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Inflammatory bowel disease [IBD] patients are at increased risk of developing colorectal neoplasia [CRN]. In this review, we aim to provide an up-to-date overview and future perspectives on CRN management in IBD. Advances in endoscopic surveillance and resection techniques have resulted in a shift towards endoscopic management of neoplastic lesions in place of surgery. Endoscopic treatment is recommended for all CRN if complete resection is feasible. Standard [cold snare] polypectomy, endoscopic mucosal resection and endoscopic submucosal dissection should be performed depending on lesion complexity [size, delineation, morphology, surface architecture, submucosal fibrosis/invasion] to maximise the likelihood of complete resection. If complete resection is not feasible, surgical treatment options should be discussed by a multidisciplinary team. Whereas [sub]total and proctocolectomy play an important role in management of endoscopically unresectable CRN, partial colectomy may be considered in a subgroup of patients in endoscopic remission with limited disease extent without other CRN risk factors. High synchronous and metachronous CRN rates warrant careful mucosal visualisation with shortened intervals for at least 5 years after treatment of CRN. [ABSTRACT FROM AUTHOR]

Data on the frequency of colorectal neoplasia in sporadic ampullary tumors remains scarce. We retrospectively reviewed 135 patients undergoing endoscopic ampullectomy from January 2018 to July 2021, and identified 95 patients with sporadic ampullary adenoma who underwent total colonoscopy. Colonoscopy findings were compared with 380 asymptomatic controls using the chi-squared test. Whole-exome sequencing (WES) was performed on one patient with synchronous adenomas of the ampulla of Vater and ascending colon. Colorectal polyps were present in 60% of Cases vs. 34.7% of Controls (P = 0.001), advanced adenoma in 20% vs. 5.5%, and adenocarcinoma in 4.2% vs. 0.8%. Cases tended to have larger polyps than Controls (P <0.001), while there was no difference in polyp location and histology between the two groups. The odds ratio of all the colorectal lesions, advanced colorectal adenoma and adenocarcinoma in C ases was 1.7, 4.2, and 4, respectively. WES in one patient revealed that both of ampullary adenoma and colonic adenoma shared somatic ABCB1 mutation. The frequency of colorectal polyps or neoplasia was significantly higher in Cases than Controls. We proposed that ampullary neoplasia is analogous to colon lesions and warrants total colonoscopy screening in patients diagnosed with ampullary tumors. [ABSTRACT FROM AUTHOR]

Objective: We aimed to examine associations between the oral, fecal, and mucosal microbiome communities and adenoma formation. Summary Background Data: Data are limited regarding the relationships between microbiota and preneoplastic colorectal lesions. Methods: Individuals undergoing screening colonoscopy were prospectively enrolled and divided into adenoma and nonadenoma formers. Oral, fecal, nonadenoma and adenoma-adjacent mucosa were collected along with clinical and dietary information. 16S rRNA gene libraries were generated using V4 primers. DADA2 processed sequence reads and custom R-scripts quantified microbial diversity. Linear regression identified differential taxonomy and diversity in microbial communities and machine learning identified adenoma former microbial signatures. Results: One hundred four subjects were included, 46% with adenomas. Mucosal and fecal samples were dominated by Firmicutes and Bacteroidetes whereas Firmicutes and Proteobacteria were most abundant in oral communities. Mucosal communities harbored significant microbial diversity that was not observed in fecal or oral communities. Random forest classifiers predicted adenoma formation using fecal, oral, and mucosal amplicon sequence variant (ASV) abundances. The mucosal classifier reliably diagnosed adenoma formation with an area under the curve (AUC) = 0.993 and an out-of-bag (OOB) error of 3.2%. Mucosal classifier accuracy was strongly influenced by five taxa associated with the family Lachnospiraceae, genera Bacteroides and Marvinbryantia, and Blautia obeum. In contrast, classifiers built using fecal and oral samples manifested high OOB error rates (47.3% and 51.1%, respectively) and poor diagnostic abilities (fecal and oral AUC = 0.53). Conclusion: Normal mucosa microbial abundances of adenoma formers manifest unique patterns of microbial diversity that may be predictive of adenoma formation. [ABSTRACT FROM AUTHOR]

Background and Aims To correlate histologic activity in surveillance colonoscopies with the development of colorectal neoplasia in ulcerative colitis [UC]. Methods Colorectal biopsies during surveillance [ N = 764] from 52 UC patients with colorectal neoplasia were compared to 122 patients without neoplasia enrolled in a prospective natural history registry. All biopsies were scored using validated histologic scoring systems (Geboes score, Nancy histopathologic index [NHI], and Robarts histopathologic index [RHI]). Clinical, endoscopic, and histologic data were correlated with the development of colorectal neoplasia. Results In multivariable analysis, mean RHI (hazard ratio [HR] 1.07 for each 1-unit increase in RHI, 95% confidence interval [CI] 1.03–1.12, p = 0.002) and mean NHI [HR 1.89 for each 1-unit increase in NHI, 95% CI 1.34–2.67, p = 0.002] for the entire surveillance period were significantly associated with colorectal neoplasia development. Shorter surveillance interval and increasing age were associated with increased risk of neoplasia development whereas mean Mayo endoscopic score was not significant. To generate a clinically useful measure of neoplasia risk, mean histologic activity in the preceding 5 years before the study endpoint was correlated with neoplasia development. In the preceding 5 years of surveillance, a mean RHI ≥ 8 had a 7.53-fold increased risk [95% CI 2.56–12.16, p < 0.001] and mean NHI ≥ 1.9 had a 5.89-fold increased risk [95% CI 2.18–15.92, p < 0.001] of developing colorectal neoplasia. Conclusions Persistent histologic activity during multiple surveillance episodes is an independent predictor of colorectal neoplasia. Mean RHI and mean NHI during a 5-year colonoscopic surveillance period can be used to assess risk for colorectal neoplasia and optimize UC surveillance. [ABSTRACT FROM AUTHOR]

A substantial body of literature has provided evidence that type 2 diabetes mellitus (T2DM) and colorectal neoplasia share several common factors. Both diseases are among the leading causes of death worldwide and have an increasing incidence. In addition to usual risk factors such as sedentary lifestyle, obesity, and family history, common pathophysiological mechanisms involved in the development of these diseases have been identified. These include changes in glucose metabolism associated with adipose tissue dysfunction including insulin resistance resulting to hyperinsulinemia and chronic hyperglycemia. In addition to altered glucose metabolism, abdominal obesity has been associated with accented carcinogenesis with chronic subclinical inflammation. An increasing number of studies have recently described the role of the gut microbiota in metabolic diseases including T2DM and the development of colorectal cancer (CRC). Due to the interconnectedness of different pathophysiological processes, it is not entirely clear which factor is crucial in the development of carcinogenesis in patients with T2DM. The aim of this work is to review the current knowledge on the pathophysiological mechanisms of colorectal neoplasia development in individuals with T2DM. Here, we review the potential pathophysiological processes involved in the onset and progression of colorectal neoplasia in patients with T2DM. Uncovering common pathophysiological characteristics is essential for understanding the nature of these diseases and may lead to effective treatment and prevention. [ABSTRACT FROM AUTHOR]

High-risk adenomas predict metachronous advanced adenomatous neoplasia. Limited data exist on predictors of metachronous advanced serrated lesions (mASLs). We analyzed clinical and endoscopic predictors of mASLs. In this retrospective cohort study, adults with >1 outpatient colonoscopy between 2008 and 2019 at a tertiary center were included. Serrated lesions (SLs) included sessile SLs (SSLs), traditional serrated adenomas (TSAs), and hyperplastic polyps (HPs). Patient and endoscopic characteristics were obtained using electronic medical records. Five-year cumulative incidence of mASL (HP ≥10 mm, SSL ≥10 mm or with dysplasia, any TSA) and factors associated with mASL were evaluated using Kaplan-Meier estimates and Cox proportional hazards models. A total of 4990 patients were included and 45.4% were women. Mean age was 60.9 ± 9.2 years and median follow-up time was 3.7 years. Female sex and active smoking were associated with mASL. Endoscopically, any SSL and TSA were associated with mASL. The 5-year cumulative incidence for mASL was 26% (95% confidence interval [CI], 18%–32%) for SSL ≥10 mm, 17% (95% CI, 3.5%–29%) for HP ≥10 mm, 21% (95% CI, 0%–42%) for 3–4 SSLs <10 mm, 18% (95% CI, 0%–38%) for TSA, and 27% (95% CI, 3.6%–45%) for SSL with low-grade dysplasia. Baseline synchronous nonadvanced SL and nonadvanced adenoma were not associated with mASL. Our data support current recommendations for a 3-year surveillance interval in patients with baseline SSL ≥10 mm, SSL with dysplasia, and TSA. A 3-year interval may be more appropriate than 3–5 years for patients with baseline HP ≥10 mm or 3–4 SSLs <10 mm. Patients with synchronous nonadvanced SLs and adenomas do not appear to be at increased risk of mASL. [ABSTRACT FROM AUTHOR]

An increasing burden on health care resources has resulted in a backlog of individuals requiring colonoscopy, with delays in surveillance possibly detrimental for individuals at increased risk of colorectal cancer (CRC). This study investigated the use of a 2-sample fecal immunochemical test (FIT) to establish those most likely to have advanced neoplasia (AN) and in need of prioritized surveillance colonoscopy. This was a prospective study conducted in the tertiary care setting. Participants completed a 2-sample FIT (OC-Sensor, Eiken Chemical Company) within 90 days of surveillance colonoscopy. The sensitivity of FIT for detection of AN (CRC or advanced adenoma) in moderate- and high-risk individuals was determined at fecal hemoglobin thresholds between 2 and 80 μg/g feces. A total of 766 patients were included (median age, 66.1 years [interquartile range, 58.1–72.9]; 49.9% male), with AN detected in 8.6% (66/766, including 5 CRC). For moderate-risk individuals (with prior history of adenoma or a significant family history of CRC), sensitivity of FIT for AN ranged from 73.5% at 2 μg/g feces, to 10.2% at 80 μg/g feces. For high-risk conditions (confirmed/suspected genetic syndromes or prior CRC), sensitivity of FIT was similar, ranging from 70.6% at the lowest positivity threshold of 2 μg/g feces, to 11.8% at 80 μg/g feces. Independent variables in the whole cohort for association with detection of AN at surveillance colonoscopy were age (odds ratio, 1.03; 95% confidence interval, 1.00–1.06) and FIT hemoglobin result ≥10 μg/g feces (odds ratio, 1.81; 95% confidence interval, 1.04–3.16). The use of FIT before surveillance colonoscopy provides clinicians with insights into the risk of AN. This raises the possibility of a method to triage individuals, facilitating the more efficient management of endoscopic resources. [ABSTRACT FROM AUTHOR]

In this Clinical Practice Update (CPU), we provide guidance on the appropriate use of different polypectomy techniques. We focus on polyps <2 cm in size that are most commonly encountered by the practicing endoscopist, including use of classification systems to characterize polyps and various polypectomy methods. We review characteristics of polyps that require complex polypectomy techniques and provide guidance on which types of polyps require more advanced management by a therapeutic endoscopist or surgeon. This CPU does not provide a detailed review of complex polypectomy techniques, such as endoscopic submucosal dissection, which should only be performed by endoscopists with advanced training. This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute CPU Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPU Committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. A structured visual assessment using high-definition white light and/or electronic chromoendoscopy and with photodocumentation should be conducted for all polyps found during routine colonoscopy. Closely inspect colorectal polyps for features of submucosally invasive cancer. Use cold snare polypectomy for polyps <10 mm in size. Cold forceps polypectomy can alternatively be used for 1- to 3-mm polyps where cold snare polypectomy is technically difficult. Do not use hot forceps polypectomy. Clinicians should be familiar with various techniques, such as cold and hot snare polypectomy and endoscopic mucosal resection, to ensure effective, safe, and optimal resection of intermediate-size polyps (10–19 mm). Consider using lifting agents or underwater endoscopic mucosal resection for removal of sessile polyps 10–19 mm in size. Serrated polyps should be resected using cold resection techniques. Submucosal injection may be helpful for polyps >10 mm if margins cannot be well delineated. Use hot snare polypectomy to remove pedunculated lesions >10 mm in size. Do not routinely use clips to close resection sites for polyps <20 mm. Refer patients with polyps to endoscopic referral centers in the context of size ≥20 mm, challenging polypectomy location, or recurrent polyp at a prior polypectomy site. Tattoo lesions that may need future localization at endoscopy or surgery. Tattoos should be placed in a location that will not interfere with subsequent attempts at endoscopic resection. Refer patients with nonpedunculated polyps with clear evidence of submucosally invasive cancer for surgical evaluation. Understand the endoscopy suite's electrosurgical generator settings appropriate for polypectomy or postpolypectomy thermal techniques. [ABSTRACT FROM AUTHOR]

In contrast to many observational studies, large-scale randomized trials do not support the protective role of vitamin D for the prevention of colorectal neoplasia. However, in previous studies, individuals with blunted parathyroid hormone (PTH) response to vitamin D insufficiency/deficiency (BPRVID), were not differentiated from those with high PTH response to vitamin D insufficiency/deficiency (HPRVID). Individuals with BPRVID are responsive to magnesium treatment, particularly treatment of magnesium plus vitamin D while those with HPRVID are responsive to vitamin D treatment. We prospectively compared these two distinct groups (i.e. BPRVID and HPRVID) for risk of incident adenoma, metachronous adenoma, and incident colorectal cancer (CRC) Three nested case-control studies in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial. We found optimal 25(OH)D levels were associated with a significantly reduced risk of CRC, primarily among women. The associations between 25(OH)D and CRC risk significantly differed by PTH levels, particularly among women. Compared to individuals with optimal levels for both 25(OH)D and PTH, all others were at an elevated risk of incident CRC, primarily in women. We found those with BPRVID had 2.56-fold significantly increased risk of CRC compared to 1.65-fold non-significantly increased risk for those with HPRVID. Among women, we observed those with BPRVID had 4.79–6.25-fold significantly increased risks of incident CRC and adenoma whereas those with HPRVID had 3.65-fold significantly increased risk of CRC. Individuals with BPRVID are at higher risks of incident adenoma and CRC compared to those with HPRVID, particularly among women. [ABSTRACT FROM AUTHOR]

Background and Aims Ulcerative colitis [UC] patients have a greater risk of developing colorectal cancer through inflammation-dysplasia-carcinoma sequence of transformation. The histopathological diagnosis of dysplasia is therefore of critical clinical relevance, but dysplasia may be difficult to distinguish from inflammatory changes. Methods A proteomic pilot study on five UC colorectal dysplastic patients highlighted proteins differentially distributed between paired dysplastic, inflammatory, and normal tissues. The best candidate marker was selected and immunohistochemistry confirmation was performed on azoxymethane/dextran sulphate sodium [AOM/DSS] mouse model lesions, 37 UC-dysplasias, 14 UC-cancers, 23 cases of long-standing UC, 35 sporadic conventional adenomas, 57 sporadic serrated lesions, and 82 sporadic colorectal cancers. Results Differential proteomics found 11 proteins significantly more abundant in dysplasia compared with inflammation, including Solute carrier family 12 member 2 [SLC12A2] which was confidently identified with eight specific peptides and was below the limit of quantitation in both inflammatory and normal colon. SLC12A2 immunohistochemical analysis confirmed the discrimination of preneoplastic and neoplastic lesions from inflammatory lesions in mice, in UC, and in sporadic contexts. A specific SLC12A2 staining pattern termed 'loss of gradient' reached 89% sensitivity, 95% specificity, and 92% accuracy for UC-dysplasia diagnosis together with an inter-observer agreement of 95.24% [multirater κ free of 0.90; 95% CI: 0.78 - 1.00]. Such discrimination could not be obtained by Ki67 staining. This specific pattern was also associated with sporadic colorectal adenomas and cancers. Conclusions We found a specific SLC12A2 immunohistochemical staining pattern in precancerous and cancerous colonic UC lesions which could be helpful for diagnosing dysplasia and cancer in UC and non-UC patients. [ABSTRACT FROM AUTHOR]

Recently, technological advances through endoscopic submucosal dissection, per oral endoscopic myotomy, and submucosal tunnel endoscopic resection allowed the extension of therapeutic endoscopy from treatment of luminal to extraluminal neoplasia. The performance of endoscopic full thickness resection (EFTR) allowed en bloc resection of luminal and extraluminal neoplasia with adequate resection margins. EFTR is currently indicated for treatment of gastrointestinal stromal tumors, early GI neoplasia with nonlifting or recurrent adenoma or neoplasia after endoscopic resection. This chapter reviews the devices and technologies used for EFTR, the clinical results reported in the literature as well as possible future developments for EFTR. [ABSTRACT FROM AUTHOR]

Background The immunochemical fecal occult blood test (iFOBT) is an alternative method to colonoscopy that can be used for colorectal cancer (CRC) screening. If the iFOBT result is positive, a colonoscopy is recommended. In this retrospective study, we identify factors associated with negative colonoscopy and positive iFOBT results obtained during CRC screening. Methods We collected data for subjects who received a colonoscopy at Taipei Veterans General Hospital after receiving a positive iFOBT result during CRC screening from January 2015 to December 2015. Subjects' baseline data, medications, and co-morbidities as well as colonoscopy and histological findings were recorded. A negative colonoscopy result was defined as no detection of any colorectal neoplasia including non-advanced adenoma, advanced adenoma, and adenocarciona. Multivariate logistic regression analysis was conducted to identify the associated factors in screening subjects with positive iFOBT but negative colonoscopy results. Results 559 (46.3%) out of 1207 eligible study subjects received a colonoscopy with a negative result. Multivariate logistic regression analysis revealed that the use of antiplatelets [odds ratio (OR) = 0.654; 95% confidence interval (CI), 0.434–0.986], occurrence of hemorrhoid (OR = 0.595; 95% CI, 0.460–0.768), and the existence of colitis/ulcer (OR = 0.358; 95% CI, 0.162–0.789) were independent factors associated with negative colonoscopy but positive iFOBT results during CRC screening. The colon clean level, underlying diseases of gastrointestinal bleeding tendency (e.g., chronic kidney disease, cirrhosis), and the use of anticoagulant or nonsteroidal anti-inflammatory agents were not associated with negative colonoscopy and positive iFOBT results. Conclusion The use of antiplatelet agents and the presence of hemorrhoids and colitis/ulcers were factors associated with negative colonoscopy and positive iFOBT results. [ABSTRACT FROM AUTHOR]

Background and Aims: The association between thiopurines and colorectal neoplasia risk remains controversial in inflammatory bowel disease [IBD] patients. We performed a systematic review and meta-analysis examining this association. Methods: A comprehensive search of the PubMed, EMBASE and Cochrane Library databases was performed to identify relevant literature. Random-effects models were applied to calculate the pooled odds ratio [OR] and relative risk [RR] with corresponding 95% confidence intervals [CIs] among case-control and cohort studies. Results: Eleven cohort and 16 case-control studies involving 95 397 patients were included in this study. Overall, the use of thiopurines was associated with a reduced risk of colorectal neoplasia both in case-control [OR = 0.49, 95% CI: 0.34-0.70] and cohort studies [RR = 0.96, 95% CI: 0.94-0.98]. Moreover, a protective effect of thiopurines against advanced neoplasia [high-grade dysplasia and cancer] [OR = 0.51, 95% CI: 0.31-0.84 for case-control studies; RR = 0.96, 95% CI: 0.94-0.98 for cohort studies] and colorectal cancer [CRC] [OR = 0.56, 95% CI: 0.34-0.93 for case-control studies; RR = 0.96, 95% CI: 0.94-0.98 for cohort studies] was also observed. Furthermore, when the analysis was conducted on patients at a high risk for colorectal neoplasia, the chemopreventive effect was confirmed in patients with long disease duration [> 8 years] but not in those with extensive colitis or primary sclerosing cholangitis. Conclusions: This study demonstrated that thiopurine use was associated with a reduced risk of colorectal neoplasia, advanced neoplasia and CRC in IBD patients, especially those with long disease duration [> 8 years]. [ABSTRACT FROM AUTHOR]

In above-average-risk individuals undergoing colonoscopy-based surveillance for colorectal cancer (CRC), screening with fecal immunochemical tests (FIT) between colonoscopies might facilitate personalization of surveillance intervals. Because a negative FIT is associated with a reduced risk for CRC, we examined the relationship between number of rounds of negative FIT and risk for advanced neoplasia in individuals undergoing surveillance colonoscopy. We conducted a retrospective cohort study on 4021 surveillance intervals in 3369 individuals (50–74 years), who had completed a 2-sample FIT between colonoscopies, from 1 to 4 rounds at 1–2 yearly intervals, each with a negative result (<20 μg hemoglobin/g feces). Incidence of advanced neoplasia (CRC or advanced adenoma) was determined at the follow-up colonoscopy. Competing-risk regression was used to assess the association between multiple negative FIT results and the risk of advanced neoplasia within 2 years. The incidence of advanced neoplasia in the cohort was 9.9% and decreased with increasing numbers of rounds of negative FIT results: 11.1% after 1 negative FIT to 5.7% after 4 negative FIT. The risk of advanced neoplasia was significantly lower in participants with 3 (subdistribution hazard ratio, 0.50; 95% confidence interval, 0.24–0.97) and 4 (subdistribution hazard ratio, 0.33; 95% confidence interval, 0.15–0.73) rounds of negative FIT compared with only 1 negative FIT. There was a low risk of advanced neoplasia after multiple rounds of negative FIT in above-average-risk people undergoing surveillance with no neoplasia or nonadvanced adenoma at prior colonoscopy. This supports the use of interval FIT to personalize surveillance by lengthening colonoscopy intervals following multiple negative FIT results. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Family history of cancers at different sites except for colorectum has not been evaluated as a risk factor for colorectal neoplasia (CRN). Aims To investigate CRN risk according to family history of cancers at 12 different sites, including stomach and colorectum. Methods A cross-sectional study was performed on 139,497 asymptomatic Koreans who underwent colonoscopy as part of a health check-up. Results The mean age of the study population was 41.6 and the prevalence of CRN was 16.3%. Multivariate analyses revealed that family histories of CRC (adjusted odds ratio; confidence interval, 1.26; 1.17–1.35) and gastric cancer (1.07; 1.01–1.13) were independent risk factors for CRN. Notably, the risk of CRN increased even more for participants with family histories of both CRC and gastric cancer (1.38; 1.12–1.70). Family history of CRC was associated with risk of CRN in participants aged both <50 and ≥50 years, whereas family history of gastric cancer was associated with risk of CRN in participants aged <50 years (1.22; 1.14–1.30), but not in participants aged ≥50 years (1.08; 0.99–1.18). Conclusions Family history of gastric cancer was an independent risk factor for CRN, especially in those aged <50 years. Persons with family histories of gastric cancer and CRC, especially those with family histories of both, may need to begin colonoscopy earlier. [ABSTRACT FROM AUTHOR]

Purpose: Limited data are available regarding the association between circulating serum carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9 (CA 19-9) concentrations and colorectal adenoma. We aimed to investigate whether elevated serum CEA and CA 19-9 levels are correlated with the presence of colorectal neoplasia (CRN) and whether the levels of these antigens vary according to CRN severity. Materials and Methods: A cross-sectional study was performed on asymptomatic subjects who underwent colonoscopy between 2010 and 2014 as part of a comprehensive health screening program in Korea. Results: A total of 124509 participants with measured serum CEA levels and 115833 participants with measured serum CA 19-9 levels were analyzed. Elevated CEA concentrations were associated with a higher rate of any adenoma, advanced adenoma, high-risk adenoma, advanced CRN (ACRN), overall CRN, and colorectal cancer (CRC). Elevated CA 19-9 concentrations were also associated with a higher rate of advanced adenoma, high-risk adenoma, ACRN, and CRC. Both elevated levels of CEA and CA 19-9 were identified as independent predictors of ACRN. Among patients with CRN, the proportions of elevated CEA/CA 19-9 levels were significantly higher in patients with ACRN than in those with non-ACRN, and these levels were correlated with larger lesion size and multiplicity of adenomas. Conclusion: Both elevated serum CEA and CA 19-9 levels were associated with the presence of ACRN, as well as CRC. Elevated CEA levels were also associated with the presence of overall CRN. Moreover, both CEA and CA 19-9 levels were correlated with the severity of CRN. [ABSTRACT FROM AUTHOR]

Objective The incidence of colorectal cancer is increasing, mainly due to the aging of the population. Frailty, describing a state of increased vulnerability, is common in older patients, but frailty and high age are not necessarily contraindications to surgical treatment. However, limited data describing long-term outcomes after surgery in this patient group exist. In this clinical follow-up study, we aimed to examine long-term health-related quality of life in older surgical patients with colorectal cancer. Materials and Methods Patients were recruited from a prospective multicenter study investigating frailty as a predictor of postoperative complications after surgery for colorectal cancer. A preoperative geriatric assessment was performed, and patients were classified as frail or non-frail. Patients responded to version 3.0 of The European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire-C30 before surgery, 3 months postoperatively and at a long-term follow-up 16–28 months (median 22 months) after surgery. One-way repeated-measures analyses of variance were performed to examine changes in scores over time. Results 180 patients with a mean age of 80 years were included at baseline, 138 at 3 months postoperatively, and 84 patients (69% of survivors) at long-term follow-up. A significant improvement in quality of life-scores was present 3 months after surgery, also in the subgroup of frail patients. At long-term follow-up, scores decreased, but to values above baseline. Conclusion Health-related quality of life may be improved in older patients after surgery for colorectal cancer, even in patients who are classified as frail preoperatively. [ABSTRACT FROM AUTHOR]

To determine the long-term outcomes after colorectal endoscopic submucosal dissection (ESD), we conducted a large, multicenter, prospective cohort trial with a 5-year observation period. Between February 2013 and January 2015, we consecutively enrolled 1740 patients with 1814 colorectal epithelial neoplasms ≥20 mm who underwent ESD. Patients with noncurative resection (non-CR) lesions underwent additional radical surgery, as needed. After the initial treatment, intensive 5-year follow-up with planned multiple colonoscopies was conducted to identify metastatic and/or local recurrences. Primary outcomes were overall survival, disease-specific survival, and intestinal preservation rates. The rates of local recurrence and metachronous invasive cancer were evaluated as the secondary outcomes. The 5-year overall survival, disease-specific survival, and intestinal preservation rates were 93.6%, 99.6%, and 88.6%, respectively. Patients with CR lesions had no metastatic occurrence, and patients with non-CR lesions had 4 metastatic occurrences. Kaplan–Meier curves revealed that overall survival and disease-specific survival rates were significantly higher in patients with CR lesions than in those with non-CR lesions (P >.001 and P =.009, respectively). Local recurrence occurred in only 8 lesions (0.5%), which were successfully resected by subsequent endoscopic treatment. Multiple logistic regression analyses revealed that piecemeal resection (hazard ratio, 8.19; 95% CI, 1.47–45.7; P =.02) and margin-positive resection (hazard ratio, 8.06; 95% CI, 1.76–37.0; P =.007) were significant independent predictors of local recurrence after colorectal ESD. Fifteen metachronous invasive cancers (1.0%) were identified during surveillance colonoscopy, most of which required surgical resection. A favorable long-term prognosis indicates that ESD can be the standard treatment for large colorectal epithelial neoplasms. Clinical Trial Registration Number: UMIN000010136. [Display omitted] Accurate histologic assessment facilitated by endoscopic submucosal dissection enables stratification of the risk of lymph node metastasis and determines the necessity of additional surgery, which may have led to a good long-term prognosis. [ABSTRACT FROM AUTHOR]

Abstract: Background: Since there are few prospective studies on colorectal endoscopic resection to date, we aimed to prospectively assess safety and efficacy of endoscopic resection in a cohort of Italian patients. Methods: Prospective multicentre assessment of resection of sessile polyps or non-polypoid lesions≥10mm in size or smaller (if depressed). Outcome measures included complete excision, morbidity, mortality, and residual/recurrence at 12 months. Results: Overall, 1012 resections in 928 patients were analysed (62.4% sessile polyps, 28.8% laterally spreading tumours, 8.7% depressed non-polypoid lesions). Lesions were prevalent in the proximal colon. Enbloc resection was possible in 715/1012 cases (70.7%), whereas piecemeal resection was required in 297 (29.3%). Endoscopically complete excision was achieved in 866 cases (85.6%). Adverse events occurred in 83 (8.2%), and no deaths occurred. Independent predictors of 12-month residual/recurrence were the location of the lesion in the proximal colon (OR 2.22 [95% CI 1.16–4.26]; p =0.015) and piecemeal endoscopic resection (OR 2.76 [95% CI 1.56–4.87]; p =0.0005). Limitations of the study were: potential expertise bias, no data on eligible and potentially resectable excluded lesions, high percentage of lesions<20mm, follow-up limited to 1 year. Conclusion: In this registry study the endoscopic resection of colorectal lesions was safe and achieved high rates of long-term endoscopic clearance. [Copyright &y& Elsevier]

Abstract: Aims: Colorectal cancer (CRC) sheds viable cells in the mucocelluar layer overlaying the colonic mucosa which travels distally alongside the faecal stream. These cells can be retrieved from the surface of the rectal mucosa. DNA quantification of these cells may be a marker of CRC, assessment of which was aim of this study. Methods: A prospective double-blinded study of 467 consecutive patients referred with symptoms suggestive of CRC. Cells were collected from the surface of the rectal mucosa and total DNA quantified. DNA scores were compared with outcome after subjects had completed bowel investigations. Analysis of receiver operating characteristic (ROC) curves was performed to determine the optimum cut-off point for a positive result. Results: 107 of the 467 patients were excluded due to; excessive faecal contamination of samples (n = 84); declined investigations (n = 17); inappropriate referral (n = 5); unfit (n = 1). 263 patients had lower GI endoscopy; 89 CT colonography and 8 barium enema. The diagnosis were; CRC (n = 23), inflammatory bowel disease (IBD) (n = 7), adenomatous polyps (AP) (n = 20) and no significant abnormality detected (n = 310). ROC analysis revealed that sensitivities at a specificity of 60% for detecting CRC were 91.3%; for CRC and IBD 86.7%; and for CRC, IBD and AP 72.0%. Conclusion: In symptomatic patients DNA quantification of cells retrieved from the surface of the rectal mucosa is sensitive for the detection of CRC. Although faecal contamination is a limitation of this technique, refinement and application of other molecular tests hold promise for a better non invasive method for the detection of CRC. [Copyright &y& Elsevier]

Abstract: Background: Suboptimal colonoscopy quality is related to a higher risk of interval cancer. Aim of our study was to explore the variability in detection rate of neoplasia among different endoscopic centres in an unselected population. Methods: Consecutive patients referred for colonoscopy in 28 Italian centres were included. Detection rate for polyp, neoplasia and advanced neoplasia was assessed at both the individual and centre level. Inter-centre variability in detection rate of colorectal lesions was explored after adjusting for patient-related factors at multivariate analysis. Results: 3150 patients were included. Median detection rates for polyp, neoplasia and advanced neoplasia were 35%, 26% and 13%. At multivariate analysis, patient-related factors associated with neoplasia detection were age, sex, alcohol and smoking history. After adjusting for these variables, a statistically significant difference in the observed/expected ratio among different centres was observed (Chi-squared test: p <0.01). Among non-patient-related factors, documentation of withdrawal time was associated with neoplasia detection. However, a statistically significant inter-centre variability also remained after adjusting for this variable. Conclusions: A wide variability was present in the detection rate of neoplasia and advanced neoplasia at the level of endoscopic centres in an unselected population. The adoption of a centre-related neoplasia detection rate could be suggested as a performance indicator. [Copyright &y& Elsevier]

Patients with advanced colorectal adenomas (AAs) are directed to undergo intensive surveillance. However, the benefit derived from surveillance may be outweighed by the risk of death from non-colorectal cancer (CRC) causes, leading to uncertainty on how best to individualize follow-up. The aim of this study was to derive a risk prediction model and risk index that estimate and stratify the risk for non-CRC cancer mortality (NCM) subsequent to diagnosis and removal of AA. We conducted a retrospective cohort study of veterans ≥40 years old who had colonoscopy for diagnostic or screening indications at 13 Veterans Affairs Medical Centers between 2002 and 2009 and had 1 or more AAs. The primary outcome was NCM using a fixed follow-up time period of 5 years. Logistic regression using the lasso technique was used to identify factors independently associated with NCM, and an index based on points from regression coefficients was constructed to estimate risk of 5-year NCM. We identified 2943 veterans with AA (mean age [standard deviation] 63 [8.6] years, 98% male, 74% white), with an overall 5-year mortality of 16.7%, which was nearly all due to NCM (16.6%). Age, comorbidity burden, specific comorbid conditions, and hospitalization within the preceding year were independently associated with NCM. The risk prediction model had a goodness of fit (calibration) P value of.41 and c-statistic (discrimination) of 0.74 (95% confidence interval, 0.71–0.76). On the basis of comparable 5-year risks of NCM, the scores comprised 3 risk categories: low (score of 0–1), intermediate (score of 2–4), and high (score of ≥5), in which NCM occurred in 6.5%, 14.1%, and 33.2%, respectively. We derived a risk prediction model that identifies veterans with advanced adenomas who are at high risk of NCM within 5 years, and who are thus unlikely to benefit from further surveillance. [ABSTRACT FROM AUTHOR]

Patients with inflammatory bowel disease are at increased risk of colorectal neoplasia (CRN) due to mucosal inflammation. As current surveillance guidelines form a burden on patients and healthcare costs, stratification of high-risk patients is crucial. Cigarette smoke reduces inflammation in ulcerative colitis (UC) but not Crohn's disease (CD) and forms a known risk factor for CRN in the general population. Due to this divergent association, the effect of smoking on CRN in IBD is unclear and subject of this study. In this retrospective cohort study, 1,386 IBD patients with previous biopsies analyzed and reported in the PALGA register were screened for development of CRN. Clinical factors and cigarette smoke were evaluated. Patients were stratified for guideline-based risk of CRN. Cox-regression modeling was used to estimate the effect of cigarette smoke and its additive effect within the current risk stratification for prediction of CRN. 153 (11.5%) patients developed CRN. Previously described risk factors, i.e. first-degree family member with CRN in CD (p-value=.001), presence of post-inflammatory polyps in UC (p-value=.005), were replicated. Former smoking increased risk of CRN in UC (HR 1.73; 1.05-2.85), whereas passive smoke exposure yielded no effect. For CD, active smoking (2.20; 1.02–4.76) and passive smoke exposure (1.87; 1.09-3.20) significantly increased CRN risk. Addition of smoke exposure to the current risk-stratification model significantly improved model fit for CD. This study is the first to describe the important role of cigarette smoke in CRN development in IBD patients. Adding this risk factor improves the current risk stratification for CRN surveillance strategies. [ABSTRACT FROM AUTHOR]

Abstract: Background and aim: Longstanding ulcerative colitis (UC) predisposes to colorectal cancer (CRC). To understand the molecular pathogenesis of colitis-associated colorectal neoplasia (UC-CRN), we studied the frequency of microsatellite instability (MSI) and mutations in p53, BRAF and KRAS genes in the tissues of patients with long standing UC with or without neoplasia and compared them with colitis patients without risk of neoplasia, and those with sporadic colorectal neoplasia (S-CRN) in an area with lower prevalence for either disease. Methods: Biopsies were obtained during magnifying chromo colonoscopy or routine colonoscopy in consecutive UC patients with high risk (UC-HR) and low risk (UC-LR) of neoplasia, and those with S-CRN. MSI (NCI-Bethesda panel) and mutations in p53, KRAS and BRAF genes were analysed. Results: Twenty-eight patients with UC-HR, 30 with UC-LR and 30 with S-CRN were included. Six (21.4%) of UC-HR had neoplasia (Progressors). MSI was not detected in the UC-CRN group as compared to 5 (16.7%) in the S-CRN group. p53 mutations occurred in 1 (3.3%) of UC-LR, increasing to 6 (27.3%, P <0.05) and 3 (50%, P <0.05) in the UC-HR subgroups without and with neoplasia respectively, as against 10 (33.3%) in sporadic neoplasia group. KRAS mutations were found only in the presence of neoplasia. None showed the BRAF mutation. Conclusions: In a population with a lower prevalence for UC and CRC, the molecular pathogenesis of colitis-associated colorectal neoplasia is comparable to that reported from areas with a higher prevalence of these diseases, MSI being an exception. [Copyright &y& Elsevier]

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are naturally occurring omega (ω)-3 long-chain polyunsaturated fatty acids (PUFAs), which are found in highest quantities in oily fish such as sardines and mackerel. Epidemiological studies of the association between fish intake, ω-3 PUFA intake or blood ω-3 PUFA levels and colorectal cancer (CRC) risk have not consistently suggested beneficial effects of ω-3 PUFAs on CRC (and other gastrointestinal cancer) risk. However, dietary administration of one or both of the main ω-3 PUFAs in rodent models of colorectal carcinogenesis has been demonstrated to reduce colorectal tumour size and multiplicity, compatible with CRC chemopreventative activity. EPA has now been demonstrated to reduce rectal polyp number and size in patients with familial adenomatous polyposis. A randomized polyp prevention trial of EPA is underway in order to test chemopreventative efficacy against ‘sporadic’ colorectal neoplasia. [Copyright &y& Elsevier]

Background & Aims: Adenoma detection rates might be improved through use of high-definition colonoscopy, which can detect subtle mucosal changes. We investigated whether the use of high-definition white-light (HDWL) colonoscopy resulted in a higher rate of adenoma detection than standard-definition white-light (SDWL) colonoscopy in a clinical practice setting. Methods: This retrospective study included 2430 patients who underwent colonoscopies from September 2006 to December 2007; 1226 received SDWL colonoscopy and 1204 received HDWL colonoscopy. We analyzed data from consecutive screening, surveillance, and diagnostic colonoscopies, comparing adenoma and overall polyp detection between procedures. Potentially confounding variables were controlled using multivariable logistic regression analysis. Results: The adenoma detection rate was higher among patients who underwent HDWL compared with SDWL colonoscopies (28.8% vs 24.3%; P = .012), as was the polyp detection rate (42.2% vs 37.8%; P = .026). These findings remained after adjustments for potentially confounding variables (P = .018 and .022, respectively). Conclusions: In a general clinical practice setting, HDWL colonoscopy resulted in a higher adenoma detection rate compared with SDWL colonoscopy. The use of SDWL colonoscopy could reduce the number of missed adenomas and the subsequent risk for colorectal cancer. [Copyright &y& Elsevier]

Background & Aims: Probe-based confocal laser endomicroscopy (pCLE) allows in vivo imaging of tissue at micron resolution. Virtual chromoendoscopy systems, such as Fujinon intelligent color enhancement and narrow band imaging, also have potential to differentiate neoplastic colorectal lesions. The accuracy of these systems in clinical practice is, however, unknown. Our primary aim was to compare sensitivity and specificity of pCLE to virtual chromoendoscopy for classification of colorectal polyps using histopathology as a gold standard. A secondary aim was to compare sensitivity and specificity of pCLE to virtual chromoendoscopy using a modified gold standard that assumed that all polyps ≥10 mm had malignant potential and were considered neoplastic or high risk. Methods: Patients underwent colonoscopy using high-resolution colonoscopes. The surface pit pattern was determined with NBI or FICE in all patients. Confocal images were recorded and subsequently analyzed offline, blinded to the endoscopic characteristics and histopathology. Each polyp was diagnosed as benign or neoplastic based on confocal features according to modified Mainz criteria. Results: A total of 119 polyps (81 neoplastic, 38 hyperplastic) from 75 patients was assessed. The pCLE had higher sensitivity compared to virtual chromoendoscopy when considering histopathology as gold standard (91% vs 77%; P = .010) and modified gold standard (88% vs 76%; P = .037). There was no statistically significant difference in specificity between pCLE and virtual chromoendoscopy when considering histopathology or modified gold standard. Conclusions: Confocal endomicroscopy demonstrated higher sensitivity with similar specificity in classification of colorectal polyps. These new methods may replace the need for ex vivo histological confirmation of small polyps, but further studies are warranted. [Copyright &y& Elsevier]

Summary: The aim of this study is to evaluate the methylation status of normal colonic mucosa in relation to the stage of neoplasia arising from the mucosa. The methylation status of 2 age-related loci (ESR1 and MYOD1) and global methylation (the mean of Alu and Sat2) in the normal colonic mucosa of 156 patients with and without colorectal neoplasia were examined. The distal colon and proximal colon were analyzed separately because neoplasia is biologically and clinically different between these sites. The methylation status was determined by MethyLight using percentage of methylated reference (PMR). In the distal colon, methylation of the age-related loci decreased as the stage of neoplasia increased (patients with no neoplasia or with adenoma ≤9 mm versus patients with advanced adenoma or with invasive cancer: ESR1-PMR median, 21.0 versus 15.7; P = .015; MYOD1-PMR median, 5.35 versus 3.80; P = .0037, respectively). Interestingly, global methylation was inversely correlated with the stage of neoplasia (59.7 versus 61.5; P = .054). In contrast, the proximal colon showed no significant correlations. The methylation of MYOD1 in the normal mucosa was significantly correlated with K-ras mutation in neoplastic tissue arising from the mucosa. Specific epigenetic changes in normal colonic mucosa may be correlated with the occurrence and development of neoplasia in the distal colon. [Copyright &y& Elsevier]

Abstract: The impressive and brisk evolution of medical science prevents many physicians from a thorough update on all the research fields. Colorectal cancer diagnosis, screening and follow-up is well known to require a multi-disciplinary approach, as it is faced by several specialties such as primary care physicians, gastroenterologists, non-gastroenterologist internists, radiologists and surgeons. To address this issue in a mutual perspective, we focused on the main points of the epidemiology, diagnosis, screening and follow-up of colorectal neoplasia by using a simple “Question & Answers” structure. [Copyright &y& Elsevier]

Summary: This study examines the expression of the insulin-like growth factor type 1 receptor (IGF-1R) in colorectal neoplasia. Previous studies have shown that the IGF-1R is expressed at high levels in normal embryonic stem cells and in many cancer phenotypes. However, lower IGF-1R levels are expressed in some advanced cancer phenotypes. The timing of and the reasons for these changes in expression during the evolution of a cancer are not understood. Here, we examine IGF-1R expression in the evolution of colorectal cancer by means of Northern blotting and immunohistochemistry validated by tissue and reagent controls and Western blotting. We show for the first time that (1) in normal colorectal crypts, epithelial stem cells in the basal crypt region express high IGF-1R levels, which decrease to low levels when these cells migrate to and differentiate in the mid and upper crypt regions; (2) in tumor initiation in aberrant crypt foci, all of the transformed cells express high levels of the IGF-1R at stem cell levels throughout the crypt axis; (3) in tumor progression in adenomatous and cancerous crypts, tumor cells of an epithelial type morphology express high levels of the IGF-1R; (4) in advanced cancers, low levels of the IGF-1R are expressed in invasive foci where cancer cells dedifferentiate to a mesenchymal-type morphology and show a loss of cell adhesion. Interestingly, these cells can form an alternating pattern with mesenchymal type cells that show cell adhesion and high levels of IGF-1R expression. In summary, this study shows that high-level IGF-1R expression in colorectal neoplasia is initiated by an abnormality of stem cell programed differentiation in the aberrant crypt focus. However, low-level IGF-1R expression is found in some invasive cancers where it is consequent to cancer cell dedifferentiation to a mesenchymal type morphology with loss of cell adhesion. [Copyright &y& Elsevier]

PURPOSE: Dietary fiber has been implicated in colorectal neoplasia, despite conflicting evidence. This is a review of the currently available data on the role of dietary fiber in colorectal carcinogenesis. METHODS: A literature search was conducted using the MEDLINE database. All case-control, longitudinal, and randomized, controlled studies published in English between 1988 and 2000 were identified, as were animal model studies in the period 1986 to 2000. Data from the various studies were tabulated and systematically analyzed, with particular emphasis on the effect of dietary fiber on tumor incidence and luminal parameters such as short chain fatty acids. RESULTS: Epidemiologic correlation studies show a high intake of dietary fiber to be associated with a lower risk of colorectal neoplasia. Thirteen of the 24 case-control studies reviewed demonstrated a protective effect of dietary fiber against colorectal neoplasia, and 16 showed a protective effect of vegetables or vegetable fiber. On the other hand, of 13 longitudinal studies in various cohorts, only 3 demonstrated a protective effect of fiber and 4 a protective effect of vegetables or vegetable fiber. The five published randomized, controlled trials all investigated the effect of increased fiber intake on short-term adenoma recurrence; however, none showed any significant protective effect. Among 19 experimental studies in animal models, 15 showed a protective effect of fiber against tumor induction compared with controls. Animal studies also showed that poorly fermentable fibers (e.g., wheat bran and cellulose) were more protective than soluble fibers (e.g., guar gum and oat bran), which sometimes enhanced carcinogenesis. No clear correlation was found between luminal pH or short chain fatty acids and tumor induction. CONCLUSIONS: On the basis of current data, there is little evidence to support the use of dietary fiber supplements to reduce the risk of colorectal neoplasia. Lifelong and early exposure may be important but are difficult to study. Other risk factors interact with the effects of dietary fiber. [ABSTRACT FROM AUTHOR]

Background & Aims The fecal immunochemical test (FIT) is the tool most frequently used for colorectal cancer (CRC) screening worldwide. It is unclear how the use of aspirin and oral anticoagulants in the screening population affects the diagnostic performance of FIT. Methods We performed a cross-sectional study in an ongoing CRC screening trial in Norway. Participants aged 50–74 years with a positive result from an FIT (>15 μg hemoglobin/g feces) and subsequent colonoscopy (reference standard) were included. Those who used regular aspirin, warfarin, or direct-acting oral anticoagulants (DOACs) were defined as users. Non-users were matched according to age, sex, screening center, and screening round. The primary outcomes were the positive predictive value (PPV) for CRC and advanced adenoma. Results Among 4908 eligible participants, 1008 used aspirin, 147 used warfarin, 212 used DOACs, and 3541 were non-users. CRCs were found in 234 individuals and advanced adenomas in 1305 individuals. The PPV for CRC was 3.8% for aspirin users vs 6.4% for matched non-users (P =.006), The PPV for advanced adenoma in aspirin users was 27.2% vs 32.6% for matched non-users (P =.011). For DOAC, the PPV for CRC was 0.9% in users vs 6.8% in matched non-users (P =.001). The PPV for advanced adenoma in DOAC users was 20.5% vs 32.4% in matched non-users (P =.002). There was no significant difference in PPV for CRC or advanced adenoma in warfarin users compared to non-users. Conclusions In a large screening cohort in Norway, regular use of aspirin and particularly DOACs, were associated with lower PPV of FIT for detection of CRCs and advanced adenomas. ClinicalTrials.gov ID NCT01538550. Graphical abstract [ABSTRACT FROM AUTHOR]

The increasing incidence of colorectal cancer in younger adults (aged <50 years) has been widely reported. Using data from the Surveillance, Epidemiology, and End Results Program, we found young-onset colorectal cancer incidence rates decreased from 1975 through about 1990. Decreases were more prominent in the colon, a contrast with more recent increases in rectal cancer. Incidence rates subsequently increased, differing by time period and 5-year age group. This inflection point is consistent with a birth cohort effect and points to early life exposures—accumulated throughout the life course—that may increase cancer risk. Studying early life exposures among persons born after 1960 may advance our understanding of colorectal cancer in younger adults. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: The association of celiac disease with colorectal neoplasia is controversial. The aim of this study was to determine the risk of colorectal neoplasia among patients with celiac disease. Methods: We carried out a multicenter, retrospective case–control study, within four community hospitals. Celiac disease patients with a complete colonoscopy were regarded as cases and those without celiac disease as controls. For each case, two controls matched for age, sex, indication for colonoscopy and colorectal cancer family history, were randomly selected. The main outcome evaluated was risk of colorectal polyps, adenomas, advanced neoplastic lesions and cancer. Results: We identified 118 patients with celiac disease and 236 controls. The risk of polyps, adenomas and advanced neoplastic lesions was similar in both groups (OR 1.25, CI 0.71–2.18, p=0.40; OR 1.39, CI 0.73–2.63, p=0.31; and OR 1.00, CI 0.26–3.72, p=1.00, respectively). On multivariate analysis, age >75years old, and first-grade CRC family history were associated with adenomas (OR 2.68 CI 1.03–6.98, OR 6.68 CI 1.03–47.98 respectively) and advanced neoplastic lesions (OR 15.03, CI 2.88–78.3; OR 6.46 CI 1.23–33.79, respectively). With respect to celiac disease characteristic, a low adherence to a gluten free diet was independently associated with the presence of adenomas (OR 6.78 CI 1.39–33.20 p=0.01). Conclusions: Celiac disease was not associated with an increased risk of colorectal neoplasia. Nonadherence to a strict gluten free diet was associated with the presence of adenomas. Further studies addressing celiac disease characteristics are needed to confirm this observation. [Copyright &y& Elsevier]

Background & Aims: Two European randomized trials (N = 30,000) compared guaiac fecal occult blood testing with quantitative fecal immunochemical testing (FIT) and showed better attendance rates and test characteristics for FIT. We aimed to identify the most cost-effective FIT cutoff level for referral to colonoscopy based on data from these trials and allowing for differences in screening ages. Methods: We used the validated MIcrosimulation SCreening ANalysis (MISCAN)-Colon microsimulation model to estimate costs and effects of different screening strategies for FIT cutoff levels of 50, 75, 100, 150, and 200 ng/mL hemoglobin. For each cutoff level, screening strategies were assessed with various age ranges and screening intervals. We assumed sufficient colonoscopy capacity for all strategies. Results: At all cost levels, FIT screening was most effective with the 50 ng/mL cutoff level. The incremental cost-effectiveness ratio of biennial screening between ages 55 and 75 years using FIT at 50 ng/mL, for example, was 3900 euro per life year gained. Annual screening had an incremental cost-effectiveness ratio of 14,900 euro per life year gained, in combination with a wider age range (between ages 45 and 80 years). In the sensitivity analysis, 50 ng/mL remained the preferred cutoff level. Conclusions: FIT screening is more cost-effective at a cutoff level of 50 ng/mL than at higher cutoff levels. This supports the recommendation to use FIT at a cutoff level of 50 ng/mL, which is considerably lower than the values used in current practice. [ABSTRACT FROM AUTHOR]

Background & Aims: Successful colonoscopies require good bowel preparations—poor bowel preparations can increase medical costs, rates of missed lesions, and procedure duration. The combination of polyethylene glycol (PEG) 3350 without electrolytes (MiraLAX; Schering-Plough Healthcare Products, Inc, Kenilworth, NJ) and 64 oz of Gatorade (PepsiCo, Inc, Purchase, NY) has gained popularity as a bowel preparation regimen. However, the efficacy and tolerability of this approach has not been compared with standard bowel preparations in clinical trials. We compared split-dose (PEG) 3350 with electrolytes (GoLytely; Braintree Laboratories, Inc, Braintree, MA) with split-dose MiraLAX alone and in combination with pretreatment medications (bisacodyl or lubiprostone) to determine the efficacy and patient tolerability of MiraLAX as an agent for bowel preparation. Methods: We performed a prospective, randomized, blinded, controlled trial at a tertiary care center. Patients (n = 403) were randomly assigned to groups given GoLytely, MiraLAX, MiraLAX with bisacodyl (10 mg), or MiraLAX with lubiprostone (24 μg). MiraLAX was combined with 64 oz of Gatorade. All patients were surveyed regarding preparation satisfaction and tolerability. The Ottawa bowel preparation scale was used to grade colon cleanliness. Results: GoLytely was more effective at bowel cleansing (average Ottawa score, 5.1) than MiraLAX alone (average Ottawa score, 6.9) or in combination with lubiprostone (average Ottawa score, 6.8), or bisacodyl (average Ottawa score, 6.3) (P < .001). MiraLAX was associated with a trend toward longer procedure duration (P = .096). Groups given MiraLAX rated the overall experience as more satisfactory than those given GoLytely (P < .001). There were no differences between polyp detection rates (P = .346) or adverse events (P = .823). Conclusions: Split-dose MiraLAX in 64 oz of Gatorade is not as effective as 4 L split-dose GoLytely in bowel cleansing for screening colonoscopies. [Copyright &y& Elsevier]

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