Search Results (146)

Accounting for 15–30% of colorectal cancer cases, the serrated pathway remains poorly characterized compared to the adenoma–carcinoma sequence. It involves sessile serrated lesions as precursors and is characterized by BRAF mutations (BRAF^V600E), CpG island hypermethylation, and microsatellite instability (MSI). Using label-free proteomics, we compared normal tissue margins from patients with diverticular disease, sessile serrated lesions, low-grade adenomas, and high-grade adenomas. We identified S100A14 as significantly overexpressed in sessile serrated lesions compared to low-grade adenomas, high-grade adenomas, and normal tissues. This overexpression was confirmed by immunohistochemical scoring in an independent cohort. Gene expression analyses of public datasets showed higher S100A14 expression in BRAF^V600E-mutated and MSI-H colorectal cancers compared to microsatellite stable BRAF^wt tumors. This finding was confirmed by immunohistochemical scoring in an independent colorectal cancer cohort. Furthermore, single-cell RNA sequencing analysis from the Human Colon Cancer Atlas revealed that S100A14 expression in tumor cells positively correlated with the abundance of tumoral CD8⁺ cytotoxic T cells, particularly the CD8⁺ CXCL13⁺ subset, known for its association with a favorable response to immunotherapy. Collectively, our results demonstrate for the first time that S100A14 is a potential biomarker of serrated neoplasia and further suggests its potential role in predicting immunotherapy responses in colorectal cancer. Full article

Background/Objectives: White light imaging (WLI) of colonoscopy has a 26% adenoma miss rate. We aimed to evaluate the effectiveness of an additional 30 s (Add-30s) observation of the right-sided colon using a novel system (EVIS X1; Olympus Co.) with texture and color enhancement imaging (TXI). Methods: We reviewed 515 patients who underwent colonoscopy with Add-30s TXI between February 2021 and December 2023 at three affiliated hospitals. After initial right-sided colon observation with WLI, the colonoscope was reinserted into the cecum, and the right-sided colon was re-observed with Add-30s TXI. Adenoma and sessile serrated lesion (SSL) detection rate (ASDR) and adenoma detection rate (ADR) were examined. Multivariate analysis identified factors influencing lesion detection using the Add-30s TXI. The difference in WLI and TXI between the novel and previous scopes was performed using propensity score matching (PSM). The efficacy of WLI with the novel system was compared to that of the previous system. Results: Among the 515 cases, Add-30s TXI observation increased right-sided ADR and ASDR by 7.4% and 9.5%, respectively. The multivariate analysis showed novel scope as an independent factor for adenoma and SSL detection (odds ratio: 2.41, p < 0.01). Right-sided ADR and ASDR for Add-30s TXI were significantly higher in the novel scope than the previous scope (ADR, 25.2% vs. 15.3%; p = 0.04; ASDR, 32.4% vs. 18.9%; p = 0.02). ASDR for WLI observation was significantly higher in the novel system than the previous system (34.8% vs. 25.9%; p < 0.01). Conclusions: Add-30s TXI significantly improved the detection of missed adenomas and SSLs in the right-sided colon. Full article

Current systemic therapies for advanced colorectal cancer (CRC) have limited efficacy, so more effective strategies for the treatment and prevention of CRC are needed. The majority of colorectal cancers are initiated by mutations in Wnt signalling pathway genes, including mutations in the APC gene, which result in a truncated APC protein and lead to excess signalling from β-catenin and the formation of pre-cancerous adenomas. The aim of this study was to determine if targeting the Wnt pathway in combination with pro-apoptotic mimetics altered the proliferative capacity or viability of human colorectal adenoma cells. Patient-derived colorectal adenoma organoid cultures were established from colon adenoma tissue collected by colonoscopy and recapitulated the histopathology of primary colorectal adenoma tissue. The growth of colorectal adenoma organoids is inhibited by the Wnt-signalling antagonist pyrvinium pamoate (PP) and a pro-apoptotic inhibitor of BCL-XL but not BCL-2 (venetoclax) or MCL-1 inhibitors. At low concentrations, the PP and the BCL-XL inhibitor combination demonstrated potent synergy and induced apoptosis in APC-defective patient-derived adenoma organoids, even in the presence of oncogenic KRAS or BRAF mutations, providing a new strategy for colon cancer prevention. Full article

Organoids are three-dimensional (3D) structures that mimic the architecture and functionality of human organs, providing a novel approach to study diseases such as colorectal cancer (CRC). This review aims to explore the impact of organoids on understanding CRC and their potential use in exploring therapeutic outcomes. Colorectal cancer, characterized by the transformation of colonic epithelial cells into adenomas and carcinomas, remains one of the top causes of cancer-related morbidity and mortality worldwide. Traditional two-dimensional (2D) cell cultures fail to replicate the tumor microenvironment in an effective manner, which highlights the need for advanced 3D models. Organoids preserve the genetic and phenotypic properties of the original tumors, allowing for improved disease modeling, drug screening, and personalized medicine applications. When using patient-derived organoids (PDOs), researchers can gain insights into CRC initiation, progression, and treatment outcome. Ultimately, organoids represent an encouraging platform for improving therapeutic strategies for CRC, potentially leading to better patient outcomes through tailored treatment approaches. Full article

Background: Colonoscopy is an important and essential diagnostic and screening tool for colorectal cancer and other pathologies in the colon. High-quality bowel preparation (BP) is a key quality measure of colonoscopy and is critical for maximizing its effectiveness, including enhancing adenoma detection rates. However, inadequate bowel preparation (IBP) remains a frequent challenge and is influenced by multiple factors. This review aims to summarize and evaluate educational and technological interventions implemented before colonoscopy to improve BP quality. Methods: The methodology comprised a structured narrative review of studies published in English, including randomized controlled trials, prospective studies, observational cohorts, and meta-analyses. Interventions were categorized by their delivery mode and impact on BP adequacy. Interventions included written materials, internet-based education modules, short message service (SMS) reminders, visual aids, instructional videos, verbal communication, telephone support, smartphone applications, and virtual reality (VR) platforms. Results: Most studies reported significant improvements in BP quality with enhanced patient education, particularly with the use of instructional videos and smartphone applications. Verbal communication and telephone support also demonstrated positive outcomes but were limited by resource availability. VR represents a promising emerging technology, though its implementation remains costly and complex. Conclusions: Enhanced educational interventions are proven methods to optimize BP quality. The selection of an appropriate modality should consider patient characteristics, technological accessibility, and institutional resources. Personalized strategies targeting high-risk populations can further reduce IBP rates and improve overall colonoscopy outcomes. Full article

The clinicopathologic and molecular features of serrated lesions with dysplasia in inflammatory bowel disease (IBD) remain poorly understood. We examined a total of 2396 patients treated for IBD at the University of Szeged between 2011 and 2023. Among them, 177 (7%) patients were diagnosed with colorectal neoplasia, of which only 11 (6%) had serrated dysplasia (n = 13). Of the 13 lesions, 5 (38%) showed features of sessile serrated lesion (SSL)-like dysplasia; 1 (8%) exhibited characteristics of traditional serrated adenoma (TSA)-like dysplasia; 6 (46%) were classified as serrated dysplasia, not otherwise specified (NOS); and 1 (8%) displayed mixed features of SSL-like and TSA-like dysplasias. At the time of the serrated dysplasia diagnosis, the mean age of the patients was 56 years. Ten (91%) patients had ulcerative colitis, and one (9%) had Crohn’s disease. Pancolitis was observed in seven (64%) patients. The mean duration of IBD at the time of the serrated dysplasia diagnosis was 26 years. Most lesions (n = 9; 69%) were found in the left colon, including SSL-like dysplasia (3/5; 60%) and serrated dysplasia NOS (5/6, 83%). Eleven (85%) lesions had a polypoid endoscopic appearance. The mean size of the serrated dysplasia was 0.8 cm. Most lesions (n = 8; 62%) showed low-grade dysplasia. Serrated dysplasia was often associated with conventional (n = 3; 27%) or nonconventional dysplasia (n = 3; 27%). During the follow-up, 5 (45%) of the 11 patients developed colorectal cancer, including 3 patients with serrated dysplasia NOS, 1 with SSL-like dysplasia, and 1 with TSA-like dysplasia. Whole-exome sequencing revealed that the SSL-like dysplasia harbored mutations in BRAF (p.V600E), MLH1, KRAS, PTEN, POLE, KMT2C, and/or EXT1, whereas the serrated dysplasia NOS showed mutations in TP53, POLG, BRAF (p.G469A), KMT2C, and/or EXT1. One patient with both SSL-like dysplasia and mixed SSL-like/TSA-like dysplasia carried a pathogenic MUTYH (p.R217H) mutation, along with mutations in MADD. Serrated dysplasia was rare in IBD, with a prevalence rate of 6%. The SSL-like dysplasia exhibited distinct clinicopathologic and molecular characteristics compared with its sporadic counterpart. Similarly, serrated dysplasia NOS displayed unique molecular features compared with SSL-like dysplasia and could carry a higher risk of malignancy. Full article

Colonoscopy is an essential diagnostic and therapeutic tool in gastroenterology, significantly impacting colorectal cancer (CRC) detection and management. Effective bowel preparation is critical for optimal visualization, directly influencing colonoscopy accuracy and patient outcomes. However, diabetic patients frequently encounter challenges achieving adequate bowel preparation, primarily due to gastroparesis, autonomic neuropathy, altered colonic motility, fluid–electrolyte imbalances, and complexities related to antihyperglycemic medication adjustments. This review aims to evaluate the current literature on bowel preparation efficacy in diabetic patients undergoing colonoscopy, assess existing guidelines from leading gastroenterological societies, and highlight the necessity for detailed, diabetes-specific recommendations. We conducted a comprehensive PubMed search identifying 20 pertinent studies, including randomized controlled trials, meta-analyses, multicenter studies, cohort studies, and reviews. The findings consistently indicate diabetes as an independent predictor of inadequate bowel preparation. Furthermore, an evaluation of guidelines from the European Society of Gastrointestinal Endoscopy (ESGE), the US Multi-Society Task Force, and the Canadian Association of Gastroenterology revealed either absent or insufficiently detailed diabetes-specific recommendations. Given the rising global prevalence of diabetes and CRC, inadequate bowel preparation significantly impacts the quality of colonoscopy, adenoma detection rates, patient safety, and healthcare costs. This review underscores the urgent need for additional research focusing on tailored bowel preparation strategies for diabetic patients. Ultimately, the implementation of standardized, evidence-based protocols designed explicitly for this high-risk group is essential to enhance diagnostic efficacy, improve patient outcomes, and reduce CRC-related morbidity and mortality. Full article

Aim: Endo-Wing™ is a soft silicone device with six wing-like projections attached at the end of the colonoscope that provides superior visualization by flattening the colonic fold and helps to maintain a central view of the colonoscope during withdrawal. This study aims to compare the adenoma detection rate (ADR) between standard colonoscopy and Endo-Wing™-assisted colonoscopy. Methods: This is a single-center, single-blind, parallel-group, randomized, actively controlled, exploratory clinical trial conducted between July 2019 and April 2020. Participants aged 45 and above who were symptomatic of colorectal cancer (CRC) or with a history of adenoma and under active surveillance were included. Exclusion criteria included colonic strictures, tumors, active colitis, a previous history of polyposis syndrome, colostomy/ileostomy, or a BPPS score of 0. Participants were subsequently randomized to receive standard colonoscopy (n = 96) or Endo-Wing™-assisted colonoscopy (n = 96) at a 1:1 ratio using a central block randomization method with varying block sizes. The primary endpoint was the ADR, and the differences between the two groups were evaluated using univariable statistical methods. Results: The ADR, the number of adenomas, and the size of adenomas in the Endo-Wing™-assisted colonoscopy group were significantly higher compared to standard colonoscopy (p = 0.005, 0.035, and 0.035, respectively). Cecal intubation rates were similar in both groups (p > 0.999). The proportions of colonoscopy requiring increased sedation and standard sedation were similar in both groups (p = 0.613). No adverse effects of bleeding, perforation, and device dislodgement were reported in both groups. Conclusions: This study concludes that Endo-Wing™-assisted colonoscopy improves the ADR compared to standard colonoscopy. Full article

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. The precursor of CRC is a colorectal polyp, of which adenoma is the most common histological type. The initial step in CRC development is the gradual accumulation of a series of genetic and epigenetic alterations in the normal colonic epithelium. Genetic alterations play a major role in a subset of CRCs, but the pathophysiological contribution of epigenetic aberrations has recently attracted attention. Epigenetic marks occur early in cancer pathogenesis and are therefore important molecular hallmarks of cancer. This makes some epigenetic alterations clinically relevant for early detection not only of CRC but also of precancerous polyps. In this review we focus on three types of non-coding RNAs as epigenetic regulators: miRNA, lncRNA, and lncRNAs, highlighting their biomarker potential. Full article

Endoscopic full-thickness resection (EFTR) has emerged as a transformative technique for managing gastrointestinal (GI) lesions, previously deemed unsuitable for endoscopic removal. Unlike conventional endoscopic resection methods, such as endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), EFTR enables en bloc excision of both intraluminal and subepithelial lesions by resecting all layers of the GI wall, followed by defect closure to prevent complications. The introduction of the full-thickness resection device (FTRD^®) has significantly enhanced the feasibility and safety of EFTR, particularly in the colon and upper GI tract, with increasing adoption worldwide. This review provides a comprehensive analysis of FTRD^®, focusing on its clinical applications, procedural methodology, and comparative efficacy against other endoscopic resection techniques. The indications and contraindications for EFTR are explored, highlighting its utility in treating non-lifting adenomas, subepithelial tumours, and T1 carcinomas without lymph node involvement. This review synthesizes current clinical data and FTRD^® advantages. Despite its strengths, EFTR via FTRD^® incorporates challenges such as limitations in lesion size, procedural complexity, and potential adverse events. Strategies for overcoming these challenges, including hybrid techniques and modifications in procedural approach, are examined. The review also emphasizes the need for further research to optimize surveillance strategies and determine the long-term clinical impact of EFTR in GI lesion management. By integrating recent evidence, this paper provides valuable insights into the evolving role of EFTR in therapeutic endoscopy. Full article

Lung cancer remains the most common cancer worldwide, with a limited prognosis despite personalized treatment regimens. Low-dose computed tomography (CT) scanning as a means of early diagnosis has been disappointing due to the high false positive rate. Other non-invasive means of testing need to be developed that offer both timely diagnosis and predict prognosis. Methods: In the course of stool testing in large-scale testing of 2922 patients at increased risk of CRC, we were able to ascertain 112 patients documented to have prospectively been diagnosed with lung cancer. Stool and colonic effluents were tested for p87 with anti-adenoma antibody (Adnab-9) reactivity by ELISA and Western blot. Survival data were obtained where available. Results: Of 112 cancers, approximately 27.6% were squamous (SSC), 17.9% were adenocarcinoma, 8% were small, 6.25% were large cell, 3.57% were designated non-small cell cancer (NSCLC), 0.89% were indeterminate, 0.89% were lepidic spread, 3.57% had metastasis, and in 31.25%, data were unavailable. In total, 49.1% of the lung cancer patients had fecal Adnab-9 testing. Overall, 60% had positive testing compared to 38%, which was significant (OR2.19 [1.06–4.53]; p = 0.045). Cancers with higher lethality were less likely to test positive (approximately 8.5% each for both small and large cell lung cancers) and higher, with 56% for SCC and 25% for adenocarcinoma (0% NSCLC). In the larger groups, overall survival was worse in those testing positive: 474 testing positives versus 844 days in SCC and 54 testing positive versus 749 days in adenocarcinoma patients. Most importantly, the time from a positive test to the clinical diagnosis ranged from 2.72 years for small cell, 3.13 for adenocarcinoma, 5.07 for NSCLC, 6.07 for SSC, and 6.24 for large cell cancer. In excluded cases where cancer in the lung was believed to be metastatic, 83.3% of cancers were positive. Conclusions: At a projected real-world sensitivity of 0.60 and specificity of 0.60, and the ability to predate diagnosis by up to 4.7 years overall, this test could help direct lung cancer screening. In addition, the Adnab-9 testing selectively detects worse tumor types (87.5%) and those with worse prognoses amongst the more common, favorable phenotypes, thus making early diagnosis possible in those patients who stand to benefit most from this strategy. Metastatic lung cancer, also detected by the test, should be identified by the follow-up imaging studies and, therefore, would not be considered to be a major pitfall. Full article

Introduction: High-quality colonoscopy is influenced by several factors, with the adenoma detection rate (ADR) being one of the most studied indicators. A strong inverse relationship exists between ADR and the risk of developing post-colonoscopy colorectal cancer (PCCRC), prompting the European Society of Gastrointestinal Endoscopy guidelines to recommend a minimum ADR of 25%. In contrast, there is limited evidence supporting the clinical significance of the serrated polyp detection rate (SPDR), and no specific benchmark was established until a very recent update from the American societies. Main paper: This review examines the factors that influence ADR and SPDR, offering tips to improve these metrics. Effective interventions for enhancing ADR include training, colonoscopy feedback, adequate bowel preparation, longer withdrawal time, water-aided colonoscopy, right colon second look, and chromoendoscopy. The use of cap, devices, and specialized scopes also show promise, though these are often at higher costs. Artificial intelligence has generated great optimism, especially following positive results from early randomized controlled trials; however, its effectiveness has been less pronounced in real-world settings. Conclusions: Many of these approaches require further trials and meta-analyses to establish their ultimate efficacy. Moreover, future clinical head-to-head studies will help to identify the most effective interventions for reducing colorectal cancer incidence and the risk of PCCRC. Full article

Background/Objectives: Oligopolyposis is a rare condition characterized by 10 to 100 adenomas in the colon. We aimed to investigate the clinical and endoscopic features of patients with oligopolyposis by comparing patients who carried pathogenic mutations and those who did not. Methods: This retrospective study included patients with a cumulative count of 10–100 adenomas found in the colon, at a single center. Clinical, endoscopic, and genetic data were analyzed. Results: A total of 155 patients were identified as having oligopolyposis. Genetic testing using a multigene panel was performed among 85 (55%) patients, while founder or family mutation testing was performed among 7 (4.5%) patients. No genetic testing was carried out in 63 (40.5%) patients. Pathogenic polyposis-related mutations were identified in 14 (16%) out of 85 patients who underwent genetic testing. Among these, seven (50%) mutations were found in the APC gene and seven (50%) in the MUTYH gene. A significantly higher proportion of mutation carriers were of Arab ethnicity (35.7% vs. 4.2%, p < 0.001). There was no significant difference between carriers and non-carriers with regard to family history of polyps or cancer. Colorectal cancer was found to be the initial presentation in three (21%) carriers and five (7%) non-carriers. Colonic surgeries were reported among 4 (28.6%) carriers and 13 (18.6%) non-carriers. No significant differences in the rates of colorectal cancer or death were observed between carriers and non-carriers. Conclusions: Only a small proportion of patients with oligopolyposis were found to be mutation carriers, with significant ethnic differences in mutation frequency but no notable differences in clinical features, colorectal cancer rates, or mortality. Full article

Patients with long-standing inflammatory bowel disease (IBD) involving the colon are at higher risk of developing colorectal dysplastic or neoplastic lesions. While from sporadic colorectal cancer follows an “adenoma-carcinoma” sequence, IBD colitis-associated carcinogenesis is mainly related to an “inflammation-dysplasia-carcinoma” sequence. Currently, specific endoscopic surveillance strategies involving dye spray and virtual chromoendoscopy have been standardized, aiming for early CRC diagnosis. When detected, colitis-associated dysplasia should be classified according to standard classification, thus allowing for better treatment. Indeed, most IBD-associated dysplastic lesions can be treated with endoscopic resection, even though available procedures are usually more challenging than those in the general population. The higher frequency of severe submucosal fibrosis and the difficulty in the definition of lesions’ margins account for this issue. Current endoscopic resection techniques include polypectomy, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Recent evidence suggests the relevance of en bloc resection, as this may be associated with lower rates of recurrence. Therefore, particularly for larger (>20 mm) lesions, ESD should be preferred, even though it is considered the most difficult technique due to frequent severe submucosal fibrosis. Considering the growing number of new endoscopic resective techniques, including underwater EMR or ESD, which in the general population have been suggested to lower procedure-related risks and may also allow a larger spread of advanced endoscopic resection in IBD. However, additional data are needed to assess the medium- and long-term efficacy of endoscopic resection of visible dysplasia in IBD patients, which are burdened by a high risk of local and, more importantly, metachronous recurrence. Full article

Background: Colorectal cancer (CRC) is characterized by the uncontrolled growth of malignant colonic or rectal crypt epithelium. About 85% of CRCs evolve through a stepwise progression from advanced precancerous adenoma lesions. A better understanding of the evolution from adenoma to carcinoma can provide a window of opportunity not only for early detection and therapeutic intervention but potentially also for cancer prevention strategies. Methods: This study investigates the heterogeneous methylation, copy-number alteration (CNA), and mutation signals of histological adenoma subtypes in the context of progression from normal colon to advanced precancerous lesions (APLs) and early-stage CRC. Results: Differential methylation analysis revealed 2321 significantly altered regions among APLs: 137 hypermethylated regions in serrated vs. tubular, 2093 in serrated vs. tubulovillous, and 91 in tubular vs. tubulovillous adenoma subtypes. The most differentiating pathways for serrated adenomas belonged to cAMP signaling and the regulation of pluripotency of stem cells, while regions separating tubular and tubulovillous subtypes were enriched for WNT signaling. CNA events were mostly present in tubular or tubulovillous adenomas, with the most frequent signals being seen in chromosomes 7, 12, 19, and 20. In contrast, early-stage CRC exhibited signals in chromosomes 7, 8, and 20, indicating different processes between APL and early-stage CRC. Mutations reinforce subtype-level differences, showing specific alterations in each subtype. Conclusions: These findings are especially important for developing early detection or cancer prevention tests trying to capture adenoma signatures. Full article