The role of multiple mediation with contextual neighborhood measures in ovarian cancer survival.

BACKGROUND: Mediation by multiple agents can affect the relation between neighborhood deprivation and segregation indices and ovarian cancer survival. In this paper, we examine a variety of potential clinical mediators in the association between deprivation indices (DIs) and segregation indices (SIs) with all-cause survival among women with ovarian cancer in the African American Cancer Epidemiology Study (AACES). METHODS: We use novel Bayesian multiple mediation structural models to assess the joint role of mediators (stage at diagnosis, histology, diagnostic delay) combined with the DIs and SIs (Yost, ADI, Kolak's URB, ICE-income) and a set of confounders with survival. The confounder set is selected in a preliminary step, and each DI or SI is included in separate model fits. RESULTS: When multiple mediators are included, the total impact of DIs and SIs on survival is much reduced. Unlike the single mediator examples previously reported, the Yost, ADI and ICE-income indices do not display significant direct effects. This suggests that when important clinical mediators are included, the impact of neighborhood SES indices is significantly attenuated. It is also clear that certain behavioral and demographic measures such as physical activity, smoking, or adjusted family income do not have a significant role in survival when mediated by clinical factors. CONCLUSION: Multiple mediation via clinical and diagnostic-related measures reduces the contextual effects of neighborhood measures on ovarian cancer survival. The robust association of the Kolak URB index on survival may be due to its relevance to access to care, unlike SES-based indices whose impact was significantly reduced when important clinical mediators were included.

Single Cell Expression Analysis of Ductal Carcinoma in Situ Identifies Complex Genotypic-Phenotypic Relationships Altering Epithelial Composition.

To identify mechanisms underlying the growth of ductal carcinoma in situ (DCIS) and properties that lead to progression to invasive cancer, we performed single-cell RNA-sequencing (scRNA-seq) on DCIS lesions and matched synchronous normal breast tissue. Using inferred copy number variations (CNV), we identified neoplastic epithelial cells from the clinical specimens which contained a mixture of DCIS and normal ducts. Phylogenetic analysis based on the CNVs demonstrated intratumoral clonal heterogeneity was associated with significant gene expression differences. We also classified epithelial cells into mammary cell states and found that individual genetic clones contained a mixture of cell states suggesting an ongoing pattern of differentiation after neoplastic transformation. Cell state proportions were significantly different based on estrogen receptor (ER) expression with ER-DCIS more closely resembling the distribution in the normal breast, particularly with respect to cells with basal characteristics. Using deconvolution from bulk RNA-seq in archival DCIS specimens, we show that specific alterations in cell state proportions are associated with progression to invasive cancer. Loss of an intact basement membrane (BM) is the functional definition of invasive breast cancer (IBC) and scRNA-seq data demonstrated that ongoing transcription of key BM genes occurs in specific subsets of epithelial cell states. Examining BM in archival microinvasive breast cancers and an in vitro model of invasion, we found that passive loss of BM gene expression due to cell state proportion alterations is associated with loss of the structural integrity of the duct leading to an invasive phenotype. Our analyses provide detailed insight into DCIS biology. SIGNIFICANCE: Single cell analysis reveals that preinvasive breast cancer is comprised of multiple genetic clones and there is substantial phenotypic diversity both within and between these clones. Ductal carcinoma in situ (DCIS) of the breast is a non-invasive condition commonly identified through mammographic screening. A primary diagnosis of DCIS carries little mortality risk on its own, but its presence is a risk factor for subsequent clonally related invasive breast cancer (IBC) (1-5).

Elevated preoperative lower esophageal sphincter pressure predicts improved clinical outcomes after per oral endoscopic myotomy (POEM).

BACKGROUND: Although per oral endoscopic myotomy (POEM) has shown to be beneficial for the treatment of achalasia, it can be difficult to predict who will have a robust and long-lasting response. Historically, it has been shown that higher lower esophageal sphincter pressures have been associated with poorer responses to alternative endoscopic therapies such as Botox therapy and pneumatic dilation. This study was designed to evaluate if modern preoperative manometric data could similarly predict response to therapy after POEM. METHODS: This was a retrospective study of 237 patients who underwent POEM at a single institution over a period of 13 years (2011-2023) and who had a high-resolution manometry performed preoperatively and an Eckardt symptom score performed both preoperative and postoperatively. The achalasia type and integrated relaxation pressures (IRP) were tested for potential correlation with the need for any further achalasia interventions postoperatively as well as the degree of Eckardt score reduction using a linear regression model. RESULTS: The Achalasia type on preoperative manometry was not predictive for further interventions or degree of Eckardt score reduction (p = 0.76 and 0.43, respectively). A higher IRP was not predictive of the need for further interventions, however, it was predictive of a greater reduction in postoperative Eckardt scores (p = 0.03) as shown by the non-zero regression slope. CONCLUSION: In this study, achalasia type was not a predictive factor in the need for further interventions or the degree of symptom relief. Although IRP was not predictive of the need for further interventions, a higher IRP did predict better symptomatic relief postoperatively. This result is opposite that of other endoscopic treatment modalities (Botox and pneumatic dilation). Therefore, patients with higher IRP on preoperative high-resolution manometry would likely benefit from POEM which provides significant symptomatic relief postoperatively.

Analysis of ductal carcinoma in situ by self-reported race reveals molecular differences related to outcome.

BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive breast cancer (IBC). Studies have indicated differences in DCIS outcome based on race or ethnicity, but molecular differences have not been investigated. METHODS: We examined the molecular profile of DCIS by self-reported race (SRR) and outcome groups in Black (n = 99) and White (n = 191) women in a large DCIS case-control cohort study with longitudinal follow up. RESULTS: Gene expression and pathway analyses suggested that different genes and pathways are involved in diagnosis and ipsilateral breast outcome (DCIS or IBC) after DCIS treatment in White versus Black women. We identified differences in ER and HER2 expression, tumor microenvironment composition, and copy number variations by SRR and outcome groups. CONCLUSIONS: Our results suggest that different molecular mechanisms drive initiation and subsequent ipsilateral breast events in Black versus White women.

Does practice make perfect? Studying the relationship between surgeon experience and patient outcomes for paraesophageal hernia repairs.

BACKGROUND: It has been reported that higher surgeon experience leads to better patient outcomes. In this study, we look at surgeon experience and its association with postoperative outcomes and variation among the practice of surgeons performing paraesophageal hernia repairs (PEH). METHOD: This was a retrospective study of 1155 patients who underwent PEH repair at a single institution (2010-2023). Surgeon experience was defined as the number of surgeries performed per surgeon and was split using the median surgeries (n = 100), with surgeons performing at or above the median categorized as high-experience and below the median as low-experience surgeons. A multivariable logistic regression model was used to test correlation between surgeon experience and variables, including demographics and intra- and post-operative outcomes. RESULTS: High-experience surgeons performed more elective cases (93.4% vs 85.5%), but low-experience surgeons operated more on emergent (2.7% vs 0.9%), semi-elective (2.3% vs 1.4%), and urgent cases (9.5% vs 4.3%). Low-experience surgeons operated more on patients who were older (67.5 vs 63.2 years, p < 0.001) and had an increased risk of CVD (72.9% vs 61.5%, p < 0.001). Intraoperative OR time was considerably less for high-experience surgeons (115.8 vs 172.9 min, p < 0.001). Low-experience surgeons had increased risk of intra-operative complications (4.5% vs 1.8%, p = 0.021) and post-op pneumonia within 30 days (1.8% vs 0.3%). However, long-term outcomes such as hernia recurrence (OR: 1.10, CI: 0.78-1.54) and redo-operations for hiatal hernia (OR: 1.10, CI: 0.65-1.75) were similar for both groups. CONCLUSION: High-experience surgeons perform more complex revisional surgeries in less time with fewer complications. Low-experience surgeons operated more on patients with higher comorbidities but had significantly higher OR times. Long-term results of recurrence and redo-operations were comparable. These variations suggest that high-experience surgeons are more efficient while operating on more complex cases. These findings have pivotal implications to facilitate mentorship and education among less-experienced surgeons.

Initial experience and outcomes of per oral pyloromyotomy for the treatment of refractory gastroparesis.

BACKGROUND: Gastroparesis can be a debilitating disease process for which durable treatment options are lacking. While dietary changes and pharmacotherapy have some efficacy, symptoms frequently recur and some patients progress to needing supplemental enteral feeding access. Per oral pyloromyotomy (POP) has been shown to be a durable minimally invasive treatment option for refractory gastroparesis with a low side effect profile, and therefore has been performed at this institution for the past 6 years. METHODS: This was a retrospective case series of all patients who underwent a POP at a single institution over a 6-year period (2018-2023). Patient demographics, preoperative symptomatology and subsequent workup, postoperative complications, and symptom recurrence were collected and analyzed. RESULTS: There were 56 patients included in the study. There was a 1.8:1 female:male ratio. The average patient age was 56 years old (range 23-85). The average duration of symptoms was 1-3 years. Thirty-eight percent of patients had undergone previous endoscopic therapy for gastroparesis (pyloric botox injection or pyloric dilation) and 16% of patients underwent multiple endoscopic therapies. Twenty-nine percent of patients were on a medication for gastroparesis. Past surgery was the most common gastroparesis etiology for POP (50% of patients). Diabetes (23%) and idiopathic (19%) were the other most common gastroparesis etiologies for POP. Nausea was the most common symptom at first follow-up (30%) but these patients continued to improve with 14% of patients continuing to endorse nausea at 6 months. Twenty-seven percent of patients developed symptom recurrence. Forty percent of patients with symptom recurrence underwent a repeat endoscopic or surgical therapy. CONCLUSIONS: In this present study, POP leads to durable results in approximately 75% of patients with minimal complications. Furthermore, the majority of patients who do develop symptom recurrence do not require additional gastroparesis interventions.

Evolutionary Measures Show that Recurrence of DCIS is Distinct from Progression to Breast Cancer.

Progression from pre-cancers like ductal carcinoma in situ (DCIS) to invasive disease (cancer) is driven by somatic evolution and is altered by clinical interventions. We hypothesized that genetic and/or phenotypic intra-tumor heterogeneity would predict clinical outcomes for DCIS since it serves as the substrate for natural selection among cells. We profiled two samples from two geographically distinct foci from each DCIS in both cross-sectional (N = 119) and longitudinal cohorts (N = 224), with whole exome sequencing, low-pass whole genome sequencing, and a panel of immunohistochemical markers. In the longitudinal cohorts, the only statistically significant predictors of time to non-invasive DCIS recurrence were the combination of treatment (lumpectomy only vs mastectomy or lumpectomy with radiation, HR = 12.13, p = 0.003, Wald test with FDR correction), ER status (HR = 0.16 for ER+ compared to ER-, p = 0.0045), and divergence in SNVs between the two samples (HR = 1.33 per 10% divergence, p = 0.018). SNV divergence also distinguished between pure DCIS and DCIS synchronous with invasive disease in the cross-sectional cohort. In contrast, the only statistically significant predictors of time to progression to invasive disease were the combination of the width of the surgical margin (HR = 0.67 per mm, p = 0.043) and the number of mutations that were detectable at high allele frequencies (HR = 1.30 per 10 SNVs, p = 0.02). These results imply that recurrence with DCIS is a clinical and biological process different from invasive progression.

Does preoperative symptom duration affect outcomes following per oral endoscopic myotomy (POEM)?

BACKGROUND: Per oral endoscopic myotomy (POEM) is a safe therapy for the treatment of achalasia. Long-term effects of untreated achalasia include worsening dysmotility and disruptions in esophageal anatomy, i.e., tortuosity and dilation. We hypothesize that long-standing achalasia prior to intervention will have worse outcomes following POEM than in patients with symptoms for shorter duration. METHODS: We retrospectively analyzed achalasia patients who underwent POEM at our institution from 2011 to 2023, categorizing them into symptom duration cohorts (< 1 year, 1-3 years, 4-10 years, > 10 years). Inclusion criteria comprised patients with documented achalasia diagnosis who received POEM treatment at our facility. Exclusion criteria encompassed individuals lacking data pertaining to achalasia diagnosis, the time frame before intervention, or those missing pre and postoperative Eckardt scores. POEM failure was defined as symptom recurrence, necessity for repeat intervention, or high postoperative Eckardt score. We compared demographic, preoperative, and postoperative outcomes across these cohorts, and employed multivariable logistic regression to explore the link between symptom duration and POEM response. RESULTS: During the study period, in our increased cohort 234 patients met inclusion criteria. 75 patients had symptoms for < 1 year, 78 patients had symptoms from 1 to 3 years, 47 patients had symptoms from 4 to 10 years, and 34 patients had symptoms > 10 years. Patient demographics such as age, sex, BMI, Charleson-Deyo-Comorbidity-Index, and diabetes did not differ amongst cohorts. High-resolution manometry data, including achalasia type, Median IRP, LES residual pressure, and Basal LES pressure did not differ between groups. Preoperative Eckardt scores ranged from 4 to 5 across groups (p 0.24). Patients endorsed an average of three total preoperative symptoms across groups (p 0.13). Patients with symptoms greater than 4 years had significantly more endoscopic interventions prior to POEM (37% vs, 68% p .001). There was no significant difference in post-procedure mean Eckardt scores between cohorts. All cohorts experienced the same number of post-POEM symptoms. Post-POEM manometric measurements remained consistent across cohorts. Similarly, there were no significant differences in terms of symptom recurrence, requirement for repeat interventions, or repeat POEM among the cohorts. Multivariable logistic regression analysis determined achalasia symptoms greater than a decade did not result in increased odds of having a higher postoperative Eckardt score, worse dysphagia, regurgitation, or weight loss. CONCLUSIONS: In this increased cohort, this data once again suggests that longer symptom duration is not associated with increased rates of POEM failure.

Evaluation of postoperative esophagram following peroral endoscopic myotomy (POEM).

INTRODUCTION: The routine use of post-operative esophogram has come under evaluation for multiple upper GI surgeries such as with bariatric surgery and gastric resections. A major complication following Per Oral Endoscopic Myotomy (POEM) is a leak from the myotomy site. A post-operative contrast esophogram is often utilized to evaluate the presence of a leak, however it is not a standardized care practice for all patients. Presently it is selectively performed depending on physician assessment intra-operatively. This project will evaluate the necessity of post-operative contrast esophogram following POEM. MATERIALS AND METHODS: We retrospectively reviewed 277 patients diagnosed with achalasia who underwent POEM by two surgeons from 2011 to 2022. 173 patients met the inclusion criteria. A post-operative esophogram was used for the evaluation of a leak. Post-operative esophagram were selectively performed on day 1 following surgery using a water-soluble material. Data was evaluated using Stata. RESULTS: There were 3 detected leaks in the group that underwent esophagrams compared to the non-esophagram group in the early post-operative period. The overall complication rate was 5.5% in the non-esophagram versus 7.9% in the esophagram group. Length of stay was 1.48 days in the non-UGI vs 1.76 days in the esophagram group. Readmission rate was 10.9% in non-esophagram versus 8.7% in esophagram group. CONCLUSION: There was no statistically significant difference in outcomes in patients undergoing POEM who received post-operative esophagram verses patients who did not receive post-operative esophagram. The routine use of a contrast esophogram to detect a leak following POEM may not be justified. This study suggests that esophagrams should be performed depending on the clinical signs/symptoms post-operatively that would warrant imaging and intervention.

Extracellular Microenvironment Alterations in Ductal Carcinoma In Situ and Invasive Breast Cancer Pathologies by Multiplexed Spatial Proteomics.

Ductal carcinoma in situ (DCIS) is a heterogeneous breast disease that remains challenging to treat due to its unpredictable progression to invasive breast cancer (IBC). Contemporary literature has become increasingly focused on extracellular matrix (ECM) alterations with breast cancer progression. However, the spatial regulation of the ECM proteome in DCIS has yet to be investigated in relation to IBC. We hypothesized that DCIS and IBC present distinct ECM proteomes that could discriminate between these pathologies. Tissue sections of pure DCIS, mixed DCIS-IBC, or pure IBC (n = 22) with detailed pathological annotations were investigated by multiplexed spatial proteomics. Across tissues, 1,005 ECM peptides were detected in pathologically annotated regions and their surrounding extracellular microenvironments. A comparison of DCIS to IBC pathologies demonstrated 43 significantly altered ECM peptides. Notably, eight fibrillar collagen peptides could distinguish with high specificity and sensitivity between DCIS and IBC. Lesion-targeted proteomic imaging revealed heterogeneity of the ECM proteome surrounding individual DCIS lesions. Multiplexed spatial proteomics reported an invasive cancer field effect, in which DCIS lesions in closer proximity to IBC shared a more similar ECM profile to IBC than distal counterparts. Defining the ECM proteomic microenvironment provides novel molecular insights relating to DCIS and IBC.

Molecular Subtypes of High-Grade Serous Ovarian Cancer across Racial Groups and Gene Expression Platforms.

BACKGROUND: High-grade serous carcinoma (HGSC) gene expression subtypes are associated with differential survival. We characterized HGSC gene expression in Black individuals and considered whether gene expression differences by self-identified race may contribute to poorer HGSC survival among Black versus White individuals. METHODS: We included newly generated RNA sequencing data from Black and White individuals and array-based genotyping data from four existing studies of White and Japanese individuals. We used K-means clustering, a method with no predefined number of clusters or dataset-specific features, to assign subtypes. Cluster- and dataset-specific gene expression patterns were summarized by moderated t-scores. We compared cluster-specific gene expression patterns across datasets by calculating the correlation between the summarized vectors of moderated t-scores. After mapping to The Cancer Genome Atlas-derived HGSC subtypes, we used Cox proportional hazards models to estimate subtype-specific survival by dataset. RESULTS: Cluster-specific gene expression was similar across gene expression platforms and racial groups. Comparing the Black population with the White and Japanese populations, the immunoreactive subtype was more common (39% vs. 23%-28%) and the differentiated subtype was less common (7% vs. 22%-31%). Patterns of subtype-specific survival were similar between the Black and White populations with RNA sequencing data; compared with mesenchymal cases, the risk of death was similar for proliferative and differentiated cases and suggestively lower for immunoreactive cases [Black population HR = 0.79 (0.55, 1.13); White population HR = 0.86 (0.62, 1.19)]. CONCLUSIONS: Although the prevalence of HGSC subtypes varied by race, subtype-specific survival was similar. IMPACT: HGSC subtypes can be consistently assigned across platforms and self-identified racial groups.

Classification performance bias between training and test sets in a limited mammography dataset.

OBJECTIVES: To assess the performance bias caused by sampling data into training and test sets in a mammography radiomics study. METHODS: Mammograms from 700 women were used to study upstaging of ductal carcinoma in situ. The dataset was repeatedly shuffled and split into training (n = 400) and test cases (n = 300) forty times. For each split, cross-validation was used for training, followed by an assessment of the test set. Logistic regression with regularization and support vector machine were used as the machine learning classifiers. For each split and classifier type, multiple models were created based on radiomics and/or clinical features. RESULTS: Area under the curve (AUC) performances varied considerably across the different data splits (e.g., radiomics regression model: train 0.58-0.70, test 0.59-0.73). Performances for regression models showed a tradeoff where better training led to worse testing and vice versa. Cross-validation over all cases reduced this variability, but required samples of 500+ cases to yield representative estimates of performance. CONCLUSIONS: In medical imaging, clinical datasets are often limited to relatively small size. Models built from different training sets may not be representative of the whole dataset. Depending on the selected data split and model, performance bias could lead to inappropriate conclusions that might influence the clinical significance of the findings. ADVANCES IN KNOWLEDGE: Performance bias can result from model testing when using limited datasets. Optimal strategies for test set selection should be developed to ensure study conclusions are appropriate.

Development of a Competency Framework Defining Effective Surgical Educators.

OBJECTIVE: The objective of this study is to develop a practical framework of competencies and behaviors which define an effective surgical educator. DESIGN: A modified Delphi approach was used. A literature review and series of discussions with surgical education experts led to creation of a survey instrument which was sent to surgical faculty and trainees from a single academic institution. The results from this initial survey informed the creation of the subsequent survey instrument which was also sent to surgical faculty and trainees. Focus groups with surgical faculty and residents were conducted separately, transcribed, deidentified, and then evaluated for recurring themes. A competency framework was developed. SETTING: The surveys were administered and focus groups were conducted at the University Hospitals Cleveland Medical Center, a tertiary care academic institution. PARTICIPANTS: Residents, fellows, and faculty surgeons from the fields of general surgery, plastic surgery, vascular surgery, orthopedic surgery, otolaryngology, neurosurgery, and urology. RESULTS: There were 115 responses (31.3%) from 367 faculty surgeons, residents, and fellows invited to complete the initial survey examining 50 competencies. Eighteen competencies received a mean Likert score of at least 4 by both faculty and residents and were included in the subsequent survey instrument which was completed by 72 participants (19.6%). Focus groups were held separately with 6 faculty surgeons and 6 residents. Analysis of the survey results and focus group discussions identified several themes which informed the development of a competency framework consisting of 5 overarching competencies as well as 16 specific behaviors. CONCLUSIONS: A practical framework was developed consisting of 5 competencies and 16 behaviors which define an effective surgical educator. The 5 competencies are: 1) fosters psychological safety, 2) displays exemplary medical knowledge and patient care, 3) diagnoses the learner and adjusts teaching, 4) communicates thought process to trainee, and 5) displays learner-centeredness. Based on the competency framework, residency leadership may specifically tailor faculty development initiatives to improve surgical education programming.

Molecular subtypes of high-grade serous ovarian cancer across racial groups and gene expression platforms.

Introduction: High-grade serous carcinoma (HGSC) gene expression subtypes are associated with differential survival. We characterized HGSC gene expression in Black individuals and considered whether gene expression differences by race may contribute to poorer HGSC survival among Black versus non-Hispanic White individuals. Methods: We included newly generated RNA-Seq data from Black and White individuals, and array-based genotyping data from four existing studies of White and Japanese individuals. We assigned subtypes using K-means clustering. Cluster- and dataset-specific gene expression patterns were summarized by moderated t-scores. We compared cluster-specific gene expression patterns across datasets by calculating the correlation between the summarized vectors of moderated t-scores. Following mapping to The Cancer Genome Atlas (TCGA)-derived HGSC subtypes, we used Cox proportional hazards models to estimate subtype-specific survival by dataset. Results: Cluster-specific gene expression was similar across gene expression platforms. Comparing the Black study population to the White and Japanese study populations, the immunoreactive subtype was more common (39% versus 23%-28%) and the differentiated subtype less common (7% versus 22%-31%). Patterns of subtype-specific survival were similar between the Black and White populations with RNA-Seq data; compared to mesenchymal cases, the risk of death was similar for proliferative and differentiated cases and suggestively lower for immunoreactive cases (Black population HR=0.79 [0.55, 1.13], White population HR=0.86 [0.62, 1.19]). Conclusions: A single, platform-agnostic pipeline can be used to assign HGSC gene expression subtypes. While the observed prevalence of HGSC subtypes varied by race, subtype-specific survival was similar.

Growth Dynamics of Ductal Carcinoma in Situ Recapitulate Normal Breast Development.

Ductal carcinoma in situ (DCIS) and invasive breast cancer share many morphologic, proteomic, and genomic alterations. Yet in contrast to invasive cancer, many DCIS tumors do not progress and may remain indolent over decades. To better understand the heterogenous nature of this disease, we reconstructed the growth dynamics of 18 DCIS tumors based on the geo-spatial distribution of their somatic mutations. The somatic mutation topographies revealed that DCIS is multiclonal and consists of spatially discontinuous subclonal lesions. Here we show that this pattern of spread is consistent with a new 'Comet' model of DCIS tumorigenesis, whereby multiple subclones arise early and nucleate the buds of the growing tumor. The discontinuous, multiclonal growth of the Comet model is analogous to the branching morphogenesis of normal breast development that governs the rapid expansion of the mammary epithelium during puberty. The branching morphogenesis-like dynamics of the proposed Comet model diverges from the canonical model of clonal evolution, and better explains observed genomic spatial data. Importantly, the Comet model allows for the clinically relevant scenario of extensive DCIS spread, without being subjected to the selective pressures of subclone competition that promote the emergence of increasingly invasive phenotypes. As such, the normal cell movement inferred during DCIS growth provides a new explanation for the limited risk of progression in DCIS and adds biologic rationale for ongoing clinical efforts to reduce DCIS overtreatment.

The Association between Mediated Deprivation and Ovarian Cancer Survival among African American Women.

BACKGROUND: Deprivation indices are often used to adjust for socio-economic disparities in health studies. Their role has been partially evaluated for certain population-level cancer outcomes, but examination of their role in ovarian cancer is limited. In this study, we evaluated a range of well-recognized deprivation indices in relation to cancer survival in a cohort of self-identified Black women diagnosed with ovarian cancer. This study aimed to determine if clinical or diagnostic characteristics lie on a mediating pathway between socioeconomic status (SES) and deprivation and ovarian cancer survival in a minority population that experiences worse survival from ovarian cancer. METHODS: We used mediation analysis to look at the direct and indirect causal effects of deprivation indices with main mediators of the SEER stage at diagnosis and residual disease. The analysis employed Bayesian structural equation models with variable selection. We applied a joint Bayesian structural model for the mediator, including a Weibull mixed model for the vital outcome with deprivation as exposure. We selected modifiers via a Monte Carlo model selection procedure. RESULTS: The results suggest that high SES-related indices, such as Yost, Kolak urbanicity (URB), mobility (MOB) and SES dimensions, and concentrated disadvantage index (CDI), all have a significant impact on improved survival. In contrast, area deprivation index (ADI)/Singh, and area level poverty (POV) did not have a major impact. In some cases, the indirect effects have very wide credible intervals, so the total effect is not well estimated despite the estimation of the direct effect. CONCLUSIONS: First, it is clear that commonly used indices such as Yost, or CDI both significantly impact the survival experience of Black women diagnosed with epithelial ovarian cancer. In addition, the Kolak dimension indices (URB, MOB, mixed immigrant: MICA and SES) also demonstrate a significant association, depending on the mediator. Mediation effects differ according to the mediator chosen.

Accuracy in Polyp Size Measurement Among Surgeons, Gastroenterologists, Trainees, and Experts: A Prospective Video-Based Study.

INTRODUCTION: Polyp size determination plays an important role in endoscopic decision making and follow-up determination. However, there is a lack of knowledge of endoscopist accuracy for polyp sizing and efficacy of available tools for size measurement. Our aim was to compare the accuracy of visual assessment, snare, forceps, and virtual scale endoscope (VSE) in estimating polyp size among a diverse group of endoscopists. METHODS: We conducted a prospective video-based study. One hundred twenty polyps measured and recorded along with all available measurement tools were randomized to visual assessment, snare, forceps, or VSE group. Eleven endoscopists conducted video-based measurement using the randomized measurement tool. Primary outcome was relative accuracy in polyp size measurement compared with caliper measurement immediately postresection. RESULTS: One thousand three hundred twenty measurements were performed. VSE had statistically significantly higher relative accuracy when compared to forceps (79.3 vs 71.3%; P < 0.0001). Forceps had statistically significantly higher relative accuracy when compared to visual assessment (71.3 vs 63.6%; P = 0.0036). There was no statistically significant difference when comparing visual assessment and snare-based measurements (63.6 vs 62.8%; P = 0.797). Overall, 21.5% of polyps >5 mm were misclassified as ≤5 mm and 17.3% of polyps ≥10 mm were misclassified as <10 mm. VSE had the lowest percentage of polyps >5 mm misclassified as ≤5 mm (2.6%), polyps ≤5 mm misclassified as >5 mm (5.1%), and polyps <10 mm misclassified as ≥10 mm (1.7%). DISCUSSION: Visual size estimation of polyps is inaccurate independently of training level, sex, and specialty. Size measurement accuracy can be improved using forceps and yields the highest relative accuracy when an adaptive scale technology is used.

Association of inflammation-related exposures and ovarian cancer survival in a multi-site cohort study of Black women.

BACKGROUND: An association was observed between an inflammation-related risk score (IRRS) and worse overall survival (OS) among a cohort of mostly White women with invasive epithelial ovarian cancer (EOC). Herein, we evaluated the association between the IRRS and OS among Black women with EOC, a population with higher frequencies of pro-inflammatory exposures and worse survival. METHODS: The analysis included 592 Black women diagnosed with EOC from the African American Cancer Epidemiology Study (AACES). Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of the IRRS and OS, adjusting for relevant covariates. Additional inflammation-related exposures, including the energy-adjusted Dietary Inflammatory Index (E-DIITM), were evaluated. RESULTS: A dose-response trend was observed showing higher IRRS was associated with worse OS (per quartile HR: 1.11, 95% CI: 1.01-1.22). Adding the E-DII to the model attenuated the association of IRRS with OS, and increasing E-DII, indicating a more pro-inflammatory diet, was associated with shorter OS (per quartile HR: 1.12, 95% CI: 1.02-1.24). Scoring high on both indices was associated with shorter OS (HR: 1.54, 95% CI: 1.16-2.06). CONCLUSION: Higher levels of inflammation-related exposures were associated with decreased EOC OS among Black women.

Archival single-cell genomics reveals persistent subclones during DCIS progression.

Ductal carcinoma in situ (DCIS) is a common precursor of invasive breast cancer. Our understanding of its genomic progression to recurrent disease remains poor, partly due to challenges associated with the genomic profiling of formalin-fixed paraffin-embedded (FFPE) materials. Here, we developed Arc-well, a high-throughput single-cell DNA-sequencing method that is compatible with FFPE materials. We validated our method by profiling 40,330 single cells from cell lines, a frozen tissue, and 27 FFPE samples from breast, lung, and prostate tumors stored for 3-31 years. Analysis of 10 patients with matched DCIS and cancers that recurred 2-16 years later show that many primary DCIS had already undergone whole-genome doubling and clonal diversification and that they shared genomic lineages with persistent subclones in the recurrences. Evolutionary analysis suggests that most DCIS cases in our cohort underwent an evolutionary bottleneck, and further identified chromosome aberrations in the persistent subclones that were associated with recurrence.