The "Classification Pendulum" of Stage I Colorectal Cancer: A National Level Analysis of the Survival Difference Between T1 and T2 Colorectal Cancer.

BACKGROUND: The eighth edition of the American Joint Committee on Cancer classifies nonmetastatic, node-negative colorectal cancers invading the submucosa (T1) and muscularis propria (T2) as stage I tumors without additional subclassification. OBJECTIVE: The aim of the study was to compare survival of T1N0M0 versus T2N0M0 colorectal cancers and to investigate factors associated with decreased survival. DESIGN: This was an analysis of 2 large population-based data sets. SETTINGS: The study was conducted analyzing data from the Surveillance Epidemiology and End Result program and the National Cancer Database. PATIENTS: Adult patients undergoing major resection without additional therapy for stage I colorectal cancer were included. MAIN OUTCOME MEASURES: Overall and disease-specific survival for T1 versus T2 cancers were measured. Subgroup analyses by tumor location (colon versus rectum) were performed. RESULTS: A total of 30,228 (36.4% T1 and 63.6% T2) and 41,670 (41.1% T1 and 58.9% T2) patients were identified in the Surveillance Epidemiology and End Result database and the National Cancer Database. The 5-year overall survival rates were 87.1% and 86.2% for patients with T1 versus 82.7% and 80.7% for patients with T2 (p < 0.001) in the Surveillance Epidemiology and End Result database and the National Cancer Database. The 10-year overall survival rates were 71.3% and 66.3% for patients with T1 versus 62.2% and 57.2% for patients with T2 tumors (p < 0.001) in the Surveillance Epidemiology and End Result database and the National Cancer Database. The 5- and 10-year disease-specific survival for colorectal cancer in the Surveillance Epidemiology and End Result database was 97.0% (T1) versus 95.2% (T2) and 94.1% (T1) versus 90.3% (T2). Black race (HR = 1.26 and 1.65 for overall survival and disease-specific survival in the Surveillance Epidemiology and End Result database; HR = 1.20 for overall survival in the National Cancer Database) was associated with worse survival. LIMITATIONS: The study was limited by intrinsic biases related to large administrative data sets. CONCLUSIONS: Within stage I colorectal cancer, T2 tumors have decreased overall survival and disease-specific survival as compared with T1 cancers. This survival difference may justify revising the American Joint Committee on Cancer staging system to include the subclassification of stage Ia (T1N0M0) and stage Ib (T2N0M0). See Video Abstract at http://links.lww.com/DCR/B659. LA CLASIFICACIN PNDULO PARA EL CNCER COLORRECTAL EN ESTADIO I UN ANLISIS A NIVEL NACIONAL DE LA DIFERENCIA DE SOBREVIDA ENTRE EL CNCER COLORRECTAL T Y T: ANTECEDENTES:La octava edición del American Joint Committee on Cancer, clasifica los cánceres colorrectales no metastásicos con ganglios negativos, que invaden la submucosa (T1) y la muscularis propia (T2) como tumores en estadio I sin subclasificación adicional.OBJETIVO:El objetivo del estudio fue comparar la sobrevida de los cánceres colorrectales T1N0M0 versus T2N0M0 e investigar los factores asociados con la disminución de la sobrevida.DISEÑO:Análisis de dos grandes conjuntos de datos poblacionales.MARCO:El estudio se realizó analizando datos del Programa de Epidemiología de Vigilancia y Resultados Finales (SEER) y la Base de Datos Nacional del Cáncer.PACIENTES:Pacientes adultos en los cuales se realizó una resección mayor sin terapia adicional por cáncer colorrectal en estadio I.PRINCIPALES VARIABLES ANALIZADAS:Sobrevida global y específica de la enfermedad para los cánceres T1 versus T2. Se realizó un análisis de subgrupos según la ubicación del tumor (colon versus recto).RESULTADOS:Se incluyeron un total de 30.228 (36,4% T1 y 63,6% T2) y 41.670 (41,1% T1 y 58,9% T2) pacientes en las bases de datos SEER y la Base de Datos Nacional del Cáncer, respectivamente. La sobrevida global a 5 años fue del 87,1% y el 86,2% para los pacientes con T1 frente al 82,7% y el 80,7% de los pacientes con T2 (p < 0,001) en el SEER y la Base de Datos Nacional del Cáncer, respectivamente. La sobrevida global a 10 años fue del 71,3% y el 66,3% para los pacientes con T1 frente al 62,2% y el 57,2% de los pacientes con tumores T2 (p < 0,001) en el SEER y la Base de Datos Nacional del Cáncer, respectivamente. La sobrevida específica de la enfermedad a 5 y 10 años para el cáncer colorrectal en el SEER fue del 97,0% (T1) frente al 95,2% (T2) y del 94,1% (T1) frente al 90,3% (T2), respectivamente. La grupo étnico afroamericano se asoció con una sobrevida menor (Hazard Ratio -HR 1,26 y 1,65 para la sobrevida general y sobrevida específica de la enfermedad-SEER; HR 1,20 para la sobrevida general-Base de de Datos Nacional del Cáncer).LIMITACIONES:Sesgos intrínsecos relacionados con el análisis de grandes conjuntos de datos.CONCLUSIONES:Dentro del cáncer colorrectal en estadio I, los tumores T2 han disminuido la sobrevida general y la sobrevida específica de la enfermedad, en comparación con los cánceres T1. Esta diferencia de sobrevida puede justificar la revisión del sistema de estadificación del American Joint Committee on Cancer para incluir la subclasificación del estadio Ia (T1N0M0) y el estadio Ib (T2N0M0). Consulte Video Resumen en http://links.lww.com/DCR/B659.

Impact of minimally invasive gastrectomy on use of and time to adjuvant chemotherapy for gastric adenocarcinoma.

BACKGROUND: Chemotherapy improves outcomes in patients with resectable gastric cancer. Minimally invasive gastrectomy (MIS) rates are increasing, though the impact of MIS on postoperative chemotherapy remains uncertain. This study examines the impact of MIS vs open gastrectomy (OG) on utilization of adjuvant chemotherapy for high-risk gastric cancer. METHODS: Patients in the National Cancer Database who underwent resection for high-risk gastric adenocarcinoma between 2010 and 2015 were included. Patients were stratified by surgical approach (MIS vs OG) and analyzed using multivariable regression modeling. Primary endpoints were utilization of and time to initiation of adjuvant chemotherapy. RESULTS: Overall, 23 071 patients were included; 16 595 (71.9%) underwent OG and 6476 (28.1%) underwent MIS. After adjusting for patient and tumor characteristics, MIS was not associated with increased use of adjuvant chemotherapy (odds ratio [OR]: 1.027, 95% confidence interval [CI]: 0.95 to 1.11, P = .50), and time to initiation of chemotherapy was similar (-2% change, 95% CI: -5% to +1%, P = .27). MIS was associated with shorter hospital stays (-1 day). Thirty-day readmission rates, 90-day mortality, and overall survival were similar between groups. CONCLUSIONS: In this study, while MIS for gastric adenocarcinoma was associated with shorter hospital stays and comparable survival, it was not associated with improved utilization or time to initiation of adjuvant chemotherapy.

Comparative outcomes of treatment modalities in nonagenarians with nonmetastatic pancreatic adenocarcinoma.

BACKGROUND: There has been an increase in the elderly patient population seeking care for pancreatic ductal adenocarcinoma (PDAC). This study aimed to delineate the effectiveness of therapeutic options in nonagenarians (aged 90-99 years) diagnosed with resectable PDAC. METHODS: This study used the National Cancer Database to identify patients with nonmetastatic PDAC (stage I-III) from 2004 to 2021. The study compared median overall survival (mOS) using Kaplan-Meier curves among 5 treatment categories: surgery, surgery along with chemoradiation, chemotherapy alone, radiotherapy alone, and chemoradiation alone. Cox proportional hazards regression was used in multivariate analyses. RESULTS: Of 459,174 patients, 793 aged ≥ 90 years had nonmetastatic PDAC. Of 793 patients, 245 (30.9 %) underwent chemotherapy alone, 296 (37.3 %) underwent radiotherapy alone, 162 (20.4 %) underwent chemoradiation alone, 58 (7.3 %) underwent curative-intent resection, and 32 (4.0 %) underwent surgery combined with chemoradiation. The mOS estimates in different treatment modalities were 9.5 months (95 % CI, 6.7-14.5) for surgery alone, 19.1 months (95 % CI, 2.4-64.3) for surgery combined with chemoradiation, 8.2 months (95 % CI, 7.2-9.2) for chemotherapy alone, 8.4 months (95 % CI, 7.6-9.6) for radiotherapy alone, and 11.2 months (95 % CI, 8.7-12.9) for chemoradiation alone (P < .001). In multivariate analysis, the odds of survival were better for patients who underwent surgery alone than for those who underwent chemotherapy alone, although the odds of survival did not significantly differ between patients who underwent radiotherapy alone and those who underwent chemoradiation alone. Nonetheless, surgery combined with chemoradiation was associated with decreased mortality risk compared with surgery alone (hazard ratio, 0.46; 95 % CI, 0.25-0.87; P = .02). Operative 30-day mortality rate was 8.8 %, and 90-day mortality rate was 17.8 %. CONCLUSION: Surgery combined with chemoradiation improved the survival of nonagenarians with PDAC compared with other therapies. However, only 1 in 25 patients received all 3 treatment components. Moreover, our study highlights a very high operative mortality rate in nonagenarians.

Krt14 and Krt15 differentially regulate regenerative properties and differentiation potential of airway basal cells.

Keratin expression dynamically changes in airway basal cells (BCs) after acute and chronic injury, yet the functional consequences of these changes on BC behavior remain unknown. In bronchiolitis obliterans (BO) after lung transplantation, BC clonogenicity declines, which is associated with a switch from keratin15 (Krt15) to keratin14 (Krt14). We investigated these keratins' roles using Crispr-KO in vitro and in vivo and found that Krt14-KO and Krt15-KO produce contrasting phenotypes in terms of differentiation and clonogenicity. Primary mouse Krt14-KO BCs did not differentiate into club and ciliated cells but had enhanced clonogenicity. By contrast, Krt15-KO did not alter BC differentiation but impaired clonogenicity in vitro and reduced the number of label-retaining BCs in vivo after injury. Krt14, but not Krt15, bound the tumor suppressor stratifin (Sfn). Disruption of Krt14, but not of Krt15, reduced Sfn protein abundance and increased expression of the oncogene dNp63a during BC differentiation, whereas dNp63a levels were reduced in Krt15-KO BCs. Overall, the phenotype of Krt15-KO BCs contrasts with Krt14-KO phenotype and resembles the phenotype in BO with decreased clonogenicity, increased Krt14, and decreased dNp63a expression. This work demonstrates that Krt14 and Krt15 functionally regulate BC behavior, which is relevant in chronic disease states like BO.

Development and characterization of ferret ex vivo tracheal injury and cell engraftment model.

The field of airway biology research relies primarily on in vitro and in vivo models of disease and injury. The use of ex vivo models to study airway injury and cell-based therapies remains largely unexplored although such models have the potential to overcome certain limitations of working with live animals and may more closely replicate in vivo processes than in vitro models can. Here, we characterized a ferret ex vivo tracheal injury and cell engraftment model. We describe a protocol for whole-mount staining of cleared tracheal explants, and showed that it provides a more comprehensive structural overview of the surface airway epithelium (SAE) and submucosal glands (SMGs) than 2D sections, revealing previously underappreciated structural anatomy of tracheal innervation and vascularization. Using an ex vivo model of tracheal injury, we evaluated the injury responses in the SAE and SMGs that turned out to be consistent with published in vivo work. We used this model to assess factors that influence engraftment of transgenic cells, providing a system for optimizing cell-based therapies. Finally, we developed a novel 3D-printed reusable culture chamber that enables live imaging of tracheal explants and differentiation of engrafted cells at an air-liquid interface. These approaches promise to be useful for modeling pulmonary diseases and testing therapies. Graphical abstract1,2. We describe here a method for differential mechanical injury of ferret tracheal explants that can be used to evaluate airway injury responses ex vivo. 3. Injured explants can be cultured at ALI (using the novel tissue-transwell device on the right) and submerged long-term to evaluate tissue-autonomous regeneration responses. 4. Tracheal explants can also be used for low throughput screens of compounds to improve cell engraftment efficiency or can be seeded with particular cells to model a disease phenotype. 5. Lastly, we demonstrate that ex vivo-cultured tracheal explants can be evaluated by various molecular assays and by immunofluorescent imaging that can be performed live using our custom-designed tissue-transwell.

Psychosocial Assessment of Candidates for Transplantation (PACT) Score Identifies High Risk Patients in Pediatric Renal Transplantation.

Background: Currently, there is no standardized approach for determining psychosocial readiness in pediatric transplantation. We examined the utility of the Psychosocial Assessment of Candidates for Transplantation (PACT) to identify pediatric kidney transplant recipients at risk for adverse clinical outcomes. Methods: Kidney transplant patients <21-years-old transplanted at Duke University Medical Center between 2005 and 2015 underwent psychosocial assessment by a social worker with either PACT or unstructured interview, which were used to determine transplant candidacy. PACT assessed candidates on a scale of 0 (poor candidate) to 4 (excellent candidate) in areas of social support, psychological health, lifestyle factors, and understanding. Demographics and clinical outcomes were analyzed by presence or absence of PACT and further characterized by high (≥3) and low (≤2) scores. Results: Of 54 pediatric patients, 25 (46.3%) patients underwent pre-transplant evaluation utilizing PACT, while 29 (53.7%) were not evaluated with PACT. Patients assessed with PACT had a significantly lower percentage of acute rejection (16.0 vs. 55.2%, p = 0.007). After adjusting for HLA mismatch, a pre-transplant PACT score was persistently associated with lower odds of acute rejection (Odds Ratio 0.119, 95% Confidence Interval 0.027-0.52, p = 0.005). In PACT subsection analysis, the lack of family availability (OR 0.08, 95% CI 0.01-0.97, p = 0.047) and risk for psychopathology (OR 0.34, 95% CI 0.13-0.87, p = 0.025) were associated with a low PACT score and post-transplant non-adherence. Conclusions: Our study highlights the importance of standardized psychosocial assessments and the potential use of PACT in risk stratifying pre-transplant candidates.