Colonic Tubular Adenoma with Clear Cell Change: Case Report with Whole-Exome Sequencing and Updated Review of the Literature.

INTRODUCTION: Colorectal tubular adenomas displaying clear cell change are rare entities, with unknown clinical relevance, prognosis, immunohistochemical, and molecular features. CASE PRESENTATION: Hereby we report a case of a 43-year-old female patient with a rectosigmoid polyp. Histologically, conventional dysplasia was visible with scattered areas displaying clear cell change. Whole-exome sequencing (WES) was carried out and revealed high tumour mutation burden and 7 pathogenic mutations, including TP53, APC, FGFR4, EHBP1, IL4R, TYR, and ACTN3. CONCLUSION: Clear cell change may only be present in less than 0.1% of adenomas. Aetiology is not well understood; additionally, few authors suggest autolysis or fixation problems. Our WES resulted in newly found pathogenic mutations, and high mutation burden, proving the lesion's neoplastic origin. Hitherto, neither special stainings nor immunohistochemical markers proved to be useful in the diagnostic process. From a differential diagnostic perspective, enteroblastic differentiation, primary and secondary clear cell adenocarcinoma has to be excluded.

Proteome analysis of formalin-fixed paraffin-embedded colorectal adenomas reveals the heterogeneous nature of traditional serrated adenomas compared to other colorectal adenomas.

Traditional serrated adenoma (TSA) remains the least understood of all the colorectal adenomas, although these lesions have been associated with a significant cancer risk, twice that of the conventional adenoma (CAD) and of the sessile serrated adenoma (SSA/P). This study was performed to investigate the proteomic profiles of the different colorectal adenomas to better understand the pathogenesis of TSA. We performed a global quantitative proteome analysis using the label-free quantification (LFQ) method on 44 colorectal adenoma (12 TSAs, 15 CADs, and 17 SSA/Ps) and 17 normal colonic mucosa samples, archived as formalin-fixed paraffin-embedded blocks. Unsupervised consensus hierarchical clustering applied to the whole proteomic profile of the 44 colorectal adenomas identified four subtypes: C1 and C2 were well-individualized clusters composed of all the CADs (15/15) and most of the SSA/Ps (13/17), respectively. This is consistent with the fact that CADs and SSA/Ps are homogeneous and distinct colorectal adenoma entities. In contrast, TSAs were subdivided into C3 and C4 clusters, consistent with the more heterogeneous entity of TSA at the morphologic and molecular levels. Comparison of the proteome expression profile between the adenoma subtypes and normal colonic mucosa further confirmed the heterogeneous nature of TSAs, which overlapped either on CADs or SSA/Ps, whereas CADs and SSAs formed homogeneous and distinct entities. Furthermore, we identified LEFTY1 a new potential marker for TSAs that may be relevant for the pathogenesis of TSA. LEFTY1 is an inhibitor of the Nodal/TGFß pathway, which we found to be one of the most overexpressed proteins specifically in TSAs. This finding was confirmed by immunohistochemistry. Our study confirms that CADs and SSA/Ps form homogeneous and distinct colorectal adenoma entities, whereas TSAs are a heterogeneous entity and may arise from either SSA/Ps or from normal mucosa evolving through a process related to the CAD pathway. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Fecal microbiota changes with fermented kimchi intake regulated either formation or advancement of colon adenoma.

Gut bacteria might contribute in early stage of colorectal cancer through the development and advancement of colon adenoma, by which exploring either beneficial bacteria, which are decreased in formation or advancement of colon adenoma and harmful bacteria, which are increased in advancement of colon adenoma may result in implementation of dietary interventions or probiotic therapies to functional means for prevention. Korean fermented kimchi is one of representative probiotic food providing beneficiary microbiota and exerting significant inhibitory outcomes in both APC/Min+ polyposis model and colitis-associated cancer. Based on these backgrounds, we performed clinical trial to document the changes of fecal microbiota in 32 volunteers with normal colon, simple adenoma, and advanced colon adenoma with 10 weeks of fermented kimchi intake. Each amplicon is sequenced on MiSeq of Illumina and the sequence reads were clustered into Operational Taxonomic Units using VSEARCH and the Chao Indices, an estimator of richness of taxa per individual, were estimated to measure the diversity of each sample. Though significant difference in α or ß diversity was not seen between three groups, kimchi intake significantly led to significant diversity of fecal microbiome. After genus analysis, Acinobacteria, Cyanobacteria, Clostridium sensu, Turicibacter, Gastronaeophillales, H. pittma were proven to be increased in patients with advanced colon adenoma, whereas Enterococcua Roseburia, Coryobacteriaceau, Bifidobacterium spp., and Akkermansia were proven to be significantly decreased in feces from patients with advanced colon adenoma after kimchi intake. Conclusively, fermented kimchi plentiful of beneficiary microbiota can afford significant inhibition of either formation or advancement of colon adenoma.

Rate of colorectal neoplasia in patients with Hodgkin lymphoma.

AIM: Survivors of Hodgkin lymphoma (HL) are at increased risk of breast, lung, thyroid, stomach, pancreatic and colon cancer. There is limited information on the utility of endoscopic screening for colon cancer. We aimed to describe the adenoma detection rate (ADR) in patients with HL to determine the appropriate timing of colonoscopy screening. METHOD: We retrospectively studied patients with HL who underwent colonoscopy between 2000 and 2017. RESULTS: A total of 251 patients underwent colonoscopy. Eighty (32%) patients had 151 colonic polyps. Thirty per cent of the polyps exhibited high-grade dysplasia, and invasive colon adenocarcinoma was found in 10 patients. Patients with the nodular sclerosing subtype of HL had a significantly lower ADR than others (P = 0.002). The ADR was 5% in patients younger than 35 years (n = 64), 23% in patients between 35 and 40 years of age (n = 22), 39% in patients between 40 and 50 years of age (n = 51) and 46% in patients older than 50 years (n = 114).

A novel technique of endoscopic submucosal dissection for circumferential ileocecal valve adenomas with terminal ileum involvement: the "doughnut resection" (with videos).

BACKGROUND: Ileocecal valve (ICV) lesions are difficult to resect endoscopically and patients are often referred for laparoscopic colectomy. ICV involvement has been shown to be related to technical failure and tumor recurrence after endoscopic mucosal resection (EMR) and represents a challenge for endoscopic submucosal dissection (ESD). Few publications have focused specifically on endoscopic management of ICV lesions. METHODS: We developed a novel ESD technique, the "doughnut resection," for circumferential ICV adenomas with terminal ileum involvement. Two circumferential mucosal incisions are performed, one in the ileum and the other in the cecum, followed by submucosal dissection of the disk of tissue between the two incisions around a guiding stent placed across the valve that helps guide the dissection as it crosses the valve orifice. The lesion is removed en bloc in the shape of a "doughnut" with two concentric assessable lateral margins. The underwater ESD technique and a gastroscope were used to facilitate the resection. RESULTS: Seven patients received the doughnut resection. The median patient age was 67 years. All patients had prior biopsy and three had prior endoscopic resection (1-6 times). The median specimen diameter was 4.5 cm (range 3-8). All resections were en bloc and R0. There was no perforation, delayed bleeding, or other clinically significant adverse events. After a median follow-up of 21 months (range 12-32), there was no tumor recurrence. CONCLUSION: The "doughnut resection" is a feasible, safe, and effective method to remove circumferential ICV lesions endoscopically even for patients with multiple prior tumor manipulations.

A risk-prediction model for en bloc resection failure or perforation during endoscopic submucosal dissection of colorectal neoplasms.

OBJECTIVES: Technical difficulties in colorectal endoscopic submucosal dissections (ESD) result in en bloc resection failure or perforation. This study aimed to develop and validate a risk score for predicting en bloc resection failure or perforation in ESD of colorectal neoplasms. METHODS: This single-center observational study included 1133 colorectal neoplasms treated with ESD in a Japanese tertiary cancer center. With a derivation set (n = 716), we performed multiple logistic regression to identify significant risk factors for en bloc resection failure or perforation. Based on odds ratios, we developed a risk score, ranging from 0 to 10: 0-1 'low risk' (LR); 2-4 'moderate risk' (MR); and 5-10 'high risk' (HR). An independent validation set comprised prospectively enrolled subjects (n = 417) that underwent ESDs from January 2014 to August 2016. The performance of the risk score for predicting en bloc resection failure or perforation for each risk tier was evaluated. RESULTS: The baseline incidences of en bloc resection failure or perforation were 14.5% and 5.5% in the derivation and validation sets, respectively. We identified the following significant risk factors: endoscopist experience, tumor location, morphology, scope operability, underlying fold, and fold convergence. In the validation set, the incidences of en bloc resection failure or perforation were 0% in the LR tier (n = 62; 14.8%), 2.3% in the MR tier (n = 293; 70.4%), and 25.8% in the HR tier (n = 62; 14.8%) (P < 0.001, Cochran-Armitage trend test). CONCLUSIONS: A risk scoring system, which was developed and prospectively validated, can successfully estimate the incidence of en bloc resection failure or perforation.

Patients with Non-Hodgkin's Lymphoma Are at Risk of Adenomatous Colon Polyps.

BACKGROUND: Patients with non-Hodgkin's lymphoma (NHL) are frequently referred for colonoscopy to evaluate gastrointestinal symptoms during their treatment course. Here, we described the rate of colonic adenomas in patients with NHL. METHODS: This was a retrospective study of patients with NHL who underwent colonoscopy after being diagnosed with NHL between January 2000 and December 2017. RESULTS: Of the 17,938 patients who had been diagnosed with NHL in the study period, 2176 met the inclusion criteria. The mean age at the time of colonoscopy was 61 years. Most patients were male (61%). Overall, 1273 polyps were detected in 811 patients (37%). Sessile serrated adenomas were detected in 102 (5%) patients. The overall ADR was 12% in patients younger than 40 years of age (n = 103), 26% in patients aged 40-50 (n = 251), 34% in patients aged 51-60 (n = 630), and 43% in patients older than 60 (n = 1212). Most polyps were located in the right colon (63%), and 101 (8%) were larger than 1 cm. Villous adenomatous features were present in 1% of polyps, while high-grade dysplasia was detected in 22%. Invasive adenocarcinoma was identified in 4%. The median interval from lymphoma diagnosis to adenoma detection was 1.4 years (interquartile range 0.5-3.8 years). A repeat colonoscopy was performed in 343 patients. The overall ADR on repeat colonoscopy was 30%. Cox regression analysis revealed that age (hazards ratio 1.04; 95% confidence interval 1.03-1.05; P < 0.001) and male sex (hazards ratio 1.35; 95% confidence interval 1.13-1.60; P = 0.001) were independent factors associated with worse overall survival. By contrast, screening colonoscopy was associated with longer survival duration (hazards ratio 0.48; 95% confidence interval 0.36-0.63; P < 0.001). CONCLUSION: The ADR in NHL patients aged 40-50 years was equivalent to that reported in the literature in non-cancer patients aged 50-70 years. Early screening colonoscopy may be warranted in NHL patients younger than 50 years. Screening colonoscopy significantly improved the overall survival of patients with NHL.

GPNMB methylation: a new marker of potentially carcinogenic colon lesions.

BACKGROUND: Epigenetic plays an important role in colorectal neoplasia process. There is a need to determine sound biomarkers of colorectal cancer (CRC) progression with clinical and therapeutic implications. Therefore, we aimed to examine the role and methylation status of Glyco Protein Non-Metastatic GPNM B (GPNMB) gene in normal, adenoma and CRC in African American (AA) patients. METHODS: The methylation status of 13 CpG sites (chr7: 23287345-23,287,426) in GPNMB gene's promoter, was analyzed by pyrosequencing in human CRC cell lines (HCT116, SW480, and HT29) and microdissected African American paraffin embedded samples (20 normal, 21 non-advanced adenoma (NA), 48 advanced adenoma (AD), and 20 cancer tissues. GPNMB expression was analyzed by immunohistochemistry (IHC) on tissue microarrays (TMA). Correlations between GPNMB methylation and expression with clinicopathological features were analyzed. GPNMB functional analysis was performed in triplicates using cell proliferation, migration and invasion assays in HCT116 colon cell line after stable transfection with a GPNMB-cDNA expression vector. RESULTS: GPNMB methylation was lower in normal mucosa compared to CRC samples (1/20 [5%] vs. 18/20 [90%]; P < 0.001). AD also had a significantly higher GPNMB methylation frequency than normal colon samples (42/48 [88%] vs 1/20 [5%]; P < 0.001). GPNMB was more frequently methylated in AD than in matched normal mucosa from three patients (3/3 [100%] vs 1/3 [33.3%]; P < 0.001). The frequency of GPNMB methylation in NA differed significantly from that in the normal mucosa (16/21 [76%] vs 1/20 [5%]; P = 0.008). There was statistically significant correlation of higher methylation at advanced stages and lower methylation at stage 1 CRCs (P < 0.05). In agreement with these findings, GPNMB protein expression decreased in CRC tissues compared with AD and NA colon mucosa (p < 0.05). GPNMB overexpression in HCT116 colon cancer cell line decreased cell proliferation [(24 h, P = 0.02), (48 h, P < 0.001, 72 h, P = 0.007)], invasion (p < 0.05) and migration (p > 0.05) compared to the mock-transfected cells. CONCLUSION: Our data indicate a high methylation profile leading to a lower GPNMB expression in adenoma and CRC samples. The functional analysis established GPNMB as a potential tumor suppressor gene. As such, GPNMB might be useful as a biomarker of adenomas with high carcinogenic potential.

Feasibility of CYFRA 21-1 as a serum biomarker for the detection of colorectal adenoma and advanced colorectal adenoma in people over the age of 45.

BACKGROUND: Colon adenoma (CA) is a premalignant lesion of colorectal cancer, and its early removal is closely associated with more prolonged survival in the general population. In this study, we aimed to evaluate the relationship between diverse biologic markers and a newly diagnosed CA and to predict the clinical possibility of cytokeratin-19 soluble in serum fragment (CYFRA 21-1) as a screening tool in asymptomatic adults aged over 45 years. METHODS: Four hundred and seventy-nine patients with a histologically confirmed CA or benign colon polyp (BCP), 76 patients with only benign colorectal diseases and 223 negative controls with no CA or BCP detected on colonofibroscopy were investigated. Multiple tumor markers and biochemical markers were simultaneously checked by radioimmunoassay and enzyme immunoassay. RESULTS: The CYFRA 21-1 alone showed significant stepwise contrastive potential among the three groups (P<.001). Based on the receiver operating characteristic (ROC) analysis, Area under the curve (AUC) for CYFRA 21-1, with a value of 0.732 (95% confidence interval, 0.656-0.809, P<.001) for differentiating between negative controls and patients with advanced colon adenoma, was comparatively the highest among all analyzed factors. The sensitivity of CYFRA 21-1 was significantly higher than that of the other tumor markers in the diagnosis of CA and advanced CA, respectively (P<.001). CONCLUSIONS: Considering the results of our study, CYFRA 21-1 showed a significant diagnostic performance and significant stepwise comparative potential in differentiating patients with CA from benign controls. CYFRA 21-1 could be a simple and effective screening test for the diagnosis of CA.

Autocrine fibroblast growth factor 18 signaling mediates Wnt-dependent stimulation of CD44-positive human colorectal adenoma cells.

Expansion of a stem-like subpopulation with increased growth and survival potential is thought to drive colorectal tumor growth and progression. We investigated a CD44-positive (CD44((+))) subpopulation with extended growth and survival capacity in the human colon adenoma cell line LT97. This subpopulation expressed elevated levels of fibroblast growth factor 18 (FGF18) and fibroblast growth factor receptor FGFR3-IIIc. Expression levels of the FGFR3-IIIb, which does not bind FGF18, were similar in CD44((+)) and CD44((-)). Addition of FGF18 to the medium or its overexpression from an adenoviral vector increased the colony formation capacity of CD44((+)) threefold, and stimulated phosphorylation of ERK and GSK3ß in both total LT97 populations and CD44((+)) cells. FGFR3 signaling blockade by expression of a dominant-negative FGFR3-IIIc mutant led to inhibition of both colony formation and down-stream signaling in the CD44((+)) cells. CD44((-)) cells did not respond. Blockade of the wnt-pathway by a dominant-negative Tcf4-mutant inhibited FGFR3 activation in LT97 cells as well as in HT29 colorectal cancer cells. The chemical wnt-inhibitor sulindac sulfide amide inhibited expression of FGF18 and FGFR3-IIIc and led to inhibition of receptor activation to less than 30% of control treated cells, both in LT97 and HT29 cultures. Our results demonstrate that an FGF18/FGFR3-IIIc autocrine growth and survival loop is up-regulated in a wnt-dependent manner and drives tumor cell growth in a subpopulation of colon adenoma cells. This subpopulation can be regarded as a precursor of colon cancer development and can be targeted for CRC-prevention by blocking either wnt- or FGFR3-signaling.

Sequential expression of miR-182 and miR-503 cooperatively targets FBXW7, contributing to the malignant transformation of colon adenoma to adenocarcinoma.

Genetic changes in colon cancer are known to parallel the tissue abnormalities associated with the disease, namely adenoma and adenocarcinoma. The role of microRNA dysregulation in dysplastic progression, however, is not well understood. Here, we show that miR-182 and miR-503 undergo sequential up-regulation and drive the progression of colon adenoma to adenocarcinoma by cooperatively down-regulating the tumour suppressor FBXW7. We identified that increased expression of miR-182 is a feature of adenomas. A subsequent increase in miR-503 expression works cooperatively with miR-182 to induce transformation of an adenoma to adenocarcinoma. We show that introducing miR-503 into AAC1 cells, which are derived from a benign adenoma, confers tumourigenic potential. We also demonstrated that blocking both miR-182 and miR-503 in HCT116 colon cancer cells resulted in increased FBXW7 expression and significantly reduced tumour size in xenograft models. We confirmed relevance of these results in patients by examining the expression levels of miR-182 and miR-503 in over 200 colon cancer patients with 12 year survival outcome data. Decreased patient survival was correlated with elevated expression of both miRNAs, suggesting that elevated levels of both miR-182 and miR-503 define a novel prognostic biomarker for colon cancer patients. In conclusion, we show that a sequential expression of miR-182 and miR-503 in benign adenoma cooperatively regulates the tumour suppressor FBXW7, contributing to the malignant transformation of colon adenoma to adenocarcinoma and miR-182 and miR-503 may prove to be novel therapeutic targets. Array data are available at: http://www.oncomir.umn.edu/

Clinical characteristics of symptomatic young patients with colonic adenomas.

Background: The incidence of colonic adenomas and colorectal cancer has been on the rise among young patients. In this study, we aimed to describe the characteristics of young patients (<50 years) with adenomatous polyps and to characterize those polyps. We also aimed to determine appropriate surveillance intervals for young patients. Methods: We performed a retrospective chart review of patients <50 years of age who had polypectomy of 1 or more adenomatous polyps on colonoscopy between 2008 and 2021. Patient demographics, colonoscopy indication and polyp characteristics were obtained from the chart. Timing and findings on surveillance colonoscopies were recorded. Results: A total of 610 patients were included: mean age 42.9±5.9 years, 61% males, body mass index 27.5±4.7 kg/m2, and over 50% smokers. The most common indications were abdominal pain (23.3%), rectal bleeding (22.3%), and change in bowel habits (17.6%). Almost half of the patients who had adenomas (299) were younger than 45 years. Tubular adenoma was the most frequently encountered type of polyp (571; 93.6%). Mean polyp size was 1.1±0.9 cm. The most common location of adenomas was the sigmoid colon (41%). Of patients with adenomas, 156 (26%) had surveillance colonoscopy within 2.9±2.3 years; 74 patients (47.4%) were found to have new adenomas. Conclusions: Patients aged <50 years with colonic adenomas were mostly males, overweight, and smokers. Further adenomas were found in 47% of surveillance colonoscopies, and most were encountered within 5 years. High rates of recurrent adenomas in people <50 years of age may warrant frequent surveillance.

Use of Laxative-Augmented Contrast Medium Increases the Accuracy in the Detection of Colorectal Neoplasms.

Colonic adenomas are considered a precursor of colorectal cancer. A 75-year-old woman had a history of post-operation left breast cancer. She received an excision when the left chest wall recurred. A later FDG PET/CT scan revealed a focal intense FDG accumulation in the sigmoid, a focal mild FDG uptake in the pericolic lymph node, and a focal increased FDG accumulation in the transverse colon. A delayed FDG PET/CT scan after the per-rectal administration of the laxative-augmented contrast medium revealed a filling defect with persistent FDG uptake in the sigmoid and transverse colon and mild FDG uptake in the pericolic lymph node. In addition, more lesions were observed in the rectum and descending colon. The pathology reports showed sigmoid adenocarcinoma with lymph node metastasis, and adenomas in the transverse colon, descending colon, and rectum.

Two Cases of Increased Gastrointestinal Polyps in Familial Adenomatous Polyposis following Antiacid Agent Intake.

Introduction: Familial adenomatous polyposis (FAP), a hereditary disorder of the gastrointestinal tract, is an autosomal dominant inherited condition caused by germline mutations in the adenomatous polyposis coli (APC) gene. It is characterized by the development of hundreds to thousands of colorectal adenomatous polyps, which, if left untreated, can eventually develop into colorectal carcinomas. Representative extracolonic tumors in FAP include multiple duodenal adenomas and desmoid tumors. Moreover, multiple fundic gland polyps are frequently identified in the stomachs of patients with FAP. Case Presentation: Herein, we report the two cases. A 52-year-old woman who underwent total colectomy for FAP, and pancreatoduodenectomy was initiated on esomeprazole for the treatment of anastomotic erosion. Esophagogastroduodenoscopy performed 42 months later showed an increased number and size of gastric fundic gland polyps, which subsequently decreased after replacing esomeprazole with ranitidine. Similarly, a 39-year-old woman with FAP was initiated on vonoprazan for the treatment of reflux symptoms. Esophagogastroduodenoscopy and colonoscopy performed 14 months later indicated an increase in the number of gastric fundic gland polyps and colorectal polyps, which subsequently decreased after vonoprazan discontinuation. In these two cases, the increase and decrease in the number and size of fundic gland polyps and colon adenoma were associated with serum gastrin levels. Conclusion: Gastric fundic gland polyps and colon polyps may rapidly increase in number and size due to increased gastrin levels induced by proton pump inhibitor/potassium-competitive acid blocker use. Hence, these drugs should be prescribed with caution.

Usefulness of AI-Equipped Endoscopy for Detecting Colorectal Adenoma during Colonoscopy Screening: Confirm That Colon Neoplasm Finely Can Be Identified by AI without Overlooking Study (Confidential Study).

In the present prospective case series study, we investigated the lesion-detection ability of an AI-equipped colonoscopy as an addition to colonoscopy (CS) screening. Participants were 100 patients aged ≥20 years who had not undergone CS at the study site in the last 3 years and passed the exclusion criteria. CS procedures were conducted using conventional white light imaging and computer-aided detection (CADe). Adenoma detection rate (ADR; number of individuals with at least one adenoma detected) was compared between the conventional group and the CADe group. Of the 170 lesions identified, the ADR of the CADe group was significantly higher than the ADR of the conventional group (69% vs. 61%, p = 0.008). For the expert endoscopists, although ADR did not differ significantly, the mean number of detected adenomas per procedure (MAP) was significantly higher in the CADe group than in the conventional group (1.7 vs. 1.45, p = 0.034). For non-expert endoscopists, ADR and MAP were significantly higher in the CADe group than in the conventional group (ADR 69.5% vs. 56.6%, p = 0.016; MAP 1.66 vs. 1.11, p < 0.001). These results indicate that the CADe function in CS screening has a positive effect on adenoma detection, especially for non-experts.

Single-cell transcriptomic analysis of normal and pathological tissues from the same patient uncovers colon cancer progression.

The aim of the present study was to elucidate the evolutionary trajectory of colon cells from normal colon mucosa, to adenoma, then to carcinoma in the same microenvironment. Normal colon, adenoma and carcinoma tissues from the same patient were analyzed by single-cell sequencing, which perfectly simulated the process of time-dependent colon cancer due to the same microenvironment. A total of 22 cell types were identified. Results suggest the presence of dominant clones of same cells including C2 goblet cell, epithelial cell subtype 1 (Epi1), enterocyte cell subset 0 (Entero0), and Entero5 in carcinoma. Epi1 and Entero0 were Co-enriched in antibacterial and IL-17 signaling, Entero5 was enriched in immune response and mucin-type O-glycan biosynthesis. We discovered new colon cancer related genes including AC007952.4, NEK8, CHRM3, ANO7, B3GNT6, NEURL1, ODC1 and KCNMA1. The function of TBC1D4, LTB, C2CD4A, AND GBP4/5 in T cells needs to be clarified. We used colon samples from the same person, which provide new information for colon cancer therapy.

Epidemiology and risk of colorectal cancer in patients with a history of Helicobacter pylori infection: a population-based study.

Background: Numerous modifiable risk factors have been associated with colon cancer. Helicobacter pylori (H. pylori) is the most common bacterial infection worldwide and the strongest known risk factor for gastric cancer. We aim to assess whether the risk of colorectal cancer (CRC) is higher in patients with a history of H. pylori infection. Methods: A validated multicenter and research platform database of more than 360 hospitals was queried. Patients aged 18-65 years were included in our cohort. We excluded all patients who had previously had a diagnosis of inflammatory bowel disease or celiac disease. Univariate and multivariate regression analyses were used to calculate CRC risk. Results: A total of 47,714,750 patients were selected after application of the inclusion and exclusion criteria. The 20-year-period prevalence rate of CRC in the United States population from 1999 to September 2022 was 370 of 100,000 individuals (0.37%). According to multivariate analysis, the risk of CRC was higher in smokers (odds ratio [OR] 2.52, 95% confidence interval [CI] 2.47-2.57), obese patients (OR 2.26, 95%CI 2.22-2.30), those with irritable bowel syndrome (OR 2.02, 95%CI 1.94-2.09), or type 2 diabetes mellitus (OR 2.89, 95%CI 2.84-2.95), and patients who had a diagnosis of H. pylori infection (OR 1.89, 95%CI 1.69-2.10). Conclusion: We provide the first evidence from a large population-based study demonstrating an independent association between a history of H. pylori infection and CRC risk.

Morphological and molecular characterization of colorectal sessile serrated lesions with dysplasia.

In sessile serrated lesions (SSLs) with adenomatous dysplasia, the dysplastic component and the serrated component without dysplasia should be considered as part of the same lesion, classified as SSL with dysplasia. However, some of these lesions may actually represent collisions between a serrated polyp and a conventional adenoma. Further supporting the "collision theory", conventional adenomatous dysplasia may be found in association with hyperplastic polyps (HPs). In order to determine the molecular and biological landscape of conventional type dysplasia in serrated lesions, we collected 17 cases of colorectal serrated lesions with adenomatous dysplasia, classifying them as SSL with dysplasia (n = 10) or as mixed lesions comprising a HP component and a conventional adenomatous component (n = 7). We characterized the dysplastic and the non-dysplastic component of each lesion, after microdissection, through the targeted mutational analysis of 11 commonly altered genes in colorectal cancer (AKT1, APC, BRAF, CTNNB1, KIT, KRAS, NRAS, PDGFRA, PIK3CA, PTEN and TP53). We also characterized MMR and p53 status by immunohistochemistry. Overall, 14/17 (82.4 %) cases harbored a mutation in at least one of the two components. The most altered genes were BRAF in 10/17 (58.8 %) cases, APC in 2/17 (11.8 %) and TP53 in 4/17 (23.5 %). Among the SSL with dysplasia, the mutational profile was concordant between the two components in 7/10 (70 %) cases, while among the mixed lesions, the mutational profile was concordant in 1/7 (14.3 %). In all but two cases of SSL with dysplasia, MMR status was concordant between the two components of the serrated lesions. Our findings suggest that adenomatous dysplasia may develop in SSL as part of the serrated lesion, even if some SSL with dysplasia may actually be collision lesions. On the other hand, the polyps that are morphologically classifiable as mixed lesions composed of a HP and a conventional adenomatous component are more likely to be collision lesions.

Primary hepatic neuroendocrine carcinoma with colon adenoma: A case report with literature review.

INTRODUCTION AND IMPORTANCE: Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare, and the clinical symptoms, test results, and imaging characteristics are nonspecific in most patients; thus, it is difficult to differentiate from other liver masses before surgery. Histopathology and immunohistochemistry are the main basis for the diagnosis. PHNETs and colon tumors co-occur in a patient and are non-homologous, as reported in the English-language literature for the first time. CASE PRESENTATION: We present a case of a 60-year-old woman with right hepatic lobe mass accidentally discovered on abdominal ultrasonography during a routine examination. Preoperative liver contrast-enhanced computed tomography suggested hepatocellular carcinoma; then, surgery were performed. Pathological results revealed a Grade 2 neuroendocrine tumor of the liver. In search of the primary tumor, upper and lower endoscopy of the GI tract was performed and revealed a mass in the ascending colon. Ascending colon cancer was considered; then, laparoscopic right hemicolectomy was performed. Pathological results suggested tubular villous adenoma of the ascending colon. The final diagnosis was not colon cancer with liver metastases but was PHNETs with colon adenoma. CLINICAL DISCUSSION: PHNETs are rare cancers that are difficult to diagnose, requiring not only differentiation from other liver masses but also exclusion of metastases from extrahepatic sources. The pathological results play an important in making an accurate diagnosis. CONCLUSION: Pathology, postoperative follow-up, and comprehensive imaging examinations are powerful tools in the diagnosis of PHNETs. Currently, surgery is the best treatment to achieve a potential cure and prolong the patient's survival.

Detection of colorectal cancer using a small molecular fluorescent probe targeted against c-Met.

Colorectal cancer (CRC), a highly heterogeneous genetic disease, is currently the second leading cause of cancer-related deaths worldwide. This malignant cancer is typically preceded by the development of precancerous lesions, which are challenging to distinguish their subtle morphologic changes. Molecular-based fluorescence imaging can effectively identify lesion targets to enhance image contrast and improve the detection of early neoplasia comparing to conventional wide-light screening endoscopy. C-Met has been identified as overexpressed in CRC advanced stage and has been suggested as a validated potential theranostic target. Herein, we developed a new small molecular fluorescence probe, namely Crizotinib-PEG4-MPA, specifically binds to c-Met in CRC cells and colitis-associated cancer adenoma. In vitro binding studies confirmed the specificity and selectively of Crizotinib-PEG4-MPA against c-Met, the corresponding apparent equilibrium dissociation constants (Kd) was 3.86 µM for Crizotinib-PEG4-MPA. Additionally, the probe was carried out to c-Met positive tumor-bearing mice in vivo to explore the diagnostic potential clinical value, the method used a randomized block design to cluster mice into groups and found the tumor/normal signal ratio value up to 4.23 (95% confidence interval (CI) 4.07-4.39) at 6 h. More importantly, Crizotinib-PEG4-MPA was used to detect the occurrence of the colon adenoma and the in vivo imaging results showed the mean fluorescence intensity of the CAC colon is significantly higher than that in the normal group (P < 0.001). Furthermore, the immunofluorescence signals of biopsies samples demonstrated the probe indeed targets the c-Met and possesses the property to distinguish colon adenoma from normal colon tissue. Altogether, this novel fluorescence probe, with excellent C-met-targeting ability, has a substantial potential to serve as a widely available in vivo tracer for the early diagnosis and monitoring of colorectal cancer.