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1.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(7): 629-633, 2020 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-32683821

RESUMO

Membrane anatomy is the anatomy of mesentery in broad sense and its beds, which was merged from clinical results of surgical practice, optic observation and traditional theories contradiction or omission. Membrane anatomy is not only a plane, but also a body or bloc which is surrounded by fascia and serous membrane. It is not only fascia, but also a channel or pathway, in which the life event occurred. It is not only mesentery anatomy, but included mesentery beds, on which the mesentery was lied, even buried in. Following the new version of this anatomy map, surgical hazard during operation and postoperative oncological recurrence will be decreased simultaneously. And, following the definition of the mesentery in broad sense, new mesenteries will be discovered under macro surgery, which will optimize surgical operation and get better surgical and oncological results.


Assuntos
Fáscia/anatomia & histologia , Mesentério/anatomia & histologia , Fáscia/patologia , Humanos , Mesentério/patologia , Mesentério/cirurgia , Peritônio/anatomia & histologia , Peritônio/patologia , Peritônio/cirurgia
2.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(7): 643-647, 2020 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-32683823

RESUMO

The theory of membrane anatomy is now widely accepted due to the observation of fine anatomical structure with the help of laparoscopic magnifying effect. From the perspective of systematic anatomy, the mesentery is considered as an integral organ in the theory of mesenteric anatomy. Interfascial anatomy belongs to regional anatomy, which focuses on the guiding significance of fascial space for operation. The theory of membrane anatomy belongs to surgical anatomy or applied anatomy, which emphasizes the anatomy of membrane and mesangial bed, and reveals the existence of 'metastasis V' in the mesentery. It is considered that the essence of membrane anatomy operation is to prevent cancer leakage. Various theories of membrane anatomy seek common ground while reserving differences, complement each other, and upgrade iteratively. They help to explain the structure and function of membrane from different perspectives and they are of great benefit to improve the quality of operations. Thus, they should be treated in an eclectic manner.


Assuntos
Fáscia/anatomia & histologia , Mesentério/anatomia & histologia , Fáscia/patologia , Humanos , Laparoscopia , Mesentério/patologia , Mesentério/cirurgia , Modelos Biológicos , Metástase Neoplásica , Peritônio/anatomia & histologia , Peritônio/patologia , Peritônio/cirurgia
3.
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
4.
J Pathol ; 251(2): 175-186, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32232854

RESUMO

Neutrophil infiltration is a hallmark of peritoneal inflammation, but mechanisms regulating neutrophil recruitment in patients with peritoneal dialysis (PD)-related peritonitis are not fully defined. We examined 104 samples of PD effluent collected during acute peritonitis for correspondence between a broad range of soluble parameters and neutrophil counts. We observed an association between peritoneal IL-17 and neutrophil levels. This relationship was evident in effluent samples with low but not high IFN-γ levels, suggesting a differential effect of IFN-γ concentration on neutrophil infiltration. Surprisingly, there was no association of neutrophil numbers with the level of CXCL1, a key IL-17-induced neutrophil chemoattractant. We investigated therefore the production of CXCL1 by human peritoneal mesothelial cells (HPMCs) under in vitro conditions mimicking clinical peritonitis. Stimulation of HPMCs with IL-17 increased CXCL1 production through induction of transcription factor SP1 and activation of the SP1-binding region of the CXCL1 promoter. These effects were amplified by TNFα. In contrast, IFN-γ dose-dependently suppressed IL-17-induced SP1 activation and CXCL1 production through a transcriptional mechanism involving STAT1. The SP1-mediated induction of CXCL1 was also observed in HPMCs exposed to PD effluent collected during peritonitis and containing IL-17 and TNFα, but not IFN-γ. Supplementation of the effluent with IFN-γ led to a dose-dependent activation of STAT1 and a resultant inhibition of SP1-induced CXCL1 expression. Transmesothelial migration of neutrophils in vitro increased upon stimulation of HPMCs with IL-17 and was reduced by IFN-γ. In addition, HPMCs were capable of binding CXCL1 at their apical cell surface. These observations indicate that changes in relative peritoneal concentrations of IL-17 and IFN-γ can differently engage SP1-STAT1, impacting on mesothelial cell transcription of CXCL1, whose release and binding to HPMC surface may determine optimal neutrophil recruitment and retention during peritonitis. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.


Assuntos
Quimiocina CXCL1/metabolismo , Interferon gama/farmacologia , Interleucina-17/farmacologia , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Peritônio/efeitos dos fármacos , Peritonite/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Cultivadas , Quimiocina CXCL1/genética , Feminino , Humanos , Interferon gama/metabolismo , Interleucina-17/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Neutrófilos/patologia , Peritônio/metabolismo , Peritônio/patologia , Peritonite/genética , Peritonite/patologia , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais , Fator de Transcrição Sp1/genética , Transcrição Genética
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.
Brasília; CONITEC; mar. 2020.
Não convencional em Português | BRISA/RedTESA | ID: biblio-1122930

RESUMO

INTRODUÇÃO: A associação de cirurgia citorredutora e perfusão intraoperatória da cavidade peritoneal, com solução quimioterápica hipertérmica, representa uma nova e promissora modalidade terapêutica para o MPM. Sua incidência varia em todo o mundo, sendo as maiores taxas observadas na Austrália, Bélgica e Grã-Bretanha. O surgimento do MPM está associado à exposição ao amianto. Com longo período de latência (15 a 60 anos), é esperado aumento na incidência do MPM nas próximas décadas. Em países como o Brasil, também é esperado aumento na mortalidade por essa neoplasia nos próximos anos. PERGUNTA: O tratamento com cirurgia de citorredução com hipertermoquimioterapia é mais eficaz e custo-efetivo em pacientes com mesotelioma peritoneal difuso maligno quando comparado à quimioterapia sistêmica? TECNOLOGIA: Cirurgia de Citorredução (peritonectomia) com Quimioterapia Intraperitoneal Hipertérmica (HIPEC). EVIDÊNCIAS CIENTÍFICAS: Não foram encontrados ensaios clínicos sobre cirurgia de citorredução + HIPEC específicos para pacientes com MPM. Como a intervenção em questão é a HIPEC, estudos que utilizaram quimioterapia intraperitoneal normotérmica não foram considerados. Foram selecionados 11 estudos observacionais, que utilizaram bancos de dados de pacientes atendidos, em um ou mais centros de saúde. O número de pacientes avaliados nesses estudos variou de 11 a 401, e o período de coleta de dados de 3 a 26 anos. As técnicas de HIPEC utilizadas foram: em 4 estudos abdômen aberto (ou técnica do Coliseu); em outros 4 estudos abdômen fechado; em 2 estudos multicêntricos as abordagens cirúrgicas (aberta ou fechada) variaram entre os centros participantes e em um dos estudos detalhes da técnica não foram informados. A temperatura da HIPEC variou entre 40C e 43C, o tempo de administração da quimioterapia variou de 60 a 120 minutos, e a mitomicina c, associada ou não a outro medicamento (platina), foi utilizada na maioria dos estudos. A maioria dos estudos apresenta dados de sobrevida global em 5 anos, sendo observada uma variação entre 27% e 80,8%. AVALIAÇÃO ECONÔMICA: Foram simulados 24 pacientes em cadeia de Markov, com horizonte temporal da vida toda, sob a perspectiva do SUS utilizando uma taxa de desconto de 5%. A razão de custo efetividade incremental (ICER) do procedimento foi estimada em R$56.929,28/ano de vida ganho. Em nenhuma das simulações o valor foi estimado abaixo de 1 PIB per capita. Quando o valor da cirurgia é reduzido a R$34.621,00 o ICER é igual a esse limiar. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: A avaliação de impacto orçamentário estimou o valor incremental por centro de saúde assumindo que este realizaria 24 procedimentos por ano. Foi construído um modelo dinâmico de microssimulação com horizonte temporal de 5 anos. O parecer da SBCO estimou em 120-200 casos por ano de pseudomixoma peritoneal e mesotelioma peritoneal somados elegíveis para o procedimento. O resultado do impacto orçamentário médio anual para os 24 pacientes é R$ 1.692.864,36. Para toda a população, os valores por ano variaram de R$ 8.661.117,15 a R$ 14.657.044,06. RECOMENDAÇÃO PRELIMINAR: O Plenário da CONITEC realizado em 04 de dezembro de 2019, considerou que, apesar da evidência científica ser restrita, os resultados apontam para uma maior eficácia do tratamento com cirurgia de citorredução + HIPEC para os pacientes com mesotelioma peritoneal. A avaliação econômica encontrou uma razão de custoefetividade incremental com valor próximo a 2 PIB per capita por ano de vida ganho, o que foi considerado aceitável por se tratar de uma condição clínica rara. Portanto, emitiu-se recomendação preliminar pela incorporação no SUS da cirurgia de citorredução (peritonectomia) com Quimioterapia Intraperitoneal Hipertérmica (HIPEC), para tratamento de mesotelioma peritoneal. Essa incorporação deverá ser feita em centros de saúde com profissionais capacitados para realização, por se tratar de um procedimento complexo. CONSULTA PÚBLICA: Foram recebidas 45 contribuições técnico-científicas e 13 contribuições de experiência ou opinião, a grande maioria concordante com a recomendação preliminar da CONITEC a favor da incorporação da cirurgia de citorredução + HIPEC para o tratamento de mesotelioma peritoneal. Apenas uma contribuição não concorda, nem discorda da recomendação, mas relata não ter experiência com o tema. Não há argumentação que justifique a alteração da recomendação inicial. RECOMENDAÇÃO FINAL: Os membros da Conitec presentes na 86° reunião ordinária, nos dias 4 e 5 de março de 2020, deliberaram, por unanimidade, por recomendar a incorporação da cirurgia de citorredução + HIPEC para o tratamento de mesotelioma peritoneal, no SUS, conforme protocolo a ser elaborado pelo Ministério da Saúde. DECISÃO: incorporar a cirurgia de citorredução com hipertermoquimioterapia em pacientes com mesotelioma peritoneal maligno, conforme estabelecido pelo Ministério da Saúde, no âmbito do Sistema Único de Saúde - SUS, conforme a Portaria nº 12, publicada no Diário Oficial da União nº 64, seção 1, página 91, em 2 de abril de 2020.


Assuntos
Humanos , Peritônio/patologia , Quimioterapia Adjuvante/instrumentação , Procedimentos Cirúrgicos de Citorredução/instrumentação , Mesotelioma/cirurgia , Avaliação da Tecnologia Biomédica , Sistema Único de Saúde , Brasil , Análise Custo-Benefício/economia
7.
Clin Exp Metastasis ; 37(2): 325-332, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32002724

RESUMO

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) represents a novel approach to deliver intraperitoneal chemotherapy. We report our experience with PIPAC in patients with peritoneal metastasis (PM) from gastric cancer (GC). Data from GC patients (n = 20) included in the prospective PIPAC-OPC1 and PIPAC-OPC2 studies are reported. All patients had received prior systemic chemotherapy. The mean peritoneal cancer index (PCI) was 10.5 (range 0-39) and nine patients had diffuse GC. PIPAC with cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 were administered at 4-6-week intervals. Outcome criteria were objective tumour response, survival and adverse events. Twenty patients had 52 PIPAC procedures with a median follow-up of 10.4 months (3.3-26.5). Median survival from the time of PM diagnosis and after the first PIPAC procedure was 11.5 months and 4.7 months, respectively. Fourteen patients had repeated PIPAC (> 2), and the objective tumour response according to the histological peritoneal regression grading score (PRGS) was observed in 36%, whereas 36% had stable disease. Ten patients completed the three prescheduled sessions (per protocol group) and 40% of those displayed an objective tumour response, while 20% had stable disease. Only minor postoperative complications were noted, and none were considered causally related to the PIPAC treatment. PIPAC with low-dose cisplatin and doxorubicin can induce a quantifiable objective tumour response in selected patients with PM from GC. Survival data are encouraging and warrant further clinical studies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Peritônio/patologia , Neoplasias Gástricas/tratamento farmacológico , Administração Tópica , Adulto , Aerossóis , Idoso , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Peritônio/efeitos dos fármacos , Pressão , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Resultado do Tratamento
8.
Clin Exp Metastasis ; 37(2): 293-304, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32008138

RESUMO

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


Assuntos
Carcinoma Epitelial do Ovário/irrigação sanguínea , Microvasos/diagnóstico por imagem , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/irrigação sanguínea , Peritônio/patologia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma Epitelial do Ovário/secundário , Carcinoma Epitelial do Ovário/terapia , Hipóxia Celular , Quimioterapia Adjuvante , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/análise , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imageamento Tridimensional , Imuno-Histoquímica , Microvasos/patologia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Ovarianas/patologia , Ovariectomia , Ovário/patologia , Ovário/cirurgia , Neoplasias Peritoneais/prevenção & controle , Neoplasias Peritoneais/secundário , Peritônio/irrigação sanguínea , Estudos Prospectivos , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
Cancer Res ; 80(4): 843-856, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31911549

RESUMO

Among malignant mesotheliomas (MM), the sarcomatoid subtype is associated with higher chemoresistance and worst survival. Due to its low incidence, there has been little progress in the knowledge of the molecular mechanisms associated with sarcomatoid MM, which might help to define novel therapeutic targets. In this work, we show that loss of PTEN expression is frequent in human sarcomatoid MM and PTEN expression levels are lower in sarcomatoid MM than in the biphasic and epithelioid subtypes. Combined Pten and Trp53 deletion in mouse mesothelium led to nonepithelioid MM development. In Pten;Trp53-null mice developing MM, the Gαi2-coupled receptor subunit activated MEK/ERK and PI3K, resulting in aggressive, immune-suppressed tumors. Combined inhibition of MEK and p110ß/PI3K reduced mouse tumor cell growth in vitro. Therapeutic inhibition of MEK and p110ß/PI3K using selumetinib (AZD6244, ARRY-142886) and AZD8186, two drugs that are currently in clinical trials, increased the survival of Pten;Trp53-null mice without major toxicity. This drug combination effectively reduced the proliferation of primary cultures of human pleural (Pl) MM, implicating nonepithelioid histology and high vimentin, AKT1/2, and Gαi2 expression levels as predictive markers of response to combined MEK and p110ß/PI3K inhibition. Our findings provide a rationale for the use of selumetinib and AZD8186 in patients with MM with sarcomatoid features. This constitutes a novel targeted therapy for a poor prognosis and frequently chemoresistant group of patients with MM, for whom therapeutic options are currently lacking. SIGNIFICANCE: Mesothelioma is highly aggressive; its sarcomatoid variants have worse prognosis. Building on a genetic mouse model, a novel combination therapy is uncovered that is relevant to human tumors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Pleurais/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Compostos de Anilina/farmacologia , Compostos de Anilina/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzimidazóis/farmacologia , Benzimidazóis/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Cromonas/farmacologia , Cromonas/uso terapêutico , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Modelos Animais de Doenças , Epitélio/patologia , Feminino , Técnicas de Introdução de Genes , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mesotelioma/genética , Mesotelioma/patologia , Camundongos , Camundongos Knockout , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Terapia de Alvo Molecular/métodos , PTEN Fosfo-Hidrolase/genética , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Peritônio/patologia , Pleura/patologia , Neoplasias Pleurais/genética , Neoplasias Pleurais/patologia , Cultura Primária de Células , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Proteína Supressora de Tumor p53/genética
10.
Clin Nucl Med ; 45(4): 314-315, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31977494

RESUMO

On restaging FDG PET/CT for an 81-year-old man with oral cavity cancer, a large FDG-avid mesenteric mass suspicious for either metastasis or second primary was incidentally noted. Surgical pathology showed necrotizing granulomatous inflammation without evidence of tumor. All stains were negative for microorganisms. An elastin stain was negative as well, which excluded an origin of damaged blood vessels or vasculitis. The patient had no prior abdominal surgery or known gastrointestinal disease. Granuloma always poses a dilemma in the interpretation of PET/CT, due to its high FDG avidity and mass-like appearance which mimics neoplastic disease.


Assuntos
Granuloma/diagnóstico por imagem , Neoplasias Bucais/patologia , Neoplasias Peritoneais/secundário , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Fluordesoxiglucose F18 , Humanos , Masculino , Neoplasias Bucais/diagnóstico por imagem , Necrose , Neoplasias Peritoneais/diagnóstico por imagem , Peritônio/patologia , Compostos Radiofarmacêuticos
11.
Cancer Res ; 80(5): 1156-1170, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31932454

RESUMO

The noncanonical Wnt ligand Wnt5a is found in high concentrations in ascites of women with ovarian cancer. In this study, we elucidated the role of Wnt5a in ovarian cancer metastasis. Wnt5a promoted ovarian tumor cell adhesion to peritoneal mesothelial cells as well as migration and invasion, leading to colonization of peritoneal explants. Host components of the ovarian tumor microenvironment, notably peritoneal mesothelial cells and visceral adipose, secreted Wnt5a. Conditional knockout of host WNT5A significantly reduced peritoneal metastatic tumor burden. Tumors formed in WNT5A knockout mice had elevated cytotoxic T cells, increased M1 macrophages, and decreased M2 macrophages, indicating that host Wnt5a promotes an immunosuppressive microenvironment. The Src family kinase Fgr was identified as a downstream effector of Wnt5a. These results highlight a previously unreported role for host-expressed Wnt5a in ovarian cancer metastasis and suggest Fgr as a novel target for inhibition of ovarian cancer metastatic progression.Significance: This study establishes host-derived Wnt5a, expressed by peritoneal mesothelial cells and adipocytes, as a primary regulator of ovarian cancer intraperitoneal metastatic dissemination and identifies Fgr kinase as novel target for inhibition of metastasis.


Assuntos
Carcinoma Epitelial do Ovário/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/imunologia , Peritônio/patologia , Proteínas Proto-Oncogênicas/metabolismo , Proteína Wnt-5a/metabolismo , Quinases da Família src/metabolismo , Animais , Carcinoma Epitelial do Ovário/imunologia , Adesão Celular/imunologia , Linhagem Celular Tumoral , Movimento Celular/imunologia , Modelos Animais de Doenças , Células Epiteliais/imunologia , Células Epiteliais/patologia , Feminino , Técnicas de Silenciamento de Genes , Humanos , Macrófagos/imunologia , Camundongos , Camundongos Knockout , Metástase Neoplásica/imunologia , Metástase Neoplásica/patologia , Neoplasias Ovarianas/imunologia , Neoplasias Peritoneais/secundário , Peritônio/citologia , Peritônio/imunologia , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/imunologia , Microambiente Tumoral/imunologia , Proteína Wnt-5a/genética , Ensaios Antitumorais Modelo de Xenoenxerto
12.
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
13.
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
14.
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
15.
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
16.
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
17.
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
18.
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
19.
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
20.
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
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