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Colorectal polyps are structural abnormalities of the gastrointestinal tract that can potentially become cancerous in some cases. The study introduces a novel framework for colorectal polyp segmentation named the Multi-Scale and Multi-Path Cascaded Convolution Network (MMCC-Net), aimed at addressing the limitations of existing models, such as inadequate spatial dependence representation and the absence of multi-level feature integration during the decoding stage by integrating multi-scale and multi-path cascaded convolutional techniques and enhances feature aggregation through dual attention modules, skip connections, and a feature enhancer. MMCC-Net achieves superior performance in identifying polyp areas at the pixel level. The Proposed MMCC-Net was tested across six public datasets and compared against eight SOTA models to demonstrate its efficiency in polyp segmentation. The MMCC-Net's performance shows Dice scores with confidence interval ranging between 77.43 ± 0.12, (77.08, 77.56) and 94.45 ± 0.12, (94.19, 94.71) and Mean Intersection over Union (MIoU) scores with confidence interval ranging from 72.71 ± 0.19, (72.20, 73.00) to 90.16 ± 0.16, (89.69, 90.53) on the six databases. These results highlight the model's potential as a powerful tool for accurate and efficient polyp segmentation, contributing to early detection and prevention strategies in colorectal cancer. [ABSTRACT FROM AUTHOR]

Mitotic Arrest Deficient 1 (gene name MAD1L1), an essential component of the mitotic spindle assembly checkpoint, is frequently overexpressed in colon cancer, which correlates with poor disease-free survival. MAD1 upregulation induces two phenotypes associated with tumor promotion in tissue culture cells–low rates of chromosomal instability (CIN) and destabilization of the tumor suppressor p53. Using CRISPR/Cas9 gene editing, we generated a novel mouse model by inserting a doxycycline (dox)-inducible promoter and HA tag into the endogenous mouse Mad1l1 gene, enabling inducible expression of HA-MAD1 following exposure to dox in the presence of the reverse tet transactivator (rtTA). A modest 2-fold overexpression of MAD1 in murine colon resulted in decreased p53 expression and increased mitotic defects consistent with CIN. After exposure to the colon-specific inflammatory agent dextran sulfate sodium (DSS), 31% of mice developed colon lesions, including a mucinous adenocarcinoma, while none formed in control animals. Lesion incidence was particularly high in male mice, 57% of which developed at least one hyperplastic polyp, adenoma or adenocarcinoma in the colon. Notably, mice expressing HA-MAD1 also developed lesions in tissues in which DSS is not expected to induce inflammation. These findings demonstrate that MAD1 upregulation is sufficient to promote colon tumorigenesis in the context of inflammation in immune-competent mice. Author summary: Worldwide, colorectal cancer is the third most commonly diagnosed cancer and the second-highest cause of cancer-related deaths. A better understanding of the molecular causes of colorectal cancer could provide novel therapeutic targets for this disease. Mitotic Arrest Deficient-1 (MAD1) is commonly overexpressed in colorectal cancers, and elevated expression of MAD1 is associated with worse prognosis. Here we generated a new mutant mouse with inducible, modest overexpression of MAD1. First identified for its role in mitosis, MAD1 is required to ensure proper chromosome segregation. Elevated expression of MAD1 causes chromosome mis-segregation in the colons of these mice. During interphase, overexpressed MAD1 destabilizes the well-known tumor suppressor protein, p53. Consistent with this, mouse colons modestly overexpressing MAD1 show decreased expression of p53. Since inflammation is a risk factor for colorectal cancer, we induced inflammation in the colon using dextran sulfate sodium (DSS) and found that MAD1 overexpression significantly increased the incidence of colon tumors. Like inflammation-mediated colon tumors in humans, in the mice these tumors were more common in males than females. This work shows that MAD1 overexpression can promote colon cancer and suggests that MAD1 may be a novel drug target for this disease. [ABSTRACT FROM AUTHOR]

The influence of metabolic dysfunction-associated steatotic liver disease (MASLD) on gallbladder polyp development in both sexes remains elusive. Therefore, to clarify the role of MASLD in gallbladder polyp development, we investigated the longitudinal association between MASLD and gallbladder polyps. In this observational study, we included 5,527 gallbladder polyp-free patients who underwent > 2 health check-ups over > 2 years. Generalized estimation equations were used to analyze associations between MASLD and gallbladder polyp development according to repeated measures at baseline and the most recent stage. Gallbladder polyp development rates in men and women were 7.5% and 5.6% (p < 0.01), respectively. MASLD was not significantly correlated with gallbladder polyp development. Regarding the association between gallbladder polyp development (men: ≥6 mm and women: ≥5 mm) and the number of MASLD components following lifestyle habits, men and women with ≥ 4 MASLD components had odds ratios of 3.397 (95% confidence interval: 1.096–10.53) and 5.338 (1.054–27.04), respectively. Higher nonalcoholic fatty liver disease fibrosis scores were associated with significant risk of gallbladder polyp development in women (1.991, 1.047–3.785). Although MASLD influence on gallbladder polyp development differs by sex, close monitoring of patients with an increasing number of MASLD components is essential to prevent gallbladder polyp development. Specifically, men with ≥ 4 MASLD components should be monitored for gallbladder polyps measuring ≥ 6 mm. [ABSTRACT FROM AUTHOR]

Background: Submucosal pseudoinvasion and squamous metaplasia (SM) are incidental and special morphological findings in colorectal adenomas, and both can mimic invasive carcinoma. The coexistence of these two findings further increases the risk of misdiagnosis, posing a great diagnostic challenge to pathologists. From 1979 to 2022, only 8 cases have been reported, which was extremely rare. In this report, we presented a case of sigmoid colon adenoma accompanied by pseudoinvasion and SM. Additionally, relevant literature was analyzed to summarize the clinical and pathological characteristics. Case presentation: A 51-year-old Chinese male patient presented with fresh blood after defecation. Electronic colonoscopy revealed multiple polyps, which were removed using a snare and subjected to high-frequency electrocoagulation resection. The largest polyp, located in the sigmoid colon, was a thick pedunculated and lobulated polyp with a maximum diameter of 2.8 cm. The surface of the polyp showed slight ruggedness and redness, and it was sent for pathological examination. Grossly, the polyp had a lobulated and slightly rough surface. Microscopically, it showed a tubulovillous adenoma with focal high-grade dysplasia and mucosal muscle hyperplasia. Glandular elements were observed in the submucosal layer, forming a well-defined lobular structure. Some of the glands displayed cystic change, and focal SM could be seen within the adenoma. SM could manifest as discrete solid cell nests of varying sizes or cribriform-morular-like structures. Immunohistochemical staining showed that SM cells were diffusely positive for cytokeratin 5/6 (CK5/6); p40, p63, and cytokeratin 20 (CK20) were negative; while caudal type homeobox 2 (CDX2) was weakly positive. β-catenin showed abnormal nuclear expression, and an extremely low Ki67 proliferation index was observed. Conclusions: Coexistence of SM and pseudoinvasion in colorectal adenomas is highly rare. It is more commonly observed in males and tends to occur in the sigmoid colon. It primarily manifests in tubulovillous adenoma and tubular adenoma, with a majority of cases exhibiting a pedicle. Histologically, it is similar to invasive lesions. The cystic dilation of the submucosal glands, hemosiderin deposition, and the presence of a lamina propria around the submucosal glands without adjacent desmoplastic reaction, suggest pseudoinvasion rather than cancer. The bland cytological morphology and Immunohistochemical markers play a crucial role in distinguishing SM from true invasive lesions. [ABSTRACT FROM AUTHOR]

This study aimed to compare the microbiome profiles of patients with colorectal cancer (CRC, n =380) and colorectal adenomas (CRA, n =110) against generally healthy participants (n =2,461) from various studies. The overarching objective was to conduct a real-life experiment and develop a robust machine learning model applicable to the general population. A total of 2,951 stool samples underwent a comprehensive analysis using the in-house MetaBakery pipeline. This included various data matrices such as microbial taxonomy, functional genes, enzymatic reactions, metabolic pathways, and predicted metabolites. The study found no statistically significant difference in microbial diversity among individuals. However, distinct clusters were identified for healthy, CRC, and CRA groups through linear discriminant analysis (LDA). Machine learning analysis demonstrated consistent model performance, indicating the potential of microbiome layers (microbial taxa, functional genes, enzymatic reactions, and metabolic pathways) as prediagnostic indicators for CRC and CRA. Notable biomarkers on the taxonomy level and microbial functionality (gene families, enzymatic reactions, and metabolic pathways) associated with CRC were identified. The research presents promising avenues for practical clinical applications, with potential validation on external clinical datasets in future studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Approximately half of the populations of developed countries contract cancer, with a very high proportion of colorectal cancer among all cancer types. Food choices must be improved to maintain good health. HASPIN inhibitors suppress the proliferation of various cancer cells. In this study, the antitumor effect of ingesting bean sprouts containing the HASPIN inhibitor coumestrol was investigated using a mouse model of familial adenomatous polyposis (ApcMin/+). The results indicated that ingesting a diet including bean sprouts suppressed the development of intestinal polyps, cachexia, and hypogonadism in mice. These findings demonstrated that bean sprouts are a beneficial food for preventing cancer and are expected to be applicable in humans. (1) Background: HASPIN kinase is involved in regulating spindle function and chromosome segregation, as well as phosphorylating histone H3 at Thr3 in mitotic cells. Several HASPIN inhibitors suppress cancer cell proliferation. It was recently reported that coumestrol from bean sprouts inhibits HASPIN, and a cultivation method for bean sprouts containing large amounts of coumestrol has been established. Here, we showed the effects of bean sprout ingestion on intestinal polyp development, cachexia, and hypogonadism in a mouse model of familial adenomatous polyposis (ApcMin/+). (2) Methods: ApcMin/+ mice were randomized into control and treatment groups. Mice in the control group were given the standard diet, while those in the treatment group were given the same standard diet with the addition of 15% bean sprouts. Treatments were commenced at 7 weeks old and analyses were performed at 12 weeks old. (3) Results: ingesting bean sprouts suppressed the development of intestinal polyps, cachexia, and hypogonadism, and also increased serum levels of testosterone in male wild-type and ApcMin/+ mice. (4) Conclusions: ingesting bean sprouts helps prevent cancer and increases serum levels of testosterone in a mouse model. These results are expected to be applicable to humans. [ABSTRACT FROM AUTHOR]

To investigate the role of body mass index (BMI), serum lipid profile molecules and their derivative indexes in colorectal polyps. A total of 352 individuals who underwent colonoscopy at our center were included in this retrospective analysis. Of these, 247 patients without evident abnormalities (control group), while 105 patients diagnosed with colorectal polyps (patient group). Serum lipid profile molecules and their derivative indexes were then compared between the two groups. The patient group exhibited significantly higher levels of total cholesterol (TC) and apolipoprotein B (ApoB) compared to the control group (p<0.05). In males, the patient group displayed elevated levels of ApoB and ApoB/ApoA1 ratio compared to the control group (p<0.05). Additionally, the triglycerides (TG) and TG/high-density lipoprotein-cholesterol (HDL-C) ratios were significantly higher in the multiple polyps group than in the single polyp group (p<0.05). Furthermore, the HDL-C and HDL-C/ApoA1 ratio levels were higher in the adenomatous polyp group when compared to the non-adenomatous polyp group (p<0.05). Multiple logistic regression analysis indicated that total cholesterol (TC), TG, low-density lipoprotein-cholesterol (LDL-C), TC/HDL-C ratio, TG/HDL-C ratio and LDL-C/HDL-C ratio were risk factors for the occurrence of colorectal polyps (p<0.05). ROC curve analyses revealed that TC, ApoB, and ApoB/ApoA1 ratio were associated with colorectal polyps. No significant difference in BMI between the two groups (p>0.05). The incidence and progression of colorectal polyps are linked to serum lipid molecules and their derivative indexes. Dyslipidemia may increase the risk of colorectal polyps, potentially leading to colorectal cancer (CRC). [ABSTRACT FROM AUTHOR]

Selenium (Se), zinc (Zn), and copper (Cu) are known to be involved in carcinogenesis and participate in the defence against reactive oxygen species (ROS). This study aimed to evaluate the clinical utility of serum Se, Zn, and Cu concentrations and plasma total antioxidant status (TAS) in the diagnosis of colorectal cancer (CRC) and colorectal adenoma (CRA) in a population of low Se and borderline Zn status. Based on clinical examination and colonoscopy/histopathology, the patients (n = 79) were divided into three groups: colorectal cancer (n = 30), colorectal adenoma (n = 19), and controls (CONTROL, n = 30). The serum Se concentration was lower in the CRC group than in the CRA group (by 9.1%, p < 0.0001) and the CONTROL group (by 7.9%, p < 0.0001). In turn, the serum Zn concentration was decreased in the CRA group (by 17.9%, p = 0.019) when compared to the CONTROL group. Plasma TAS was lower in the CRC group (by 27.8%, p = 0.017) than in the CONTROL group. In turn, the serum Zn concentration was decreased in the CRA group when compared to the CONTROL group. Plasma TAS was lower in the CRC group than in the CONTROL group. ROC (receiver operating characteristic) curve analysis revealed that the Se level was of the highest diagnostic utility for the discrimination of the CRC group from both the CRA group (area under ROC curve (AUC) 0.958, sensitivity 84.21%, specificity 100%) and the CONTROL group (AUC 0.873, sensitivity 100%, specificity 66.67%). The Zn and TAS levels were significantly accurate in the differentiation between the groups. An individualised risk of colorectal adenoma and cancer approach could comprise Se, Zn, and TAS assays in the population. [ABSTRACT FROM AUTHOR]

Introduction: Nonalcoholic or metabolism-associated fatty liver disease (NAFLD or MAFLD) and colorectal polyps are chronic conditions strongly linked to lifestyle factors. However, the precise causal link between NAFLD or MAFLD and the development of colorectal polyps is not yet fully understood. This study aimed to evaluate the association between NAFLD or MAFLD and the risk of colorectal polyps based on a meta-analysis and two-sample Mendelian randomization (MR) analyses. Methods: PubMed, Embase, Cochrane Library databases were searched for eligible studies to be included in the meta-analysis. We conducted a thorough search of the PubMed, Embase, and Cochrane Library databases to identify eligible studies prior to 22 March 2024. Subgroup analyses were performed based on sex, age, and geographical region. Causality between NAFLD/MAFLD and colorectal polyps was explored by using two-sample Mendelian randomization (MR) analyses. Results: Based on an analysis of 17 studies encompassed within thismeta-analysis, a significant correlation was identified between the presence of NAFLD/MAFLD and elevated incidence of colorectal polyps (NAFLD: OR = 1.57, 95% CI: 1.43-1.73, I² = 38%, p = 0.06; MAFLD: OR = 1.67, 95% CI: 1.40-2.00, I² = 77%, p = 0.002). However, current evidence does not support a causal relationship between NAFLD/MAFLD and the prevalence of colorectal polyps (OR= 0.9998315, 95% CI: 0.9987566-1.000907, P = 0.7587638). Conclusion: NAFLD/MAFLD demonstrated a significant positive correlation with an elevated risk of developing colorectal polyps. However, the MR analysis suggested that no causal relationship existed between NAFLD/MAFLD and colorectal polyps. Therefore, further research is required to identify the underlying mechanism of causal link between these diseases. [ABSTRACT FROM AUTHOR]

This work reports the development of an electrochemical sensor using graphene-peptide conjugates for detecting colorectal cancer (CRC) biomarker leucine-rich alpha-2 glycoprotein-1 (LRG1). To enable LRG1 quantification, we rationally designed peptides with dual graphene anchoring motifs for optimal orientation and binding activity when immobilized on a reduced graphene oxide (rGO) electrochemical transducer surface. The graphene nanomaterial provides several advantages such as high conductivity, large surface area, and excellent stability that can enhance the sensor's analytical performance metrics. Furthermore, the synthetic peptides offer benefits like smaller size, specificity, ease of modification and cost-effective production compared to traditional antibody receptors. Under optimized conditions, the peptide sensor exhibited high sensitivity of 22.3 μA/(ng/mL.cm2), low limit of detection (75 pg/mL LRG1 in serum), accuracy of 101.1 % spiked recovery, and precision within 6 % RSD. Testing with colonoscopy-classified patient serum specimens discriminated normal, precancerous adenomatous polyps and malignant carcinoma stages based on LRG1 overexpression. A 24 % elevation for adenomas and 103 % higher levels in CRC were observed. Validation with spiked plasma samples indicated 97–104 % recovery and <7 % RSD, proving accurate detection capability. Comparison to antibody-based sensors showed superior linear range, sensitivity, reproducibility, and faster assay time. This demonstrates the promise of computational peptide designing combined with advanced nanomaterials for electrochemical detection of CRC progression through serum protein biomarkers. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of Angelica gigas Nakai ethanol extract (AGNEX) on benign prostatic hyperplasia (BPH) models induced by castration and testosterone propionate (TP) injection. Methods: 30 rats were randomly divided into six groups of five rats each. One group was used as a normal control (CON) and the other groups were castrated and injected intraperitoneally with TP to induce BPH. Positive control group (PCON) was administered finasteride (5 mg/kg) for 4 weeks and BPH-induced group without treatment was used as negative control (NCON). Groups administered AGNEX (1.25 mg/kg (AG1.25), 5 mg/kg (AG5), or 10 mg/kg (AG10)) instead of finasteride were assigned as study groups. The complete blood cell and lipid profiles, liver and kidney function assays, serum 5α-reductase activity and DHT levels as well as the histological examination of prostate tissues were determined. Results: The prostate volume of AG10 group decreased by approximately 35 % compared to BPH induced group (NCON). The prostate weight ratio decreased by 10 % in BPH + finasteride group compared to NCON group, and by 24 and 22 % in the AG5 and AG10 groups, respectively. AG10 group exhibited the lowest levels of 5α-reductase and dihydrotestosterone. Histopathological observations of prostate tissue showed normal cell shapes and reduced intraluminal polyp formation in the control and AGNEX-administered groups. Conclusion: The administration of 10 mg/kg of AGNEX is optimal dose for protective effect against BPH. Therefore, AGNEX has potentials for further investigations as source of lead agents for BPH management. [ABSTRACT FROM AUTHOR]

Background and Objectives: Colorectal cancer (CRC) is a heterogeneous disease of the colon or rectum arising from adenoma precursors and serrated polyps. Recently, probiotics have been proposed as an effective and potential therapeutic approach for CRC prevention and treatment. Probiotics have been shown to alleviate inflammation by restoring the integrity of the mucosal barrier and impeding cancer progression. Materials and Methods: In this study, we aimed to investigate the immunomodulatory effects of live and UV-killed Bacillus subtilis natto on the inflammatory response in CRC. Caco-2 cells were exposed to various concentrations of live and UVkilled B. subtilis natto, and cell viability was assessed using MTT assay. Gene expression analysis of IL-10, TGF-β, TLR2 and TLR4 was performed using RT-qPCR. Results: Our findings showed that both live and UV-killed B. subtilis natto caused significant reduction in inflammatory response by decreasing the gene expression of TLR2 and TLR4, and enhancing the gene expression of IL-10 and TGF-β in Caco-2 cells as compared to control group. Conclusion: The results of this study suggest that live and UV-killed B. subtilis natto may hold potential as a therapeutic supplement for modulating inflammation in CRC. [ABSTRACT FROM AUTHOR]

Specific markers for colorectal cancer (CRC), preceded by colorectal adenoma (pre-CRC), are lacking. This study aimed to investigate whether microRNAs (miR-19a-3p, miR-92a-3p, miR-193a-3p, and miR-210-3p) from tissues and exosomes are potential CRC biomarkers and compare them to existing biomarkers, namely carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9. MiRNA was isolated in the samples of 52 CRC and 76 pre-CRC patients. Expression levels were analyzed by RT-qPCR. When comparing pre-CRC and CRC tissue expression levels, only miR-193a-3p showed statistically significant result (p < 0.0001). When comparing the tissues and exosomes of CRC samples, a statistically significant difference was found for miR-193a-3p (p < 0.0001), miR-19a-3p (p < 0.0001), miR-92a-3p (p = 0.0212), and miR-210-3p (p < 0.0001). A receiver-operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to evaluate the diagnostic value of CEA, CA 19-9, and miRNAs. CEA and CA 19-9 had good diagnostic values (AUCs of 0.798 and 0.668). The diagnostic value only of miR-193a-3p was highlighted (AUC = 0.725). The final logistic regression model, in which we put a combination of CEA concentration and the miR-193a-3p expression level in tissues, showed that using these two markers can distinguish CRC and pre-CRC in 71.3% of cases (AUC = 0.823). MiR-193a-3p from tissues could be a potential CRC biomarker. [ABSTRACT FROM AUTHOR]

This article discusses a case of Muir-Torre Syndrome (MTS), a variant of hereditary non-polyposis colorectal cancer (HNPCC) syndrome, in a 46-year-old man with Fitzpatrick skin phototype V. MTS is characterized by cutaneous sebaceous tumors and keratoacanthomas, and is caused by mutations in genes involved in the mismatch repair system. The patient had a family history of HNPCC and sebaceous carcinomas, and had previously undergone genetic testing. The article describes the clinical presentation, dermoscopy findings, reflectance confocal microscopy (RCM) findings, and histopathology of the patient's lesions. It also discusses the challenges of diagnosing and differentiating sebaceoma using dermoscopy and RCM, particularly in skin of color. The authors suggest that RCM can be a useful adjunctive diagnostic tool for sebaceous tumors and call for further research on rare tumor types in skin of color. [Extracted from the article]

Coral polyps are composed of four tissues; however, their characteristics are largely unexplored. Here we report biological characteristics of tentacles (Te), mesenterial filaments (Me), body wall (Bo), and mouth with pharynx (MP), using comparative genomic, morpho-histological, and transcriptomic analyses of the large-polyp coral, Fimbriaphyllia ancora. A draft F. ancora genome assembly of 434 Mbp was created. Morpho-histological and transcriptomic characterization of the four tissues showed that they have distinct differences in structure, primary cellular composition, and transcriptional profiles. Tissue-specific, highly expressed genes (HEGs) of Te are related to biological defense, predation, and coral-algal symbiosis. Me expresses multiple digestive enzymes, whereas Bo expresses innate immunity and biomineralization-related molecules. Many receptors for neuropeptides and neurotransmitters are expressed in MP. This dataset and new insights into tissue functions will facilitate a deeper understanding of symbiotic biology, immunology, biomineralization, digestive biology, and neurobiology in corals. A draft genome and tissue-specific transcriptome assemblies of the large-polyp coral, Fimbriaphyllia ancora were established. This dataset and new insights into tissue functions will facilitate a deeper understanding of coral biology. [ABSTRACT FROM AUTHOR]

The development of premalignant colorectal polyps is significantly influenced by various lifestyle and modifiable risk factors. In our study, we used a large cohort of 9025 patients, who underwent screening colonoscopies at a university hospital, to assess the risk factors associated with the development of three different colorectal cancer precursor lesions: non-advanced adenomas (NAs), advanced adenomatous lesions (ADLs), and sessile serrated lesions (SSLs). Among the participants, 3641 had NAs, 836 had ADLs, and 533 had SSLs. We identified obesity, current smoking, and appendicular skeletal muscle mass as modifiable lifestyle risk factors that increase the development of NAs and ADLs (all P < 0.05). Furthermore, we found a positive correlation between the degree of obesity and an increased risk of developing NAs and ADLs (all P for trend < 0.001), while non-smoking was associated with a decreased risk (P for trend < 0.001 and 0.003, respectively). Smoking was the only modifiable risk factor for developing SSLs (adjusted odds ratio [aOR] 1.58; 95% confidence interval [CI] 1.20–2.07), and the risk was even higher in patients with metabolic syndrome (aOR 1.71; 95% CI 1.05–2.77). Addressing modifiable lifestyle factors such as smoking and obesity could play an important role in reducing the risk of both non-advanced and advanced adenomatous lesions. Smoking cessation is especially important as it is a significant modifiable risk factor for sessile serrated lesions. [ABSTRACT FROM AUTHOR]

Juvenile polyposis syndrome (JPS) is an inherited autosomal dominant condition that predisposes to the development of juvenile polyps throughout the gastrointestinal (GI) tract, and it poses an increased risk of GI malignancy. Germline causative variants were identified in the SMAD4 gene in a subset (20%) of JPS cases. Most SMAD4 germline genetic variants published to date are missense, nonsense, and frameshift mutations. SMAD4 germline alterations predicted to result in aberrant splicing have rarely been reported. Here, we report two unrelated Italian families harboring two different SMAD4 intronic variants, c.424+5G>A and c.425-9A>G, which are clinically associated with colorectal cancer and/or juvenile GI polyps. In silico prediction analysis, in vitro minigene assays, and RT-PCR showed that the identified variants lead to aberrant SMAD4 splicing via the exonization of intronic nucleotides, resulting in a premature stop codon. This is expected to cause the production of a truncated protein. This study expands the landscape of SMAD4 germline genetic variants associated with GI polyposis and/or cancer. Moreover, it emphasizes the importance of the functional characterization of SMAD4 splicing variants through RNA analysis, which can provide new insights into genetic disease variant interpretation, enabling tailored genetic counseling, management, and surveillance of patients with GI polyposis and/or cancer. [ABSTRACT FROM AUTHOR]

Objective: Familial adenomatous polyposis (FAP) is a genetic syndrome characterized by multiple polyps at various evolutionary stages, which, if left untreated, inevitably progress to colorectal cancer (CRC). In this study, we present a comprehensive analysis of the evolutionary history of FAP-CRC from precancerous adenoma to carcinoma. Design: Tissues were collected from gastrointestinal endoscopy or surgical resection. Exome sequencing was performed on multiple regions of adenocarcinoma (n = 8), villous adenoma (n = 10), tubular adenoma (n = 9) and blood samples were obtained from 9 patients belonging to 7 Chinese FAP families. Phylogenetic trees were reconstructed, and evolutionary analysis was conducted to reveal the temporal sequence of events leading to CRC. Results: Inherited germline mutation sites in APC gene were identified in FAP01 (p.S1281*, COSM19212), FAP03 (p.S384Tfs*19), FAP04 (p.E1538*, COSM6041693), FAP05 (p.Q1062*, COSM3696862), and FAP07-FAP09 (p.V677Sfs*3). Notably, p.V677Sfs*3 mutation was recognized as a novel germline mutation in APC, supported by evidence of genotype-phenotype correlation in pedigree analysis. Adenomas exhibited lower mutational rates than FAP-CRC and displayed recurrent alterations in well-known chromosomal instability (CIN) genes (APC, RAS, SMAD4 and TP53) and DNA damage repair genes (SUZ12, KMT2C, BCLAF1, RUNX1, and ARID1B), suggesting the presence of genomic instability. Furthermore, a progressive increase in the HRD score (a measure of "genomic scars") was observed from tubular adenomas to villous adenomas and ultimately to carcinomas. TP53 emerged as the primary driver gene for adenoma-carcinoma transition, with driver mutations consistently appearing simultaneously rather than sequentially acquired from adenomas to carcinomas. Clonal evolution demonstrated that liver metastases can originate from the same cancer-primed cell present in a primary cancerous lesion. Conclusion: We identified a novel pathogenic variant in APC, namely, p.V677Sfs*3. The process of carcinogenesis in FAP-CRC supports the classical cancerization model, where an initial APC mutation leads to the activation of the WNT signaling pathway and CIN. Subsequently, additional mutations occur in other putative CIN genes (e.g., DNA repair, chromatin remodeling), ultimately leading to the development of microsatellite stable (MSS) tumors. Our study provides a comprehensive understanding of the genomic landscapes that underlie the transition from adenoma to carcinoma. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a common digestive system tumor with high morbidity and mortality worldwide. At present, the use of computer-assisted colonoscopy technology to detect polyps is relatively mature, but it still faces some challenges, such as missed or false detection of polyps. Therefore, how to improve the detection rate of polyps more accurately is the key to colonoscopy. To solve this problem, this paper proposes an improved YOLOv5-based cancer polyp detection method for colorectal cancer. The method is designed with a new structure called P-C3 incorporated into the backbone and neck network of the model to enhance the expression of features. In addition, a contextual feature augmentation module was introduced to the bottom of the backbone network to increase the receptive field for multi-scale feature information and to focus on polyp features by coordinate attention mechanism. The experimental results show that compared with some traditional target detection algorithms, the model proposed in this paper has significant advantages for the detection accuracy of polyp, especially in the recall rate, which largely solves the problem of missed detection of polyps. This study will contribute to improve the polyp/adenoma detection rate of endoscopists in the process of colonoscopy, and also has important significance for the development of clinical work. [ABSTRACT FROM AUTHOR]

We have previously identified increased levels of distinct bacterial taxa within mucosal biopsies from colorectal cancer (CRC) patients. Following prior research, the aim of this study was to investigate the detection of the same CRC‐associated bacteria in fecal samples and to evaluate the suitability of fecal samples as a non‐invasive material for the detection of CRC‐associated bacteria. Next‐generation sequencing (NGS) of the 16S ribosomal RNA (rRNA) V4 region was performed to evaluate the detection of the CRC‐associated bacteria in the fecal microbiota of cancer patients, patients with adenomatous polyp and healthy controls. Furthermore, 19 novel species‐specific quantitative PCR (qPCR) assays were established to detect the CRC‐associated bacteria. Approximately, 75% of the bacterial taxa identified in biopsies were reflected in fecal samples. NGS failed to detect low‐abundance CRC‐associated taxa in fecal samples, whereas qPCR exhibited high sensitivity and specificity in identifying all targeted taxa. Comparison of fecal microbial composition between the different patient groups showed enrichment of Fusobacterium nucleatum, Parvimonas micra, and Gemella morbillorum in cancer patients. Our findings suggest that low‐abundance mucosa‐associated bacteria can be detected in fecal samples using sensitive qPCR assays. [ABSTRACT FROM AUTHOR]

Introduction: Although the incidence and mortality rates of colorectal cancer exhibit significant variability, it remains one of the most prevalent cancers worldwide. Endeavors to prevent colorectal cancer development focus on detecting precursor lesions during colonoscopy. The diagnosis of endoscopically resected polyps relies on hematoxylin and eosin staining examination. For challenging cases like adenomatous polyps with epithelial misplacement, additional diagnostic methods could prove beneficial. Methods: This paper aims to underscore stromal changes observed in malignant polyps and polyps with pseudoinvasion, leveraging two-photon excitation microscopy (TPEM), a technique extensively employed in the medical field in recent years. Results and discussions: Both the subjective and quantitative analysis of TPEM images revealed distinct distributions and densities of collagen at the invasion front in malignant polyps compared to areas of pseudoinvasion. TPEM holds potential in discerning true invasion in malignant polyps from pseudoinvasion, offering enhanced visualization of local stromal changes. [ABSTRACT FROM AUTHOR]

Objectives: Adrenocortical carcinoma (ACC), a rare and aggressive adrenal cortex cancer, poses significant challenges due to high mortality, poor prognosis, and early post-surgery recurrence. Variability in survival across ACC stages emphasizes the need to uncover its molecular underpinnings. Adrenocortical adenoma, a benign tumor, adds to diagnostic challenges, highlighting the necessity for molecular insights. The Non-SMC Associated Condensin Complex (NCAP) gene family, recognized for roles in chromosomal structure and cell cycle control. This study focuses on evaluating NCAP gene functions and importance in ACC through gene expression profiling to identify diagnostic and therapeutic targets. Methods: Microarray datasets from ACC patients, obtained from the Gene Expression Omnibus database, were normalized to eliminate batch effects. Differential expression analysis of NCAP family genes, facilitated by the GEPIA2 database, included survival and pathological stage evaluations. A Protein-Protein Interaction network was constructed using GeneMANIA, and additional insights were gained through Gene Ontology enrichment analysis, correlation analysis, and ROC curve analysis. Results: ACC samples exhibited elevated levels of NCAPG, NCAPG2, and NCAPH compared to normal and adenoma samples. Increased expression of these genes correlated with poor overall survival, particularly in advanced disease stages. The Protein-Protein Interaction network highlighted interactions with related proteins, and Gene Ontology enrichment analysis demonstrated their involvement in chromosomal structure and control. Differentially expressed NCAP genes showed positive associations, and ROC curve analysis indicated their high discriminatory power in identifying ACC from adenoma and normal samples. Conclusion: The study emphasizes the potential importance of NCAPG, NCAPG2, and NCAPH in ACC, suggesting roles in tumor aggressiveness and diagnostic relevance. These genes could serve as therapeutic targets and markers for ACC, but further exploration into their molecular activities and validation studies is imperative to fully harness their diagnostic and therapeutic potential, advancing precision medicine approaches against this rare but lethal malignancy. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is a significant health issue, with notable incidence rates in Norway. The immune response plays a dual role in CRC, offering both protective effects and promoting tumor growth. This research aims to provide a detailed screening of immune-related genes and identify specific genes in CRC and adenomatous polyps within the Norwegian population, potentially serving as detection biomarkers. Methods: The study involved 69 patients (228 biopsies) undergoing colonoscopy, divided into CRC, adenomatous polyps, and control groups. We examined the expression of 579 immune genes through nCounter analysis emphasizing differential expression in tumor versus adjacent non-tumorous tissue and performed quantitative reverse transcription polymerase chain reaction (RT-qPCR) across patient categories. Results: Key findings include the elevated expression of CXCL1, CXCL2, IL1B, IL6, CXCL8 (IL8), PTGS2, and SPP1 in CRC tissues. Additionally, CXCL1, CXCL2, IL6, CXCL8, and PTGS2 showed significant expression changes in adenomatous polyps, suggesting their early involvement in carcinogenesis. Conclusions: This study uncovers a distinctive immunological signature in colorectal neoplasia among Norwegians, highlighting CXCL1, CXCL2, IL1B, IL6, CXCL8, PTGS2, and SPP1 as potential CRC biomarkers. These findings warrant further research to confirm their role and explore their utility in non-invasive screening strategies. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Colonoscopy is the primary method to prevent CRC. However, traditional polyp detection methods face problems such as low image resolution and the possibility of missing polyps. In recent years, deep learning techniques have been extensively employed in the detection of colorectal polyps. However, these algorithms have not yet addressed the issue of detection in low-resolution images. In this study, we propose a novel YOLO-SRPD model by integrating SRGAN and YOLO to address the issue of low-resolution colonoscopy images. Firstly, the SRGAN with integrated ACmix is used to convert low-resolution images to high-resolution images. The generated high-resolution images are then used as the training set for polyp detection. Then, the C3_Res2Net is integrated into the YOLOv5 backbone to enhance multiscale feature extraction. Finally, CBAM modules are added before the prediction head to enhance attention to polyp information. The experimental results indicate that YOLO-SRPD achieves a mean average precision (mAP) of 94.2% and a precision of 95.2%. Compared to the original model (YOLOv5), the average accuracy increased by 1.8% and the recall rate increased by 5.6%. These experimental results confirm that YOLO-SRPD can address the low-resolution problem during colorectal polyp detection and exhibit exceptional robustness. [ABSTRACT FROM AUTHOR]

Background: Early detection of colorectal neoplasms can reduce the colorectal cancer (CRC) burden by timely intervention for high-risk individuals. However, effective risk prediction models are lacking for personalized CRC early screening in East Asian (EAS) population. We aimed to develop, validate, and optimize a comprehensive risk prediction model across all stages of the dynamic adenoma-carcinoma sequence in EAS population. Methods: To develop precision risk-stratification and intervention strategies, we developed three trans-ancestry PRSs targeting colorectal neoplasms: (1) using 148 previously identified CRC risk loci (PRS148); (2) SNPs selection from large-scale meta-analysis data by clumping and thresholding (PRS183); (3) PRS-CSx, a Bayesian approach for genome-wide risk prediction (PRSGenomewide). Then, the performance of each PRS was assessed and validated in two independent cross-sectional screening sets, including 4600 patients with advanced colorectal neoplasm, 4495 patients with non-advanced adenoma, and 21,199 normal individuals from the ZJCRC (Zhejiang colorectal cancer set; EAS) and PLCO (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; European, EUR) studies. The optimal PRS was further incorporated with lifestyle factors to stratify individual risk and ultimately tested in the PLCO and UK Biobank prospective cohorts, totaling 350,013 participants. Results: Three trans-ancestry PRSs achieved moderately improved predictive performance in EAS compared to EUR populations. Remarkably, the PRSs effectively facilitated a thorough risk assessment across all stages of the dynamic adenoma-carcinoma sequence. Among these models, PRS183 demonstrated the optimal discriminatory ability in both EAS and EUR validation datasets, particularly for individuals at risk of colorectal neoplasms. Using two large-scale and independent prospective cohorts, we further confirmed a significant dose–response effect of PRS183 on incident colorectal neoplasms. Incorporating PRS183 with lifestyle factors into a comprehensive strategy improves risk stratification and discriminatory accuracy compared to using PRS or lifestyle factors separately. This comprehensive risk-stratified model shows potential in addressing missed diagnoses in screening tests (best NPV = 0.93), while moderately reducing unnecessary screening (best PPV = 0.32). Conclusions: Our comprehensive risk-stratified model in population-based CRC screening trials represents a promising advancement in personalized risk assessment, facilitating tailored CRC screening in the EAS population. This approach enhances the transferability of PRSs across ancestries and thereby helps address health disparity. [ABSTRACT FROM AUTHOR]

Background: Pituitary adenomas comprise clinical and pathological characteristics of functional and non-functional subtypes. To enhance our understanding of diagnostic presentations, our study aimed to know the clinicopathological characteristics of pituitary adenomas of both functional and non-functional subtypes. The purpose of our study was to investigate the clinicopathological characteristics of pituitary adenomas, including demographic characteristics, clinical presentations, hormone secretion patterns, invasiveness, and cellular characteristics. Methods: A total of 41 cases of pituitary adenomas were analyzed, with 63.4% classified as non-functional adenomas (NFPA) and 36.6% as functional adenomas (FPA). Clinical presentations vary, with vision loss and headaches commonly occurring in both NFPA and FPA. In FPAs, serum hormone levels varied and were categorized into growth hormone-secreting (53.3%), ACTH-secreting (26.7%), PRL-secreting (13.3%), and FSH-secreting (6.7%) subtypes. Moreover, clinical presentations in FPA included diplopia, giddiness, vomiting, ptosis, and limb weakness. Clinical features varied across subtypes, with acromegaly in growth hormone-secreting adenomas, moon facies and weight gain in ACTH-secreting adenomas, poor facial growth in PRL-secreting adenomas, and vision loss in FSH-secreting adenomas. Meanwhile, NFPA were predominantly macroadenomas (88.5%) and exhibited various morphological patterns. Results: The proliferation index is higher in functional adenomas (mean 1.32) as compared to non-functional (mean 0.91). Clinical presentations varied across functional and non-functional adenomas. Growth hormone-secreting adenomas were the most common functional subtype, while LH and null cell adenomas were common non-functional subtypes. Two cases were invasive adenomas with a low Ki67 index. Sheets were the most common morphological pattern. PCA analysis revealed significant differences between the two groups, with PC 1 explaining 92.111% of the variance. Conclusions: Our study elucidates the clinicopathological characteristics of pituitary adenomas, highlighting significant differences between functional and non-functional subtypes. These findings underscore the importance of tailored diagnostic and management strategies to optimize outcomes for patients with pituitary adenomas. [ABSTRACT FROM AUTHOR]

Background: PolyDeep is a computer-aided detection and classification (CADe/x) system trained to detect and classify polyps. During colonoscopy, CADe/x systems help endoscopists to predict the histology of colonic lesions. Objective: To compare the diagnostic performance of PolyDeep and expert endoscopists for the optical diagnosis of colorectal polyps on still images. Methods: PolyDeep Image Classification (PIC) is an in vitro diagnostic test study. The PIC database contains NBI images of 491 colorectal polyps with histological diagnosis. We evaluated the diagnostic performance of PolyDeep and four expert endoscopists for neoplasia (adenoma, sessile serrated lesion, traditional serrated adenoma) and adenoma characterization and compared them with the McNemar test. Receiver operating characteristic curves were constructed to assess the overall discriminatory ability, comparing the area under the curve of endoscopists and PolyDeep with the chi- square homogeneity areas test. Results: The diagnostic performance of the endoscopists and PolyDeep in the characterization of neoplasia is similar in terms of sensitivity (PolyDeep: 89.05%; E1: 91.23%, p=0.5; E2: 96.11%, p<0.001; E3: 86.65%, p=0.3; E4: 91.26% p=0.3) and specificity (PolyDeep: 35.53%; E1: 33.80%, p=0.8; E2: 34.72%, p=1; E3: 39.24%, p=0.8; E4: 46.84%, p=0.2). The overall discriminative ability also showed no statistically significant differences (PolyDeep: 0.623; E1: 0.625, p=0.8; E2: 0.654, p=0.2; E3: 0.629, p=0.9; E4: 0.690, p=0.09). In the optical diagnosis of adenomatous polyps, we found that PolyDeep had a significantly higher sensitivity and a significantly lower specificity. The overall discriminative ability of adenomatous lesions by expert endoscopists is significantly higher than PolyDeep (PolyDeep: 0.582; E1: 0.685, p < 0.001; E2: 0.677, p < 0.0001; E3: 0.658, p < 0.01; E4: 0.694, p < 0.0001). Conclusion: PolyDeep and endoscopists have similar diagnostic performance in the optical diagnosis of neoplastic lesions. However, endoscopists have a better global discriminatory ability than PolyDeep in the optical diagnosis of adenomatous polyps. [ABSTRACT FROM AUTHOR]

Background: The dysregulation of gene expression is one of the key molecular features of colorectal cancer (CRC) development. This study aimed to investigate whether such dysregulation is reflected in rectal swab specimens of CRC patients and to evaluate its potential as a non-invasive approach for screening. Methods: We compared the expression level of 14 CRC-associated genes in tumor and adjacent non-tumor tissue of CRC patients and examined the correlation of their levels in tissue with paired rectal swab specimens. The level of these 14 genes in rectal swab specimens was compared among patients with CRC or polyp and control subjects, and the diagnostic potential of each dysregulated gene and the gene panel were evaluated. Results: The expression of CXCR2, SAA, COX1, PPARδ, PPARγ, Groγ, IL8, p21, c-myc, CD44 and CSF1 was significantly higher in CRC, and there was a significant correlation in the levels of most of them between the CRC and rectal swab specimens. In the training study, we showed that CD44, IL8, CXCR2 and c-myc levels were significantly higher in the rectal swab specimens of the CRC patients. Such result was confirmed in the validation study. A panel of these four genes was developed, and ROC analysis showed that this four-gene panel could identify CRC patients with an AUC value of 0.83 and identify overall polyp and precancerous adenoma patients with AUC values of 0.6522 and 0.7322, respectively. Finally, the predictive study showed that the four-gene panel demonstrated sensitivities of 63.6%, 76.9% and 88.9% in identifying overall polyp, precancerous adenoma and CRC patients, respectively, whereas the specificity for normal subjects was 72.2%. Conclusion: The expression of CRC-associated genes in rectal swab specimens reflects the dysregulation status in colorectal tissue, and the four-gene panel is a potential non-invasive biomarker for early precancerous adenoma and CRC screening. [ABSTRACT FROM AUTHOR]

Patients with familial adenomatous polyposis (FAP) develop early colorectal adenomas and if left untreated, progression to cancer is an inevitable event. Prophylactic surgery does not prevent further development of cancer in the rectal remnant, rectal cuff in patients with ileal pouch anal anastomosis (IPAA) and even on the ileal mucosa of the pouch body. The aim of this review is to assess long-term rates of cancer and adenoma development in patients with FAP after prophylactic surgery and to summarise current recommendations for endoscopic management and surveillance of these patients. A systematic literature search of studies from January 1946 through to June 2023 was conducted using the PRISMA checklist. The electronic database PubMed was searched. Fifty-four papers involving 5010 patients were reviewed. Cancer rate in the rectal remnant was 8.8–16.7% in the western population and 37% in the eastern population. The cumulative risk of cancer 30 years after surgery was 24%. Mortality due to cancer in the rectal remnant is 1.1–11.1% with a 5-year survival rate of 55%. The adenoma rate after primary IPAA was 9.4–85% with a cumulative risk of 85% 20 years after surgery and a cumulative risk of 12% for advanced adenomas 10 years after surgery. Cumulative risk for adenomas after ileorectal anastomosis (IRA) was 85% after 5 and 100% after 10 years. Adenomas developed more frequently after stapled (33.9–57%) compared to hand-sewn (0–33%) anastomosis. We identified reports of 45 cancers in patients after IPAA of which 30 were in the pouch body and 15 in the rectal cuff or at the anastomosis. There was a significant incidence of cancer and adenomas in the rectal remnant and ileal pouch of FAP patients during the long-term follow-up. Regular endoscopic surveillance is recommended, not only in IRA patients, but also in pouch patients after proctocolectomy. [ABSTRACT FROM AUTHOR]

Colorectal cancer is currently a public health concern due to its high incidence, morbidity, and mortality rates. Researchers have identified the intestinal microbiome as a crucial factor in the development of this disease. Currently, specialized literature data support the role of the microbiota in both the development of colorectal cancer and resistance to oncological therapies. Therefore, studying the composition of the gut microbiome can aid in creating risk assessment tools to identify specific populations that would benefit from tailored screening approaches. Also, manipulation of the intestinal microbiome can be useful in improving the response to chemotherapy or immunotherapy. Identifying the pathogenic mechanisms responsible for this causal link can aid in the discovery of novel treatment targets. This article will provide the latest information regarding the influence of the intestinal microbiota on the development and progression of colorectal cancer. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) outcomes in terms of incidence and mortality are significantly worse in African Americans than other Americans. While differences in primary preventions for neoplasia (diet, obesity remediation, aspirin prophylaxis) are being elucidated, genetic mutations affecting premalignant lesions and immune response mechanisms may possibly also explain the increased incidence and mortality, particularly from right-sided disease. Objective: Our team therefore examined colonic segments seeking to test the hypothesis that the immune response and somatic genetic profiles of the colonic anatomic segments may vary and thus account for variations in neoplasia risk among the various colonic segments revealing an antigenic relationship with precancerous lesions. The p87 antigenic field effect is recognized via Adnab-9 antibody immunohistochemistry to be significantly less in the right colon in African Americans, particularly in the cecum. Method: Since small high-grade dysplastic adenomas (SHiGDA) likely missed by CRC screening may progress to cancer, we used Ion Torrent™ sequencing of DNA extracted from four normal colonic segments (two left-sided and two right) of patients with SHiGDAs. We also contrasted unique mutational fields in one patient with a large HiGDA (APC with unique mutations) and one patient who prospectively developed a SHiGDA (JAK3). Result: The SHiGDA (small high-grade dysplastic polyp) patient was p87 negative for any extracted stool, saliva, or colonic effluent via ELISA (enzyme linked immunoadsorbant assay). Furthermore, mean values of expression in segments from the right colon were reduced with respect to the means obtained from the left segments in 233 patients evaluated for a p87 field effect. This has recently been shown to be the case in a large cohort of AA and Caucasian 2294 patients, possibly explaining the right-sided CRC disparity in African Americans and the subsequent increase in mortality. This field effect disparity is also true for two cancers contracted by the SHiGDa patient (lung and prostate). Conclusion: Thus, this pilot study suggests that the reduction in p87 in the right colon is possibly correlated with JAK3 mutations. If confirmed, JAK3 mutations, known to be associated with immune aberrations, may provide a mechanistic explanation for the lack of a p87 (protein 87 kilodaltons) field in some patients with HGD polyps who might benefit from possible intervention such as more intensive screening. Limited microbiome studies were also performed on two patients with familial cancer syndromes and these compared favorably with controls available from the literature. [ABSTRACT FROM AUTHOR]