Cure models with adaptive activation for modeling cancer survival.

We propose a class of cure rate models motivated by analysis of colon cancer and triple-negative breast cancer survival data. This class is indexed by an adaptive activation parameter and a function. We establish that the class is stochastically ordered in the activation parameter and also establish two identifiability results for this class. The first- and last-activation models are members of this class whereas many cure rate models proposed in the literature are also part of this class. We illustrate that while first- and last-activation models may perform poorly under model misspecifications, the proposed model with adaptive activation provides appropriate inference in these cases. We apply the proposed approach to assess treatment-sex interaction on cure rate in a colon cancer study and to assess role of tumor heterogeneity and ethnic disparity in breast cancer.

COVID-19 Vaccine Policy Implementation and Differential Vaccine Uptake Trajectories in Chicago Communities.

BACKGROUND: Since the onset of the COVID-19 pandemic, multiple public health interventions have been implemented to respond to the rapidly evolving pandemic and community needs. This article describes the scope, timing, and impact of coordinated strategies for COVID-19 vaccine uptake in Chicago for the first year of vaccine distribution. METHODS: Using a series of interviews with public health officials and leaders of community-based organizations (CBOs) who participated in the implementation of the citywide COVID-19 vaccine outreach initiatives, we constructed a timeline of vaccine outreach initiatives. The timeline was matched to the vaccine uptake rates to explore the impact of the vaccine outreach initiatives by community area. Finally, we discussed the nature of policy initiatives and the level of vaccine uptake in relation to community characteristics. RESULTS: The Chicago Department of Public Health (CDPH) implemented myriad vaccine outreach strategies, including mass vaccination sites, improved access, and community-level vaccine campaigns. Protect Chicago+ was the primary vaccine outreach effort initiated by the CDPH, which identified 15 highly vulnerable community areas. More than 2.7 million (67%) Chicagoans completed the vaccine regimen by December 2021. Black (51.3%) Chicagoans were considerably less likely to be vaccinated than Asian (77.6%), White (69.8%), and Hispanic (63.6%) Chicago residents. In addition, there were significant spatial differences in the rate of COVID-19 vaccine completion: predominantly White and Hispanic communities, compared with Black communities, had higher rates of vaccine completion. CONCLUSIONS: The community outreach efforts to improve COVID-19 vaccine uptake in Chicago have shown the importance of community-engaged approaches in pandemic responses. Despite citywide efforts to build community infrastructure, Black communities had relatively lower levels of vaccine uptake than other communities. Broader social restructuring to mitigate disinvestment and residential segregation and to ameliorate medical mistrust will be needed to prepare for future pandemics and disasters.

A Hybrid Effectiveness/Implementation Clinical Trial of Adherence to Long-Term Oxygen Therapy for Chronic Obstructive Pulmonary Disease.

Rationale: Interventions to promote adherence to long-term oxygen therapy (LTOT) in chronic obstructive pulmonary disease (COPD) are needed. Objectives: To examine the real-world effectiveness of phone-based peer coaching on LTOT adherence and other outcomes in a pragmatic trial of patients with COPD. Methods: In a hybrid effectiveness/implementation pragmatic trial, patients were randomized to receive phone-based proactive coaching (educational materials, five phone-based peer coaching sessions over 60 d), reactive coaching (educational materials, peer coaching when requested), or usual care. Study staff members collected baseline and outcome data via phone at 30, 60, and 90 days after randomization. Adherence to LTOT over 60 days, the primary effectiveness outcome, was defined as mean LTOT use ⩾17.7 h/d. LTOT use was calculated using information about home oxygen equipment use in worksheets completed by study participants. Comparisons of adherence to LTOT between each coaching group and the usual care group using multivariable logistic regression models were prespecified as the primary analyses. Secondary effectiveness outcomes included Patient Reported Outcome Management Information System measures for physical, emotional, and social health. We assessed early implementation domains in the reach, adoption, and implementation framework. Results: In 444 participants, the proportions who were adherent to LTOT at 60 days were 74% in usual care, 84% in reactive coaching, and 70% in proactive coaching groups. Although reach, adoption by stakeholder partners, and intervention fidelity were acceptable, complete LTOT adherence data were available in only 73% of participants. Reactive coaching (adjusted odds ratio, 1.77; 97.5% confidence interval, 0.80-3.90) and proactive coaching (adjusted odds ratio, 0.70; 97.5% confidence interval, 0.34-1.46) did not improve adherence to LTOT compared with usual care. However, proactive coaching significantly reduced depressive symptoms and sleep disturbance compared with usual care and reduced depressive symptoms compared with reactive coaching. Unexpectedly, LTOT adherence was significantly lower in the proactive compared with the reactive coaching group. Conclusions: The results were inconclusive about whether a phone-based peer coaching strategy changed LTOT adherence compared with usual care. Further studies are needed to confirm the potential benefits of proactive peer coaching on secondary effectiveness outcomes and differences in LTOT adherence between proactive and reactive peer coaching. Clinical trial registered with ClinicalTrials.gov (NCT02098369).

Bayesian functional data analysis over dependent regions and its application for identification of differentially methylated regions.

We consider a Bayesian functional data analysis for observations measured as extremely long sequences. Splitting the sequence into several small windows with manageable lengths, the windows may not be independent especially when they are neighboring each other. We propose to utilize Bayesian smoothing splines to estimate individual functional patterns within each window and to establish transition models for parameters involved in each window to address the dependence structure between windows. The functional difference of groups of individuals at each window can be evaluated by the Bayes factor based on Markov Chain Monte Carlo samples in the analysis. In this paper, we examine the proposed method through simulation studies and apply it to identify differentially methylated genetic regions in TCGA lung adenocarcinoma data.

Development of a Novel Circulating Autoantibody Biomarker Panel for the Identification of Patients with 'Actionable' Pulmonary Nodules.

Due to poor compliance and uptake of LDCT screening among high-risk populations, lung cancer is often diagnosed in advanced stages where treatment is rarely curative. Based upon the American College of Radiology's Lung Imaging and Reporting Data System (Lung-RADS) 80-90% of patients screened will have clinically "non-actionable" nodules (Lung-RADS 1 or 2), and those harboring larger, clinically "actionable" nodules (Lung-RADS 3 or 4) have a significantly greater risk of lung cancer. The development of a companion diagnostic method capable of identifying patients likely to have a clinically actionable nodule identified during LDCT is anticipated to improve accessibility and uptake of the paradigm and improve early detection rates. Using protein microarrays, we identified 501 circulating targets with differential immunoreactivities against cohorts characterized as possessing either actionable (n = 42) or non-actionable (n = 20) solid pulmonary nodules, per Lung-RADS guidelines. Quantitative assays were assembled on the Luminex platform for the 26 most promising targets. These assays were used to measure serum autoantibody levels in 841 patients, consisting of benign (BN; n = 101), early-stage non-small cell lung cancer (NSCLC; n = 245), other early-stage malignancies within the lung (n = 29), and individuals meeting United States Preventative Screening Task Force (USPSTF) screening inclusion criteria with both actionable (n = 87) and non-actionable radiologic findings (n = 379). These 841 patients were randomly split into three cohorts: Training, Validation 1, and Validation 2. Of the 26 candidate biomarkers tested, 17 differentiated patients with actionable nodules from those with non-actionable nodules. A random forest model consisting of six autoantibody (Annexin 2, DCD, MID1IP1, PNMA1, TAF10, ZNF696) biomarkers was developed to optimize our classification performance; it possessed a positive predictive value (PPV) of 61.4%/61.0% and negative predictive value (NPV) of 95.7%/83.9% against Validation cohorts 1 and 2, respectively. This panel may improve patient selection methods for lung cancer screening, serving to greatly reduce the futile screening rate while also improving accessibility to the paradigm for underserved populations.

Lipidomics, Acute Ischemic Stroke, Symptoms, and Outcomes: Observational Study Protocol.

BACKGROUND: Acute ischemic stroke is one of the leading causes of death and disability globally. Recent advances in omics methodology enable lipidomic profiling, which may provide knowledge of the underlying pathology of acute ischemic stroke and its associated outcomes. OBJECTIVE: This study aims to examine the longer-term relationships between symptoms and outcomes following acute ischemic stroke and the underlying lipidomic signatures over 6 months during recovery between acute ischemic stroke patients who received reperfusion therapies and those who did not. METHODS: This prospective cohort study will enroll 104 participants post-acute ischemic stroke in two groups based on their receipt of reperfusion therapy (Group 1) or not (Group 2; n = 52/group). Peripheral plasma samples will be collected from both groups for lipidomic analysis over 6 months. Arterial blood samples will be collected during the procedure for those receiving reperfusion. Self-reported symptoms and outcome data will be collected from both groups. DISCUSSION: We will compare and examine the associations among plasma lipidomic biomarkers and symptoms and cognitive, functional, and health-related quality of life outcomes over 6 months between acute ischemic stroke patients who did and did not receive reperfusion intervention.

Expression of CISH, an Inhibitor of NK Cell Function, Increases in Association with Ovarian Cancer Development and Progression.

Epithelial ovarian cancer (OVCA), a fatal malignancy of women, disseminates locally. Although NK cells mount immune responses against OVCA, tumors inhibit NK cells, and the mechanism is not well understood. Cytokines stimulate NK cells; however, chronic stimulation exhausts them and induces expression of cytokine-inducible SH2-containing protein (CISH). Tumors produce anti-inflammatory cytokine interleukin (IL)-10 which may induce NK cell exhaustion. The goal of this study was to examine if CISH expression in NK cells increases during OVCA development and to determine the mechanism(s) of OVCA-induced CISH expression in NK cells. Normal ovaries (n = 7) were used for CISH, IL-10 and GRP78 expression. In tumor ovaries, CISH was examined in early and late stages (n = 14 each, all subtypes) while IL-10 and GRP78 expression were examined in early and late stage HGSC (n = 5 each). Compared to normal, the population of CISH-expressing NK cells increased and the intensity of IL-10 and GRP78 expression was significantly higher in OVCA (p < 0.05). CISH expression was positively correlated with IL-10 expression (r = 0.52, r = 0.65, p < 0.05 at early and late stages, respectively) while IL-10 expression was positively correlated with GRP78 expression (r = 0.43, r = 0.52, p < 0.05, respectively). These results suggest that OVCA development and progression are associated with increased CISH expression by NK cells which is correlated with tumor-induced persistent cellular stress.

Glucose-Regulated Protein 78 Is a Potential Serum and Imaging Marker for Early Detection of Ovarian Cancer.

BACKGROUND: Understanding malignant transformation associated with ovarian cancer (OVCA) is important to establish early detection tests. This study examined whether expression of glucose-regulated protein 78 (GRP78, marker of cellular stress) increases during OVCA development, and whether GRP78 can be detected by targeted-transvaginal ultrasound (TVUS) imaging. METHODS: Normal ovaries (n = 10), benign (n = 10) and malignant ovarian tumors at early (n = 8) and late stages (n = 16), hens with and without ovarian tumors at early and late stages (n = 10, each) were examined for GRP78 expression during OVCA development by immunohistochemistry, immunoblotting, gene expression and immunoassay. Feasibility of GRP78-targeted TVUS imaging in detecting early OVCA was examined. RESULTS: Compared with normal ovaries and benign tumors, intensity of GRP78 expression was higher (p < 0.0001) in OVCA patients. Compared with normal (9007.76 ± 816.54 pg/mL), serum GRP78 levels were significantly higher (p < 0.05) in patients with early (12,730.59 ± 817.35 pg/mL) and late-stage OVCA (13,930.12 ± 202.35) (p < 0.01). Compared with normal (222.62 ± 181.69 pg/mL), serum GRP78 levels increased (p < 0.05) in hens with early (590.19 ± 198.18 pg/mL) and late-stage OVCA (1261.38 ± 372.85) (p < 0.01). Compared with non-targeted, GRP78-targeted imaging enhanced signal intensity of TVUS (p < 0.0001). CONCLUSIONS: Tissue and serum levels of GRP78 increase in association with OVCA. GRP78 offers a potential serum and imaging marker for early OVCA detection.

Changes in Nucleolin Expression during Malignant Transformation Leading to Ovarian High-Grade Serous Carcinoma.

OBJECTIVE: Ovarian high-grade serous carcinoma (HGSC) is a fatal malignancy of women. Alterations in the expression of nuclear proteins are early steps in malignant transformation; nucleolin is one such protein. Changes in nucleolin expression and circulatory levels during ovarian HGSC development are unknown. The study goal was to determine if tissue and circulatory levels of nucleolin change in response to malignant transformation leading to ovarian HGSC. METHODS: Sera, ovaries, and BRCA+ fimbria from healthy subjects, and sera and tumor tissues from patients (n = 10 each), and healthy hens and hens with HGSC were examined in exploratory and prospective studies for nucleolin expression by immunohistochemistry, immunoblotting, gene expression, and immunoassay, and analyzed by analysis of variance (ANOVA). RESULTS: Compared with normal, nucleolin expression was higher in patients and hens with ovarian HGSC and in women with a risk of HGSC (P < 0.05). Compared with normal (1400 + 105 pg/mL, n = 8), serum nucleolin levels were 1.5 and 1.7-fold higher in patients with early- (n = 5) and late-stage (n = 5) HGSC, respectively. Additionally, serum nucleolin levels increased significantly (P < 0.05) prior to the formation of detectable masses. CONCLUSION: This pilot study concluded that tissue and serum levels of nucleolin increase in association with malignant changes in ovaries and fimbriae leading to ovarian HGSC.

Predicting Non-home Discharge After Lung Surgery: Analysis of the General Thoracic Surgery Database.

BACKGROUND: Anticipating the need for non-home discharge (NHD) enables improved patient counseling and expedites placement, potentially reducing length of stay and hospital readmission. The objective of this study was to create a simple, preoperative, clinical prediction tool for NHD using The Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTSD). METHODS: The STS GTSD was queried for patients who underwent elective anatomic lung cancer resection between 2009 and 2019. Exclusion criteria included age <18 years, percentage predicted diffusion capacity of the lung for carbon monoxide <20% or >150%, N3 or M1 disease, incomplete datasets, and mortality. The primary outcome was defined as discharge to an extended care, transitional care, rehabilitation center, or another hospital. Multivariable logistic regression was used to select risk factors and a nomogram for predicting risk of NHD was developed. The approach was cross-validated in 100 replications of a training set consisting of randomly selected two-thirds of the cohort and a validation set of remaining patients. RESULTS: A total of 35 948 patients from the STS GTSD met inclusion criteria. Final model variables used to derive the nomogram for NHD risk prediction included age (P < .001), percentage predicted diffusion capacity of the lung for carbon monoxide (P < .001), open surgery (P < .001), cerebrovascular history (P < .001), and Zubrod score (P < .001). The receiver operating characteristic curve, using sensitivities and specificities of the model, yielded area under the curve of 0.74. In 100 replicated cross-validations, out-of-sample area under the curve ranged from 0.72-0.76. CONCLUSIONS: Using readily available preoperative variables, our nomogram prognosticates the risk of NHD after anatomic lung resection with good discriminatory ability. Such risk stratification can enable improved patient counseling and facilitate better planning of patients' postoperative needs.

Conditional survival analysis of patients with resected non-small cell lung cancer.

Background: Conditional survival (CS) analyses provide an estimate of survival accounting for years already survived after treatment. We aim to evaluate the difference between actuarial and conditional survival in patients following lung resection for non-small cell lung cancer (NSCLC). In addition, CS analyses are used to examine whether prognosticators of survival change over time following surgery. Methods: Patients who underwent anatomic lung resection at a single institution for pathologic stage I-IIIA NSCLC between 2010 and 2021 were identified; those who underwent wedge resection for node-negative tumors ≤2 cm were also included. CS estimates were calculated as the probability of remaining disease-free after x years of nonrecurrence (CSx). Kaplan-Meier, log-rank, and Cox proportional hazard methods for examining CS were used for subgroup comparisons and assessing associations with baseline covariates. Results: Overall, 863 patients met the study inclusion criteria, with a median follow-up of 44.1 months. Conditional overall survival (OS) and disease-free survival (DFS) were greater than actuarial rates at all time points after surgery. At the time of resection, male sex (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.03 to 1.72; P = .032), tumor size >3 cm (HR, 1.17; 95% CI, 1.11-1.23; P < .001), node positivity (HR, 3.31; 95% CI, 2.52-4.33; P < .001), and American Joint Committee on Cancer stage (P < .001) were associated with DFS. However, if a patient lived 3 years without recurrence (CS3), these factors were no longer prognostic of DFS. Conclusions: Conditional survival analyses provide dynamic assessments of OS and DFS after NSCLC resection. After 3 years without recurrence, certain characteristics associated with DFS at the time of surgery no longer prognosticate recurrence.

Detection of Cannabinoid Receptor Expression by Endometriotic Lesions in Women with Endometriosis as an Alternative to Opioid-Based Pain Medication.

Emerging information suggests a potential role of medicinal cannabis in pain medication in addition to enhancing immune functions. Endometriosis is a disease of women of reproductive age associated with infertility and reproductive failure as well as chronic pain of varying degrees depending on the stage of the disease. Currently, opioids are being preferred over nonsteroidal anti-inflammatory drugs (NSAID) due to the latter's side effects. However, as the opioids are becoming a source of addiction, additional pain medication is urgently needed. Cannabis offers an alternative therapy for treating the pain associated with endometriosis. Information on the use and effectiveness of cannabis against endometriotic pain is lacking. Moreover, expression of receptors for endocannabinoids by the ovarian endometriotic lesions is not known. The goal of this study was to examine whether cannabinoid receptors 1 and 2 (CB1 and CB2) are expressed by ovarian endometriotic lesions. Archived normal ovarian tissues, ovaries with endometriotic lesions, and normal endometrial tissues were examined for the presence of endometrial stromal cells using CD10 (a marker of endometrial stromal cells). Expression of CB1 and CB2 were determined by immunohistochemistry, immunoblotting, and gene expression studies. Intense expression for CB1 and CB2 was detected in the epithelial cells in ovarian endometriotic lesions. Compared with stroma in ovaries with endometriotic lesions, the expression of CB1 and CB2 was significantly higher in the epithelial cells in endometriotic lesions in the ovary (P < 0.0001 and P < 0.05, respectively). Immunoblotting and gene expression assays showed similar patterns for CB1 and CB2 protein and CNR1 (gene encoding CB1) and CNR2 (gene encoding CB2) gene expression. These results suggest that ovarian endometriotic lesions express CB1 and CB2 receptors, and these lesions may respond to cannabinoids as pain medication. These results will form a foundation for a clinical study with larger cohorts.

Conversion of non-inferiority margin from hazard ratio to restricted mean survival time difference using data from multiple historical trials.

The restricted mean survival time measure has gained a lot of interests for designing and analyzing oncology trials with time-to-event endpoints due to its intuitive clinical interpretation and potentially high statistical power. In the non-inferiority trial literature, restricted mean survival time has been used as an alternative measure for reanalyzing a completed trial, which was originally designed and analyzed based on traditional proportional hazard model. However, the reanalysis procedure requires a conversion from the non-inferiority margin measured in hazard ratio to a non-inferiority margin measured by restricted mean survival time difference. An existing conversion method assumes a Weibull distribution for the population survival time of the historical active control group under the proportional hazard assumption using data from a single trial. In this article, we develop a methodology for non-inferiority margin conversion when data from multiple historical active control studies are available, and introduce a Kaplan-Meier estimator-based method for the non-inferiority margin conversion to relax the parametric assumption. We report extensive simulation studies to examine the performances of proposed methods under the Weibull data generative models and a piecewise-exponential data generative model that mimic the tumor recurrence and survival characteristics of advanced colon cancer. This work is motivated to achieve non-inferiority margin conversion, using historical patient-level data from a large colon cancer clinical database, to reanalyze an internationally collaborated non-inferiority study that evaluates 6-month versus 3-month duration of adjuvant chemotherapy in stage III colon cancer patients.

Changes in IL-16 Expression in the Ovary during Aging and Its Potential Consequences to Ovarian Pathology.

Aging in females is not only associated with the changes in hormonal status but is also responsible for dysregulation of immune functions in various organs including ovaries. The goal of this study was to determine whether the expression of interleukin 16 (IL-16), a proinflammatory and chemoattractant cytokine, changes during ovarian aging, to determine factors involved in such changes in IL-16 expression, and to examine if changes in IL-16 expression during aging predisposes the ovary to pathologies. Ovarian tissues from premenopausal women (30-50 years old), women at early menopause (55-59 years old), and late menopause (60-85 years old) were used. In addition, tumor tissues from patients with ovarian high-grade serous carcinoma at early stage (n = 5) were also used as reference tissue for comparing the expression of several selected markers in aging ovaries. The expression of IL-16, frequency of macrophages (a source of IL-16) and expression of microRNA (miR) 125a-5p (a regulator of IL-16 gene) were performed by immunohistochemistry, immunoblotting, and gene expression assays. In addition, we examined changes in nuclear expression of IL-16 expression with regards to exposure to follicle-stimulating hormone (FSH) by in vitro cell culture assays with human ovarian cancer cells. The frequencies of IL-16 expressing cells were significantly higher in ovarian stroma in women at early and late menopause as compared with premenopausal women (P < 0.0001). Similar patterns were also observed for macrophages. Expression of miR-125a-5p decreased significantly (P < 0.001) with the increase in IL-16 expression during aging. Furthermore, expression of nuclear IL-16 increased remarkably upon exposure to FSH. Consequently, ovarian aging is associated with increased expression of IL-16 including its nuclear fraction. Therefore, persistent high levels of FSH in postmenopausal women may be a factor for enhanced expression of IL-16. Effects of increased nuclear fraction of IL-16 need to be examined.

Pragmatic Clinical Trial to Improve Patient Experience Among Adults During Transitions from Hospital to Home: the PArTNER study.

INTRODUCTION: Minority-serving hospitals (MSHs) need evidence-based strategies tailored to the populations they serve to improve patient-centered outcomes after hospitalization. METHODS: We conducted a pragmatic randomized clinical trial (RCT) from October 2014 to January 2017 at a MSH comparing the effectiveness of a stakeholder-supported Navigator intervention vs. Usual care on post-hospital patient experience, outcomes, and healthcare utilization. Community health workers and peer coaches delivered the intervention which included (1) in-hospital visits to assess barriers to health/healthcare and to develop a personalized Discharge Patient Education Tool (DPET); (2) a home visit to review the DPET; and (3) telephone-based peer coaching. The co-primary outcomes were between-group comparisons of 30-day changes in Patient-Reported Outcomes Measurement Information System (PROMIS) measures of anxiety and informational support (minimum important difference is 2 to 5 units change); a p-value <0.025 was considered significant using intention-to-treat analysis. Secondary outcomes included death, ED visits, or readmissions and measures of emotional, social, and physical health at 30 and 60 days. RESULTS: We enrolled 1029 adults hospitalized with heart failure (28%), pneumonia (22%), MI (10%), COPD (11%), or sickle cell disease (29%). Over 80% were non-Hispanic Black. Overall, there were no significant between-group differences in the 30-day change in anxiety (adjusted difference: -1.6, 97.5% CI -3.3 to 0.1, p=0.03), informational support (adjusted difference: -0.01, 97.5% CI -2.0 to 1.9, p=0.99), or any secondary outcomes. Exploratory analyses suggested the Navigator intervention improved anxiety among participants with COPD, a primary care provider, a hospitalization in the past 12 months, or higher baseline anxiety; among participants without health insurance, the intervention improved informational support (all p-values <0.05). CONCLUSIONS: In this pragmatic RCT at a MSH, the Navigator intervention did not improve post-hospital anxiety, informational support, or other outcomes compared to Usual care. Benefits observed in participant subgroups should be confirmed in future studies. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02114515.

Incidence of malignant transformation in the oviductal fimbria in laying hens, a preclinical model of spontaneous ovarian cancer.

Ovarian high grade serous carcinoma (HGSC) is a lethal form of ovarian cancer (OVCA). In most cases it is detected at late stages as the symptoms are non-specific during early stages. Emerging information suggests that the oviductal fimbria is a site of origin of ovarian HGSC. Currently available tests cannot detect ovarian HGSC at early stage. The lack of a preclinical model with oviductal fimbria that develops spontaneous ovarian HGSC is a significant barrier to developing an early detection test for this disease. The goal of this study was to examine if the oviductal fimbria in hens is a site of origin of HGSC and whether it expresses several putative markers expressed in ovarian HGSC in patients. A total of 135 laying hens (4 years old) were selected from a flock using transvaginal ultrasound (TVUS) imaging, followed by euthanasia and gross examination for the presence of solid masses and ascites. Histological types of carcinomas were determined by hematoxylin and eosin staining. Expression of WT-1, mutant p53, CA-125, PAX2 and Ki67 in normal or malignant fimbriae or ovaries were examined using immunohistochemistry, immunoblotting and gene expression assays. This study detected tumors in oviductal fimbriae in hens and routine staining revealed ovarian HGSC-like microscopic features in these tumors. These tumors showed similarities to ovarian HGSC in patients in expressing several markers. Compared with normal fimbriae, intensities of expression of WT-1, mutant p53, CA-125, and Ki67 were significantly (P<0.05) higher in fimbrial tumors. In contrast, expression of PAX2 decreased gradually as the tumor progressed to late stages. The patterns of expression of these markers were similar to those in ovarian HGSC patients. Thus, tumors of the oviductal fimbria in hens may offer a preclinical model to study different aspects of spontaneous ovarian HGSC in women including its early detection.

Redefining the Risk of Surgery for Clinical Stage IIIA (N2) Non-Small Cell Lung Cancer: A Pooled Analysis of the STS GTSD and ESTS Registry.

BACKGROUND: Management of clinical stage IIIA-N2 (cIIIA-N2) non-small cell lung cancer (NSCLC) remains controversial. We evaluated treatment strategies and outcomes in cIIIA-N2 NSCLC patients who underwent pulmonary resection in The Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTSD) and the European Society of Thoracic Surgeons (ESTS) Registry. METHODS: The STS GTSD and ESTS Registry were queried for patients who underwent pulmonary resection for cIIIA-N2 NSCLC between 2012 and 2016. Demographic variables, treatment strategies, and outcome measures were collected and analyzed. Significance of differences was determined using the χ2 test for categorical variables and the Wilcoxon rank sum test for continuous variables. RESULTS: Pulmonary resection was performed in 4279 cIIIA-N2 NSCLC patients (2928 STS GTSD; 1351 ESTS). Induction therapy was administered to 49%. Lobectomy was performed in 67.1% and pneumonectomy in 13%. Lobectomy was associated with 19.2% major morbidity and 1.6% operative mortality, while pneumonectomy was associated with 34.1% and 5%, respectively. Induction therapy was associated with a higher rate of major morbidity or mortality than upfront surgery (23.2% vs 19.5%, p = 0.004), driven by pneumonectomy (40.7% vs 30.3%, p = 0.012) rather than lobectomy (20.3% vs 18.8%, p = 0.31). CONCLUSIONS: Pulmonary resection for cIIIA-N2 NSCLC is associated with low rates of operative morbidity and mortality, with lobectomy having lower morbidity and mortality than pneumonectomy. Induction therapy, particularly chemoradiotherapy, is associated with a higher rate of composite morbidity or mortality than upfront surgery in pneumonectomy patients but not lobectomy patients.

Sarcopenia after induction therapy is associated with reduced survival in patients undergoing esophagectomy for locally-advanced esophageal cancer.

BACKGROUND: The impact of sarcopenia on the outcome of esophageal cancer patients remains unknown in North American populations. The current study aims to investigate if sarcopenia at the time of esophagectomy for locally-advanced esophageal cancer (LAEC) is associated with survival. METHODS: Patients who underwent induction therapy followed by esophagectomy for LAEC between 2010-2018 at a single institution were identified. Exclusion criteria included follow-up less than 90 days and distant metastatic disease at the time of surgery. Demographic, treatment, and outcome data were retrospectively collected. Computed tomography (CT) scans following induction therapy were analyzed to calculate skeletal muscle index (SMI). Overall survival (OS) and disease-free survival (DFS) were examined using Kaplan-Meier and Cox Proportional Hazard regression analysis. RESULTS: Overall, 52 patients met inclusion criteria with a median BMI of 25 (IQR, 22.4-29.1) kg/m2 and age of 65 (IQR, 57-70) years. Sarcopenia was present in 75% (39/52) of patients at the time of surgery. Sarcopenic patients had a lower median BMI and higher median age when compared to non-sarcopenic patients. There was no difference in gender, race, stage, operative technique, post-operative complications, or hospital length of stay between sarcopenic and non-sarcopenic patients. With a median follow-up of 24.9 months, patients with sarcopenia at the time of esophagectomy had worse OS [median 24.3 (IQR, 9.9-34.5) vs. 50.9 (IQR, 25.6-50.9) months, P=0.0292] and DFS [median 11.7 (IQR, 6.4-25.8) vs. 29.4 (IQR, 12.8-26.7) months, P=0.0387] compared to non-sarcopenic patients. CONCLUSIONS: Sarcopenia is associated with reduced overall and DFS in patients undergoing esophagectomy for LAEC.

Effect of the Paris system for reporting urinary cytology with histologic follow-up.

BACKGROUND: The Paris system (TPS) for Reporting Urinary Cytology provides a standardized reporting system whose main focus is the diagnosis of high-grade urothelial carcinoma (HGUC). We conducted a study to see the impact of The Paris System on our cytologic diagnoses with associated histology. MATERIALS AND METHODS: We reviewed our pathology database regarding urinary specimens in the year before implementation of The Paris System and the year after. We gathered the data regarding cytologic diagnosis and concurrent/subsequent histology. RESULTS: Over a 1-year period from 2016-2017, 486 urine cytology specimens were identified before implementation of The Paris System and diagnosed as follows: 83% benign/negative, 10% atypical, 2% suspicious, 5% HGUC, 0.2% low grade urothelial neoplasm (LGUN), and 0.2% unsatisfactory. Over a next 1-year period from 2017 to 2018, 602 specimens used TPS and diagnosed as follows: 85% negative for HGUC, 6% atypical, 3% suspicious, 4% HGUC, 0.17% LGUN, and 2% unsatisfactory. Although, not listed as a standardized category in The Paris System, our institution used "Negative for high-grade, cannot rule out low-grade urothelial neoplasm (NHL)" as a subcategory of Negative for HGUC. 4% of the cases fell into this category. Focusing on the Atypical category before TPS, histology was available in 15/49 (31%) cases. Of these, 40% had HGUC. Regarding the Atypical category after TPS, histology was available in 21/36 (58%) cases. Of these, 52% were HGUC. For the NHL category, concurrent histology was available in 13/26 (50%) cases. Of these, 67% were low grade urothelial neoplasms. CONCLUSION: Our study showed that TPS lowered the rate of Atypical from 10% to 6%. After the implementation of TPS, Atypical corresponded to a higher rate of high-grade urothelial carcinoma. Also, the NHL subcategory had a high positive predictive value for diagnosing low grade urothelial neoplasms.