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1.
J Neurooncol ; 141(2): 347-354, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30414096

RESUMO

PURPOSE: Clinical factors and neuro-imaging in patients with glioblastoma who appear to progress following standard chemoradiation are unable to reliably distinguish tumor progression from pseudo-progression. As a result, surgery is commonly recommended to establish a final diagnosis. However, studies evaluating the pathologists' agreement on pathologic diagnoses in this setting have not been previously evaluated. METHODS: A hypothetical clinical history coupled with images of histological sections from 13 patients with glioblastoma who underwent diagnostic surgery for suspected early recurrence were sent to 101 pathologists from 50 NCI-designated Cancer Centers. Pathologists were asked to provide a final diagnosis (active tumor, treatment effect, or unable to classify) and to report on percent active tumor, treatment effect, and degree of cellularity and degree of mitotic activity. RESULTS: Forty-eight pathologists (48%) from 30 centers responded. In three cases > 75% of pathologists diagnosed active tumor. In two cases > 75% diagnosed treatment effect. However, in the remaining eight cases the disparity in diagnoses was striking (maximum agreement on final diagnosis ranged from 36 to 68%). Overall, only marginal agreement was observed in the overall assessment of disease status [kappa score 0.228 (95% CI 0.22-0.24)]. CONCLUSIONS: Confidence in any clinical diagnostic assay requires that very similar results are obtained from identical specimens evaluated by sophisticated clinicians and institutions. The findings of this study illustrate that the diagnostic agreement between different cases of repeat resection for suspected recurrent glioblastoma can be variable. This raises concerns as pathological diagnoses are critical in directing standard and experimental care in this setting.


Assuntos
Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Encefálicas/cirurgia , Diagnóstico Diferencial , Progressão da Doença , Glioblastoma/cirurgia , Humanos , Recidiva Local de Neoplasia/cirurgia , Variações Dependentes do Observador
2.
Histopathology ; 73(2): 220-229, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29667709

RESUMO

AIMS: Gastric heterotopia (GH) has been described throughout the gastrointestinal tract. However, the colorectal region is an extremely rare location for it. We describe the clinicopathological features of GH of the colon, rectum and anus. METHODS AND RESULTS: We identified 33 cases in 20 males and 13 females (median age = 54 years; range = 4 months-73 years). Sites included the rectum (n = 26), anus (n = 4), ileocaecal junction (n = 1), ascending colon (n = 1) and descending colon (n = 1). Presenting symptoms (n = 27) included haematochezia (41%) and altered bowel habits (4%); 15 patients (55%) were asymptomatic. On colonoscopy (n = 31), all appeared as solitary lesions (median size = 6.5 mm, range = 2-55 mm), either as polyps (61%), raised erythematous patches (23%), an ulcer (10%), within a rectal diverticulum (3%) or a haemorrhoid (3%). Patients were managed by polypectomy. One with an associated carcinoma in the area of GH underwent resection. No morbidity related to GH itself was reported following excision. Histologically, heterotopic gastric mucosa was oxyntic (85%), mixed oxyntic and non-oxyntic (12%) and not specified (3%) types. In five patients a pyloric gland adenoma (PGA) arose from heterotopic gastric mucosa, two of which contained a focus of invasive adenocarcinoma. One case had associated surface foveolar-type low-grade dysplasia. Another had associated adenocarcinoma arising from the heterotopic mucosa. One example harboured Helicobacter pylori organisms. CONCLUSIONS: We highlight the features of GH in the distal GIT - the 'outlet patch'. Association with PGA, surface dysplasia and adenocarcinoma suggests that lower tract GH can undergo neoplastic transformation.


Assuntos
Canal Anal/patologia , Coristoma/patologia , Doenças do Colo/patologia , Doenças Retais/patologia , Estômago , Adolescente , Adulto , Idoso , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade
3.
J Vis Commun Med ; 38(3-4): 220-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26828553

RESUMO

Caretakers, researchers and photographers working in a busy academic settings, every day are faced with images that are awe-inspiring for their beauty and for the terror they may represent to patients suffering from disease. Beauty in this context is a relative term. It may be seen as the delicate lacework of cells within the normal human brain reminiscent of a Jackson Pollack masterpiece, or the multitude of colors and textures formed by fungal organisms in a microbiology lab. Herein lies the juxtaposition image makers seek to represent. When contemplated in isolation, each represents a visually interesting image. However, when viewed with an awareness of the context in which the image was obtained, each image takes on the ability to evoke an alternative human emotion.


Assuntos
Arte , Diagnóstico por Imagem , Humanos
4.
Am J Surg Pathol ; 46(9): 1180-1195, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35796652

RESUMO

Complete hydatidiform moles (CHMs) and partial hydatidiform moles (PHMs) are abnormal gestations characterized by vesicular chorionic villi accompanied by variable trophoblastic hyperplasia, with or without embryonic development. CHMs are purely androgenetic (only paternal [P] chromosome complements), mostly homozygous/monospermic (~85%) but occasionally heterozygous/dispermic, whereas PHMs are overwhelmingly diandric triploid (2 paternal [P] and 1 maternal [M] chromosome complements) and heterozygous/dispermic (>95%). The presence of a fetus in a molar pregnancy usually indicates a PHM rather than a CHM; however, CHMs and PHMs rarely can be associated with a viable fetus or a nonmolar abortus in twin pregnancies and rare multiple gestation molar pregnancies have been reported. A "one-oocyte-model," with diploidization of dispermic triploid zygotes, has been proposed for twin CHM with coexisting fetus, and a "two-oocyte-model" has been proposed for twin PHM with coexisting fetus. Among 2447 products of conception specimens, we identified 21 cases of twin/multiple gestations with a molar component, including 20 CHMs (17 twins, 2 triplets, 1 quintuplet) and 1 PHM (twin). P57 immunohistochemistry was performed on all; DNA genotyping of molar and nonmolar components was performed on 9 twin CHMs, 1 triplet CHM, 1 quintuplet CHM, and 1 twin PHM. All CHM components were p57-negative and those genotyped were purely androgenetic. Twin CHMs had genotypes of P1M1+P2P2 in 5, P1M1+P1P1 in 1, and P1M1+P2P3 in 1, consistent with involvement of 1 oocyte and from 1 to 3 sperm-most commonly a homozygous CHM but involving 2 sperm in the whole conception-and compatible with a "one-oocyte-model." The triplet CHM was P1M1+P1P1+P2M2 and the quintuplet CHM was P1M1+P2M2+P2M2+P3M3+P4P4, consistent with involvement of 2 sperm and at least 2 oocytes for the triplet and 4 sperm and at least 3 oocytes for the quintuplet. The twin PHM had a P1M1+P2P3M2 genotype, consistent with involvement of 2 oocytes and 3 sperm. p57 immunohistochemistry is highly reliable for diagnosis of CHMs in twin/multiple gestations. Refined diagnosis of molar twin/multiple gestations is best accomplished by correlating morphology, p57 immunohistochemistry, and molecular genotyping, with the latter clarifying zygosity/parental chromosome complement contributions to these conceptions.


Assuntos
Mola Hidatiforme , Neoplasias Uterinas , Inibidor de Quinase Dependente de Ciclina p57/genética , Feminino , Genótipo , Humanos , Mola Hidatiforme/diagnóstico , Masculino , Pais , Gravidez , Sêmen , Triploidia , Neoplasias Uterinas/patologia
5.
Exp Neurol ; 323: 113073, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31639375

RESUMO

During mammalian embryonic development sensory and motor axons interact as an integral part of the pathfinding process. During regeneration, however, little is known of their interactions with one another. It is thus possible that sensory axons might influence motor axon regeneration in ways not currently appreciated. To explore this possibility we have developed an organotypic model of post-natal nerve regeneration in which sensory and motor axons are color-coded by modality. Motor axons that express yellow fluorescent protein (YFP) and sensory axons that express red fluorescent protein (RFP) are blended within a three-dimensional segment of peripheral nerve. This nerve is then transected, allowing axons to interact with one another as they grow out on a collagen/laminin gel that is initially devoid of directional cues. Within hours it is apparent that sensory axons extend more rapidly than motor axons and precede them during the early stages of regeneration, the opposite of their developmental order. Motor axons thus enter an environment already populated with sensory axons, and they adhere to these axons throughout most of their course. As a result, motor axon growth is reduced dramatically. Physical delay of sensory regeneration, allowing motor axons to grow ahead, restores normal motor growth; direct axonal interactions on the gel, rather than some other aspect of the model, are thus responsible for motor inhibition. Potential mechanisms for this inhibition are explored by electroporating siRNA to the neural cell adhesion molecule (NCAM) and the L1 adhesion molecule (L1CAM) into dorsal root ganglia (DRGs) to block expression of these molecules by regenerating sensory axons. Although neither maneuver improved motor regeneration, the results were consistent with early receptor-mediated signaling among axons rather than physical adhesion as the mechanism of motor inhibition in this model.


Assuntos
Axônios/fisiologia , Neurônios Motores/fisiologia , Regeneração Nervosa/fisiologia , Células Receptoras Sensoriais/fisiologia , Animais , Técnicas de Cocultura/métodos , Gânglios Espinais/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Moléculas de Adesão de Célula Nervosa/metabolismo , Técnicas de Cultura de Órgãos/métodos , Nervos Periféricos/fisiologia , Medula Espinal/fisiologia
6.
J Mol Cell Cardiol ; 47(5): 576-85, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19766235

RESUMO

Stimulation of the beta-adrenergic system is important in the pathological response to sustained cardiac stress, forming the rationale for the use of beta-blockers in heart failure. The beta3-adrenoreceptor (AR) is thought to couple to the inhibitory G-protein, G(i), with downstream signaling through nitric oxide, although its role in the heart remains controversial. In this study, we tested whether lack of beta3-AR influences the myocardial response to pressure-overload. Baseline echocardiography in mice lacking beta3-AR (beta3(-/-)) compared to wild type (WT) showed mild LV hypertrophy at 8 weeks that worsened as they aged. beta3(-/-) mice had much greater mortality after transverse aortic constriction (TAC) than WT controls. By 3 weeks of TAC, systolic function was worse. After 9 weeks of TAC, beta3(-/-) mice also had greater LV dilation, myocyte hypertrophy and enhanced fibrosis. NOS activity declined in beta3(-/-)TAC hearts after 9 weeks, and total and NOS-dependent superoxide rose, indicating heightened oxidative stress and NOS uncoupling. The level of eNOS phosphorylation in beta3(-/-)TAC hearts was diminished, and nNOS and iNOS expression levels were increased. GTP cyclohydrolase-1 expression was reduced, although total BH4 levels were not depleted. 3 weeks of BH4 treatment rescued beta3(-/-) mice from worsened remodeling after TAC, and lowered NOS-dependent superoxide. Thus, lack of beta3-AR signaling exacerbates cardiac pressure-overload induced remodeling and enhances NOS uncoupling and consequent oxidant stress, all of which can be rescued with exogenous BH4. These data suggest a cardioprotective role for the beta3-AR in modulating oxidative stress and adverse remodeling in the failing heart.


Assuntos
Hipertrofia Ventricular Esquerda/genética , Hipertrofia Ventricular Esquerda/patologia , Receptores Adrenérgicos beta 3/fisiologia , Remodelação Ventricular/genética , Remodelação Ventricular/fisiologia , Fatores Etários , Animais , Biopterinas/análogos & derivados , Biopterinas/uso terapêutico , Western Blotting , Cardiomiopatias/genética , Cardiomiopatias/patologia , Ecocardiografia , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Masculino , Camundongos , Camundongos Mutantes , Óxido Nítrico Sintase/metabolismo , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , Receptores Adrenérgicos beta 3/genética , Superóxidos/metabolismo , Vasoconstrição/fisiologia , Remodelação Ventricular/efeitos dos fármacos
7.
Int J Surg Pathol ; 27(1): 15-18, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29944023

RESUMO

INTRODUCTION: Colon biopsies are among the most frequently examined specimens by pathologists. Many pathology practices, ours included, review upfront levels on all gastrointestinal biopsies. In our experience, when a lesion is present on specimens labeled "colon polyp," it is readily identified on the first level. To test our hypothesis, we re-reviewed 500 cases in which a lesion was identified histologically and determined if the diagnosis could be made on the first level. Furthermore, we examined 50 additional cases of high-grade dysplasia/carcinoma to determine if the higher-grade component was also present on the first level. MATERIALS AND METHODS: Cases were retrieved for lesions that could account for a colon polyp clinically, and the first level was examined to determine if lesional tissue was present on the first level. Fifty additional cases of higher-grade lesions were included to ensure higher-grade lesions were present on the first level. RESULTS: Overall, 497/500 (99.4%) of the non-high-grade lesions were present on the first level, whereas 3/500 (0.6%) required the additional level for diagnosis. All 50 high-grade lesions were present on the first level examined. DISCUSSION: Many pathology practices routinely order upfront levels on all gastrointestinal biopsies, often generating 2 or 3 slides. Additional slides increase costs, increase the likelihood of laboratory-generated errors, and can waste limited tissue on small biopsies for which ancillary studies may be necessary. Our study showed that a single level is sufficient in the overwhelming majority of cases in which a lesion is identified histologically.


Assuntos
Pólipos do Colo/diagnóstico , Pólipos do Colo/patologia , Patologia Clínica/métodos , Humanos
8.
J Biocommun ; 42(1): e1, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-36406759

RESUMO

Despite the fame of Roman Vishniac's photography of Jewish communities in pre-Holocaust Europe; what is relatively unknown today to the photography or science communities - despite the recognition it received at the time of its creation - is that Vishniac's major efforts in photography were neither documentary nor artistic. Rather, the vast majority of his lifetime of photographic work focused on the biological world. Reviewed here is the phenomenal scope and quantity of biological photography and cinematography produced by Roman Vishniac over a five-decade period. From zoo animals to the tiniest of microorganisms, from time-lapse studies of vascular physiology to widely distributed biology classroom films, from spreads in LIFE magazine to advertisements for an insect sting analgesic; Vishniac's ability to capture and create images - almost exclusively of living subjects - was sought after by scientific researchers, popular magazines, movie producers, news organizations and commercial entities. Vishniac's body of scientific photography, both still and ciné, often produced by him from initial concept through writing and shooting - in an age before the technological advances in imaging that we all now enjoy - and despite its later eclipse by his own earlier images, was regarded as the finest and most imaginative of its time.

9.
Cardiovasc Pathol ; 24(5): 322-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26141114

RESUMO

We present the cardiac findings from the autopsy of a 28-year-old male with mucopolysaccharidosis VII (MPS VII), also known as Sly Syndrome, whose diagnosis was confirmed by biochemical testing. The patient died a sudden cardiac death. Autopsy showed thickened and stenotic aortic valve leaflets as well as marked concentric intimal thickening of the aorta and muscular arteries. There was left ventricular hypertrophy as well as mild papillary muscle thickening and fusion. Increased colloid iron staining was seen in the small- and medium-sized arteries of the heart and at the intercalated discs. We discuss the patient's premortem echocardiographic and electrocardiographic studies. In addition, we discuss the pathogenesis of MPS VII and review previous literature on its anatomic and pathologic features.


Assuntos
Aorta/patologia , Valvas Cardíacas/patologia , Mucopolissacaridose VII/patologia , Miocárdio/patologia , Adulto , Autopsia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/patologia , Humanos , Masculino , Mucopolissacaridose VII/complicações
10.
Nat Med ; 21(9): 1060-4, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26259033

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed after the disease has metastasized; it is among the most lethal forms of cancer. We recently described aberrant expression of an open reading frame 1 protein, ORF1p, encoded by long interspersed element-1 (LINE-1; L1) retrotransposon, in PDAC. To test whether LINE-1 expression leads to somatic insertions of this mobile DNA, we used a targeted method to sequence LINE-1 insertion sites in matched PDAC and normal samples. We found evidence of 465 somatic LINE-1 insertions in 20 PDAC genomes, which were absent from corresponding normal samples. In cases in which matched normal tissue, primary PDAC and metastatic disease sites were available, insertions were found in primary and metastatic tissues in differing proportions. Two adenocarcinomas secondarily involving the pancreas, but originating in the stomach and duodenum, acquired insertions with a similar discordance between primary and metastatic sites. Together, our findings show that LINE-1 contributes to the genetic evolution of PDAC and suggest that somatic insertions are acquired discontinuously in gastrointestinal neoplasms.


Assuntos
Carcinoma Ductal Pancreático/genética , Evolução Clonal , Elementos Nucleotídeos Longos e Dispersos/fisiologia , Neoplasias Pancreáticas/genética , Fator Apoptótico 1 Ativador de Proteases/análise , Humanos
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