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Aldehyde dehydrogenase (ALDH) enzymatic activity is a marker of cancer-initiating cells (CIC) in many tumor types. Our group and others have found that ALDH1A family inhibitors (ALDHi) can preferentially induce death of ovarian CIC in established ovarian cancer. We sought to determine if ALDHi, by targeting CIC at the time of tumor initiation, could function as a chemopreventive for ovarian cancer. As BRCA1/2 mutation carriers represent a population who could benefit from an ovarian cancer chemopreventive, we focused on BRCA mutation-associated tumor cell lines and murine tumor models. We found that, compared to BRCA wild-type cells, BRCA mutant ovarian cancer cells are more sensitive to the ALDHi673A. Similarly, while 673A treatment of wild-type fallopian tube epithelial (FTE) cells is non-toxic, 673A induces death in FTE cells with BRCA1 knockdown. Using a murine fallopian tube organoid model of ovarian carcinogenesis, we show that 673A reduced organoid complexity and significantly reduce colony formation of BRCA-mutant cells. Organoids that persisted after 673A treatment were predominantly BRCA1wt, but NF1 mutant, suggesting a resistance mechanism. Finally, using the BPRN (Brca1, Trp53, Rb1, Nf1 inactivated) mouse model of tubo-ovarian cancer, we evaluated the impact of intermittent 673A therapy on carcinogenesis. 673A treatment resulted in a significant reduction in serous tubal intraepithelial carcinoma (STIC) lesions and carcinomas. Collectively, the findings suggest that ALDHi, such as 673A, could serve as chemopreventive agents for BRCA1/2 mutation carriers.
Assuntos
Cistadenocarcinoma Seroso , Neoplasias das Tubas Uterinas , Neoplasias Ovarianas , Feminino , Humanos , Camundongos , Animais , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Proteína BRCA2/genética , Mutação , Neoplasias das Tubas Uterinas/patologia , Tubas Uterinas/patologia , Cistadenocarcinoma Seroso/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/metabolismo , Inibidores Enzimáticos , Quimioprevenção , CarcinogêneseRESUMO
Background: A specific cause of superior vena cava (SVC) syndrome, SVC thrombosis, is a rare but known complication in cancer patients. Early identification and management of SVC thrombosis in lung cancer patients may lead to improved patient outcomes and a reduction in healthcare costs. Methods: We studied the racial and socioeconomic differences, length of stay, total hospital charges, and all-cause mortality outcomes in patients with lung cancer with and without SVC thrombosis using data from the National Inpatient Sample. Statistical analysis was performed on STATA. Results: A total of 480,750 patients were hospitalized for lung cancer; 720 (0.15%) of these patients had SVC thrombosis. The lung cancer with SVC thrombosis cohort had a statistically higher proportion of Black patients. Patients with lung cancer presenting with SVC thrombosis had an increased hospital length of stay (10 vs 6 days, P < 0.001) and cost ($117,320 vs $80,806, P < 0.005) compared to those without SVC thrombosis. All-cause mortality in patients with lung cancer was 7.7% and the presence of SVC thrombosis significantly increased the odds of inpatient mortality (18.0%). Nonwhite races were associated with higher odds of mortality in lung cancer admissions. Conclusion: Race, insurance type, and comorbidities impacted the likelihood of developing SVC thrombosis in patients with lung cancer. SVC thrombosis is a poor prognostic factor for patients with lung cancer. Further studies to evaluate these disparities are warranted.
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Introduction Diffuse large B-cell lymphoma (DLBCL) may be complicated by hypercalcemia at various stages of treatment. The impact of hypercalcemia on chemotherapy admission outcomes in DLBCL is not well described. Methods In a retrospective analysis, using the National Inpatient Sample database (2018 - 2020), patients with DLBCL admitted for chemotherapy were dichotomized based on the presence of hypercalcemia. Our primary outcome was all-cause mortality. Secondary outcomes included length of stay (LOS), total charge, rate of acute kidney injury (AKI), tumor lysis syndrome (TLS), hyperkalemia, metabolic acidosis, acute encephalopathy, septic shock, Clostridiodes difficile infection, acute respiratory failure, and venous thromboembolic events (VTE). Results We identified 78,955 patients, among whom 1,375 (1.74%) had hypercalcemia. Hypercalcemia was associated with higher odds of all-cause mortality (aOR:3.05, p-value:0.020), TLS (aOR:8.81, p-value<0.001), acute metabolic encephalopathy (aOR:4.89, p-value<0.001), AKI (aOR:5.29, p-value<0.001), hyperkalemia (aOR:2.84, p-value:0.002), metabolic acidosis (aOR:3.94, p-value<0.001) and respiratory failure (aOR:2.29, p-value:0.007) and increased LOS by 1 day and total charge by 12, 501 USD. Conclusions In patients with DLBCL admitted for inpatient chemotherapy, those with hypercalcemia compared to a cohort without had higher odds of; all-cause mortality, TLS, AKI, acute encephalopathy, acute metabolic acidosis, hyperkalemia, and acute respiratory failure as well as higher LOS and total charge.
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Background: Colorectal cancer (CRC) poses a significant burden on healthcare systems globally. Sociodemographic factors intricately influence CRC epidemiology, yet their impact on inpatient care remains underexplored. This study aimed to assess trends in CRC hospitalization and the effect of sociodemographic factors on outcomes of CRC patients. Methods: A retrospective longitudinal analysis was conducted using data from the Healthcare Cost and Utilization Project National Inpatient Sample. Trends in CRC admissions were assessed, stratified by sociodemographic variables. Disparities in hospital-associated outcomes were examined. Statistical methods included multivariable regression and joinpoint regression analysis. Results: The prevalence of CRC hospitalizations uptrended from 760 per 100,000 hospitalizations in 2010 to 841 per 100,000 hospitalizations in 2019 (P trend < 0.001). The mean age decreased from 67 to 66 years (P < 0.001). Male gender and White race were predominant across the study period. Inpatient mortality decreased from 4.5% in 2010 to 4.16% in 2019 (P trend = 0.033). On sex subgroup analysis, men had a significantly higher mortality rate (P = 0.034). Racially, Blacks had the highest mortality rate (P = 0.550) and only Whites showed a significant decline in mortality over the study period (P = 0.003). Hospitalization length decreased while total hospital charges increased. Conclusion: Our study highlights sociodemographic disparities in CRC outcomes, emphasizing the need for targeted interventions to address inequity in screening, diagnosis, and treatment. Continued research is needed to inform effective healthcare practices in mitigating these disparities and improving survival outcomes.
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Angiosarcomas are a rare subtype of sarcomas originating from vascular endothelial cells. Though frequently found in the head and neck area, there are minimal reports of radiation-induced angiosarcomas in this area. They have a poor prognosis due to a high rate of lymph node metastasis and, hence, require to be addressed promptly in order to improve survival. We present a rare case of radiation-induced angiosarcoma in a patient previously irradiated for squamous cell carcinoma of the neck. Due to variable and complex patient presentations of the disease, this case will help raise awareness of an uncommon complication of a common treatment offered to patients.
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Background Thoracic irradiation is a widely used therapeutic and palliative treatment option for thoracic neoplasms. However, short- and long-term cardiovascular adverse effects of radiation exposure remain a major concern. The short-term adverse effects are observed within months of exposure such as pericardial diseases; meanwhile, the long-term complications are usually insidious and manifest over decades, such as congestive heart failure, coronary artery disease, cardiomyopathy, conduction disorders, constrictive pericarditis, and valvular heart disease. Hence, long-term cardiovascular adverse effects are challenging to predict, and the association with radiation exposure remains difficult to establish. Methodology This retrospective, observational study was conducted using data from the National Inpatient Sample (NIS) database from 2016 to 2019. Adult patients with primary thoracic malignancies who underwent radiation therapy (RT) were defined using principal and secondary International Classification of Diseases, Tenth Revision codes. Other malignancies that can be treated with RT and all secondary malignancies were excluded from the primary comparison group. Cardiac outcomes were defined as the prevalence of congestive heart failure, coronary artery disease, cardiomyopathy, conduction disorders, pericardial diseases, and valvular heart diseases in the primary group. The multivariate logistic and the linear regression analyses were used to adjust for confounders. Results When compared to the general population, adults with thoracic malignancies exposed to RT had higher odds of developing chronic pericarditis (adjusted odds ratio (aOR) = 2, 95% confidence interval (CI) = 1.9-2.2, p < 0.001), acute pericarditis (aOR = 2.3, 95% CI = 1.9-2.9, p < 0.001), constrictive pericarditis (aOR = 2.8, 95% CI = 2.1-3.7, p < 0.001), conduction disorders (aOR = 1.3, 95% CI = 1.2-1.35, p < 0.001), coronary artery disease (aOR = 1.24, 95% CI = 1.2-1.27, p < 0.001), heart failure (aOR = 1.44, 95% CI = 1.4-1.5, p < 0.001), and valvular heart disease (aOR = 1.37, 95% CI = 1.3-1.4, p < 0.001). There was no difference in the odds of developing cardiac arrest (aOR = 1, 95% CI = 0.9-1.10, p = 0.6) or acute myocardial infarction (aOR = 1.1, 95% CI = 1-1.15, p < 0.001). When compared to adults with thoracic malignancies not exposed to RT, adults with thoracic malignancies who were exposed to RT had higher odds of developing acute myocardial infarction (aOR = 1.14, 95% CI = 1.1-1.18, p < 0.001), chronic pericarditis (aOR = 1.3, 95% CI = 1.2-1.3, p < 0.001), acute pericarditis (aOR = 1.6, 95% CI = 1.2-2.1, p < 0.001), constrictive pericarditis (aOR = 2.2, 95% CI = 1.5-3.2, p < 0.001), conduction disorders (aOR = 1.1, 95% CI = 1.08-1.13, p < 0.001), coronary artery disease (aOR = 1.14, 95% CI = 1.12-1.16, p < 0.001), heart failure (aOR = 1.2, 95% CI = 1.17-1.23, p < 0.001), and valvular heart disease (aOR = 1.3, 95% CI = 1.2-1.35, p < 0.001). The odds were similar between the two groups for developing cardiac arrest (aOR = 0.86, 95% CI = 0.8-0.98, p = 0.05). Conclusions Adults with thoracic malignancies who were treated with RT have higher odds of developing chronic pericarditis, acute pericarditis, constrictive pericarditis, conduction disorders, coronary artery disease, heart failure, and valvular heart disease while similar odds of developing cardiac arrest or acute myocardial infarction compared to the general adult population.
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Prostate cancer is the third most diagnosed cancer in men around the world, and it typically metastasizes to bone, lung, and liver. Gastrointestinal (GI) involvement by prostate cancer is rare, as patients tend to present with upper and lower GI bleed among other symptoms not related to prostate cancer, which commonly include lower urinary tract symptoms such as urinary frequency, dribbling of urine, or urinary retention. In cases of patients with prostate cancer and symptoms from the GI system, colonoscopy and biopsy of lesions should be performed to allow physicians to make an accurate and prompt diagnosis in patients with metastatic prostate cancer with rectal involvement. We present a case of a patient who initially complained of melena and was found to have a rectal nodule with biopsy-proven metastatic prostate cancer.