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1.
Gut ; 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849943

RESUMO

OBJECTIVE: Recent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) and alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). However, they have not been comprehensively evaluated, especially among small NF-PanNETs (≤2.0 cm). Moreover, their status in neuroendocrine tumours (NETs) from other sites remains unknown. DESIGN: An international cohort of 1322 NETs was evaluated by immunolabelling for ARX/PDX1 and ATRX/DAXX, and telomere-specific fluorescence in situ hybridisation for ALT. This cohort included 561 primary NF-PanNETs, 107 NF-PanNET metastases and 654 primary, non-pancreatic non-functional NETs and NET metastases. The results were correlated with numerous clinicopathological features including relapse-free survival (RFS). RESULTS: ATRX/DAXX loss and ALT were associated with several adverse prognostic findings and distant metastasis/recurrence (p<0.001). The 5-year RFS rates for patients with ATRX/DAXX-negative and ALT-positive NF-PanNETs were 40% and 42% as compared with 85% and 86% for wild-type NF-PanNETs (p<0.001 and p<0.001). Shorter 5-year RFS rates for ≤2.0 cm NF-PanNETs patients were also seen with ATRX/DAXX loss (65% vs 92%, p=0.003) and ALT (60% vs 93%, p<0.001). By multivariate analysis, ATRX/DAXX and ALT status were independent prognostic factors for RFS. Conversely, classifying NF-PanNETs by ARX/PDX1 expression did not independently correlate with RFS. Except for 4% of pulmonary carcinoids, ATRX/DAXX loss and ALT were only identified in primary (25% and 29%) and NF-PanNET metastases (62% and 71%). CONCLUSIONS: ATRX/DAXX and ALT should be considered in the prognostic evaluation of NF-PanNETs including ≤2.0 cm tumours, and are highly specific for pancreatic origin among NET metastases of unknown primary.

3.
Ann Surg Oncol ; 28(5): 2438-2446, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33523364

RESUMO

AIMS: National studies have demonstrated disparities in the treatment and survival of pancreatic cancer patients based on socioeconomic status (SES). This study aimed to identify specific differences in perioperative management and outcomes based on patient SES and to study the role of a multidisciplinary clinic (MDC) in mitigating any variations. METHODS: The study analyzed patients undergoing pancreaticoduodenectomy for pancreatic ductal adenocarcinoma in a large hospital system. The patients were categorized into groups of high and low SES and whether they were managed by the authors' pancreatic cancer MDC or not. The study compared differences in disease characteristics, receipt of multimodality therapy, perioperative outcomes, and recurrence-free and overall survival. RESULTS: Of the 162 low-SES patients and 119 high-SES patients, 54% were managed in the MDC. Outside the MDC, low-SES patients were less likely to receive neoadjuvant chemotherapy and had less minimally invasive surgery, a longer OR time, less enhanced recovery participation, and more major complications (p < 0.05). No SES disparities were observed among the MDC patients. Despite similar tumor characteristics, the low-SES patients had inferior median overall survival (21 vs 32 months; p = 0.005), but the MDC appeared to eliminate this disparity. Low SES correlated with inferior survival for the non-MDC patients (17 vs 32 months; p < 0.001), but not for the MDC patients (24 vs 25 months; p = 0.33). These findings persisted in the multivariable analysis. CONCLUSION: A pancreatic cancer MDC standardizes treatment decisions, eliminates disparities in surgical outcomes, and improves survival for low-SES patients.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/cirurgia , Disparidades em Assistência à Saúde , Humanos , Recidiva Local de Neoplasia , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Classe Social
5.
Gastrointest Endosc ; 94(1): 160-168.e3, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33497642

RESUMO

BACKGROUND AND AIMS: During the severe acute respiratory syndrome coronavirus 2 pandemic, N95 filtering facepiece respirator (FFR) use was required while performing aerosol-generating procedures. We studied the physiologic effects of N95 FFR use in a cohort of gastroenterologists performing simulated colonoscopies. METHODS: Data collection and comparisons included (1) symptoms and change in vital signs in 12 gastroenterologists performing simulated colonoscopy for 60 minutes while wearing a surgical mask (SM) and faceshield (FS); N95 FFR, SM, and FS; and powered air-purifying respirator (PAPR) and (2) respiratory belt plethysmography and continuous electrocardiographic frequency-based heart rate (HR) variability indices including very low frequency power (measures intracardiac sympathetic tone) and low frequency to high frequency ratios (intracardiac sympathetic to vagal ratio) in 11 gastroenterologists performing simulated colonoscopy while wearing an SM (15 minutes), N95 FFR and SM (60 minutes), and SM (15 minutes) in rapid sequence. RESULTS: Ten of 12 gastroenterologists (83%) reported symptoms with N95 FFR use, most commonly breathing difficulty, frustration, fatigue, and headache. Nine of these gastroenterologists (75%) had associated significant HR elevation. Respiratory peak to trough measurement showed a significant increase (F(2) = 7.543, P = .004) during the N95 FFR stage, which resolved after removal of the N95 FFR. Although not statistically different, all gastroenterologists showed a decrease in sympathetic to vagal ratios and an increase in intracardiac sympathetic effects in the N95 FFR stage. PAPR use was better tolerated but was associated with headache and elevated HR in 4 gastroenterologists (33%). CONCLUSIONS: N95 FFR use by gastroenterologists is associated with development of acute physiologic changes and symptoms.


Assuntos
COVID-19 , Gastroenterologistas , Respiradores N95 , Exposição Ocupacional , Colonoscopia , Eletrocardiografia , Frequência Cardíaca , Humanos , Exposição Ocupacional/prevenção & controle
6.
Artigo em Inglês | MEDLINE | ID: mdl-33278573

RESUMO

BACKGROUND & AIMS: The assessment of therapeutic response after neoadjuvant treatment and pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) has been an ongoing challenge. Several limitations have been encountered when employing current grading systems for residual tumor. Considering endoscopic ultrasound (EUS) represents a sensitive imaging technique for PDAC, differences in tumor size between preoperative EUS and postoperative pathology after neoadjuvant therapy were hypothesized to represent an improved marker of treatment response. METHODS: For 340 treatment-naïve and 365 neoadjuvant-treated PDACs, EUS and pathologic findings were analyzed and correlated with patient overall survival (OS). A separate group of 200 neoadjuvant-treated PDACs served as a validation cohort for further analysis. RESULTS: Among treatment-naïve PDACs, there was a moderate concordance between EUS imaging and postoperative pathology for tumor size (r = 0.726, P < .001) and AJCC 8th edition T-stage (r = 0.586, P < .001). In the setting of neoadjuvant therapy, a decrease in T-stage correlated with improved 3-year OS rates (50% vs 31%, P < .001). Through recursive partitioning, a cutoff of ≥47% tumor size reduction was also found to be associated with improved OS (67% vs 32%, P < .001). Improved OS using a ≥47% threshold was validated using a separate cohort of neoadjuvant-treated PDACs (72% vs 36%, P < .001). By multivariate analysis, a reduction in tumor size by ≥47% was an independent prognostic factor for improved OS (P = .007). CONCLUSIONS: The difference in tumor size between preoperative EUS imaging and postoperative pathology among neoadjuvant-treated PDAC patients is an important prognostic indicator and may guide subsequent chemotherapeutic management.

7.
Ann Surg ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33201115

RESUMO

OBJECTIVE: To evaluate the significance of UDD in IPMNs. BACKGROUND: The uncinate process of the pancreas has an independent ductal drainage system. International consensus guidelines of IPMNs still consider it as a branch-duct, even though it is the main drainage system for the uncinate process. METHODS: A retrospective review of all surgically treated IPMNs at our institution after 2008 was performed. Preoperative radiological studies were reviewed by an abdominal radiologist who was blinded to the pathological results. In addition to the Fukuoka criteria, presence of UDD was recorded. Using multivariate analysis, the pathological significance of UDD in predicting advanced neoplasia [high grade dysplasia or invasive carcinoma (HGD/IC)] was determined. RESULTS: Two hundred sixty patients were identified (mean age at diagnosis was 68 years and 49% were females): 122 (47%) had HGD/IC. UDD was noted in 59 (23%), of which 36 (61%) had HGD/IC (P < 0.003). On multivariate analysis, UDD was an independent predictor of HGD/IC (odds ratio = 2.99, P < 0.04). Subgroup analysis on patients with IPMNs confined to the dorsal portion of the gland (n = 161), also demonstrated UDD to be a significant predictor of HGD/IC in those remote lesions (odds ratio: 4.41, P = 0.039). CONCLUSIONS: This is the largest study to evaluate the significance of UDD in IPMNs and shows it to be a high-risk feature. This association persisted for remote IPMNs limited to the dorsal pancreas, suggesting UDD may be associated with an aggressive phenotype even in remote IPMN lesions.

8.
Sci Adv ; 6(27): eaba4526, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32656339

RESUMO

Chronic inflammatory gastric reflux alters the esophageal microenvironment and induces metaplastic transformation of the epithelium, a precancerous condition termed Barrett's esophagus (BE). The microenvironmental niche, which includes the extracellular matrix (ECM), substantially influences cell phenotype. ECM harvested from normal porcine esophageal mucosa (eECM) was formulated as a mucoadhesive hydrogel, and shown to largely retain basement membrane and matrix-cell adhesion proteins. Dogs with BE were treated orally with eECM hydrogel and omeprazole (n = 6) or omeprazole alone (n = 2) for 30 days. eECM treatment resolved esophagitis, reverted metaplasia to a normal, squamous epithelium in four of six animals, and downregulated the pro-inflammatory tumor necrosis factor-α+ cell infiltrate compared to control animals. The metaplastic tissue in control animals (n = 2) did not regress. The results suggest that in vivo alteration of the microenvironment with a site-appropriate, mucoadhesive ECM hydrogel can mitigate the inflammatory and metaplastic response in a dog model of BE.

9.
Bull Am Meteorol Soc ; 101(3): E323-E340, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32483389

RESUMO

Severe weather events including tornadoes, damaging winds, hail, and their combination produce changes in land surface vegetation and urban settings that are frequently observed through remote sensing. Capabilities continue to improve through a growing constellation of governmental and commercial assets, increasing the spatial resolution of visible, near to shortwave infrared, and thermal infrared remote sensing. Here, we highlight cases where visual interpretation of imagery benefitted severe weather damage assessments made within the NOAA/NWS Damage Assessment Toolkit. Examples demonstrate utility of imagery in assessing tracks and changes in remote areas where staffing limitations or access prevent a ground-based assessment.

10.
Histopathology ; 77(3): 481-491, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32431062

RESUMO

AIMS: Abnormal p53 protein expression detected by immunohistochemistry (IHC) in Barrett's oesophagus (BO) is reported to be a prognostic biomarker for progression to high-grade dysplasia (HGD) or oesophageal adenocarcinoma (OAC). We evaluated our use of p53 IHC for patients with BO under surveillance from 2010 to 2016 in a single academic institution. METHODS AND RESULTS: We identified 78 patients under surveillance for BO who had biopsies evaluated for abnormal p53 expression in conjunction with routine histology and 892 patients who had histological evaluation alone. All available p53 IHC slides were rescored as wild-type or abnormal. We evaluated the risk of subsequent diagnosis with HGD and OAC. p53-tested patients were significantly more likely to be diagnosed with indefinite dysplasia (IND) or low-grade dysplasia (LGD), compared to patients who were not tested (79.5 versus 10.8%, P = 7.4 × 10-40 ). Almost half (46.9%) of patients with abnormal p53 expression were diagnosed with HGD or OAC within 5 years, compared to 5.9% with wild-type p53, and 7.6% of patients not tested (P = 2.6 × 10-18 ). However, this difference was heavily influenced by other risk factors, including dysplasia grade, in multivariate analyses. In the subgroup of patients diagnosed with IND (n = 109), abnormal p53 expression was associated with a fourfold increase (1.2-13.3, P = 0.023) in risk of HGD/OAC relative to untested patients diagnosed with IND, independent of other risk factors. CONCLUSION: In patients under surveillance for BO in a single academic institution, we found evidence that selective use of p53 IHC in conjunction with routine histology modestly improved risk stratification by identifying patients with IND at higher risk of a subsequent diagnosis of HGD or OAC.


Assuntos
Esôfago de Barrett/patologia , Biomarcadores Tumorais/análise , Lesões Pré-Cancerosas/patologia , Proteína Supressora de Tumor p53/biossíntese , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
Am J Gastroenterol ; 115(6): 843-852, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32079863

RESUMO

INTRODUCTION: A risk prediction test was previously validated to predict progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). The aim of our study was to independently validate this test to predict the risk of progression to HGD/EAC in BE patients with nondysplastic (ND), indefinite for dysplasia and low-grade dysplasia (LGD). METHODS: A single-blinded, case-control study was conducted to stratify patients with BE as low, intermediate, or high risk for progression to HGD/EAC within 5 years using a previously described risk prediction test. Patients with BE who progressed to HGD/EAC after at least 1 year (n = 58) were matched to patients undergoing surveillance without progression (n = 210, median surveillance 7 years). Baseline biopsies with subspecialist diagnoses of ND, indefinite for dysplasia, or LGD were tested in a blinded manner, and the predictive performance of the test was assessed. RESULTS: This risk prediction test stratified patients with BE based on progression risk with the high-risk group at 4.7-fold increased risk for HGD/EAC compared with the low-risk group (95% confidence interval 2.5-8.8, P < 0.0001). Prevalence-adjusted positive predictive value at 5 years was 23%. The high-risk class and male sex provided predictive power that was independent of pathologic diagnosis, age, segment length, and hiatal hernia. Patients with ND BE who scored high risk progressed at a higher rate (26%) than patients with subspecialist-confirmed LGD (21.8%) at 5 years. DISCUSSION: A risk prediction test identifies patients with ND BE who are at high risk for progression to HGD/EAC and may benefit from early endoscopic therapy or increased surveillance.


Assuntos
Adenocarcinoma/epidemiologia , Esôfago de Barrett/patologia , Neoplasias Esofágicas/epidemiologia , Esôfago/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Esôfago de Barrett/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Ciclo-Oxigenase 2/metabolismo , Progressão da Doença , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Esôfago/metabolismo , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Processamento de Imagem Assistida por Computador , Queratina-20/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Masculino , Microscopia de Fluorescência , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Racemases e Epimerases/metabolismo , Receptor ErbB-2/metabolismo , Medição de Risco , Proteína Supressora de Tumor p53/metabolismo , Conduta Expectante
12.
Gut ; 69(1): 52-61, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30971436

RESUMO

OBJECTIVE: Despite improvements in imaging, serum CA19-9 and pathological evaluation, differentiating between benign and malignant bile duct strictures remains a diagnostic conundrum. Recent developments in next-generation sequencing (NGS) have opened new opportunities for early detection and management of cancers but, to date, have not been rigorously applied to biliary specimens. DESIGN: We prospectively evaluated a 28-gene NGS panel (BiliSeq) using endoscopic retrograde cholangiopancreatography-obtained biliary specimens from patients with bile duct strictures. The diagnostic performance of serum CA19-9, pathological evaluation and BiliSeq was assessed on 252 patients (57 trainings and 195 validations) with 346 biliary specimens. RESULTS: The sensitivity and specificity of BiliSeq for malignant strictures was 73% and 100%, respectively. In comparison, an elevated serum CA19-9 and pathological evaluation had sensitivities of 76% and 48%, and specificities of 69% and 99%, respectively. The combination of BiliSeq and pathological evaluation increased the sensitivity to 83% and maintained a specificity of 99%. BiliSeq improved the sensitivity of pathological evaluation for malignancy from 35% to 77% for biliary brushings and from 52% to 83% for biliary biopsies. Among patients with primary sclerosing cholangitis (PSC), BiliSeq had an 83% sensitivity as compared with pathological evaluation with an 8% sensitivity. Therapeutically relevant genomic alterations were identified in 20 (8%) patients. Two patients with ERBB2-amplified cholangiocarcinoma received a trastuzumab-based regimen and had measurable clinicoradiographic response. CONCLUSIONS: The combination of BiliSeq and pathological evaluation of biliary specimens increased the detection of malignant strictures, particularly in patients with PSC. Additionally, BiliSeq identified alterations that may stratify patients for specific anticancer therapies.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Doenças Biliares/diagnóstico , Doenças Biliares/genética , Doenças Biliares/patologia , Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Constrição Patológica/diagnóstico , Constrição Patológica/genética , Diagnóstico Diferencial , Feminino , Humanos , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/genética , Cirrose Hepática Biliar/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Manejo de Espécimes/métodos , Adulto Jovem
13.
Gastroenterology ; 158(3): 573-582.e2, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31678302

RESUMO

BACKGROUND & AIMS: Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreas and bile duct contain epithelial cells with numerous, large mitochondria and are cystic precursors to pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA), respectively. However, IOPNs do not have the genomic alterations found in other pancreatobiliary neoplasms. In fact, no recurrent genomic alterations have been described in IOPNs. PDACs without activating mutations in KRAS contain gene rearrangements, so we investigated whether IOPNs have recurrent fusions in genes. METHODS: We analyzed 20 resected pancreatic IOPNs and 3 resected biliary IOPNs using a broad RNA-based targeted sequencing panel to detect cancer-related fusion genes. Four invasive PDACs and 2 intrahepatic CCAs from the same patients as the IOPNs, were also available for analysis. Samples of pancreatic cyst fluid (n = 5, collected before surgery) and bile duct brushings (n = 2) were analyzed for translocations. For comparison, we analyzed pancreatobiliary lesions from 126 patients without IOPN (controls). RESULTS: All IOPNs evaluated were found to have recurring fusions of ATP1B1-PRKACB (n = 13), DNAJB1-PRKACA (n = 6), or ATP1B1-PRKACA (n = 4). These fusions also were found in corresponding invasive PDACs and intrahepatic CCAs, as well as in matched pancreatic cyst fluid and bile duct brushings. These gene rearrangements were absent from all 126 control pancreatobiliary lesions. CONCLUSIONS: We identified fusions in PRKACA and PRKACB genes in pancreatic and biliary IOPNs, as well as in PDACs and pancreatic cyst fluid and bile duct cells from the same patients. We did not identify these gene fusions in 126 control pancreatobiliary lesions. These fusions might be used to identify patients at risk for IOPNs and their associated invasive carcinomas.


Assuntos
Neoplasias dos Ductos Biliares/genética , Carcinoma Ductal Pancreático/genética , Colangiocarcinoma/genética , Subunidades Catalíticas da Proteína Quinase Dependente de AMP Cíclico/genética , Neoplasias Intraductais Pancreáticas/genética , Neoplasias Pancreáticas/genética , Adulto , Idoso , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos , Feminino , Fusão Gênica , Rearranjo Gênico , Proteínas de Choque Térmico HSP40/genética , Humanos , Masculino , Pessoa de Meia-Idade , Cisto Pancreático/genética , Neoplasias Intraductais Pancreáticas/patologia , Neoplasias Pancreáticas/patologia , ATPase Trocadora de Sódio-Potássio/genética
15.
Gastrointest Endosc ; 90(2): 213-214, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31327336
16.
AJR Am J Roentgenol ; 211(5): 1020-1025, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30160983

RESUMO

OBJECTIVE: The objective of this study was to identify imaging characteristics in patients with known pancreatic neuroendocrine tumors (PanNETs) that predict the alternative lengthening of telomeres (ALT) phenotype by blinded retrospective review of preoperative multiphasic CT scans. MATERIALS AND METHODS: For this retrospective study of 121 preoperative CT examinations of patients with resected PanNETs, two radiologists independently reviewed the CT examinations for tumor characteristics including size, shape, cystic or necrotic elements, calcifications, invasion of adjacent organs and vessels, biliary duct dilatation, pancreatic duct dilatation, and hepatic metastases. Univariate analysis of association of CT characteristics with ALT phenotype was performed with Fisher exact tests or t tests, and multivariate analysis was assessed by multiple logistic regression. RESULTS: Univariate analysis showed that the following CT features were significantly associated with the ALT phenotype: lobulated or irregular tumor shape (p = 0.001), tumor necrosis (p = 0.002), vascular invasion (p < 0.001), pancreatic duct dilatation (p < 0.001), and hepatic metastasis (p < 0.001). Multivariate analysis found that the combination of pancreatic duct dilatation, hepatic metastasis, and size of tumor ≥ 3 cm was a strong predictor of ALT phenotype (odds ratio = 20.3; 95% CI = 2.3-176.3; AUC = 0.58; p = 0.006). CONCLUSION: This study showed that several preoperative CT features of PanNETs are associated with the ALT phenotype, which is known to predict poor prognosis. Additionally, CT findings of intratumoral calcifications and metastases predicted poor survival independent of the ALT status.


Assuntos
Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/genética , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/genética , Homeostase do Telômero , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Fenótipo , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos Retrospectivos
17.
Gastroenterol Res Pract ; 2018: 2380596, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29967636

RESUMO

Background: Adolescent obesity is a national epidemic that recently has been shown to increase risk for pancreatic adenocarcinoma (PC) and is associated with an earlier age of PC onset. We hypothesized that PC patients who are overweight or obese at age 18 would have an earlier age of PC onset. Methods: Retrospective review of 531 patients in our PC registry was completed. Self-reported weight at age 18 and maximum lifetime weight were used to calculate body mass index (BMI) at age 18 (BMI-18) and maximum lifetime BMI. Results: Complete BMI and baseline covariate data was available in 319 PC patients. Mean age (in years) of PC diagnosis for patients whose BMI-18 was overweight (64.0) or obese (59.9) was significantly different when compared to patients with a normal BMI-18 (66.7). No significant difference was observed in the mean age of PC diagnosis in those patients who maintained a normal BMI-18 when compared to those patients who subsequently became overweight or obese (67.0 versus 66.6; p = 0.65). Conclusions: An elevated BMI at age 18 is associated with an earlier age of PC onset and should be factored into determining the optimal age of beginning screening for patients at high risk for PC.

18.
Gastrointest Endosc ; 88(5): 807-815.e2, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29944863

RESUMO

BACKGROUND AND AIMS: The diagnosis of low-grade dysplasia (LGD) in Barrett's esophagus (BE) is subject to substantial interobserver variation. Our central aim in this study is to compare independent pathology practices using objective measures of BE risk stratification proficiency, including frequency of diagnosis and rate of progression, with high-grade dysplasia (HGD) or adenocarcinoma (EAC) after the first diagnosis of LGD. METHODS: We retrospectively evaluated over 29,000 endoscopic biopsy cases to identify 4734 patients under endoscopic biopsy surveillance for BE in a healthcare system with multiple independent pathology practices: a subspecialized GI pathology group (SSGI; 162 BE cases per pathologist annually), 3 high BE volume general surgical pathology practices (GSPs; >50 BE cases per pathologist annually), and multiple low BE volume GSPs (10.6 BE cases per pathologist annually). We measured LGD diagnosis frequencies and rates of diagnostic progression to HGD or EAC in patients diagnosed with LGD. RESULTS: The proportion of all BE cases diagnosed as LGD (LGD/BE diagnosis ratio) ranged from 1.1% to 6.8% in the different hospital settings (P < .001). The cumulative proportion of patients with HGD or EAC within 2 years of the first diagnosis of LGD was 35.3% in the SSGI and ranged from 1.4% to 14.3% in the GSPs (P < .001). LGD diagnosed by the GSP with the lowest LGD/BE diagnosis ratio had an adjusted risk of progression similar to LGD diagnosed by subspecialists (hazard ratio, .42; 95% CI, .06-3.03). However, when LGD was diagnosed by other generalists, the adjusted risk of progression was 79% to 91% lower than subspecialists (P < .001). When LGD was diagnosed in a low-volume GSP practice, the risk of progression was not significantly increased relative to patients with nondysplastic BE (hazard ratio, 1.3; 95% CI, .4-3.9). CONCLUSIONS: General surgical pathologists and subspecialists show highly significant differences with respect to LGD/BE ratio, risk of progression relative to nondysplastic BE, crude annual progression rates, and the cumulative 2-year progression rate after LGD. These metrics can be used to assess proficiency in BE risk stratification in historical cases. Some general practitioners were able to achieve results similar to subspecialists. General surgical pathologists with little annual experience evaluating BE biopsy specimens did not successfully risk stratify patients with BE.


Assuntos
Esôfago de Barrett/patologia , Progressão da Doença , Neoplasias Esofágicas/patologia , Patologia/normas , Lesões Pré-Cancerosas/patologia , Idoso , Esôfago de Barrett/fisiopatologia , Esôfago de Barrett/cirurgia , Biópsia por Agulha , Neoplasias Esofágicas/fisiopatologia , Neoplasias Esofágicas/cirurgia , Esofagoscopia/métodos , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Patologia/tendências , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas
19.
Gastroenterology ; 154(8): 2060-2063.e8, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29486199

RESUMO

Despite prognostic grading and staging systems, it is a challenge to predict outcomes for patients with pancreatic neuroendocrine tumors (PanNETs). Sequencing studies of PanNETs have identified alterations in death domain-associated protein (DAXX) and alpha-thalassemia/mental retardation X-linked chromatin remodeler (ATRX). In tumors, mutations in DAXX or ATRX and corresponding loss of protein expression correlate with shorter times of disease-free survival and disease-specific survival of patients. However, DAXX or ATRX proteins were lost in only 50% of distant metastases analyzed. We performed whole-exome sequencing analyses of 20 distant metastases from 20 patients with a single nonsyndrome, nonfunctional PanNET. We found distant metastases contained alterations in multiple endocrine neoplasia type 1 (MEN1) (n = 8), ATRX (n = 5), DAXX (n = 5), TSC2 (n = 3), and DEP domain containing 5 (DEPDC5) (n = 3). We found copy number loss of cyclin dependent kinase inhibitor 2A (CDKN2A) in 15 metastases (75%) and alterations in genes that regulate chromatin remodeling, including set domain containing 2 (SETD2) (n = 4), AT-rich interaction domain 1A (ARID1A) (n = 2), chromodomain helicase DNA binding protein 8 (CHD8) (n = 2), and DNA methyl transferase 1 (DNMT1) (n = 2). In a separate analysis of 347 primary PanNETs, we found loss or deletion of DAXX and ATRX, disruption of SETD2 function (based on loss of H3 lysine 36 trimethylation), loss of ARID1A expression or deletions in CDKN2A in 81% of primary PanNETs with distant metastases. Among patients with loss or deletion of at least 1 of these proteins or genes, 39% survived disease-free for 5 years and 44% had disease-specific survival times of 10 years. Among patients without any of these alterations, 98% survived disease-free for 5 years and 95% had disease-specific survival times of 10 years. Therefore, primary PanNETs with loss of DAXX, ATRX, H3 lysine 36 trimethylation, ARID1A, and/or CDKN2A associate with shorter survival times of patients. Our findings indicate that alterations in chromatin-remodeling genes and CDKN2A contribute to metastasis of PanNETs.


Assuntos
Biomarcadores Tumorais/genética , Inibidor de Quinase Dependente de Ciclina p18/genética , Tumores Neuroendócrinos/genética , Proteínas Nucleares/genética , Neoplasias Pancreáticas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Montagem e Desmontagem da Cromatina/genética , Inibidor p16 de Quinase Dependente de Ciclina , Variações do Número de Cópias de DNA , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Sequenciamento Completo do Exoma
20.
Abdom Radiol (NY) ; 43(9): 2351-2368, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29404638

RESUMO

Cystic neoplasms in the pancreas are encountered frequently on imaging, often detected incidentally during evaluation for other conditions. They can have a variety of clinical and imaging presentations, and similarly, wide-ranging prognostic and treatment implications. In the majority, imaging helps in diagnosis of pancreatic cystic neoplasms (PCNs) and guides management decisions. But, a significant minority of the PCNs remain indeterminate. There have been multiple recent advances in biomarkers and molecular genetics which will likely prove helpful in risk stratification of PCNs. Several prominent national and international societies, as well as consensus groups have put forth recommendations to help guide management of PCNs. The purpose of this article is to discuss the role of imaging in evaluation of PCNs, review the recent advances in molecular genetics and pancreatic cyst fluid analysis, and analyze the pros and cons of major evidence-based and consensus guidelines for management of PCNs.


Assuntos
Cistadenoma Seroso/diagnóstico por imagem , Cistadenoma Seroso/genética , Cisto Pancreático/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/genética , Guias de Prática Clínica como Assunto , Humanos , Cisto Pancreático/genética
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