Search

The fascia of the pancreatic head is referred to as the retropancreatic fascia of Treitz, and that of the body and tail of the pancreas is named the retropancreatic fascia of Toldt. However, the spatial relationship between the nerves, fascia, and the distribution of the fascia on the dorsal side of the pancreas remains unclear. Therefore, this study aimed to explore the distribution of these fasciae and elucidate the spatial relationship between the nerves and arteries connecting the retroperitoneal space and the peritoneal organs by studying eight cadavers using macroscopic anatomical examination, wide-range serial sectioning, and three-dimensional reconstruction. The fasciae of Treitz and Toldt converge caudally to the root of the superior mesenteric artery (SMA), forming a narrower gap around the roots of the celiac trunk and SMA than in the celiac plexus. The fasciae eventually get closer to each other, and the boundary between them becomes obscured, providing coverage to the anterior surface of the aorta between the SMA and the inferior mesenteric artery. The celiac plexus does not penetrate the fascia but converges before spreading into the pancreas. Similarly, the arteries pass through this gap in the fasciae. Our findings suggest that the retroperitoneal space and peritoneal organs are connected through a narrow no-fascia area, with the distribution of the fascia relating to nervous and vascular pathways. Our findings reveal that the distribution of the avascular plane may provide a crucial anatomical foundation for abdominal digestive organ surgery by reducing bleeding volume and determining the dissection region., (© 2024 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

Introduction: The aim of this study was to investigate the expression of aquaporin 1 (AQP-1), AQP-3 and vascular endothelial growth factor A (VEGF-A) in peritoneal tissues of patients without kidney disease, chronic kidney disease at stages 5 (CKD 5) and patients on prolonged peritoneal dialysis with ultrafiltration failure (PDUFF), and elucidate the possible mechanism of peritoneal dialysis ultrafiltration failure., Methods: Peritoneal specimens were collected from the following patient groups at Xianju People's hospital: CKD 5, PD-UFF and normal control groups. Routine staining and immunohistochemical analyses were performed on samples obtained from the three groups., Results: The expression of AQP-1 and AQP-3 on peritoneal mesothelial cells, peritoneal vessels and in the interstitium was significantly lower in the PD-UFF group than the CKD 5 and control groups (P < .01), while no statistically significant difference was found between the CKD 5 and control groups (P > .05). In contrast, VEGF-A expression was significantly higher in peritoneal mesothelial cells, peritoneal vessels and the interstitium in the PD-UFF group than the CKD 5 and control groups (P < .01). No statistically significant difference was found between the CKD 5 and control groups (P > .05)., Conclusion: AQP-1 and AQP-3 expression levels decrease in peritoneal mesothelial cells and the vascular interstitium of patients with a prolonged peritoneal dialysis course, while VEGF-A expression gradually increases. The formation of peritoneal neovascularization and the decrease in AQP expression may be primarily associated with peritoneal dialysis ultrafiltration failure.  DOI: 10.52547/ijkd.6928.

Peritoneal dialysis (PD) is a valuable 'home treatment' option, even more so during the ongoing Coronavirus pandemic. However, the long-term use of PD is limited by unfavourable tissue remodelling in the peritoneal membrane, which is associated with inflammation-induced angiogenesis. This appears to be driven primarily through vascular endothelial growth factor (VEGF), while the involvement of other angiogenic signaling pathways is still poorly understood. Here, we have identified the crucial contribution of mesothelial cell-derived angiogenic CXC chemokine ligand 1 (CXCL1) to peritoneal angiogenesis in PD. CXCL1 expression and peritoneal microvessel density were analysed in biopsies obtained by the International Peritoneal Biobank (NCT01893710 at www.clinicaltrials.gov), comparing 13 children with end-stage kidney disease before initiating PD to 43 children on chronic PD. The angiogenic potential of mesothelial cell-derived CXCL1 was assessed in vitro by measuring endothelial tube formation of human microvascular endothelial cells (HMECs) treated with conditioned medium from human peritoneal mesothelial cells (HPMCs) stimulated to release CXCL1 by treatment with either recombinant IL-17 or PD effluent. We found that the capillary density in the human peritoneum correlated with local CXCL1 expression. Both CXCL1 expression and microvessel density were higher in PD patients than in the age-matched patients prior to initiation of PD. Exposure of HMECs to recombinant CXCL1 or conditioned medium from IL-17-stimulated HPMCs resulted in increased endothelial tube formation, while selective inhibition of mesothelial CXCL1 production by specific antibodies or through silencing of relevant transcription factors abolished the proangiogenic effect of HPMC-conditioned medium. In conclusion, peritoneal mesothelium-derived CXCL1 promotes endothelial tube formation in vitro and associates with peritoneal microvessel density in uremic patients undergoing PD, thus providing novel targets for therapeutic intervention to prolong PD therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Catar, Bartosova, Kawka, Chen, Marinovic, Zhang, Zhao, Wu, Zickler, Stadnik, Karczewski, Kamhieh-Milz, Jörres, Moll, Schmitt and Witowski.)

There has been a significant research interest in nanocrystals as a promising technology for improving the therapeutic efficacy of poorly water-soluble drugs, such as resveratrol. Little is known about the interaction of nanocrystals with biological tissue. The aim of this study was to investigate the potential use of resveratrol (RSV) and its nanocrystals (NANO-RSV) as antitumor agents in Ehrlich ascites tumour (EAT)-bearing mice and the interaction of nanocrystals with biological tissue through biochemical and histological changes of kidney, liver and EAT cells. After intraperitoneal injection of 2.5 × 10 6 cells into the abdominal cavity of mice, treatment of animals was started next day by injecting RSV or NANO-RSV at a dose of either 25 or 50 mg/kg every other day for 14 days. The results show that the administration of resveratrol and its nanocrystals lead to significant reductions in the proliferation of tumour cells in the abdominal cavity, and a reduction of the number of blood vessels in the peritoneum, with low systemic toxicity. In histopathological examinations, greater hepatocellular necrosis and apoptosis, hepatic fibrosis around the central vein and degeneration with minor fatty change were observed with RSV than with NANO-RSV. Inflammation with proximal tubular necrosis and renal glomerulus swelling were also observed, together with slight elevation of several biochemical parameters in both the RSV and NANO-RSV groups. In order to increase the beneficial effects and reduce risks associated with resveratrol nanocrystals, additional factors such as dose, genetic factors, health status, and the nature of the target cells should also be considered., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: During peritoneal dialysis (PD), solute transport and ultrafiltration are mainly achieved by the peritoneal blood vasculature. Glycocalyx lies on the surface of endothelial cells and plays a role in vascular permeability. Low-glucose degradation product (GDP), pH-neutral PD solutions reportedly offer higher biocompatibility and lead to less peritoneal injury. However, the effects on the vasculature have not been clarified., Methods: Peritoneal tissues from 11 patients treated with conventional acidic solutions (acidic group) and 11 patients treated with low-GDP, pH-neutral solutions (neutral group) were examined. Control tissues were acquired from 5 healthy donors of kidney transplants (control group). CD31 and ratio of luminal diameter to vessel diameter (L/V ratio) were evaluated to identify endothelial cells and vasculopathy, respectively. Immunostaining for heparan sulfate (HS) domains and Ulex europaeus agglutinin-1 (UEA-1) binding was performed to assess sulfated glycosaminoglycans and the fucose-containing sugar chain of glycocalyx., Results: Compared with the acidic group, the neutral group showed higher CD31 positivity. L/V ratio was significantly higher in the neutral group, suggesting less progression of vasculopathy. Both HS expression and UEA-1 binding were higher in the neutral group, whereas HS expression was markedly more preserved than UEA-1 binding in the acidic group. In vessels with low L/V ratio, which were found only in the acidic group, HS expression and UEA-1 binding were diminished, suggesting a loss of glycocalyx., Conclusion: Peritoneal endothelial glycocalyx was more preserved in patients treated with low-GDP, pH-neutral solution. The use of low-GDP, pH-neutral solutions could help to protect peritoneal vascular structures and functions., (© 2021. Japanese Society of Nephrology.)

[Figure: see text].

The biological activity of vitamin D, which mediated by the vitamin D receptor, is widespread throughout the body. The present study aimed to define whether 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3) can protect against the progression of peritoneum fibrosis (PF) through its impact on the expression of connective tissue growth factor (CTGF) and heat shock protein 47 (HSP47) in vivo and in vitro. The male Sprague-Dawley (SD) rats of PF were induced by daily intraperitoneally injection of chlorhexidine gluconate (CG) for 4 wks. PF Rats were also treated with calcitriol (i.p. 6 ng/100g*d) from initiation of the CG. In calcitriol rats, the ultrafiltration and the ratio of dialysate urea nitrogen to blood urea nitrogen were improved (P < 0.05), pathological changes and peritoneal thickness were milder than that of the PF group. Calcitriol ameliorated high glucose-induced HSP47 expression in peritoneal mesothelial cells via CTGF down-regulation both at the mRNA level and protein level. Furthermore, calcitriol prevented angiogenic mediators of fibrosis by reduced the expression of CD34 and vascular endothelial growth factor (VEGF). The present study demonstrated that 1,25-(OH)2D3 intervention had a partially protective effect on peritoneum fibrosis, which might inhibit CTGF/HSP47 and CD34/VEGF in the peritoneum tissues., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

The introduction of total mesorectal excision and wider use of laparoscopic surgery pushed the field of colorectal surgery into an era of interfasical dissection. The Japanese suggestion of fascial arrangement of the trunk in a multilaminar, symmetrical and parallel way helps in better understanding of fascial relationship and interfascial planes surrounding the colon and the rectum. However, different interpretations of the multilayer retroperitoneal fascial relationship, complexity of fascial structures within the pelvis and dense adhesion between two apposed fasciae at special points make it still challenging for the surgeon to decide on the precise interfascial plane for colorectal mobilization. Small vessels on fasica propria of the rectum and various retroperitoneal fascia, especially ureterohypogastric fascia show distinctive features. The root of small vessels on fascia propria of the rectum helps to identify the anterolateral and posterolateral interfascial plane in the middle and low rectum. The longitudinal trajectory of small vessel on ureterohypogastric fascia and scarcity interfascial vascular communication between mesocolic and retroperitoneal fascia help the surgeon to find and stay in the interfacial plane during colorectal mobilization. More knowledge of fascial and interfascial plane will certainly help achieve better mesocolic mesorectal integrity and reduce the risk of injuries to autonomic nerves. More anatomical, histological and embryological studies are warranted with respect to relationship between small vessels and fasciae.

Most women with epithelial ovarian cancer (EOC) suffer from peritoneal carcinomatosis upon first clinical presentation. Extensive peritoneal carcinomatosis has a poor prognosis and its pathophysiology is not well understood. Although treatment with systemic intravenous chemotherapy is often initially successful, peritoneal recurrences occur regularly. We hypothesized that insufficient or poorly-perfused microvasculature may impair the therapeutic efficacy of systemic intravenous chemotherapy but may also limit expansive and invasive growth characteristic of peritoneal EOC metastases. In 23 patients with advanced EOC or suspicion thereof, we determined the angioarchitecture and perfusion of the microvasculature in peritoneum and in peritoneal metastases using incident dark field (IDF) imaging. Additionally, we performed immunohistochemical analysis and 3-dimensional (3D) whole tumor imaging using light sheet fluorescence microscopy of IDF-imaged tissue sites. In all metastases, microvasculature was present but the angioarchitecture was chaotic and the vessel density and perfusion of vessels was significantly lower than in unaffected peritoneum. Immunohistochemical analysis showed expression of vascular endothelial growth factor and hypoxia inducible factor 1α, and 3D imaging demonstrated vascular continuity between metastases and the vascular network of the peritoneum beneath the elastic lamina of the peritoneum. We conclude that perfusion of the microvasculature within metastases is limited, which may cause hypoxia, affect the behavior of EOC metastases on the peritoneum and limit the response of EOC metastases to systemic treatment.

Competing Interests: Declaration of competing interest None.

Aim: Studies showed an increased visceral adipose tissue and peritoneal angiogenesis in peritoneal dialysis (PD) patients. However, the relationship between the visceral adipose expands and peritoneal angiogenesis remains unclear., Methods: Pref-1 (preadipocyte factor-1) recombinant adeno-associated virus (AAV) and control AAV were constructed. Mice were divided into four groups, mice in control and PD group were injected intraperitoneally with PBS, mice in control-AAV-PD were injected intraperitoneally with plaque-forming unit (PFU) control AAV and mice in pref-1-AAV-PD group were injected with PFU recombinant AAV. Two weeks later, control group was injected intraperitoneally with normal saline while other groups were injected intraperitoneally with 4.25% peritoneal dialysis fluid (PDF). Thirty days later, viscerall adipose tissue was collected and weighed. Pref-1 protein expression was measured by Western blot, and peritoneal permeability was measured by Evans blue. Cluster of differentiation 31(CD31) immunohistochemical staining was used to detect mesenteric blood vessel number, and vascular endothelial growth factor (VEGF) in serum were measured by enzyme-linked immunosorbent assay., Results: Pref-1 protein expression increased in pref-1-AAV-PD group. Visceral adipose expanded in PD and control-AAV-PD group while decreased in pref-1-AAV-PD group, which approves PD fluid enhance visceral adipogensis, and the process could be inhibited by Pref-1 recombinant AAV. The reduction of peritoneal vessel number and the decrease of vascular permeability as well as down-regulation of serum vascular endothelial growth factor observed in pref-1-AAV-PD group suggested peritoneal angiogenesis could be inhibited following visceral adipose tissue reduction., Conclusion: Visceral adipose expands is associated with peritoneal angiogenesis in PD treatment, and prevention of visceral adipogenesis may be an alternative way to protect the validity of peritoneum. Copyright © 2019 John Wiley & Sons, Ltd., (© 2019 Asian Pacific Society of Nephrology.)

Objective: Experimental assessment of the effect of modified and unmodified surgical suture material on abdominal adhesive process., Material and Methods: The study was performed on male rats of the Wistar subpopulation. There were 5 animals in each group. In all animals, midline abdominal incision was followed by suturing the parietal peritoneum with modified and unmodified suture material. All animals were euthanized with carbon dioxide vapors in 14 days after surgery. Macro- and microscopic assessment of severity of abdominal adhesive process was carried out. Two types of preparation of excised complexes 'peritoneum-suture material-adhesion' were applied for histological examination: paraffin sections and embedding in epoxy resin. Specimens were stained by Van Gieson and with methylene blue solution. Histological specimens were examined using Axio Imager A1 light microscope (Zeiss, Germany)., Results: Polypropylene filaments result extensive adhesions occupying about 75% of the area. Adhesions have a dense structure with signs of vascularization. Modification of suture material with solution of polyhydroxybutyrate/hydroxyvalerate and heparin reduce severity of adhesions. The use of modified suture material was followed by adhesions with more loose structure, no signs of vascularization. Adhesions occupied less than 25% of the area. Histological examination of excised complexes 'peritoneum-suture material-adhesion' revealed accumulation of inflammatory cells around the unmodified suture material, while there were no signs of tissue inflammatory process around the modified sutures., Conclusion: Application of polyhydroxybutyrate/hydroxyvalerate and heparin on the surface of surgical sutures is an effective method for prevention of abdominal adhesions.

Background: Deposition of advanced glycation end products (AGEs) is frequently found in the peritoneum of patients on peritoneal dialysis (PD). Angiogenesis is also observed in the peritoneum. However, the clinical significance of AGEs and angiogenesis in the peritoneum is not fully understood. We evaluated the maturation of capillary vessels and investigated whether AGEs are associated with angiogenesis and peritoneal function in the peritoneal membrane., Methods: Peritoneum obtained when PD catheters were removed from 61 patients with PD was analyzed. The peritoneum was immunohistochemically stained with anti-CD34 (for endothelial cells), anti-alpha smooth muscle actin (αSMA) (for pericytes), and anti-AGE antibodies. We defined CD34-positive and αSMA-negative vessels as immature capillary vessels in peritoneal membranes using serial sections. We evaluated the associations between vessel density, peritoneal function (dialysate-to-plasma ratio for creatinine (D/P creatinine)), and the degree of AGE deposition., Results: AGE accumulation in the interstitium was positively associated with the duration of PD ( p < 0.01). AGE accumulation in the interstitium and vascular wall was positively correlated with the use of acidic solution ( p < 0.05) and the maximum value of D/P creatinine ( p < 0.05). AGE accumulation in the vascular wall was significantly associated with immature capillary density (CD34+/αSMA-) in the peritoneum ( p < 0.01). Vessel density was not significantly correlated with the last measurement of D/P creatinine ( p = 0.126, r = 0.202), However, immature capillary density was positively correlated with the last measurement of D/P creatinine ( p < 0.05, r = 0.278)., Conclusions: AGE accumulation is significantly associated with immature angiogenesis and peritoneal dysfunction in patients undergoing PD.

The artificial pancreas requires fast and reliable glucose measurements. The peritoneal space has shown promising results, and in one of our studies we detected glucose changes in the peritoneal space already at the same time as in the femoral artery. The peritoneal lining is highly vascularised, covered by a single layer of mesothelial cells and therefore easily accessible for proper sensor technology, e.g. optical technology. We hypothesize that the rapid intraperitoneal glucose dynamics observed in our study was possible because the sensors were located directly at the peritoneal lining, at the point where the glucose molecules entered the peritoneal space. Glucose travels slowly in fluids by diffusion, and a longer distance between the sensor and the peritoneal lining would consequently result in slower dynamics. We therefore propose to place the glucose sensor in an artificial pancreas as closely to the peritoneal lining as possible, or even utilize appropriate sensor technology to measure glucose in the peritoneal lining itself., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Formation of peritoneal adhesions is the most frequent complication of abdominal and pelvic surgery and comprises a lifelong risk of adhesion-related morbidity and mortality. Some of the existing antiadhesive barriers are less effective in the presence of blood. In this study, we investigate the efficacy and safety of ultrapure alginate gel in the presence of blood., Methods: In experiment 1 (30 rats), 1 mL ultrapure alginate gel was compared with no intervention in a model of cecal abrasion and persisting peritoneal bleeding by incision of the epigastric artery. In experiment 2 (30 rats), 2 mL ultrapure alginate gel was compared with no intervention in a model where a 1 mL blood clot was instilled intra-abdominally and a cecal resection was performed. The primary endpoint was the incidence and severity of adhesions after 14 d., Results: In experiment 1, seven of 15 rats in the experimental group had intra-abdominal adhesions compared with 13 of 15 rats in the control group (P = 0.05); 3 of 15 rats had adhesions at the site of injury compared with 12 of 15 rats in the control group (P < 0.01). The severity and extent of adhesions was also reduced (P < 0.01). In experiment 2, 12 of 13 rats had adhesions compared with 13 of 14 rats in the control group (P = 1.00)., Conclusions: Ultrapure alginate gel reduces the incidence and severity of adhesion in the presence of persisting bleeding, but not in a model of cecal resection and blood clot., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Liposome supported peritoneal dialysis is a recently described technique which may eventually be applicable in the clinical scenario of the intoxicated patient. We evaluated the hypothesis that intravenous injection of lipid emulsion (ILE) would augment acidic pH gradient liposome supported peritoneal dialysis (LSPD). Orogastrically amitriptyline dosed rats were treated with either Sodium bicarbonate (NaHCO3) intravenously and standard intraperitoneal dialysate (Group A); NaHCO3 intravenously and LSPD (Group B); or ILE and LSPD (Group C). The primary endpoint was dialysate amitriptyline concentration after a 60 min dwell. Secondary analysis included an estimate of extraction ratio for peritoneal blood flow (ERs). There were significantly higher intraperitoneal concentrations of amitriptyline and ERs in the two groups treated with LSPD (Group B, p = 0.02, Group C, p < 0.01 vs. Group A). There was no observed effect for ILE on intraperitoneal amitriptyline concentration or ERs (p > 0.20). LSPD increased the amitriptyline concentration in peritoneal dialysate. No further increase was demonstrated with ILE. This may be either because such an effect is absent, or type II error. Exploratory analysis suggests LSPD may be driven by total rather than free drug concentrations.

Ultrafiltration failure in long-term peritoneal dialysis patients is a well-known and important, but poorly-explained complication of the treatment. Transcapillary ultrafiltration consists mainly of small-pore fluid transport and partly of free-water transport. The former is to a large extent dependent on the hydrostatic pressure gradient and on the number of perfused peritoneal microvessels. Free-water transport depends mainly on the crystalloid osmotic gradient. A longitudinal analysis of peritoneal transport has shown a dramatic decrease of net ultrafiltration and small-pore fluid transport after 4 years of peritoneal dialysis. It will be argued that in contrast to common belief, a decrease of osmotically induced water transport cannot be the major contributor to long-term ultrafiltration failure. By exclusion of potential alternatives, the presence of vasculopathy in the peritoneal microcirculation is the most likely explanation. The resulting narrowing of vascular lumina will decrease the hydrostatic pressure gradient and thereby small-pore fluid transport and net ultrafiltration. Deposition of advanced glycosylation end products in peritoneal vessels may be important in the development of vasculopathy. This hypothesis is supported by morphological and functional results of dialysis with "biocompatible" solutions.
.

Gastrointestinal and peritoneal ischemic disease due to unknown etiology present with intestinal obstruction and/or peritonitis otherwise in healthy patient emerged as fatal disease at Arba Minch General Hospital. This disorder was diagnosed based on intraoperative finding. Clinical presentation and natural history of disease progression were similar. It is estimated that about 6-10 lives are being claimed each year at Arba Minch Hospital with this disease of unidentified cause accounting for the largest figure of surgical department. Here we report case analysis and literature review illustrating clinical presentation, workup, preoperative diagnosis, intraoperative diagnosis, and final outcome of fatal gastrointestinal and peritoneal ischemic disease.

The effect of peritoneal dialysates with low-glucose degradation products on peritoneal membrane morphology is largely unknown, with functional relevancy predominantly derived from experimental studies. To investigate this, we performed automated quantitative histomorphometry and molecular analyses on 256 standardized peritoneal and 172 omental specimens from 56 children with normal renal function, 90 children with end-stage kidney disease at time of catheter insertion, and 82 children undergoing peritoneal dialysis using dialysates with low-glucose degradation products. Follow-up biopsies were obtained from 24 children after a median peritoneal dialysis of 13 months. Prior to dialysis, mild parietal peritoneal inflammation, epithelial-mesenchymal transition and vasculopathy were present. After up to six and 12 months of peritoneal dialysis, blood microvessel density was 110 and 93% higher, endothelial surface area per peritoneal volume 137 and 95% greater, and submesothelial thickness 23 and 58% greater, respectively. Subsequent peritoneal changes were less pronounced. Mesothelial cell coverage was lower and vasculopathy advanced, whereas lymphatic vessel density was unchanged. Morphological changes were accompanied by early fibroblast activation, leukocyte and macrophage infiltration, diffuse podoplanin presence, epithelial mesenchymal transdifferentiation, and by increased proangiogenic and profibrotic cytokine abundance. These transformative changes were confirmed by intraindividual comparisons. Peritoneal microvascular density correlated with peritoneal small-molecular transport function by uni- and multivariate analysis. Thus, in children on peritoneal dialysis neutral pH dialysates containing low-glucose degradation products induce early peritoneal inflammation, fibroblast activation, epithelial-mesenchymal transition and marked angiogenesis, which determines the PD membrane transport function., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Peritonitis is still a major cause of the death in peritoneal dialysis (PD) patients despite the significant decline of the peritonitis rates in recent years. The present study is designed to evaluate the therapeutic potential of peroxisome proliferator-activated receptor-γ agonist, rosiglitazone, on the structure and function of the peritoneum in a PD rat accompanied with peritonitis induced by lipopolysaccharide (LPS). Our data showed that the peritoneal membrane in the LPS-only group showed increased peritoneal thickness, vessel density, and hypercellularity compared with the PD-only group. Rosiglitazone administration significantly inhibited increase of the three indicators in PD rats with LPS treatment. In line with this, rosiglitazone improved function of the peritoneum in LPS-induced PD rats receiving rosiglitazone, which was reflected by decreased D/P urea and D/P albumin. Mechanistically, rosiglitazone-mediated improvements in the damaged structure and function of the peritoneum in PD rats with LPS treatment were associated with reduced inflammation and preserving mesothelial cell monolayer resulted from up-regulation of AQP-1 and ZO-1. Our findings thus suggest that peroxisome proliferator-activated receptor γ (PPAR-γ) activation might be a reasonable strategy to prevent and ameliorate peritoneal deterioration in PD patients, especially with peritonitis., (© 2018 The Author(s).)

The wingless-type mouse mammary tumor virus integration site family (WNT) signaling pathway is involved in wound healing and fibrosis. We evaluated the WNT signaling pathway in peritoneal membrane injury. We assessed WNT1 protein expression in the peritoneal effluents of 54 stable peritoneal dialysis (PD) patients and WNT-related gene expression in ex vivo mesothelial cell cultures from 21 PD patients. In a transforming growth factor-β (TGF-β)-mediated animal model of peritoneal fibrosis, we evaluated regulation of the WNT pathway and the effect of WNT inhibition on peritoneal fibrosis and angiogenesis. WNT1 and WNT2 gene expression were positively correlated with peritoneal membrane solute transport in PD patients. In the mouse peritoneum, TGF-β-induced peritoneal fibrosis was associated with increased expression of WNT2 and WNT4. Peritoneal β-catenin protein was significantly upregulated after infection with adenovirus expressing TGF-β (AdTGF-β) along with elements of the WNT signaling pathway. Treatment with a β-catenin inhibitor (ICG-001) in mice with AdTGF-β-induced peritoneal fibrosis resulted in attenuation of peritoneal angiogenesis and reduced vascular endothelial growth factor. Similar results were also observed with the WNT antagonist Dickkopf-related protein (DKK)-1. In addition to this, DKK-1 blocked epithelial-mesenchymal transition and increased levels of the cell adhesion protein E-cadherin. We provide evidence that WNT signaling is active in the setting of experimental peritoneal fibrosis and WNT1 correlates with patient peritoneal membrane solute transport in PD patients. Intervention in this pathway is a possible therapy for peritoneal membrane injury.

Background: Molecular mechanisms of peritoneal dialysis (PD) ultrafiltration failure, peritoneal neo-angiogenesis, and fibrosis remain to be determined. We aimed to determine the role of heparin-binding EGF-like growth factor (HB-EGF) inhibition on angiogenesis of peritoneal membrane in a PD rat model., Methods: 32 male Wistar rats were assigned into (1) control group; (2) uremic non-PD group: subtotal nephrectomy-induced uremic rats without PD; (3) uremic rats subjected to PD: uremic rats that were dialyzed with Dianeal ® for 4 weeks; (4) CRM 197 group: dialyzed uremic rats were supplemented with CRM197, a specific HB-EGF inhibitor. Peritoneal transport function was examined by peritoneal equilibration test. Expression of HB-EGF and EGFR in peritoneal samples were examined by real-time PCR, immunohistochemical staining, and western blot., Results: Progressive angiogenesis and fibrosis were observed in uremic PD rats, and there were associated with decreased net ultrafiltration (nUF), increased permeability of peritoneal membrane, and reduced expression of HB-EGF and EGFR protein and mRNA in uremic PD rats compared to uremic non-PD or control groups (both p < 0.05). CRM197 significantly induced peritoneal membrane permeability, decreased nUF, increased higher vessel density, and reduced pericyte count compared to that of uremic PD rats. The levels of HB-EGF and EGFR expression negatively correlated with vessel density in peritoneal membrane (both p < 0.001)., Conclusion: PD therapy was associated with peritoneal angiogenesis, functional deterioration, and downregulation of HB-EGF/EGFR. Pharmacological inhibition of HB-EGF promoted PD-induced peritoneal angiogenesis and fibrosis and ultrafiltration decline, suggesting that HB-EGF downregulation contributes to peritoneal functional deterioration in the uremic PD rat model.

Purpose: To compare polyglactin 910 and simple catgut sutures for the incidence of intraperitoneal adhesions., Methods: Twenty female Wistar rats were placed into two groups. Group 1 received ischemic sutures and Group 2 received polyglactin 910. Five sutures inductive of adhesions in each rat were made. After 14 days, the rats were euthanized with an assessment of the presence of adhesions, the number of sutures involved and classification according to the Granat et al. scale described by Ozel et al17., Results: In total, 19 of the 20 rats presented adhesions, with nine from Group 1 and ten from Group 2. There was a smaller number of affected sutures in Group 1, while in Group 2 the majority of the sutures formed adhesions (p=0.0197). According to the Granat et al. scale, Group 1 predominately developed fine, filamentous adhesions or thickening in a restricted area. Group 2 mainly presented extensive, thick adhesions with the involvement of the viscera (p=0.0055)., Conclusion: Polyglactin 910 sutures formed more adhesions that were more extensive and thicker than the simple catgut sutures.

The characteristic features of chronic peritoneal injury with peritoneal dialysis (PD) are submesothelial fibrosis and neoangiogenesis. Transforming growth factor (TGF)β and vascular endothelial growth factor (VEGF)-A are the main mediators of fibrosis and neoangiogenesis, respectively; however, the effect of the interaction between them on the peritoneum is not well known. In this study, we investigated the relationship between TGF-β1 and VEGF-A in inducing peritoneal fibrosis by use of human tissues and dialysate, cultured cells, and animal models. The VEGF-A concentration correlated with the dialysate-to-plasma ratio of creatinine (D/P Cr) ( P < 0.001) and TGF-β1 ( P < 0.001) in human PD effluent. VEGF-A mRNA levels increased significantly in the peritoneal tissues of human ultrafiltration failure (UFF) patients and correlated with number of vessels ( P < 0.01) and peritoneal thickness ( P < 0.001). TGF-β1 increased VEGF-A production in human mesothelial cell lines and fibroblast cell lines, and TGF-β1-induced VEGF-A was suppressed by TGF-β receptor I (TGFβR-I) inhibitor. Incremental peak values of VEGF-A mRNA stimulated by TGF-β1 in human cultured mesothelial cells derived from PD patients with a range of peritoneal membrane functions correlated with D/P Cr ( P < 0.05). To evaluate the regulatory mechanisms of VEGF-A and neoangiogenesis in vivo, we administered TGFβR-I inhibitor intraperitoneally in a rat chlorhexidine-induced peritoneal injury (CG) model. TGFβR-I inhibitor administration in the CG model decreased peritoneal thickness ( P < 0.001), the number of vessels ( P < 0.001), and VEGF-A levels ( P < 0.05). These results suggest that neoangiogenesis is associated with fibrosis through the TGF-β1-VEGF-A pathway in mesothelial cells and fibroblasts. These findings are important when considering the strategy for management of UFF in PD patients.

Epithelial ovarian cancer (EOC) is believed to cause peritoneum dissemination through microenvironmental cell‑to-cell communication between the tumor and mesothelium, leading to the further acquisition of progressive and metastatic potentials. In the present study, we aimed to determine the role of cancer-associated mesothelial cells (CAMCs) in the promotion of tumor neovascularization and vascular permeability via enhanced vascular endothelial growth factor (VEGF) production. We examined whether a characteristic morphological change in human peritoneal mesothelial cells (HPMCs) was observed in the presence of malignant ascites and tumor-derived TGF-β. We focused on the enhanced production of VEGF in CAMCs and its crucial role in endothelial migration and tube formation. Normal HPMCs showed an epithelial morphology with a cobblestone appearance. When HPMCs were co-cultured with malignant ascites from patients with advanced EOC, a dramatic morphologic change was noted from an epithelioid pattern to an α-SMA-positive fibroblastic, mesenchymal pattern. Additionally, we found that EOC-derived TGF-β induced typical EMT-like morphological alteration in HPMCs, which was associated with CAMCs. We further discovered that CAMCs play a crucial role in the enhanced migration and tube formation of endothelial cells by the promotion of VEGF production. In conclusion, our findings indicate the possible involvement of CAMCs in the neovascularization of EOC and enhancement of vascular permeability, resulting in the formation of malignant ascites. The novel mechanism of CAMCs as a facilitator of EOC progression is displayed by microenvironmental cell-to-cell communication between EOC and the mesothelium.

Background/aims: This study describes the peritoneal microcirculation, compares quantitative parameters and angioarchitecture to the standard of sublingual microcirculatory assessment, and determines the practical feasibility of this method., Methods: Incident dark field imaging was performed of the peritoneum and sublingually to determine angioarchitecture, total and perfused vessel density (TVD and PVD), the proportion of perfused vessels (PPV), the microvascular flow index (MFI) and image acquisition time., Results: Peritoneal angioarchitecture was characterized by a quadrangular network of longitudinally oriented capillaries, often flanked by fat cells. Differences between peritoneal and sublingual microcirculation were observed with regard to TVD (peritoneum 12 mm/mm2 [95% CI 10-14] vs. sublingual 23 mm/mm2 [95% CI 21-25]; p < 0.0001), PVD (peritoneum 11 mm/mm2 [95% CI 9-13] vs. sublingual 23 mm/mm2 [95% CI 21-25]; p < 0.0001), PPV (peritoneum 88% [95% CI 79-97] vs. sublingual 99% [95% CI 99-100]; p = 0.014), and MFI (peritoneum 3 [IQR 2.3-3.0] vs. sublingual 3 [IQR 3.0-3.0]; p = 0.012). There was no difference in image acquisition time (peritoneum 2: 34 min [95% CI 1: 49-3: 19] vs. sublingual 2: 38 [95% CI 1: 37-3: 32]; p = 0.916)., Conclusion: The peritoneal microcirculation was characterized by a low capillary density and a distinctive angioarchitecture. The possibility of peri-toneal microcirculatory assessment offers promise for the study of peritoneal (patho-)physiology and (monitoring or detection of) associated diseases., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

Human peritoneum is composed of mesothelial monolayer and stromal tissue containing microvasculature. Dissemination and infiltration of cancer cells to the peritoneum result in cancer peritoneal metastasis which is an important prognostic factor of intraperitoneal or intrapelvic carcinoma. To elucidate an initial metastatic mechanism of cancer cells, in vitro human peritoneal models are demanded. In this study, we created a three-dimensional artificial human peritoneal tissue (AHPT) harboring the blood or lymphatic vascular network by cell-accumulation technique. Morphological analysis demonstrated that AHPT had mesothelial monolayer with polygonal flat cells with apical microvilli, and stroma-like structure containing fibroblasts surrounded by extracellular matrix and blood or lymphatic vascular network. To assess AHPT as a tool for cancer peritoneal metastasis model, colon and ovarian cancer cells (HT-29 and SKOV3) were seeded onto AHPT. HT-29 cells showed poor metastatic characteristics forming thick clusters in mesothelial layer without invasion into stroma-like structure. On the other hand, SKOV3 cells rapidly invaded intercellular spaces between mesothelial cells and then spread over the stroma-like structure accompanying lymphatic invasion, showing aggressive metastatic characteristics. These results demonstrated that the metastatic dynamics of cancer cells with different characteristics are able to visualized by AHPT, suggesting that this tissue can be a powerful tool for the basic research of cancer peritoneal dissemination and metastasis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Spontaneous retroperitoneal haematoma (SRH) can be a life-threatening emergency presenting with hypovolaemic shock. SRH has been rarely reported with May-Thurner syndrome (MTS) where it occurs due to rupture of the iliac vein or venous collaterals. We report a case of MTS that presented with deep venous thrombosis of the left lower limb complicated by bilateral pulmonary embolism (PE) and a large pelvic haematoma. The simultaneous occurrence of a large pelvic haematoma and PE offered a therapeutic challenge. Successful endovascular management of the case is discussed in this report., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Vascular endothelial growth factor (VEGF) is implicated in the peritoneal membrane remodeling that limits ultrafiltration in patients on peritoneal dialysis (PD). Although the exact mechanism of VEGF induction in PD is unclear, VEGF concentrations in drained dialysate correlate with IL-6 levels, suggesting a link between these cytokines. Human peritoneal mesothelial cells (HPMCs), the main source of IL-6 and VEGF in the peritoneum, do not bear the cognate IL-6 receptor and are thus unable to respond to classic IL-6 receptor signaling. Here, we investigated whether VEGF release by HPMCs is controlled by IL-6 in combination with its soluble receptor (IL-6 trans-signaling). Although treatment with either IL-6 or soluble IL-6 receptor (sIL-6R) alone had no effect on VEGF production, stimulation of HPMCs with IL-6 in combination with sIL-6R promoted VEGF expression and secretion through a transcriptional mechanism involving STAT3 and SP4. Conditioned medium from HPMCs cultured with IL-6 and sIL-6R promoted angiogenic endothelial tube formation, which could be blocked by silencing SP4. In vivo , induction of peritoneal inflammation in wild-type and IL-6-deficient mice showed IL-6 involvement in the control of Sp4 and Vegf expression and new vessel formation, confirming the role of IL-6 trans-signaling in these processes. Taken together, these findings identify a novel mechanism linking IL-6 trans-signaling and angiogenesis in the peritoneal membrane., (Copyright © 2017 by the American Society of Nephrology.)

Purpose: To present the experience of repairing iatrogenic vesicovaginal fistulas (VVFs) using a rotational bladder flap and peritoneal interposition technique., Methods: Between January 2009 and June 2014, a total of 18 patients (mean age, 44.0 years; age range, 29-51 years) with VVFs were treated using a transperitoneal approach. All VVFs were complications of gynecologic procedures. Twelve patients experienced recurrent VVFs and one patient had a concomitant rectovaginal fistula after radiotherapy. The fistula was approached transabdominally. The peritoneum covering the bladder was isolated to expose the bladder and prepare for the interposition. The bladder was opened along the sagittal plane to the fistula and a bladder flap was rotated downward to fill the fistula defect. The vaginal defect was closed, then a flap using the isolated peritoneum was interposed and fixed between the vagina and bladder. A ureteral re-implantation was performed in one patient. All VVF procedures were performed by one urologist (SW). Repair of the rectovaginal fistula was performed by a general surgeon at the same time., Results: Seventeen patients (success rate = 94% [100% for primary cases and 92% for recurrent cases]) had no evidence of recurrent VVF at a mean follow-up of 20 months (range, 6-36 months). The only patient who had previously undergone a repair procedure failed., Conclusions: A transperitoneal approach with the use of a rotational bladder flap and peritoneal interposition might be a feasible and reliable procedure for surgical management of iatrogenic VVFs, especially in complicated cases. Neurourol. Urodynam. 35:934-938, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Objective: Perivascular cells, including pericytes, macrophages, smooth muscle cells, and other specialized cell types, like podocytes, participate in various aspects of vascular function. However, aside from the well-established roles of smooth muscle cells and pericytes, the contributions of other vascular-associated cells are poorly understood. Our goal was to ascertain the function of perivascular macrophages in adult tissues under nonpathological conditions., Approach and Results: We combined confocal microscopy, in vivo cell depletion, and in vitro assays to investigate the contribution of perivascular macrophages to vascular function. We found that resident perivascular macrophages are associated with capillaries at a frequency similar to that of pericytes. Macrophage depletion using either clodronate liposomes or antibodies unexpectedly resulted in hyperpermeability. This effect could be rescued when M2-like macrophages, but not M1-like macrophages or dendritic cells, were reconstituted in vivo, suggesting subtype-specific roles for macrophages in the regulation of vascular permeability. Furthermore, we found that permeability-promoting agents elicit motility and eventual dissociation of macrophages from the vasculature. Finally, in vitro assays showed that M2-like macrophages attenuate the phosphorylation of VE-cadherin upon exposure to permeability-promoting agents., Conclusions: This study points to a direct contribution of macrophages to vessel barrier integrity and provides evidence that heterotypic cell interactions with the endothelium, in addition to those of pericytes, control vascular permeability., (© 2016 American Heart Association, Inc.)

Clinical and animal studies suggest that peritoneal absorption of fluid and protein from dialysate to peritoneal tissue, and to blood and lymph circulation, occurs concomitantly with opposite flows of fluid and protein, i.e., from blood to dialysate. However, until now a theoretical explanation of this phenomenon has been lacking. A two-phase distributed model is proposed to explain the bidirectional, concomitant transport of fluid, albumin and glucose through the peritoneal transport system (PTS) during peritoneal dialysis. The interstitium of this tissue is described as an expandable two-phase structure with phase F (water-rich, colloid-poor region) and phase C (water-poor, colloid-rich region) with fluid and solute exchange between them. A low fraction of phase F is assumed in the intact tissue, which can be significantly increased under the influence of hydrostatic pressure and tissue hydration. The capillary wall is described using the three-pore model, and the conditions in the peritoneal cavity are assumed commencing 3 min after the infusion of glucose 3.86% dialysis fluid. Computer simulations demonstrate that peritoneal absorption of fluid into the tissue, which occurs via phase F at the rate of 1.8 ml/min, increases substantially the interstitial pressure and tissue hydration in both phases close to the peritoneal cavity, whereas the glucose-induced ultrafiltration from blood occurs via phase C at the rate of 15 ml/min. The proposed model delineating the phenomenon of concomitant bidirectional transport through PTS is based on a two-phase structure of the interstitium and provides results in agreement with clinical and experimental data.

Background and Objectives: Encapsulating peritoneal sclerosis (EPS) is a rare but serious and life-threatening complication of peritoneal dialysis (PD). However, the precise pathogenesis remains unclear; in addition, predictors and early diagnostic biomarkers for EPS have not yet to be established., Methods: Eighty-three peritoneal membrane samples taken at catheter removal were examined to identify pathological characteristics of chronic peritoneal deterioration, which promotes EPS in patients undergoing long-term PD treatment with low occurrence of peritonitis., Results: According to univariable logistic regression analysis of the pathological findings, thickness of the peritoneal membrane (P = 0.045), new membrane formation score (P = 0.006), ratio of luminal diameter to vessel diameter (L/V ratio, P<0.001), presence of CD31-negative vessels (P = 0.021), fibrin deposition (P<0.001), and collagen volume fraction (P = 0.018) were associated with EPS development. In analyses of samples with and without EPS matched for PD treatment period, non-diabetes, and PD solution, univariable analysis identified L/V ratio (per 0.1 increase: odds ratio (OR) 0.44, P = 0.003) and fibrin deposition (OR 6.35, P = 0.027) as the factors associated with EPS. L/V ratio was lower in patients with fibrin exudation than in patients without fibrin exudation., Conclusions: These findings suggest that damage to vascular endothelial cells, as represented by low L/V ratio, could be a predictive finding for the development of EPS, particularly in long-term PD patients unaffected by peritonitis.

Introduction: Lymphaticovenular anastomosis (LVA) has become an important procedure for the surgical treatment of lymphedema. In the past, the anatomy of the lymphatic system of animal models has been reported. However, to our knowledge, there have been few reports of animal models of LVA including training model. In this study, we report on a relatively simple and ideal animal LVA model based on peritoneal lymph ducts and veins., Patients and Methods: For 10 rats, diameters of lumbar lymphatic ducts and iliolumbar veins in the peritoneal cavity on both sides were measured, and LVA was performed. In addition, we measured the diameters of 28 lymphatic ducts and veins in 8 patients who had previously undergone LVA and compared the results with those obtained in this rat model., Results: The mean diameter of the lymphatic ducts was 0.61 mm, and the iliolumbar veins were 0.81 mm. On the other hand, the mean diameters of the 28 lymphatic ducts and veins of the 8 patients in whom we performed LVA were 0.58 and 0.76 mm, respectively. The differences in the diameters of the lymph vessels and veins between the rats and patients were not statistically significant., Conclusions: We report on an LVA model involving the use of the lumbar lymphatic duct and iliolumbar veins of rats. The diameter, nature, and placement of the anastomosis using this model are very similar to that noted during real human surgery. We believe that our rat model will be useful as a practical training model for LVA and in studies on postoperative changes in LVA.

The peritoneum plays an essential role in preventing abdominal frictions and adhesions and can be utilized as a dialysis membrane. Its physiological ultrastructure, however, has not yet been studied systematically. 106 standardized peritoneal and 69 omental specimens were obtained from 107 patients (0.1-60 years) undergoing surgery for disease not affecting the peritoneum for automated quantitative histomorphometry and immunohistochemistry. The mesothelial cell layer morphology and protein expression pattern is similar across all age groups. Infants below one year have a thinner submesothelium; inflammation, profibrotic activity and mesothelial cell translocation is largely absent in all age groups. Peritoneal blood capillaries, lymphatics and nerve fibers locate in three distinct submesothelial layers. Blood vessel density and endothelial surface area follow a U-shaped curve with highest values in infants below one year and lowest values in children aged 7-12 years. Lymphatic vessel density is much lower, and again highest in infants. Omental blood capillary density correlates with parietal peritoneal findings, whereas only few lymphatic vessels are present. The healthy peritoneum exhibits major thus far unknown particularities, pertaining to functionally relevant structures, and subject to substantial changes with age. The reference ranges established here provide a framework for future histomorphometric analyses and peritoneal transport modeling approaches.

Background: Ovarian cancer is mostly associated with pathologically regulated permeability of peritoneal vessels, leading to ascites. Here, we investigated the molecular regulation of endothelial permeability by the vascular endothelial growth factor (VEGF) and both tight and adherens junction proteins (VE-cadherin and claudin 5) with regards to the tumor biology of different ovarian cancer types., Methods: Serum and ascites samples before and after surgery, as well as peritoneal biopsies of 68 ovarian cancer patients and 20 healthy controls were collected. In serum and ascites VEGF protein was measured by ELISA. In peritoneal biopsies co-localization of VE-cadherin and claudin 5 was investigated using immunohistochemical dual staining. In addition, the gene expression of VE-cadherin and claudin 5 was quantified by Real-time PCR. Differences in VEGF levels, VE-cadherin and claudin 5 gene expression were analyzed in relation to various tumor characteristics (tumor stage, grading, histological subtypes, resection status after surgery) and then compared to controls. Furthermore, human primary ovarian cancer cells were co-cultured with human umbilical vein endothelial cells (HUVEC) and changes in VE-cadherin and claudin 5 were investigated after VEGF inhibition., Results: VEGF was significantly increased in tumor patients in comparison to controls and accumulates in ascites. The highest VEGF levels were found in patients diagnosed with advanced tumor stages, with tumors of poor differentiation, or in the group of solid / cystic-solid tumors. Patients with residual tumor after operation showed significantly higher levels of VEGF both before and after surgery as compared to tumor-free resected patients. Results of an immunohistochemical double-staining experiment indicated co-localization of VE-cadherin and claudin 5 in the peritoneal vasculature. Compared to controls, expression of VE-cadherin and claudin 5 was significantly suppressed in peritoneal vessels of tumor patients, but there were no significant differences regarding VE-cadherin and claudin 5 expression in relation to different tumor characteristics. A significant positive correlation was found between VE-cadherin and claudin 5 expression. VEGF inhibition in vitro was associated with significant increase in VE-cadherin and claudin 5., Conclusions: Our results indicate that increased peritoneal permeability in ovarian cancer is due to down-regulation of adhesion proteins via tumor derived VEGF. Advanced ovarian cancer with aggressive tumor biology may be associated with early dysregulation of vascular permeability leading to ascites. These patients may benefit from therapeutic VEGF inhibition.

Background/objectives: Patients with a short bowel and receiving parenteral nutrition (PN) have an increased risk of chronic cholestasis (CC). Restoration of bowel continuity after a mesenteric infarction results in PN requirements being reduced or stopped. This study aimed to determine the prevalence of CC and whether restoring bowel continuity reduced the risk of CC., Subjects/methods: A retrospective review of patients with a short bowel owing to mesenteric infarction from 2000 to 2012. CC was defined as two of bilirubin, alkaline phosphatase and gamma-glutamyl transferase being 1.5 times the upper limit of normal for >6 months., Results: We identified 104 (55 females, median age 54 years) patients. Seventy-three (70%) patients had restoration of bowel continuity; of these, 25 (34%) had abnormal liver biochemistry (liver function test (LFT)), with 15 (21%) having CC. Following restoration of bowel continuity, 8 (53%) of 15 patients with CC and 10 (100%) of 10 patients with abnormal LFT but not CC had a return of liver function within normal range within a year. Univariate analysis showed restoring bowel continuity (P=0.002) and cessation of PN (P=0.006) were associated with a reduction in prevalence of CC. Multivariate analysis showed that cessation of PN was a significant factor in reducing CC (P=0.02)., Conclusions: The prevalence of CC is 29% for patients with a short bowel receiving PN following a mesenteric infarction. CC resolves in 53% after continuity is restored, and this is most likely due to stopping or reducing the PN.

Background: Although laparoscopy may provide more detailed morphological and histological information about peritoneal damage, its significance in patients with long vintage of peritoneal dialysis (PD) is not elucidated., Methods: Findings in 12 patients with PD vintage of 7.3 (5.0-8.4) years who had undergone laparoscopy between 2007 and 2011 were reviewed. Macroscopic (peritoneal change, hypervascular change, adhesion, encapsulation) and histopathological peritoneal findings (interstitial fibrosis, microvascular change, fibrin deposition, inflammatory cell infiltration) were scored and summed as Macro-total score (Macro-TS) and Micro-total score (Micro-TS), respectively. Factors associated with these scores and the relationship between these scores were investigated., Results: Neither Macro-TS nor Micro-TS were related to PD vintage (p = 0.069 and p = 0.769, respectively); moreover, Macro-TS varied from patient to patient regardless of similar PD vintage. However, Macro-TS showed a significant association with duration of acidic dialysate (p = 0.003)., Conclusion: Macroscopic and microscopic findings via laparoscopy may help the assessment of peritoneal damage in patients with long PD vintage., (© 2015 S. Karger AG, Basel.)

Unlabelled: ♦, Background: The objective of this study was to examine the effects of a conventional dialysis solution and peritoneal catheter on leukocyte-endothelial cell interactions in the microcirculation of the parietal peritoneum in a subacute peritoneal dialysis (PD) mouse model. ♦, Methods: An intraperitoneal (IP) catheter with a subcutaneous injection port was implanted into mice and, after a 2-week healing period, the animals were injected daily for 6 weeks with a 2.5% dextrose solution. Intravital microscopy (IVM) of the parietal peritoneum microcirculation was performed 4 hours after the last injection of the dialysis solution. Leukocyte-endothelial cell interactions were quantified and compared with catheterized controls without dialysis treatment and naïve mice. ♦, Results: The number of rolling and extravascular leukocytes along with peritoneal fibrosis and neovascularization were significantly increased in the catheterized animals compared with naïve mice but did not significantly differ between the 2 groups of catheterized animals with sham injections or dialysis solution treatment. ♦, Conclusion: The peritoneal catheter implant increased leukocyte rolling and extravasation, peritoneal fibrosis and vascularization in the parietal peritoneum independently from the dialysis solution treatment., (Copyright © 2016 International Society for Peritoneal Dialysis.)

Purpose: Peritoneal fibrosis is almost uniform feature encountered in peritoneal dialysis patients. The transition of epithelial cells to mesenchymal phenotype, neovascularization, and consequently development of peritoneal fibrosis occur due to the involvement of peritoneal membrane by various insults such as uremia itself, peritonitis attacks, and exposure to bio-incompatible peritoneal dialysis fluids. Bevacizumab is a monoclonal antihuman antibody developed against vascular endothelial growth factor and can reduce fibrosis by preventing neovascularization. There has been no study so far that demonstrates the effect of bevacizumab on peritoneal fibrosis in a rat model., Methods: A total of 41 female Wistar albino rats were divided into six groups. The control group (C) received 0.9 % isotonic saline (2 ml/day) intraperitoneally (i.p) for 21 days. Chlorhexidine group (CH) received 15 % ethyl alcohol and 0.1 % chlorhexidine gluconate (CG) in saline (2 ml/day) i.p for 21 days. The resting group (R) received CG 2 ml/day i.p for 21 days. The bevacizumab-1 group (B1) received CG 2 ml/day i.p for 21 days and bevacizumab 2.5 mg/kg i.p as a single dose on day 21. The bevacizumab-2 group (B2) received CG 2 ml/day for 21 days and bevacizumab 2.5 mg/kg i.p on day 0 and day 21. The bevacizumab-3 group (B3) received bevacizumab 2.5 mg/kg i.p on day 0 and day 21. Peritoneal samples were taken from the left anterior abdominal wall. The thickness, vascularization, and fibrosis scores in the peritoneal samples were assessed using a light microscope., Results: On histopathological evaluations, peritoneum thicknesses, vascularization scores, and fibrosis significantly decreased in bevacizumab groups B1 and B2., Conclusion: Histopathologically, bevacizumab was proven to attenuate fibrotic process in experimental peritoneal sclerosis model.

Background: The present study sought to investigate the effects of Tarantula cubensis extract (TC; Theranekron®) on the histopathological scores of peritoneal wound healing after laparotomy in the rats., Methods: This study was designed to investigate the effects of Theranekron on the peritoneal wound healing after wound creation, on days9, 14, 19, 24 and 29 post-injury in rats. Twenty-four mature Wister-albino male rats were randomly divided into two groups. In the experimental group, TC was repeatedly injected subcutaneously (SC) over the lesion 9, 14,19 and 24 days after laparotomy, whereas the control group received only normal saline by subcutaneous injection and then the animal groups were euthanized9, 14, 19, 24, and 29 days after wounding respectively by intravenous injections of pentobarbital (50 mg/kg). Finally, assessment of the peritoneal wound healing between the groups was carried out by histopathologic data and statistical tests as Mann-Whitney U, Wilcoxon W and Z RESULTS: Histopathological examination indicated significant improvement in angiogenesis, re-epithelialization and less inflammatory response in comparison to control and also, revealed matured, compact and parallel deposition of collagen fibrils on day 29. So, at long term, treatment reduced the inflammation and increased the quality and rate of wound re- epithelialization compared to controls(P < 0.05). Furthermore, excluding the control group, rats exhibited the most pronounced effect on wound closure, with the statistically significant improvement in wound healing being seen at post-operative day 29. Moreover, collagen content on days 24 and 29 in the test group was found to be higher than in the healthy group. To warp up, treated groups had a significant increase in peritoneal wound healing area compared to the control group on all days (P < 0.05)., Conclusions: Our results suggested that Theranekron have delivered a novel therapeutic route for wound treatment in clinical practice., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2958770714954315 .

The largest and most complex serosal membrane in the body, the peritoneum, lines the abdominal cavity, and the abdominopelvic viscera. It is frequently involved in a variety of benign and malignant processes. While secondary involvement of the peritoneum is more common, primary tumors can be a diagnostic challenge. Knowledge of the anatomy is crucial in understanding the various pathologic processes. Cross-sectional imaging plays an important role in diagnosing and evaluating the extent of the disease processes. This article reviews the imaging anatomy of the peritoneum and mesentery and the common pathologies involving it.

Purpose: To investigate microvessel density (MVD), vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and interleukin-6 (IL-6) mRNA expression in peritoneal tissues, and their relationships with baseline peritoneal transport in uremia., Methods: Thirty uremic patients with a peritoneal dialysis catheter were selected in the Department of Nephrology in Dalian Central Hospital, Liaoning, China between 2010 and 2012. Peritoneal specimens were harvested for assessment of MVD, VEGF, eNOS, and IL-6 mRNA expression. One month after continuous ambulatory peritoneal dialysis, a peritoneal equilibration test was conducted. According to the 4-h peritoneal dialysate and plasma creatinine ratio (D/P Cr), patients were divided into high (n=16) and low (n=14) transport groups., Results: General clinical data of high and low transport groups were similar (P>0.05). The MVD in peritoneal tissues was significantly higher in the high than in the low transport group (P<0.05). Correspondingly, VEGF (P<0.01), eNOS (P<0.01), and IL-6 (P<0.05) mRNA expression levels were significantly higher in the high as compared the low transport groups. Correlation analysis showed that the baseline D/P Cr was positively correlated with MVD and VEGF, eNOS, and IL-6 mRNA expression levels in the peritoneum (r=0.506, 0.646, 0.638, and 0.686, respectively; P<0.01)., Conclusions: Uremic patients display differences in peritoneal microvascular endothelial function and microinflammatory states before peritoneal dialysis. Patients of the high transport group have higher MVD, increased expression of endothelial function markers (VEGF and eNOS), and the microinflammatory marker (IL-6). These observations are closely related to high baseline peritoneal transport.

Peritoneal membrane pathology limits long-term peritoneal dialysis (PD). Here, we tested whether JAK/STAT signaling is implicated and if its attenuation might be salutary. In cultured mesothelial cells, PD fluid activated, and the pan-JAK inhibitor P6 reduced, phospho-STAT1 and phospho-STAT3, periostin secretion, and cleaved caspase-3. Ex vivo, JAK was phosphorylated in PD effluent cells from long-term but not new PD patients. MCP-1 and periostin were increased in PD effluent in long term compared with new patients. In rats, twice daily, PD fluid infusion induced phospho-JAK, mesothelial cell hyperplasia, inflammation, fibrosis, and hypervascularity after 10 days of exposure to PD fluid. Concomitant instillation of a JAK1/2 inhibitor virtually completely attenuated these changes. Thus, our studies directly implicate JAK/STAT signaling in the mediation of peritoneal membrane pathology as a consequence of PD.

Background: The heparan sulfate proteoglycan syndecan-1 (CD138) was shown to regulate inflammatory responses by binding chemokines and cytokines and interacting with adhesion molecules, thereby modulating leukocyte trafficking to tissues. The objectives of this study were to examine the expression of syndecan-1 and its role in leukocyte recruitment and chemokine presentation in the microcirculation underlying the parietal peritoneum., Methods: Wild-type BALB/c and syndecan-1 null mice were stimulated with an intraperitoneal injection of Staphylococcus aureus LTA, Escherichia coli LPS or TNFα and the microcirculation of the parietal peritoneum was examined by intravital microscopy after 4 hours. Fluorescence confocal microscopy was used to examine syndecan-1 expression in the peritoneal microcirculation using fluorescent antibodies. Blocking antibodies to adhesion molecules were used to examine the role of these molecules in leukocyte-endothelial cell interactions in response to LTA. To determine whether syndecan-1 co-localizes with chemokines in vivo, fluorescent antibodies to syndecan-1 were co-injected intravenously with anti-MIP-2 (CXCL2), anti-KC (CXCL1) or anti-MCP-1 (CCL2)., Results and Conclusion: Syndecan-1 was localized to the subendothelial region of peritoneal venules and the mesothelial layer. Leukocyte rolling was significantly decreased with LPS treatment while LTA and TNFα significantly increased leukocyte adhesion compared with saline control. Leukocyte-endothelial cell interactions were not different in syndecan-1 null mice. Antibody blockade of β2 integrin (CD18), ICAM-1 (CD54) and VCAM-1 (CD106) did not decrease leukocyte adhesion in response to LTA challenge while blockade of P-selectin (CD62P) abrogated leukocyte rolling. Lastly, MIP-2 expression in the peritoneal venules was not dependent on syndecan-1 in vivo. Our data suggest that syndecan-1 is expressed in the parietal peritoneum microvasculature but does not regulate leukocyte recruitment and is not necessary for the presentation of the chemokine MIP-2 in this tissue.

Ischemia-induced adhesion is very common after surgery, and leads to severe abdominal adhesions. Unfortunately, many existing barrier agents used for adhesion prevention have only limited success. The objective of this study is to evaluate the efficacy of biodegradable and thermosensitive poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) micelles for the prevention of postoperative ischemia-induced adhesion. We found that the synthesized PCL-PEG-PCL copolymer could self-assemble in an aqueous solution to form micelles with a mean size of 40.1 ± 2.7 nm at 10°C, and the self-assembled micelles could instantly turn into a nonflowing gel at body temperature. In vitro cytotoxicity tests suggested that the copolymer showed little toxicity on NIH-3T3 cells even at amounts up to 1,000 μg/mL. In the in vivo test, the postsurgical ischemic-induced peritoneal adhesion model was established and then treated with the biodegradable and thermosensitive micelles. In the control group (n=12), all animals developed adhesions (mean score, 3.58 ± 0.51), whereas three rats in the micelles-treated group (n=12) did not develop any adhesions (mean score, 0.67 ± 0.78; P<0.001, Mann-Whitney U-test). Both hematoxylin and eosin and Masson trichrome staining of the ischemic tissues indicated that the micelles demonstrated excellent therapeutic effects on ischemia-induced adhesion. On Day 7 after micelle treatment, a layer of neo-mesothelial cells emerged on the injured tissues, which confirmed the antiadhesion effect of the micelles. The thermosensitive micelles had no significant side effects in the in vivo experiments. These results suggested that biodegradable and thermosensitive PCL-PEG-PCL micelles could serve as a potential barrier agent to reduce the severity of and even prevent the formation of ischemia-induced adhesions.