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BACKGROUND: Serum AFP-L3%, AFP, and DCP are useful biomarkers for HCC detection, but their utility in assessing treatment response remains unknown. We aim to evaluate the accuracy of a biomarker model in the detection of posttreatment viable tumors. METHODS: For model derivation, recipients with HCC undergoing liver transplant from 2018 to 2022 who had biomarkers collected within 3 months before transplant were included. We developed a generalized linear model for detecting posttreatment viable tumors with the 3 biomarkers as covariates, which we termed the "LAD Score." An independent cohort of 117 patients with HCC was used for external validation. RESULTS: Among 205 recipients of transplant, 70.2% had evidence of viable tumor on explant. The median LAD score was higher among patients with viable versus nonviable tumors (1.06 vs. 0.465, p < 0.001). The LAD score had a sensitivity of 55.6% and a specificity of 85.1% at the cutoff of 0.927, which was more accurate than imaging for detecting posttreatment viable tumors (AUROC 0.736 vs. 0.643, respectively; p = 0.045). The superior performance of the LAD score over imaging is primarily driven by its greater accuracy in detecting tumors <2 cm in diameter (AUROC of the LAD score 0.721 vs. imaging 0.595, p = 0.02). In the validation data set, the LAD score had an AUROC of 0.832 (95% CI: 0.753, 0.911) with a sensitivity of 72.5% and a specificity of 89.4% at the cutoff of 0.927. CONCLUSIONS: Our findings suggest the utility of LAD score in treatment response assessment after locoregional therapy for HCC, particularly in detecting small tumors. A larger prospective study is in progress to validate its accuracy and evaluate its performance in recurrence monitoring.
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Biomarcadores Tumorais , Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , alfa-Fetoproteínas , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , alfa-Fetoproteínas/análise , Idoso , Resultado do Tratamento , Sensibilidade e Especificidade , Estudos RetrospectivosAssuntos
Carcinoma Ductal Pancreático , Regulador de Condutância Transmembrana em Fibrose Cística , Predisposição Genética para Doença , Testes Genéticos , Mutação em Linhagem Germinativa , Neoplasias Pancreáticas , Humanos , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Neoplasias Pancreáticas/genética , Testes Genéticos/métodos , Carcinoma Ductal Pancreático/genética , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fenótipo , Valor Preditivo dos Testes , Biomarcadores Tumorais/genética , Adulto , Análise Mutacional de DNARESUMO
INTRODUCTION: The efficacy and safety of combined immunotherapy and transarterial radioembolization (TARE) were suggested in preclinical and early-phase trials, but these were limited by small sample sizes. We sought to compare the efficacy of combined therapy and immunotherapy alone in patients with advanced hepatocellular carcinoma (HCC). METHODS: The National Cancer Database was used to identify patients with advanced HCC diagnosed between January 1, 2017, and December 31, 2019. We included patients who received combined therapy or immunotherapy alone as first-line treatment. Multivariable logistic regression was conducted to determine predictors of combined therapy. Kaplan-Meier and Cox regression approaches were used to identify predictors of overall survival and to compare hazards of mortality between the patients who received combined therapy and immunotherapy alone. RESULTS: Of 1,664 eligible patients with advanced-stage HCC, 142 received combined TARE/immunotherapy and 1,522 received immunotherapy alone. Receipt of combination therapy was associated with care at an academic center and inversely associated with racial/ethnic minority status (Hispanic and Black individuals). The median overall survival was significantly higher in the combination group than in the immunotherapy alone group (19.8 vs 9.5 months). In multivariable analysis, combined therapy was independently associated with reduced mortality (adjusted hazard ratio 0.50, 95% confidence interval: 0.36-0.68, P < 0.001). Results were consistent across subgroups and in sensitivity analyses using propensity score matching and inverse probability of treatment weighting. DISCUSSION: The combination of TARE and immunotherapy was associated with improved survival compared with immunotherapy alone in patients with advanced-stage HCC. Our findings underly the importance of large clinical trials evaluating combination therapy in these patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Etnicidade , Estudos Retrospectivos , Grupos Minoritários , Imunoterapia , Resultado do TratamentoRESUMO
BACKGROUND: Complementary feeding practices may contribute to toddler eating practices that affect weight outcomes. Studies are needed to understand the relationship between complementary feeding practices and toddler dietary self-regulation. OBJECTIVE: This study tests the hypothesis that earlier complementary food introduction predicts toddler food responsiveness and emotional overeating (ie, tendency to overeat in response to food cues and emotions, respectively), and considers whether introduction of certain foods better predict toddler dietary self-regulation. DESIGN: This study is a secondary analysis of data from a parent longitudinal birth cohort study on early growth/development among Hispanic mother-infant dyads. PARTICIPANTS/SETTING: The analytic sample included 174 mother-child dyads recruited from maternity clinics affiliated with the University of Southern California in Los Angeles County. Recruitment and data collection were ongoing from July 2016 to April 2020. At 1-, 6-, 12-, and 24-months postpartum, mothers reported exclusive breastfeeding duration and age of complementary food introduction via questionnaire. MAIN OUTCOME MEASURES: Child food responsiveness and emotional overeating scores calculated from the Child Eating Behavior Questionnaire at 12 and 24 months of age. STATISTICAL ANALYSES PERFORMED: Separate linear mixed models with repeated measures were used to examine associations between age of complementary food introduction as a predictor of child food responsiveness or emotional overeating, controlling for infant sex, birth body mass index z score, duration of exclusive breastfeeding, and mother's body mass index. RESULTS: In separate models, delaying complementary food introduction by 1 month was associated with a 6% reduction in food responsiveness (P = 0.007) and a 5% reduction in emotional overeating scores (P = 0.013). Fifty-eight unique combinations of complementary foods introduced first were found, precluding analyses to examine whether specific combinations were related to eating behavior outcomes due to sample size limitations. CONCLUSIONS: Earlier complementary feeding was associated with higher food responsiveness and emotional overeating scores among Hispanic children. Future studies in larger samples are needed to characterize patterns of complementary food introduction and their influence on child self-regulation.
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Comportamento Apetitivo , Comportamento Alimentar , Hiperfagia , Fenômenos Fisiológicos da Nutrição do Lactente , Feminino , Humanos , Lactente , Gravidez , Índice de Massa Corporal , Aleitamento Materno , Estudos de Coortes , Comportamento Alimentar/psicologia , Hispânico ou Latino , Relações Mãe-Filho , Inquéritos e QuestionáriosRESUMO
BACKGROUND & AIMS: In 2021, the US Preventive Services Task Force lowered the colorectal cancer (CRC) screening age to 45 years. We used conjoint analysis, a method that assesses complex decision making, to update our understanding on people's CRC screening test preferences in the context of new guidelines. METHODS: We conducted a conjoint analysis survey among unscreened individuals ≥40 years at average risk for CRC to determine the relative importance of screening test attributes in their decision making (eg, modality, effectiveness at reducing CRC risk, bowel prep). We also performed simulations to estimate the proportion of people who would prefer each US Multi-Society Task Force (MSTF) on CRC-recommended test. The analyses were stratified among those aged 40-49 years (newly or soon-to-be eligible for screening) and ≥50 years (have been eligible). RESULTS: Overall, 1000 participants completed the conjoint analysis (40-49 years, n = 456; ≥50 years, n = 544). When considering all 5 US MSTF-recommended tests, there were differences in test preferences between age groups (P = .019), and the most preferred test was a fecal immunochemical test (FIT)-fecal DNA every 3 years: 40-49 years, 34.6%; ≥50 years, 37.3%. When considering only the US MSTF tier 1 tests, most 40- to 49- (68.9%) and ≥50-year-olds (77.4%; P = .004) preferred an annual FIT over a colonoscopy every 10 years. CONCLUSIONS: Our findings suggest that more than one-third of people may want to do a FIT-fecal DNA every 3 years for their CRC screening. When only considering US MSTF tier 1 tests, three-fourths of people may prefer an annual FIT over colonoscopy. Further research examining CRC screening test preferences among broader populations is warranted to inform and enhance screening programs.
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Neoplasias Colorretais , Preferência do Paciente , Humanos , Detecção Precoce de Câncer/métodos , Colonoscopia , DNA/análise , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Sangue Oculto , Programas de Rastreamento/métodosRESUMO
BACKGROUND: Curative surgical treatments afford the best prognosis for patients with intrahepatic cholangiocarcinoma (iCCA); however, the comparative effectiveness of treatment options and factors associated with curative treatment receipt for early stage iCCA remain unknown. METHODS: The authors identified patients who were diagnosed with early stage iCCA, defined as a unifocal tumor <3 cm, during 2004-2018 from the National Cancer Database. Multivariable logistic and Cox regression analyses were used to identify the factors associated with curative treatment and overall survival (OS), respectively. RESULTS: The proportion of patients with early stage iCCA increased from 4.5% in 2004 to 7.3% in 2018, with the odds of early stage detection increasing by 3.1% per year (odds ratio [OR], 1.031; 95% CI, 1.015-1.049). Of 1093 patients who had early stage iCCA, 464 (42.5%) underwent resection, 113 (10.3%) underwent ablation, 62 (5.7%) underwent liver transplantation, and 454 (41.5%) received noncurative treatments. Hispanic patients (adjusted OR [aOR], 0.57; 95% CI, 0.33-0.97) and Black patients (aOR, 0.47; 95% CI, 0.28-0.77) were less likely to receive curative treatments than White patients. Compared with patients who underwent surgical resection, those who underwent liver transplantation had a trend toward improved OS (adjusted hazard ratio [aHR], 0.63; 95% CI, 0.37-1.08), whereas those who underwent local ablation (aHR, 1.39; 95% CI, 1.01-1.92) and noncurative treatments (aHR, 3.97; 95% CI, 3.24-4.88) experienced worse OS. CONCLUSIONS: More than one third of patients with early stage iCCA did not receive curative treatment, with Hispanic and Black patients being less likely to receive curative treatments than White patients. Surgical resection and liver transplantation were associated with improved survival compared with local ablation. Future studies should investigate disparities in curative treatment receipt and outcomes for early stage iCCA.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/cirurgia , Detecção Precoce de Câncer , Humanos , Prognóstico , Estados Unidos/epidemiologiaRESUMO
Although many people prefer fecal immunochemical test (FIT) over colonoscopy due to its noninvasive nature, it is unclear whether FIT would still be preferred for colorectal cancer (CRC) screening if they were explicitly informed that + FIT requires follow-up colonoscopy. To address this gap, we administered two conjoint analysis surveys-one that explained the need for a follow-up colonoscopy after + FIT while the other did not-to a US nationwide sample of Americans and then assessed whether there were differences in colonoscopy/FIT preferences between cohorts. We recruited adults ≥ 40yo who had not undergone CRC screening via an online survey research firm. We deployed two surveys that used conjoint analysis to assess decision making surrounding CRC screening tests: Survey 1 (4/2-4/15/2021)-did not inform participants that they need a colonoscopy following a + FIT; Survey 2 (4/29-6/2/2021)-informed respondents of the potential need. Using the conjoint analysis data, we determined the proportion of those who preferred FIT or colonoscopy and then used logistic regression to assess for differences in colonoscopy/FIT preferences between the cohorts. Overall, 501 and 1,000 individuals completed Survey 1 (without description of need for colonoscopy after + FIT) and Survey 2 (with description), respectively. There was no difference in test preference between cohorts after adjusting for covariates in the logistic regression (adjusted p = 0.09): Survey 1 (without description)-colonoscopy 28.5%, FIT 71.5%; Survey 2 (with description)-colonoscopy 26.7%, FIT 73.3%. Thus, knowledge that a + FIT requires a follow-up colonoscopy does not alter people's strong preference for non-invasive stool testing with FIT.
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BACKGROUND AND AIMS: Immunotherapy has emerged as an effective treatment for patients with advanced-stage HCC. We aimed to investigate the efficacy of immunotherapy for advanced HCC in a nationwide cohort and racial and ethnic disparities in access to immunotherapy. APPROACH AND RESULTS: We used the US National Cancer Database to identify patients with tumor-node-metastasis stage 3 or 4 HCC between 2017 and 2018. We performed multivariable Cox regression to identify factors associated with overall survival (OS) and logistic regression to identify factors associated with receipt of immunotherapy. Of the 3,990 patients treated for advanced HCC, 3,248 (81.4%) patients received chemotherapy and 742 (18.6%) patients received immunotherapy as a first-line treatment. Immunotherapy was associated with improved OS compared with chemotherapy (adjusted HR: 0.76, 95% CI: 0.65-0.88) after adjusting for covariates. There were racial and ethnic disparities in access to immunotherapy, with Hispanic (adjusted OR [aOR]: 0.63, 95% CI: 0.46-0.83) and Black patients (aOR: 0.71, 95% CI: 0.54-0.89) less likely to receive immunotherapy compared with White patients. There was a significant interaction between race-ethnicity and facility type, with higher disparity observed in nonacademic centers (interaction p = 0.004). CONCLUSIONS: Immunotherapy was associated with improved OS compared with chemotherapy in advanced HCC. There are significant disparities in early access to immunotherapy, likely due to differential access to clinical trials and experimental therapies. A comprehensive approach to monitoring and eliminating racial-ethnic disparities in the management of advanced HCC is urgently needed.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Estados Unidos , Humanos , Etnicidade , Carcinoma Hepatocelular/patologia , Disparidades em Assistência à Saúde , Neoplasias Hepáticas/patologia , ImunoterapiaRESUMO
The COVID-19 pandemic has the potential to impact long-standing efforts to increase adherence to cancer screening guidelines. Healthcare workers (HCWs) experienced significant hardship, but generally have greater access to preventive services, making them a particularly relevant population in which to understand cancer screening behaviors during the pandemic. We report data from 794 HCWs enrolled in the NCI-funded Serological Sciences Network for Coronavirus Associations and Longitudinal Evaluation Study from December 2020 to April 2021. Participants reported lifestyle and screening behaviors during relevant look-back periods which included the pandemic timeframe. Among women between the ages of 40 and 74, 25.7% were overdue for mammographic breast cancer screening. Among participants 50-75 years old, 38.9% were overdue for colorectal cancer screening. The proportion over-due varied according to race/ethnicity. Lifetime low-dose computed tomography lung cancer screening among HCWs age 50-80 years who were smokers was 10.9%. Strategies to address screening disruptions are needed to minimize the impact of later stage of diagnosis.
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COVID-19 , Neoplasias Pulmonares , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , COVID-19/epidemiologia , Detecção Precoce de Câncer , Feminino , Pessoal de Saúde , Humanos , Pessoa de Meia-Idade , PandemiasRESUMO
INTRODUCTION: While providers generally counsel patients about possible effects of gender affirming treatments, such as gender affirming hormone therapy (GAHT) and gender affirming surgery (GAS), on sexual function - the effects of these treatments on orgasm function and quality are not well understood. AIM: To develop a gender transition orgasm quality inventory based on orgasm function domains transgender patients communicated were important to them. METHODS: We conducted a series of interviews in which we asked transgender patients to describe which factors related to orgasm (ie, orgasm quality and orgasm-related sexual function) were most important to them. This work generated a list of 6 domains which we incorporated into a survey instrument. The 6 domains that our work generated are: (1) Lead-time to reach orgasm, (2) Duration of orgasm, (3) Body location of orgasm sensation; (4) Description of orgasm as either a single or multiple-peak event, (5) Duration of postorgasm refractory period, and (6) Overall satisfaction with orgasm quality. Using this new questionnaire, we queried potential changes in orgasm function before and after commencing GAHT (minimum 1 year) among 130 consecutive transgender women (TW) and 33 transgender men (TM) as a pilot study. RESULTS: Within groups by gender, TW and TM cohorts reported similar responses to our inventory before starting GAHT. After commencing GAHT, TW reported notable changes in orgasm function: increase in lead-time necessary to reach orgasm, orgasm duration, and overall orgasm satisfaction; and decrease in post-orgasm refractory period. Similarly, TM reported an increase in duration of orgasm and increased overall satisfaction with orgasm quality; and a decrease in post-orgasm refractory period. Over half of the TW reported experiencing orgasms in new/additional body locations. Additionally, prior to commencing GAHT, the majority of TM and TW patients reported their orgasms as a short, single-peak event but following GAHT these same patients reported longer and protracted multiple-peak orgasms. CONCLUSION: We have developed a novel questionnaire with the purpose of assessing patient self-reported changes in orgasm function following gender affirming treatments. Findings from our pilot study shows that GAHT has the potential to positively improve sexual function and orgasm quality for transgender patients undergoing gender transition. We encourage future studies to utilize our novel questionnaire to assess potential changes in orgasm function related to various gender affirming procedures. Zaliznyak M, Lauzon M, Stelmar J, et al. A Proposed Inventory to Assess Changes in Orgasm Function of Transgender Patients Following Gender Affirming Treatments: Pilot Study. Sex Med 2022;10:100510.
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BACKGROUND: Previous studies have demonstrated positive impacts of advance care planning (ACP) on end-of-life (EOL) care. We sought to examine trends in ACP and EOL care intensity among persons living with dementia who required surrogate decision-making in their final days of life. METHODS: We analyzed the participants of the Health and Retirement Study (HRS), a nationally representative longitudinal panel study of U.S. residents, with dementia 70 years and older who required surrogate decision-making in the final days of life and died between 2000 and 2014. Based on surrogate reports after the death of a participant, our study measured the completion of three specific types of patient-engaged ACP (written EOL care instructions, assignment of a durable power of attorney for healthcare, patient engagement in EOL care discussions) and four measures of EOL care in the final days of life (death in hospital, receipt of life-prolonging treatments, limiting or withholding certain treatments, and receipt of comfort-oriented care). All analyses accounted for the complex survey design of HRS. RESULTS: Among 870 adults (weighted N = 2,812,380) with dementia who died in 2000-2014 and required surrogate decision-making at EOL, only 34.8% of patients participated in all three aspects of ACP, and there was not a significant increase in ACP completion between 2000 and 2014. The receipt of life-prolonging treatments in the final days of life has increased over time (adjusted change per year, 1.4 percentage points [pp]; 95% CI, 0.5 to 2.2 pp; P-for-trend = 0.002), while the percentage of death in hospital, limiting or withholding certain treatments, or comfort-oriented care did not change. CONCLUSIONS: Our findings suggest that the rates of ACP completion have not increased over time despite its potential benefits and life-prolonging treatments are still common among PLWD who require surrogate decision-making, a population who might benefit greatly from early ACP.
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Planejamento Antecipado de Cuidados , Demência , Assistência Terminal , Demência/terapia , Humanos , Cuidados Paliativos , Participação do PacienteRESUMO
BACKGROUND: While advanced care planning (ACP) is recommended in dementia and cancer care, there are unique challenges in ACP for individuals with dementia, such as the insidious onset and progression of cognitive impairment, potentially leading to high-intensity care at the end of life (EOL) for this population. OBJECTIVE: To compare ACP completion and receipt of high-intensity care at the EOL between decedents with dementia versus cancer. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: Participants of the U.S. Health and Retirement Study who died between 2000 and 2014 with dementia (n = 2099) and cancer (n = 1137). MAIN MEASURES: Completion of three types of ACP (living will, durable power of attorney for healthcare [DPOAH], discussions of preferences for EOL care) and three measures of EOL care intensity (in-hospital death, intensive care unit [ICU] care in the last 2 years of life, life support use in the last 2 years of life). KEY RESULTS: Use of living will was lower in dementia than in cancer (adjusted proportion, 49.9% vs. 56.9%; difference, - 7.0 percentage points [pp, 95% CI, - 13.3 to - 0.7]; p = 0.03). Use of DPOAH was similar between the two groups, but a lower proportion of decedents with dementia had discussed preferences compared to decedents with cancer (53.0% vs. 68.1%; - 15.1 pp [95% CI, - 19.3 to - 10.9]; p < 0.001). In-hospital death was higher in dementia than in cancer (29.5% vs. 19.8%; + 9.7 pp [95% CI, + 5.9 to + 13.5]; p < 0.001), although use of ICU care was lower (20.9% vs. 26.1%; - 5.2 pp [95% CI, - 9.8 to - 0.7]; p = 0.03). Use of life support was similar between the two groups. CONCLUSIONS: Individuals with dementia complete ACP less frequently and might be receiving higher-intensity EOL care than those with cancer. Interventions targeting individuals with dementia may be necessary to further improve EOL care for this population.
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Planejamento Antecipado de Cuidados , Demência , Neoplasias , Assistência Terminal , Demência/epidemiologia , Demência/terapia , Mortalidade Hospitalar , Humanos , Estudos Longitudinais , Neoplasias/epidemiologia , Neoplasias/psicologia , Neoplasias/terapia , Estudos Retrospectivos , Assistência Terminal/psicologiaRESUMO
Prognosis of hepatocellular carcinoma (HCC) could be affected by lack of or delayed therapy. We aimed to characterize the prevalence, correlates, and clinical impact of therapeutic underuse and delay in patients with HCC. Patients with HCC diagnosed between 2010 and 2017 were analyzed from the United States National Cancer Database. Logistic regression analysis identified factors associated with no and delayed (>90 days after diagnosis) HCC treatment. Cox proportional hazards regression with landmark analysis assessed the association between therapeutic delay and overall survival (OS), accounting for immortal time bias. Of 116,299 patients with HCC, 24.2% received no treatment and 18.4% of treated patients had delayed treatment. Older age, Black, Hispanic, lower socioeconomic status, earlier year of diagnosis, treatment at nonacademic centers, Northeast region, increased medical comorbidity, worse liver dysfunction, and higher tumor burden were associated with no treatment. Among treated patients, younger age, Hispanic, Black, treatment at academic centers, West region, earlier tumor stage, and receipt of noncurative treatment were associated with treatment delays. In multivariable Cox regression with a landmark of 150 days, patients with and without treatment delays had similar OS (adjusted hazard ratio [aHR], 1.01; 95% confidence interval [CI], 0.98-1.04) with a median survival of 33.7 vs. 32.1 months, respectively. However, therapeutic delay was associated with worse OS in patients who had tumor, nodes, and metastases (TNM) stage 1 (aHR, 1.06; 95% CI, 1.01-1.11) or received curative treatment (aHR, 1.12; 95% CI, 1.05-1.18). Conclusion: One-fourth of patients with HCC receive no therapy and one-fifth of treated patients experience treatment delays. Both were associated with demographic, socioeconomic, and clinical characteristics of patients as well as facility type and region. The association between therapeutic delay and survival was stage and treatment dependent.
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Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Tempo para o Tratamento , Idade de Início , Idoso , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etnologia , Carcinoma Hepatocelular/mortalidade , Feminino , Disparidades em Assistência à Saúde , Humanos , Cobertura do Seguro , Seguro Saúde , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etnologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Classe Social , Carga Tumoral , Estados Unidos/epidemiologiaRESUMO
Serum α-fetoprotein (AFP), a well-established biomarker for hepatocellular carcinoma (HCC), increases the sensitivity of ultrasound-based surveillance programs for early stage HCC detection.1,2 Multiple factors, including tumor burden, can affect AFP levels in patients with HCC.3 Nontumoral factors, such as race/ethnicity and liver disease etiology, are also known to be associated with elevated AFP.3 With the increasing trend of earlier stage HCC detection and shift from viral to nonviral etiology, we hypothesized that AFP level at HCC diagnosis would decrease in the United States.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais , Carcinoma Hepatocelular/patologia , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/patologia , Estados Unidos , alfa-FetoproteínasRESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with poor survival. The dense desmoplastic stroma in PDAC contributes to treatment resistance. Among the components comprising the tumor stroma, hyaluronan (HA) has been demonstrated to play a critical role in tumor progression and survival. Previous preliminary studies have suggested differences in HA expression in primary and metastatic foci of PDAC. However, the effects of treatment and location of HA expression as a biomarker signature remain unknown; this study sought to compare HA expression in primary and metastatic sites of PDAC. METHODS: Tissue from primary and metastatic PDACs were obtained from Cedars-Sinai Medical Center along with associated clinical data. Tissue slides were stained for H&E, HA, and CD44. Associations between HA levels and the evaluated variables were examined including progression free survival and overall survival. RESULTS: HA score was significantly higher in primary PDACs compared to sites of metastases (p = 0.0148). Within the metastases, HA score was significantly higher in liver metastases compared to metastases at other sites (p = 0.0478). In the treatment-naive liver metastasis cohort, patients with HA high status had decreased progression free survival and overall survival compared to patients with HA low status (p = 0.0032 and p = 0.0478, respectively). CONCLUSIONS: HA score is variable between primary PDAC, PDAC metastatic to the liver, and PDAC metastatic to other sites. Within liver metastases, patients with HA high status had decreased progression free survival and overall survival compared to patients with HA low status. HA levels can serve as a potential biomarker to guide pancreatic cancer treatments and trial design for agents targeting the stroma.
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Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/diagnóstico , Ácido Hialurônico/metabolismo , Neoplasias Pancreáticas/diagnóstico , Adjuvantes Imunológicos , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Humanos , Neoplasias Hepáticas , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Neoplasias PancreáticasRESUMO
INTRODUCTION: Small studies from outside of the USA suggest excellent outcomes after surgical resection for hepatocellular carcinoma (HCC) with vascular invasion. The study aims to (1) compare overall survival after surgical resection and systemic therapy among patients with HCC and vascular invasion and (2) determine factors associated with receipt of surgical resection in a US population. METHODS: HCC patients with AJCC clinical TNM stage 7th T3BN0M0 diagnosed between 2010 and 2017 from the National Cancer Database were analyzed. Cox and logistic regression analyses identified factors associated with overall survival and receipt of surgical resection. RESULTS: Of 11,259 patients with T3BN0M0 HCC, 325 (2.9%) and 4,268 (37.9%) received surgical resection and systemic therapy, respectively. In multivariable analysis, surgical resection was associated with improved survival compared to systemic therapy (adjusted hazard ratio: 0.496, 95% confidence interval: 0.426-0.578) with a median survival of 21.4 and 8.1 months, respectively. Superiority of surgical resection was observed in noncirrhotic and cirrhotic subgroups and propensity score matching and inverse probability of treatment weighting adjusted analysis. Asians were more likely to receive surgical resection, whereas Charlson comorbidity ≥3, elevated alpha-fetoprotein, smaller tumor size, care in a community cancer program, and the South or West region were associated with a lower likelihood of surgical resection. CONCLUSION: HCC patients with vascular invasion may benefit from surgical resection compared to systemic therapies. Demographic and clinical features of HCC patients and region and type of treating facility were associated with surgical resection versus systemic treatment.
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BACKGROUND: Advanced pancreatic ductal adenocarcinoma (PDAC) is characterized by progressive weight loss and nutritional deterioration. This wasting has been linked to poor survival outcomes, alterations in host defenses, decreased functional ability, and diminished health-related quality of life (HRQOL) in pancreatic cancer patients. There are currently no standardized approaches to the management of pancreatic cancer cachexia. This study explores the feasibility and efficacy of enteral tube feeding of a peptide-based formula to improve weight stability and patient-reported outcomes (PROs) in advanced PDAC patients with cachexia. METHODS: This was a single-institution, single-arm prospective trial conducted between April 2015 and March 2019. Eligible patients were adults (>18 years) diagnosed with advanced or locally advanced PDAC and cachexia, defined as greater than 5% unexplained weight loss within 6 months from screening. The study intervention included three 28 day cycles of a semi-elemental peptide-based formula, administered through a jejunal or gastrojejunal feeding tube. The primary outcome was weight stability at 3 months (Cycle 3), defined as weight change less than 0.1 kg/baseline BMI unit from baseline. Secondary outcomes included changes in lean body mass, appendicular lean mass, bone mineral density, fat mass, and percent body fat, as measured with a DEXA scan, HRQOL (EORTC QLQC30) and NIH PROMIS PROs assessed at each cycle. Daily activity (steps, distance, active minutes, heart rate, and sleep) were remotely monitored using a wearable activity monitor (Fitbit) over the 3 month study period. RESULTS: Thirty-six patients were screened for eligibility, 31 patients consented onto study and underwent jejunal tube placement, and 16 patients completed treatment: mean age 67 years (SD 9.3), 43.8% male. Among evaluable patients (n = 16), weight stability was achieved in 10 patients (62.5%), thus completing the trial early. Increases in lean body mass (1273.1, SD: 4078, P = 0.01) and appendicular lean mass (0.45, SD: 0.6, P = 0.02) were observed. Statistically significant improvements at Cycle 3 from baseline were also observed for QLQC30 role function [mean difference (MD): 20.1, P = 0.03], appetite (MD: 27.4, P = 0.02), and global health scores (MD: 13.3, P = 0.05) as well as for NIH PROMIS t-scores for depression (MD: -10.4, P = 0.006) and pain interference (MD: -7.5, P = 0.05). Objectively monitored (Fitbit) activity levels increased, although statistical significance was not reached. CONCLUSIONS: Our findings suggest that enteral nutrition support may improve weight stability, lean body mass, appendicular lean mass and PROs in PDAC patients with cachexia who completed treatment, representing a subsample of the study population. The feasibility and role of enteral feeding in routine care remain unclear, and larger and randomized controlled trials are warranted.
Assuntos
Caquexia , Nutrição Enteral , Neoplasias Pancreáticas , Idoso , Caquexia/etiologia , Caquexia/terapia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/terapia , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Qualidade de VidaRESUMO
Background and Aims: Systemic therapy remains the recommended first-line treatment for hepatocellular carcinoma (HCC) with macrovascular invasion (MVI). Transarterial radioembolization (TARE) is a promising alternative treatment given superior quality of life. The aims of this study were to 1) characterize trends and correlates for TARE as first-line treatment of HCC patients with MVI in the US and 2) compare survival after TARE versus systemic therapy. Methods: We used the US National Cancer Database to identify patients with T3BN0M0 HCC during 2010-2017. We performed multivariable logistic regression to identify factors associated with use of TARE vs. systemic therapy and Cox proportional hazards regression to identify factors associated with overall survival. Results: Of 11,259 patients with T3BN0M0 HCC, 1454 (12.9%) and 3915 (34.7%) patients were treated with TARE and systemic therapy, respectively. The proportion of patients who received TARE increased from 13.0% in 2010 to 37.0% in 2017. Older age, White race, and receiving care at an academic cancer program were associated with receipt of TARE, while lack of insurance, higher MELD score, Charlson comorbidity Index ≥3, and Northeast region were associated with receipt of systemic therapy. TARE was associated with reduced mortality compared to systemic therapy (adjusted hazard ratio: 0.74, 95%CI: 0.68-0.80), with consistent results observed in propensity weighted analysis and across all examined subgroups. Conclusion: Use of TARE as first-line therapy for HCC with MVI has increased in the US. Patient characteristics, region, and medical center type affected the use of TARE. TARE was associated with reduced mortality compared to systemic therapy for HCC patients with MVI.
RESUMO
BACKGROUND: An easy-to-operate ECG recorder should be useful for newborn screening for heart conditions, by health care workers - or parents. We developed a one-piece electrode strip and a compact, 12lead ECG recorder for newborns. METHOD: We enrolled 2582 newborns in a trial to assess abilities of parents to record a 12lead ECG on their infants (2-4â¯weeks-old). Newborns were randomized to recordings by parents (1290) or our staff (1292 controls). Educational backgrounds of parents varied, including 64% with no more than a high school diploma. RESULTS: For newborns randomized to parent recorded ECGs, 94% of parents completed a 10-minute recording. However, 42.6% asked for verbal help, and 12.7% needed physical help. ECG quality was the same for recordings by parents versus staff. CONCLUSIONS: By use of a one-piece electrode strip and a compact recorder, 87% of parents recorded diagnostic quality ECGs on their newborn infants, with minimal assistance.