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2.
Pediatr Blood Cancer ; 69(9): e29786, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35593027

RESUMO

BACKGROUND: Tyrosine kinase inhibitors (TKIs) improve outcomes for pediatric malignancies characterized by specific gene rearrangements and mutations; however, little is known about the long-term impact of TKI exposure. Our objective was to assess the incidence and type of late-onset TKI-related toxicities in children with chronic myeloid leukemia (CML). METHODS: We reviewed medical records from patients diagnosed with CML between 2006 and 2019 at <21 years of age and prescribed one or more TKIs. Patients treated with stem cell transplant were excluded. Outcomes were captured beginning at 1 year after CML diagnosis. Outcome incidence was described overall and stratified by TKI exposure during the data-capture period. RESULTS: Twenty-two eligible TKI-exposed patients with CML were identified. The median follow-up was 6.0 years (range: 2.2-14.3). All pericardial (n = 3) or pleural (n = 3) effusion outcomes occurred in patients treated with TKIs during the data-capture period. Other outcomes included hypertension (n = 2), ectopy on electrocardiogram (n = 2), and gastrointestinal bleed (n = 1). All outcomes were graded as mild to moderate: some resulted in a temporary discontinuation of TKI, but none led to a change in TKI. No differences were noted in outcome incidence by type of TKI exposure. CONCLUSIONS: TKIs have substantially improved prognosis for subsets of childhood leukemia, but there are limited long-term data to inform exposure-based risk for late-onset complications and screening. Our results suggest that TKI-exposed survivors may be at risk for long-term outcomes that extend well into survivorship.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva , Criança , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Prognóstico , Inibidores de Proteínas Quinases/efeitos adversos
3.
Gastrointest Endosc ; 92(2): 284-292.e2, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32126220

RESUMO

BACKGROUND AND AIMS: An increasing number of patients are undergoing GI endoscopic procedures with active prescriptions for direct oral anticoagulants (DOACs). DOACs have been associated with a higher risk of GI bleeding (GIB) compared with warfarin. Our aims were to compare the risk of postendoscopic GIB and thromboembolic (TE) events among patients on DOACs versus warfarin. METHODS: We conducted a retrospective cohort study of patients aged 18 years or older in a large integrated health care system in Southern California, who had undergone an outpatient GI endoscopic procedure and were taking a DOAC or warfarin between January 1, 2013, and October 1, 2019. We compared bleeding and thrombosis risk in the 30 days after the endoscopic procedure between the warfarin and DOAC groups using multivariate logistic regression analysis adjusted for covariates. RESULTS: Between January 1, 2013, and October 1, 2019, we identified 6765 outpatient GI endoscopic procedures in which patients received preprocedure prescriptions for either a DOAC (1587) or warfarin (5178). Overall, there was no significant difference in postprocedure GIB (odds ratio [OR], 1.165; 95% confidence interval [CI], 0.88-1.55; P = .291) or TE (OR, 0.929; 95% CI, 0.64-1.35; P = .703) between the DOAC and warfarin groups). Subgroup analysis revealed a higher risk of GIB associated with DOAC specifically with EGD procedures (OR, 1.8; 95% CI, 1.15-2.83; P = .011). CONCLUSIONS: There was no significant difference in the overall postendoscopic risk of GIB and TE events among patients with preprocedure use of DOACs compared with patients on warfarin. There may be a higher risk of GIB in patients taking DOACs and undergoing EGD.


Assuntos
Inibidores do Fator Xa , Varfarina , Administração Oral , Adolescente , Anticoagulantes/efeitos adversos , Endoscopia , Inibidores do Fator Xa/uso terapêutico , Humanos , Estudos Retrospectivos , Varfarina/efeitos adversos
4.
Dig Dis Sci ; 64(3): 890-897, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30094622

RESUMO

BACKGROUND AND AIMS: To evaluate impact of ambulatory triglyceride levels on risk of recurrent pancreatitis in patients with hypertriglyceridemic pancreatitis. METHODS: We conducted a longitudinal retrospective cohort study of patients with serum triglyceride level ≥ 500 mg/dL during index hospitalization for acute pancreatitis within a regional integrated healthcare system between 2006 and 2013 (follow-up through 2015). Cases were identified based on combination of diagnosis codes and serum amylase/lipase. We used multivariable robust Poisson regression to determine independent effect of baseline (first outpatient) triglyceride measurement on risk of recurrent pancreatitis. Ambulatory triglyceride levels were categorized as normal (0-200 mg/dL), moderately elevated (201-500 mg/dL), and highly elevated (> 500 mg/dL). We further assessed factors related to likelihood of normalization of serum triglycerides (< 200 mg/dL) in the outpatient setting. RESULTS: One hundred and fifty-one patients met study inclusion criteria with median follow-up of 3 years. Overall, 45 (29.8%) patients experienced at least 1 recurrent attack with 25 (16.6%) experiencing multiple episodes. In multivariable analysis, patients that continued to have moderately elevated ((adjusted rate ratio RR 5.47 (95% CL 1.80, 16.65)) as well as highly elevated (RR 8.45 (2.55, 27.96)) triglycerides were at increased risk of disease recurrence compared to patients that achieved normalization. Patients with triglyceride measurement performed within 30 days from discharge were more likely to achieve normalization, 40 versus 26%, p = 0.03. CONCLUSIONS: For patients with hypertriglyceridemic pancreatitis, even modest elevation in subsequent triglyceride levels was associated with increased risk of recurrence. Future efforts should focus on ensuring timely care in the outpatient setting with a goal of normalizing triglycerides.


Assuntos
Hipertrigliceridemia/complicações , Pancreatite/etiologia , Triglicerídeos/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/diagnóstico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pancreatite/diagnóstico , Prognóstico , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto Jovem
6.
Clin Gastroenterol Hepatol ; 15(4): 511-517, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27939654

RESUMO

BACKGROUND AND AIMS: Limited data are available on risk factors for gastric cancer in the United States. We aimed to characterize risk for gastric cancer based on race/ethnicity and additional established risk factors. METHODS: We conducted a retrospective cohort study from 2008 to 2014 from an integrated health care system in Southern California to assess incidence of gastric cancer by race/ethnicity. We then conducted an age- and sex-matched case-cohort study to evaluate additional risk factors: Helicobacter pylori infection, tobacco use, family history, obesity, language, and socioeconomic status. Subgroup analysis was performed for language and socioeconomic status by race/ethnicity. RESULTS: The incidence of gastric cancer in the reference (non-Hispanic white) population was 8.2 (95% confidence interval [CI], 7.7-8.7) cases per 100,000 person-years. Incidence values for Asians, Hispanics, and non-Hispanic black persons were higher: 12.7 (95% CI, 11.1-14.3), 12.7 (95% CI, 11.7-13.7), and 11.8 (95% CI, 10.3-13.2) cases per 100,000 person-years, respectively (all P < .0001). In logistic regression analysis, we found race/ethnicity to be an independent risk factor for gastric cancer; the odds ratio (OR) for non-Hispanic black persons was 1.5 (95% CI, 1.22-1.72; P < .0001), the OR for Hispanics was 1.4 (95% CI, 1.22-1.57; P < .0001), and the OR for Asians was 1.5 (95% CI, 1.28-1.81; P < .0001), compared with the non-Hispanic white population. Other independent risk factors included infection with H pylori (OR, 4.6; 95% CI, 3.8-5.7), smoking history (OR, 1.4; 95% CI, 1.3-1.6), and family history of gastric cancer (OR, 3.4; 95% CI, 2.6-4.4) (all P < .0001). Non-English language was a significant risk factor for gastric cancer in Asians (P = .05). Higher annual median income was associated with reduced risk (OR, 0.84; 95% CI, 0.75-0.95; P = .0004). CONCLUSIONS: In a population study in Southern California, we found racial/ethnic minorities to have a 40%-50% increase in risk of gastric cancer compared with the non-Hispanic white population. In addition to H pylori infection, smoking, family history, and low socioeconomic status were also associated with increased risk. Further characterization of high-risk groups may identify populations appropriate for targeted screening.


Assuntos
Etnicidade , Neoplasias Gástricas/epidemiologia , Idoso , California/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
9.
PLoS One ; 19(5): e0303153, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38771811

RESUMO

BACKGROUND AND AIMS: Population-based screening for gastric cancer (GC) in low prevalence nations is not recommended. The objective of this study was to develop a risk-prediction model to identify high-risk patients who could potentially benefit from targeted screening in a racial/ethnically diverse regional US population. METHODS: We performed a retrospective cohort study from Kaiser Permanente Southern California from January 2008-June 2018 among individuals age ≥50 years. Patients with prior GC or follow-up <30 days were excluded. Censoring occurred at GC, death, age 85 years, disenrollment, end of 5-year follow-up, or study conclusion. Cross-validated LASSO regression models were developed to identify the strongest of 20 candidate predictors (clinical, demographic, and laboratory parameters). Records from 12 of the medical service areas were used for training/initial validation while records from a separate medical service area were used for testing. RESULTS: 1,844,643 individuals formed the study cohort (1,555,392 training and validation, 289,251 testing). Mean age was 61.9 years with 53.3% female. GC incidence was 2.1 (95% CI 2.0-2.2) cases per 10,000 person-years (pyr). Higher incidence was seen with family history: 4.8/10,000 pyr, history of gastric ulcer: 5.3/10,000 pyr, H. pylori: 3.6/10,000 pyr and anemia: 5.3/10,000 pyr. The final model included age, gender, race/ethnicity, smoking, proton-pump inhibitor, family history of gastric cancer, history of gastric ulcer, H. pylori infection, and baseline hemoglobin. The means and standard deviations (SD) of c-index in validation and testing datasets were 0.75 (SD 0.03) and 0.76 (SD 0.02), respectively. CONCLUSIONS: This prediction model may serve as an aid for pre-endoscopic assessment of GC risk for identification of a high-risk population that could benefit from targeted screening.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Medição de Risco/métodos , Detecção Precoce de Câncer , Fatores de Risco , Estados Unidos/epidemiologia , Incidência , Idoso de 80 Anos ou mais , California/epidemiologia
10.
Radiat Oncol ; 19(1): 35, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481285

RESUMO

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DWI) provides a measurement of tumor cellularity. We evaluated the potential of apparent diffusion coefficient (ADC) values obtained from post-external beam radiation therapy (EBRT) DWI and prior to brachytherapy (BT) to predict for complete metabolic response (CMR) in bulky cervical cancer. METHODS: Clinical and DWI (b value = 500 s/mm2) data were obtained from patients undergoing interstitial BT with high-risk clinical target volumes (HR-CTVs) > 30 cc. Volumes were contoured on co-registered T2 weighted images and 90th percentile ADC values were calculated. Patients were stratified by CMR (defined by PET-CT at three months post-BT). Relation of CMR with 90th percentile ADC values and other clinical factors (International Federation of Gynecology and Obstetrics (FIGO) stage, histology, tumor and HR-CTV size, pre-treatment hemoglobin, and age) was assessed both in univariate and multivariate logistic regression analyses. Youden's J statistic was used to identify a threshold value. RESULTS: Among 45 patients, twenty-eight (62%) achieved a CMR. On univariate analysis for CMR, only 90th percentile ADC value was significant (p = 0.029) while other imaging and clinical factors were not. Borderline significant factors were HR-CTV size (p = 0.054) and number of chemotherapy cycles (p = 0.078). On multivariate analysis 90th percentile ADC (p < 0.0001) and HR-CTV size (p < 0.003) were highly significant. Patients with 90th percentile ADC values above 2.10 × 10- 3 mm2/s were 5.33 (95% CI, 1.35-24.4) times more likely to achieve CMR. CONCLUSIONS: Clinical DWI may serve to risk-stratify patients undergoing interstitial BT for bulky cervical cancer.


Assuntos
Braquiterapia , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Braquiterapia/métodos , Imagem de Difusão por Ressonância Magnética/métodos
11.
Mol Pharmacol ; 83(1): 256-66, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23093496

RESUMO

The ADP receptor P2Y(12) belongs to the superfamily of G protein-coupled receptors (GPCRs), and its activation triggers platelet aggregation. Therefore, potent antagonists, such as clopidogrel, are of high clinical relevance in prophylaxis and treatment of thromboembolic events. P2Y(12) displays an elevated basal activity in vitro, and as such, inverse agonists may be therapeutically beneficial compared with antagonists. Only a few inverse agonists of P2Y(12) have been described. To expand this limited chemical space and improve understanding of structural determinants of inverse agonist-receptor interaction, this study screened a purine compound library for lead structures using wild-type (WT) human P2Y(12) and 28 constitutively active mutants. Results showed that ATP and ATP derivatives are agonists at P2Y(12). The potency at P2Y(12) was 2-(methylthio)-ADP > 2-(methylthio)-ATP > ADP > ATP. Determinants required for agonistic ligand activity were identified. Molecular docking studies revealed a binding pocket for the ATP derivatives that is bordered by transmembrane helices 3, 5, 6, and 7 in human P2Y(12,) with Y(105), E(188), R(256), Y(259), and K(280) playing a particularly important role in ligand interaction. N-Methyl-anthraniloyl modification at the 3'-OH of the 2'-deoxyribose leads to ligands (mant-deoxy-ATP [dATP], mant-deoxy-ADP) with inverse agonist activity. Inverse agonist activity of mant-dATP was found at the WT human P2Y(12) and half of the constitutive active P2Y(12) mutants. This study showed that, in addition to ADP and ATP, other ATP derivatives are not only ligands of P2Y(12) but also agonists. Modification of the ribose within ATP can result in inverse activity of ATP-derived ligands.


Assuntos
Simulação de Acoplamento Molecular , Agonistas do Receptor Purinérgico P2Y/química , Purinas/química , Receptores Purinérgicos P2Y12/química , Animais , Células CHO , Células COS , Chlorocebus aethiops , Cricetinae , Cricetulus , AMP Cíclico/metabolismo , Bases de Dados Factuais , Agonismo Inverso de Drogas , Ensaios de Triagem em Larga Escala , Humanos , Ligantes , Mutação , Agonistas do Receptor Purinérgico P2Y/farmacologia , Purinas/farmacologia , Receptores Purinérgicos P2Y12/genética , Receptores Purinérgicos P2Y12/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Relação Estrutura-Atividade
12.
Int J Radiat Oncol Biol Phys ; 116(1): 182-190, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36228745

RESUMO

PURPOSE: Outcomes for patients undergoing chemoradiation for cervical cancer are dependent on adherence to radiation therapy (RT). In other diseases, quality of life (QoL) is associated with treatment adherence, but the association between QoL and RT adherence for patients with cervical cancer remains unclear. METHODS AND MATERIALS: This prospective study included patients undergoing RT for cervical cancer from 2017 to 2021 at an urban safety net hospital. The Functional Assessment of Cancer Therapy-Cervical Cancer Version 4 was used to assess QoL based on 5 subscales (physical, functional, social and emotional, and cervical-cancer specific). The survey was administered at radiation consult, then weekly during RT and at follow-up. Patient information was abstracted from the medical record. Radiation nonadherence was defined as missing ≥2 days of external beam RT. The Functional Assessment of Cancer Therapy-Cervical Cancer Version 4 total and subscale scores were compared between adherent and nonadherent patients. Multivariable logistic regression was performed to control for confounding variables. RESULTS: Ninety-three patients were enrolled, completing 522 surveys. Median age at diagnosis was 46 years (interquartile range, 40-51); 76% of patients were Hispanic, and 12% were Black. Only 30% of patients were nonadherent with RT. A psychiatric comorbidity (P = .012) and symptomatic presentation (P = .027) were associated with decreased adherence. Baseline total QoL was higher in treatment-adherent than in nonadherent patients (median, 124.86; range, 48-160; 108.9, 46-150; P = .01). Higher baseline functional and physical subscale scores were associated with adherence (P < .05). Change from baseline to lowest score during treatment in the emotional subscale was also associated with patient adherence (P < .05). In multivariable analysis, higher baseline physical score, baseline total score, and change in emotional subscale score were associated with adherence (P < .05). CONCLUSIONS: Poor QoL during chemoradiation for cervical cancer is associated with missed treatments. Physician assessment of a patient's well-being while they are undergoing RT is of utmost importance to improve adherence to treatment.


Assuntos
Qualidade de Vida , Neoplasias do Colo do Útero , Feminino , Humanos , Pessoa de Meia-Idade , Emoções , Hispânico ou Latino , Estudos Prospectivos , Qualidade de Vida/psicologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/etnologia , Neoplasias do Colo do Útero/radioterapia , População Urbana , Cooperação e Adesão ao Tratamento , Provedores de Redes de Segurança , Adulto , Negro ou Afro-Americano , Quimiorradioterapia
14.
Clin Transl Gastroenterol ; 13(11): e00531, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36113027

RESUMO

INTRODUCTION: Family history of gastric cancer has been shown as an independent risk factor of gastric cancer development and is associated with increased risk of progression to gastric cancer among patients with gastric intestinal metaplasia (GIM). METHODS: Between 2017 and 2020, we conducted a prospective pilot screening program of patients with a confirmed first-degree relative with gastric cancer to evaluate the feasibility of screening and prevalence of precursor lesions (e.g., GIM or dysplasia) on biopsy. RESULTS: A total of 61 patients completed screening by upper endoscopy with a mapping biopsy protocol: 27 (44%) were found to have GIM and 4 (7%) were found with low-grade dysplasia. DISCUSSION: Our pilot screening program identified a high prevalence of precursor lesions for gastric cancer among asymptomatic patients with a first-degree relative with gastric cancer. Careful endoscopic inspection and standardized biopsy protocols may aid in prompt identification of these precursor lesions in those at risk of gastric cancer.


Assuntos
Prestação Integrada de Cuidados de Saúde , Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Projetos Piloto , Estudos Prospectivos , Detecção Precoce de Câncer , Metaplasia , Gastroscopia/métodos , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/epidemiologia
15.
Transplantation ; 106(12): 2426-2434, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36436102

RESUMO

BACKGROUND: Solid organ transplant recipients (SOTr) are at increased risk for severe disease from coronavirus disease 2019 (COVID-19) compared with non-SOTr. METHODS: We performed a retrospective cohort study between March 1, 2020, and March, 30, 2021, in an integrated healthcare system with 4.3 million members aged ≥18 y including 5126 SOTr. Comparisons in COVID-19 mortality, hospitalization, and incidence were made between SOTr and non-SOTr, and between different SOTr organs. Multivariate analysis was performed to identify risk factors for COVID-19 mortality and hospitalization. RESULTS: There were 600 SOTr (kidney, liver, heart, and lung) with COVID-19. Per person-year incidence of COVID-19 among SOTr was 10.0% versus 7.6% among non-SOTr (P < 0.0001). Compared with uninfected SOTr, infected SOTr were older (57.1 ± 14.0 versus 45.7 ± 17.9 y, P < 0.001), predominantly Hispanic/Latino (58.8% versus 38.6%, P < 0.0001), hypertensive (77.0% versus 23.8%; P < 0.0001), and diabetic (49.6% versus 13.0%; P = 0.0009). Compared with non-SOTr, infected SOTr had higher hospitalization (39.5% versus 6.0%; P < 0.0001), intensive care unit admission (29.1% versus 15.5%; P < 0.0001), and mortality (14.7% versus 1.8%; P < 0.0001) from COVID-19. Older age (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.05-1.10), male gender (HR, 1.79; 95% CI, 1.11-2.86), and higher body mass index (HR, 1.04; 95% CI, 1.00-1.09; P = 0.047) were associated with increased mortality from COVID-19, whereas race, diabetes, and number/type of immunosuppressive medications were not. Among the different SOTr, COVID-19 mortality risk was lowest in liver recipients (HR, 0.34; 95% CI, 0.16-0.73) and highest in lung recipients (HR, 1.74; 95% CI, 0.68-4.42). CONCLUSIONS: SOTr have higher rates of hospitalization and mortality from COVID-19 compared with the general population. Among the SOTr, the incidence and outcomes were distinct among different transplantation types.


Assuntos
COVID-19 , Diabetes Mellitus , Transplante de Órgãos , Humanos , Masculino , Incidência , COVID-19/epidemiologia , Estudos Retrospectivos , Transplante de Órgãos/efeitos adversos , Estudos de Coortes , Fatores de Risco , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia
16.
Clin Transl Gastroenterol ; 13(6): e00478, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35333778

RESUMO

INTRODUCTION: The aim of this study was to assess the feasibility of cross-sectional imaging for detection of pancreatic cancer (PDAC) in patients with new-onset hyperglycemia and diabetes (NOD). METHODS: We conducted a prospective pilot study from November 2018 to March 2020 within an integrated health system. Patients aged 50-85 years with newly elevated glycemic parameters without a history of diabetes were invited to complete a 3-phase contrast-enhanced computed tomography pancreas protocol scan while participating in the Prospective Study to Establish a NOD Cohort. Abnormal pancreatic findings, incidental extrapancreatic findings, and subsequent clinical evaluation were identified. Variability in clinical reporting between medical centers based on descriptors of pancreatic duct and parenchyma was assessed. RESULTS: A total of 130 of 147 participants (88.4%) consented to imaging; 93 scans were completed (before COVID-19 stay-at-home order). The median age was 62.4 years (interquartile range 56.3-68.8), 37.6% women; Hispanic (39.8%), White (29.0%), Black (14.0%), and Asian (13.3%). One (1.1%) case of PDAC (stage IV) was diagnosed, 12 of 93 participants (12.9%) had additional pancreatic findings: 5 fatty infiltration, 3 cysts, 2 atrophy, 1 divisum, and 1 calcification. There were 57 extrapancreatic findings among 52 of 93 (56%) unique patients; 12 of 57 (21.1%) prompted clinical evaluation with 2 additional malignancies diagnosed (nonsmall cell lung and renal oncocytoma). Reports from 1 participating medical center more frequently provided description of pancreatic parenchyma and ducts (92.9% vs 18.4%), P < 0.0001. DISCUSSION: High proportion of incidental findings and variability in clinical reports are challenges to be addressed for a successful NOD-based early detection strategy for PDAC.


Assuntos
COVID-19 , Carcinoma Ductal Pancreático , Diabetes Mellitus , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/patologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Projetos Piloto , Estudos Prospectivos , Neoplasias Pancreáticas
17.
Clin Orthop Relat Res ; 469(10): 2735-43, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21267800

RESUMO

BACKGROUND: Soluble factors released from chondrocytes can both enhance and induce chondrocyte-like behavior in cocultured dedifferentiated cells. The ability to similarly prime and modulate biosynthetic activity of differentiated cells encapsulated in a three-dimensional environment is unknown. QUESTIONS/PURPOSES: To understand the effect of coculture on engineered cartilage, we posed three hypotheses: (1) coculturing with a monolayer of chondrocytes ("chondrocyte feeder layer") expedites and increases engineered tissue growth; (2) expedited growth arises from paracrine effects; and (3) these effects are dependent on the specific morphology and expression of the two-dimensional feeder cells. METHODS: In three separate studies, chondrocyte-laden hydrogels were cocultured with chondrocyte feeder layers. Mechanical properties and biochemical content were quantified to evaluate tissue properties. Histology and immunohistochemistry stains were observed to visualize each constituent's distribution and organization. RESULTS: Coculture with a chondrocyte feeder layer led to stiffer tissue constructs (Young's modulus and dynamic modulus) with greater amounts of glycosaminoglycan and collagen. This was dependent on paracrine signaling between the two populations of cells and was directly modulated by the rounded morphology and expression of the feeder cell monolayer. CONCLUSIONS: These findings suggest a potential need to prime and modulate tissues before implantation and present novel strategies for enhancing medium formulations using soluble factors released by feeder cells. CLINICAL RELEVANCE: Determining the soluble factors present in the coculture system can enhance a chondrogenic medium formulation for improved growth of cartilage substitutes. The feeder layer strategy described here may also be used to prime donor cartilage allografts before implantation to increase their success in vivo.


Assuntos
Cartilagem/metabolismo , Condrócitos/metabolismo , Condrogênese , Engenharia Tecidual/métodos , Animais , Fenômenos Biomecânicos , Cartilagem/transplante , Bovinos , Técnicas de Cultura de Células , Células Cultivadas , Condrócitos/transplante , Técnicas de Cocultura , Colágeno/biossíntese , Módulo de Elasticidade , Glicosaminoglicanos/biossíntese , Hidrogéis , Comunicação Parácrina , Fatores de Tempo , Técnicas de Cultura de Tecidos , Alicerces Teciduais
18.
Clin Transl Gastroenterol ; 11(4): e00147, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32352677

RESUMO

OBJECTIVES: We lack reliable methods for identifying patients with chronic pancreatitis (CP) at increased risk for pancreatic cancer. We aimed to identify radiographic parameters associated with pancreatic cancer in this population. METHODS: We conducted a retrospective cohort study of patients with suspected CP within an integrated healthcare system in Southern California in 2006-2015. Patients were identified by a diagnostic code and confirmed by imaging findings (parenchymal calcification, ductal stones, glandular atrophy, pseudocyst, main duct dilatation, duct irregularity, abnormal side branch, or stricture) defined by the natural language processing of radiographic reports. We used Cox regression to determine the relationship of smoking, alcohol use, acute pancreatitis, diabetes, body mass index, and imaging features with the risk of incident pancreatic cancer at least 1 year after abnormal pancreas imaging. RESULTS: We identified 1,766 patients with a diagnostic code and an imaging feature for CP with a median follow-up of 4.5 years. There were 46 incident pancreatic cancer cases. Factors that predicted incident pancreatic cancer after 1-year of follow-up included obesity (hazard ratio 2.7, 95% confidence interval: 1.2-6.1) and duct dilatation (hazard ratio 10.5, 95% confidence limit: 4.0-27). Five-year incidence of pancreatic cancer in this population with duct dilatation was 6.3%. DISCUSSION: High incidence of pancreatic cancer in suspected patients with CP with pancreatic duct dilatation warrants regular surveillance for pancreatic cancer.


Assuntos
Detecção Precoce de Câncer , Processamento de Linguagem Natural , Pâncreas/diagnóstico por imagem , Neoplasias Pancreáticas/epidemiologia , Pancreatite Crônica/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Seleção de Pacientes , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco/métodos , Tomografia Computadorizada por Raios X
19.
Endosc Int Open ; 7(5): E655-E661, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31058208

RESUMO

Background and aims Current endoscopic methods of biliary decompression in malignant pancreatic neoplasms are often limited by anatomical and technical challenges. In this case series, we report our experience with endoscopic ultrasound (EUS)-guided placement of an electrocautery-enhanced, lumen-apposing self-expandable metallic stent (LAMS) via transmural gallbladder drainage. Methods This is a retrospective case series of nine patients (five male, mean age 63.1 years) who underwent EUS-guided LAMS placement for malignant, obstructive jaundice in the pancreatic head. All nine cases were performed by an experienced interventional endoscopist at a single, tertiary medical center. We review the technical and clinical success rates as well as the incidence of procedural adverse events across the nine patients. Results LAMS placement was technically successful in all cases and there were no procedural adverse events. Seven of nine (77.78 %) patients showed clinical and laboratory improvement immediately following the procedure. One case required re-intervention with interventional radiology guided biliary drain placement. The mean fluoroscopy time was 1.02 minutes. Conclusions EUS-guided LAMS placement for transmural gallbladder drainage in malignant obstruction appears to be a safe and effective technique, allowing patients to proceed to surgery, chemotherapy, or hospice care.

20.
Pancreas ; 48(1): 66-69, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30451795

RESUMO

OBJECTIVES: Distinguishing neuroendocrine tumors (NETs) and other pancreas lesions from adenocarcinomas via endoscopic ultrasound (EUS) requires additional tissue for special staining and processing. Our aim was to determine if main pancreatic duct (PD) diameter on EUS helps to differentiate NET and other unusual tumors from adenocarcinoma. METHODS: We evaluated 30 consecutive patients diagnosed with NET or other pancreas lesions by EUS with 90 matched patients who were found to have adenocarcinoma. Dilated PD was defined as greater than 3 mm. Multivariate logistic regression was used to evaluate associations between lesion type and PD diameter. RESULTS: Among the 30 patients with NET/other pancreas lesions, 21 had NETs, 7 had metastases, and 2 had lymphomas. A dilated PD was demonstrated in only 3.3% of pancreatic NET/other lesions but present in 88.9% of cases of primary adenocarcinoma (P < 0.01). In multivariate analysis, a normal PD diameter and absence of clinical symptoms strongly predicted the presence of pancreatic NET/other versus adenocarcinoma (P < 0.01). CONCLUSIONS: The absence of PD dilation upstream of the lesion suggests NET or other lesions rather than adenocarcinoma. This finding should prompt endosonographers to obtain additional tissue at the time of EUS to send for special studies.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Endossonografia/métodos , Tumores Neuroendócrinos/diagnóstico por imagem , Pâncreas/diagnóstico por imagem , Ductos Pancreáticos/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Adenocarcinoma/diagnóstico , Diagnóstico Diferencial , Humanos , Modelos Logísticos , Análise Multivariada , Tumores Neuroendócrinos/diagnóstico , Pâncreas/patologia , Ductos Pancreáticos/anatomia & histologia , Neoplasias Pancreáticas/diagnóstico , Estudos Prospectivos
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