Asunto(s)

Anastomosis Quirúrgica , Cirujanos , Humanos , Drenaje , Resultado del Tratamiento , Recto/cirugía , Colon/cirugía , Adhesión a Directriz , Peritoneo/cirugía

RESUMEN

Maintaining patients' temperature during surgery is beneficial since hypothermia has been linked with perioperative complications. Laparoscopic surgery involves the insufflation of carbon dioxide (CO2) into the peritoneal cavity and has become the standard in many surgical indications since it is associated with better and faster recovery. However, the use of cold and dry CO2 insufflation can lead to perioperative hypothermia. We aimed to assess the difference between intraperitoneal and core temperatures during laparoscopic surgery and evaluate the influence of duration and CO2 insufflation volume by fitting a mixed generalized additive model. In this prospective observational single-center cohort trial, we included patients aged over 17 with American Society of Anesthesiology risk scores I to III undergoing laparoscopic surgery. Anesthesia, ventilation, and analgesia followed standard protocols, while patients received active warming using blankets and warmed fluids. Temperature data, CO2 ventilation parameters, and intraabdominal pressure were collected. We recruited 51 patients. The core temperature was maintained above 36 °C and progressively raised toward 37 °C as pneumoperitoneum time passed. In contrast, the intraperitoneal temperature decreased, thus creating a widening difference from 0.4 [25th-75th percentile: 0.2-0.8] °C at the beginning to 2.3 [2.1-2.3] °C after 240 min. Pneumoperitoneum duration and CO2 insufflation volume significantly increased this temperature difference (P < 0.001 for both parameters). Core vs. intraperitoneal temperature difference increased linearly by 0.01 T °C per minute of pneumoperitoneum time up to 120 min and then 0.05 T °C per minute. Each insufflated liter per unit of time, i.e. every 10 min, increased the temperature difference by approximately 0.009 T °C. Our findings highlight the impact of pneumoperitoneum duration and CO2 insufflation volume on the difference between core and intraperitoneal temperatures. Implementing adequate external warming during laparoscopic surgery effectively maintains core temperature despite the use of dry and unwarmed CO2 gases, but peritoneal hypothermia remains a concern, suggesting the importance of further research into regional effects.Trial registration: Clinicaltrials.gov: NCT04294758.

Asunto(s)

Temperatura Corporal , Dióxido de Carbono , Laparoscopía , Humanos , Laparoscopía/métodos , Femenino , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Peritoneo/cirugía , Hipotermia/prevención & control , Hipotermia/etiología , Adulto , Insuflación/métodos , Neumoperitoneo Artificial/métodos , Cavidad Peritoneal/cirugía

RESUMEN

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.

Asunto(s)

Inflamación , Macrófagos , Diálisis Peritoneal , Fibrosis Peritoneal , Proteínas Quinasas p38 Activadas por Mitógenos , Animales , Humanos , Masculino , Ratones , Clorhexidina/análogos & derivados , Clorhexidina/farmacología , Inflamación/patología , Inflamación/metabolismo , Inflamación/genética , Lipopolisacáridos , Macrófagos/metabolismo , Ratones Noqueados , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Diálisis Peritoneal/efectos adversos , Fibrosis Peritoneal/metabolismo , Fibrosis Peritoneal/genética , Fibrosis Peritoneal/etiología , Fibrosis Peritoneal/patología , Peritoneo/patología , Células RAW 264.7

Asunto(s)

Laparoscopía , Pancreatectomía , Peritoneo , Grado de Desobstrucción Vascular , Humanos , Laparoscopía/métodos , Pancreatectomía/métodos , Peritoneo/cirugía , Neoplasias Pancreáticas/cirugía , Trasplante Autólogo/métodos , Masculino , Femenino , Vena Porta/cirugía , Procedimientos de Cirugía Plástica/métodos , Persona de Mediana Edad , Procedimientos Quirúrgicos Vasculares/métodos

RESUMEN

BACKGROUND/AIMS: Lemons (Citrus limon ) contain various nutrients and are among the most popular citrus fruit. Besides their antioxidant, anticancer, antibacterial, and anti-inflammatory properties, clinical studies have indicated their anti-allergic properties. METHODS: Using the differential-interference contrast (DIC) microscopy, we examined the effects of lemon juice and peel constituents, such as citric acid, ascorbic acid, hesperetin and eriodictyol, on the degranulation from rat peritoneal mast cells. Using fluorescence imaging with a water-soluble dye, Lucifer Yellow, we also examined their effects on the deformation of the plasma membrane. RESULTS: Lemon juice dose-dependently decreased the number of degranulated mast cells. At concentrations equal to or higher than 0.25 mM, citric acid, hesperetin, and eriodictyol significantly reduced the number of degranulating mast cells in a dose-dependent manner, while ascorbic acid required much higher doses to exert significant effects. At 1 mM, citric acid, hesperetin, and eriodictyol almost completely inhibited exocytosis and washed out the Lucifer Yellow trapped on the mast cell surface, while ascorbic acid did not. CONCLUSION: This study provides in vitro evidence for the first time that lemon constituents, such as citric acid, hesperetin, and eriodictyol, potently exert mast cell-stabilizing properties. These properties are attributable to their inhibitory effects on plasma membrane deformation in degranulating mast cells.

Asunto(s)

Ácido Ascórbico , Citrus , Flavanonas , Hesperidina , Mastocitos , Animales , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Citrus/química , Ratas , Ácido Ascórbico/farmacología , Masculino , Hesperidina/farmacología , Hesperidina/química , Flavanonas/farmacología , Flavanonas/química , Ácido Cítrico/farmacología , Ácido Cítrico/química , Degranulación de la Célula/efectos de los fármacos , Jugos de Frutas y Vegetales/análisis , Peritoneo/citología , Ratas Sprague-Dawley , Exocitosis/efectos de los fármacos , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Frutas/química , Isoquinolinas

RESUMEN

Gallbladder cancer (GBC) is a rare disease with a poor prognosis. Simple cholecystectomy may be an adequate treatment only for very early disease (Tis, T1a), whereas reoperation is recommended for more advanced disease (T1b and T2). Radical cholecystectomy should have two fundamental objectives: To radically resect the liver parenchyma and to achieve adequate clearance of the lymph nodes. However, recent studies have shown that compared with lymph node dissection alone, liver resection does not improve survival outcomes. The oncological roles of lymphadenectomy and liver resection is distinct. Therefore, for patients with incidental GBC without liver invasion, hepatic resection is not always mandatory.

Asunto(s)

Colecistectomía , Neoplasias de la Vesícula Biliar , Hepatectomía , Escisión del Ganglio Linfático , Humanos , Colecistectomía/efectos adversos , Colecistectomía/métodos , Neoplasias de la Vesícula Biliar/cirugía , Neoplasias de la Vesícula Biliar/patología , Hepatectomía/métodos , Hepatectomía/efectos adversos , Hallazgos Incidentales , Hígado/cirugía , Hígado/patología , Hígado/diagnóstico por imagen , Escisión del Ganglio Linfático/métodos , Escisión del Ganglio Linfático/efectos adversos , Metástasis Linfática , Estadificación de Neoplasias , Peritoneo/cirugía , Peritoneo/patología , Resultado del Tratamiento

RESUMEN

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.

Asunto(s)

Glicocálix , Lectinas , Glicocálix/metabolismo , Animales , Ratones , Lectinas/metabolismo , Epitelio/metabolismo , Humanos , Peritoneo/metabolismo , Peritoneo/patología , Femenino , Coloración y Etiquetado/métodos , Epiplón/metabolismo , Epiplón/patología

RESUMEN

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 TIM4hi MHCIIlo residential macrophages and the influx of increased Ly6C+ monocytes and TIM4lo MHCIIhi macrophages. The recruitment of MHCIIhi inflammatory macrophages was extensive in Mac Gata6 KO mice due to the severe disappearance of TIM4hi MHCIIlo residential macrophages. Ki67 expression confirmed GATA6-dependent proliferative ability, showing different proliferative phenotypes of TIM4+ residential macrophages in Gata6f/f and Mac Gata6 KO mice. Peritoneal proinflammatory cytokines were elevated after lesion induction. When cytokine levels were compared between Gata6f/f and Mac Gata6 KO mice, TNFα at day 21 in Gata6f/f mice was higher than in Mac Gata6 KO mice. Lesion induction increased both abdominal and hind paw sensitivities. Gata6f/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 Gata6f/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.

Asunto(s)

Endometriosis , Factor de Transcripción GATA6 , Macrófagos Peritoneales , Animales , Femenino , Ratones , Citocinas/metabolismo , Modelos Animales de Enfermedad , Endometriosis/inmunología , Endometriosis/patología , Endometriosis/metabolismo , Ganglios Espinales/metabolismo , Ganglios Espinales/inmunología , Factor de Transcripción GATA6/metabolismo , Factor de Transcripción GATA6/genética , Hiperalgesia/etiología , Hiperalgesia/metabolismo , Hiperalgesia/inmunología , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Peritoneo/patología , Peritoneo/inmunología , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/genética

RESUMEN

We present the trial-and-error process of standardizing robot-assisted radical nephroureterectomy (RANU) at a high-volume center in Japan. Our urology team performed 53 RANU cases using the Da Vinci Xi system, undergoing five major evolutionary stages. We performed RANU via transperitoneal approach in all cases and lymph-node dissection in selected cases. During the evolution, we adopted a lithotomy position and significantly modified port placement to facilitate lower ureter management. However, we ultimately arrived at a method that minimizes port and patient repositioning during lower ureter processing. By strategically placing ProGrasp™ forceps in the most caudal port, we effectively retracted the bladder and grasped the opened bladder wall during lower ureter manipulation. This approach also allowed us to perform pelvic, para-aortic, and renal portal lymph-node dissection without major changes in patient positioning or port placement. Nevertheless, we acknowledge that some variations in positioning and techniques may be necessary depending on specific case requirements.

Asunto(s)

Escisión del Ganglio Linfático , Nefroureterectomía , Procedimientos Quirúrgicos Robotizados , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hospitales de Alto Volumen , Japón , Escisión del Ganglio Linfático/métodos , Nefroureterectomía/métodos , Posicionamiento del Paciente/métodos , Peritoneo/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/normas , Uréter/cirugía

RESUMEN

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.

Asunto(s)

Transición Epitelial-Mesenquimal , Glucosa , Glucólisis , MicroARNs , Diálisis Peritoneal , Fibrosis Peritoneal , Peritoneo , Factor de Transcripción STAT3 , MicroARNs/metabolismo , MicroARNs/genética , Factor de Transcripción STAT3/metabolismo , Humanos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Glucosa/metabolismo , Glucosa/farmacología , Glucólisis/efectos de los fármacos , Diálisis Peritoneal/efectos adversos , Fibrosis Peritoneal/metabolismo , Fibrosis Peritoneal/patología , Fibrosis Peritoneal/etiología , Fibrosis Peritoneal/genética , Peritoneo/patología , Peritoneo/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Línea Celular , Regulación hacia Abajo , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos

RESUMEN

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.

Asunto(s)

Enfermedades Peritoneales , Peritoneo , Humanos , Peritoneo/diagnóstico por imagen , Peritoneo/patología , Peritoneo/anatomía & histología , Enfermedades Peritoneales/diagnóstico por imagen , Diagnóstico Diferencial

RESUMEN

BACKGROUND: Urinary Dickkopf 3 (DKK3) excretion is a recently established biomarker of renal functional development. Its excretion into the peritoneal cavity has not been reported. We here studied DKK3 in peritoneal dialysis. METHODS: DKK3 was assessed in serum, urine and dialysate in a prevalent adult peritoneal dialysis cohort and its concentration analyzed in relation to creatinine and clinical characteristics. RESULTS: Highest DKK3 concentrations were found in serum, followed by urine. Dialysate concentrations were significantly lower. Dialysate DKK3 correlated with both other compartments. Serum, dialysate and urine values were stable during three months of follow-up. Continuous ambulatory dialysis (CAPD) but not cycler-assisted peritoneal dialysis (CCPD) volume-dependently increased peritoneal DKK3 in relation to creatinine. RAAS blockade significantly decreased urinary, but not serum or peritoneal DKK3. CONCLUSION: Our data provide a detailed characterization of DKK3 in peritoneal dialysis. They support the notion that the RAAS system is essential for renal DKK3 handling.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales , Diálisis Peritoneal , Humanos , Masculino , Femenino , Persona de Mediana Edad , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Quimiocinas/sangre , Quimiocinas/metabolismo , Anciano , Adulto , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Fallo Renal Crónico/terapia , Fallo Renal Crónico/metabolismo , Biomarcadores/sangre , Soluciones para Diálisis/metabolismo , Riñón/metabolismo , Peritoneo/metabolismo , Diálisis Peritoneal Ambulatoria Continua , Sistema Renina-Angiotensina/fisiología , Creatinina/orina , Creatinina/sangre , Creatinina/metabolismo

RESUMEN

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-ß1 (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-ß1 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-ß1 increased the expression of TGFßRI, p-Smad3, p-PDGFRß and p-EGFR, while treatment with LCZ696 abrogated the activation of TGF-ß/Smad3, PDGFRß 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-ß1 secretion from M2 macrophages. CONCLUSION: Our study demonstrated that LCZ696 improves PF and ameliorates TGF-ß1-induced EMT of HPMCs by blocking TGF-ß/Smad3, PDGFRß and EGFR pathways. Meanwhile, LCZ696 also inhibits M2 macrophage polarization by regulating STAT6 pathway.

Asunto(s)

Antagonistas de Receptores de Angiotensina , Compuestos de Bifenilo , Transición Epitelial-Mesenquimal , Macrófagos , Fibrosis Peritoneal , Tetrazoles , Valsartán , Transición Epitelial-Mesenquimal/efectos de los fármacos , Ratones , Animales , Valsartán/farmacología , Compuestos de Bifenilo/farmacología , Antagonistas de Receptores de Angiotensina/farmacología , Fibrosis Peritoneal/metabolismo , Fibrosis Peritoneal/patología , Fibrosis Peritoneal/prevención & control , Humanos , Tetrazoles/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Aminobutiratos/farmacología , Células RAW 264.7 , Modelos Animales de Enfermedad , Combinación de Medicamentos , Neprilisina/antagonistas & inhibidores , Neprilisina/metabolismo , Masculino , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Transcripción STAT6/metabolismo , Peritoneo/patología , Peritoneo/citología , Peritoneo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos C57BL

RESUMEN

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)-ß and vascular endothelial growth factor (VEGF)-A are the key mediators of fibrosis and angiogenesis, respectively. Bioincompatible factors of PD fluid upregulate TGF-ß expression by mesothelial cells that contributes to the development of fibrosis. Angiogenesis and lymphangiogenesis can progress during fibrosis via TGF-ß-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.

Asunto(s)

Diálisis Peritoneal , Fibrosis Peritoneal , Peritoneo , Humanos , Diálisis Peritoneal/efectos adversos , Fibrosis Peritoneal/etiología , Fibrosis Peritoneal/patología , Fibrosis Peritoneal/metabolismo , Peritoneo/patología , Peritoneo/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Animales , Neovascularización Patológica , Factor A de Crecimiento Endotelial Vascular/metabolismo , Peritonitis/etiología , Peritonitis/patología , Peritonitis/metabolismo

RESUMEN

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 α5ß1 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.

Asunto(s)

Ascitis , Fibrina , Fibrinógeno , Integrina alfa5beta1 , Neoplasias Ováricas , Esferoides Celulares , Microambiente Tumoral , Humanos , Femenino , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Ascitis/patología , Ascitis/metabolismo , Integrina alfa5beta1/metabolismo , Esferoides Celulares/metabolismo , Esferoides Celulares/patología , Fibrinógeno/metabolismo , Fibrina/metabolismo , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/metabolismo , Neoplasias Peritoneales/patología , Carcinoma Epitelial de Ovario/metabolismo , Carcinoma Epitelial de Ovario/patología , Línea Celular Tumoral , Receptores de Vitronectina/metabolismo , Proteína de Unión al GTP rac1/metabolismo , Adhesión Celular , Peritoneo/patología , Peritoneo/metabolismo , Epitelio/metabolismo , Epitelio/patología , Cadherinas/metabolismo , Células Tumorales Cultivadas

RESUMEN

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.

Asunto(s)

Receptores de Hialuranos , Diálisis Peritoneal , Fibrosis Peritoneal , Peritoneo , Transducción de Señal , Fibrosis Peritoneal/metabolismo , Fibrosis Peritoneal/etiología , Fibrosis Peritoneal/patología , Animales , Ratones , Receptores de Hialuranos/metabolismo , Humanos , Peritoneo/patología , Peritoneo/metabolismo , Diálisis Peritoneal/efectos adversos , Modelos Animales de Enfermedad , Inflamación/metabolismo , Presión/efectos adversos , Masculino , Proliferación Celular , Transición Epitelial-Mesenquimal , Ratones Endogámicos C57BL , Línea Celular , Movimiento Celular

RESUMEN

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 Wt1CreERT2-tdTnu 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-ß1 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: EFNBhigh 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.

Asunto(s)

Comunicación Celular , Vesículas Extracelulares , Linfangiogénesis , Animales , Ratones , Vesículas Extracelulares/metabolismo , Humanos , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/metabolismo , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/genética , Macrófagos/metabolismo , Macrófagos/patología , Peritoneo/patología , Peritoneo/metabolismo , Línea Celular Tumoral , Técnicas de Cocultivo , Transducción de Señal

RESUMEN

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.

Asunto(s)

Modelos Animales de Enfermedad , Enfermedades Peritoneales , Ratas Sprague-Dawley , Animales , Adherencias Tisulares/patología , Adherencias Tisulares/etiología , Masculino , Ratas , Enfermedades Peritoneales/patología , Enfermedades Peritoneales/etiología , Ciego/cirugía , Ciego/patología , Ciego/lesiones , Distribución Aleatoria , Técnicas de Sutura , Peritoneo/patología , Peritoneo/lesiones , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/patología

RESUMEN

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.

Asunto(s)

Compuestos de Bencidrilo , Senescencia Celular , Transición Epitelial-Mesenquimal , Glucósidos , Diálisis Peritoneal , Fibrosis Peritoneal , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Animales , Transición Epitelial-Mesenquimal/efectos de los fármacos , Glucósidos/farmacología , Compuestos de Bencidrilo/farmacología , Diálisis Peritoneal/efectos adversos , Senescencia Celular/efectos de los fármacos , Masculino , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Fibrosis Peritoneal/patología , Fibrosis Peritoneal/metabolismo , Fibrosis Peritoneal/prevención & control , Peritoneo/patología , Peritoneo/efectos de los fármacos , Peritoneo/metabolismo , Ratones , Modelos Animales de Enfermedad , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Glucosa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ratones Endogámicos C57BL , Células Cultivadas , Daño del ADN/efectos de los fármacos

RESUMEN

PURPOSE: Single-Port Robot-Assisted Partial Nephrectomy (SP-RAPN) can be performed by transperitoneal and retroperitoneal approaches. However, there is a lack of surgical outcomes for novel Retroperitoneal Low Anterior Access (LAA) in SP-RAPN. The study compared outcomes of the standard approach (SA), considering transperitoneal (TP) and posterior retroperitoneal (RP) access vs LAA in SP-RAPN series. METHODS: 102 consecutive patients underwent SP-RAPN between 2019 and 2023 at a tertiary referral robotic center were identified. Baseline characteristics, peri- and post-operative outcomes were collected. Patients were stratified according to surgical approach into standard (RP or TP) vs LAA and, subsequently, RP vs LAA. Multivariable logistic regression analysis was used to test the probability of the same-day discharge adjusting for comorbidity indexes. RESULTS: Overall, 102 consecutive patients were included in this study (68 SA - 26 TP and 42 posterior RP vs 34 LAA). Median age was 60 (IQR 51.5-66) years and median BMI was 31 (IQR 26.3-37.6). No baseline differences were observed. LAA exhibited significantly shorter length of stay (LOS) (median 10 [IQR 8-12] vs 24 [IQR 12-30.2.] hours, p < .0001), reduced post-operative pain (p < .0001) and decreased narcotic use on 0-1 PO Day (p < .001) compared to SA and RP only. Multivariate analysis, adjusting for comorbidities, identified LAA as a strong predictor for Same-Day Discharge. CONCLUSION: LAA is an effective approach as well as RP and TP, regardless of the renal mass location, whether it is anterior or posterior, upper/mid or lower pole, yielding favorable outcomes in LOS, post-operative pain and decreased narcotics use compared to SA in SP-RAPN.

Asunto(s)

Nefrectomía , Procedimientos Quirúrgicos Robotizados , Humanos , Nefrectomía/métodos , Persona de Mediana Edad , Masculino , Femenino , Procedimientos Quirúrgicos Robotizados/métodos , Anciano , Espacio Retroperitoneal , Resultado del Tratamiento , Estudios Retrospectivos , Peritoneo/cirugía , Neoplasias Renales/cirugía