RESUMO
Optimal clinical outcomes in cancer treatments could be achieved through the development of reliable, precise ex vivo tumor models that function as drug screening platforms for patient-targeted therapies. Microfluidic tumor-on-chip technology is emerging as a preferred tool since it enables the complex set-ups and recapitulation of the physiologically relevant physical microenvironment of tumors. In order to overcome the common hindrances encountered while using this technology, a fully 3D-printed device was developed that sustains patient-derived multicellular spheroids long enough to conduct multiple drug screening tests. This tool is both cost effective and possesses four necessary characteristics of effective microfluidic devices: transparency, biocompatibility, versatility, and sample accessibility. Compelling correlations which demonstrate a clinical proof of concept were found after testing and comparing different chemotherapies on tumor spheroids, derived from ten patients, to their clinical outcomes. This platform offers a potential solution for personalized medicine by functioning as a predictive drug-performance tool.
Assuntos
Neoplasias , Medicina de Precisão , Humanos , Avaliação Pré-Clínica de Medicamentos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Impressão Tridimensional , Dispositivos Lab-On-A-Chip , Microambiente TumoralRESUMO
Sarcoma classification is challenging and can lead to treatment delays. Previous studies used DNA aberrations and machine-learning classifiers based on methylation profiles for diagnosis. We aimed to classify sarcomas by analyzing methylation signatures obtained from low-coverage whole-genome sequencing, which also identifies copy-number alterations. DNA was extracted from 23 suspected sarcoma samples and sequenced on an Oxford Nanopore sequencer. The methylation-based classifier, applied in the nanoDx pipeline, was customized using a reference set based on processed Illumina-based methylation data. Classification analysis utilized the Random Forest algorithm and t-distributed stochastic neighbor embedding, while copy-number alterations were detected using a designated R package. Out of the 23 samples encompassing a restricted range of sarcoma types, 20 were successfully sequenced, but two did not contain tumor tissue, according to the pathologist. Among the 18 tumor samples, 14 were classified as reported in the pathology results. Four classifications were discordant with the pathological report, with one compatible and three showing discrepancies. Improving tissue handling, DNA extraction methods, and detecting point mutations and translocations could enhance accuracy. We envision that rapid, accurate, point-of-care sarcoma classification using nanopore sequencing could be achieved through additional validation in a diverse tumor cohort and the integration of methylation-based classification and other DNA aberrations.
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BACKGROUND: Giant inguinal hernia (GIH) is a rare condition in the developed world, and the literature is scarce. Case reports describe different techniques in an attempt to prevent abdominal compartment syndrome (ACS). We aimed to review our experience with GIH repair. METHOD: A retrospective review of the medical records of all consecutive patients who underwent a tension-free mesh GIH repair using a transverse inguinal incision between 2014 and 2021 at a tertiary university referral center. In brief, the technique included head-down positioning, maximal pre-incision reduction of hernia contents, and repair with mesh. Follow-up was conducted in outpatient clinic. We compared the results to a time-based open standard inguinal hernia repair group (control group). RESULTS: During the study period, 58 patients underwent an open GIH repair with mesh without abdominal preparation. 232 patients were included in the control group. The mean surgery duration was 125.5 min in the GIH group and 84 min in the control group (p < 0.001). Bowel resection was not necessary in any case. In-hospital complication rates were 13.8% vs. 5.6% in the GIH and control groups, respectively (p = 0.045). Early complication rates (up to 30 days post-operatively) were 62.1% vs. 14.7% in the GIH and control groups, respectively (p < 0.001). Late complications rate was similar (p = 0.476). ACS and mortality were not reported. No recurrence event was reported in the GIH group. CONCLUSION: Tension-free mesh repair for GIH using a standard transverse inguinal incision is feasible and safe and there is no need for abdominal cavity preparation. Early complications are more common than in the control group, but there were no higher rate of late or severe complications and no recurrence event.
Assuntos
Hérnia Inguinal , Humanos , Hérnia Inguinal/cirurgia , Estudos Retrospectivos , Estudos de Casos e Controles , Telas Cirúrgicas , Virilha/cirurgia , Herniorrafia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND Behcet's disease (BD) is defined as vasculitis involving arteries and veins of any size and affecting almost any organ system. Abdominal manifestations of BD are diverse and nonspecific. Mucosal ulcerations can be seen in the gastrointestinal tract. Extensive ulcerations, especially ileocecal lesions, can lead to perforation, strictures, fistulas, and abscesses. Pneumatosis cystoides intestinale is a rare benign condition characterized by multiple submucosal or subserosal, gas-filled cysts in the gastrointestinal tract wall. Pneumatosis cystoides coli (PCC) affects the colon, can present with a wide range of manifestations, and can mimic many different systemic diseases. We describe a case of PCC in a patient with Behcet's disease who presented to the Emergency Department with a clinical suspicion of acute abdomen. CASE REPORT A 40-year-old man with complicated Behcet's disease, treated with high-dose steroids, presented with acute abdomen and CT scan findings highly suggestive of intestinal obstruction due to ileocolic intussusception. He underwent laparoscopic right hemicolectomy. Pathology demonstrated PCC disease. CONCLUSIONS Pneumatosis cystoides coli can present with a broad range of symptoms and can be secondary to many systemic and autoimmune diseases. With radiological evidence and a high level of suspicion, unnecessary surgery can be prevented.
Assuntos
Abdome Agudo , Síndrome de Behçet , Pneumatose Cistoide Intestinal , Masculino , Humanos , Adulto , Abdome Agudo/etiologia , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Pneumatose Cistoide Intestinal/complicações , Pneumatose Cistoide Intestinal/diagnóstico , Colo , RadiografiaRESUMO
OBJECTIVE: Cellular senescence limits tumourigenesis by blocking the proliferation of premalignant cells. Additionally, however, senescent cells can exert paracrine effects influencing tumour growth. Senescent cells are present in premalignant pancreatic intraepithelial neoplasia (PanIN) lesions, yet their effects on the disease are poorly characterised. It is currently unknown whether senolytic drugs, aimed at eliminating senescent cells from lesions, could be beneficial in blocking tumour development. DESIGN: To uncover the functions of senescent cells and their potential contribution to early pancreatic tumourigenesis, we isolated and characterised senescent cells from PanINs formed in a Kras-driven mouse model, and tested the consequences of their targeted elimination through senolytic treatment. RESULTS: We found that senescent PanIN cells exert a tumour-promoting effect through expression of a proinflammatory signature that includes high Cox2 levels. Senolytic treatment with the Bcl2-family inhibitor ABT-737 eliminated Cox2-expressing senescent cells, and an intermittent short-duration treatment course dramatically reduced PanIN development and progression to pancreatic ductal adenocarcinoma. CONCLUSIONS: These findings reveal that senescent PanIN cells support tumour growth and progression, and provide a first indication that elimination of senescent cells may be effective as preventive therapy for the progression of precancerous lesions.