Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.513
Filtrar
1.
Medicine (Baltimore) ; 100(16): e25607, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33879728

RESUMO

BACKGROUND: Gastric precancerous lesion (GPL) is a necessary stage in the occurrence and development of gastric cancer. At present, the incidence of gastric cancer is increasing year by year. It is important to prevent and control gastric cancer through early detection and intervention. Banxia Xiexin Decoction (BXD) has a good effect in improving symptoms, reducing inflammation, promoting the repair of gastric mucosa, reversing its atrophy and intestinal metaplasia. BXD may be a foreground choice for the treatment of GPL. METHODS: Randomized controlled trials of BXD for GPL will be searched in the relevant database, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), and Chinese Scientific Journal Database (VIP database). The studies of electronic searches will be exported to EndNote V.9.1 software. We will run meta-analyses using the Review Manager (RevMan) V.5.3 software. Any disagreement will be solved in consultation with a third reviewer. RESULTS: Our study aims to explore the efficacy of BXD for GPL and to provide up-to-date evidence for clinical of GPL. CONCLUSION: The conclusion of this study will provide evidence for the efficacy of BXD on GPL. INPLASY REGISTRATION NUMBER: INPLASY 202130102.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Intestinais/tratamento farmacológico , Lesões Pré-Cancerosas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Doença Crônica , Feminino , Gastrite Atrófica/complicações , Gastrite Atrófica/tratamento farmacológico , Humanos , Enteropatias/complicações , Enteropatias/tratamento farmacológico , Neoplasias Intestinais/etiologia , Masculino , Metanálise como Assunto , Lesões Pré-Cancerosas/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Neoplasias Gástricas/etiologia , Revisões Sistemáticas como Assunto , Resultado do Tratamento
2.
Molecules ; 26(7)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33915735

RESUMO

Keratinocyte carcinoma (KC) is a form of skin cancer that develops in keratinocytes, which are the predominant cells present in the epidermis layer of the skin. Keratinocyte carcinoma comprises two sub-types, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This review provides a holistic literature assessment of the origin, diagnosis methods, contributing factors, and current topical treatments of KC. Additionally, it explores the increase in KC cases that occurred globally over the past ten years. One of the principal concepts highlighted in this article is the adverse effects linked to conventional treatment methods of KC and how novel treatment strategies that combine phytochemistry and transdermal drug delivery systems offer an alternative approach for treatment. However, more in vitro and in vivo studies are required to fully assess the efficacy, mechanism of action, and safety profile of these phytochemical based transdermal chemotherapeutics.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Compostos Fitoquímicos/farmacologia , Plantas Medicinais/química , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/metabolismo , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Variação Biológica da População , Estudos Clínicos como Assunto , Gerenciamento Clínico , Suscetibilidade a Doenças , Vias de Administração de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Humanos , Incidência , Queratinócitos/patologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/uso terapêutico , Vigilância da População , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/metabolismo , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico , Resultado do Tratamento
3.
Int J Mol Sci ; 22(6)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33810183

RESUMO

Human papillomavirus (HPV) DNA integration is a crucial event in cervical carcinogenesis. However, scarce studies have focused on studying HPV integration (HPVint) in early-stage cervical lesions. Using HPV capture followed by sequencing, we investigated HPVint in pre-tumor cervical lesions. Employing a novel pipeline, we analyzed reads containing direct evidence of the integration breakpoint. We observed multiple HPV infections in most of the samples (92%) with a median integration rate of 0.06% relative to HPV mapped reads corresponding to two or more sequence breakages. Unlike cancer studies, most integrations events were unique (supported by one read), consistent with the lack of clonal selection. Congruent to other studies, we found that breakpoints could occur, practically, in any part of the viral genome. We noted that L1 had a higher frequency of rupture integration (25%). Based on host genome integration frequencies, we found previously reported integration sites in cancer for genes like FHIT, CSMD1, and LRP1B and putatively many new ones such as those exemplified in CSMD3, ROBO2, and SETD3. Similar host integrations regions and genes were observed in diverse HPV types within many genes and even equivalent integration positions in different samples and HPV types. Interestingly, we noted an enrichment of integrations in most centromeres, suggesting a possible mechanism where HPV exploits this structural machinery to facilitate integration. Supported by previous findings, overall, our analysis provides novel information and insights about HPVint.


Assuntos
Papillomaviridae/fisiologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/etiologia , Integração Viral , Transformação Celular Viral , Biologia Computacional/métodos , Feminino , Genoma Viral , Genótipo , Humanos , México/epidemiologia , Papillomaviridae/classificação , Infecções por Papillomavirus/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/patologia , Análise de Sequência de DNA , Displasia do Colo do Útero/patologia
4.
Cancer Sci ; 111(7): 2546-2557, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32372453

RESUMO

To obtain baseline data for cervical cancer prevention in Japan, we analyzed human papillomavirus (HPV) data from 5045 Japanese women aged less than 40 years and diagnosed with cervical abnormalities at 21 hospitals during 2012-2017. These included cervical intraepithelial neoplasia grade 1 (CIN1, n = 573), CIN2-3 (n = 3219), adenocarcinoma in situ (AIS, n = 123), and invasive cervical cancer (ICC, n = 1130). The Roche Linear Array was used for HPV genotyping. The HPV type-specific relative contributions (RCs) were estimated by adding multiple infections to single types in accordance with proportional weighting attributions. Based on the comparison of type-specific RCs between CIN1 and CIN2-3/AIS/ICC (CIN2+), RC ratios were calculated to estimate type-specific risks for progression to CIN2+. Human papillomavirus DNA was detected in 85.5% of CIN1, 95.7% of CIN2-3/AIS, and 91.2% of ICC. Multiple infections decreased with disease severity: 42.9% in CIN1, 40.4% in CIN2-3/AIS, and 23.7% in ICC (P < .0001). The relative risk for progression to CIN2+ was highest for HPV16 (RC ratio 3.78, 95% confidence interval [CI] 3.01-4.98), followed by HPV31 (2.51, 1.54-5.24), HPV18 (2.43, 1.59-4.32), HPV35 (1.56, 0.43-8.36), HPV33 (1.01, 0.49-3.31), HPV52 (0.99, 0.76-1.33), and HPV58 (0.97, 0.75-1.32). The relative risk of disease progression was 1.87 (95% CI, 1.71-2.05) for HPV16/18/31/33/35/45/52/58, but only 0.17 (95% CI, 0.14-0.22) for HPV39/51/56/59/66/68. Human papillomavirus 16/18/31/33/45/52/58/6/11 included in a 9-valent vaccine contributed to 89.7% (95% CI, 88.7-90.7) of CIN2-3/AIS and 93.8% (95% CI, 92.4-95.3) of ICC. In conclusion, our data support the Japanese guidelines that recommend discriminating HPV16/18/31/33/35/45/52/58 genotypes for CIN management. The 9-valent vaccine is estimated to provide over 90% protection against ICC in young Japanese women.


Assuntos
Genótipo , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/etiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/etiologia , Adolescente , Adulto , Feminino , Humanos , Japão/epidemiologia , Estadiamento de Neoplasias , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/prevenção & controle , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/prevenção & controle , Adulto Jovem
5.
Curr Diab Rep ; 20(6): 19, 2020 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-32277298

RESUMO

PURPOSE OF REVIEW: Fibrocalculous pancreatic diabetes (FCPD) is an uncommon form of diabetes occurring in underprivileged developing countries of the world. We attempt to review the latest evidence on epidemiology, secular trends, etiopathogenic mechanisms, and treatment modalities of FCPD with particular reference to studies from the past decade. RECENT FINDINGS: There has been little new data on FCPD over the past decade even from countries where it was considered to be prevalent. There appears to be a decline in prevalence of the condition of late. There is also some evidence to show that the condition develops due to as yet unknown environmental influences acting on a background of genetic susceptibility. FCPD is a severe form of diabetes and may be a premalignant condition. FCPD deserves more attention than it currently receives, because of its unique clinical features and management strategies, and its propensity to develop pancreatic adenocarcinoma.


Assuntos
Adenocarcinoma/etiologia , Diabetes Mellitus/diagnóstico , Neoplasias Pancreáticas/etiologia , Pancreatite Crônica/diagnóstico , Lesões Pré-Cancerosas/etiologia , Adenocarcinoma/diagnóstico , Calcinose/etiologia , Países em Desenvolvimento , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Diabetes Mellitus/terapia , Fibrose/etiologia , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Neoplasias Pancreáticas/diagnóstico , Pancreatite Crônica/epidemiologia , Pancreatite Crônica/etiologia , Pancreatite Crônica/terapia , Lesões Pré-Cancerosas/diagnóstico , Prevalência , Clima Tropical
6.
Sci Rep ; 10(1): 4899, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32184470

RESUMO

Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC). Methods of identifying BE patients at high risk for progression to high-grade dysplasia (HGD) or EAC are needed to improve outcomes and identify who will benefit most from intensive surveillance or ablative therapy. Clinical predictors of BE progression to HGD or EAC are poorly understood, with multiple contradictory studies. We performed a retrospective study which included 460 patients at Johns Hopkins Hospital who underwent at least 2 upper endoscopies 6 months apart showing biopsy-documented BE between 1992 and 2013. Patients with EAC or HGD at the initial endoscopy were excluded. Demographic, clinicopathological, and endoscopic data were collected. Univariate and multivariate Cox proportional hazards analyses with time to progression to HGD and EAC were performed. Among 460 patients included in the study, 132 BE patients developed HGD and 62 developed EAC. Significant EAC risk factors included age, abdominal obesity, caffeine intake, and the presence of HGD. Risk factors for HGD or EAC included age, caffeine intake, and low-grade dysplasia while colonic adenomas trended towards significance. Notably, a history of statin or SSRI usage reduced the risk of EAC or HGD by 49% or 61%, respectively. Our study validated several known and identified several novel risk factors, including a history of colonic adenomas or caffeine usage. Low-grade dysplasia was a risk factor for progression but various endoscopic characteristics were not, suggesting that screening strategies should focus on histology instead. We identified SSRIs as a new potentially chemoprotective medication.


Assuntos
Adenocarcinoma/etiologia , Esôfago de Barrett/complicações , Neoplasias Esofágicas/etiologia , Lesões Pré-Cancerosas/etiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
7.
PLoS One ; 15(3): e0230220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32163505

RESUMO

Helicobacter pylori is a Gram-negative bacterium that causes chronic atrophic gastritis and peptic ulcers and it has been associated with the development of gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT). One of the more remarkable characteristics of H. pylori is its ability to survive in the hostile environment of the stomach. H. pylori regulates the expression of specific sets of genes allowing it to survive high acidity levels and nutrient scarcity. In the present study, we determined the expression of virulence associated protein D (VapD) of H. pylori inside adenocarcinoma gastric (AGS) cells and in gastric biopsies. Using qRT-PCR, VapD expression was quantified in intracellular H. pylori-AGS cell cultures at different time points and in gastric mucosa biopsies from patients suffering from chronic atrophic gastritis, follicular gastritis, peptic ulcers, gastritis precancerous intestinal metaplasia and adenocarcinoma. Our results show that vapD of H. pylori presented high transcription levels inside AGS cells, which increased up to two-fold above basal values across all assays over time. Inside AGS cells, H. pylori acquired a coccoid form that is metabolically active in expressing VapD as a protection mechanism, thereby maintaining its permanence in a viable non-cultivable state. VapD of H. pylori was expressed in all gastric biopsies, however, higher expression levels (p = 0.029) were observed in gastric antrum biopsies from patients with follicular gastritis. The highest VapD expression levels were found in both antrum and corpus gastric biopsies from older patients (>57 years old). We observed that VapD in H. pylori is a protein that is only produced in response to interactions with eukaryotic cells. Our results suggest that VapD contributes to the persistence of H. pylori inside the gastric epithelial cells, protecting the microorganism from the intracellular environment, reducing its growth rate, enabling long-term infection and treatment resistance.


Assuntos
Proteínas de Bactérias/genética , Gastrite Atrófica/etiologia , Helicobacter pylori/genética , Glicoproteínas de Membrana/genética , Estômago/microbiologia , Estômago/patologia , Adenocarcinoma/etiologia , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Técnicas de Cocultura/métodos , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Gastroscopia/métodos , Infecções por Helicobacter/complicações , Infecções por Helicobacter/patologia , Humanos , Intestinos/microbiologia , Intestinos/patologia , Masculino , Metaplasia/microbiologia , Metaplasia/patologia , Pessoa de Meia-Idade , Úlcera Péptica/metabolismo , Úlcera Péptica/patologia , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Antro Pilórico/microbiologia , Antro Pilórico/patologia , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Virulência/genética , Adulto Jovem
8.
Am J Gastroenterol ; 115(3): 381-387, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899705

RESUMO

OBJECTIVES: The risk of noncardia gastric cancer is increased in the presence of gastric intestinal metaplasia. We aimed to identify demographic and lifestyle factors independently associated with the risk of gastric intestinal metaplasia. METHODS: We used data from a cross-sectional study of patients attending primary care and endoscopy clinics at the Michael E. DeBakey VA Medical Center in Houston, Texas, between February 2008 and August 2013. All patients completed standardized questionnaires and underwent endoscopy with gastric mapping biopsies. Gastric intestinal metaplasia cases included patients with intestinal metaplasia on any noncardia gastric biopsy; we defined extensive gastric intestinal metaplasia as antrum and corpus involvement. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariate logistic regression models. RESULTS: We identified 423 cases with gastric intestinal metaplasia and 1,796 controls without gastric intestinal metaplasia. Older age (vs <60 years: 60-69 years AdjOR, 1.50; 95% CI, 1.17-1.93; ≥70 years AdjOR, 2.12; 95% CI, 1.48-3.04), male sex (AdjOR, 2.76; 95% CI, 1.50-5.10), nonwhite race/ethnicity (vs non-Hispanic white: Hispanic, AdjOR, 2.66; 95% CI, 1.89-3.76; black, AdjOR, 2.36; 95% CI, 1.85-3.02), and current smoking status (AdjOR, 1.78; 95% CI, 1.29-2.48) were independently associated with gastric intestinal metaplasia. These risk factors remained statistically significantly associated with gastric intestinal metaplasia after adjusting for Helicobacter pylori infection, and their effect sizes were larger for associations with extensive gastric intestinal metaplasia compared with focal gastric intestinal metaplasia. DISCUSSION: Older age, male sex, nonwhite race/ethnicity, and current smoking status were the nonendoscopic factors independently associated with gastric intestinal metaplasia in a predominantly nonimmigrant US population.


Assuntos
Demografia , Intestinos/patologia , Estilo de Vida , Lesões Pré-Cancerosas/etiologia , Gastropatias/etiologia , Estômago/patologia , Saúde dos Veteranos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/patologia , Estudos Prospectivos , Fatores de Risco , Gastropatias/diagnóstico , Gastropatias/patologia , Texas
9.
Breast Cancer Res Treat ; 179(2): 511-517, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31701300

RESUMO

PURPOSE: The malignant upgrade rate of flat epithelial atypia (FEA) diagnosed on core needle biopsy varies between 0 and 30%. Excision versus observation with radiological follow-up for these lesions remains controversial. We hypothesize that the local rate of FEA is low and that close radiological surveillance is a reasonable treatment option for patients diagnosed with pure FEA on breast needle core needle biopsy. METHODS: This study was a retrospective review of a prospectively collated provincial pathology database. Patients diagnosed with FEA alone on needle core biopsy between 2006 and 2016 were included in our analysis. Patients who had FEA present together with either in situ or invasive carcinoma within the same biopsy cores were excluded. Along with patient demographics, the size of the lesion on preoperative imaging, the method of extraction, and the presence of co-existing benign and malignant pathology on final excision biopsy were analyzed. An independent pathological review was performed to confirm our results and help reduce inter-observer bias. RESULTS: The local rate of malignant upgrade when pure FEA is diagnosed on a breast needle core biopsy is 12%. Age at time of diagnosis, size of original lesion on mammogram, presence of atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia on core needle biopsy, the use of vacuum-assisted biopsy (VAB), or concordant imaging did not significantly correlate with malignant upgrade risk. None of the patients who were managed with radiological follow-up had malignant upgrade during follow-up. Patients undergoing radiological follow-up alone were more likely to have a VAB, concordant imaging, and no concurrent ADH. CONCLUSION: Our local malignant upgrade rate is consistent with published literature. We suggest radiological follow-up is a safe alternative in patients with pure flat epithelial atypia and concordant imaging, particularly those patients with small lesions in which microcalcifications can be removed completely with vacuum-assisted biopsy.


Assuntos
Mama/patologia , Lesões Pré-Cancerosas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/cirurgia , Carcinoma Intraductal não Infiltrante/diagnóstico , Diagnóstico Diferencial , Progressão da Doença , Feminino , Seguimentos , Humanos , Biópsia Guiada por Imagem , Imuno-Histoquímica , Mamografia , Pessoa de Meia-Idade , Gradação de Tumores , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/cirurgia , Estudos Retrospectivos , Risco
10.
Inflamm Bowel Dis ; 26(2): 167-180, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31372648

RESUMO

BACKGROUND: Patients with longstanding inflammatory bowel disease (IBD; ie, ulcerative colitis and Crohn's disease) have an increased risk of colorectal cancer (CRC). Due to ongoing inflammation, IBD-associated dysplastic lesions can develop. These lesions have an increased risk to progress to cancer compared with sporadic adenomas, which are also found in these patients. Differentiating between these 2 types of dysplasia remains challenging, both clinically and histologically, while treatment strategies may differ. Therefore, the aim of this study was to investigate molecular alterations associated with colorectal dysplasia to cancer progression in IBD and evaluate to what extent these alterations differ from sporadic adenomas. METHODS: DNA copy number aberrations and mutation analyses of 48 genes were performed by next-generation sequencing in 43 IBD-associated dysplastic lesions, 30 of which were dysplastic and 13 of which were cancers. Results were compared with existing DNA copy number and mutation data from 118 sporadic adenomas and 24 sporadic cancers. RESULTS: Inflammatory bowel disease-associated dysplastic lesions harbor patterns of DNA copy number aberrations comparable to carcinomas, which are rare in sporadic adenomas. TP53 mutation was the most frequent mutation observed in IBD-associated dysplastic lesions and in cancers. FBXW7 was mutated significantly more often in IBD-associated dysplastic lesions than in sporadic adenomas. CONCLUSIONS: Inflammatory bowel disease-associated dysplastic lesions show more DNA copy number aberrations than sporadic adenomas. TP53 and FBXW7 mutations appear to be involved in the development of IBD-associated dysplastic lesions and cancer. These findings indicate that IBD-associated dysplastic lesions are more genomically unstable, possibly reflecting a faster progression toward cancer.


Assuntos
Adenoma/genética , Instabilidade Cromossômica , Colite Ulcerativa/patologia , Neoplasias Colorretais/genética , Doença de Crohn/patologia , Lesões Pré-Cancerosas/genética , Adenoma/etiologia , Adolescente , Adulto , Transformação Celular Neoplásica , Colite Ulcerativa/complicações , Neoplasias Colorretais/etiologia , Doença de Crohn/complicações , Análise Mutacional de DNA , Progressão da Doença , Feminino , Humanos , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/etiologia , Adulto Jovem
11.
Int J Cancer ; 146(9): 2413-2422, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31291470

RESUMO

In this registry-based cohort study, we estimated the risk of human papillomavirus (HPV)-related anogenital premalignancies and cancer in renal transplant recipients (RTRs) compared to a nontransplanted comparison cohort. We identified all first-time RTRs in Denmark during 1990-2015 in a nationwide nephrology register. For each RTR, we randomly selected 50 age- and sex-matched non-RTRs from the background population. The study population was followed for diagnoses of cervical, vaginal, vulvar, penile and anal intraepithelial neoplasia grades 2-3 (IN2/3) and cancer for up to 27 years. We estimated hazard ratios (HRs) of anogenital IN2/3 and cancer in RTRs vs. non-RTRs by Cox regression separately for men and women using age as underlying timescale, adjusting for income, education, HPV vaccination and immunocompromising conditions. We included 4,261 RTRs and 213,673 non-RTRs. RTRs had increased hazard of cervical (HR = 2.1, 95% CI: 1.7-2.8), vaginal (HR = 35.0, 95% CI: 13.9-87.7), vulvar (HR = 16.4, 95% CI: 10.4-25.8), penile (HR = 21.9, 95% CI: 11.1-43.5) and anal (women: HR = 51.1, 95% CI: 28.0-93.1; men: HR = 39.0, 95% CI: 16.7-91.1) IN2/3. The HRs of anogenital cancers were also increased at most sites. The HR of anogenital IN2/3 in female RTRs tended to be higher during graft function than during dialysis. In female RTRs aged <40 years at transplantation, 10-15% had cervical IN2/3 and 5-12% had vaginal/vulvar/anal IN2/3 within 20 years after transplantation, compared to 4-8 and 0.2-0.4%, respectively, of female non-RTRs. In conclusion, RTRs had substantially higher risk of HPV-related anogenital premalignancies and cancer than non-RTRs.


Assuntos
Neoplasias do Ânus/etiologia , Transplante de Rim/efeitos adversos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Lesões Pré-Cancerosas/etiologia , Transplantados/estatística & dados numéricos , Neoplasias Urogenitais/etiologia , Adulto , Neoplasias do Ânus/patologia , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/patologia , Prognóstico , Sistema de Registros , Neoplasias Urogenitais/patologia
12.
Indian J Med Microbiol ; 37(2): 255-262, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31745028

RESUMO

Background: Identification of 14 high-risk human papillomavirus (HR-HPV) is immensely important in elucidating molecular epidemiology, patient monitoring and evidence-based treatment. There is paucity of such data from Chhattisgarh state of Central India. The present study has evaluated tagging oligonucleotide cleavage and extension-mediated Anyplex HR-HPV genotyping assay in identification of 14 HR-HPV genotypes attributable to premalignant and malignant cervical lesion in comparison to GP5+/6+ assay, cytology and colposcopy. Materials and Methods: A total of 185 clinically suspected cases of premalignant and malignant cervical lesion were investigated by HR-HPV genotyping, GP5+/6+, cytology and colposcopy. Results: Genotyping assay showed clinical sensitivity and specificity of 86.5% (confidence interval [CI]: 80.7-91.0) and 100% (CI: 86.3-100) respectively and found noninferior to GP5+/6+ assay (P > 0.05). HR-HPV prevalence was 76.3%, 88.4%, 94.8%, 100% and 100% among cervical intraepithelial neoplasia (CIN) Grade I-III, squamous cell carcinoma and adenocarcinoma cases, respectively. The four most common genotypes detected in CIN I-III were HPV 16 (63.9%), HPV 39 (15.0%), HPV 18 (6.0%) and HPV 33 (5.3%). In cervical cancer (CC) cases, HPV 16 (44.4%), HPV 39 (11.1%), dual infection of HPV 16, 18 (11.1%) and triple infection of HPV 16, 18, 33 (11.1%) were the four most identified genotypic aetiologies. A novel coinfection of HR-HPV 35, 39 were found in two and one cases of CIN I and II. Finding of HPV 39 as the second most prevalent genotype was unusual and underscores the importance of genotyping screening. Conclusion: Anyplex HR-HPV assay is arguably the useful assay for better patient management and can be useful for HR-HPV screening by its unique individual genotype identification of all HR-HPV. Finding of HPV 16, 39, 18, 33 and coinfection of 16,18 and 16, 18, 33 in CIN and CC would help vaccine manufacturer to design specific future HPV polyvalent vaccine preparation to curb down the CC-associated mortality.


Assuntos
Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Lesões Pré-Cancerosas/etiologia , Neoplasias do Colo do Útero/etiologia , Adulto , Fatores Etários , Idoso , Colposcopia , Citodiagnóstico , Detecção Precoce de Câncer , Feminino , Genótipo , Papillomavirus Humano 16/classificação , Papillomavirus Humano 16/genética , Humanos , Pessoa de Meia-Idade , Tipagem Molecular , Infecções por Papillomavirus/epidemiologia , Lesões Pré-Cancerosas/diagnóstico , Gravidez , Prevalência , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Adulto Jovem
13.
AIDS Patient Care STDS ; 33(11): 459-465, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31682165

RESUMO

The natural history of squamous intraepithelial lesions (SILs) in the anal canal of HIV-infected men is incompletely understood. We assessed the incidence and factors associated with SIL and invasive anal squamous cell carcinoma (IASCC) among HIV-infected men with normal cytology at baseline. We performed a single-center prospective cohort study [men who have sex with men (MSM) and men who have sex with women (MSW)]. The incidence of anal canal SIL (low grade and high grade) and IASCC were estimated and predictive factors analyzed. The study population comprised 297 HIV-infected men with a normal cytology result and no anal human papillomavirus (HPV)-related diseases. Of these, 251 (85%) had at least one evaluable set of cytology data during follow-up (172 MSM, 79 MSW). The median follow-up time was 4 years. The cumulative incidence of SIL was 43% (107/251): 52% in MSM (90/172) and 22% in MSW (17/79), p < 0.0001. The incidence rate of SILs was 109 (95% confidence interval = 90-132) per 1000 person-years: 142 in MSM and 49 in MSW, p < 0.0001. HPV infection, receiving antiretroviral treatment (ART), and being MSM were independently associated risk factors. The incidence of IASCC was 0.15 per 1000 person-years among MSM and 0 in MSW. HIV-infected men, both MSM and MSW, are at high risk of developing SIL despite having a normal anal cytology at baseline. The incidence of anal canal SIL was higher among MSM, but was also remarkable among MSW. Independent risk factors associated with SIL were being HIV-infected MSM at high risk for acquisition of STIs, time on ART, and HPV infection.


Assuntos
Canal Anal/patologia , Neoplasias do Ânus/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Heterossexualidade , Homossexualidade Masculina , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Lesões Pré-Cancerosas/etiologia , Lesões Intraepiteliais Escamosas/epidemiologia , Adulto , Terapia Antirretroviral de Alta Atividade , Doenças do Ânus/epidemiologia , Neoplasias do Ânus/patologia , Neoplasias do Ânus/virologia , Citodiagnóstico , Feminino , Infecções por HIV/virologia , Soropositividade para HIV , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/etiologia , Infecções por Papillomavirus/patologia , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/virologia , Prevalência , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia , Lesões Intraepiteliais Escamosas/patologia , Lesões Intraepiteliais Escamosas/virologia
14.
Front Immunol ; 10: 2385, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31649683

RESUMO

Vaccines can successfully prevent viral infections and have emerged as an effective strategy for preventing some virally mediated malignancies. They also represent our major hope for cost-effective reduction of the cancer burden. The concept that the immune system mediates surveillance and editing roles against tumors is now well-established in murine models. However, harnessing the immune system to prevent human cancers that do not have a known viral etiology has not yet been realized. Most human cancers originate in a premalignant phase that is more common than the cancer itself. Many of the genetic changes that underlie carcinogenesis originate at this stage when the malignant phenotype is not manifest. Studies evaluating host response in human premalignancy have documented that these lesions are immunogenic, setting the stage for immune-based approaches for targeted prevention of human cancer. However, recent studies suggest that the hierarchy of T cell exhaustion and immune-suppressive factors have already begun to emerge in many preneoplastic states. These considerations underscore the need to link immune prevention to earlier detection of such lesions and to personalize such approaches based on the status of the pre-existing immune response.


Assuntos
Vacinas Anticâncer , Neoplasias/etiologia , Neoplasias/prevenção & controle , Viroses/complicações , Animais , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/imunologia , Transformação Celular Viral , Doença Crônica , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Suscetibilidade a Doenças , Detecção Precoce de Câncer , Humanos , Vigilância Imunológica , Imunoterapia , Mutação , Neoplasias/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/prevenção & controle , Linfócitos T/imunologia , Linfócitos T/metabolismo , Resultado do Tratamento , Viroses/virologia
15.
World J Gastroenterol ; 25(31): 4343-4359, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31496617

RESUMO

the bile duct system and pancreas show many similarities due to their anatomical proximity and common embryological origin. Consequently, preneoplastic and neoplastic lesions of the bile duct and pancreas share analogies in terms of molecular, histological and pathophysiological features. Intraepithelial neoplasms are reported in biliary tract, as biliary intraepithelial neoplasm (BilIN), and in pancreas, as pancreatic intraepithelial neoplasm (PanIN). Both can evolve to invasive carcinomas, respectively cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary neoplasms arise in biliary tract and pancreas. Intraductal papillary neoplasm of the biliary tract (IPNB) share common histologic and phenotypic features such as pancreatobiliary, gastric, intestinal and oncocytic types, and biological behavior with the pancreatic counterpart, the intraductal papillary mucinous neoplasm of the pancreas (IPMN). All these neoplastic lesions exhibit similar immunohistochemical phenotypes, suggesting a common carcinogenic process. Indeed, CCA and PDAC display similar clinic-pathological features as growth pattern, poor response to conventional chemotherapy and radiotherapy and, as a consequence, an unfavorable prognosis. The objective of this review is to discuss similarities and differences between the neoplastic lesions of the pancreas and biliary tract with potential implications on a common origin from similar stem/progenitor cells.


Assuntos
Neoplasias dos Ductos Biliares/etiologia , Carcinoma in Situ/etiologia , Carcinoma Ductal Pancreático/etiologia , Colangiocarcinoma/etiologia , Neoplasias Pancreáticas/etiologia , Lesões Pré-Cancerosas/etiologia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/terapia , Sistema Biliar/patologia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Carcinogênese/patologia , Carcinoma in Situ/patologia , Carcinoma in Situ/terapia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/terapia , Colangiocarcinoma/patologia , Colangiocarcinoma/terapia , Progressão da Doença , Humanos , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/terapia , Células-Tronco/patologia
16.
Nutrition ; 67-68: 110556, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31554603

RESUMO

OBJECTIVES: Obesity is a risk factor for malignancy in various tissues, and has been associated with gut microbiota alterations. However, the link between obesity-associated microbiota and gastric pathogenesis has not been clarified. We demonstrated that high-fat-diet (HFD) feeding causes intestinal metaplasia, which are precancerous lesions of the stomach, with augmented gastric leptin signaling. The aim of this study was to investigate the precise role of leptin signaling in the altered microbiota composition and pathogenesis in the stomach during diet-induced obesity. METHODS: Male C57 BL/6 J, leptin receptor (Lepr)-mutated db/db, and gastrointestinal epithelium-specific Lepr conditional knockout (T3 b-Lepr cKO) mice were fed a HFD or control diet. Gastrointestinal microbiota was analyzed by 16 S rRNA gene sequences and quantitative polymerase chain reaction. Transplantation of gastric microbiota of HFD-fed mice was performed to evaluate metaplasia onset in recipient mice. RESULTS: One week of HFD caused severe microbial dysbiosis in the stomach. The microbiota changes were accompanied by increased gastric leptin, leading to the consequent development of intestinal metaplasia. Transplantation of gastric microbiota from HFD-fed mice induced intestinal metaplasia in recipient mice; however, only a limited effect on pathogenesis was noted. HFD-fed db/db mice did not show a decrease in microbial abundance. Moreover, T3 b-Lepr cKO mice failed spontaneous obesity, and suppressed decreased abundance of gastric microbiota and occurrence of intestinal metaplasia during HFD feeding similar to db/db mice. CONCLUSIONS: Gastric leptin signaling modulates the gastric microbiota community and regulates the pathogenesis in the gastric mucosa.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/fisiologia , Leptina/metabolismo , Lesões Pré-Cancerosas/etiologia , Receptores para Leptina/metabolismo , Neoplasias Gástricas/etiologia , Animais , Disbiose/etiologia , Disbiose/metabolismo , Disbiose/microbiologia , Transplante de Microbiota Fecal , Microbioma Gastrointestinal/genética , Masculino , Metaplasia/etiologia , Metaplasia/metabolismo , Metaplasia/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Mutantes , Mutação , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/microbiologia , Receptores para Leptina/deficiência , Receptores para Leptina/genética , Transdução de Sinais , Estômago/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/microbiologia
17.
Rev Med Interne ; 40(11): 729-732, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31400822

RESUMO

Numerous systemic diseases (vasculitis, connective tissue disease or sarcoidosis) can display an involvement of the perianal skin, the rectum and/or the anus. Such knowledge is important in order to treat these complications specifically when possible. Lesions of the anorectum arising from systemic diseases can sometimes cause perforations in the peritoneal cavity (if concerning the higher portion of the rectum) and/or fistulization to the anal margin. Differential diagnosis, mostly infectious or inflammatory (Crohn's disease) must be ruled out in every case. Other systemic diseases can display specific manifestations as this is the case in scleroderma which can lead to anal incontinence. Despite the relative rarity of these manifestations, their ignorance would forbid global management of these complex diseases. It should thus be detected in each consultation and a regular follow-up must be provided with a proctologist and/or a gastroenterologist when needed.


Assuntos
Neoplasias do Ânus/etiologia , Doenças do Tecido Conjuntivo/complicações , Incontinência Fecal/etiologia , Lesões Pré-Cancerosas/etiologia , Sarcoidose/complicações , Vasculite/complicações , Humanos
18.
World J Gastroenterol ; 25(30): 4105-4124, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31435167

RESUMO

Gastric cancer remains the third leading cause of mortality from cancer worldwide and carries a poor prognosis, due largely to late diagnosis. The importance of the interaction between Helicobacter pylori (H. pylori) infection, the main risk factor, and host-related genetic factors has been studied intensively in recent years. The genetic predisposition for non-hereditary gastric cancer is difficult to assess, as neither the real prevalence of premalignant gastric lesions in various populations nor the environmental risk factors for cancer progression are clearly defined. For non-cardiac intestinal-type cancer, identifying the factors that modulate the progression from inflammation toward cancer is crucial in order to develop preventive strategies. The role of cytokines and their gene variants has been questioned in regard to non-self-limiting H. pylori gastritis and its evolution to gastric atrophy and intestinal metaplasia; the literature now includes various and non-conclusive results on this topic. The influence of the majority of cytokine single nucleotide polymorphisms has been investigated for gastric cancer but not for preneoplastic gastric lesions. Among the investigated gene variants onlyIL10T-819C, IL-8-251, IL-18RAP917997, IL-22 rs1179251, IL1-B-511, IL1-B-3954, IL4R-398 and IL1RN were identified as predictors for premalignant gastric lesions risk. One of the most important limiting factors is the inhomogeneity of the studies (e.g., the lack of data on concomitant H. pylori infection, methods used to assess preneoplastic lesions, and source population). Testing the modifying effect of H. pylori infection upon the relationship between cytokine gene variants and premalignant gastric lesions, or even testing the interaction between H. pylori and cytokine gene variants in multivariable models adjusted for potential covariates, could increase generalizability of results.


Assuntos
Citocinas/genética , Mucosa Gástrica/patologia , Infecções por Helicobacter/epidemiologia , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/patologia , Atrofia/epidemiologia , Atrofia/etiologia , Atrofia/patologia , Fatores de Confusão Epidemiológicos , Progressão da Doença , Mucosa Gástrica/microbiologia , Predisposição Genética para Doença , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Humanos , Metaplasia/epidemiologia , Metaplasia/etiologia , Metaplasia/patologia , Polimorfismo de Nucleotídeo Único , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/etiologia , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia
19.
PLoS One ; 14(8): e0221024, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31425520

RESUMO

Cholangiocarcinoma (CCA) is a primary malignant tumor of the epithelial lining of biliary track associated with endemic Opisthorchis viverrini (Ov) infection in northeastern Thailand. Ov-associated periductal fibrosis (PDF) is the precancerous lesion for CCA, and can be detected by ultrasonography (US) to facilitate early detection. However, US cannot be used to distinguish PDF from cancer. Therefore, the objective of this study was to discover and qualify potential urine biomarkers for CCA detection in at-risk population. Biomarker discovery was conducted on pooled urine samples, 42 patients per group, with PDF or normal bile duct confirmed by ultrasound. After depletion of high abundance proteins, 338 urinary proteins were identified from the 3 samples (normal-US, PDF-US, CCA). Based on fold change and literature review, 70 candidate proteins were selected for qualification by multiple reaction monitoring mass spectrometry (MRM-MS) in 90 individual urine samples, 30 per group. An orthogonal signal correction projection to latent structures discriminant analysis (O-PLS-DA) multivariate model constructed from the 70 candidate biomarkers significantly discriminated CCA from normal and PDF groups (P = 0.003). As an independent validation, the expression of 3 candidate proteins was confirmed by immunohistochemistry in CCA tissues: Lysosome associated membrane glycoprotein 1 (LAMP1), lysosome associated membrane glycoprotein 2 (LAMP2) and cadherin-related family member 2 (CDHR2). Further evaluation of these candidate biomarkers in a larger cohort is needed to support their applicability in a clinical setting for screening and monitoring early CCA and for CCA surveillance.


Assuntos
Neoplasias dos Ductos Biliares/diagnóstico , Ductos Biliares/patologia , Biomarcadores Tumorais/urina , Colangiocarcinoma/diagnóstico , Opistorquíase/complicações , Lesões Pré-Cancerosas/diagnóstico , Adulto , Idoso , Animais , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/urina , Colangiocarcinoma/patologia , Colangiocarcinoma/urina , Diagnóstico Diferencial , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/urina , Proteômica/métodos , Espectrometria de Massas em Tandem/métodos , Tailândia , Ultrassonografia
20.
Am J Surg Pathol ; 43(11): 1547-1553, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31368913

RESUMO

Condyloma acuminatum rarely occurs in the urinary bladder and is considered to be a risk factor for squamous cell carcinoma, although there are only a few publications with limited cases. We studied 51 cases of condyloma acuminatum of the urinary bladder from transurethral resections of the urinary bladder of 38 patients from the consult files of one of the authors. Transurethral resections of the urinary bladder were obtained from 25 males with a median age of 73 years (range: 41 to 87 y) and 13 females with a median age of 68 years (range: 30 to 86 y). The follow-up period ranged from 15 months to 20 years (median: 6 y). Bladder lesions were accompanied by urethral lesions in 4 men. Eight patients (8/38; 21.0%) had a history of immunosuppression. Seven patients (7/8; 87.5%) from this group had multiple and/or recurrent condylomas. One patient (1/38; 2.6%) with renal transplantation had 10 separate bladder condylomas over time. One patient (1/38; 2.6%) had extensive anogenital condylomas and anal intraepithelial neoplasia grade 3. One patient (1/8; 12.5%) with renal transplantation presented with a solitary condyloma with synchronous squamous cell carcinoma in situ. Three female patients (3/38; 7.9%) had a history of premalignant vagina/cervix lesions. In total, 17 patients (17/38; 44.7%) had squamous cell carcinoma of the bladder, either invasive or in situ. In all cases, the squamous cell carcinoma (either in situ or invasive) was diagnosed either concurrent with the diagnosis of bladder condyloma or within 1 year of the condyloma diagnosis). In total, 9 of 38 (23.7%) patients had invasive squamous cell carcinoma with or without in situ squamous cell carcinoma. Eight of 38 (21.0%) patients had squamous cell carcinoma in situ only (without a definitive invasive component-in 3 cases invasive squamous cell carcinoma could not be excluded with certainty). In total, 19 patients (19/38; 50%) were positive for either low-risk human papillomavirus (LR-HPV) or high-risk human papillomavirus (HR-HPV) or both (3 were positive for both LR-HPV and HR-HPV, 12 patients for only LR-HPV, and 4 for only HR-HPV). Of the 19 patients that were negative for both LR-HPV and HR-HPV, 9 of 19 (47.4%) patients had associated squamous cell carcinoma. Of the 12 patients with only LR-HPV, 4 (33.3%) had associated squamous cell carcinoma (either invasive or in situ). Of the 7 patients with HR-HPV (with or without LR-HPV), 4 (57.1%) has associated squamous cell carcinoma. In summary, condyloma acuminatum of the urinary bladder shows a strong association with squamous cell carcinoma of the bladder, regardless of the condyloma's HPV in situ hybridization results. Immunosuppression is associated with condylomas of the bladder. It is important to distinguish bladder condylomas from papillary urothelial carcinoma, given their different risks for panurothelial disease and risk of squamous cell carcinoma. Recognition of bladder condylomas histologically is often challenging given their rarity, and that they can be negative for both LR-HPV and HR-HPV. The lack of a history of other anogenital human papillomavirus-related lesions further increases the difficulty in establishing the correct diagnosis.


Assuntos
Carcinoma de Células Escamosas/patologia , Condiloma Acuminado/patologia , Lesões Pré-Cancerosas/patologia , Doenças da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/etiologia , Condiloma Acuminado/diagnóstico , Condiloma Acuminado/etiologia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/etiologia , Fatores de Risco , Doenças da Bexiga Urinária/diagnóstico , Doenças da Bexiga Urinária/etiologia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/etiologia , Neoplasias da Bexiga Urinária/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...