Nonpolypoid Colorectal Neoplasms Research Articles

Endoscopic Removal of Premalignant Lesions Reduces Long-Term Colorectal Cancer Risk: Results From the Japan Polyp Study

To date, no regional evidence of long-term colorectal cancer (CRC) risk reduction after endoscopic premalignant lesion removal has been established. We aimed to analyze this over a long-term follow-up evaluation. This was a prospective cohort study of participants from the Japan Polyp Study conducted at 11 Japanese institutions. Participants underwent scheduled follow-up colonoscopies after a 2-round baseline colonoscopy process. The primary outcome was CRC incidence after randomization. The observed/expected ratio of CRC was calculated using data from the population-based Osaka Cancer Registry. Secondary outcomes were the incidence and characteristics of advanced neoplasia (AN). A total of 1895 participants were analyzed. The mean number of follow-up colonoscopies and the median follow-up period were 2.8 years (range, 1-15 y) and 6.1 years (range, 0.8-11.9 y; 11,559.5 person-years), respectively. Overall, 4 patients (all males) developed CRCs during the study period. The observed/expected ratios for CRC in all participants, males, and females, were as follows: 0.14 (86% reduction), 0.18, and 0, respectively, and 77 ANs were detected in 71 patients (6.1 per 1000 person-years). Of the 77 ANs detected, 31 lesions (40.3%) were laterally spreading tumors, nongranular type. Nonpolypoid colorectal neoplasms (NP-CRNs), including flat (<10 mm), depressed, and laterally spreading, accounted for 59.7% of all detected ANs. Furthermore, 2 of the 4 CRCs corresponded to T1 NP-CRNs. Endoscopic removal of premalignant lesions, including NP-CRNs, effectively reduced CRC risk. More than half of metachronous ANs removed by surveillance colonoscopy were NP-CRNs. The Japan Polyp Study: University Hospital Medical Information Network Clinical Trial Registry: University Hospital Medical Information Network Clinical Trial Registry, C000000058; cohort study: UMIN000040731.

Correction: Effective use of image-enhanced endoscopy and endoscopic submucosal dissection for multiple flat non-polypoid colorectal neoplasms.

Correction: Effective use of image-enhanced endoscopy and endoscopic submucosal dissection for multiple flat non-polypoid colorectal neoplasms.

Effective use of image-enhanced endoscopy and endoscopic submucosal dissection for multiple flat non-polypoid colorectal neoplasms.

Effective use of image-enhanced endoscopy and endoscopic submucosal dissection for multiple flat non-polypoid colorectal neoplasms.

Molecular pathways in post-colonoscopy versus detected colorectal cancers: results from a nested case-control study.

Post-colonoscopy colorectal cancers (PCCRCs) pose challenges in clinical practice. PCCRCs occur due to a combination of procedural and biological causes. In a nested case-control study, we compared clinical and molecular features of PCCRCs and detected CRCs (DCRCs). Whole-genome chromosomal copy number changes and mutation status of genes commonly affected in CRC were examined by low-coverage WGS and targeted sequencing, respectively. MSI and CIMP status was also determined. In total, 122 PCCRCs and 98 DCRCs with high-quality DNA were examined. PCCRCs were more often located proximally (P < 0.001), non-polypoid appearing (P = 0.004), early stage (P = 0.009) and poorly differentiated (P = 0.006). PCCRCs showed significantly less 18q loss (FDR < 0.2), compared to DCRCs. No significant differences in mutations were observed. PCCRCs were more commonly CIMP high (P = 0.014) and MSI (P = 0.029). After correction for tumour location, only less 18q loss remained significant (P = 0.005). Molecular features associated with the sessile serrated lesions (SSLs) and non-polypoid colorectal neoplasms (CRNs) are more commonly seen in PCCRCs than in DCRCs. These together with the clinical features observed support the hypothesis that SSLs and non-polypoid CRNs are contributors to the development of PCCRCs. The future focus should be directed at improving the detection and endoscopic removal of these non-polypoid CRN and SSLs. NTR3093 in the Dutch trial register ( www.trialregister.nl ).

Tip-in Endoscopic Mucosal Resection for 15- to 25-mm Colorectal Adenomas: A Single-Center, Randomized Controlled Trial (STAR Trial).

One-piece endoscopic mucosal resection (EMR) for lesions >15 mm is still unsatisfactory, and attempted 1-piece EMR for lesions >25 mm can increase perforation risk. Therefore, modifications to ensure 1-piece EMR of 15- to 25-mm lesions would be beneficial. The aim of this study was to investigate whether Tip-in EMR, which anchors the snare tip within the submucosal layer, increases en bloc resection for 15- to 25-mm colorectal lesions compared with EMR. In this prospective randomized controlled trial, patients with nonpolypoid colorectal neoplasms of 15-25 mm in size were recruited and randomly assigned in a 1:1 ratio to undergo Tip-in EMR or standard EMR, stratified by age, sex, tumor size category, and tumor location. The primary endpoint was the odds ratio of en bloc resection adjusted by location and size category. Adverse events and procedure time were also evaluated. We analyzed 41 lesions in the Tip-in EMR group and 41 lesions in the EMR group. En bloc resection was achieved in 37 (90.2%) patients undergoing Tip-in EMR and 30 (73.1%) who had EMR. The adjusted odds ratio of en bloc resection in Tip-in EMR vs EMR was 3.46 (95% confidence interval: 1.06-13.6, P = 0.040). The Tip-in EMR and EMR groups did not differ significantly in adverse event rates (0% vs 4.8%) or median procedure times (7 vs 5 minutes). In this single-center randomized controlled trial, we found that Tip-in EMR significantly improved the en bloc resection rate for nonpolypoid lesions 15-25 mm in size, with no increase in adverse events or procedure time.

Randomised comparison of postpolypectomy surveillance intervals following a two-round baseline colonoscopy: the Japan Polyp Study Workgroup

ObjectiveTo assess whether follow-up colonoscopy after polypectomy at 3 years only, or at 1 and 3 years would effectively detect advanced neoplasia (AN), including nonpolypoid colorectal neoplasms (NP-CRNs).DesignA prospective multicentre...

Post-Colonoscopy Rapidly Progressive Colorectal Cancer

Colorectal cancer (CRC) surveillance guidelines are designed to decrease the incidence of cases. However, small subgroups of CRC are discovered after a screening examination in which no suspicious lesions were detected. Post colonoscopy CRC is thought to be multifactorial due to technical factors or distinct tumor biology playing an important role in pathogenesis. A 58 year old female presented with constipation, hematochezia and weight loss. No past medical history, & family histroy was non-contributory. She underwent a screening colonoscopy revealing internal hemorrhoids. One year later, patient had worsening symptoms, CT abdomen showed transverse colon mural thickening with abrupt luminal narrowing. Repeat colonoscopy revealed a 3-5 cm stricture in the transverse colon with biopsy consistent with hyperplastic changes. Given the high suspicion of malignancy, repeat biopsy showed moderately differentiated invasive adenocarcinoma, and microsatellite instability (MSI) negativity. Repeat CT for staging at 3 months revealed omental metastasis & partial bowel obstruction. Patient underwent exploratory laparotomy which revealed diffuse carcinomatosis throughout the abdominal wall, small bowel, & large lesion in the transverse colon. Patient underwent palliative colonic stent placement and chemotherapy. Interval colorectal carcinoma (iCRC) is defined as CRC appearing after a negative screening exam, & before the date of the next recommended screening. A recent meta-analysis showed a prevalence of 3.7% of cases if ICRC. Risk factors for iCRC include tumor biology, technical factors, nonpolypoid colorectal neoplasms, serrated lesions, and hereditary cancer syndromes. iCRC most commonly seen in the proximal colon, have mucinous histology, MSI positivity, & are associated with IBD and diverticular disease. Interestingly, iCRC has a 37% lower risk of mortality when compared to detected CRC. They also have similar one year survival rate compared to those who develop CRC after 10 years from last colonoscopy. Our case is unique since our patient developed a rapidly progressive iCRC despite no family history, MSI negativity, and compliant with the colonoscopy surveillance guidelines. Current colonoscopy surveillance guidelines may be inadequate to prevent such cases of interval colorectal cancers. Further research is needed to determine whether these interval colorectal cancers arise as a result of missed lesions or accelerated neoplastic progression.1577_A Figure 1. Neoplastic cells in cords and glandular pattern, at right lower corner.1577_B Figure 2. Neoplastic glands consists of markedly atypical cells with nuclear pleomorphism and nuclear hyperchromasia.1577_C Figure 3. Transverse colon stricture

Update on the role of chromoendoscopy in colonoscopic surveillance of patients with Lynch syndrome.

(Virtual) chromoendoscopy (CE) improves the detection of small or flat colorectal polyps; however, the evidence in high-risk groups, such as patients of Lynch syndrome (LS), is low. Our aim was to identify and update the evidence for the recommendations regarding surveillance of LS patients, for which the current underlying evidence for use of (virtual) CE was explored. A systematic literature search in PubMed, EMBASE, and Cochrane library was conducted, for all studies comparing (virtual) CE with white-light endoscopy in LS patients. Studies are explained in detail, with special attention to study design, type of (virtual) CE, and timing of polypectomy. Eight studies (409 patients) were included. Five were nonrandomized back-to-back studies and three were randomized back-to-back studies (one parallel and two cross-over design). In six studies the polyps were directly removed, while in two studies polyps were removed only during the second caecal withdrawal. Five studies researched CE with indigo carmine and three studies investigated virtual CE. Due to the heterogeneity between studies, no statistical analysis could be performed. There was a large variety in study design, timing of polypectomy, different (virtual) CE techniques and the patients that were included. Based on current literature, no firm conclusions can be drawn with respect to the additional value of (virtual) CE in the surveillance of patients with LS. However, training of endoscopists in detection and removal of nonpolypoid colorectal neoplasms is crucial, as well as stricter adherence to LS surveillance guidelines in daily clinical practice. For future research, standardization in study designs is needed.

Advances in image enhancement in colonoscopy for detection of adenomas.

High-quality colonoscopy is mandatory to prevent adenoma recurrence and colorectal cancer. In the past few years, technical advances have been developed with the purpose of improving adenoma detection rate (ADR), one of the most important validated colonoscopy quality benchmarks. Several techniques or devices are used to optimize visualization: observation techniques; add-on devices; auxiliary imaging devices; colonoscopes with increased field of view; and colonoscopes with an integrated inflatable reusable balloon. Image-enhanced endoscopy (IEE) facilitates the detection and characterization of polyps and especially nonpolypoid colorectal neoplasms. Indigo carmine is the most frequently used dye in colonoscopy as it deposits in depressed areas, improving detection of flat and depressed lesions. Virtual chromoendoscopy has emerged as an effective contrast enhancement technology without the limitation of preparing dyes and applying them through the colonoscope working channel. Narrow-band imaging (NBI) enhances the capillary pattern and surface of the mucosa using optical filters, and second-generation NBI provides a twofold brighter image than the previous system, yielding promising ADR results. Moreover, a second-generation blue laser imaging system, LASEREO, has been reported to improve not only polyp detection rate but also ADR, becoming a promising IEE modality. Herein, we describe technical advances in colonoscopy imaging and their effect on ADR.

Patients With Nonpolypoid (Flat and Depressed) Colorectal Neoplasms at Increased Risk for Advanced Neoplasias, Compared With Patients With Polypoid Neoplasms.

Nonpolypoid colorectal neoplasms (NP-CRNs) are more likely to contain high-grade dysplasia or early-stage cancer than polypoid neoplasms. We aimed to determine the long-term outcomes of patients with at least 1 NP-CRN. We performed a longitudinal cohort study of 4454 patients at a Veterans' Affairs hospital who underwent colonoscopy from 2000 through 2005; 341 were found to have 1 or more NP-CRNs and were matched (3:1) with patients found to have 1 or more polypoid neoplasms (controls, n= 1025). We collected and analyzed data on baseline colonoscopy findings and first follow-up colonoscopy results through August 2014. We calculated the incidence of advanced neoplasia at first follow-up colonoscopy, as defined by the presence of ≥1 tubular or sessile serrated adenomas ≥10 mm in diameter, tubulovillous adenoma, high-grade dysplasia, or invasive cancer. A significantly higher proportion of patients with 1 or more NP-CRNs (16.0%) were found to have advanced neoplasia at their first follow-up colonoscopy than controls (8.6%); the adjusted risk ratio was 1.6 (95% confidence interval, 1.05-2.6; P= .03). A significantly higher proportion ofpatients with 1 or more NP-CRNs were found to have additional NP-CRNs at the follow-up colonoscopy (17%) than controls (7%; relative risk, 2.3; 95% confidence interval, 1.5-3.5; P<.001). Similar proportions of patients in each group developed cancers after colonoscopy. In a longitudinal cohort study, we found that patients with NP-CRN were more likely to develop additional NP-CRNs and to have advanced neoplasms at their first follow-up colonoscopy than patients with only polypoid neoplasms. However, patients with NP-CRN were not more likely to develop cancers after colonoscopy when surveillance guidelines were followed. Larger studies are needed to determine risk of colorectal cancer in patients with NP-CRN.

970 High Rate of Advanced Neoplasia At Surveillance in Patients With Nonpolypoid (Flat and Depressed) Colorectal Neoplasms: Longitudinal Matched Cohort Study

970 High Rate of Advanced Neoplasia At Surveillance in Patients With Nonpolypoid (Flat and Depressed) Colorectal Neoplasms: Longitudinal Matched Cohort Study Sarah K. McGill*, Roy M. Soetikno, Robert V. Rouse, Hobart Lai, Tonya Kaltenbach Division of Gastroenterology, University of North Carolina, Chapel Hill, NC; Division of Gastroenterology, Veterans Affairs Palo Alto Health Care System, Stanford University School of Medicine, Palo Alto, CA; Division of Gastroenterology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA Background/Aims: Nonpolypoid colorectal neoplasms (NP-CRN) are more likely to harbor high-grade dysplasia or early cancer compared to those that are polypoid. However, it is unknown whether patients with NP-CRN have a propensity to develop advanced neoplasia at higher rates compared to patients with polypoid neoplasia alone. We aimed to determine the risk of advanced neoplasia at first surveillance colonoscopy in patients with at least one NP-CRN compared to patients with only polypoid neoplasia. Methods: We performed a longitudinal cohort study of patients undergoing elective colonoscopy from 2000-2004 found to have R1 NP-CRN, and then matched them in a 3:1 manner with control patients found to have one or more polypoid neoplasms in the same year. We extensively reviewed clinical, endoscopic and pathologic digital records, and followed surveillance colonoscopy data to 2014. We calculated the risk of advanced neoplasia at surveillance for our primary outcome, using the standard definition of advanced neoplasia: R1 tubular or sessile serrated adenomas R10 mm, tubulovillous adenoma, high-grade dysplasia, or invasive cancer. Advanced neoplasia diagnoses were reviewed by a GI pathologist. Results: We identified 4454 patients who underwent colonoscopy over the 5-year period, and studied 341 (7.7%; 95% CI: 6.9-8.5%) with R1 NP-CRN and 1025 matched controls with R1 polypoid neoplasm. Patients with NP-CRNs had a significantly higher rate of advanced neoplasia at surveillance colonoscopy than patients with polypoid neoplasia (16.1% vs. 8.8%, risk ratio 1.8, 95% CI 1.3-2.7, p!.001). The advanced neoplasms detected at surveillance colonoscopy in patients with NP-CRN compared to patients with polypoid neoplasms were more likely to be nonpolypoid (60% vs. 33%, RR 1.8), and located in the proximal colon (72% vs 54%, RR 1.3). Overall, flat neoplasms at surveillance were 5 times more likely to be advanced than polypoid neoplasms (RR 5.0, 95% CI 3.7-6.7, p!.001). Patients with NP-CRNs compared to controls also had higher rates of advanced neoplasia (63% vs. 26%, p!.001) and harbored more neoplasia (mean SD 3.2 2.9 vs. 2.1 1.6, p!.001) at baseline exam. One or more NP-CRN were found on surveillance in 17% of patients with NP-CRN at baseline, compared to only 7% of control patients (RR 2.3, 95% CI 1.6-3.3). Demographic characteristics of patients at baseline were similard mean age was 66 ( SD10) and most were men (98%) and tobacco users (64%). However, NSAID use was more common in patients with NP-CRN (54% vs 35%) and the indication for baseline colonoscopy was more likely to be screening in control patients (47% vs 41%). Conclusions: Patients with NP-CRN have a high rate of advanced neoplasia at baseline and surveillance examinations and moreover, a significantly greater risk for developing advanced neoplasia than patients with polypoid neoplasia alone.

Sa1639 Impact of Bowel Preparation Quality on Detection of Non-Polypoid Colorectal Neoplasms and Their Prevalence in Average-Risk Screening Colonoscopy

family history, colonoscopy history, or withdrawal time of colonoscopy; prior history of invasive CRC, inflammatory bowel disease, or familial adenomatous polyposis. Patients who had undergone colonoscopy performed by a colonoscopist who had experience with!30 colonoscopies during the study period were also excluded. Colonoscopists who participated in the study were divided into following 3 groups, based on median withdrawal time of negative colonoscopy:!6 min (group A); 6-9 min (group B); and R10 min (group C). We analyzed the relationship between the withdrawal time group and adenoma detection rate using multiple logistic regression. The odds ratios were adjusted according to age, sex, past history of CRC, family history of CRC, past history of colonoscopy, and whether or not a distal attachment was used. Results: The final analysis included 4988 patients. Compared with group A, the odds ratios for detection of any adenoma or cancer by colonoscopists in group B, and group C were 1.53 (95% confidence interval [CI], 1.15-2.04) and 1.95 (95% CI, 1.45-2.63), respectively. For detection of advanced neoplasia, the respective odds ratios were 1.61 (95% CI, 0.95-2.73) and 1.97 (95% CI, 1.15-3.37). Conclusions: The results of this study suggest that a colonoscopy withdrawal time of over 6 min would be a useful quality indicator of colonoscopy in the Japanese setting. Relationship between colonoscopist groups and adenoma detection rates

Screening colonoscopy: what is the most reliable modality for the detection and characterization of colorectal lesions?

Colonoscopy is considered the best modality for the detection and treatment of colorectal polyps. However, some polyps still may not be detected. Although conventional white-light endoscopy is the gold standard for the detection of colorectal polyps, up to a fifth of lesions may be missed on screening colonoscopy, especially non-polypoid colorectal neoplasms. Recently, many studies have reported on various endoscopic modalities that improve the detection and characterization of colorectal lesions. Newly developed modalities might be helpful to recognize colorectal lesions; however, careful observation is required to identify flat/depressed lesions as well as hidden polyps during screening and surveillance colonoscopy.

498 Training on Detection and Resection of Nonpolypoid Colorectal Neoplasms Reduces the Postcolonoscopy Colorectal Cancer Rate

498 Training on Detection and Resection of Nonpolypoid Colorectal Neoplasms Reduces the Postcolonoscopy Colorectal Cancer Rate

Suboptimal Bowel Preparation Significantly Impairs Colonoscopic Detection of Non-polypoid Colorectal Neoplasms.

It is unclear whether the quality of bowel preparation affects colonoscopic detection of non-polypoid colorectal neoplasms (NP-CRNs). To evaluate the impact of bowel-cleansing quality on detection of NP-CRNs. We performed a retrospective analysis of asymptomatic screening colonoscopy cases after standardized bowel preparation at an academic teaching hospital between June 2011 and May 2013. Primary outcome was a comparison of the adenoma detection rate (ADR) of non-polypoid morphology according to quality of bowel preparation. Secondary outcomes included detection prevalence of non-polypoid adenomas. Of the enrolled 6097 screening examinations, the preparation quality was rated as adequate (excellent or good) in 5224 (85.7%), fair in 615 (10.1%), and poor in 258 (4.2%) patients. The prevalence of NP-CRNs was 40.5% (1962/4847) of all CRNs. The overall ADR of non-polypoid morphology was 12.3% (747/6097) of all colonoscopies, but it significantly differed among participating endoscopists (all P<0.05). The ADR of non-polypoid morphology was significantly lower with fair- or poor-quality preparation, versus adequate-quality preparation (adjusted odds ratio [aOR] 0.55, 95% confidence interval [CI] 0.41-0.75; aOR 0.49, 95% CI 0.30-0.79, respectively). Poor-quality preparation was also associated with impaired detection of polypoid, proximal colon, and sub-centimeter adenomas (all P<0.05). Suboptimal (fair or poor) bowel preparation significantly impairs colonoscopic detection of NP-CRNs. Given that the prevalence of NP-CRNs is substantial in our average-risk screening cohort, ongoing efforts to improve the preparation quality are practically valuable in increasing the detection of NP-CRNs, thereby improving the efficacy of screening colonoscopies.

Non-polypoid colorectal neoplasms: Classification, therapy and follow-up.

In the last years, an increasing interest has been raised on non-polypoid colorectal tumors (NPT) and in particular on large flat neoplastic lesions beyond 10 mm tending to grow laterally, called laterally spreading tumors (LST). LSTs and large sessile polyps have a greater frequency of high-grade dysplasia and local invasiveness as compared to pedunculated lesions of the same size and usually represent a technical challenge for the endoscopist in terms of either diagnosis and resection. According to the Paris classification, NPTs are distinguished in slightly elevated (0-IIa, less than 2.5 mm), flat (0-IIb) or slightly depressed (0-IIc). NPTs are usually flat or slightly elevated and tend to spread laterally while in case of depressed lesions, cell proliferation growth progresses in depth in the colonic wall, thus leading to an increased risk of submucosal invasion (SMI) even for smaller neoplasms. NPTs may be frequently missed by inexperienced endoscopists, thus a careful training and precise assessment of all suspected mucosal areas should be performed. Chromoendoscopy or, if possible, narrow-band imaging technique should be considered for the estimation of SMI risk of NPTs, and the characterization of pit pattern and vascular pattern may be useful to predict the risk of SMI and, therefore, to guide the therapeutic decision. Lesions suitable to endoscopic resection are those confined to the mucosa (or superficial layer of submucosa in selected cases) whereas deeper invasion makes endoscopic therapy infeasible. Endoscopic mucosal resection (EMR, piecemeal for LSTs > 20 mm, en bloc for smaller neoplasms) remains the first-line therapy for NPTs, whereas endoscopic submucosal dissection in high-volume centers or surgery should be considered for large LSTs for which en bloc resection is mandatory and cannot be achieved by means of EMR. After piecemeal EMR, follow-up colonoscopy should be performed at 3 mo to assess resection completeness. In case of en bloc resection, surveillance colonoscopy should be scheduled at 3 years for adenomatous lesions ≥ 1 cm, or in presence of villous features or high-grade dysplasia patients (regardless of the size), while less intensive surveillance (colonoscopy at 5-10 years) is needed in case of single (or two) NPT < 1 cm presenting tubular features or low-grade dysplasia at histology.

Clinical experience of large colorectal laterally spreading tumor in a regional hospital: 2-year results

Summary Background Nonpolypoid colorectal neoplasm has been widely recognized in the past few years. Among nonpolypoid colorectal neoplasms, laterally spreading tumor (LST) is a unique and distinct category in that the tumor grows horizontally with a size >1 cm. It may be easily overlooked during colonoscopy. If the size of the colorectal LST is >2 cm, achieving definite management is also another concerning issue. The aim of this study was to improve our understanding of LST by reviewing its clinical manifestations. Methods All the large colorectal LSTs that were diagnosed and managed at our hospital in the past 2 years were reviewed. Basic demographic data were recorded. LSTs were divided into granular (G) and nongranular types (NG), then further subdivided into nodular mixed and homogeneous types for the G group and flat elevated and pseudodepressed types for the NG group. Results A total of 28 LST in 28 patients were enrolled, with males being more predominant than females (male/female: 18/10). Mean age of the patients and mean size of the LST were 62.6 ± 9.75 years and 3.4 ± 1.257 cm, respectively. Concerning morphology, 14 were diagnosed as NG and 14 as G group. The rate of malignant change was 28.6% (8/28). Twenty-three of our patients received endoscopic treatment (5 for endoscopic piecemeal mucosal resection 18 for endoscopic submucosal dissection) and five for laparoscopy-assisted colectomy. The cost and length of admission analysis between the endoscopic and operation treatment groups showed significant cost reduction (endoscopy/operation: NTD 28172/82516, p p Conclusion Although long-term outcome comparison was lacking, endoscopic treatment should be considered firstly for colorectal LST under the consideration of shorter hospitalization. Most of our analyses between the G and NG groups were statistically insignificant, which is likely to be due to the small population base.

Continuing Medical Education Questions: July 2013

If you wish to receive credit for this activity, please refer to the Web site:http://acgjournalcme.gi.org/. Article Title: Tracking the Molecular Features of Nonpolypoid Colorectal Neoplasms: A Systematic Review and Meta-Analysis

Tracking the Molecular Features of Nonpolypoid Colorectal Neoplasms: A Systematic Review and Meta-Analysis

Nonpolypoid colorectal neoplasms (NP-CRNs) are proposed as a major contributor to the occurrence of interval cancers, but their underlying biology remains controversial. We conducted a systematic review and meta-analysis to clarify the major biological events in NP-CRNs. We systematically searched for studies examining molecular characteristics of NP-CRNs. We performed random effect meta-analyses. We measured the heterogeneity among studies using I(2) and possible publication bias using funnel plots. Fifty-three studies on KRAS, APC, or BRAF mutations, microsatellite instability (MSI), CpG island methylator phenotype (CIMP), or DNA promoter hypermethylation were included. We observed less KRAS mutations (summary odds ratio (OR) 0.30, confidence interval (CI)=0.19-0.46, I(2)=77.4%, CI=70.1-82.9) and APC mutations (summary OR 0.42, CI=0.24-0.72, I(2)=22.6%, CI=0.0-66.7) in NP-CRNs vs. protruded CRNs, whereas BRAF mutations were more frequent (summary OR 2.20, CI=1.01-4.81, I(2)=0%, CI=0-70.8), albeit all with large heterogeneity. Less KRAS mutations were especially found in NP-CRNs subtypes: depressed CRNs (summary OR 0.12, CI=0.05-0.29, I(2)=0%, CI=0-67.6), non-granular lateral spreading tumors (LSTs-NG) (summary OR 0.61, CI=0.37-1.0, I(2)=0%, CI=0-74.6), and early nonpolypoid carcinomas (summary OR 0.11, CI=0.06-0.19, I(2)=0%, CI=0-58.3). MSI frequency was similar in NP-CRNs and protruded CRNs (summary OR 0.99, CI=0.21-4.71, I(2)=70.3%, CI=38.4-85.7). Data for promoter hypermethylation and CIMP were inconsistent, precluding meaningful conclusions. This meta-analysis provides indications that NP-CRNs are molecularly different from protruded CRNs. In particular, some subtypes of NP-CRNs, the depressed and LST-NG, are featured by less KRAS mutations than polypoid CRNs. Prospective, multicenter studies are needed to clarify the molecular pathways underlying nonpolypoid colorectal carcinogenesis and potential implications for surveillance intervals.

Tu1427 Endoscopic Treatment Strategy for Laterally Spreading Colorectal Tumor Based on the Clinicopathological Differences Between Granular-Type and Nongranular-Type

Laterally spreading tumors (LSTs) are nonpolypoid colorectal neoplasms. LST is subclassified into granular-type (LST-G) and nongranular-type (LST-NG). We previously reported endoscopic and histopathological differences between LST-G and LST-NG (Uraoka GUT 2006). The present study aimed to define more accurately the clinicopathological differences between LST-G and LST-NG, and also to clarify the indications for endoscopic submucosal dissection (ESD), which allows en-bloc resection of the lesions.