Description of Solvent-Extractable Chemicals in Thermal Receipts and Toxicological Assessment of Bisphenol S and Diphenyl Sulfone.

Research on thermal receipts has previously focused on the toxic effects of dermal exposure from the most publicized developers (e.g., bisphenol A (BPA) and bisphenol S (BPS)), while no studies have reported on the other solvent-extractable compounds therein. Diphenyl sulfone (DPS) is a sensitizer added to thermal receipts, but little is known about DPS concentrations in receipts or potential toxicity. Here, we quantified BPA, BPS, and DPS concentrations and tentatively identified the solvent-extractable compounds of thermal receipts collected from three South Dakota (USA) cities during 2016-2017. An immortalized chicken hepatic cell line, cultured as 3D spheroids, was used to screen effects of DPS, BPS, and 17ß estradiol (E2; 0.1-1000 µM) on cell viability and gene expression changes. These chemicals elicited limited cytotoxicity with LC50 values ranging from 113 to 143 µM, and induced dysregulation in genes associated with lipid and bile acid homeostasis. Taken together, this study generated novel information on solvent-extractable chemicals from thermal receipts and toxicity data for DPS.

Potentio-tunable FET sensor having a redox-polarizable single electrode for the implementation of a wearable, continuous multi-analyte monitoring device.

The emerging field of wearable devices for monitoring bioanalytes calls for the miniaturization of biochemical sensors. The only commercially available electrochemical wearable monitoring medical devices for bioanalytes are the amperometric continuous glucose monitoring (CGM) systems. The use of such amperometric methods to monitor glucose levels requires a relatively large electrode surface area for sufficient redox species collection, allowing accurate measurements to be made. Consequently, miniaturization of such sensors bearing large electrodes is challenging. Furthermore, it is difficult to introduce and deploy more than one electrode-based sensor per device, thereby limiting the number of analytes that can be monitored in parallel. To address these limitations, we have employed a non-referenced, single polarizable electrode coupled to a fin-shaped field-effect transistor (Fin-FET). We have discovered that by passivating the FET area by a relatively thick oxide and/or polytetrafluoroethylene (PTFE) polymer, leaving only the polarizable working electrode (WE) exposed, we can monitor redox analytes at the micromolar to millimolar concentration range. We attribute this effect to the WE polarization by the solution redox species. We have exploited the superior sensitivity of the adjacent silicon-based Fin-FET to detect changes in sensor electrode potentials induced by the redox species. Furthermore, we demonstrated the correlation between a specific analyte and the biasing WE potential on the accumulation/depletion of the coupled Fin-FET channel as manifested by the transistor source-drain current. Moreover, we utilized the analyte-electrode potential interaction, which is analyte-specific, to tune the specificity of the sensor towards an analyte of choice. In addition, we demonstrated the use of a single-electrode potentiometric sweep to assist in identifying the accumulation/depletion as a result of analyte-WE state. Collectively, the tiny potentio-tunable electrochemical sensor (PTEchem sensor) area is ~50 × 50 µm, and dedicated wireless transducer facilitates the use of this sensor for wearable continuous, multi-metabolite monitoring.

A Novel Background Modeling Algorithm for Hyperspectral Ground-Based Surveillance and Through-Foliage Detection.

Foliage penetration is an unsolved important part of border surveillance of remote areas between regular border crossing points. Detecting penetrating objects (e.g., persons and cars) through dense foliage in various climate conditions using visual sensors is prone to high fault rates. Through-foliage scenarios contain an unprecedented amount of occlusion-in fact, they often contain fragmented occlusion (for example, looking through the branches of a tree). Current state-of-the-art detectors based on deep learning perform inadequately under moderate-to-heavy fragmented occlusion. The FOLDOUT project builds a system that combines various sensors and technologies to tackle this problem. Consequently, a hyperspectral sensor was investigated due to its extended spectral bandwidth, beyond the range of typical RGB sensors, where vegetation exhibits pronounced reflectance. Due to the poor performance of deep learning approaches in through-foliage scenarios, a novel background modeling-based detection approach was developed, dedicated to the characteristics of the hyperspectral sensor, namely strong correlations between adjacent spectral bands and high redundancy. The algorithm is based on local dimensional reduction, where the principal subspace of each pixel is maintained and adapted individually over time. The successful application of the proposed algorithm is demonstrated in a through-foliage scenario comprised of heavy fragmented occlusion and a highly dynamical background, where state-of-the-art deep learning detectors perform poorly.

Contemporary prostate cancer treatment choices in multidisciplinary clinics referenced to national trends.

BACKGROUND: The purpose of this study was to assess treatment choices among men with prostate cancer who presented at The University of Texas MD Anderson Cancer Center multidisciplinary (MultiD) clinic compared with nationwide trends. METHODS: In total, 4451 men with prostate cancer who presented at the MultiD clinic from 2004 to 2016 were analyzed. To assess nationwide trends, the authors analyzed 392,710 men with prostate cancer who were diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was treatment choice as a function of pretreatment demographics. RESULTS: Univariate analyses revealed similar treatment trends in the MultiD and SEER cohorts. The use of procedural forms of definitive therapy decreased with age, including brachytherapy and prostatectomy (all P < .05). Later year of diagnosis/clinic visit was associated with decreased use of definitive treatments, whereas higher risk grouping was associated with increased use (all P < .001). Patients with low-risk disease treated at the MultiD clinic were more likely to receive nondefinitive therapy than patients in SEER, whereas the opposite trend was observed for patients with high-risk disease, with a substantial portion of high-risk patients in SEER not receiving definitive therapy. In the MultiD clinic, African American men with intermediate-risk and high-risk disease were more likely to receive definitive therapy than white men, but for SEER the opposite was true. CONCLUSIONS: Presentation at a MultiD clinic facilitates the appropriate disposition of patients with low-risk disease to nondefinitive strategies of patients with high-risk disease to definitive treatment, and it may obviate the influence of race.

Patterns of Care and Comparison of Outcomes Between Primary Anal Squamous Cell Carcinoma and Anal Adenocarcinoma.

BACKGROUND: The management of adenocarcinoma of the anus can be challenging because there are few data on outcomes and trends in its treatment to date. OBJECTIVE: This study aimed to compare and analyze the patterns of care and survival outcomes of patients with anal squamous cell carcinoma and anal adenocarcinoma. DESIGN: This was a retrospective study. SETTING: This study was performed by utilizing the National Cancer Database. PATIENTS: We selected a total of 19,539 patients between 2004 and 2014 with stage II to III squamous cell carcinoma or adenocarcinoma of the anus. INTERVENTION: The treatment groups analyzed were surgery alone, neoadjuvant chemoradiation followed by surgery, surgery followed by adjuvant chemoradiation, or definitive chemoradiation. MAIN OUTCOME MEASURES: Patient- and clinical-related factors were compared between the 2 groups. Kaplan-Meier and Cox proportional hazards regression models were used to assess overall survival. RESULTS: Of the patients studied, 18,346 (93.9%) had primary squamous cell carcinoma and 1193 (6.1%) had primary adenocarcinoma of the anus. The 5-year overall survival for stage II squamous cell carcinoma was 69.2%, and, for stage II adenocarcinoma, 5-year overall survival was 54.2% (p < 0.001). The 5-year overall survival for stage III squamous cell carcinoma was 55.2%, and, for stage III adenocarcinoma, 5-year overall survival was 32.9% (p < 0.001). On multivariable Cox regression, treatment with chemoradiation alone (HR, 0.67; p = 0.008) was associated with improved survival in squamous cell carcinoma. For the adenocarcinoma group, stage III disease (HR, 2.26; p < 0.001) and high tumor grade (HR, 1.59; p < 0.011) had a negative impact on survival, but there were no differences in survival based on the type of treatment received. LIMITATIONS: The National Cancer Database does not include information on specific chemotherapeutic or immunotherapy agents given to patients, nor does it provide the exact cause of death. CONCLUSIONS: Anal adenocarcinoma in comparison to anal squamous cell carcinoma had a lower 5-year overall survival stage for stage. Anal adenocarcinoma appears to be treated similarly to the rectal cancer paradigm, with frequent use of neoadjuvant chemoradiation. See Video Abstract at http://links.lww.com/DCR/B50. PATRONES DE EL CUIDADO Y COMPARACIÓN DE RESULTADOS ENTRE EL CARCINOMA DE CÉLULAS ESCAMOSAS ANAL PRIMARIO Y EL ADENOCARCINOMA ANAL: El tratamiento del adenocarcinoma del ano puede ser un desafío ya que hasta la fecha, hay pocos datos sobre los resultados y las tendencias en su tratamiento.Comparar y analizar los patrones de el cuidado y resultados de supervivencia de pacientes con carcinoma anal de células escamosas y adenocarcinoma anal.Este fue un estudio retrospectivo.Este estudio se realizó utilizando la Base de Datos Nacional de Cancer (National Cancer Database, NCB).Seleccionamos un total de 19,539 pacientes entre el 2004-2014 con carcinoma de células escamosas en estadio II-III o adenocarcinoma del ano.Los grupos de tratamiento analizados fueron solo cirugía, quimiorradiación neoadyuvante seguida por cirugía, cirugía seguida por quimiorradiación adyuvante o quimiorradiación definitiva.Se compararon los factores clínicos y de pacientes entre los dos grupos. Se utilizaron modelos de regresión de riesgos proporcionales de Kaplan-Meier y Cox para evaluar la supervivencia general.18,346 (93.9%) tenían carcinoma primario de células escamosas y 1,193 (6.1%) tenían adenocarcinoma primario del ano. La supervivencia global a 5 años para el carcinoma de células escamosas en estadio II fue del 69.2% y para el adenocarcinoma en estadio II fue del 54.2% (p < 0.001). La supervivencia global a cinco años para el carcinoma de células escamosas en estadio III fue del 55.2% y para el adenocarcinoma en estadio III fue del 32.9% (p < 0.001). En la regresión de Cox multivariable, el tratamiento con quimiorradiación sola (proporción de riesgo 0.67, p = 0.008) se asoció con una mejor supervivencia en el carcinoma de células escamosas. Para el grupo de adenocarcinoma, la enfermedad en estadio III (proporción de riesgo 2.26, p < 0.001) y el alto grado tumoral (proporción de riesgo 1.59, p < 0.011) tuvieron un impacto negativo en la supervivencia, pero no hubo diferencias en la supervivencia según el tipo de tratamiento recibido.La Base de Datos Nacional de Cancer no incluye información sobre agentes quimioterapéuticos o de inmunoterapia específicos que se administran a los pacientes, ni proporciona la causa exacta de la muerte.El adenocarcinoma anal en comparación con el carcinoma anal de células escamosas tuvo una supervivencia general inferior a 5 años, etapa por etapa. El adenocarcinoma anal parece tratarse de manera similar al paradigma del cáncer rectal, con el uso frecuente de quimiorradiación neoadyuvante. Vea el video del resumen en http://links.lww.com/DCR/B50.

Impact of socioeconomic status on survival for patients with anal cancer.

BACKGROUND: Although outcomes for patients with squamous cell carcinoma of the anus (SCCA) have improved, the gains in benefit may not be shared uniformly among patients of disparate socioeconomic status. In the current study, the authors investigated whether area-based median household income (MHI) is predictive of survival among patients with SCCA. METHODS: Patients diagnosed with SCCA from 2004 through 2013 in the Surveillance, Epidemiology, and End Results registry were included. Socioeconomic status was defined by census-tract MHI level and divided into quintiles. Multivariable Cox proportional hazards models and logistic regression were used to study predictors of survival and radiotherapy receipt. RESULTS: A total of 9550 cases of SCCA were included. The median age of the patients was 58 years, 63% were female, 85% were white, and 38% were married. In multivariable analyses, patients living in areas with lower MHI were found to have worse overall survival and cancer-specific survival (CSS) compared with those in the highest income areas. Mortality hazard ratios for lowest to highest income were 1.32 (95% confidence interval [95% CI], 1.18-1.49), 1.31 (95% CI, 1.16-1.48), 1.19 (95% CI, 1.06-1.34), and 1.16 (95% CI, 1.03-1.30). The hazard ratios for CSS similarly ranged from 1.34 to 1.22 for lowest to highest income. Older age, black race, male sex, unmarried marital status, an earlier year of diagnosis, higher tumor grade, and later American Joint Committee on Cancer stage of disease also were associated with worse CSS. Income was not found to be associated with the odds of initiating radiotherapy in multivariable analysis (odds ratio of 0.87 for lowest to highest income level; 95% CI, 0.63-1.20). CONCLUSIONS: MHI appears to independently predict CSS and overall survival in patients with SCCA. Black race was found to remain a predictor of SCCA survival despite controlling for income. Further study is needed to understand the mechanisms by which socioeconomic inequalities affect cancer care and outcomes. Cancer 2018;124:1791-7. © 2018 American Cancer Society.

Post-mastectomy Radiation Therapy in Breast Cancer Patients with Nodal Micrometastases.

BACKGROUND: Recent data support the use of post-mastectomy radiation therapy (PMRT) in women with one to three positive lymph nodes; however, the benefit of PMRT in patients with micrometastatic nodal disease (N1mi) is unknown. We evaluated the survival impact of PMRT in patients with N1mi within the National Cancer Database. METHODS: The pattern of care and survival benefit of PMRT was examined in women with pT1-2N1mi breast cancer who underwent mastectomy without neoadjuvant chemotherapy. Univariable and multivariable Cox proportional hazard models were employed for survival analysis, and subanalyses of high-risk patients and a propensity score-matched (PSM) cohort were completed. RESULTS: From 2004 to 2014, we identified 14,019 patients who fitted the study criteria. PMRT was delivered in 18.5% of patients and its use increased over the study period. Patients treated with PMRT were younger, had better performance status and larger primaries, were estrogen receptor (ER)-negative, had higher grade, lymphovascular invasion and positive surgical margins, and more often received systemic therapy. PMRT was significantly associated with overall survival (OS) in univariable analysis (hazard ratio [HR] 0.75 [0.64-0.89]), but was not significant in multivariable analysis (adjusted HR 1.01 [0.84-1.20]). There was no survival benefit to PMRT in ER-negative, high-grade, and/or young patients. There were 2 (0.9%) death events in the sentinel lymph node biopsy (SLNB) + PMRT group versus 21 (2.9%) in the SLNB-alone group (log-rank p = 0.053), and 8 (3.9%) death events in the axillary lymph node biopsy (ALNB) + PMRT group versus 27 (3.6%) in the axillary lymph node dissection-alone group (p = 0.82). There was no significant association between PMRT and OS within the PSM subgroup. CONCLUSION: In this largest reported retrospective study, no OS differences were associated with PMRT, which suggests that PMRT may not benefit every patient with microscopic nodal disease.

Triple-modality treatment in patients with advanced stage tonsil cancer.

BACKGROUND: Concurrent chemoradiation (CCRT) and upfront surgery followed by adjuvant therapy both are recommended treatment options for patients with advanced stage squamous cell carcinoma (SCC) of the tonsil. To the authors' knowledge, the question of whether surgical-based treatments can achieve better survival compared with CCRT has never been compared in a clinical trial. The authors analyzed the National Cancer Data Base to measure the impact of different treatment modalities on overall survival (OS). METHODS: All patients aged ≤70 years diagnosed with clinical stage III to IVB (excluding T4B) SCC of the tonsil from 1998 through 2011 were selected. Analysis was limited to patients receiving CCRT, surgery plus CCRT, or surgery followed by adjuvant radiotherapy (RT). OS was compared using the Kaplan-Meier method and log-rank test. Univariable and multivariable hazards analyses were performed to identify factors significant for survival. Propensity score matching was performed. RESULTS: There were 16,891 patients who met the inclusion criteria. The most common treatment was CCRT (8123 patients; 48.1%), followed by surgery plus CCRT (5249; 31.1%) and surgery plus RT (3519 patients; 20.8%). Patients treated with surgery plus CCRT were found to have the highest 3-year OS rate (88.5%) followed by those treated with surgery plus RT (84%) and CCRT (74.2%) (P<.0001). In a propensity score-matched subpopulation of 4962 patients, the 3-year OS rate was 90.2% for those treated with surgery plus CCRT, 84.9% for those treated with surgery plus RT, and 82.1% for those treated with definitive CCRT (P<.0001). CONCLUSIONS: Patients with advanced stage SCC of the tonsil who underwent surgery followed by CCRT had the greatest OS. Patients undergoing upfront surgery may avoid chemotherapy without jeopardizing survival. Triple-modality therapy may provide a survival benefit for a subset of patients with advanced stage tonsil cancer. Cancer 2017;123:3269-76. © 2017 American Cancer Society.

The Impact of Adjuvant Postoperative Radiation Therapy and Chemotherapy on Survival After Esophagectomy for Esophageal Carcinoma.

OBJECTIVE: The objective of this study was to analyze the impact on overall survival (OS) from the addition of postoperative radiation with or without chemotherapy after esophagectomy, using a large, hospital-based dataset. BACKGROUND: Previous retrospective studies have suggested an OS advantage for postoperative chemoradiation over surgery alone, although prospective data are lacking. METHODS: The National Cancer Data Base was queried to select patients diagnosed with stage pT3-4Nx-0M0 or pT1-4N1-3M0 esophageal carcinoma (squamous cell or adenocarcinoma) from 1998 to 2011 treated with definitive esophagectomy ± postoperative radiation and/or chemotherapy. OS was analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was used to identify covariates associated with OS. RESULTS: There were 4893 patients selected, of whom 1153 (23.6%) received postoperative radiation. Most patients receiving radiation also received sequential/concomitant chemotherapy (89.9%). For the entire cohort, postoperative radiation was associated with a statistically significant but modest absolute improvement in survival (hazard ratio 0.77; 95% CI, 0.71-0.83; P < 0.001). On subgroup analysis, postoperative radiation was associated with improved OS for patients with node-positive disease (3-yr OS 34.3 % vs 27.8%, P < 0.001) or positive margins (3-yr OS 36.4% vs 18.0%, P < 0.001). When chemotherapy usage was incorporated, sequential chemotherapy was associated with the best survival (P < 0.001). Multivariate analysis revealed that the addition of chemotherapy to radiation therapy, whether sequentially or concurrently, was a strong prognostic factor for OS. CONCLUSIONS: In this hospital-based study, the addition of postoperative chemoradiation (either sequentially or concomitantly) after esophagectomy was associated with improved OS for patients with node-positive disease or positive margins.

Patterns of care of IMRT usage in postoperative management of uterine cancer.

OBJECTIVE: To analyze the patterns of care regarding intensity modulated radiation therapy (IMRT) usage in the postoperative management of uterine cancer. METHODS: The National Cancer Database was queried to identify women with endometrial adenocarcinoma who underwent hysterectomy followed by external beam radiation between 2004-2012. Descriptive statistics were used to analyze IMRT usage with comparison via the Chi Square test. Overall survival was also compared between IMRT and three dimensional conformal radiation therapy. Multivariable logistic regression and multivariable Cox Regression were used to identify covariables that impact IMRT usage and improved survival respectively. RESULTS: 7839 women were included in this study. IMRT utilization increased from 1.9% in 2004 to 32.4% in 2012 (p<0.001). The adjusted odds ratio (OR) for IMRT in 2012 compared with 2004 was 24.90, 95% CI 15.24-40.67 (p<0.001). Aside from year, other predictors of IMRT usage on multivariate analysis were positive nodes, higher dose, private insurance and higher income. Black race was associated with lower IMRT usage compared to Whites with an OR of 0.60, 95% CI 0.44-0.81 (p=0.001). IMRT was not associated with significantly increased survival (HR 0.86, 95% CI 0.73-1.01, p=0.06). Black race and positive nodes were associated with decreased survival within the group studied whereas private insurance and higher income were associated with improved survival. CONCLUSIONS: In this hospital-based registry, IMRT has significantly increased in utilization for postoperative radiation in uterine cancer between 2004-2012 although not resulting in significantly improved survival. Socioeconomic and racial disparities exist in the allocation of IMRT usage.

Patterns of adjuvant radiation usage and survival outcomes for stage I endometrial carcinoma in a large hospital-based cohort.

OBJECTIVE: Two randomized trials have demonstrated a local control advantage in the absence of a survival advantage for the addition of adjuvant radiation therapy (RT) to surgery in patients with stage I endometrial adenocarcinoma (EC). This study analyzed the National Cancer Data Base (NCDB) to evaluate the impact of adjuvant RT on overall survival (OS) for patients with stage I EC. METHODS: Patients with EC who underwent total hysterectomy/bilateral salpingo-oophorectomy between 2004 and 2011 were queried. Only those with AJCC stage pT1N0M0 were included. Patients surviving <4months excluded. Adjuvant RT included external beam RT (EBRT), brachytherapy, or external RT+brachytherapy. OS was analyzed using the Kaplan-Meier method. Multivariate Cox regression analysis and propensity matched analysis were performed to assess the impact of covariates on OS. RESULTS: There were 61,697 patients included. Most women (83.9%) did not receive adjuvant RT. Adjuvant RT usage increased with increasing stage/grade. Usage of brachytherapy alone decreased with increasing stage/grade (78.2% for IA/G1 to 36.1% for IB/G3) corresponding to an increase in the use of EBRT (21.8% for IA/G1 to 53.9% for IB/G3). On multivariable analysis, adjuvant EBRT (HR 0.83, 95%CI 0.74-0.93, p=0.002) and brachytherapy (HR 0.82, 95%CI 0.74-0.93, p=0.002) were each associated with improved survival for women with stage IB. In the propensity matched cohort, RT was associated with improved survival (0.85, 95% CI 0.78-0.92, p<0.001). CONCLUSION: The use of adjuvant RT for women with stage I EC is highly dependent on stage/grade and is associated with improved survival for stage IB.

A Comparison of Outcomes Between Open Hysterectomy and Robotic-Assisted Hysterectomy for Endometrial Cancer Using the National Cancer Database.

PURPOSE: The purpose of this study is to evaluate usage patterns and outcomes of women who underwent open hysterectomy (OH) versus robotic assisted-hysterectomy (RAH) for the treatment of endometrial cancer. METHODS: Women with nonmetastatic endometrial adenocarcinoma diagnosed between 2010 and 2012, who either underwent an OH or RAH, were selected from the National Cancer Database. The χ, Fisher exact, or Mann-Whitney U tests were used where appropriate to compare outcomes between groups. Multivariable logistic regression was used to analyze for predictors for RAH and other outcome variables. RESULTS: A total of 43,985 women were included in this study with a median age of 61 years. Of these, 23,872 (54.3%) underwent RAH and 20,113 (45.7%) underwent OH. The usage of RAH increased from 43.0% in 2010 to 63.8% in 2012 (P < 0.001). Women receiving RAH were more commonly found to have a Charlson comorbidity score of 0 to 1, lower pathologic stage, nonblack race, treatment at a comprehensive center, and had insurance other than Medicaid. Robotic-assisted hysterectomy was associated with a shorter inpatient stay, lower readmission rates, and lower 30- and 90-day mortality rates (P < 0.001 for all comparisons). There was a significant improvement in overall survival favoring RAH, 96.1% versus 94.0%, which persisted on multivariable logistic regression (P < 0.001). CONCLUSIONS: In this large, hospital-based analysis, RAH was associated with decreased length of stay, lower readmission rates, and less perioperative mortality. However, socioeconomic status continues to remain a barrier to equal treatment allocation. Overall survival was improved with RAH, but the follow-up is limited, and this finding must be interpreted with caution.

Use of Adjuvant Chemotherapy, Radiation Therapy, or Combined Modality Therapy and the Impact on Survival for Uterine Carcinosarcoma Limited to the Pelvis.

OBJECTIVE: Clinical outcomes for patients with uterine carcinosarcoma are poor after surgical management alone. Adjuvant therapies including chemotherapy (CT) and/or radiation therapy (RT) have been previously investigated, but the optimal management of this disease remains controversial. The purposes of this study were to analyze the patterns of use of adjuvant CT and RT and to assess the impact on survival of each of these treatment regimens using the National Cancer Data Base. METHODS/MATERIALS: The National Cancer Data Base was queried for patients given a diagnosis of uterine carcinosarcoma confined to the pelvis who underwent total hysterectomy/bilateral salpingo-oophorectomy between 2004 and 2011. Patients were excluded if they survived less than 4 months after diagnosis. Data regarding CT and RT use were collected. Overall survival (OS) was analyzed using the Kaplan-Meier method. Multivariable Cox regression analysis was performed to evaluate the effect of covariates on OS. RESULTS: A total of 4906 patients were included in this study. Median age was 67 years (interquartile range, 60-75 years). Median follow-up was 28.9 months (interquartile range, 15.4-52.9 months). There were 1777 patients (36.2%) who received no adjuvant treatment, 971 (19.8%) who received CT alone, 1060 (21.6%) who received RT alone, and 1098 (22.4%) who received both RT and CT. The 5-year OS for patients receiving no adjuvant therapy, adjuvant RT alone, adjuvant CT alone, and combined CT and RT were 44.9%, 47.1%, 47.5%, and 62.9%, respectively. On pairwise analysis, combined CT and RT was associated with improved survival compared with all other subgroups (P < 0.001). On multivariable Cox regression analysis, combined CT and RT (hazard ratio, 0.50; 95% confidence interval, 0.44-0.57; P < 0.001) and CT alone (hazard ratio, 0.78; 95% confidence interval, 0.69-0.88; P < 0.001) were significantly associated with improved OS, whereas RT alone was not. CONCLUSIONS: Combination therapy with CT and RT was associated with significantly improved 5-year OS compared with no further therapy, RT alone, or CT alone.

Patterns of care and survival outcomes in the treatment of esophageal melanoma.

Because of the rarity of esophageal melanoma, the optimal management of this disease is limited. The pooled dataset in the National Cancer Database (NCDB) was used to identify the prognostic factors and treatment outcomes. Patients who were diagnosed with esophageal melanoma between 2004 and 2011 were identified. Patients were stratified as either localized (T1-4N0M0), regional (T1-4N+M0), or metastatic (M1). The primary endpoint of this study was overall survival (OS) which was analyzed using the Kaplan-Meier method and multivariate Cox regression, which was performed to identify potential factors influencing survival. A total of 56 patients were identified with median follow-up of 10.2 months. Twenty-seven (48.2%) patients had localized disease, 10 patients (17.9%) had regional disease, and 19 patients (33.9%) were metastatic at diagnosis. For those with localized disease, the 3 year OS was 50.5% for the 14 patients treated with esophagectomy, and 0.0% for the seven treated with definitive radiation therapy. For regional disease, the 3 year OS was 11.1% for the nine patients treated with esophagectomy. The 3 year OS for those with metastatic disease at diagnosis was 0.0%. On multivariate analysis, treatment with esophagectomy was not associated with a reduced risk of death (HR 0.84, 95% CI 0.31-2.25, P = 0.73), while regional disease (HR 3.78, 95% CI 1.40-10.19, P = 0.009) and metastatic disease (HR 7.54, 95% CI 2.89-19.62, P < 0.001) were associated with decreased survival. Esophageal melanoma is an extremely rare and aggressive disease with very poor outcomes. Esophagectomy may result in reasonable survival for localized disease.

Treatment and survival outcomes of small cell carcinoma of the esophagus: an analysis of the National Cancer Data Base.

Given the paucity of esophageal small cell carcinoma (SCC) cases, there are few large studies evaluating this disease. In this study, the National Cancer Data Base (NCDB) was utilized to analyze the clinical features, treatment, and survival of patients with esophageal SCC in a large, population-based dataset. We selected patients diagnosed with esophageal SCC from 1998 to 2011. Patients were identified as having no treatment, chemotherapy alone, radiation ± sequential chemotherapy, concurrent chemoradiation, and esophagectomy ± chemotherapy and/or radiation. Overall survival (OS) was analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was conducted to identify factors associated with OS. A total of 583 patients were identified. Most patients had stage IV disease (41.7%). Regarding treatment selection, chemoradiation was the most commonly utilized for patients with nonmetasatic disease, whereas chemotherapy alone was most common for metastatic patients. Esophagectomy (median survival 44.9 months with 3 year OS 50.5%) was associated with the best OS for patients with localized (node-negative) disease compared with chemotherapy alone (p < 0.001) or chemoradiation (p = 0.01). For locoregional (node-positive) disease, treatment with chemoradiation resulted in a median survival of 17.8 months and a 3 year OS 31.6%. On multivariate analysis, treatment with chemotherapy alone (p = 0.003) was associated with worse OS while esophagectomy (p = 0.04) was associated with improved OS compared to chemoradiation. Esophageal SCC is an aggressive malignancy with most patients presenting with metastatic disease. Either esophagectomy or chemoradiation as part of multimodality treatment appear to improve OS for selected patients with nonmetastatic disease.

The Relationship of Baseline Prostate Specific Antigen and Risk of Future Prostate Cancer and Its Variance by Race.

PURPOSE: Several studies suggest that a baseline prostate specific antigen (PSA) measured in young men predicts future risk of prostate cancer. Considering recent recommendations against PSA screening, high-risk populations (e.g. black men, men with a high baseline PSA) may be particularly vulnerable in the coming years. Thus, we investigated the relationship between baseline PSA and future prostate cancer in a black majority-minority urban population. MATERIALS AND METHODS: A retrospective analysis was performed of the prostate biopsy database (n = 994) at the Brooklyn Veterans Affairs Hospital. These men were referred to urology clinic for elevated PSA and biopsied between 2007 and 2014. Multivariate logistic regression was used to predict positive prostate biopsy from log-transformed baseline PSA, race (black, white, or other), and several other variables. RESULTS: The majority of men identified as black (50.2%). Median age at time of baseline PSA and biopsy was 58.6 and 64.8, respectively. Median baseline PSA was similar among black men and white men (2.70 vs 2.91 for black men vs white men, p = 0.232). Even so, black men were more likely than white men to be diagnosed with prostate cancer (OR 1.62, p < 0.0001). Black men less than age 70 were at particularly greater risk than their white counterparts. Baseline PSA was not a statistically significant predictor of future prostate cancer (p = 0.101). CONCLUSIONS: Black men were more likely to be diagnosed with prostate cancer than were white men, despite comparable baseline PSA. In our pre-screened population at the urology clinic, a retrospective examination of baseline PSA did not predict future prostate cancer.

Utilization of adjuvant therapies and their impact on survival for women with stage IIIC endometrial adenocarcinoma.

PURPOSE/OBJECTIVES: Adjuvant treatment options following surgical staging for women with stage IIIC endometrial carcinoma include chemotherapy (CT) with or without radiation therapy (RT). We utilized the National Cancer Database (NCDB) to investigate utilization of adjuvant CT and RT for this group of patients and assess their impact on overall survival (OS). MATERIALS/METHODS: The NCDB was queried for patients diagnosed with non-metastatic surgically staged uterine adenocarcinoma between 2004 and 2011 with at least one pathologically positive lymph node. Overall survival (OS) was analyzed using the Kaplan-Meier method. Comparison was made between patients receiving no additional therapy, RT alone, CT alone, or a combination of CT and RT (CMT). Multivariable cox regression analysis (MVA) was performed to evaluate the effect of covariates on OS. RESULTS: A total of 6720 patients were included in this study. Of whom, 1409 received no adjuvant treatment, 1533 received CT only, 1265 received RT only, and 2522 received CMT. The 5-year OS for patients receiving no adjuvant therapy, RT alone, CT alone, and CMT were 54.9%, 63.9%, 64.4%, and 72.6%, respectively. On pairwise analysis, CMT was associated with improved survival compared to all other subgroups (p<0.001). On MVA, CMT (HR 0.58, 95% CI 0.52-0.66, p<0.001) was the strongest predictor for improved OS compared to RT alone (HR 0.79, 95% CI 0.69-0.89, p<0.001) or CT alone (HR 0.75, 95% CI 0.66-0.85, p<0.001). CONCLUSIONS: Both adjuvant CT and adjuvant RT were associated with improved OS for women with stage IIIC endometrial adenocarcinoma, but CMT was associated with the largest improvement in OS.

Targeting the colony stimulating factor 1 receptor alleviates two forms of Charcot-Marie-Tooth disease in mice.

See Scherer (doi:10.1093/awv279) for a scientific commentary on this article.Charcot-Marie-Tooth type 1 neuropathies are inherited disorders of the peripheral nervous system caused by mutations in Schwann cell-related genes. Typically, no causative cure is presently available. Previous preclinical data of our group highlight the low grade, secondary inflammation common to distinct Charcot-Marie-Tooth type 1 neuropathies as a disease amplifier. In the current study, we have tested one of several available clinical agents targeting macrophages through its inhibition of the colony stimulating factor 1 receptor (CSF1R). We here show that in two distinct mouse models of Charcot-Marie-Tooth type 1 neuropathies, the systemic short- and long-term inhibition of CSF1R by oral administration leads to a robust decline in nerve macrophage numbers by ∼70% and substantial reduction of the typical histopathological and functional alterations. Interestingly, in a model for the dominant X-linked form of Charcot-Marie-Tooth type 1 neuropathy, the second most common form of the inherited neuropathies, macrophage ablation favours maintenance of axonal integrity and axonal resprouting, leading to preserved muscle innervation, increased muscle action potential amplitudes and muscle strengths in the range of wild-type mice. In another model mimicking a mild, demyelination-related Charcot-Marie-Tooth type 1 neuropathy caused by reduced P0 (MPZ) gene dosage, macrophage blockade causes an improved preservation of myelin, increased muscle action potential amplitudes, improved nerve conduction velocities and ameliorated muscle strength. These observations suggest that disease-amplifying macrophages can produce multiple adverse effects in the affected nerves which likely funnel down to common clinical features. Surprisingly, treatment of mouse models mimicking Charcot-Marie-Tooth type 1A neuropathy also caused macrophage blockade, but did not result in neuropathic or clinical improvements, most likely due to the late start of treatment of this early onset disease model. In summary, our study shows that targeting peripheral nerve macrophages by an orally administered inhibitor of CSF1R may offer a highly efficacious and safe treatment option for at least two distinct forms of the presently non-treatable Charcot-Marie-Tooth type 1 neuropathies.

In-feed supplementation of trans-cinnamaldehyde reduces layer-chicken egg-borne transmission of Salmonella enterica serovar enteritidis.

Salmonella enterica serovar Enteritidis is a major foodborne pathogen in the United States, causing gastroenteritis in humans, primarily through consumption of contaminated eggs. Chickens are the reservoir host of S. Enteritidis. In layer hens, S. Enteritidis colonizes the intestine and migrates to various organs, including the oviduct, leading to egg contamination. This study investigated the efficacy of in-feed supplementation with trans-cinnamaldehyde (TC), a generally recognized as safe (GRAS) plant compound obtained from cinnamon, in reducing S. Enteritidis cecal colonization and systemic spread in layers. Additionally, the effect of TC on S. Enteritidis virulence factors critical for macrophage survival and oviduct colonization was investigated in vitro. The consumer acceptability of eggs was also determined by a triangle test. Supplementation of TC in feed for 66 days at 1 or 1.5% (vol/wt) for 40- or 25-week-old layer chickens decreased the amounts of S. Enteritidis on eggshell and in yolk (P<0.001). Additionally, S. Enteritidis persistence in the cecum, liver, and oviduct in TC-supplemented birds was decreased compared to that in controls (P<0.001). No significant differences in feed intake, body weight, or egg production in birds or in consumer acceptability of eggs were observed (P>0.05). In vitro cell culture assays revealed that TC reduced S. Enteritidis adhesion to and invasion of primary chicken oviduct epithelial cells and reduced S. Enteritidis survival in chicken macrophages (P<0.001). Follow-up gene expression analysis using real-time quantitative PCR (qPCR) showed that TC downregulated the expression of S. Enteritidis virulence genes critical for chicken oviduct colonization (P<0.001). The results suggest that TC may potentially be used as a feed additive to reduce egg-borne transmission of S. Enteritidis.

Reduction of Salmonella enterica serovar enteritidis colonization in 20-day-old broiler chickens by the plant-derived compounds trans-cinnamaldehyde and eugenol.

The efficacies of trans-cinnamaldehyde (TC) and eugenol (EG) for reducing Salmonella enterica serovar Enteritidis colonization in broiler chickens were investigated. In three experiments for each compound, 1-day-old chicks (n = 75/experiment) were randomly assigned to five treatment groups (n = 15/treatment group): negative control (-ve S. Enteritidis, -ve TC, or EG), compound control (-ve S. Enteritidis, +ve 0.75% [vol/wt] TC or 1% [vol/wt] EG), positive control (+ve S. Enteritidis, -ve TC, or EG), low-dose treatment (+ve S. Enteritidis, +ve 0.5% TC, or 0.75% EG), and high-dose treatment (+ve S. Enteritidis, +ve 0.75% TC, or 1% EG). On day 0, birds were tested for the presence of any inherent Salmonella (n = 5/experiment). On day 8, birds were inoculated with ∼8.0 log(10) CFU S. Enteritidis, and cecal colonization by S. Enteritidis was ascertained (n = 10 chicks/experiment) after 24 h (day 9). Six birds from each treatment group were euthanized on days 7 and 10 after inoculation, and cecal S. Enteritidis numbers were determined. TC at 0.5 or 0.75% and EG at 0.75 or 1% consistently reduced (P < 0.05) S. Enteritidis in the cecum (≥3 log(10) CFU/g) after 10 days of infection in all experiments. Feed intake and body weight were not different for TC treatments (P > 0.05); however, EG supplementation led to significantly lower (P < 0.05) body weights. Follow-up in vitro experiments revealed that the subinhibitory concentrations (SICs, the concentrations that did not inhibit Salmonella growth) of TC and EG reduced the motility and invasive abilities of S. Enteritidis and downregulated expression of the motility genes flhC and motA and invasion genes hilA, hilD, and invF. The results suggest that supplementation with TC and EG through feed can reduce S. Enteritidis colonization in chickens.