RESUMO
RATIONALE AND OBJECTIVES: To identify if body composition, assessed with preoperative CT-based visceral fat ratio quantification as well as tumor metabolic gene expression, predicts sex-dependent overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: This was a retrospective analysis of preoperative CT in 98 male and 107 female patients with PDAC. Relative visceral fat (rVFA; visceral fat normalized to total fat) was measured automatically using software and corrected manually. Median and optimized rVFA thresholds were determined according to published methods. Kaplan Meier and log-rank tests were used to estimate OS. Multivariate models were developed to identify interactions between sex, rVFA, and OS. Unsupervised gene expression analysis of PDAC tumors from The Cancer Genome Atlas (TCGA) was performed to identify metabolic pathways with similar survival patterns to rVFA. RESULTS: Optimized preoperative rVFA threshold of 38.9% predicted significantly different OS in females with a median OS of 15 months (above threshold) vs 24 months (below threshold; p = 0.004). No significant threshold was identified in males. This female-specific significance was independent of age, stage, and presence of chronic pancreatitis (p = 0.02). Tumor gene expression analysis identified female-specific stratification from a five-gene signature of glutathione S-transferases. This was observed for PDAC as well as clear cell renal carcinoma and glioblastoma. CONCLUSION: CT-based assessments of visceral fat can predict pancreatic cancer OS in females. Glutathione S-transferase expression in tumors predicts female-specific OS in a similar fashion.
Assuntos
Gordura Intra-Abdominal , Neoplasias Pancreáticas , Tomografia Computadorizada por Raios X , Humanos , Feminino , Masculino , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/metabolismo , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Idoso , Glutationa/metabolismo , Fatores Sexuais , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/genética , Adulto , Idoso de 80 Anos ou mais , Taxa de SobrevidaRESUMO
A 61-year-old HIV+ male presented to an infectious disease clinic with a complaint of sore throat. A painless ulcerated mass was discovered on the right tonsil resulting in further evaluation with a CT scan of the neck. Imaging confirmed the presence of a mass centered on the palatine tonsil and associated lymphadenopathy. A presumptive diagnosis of HPV-related squamous cell carcinoma was made due to patient risk factors. However, multiple biopsies found no evidence of carcinoma, but instead revealed the presence of spirochetes that stained positive for T Pallidum. Soon after, the patient developed the characteristic copper-red maculopapular rash of secondary syphilis, indicating that the tonsillar mass was, in fact, a primary chancre. Since such chancres are most often found externally in the genital or anal region, they are seldom radiographically characterized, placing them low on the differential diagnosis for most radiologists. A high index of suspicion could aid future radiologists in placing primary syphilis higher on the differential diagnosis in similar cases in which the patient has appropriate risk factors, such as a known history of genital-oral sexually transmitted infections or an immunocompromised state. Prompt recognition of the nature of a primary syphilitic lesion can lead to rapid resolution of symptoms following treatment with intramuscular benzathine penicillin G, as eventually occurred in this case.
RESUMO
Accurate and sensitive point-of-care diagnostic tools are critical for schistosomiasis control and elimination. The existing ultrasensitive lateral flow assay for the detection of Schistosoma circulating anodic antigen (CAA) has demonstrated excellent sensitivity but is time-consuming and requires significant laboratory infrastructure that limits its applicability at the point of care. To address this challenge, we sought to develop an alternative sample preparation method to concentrate CAA from large-volume urine samples requiring little-to-no laboratory equipment. The developed method relies on electrostatic interactions between the negatively-charged CAA biomarker and positively-charged poly(amidoamine) (PAMAM) dendrimers functionalized to the surface of magnetic particles. After CAA capture on the surface of the PAMAM-functionalized magnetic beads, the supernatant was removed, and CAA was eluted into a small-volume, high-salt elution buffer. This concentrated eluate was subsequently applied to the existing lateral flow assay. The PAMAM-functionalized magnetic bead-based CAA concentration method was extensively characterized for its robustness, evaluated on a set of endemic urine samples, and compared to spin filter-based concentration methods. The novel bead-based sample preparation method used only disposable laboratory materials, resulted in a 200-fold improvement in CAA limits of detection, and performed just as well as infrastructure-intensive and high-cost spin filter methods. Additionally, the functionalized beads were robust to variations in sample pH and storage conditions. The PAMAM-functionalized magnetic bead-based CAA concentration method represents a promising step toward ultrasensitive schistosomiasis diagnosis at the point of care.