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1.
Medicine (Baltimore) ; 99(8): e18889, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080073

RESUMO

RATIONALE: Prostate cancer along with colorectal and lung cancers accounts for 42% of cancer cases in men globally. It is the first cancer indication for which the use of active immunotherapy, Sipuleucel-T (Provenge) was granted by the FDA in 2010. This study presents a case of prostate carcinoma and the tumour remission observed after administration of a personalised Dendritic cell vaccine (APCEDEN). PATIENT CONCERNS: A 58 years old Caucasian male diagnosed with prostate carcinoma with GLEASON score 8. The patient had previously been diagnosed with Renal Cell Carcinoma (RCC) in 1996 and had undergone nephrectomy of the right kidney. PET CT scan revealed multiple intensely PSMA avid lesions noted in both lobes of the prostate gland with SUVmax -28.3 and the prostate gland measuring 3.2 × 3.2 cm displaying maximum dimensions. DIAGNOSIS: FNAC followed by PETCT confirmed CA Prostate and further supported by increased serum PSA level. INTERVENTIONS: The patient underwent personalised Dendritic Cell Immunotherapy APCEDEN regimen of six doses biweekly, in a time frame of 3 months were given both via intravenous and intradermal route. Six months post completion of APCEDEN, the patient was administered 6 booster shots for 6 months. OUTCOMES: Progressive remission of carcinoma was observed along with reduction in PSA and Testosterone levels. PET CT showed decline in PSMA avidity by 50% with SUVmax -14.0 and normal size and shape of prostate gland. LESSONS: Prostate carcinoma is the second most common cancer in men with majority of them exhibiting locally advanced disease. Apparently 20% to 30% of them are categorized as relapsed cases after various therapeutic interventions. Modulating immune system is an emerging therapy termed as Immunotherapy and potentiates the killing cancer cells via immune activation. Interestingly, prostate cancer is slow growing and it provides the scope and time to mount an anti-tumor response which makes it an attractive target for immunotherapy. This case study demonstrates the efficacy of APCEDEN Immunotherapy regimen resulting in a significant disease remission benefiting the patient.


Assuntos
Imunoterapia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Carcinoma , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Lectinas Tipo C/imunologia , Masculino , Glicoproteínas de Membrana/imunologia , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Nefrectomia/métodos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico por imagem , Receptores Imunológicos/imunologia , Indução de Remissão , Resultado do Tratamento
2.
Urology ; 137: 126-132, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899229

RESUMO

OBJECTIVE: To assess the impact of concomitant targeted biopsies (TB) for predicting final disease reclassification in MRI-positive low-risk prostate cancer patients eligible for active surveillance (AS) on systematic biopsies (SB). MATERIALS AND METHODS: From a prospective database, we included all prebiopsy MRI-positive men fulfilling AS criteria at diagnosis (Toronto [n = 114], UCSF [n = 82], or PRIAS [n = 60] criteria) on SB. All patients underwent a combination of SB and software-based fusion TB, and an immediate radical prostatectomy. The primary endpoints were the pathologic upgrading and upstaging rates. RESULTS: Biopsy grade group was upgraded to grade group (GG) 2 and to GG≥3 on TB in 65.9%-76.7% and in 12.2-16.7%, respectively. The rate of GG ≥3 in radical prostatectomy specimens varied from 31.6% to 43.3% with no relation between strictest criteria and lower upgrading rates. The proportion of not organ-confined disease (35%-39%) was comparable among the AS cohorts. Negative TB was strongly associated with the absence of final GG ≥3. Tumor grade on TB was significantly correlated with the risk of final GG ≥3 in both Toronto and UCSF cohorts, not in the PRIAS cohort. In the PRIAS cohort, the only independent predictive factor for GG ≥3 disease was the maximal tumor length in any core (P = .034). CONCLUSION: In MRI-positive patients, the risk of disease reclassification was comparable whatever the SB-based AS criteria used. TB were predictive of final upgrading, with a varied impact according to the AS criteria. SB features remained relevant for reclassification prediction even in case of positive TB. The risk of upstaged disease remains important, approximately one third, and neither TB/SB parameters nor MRI findings could accurately predict it.


Assuntos
Biópsia Guiada por Imagem/métodos , Imagem por Ressonância Magnética Intervencionista/métodos , Gradação de Tumores , Próstata , Prostatectomia , Neoplasias da Próstata , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Gradação de Tumores/estatística & dados numéricos , Estadiamento de Neoplasias/métodos , Estadiamento de Neoplasias/estatística & dados numéricos , Valor Preditivo dos Testes , Próstata/diagnóstico por imagem , Próstata/patologia , Prostatectomia/métodos , Prostatectomia/estatística & dados numéricos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Medição de Risco
3.
J Appl Oral Sci ; 28: e20190198, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31800876

RESUMO

other: Pathological parameters have been indicated as tumor prognostic factors in oral carcinoma. OBJECTIVE: The objective of this study was to investigate the impact of pathological parameters on prognosis of patients affected only by tongue and/or floor of the mouth squamous cell carcinoma (SCC). METHODOLOGY: In total, 380 patients treated in the Brazilian National Cancer Institute (INCA) from 1999 to 2006 were included. These patients underwent radical resection followed by neck dissection. The clinical and pathological characteristics were recorded. The Kaplan-Meier method and Cox proportional hazards model were used in survival analysis. Overall survival (OS), cancer-specific survival (CSS) and disease-free interval (DFI) were estimated. Cox residuals were evaluated using the R software version 3.5.2. Worst OS, CSS and DFI were observed in patients with tumors in advanced pathological stages (p<0.001), with the presence of perineural invasion (p<0.001) and vascular invasion (p=0.005). RESULTS: Advanced pathological stage and the presence of a poorly differentiated tumor were independent prognostic factors for OS and CSS. However, advanced pathological stage and perineural invasion were independent predictors of a shorter OS, DFI and CSS. CONCLUSION: Pathological stage and perineural invasion were the most significant pathological variables in survival analysis in tongue and/or floor of the mouth SCC.


Assuntos
Carcinoma de Células Escamosas/patologia , Soalho Bucal/patologia , Neoplasias Bucais/patologia , Neoplasias da Língua/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Neoplasias Bucais/cirurgia , Esvaziamento Cervical/métodos , Gradação de Tumores/métodos , Estadiamento de Neoplasias , Análise de Regressão , Fatores de Tempo , Neoplasias da Língua/mortalidade , Neoplasias da Língua/cirurgia , Adulto Jovem
4.
Dis Colon Rectum ; 63(1): 53-59, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31633602

RESUMO

BACKGROUND: Total mesorectal excision is associated with decreased local recurrence and improved disease-free survival following rectal cancer resection. The extent to which total mesorectal excision has been adopted in the United States is unknown. OBJECTIVE: We sought to assess trends in total mesorectal excision performance and grading in Michigan hospitals. DESIGN: This is a retrospective cohort study from the Michigan Surgical Quality Collaborative. Trends in total mesorectal excision performance and grade assignment were analyzed by using χ tests and linear regression. SETTINGS: Participating hospitals (initially 14 hospitals, now 38) abstracted medical records data for rectal cancer cases from 2007 to 2016. PATIENTS: Patients who underwent rectal cancer resection were included. MAIN OUTCOME MEASURE: The main outcome measures were surgeon-documented total mesorectal excision performance and pathologist-reported total mesorectal excision grade. RESULTS: Of 510 rectal cancer cases, 367 (72.0%) had surgeon-reported total mesorectal excision performance and 78 (15.3%) had pathologist-reported total mesorectal excision grade. Between-hospital variability in total mesorectal excision performance ranged from 0% to 97% and total mesorectal excision grading ranged from 0% to 90%. Total mesorectal excision grading was associated with a higher likelihood of also having adequate lymph node assessment (88.5% versus 71.9%, p = 0.002). There has been a statistically significant trend toward an increase in total mesorectal excision grading in the original 14 hospitals (p = 0.001), but not in the complete cohort of all hospitals (p = 0.057). LIMITATIONS: This is a retrospective cohort design with sampled rectal cancer cases. In addition, there is insufficient granularity to capture all factors associated with total mesorectal excision performance or grade assignment. CONCLUSIONS: The rates of total mesorectal excision performance and grade assignment are widely variable throughout the state of Michigan. Overall, grade assignment remains very low. This suggests an opportunity for quality improvement projects to increase total mesorectal excision performance and grading, involving both the surgeons and pathologists for effective implementation. See Video Abstract at http://links.lww.com/DCR/B53. IMPLEMENTACIÓN DE LA ESCISIÓN MESORRECTAL TOTAL Y LA CLASIFICACIÓN POR ESCISIÓN MESORRECTAL TOTAL PARA EL CÁNCER RECTAL: UN ESTUDIO A NIVEL ESTATAL.: La escisión mesorrectal total se asocia con una menor recurrencia local y una mejor supervivencia libre de enfermedad después de la resección del cáncer rectal. Se desconoce hasta que punto se ha adoptado la escisión mesorrectal total en los Estados Unidos.Se intento evaluar las tendencias en el rendimiento y la clasificación de la escisión mesorrectal total en los hospitales de Michigan.Este es un estudio de cohorte retrospectivo de la "Michigan Surgical Quality Collaborative". Las tendencias en el rendimiento de la escisión mesorrectal total y la asignación de grado se analizaron mediante pruebas de chi-cuadrada y regresión lineal.Los hospitales participantes (inicialmente 14 hospitales, ahora 38) extrajeron datos de registros médicos de los casos de cáncer rectal desde 2007 hasta 2016.Pacientes que se sometieron a resección de cáncer rectal.Las principales medidas de resultado fueron el rendimiento de la escisión mesorrectal total documentado por el cirujano y el grado de escisión mesorrectal total informada por el patólogo.De 510 casos de cáncer rectal, 367 (72.0%) tenían un rendimiento de escisión mesorrectal total reportado por el cirujano y 78 (15.3%) tenían un grado de escisión mesorrectal total reportado por el patólogo. La variabilidad entre hospitales en el rendimiento de la escisión mesorrectal total varió del 0 al 97% y la clasificación de la escisión mesorrectal total varió del 0 al 90%. La clasificación de la escisión mesorrectal total se asoció con una mayor probabilidad de tener también una evaluación adecuada de los ganglios linfáticos (88.5% versus 71.9%, p = 0.002). Ha habido una tendencia estadísticamente significativa hacia un aumento en la clasificación de la escisión mesorrectal total en los 14 hospitales originales (p = 0.001), pero no en la cohorte completa de todos los hospitales (p = 0.057).Diseño de cohorte retrospectivo con casos de cáncer rectal muestreados. Además, no hay suficiente granularidad para capturar todos los factores asociados con el rendimiento de la escisión mesorrectal total o la asignación de grados.Las tasas de rendimiento de escisión mesorrectal total y asignación de grado son muy variables en todo el estado de Michigan. En general, la asignación de calificaciones sigue siendo muy baja. Esto sugiere una oportunidad para que los proyectos de mejora de la calidad aumenten el rendimiento y la clasificación de la escisión mesorrectal total, involucrando tanto a los cirujanos como a los patólogos para una implementación efectiva. Vea el resumen del video en http://links.lww.com/DCR/B53.


Assuntos
Gradação de Tumores/métodos , Protectomia/métodos , Melhoria de Qualidade , Neoplasias Retais/cirurgia , Reto/cirurgia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Michigan/epidemiologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Retais/diagnóstico , Reto/diagnóstico por imagem , Estudos Retrospectivos , Resultado do Tratamento
5.
Georgian Med News ; (294): 128-131, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31687964

RESUMO

Histone modifications represent one of the types of epigenetic changes. Histones, undergo different types of epigenetic modifications, including the phosphorylation of serine residues. pHH3 antibodies specifically detect histon-3 protein, when phosphorylated at 10th and 28th serine residues. Traditionally pHH3 antibodies are used as proliferation marker, as it detects cells in late G2 and M phase. We studied the distribution of phosphor-histon-3 in epithelial tumors of the ovary and its relationship with ER, PR, Ki67, p53 and BCL2. Altogether, we investigated postoperative material from 160 patients. Standard immunohistochemistry was used to detect, phosphohistone-H3 (pHH3), ER, PR, Ki67, p53 and BCL2. The results of our study showed that phosphohistone-H3 expression is negatively associated with the expression of ER and PR expression, as well as with BCL2 expression, on the other hand it positively correlates with Ki67 and mutant p53 (p<0.05). In addition, the expression of phosphohistone-H3 is detected in Ki67 negative cases and its expression is increased along with the increase of malignancy grade. Our study results indicate that PHH3 might be used as an additional marker for the assessment of proliferation and malignancy potential of epithelial tumors of the ovary.


Assuntos
Epigênese Genética , Histonas/análise , Antígeno Ki-67/análise , Índice Mitótico/métodos , Gradação de Tumores/métodos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Fosforilação , Biomarcadores Tumorais , Proliferação de Células , Feminino , Humanos , Imuno-Histoquímica/métodos
6.
Medicine (Baltimore) ; 98(42): e17627, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626145

RESUMO

Adjuvant radiation therapy (ART) is recommended without consideration of radical prostatectomy Gleason score (RP GS) for cases with adverse features. We compared the outcomes of pathologically localized high-grade (GS 8-10) prostate cancer (PC) with those of pT3 GS 7 PC.A total of 1585 men who underwent RP between 1995 and 2015 comprised the cohort, which was divided into group 1 (RP GS 7(3 + 4) and pT3; n = 760), group 2 (RP GS 7(4 + 3) and pT3; n = 565), and group 3 (RP GS 8-10 and pT2; n = 260). Biochemical recurrence (BCR), all-cause mortality (ACM), and PC-specific mortality (PCSM) risk were compared among groups using Cox regression and competing risk analysis.At a median follow-up of 58 months (interquartile range: 37-85), 721 men experienced BCR and 84 died (22 due to PC). BCR-free survival rates were lower in group 3 than in group 1 (P < .001); nevertheless, no difference was observed between groups 2 and 3 (P = .638). Furthermore, no difference in ACM was noted among groups. PCSM rates were higher in group 3 than in groups 1 and 2 (P = .001 and P = .005, respectively). This association persisted in multivariate models after adjustment for clinicopathological variables.Patients with RP GS 8-10 and pT2 PC had higher BCR and PCSM rates than those with RP GS 7 and pT3 PC. Localized high-grade PC should be considered in decision-making for ART.


Assuntos
Gradação de Tumores/métodos , Próstata/patologia , Prostatectomia/métodos , Neoplasias da Próstata/diagnóstico , Idoso , Causas de Morte/tendências , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Próstata/cirurgia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/cirurgia , República da Coreia/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida/tendências
7.
Am J Dermatopathol ; 41(10): 722-732, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31584883

RESUMO

Both architectural and cytologic characteristics are used to distinguish benign from malignant sebaceous neoplasms; however, specific cytopathologic features of sebocytes have not been well defined. The authors assessed architectural and cytological features of 63 sebaceous neoplasms [15 sebaceous hyperplasias, 12 sebaceomas, 16 sebaceous adenomas (SA), 14 sebaceous carcinomas (SC), and 6 ocular sebaceous carcinoma (OSC)] to investigate whether cytological grading may facilitate classification of lesions. Among other criteria, nuclear pleomorphism (size, nucleolar appearance, membrane irregularity, crowding, mitoses, and chromatin pattern) was assessed and 3 theoretical nuclear grades established. Immunohistochemistry for CK10, p16, adipophilin and ki67 was performed on 7 cases of each type of tumor. Most sebaceous neoplasms, except OSC, showed a bland architectural silhouette. However, SA, SC, and OSC revealed larger nuclei (≥14 µm in ≥50% of cases), evident to multiple nucleoli, membrane irregularity, coarse to clumped chromatin, and nuclear grade ≥2 (latter in ≥56% of cases); by contrast, sebaceous hyperplasia and sebaceomas showed smaller nuclei (≤10 µm in ≥50% of cases), smooth borders, inconspicuous nucleoli, fine chromatin, and grade 1 nuclei (latter in 100% of cases). In the setting of a well-circumscribed architecture, cytologic features gain importance in the classification of sebaceous neoplasms. Interestingly, cytologic similarities found in SA and SC may indicate a close relationship of both neoplasms.


Assuntos
Gradação de Tumores/métodos , Neoplasias das Glândulas Sebáceas/classificação , Neoplasias das Glândulas Sebáceas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Clin Hemorheol Microcirc ; 73(1): 105-111, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31561351

RESUMO

INTRODUCTION: Multiparametric-Magnetic Resonance Imaging (mpMRI)-Ultrasound fusion guided biopsy (Fbx) has emerged as the new standard of risk stratification for prostate cancer (PCa) with superior detection rates of clinically significant PCa than randomized biopsy. In the present study, we evaluated patients with suspicion of clinically significant PCa on mpMRI, but histopathologically proven Gleason 6 PCa in Fbx. MATERIAL AND METHODS: Between 2015 and 2019, 849 patients underwent Fbx and concurrent systematic 12-core biopsy at our department. 234 patients were diagnosed with Gleason 6 PCa in either mpMRI-targeted and/or concurrent systematic biopsy. Patients were analyzed regarding PSA, mpMRI findings according to PI-RADS classification, histopathological results of Fbx and systematic 12-core biopsy. 99/234 patients were also analyzed in regards of histopathology of the whole-mount specimen of subsequent radical prostatectomy (RP). RESULTS: In 131/234 patients (56%), Gleason 6 PCa was detected in the mpMRI target. In 103/234 patients (44%), Gleason 6 PCa was detected in the concurrent systematic 12-core biopsy with negative mpMRI-targeted biopsy. Men with evidence of Gleason 6 in the mpMRI target had significantly higher amounts of overall positive biopsies (median 4 vs. 2, p < 0.001) and higher maximum tumor infiltration per biopsy core (30% vs. 20%, p < 0.001) compared to men with negative mpMRI-targeted biopsy. Detection of Gleason 6 in mpMRI Target lesions correlated significantly with the PI-RADS score (p < 0.001). Patients with positive mpMRI-target had significantly higher tumor infiltration in whole-mount specimen after prostatectomy (20% vs. 15%, p = 0.0026) compared to men without detection of Gleason 6 in mpMRI-targeted biopsy but in additional systematic biopsy. CONCLUSION: Detection of Gleason 6 PCa in mpMRI-targeted biopsy indicates higher tumor burden compared to detection of Gleason 6 PCa in concurrent systematic biopsy and negative mpMRI-targeted biopsy.


Assuntos
Biópsia Guiada por Imagem/métodos , Gradação de Tumores/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia
9.
Int J Comput Assist Radiol Surg ; 14(11): 1981-1991, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31555998

RESUMO

PURPOSE: The World Health Organization (WHO) grading system of pancreatic neuroendocrine tumor (PNET) plays an important role in the clinical decision. The rarity of PNET often negatively affects the radiological application of deep learning algorithms due to the low availability of radiological images. We tried to investigate the feasibility of predicting WHO grades of PNET on contrast-enhanced magnetic resonance (MR) images by deep learning algorithms. MATERIALS AND METHODS: Ninety-six patients with PNET underwent preoperative contrast-enhanced MR imaging. Fivefold cross-validation was used in which five iterations of training and validation were performed. Within every iteration, on the training set augmented by synthetic images generated from generative adversarial network (GAN), a convolutional neural network (CNN) was trained and its performance was evaluated on the paired internal validation set. Finally, the trained CNNs from cross-validation and their averaged counterpart were separately assessed on another ten patients from a different external validation set. RESULTS: Averaging the results across the five iterations in the cross-validation, for the CNN model, the average accuracy was 85.13% ± 0.44% and micro-average AUC was 0.9117 ± 0.0053. Evaluated on the external validation set, the average accuracy of the five trained CNNs ranges between 79.08 and 82.35%, and the range of micro-average AUC was between 0.8825 and 0.8932. The average accuracy and micro-average AUC of the averaged CNN were 81.05% and 0.8847, respectively. CONCLUSION: Synthetic images generated from GAN could be used to alleviate the difficulty of radiological image collection for uncommon disease like PNET. With the help of GAN, the CNN showed the potential to predict the WHO grades of PNET on contrast-enhanced MR images.


Assuntos
Meios de Contraste/farmacologia , Aprendizado Profundo , Imagem por Ressonância Magnética/métodos , Gradação de Tumores/métodos , Tumores Neuroendócrinos/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Organização Mundial da Saúde
10.
World Neurosurg ; 132: e366-e390, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31476455

RESUMO

OBJECTIVE: Meningioma grading is relevant to therapy decisions in complete or partial resection, observation, and radiotherapy because higher grades are associated with tumor growth and recurrence. The differentiation of low and intermediate grades is particularly challenging. This study attempts to apply radiomics-based shape and texture analysis on routine multiparametric magnetic resonance imaging (MRI) from different scanners and institutions for grading. METHODS: We used MRI data (T1-weighted/T2-weighted, T1-weighted-contrast-enhanced [T1CE], fluid-attenuated inversion recovery [FLAIR], diffusion-weighted imaging [DWI], apparent diffusion coefficient [ADC]) of grade I (n = 46) and grade II (n = 25) nontreated meningiomas with histologic workup. Two experienced radiologists performed manual tumor segmentations on FLAIR, T1CE, and ADC images in consensus. The MRI data were preprocessed through T1CE and T1-subtraction, coregistration, resampling, and normalization. A PyRadiomics package was used to generate 990 shape/texture features. Stepwise dimension reduction and robust radiomics feature selection were performed. Biopsy results were used as standard of reference. RESULTS: Four statistically independent radiomics features were identified as showing the strongest predictive values for higher tumor grades: roundness-of-FLAIR-shape (area under curve [AUC], 0.80), cluster-shades-of-FLAIR/T1CE-gray-level (AUC, 0.80), DWI/ADC-gray-level-variability (AUC, 0.72), and FLAIR/T1CE-gray-level-energy (AUC, 0.76). In a multivariate logistic regression model, the combination of the features led to an AUC of 0.91 for the differentiation of grade I and grade II meningiomas. CONCLUSIONS: Our results indicate that radiomics-based feature analysis applied on routine MRI is viable for meningioma grading, and a multivariate logistic regression model yielded strong classification performances. More advanced tumor stages are identifiable through certain shape parameters of the lesion, textural patterns in morphologic MRI sequences, and DWI/ADC variability.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Gradação de Tumores/métodos , Neuroimagem/métodos , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Neoplasias Meníngeas/patologia , Meningioma/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Transplant Proc ; 51(6): 1861-1866, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399170

RESUMO

BACKGROUND: To evaluate the diagnostic accuracy of intravoxel incoherent motion (IVIM) parameters in estimation of hepatocellular carcinoma (HCC) grading. MATERIALS AND METHODS: Twenty-nine patients with histopathologically diagnosed as 42 HCC at explant were included in this retrospective study. All patients were examined by 1.5T magnetic resonance imaging with the use of 4-channel phased array body coil. In addition to routine pre- and postcontrast sequences, IVIM (16 different b factors varying from 0 to 1300 s/mm2) and conventional diffusion-weighted imaging (3 different b factors of 50, 400, 800 s/mm2) were obtained with single-shot echo planar spin echo sequence. Apparent diffusion coefficient (ADC) and IVIM parameters including mean D (true diffusion coefficient), D* (pseudo-diffusion coefficient associated with blood flow), and f (perfusion fraction) values were calculated. Histopathologically, HCC was classified as low (grade 1, 2) and high (grade 3, 4) grade in accordance with the Edmondson-Steiner score. Quantitatively, ADC, D, D*, and f values were compared between the low- and high-grade groups by Student t test. The relationship between the parameters and histologic grade was analyzed using the Spearman's correlation test. To evaluate the diagnostic performance of the parameters, receiver operating characteristic analysis was performed. RESULTS: High-grade HCCs had significantly lower ADC and D values than low grade groups (P = .005 and P = .026, retrospectively); ADC and D values were inversely correlated with tumor grade (r = -0.519, P = .011, r = -0.510, P = .026, respectively). High-grade HCCs had significantly higher f values when compared with the low-grade group (P = .005). The f values were positively correlated with tumor grade (r = 0.548, P = .007). The best discriminative parameter was f value. Cut-off value of 32% of f values showed sensitivity of 75.6% and a specificity of 73.5%. CONCLUSION: ADC values and IVIM parameters such as f values appear to reflect the grade of HCCs.


Assuntos
Carcinoma Hepatocelular/patologia , Imagem de Difusão por Ressonância Magnética/estatística & dados numéricos , Interpretação de Imagem Assistida por Computador/estatística & dados numéricos , Neoplasias Hepáticas/patologia , Gradação de Tumores/estatística & dados numéricos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento (Física) , Gradação de Tumores/métodos , Curva ROC , Valores de Referência , Estudos Retrospectivos , Sensibilidade e Especificidade , Estatísticas não Paramétricas
12.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 36(4): 581-589, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31441258

RESUMO

In order to solve the pathological grading of hepatocellular carcinomas (HCC) which depends on biopsy or surgical pathology invasively, a quantitative analysis method based on radiomics signature was proposed for pathological grading of HCC in non-contrast magnetic resonance imaging (MRI) images. The MRI images were integrated to predict clinical outcomes using 328 radiomics features, quantifying tumour image intensity, shape and text, which are extracted from lesion by manual segmentation. Least absolute shrinkage and selection operator (LASSO) were used to select the most-predictive radiomics features for the pathological grading. A radiomics signature, a clinical model, and a combined model were built. The association between the radiomics signature and HCC grading was explored. This quantitative analysis method was validated in 170 consecutive patients (training dataset: n = 125; validation dataset, n = 45), and cross-validation with receiver operating characteristic (ROC) analysis was performed and the area under the ROC curve (AUC) was employed as the prediction metric. Through the proposed method, AUC was 0.909 in training dataset and 0.800 in validation dataset, respectively. Overall, the prediction performances by radiomics features showed statistically significant correlations with pathological grading. The results showed that radiomics signature was developed to be a significant predictor for HCC pathological grading, which may serve as a noninvasive complementary tool for clinical doctors in determining the prognosis and therapeutic strategy for HCC.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Gradação de Tumores/métodos , Humanos , Imagem por Ressonância Magnética , Curva ROC
13.
World Neurosurg ; 130: e775-e785, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31295606

RESUMO

OBJECTIVE: Secreted phosphoprotein 1 (SPP1) is an important extracellular glycoprotein that is associated with immune regulation, tumorigenesis, and cell signaling. However, the prognostic value of SPP1 in patients with glioma has not yet been clarified, especially in lower-grade gliomas. The objective of this study is to evaluate the prognostic merit of SPP1 in lower-grade gliomas. METHODS: The messenger RNA (mRNA) expression of SPP1 in about 1000 cancer cell lines was explored by using the data from the Cancer Cell Line Encyclopedia database. The Oncomine database was mined to evaluate the mRNA expression of SPP1 in lower-grade glioma, glioblastoma, and normal brain tissues. The correlation between SPP1 mRNA expression and overall survival of patients with glioma from The Cancer Genome Atlas database was analyzed. RESULTS: SPP1 mRNA expression of glioma was ranked as the eighth highest of all cancer cell lines in the Cancer Cell Line Encyclopedia database. The data from the Oncomine database suggested that SPP1 expression was significantly high in glioblastoma compared with normal brain tissues but was not significantly high in lower-grade glioma compared with normal brain tissue. Analysis of the RNA-Seq data from The Cancer Genome Atlas database showed that the increased SPP1 mRNA expression in lower-grade glioma was significantly associated with poor survival outcomes in patients with lower-grade glioma. Multivariate Cox regression analysis showed that SPP1 might be considered as an independent prognostic factor in lower-grade gliomas. CONCLUSIONS: The present study showed that SPP1 overexpression is related to worse overall survival in patients with lower-grade glioma. Moreover, SPP1 could be considered as an independent factor in lower-grade gliomas.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/metabolismo , Glioma/diagnóstico por imagem , Glioma/metabolismo , Osteopontina/metabolismo , Adulto , Idoso , Neoplasias Encefálicas/cirurgia , Feminino , Glioma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Prognóstico
14.
Pathology ; 51(5): 463-473, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31279442

RESUMO

The Gleason Grading system has been used for over 50 years to prognosticate and guide the treatment for patients with prostate cancer. At consensus conferences in 2005 and 2014 under the guidance of the International Society of Urological Pathology (ISUP), the system has undergone major modifications to reflect modern diagnostic and therapeutic practices. The 2014 consensus conference yielded recommendations regarding cribriform, mucinous, glomeruloid and intraductal patterns, the most significant of which was the removal of any cribriform pattern from Gleason grade 3. Furthermore, a Gleason score grouping system was endorsed which consisted of five grades where Gleason score 6 (3+3) was classified as grade 1 which better reflected the mostly indolent behaviour of these tumours. Another issue discussed at the meeting and subsequently endorsed was that in Gleason score 7 cases, the percentage pattern 4 should be recorded. This is especially important in situations where modern active surveillance protocols expand to include men with low volume pattern 4. While major progress was made at the conference, several issues were either not resolved or not discussed at all. Most of these items relate to details of assignment of Gleason score and ISUP grade in specific specimen types and grading scenarios. This detailed review looks at the 2014 ISUP conference results and subsequent literature from an international perspective and proposes several recommendations. The specific issues addressed are percentage pattern 4 in Gleason score 7 tumours, percentage patterns 4 and 5 or 4/5 in Gleason score 8-10 disease, minor (≤5%) high grade patterns when either 2 or 3 patterns are present, level of reporting (core, specimen, case), dealing with grade diversity among site (highest and composite scores) and reporting scores in radical prostatectomy specimens with multifocal disease. It is recognised that for many of these issues, a strong evidence base does not exist, and further research studies are required. The proposed recommendations mostly reflect consolidated expert opinion and they are classified as established if there was prior agreement by consensus and provisional if there was no previous agreement or if the item was not discussed at prior consensus conferences. For some items there are reporting options that reflect the local requirements and diverse practice models of the international urological pathology community. The proposed recommendations provide a framework for discussion at future consensus meetings.


Assuntos
Adenocarcinoma/patologia , Gradação de Tumores , Patologia , Neoplasias da Próstata/patologia , Urologia , Adenocarcinoma/classificação , Humanos , Masculino , Gradação de Tumores/métodos , Gradação de Tumores/normas , Patologia/métodos , Patologia/normas , Neoplasias da Próstata/classificação , Urologia/métodos , Urologia/normas
15.
World Neurosurg ; 130: e1015-e1019, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31306847

RESUMO

BACKGROUND: Most meningiomas are classified as World Health Organization (WHO) grade I. Adjuvant radiation therapy (RT) is commonly recommended for subtotal resections with documented progressive regrowth of lesions with venous sinus involvement. We investigated if recurrence of WHO grade I meningiomas was influenced by adjuvant RT. METHODS: From 2000 to 2014, patients with grade I meningiomas with at least one venous sinus involvement and at least 4 years of follow-up were included. Demographics, venous sinus involvement, histology, and extent of resection (EOR) were characterized. Because patients undergoing RT tend to differ from those for whom adjuvant therapy was not prescribed, we used propensity scores to adjust for confounding variables. RESULTS: Sixty-two patients were included; of these, 18 (29.0%) had recurrences. The mean age was 52.8 ± 12.3 years, and 79.0% were women. A total of 34 cases (54.8%) were submitted to adjuvant RT. Adjuvant RT was more frequent in those who had tumor recurrence (77.8% vs. 45.5%, P = 0.020). RT was more frequent in superior sagittal sinus (SSS) invasion (76.5% vs. 50.0%, P = 0.030) and less prevalent after gross total resection (GTR) (32.4% vs. 67.9%, P = 0.005). Propensity score adjusted analysis suggested no adjuvant RT benefit (odds ratio [OR], 2.51; 95% confidence interval [CI], 0.68-9.28; P = 0.167), independent of the EOR. SSS involvement increased recurrence risk (OR, 12.69; 95% CI, 1.46-110.27; P = 0.021), whereas GTR tended to decrease it (OR, 0.26; 95% CI, 0.06-1.09; P = 0.065). CONCLUSIONS: Adjuvant RT does not seem to be a pivotal criterion to reduce the recurrence rate in patients with grade I meningioma, even when venous sinuses are involved.


Assuntos
Cavidades Cranianas , Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Recidiva Local de Neoplasia/prevenção & controle , Pontuação de Propensão , Radioterapia Adjuvante/tendências , Adulto , Idoso , Cavidades Cranianas/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Radioterapia Adjuvante/métodos , Organização Mundial da Saúde
16.
Int J Radiat Oncol Biol Phys ; 105(4): 784-791, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31344432

RESUMO

PURPOSE: A noninvasive diagnostic method to predict the degree of malignancy accurately would be of great help in glioma management. This study aimed to create a highly accurate machine learning model to perform glioma grading. METHODS AND MATERIALS: Preoperative magnetic resonance imaging acquired for cases of glioma operated on at our institution from October 2014 through January 2018 were obtained retrospectively. Six types of magnetic resonance imaging sequences (T2-weighted image, diffusion-weighted image, apparent diffusion coefficient [ADC], fractional anisotropy, and mean kurtosis [MK]) were chosen for analysis; 476 features were extracted semiautomatically for each sequence (2856 features in total). Recursive feature elimination was used to select significant features for a machine learning model that distinguishes glioblastoma from lower-grade glioma (grades 2 and 3). RESULTS: Fifty-five data sets from 54 cases were obtained (14 grade 2 gliomas, 12 grade 3 gliomas, and 29 glioblastomas), of which 44 and 11 data sets were used for machine learning and independent testing, respectively. We detected 504 features with significant differences (false discovery rate <0.05) between glioblastoma and lower-grade glioma. The most accurate machine learning model was created using 6 features extracted from the ADC and MK images. In the logistic regression, the area under the curve was 0.90 ± 0.05, and the accuracy of the test data set was 0.91 (10 out of 11); using a support vector machine, they were 0.93 ± 0.03 and 0.91 (10 out of 11), respectively (kernel, radial basis function; c = 1.0). CONCLUSIONS: Our machine learning model accurately predicted glioma tumor grade. The ADC and MK sequences produced particularly useful features.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Glioma/diagnóstico por imagem , Aprendizado de Máquina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anisotropia , Astrocitoma/diagnóstico por imagem , Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Conjuntos de Dados como Assunto , Diagnóstico Diferencial , Imagem de Tensor de Difusão/métodos , Feminino , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Oligodendroglioma/diagnóstico por imagem , Oligodendroglioma/patologia , Estudos Retrospectivos , Adulto Jovem
17.
World Neurosurg ; 130: e324-e332, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31228703

RESUMO

BACKGROUND: Klotho, a single-pass transmembrane protein associated with premature aging, acts as a tumor suppressor gene by inhibiting insulin/insulin-like growth factor-1 and fibroblast growth factor pathways. Downregulated Klotho expression is reported in melanoma, mesothelioma, bladder, breast, gastric, cervix, lung, and kidney cancers and is associated with a poor prognosis. Klotho expression and Klotho promoter hypermethylation are predictive factors for patient prognosis. METHODS: To investigate the potential role of Klotho in glioblastoma-multiforme (GBM), 22 GBM samples were collected from the Sheba Tumor Bank and examined. RESULTS: We found that increased Klotho messenger ribonucleic acid (RNA) expression predicted longer survival (P = 0.03) of GBM patients. Methylation analysis was performed on bisulfite-treated deoxyribonucleic acid from the GBM patient samples using ionization time-of-flight mass spectrometry according to the Sequenom EpiTYPER protocols. Klotho promoter hypermethylation was detected in 65% of the GBM samples and correlated significantly with improved survival (P < 0.04). We found 3 major Klotho promotor hypermethylation sites located 585-579 bp, 540-533 bp, and 537-534 bp upstream of the transcription start site. Methylated deoxyribonucleic acid immunoprecipitation studies confirmed these results. Notably, the messenger RNA expression in these GBM samples revealed an unexpected linear correlation with methylation of these 3 hypermethylation sites identified in the Klotho promotor. Thus Klotho expression and methylation could predict prognosis in patients with GBM. CONCLUSIONS: Epigenetic regulation in GBM appears to be complicated. Specific CpG islands affect genes or micro RNAs that interact to control Klotho expression. The diverse effects of these islands may be due to unique factors of GBM.


Assuntos
Neoplasias Encefálicas/genética , Carcinogênese/genética , Progressão da Doença , Glioblastoma/genética , Glucuronidase/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/metabolismo , Carcinogênese/metabolismo , Carcinogênese/patologia , Regulação Neoplásica da Expressão Gênica , Glioblastoma/diagnóstico , Glioblastoma/metabolismo , Glioma/diagnóstico , Glioma/genética , Glioma/metabolismo , Glucuronidase/biossíntese , Humanos , Células MCF-7 , Gradação de Tumores/métodos , Prognóstico
18.
Virchows Arch ; 475(4): 445-455, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31240474

RESUMO

Bladder cancer tumors can be divided into two molecular subtypes referred to as luminal or basal. Each subtype may react differently to current chemotherapy or immunotherapy. Likewise, the technology required for comprehensive molecular analysis is expensive and not yet applicable for routine clinical diagnostics. Therefore, it has been suggested that the immunohistochemical expressions of only two markers, luminal (CK20+, CK5/6-) and basal (CK5/6+, CK20-), is sufficient to identify the molecular subtypes of bladder cancer. This would represent a molecular grade that could be used in daily practice. Molecular classification is done using immunohistochemistry to assess luminal-basal phenotype based on tissular expression of CK20 and CK5/6 as surrogate for luminal or basal subtypes, respectively. A series of 147 non-muscle-invasive bladder carcinoma cases was selected, and the tumors were divided into four subgroups based on the presence of CK20 and/or CK5/6, that is, null (CK20-, CK5/6-), mixed (CK20+, CK5/6+), basal (CK20-, CK5/6+), and luminal (CK20+, CK5/6-) categories. Survival analysis was estimated using the Kaplan-Meier method and the log-rank test. Hazard ratios were calculated by Cox multivariate analysis. The molecular grade included cases with null (n = 89), mixed (n = 6), basal (n = 20), and luminal (n = 32) phenotypes with differences in recurrence-free, progression-free and cancer-specific survival associated with molecular-grade categories in patients with low- or high-grade Ta, or high-grade T1 tumors. The multivariate analysis identified the luminal phenotype as a predictor of more aggressive neoplasms. Our findings provide a rationale to investigate luminal and basal subtypes of bladder cancer using two gene expression signatures as surrogate markers and show that non-muscle-invasive bladder carcinoma can be stratified into biologically and clinically different subgroups by using an immunohistochemical classifier.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/classificação , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/classificação , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/mortalidade , Feminino , Humanos , Queratina-20/análise , Queratina-20/biossíntese , Queratina-5/análise , Queratina-5/biossíntese , Queratina-6/análise , Queratina-6/biossíntese , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Fenótipo , Prognóstico , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/mortalidade
19.
Pathol Res Pract ; 215(8): 152464, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31176575

RESUMO

BACKGROUND: Accumulating studies reported that 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) may function as either an oncogene or a tumor suppressor in various human cancers. However, its involvement in prostate cancer (PCa) remains unknown. Therefore, the aim of this study was to investigate the clinical significance of HMGCS2 expression and its functions in PCa. METHODS: Expression levels of HMGCS2 mRNA and protein were detected by quantitative Polymerase Chain Reaction (qPCR), Western blot and immunohistochemistry, respectively. Associations of HMGCS2 expression with various clinicopathological features and patients' prognosis of PCa were statistically evaluated. Roles of HMGCS2 dysregulation in cell proliferation, invasion and migration of PCa cell lines were also determined. RESULTS: HMGCS2 protein expression was significantly reduced in PCa tissues compared to adjacent benign prostate tissues at protein levels (P < 0.05). Clinically, low HMGCS2 mRNA expression was dramatically associated with high Gleason score (GS) and pathological grade, as well as the presence of distant metastasis of PCa patients. In addition, PCa patients with low HMGCS2 mRNA expression more frequently had shorter disease-free survival and biochemical recurrence-free survival (all P < 0.05). HMGCS2 expression was identified as an independent factor to predict both disease-free and biochemical recurrence-free survivals of PCa patients. Moreover, loss-of-function experiments demonstrated that HMGCS2 knockdown-expression promotes cell proliferation, colony formation, invasion and migration of PCa cells in vitro and lower the apoptotic rate of PCa cells in vitro. CONCLUSIONS: Our data indicate that HMGCS2 may be capable of predicting the risk of biochemical recurrence in PCa patients after radical prostatectomy and functions as a tumor suppressor in PCa cancer, implying its related pathway potential as a drug candidate in anti-PCa therapy.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Hidroximetilglutaril-CoA Sintase/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Idoso , Biomarcadores Tumorais/metabolismo , Progressão da Doença , Intervalo Livre de Doença , Genes Supressores de Tumor/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Próstata/patologia , Neoplasias da Próstata/diagnóstico
20.
Histopathology ; 75(1): 128-136, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31155736

RESUMO

AIMS: Lymphovascular space invasion (LVSI) in endometrial cancer (EC) is an important prognostic variable impacting on a patient's individual recurrence risk and adjuvant treatment recommendations. Recent work has shown that grading the extent of LVSI further improves its prognostic strength in patients with stage I endometrioid EC. Despite this, there is little information on the reproducibility of LVSI assessment in EC. Therefore, we designed a study to evaluate interobserver agreement in discriminating true LVSI from LVSI mimics (Phase I) and reproducibility of grading extent of LVSI (Phase II). METHODS AND RESULTS: Scanned haematoxylin and eosin (H&E) slides of endometrioid EC (EEC) with a predefined possible LVSI focus were hosted on a website and assessed by a panel of six European gynaecological pathologists. In Phase I, 48 H&E slides were included for LVSI assessment and in Phase II, 42 H&E slides for LVSI grading. Each observer was instructed to apply the criteria for LVSI used in daily practice. The degree of agreement was measured using the two-way absolute agreement average-measures intraclass correlation coefficient (ICC). Reproducibility of LVSI assessment (ICC = 0.64, P < 0.001) and LVSI grading (ICC = 0.62, P < 0.001) in EEC was substantial among the observers. CONCLUSIONS: Given the good reproducibility of LVSI, this study further supports the important role of LVSI in decision algorithms for adjuvant treatment.


Assuntos
Carcinoma Endometrioide/secundário , Neoplasias do Endométrio/patologia , Metástase Linfática/patologia , Carcinoma Endometrioide/patologia , Feminino , Humanos , Metástase Linfática/diagnóstico , Vasos Linfáticos/patologia , Gradação de Tumores/métodos , Invasividade Neoplásica/diagnóstico , Invasividade Neoplásica/patologia , Variações Dependentes do Observador , Prognóstico , Reprodutibilidade dos Testes
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