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1.
Croat Med J ; 61(4): 319-325, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32881429

RESUMO

AIM: To assess the relationship between Helicobacter pylori (H. pylori) infection and atrophic gastritis (AG) and intestinal metaplasia (IM) development and to assess the rate of dysplasia or gastric cancer development in patients with AG and/or IM. METHODS: This retrospective endoscopic follow-up study enrolled 2214 patients. The patients were followed for at least five years between 2007 and 2017 at the Department of Endoscopy at Antalya Ataturk Government Hospital. The results of third-year and five-year surveillance biopsy were assessed. RESULTS: The mean follow-up time was 7.77 ± 2.78 years. H. pylori was histologically assessed in 1417 (64.6%) patients. Of 198 patients with severe H. pylori infection, 32 (16%) and 139 (70.3%) developed extensive AG and extensive IM, respectively. There was a significant relationship between H. pylori density and AG and IM degrees. High grade dysplasia, early gastric cancer, and advanced gastric cancer were diagnosed in 73 patients with median age 58.2 (28-80) years, and the incidence rate was 3.29% (73/2214). The annual incidence of gastric neoplastic lesions was 0.46% in total, 0.08% for early GC, and 0.02% for advanced gastric cancer. CONCLUSIONS: H. pylori infection has an important role in the development of AG and IM. H. pylori density is directly related to atrophy and metaplasia degree.


Assuntos
Gastrite Atrófica/epidemiologia , Infecções por Helicobacter/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Endoscopia Gastrointestinal , Feminino , Seguimentos , Mucosa Gástrica/patologia , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori , Humanos , Incidência , Masculino , Metaplasia/patologia , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Turquia/epidemiologia
2.
Nat Commun ; 11(1): 4516, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908137

RESUMO

Acinar metaplasia is an initial step in a series of events that can lead to pancreatic cancer. Here we perform single-cell RNA-sequencing of mouse pancreas during the progression from preinvasive stages to tumor formation. Using a reporter gene, we identify metaplastic cells that originated from acinar cells and express two transcription factors, Onecut2 and Foxq1. Further analyses of metaplastic acinar cell heterogeneity define six acinar metaplastic cell types and states, including stomach-specific cell types. Localization of metaplastic cell types and mixture of different metaplastic cell types in the same pre-malignant lesion is shown. Finally, single-cell transcriptome analyses of tumor-associated stromal, immune, endothelial and fibroblast cells identify signals that may support tumor development, as well as the recruitment and education of immune cells. Our findings are consistent with the early, premalignant formation of an immunosuppressive environment mediated by interactions between acinar metaplastic cells and other cells in the microenvironment.


Assuntos
Células Acinares/patologia , Carcinoma Ductal Pancreático/genética , Regulação Neoplásica da Expressão Gênica , Pâncreas/patologia , Neoplasias Pancreáticas/genética , Lesões Pré-Cancerosas/genética , Animais , Animais Geneticamente Modificados , Biópsia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Diferenciação Celular , Modelos Animais de Doenças , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Heterogeneidade Genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Estimativa de Kaplan-Meier , Masculino , Metaplasia/genética , Camundongos , Mutação , Pâncreas/citologia , Pâncreas/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Lesões Pré-Cancerosas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , RNA-Seq , Análise de Célula Única , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Microambiente Tumoral/genética
3.
Nat Commun ; 11(1): 4875, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978388

RESUMO

Single-cell whole-exome sequencing (scWES) is a powerful approach for deciphering intratumor heterogeneity and identifying cancer drivers. So far, however, simultaneous analysis of single nucleotide variants (SNVs) and copy number variations (CNVs) of a single cell has been challenging. By analyzing SNVs and CNVs simultaneously in bulk and single cells of premalignant tissues and tumors from mouse and human BRCA1-associated breast cancers, we discover an evolution process through which the tumors initiate from cells with SNVs affecting driver genes in the premalignant stage and malignantly progress later via CNVs acquired in chromosome regions with cancer driver genes. These events occur randomly and hit many putative cancer drivers besides p53 to generate unique genetic and pathological features for each tumor. Upon this, we finally identify a tumor metastasis suppressor Plekha5, whose deficiency promotes cancer metastasis to the liver and/or lung.


Assuntos
Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Predisposição Genética para Doença/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lesões Pré-Cancerosas/genética , Animais , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Variações do Número de Cópias de DNA , Modelos Animais de Doenças , Heterogeneidade Genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Fígado/patologia , Pulmão/patologia , Camundongos , Camundongos Knockout , Mutação , Lesões Pré-Cancerosas/patologia , Transcriptoma
4.
Am J Gastroenterol ; 115(7): 1036-1044, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32618654

RESUMO

INTRODUCTION: Data on the associations between esophageal histological lesions and risk of esophageal squamous cell carcinoma (ESCC) in general populations are limited. We aimed to investigate these associations in a large Chinese general population to inform future Chinese ESCC screening guidelines. METHODS: We performed endoscopic screening of 21,111 participants aged 40-69 years from 3 high-risk areas of China in 2005-2009, and followed the cohort through 2016. Cumulative incidence and mortality rates of ESCC were calculated by baseline histological diagnosis, and hazard ratios of ESCC, overall and by age and sex, were assessed using the Cox proportional hazards models. RESULTS: We identified 143 new ESCC cases (0.68%) and 62 ESCC deaths (0.29%) during a median follow-up of 8.5 years. Increasing grades of squamous dysplasia were associated with the increasing risk of ESCC incidence and mortality. The cumulative ESCC incidence rates for severe dysplasia/carcinoma in situ, moderate dysplasia (MD), and mild dysplasia were 15.5%, 4.5%, and 1.4%, respectively. Older individuals (50-69 years) had 3.1 times higher ESCC incidence than younger individuals (40-49 years), and men had 2.4 times higher ESCC incidence than women. DISCUSSION: This study confirmed that increasing grades of squamous dysplasia are associated with increasing risk of ESCC and that severe dysplasia and carcinoma in situ require clinical treatment. This study suggests that in high-risk areas of China, patients with endoscopically worrisome MD should also receive therapy, the first screening can be postponed to 50 years, and endoscopic surveillance intervals for unremarkable MD and mild dysplasia can be lengthened to 3 and 5 years, respectively.


Assuntos
Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/patologia , Adulto , Idoso , Biópsia , China/epidemiologia , Esofagoscopia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Risco , Inquéritos e Questionários
5.
PLoS One ; 15(7): e0235906, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697782

RESUMO

BACKGROUND: Esophageal cancer is a deadly cancer with 5-year survival <20%. Although multiple risk factors for esophageal adenocarcinoma (EAC) including obesity, GERD and smoking have been identified, these risk factors do not fully explain the rising incidence of EAC. In this study, we evaluated the association between prior history of tonsillectomy and EAC. Our goal was to determine whether tonsillectomies were more frequent in patients with EAC (cases) than in our thoracic surgery controls. METHODS: Cases included 452 esophagectomy cases, including 396 with EAC and 56 who underwent esophagectomy for Barrett's esophagus (BE) with high grade dysplasia (HGD). 1,102 thoracic surgery patients with surgical indications other than dysplastic BE or esophageal cancer represented the controls for our analysis. The association of tonsillectomy and HGD/EAC were primarily evaluated by using univariate tests and then verified by logistic regression analysis. Baseline demographics, medical history, and thoracic surgery controls were compared by using χ2 tests or 95% CIs. Significant risk factors were considered as covariates in the multivariate models while evaluating the association between tonsillectomy and HGD/EAC. P-values or odds ratios were estimated with 95% confidence limits to identify significances which was more appropriate. RESULTS: Tonsillectomy was more common in cases than controls and was found to have a significant association with esophageal cancer (19.9% vs. 12.7%; p-value = 0.0003). This significant association persisted after controlling for other known risk factors/covariates. CONCLUSION: A prior history of tonsillectomy was significantly associated with HGD/EAC and may represent an independent risk factor for the development of EAC. However, the underlying biology driving this association remains unclear.


Assuntos
Adenocarcinoma/etiologia , Neoplasias Esofágicas/etiologia , Tonsilectomia/efeitos adversos , Adenocarcinoma/diagnóstico , Idoso , Esôfago de Barrett/patologia , Esôfago de Barrett/cirurgia , Estudos de Casos e Controles , Neoplasias Esofágicas/diagnóstico , Esofagectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Lesões Pré-Cancerosas/patologia , Estudos Retrospectivos , Fatores de Risco
6.
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
7.
Am J Clin Pathol ; 154(3): 381-386, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32405650

RESUMO

OBJECTIVES: The 2014 Bethesda System (TBS 2014) guidelines for reporting cervical cytology revised the age for reporting benign endometrial cells (BECs) from 40 years or older to age 45 years or older. We evaluated this change and further investigated if extending the reporting age to 50 years or older may be acceptable. METHODS: We reviewed cases with BECs reported on Papanicolaou tests in women age 40 years or older and 45 years or older before and after implementation of TBS 2014. Follow-up endometrial biopsy/curettage results were categorized as benign, endometrial hyperplasia with or without atypia, or malignant. Hyperplasia and malignant follow-up were considered clinically significant. Clinical data were documented. Results were compared for women age 40 to 44, 45 to 49, and 50 years or older. RESULTS: Follow-up in 15 (100%) women age 40 to 44 years was benign. In women age 45 to 49 years, 61 (96.8%) had benign follow-up, one (1.6%) had atypical hyperplasia, and one (1.6%) had malignant follow-up. In women age 50 years or older, 57 (86.5%) had benign follow-up, four (6%) had malignant follow-up, and seven (7.5%) had atypical or nonatypical hyperplasia. There was a significant difference in follow-up between the age groups of 40 to 49 and 50 or older (P = .023). CONCLUSIONS: We conclude that the TBS 2014 revision was justified. Our data suggest that age 50 years or older rather than age 45 years or older may be an acceptable cutoff for reporting BECs.


Assuntos
Colo do Útero/patologia , Hiperplasia Endometrial/patologia , Endométrio/patologia , Lesões Pré-Cancerosas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Teste de Papanicolaou/métodos , Esfregaço Vaginal/métodos
8.
Clin Imaging ; 66: 7-9, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32442858

RESUMO

PURPOSE: The aim of our study is to evaluate the diagnostic performance of CT-guided biopsy of lung nodules ≤10 mm based on their lobar and segmental location. MATERIALS AND METHODS: This was a retrospective study performed on 193 CT-guided percutaneous transthoracic needle biopsies of lung nodules ≤10 mm in greatest dimension, between January 1, 2013 and April 30, 2019. Biopsies were classified as either diagnostic or non-diagnostic based on final cytology and surgical pathology reports. Diagnostic results were those that met parameters for malignancy or a specific benign diagnosis, whereas atypical cells, non-specific benignity, or insufficient specimen were considered non-diagnostic. RESULTS: A total of 1577 CT-guided percutaneous transthoracic needle biopsies were reviewed. Of these, 193 nodules (12.24%) measured ≤10 mm and were selected for further analysis. Of the 193 biopsies, 138 yielded diagnostic results while 56 yielded nondiagnostic results (71% vs 29%, respectively). When analyzed by nodule location, the superior segments of the lower lobes boasted the highest diagnostic yield compared to nodules located in the basal segments of the lower lobes which had the lowest diagnostic yield (84.2% vs 64.7%, respectively). Nodules in the upper lobes and in the middle lobes had a diagnostic yield of 70% and 66.7%, respectively. CONCLUSION: The diagnostic performance of CT-guided biopsy of lung nodules ≤10 mm in diameter may be affected by lobar and segmental location. While the overall performance was good (diagnostic yield of 71%), the yield varied nearly 20% depending on location.


Assuntos
Biópsia Guiada por Imagem/métodos , Lesões Pré-Cancerosas/diagnóstico por imagem , Adulto , Idoso , Biópsia por Agulha/métodos , Feminino , Humanos , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos , Lesões Pré-Cancerosas/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
9.
Cochrane Database Syst Rev ; 5: CD007334, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32442322

RESUMO

BACKGROUND: Barrett's oesophagus is one of the most common pre-malignant lesions in the world. Currently the mainstay of therapy is surgical management of advanced cancer but this has improved the five-year survival very little since the 1980s. As a consequence, improved survival relies on early detection through endoscopic surveillance programmes. Success of this strategy relies on the fact that late-stage pre-malignant lesions or very early cancers can be cured by intervention. Currently there is considerable controversy over which method is best: that is conventional open surgery or endotherapy (techniques involving endoscopy). OBJECTIVES: We used data from randomised controlled trials (RCTs) to examine the effectiveness of endotherapies compared with surgery in people with Barrett's oesophagus, those with early neoplasias (defined as high-grade dysplasia (HGD) and those with early cancer (defined as carcinoma in-situ, superficially invasive, early cancer or superficial cancer T-1m (T1-a) and T-1sm (T1-b)). SEARCH METHODS: We used the Cochrane highly sensitive search strategy to identify RCTs in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, EBMR, Controlled Trials mRCT and ISRCTN, and LILACS, in July and August 2008. The searches were updated in 2009 and again in April 2012. SELECTION CRITERIA: Types of studies: RCTs comparing endotherapies with surgery in the treatment of high-grade dysplasia or early cancer. All cellular types of cancer were included (i.e. adenocarcinomas, squamous cell carcinomas and more unusual types) but will be discussed separately. TYPES OF PARTICIPANTS: patients of any age and either gender with a histologically confirmed diagnosis of early neoplasia (HGD and early cancer) in Barrett's or squamous lined oesophagus. Types of interventions; endotherapies (the intervention) compared with surgery (the control), all with curative intent. DATA COLLECTION AND ANALYSIS: Reports of studies that meet the inclusion criteria for this review would have been analysed using the methods detailed in Appendix 9. MAIN RESULTS: We did not identify any studies that met the inclusion criteria. In total we excluded 13 studies that were not RCTs but that compared surgery and endotherapies. AUTHORS' CONCLUSIONS: This Cochrane review has indicated that there are no RCTs to compare management options in this vital area, therefore trials should be undertaken as a matter of urgency. The problems with such randomised methods are standardising surgery and endotherapies in all sites, standardising histopathology in all centres, assessing which patients are fit or unfit for surgery and making sure there are relevant outcomes for the study (i.e. long-term survival (over five or more years)) and no progression of HGD.


Assuntos
Esôfago de Barrett/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagoscopia/métodos , Lesões Pré-Cancerosas/cirurgia , Esôfago de Barrett/patologia , Neoplasias Esofágicas/patologia , Humanos , Lesões Pré-Cancerosas/patologia
10.
Science ; 368(6487)2020 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-32273439

RESUMO

Metabolic reprogramming is a hallmark of malignancy. As our understanding of the complexity of tumor biology increases, so does our appreciation of the complexity of tumor metabolism. Metabolic heterogeneity among human tumors poses a challenge to developing therapies that exploit metabolic vulnerabilities. Recent work also demonstrates that the metabolic properties and preferences of a tumor change during cancer progression. This produces distinct sets of vulnerabilities between primary tumors and metastatic cancer, even in the same patient or experimental model. We review emerging concepts about metabolic reprogramming in cancer, with particular attention on why metabolic properties evolve during cancer progression and how this information might be used to develop better therapeutic strategies.


Assuntos
Neoplasias/metabolismo , Neoplasias/patologia , Animais , Progressão da Doença , Humanos , Camundongos , Terapia de Alvo Molecular , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias/terapia , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia
11.
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
12.
BJOG ; 127(8): 994-999, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32133762

RESUMO

OBJECTIVE: The aim of this study was to evaluate the incidence of endometrial carcinoma, proven after hysterectomy, in patients diagnosed with atypical endometrial hyperplasia confined to a polyp. A secondary aim was to establish factors associated with (pre-)malignant alterations in a polyp. DESIGN: A retrospective cohort study. SETTING: Maastricht University Medical Centre (MUMC+) and Máxima Medical Centre in Eindhoven/Veldhoven (Máxima MC). POPULATION: Women who underwent a hysteroscopic polyp resection between 2008 and 2016. METHODS: Patient characteristics and histopathology results of the polyp and, in the case of a hysterectomy, uterus were collected from patients' charts. RESULTS: A total of 1445 complete hysteroscopic polyp resections were included. Of those, 1390 polyps showed benign histopathology results, 39 polyps contained atypical hyperplasia and 16 polyps contained endometrial carcinoma. A hysterectomy was performed in 35 women who were diagnosed with atypical hyperplasia confined to a polyp after hysteroscopic polyp resection. Histopathological assessment showed no additional (pre-)malignant changes of the endometrium in 12 women (30.8%), atypical hyperplasia in 11 women (28.2%) and endometrial carcinoma in 12 women (30.8%). None of the prognostic factors under consideration were significantly associated with (pre-)malignant changes in a polyp. CONCLUSION: The incidence of endometrial carcinoma in the surrounding endometrium after complete resection of a polyp with atypical hyperplasia is 30.8% in this study. This supports the current advice to perform a hysterectomy and bilateral salpingo-oophorectomy. No prognostic factor for (pre-)malignant changes in a polyp was established. TWEETABLE ABSTRACT: The incidence of endometrial carcinoma after complete resection of a polyp with atypical hyperplasia is high.


Assuntos
Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/patologia , Pólipos/patologia , Lesões Pré-Cancerosas/patologia , Adulto , Hiperplasia Endometrial/cirurgia , Neoplasias do Endométrio/prevenção & controle , Endométrio/patologia , Feminino , Humanos , Histerectomia , Incidência , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/complicações , Estudos Retrospectivos , Útero/patologia
13.
Radiology ; 295(2): 448-455, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32181731

RESUMO

Background It remains unclear whether 5 years of stability is sufficient to establish the benign behavior of subsolid nodules (SSNs) of the lung. There are no guidelines for the length of follow-up needed for these SSNs. Purpose To investigate the incidence of interval growth of pulmonary SSNs 6 mm or greater in diameter after 5 years of stability and their clinical outcome. Materials and Methods This retrospective study assessed SSNs 6 mm or greater that were stable for 5 years after detection (January 2002 to December 2018). The incidence of interval growth after 5 years of stability and the clinical and radiologic features of these SSNs were investigated. Clinical stage shifts of growing SSNs, presence of metastasis, and overall survival were assessed during the follow-up period. Subgroup analysis was performed in patients with nonenhanced thin-section (section thickness ≤1.5 mm) CT for interval growth after 5 years of stability. Results A total of 235 SSNs in 235 patients (mean age, 64 years ± 10 [standard deviation]; 132 women) were evaluated. There were 212 pure ground-glass nodules and 24 part-solid nodules. During follow-up (median, 112 months; range, 84-208 months), five of the 235 SSNs (2%; three primary ground-glass nodules and two part-solid nodules) showed interval growth. Three of these five growing SSNs were 10 mm or greater. Three of the five SSNs with interval growth had clinical stage shifts after growth (from Tis [in situ] to T1mi [minimally invasive] in one lesion; from T1mi to T1a in two lesions). There were no deaths or metastases from lung cancer during follow-up. Of 160 SSNs imaged with section thickness of 1.5 mm or less, two (1%) grew; both lesions were 10 mm or greater. Conclusion Only 2% of subsolid pulmonary nodules greater than or equal to 6 mm that had been stable for 5 years showed subsequent growth. At median follow-up of 9 years (after the initial 5-year period of stability), growth of those lung nodules had no clinical effect. © RSNA, 2020 See also the editorial by Naidich and Azour in this issue.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/patologia , Radiografia Torácica/métodos , Tomografia Computadorizada por Raios X/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Lesões Pré-Cancerosas/diagnóstico por imagem , Lesões Pré-Cancerosas/patologia , Estudos Retrospectivos
14.
Arch Oral Biol ; 113: 104688, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32146149

RESUMO

OBJECTIVE: investigate the T102C polymorphism of 5HT2A receptor in dysplasia in oral potentially malignant lesions and its association with smoking and alcohol habits. METHODS: case-control study that included patients with oral potentially malignant lesions (OPML) histopathologically diagnosed with dysplasia and healthy controls, and within these group patients with and without smoking and alcohol consumption habits. Cell samples from the oral lesions were collected with the patients previously anesthetized using disposable cytological brushes. Deoxyribonucleic acid (DNA) extraction was performed and the T102C polymorphism (rs6313) was genotyped in a real-time polymerase chain reaction (PCR) allelic discrimination assays. RESULTS: 110 individuals were included in this study (38 with dysplasia and 72 controls). The genotype (p = 0.016), allele (p = 0.020) and smoking habits (<0.001) distribution differed significantly between dysplasia and control group, where the CT and TT (C - cytosine/ T - thymine) genotype and the T allele showed a higher frequency in dysplasia (65.6, 18.8 and 84.4 %, respectively) than in controls (55.7, 4.9 and 60.7). Concerning smoking habits, the higher frequency was in the dysplasia group. The multivariate logistic regression analysis, associating variables of interest and the presence of dysplasia, showed that individuals with smoking habits present 7.58 increase risk to develop dysplasia than non-smokers; and individuals carrying the T allele for the T102C polymorphism have a 4.6 increased risk to develop oral dysplasia in OPML. CONCLUSIONS: the T102C polymorphism is associated with oral dysplasia in OPML, however, failed to show association with smoking and alcohol habits in OPML dysplasia.


Assuntos
Mucosa Bucal/patologia , Polimorfismo Genético , Receptor 5-HT2A de Serotonina/genética , Alelos , Estudos de Casos e Controles , Epitélio/patologia , Genótipo , Humanos , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia
15.
J Pathol ; 251(2): 135-146, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32207854

RESUMO

Intestinal-type gastric cancer (IGC) has a clear and multistep histological evolution. No studies have comprehensively explored gastric tumorigenesis from inflammation through low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia (HGIN) to early gastric cancer (EGC). We sought to investigate the characteristics participating in IGC tumorigenesis and identify related prognostic information within the process. RNA expression profiles of 94 gastroscopic biopsies from 47 patients, including gastric precancerous lesions (GPL: LGIN and HGIN), EGC, and paired controls, were detected by Agilent Microarray. During IGC tumorigenesis from LGIN through HGIN to EGC, the number of activity-changed tumor hallmarks increased. LGIN and HGIN had similar expression profiles when compared to EGC. We observed an increase in the stemness of gastric epithelial cells in LGIN, HGIN, and EGC, and we found 27 consistent genes that might contribute to dedifferentiation, including five driver genes. Remarkably, we perceived that the immune microenvironment was more active in EGC than in GPL, especially in the infiltration of lymphocytes and macrophages. We identified a five-gene signature from the gastric tumorigenesis process that could independently predict the overall survival and disease-free survival of GC patients (log-rank test: p < 0.0001), and the robustness was verified in an independent cohort (n > 300) and by comparing with two established prognostic signatures in GC. In conclusion, during IGC tumorigenesis, cancer-like changes occur in LGIN and accumulate in HGIN and EGC. The immune microenvironment is more active in EGC than in LGIN and HGIN. The identified signature from the tumorigenesis process has robust prognostic significance for GC patients. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.


Assuntos
Carcinoma in Situ/genética , Transformação Celular Neoplásica/genética , Perfilação da Expressão Gênica , Lesões Pré-Cancerosas/genética , Neoplasias Gástricas/genética , Transcriptoma , Carcinoma in Situ/imunologia , Carcinoma in Situ/mortalidade , Carcinoma in Situ/patologia , Transformação Celular Neoplásica/imunologia , Transformação Celular Neoplásica/patologia , Intervalo Livre de Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Linfócitos do Interstício Tumoral/imunologia , Macrófagos/imunologia , Gradação de Tumores , Células-Tronco Neoplásicas/patologia , Lesões Pré-Cancerosas/imunologia , Lesões Pré-Cancerosas/mortalidade , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Microambiente Tumoral
18.
PLoS One ; 15(2): e0229089, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32092078

RESUMO

PURPOSE: The tumor-related myeloid derived suppressor cells (MDSCs), important immunosuppressive cells in tumor microenvironment, play an important role in the cancer progression. This study is aimed to investigate the crosstalk between MDSCs and oral squamous cell carcinoma (OSCC) cells and their role in the malignant progression of OSCC. METHODS: Immunochemistry (IHC) was used to investigate the expression of CD33 in 200 OSCC, 36 premalignant. CD33+ MDSCs were sorted and enriched via magnetic-activated cell sorting (MACS) from OSCC patients or health donor, and their phenotypes were identified by flow cytometry. With a co-culture system of MDSCs and OSCC, the effects of MDSCs on OSCC proliferation, apoptosis, migration invasion, epithelial-mesenchymal transition (EMT), and vasculogenic mimicry formation (VM) formation were assessed, respectively. Besides, peripheral blood mononuclear cells (PBMCs) from health donor were cultured with OSCC supernatant, the level of MDSCs and expressions of Arginase (Arg-1) and inducible nitric oxide synthase (iNOS) were measured. RESULTS: The number of MDSCs was increased in tumor tissues of OSCC patients, and was positively related to the T stage, pathological grade, lymph node metastasis and poor prognosis. Tumor-related MDSCs of the co-culture system promoted OSCC progression by contributing to cell proliferation, migration and invasion as well as inducing EMT and VM. In turn, OSCC cells had potential to induce MDSCs differentiation from PBMCs and increase the expression of Arg-1 and iNOS. CONCLUSION: These indicated that the crosstalk between MDSCs and tumor cells facilitated the malignant progression of OSCC cells and the immune suppressive properties of MDSCs, which may provide new insights into tumor treatment on targeting tumor-associated immunosuppressive cells.


Assuntos
Carcinogênese/imunologia , Neoplasias Bucais/patologia , Células Supressoras Mieloides/imunologia , Lesões Pré-Cancerosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinogênese/patologia , Comunicação Celular/imunologia , Células Cultivadas , Técnicas de Cocultura , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/sangue , Neoplasias Bucais/imunologia , Neoplasias Bucais/cirurgia , Estadiamento de Neoplasias , Lesões Pré-Cancerosas/imunologia , Cultura Primária de Células , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Células Tumorais Cultivadas , Microambiente Tumoral/imunologia
19.
Braz Oral Res ; 34: e002, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32049107

RESUMO

Oral potentially malignant disorders (OPMD) possess significant chances of malignancy conversion. In order to develop an early diagnostic tool, the present study evaluated the expression of miRNA-21 and 31 as salivary markers. The case-control study was carried out in 36 healthy participants as controls and in 36 patients who were newly diagnosed as OPMD having four different lesions including leucoplakia, oral sub mucous fibrosis (OSMF)궱, oral lichen planus, and (OSMF)궱 with leucoplakia. The samples were also classified as non-dysplastic, or with mild, moderate, and severe dysplasia according to their histopathological reports. The salivary miRNA-21 and 31 expressions were studied using real-time PCR. The statistical analysis was carried out using SPSS version 22. Salivary miRNA-21 (p-value = 0.02) and 31 (p-value = 0.01) were significantly upregulated in severe dysplasia compared with control. Among the different lesions, leucoplakia had significant upregulation of miRNA-21 and 31. miRNA-21 can be used as a diagnostic marker with specificity of 66% and sensitivity of 69%. The area under the ROC curve was 0.820 for miRNA-21 and 0.5 for miRNA-31, which proved that miRNA-21 is a better diagnostic marker than miRNA-31 for OPMD.


Assuntos
MicroRNAs/análise , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/patologia , Saliva/química , Análise de Variância , Biomarcadores Tumorais/análise , Estudos de Casos e Controles , Humanos , Leucoplasia Oral/patologia , Líquen Plano Bucal/patologia , Modelos Lineares , Neoplasias Bucais/química , Fibrose Oral Submucosa/patologia , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Índice de Gravidade de Doença
20.
J Surg Res ; 250: 226-231, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32106001

RESUMO

BACKGROUND: Gallbladder cancer is rare but associated with significant morbidity and mortality necessitating the early identification of premalignant and malignant lesions to improve overall prognosis. Despite limited evidence regarding the effectiveness of transabdominal ultrasound (US) in the detection of gallbladder polyps, it plays a key role in current European guidelines. The aim of this study was to investigate gallbladder polyp prevalence in a western European population and assess the diagnostic accuracy of transabdominal US. METHODS: Data from patients who underwent cholecystectomy for US detected gallbladder polypoid lesions at four hospitals in Ireland and the United Kingdom between 2010 and 2018 were retrospectively collected. Patient demographics, ultrasonographic, and histopathologic findings were analyzed. RESULTS: A total of 134 patients underwent cholecystectomy for US-detected gallbladder polyps. After histopathologic examination, pseudopolyps were found in 75 (56%) specimens with dysplastic or malignant polyps seen in only six (4.5%) specimens. Mean size for neoplastic polyps was 33 mm. The positive predictive value for US in detecting neoplastic polyps in this study was 4.5%, which is significantly lower than the 10%-15% reported previously. CONCLUSIONS: Although the prevalence of neoplastic polyps in this study is higher than in the previous literature, the distribution of pseudopolyps and true polyps is as expected. With all malignant polyps being >10 mm in diameter, these findings support the current size thresholds stated in European guidelines. The poor diagnostic accuracy of US demonstrated may have led to significant number of patients undergoing unnecessary surgical intervention, further supporting the argument for improved strategies for the investigation of gallbladder polyps.


Assuntos
Neoplasias da Vesícula Biliar/epidemiologia , Vesícula Biliar/diagnóstico por imagem , Pólipos/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Colecistectomia/estatística & dados numéricos , Feminino , Vesícula Biliar/patologia , Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Irlanda/epidemiologia , Masculino , Pessoa de Meia-Idade , Pólipos/diagnóstico , Pólipos/patologia , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/cirurgia , Valor Preditivo dos Testes , Prevalência , Estudos Retrospectivos , Ultrassonografia/estatística & dados numéricos , Reino Unido/epidemiologia , Adulto Jovem
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