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1.
Pathol Res Pract ; 257: 155311, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38636444

RESUMO

The Silva pattern-based classification of HPV-associated endocervical adenocarcinoma has become an integral part of the histologic assessment of these tumors. Unfortunately, the Silva system reproducibility has had mixed results in past studies, and clinical practice still favors the FIGO stage assessment in directing therapeutic interventions for patients. In our study, we aimed to assess our institution's concordance including not only gynecologic pathologists, but also pathology trainees through a series of 69 cases. The grouped total kappa concordance from all participants was 0.439 (Moderate), with an overall trainee kappa of 0.417 (moderate) and an overall pathologist kappa of 0.460 (moderate). Perfect concordance among all 10 study participants was seen in 8/69 cases (11.6 %), corresponding to 5/22 Pattern A cases (22.7 %), 0/16 Pattern B cases (0 %), and 3/31 Pattern C cases (9.7 %), with similar findings between trainees and pathologists when compared within their own cohorts. Recurrence was identified in 2 Pattern A cases, indicating a potential issue with limited excisional specimens which may not fully appreciate the true biologic aggressiveness of the lesions.


Assuntos
Adenocarcinoma , Infecções por Papillomavirus , Patologistas , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/virologia , Adenocarcinoma/patologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/complicações , Adulto , Pessoa de Meia-Idade , Ginecologia/educação , Reprodutibilidade dos Testes , Variações Dependentes do Observador , Idoso
2.
JAMA Surg ; 158(12): 1265-1273, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37870954

RESUMO

Importance: Oral tamoxifen citrate benefits women with ductal carcinoma in situ (DCIS), but concern about toxic effects has limited acceptance. Previous pilot studies have suggested transdermal 4-hydroxytamoxifen gel has equivalent antiproliferative efficacy to oral tamoxifen, with low systemic exposure. Objective: To demonstrate that 4-hydroxytamoxifen gel applied to the breast skin is noninferior to oral tamoxifen in its antiproliferative effect in DCIS lesions. Design, Setting, and Participants: This randomized, double-blind, phase 2 preoperative window trial was performed at multicenter breast surgery referral practices from May 31, 2017, to January 27, 2021. Among 408 women with estrogen receptor-positive DCIS who were approached, 120 consented and 100 initiated study treatment. The most common reasons for nonparticipation were surgical delay, disinterest in research, and concerns about toxic effects. Data were analyzed from January 26, 2021, to October 5, 2022. Intervention: Random assignment to oral tamoxifen citrate, 20 mg/d, and gel placebo or 4-hydroxytamoxifen gel, 2 mg/d per breast, and oral placebo, for 4 to 10 weeks, followed by DCIS resection. Main Outcomes and Measures: The primary end point was absolute change in DCIS Ki-67 labeling index (Ki67-LI). Secondary end points included 12-gene DCIS Score, breast tissue tamoxifen metabolite concentrations, tamoxifen-responsive plasma protein levels, and patient-reported symptoms. Noninferiority of Ki67-LI reduction by 4-hydroxytamoxifen gel was tested using analysis of covariance; within- and between-arm comparisons were performed with paired t tests for mean values or the Wilcoxon rank sum test for medians. Results: Of 90 participants completing treatment (mean [SD] age, 55 [11] years; 8 [8.9%] Asian, 16 [17.8%] Black, 8 [8.9%] Latina, and 53 [58.9%] White), 15 lacked residual DCIS in the surgical sample, leaving 75 evaluable for the primary end point analysis (40 in the oral tamoxifen group and 35 in the 4-hydroxytamoxifen gel group). Posttreatment Ki67-LI was 3.3% higher (80% CI, 2.1%-4.6%) in the 4-hydroxytamoxifen gel group compared with the oral tamoxifen group, exceeding the noninferiority margin (2.6%). The DCIS Score decreased more with oral tamoxifen treatment (-16 [95% CI, -22 to -9.4]) than with 4-hydroxytamoxifen gel (-1.8 [95% CI, -5.8 to 2.3]). The median 4-hydroxytamoxifen concentrations deep in the breast were nonsignificantly higher in the oral tamoxifen group (5.7 [IQR, 4.0-7.9] vs 3.8 [IQR, 1.3-7.9] ng/g), whereas endoxifen was abundant in the oral tamoxifen group and minimal in the 4-hydroxytamoxifen gel group (median, 13.0 [IQR, 8.9-20.6] vs 0.3 [IQR, 0-0.3] ng/g; P < .001). Oral tamoxifen caused expected adverse changes in plasma protein levels and vasomotor symptoms, with minimal changes in the transdermal group. Conclusions and Relevance: In this randomized clinical trial, antiproliferative noninferiority of 4-hydroxytamoxifen gel to oral tamoxifen was not confirmed, potentially owing to endoxifen exposure differences. New transdermal approaches must deliver higher drug quantities and/or include the most potent metabolites. Trial Registration: ClinicalTrials.gov Identifier: NCT02993159.


Assuntos
Carcinoma Intraductal não Infiltrante , Humanos , Feminino , Pessoa de Meia-Idade , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/cirurgia , Antígeno Ki-67 , Método Duplo-Cego , Tamoxifeno/uso terapêutico , Tamoxifeno/efeitos adversos , Proteínas Sanguíneas/uso terapêutico
3.
Int J Surg Pathol ; : 10668969231189714, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37525567

RESUMO

INTRODUCTION: Histiocytoid lobular breast carcinoma is a rare subtype of invasive lobular carcinoma characterized by relatively bland, uniform nuclei, single small eosinophilic nucleolus, and ample granular cytoplasm. These cancers are typically triple negative, show frequent androgen receptor (AR) positivity, and are therefore theorized to represent a variant of apocrine differentiation in invasive lobular carcinoma. Anecdotal evidence suggests that these tumors have excellent outcomes, though some studies suggest a variable clinical outcome. METHODS: Inclusion criteria included women with a histologic diagnosis of invasive lobular carcinoma with histiocytoid features, regardless of immunohistochemical profile, diagnosed at our institution between 2008 and 2021 with additional tissue still available for ancillary studies. We reviewed patients meeting these criteria and investigated hematoxylin and eosin-stained slides and a panel of immunohistochemical stains (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 [HER2], AR, endothelial growth factor receptor, and keratin 5/6), as well as outcomes including survival and metastatic disease. RESULTS: Overall, 12 eligible patients were identified. The classical immunophenotype (triple negative with AR positivity) was noted in 4 out of 12 tumors. The majority of the remaining tumors (7 out of 12) showed a luminal B immunohistochemical profile, while 1 out of 12 was HER2-enriched. No patients in the cohort died from disease-related causes and 2 out of 12 presented with distant metastatic disease during their disease course. CONCLUSION: Histiocytoid lobular breast carcinoma is a morphologic variant of lobular carcinoma with apocrine features that shows a variable immunohistochemical profile and variable clinical behavior. Further subclassification and stricter diagnostic criteria may be helpful in the distinction between truly indolent tumors and those with more aggressive clinical features.

5.
Ann Surg Oncol ; 30(8): 5215-5224, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36856909

RESUMO

BACKGROUND: The validation of breast cancer risk biomarkers in benign breast samples (BBS) is a long-sought goal, hampered by the fluctuation of gene and protein expression with menstrual phase (MP) and menopausal status (MS). Previously, we identified hormone-related gene expression and histomorphology parameters to classify BBS by MS/MP. We now evaluate both together, to validate our prior results. PATIENTS AND METHODS: BBS were obtained from consenting women (86 premenopausal, 55 postmenopausal) undergoing reduction mammoplasty (RM) or contralateral unaffected breast (CUB) mastectomy. MP/MS was defined using classical criteria for menstrual dates and hormone levels on the day of surgery. BBS gene expression was measured with reverse transcription quantitative polymerase chain reaction (RT-qPCR) for three luteal phase (LP) genes (TNFSF11, DIO2, MYBPC1) and four menopausal genes (PGR, GREB1, TIFF1, CCND1). Premenopausal samples were classified into LP or non-LP, using published histomorphology parameters. Logistic regression and receiver-operator curve analysis was performed to assess area under the curve (AUC) for prediction of MP/MS. RESULTS: In all 131 women, menopausal genes plus age > 50 years predicted true MS [AUC 0.93, 95% confidence interval (CI) 0.89, 0.97]. Among premenopausal women, high TNFSF11 expression distinguished non-LP from LP samples (AUC 0.80, 95% CI 0.70, 0.91); the addition of histomorphology improved the prediction nonsignificantly (AUC 0.87, 95% CI 0.78, 0.96). In premenopausal subsets, addition of histomorphology improved LP prediction in RM (AUC 0.95, 95% CI 0.87, 1.0), but not in CUB (0.84, 95% CI 0.72, 0.96). CONCLUSIONS: Expression of five-gene set accurately predicts menopausal status and menstrual phase in BBS, facilitating the development of breast cancer risk biomarkers using large, archived sample repositories.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Mastectomia , Menopausa/genética , Hormônios , Expressão Gênica , Biomarcadores
6.
Pathol Res Pract ; 244: 154413, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36921545

RESUMO

Pregnancy associated breast cancer (PABC) is defined as a breast cancer diagnosed during gestation, lactation or within 5 years postpartum. While the development of malignancy during pregnancy is rare, the incidence is increasing. Breast cancer is one of the most common cancers diagnosed during pregnancy, affecting up to 1 in 3000 deliveries. New understanding of the pathophysiology of PABC recently resulted in updated definitions distinguishing breast cancer diagnosed during pregnancy (PrBC) from cancer diagnosed during the postpartum period (PPBC) due to distinct biology and prognosis. Pregnancy has a dual effect on breast cancer development- both protective against cancer and promoting tumor growth. While several hypotheses have been proposed over the years to explain these effects, the most likely hypothesis for the development of PABC is the involution hypothesis, proposing that remodeling programs activated in the immediate postpartum period are similar to wound healing and inflammation that may be associated with tumor development and progression. Although PABCs reflect all subtypes of breast carcinomas, they are most commonly invasive ductal carcinomas of high tumor grade and large tumor size, with more advanced stage at presentation and higher rates of lymph node involvement. Most PABCs are hormone negative tumors (triple negative or HER2 amplified tumors) with high Ki-67 proliferation rates. Several studies have shown that PABCs have different genomic signatures than non-PABC tumors, showing increased expression of immune response mediators. Better understanding of the molecular pathways of tumor initiation and progression, along with prompt diagnosis and novel treatment protocols in the care of PrBC and PPBC are needed to improve outcomes for these young, high-risk breast cancer patients.


Assuntos
Neoplasias da Mama , Complicações Neoplásicas na Gravidez , Gravidez , Feminino , Humanos , Neoplasias da Mama/patologia , Complicações Neoplásicas na Gravidez/diagnóstico , Período Pós-Parto , Prognóstico
7.
Pathol Res Pract ; 241: 154299, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36603407

RESUMO

PRAME and NY-ESO-1 are cancer-testis antigens (CTAs) reported to be highly enriched in triple-negative breast cancers (TNBCs), against which vaccines and immunotherapies are currently being developed. This study aims to analyze PRAME and NY-ESO-1 expression in TNBCs and their correlation with clinical outcomes. This is a retrospective cohort study of TNBC patients who have undergone neoadjuvant chemotherapy. PRAME and NY-ESO-1 expression were assessed on pre-therapy biopsies as H-scores (percentage x intensity) with final H scores of 2-3 considered as positive. Association between expression and pathologic complete response (pCR), metastasis, and residual cancer burden (RCB) were assessed via logistic regression. Cox proportional hazards models were used to assess the association with progression-free survival. P-values < 0.05 were considered statistically significant. Sixty-three percent of 76 patients were positive for PRAME. In contrast, only 5 % were positive for NY-ESO-1. PRAME positivity was significantly associated with a lower likelihood of early metastatic disease (OR = 0.24, 95 % CI 0.08-0.62; P = 0.005). However, it was not significantly associated with pCR, RCB category, or progression-free survival. NY-ESO1 score was not significantly associated with early metastatic disease, pCR, RCB category, or progression-free survival. Our results suggest that PRAME positivity may be associated with a lower risk of early metastasis in TNBCs, but not with response to neoadjuvant chemotherapy or progression-free survival. The high expression of PRAME in TNBCs makes it a potential therapeutic target, while NY-ESO1 appears to be a less useful marker. However, further larger studies are needed to ascertain the utility of these markers.


Assuntos
Antígenos de Neoplasias , Neoplasias de Mama Triplo Negativas , Humanos , Masculino , Anticorpos , Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/análise , Prognóstico , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/patologia
8.
Pediatr Dev Pathol ; 26(1): 72-76, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36448449

RESUMO

Somatic malignancies arising in mature teratomas are exceedingly rare entities and even more so are those arising in immature teratomas. Here, we present a unique case of a 13-year-old who initially underwent ovarian sparing cystectomy for a 7.7 cm left ovarian mass with a pre-operative diagnosis of mature cystic teratoma. Histologically, all 3 germ cell layers were present and immature neuroepithelial tubules were also identified. Subsequent sections revealed a nodular lesion composed of neuropil, neuroblasts with a spectrum of maturation, and Schwannian-type stroma. The neuroblasts were diffusely positive for PHOX2B. Neuroblastoma arising in an immature teratoma has only been described in the literature once previously in an adult patient.


Assuntos
Neuroblastoma , Neoplasias Ovarianas , Teratoma , Adulto , Feminino , Humanos , Adolescente , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Teratoma/diagnóstico , Teratoma/cirurgia , Teratoma/patologia , Neuroblastoma/patologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-35577429

RESUMO

INTRODUCTION: Parapharyngeal space (PPS) is defined as a deep space, located around the upper pharynx, in the shape of an inverted pyramid. Primary tumours in this region are rare, accounting for 0.5% of head and neck neoplasms, and most are benign. The objective of this study is to propose a new study algorithm based on a systematic review and our experience. MATERIALS AND METHODS: A cross-sectional and analytical study was carried out through review of the clinical records of our hospital. Patients with tumours of the parapharyngeal space operated from January 2010 to December 2019 and a systematic review of Pubmed studies from the last 5 years were included. We considered clinical signs, diagnostic methods, presumptive diagnosis and histopathological findings. Statistical analysis was performed with STATA v.14 software. RESULTS: 53 of our cases and 1392 from the review were included. The clinical algorithm showed a sensitivity of 76.4% and a specificity of 96.3%, with an AUC of 0.57 for diagnosis. DISCUSSION: Complementary radiological examinations are essential in the topographic diagnosis of the tumour. Angio-MRI links the tissue of origin of the tumours and provides the highest diagnostic certainty. FNA has some disadvantages in PPS, but it is useful in some patients. CONCLUSION: The proposed algorithm contributes to obtaining excellent results in the management of these tumours because it turned out to be effective in diagnosis, and this enables improved surgical planning.


Assuntos
Neoplasias de Cabeça e Pescoço , Espaço Parafaríngeo , Algoritmos , Estudos Transversais , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Estudos Retrospectivos
11.
Artigo em Inglês | MEDLINE | ID: mdl-35190087

RESUMO

INTRODUCTION: The most common cause of deep neck infections is dental infection. They are diagnosed with physical examination, imaging studies, ultrasound, or computed tomography. Surgical drainage of collections should always be performed early in a classical or percutaneous way, depending on the case. The aim of the study was to compare ultrasound-guided percutaneous drainage techniques vs. surgical drainage in deep cervical abscesses of odontogenic origin in a controlled and randomized trial. METHODS: A randomized controlled clinical trial was performed from January 2015 to December 2019. Hospital stay was evaluated as an efficiency variable. Epidemiological and secondary variable data (tumour, trismus, fever, pain), leukocytosis, cosmetic result comparing both techniques were analysed. Statistical analysis was carried out with STATA v 14.0. RESULTS: 128 patients were analysed, 51 women and 77 men. Average age 27.3 (SD = 10.13). The percutaneous group had a mean hospital stay of 3.03 (SD = 2.86) days and the surgical group 5.46 (SD = 2.96). The P-value was <.001. Cosmetic results showed differences favouring the percutaneous drainage group. None of the other variables showed statistically significant results. DISCUSSION: Surgical treatment (cervicotomy and debridement) should be undertaken early with evidence of extensive collection in deep spaces. Minimally invasive image-guided procedures are an alternative. These can be performed in well-located, unilocular collections, without compromising of the patient's airway. Percutaneous drainage and suction techniques if necessary, serially, or drainage placement may be performed. CONCLUSIONS: Ultrasound-guided and serially guided percutaneous drainage is the best therapeutic option in patients with mild and/or moderate dental infections.


Assuntos
Abscesso , Drenagem , Abscesso/diagnóstico por imagem , Abscesso/cirurgia , Adulto , Feminino , Humanos , Masculino , Pescoço/cirurgia , Ultrassonografia , Ultrassonografia de Intervenção/métodos
12.
Oncotarget ; 13: 273-280, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35126865

RESUMO

BACKGROUND: The correlation of ERBB2 copy number gain (CNG) from tissue or circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) with standard HER2 tissue evaluation is not well understood. MATERIALS AND METHODS: We retrospectively identified patients with ERBB2 CNG on commercial NGS. We described their clinical-pathologic features and calculated the positive predictive value (PPV) of ERBB2 CNG by NGS for HER2-positivity by IHC and FISH testing. RESULTS: 176 patients had NGS revealing an ERBB2 CNG (112 by tumor tissue and 91 by ctDNA). The cancer subtypes with the most cases with ERBB2 CNG by NGS were breast (n = 67), non-small cell lung (n = 25), colorectal (n = 18), gastroesophageal (n = 17), pancreatic (n = 11), and uterine (n = 11). The PPV of ERBB2 CNG in determining HER2 positivity by standard IHC/FISH definitions was 88% for tissue NGS (n = 57) and 80% for ctDNA (n = 47). The PPV among breast cancer patients for tissue NGS was 97% (n = 35) and ctDNA was 93% (n = 39). However, for non-breast cancer cases, the PPV of ERBB2 amplification by tissue NGS dropped to 76% (n = 22) and by ctDNA to 44% (n = 7). CONCLUSIONS: ERBB2 CNG by NGS is detected in numerous malignancies for which HER2 testing is not standard. Detection of ERBB2 CNG by tissue NGS and ctDNA has a high PPV for true HER2-positivity by standard IHC and/or FISH testing in breast cancer.


Assuntos
DNA Tumoral Circulante , Neoplasias , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Variações do Número de Cópias de DNA , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Valor Preditivo dos Testes , Receptor ErbB-2/genética , Estudos Retrospectivos
13.
Breast Dis ; 41(1): 55-65, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34397396

RESUMO

BACKGROUND: Ki-67 immunohistochemistry (IHC) staining is a widely used cancer proliferation assay; however, its limitations could be improved with automated scoring. The OncotypeDXTM Recurrence Score (ORS), which primarily evaluates cancer proliferation genes, is a prognostic indicator for breast cancer chemotherapy response; however, it is more expensive and slower than Ki-67. OBJECTIVE: To compare manual Ki-67 (mKi-67) with automated Ki-67 (aKi-67) algorithm results based on manually selected Ki-67 "hot spots" in breast cancer, and correlate both with ORS. METHODS: 105 invasive breast carcinoma cases from 100 patients at our institution (2011-2013) with available ORS were evaluated. Concordance was assessed via Cohen's Kappa (κ). RESULTS: 57/105 cases showed agreement between mKi-67 and aKi-67 (κ 0.31, 95% CI 0.18-0.45), with 41 cases overestimated by aKi-67. Concordance was higher when estimated on the same image (κ 0.53, 95% CI 0.37-0.69). Concordance between mKi-67 score and ORS was fair (κ 0.27, 95% CI 0.11-0.42), and concordance between aKi-67 and ORS was poor (κ 0.10, 95% CI -0.03-0.23). CONCLUSIONS: These results highlight the limits of Ki-67 algorithms that use manual "hot spot" selection. Due to suboptimal concordance, Ki-67 is likely most useful as a complement to, rather than a surrogate for ORS, regardless of scoring method.


Assuntos
Automação Laboratorial/estatística & dados numéricos , Automação Laboratorial/normas , Neoplasias da Mama/secundário , Imuno-Histoquímica/estatística & dados numéricos , Imuno-Histoquímica/normas , Antígeno Ki-67/análise , Mama/patologia , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica/métodos , Pessoa de Meia-Idade , Prognóstico
14.
Altern Ther Health Med ; 28(8): 8-15, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33421040

RESUMO

Context: Epidemiological evidence has shown that lycopene consumption may be effective in both the prevention and treatment of various diseases, particularly prostate cancer. However, the influence of this dietary carotenoid on some of the most basic aspects of human health remains unknown. Objectives: The aim of the study was to determine the effects of consumption of a lycopene-enriched commercial product of organic, extra virgin olive oil (EVOO) on prostate health, sleep quality, antioxidant status, and anxiety. Design: The research team designed a pilot study with two intervention groups. Setting: The study took place in the city of Badajoz (Extremadura, Spain). Participants: Participants were 20 men aged ≥50, some of whom were healthy and some of whom had received a diagnosis of benign prostatic hyperplasia. Intervention: Participants were divided into a healthy-men (HM) group (n = 10) and a benign prostatic hyperplasia (BPH) group (n = 10). Both groups consumed 20 ml of lycopene (0.4 mg/ml) daily in a lycopene-enriched commercial product of organic extra virgin olive oil, at breakfast and/or lunch, for 30 days. Outcome Measures: Sleep quality, prostate markers-prostatic specific antigen and protein C reactive-and symptomatology, urine total antioxidant status, and emotional health were assessed at baseline and postintervention. Results: The level of prostatic specific antigen and symptomatology remarkably improved in men with benign prostatic hyperplasia, although the changes wasn't statistically significant, and the total antioxidant status was significantly increased in healthy men (P < .05). Sleep quality in terms of nocturnal activity was significantly improved in both groups (P < .05). No adverse events were reported. Conclusion: The consumption of a lycopene-enriched, organic, EVOO positively influenced prostate health and other physiological variables. These findings may help to advance the development of new preventive and/or chemotherapeutic strategies based on lycopene.


Assuntos
Hiperplasia Prostática , Masculino , Humanos , Licopeno/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/prevenção & controle , Azeite de Oliva/uso terapêutico , Projetos Piloto , Antioxidantes/uso terapêutico
15.
Int J Mol Sci ; 22(19)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34638604

RESUMO

The nano-sized membrane enclosed extracellular vesicles (EVs) released by virtually all cell types play an essential role in intercellular communication via delivering bio-molecules, such as nucleic acids, proteins, lipids, and other molecules to recipient cells. By mediating an active and steady-state cell-to-cell communication, EVs contribute to regulating and preserving cellular homeostasis. On the other hand, EVs can also spread pathogen-derived molecules during infections, subverting the host immune responses during infections and thus worsening pathophysiological processes. In recent years, the biological functioning of EVs has become a widespread research field in basic and clinical branches of medical sciences due to their potential role in therapeutic applications for several diseases. This review aims to summarize the main recent findings regarding the implication of EVs shed by human macrophages (MΦ-EVs) and how they can modulate the host immune response to control or increase the damage caused by infectious agents. We will also present the methods used to describe MΦ-EVs, as well as the potential of these EVs as disease diagnostic tools for some human pathogens. We believe that an in-depth understanding of the host-pathogen interactions mediated by MΦ-EVs may trigger the development of innovative therapeutic strategies against infectious diseases.


Assuntos
Vesículas Extracelulares/fisiologia , Interações Hospedeiro-Patógeno/fisiologia , Macrófagos/fisiologia , Comunicação Celular/fisiologia , Doenças Transmissíveis/patologia , Doenças Transmissíveis/fisiopatologia , Humanos
16.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34301374

RESUMO

INTRODUCTION: The most common cause of deep neck infections is dental infection. They are diagnosed with physical examination, imaging studies, ultrasound, or computed tomography. Surgical drainage of collections should always be performed early in a classical or percutaneous way, depending on the case. The aim of the study was to compare ultrasound-guided percutaneous drainage techniques vs. surgical drainage in deep cervical abscesses of odontogenic origin in a controlled and randomized trial. METHODS: A randomized controlled clinical trial was performed from January 2015 to December 2019. Hospital stay was evaluated as an efficiency variable. Epidemiological and secondary variable data (tumour, trismus, fever, pain), leukocytosis, cosmetic result comparing both techniques were analysed. Statistical analysis was carried out with STATA v 14.0. RESULTS: 128 patients were analysed, 51 women and 77 men. Average age 27.3 (SD = 10.13). The percutaneous group had a mean hospital stay of 3.03 (SD = 2.86) days and the surgical group 5.46 (SD = 2.96). The p-value was <.001. Cosmetic results showed differences favouring the percutaneous drainage group. None of the other variables showed statistically significant results. DISCUSSION: Surgical treatment (cervicotomy and debridement) should be undertaken early with evidence of extensive collection in deep spaces. Minimally invasive image-guided procedures are an alternative. These can be performed in well-located, unilocular collections, without compromising of the patient's airway. Percutaneous drainage and suction techniques if necessary, serially, or drainage placement may be performed. CONCLUSIONS: Ultrasound-guided and serially guided percutaneous drainage is the best therapeutic option in patients with mild and/or moderate dental infections.

17.
Nucleic Acids Res ; 49(14): 8199-8213, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34302490

RESUMO

PrimPol is the second primase in human cells, the first with the ability to start DNA chains with dNTPs. PrimPol contributes to DNA damage tolerance by restarting DNA synthesis beyond stalling lesions, acting as a TLS primase. Multiple alignment of eukaryotic PrimPols allowed us to identify a highly conserved motif, WxxY near the invariant motif A, which contains two active site metal ligands in all members of the archeo-eukaryotic primase (AEP) superfamily. In vivo and in vitro analysis of single variants of the WFYY motif of human PrimPol demonstrated that the invariant Trp87 and Tyr90 residues are essential for both primase and polymerase activities, mainly due to their crucial role in binding incoming nucleotides. Accordingly, the human variant F88L, altering the WFYY motif, displayed reduced binding of incoming nucleotides, affecting its primase/polymerase activities especially during TLS reactions on UV-damaged DNA. Conversely, the Y89D mutation initially associated with High Myopia did not affect the ability to rescue stalled replication forks in human cells. Collectively, our data suggest that the WFYY motif has a fundamental role in stabilizing the incoming 3'-nucleotide, an essential requisite for both its primase and TLS abilities during replication fork restart.


Assuntos
DNA Primase/genética , Replicação do DNA/genética , DNA Polimerase Dirigida por DNA/genética , DNA/genética , Enzimas Multifuncionais/genética , Motivos de Aminoácidos/genética , DNA/biossíntese , Dano ao DNA/genética , Humanos , Proteína FUS de Ligação a RNA/genética
18.
Prensa méd. argent ; 107(5): 276-281, 20210000. fig
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1359360

RESUMO

La lesión del nervio laríngeo recurrente (NLR) es una de las complicaciones más severas en las tiroidectomías. La lesión unilateral genera trastornos disfónicos que se manifiesta por voz débil y una posición paramedial de la cuerda vocal afectada, mientas que la bilateral genera trastornos respiratorios, incluyendo la asfixia. Se ha estimado que la lesión del NLR en las tiroidectomías se encuentra entre un rango de 0.3%- 18.9%. Se ha visto que con el neuromonitoreo intraoperatorio ha disminuido la incidencia de lesión, aunque debemos tener en cuenta un factor muy importante a la hora de solicitarlo y utilizarlo, el económico. La tasa de lesión permanente del nervio laríngeo recurrente debe permanecer por debajo de 1 a 2 %. Sin embargo, existen circunstancias en las cuales los nervios están expuestos a un mayor riesgo y son muchos los factores involucrados en su mecanismo de lesión. Este artículo pretende hacer una revisión del tema enfatizando en la importancia de la preservación de la funcionalidad e integridad de ambos nervios laríngeos recurrentes.


Recurrent laryngeal nerve injury (RLN) is one of the most severe complications in thyroidectomies. Unilateral injury generates dysphonic disorders manifested by weak voice and a paramedial position of the affected vocal cord, while bilateral injury generates respiratory disorders, including suffocation. RLN injury in thyroidectomies has been estimated to be in the range of 0.3% - 18.9%. It has been seen that with intraoperative neuromonitoring the incidence of injury has decreased, although we must take into account a very important factor when requesting and using it, the economic one. The rate of permanent injury to the recurrent laryngeal nerve should remain below 1% to 2%. However, there are circumstances in which the nerves are exposed to greater risk and many factors are involved in their mechanism of injury. This article aims to review the subject, emphasizing the importance of preserving the functionality and integrity of both recurrent laryngeal nerves


Assuntos
Humanos , Nervo Laríngeo Recorrente/patologia , Tireoidectomia , Neoplasias da Glândula Tireoide/complicações , Monitorização Intraoperatória
19.
Pathol Res Pract ; 222: 153441, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33857853

RESUMO

Human epidermal growth factor receptor 2 (HER2) overexpression occurs in 15-20 % of all breast carcinomas. These tumors are usually high-grade which often correlates with reduced overall survival and increased rates of recurrence. In a retrospective review, we identified 19 cases of unexpectedly HER2 positive (by immunohistochemistry and/or fluorescence in-situ hybridization) invasive breast carcinomas on core needle biopsies from a registry at Northwestern Memorial Hospital. These cases included low-grade tumors, invasive lobular carcinomas, classic type, and invasive carcinomas with special subtype features. Twelve of the tumors were histologic grade 1 and 7 were histologic grade 2. One of the grade 1 tumors had tubular features (8 %), 1 had cribriform features (8 %), 2 had mucinous features (17 %), 2 were invasive lobular carcinomas, classic type (17 %), and the rest were invasive carcinoma, no special type (50 %). The histologic grade 2 tumors included 5 invasive lobular carcinomas, classic type (71 %) and 2 invasive ductal carcinomas with mucinous features (29 %). By immunohistochemistry, 13 (65 %) were HER2 score 3+, 7 were score 2+ (35 %), and reflex fluorescence in-situ hybridization (FISH) testing showed amplification in 6 cases, with 1 equivocal case amplified on excision. Despite the HER2 positive status in the selected cases, no unique morphologic features that would indicate aggressive behavior were identified. In clinical follow up, two patients were found to have recurrences, five had lymph node metastasis, and one had distant metastasis. None of the patients with recurrent disease were treated with trastuzumab, despite their positive HER2 results. These findings support that our population of HER2 positive carcinomas showed a similar rate of lymph node metastases and recurrence as poorly-differentiated tumors, supporting HER2 positivity as a poor prognostic indicator, irrespective of morphologic features. We recommend continuing to test all breast cancers, regardless of grade or special subtype features, to provide the most comprehensive treatment and prognostic information for both clinicians and patients.


Assuntos
Neoplasias da Mama/patologia , Metástase Linfática/patologia , Recidiva Local de Neoplasia/patologia , Receptor ErbB-2/metabolismo , Adulto , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Amplificação de Genes/fisiologia , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Prognóstico
20.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33810827

RESUMO

INTRODUCTION: Parapharyngeal space (PPS) is defined as a deep space, located around the upper pharynx, in the shape of an inverted pyramid. Primary tumours in this region are rare, accounting for 0.5% of head and neck neoplasms, and most are benign. The objective of this study is to propose a new study algorithm based on a systematic review and our experience. MATERIALS AND METHODS: A cross-sectional and analytical study was carried out through review of the clinical records of our hospital. Patients with tumours of the parapharyngeal space operated from January 2010 to December 2019 and a systematic review of Pubmed studies from the last 5years were included. We considered clinical signs, diagnostic methods, presumptive diagnosis and histopathological findings. Statistical analysis was performed with STATA v.14 software. RESULTS: 53 of our cases and 1392 from the review were included. The clinical algorithm showed a sensitivity of 76.4% and a specificity of 96.3%, with an AUC of 0.57 for diagnosis. DISCUSSION: Complementary radiological examinations are essential in the topographic diagnosis of the tumour. Angio-MRI links the tissue of origin of the tumours and provides the highest diagnostic certainty. FNA has some disadvantages in PPS, but it is useful in some patients. CONCLUSION: The proposed algorithm contributes to obtaining excellent results in the management of these tumours because it turned out to be effective in diagnosis, and this enables improved surgical planning.

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