HPV DNA Testing and Mobile Colposcopy for Cervical Precancer Screening in HIV Positive Women: A Comparison Between Two Settings in Ghana and Recommendation for Screening.

INTRODUCTION: Women living with HIV (WLHIV) have higher prevalence and persistence rates of high-risk human papillomavirus (hr-HPV) infection with a six-fold increased risk of cervical cancer. Thus, more frequent screening is recommended for WLHIV. OBJECTIVES: This retrospective descriptive cross-sectional study was conducted to investigate and compare the prevalence of hr-HPV infection and abnormal findings on mobile colposcopy in two cohorts of WLHIV following cervical screening in rural and urban settings in Ghana. METHODS: Through the mPharma 10 000 Women Initiative, WLHIV were screened via concurrent hr-HPV DNA testing (MA-6000; Sansure Biotech Inc., Hunan, China) and visual inspection (Enhanced Visual Assessment [EVA] mobile colposcope; MobileODT, Tel Aviv, Israel) by trained nurses. The women were screened while undergoing routine outpatient reviews at HIV clinics held at the Catholic Hospital, Battor (rural setting) and Tema General Hospital (urban setting), both in Ghana. RESULTS: Two-hundred and fifty-eight WLHIV were included in the analysis (rural, n = 132; urban, n = 126). The two groups were comparable in terms of age, time since HIV diagnosis, and duration of treatment for HIV. The hr-HPV prevalence rates were 53.7% (95% CI, 45.3-62.3) and 48.4% (95% CI, 39.7-57.1) among WLHIV screened in the rural vs urban settings (p-value = .388). Abnormal colposcopy findings were found in 8.5% (95% CI, 5.1-11.9) of the WLHIV, with no significant difference in detection rates between the two settings (p-value = .221). Three (13.6%) of 22 women who showed abnormal colposcopic findings underwent loop electrosurgical excision procedure (LEEP), leaving 19/22 women from both rural and urban areas with pending treatment/follow-up results, which demonstrates the difficulty faced in reaching early diagnosis and treatment, regardless of their area of residence. Histopathology following LEEP revealed CIN III in 2 WLHIV (urban setting, both hr-HPV negative) and CIN I in 1 woman in the rural setting (hr-HPV positive). CONCLUSIONS: There is a high prevalence of hr-HPV among WLHIV in both rural and urban settings in this study in Ghana. Concurrent HPV DNA testing with a visual inspection method (colposcopy/VIA) reduces loss to follow-up compared to performing HPV DNA testing as a standalone test and recalling hr-HPV positive women for follow up with a visual inspection method. Concurrent HPV DNA testing and a visual inspection method may also pick up precancerous cervical lesions that are hr-HPV negative and may be missed if HPV DNA testing is performed alone.

The Hallmarks of Precancer.

Research on precancers, as defined as at-risk tissues and early lesions, is of high significance given the effectiveness of early intervention. We discuss the need for risk stratification to prevent overtreatment, an emphasis on the role of genetic and epigenetic aging when considering risk, and the importance of integrating macroenvironmental risk factors with molecules and cells in lesions and at-risk normal tissues for developing effective intervention and health policy strategies.

Colorectal cancer initiation: Understanding early-stage disease for intervention.

How tumors arise or the cause of precancerous lesions is a fundamental question in cancer biology. It is generally accepted that tumors originate from normal cells that undergo uncontrolled proliferation owing to genetic alterations. At the onset of adenoma formation, cancer driver mutations confer clonal growth advantage, enabling mutant cells to outcompete and eliminate the surrounding healthy cells. Hence, the development of precancerous lesions is not only attributed to the expansion of pre-malignant clones, but also relies on the relative fitness of mutated cells compared to the neighboring cells. Colorectal cancer (CRC) is an excellent model to investigate cancer origin as it follows a stereotypical process from mutant cell hyperplasia to adenoma formation and progression. Here, we review the evolving understanding of colonic tumor development, focusing on how cell intrinsic and extrinsic factors impact cell competition and the "clone war" between cancer-initiating cells and normal stem cells. We also discuss the promises and limitations of targeting cell competitiveness in cancer prevention and early intervention. The field of tumor initiation is currently in its infancy, elucidating the adenoma origin is crucial for designing effective prevention strategies and early treatments before cancer becomes incurable.

miR-129-5p inhibits anchorage-independent growth through silencing of ACTN1 and the ELK4/c-FOS axis in HPV-transformed keratinocytes.

A persistent infection with human papillomavirus (HPV) can induce precancerous lesions of the cervix that may ultimately develop into cancer. Cervical cancer development has been linked to altered microRNA (miRNA) expression, with miRNAs regulating anchorage-independent growth being particularly important for the progression of precancerous lesions to cancer. In this study, we set out to identify and validate targets of miR-129-5p, a previously identified tumor suppressive miRNA involved in anchorage-independent growth and HPV-induced carcinogenesis. We predicted 26 potential miR-129-5p targets using online databases, followed by KEGG pathway enrichment analysis. RT-qPCR and luciferase assays confirmed that 3'UTR regions of six genes (ACTN1, BMPR2, CAMK4, ELK4, EP300, and GNAQ) were targeted by miR-129-5p. Expressions of ACTN1, CAMK4, and ELK4 were inversely correlated to miR-129-5p expression in HPV-transformed keratinocytes, and their silencing reduced anchorage-independent growth. Concordantly, miR-129-5p overexpression decreased protein levels of ACTN1, BMPR2, CAMK4 and ELK4 in anchorage-independent conditions. Additionally, c-FOS, a downstream target of ELK4, was downregulated upon miR-129-5p overexpression, suggesting regulation through the ELK4/c-FOS axis. ACTN1 and ELK4 expression was also upregulated in high-grade precancerous lesions and cervical cancers, supporting their clinical relevance. In conclusion, we identified six targets of miR-129-5p involved in the regulation of anchorage-independent growth, with ACTN1, BMPR2, ELK4, EP300, and GNAQ representing novel targets for miR-129-5p. For both ACTN1 and ELK4 functional and clinical relevance was confirmed, indicating that miR-129-5p-regulated ACTN1 and ELK4 expression contributes to HPV-induced carcinogenesis.

Stool Glycoproteomics Signatures of Pre-Cancerous Lesions and Colorectal Cancer.

Colorectal cancer (CRC) screening relies primarily on stool analysis to identify occult blood. However, its sensitivity for detecting precancerous lesions is limited, requiring the development of new tools to improve CRC screening. Carcinogenesis involves significant alterations in mucosal epithelium glycocalyx that decisively contribute to disease progression. Building on this knowledge, we examined patient series comprehending premalignant lesions, colorectal tumors, and healthy controls for the T-antigen-a short-chain O-glycosylation of proteins considered a surrogate marker of malignancy in multiple solid cancers. We found the T-antigen in the secretions of dysplastic lesions as well as in cancer. In CRC, T-antigen expression was associated with the presence of distant metastases. In parallel, we analyzed a broad number of stools from individuals who underwent colonoscopy, which showed high T expressions in high-grade dysplasia and carcinomas. Employing mass spectrometry-based lectin-affinity enrichment, we identified a total of 262 proteins, 67% of which potentially exhibited altered glycosylation patterns associated with cancer and advanced pre-cancerous lesions. Also, we found that the stool (glyco)proteome of pre-cancerous lesions is enriched for protein species involved in key biological processes linked to humoral and innate immune responses. This study offers a thorough analysis of the stool glycoproteome, laying the groundwork for harnessing glycosylation alterations to improve non-invasive cancer detection.

Inhibiting Pathological Calcium Phosphate Mineralization: Implications for Disease Progression.

Pathological calcifications, especially calcium phosphate microcalcifications (MCs), appear in most early breast cancer lesions, and their formation correlates with more aggressive tumors and a poorer prognosis. Hydroxyapatite (HA) is a key MC component that crystallizes in the tumor microenvironment. It is often associated with malignant breast cancer lesions and can trigger tumorigenesis in vitro. Here, we investigate the impact of additives on HA crystallization and inhibition, and how precancerous breast cells respond to minerals that are deposited in the presence of these additives. We show that nonstoichiometric HA spontaneously crystallizes in a solution simulating the tumor microenvironmental fluids and exhibits lump-like morphology similar to breast cancer MCs. In this system, the effectiveness of poly(aspartic acid) and poly(acrylic acid) (PAA) to inhibit HA is examined as a potential route to improve cancer prognosis. In the presence of additives, the formation of HA lumps is associated with the promotion or only minimal inhibition of mineralization, whereas the formation of amorphous calcium phosphate (ACP) lumps is followed by inhibition of mineralization. PAA emerges as a robust HA inhibitor by forming spherical ACP particles. When precancerous breast cells are exposed to various HA and ACP minerals, the most influential factors on cell proliferation are the mineral phase and whether the mineral is in the form of discrete particles or particle aggregates. The tumorigenic effects on cells, ranging from cytotoxicity and suppression of proliferation to triggering of proliferation, can be summarized as HA particles < HA aggregates < ACP particles < ACP aggregates. The cellular response to minerals can be attributed to a combination of factors, including mineral phase, crystallinity, morphology, surface texture, aggregation state, and surface potential. These findings have implications for understanding mineral-cell interactions within the tumor microenvironment and suggest that, in some cases, the byproducts of HA inhibition can contribute to disease progression more than HA itself.

Deep learning assists detection of esophageal cancer and precursor lesions in a prospective, randomized controlled study.

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.

Blood-Based Multiomics-Guided Detection of a Precancerous Pancreatic Tumor.

Over a decade ago, longitudinal multiomics analysis was pioneered for early disease detection and individually tailored precision health interventions. However, high sample processing costs, expansive multiomics measurements along with complex data analysis have made this approach to precision/personalized medicine impractical. Here we describe in a case report, a more practical approach that uses fewer measurements, annual sampling, and faster decision making. We also show how this approach offers promise to detect an exceedingly rare and potentially fatal condition before it fully manifests. Specifically, we describe in the present case report how longitudinal multiomics monitoring (LMOM) helped detect a precancerous pancreatic tumor and led to a successful surgical intervention. The patient, enrolled in an annual blood-based LMOM since 2018, had dramatic changes in the June 2021 and 2022 annual metabolomics and proteomics results that prompted further clinical diagnostic testing for pancreatic cancer. Using abdominal magnetic resonance imaging, a 2.6 cm lesion in the tail of the patient's pancreas was detected. The tumor fluid from an aspiration biopsy had 10,000 times that of normal carcinoembryonic antigen levels. After the tumor was surgically resected, histopathological findings confirmed it was a precancerous pancreatic tumor. Postoperative omics testing indicated that most metabolite and protein levels returned to patient's 2018 levels. This case report illustrates the potentials of blood LMOM for precision/personalized medicine, and new ways of thinking medical innovation for a potentially life-saving early diagnosis of pancreatic cancer. Blood LMOM warrants future programmatic translational research with the goals of precision medicine, and individually tailored cancer diagnoses and treatments.

Histopathologic patterns and factors associated with cervical lesions at Jimma Medical Center, Jimma, Southwest Ethiopia: A two-year cross-sectional study.

BACKGROUND: The cervix is the lower portion of the uterus, which connects this organ to the vagina through the endocervical canal. OBJECTIVE: This study aimed to determine the histopathologic patterns and factors associated with cervical lesions at Jimma Medical Center from September 12, 2017, to September 12, 2019. METHODS: A 2-year facility-based cross-sectional study was conducted from May 1 to June 30, 2020. RESULT: In this study, cervical cancer was the most common (71%) cause of cervical lesions. Squamous cell carcinoma was the most frequent cervical cancer diagnosed during the study, accounting for 96.4% of 331 cancerous cases, followed by adenocarcinoma (3.3%). High-grade squamous intraepithelial lesions were the most frequently diagnosed precancerous lesions, accounting for 68.4% of cases. Endocervical polyps were the most commonly diagnosed benign lesions, accounting for 59.3% of cases. CONCLUSION: The maximum age distribution of cervical lesions was in the 41-50-year age range. Squamous cell carcinoma was the most frequent type of cervical cancer. High-grade squamous intraepithelial lesions were the most frequently diagnosed precancerous cervical lesions. The most common benign cervical lesions were endocervical polyps. RECOMMENDATION: We recommend educating the community to improve health-seeking behavior and on possible preventive strategies for cervical cancer.

Cervical precancerous and cancerous lesions screening using Pap smear test at Provincial Referral Hospital of Bukavu, Eastern DR Congo: profile and recommendations to stakeholders.

Introduction: cervical cancer is a health concern worldwide. The South Kivu Province in the Eastern DR Congo is facing many cases of this disease but poorly screened and reported. The objective of this was to determine the prevalence of cell abnormalities at cervical cytology in a tertiary teaching hospital in Bukavu and their association with common risk factors of cervical cancer. Methods: a cross-sectional study was conducted on 142 women attending the Provincial Referral Hospital of Bukavu (HPGRB) from February to December 2021. Quantitative variables were described by their median following their asymmetric distributions and the qualitative variables in absolute and relative frequencies. Then the Chi-square test was used for the comparison of proportion. Results: forty-five percent of the participants had between three and five children. Twenty-two (15.5%) of the 142 patients reported to have two or more sexual partners and 17.5% reported the use of hormonal contraception. The prevalence of cell abnormalities at cervical cytology was 17% of which Low- Grade Squamous Intraepithelial Lesion (LSIL) was the most representative (12.9%). There was no statistically significant association between the common cervical risk factors and the occurrence of cell abnormalities. Conclusion: cervical pre-cancerous lesions are frequent in South Kivu province. The Pap smear test remains an early and affordable screening method and constitutes a secondary prevention strategy in women of 18 years and older in a low-income country such as DR Congo where vaccination against HPV is still hypothetic.

The role of fine-needle aspiration biopsy in the diagnosis of malignant tumors.

Cytopathology and histopathology play a key role in the process of diagnosing oncological diseases and premalignant conditions. Fine-needle aspiration (FNA) is one of the techniques used for obtaining biopsy of a wide variety of body tissues, causing patients minimal discomfort. Therefore, it is often considered to be the best strategy for investigating and diagnosing some precancerous or potential malignant lesions. Being successful as a means of confirming the clinical suspicion of metastatic recurrence in the cases of an already known cancer, the interest has further focused on the preliminary diagnosis of various types of benign or malignant tumors. In cases of inoperable tumors, this technique is useful for formulating the final diagnosis. FNA biopsy proved its effectiveness as a highly accurate, cost-effective, and safe technique, with potential high diagnostic yield. Immunohistochemistry, used as an additional tool to classical histopathological examination, remains a very practical and reliable technique that promises good results especially in determining the site of origin within metastatic disease.

Histopathological and Immunohistochemical Mechanisms of Bone Marrow-Derived Mesenchymal Stem Cells in Reversion of Gastric Precancerous Lesions.

BACKGROUND: Gastric cancer (GC) stands as one of the most prevalent cancer types worldwide, holding the position of the second leading cause of cancer-related deaths. Gastric lesions represent pathological alterations to the gastric mucosa, with an elevated propensity to advance to gastric cancer. Limited research has explored the potential of stem cells in the treatment of gastric lesions. METHODS: This study aimed to explore the potential of intravenous transplantation of labeled bone marrow-derived mesenchymal stem cells (BMMSCs) to inhibit the progression of precancerous gastric lesions. RESULTS: In the gastric lesion disease model group, the rat tissue exhibited noteworthy mucosal atrophy, intestinal metaplasia, dysplasia, and inflammatory cell infiltration. Following the infusion of BMMSCs, a notable decrease in gastric lesions was found, with atrophic gastritis being the sole remaining lesion, which was confirmed by morphological and histological examinations. BMMSCs that were colonized at gastric lesions could differentiate into epithelial and stromal cells, as determined by the expression of pan-keratin or vimentin. The expression of vascular endothelial growth factor was significantly elevated following BMMSC transplantation. BMMSCs could also upregulate the production of humoral immune response cytokines, including interleukin (IL)-4 and IL-10, and downregulate the production of IL-17 and interferon-gamma, which could be highly associated with the cellular immune response and inflammation severity of the lesions. CONCLUSIONS: BMMSC transplantation significantly reduced inflammation and reversed gastric lesion progression.

Cervical Cancer Screening via Visual Inspection With Acetic Acid and Lugol Iodine for Triage of HPV-Positive Women.

Importance: Limited evidence supports the performance of human papillomavirus (HPV) DNA testing as a primary screening method, followed by triage with visual inspection with acetic acid, in areas with limited health care resources, as suggested by the 2021 World Health Organization guidelines. Objective: To evaluate the performance of visual inspection with acetic acid and Lugol iodine as a triage method for detecting cervical precancerous lesions among HPV-positive women in 1 visit. Design, Setting, and Participants: This cohort study examined the implementation of a government-led cervical cancer screening program conducted from January 1, 2016, to December 31, 2020, in Ordos City, China. Female residents, aged 35 to 64 years, who understood the screening procedures and voluntarily participated were included in the study. Women were excluded if they reported never having had sexual intercourse, were pregnant, had a hysterectomy, or had ever undergone treatment for cervical lesions. Statistical analysis was conducted from December 2022 to December 2023. Exposures: The program used the careHPV DNA assay as the primary screening method, and immediate triage was performed by visual inspection if HPV screening results were positive, with a 5-year screening interval. A colposcopy was performed for the women who had suspected cancer on visual inspection results or who were HPV positive and had abnormal visual inspection results, all in 1 visit. Main Outcomes and Measures: The rate of compliance with colposcopy and the detection rate of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). Results: The study included 187 863 women (median age, 46 years [IQR, 40-52 years]) who participated in the program and had valid HPV test results. The overall prevalence of HPV positivity was 12.8% (24 070 of 187 863), and the adherence to triage with visual inspection among HPV-positive women was 93.9% (22 592 of 24 070). Among HPV-positive women, the rate of compliance with colposcopy was 65.6% (2714 of 4137), and the CIN2+ detection rate was 2.8% (643 of 22 592). Conclusions and Relevance: The findings of this cohort study suggest that the implementation of HPV testing, visual inspection, and colposcopy within 1 visit may mitigate losses to follow-up, detect precancerous lesions, and hold significant implications for screening in comparable areas with limited health care resources.

Molecular pathological approach to cancer epigenomics and its clinical application.

Careful microscopic observation of histopathological specimens, accumulation of large numbers of high-quality tissue specimens, and analysis of molecular pathology in relation to morphological features are considered to yield realistic data on the nature of multistage carcinogenesis. Since the morphological hallmark of cancer is disruption of the normal histological structure maintained through cell-cell adhesiveness and cellular polarity, attempts have been made to investigate abnormalities of the cadherin-catenin cell adhesion system in human cancer cells. It has been shown that the CDH1 tumor suppressor gene encoding E-cadherin is silenced by DNA methylation, suggesting that a "double hit" involving DNA methylation and loss of heterozygosity leads to carcinogenesis. Therefore, in the 1990s, we focused on epigenomic mechanisms, which until then had not received much attention. In chronic hepatitis and liver cirrhosis associated with hepatitis virus infection, DNA methylation abnormalities were found to occur frequently, being one of the earliest indications that such abnormalities are present even in precancerous tissue. Aberrant expression and splicing of DNA methyltransferases, such as DNMT1 and DNMT3B, was found to underlie the mechanism of DNA methylation alterations in various organs. The CpG island methylator phenotype in renal cell carcinoma was identified for the first time, and its therapeutic targets were identified by multilayer omics analysis. Furthermore, the DNA methylation profile of nonalcoholic steatohepatitis (NASH)-related hepatocellular carcinoma was clarified in groundbreaking studies. Since then, we have developed diagnostic markers for carcinogenesis risk in NASH patients and noninvasive diagnostic markers for upper urinary tract cancer, as well as developing a new high-performance liquid chromatography-based diagnostic system for DNA methylation diagnosis. Research on the cancer epigenome has revealed that DNA methylation alterations occur from the precancerous stage as a result of exposure to carcinogenic factors such as inflammation, smoking, and viral infections, and continuously contribute to multistage carcinogenesis through aberrant expression of cancer-related genes and genomic instability. DNA methylation alterations at the precancerous stages are inherited by or strengthened in cancers themselves and determine the clinicopathological aggressiveness of cancers as well as patient outcome. DNA methylation alterations have applications as biomarkers, and are expected to contribute to diagnosis, as well as preventive and preemptive medicine.

Secondary solid malignancies and precancerous lesions after allogeneic hematopoietic stem cell transplantation using non-total body irradiation-based conditioning in acute myeloid leukemia.

INTRODUCTION: Long-term survivors have an increased risk of developing secondary solid malignancies (SSMs) after allogeneic-hematopoietic stem cell transplantation (allo-HSCT) with graft-versus-host disease (GVHD) potentially modulating these risks. METHODS: This retrospective study analyzed the cumulative incidences of SSMs after chemotherapy-based conditioning for allo-HSCT patients with acute myeloid leukemia (n = 266) transplanted at the University Hospital Regensburg between 1999 and 2016. RESULTS: The median follow-up was 11.4 years (Interquartile range, 9.0-14.9). The 100-day cumulative incidence of grade II-IV acute GVHD (aGVHD) was 44.4% [95% CI (38.3, 50.2)], while the 5-year cumulative incidence of chronic GVHD (cGVHD, requiring systemic immunosuppression) was 36.9% [95% CI (31.1, 42.6)]. The cumulative incidences of secondary squamous cell carcinomas (SCCs) at 10 and 15 years were 4.2% [95% CI (2.2, 7.2)] and 8.1% [95% CI (4.6, 12.8)], while the cumulative incidences of non-SCCs at 10 and 15 years were 5.4% [95% CI (3.1, 8.7)] and 6.9% [95% CI (4.0, 10.8)]. Antithymocyte globulin (ATG) was associated with reduced incidences of SCCs but not of non-SCCs. Patients with grade II-IV aGVHD had increased rates of SCCs after adjusting with patient age and ATG, while patients with cGVHD showed only a trend for increased rates of SCCs. CONCLUSION: The data indicate that aGVHD and cGVHD affect the rates of secondary SCCs. While the use of ATG is associated with lower incidences of SCCs via reduction of GVHD, there was no association of ATG with non-SCCs.

Machine learning methods in predicting the risk of malignant transformation of oral potentially malignant disorders: A systematic review.

BACKGROUND: Oral Potentially Malignant Disorders (OPMDs) refer to a heterogenous group of clinical presentations with heightened rate of malignant transformation. Identification of risk levels in OPMDs is crucial to determine the need for active intervention in high-risk patients and routine follow-up in low-risk ones. Machine learning models has shown tremendous potential in several areas of dentistry that strongly suggest its application to estimate rate of malignant transformation of precancerous lesions. METHODS: A comprehensive literature search was performed on Pubmed/MEDLINE, Web of Science, Scopus, Embase, Cochrane Library database to identify articles including machine learning models and algorithms to predict malignant transformation in OPMDs. Relevant bibliographic data, study characteristics, and outcomes were extracted for eligible studies. Quality of the included studies was assessed through the IJMEDI checklist. RESULTS: Fifteen articles were found suitable for the review as per the PECOS criteria. Amongst all studies, highest sensitivity (100%) was recorded for U-net architecture, Peaks Random forest model, and Partial least squares discriminant analysis (PLSDA). Highest specificity (100%) was noted for PLSDA. Range of overall accuracy in risk prediction was between 95.4% and 74%. CONCLUSION: Machine learning proved to be a viable tool in risk prediction, demonstrating heightened sensitivity, automation, and improved accuracy for predicting transformation of OPMDs. It presents an effective approach for incorporating multiple variables to monitor the progression of OPMDs and predict their malignant potential. However, its sensitivity to dataset characteristics necessitates the optimization of input parameters to maximize the efficiency of the classifiers.

Frequency of Clinically Significant Findings in the Surgical Pathology Specimen Following Laparoscopic Sleeve Gastrectomy and Concordance with Preoperative Endoscopy: Insights from a Large Single-Center Experience.

INTRODUCTION: Endoscopy prior to bariatric surgery is not always performed, and in sleeve gastrectomy (SG), the surgical specimen is not always sent for pathological examination. There is limited data on the frequency of clinically significant findings in SG specimens or correlation with preoperative endoscopy. METHODS: We reviewed 426 consecutive SG patients to determine the concordance of preoperative endoscopy findings in patients with clinically significant postoperative pathology. RESULTS: Preoperative endoscopy was performed on 397 patients (93.2%). Three hundred seventy-three patients had preoperative endoscopy and surgical pathology results available. Then, 20/373 (5.4%) patients had potentially significant postoperative pathology, including intestinal metaplasia, autoimmune metaplastic atrophic gastritis (AMAG), gastrointestinal stromal tumors, and/or gastric cancer. The overall incidence of AMAG in the entire cohort was 2.3%. Preoperative gastric biopsies (to include gastric body) identified AMAG in nearly 1/2 of patients. Patients with clinically significant postoperative pathology results had a median [interquartile range] of 3 [3-5] tissue blocks examined as compared to 3 [1-3] for the remainder of the cohort (p < 0.001). CONCLUSION: This is one of the largest studies describing clinically significant postoperative pathology after SG. AMAG, in particular, is of particular importance as it is associated with a 3-fivefold increase in risk for gastric cancer. The incidence of significant postoperative pathology in this population is small but potentially clinically significant and requires validation in larger studies. We recommend wider sampling in preoperative endoscopy (body and antrum), especially in patients being planned for gastric bypass, consideration for routine pathological examination of SG surgical specimens, with careful gross examination and targeted sampling.

EGFR and HER-2 oncogenes expression in an experimental model of two-stage chemically induced carcinogenesis in mouse skin.

The aim of the study was to investigate the expression of EGFR and HER-2 oncogenes using an experimental two stage chemically induced carcinogenesis protocol on the dorsal skin in FVB/N mice. Forty female FVB/N mice 4 weeks old, were grouped into one control (n = 8) and two experimental groups (Group A: n = 16, Group B: n = 16) following a randomization process. Two-stage carcinogenesis protocol, was implicated, including an initial treatment with 97.4 nmol DMBA on their shaved dorsal skin and subsequent treatments of 32.4 nmol TPA applications after 13 weeks for Group A and after 20 weeks for Group B. The control group C, received no treatment. Skin was examined weekly for tumor development. Post-experiment, animals were euthanized for tissue analysis. The histological status of the skin lesions in the experimental groups corresponded well with tumour advancement (from dysplasia to poorly-differentiated carcinoma). Tumour sections were evaluated histologically and immunohistochemically. EGFR expression was found significantly higher in precancerous and malignant tumours (p = 042 and p = 008 respectively), while tended to be higher in benign tumours (p = 079), compared to normal histology. Moreover, mean percentage of EGFR positive expression in malignant tumours was significantly higher than in benign tumours (p < 001). HER-2 expression was found significantly higher in precancerous and malignant tumours (p = 042 and p = 015 respectively), while tended to be higher in benign tumours (p = 085), compared to normal histology. Furthermore, mean percentage of HER-2 positive expression in malignant tumours was significantly higher than in benign tumours (p = 005). The study demonstrated that in FVB/N mice subjected to a two-stage chemically induced carcinogenesis protocol, there was a significant increase in the expression of EGFR and HER-2 oncogenes in precancerous and malignant skin lesions compared to normal tissue. This suggests a potentially early role of these oncogenes in the progression of skin tumours in this model.

Medical management determinants of the maxillofacial precancerous and benign diseases malignancy.

OBJECTIVE: Aim: To identify the medical management determinants of the maxillofacial precancerous and benign diseases malignancy. PATIENTS AND METHODS: Materials and Methods: 150 people with maxillofacial cancer and 100 people with precancerous and benign diseases of the same localization were interviewed. RESULTS: Results: There were revealed: a low percentage of detection during check-up (10.2-15.8%), more than a third of cases (35.8-37.4%) are diagnosed by chance; not all patients undergo histological verification of the diagnosis (25.7% in cancerous and 43.2% in precancerous and benign diseases); not all are under follow up observation (24.7-27.7%). The risk of precancerous and benign diseases malignancy is the highest at 40-59 years of age (OR=4.4; 95% CI: 1.9-10.5), andalso increases with the duration of the disease for more than 5 years (2.2; 1.2-4.10 ), in patients who didn't undergo histological verification (2.2; 1.3-3.8), don't follow doctors' recommendation on visits and treatment (2.4; 1.4-4.1), don't trust doctors and are dissatisfied with medical care (2.1; 1.3-3.6). The risk groups of the maxillofacial oncological, precancerous and benign diseases are men, who are 1.5 times more likely to suffer from them than women and are characterized by lower medical care activity. The risk factors of the maxillofacial precancerous and benign diseases malignancy are low financial (4.6; 1.7-12.4) and territorial (3.3; 1.1-10.3) accessibility of medical care, including dental care (2.8; 1.6-4.8). CONCLUSION: Conclusions: It is necessary to improve the prevention and medical care in order to advance the early detection of maxillofacial cancer, taking into account the established medical management determinants of malignancy.

A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening.

BACKGROUND: Colorectal cancer is the third most diagnosed cancer in adults in the United States. Early detection could prevent more than 90% of colorectal cancer-related deaths, yet more than one third of the screening-eligible population is not up to date with screening despite multiple available tests. A blood-based test has the potential to improve screening adherence, detect colorectal cancer earlier, and reduce colorectal cancer-related mortality. METHODS: We assessed the performance characteristics of a cell-free DNA (cfDNA) blood-based test in a population eligible for colorectal cancer screening. The coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) relative to screening colonoscopy. The secondary outcome was sensitivity to detect advanced precancerous lesions. RESULTS: The clinical validation cohort included 10,258 persons, 7861 of whom met eligibility criteria and were evaluable. A total of 83.1% of the participants with colorectal cancer detected by colonoscopy had a positive cfDNA test and 16.9% had a negative test, which indicates a sensitivity of the cfDNA test for detection of colorectal cancer of 83.1% (95% confidence interval [CI], 72.2 to 90.3). Sensitivity for stage I, II, or III colorectal cancer was 87.5% (95% CI, 75.3 to 94.1), and sensitivity for advanced precancerous lesions was 13.2% (95% CI, 11.3 to 15.3). A total of 89.6% of the participants without any advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions) identified on colonoscopy had a negative cfDNA blood-based test, whereas 10.4% had a positive cfDNA blood-based test, which indicates a specificity for any advanced neoplasia of 89.6% (95% CI, 88.8 to 90.3). Specificity for negative colonoscopy (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0 to 90.7). CONCLUSIONS: In an average-risk screening population, this cfDNA blood-based test had 83% sensitivity for colorectal cancer, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions. (Funded by Guardant Health; ECLIPSE ClinicalTrials.gov number, NCT04136002.).