Colorectal Cancer Research Articles

Utilization of molecular genetic approaches for colorectal cancer screening

The feasibility of population screening for colorectal cancer has been demonstrated in several studies. Most of these studies have considered individual characteristics, diagnostic approaches, epidemiological data, and socioeconomic factors. In this article, we comment on an editorial by Metaxas et al published in the recent issue of the journal. The authors emphasized the need to raise public awareness through health education programs and the possibility of using easily accessible non-invasive screening methods. Here, we focus on non-invasive molecular genetic approaches that can aid in colorectal cancer screening. On the one hand, we highlighted the use of tumor DNA/RNA markers directly for screening and, on the other hand, underline the use of polygenic risk assessment and hereditary predisposition to select individuals for more thorough cancer screening.

Establishment of a surveillance program for anal cancer in Crohn's disease

This letter discusses the incidence of anal cancer among Crohn's disease (CD)-related malignancies. Patients with CD have been demonstrated to be at a higher risk of developing small bowel and colorectal cancers than healthy individuals. Although CD-associated anal cancer is relatively rare, patients with CD accompanied by anal or perianal lesions are at increased risk of anal cancer. Additionally, compared to ulcerative colitis, which is also an inflammatory disease, CD-related anal cancer is often detected at an advanced stage owing to the complexity of CD and is associated with a poor prognosis with frequent local recurrences. Therefore, the detection of early-stage cancer is crucial for improving the prognosis. However, the surveillance methods recommended for CD-related malignancies in the United States and Europe are similar to those for ulcerative colitis. They are not appropriate for detecting CD-related malignancies in the recto-anal region. Therefore, there is an urgent need for surveillance programs aimed at the early detection of malignant anorectal lesions in patients with CD.

Importance of Circulating Leptin and Adiponectin in the Causal Pathways Between Obesity and the Development of Colorectal Cancer in Japanese Men.

The mechanistic associations between obesity and risk of colorectal cancer (CRC) remain unclear. Here, using body mass index (BMI) as an obesity indicator, we decomposed the total effects of obesity on the risk of CRC into: (1) direct effects, which are possibly mediated by unmeasured or currently unknown factors; (2) indirect effects mediated by circulating leptin and adiponectin; and (3) indirect effects that are not mediated by circulating leptin and adiponectin but by hyperinsulinemia and chronic inflammation (assessed via circulating connecting peptide and C-reactive protein, respectively). We adopted a causal mediation framework, using data from a large prospective cohort study of 44,271 Japanese men. BMI was not associated with the risk of CRC due to direct and indirect effects that were not mediated by circulating leptin and adiponectin. By contrast, individuals with BMIs of 25.0-27.4 kg/m2 (risk ratio 1.29; 95% confidence interval, 0.98-1.69) and ≥27.5 kg/m2 (risk ratio 1.28; 95% confidence interval, 0.98-1.68) had a higher risk of CRC due to indirect effects of circulating leptin and adiponectin. Our mediation analyses suggest that the association between BMI and CRC risk may be largely mediated by a pathway involving circulating leptin and adiponectin.

Segmental versus extended colectomy for colorectal cancer in patients with lynch syndrome: A systematic review and meta-analysis.

The decision to perform segmental or extended colectomy in Lynch syndrome (LS) patients with colorectal cancer (CRC) is still controversial. Therefore, this systematic review and meta-analysis aims to provide updated evidence for segmental versus extended colectomy in LS carriers with CRC. PubMed, Embase, and Cochrane Library were systematically searched for studies published until January 2024 comparing segmental and extended colectomies for CRC in patients with LS. Risk ratio (RR) was used to evaluate binary endpoints with 95% confidence intervals (CIs). Heterogeneity was assessed with the Cochran's Q test and I2 statistics. Statistical analysis was performed using the R Software, version 4.2.3. A total of 14 studies comprising 2303 LS carriers with CRC, of whom 1724 (74.9%) patients underwent segmental colectomy and 579 (25.1%) patients underwent extended colectomy. Segmental colectomy significantly increased metachronous CRC (mCRC) (RR 2.87; 95% CI 2.03-4.07; and p<0.01). There were no significant differences between groups for 5-year overall survival (OS) (RR 0.92; 95% CI 0.82-1.03; and p=0.14), 10-year OS (RR 0.99; 95% CI 0.96-1.04; and p=0.80), and mortality (RR 1.63; 95% CI 0.90-2.97; and p=0.11). There were no significant linear associations between the outcome of mCRC and age at the time of primary CRC, sex, primary CRC location, and pathogenic LS variant. In this meta-analysis, segmental colectomy significantly increased mCRC compared with extended colectomy after the first surgery for CRC in patients with LS. However, there were no significant differences between groups for 5- and 10-year OS and mortality.

Epigenetic Suppression of miR-137 Induces RNF4 Expression, Facilitating Wnt Signaling in Colorectal Cancer.

Colorectal cancer (CRC) is a significant health issue worldwide. Recent studies highlight the critical role of miRNAs in CRC development, particularly miR-137, which acts as a key tumor suppressor. Despite its known role, further exploration of miR-137's downstream signaling is needed to understand its biology and therapeutic potential. We examined the methylation status of miR-137 using one TCGA data and three GEO data sets. A clinical validation cohort of 78 samples was analyzed using MSP for miR-137 promoter methylation. Various in vitro molecular/cellular and animal experiments were conducted to elucidate miR-137's role in CRC. Bioinformatic analysis indicated frequent methylation of miR-137 in CRC tissues, correlating with suppressed expression. EZH2-mediated H3K27 trimethylation silences miR-137 in CRC cells by increasing chromatin compaction, reversible by EZH2 siRNA or inhibitor GSK343. miR-137 inhibits CRC cell proliferation, migration, invasion, and xenograft tumor growth, confirming its tumor-suppressive role. Using the miRWalk repository showed that miR-137 regulates the Wnt signaling pathway by reducing typical protein expression in HCT116 and SW480 cells. miR-137 directly targets RNF4, leading to its downregulation at transcriptional and protein levels, with an observed inverse correlation in CRC tissues. miR-137 accelerates c-Myc and β-catenin degradation by inhibiting RNF4, impacting protein stability and Wnt pathway inhibition. miR-137 is epigenetically silenced through DNA methylation and EZH2-mediated H3K27 trimethylation. It regulates the Wnt signaling pathway by targeting RNF4, leading to c-Myc and β-catenin destabilization. Restoring miR-137 or inhibiting RNF4 suppresses CRC cell proliferation, migration, invasion, and tumor growth, highlighting its therapeutic potential in CRC.

Evaluating the Implementation and Impact of BRAF Reflex Mutation Testing in Melanoma, Lung, and Colorectal Cancers.

Reflex molecular testing, the process of profiling specimens at diagnosis, is emerging in oncology, allowing for prompt therapy initiation, and potentially improving outcomes. This study evaluates the impact of reflex BRAF testing on treatment timelines and outcomes in melanoma, lung and colorectal cancers at the McGill University Health Center (MUHC). A retrospective chart review was conducted at the MUHC. The study included patients with melanoma, lung, and colorectal cancers who underwent BRAF testing from 2017 to 2022. Data on demographics, cancer type, stage, test ordering specialist, testing method, and treatment outcomes were extracted. Statistical analyses included descriptive and multivariate regression analyses. 518 BRAF molecular tests were performed, with 173 patients meeting the inclusion criteria [median age 72 (IQR 60-80 years), 46.2% female]. Of these, 75.7% had melanoma, 23.7% colorectal cancer and 0.58% lung cancer. Pathologists ordered 71.1% of BRAF tests, primarily relying on immunohistochemistry. By 2022, all BRAF results were available before oncology consultations. Patients with pre-consultation BRAF results were more likely to receive targeted therapy (59.4% vs 36.4%). The availability of BRAF test results was associated with quicker treatment initiation and better alignment of therapy with mutation status. This study underscores the success of the pathology team at MUHC in implementing reflex BRAF mutation testing, enhancing clinical care by ensuring the timely availability of test results. Delays in testing may adversely affect clinical decision-making and therapy selection, highlighting the need for standardized reflex testing protocols across Canada to optimize patient outcomes in melanoma, lung, and colorectal cancers.

The impact of different treatments on thromboelastography and other conventional parameters in patients with colorectal cancer

ObjectiveTo comprehend the effects of diverse therapeutic interventions on thromboelastography (TEG) and conventional coagulation parameters among individuals diagnosed with colorectal cancer, this study aims to explore the clinical relevance of both thromboelastography and conventional coagulation metrics in evaluating coagulation function and predicting the incidence of thrombotic and hemorrhagic events in patients with colorectal cancer.MethodsA cohort of 122 patients with colorectal cancer retrospectively recruited and divided into 2 groups: those undergoing surgical intervention (operation group) and those not subjected to surgery (non-operation group). According to the different types of treatment they received, the operation group was divided into chemotherapy-only group and a group receiving a combination of targeted therapy and chemotherapy. Blood samples were collected on admission and subjected to coagulation parameter assessment, including conventional coagulation tests and thromboelastography (TEG) assessment. Receiver operating characteristic (ROC) analysis was performed to predict the occurrence of complications in patients with colorectal cancer.ResultsCompared with the operation group, the non-operation group showed significant reductions in reaction time(R-time) and kinetics time (K-time), and significant elevation in angle, maximum amplitude (MA), fibrinogen and platelets. Patients receiving targeted therapy and chemotherapy had lower angle and maximum amplitude and higher R-time and K-time, activated partial thromboplastin time and fibrinogen. The area under the curve for TEG in patients without treatment was 0.802. The area under the curve for TEG and conventional coagulation parameters were 0.654 and 0.660 respectively.ConclusionDiverse treatments distinctly impact on the coagulation indicators of individuals diagnosed with colorectal cancer. The coagulation parameters observed in patients prior to operation suggest a hypercoagulable state. Nevertheless, following postoperative chemotherapy and targeted therapy, this hypercoagulable state demonstrates a notable improvement, occasionally leading to a propensity for hypocoagulation. The findings of this investigation underscore the unique clinical importance of thromboelastography (TEG) alongside traditional coagulation parameters, demonstrating that these diagnostic tools possess complementary value and cannot be substituted interchangeably.

Colorectal cancer patients-derived immunity-organoid platform unveils cancer-specific tissue markers associated with immunotherapy resistance

Colorectal cancer (CRC) is a devastating disease, ranking as the second leading cause of cancer-related deaths worldwide. Immune checkpoint inhibitors (ICIs) have emerged as promising treatments; however, their efficacy is largely restricted to a subgroup of microsatellite instable (MSI) CRCs. In contrast, microsatellite stable (MSS) CRCs, which account for the majority of cases, exhibit variable and generally weaker response to ICIs, with only a subset demonstrating exceptional responsiveness. Identifying novel cancer-specific tissue (CST) markers predictive of immunotherapy response is crucial for refining patient selection and overcoming treatment resistance. In this study, we developed clinically relevant CRC organoids and autologous immune system interaction platforms to model ICI response. We conducted a comprehensive molecular characterization of both responder and non-responder models, identifying CST markers that predict ICI response. Validation of these findings was performed using an independent cohort of patient specimens through multiplex immunofluorescence. Furthermore, we demonstrated that knocking out a key gene from the identified predictive signature in resistant organoids restored immune sensitivity and induced T-cell-mediated apoptosis. Overall, our results provide novel insights into the mechanisms underlying immunotherapy resistance and suggest new markers for enhancing patient selection. These findings may pave the way for new therapeutic options in MSS patients, potentially broadening the cohort of individuals eligible for immunotherapy.

Surgical treatment of pancreatic metastases: More appropriate surgical methods based on a clinicopathologic study of 43 patients.

There is no established surgical method for metastatic lesion to the pancreas. In the case of relatively small lesion, we often hesitate to select which surgical method, that is, wedge/partial resection or Whipple/distal pancreatectomy. Moreover, it is debatable whether lymph node dissection is necessary or not. We investigated clinicopathological characteristics in order to resolve the above problems. Forty-three patients underwent pancreatic resection formetastatic tumors in Cancer Institute of the Japanese Foundation for Cancer Research, whose specimens were investigated clinicopathologically. Primary tumors included renal cell carcinoma(RCC), colorectal carcinoma (CRC), and miscellaneous malignancy (MM) in 23, 9, and 11 cases, respectively. Plural metastases in a resected specimen or mpd, i.e., tumor extension into the main pancreatic duct (MPD) was observed in eleven (26%, 11/43) or 9 (21%, 9/43) patients, respectively. Five of 9 mpd cases had more over 2cm intraductal tumor extention from the main metastatic lesion. Lymph node metastasis surrounding the main metastasis was observed in 11 patients (5 CRCs, 5 MMs, and 1 RCC), with a metastatic rate to lymph node of 56% (5/9), 45% (5/11), and 4% (1/23) for CRCs, MMs, and RCCs, respectively. 1) Wedge or partial resection of the pancreas for metastatic tumor should not be easily chosen, because of positive resection margin due to mpd and/or leaving another metastatic lesion. 2) Lymph node dissection is not strictly necessary for the surgical removal of pancreatic metastasis from RCC, whereas this is highly recommended for patients with metastasis from CRC or MM.

Design, Synthesis and Biological Evaluation of Naphthalimide-Polyamine Conjugate as a Potential Anti-Colorectal Cancer Agent.

Colorectal cancer is the second most common cause of cancer-related death worldwide with a rising incidence, highlighting an urgent need for novel therapeutics. In this study, we developed several polyamine conjugates. Compound 6 (C6) was selected as the lead compound and was evaluated for anticancer activity in vitro and in vivo. In vitro experiments showed that C6 inhibited cell proliferation, colony formation, migration, and invasion of colorectal cancer cells while inducing apoptosis, pyroptosis, and autophagosomes formation. Genetic or pharmacological inhibition of autophagy weakened C6-induced apoptosis and gasdermin E (GSDME)-dependent pyroptosis. Inactivation of caspase 3 activity by AC-DEVD-CHO decreased the levels of N-terminal GSDME induced by C6. Furthermore, animal models exhibited suppressed tumor growth and dissemination after treatment with C6. Taken together, our findings highlight C6 as a potential drug against colorectal cancer.

Identification of Genetic Factors Related With Nonhereditary Colorectal Polyposis and Its Recurrence Through Genome-Wide Association Study.

Many patients with colorectal polyposis demonstrate negative results in germline mutation test. This study aimed to uncover genetic variants associated with nonhereditary colorectal polyposis using a genome-wide association study (GWAS). At a single referral university hospital, between January 2012 and September 2021, 638 patients with ≥ 10 biopsy-proven cumulative polyps on colonoscopy without germline mutations related to hereditary colorectal cancer or polyposis were included. The control group comprised 1863 individuals from the Korea Medical Institute, each having undergone at least two colonoscopies, all of which were normal. This study utilized GWAS to identify susceptibility loci for nonhereditary colorectal polyposis. Genetic differences between patients with and without ≥ 10 polyp recurrences were analyzed using Cox proportional hazards models. GWAS revealed 71 novel risk single-nucleotide polymorphisms (SNPs) not seen in previous colorectal cancer and polyp GWAS. Five genes (UPF3A, BICRA, CBWD6, PDE4DIP, and ABCC4) overlapping seven SNPs (rs566295755, rs2770288, rs1012003, rs201270202, rs71264659, rs1699813, and rs149368557), previously linked to colorectal cancer, were identified as significant risk factors for nonhereditary colorectal polyposis. Two novel genes (CNTN4 and CNTNAP3B), not previously associated with colorectal diseases, were identified. Three SNPs (rs149368557, rs12438834, and rs9707935) were significantly associated with higher risk of recurrence of polyposis. The gene overlapping with rs149368557 was ABCC4, which was also significantly associated with an increased risk of nonhereditary colorectal polyposis. This study identified 71 novel risk variants for nonhereditary colorectal polyposis, with three SNPs (rs149368557, rs12438834, and rs9707935) indicating significant associations with increased risk of polyposis recurrence.

NMR-based metabolomics combined with metabolic pathway analysis reveals metabolic heterogeneity of colorectal cancer tissue at different anatomical locations and stages.

Colorectal cancer (CRC) still remains the leading cause of cancer death worldwide. This study aimed to profile the metabolic differences of colorectal cancer tissues (CCT) at different stages and sites, as compared with their distant noncancerous tissues (DNT), to investigate the temporal and spatial heterogeneities of metabolic characterization. Our NMR-based metabolomics fingerprinting revealed that many of the metabolite levels were significantly altered in CCT compared to DNT and esophageal cancer tissues, indicating deregulations of glucose metabolism, one-carbon metabolism, glutamine metabolism, amino acid metabolism, fatty acid metabolism, TCA cycle, choline metabolism, and so forth. A total of five biomarker metabolites, including glucose, glutamate, alanine, valine and histidine, were identified to distinguish between early and advanced stages of CCT. Metabolites that distinguish the different anatomical sites of CCT include glucose, glycerol, glutamine, inositol, succinate, and citrate. Those significant metabolic differences in CRC tissues at different pathological stages and sites suggested temporal and spatial heterogeneities of metabolic characterization in CCT, providing a metabolic foundation for further study on biofluid metabolism in CRC early detection.

Plasma arginine as a predictive biomarker for outcomes with immune checkpoint inhibition in metastatic colorectal cancer: a correlative analysis of the CCTG CO.26 trial

BackgroundNutritional stress is a mechanism that allows tumor cells to evade the immune system. Arginine (ARG), an amino acid involved in immunomodulation, aids in regulating T-lymphocyte cell activity and the...

Plant-derived EpCAM-Fc fusion proteins induce in vivo immune response to produce IgGs inhibiting invasion and migration of colorectal cancer cells.

Transgenic tobacco plant expressed EpCAM-Fc fusion proteins to induce in vivo immune responses producing anti-EpCAM antibodies inhibiting human colorectal cancer cell invasion and migration. Plant is emerging as a promising alternative to produce valuable immunotherapeutic vaccines. In this study, we examined the in vivo anti-cancer efficacy of epidermal cell adhesion molecule (EpCAM)-Fc and EpCAM-FcK fusion proteins produced in transgenic plants as colorectal cancer vaccine candidates. Mice were injected with plant-derived EpCAM-Fc (EpCAM-FcP) and EpCAM-FcP tagged with KDEL (ER retention signal) (EpCAM-FcKP), using mammalian-derived EpCAM-Fc (EpCAM-FcM) as positive control. Total IgGs from the immunized mice were used to assess immune responses. ELISA tests revealed that IgGs from mice immunized with EpCAM-FcKP (EpCAM-FcKP IgG) exhibited the highest absorbance value for binding affinity to recombinant EpCAM-FcM compared to IgGs from mice immunized with EpCAM-FcP (EpCAM-FcP IgG) and EpCAM-FcM (EpCAM-FcM IgG). Bio-layer interferometry revealed that EpCAM-FcKP IgG had a higher affinity value than EpCAM-FcM IgG and EpCAM-FcP IgG. Cell ELISA revealed that EpCAM-FcKP IgG exhibited the highest binding activity to EpCAM-positive cells SW480 and SW620 compared to EpCAM-FcP IgG, EpCAM-FcM IgG, and anti-EpCAM mAb. In the transwell invasion assay, EpCAM-FcKP IgG significantly decreased the numbers of invaded SW480 and SW620 cells compared to EpCAM-FcP IgG, whereas EpCAM-FcM IgG had similar numbers. In the wound healing assay, EpCAM-FcKP IgG showed higher migration inhibition compared to EpCAM-FcP IgG in both cell types, with similar results to EpCAM-FcM IgG in SW620 cells. These results confirm the applicability of plant systems to produce EpCAM-Fc vaccine candidates, inducing the production of anti-EpCAM IgGs against colorectal cancer cells.

Prevalence of SPOP and IDH Gene Mutations in Prostate Cancer in a Jordanian Population.

Speckle-type POZ (SPOP) is described as an essential tumor suppressor factor in gastric cancer, colorectal cancer, and prostate cancer (PCa). SPOP gene mutations were reported in primary human PCa. Isocitrate dehydrogenase-1 (IDH1) oncogene mutations were detected in gliomas, acute myeloid leukemia, some benign and malignant cartilaginous tumors, and only 1% of PCa. This study aimed to investigate the prevalence of mutations of SPOP and IDH1 genes in PCa in the Jordanian population. One hundred formalin-fixed paraffin-embedded tissue samples were collected from patients diagnosed with prostate adenocarcinoma. The obtained specimens were subjected to genomic DNA extraction, PCR amplification, and direct sequencing of exons 4, 5, 6, and 7 of the SPOP gene and exon 6 of the IDH1 gene. SPOP gene mutations were found in 17% of PCa cases, while no mutation was detected in the screened exon 6 of the IDH1 gene. Clinicopathological data demonstrated a strong correlation between prostate-specific antigen (PSA) levels and both Gleason score (GS) and the International Society of Urological Pathology (ISUP) grade group (GG). There was no significant correlation between PSA levels and age (p = 0.816) nor there were significant associations for SPOP mutational status with age (p = 0.659), PSA levels (p = 0.395), GS (p = 0.259), and ISUP GG (p = 0.424) in the tested population. The study found a strong correlation between PSA levels and both GS and ISUP GG. It also identified a high frequency (17%) of SPOP gene mutations in Jordanian Arab PCa patients, mainly in exon 7. No IDH1 mutations were detected in exon 6.

High-resolution genetic analysis of whole APC gene deletions: a report of two cases and patient characteristics

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by germline variants in the APC gene, leading to the development of numerous colorectal polyps and significantly increases the risk of colorectal cancer. A diagnosis is typically made using colonoscopy, and genetic testing can assist in patient surveillance and carrier identification. Recent advances include the use of whole-genome array comparative genomic hybridization (a-CGH), which provides better resolution of genetic imbalances. We aimed to explore the specific features of FAP patients with whole APC gene deletions using high-resolution a-CGH and to compare patient characteristics. Two polyposis patients with whole APC deletions were identified, and the lost genetic sizes ranged from 0.3–1.1 Mb. Nervous abnormalities were a characteristic symptom in a patient with a 1.1 Mb loss. A patient with an approximately 0.3 Mb loss, which included the entire APC gene, presented a polyposis phenotype without intellectual disability. The comparison of genetic losses, with or without intellectual disability, revealed 7 genetic changes. Consequently, EPB41L4A is a candidate gene associated with the neurogenic phenotype.

The Role of Leukocyte Immunoglobulin Receptor B2 Overexpression as a Novel Biomarker and Potential Therapeutic Agent for Colorectal Cancer

The Role of Leukocyte Immunoglobulin Receptor B2 Overexpression as a Novel Biomarker and Potential Therapeutic Agent for Colorectal Cancer

Increasing Colorectal Cancer Screening in an Urban Black Community: A Pilot Randomized Clinical Trial of Multilevel Interventions.

Increasing Colorectal Cancer Screening in an Urban Black Community: A Pilot Randomized Clinical Trial of Multilevel Interventions.

A regression based approach to phylogenetic reconstruction from multi-sample bulk DNA sequencing of tumors.

DNA sequencing of multiple bulk samples from a tumor provides the opportunity to investigate tumor heterogeneity and reconstruct a phylogeny of a patient's cancer. However, since bulk DNA sequencing of tumor tissue measures thousands of cells from a heterogeneous mixture of distinct sub-populations, accurate reconstruction of the tumor phylogeny requires simultaneous deconvolution of cancer clones and inference of ancestral relationships, leading to a challenging computational problem. Many existing methods for phylogenetic reconstruction from bulk sequencing data do not scale to large datasets, such as recent datasets containing upwards of ninety samples with dozens of distinct sub-populations. We develop an approach to reconstruct phylogenetic trees from multi-sample bulk DNA sequencing data by separating the reconstruction problem into two parts: a structured regression problem for a fixed tree [Formula: see text], and an optimization over tree space. We derive an algorithm for the regression sub-problem by exploiting the unique, combinatorial structure of the matrices appearing within the problem. This algorithm has both asymptotic and empirical improvements over linear programming (LP) approaches to the problem. Using our algorithm for this regression sub-problem, we develop fastBE, a simple method for phylogenetic inference from multi-sample bulk DNA sequencing data. We demonstrate on simulated data with hundreds of samples and upwards of a thousand distinct sub-populations that fastBE outperforms existing approaches in terms of reconstruction accuracy, sample efficiency, and runtime. Owing to its scalability, fastBE enables both phylogenetic reconstruction directly from indvidual mutations without requiring the clustering of mutations into clones, as well as a new phylogeny constrained mutation clustering algorithm. On real data from fourteen B-progenitor acute lymphoblastic leukemia patients, fastBE infers mutation phylogenies with fewer violations of a widely used evolutionary constraint and better agreement to the observed mutational frequencies. Using our phylogeny constrained mutation clustering algorithm, we also find mutation clusters with lower distortion compared to state-of-the-art approaches. Finally, we show that on two patient-derived colorectal cancer models, fastBE infers mutation phylogenies with less violation of a widely used evolutionary constraint compared to existing methods.

Risk Factors for Perforation in Endoscopic Treatment for Early Colorectal Cancer: A Nationwide ENTER-K Study.

Early colorectal cancer (ECC) is commonly resected endoscopically. Perforation is a devastating complication of endoscopic resection. We aimed to identify the characteristics and predictive risk factors for perforation related to endoscopic resection of ECC. This nationwide retrospective multicenter study included patients with ECC who underwent endoscopic resection. We investigated the demographics, endoscopic findings at the time of treatment, and histopathological characteristics of the resected specimens. Logistic regression analysis was used to investigate the clinical factors associated with procedure-related perforations. Survival analysis was conducted to assess the impact of perforation on the overall survival of patients with ECC. This study included 965 participants with a mean age of 63.4 years. The most common endoscopic treatment was conventional endoscopic mucosal resection (n=573, 59.4%), followed by conventional endoscopic submucosal dissection (n=259, 26.8%). Thirty-three patients (3.4%) experienced perforations, most of which were managed endoscopically (n=23/33, 69.7%). Patients who undergo endoscopic submucosal dissection-hybrid and precut endoscopic mucosal resection have a higher risk of perforation than those who undergo conventional endoscopic mucosal resection (odds ratio, 78.65 and 39.72, p<0.05). Procedure-related perforations were not associated with patient survival. Perforation after endoscopic resection had no significant impact on the prognosis of ECC. The type of endoscopic resection was a crucial predictor of perforation. Large-scale prospective studies are needed to further investigate endoscopic resection of ECC.