RESUMEN
BACKGROUND: Mucinous appendiceal adenocarcinomas (MAA) and non-mucinous appendiceal adenocarcinomas (NMAA) demonstrate differences in rates and patterns of recurrence, which may inform the appropriate extent of surgical resection (i.e., appendectomy versus colectomy). The impact of extent of resection on disease-specific survival (DSS) for each histologic subtype was assessed. PATIENTS AND METHODS: Patients with resected, non-metastatic MAA and NMAA were identified in the Surveillance, Epidemiology, and End Results database (2000-2020). Multivariable models were created to examine predictors of colectomy for each histologic subtype. DSS was calculated using Kaplan-Meier estimates and examined using Cox proportional hazards modeling. RESULTS: Among 4674 patients (MAA: n = 1990, 42.6%; NMAA: n = 2684, 57.4%), the majority (67.8%) underwent colectomy. Among colectomy patients, the rate of nodal positivity increased with higher T-stage (MAA: T1: 4.6%, T2: 4.0%, T3: 17.1%, T4: 21.6%, p < 0.001; NMAA: T1: 6.8%, T2: 11.4%, T3: 25.6%, T4: 43.8%, p < 0.001) and higher tumor grade (MAA: well differentiated: 7.7%, moderately differentiated: 19.2%, and poorly differentiated: 31.3%; NMAA: well differentiated: 9.0%, moderately differentiated: 20.5%, and 44.4%; p < 0.001). Nodal positivity was more frequently observed in NMAA (27.6% versus 16.4%, p < 0.001). Utilization of colectomy was associated with improved DSS for NMAA patients with T2 (log rank p = 0.095) and T3 (log rank p = 0.018) tumors as well as moderately differentiated histology (log rank p = 0.006). Utilization of colectomy was not associated with improved DSS for MAA patients, which was confirmed in a multivariable model for T-stage, grade, and use of adjuvant chemotherapy [hazard ratio (HR) 1.00, 95% confidence interval (CI) 0.81-1.22]. CONCLUSIONS: Colectomy was associated with improved DSS for patients with NMAA but not MAA. Colectomy for MAA may not be required.
Asunto(s)
Adenocarcinoma Mucinoso , Adenocarcinoma , Apendicectomía , Neoplasias del Apéndice , Colectomía , Programa de VERF , Humanos , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/cirugía , Neoplasias del Apéndice/mortalidad , Femenino , Masculino , Adenocarcinoma Mucinoso/cirugía , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/mortalidad , Persona de Mediana Edad , Anciano , Tasa de Supervivencia , Adenocarcinoma/cirugía , Adenocarcinoma/patología , Adenocarcinoma/mortalidad , Estudios de Seguimiento , Pronóstico , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , AdultoAsunto(s)
Adenocarcinoma Mucinoso , Neoplasias del Apéndice , Programa de VERF , Humanos , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/cirugía , Adenocarcinoma Mucinoso/cirugía , Adenocarcinoma Mucinoso/patología , Tasa de Supervivencia , Adenocarcinoma/cirugía , Adenocarcinoma/patología , Pronóstico , ApendicectomíaRESUMEN
BACKGROUND: Racial and ethnic disparities have been observed in the multidisciplinary management of pancreatic ductal adenocarcinoma. Intraductal papillary mucinous neoplasm is the most common identifiable precursor to pancreatic ductal adenocarcinoma, where early surgical intervention before the development of an invasive intraductal papillary mucinous neoplasm improves survival. The association of race/ethnicity with the risk of identifying invasive intraductal papillary mucinous neoplasms during resection has not been previously defined. METHODS: The American College of Surgeons National Quality Improvement Program targeted pancreatectomy database (2014-2021) was queried for patients with race/ethnicity data who underwent resection of an intraductal papillary mucinous neoplasm. Backward Wald logistic regression modeling (P ≤ 0.05 for entry; P > .10 for removal) was used to identify independent predictors of invasion. RESULTS: A total of 4,505 cases of resected intraductal papillary mucinous neoplasms were identified, with 923 (20.5%) demonstrating invasive intraductal papillary mucinous neoplasms. The cohort of individuals other than non-Hispanic Whites were significantly more likely to have invasive intraductal papillary mucinous neoplasms (White, 19.9%; Black, 24.2%; Asian, 23.7%; Hispanic, 22.6%; P = .026). Such disparity could not be explained by greater comorbidity, as non-White patients were significantly younger (age <65 years: 41.7% vs 33.2%, P < .001) and had better physical status (American Society of Anesthesiologists score ≤2: 28.8% vs 25.2%, P = .053). After controlling for clinicodemographic variables, being an individual of race/ethnicity other than White was independently associated with higher odds of invasive intraductal papillary mucinous neoplasms (odds ratio, 1.280; 95% confidence interval, 1.046-1.566; P = .017). No differences in postoperative morbidity were observed. CONCLUSION: In a national cohort of patients with resected intraductal papillary mucinous neoplasms, individuals who identified as being of race/ethnicity other than White were significantly more likely to have invasive intraductal papillary mucinous neoplasms during surgical resection.
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Carcinoma Ductal Pancreático , Neoplasias Quísticas, Mucinosas y Serosas , Neoplasias Pancreáticas , Humanos , Estados Unidos/epidemiología , Anciano , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Pancreatectomía , Conductos Pancreáticos/cirugía , Neoplasias Quísticas, Mucinosas y Serosas/cirugía , Invasividad Neoplásica , Estudios RetrospectivosRESUMEN
BACKGROUND: Several cytotoxic chemotherapies have demonstrated efficacy in improving recurrence-free survival (RFS) following resection of Stage II-IV colorectal cancer (CRC). However, the temporal dynamics of response to such adjuvant therapy have not been systematically quantified. METHODS: The Cochrane Central Register of Trials, Medline (PubMed) and Web of Science were queried from database inception to February 23, 2023 for Phase III randomized controlled trials (RCTs) where there was a significant difference in RFS between adjuvant chemotherapy and surgery only arms. Summary data were extracted from published Kaplan-Meier curves using DigitizeIT. Absolute differences in RFS event rates were compared at matched intervals using multiple paired t-tests. RESULTS: The initial search yielded 1469 manuscripts. After screening, 18 RCTs were eligible (14 Stage II/III; 4 Stage IV), inclusive of 16,682 patients. In the absence of adjuvant chemotherapy, the greatest rate of recurrence was observed in the first year (mean RFS event rate; 0-0.5 years: 0.22 ± 0.21; 0.5-1 years: 0.20 ± 0.09). Adjuvant chemotherapy was associated with significant decreases in the RFS event rates for the intervals 0-0.5 years (0.09 ± 0.09 vs. 0.22 ± 0.21, p < 0.001) and 0.5-1 years (0.14 ± 0.11 vs. 0.20 ± 0.09, p = 0.001) after randomization, but not at later intervals (1-5 years). In Stage IV trials, RFS event rates significantly differed for the interval 0-0.5 years (p = 0.012), corresponding with adjuvant treatment durations of 6 months. In Stage II/III trials, which included therapies of 6-24 months duration, there were marked differences in the RFS event rates between surgery and chemotherapy arms for the intervals 0-0.5 years (p < 0.001) and 0.5-1 years (p < 0.001) with smaller differences in the RFS event rates for the intervals 1-2 years (p = 0.012) and 2-3 years (p = 0.010). CONCLUSIONS: In a systematic review of positive RCTs comparing adjuvant chemotherapy to surgery alone for Stage II-IV CRC, observed RFS improvements were driven by early divergences that occurred primarily during active cytotoxic chemotherapy. Late recurrence dynamics were not influenced by adjuvant therapy use. Such observations may have implications for the use of chemotherapy for micrometastatic clones detectable by cell-free DNA-based methodologies.
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Neoplasias Colorrectales , Recurrencia Local de Neoplasia , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Quimioterapia Adyuvante/métodos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/patología , Estadificación de Neoplasias , Supervivencia sin Enfermedad , Ensayos Clínicos Fase III como AsuntoRESUMEN
Several molecular biomarkers have been identified to guide induction treatment selection for localized pancreatic ductal adenocarcinoma (PDAC). SMAD4 alterations and low GATA6 expression/modified "Moffitt" basal-like phenotype have each been associated with inferior survival uniquely for patients receiving 5-FU-based therapies. SMAD4 may directly regulate the expression of GATA6 in PDAC, pointing to a common predictive biomarker. To evaluate the relationship between SMAD4 mutations and GATA6 expression in human PDAC tumors, patients with paired SMAD4 mutation and GATA6 mRNA expression data in the TCGA and CPTAC were identified. In 321 patients (TCGA: n = 180; CPTAC: n = 141), the rate of SMAD4 alterations was 26.8%. The rate of SMAD4 alteration did not vary per tertile of normalized GATA6 expression (TCGA: p = 0.928; CPTAC: p = 0.828). In the TCGA, SMAD4 alterations and the basal-like phenotype were each associated with worse survival (log rank p = 0.077 and p = 0.080, respectively), but their combined presence did not identify a subset with uniquely inferior survival (p = 0.943). In the CPTAC, the basal-like phenotype was associated with significantly worse survival (p < 0.001), but the prognostic value was not influenced by the combined presence of SMAD4 alterations (p = 0.960). SMAD4 alterations were not associated with poor clinico-pathological features such as poor tumor grade, advanced tumor stage, positive lymphovascular invasion (LVI), or positive perineural invasion (PNI), compared with SMAD4-wildtype. Given that SMAD4 mutations were not associated with GATA6 expression or Moffitt subtype in two independent molecularly characterized PDAC cohorts, distinct biomarker-defined clinical trials are necessary.