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1.
Acad Pathol ; 7: 2374289519898857, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31984223

RESUMEN

The transition to a value-based payment system offers pathologists the opportunity to play an increased role in population health by improving outcomes and safety as well as reducing costs. Although laboratory testing itself accounts for a small portion of health-care spending, laboratory data have significant downstream effects in patient management as well as diagnosis. Pathologists currently are heavily engaged in precision medicine, use of laboratory and pathology test results (including autopsy data) to reduce diagnostic errors, and play leading roles in diagnostic management teams. Additionally, pathologists can use aggregate laboratory data to monitor the health of populations and improve health-care outcomes for both individual patients and populations. For the profession to thrive, pathologists will need to focus on extending their roles outside the laboratory beyond the traditional role in the analytic phase of testing. This should include leadership in ensuring correct ordering and interpretation of laboratory testing and leadership in population health programs. Pathologists in training will need to learn key concepts in informatics and data analytics, health-care economics, public health, implementation science, and health systems science. While these changes may reduce reimbursement for the traditional activities of pathologists, new opportunities arise for value creation and new compensation models. This report reviews these opportunities for pathologist leadership in utilization management, precision medicine, reducing diagnostic errors, and improving health-care outcomes.

2.
Acad Pathol ; 5: 2374289518798556, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30327790

RESUMEN

Assessment of physician workloads has become increasingly important in modern academic physician practice, where it is commonly used to allocate resources among departments, to determine staffing, and to set the compensation of individual physicians. The physician work relative value unit system is a frequently used metric in this regard. However, the application of this system to the practice of pathology has proven problematic. One area of uncertainty is the validity of using work relative value unit norms that were derived from general surgical pathology practice to assess the various subspecialties within anatomic pathology. Here, we used data from the 2017 Association of Pathology Chairs practice survey to assess salary and work relative value unit data for single-subspecialty practitioners in US academic pathology departments in the prior year (2016). Five subspecialties were evaluated: dermatopathology, gastrointestinal pathology, hematopathology/hematology, renal pathology, and neuropathology. Data for general surgical pathologists and cytopathologists were included for comparison. For this analysis, survey data were available for 168 practitioners in 43 US academic departments of pathology. Salary ranges varied little among subspecialties, with the exception of dermatopathology, where salaries were higher. In contrast, work relative value unit productivity varied widely among different subspecialties, with median values differing as much as 4- to 7-fold between subspecialties. These results suggest that the use of a single overall work relative value unit standard is not appropriate for specialty- or subspecialty-based anatomic pathology practice, and that either the benchmark norms should be tailored to individual practice patterns, or an alternative system of workload measurement should be developed.

3.
Arch Pathol Lab Med ; 142(6): 693-695, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29848032

RESUMEN

CONTEXT: - Types 16 and 18 are the most widely studied high-risk types of human papillomavirus (HPV). However, other high-risk HPV types (HPV non-16/18) also play a significant role in cervical neoplasia. Currently, screening and management algorithms separate out HPV 16/18 from all other HPV non-16/18 types. In addition, most of the previously vaccinated population has only been vaccinated for these high-risk types, so many women are still vulnerable to HPV non-16/18 infections. OBJECTIVE: - To review the prevalence and role of HPV non-16/18 neoplasia and to review current surveillance, management, and vaccination strategies in view of these findings. DATA SOURCES: - The study comprised a review of the literature. CONCLUSIONS: - Although HPV non-16/18 types are less frequently associated with cervical intraepithelial neoplasia and cancer, they are nonetheless a significant cause of disease. Further stratification of higher-risk HPV non-16/18 may be necessary to improve prevention and management, however, regional prevalence differences may make a unified approach difficult. As HPV 16/18 infections decrease owing to vaccination of at-risk women, the relative frequency of HPV non-16/18 will increase, although the latest vaccine covers several more high-risk types.


Asunto(s)
Papillomaviridae/inmunología , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus , Displasia del Cuello del Útero/prevención & control , Neoplasias del Cuello Uterino/prevención & control , Vacunación , Monitoreo Epidemiológico , Femenino , Humanos , Tamizaje Masivo , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Prevalencia , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/virología
5.
Arch Pathol Lab Med ; 142(6): 715-718, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29848036

RESUMEN

CONTEXT: - Human papillomavirus (HPV) is implicated in the development of oropharyngeal squamous cell carcinomas (OPC), particularly those cancers developing in tonsillar tissue. OBJECTIVES: - To review the prevalence, subtypes, and methods of detecting HPV in OPC and to review the epidemiology, histology, staging, management, and prevention of these cancers. DATA SOURCES: - The study comprised a review of the literature. CONCLUSIONS: - The incidence of HPV-OPC is rising globally and in the United States, but rates of HPV-positivity vary with the anatomic site(s) and the population studied, as well as the method of detecting HPV infection. These tumors are more common in men. In contrast to HPV- OPC, the rates of smoking and alcohol abuse are lower. The HPV 16 subtype is predominant, and immunohistochemistry staining for p16 and in situ hybridization are the most widely used methods clinically to detect transcriptionally active HPV. Moreover, HPV-OPC has a unique tumor phenotype with predominantly nonkeratinizing morphology and a variety of patterns. These cancers often present with cystic lymph node metastases. The prognosis for HPV-OPC is significantly better than HPV- OPC and has led to differences in grading, staging, and management. Although there are similarities to cervical cancer, there are challenges in preventing such cancers.


Asunto(s)
Neoplasias Orofaríngeas/virología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/virología , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Femenino , Papillomavirus Humano 16/aislamiento & purificación , Humanos , Inmunohistoquímica , Hibridación in Situ , Incidencia , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/prevención & control , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/prevención & control , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/prevención & control
6.
J Appl Physiol (1985) ; 124(3): 573-582, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-29097631

RESUMEN

Proponents for electronic cigarettes (E-cigs) claim that they are a safe alternative to tobacco-based cigarettes; however, little is known about the long-term effects of exposure to E-cig vapor on vascular function. The purpose of this study was to determine the cardiovascular consequences of chronic E-cig exposure. Female mice (C57BL/6 background strain) were randomly assigned to chronic daily exposure to E-cig vapor, standard (3R4F reference) cigarette smoke, or filtered air ( n = 15/group). Respective whole body exposures consisted of four 1-h-exposure time blocks, separated by 30-min intervals of fresh air breaks, resulting in intermittent daily exposure for a total of 4 h/day, 5 days/wk for 8 mo. Noninvasive ultrasonography was used to assess cardiac function and aortic arterial stiffness (AS), measured as pulse wave velocity, at three times points (before, during, and after chronic exposure). Upon completion of the 8-mo exposure, ex vivo wire tension myography and force transduction were used to measure changes in thoracic aortic tension in response to vasoactive-inducing compounds. AS increased 2.5- and 2.8-fold in E-cig- and 3R4F-exposed mice, respectively, compared with air-exposed control mice ( P < 0.05). The maximal aortic relaxation to methacholine was 24% and 33% lower in E-cig- and 3R4F-exposed mice, respectively, than in controls ( P < 0.05). No differences were noted in sodium nitroprusside dilation between the groups. 3R4F exposure altered cardiac function by reducing fractional shortening and ejection fraction after 8 mo ( P < 0.05). A similar, although not statistically significant, tendency was also observed with E-cig exposure ( P < 0.10). Histological and respiratory function data support emphysema-associated changes in 3R4F-exposed, but not E-cig-exposed, mice. Chronic exposure to E-cig vapor accelerates AS, significantly impairs aortic endothelial function, and may lead to impaired cardiac function. The clinical implication from this study is that chronic use of E-cigs, even at relatively low exposure levels, induces cardiovascular dysfunction. NEW & NOTEWORTHY Electronic cigarettes (E-cigs) are marketed as safe, but there has been insufficient long-term exposure to humans to justify these claims. This is the first study to report the long-term in vivo vascular consequences of 8 mo of exposure to E-cig vapor in mice (equivalent to ~25 yr of exposure in humans). We report that E-cig exposure increases arterial stiffness and impairs normal vascular reactivity responses, similar to other risk factors, including cigarette smoking, which contribute to the development of cardiovascular disease.


Asunto(s)
Enfermedades Cardiovasculares/etiología , Vapeo/efectos adversos , Animales , Ecocardiografía , Sistemas Electrónicos de Liberación de Nicotina , Femenino , Ratones , Ratones Endogámicos C57BL , Análisis de la Onda del Pulso , Distribución Aleatoria , Pruebas de Función Respiratoria , Rigidez Vascular
7.
Acad Pathol ; 4: 2374289517707506, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28725791

RESUMEN

Laboratory data are critical to analyzing and improving clinical quality. In the setting of residual use of creatine kinase M and B isoenzyme testing for myocardial infarction, we assessed disease outcomes of discordant creatine kinase M and B isoenzyme +/troponin I (-) test pairs in order to address anticipated clinician concerns about potential loss of case-finding sensitivity following proposed discontinuation of routine creatine kinase and creatine kinase M and B isoenzyme testing. Time-sequenced interventions were introduced. The main outcome was the percentage of cardiac marker studies performed within guidelines. Nonguideline orders dominated at baseline. Creatine kinase M and B isoenzyme testing in 7496 order sets failed to detect additional myocardial infarctions but was associated with 42 potentially preventable admissions/quarter. Interruptive computerized soft stops improved guideline compliance from 32.3% to 58% (P < .001) in services not receiving peer leader intervention and to >80% (P < .001) with peer leadership that featured dashboard feedback about test order performance. This successful experience was recapitulated in interrupted time series within 2 additional services within facility 1 and then in 2 external hospitals (including a critical access facility). Improvements have been sustained postintervention. Laboratory cost savings at the academic facility were estimated to be ≥US$635 000 per year. National collaborative data indicated that facility 1 improved its order patterns from fourth to first quartile compared to peer norms and imply that nonguideline orders persist elsewhere. This example illustrates how pathologists can provide leadership in assisting clinicians in changing laboratory ordering practices. We found that clinicians respond to local laboratory data about their own test performance and that evidence suggesting harm is more compelling to clinicians than evidence of cost savings. Our experience indicates that interventions done at an academic facility can be readily instituted by private practitioners at external facilities. The intervention data also supplement existing literature that electronic order interruptions are more successful when combined with modalities that rely on peer education combined with dashboard feedback about laboratory order performance. The findings may have implications for the role of the pathology laboratory in the ongoing pivot from quantity-based to value-based health care.

8.
Acad Pathol ; 3: 2374289516666832, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-28725777

RESUMEN

The most common benchmarks for faculty productivity are derived from Medical Group Management Association (MGMA) or Vizient-AAMC Faculty Practice Solutions Center® (FPSC) databases. The Association of Pathology Chairs has also collected similar survey data for several years. We examined the Association of Pathology Chairs annual faculty productivity data and compared it with MGMA and FPSC data to understand the value, inherent flaws, and limitations of benchmarking data. We hypothesized that the variability in calculated faculty productivity is due to the type of practice model and clinical effort allocation. Data from the Association of Pathology Chairs survey on 629 surgical pathologists and/or anatomic pathologists from 51 programs were analyzed. From review of service assignments, we were able to assign each pathologist to a specific practice model: general anatomic pathologists/surgical pathologists, 1 or more subspecialties, or a hybrid of the 2 models. There were statistically significant differences among academic ranks and practice types. When we analyzed our data using each organization's methods, the median results for the anatomic pathologists/surgical pathologists general practice model compared to MGMA and FPSC results for anatomic and/or surgical pathology were quite close. Both MGMA and FPSC data exclude a significant proportion of academic pathologists with clinical duties. We used the more inclusive FPSC definition of clinical "full-time faculty" (0.60 clinical full-time equivalent and above). The correlation between clinical full-time equivalent effort allocation, annual days on service, and annual work relative value unit productivity was poor. This study demonstrates that effort allocations are variable across academic departments of pathology and do not correlate well with either work relative value unit effort or reported days on service. Although the Association of Pathology Chairs-reported median work relative value unit productivity approximated MGMA and FPSC benchmark data, we conclude that more rigorous standardization of academic faculty effort assignment will be needed to improve the value of work relative value unit measurements of faculty productivity.

9.
Acad Pathol ; 3: 2374289516679849, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-28725782

RESUMEN

We investigated the influence of pathology data to improve patient outcomes in the treatment of high-grade cervical neoplasia in a joint pathology and gynecology collaboration. Two of us (B.S.D. and M.D.) reviewed all cytology, colposcopy and surgical pathology results, patient history, and pregnancy outcomes from all patients with loop electrosurgical excision procedure specimens for a 33-month period (January 2011-September 2013). We used this to determine compliance to 2006 consensus guidelines for the performance of loop electrosurgical excision procedure and shared this information in 2 interprofessional and interdisciplinary educational interventions with Obstetrics/Gynecology and Pathology faculty at the end of September 2013. We simultaneously emphasized the new 2013 guidelines. During the postintervention period, we continued to provide follow-up using the parameters previously collected. Our postintervention data include 90 cases from a 27-month period (October 2013-December 2015). Our preintervention data include 331 cases in 33 months (average 10.0 per month) with 76% adherence to guidelines. Postintervention, there were 90 cases in 27 months (average 3.4 per month) and 96% adherence to the 2013 (more conservative) guidelines (P < .0001, χ2 test). Preintervention, the rate of high-grade squamous intraepithelial lesion in loop electrosurgical excision procedures was 44%, whereas postintervention, there was a 60% high-grade squamous intraepithelial lesion rate on loop electrosurgical excision procedure (P < .0087 by 2-tailed Fisher exact test). The duration between diagnosis of low-grade squamous intraepithelial lesion and loop electrosurgical excision procedure also increased significantly from a median 25.5 months preintervention to 54 months postintervention (P < .0073; Wilcoxon Kruskal-Wallis test). Postintervention, there was a marked decrease of loop electrosurgical excision procedure cases as well as better patient outcomes. We infer improved patient safety, and higher value can be achieved by providing performance-based pathologic data.

10.
Am J Otolaryngol ; 36(2): 259-63, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25523505

RESUMEN

PURPOSE: 1) To determine SUVs and PET/CT characteristics of Warthin's tumors in patients presenting to a head and neck cancer clinic. 2) To analyze the impact of PET/CT on the clinical course of these patients. MATERIALS AND METHODS: This is a single-institution retrospective analysis of patients with proven Warthin's tumors who underwent PET/CT done at or near the time of diagnosis and presented to a head and neck cancer practice. Data were obtained from the electronic medical records of these patients and the imaging and pathology databases. RESULTS: Six patients with Warthin's tumor met the criteria for and form the study cohort. Three patients had bilateral tumors. The SUVs for Warthin's varied from 3.4 to 16.1 in these patients, with an average of 7.8 and these SUVs were higher for Warthin's than for the cancers. These findings on PET/CT in this group required additional workup of all patients and required FNA, surgery or SPECT-CT to confirm the diagnosis. CONCLUSION: Although it is known that Warthin's tumor may be hypermetabolic on PET, this finding in the parotid or neck on PET/CT alters the evaluation and treatment of head and neck cancer patients and patients with cancers outside the head and neck by raising the concern about metastatic disease or multiple primary cancers. In other patients, PET/CT obtained for other reasons may prompt concern about incidental malignancy. This series specifically characterizes clinical features, SPECT-CT and FNA findings that can help reinforce the diagnosis of Warthin's and facilitate management.


Asunto(s)
Adenolinfoma/diagnóstico por imagen , Adenolinfoma/patología , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/patología , Tomografía de Emisión de Positrones/métodos , Adenolinfoma/diagnóstico , Anciano , Anciano de 80 o más Años , Biopsia con Aguja Fina/métodos , Bases de Datos Factuales , Diagnóstico Diferencial , Femenino , Fluorodesoxiglucosa F18 , Neoplasias de Cabeza y Cuello/diagnóstico , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Neoplasias de la Parótida/diagnóstico por imagen , Neoplasias de la Parótida/patología , Estudios Retrospectivos , Medición de Riesgo , Tomografía Computarizada de Emisión de Fotón Único/métodos , Tomografía Computarizada por Rayos X/métodos
11.
Arch Pathol Lab Med ; 135(11): 1442-6, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22032572

RESUMEN

CONTEXT: In 2006, the first gynecologic cytology proficiency tests were offered by the College of American Pathologists. Four years of data are now available using field-validated slides, including conventional and liquid-based Papanicolaou tests. OBJECTIVE: To characterize the pattern of error types that resulted in initial proficiency-test failure for cytotechnologists, primary screening pathologists, and secondary pathologists (those whose slides are prescreened by cytotechnologists). DESIGN: The results of 37 029 initial College of American Pathologists Papanicolaou proficiency tests were reviewed from 4 slide-set modules: conventional, ThinPrep, SurePath, or a module containing all 3 slide types. RESULTS: During this 4-year period, cytotechnologists were least likely to fail the initial test (3.4%; 614 of 18 264), followed by secondary pathologists (ie, those reviewing slides already screened by a cytotechnologist) with a failure rate of 4.2% (728 of 17 346), and primary pathologists (ie, those screening their own slides) having the highest level of failure (13.7%; 194 of 1419). Failure rates have fallen for all 3 groups over time. Pathologists are graded more stringently on proficiency tests, and more primary pathologists would have passed if they had been graded as cytotechnologists. There were no significant differences among performances using different types of slide sets. False-positive errors were common for both primary (63.9%; 124 of 194 errors) and secondary (55.6%; 405 of 728 errors) pathologists, whereas automatic failures were most common for cytotechnologists (75.7%; 465 of 614 errors). CONCLUSIONS: The failure rate is decreasing for all participants. The failures for primary pathologist screeners are due to false-positive responses. Primary screening cytotechnologists and secondary pathologists have automatic failures more often than do primary screening pathologists.


Asunto(s)
Citodiagnóstico/normas , Evaluación Educacional/métodos , Patología Clínica/educación , Patología Clínica/normas , Garantía de la Calidad de Atención de Salud , Errores Diagnósticos/prevención & control , Femenino , Humanos , Prueba de Papanicolaou , Reproducibilidad de los Resultados , Neoplasias del Cuello Uterino/diagnóstico , Frotis Vaginal/normas , Displasia del Cuello del Útero/diagnóstico
12.
J Occup Environ Med ; 51(2): 164-9, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19209037

RESUMEN

OBJECTIVES: To investigate evidence that lymph node silicosis can precede parenchymal silicosis. METHODS: The study population was comprised of 264 deceased male uranium miners for whom two or more of four pathologists agreed on the presence or absence of silicosis in lymph nodes and lung parenchyma. We had work histories and silica exposure estimates. RESULTS: Twenty percent of the miners had lymph node silicosis only, 4% had parenchymal silicosis only, and 39% had both. Silica exposure was lower for miners with lymph node silicosis only than for those with both lymph node and parenchymal silicosis. Lymph node silicosis was associated with parenchymal silicosis after adjustment for silica exposure. CONCLUSIONS: Our results are consistent with silicosis potentially occurring in lymph nodes before the parenchyma. Lymph node damage could impair silica clearance and increase the risk for parenchymal silicosis.


Asunto(s)
Ganglios Linfáticos/patología , Minería , Exposición Profesional/efectos adversos , Silicosis/patología , Uranio , Cadáver , Alemania/epidemiología , Humanos , Masculino , Silicosis/epidemiología , Silicosis/etiología
13.
J Grad Med Educ ; 1(1): 37-44, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21975705

RESUMEN

OBJECTIVES: To determine whether a longitudinal, case-based evaluation system can predict acquisition of competency in surgical pathology and how trainees at risk can be identified early. DESIGN: Data were collected for trainee performance on surgical pathology cases (how well their diagnosis agreed with the faculty diagnosis) and compared with training outcomes. Negative training outcomes included failure to complete the residency, failure to pass the anatomic pathology component of the American Board of Pathology examination, and/or failure to obtain or hold a position immediately following training. FINDINGS: Thirty-three trainees recorded diagnoses for 54 326 surgical pathology cases, with outcome data available for 15 residents. Mean case-based performance was significantly higher for those with positive outcomes, and outcome status could be predicted as early as postgraduate year-1 (P  =  .0001). Performance on the first postgraduate year-1 rotation was significantly associated with the outcome (P  =  .02). Although trainees with unsuccessful outcomes improved their performance more rapidly, they started below residents with successful outcomes and did not make up the difference during training. There was no significant difference in Step 1 or 2 United States Medical Licensing Examination (USMLE) scores when compared with performance or final outcomes (P  =  .43 and P  =  .68, respectively) and the resident in-service examination (RISE) had limited predictive ability. DISCUSSION: Differences between successful- and unsuccessful-outcome residents were most evident in early residency, ideal for designing interventions or counseling residents to consider another specialty. CONCLUSION: Our longitudinal case-based system successfully identified trainees at risk for failure to acquire critical competencies for surgical pathology early in the program.

14.
Arch Pathol Lab Med ; 132(11): 1716-8, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18976004

RESUMEN

CONTEXT: Newer liquid-based preparations differ morphologically from classic preparations (smears, filters, and cytocentrifuged preparations). Is adenocarcinoma more readily detected in liquid-based preparations? We reviewed responses from 16,750 fluid challenges of adenocarcinoma distributed in 2005 in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology (CAP NGC). OBJECTIVE: To compare the performance of body cavity fluid liquid-based preparations with adenocarcinoma to that in classic preparations in the CAP NGC. DESIGN: Responses for ThinPrep challenges were compared with classic preparations for exact match diagnoses of adenocarcinoma from pelvic washes, pleural fluid, pericardial fluid, and peritoneal fluids in the 2005 CAP NGC. RESULTS: A total of 13,690 pathologists, 8345 cytotechnologists, and 5958 laboratories submitted responses to fluid challenges in 2005. Adenocarcinoma comprised 16,750 of the fluid challenges; 88% were classic preparations, and 12% were ThinPrep challenges. The exact match to the reference diagnosis of adenocarcinoma was seen in 77% of conventional preparations and 81% of ThinPrep challenges when a general category of "positive for malignancy" was assigned. When "suspicious for malignancy," an exact match diagnosis of adenocarcinoma was made in 5% and 4% of classic and ThinPrep challenges, respectively. CONCLUSIONS: ThinPrep challenges performed slightly better overall, but only pelvic washings and peritoneal fluids demonstrated statistically significant improved performance with ThinPrep challenges. Use of liquid-based preparation is widespread for nongynecologic preparations and performs as well, and sometimes better than, classic preparations in an interlaboratory comparison program.


Asunto(s)
Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Líquidos Corporales/citología , Microtomía , Patología Clínica/métodos , Humanos , Estudios Retrospectivos , Sociedades Médicas , Estados Unidos
15.
Environ Health Perspect ; 116(9): 1211-7, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18795165

RESUMEN

BACKGROUND: Single-wall carbon nanotubes (SWCNTs), with their unique physicochemical and mechanical properties, have many potential new applications in medicine and industry. There has been great concern subsequent to preliminary investigations of the toxicity, biopersistence, pathogenicity, and ability of SWCNTs to translocate to subpleural areas. These results compel studies of potential interactions of SWCNTs with mesothelial cells. OBJECTIVE: Exposure to asbestos is the primary cause of malignant mesothelioma in 80-90% of individuals who develop the disease. Because the mesothelial cells are the primary target cells of asbestos-induced molecular changes mediated through an oxidant-linked mechanism, we used normal mesothelial and malignant mesothelial cells to investigate alterations in molecular signaling in response to a commercially manufactured SWCNT. METHODS: In the present study, we exposed mesothelial cells to SWCNTs and investigated reactive oxygen species (ROS) generation, cell viability, DNA damage, histone H2AX phosphorylation, activation of poly(ADP-ribose) polymerase 1 (PARP-1), stimulation of extracellular signal-regulated kinase (ERKs), Jun N-terminal kinases (JNKs), protein p38, and activation of activator protein-1 (AP-1), nuclear factor kappaB (NF-kappaB), and protein serine-threonine kinase (Akt). RESULTS: Exposure to SWCNTs induced ROS generation, increased cell death, enhanced DNA damage and H2AX phosphorylation, and activated PARP, AP-1, NF-kappaB, p38, and Akt in a dose-dependent manner. These events recapitulate some of the key molecular events involved in mesothelioma development associated with asbestos exposure. CONCLUSIONS: The cellular and molecular findings reported here do suggest that SWCNTs can cause potentially adverse cellular responses in mesothelial cells through activation of molecular signaling associated with oxidative stress, which is of sufficient significance to warrant in vivo animal exposure studies.


Asunto(s)
Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Nanotubos de Carbono , Neoplasias Mesoteliales/metabolismo , Estrés Oxidativo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor de Transcripción AP-1/metabolismo , Western Blotting , Ensayo Cometa , Daño del ADN , Activación Enzimática , Histonas/metabolismo , Humanos , Neoplasias Mesoteliales/enzimología , Neoplasias Mesoteliales/patología , Fosforilación , Especies Reactivas de Oxígeno/metabolismo , Células Tumorales Cultivadas
16.
J Cutan Pathol ; 33 Suppl 2: 24-8, 2006 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16972949

RESUMEN

Atypical fibroxanthoma (AFX), a benign lesion, and pleomorphic malignant fibrous histiocytoma (MFH) are thought to represent points along the same neoplastic spectrum but with different prognoses and treatments. Diagnosis based on histology and clinical parameters alone is sometimes difficult, and a reliable cost-effective immunohistochemical marker to help distinguish these lesions would be beneficial. The diagnosis of AFX or MFH was based upon published clinical and microscopic criteria. Formalin-fixed, paraffin-embedded tissues of 17 cases of AFX and 26 cases of MFH were immunostained with monoclonal antibody to CD99. For all cases, CD99 expression was scored on a four-tiered scale: negative, weak (1+), moderate (2+), or strong (3+). Two pathologists blinded to tumor diagnoses and type of immunostain evaluated each case independently. The interobserver correlation coefficient was calculated. Seventeen patients with AFX (16 males and one female; mean age = 79) and 26 patients with MFH (16 males and 10 females; mean age = 60) were included. AFX lesions were from the head and the face, mean size = 1.5 cm, and MFH lesions were from the head, the neck, the trunk, and the upper/lower extremities, mean size = 5.2 cm. The 17 cases of AFX demonstrated moderate or strong (2 to 3+) immunoreactivity with CD99, compared to nine of 26 (35%) MFH cases (chi-square = 18.38; p < 0.001; interobserver correlation coefficient = 0.83). Of these, 16 of 17 (94%) AFX cases stained diffusely with CD99, while only four of 26 (15%) MFH cases stained diffusely. Control slides were adequate. Our study demonstrated that CD99 can help distinguish AFX from MFH, in addition to other immunohistochemistry as well as clinical and histologic criteria.


Asunto(s)
Antígenos CD/biosíntesis , Biomarcadores de Tumor/biosíntesis , Moléculas de Adhesión Celular/biosíntesis , Fibroma/metabolismo , Fibroma/patología , Regulación Neoplásica de la Expresión Génica , Histiocitoma Fibroso Maligno/metabolismo , Histiocitoma Fibroso Maligno/patología , Xantomatosis/metabolismo , Xantomatosis/patología , Antígeno 12E7 , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/inmunología , Biomarcadores de Tumor/inmunología , Moléculas de Adhesión Celular/inmunología , Diagnóstico Diferencial , Femenino , Fibroma/inmunología , Histiocitoma Fibroso Maligno/inmunología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Xantomatosis/inmunología
17.
Arch Pathol Lab Med ; 130(2): 188-93, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16454560

RESUMEN

CONTEXT: Accreditation Council for Graduate Medical Education guidelines require the evaluation of residents in 6 competencies. Pathology residents demonstrate medical knowledge, patient care, communication, and practice-based learning competencies in their attainment of competency in surgical pathology diagnosis. OBJECTIVE: To implement a prospective case-based approach to longitudinally evaluate the acquisition of competency in surgical pathology diagnosis by trainees. DESIGN: Each resident made his or her surgical pathology diagnosis on cases before faculty review of the cases. Faculty members scored each resident diagnosis as to whether they agree, partially agree, or disagree with the diagnosis. Forty-three months of surgical pathology reports (August 2001 through January 2005) and 22,252 surgical pathology cases were analyzed. SETTING: Pathology residency program. PARTICIPANTS: Thirteen faculty members and 21 trainees. MAIN OUTCOME MEASURE: Time and training year trends for the number of cases reviewed and the percent agreement between faculty and trainees on the diagnoses. RESULTS: A mean of 146 cases (range, 12-327 cases) was reviewed during each month-long rotation. The number of cases reviewed increased through postgraduate year 4. The percent agreement on the diagnoses was 78% (range, 56%- 99%) for all trainees, with improvement by postgraduate year, although the improvement attenuated by postgraduate year 3. Residents were less likely to preview the most complex cases. Faculty rank and sex and resident sex did not significantly affect outcomes. The overall agreement on the diagnoses increased over time. Residents experiencing difficulty could be identified clearly and early. CONCLUSIONS: Individual resident performance was easily tracked over time. The review of hundreds of reports increases systems accountability and allows more objectivity than traditional evaluations. The use of case-based evaluation fosters earlier identification and remediation of deficiencies.


Asunto(s)
Manejo de Caso/normas , Competencia Clínica/normas , Educación Basada en Competencias , Internado y Residencia/normas , Patología Quirúrgica , Manejo de Caso/estadística & datos numéricos , Competencia Clínica/estadística & datos numéricos , Educación , Evaluación Educacional , Docentes Médicos , Humanos , Internado y Residencia/estadística & datos numéricos , Patología Quirúrgica/educación , Patología Quirúrgica/normas , Patología Quirúrgica/estadística & datos numéricos , Estudios Prospectivos
20.
Mol Cancer ; 2: 21, 2003 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-12713669

RESUMEN

BACKGROUND: The CCAAT element binding protein family of transcriptional factors consists of at least six members of the basic leucine zipper DNA binding proteins that bind to the same CCAAT palindromic DNA sequence through homo- or hetero-dimerization with the same family members. C/EBP beta has been shown to play an important role in mediating the effects of the LH/hCG in ovarian development. C/EBP beta was also found increased in ovarian cancer and correlated to ovarian cancer progression. DESIGN: We assessed the C/EBP beta expression pattern in the normal and neoplastic conditions of the female genital tract by immunostaining the normal cervix--10 cases, squamous intraepithelial lesion (SIL)-10, invasive squamous carcinomas of cervix--10 cases, normal endometrial tissue--10 cases, and invasive endometrial adenocarcinomas carcinomas-10 cases. The staining pattern and intensity were graded from 0 to 2+. Results were statistically analyzed utilizing JMP 4.1. RESULTS: C/EPB beta expression was detected in the normal proliferative squamous, dysplastic and malignant squamous epithelial cells. There was no statistical correlation between C/EPB beta staining in benign squamous, endocervical tissue, SIL, and squamous cancer, as the majority of all stained positively (91%, 79%, 71% and 89%, respectively, p = 0.3448). However, endometrial carcinoma was significantly more likely to stain positively with C/EPB beta than benign endometrial glands (92% versus 3% respectively, p < 0.0001, Fisher's exact test). CONCLUSION: C/EBP beta is more likely to be preferentially expressed in endometrial adenocarcinoma as compared to benign endometrial tissue. There is no difference of C/EPB beta expression in squamous neoplasia of the cervix.


Asunto(s)
Proteína beta Potenciadora de Unión a CCAAT/biosíntesis , Endometrio/patología , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Cuello del Útero/química , Cuello del Útero/patología , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Endometrio/química , Femenino , Humanos , Inmunohistoquímica , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología
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