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1.
Immunity ; 54(11): 2578-2594.e5, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34717795

RESUMO

Peritoneal immune cells reside unanchored within the peritoneal fluid in homeostasis. Here, we examined the mechanisms that control bacterial infection in the peritoneum using a mouse model of abdominal sepsis following intraperitoneal Escherichia coli infection. Whole-mount immunofluorescence and confocal microscopy of the peritoneal wall and omentum revealed that large peritoneal macrophages (LPMs) rapidly cleared bacteria and adhered to the mesothelium, forming multilayered cellular aggregates composed by sequentially recruited LPMs, B1 cells, neutrophils, and monocyte-derived cells (moCs). The formation of resident macrophage aggregates (resMφ-aggregates) required LPMs and thrombin-dependent fibrin polymerization. E. coli infection triggered LPM pyroptosis and release of inflammatory mediators. Resolution of these potentially inflammatory aggregates required LPM-mediated recruitment of moCs, which were essential for fibrinolysis-mediated resMφ-aggregate disaggregation and the prevention of peritoneal overt inflammation. Thus, resMφ-aggregates provide a physical scaffold that enables the efficient control of peritoneal infection, with implications for antimicrobial immunity in other body cavities, such as the pleural cavity or brain ventricles.


Assuntos
Infecções Bacterianas/etiologia , Infecções Bacterianas/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Cavidade Peritoneal/microbiologia , Animais , Biomarcadores , Microambiente Celular/imunologia , Modelos Animais de Doenças , Suscetibilidade a Doenças/imunologia , Mediadores da Inflamação/metabolismo , Camundongos , Peritonite/etiologia , Peritonite/metabolismo , Peritonite/patologia
2.
Immunity ; 52(4): 700-715.e6, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32294409

RESUMO

The omentum is a visceral adipose tissue rich in fat-associated lymphoid clusters (FALCs) that collects peritoneal contaminants and provides a first layer of immunological defense within the abdomen. Here, we investigated the mechanisms that mediate the capture of peritoneal contaminants during peritonitis. Single-cell RNA sequencing and spatial analysis of omental stromal cells revealed that the surface of FALCs were covered by CXCL1+ mesothelial cells, which we termed FALC cover cells. Blockade of CXCL1 inhibited the recruitment and aggregation of neutrophils at FALCs during zymosan-induced peritonitis. Inhibition of protein arginine deiminase 4, an enzyme important for the release of neutrophil extracellular traps, abolished neutrophil aggregation and the capture of peritoneal contaminants by omental FALCs. Analysis of omental samples from patients with acute appendicitis confirmed neutrophil recruitment and bacterial capture at FALCs. Thus, specialized omental mesothelial cells coordinate the recruitment and aggregation of neutrophils to capture peritoneal contaminants.


Assuntos
Apendicite/imunologia , Linfócitos/imunologia , Neutrófilos/imunologia , Omento/imunologia , Peritonite/imunologia , Células Estromais/imunologia , Doença Aguda , Animais , Apendicite/genética , Apendicite/microbiologia , Comunicação Celular/imunologia , Quimiocina CXCL1/genética , Quimiocina CXCL1/imunologia , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Epitélio/imunologia , Epitélio/microbiologia , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/patogenicidade , Armadilhas Extracelulares/imunologia , Feminino , Expressão Gênica , Humanos , Linfócitos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infiltração de Neutrófilos , Neutrófilos/microbiologia , Omento/microbiologia , Peritonite/induzido quimicamente , Peritonite/genética , Peritonite/microbiologia , Proteína-Arginina Desiminase do Tipo 4/genética , Proteína-Arginina Desiminase do Tipo 4/imunologia , Análise de Sequência de RNA , Análise de Célula Única , Células Estromais/microbiologia , Técnicas de Cultura de Tecidos , Zimosan/administração & dosagem
3.
Immunol Rev ; 324(1): 68-77, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38662554

RESUMO

The milky spots in omentum are atypical lymphoid tissues that play a pivotal role in regulating immune responses in the peritoneal cavity. The milky spots act as central hubs for collecting antigens and particles from the peritoneal cavity, regulating lymphocyte trafficking, promoting the differentiation and self-renewal of immune cells, and supporting the local germinal centre response. In addition, the milky spots exhibit unique developmental characteristics that combine the features of secondary and tertiary lymphoid tissues. These structures are innately programmed to form during foetal development; however, they can also be formed postnatally in response to peritoneal irritation such as inflammation, infection, obesity, or tumour metastasis. In this review, I discuss emerging perspectives on homeostatic development and organization of the milky spots.


Assuntos
Omento , Humanos , Animais , Omento/imunologia , Diferenciação Celular , Homeostase , Tecido Linfoide/imunologia , Centro Germinativo/imunologia , Cavidade Peritoneal
4.
Immunol Rev ; 324(1): 78-94, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38717136

RESUMO

It is now widely understood that visceral adipose tissue (VAT) is a highly active and dynamic organ, with many functions beyond lipid accumulation and storage. In this review, we discuss the immunological role of this tissue, underpinned by the presence of fat-associated lymphoid clusters (FALCs). FALC's distinctive structure and stromal cell composition support a very different immune cell mix to that found in classical secondary lymphoid organs, which underlies their unique functions of filtration, surveillance, innate-like immune responses, and adaptive immunity within the serous cavities. FALCs are important B cell hubs providing B1 cell-mediated frontline protection against infection and supporting B2 cell-adaptative immune responses. Beyond these beneficial immune responses orchestrated by FALCs, immune cells within VAT play important homeostatic role. Dysregulation of immune cells during obesity and aging leads to chronic pathological "metabolic inflammation", which contributes to the development of cardiometabolic diseases. Here, we examine the emerging and complex functions of B cells in VAT homeostasis and the metabolic complications of obesity, highlighting the potential role that FALCs play and emphasize the areas where further research is needed.


Assuntos
Linfócitos B , Homeostase , Gordura Intra-Abdominal , Humanos , Animais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Gordura Intra-Abdominal/imunologia , Gordura Intra-Abdominal/metabolismo , Obesidade/imunologia , Obesidade/metabolismo , Tecido Linfoide/imunologia , Tecido Linfoide/metabolismo , Imunidade Adaptativa
5.
Immunol Rev ; 324(1): 4-10, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38733141

RESUMO

Well known functions of adipose tissue include energy storage, regulation of thermogenesis, and glucose homeostasis-each of which are associated with the metabolic functions of fat. However, adipose tissues also have important immune functions. In this issue of Immunological Reviews, we present a series of articles that highlight the immune functions of adipose tissue, including the roles of specialized adipose-resident immune cells and fat-associated lymphoid structures. Importantly, immune cell functions in adipose tissues are often linked to the metabolic functions of adipocytes and vice versa. These reciprocal interactions and how they influence both immune and metabolic functions will be discussed in each article. In the first article, Wang et al.,11 discuss adipose-associated macrophages and how obesity and metabolism impact their phenotype and function. Several articles in this issue discuss T cells as either contributors to, or regulators of, inflammatory responses in adipose tissues. Valentine and Nikolajczyk12 provide insights into the role of T cells in obesity-associated inflammation and their contribution to metabolic dysfunction, whereas an article from Kallies and Vasanthakumar13 and another from Elkins and Li14 describe adipose-associated Tregs and how they help prevent inflammation and maintain metabolic homeostasis. Articles from Okabe35 as well as from Daley and Benezech15 discuss the structure and function of fat-associated lymphoid clusters (FALCs) that are prevalent in some adipose tissues and support local immune responses to pathogens, gut-derived microbes and fat-associated antigens. Finally, an article from Meher and McNamara16 describes how innate-like B1 cells in adipose tissues regulate cardiometabolic disease. Importantly, these articles highlight the physical and functional attributes of adipose tissues that are different between mice and humans, the metabolic and immune differences between various adipose depots in the body and the differences in immune cells, adipose tissues and metabolic functions between the sexes. At the end of this preface, we highlight how these differences are critically important for our understanding of anti-tumor immunity to cancers that metastasize to a specific example of visceral adipose tissue, the omentum. Together, these articles identify some unanswered mechanistic questions that will be important to address for a better understanding of immunity in adipose tissues.


Assuntos
Tecido Adiposo , Obesidade , Humanos , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Animais , Obesidade/imunologia , Obesidade/metabolismo , Homeostase , Inflamação/imunologia , Macrófagos/imunologia , Adipócitos/imunologia , Adipócitos/metabolismo , Metabolismo Energético , Imunidade
6.
Ann Surg Oncol ; 31(6): 3694-3704, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38530528

RESUMO

BACKGROUND: Vascularized gastroepiploic lymph node transfer (VGLNT) is a well-accepted surgical treatment for restoring physiological function in chronic lymphedema. However, the inclusion of substantial lymph nodes (LNs) in the flap remains uncertain. This study aimed to identify the anatomical basis for reliable flap harvest for VGLNT. PATIENTS AND METHODS: The anatomy of perigastric station 4d LNs was studied in healthy cadavers (n = 15) and patients with early gastric cancer (EGC) (n = 27). The omentum was divided into three segments: proximal, middle, and distal from the origin of the right gastroepiploic vessels. The flap dimension, number, location, size of LNs, and caliber of the vessels were reviewed. Eight patients underwent VGLNT for upper/lower limb lymphedema. RESULTS: The mean numbers of LNs in the proximal, middle, and distal segment were 2.5, 1.4, 0.5 in the cadavers, and 4.9, 2.7, 0.7 in the gastrectomy specimens, respectively. The proximal third included a significantly greater number of LNs than the distal third in the cadaveric (p = 0.024) and ECG (p = 0.016) specimens. A total of 95% of the LNs were located within proximal two-thirds of the flap from the vessel origin both in the cadavers (21.0 × 5.0 cm) and in the gastrectomy specimens (20 × 3.5 cm). In VGLNT, the transferred flap was 25.5 ± 6.9 × 4.1 + 0.7 cm in dimension, containing a mean number of 6.5 ± 1.9 LNs. At postoperative 6 months, the volumetric difference was significantly reduced by 22.8 ± 9.2% (p < 0.001). CONCLUSIONS: This study provides a distinct distribution pattern of station 4d LNs. Inclusion of the proximal two-thirds of the flap, which carries majority of the LNs, is recommended for VGLNT.


Assuntos
Cadáver , Gastrectomia , Linfonodos , Linfedema , Neoplasias Gástricas , Retalhos Cirúrgicos , Humanos , Linfonodos/cirurgia , Linfonodos/patologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Gastrectomia/métodos , Linfedema/cirurgia , Idoso , Artéria Gastroepiploica/cirurgia , Adulto , Prognóstico , Estudos de Casos e Controles , Seguimentos
7.
J Biomed Sci ; 31(1): 62, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862973

RESUMO

BACKGROUND: Ovarian carcinoma (OC) is a fatal malignancy, with most patients experiencing recurrence and resistance to chemotherapy. In contrast to hematogenous metastasizing tumors, ovarian cancer cells disseminate within the peritoneal cavity, especially the omentum. Previously, we reported omental crown-like structure (CLS) number is associated with poor prognosis of advanced-stage OC. CLS that have pathologic features of a dead or dying adipocyte was surrounded by several macrophages is well known a histologic hallmark for inflammatory adipose tissue. In this study, we attempted to clarify the interaction between metastatic ovarian cancer cells and omental CLS, and to formulate a therapeutic strategy for advanced-stage ovarian cancer. METHODS: A three-cell (including OC cells, adipocytes and macrophages) coculture model was established to mimic the omental tumor microenvironment (TME) of ovarian cancer. Caspase-1 activity, ATP and free fatty acids (FFA) levels were detected by commercial kits. An adipocyte organoid model was established to assess macrophages migration and infiltration. In vitro and in vivo experiments were performed for functional assays and therapeutic effect evaluations. Clinical OC tissue samples were collected for immunochemistry stain and statistics analysis. RESULTS: In three-cell coculture model, OC cells-derived IL-6 and IL-8 could induce the occurrence of pyroptosis in omental adipocytes. The pyroptotic adipocytes release ATP to increase macrophage infiltration, release FFA into TME, uptake by OC cells to increase chemoresistance. From OC tumor samples study, we demonstrated patients with high gasdermin D (GSDMD) expression in omental adipocytes is highly correlated with chemoresistance and poor outcome in advanced-stage OC. In animal model, by pyroptosis inhibitor, DSF, effectively retarded tumor growth and prolonged mice survival. CONCLUSIONS: Omental adipocyte pyroptosis may contribute the chemoresistance in advanced stage OC. Omental adipocytes could release FFA and ATP through the GSDMD-mediate pyroptosis to induce chemoresistance and macrophages infiltration resulting the poor prognosis in advanced-stage OC. Inhibition of adipocyte pyroptosis may be a potential therapeutic modality in advanced-stage OC with omentum metastasis.


Assuntos
Adipócitos , Resistencia a Medicamentos Antineoplásicos , Omento , Neoplasias Ovarianas , Piroptose , Microambiente Tumoral , Feminino , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Omento/metabolismo , Humanos , Adipócitos/metabolismo , Camundongos , Animais , Linhagem Celular Tumoral , Técnicas de Cocultura
8.
Cell Commun Signal ; 22(1): 443, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39285292

RESUMO

BACKGROUND: Epithelial ovarian cancer (EOC) is the deadliest gynaecological cancer with high mortality rates driven by the common development of resistance to chemotherapy. EOC frequently invades the omentum, an adipocyte-rich organ of the peritoneum and omental adipocytes have been implicated in promoting disease progression, metastasis and chemoresistance. The signalling mechanisms underpinning EOC omentum tropism have yet to be elucidated. METHODS: Three-dimensional co-culture models were used to explore adipocyte-EOC interactions. The impact of adipocytes on EOC proliferation, response to therapy and invasive capacity was assessed. Primary adipocytes and omental tissue were isolated from patients with ovarian malignancies and benign ovarian neoplasms. Exosomes were isolated from omentum tissue conditioned media and the effect of omentum-derived exosomes on EOC evaluated. Exosomal microRNA (miRNA) sequencing was used to identify miRNAs abundant in omental exosomes and EOC cells were transfected with highly abundant miRNAs miR-21, let-7b, miR-16 and miR-92a. RESULTS: We demonstrate the capacity of adipocytes to induce an invasive phenotype in EOC populations through driving epithelial-to-mesenchymal transition (EMT). Exosomes secreted by omental tissue of ovarian cancer patients, as well as patients without malignancies, induced proliferation, upregulated EMT markers and reduced response to paclitaxel therapy in EOC cell lines and HGSOC patient samples. Analysis of the omentum-derived exosomes from cancer patients revealed highly abundant miRNAs that included miR-21, let-7b, miR-16 and miR-92a that promoted cancer cell proliferation and protection from chemotherapy when transfected in ovarian cancer cells. CONCLUSIONS: These observations highlight the capacity of omental adipocytes to generate a pro-tumorigenic and chemoprotective microenvironment in ovarian cancer and other adipose-related malignancies.


Assuntos
Adipócitos , Exossomos , MicroRNAs , Invasividade Neoplásica , Neoplasias Ovarianas , Paclitaxel , Feminino , Exossomos/metabolismo , Humanos , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Adipócitos/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Omento/patologia , Omento/metabolismo , Proliferação de Células/efeitos dos fármacos , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/metabolismo , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/efeitos dos fármacos
9.
Surg Endosc ; 38(1): 97-104, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37917161

RESUMO

BACKGROUND: Radical gastrectomy is composed of gastrectomy, lymph node dissection, and omentectomy. Total omentectomy (TO) is expected to reduce the incidence of peritoneal recurrence. We aimed to investigate the necessity of TO for advanced gastric cancer (AGC) with serosal invasion. METHODS: We retrospectively reviewed 310 patients who underwent radical gastrectomy with TO and 93 patients who underwent partial omentectomy (PO) for gastric cancer with serosal invasion between August, 2005 and December, 2017. Finally, 91 patients in the PO group and 91 in the TO group were enrolled based on a 1:1 propensity-score matching analysis. We evaluated surgical and oncological outcomes, including 5-year overall and recurrence-free survival rates. RESULTS: There was no statistically significant difference between the two groups in postoperative complications. Recurrence sites showed similar patterns in both groups, including peritoneal recurrence (PO vs. TO, 18.7% vs. 28.6%; p = 0.188). Five-year overall survival was better in the PO group (p = 0.018), while 5-year recurrence-free survival was similar in both groups (p = 0.066). CONCLUSION: TO might not be an essential part of preventing peritoneal recurrence for AGC with serosal invasion. PO could be considered a radical gastrectomy for T4a gastric cancer.


Assuntos
Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Neoplasias Peritoneais/cirurgia , Neoplasias Gástricas/patologia , Peritônio/cirurgia , Peritônio/patologia , Membrana Serosa , Gastrectomia
10.
Surg Endosc ; 38(6): 3096-3105, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38622224

RESUMO

BACKGROUND: We performed a propensity score matched study comparing patients' short- and long-term results after laparoscopic omentum-preserving gastrectomy and open surgery with omentectomy with UICC stages 0-IV. METHODS: Between 2015 and 2022, 311 patients with gastric cancer underwent surgery at the University Clinical Centre Maribor. Of these, 249 met the inclusion criteria and 198 were included in the study group after PSM. RESULTS: Patients in both groups were well-balanced in demographic and pathological characteristics after PSM. There was no significant difference in the 5-year survival between groups (LAP: 62.2% vs. OPN: 54.4%; p = 0.950). The Cox regression model identified UICC stage and age as significant predictors for survival. In both groups, peritoneal dissemination was the most common site of recurrence. The multivariate analysis identified the UICC stage as a significant predictor for peritoneal recurrence, while omental preservation was not associated with a higher risk of peritoneal dissemination. Omentum preservation was not associated with more intestinal obstruction. Patients in the LAP group had significantly shorter hospital stays (LAP: 9(6) vs. OPN: 10(5); p = 0.009), less postoperative morbidity (LAP: 17% vs. OPN: 23.4%; p = 0.009), and significantly more extracted LNs per operation compared to open surgery (LAP: 31 ± 11 LNs vs. OPN: 25 ± 12 LNs; p = 0.002). CONCLUSION: Based on our results, we recommend the use of laparoscopic omentum-preserving gastrectomy in patients with early and advanced gastric cancer.


Assuntos
Gastrectomia , Laparoscopia , Estadiamento de Neoplasias , Omento , Pontuação de Propensão , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Omento/cirurgia , Gastrectomia/métodos , Feminino , Masculino , Laparoscopia/métodos , Laparoscopia/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Estudos Retrospectivos , Tratamentos com Preservação do Órgão/métodos , Tempo de Internação/estatística & dados numéricos , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Neoplasias Peritoneais/patologia , Recidiva Local de Neoplasia/epidemiologia
11.
World J Surg Oncol ; 22(1): 236, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39243034

RESUMO

BACKGROUND: The effect of omentum preservation (OP) on locally advanced gastric cancer (LAGC) remains controversial. This study aimed to investigate the long-term prognosis of LAGC patients with OP versus omentum resection (OR). METHODS: A comprehensive search of databases including PubMed, Web of Science, Embase, and Cochrane Library was conducted up until February 2024. Statistical analysis was performed using Stata 12.0 software. The primary outcome was to assess the impact of OP on the long-term prognosis of patients with LAGC, including overall survival (OS) and recurrence-free survival (RFS). RESULTS: A total of six case-control studies were included, encompassing a cohort of 1897 patients. The OP group consisted of 844 patients, while the OR group comprised 1053 patients. The study results showed that the OS (HR = 0.72, 95% CI: 0.58-0.90, P = 0.003) and 5-year RFS (HR = 0.79, 95% CI: 0.63-0.99, P = 0.038) in the OP group were superior to those observed in the OR group. Subgroup analysis indicated that 5-year OS (HR = 0.64, P = 0.003) and 5-year RFS (HR = 0.69, P = 0.005) in the OP group were also better than those in the OR group in Korea. However, the subgroup analysis conducted on stage T3-T4 tumors revealed no statistically significant differences in OS (P = 0.083) and 5-year RFS (P = 0.173) between the two groups. CONCLUSION: Compared with OR, OP shows non-inferiority in patients with LAGC and can be considered a potential treatment option for radical gastrectomy.


Assuntos
Gastrectomia , Omento , Neoplasias Gástricas , Humanos , Estudos de Casos e Controles , Gastrectomia/métodos , Omento/cirurgia , Omento/patologia , Tratamentos com Preservação do Órgão/métodos , Prognóstico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida
12.
Int J Mol Sci ; 25(11)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38891809

RESUMO

Pancreatic ductal adenocarcinoma (PDAC), characterized by hypovascularity, hypoxia, and desmoplastic stroma is one of the deadliest malignancies in humans, with a 5-year survival rate of only 7%. The anatomical location of the pancreas and lack of symptoms in patients with early onset of disease accounts for late diagnosis. Consequently, 85% of patients present with non-resectable, locally advanced, or advanced metastatic disease at diagnosis and rely on alternative therapies such as chemotherapy, immunotherapy, and others. The response to these therapies highly depends on the stage of disease at the start of therapy. It is, therefore, vital to consider the stages of PDAC models in preclinical studies when testing new therapeutics and treatment modalities. We report a standardized induction of cell-based orthotopic pancreatic cancer models in mice and the identification of vital features of their progression by ultrasound imaging and histological analysis of the level of pancreatic stellate cells, mature fibroblasts, and collagen. The results highlight that early-stage primary tumors are secluded in the pancreas and advance towards infiltrating the omentum at week 5-7 post implantation of the BxPC-3 and Panc-1 models investigated. Late stages show extensive growth, the infiltration of the omentum and/or stomach wall, metastases, augmented fibroblasts, and collagen levels. The findings can serve as suggestions for defining growth parameter-based stages of orthotopic pancreatic cancer models for the preclinical testing of drug efficacy in the future.


Assuntos
Carcinoma Ductal Pancreático , Modelos Animais de Doenças , Neoplasias Pancreáticas , Animais , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Camundongos , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Humanos , Linhagem Celular Tumoral
13.
Acta Chir Belg ; 124(2): 137-142, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37027318

RESUMO

Extragastrointestinal stromal tumors (EGISTs) are rare mesenchymal neoplasms, which develop in the retroperitoneum, mesentery, and omentum, lacking continuity to the stomach or intestines. Authors hereby present a female patient with a large heterogeneous abdominal mass as a case of an omental EGIST. A 46-year-old woman was referred to our hospital due to an insidious enlargement and colicky pain in the right iliac fossa. Abdominal palpation revealed a voluminous, freely mobile, and non-pulsatile mesoabdominal bulge expanding to the hypogastrium. On exploratory midline laparotomy, the tumor was densely fused to the greater omentum, not connected to the stomach, without gross involvement of adjacent structures. The large mass was completely excised after adequate mobilization. Immunohistochemical techniques showed strong and diffuse expression of WT1, actin and DOG-1, as well as multifocal c-KIT marking. Mutational study concluded a double mutation of KIT exon 9 and a mutation of PDGFRA exon 18. The patient was submitted to adjuvant treatment with imatinib mesylate 800 mg/day. Despite an extremely diverse presentation, omental EGISTs often remain clinically silent for a long time having enough space to grow before becoming symptomatic. These tumors have a consistent pattern of metastasis that typically spares lymph nodes unlike epithelial gut neoplasms. Surgery remains the preferred treatment for non-metastatic EGISTs of the greater omentum. It is possible that DOG-1 will supplant KIT as the leading marker in the future. The scarcity of knowledge on omental EGISTs implies a close monitoring of these patients to detect local relapse or distant metastasis.


Assuntos
Tumores do Estroma Gastrointestinal , Omento , Humanos , Feminino , Pessoa de Meia-Idade , Omento/cirurgia , Recidiva Local de Neoplasia/patologia , Mesilato de Imatinib/uso terapêutico , Mesentério/patologia , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/cirurgia
14.
Rozhl Chir ; 103(6): 224-227, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38991786

RESUMO

INTRODUCTION: Lymphangiomas belong to the group of benign vascular tumors that originate in the lymphatic tissue. Up to 90% of cases manifest in children before the second year of life. In adults, their presence is very rare. In most cases, they are located in the head, neck and axilla. Intra-abdominal lymphangiomas are very rare and represent less than 1% of all cases. CASE REPORT: The authors present the case of a 64-year-old female patient diagnosed with an intra-abdominal cystic lesion following a routine examination. A CT scan of the abdomen confirmed a cystic lesion located in the lesser omentum between the left lobe of the liver and the lesser curvature of the stomach. The patient was scheduled for laparoscopic exstirpation of the lesion. Histological examination confirmed the clinical diagnosis of cystic lymphangioma of the lesser omentum. CONCLUSION: The etiopathogenesis of lymphangiomas remains unclear. Despite the fact that they are benign tumors, lymphangiomas tend to have an infiltrative pattern of growth, invading surrounding structures. The majority of cases are asymptomatic and the diagnosis is incidental. The gold standard in treatment remains complete surgical extirpation with microscopically negative margins.


Assuntos
Linfangioma Cístico , Omento , Neoplasias Peritoneais , Humanos , Linfangioma Cístico/cirurgia , Linfangioma Cístico/patologia , Linfangioma Cístico/diagnóstico , Linfangioma Cístico/diagnóstico por imagem , Feminino , Omento/patologia , Omento/cirurgia , Pessoa de Meia-Idade , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/diagnóstico , Tomografia Computadorizada por Raios X
15.
Khirurgiia (Mosk) ; (8): 92-95, 2024.
Artigo em Russo | MEDLINE | ID: mdl-39140949

RESUMO

Internal hernias, in particular, hernia of the foramen of Winslow, are rare and occur in typical sites. Laparotomy is common in these cases while laparoscopic surgery is rarely used in such urgent cases. However, modern diagnosis and treatment including computed tomography and laparoscopy allowing minimally invasive interventions are not an exception for patients with hernia of the foramen of Winslow. This approach is effective for this problem and prevents adverse outcomes of disease.


Assuntos
Obstrução Intestinal , Laparoscopia , Tomografia Computadorizada por Raios X , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Obstrução Intestinal/diagnóstico , Laparoscopia/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Herniorrafia/métodos , Masculino , Doenças do Colo/cirurgia , Doenças do Colo/etiologia , Doenças do Colo/diagnóstico , Laparotomia/métodos , Hérnia Interna/complicações , Hérnia Interna/cirurgia , Hérnia Interna/diagnóstico , Hérnia Interna/etiologia , Feminino , Doença Aguda , Pessoa de Meia-Idade
16.
Cancer Invest ; 41(4): 330-344, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36227231

RESUMO

Ovarian cancer frequently metastasizes to the omentum, which is primarily comprised of adipocytes. Our previous study found that sucrose nonfermenting-related kinase (SNRK) expression is lower in advanced-stage compared with early-stage ovarian cancer tissue. In this study, SNRK knockdown was performed in ovarian cancer cell lines using lentiviral transduction and resulted in decreased cell proliferation, increased invasion, and a switch in metabolism to increased fatty acid oxidation (FAO). Our data suggest that SNRK works as a metabolic checkpoint that allows for oxidative phosphorylation and prevents FAO during a time of rapid tumor growth.


Assuntos
Neoplasias Ovarianas , Proteínas Serina-Treonina Quinases , Feminino , Humanos , Linhagem Celular , Ácidos Graxos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proteínas Serina-Treonina Quinases/genética
17.
Surg Endosc ; 37(9): 6704-6710, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37479840

RESUMO

BACKGROUND: Despite its extremely low incidence, intra-abdominal herniation through the lesser omentum is associated with a high mortality rate and must be recognized early and treated urgently. To overcome a lack of data on the management of this condition, we collected and reviewed all the reported cases of operated lesser omental hernia and presented the case of a patient treated by laparoscopy for an isolated lesser omental hernia. METHODS: According to PRISMA guidelines and using PubMed, Cochrane Library, and Web of Science, a systematic literature review of cases of lesser omental hernia treated by surgery was performed on February 12, 2023. RESULTS: Of 482 articles, 30 were included for analysis and only 9 articles presented an isolated hernia through the lesser omentum. Among these, 4 patients were female and the median age was 38. Upper abdominal pain and vomiting were reported in 7 out of 9 patients. The small bowel was responsible for 78% (7/9) of all lesser omental herniations. All of them were treated by laparotomy. In addition, we describe the case of a 65-year-old woman without prior surgical history who was treated by laparoscopy for a spontaneous closed loop hernia through the lesser omentum without any other associated hernias. CONCLUSION: Mostly associated with prior surgery or trauma, this type of herniation could sometimes occur spontaneously without any sign of peritonitis. Due to the high mortality rate, internal abdominal hernias should always be ruled out with a CT scan in front of patients presenting with persisting acute abdominal pain and no alternative diagnosis.


Assuntos
Laparoscopia , Omento , Humanos , Feminino , Adulto , Idoso , Masculino , Omento/cirurgia , Fígado , Dor Abdominal , Hérnia
18.
Int J Mol Sci ; 24(22)2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38003636

RESUMO

The omentum is the predominant site of ovarian cancer metastasis, but it is difficult to remove the omentum in its entirety. There is a critical need for effective approaches that minimize the risk of colonization of preserved omental tissues by occult cancer cells. Normal saline (0.9% sodium chloride) is commonly used to wash the peritoneal cavity during ovarian cancer surgery. The omentum has a prodigious ability to absorb fluid in the peritoneal cavity, but the impact of normal saline on the omentum is poorly understood. In this review article, we discuss why normal saline is not a biocompatible solution, drawing insights from clinical investigations of normal saline in fluid resuscitation and from the cytopathologic evaluation of peritoneal washings. We integrate these insights with the unique biology of the omentum and omental metastasis, highlighting the importance of considering the absorptive ability of the omentum when administering agents into the peritoneal cavity. Furthermore, we describe insights from preclinical studies regarding the mechanisms by which normal saline might render the omentum conducive for colonization by cancer cells. Importantly, we discuss the possibility that the risk of colonization of preserved omental tissues might be minimized by using balanced crystalloid solutions for peritoneal washing.


Assuntos
Neoplasias Ovarianas , Neoplasias Peritoneais , Humanos , Feminino , Solução Salina/uso terapêutico , Cavidade Peritoneal/patologia , Neoplasias Peritoneais/secundário , Lavagem Peritoneal , Neoplasias Ovarianas/patologia
19.
Int J Mol Sci ; 24(12)2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37372952

RESUMO

Ovarian cancer is the sixth leading cause of cancer-related death in women, and both occurrence and mortality are increased in women over the age of 60. There are documented age-related changes in the ovarian cancer microenvironment that have been shown to create a permissive metastatic niche, including the formation of advanced glycation end products, or AGEs, that form crosslinks between collagen molecules. Small molecules that disrupt AGEs, known as AGE breakers, have been examined in other diseases, but their efficacy in ovarian cancer has not been evaluated. The goal of this pilot study is to target age-related changes in the tumor microenvironment with the long-term aim of improving response to therapy in older patients. Here, we show that AGE breakers have the potential to change the omental collagen structure and modulate the peritoneal immune landscape, suggesting a potential use for AGE breakers in the treatment of ovarian cancer.


Assuntos
Produtos Finais de Glicação Avançada , Neoplasias Ovarianas , Humanos , Feminino , Idoso , Projetos Piloto , Colágeno , Neoplasias Ovarianas/tratamento farmacológico , Microambiente Tumoral
20.
Ceska Gynekol ; 88(6): 442-445, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38171917

RESUMO

This report concerns now 40-year-old healthy woman who was born alive and healthy from an ectopic pregnancy in the abdominal cavity, with placental localization on the omentum. This was a historical case report 40 years ago, as at that time doctors had little information about similar case in the world. Even today, in the era of modern medicine, we find only rare cases where a child developed outside the uterine cavity is born healthy and without developmental deformities. The mother subsequently had a normal intrauterine pregnancy 2 years later, ending with a caesarean section and the birth of a healthy boy.


Assuntos
Gravidez Abdominal , Adulto , Feminino , Humanos , Masculino , Gravidez , Cesárea , Placenta , Gravidez Abdominal/diagnóstico , Recém-Nascido
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