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Journal of Pharmacy & Bioallied Sciences Apr 2024histopathology plays a pivotal role in clinical diagnosis, research, and medical education. In recent years, whole slide imaging (wsi) has emerged as a potential...
BACKGROUND
histopathology plays a pivotal role in clinical diagnosis, research, and medical education. In recent years, whole slide imaging (wsi) has emerged as a potential alternative to traditional microscopy for pathological examination. This study aims to provide a comprehensive comparison of wsi and traditional microscopy(tm) in various aspects of histopathology practice.
MATERIALS AND METHODS
In this study, total of 30 cases comprising of oral premalignant and malignant cases which were diagnostically challenging was considered from the archives of the institute for validation. The slides were scanned with slide scanner and were evaluated by histopathologists. The comparative parameters which were noted were diagnostic discordances, number of fields observed to reach the diagnosis and time taken.
RESULTS
The mean time taken by the pathologists to reach the diagnosis was significantly less in whole slide imaging technique. The average number of fields observed was higher by using wsi that too in a lesser time compared to tm, the results were found to be statistically significant with p=0.001.however the diagnostic disparity were seen to be maximum for verrucous lesions both in wsi and tm.
CONCLUSION
wsi has facilitated the specialty with rapid mode of diagnosis in a more efficient and error less manner. It has also aided in case banking as well as research possibilities. Hence with the advent of telepathology it is very much necessary to get trained with wsi as early as possible so that the professionals can render correct diagnosis.
PubMed: 38882897
DOI: 10.4103/jpbs.jpbs_1042_23 -
Journal of Pharmacy & Bioallied Sciences Apr 2024Oral malignant lesions are the most common malignancy of which majority are diagnosed in advanced stages in Saudi Arabia. Patients with oral malignant lesion are first...
Oral malignant lesions are the most common malignancy of which majority are diagnosed in advanced stages in Saudi Arabia. Patients with oral malignant lesion are first seen by general dental practitioners and dental students. Multiple surveys have been conducted and published to assess the students, interns, and dentists' awareness and attitude toward oral premalignant lesions worldwide. However, little is known about this issue in Saudi Arabia. We aimed to assess knowledge and awareness of detecting oral premalignant lesions among dental students, dental interns, and practitioners in Saudi Arabia. A cross-sectional questionnaire-based survey was conducted and electronically distributed. The questionnaire comprised of three sections including demographic variables, knowledge of risk factors of oral malignancy, and six clinical case scenarios. Descriptive statistics were used, and the results were reported using cross-tabulation and the Chi-square test. A 300 participants answered to the questionnaire, and 83% of respondents strongly agreed that smoking is a risk factor for oral malignancy. However, there was some uncertainty in responses for some more specific oral-related factors, such as a sharp-edged tooth and irritation from dental restoration. Furthermore, the knowledge and awareness of detecting frankly benign and frankly malignant lesions such as fibroma and squamous cell carcinoma are higher comparing to potentially malignant lesion, i.e. lichen planus. Knowledge and awareness of detecting oral premalignant lesions vary based on malignancy factors and by participants academic level. Fibroma and SCC are detected easily among all participants. However, lichen planus was the hardest to diagnose among oral lesions.
PubMed: 38882888
DOI: 10.4103/jpbs.jpbs_895_23 -
Nature Communications Jun 2024The growing scale and dimensionality of multiplexed imaging require reproducible and comprehensive yet user-friendly computational pipelines. TRACERx-PHLEX performs deep...
The growing scale and dimensionality of multiplexed imaging require reproducible and comprehensive yet user-friendly computational pipelines. TRACERx-PHLEX performs deep learning-based cell segmentation (deep-imcyto), automated cell-type annotation (TYPEx) and interpretable spatial analysis (Spatial-PHLEX) as three independent but interoperable modules. PHLEX generates single-cell identities, cell densities within tissue compartments, marker positivity calls and spatial metrics such as cellular barrier scores, along with summary graphs and spatial visualisations. PHLEX was developed using imaging mass cytometry (IMC) in the TRACERx study, validated using published Co-detection by indexing (CODEX), IMC and orthogonal data and benchmarked against state-of-the-art approaches. We evaluated its use on different tissue types, tissue fixation conditions, image sizes and antibody panels. As PHLEX is an automated and containerised Nextflow pipeline, manual assessment, programming skills or pathology expertise are not essential. PHLEX offers an end-to-end solution in a growing field of highly multiplexed data and provides clinically relevant insights.
Topics: Humans; Deep Learning; Image Processing, Computer-Assisted; Animals; Software; Spatial Analysis; Single-Cell Analysis; Phenotype; Mice; Image Cytometry
PubMed: 38879602
DOI: 10.1038/s41467-024-48870-5 -
Biomolecules & Biomedicine May 2024The development of cervical and vaginal intraepithelial neoplasias (CIN and VaIN) is strongly associated with human papillomavirus (HPV) infections, representing key...
The development of cervical and vaginal intraepithelial neoplasias (CIN and VaIN) is strongly associated with human papillomavirus (HPV) infections, representing key precancerous conditions in women. This study investigates the influence of different cervical treatment methods on the rate of subsequent vaginal neoplasia. It also considers age and menopausal status as risk factors for higher-grade VaIN and the role of persistent HPV infections in the development of new VaIN cases post-treatment. The cohort consisted of 275 female patients treated for CIN, with a follow-up period of six months including HPV and ThinPrep cytologic test (TCT) testing. The evaluated treatments included laser therapy, cervical conization, loop electrosurgical excision procedure (LEEP), and radical hysterectomy. Statistical analysis was performed using SPSS 26.0 to determine treatment efficacy, the impact of age and menopausal status, and the relationship between HPV clearance and VaIN outcomes. Radical hysterectomy was linked with a higher recurrence of VaIN. Additionally, patients over 50 years old and those who were postmenopausal were significantly more likely to develop more severe VaIN and persistent HPV infections. Persistence of HPV after treatment was linked to a higher incidence of new VaIN cases. High-risk HPV significantly increased the recurrence of VaIN, with no significant link found between TCT results and VaIN severity. Therefore, selecting appropriate cervical lesion treatment, considering the patient's age and menopausal status, and managing HPV infections are essential in preventing and managing the risk and progression of VaIN. Radical hysterectomy showed a distinct increase in VaIN incidence, emphasizing the need for individualized clinical assessments.
PubMed: 38878306
DOI: 10.17305/bb.2024.10523 -
Archives of Dermatological Research Jun 2024Clinical grading of actinic keratosis (AK) is based on skin surface features, while subclinical alterations are not taken into consideration. Dynamic optical coherence...
Clinical grading of actinic keratosis (AK) is based on skin surface features, while subclinical alterations are not taken into consideration. Dynamic optical coherence tomography (D-OCT) enables quantification of the skin´s vasculature, potentially helpful to improve the link between clinical and subclinical features. We aimed to compare microvascular characteristics across AK grades using D-OCT with automated vascular analysis. This explorative study examined AK and photodamaged skin (PD) on the face or scalp. AKs were clinically graded according to the Olsen Classification scheme before D-OCT assessment. Using an open-source software tool, the OCT angiographic analyzer (OCTAVA), we quantified vascular network features, including total and mean vessel length, mean vessel diameter, vessel area density (VAD), branchpoint density (BD), and mean tortuosity from enface maximum intensity projection images. Additionally, we performed subregional analyses on selected scans to overcome challenges associated with imaging through hyperkeratosis (each lesion group; n = 18). Our study included 45 patients with a total of 205 AKs; 93 grade I lesions, 65 grade II, 47 grade III and 89 areas with PD skin. We found that all AK grades were more extensively vascularized relative to PD, as shown by greater total vessel length and VAD (p ≤ 0.009). Moreover, AKs displayed a disorganized vascular network, with higher BD in AK I-II (p < 0.001), and mean tortuosity in AK II-III (p ≤ 0.001) than in PD. Vascularization also increased with AK grade, showing significantly greater total vessel length in AK III than AK I (p = 0.029). Microvascular quantification of AK unveiled subclinical, quantitative differences among AK grades I-III and PD skin. D-OCT-based microvascular assessment may serve as a supplement to clinical AK grading, potentially raising perspectives to improve management strategies.
Topics: Humans; Tomography, Optical Coherence; Keratosis, Actinic; Male; Female; Aged; Middle Aged; Skin; Severity of Illness Index; Aged, 80 and over; Scalp; Skin Aging; Face
PubMed: 38878217
DOI: 10.1007/s00403-024-03022-z -
Cancer Medicine Jun 2024Visual inspection with acetic acid (VIA) is a low-cost approach for cervical cancer screening used in most low- and middle-income countries (LMICs) but, similar to other...
OBJECTIVES
Visual inspection with acetic acid (VIA) is a low-cost approach for cervical cancer screening used in most low- and middle-income countries (LMICs) but, similar to other visual tests, is subjective and requires sustained training and quality assurance. We developed, trained, and validated an artificial-intelligence-based "Automated Visual Evaluation" (AVE) tool that can be adapted to run on smartphones to assess smartphone-captured images of the cervix and identify precancerous lesions, helping augment VIA performance.
DESIGN
Prospective study.
SETTING
Eight public health facilities in Zambia.
PARTICIPANTS
A total of 8204 women aged 25-55.
INTERVENTIONS
Cervical images captured on commonly used low-cost smartphone models were matched with key clinical information including human immunodeficiency virus (HIV) and human papillomavirus (HPV) status, plus histopathology analysis (where applicable), to develop and train an AVE algorithm and evaluate its performance for use as a primary screen and triage test for women who are HPV positive.
MAIN OUTCOME MEASURES
Area under the receiver operating curve (AUC); sensitivity; specificity.
RESULTS
As a general population screening tool for cervical precancerous lesions, AVE identified cases of cervical precancerous and cancerous (CIN2+) lesions with high performance (AUC = 0.91, 95% confidence interval [CI] = 0.89-0.93), which translates to a sensitivity of 85% (95% CI = 81%-90%) and specificity of 86% (95% CI = 84%-88%) based on maximizing the Youden's index. This represents a considerable improvement over naked eye VIA, which as per a meta-analysis by the World Health Organization (WHO) has a sensitivity of 66% and specificity of 87%. For women living with HIV, the AUC of AVE was 0.91 (95% CI = 0.88-0.93), and among those testing positive for high-risk HPV types, the AUC was 0.87 (95% CI = 0.83-0.91).
CONCLUSIONS
These results demonstrate the feasibility of utilizing AVE on images captured using a commonly available smartphone by nurses in a screening program, and support our ongoing efforts for moving to more broadly evaluate AVE for its clinical sensitivity, specificity, feasibility, and acceptability across a wider range of settings. Limitations of this study include potential inflation of performance estimates due to verification bias (as biopsies were only obtained from participants with visible aceto-white cervical lesions) and due to this being an internal validation (the test data, while independent from that used to develop the algorithm was drawn from the same study).
Topics: Humans; Female; Uterine Cervical Neoplasms; Smartphone; Zambia; Adult; Early Detection of Cancer; Prospective Studies; Middle Aged; Sensitivity and Specificity; Papillomavirus Infections; Algorithms; Uterine Cervical Dysplasia; Mass Screening; ROC Curve; Artificial Intelligence
PubMed: 38872398
DOI: 10.1002/cam4.7355 -
Cancer Medicine Jun 2024The genomic and molecular ecology involved in the stepwise continuum progression of lung adenocarcinoma (LUAD) from adenocarcinoma in situ (AIS) to minimally invasive...
Integrated whole-exome and bulk transcriptome sequencing delineates the dynamic evolution from preneoplasia to invasive lung adenocarcinoma featured with ground-glass nodules.
OBJECTIVE
The genomic and molecular ecology involved in the stepwise continuum progression of lung adenocarcinoma (LUAD) from adenocarcinoma in situ (AIS) to minimally invasive adenocarcinoma (MIA) and subsequent invasive adenocarcinoma (IAC) remains unclear and requires further elucidation. We aimed to characterize gene mutations and expression landscapes, and explore the association between differentially expressed genes (DEGs) and significantly mutated genes (SMGs) during the dynamic evolution from AIS to IAC.
METHODS
Thirty-five patients with ground-glass nodules (GGNs) lung adenocarcinomas were enrolled. Whole-exome sequencing (WES) and transcriptome sequencing (RNA-Seq) were conducted on all patients, encompassing both tumor samples and corresponding noncancerous tissues. Data obtained from WES and RNA-Seq were subsequently analyzed.
RESULTS
The findings from WES delineated that the predominant mutations were observed in EGFR (49%) and ANKRD36C (17%). SMGs, including EGFR and RBM10, were associated with the dynamic evolution from AIS to IAC. Meanwhile, DEGs, including GPR143, CCR9, ADAMTS16, and others were associated with the entire process of invasive LUAD. We found that the signaling pathways related to cell migration and invasion were upregulated, and the signaling pathways of angiogenesis were downregulated across the pathological stages. Furthermore, we found that the messenger RNA (mRNA) levels of FAM83A, MAL2, DEPTOR, and others were significantly correlated with CNVs. Gene set enrichment analysis (GSEA) showed that heme metabolism and cholesterol homeostasis pathways were significantly upregulated in patients with EGFR/RBM10 co-mutations, and these patients may have poorer overall survival than those with EGFR mutations. Based on the six calculation methods for the immune infiltration score, NK/CD8 T cells decreased, and Treg/B cells increased with the progression of early LUAD.
CONCLUSIONS
Our findings offer valuable insights into the unique genomic and molecular features of LUAD, facilitating the identification and advancement of precision medicine strategies targeting the invasive progression of LUAD from AIS to IAC.
Topics: Humans; Exome Sequencing; Adenocarcinoma of Lung; Lung Neoplasms; Male; Female; Mutation; Middle Aged; Aged; Neoplasm Invasiveness; Disease Progression; Gene Expression Regulation, Neoplastic; Transcriptome; Gene Expression Profiling; Adenocarcinoma in Situ; Precancerous Conditions; Biomarkers, Tumor
PubMed: 38864483
DOI: 10.1002/cam4.7383 -
Iranian Journal of Pathology 2024Penile squamous cell carcinoma (SCC) is an extremely rare malignancy. It is usually caused by chronic human papillomavirus (HPV) 16 and HPV 18 infections. This study was...
BACKGROUND & OBJECTIVE
Penile squamous cell carcinoma (SCC) is an extremely rare malignancy. It is usually caused by chronic human papillomavirus (HPV) 16 and HPV 18 infections. This study was conducted to investigate the immunohistochemical overexpression of p16, a surrogate marker for HPV, and to evaluate its usefulness as a potential diagnostic biomarker.
METHODS
In this cross-sectional prospective and retrospective cohort study, 56 penile squamous cell carcinoma (SCC) specimens and five penile premalignant specimens were evaluated in Kasturba Medical College, Mangalore, India, from January 2013- December 2018 in terms of clinical and histopathological features. Immunohistochemical expression for p16 in cases and controls was evaluated. Statistical comparison of p16 expression among clinical features, histological subtype, grade, and stages of tumor were done.
RESULTS
Analysis of the pattern of p16 staining showed diffuse and strong nuclear and cytoplasmic expression in 32.8% of the cases. There was a highly significant association (<0.001) of pattern of p16 expression among the HPV and non-HPV subtypes of penile carcinoma. p16 expression was not significantly associated with other prognostic parameters like site of the lesion, lymphovascular invasion, perineural invasion, histologic grade, and pathologic stage.
CONCLUSION
Expression of p16 would be a useful tool in differentiation between the HPV-associated and non-HPV-associated subtypes of penile SCC that may be helpful in prediction of aggressiveness and invasive potential of the respective histologic subtypes.
PubMed: 38864076
DOI: 10.30699/IJP.2024.1998898.3092 -
Clinical Epigenetics Jun 2024The major challenge in routine endocervical curettage (ECC) among Human Papillomavirus (HPV) 16/18-positive patients is that only a small fraction benefit. Nevertheless,...
PAX1 methylation as a robust predictor: developing and validating a nomogram for assessing endocervical curettage (ECC) necessity in human papillomavirus16/18-positive women undergoing colposcopy.
OBJECTIVE
The major challenge in routine endocervical curettage (ECC) among Human Papillomavirus (HPV) 16/18-positive patients is that only a small fraction benefit. Nevertheless, current reported models often overestimate the validity and necessity of ECC, making it difficult to improve benefits for patients. This research hypothesized that assessing paired boxed gene 1 methylation levels (PAX1) and clinical characteristics could enhance the predictive accuracy of detecting additional high-grade squamous intraepithelial lesions or worse (HSIL +) through ECC that were not identified by colposcopy-directed biopsy (CDB).
METHODS
Data from 134 women with HPV16/18 positivity undergoing CDB and ECC between April 2018 and April 2022 were collected and analyzed. Quantitative methylation-specific polymerase chain reaction (qMSP) was utilized to measure PAX1, expressed as ΔCp. Univariate and multivariate regression analyses were conducted to screen variables and select predictive factors. A nomogram was constructed using multivariate logistic regression to predict additional HSIL + detected by ECC. The discrimination, calibration, and clinical utility of the nomogram were evaluated using receiver operating characteristic curves (ROC) and the calibration plot.
RESULTS
Age (odds ratio [OR], 5.654; 95% confidence interval [CI], 1.131-37.700), cytology (OR, 24.978; 95% CI, 3.085-540.236), and PAX1 methylation levels by grade (PAX1 grade) (OR, 7.801; 95% CI, 1.548-44.828) were independent predictive factors for additional detection of HSIL + by ECC. In HPV16/18-positive women, the likelihood of additional detection of HSIL + through ECC increased with the severity of cytological abnormalities, peaking at 43.8% for high-grade cytological lesions. Moreover, when cytological findings indicated low-grade lesions, PAX1 methylation levels were positively correlated with the additional detection of HSIL + by ECC (P value < 0.001). A nomogram prediction model was developed (area under curve (AUC) = 0.946; 95% CI, 0.901-0.991), demonstrating high sensitivity (90.9%) and specificity (90.5%) at the optimal cutoff point of 107. Calibration analysis confirmed the model's strong agreement between predicted and observed probabilities.
CONCLUSION
The clinical nomogram presented promising predictive performance for the additional detection of HSIL + through ECC among women with HPV16/18 infection. PAX1 methylation level could serve as a valuable tool in guiding individualized clinical decisions regarding ECC for patients with HPV 16/18 infection, particularly in cases of low-grade cytological findings.
Topics: Humans; Female; Paired Box Transcription Factors; Human papillomavirus 16; Nomograms; Adult; DNA Methylation; Middle Aged; Human papillomavirus 18; Papillomavirus Infections; Colposcopy; Uterine Cervical Neoplasms; Curettage; ROC Curve; Uterine Cervical Dysplasia; Cervix Uteri
PubMed: 38849868
DOI: 10.1186/s13148-024-01691-1 -
BMC Women's Health Jun 2024This study aims to analyze factors associated with positive surgical margins following cold knife conization (CKC) in patients with cervical high-grade squamous...
Development of a machine learning-based model for predicting positive margins in high-grade squamous intraepithelial lesion (HSIL) treatment by Cold Knife Conization(CKC): a single-center retrospective study.
OBJECTIVES
This study aims to analyze factors associated with positive surgical margins following cold knife conization (CKC) in patients with cervical high-grade squamous intraepithelial lesion (HSIL) and to develop a machine-learning-based risk prediction model.
METHOD
We conducted a retrospective analysis of 3,343 patients who underwent CKC for HSIL at our institution. Logistic regression was employed to examine the relationship between demographic and pathological characteristics and the occurrence of positive surgical margins. Various machine learning methods were then applied to construct and evaluate the performance of the risk prediction model.
RESULTS
The overall rate of positive surgical margins was 12.9%. Independent risk factors identified included glandular involvement (OR = 1.716, 95% CI: 1.345-2.189), transformation zone III (OR = 2.838, 95% CI: 2.258-3.568), HPV16/18 infection (OR = 2.863, 95% CI: 2.247-3.648), multiple HR-HPV infections (OR = 1.930, 95% CI: 1.537-2.425), TCT ≥ ASC-H (OR = 3.251, 95% CI: 2.584-4.091), and lesions covering ≥ 3 quadrants (OR = 3.264, 95% CI: 2.593-4.110). Logistic regression demonstrated the best prediction performance, with an accuracy of 74.7%, sensitivity of 76.7%, specificity of 74.4%, and AUC of 0.826.
CONCLUSION
Independent risk factors for positive margins after CKC include HPV16/18 infection, multiple HR-HPV infections, glandular involvement, extensive lesion coverage, high TCT grades, and involvement of transformation zone III. The logistic regression model provides a robust and clinically valuable tool for predicting the risk of positive margins, guiding clinical decisions and patient management post-CKC.
Topics: Humans; Female; Retrospective Studies; Machine Learning; Adult; Margins of Excision; Conization; Middle Aged; Uterine Cervical Neoplasms; Squamous Intraepithelial Lesions; Risk Factors; Squamous Intraepithelial Lesions of the Cervix; Uterine Cervical Dysplasia; Papillomavirus Infections; Aged; Logistic Models; Cryosurgery; Young Adult
PubMed: 38849836
DOI: 10.1186/s12905-024-03180-2