High risk features in colorectal adenomatous polyps: A multi-institutional study.

High risk features in colorectal adenomatous polyps include size >1 cm and advanced histology: high-grade dysplasia and villous architecture. We investigated whether the diagnostic rates of advanced histology in colorectal adenomatous polyps were similar among institutions across the United States, and if not, could differences be explained by patient age, polyp size, and/or CRC rate. Nine academic institutions contributed data from three pathologists who had signed out at least 100 colorectal adenomatous polyps each from 2018 to 2019 taken from patients undergoing screening colonoscopy. For each case, we recorded patient age and sex, polyp size and location, concurrent CRC, and presence or absence of HGD and villous features. A total of 2700 polyps from 1886 patients (mean age: 61 years) were collected. One hundred twenty-four (5 %) of the 2700 polyps had advanced histology, including 35 (1 %) with HGD and 101 (4 %) with villous features. The diagnostic rate of advanced histology varied by institution from 1.7 % to 9.3 % (median: 4.3 %, standard deviation [SD]: 2.5 %). The rate of HGD ranged from 0 % to 3.3 % (median: 1 %, SD: 1.2 %), while the rate of villous architecture varied from 1 % to 8 % (median: 3.7 %, SD: 2.5 %). In a multivariate analysis, the factor most strongly associated with advanced histology was polyp size >1 cm with an odds ratio (OR) of 31.82 (95 % confidence interval [CI]: 20.52-50.25, p < 0.05). Inter-institutional differences in the rate of polyps >1 cm likely explain some of the diagnostic variance, but pathologic subjectivity may be another contributing factor.

Automated classification pipeline for real-time in vivo examination of colorectal tissue using Raman spectroscopy.

Colorectal cancer is the third most common malignancy worldwide and one of the leading causes of death in oncological patients with its diagnosis typically involving confirmation by tissue biopsy. In vivo Raman spectroscopy, an experimental diagnostic method less invasive than a biopsy, has shown great potential to discriminate between normal and cancerous tissue. However, the complex and often manual processing of Raman spectra along with the absence of a suitable instant classifier are the main obstacles to its adoption in clinical practice. This study aims to address these issues by developing a real-time automated classification pipeline coupled with a user-friendly application tailored for non-spectroscopists. First, in addition to routine colonoscopy, 377 subjects underwent in vivo acquisitions of Raman spectra of healthy tissue, adenomatous polyps, or cancerous tissue, which were conducted using a custom-made microprobe. The spectra were then loaded into the pipeline and pre-processed in several steps, including standard normal variate transformation and finite impulse response filtration. The quality of the pre-processed spectral data was checked based on their signal-to-noise ratio before the suitable spectra were decomposed and classified using a combination of principal component analysis and a support vector machine, respectively. After five-fold cross-validation, the developed classifier exhibited 100% sensitivity toward adenocarcinoma and adenomatous polyps. The overall accuracy was 96.9% and 79.2% for adenocarcinoma and adenomatous polyps respectively. In addition, an application with a graphical user interface was developed to facilitate the use of our data pipeline by medical professionals in a clinical environment. Overall, the combination of supervised and unsupervised machine learning with algorithmic pre-processing of in vivo Raman spectra appears to be a viable way of reducing the relatively large number of biopsies currently needed to definitively diagnose colorectal cancer.

Frequency of colorectal surveillance colonoscopies for adenomatous polyps: systematic review and meta-analysis.

BACKGROUND AND AIM: The purpose of this study was to assess evidence on the frequency of polyp surveillance colonoscopies performed earlier than the recommended follow-up intervals in clinical practice guidelines. METHODS: A systematic review was performed based on electronic searches in PubMed and Embase. Research articles, letters to the editors, and review articles, published before April 2022, were included. Studies that focused on the intervals of polyp surveillance in adult populations were selected. The Risk Of Bias In Non-randomized Studies of Exposure (ROBINS-E) was used to assess the risk of bias. A meta-analysis was performed with Forest plots to illustrate the results. RESULTS: In total, 16 studies, comprising 11 172 patients from Australia, Europe, and North America, were included for analysis. The quality of the studies was moderate. Overall, 38% (95% CI: 30-47%) of colonoscopies were undertaken earlier than their respective national clinical guidelines. In risk-stratified surveillance, 10 studies contained data relating to low-risk polyp surveillance intervals and 30% (95% CI: 29-31%) of colonoscopies were performed earlier than recommended. Eight studies contained data relating to intermediate-risk polyp surveillance and 15% (95% CI: 14-17%) of colonoscopies were performed earlier than recommended. One study showed that 6% (95% CI: 4-10%) of colonoscopies performed for high-risk polyp surveillance were performed earlier than recommended. CONCLUSIONS: A significant proportion of polyp surveillance was performed earlier than the guidelines suggested. This provides evidence of the potential overuse of healthcare resources and the opportunity to improve hospital efficiency.

Endoscopic differential diagnosis between foveolar-type gastric adenoma and gastric hyperplastic polyps in Helicobacter pylori-naïve patients.

BACKGROUND: Foveolar-type gastric adenoma (FGA) occurs in Helicobacter pylori (Hp)-naïve individuals and morphologically mimics Hp-naïve gastric hyperplastic polyp (HpN-GHP). FGA is often difficult to distinguish from HpN-GHP even by biopsy, due to its low-grade histologic atypia. We conducted a retrospective study to create an endoscopic diagnostic index. METHODS: We analyzed 51 FGAs in 41 patients and 36 HpN-GHPs in 24 patients. All lesions were photographed by white-light endoscopy (WLE) and narrow-band imaging with magnification endoscopy (NBIME). Three experts and three non-experts reviewed the WLE and WLE+NBIME images to assess six items for lesion diagnosis. We analyzed correlations between the diagnostic items and histologic features and compared the diagnostic accuracy between modalities. We created a composite diagnostic index and calculated its accuracy and consistency. RESULTS: FGAs more frequently showed the following features vs. HpN-GHPs: bright-red color (94.1% vs. 44.4%), peripheral hyperplasia (58.8% vs. 8.3%), papillary/gyrus-like microstructure (96.1% vs. 33.3%), visible capillaries (70.6% vs. 38.9%), and demarcation line (98.0% vs. 41.7%) (P < 0.05). White-zone thickening was seen only in HpN-GHPs (52.8%). Diagnostic accuracy (mean, WLE vs. WLE+NBIME) was 90.8 ± 1.1% vs. 93.5 ± 2.4% (P = 0.15) for experts and 88.5 ± 3.0% vs. 86.6 ± 3.5% (P = 0.51) for non-experts. When satisfying the four criteria (bright-red color, papillary/gyrus-like microstructure, demarcation line, and absent white-zone thickening), sensitivity and specificity for FGA were 90.2% and 94.4%, respectively, with a kappa value of ≥ 0.6 for interobserver diagnostic agreement. CONCLUSIONS: Composite diagnostic index contributes to the reproducible, accurate, preoperative differential diagnosis of FGA and HpN-GHP.

Diagnostic Value of Inflammation-Related Indicators in Distinguishing Early Colon Cancer and Adenomatous Polyps.

BACKGROUND: There are few clinical symptoms in early colorectal cancer, so it is necessary to find a simple and economical tumor detection index for auxiliary diagnosis. This study aims to explore the diagnostic value of preoperative inflammation-related indicators, such as neutrophil, lymphocyte, platelet count, platelet to lymphocyte ratio (PLA), neutrophil to lymphocyte ratio (NLR), and systemic immune-inflammation index (SII), for early colorectal cancer, and determine whether inflammation-related indicators can provide more accurate diagnostic judgment for patients. METHODS: This study was a retrospective study. Patients who were first diagnosed with colorectal cancer or colorectal adenomatous polyp at Beijing Friendship Hospital from October 2016 to October 2017 were retrospectively collected. According to inclusion and exclusion criteria, a total of 342 patients were included, including 216 patients with colorectal cancer and 126 patients with colorectal adenomatous polyp. Fasting venous blood and other clinical features were collected to compare the differences between colorectal cancer and colorectal adenoma. RESULTS: There were statistically significant differences in age, carcinoembryonic antigen, albumin, hemoglobin, mean platelet volume, lymphocyte, monocyte, NLR, PLA, SII, and mean platelet volume to platelet count ratio between colorectal cancer group and colorectal adenoma group (P < .05), and a Nomogram model was established. Using inflammatory markers to differentiate colorectal and colorectal polyps produced greater AUC than using tumor markers alone (.846 vs .695). CONCLUSION: Inflammation-related indicators, such as lymphocyte, monocyte, and mean platelet volume, may serve as potential indicators to assist in the diagnosis of early colorectal cancer.

In vivo Raman spectroscopy in the diagnostics of colon cancer.

Early detection and accurate diagnosis of colorectal carcinoma are crucial for successful treatment, yet current methods can be invasive and even inaccurate in some cases. In this work, we present a novel approach for in vivo tissue diagnostics of colorectal carcinoma using Raman spectroscopy. This almost non-invasive technique allows for fast and accurate detection of colorectal carcinoma and its precursors, adenomatous polyps, enabling timely intervention and improved patient outcomes. Using several methods of supervised machine learning, we were able to achieve over 91% accuracy in distinguishing colorectal lesions from healthy epithelial tissue and more than 90% classification accuracy for premalignant adenomatous polyps. Moreover, our models enabled the discrimination of cancerous and precancerous lesions with a mean accuracy of almost 92%. Such results demonstrate the potential of in vivo Raman spectroscopy to become a valuable tool in the fight against colon cancer.

Evaluation of non-gastric upper gastrointestinal system polyps: an epidemiological assessment.

Non-gastric upper gastrointestinal system polyps are detected rarely and mostly incidentally during upper gastrointestinal endoscopy. While the majority of lesions are asymptomatic and benign, some lesions have the potential to become malignant, and may be associated with other malignancies. Between May 2010 and June 2022, a total of 127,493 patients who underwent upper gastrointestinal endoscopy were retrospectively screened. Among these patients, those who had polyps in the esophagus and duodenum and biopsied were included in the study. A total of 248 patients with non-gastric polyps were included in this study. The esophageal polyp detection rate was 80.00/100,000, while the duodenal polyp detection rate was 114.52/100,000. In 102 patients (41.1%) with esophageal polyps, the mean age was 50.6 ± 15.1, and 44.1% (n = 45) were male. The most common type of polyps was squamous papilloma (n = 61, 59.8%), followed by inflammatory papilloma (n = 18, 17.6%). In 146 patients (58.9%) with duodenal polyps, the mean age of patients was 58.3 ± 16.5, and 69.8% (n = 102) were male. Brunner's gland hyperplasia, inflammatory polyp, ectopic gastric mucosa, and adenomatous polyp were reported to be the most prevalent types of polyps in the duodenum overall (28.1%, 27.4%, 14.4%, and 13.7%, respectively). It is crucial to identify rare non-gastric polyps and create an effective follow-up and treatment plan in the era of frequently performed upper gastrointestinal endoscopies. The epidemiological assessment of non-gastric polyps, as well as a follow-up and treatment strategy, are presented in this study.

Elevated Adenomatous Polyp Detection Rate Among Alaska Native and American Indian People in Interior Alaska, 2018-2022.

OBJECTIVES: Colorectal cancer (CRC) incidence and mortality are twice as high among Alaska Native people as among non-Hispanic White people in the United States; as such, colonoscopy is a recommended screening test for Alaska Native people. Adenoma detection rate (ADR) is measured in patients at average risk of CRC undergoing initial screening colonoscopy and reflects the prevalence of precancerous polyps in a screened population. We evaluated the ADR among Alaska Native people living in Interior Alaska. METHODS: This project evaluated the ADR among Alaska Native and American Indian adults aged ≥40 years (N = 460) living in Interior Alaska, using a retrospective medical record review of patients referred for screening colonoscopy from February 1, 2018, through March 31, 2022. The main outcome measure was ADR, stratified by age and sex. RESULTS: The ADR was 45.0% overall: 43.0% among women and 47.1% among men. Among patients aged ≥50 years, the ADR was 67.1%: 62.7% among women and 70.7% among men. Among patients aged 40-49 years, the ADR was 34.4%: 35.3% among women and 33.3% among men. CONCLUSIONS: Measured ADR was high among Alaska Native men and women aged ≥50 years in Interior Alaska and in all age groups that were screened. These findings have implications for which CRC screening methods, intervals, and age to begin screening are most appropriate for Alaska Native people, as well as the need for future research on the pathology, etiology, and natural history of CRC in this population.

Older Age at First Screening Colonoscopy is Associated With an Increased Risk of Colorectal Adenomas and Cancer.

INTRODUCTION: The goal of colorectal cancer (CRC) screening is to detect precancerous polyps before cancer development or identification of cancer at an early stage. Guidelines have recommended screening colonoscopy to start at age 45. Our aim was to determine the impact of delays in performing the first screening colonoscopy on the risk of adenoma or CRC detection. METHODS: We analyzed colonoscopy and histopathology data of average CRC risk patients who had their first screening colonoscopy between 2010 and 2017. Univariate and multivariable logistic regression was performed to determine the association between demographic variables and the risk of adenomas or CRC. RESULTS: A total of 1155 average risk patients underwent their initial screening colonoscopy during the study period. Median age was 54 years (range of 45-87) and 58.2% were females. In multivariable analysis, older age at first screening colonoscopy was significantly associated with the detection of adenomatous polyps (odds ratio 1.05, 95% confidence interval 1.04-1.07, P <0.001) and CRC (odds ratio 1.11, 95% confidence interval 1.06-1.16, P <0.001). The association between age and risk of adenomatous polyps (F-test 35.43, P =0.0019) and CRC (F-test 36.94, P =0.0017) fit an exponential growth model. It was estimated that the detection rate doubled every 14.20 years and 4.75 years for adenomas and CRC, respectively. CONCLUSION: We found that older age at the initial performance of a screening colonoscopy was associated with increased detection of adenomatous polyps and CRC. This work highlights the need for guideline adherence for the prevention of CRC development.

Artificial Intelligence-Aided Colonoscopy Does Not Increase Adenoma Detection Rate in Routine Clinical Practice.

The performance of artificial intelligence-aided colonoscopy (AIAC) in a real-world setting has not been described. We compared adenoma and polyp detection rates (ADR/PDR) in a 6-month period before (pre-AIAC) and after introduction of AIAC (GI Genius, Medtronic) in all endoscopy suites in our large-volume center. The ADR and PDR in the AIAC group was lower compared with those in the pre-AIAC group (30.3% vs 35.2%, P < 0.001; 36.5% vs 40.9%, P = 0.004, respectively); procedure time was significantly shorter in the AIAC group. In summary, introduction of AIAC did not result in performance improvement in our large-center cohort, raising important questions on AI-human interactions in medicine.

Familial and hereditary gastric cancer, an overview.

There are three major hereditable syndromes that affect primarily the stomach: hereditary diffuse gastric cancer (HDGC), gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) and familial intestinal gastric cancer (FIGC). HDGC is caused by germline mutations in CDH1 gene that occur in 10-40% of HDGC families and, in a minority of cases, by mutations in CTNNA1 gene. GAPPS is caused by germline mutations in the promoter 1B of APC gene, and the genetic cause of FIGC is not fully elucidated. Gastric cancer can also be observed as part of other inherited cancer disorders, namely in familial adenomatous polyposis, MUTYH-associated polyposis, Peutz-Jeghers syndrome, juvenile polyposis syndrome, Lynch syndrome, Li-Fraumeni syndrome, Cowden syndrome, and hereditary breast and ovarian cancer syndrome. In this article, the state of the art of familial gastric cancer regarding the clinical, molecular and pathology features is reviewed, as well as the practical aspects for a correct diagnosis and clinical management.

BidSi6 and BidEL isoforms as a potential marker for predicting colorectal adenomatous polyps.

BACKGROUND: As a well-known protein, Bid links the extrinsic and intrinsic apoptotic pathways and plays important roles in cell proliferation. In this study, we evaluated the expression of two isoforms of the Bid gene (BidSi6 and BidEL) in colorectal adenomatous polyps as a biomarker and investigated the relationship between their expression levels with clinicopathological factors. METHODS: The expression of BidSi6 and BidEL isoforms in 22 pairs of Adenomatous polyps and adjust non-polyp tissues was measured by qReal-Time PCR and compared with 10 normal colon tissues. ROC curve was performed to examine the diagnostic capacity. Also, sequencing was performed for molecular identification of BidSi6 isoform in adenomatous polyp. RESULTS: Our results showed that BidSi6 and BidEL isoforms were significantly overexpressed in Adenomatous polyps and non-polyp adjacent tissues from the same patients compared to that in normal colon tissues, but there was no significant expression between polyps and adjust non-polyp tissues. There were no significant correlations between the expression of two isoforms and other features of clinicopathology. The area under the curve of BidSi6 and BidEL isoforms indicated powerful diagnostic capability. The phylogenetic tree was constructed based on the sequence of idSi6 isoform, and the results showed that adenomatous polyp tissue and adjust non-polyp tissue were separated from healthy colorectal tissue and reference sequence (EU678292). CONCLUSIONS: These findings suggest that BidSi6 and BidEL isoforms can be used as new potential biomarkers in adenomatous polyps.

A New Risk-Scoring System for Colorectal Cancer and Polyp Screening by Turkish Colorectal Cancer and Polyp Study Group.

BACKGROUND: Colorectal cancer is one of the most commonly diagnosed types of cancer worldwide. An early diagnosis and detection of colon cancer and polyp can reduce mortality and morbidity from colorectal cancer. Even though there are a variety of options in screen- ing tests, the question remains on which test is the most effective for the early detection of colorectal cancer. In this prospective study, we aimed to develop a simple, useful, effective, and reliable scoring system to detect colon polyp and colorectal cancer. METHODS: We enrolled 6508 subjects over the age of 18 from 16 centers, with colonoscopy screening. The age, smoking status, alcohol consumption, body mass index, polyp incidence, polyp size, number and localization, and pathologic findings were recorded. RESULTS: The age, male gender, obesity, smoking, and family history were found as independent risk factors for adenomatous polyp. We have developed a new scoring system which can be used for these factors. With a score of 4 or above, we found the following: sensitivity 81%, specificity 40%, positive predictive value 25.68%, and negative predictive value 89.84%, for adenomatous polyp detection; and sensitivity 96%, specificity 39%, positive predictive value 3.35%, negative predictive value 99.29%, for colorectal cancer detection. CONCLUSION: Even though the first colorectal cancer screening worldwide is generally performed for individuals over 50 years of age, we recommend that screening for colorectal cancer might begin for those under 50 years of age as well. Individuals with a score ≥ 4 must be included in the screening tests for colorectal cancer.

Prevalence of Adenomas on Surveillance Colonoscopies for Patients with a History of Colonic Polyps of Unknown Histology.

BACKGROUND: Guidelines for surveillance colonoscopy depend on polyp histology. When patients present to a new healthcare system and report a personal history of "colon polyps," however, information on polyp histology is frequently unavailable. AIMS: To assess adenoma prevalence in patients with a history of colonic polyps of unknown histology and to compare it to patients undergoing either screening colonoscopy or surveillance colonoscopy for known adenomatous polyps. METHODS: This cohort study evaluated colonoscopies of patients ≥ 50 years of age over a 14-year period at a single institution. The exposure of interest was colonoscopy indication, categorized into three groups: screening colonoscopy, surveillance colonoscopy for history of colonic polyp(s) of unknown histology, and surveillance colonoscopy for history of adenoma(s). The primary outcome was adenoma detection rate. Multivariable logistic regression was used to assess the association between colonoscopy indication and adenoma detection rate. RESULTS: Of 31,856 colonoscopies, the adenoma prevalence was 26.1% for patients undergoing screening colonoscopy, 32.9% for patients with a history of polyps of unknown histology, and 41.9% for patients with a history of known adenomatous polyps. Relative to screening colonoscopies, there were higher odds of adenoma detection in surveillance colonoscopies for polyps of unknown histology (aOR compared to screening 1.42, 95% CI 1.30-1.55) and even higher odds among surveillance colonoscopies for a history of adenoma (aOR compared to screening 1.89, 95% CI 1.75-2.05). CONCLUSION: The adenoma prevalence on surveillance colonoscopy for patients with polyps of unknown histology was higher than that of screening colonoscopies but lower than that of surveillance colonoscopies for patients with adenomatous polyps.

Artificial Intelligence-Based Assessment of Colorectal Polyp Histology by Elastic-Scattering Spectroscopy.

BACKGROUND: Colonoscopic screening and surveillance for colorectal cancer could be made safer and more efficient if endoscopists could predict histology without the need to biopsy and perform histopathology on every polyp. Elastic-scattering spectroscopy (ESS), using fiberoptic probes integrated into standard biopsy tools, can assess, both in vivo and in real time, the scattering and absorption properties of tissue related to its underlying pathology. AIMS: The objective of this study was to evaluate prospectively the potential of ESS to predict polyp pathology accurately. METHODS: We obtained ESS measurements from patients undergoing screening/surveillance colonoscopy using an ESS fiberoptic probe integrated into biopsy forceps. The integrated forceps were used for tissue acquisition, following current standards of care, and optical measurement. All measurements were correlated to the index pathology. A machine learning model was then applied to measurements from 367 polyps in 169 patients to prospectively evaluate its predictive performance. RESULTS: The model achieved sensitivity of 0.92, specificity of 0.87, negative predictive value (NPV) of 0.87, and high-confidence rate (HCR) of 0.84 for distinguishing 220 neoplastic polyps from 147 non-neoplastic polyps of all sizes. Among 138 neoplastic and 131 non-neoplastic polyps ≤ 5 mm, the model achieved sensitivity of 0.91, specificity of 0.88, NPV of 0.89, and HCR of 0.83. CONCLUSIONS: Results show that ESS is a viable endoscopic platform for real-time polyp histology, particularly for polyps ≤ 5 mm. ESS is a simple, low-cost, clinically friendly, optical biopsy modality that, when interfaced with minimally obtrusive endoscopic tools, offers an attractive platform for in situ polyp assessment.

Filling in the "GAPPS": an unusual presentation of a child with gastric adenocarcinoma and proximal polyposis of the stomach.

Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) is a very rare gastric polyposis syndrome characterized by numerous polyps of the gastric fundus and body. We present the unusual case of a 10-year-old Polish-American male with history of eosinophilic esophagitis, who was found to have multiple fundic gland polyps (FGP) with low grade dysplasia on esophagogastroduodenoscopy. Subsequent evaluation including genetic testing confirmed the diagnosis of GAPPS, and after exhaustive multidisciplinary consultation the decision was made to proceed with prophylactic total gastrectomy given the markedly increased risk of gastric adenocarcinoma in GAPPS patients. To our knowledge, this represents the youngest patient diagnosed with GAPPS and the youngest patient who has undergone prophylactic gastrectomy for this disease at age 8 and 10 years, respectively. The pathophysiology, presentation, and treatment of GAPPS in a pediatric patient are discussed.

Prevalence of neoplasia in solitary and multiple esophago-gastrointestinal polyps: 5 years retrospective histopathological study.

The increasing use of endoscopy has led to more discernable abnormalities in the stomach, including polyps. Gastric polyps encompass a spectrum of pathologic conditions that can vary in histology, neoplastic potential, and management. Despite their high prevalence, there is a paucity of literature to support management and treatment decisions for endoscopists. The goal of this review is to summarize clinical, endoscopic, and histopathologic features of various polyps, review syndromes associated with such polyps and provide management recommendations. The present study was carried out for analyzing and comparing the prevalence of neoplasia in polyps (Solitary and multiple) removed endoscopically from the esophagus, stomach, and bowel undergoing screening. Five years retrospective study was done on patients who underwent endoscopy procedures including Oesophagogastroduodenoscopy (OGD) and colonoscopy between June 2015 and March 2019 in Faruk Medical City Hospital, Sulaimani City. Age and sex of patients, site of occurrence, number of polyps (solitary or multiple), and polyps' histologic type of 369 cases were analyzed in this study. Regarding solitary polyps, out of 279 polyps, 155 were neoplastic (55%) and 124 were non-neoplastic polyps, while multiple polyps, out of a total of 90 cases, 68 were neoplastic (75%) and 22 were non-neoplastic. More than 78% of patients were above the age of 40 years. Tubular adenoma was the most commonly diagnosed polyp. Large bowel was the most commonly involved site and left-sided polyps outnumbered right-sided ones with the sigmoid colon being the most commonly involved site. Screening programs including endoscopy, especially the colon for detecting polyps and particularly the colorectal region can be helpful to reduce morbidity and mortality of patients.

Filling the gap: A thorough investigation for the genetic diagnosis of unsolved polyposis patients with monoallelic MUTYH pathogenic variants.

BACKGROUNDS: MUTYH-associated polyposis (MAP) is an autosomal recessive disease caused by biallelic pathogenic variants (PV) of the MUTYH gene. The aim of this study was to investigate the genetic causes of unexplained polyposis patients with monoallelic MUTYH PV. The analysis focused on 26 patients with suspected MAP, belonging to 23 families. Ten probands carried also one or more additional MUTYH variants of unknown significance. METHODS: Based on variant type and on the collected clinical and molecular data, these variants were reinterpreted by applying the ACMG/AMP rules. Moreover, supplementary analyses were carried out to investigate the presence of other variants and copy number variations in the coding and promoter regions of MUTYH, as well as other polyposis genes (APC, NTHL1, POLE, POLD1, MSH3, RNF43, and MCM9). RESULTS: We reclassified 4 out of 10 MUTYH variants as pathogenic or likely pathogenic, thus supporting the diagnosis of MAP in only four cases. Two other patients belonging to the same family showed a previously undetected deletion of the APC gene promoter. No PVs were found in the other investigated genes. However, 6 out of the 18 remaining families are still interesting MAP candidates, due to the co-presence of a class 3 MUTYH variant that could be reinterpreted in the next future. CONCLUSION: Several efforts are necessary to fully elucidate the genetic etiology of suspected MAP patients, especially those with the most severe polyposis/tumor phenotype. Clinical data, tumor molecular profile, family history, and polyposis inheritance mode may guide variant interpretation and address supplementary studies.

Screening and prevention of colorectal cancer.

Mortality from colorectal cancer is reduced through screening and early detection; moreover, removal of neoplastic lesions can reduce cancer incidence. While understanding of the risk factors, pathogenesis, and precursor lesions of colorectal cancer has advanced, the cause of the recent increase in cancer among young adults is largely unknown. Multiple invasive, semi- and non-invasive screening modalities have emerged over the past decade. The current emphasis on quality of colonoscopy has improved the effectiveness of screening and prevention, and the role of new technologies in detection of neoplasia, such as artificial intelligence, is rapidly emerging. The overall screening rates in the US, however, are suboptimal, and few interventions have been shown to increase screening uptake. This review provides an overview of colorectal cancer, the current status of screening efforts, and the tools available to reduce mortality from colorectal cancer.

The Sulfur Microbial Diet Is Associated With Increased Risk of Early-Onset Colorectal Cancer Precursors.

BACKGROUND & AIMS: Diet may contribute to the increasing incidence of colorectal cancer (CRC) before age 50 (early-onset CRC). Microbial metabolism of dietary sulfur produces hydrogen sulfide (H2S), a gastrointestinal carcinogen that cannot be easily measured at scale. As a result, evidence supporting its role in early neoplasia is lacking. METHODS: We evaluated long-term adherence to the sulfur microbial diet, a dietary index defined a priori based on increased abundance of 43 bacterial species involved with sulfur metabolism, with risk of CRC precursors among 59,013 individuals who underwent lower endoscopy in the Nurses' Health Study II (1991-2015), a prospective cohort study with dietary assessment every 4 years through validated food frequency questionnaires and an assessment of dietary intake during adolescence in 1998. The sulfur microbial diet was characterized by intake high in processed meats, foods previously linked to CRC development, and low in mixed vegetables and legumes. Multivariable logistic regression for clustered data was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We documented 2911 cases of early-onset adenoma. After adjusting for established risk factors, higher sulfur microbial diet scores were associated with increased risk for early-onset adenomas (ORquartile [Q]4 vs Q1, 1.31; 95% CI, 1.10-1.56, Ptrend = .02), but not serrated lesions. Compared with the lowest, women in the highest quartile of sulfur microbial diet scores had significantly increased risk of early-onset adenomas with greater malignant potential (ORQ4 vs Q1, 1.65 for villous/tubulovillous histology; 95% CI, 1.12-2.43; Ptrend = .04). Similar trends for early-onset adenoma were observed based on diet consumed during adolescence. In contrast, no clear association for adenomas was identified after age 50. CONCLUSIONS: Our findings in a cohort of young women support a role for dietary interactions with gut sulfur-metabolizing bacteria in early-onset colorectal carcinogenesis, possibly beginning in adolescence.