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1.
Artículo en Inglés | MEDLINE | ID: mdl-36718059

RESUMEN

BACKGROUND: Lymphocytic esophagitis (LE) is a poorly understood clinical finding that has been increasingly identified in the last decade. Previous studies proposed increased frequency of LE in elderly females, as well as associations with smoking and pediatric Crohn's disease. OBJECTIVE: We aimed to determine the patient characteristics and clinical features of our adult LE patients. As inflammation in the esophagus has been linked to cancer, this review also describes this association. However, there are no reported cases of malignant transformation in those with underlying lymphocytic esophagitis. METHODS: We retrospectively reviewed records for patients at the University of Missouri Hospital- Columbia (located in the USA) who had a histopathological diagnosis of LE. Cases of LE were identified using the pathology reporting system at the University of Missouri Hospital for esophageal biopsy specimens for the above-mentioned period. RESULTS: The data of a total of 20 adult cases with esophageal biopsy specimens consistent with LE were included. CONCLUSION: LE seems to be a benign but disturbing clinical problem and should be remembered in elderly females complaining of dysphagia or refractory reflux symptoms. It has similar endoscopic findings of eosinophilic esophagitis with rings and esophagitis. Smoking and hiatal hernia are common risk factors. The majority of LE patients can respond to proton pump inhibitor (PPI) therapy. Endoscopic dilations and steroid therapy should be considered for PPI nonresponder LE patients.


Asunto(s)
Trastornos de Deglución , Esofagitis Eosinofílica , Adulto , Femenino , Niño , Humanos , Anciano , Estudios Retrospectivos , Esofagitis Eosinofílica/diagnóstico , Trastornos de Deglución/epidemiología , Linfocitos/patología
2.
J Pathol Inform ; 12: 26, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34447606

RESUMEN

BACKGROUND: Cervical intraepithelial neoplasia (CIN) is regarded as a potential precancerous state of the uterine cervix. Timely and appropriate early treatment of CIN can help reduce cervical cancer mortality. Accurate estimation of CIN grade correlated with human papillomavirus type, which is the primary cause of the disease, helps determine the patient's risk for developing the disease. Colposcopy is used to select women for biopsy. Expert pathologists examine the biopsied cervical epithelial tissue under a microscope. The examination can take a long time and is prone to error and often results in high inter-and intra-observer variability in outcomes. METHODOLOGY: We propose a novel image analysis toolbox that can automate CIN diagnosis using whole slide image (digitized biopsies) of cervical tissue samples. The toolbox is built as a four-step deep learning model that detects the epithelium regions, segments the detected epithelial portions, analyzes local vertical segment regions, and finally classifies each epithelium block with localized attention. We propose an epithelium detection network in this study and make use of our earlier research on epithelium segmentation and CIN classification to complete the design of the end-to-end CIN diagnosis toolbox. RESULTS: The results show that automated epithelium detection and segmentation for CIN classification yields comparable results to manually segmented epithelium CIN classification. CONCLUSION: This highlights the potential as a tool for automated digitized histology slide image analysis to assist expert pathologists.

3.
J Pathol Inform ; 11: 10, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32477616

RESUMEN

BACKGROUND: Automated pathology techniques for detecting cervical cancer at the premalignant stage have advantages for women in areas with limited medical resources. METHODS: This article presents EpithNet, a deep learning approach for the critical step of automated epithelium segmentation in digitized cervical histology images. EpithNet employs three regression networks of varying dimensions of image input blocks (patches) surrounding a given pixel, with all blocks at a fixed resolution, using varying network depth. RESULTS: The proposed model was evaluated on 311 digitized histology epithelial images and the results indicate that the technique maximizes region-based information to improve pixel-wise probability estimates. EpithNet-mc model, formed by intermediate concatenation of the convolutional layers of the three models, was observed to achieve 94% Jaccard index (intersection over union) which is 26.4% higher than the benchmark model. CONCLUSIONS: EpithNet yields better epithelial segmentation results than state-of-the-art benchmark methods.

4.
J Pathol Inform ; 11: 4, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32166042

RESUMEN

BACKGROUND: Free-text sections of pathology reports contain the most important information from a diagnostic standpoint. However, this information is largely underutilized for computer-based analytics. The vast majority of NLP-based methods lack a capacity to accurately extract complex diagnostic entities and relationships among them as well as to provide an adequate knowledge representation for downstream data-mining applications. METHODS: In this paper, we introduce a novel informatics pipeline that extends open information extraction (openIE) techniques with artificial intelligence (AI) based modeling to extract and transform complex diagnostic entities and relationships among them into Knowledge Graphs (KGs) of relational triples (RTs). RESULTS: Evaluation studies have demonstrated that the pipeline's output significantly differs from a random process. The semantic similarity with original reports is high (Mean Weighted Overlap of 0.83). The precision and recall of extracted RTs based on experts' assessment were 0.925 and 0.841 respectively (P <0.0001). Inter-rater agreement was significant at 93.6% and inter-rated reliability was 81.8%. CONCLUSION: The results demonstrated important properties of the pipeline such as high accuracy, minimality and adequate knowledge representation. Therefore, we conclude that the pipeline can be used in various downstream data-mining applications to assist diagnostic medicine.

5.
J Pathol Inform ; 11: 40, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33828898

RESUMEN

BACKGROUND: Cervical cancer is one of the deadliest cancers affecting women globally. Cervical intraepithelial neoplasia (CIN) assessment using histopathological examination of cervical biopsy slides is subject to interobserver variability. Automated processing of digitized histopathology slides has the potential for more accurate classification for CIN grades from normal to increasing grades of pre-malignancy: CIN1, CIN2, and CIN3. METHODOLOGY: Cervix disease is generally understood to progress from the bottom (basement membrane) to the top of the epithelium. To model this relationship of disease severity to spatial distribution of abnormalities, we propose a network pipeline, DeepCIN, to analyze high-resolution epithelium images (manually extracted from whole-slide images) hierarchically by focusing on localized vertical regions and fusing this local information for determining Normal/CIN classification. The pipeline contains two classifier networks: (1) a cross-sectional, vertical segment-level sequence generator is trained using weak supervision to generate feature sequences from the vertical segments to preserve the bottom-to-top feature relationships in the epithelium image data and (2) an attention-based fusion network image-level classifier predicting the final CIN grade by merging vertical segment sequences. RESULTS: The model produces the CIN classification results and also determines the vertical segment contributions to CIN grade prediction. CONCLUSION: Experiments show that DeepCIN achieves pathologist-level CIN classification accuracy.

6.
Case Rep Neurol Med ; 2019: 1748739, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31312534

RESUMEN

Malignant gliomas account for 60% of all primary brain tumors in adults. Glioblastoma Multiforme (GBM) is the most common primary glial tumor with a dismal prognosis and a median survival of approximately 14 months. Extra-neural metastases from primary brain tumors are unusual with an incidence rate of less than 2%. This has been attributed to factors such as short survival, lack of true lymphatics in the CNS, and physical barriers provided by the dura, extracellular matrix, and basement membrane. Although most GBMs occur sporadically, there is a known association with therapeutic radiation exposure and with work in nuclear disaster cleanup. To our knowledge, no case of GBM with metastasis occurring in a patient with occupational radiation exposure currently exists in the literature. In this article, we present a case of GBM with lung metastasis occurring in a 51-year-old Caucasian male, whose history is significant for occupational exposure to ionizing radiation, and review the literature on GBM risk factors and potential mechanisms of metastasis.

7.
Cytojournal ; 14: 17, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28828030

RESUMEN

BACKGROUND: The Paris System for Reporting Urinary Cytology represents a significant improvement in classification of urinary specimens. The system acknowledges the difficulty in cytologically diagnosing low-grade urothelial carcinomas and has developed categories to deal with this issue. The system uses six categories: unsatisfactory, negative for high-grade urothelial carcinoma (NHGUC), atypical urothelial cells, suspicious for high-grade urothelial carcinoma, high-grade urothelial carcinoma, other malignancies and a seventh subcategory (low-grade urothelial neoplasm). METHODS: Three hundred and fifty-seven urine specimens were independently reviewed by four cytopathologists unaware of the previous diagnoses. Each cytopathologist rendered a diagnosis according to the Paris System categories. Agreement was assessed using absolute agreement and weighted chance-corrected agreement (kappa). Disagreements were classified as low impact and high impact based on the potential impact of a misclassification on clinical management. RESULTS: The average absolute agreement was 65% with an average expected agreement of 44%. The average chance-corrected agreement (kappa) was 0.32. Nine hundred and ninety-nine of 1902 comparisons between rater pairs were in agreement, but 12% of comparisons differed by two or more categories for the category NHGUC. Approximately 15% of the disagreements were classified as high clinical impact. CONCLUSIONS: Our findings indicated that the scheme recommended by the Paris System shows adequate precision for the category NHGUC, but the other categories demonstrated unacceptable interobserver variability. This low level of diagnostic precision may negatively impact the applicability of the Paris System for widespread clinical application.

8.
Am J Clin Pathol ; 147(5): 473-476, 2017 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-28371845

RESUMEN

OBJECTIVES: To determine the impact of consensus conferences on the frequency of discrepant cases in a surgical pathology practice. METHODS: The percentage of discrepancies in cases reviewed at a weekly consensus conference was calculated for the first and last months of a 13-month period. Both interrater agreement and agreement with the consensus diagnoses were assessed. A total of 309 diagnoses were performed for the first month and 518 for the last month. Both absolute and chance-corrected agreement were calculated for each period. RESULTS: Absolute agreement rate increased from 91.2% in the first month to 98.2% in the final month. Chance-corrected agreement increased from 0.80 in the first month to 0.97 in the final month. CONCLUSIONS: The consensus conference technique appears to be a useful method to reduce intradepartmental diagnostic discrepancies. Both absolute and chance-corrected agreement are improved by using consensus conferences.


Asunto(s)
Conferencias de Consenso como Asunto , Patología Quirúrgica/normas , Neoplasias del Cuello Uterino/diagnóstico , Biopsia , Femenino , Humanos
9.
Diagn Cytopathol ; 45(2): 107-112, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28110502

RESUMEN

BACKGROUND: Evaluation of the nuclear to cytoplasmic ratio is commonly used for assessment of the presence of malignancy and for grading and typing of malignant neoplasms. Despite its widespread usage, little information exists regarding the accuracy and reproducibility of non-automated assessment. METHODS: Forty-seven cells obtained from Papanicolaou stained urine cytologies were assessed by quantitative image analysis for nuclear area and cell area. The nuclear/cytoplasmic ratio was calculated. Visual estimates of the N/C ratio were made by six pathologists. Statistical analysis was performed to determine accuracy, precision, and interrater reliability. RESULTS: True N/C ratios varied from 0.02 to 0.81. 27% of cases demonstrated a true N/C ratio between 0.5 and 0.7. Quantitative estimates of N/C ratios were less precise and less accurate at high N/C ratios. The coefficient of variation was 27%. The majority of raters demonstrated decreased accuracy and precision of estimates as N/C ratio increased. Overall classification accuracy was 73%. Accuracy of classification was 53% for cases with a true N/C ratio between 0.4 and 0.8. Absolute interrater agreement was 75%. Chance corrected agreement (kappa) was 0.54. CONCLUSIONS: Visual quantitation of N/C ratio showed only a fair correlation with actual N/C ratio with correlation decreasing with increasing N/C ratio. In the critical range, 0.5-0.7 N/C ratio both interobserver correlation and correlation with true N/C ratio may be insufficiently accurate for precise category assignment as used in the Paris System. Diagn. Cytopathol. 2017;45:107-112. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Núcleo Celular/patología , Citoplasma/patología , Orina/citología , Neoplasias Urogenitales/patología , Urotelio/patología , Humanos , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados
10.
Pathol Res Pract ; 213(2): 126-129, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28040330

RESUMEN

OBJECTIVES: Traditionally, a 10% review has been the basis for quality assurance programs in anatomic pathology. The effectiveness of such reviews has been questioned and alternative methodologies suggested. The study investigates the error detection rates for four quality assurance protocols. METHODS: The detection rate for diagnostic errors in surgical pathology was calculated over a one year period using four different review procedures comprising: random 10% review, correlation of internal and external diagnoses following solicited external expert opinion, correlation of internal diagnoses with outside diagnoses in cases sent for review at a second institution treating the patient along with a focused review of dermatopathology cases over a 3 month period. Error rate was expressed as percentage of reviewed cases where the initial diagnosis differed from the review diagnosis. Error rates detected by each method were compared among the methods RESULTS: The 10% random review detected seventeen errors in 2147 cases (0.8%). Solicited case consultations requested by clinicians or internal pathologists detected five diagnostic errors in seventy cases (7.1%). Unsolicited reviews by outside institutions in the course of patient care detected three diagnostic errors in 190 cases (1.6%). Review of the dermatopathology material disclosed 5 diagnostic errors in 59 cases (8.5%). CONCLUSIONS: Focused reviews initiated by diagnostic concerns of a clinician or pathologist, unsolicited reviews because of treatment at another institution and sub-specialty based reviews appear to be more effective in detecting diagnostic errors than the 10% random review. Quality assurance programs should include focused reviews in addition to 10% random review to maximize error detection.


Asunto(s)
Errores Diagnósticos , Patología Quirúrgica/normas , Garantía de la Calidad de Atención de Salud , Humanos
11.
Blood Coagul Fibrinolysis ; 28(4): 342-347, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27676646

RESUMEN

: Acquired coagulopathies are common; uncommonly, adsorption of coagulation factors from the circulation into the tissues by pathologic amyloid exceeds the body's ability to produce factor and results in acquired factor deficiency. When amyloidosis does cause a coagulopathy, it is most often acquired factor X deficiency, but there are rare reports of amyloidosis being associated with other acquired factor deficiencies. We investigated a case of a severe bleeding diathesis, the cause of which was combined acquired factor V deficiency and concomitant acquired von Willebrand syndrome. Studies revealed prolonged prothrombin time and activated partial thromboplastin time. Mixing patient plasma with normal plasma corrected both the prothrombin time and activated partial thromboplastin time. Assays showed decreased factor V activity of 27%; Ristocetin cofactor activity was decreased at 49%, but von Willebrand antigen was elevated at 213%. Multimer analysis was consistent with type 2 von Willebrand syndrome. Lymph node biopsy documented amyloid light chain type (AL) amyloidosis; extraction of protein from the lymph node documented AL lambda light chain amyloid. Marrow biopsy documented IgG lambda myeloma. Immunohistochemical staining of the lymph node, using investigational polyvalent antibodies, demonstrated that both von Willebrand factor and factor V were identifiable in areas of amyloid deposition, providing evidence that these coagulation factors were adsorbed to the amyloid protein, resulting in accelerated clearance from the circulation, previously reported to be the mechanism of cases of acquired factor X deficiency in the setting of amyloidosis. Although there are case reports of acquired von Willebrand syndrome because of amyloidosis and case reports of acquired factor V deficiency because of amyloidosis, this appears to be the first reported case of concomitant acquired von Willebrand syndrome and acquired factor V deficiency because of amyloidosis, and the first report of localization of both von Willebrand protein and factor V protein to AL amyloid as a cause of a severe bleeding diathesis.


Asunto(s)
Amiloide/metabolismo , Trastornos Hemorrágicos/etiología , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/complicaciones , Factor V/metabolismo , Humanos , Cadenas Ligeras de Inmunoglobulina , Masculino , Persona de Mediana Edad , Factor de von Willebrand/metabolismo
12.
Pathol Res Pract ; 212(3): 190-5, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26839158

RESUMEN

BACKGROUND: IHC results for HER2/neu vary with replicate testing using the same antibody clone and when alternate clones are utilized. A number of factors appear to be responsible for this variability, including fixation times, equipment utilized and training and experience of staff. A number of studies have documented interobserver variability for a single antibody clone but few have evaluated reproducibility between antibody clones and which clones demonstrate the highest degree of interobserver reproducibility. DESIGN: We studied a series of 93 cases stained by both the HercepTest™ and the 4B5 clone for interobserver reproducibility. Formalin-fixed, paraffin-embedded sections were stained by the immunohistochemical technique using the manufactures directions for both the HercepTest™ and the 4B5 clone. FISH testing was performed on formalin-fixed paraffin embedded sections according to the PathVysion HER-2 DNA probe kit instructions. RESULTS: Absolute agreement rate for Hercep was 85%. Absolute agreement for 4B5 was 69%. This difference was statistically significant (p<0.0001). The chance-corrected agreement (weighted kappa) for the HercepTest™ was 79% and 71% for 4B5 (p<0.0001). Absolute agreement between antibody clones was 58% with the chance corrected agreement being 51%. Absolute agreement of 4B5 with FISH was significantly greater than that of the HercepTest™ (54% vs 35%). CONCLUSION: Agreement between evaluators was greater with the HercepTest. However, agreement with FISH results was superior for the 4B5 clone. Interobserver agreement was less than the 95% agreement threshold recommended by the ASCO/CAP guidelines for development of a new testing method for HER2 evaluation.


Asunto(s)
Anticuerpos Monoclonales , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/diagnóstico , Inmunohistoquímica/normas , Receptor ErbB-2/análisis , Femenino , Humanos , Hibridación Fluorescente in Situ/métodos , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados
13.
Breast J ; 21(4): 370-6, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25929243

RESUMEN

Mammographic studies have documented a number of architectural changes occurring around breast biopsy sites. These changes are well described in the radiological literature, but similar studies do not appear to be present in the pathology literature. We reviewed 100 consecutive mastectomy specimens from women who had undergone prior core needle or excisional biopsies. Multiple sections of the needle tract or excisional biopsy site were reviewed and morphologic findings reported. Hemorrhage, fat necrosis, granulation tissue, necrosis of fibrous tissue, and epithelium along with fibrosis and foreign body type giant cells were common features. Less frequent were areas of synovial metaplasia, atypical spindle cells, atypical duct-like structures, single atypical cells, squamous metaplasia, proliferations of abnormal blood vessels, and hemosiderin deposition. The misinterpretation of atypical spindle cells, single atypical cells, atypical duct-like structures and squamous metaplasia could result in the false-positive diagnosis of residual malignancy. Careful attention to the reactive nature of these changes aids in their distinction from carcinoma.


Asunto(s)
Biopsia con Aguja/métodos , Enfermedades de la Mama/diagnóstico , Enfermedades de la Mama/patología , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Diagnóstico Diferencial , Femenino , Enfermedad Fibroquística de la Mama/diagnóstico , Enfermedad Fibroquística de la Mama/patología , Humanos , Hiperplasia/diagnóstico , Hiperplasia/patología , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/patología , Valor Predictivo de las Pruebas , Pronóstico , Técnicas Estereotáxicas/instrumentación
15.
Thorac Cancer ; 5(1): 57-62, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26766973

RESUMEN

BACKGROUND: The purpose of this study is to determine prognostic factors and survival in patients who present with combined small-cell lung cancer (SCLC). METHODS: A retrospective review of combined SCLC histology in patients treated between1995-2010 was undertaken. Demographics, diagnostic information, disease characteristics, treatment modality, and survival were captured. Survival estimates were performed using Kaplan Meier analysis. Statistical significance was defined as P < 0.05. RESULTS: Forty-one patients were identified, and 35 records were available for analysis. Median age at diagnosis was 68 (range 50-85). The study included 20 (57%) women and 15 (43%) men; and 94% had a current or former history of smoking. Histology was SCLC/large cell carcinoma not otherwise specified in 28 (80%), and SCLC/adenocarcinoma or SCLC/squamous cell carcinoma in seven (20%). Cardiac or pulmonary comorbidities were present in 80% of patients, and 24 patients had metastatic disease at presentation. Twenty-eight patients received treatment of chemotherapy (n = 24), cranial radiotherapy (n = 5), or thoracic radiotherapy (n = 7). Staging was as follows: stage I-III (n = 11), stage IV (n = 24). Median survival was 15.4 months (range <1-53 months) and 3.4 months (range <1-21.9 months) for American Joint Committee on Cancer (AJCC) stage I-III and stage IV, respectively. Estimated overall six and 12 month survival was 82%, 55%, 37%, and 17% for stage I-III and stage IV, respectively. An improved overall survival rate was found for patients with an Eastern Cooperative Oncology Group performance status of <2, and no weight loss (P < 0.05). CONCLUSION: Akin to SCLC, advanced stage combined SCLC portends a poor prognosis. Perhaps novel chemotherapeutic drugs or targeted agents may improve outcomes for future patient populations.

16.
Reprod Sci ; 20(5): 514-23, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23427178

RESUMEN

Endometriosis-associated infertility manifests itself via multiple, poorly understood mechanisms. Our goal was to characterize signaling pathways, between peritoneal endometriotic lesions and the ovary, leading to failed ovulation. Genome-wide microarray analysis comparing ovarian tissue from an in vivo endometriosis model in the rat (Endo) with controls (Sham) identified 22 differentially expressed genes, including transiently expressed early growth response factor 1 (Egr1). The Egr1 regulates gene requisites for ovulation. The Egr1 promoter is responsive to tumor necrosis factor-alpha (TNF-α) signaling. We hypothesized that altered expression of ovarian EGR1 is induced by elevated peritoneal fluid TNF-α which is upregulated by the presence of peritoneal endometriosis. Endo rats, compared to controls, had more peritoneal fluid TNF-α and quantitative, spatial differences in Egr1 mRNA and EGR1 protein localization in follicular compartments. Interactions between elevated peritoneal fluid TNF-α and overexpression of follicular Egr1/EGR1 expression may affect downstream protease pathways impeding ovulation in endometriosis. Preliminary studies identified similar patterns of EGR1 protein localization in human ovaries from women with endometriosis and compared to those without endometriosis.


Asunto(s)
Líquido Ascítico/metabolismo , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Endometriosis/enzimología , Ovario/enzimología , Ovulación , Péptido Hidrolasas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Líquido Ascítico/inmunología , Sitios de Unión , Estudios de Casos y Controles , Modelos Animales de Enfermedad , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Endometriosis/genética , Endometriosis/inmunología , Endometriosis/fisiopatología , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Ovario/inmunología , Ovario/fisiopatología , Regiones Promotoras Genéticas , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal , Regulación hacia Arriba
17.
Case Rep Endocrinol ; 2011: 246872, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22937279

RESUMEN

Metastasis of uterine cancer to the head and neck is extremely rare. We report what we believe to be the first documented case of endometrioid adenocarcinoma metastasizing to the thyroid gland. An 80-year-old woman was referred to the otolaryngology service with a rapidly growing neck mass. The mass appeared to originate from the thyroid gland. Her clinical presentation was consistent with anaplastic thyroid carcinoma. A tracheostomy was performed. An open biopsy established the diagnosis of moderately differentiated adenocarcinoma, consistent with a gynecologic primary. The patient had undergone a hysterectomy 5 years prior for endometrioid adenocarcinoma. The thyroid tumor histology and immunophenotype corresponded well with her prior endometrial carcinoma, indicating that the thyroid mass was a metastasis from the endometrial primary. Radiotherapy appears to offer good local disease control in this rare case of endometrioid adenocarcinoma metastatic to the thyroid.

18.
Mol Cancer Res ; 8(2): 145-58, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20145038

RESUMEN

Oral squamous cell carcinoma (OSCC) has 50% 5-year survival rate, highlighting our limited understanding of the molecular events that contribute to disease progression. Microarray analyses of primary oral tumors have identified urinary-type plasminogen activator (uPA) and its receptor (uPAR) as key genes associated with human OSCC progression. The uPAR functions as both a proteinase receptor and an integrin ligand, modifying proteolysis, migration, integrin signaling, and cellular transcription. In the current study, uPAR expression levels were modified in OSCC cells followed by analysis of tumor growth in an in vivo orthotopic xenograft model and by transcriptional profiling. Overexpression of uPAR resulted in more infiltrative and less differentiated tumors, with ill-defined borders, cytologic atypia, and enhanced vascularity. Analysis of serial sections of both murine experimental tumors and microarrayed human OSCC showed a statistically significant association between uPAR and alpha(3) integrin colocalization in areas exhibiting extracellular signal-regulated kinase phosphorylation, suggesting that uPAR/alpha(3) integrin interaction potentiates extracellular signal-regulated kinase signaling in vivo. This is supported by cDNA microarray analysis, which showed differential expression of 148 genes (113 upregulated and 35 downregulated). Validation of gene expression changes in human OSCC using immunohistochemistry and quantitative real-time PCR showed increased growth factors, proteinases/inhibitors, and matrix components in uPAR-overexpressing tumors. Together, these results support a model wherein increased uPAR expression promotes alpha(3)beta(1) integrin association, resulting in increased mitogen-activated protein kinase signaling and transcriptional activation, leading to the formation of more aggressive tongue tumors. This combined approach has efficacy to identify additional biomarkers and/or prognostic indicators associated with aggressive human OSCC.


Asunto(s)
Carcinoma de Células Escamosas/genética , Regulación Neoplásica de la Expresión Génica/genética , Integrina alfa3beta1/genética , Neoplasias de la Boca/genética , Receptores del Activador de Plasminógeno Tipo Uroquinasa/genética , Transducción de Señal/genética , Animales , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/fisiopatología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Proteínas de la Matriz Extracelular/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Perfilación de la Expresión Génica/métodos , Humanos , Integrina alfa3beta1/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/genética , Ratones , Ratones Desnudos , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/fisiopatología , Invasividad Neoplásica/genética , Trasplante de Neoplasias/métodos , Análisis de Secuencia por Matrices de Oligonucleótidos , Péptido Hidrolasas/genética , Receptores del Activador de Plasminógeno Tipo Uroquinasa/metabolismo , Trasplante Heterólogo
19.
Histol Histopathol ; 24(2): 197-207, 2009 02.
Artículo en Inglés | MEDLINE | ID: mdl-19085836

RESUMEN

Oral squamous cell carcinoma (OSCC) represents 3% of all cancer deaths in the U.S. and is ranked one of the top 10 cancers worldwide. The 5-year survival rate has remained at a low 50% for the past several decades, necessitating discovery of novel biomarkers of aggressive disease and therapeutic targets. As overexpression of urinary type plasminogen activator and receptor (uPA/R) in OSCC is associated with malignant progression and poor outcome, cell lines were generated with either overexpression (SCC25-uPAR+) or silencing (SCC25-uPAR-KD) of uPAR. As SCC25-uPAR+ tumors behaved more aggressively both in vitro and in vivo, comparative cDNA microarray analysis was used to identify additional genes that may be associated with aggressive tumors. Four members of the human tissue kallikrein family (KLK 5, 7, 8, and 10) were identified and real-time RT-PCR (qPCR) was used to verify and quantify gene expression. qPCR analysis revealed 2.8-, 5.3-, 4.0-, and 3.5-fold increases in gene expression for KLK5, 7, 8, and 10, respectively, in SCC25-uPAR+ versus SCC25-uPAR-KD. Immunohistochemical analysis demonstrated strong reactivity for KLKs 5, 7, 8 and 10 in both orthotopic murine tumors and human OSCC tissues. Control experiments show lack of reactivity against KLK3 (prostate specific antigen). These results demonstrate that kallikreins 5, 7, 8, and 10 are abundantly expressed in human OSCC and may be implicated in malignant progression.


Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Regulación Neoplásica de la Expresión Génica , Calicreínas/biosíntesis , Neoplasias de la Boca/metabolismo , Animales , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Humanos , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
20.
Surgery ; 144(5): 786-92, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19081022

RESUMEN

BACKGROUND: Anastomotic leaks after colorectal operation continue to be a significant cause of morbidity. A covered endoluminal stent could seal a leak and eliminate the need for diversion. The aim of this study was to test the efficacy of a temporary covered stent to prevent leak related complications. METHODS: Sixteen adult pigs (80-120 lbs) underwent open transection of the rectosigmoid followed by anastomosis with a circular stapler. Eight animals (study group) underwent endoscopic placement of a 21-mm covered polyester stent. Eight control group animals were left without stents. In all animals, a 2-cm leak was created along the anterior portion of the anastomosis. The animals were killed after 2 weeks and evaluated for abdominal infection, fistulae, and adhesions. The anastomosis was excised and the following parameters were assessed by a pathologist blinded to treatment: mucosal interruption (mm), inflammatory response, collagen type I and III, granulation, and fibrosis (grade 0-4). RESULTS: Stents were spontaneously expelled between postoperative days 6 and 9. At necropsy, none of the animals in the study group had leak related complications, whereas in the control group, 5 (63%) developed intraabdominal infection (4 abscesses, 1 fistula) at the anastomosis (P = .002). Dense adhesions to the anastomosis were found in 7 (88%) control animals. On histology, anastomotic sites in the study group had significantly less mucosal interruption and granulation. Two pigs in the study group died on postoperative day 7, one due to evisceration and one from bladder necrosis. The mortality result is not different from controls (P = .47), both events seem to be unrelated to stent placement. CONCLUSION: Temporary placement of a covered polyester stent across a colorectal anastomosis prevents leak-related complications and supports the healing of anastomotic leaks.


Asunto(s)
Colon Sigmoide/cirugía , Recto/cirugía , Stents , Grapado Quirúrgico/efectos adversos , Dehiscencia de la Herida Operatoria/prevención & control , Cicatrización de Heridas , Anastomosis Quirúrgica/efectos adversos , Animales , Materiales Biocompatibles Revestidos , Colon Sigmoide/patología , Modelos Animales de Enfermedad , Masculino , Poliésteres , Recto/patología , Siliconas , Dehiscencia de la Herida Operatoria/etiología , Dehiscencia de la Herida Operatoria/patología , Porcinos
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