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1.
Am J Surg Pathol ; 44(4): 545-552, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31917707

RESUMO

Polymorphous adenocarcinoma (PAC) shows histologic diversity with streaming and targetoid features whereas cribriform adenocarcinoma of salivary gland (CASG) demonstrates predominantly cribriform and solid patterns with glomeruloid structures and optically clear nuclei. Opinions diverge on whether CASG represents a separate entity or a variant of PAC. We aimed to assess the level of agreement among 25 expert Head and Neck pathologists in classifying these tumors. Digital slides of 48 cases were reviewed and classified as: PAC, CASG, tumors with ≥50% of papillary architecture (PAP), and tumors with indeterminate features (IND). The consensus diagnoses were correlated with a previously reported molecular alteration. The consensus diagnoses were PAC in 18/48, CASG in16/48, PAP in 3/48, and IND in 11/48. There was a fair interobserver agreement in classifying the tumors (κ=0.370). The full consensus was achieved in 3 (6%) cases, all of which were classified as PAC. A moderate agreement was reached for PAC (κ=0.504) and PAP (κ=0.561), and a fair agreement was reached for CASG (κ=0.390). IND had only slight diagnostic concordance (κ=0.091). PAC predominantly harbored PRKD1 hotspot mutation, whereas CASG was associated with fusion involving PRKD1, PRKD2, or PRKD3. However, such molecular events were not exclusive as 7% of PAC had fusion and 13% of CASG had mutation. In conclusion, a fair to moderate interobserver agreement can be achieved in classifying PAC and CASG. However, a subset (23%) showed indeterminate features and was difficult to place along the morphologic spectrum of PAC/CASG among expert pathologists. This may explain the controversy in classifying these tumors.

3.
Am J Clin Pathol ; 153(1): 74-81, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31415691

RESUMO

OBJECTIVES: This study aimed to determine whether Ki-67 index evaluated on cytologic material could reliably grade pancreatic neuroendocrine tumors (PanNETs). METHODS: Cases with adequate cell block and available surgical specimens were included. Ki-67 index was calculated using "eyeballing," "hot spot," and "complete" counting methods. RESULTS: The overall concordance rates between cytology and surgical specimens were 71%, 73%, and 59%, respectively, by using eyeballing, hot spot, and complete counting approaches. All grade 1 tumors were correctly graded on cytology, but in grade 2 tumors concordance rates were only 36%, 41%, and 9%, respectively. All grade 2 tumors were undergraded when cell blocks contained fewer than 1,000 cells, while concordance rate increased to 57%, 64%, and 14%, respectively, in cases with 1,000 cells or more. CONCLUSIONS: Grade 2 PanNETs can be significantly undergraded when Ki-67 index is evaluated on cell block material. In cases with 1,000 or more cells, the hot spot counting method has better correlation with surgical specimens.

4.
Sleep Breath ; 2019 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-31836994

RESUMO

PURPOSE: Non-resective pharyngoplasty techniques have been shown to be effective to treat oropharyngeal collapse in patients affected by obstructive sleep apnea-hypopnea syndrome (OSAHS). The aim of our study is to evaluate outcome predictors in a cohort of patients affected by OSAHS and treated with non-resective pharyngoplasty, including variation of pharyngeal measures at the end of the surgical procedure. METHODS: A cohort of patients affected by OSAHS, with palatal or lateral pharyngeal wall collapse, who underwent non-resective pharyngoplasty, were enrolled between 2014 and 2017. Surgical procedures encompassed non-resective pharyngoplasty by expansion sphincter pharyngoplasty (ESP) or barbed antero-lateral pharyngoplasty with barbed reposition pharyngoplasty (BRP) or barbed suspension pharyngoplasty (BSP) techniques, eventually associated with nasal surgery. Pharyngeal measures were recorded intraoperatively and their variation at the end of the procedure was considered. Surgical success was evaluated at least 6 months after surgery with respiratory polygraphy and ESS questionnaire. Outcome predictors were examined by multivariable logistic regression and ROC curve analysis. RESULTS: Seventy patients met the study inclusion criteria. ESP, BRP, and BSP in a uni-/multilevel setting led to significant improvement of all respiratory polygraphic parameters and daily sleepiness (p < 0.0001). Outcome analysis showed that greater variation of antero-posterior pharyngeal measure was associated with success (p = 0.01), with an optimal cutoff value of 8.5 mm; low AHIpre, high ESSpre, and antero-lateral pharyngoplasty with barbed sutures were associated with a higher rate of cure (p < 0.05). CONCLUSIONS: Non-resective pharyngoplasty is effective in treating OSAHS patients affected by palatal or lateral pharyngeal wall collapse, and intraoperative variation of antero-posterior width may be a useful tool to predict surgical success.

5.
Surg Pathol Clin ; 12(4): 1021-1044, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31672292

RESUMO

Neuroendocrine neoplasms (NENs) of the gastrointestinal (GI) tract and pancreas are a rare and heterogeneous group of neoplasms characterized by common cellular features as well as unique site-specific traits. GI and pancreatic NENs are much rarer than the more common adenocarcinomas arising at these sites. However, the incidences of GI and pancreatic NENs have increased significantly, particularly in the stomach and common site, followed by rectum, appendix, colon, and stomach. Pancreatic NENs are also uncommon, with fewer than 1 per 100,000, accounting for 1% to 2% of all pancreatic neoplasms.

6.
Expert Rev Cardiovasc Ther ; 17(9): 653-662, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31483165

RESUMO

Introduction: Despite current guidelines provide recommendations for the optimal management of degenerative mitral regurgitation (MR), this condition remains often undertreated with delay in surgical referral and dismal effect on outcomes. Areas covered: This review focuses on the role of echocardiography in guiding mitral valve (MV) surgical repair in degenerative MR due to leaflet prolapse. Expert opinion: A stepwise protocol-driven echocardiography shared by referring physician and surgeon may help to guide referral to surgical repair in degenerative MR. This protocol particularly is useful to identify the ideal patho-anatomy for a successful and durable repair especially when early surgery is proposed and to refer the patient to centers of excellence in case of complex anatomy. Nearly 100% repair rate can be achieved when the surgical technique is adapted to the lesions seen in each valve. Three-dimensional echocardiography predicts repair complexity may be useful and should therefore be implemented. However, the current literature is far from comprehensive deriving from small, single-center studies. Therefore, reproducibility and external validation, especially with newly developed quantitative automated software, are still needed.


Assuntos
Ecocardiografia Tridimensional/métodos , Insuficiência da Valva Mitral/cirurgia , Prolapso da Valva Mitral/cirurgia , Procedimentos Cirúrgicos Cardíacos/métodos , Ecocardiografia/métodos , Humanos , Reprodutibilidade dos Testes
7.
J Craniofac Surg ; 30(5): 1503-1505, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31299754

RESUMO

Rhinogenic headache (RH) is a widespread pain syndrome but its pathogenesis and treatment are still unclear. Some authors recognize a correlation between RH and mucosal contact points or some other sinonasal anatomical variations. The authors conducted a retrospective case-control study to analyze the correlation between radiological findings and clinical symptoms.One hundred-nineteen adults with Para-Nasal Sinuses Computed Tomography (PNS-CT) scans were included: 64 patients who have originally undergone PNS-CT scan as part of rhinogenic headache workup (Group A), and 55 controls in whom PNS-CT scans were obtained for other purposes (Group B). All subjects were asked to report their symptoms using a headache scoring system. PNS-CT scans of all subjects were analyzed for presence of mucosal contact points, middle turbinate concha bullosa (MTCB) and frontoethmoidal cells.The most common anatomical abnormality found in our series was MTCB, reported in 60.9% of patients in Group A and 41.8% of those in Group B. A statistically significant prevalence was found in Group A compared to Group B regarding the presence of MTCB (P = 0.037) and Type II (P = 0.016) and Type III (P = 0.039) frontoethmoidal cells. No statistically significant difference (P >0.05) was found between Group A and Group B regarding the presence of mucosal contact points at each site.Multiple anatomical variations in nasal and paranasal sinuses may cause a rhinogenic headache with different characteristics. Some of these, such as concha bullosa of middle turbinate or type II and III Kuhn cells, have shown a significant association with rhinogenic headache. No statistically significant association was found between presence of headache and mucosal contact points and type I and IV frontal cells. These findings can be very helpful for the surgeons that want to deal with the treatment of RH.


Assuntos
Cefaleia/etiologia , Doenças Nasais/complicações , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seios Paranasais , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/efeitos adversos , Adulto Jovem
8.
Front Immunol ; 10: 1092, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31156639

RESUMO

Chemokine receptor CXCR4, its ligand stromal cell-derived factor-1 (CXCL12) and the decoy receptor atypical chemokine receptor 3 (ACKR3, also named CXCR7), are involved in the guidance of migrating cells in different anatomical districts. Here, we investigated the role of the ACKR3 zebrafish ortholog ackr3b in the vascularization process during embryonic development. Bioinformatics and functional analyses confirmed that ackr3b is a CXCL12-binding ortholog of human ACKR3. ackr3b is transcribed in the endoderm of zebrafish embryos during epiboly and is expressed in a wide range of tissues during somitogenesis, including central nervous system and somites. Between 18 somite and 26 h-post fertilization stages, the broad somitic expression of ackr3b becomes restricted to the basal part of the somites. After ackr3b knockdown, intersomitic vessels (ISVs) lose the correct direction of migration and are characterized by the presence of aberrant sprouts and ectopic filopodia protrusions, showing downregulation of the tip/stalk cell marker hlx1. In addition, ackr3b morphants show significant alterations of lateral dorsal aortae formation. In keeping with a role for ackr3b in endothelial cell guidance, CXCL12 gradient generated by ACKR3 expression in CHO cell transfectants guides human endothelial cell migration in an in vitro cell co-culture chemotaxis assay. Our results demonstrate that ackr3b plays a non-redundant role in the guidance of sprouting endothelial cells during vascular development in zebrafish. Moreover, ACKR3 scavenging activity generates guidance cues for the directional migration of CXCR4-expressing human endothelial cells in response to CXCL12.

9.
Echocardiography ; 36(6): 1095-1102, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31038795

RESUMO

BACKGROUND: Stress testing in patients with low pretest probability (PTP) of coronary artery disease (CAD) has become an increasing practice, potentially leading to underestimation of its true clinical value. Our aim was to describe the current use of most employed imaging functional tests and their prognostic value. METHODS AND RESULTS: We selected patients with low PTP of CAD (CAD consortium clinical score < 15%) who underwent exercise or dipyridamole stress echocardiography or single photon emission computed tomography for suspected angina. Main exclusions were age < 45, known CAD, and abnormal rest wall motion. Of the 2279 subjects undergoing stress test, 883 (39%) had low PTP, and 91 (10.3%) had a positive test for ischemia. After a median follow-up of 5.8 years, 36 patients had events (21 died, 14 had nonfatal myocardial infarction). The percentage of events in the abnormal and normal stress test groups were similar (5 [5.5%] vs 31 [3.9%], P = ns), as the annualized event rate (0.87% vs 0.62%, P = ns). Age was the only variable associated with outcome in the regression analysis (hazard ratio 1.072, 95% CI 1.034-1.113, P < 0.001). An abnormal result was not associated with worse outcome in each of the subgroups of functional tests. CONCLUSIONS: In our geographical area, a considerable proportion of patients undergoing imaging functional tests for stable chest pain have a low estimated PTP of CAD. Of these, 1 in 10 resulted positive for inducible ischemia. However, none of the most common imaging functional tests, single photon emission computed tomography (SPECT), and stress echocardiography offer prognostic information in these patients.


Assuntos
Dor no Peito/diagnóstico por imagem , Dor no Peito/fisiopatologia , Doença da Artéria Coronariana , Ecocardiografia sob Estresse/métodos , Teste de Esforço/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos
10.
Eur Arch Otorhinolaryngol ; 276(6): 1829-1835, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30993468

RESUMO

PURPOSE: The aim of this study is to analyze the efficacy of a new modified pharyngoplasty technique with barbed sutures: barbed suspension pharyngoplasty (BSP). METHODS: We enrolled patients affected by obstructive sleep apnea-hypopnea syndrome (OSAHS), having the main site of obstruction at the palatal and lateral pharyngeal walls, who refused or failed to tolerate CPAP therapy and underwent non-resective pharyngoplasty with barbed sutures between January 2014 and October 2017. Two surgical techniques with barbed sutures were used: barbed reposition pharyngoplasty (BRP) and BSP; the main characteristics of the latter are a double passage of the needle, each side, through the soft palate. RESULTS: Forty-two patients met the study inclusion criteria and were included in the analysis. Twenty-two patients underwent BRP and 20 BSP. Patients treated with both BRP and BSP achieved significant improvement in polysomnographic parameters: AHI, ODI, t90%, and daily sleepiness tested by the ESS questionnaire (p < 0.001). There were no significant differences between groups considering gender, age, or severity of OSAHS (p > 0.05). Outcomes were also comparable (p = 0.10) in the two groups; patients who underwent BSP had successful treatment in 100% of cases, compared to 86% with BRP, with a cure rate of 40% vs. 18%. CONCLUSIONS: BSP is a novel surgical technique that is effective in treating oropharyngeal collapse and can be tailored for patients with high collapsibility of the soft palate who might benefit from the palatal stiffness given by multiple passages of the suture inside it.


Assuntos
Orofaringe/cirurgia , Faringe/cirurgia , Procedimentos Cirúrgicos Reconstrutivos , Apneia Obstrutiva do Sono/cirurgia , Técnicas de Sutura , Suturas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Otorrinolaringológicos , Palato Mole/cirurgia , Polissonografia , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
11.
J Craniofac Surg ; 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30817544

RESUMO

Rhinogenic headache (RH) is a widespread pain syndrome but its pathogenesis and treatment are still unclear. Some authors recognize a correlation between RH and mucosal contact points or some other sinonasal anatomical variations. The authors conducted a retrospective case-control study to analyze the correlation between radiological findings and clinical symptoms.One hundred-nineteen adults with Para-Nasal Sinuses Computed Tomography (PNS-CT) scans were included: 64 patients who have originally undergone PNS-CT scan as part of rhinogenic headache workup (Group A), and 55 controls in whom PNS-CT scans were obtained for other purposes (Group B). All subjects were asked to report their symptoms using a headache scoring system. PNS-CT scans of all subjects were analyzed for presence of mucosal contact points, middle turbinate concha bullosa (MTCB) and frontoethmoidal cells.The most common anatomical abnormality found in our series was MTCB, reported in 60.9% of patients in Group A and 41.8% of those in Group B. A statistically significant prevalence was found in Group A compared to Group B regarding the presence of MTCB (P = 0.037) and Type II (P = 0.016) and Type III (P = 0.039) frontoethmoidal cells. No statistically significant difference (P >0.05) was found between Group A and Group B regarding the presence of mucosal contact points at each site.Multiple anatomical variations in nasal and paranasal sinuses may cause a rhinogenic headache with different characteristics. Some of these, such as concha bullosa of middle turbinate or type II and III Kuhn cells, have shown a significant association with rhinogenic headache. No statistically significant association was found between presence of headache and mucosal contact points and type I and IV frontal cells. These findings can be very helpful for the surgeons that want to deal with the treatment of RH.

12.
Echocardiography ; 36(4): 639-650, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30834592

RESUMO

BACKGROUND: To assess prevalence and clinical implications of left ventricular (LV) remodeling considering: LV volume, mass and relative wall thickness at the time of aortic valve stenosis diagnosis. METHODS AND RESULTS: We retrospectively analyzed 343 patients (age 79.2 ± 9.5 years, 48.1% males) with functional aortic valve area (AVA) ≤ 1.5 cm2 . LV geometric patterns and clinical outcomes (combined death, cardiac hospitalization, aortic valve replacement [AVR]) were evaluated. According to the new LV remodeling classification, 4.9% had normal geometry, 7.5% concentric remodeling, 39.3% concentric hypertrophy (LVH), 22.4% mixed LVH, 12.5% dilated LVH, 3.2% eccentric LVH and 4.3% eccentric remodeling, 5.5% had not classifiable LVH. Indexed stroke volume (SVi) was higher in patients with concentric LVH (40.3 ± 11.9 mL/m2 ) and mixed LVH (41.6 ± 13.4 mL/m2 ) and lower in patients with eccentric LVH (24.9 ± 7.7 mL/m2 ), concentric (36.6 ± 12.7 mL/m2 ) and eccentric remodeling (34.9 ± 9.5 mL/m2 ), P = 0.003. During a median follow-up of 2.2 years, 260 (75.8%) had the combined end point. A significant association between the combined end point and LV dilation (P = 0.010) or LV remodeling patterns (P = 0.0001) was found. After multivariable adjustment for AVR, concentric remodeling (HR 3.12, IC 95% 1.14-8.55; P = 0.02) and dilated LVH (HR 3.48, IC 95% 1.31-9.27; P = 0.01) were strongly associated with death or cardiac hospitalizations. CONCLUSIONS: In patients with AVA ≤ 1.5 cm2 , when the new LV remodeling classification system is applied, only a minority had normal geometry and less than half had "classic" concentric LVH or remodeling. LV volume dilatation is frequent and associated with adverse outcome. Concentric remodeling, eccentric remodeling, dilated LVH had the worst noninvasive hemodynamic profile and prognosis.


Assuntos
Estenose da Valva Aórtica/fisiopatologia , Ventrículos do Coração/patologia , Remodelação Ventricular/fisiologia , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/patologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Tamanho do Órgão , Estudos Retrospectivos
13.
Chemistry ; 25(14): 3477-3482, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30632649

RESUMO

The discovery of stimuli-responsive high affinity host-guest pairs with potential applications under biologically relevant conditions is a challenging goal. This work reports a high-affinity 1:1 complex formed between cucurbit[8]uril and a water-soluble photochromic diarylethene derivative. It was found that, by confining the open isomer within the cavity of the receptor, a redshift in the absorption spectrum and an enhancement of the photocyclization quantum yield from Φ=0.04 to Φ=0.32 were induced. This improvement in the photochemical performance enables quantitative photocyclization with visible light that, together with the near-infrared light-induced ring-opening reaction and the 100-fold selectivity for the closed isomer, confirms this as an outstanding light-responsive affinity pair.

14.
J Am Coll Cardiol ; 73(3): 264-274, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30678755

RESUMO

BACKGROUND: Scientific guidelines consider atrial fibrillation (AF) complicating degenerative mitral regurgitation (DMR) a debated indication for surgery. OBJECTIVES: This study analyzed the prognostic/therapeutic implications of AF at DMR diagnosis and long-term. METHODS: Patients were enrolled in the MIDA (Mitral Regurgitation International Database) registry, which reported the consecutive, multicenter, international experience with DMR due to flail leaflets echocardiographically diagnosed. RESULTS: Among 2,425 patients (age 67 ± 13 years; 71% male, 67% asymptomatic, ejection fraction 64 ± 10%), 1,646 presented at diagnosis with sinus rhythm (SR), 317 with paroxysmal AD, and 462 with persistent AF. Underlying clinical/instrumental characteristics progressively worsened from SR to paroxysmal to persistent AF. During follow-up, paroxysmal and persistent AF were associated with excess mortality (10-year survival in SR and in paroxysmal and persistent AF was 74 ± 1%, 59 ± 3%, and 46 ± 2%, respectively; p < 0.0001), that persisted 20 years post-diagnosis and independently of all baseline characteristics (p values <0.0001). Surgery (n = 1,889, repair 88%) was associated with better survival versus medical management, regardless of all baseline characteristics and rhythm (adjusted hazard ratio: 0.26; 95% confidence interval: 0.23 to 0.30; p < 0.0001) but post-surgical outcome remained affected by AF (10-year post-surgical survival in SR and in paroxysmal and persistent AF was 82 ± 1%, 70 ± 4%, and 57 ± 3%, respectively; p < 0.0001). CONCLUSIONS: AF is a frequent occurrence at DMR diagnosis. Although AF is associated with older age and more severe presentation of DMR, it is independently associated with excess mortality long-term after diagnosis. Surgery is followed by improved survival in each cardiac rhythm subset, but persistence of excess risk is observed for each type of AF. Our study indicates that detection of AF, even paroxysmal, should trigger prompt consideration for surgery.


Assuntos
Fibrilação Atrial/complicações , Insuficiência da Valva Mitral/complicações , Sistema de Registros , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/mortalidade , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/mortalidade , Prevalência
15.
Echocardiography ; 36(1): 38-46, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30407661

RESUMO

BACKGROUND: Left ventricular (LV) remodeling due to aortic regurgitation (AR) often leads to maladaptive responses. We assessed the prevalence and clinical implications of LV remodeling considering LV volume, mass, and relative wall thickness at the time of AR diagnosis. METHODS AND RESULTS: Between 2008 and 2017, 370 consecutive patients (mean age 67.3 ± 16.1 years, 56.5% males), with moderate or severe AR, were retrospectively analyzed. LV geometric patterns and clinical outcomes (cardiovascular death, hospitalization for heart failure, or aortic valve replacement) were evaluated. LV dilatation (LV end-diastolic volume >75 mL/m2 ) was present in 228 patients (61.6%). Applying the new LV remodeling classification system, 40 (10.8%) patients had normal geometry, 14 (3.8%) concentric remodeling, 43 (11.6%) concentric hypertrophy (LVH), 45 (12.2%) indeterminate LVH, 38 (10.3%) mixed LVH, 93 (25.1%) dilated LVH, 54 (14.6%) eccentric LVH, and 43 (11.6%) eccentric remodeling. During a median follow-up of 3.48 years (25th-75th percentile 0.91-5.57), 97 (26.2%) had the combined endpoint. LV dilation (P < 0.001), LVH (P < 0.001), and LV remodeling patterns were significantly associated with the combined endpoint. After multivariable adjustment for age, EF, aortic stenosis, CAD history, and moderate mitral regurgitation, dilated LVH (HR 7.61, IC 95% 1.82-31.80; P = 0.005) and eccentric LVH (HR 7.91, IC 95% 1.82-34.38; P = 0.006) were associated with adverse outcome compared to eccentric remodeling, that showed the best event-free survival rate. CONCLUSIONS: In a contemporary cohort of patients with AR, applying the new LV remodeling classification system, only a minority had normal geometry. Dilated LVH and eccentric LVH showed distinct outcome penalty after adjustment for confounders.


Assuntos
Insuficiência da Valva Aórtica/patologia , Ecocardiografia/métodos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Avaliação de Resultados da Assistência ao Paciente , Idoso , Insuficiência da Valva Aórtica/complicações , Doença Crônica , Feminino , Insuficiência Cardíaca/complicações , Humanos , Masculino , Tamanho do Órgão , Prevalência , Estudos Retrospectivos , Análise de Sobrevida , Remodelação Ventricular
16.
Cardiovasc Ultrasound ; 16(1): 20, 2018 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-30249305

RESUMO

BACKGROUND: The effectiveness trial "Stress echo (SE) 2020" evaluates novel applications of SE in and beyond coronary artery disease. The core protocol also includes 4-site simplified scan of B-lines by lung ultrasound, useful to assess pulmonary congestion. PURPOSE: To provide web-based upstream quality control and harmonization of B-lines reading criteria. METHODS: 60 readers (all previously accredited for regional wall motion, 53 B-lines naive) from 52 centers of 16 countries of SE 2020 network read a set of 20 lung ultrasound video-clips selected by the Pisa lab serving as reference standard, after taking an obligatory web-based learning 2-h module ( http://se2020.altervista.org ). Each test clip was scored for B-lines from 0 (black lung, A-lines, no B-lines) to 10 (white lung, coalescing B-lines). The diagnostic gold standard was the concordant assessment of two experienced readers of the Pisa lab. The answer of the reader was considered correct if concordant with reference standard reading ±1 (for instance, reference standard reading of 5 B-lines; correct answer 4, 5, or 6). The a priori determined pass threshold was 18/20 (≥ 90%) with R value (intra-class correlation coefficient) between reference standard and recruiting center) > 0.90. Inter-observer agreement was assessed with intra-class correlation coefficient statistics. RESULTS: All 60 readers were successfully accredited: 26 (43%) on first, 24 (40%) on second, and 10 (17%) on third attempt. The average diagnostic accuracy of the 60 accredited readers was 95%, with R value of 0.95 compared to reference standard reading. The 53 B-lines naive scored similarly to the 7 B-lines expert on first attempt (90 versus 95%, p = NS). Compared to the step-1 of quality control for regional wall motion abnormalities, the mean reading time per attempt was shorter (17 ± 3 vs 29 ± 12 min, p < .01), the first attempt success rate was higher (43 vs 28%, p < 0.01), and the drop-out of readers smaller (0 vs 28%, p < .01). CONCLUSIONS: Web-based learning is highly effective for teaching and harmonizing B-lines reading. Echocardiographers without previous experience with B-lines learn quickly.


Assuntos
Ecocardiografia sob Estresse/normas , Pulmão/diagnóstico por imagem , Edema Pulmonar/diagnóstico , Controle de Qualidade , Feminino , Humanos , Internet , Masculino , Pessoa de Meia-Idade
17.
Genes Chromosomes Cancer ; 57(12): 645-652, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30136351

RESUMO

Foci of papillary or follicular thyroid carcinoma are frequently noted in thyroidectomy specimens of anaplastic thyroid carcinoma (ATC). However, whether ATCs evolve from these co-existing well-differentiated thyroid carcinomas (WDTCs) has not been well-understood. To investigate the progression of ATC in patients with co-existing WDTCs, five ATC tumors with co-existing WDTCs and matching normal tissues were whole-exome sequenced. After mapping the somatic alteration landscape, evolutionary lineages were constructed by sub-clone analysis. Though each tumor harbored at least some unique private mutations, all five ATCs demonstrated numerous overlapping mutations with matched WDTCs. Clonal analysis further demonstrated that each ATC/WDTC pair shared a common ancestor, with some pairs diverging early in their evolution and others in which the ATC seems to arise directly from a sub-clone of the WDTC. Though the precise lineal relationship remains ambiguous, based on the genetic relationship, our study clearly suggests a shared origin of ATC and WDTC.


Assuntos
Evolução Clonal , Carcinoma Anaplásico da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinogênese , Diferenciação Celular , Estudos de Coortes , Análise Mutacional de DNA , DNA de Neoplasias , Exoma , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia
18.
Transpl Infect Dis ; 20(5): e12966, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30014622

RESUMO

Kaposi sarcoma (KS) may rarely occur in transplant recipients through primary human herpesvirus-8 (HHV-8) infection from a seropositive donor. This report describes a patient who developed hepatic KS after receiving a split liver transplant from an HHV-8-positive donor. The recipient was treated with liposomal doxorubicin after reduction in immunosuppression led to acute cellular rejection. This treatment achieved regression of KS while preserving allograft function, demonstrating a successful therapeutic strategy for this malignancy.


Assuntos
Doxorrubicina/análogos & derivados , Infecções por Herpesviridae/transmissão , Neoplasias Hepáticas/tratamento farmacológico , Transplante de Fígado/efeitos adversos , Sarcoma de Kaposi/tratamento farmacológico , Aloenxertos/diagnóstico por imagem , Aloenxertos/patologia , Aloenxertos/virologia , Doxorrubicina/uso terapêutico , Feminino , Infecções por Herpesviridae/diagnóstico , Infecções por Herpesviridae/patologia , Infecções por Herpesviridae/virologia , Herpesvirus Humano 8/isolamento & purificação , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/virologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Sarcoma de Kaposi/diagnóstico , Sarcoma de Kaposi/patologia , Sarcoma de Kaposi/virologia , Doadores de Tecidos , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Adulto Jovem
19.
Am J Clin Pathol ; 150(4): 353-363, 2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-30020407

RESUMO

Objectives: Intraoperative pathology consultation (IOC) to assess margins is frequently requested during surgery of the stomach and gastroesophageal junction. Methods: We studied 110 consecutive patients undergoing gastrectomy with IOC margin assessment. Results: Gastric margins at IOC utilized the most blocks but were least often positive. In 64% of patients, the entire gastric margin was examined using average six blocks; representative sections were examined in 25% of patients using two blocks. There was no difference in patient outcome between those who had entire vs representative sections of margin examined. Gross variables showing strongest associations with positive margins were tumor size and tumor distance to margin. Tumors sized greater than 2.3 cm had significantly increased risk of positive margin, and tumor distance greater than 4.5 cm to margin was associated with negative margins. Conclusions: We conclude representative sections of the closest gastric margin are sufficient to ensure R0 resection in the majority of cases.


Assuntos
Adenocarcinoma/patologia , Carcinoma de Células Escamosas/patologia , Gastrectomia , Tumores do Estroma Gastrointestinal/patologia , Cuidados Intraoperatórios , Margens de Excisão , Neoplasias Gástricas/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/cirurgia , Feminino , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia
20.
J Clin Endocrinol Metab ; 103(7): 2640-2650, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29726952

RESUMO

Context: Follicular thyroid carcinoma (FTC) is classified into minimally invasive (miFTC), encapsulated angioinvasive (eaFTC), and widely invasive (wiFTC) subtypes, according to the 2017 World Health Organization guidelines. The genetic signatures of these subtypes may be crucial for diagnosis, prognosis, and treatment but have not been described. Objective: Identify and describe the genetic underpinnings of subtypes of FTC. Methods: Thirty-nine tumors, comprising 12 miFTCs, 17 eaFTCs, and 10 wiFTCs, were whole-exome sequenced and analyzed. Somatic mutations, constitutional sequence variants, somatic copy number alterations, and mutational signatures were described. Clinicopathologic parameters and mutational profiles were assessed for associations with patient outcomes. Results: Total mutation burden was consistent across FTC subtypes, with a median of 10 (range 1 to 44) nonsynonymous somatic mutations per tumor. Overall, 20.5% of specimens had a mutation in the RAS subfamily (HRAS, KRAS, or NRAS), with no notable difference between subtypes. Mutations in TSHR, DICER1, EIF1AX, KDM5C, NF1, PTEN, and TP53 were also noted to be recurrent across the cohort. Clonality analysis demonstrated more subclones in wiFTC. Survival analysis demonstrated worse disease-specific survival in the eaFTC and wiFTC cohorts, with no recurrences or deaths for patients with miFTC. Mutation burden was associated with worse prognosis, independent of histopathological classification. Conclusions: Though the number and variety of somatic variants are similar in the different histopathological subtypes of FTC in our study, mutational burden was an independent predictor of mortality and recurrence.


Assuntos
Adenocarcinoma Folicular/genética , Mutação , Neoplasias da Glândula Tireoide/genética , Adenocarcinoma Folicular/mortalidade , Adenocarcinoma Folicular/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Variações do Número de Cópias de DNA , Feminino , Genes ras/genética , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Prognóstico , Recidiva , Análise de Sobrevida , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Adulto Jovem
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