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BACKGROUND AND OBJECTIVES: In 2003, the Society of Surgical Oncology (SSO) initiated a breast surgical oncology fellowship, which has now grown to 60 SSO accredited programs as of 2021. Limited knowledge exists on the traits of successful applicants and the factors influencing the rank list. METHODS: A web-based, anonymous survey was sent to all SSO Breast Surgical Oncology Fellowship program directors. The survey consisted of 26 questions. Descriptive statistics were used to analyze survey responses and evaluate impact on applicant interview and rank list. RESULTS: Thirty-four programs (57% response rate) completed the survey. Programs received an average of 70 applications and granted 24 interviews. Most programs reported a minimum ABSITE cut-off score (n = 28, 82%) and a defined publication requirement (n = 22, 65%), including a first-author requirement (n = 18, 53%) to extend an invitation to interview. For postinterview rank, applicant interpersonal skills were highly valued. The interview was the most important aspect for the rank list. CONCLUSIONS: Many programs have ABSITE and publication thresholds before offering an interview. Upon receiving interview invitation, the applicant's interview performance, interpersonal skills, and letters of recommendation were the most important aspect in rank list decision making.
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Internado y Residencia , Oncología Quirúrgica , Humanos , Becas , Encuestas y CuestionariosRESUMEN
BACKGROUND AND OBJECTIVES: Guidelines for Stage II colon cancer recommend adjuvant chemotherapy (AC) only for tumors with high-risk features, but long-term outcomes data are mixed. We aimed to determine if AC was associated with a survival benefit in this population. METHODS: Patients were identified from the National Cancer Database and included if they met the following criteria: diagnosis of Stage II colon cancer, surgery, survival data, and complete data on six high-risk features. The cohort of 57 335 patients was stratified by receipt of AC. Subgroup analysis was performed on patients under the age of 65 years with no comorbidities. Overall survival (OS) was the primary endpoint. RESULTS: An increasing number of high-risk features was associated with significantly decreased median OS. AC was associated with significantly increased OS for patients with 0, 1, 2, and ≥3 high-risk features. On subgroup analysis, receipt of AC was associated with a reduced risk of death (hazard ratio: 0.66; confidence interval: 0.59-0.74). For patients in the subgroup who had a T4 tumor, AC was associated with increased OS (92.7 vs. 83.6 months). CONCLUSIONS: AC should be considered for all younger, healthy patients with Stage II colon cancer and may be associated with a survival benefit for patients with T4 disease.
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Neoplasias del Colon , Anciano , Quimioterapia Adyuvante , Estudios de Cohortes , Neoplasias del Colon/patología , Humanos , Estadificación de Neoplasias , Modelos de Riesgos ProporcionalesAsunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Neoplasias Hepáticas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Conductos Biliares Intrahepáticos , Colangiocarcinoma/tratamiento farmacológico , Arteria Hepática , Humanos , Bombas de Infusión Implantables , Infusiones Intraarteriales , Neoplasias Hepáticas/tratamiento farmacológico , Resultado del TratamientoAsunto(s)
Neoplasias de la Mama , Ganglio Linfático Centinela , Axila/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Terapia Neoadyuvante , Estadificación de Neoplasias , Ganglio Linfático Centinela/patología , Biopsia del Ganglio Linfático CentinelaAsunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Acrilamidas , Compuestos de Anilina , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/terapia , Receptores ErbB/genética , Humanos , Indoles , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Mutación , PirimidinasAsunto(s)
Melanoma , Neoplasias Cutáneas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Humanos , Ipilimumab/uso terapéutico , Melanoma/tratamiento farmacológico , Melanoma/patología , Terapia Neoadyuvante , Nivolumab/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), has also recently shown efficacy in the treatment of lung cancers with ROS1 translocations. Resistance to crizotinib developed in a patient with metastatic lung adenocarcinoma harboring a CD74-ROS1 rearrangement who had initially shown a dramatic response to treatment. We performed a biopsy of a resistant tumor and identified an acquired mutation leading to a glycine-to-arginine substitution at codon 2032 in the ROS1 kinase domain. Although this mutation does not lie at the gatekeeper residue, it confers resistance to ROS1 kinase inhibition through steric interference with drug binding. The same resistance mutation was observed at all the metastatic sites that were examined at autopsy, suggesting that this mutation was an early event in the clonal evolution of resistance. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00585195.).
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Adenocarcinoma/genética , Resistencia a Medicamentos/genética , Neoplasias Pulmonares/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Pirazoles/uso terapéutico , Piridinas/uso terapéutico , Translocación Genética , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Crizotinib , Resultado Fatal , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Mutación , Conformación Proteica , Proteínas Tirosina Quinasas/química , Proteínas Proto-Oncogénicas/química , Relación Estructura-ActividadAsunto(s)
Neoplasias Colorrectales , Hipertermia Inducida , Neoplasias Peritoneales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneales/tratamiento farmacológicoRESUMEN
Cancer cells engage in a metabolic program to enhance biosynthesis and support cell proliferation. The regulatory properties of pyruvate kinase M2 (PKM2) influence altered glucose metabolism in cancer. The interaction of PKM2 with phosphotyrosine-containing proteins inhibits enzyme activity and increases the availability of glycolytic metabolites to support cell proliferation. This suggests that high pyruvate kinase activity may suppress tumor growth. We show that expression of PKM1, the pyruvate kinase isoform with high constitutive activity, or exposure to published small-molecule PKM2 activators inhibits the growth of xenograft tumors. Structural studies reveal that small-molecule activators bind PKM2 at the subunit interaction interface, a site that is distinct from that of the endogenous activator fructose-1,6-bisphosphate (FBP). However, unlike FBP, binding of activators to PKM2 promotes a constitutively active enzyme state that is resistant to inhibition by tyrosine-phosphorylated proteins. These data support the notion that small-molecule activation of PKM2 can interfere with anabolic metabolism.
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Biopolímeros/metabolismo , Transformación Celular Neoplásica , Activadores de Enzimas/farmacología , Piruvato Quinasa/metabolismo , Animales , Biopolímeros/química , Western Blotting , Proliferación Celular , Humanos , Ratones , Neoplasias/enzimología , Neoplasias/metabolismo , Neoplasias/patología , Piruvato Quinasa/químicaRESUMEN
The echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion oncogene represents a molecular target in a small subset of non-small cell lung cancers (NSCLCs). This fusion leads to constitutive ALK activation with potent transforming activity. In a pivotal phase 1 clinical trial, the ALK tyrosine kinase inhibitor (TKI) crizotinib (PF-02341066) demonstrated impressive antitumor activity in the majority of patients with NSCLC harboring ALK fusions. However, despite these remarkable initial responses, cancers eventually develop resistance to crizotinib, usually within 1 y, thereby limiting the potential clinical benefit. To determine how cancers acquire resistance to ALK inhibitors, we established a model of acquired resistance to crizotinib by exposing a highly sensitive EML4-ALK-positive NSCLC cell line to increasing doses of crizotinib until resistance emerged. We found that cells resistant to intermediate doses of crizotinib developed amplification of the EML4-ALK gene. Cells resistant to higher doses (1 µM) also developed a gatekeeper mutation, L1196M, within the kinase domain, rendering EML4-ALK insensitive to crizotinib. This gatekeeper mutation was readily detected using a unique and highly sensitive allele-specific PCR assay. Although crizotinib was ineffectual against EML4-ALK harboring the gatekeeper mutation, we observed that two structurally different ALK inhibitors, NVP-TAE684 and AP26113, were highly active against the resistant cancer cells in vitro and in vivo. Furthermore, these resistant cells remained highly sensitive to the Hsp90 inhibitor 17-AAG. Thus, we have developed a model of acquired resistance to ALK inhibitors and have shown that second-generation ALK TKIs or Hsp90 inhibitors are effective in treating crizotinib-resistant tumors harboring secondary gatekeeper mutations.
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Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , Proteínas de Fusión Oncogénica/genética , Pirazoles/farmacología , Piridinas/farmacología , Animales , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Crizotinib , Cartilla de ADN/genética , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Humanos , Immunoblotting , Hibridación Fluorescente in Situ , Ratones , Ratones Desnudos , Mutación/genética , Proteínas de Fusión Oncogénica/antagonistas & inhibidores , Compuestos Organofosforados/farmacología , Fosforilación/efectos de los fármacos , Pirazoles/uso terapéutico , Piridinas/uso terapéutico , Pirimidinas/farmacología , ARN Interferente Pequeño/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacos , Análisis de Supervivencia , TransfecciónRESUMEN
INTRODUCTION: We evaluate National Institutes of Health (NIH) data to describe endocrine surgical research performed by surgeons in the United States. METHODS: An internal NIH database was queried for endocrine surgery-related grants awarded to surgeons in 2010, 2015, and 2020. The grants were then compared based on cost, grant type, research type, and endocrine topic. RESULTS: Eighteen grants ($6.4 M) focused on endocrine surgery-related research topics were identified in 2020, 17 ($7.3 M) in 2015, and 11 ($3.8 M) in 2010. In 2020, 14 grants were basic science and 4 were clinical outcomes, and pancreatic endocrine disease and thyroid disease each comprised 6 grants. R01 and R21 grants comprised 10 (55.6%) of the grants in 2020, compared to 10 (58.5%) in 2015 and 8 (72.7%) in 2010, while K08 and K23 grants increased to 4 (22.2%) in 2020 from 2 (11.8%) in 2015 and none in 2010. CONCLUSION: There were more K-awards focused on endocrine surgery-related research in 2020 compared to 2015 and 2010, suggesting the pipeline is growing.
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Distinciones y Premios , Investigación Biomédica , Cirujanos , Humanos , Estados Unidos , National Institutes of Health (U.S.) , Bases de Datos FactualesRESUMEN
Peripheral neuropathy is a common side effect of a number of pharmaceutical compounds, including several chemotherapy drugs. Among these are vincristine sulfate, a mitotic inhibitor used to treat a variety of leukemias, lymphomas, and other cancers, and bortezomib, a 26S proteasome inhibitor used primarily to treat relapsed multiple myeloma and mantle cell lymphoma. To gain insight into the mechanisms by which these compounds act, we tested their effects in zebrafish. Vincristine or bortezomib given during late embryonic development caused significant defects at both behavioral and cellular levels. Intriguingly, the effects of the two drugs appear to be distinct. Vincristine causes uncoordinated swimming behavior, which is coupled with a reduction in the density of sensory innervation and overall size of motor axon arbors. Bortezomib, in contrast, increases the duration and amplitude of muscle contractions associated with escape swimming, which is coupled with a preferential reduction in fine processes and branches of sensory and motor axons. These results demonstrate that zebrafish is a convenient in vivo assay system for screening potential pharmaceutical compounds for neurotoxic side effects, and they provide an important step toward understanding how vincristine and bortezomib cause peripheral neuropathy.
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Antineoplásicos/efectos adversos , Axones/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Ácidos Borónicos/efectos adversos , Pirazinas/efectos adversos , Vincristina/efectos adversos , Animales , Axones/patología , Bortezomib , Inmunohistoquímica , Larva/efectos de los fármacos , Pez CebraRESUMEN
BACKGROUND: Post-operative pancreatic fistula (POPF) is a serious complication following pancreas surgery. We aimed to establish factors associated with POPF specifically in patients with pancreatic neuroendocrine tumors (PNET). METHODS: The 2014-2018 American College of Surgeons National Surgical Quality Improvement Program database was querried for patients undergoing resection for PNET. The impact of patient, tumor, and operative factors on POPF formation was evaluated. RESULTS: 3532 patient underwent resections for PNET. The POPF rate was significantly higher in patients with PNET (24.8%) versus non-PNET (16.4%) (p < 0.0001). Male sex (OR 1.45, 95% CI 1.11-1.89), enucleation (OR 3.14, 95% CI 1.10-8.98), pancreaticoduodenectomy (OR 1.51, 95% CI 1.13-2.03), small duct size <3 mm (OR 3.24, 95% CI 1.62-6.48), and soft gland texture (OR 1.81, 95% CI 1.18-2.77) were independently associated with POPF in PNET patients on multivariable analysis. CONCLUSIONS: POPF is more common in patients undergoing resection for PNET and is dictated primarily by surgical approach and gland characteristics.
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Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Masculino , Fístula Pancreática/epidemiología , Fístula Pancreática/etiología , Mejoramiento de la Calidad , Tumores Neuroendocrinos/cirugía , Tumores Neuroendocrinos/patología , Pancreaticoduodenectomía/efectos adversos , Páncreas/cirugía , Complicaciones Posoperatorias/etiología , Neoplasias Pancreáticas/patología , Factores de Riesgo , Estudios RetrospectivosRESUMEN
Wild-type KIT and PDGFRA gastrointestinal stromal tumors (GIST) are rare tumors with limited treatment options. We sought to determine the clinicopathologic features of wild-type GIST and identify factors that influence overall survival (OS) using a large national database. Retrospective evaluation of patients with wild-type GIST in the National Cancer Database (NCDB) was performed. Demographic, clinicopathologic, and treatment data were analyzed. Features associated with OS were investigated using Kaplan-Meier analysis and Cox proportional hazards model. 244 patients with median diagnosis age of 59 years (95% CI 57-63) were identified. The stomach was the most common primary site (57%) followed by the small intestine (35%). Surgical resection was performed on 85% of patients and 53% of patients received systemic therapy. Factors associated with decreased OS on multivariable analysis included small intestine primary (HR 2.72, 95% CI 1.13-6.69, P = 0.026) and > 5 mitoses per 50 HPF (HR 4.77, 95% CI 1.86-13.2, P = 0.001). Wild-type GISTs may be identified in older patients, with most arising in the stomach and small bowel. Surgery remains the principal treatment modality. Small intestine primary site and high mitotic count were associated with abbreviated OS.
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Tumores del Estroma Gastrointestinal , Anciano , Demografía , Tumores del Estroma Gastrointestinal/epidemiología , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Intestino Delgado/patología , Intestino Delgado/cirugía , Estimación de Kaplan-Meier , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Small bowel neuroendocrine tumors (SB-NET) frequently metastasize to regional lymphatic or distant sites. Although most prognostication of SB-NET focuses on lymph node involvement, findings from studies of neuroendocrine tumors from other primary sites have suggested that preoperative serum chromogranin-A (CgA) levels may provide a more accurate metric. METHODS: Using the National Cancer Database (2004-2016), we analyzed patients with locoregional SB-NET who underwent curative resection including an adequate lymphadenectomy (n = 1,274). A statistically optimized cut-point was used to dichotomize CgA cohort based on preoperative serum CgA levels. RESULTS: We determined that a CgA ≥139 ng/mL identified patients with significantly shorter estimated mean overall survival (6.6 years vs 7.6 years, log-rank P = .00001). These patients were also older (63 vs 57 years, P < .001) and had higher rates of poorly differentiated tumors (2.1% vs 0.7%, P = .04) or primary tumors >1 cm (88.2% vs 79.2%, P = .001). Clinical features associated with shorter overall survival included preoperative CgA ≥139 ng/mL (HR = 2.19, 95% CI 1.22-3.92; P = .009), age at diagnosis (HR = 1.06, 95% CI 1.03-1.09; P < .001), Charlson-Deyo score ≥2 (HR = 3.93, 95% CI 1.71-9.01; P = .001), and poorly differentiated tumors (HR = 11.22, 95% CI 4.16-30.24; P < .001). Neither lymph node metastasis nor T-stage were independently associated with shorter overall survival in patients with locoregional SB-NET. CONCLUSION: Elevated preoperative serum CgA is an adverse prognostic marker associated with shorter overall survival in patients with locoregional SB-NET.