Pancreatic cancer is a challenging disease with a low 5-year survival rate. There are areas for improvement in the tools used for screening, diagnosis, prognosis, treatment selection, and assessing ...treatment response. Liquid biopsy, particularly cell free DNA liquid biopsy, has shown promise as an adjunct to our standard care for pancreatic cancer patients, but has not yet been universally adopted into regular use by clinicians. In this publication, we aim to review cfDNA liquid biopsy in pancreatic cancer with an emphasis on current techniques, clinical utility, and areas of active investigation. We feel that researchers and clinicians alike should be familiar with this exciting modality as it gains increasing importance in the care of cancer patients.
Colorectal cancer (CRC) consensus molecular subtypes (CMS) have different immunological, stromal cell, and clinicopathological characteristics. Single-cell characterization of CMS subtype tumor ...microenvironments is required to elucidate mechanisms of tumor and stroma cell contributions to pathogenesis which may advance subtype-specific therapeutic development. We interrogate racially diverse human CRC samples and analyze multiple independent external cohorts for a total of 487,829 single cells enabling high-resolution depiction of the cellular diversity and heterogeneity within the tumor and microenvironmental cells.
Tumor cells recapitulate individual CMS subgroups yet exhibit significant intratumoral CMS heterogeneity. Both CMS1 microsatellite instability (MSI-H) CRCs and microsatellite stable (MSS) CRC demonstrate similar pathway activations at the tumor epithelial level. However, CD8+ cytotoxic T cell phenotype infiltration in MSI-H CRCs may explain why these tumors respond to immune checkpoint inhibitors. Cellular transcriptomic profiles in CRC exist in a tumor immune stromal continuum in contrast to discrete subtypes proposed by studies utilizing bulk transcriptomics. We note a dichotomy in tumor microenvironments across CMS subgroups exists by which patients with high cancer-associated fibroblasts (CAFs) and C1Q+TAM content exhibit poor outcomes, providing a higher level of personalization and precision than would distinct subtypes. Additionally, we discover CAF subtypes known to be associated with immunotherapy resistance.
Distinct CAFs and C1Q+ TAMs are sufficient to explain CMS predictive ability and a simpler signature based on these cellular phenotypes could stratify CRC patient prognosis with greater precision. Therapeutically targeting specific CAF subtypes and C1Q + TAMs may promote immunotherapy responses in CRC patients.
Background
Despite improvements, disparities in breast cancer care have led to an inequitable distribution of treatment delays and worse outcomes among patients with breast cancer. This study aimed ...to quantify the contribution of mediators that may explain racial/ethnic disparities in breast cancer treatment delays.
Patients and Methods
We conducted a retrospective analysis of patients from the National Cancer Database with stage I–III breast cancer who underwent surgical resection. Mediation analyses estimated the extent to which racial/ethnic disparities in the distribution of patient characteristics account for racial/ethnic disparities in delayed treatment.
Results
Of the 1,349,715 patients with breast cancer included, 10%, 5%, and 4% were Black, Hispanic, and other non-white race/ethnicity, respectively. Multivariable models showed that patients in these racial/ethnic groups had 73%, 81%, and 24% increased odds of having a treatment delay relative to white patients. Mediation analyses suggested that 15%, 19%, and 15% of the treatment delays among Black, Hispanic, and other non-white race/ethnicity patients, respectively, are explained by disparities in education, comorbidities, insurance, and facility type. Therefore, if these mediators had been distributed equally among all races/ethnicities, a reduction of 15–19% in the delayed treatment disparities experienced by minority patients would have been observed. Academic facility type was the factor that could yield the largest reduction in time to treatment disparities, contributing to 8–13% of racial/ethnic disparities.
Conclusions
Patients with breast cancer who identified as Black, Hispanic, and other non-white races/ethnicities are exposed to longer treatment delays relative to white patients. Efforts to equalize mediators could remove substantial portions of racial/ethnic disparities in delayed treatment.
Previous studies have demonstrated improved outcomes for patients with rectal cancer treated at higher-volume hospitals. However, little is known whether heterogeneity in this effect exists. The ...objective was to test whether the effect of increased annual rectal cancer resection volume on outcomes is consistent across all hospitals treating rectal cancer.
Adult stage I to III patients who underwent surgical resection for rectal adenocarcinoma from 2004 to 2016 were identified in the National Cancer Database.
We included 120,522 patients treated at 763 hospitals in this retrospective cohort study. Higher volume was linearly and incrementally related to outcomes in unadjusted analyses. In adjusted models, for an average patient at the average hospital, the effect of increasing the annual caseload of rectal cancer resections by 20 resections per year was associated with 8%, (hazard ratio = 0.92, 95% confidence interval = 0.87, 0.97), 18% (odds ratio = 0.82, 95% confidence interval = 0.70, 0.98), and 16% (odds ratio = 0.84, 95% confidence interval = 0.73, 0.95) relative reductions in 5-year overall survival, 30-, and 90-day mortality, respectively, and with a 19% (odds ratio = 1.19, 95% confidence interval = 1.04, 1.36) relative increase in the rate of neoadjuvant chemoradiation. These effects varied by individual hospitals such that 39% of hospitals do not see any benefit in 5-year overall survival associated with higher volumes. Increased volume was associated with lower positive circumferential resection margin rates at 19% of the hospitals.
This study confirms that higher-volume hospitals have improved outcomes after rectal cancer surgery. However, there exists significant variation in these effects induced by individual within-hospital effects. Regionalization policies may need to be flexible in identifying the hospitals that would achieve enhanced benefits from treating a larger volume of patients.
: General surgery residents often feel unprepared to perform pediatric surgery procedures since case volume and experience may be low. Previously, we successfully implemented a simulation-based ...training (SBT) module for placement of a silastic silo for gastroschisis. Therefore, we designed a single institution pilot study to assess whether SBT for placement of a percutaneous peritoneal drain for perforated necrotizing enterocolitis (NEC) was feasible and lead to skill acquisition and increased confidence.
: Our newly created NEC module within our pediatric surgery SBT curriculum for general surgery residents was used. Residents completed two simulation sessions three months apart with confidence testing before and after each session. Skill acquisition and performance were assessed using a standardized case scenario and procedure checklist. Changes in residents’ confidence and performance were determined using Wilcoxon Signed-Rank Tests.
: Nine post-graduate-year three general surgery residents completed this curriculum. Following completion, residents reported improved confidence completing each step of the procedure initially (p = 0.005) and at 3 months (p = 0.008) with improved technical scores (p = 0.011). The number of residents deemed proficient significantly improved (p = 0.031).
: Implementation of SBT module for perforated NEC was feasible and improved residents’ confidence and proficiency completing the procedure.
A new bibliometric index called the disruption score was recently proposed to identify innovative and paradigm-changing publications.
The goal was to apply the disruption score to the colorectal ...surgery literature to provide the community with a repository of important research articles.
This study is a bibliometric analysis.
The 100 most disruptive and developmental publications in Diseases of the Colon & Rectum, Colorectal Disease, International Journal of Colorectal Disease, and Techniques in Coloproctology were identified from a validated data set of disruption scores and linked with the iCite National Institutes of Health tool to obtain citation counts.
The primary outcomes measured were the disruption score and citation count.
We identified 12,127 articles published in Diseases of the Colon & Rectum (n = 8109), International Journal of Colorectal Disease (n = 1912), Colorectal Disease (n = 1751), and Techniques in Coloproctology (n = 355) between 1954 and 2014. Diseases of the Colon & Rectum had the most articles in the top 100 most disruptive and developmental lists. The disruptive articles were in the top 1% of the disruption score distribution in PubMed and were cited between 1 and 671 times. Being highly cited was weakly correlated with high disruption scores (r = 0.09). Developmental articles had disruption scores that were more strongly correlated with citation count (r = 0.18).
This study is subject to the limitations of bibliometric indices, which change over time.
The disruption score identified insightful and paradigm-changing studies in colorectal surgery. These studies include a wide range of topics and consistently identified editorials and case reports/case series as important research. This bibliometric analysis provides colorectal surgeons with a unique archive of research that can often be overlooked but that may have scholarly significance. See Video Abstract at http://links.lww.com/DCR/B639.UN NUEVO INDICE BIBLIOMÉTRICO: LAS 100 MAS IMPORTANTES PUBLICACIONES EN INNOVACIONES DESESTABILIZADORAS Y DE DESARROLLO EN LAS REVISTAS DE CIRUGÍA COLORRECTALANTECEDENTES:Un nuevo índice bibliométrico llamado innovación desestabilizadora y de desarrollo ha sido propuesto para identificar publicaciones de vanguardia y que pueden romper paradigmas.OBJETIVO:La meta fué aplicar el índice de desestabilización a la literature en cirugía colorectal para aportar a la comunidad con un acervo importante de artículos de investigación.DISEÑO:Un análisis bibliométrico.PARAMETROS:Las 100 publicaciones mas desestabilizadores y de desarrollo en las revistas: Diseases of the Colon and Rectum, Colorectal Disease, International Journal of Colorectal Disease, y Techniques in Coloproctology se recuperaron de una base de datos validada con puntuaciones de desestabilización y se ligaron con la herramienta iCite NIH para obtener la cuantificación de citas.PRINCIPAL MEDIDA DE RESULTADO:El índice desestabilizador y la cuantificación de citas.RESULTADOS:Se identificaron 12,127 articulos publicados en Diseases of the Colon and Rectum (n = 8,109), International Journal of Colorectal Disease (n = 1,912), Colorectal Disease (n = 1,751), y Techniques in Coloproctology (n = 355) de 1954-2014. Diseases of the Colon and Rectum representó la mayoría de las publicaciones dentro de la lista de los 100 mas desestabilizadores y de desarrollo. Esta literatura desestabilizadora se encuentra en el principal 1% de la distribución de la puntuacón desestabilizadora en PubMed y se citaron de 1 a 671 veces. El ser citado con frecuencia se relacionó vagamente con las puntuaciones de desastibilización (r = 0.09). Los artículos de desarrollo tuvieron puntuaciones de desestabilización que estuvieron muy correlacionados con la cuantificación de las citas (r = 0.18).LIMITACIONES:Las sujetas a las limitaciones de los índices bibliométricos, que se modifican en el tiempo.DISCUSION:La putuación de desestabilicación identificó trabajos perspicaces, pragmáticos y modificadores de paradigmas en cirugía colorrectal. Es de interés identificar que se incluyeron una gran variedad de temas y en forma consistente editoriales, reportes de casos y series de casos que representaron una investigación importante. Este análisis bibliométrico aporta a los cirujanos colorrectales de un acervo de investigación único que puede con frecuencia pasarse por alto, y sin embargo tener una gran importancia académica. Consulte Video Resumen en http://links.lww.com/DCR/B639. (Traducción- Dr. Miguel Esquivel-Herrera).
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