Perfil epidemiológico do câncer de colo do útero na Bahia (2015-2019)

Objetivo: caracterizar o perfil epidemiológico do câncer do colo de útero na Bahia entre os anos de 2015 a 2019. Metodologia: trata-se de estudo de abordagem quantitativa, descritivo dos casos com resultados de citologias positivas para câncer de colo do útero, identificados a partir de exames citopatológicos, registrados no Sistema de Informação do Câncer e disponíveis no Departamento de Informática do Sistema Único de Saúde, entre os anos de 2015 a 2019. Resultados: os anos com menor e maior número de realização de exames citopatológicos foram 2015 e 2019, respectivamente. Encontrou-se a cobertura de rastreamento de 32,0% para os anos de 2017 a 2019. O quantitativo de exames alterados apresentou aumento discreto no período analisado. Quanto à realização prévia da citologia foi identificado que 81% das mulheres já haviam realizado anteriormente, 11% realizaram o exame pela primeira vez, 7% com essa informação ignorada. Prevaleceram os intervalos de realização do exame entre 1 ano e 2 anos. O rastreamento foi o principal motivo de realização do exame. A variável escolaridade é demasiadamente subnotificada. O carcinoma epidermóide invasor foi o mais frequente (68,30%), seguido do adenocarcinoma In Situ (16,49%) e adenocarcinoma invasor (15,21%). A faixa etária mais acometida foi a de 35-44 anos (31,1%). Conclusão: o alto número de resultados alterados suscita ser emergente implementação de políticas proativas de modo que a prevenção e o diagnóstico precoce do câncer de colo uterino seja minimizado de forma expressiva. Estudos com esse delineamento constituem importantes ferramentas de identificação da real situação epidemiológica oportunizando melhor tomada de decisão.

Identification of pathological subtypes of early lung adenocarcinoma based on artificial intelligence parameters and CT signs

Objective: To explore the value of quantitative parameters of artificial intelligence and computed tomography (CT) signs in identifying pathological subtypes of lung adenocarcinoma appearing as ground-glass nodules (GGNs). Methods: CT images of 224 GGNs from 210 individuals were collected retrospectively and pathologically classified into atypical adenomatous hyperplasia (AAH)/adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) groups. Artificial intelligence was used to identify GGNs and to obtain quantitative parameters, and CT signs were recognized manually. The mixed predictive model based on logistic multivariate regression was evaluated. Results: Of the 224 GGNs, 55, 93, and 76 were AAH/AIS, MIA, IAC, respectively. In terms of artificial intelligence parameters, from AAH/AIS to MIA, and IAC, there was a gradual increase in two-dimensional mean diameter, three-dimensional mean diameter, mean CT value, maximum CT value, and volume of GGNs (all P < 0.0001). Except for the CT signs of the location, and the tumor-lung interface, there were significant differences among the three groups in the density type, shape, vacuole signs, air bronchogram, lobulation, spiculation, pleural indentation, and vascular convergence signs (all P < 0.05). The areas under the curve (AUC) of predictive model 1 for identifying the AAH/AIS and MIA and model 2 for identifying MIA and IAC were 0.779 and 0.918, respectively, which were greater than the quantitative parameters independently (all P < 0.05). Conclusion: Artificial intelligence parameters are valuable for identifying subtypes of early lung adenocarcinoma, and when combined with CT signs to improve its diagnostic efficacy.

Up-regulated tumor intrinsic growth potential and decreased immune function orchestrate the evolution of lung adenocarcinoma

Introduction Lung adenocarcinoma is the most common pathological subtype of lung cancer. Precursors of lung adenocarcinoma, namely adenocarcinoma in situ and minimally invasive adenocarcinoma, have a superb 5-year survival rate after surgical resection. A deeper understanding of the key genetic changes driving the progression of lung adenocarcinoma is needed. Methods In this study, we performed whole-exome sequencing and RNA-sequencing on surgically resected 24 AIS, 74 MIA, 99 LUAD specimens and their adjacent paired normal tissues. Radiological, clinical, and pathological characteristics were recorded. Gene expression patterns were identified to find key pathways driving the progression of lung adenocarcinoma. Furthermore, genomic alterations and differential expression analyses were performed to compare tumors with different radiological manifestations. Finally, a progressive index was developed to quantitatively measure the level of imbalance between tumor intrinsic growth potential and immune microenvironment. Results 12 patterns of gene expression were identified. Pathways associated with tumor growth and metastasis were found to be up-regulated as tumors progressed, while pathways associated with immune function were found to be down-regulated. Deconvolution of RNA-seq data also showed a decrease of CD8+ T cells and an increase of Tregs as the tumors progressed. Furthermore, tumors with more solid components on CT scan had a higher mutation frequency of tumor suppressor genes, higher tumor mutation burden and higher frequency of somatic copy number alterations. Finally, tumor progressive index demonstrated an increasing trend with the progression of lung adenocarcinoma. Discussion Imbalance of tumor intrinsic growth potential and immune function orchestrate the evolution of lung adenocarcinoma.

High-Grade Cervical Intraepithelial Neoplasia (CIN) Associates with Increased Proliferation and Attenuated Immune Signaling

Implementation of high-risk human papilloma virus (HPV) screening and the increasing proportion of HPV vaccinated women in the screening program will reduce the percentage of HPV positive women with oncogenic potential. In search of more specific markers to identify women with high risk of cancer development, we used RNA sequencing to compare the transcriptomic immune-profile of 13 lesions with cervical intraepithelial neoplasia grade 3 (CIN3) or adenocarcinoma in situ (AIS) and 14 normal biopsies from women with detected HPV infections. In CIN3/AIS lesions as compared to normal tissue, 27 differential expressed genes were identified. Transcriptomic analysis revealed significantly higher expression of a number of genes related to proliferation, (CDKN2A, MELK, CDK1, MKI67, CCNB2, BUB1, FOXM1, CDKN3), but significantly lower expression of genes related to a favorable immune response (NCAM1, ARG1, CD160, IL18, CX3CL1). Compared to the RNA sequencing results, good correlation was achieved with relative quantitative PCR analysis for NCAM1 and CDKN2A. Quantification of NCAM1 positive cells with immunohistochemistry showed epithelial reduction of NCAM1 in CIN3/AIS lesions. In conclusion, NCAM1 and CDKN2A are two promising candidates to distinguish whether women are at high risk of developing cervical cancer and in need of frequent follow-up.

Identification and Evaluation of Circulating Small Extracellular Vesicle Micrornas as Diagnostic Biomarkers for Patients with Indeterminate Pulmonary Nodules

Background: The identification of indeterminate pulmonary nodules (IPNs) following a low-dose computed tomography is a major challenge for early diagnosis of lung cancer. The inadequate assessment of IPNs’ malignancy risk results in a large number of unnecessary surgeries or an increased risk of cancer metastases. However, limited studies on non-invasive diagnosis of IPNs have been reported.Methods: In this study, we identified and evaluated the diagnostic value of circulating sEV miRNAs in patients with IPNs that had been newly detected using LDCT scanning and were scheduled for surgery. Out of 459 recruited patients, 109 eligible patients with IPNs were enrolled in the training cohort (n = 47) and the test cohort (n = 62). An external cohort (n=99) was used for validation. MiRNAs were extracted from plasma sEVs, and assessed using Small RNA sequencing. 490 lung adenocarcinoma samples and follow-up data were used to investigate the role of miRNAs in overall survival.Results: A circulating sEV miRNA (CirsEV-miR) model was constructed from five differentially expressed miRNAs (DEMs), showing 0.920 AUC in the training cohort (n = 47), and further identified in the test cohort (n = 62) and in an external validation cohort (n = 99). Among five DEMs of the CirsEV-miR model, miR-101-3p and miR-150-5p were significantly associated with better overall survival (p = 0.0001 and p = 0.0069). The CirsEV-miR scores were calculated, which significantly correlated with IPNs diameters (p < 0.05), and were able to discriminate between benign and malignant PNs (diameter ≤ 1 cm). The expression patterns of sEV miRNAs in the benign, adenocarcinoma in situ/minimally invasive adenocarcinoma, and invasive adenocarcinoma subgroups were found to gradually change with the increase in aggressiveness for the first time. Among all DEMs of the three subgroups, five miRNAs (miR-30c-5p, miR-30e-5p, miR-500a-3p, miR-125a-5p, and miR-99a-5p) were also significantly associated with overall survival of lung adenocarcinoma patients.Conclusions: Our results indicate that the CirsEV-miR model could help distinguish between benign and malignant PNs, providing insights into the feasibility of circulating sEV miRNAs in diagnostic biomarker development.Trial registration: Chinese Clinical Trials, ChiCTR1800019877. Registered 05 December 2018, https://www.chictr.org.cn/showproj.aspx?proj=31346.

Trafficking of Full-Length and N-Terminally Truncated Cathepsin B in Human Colorectal Carcinoma Cells

Cathepsin B is an endo-lysosomal cysteine protease. However, its increased expression and altered localization to the extracellular space, to mitochondria, or to the nucleus has been linked to tumor progression. In the present study, we show enhanced levels of cathepsin B in adenocarcinoma tissue in comparison to adjacent normal colon. Additionally, cathepsin B was observed in the nuclear compartment of mucosal cells in adenocarcinoma tissue samples and in the nuclei of the colorectal carcinoma cell line HCT116. Accordingly, a distinct 40-kDa form of cathepsin B was detected in HCT116 cells, which is proposed to represent a specific form lacking the signal peptide and parts of the propeptide. Trafficking studies with an EGFP-tagged N-terminally truncated form, mimicking the 40-kDa form, demonstrated accumulation in aggresome-like inclusion bodies, while EGFP-tagged full-length cathepsin B revealed regular sorting to endo-lysosomes. We conclude that the identity of nuclear cathepsin B in colorectal adenocarcinoma (in situ) and in carcinoma cells (in vitro) cannot be attributed to either full-length or 40-kDa N-terminally truncated cathepsin B forms. Hence, future studies are needed to demonstrate which form/s of cathepsin B may be sorted to the nuclei of colorectal carcinoma cells, and whether redundant regulation of related cathepsin expression occurs.

Spectrum of Histopathological Lesions in Cholecystectomy Specimens at Pak Red Crescent Teaching Hospital

Objective: To study the spectrum of histopathological lesions found on surgically resected gallbladder to quantify the various abnormalities in gallbladder specimen. Methodology: A descriptive observational study was carried out from Nov 2017 to Oct 2021. All the patients undergoing emergency and elective cholecystectomy regardless of age and sex were included in the study. After cholecystectomy, gallbladder specimen along with history and ultrasound findings was sent for histopathology to our own institution. Department of histopathology has the standardized method to process the gallbladder specimens. Demographic data along with diagnosis, ultrasound finding and histopathology report were collected and analyzed with Excel 2019. Results: Total number of patients in this study was 395, out of which 93 patients were male and 302 patients were female. Average age of our patients was 43.05± 13 years. Acute calculus cholecystitis was found in 55 (13.92%) patients, 298 (75.44) patents had chronic calculus cholecystitis, empyema was found in 15 (3.80) patients, cholestrolosis was found in 5 (1.27%) patients, gallbladder polyp was found in 02 (0.51%) patients, gangrenous gall bladder was found in 01 (0.25%) patient and adenocarcinoma in situ was found in 01 (0.25%) patient. Conclusion: Our study shows that, chronic cholecystitis is the most common presentation followed by acute cholecystitis in surgically resected gallbladders. Females are predominantly suffering from the gallbladder diseases. The frequency of malignant lesion was very low. Keywords: Gallbladder-histopathology, Acute Cholecystitis, Chronic Cholecystitis, Gallstones.

Adenocarcinoma in situ and minimally invasive adenocarcinoma in lungs of smokers: image feature differences from those in lungs of non-smokers

Purpose We aimed to examine the characteristics of imaging findings of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) in the lungs of smokers compared with those of non-smokers. Materials and methods We included seven cases of AIS and 20 cases of MIA in lungs of smokers (pack-years ≥ 20) and the same number of cases of AIS and MIA in lungs of non-smokers (pack-years = 0). We compared the diameter of the entire lesion and solid component measured on computed tomography (CT) images, pathological size and invasive component diameter measured from pathological specimens, and CT values of the entire lesion and ground-glass opacity (GGO) portions between the smoker and non-smoker groups. Results The diameters of AIS and MIA on CT images and pathological specimens of the smoker group were significantly larger than those of the non-smoker group (p = 0.036 and 0.008, respectively), whereas there was no significant difference in the diameter of the solid component on CT images or invasive component of pathological specimens between the two groups. Additionally, mean CT values of the entire lesion and GGO component of the lesions in the smoker group were significantly lower than those in the non-smoker group (p = 0.036 and 0.040, respectively). Conclusion AIS and MIA in smoker’s lung tended to have larger lesion diameter and lower internal CT values compared with lesions in non-smoker’s lung. This study calls an attention on smoking status in CT-based diagnosis for early stage adenocarcinoma.