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1.
Medicine (Baltimore) ; 99(35): e21895, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871920

RESUMO

MicroRNAs (miRNAs) refers to a small, short non-coding RNA of endogenous class. They have shown to have an increasingly altered expression in many types of cancer, including colorectal cancer (CRC).In the present study, miRNA TaqManMGB and qRT-PCR was used to quantify the expression and clinical significance of 3 mature human miRNA in 82 pairs of colorectal adenocarcinoma tissues and normal adjacent tissue samples (NATS) collected from patients of the south-east part of Romania. Differences between CRC and NATS were analyzed using Wilcoxon test, while correlations between miRNAs expression levels and clinicopathological features were examined using non-parametric tests. In addition, the ability of selected miRNAs to function as biomarkers and, as potential indicators in CRC prognosis was also examined.When the miRNA expression was compared in CRC related NATS, miR-143, and miR-145 were significantly underexpressed (4.99 ±â€Š-1.02 vs -5.66 ±â€Š-1.66, P < .001; -4.85 ±â€Š-0.59 vs -9.27 ±â€Š-1.51, P < .001, respectively), while the pattern of miR-92a was significantly overexpressed (-5.55 ±â€Š-2.83 vs -4.92 ±â€Š-2.44, P < .001). Moreover, the expression levels of selected miRNAs were identified to be correlated with gradual increases in fold change expression with the depth of tumor invasion, lymph node invasion, and maximal increases with distant metastasis. Furthermore, the receiver operating characteristic analysis demonstrated that potential diagnostic of miR-143, miR-145, and miR-92a in discriminating CRC from NATS, with the area under the curve of 0.74, 0.85, and 0.84 respectively. The Kaplan-Meier and the log-rank test showed that a high level of miR-92a and low levels of miR-143 and miR-145 predicted poor survival rate in our cohorts.In conclusion, we can summarize that miR-145 and miR-143 are decreased, while miR-92 is increased in CRC compared to NATS, and associated with different stages of CRC pathogenesis. Thus, the expression of selected miRNAs can represent potential diagnostic and prognostic tools in patients with CRC from Romania.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , MicroRNAs/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Idoso , Área Sob a Curva , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Romênia , Transcriptoma
2.
Chirurgia (Bucur) ; 115(4): 448-457, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32876018

RESUMO

Background: In Romania, colorectal cancer does not benefit yet from a national screening program. In order to decrease the harm and burden of colorectal cancer (CRC), opportunistic programs relying on endoscopy has been adopted by each centre according to its capacity. A colorectal cancer (CRC) screening programme based on faecal immunochemical test (FIT) was launched at Ponderas Academic Hospital (PAH) in 2019. Aim: The present study analyses the outcomes after the first 1500 tests in the PAH-FIT-CRC Screening Program. We have also aimed to compare the efficiency of the FIT testing program with the screening colonoscopies performed in our Center, withing the same time interval (2019). Methods: The test was recommended in asymptomatic patients over 45 years, and it was followed by a colonoscopy when the test results were positive. Furthermore, we performed a retrospective observational study gathering data from all the consecutive patients prospectively included in the respective databases of our hospital, comparing the efficacy of the two colorectal cancer screening methods (FIT versus colonoscopy). Results: Between 01.01.2019 and 01.01.2020, 1524 screening colonoscopies were performed, and the resulting data were compared with those obtained in the FIT group (1500 FIT tests freely distributed). In the screening colonoscopy group, the polyp detection rate was 38.98% and 22 (1.44%) adenocarcinomas were identified. In the FIT group, the FIT uptake rate was 71% with a positivity rate of 21.7%. The colonoscopy compliance rate for positive FIT patients was 29.4%, with only 2 adenocarcinomas detected. Conclusions: Following data analysis, the need for improvement of uptake rate and colonoscopy compliance rate was suggested, due to the lower acceptance of FIT tests and colonoscopies, especially among men. Moreover, special efforts should be made in order to improve quality indicators for screening colonoscopies (especially adenoma detection rate) with the purpose of decreasing interval CRC.


Assuntos
Adenocarcinoma/diagnóstico , Pólipos Adenomatosos/diagnóstico , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Fezes , Colonoscopia , Fezes/química , Humanos , Masculino , Programas de Rastreamento/métodos , Estudos Retrospectivos , Romênia , Resultado do Tratamento
3.
Value Health ; 23(8): 1087-1095, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32828222

RESUMO

OBJECTIVES: The increasing incidence of esophageal adenocarcinoma (EAC) and the dismal prognosis has stimulated interest in the early detection of EAC. Our objective was to determine individuals' preferences for EAC screening and to assess to what extent procedural characteristics of EAC screening tests predict willingness for screening participation. METHODS: A discrete choice experiment questionnaire was sent by postal mail to 1000 subjects aged 50 to 75 years who were randomly selected from the municipal registry in the Netherlands. Each subject answered 12 discrete choice questions of 2 hypothetical screening tests comprising 5 attributes: EAC-related mortality risk reduction, procedure-related pain and discomfort, screening location, test specificity, and costs. A multinomial logit model was used to estimate individuals' preferences for each attribute level and to calculate expected rates of uptake. RESULTS: In total, 375 individuals (37.5%) completed the questionnaire. Test specificity, pain and discomfort, mortality reduction, and out-of-pocket costs all had a significant impact on respondents' preferences. The average expected uptake of EAC screening was 62.8% (95% confidence interval [CI] 61.1-64.5). Severe pain and discomfort had the largest impact on screening uptake (-22.8%; 95% CI -26.8 to -18.7). Male gender (ß 2.81; P < .001), cancer worries (ß 1.96; P = .01), endoscopy experience (ß 1.46; P = .05), and upper gastrointestinal symptoms (ß 1.50; P = .05) were significantly associated with screening participation. CONCLUSIONS: EAC screening implementation should consider patient preferences to maximize screening attendance uptake. Based on our results, an optimal screening test should have high specificity, cause no or mild to moderate pain or discomfort, and result in a decrease in EAC-related mortality.


Assuntos
Adenocarcinoma/diagnóstico , Técnicas de Apoio para a Decisão , Detecção Precoce de Câncer/psicologia , Neoplasias Esofágicas/diagnóstico , Preferência do Paciente , Comportamento de Escolha , Análise Custo-Benefício , Feminino , Humanos , Modelos Logísticos , Masculino , Países Baixos
4.
APMIS ; 128(11): 563-572, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32794589

RESUMO

Neuroendocrine tumors (NETs) are often diagnosed from the metastases of an unknown primary tumor. Specific immunohistochemical (IHC) markers indicating the location of a primary tumor are needed. The proprotein convertase subtilisin/kexin type 2 (PCSK2) is found in normal neural and neuroendocrine cells, and known to express in NETs. We investigated the tissue microarray (TMA) of 86 primary tumors from 13 different organs and 9 metastatic NETs, including primary tumor-metastasis pairs, for PCSK2 expression with polymer-based IHC. PCSK2 was strongly positive in all small intestine and appendiceal NETs, the so-called midgut NETs, in most pheochromocytomas and paragangliomas, and in some of the typical and atypical pulmonary carcinoid tumors. NETs showing strong positivity were re-evaluated in larger tumor cohorts confirming the primary observation. In the metastases, the expression of PCSK2 mirrored that of the corresponding primary tumors. We found negative or weak staining in NETs from the thymus, gastric mucosa, pancreas, rectum, thyroid, and parathyroid. PCSK2 expression did not correlate with Ki-67 in well-differentiated NETs. Our data suggest that PCSK2 positivity can indicate the location of the primary tumor. Thus, PCSK2 could function in the IHC panel determined from screening metastatic NET biopsies of unknown primary origins.


Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Carcinoma Neuroendócrino/genética , Neoplasias Gastrointestinais/genética , Neoplasias Pulmonares/genética , Tumores Neuroendócrinos/genética , Paraganglioma/genética , Feocromocitoma/genética , Pró-Proteína Convertase 2/genética , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Biomarcadores Tumorais/genética , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/cirurgia , Cromogranina A/genética , Feminino , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/cirurgia , Expressão Gênica , Humanos , Imuno-Histoquímica , Antígeno Ki-67/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Paraganglioma/diagnóstico , Paraganglioma/patologia , Paraganglioma/cirurgia , Feocromocitoma/diagnóstico , Feocromocitoma/patologia , Feocromocitoma/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia
6.
Anticancer Res ; 40(7): 4029-4032, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620648

RESUMO

The synchronous diagnosis of two or more primary malignancies in a patient is overall rare. This is a case report of a 70-year-old female with a history of skin squamous cell carcinoma presenting with occult hematochezia. Colonoscopy and biopsy results confirmed a microsatellite stable (MMS) adenocarcinoma in the ascending colon, and subsequent computed tomography (CT) scans identified a 3.2 cm right colonic mass and a 5.0 cm mass in the pancreatic body. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) confirmed the presence of pancreatic ductal adenocarcinoma (PDAC). The patient underwent neo-adjuvant FOLFIRINOX (folinic acid, fluorouracil, irinotecan and oxaliplatin) chemotherapy prior to the simultaneous distal pancreatectomy and right hemicolectomy for both pancreatic and colonic tumors. The pathology diagnoses included moderately differentiated pancreatic ductal carcinoma (PDAC) with histiocyte-like features (tumor stage: ypT3N1M0) and moderately differentiated colonic adenocarcinoma, intestinal type (tumor stage: ypT3N0M0). To the best of our knowledge, this is the first documented case of synchronous primary colonic adenocarcinoma and PDAC in the English literature.


Assuntos
Adenocarcinoma/diagnóstico , Carcinoma Ductal Pancreático/diagnóstico , Neoplasias do Colo/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adenocarcinoma/patologia , Idoso , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/patologia , Carcinoma de Células Escamosas , Neoplasias do Colo/patologia , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Neoplasias Primárias Múltiplas/patologia , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/patologia , Neoplasias Cutâneas
7.
Medicine (Baltimore) ; 99(29): e21215, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702890

RESUMO

RATIONALE: Penile metastasis in rectal cancer is very rare and often originates from prostatic or bladder cancer. The prognosis of penile metastasis is poor and its treatments are more often palliative than curative due to association with disseminated metastases. Pathologic complete response (pCR) in rectal cancer with neoadjuvant chemoradiotherapy (CRT) has been shown to be surrogate marker of favorable long-term outcomes and currently has no report of penile metastasis. Here, we first report isolated penile metastasis in rectal cancer with pCR after neoadjuvant CRT. PATIENT CONCERN: The patient was a 74-year-old male with metastasis to the glans penis from rectal cancer diagnosed 9 months after abdominoperineal resection. Physical examination revealed palpable multiple nodules on the glans penis. DIAGNOSIS: Penile biopsy revealed metastatic carcinoma from the rectal cancer. INTERVENTION: Chemotherapy was started as soon as possible, because patient suffered urinary discomfort by rapid growing metastatic lesions. He is currently receiving palliative chemotherapy with modified FOLFOX-6 (mFOLFOX-6; oxaliplatin with 5-fluorouracil and folinic acid) plus bevacizumab. OUTCOME: The patient is still alive 4 months after diagnosis with markedly decreased metastatic lesions. LESSON: We propose that although penile metastasis in rectal cancer with pCR after preoperative neoadjuvant CRT is extremely rare, it might help to start early palliative chemotherapy and clinicians should be aware of this possibility.


Assuntos
Adenocarcinoma/diagnóstico , Neoplasias Penianas/diagnóstico , Pênis , Neoplasias Retais/diagnóstico , Adenocarcinoma/secundário , Adenocarcinoma/terapia , Idoso , Quimiorradioterapia , Diagnóstico Diferencial , Humanos , Masculino , Terapia Neoadjuvante , Metástase Neoplásica , Neoplasias Penianas/secundário , Neoplasias Penianas/terapia , Neoplasias Retais/patologia , Neoplasias Retais/terapia
8.
Medicine (Baltimore) ; 99(29): e21287, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702921

RESUMO

The potential association between the prognosis of the pancreatic adenocarcinoma (PAAD) and its microenvironment is unclear. This study aims to construct a prognostic index (PI) model of the PAAD microenvironment to predict PAAD patient survival outcomes.The mRNA sequencing and the clinical parameters data were obtained from The Cancer Genome Atlas. Immune and stromal scores were computed using the expression data algorithm to capture infiltration of immune and stromal cells in the PAAD tissue, where patients were categorized as high and low score groups according to these scores. Differentially expressed genes were identified using the R package LIMMA. Univariate and multivariate Cox regression analysis were conducted to select candidate survival-correlated gene signatures from the tumor microenvironment for constructing a model. The Kaplan-Meier method was used to access overall survival of the primary and validation cohorts. The immunological features of the PI model was explored using the Tumor Immune Estimation Resource (TIMER) database. Bioinformatic analyses were conducted based on the DAVID database.A total of 1266 overlapping differentially expressed genes and 49 prognosis-associated genes were identified. A 7-mRNA signature (GBP5, BICC1, SLC7A14, CYSLTR1, P2RY6, VENTX, and RAB39B) was screened for the construction of a PI model (area under the curve = 0.791). In both the primary and validation cohorts, Kaplan Meier analysis revealed that the overall survival of the high-risk group was significantly worse compared to the low-risk group (P < .0001, P = .0028 respectively). The TIMER database described that the 7 signature genes were correlated with immune infiltrating cells and tumor purity. Bioinformatic analyses revealed that these prognosis-associated genes were significantly enriched during inflammation, the defense response, would response, calcium ion transport, and plasma membrane part.A list of the prognosis-correlated genes was generated based on the PAAD microenvironment. A 7-mRNA PI model may be used for predicting the prognosis of PAAD patients.


Assuntos
Adenocarcinoma/metabolismo , Neoplasias Pancreáticas/metabolismo , RNA Mensageiro/metabolismo , RNA Neoplásico/metabolismo , Microambiente Tumoral , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Transcriptoma
9.
Medicine (Baltimore) ; 99(27): e20941, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629697

RESUMO

RATIONALE: Tailgut cyst (TGC) is a rare congenital disease that originates from residues of the tail intestine during the embryonic period. Most TGCs are benign lesions and the malignant transition is very rare. PATIENT CONCERNS: A 50-year-old woman attended our department complaining of defecation difficulty for more than 2 months. She reported irregular defecation with a small amount of liquid stool, 3 to 4 times per day. DIAGNOSIS: Biochemical analysis showed high levels of carcinoembryonic antigen (79.89 ng/mL; normal, 0-3 ng/mL) and carbohydrate antigen 199 (57.60 U/mL; normal, 0-35 U/mL). Abdominal computer tomography and magnetic resonance imaging showed a large cystic mass with enhanced signals. Post-surgical histopathology indicated that the mass was a TGC with adenocarcinoma transition. INTERVENTIONS: The cyst was completely resected. Symptomatic treatment was further performed, and the patient recovered well. LESSONS: We reported a rare case of a large TGC with adenocarcinoma transition. CT, MRI, and histopathology are important to diagnose TGC. Complete surgical resection is the first choice to treat TGC.


Assuntos
Adenocarcinoma/diagnóstico , Cistos/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Retais/diagnóstico , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Biomarcadores Tumorais/sangue , Antígeno Carcinoembrionário/sangue , Cistos/diagnóstico por imagem , Cistos/patologia , Cistos/cirurgia , Diagnóstico Diferencial , Feminino , Proteínas Ligadas por GPI/sangue , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Tomografia Computadorizada por Raios X
10.
Rev Assoc Med Bras (1992) ; 66(5): 590-595, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32638965

RESUMO

OBJECTIVE Thrombopoietin (THPO) is well-known as a megakaryocyte growth and development factor (MGDF) involved in megakaryocyte proliferation and maturation. To explore the biological effects of THPO in gastric adenocarcinoma, we conducted this study. Methods: By accessing the TCGA database, the expression level of THPO was determined in tumor tissues. The association between THPO expression and clinical features, or prognostic significance was described by Cox regression analysis and Kaplan-Meier. The SiRNA method was used to decline the THPO expression; then cell viability, invasion, and migration were detected to verify the effects of the knockdown of THPO. qPCR and western blotting were implemented to examine the expression level of THPO. Results: The expression of THPO was increased in tumor tissue and cells, its high-regulation was associated with a poor prognosis in patients with gastric adenocarcinoma. Cell viability, invasion, and migration were suppressed in AGS with the down-regulation of THPO. Furthermore, on the basis of si-THPO transfection, E-cadherin was promoted while N-cadherin and Vimentin were attenuated. CONCLUSION Our results revealed that THPO may be a potent marker of gastric adenocarcinoma, providing a novel potential screening method for gastric adenocarcinoma.


Assuntos
Adenocarcinoma/diagnóstico , Neoplasias Gástricas/diagnóstico , Trombopoetina/metabolismo , Adenocarcinoma/metabolismo , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , Prognóstico , Neoplasias Gástricas/metabolismo
11.
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
12.
PLoS One ; 15(6): e0233687, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32502149

RESUMO

Serum carcinoembryonic antigen (CEA) levels can help predict the prognosis of colorectal cancer patients. Accordingly, high preoperative CEA levels that is not restored after surgery are indicative of a worse outcome. On the other hand, smoking can increase serum CEA levels independently of the disease status. Thus, we aimed to evaluate the impact of smoking on the prognostic value of serum CEA levels. This retrospective cohort study included 273 patients who underwent curative resection for stage I-III colorectal adenocarcinoma at a single institution, between January 2010 and December 2017. Patients were grouped as follows: group A, normal preoperative and postoperative CEA levels (n = 152); group B, elevated preoperative CEA levels that returned to reference values after surgery (n = 69); and group C, elevated postoperative serum CEA levels (n = 52). Patients were also grouped according to their smoking history: group S (current smokers, n = 79) and group NS (never and former smokers, n = 194). Group A showed a higher 3-year disease-free survival (DFS) rate (84.9%) than groups B (75.4%) and C (62.0%) (p < 0.001). Postoperative serum CEA levels were significantly higher in the S group than in the NS group (2.6 vs. 3.1 ng/mL, p = 0.009), whereas preoperative levels were similar (3.8 vs. 4.1, p = 0.182). Further, smokers showed higher 3 year-DFS rates than nonsmokers in group C (83.3% vs. 43.9%, p = 0.029). This suggests that while elevated postoperative CEA levels are associated with lower DFS rates in never and former smokers, they are not associated with lower DFS rates in current smokers. We conclude that persistent smoking alters the prognostic value of postoperative serum CEA levels in colorectal cancer patients and that, consequently, alternative surveillance strategies need to be developed for colon cancer patients with smoking habits.


Assuntos
Adenocarcinoma/sangue , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/sangue , Fumar Tabaco/sangue , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Estudos de Coortes , Neoplasias Colorretais/complicações , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
13.
PLoS One ; 15(6): e0233782, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520974

RESUMO

Despite recent advances in clinical treatment, pancreatic cancer remains a highly lethal malignancy. In order to improve the survival rate of patients with pancreatic cancer, the development of non-invasive diagnostic methods using effective biomarkers is urgently needed. Here, we developed a highly sensitive method to detect DNA methylation in cell-free (cf)DNA samples based on the enrichment of methyl-CpG binding (MBD) protein coupled with a digital PCR method (MBD-ddPCR). Five DNA methylation markers for the diagnosis of pancreatic cancer were identified through DNA methylation microarray analysis in 37 pancreatic cancers. The sensitivity and specificity of the five markers were validated in another independent cohort of pancreatic cancers (100% and 100%, respectively; n = 46) as well as in The Cancer Genome Atlas data set (96% and 90%, respectively; n = 137). MBD-ddPCR analysis revealed that DNA methylation in at least one of the five markers was detected in 23 (49%) samples of cfDNA from 47 patients with pancreatic cancer. Further, a combination of DNA methylation markers and the KRAS mutation status improved the diagnostic capability of this method (sensitivity and specificity, 68% and 86%, respectively). Genome-wide MBD-sequencing analysis in cancer tissues and corresponding cfDNA revealed that more than 80% of methylated regions were overlapping; DNA methylation profiles of cancerous tissues and cfDNA significantly correlated with each other (R = 0.97). Our data indicate that newly developed MBD-ddPCR is a sensitive method to detect cfDNA methylation and that using five marker genes plus KRAS mutations may be useful for the detection of pancreatic cancers.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/genética , Metilação de DNA , Neoplasias Pancreáticas/genética , Adenocarcinoma/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/normas , Ilhas de CpG , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/normas , Feminino , Humanos , Masculino , Proteína 2 de Ligação a Metil-CpG/metabolismo , Pessoa de Meia-Idade , Mutação , Neoplasias Pancreáticas/diagnóstico , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/normas , Proteínas Proto-Oncogênicas p21(ras)/genética , Sensibilidade e Especificidade
14.
Medicine (Baltimore) ; 99(26): e20985, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590811

RESUMO

RATIONALE: Among the various forms of colorectal carcinomas, primary signet ring cell carcinoma (SRCC) of rectum is infrequent. Primary SRCC with adenoma is even rarer. Due to its low morbidity and lack of obvious manifestations at early stages, it is difficult to make an early diagnosis and perform surgical intervention in time. Herein, we reported a case of primary SRCC with tubular adenoma of rectum and also performed a review of the literature of such cases, in hopes of expanding the general understanding regarding such cases. PATIENT CONCERNS: A 61-year-old male patient presented with rectal bleeding for 1 week. DIAGNOSES: A neoplasm could be palpated through a rectal examination, with a size of 4.0 cm by 3.0 cm, at a distance of 5 cm from the anal edge. Magnetic resonance imaging examination and colonoscopies were performed to confirm the finding, and 4 tissue specimens were obtained for histopathologic biopsy. The result of biopsy was high-grade intraepithelial neoplasia with an adenoma component. INTERVENTIONS: Surgical resection was performed, and histopathologic and immunohistochemical staining examination of the resection confirmed the diagnosis of SRCC with tubular adenoma. OUTCOMES: The patient was discharged from hospital 12 days postsurgery, without any complications. Further chemotherapy and supportive treatments were suggested to him and will be followed at a local hospital. LESSONS: Primary rectal SRCC has a rather low morbidity. Furthermore, a rectal SRCC with adenoma which was presenting in this case is even more rare. Besides lack of clinical characters, delay of diagnosis and treatment frequently occur. So far, a surgical procedure has still been one of the most effective treatments. Considering of metastasis and the poor prognosis, early diagnosis, in-time radical resection, and a comprehensive followed treatment are recommended for a higher 5-year overall survival.


Assuntos
Adenocarcinoma/diagnóstico , Carcinoma de Células em Anel de Sinete/diagnóstico , Neoplasias Retais/diagnóstico , Adenocarcinoma/patologia , Carcinoma de Células em Anel de Sinete/patologia , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Neoplasias Retais/patologia , Reto/patologia , Resultado do Tratamento
15.
Medicine (Baltimore) ; 99(21): e20361, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481329

RESUMO

INTRODUCTION: Gastric adenocarcinoma of the fundic gland type (GA-FG) is a newly described entity that is characterized by well-differentiated neoplasm with unclear etiopathogenesis. PATIENT CONCERNS: A 60-year-old Chinese man was referred to our hospital for abdominal distension. DIAGNOSIS: Esophagogastroduodenoscopy (EGD) showed a depressed lesion found using in the greater curvature of the stomach. The pathological diagnosis of the biopsy specimens indicated that the tumor was GA-FG (chief cell predominant type, GA-FG-CCP). INTERVENTIONS: Endoscopic submucosal dissection (ESD) was performed. The histopathological examination of the ESD specimen revealed gastric hyperplasia of the fundic gland type around the adenocarcinoma cells. OUTCOMES: The surgical outcomes were good. The EGD showed a scar with no recurrence, and no symptoms were observed 1 year postoperatively during the follow-up. CONCLUSION: We present a rare case of a depressed lesion with a pathogenic expression suggesting gastric hyperplasia of the fundic gland type around the adenocarcinoma cells. Considering the origin of oxyntic mucosa, we consider that it may develop into GA-FG. To understand this issue better, similar cases should be monitored in the future.


Assuntos
Adenocarcinoma/diagnóstico , Mucosa Gástrica/anormalidades , Adenocarcinoma/diagnóstico por imagem , China , Ressecção Endoscópica de Mucosa/métodos , Endoscopia do Sistema Digestório/métodos , Feminino , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/fisiopatologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/patogenicidade , Humanos , Pessoa de Meia-Idade , Mucina-6/análise , Pepsinogênio A/análise
16.
Am J Gastroenterol ; 115(8): 1201-1209, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32558685

RESUMO

INTRODUCTION: Nonendoscopic Barrett's esophagus (BE) screening may help improve esophageal adenocarcinoma outcomes. We previously demonstrated promising accuracy of methylated DNA markers (MDMs) for the nonendoscopic diagnosis of BE using samples obtained from a capsule sponge-on-string (SOS) device. We aimed to assess the accuracy of these MDMs in an independent cohort using a commercial grade assay. METHODS: BE cases had ≥ 1 cm of circumferential BE with intestinal metaplasia; controls had no endoscopic evidence of BE. The SOS device was withdrawn 8 minutes after swallowing, followed by endoscopy (the criterion standard). Highest performing MDMs from a previous study were blindly assessed on extracted bisulfite-converted DNA by target enrichment long-probe quantitative amplified signal (TELQAS) assays. Optimal MDM combinations were selected and analyzed using random forest modeling with in silico cross-validation. RESULTS: Of 295 patients consented, 268 (91%) swallowed the SOS device; 112 cases and 89 controls met the pre-established inclusion criteria. The median BE length was 6 cm (interquartile range 4-9), and 50% had no dysplasia. The cross-validated sensitivity and specificity of a 5 MDM random forest model were 92% (95% confidence interval 85%-96%) and 94% (95% confidence interval 87%-98%), respectively. Model performance was not affected by age, gender, or smoking history but was influenced by the BE segment length. SOS administration was well tolerated (median [interquartile range] tolerability 2 [0, 4] on 10 scale grading), and 95% preferred SOS over endoscopy. DISCUSSION: Using a minimally invasive molecular approach, MDMs assayed from SOS samples show promise as a safe and accurate nonendoscopic test for BE prediction.


Assuntos
Adenocarcinoma/diagnóstico , Esôfago de Barrett/diagnóstico , Neoplasias Esofágicas/diagnóstico , Marcadores Genéticos , Adenocarcinoma/genética , Adenocarcinoma/patologia , Idoso , Área Sob a Curva , Esôfago de Barrett/genética , Esôfago de Barrett/patologia , Biópsia , Endoscopia por Cápsula , Estudos de Casos e Controles , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Esofagoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Estados Unidos
17.
Am J Clin Pathol ; 154(3): 394-402, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32525969

RESUMO

OBJECTIVES: A definitive diagnosis of malignancy may not be possible in pleural effusions. We report our experience with the diagnosis of suspicious for malignancy (SFM) in pleural effusion. METHODS: A search for pleural effusions diagnosed as SFM (2008-2018) was performed. Patient records and pathology reports were reviewed. Specimens were subdivided into groups depending on volume (<75, 75-400, >400 mL). Diagnoses of malignant pleural effusion (MPE) served as controls. RESULTS: We identified 90 patients, with a mean age of 60.6 years. Diagnoses included suspicious for involvement by carcinoma/adenocarcinoma in 64.4%, leukemia/lymphoma in 15.6%, melanoma in 2.2%, sarcoma in 3.3%, germ cell tumor in 1.1%, and not otherwise specified in 13.3%. Immunostains were performed in 47.8% and considered inconclusive in 24%. Average sample volume was 419 mL. There was a statistically significant difference between the SFM vs MPE groups for volumes greater than 75 mL (P = .001, χ 2 test), with SFM having increased proportion of volumes  greater than 400 mL, compared with the MPE group. There was no statistically significant difference in mean overall survival when the groups were compared (P = .49). CONCLUSIONS: Samples with low cellularity, scant cell blocks, and inconclusive immunostains may contribute to a suspicious category diagnosis in pleural effusions.


Assuntos
Adenocarcinoma/diagnóstico , Linfoma/diagnóstico , Derrame Pleural Maligno/diagnóstico , Derrame Pleural/patologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Citodiagnóstico , Feminino , Humanos , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Derrame Pleural Maligno/patologia , Sensibilidade e Especificidade , Adulto Jovem
18.
Cancer Sci ; 111(7): 2451-2459, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32359209

RESUMO

The causes of death in patients with gastric adenocarcinoma have not been well characterized. This nationwide population-based cohort study included 56 240 patients diagnosed with gastric adenocarcinoma in 1970-2014 in Sweden. We used competing-risks regression to compare cause-specific risks of death in patients with different characteristics and a multiple-cause approach to assess proportions of deaths attributable to each cause. Among 53 049 deaths, gastric cancer was the main (77.7% of all deaths) underlying cause. Other major underlying causes were nongastric malignancies (8.0%), ischemic heart disease or cerebrovascular disease (6.5%), and respiratory diseases (1.4%). Risk of death from gastric cancer steadily decreased in patients with cardia adenocarcinoma over the study period, but remained relatively stable in patients with noncardia adenocarcinoma since the 1980s. Risk of death from other malignancies increased during later calendar periods (subhazard ratio [SHR] = 2.16, 95% confidence interval [CI] 1.97-2.38, comparing 2001-2014 with 1970-1980). Compared with men, the risk of death in women with cardia adenocarcinoma was higher from gastric cancer (SHR = 1.18, 95% CI 1.10-1.27), but lower from other malignancies (SHR = 0.80, 95% CI 0.71-0.91). In multiple-cause models, 60.4%-71.2% of all deaths were attributable to gastric cancer and 9.5%-12.1% to other malignancies. The temporal trends of cause-specific risks from multiple-cause models were similar to those of underlying causes. Our findings suggest that although most deaths in patients with gastric adenocarcinoma are due to gastric cancer, other causes of death are common. Patients with cardia adenocarcinoma face considerable increasing risk of death from other causes over time, particularly from other malignancies.


Assuntos
Adenocarcinoma/epidemiologia , Causas de Morte , Neoplasias Gástricas/epidemiologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/história , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , História do Século XX , História do Século XXI , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Vigilância da População , Sistema de Registros , Suécia/epidemiologia
19.
Surg Clin North Am ; 100(3): 629-634, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32402305

RESUMO

Anal cancer is a rare cancer, comprising less than 5% of gastrointestinal tract malignancies. Diagnosis of anal canal cancer can be difficult given that presenting symptoms are similar to those of benign anorectal diseases. General surgeons who encounter suspected anal canal cancer need to have a good understanding of the anatomy of the anal canal, high index of suspicion for malignancy, and low threshold to biopsy lesions when indicated. This article discusses the most commonly encountered anal canal tumors, the evaluation of these tumors, and their management. The foundation for successful therapy includes timely diagnosis, accurate staging, and routine surveillance.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias do Ânus/cirurgia , Carcinoma Basocelular/cirurgia , Carcinoma de Células Escamosas/cirurgia , Melanoma/cirurgia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Canal Anal/patologia , Canal Anal/cirurgia , Neoplasias do Ânus/diagnóstico , Neoplasias do Ânus/patologia , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Diagnóstico Diferencial , Seguimentos , Metástase Linfática/patologia , Metástase Linfática/terapia , Melanoma/diagnóstico , Melanoma/patologia , Estadiamento de Neoplasias , Proctoscopia , Prognóstico
20.
J Cancer Res Ther ; 16(1): 127-131, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362622

RESUMO

Introduction: More than 70% of lung cancer comprises nonsmall-cell lung carcinoma and is associated with poor survival outcome owing to late diagnosis. Identification of lung cancer in early stages when no clinical signs or symptoms are evident, can drastically improve the prognosis. To this end, we aimed to evaluate the changes occurring at tissue level by assessing the expression of six microRNAs (miRNAs) in lung adenocarcinoma (AC) and squamous cell carcinoma (SCC). Materials and Methods: Peripheral blood of histopathologically proven cases of lung AC and SCC was collected and processed for the isolation of miRNAs using commercially available kit. Primers against mir-2114, mir-2115, mir-2116, mir-2117, mir-449c, and mir-548q with loading control Caenorhabditis elegans were used. Screening was carried out in thirty cases of both AC and SCC, whereas twenty healthy controls were included. Results: Real-time polymerase chain reaction data revealed that the expression of mir-2114 and mir-449c in AC and mir-2115 in SCC was significantly upregulated. The expression of these miRNAs was also confirmed in lung AC cell line. The differential pattern of expression of these miRNAs can be used for precise diagnosis of lung carcinoma. Conclusions: We have used a noninvasive technique to identify the subtype of lung cancer based on molecular genetic signatures. The results suggest that through molecular profiling of miRNA, we can screen high-risk cases for cancer interception.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , MicroRNA Circulante/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/diagnóstico , Adenocarcinoma/sangue , Adenocarcinoma/genética , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/genética , Estudos de Casos e Controles , MicroRNA Circulante/sangue , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Estadiamento de Neoplasias , Prognóstico
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