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Clinical and Translational... Oct 2023Colorectal cancer screening plays a vital role in early detection and removal of precancerous adenomas, contributing to decreased mortality rates. Most polyps found... (Review)
Review
Colorectal cancer screening plays a vital role in early detection and removal of precancerous adenomas, contributing to decreased mortality rates. Most polyps found during colonoscopies are small and unlikely to harbor advanced neoplasia or invasive cancer, leading to the development of "leave-in-situ" and "resect-and-discard" approaches. These strategies could lead to significant cost savings and efficiencies, but their implementation has been hampered by concerns around financial incentives, medical-legal risks, and local rules for tissue handling. This article reviews the potential of artificial intelligence to enhance the accuracy of polyp diagnosis through computer-aided diagnosis (CADx). While the adoption of CADx in optical biopsy has shown mixed results, it has the potential to significantly improve the management of colorectal polyps. Several studies reviewed in this article highlight the varied results of CADx in optical biopsy for colorectal polyps. Although artificial intelligence does not consistently outperform expert endoscopists, it has the potential to serve as a beneficial secondary reader, aiding in accurate optical diagnosis and increasing the confidence of the endoscopist. These studies indicate that although CADx holds great potential, it is yet to fully meet the performance thresholds necessary for clinical implementation.
Topics: Humans; Colonic Polyps; Artificial Intelligence; Colonoscopy; Adenoma; Narrow Band Imaging
PubMed: 37747097
DOI: 10.14309/ctg.0000000000000640 -
Medicina (Kaunas, Lithuania) Oct 2023Proper bowel preparation is of paramount importance for enhancing adenoma detection rates and reducing postcolonoscopic colorectal cancer risk. Despite recommendations... (Review)
Review
BACKGROUND AND OBJECTIVES
Proper bowel preparation is of paramount importance for enhancing adenoma detection rates and reducing postcolonoscopic colorectal cancer risk. Despite recommendations from gastroenterology societies regarding the optimal rates of successful bowel preparation, these guidelines are frequently unmet. Various approaches have been employed to enhance the rates of successful bowel preparation, yet the quality of cleansing remains suboptimal. Intensive bowel preparation techniques, supplementary administration of bowel solutions, and educational interventions aimed at improving patient adherence to instructions have been commonly utilized, particularly among patients at a high risk of inadequate bowel preparation. Expedited strategies conducted on the same day as the procedure have also been endorsed by scientific organizations. More recently, the utilization of artificial intelligence (AI) has emerged for the preprocedural detection of inadequate bowel preparation, holding the potential to guide the preparation process immediately preceding colonoscopy. This manuscript comprehensively reviews the current strategies employed to optimize bowel cleansing, with a specific focus on patients with elevated risks for inadequate bowel preparation. Additionally, the prospective role of AI in this context is thoroughly examined.
CONCLUSIONS
While a majority of outpatients may achieve cleanliness with standard cleansing protocols, dealing with hard-to-prepare patients remains a challenge. Rescue strategies based on AI are promising, but such evidence remains limited. To ensure proper bowel cleansing, a combination of strategies should be performed.
Topics: Humans; Cathartics; Artificial Intelligence; Colon; Colonoscopy; Adenoma
PubMed: 37893552
DOI: 10.3390/medicina59101834 -
Cancer Letters Mar 2024The highly heterogenous nature of colorectal cancer can significantly hinder its early and accurate diagnosis, eventually contributing to high mortality rates. The... (Review)
Review
The highly heterogenous nature of colorectal cancer can significantly hinder its early and accurate diagnosis, eventually contributing to high mortality rates. The adenoma-carcinoma sequence and serrated polyp-carcinoma sequence are the two most common sequences in sporadic colorectal cancer. Genetic alterations in adenomatous polyposis coli (APC), v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and tumour protein 53 (TP53) genes are critical in adenoma-carcinoma sequence, whereas v-Raf murine sarcoma viral oncogene homolog B (BRAF) and MutL Homolog1 (MLH1) are driving oncogenes in the serrated polyp-carcinoma sequence. Sporadic mutations in these genes contribute differently to colorectal cancer pathogenesis by introducing distinct alterations in several signalling pathways that rely on the endosome-lysosome system. Unsurprisingly, the endosome-lysosome system plays a pivotal role in the hallmarks of cancer and contributes to specialised colon function. Thus, the endosome-lysosome system might be distinctively influenced by different mutations and these alterations may contribute to the heterogenous nature of sporadic colorectal cancer. This review highlights potential connections between major sporadic colorectal cancer mutations and the diverse pathogenic mechanisms driven by the endosome-lysosome system in colorectal carcinogenesis.
Topics: Animals; Mice; Humans; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Colorectal Neoplasms; Mutation; Adenoma; Carcinoma
PubMed: 38290660
DOI: 10.1016/j.canlet.2024.216639 -
Clinical Epigenetics Oct 2023Early detection has proven to be the most effective strategy to reduce the incidence and mortality of colorectal cancer (CRC). Nevertheless, most current screening...
BACKGROUND
Early detection has proven to be the most effective strategy to reduce the incidence and mortality of colorectal cancer (CRC). Nevertheless, most current screening programs suffer from low participation rates. A blood test may improve both the adherence to screening and the selection to colonoscopy. In this study, we conducted a serum-based discovery and validation of cfDNA methylation biomarkers for CRC screening in a multicenter cohort of 433 serum samples including healthy controls, benign pathologies, advanced adenomas (AA), and CRC.
RESULTS
First, we performed an epigenome-wide methylation analysis with the MethylationEPIC array using a sample pooling approach, followed by a robust prioritization of candidate biomarkers for the detection of advanced neoplasia (AN: AA and CRC). Then, candidate biomarkers were validated by pyrosequencing in independent individual cfDNA samples. We report GALNT9, UPF3A, WARS, and LDB2 as new noninvasive biomarkers for the early detection of AN. The combination of GALNT9/UPF3A by logistic regression discriminated AN with 78.8% sensitivity and 100% specificity, outperforming the commonly used fecal immunochemical test and the methylated SEPT9 blood test.
CONCLUSIONS
Overall, this study highlights the utility of cfDNA methylation for CRC screening. Our results suggest that the combination methylated GALNT9/UPF3A has the potential to serve as a highly specific and sensitive blood-based test for screening and early detection of CRC.
Topics: Humans; DNA Methylation; Early Detection of Cancer; Sensitivity and Specificity; Biomarkers, Tumor; Cell-Free Nucleic Acids; Colorectal Neoplasms; Septins; Adenoma; RNA-Binding Proteins; Transcription Factors; LIM Domain Proteins
PubMed: 37794510
DOI: 10.1186/s13148-023-01570-1 -
Frontiers in Immunology 2024Colorectal cancer (CRC) is the third most prevalent cancer worldwide and is associated with high morbidity and mortality rates. Colorectal carcinogenesis occurs via the...
OBJECTIVE
Colorectal cancer (CRC) is the third most prevalent cancer worldwide and is associated with high morbidity and mortality rates. Colorectal carcinogenesis occurs via the conventional adenoma-to-carcinoma and serrated pathways. Conventional T helper (Th) and innate lymphoid cells (ILCs) play vital roles in maintaining intestinal homeostasis. However, the contribution of these two major lymphoid cell populations and their associated cytokines to CRC development is unclear. Therefore, we aimed to analyze peripheral lymphocyte profiles during colorectal carcinogenesis.
METHODS
We collected 86 blood samples concurrently, and pathologists confirmed the presence of various pathological conditions (i.e., HPs, adenoma, and carcinoma) using hematoxylin and eosin staining. Ten healthy donors were recruited as healthy controls (HCs) from the physical examination center. We performed flow cytometry on peripheral blood mononuclear cells collected from patients with various pathological conditions and the HCs, and cytokines (interleukin-2, interleukin-4, interleukin-5, interleukin-13, interleukin-17A, interleukin-17F, interleukin-22, interferon-γ, and tumor necrosis factor-α) were quantified. We also analyzed the published single-cell RNA sequence data derived from tissue samples from different stages of colorectal carcinogenesis.
RESULTS
The cytokine response in peripheral CD4 T cells was upregulated during the carcinoma process. The frequency of peripheral regulatory T cells (Tregs) increased in the adenoma and carcinoma stages. While the T follicular helper (Tfh) cell proportion was downregulated in the adenoma and carcinoma processes. Thus, Th cell subsets, especially Tregs and Tfh cells, were involved in colonic diseases. Moreover, the immunological profile characteristics in the HPs were clarified.
CONCLUSION
We comprehensively analyzed circulating ILCs and adaptive T-cell lymphocyte subtypes in colorectal carcinoma progression. Our results show the immunological profile characteristics and support the involvement of Th subsets, especially Treg and Tfh cell populations, in colonic diseases. These findings significantly enhance our understanding of the immune mechanisms underlying CRC and its precancerous lesions. Further investigation of the Treg and Tfh cells' function in colorectal disease development will provide potential therapeutic targets for monitoring and preventing CRC development.
Topics: Humans; T-Lymphocytes, Regulatory; Leukocytes, Mononuclear; Immunity, Innate; Lymphocytes; T-Lymphocytes, Helper-Inducer; Cytokines; Colorectal Neoplasms; Colonic Diseases; Carcinoma; Carcinogenesis; Adenoma
PubMed: 38343544
DOI: 10.3389/fimmu.2024.1287632 -
Scientific Reports Sep 2023Cytotoxic CD8 + T cell (CTL) exhaustion is driven by chronic antigen stimulation. Reversing CTL exhaustion with immune checkpoint blockade (ICB) has provided...
Cytotoxic CD8 + T cell (CTL) exhaustion is driven by chronic antigen stimulation. Reversing CTL exhaustion with immune checkpoint blockade (ICB) has provided clinical benefits in different types of cancer. We, therefore, investigated whether modulating chronic antigen stimulation and T-cell receptor (TCR) signaling with an IL2-inducible T-cell kinase (ITK) inhibitor, could confer ICB responsiveness to ICB resistant solid tumors. In vivo intermittent treatment of 3 ICB-resistant solid tumor (melanoma, mesothelioma or pancreatic cancer) with ITK inhibitor significantly improved ICB therapy. ITK inhibition directly reinvigorate exhausted CTL in vitro as it enhanced cytokine production, decreased inhibitory receptor expression, and downregulated the transcription factor TOX. Our study demonstrates that intermittent ITK inhibition can be used to directly ameliorate CTL exhaustion and enhance immunotherapies even in solid tumors that are ICB resistant.
Topics: Humans; Immune Checkpoint Inhibitors; Protein-Tyrosine Kinases; Pancreatic Neoplasms; Mesothelioma
PubMed: 37735204
DOI: 10.1038/s41598-023-42871-y -
Endoscopy Dec 2023Cold snare endoscopic mucosal resection (CS-EMR) can reduce the risks associated with electrocautery during colon polyp resection. Data on efficacy are variable. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cold snare endoscopic mucosal resection (CS-EMR) can reduce the risks associated with electrocautery during colon polyp resection. Data on efficacy are variable. This systematic review and meta-analysis aimed to estimate the pooled efficacy and safety rates of CS-EMR.
METHODS
We conducted a comprehensive literature search of multiple databases, from inception to March 2023, for studies addressing outcomes of CS-EMR for colon polyps. The weighted pooled estimates with 95 %CIs were calculated using the random effects model. statistics were used to evaluate heterogeneity.
RESULTS
4137 articles were reviewed, and 16 studies, including 2592 polyps in 1922 patients (51.4 % female), were included. Overall, 54.4 % of polyps were adenomas, 45 % were sessile serrated lesions (SSLs), and 0.6 % were invasive carcinomas. Polyp recurrence after CS-EMR was 6.7 % (95 %CI 2.4 %-17.4 %, = 94 %). The recurrence rate was 12.3 % (95 %CI 3.4 %-35.7 %, = 94 %) for polyps ≥ 20 mm, 17.1 % (95 %CI 4.6 %-46.7 %, = 93 %) for adenomas, and 5.7 % (95 %CI 3.2 %-9.9 %, = 50 %) for SSLs. The pooled intraprocedural bleeding rate was 2.6 % (95 %CI 1.5 %-4.5 %, = 51 %), the delayed bleeding rate was 1.5 % (95 %CI 0.8 %-2.7 %, = 18 %), and no perforations or post-polypectomy syndromes were reported, with estimated rates of 0.6 % (95 %CI 0.3 %-1.3 %, = 0 %) and 0.6 % (95 %CI 0.3 %-1.4 %, = 0 %), respectively.
CONCLUSION
CS-EMR demonstrated an excellent safety profile for colon polyps, with variable recurrence rates based on polyp size and histology. Large prospective studies are needed to validate these findings.
Topics: Humans; Female; Male; Colonic Polyps; Endoscopic Mucosal Resection; Colonoscopy; Colon; Adenoma; Colorectal Neoplasms
PubMed: 37451284
DOI: 10.1055/a-2129-5752 -
Current Problems in Cancer Dec 2023Pleural mesothelioma (PM) is a cancer of the pleural surface, which is aggressive and may be rapidly fatal. PM is a rare cancer worldwide, but is a relatively common... (Review)
Review
Pleural mesothelioma (PM) is a cancer of the pleural surface, which is aggressive and may be rapidly fatal. PM is a rare cancer worldwide, but is a relatively common disease in Turkey. Asbestos exposure is the main risk factor and the most common underlying cause of the disease. There have been significant improvements in diagnoses and treatments of many malignancies; however, there are still therapeutic challenges in PM. In this review, we aimed to increase the awareness of health care professionals, oncologists, and pulmonologists by underlining the unmet needs of patients with PM and by emphasizing the need for a multidisciplinary treatment and management of PM. After reviewing the general information about PM, we further discuss the treatment options for patients with PM using immunotherapy and offer evidence for improvements in the clinical outcomes of these patients because of these newer treatment modalities.
Topics: Humans; Immunotherapy; Mesothelioma; Pleura; Pleural Neoplasms; Turkey
PubMed: 37845104
DOI: 10.1016/j.currproblcancer.2023.101017 -
Cancer Medicine Aug 2023Colorectal cancer (CRC) screening can help to reduce its incidence and mortality. Noninvasive strategies, such as plasma analysis of epigenetic alterations, can...
BACKGROUND
Colorectal cancer (CRC) screening can help to reduce its incidence and mortality. Noninvasive strategies, such as plasma analysis of epigenetic alterations, can constitute important biomarkers of CRC detection.
OBJECTIVE
This study aimed to evaluate the plasma methylation status of SEPT9 and BMP3 promoters as biomarkers for detection of CRC and its precursor lesions in a Brazilian population.
METHODS
Plasma samples from 262 participants of the CRC screening program of Barretos Cancer Hospital who had a positive fecal occult blood test and underwent colonoscopy and cancer patients were analyzed. Participants were grouped according to the worst lesion detected in the colonoscopy. Cell-free circulating DNA (cfDNA) was bisulfite treated followed by the analysis of SEPT9 and BMP3 methylation status using a droplet digital PCR system (ddPCR). The best methylation cutoff value for group discrimination was calculated by receiver operating characteristic (ROC) curve analysis.
RESULTS
Among the 262 participants, 38 were diagnosed with CRC, 46 with advanced adenomas 119 with nonadvanced adenomas, three with sessile serrated lesions, and 13 with hyperplastic polyps. In 43 participants, no lesion was detected in the colonoscopy and were used as controls. The CRC group showed the highest cfDNA concentration (10.4 ng/mL). For the SEPT9 gene, a cutoff of 2.5% (AUC = 0.681) that discriminates between CRC and the control group resulted in CRC sensitivity and specificity of 50% and 90%, respectively. Concerning the BMP3 gene, a cutoff of 2.3% (AUC = 0.576) showed 40% and 90% of sensitivity and specificity for CRC detection, respectively. Combining SEPT9, BMP3 status, and age over 60 years resulted in a better performance for detecting CRC (AUC = 0.845) than the individual gene models, yielding 80% and 81% of sensitivity and specificity, respectively.
CONCLUSION
The present study suggests that a combination of SEPT9 and BMP3 plasma methylation, along with age over 60 years, showed the highest performance in detecting CRC in a Brazilian population. These noninvasive biomarkers can potentially serve as useful tools for CRC screening programs.
Topics: Humans; Middle Aged; Early Detection of Cancer; Brazil; DNA Methylation; Septins; Colorectal Neoplasms; Sensitivity and Specificity; Cell-Free Nucleic Acids; Adenoma; Biomarkers, Tumor; Bone Morphogenetic Protein 3
PubMed: 37338022
DOI: 10.1002/cam4.6224 -
Pathology, Research and Practice Aug 2023Pituitary adenomas are slow-growing tumors originated from the anterior part of pituitary gland. These tumors are associated with dysregulation of a number of long...
Pituitary adenomas are slow-growing tumors originated from the anterior part of pituitary gland. These tumors are associated with dysregulation of a number of long non-coding RNAs (lncRNAs). PVT1, TUG1, MALAT1, NEAT1 and GAS5 are among lncRNAs with important roles in the regulation of cell proliferation, cell apoptosis, cell differentiation and cell cycle transition. In the current study, we assessed expression levels of PVT1, TUG1, MALAT1, NEAT1 and GAS5 in the pituitary adenoma samples compared with adjacent non-cancerous samples to find their relevance with this type of tumors and their potential as diagnostic markers in these tumors. Expression of NEAT1 was significantly higher in total adenoma tissues (Expression ratio (95% CI)= 7.06 (2.31-21.4), P value= 0.02) and in non-functioning pituitary adenoma (NFPA) samples (Expression ratio (95% CI)= 8.5 (2.17-33.12), P value= 0.04) compared with corresponding controls. Although both lncRNAs had appropriate sensitivity values for discrimination of NFPAs from adjacent non-cancerous tissues (0.84 and 0.90 for PVT1 and NEAT1, respectively), the calculated AUC values were not adequate for either lncRNAs (0.63 ± 0.04 and 0.58 ± 0.04 for PVT1 and NEAT1, respectively). Therefore, NEAT1 and PVT1 lncRNAs are dysregulated in NFPA. The current study suggests the role of NEAT1 and PVT1 in the pathogenesis of NFPA.
Topics: Humans; Adenoma; Cell Proliferation; Gene Expression Regulation, Neoplastic; Pituitary Neoplasms; RNA, Long Noncoding
PubMed: 37270938
DOI: 10.1016/j.prp.2023.154573