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Peritoneal adhesion is a common complication of abdominal and pelvic surgery that can cause various clinical symptoms, including abdominal pain, intestinal obstruction, and female infertility, significantly impacting patient quality of life. Animal models of peritoneal adhesion are important tools for studying the mechanisms of adhesion formation and evaluating the effectiveness of prevention and treatment. Various methods for constructing animal models of peritoneal adhesion include physical injury, chemical injury, ischemia, infection, foreign body stimulation, and simulated surgery; however, none can fully simulate peritoneal adhesion in patients clinically. Therefore, this review aimed to explore previous methods used to construct peritoneal adhesion animal models and summarize their principles, characteristics, and applications. Similarly, it summarizes macroscopic and microscopic evaluation indicators, such as peritoneal adhesion gross assessment, histological scoring, and molecular markers. On the basis of this, we proposed a new animal model of peritoneal adhesion that simulates the factors contributing to peritoneal adhesion formation in clinical surgery. peritoneal adhesion formation was stable and standardized using our proposed model, providing a foundation for the establishment and application of peritoneal adhesion animal models., Competing Interests: Conflicts of Interest/Disclosure The authors have no conflicts of interests or disclosures to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Encapsulated peritoneal sclerosis (EPS) is a serious complication in patients undergoing peritoneal dialysis (PD). Neutral-pH dialysate is associated with less peritoneal damage and a lower incidence of EPS than conventional PD solution. However, monitoring for peritoneal damage and predicting EPS remain important during PD therapy., Methods: We measured the mesothelial cell area, dialysate-to-plasma ratio of creatinine after 4 h, and concentrations of the potential biological markers effluent fibrin degradation products (eFDPs), cancer antigen-125, and interleukin-6 in the effluent dialysate from patients who had been undergoing PD therapy for > 5 years in our hospital. These biomarkers were obtained from the drainage fluid of the final measurement of peritoneal equilibration testing before withdrawal from PD therapy. The concentrations of these potential biomarkers were measured in 39 patients who withdrew from PD therapy and were enrolled in the study., Results: Three participants developed EPS after withdrawing PD. The dialysate-to-plasma ratio of creatinine, area of mesothelial cells, and interleukin-6 appearance rate in participants who developed EPS tended to be higher than those in patients who did not, but there were no significant differences. Significantly more eFDPs were in participants who developed EPS than in those who did not (138.5 ± 15.1 vs. 32.9 ± 7.4 µg/mL, P = 0.002). There was no difference in the cancer antigen-125 appearance rate between the groups. A cut-off value of eFDPs ≥ 119.1 µg/mL was optimal for predicting EPS (P = 0.006, specificity = 0.972, sensitivity = 1.000)., Conclusion: This study shows that eFDPs may be a useful biological marker for predicting EPS in patients undergoing PD using neutral-pH dialysate., Competing Interests: Declarations. Conflict of interest: No funding was received for conducting this study. Kumiko Torisu is participating in a course funded by the Baxter Healthcare Corporation., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

During long-term peritoneal dialysis, peritoneal fibrosis (PF) often happens and results in ultrafiltration failure, which directly leads to the termination of dialysis. The accumulation of extracellular matrix produced from an increasing number of myofibroblasts was a hallmark characteristic of PF. To date, glucose degradation products (GDPs, i.e., methylglyoxal (MGO)) that appeared during the heating and storage of the dialysate are considered to be key components to initiating PF, but how GDPs lead to the activation of myofibroblast in fibrotic peritoneum has not yet been fully elucidated. In this study, mesothelial cell line (MeT-5A) and fibroblast cell line (MRC-5) were used to investigate the transcriptomic and proteomic changes to unveil the underlying mechanism of MGO-induced PF. Our transcriptomic data from the MGO-stimulated mesothelial cells showed upregulation of genes involved in pro-inflammatory, apoptotic, and fibrotic pathways. While no phenotypic changes were noted on fibroblasts after direct MGO, supernatant from MGO-stimulated mesothelial cells promoted fibroblasts to change into proto-myofibroblasts, activated fibroblasts in the first stage toward myofibroblasts. In conclusion, this study showed that MGO-stimulated mesothelial cells promoted fibroblast-to-proto-myofibroblast transition; however, additional involvement of other factors or cells (e.g., macrophages) may be needed to complete the transformation into myofibroblasts.

Previous abdominal surgery (PAS) increases risk of small bowel obstruction (SBO) due to adhesions, and appendectomy (appy) is an independent risk factor for abdominal adhesion-related complications. Peritoneal inflammation, e.g., acute appendicitis (AA), causes formation of reactive ascitic fluid (rA) that activates peritoneum surface mesothelial cells (MCs) to form adhesions. Pathologic adhesions may arise if restoration of MC-regulated fibrinolysis and secretion of glycocalyx (GCX) are disrupted. Proteins affecting these processes may originate from peritoneal rA. This is a prospective observational IRB-approved study at three Level 1 trauma centers where rA is collected prior to surgical intervention for non-perforated AA or adhesiolysis for SBO. Samples from 48 appy and 15 SBO patients were used to treat human MCs and subjected to quantification of 85 inflammatory mediators. Results were compared between patients with surgically naïve abdomens (naïve) and patients with >1 PAS. Select rA caused MCs to form clusters of fibroblastic cells, extracellular matrix fibers (FIB), and secretion of GCX. PAS and naïve patient rA fluids were clustered into "fiber-GCX" (FIB-GCX) groups: highFIB-highGCX, highFIB-lowGCX, noFIB-highGCX, noFIB-lowGCX, and noFIB-noGCX. Between groups, 26 analytes were differentially abundant including innate immune response, wound healing, and mucosal defense proteins. Factors that contributed to the differences between groups were rA-induced highFIB and history of PAS. Overall, PAS patient rA showed a muted immune response compared to rA from naïve patients. Our data suggest that abdominal surgery may negatively impact future immune responses in the abdomen. Further, quantifying immunomodulators in peritoneal rA may lead to the development a personalized approach to post-surgical adhesion treatment and prevention., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Hausburg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Peritoneal adhesion (PA) refers to the abnormal adhesion of the peritoneum either with the peritoneum itself or with tissues and organs that is caused by abdominopelvic surgery, abdominal infection or peritoneal inflammation. PA is associated with various clinical complications, such as abdominal pain and distension, intestinal obstruction, gastrointestinal disorders and female infertility, and adversely affects the quality of life of patients. Macrophages are essential for PA formation and can undergo polarization into classically activated macrophages (M1) and alternatively activated macrophages (M2), which are influenced by the peritoneal microenvironment. By releasing proinflammatory cytokines and reactive oxygen species, M1 macrophages promote peritoneal inflammatory reactions and the resultant formation of adhesion. In contrast, M2 macrophages secrete anti-inflammatory cytokines and growth factors to inhibit PA formation and to promote repair and healing of peritoneal tissues, and thereby play a significant anti-inflammatory role. This review comprehensively explores the function and mechanism of macrophages and their subtypes in PA formation to gain insight into the prevention and treatment of PA based on the modulation of macrophages., (© 2024 the Australian and New Zealand Society for Immunology, Inc.)

Introduction: Clinical outcomes for the treatment of peritoneal carcinomatosis (PC) have remained suboptimal. Microsphere-based intraperitoneal chemotherapy has shown considerable potential in preclinical studies. However, due to the complications associated with peritoneal adhesions, there has been a lack of comprehensive reviews focusing on the progress of microsphere applications in the treatment of PC., Areas Covered: We provide an overview of the current clinical treatment strategies for PC and analyze the potential advantages of microspheres in this context. Regarding the issue of peritoneal adhesions induced by microspheres, we investigate the underlying mechanisms and propose possible solutions. Furthermore, we outline the future directions for the development of microsphere-based therapies in the treatment of PC., Expert Opinion: Microspheres formulated with highly biocompatible materials to the peritoneum, such as sodium alginate, gelatin, or genipin, or with an optimal particle size (4 ~ 30 μm) and lower molecular weights (10 ~ 57 kDa), can prevent peritoneal adhesions and improve drug distribution. To further enhance the antitumor efficacy, enhancing the tumor penetration capability and specificity of microspheres, optimizing intraperitoneal distribution, and addressing tumor resistance have demonstrated significant potential in preclinical studies, offering new therapeutic prospects for the treatment of PC.

Background: Peritoneal dissemination of ovarian cancer (OvCa) can be largely attributed to the formation of a metastatic microenvironment driven by tumoral exosomes. Here, we aimed to elucidate the mechanisms through which exosomal annexin A2 (ANXA2) derived from OvCa cells induces an HPMC phenotypic shift in favour of peritoneal metastasis., Methods: Immunohistochemistry and orthotopic and intraperitoneal OvCa xenograft mouse models were used to clarify the relationship between tumour ANXA2 expression and peritoneal metastasis. Exosomes were isolated from OvCa cell lines via ultracentrifugation. Functional experiments on cell proliferation and motility, and western blot were performed to investigate the activation of HPMCs and its impact on tumour cell in vitro. High-throughput transcriptional sequencing and rescue experiments in which ANXA2 inhibitor (LCKLSL) or the toll-like receptor 2 (TLR2) inhibitor (C29) was used to co-culture the HPMCs with exosome were employed to identify the crucial functional molecules through which exosomal ANXA2 activates HPMCs. The impact of exosomal ANXA2-activated HPMCs on tumour progression was assessed via functional experiments., Results: Primary OvCa samples with high ANXA2 expression exhibited a stronger tendency to metastasize to the abdominal cavity. Tumoral ANXA2 promoted OvCa peritoneal metastasis through the secretion of exosomes carrying ANXA2. ANXA2-loaded exosomes activated HPMCs through exosomal ANXA2 binding to TLR2, shifting the phenotype of HPMCs towards mesenchymal cells, increasing their migration and invasion capacities, and elevating the expression of lipocalin 2 (LCN2). High LCN2 expression in HPMCs promoted OvCa cell adhesion, proliferation, motility, and lipid metabolism reprogramming., Conclusion: Exosomal ANXA2 secreted by tumour cells activates HPMCs and induces the expression of LCN2, which in turn promotes the peritoneal metastasis of OvCa., Competing Interests: Declarations. Ethics approval and consent to participate: This study was performed in accordance with the Declaration of Helsinki. All clinical specimens and information involved in this study provided informed consent before collection and were approved by The Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology. All animal study procedures were approved by The Animal Care and Use Committee of Wuhan Youdu Biotechnology Co., Ltd. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: To evaluate the peritoneal histopathological changes and culture after the use of intravenous meropenem and intra-abdominal inoculation of 10% aqueous extract of anacardiaceae, in elderly rat model after autogenous fecal peritonitis induced., Methods: Thirty 18-month-old Wistar rats received induction of autogenous fecal peritonitis and then were stratified into two groups: study I, treated with meropenem (40 mg/kg); and study II, treated with meropenem (40 mg/kg) and intraperitoneal 10% aqueous extract of anacardiaceae. Animals were monitored for 15 days until euthanasia. Peritoneal fragments were collected for histopathological and culture. The study was approved by Ethics Committee., Results: None study-II animals died, while in study I, one died before euthanasia. In study II, 20% of the animals showed histopathological changes, none positive peritoneal culture, but one blood culture was positive (10%). In study I, 50% of the animals presented histopathological changes, 40% positive peritoneal cultures, and 50% positive blood cultures. All results when evaluated in the morbidity score showed better outcome for study-II group (p = 0,175)., Conclusion: The use of meropenem associated with intraperitoneal 10% aqueous anacardiaceae extract after induction of autogenous fecal peritonitis in elderly rats showed better outcome in the set of histopathological changes, negative peritoneal and blood cultures, when compared with the use of meropenem isolated.

Long-term exposure of the peritoneum to peritoneal dialysate results in pathophysiological changes in the anatomical organization of the peritoneum and progressive development of peritoneal fibrosis. This leads to a decline in peritoneal function and ultrafiltration failure, ultimately necessitating the discontinuation of peritoneal dialysis, severely limiting the potential for long-term maintenance. Additionally, encapsulating peritoneal sclerosis, a serious consequence of peritoneal fibrosis, resulting in patients discontinuing PD and significant mortality. The causes and mechanisms underlying peritoneal fibrosis in patients undergoing peritoneal dialysis remain unknown, with no definitive treatment available. However, abnormal activation of the immune system appears to be involved in altering the structure of the peritoneum and promoting fibrotic changes. Macrophage infiltration and polarization are key contributors to pathological injury within the peritoneum, showing a strong correlation with the epithelial-to-mesenchymal transition of mesothelial cells and driving the process of fibrosis. This article discusses the role and mechanisms underlying macrophage activation-induced peritoneal fibrosis resulting from PD by analyzing relevant literature from the past decade and provides an overview of recent therapeutic approaches targeting macrophages to treat this condition., 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 © 2024 Wang, Zhang, Ma, Zhuang, Lu, Miao, Lu, Cui and Cui.)

Aim: Ultrasound-guided percutaneous core needle biopsy is an important technique in diagnosing mesenteric involvement. Diagnostic results were compared with pre-biopsy CT findings. The purpose of this study was to determine the diagnostic efficiency of omental lesion biopsies performed under ultrasound guidance and to investigate the relationship between pre-biopsy diagnostic CT findings., Materials and Methods: Demographic data of 70 patients who underwent omental biopsy under ultrasound guidance in our clinic between August 2015 and July 2023, the presence of a primary malignancy focus during the investigations conducted during the research, biopsy histopathology results, and pre-biopsy CT findings were retrospectively reviewed., Results: This retrospective study included who underwent omental biopsy under ultrasound guidance, 48 (69%) were female, and 22 (31%) were male, with an average age of 61 (age range 15-95), and an average body mass index [BMI] of 27.7 ± 6.9. Five (7%) of the 70 biopsy procedures were not pathologically diagnostic. Diagnostic results were compared with pre-biopsy CT findings. In all omental lesions, the percentage of omental infiltrative involvement in diagnostic CT was subjectively evaluated by two radiologists. 65 patients diagnosed pathologically, 47 (67%) were malignant, and 18 (26%) were benign. No complications occurred., Conclusion: Peritoneal biopsies under ultrasound guidance for mesenteric diseases detected on CT are a reliable procedure that can be easily applied. Ultrasonography imaging helps identify appropriate locations for targeted biopsies before deep percutaneous biopsy, increasing diagnostic accuracy, especially when omental lesions appear as infiltrative thickenings., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Peritoneal metastasis (PM) in gastric cancer (GC) is associated with poor prognosis and significant morbidity. We sought to understand the genomic, transcriptomic, and tumor microenvironment (TME) features that contribute to peritoneal organotropism in GC., Methods: We conducted a comprehensive multi-omic analysis of 548 samples from 326 patients, including primary tumors, matched normal tissues; peritoneal metastases, and adjacent-normal peritoneal tissues. We used whole exome sequencing, whole transcriptome sequencing, and digital spatial profiling to investigate molecular alterations, gene expression patterns, and TME characteristics associated with PM., Results: Our analysis identified specific genomic alterations in primary tumors, including mutations in ELF3, CDH1, and PIGR, and TME signatures, such as stromal infiltration and M2 macrophage enrichment, associated with increased risk of PM. We observed distinct transcriptional programs and immune compositions in GCPM compared with liver metastases, highlighting the importance of the TME in transcoelomic metastasis. We found differential expression of therapeutic targets between primary tumors and PM, with lower CLDN18.2 and FGFR2b expression in PM. We unravel the roles of the TME in niche reprogramming within the peritoneum, and provide evidence of pre-metastatic niche conditioning even in early GC without clinical PM. These findings were further validated using a humanized mouse model, which demonstrated niche remodeling in the peritoneum during transcoelomic metastasis., Conclusion: Our study provides a comprehensive molecular characterization of GCPM and unveils key biological principles underlying transcoelomic metastasis. The identified predictive markers, therapeutic targets, and TME alterations offer potential avenues for targeted interventions and improved patient outcomes., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: To investigate the effects and mechanisms of LCZ696, an angiotensin receptor-neprilysin inhibitor (ARNI), on epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells and on macrophage M2 polarization., Methods: We examined the effects of LCZ696 in a 4.25% high glucose peritoneal dialysis fluid (PDF)-induced peritoneal fibrosis (PF) mouse model, and explored the mechanisms of LCZ696 on human peritoneal mesothelial cells (HPMCs) stimulated by TGF-β1 (5 ng/mL) and on Raw264.7 cells stimulated by IL-4 (10 ng/mL). To further elucidate the mechanism, we treated HPMCs with the conditioned medium of Raw264.7 cells., Results: LCZ696 effectively improved PF and inhibited the process of EMT in PDF mice. In vitro , LCZ696 also significantly alleviated the EMT of TGF-β1 induced HPMCs, although there was no statistically significant difference when compared to the Valsartan treatment group. Moreover, LCZ696 ameliorates the increased expression of Snail and Slug, two nuclear transcription factors that drive the EMT. Mechanistically, TGF-β1 increased the expression of TGFβRI, p-Smad3, p-PDGFRβ and p-EGFR, while treatment with LCZ696 abrogated the activation of TGF-β/Smad3, PDGFRβ and EGFR signaling pathways. Additionally, exposure of Raw264.7 to IL-4 results in increasing expression of Arginase-1, CD163 and p-STAT6. Treatment with LCZ696 inhibited IL-4-elicited M2 macrophage polarization by inactivating the STAT6 signaling pathway. Furthermore, we observed that LCZ696 inhibits EMT by blocking TGF-β1 secretion from M2 macrophages., Conclusion: Our study demonstrated that LCZ696 improves PF and ameliorates TGF-β1-induced EMT of HPMCs by blocking TGF-β/Smad3, PDGFRβ and EGFR pathways. Meanwhile, LCZ696 also inhibits M2 macrophage polarization by regulating STAT6 pathway.

Peritoneal dialysis (PD) is a widely used sustainable kidney replacement therapy. Prolonged use of PD fluids is associated with mesothelial-mesenchymal transition, peritoneal fibrosis, and eventual ultrafiltration (UF) failure. However, the impact of pressure on the peritoneum remains unclear. In the present study, we hypothesized increased pressure is a potential contributing factor to peritoneal fibrosis and investigated the possible mechanisms. In vitro experiments found that pressurization led to a mesenchymal phenotype, the expression of fibrotic markers and inflammatory factors in human mesothelial MeT-5A cells. Pressure also increased cell proliferation and augmented cell migration potential in MeT-5A cells. The mouse PD model and human peritoneum equilibrium test (PET) data both showed a positive association between higher pressure and increased small solute transport, along with decreased net UF. Mechanistically, we found that significant upregulation of CD44 in mesothelial cells upon pressurization. Notably, the treatment of CD44 neutralizing antibodies prevented pressure-induced phenotypic changes in mesothelial cells, while a CD44 inhibitor oligo-fucoidan ameliorated pressure-induced peritoneal thickening, fibrosis, and inflammation in PD mice. To conclude, intraperitoneal pressure results in peritoneal fibrosis in PD via CD44-mediated mesothelial changes and inflammation. CD44 blockage can be utilized as a novel preventive approach for PD-related peritoneal fibrosis and UF failure.

Background: Different strategies have been proposed to prevent lymphocele (LC) formation after radical prostatectomy (RARP) with pelvic lymph node dissection (PLND). According to several recently published randomized control trials (RCTs) on the topic, peritoneal reconfiguration appears to be associated with promising results. This systematic review aimed to assess the impact of peritoneal reconfiguration on LC formation in patients undergoing RARP and PLND., Methods: A comprehensive bibliographic search was conducted in August 2023. Studies assessing patients with prostate cancer undergoing RARP with PLND (P) and concomitant peritoneal reconfiguration (I) compared or not with other techniques (C) to prevent LC formation (O) were included. Original prospective and retrospective studies (S) were selected. LC and symptomatic LC rates were chosen as co-primary outcomes. Only RCTs were included in the meta-analysis., Results: Eleven studies investigating 2991 patients were included in the systematic review, and five RCTs evaluating 1712 subjects were deemed eligible for meta-analysis. Peritoneal flap (PF) was the most common surgical technique used for LC prevention (9 studies). A significantly lower likelihood of LC was observed after PF (OR 0.82, 95% CI 0.27-1.37, I 2  = 74.54%), with no significant difference in terms of symptomatic LC (OR 0.21, 95% CI -0.41-0.84, I 2  = 0%). Probability of LC-related complications (OR 0.36, 95% CI 0.04-0.67, I 2  = 0%), Clavien-Dindo ≥ 3 overall complications (OR 0.61, 95% CI 0.21-1.0, I 2  = 0%), and Clavien-Dindo ≥ 3 LC-related complications (OR 0.98, 95% CI 0.29-1.67, I 2  = 0%) were significantly lower after PF., Conclusions: PF after RARP with PLND reduces LC formation, LC-related complications, and severe postoperative adverse events., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Peritoneal fibrosis is a serious complication of long-term peritoneal dialysis, often resulting in functional deterioration and withdrawal from therapy. Mesenchymal stem cells (MSCs) have demonstrated immunomodulatory and antifibrotic effects in various models. This meta-analysis evaluated the efficacy of MSCs therapy in animal models of peritoneal fibrosis., Methods: A comprehensive search of PubMed, the Cochrane Library, Web of Science, and EMBASE was conducted for studies published up to April 27, 2024. Two independent reviewers (LQZ and WMC) screened studies for inclusion, extracted data, and analyzed outcomes using RevMan 5.3 and STATA 17.0., Result: Fifteen studies met the inclusion criteria. MSC therapy significantly reduced inflammatory cytokines, including IL-6, TGF-β (SMD = -1.79, 95% CI: -2.32, -1.25, p  < 0.00001), and TNF-α (SMD = -1.57, 95% CI: -2.71, -0.44, p  = 0.006) levels. Additionally, MSCs reduced submesothelial thickness (MD = -63.14, 95% CI: -78.52, -47.76, p  < 0.00001), Collagen I and Collagen III levels. MSCs treatment also improved ultrafiltration capacity (MD = 1.21, 95% CI: 0.64, 1.77, p  < 0.0001), D/D0 of glucose and E-cadherin levels. However, no significant differences were observed in VEGF, D/P of Na, D/P of BUN, D/P of protein, or glucose mass transfer between the MSCs treatment group and the control group., Conclusion: MSC therapy significantly improves peritoneal function and attenuates fibrotic and inflammatory responses in animal models. These findings highlight the potential of MSCs as a promising therapeutic strategy for managing peritoneal fibrosis in clinical settings.

Background: The quality of life of patients receiving long-term peritoneal dialysis (PD) is significantly impacted by the onset of peritoneal fibrosis (PF), and one of the pathological changes is mesothelial-mesenchymal transition (MMT). In this study, we investigated the potential roles of miR-454-3p and signal transducer and activator of transcription 3 (STAT3) in the progression of peritoneal MMT and the underlying mechanisms., Methods: Peritoneums were collected to detect morphology via hematoxylin-eosin staining and differentially expressed miRNAs were detected via RT-qPCR. PD effluent-derived cell populations in the peritoneal cavity were isolated from the effluents of 20 PD patients to determine miR-454-3p, STAT3, and MMT markers via Western blotting and RT-qPCR. The relationship between miR-454-3p and STAT3 was examined via a dual-luciferase reporter assay. Western blotting and RT-qPCR were utilized to evaluate the expression of STAT3, MMT markers, and glycolytic enzymes. Immunofluorescence staining revealed the localization and expression of MMT markers and STAT3., Results: MiR-454-3p was downregulated in the peritoneums and PD effluent-derived cell populations of long-term PD patients. High glucose (HG) treatment promoted HMrSV5 cell MMT and glycolysis. MiR-454-3p overexpression alleviated HG-induced MMT and suppressed the expression of STAT3 and glycolytic enzymes. In contrast, the miR-454-3p inhibitor exacerbated HG-induced MMT and promoted the expression of glycolytic enzymes and STAT3. Moreover, STAT3 was the target of miR-454-3p., Conclusions: This study demonstrated the protective role of miR-454-3p in HG-induced MMT and glycolysis in HMrSv5 cells, suggesting that miR-454-3p may prevent MMT by suppressing glycolytic enzymes via the STAT3/PFKFB3 pathway in the HG environment.

Increasing evidence suggests that peritoneal fibrosis induced by peritoneal dialysis (PD) is linked to oxidative stress. However, there are currently no effective interventions for peritoneal fibrosis. In the present study, we explored whether adding caffeic acid phenethyl ester (CAPE) to peritoneal dialysis fluid (PDF) improved peritoneal fibrosis caused by PD and explored the molecular mechanism. We established a peritoneal fibrosis model in Sprague-Dawley rats through intraperitoneal injection of PDF and lipopolysaccharide (LPS). Rats in the PD group showed increased peritoneal thickness, submesothelial collagen deposition, and the expression of TGFβ1 and α-SMA. Adding CAPE to PDF significantly inhibited PD-induced submesothelial thickening, reduced TGFβ1 and α-SMA expression, alleviated peritoneal fibrosis, and improved the peritoneal ultrafiltration function. In vitro , peritoneal mesothelial cells (PMCs) treated with PDF showed inhibition of the AMPK/SIRT1 pathway, mitochondrial membrane potential depolarization, overproduction of mitochondrial reactive oxygen species (ROS), decreased ATP synthesis, and induction of mesothelial-mesenchymal transition (MMT). CAPE activated the AMPK/SIRT1 pathway, thereby inhibiting mitochondrial membrane potential depolarization, reducing mitochondrial ROS generation, and maintaining ATP synthesis. However, the beneficial effects of CAPE were counteracted by an AMPK inhibitor and siSIRT1. Our results suggest that CAPE maintains mitochondrial homeostasis by upregulating the AMPK/SIRT1 pathway, which alleviates oxidative stress and MMT, thereby mitigating the damage to the peritoneal structure and function caused by PD. These findings suggest that adding CAPE to PDF may prevent and treat peritoneal fibrosis.

Purpose: The intraperitoneal leak of urine is considered as a major cause of peritoneal inflammatory reaction that could lead to paralytic ileus. Our aim was to document the effect of urine on the peritoneal surface., Methods: Seven white minipigs (one control-six tests) underwent standardized general anaesthesia. In three test pigs urine was aspirated from the bladder and instilled in the peritoneal cavity. In the remaining three pigs a continuous urine leak was created through section of the ureter. At 4 and 10 h laparoscopic harvesting of slices of the parietal peritoneum at the level of the Douglas pouch, lateral pelvic wall and subdiaphragmatic area was performed. Ileum slices were also obtained at 10 h. The slices were microscopically evaluated for inflammatory infiltrate (INI) of the peritoneum according to the Sydney system classification., Results: The presence of urine in the peritoneum induces distention of the ileum. At 4 h, a light-moderate INI was observed to two pigs of both test groups but not to the control pig. At 10 h a light-moderate INI appeared in the peritoneal slices of the control pig. Moreover, three out of six pigs of both test groups showed some degree of INI of the parietal peritoneum. The histologic evaluation of the slices of the distended ileum did not reveal INI., Conclusions: The intraperitoneal urine induces distention of the bowel but no inflammation of the visceral peritoneum in the short term (10 h). Other than inflammation mechanisms through which the urine induces small ileum distention should be investigated., Competing Interests: Declarations. Author disclosure: Nothing to disclose. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Peritoneal dialysis (PD) serves as a home-based kidney replacement therapy with increasing utilization across the globe. However, long-term use of high-glucose-based PD solution incites repeated peritoneal injury and inevitable peritoneal fibrosis, thus compromising treatment efficacy and resulting in ultrafiltration failure eventually. In the present study, we utilized human mesothelial MeT-5A cells for the in vitro experiments and a PD mouse model for in vivo validation to study the pathophysiological mechanisms underneath PD-associated peritoneal fibrosis. High-glucose PD solution (Dianeal 4.25%, Baxter) increased protein expression of mesothelial-mesenchymal transition (MMT) markers, such as N-cadherin and α-SMA in MeT-5A cells, whereas it decreased catalase expression and stimulated the production of reactive oxygen species (ROS). Furthermore, macrophage influx and increased serum pro-inflammatory cytokines, such as IL-1β, MCP-1, and TNF-α, were observed in the PD mouse model. Interestingly, we discovered that oligo-fucoidan, an oligosaccharide extract from brown seaweed, successfully prevented PD-associated peritoneal thickening and fibrosis through antioxidant effect, downregulation of MMT markers, and attenuation of peritoneal and systemic inflammation. Hence, oligo-fucoidan has the potential to be developed into a novel preventive strategy for PD-associated peritoneal fibrosis.

Peritoneal fibrosis has been linked to hypoxia-inducible factor 1-alpha (HIF-1α) as well as O-linked-N-acetylglucosaminylation (O-GlcNAcylation) in peritoneal dialysis (PD). Genistein, recognized for its HIF-1α inhibitory and antifibrotic effects, presents a potential intervention against peritoneal mesothelial-mesenchymal transition (MMT) as well as fibrosis in PD. This study employed human peritoneal mesothelial cells (HPMCs) together with adenine-induced chronic kidney disease (CKD) rats undergoing peritoneal dialysis to explore Genistein's role in high glucose-induced peritoneal MMT and fibrosis. Our findings reveal that Genistein exerts anti-MMT and anti-fibrotic effects by inhibiting HIF-1α in HPMCs under high glucose conditions. Genistein inhibited O-GlcNAcylation status of HIF-1α through the mTOR/O-GlcNAc transferase (OGT) pathway, promoting its ubiquitination as well as the subsequent proteasomal degradation. In adenine-induced CKD rats undergoing peritoneal dialysis, Genistein suppressed the mTOR/OGT expression and reduced the abundance of O-GlcNAcylation along with HIF-1α in the peritoneum. Additionally, Genistein protected against increased peritoneal thickness, fibrosis, and angiogenesis, while improving peritoneal function. Based on our results, it could be inferred that Genistein might inhibit the abundance of HIF-1α via the mTOR/OGT pathway, thereby ameliorating MMT as well as fibrosis in PD., (© 2024. The Author(s).)

Ovarian cancer (OvCa) is one of the most lethal gynecological malignancies, and most patients are diagnosed at advanced stage with peritoneal dissemination. Although age at diagnosis is considered an independent prognostic factor, its impact on peritoneal recurrence after combined cytoreductive surgery and chemotherapy is not clear. The objective of this study was to investigate the impact of aging on peritoneal recurrence from stealth dissemination and gain insight of the pathophysiology of OvCa in elderly patients. A total of 243 patients with pT2b-pT3 epithelial ovarian who achieved complete surgery, no-residual tumor at first surgery, were selected to be analyzed the risk of peritoneal seeding and recurrence. We found that age over 65 years was independently associated with an increased risk of peritoneum-specific (PS) recurrence (. Furthermore, pT3 stages and positive ascites cytology also worsen the PS-relapse-free survival. Collectively, our findings suggest that age, especially over 65 years, predicts reduced peritoneum-specific tumor recurrence in patients with advanced ovarian cancer after complete cytoreduction surgery, particularly those with pT3 tumors and positive ascites cytology., (© 2024. The Author(s).)

Background: Robotic-assisted surgery (particularly with the da Vinci Surgical System) has revolutionized urological interventions. The advent of the Versius Surgical System introduces a compelling alternative. This study compares outcomes of extraperitoneal robot-assisted radical prostatectomy (eRARP) using da Vinci and Versius, presenting the largest case series to date., Methods: A retrospective analysis of 106 consecutive patients undergoing eRARP (July 2021-July 2023) with da Vinci and Versius. Surgical techniques involved extraperitoneal approaches, with a single surgeon ensuring consistency. Baseline characteristics, perioperative outcomes, and pathology results were analyzed., Results: Baseline characteristics were comparable between da Vinci and Versius groups. While no significant differences were observed in overall operative time, estimated blood loss, and length of hospital stay, variations were noted in pelvic lymphadenectomy rates and nerve-sparing procedures. Pathology results revealed no significant disparities in International Society of Urological Pathology (ISUP) grades and positive surgical margins. However, a notable difference emerged in pathological N stage, with Versius showing a higher percentage of positive lymph nodes., Conclusions: This study provides a comprehensive comparative analysis of da Vinci and Versius in eRARP, representing the largest case series to date. While overall outcomes were similar, nuances in lymphadenectomy rates and Pathological N stage merit attention. Ongoing research and longer-term follow-up will refine our understanding, guiding urological surgeons in optimal robotic system selection.

Background: In this study, we aimed to establish a stable and standardized animal model of peritoneal adhesions., Methods: Forty-eight male Sprague-Dawley rats were randomly divided (n = 12 each) into blank control, classic cecum sidewall, ischemic button, and cecum-sidewall suture groups. The modified American Fertility Society adhesion score was used on postoperative day 7 to evaluate adhesions. Sixty male Sprague-Dawley rats were used to dynamically observe the adhesion characteristics of cecum-sidewall ischemic injury suture model at different time points (n = 60, randomly divided into groups a-e with 12 rats each). The modified American Fertility Society and Zühlke histologic scoring systems, hematoxylin-eosin staining, Masson staining, and computed tomography of the abdomen were used to evaluate adhesions on postoperative days 1, 3, 5, 7, and 14., Results: No peritoneal adhesions were observed in the blank control group on postoperative day 7. In the classic cecum sidewall group, 8 rats had inconsistent adhesions, which had a modified American Fertility Society adhesion score of 2.25 ± 1.96. All rats in the ischemic button and cecum-sidewall suture groups developed significant adhesions with modified American Fertility Society scores of 3.08 ± 1.31 and 4.67 ± 0.78, respectively. When the modified American Fertility Society score was used, statistically significant differences were observed between the classic cecum sidewall groups and cecum-sidewall suture groups and between the ischemic button groups and cecum-sidewall suture groups. All animals in groups a-e developed adhesions; adhesion scores increased gradually with time., Conclusions: The cecum-sidewall ischemic injury suture model is a stable and standardized animal model of peritoneal adhesions., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Large non-apoptotic vesicles released from the plasma membrane protrusions are classified as large-EVs (LEVs). However, the triggers of LEV secretion and their functions in tumors remain unknown., Methods: Coculture system of cancer cells, peritoneal mesothelial cells (PMCs), and macrophages (MΦs) was conducted to observe cell-cell contact-mediated LEV secretion. Lineage tracing of PMCs was performed using Wt1 CreERT2 -tdT nu mice to explore the effects of LEVs on PMCs in vivo, and lymphangiogenesis was assessed by qRT-PCR and flow-cytometry., Results: In peritoneal dissemination, cancer cells expressing Ephrin-B (EFNB) secreted LEVs upon the contact with PMCs expressing ephrin type-B (EphB) receptors, which degraded mesothelial barrier by augmenting mesothelial-mesenchymal transition. LEVs were incorporated in subpleural MΦs, and these MΦs transdifferentiated into lymphatic endothelial cells (LEC) and integrated into the lymphatic vessels. LEC differentiation was also induced in PMCs by interacting with LEV-treated MΦs, which promoted lymphangiogenesis. Mechanistically, activation of RhoA-ROCK pathway through EFNB reverse signaling induced LEV secretion. EFNBs on LEVs activated EphB forward signaling in PMC and MΦs, activating Akt, ERK and TGF-β1 pathway, which were indispensable for causing MMT and LEC differentiation. LEVs accelerated peritoneal dissemination and lymphatic invasions by cancer cells. Blocking of EFNBs on LEVs using EphB-Fc-fusion protein attenuated these events., Conclusions: EFNB high cancer cells scattered LEVs when they attached to PMCs, which augmented the local reactions of PMC and MΦ (MMT and lymphangiogenesis) and exaggerated peritoneal dissemination., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The mesothelium is a non-adhesive protective surface that lines the serosal cavities and organs within the body. The glycocalyx is a complex structure that coats the outer layer of the mesothelium. However, due to the limitations of conventional fixation techniques, studies on glycans are limited. In this study, lectin staining of frozen tissues was performed to investigate the diversity of glycans in the glycocalyx of mesothelial cells in mice. Datura stramonium lectin (DSL), which recognizes lactosamine and binds to Galectin-3 and -1, was broadly bound to the mesothelial cells of the visceral and parietal peritoneum but not to the pancreas, liver, intestine, or heart. Furthermore, human mesothelial cells in the omentum and parietal peritoneum were positive for DSL. Erythrina cristagalli lectin binding was specific to mesothelial cells in the parietal peritoneum, that is, the pleura, diaphragm, and peritoneum. Intriguingly, surface sialylation, the key element in reducing peritoneal dissemination and implantation, and promoting ascites formation by ovarian carcinoma cells, was much higher in the parietal peritoneum than in the omentum. These findings revealed slight differences in the glycans of mesothelial cells of different organs, which may be related to clinical diseases. These results also suggest that there may be differences in the functions of parietal and visceral mesothelial cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

One of the most common causes of peritoneal dialysis withdrawal is ultrafiltration failure which is characterized by peritoneal membrane thickening and fibrosis. Although previous studies have demonstrated the inhibitory effect of p38 MAPK inhibitors on peritoneal fibrosis in mice, it was unclear which specific cells contribute to peritoneal fibrosis. To investigate the role of p38 MAPK in peritoneal fibrosis more precisely, we examined the expression of p38 MAPK in human peritoneum and generated systemic inducible p38 MAPK knockout mice and macrophage-specific p38 MAPK knockout mice. Furthermore, the response to lipopolysaccharide (LPS) was assessed in p38 MAPK-knocked down RAW 264.7 cells to further explore the role of p38 MAPK in macrophages. We found that phosphorylated p38 MAPK levels were increased in the thickened peritoneum of both human and mice. Both chlorhexidine gluconate (CG)-treated systemic inducible and macrophage-specific p38 MAPK knockout mice ameliorated peritoneal thickening, mRNA expression related to inflammation and fibrosis, and the number of αSMA- and MAC-2-positive cells in the peritoneum compared to CG control mice. Reduction of p38 MAPK in RAW 264.7 cells suppressed inflammatory mRNA expression induced by LPS. These findings suggest that p38 MAPK in macrophages plays a critical role in peritoneal inflammation and thickening., (© 2024. The Author(s).)

Epithelial-to-mesenchymal transition (EMT) is considered as one of the senescence processes; reportedly, antisenescence therapies effectively reduce EMT. Some models have shown antisenescence effects with the use of sodium-glucose cotransporter 2 (SGLT2) inhibitor. Therefore, our study investigated the antisenescence effects of empagliflozin as an SGLT2 inhibitor in a peritoneal fibrosis model and their impact on EMT inhibition. For in vitro study, human peritoneal mesothelial cells (HPMCs) were isolated and grown in a 96-well plate. The cell media were exchanged with serum-free M199 medium with d-glucose, with or without empagliflozin. All animal experiments were carried out in male mice. Mice were randomly classified into three treatment groups based on peritoneal dialysis (PD) or empagliflozin. We evaluated changes in senescence and EMT markers in HPMCs and PD model. HPMCs treated with glucose transformed from cobblestone to spindle shape, resulting in EMT. Empagliflozin attenuated these morphological changes. Reactive oxygen species production, DNA damage, senescence, and EMT markers were increased by glucose treatment; however, cotreatment with glucose and empagliflozin attenuated these changes. For the mice with PD, an increase in thickness, collagen deposition, staining for senescence, or EMT markers of the parietal peritoneum was observed, which, however, was attenuated by cotreatment with empagliflozin. p53, p21, and p16 increased in mice with PD compared with those in the control group; however, these changes were decreased by empagliflozin. In conclusion, empagliflozin effectively attenuated glucose-induced EMT in HPMCs through a decrease in senescence. Cotreatment with empagliflozin improved peritoneal thickness and fibrosis in PD. NEW & NOTEWORTHY Epithelial-to-mesenchymal transition (EMT) is considered one of the senescence processes. Antisenescence therapies may effectively reduce EMT in peritoneal dialysis models. Human peritoneal mesothelial cells treated with glucose show an increase in senescence and EMT markers; however, empagliflozin attenuates these changes. Mice undergoing peritoneal dialysis exhibit increased senescence and EMT markers, which are decreased by empagliflozin. These findings suggest that empagliflozin may emerge as a novel strategy for prevention or treatment of peritoneal fibrosis.

Background: Amphoterin-induced gene and open reading frame 2 (AMIGO2) have been reported to be related to the prognosis of colorectal, gastric, and cervical cancer. However, their association with ovarian cancer remains unclear. This study aimed to elucidate the role of AMIGO2 in ovarian cancer., Methods: AMIGO2 expression was evaluated using immunohistochemistry in patients with ovarian serous carcinoma. We validated in vitro studies using four serous ovarian cancer cell lines and in vivo studies using a murine model., Results: The AMIGO2-high group had significantly shorter progression-free survival (PFS) than the AMIGO2-low group. The predictive index of the AMIGO2-high group was considerably higher than that of the AMIGO2-low group. The rate of complete cytoreductive surgery was lower in the AMIGO2-high group than in the AMIGO2-low group. Moreover, in vitro studies revealed that four serous ovarian cancer cell lines exhibited AMIGO2 expression and adhesion to mesothelial cells. Adhesion to mesothelial cells was attenuated by AMIGO2 knockdown in SKOV3 and SHIN3 cells. Furthermore, AMIGO2 downregulation in SKOV3 cells significantly suppressed peritoneal dissemination in the murine model., Conclusion: These results suggest that high AMIGO2 expression in serous ovarian carcinoma cells contributes to a poor prognosis by promoting peritoneal metastasis through enhanced cell adhesion to mesothelial cells., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Endometriosis is a chronic inflammatory disease that causes debilitating pelvic pain in women. Macrophages are considered to be key players in promoting disease progression, as abundant macrophages are present in ectopic lesions and elevated in the peritoneum. In the present study, we examined the role of GATA6 + peritoneal macrophages on endometriosis-associated hyperalgesia using mice with a specific myeloid deficiency of GATA6. Lesion induction induced the disappearance of TIM4 hi MHCII lo residential macrophages and the influx of increased Ly6C + monocytes and TIM4 lo MHCII hi macrophages. The recruitment of MHCII hi inflammatory macrophages was extensive in Mac Gata6 KO mice due to the severe disappearance of TIM4 hi MHCII lo residential macrophages. Ki67 expression confirmed GATA6-dependent proliferative ability, showing different proliferative phenotypes of TIM4 + residential macrophages in Gata6 f/f and Mac Gata6 KO mice. Peritoneal proinflammatory cytokines were elevated after lesion induction. When cytokine levels were compared between Gata6 f/f and Mac Gata6 KO mice, TNFα at day 21 in Gata6 f/f mice was higher than in Mac Gata6 KO mice. Lesion induction increased both abdominal and hind paw sensitivities. Gata6 f/f mice tended to show higher sensitivity in the abdomen after day 21. Elevated expression of TRPV1 and CGRP was observed in the dorsal root ganglia after ELL induction in Gata6 f/f mice until days 21 and 42, respectively. These results support that peritoneal GATA6 + macrophages are involved in the recruitment and reprogramming of monocyte-derived macrophages. The extensive recruitment of monocyte-derived macrophages in Mac Gata6 KO mice might protect against inflammatory stimuli during the resolution phase, whereas GATA6 deficiency did not affect lesion initiation and establishment at the acute phase of inflammation. GATA6 + residential macrophages act to sustain local inflammation in the peritoneum and sensitivities in the neurons, reflecting endometriosis-associated hyperalgesia., 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 © 2024 Shi, MacLean and Hayashi.)

The characteristic feature of chronic peritoneal damage in peritoneal dialysis (PD) is a decline in ultrafiltration capacity associated with pathological fibrosis and angiogenesis. The pathogenesis of peritoneal fibrosis is attributed to bioincompatible factors of PD fluid and peritonitis. Uremia is associated with peritoneal membrane inflammation that affects fibrosis, neoangiogenesis, and baseline peritoneal membrane function. Net ultrafiltration volume is affected by capillary surface area, vasculopathy, peritoneal fibrosis, and lymphangiogenesis. Many inflammatory cytokines induce fibrogenic growth factors, with crosstalk between macrophages and fibroblasts. Transforming growth factor (TGF)-β and vascular endothelial growth factor (VEGF)-A are the key mediators of fibrosis and angiogenesis, respectively. Bioincompatible factors of PD fluid upregulate TGF-β expression by mesothelial cells that contributes to the development of fibrosis. Angiogenesis and lymphangiogenesis can progress during fibrosis via TGF-β-VEGF-A/C pathways. Complement activation occurs in fungal peritonitis and progresses insidiously during PD. Analyses of the human peritoneal membrane have clarified the mechanisms by which encapsulating peritoneal sclerosis develops. Different effects of dialysates on the peritoneal membrane were also recognized, particularly in terms of vascular damage. Understanding the pathophysiologies of the peritoneal membrane will lead to preservation of peritoneal membrane function and improvements in technical survival, mortality, and quality of life for PD patients.

Disease spread in the abdomen and pelvis generally occurs in a predictable pattern in relation to anatomic landmarks and fascial planes. Anatomically, the abdominopelvic cavity is subdivided into several smaller spaces or compartments by key ligaments and fascial planes. The abdominal cavity has been traditionally divided into peritoneal, retroperitoneal, and pelvic extraperitoneal spaces. Recently, more clinically relevant classifications have evolved. Many pathologic conditions affect the abdominal cavity, including traumatic, inflammatory, infectious, and neoplastic processes. These abnormalities can extend beyond their sites of origin through various pathways. Identifying the origin of a disease process is the first step in formulating a differential diagnosis and ultimately reaching a final diagnosis. Pathologic conditions differ in terms of pathways of disease spread. For example, simple fluid tracks along fascial planes, respecting anatomic boundaries, while fluid from acute necrotizing pancreatitis can destroy fascial planes, resulting in transfascial spread without regard for anatomic landmarks. Furthermore, neoplastic processes can spread through multiple pathways, with a propensity for spread to noncontiguous sites. When the origin of a disease process is not readily apparent, recognizing the spread pattern can allow the radiologist to work backward and ultimately arrive at the site or source of pathogenesis. As such, a cohesive understanding of the peritoneal anatomy, the typical organ or site of origin for a disease process, and the corresponding pattern of disease spread is critical not only for initial diagnosis but also for establishing a road map for staging, anticipating further disease spread, guiding search patterns and report checklists, determining prognosis, and tailoring appropriate follow-up imaging studies. © RSNA, 2024 Supplemental material is available for this article.

At least one-third of patients with epithelial ovarian cancer (OC) present ascites at diagnosis and almost all have ascites at recurrence especially because of the propensity of the OC cells to spread in the abdominal cavity leading to peritoneal metastasis. The influence of ascites on the development of pre-metastatic niches, and on the biological mechanisms leading to cancer cell colonization of the mesothelium, remains poorly understood. Here, we show that ascites weakens the mesothelium by affecting the morphology of mesothelial cells and by destabilizing their distribution in the cell cycle. Ascites also causes destabilization of the integrity of mesothelium by modifying the organization of cell junctions, but it does not affect the synthesis of N-cadherin and ZO-1 by mesothelial cells. Moreover, ascites induces disorganization of focal contacts and causes actin cytoskeletal reorganization potentially dependent on the activity of Rac1. Ascites allows the densification and reorganization of ECM proteins of the mesothelium, especially fibrinogen/fibrin, and indicates that it is a source of the fibrinogen and fibrin surrounding OC spheroids. The fibrin in ascites leads to the adhesion of OC spheroids to the mesothelium, and ascites promotes their disaggregation followed by the clearance of mesothelial cells. Both αV and α5β1 integrins are involved. In conclusion ascites and its fibrinogen/fibrin composition affects the integrity of the mesothelium and promotes the integrin-dependent implantation of OC spheroids in the mesothelium., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 CY Cergy Paris University. Published by Elsevier Inc. All rights reserved.)

Background: The clinical importance of positive peritoneal cytology results in patients with pancreatic ductal adenocarcinomas remains controversial. We evaluated the prognosis of these patients and the predictive preoperative risk factors for positive peritoneal cytology results., Methods: We retrospectively reviewed patients who underwent curative-intent surgery at our institution between May 2010 and June 2020. Preoperative risk factors for positive peritoneal cytology results were identified using logistic regression analysis. A scoring model was constructed using the total number of significant independent predictors for positive peritoneal cytology results., Results: Of 233 patients, 18 (7.7%) had positive peritoneal cytology results. The recurrence-free survival and cancer-specific survival were markedly worse in patients with positive peritoneal cytology results than in those with negative peritoneal cytology results (recurrence-free survival: 6.0 months vs. 16.6 months, p = 0.050; cancer-specific survival: 19.4 months vs. 47.5 months, p = 0.034). Tumor location (odds ratio: 3.760, 95% confidence interval: 1.099-11.818, p = 0.023), tumor size > 25 mm (odds ratio: 3.410, 95% confidence interval: 1.031-11.277, p = 0.046), preoperative serosal invasion (odds ratio: 5.193, 95% confidence interval: 1.099-24.531, p = 0.038), and preoperative carcinoembryonic antigen level > 5.6 ng/mL (odds ratio: 3.816, 95% confidence interval: 1.248-10.667, p = 0.019) were identified as significant independent predictive factors. Our predictive model's optimal cutoff and positive predictive values for positive peritoneal cytology results were 3 and 27.9%, respectively., Conclusions: The indications for curative-intent surgery should be considered carefully in patients with high-risk factors for positive peritoneal cytology results., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Peritoneal fibrosis, a common complication observed in long-term peritoneal dialysis patients, can gradually lead to ultrafiltration failure and the development of encapsulating peritoneal sclerosis. Although mechanisms of peritoneal fibrosis have been proposed, effective therapeutic options are unsatisfactory. Recently, several tyrosine kinase inhibitors have proven to be anti-fibrosis in rodent models. To assess the potential therapeutic effects of tyrosine kinase inhibitors on peritoneal fibrosis in the larger animal model, a novel porcine model of peritoneal fibrosis induced by 40 mM methylglyoxal in 2.5 % dialysate was established, and two different doses (20 mg/kg and 30 mg/kg) of sorafenib were given orally to evaluate their therapeutic efficacy in this study. Our results showed that sorafenib effectively reduced adhesions between peritoneal organs and significantly diminished the thickening of both the parietal and visceral peritoneum. Angiogenesis, vascular endothelial growth factor A production, myofibroblast infiltration, and decreased endothelial glycocalyx resulting from dialysate and methylglyoxal stimulations were also alleviated with sorafenib. However, therapeutic efficacy in ameliorating loss of mesothelial cells, restoring decreased ultrafiltration volume, and improving elevated small solutes transport rates was limited. In conclusion, this study demonstrated that sorafenib could potentially be used for peritoneal fibrosis treatment, but applying sorafenib alone might not be sufficient to fully rescue methylglyoxal-induced peritoneal defects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Peritoneal dialysis is a common treatment for end-stage renal disease, but complications often force its discontinuation. Preventive treatments for peritoneal inflammation and fibrosis are currently lacking. Cyclo(His-Pro) (CHP), a naturally occurring cyclic dipeptide, has demonstrated protective effects in various fibrotic diseases, yet its potential role in peritoneal fibrosis (PF) remains uncertain. In a mouse model of induced PF, CHP was administered, and quantitative proteomic analysis using liquid chromatography-tandem mass spectrometry was employed to identify PF-related protein signaling pathways. The results were further validated using human primary cultured mesothelial cells. This analysis revealed the involvement of histone deacetylase 3 (HDAC3) in the PF signaling pathway. CHP administration effectively mitigated PF in both peritoneal tissue and human primary cultured mesothelial cells, concurrently regulating fibrosis-related markers and HDAC3 expression. Moreover, CHP enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) while suppressing forkhead box protein M1 (FOXM1), known to inhibit Nrf2 transcription through its interaction with HDAC3. CHP also displayed an impact on spleen myeloid-derived suppressor cells, suggesting an immunomodulatory effect. Notably, CHP improved mitochondrial function in peritoneal tissue, resulting in increased mitochondrial membrane potential and adenosine triphosphate production. This study suggests that CHP can significantly prevent PF in peritoneal dialysis patients by modulating HDAC3 expression and associated signaling pathways, reducing fibrosis and inflammation markers, and improving mitochondrial function., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

The current study examines the effects of linalool in preventing postoperative abdominal adhesions. Twenty male Wistar rats were randomly divided into four groups. (1) Sham: in this group, the abdomen was approached, and without any manipulations, it was sutured. (2) Control: rats in this group underwent a surgical procedure to induce adhesions. This involved making three incisions on the right abdominal side and removing a 1×1-cm piece of the peritoneum on the left abdominal side. (3) Treatment groups: these groups underwent the same surgical procedure as the control group to induce adhesions. Animals in these groups received linalool orally with doses of 50 and 100 mg/kg, respectively, for a period of 14 days. Moreover, rats in the sham and control groups received normal saline via gavage for 14 days. The evaluation of TNF-α, TGF-β, VEGF, and caspase 3 was performed using western blot and IHC methods. Furthermore, oxidative stress biomarkers such as MDA, TAC, GSH, and NO were assessed in the peritoneal adhesion tissue. The findings revealed that linalool significantly reduced peritoneal adhesions by reducing TNF-α, TGF-β, VEGF, and caspase 3 levels. Moreover, MDA concentration was significantly decreased, while NO, TAC, and GSH levels were notably increased. Overall, linalool was effective in preventing adhesion formation and reduced inflammation, angiogenesis, apoptosis, and oxidative stress. Therefore, linalool as a potent antioxidant is suggested for reducing postoperative adhesions in rats., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The link between post-operative adhesion development and epigenetic modifications is important in understanding the mechanism behind their formation. The aim of this study was to determine whether epigenetic differences exist between primary fibroblasts of normal peritoneum and adhesion tissues isolated from the same patient(s)., Methods: DNA from fibroblasts isolated from normal peritoneum and adhesion tissues was isolated using Qiagen's EZ1 Advanced Kit. Methylation patterns of genes were quantified and compared in both cell lines using the Infinium Human Methylation 27 BeadChip ® system (Illumina, San Diego, CA, USA)., Results: A total of 7364 genes had been found to manifest significantly different DNA methylation levels in adhesion fibroblasts as compared to normal peritoneal fibroblasts (P<0.01). A total of 1685 genes were found to have increased DNA methylation by 50% in adhesion compared to peritoneal fibroblasts, and were enriched in gene ontology categories, glycoprotein, and defense response. Furthermore, 1287 genes were found to have decreased DNA methylation patterns with enriched gene ontology categories, "homeobox," and transcription factor activity in adhesion fibroblasts., Conclusions: Epigenetic differences in fibroblasts isolated from normal peritoneum and adhesion tissues were observed. Future studies focusing on the precise role of these genes in the development of postoperative adhesions will allow us to more fully appreciate regulatory mechanisms leading to adhesion development, thereby establishing targets for therapeutic interventions to prevent or limit adhesion development.

Epithelial-to-mesenchymal transition (EMT) is one of the main causes of peritoneal fibrosis. However, the pathophysiological mechanisms of EMT, specifically its relationship with autophagy, are still unknown. This study aimed to evaluate the role of autophagy in transforming growth factor-beta 1 (TGF-β1)-induced EMT in human peritoneal mesothelial cells (HPMCs). Primary cultured HPMCs were treated with TGF-β1 (2 and 5 ng/mL) and changes in autophagy markers and the relationship between autophagy and EMT were evaluated. We also identified changes in EMT- and autophagy-related signaling pathways after autophagy and NADPH oxidase 4 (NOX4) inhibition. TGF-β1 increased the generation of NOX4 and reactive oxygen species (ROS) in HPMCs, resulting in mitochondrial damage. Treatment with GKT137831 (20 μM), a NOX1/4 inhibitor, reduced ROS in the mitochondria of HPMC cells and reduced TGF-β1-induced mitochondrial damage. Additionally, the indirect inhibition of autophagy by GKT137831 (20 μM) downregulated TGF-β1-induced EMT, whereas direct inhibition of autophagy using 3-methyladenine (3-MA) (2 mM) or autophagy-related gene 5 (ATG5) gene silencing decreased the TGF-β1-induced EMT in HPMCs. The suppressor of mothers against decapentaplegic 2/3 (Smad2/3), autophagy-related phosphoinositide 3-kinase (PI3K) class III, and protein kinase B (Akt) pathways, and mitogen-activated protein kinase (MAPK) signaling pathways, such as extracellular signal-regulated kinase (ERK) and P38, were involved in TGF-β1-induced EMT. Autophagy and NOX4 inhibition suppressed the activation of these signaling pathways. Direct inhibition of autophagy and its indirect inhibition through the reduction of mitochondrial damage by upstream NOX4 inhibition reduced EMT in HPMCs. These results suggest that autophagy could serve as a therapeutic target for the prevention of peritoneal fibrosis in patients undergoing peritoneal dialysis., (© 2024. The Author(s).)

Postoperative intra-abdominal adhesions represent a significant post-surgical problem. Its complications can cause a considerable clinical and cost burden. Herein, our study aimed to investigate the effect of Everolimus on peritoneal adhesion formation after inducing adhesions in rats. In this experimental study, adhesion bands were induced by intraperitoneal injection of 3 ml of 10% sterile talc solution in 64 male albino rats. The first group served as the control group. The second one received oral Prednisolone (1 mg/kg/day), the third received Everolimus (0.1 mg/kg/day), and group four received both drugs with similar dosages for four consecutive weeks. The formation of adhesion bands was qualitatively graded according to the Nair classification. The rats in the control group had extensive adhesions between the abdominal wall and the organs. Regarding substantial adhesion formation, 50% (8/16) of animals in the control group had substantial adhesions, while this rate in the groups receiving Prednisolone, Everolimus, and combination treatment was 31%, 31%, and 31%, respectively. Also, 68.75% (5/11) of the Prednisolone recipients had insubstantial adhesions, the same as Everolimus recipients, while in the combination group, 66.66% (10/15) rats had insubstantial adhesions. Everolimus demonstrated satisfactory results in reducing the rates of induced peritoneal adhesion in an experimental model, similar to Prednisolone and superior to a combination regime., (© 2024. The Author(s).)

Peritoneal dialysis is a widely used method for treating kidney failure. However, over time, the peritoneal structure and function can deteriorate, leading to the failure of this therapy. This deterioration is primarily caused by infectious and sterile inflammation. Sterile inflammation, which is inflammation without infection, is particularly concerning as it can be subtle and often goes unnoticed. The onset of sterile inflammation involves various pathological processes. Peritoneal cells detect signals that promote inflammation and release substances that attract immune cells from the bloodstream. These immune cells contribute to the initiation and escalation of the inflammatory response. The existing literature extensively covers the involvement of different cell types in the sterile inflammation, including mesothelial cells, fibroblasts, endothelial cells, and adipocytes, as well as immune cells such as macrophages, lymphocytes, and mast cells. These cells work together to promote the occurrence and progression of sterile inflammation, although the exact mechanisms are not fully understood. This review aims to provide a comprehensive overview of the signals from both stromal cells and components of immune system, as well as the reciprocal interactions between cellular components, during the initiation of sterile inflammation. By understanding the cellular and molecular mechanisms underlying sterile inflammation, we may potentially develop therapeutic interventions to counteract peritoneal membrane damage and restore normal function., 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 © 2024 Su, Zou, Su, Chen, Yang, An, Yang, Tang, Liu and Yao.)

Longitudinal evolution of peritoneal protein loss (PPL), a reflection of hydrostatic pressure-driven leak of plasma proteins through the large-pore pathway, is not clear. Time on PD causes loss of mesothelial cells, vasculopathy, and increased thickness of the submesothelial fibrous layer. Are these structural changes associated with progressive increase of PPL, in a parallel with the rise in the D/P creatinine? The aim of the present study was to identify longitudinal changes of PPL over time. This single-center, longitudinal study included 52 peritoneal dialysis (PD) patients with a median follow-up of 26.5 months, evaluated at two different time points with a minimum interval of 6 months. Repeated measures analysis was performed using paired sample t-test or the nonparametric Wilcoxon signed-rank test, depending on the distribution. After a median interval of 15.5 months, lower levels of residual renal function and urine volume, lower Kt/V, and creatinine clearance were found. D/P creatinine and PPL were stable, but a decrease in ultrafiltration was present. Systemic inflammation, nutrition, and volume overload showed no significant change with time on PD. Analysis of a subpopulation with over 48 months between initial and subsequential assessment (n = 11) showed again no difference in inflammation, nutritional and hydration parameters from baseline, but importantly PPL decreased after more than 4 years on PD (mean difference 1.2 g/24, p = 0.033). D/P creatinine and dip of sodium remained unchanged. The absence of deleterious effects of time on PD is reassuring, pointing to the benefit of updated PD prescription, including the standard use of more biocompatible solutions towards membrane preservation and adjusted prescription avoiding overhydration and inflammation while maintaining nutritional status. After controlling for confounders, PPL may act as a biomarker of acquired venous vasculopathy, even if small pore fluid transport rates and free water transport are preserved., (© 2024 Wiley Periodicals LLC.)

Peritoneal fibrosis is a common pathological response to long-term peritoneal dialysis (PD) and a major cause for PD discontinuation. Understanding the cellular and molecular mechanisms underlying the induction and progression of peritoneal fibrosis is of great interest. In our study, in vitro study revealed that signal transducer and activator of transcription 3 (STAT3) is a key factor in fibroblast activation and extracellular matrix (ECM) synthesis. Furthermore, STAT3 induced by IL-6 trans-signalling pathway mediate the fibroblasts of the peritoneal stroma contributed to peritoneal fibrosis. Inhibition of STAT3 exerts an antifibrotic effect by attenuating fibroblast activation and ECM production with an in vitro co-culture model. Moreover, STAT3 plays an important role in the peritoneal fibrosis in an animal model of peritoneal fibrosis developed in mice. Blocking STAT3 can reduce the peritoneal morphological changes induced by chlorhexidine gluconate. In conclusion, our findings suggested STAT3 signalling played an important role in peritoneal fibrosis. Therefore, blocking STAT3 might become a potential treatment strategy in peritoneal fibrosis., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Peritoneal fibrosis (PF) is a primary reason for discontinuing peritoneal dialysis, which involves characteristic changes of peritoneal mesothelial cells (PMCs). We previously reported preventive effects of implanting human epithelial-like PMCs (P-Epi) for mouse PF caused by mechanical peritoneum scrapings. In the present study, we analysed the preventive effects of culture supernatant of P-Epi in PF. Concentrated culture supernatant of P-Epi or human fibroblast-like PMCs (P-Fibro) or vehicles was injected into nude mice that had undergone mechanical scraping of the parietal and visceral peritoneum, and thickness and amount of adhesions were analysed. Although increased peritoneal adhesions and peritoneum thickening were observed in the vehicle-injected positive control group compared to the sham operation group, fewer number of adhesions and less thickness were observed in the mice treated with culture supernatant of P-Epi, but not P-Fibro, compared to the vehicle-injected positive controls. Immunofluorescent analysis revealed that the expression of extracellular matrix, type I collagen and fibronectin, was lower in the mice treated with culture supernatant of P-Epi than in the vehicle-injected positive controls. In addition, exosomes from P-Epi significantly reduced transforming growth factor-β (TGF-β)-induced expressions of type I collagen and fibronectin in 3T3 fibroblast cells. Collectively, culture supernatant of P-Epi has preventive effects on PF, thus cell therapy is not necessarily required. Further exploration of substances secreted by P-Epi and their protective mechanisms could lead to the development of therapeutic strategies to limit PF., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objectives: The impact of positive peritoneal cytology has been a matter of controversy in early-stage endometrial cancer for several years. The latest staging systems do not take into consideration its presence; however, emerging evidence about its potential harmful effect on patient survival outcomes suggests otherwise. In the present systematic review and meta-analysis, we sought to accumulate current evidence. Materials and Methods: Medline, Scopus, the Cochrane Central Register of Controlled Trials CENTRAL, Google Scholar and Clinicaltrials.gov databases were searched for relevant articles. Effect sizes were calculated in Rstudio using the meta function. A sensitivity analysis was carried out to evaluate the possibility of small-study effects and p-hacking. Trial sequential analysis was used to evaluate the adequacy of the sample size. The methodological quality of the included studies was assessed using the Newcastle-Ottawa scale. Results: Fifteen articles were finally included in the present systematic review that involved 19,255 women with early-stage endometrial cancer. The Newcastle-Ottawa scale indicated that the majority of included studies had a moderate risk of bias in their selection of participants, a moderate risk of bias in terms of the comparability of groups (positive peritoneal cytology vs. negative peritoneal cytology) and a low risk of bias concerning the assessment of the outcome. The results of the meta-analysis indicated that women with early-stage endometrial cancer and positive peritoneal cytology had significantly lower 5-year recurrence-free survival (RFS) (hazards ratio (HR) 0.26, 95% CI 0.09, 0.71). As a result of the decreased recurrence-free survival, patients with positive peritoneal cytology also exhibited reduced 5-year overall survival outcomes (HR 0.50, 95% CI 0.27, 0.92). The overall survival of the included patients was considerably higher among those that did not have positive peritoneal cytology (HR 12.76, 95% CI 2.78, 58.51). Conclusions: Positive peritoneal cytology seems to be a negative prognostic indicator of survival outcomes of patients with endometrial cancer. Considering the absence of data related to the molecular profile of patients, further research is needed to evaluate if this factor should be reinstituted in future staging systems.

Introduction: Cell-free nucleic acids (cf-NAs) represent a promising biomarker of various pathological and physiological conditions. Since its discovery in 1948, cf-NAs gained prognostic value in oncology, immunology, and other relevant fields. In peritoneal dialysis (PD), blood purification is performed by exposing the peritoneal membrane. Relevant sections: Complications of PD such as acute peritonitis and peritoneal membrane aging are often critical in PD patient management. In this review, we focused on bacterial DNA, cell-free DNA, mitochondrial DNA (mtDNA), microRNA (miRNA), and their potential uses as biomarkers for monitoring PD and its complications. For instance, the isolation of bacterial DNA in early acute peritonitis allows bacterial identification and subsequent therapy implementation. Cell-free DNA in peritoneal dialysis effluent (PDE) represents a marker of stress of the peritoneal membrane in both acute and chronic PD complications. Moreover, miRNA are promising hallmarks of peritoneal membrane remodeling and aging, even before its manifestation. In this scenario, with multiple cytokines involved, mtDNA could be considered equally meaningful to determine tissue inflammation., Conclusions: This review explores the relevance of cf-NAs in PD, demonstrating its promising role for both diagnosis and treatment. Further studies are necessary to implement the use of cf-NAs in PD clinical practice.