Texture and Color Enhancement Imaging Improves Colonic Adenoma Detection: A Multicenter Randomized Controlled Trial.

The global burden of colorectal cancer is expected to increase more than 60% by 2030; however, compelling evidence now shows that the implementation of population screening programs in developed countries has led to a substantial reduction in incidence and mortality.1,2 Despite this, patients continue to develop preventable colorectal cancers, in part because of high rates of interval colon cancer diagnosed after screening or surveillance colonoscopies.3.

The multitarget faecal immunochemical test for improving stool-based colorectal cancer screening programmes: a Dutch population-based, paired-design, intervention study.

BACKGROUND: The faecal immunochemical test (FIT) is widely employed for colorectal cancer screening. However, its sensitivity for advanced precursor lesions remains suboptimal. The multitarget FIT (mtFIT), measuring haemoglobin, calprotectin, and serpin family F member 2, has demonstrated enhanced sensitivity for advanced neoplasia, especially advanced adenomas, at equal specificity to FIT. This study aimed to prospectively validate and investigate the clinical utlitity of mtFIT versus FIT in a setting of population-based colorectal cancer screening. METHODS: Individuals aged 55-75 years and who were eligible for the Dutch national FIT-based colorectal cancer screening programme were invited to submit both a FIT and mtFIT sample collected from the same bowel movement. Positive FIT (47 µg/g haemoglobin cutoff) or mtFIT (based on decision-tree algorithm) led to a colonoscopy referral. The primary outcome was the relative detection rate of mtFIT versus FIT for all advanced neoplasia. Secondary outcomes were the relative detection rates of colorectal cancer, advanced adenoma, and advanced serrated polyps individually and the long-term effect of mtFIT-based versus FIT-based programmatic screening on colorectal cancer incidence, mortality, and cost, determined with microsimulation modelling. The study has been registered in ClinicalTrials.gov, NCT05314309, and is complete. FINDINGS: Between March 25 and Dec 7, 2022, 35 786 individuals were invited to participate in the study, of whom 15 283 (42·7%) consented, and 13 187 (86·3%) of 15 283 provided both mtFIT and FIT samples with valid results. Of the 13 187 participants, 6637 (50·3%) were male and 6550 (49·7%) were female. mtFIT showed a 9·11% (95% CI 8·62-9·61) positivity rate and 2·27% (95% CI 2·02-2·54) detection rate for advanced neoplasia, compared with a positivity rate of 4·08% (3·75-4·43) and a detection rate of 1·21% (1·03-1·41) for FIT. Detection rates of mtFIT versus FIT were 0·20% (95% CI 0·13-0·29) versus 0·17% (0·11-0·27) for colorectal cancer; 1·64% (1·43-1·87) versus 0·86% (0·72-1·04) for advanced adenoma, and 0·43% (0·33-0·56) versus 0·17% (0·11-0·26) for advanced serrated polyps. Modelling demonstrated that mtFIT-based screening could reduce colorectal cancer incidence by 21% and associated mortality by 18% compared with the current Dutch colorectal cancer screening programme, at feasible costs. Furthermore, at equal positivity rates, mtFIT outperformed FIT in terms of diagnostic yield. At an equally low positivity rate, mtFIT-based screening was predicted to further decrease colorectal cancer incidence by 5% and associated mortality by 4% compared with FIT-based screening. INTERPRETATION: The higher detection rate of mtFIT for advanced adenoma compared with FIT holds the potential to translate into additional and clinically meaningful long-term colorectal cancer incidence and associated mortality reductions in programmatic colorectal cancer screening. FUNDING: Stand Up to Cancer, Dutch Cancer Society, Dutch Digestive Foundation, and Health~Holland.

A Comparison of Risk Classification Systems of Colorectal Adenomas: A Case-Cohort Study.

BACKGROUND & AIMS: Because post-polypectomy surveillance uses a growing proportion of colonoscopy capacity, more targeted surveillance is warranted. We therefore compared surveillance burden and cancer detection using 3 different adenoma classification systems. METHODS: In a case-cohort study among individuals who had adenomas removed between 1993 and 2007, we included 675 individuals with colorectal cancer (cases) diagnosed a median of 5.6 years after adenoma removal and 906 randomly selected individuals (subcohort). We compared colorectal cancer incidence among high- and low-risk individuals defined according to the traditional (high-risk: diameter ≥10 mm, high-grade dysplasia, villous growth pattern, or 3 or more adenomas), European Society of Gastrointestinal Endoscopy (ESGE) 2020 (high-risk: diameter ≥10 mm, high-grade dysplasia, or 5 or more adenomas), and novel (high-risk: diameter ≥20 mm or high-grade dysplasia) classification systems. For the different classification systems, we calculated the number of individuals recommended frequent surveillance colonoscopy and estimated number of delayed cancer diagnoses. RESULTS: Four hundred and thirty individuals with adenomas (52.7%) were high risk based on the traditional classification, 369 (45.2%) were high risk based on the ESGE 2020 classification, and 220 (27.0%) were high risk based on the novel classification. Using the traditional, ESGE 2020, and novel classifications, the colorectal cancer incidences per 100,000 person-years were 479, 552, and 690 among high-risk individuals, and 123, 124, and 179 among low-risk individuals, respectively. Compared with the traditional classification, the number of individuals who needed frequent surveillance was reduced by 13.9% and 44.2%, respectively, and 1 (3.4%) and 7 (24.1%) cancer diagnoses were delayed using the ESGE 2020 and novel classifications. CONCLUSIONS: Using the ESGE 2020 and novel risk classifications will substantially reduce resources needed for colonoscopy surveillance after adenoma removal.

Low Colorectal Cancer Risk After Resection of High-Risk Pedunculated Polyps.

BACKGROUND: Post-fecal immunochemical test (FIT) colonoscopy represents a setting with an enriched prevalence of advanced adenomas. Due to an expected higher risk of colorectal cancer (CRC), postpolypectomy surveillance is recommended, generating a substantially increased load on endoscopy services. The aim of our study was to investigate postpolypectomy CRC risk in a screening population of FIT+ subjects after resection of low-risk adenomas (LRAs) or high-risk adenomas (HRAs). METHODS: We retrieved data from a cohort of patients undergoing postpolypectomy surveillance within a FIT-based CRC screening program in Italy between 2002 and 2017 and followed-up to December 2021. Main outcomes were postpolypectomy CRC incidence and mortality risks according to type of adenoma (LRA/HRA) removed at colonoscopy as well as morphology, size, dysplasia, and location of the index lesion. We adopted as comparators FIT+/colonoscopy-negative and FIT- patients. The absolute risk was calculated as the number of incident CRCs per 100,000 person-years of follow-up. We used Cox multivariable regression models to identify associations between CRC risks and patient- and polyp-related variables. RESULTS: Overall, we included 87,248 post-FIT+ colonoscopies (133 endoscopists). Of these, 42,899 (49.2%) were negative, 21,650 (24.8%) had an LRA, and 22,709 (26.0%) an HRA. After a median follow-up of 7.25 years, a total of 635 CRCs were observed. For patients with LRAs, CRC incidence (hazard ratio [HR], 1.18; 95% confidence interval [CI], 0.92-1.53) was not increased compared with the FIT+/colonoscopy-negative group, while for HRAs a significant increase in CRC incidence (HR, 1.53; 95% CI, 1.14-2.04) was found. The presence of 1 or more risk factors among proximal location, nonpedunculated morphology, and high-grade dysplasia explained most of this excess CRC risk in the HRA group (HR, 1.85; 95% CI, 1.36-2.52). Patients with only distal pedunculated polyps without high-grade dysplasia, representing 39.2% of HRA, did not have increased risk compared with the FIT- group (HR, 0.87; 95% CI, 0.59-1.28). CONCLUSIONS: CRC incidence is significantly higher in patients with HRAs diagnosed at colonoscopy. However, such excess risk does not appear to apply to patients with only distal pedunculated polyps without high-grade dysplasia, an observation that could potentially reduce the burden of surveillance in FIT programs.

Adenomas and Sessile Serrated Lesions in 45- to 49-Year-Old Individuals Undergoing Colonoscopy: A Systematic Review and Meta-Analysis.

INTRODUCTION: Colorectal cancer (CRC) screening is now recommended at the age of 45 years in the United States. However, information regarding the adenomas detection rate (ADR) and sessile serrated lesions (SSLs) in 45- to 49-year-old individuals is limited. In addition, the impact of lowering the screening age to 45 years on the ADR and the detection rate of SSLs is not well elucidated. This systematic review and meta-analysis aims to report the overall ADR and SSL detection rate in 45- to 49-year-old individuals undergoing colonoscopy. METHODS: We searched MEDLINE, EMBASE, SCOPUS, Web of Science, ClinicalTrials.gov , and the Cochrane database from inception through October 2022 to identify studies reporting on ADR and SSL detection rates in 45- to 49-year-old individuals undergoing colonoscopies for all indications. This approach acknowledges the possibility of including individuals undergoing diagnostic colonoscopies or those with increased risk factors for CRC. We also conducted a separate analysis examining ADR in average-risk individuals undergoing screening colonoscopy. The pooled rates with their corresponding 95% confidence intervals (CIs) were generated using the fixed-effects model. I2 was used to adjudicate heterogeneity. RESULTS: Sixteen studies met the inclusion criteria. All studies were retrospective except one; 3 had data from national/local registries. There were 41,709 adenomas detected across 150,436 colonoscopies. The pooled overall ADR was 23.1% (95% CI 19.7%-27.0%, I2 = 98.6%). The pooled ADR in individuals with average risk of CRC from 7 studies was 28.2% (95% CI 24.6%-32.0%, I2 = 96.5%). The pooled overall SSL detection rate from 6 studies was 6.3% (95% CI 3.8%-10.5%, I2 = 97%). The included studies were heterogeneous because of differences in the inclusion and exclusion criteria and patient population. DISCUSSION: In 45- to 49-year-old individuals undergoing a colonoscopy for any indication, the ADR and SSL detection rates were 23.1% and 6.3%, respectively. We conclude that these outcomes in 45- to 49-year-olds are comparable with individuals aged 50-54 years.

Risk factors for advanced colorectal neoplasia and colorectal cancer detected at surveillance: a nationwide study in the modern era.

AIM: Recommendations for surveillance after colonoscopy are based on risk factors for metachronous advanced colorectal neoplasia (AN) and colorectal cancer (CRC). The value of these risk factors remains unclear in populations enriched by individuals with a positive faecal immunochemical test and were investigated in a modern setting. METHODS AND RESULTS: This population-based cohort study included all individuals in the Netherlands of ≥55 years old with a first adenoma diagnosis in 2015. A total of 22,471 patients were included. Data were retrieved from the Dutch Nationwide Pathology Databank (Palga). Primary outcomes were metachronous AN and CRC. Patient and polyp characteristics were evaluated by multivariable Cox regression analyses. During follow-up, 2416 (10.8%) patients were diagnosed with AN, of which 557 (2.5% from the total population) were CRC. Adenomas with high-grade dysplasia (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.40-1.83), villous histology (HR 1.91, 95% CI 1.59-2.28), size ≥10 mm (HR 1.12, 95% CI 1.02-1.23), proximal location (HR 1.12, 95% CI 1.02-1.23), two or more adenomas (HR 1.28, 95% CI 1.16-1.41), and serrated polyps ≥10 mm (HR 1.67, 95% CI 1.42-1.97) were independent risk factors for metachronous AN. In contrast, only adenomas with high-grade dysplasia (HR 2.49, 95% CI 1.92-3.24) were an independent risk factor for metachronous CRC. CONCLUSIONS: Risk factors for metachronous AN and CRC were identified for populations with access to a faecal immunochemical test (FIT)-based screening programme. If only risk factors for metachronous CRC are considered, a reduction in criteria for surveillance seems reasonable.

Differences between men and women with respect to colorectal cancer mortality despite screening colonoscopy.

BACKGROUND AND AIMS: Women aged 55 to 59 years have a similar prevalence rate and number needed to screen for colorectal adenomas as men at a 10-year younger age. The aim of this study was to determine sex-specific differences in colorectal cancer mortality and estimate the association with adenomas at screening colonoscopy. METHODS: This retrospective study analyzed 323,139 individuals who underwent colonoscopy within a national colorectal cancer screening program in Austria between January 2007 and December 2020. RESULTS: Median patient age was 60 years (interquartile range, 54-67), and the sex distribution in all age groups was nearly identical. Men had significantly higher odds of having an adenoma or serrated polyp, low-risk polyp, high-risk polyp, or colorectal cancer detected at colonoscopy than women (odds ratio [OR] 1.83; 95% confidence interval [CI], 1.80-1.86; OR, 1.46; 95% CI, 1.44-1.49; OR, 1.74; 95% CI, 1.69-1.80; and OR, 1.87; 95% CI, 1.70-2.05, respectively). Strikingly, male sex, when compared with female sex, was associated with an almost 2-fold (hazard ratio, 1.67; 95% CI, 1.05-2.67) increased risk to die from colorectal cancer when an adenoma or serrated polyp was found at the screening colonoscopy and a 4-fold (hazard ratio, 4.14; 95% CI, 2.72-6.3) increased risk when a high-risk polyp was found at the screening colonoscopy. The cumulative incidence for death of colorectal cancer for 60-year-old individuals was 8.5-fold higher in men as compared with women. Markedly, this sex gap narrowed with increasing age, whereas the difference in deaths of other causes remained similar in all age groups. CONCLUSIONS: Our findings strengthen the necessity of sex-specific screening recommendations. Importantly, further prospective studies should focus on sex differences in tumor biology to propose personalized surveillance guidelines.

Risk factors for metachronous colorectal cancer or advanced lesions after endoscopic resection of serrated polyps: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Serrated polyps (SPs) are precursors to 15% to 20% of colorectal cancers (CRCs). However, there are uncertainties regarding which SPs require surveillance and at what intervals, with recommendations adapted from those for adenomas in the absence of solid evidence. Our aim was to assess which SP risk characteristics relate to a higher risk of metachronous CRC or advanced polyps. METHODS: We systematically searched PubMed, Embase, and Cochrane for cohort studies, case-control studies, and clinical trials from inception to December 31, 2023, of CRC or advanced polyps (advanced adenoma [AA] or advanced SP) incidence at surveillance stratified by baseline SP size, dysplasia, location, and multiplicity. We defined advanced SPs as those ≥10 mm or with dysplasia. CRC and advanced polyp incidence per 1000 person-years were estimated. We performed a meta-analysis by calculating pooled relative risks (RRs) using a random-effects model. RESULTS: A total of 5903 studies were reviewed, and 14 were included with 493,949 patients (mean age, 59.5 years; 55% men). The mean follow-up was 4.9 years. CRC incidence per 1000 person-years was 2.09 (95% confidence interval [CI], 1.29-2.90) for advanced SPs, 1.52 (95% CI, 0.78-2.25) for SPs of ≥10 mm, 5.86 (95% CI, 2.16-9.56) for SPs with dysplasia, 1.18 (95% CI, 0.77-1.60) for proximal SPs, 0.52 (95% CI, 0.08-1.12) for ≥3 SPs, 0.50 (95% CI, 0.35-0.66) for nonadvanced SPs, and 0.44 (95% CI, 0.41-0.46) for normal colonoscopy findings. Metachronous CRC risk was higher in advanced SPs versus nonadvanced SPs (RR, 1.84; 95% CI, 1.11-3.04) and versus normal colonoscopy findings (RR, 2.92; 95% CI, 2.26-3.77), in SPs of ≥10 mm versus <10 mm (RR, 2.61; 95% CI, 1.43-4.77) and versus normal colonoscopy findings (RR: 3.52; 95% CI, 2.17-5.69); and in SPs with dysplasia versus normal colonoscopy findings (RR: 2.71; 95% CI, 2.00-3.67). No increase in CRC or advanced polyp risk was found in patients with proximal versus distal SPs, nor in ≥3 SPs versus 1 or 2 SPs. CONCLUSIONS: CRC risk is significantly higher in patients with baseline advanced SPs after 4.9 years of follow-up, with risk magnitudes similar to those described for AA, supporting the current recommendation for 3-year surveillance in patients with advanced SPs.

Prevalence and predictive factors of colorectal sessile serrated lesions in younger individuals.

BACKGROUND: Sessile serrated lesions (SSLs) are obscured lesions predominantly in the right-sided colon and associated with interval colorectal cancer; however, their prevalence and risk factors among younger individuals remain unclear. METHODS: This retrospective study enrolled individuals who underwent index colonoscopy. The primary outcome was the SSL prevalence in the younger (<50 years) and older (≥50 years) age groups, while the secondary outcomes included clinically significant serrated polyps (CSSPs). Multivariable logistic regression was employed to identify predictors. RESULTS: Of the 9854 eligible individuals, 4712 (47.8%) were categorized into the younger age group. Individuals in the younger age group exhibited lower prevalences of adenomas (22.6% vs. 46.2%; P<0.001) and right-sided adenomas (11.2% vs. 27.2%; P<0.001) compared with their older counterparts. However, both groups exhibited a similar prevalence of SSLs (7.2% vs. 6.5%; P=0.16) and CSSPs (10.3% vs. 10.3%;P=0.96). Multivariable analysis revealed that age 40-49 years (odds ratio [OR] 1.81, 95%CI 1.01-3.23), longer withdrawal time (OR 1.17, 95%CI 1.14-1.20, per minute increment), and endoscopist performance (OR 3.35, 95%CI 2.44-4.58) were independent predictors of SSL detection in the younger age group. No significant correlation was observed between adenoma and SSL detection rates among endoscopists. CONCLUSION: SSLs are not uncommon among younger individuals. Moreover, diligent effort and expertise are of paramount importance in SSL detection. Future studies should explore the clinical significance of SSLs in individuals of younger age.

Sessile serrated lesion prevalence and factors associated with their detection: a post-hoc analysis of a multinational randomized controlled trial from Asia.

BACKGROUND: Sessile serrated lesions (SSLs) are associated with an increased risk of colorectal cancer. Data on the prevalence of SSLs in Asia are limited. We performed this study to estimate the prevalence of SSLs in Asia and to explore endoscopic factors that are associated with SSL detection. METHODS: This is a post-hoc analysis of a multicenter randomized controlled trial from four Asian countries/regions that compared adenoma detection rates using linked-color imaging (LCI) and white-light imaging. Colonoscopies were performed in an average-risk population for screening, diagnostic examination, or polyp surveillance. Patients with SSLs were compared against those without SSLs to evaluate for possible predictors of SSL detection using Firth's logistic regression. RESULTS: 2898 participants (mean age 64.5 years) were included in the analysis. The estimated prevalence of SSLs was 4.0% (95%CI 3.4%-4.8%), with no sex or age group differences. On multivariable analysis, use of LCI (adjusted odds ratio [aOR] 1.63, 95%CI 1.10-2.41), experienced endoscopists (aOR 1.94, 95%CI 1.25-3.00), use of transparent cap (aOR 1.75, 95%CI 1.09-2.81), and longer withdrawal time (aOR 1.06, 95%CI 1.03-1.10) were independently associated with SSL detection. Synchronous adenoma detection (aOR 1.89, 95%CI 1.20-2.99) was also predictive of SSL detection. CONCLUSION: The prevalence of SSLs in Asia is 4.0%. Use of LCI or a transparent cap, greater endoscopist experience, and longer withdrawal time were all associated with increased SSL detection.

Diverticulosis, Adenomas, and Cancer in the Colon: A Systematic Review and Meta-Analysis of Endoscopic Studies.

GOALS: To perform a systematic review and meta-analysis of endoscopic studies to evaluate an association between diverticulosis and neoplastic lesions in the colon. BACKGROUND: Some epidemiological observations suggest an association between diverticulosis and adenoma/cancer in the colon. However, an increased risk of colon neoplastic lesions in diverticulosis subjects was found to be increased in some studies, but not in others, puzzling data interpretation. STUDY: From the retrieved studies, prevalence of adenomas, advanced adenomas, cancer or neoplasia (advanced adenoma or cancer) was compared between subjects with or without diverticulosis, and comparisons in subgroups were also performed. RESULTS: Data of 26 studies with a total of 419,623 patients were eventually considered, including 27,092 patients with diverticulosis. Data analysis found a statistically significant association between diverticulosis and adenomas (OR: 1.88; 95% CI: 1.50-2.25), advanced adenomas (OR: 1.49; 95% CI: 1.02-2.16), and neoplasia (OR: 1.50; 95% CI: 1.11-2.02), but not with cancer alone (OR: 1.01; 95% CI: 0.70-1.47). These associations were confirmed in the subgroup analyses, by considering Caucasian and Asian populations, prospective and retrospective studies, screening or symptoms settings, and between good or fair quality studies. CONCLUSIONS: A statistically significant association between diverticulosis and adenomas, advanced adenomas and neoplasia, but not with cancer alone was found. However, the strength of association seems to be insufficient to impact on clinical practice.

Risk Factors Associated with Advanced Colorectal Neoplasia in Adults Younger than Age 45.

BACKGROUND: Colorectal cancer (CRC) is rising in young adults between ages 20 to 49 years. CRC screening is endorsed for average-risk individuals beginning at ages 45 to 49 years. Targeting screening for individuals <45 years may be warranted if risk factors for advanced neoplasia can be identified. AIM: To identify factors associated with advanced colorectal neoplasia in adults aged <45 years. METHOD: Individuals ages 18 to 44 years who underwent colonoscopy at Cleveland Clinic between 2011 and 2021 with ≥1 advanced neoplasm (AN) were included. Patients with inflammatory bowel disease or inherited CRC syndromes were excluded. Demographics, comorbidities, family history of CRC, and colonoscopy indication were obtained. Patients with a normal colonoscopy constituted the control group. A multivariable logistic regression model was used to investigate the relationship between clinical variables and the presence of advanced colorectal neoplasia. RESULTS: In all, 13,006 patients were included, of which 651 (5%) patients had AN: 404 (62%) with tubular adenoma ≥10 mm, 29 (4.5%) tubular adenoma with high-grade dysplasia, 210 (32%) tubulovillous adenomas, 27 (4%) traditional serrated adenomas, 82 (13%) sessile serrated lesions ≥10 mm, 7(2%) sessile serrated lesions with dysplasia, and 29 (4.4%) patients had a CRC. Factors associated with AN were older age (means 38.5 vs. 36.6 y), history of smoking, diabetes, non-White race, higher body mass index (29.9 vs. 28.5 kg/m 2 ), and lower vitamin D (27.6 vs. 32.2 ng/dl), all P <0.001. In the reduced multivariable model, factors associated with AN included tobacco use (OR 2.026 (current vs. never, P <0.0001), age (OR increase by 1.06 per year, P <0.0001), male gender (OR 1.476, P <0.0001), family history of CRC (OR 3.91, P <0.0001), aspirin use (1.31, P =0.035), and diabetes (OR 2.106, P 0.001). CONCLUSION: Increasing age, male gender, exposure to tobacco, family history of CRC, diabetes, and aspirin use were independently associated with advanced neoplasia in adults younger than 45. Targeted early screening to young adults with these risk factors may be justified. Large collaborative prospective studies are needed to validate our findings.

MAFLD with central obesity is associated with increased risk of colorectal adenoma and high-risk adenoma.

OBJECTIVE: To analyze the risk factors associated with colorectal adenoma and to investigate the associations of metabolism-related fatty liver disease (MAFLD) with obesity, colorectal adenoma and high-risk adenoma. METHODS: A total of 1395 subjects were enrolled and divided into a colorectal adenoma group (593 subjects) and a control group (802 subjects) according to the inclusion and exclusion criteria. The characteristics of patients in the colorectal adenoma group and the control group were compared by the chi-square test. Univariate and multivariate logistic analyses were used to analyze independent risk factors and associations with different MAFLD subtypes. Colorectal adenoma characteristics and the proportion of patients with high-risk colorectal adenoma were also compared. RESULTS: High-density lipoprotein (HDL-C) was significantly lower in patients in the colorectal adenoma group than in those in the control group (P < 0.001). Logistic regression analysis revealed that age, obesity status, central obesity status, hypertension status, diabetes status, fatty liver status, smoking history, BMI, waist circumference, triglyceride level, HDL-C level, fasting blood glucose level and degree of hepatic steatosis were all independent risk factors for colorectal adenoma. Notably, MAFLD was associated with a significantly increased risk of colorectal adenoma in patients with central obesity (P < 0.001). In addition, obesity, central obesity, diabetes, fatty liver and degree of hepatic steatosis were all shown to be independent risk factors for high-risk colorectal adenoma. In addition, a greater proportion of MAFLD patients with central obesity than those without central obesity had high-risk colorectal adenoma. CONCLUSION: MAFLD and central obesity are independently associated with the development of colorectal adenoma. MAFLD with central obesity is associated with an increased risk of colorectal adenoma and high-risk adenoma.

Characteristics and Prognosis of Sporadic Neoplasias Detected in Patients with Ulcerative Colitis.

INTRODUCTION: Patients with ulcerative colitis (UC) develop not only UC-associated neoplasias but also sporadic neoplasias (SNs). However, few studies have described the characteristics of SNs in patients with UC. Therefore, this study aimed to evaluate the clinical features and prognosis of SNs in patients with UC. METHODS: A total of 141 SNs in 59 patients with UC, detected by surveillance colonoscopy at Hiroshima University Hospital between January 1999 and December 2021, were included. SNs were diagnosed based on their location, endoscopic features, and histopathologic findings along with immunohistochemical staining for Ki67 and p53. RESULTS: Of the SNs, 91.5% were diagnosed as adenoma and 8.5% were diagnosed as carcinoma (Tis carcinoma, 3.5%; T1 carcinoma, 5.0%). 61.0% of the SNs were located in the right colon, 31.2% were located in the left colon, and 7.8% were located in the rectum. When classified based on the site of the lesion, 70.9% of SNs occurred outside and 29.1% within the affected area. Of all SNs included, 95.7% were endoscopically resected and 4.3% were surgically resected. Among the 59 patients included, synchronous SNs occurred in 23.7% and metachronous multiple SNs occurred in 40.7% during surveillance. The 5-year cumulative incidence of metachronous multiple SNs was higher in patients with synchronous multiple SNs (54.2%) than in those without synchronous multiple SNs (46.4%). CONCLUSION: Patients with UC with synchronous multiple SNs are at a higher risk of developing metachronous multiple SNs and may require a closer follow-up by total colonoscopy than patients without synchronous SNs.

Risk of advanced neoplasia after removal of colorectal adenomas with high-grade dysplasia.

BACKGROUND: Many studies reported the presence of adenomas with high-grade dysplasia (HGD) at index colonoscopy increased the incidence of advanced neoplasia (AN) and colorectal cancer (CRC) following. However, the conclusion remains obscure due to lack of studies on the specific population of adenomas with HGD. This study aimed to assess the long-term risk of AN and CRC after removal of adenomas with HGD. METHODS: A total of 814 patients who underwent adenomas with HGD removal between 2010 and 2019 were retrospectively analyzed. The outcomes were the incidences of AN and CRC during surveillance colonoscopy. Cox proportional hazards models were utilized to identify risk factors associated with AN and CRC. RESULTS: During more than 2000 person-years of follow-up, we found that AN and CRC incidence densities were 44.3 and 4.4 per 1000 person-years, respectively. The 10-year cumulative incidence of AN and CRC were 39.1% and 5.5%, respectively. In the multivariate model, synchronous low-risk polyps (HR 1.80, 95% CI 1.10-2.93) and synchronous high-risk polyps (HR 3.99, 95% CI 2.37-6.72) were risk factors for AN, whereas participation in surveillance colonoscopy visits (HR 0.56, 95% CI 0.36-0.88 for 1 visit; HR 0.10, 95% CI 0.06-0.19 for ≥ 2 visits) were associated with decreased AN incidence. Additionally, elevated baseline carcinoembryonic antigen (CEA) level (HR 10.19, 95% CI 1.77-58.59) was a risk factor for CRC, while participation in ≥ 2 surveillance colonoscopy visits (HR 0.11, 95% CI 0.02-0.56) were associated with decreased CRC incidence. Interestingly, for 11 patients who developed CRC after removal of adenomas with HGD, immunohistochemistry revealed that 8 cases (73%) were deficient mismatch repair CRCs. CONCLUSIONS: Patients who have undergone adenoma with HGD removal are at higher risk of developing AN and CRC, while surveillance colonoscopy can reduce the risk. Patients with synchronous polyps, or with elevated baseline CEA level are considered high-risk populations and require more frequent surveillance.

Serrated Polyps in Inflammatory Bowel Disease Indicate a Similar Risk of Metachronous Colorectal Neoplasia as in the General Population.

BACKGROUND: The risk of metachronous advanced neoplasia after diagnosing serrated polyps in patients with IBD is poorly understood. METHODS: A retrospective multicenter cohort study was conducted between 2010 and 2019 at three tertiary centers in Montreal, Canada. From pathology databases, we identified 1587 consecutive patients with serrated polyps (sessile serrated lesion, traditional serrated adenoma, or serrated epithelial change). We included patients aged 45-74 and excluded patients with polyposis, colorectal cancer, or no follow-up. The primary outcome was the risk of metachronous advanced neoplasia (advanced adenoma, advanced serrated lesion, or colorectal cancer) after index serrated polyp, comparing patients with and without IBD. RESULTS: 477 patients with serrated polyps were eligible (mean age 61 years): 37 with IBD, totaling 45 serrated polyps and 440 without IBD, totaling 586 serrated polyps. The median follow-up was 3.4 years. There was no difference in metachronous advanced neoplasia (HR 0.77, 95% CI 0.32-1.84), metachronous advanced adenoma (HR 0.54, 95% CI 0.11-2.67), and metachronous advanced serrated lesion (HR 0.76, 95% CI 0.26-2.18) risk. When comparing serrated polyps in mucosa involved or uninvolved with IBD, both groups had similar intervals from IBD to serrated polyp diagnosis (p > 0.05), maximal therapies (p > 0.05), mucosal inflammation, inflammatory markers, and fecal calprotectin (p > 0.05). CONCLUSION: The risk of metachronous advanced neoplasia after serrated polyp detection was similar in patients with and without IBD. Serrated polyps in IBD occurred independently of inflammation. This helps inform surveillance intervals for patients with IBD diagnosed with serrated polyps.

Exogenous Insulin Therapy Is Associated with the Risk of Advanced Colorectal Adenoma in Patients with Diabetes Mellitus.

BACKGROUND/AIMS: Exogenous insulin therapy increases systemic exposure to insulin which may promote the development of colorectal neoplasia. We sought to evaluate the association between exogenous insulin therapy and the incidence of advanced adenoma in type 2 diabetes mellitus. METHODS: A retrospective cohort study was conducted from January 1, 2007, to January 1, 2018, in a regional health system serving the United States Philadelphia metropolitan area, Central New Jersey, and South Central Pennsylvania. Study patients consisted of a random sample of patients with type 2 diabetes mellitus aged 40-80 years who had undergone two rounds of colonoscopy examinations. The exposure was cumulative duration of insulin therapy (i.e., no use, 1-365 days and > 365 days). The outcome was time to incident advanced adenoma. RESULTS: Of the 975 eligible patients, 184 patients accumulated > 365 days of insulin therapy before the follow-up colonoscopy. The mean (standard deviation) duration between the two rounds of colonoscopy examination was 5.1 (2.9) years among the insulin users and 5.3 (3.9) years among non-users. Compared to no insulin exposure, receiving > 365 days of insulin therapy was associated with an increased incidence of advanced adenoma (adjusted hazard ratio [aHR] 4.84, 95% confidence interval [CI] 2.82-8.30), right-sided advanced adenoma (aHR 5.48, 95% CI 2.90-10.35), and 3 or more adenomas (aHR 2.61, 95% CI 1.46-4.69) at the follow-up colonoscopy examination. CONCLUSION: Insulin therapy is associated with an increased risk of advanced adenoma and may serve as a novel risk-stratification factor to enhance the efficiency of existing colorectal cancer screening and surveillance programs.

Pituitary apoplexy: a systematic review of non-gestational risk factors.

PURPOSE: Pregnancy is a known risk factor for Pituitary Apoplexy (PA) but there is a lack of consistency in the literature regarding non-gestational risk factors responsible for PA. METHODS: We did a systematic review following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to identify the non-gestational risk factors associated with the development of PA in adult patients with pituitary adenoma. Also, we discuss here a case of an elderly female with pituitary macroadenoma who was initially planned for pituitary resection electively but underwent emergency surgery after she developed PA. RESULTS: As per screening and eligibility criteria, seven studies with 4937 study participants were included in this systematic review out of which 490 (9.92%) patients had PA, including asymptomatic subclinical PA (SPA) and symptomatic clinical PA (CPA). The macroadenomas and negative staining of the tumor were found to be a significant risk factor consistently in multivariate analysis in three and two retrospective studies, respectively. However, the results were varied for any significant difference in the risk factors for apoplexy between SPA and CPA. Similarly, there was no consistency among the studies for risk factors significantly responsible for CPA or PA compared to controls. CONCLUSION: No single non-gestational risk factor is solely responsible for the development of PA in a pituitary adenoma compared to the control population. Tumor size (macroadenoma) and the non-functioning status of the adenoma are the only significant factors contributing independently toward an apoplectic event in most patients. Such patients can be prioritized for early pituitary tumor resection.

High prevalence of morphometric vertebral fractures opportunistically detected on thoracic radiograms in patients with non-functioning pituitary adenoma.

PURPOSE: Vertebral fractures (VFs), the hallmark of skeletal fragility, have been reported as an emerging complication in patients with pituitary diseases associated with hormonal excess and/or deficiency, independently from bone mineral density. Non-functioning pituitary adenoma (NFPA) is amongst the most frequent pituitary adenomas; however, skeletal health in this context has never been investigated. We aimed at assessing the prevalence and the determinants of morphometric VFs in patients with NFPA. METHODS: We enrolled 156 patients (79 M/77F, mean age 55.75 ± 12.94 years) at admission in Neurosurgery Unit before trans-sphenoidal surgery and compared them with an age and sex-matched control group of subjects with neither history/risk factors for secondary osteoporosis nor pituitary disorders. We performed a vertebral morphometric evaluation of the thoracic spine on pre-operative X-ray images (MTRx) and collected biochemical, demographic, and clinical data from the entire cohort. RESULTS: The prevalence of thoracic VFs in patients with NFPA was significantly higher than the control group (26.3% vs. 10.3%; p < 0.001). In the NFPA group, 20 patients (48.8% of the fractured patients) showed multiple VFs, 14 (34.1% of them) showed moderate/severe VFs. Patients with VFs were significantly older and had lower serum free triiodothyronine (fT3) levels than non-fractured ones (p = 0.002 and p = 0.004; respectively). The prevalence of secondary male hypogonadism was higher among men with VFs as compared to those with no VFs (72% vs. 48.1%; p = 0.047). Consistently, total testosterone levels in males were significantly lower in fractured patients than in non-fractured ones (p = 0.02). The prevalence of gonadotroph adenomas was significantly higher among patients with VFs (p = 0.02). In multiple logistic regression analysis, older age and lower serum fT3 levels were independent factors predicting the risk for VFs. CONCLUSIONS: For the first time, we reported a high prevalence of thoracic radiological VFs in patients with NFPAs. Our data should prompt clinicians to proceed with a clinical bone fragility evaluation already during the diagnostic work-up, particularly in those with concomitant hypogonadism, or in those with older age and/or with lower fT3.

Recurrence in acromegaly: two tertiary centers experience and review of the literature.

BACKGROUND: Recurrence of acromegaly after successful surgery is a rare event, but no clear data are reported in the literature about its recurrence rates. This study aimed to evaluate the recurrence rate in a series of acromegalic patients treated by transsphenoidal surgery (TSS) with a long follow-up. METHODS: We retrospectively analyzed data from 283 acromegalic patients who underwent TSS at two pituitary units in Milan (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and IRCCS Humanitas Research Hospital). The diagnosis and recurrence of acromegaly were defined by both elevated IGF-1 levels and a lack of GH suppression based on appropriate criteria for the assay used at the time of diagnosis. RESULTS: After surgery, 143 patients (50%) were defined as not cured, 132 (47%) as cured and 8 (3%) as partially cured because of normalization of only one parameter, either IGF1 or GH. In the cured group, at the last follow-up (median time 86.8 months after surgery), only 1 patient (0.7%) showed full recurrence (IGF-1 + 5.61 SDS, GH nadir 1.27 µg/l), while 4 patients (3%) showed only increased IGF1. In the partially cured group at the last follow-up, 2/8 (25%) patients showed active acromegaly (IGF-1 SDS + 2.75 and + 3.62; GH nadir 0.6 and 0.5 µg/l, respectively). CONCLUSIONS: In the literature, recurrence rates range widely, from 0 to 18%. In our series, recurrence occurred in 3.7% of patients, and in fewer than 1%, recurrence occurred with elevation of both IGF-1 and the GH nadir. More frequently (25%), recurrence came in the form of incomplete normalization of either IGF-1 or GH after surgery.