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1.
Int J Surg Pathol ; 28(1): 92-98, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31409181

RESUMO

Primary rhabdomyosarcoma of the adult prostate is rare and associated with an aggressive clinical course. Given the limited number of cases reported about the prostate, little is known about the impact of molecular mutations on tumor biology and prognosis in adults. In this article, we present a case of primary embryonal rhabdomyosarcoma of the adult prostate with a complete molecular mutational profile of the tumor.

2.
Acta Cytol ; 64(1-2): 63-70, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30889579

RESUMO

The association between high-risk genotypes of human papillomavirus (hr-HPV) and cervical cancer is well established. As hr-HPV testing is rapidly becoming a part of routine cervical cancer screening, either in conjunction with cytology or as primary testing, the management of hr-HPV-positive women has to be tailored in a way that increases the detection of cervical abnormalities while decreasing unnecessary colposcopic biopsies or other invasive procedures. In this review, we discuss the overall utility and strategies of hr-HPV testing, as well as the advantages and limitations of potential triage strategies for hr-HPV-positive women, including HPV genotyping, p16/Ki-67 dual staining, and methylation assays.


Assuntos
Citodiagnóstico/métodos , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Detecção Precoce de Câncer/métodos , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Papillomaviridae/fisiologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Triagem , Neoplasias do Colo do Útero/complicações
3.
Am J Surg Pathol ; 43(7): 885-897, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31021855

RESUMO

Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy, but categorization is complicated by variability in grading systems and uncertain prognostic significance of MAML2 rearrangement. The aims of this study were to determine the prognostic significance of MEC grading systems and MAML2 rearrangement status. Fifty-three carcinomas originally diagnosed as MEC (45 primary; 8 recurrent) of major and minor salivary glands were graded according to modified Healey, Brandwein, AFIP, and Katabi systems. Fluorescence in situ hybridization for MAML2 rearrangement was performed. Clinical features and outcomes were recorded. Twenty-five (47%) carcinomas scored the same in all grading systems. The most common histologic feature leading to a diagnosis of intermediate grade was isolated solid growth. Brandwein assigned the highest percentage of high grade (29%) and AFIP the highest percentage of low grade (80%). MAML2 was rearranged in 37/46 (80%) cases. Forty-three (81%) were morphologically compatible with MEC, and these were more likely to be low-intermediate grade and MAML2-rearranged. Of primary carcinomas, 6 (13%) recurred. Statistically significant univariate risk factors for recurrence included non-MEC morphology, stage T4, and high Brandwein grade. Margin status, MAML2 rearrangement, and isolated solid growth were not predictive of recurrence. A binary grading system (Brandwein high vs. low-plus-intermediate) could be considered to better reflect biological behavior in MEC. Our study confirms that MAML2 wildtype tumors more likely represent high grade non-MECs, and prior studies demonstrating worse prognosis in MAML2-nonrearranged MECs may be diluted by high-grade non-MECs.

4.
Gynecol Oncol Rep ; 25: 94-97, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30014022

RESUMO

•Embryonal rhabdomyosarcoma of the uterine cervix and ovarian Sertoli-Leydig cell tumors are associated with DICER1 mutation•DICER1-associated tumors should prompt genetic counseling and testing•Somatic and germline genetic mutation profiles can be used to differentiate second primary from recurrent tumors.

5.
Am J Surg Pathol ; 42(6): 836-839, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29543676

RESUMO

Phyllodes tumor of the prostate is a rare mesenchymal tumor conventionally regarded as a stromal tumor of undetermined malignant potential. While the initial presentation is that of urinary obstruction and/or hematuria, the subsequent clinical behavior is thought to be a function of stromal cellularity and cytologic changes of malignancy. Of histologic interest, the epithelial component of this tumor varies, including intestinal metaplasia, as seen in the present case.


Assuntos
Células Epiteliais/patologia , Tumor Filoide/patologia , Neoplasias da Próstata/patologia , Idoso , Biópsia , Células Epiteliais/química , Fator de Transcrição GATA3/análise , Humanos , Imuno-Histoquímica , Calicreínas/análise , Masculino , Metaplasia , Gradação de Tumores , Tumor Filoide/química , Tumor Filoide/cirurgia , Antígeno Prostático Específico/análise , Neoplasias da Próstata/química , Neoplasias da Próstata/cirurgia
6.
J Surg Res ; 184(2): 730-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23290531

RESUMO

BACKGROUND: There is a growing recognition of the significance of host-pathogen interactions (HPIs) in gut biology leading to a reassessment of the role of bacteria in intestinal anastomotic leak. Understanding the complexities of the early postsurgical gut HPI requires integrating knowledge of both epithelial and bacterial behaviors to generate hypotheses of potential mechanisms of interaction. Agent-based modeling is a computational method well suited to achieve this goal, and we use an agent-based model (ABM) to examine alterations in the HPI affecting reestablishment of the epithelial barrier that may subsequently lead to anastomotic leak. METHODS: Computational agents representing Pseudomonas aeruginosa were added to a previously validated ABM of epithelial restitution. Simulated experiments were performed examining the effect of radiation on bacterial binding to epithelial cells, plausibility of putative binding targets, and potential mechanisms of epithelial cell killing by virulent bacteria. RESULTS: Simulation experiments incorporating radiation effects on epithelial monolayers produced binding patterns akin to those seen in vitro and suggested that promotility integrin-laminin associations represent potential sites for bacterial binding and disruption of restitution. Simulations of potential mechanisms of epithelial cell killing suggested that an injected cytotoxin was the means by which virulent bacteria produced the tissue destruction needed to generate an anastomotic leak, a mechanism subsequently confirmed with genotyping of the virulent P aeruginosa strain. CONCLUSIONS: This study emphasizes the utility of ABM as an adjunct to traditional research methods and provides insights into the potentially critical role of HPI in the pathogenesis of anastomotic leak.


Assuntos
Anastomose Cirúrgica , Fístula Anastomótica/fisiopatologia , Simulação por Computador , Interações Hospedeiro-Patógeno/fisiologia , Mucosa Intestinal/microbiologia , Modelos Biológicos , Pseudomonas aeruginosa/fisiologia , Animais , Aderência Bacteriana/fisiologia , Translocação Bacteriana/fisiologia , Permeabilidade da Membrana Celular/fisiologia , Células Cultivadas , Modelos Animais de Doenças , Células Epiteliais/microbiologia , Células Epiteliais/patologia , Técnicas In Vitro , Mucosa Intestinal/patologia , Fenótipo , Infecções por Pseudomonas/fisiopatologia , Ratos
7.
PLoS One ; 7(8): e44326, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22952955

RESUMO

The most feared complication following intestinal resection is anastomotic leakage. In high risk areas (esophagus/rectum) where neoadjuvant chemoradiation is used, the incidence of anastomotic leaks remains unacceptably high (≈ 10%) even when performed by specialist surgeons in high volume centers. The aims of this study were to test the hypothesis that anastomotic leakage develops when pathogens colonizing anastomotic sites become in vivo transformed to express a tissue destroying phenotype. We developed a novel model of anastomotic leak in which rats were exposed to pre-operative radiation as in cancer surgery, underwent distal colon resection and then were intestinally inoculated with Pseudomonas aeruginosa, a common colonizer of the radiated intestine. Results demonstrated that intestinal tissues exposed to preoperative radiation developed a significant incidence of anastomotic leak (>60%; p<0.01) when colonized by P. aeruginosa compared to radiated tissues alone (0%). Phenotype analysis comparing the original inoculating strain (MPAO1- termed P1) and the strain retrieved from leaking anastomotic tissues (termed P2) demonstrated that P2 was altered in pyocyanin production and displayed enhanced collagenase activity, high swarming motility, and a destructive phenotype against cultured intestinal epithelial cells (i.e. apoptosis, barrier function, cytolysis). Comparative genotype analysis between P1 and P2 revealed a single nucleotide polymorphism (SNP) mutation in the mexT gene that led to a stop codon resulting in a non-functional truncated protein. Replacement of the mutated mexT gene in P2 with mexT from the original parental strain P1 led to reversion of P2 to the P1 phenotype. No spontaneous transformation was detected during 20 passages in TSB media. Use of a novel virulence suppressing compound PEG/Pi prevented P. aeruginosa transformation to the tissue destructive phenotype and prevented anastomotic leak in rats. This work demonstrates that in vivo transformation of microbial pathogens to a tissue destroying phenotype may have important implications in the pathogenesis of anastomotic leak.


Assuntos
Fístula Anastomótica/microbiologia , Intestinos/microbiologia , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/patogenicidade , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/patologia , Animais , Apoptose/efeitos dos fármacos , Sequência de Bases , Caenorhabditis elegans , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Intestinos/efeitos dos fármacos , Intestinos/patologia , Intestinos/ultraestrutura , Masculino , Dados de Sequência Molecular , Fenótipo , Fosfatos/farmacologia , Polietilenoglicóis/farmacologia , Substâncias Protetoras/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Radiação , Ratos , Ratos Wistar , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Cicatrização/efeitos dos fármacos , Proteína da Zônula de Oclusão-1/metabolismo
8.
Surg Infect (Larchmt) ; 11(3): 299-305, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20583866

RESUMO

BACKGROUND: Clostridium difficile is the most common cause of nosocomial diarrhea in adults. Over the last decade, there has been a substantial increase in the disease-associated morbidity and mortality rate from this infection accompanied by identification of new hypervirulent strains. Fulminant colitis, a severe and complicated form of the disease that frequently necessitates surgical intervention, occurs in 3-8% of patients infected with C. difficile. The postoperative mortality rate for fulminant colitis continues to be dire, ranging from 34-57%. METHODS: Review of the literature to offer insight into the dilemma associated with the surgical management of fulminant C. difficile colitis and provide alternatives to total abdominal colectomy for treatment. RESULTS: Several recent studies have elucidated factors that contribute to the unacceptably high postoperative mortality rate: Surgical intervention too late in the course of the disease, lack of clearly defined guidelines for patient selection, and difficulty in predicting the clinical course of the disease. Perforation, need for vasopressor support, and end-organ damage all affect the postoperative mortality rate negatively. CONCLUSION: A high clinical suspicion and careful patient selection for colectomy is imperative to improve postoperative survival. An alternative surgical strategy for fulminant C. difficile colitis is laparoscopic creation of an ileostomy with total colonic washout.


Assuntos
Clostridium difficile/isolamento & purificação , Colectomia/efeitos adversos , Infecção Hospitalar/mortalidade , Infecção Hospitalar/terapia , Enterocolite Pseudomembranosa/mortalidade , Enterocolite Pseudomembranosa/terapia , Adulto , Infecção Hospitalar/microbiologia , Infecção Hospitalar/cirurgia , Enterocolite Pseudomembranosa/microbiologia , Enterocolite Pseudomembranosa/cirurgia , Humanos
9.
Dev Neurosci ; 32(1): 81-90, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20389079

RESUMO

We determined if heme oxygenase-2 (HO-2), an enzyme that degrades the pro-oxidant heme, confers neuroprotection in the developing brain after traumatic brain injury (TBI). Male HO-2 wild-type (WT) and homozygous knockout (KO) mice at postnatal day 21 were subjected to TBI and euthanized 1, 7, and 14 days later. Relative cerebral blood flow, measured by laser Doppler, cortical and hippocampal pathogenesis, and motor recovery were evaluated at all time points. Cerebral blood flow was found to be similar between experimental groups. Blood flow significantly decreased immediately after injury, returned to baseline by 1 day, and was significantly elevated by 7 days, post-injury. Nonheme iron preferentially accumulated in the ipsilateral cortex, hippocampus, and external capsule in both WT and KO brain-injured genotypes. There were, however, a significantly greater number of TUNEL-positive cells in the hippocampal dentate gyrus and a significantly greater cortical lesion volume in KOs relative to WTs within the first week post-injury. By 14 days post-injury, however, cortical lesion volume and cell density in the hippocampal CA3 region and dorsal thalamus were similar between the two groups. Assays of fine motor function (grip strength) over the first 2 weeks post-injury revealed a general pattern of decreased strength in the contralateral forelimbs of KOs as compared to WTs. Together, these findings demonstrate that deficiency in HO-2 alters both the kinetics of secondary damage and fine motor recovery after TBI.


Assuntos
Lesões Encefálicas/enzimologia , Córtex Cerebral/enzimologia , Heme Oxigenase (Desciclizante)/metabolismo , Hipocampo/enzimologia , Recuperação de Função Fisiológica/fisiologia , Análise de Variância , Animais , Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Contagem de Células , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Circulação Cerebrovascular/fisiologia , Força da Mão/fisiologia , Heme Oxigenase (Desciclizante)/genética , Hipocampo/patologia , Hipocampo/fisiopatologia , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Fluxometria por Laser-Doppler , Masculino , Camundongos , Camundongos Knockout , Atividade Motora/fisiologia , Neurônios/enzimologia , Neurônios/patologia , Teste de Desempenho do Rota-Rod , Fatores de Tempo
11.
Clin Neurosci Res ; 6(5): 283-292, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18059979

RESUMO

The immune response that accompanies spinal cord injury contributes to both injury and reparative processes. It is this duality that is the focus of this review. Here we consider the complex cellular and molecular immune responses that lead to the infiltration of leukocytes and glial activation, promote oxidative stress and tissue damage, influence wound healing, and subsequently modulate locomotor recovery. Immunomodulatory strategies to improve outcomes are gaining momentum as ongoing research carefully dissects those pathways, which likely mediate cell injury from those, which favor recovery processes. Current therapeutic strategies address divergent approaches including early immunoblockade and vaccination with immune cells to prevent early tissue damage and support a wound-healing environment that favors plasticity. Despite these advances, there remain basic questions regarding how inflammatory cells interact in the injured spinal cord. Such questions likely arise as a result of our limited understanding of immune cell/neural interactions in a dynamic environment that culminates in progressive cell injury, demyelination, and regenerative failure.

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