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BACKGROUND AND AIMS: Emerging data suggest neoadjuvant chemotherapy (NAC) for resectable pancreatic ductal adenocarcinoma (PDAC) is associated with improved survival. However, less than 40% of patients demonstrate a meaningful radiographic response to NAC. EUS-guided radiofrequency ablation (EUS-RFA) has emerged as a new modality to treat PDAC. We hypothesize that NAC plus EUS-RFA can be used in the management of resectable PDAC. METHODS: This was a prospective review of PDAC patients meeting the criteria of resectable tumor anatomy who underwent NAC chemotherapy plus EUS-RFA followed by pancreatic resection. Radiographic imaging and perioperative and short-term outcomes were recorded. Surgical pathology specimens were analyzed for treatment response. RESULTS: Three eligible patients with resectable PDAC received 4 months of NAC plus EUS-RFA. One month after completing NAC and EUS-RFA, all 3 patients underwent standard pancreaticoduodenectomy without adverse events. After a 6-week recovery, all patients completed 2 months of postoperative adjuvant chemotherapy. CONCLUSIONS: In our institutional experience, this treatment protocol appears to be safe as patients tolerated the combination of chemotherapy and ablation. Patients underwent pancreatic resection with uneventful recovery. This novel neoadjuvant approach may provide a more effective alternative to chemotherapy alone.
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Carcinoma Ductal Pancreático , Endossonografia , Terapia Neoadjuvante , Neoplasias Pancreáticas , Ablação por Radiofrequência , Humanos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Ablação por Radiofrequência/métodos , Masculino , Pessoa de Meia-Idade , Idoso , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/terapia , Estudos Prospectivos , Feminino , Quimioterapia Adjuvante , Pancreaticoduodenectomia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ultrassonografia de Intervenção , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Adenocarcinoma/cirurgia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Oxaliplatina/administração & dosagemRESUMO
This clinical practice guideline from the American Society for Gastrointestinal Endoscopy provides an evidence-based approach for the diagnosis of malignancy in patients with biliary strictures of undetermined etiology. This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework and addresses the role of fluoroscopic-guided biopsy sampling, brush cytology, cholangioscopy, and EUS in the diagnosis of malignancy in patients with biliary strictures. In the endoscopic workup of these patients, we suggest the use of fluoroscopic-guided biopsy sampling in addition to brush cytology over brush cytology alone, especially for hilar strictures. We suggest the use of cholangioscopic and EUS-guided biopsy sampling especially for patients who undergo nondiagnostic sampling, cholangioscopic biopsy sampling for nondistal strictures and EUS-guided biopsy sampling distal strictures or those with suspected spread to surrounding lymph nodes and other structures.
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Biliary strictures of undetermined etiology pose a diagnostic challenge for endoscopists. Despite advances in technology, diagnosing malignancy in biliary strictures often requires multiple procedures. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to rigorously review and synthesize the available literature on strategies used to diagnose undetermined biliary strictures. Using a systematic review and meta-analysis of each diagnostic modality, including fluoroscopic-guided biopsy sampling, brush cytology, cholangioscopy, and EUS-guided FNA or fine-needle biopsy sampling, the American Society for Gastrointestinal Endoscopy Standards of Practice Committee provides this guideline on modalities used to diagnose biliary strictures of undetermined etiology. This document summarizes the methods used in the GRADE analysis to make recommendations, whereas the accompanying article subtitled "Summary and Recommendations" contains a concise summary of our findings and final recommendations.
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INTRODUCTION: In response to the COVID-19 pandemic, hospitals reported decreased admissions for acute surgical diagnoses, but scant data was available to quantify the decrease and its consequences. The objective of this study was to examine the incidence of acute care surgery encounters before and during the COVID-19 pandemic. MATERIALS AND METHODS: A retrospective cohort study was performed at a single, urban, United States safety-net hospital. Emergency room encounters, admissions, non-elective surgical procedures, patient acuity, and surgical complications were compared before and after the start of the COVID-19 pandemic. The primary outcome of the study was the incidence rate (IR) and incidence rate ratios (IRR) for surgical admissions, laparoscopic appendectomy, and urgent laparoscopic cholecystectomy. RESULTS: During the COVID-19 (exposure) time period, the number of nonelective procedures was 143 (IR 4.76) which was significantly lower than the control periods (n = 431, IR 7.2), P < 0.001. During the COVID-19 exposure period, there were significantly fewer urgent cholecystectomies performed (1.37 per day versus 2.80-2.93 per day, P < 0.001). There was a trend toward fewer appendectomies performed, but not significant. There was little difference in patient acuity between the exposure and control periods. A higher proportion of patients that underwent urgent cholecystectomy during the COVID time period had been seen in the ED in the prior 30 d (22% versus 5.6%). CONCLUSIONS: Surgical volume significantly decreased during the COVID-19 pandemic. Management of acute cholecystitis may require re-evaluation as nonsurgical management appears to increase repeat presentations.
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COVID-19 , Apendicectomia/efeitos adversos , Apendicectomia/métodos , COVID-19/epidemiologia , Humanos , Pandemias , Estudos Retrospectivos , Provedores de Redes de Segurança , Estados Unidos/epidemiologiaRESUMO
INTRODUCTION: Quality/core measures have been collected for over 10 years. Studies have demonstrated hospital performance is related to postoperative outcomes. We hypothesize that hospital quality measures are associated with long-term survival following surgical resection for hepatocellular carcinoma (HCC). METHODS: The National Cancer Data Base was queried for all HCC cases. Individual hospitals were deidentified. Quality markers were defined as hospital-specific median length of stay (LOS), 30-day mortality rate and readmit rate. A Cox regression stratified by stage estimated survival. To minimize confounding, a landmark analysis was estimated for patients that survived greater than 30 days. RESULTS: A total of 16 202 HCC patients underwent surgical resection and 996 (6.1%) died within 30 days following surgery. Calculated by unique hospital, median 30-day death rate was 4.6% (interquartile range [IQR]: 1.2% to 7.6%). Thirty-day readmit rate was 2.6% (IQR: 0% to 5.9%) and median LOS was 8.0 days (IQR: 6.5 to 9.2). In the multivariate Cox regression, 30-day death rate (hazard ratio [HR], 1.89; 95% confidence interval [CI]: 1.32 to 2.71) and longer LOS (HR, 1.02; 95% CI: 1.01 to 1.02) were associated with worse survival. Higher 30-day readmission rate was associated with improved survival (HR, 0.61; 95% CI, 0.38 to 0.97). CONCLUSIONS: Hospital-level surrogate markers of surgical quality appear to be significantly associated with HCC survival following resection. Patients treated in higher 30-day mortality centers, experienced worse outcomes. Individual hospitals should critically review disease-specific outcomes following resection to identify areas for improvement.
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Biomarcadores , Carcinoma Hepatocelular/mortalidade , Hepatectomia/mortalidade , Neoplasias Hepáticas/mortalidade , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias , Qualidade da Assistência à Saúde , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Seguimentos , Humanos , Tempo de Internação , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Melhoria de Qualidade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND AND OBJECTIVES: Rural patients have poor access to specialists and are less likely to receive evidence-based cancer care. We hypothesized that hepatocellular carcinoma (HCC) patients from rural counties in Texas would be less likely to receive surgical therapy than those from urban areas. METHODS: The Texas Cancer Registry was queried (2000-2008). County-level data included "rural or urban" designation and income variables derived by zip code. Surgical intervention included: (i) ablation, (ii) resection-partial or total lobectomy, or (iii) transplantation. A multinomial logistic regression was created to determine predictors of intervention. RESULTS: Five thousand thirty seven HCC patients were identified (86% urban) for study. A multinomial regression demonstrated, older age, African-American race, and lower income reduced the likelihood of ablation. Younger age, female gender, Caucasian, and Asian/other race predicted surgical resection, or transplantation. Hispanic race was associated with lower likelihood of resection (RRR 0.75) and transplantation (RRR 0.74), whereas African-American race was associated with pronounced decrease for transplantation (RRR 0.48). Area of residency was not predictive of intervention. CONCLUSIONS: Rural residency did not decrease the likelihood of surgical intervention for hepatocellular carcinoma. Race and income continue to be associated with significant treatment disparity. Additional investigation should focus on factors that govern the selection of resection or transplantation for potentially eligible patients.
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Carcinoma Hepatocelular/cirurgia , Hepatectomia/estatística & dados numéricos , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/estatística & dados numéricos , Grupos Raciais , População Rural/estatística & dados numéricos , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Asiático/estatística & dados numéricos , Feminino , Hepatectomia/métodos , Hispânico ou Latino/estatística & dados numéricos , Humanos , Renda , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sistema de Registros , Texas/epidemiologia , População Branca/estatística & dados numéricosRESUMO
BACKGROUND: Disparities in colon cancer survival have been reported to result from advanced stage at diagnosis and delayed therapy. We hypothesized that delays in treatment among medically underserved patients occur as a result of system-level barriers in a safety-net hospital system. MATERIALS AND METHODS: Retrospective review and analysis of colon cancer patients treated in a large safety-net hospital system between May 2008 and May 2012. Data were collected on demographics, stage at diagnosis, time to surgery, time to adjuvant chemotherapy, and vital status. Regression analyses were performed to determine predictors of delays and failure to receive therapy. RESULTS: Of 248 patients treated for colon cancer, 56% (n = 140) had advanced disease at the time of presentation; furthermore, 29.1% of all colectomies for colon cancer were performed on an urgent or emergent basis. Thirty-six patients with stage III and IV disease did not receive chemotherapy (26%). Race, age, gender, and hospice care did not predict receipt of chemotherapy or delays to treatment. Patients with stage I colon cancer had a significantly longer interval between diagnosis and elective surgery when compared with patients with stage II, III, and IV colon cancer, with only 10% (n = 3) undergoing resection sooner than 6 wk after diagnosis. CONCLUSIONS: One in three patients diagnosed with colon cancer in a large safety-net hospital system require urgent or emergent surgery, and one in two present with advanced disease. Reducing disparities should focus on earlier diagnosis of colon cancer and improving access to surgical specialists.
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Adenocarcinoma/terapia , Neoplasias do Colo/terapia , Provedores de Redes de Segurança/estatística & dados numéricos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Since 1990, numerous public repositories of microarray data have been created to store vast genomic data sets. Our hypothesis is that a secondary analysis of an available hepatocellular carcinoma (HCC) public data set could generate new findings and additional hypotheses. METHODS: The Gene Expression Omnibus at the National Center for Biotechnology Information was queried for available data sets specific for 'HCC' and 'clinical data.' Genes that passed filtering and normalization criteria were analyzed using the class comparison and prediction functions in BRB-ArrayTools. Ingenuity pathway analysis software was used to identify potential gene networks up- or down-regulated. RESULTS: The file GDS274, which measured gene expression in primary HCC lesions with or without hepatic metastases from a cohort of Chinese patients, was identified as an appropriate data set and was imported into BRB-ArrayTools. 9984 genes passed filtering criteria. Clinical data demonstrated alpha fetoprotein (AFP) >100 ng/mL predictive of worse survival (HR 5.87, 95% confidence interval: 1.11-31.0). A class comparison between patients with an AFP >100 and those with AFP <100 demonstrated 92 genes to be differentially expressed. Ingenuity pathway analyses demonstrated the top networks associated with the observed gene expression. CONCLUSIONS: Using available HCC microarray data, we identified genes differentially expressed based on AFP >100. Canonical pathway analysis demonstrated functional gene pathways and associated upstream regulators. This study maximizes the use of publicly available data by generating new findings. Secondary analyses of these data sets should be considered by investigators before embarking on new genomic experiments.
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Carcinoma Hepatocelular/metabolismo , Perfilação da Expressão Gênica , Neoplasias Hepáticas/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Humanos , Neoplasias Hepáticas/mortalidade , Pessoa de Meia-Idade , alfa-Fetoproteínas/metabolismoRESUMO
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is often diagnosed at advanced stage and few patients qualify for resection. Effects of barriers to access on outcomes are unknown. We hypothesized that income and rural residence account for delays in treatment and decreased survival. METHODS: Texas Cancer Registry was queried for ICC patients from 2000 to 2008. Median household income (MHI) and urban/rural status were analyzed. Regression analyses were performed for (1) time-to- treatment (TTT), and (2) overall survival (OS). RESULTS: Among 1,089 patients, 20.2% patients resided in rural areas and MHI ranged $24,497-$81,113/year. Primary treatment included surgery for 9.5%, radiation 5.4% and chemotherapy 21.0%. Median TTT was 29 (range 0-235) days. Patients from low-income areas were less likely to receive treatment (below median MHI, 29.7% vs. above median MHI, 37.5%%; P = 0.007). MHI was associated with TTT (per $10,000/year: hazard ratio (HR) = 1.05; 95% CI: 1.01-1.09). Adjusting for stage, MHI was associated with OS (per $10,000/year: HR = 0.97; 95%CI: 0.94-0.99). Rural residence was neither associated with TTT nor OS. CONCLUSION: Overall treatment rates for ICC patients are low. Regional income, not urbanization was associated treatment and survival independent of stage. Further research is needed to determine how regional prosperity relates to care access.
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Neoplasias dos Ductos Biliares/mortalidade , Colangiocarcinoma/mortalidade , Adulto , Idoso , Neoplasias dos Ductos Biliares/epidemiologia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/terapia , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/epidemiologia , Colangiocarcinoma/patologia , Colangiocarcinoma/terapia , Feminino , Humanos , Renda , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Sistema de Registros , Análise de Regressão , TexasRESUMO
Nonalcoholic fatty liver disease (NAFLD) is an emerging epidemic with high prevalence in Western countries. Genome-wide association studies had reported that a variation in the patatin-like phospholipase domain containing 3 (PNPLA3) gene is associated with high susceptibility to NAFLD. However, the relationship between this variation and hepatocellular carcinoma (HCC) has not been well established. We investigated the impact of PNPLA3 genetic variation (rs738409: C>G) on HCC risk and prognosis in the United States by conducting a case-control study that included 257 newly diagnosed and pathologically confirmed Caucasian patients with HCC (cases) and 494 healthy controls. Multivariate logistics and Cox regression models were used to control for the confounding effects of HCC risk and prognostic factors. We observed higher risk of HCC for subjects with a homozygous GG genotype than for those with CC or CG genotypes, the adjusted odds ratio (OR) was 3.21 (95% confidence interval [CI], 1.68-6.41). We observed risk modification among individuals with diabetes mellitus (OR = 19.11; 95% CI, 5.13-71.20). The PNPLA3 GG genotype was significantly associated with underlying cirrhosis in HCC patients (OR = 2.48; 95% CI, 1.05-5.87). Moreover, GG allele represents an independent risk factor for death. The adjusted hazard ratio of the GG genotype was 2.11 (95% CI, 1.26-3.52) compared with CC and CG genotypes. PNPLA3 genetic variation (rs738409: C>G) may determine individual susceptibility to HCC development and poor prognosis. Further experimental investigations are necessary for thorough assessment of the hepatocarcinogenic role of PNPLA3.
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Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/etiologia , Lipase/genética , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Cirrose Hepática/mortalidade , Cirrose Hepática/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida , Estados UnidosRESUMO
BACKGROUND: Breast cancer survival disparities by race are likely multifactorial. In a small pilot cohort, we demonstrated a statistical interaction between age and race. The purpose of this study was to validate earlier findings in a larger, more diverse cohort and to test the hypothesis that breast cancer survival is influenced by the dependent relationship of age and race. METHODS: We conducted a retrospective analysis of a multi-institutional breast cancer database for patients treated between 1999 and 2009. Study variables included age and disease stage at diagnosis, race, treatment (surgery, chemotherapy, radiotherapy, hormone therapy) and overall survival. Statistical analysis and regression models were performed by Stata software. RESULTS: A total of 9,249 patients were included in this study. African American, Hispanic, and Asian patients were more likely to present at a younger age with metastases. African American and Hispanic race were associated with increased mortality after adjusting for stage, age, and treatment. A 2-way interaction between age and race was identified in the Cox regression model (p < 0.001). To further define this interaction, a postestimation analysis was performed to determine the predicted relative hazard for each race with age fixed at 40, 50, 60, 70, and 80 years. At younger ages, the predicted relative hazard was significantly higher for both African American and Hispanic race. CONCLUSIONS: Despite adjusting for stage and treatment differences, African American and Hispanic race predicted poor survival. The effect of age and treatment on breast cancer survival differs across races. Additional research is needed to accurately determine the reasons for worsened survival.
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Negro ou Afro-Americano/estatística & dados numéricos , Neoplasias da Mama/etnologia , Neoplasias da Mama/patologia , Hispânico ou Latino/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/estatística & dados numéricos , Neoplasias da Mama/metabolismo , Intervalos de Confiança , Feminino , Disparidades nos Níveis de Saúde , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Estados Unidos , População Branca/estatística & dados numéricosRESUMO
BACKGROUND: Racial disparities in colorectal cancer persist. Late stage at presentation and lack of stage-specific treatment may be contributing factors. We sought to evaluate the magnitude of disparity remaining after accounting for gender, stage, and treatment using predicted survival models. METHODS: We used institutional tumor registries from a public health system (two hospitals) and a not-for-profit health system (nine hospitals) from 1995 to 2011. Demographics, stage at diagnosis, treatment, and survival were recorded. Hazard ratios (HRs) and predicted HRs were determined by Cox regression and postestimation analyses. RESULTS: There were 6,990 patients: 55.7 % white, 23.6 % African American, 15.1 % Hispanic, and 5.6 % Asian/other. Predictors of survival were surgery (HR 0.57, 95 % confidence interval [CI] 0.46-0.70), chemotherapy (HR 0.7, 95 % CI 0.62-0.79), female gender (HR 0.87, 95 % CI 0.83-0.90), age (HR 1.04, 95 % CI 1.03-1.05), and African American race (HR 3.6, 95 % CI 1.5-8.4). Balancing for stage, gender, and treatment reduced the predicted HRs for African Americans by 28 % and Hispanics by 17 %. In this model, African American and Hispanics still had the worst predicted HRs at younger ages, but whites had the worst predicted HR after age 75. CONCLUSIONS: Gender, stage, and treatment partially accounted for worsened survival in African Americans and Hispanics at all ages. At younger ages, race-related disparities remained which may reflect tumor biology or other unknown factors. Once gender, stage, and treatment are balanced at older ages, the increased mortality observed in whites may be due to factors such as comorbidities. Further system- and patient-level study is needed to investigate reasons for colorectal cancer survival disparities.
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Neoplasias Colorretais/mortalidade , Grupos Raciais/estatística & dados numéricos , Negro ou Afro-Americano/estatística & dados numéricos , Fatores Etários , Idoso , Povo Asiático/estatística & dados numéricos , Neoplasias Colorretais/etnologia , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Hispânico ou Latino/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Fatores de Risco , Programa de SEER , Taxa de Sobrevida , População Branca/estatística & dados numéricosRESUMO
BACKGROUND: Undocumented immigrants have been shown to be predisposed to worse clinical outcomes than the general population. This study examines survival in socioeconomically disadvantaged Hispanic documented and undocumented breast cancer patients. METHODS: Analysis of a prospective breast cancer database of patients treated in a safety-net hospital system. Overall survival was the primary outcome, and advanced stage at diagnosis (regional and metastatic) was a secondary outcome. Survival analysis and multivariate regression modeling were performed. RESULTS: Seven hundred fifty-one breast cancer patients were identified. Undocumented patients presented at an earlier age and were likely to present with advanced stage. After adjusting for covariates, undocumented status was not associated with increased mortality. The diagnosis-to-treatment interval was significantly longer in undocumented patients. CONCLUSIONS: Despite undocumented patients presenting at a younger age, they have similar mortality compared with documented patients. This finding is partly explained by the local treatment afforded by undocumented patients, further studies are necessary to detail the reasons for these differences in presentation and outcome.
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Neoplasias da Mama/etnologia , Neoplasias da Mama/mortalidade , Emigrantes e Imigrantes , Disparidades em Assistência à Saúde , Hispânico ou Latino , Populações Vulneráveis , Adulto , Neoplasias da Mama/patologia , Documentação , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos ProporcionaisRESUMO
Patient prescriber agreements, also known as opioid contracts or opioid treatment agreements, have been recommended as a strategy for mitigating non-medical opioid use (NMOU). The purpose of our study was to characterize the proportion of patients with PPAs, the rate of non-adherence, and clinical predictors for PPA completion and non-adherence. This retrospective study covered consecutive cancer patients seen at a palliative care clinic at a safety net hospital between 1 September 2015 and 31 December 2019. We included patients 18 years or older with cancer diagnoses who received opioids. We collected patient characteristics at consultation and information regarding PPA. The primary purpose was to determine the frequency and predictors of patients with a PPA and non-adherence to PPAs. Descriptive statistics and multivariable logistic regression models were used for the analysis. The survey covered 905 patients having a mean age of 55 (range 18-93), of whom 474 (52%) were female, 423 (47%) were Hispanic, 603 (67%) were single, and 814 (90%) had advanced cancer. Of patients surveyed, 484 (54%) had a PPA, and 50 (10%) of these did not adhere to their PPA. In multivariable analysis, PPAs were associated with younger age (odds ratio [OR] 1.44; p = 0.02) and alcohol use (OR 1.72; p = 0.01). Non-adherence was associated with males (OR 3.66; p = 0.007), being single (OR 12.23; p = 0.003), tobacco (OR 3.34; p = 0.03) and alcohol use (OR 0.29; p = 0.02), contact with persons involved in criminal activity (OR 9.87; p < 0.001), use for non-malignant pain (OR 7.45; p = 0.006), and higher pain score (OR 1.2; p = 0.01). In summary, we found that PPA non-adherence occurred in a substantial minority of patients and was more likely in patients with known NMOU risk factors. These findings underscore the potential role of universal PPAs and systematic screening of NMOU risk factors to streamline care.
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Pancreatic ductal adenocarcinoma (PDAC) presents a 5-year overall survival rate of 11%, despite efforts to improve clinical outcomes in the past two decades. Therapeutic resistance is a hallmark of this disease, due to its dense and suppressive tumor microenvironment (TME). Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a promising local ablative and potential immunomodulatory therapy for PDAC. In this study, we performed RFA in a preclinical tumor-bearing KrasG12D; Trp53R172H/+; Pdx1:Cre (KPC) syngeneic model, analyzed local and abscopal affects after RFA and compared our findings with resected PDAC specimens. We found that RFA reduced PDAC tumor progression in vivo and promoted strong TME remodeling. In addition, we discovered tumor-infiltrating neutrophils determined abscopal effects. Using imaging mass cytometry, we showed that RFA elevated dendritic cell numbers in RFA-treated tumors and promoted a significant CD4+ and CD8+ T-cell abscopal response. In addition, RFA elevated levels of programmed death-ligand 1 (PD-L1) and checkpoint blockade inhibition targeting PD-L1 sustained tumor growth reduction in the context of RFA. This study indicates RFA treatment, which has been shown to increase tumor antigen shedding, promotes antitumor immunity. This is critical in PDAC where recent clinical immunotherapy trials have not resulted in substantial changes in overall survival.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Ablação por Radiofrequência , Humanos , Antígeno B7-H1/farmacologia , Microambiente Tumoral , Neutrófilos , Neoplasias Pancreáticas/patologia , Imunomodulação , Neoplasias PancreáticasRESUMO
The microenvironment that surrounds pancreatic ductal adenocarcinoma (PDAC) is profoundly desmoplastic and immunosuppressive. Understanding triggers of immunosuppression during the process of pancreatic tumorigenesis would aid in establishing targets for effective prevention and therapy. Here, we interrogated differential molecular mechanisms dependent on cell of origin and subtype that promote immunosuppression during PDAC initiation and in established tumors. Transcriptomic analysis of cell-of-origin-dependent epithelial gene signatures revealed that Nt5e/CD73, a cell-surface enzyme required for extracellular adenosine generation, is one of the top 10% of genes overexpressed in murine tumors arising from the ductal pancreatic epithelium as opposed to those rising from acinar cells. These findings were confirmed by IHC and high-performance liquid chromatography. Analysis in human PDAC subtypes indicated that high Nt5e in murine ductal PDAC models overlaps with high NT5E in human PDAC squamous and basal subtypes, considered to have the highest immunosuppression and worst prognosis. Multiplex immunofluorescent analysis showed that activated CD8+ T cells in the PDAC tumor microenvironment express high levels of CD73, indicating an opportunity for immunotherapeutic targeting. Delivery of CD73 small-molecule inhibitors through various delivery routes reduced tumor development and growth in genetically engineered and syngeneic mouse models. In addition, the adenosine receptor Adora2b was a determinant of adenosine-mediated immunosuppression in PDAC. These findings highlight a molecular trigger of the immunosuppressive PDAC microenvironment elevated in the ductal cell of origin, linking biology with subtype classification, critical components for PDAC immunoprevention and personalized approaches for immunotherapeutic intervention. SIGNIFICANCE: Ductal-derived pancreatic tumors have elevated epithelial and CD8+GZM+ T-cell CD73 expression that confers sensitivity to small-molecule inhibition of CD73 or Adora2b to promote CD8+ T-cell-mediated tumor regression. See related commentary by DelGiorno, p. 977.
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Vacinas Anticâncer , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Humanos , Camundongos , Adenosina , Carcinoma Ductal Pancreático/patologia , Terapia de Imunossupressão , Imunoterapia , Neoplasias Pancreáticas/patologia , Microambiente Tumoral , 5'-Nucleotidase/imunologia , Neoplasias PancreáticasRESUMO
BACKGROUND: Populations with low income, economic barriers, and cultural and/or linguistic access barriers to medical care are at risk for worse cancer-related outcomes. Medically underserved patients with hepatocellular carcinoma (HCC) have decreased survival compared with those in the Surveillance, Epidemiology, and End Results database. Given this suboptimal outcome, the high cost of HCC treatment, and unknown risk-to-benefit ratios of invasive therapies, the authors sought to identify a predictive model of extremely poor overall survival (OS). METHODS: A retrospective review of an institutional HCC database was conducted. Payor status, race, treatment, clinicopathologic, and outcome parameters were recorded. The primary outcome was OS <1 month. A logistic regression model predictive of OS <1 month was developed using backward, stepwise elimination and bootstrapping techniques. RESULTS: In total, 337 patients HCC (272 men and 65 women) were identified. Only 4% of patients had Medicare coverage; whereas 96% relied on publicly funded, safety-net health programs. OS <1 month was noted in 90 patients (26.7%). There were no differences in race or sex between patients who had an OS <1 month and those with an OS >1 month. A higher percentage of patients who had an OS <1 month had advanced stage disease and did not receive therapy for HCC. Advanced liver disease, as measured by laboratory parameters and a composite score (Child-Pugh and Model for End-Stage Liver Disease [MELD]), alpha fetoprotein level, creatinine level, disease stage, and lack of treatment were predictors of OS <1 month. CONCLUSIONS: Survival for medically underserved patients with HCC remains poor. Advanced clinical stage and liver disease appear to preclude treatment, and novel methods to identify those who may benefit from palliative care/symptom control may be indicated for patients who are predicted to have poor survival.
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Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Área Carente de Assistência Médica , Modelos Estatísticos , Índice de Gravidade de Doença , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/terapia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Medição de Risco , Taxa de SobrevidaAssuntos
Taxa de Sobrevida , Vitamina D , Neoplasias da Mama , Humanos , Deficiência de Vitamina D , VitaminasRESUMO
BACKGROUND: Racial disparities exist for patients with pancreatic cancer. This observation has primarily been noted in the Surveillance, Epidemiology, and End Results database and has focused primarily on whites and African Americans. We sought to determine if these disparities exist in a local, racially diverse patient population. METHODS: Retrospective review of a pancreatic cancer tumor registry from two hospital systems from 1998 to 2010. Clinicopathologic parameters were recorded. Statistical analysis was performed by analysis of variance, Chi square test, Kaplan-Meier survival analysis, log rank test, and regression models. RESULTS: A total of 1039 patients were identified for this study. Hispanic and African American patients presented at an earlier age when compared to whites. There was no difference in gender or stage at presentation between racial groups. Adjusted for stage, race was predictive of chemotherapy administration. Independent predictors of increased mortality included male gender, African American race, stage at diagnosis, and older age. CONCLUSIONS: Despite adjusting for covariates, survival remains lowest for African American patients. Further investigation is needed to understand the effect of race and how it mediates treatment and survival in those with pancreatic cancer.