RESUMEN
CONTEXT: The role of cytoreduction of adrenocortical carcinoma (ACC) remains poorly understood. OBJECTIVE: To analyze the impact of cytoreductive surgery of the primary tumor in patients with metastatic ACC. DESIGN AND SETTING: We performed a multicentric, retrospective paired cohort study comparing the overall survival (OS) in patients with metastatic ACC who were treated either with cytoreductive surgery (CR group) or without cytoreductive surgery (no-CR group) of the primary tumor. Data were retrieved from 9 referral centers in the American-Australian-Asian Adrenal Alliance collaborative research group. PATIENTS: Patients aged ≥18 years with metastatic ACC at initial presentation who were treated between January 1, 1995, and May 31, 2019. INTERVENTION: Performance (or not) of cytoreductive surgery of the primary tumor. MAIN OUTCOME AND MEASURES: A propensity score match was done using age and the number of organs with metastasis (≤2 or >2). The main outcome was OS, determined from the date of diagnosis until death or until last follow-up for living patients. RESULTS: Of 339 patients pooled, 239 were paired and included: 128 in the CR group and 111 in the no-CR group. The mean follow-up was 67 months. Patients in the no-CR group had greater risk of death than did patients in the CR group (hazard ratio [HR] = 3.18; 95% CI, 2.34-4.32). Independent predictors of survival included age (HR = 1.02; 95% CI, 1.00-1.03), hormone excess (HR = 2.56; 95% CI, 1.66-3.92), and local metastasis therapy (HR = 0.41; 95% CI, 0.47-0.65). CONCLUSION: Cytoreductive surgery of the primary tumor in patients with metastatic ACC is associated with prolonged survival.
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Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Adolescente , Neoplasias de la Corteza Suprarrenal/cirugía , Carcinoma Corticosuprarrenal/cirugía , Adulto , Australia , Estudios de Cohortes , Procedimientos Quirúrgicos de Citorreducción , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND: Prognostic factors following index-cholecystectomy in patients with incidental gallbladder cancer (IGBC) are poorly understood. The aim of this study was to assess the value of the initial cystic duct margin status as a prognosticator factor and to aid in clinical decision making to move forward with curative intent oncologic extended resection (OER). METHODS: This retrospective study included patients with IGBC who underwent subsequent OER with curative intent at 2 centers (USA and Chile) between 1999 and 2016., Patients with and without evidence of residual cancer (RC) at OER were included. Pathologic features were examined, and predictors of overall survival (OS) were analyzed. RESULTS: The study included 179 patients. Thirty-three patients (17%) had a positive cystic duct margin at the index cholecystectomy. Forty-two patients (23%) underwent resection of the common bile duct. OS was significantly worse in the patients with a positive cystic duct margin at index cholecystectomy (OS rates at 5 years, 34% vs 57%; pâ¯=â¯0.032). Following multivariate analysis, only a positive cystic duct margin at index cholecystectomy was predictive of worse OS in patients with no evidence of residual cancer (RC) at OER (hazard ratio, 1.7 95%CI 1.04-2.78; pâ¯=â¯0.034). CONCLUSIONS: A positive cystic duct margin at index-cholecystectomy is a strong independent predictor of worse OS even if no further cancer is found at OER. In patients with positive cystic duct margin and no RC at OER common bile duct resection leads to improved outcomes.
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Colecistectomía/métodos , Conducto Cístico/diagnóstico por imagen , Conducto Cístico/cirugía , Neoplasias de la Vesícula Biliar/diagnóstico , Márgenes de Escisión , Neoplasia Residual/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Chile/epidemiología , Toma de Decisiones Clínicas , Femenino , Neoplasias de la Vesícula Biliar/mortalidad , Neoplasias de la Vesícula Biliar/cirugía , Humanos , Hallazgos Incidentales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasia Residual/diagnóstico , Neoplasia Residual/mortalidad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Tomografía Computarizada por Rayos X , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Conflicting data exists whether non-oncologic index cholecystectomy (IC) leading to discovery of incidental gallbladder cancer (IGBC) negatively impacts survival. This study aimed to determine whether a subgroup of patients derives a disadvantage from IC. METHODS: Patients with IGBC and non-IGBC treated at an academic USA and Chilean center during 1999-2016 were compared. Patients with T1, T4 tumor or preoperative jaundice were excluded. T2 disease was classified into T2a (peritoneal-side tumor) and T2b (hepatic-side tumor). Disease-specific survival (DSS) and its predictors were analyzed. RESULTS: Of the 196 patients included, 151 (77%) had IGBC. One hundred thirty-six (90%) patients of whom 118 (87%) had IGBC had T2 disease. Three-year DSS rates were similar between IGBC and non-IGBC for all patients. However, for T2b patients, 3-year survival rate was worse for IGBC (31% vs 85%; p = 0.019). In multivariate analysis of T2 patients, predictors of poor DSS were hepatic-side tumor hazard ratio [HR], 2.9; 95% CI, 1.6-5.4; p = 0.001) and N1 status (HR, 2.4; 95% CI, 1.6-3.6; p < 0.001). CONCLUSIONS: Patients with T2b gallbladder cancer specifically benefit from a single operation. These patients should be identified preoperatively and referred to hepatobiliary center.
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Colecistectomía/métodos , Neoplasias de la Vesícula Biliar/cirugía , Hallazgos Incidentales , Reoperación/estadística & datos numéricos , Centros Médicos Académicos , Adulto , Anciano , Anciano de 80 o más Años , Chile , Colecistectomía/mortalidad , Estudios de Cohortes , Bases de Datos Factuales , Supervivencia sin Enfermedad , Femenino , Neoplasias de la Vesícula Biliar/mortalidad , Neoplasias de la Vesícula Biliar/patología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Valores de Referencia , Estudios Retrospectivos , Medición de Riesgo , Estadísticas no Paramétricas , Tasa de Supervivencia , Resultado del Tratamiento , Estados UnidosRESUMEN
BACKGROUND: Gallbladder cancer detected incidentally after cholecystectomy (IGBC) currently is the most common diagnosis of gallbladder cancer, and oncologic extended resection (OER) is recommended for tumors classified higher than T1b. However, the precise prognostic significance of residual cancer (RC) found at the time of OER has not been well established. This analysis aimed to determine the prognostic impact of RC found in patients with IGBC undergoing OER. METHODS: Outcomes for IGBC at a center for a low-incidence country (USA) and a high-incidence country (Chile) between January 1999 and June 2015 were analyzed. Residual cancer was defined as histologically proven cancer at OER. Predictors of disease-specific survival (DSS) were analyzed. RESULTS: Of 187 patients, 171 (91.4%) achieved complete resection (R0) at OER. The rates of surgical mortality and severe morbidity were respectively 1.1 and 9.6%. Of the 187 patients, 73 (39%) had RC. Perineural invasion and/or lymphovascular invasion and T3 stage were associated with the presence of RC. In both countries, RC was associated with a significantly shorter median survival (23% vs not reached; p < 0.001) and lower 5-year DSS rate (19% vs. 74%; p < 0.001) despite R0 resection. In the multivariable analysis, RC was an independent poor predictor of DSS (hazard ratio [HR], 4.00; 95% confidence interval [CI], 2.13-7.47; p < 0.001), as were lymphovascular and/or perineural invasion (HR, 1.95; 95% CI, 1.19-3.21; p = 0.008). CONCLUSIONS: The presence of RC in patients undergoing OER for IGBC is associated with poor DSS in both high- and low-incidence countries, even when R0 resection is achieved. Residual cancer defines a high-risk cohort for whom adjuvant therapy may be beneficial.
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Colecistectomía/efectos adversos , Neoplasias de la Vesícula Biliar/cirugía , Hallazgos Incidentales , Recurrencia Local de Neoplasia/mortalidad , Neoplasia Residual/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Chile/epidemiología , Femenino , Estudios de Seguimiento , Neoplasias de la Vesícula Biliar/patología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/etiología , Neoplasia Residual/epidemiología , Neoplasia Residual/etiología , Pronóstico , Tasa de SupervivenciaRESUMEN
Crumbs family proteins are apical transmembrane proteins with ancient roles in cell polarity. Mouse Crumbs2 mutants arrest at midgestation with abnormal neural plate morphology and a deficit of mesoderm caused by defects in gastrulation. We identified an ENU-induced mutation, wsnp, that phenocopies the Crumbs2 null phenotype. We show that wsnp is a null allele of Protein O-glucosyltransferase 1 (Poglut1), which encodes an enzyme previously shown to add O-glucose to EGF repeats in the extracellular domain of Drosophila and mammalian Notch, but the role of POGLUT1 in mammalian gastrulation has not been investigated. As predicted, we find that POGLUT1 is essential for Notch signaling in the early mouse embryo. However, the loss of mouse POGLUT1 causes an earlier and more dramatic phenotype than does the loss of activity of the Notch pathway, indicating that POGLUT1 has additional biologically relevant substrates. Using mass spectrometry, we show that POGLUT1 modifies EGF repeats in the extracellular domain of full-length mouse CRUMBS2. CRUMBS2 that lacks the O-glucose modification fails to be enriched on the apical plasma membrane and instead accumulates in the endoplasmic reticulum. The data demonstrate that CRUMBS2 is the target of POGLUT1 for the gastrulation epithelial-to-mesenchymal transitions (EMT) and that all activity of CRUMBS2 depends on modification by POGLUT1. Mutations in human POGLUT1 cause Dowling-Degos Disease, POGLUT1 is overexpressed in a variety of tumor cells, and mutations in the EGF repeats of human CRUMBS proteins are associated with human congenital nephrosis, retinitis pigmentosa and retinal degeneration, suggesting that O-glucosylation of CRUMBS proteins has broad roles in human health.