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1.
Medicine (Baltimore) ; 99(23): e20444, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32501991

RESUMO

This study aimed to compare the quality of virtual low-keV monoenergetic images vs conventional images reconstructed from dual-layer spectral detector computed tomography (SDCT) for the detection of peritoneal implants of ovarian cancer.Fifty ovarian cancer patients who underwent abdominopelvic SDCT scans were included in this retrospective study. Virtual monoenergetic images at 40 (VMI40) and 50 keV (VMI50), and two conventional images were reconstructed using filtered back projection (FBP) and iterative model reconstruction (IMR) protocols. The mean attenuation of the peritoneal implant, signal-to-noise ratio (SNR), contrast-to-noise ratio relative to ascites (CNRA) and adjacent reference tissues (e.g., bowel wall, hepatic, or splenic parenchyma [CNRB]) were calculated and compared using paired t tests. Qualitative image analysis regarding overall image quality, image noise, image blurring, lesion conspicuity, was performed by two radiologists. A subgroup analysis according to the peritoneal implant region was also conducted.VMI40 yielded significantly higher mean attenuation (183.35) of SNR and CNR values (SNR 11.69, CNRA 7.39, CNRB 2.68), compared to VMI50, IR, and FBP images (P < .001). The mean attenuation (129.65), SNR and CNR values (SNR 9.37, CNRA 5.72, CNRB 2.02) of VMI50 were also significantly higher than those of IR and FBP images (P < .001). In the subgroup analysis, all values were significantly higher on VMI40 regardless of the peritoneal implant region (P < .05). In both readers, overall image quality and image blurring showed highest score in VMI50, while image noise and lesion conspicuity showed best score in IMR and VMI40 respectively. Inter-reader agreements are moderate to almost perfect in every parameter.The low-keV VMIs improved both quantitative assessment and lesion conspicuity of peritoneal implants from ovarian cancer compared to conventional images.


Assuntos
Neoplasias Ovarianas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/epidemiologia , Peritônio/efeitos dos fármacos , Pesquisa Qualitativa , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , República da Coreia/epidemiologia , Estudos Retrospectivos
2.
Khirurgiia (Mosk) ; (6): 24-30, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32573528

RESUMO

OBJECTIVE: To study and systematize clinical symptoms of tuberculous perivisceritis, to clarify diagnostic value of laboratory and instrumental survey in these patients and to identify the features of surgical treatment. MATERIAL AND METHODS: There were 8 patients with tuberculous perivisceritis. Examination included computed tomography of the abdominal cavity and chest, ultrasound, laparoscopy. All patients underwent surgical treatment with histological, cytological, microbiological and molecular genetic analysis of peritoneal exudate and biopsy of peritoneal specimens. RESULTS: Clinical picture of tuberculous perivisceritis is variable and non-specific. Periods of exacerbation are replaced by periods of prolonged remission. The complex of radiological survey used in verification of perivisceritis does not allow accurate determining the nature of disease. However, peritoneal tuberculosis may be suspected as a rule considering signs of thickening of the peritoneum. Objective confirmation of perivisceritis is possible only during surgical intervention. In this case, etiological factor can be established only after a thorough histological examination of resected fibrous capsule. CONCLUSION: Clinical picture of tuberculous perivisceritis does not have specific symptoms. The disease is characterized by prolonged and undulating course. Acute peritonitis and acute intestinal obstruction may be suspected during exacerbation of the pathological process. Laparotomy followed by complete excision of fibrous capsule and adhesiolysis is preferred.


Assuntos
Peritônio/cirurgia , Peritonite Tuberculosa/diagnóstico , Peritonite Tuberculosa/cirurgia , Aderências Teciduais/cirurgia , Doença Aguda , Fibrose/microbiologia , Fibrose/cirurgia , Humanos , Obstrução Intestinal/etiologia , Peritônio/microbiologia , Peritônio/patologia , Aderências Teciduais/microbiologia
3.
Medicine (Baltimore) ; 99(21): e20447, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481347

RESUMO

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


Assuntos
Doenças Cardiovasculares/mortalidade , Soluções para Diálise/efeitos adversos , Glucose/metabolismo , Diálise Peritoneal/mortalidade , Adulto , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Estudos de Coortes , Soluções para Diálise/uso terapêutico , Feminino , Humanos , Análise de Classes Latentes , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/métodos , Peritônio/fisiopatologia , Sistema de Registros/estatística & dados numéricos , Fatores de Tempo
4.
J Surg Oncol ; 122(1): 85-95, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32436240

RESUMO

Over the past decade, there has been a considerable increase in the utilization of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the management of patients with peritoneal metastases. This is due to improved safety and favorable oncologic outcomes, including curative potential. CRS/HIPEC has a steep learning curve and requires familiarity with peritonectomy procedures. This review will outline the technical aspects and learning curve of CRS/HIPEC.


Assuntos
Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Humanos , Curva de Aprendizado , Peritônio/cirurgia
5.
Khirurgiia (Mosk) ; (3): 29-34, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32271734

RESUMO

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


Assuntos
Materiais Biocompatíveis/efeitos adversos , Heparina/administração & dosagem , Poliésteres/administração & dosagem , Polipropilenos/efeitos adversos , Suturas/efeitos adversos , Aderências Teciduais/prevenção & controle , Animais , Materiais Biocompatíveis/administração & dosagem , Materiais Revestidos Biocompatíveis/administração & dosagem , Materiais Revestidos Biocompatíveis/efeitos adversos , Modelos Animais de Doenças , Heparina/efeitos adversos , Masculino , Neovascularização Patológica/etiologia , Neovascularização Patológica/prevenção & controle , Peritônio/irrigação sanguínea , Peritônio/patologia , Peritônio/cirurgia , Poliésteres/efeitos adversos , Polipropilenos/administração & dosagem , Ratos , Ratos Wistar , Aderências Teciduais/etiologia , Aderências Teciduais/patologia
6.
BMC Infect Dis ; 20(1): 239, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32197582

RESUMO

BACKGROUND: Peritoneal tuberculosis is the most common cause of low albumin gradient ascites in developing countries, but it can be easily confused with other causes of ascites. Peritoneal tuberculosis requires early recognition of symptoms and signs in order to make a quick diagnosis for appropriate treatment. Measurement of adenosine deaminase (ADA) level > 39 in ascites fluid is an established test to diagnose peritoneal tuberculosis. Many low-income countries do not currently test for adenosine deaminase in ascites fluid, including Rwanda. METHOD: Cross-sectional, descriptive study conducted through the Internal Medicine Department of three university teaching hospitals in Rwanda. Participants were patients older than 16 years presenting to tertiary referral hospitals with ascites of unknown cause. RESULTS: Of 103 ascites fluid samples collected, 52 of them (50.5%) had an elevated ADA, consistent with a presumptive diagnosis of peritoneal TB. Among those 52 subjects diagnosed with peritoneal TB, 39 out of 52 (75%) did not receive anti-TB medications. Among the 17 subjects who were treated with anti-TB medications, 4 of 17 (23.6%) did not have peritoneal TB based on ADA level. Samples with low-albumin gradient ascites were more likely to have high ADA ≥39 IU/L (p = 0.039). CONCLUSION: Our findings suggest that 3out of 4 patients with PTB in Rwanda are not getting TB treatment and 1 in 4 patients who are taking TB medications do not need it. Even if the true number of Rwandans who are being undertreated and overtreated is less than our study suggests, these results should prompt a larger study of peritoneal tuberculosis. Adding adenosine deaminase (ADA) to the diagnostic tools available to clinicians could help achieve the goal of correctly putting every Rwandan with tuberculosis on treatment, while avoiding unnecessary tuberculosis medications in those who do not have the disease.


Assuntos
Adenosina Desaminase/análise , Ascite/diagnóstico , Peritonite Tuberculosa/diagnóstico , Peritonite Tuberculosa/epidemiologia , Adulto , Líquido Ascítico/enzimologia , Ensaios Enzimáticos Clínicos , Estudos Transversais , Países em Desenvolvimento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Peritônio/microbiologia , Peritonite Tuberculosa/microbiologia , Prevalência , Ruanda/epidemiologia
7.
FASEB J ; 34(1): 1558-1575, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914688

RESUMO

Endometriosis is a chronic inflammatory, gynecological disease characterized by the presence of endometrial-like tissue lesions outside of the uterus. Neutrophils are elevated in the systemic circulation and peritoneal fluid of endometriosis patients; however, whether and how neutrophils contribute to endometriosis pathophysiology remain poorly understood. With emerging roles for neutrophils in chronic and sterile inflammatory conditions, we sought to provide in-depth characterization of neutrophil involvement in endometriosis. We demonstrate that neutrophils reside within patient endometriotic lesions and that patient lesions possess a microenvironment that may influence neutrophil recruitment and function. We also provide the first evidence that systemic circulating neutrophils from endometriosis patients display distinct transcriptomic differences compared neutrophils from healthy control subjects. Time course characterization of our syngeneic, immunocompetent mouse model of endometriosis revealed that neutrophils are rapidly recruited to the peritoneal environment early after endometriotic lesion establishment and remain present in murine lesions long term. In vivo neutrophil depletion altered the systemic and peritoneal immune microenvironment of mice with endometriosis as demonstrated by changes in pro-inflammatory and angiogenic mediators. Taken together, these findings highlight a novel role for neutrophils in early events such as angiogenesis and modulation of the local inflammatory environment associated with endometriosis pathogenesis.


Assuntos
Endometriose/patologia , Endométrio/patologia , Neutrófilos/patologia , Animais , Modelos Animais de Doenças , Feminino , Humanos , Inflamação/patologia , Camundongos , Neovascularização Patológica/patologia , Infiltração de Neutrófilos/fisiologia , Peritônio/patologia
8.
Am J Physiol Renal Physiol ; 318(2): F457-F467, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31760768

RESUMO

As an electrophilic nitroalkene fatty acid, nitro-oleic acid (OA-NO2) exerts multiple biological effects that contribute to anti-inflammation, anti-oxidative stress, and antiapoptosis. However, little is known about the role of OA-NO2 in peritoneal fibrosis. Thus, in the present study, we examined the effects of OA-NO2 on the high glucose (HG)-induced epithelial-mesenchymal transition (EMT) in human peritoneal mesothelial cells (HPMCs) and evaluated the morphological and immunohistochemical changes in a rat model of peritoneal dialysis-related peritoneal fibrosis. In in vitro experiments, we found that HG reduced the expression level of E-cadherin and increased Snail, N-cadherin, and α-smooth muscle actin expression levels in HPMCs. The above-mentioned changes were attenuated by pretreatment with OA-NO2. Additionally, OA-NO2 also inhibited HG-induced activation of the transforming growth factor-ß1/Smad signaling pathway and NF-κB signaling pathway. Meanwhile, OA-NO2 inhibited HG-induced phosphorylation of Erk and JNK. The results from the in vivo experiments showed that OA-NO2 notably relieved peritoneal fibrosis by decreasing the thickness of the peritoneum; it also inhibited expression of transforming growth factor-ß1, α-smooth muscle actin, N-cadherin, and vimentin and enhanced expression of E-cadherin in the peritoneum. Collectively, these results suggest that OA-NO2 inhibits the HG-induced epithelial-mesenchymal transition in HPMCs and attenuates peritoneal dialysis-related peritoneal fibrosis.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glucose , Ácidos Oleicos/farmacologia , Diálise Peritoneal , Fibrose Peritoneal/prevenção & controle , Peritônio/efeitos dos fármacos , Actinas/metabolismo , Animais , Antígenos CD/metabolismo , Caderinas/metabolismo , Linhagem Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fibrose Peritoneal/metabolismo , Fibrose Peritoneal/patologia , Peritônio/metabolismo , Peritônio/patologia , Ratos Wistar , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismo , Vimentina/metabolismo
9.
Am J Physiol Renal Physiol ; 318(1): F229-F237, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31760769

RESUMO

Long-term peritoneal dialysis (PD) is associated with functional and structural alterations of the peritoneal membrane. Inflammation may be the key moment, and, consequently, fibrosis may be the end result of chronic inflammatory reaction. The objective of the present study was to identify genes involved in peritoneal alterations during PD by comparing the transcriptome of peritoneal cells in patients with short- and long-term PD. Peritoneal effluent of the long dwell of patients with stable PD was centrifuged to obtain peritoneal cells. The gene expression profiles of peritoneal cells using microarray between patients with short- and long-term PD were compared. Based on microarray analysis, 31 genes for quantitative RT-PCR validation were chosen. A 4-h peritoneal equilibration test was performed on the day after the long dwell. Transport parameters and protein appearance rates were assessed. Genes involved in the immune system process, immune response, cell activation, and leukocyte and lymphocyte activation were found to be substantially upregulated in the long-term group. Quantitative RT-PCR validation showed higher expression of CD24, lymphocyte antigen 9 (LY9), TNF factor receptor superfamily member 4 (TNFRSF4), Ig associated-α (CD79A), chemokine (C-C motif) receptor 7 (CCR7), carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), and IL-2 receptor-α (IL2RA) in patients with long-term PD, with CD24 having the best discrimination ability between short- and long-term treatment. A relationship between CD24 expression and genes for collagen and matrix formation was shown. Activation of CD24 provoked by pseudohypoxia due to extremely high glucose concentrations in dialysis solutions might play the key role in the development of peritoneal membrane alterations.


Assuntos
Nefropatias/terapia , Diálise Peritoneal , Peritônio/metabolismo , Transcriptoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Regulação da Expressão Gênica , Humanos , Nefropatias/genética , Nefropatias/metabolismo , Masculino , Pessoa de Meia-Idade
10.
Virchows Arch ; 476(2): 219-230, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31616981

RESUMO

Clinical significance of the pT4 category in colon cancer is increasing with several therapeutic implications. The aim of this study was to evaluate variability in diagnosing pT4a colon cancer. Twelve pathologists classified 66 preselected scanned Hematoxylin/Eosin-stained slides with tumor cells at a distance of 25-1500 µm (n = 22), 0-25 µm (n = 22), or on (n = 22) the peritoneal surface. Inter- and intraobserver variability were calculated using Kappa statistics. For interlaboratory variability, pathology reports of pT3 and pT4a colon cancer were extracted from the Dutch Pathology Registry between 2012 and 2015. The proportion of pT4a (pT4a/(pT3+pT4a)) was compared between 33 laboratories. Potential risk of understaging was assessed by determining the average number of blocks taken from pT3 and pT4a N0-2M0 tumors with metachronous peritoneal metastasis. Interobserver variability among 12 pathologists was 0.50 (95%CI 0.41-0.60; moderate agreement). Intraobserver variability (8 pathologists) was 0.71 (substantial agreement). A total of 7745 reports with pT3 or pT4aN0-2M0 colon cancer from 33 laboratories were included for interlaboratory analysis. Median percentage of pT4a was 15.5% (range 3.2-24.6%). After adjustment for case mix, 8 labs diagnosed pT4a significantly less or more frequently than the median lab. Metachronous peritoneal metastases were histologically verified in 170 of 6629 pT3 and in 129 of 1116 pT4a tumors, with a mean number of blocks of 4.03(SD 1.51) and 4.78 (SD 1.76) taken from the primary tumors, respectively (p < 0.001). A substantial variability in diagnosing pT4a colon cancer exists, both at pathologist and laboratory level. Diagnosis of pT4a stage appears to be challenging and there is a need for standardizing assessment of this pathological entity.


Assuntos
Adenocarcinoma/patologia , Neoplasias do Colo/patologia , Metástase Linfática/patologia , Peritônio/patologia , Adenocarcinoma/diagnóstico , Neoplasias do Colo/diagnóstico , Humanos , Invasividade Neoplásica/patologia , Variações Dependentes do Observador , Prognóstico , Estudos Retrospectivos
12.
Am J Physiol Renal Physiol ; 318(2): F338-F353, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31841386

RESUMO

IL-6 is a vital inflammatory factor in the peritoneal cavity of patients undergoing peritoneal dialysis (PD). The present study examined the effect of IL-6 trans-signaling on structural alterations of the peritoneal membrane. We investigated whether the epithelial-to-mesenchymal transition (EMT) process of human peritoneal mesothelial cells (HPMCs) and the production of proangiogenic factors were controlled by IL-6 trans-signaling. Its role in the peritoneal alterations was detected in a mouse model. The morphology of HPMCs and levels of cytokines in PD effluent were also explored. Stimulation of HPMCs with the IL-6 and soluble IL-6 receptor complex (IL-6/S) promoted the EMT process of HPMCs depending on the STAT3 pathway. In a coculture system of HPMCs and human umbilical vein endothelial cells, IL-6/S mediated the production of VEGF and angiopoietins so as to downregulate the expression of endothelial junction molecules and finally affect vascular permeability. Daily intraperitoneal injection of high glucose-based dialysis fluid induced peritoneal fibrosis, angiogenesis, and macrophage infiltration in a mouse model, accompanied by phosphorylation of STAT3. Blockade of IL-6 trans-signaling prevented these peritoneum alterations. The fibroblast-like appearance of HPMCs ex vivo was upregulated in patients undergoing prevalent PD accompanied by increasing levels of IL-6, VEGF, and angiopoietin-2 in the PD effluent. Taken together, these findings identified a critical link between IL-6 trans-signaling and structural alterations of the peritoneal membrane, and it might be a potential target for the treatment of patients undergoing PD who have developed peritoneal alterations.


Assuntos
Comunicação Celular , Células Endoteliais da Veia Umbilical Humana/metabolismo , Interleucina-6/metabolismo , Fibrose Peritoneal/metabolismo , Peritônio/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteínas Angiogênicas/metabolismo , Animais , Permeabilidade Capilar , Células Cultivadas , Receptor gp130 de Citocina/metabolismo , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Masculino , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica , Diálise Peritoneal , Fibrose Peritoneal/etiologia , Fibrose Peritoneal/patologia , Peritônio/patologia , Fosforilação , Transdução de Sinais
13.
J Pathol ; 250(1): 55-66, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31579932

RESUMO

Peritoneal fibrosis remains a problem in kidney failure patients treated with peritoneal dialysis. Severe peritoneal fibrosis with encapsulation or encapsulating peritoneal sclerosis is devastating and life-threatening. Although submesothelial fibroblasts as the major precursor of scar-producing myofibroblasts in animal models and M2 macrophage (Mϕ)-derived chemokines in peritoneal effluents of patients before diagnosis of encapsulating peritoneal sclerosis have been identified, attenuation of peritoneal fibrosis is an unmet medical need partly because the mechanism for cross talk between Mϕs and fibroblasts remains unclear. We use a sodium hypochlorite-induced mouse model akin to clinical encapsulated peritoneal sclerosis to study how the peritoneal Mϕs activate fibroblasts and fibrosis. Sodium hypochlorite induces the disappearance of CD11bhigh F4/80high resident Mϕs but accumulation of CD11bint F4/80int inflammatory Mϕs (InfMϕs) through recruiting blood monocytes and activating local cell proliferation. InfMϕs switch to express chemokine (C-C motif) ligand 17 (CCL17), CCL22, and arginase-1 from day 2 after hypochlorite injury. More than 75% of InfMϕs undergo genetic recombination by Csf1r-driven Cre recombinase, providing the possibility to reduce myofibroblasts and fibrosis by diphtheria toxin-induced Mϕ ablation from day 2 after injury. Furthermore, administration of antibody against CCL17 can reduce Mϕs, myofibroblasts, fibrosis, and improve peritoneal function after injury. Mechanistically, CCL17 stimulates migration and collagen production of submesothelial fibroblasts in culture. By breeding mice that are induced to express red fluorescent protein in Mϕs and green fluorescence protein (GFP) in Col1a1-expressing cells, we confirmed that Mϕs do not produce collagen in peritoneum before and after injury. However, small numbers of fibrocytes are found in fibrotic peritoneum of chimeric mice with bone marrow from Col1a1-GFP reporter mice, but they do not contribute to myofibroblasts. These data demonstrate that InfMϕs switch to pro-fibrotic phenotype and activate peritoneal fibroblasts through CCL17 after injury. CCL17 blockade in patients with peritoneal fibrosis may provide a novel therapy. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Quimiocina CCL17/metabolismo , Fibroblastos/metabolismo , Mediadores da Inflamação/metabolismo , Ativação de Macrófagos , Macrófagos Peritoneais/metabolismo , Comunicação Parácrina , Fibrose Peritoneal/metabolismo , Peritônio/metabolismo , Animais , Proliferação de Células , Quimiocina CCL17/genética , Colágeno Tipo I/genética , Modelos Animais de Doenças , Fibroblastos/patologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Macrófagos Peritoneais/patologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fibrose Peritoneal/induzido quimicamente , Fibrose Peritoneal/genética , Fibrose Peritoneal/patologia , Peritônio/patologia , Fenótipo , Regiões Promotoras Genéticas , Transdução de Sinais , Hipoclorito de Sódio
14.
J Pathol ; 250(1): 79-94, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31579944

RESUMO

Dysregulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the pathogenesis of many cancers. However, the role of EZH2 in peritoneal fibrosis remains unknown. We investigated EZH2 expression in peritoneal dialysis (PD) patients and assessed its role in peritoneal fibrosis in cultured human peritoneal mesothelial cells (HPMCs) and murine models of peritoneal fibrosis induced by chlorhexidine gluconate (CG) or high glucose peritoneal dialysis fluid (PDF) by using 3-deazaneplanocin A (3-DZNeP), and EZH2 conditional knockout mice. An abundance of EZH2 was detected in the peritoneum of patients with PD associated peritonitis and the dialysis effluent of long-term PD patients, which was positively correlated with expression of TGF-ß1, vascular endothelial growth factor, and IL-6. EZH2 was found highly expressed in the peritoneum of mice following injury by CG or PDF. In both mouse models, treatment with 3-DZNeP attenuated peritoneal fibrosis and inhibited activation of several profibrotic signaling pathways, including TGF-ß1/Smad3, Notch1, epidermal growth factor receptor and Src. EZH2 inhibition also inhibited STAT3 and nuclear factor-κB phosphorylation, and reduced lymphocyte and macrophage infiltration and angiogenesis in the injured peritoneum. 3-DZNeP effectively improved high glucose PDF-associated peritoneal dysfunction by decreasing the dialysate-to-plasma ratio of blood urea nitrogen and increasing the ratio of dialysate glucose at 2 h after PDF injection to initial dialysate glucose. Moreover, delayed administration of 3-DZNeP inhibited peritoneal fibrosis progression, reversed established peritoneal fibrosis and reduced expression of tissue inhibitor of metalloproteinase 2, and matrix metalloproteinase-2 and -9. Finally, EZH2-KO mice exhibited less peritoneal fibrosis than EZH2-WT mice. In HPMCs, treatment with EZH2 siRNA or 3-DZNeP suppressed TGF-ß1-induced upregulation of α-SMA and Collagen I and preserved E-cadherin. These results indicate that EZH2 is a key epigenetic regulator that promotes peritoneal fibrosis. Targeting EZH2 may have the potential to prevent and treat peritoneal fibrosis. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Adenosina/análogos & derivados , Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Fibrose Peritoneal/prevenção & controle , Peritônio/efeitos dos fármacos , Interferência de RNA , RNA Interferente Pequeno/genética , Adenosina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neovascularização Patológica , Fibrose Peritoneal/genética , Fibrose Peritoneal/metabolismo , Fibrose Peritoneal/patologia , Peritônio/metabolismo , Peritônio/patologia , RNA Interferente Pequeno/metabolismo , Transdução de Sinais
15.
Carbohydr Polym ; 229: 115552, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31826495

RESUMO

The complications from surgery associated peritoneal adhesion can be alleviated by combination of physical isolation and pharmaceutical treatment. This work aims to develop thermo-sensitive hydrogel barrier by combining mitomycin C (MMC) with modified tempo oxidized nanocellulose (cTOCN) through EDC/NHS-chemical conjugation followed by integration with methyl cellulose (MC). The MMC was successfully combined with cTOCN and ensured controlled release of MMC from hydrogel throughout 14 days. Amount of MC (1.5, 2.5, 3.5% w/v) was proportional to gelation time and inversely proportional to degradation of hydrogel. The optimized hydrogel (C2.5T1M0.2) needed only 30 s for thermoreversible sol-gel (4℃-37℃) phenomenon and did not show in vitro fibroblast cells toxicity as well as ensured complete adhesion prevention efficacy, reperitonealization in rat side wall-cecal abrasion model. Overall, the developed C2.5T1M0.2 thermo-gel advances state-of-the-art in view of cytocompatibility, mechanical stability, optimum degradation, good injectability, sustain drug release from surgical sites, and satisfactory de novo anti-adhesion capacity.


Assuntos
Celulose/química , Hidrogéis/química , Mitomicina/química , Peritônio/patologia , Aderências Teciduais/prevenção & controle , Animais , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Força Compressiva , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Camundongos , Mitomicina/metabolismo , Mitomicina/uso terapêutico , Ratos , Ratos Sprague-Dawley , Reologia , Temperatura , Viscosidade
16.
Ren Fail ; 42(1): 1-9, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31826694

RESUMO

Background: Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis (PD), with high morbidity and mortality that requires an early diagnosis for effective treatment. PD withdrawal and bacterial peritonitis are important triggers for the onset of EPS. However, few studies have focused on cases of PD withdrawal without a clinical diagnosis of peritonitis, cirrhosis, or carcinomatosis. We aimed to compare the clinical characteristics and computed tomography (CT) images of patients with or without ascites in such situations and assess clinical outcomes in terms of mortality.Methods: Our retrospective review included 78 patients who withdraw PD between January 2000 and December 2017.Results: Ten patients had ascites, and 68 did not have a significant intra-abdominal collection. The ascites group had a significantly longer PD duration (months; 134.41 [range, 35.43-181.80] vs. 32.42 [733-183.47], p < 0.001) and higher peritoneal membrane transport status based on the dialysate-to-plasma ratios of creatinine (0.78 ± 0.08 vs. 0.68 ± 0.11, p = 0.009) and glucose (0.27 ± 0.07 vs. 0.636 ± 0.08, p = 0.001) than the control group. CT parameters, including peritoneal calcification, thickness, bowel tethering, or bowel dilatation, were not all present in each patient with ascites and EPS. During the 12-month study period, the ascites group had a higher risk for developing EPS (70% vs. 0%, p < 0.001) and a higher 12-month all-cause mortality (30% vs. 0%, p = 0.002).Conclusions: Ascites accumulation was not rare after PD discontinuation. A longer PD duration and high peritoneal membrane transport status could predict subsequent ascites accumulation. Furthermore, patients with ascites were at a higher risk of EPS.


Assuntos
Ascite/epidemiologia , Falência Renal Crônica/terapia , Diálise Peritoneal/efeitos adversos , Fibrose Peritoneal/epidemiologia , Peritonite/epidemiologia , Adulto , Idoso , Ascite/diagnóstico , Ascite/etiologia , Creatinina/sangue , Creatinina/metabolismo , Soluções para Diálise , Feminino , Seguimentos , Humanos , Falência Renal Crônica/sangue , Masculino , Pessoa de Meia-Idade , Fibrose Peritoneal/diagnóstico , Fibrose Peritoneal/etiologia , Fibrose Peritoneal/patologia , Peritônio/diagnóstico por imagem , Peritônio/metabolismo , Peritônio/patologia , Peritonite/diagnóstico , Peritonite/etiologia , Peritonite/patologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X , Suspensão de Tratamento
17.
Drug Deliv ; 27(1): 40-53, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31858848

RESUMO

Albumin is a remarkable carrier protein with multiple cellular receptor and ligand binding sites, which are able to bind and transport numerous endogenous and exogenous compounds. The development of albumin-bound drugs is gaining increased importance in the targeted delivery of cancer therapy. Intraperitoneal (IP) drug delivery represents an attractive strategy for the local treatment of peritoneal metastasis (PM). PM is characterized by the presence of widespread metastatic tumor nodules on the peritoneum, mostly originating from gastro-intestinal or gynaecological cancers. Albumin as a carrier for chemotherapy holds considerable promise for IP delivery in patients with PM. Data from recent (pre)clinical trials suggest that IP albumin-bound chemotherapy may result in superior efficacy in the treatment of PM compared to standard chemotherapy formulations. Here, we review the evidence on albumin-bound chemotherapy with a focus on IP administration and its efficacy in PM.


Assuntos
Albuminas/administração & dosagem , Antineoplásicos/administração & dosagem , Portadores de Fármacos/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Transporte Biológico , Relação Dose-Resposta a Droga , Humanos , Injeções Intraperitoneais , Nanopartículas/química , Neoplasias Peritoneais/patologia , Peritônio/anatomia & histologia , Peritônio/patologia , Ligação Proteica/fisiologia
18.
J Matern Fetal Neonatal Med ; 33(4): 657-663, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29996688

RESUMO

Objective: We compared the extraperitoneal cesarean section to transperitoneal cesarean on fetal delivery time.Material and methods: This randomized study included 210 pregnant women undergoing cesarean section for elective reasons, repeat cesarean (< four), or dystocia. Patients who required an urgent cesarean section, who were at high risk for obstetric or maternal bleeding, who had a uterine or adnexal mass, or who requested tubal ligation were excluded from the study. The primary outcome of the study was the skin incision-to-delivery time. The sample size was set to detect of 1-minute difference in fetal delivery time between groups (two-tailed hypothesis, α = 0.05, ß = 0.10). Secondary outcome measures were total operation time, intraoperative nausea, gag reflex, vomiting, pain and anxiety for those receiving regional anesthesia, postoperative pain, change in hemoglobin, postoperative analgesic requirements, nausea, vomiting and shoulder pain, urogenital distress, time until gas passage, and neonatal outcome.Results: No significant difference occurred between the two groups for skin incision-to- delivery time (extraperitoneal cesarean 3.9 minutes [2.1-7.3] versus transperitoneal cesarean 4.2 minutes [1.9-8.2], p = .065). Significant differences regarding intraoperative pain, total operation time, postoperative pain at the surgical site and shoulder pain, analgesic requirements, time until gas passage, and oral tolerability favored the extraperitoneal group. No significant differences between groups occurred regarding other seconder outcome parameters.Conclusions: There is no clinically significant difference between extraperitoneal cesarean section and transperitoneal cesarean on fetal delivery time. Extraperitoneal cesarean reduces postoperative pain, analgesic requirements, and improves oral tolerability.


Assuntos
Cesárea/métodos , Duração da Cirurgia , Peritônio/cirurgia , Adulto , Cesárea/estatística & dados numéricos , Feminino , Humanos , Gravidez , Adulto Jovem
19.
Am J Surg ; 219(1): 58-64, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30982572

RESUMO

BACKGROUND: Peritoneal cancer index (PCI) is an important prognostic factor in colorectal cancer peritoneal metastases (CRPM), however it fails to consider the time period over which disease burden develops. The volume-time index (VTI) is the ratio between PCI and time from primary tumour resection. METHODS: A retrospective cohort study of 182 patients managed from 1996 to 2017 was performed. RESULTS: As stratified by high vs low VTI groups, median overall survival (OS) was 23 months (95% 17-46) vs 44 months (95% 35-72) with a difference in 5-year OS of 20.3% (95%CI 10.2-40.4) vs 40.1% (95%CI 29.7-54.1), p = 0.002. No difference in 5-year recurrence free survival (RFS) exists. On multivariable analysis, an elevated VTI was independently associated with poorer OS (adjusted HR 3.20, 95%CI 1.64-6.23, p < 0.001) and RFS (adjusted HR 1.90, 95%CI 1.10-3.29, p = 0.02). CONCLUSION: VTI is an independent prognostic factor for OS and RFs in patients with CRPM undergoing CRS/IPC, behaving as a surrogate of tumour aggressiveness.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Adulto , Idoso , Antineoplásicos/administração & dosagem , Estudos de Coortes , Neoplasias Colorretais/terapia , Procedimentos Cirúrgicos de Citorredução , Vias de Administração de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Peritônio , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Carga Tumoral
20.
Int J Nanomedicine ; 14: 9665-9675, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824158

RESUMO

Purpose: Vitamin D is a novel potential therapeutic agent for peritoneal dialysis (PD)-related peritoneal fibrosis, but it can induce hypercalcemia and vascular calcification, which limits its applicability. In this study, we create nanotechnology-based drug delivery systems to investigate its therapeutics and side effects. Materials and methods: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [amino-(polyethylene glycol)2000] (DSPE-PEG) and L-α-phosphatidylcholine (PC), which packages with 1α,25(OH)2D3, were used to construct vitamin D nanoliposomes. To confirm the function and safety of vitamin D nanoliposomes, peritoneal mesothelial cells were treated with TGF-ß1 and the reverse was attempted using vitamin D nanoliposomes. Antibodies (Ab) against the peritoneum-glycoprotein M6A (GPM6A) Ab were conjugated with vitamin D nanoliposomes. These particles were implanted into mice by intraperitoneal injection and the animals were monitored for the distribution and side effects induced by vitamin D. Results: Vitamin D nanoliposomes were taken up by the mesothelial cells over time without cell toxicity and it also provided the same therapeutic effect in vitro. In vivo study, fluorescent imaging showed vitamin D nanoliposomes allow specific peritoneum target effect and also ameliorate vitamin D side effect. Conclusion: Nanoliposomes vitamin D delivery systems for the prevention of PD-related peritoneal damage may be a potential clinical strategy in the future.


Assuntos
Nanomedicina , Diálise Peritoneal/efeitos adversos , Peritônio/patologia , Vitamina D/farmacologia , Animais , Anticorpos/farmacologia , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Liberação Controlada de Fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Cinética , Lipossomos , Camundongos , Nanopartículas/química , Nanopartículas/ultraestrutura , Peritônio/efeitos dos fármacos , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Fator de Crescimento Transformador beta1/metabolismo
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