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1.
BMC Surg ; 22(1): 39, 2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35114982

RESUMO

BACKGROUND: Congenital abnormalities are not very common and are even rarer when two or more are combined. Congenital malformation of the superior mesenteric vein may not affect normal development, or it may lead to moderate or even severe symptoms. In combination with intestinal malrotation, however, it may lead to the need for surgical intervention in the early years of life. CASE PRESENTATION: We present the case of a 22-year-old patient who had been diagnosed with iron deficiency anaemia at the age of two months. As a result of the absence of the proximal section of the superior mesenteric vein, the patient has always needed iron supplements and an occasional erythrocyte transfusion. This has resulted from the formation of collaterals throughout the small bowel, causing chronic blood loss with its clinical manifestation. Although, there are some congenital abnormalities of the superior mesenteric vein, the absence of the superior mesenteric vein is rare, and in this case the clinical course was quite severe. Therefore, we planned bypass surgery for this patient to reduce the duodenal collaterals and resolve the persistent anaemia caused by chronic blood loss from the duodenum. We successfully performed the surgery consisting of the formation of anastomosis between the large collateral vein from the distal end of the superior mesenteric vein and the anterior inferior pancreaticoduodenal vein. CONCLUSION: The purpose of this case report is to describe the rare anatomical malformation of the superior mesenteric vein accompanied by intestinal malrotation, with its potential clinical implications regarding symptoms, clinical presentation, and the impact on potential surgery planning.


Assuntos
Anormalidades do Sistema Digestório , Volvo Intestinal , Adulto , Humanos , Lactente , Volvo Intestinal/diagnóstico por imagem , Volvo Intestinal/cirurgia , Intestino Delgado , Veias Mesentéricas/diagnóstico por imagem , Veias Mesentéricas/cirurgia , Veia Porta , Adulto Jovem
2.
Int J Mol Sci ; 23(4)2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35216235

RESUMO

Due to abundant stroma and extracellular matrix, accompanied by lack of vascularization, pancreatic ductal adenocarcinoma (PDAC) is characterized by severe hypoxia. Epigenetic regulation is likely one of the mechanisms driving hypoxia-induced epithelial-to-mesenchymal transition (EMT), responsible for PDAC aggressiveness and dismal prognosis. To verify the role of DNA methylation in this process, we assessed gene expression and DNA methylation changes in four PDAC cell lines. BxPC-3, MIA PaCa-2, PANC-1, and SU.86.86 cells were exposed to conditioned media containing cytokines and inflammatory molecules in normoxic and hypoxic (1% O2) conditions for 2 and 6 days. Cancer Inflammation and Immunity Crosstalk and Human Epithelial to Mesenchymal Transition RT² Profiler PCR Arrays were used to identify top deregulated inflammatory and EMT-related genes. Their mRNA expression and DNA methylation were quantified by qRT-PCR and pyrosequencing. BxPC-3 and SU.86.86 cell lines were the most sensitive to hypoxia and inflammation. Although the methylation of gene promoters correlated with gene expression negatively, it was not significantly influenced by experimental conditions. However, DNA methyltransferase inhibitor decitabine efficiently decreased DNA methylation up to 53% and reactivated all silenced genes. These results confirm the role of DNA methylation in EMT-related gene regulation and uncover possible new targets involved in PDAC progression.


Assuntos
Carcinoma Ductal Pancreático/genética , Metilação de DNA/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Expressão Gênica/genética , Neoplasias Pancreáticas/genética , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Epigênese Genética/genética , Humanos , Neoplasias Pancreáticas/patologia , Prognóstico , Neoplasias Pancreáticas
3.
Life (Basel) ; 14(9)2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39337958

RESUMO

To achieve an R0 resection margin in patients with locally advanced pancreatic ductal adenocarcinoma, high-volume pancreatic centers standardly incorporate portal vein or superior mesenteric vein resection. However, there is currently no consensus on the optimal reconstructive approach. Postoperative venous thrombosis or stenosis can significantly increase patient morbidity or mortality. The objective of this study was to report the long-term patency rate of portal/superior mesenteric vein reconstruction, as well as to identify potential predictors of postoperative venous thrombosis/stenosis. A single-center retrospective cohort analysis was conducted on patients undergoing pancreatic resection due to pancreatic tumor. The patency of the vascular reconstruction was assessed by routine surveillance using computed tomographic imaging at 3, 6, 9, and 12 months after surgery. A total of 297 pancreatic resections were performed with 53 patients undergoing concomitant venous resection. Among these, 26.4% (N = 14) had primary closure, 22.7% (N = 12) underwent an end-to-end anastomosis, and 50.9% (N = 27) received an interposition graft reconstruction. At the 1-year follow up, 90.2% (N = 37) of patients with venous reconstruction had a fully patent vein. The analysis did not reveal any statistically significant perioperative or postoperative factors associated with an increased risk of reconstruction thrombosis. While our study confirms a high long-term patency rate of 90.2% at 1 year, it underscores the necessity for a randomized controlled trial to determine the optimal method of venous reconstruction in pancreatic surgery.

4.
J Cardiothorac Surg ; 18(1): 164, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37118814

RESUMO

BACKGROUND: Pericardial effusions with its potential life threatening progression towards cardiac tamponade have to be often managed with surgical intervention. In our case study we describe a complication after a common surgical procedure which has only scarce literature mentions. CASE PRESENTATION: We present a case of a 22-year-old male patient who underwent subxiphoidal pericardial fenestration, due to symptomatic pericardial effusion with the Chamberlain procedure and biopsy of enlarged mediastinal lymph nodes. The histology report confirmed classical Hodgkin lymphoma and subsequently the patient underwent oncological treatment. Later on he was admitted to the hospital with dyspnoea and chest pain. The initial examinations stated a suspicion for intrathoracic tumour arising from the pericardium or liver. Further investigation revealed symptomatic intrathoracic liver herniation for which the patient underwent laparoscopic surgery with the mobilisation of liver and placement of a perforated Parietene™ composite mesh. CONCLUSION: The purpose of this case report is to describe a rare complication after pericardial fenestration with its potential clinical implications.


Assuntos
Tamponamento Cardíaco , Derrame Pericárdico , Masculino , Humanos , Adulto Jovem , Adulto , Pericárdio/patologia , Tamponamento Cardíaco/etiologia , Derrame Pericárdico/etiologia , Mediastino/patologia , Fígado/patologia
5.
Biomed Pharmacother ; 165: 115179, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37481927

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers worldwide, primarily due to its robust desmoplastic stroma and immunosuppressive tumor microenvironment (TME), which facilitate tumor progression and metastasis. In addition, fibrous tissue leads to sparse vasculature, high interstitial fluid pressure, and hypoxia, thereby hindering effective systemic drug delivery and immune cell infiltration. Thus, remodeling the TME to enhance tumor perfusion, increase drug retention, and reverse immunosuppression has become a key therapeutic strategy. In recent years, targeting epigenetic pathways has emerged as a promising approach to overcome tumor immunosuppression and cancer progression. Moreover, the progress in nanotechnology has provided new opportunities for enhancing the efficacy of conventional and epigenetic drugs. Nano-based drug delivery systems (NDDSs) offer several advantages, including improved drug pharmacokinetics, enhanced tumor penetration, and reduced systemic toxicity. Smart NDDSs enable precise targeting of stromal components and augment the effectiveness of immunotherapy through multiple drug delivery options. This review offers an overview of the latest nano-based approaches developed to achieve superior therapeutic efficacy and overcome drug resistance. We specifically focus on the TME and epigenetic-targeted therapies in the context of PDAC, discussing the advantages and limitations of current strategies while highlighting promising new developments. By emphasizing the immense potential of NDDSs in improving therapeutic outcomes in PDAC, our review paves the way for future research in this rapidly evolving field.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Nanomedicina , Sistemas de Liberação de Fármacos por Nanopartículas , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Microambiente Tumoral/genética , Neoplasias Pancreáticas
6.
J Vis Exp ; (195)2023 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-37306424

RESUMO

Tumor organoids are three-dimensional (3D) ex vivo tumor models that recapitulate the biological key features of the original primary tumor tissues. Patient-derived tumor organoids have been used in translational cancer research and can be applied to assess treatment sensitivity and resistance, cell-cell interactions, and tumor cell interactions with the tumor microenvironment. Tumor organoids are complex culture systems that require advanced cell culture techniques and culture media with specific growth factor cocktails and a biological basement membrane that mimics the extracellular environment. The ability to establish primary tumor cultures highly depends on the tissue of origin, the cellularity, and the clinical features of the tumor, such as the tumor grade. Furthermore, tissue sample collection, material quality and quantity, as well as correct biobanking and storage are crucial elements of this procedure. The technical capabilities of the laboratory are also crucial factors to consider. Here, we report a validated SOP/protocol that is technically and economically feasible for the culture of ex vivo tumor organoids from fresh tissue samples of pancreatic adenocarcinoma origin, either from fresh primary resected patient donor tissue or patient-derived xenografts (PDX). The technique described herein can be performed in laboratories with basic tissue culture and mouse facilities and is tailored for wide application in the translational oncology field.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Animais , Camundongos , Bancos de Espécimes Biológicos , Fibroblastos , Organoides , Microambiente Tumoral , Neoplasias Pancreáticas
7.
Cancers (Basel) ; 13(18)2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34572959

RESUMO

Cell senescence constitutes a physiological process that serves as protection from malignant transformation of cells. However, recent scientific discoveries also identify cell senescence as pivotal in hepatocellular cancer (HCC) biology. The review herein aimed to accumulate evidence on senescence as a mediator of HCC occurrence in hepatitis B (HBV), C (HCV) virus infections, and non-alcoholic fatty liver disease (NAFLD). In HBV infection, the carcinogenic HBV X protein frequently mutates during chronic infection, and subsequently exhibits different effects on senescence. In HCV infection, senescent non-functional T-cells do not effectively clear pre-malignant hepatocytes. Furthermore, the HCV Core protein inhibits the occurrence of normal stress-induced hepatocyte senescence, allowing damaged cells to maintain their proliferative potential. In NAFLD-mediated HCC, current data point towards the gut microbiome and hepatic stellate cell senescence. Additionally, senescence contributes in the development of resistance in targeted therapies, such as sorafenib. Finally, the promising role of senotherapeutics in HCC was also explored. Overall, although we may still be at a primitive stage in fully unraveling the role of senescence in cancer, it seems that understanding and harnessing senescence may have the potential to revolutionize the way we treat hepatocellular cancer.

8.
J Neuroimmunol ; 330: 123-129, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30875612

RESUMO

In this study, we analysed the association of rs703842 in CYP27B1 gene with multiple sclerosis (MS) risk and disability progression in a group of 496 MS patients and 521 controls. For the first time in Central European Slovak population, we found the rs703842 allele C to be protective factor against MS development (p = 1.09 × 10-5). Moreover, the risky genotypes TT and TC were showed to be associated with an increased MS risk, and this was aggravated by the homozygous carriage of the HLA-DRB1*15:01 allele (OR = 2.82 vs. 4.86, p < .0001). No association of rs703842 with MS disability progression or calcidiol serum level was found.


Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Alelos , Predisposição Genética para Doença/genética , Variação Genética/genética , Cadeias HLA-DRB1/genética , Esclerose Múltipla/genética , Adulto , Feminino , Estudos de Associação Genética/métodos , Predisposição Genética para Doença/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/epidemiologia , Eslováquia/epidemiologia
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