. Two patients had been operated on for lung hydatid cysts six months prior to the study. In two cases, radiologic investigations revealed the presence of an uncomplicated hepatic hydatid cyst located in segments II and IV. All patients underwent surgery, of which four underwent laparoscopy. Post-surgery, all patients received albendazole for three months, and the follow-up period was uneventful. Currently, all patients are in good health. Peritoneal hydatid disease is frequently secondary to the rupture of a primary hepatic cyst. Diagnosis is performed by abdominal ultrasound, computed tomography, and a positive serology result. Open or laparoscopic excision can be combined with medical treatment., Competing Interests: Conflict of Interest: None declared., (Copyright: © Iranian Journal of Medical Sciences.)

The extracellular matrix (ECM) plays critical roles in tumor progression and metastasis. However, the contribution of ECM proteins to early metastatic onset in the peritoneal cavity remains unexplored. Here, we suggest a new route of metastasis through the interaction of integrin alpha 2 (ITGA2) with collagens enriched in the tumor coinciding with poor outcome in patients with ovarian cancer. Using multiple gene-edited cell lines and patient-derived samples, we demonstrate that ITGA2 triggers cancer cell adhesion to collagen, promotes cell migration, anoikis resistance, mesothelial clearance, and peritoneal metastasis in vitro and in vivo. Mechanistically, phosphoproteomics identify an ITGA2-dependent phosphorylation of focal adhesion kinase and mitogen-activated protein kinase pathway leading to enhanced oncogenic properties. Consequently, specific inhibition of ITGA2-mediated cancer cell-collagen interaction or targeting focal adhesion signaling may present an opportunity for therapeutic intervention of metastatic spread in ovarian cancer., Competing Interests: YH, CL, DR, RC, DS, ME, CC, NR, AS, MN, AF, MK, TV, DC, CL, LD, BR, FJ, VH No competing interests declared, (© 2020, Huang et al.)

Different measures of rates of transfer of glucose during the peritoneal equilibrium test (PET), undertaken during peritoneal dialysis (PD) might provide additional information regarding a patient's risk of future cardiovascular mortality. This study aimed to characterize the heterogeneity of dialysate glucose (DG) response phenotypes during the PET and compare the cardiovascular mortality rates associated with the different phenotypes. Our cohort was derived from Henan peritoneal dialysis registry. A total of 3477 patients initiating PD in 2007 to 2014 had the DG measured at 0, 2-hour and 4-hour (D0, D2, and D4 respectively) during the PET for estimation of D2/D0 and D4/D0. Deaths mainly due to CVD within 2 years since the initiation of PD were defined as the outcome. Latent class mixed-effect models were fitted to identify distinct phenotypes of the DG response during the PET. Multivariable unconditional Logistic regression models with adjustment for cardiometabolic risk factors were used to compare the 2-year risk of cardiovascular mortality among patients in the different latent classes. Three distinct DG response phenotypes during the PET were identified. Those with consistently high D2/D0 and D4/D0 ratios had a 1.22 [95% confidence interval: 1.02, 1.35] excess risk of a cardiovascular death within 2 years of commencing PD compared with patients with the lowest D2/D0 ratio and decreased D4/D0 ratio after adjustment for cardiometabolic risk factors. Consistently elevated D2/D0 and D4/D0 ratios during the PET are associated with an increased risk of 2-year cardiovascular mortality independent of other cardiometabolic risk factors. In view of the potential bias due to unmeasured confounders (eg, Family history of cardiovascular diseases, and dietary patterns), this association should be further validated in other external cohorts.

The role of intra-peritoneal mediators in the regulation peritoneal transport is not completely understood. We investigate the relation between longitudinal changes in dialysis effluent level of nuclear factor kappa-B (NF-κB) downstream mediators and the change in peritoneal transport over 1 year. We studied 46 incident PD patients. Their peritoneal transport characteristics were determined after starting PD and then one year later. Concomitant dialysis effluent levels of interleukin-6 (IL-6), cyclo-oxygenase-2 (COX-2) and hepatocyte growth factor (HGF) are determined. There were significant correlations between baseline and one-year dialysis effluent IL-6 and COX-2 levels with the corresponding dialysate-to-plasma creatinine level at 4 hours (D/P4) and mass transfer area coefficient of creatinine (MTAC). After one year, patients who had peritonitis had higher dialysis effluent IL-6 (26.6 ± 17.4 vs 15.1 ± 12.3 pg/ml, p = 0.037) and COX-2 levels (4.97 ± 6.25 vs 1.60 ± 1.53 ng/ml, p = 0.007) than those without peritonitis, and the number of peritonitis episode significantly correlated with the IL-6 and COX-2 levels after one year. In contrast, dialysis effluent HGF level did not correlate with peritoneal transport. There was no difference in any mediator level between patients receiving conventional and low glucose degradation product solutions. Dialysis effluent IL-6 and COX-2 levels correlate with the concomitant D/P4 and MTAC of creatinine. IL-6 and COX-2 may contribute to the short-term regulation of peritoneal transport.

Purpose: Superficial peritoneal endometriotic (pEM) lesions are composed of endometrial glands and stroma, in addition to a third component-myofibroblasts and smooth muscles (SM)-like cells. The latter develops secondary to a metaplasia. In this study, we characterised the third component cells in pEM according to differentiation markers in different micro-compartments. Furthermore, a possible effect of TGFβ1 on myofibroblastic metaplasia in endometriotic epithelial cells was studied., Methods: Seventy-six premenopausal patients were included. Peritoneal biopsies were excised from EM patients (n = 23), unaffected peritoneum (peritoneum from EM patients but without EM components, n = 5/23) and non-EM patients (n = 10). All peritoneal biopsies were immunolabeled for ASMA, calponin, collagen I, desmin, TGFß receptor 1 (R1), R2 and R3 in addition to ultrastructure examination by transmission electron microscopy (TEM) (n = 1). TGFß1 level was measured in peritoneal fluid (PF) (EM, n = 19 and non-EM, n = 13) collected during laparoscopy. Furthermore, TGFß1 effect on myofibroblastic metaplasia was studied in vitro., Results: At the centre of pEM lesions, calponin immunolabeling outweighs the collagen I while in the periphery the reverse occurs. SM-like cells expressing desmin predominate at the periphery, while ASMA immunolabeling was detectable in all micro-compartments. Both indicate an abundance of myofibroblasts at the centre of pEM lesions and SM-like cells in the periphery. Although activated TGFß1 in PF did not differ between EM and non-EM, it inhibited the cell proliferation of the endometriotic epithelial cells and induced an upregulation in ASMA and collagen IA2 expression as well., Conclusion: The abundance of the myofibroblasts and SM-like cells points to a myofibroblastic metaplasia in pEM. Both cells are differentially arranged in the different micro-compartments of pEM lesions, with increasing cell maturity towards the periphery of the lesion. Furthermore, TGFß1 may play a role in the myofibroblastic metaplasia of the endometriotic epithelial cells. These findings provide a better insight in the micro-milieu in EM lesions, where most of the disease dynamics occur.

Peritoneal membrane failure (PMF) and, ultimately, encapsulating peritoneal sclerosis (EPS) are the most serious peritoneal dialysis (PD) complications. Combining clinical and peritoneal transport data with the measurement of molecular biomarkers, such as the chemokine CCL18, would improve the complex diagnosis and management of PMF. We measured CCL18 levels in 43 patients' effluent and serum at baseline and after 1, 2, and 3 years of PD treatment by retrospective longitudinal study, and evaluated their association with PMF/EPS development and peritoneal risk factors. To confirm the trends observed in the longitudinal study, a cross-sectional study was performed on 61 isolated samples from long-term (more than 3 years) patients treated with PD. We observed that the patients with no membrane dysfunction showed sustained low CCL18 levels in peritoneal effluent over time. An increase in CCL18 levels at any time was predictive of PMF development (final CCL18 increase over baseline, p = .014; and maximum CCL18 increase, p = .039). At year 3 of PD, CCL18 values in effluent under 3.15 ng/ml showed an 89.5% negative predictive value, and higher levels were associated with later PMF (odds ratio 4.3; 95% CI 0.90-20.89; p = .067). Moreover, CCL18 levels in effluent at year 3 of PD were independently associated with a risk of PMF development, adjusted for the classical (water and creatinine) peritoneal transport parameters. These trends were confirmed in a cross-sectional study of 61 long-term patients treated with PD. In conclusion, our study shows the diagnostic capacity of chemokine CCL18 levels in peritoneal effluent to predict PMF and suggests CCL18 as a new marker and mediator of this serious condition as well as a new potential therapeutic target.

Objectives: To assess the incidence of testicular appendices (Tas), epididymal anomalies (EAs), and processus vaginalis (PV) patency in patients with undescended testis (UT) according to testicular position and to compare them with human fetuses., Methods: We studied 85 patients (108 testes) with cryptorchidism and compared the features with those of 15 fetuses (30 testes) with scrotal testes. We analyzed the relationships among the testis and epididymis, patency of PV, and the presence of TAs. We used the Chi-square test for statistical analysis ( p < 0.05)., Results: In 108 UT, 72 (66.66%) had PV patent, 67 (62.03%) had TAs, and 39 (36.12%) had EAs. Of the 108 UT, 14 were abdominal (12.96%; 14 had PV patency, 9 TAs, and 7 EAs); 81 were inguinal (75%; 52 had PV patency, 45 TAs, and 31 EAs), and 13 were suprascrotal (12.03%; 6 had PV patency, 13 TAs, and 1 EAs). The patency of PV was more frequently associated with EAs ( p = 0.00364). The EAs had a higher prevalence in UT compared with fetuses ( p = 0.0005)., Conclusions: Undescended testis has a higher risk of anatomical anomalies and the testes situated in abdomen and inguinal canal have a higher risk of presenting patency of PV and EAs.

The mesothelium was traditionally thought to be a simple tissue with the sole function of providing a slippery, nonadhesive, and protective surface to allow easy movement of organs within their body cavities. However, our knowledge of mesothelial cell physiology is rapidly expanding, and the mesothelium is now recognized as a dynamic cellular membrane with many other important functions. When injured, mesothelial cells initiate a cascade of processes leading either to complete regeneration of the mesothelium or the development of pathologies such as adhesions. Normal mesothelial healing is unique in that, unlike with other epithelial-like surfaces, healing appears diffusely across the denuded surface, whereas for epithelium healing occurs solely at the wound edges. This is because of a free-floating population of mesothelial cells which attach to the injured serosa. Taking advantage of this phenomenon, intraperitoneal injections of mesothelial cells have been assessed for their ability to prevent adhesion formation. This review discusses some of the functions of mesothelial cells regarding maintenance of serosal integrity and outlines the mechanisms involved in mesothelial healing. In addition, the pathogenesis of adhesion formation is discussed with particular attention to the potential role of mesothelial cells in both preventing and inducing their development., (Copyright © 2016. Published by Elsevier Inc.)

Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death worldwide. Besides the lymphatic and haematogenous routes of dissemination, CRC frequently gives rise to transcoelomic spread of tumor cells in the peritoneal cavity, which ultimately leads to peritoneal carcinomatosis (PC). PC is associated with a poor prognosis and bad quality of life for these patients in their terminal stages of disease. A loco-regional treatment modality for PC combining cytoreductive surgery and hyperthermic intraperitoneal peroperative chemotherapy has resulted in promising clinical results. However, this novel approach is associated with significant morbidity and mortality. A comprehensive understanding of the molecular events involved in peritoneal disease spread is paramount in avoiding unnecessary toxicity. The emergence of PC is the result of a molecular crosstalk between cancer cells and host elements, involving several well-defined steps, together known as the peritoneal metastatic cascade. Individual or clumps of tumor cells detach from the primary tumor, gain access to the peritoneal cavity and become susceptible to the regular peritoneal transport. They attach to the distant peritoneum, subsequently invade the subperitoneal space, where angiogenesis sustains proliferation and enables further metastatic growth. These molecular events are not isolated events but rather a continuous and interdependent process. In this manuscript, we review current data regarding the molecular mechanisms underlying the development of colorectal PC, with a special focus on the peritoneum and the role of the surgeon in peritoneal disease spread., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interest for this article.

Unlabelled: ♦, Background: Peritoneal dialysis (PD) patients develop progressive and cumulative peritoneal injury with longer time spent on PD. The present study aimed to a) describe the trend of peritoneal injury biomarkers, matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1), in incident PD patients, b) to explore the capacity of dialysate MMP-2 to predict peritoneal solute transport rate (PSTR) and peritonitis, and c) to evaluate the influence of neutral pH, low glucose degradation product (GDP) PD solution on these outcomes. ♦, Methods: The study included 178 participants from the balANZ trial who had at least 1 stored dialysate sample. Changes in PSTR and peritonitis were primary outcome measures, and the utility of MMP-2 in predicting these outcomes was analyzed using multilevel linear regression and multilevel Poisson regression, respectively. ♦, Results: Significant linear increases in dialysate MMP-2 and TIMP-1 concentrations were observed (p < 0.001), but neither was affected by the type of PD solutions received (MMP-2: p = 0.07; TIMP-1: p = 0.63). An increase in PSTR from baseline was associated with higher levels of MMP-2 (p = 0.02), and the use of standard solutions over longer PD duration (p = 0.001). The risk of peritonitis was independently predicted by higher dialysate MMP-2 levels (incidence rate ratio [IRR] per ng/mL 1.01, 95% confidence interval [CI] 1.005 - 1.02, p = 0.002) and use of standard solutions (Biocompatible solution: IRR 0.45, 95% CI 0.24 - 0.85, p = 0.01). ♦, Conclusion: Dialysate MMP-2 and TIMP-1 concentrations increased with longer PD duration. Higher MMP-2 levels were associated with faster PSTR and future peritonitis risk. Administration of biocompatible solutions exerted no significant effect on dialysate levels of MMP-2 or TIMP-1, but did counteract the increase in PSTR and the risk of peritonitis associated with the use of standard PD solutions. This is the first longitudinal study to examine the clinical utility of MMP-2 as a predictor of patient-level outcomes., (Copyright © 2016 International Society for Peritoneal Dialysis.)

Peritoneal dialysis (PD) is a common treatment for patients with reduced or absent renal function. Long-term PD leads to peritoneal injury with structural changes and functional decline. At worst, peritoneal injury leads to encapsulating peritoneal sclerosis (EPS), which is a serious complication of PD. In order to carry out PD safely, it is important to define the mechanism of progression of peritoneal injury and EPS. We prepared rat models of peritoneal injury by intraperitoneal administration of glucose degradation products, such as methylglyoxal (MGO) or formaldehyde (FA), chlorhexidine gluconate (CG), and talc. In rats treated with MGO, peritoneal fibrous thickening with the appearance of basophilic spindle cells with podoplanin, cytokeratin, and α-smooth muscle actin at the surface of the peritoneum was observed. These cells may have been derived from mesothelial cells by epithelial-to-mesenchymal transition. In FA- or CG-treated rats, the peritoneum was thickened, and mesothelial cells were absent at the surface of the peritoneum. The CG- or MGO-treated rats presented with a so-called abdominal cocoon. In the talc-treated rats, extensive peritoneal adhesion and peritoneal thickening were observed. MGO-induced peritoneal injury model may reflect human histopathology and be suitable to analyze the mechanism of progression of peritoneal injury and EPS.

A rise in osmotic concentration (osmolarity) activates the transcription factor Nuclear Factor of Activated T Cells 5 (NFAT5, also known as Tonicity-responsive Enhancer Binding Protein, TonEBP). This is part of a regulatory mechanism of cells adjusting to environments of high osmolarity. Under physiological conditions these are particularly important in the kidney. Activation of NFAT5 results in the modulation of various genes including some which promote inflammation. The osmolarity increases in patients with renal failure. Additionally, in peritoneal dialysis the cells of the peritoneal cavity are repeatedly exposed to a rise and fall in osmotic concentrations. Here we review the current information about NFAT5 activation in uremic patients and patients on peritoneal dialysis. We suggest that high osmolarity promotes injury in the "uremic" milieu, which results in inflammation locally in the peritoneal membrane, but most likely also in the systemic circulation.

Peritoneal dialysis (PD) is a form of renal replacement therapy whose repeated use can alter dialytic function through induction of epithelial-mesenchymal transition (EMT) and fibrosis, eventually leading to PD discontinuation. The peritoneum from Cav1-/- mice showed increased EMT, thickness, and fibrosis. Exposure of Cav1-/- mice to PD fluids further increased peritoneal membrane thickness, altered permeability, and increased the number of FSP-1/cytokeratin-positive cells invading the sub-mesothelial stroma. High-throughput quantitative proteomics revealed increased abundance of collagens, FN, and laminin, as well as proteins related to TGF-β activity in matrices derived from Cav1-/- cells. Lack of Cav1 was associated with hyperactivation of a MEK-ERK1/2-Snail-1 pathway that regulated the Smad2-3/Smad1-5-8 balance. Pharmacological blockade of MEK rescued E-cadherin and ZO-1 inter-cellular junction localization, reduced fibrosis, and restored peritoneal function in Cav1-/- mice. Moreover, treatment of human PD-patient-derived MCs with drugs increasing Cav1 levels, as well as ectopic Cav1 expression, induced re-acquisition of epithelial features. This study demonstrates a pivotal role of Cav1 in the balance of epithelial versus mesenchymal state and suggests targets for the prevention of fibrosis during PD., (© 2014 The Authors. Published under the terms of the CC BY 4.0 license.)

The research study was carried out on 30 white Wistar rats, which were divided into three groups. In the first group the effect of carboxyperitoneum on visceral peritoneum during a two hour period at a pressure of 9-10 mm Hg and after 20 minutes its further fractional replacement during 10 seconds was examined. In the second group, the study was carried out after modeling 12-hours acute adhesive intestinal obstruction. To the third group at the beginning was given a single injection of four component mixture (carboxyperitoneum gel carboxymetiltcellulose novocaine and antibiotic) into the abdominal cavity. In the first group under the condition of tension carboxyperitoneum after a day of use there were signs of desiccations of visceral peritoneum. The increase of lipid peroxidation products and decrease of antioxidant enzymes were also observed. In the second group of animals these processes were exacerbated by acute adhesive intestinal obstruction. In the third group intraabdominal use of four component disperse mixture reduced the negative organic and functional changes in visceral peritoneum and improved its protective properties.

Unlabelled: BACKGROUND, OBJECTIVES AND METHODS: Increased intraperitoneal volume (IIPV) can occur during automated peritoneal dialysis (APD). The contribution of factors such as cycler programming and patient/user actions to IIPV has not been previously explored. The relationship between IIPV and cycler programming, patient/user actions, and ultrafiltration over a two-year period was investigated using US data from Baxter cyclers. Drain/fill volume ratios of > 1.6 to ≤ 2.0 and > 2.0 were defined as Level I and Level II IIPV events, respectively., Results: Level I IIPV events occurred in 2.39% of standard and 4.73% of small fill volume therapies, while Level II IIPV events occurred in 0.26% and 1.33% of therapies, respectively. IIPV events occurred significantly more often in association with tidal peritoneal dialysis (PD) compared to non-tidal PD therapies. In tidal therapies, IIPV events were primarily related to suboptimal programming of total ultrafiltration volume. Factors that increased the odds of IIPV events during standard therapies included programming the initial drain volume target to < 70% of the last fill, and setting minimum drain volumes to < 85% of the fill volume. Bypass of initial drain by patients/users was also associated with a significant increase in the odds of IIPV events in non-tidal, but not tidal PD. An increase in the odds for IIPV was also seen for standard therapies within the highest (> 1,245 mL) versus the lowest (< 427 mL) quartile of ultrafiltration. Similar trends were seen in small fill volume therapies. Clinical presentations associated with IIPV events were not assessed., Conclusions: IIPV events are more frequent in tidal and small fill volume therapies. The greatest potential for IIPV occurred when the total ultrafiltration was set too low for the patient's UF requirements during tidal therapy. Patient/user bypass of drains without reaching the target drain volume contributes significantly to IIPV events in non-tidal PD therapies. Poorly functioning PD catheters may be central to the cycler programming and patient/user actions that lead to IIPV., (Copyright © 2014 International Society for Peritoneal Dialysis.)

Endometriosis (EM) is an oestrogen-dependent disease affecting 10-15 % of women during reproductive age. It is characterised by the presence of endometrial glands, stromal- and smooth muscle-like cells outside of the uterine cavity. Fifty to sixty per cent of women and teenage girls with pelvic pain suffer from EM. EM causes disability and compromises the quality of life in women and young girls significantly. Pain generation in EM is an intricate interplay of several factors such as the endometriotic lesions themselves and the pain-mediating substances, nerve fibres and cytokine-releasing immune cells such as macrophages. These interactions seem to induce a neurogenic inflammatory process. Recently published data demonstrated an increased peptidergic and decreased noradrenergic nerve fibre density in peritoneal lesions. These data could be substantiated by in vitro analyses demonstrating that the peritoneal fluids of patients suffering from EM induced an enhanced sprouting of sensory neurites from chicken dorsal root ganglia and decreased neurite outgrowth from sympathetic ganglia. These findings might be directly involved in the perpetuation of inflammation and pain. Furthermore, the evidence of EM-associated smooth muscle-like cells seems another important factor in pain generation. The peritoneal endometriotic lesion leads to reactions in the surrounding tissue and, therefore, is larger than generally believed. The identification of EM-associated nerve fibres and smooth muscle-like cells fuel discussions on the mechanisms of pain generation in EM, and may present new targets for innovative treatments.

Background: Fluid overload probably contributes to the cardiovascular risk of peritoneal dialysis (PD) patients. We studied the relationship between over-hydration as determined by bioimpedance spectroscopy and dialysis adequacy, nutritional status, and arterial stiffness in Chinese PD patients., Methods: We studied 122 asymptomatic prevalent PD patients: bioimpedance spectroscopy, arterial pulse wave velocity, dialysis adequacy and nutritional status were determined., Results: Of the 122 patients, 88 (72.1%) had over-hydration of ≥ 1 L, while 25 (20.5%) were ≥ 5 L. Over-hydration significantly correlated with total body water (r = 0.474, p < 0.001) and extracellular water (r = 0.755, p < 0.001). Over-hydration was more severe in male and diabetic patients, and significantly correlated with Charlson's comorbidity score, blood pressure, body mass index, body weight, peritoneal transport characteristics, and carotid-femoral pulse wave velocity. Over-hydration significantly correlated with Kt/V (r = -0.287, p = 0.016), serum albumin level (r = -0.465, p < 0.001) and malnutrition inflammation score (r = 0.410, p = 0.006), but not residual renal function., Conclusion: Over-hydration is common in asymptomatic Chinese PD patients. The degree of over-hydration is particularly pronounced in patients who are inadequately dialyzed, have multiple comorbid conditions and low serum albumin levels. Over-hydration is associated with high blood pressure and arterial stiffness, and may contribute to the excessive risk of cardiovascular disease in this group of patients., (Copyright © 2014 International Society for Peritoneal Dialysis.)

Background: Icodextrin induces ultrafiltration (UF) during long-dwell exchanges by creating a difference in oncotic pressure between the peritoneal cavity and plasma; however, the mechanisms governing intra-patient and inter-patient variability in UF when icodextrin is used remain largely unexplained. In the present study, we show theoretically that differences in peritoneal residual volume (VR) have a more profound effect on UF with icodextrin use than with glucose use. This phenomenon is attributed to a differential effect of VR on oncotic, rather than osmotic, pressure between the peritoneal cavity and plasma. ♢, Methods: The three-pore model was used to calculate the effect on UF of VR between 150 mL and 1200 mL when 7.5% icodextrin (ICO) or 3.86% glucose solution is used at the end of a 12-hour dwell in the four patient transport groups (that is, fast to slow). Oncotic (with ICO) and osmotic (with glucose) pressure differences averaged over the entire dwell were also calculated. ♢, Results: As expected, at a nominal VR of 300 mL, UF with glucose differed substantially between the four patient transport groups (2 - 804 mL), whereas UF with ICO did not (556 - 573 mL). When VR was increased to 1200 mL from 150 mL, the concentrations of the oncotic and osmotic agents at the start of the dwell with an infusion volume of 2 L decreased to 4.9% from 7.0% with ICO and to 2.5% from 3.6% with glucose. The decrease in UF on average was greater with ICO [to 252 mL from 624 mL: that is, a reduction of 372 mL (60%)] than with glucose [to 292 mL from 398 mL: that is, a reduction of 106 mL (27%)]. Those trends agreed with the calculated reductions in the oncotic pressure difference with ICO [reduction of 12 mmHg (49%)] and the osmotic pressure difference with glucose [reduction of 19 mmHg (33%)]. ♢, Conclusions: When ICO is used, VR modifies the oncotic pressure difference between the peritoneal cavity and plasma to substantially alter UF. This modification suggests that potential causes of increased VR should be considered when UF with ICO is considerably less than expected. Prospective clinical studies evaluating the relationship between VR and UF with ICO are warranted to validate the theoretical predictions in this report.

BACKGROUND Endometriosis affects 6-10% of women of reproductive age and is associated with chronic pelvic pain, dysmenorrhoea, dyspareunia and infertility. Endometriosis is defined by the presence of endometrial tissue outside the uterus, most commonly attached to the pelvic peritoneum. The endometrium in women with endometriosis is reported to be altered and there is increasing evidence that the phenotype of the pelvic peritoneum may also play a role in the establishment and maintenance of the disease. The aim of this review is to discuss the putative role of the pelvic peritoneum in the pathophysiology of peritoneal endometriosis. METHODS A review was undertaken of the published literature on (i) the anatomy and physiology of the peritoneum and (ii) the potential roles played by peritoneal cells in the establishment and maintenance of peritoneal endometriosis. The current understanding of the biology of peritoneal endometriosis is summarized and the potential interaction of the peritoneum with ectopic endometrial cells in endometriosis is highlighted. RESULTS Several studies indicate that differential expression of peritoneal mesothelial adhesion factors occurs in women with endometriosis, providing potential ectopic endometrial cell attachment sites for the establishment of endometriosis lesions. Changes in the peritoneal mesothelial cell phenotype, including loss of tight junctions, may allow ectopic cells to bind to, or early lesions to invade into, the extracellular matrix. Epithelial-to-mesenchymal transition of peritoneal mesothelial cells may also lead to an increase in lesion invasion and formation of fibrotic tissue in and around the lesion. There is evidence that the peritoneal mesothelium may also play a role in the invasion potential of ectopic cells by production of MMPs increasing local tissue remodelling. Peritoneal immune scavenging function may be lowered in women with endometriosis; for example there is a notable increase in macrophage-derived secretion products in women with endometriosis associated with increases in cell proliferation, cell adhesion and neovascularization. CONCLUSIONS The pelvic peritoneum appears to play a key role in the development and maintenance of endometriosis.

In peritoneal dialysis (PD) patients, the frequent exposure to "unphysiological" dialysis fluids elicits a chronic state of a low-grade peritoneal inflammation leading to interstitial matrix remodeling and angiogenesis. Proinflammatory cytokines are important regulators involved in this inflammatory process that ultimately leads to dysfunction of the peritoneum as a dialysis membrane. We aimed to measure the local concentrations of proinflammatory cytokines in the peritoneal interstitial fluid (IF). Furthermore, we wanted to assess how the driving forces for fluid and solute exchanges are affected in a remodeled interstitial matrix and thus measured the colloid osmotic pressure (COP) gradient in rats that were exposed to chronic PD. After 8 wk of peritoneal dialysis, IF from peritoneum was isolated using a centrifugation method, and was analyzed for cytokine content and COP along with plasma. For several of the proinflammatory cytokines there were gradients from IF to plasma, showing local production. For some cytokines, the concentration in IF was increased severalfold, whereas IL-18 was increased systemically due to PD. Furthermore, the presence of the catheter per se seemed to increase cytokine levels. COP in IF was significantly decreased in the PD group, while collagen and hyaluronan content was increased. Collectively, our data suggest that the increased levels of proinflammatory cytokines after PD may be an integral component of the development of fibrosis and angiogenesis commonly seen in PD patients, and the decreased COP in IF after chronic PD may shift the Starling equilibrium across peritoneal capillaries to an absorptive state.

High mobility group box 1 (HMGB1), a DNA-binding nuclear protein, has been implicated as an endogenous danger signal in the pathogenesis of infection diseases. However, the potential role and source of HMGB1 in the peritoneal dialysis (PD) effluence of patients with peritonitis are unknown. First, to evaluate HMDB1 levels in peritoneal dialysis effluence (PDE), a total of 61 PD patients were enrolled in this study, including 42 patients with peritonitis and 19 without peritonitis. Demographic characteristics, symptoms, physical examination findings and laboratory parameters were recorded. HMGB1 levels in PDE were determined by Western blot and ELISA. The concentrations of TNF-α and IL-6 in PDE were quantified by ELISA. By animal model, inhibition of HMGB1 with glycyrrhizin was performed to determine the effects of HMGB1 in LPS-induced mice peritonitis. In vitro, a human peritoneal mesothelial cell line (HMrSV5) was stimulated with lipopolysaccharide (LPS), HMGB1 extracellular content in the culture media and intracellular distribution in various cellular fractions were analyzed by Western blot or immunofluorescence. The results showed that the levels of HMGB1 in PDE were higher in patients with peritonitis than those in controls, and gradually declined during the period of effective antibiotic treatments. Furthermore, the levels of HMGB1 in PDE were positively correlated with white blood cells (WBCs) count, TNF-α and IL-6 levels. However, pretreatment with glycyrrhizin attenuated LPS-induced acute peritoneal inflammation and dysfunction in mice. In cultured HMrSV5 cells, LPS actively induced HMGB1 nuclear-cytoplasmic translocation and release in a time and dose-dependent fashion. Moreover, cytosolic HMGB1 was located in lysosomes and secreted via a lysosome-mediated secretory pathway following LPS stimulation. Our study demonstrates that elevated HMGB1 levels in PDE during PD-related peritonitis, at least partially, from peritoneal mesothelial cells, which may be involved in the process of PD-related peritonitis and play a critical role in acute peritoneal dysfunction.

Serum concentrations of CA-125 are rarely elevated beyond 1000 U/ml in benign conditions of the ovary in postmenopausal women. In this report, the authors present an unusual case of a 78-year-old woman with an extremely elevated CA-125 concentration of 2897 U/ml without the presence of a malignancy, ascites or pleural effusion. Imaging revealed a large intra-abdominal cystic mass with irregular solid deviations on CT scan, most likely arising from an ovary. Exploratory laparotomy was performed with suspicion of ovarian cancer but histopathological analysis revealed benign serous cystic adenofibroma. This case report highlights the diagnostic challenge of extremely increased levels of CA-125 in postmenopausal women. A possible explanation for this CA-125 elevation could be the mechanical stretch of the peritoneum.

Background: Progressive peritoneal membrane injury and dysfunction are feared repercussions of peritoneal dialysis (PD), and may compromise the long-term feasibility of this therapy. Different strategies have been attempted to prevent or reverse this complication with limited success., Methods: We performed a randomized, open multi-centre trial, aimed at scrutinizing the efficacy of self-administered intraperitoneal (i.p.) bemiparin (BM) to modulate peritoneal membrane dysfunction. The main outcome variables were peritoneal creatinine transport and the ultrafiltration (UF) capacity, estimated during consecutive peritoneal equilibration tests. The trial included a control group who did not undergo intervention. The treatment phase lasted 16 weeks with a post-study follow-up of 8 weeks., Results: Intraperitoneal BM did not significantly improve creatinine transport or the UF capacity, when the whole group was considered. However, we observed a time-limited improvement in the UF capacity for the subgroup of patients with overt UF failure, which was not observed in the control group. Intraperitoneal injection of BM did not carry an increased risk of peritoneal infection or major haemorrhagic complications., Conclusions: Our data do not support the systematic use of BM for management of peritoneal membrane dysfunction in PD patients. Further studies on the usefulness of this approach in patients with overt UF failure are warranted. Intraperitoneal administration of BM is safe in PD patients, provided regulated procedures are respected.

Background: Oxidative stress has been implicated in the development of peritoneal damage. The aim of this study was to evaluate the effects of N-acetylcysteine (NAC) in a rat peritoneal infusion model., Methods: Eighteen male Wistar rats were divided in 3 groups: (i) control group; (ii) HDS group, receiving peritoneal dialysis solution (PDS); and (iii) HDS+NAC group, receiving PDS and oral NAC. Six weeks later they were evaluated for dialysate to plasma urea ratio (D/P), ratio of glucose concentration in peritoneal fluid (G1/G0), thiobarbituric acid reactive substances in plasma and urine and histology of peritoneal membrane., Results: The HDS+NAC group presented a lower increase in solute transport (D/P 0.51 ± 0.1, and G1/GO 0.35 ± 0.06) in comparison with the HDS group (D/P 0.67 ± 0.1; p=0.03, and G1/G0 0.27 ± 0.07; p=0.01). The HDS+NAC group showed lower thiobarbituric acid reactive substance concentrations compared with the HDS group. In the treated group, the peritoneal membrane presented lower thickness., Conclusions: Functional and histological peritoneal changes were significantly reduced by the treatment with NAC.

For patients on peritoneal dialysis (PD), the development of peritonitis, the decline of residual kidney function, and the loss of peritoneal membrane function are central events that affect both patient and technique survival. The use of glucose as the osmotic agent in conventional PD solutions may increase the susceptibility to each of these events. However, its use may also be associated with systemic metabolic perturbations and, in turn, an increase in cardiovascular morbidity. Both in vitro and in vivo evidence suggest that both the local peritoneal and systemic toxicity induced by the use of glucose may be in part mediated by the presence of glucose degradation products (GDPs) coupled with the hyperosmolarity, reduced pH, and use of lactate as the buffer in conventional PD solutions. Therefore, the use of neutral pH, low-GDP (NpHL(GDP)), bicarbonate-buffered PD solutions may represent a promising strategy to attenuate some of these adverse effects. However, the impact of these novel solutions on clinical outcomes remains largely unknown. In this review, we will highlight evidence regarding the biocompatibility of NpHL(GDP) PD solutions, review the utility of current biomarkers in the evaluation of biocompatibility, and discuss the clinical outcome data with these solutions., (© 2011 International Society of Nephrology)

Peritoneal fibrosis (PF) is a recognized complication of long-term peritoneal dialysis (PD) and can lead to ultrafiltration failure. The present study was designed to investigate the protective effects of valsartan on chlorhexidine digluconate-induced PF by decreasing TGF-β1 production in rats. PF was induced in Sprague-Dawley rats by daily administration of 0.5 ml 0.1% chlorhexidine digluconate in normal saline via peritoneal dialysis (PD) tube for 1 week. Rats received daily intravenous injections of low dose valsartan (1 mg/kg) or high dose valsartan (3 mg/kg) for 1 week. After 7 days, conventional 4.25% Dianeal (30 ml) was administered via a PD catheter with a dwell time of 4 h and assessed of peritoneal function. At the end of dialysis, rats were sacrificed and the liver peritoneum was harvested for microscopically and immunohistochemistry. There was no significant difference in mean arterial pressure and heart rate between groups. After 4 h of PD, the D₄/P(4Urea) level was reduced, the D₄/D₀ glucose level, serum and dialysate transforming growth factor-β1 (TGF-β1) level was increased, the liver peritoneum was markedly thicker, and the expression of TGF-β1, alpha-smooth muscle actin (α-SMA), fibronectin, collagen, and vascular endothelial growth factor (VEGF) were elevated in the PF group compared with the vehicle group. High dose of valsartan decreased the serum and dialysate TGF-β1 level, decreased the thickness of the liver peritoneum, and decreased the expression of TGF-β1, α-SMA, fibronectin, collagen, and VEGF-positive cells in liver peritoneum. The low dose of valsartan did not protect against chlorhexidine digluconate-induced PF in rat. Valsartan protected against chlorhexidine digluconate-induced PF in rats by decreasing TGF-β1 production., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

During peritoneal dialysis (PD), constant exposure of mesothelial cells to bioincompatible PD solutions results in the denudation of the mesothelial monolayer and impairment of mesothelial cell function. Hyaluronan, a major component of extracellular matrices, is synthesized by mesothelial cells and contributes to remesothelialization, maintenance of cell phenotype, and tissue remodeling and provides structural support to the peritoneal membrane. Chronic peritoneal inflammation is observed in long-term PD patients and is associated with increased hyaluronan synthesis. During inflammation, depolymerization of hyaluronan may occur with the generation of hyaluronan fragments. In contrast to native hyaluronan which offers a protective role to the peritoneum, hyaluronan fragments exacerbate inflammatory and fibrotic processes and therefore assist in the destruction of the tissue. This paper will discuss the contribution of mesothelial cells to peritoneal membrane alterations that are induced by PD and the putative role of hyaluronan in these processes.

Encapsulating peritoneal sclerosis (EPS) is a serious condition whose frequency is increasing the longer the duration of peritoneal dialysis. To identify prognostic indicators of EPS, we studied here longitudinal changes in peritoneal membrane function of patients who later developed this complication. We identified all patients with an unequivocal diagnosis of EPS who began their peritoneal dialysis in our unit over a 20-year period and matched each of them for dialysis duration and age with four control patients who completed their dialysis. The dialysate/plasma creatinine ratio increased with time in both groups but was significantly higher in the patients with EPS only at the time their dialysis was discontinued. The ultrafiltration capacity was significantly worse for at least 2 years before stopping dialysis, diverging further at the time dialysis ceased, suggesting reduced osmotic conductance in the EPS patients. Both the glucose exposure rate for the 5 years preceding stoppage of dialysis and exposure to the osmotic agent icodextrin were significantly higher. Residual renal function was less in the EPS group, but there was no significant difference in the rates of peritonitis compared to the control group. The 24 h peritoneal protein clearance was not significantly different in EPS patients, possibly due to a greater fibrous matrix. Thus, our study shows that regular peritoneal membrane function tests can identify most patients at high risk of developing EPS before its occurrence.

The development of peritoneal dialysis (PD) as a successful therapy has and still depends on experimental models to test and understand critical pieces of pathophysiology. To date, the majority of studies performed in rat and rabbit models derive mechanistic insights primarily on the basis of interventional pharmacologic agents, blocking antibodies, or transient expression systems. Because body size no longer limits the performance of in vivo studies of PD, genetic mouse models are increasingly available to investigate the molecular and pathophysiologic mechanisms of the peritoneal membrane. We illustrate in this review how these investigations are catching up with other areas of biomedical research and provide direct evidence for understanding transport and ultrafiltration, responses to infection, and structural changes including fibrosis and angiogenesis. These studies are relevant to mechanisms responsible not only for the major complications of PD but also for endothelial biology, host defense, inflammation, and tissue repair processes.

Background: Automated peritoneal dialysis (APD) is widely recommended for the management of high transporters by the International Society of Peritoneal Dialysis (ISPD), although there have been no adequate studies to date comparing the outcomes of APD and continuous ambulatory peritoneal dialysis (CAPD) in this high risk group., Methods: The relative impact of APD versus CAPD on patient and technique survival rates was examined by both intention-to-treat (PD modality at Day 90) and 'as-treated' time-varying Cox proportional hazards model analyses in all patients who started PD in Australia or New Zealand between 1 April 1999 and 31 March 2004 and who had baseline peritoneal equilibration tests confirming the presence of high peritoneal transport status., Results: During the study period, 4128 patients commenced PD. Of these, 628 patients were high transporters on PD at Day 90 (486 on APD and 142 on CAPD). Compared to high transporters treated with CAPD, APD-treated high transporters were more likely to be younger and Caucasian, and less likely to be diabetic. On multivariate intention-to-treat analysis, APD treatment was associated with superior survival [adjusted hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.35-0.87] and comparable death-censored technique survival (HR 0.88, 95% CI 0.64-1.21). Superior survival of high transporters treated with APD versus CAPD was also confirmed in supplemental as-treated analysis (HR 0.72, 95% CI 0.54-0.96), matched case-control analysis (HR 0.60, 95% CI 0.36-0.96) and subgroup analysis of high transporters treated entirely with APD versus those treated entirely with CAPD (HR 0.29, 95% CI 0.14-0.60). There were no statistically significant differences in patient survival or death-censored technique survival between APD and CAPD for any other transport group, except for low transporters, who experienced a higher mortality rate on APD compared with CAPD (HR 2.19, 95% CI 1.02-4.70)., Conclusions: APD treatment is associated with a significant survival advantage in high transporters compared with CAPD. However, APD treatment is associated with inferior survival in low transporters.

Background: The association between peritoneal solute transport rates (PSTRs) and inflammatory markers in patients on peritoneal dialysis (PD) is still under investigation. We aimed to elucidate their relationship during the first year on PD., Methods: We performed a prospective observational study with 187 incident PD patients who were treated with either biocompatible solution (BCS) or conventional solution (CS). Peritoneal dialysate effluent (PDE) and blood samples for the markers and the calculation of mass transfer area coefficient of creatinine (MTAC) were performed at 1, 6 and 12 months after commencing PD., Results: Of the 187 enrolled patients, 110 completed a 1-year study protocol. All PDE markers [interleukin-6 (IL-6), transforming growth factor-beta (TGF-beta), TGF-beta-induced gene-h3 (beta ig-h3), vascular endothelial growth factor (VEGF)] except CA125 increased over time, whereas PSTRs, high-sensitivity C-reactive protein (hs-CRP) and serum IL-6 levels did not change. Serum albumin and log PDE appearance rates (ARs) of IL-6, TGF-beta and CA125 predicted MTAC. The Delta value (12-month minus 1-month) of PDE AR of IL-6 was correlated with those of all other PDE markers. Both 12-month IL-6 and Delta IL-6 ARs in PDE were highest in the upper Delta MTAC tertile. PSTRs in the CS group, unlike BCS, had a tendency to increase over time, demonstrating a time-by-group interaction. Solution type and MTAC were not associated with patient and technique survival., Conclusions: The change in PSTR during the first year of PD is related to PDE IL-6 AR, which may represent intraperitoneal inflammation; however, there does not seem to be a close association between PSTR and the degree of systemic inflammation.

Peritoneal fibrosis, a major complication of peritoneal dialysis, limits the effectiveness of peritoneal dialysis as a treatment of end-stage renal disease. Preventing this complication by identifying targets for therapy has recently received much attention. In the present study, we showed that Notch signaling was highly activated in rats in peritoneal dialysis fluid-induced fibrotic peritoneum, as indicated by increased expression of Jagged-1, Notch-1, and HES-1. Blocking Notch signaling activation by intraperitoneal injection of a gamma-secretase inhibitor, DAPT, significantly attenuated peritoneal fibrosis as indicated by the decreased expression of alpha-smooth muscle actin, collagen I, and vascular endothelial growth factor as well as increased expression of E-cadherin. Moreover, compared with control rats, DAPT-treated rats had a thinner peritoneum with less extracellular matrix accumulation, a lower mass transfer of glucose, and a higher ultrafiltration rate. In addition, transforming growth factor (TGF)-beta1 induced Notch signaling activation in primary rat peritoneal mesothelial cells. DAPT blocked this TGF-beta1-induced Notch signaling activation and therefore significantly inhibited TGF-beta1-induced expression of alpha-smooth muscle actin, collagen I, and vascular endothelial growth factor. Thus, a gamma-secretase inhibitor that interferes with Notch signaling prevents biochemical, histological, and functional consequences of peritoneal fibrosis through inhibiting epithelial to mesenchymal transition of rat peritoneal mesothelial cells. These results support the use of gamma-secretase inhibitors as a novel therapeutic approach for peritoneal fibrosis.

Background: Patients on peritoneal dialysis (PD) with high small solute peritoneal membrane transport have an increased risk of morbidity and mortality. The membrane transport is currently assessed by peritoneal equilibration test (PET), usually performed after the first month of PD because of the early increase of membrane transport after the start of PD. The aim of this study was the assessment of small solute peritoneal membrane transport before and after the start of PD., Methods: The small solute peritoneal membrane transport was evaluated in 34 patients before the start of PD. Twenty-two patients were treated with continuous ambulatory peritoneal dialysis (CAPD) and 12 with automated peritoneal dialysis (APD)., Results: Four months after the start of PD, the small solute peritoneal membrane transport increased only in CAPD patients (D/P(Creat), the ratio between dialysate solute concentration at the end of the PET and creatinine plasma concentration, changed from 0.66 +/- 0.12 to 0.73 +/- 0.07 in CAPD patients and from 0.64 +/- 0.12 to 0.61 +/- 0.07 in APD patients), and after about 16 months of PD, the peritoneal membrane transport was higher in CAPD patients (D/P(Creat) = 0.74 +/- 0.06) than in APD patients (D/P(Creat) = 0.63 +/- 0.10)., Conclusions: Performing the PET before and after the start of PD could provide relevant information about the characteristics of small solute peritoneal membrane transport and could be useful to evaluate the influence of PD modality on the changes in peritoneal membrane transport.

Spiegelian hernias account for less than 1% of all hernias diagnosed in the adult population. The most important factors in the proper diagnostic process are detailed physical examination combined with imaging procedures. Two cases of Spiegelian hernias are presented. The anatomical background of the pathology, as well as diagnostic procedures and surgical treatment, is discussed.

During peritoneal dialysis (PD), exposure of the peritoneal membrane to nonphysiologic solutions causes inflammation, ultimately leading to altered structure and function. Myofibroblasts, one of the cell types that contribute to dysfunction of the peritoneal membrane, can originate from mesothelial cells (MCs) by epithelial-to-mesenchymal transition (EMT), a process that has been associated with an increased rate of peritoneal transport. Because cyclooxygenase-2 (COX-2) is induced by inflammation, we studied the role of COX-2 in the deterioration of the peritoneal membrane. We observed that nonepithelioid MCs found in peritoneal effluent expressed higher levels of COX-2 than epithelioid MCs. The mass transfer coefficient for creatinine correlated with MC phenotype and with COX-2 levels. Although COX-2 was upregulated during EMT of MCs in vitro, COX-2 inhibition did not prevent EMT. In a mouse model of PD, however, COX-2 inhibition with Celecoxib resulted in reduced fibrosis and in partial recovery of ultrafiltration, outcomes that were associated with a reduction of inflammatory cells. Furthermore, PD fluid with a low content of glucose degradation products did not induce EMT or COX-2; the peritoneal membranes of mice treated with this fluid showed less worsening than mice exposed to standard fluid. In conclusion, upregulation of COX-2 during EMT may mediate peritoneal inflammation, suggesting COX-2 inhibition as a potential strategy to ameliorate peritoneal deterioration in PD patients.

Background: Morphological changes associated with long-term peritoneal dialysis (PD) include increased vascular surface area due to angiogenesis, submesothelial fibrosis and epithelial mesenchymal transition. Platelet-derived growth factor (PDGF) has been associated with all of these phenomena, and is a prototypical 'response to injury' growth factor., Methods: Rats received an intraperitoneal injection of adenoviral vector expressing PDGF-B. At sacrifice, we analysed the structure and function of the peritoneal membrane. Gene expression in the peritoneal tissue was assessed for changes suggestive of epithelial mesenchymal transition., Results: Over-expression of PDGF in the rat peritoneum led to significant angiogenesis, cellular proliferation and submesothelial thickening. Although PDGF induced expression of transforming growth factor beta, there was a lack of activation of this growth factor, and we believe that this explains the lack of significant collagen accumulation observed by a hydroxyproline assay. Despite evidence of angiogenesis and subsequent increased solute transport, we observed only a transient, non-significant impact on ultrafiltration function. This suggests that increased vascular surface area is necessary, but not sufficient, to produce ultrafiltration dysfunction. There was no evidence of epithelial mesenchymal transition observed either in regulation of associated genes such as Snail or E-Cadherin or in the lack of dual-labelled epithelial and mesenchymal cells on immunofluorescence. Mesothelial cells exposed to PDGF-B demonstrated increased collagen gene expression., Conclusions: PDGF-B induced angiogenesis without fibrosis in the peritoneum. The lack of significant ultrafiltration dysfunction and epithelial mesenchymal transition, as observed in patients on PD, suggests that PDGF-B may play a role, but is not the integral component, in response to peritoneal injury.

Background: Experimental studies showed that inhibition of AII effects attenuates the development of peritoneal membrane fibrosis and neoangiogenesis. The latter leads to an increase of peritoneal solute transport and ultrafiltration failure. The results of a single-centre study showed that use of ACEI/ARB can prevent the increase of small solute transport in long-term PD patients. Our aim was to investigate whether these results would also be present in a larger population and influence patient and technique survival in long-term PD., Methods: We analysed data from 217 long-term CAPD patients, participating in the Netherlands Cooperative Study on Adequacy of Dialysis (NECOSAD). Included patients underwent CAPD therapy for at least 2 years; 120 of them were treated with the ACE/AII inhibitors-ACEI/ARB group. The control group consisted of 87 patients who received none of the above drugs and 10 patients who had them for <25% of their time on PD., Results: A significant difference in the time course of peritoneal transport was found between the two groups. The value of 24-h D/P creatinine was associated with the PD duration (P = 0.01) and its time course was influenced by use of ACEI/ARB (P = 0.05). We found no effect of ACEI/ARB on patient survival, but some benefit was found for the technique survival: in a multivariate model the hazard ratio for the group with the longest use of ACEI/ARB was 0.5 (CI 0.22-1.4), P = 0.19., Conclusions: We conclude that AII inhibition prevents the increase in small solute transport in long-term PD. These drugs may also have some positive influence on PD technique survival.

The pathophysiology of endometriosis remains unclear but involves a complex interaction between ectopic endometrium and host peritoneal tissues. We hypothesized that disruption of this interaction would suppress endometriotic lesion formation. We hoped to delineate the molecular and cellular dialogue between ectopic human endometrium and peritoneal tissues in nude mice as a first step toward testing this hypothesis. Human endometrium was xenografted into nude mice, and the resulting lesions were analyzed using microarrays. A novel technique was developed that unambiguously determined whether RNA transcripts identified via microarray analyses originated from human cells (endometrium) or mouse cells (mesothelium). Four key pathways (ubiquitin/proteasome, inflammation, tissue remodeling/repair, and ras-mediated oncogenesis) were revealed, demonstrating communication between host mesothelial cells and ectopic endometrium. Morphometric analysis of nude mouse lesions confirmed that necrosis, inflammation, healing and repair, and cell proliferation occurred during xenograft development. These processes were entirely consistent with the molecular networks revealed by the microarray data. The transcripts detected in the xenografts overlapped with differentially expressed transcripts in a comparison between paired eutopic and ectopic endometria from human endometriotic patients. For the first time, components of the interaction between ectopic endometrium and peritoneal stromal tissues are revealed. Targeted disruption of this dialogue is likely to inhibit endometriotic tissue formation and may prove to be an effective therapeutic strategy for endometriosis.

Since the widespread introduction of peritoneal dialysis (PD) into the standard care of patients with chronic kidney disease there has been a shift from the initial focus on technique survival to refinement of the therapy to enhance biocompatibility and improve both the local peritoneal and systemic consequences of PD. One of the most significant contributions to these advances has been the development of novel PD solutions. The use of new manufacturing techniques, buffer presentation, and new osmotic alternatives to glucose have allowed potentially improved peritoneal survival (in terms of structure and function) and improved subjective patient experience. Additional benefits have also included, enhanced management of salt and water removal, supported nutritional status and improvement in the systemic metabolic derangements associated with conventional PD treatment, based on glucose-containing lactate-buffered solutions. The selection of suitable targets for modulation of therapy continues to be hampered by our continued relative ignorance of the local and particularly systemic effects of PD compounded by the dearth of quality, outcome-based studies. The aim of this review is to summarize the characteristics of the next generation of PD fluids currently available, and then to evaluate their possible place in treatment by considering the difference in their effects in a series of structural and functional areas potentially relevant to improving patient outcomes.

Ultrafiltration failure (UFF) is a common complication of long-term peritoneal dialysis (PD). Functionally UFF is in most cases characterized by an enhanced peritoneal mass transfer area coefficient for glucose (PS(g)) combined with a largely unchanged peritoneal glucose osmotic conductance (L(p)Ssigma(g)). Morphologically, marked UFF occurs with fibrosis of the submesothelial zone in the peritoneum, combined with vasculopathy and vascular proliferation in deeper tissues. To computer simulate UFF, changes both in the vasculature and in the interstitium have to be taken into account. For that purpose, we used a three-pore membrane/fiber matrix serial barrier model, applying the three-pore model to the capillaries and the fiber-matrix model to the interstitium. The parameters of the three-pore model have been published previously. The interstitial fiber density was set at 0.5% (vol/vol) and the fiber radius (r(f)) at 6 A during control. If the interstitial fiber density was increased from 0.5 to 3%, and r(f) to 7.5 A (cf. collagen) while the capillary surface area was increased by 40% from control, then PS(g) increased from 9.3 to 11.5 ml/min, while the UF coefficient (L(p)S) was largely unchanged. Further increases in vascular surface area combined with further increases in fiber density caused further increments in PS(g), whereas L(p)S remained unchanged. It is concluded that a matrix of fibers coupled in series with a three-pore membrane may be used for simulating the pathophysiological alterations occurring in the peritoneum in UFF, explaining the commonly observed "uncoupling" of small solute transport (PS) from the peritoneal UF coefficient (L(p)S) in this condition.