RESUMO
Inflammation is a common condition of prostate tissue, whose impact on carcinogenesis is highly debated. Microbial colonization is a well-documented cause of a small percentage of prostatitis cases, but it remains unclear what underlies the majority of sterile inflammation reported. Here, androgen- independent fluctuations of PSA expression in prostate cells have lead us to identify a prominent function of the Transient Receptor Potential Cation Channel Subfamily M Member 8 (TRPM8) gene in sterile inflammation. Prostate cells secret TRPM8 RNA into extracellular vesicles (EVs), which primes TLR3/NF-kB-mediated inflammatory signaling after EV endocytosis by epithelial cancer cells. Furthermore, prostate cancer xenografts expressing a translation-defective form of TRPM8 RNA contain less collagen type I in the extracellular matrix, significantly more infiltrating NK cells, and larger necrotic areas as compared to control xenografts. These findings imply sustained, androgen-independent expression of TRPM8 constitutes as a promoter of anticancer innate immunity, which may constitute a clinically relevant condition affecting prostate cancer prognosis.
Assuntos
Neoplasias da Próstata , Canais de Cátion TRPM , Humanos , Masculino , Androgênios , Inflamação/genética , Fator Regulador 3 de Interferon , Proteínas de Membrana , NF-kappa B/genética , Neoplasias da Próstata/genética , Receptor 3 Toll-Like/genética , Canais de Cátion TRPM/genética , AnimaisRESUMO
BACKGROUND & AIMS: The Banff Liver Working Group recently published consensus recommendations for steatosis assessment in donor liver biopsy, but few studies reported their use and no automated deep-learning algorithms based on the proposed criteria have been developed so far. We evaluated Banff recommendations on a large monocentric series of donor liver needle biopsies by comparing pathologists' scores with those generated by convolutional neural networks (CNNs) we specifically developed for automated steatosis assessment. METHODS: We retrospectively retrieved 292 allograft liver needle biopsies collected between January 2016 and January 2020 and performed steatosis assessment using a former intra-institution method (pre-Banff method) and the newly introduced Banff recommendations. Scores provided by pathologists and CNN models were then compared, and the degree of agreement was measured with the intraclass correlation coefficient (ICC). RESULTS: Regarding the pre-Banff method, poor agreement was observed between the pathologist and CNN models for small droplet macrovesicular steatosis (ICC: 0.38), large droplet macrovesicular steatosis (ICC: 0.08), and the final combined score (ICC: 0.16) evaluation, but none of these reached statistically significance. Interestingly, significantly improved agreement was observed using the Banff approach: ICC was 0.93 for the low-power score (p <0.001), 0.89 for the high-power score (p <0.001), and 0.93 for the final score (p <0.001). Comparing the pre-Banff method with the Banff approach on the same biopsy, pathologist and CNN model assessment showed a mean (±SD) percentage of discrepancy of 26.89 (±22.16) and 1.20 (±5.58), respectively. CONCLUSIONS: Our findings support the use of Banff recommendations in daily practice and highlight the need for a granular analysis of their effect on liver transplantation outcomes. IMPACT AND IMPLICATIONS: We developed and validated the first automated deep-learning algorithms for standardized steatosis assessment based on the Banff Liver Working Group consensus recommendations. Our algorithm provides an unbiased automated evaluation of steatosis, which will lay the groundwork for granular analysis of steatosis's short- and long-term effects on organ viability, enabling the identification of clinically relevant steatosis cut-offs for donor organ acceptance. Implementing our algorithm in daily clinical practice will allow for a more efficient and safe allocation of donor organs, improving the post-transplant outcomes of patients.
Assuntos
Aprendizado Profundo , Fígado Gorduroso , Transplante de Fígado , Humanos , Consenso , Estudos Retrospectivos , Doadores Vivos , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/patologia , Biópsia , AlgoritmosRESUMO
Temporomandibular disorders (TMDs) refer to a group of conditions that affect the temporomandibular joint, causing pain and dysfunction in the jaw joint and related muscles. The diagnosis of TMDs typically involves clinical assessment through operator-based physical examination, a self-reported questionnaire and imaging studies. To objectivize the measurement of TMD, this study aims at investigating the feasibility of using machine-learning algorithms fed with data gathered from low-cost and portable instruments to identify the presence of TMD in adult subjects. Through this aim, the experimental protocol involved fifty participants, equally distributed between TMD and healthy subjects, acting as a control group. The diagnosis of TMD was performed by a skilled operator through the typical clinical scale. Participants underwent a baropodometric analysis by using a pressure matrix and the evaluation of the cervical mobility through inertial sensors. Nine machine-learning algorithms belonging to support vector machine, k-nearest neighbours and decision tree algorithms were compared. The k-nearest neighbours algorithm based on cosine distance was found to be the best performing, achieving performances of 0.94, 0.94 and 0.08 for the accuracy, F1-score and G-index, respectively. These findings open the possibility of using such methodology to support the diagnosis of TMDs in clinical environments.
Assuntos
Algoritmos , Aprendizado de Máquina , Transtornos da Articulação Temporomandibular , Humanos , Transtornos da Articulação Temporomandibular/diagnóstico , Transtornos da Articulação Temporomandibular/fisiopatologia , Masculino , Feminino , Adulto , Máquina de Vetores de Suporte , Pessoa de Meia-Idade , Adulto Jovem , Árvores de DecisõesRESUMO
PURPOSE: Transperineal mpMRI-targeted fusion prostate biopsies (TPFBx) are recommended for prostate cancer diagnosis, but little is known about their learning curve (LC), especially when performed under local anaesthesia (LA). We investigated how operators' and institutions' experience might affect biopsy results. METHODS: Baseline, procedure and pathology data of consecutive TPFBx under LA were prospectively collected at two academic Institutions, from Sep 2016 to May 2019. Main inclusion criterion was a positive MRI. Endpoints were biopsy duration, clinically significant prostate cancer detection rate on targeted cores (csCDR-T), complications, pain and urinary function. Data were analysed per-centre and per-operator (with ≥ 50 procedures), comparing groups of consecutive patient, and subsequently through regression and CUSUM analyses. Learning curves were plotted using an adjusted lowess smoothing function. RESULTS: We included 1014 patients, with 27.3% csCDR-T and a median duration was 15 min (IQR 12-18). A LC for biopsy duration was detected, with the steeper phase ending after around 50 procedures, in most operators. No reproducible evidence in favour of an impact of experience on csPCa detection was found at operator's level, whilst a possible gentle LC of limited clinical relevance emerged at Institutional level; complications, pain and IPSS variations were not related to operator experience. CONCLUSION: The implementation of TPFBx under LA was feasible, safe and efficient since early phases with a relatively short learning curve for procedure time.
Assuntos
Imagem por Ressonância Magnética Intervencionista , Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Curva de Aprendizado , Anestesia Local , Estudos Prospectivos , Imagem por Ressonância Magnética Intervencionista/métodos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética/métodos , DorRESUMO
The importance of physical activity has been widely demonstrated both in clinics and in sports. One of the new frontier training programs is high-intensity functional training (HIFT). The immediate effects of HIFT on the psychomotor and cognitive performance of well-trained people are still not clear. This paper aims to evaluate the immediate effects induced by HIFT on blood lactate levels, physical performance in terms of body stability and jump ability, and cognitive performance in terms of reaction time. Nineteen well-trained participants were enrolled in the experimental studies and asked to execute six repetitions of a circuit training. Data were gathered both in a pre-training session and after each one of the circuit repetitions. An immediate significant increase with respect to the baseline was observed during the first repetition, with a further increase after the third one. No effects on jump ability were found, whereas a deterioration in body stability was found. Positive immediate effects on cognitive performance in terms of accuracy and speed in task execution were assessed. The findings can be exploited by trainers during coaching to optimize the design of training programs.
Assuntos
Treinamento Intervalado de Alta Intensidade , Esportes , Humanos , Adulto , Exercício Físico , CogniçãoRESUMO
OBJECTIVE: To assess the outcomes of multiparametric magnetic resonance imaging (mpMRI) transperineal targeted fusion biopsy (TPFBx) under local anaesthesia. PATIENTS AND METHODS: We prospectively screened 1327 patients with a positive mpMRI undergoing TPFBx (targeted cores and systematic cores) under local anaesthesia, at two tertiary referral institutions, between September 2016 and May 2019, for inclusion in the present study. Primary outcomes were detection of clinically significant prostate cancer (csPCa) defined as (1) International Society of Urological Pathologists (ISUP) grade >1 or ISUP grade 1 with >50% involvement of prostate cancer (PCa) in a single core or in >2 cores (D1) and (2) ISUP grade >1 PCa (D2). Secondary outcomes were: assessment of peri-procedural pain (numerical rating scale [NRS]) and procedure timings; erectile (International Index of Erectile Function) and urinary (International Prostate Symptom Score) function changes; and complications. We also investigated the value of systematic sampling and concordance with radical prostatectomy (RP). RESULTS: A total of 1014 patients were included, of whom csPCa was diagnosed in 39.4% (n = 400). The procedure was tolerable (NRS pain score 3.1 ± 2.3), with no impact on erectile (P = 0.45) or urinary (P = 0.58) function, and a low rate of complications (Clavien-Dindo grades 1 or 2, n = 8; grade >2, n = 0). No post-biopsy sepsis was recorded. Twenty-two men (95% confidence interval [CI] 17-29) needed to undergo additional systematic biopsy to diagnose one csPCa missed by targeted biopsies (D1). ISUP grade concordance of biopsies with RP was as follows: k = 0.40 (95% CI 0.31-0.49) for targeted cores alone and k = 0.65 (95% CI 0.57-0.72; P < 0.05) overall. CONCLUSIONS: The use of TPFBx under local anaesthesia yielded good csPCa detection and was feasible, quick, well tolerated and safe. Infectious risk was negligible. Addition of systematic to targeted cores may not be needed in all men, although it improves csPCa detection and concordance with RP.
Assuntos
Anestesia Local , Biópsia com Agulha de Grande Calibre/métodos , Biópsia Guiada por Imagem/métodos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Biópsia com Agulha de Grande Calibre/efeitos adversos , Hematúria/etiologia , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Complicações Intraoperatórias/etiologia , Masculino , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética Multiparamétrica , Dor Pós-Operatória/etiologia , Ereção Peniana , Períneo , Estudos Prospectivos , MicçãoRESUMO
Anterior cruciate ligament (ACL) injury represents one of the main disorders affecting players, especially in contact sports. Even though several approaches based on artificial intelligence have been developed to allow the quantification of ACL injury risk, their applicability in training sessions compared with the clinical scale is still an open question. We proposed a machine-learning approach to accomplish this purpose. Thirty-nine female basketball players were enrolled in the study. Leg stability, leg mobility and capability to absorb the load after jump were evaluated through inertial sensors and optoelectronic bars. The risk level of athletes was computed by the Landing Error Score System (LESS). A comparative analysis among nine classifiers was performed by assessing the accuracy, F1-score and goodness. Five out nine examined classifiers reached optimum performance, with the linear support vector machine achieving an accuracy and F1-score of 96 and 95%, respectively. The feature importance was computed, allowing us to promote the ellipse area, parameters related to the load absorption and the leg mobility as the most useful features for the prediction of anterior cruciate ligament injury risk. In addition, the ellipse area showed a strong correlation with the LESS score. The results open the possibility to use such a methodology for predicting ACL injury.
Assuntos
Lesões do Ligamento Cruzado Anterior , Basquetebol , Lesões do Ligamento Cruzado Anterior/diagnóstico , Inteligência Artificial , Atletas , Feminino , Humanos , Aprendizado de MáquinaRESUMO
The possibility of measuring predictive factors to discriminate athletes at higher risk of anterior cruciate ligament (ACL) injury still represents an open research question. We performed an observational study with thirteen female basketball players who performed monopodalic jumps and single-leg squat tests. One of them suffered from an ACL injury after the first test session. Data gathered from twelve participants, who did not suffer from ACL injury, were used for a reliability analysis. Parameters related to leg stability, load absorption capability and leg mobility showed good-to-excellent reliability. Path length, root mean square of the acceleration and leg angle with respect to the vertical axis revealed themselves as possible predictive factors to identify athletes at higher risk. Results confirm that six months after reconstruction represents the correct time for these athletes to return to playing. Furthermore, the training of leg mobility and load absorption capability could allow athletes to reduce the probability of new injuries.
Assuntos
Lesões do Ligamento Cruzado Anterior , Basquetebol , Lesões do Ligamento Cruzado Anterior/diagnóstico , Atletas , Feminino , Humanos , Reprodutibilidade dos TestesRESUMO
PURPOSE: Several transperineal biopsy series have proven feasibility under local anesthesia. However, there is a lack of large analyses detailing pain outcomes and factors influencing pain. MATERIALS AND METHODS: From 2016 to 2019 we performed a multicenter prospective study in men undergoing multiparametric magnetic resonance imaging-transperineal fusion biopsies (target+systematic cores) under local anesthesia. Primary outcomes were 1) pain scores (assessed through a 0 to 10-point numeric rating scale) and 2) identification of factors associated with severe pain. The secondary outcome was to evaluate pain influence on clinically significant prostate cancer target cores detection. RESULTS: We included 1,008 men undergoing transperineal fusion biopsies under local anesthesia. Mean±SD numeric rating scale pain scores were 3.9±2.1 at local anesthesia administration and 3.1±2.3 when performing biopsies. Pain was not associated with lower clinically significant prostate cancer detection on targeted cores (p=0.23 and p=0.47 depending on clinically significant prostate cancer definition). On multivariate analysis age (OR 0.96, 95% CI 0.94-0.99) and severe anxiety (OR 2.99, 95% CI 1.83-4.89) were a protective and risk factor, respectively, for severe biopsy pain. Procedural time was also associated with an increased risk of experiencing severe biopsy pain (OR 1.04, 95% CI 1.00-1.08). If aiming to test the possible effects of anxiety preventive measures on pain, an anxiety cutoff greater than 6 on a numeric rating scale would decrease to 13% the number of patients being treated while identifying 56% of those experiencing severe pain. CONCLUSIONS: Transperineal fusion biopsies under local anesthesia result in moderate pain. Pain does not influence clinically significant prostate cancer target detection. Patient anxiety predicts pain. A numeric rating scale based anxiety assessment may be used to identify those at higher risk for experiencing severe pain in men undergoing transperineal fusion biopsies.
Assuntos
Anestesia Local , Ansiedade/epidemiologia , Dor Processual/epidemiologia , Neoplasias da Próstata/diagnóstico , Idoso , Ansiedade/diagnóstico , Ansiedade/etiologia , Ansiedade/psicologia , Biópsia com Agulha de Grande Calibre/efeitos adversos , Biópsia com Agulha de Grande Calibre/métodos , Biópsia com Agulha de Grande Calibre/psicologia , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Biópsia Guiada por Imagem/métodos , Biópsia Guiada por Imagem/psicologia , Imagem por Ressonância Magnética Intervencionista , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Imageamento por Ressonância Magnética Multiparamétrica , Medição da Dor , Dor Processual/diagnóstico , Dor Processual/etiologia , Dor Processual/prevenção & controle , Períneo/cirurgia , Estudos Prospectivos , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/patologia , Medição de Risco/métodos , Fatores de Risco , Ultrassonografia de IntervençãoRESUMO
Pulmonary lymphoid lesions span from benign to other forms of malignant diseases. Among these pulmonary lymphoid lesions, Nodular Lymphoid Hyperplasia (NLH) has an excellent prognosis. The surgical excision of NLH seems to be the only treatment, even if in some cases a spontaneous regression has been reported. Interestingly, these lesions may have similar clinical and radiographic presentations, making a histopathological examination vital for their differentiation. In this report we describe four cases of pediatric patients with a previous history of classical Hodgkin Lymphoma (HL) with documented or suspected NLH.
Assuntos
Doença de Hodgkin/complicações , Pneumopatias/complicações , Linfócitos/patologia , Pseudolinfoma/complicações , Adolescente , Criança , Feminino , Humanos , Hiperplasia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pneumopatias/diagnóstico , Masculino , Prognóstico , Pseudolinfoma/diagnóstico , Remissão Espontânea , Tomografia Computadorizada por Raios XRESUMO
This study aimed at assessing physical performance of elite karatekas and non-karatekas. More specifically, effects of kumite and kata technique on joint mobility, body stability, and jumping ability were assessed by enrolling twenty-four karatekas and by comparing the results with 18 non-karatekas healthy subjects. Sensor system was composed by a single inertial sensor and optical bars. Karatekas are generally characterized by better motor performance with respect nonkaratekas, considering all the examined factors, i.e., mobility, stability, and jumping. In addition, the two techniques lead to a differentiation in joint mobility; in particular, kumite athletes are characterized by a greater shoulder extension and, in general, by a greater value of preferred velocity to perform joint movements. Conversely, kata athletes are characterized by a greater mobility of the ankle joint. By focusing on jumping skills, kata technique leads to an increase of the concentric phase when performing squat jump. Finally, kata athletes showed better stability inclosed eyes condition. The outcomes reported here can be useful for optimizing coaching programs for both beginners and karatekas based on the specific selected technique.
Assuntos
Atletas , Desempenho Atlético , Artes Marciais , Humanos , Movimento , Amplitude de Movimento ArticularRESUMO
In this paper, we describe the Prognostic Factors for Mortality in Prostate Cancer (ProMort) study and use it to demonstrate how the weighted likelihood method can be used in nested case-control studies to estimate both relative and absolute risks in the competing-risks setting. ProMort is a case-control study nested within the National Prostate Cancer Register (NPCR) of Sweden, comprising 1,710 men diagnosed with low- or intermediate-risk prostate cancer between 1998 and 2011 who died from prostate cancer (cases) and 1,710 matched controls. Cause-specific hazard ratios and cumulative incidence functions (CIFs) for prostate cancer death were estimated in ProMort using weighted flexible parametric models and compared with the corresponding estimates from the NPCR cohort. We further drew 1,500 random nested case-control subsamples of the NPCR cohort and quantified the bias in the hazard ratio and CIF estimates. Finally, we compared the ProMort estimates with those obtained by augmenting competing-risks cases and by augmenting both competing-risks cases and controls. The hazard ratios for prostate cancer death estimated in ProMort were comparable to those in the NPCR. The hazard ratios for dying from other causes were biased, which introduced bias in the CIFs estimated in the competing-risks setting. When augmenting both competing-risks cases and controls, the bias was reduced.
Assuntos
Neoplasias da Próstata/mortalidade , Fatores Etários , Idoso , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Antígeno Prostático Específico , Neoplasias da Próstata/terapia , Medição de Risco , Fatores de Risco , Suécia/epidemiologiaRESUMO
BACKGROUND: Several studies in the past have investigated the expression of micro RNAs (miRNAs) in saliva as potential biomarkers. Since miRNAs associated with extracellular vesicles (EVs) are known to be protected from enzymatic degradation, we evaluated whether salivary EVs from patients with oral squamous cell carcinoma (OSCC) were enriched with specific subsets of miRNAs. METHODS: OSCC patients and controls were matched with regards to age, gender and risk factors. Total RNA was extracted from salivary EVs and the differential expression of miRNAs was evaluated by qRT-PCR array and qRT-PCR. The discrimination power of up-regulated miRNAs as biomarkers in OSCC patients versus controls was evaluated by the Receiver Operating Characteristic (ROC) curves. RESULTS: A preliminary qRT-PCR array was performed on samples from 5 OSCC patients and 5 healthy controls whereby a subset of miRNAs were identified that were differentially expressed. On the basis of these results, a cohort of additional 16 patients and 6 controls were analyzed to further confirm the miRNAs that were up-regulated or selectively expressed in the previous pilot study. The following miRNAs: miR-302b-3p and miR-517b-3p were expressed only in EVs from OSCC patients and miR-512-3p and miR-412-3p were up-regulated in salivary EVs from OSCC patients compared to controls with the ROC curve showing a good discrimination power for OSCC diagnosis. The Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis suggested the possible involvement of the miRNAs identified in pathways activated in OSCC. CONCLUSIONS: In this work, we suggest that salivary EVs isolated by a simple charge-based precipitation technique can be exploited as a non-invasive source of miRNAs for OSCC diagnosis. Moreover, we have identified a subset of miRNAs selectively enriched in EVs of OSCC patients that could be potential biomarkers.
Assuntos
Carcinoma de Células Escamosas/genética , Vesículas Extracelulares/metabolismo , MicroRNAs/genética , Neoplasias Bucais/genética , Saliva/metabolismo , Adulto , Idoso , Biomarcadores , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Feminino , Papillomavirus Humano 16 , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Neoplasias Bucais/virologia , Estadiamento de Neoplasias , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologiaAssuntos
Carcinoma de Célula de Merkel , Síndrome Miastênica de Lambert-Eaton , Neoplasias Pulmonares , Neoplasias Primárias Desconhecidas , Degeneração Paraneoplásica Cerebelar , Síndromes Paraneoplásicas , Neoplasias Cutâneas , Carcinoma de Célula de Merkel/diagnóstico , Humanos , Síndrome Miastênica de Lambert-Eaton/diagnóstico , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/etiologia , Neoplasias Cutâneas/complicaçõesRESUMO
OBJECTIVE: Stereotactic ablative radiotherapy (SABR) is a safe treatment approach for hepatocellular carcinoma (HCC) with comparable effectiveness to other local therapies. Only scant information is available concerning the role of SABR prior to liver transplantation (LT) for HCC. We present a consecutive case series investigating the role of SABR as a bridge or downstaging option in HCC patients subsequently submitted to LT. MATERIALS AND METHODS: Between September 2012 and May 2014, 8 patients for a total of 13 lesions underwent SABR prior to LT. Inclusion criteria were a pathological or radiological diagnosis of HCC, lesion size ≤6 cm or lesion number ≤3 with a total diameter ≤6 cm, no extrahepatic metastases, Child-Pugh class A-B, ECOG performance status ≤1. Patients were prescribed 36-48 Gy in 3-5 fractions (8 Gy × 5 fractions or 16 Gy × 3 fractions), in 3-5 consecutive days according to clinical and dosimetric decision making. Radiological response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Pathological response was assessed through the rate of tumor necrosis relative to the total tumor volume. Acute and late toxicities were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4 (CTCAE v 4.0). RESULTS: Among the 13 pathologically evaluated lesions, 8 (61.5 %) lesions had a complete response 2 (15.3 %) had a minimal pathological response and other 2 (15.3 %) showed stable disease. The remaining lesion had a significant pathological response. Maximum detected toxicity included a G2 GGT increase in two patients (at 1 and 3 months respectively). One patient developed a non-classic RILD with a fivefold increase in transaminase enzymes level and a shift in Child-Pugh category from B7 to C10 due to bilirubin increase. Only one modification in the surgical strategy was needed during LT. CONCLUSIONS: SABR proved to be a safe and effective local therapy prior to LT in HCC patients. Prospective controlled clinical trials are needed to evaluate its efficacy compared to other local therapies in this setting.
Assuntos
Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Fracionamento da Dose de Radiação , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Técnicas Estereotáxicas , Resultado do Tratamento , Carga TumoralRESUMO
Mitotic count on hematoxylin and eosin slides is a fundamental morphological criterion in the diagnosis and grading of adrenocortical carcinoma in any scoring system employed. Moreover, it is the unique term strongly associated with patient's prognosis. Phospho-histone H3 is a mitosis-specific antibody, which was already proven to facilitate mitotic count in melanoma and other tumors. Therefore, a study was designed to assess the diagnostic and prognostic role of phospho-histone H3 in 52 adrenocortical carcinomas, comparing manual and computerized count to standard manual hematoxylin- and eosin-based method and Ki-67 index. Manual hematoxylin and eosin and phospho-histone H3 mitotic counts were highly correlated (r=0.9077, P<0.0001), better than computer-assisted phospho-histone H3 evaluations, and had an excellent inter-observer reproducibility at Bland-Altman analysis. Three of 15 cases having <5 mitotic figures per 50 high-power fields by standard count on hematoxylin and eosin gained the mitotic figure point of Weiss Score after a manual count on phospho-histone H3 slides. Traditional mitotic count confirmed to be a strong predictor of overall survival (P=0.0043), better than phospho-histone H3-based evaluation (P=0.051), but not as strong as the Ki-67 index (P<0.0001). The latter further segregated adrenocortical carcinomas into three prognostic groups, stratifying cases by low (<20%), intermediate (20-50%), and high (>50%) Ki-67 values. We conclude that (a) phospho-histone H3 staining is a useful diagnostic complementary tool to standard hematoxylin and eosin mitotic count, enabling optimal mitotic figure evaluation (including atypical mitotic figures) even in adrenocortical carcinomas with a low mitotic index and with a very high reproducibility; (b) Ki-67 proved to be the best prognostic indicator of overall survival, being superior to the mitotic index, irrespective of the method (standard on hematoxylin and eosin or phospho-histone H3-based) used to count mitotic figures.
Assuntos
Neoplasias do Córtex Suprarrenal/metabolismo , Carcinoma Adrenocortical/metabolismo , Histonas/metabolismo , Antígeno Ki-67/metabolismo , Índice Mitótico , Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/mortalidade , Carcinoma Adrenocortical/patologia , Adulto , Idoso , Amarelo de Eosina-(YS) , Feminino , Hematoxilina , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Fosforilação , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
A subgroup of HER2-overexpressing breast tumours co-expresses p95(HER2), a truncated HER2 receptor that retains a functional HER2 kinase domain but lacks the extracellular domain, thus impairing trastuzumab binding. We evaluated p95(HER2) expression in 99 frozen breast carcinoma samples by western blot analysis. The HER2-positive cell line BT474 treated with pervanadate or pronase was used as a positive control for p95(HER2) expression. Immunohistochemistry was performed on parallel formalin-fixed, paraffin-embedded sections of the same case series using antibodies directed against either the intra- or extra-cellular binding domain of HER2. In particular, biotinylated trastuzumab (BiotHER) was used to evaluate the binding capacity of the humanized antibody. To avoid a subjective evaluation of the score values and the percentage of immunostained cells, the slides were scanned and automatically analysed. The number of cases with HER2 overexpression (score 3+) and HER2 gene amplification was higher in the p185(HER2)-positive/p95(HER2)-positive samples than in the p185(HER2)-positive/p95(HER2)-negative group. Automated analysis confirmed a significantly higher percentage of 3+ scored cells in p95(HER2)-positive cases. Conversely, the percentage of 2+ scored cells was higher inp95(HER2)-negative cases. The status of the HER2 extracellular domain was then studied using flow cytometry on BT474 cells after pronase enzymatic digestion using trastuzumab and pertuzumab, while the presence of HER2-HER3 dimers was studied using a proximity-ligation assay. In vitro experiments showed that short-term pronase digestion of BT474 cells produced two HER2 fragments (of 95 and 150 kDa, detectable in tissue specimens as well), increased the binding affinity of trastuzumab, reduced the rate of HER2-HER3 dimers, and did not interfere with pertuzumab-binding capacity. In conclusion, the presence of p95(HER2 as detected by western blot analysis does not compromise the immunohistochemical detection of HER2. Our data suggest that a reduction of the receptor steric hindrance as induced by enzymatic shedding may facilitate the binding capacity of trastuzumab.
Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Pronase/farmacologia , Receptor ErbB-2/metabolismo , Anticorpos Monoclonais Humanizados/metabolismo , Antineoplásicos/metabolismo , Western Blotting , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , DNA de Neoplasias/análise , Inibidores Enzimáticos/farmacologia , Feminino , Citometria de Fluxo , Humanos , Hibridização in Situ Fluorescente , Pronase/antagonistas & inibidores , Ligação Proteica , Trastuzumab , Vanadatos/farmacologiaRESUMO
CONTEXT: Primary venous leiomyosarcoma (LMS) is a rare disease, most commonly affecting the retroperitoneal veins and in particular the inferior vena cava. Five-year survival rate ranges between 33% and 68%. CASE REPORT: Complete surgical resection represents the only potentially curative treatment, occasionally achieving long-term survival. LMS of the splenic vein is extremely rare, with only three cases reported in the literature. CONCLUSION: We report a case of primary venous LMS arising from the splenic vein and we briefly review the relevant literature.
RESUMO
Localized nasal argyria has been reported in 3 published articles as secondary to occupational exposure and involving the anterior part of the nose. No previous cases of such pathology involving the rhinopharynx were described. Here we report the first case of localized argyria of the roof and of the posterior wall of the rhinopharynx secondary to prolonged use of nasal drops containing colloidal silver protein. The recognition of such pathology can be useful to increase the number of conditions that must be considered in the differential diagnosis of rhinopharyngeal mucosa alterations.
Assuntos
Argiria/diagnóstico , Argiria/etiologia , Hidrogéis/administração & dosagem , Hidrogéis/efeitos adversos , Doenças Nasofaríngeas/induzido quimicamente , Doenças Nasofaríngeas/diagnóstico , Compostos de Prata/administração & dosagem , Compostos de Prata/efeitos adversos , Administração Intranasal/efeitos adversos , Argiria/patologia , Feminino , Humanos , Hipertrofia/patologia , Doença Iatrogênica , Pessoa de Meia-Idade , Nasofaringe/patologiaRESUMO
BACKGROUND: Relapse and refractory (R/R) rates after first-line R-CHOP in diffuse large B cell lymphomas (DLBCL) are ~40% and ~15% respectively. AIMS: We conducted a retrospective real-world analysis aimed at evaluating clinical outcomes of R/R DLBCL patients. MATERIAL AND METHODS: Overall, 403 consecutive DLBCL patients treated in two large hematological centers in Torino, Italy were reviewed. RESULTS: At a median follow up of 50 months, 5-year overall survival from diagnosis (OS-1) was 66.5%, and 2-year progression free survival (PFS-1) was 68%. 134 (34.4%) patients relapsed (n = 46, 11.8%) or were refractory (n = 88, 22.6%) to R-CHOP. Most employed salvage treatments included platinum salt-based regimens in 38/134 (28.4%), lenalidomide in 14 (10.4%). Median OS and PFS after disease relapse or progression (OS-2 and PFS-2) were 6.7 and 5.1 months respectively. No significant difference in overall response rate, OS-2 or PFS-2 in patients treated with platinum-based regimens versus other regimens was observed. By multivariate analysis, age between 60 and 80 years, germinal center B cell type cell of origin and extranodal involvement of <2 sites were associated with better OS-2. DISCUSSION: Our findings confirm very poor outcomes of R/R DLBCL in the rituximab era. Widespread approval by national Medicine Agencies of novel treatments such as CAR-T cells and bispecific antibodies as second-line is eagerly awaited to improve these outcomes.