The Impact of Racial Disparities and the Social Determinants of Health on Esophageal and Gastric Cancer Outcomes.

Reducing long-standing inequities in gastric and esophageal cancers is a priority of patients, providers, and policy makers. Many social determinants of health influence risk factors for disease development, incidence, treatment, and outcomes of gastric and esophageal cancers.

Real-World Health Care Resource Use and Costs Among Patients With Chronic Lymphocytic Leukemia Treated With Venetoclax-Based and Bruton Tyrosine Kinase Inhibitor-Based Regimens in the Second-Line Setting.

PURPOSE: Real-world evidence comparing health care resource use (HRU) and costs between novel targeted therapies among patients with chronic lymphocytic leukemia (CLL) is lacking. We compared all-cause and CLL-specific HRU and costs between patients initiated on B-cell lymphoma 2 inhibitor (venetoclax)- or Bruton tyrosine kinase inhibitor (BTKi)-based regimens in the second-line (2L) setting. METHODS: This is a retrospective observational study using Optum Clinformatics Data Mart of adult patients with CLL/small lymphocytic lymphoma who received 2L venetoclax- or BTKi-based regimens (January 2018-December 2021) for the first time and had ≥one CLL diagnostic claim after 2L initiation and ≥two claims for venetoclax or BTKi. Baseline characteristics were balanced using stabilized inverse probability of treatment weights. Mean monthly cost difference (MMCD) between cohorts for all-cause and CLL-specific per patient per month (PPPM) costs was estimated. Rates of PPPM-HRU were compared between cohorts using rate ratios (RRs). RESULTS: Of 280 patients, median age 75.5 years, 64.6% and 35.4% received BTKi- versus venetoclax-based regimens, respectively. Most BTKi-treated patients received monotherapy (88.4%), whereas 62.3% of venetoclax-treated patients received combination therapy with anti-CD20 agents. The median duration of 2L therapy was 11.6 and 11.0 months for BTKi versus venetoclax cohorts, respectively. All-cause total costs were lower for venetoclax versus BTKi (MMCD [SE], $-2,497.64 [$1,006.77] in US dollars (USD); P = .01), driven by lower medication costs offsetting medical costs; trends were similar for CLL-specific estimates. Outpatient HRU was higher for venetoclax versus BTKi (RR all-cause: 1.22 versus CLL-specific: 1.64). CONCLUSION: Venetoclax was associated with total monthly cost savings versus BTKis, illustrating the economic value of time-limited venetoclax-based regimens in the 2L setting.

The Ability of Self-Report Methods to Accurately Diagnose Attention Deficit Hyperactivity Disorder: A Systematic Review.

OBJECTIVE: To identify and analyze all studies validating rating scales or interview-based screeners commonly used to evaluate ADHD in adults. METHOD: A systematic literature search identified all studies providing diagnostic accuracy statistics, including sensitivity and specificity, supplemented by relevant articles or test manuals referenced in reviewed manuscripts. RESULTS: Only 20 published studies or manuals provided data regarding sensitivity and specificity when tasked with differentiating those with and without ADHD. While all screening measures have excellent ability to correctly classify non-ADHD individuals (with negative predictive values exceeding 96%), false positive rates were high. At best, positive predictive values in clinical samples reached 61%, but most fell below 20%. CONCLUSION: Clinicians cannot rely on scales alone to diagnose ADHD and must undertake more rigorous evaluation of clients who screen positive. Furthermore, relevant classification statistics must be included in publications to help clinicians make statistically defensible decisions. Otherwise, clinicians risk inappropriately diagnosing ADHD.

Short-Term Outcomes of COVID-19 Pandemic on Non-Small Cell Lung Cancer Screening and Management.

Background To assess the impact of coronavirus disease 2019 (COVID-19) pandemic on non-small cell lung cancer (NSCLC) screening, staging, and management in a single health care system. Materials and Methods From November 2015 to December 2020, a total of 1,547 NSCLC cases was reported at our institution including 1,329 cases pre-COVID-19 and 218 cases during COVID-19. Pre-COVID-19 was defined as November 2015 to February 2020, while during COVID-19 was March 2020 to December 2020. Data were collected from tumor registry and medical record review. Patients with mesothelioma, lymphoma, small cell, or mixed small cell cancer were excluded from the study. Results Both pre-COVID-19 and during COVID-19 cohorts had similar comorbidities including age (70 vs. 71 years), current smokers (35 vs. 32%), and chronic obstructive lung disease (32 vs. 28%). The number of low-dose computed tomography lung cancer screening scans decreased by 25% during COVID-19 compared with pre-COVID-19 era. There were more cases of stage 1A NSCLC pre-COVID-19 (31 vs. 25%) and more stage 4 cancer during COVID-19 (42 vs. 33%); p = 0.01. The proportion of patients treated with radiotherapy was similar between pre-COVID-19 and during COVID-19 (49 vs. 50%), but fewer patients underwent surgery during COVID-19 (17 vs. 27%; p = 0.004). The median time to radiotherapy (67 days) and surgery (29 days) was similar between the groups. The unadjusted overall 6-month mortality after lung cancer diagnoses was higher during COVID-19 compared with pre-COVID-19 (28 vs. 22%; p = 0.04). Conclusion The COVID-19 pandemic resulted in delayed lung cancer screening scans, and more patients had diagnosis of advanced NSCLC; however, short-term mortality was unchanged.

Sex-specific splicing of Z- and W-borne nr5a1 alleles suggests sex determination is controlled by chromosome conformation.

Pogona vitticeps has female heterogamety (ZZ/ZW), but the master sex-determining gene is unknown, as it is for all reptiles. We show that nr5a1 (Nuclear Receptor Subfamily 5 Group A Member 1), a gene that is essential in mammalian sex determination, has alleles on the Z and W chromosomes (Z-nr5a1 and W-nr5a1), which are both expressed and can recombine. Three transcript isoforms of Z-nr5a1 were detected in gonads of adult ZZ males, two of which encode a functional protein. However, ZW females produced 16 isoforms, most of which contained premature stop codons. The array of transcripts produced by the W-borne allele (W-nr5a1) is likely to produce truncated polypeptides that contain a structurally normal DNA-binding domain and could act as a competitive inhibitor to the full-length intact protein. We hypothesize that an altered configuration of the W chromosome affects the conformation of the primary transcript generating inhibitory W-borne isoforms that suppress testis determination. Under this hypothesis, the genetic sex determination (GSD) system of P. vitticeps is a W-borne dominant female-determining gene that may be controlled epigenetically.

The Art and Science of Mentorship in Cardiothoracic Surgery: A Systematic Review of the Literature.

BACKGROUND: As academic cardiothoracic surgeons focus on producing a new generation of successful surgeon leaders, mentorship has emerged as one of the most important variables influencing professional and personal success and satisfaction. This review explores the literature to determine the benefits, qualities, and features of the mentor relationship. METHODS: A comprehensive review was performed in February 2020 of Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and the SCOPUS Database using "'mentor"' as a primary search term. The titles and abstracts of these publications were then reviewed by 2 of the authors to identify relevant sources addressing topics related to mentorship in cardiothoracic surgery and also to identify 4 specific areas of focus: (1) the value of mentorship, (2) the skills needed to be an effective mentor, (3) effective approaches for identifying and receiving mentorship, and (4) the unique considerations associated with mentorship for traditionally underrepresented populations in surgery. RESULTS: Of 16,469 articles reviewed, 167 relevant manuscripts were identified, and 62 were included. CONCLUSIONS: There is undeniable value in mentorship when navigating a career in cardiothoracic surgery. By sharing the most significant features and skills of both ideal mentors and mentees, this review hoped to provide a framework to improve the quality of mentorship from both sides.

Application of the Target Lipid Model to Assess Toxicity of Heterocyclic Aromatic Compounds to Aquatic Organisms.

Heterocyclic aromatic compounds can be found in crude oil and coal and often co-exist in environmental samples with their homocyclic aromatic counterparts. The target lipid model (TLM) is a modeling framework that relates aquatic toxicity to the octanol-water partition coefficient (KOW ) that has been calibrated and validated for hydrocarbons. A systematic analysis of the applicability of the TLM to heterocyclic aromatic compounds has not been performed. The objective of the present study was to compile reliable toxicity data for heterocycles and determine whether observed toxicity could be successfully described by the TLM. Results indicated that the TLM could be applied to this compound class by adopting an empirically derived coefficient that accounts for partitioning between water and lipid. This coefficient was larger than previously reported for aromatic hydrocarbons, indicating that these heterocyclic compounds exhibit higher affinity to target lipid and toxicity. A mechanistic evaluation confirmed that the hydrogen bonding accepting moieties of the heteroatoms helped explain differences in partitioning behavior. Given the TLM chemical class coefficient reported in the present study, heterocyclic aromatics can now be explicitly incorporated in TLM-based risk assessments of petroleum substances, other products, or environmental media containing these compounds. Environ Toxicol Chem 2021;40:3000-3009. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Limitations on Development of Polychlorinated Biphenyl Tissue Concentration Thresholds for Survival, Growth, and Reproduction in Fish.

Polychlorinated biphenyl exposure-response relationships for ecologically relevant endpoints in fish vary greatly whether based on lowest-effect thresholds (Berninger and Tillitt 2019) or all-response data (sensitivity analyses), which precludes use of a single fitted model per endpoint to predict risk or injury to mixed fish populations. PCB = polychlorinated biphenyl.

A data-driven framework for defining stages of oil weathering.

Oil weathering is often described subjectively after a spill. Adjectives like "moderate" and "severe" help define the extent of oil loss but fail to communicate quantitatively and reproducibly the degree of weathering. The use of subjective weathering terms often leads to misperceptions about persistence and toxicity of oil residues in the environment. The weathering of MC252 oil from the Deepwater Horizon spill started immediately after release during the 1500-m ascent to the sea surface and continued as it was transported on the surface and reached the shoreline. Weathering processes included evaporation, dissolution, photo-degradation, and biodegradation, among others. With extensive sample collection and detailed chemistry and source fingerprinting analyses, the Deepwater Horizon data provide a unique opportunity to evaluate weathering processes semi-quantitatively. An objective method of defining the degree of oil weathering is developed based on the detailed chemical results for over 700 MC252 oil samples from the environment.

Elevated CO2 regulates the Wnt signaling pathway in mammals, Drosophila melanogaster and Caenorhabditis elegans.

Carbon dioxide (CO2) is sensed by cells and can trigger signals to modify gene expression in different tissues leading to changes in organismal functions. Despite accumulating evidence that several pathways in various organisms are responsive to CO2 elevation (hypercapnia), it has yet to be elucidated how hypercapnia activates genes and signaling pathways, or whether they interact, are integrated, or are conserved across species. Here, we performed a large-scale transcriptomic study to explore the interaction/integration/conservation of hypercapnia-induced genomic responses in mammals (mice and humans) as well as invertebrates (Caenorhabditis elegans and Drosophila melanogaster). We found that hypercapnia activated genes that regulate Wnt signaling in mouse lungs and skeletal muscles in vivo and in several cell lines of different tissue origin. Hypercapnia-responsive Wnt pathway homologues were similarly observed in secondary analysis of available transcriptomic datasets of hypercapnia in a human bronchial cell line, flies and nematodes. Our data suggest the evolutionarily conserved role of high CO2 in regulating Wnt pathway genes.

Report from the Workforce on Diversity and Inclusion-The Society of Thoracic Surgeons Members' Bias Experiences.

Diversity and inclusion within The Society of Thoracic Surgeons is paramount to the growth and excellence of our specialty. As such, discussions about challenges that prevent our Society from achieving this goal are necessary. The Workforce on Diversity and Inclusion has been tasked with understanding our membership's comprehension and experience with bias, which is known to have a negative impact on those of female gender, minority race, sexual orientation status, and religious status. Bias contributes to the fact that we are far from gender parity within our Society's leadership and that we must make significant changes in order to achieve a diverse membership. Within this report, we discuss the literature regarding experience with gender- and racial/ethnic-directed implicit and explicit bias during surgical training and within the cardiothoracic surgical workforce. We also share survey results on members' experience with racial/ethnic-, gender-, and other minority demographic-directed bias.

STS, ESTS and JACS survey on surveillance practices after surgical resection of lung cancer.

OBJECTIVES: A 1995 survey of Society of Thoracic Surgeons (STS) members revealed wide variation in postresection lung cancer surveillance practices and pessimism regarding any survival benefit. We sought to compare contemporary practice patterns and attitudes among members of STS, European Society of Thoracic Surgeons (ESTS) and the Japanese Association for Chest Surgery (JACS). METHODS: A survey identical to the one conducted in 1995 was administered via mail or electronically. χ2 tests for associations were used to compare profiles of respondents and attitudes towards testing between groups. All the statistical tests were two-sided and P-values of 0.05 or less were considered statistically significant. RESULTS: A total of 2978 STS members (response rate 7.8%, n = 234), 1450 ESTS members (response rate 8.4%, n = 122) and 272 JACS (response rate 40.8%, n = 111) members were surveyed. Rate of guideline-recommended surveillance computed tomography was reported highest among ESTS respondents for stage I patients (22% ESTS, 3% STS and 6% JACS members, P < 0.001). However, both JACS and ESTS respondents reported higher rates of use of non-guidelines-recommended tests compared to STS respondents, which persisted on adjusted analyses. Regarding attitudes towards surveillance, more JACS and ESTS members either 'agree' or 'strongly agree' that routine testing for non-small-cell lung cancer recurrence results in potentially curative treatment (ESTS: 86%, STS: 70%, JACS: 90%, P < 0.001). Similarly, JACS and ESTS respondents believe that the current literature documents definitive survival benefits from routine follow-up testing (ESTS: 57%, STS: 30%, JACS: 62%, P < 0.001). CONCLUSIONS: The Japanese attitude towards surveillance is similar to that of ESTS members potentially highlighting significant differences between European and Asian surgeons compared to STS members. These differences clearly highlight the need for better prospective studies and joint recommendations to globally standardize practice.

What Constitutes Optimal Management of T1N0 Esophageal Adenocarcinoma?

PURPOSE AND DESIGN: Esophageal adenocarcinoma (EAC) develops as a consequence of gastroesophageal reflux disease and Barrett's esophagus (BE). While combination therapy with chemotherapy or concurrent chemoradiotherapy followed by esophagectomy improves survival in more advanced tumors, the optimal treatment strategy for early-stage EAC is undefined. Endoscopic eradication therapy, consisting of endoscopic resection and mucosal ablation, has revolutionized therapy for superficial (T1a) EAC in BE and allows for esophageal preservation in appropriate patients at low risk for lymph node metastasis (LNM). This review critically examines the literature regarding evaluation, treatment, and outcomes in patients with T1 EAC. METHODS: The literature was queried via the PubMed database to include articles published between 1990 and 2017. Search terms were generated from the key statements "Endoscopic eradication therapy results in equivalent overall survival when compared to esophagectomy for clinical T1aN0 EAC" and "Esophagectomy provides better overall survival than endoscopic eradication therapy for cT1b EAC". Abstracts were reviewed and included according to predefined selection and exclusion criteria, and were then assessed according to the GRADE system. RESULTS AND CONCLUSIONS: In patients with T1aN0 EAC, overall survival with endoscopic eradication therapy is equal to esophagectomy. Given the substantial risk of LNM in patients with submucosal (T1b) EAC, esophagectomy remains the standard of care for surgical candidates. In the case of inoperability or low-risk lesions, endoscopic resection may be considered adequate therapy. Chemotherapy and radiation can be offered as primary therapy for non-surgical candidates with lesions not amenable to endoscopic therapy, but does not have a clear role in the adjuvant setting after either endoscopic or surgical resection.

Defining Proficiency for The Society of Thoracic Surgeons Participants Performing Thoracoscopic Lobectomy.

BACKGROUND: Parameters defining attainment and maintenance of proficiency in thoracoscopic video-assisted thoracic surgery (VATS) lobectomy remain unknown. To address this knowledge gap, this study investigated the institutional performance curve for VATS lobectomy by using risk-adjusted cumulative sum (Cusum) analysis. METHODS: Using The Society of Thoracic Surgeons General Thoracic Surgery Database, the study investigators identified centers that had performed a total of 30 or more VATS lobectomies. Major morbidity, mortality, and blood transfusion were deemed primary outcomes, with expected incidence derived from risk-adjusted regression models. Acceptable and unacceptable failure rates for outcomes were set a priori according to clinical relevance and informed by regression model output. RESULTS: Between 2001 and 2016, 24,196 patients underwent VATS lobectomy at 159 centers with a median volume of 103 (range, 30 to 760). Overall rates of operative mortality, major morbidity, and transfusion were 1% (244 of 24,189), 17.1% (4,145 of 24,196), and 4% (975 of 24,196), respectively. Of the highest-volume centers (≥100 cases), 84% (65 of 77) and 82 % (63 of 77) (p = 0.48) were proficient by major morbidity standards by their 50th and 100th cases, respectively. Similarly, 92% (71 of 77) and 90% (69 of 77) (p = 0.41) of centers showed proficiency by transfusion standards by their 50th and 100th cases, respectively. Three performance patterns were observed: (1) initial and sustained proficiency, (2) crossing unacceptability thresholds with subsequent improved performance; and (3) crossing unacceptability thresholds without subsequent improved performance. CONCLUSIONS: VATS lobectomy outcomes have improved with lower mortality and transfusion rates. The majority of high-volume centers demonstrated proficiency after 50 cases; however, maintenance of proficiency is not ensured. Cusum provides a simple yet powerful tool that can trigger internal audits and performance improvement initiatives.

Disparity between recent graduates' and experienced surgeons' assessment of time to operative independence.

BACKGROUND: In cardiothoracic surgery, little data exist on the transition to operative independence. We aimed to compare current perceptions of operative autonomy of junior cardiothoracic surgeons and senior colleagues who oversee transitional years. METHODS: An anonymous online survey was sent to currently practicing North American board-certified/eligible cardiothoracic surgeons to assess reported time to operative independence and comfort with cardiothoracic operations. The χ2 test, Fisher exact test, and Mann-Whitney U test were used to compare junior surgeons' self-reported experience to the junior experience as reported by the midcareer and senior surgeons with whom they practiced. Logistic regression was performed to assess factors associated with operative independence. RESULTS: Responses from 436 completed surveys were analyzed (82 juniors and 354 midcareer/seniors). Two hundred fifty-four midcareer/senior surgeons reported on the experience of 531 junior partners. Juniors reported high immediate posttraining comfort with basic cardiac cases and moderate comfort with all other categories. Time to operative independence was significantly different between juniors' self-report and midcareer/senior reports of junior partners except for complex thoracic cases. In multivariable logistic regression analysis, senior, and not midcareer, surgeon status was independently associated with junior operative independence status for cardiac cases and for basic thoracic cases. CONCLUSIONS: Most junior surgeons perceived operative independence with basic thoracic, basic cardiac, and complex cardiac operations earlier in their surgical career than that reported by senior colleagues. Objective measures of operative independence may clarify this discrepancy. This study establishes a baseline by which to compare the effects of integrated 6-year programs on operative independence. The discrepant perceptions may have implications for how training programs prepare graduates for the transition to independent practice.

Complications After Esophagectomy Are Associated With Extremes of Body Mass Index.

BACKGROUND: Body mass index (BMI) is not routinely taken into consideration for risk stratification prior to esophagectomy. Extremes of BMI are associated with adverse surgical outcomes in a variety of surgical specialties. We assessed the relationship of BMI to outcomes after esophagectomy for cancer. METHODS: Patients in the Society of Thoracic Surgeons General Thoracic Surgery Database (2009 to 2016) who underwent elective esophagectomy for cancer were selected for analysis. Open and minimally invasive approaches were included. Complications were categorized based on the Esophagectomy Complications Consensus Group recommendations. Multivariable logistic regression was used to adjust for confounding variables. RESULTS: We evaluated 9,389 patients grouped by BMI: underweight (<18.5 kg/m2; 3%), normal (18.5 to 24.9 kg/m2; 32%), overweight (25 to 29.9 kg/m2; 36%), obese I (30 to 34.9 kg/m2; 19%), obese II (35 to 39.9 kg/m2; 7%), and obese III (≥40 kg/m2; 3%). Most patients underwent open Ivor Lewis (33%), open transhiatal (23%), or minimally invasive Ivor Lewis (22%) approaches. The operative mortality rate was 3.4%; the frequency of complications by category ranged from 4% to 28%. On multivariable analysis, overall differences were identified among BMI categories for 7 out of 9 complication types. Underweight and obese III categories were associated with increased risk. In contrast, overweight and obese I BMI were associated with decreased risk for most complication types. CONCLUSIONS: BMI is associated with postoperative complications after esophagectomy. Postoperative risk assessment and prehabilitation regimens should be adjusted accordingly when planning an esophagectomy for a patient with very low or very high BMI.

Novel Aberrations Uncovered in Barrett's Esophagus and Esophageal Adenocarcinoma Using Whole Transcriptome Sequencing.

Esophageal adenocarcinoma (EAC) has one of the fastest increases in incidence of any cancer, along with poor five-year survival rates. Barrett's esophagus (BE) is the main risk factor for EAC; however, the mechanisms driving EAC development remain poorly understood. Here, transcriptomic profiling was performed using RNA-sequencing (RNA-seq) on premalignant and malignant Barrett's tissues to better understand this disease. Machine-learning and network analysis methods were applied to discover novel driver genes for EAC development. Identified gene expression signatures for the distinction of EAC from BE were validated in separate datasets. An extensive analysis of the noncoding RNA (ncRNA) landscape was performed to determine the involvement of novel transcriptomic elements in Barrett's disease and EAC. Finally, transcriptomic mutational investigation of genes that are recurrently mutated in EAC was performed. Through these approaches, novel driver genes were discovered for EAC, which involved key cell cycle and DNA repair genes, such as BRCA1 and PRKDC. A novel 4-gene signature (CTSL, COL17A1, KLF4, and E2F3) was identified, externally validated, and shown to provide excellent distinction of EAC from BE. Furthermore, expression changes were observed in 685 long noncoding RNAs (lncRNA) and a systematic dysregulation of repeat elements across different stages of Barrett's disease, with wide-ranging downregulation of Alu elements in EAC. Mutational investigation revealed distinct pathways activated between EAC tissues with or without TP53 mutations compared with Barrett's disease. In summary, transcriptome sequencing revealed altered expression of numerous novel elements, processes, and networks in EAC and premalignant BE.Implications: This study identified opportunities to improve early detection and treatment of patients with BE and esophageal adenocarcinoma. Mol Cancer Res; 15(11); 1558-69. ©2017 AACR.

Changes in gene expression of neo-squamous mucosa after endoscopic treatment for dysplastic Barrett's esophagus and intramucosal adenocarcinoma.

BACKGROUND: Endoscopic therapy, including by radiofrequency ablation (RFA) or endoscopic mucosal resection (EMR), is first line treatment for Barrett's esophagus (BE) with high-grade dysplasia (HGD) or intramucosal cancer (IMC) and may be appropriate for some patients with low-grade dysplasia (LGD). OBJECTIVE: The purpose of this study was to investigate the molecular effects of endotherapy. METHODS: mRNA expression of 16 genes significantly associated with different BE stages was measured in paired pre-treatment BE tissues and post-treatment neo-squamous biopsies from 36 patients treated by RFA (19 patients, 3 IMC, 4 HGD, 12 LGD) or EMR (17 patients, 4 IMC, 13 HGD). EMR was performed prior to RFA in eight patients. Normal squamous esophageal tissues were from 20 control individuals. RESULTS: Endoscopic therapy resulted in significant change towards the normal squamous expression profile for all genes. The neo-squamous expression profile was significantly different to the normal control profile for 11 of 16 genes. CONCLUSION: Endotherapy results in marked changes in mRNA expression, with replacement of the disordered BE dysplasia or IMC profile with a more "normal" profile. The neo-squamous mucosa was significantly different to the normal control squamous mucosa for most genes. The significance of this finding is uncertain but it may support continued endoscopic surveillance after successful endotherapy.