Distal Adenomas Research Articles

The impact of endoscopist performance and patient factors on distal adenoma detection and colorectal cancer incidence

BackgroundHigh quality endoscopy is key for detecting and removing precursor lesions to colorectal cancer (CRC). Adenoma detection rates (ADRs) measure endoscopist performance. Improving other components of examinations could increase adenoma detection.AimsTo investigate how endoscopist performance at flexible sigmoidoscopy (FS) affects adenoma detection and CRC incidence.MethodsAmong 34,139 participants receiving FS screening by the main endoscopist at one of 13 centres in the UK FS Screening Trial, median follow-up was 17 years. Factors examined included family history of CRC, bowel preparation quality, insertion and withdrawal time, bowel segment reached, patient pain and ADR. Odds ratios (OR) for distal adenoma detection were estimated by logistic regression. Hazard ratios (HR) for distal CRC incidence were estimated by Cox regression.ResultsAt screening, 4,104 participants had distal adenomas detected and 168 participants developed distal CRC during follow-up. In multivariable models, a family history of CRC (yes vs. no: OR 1.40, 95%CI 1.21–1.62), good or adequate bowel preparation quality (vs. excellent: OR 0.84, 95%CI 0.74–0.95; OR 0.56, 95%CI 0.49–0.65, respectively) and longer insertion and withdrawal times (≥ 4.00 vs. < 2.00 min: OR 1.96, 95%CI 1.68–2.29; OR 32.79, 95%CI 28.22–38.11, respectively) were associated with adenoma detection. Being screened by endoscopists with low or intermediate ADRs, compared to high ADRs, was positively associated with CRC incidence (multivariable: HR 4.71, 95%CI 2.65–8.38; HR 2.16, 95%CI 1.22–3.81, respectively).ConclusionsBowel preparation quality and longer insertion and withdrawal time are key for improving distal adenoma detection. Higher ADRs were associated with a lower risk of distal CRC.

A137 TRANSANAL ENDOSCOPIC COOPERATIVE SURGERY (TECS): COMBINED APPROACH FOR A LARGE POST-TRANSANAL RESECTION RECURRENCE. A CASE REPORT

Abstract Background Advancements in endoscopy and minimally invasive surgery have led to the development of organ-preserving resection techniques to manage rectal lesions. According to JGES, ESGE, and AGA, endoscopic mucosal dissection (ESD) is typically recommended for Kudo V/JNET 2b pit pattern, LST-NG/Paris Is/IIc/IIa+Is morphology, presence of submucosal fibrosis, and local residual/recurrent adenomas. ESD is not without its limitations including depth of resection, technical difficulty and time. In some instances, a transanal minimally invasive surgery (TAMIS) approach can overcome some of these limitations while also avoiding the morbidity of proctectomy. The ESD-TAMIS approach has been described by two groups in the USA and Germany demonstrating initial safety and feasibility for management of distal rectal adenomas. Purpose We present the first Canadian case to demonstrate the use of a combined ESD-TAMIS for the management of a large post-TAMIS recurrent rectal adenoma, involving the dentate line, not amenable to endoscopic resection or TAMIS alone. Method N/A Result(s) A healthy 78-yr-old woman was referred for consideration of ESD of a large recurrent low rectal adenomatous lesion which had undergone multiple prior endoscopic mucosal and TAMIS resections. Pathology from prior excisions never showed high grade dysplasia (HGD) or intramucosal cancer. The lesion was 4-5cm long and occupied 90% of the circumference of the lumen including the dentate line. It had Paris IIa+Is+IIb components with submucosal fibrosis. The pit pattern was JNET 2a/2b (Fig 1). Given the size and dramatic submucosal scarring, ESD was deemed extremely challenging, time consuming and would likely involve a full thickness resection. Similarly, given that the lesion involved the dentate line and the borders were difficult to delineate, a TAMIS would not be feasible. In collaboration with our surgical colleagues, we proceeded with the ESD-TAMIS. The borders of the lesion were first demarcated and marked endoscopically. Using standard ESD technique, a mucosal incision was performed on the anal side of the lesion, followed by submucosal dissection until sufficient space was created for the TAMIS platform. Then, using TAMIS technique, a full thickness resection was performed. The lesion was successfully removed en-bloc and pinned for pathology. The large size of the defect and proximity to the dentate line prevented surgical closure. Post-op course was complicated by fever successfully managed with antibiotics. Overall, the procedure was well tolerated. The final pathology revealed a tubulovillous adenoma with HGD and extensive submucosal fibrosis. Image Conclusion(s) A transanal endoscopic cooperative surgery combining ESD and TAMIS was safe and effective, combining the advantages of each procedural technique, in providing curative en-bloc resection of a recurrent large near-circumferential low rectal tubulovillous adenoma with HGD involving the dentate line. Here, we present the first reported Canadian case using this novel technique. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Risk factor analysis of malignant adenomas detected during colonoscopy.

Several studies have shown that colorectal adenomas are the most important precancerous lesions. The colonoscopic identification of groups with the high risk of malignant colorectal adenomas remains a controversial issue for clinicians. To evaluate the basic characteristics of colorectal adenomas with malignancy risk using high-grade dysplasia (HGD) as an alternative marker for malignant transformation. Data from Shanghai General Hospital between January 2017 and December 2021 were retrospectively analyzed. The primary outcome was the incidence of HGD in adenomas, which was used as a surrogate marker for the risk of malignancy. Odds ratios (ORs) for the HGD rate in adenomas were analyzed in relation to adenoma-related factors. A total of 9,646 patients identified with polyps during 57,445 screening colonoscopies were included in the study. Patients with flat polyps, sessile polyps, and pedunculated polyps represented 27.3% (N = 2,638), 42.7% (N = 4,114), and 30.0% (N = 2,894) of the total number, respectively. HGD was found in 2.41% (N = 97), 0.92% (N = 24), and 3.51% (N = 98) of sessile adenomas, flat adenomas, and pedunculated adenomas, respectively (P < 0.001). Multivariable logistic regression showed that polyp size (P < 0.001) but not shape (P > 0.8), was an independent predictor of HGD. Contrast to the diameter ≤1 cm, the OR value for diameters 1-2, 2-3, and >3 cm was 13.9, 49.3, and 161.6, respectively. The HGD incidence also increased in multiple adenomas (>3 vs. >1, ORs 1.582) and distal adenomas (distal vs. proximal adenomas, OR 2.252). Adenoma morphology (pedunculated vs. flat) was statistically significant in univariate analysis but not when size was included in the multivariate analysis. Besides, the incidence of HGD was also significantly higher in older patients (>64 vs. <50 years old, OR = 2.129). Sex (P = 0.681) was not statistically significant. All these associations were statistically significant (P < 0.05). The malignant potential of polyps is mostly affected by their size but not by their shape. In addition, distal location, multiple adenomas, and advanced age were also correlated with malignant transformation.

Reporting of Adenoma Detection by Segment: A Proposed New Quality Metric for Colonoscopy

Background and AimsThe adenoma detection rate (ADR), is a key quality metric for colonoscopy, but it might fail to measure differences in adenoma detection in different parts of the colon. Because many post-colonoscopy cancers arise in the proximal colon, differences in the ADR of proximal vs distal adenomas could be clinically important. Our aim was to determine the feasibility of measuring ADR for both the proximal and distal colon and to understand differences based on age, sex, and race. MethodsWe queried a large claims database (Health Care Service Corporation) to screen colonoscopies from 2016-2018 to determine the location and pathology of detected polyps. We measured the ADR in both the proximal (P-ADR) and distal (D-ADR) colon to determine differences in the ratio of P-ADR vs D-ADR by age, sex, and race. ResultsThe cohort included 93,163 women and 89,132 men. A progressive increase in both P-ADR and D-ADR occurs with advancing age, with the P-ADR/D-ADR ratio rising from 1.2 in patients under 40 years of age to 2.65 in patients age 75 and older, in both men and women. This ratio is affected by the experience of the endoscopist. A higher volume of procedures is directly related to higher polyp detection, specifically the P-ADR. ConclusionAs age advances, there is an increasing predominance of proximal adenomas relative to distal adenomas in both men and women, in all races. With appropriate coding, it is feasible to measure the ADR for the proximal and distal colon. Measurement of P-ADR could be an important new quality metric.

Site-specific Performance of ColonView (CV) Fecal Immunochemical Test (FIT) With Differences Between Proximal and Distal Colorectal Adenoma.

The aim of this study was to assess the diagnostic accuracy (DA) of a ColonView (CV) test in proximal versus distal colorectal adenoma (pCRA versus dCRA). The colorectal neoplasia (CRN) screening cohort included 5,090 individuals and 506/5,090 (10%) were eligible for the study. Finally, only 127/506 were included in the CRA analysis and hierarchical summary ROC (HSROC) curves were used to show the pooled overall DA of visually analyzed (VA) and automatically analyzed (AA) techniques in pCRA and dCRA detection. The overall specificity (Sp) of the AA technique for the pCRA and dCRA endpoint was 46% and 43%, respectively. The most sensitive AA test in pCRA patients showed 76% sensitivity (Se) versus 58% Se in dCRA patients. In the HSROC analysis, area under the curve (AUC) values were as follows: i) VA in pCRA: AUC=0.503, ii) AA in pCRA: AUC=0.560, iii) VA in dCRA: AUC=0.552 and iv) AA in dCRA: AUC=0.486. In Roccomp analysis, the statistically significant AUC values were available between VA and AA reading modes in pCRA (p=0.044) and in AA reading between pCRA and dCRA (p=0.024). As compared with the CRC endpoint, the DA value of the CV test is far inferior for the CRA endpoint, as determined by the AUC values.

Risk of developing metachronous colorectal neoplasia after the resection of proximal versus distal adenomas.

Current post-polypectomy guidelines do not consider adenoma location. We compared the risk of metachronous colorectal neoplasia (CRN) according to adenoma location. We collected data from 9710 patients who underwent follow-up colonoscopy after adenoma removal. Patients were classified according to baseline adenoma location: distal only (n=4665), proximal only (n=3827), and both sides (n=1218). The risk of metachronous CRN in patients with proximal only adenomas was higher than that in those with distal only adenomas (adjusted hazard ratio [aHR]=1.12, 95% confidence interval [CI]=1.04-1.21), while the risk of metachronous advanced CRN (ACRN) was not different between the two groups. Among patients aged <50 years, the risk of metachronous CRN in those with proximal only non-advanced adenomas (NAAs) was higher than that in those with only distal NAAs, while among patients aged ≥50 years, the risk in those with proximal only advanced adenomas (AAs) was higher than that in those with distal only AAs. However, the risk of metachronous ACRN did not differ based on adenoma location in patients aged <50 and ≥50 years. Proximal adenoma was associated with an increased risk of metachronous CRN, but not with an increased risk of metachronous ACRN, supporting the current guidelines recommending the same surveillance interval for distal and proximal adenoma without discrimination by adenoma location.

Endoscopic mucosal resection (EMR) versus endoscopic submucosal dissection (ESD) for resection of large distal non-pedunculated colorectal adenomas

Background: Endoscopic mucosal resection (EMR) is currently the most used technique for resection of large distal colorectal polyps. However, in large lesions EMR can often only be performed in a piecemeal fashion resulting in relatively low radical (R0)-resection rates and high recurrence rates. Endoscopic submucosal dissection (ESD) is a newer procedure that is more difficult resulting in a longer procedural time, but is promising due to the high en-bloc resection rates and the very low recurrence rates. Objective: To investigate whether Endoscopic mucosal resection (EMR) is superior to endoscopic submucosal dissection (ESD) for resection of large distal non-pedunculated colorectal adenomas. Methods: PubMed, Google scholar and Science direct were searched using the following keywords: Endoscopic mucosal resection, endoscopic submucosal dissection and Colorectal adenomas. The authors also screened references from the relevant literature, including all the identified studies and reviews, only the most recent or complete study was included. Documents in a language apart from English have been excluded as sources for interpretation was not found. Papers apart from main scientific studies had been excluded: documents unavailable as total written text, conversation, conference abstract papers and dissertations. Conclusion: EMR is safe and effective for treating colorectal adenomas.

Weight Change and Incident Distal Colorectal Adenoma Risk in the PLCO Cancer Screening Trial.

BackgroundAlthough obesity is a known risk factor, the impact of weight change on colorectal adenoma risk is less clear and could have important implications in disease prevention. We prospectively evaluated weight change in adulthood and incident colorectal adenoma.MethodsWe assessed weight change during early-late (age 20 years to baseline, ie, ages 55-74 years), early-middle (20-50 years), and middle-late (50 years-baseline) adulthood using self-reported weight data in relation to incident distal adenoma in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (cases = 1053; controls = 16 576). For each period, we defined stable weight as greater than −0.5 kg to less than or equal to 1 kg/5 years, weight loss as less than or equal to −0.5 kg/5 years, and weight gain as greater than 1-2, greater than 2-3, or greater than 3 kg/5 years. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression; all tests were 2-sided.ResultsCompared with stable weight, weight loss during early-late adulthood was associated with reduced adenoma risk (OR = 0.54, 95% CI = 0.34 to 0.86), particularly among those who were overweight or obese at age 20 years (OR = 0.39, 95% CI = 0.18 to 0.84). Results were similar for early-middle adulthood but less pronounced for middle-late adulthood. Weight gain greater than 3 kg/5 years during early-late adulthood was associated with increased risk (OR = 1.30, 95% CI = 1.07 to 1.58, Ptrend < .001). Findings appeared stronger among men (OR for >3 kg/5 years = 1.41, 95% CI = 1.11 to 1.80) than women (OR = 1.09, 95% CI = 0.79 to 1.50, Pinteraction = .21).ConclusionsWeight loss in adulthood was associated with reduced adenoma risk, particularly for those who were overweight or obese, whereas weight gain greater than 3 kg/5 years increased risk. Findings underscore the importance of healthy weight maintenance throughout adulthood in preventing colorectal adenoma.

Colocalization with MMP-7 in the Distal Colon is Crucial for Syndecan-2 Shedding in Dextran Sulfate Sodium-Induced Colitis Mice.

IntroductionSyndecan-2 expression is elevated during chronic inflammation and cancer development, and its shedding is observed in cancer patients. However, it remained unknown whether inflammation triggers syndecan-2 shedding.MethodsThe colitis model was produced in C57BL/6 mice by oral administration of 2–3% dextran sulfate sodium (DSS) in the drinking water. Syndecan-2 and MMP-7 expression levels in tissues and cells were detected by real-time PCR, Western blotting, and immunohistochemistry. Shed syndecan-2 levels were detected by slot blotting. For tissue culture, colon tissues were divided into proximal, transverse, and distal parts, and incubated in culture media.ResultsIn C57BL/6 mice with DSS-induced colitis, syndecan-2 shedding began to increase after week 12 of chronic inflammation and continued to increase at week 15. The level of shed syndecan-2 correlated with the colocalization of syndecan-2 and MMP-7 in distal colon tissues. The mRNA expression of IL-6 was increased specifically in trans-distal colon tissues from weeks 9 to 15. IL-6 induced syndecan-2 expression and shedding and MMP-7 expression in ex vivo-cultured distal colon tissues and adenoma cell lines derived from the distal colon. IL-6 treatment induced STAT3 phosphorylation and MMP-7 expression in DLD-1 cells. The application of MMP-7 to ex vivo-cultured colon tissues increased the shedding of syndecan-2 to the culture medium.ConclusionOur findings suggest that chronic inflammation induces syndecan-2 shedding via the site-specific colocalization of syndecan-2 with MMP-7 in the distal colon.

Aspirin, ibuprofen, and reduced risk of advanced colorectal adenoma incidence and recurrence and colorectal cancer in the PLCO Cancer Screening Trial.

Studying the differential impact of aspirin and other nonsteroidal anti-inflammatory drugs across the stages of colorectal neoplasia from early adenoma to cancer is critical for understanding the benefits of these widely used drugs. With 13 years of follow-up, the authors prospectively evaluated the association between aspirin and ibuprofen use and incident distal adenoma (1221 cases), recurrent adenoma (862 cases), and incident colorectal cancer (CRC; 2826 cases) among men and women in the population-based Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. With multivariable-adjusted models, odds ratio (ORs) and 95% confidence intervals (CIs) for adenoma incidence and recurrence and hazard ratios (HRs) and 95% CIs for incident CRC were determined. The authors observed a significantly reduced risk of incident adenoma with ibuprofen use (≥30 vs <4 pills per month: OR, 0.76 [95% CI, 0.60-0.95]; Ptrend = .04), particularly advanced adenoma (OR, 0.48 [95% CI, 0.28-0.83]; Ptrend = .005). Among those with a previous adenoma detected through screening, aspirin use was associated with a decreased risk of advanced recurrent adenoma (≥30 vs <4 pills per month: OR, 0.56 [95% CI, 0.36-0.87]; Ptrend = 0.006). Both aspirin (HR, 0.88 [95% CI, 0.81-0.96]; Ptrend <.0001) and ibuprofen use (HR, 0.81 [95% CI, 0.70-0.93); Ptrend = 0.003) ≥30 versus <4 pills per month were significantly associated with reduced CRC risk. In this large prospective study with long-term follow-up, a beneficial role for not only aspirin, but also ibuprofen, in preventing advanced adenoma and curbing progression to recurrence and cancer among older adults was observed.

Bacterial-Driven Inflammation and Mutant BRAF Expression Combine to Promote Murine Colon Tumorigenesis That Is Sensitive to Immune Checkpoint Therapy.

Colorectal cancer is multifaceted, with subtypes defined by genetic, histologic, and immunologic features that are potentially influenced by inflammation, mutagens, and/or microbiota. Colorectal cancers with activating mutations in BRAF are associated with distinct clinical characteristics, although the pathogenesis is not well understood. The Wnt-driven multiple intestinal neoplasia (MinApcΔ716/+) enterotoxigenic Bacteroides fragilis (ETBF) murine model is characterized by IL17-dependent, distal colon adenomas. Herein, we report that the addition of the BRAF V600E mutation to this model results in the emergence of a distinct locus of midcolon tumors. In ETBF-colonized BRAF V600E Lgr5 CreMin (BLM) mice, tumors have similarities to human BRAF V600E tumors, including histology, CpG island DNA hypermethylation, and immune signatures. In comparison to Min ETBF tumors, BLM ETBF tumors are infiltrated by CD8+ T cells, express IFNγ signatures, and are sensitive to anti-PD-L1 treatment. These results provide direct evidence for critical roles of host genetic and microbiota interactions in colorectal cancer pathogenesis and sensitivity to immunotherapy. SIGNIFICANCE: Colorectal cancers with BRAF mutations have distinct characteristics. We present evidence of specific colorectal cancer gene-microbial interactions in which colonization with toxigenic bacteria drives tumorigenesis in BRAF V600E Lgr5 CreMin mice, wherein tumors phenocopy aspects of human BRAF-mutated tumors and have a distinct IFNγ-dominant immune microenvironment uniquely responsive to immune checkpoint blockade.This article is highlighted in the In This Issue feature, p. 1601.

Divergent detection rates of fecal immunochemical test and questionnaire-based risk assessment for detecting proximal and distal advanced colorectal adenomas

Divergent detection rates of fecal immunochemical test and questionnaire-based risk assessment for detecting proximal and distal advanced colorectal adenomas

Dairy intake during adolescence and risk of colorectal adenoma later in life

BackgroundHigher dairy intake during adulthood has been associated with lower colorectal cancer risk. As colorectal carcinogenesis spans several decades, we hypothesised that higher dairy intake during adolescence is associated with lower risk of colorectal adenoma, a colorectal cancer precursor.MethodsIn 27,196 females from the Nurses’ Health Study 2, aged 25–42 years at recruitment (1989), who had completed a validated high school diet questionnaire in 1998 and undergone at least one lower bowel endoscopy between 1998 and 2011, logistic regression for clustered data was used to calculate odds ratios (ORs) and 95% confidence intervals (CI).ResultsColorectal adenomas were diagnosed in 2239 women. Dairy consumption during adolescence was not associated with colorectal adenoma risk (OR highest vs. lowest [≥4 vs. ≤1.42 servings/day] quintile [95% CI] 0.94 [0.80, 1.11]). By anatomical site, higher adolescent dairy intake was associated with lower rectal (0.63 [0.42, 0.95]), but not proximal (1.01 [0.80, 1.28]) or distal (0.97 [0.76, 1.24]) colon adenoma risk. An inverse association was observed with histologically advanced (0.72 [0.51, 1.00]) but not non-advanced (1.07 [0.86, 1.33]) adenoma.ConclusionsIn this large cohort of younger women, higher adolescent dairy intake was associated with lower rectal and advanced adenoma risk later in life.

Long term outcomes of colon polyps with high grade dysplasia following endoscopic resection

BackgroundThe risk of recurrent colonic adenoma associated with high-grade dysplasia (HGD) colon polyps at baseline colonoscopy remains unclear. We conducted a clinical cohort study with patients who underwent polypectomy during screen colonoscopy to assess recurrent colonic adenoma risk factors.Methods11,565 patients at our facility underwent screen colonoscopy between September 1998 and August 2007. Data from patients with HGD colon polyps who had undergone follow-up colonoscopy were included for analysis.ResultsData from 211 patients was included. Rates of metachronous adenoma and advanced adenoma at follow-up were 58% and 20%, respectively. Mean follow-up period was 5.5 ± 1.8 (3–12) years. Univariate logistic regression analysis revealed that an adenoma count of ≥ 3 at baseline colonoscopy was strongly associated with overall recurrence, multiple recurrence, advanced recurrence, proximal recurrence, and distal adenoma recurrence with odds ratios of 4.32 (2.06–9.04 95% CI), 3.47 (1.67–7.22 95% CI), 2.55 (1.11–5.89 95% CI), 2.46 (1.16–5.22 95% CI), 2.89 (1.44–5.78 95% CI), respectively. Multivariate analysis revealed gender (male) [P = 0.010; OR 3.09(1.32–7.25 95% CI)] and adenoma count ≥ 3 [P = 0.002; OR 3.08(1.52–6.24 95% CI)] at index colonoscopy to be significantly associated with recurrence of advanced adenoma.ConclusionRecurrence of colonic adenoma at time of follow-up colonoscopy is common in patients who undergo polypectomy for HGD colon adenomas during baseline colonoscopy. Risk of further developing advanced adenomas is associated with gender and the number of colon adenomas present.

Comprehensive Assessment of Diet Quality and Risk of Precursors ofEarly-Onset Colorectal Cancer.

The role of poor diet quality in the rising incidence of colorectal cancer (CRC) diagnosed younger than age 50 years has not been explored. Based on molecular features of early-onset CRC, early-onset adenomas are emerging surrogate endpoints. In a prospective cohort study (Nurses' Health Study II), we evaluated 2 empirical dietary patterns (Western and prudent) and 3 recommendation-based indexes (Dietary Approaches to Stop Hypertension [DASH], Alternative Mediterranean Diet [AMED], and Alternative Healthy Eating Index [AHEI]-2010) with risk of early-onset adenoma overall and by malignant potential (high-risk: ≥1 cm, tubulovillous or villous histology, high-grade dysplasia, or ≥3 adenomas), among 29 474 women with 1 or more lower endoscopy before age 50 years (1991-2011). Multivariable logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). We documented 1157 early-onset adenomas with 375 at high risk. Western diet was positively associated, whereas prudent diet, DASH, AMED, and AHEI-2010 were inversely associated with risk of early-onset adenoma. The associations were largely confined to high-risk adenomas (the highest vs lowest quintile: Western, OR = 1.67, 95% CI = 1.18 to 2.37; prudent, OR = 0.69, 95% CI = 0.48 to 0.98; DASH, OR = 0.65, 95% CI = 0.45 to 0.93; AMED, OR = 0.55, 95% CI = 0.38 to 0.79; AHEI-2010, OR = 0.71, 95% CI = 0.51 to 1.01; all Ptrend ≤ .03), driven by those identified in the distal colon and rectum (all Ptrend ≤ .04, except AMED: Ptrend = .14). Poor diet quality was associated with an increased risk of early-onset distal and rectal adenomas of high malignant potential. These findings provide preliminary but strong support to the role of diet in early-onset CRC.

Analysis of proliferation and apoptosis, MUC-1 and Cdx-2 expression in distal colonic polyps

Background. The universal molecular characteristics of malignancy are activation of cell proliferation and inactivation of apoptotic cell death. Besides genes-regulators of the processes other molecules are involved, including mucins and Cdx-2. Aim . To conduct comparative and correlation analysis of indexes of immunohistochemical expression of Ki-67, p53, caspase-3, as well as MUC-1 and Cdx-2 in distal colonic polyps. Methods. Pathohistological and immunohistochemical studies of biopsies of adenomas and hyperplastic polyps from 40 patients were carried out. Results. Distal colonic polyps are characterized by medium proliferation level: the median of Ki-67 expression for hyperplastic polyps is 42,20 (35,27; 52,38) %, while the median for adenomas is 65,39 (52,28; 76,23) % (р˂0,05). The polyps are characterized by low p53 expression levels: the median of the marker expression for hyperplastic polyps is 1,53 (1,17; 3,16) %, for adenomas – 9,15 (8,26; 12,39) % (р˂0,05). The studied polyps are characterized by low apoptosis levels: the median of caspase-3 expression for hyperplastic polyps is 33,78 (30,28; 42,34) CUOD, for adenomas – 22,19 (16,84; 40,51) CUOD (р˂0,05). Distal colonic polyps are characterized by medium MUC-1 and Cdx-2 expression levels: the medians of the markers expression for hyperplastic polyps are 62,13 (34,20; 71,85) CUOD and 71,81 (62,36; 77,77) CUOD, for adenomas – 80,25 (52,14; 95,21) CUOD and 95,14 (81,19; 112,17) CUOD, respectively (р˂0,05). The correlation analysis revealed several correlations: reverse medium strength correlation between p53 and caspase-3 expression levels (r = -0,57, р˂0,05), direct medium strength correlation between caspase-3 and MUC-1 expression levels (r = 0,52, p˂0,05) take place in hyperplastic polyps, whereas reverse strong correlation between caspase-3 and MUC-1 expression levels 1 (r = -0,88, p˂0,05) takes place in adenomas. Conclusions. Distal colonic adenomas differ by higher proliferation and p53 expression levels, comparing to hyperplastic polyps, and by lower apoptosis level that is associated with higher MUC-1 expression level as well. Hyperplastic polyps differ by higher apoptosis level that is associated with lower MUC-1 expression level. Cdx-2 expression increases on benign adenoma stage and does not correlate with proliferation and apoptosis indexes.

Distal common bile duct adenoma

Distal common bile duct adenoma

Distal common bile duct adenoma

Distal common bile duct adenoma

Abstract LB-158: Weight change in adulthood and colorectal adenoma incidence in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Abstract Obesity is a known risk factor for colorectal cancer, but the influence of weight change during one's lifetime on colorectal adenoma, precursor to colorectal cancer, is less understood. We prospectively investigated the association between weight change in different time periods in adulthood and the risk of colorectal adenoma. We included 1,041 incident distal colorectal adenoma cases (negative on baseline trial flexible sigmoidoscopy screen and positive on follow-up trial sigmoidoscopy screen 3-5 years later) and 16,394 controls (negative on both trial screens) from the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We required participants to have no history of colorectal polyps, other colon comorbidities or cancer. Using self-reported weight data at trial baseline, we estimated odds ratios (OR) and 95% confidence intervals (95% CI) for early-late (age 20-baseline, i.e. ages 55-74), early-middle (age 20-50) and middle-late (age 50-baseline) adulthood weight change with colorectal adenoma using logistic regression. We defined the weight stable group (referent) as weight loss &amp;lt;0.5 kg/5 years or weight gain ≤1 kg/5 years. We defined the weight loss group as those who lost ≥0.5 kg/5 years. We included three weight gain groups: &amp;gt;1 to ≤2, &amp;gt;2 to ≤3 and &amp;gt;3 kg/5 years. We adjusted models for starting BMI (age 20 or 50), age, sex, race, smoking and other factors including diet. Compared to weight stable participants, weight loss in early-late adulthood was inversely associated with colorectal adenoma (OR=0.6, 95% confidence interval (CI): 0.3-0.9); results were similar for early-middle adulthood (OR=0.5, 95% CI: 0.3-0.8), but less pronounced for middle-late adulthood (OR=0.8, 95% CI: 0.7-1.0). Early-late adulthood weight gain of &amp;gt;3 kg/5 years was associated with higher odds of adenoma (OR=1.3, 95% CI: 1.1-1.6); results were similar for middle-late adulthood (OR=1.2, 95% CI: 1.0-1.4), but less pronounced for early-middle adulthood (OR=1.1, 95% CI: 0.9-1.3). We observed some evidence of a stronger association for men than women (for early-late adulthood weight gain &amp;gt;3 kg/5 years, OR for men=1.4, 95% CI: 1.1-1.8; OR for women=1.1, 95% CI: 0.8-1.5), although the interaction was not statistically significant (p-int=0.65). When we stratified by starting BMI, we observed a significantly decreased risk of colorectal adenoma with weight loss from early-late adulthood among those who were overweight/obese at age 20 (OR=0.4, 95% CI: 0.2-0.9). Findings suggest that weight loss in adulthood for those who are overweight/obese is associated with a reduced risk of colorectal adenoma. In addition, our results suggest that a modest rate of weight gain in adulthood of &amp;gt;3 kg/5 years is associated with an increased risk of colorectal adenoma. These findings underscore the importance of healthy weight maintenance in adulthood in preventing colorectal adenoma. Citation Format: Shisi He, Sonja I. Berndt, Andrew T. Kunzmann, Cari M. Kitahara, Wen-Yi Huang, Kathryn Hughes Barry. Weight change in adulthood and colorectal adenoma incidence in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-158.

Does Colon Polyp Surveillance Improve Patient Outcomes?

Colon polyp surveillance now accounts for 25% of all colonoscopies performed. The evidence that colonoscopy surveillance reduces colorectal cancer (CRC) incidence or mortality is weak. The biology of the baseline lesions and quality of the baseline exam are two primary factors contributing to post-colonoscopy CRC. Prior recommendations for surveillance were based largely on the likelihood that patients with adenomas would develop advanced adenomas, a surrogate for CRC. There is now evidence that baseline colonoscopy findings are strongly associated with the risk of incidence or death from CRC. This evidence provides a basis for updated evidence-based recommendations for surveillance. In addition, there is also growing evidence that the quality of the baseline exam is an important predictor of the likelihood of developing post-colonoscopy CRC.