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1.
Science ; 366(6465)2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31672865

RESUMO

As people age, their tissues accumulate an increasing number of somatic mutations. Although most of these mutations are of little or no functional consequence, a mutation may arise that confers a fitness advantage on a cell. When this process happens in the hematopoietic system, a substantial proportion of circulating blood cells may derive from a single mutated stem cell. This outgrowth, called "clonal hematopoiesis," is highly prevalent in the elderly population. Here we discuss recent advances in our knowledge of clonal hematopoiesis, its relationship to malignancies, its link to nonmalignant diseases of aging, and its potential impact on immune function. Clonal hematopoiesis provides a glimpse into the process of mutation and selection that likely occurs in all somatic tissues.


Assuntos
Envelhecimento , Doenças Cardiovasculares/genética , Neoplasias Hematológicas/genética , Hematopoese , Células-Tronco Hematopoéticas/fisiologia , Mutação , Lesões Pré-Cancerosas/genética , Idoso , Animais , Doenças Cardiovasculares/fisiopatologia , Evolução Clonal , Células Clonais , Neoplasias Hematológicas/fisiopatologia , Células-Tronco Hematopoéticas/citologia , Humanos , Lesões Pré-Cancerosas/fisiopatologia
2.
Biomed Res Int ; 2019: 5219048, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31312658

RESUMO

Introduction: Glans resurfacing has been suggested as a treatment option for the surgical management of superficial penile cancer (Tis, Ta, T1aG1, T1aG2). In this article we describe in detail the glans resurfacing technique with skin graft for penile cancer in a video presentation and we review the current knowledge of the literature. Material and Methods: The procedure is described in a stepwise fashion. Initially the patient is circumcised. The glans is marked in quadrants and completely stripped by dissecting and removing the epithelium and subepithelium layer of the glans. Deep spongiosal biopsies are taken to exclude invasion. Each quadrant is sent separately for biopsy. The surface of the graft size needed is estimated. A partial thickness skin graft is harvested from the thigh with a dermatome. The skin graft is then fenestrated. The graft is rolled over the glans and quilted with multiple sutures. A silicone 16F Foley catheter and a suprapubic catheter are placed. The penis is dressed with multiple gauzes and compressed with an elastic band. Results: The patient is discharged the next day. The dressing and Foley catheter are removed in 7 days. The patient continues to use the suprapubic catheter for 7 more days. The patient refrains from any sexual activity for 6 weeks and is closely followed. Conclusions: Glans resurfacing is an emerging new appealing surgical technique that is already a recommendation in the EAU guidelines for the treatment of premalignant and superficial penile lesions. The overall satisfaction rate and recovery of the sexual function are acceptable, and it can be considered an ideal procedure to treat superficial penile cancer.


Assuntos
Neoplasias Penianas/cirurgia , Pênis/transplante , Lesões Pré-Cancerosas/cirurgia , Transplante de Pele , Humanos , Masculino , Neoplasias Penianas/fisiopatologia , Pênis/fisiopatologia , Lesões Pré-Cancerosas/fisiopatologia , Procedimentos Cirúrgicos Reconstrutivos , Pele/fisiopatologia , Transplantes , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos Masculinos
3.
Semin Liver Dis ; 39(3): 315-333, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31226725

RESUMO

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. A unique feature of liver cancer is its close association with liver fibrosis. About 90% of HCCs develop in advanced liver fibrosis or cirrhosis, suggesting an important role for the fibrotic microenvironment in driving HCC development. Here, the authors will discuss functional contributions of liver fibrosis to the development of HCC, focusing on mechanisms through which fibrosis may promote HCC development such as hepatic stellate cell-derived extracellular matrix, growth factors, and cytokines, stiffness-induced signaling pathways, and immunosuppression. Better understanding of these factors in HCC development and progression may provide the basis for novel stromal-based therapies for tumor prevention or therapy.


Assuntos
Carcinogênese , Carcinoma Hepatocelular/patologia , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Lesões Pré-Cancerosas/patologia , Animais , Carcinoma Hepatocelular/fisiopatologia , Citocinas/metabolismo , Elasticidade , Células Estreladas do Fígado , Humanos , Inflamação/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Cirrose Hepática/fisiopatologia , Neoplasias Hepáticas/fisiopatologia , Mecanotransdução Celular , Neovascularização Patológica/metabolismo , Lesões Pré-Cancerosas/fisiopatologia , Microambiente Tumoral
4.
Rofo ; 191(8): 725-731, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30703823

RESUMO

GOAL: In order to ensure high-quality cooperation between referring physicians and imaging services, it is important to assess the quality of imaging services as perceived by referring physicians. The present study aimed to develop and validate a questionnaire for referring physicians to assess the quality of outpatient diagnostic imaging services. MATERIALS & METHODS: The questionnaire was developed by discussing and modifying an existing instrument by the German Association of Surgeons. After qualitative pretesting, the instrument was tested with physicians referring to four outpatient diagnostic imaging services in Switzerland. The results were first assessed using descriptive statistics. The final instrument was tested for validity using the concept of known-groups validity. The hypothesis underlying this procedure was that physicians referring frequently to services estimated the quality of these services to be higher than physicians who referred less often to services. The differences in ratings were assessed using a one-sided two-sample Wilcoxon test. The final questionnaire was tested for internal consistency and reliability using Cronbach's Alpha. RESULTS: Results show a high level of satisfaction of referring physicians with the relevant services but also potential for quality improvement initiatives. The psychometric evaluation of the final questionnaire shows that it is a valid instrument, showing significant differences between the ratings of physicians referring with high and low frequency. Furthermore, the instrument proves to be consistent and reliable. CONCLUSION: The final instrument presents a valid, consistent and reliable option for assess the quality of outpatient diagnostic imaging services as perceived by referring physicians. Results can be used as a basis for quality improvement. KEY POINTS: · A newly developed questionnaire assesses the quality of outpatient diagnostic imaging services as perceived by referring physicians. The questionnaire was developed and tested in Switzerland.. · Psychometric evaluation showed the questionnaire to be a valid, consistent and reliable instrument.. · Results are of interest for imaging services as well as for initiatives encompassing several services.. CITATION FORMAT: · Jossen M, Valeri F, Heilmaier C et al. Referring Physicians Assess the Quality of Outpatient Diagnostic Imaging Services: Development and Psychometric Evaluation of a Questionnaire. Fortschr Röntgenstr 2019; 191: 725 - 731.


Assuntos
Imagem de Perfusão/estatística & dados numéricos , Imagem de Perfusão/normas , Psicometria/estatística & dados numéricos , Garantia da Qualidade dos Cuidados de Saúde/normas , Inquéritos e Questionários/estatística & dados numéricos , Inquéritos e Questionários/normas , Assistência Ambulatorial/normas , Assistência Ambulatorial/estatística & dados numéricos , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico/normas , Tomografia Computadorizada de Feixe Cônico/estatística & dados numéricos , Diagnóstico Diferencial , Humanos , Aumento da Imagem/métodos , Aumento da Imagem/normas , Cirrose Hepática/diagnóstico por imagem , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Lesões Pré-Cancerosas/diagnóstico por imagem , Lesões Pré-Cancerosas/fisiopatologia , Garantia da Qualidade dos Cuidados de Saúde/estatística & dados numéricos , Encaminhamento e Consulta/normas , Encaminhamento e Consulta/estatística & dados numéricos , Fluxo Sanguíneo Regional/fisiologia
5.
Genes Dev ; 33(3-4): 127-143, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30709901

RESUMO

Originally thought of as a stress response end point, the view of cellular senescence has since evolved into one encompassing a wide range of physiological and pathological functions, including both protumorignic and antitumorigenic features. It has also become evident that senescence is a highly dynamic and heterogenous process. Efforts to reconcile the beneficial and detrimental features of senescence suggest that physiological functions require the transient presence of senescent cells in the tissue microenvironment. Here, we propose the concept of a physiological "senescence life cycle," which has pathological consequences if not executed in its entirety.


Assuntos
Ciclo Celular/fisiologia , Senescência Celular/fisiologia , Neoplasias/fisiopatologia , Microambiente Celular/fisiologia , Epigenômica , Humanos , Lesões Pré-Cancerosas/fisiopatologia , Encurtamento do Telômero
6.
J Voice ; 33(3): 382.e11-382.e20, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29198815

RESUMO

The aim of the study was comparison of voice and life quality after microdirect laryngoscopy in three patient histopathological categories: benign, precancerous, and malignant glottic lesions. A totalnof 137 patients treated with microdirect laryngoscopy were included in the study. Each patient was evaluated with a multidimensional protocol before and 3, 6, and 12 months after treatment. Final 1-year evaluations were achieved in 74.5% (102). The assessment included laryngovideostroboscopy (LVS), perceptual (GRBAS) grading, aerodynamic measures including maximum phonation time and phonation quotient and acoustic measurements (Kay Elemetrics Multi-Speech program), Voice Handicap Index (VHI), Voice-Related Quality of Life questionnaire; and World Health Organization Quality of Life Scale-Brief Version (WHOQoL-BREF). An improvement in mean value of LVS ratings was obtained in all three groups; however, only in benign lesion group was it consistently statistically significant for each time period (P < 0.001). Perceptual evaluation revealed significant improvement of G, R, and B parameters in benign lesions for each time period. In malignant neoplasms R and B parameters improved 3 and 6 months post microsurgery. In patients with benign lesions the maximum phonation time increased, but the improvement was significant only after 3 months. The acoustic parameters improved in all three groups. VHI significantly improved in patients with benign lesions after 3 and 12 months. VHI in the malignant neoplasm group significantly worsened on the first follow-up visit. Considering quality of life (QoL) results, only in patients with benign lesions was there a significant improvement in overall assessment of their QoL and general health.


Assuntos
Glote/cirurgia , Doenças da Laringe/cirurgia , Neoplasias Laríngeas/cirurgia , Laringoscopia/métodos , Fonação , Lesões Pré-Cancerosas/cirurgia , Qualidade de Vida , Distúrbios da Voz/etiologia , Qualidade da Voz , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Glote/fisiopatologia , Nível de Saúde , Humanos , Doenças da Laringe/complicações , Doenças da Laringe/diagnóstico , Doenças da Laringe/fisiopatologia , Neoplasias Laríngeas/complicações , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/fisiopatologia , Laringoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/complicações , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/fisiopatologia , Estudos Prospectivos , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento , Distúrbios da Voz/diagnóstico , Distúrbios da Voz/fisiopatologia , Adulto Jovem
7.
Acta Clin Croat ; 58(4): 627-631, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32595247

RESUMO

The aim of our study was to determine the prevalence of endometrial premalignant and malignant lesions in women undergoing hysteroscopy and to identify anthropologic factors related to the presence of malignancy. Data on 3470 women with submucosal myomas or endometrial polyps suspected on ultrasound were retrospectively analyzed. Hysteroscopy was performed in all these women in order to make a more precise diagnosis. Histologic analysis of endometrial samples obtained during hysteroscopy was used to confirm the diagnosis. Statistical analysis was performed using the SPSS 20.0.0 software. The mean age of study women was 49.1±13.3 years. The number of procedures performed due to the referral diagnosis of endometrial or submucosal myoma significantly increased over the 16-year study period. A significantly higher number of women had a benign histopathologic diagnosis. Histologic analysis revealed malignancy in 67 women. The youngest woman and oldest woman with malignant findings was aged 32 and 75, respectively. A significantly higher number of women with atypical hyperplasia and malignancy were in menopause. A comparable number of women with different histologic findings lived in urban and rural areas. There were a significantly larger proportion of widows among women with the histologic diagnosis of atypical hyperplasia or malignancy. The prevalence rate of malignancy in women having undergone hysteroscopy for polyps and myoma found by ultrasound was 1.93%. Postmenopausal status and older age were associated with an increased risk of malignancies, but premalignant changes and malignancies were also found in young and premenopausal women. Therefore, diagnostic hysteroscopy can be recommended in women of all age groups.


Assuntos
Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/cirurgia , Mioma/diagnóstico , Mioma/cirurgia , Pólipos/diagnóstico , Pólipos/cirurgia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/fisiopatologia , Feminino , Humanos , Histeroscopia/métodos , Pessoa de Meia-Idade , Mioma/fisiopatologia , Pólipos/fisiopatologia , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/fisiopatologia , Lesões Pré-Cancerosas/cirurgia , Prevalência , Estudos Retrospectivos , Ultrassonografia/métodos , Neoplasias Uterinas/fisiopatologia , Adulto Jovem
8.
Acta Biomed ; 89(8-S): 53-57, 2018 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-30561418

RESUMO

Methods for the measure of gastric acid secretion include invasive and non-invasive tests. The gold-standard to measure the acid output is the collection of gastric after in basal condition (Basal Acid Output, B.A.O.) and after an i.m. injection of pentagastrin (Maximal Acid Output, M.A.O.). However, direct measurement of gastric acid production is out of order in clinical practice, but many GI symptoms are claimed to be related with acid disorders and empirically cured. Hypochlorhydria is associated with precancerous conditions such as chronic atrophic gastritis (CAG). Acid measurement with non-invasive methods (pepsinogens) is supported by international guidelines.


Assuntos
Acloridria/diagnóstico , Determinação da Acidez Gástrica , Gastrinas/sangue , Pepsinogênios/sangue , Acloridria/sangue , Acloridria/fisiopatologia , Biomarcadores , Ácido Gástrico/metabolismo , Gastrite Atrófica/sangue , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/fisiopatologia , Humanos , Pentagastrina/farmacologia , Úlcera Péptica/fisiopatologia , Lesões Pré-Cancerosas/sangue , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/fisiopatologia
11.
Photodiagnosis Photodyn Ther ; 21: 28-35, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29113960

RESUMO

BACKGROUND: We report on a Phase 1 trial of photodynamic therapy (PDT) for superficial head and neck (H&N) lesions. Due to known oxygen dependencies of PDT, translational measurements of lesion hemoglobin oxygen saturation (StO2) and blood volume (tHb) were studied for associations with patient outcomes. METHODS: PDT with aminolevulinc acid (ALA) and escalating light doses was evaluated for high-grade dysplasia, carcinoma-in-situ, and microinvasive carcinomas of the H&N. Among 29 evaluable patients, most (18) had lesions of the tongue or floor of mouth (FOM). Disease was intact in 18 patients and present at surgical margins in 11 patients. In 26 patients, lesion StO2 and tHb was measured. RESULTS: Local control (LC) at 24 months was 57.5% among all patients. In patients with tongue/FOM lesions LC was 42.7%, and it was 50.1% for those with intact lesions. Lesion tHb was not associated with 3-month complete response (CR), but StO2 was higher in patients with CR. In tongue/FOM lesions, baseline StO2 [mean(SE)] was 54(4)% in patients (n=12) with CR versus 23(8)% in patients (n=6) with local recurrence/persistence (p=0.01). Similarly, for intact disease, baseline StO2 was 54(3)% in patients (n=10) with CR versus 28(8)% in patients (n=5) without CR (p=0.03). In patients with intact disease, higher baseline StO2 associated with 24-month local control (p=0.02). CONCLUSIONS: Measurement of the physiologic properties of target lesions may allow for identification of patients with the highest probability of benefiting from PDT. This provides opportunity for optimizing light delivery based on lesion characteristics and/or informing ongoing clinical decision-making in patients who would most benefit from PDT.


Assuntos
Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/fisiopatologia , Hipóxia/fisiopatologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Ácido Aminolevulínico , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/fisiopatologia , Humanos , Lasers Semicondutores/uso terapêutico , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/fisiopatologia , Doses de Radiação
12.
Gut Liver ; 12(2): 158-164, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-28918609

RESUMO

Background/Aims: Gastric juice plays a crucial role in the physiology of the stomach. The aim of this study is to evaluate associations among the pH of gastric juice, atrophic gastritis (AG), intestinal metaplasia (IM), pepsinogen, and Helicobacter pylori infection. Methods: Gastric biopsies and juice were collected from 46 subjects who underwent endoscopies at Seoul National University Bundang Hospital between November 2011 and March 2013. H. pylori, AG and IM were evaluated, and pepsinogen I or II, I/II ratio, and interleukin (IL)-1ß levels were measured. Results: The mean pH of gastric juice was higher in the H. pylori-positive group (n=17) than that in the H. pylori-negative group (n=29) (4.54 vs 2.46, p=0.002). When patients were divided into pH <3 (n=28) and pH ≥3 (n=18) groups, H. pylori was lower in the pH <3 group (21.4%) than in the pH ≥3 group (61.1%) (p=0.007). The pH ≥3 group demonstrated AG and IM more frequently than the pH <3 group in the body (p=0.047 and p=0.051, respectively) but not in the antrum. There were no differences in pepsinogen I or II, I/II ratio, and IL-1ß levels between the two groups. Conclusions: There is a relationship between chronic H. pylori infection and gastric juice pH ≥3, which may originate from AG and IM in the body.


Assuntos
Suco Gástrico/química , Gastrite Atrófica , Helicobacter pylori/isolamento & purificação , Mucosa Intestinal/patologia , Pepsinogênio A/análise , Lesões Pré-Cancerosas , Adulto , Idoso , Feminino , Gastrite Atrófica/epidemiologia , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/patologia , Humanos , Concentração de Íons de Hidrogênio , Masculino , Metaplasia , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/fisiopatologia , República da Coreia , Estatística como Assunto , Neoplasias Gástricas/prevenção & controle
13.
Nutr Clin Pract ; 32(5): 588-598, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28817367

RESUMO

With slowly increasing survival rates in pancreatic cancer and international consensus guidelines recommending surgical resection of premalignant lesions, survival post-pancreatic resection is increasing. With longer survival time, the significant comorbidities of such major surgery have far-reaching effects on the nutrition status of the survivor of pancreatic cancer. This review describes the many nutrition-related side effects of pancreatic surgery, including the development of pancreatic enzyme insufficiency, micronutrient deficiencies, diabetes, fatty liver, and metabolic bone disease. Beyond causing additional medical problems, each of these can have significant effects on quality of life and functional status. The potential mechanisms, diagnosis criteria, and potential treatments of these conditions are described. Overall, little literature exists to fully describe the effects of these comorbidities, and even less is able to guide effective treatments for this population. Clinicians caring for these patients should begin incorporating goals for promotion of long-term health and reduction of these known and reported comorbidities in patients who have undergone pancreatic surgery. Treatment plans in this population remain understudied, and clinicians may need to consider recommendations for similar disease states when developing interventions for these patients.


Assuntos
Apoio Nutricional , Pâncreas/cirurgia , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias/terapia , Sobreviventes , Doenças Ósseas Metabólicas/diagnóstico , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/prevenção & controle , Doenças Ósseas Metabólicas/terapia , Terapia Combinada/efeitos adversos , Deficiências Nutricionais/diagnóstico , Deficiências Nutricionais/etiologia , Deficiências Nutricionais/prevenção & controle , Deficiências Nutricionais/terapia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/etiologia , Diabetes Mellitus/prevenção & controle , Diabetes Mellitus/terapia , Insuficiência Pancreática Exócrina/etiologia , Insuficiência Pancreática Exócrina/fisiopatologia , Insuficiência Pancreática Exócrina/terapia , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/terapia , Avaliação Nutricional , Apoio Nutricional/tendências , Osteoporose/diagnóstico , Osteoporose/etiologia , Osteoporose/prevenção & controle , Osteoporose/terapia , Neoplasias Pancreáticas/fisiopatologia , Neoplasias Pancreáticas/terapia , Guias de Prática Clínica como Assunto , Lesões Pré-Cancerosas/fisiopatologia , Lesões Pré-Cancerosas/cirurgia , Lesões Pré-Cancerosas/terapia
14.
Cancer Treat Rev ; 58: 77-90, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28704777

RESUMO

Squamous cell carcinoma of the lung arises from preinvasive progenitors in the central airways. The archetypal model appears to be a stepwise morphological progression until there is invasion of the basement membrane. However, not every lesion appears to follow this course and many individuals can have stable disease, or indeed regress to normal epithelium. From our increased understanding of the molecular pathology it is becoming apparent that the respiratory epithelium accumulates progressive genetic and epigenetic insults in response to carcinogens. Still, little is known about how to predict those 'at risk' of progression, and it is likely that in the future molecular signatures will underpin prediction models of developing invasive lung cancer. Currently, autofluorescence bronchoscopy gives us the ability to follow the natural history of these lesions, with the prospect that detecting and treating lesions early may improve survival. However, treatment remains controversial, and radical therapies are offered to individuals with carcinoma in situ who may never develop invasive cancer. This has paved the way for the use of minimally invasive bronchoscopic treatments, which, while apparently effective, have not been tested in randomised controlled trials. In this paper we describe the known biology and natural history of preinvasive lesions and review the current treatment strategies.


Assuntos
Carcinoma in Situ/diagnóstico por imagem , Carcinoma in Situ/terapia , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/patologia , Imagem Óptica , Lesões Pré-Cancerosas/diagnóstico por imagem , Lesões Pré-Cancerosas/terapia , Antineoplásicos/uso terapêutico , Braquiterapia , Broncoscopia/métodos , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/prevenção & controle , Quimioprevenção , Humanos , Neoplasias Pulmonares/prevenção & controle , Invasividade Neoplásica , Estadiamento de Neoplasias , Fotoquimioterapia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/fisiopatologia , Escarro/citologia
15.
Eur J Endocrinol ; 177(1): 93-102, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28432270

RESUMO

BACKGROUND: The presence of virilizing signs associated with high serum androgen levels in postmenopausal women is rare. Virilizing ovarian tumors (VOTs) and ovarian stromal hyperthecosis (OH) are the most common etiologies in virilized postmenopausal women. The differential diagnosis between these two conditions is often difficult. OBJECTIVE: To evaluate the contribution of clinical features, hormonal profiles and radiological studies to the differential diagnosis of VOT and OH. DESIGN: A retrospective study. SETTING: A tertiary center. MAIN OUTCOME MEASURES: Clinical data, hormonal status (T, E2, LH and FSH), pelvic images (transvaginal sonography and MRI) and anatomopathology were reviewed. PATIENTS: Thirty-four postmenopausal women with a diagnosis of VOT (13 women) and OH (21 women) were evaluated retrospectively. RESULTS: Clinical signs of hyperandrogenism were more prevalent in the VOT group than the OH group. Although the VOT group showed higher T and E2 levels and lower gonadotropin levels than the OH group, a great overlap occurred among the hormone levels. A pelvic MRI provided an accurate differentiation of these two conditions. CONCLUSION: In this group of patients, the main features contributing to the differential diagnosis of VOT and OH were serum levels of testosterone and gonadotropins and the presence of an ovarian nodule identified on the MRI. Although the association of clinical, hormonal and radiological features contributes to the differential diagnosis of these two conditions, histopathological analysis remains the gold standard for the diagnosis of ovarian hyperandrogenism in postmenopausal women.


Assuntos
Estradiol/sangue , Hiperandrogenismo/etiologia , Neoplasias Ovarianas/diagnóstico por imagem , Ovário/diagnóstico por imagem , Lesões Pré-Cancerosas/diagnóstico por imagem , Testosterona/sangue , Regulação para Cima , Idoso , Estudos de Coortes , Diagnóstico Diferencial , Regulação para Baixo , Feminino , Hormônio Foliculoestimulante Humano/sangue , Seguimentos , Humanos , Hiperandrogenismo/epidemiologia , Hiperplasia/sangue , Hiperplasia/diagnóstico por imagem , Hiperplasia/patologia , Hiperplasia/fisiopatologia , Hormônio Luteinizante/sangue , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Tamanho do Órgão , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/fisiopatologia , Ovário/patologia , Pós-Menopausa , Lesões Pré-Cancerosas/sangue , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/fisiopatologia , Prevalência , Estudos Retrospectivos , Tecoma (Neoplasia)/sangue , Tecoma (Neoplasia)/diagnóstico por imagem , Tecoma (Neoplasia)/patologia , Tecoma (Neoplasia)/fisiopatologia , Carga Tumoral , Ultrassonografia
16.
Surg Pathol Clin ; 9(4): 705-715, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27926368

RESUMO

Although the pancreas is affected by only a small fraction of known inherited disorders, several of these syndromes predispose patients to pancreatic adenocarcinoma, a cancer that has a consistently dismal prognosis. Still other syndromes are associated with neuroendocrine tumors, benign cysts, or recurrent pancreatitis. Because of the variability of pancreatic manifestations and outcomes, it is important for clinicians to be familiar with several well-described genetic disorders to ensure that patients are followed appropriately. The purpose of this review was to briefly describe the hereditary syndromes that are associated with pancreatic disorders and neoplasia.


Assuntos
Predisposição Genética para Doença/genética , Neoplasias Pancreáticas/genética , Lesões Pré-Cancerosas/genética , Polipose Adenomatosa do Colo/complicações , Síndrome de Beckwith-Wiedemann/complicações , Fibrose Cística/complicações , Displasia Fibrosa Poliostótica/complicações , Genes Supressores de Tumor , Síndrome Hereditária de Câncer de Mama e Ovário/complicações , Humanos , Melanoma/complicações , Neoplasia Endócrina Múltipla Tipo 1/complicações , Síndromes Neoplásicas Hereditárias/complicações , Neurofibromatose 1/complicações , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/fisiopatologia , Pancreatite Crônica/complicações , Síndrome de Peutz-Jeghers/complicações , Lesões Pré-Cancerosas/fisiopatologia , Esclerose Tuberosa/complicações , Doença de von Hippel-Lindau/complicações
17.
Arch Biochem Biophys ; 606: 1-9, 2016 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-27403965

RESUMO

Chrysin (CH) is natural, biologically active compound, belongs to flavoniod family and possesses diverse pharmacological activities as anti-inflammatory, anti-oxidant and anti-cancer. It is found in many plants, honey and propolis. In the present study, we investigated the chemopreventive efficacy of CH against N-nitrosodiethylamine (DEN) initiated and Fe-NTA induced precancerous lesions and its role in regulating oxidative injury, hyperproliferation, tumor incidences, histopathological alterations, inflammation, and apoptosis in the kidneys of Wistar rats. Renal cancer was initiated by single intraperitoneal (i.p.) injection of DEN (200 mg/kg bw) and promoted by twice weekly injection of ferric nitrilotriacetate (Fe-NTA) 9 mg Fe/kg bw for 16 weeks. CH attenuated Fe-NTA enhanced renal lipid peroxidation, serum toxicity markers and restored renal anti oxidant armory significantly. CH supplementation suppressed the development of precancerous lesions via down regulation of cell proliferation marker like PCNA; inflammatory mediators like TNF-α, IL-6, NFkB, COX-2, iNOS; tumor incidences. CH up regulated intrinsic apoptotic pathway proteins like bax, caspase-9 and caspase-3 along with down regulation of Bcl-2 triggering apoptosis. Histopathological and ultra structural alterations further confirmed biochemical and immunohistochemical results. These results provide powerful evidence for the chemopreventive efficacy of CH against chemically induced renal carcinogenesis possibly by modulation of multiple molecular pathways.


Assuntos
Flavonoides/química , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/prevenção & controle , Lesões Pré-Cancerosas/fisiopatologia , Animais , Anticarcinógenos/química , Antioxidantes/química , Apoptose , Carcinogênese , Proliferação de Células , Compostos Férricos , Inflamação , Rim/patologia , Neoplasias Renais/fisiopatologia , Peroxidação de Lipídeos , Masculino , Ácido Nitrilotriacético/análogos & derivados , Estresse Oxidativo , Lesões Pré-Cancerosas/induzido quimicamente , Ratos , Ratos Wistar , Regulação para Cima
18.
Am J Rhinol Allergy ; 30(3): 83-90, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27216341

RESUMO

OBJECTIVES: The goal of this study was to review the main lesion types of the nasal skin and appropriate treatment strategies rather than to present a comprehensive list of all diseases that affect the skin that can involve the nose. METHODS: We reviewed the main nasal skin lesion types and available treatment strategies. Nasal skin lesions were classified as benign, premalignant, or malignant. RESULTS: Benign lesions of the nose include nonmalignant tumoral lesions (i.e., freckles, comedo, adenoma sebaceum [Pringle disease], hydrocystoma, fibrous papules, sebaceous hyperplasia, and rhinophyma), autoimmune and inflammatory conditions (i.e., pemphigus, sarcoidosis, systemic lupus erythematosus, facial eosinophilic granuloma, rosacea, herpes zoster infection, leishmaniasis, and leprosy), and vascular lesions (i.e., telangiectasis, hemangioma, and spider nevus). Premalignant lesions are actinic keratosis and keratoacanthoma; and malignant tumors are melanoma, basal cell carcinoma, and squamous cell carcinoma. Regardless of whether or not they are malignant, all facial lesions can yield significant cosmetic discomfort that should be evaluated carefully before commencing any curative or corrective intervention. In general, benign lesions are treated with dermabrasive modalities, such as trichloroacetic acid, phenol, salicylate, and laser ablation. Electrocautery, cryosurgery, and surgical excision are also used, although these methods may result in scar formation, which can sometimes be more problematic than the original lesion itself. CONCLUSION: Any disease that affects the skin, especially those diseases that are triggered by ultraviolet exposure, can involve the face and nose. Cosmetic defects due both to the lesion itself and the intervention must be discussed with the patient, preferably in the presence of a first-degree relative, before commencement of treatment. As a result of heterogeneity of skin lesions of the nose, appropriate education of general practitioners as well as otorhinolaryngologists is mandatory.


Assuntos
Doenças Autoimunes/terapia , Dermabrasão , Doenças Nasais/terapia , Neoplasias Nasais/terapia , Lesões Pré-Cancerosas/terapia , Dermatopatias/terapia , Doenças Vasculares/terapia , Animais , Doenças Autoimunes/fisiopatologia , Criocirurgia , Eletrocoagulação , Humanos , Doenças Nasais/fisiopatologia , Neoplasias Nasais/fisiopatologia , Lesões Pré-Cancerosas/fisiopatologia , Dermatopatias/fisiopatologia , Doenças Vasculares/fisiopatologia
19.
Eur Respir J ; 47(6): 1829-41, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27076588

RESUMO

The term diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) may be used to describe a clinico-pathological syndrome, as well as an incidental finding on histological examination, although there are obvious differences between these two scenarios. According to the World Health Organization, the definition of DIPNECH is purely histological. However, DIPNECH encompasses symptomatic patients with airway disease, as well as asymptomatic patients with neuroendocrine cell hyperplasia associated with multiple tumourlets/carcinoid tumours. DIPNECH is also considered a pre-neoplastic lesion in the spectrum of pulmonary neuroendocrine tumours, because it is commonly found in patients with peripheral carcinoid tumours.In this review, we summarise clinical, physiological, radiological and histological features of DIPNECH and critically discuss recently proposed diagnostic criteria. In addition, we propose that the term "DIPNECH syndrome" be used to indicate a sufficiently distinct patient subgroup characterised by respiratory symptoms, airflow obstruction, mosaic attenuation with air trapping on chest imaging and constrictive obliterative bronchiolitis, often with nodular proliferation of neuroendocrine cells with/without tumourlets/carcinoid tumours on histology. Surgical lung biopsy is the diagnostic gold standard. However, in the appropriate clinical and radiological setting, transbronchial lung biopsy may also allow a confident diagnosis of DIPNECH syndrome.


Assuntos
Hiperplasia/fisiopatologia , Nódulos Pulmonares Múltiplos/diagnóstico , Nódulos Pulmonares Múltiplos/fisiopatologia , Células Neuroendócrinas/patologia , Biópsia , Tumor Carcinoide/fisiopatologia , Proliferação de Células , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Pulmão/fisiopatologia , Neoplasias Pulmonares/patologia , Lesões Pré-Cancerosas/fisiopatologia , Fibrose Pulmonar/fisiopatologia , Respiração , Síndrome
20.
Proc Natl Acad Sci U S A ; 113(11): 3078-83, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26929329

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an exuberant inflammatory desmoplastic response. The PDAC microenvironment is complex, containing both pro- and antitumorigenic elements, and remains to be fully characterized. Here, we show that sensory neurons, an under-studied cohort of the pancreas tumor stroma, play a significant role in the initiation and progression of the early stages of PDAC. Using a well-established autochthonous model of PDAC (PKC), we show that inflammation and neuronal damage in the peripheral and central nervous system (CNS) occurs as early as the pancreatic intraepithelial neoplasia (PanIN) 2 stage. Also at the PanIN2 stage, pancreas acinar-derived cells frequently invade along sensory neurons into the spinal cord and migrate caudally to the lower thoracic and upper lumbar regions. Sensory neuron ablation by neonatal capsaicin injection prevented perineural invasion (PNI), astrocyte activation, and neuronal damage, suggesting that sensory neurons convey inflammatory signals from Kras-induced pancreatic neoplasia to the CNS. Neuron ablation in PKC mice also significantly delayed PanIN formation and ultimately prolonged survival compared with vehicle-treated controls (median survival, 7.8 vs. 4.5 mo; P = 0.001). These data establish a reciprocal signaling loop between the pancreas and nervous system, including the CNS, that supports inflammation associated with oncogenic Kras-induced neoplasia. Thus, pancreatic sensory neurons comprise an important stromal cell population that supports the initiation and progression of PDAC and may represent a potential target for prevention in high-risk populations.


Assuntos
Capsaicina/uso terapêutico , Carcinoma Ductal Pancreático/prevenção & controle , Denervação , Pâncreas/inervação , Neoplasias Pancreáticas/prevenção & controle , Células Receptoras Sensoriais/fisiologia , Adenocarcinoma in Situ/patologia , Adenocarcinoma in Situ/fisiopatologia , Vias Aferentes , Animais , Animais Recém-Nascidos , Capsaicina/administração & dosagem , Capsaicina/farmacologia , Carcinoma Ductal Pancreático/etiologia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/fisiopatologia , Carcinoma Ductal Pancreático/terapia , Ceruletídeo/toxicidade , Progressão da Doença , Feminino , Gânglios Simpáticos/fisiopatologia , Genes ras , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mielite/complicações , Mielite/genética , Mielite/fisiopatologia , Invasividade Neoplásica , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/fisiopatologia , Neoplasias Pancreáticas/terapia , Pancreatite/induzido quimicamente , Pancreatite/complicações , Pancreatite/fisiopatologia , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/complicações , Lesões Pré-Cancerosas/fisiopatologia , Células Receptoras Sensoriais/efeitos dos fármacos , Medula Espinal/fisiopatologia , Tratos Espinotalâmicos/fisiopatologia , Vértebras Torácicas
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