Risk Of Developing Colorectal Cancer Research Articles

Abstract 1480: Perfluorooctanesulfonic acid exposure promotes pathological changes in normal intestinal tissues which may lead to an increased risk of colorectal cancer development

Abstract Introduction: Long-term exposures to per- and polyfluoroalkyl substances (PFAS) have been increasingly linked to negative health outcomes including metabolic disorders, reduced immune responses, and increased risk of cancer. PFOS, one the most frequently detected PFAS in drinking water, is readily absorbed in the GI tract and distributes predominantly to the plasma and liver. Even though recent studies demonstrate that PFOS can cause an imbalance of cecal gut microbiota, alter microbiota diversity, and promote inflammation and gut barrier dysfunction, there is still not much known about the effects of PFOS exposure on normal and pre-malignant intestinal tissues and its contribution to carcinogenesis. Therefore, the goal of this study is to investigate the effects of PFOS on normal (I) and malignant intestinal cells (II). Methods: The effect of PFOS on gene expression profile was assessed by RNAseq analysis in intestinal tissue of C57BL/6 mice. Tumor organoids were established from Apc/VillinCre mice (adenoma models). Organoid cultures, colorectal cancer (CRC) and primary normal intestinal cell lines have been treated with 1μg/ml of PFOS. To access the mechanisms involved in PFOS-induced intestinal alterations, qRT-PCR, western blot, immunofluorescence, cytokine array and metabolomics analysis have been performed. Results: The RNAseq analysis showed that PFOS exposure is associated with transcriptome alterations with exacerbated changes in pathways involved in lipid metabolism, immune system regulation and pro-carcinogenesis signaling. PFOS exposure leads to a significant decrease in expression of 3-hydroxy-3-methylglutaryl-Coa synthase 2 (HMGCS2), a rate limiting ketogenic enzyme, in intestinal tissues. We also showed that PFOS exposure upregulates fatty acid synthase, a key enzyme of de novo lipogenesis, programmed death-ligand, an immune checkpoint inhibitor, and altered the levels of pro-inflammatory cytokines and metabolites. Using HMGCS2 knockout cells, we identified the possible contribution of HMGCS2 in cytokine regulation and activation of oncogenic pathways. Conclusion: In summary, our data suggests that PFOS may induce gastrointestinal pathological changes that can increase the risk of CRC development. Further studies are warranted to determine the functional significance of PFOS-mediated downregulation of HMGCS2 and upregulation of lipid metabolism in intestinal cells. Delineating the effects of PFOS on intestinal epithelium may contribute to development of interventional strategies to eliminate harmful effects of these environmental pollutants. Citation Format: Josiane Weber Tessmann, Jerika Durham, Ryan Goettl, Dang he, Chi Wang, Pan Deng, Bernhard Hennig, Yekaterina Zaytseva. Perfluorooctanesulfonic acid exposure promotes pathological changes in normal intestinal tissues which may lead to an increased risk of colorectal cancer development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1480.

Chemopreventive Effect of an In Vitro Digested and Fermented Plant Sterol-Enriched Wholemeal Rye Bread in Colon Cancer Cells.

Diet is crucial for the prevention of colorectal cancer. Whole grains are the source of beneficial compounds for this, such as fiber. The enrichment of wholemeal rye bread with plant sterols (PSs) could increase its beneficial effects. This study aimed to assess the potential antiproliferative effect of this enriched food on colon adenocarcinoma cells (Caco-2) compared with a non-enriched one. After a human oral chewing, simulated semi-dynamic gastrointestinal digestion and colonic fermentation in a simgi® system, fermentation liquids (FLs) obtained were used as treatment for cells. Cytotoxicity assay showed that samples diluted 1/5 (v/v) with DMEM are not toxic for non-tumoral cells, whereas they damage tumoral cells. Samples with PS (FLPS) produced a higher chemopreventive effect (vs. blank) in MTT and apoptosis assays, as well as higher gene expression of TP53 and Casp8. Nevertheless, FL0 (without PS) produced a higher chemopreventive effect in a cell cycle and reduced glutathione and calcium assays, besides producing higher gene expression of Casp3 and lower CCND1. The distinct antiproliferative effect of both FLs is attributed to differences in PSs, short chain fatty acids (lower concentration in FLPS vs. FL0) and antioxidant compounds. These results may support wholemeal rye bread consumption as a way of reducing the risk of colorectal cancer development, although further research would be needed.

Greasing the Wheels of Pharmacotherapy for Colorectal Cancer: the Role of Natural Polyphenols.

The main purpose of this review, mainly based on preclinical studies, is to summarize the pharmacological and biochemical evidence regarding natural polyphenols against colorectal cancer and highlight areas that require future research. Typically, colorectal cancer is a potentially preventable and curable cancer arising from benign precancerous polyps found in the colon's inner lining. Colorectal cancer is the third most common cancer, with a lifetime risk of approximately 4 to 5%. Genetic background and environmental factors play major roles in the pathogenesis of colorectal cancer. Theoretically, a multistep process of colorectal carcinogenesis provides enough time for anti-tumor pharmacotherapy of colorectal cancer. Chronic colonic inflammation, oxidative stress, and gut microbiota imbalance have been found to increase the risk for colorectal cancer development by creating genotoxic stress within the intestinal environment to generate genetic mutations and epigenetic modifications. Currently, numerous natural polyphenols have shown anti-tumor properties against colorectal cancer in preclinical research, especially in colorectal cancer cell lines. In this review, the current literature regarding the etiology and epidemiology of colorectal cancer is briefly outlined. We highlight the findings of natural polyphenols in colorectal cancer fromin vitro and in vivo studies. The scarcity of human trials data undermines the clinical use of natural polyphenols as anti-colorectal cancer agents, which should be undertaken in the future.

CSwinDoubleU-Net: A double U-shaped network combined with convolution and Swin Transformer for colorectal polyp segmentation

The early detection of polyps from colonoscopy can reduce the risk of colorectal cancer development and give timely treatment. Accurate polyp segmentation during colonoscopy examinations can help clinicians locate the polyps which is of great significance in the clinical prevention of colorectal cancer. However, due to large variations in terms of size, color, texture, and morphology of polyps, the similarity between the polyp lesions and their background, the variations of illumination, motion blur, low-contrast areas, intestinal contents during image acquisitions, precisely polyp segmentation is still an open issue. To overcome the challenges above, a new double U-shaped image segmentation network combining convolution structure and Shifted Windows (Swin) Transformer, namely CSwinDoubleU-Net, is proposed in this paper. The developed CSwinDoubleU-Net consists of two U-shaped encode-decode structures associated with a pure CNN-based structure and a pure Transformer-based one, and a feature fusion module that interacts with the two U-shaped parts. The first U-shaped codecs network utilizes the multi-convolution layers to extract the local feature information and the coordinate attention module in each skip connection to effectively reduce the loss of spatial information and obtain the accurate position information of the encoded features. Next, the second U-shaped codecs network uses the Swin Transformer layers with the sliding window to extract global feature information further. At last, a convolutional feature and self-attention feature fusion module (CSFFM) is designed to deeply fuse the local convolutional features extracted from the first U-shape structure and the global self-Attention features extracted from the second U-shape structure. The obtained multi-category and multi-dimensional fused feature information can help to recover the boundary features of polyps. Extensive experiments are conducted to validate the proposed CSwinDoubleU-Net on five publicly available datasets, including CVC-ClinicDB, Kvasir, CVC-ColonDB, CVC-T, and ETIS-Larib. The results show that the proposed model can outperform some state-of-the-art methods and achieve high segmentation performance for polyp images.

Beneficial effects of alpha-1 antitrypsin therapy in a mouse model of colitis-associated colon cancer

BackgroundIt is widely accepted that chronic inflammatory bowel diseases significantly higher a risk for colorectal cancer development. Among different types of treatments for patients with colon cancer, novel protein-based therapeutic strategies are considered.AIMTo explore the effect of human plasma alpha-1 antitrypsin (AAT) protein in the chemically induced mouse model of colorectal cancer.MethodsBALB/c mice with azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colitis-associated colorectal cancer (CAC), we intraperitoneally treated with commercial preparation of human plasma AAT (4 mg per mouse). Effects of this therapy were evaluated histologically, and by immunohistochemical and gene expression assays.ResultsWhen compared with non-treated controls, AOM/DSS mice receiving AAT therapy exhibited significantly longer colons, and less anal bleeding. Concurrently, AAT-treated mice had significantly fewer polyps, and lower numbers of large colon tumors. Immunohistochemical examinations of colon tissues showed significantly lower neutrophil counts, more granzyme B-positive but fewer MMP9 (gelatinase B)-positive cancer cells and lower numbers of apoptotic cells in mice receiving AAT therapy. The expression levels of IL4 were significantly higher while TNFA was slightly reduced in tumor tissues of AOM/DSS mice treated with AAT than in AOM/DSS mice.ConclusionHuman AAT is an acute phase protein with a broad-protease inhibitory and immunomodulatory activities used as a therapeutic for emphysema patients with inherited AAT deficiency. Our results are consistent with previous findings and support an idea that AAT alone and/or in combination with available anti-cancer therapies may represent a new personalized approach for patients with colitis-induced colon cancer.

Bleeding After Endoscopic Resection of Colonic Adenomatous Polyps Sized 4-10 mm.

Introduction: Colonoscopy with polypectomy is an efficacious procedure in reducing the risk of colorectal cancer development, the precursor are adenomatous polyps. The most common method for resection of polyps measuring 4-10 mm are cold (CSP) and hot snare polypectomy (HSP). CSP has a lower incidence of adverse events, especially delayed post-polypectomy bleeding. Aim: To evaluate the presence of immediate and delayed bleeding in the cold snare polypectomy of sub-centimeter polyps of the colon compared with hot snare polypectomy. Materials and Methods: This prospective clinical study is comprised all patients who were incidentally detected to have adenomatous colonic polyps measuring 4-10 mm during a colonoscopy screening. Polypectomy was done with (hot snare) or without electrocautery (cold snare). After removal of polyps, immediate bleeding, delayed bleeding, and methods for were analyzed. Results: The CSP and HSP groups included 116 patients, 113 (54.4%) polyps in 61 (52.6%) patients with CSP while 95 (45.6%) polyps in 55 (47.4%) patients with HSP. 25 (22.1%) polyps after CSP had immediate bleeding. In 5 patients (20.0%), five hemostatic clips were inserted after CSP for bleeding longer than 150 sek. The average percentage difference between immediate bleeding versus total number of resected polyps using the cold snare method is not statistically significant (p<0.05) (Difference test, p=0.0000). Delayed bleeding was not registered using this method. In the second investigated group (HSP), one patient had delayed bleeding. This was stopped with 2 clips. Immediate bleeding was not registered. Conclusion: CSP is safer than HSP in resecting colon polyps sized 4-10 mm, without risk of delayed bleeding.

Human Gut Microbiome – how intestinal bacteria influence our health

Introduction: Gut microbiome is composed of hundreds of different bacterial species.Possibly every type of bacteria can affect many different aspects of human healthGut bacterial composition varies immensely between healthy and sick people and there are many factors which can influence micriobiota balance in our intestines.&#x0D; Aim of study: The purpose of the study was to review the latest literature on the gut bacteria importance and to discover what factors can influence gut microbiome composition.&#x0D; Matherials and methods: A systemic review was conducted using Google Scholar, PubMed and ScienceDirect databases and the search was limited to studies published between 2000 and 2023. The search strategy was based on following terms: microbiome, gut bacteria, health and microbiome, gut microflora, human intestinal microbiota&#x0D; Results: We found many different studies which show importance of gut microflora in various different ailments and diseases, we have also found many showing factors that influence intestinal microbiota composition.Conclusions: Gut microbiota is very broad topic – it can affect many different aspects of human health, starting from lowering the risk of developing allergy or affecting weight loss to affecting risk of colorectal cancer development . It can be affected by many different factors – lots of them are still uknown and need further studies.

Prediagnostic serum calcium concentrations and risk of colorectal cancer development in 2 large European prospective cohorts

BackgroundHigher dietary calcium consumption is associated with lower colorectal cancer (CRC) risk. However, little data are available on the association between circulating calcium concentrations and CRC risk. ObjectivesTo explore the association between circulating calcium concentrations and CRC risk using data from 2 large European prospective cohort studies. MethodsConditional logistic regression models were used to calculate multivariable-adjusted ORs and 95% CIs in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC; n-cases = 947, n-controls = 947) and the UK Biobank (UK-BB; n-cases = 2759, n-controls = 12,021) cohorts. ResultsIn EPIC, nonalbumin-adjusted total serum calcium (a proxy of free calcium) was not associated with CRC (OR: 0.94; 95% CI: 0.85, 1.03; modeled as continuous variable, per 1 mg/dL increase), colon cancer (OR: 0.93; 95% CI: 0.82, 1.05) or rectal cancer (OR: 1.01; 95% CI: 0.84, 1.20) risk in the multivariable adjusted model. In the UK-BB, serum ionized calcium (free calcium, most active form) was inversely associated with the risk of CRC (OR: 0.85; 95% CI: 0.76, 0.95; per 1 mg/dL) and colon cancer (OR: 0.78; 95% CI: 0.68, 0.90), but not rectal cancer (OR: 1.02; 95% CI: 0.83, 1.24) in multivariable adjusted models. Meta-analysis of EPIC and UK-BB CRC risk estimates showed an inverse risk association for CRC in the multivariable adjusted model (OR: 0.90; 95%CI: 0.84, 0.97). In analyses by quintiles, in both cohorts, higher levels of serum calcium were associated with reduced CRC risk (EPIC: ORQ5vs.Q1: 0.69; 95% CI: 0.47, 1.00; P-trend = 0.03; UK-BB: ORQ5vs.Q1: 0.82; 95% CI: 0.72, 0.94; P-trend < 0.01). Analyses by anatomical subsite showed an inverse cancer risk association in the colon (EPIC: ORQ5vs.Q1: 0.63, 95% CI: 0.39, 1.02; P-trend = 0.05; UK-BB: ORQ5vs.Q1: 0.75; 95% CI: 0.64, 0.88; P-trend < 0.01) but not the rectum. ConclusionsIn UK-BB, higher serum ionized calcium levels were inversely associated with CRC, but the risk was restricted to the colon. Total serum calcium showed a null association in EPIC. Additional prospective studies in other populations are needed to better investigate these associations.

Genome-Wide Association Study of Metachronous Colorectal Adenoma Risk among Participants in the Selenium Trial

Genetic variants related to colorectal adenoma may help identify those who are at highest risk of colorectal cancer development or illuminate potential chemopreventive strategies. The purpose of this genome-wide association study was to identify genetic variants that are associated with risk of developing a metachronous colorectal adenoma among 1,215 study participants of European descent from the Selenium Trial. Associations of variants were assessed with logistic regression analyses and validated in an independent case-control study population of 1,491 participants from the Colorectal Cancer Study of Austria (CORSA). No statistically significant genome-wide associations between any variant and metachronous adenoma were identified after correction for multiple comparisons. However, an intron variant of FAT3 gene, rs61901554, showed a suggestive association (P = 1.10 × 10−6) and was associated with advanced adenomas in CORSA (P = 0.04). Two intronic variants, rs12728998 and rs6699944 in NLRP3 were also observed to have suggestive associations with metachronous lesions (P = 2.00 × 10−6) in the Selenium Trial and were associated with advanced adenoma in CORSA (P = 0.03). Our results provide new areas of investigation for the genetic basis of the development of metachronous colorectal adenoma and support a role for FAT3 involvement in the Wnt/β-catenin pathway leading to colorectal neoplasia. Trial Registration number: NCT00078897 (ClinicalTrials.gov).

The potential chemo-preventive roles of Malus domestica against the risk of colorectal cancer: A suggestive insight into clinical application

Biologically active compounds in fruit-derived ingredients, particularly phytochemicals, have significant potential to modulate and mitigate many pathological processes in the development of disease conditions, including cancer. Colorectal cancer (CRC) remains a major public health issue. Nonetheless, prevention is an important step in lowering the rate of mortality from this cancer. Currently, the link between apple consumption and improved health is becoming remarkably evident and is reported to be beneficial for human health. Phytochemicals, such as flavonoids and other polyphenol compounds extensively available in apple fruits, have well-known positive effects on health outcomes and the potential to combat and prevent the development of CRC, including antioxidant, anti-proliferative, and anti-carcinogenic effects. This review describes the bioactive compounds derived from apple fruits, particularly the polyphenols and flavonoids, their proposed mechanisms responsible for their bioactive properties and health-promoting attributes that could provide potential chemo-preventive effects against the risk of CRC development. The conclusion of the review provides insights into the potential effects of apple-derived bioactive compounds and proposes the need for more clinical studies in large trials for future strategies regarding the valuable effects of apple phytochemicals, which might be therapeutic candidates in the campaign against CRC.

Impact of AKT1 polymorphism on DNA damage, BTG2 expression, and risk of colorectal cancer development.

BackgroundAKT, also called protein kinase B, is a serine-threonine kinase that functions as a mediator of PI3K-Akt-mTOR signaling pathway and plays an important role in an array of cellular processes. Many single nucleotide polymorphisms (SNP) in AKT gene have been observed to be associated with various types of cancers. In the current research the association of a functional SNP rs1130233 in AKT, depicting G to A transition, was studied with AKT activation, DNA damage, an early response B-cell translocation gene 2 (Btg2) expression and risk of colorectal cancer (CRC) development.Patients and methodsA total 197 population-based controls and 200 CRC patients were genotyped for SNP rs1130233. AKT expression, activation and BTG2 expression were determined in GG, AG and AA genotype carriers. DNA damage was determined through comet assay.ResultsThe heterozygous AG genotype (55.67%) was more prevalent in the local population compared to homozygous wild type GG (37.78%) and homozygous AA genotypes (6.55%). Moreover, AG and AA alleles were observed to be significant contributors (P = 0.01, OR = 1.80, CI = 1.18 to 2.74, and P = 0.001, OR = 5.00, CI = 1.90 to 13.18, respectively) in increasing the risk of CRC. The immunoblot analysis revealed that G to A transition decreased the expression and activation of AKT. Moreover, AG and AA genotypes of AKT1 rs1130233 showed a significant increase in DNA damage and Btg2 expression.ConclusionsThe data concludes that G to A substitution is a risk factor for CRC development involving a decrease in AKT expression and activation and increase in DNA damage.

Colorectal microbiota after removal of colorectal cancer.

The colonic microbiome has been implicated in the pathogenesis of colorectal cancer (CRC) and intestinal microbiome alterations are not confined to the tumour. Since data on whether the microbiome normalises or remains altered after resection of CRC are conflicting, we studied the colonic microbiota of patients after resection of CRC. We profiled the microbiota using 16S rRNA gene amplicon sequencing in colonic biopsies from patients after resection of CRC (n = 63) in comparison with controls (n = 52), subjects with newly diagnosed CRC (n = 93) and polyps (i = 28). The colonic microbiota after surgical resection remained significantly different from that of controls in 65% of patients. Genus-level profiling and beta-diversity confirmed two distinct groups of patients after resection of CRC: one with an abnormal microbiota similar to that of patients with newly diagnosed CRC and another similar to non-CRC controls. Consumption levels of several dietary ingredients and cardiovascular drugs co-varied with differences in microbiota composition suggesting lifestyle factors may modulate differential microbiome trajectories after surgical resection. This study supports investigation of the colonic microbiota as a marker of risk for development of CRC.

Association of GSTM1 and GSTT1 genes insertion/deletion polymorphism with colorectal cancer risk: A case-control study of Khyber Pakhtunkhwa population, Pakistan.

To evaluate the genetic association of glutathione S transferase M1 and glutathione S transferase T1 genes insertion/deletion polymorphism with the risk of colorectal cancer. This case-control study was conducted March 2018 and November 2019 at the University of Peshawar, Peshawar, Pakistan, and comprised blood samples from colorectal cancer patients and age- and gender-matched controls. Deoxyribonucleic acid was extracted from blood samples, and glutathione S transferase M1 and glutathione S transferase T1 genotyping was performed using polymerase chain reaction at the Institute of Radiation and Nuclear Medicine, Peshawar. Data regarding age, gender, location, smoking status, cancer stage and node involvement was collected on a predesigned proforma. Data was analysed using Minitab 17. The frequency of glutathione S transferase M1 was was significantly associated with colorectal cancer risk (p<0.01), while glutathione S transferase T1 null genotype showed non-significant association (p<0.43). The association between the combined deletion of glutathione S transferase M1 and glutathione S transferase T1 polymorphism and the colorectal risk was significant (p=0.011). Glutathione S transferase M1 and glutathione S transferase T1 deletions had non-significant association with age, smoking status, dwelling and tumour location (p>0.05) when compared with the wild genotypes in colorectal cancer cases. Glutathione S transferase M1 gene deletion was found to be associated with the risk of colorectal cancer development.

"B Vitamin Intake and the Risk of Colorectal Cancer Development: A Systematic Review and Meta-Analysis of Observational Studies"

"B Vitamin Intake and the Risk of Colorectal Cancer Development: A Systematic Review and Meta-Analysis of Observational Studies"

Expression of Oncogenic Molecules in Pediatric Ulcerative Colitis

Introduction: Long-term disease duration of ulcerative colitis (UC) is known to increase the risk of developing colorectal cancer in adults; however, this association has not been genetically analyzed in children with UC. Herein, we examined the expression of cancer-related genes in the colonic mucosa of pediatric UC patients and their risk of developing colorectal cancer. Methods: Microarray analysis of cancer-related gene expression was conducted on rectal mucosa biopsy specimens randomly selected from pediatric cases, including 4 active-phase UC cases, 3 remission-phase UC cases, and 3 irritable bowel syndrome control cases. The subject pool was then expanded to 10 active-phase cases, 10 remission-phase cases, and 10 controls, which were analyzed by real-time polymerase chain reaction (PCR) and immunohistochemical staining. Results: The microarray results indicated significantly higher expression levels of cancer-related genes PIM2 and SPI1 in the active group than in the remission and control groups (p < 0.05). Real-time PCR confirmed that PIM2 and SPI1 expression levels were significantly higher, whereas TP53 and APC expression levels were significantly lower, in the active-phase group than in the remission and control groups (p < 0.05). Immunohistochemical staining for PIM2, SPI1, TP53, and APC proteins supported the real-time PCR results. Conclusions: Expression levels of previously unreported cancer-related genes in adult UC patients were significantly higher in pediatric UC patients than in controls. Inflammation of the gastrointestinal mucosa increased the expression levels of cancer-related genes even in childhood-onset UC cases, suggesting that chronic inflammation from childhood may increase the risk of colorectal cancer development.

Long-term Risk of Colorectal Cancer Development According to Adenoma Detection Rate

Long-term Risk of Colorectal Cancer Development According to Adenoma Detection Rate

Inhibitory Effect of Garcinol on Obesity-Exacerbated, Colitis-Mediated Colon Carcinogenesis.

Epidemiological studies show a consistent and compelling association between the risk of colorectal cancer development and obesity, but its mechanisms remain poorly understood. Evidence is mounting that colorectal cancer can be prevented by nutritional supplements, such as phytochemicals. Garcinol, a polyisoprenylated benzophenone derivative, is widely present in Garcinia plants. This study investigates the potential role of garcinol supplementation in ameliorating obesity-induced colon cancer development. An animal model to investigate the effect of high-fat-diet (HFD)-induced obesity on promoting colitis-associated colon cancer (AOM (azoxymethane)/DSS (dextran sodium sulfate)-induced) is designed. The results show that HFD can promote colitis-associated colon cancer as compared to an AOM/DSS group without the intervention of obesity, and supplementing with 0.05% garcinol in the diet can significantly ameliorate obesity-promoted colon carcinogenesis. The results also reveals that the microbiota composition of each group is significantly different and clustered. The most representative genera are Alistipes, Romboutsia, and Ruminococcus. The RNA-sequencing results show that the administration of garcinol can regulate genes and improve obesity-promoting colitis-associated colon carcinogenesis. The study results suggest that garcinol can prevent obesity-promoted colorectal cancer, and these findings provide important niches for the future development of garcinol as functional foods or adjuvant therapeutic agents.

Evaluating the Improvement in Colonoscopy Quality Indicators Subsequent to Publication of Professional Society Guidelines.

Introduction Quality metrics of colonoscopy should be routinely monitored with a focus on optimizing the patient’s subsequent risk of colorectal cancer development. Documentation of bowel preparation, adenoma detection rate (ADR), and post-colonoscopy follow-up recommendations are three of the most important quality indicators for colonoscopy, but significant improvement has been challenging to achieve. The goal of this study is to determine whether the publication of colonoscopy quality indicator guidelines in 2015 resulted in an improvement in quality measures of physicians in our endoscopy suite as compared to before.Methods We reviewed the electronic medical records of patients who underwent a screening or surveillance colonoscopy in 2014 and 2017. Colonoscopies were performed in an open-access medical center endoscopy suite, staffed by three groups of physicians (academic gastroenterologists (AGs), non-academic gastroenterologists (non-AGs), and surgeons). We gathered demographic data, bowel preparation reports, follow-up recommendations, and notice to patient’s primary care physician, and calculated ADR for patients. Age- and gender-matched patients in both years were analyzed for ADR. These data were further subcategorized for each group of physicians.Results There were 553 patients in 2014 and 1,095 in 2017. Overall, male gender and African American race constituted the majority of patients in both years. Among age- and gender-matched patients in 2014 and 2017 (412 and 243 patients, respectively), ADR within each group of endoscopists was not significantly different between these two years (AGs 44% vs. 50%; non-AGs 32% vs. 27%; surgeons 25% vs. 21%; p>0.05 for all). However, in 2014 and 2017, ADR was significantly higher in the AG group as compared to the non-AG group and surgeons (p<0.006 and p<0.0004, respectively). Reporting of bowel preparation quality (82% vs. 87%) and documenting the recommended period for follow-up surveillance colonoscopy in the report (68% vs. 78%) improved between 2014 and 2017 (p=0.002 and p=0.0001, respectively). Correct recommendations for follow-up surveillance colonoscopy only improved significantly in the AG group (74% in 2014 as compared with 82% in 2017, p=0.003).Conclusion Based on the current guidelines, AG physicians are far exceeding the target ADR goals, and are superior compared to other groups of endoscopists. Although improvements were noted after guideline publications, areas of needed improvement with respect to meeting gastroenterology society guidelines for quality remained. The fact that individual physicians are performing and billing in an endoscopy suite staffed and equipped by a medical center creates an environment where responsibility for improvement in quality cannot be readily assigned.

Association Between rs1859168/HOTTIP Expression Level and Colorectal Cancer and Adenomatous Polyposis Risk in Egyptians.

LncRNA HOTTIP is a new lncRNA that is strictly linked to the susceptibility, growth, propagation, and prognosis of several human cancers together with colorectal cancer. lncRNA HOTTIP rs1859168 may confer colorectal cancer susceptibility through regulating its gene expression level. To elucidate its role in colorectal cancer risk, we genotyped rs1859168 A>C and measured serum HOTTIP expression level in colorectal cancer, adenomatous polyposis patients and controls by real-time polymerase chain reaction. The results displayed that rs1859168 A>C single-nucleotide polymorphism is a risk factor for colorectal cancer among adenomatous polyposis patients and controls, AC versus CC genotypes [adjusted odds ratio (OR) = 2.256, 95% confidence interval (CI) = 1.316-3.868, P = 0.003] when compared with controls and (adjusted OR = 9.521, 95% CI = 3.330-27.217, P < 0.0001) when compared with adenomatous polyposis. Serum HOTTIP was upregulated in the colorectal cancer group when compared with adenomatous polyposis or controls [median (interquartile range) = 3.64 (2.46-5.02) (P < 0.0001)]. A significant difference in serum HOTTIP was found to be associated with different rs1859168 genotypes. rs1859168 A>C and higher serum HOTTIP were significantly associated with distant metastasis, lymph nodes metastasis, and grade III of colorectal cancer. Both rs8159168 and high HOTTIP confer increased risk for colorectal cancer development. [Figure: see text].

The Role of the Gut Microbiome in Colorectal Cancer Development and Therapy Response

Colorectal cancer (CRC) is the third most common cancer worldwide and the leading cause of cancer-related deaths. Recently, several studies have demonstrated that gut microbiota can alter CRC susceptibility and progression by modulating mechanisms such as inflammation and DNA damage, and by producing metabolites involved in tumor progression or suppression. Dysbiosis of gut microbiota has been observed in patients with CRC, with a decrease in commensal bacterial species (butyrate-producing bacteria) and an enrichment of detrimental bacterial populations (pro-inflammatory opportunistic pathogens). CRC is characterized by altered production of bacterial metabolites directly involved in cancer metabolism including short-chain fatty acids and polyamines. Emerging evidence suggests that diet has an important impact on the risk of CRC development. The intake of high-fiber diets and the supplementation of diet with polyunsaturated fatty acids, polyphenols and probiotics, which are known to regulate gut microbiota, could be not only a potential mechanism for the reduction of CRC risk in a primary prevention setting, but may also be important to enhance the response to cancer therapy when used as adjuvant to conventional treatment for CRC. Therefore, a personalized modulation of the pattern of gut microbiome by diet may be a promising approach to prevent the development and progression of CRC and to improve the efficacy of antitumoral therapy.