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PURPOSE: The ACOSOG Z0011 (Z11) trial assessed the benefit of axillary dissection (ALND) for breast cancer patients with sentinel lymph node (SLN) metastases; however, Z11 excluded patients with ≥ 3 positive SLNs. We analyzed trends in ALND omission in patients with ≥ 3 positive SLNs. METHODS: Women with ≥ 3 positive SLNs who underwent breast-conserving surgery (BCS) or mastectomy between 2018 and 2020 in the National Cancer Database were included using SLN codes initiated in 2018. Patients with stage IV disease, recurrent breast cancer, and who underwent neoadjuvant chemotherapy were excluded. A multivariable logistic regression model was utilized to determine the proportion who received ALND and factors associated with ALND omission. A subgroup analysis was performed among patients who met the remainder of the Z11 inclusion criteria (BCS, T1/T2 breast cancer). RESULTS: We identified 3654 patients with ≥ 3 positive SLNs. ALND was omitted in 37% of patients, and omission significantly increased from 2018 to 2020 (29% vs. 41%, p < 0.0001). Older age, lower grade tumors, no radiation, non-academic facility, BCS, more SLNs examined and fewer positive SLNs were significantly associated with ALND omission. 942 patients with ≥ 3 positive SLNs met the remainder of the Z11 inclusion criteria. ALND was omitted in 49% of these patients, and omission increased from 2018 to 2020 (44% vs. 49%, p = 0.22). CONCLUSION: Approximately one-third of patients with ≥ 3 positive SLNs do not undergo ALND; omission of ALND increased from 2018 to 2020. Studies assessing oncologic outcomes of patients with ≥ 3 positive SLNs who do and do not receive ALND are required.
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Axila , Neoplasias de la Mama , Escisión del Ganglio Linfático , Biopsia del Ganglio Linfático Centinela , Ganglio Linfático Centinela , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Persona de Mediana Edad , Ganglio Linfático Centinela/patología , Ganglio Linfático Centinela/cirugía , Escisión del Ganglio Linfático/métodos , Anciano , Biopsia del Ganglio Linfático Centinela/métodos , Adulto , Metástasis Linfática , Mastectomía Segmentaria/métodos , Mastectomía/métodos , Estudios RetrospectivosRESUMEN
INTRODUCTION: Up to 90% of patients undergo inadequate resection for incidentally diagnosed T1b-T3 gallbladder cancer (GBC). We evaluated whether adjuvant therapies (ATs) are associated with prolonged overall survival (OS) for patients undergoing inadequate resection of T1b-T3 GBC. METHODS: Patients who underwent inadequate resection, defined as simple cholecystectomy, for T1b-T3, Nx-N2, and M0 GBC were identified from the National Cancer Database (2004-2016). Patient characteristics, variables associated with AT use, and OS were described using the chi-square test, multivariable logistical regression, Kaplan-Meier, and Cox proportional hazard models. RESULTS: Of 1386 patients who met inclusion criteria, most received no AT (64%), 20% received chemotherapy (CT), and 16% received chemoradiotherapy (CRT). Patients who received no AT were generally older (51% ≥ 75 y) and had no comorbidities (65% Charlson Comorbidity Index 0). Among those who received AT, CRT rather than CT, tended to be employed for patients who were older (≥75 y) or had more comorbidities (Charlson Comorbidity Index ≥1). Patients with advanced disease (T3, positive lymph nodes, or positive margins) were more likely to receive CRT. For T1b-T3 GBC, any AT was associated with prolonged median OS compared to no AT (22 months versus 15 mo, P < 0.01). Relative to no AT, CT (hazard ratio 0.76, 95% confidence interval 0.67-0.92) and CRT (0.59, 95% confidence interval 0.49-0.72) were associated with decreased risk of death. CONCLUSIONS: AT was associated with prolonged OS for patients with inadequately resected T1b-T3 GBC. CRT may have a role in treatment for patients with high-risk disease following inadequate resection of T1b-T3 GBC.
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BACKGROUND: Patients with estrogen receptor (ER)-positive, HER2-negative breast cancer (BC), and high-risk 21-gene recurrence score (RS) results benefit from chemotherapy. We evaluated chemotherapy refusal and survival in healthy older women with high-RS, ER-positive BC. METHODS: Retrospective review of the National Cancer Database (2010-2017) identified women ≥ 65 years of age, with ER-positive, HER2-negative, high-RS (≥ 26) BC. Patients with Charlson Comorbidity Index ≥ 1, stage III/IV disease, or incomplete data were excluded. Women were compared by chemotherapy receipt or refusal using the Cochrane-Armitage test, multivariable logistical regression modeling, the Kaplan-Meier method, and Cox's proportional hazards modeling. RESULTS: 6827 women met study criteria: 5449 (80%) received chemotherapy and 1378 (20%) refused. Compared to women who received chemotherapy, women who refused were older (71 vs 69 years), were diagnosed more recently (2014-2017, 67% vs 61%), and received radiation less frequently (67% vs 71%) (p ≤ 0.05). Refusal was associated with decreased 5-year OS for women 65-74 (92% vs 95%) and 75-79 (85% vs 92%) (p ≤ 0.05), but not for women ≥ 80 years old (84% vs 91%; p = 0.07). On multivariable analysis, hazard of death increased with refusal overall (HR 1.12, 95% CI 1.04-1.2); but, when stratified by age, was not increased for women ≥ 80 years (HR 1.10, 95% CI 0.80-1.51). CONCLUSIONS: Among healthy women with high-RS, ER-positive BC, chemotherapy refusal was associated with decreased OS for women ages 65-79, but did not impact the OS of women ≥ 80 years old. Genomic testing may have limited utility in this population, warranting prudent shared decision-making and further study.
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Neoplasias de la Mama , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Receptores de Estrógenos/genética , Receptor ErbB-2/genética , Estimación de Kaplan-Meier , Quimioterapia Adyuvante , GenómicaRESUMEN
Cardiovascular disease (CVD) continues as the most important cause of mortality. Better risk screening and prediction are needed to reduce the cardiovascular disease burden. The aim of the study was to assess the role of serum biomarkers in the prediction of CVD among asymptomatic middle-aged adults with no prior CVD history. A systematic review and meta-analysis were carried out using literature from PubMed and following PRISMA reporting guidelines. Twenty-five studies met our inclusion criteria and were included in the systematic review. The most commonly studied biomarker was high-sensitivity C reactive protein (hs-CRP) (10 studies), which showed that higher hs-CRP levels are associated with an increased risk of subsequent CVD events and mortality. In addition, several less-studied biomarkers (N-terminal pro-brain natriuretic peptide (NT-proBNP), fibrinogen, gamma-glutamyl transferase (GGT), and others) also showed significant associations with greater future risk of CVD. A meta-analysis was possible to perform for hs-CRP and NT-proBNP, which showed statistically significant results for the ability of hs-CRP (hazard ratio (HR) 1.19, (95% CI: 1.09−1.30), p < 0.05) and NT-proBNP (HR 1.22, (1.13−1.32), p < 0.05) to predict incident CVD among middle-aged adults without a prior CVD history or symptoms. Several serum biomarkers, particularly hs-CRP and NT-proBNP, have the potential to improve primary CVD risk prevention among asymptomatic middle-aged adults.
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Enfermedades Cardiovasculares , Persona de Mediana Edad , Adulto , Humanos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Proteína C-Reactiva/metabolismo , Factores de Riesgo , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Biomarcadores , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: Occult metastatic tumors, below imaging thresholds, are a limitation of staging systems that rely on cross-sectional imaging alone and are a cause of the routine understaging of pancreatic ductal adenocarcinomas (PDACs). We investigated circulating tumor cells (CTCs) as a preoperative predictor of occult metastatic disease and as a prognostic biomarker for PDAC patients. EXPERIMENTAL DESIGN: A total of 126 patients (100 with cancer, 26 with benign disease) were enrolled in our study and CTCs were identified and enumerated from 4 mL of venous blood using the microfluidic NanoVelcro assay. CTC enumeration was correlated with clinicopathologic variables and outcomes following both surgical and systemic therapies. RESULTS: CTCs were identified in 78% of PDAC patients and CTC counts correlated with increasing stage (ρ = 0.42, p < 0.001). Of the 53 patients taken for potentially curative surgery, 13 (24.5%) had occult metastatic disease intraoperatively. Patients with occult disease had significantly more CTCs than patients with local disease only (median 7 vs. 1 CTC, p < 0.0001). At a cut-off of three or more CTCs/4 mL, CTCs correctly identified patients with occult metastatic disease preoperatively (area under the receiver operating characteristic curve 0.82, 95% confidence interval (CI) 0.76-0.98, p < 0.0001). CTCs were a univariate predictor of recurrence-free survival following surgery [hazard ratio (HR) 2.36, 95% CI 1.17-4.78, p = 0.017], as well as an independent predictor of overall survival on multivariate analysis (HR 1.38, 95% CI 1.01-1.88, p = 0.040). CONCLUSIONS: CTCs show promise as a prognostic biomarker for PDAC patients at all stages of disease being treated both medically and surgically. Furthermore, CTCs demonstrate potential as a preoperative biomarker for identifying patients at high risk of occult metastatic disease.
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Biomarcadores de Tumor/sangre , Carcinoma Ductal Pancreático/secundario , Neoplasias Hepáticas/secundario , Recurrencia Local de Neoplasia/patología , Células Neoplásicas Circulantes/patología , Neoplasias Pancreáticas/patología , Neoplasias Peritoneales/secundario , Anciano , Carcinoma Ductal Pancreático/sangre , Carcinoma Ductal Pancreático/cirugía , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/cirugía , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/cirugía , Pancreatectomía , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/cirugía , Neoplasias Peritoneales/sangre , Neoplasias Peritoneales/cirugía , Pronóstico , Estudios Prospectivos , Tasa de SupervivenciaAsunto(s)
Carcinoma de Células de Merkel , Neoplasias Primarias Desconocidas , Neoplasias Cutáneas , Humanos , Carcinoma de Células de Merkel/patología , Estudios Retrospectivos , Neoplasias Primarias Desconocidas/patología , Neoplasias Cutáneas/patología , Biopsia del Ganglio Linfático Centinela , Ganglios Linfáticos/patología , Escisión del Ganglio LinfáticoRESUMEN
GI cancers are the leading cause of cancer-related death worldwide primarily due to a combination of late presentation and aggressive biology. The lack of adequate biomarkers for screening, diagnosis, staging, and prognosis confounds clinical decision-making and delays potentially effective therapies. Circulating tumor cells (CTCs) are a new biomarker with particular promise in GI cancers, potentially offering clinicians and researchers real-time access to tumor tissue in a reliable, safe, and cost-effective manner. Preliminary studies have investigated the potential clinical utility of CTCs for all GI cancer types with promising results. Furthermore, advances in single cell analytics have been successfully applied to CTCs, allowing for exciting new clinical and research applications. In this chapter, we will review the current state of CTC research in GI cancers as well as the potential future applications that are currently being developed.
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Neoplasias Gastrointestinales/patología , Células Neoplásicas Circulantes , Neoplasias Esofágicas/patología , Humanos , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/patologíaRESUMEN
Lack of a universal site-specific conjugation methodology for antibodies limits their potential to be developed as tumor-specific imaging agents or targeted therapeutics. A potential mechanism for site-specific conjugation involves utilization of the conserved N-glycosylation site in the CH2 domain. We sought to develop an antibody with an altered azido-sugar at this site whereby site-specific label could be added. The HB8059 hybridoma was cultured with peracetylated N-azidoacetlymannosamine (Ac4ManNAz). The resulting azido-sugar antibody was conjugated to phosphine-polyethylene glycol (PEG3)-biotin via a modified Staudinger reaction. Biochemical and functional characterization of the biotinylated antibody was performed. The azido-sugar antibody was also labeled with DyLight-650-Phosphine and injected into mice harboring pancreatic cancer xenografts. The tumors were dissected and imaged utilizing an IVIS fluorescent camera. The antibody was successfully produced in 100 µM Ac4ManNAz. The biotinylated antibody demonstrated a 50 kDa heavy and 25 kDa light chain on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but demonstrated a single band at 50 kDa on western blot. Treatment with a N-linked glycosidase extinguished the band. Flow cytometry demonstrated antigen-specific binding of CA19-9-positive cells and the antibody localized to the antigen-positive tumor in vivo. We successfully produced an antibody with an azido-sugar at the conserved CH2 glycosylation site. We were able to utilize this azide to label the antibody with biotin or fluorescent label and demonstrate that the label is added in a site-specific manner to the heavy chain, N-linked glycosylation site. Finally, we demonstrated functionality of our antibody for in vitro and in vivo targeting of pancreatic cancer cells.
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Anticuerpos Monoclonales de Origen Murino/inmunología , Anticuerpos Antineoplásicos/inmunología , Especificidad de Anticuerpos , Ácido N-Acetilneuramínico/inmunología , Neoplasias Pancreáticas/inmunología , Animales , Línea Celular Tumoral , Femenino , Humanos , Hibridomas , Ratones , Ratones DesnudosRESUMEN
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) patients demonstrate highly variable survival within each stage of the American Joint Committee on Cancer (AJCC) staging system. We hypothesize that tumor grade is partly responsible for this variation. Recently our group developed a novel tumor, node, metastasis, grade (TNMG) classification system utilizing Surveillance Epidemiology and End Results (SEER) data in which the presence of high tumor grade results in advancement to the next higher AJCC stage. This study's objective was to validate this TNMG staging system utilizing single-institution data. METHODS: All patients with PDAC who underwent resection at UCLA between 1990 and 2009 were identified. Clinicopathologic data reviewed included age, sex, node status, tumor size, grade, and stage. Grade was redefined as a dichotomous variable. The impact of grade on survival was assessed by Cox regression analysis. Disease was restaged into the TNMG system and compared to the AJCC staging system. RESULTS: We identified 256 patients who underwent resection for PDAC. Patients with low-grade tumors experienced a 13-month improvement in median survival compared to those with high-grade tumors. On multivariate analysis, tumor grade was the strongest predictor of survival with a hazard ratio of 2.02 (p = 0.0005). Restaging disease according to the novel TNMG staging system resulted in improved survival discrimination between stages compared to the current AJCC system. CONCLUSIONS: We were able to demonstrate that grade is one of the strongest independent prognostic factors in PDAC. Restaging with our novel TNMG system demonstrated improved prognostication. This system offers an effective and convenient way of adding grade to the current AJCC staging system.
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Adenocarcinoma/patología , Carcinoma Ductal Pancreático/patología , Estadificación de Neoplasias/normas , Neoplasias Pancreáticas/patología , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Anciano , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/cirugía , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Clasificación del Tumor , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/cirugía , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Estudios de Validación como AsuntoRESUMEN
Microwave ablation of liver tumors allows preservation of liver parenchyma with good oncologic outcomes. However, ablation of tumors in the caudate lobe is particularly challenging. Adjacent critical anatomy, particularly the biliary hilum, has led to caudate location being considered a relative contraindication to ablation. To date, no series have described laparoscopic microwave ablation of caudate tumors of the liver. We describe our early experience with laparoscopic microwave ablation of caudate tumors. In this retrospective review of a prospectively maintained single-institution database, six patients with six primary or secondary caudate tumors underwent laparoscopic microwave ablation with no complications. At a median follow-up of 10.5 months, five out of six patients are free of caudate recurrence. Laparoscopic microwave ablation of caudate tumors is feasible. Long-term follow-up is needed to determine if local recurrence risk is higher than in other anatomical segments.
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BACKGROUND: American Indian/Alaska Native (AI/AN) breast cancer patients undergo post-mastectomy reconstruction (PMR) infrequently relative to Non-Hispanic White (NHW) patients. Factors associated with low PMR rates among AI/AN are poorly understood. We sought to describe factors associated with this disparity in surgical care. METHODS: A retrospective cohort study of the National Cancer Database (2004 - 2017) identified AI/AN and NHW women, ages 18 - 64, who underwent mastectomy for stage 0 - III breast cancer. Patient characteristics, annual PMR rates, and factors associated with PMR were described with univariable analysis, the Cochran-Armitage test, and multivariable logistical regression. RESULTS: 414,036 NHW and 1,980 AI/AN met inclusion criteria. Relative to NHW, AI/AN had more comorbidities (20% vs 12% Charlson Comorbidity Index ≥ 1, p < 0.001), had non-private insurance (49% vs 20%, p < 0.001), and underwent unilateral mastectomy more frequently (69% vs 61%, p < 0.001). PMR rates increased over the study period, from 13% to 47% for AI/AN and from 29% to 62% for NHW (p <0.001). AI/AN race was independently associated with decreased likelihood of PMR (OR 0.62, 95% CI 0.56-0.69). Among AI/AN, decreased likelihood of PMR was significantly associated with older age at diagnosis, more remote year of diagnosis, advanced disease (tumor size > 5 cm, positive lymph nodes), unilateral mastectomy, non-private insurance, and lower educational attainment in patient's area of residence. CONCLUSION: PMR rates among AI/AN with stage 0 - III breast cancer have increased, yet remain significantly lower than among NHW. Further research should elicit AI/AN perspectives on PMR, and guide early breast cancer detection and treatment.
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Gallbladder cancer is a rare but potentially fatal disease. It is often asymptomatic in early stages and is frequently found incidentally or during the workup for benign biliary disease. We present two patients who each had suspicious gallbladder imaging findings and highlight their differences on radiologic and pathologic examination.
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BACKGROUND: Thermal ablation is an effective treatment for patients with metastatic colon and rectal cancer and allows surgeons to offer curative intent therapy to patients who are otherwise not candidates for resection. We aimed to report outcomes of a single institution experience using microwave ablation (MWA) with or without resection to treat five or more liver metastases. METHODS: In this retrospective cohort study, the University of Minnesota Division of Surgical Oncology liver surgery database was queried to identify all patients who underwent thermal ablation of five or more colorectal liver metastases (CRLM) between 2012-2018. We reviewed patient, disease, and tumor characteristics and measured local, intrahepatic, and extrahepatic recurrence (EHR) rates. We also calculated median overall survival (OS) and disease-free survival (DFS). RESULTS: Ten patients identified had five or more (range, 5-18) tumors ablated with or without combined liver and bowel resection. Median age was 50, and most patients were male (70%) and Caucasian (90%). Four patients received ablation alone (5-12 lesions), while six had combined resection and ablation (5-18 lesions). Ablation was performed laparoscopically in six patients, and four had ablations without resection. All patients received pre- and post-operative chemotherapy. A median of 7 tumors were ablated per patient. Median follow-up was 2.3 years. Among 75 tumors ablated, ablation site recurrence (ASR) (within 1 cm of ablation site) was seen in three with a per-lesion recurrence rate of 4%. Intrahepatic recurrence (IHR) occurred in 6 (60%) patients and EHR in 1 (10%). Five patients underwent retreatment of IHR during follow-up. Median OS was 3 years and DFS was 7.1 months. At the time of last follow up, 6 patients were disease-free. CONCLUSIONS: Thermal ablation can provide acceptable DFS and OS, even with high volume metastatic colorectal cancers. Future efforts should be focused on defining selection criteria for those most likely to benefit from this aggressive approach.
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BACKGROUND: Colorectal liver metastases (CRLM) are the most common extra-lymphatic metastases in colorectal cancers, however, only 15-20% of these patients are candidates for resection. We reviewed our institutional experience with 135 surgical ablations for unresectable CRLM. METHODS: Retrospective review of surgically ablated CRLM from 2009 to 2018. Patient-specific variables were obtained from the medical record. Kaplan-Meier modeling was performed for survival analyses. RESULTS: We ablated 135 CRLM in 36 patients over 40 procedures. Median age was 52 years and 58% of patients were male. All patients received systemic chemotherapy. The ablation procedure was completed laparoscopically in 68% of procedures. Median number of ablated lesions per patient was 2 (range 1-15). Median maximum diameter of ablated lesions was 1.9 cm (range 0.5-12.2). Median follow up of the study was 28 months. In this time, median disease-free survival was not reached. Of the 135 lesions ablated, the per-lesion recurrence rate was 6/135 (4.4%). Median overall survival was 81 months. CONCLUSIONS: Surgical ablation of CRLM can provide excellent local control and long-term survival outcomes in patients who may otherwise not be candidates for other liver-directed therapies.
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Ablación por Catéter/mortalidad , Neoplasias Colorrectales/mortalidad , Hepatectomía/mortalidad , Neoplasias Hepáticas/mortalidad , Microondas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Lymph node-positive biliary tract cancers have poor overall survival. Surgical resection followed by systemic chemotherapy is the mainstay of treatment. We sought to assess the delivery of multimodality therapy in the United States. METHODS: The Surveillance, Epidemiology, and End Results program database was used to identify patients with node-positive biliary tract cancers without distant metastases from 2000 to 2014. Patients were stratified by disease subtype (gallbladder cancer, intrahepatic, extrahepatic, or hilar cholangiocarcinoma) and treatment received (surgery alone, chemotherapy alone, or surgery + chemotherapy). Survival was analyzed using the Kaplan-Meier method and Cox proportional hazard modeling. RESULTS: A total of 3226 patients with node-positive biliary tract cancers were identified. Of 2837 patients who underwent surgical resection, 1386 (49%) received no systemic chemotherapy following surgery, while 1451 (51%) received surgery + chemotherapy. A total of 389 patients (12%) received chemotherapy alone. Median overall survival was longer for patients who underwent surgery + chemotherapy (19 months, p < 0.0001). There was no difference in survival for those who received surgery alone versus chemotherapy alone (10 months for both, p = NS). Receipt of surgery + chemotherapy was independently associated with survival on Cox proportional hazard ratio modeling compared to surgery alone (HR for mortality 1.71, 95% CI 1.56-1.87, p < 0.0001) or chemotherapy alone (HR 1.68, 95% CI 1.46-1.92, p < 0.0001). These trends were consistent across all disease subtypes. DISCUSSION: Optimal survival for node-positive biliary tract cancers depends on multimodality therapy. Following surgery, a substantial proportion of patients do not receive guideline recommended adjuvant therapy.
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Neoplasias del Sistema Biliar/mortalidad , Procedimientos Quirúrgicos del Sistema Biliar/mortalidad , Quimioterapia Adyuvante/mortalidad , Ganglios Linfáticos/patología , Radioterapia Adyuvante/mortalidad , Adolescente , Adulto , Anciano , Neoplasias del Sistema Biliar/patología , Neoplasias del Sistema Biliar/terapia , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Estados Unidos , Adulto JovenRESUMEN
OBJECTIVE: Examine the association between healthy Mediterranean lifestyle practices and cardiovascular disease (CVD) risk factors among New England firefighter recruits. METHODS: A MEDI-Lifestyle score was used to measure adherence to a Mediterranean lifestyle (not smoking, increased physical activity, high adherence to Mediterranean diet, non-obese body mass index, decreased screen time, adequate nightly sleep, and napping) among the recruits. MEDI-Lifestyle scores were cross-sectionally analyzed with blood pressure, aerobic capacity, and other CVD risk factors. RESULTS: Among 92 recruits, high adherence to MEDI-Lifestyle was significantly associated with a decreased risk of prevalent hypertension (odds ratio [OR]â=â0.14 [0.03-0.71]) and a greater probability of high aerobic capacity (ORâ=â5.80 [1.05-32.05]) as compared with low adherence in age- and sex-adjusted analyses. CONCLUSIONS: Increased adherence to MEDI-Lifestyle is associated with a better CVD risk profile in firefighter recruits.
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Bomberos , Estilo de Vida Saludable/fisiología , Hipertensión/prevención & control , Consumo de Oxígeno/fisiología , Adulto , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Hipertensión/epidemiología , Masculino , New England/epidemiología , Oportunidad Relativa , Prevalencia , Conducta de Reducción del Riesgo , Adulto JovenRESUMEN
Melanoma is an aggressive cutaneous malignancy with rapidly rising incidence. Diagnosis of controversial melanocytic lesions, correct prognostication of patients, selection of appropriate adjuvant and systemic therapies, and prediction of response to a given therapy remain very real challenges. Despite these challenges, multiple high throughput, nucleic-acid based biomarkers have been developed that can be assayed from histologic tissue specimens. FISH, CGH, Decision-Dx, and other multi-marker assays have been combined to improve overall predictability. This review discusses some of the most promising nucleic acid based assays that can be obtained from tissue specimens to assist with diagnosis, prognostication, and prediction of treatment response.
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Biomarcadores de Tumor/genética , Melanoma/genética , Pronóstico , Humanos , Melanoma/diagnóstico , Melanoma/patologíaRESUMEN
To understand the potential and limitations of circulating tumor cell (CTC) sequencing for molecular diagnostics, we investigated the feasibility of identifying the ubiquitous KRAS mutation in single CTCs from pancreatic cancer (PC) patients. We used the NanoVelcro/laser capture microdissection CTC platform, combined with whole genome amplification and KRAS Sanger sequencing. We assessed both KRAS codon-12 coverage and the degree that allele dropout during whole genome amplification affected the detection of KRAS mutations from single CTCs. We isolated 385 single cells, 163 from PC cell lines and 222 from the blood of 12 PC patients, and obtained KRAS sequence coverage in 218 of 385 single cells (56.6%). For PC cell lines with known KRAS mutations, single mutations were detected in 67% of homozygous cells but only 37.4% of heterozygous single cells, demonstrating that both coverage and allele dropout are important causes of mutation detection failure from single cells. We could detect KRAS mutations in CTCs from 11 of 12 patients (92%) and 33 of 119 single CTCs sequenced, resulting in a KRAS mutation detection rate of 27.7%. Importantly, KRAS mutations were never found in the 103 white blood cells sequenced. Sequencing of groups of cells containing between 1 and 100 cells determined that at least 10 CTCs are likely required to reliably assess KRAS mutation status from CTCs.