A step-by-step guide to approaching colon polyps.

Colorectal cancer (CRC) is considered one of the most prevalent cancers among Iranian men and women (1). Colorectal polyps, known as precursors of CRCs, are of great importance. Surveillance, locating, and removal of colorectal polyps make them the most modifiable factor apart from other genetic and environmental factors leading to CRCs. Colorectal polyps are defined as outpouchings from superficial and deep layers of mucosa of the colonic wall. They are classified as adenomas, serrated polyps, hyperplastic polyps, and hamartomas based on histological evaluation. Submucosal invasion precludes the possibility of endoscopic resection and should be ruled out via colonoscopic evaluation (2). Knowing this significance, the present study aims to present a brief review on classification, probability of endoscopic resection, complications of endoscopic polypectomy, as well as proper surveillance after polypectomy.

[Risk factors analysis and prediction model construction of submucosal deep infiltration of early colorectal tumor].

Objective: To investigate the risk factors for the development of deep infiltration in early colorectal tumors (ECT) and to construct a prediction model to predict the development of deep infiltration in patients with ECT. Methods: The clinicopathological data of ECT patients who underwent endoscopic treatment or surgical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences from August 2010 to December 2020 were retrospectively analyzed. The independent risk factors were analyzed by multifactorial regression analysis, and the prediction models were constructed and validated by nomogram. Results: Among the 717 ECT patients, 590 patients were divided in the within superficial infiltration 1 (SM1) group (infiltration depth within SM1) and 127 patients in the exceeding SM1 group (infiltration depth more than SM1). There were no statistically significant differences in gender, age, and lesion location between the two groups (P>0.05). The statistically significant differences were observed in tumor morphological staging, preoperative endoscopic assessment performance, vascular tumor emboli and nerve infiltration, and degree of tumor differentiation (P<0.05). Multivariate regression analysis showed that only erosion or rupture (OR=4.028, 95% CI: 1.468, 11.050, P=0.007), localized depression (OR=3.105, 95% CI: 1.584, 6.088, P=0.001), infiltrative JNET staging (OR=5.622, 95% CI: 3.029, 10.434, P<0.001), and infiltrative Pit pattern (OR=2.722, 95% CI: 1.347, 5.702, P=0.006) were independent risk factors for the development of deep submucosal infiltration in ECT. Nomogram was constructed with the included independent risk factors, and the nomogram was well distinguished and calibrated in predicting the occurrence of deep submucosal infiltration in ECT, with a C-index and area under the curve of 0.920 (95% CI: 0.811, 0.929). Conclusion: The nomogram prediction model constructed based on only erosion or rupture, local depression, infiltrative JNET typing, and infiltrative Pit pattern has a good predictive efficacy in the occurrence of deep submucosal infiltration in ECT.

Endoscopic features help to identify the histopathological patterns of colorectal polyps in Cronkhite-Canada syndrome.

OBJECTIVES: Cronkhite-Canada syndrome (CCS) is a rare nonhereditary gastrointestinal hamartomatous polyposis syndrome with a high risk of colorectal cancerogenesis. It is challenging to discriminate adenomas from nonneoplastic colorectal polyps macroscopically. This study aimed to explore the endoscopic features of different histopathological patterns of colorectal polyps in CCS. METHODS: Sixty-seven lesions from 23 CCS patients were prospectively biopsied or resected during the colonoscopic examination for histopathological analysis. The Fisher's exact test and multivariate logistical analysis were conducted to reveal the predictive endoscopic features of CCS polyps with low-grade dysplasia (LGD) and adenomas. RESULTS: There were seven (10.4%) adenomas, 20 (29.9%) CCS-LGD, and 40 (59.7%) nonneoplastic CCS polyps. Polyps were large (>20 mm) in none of the adenomas, 30.0% of CCS-LGD polyps, and 2.5% of nonneoplastic CCS polyps (P < 0.001). The color of the polyps was whitish for 71.4% of adenomas, 10.0% of CCS-LGD polyps, and 15.0% of nonneoplastic CCS polyps (P = 0.004). Pedunculated polyps were detected in 42.9% of adenomas, 45.0% of CCS-LGD polyps, and 5.0% of nonneoplastic CCS polyps (P < 0.001). The proportions of types IV and VI in the Kudo classification were 42.9%, 95.0%, and 35.0% in adenomatous, CCS-LGD, and nonneoplastic CCS polyps, respectively (P = 0.002). The endoscopic activity was in remission for 71.4% of adenomas, 5.0% of CCS-LGD polyps, and 10.0% of nonneoplastic CCS polyps (P < 0.001). CONCLUSION: Endoscopic features, including the size, color, sessility, Kudo's pit pattern classification of polyps, and endoscopic activity, help identify the histopathological patterns of colorectal polyps in CCS.

Do surface morphology and pit pattern have a role in predicting cancer for colon polyps in North America?

BACKGROUND: The surface morphology of colorectal polyps is well correlated with submucosal invasion in Eastern Countries but not in North America. We aimed to investigate associations between the Paris classification, surface morphology, and Kudo pit pattern to submucosal invasion in advanced endoscopic resection techniques. METHODS: We retrospectively analyzed prospectively collected data of consecutive advanced endoscopic procedures conducted by a single surgeon between August 2017 and October 2018. The data included patients' demographics, the endoscopic finding of polyps (Paris, Kudo, and surface morphology), and pathology results. RESULTS: The study consisted of 138 lesions, and the mean age was 67 ± 10 years. The most common polyp locations were cecum (n = 41, 30%) followed by ascending colon (n = 28, 20%), and sigmoid colon (n = 18, 13%).The median polyp size was 30 mm (25-40). The en-bloc resection rate was 96%, and 11 (8%) polyps had adenocarcinoma with submucosal invasion. Nine patients (6.5%) had late bleeding, and 3 (2.2%) perforation occurred. Polyps with pit pattern of Kudo IV (n = 4, 36.4%) and Kudo V (n = 6, 54.5%) were associated with submucosal invasion. CONCLUSIONS: Surface morphology and pit pattern can predict submucosal invasion in the North American patient population. Polyp morphology may aid polyp selection for advanced endoscopic interventions.

Risk factors analysis and prediction model construction of submucosal deep infiltration of early colorectal tumor / 中华肿瘤杂志

Objective: To investigate the risk factors for the development of deep infiltration in early colorectal tumors (ECT) and to construct a prediction model to predict the development of deep infiltration in patients with ECT. Methods: The clinicopathological data of ECT patients who underwent endoscopic treatment or surgical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences from August 2010 to December 2020 were retrospectively analyzed. The independent risk factors were analyzed by multifactorial regression analysis, and the prediction models were constructed and validated by nomogram. Results: Among the 717 ECT patients, 590 patients were divided in the within superficial infiltration 1 (SM1) group (infiltration depth within SM1) and 127 patients in the exceeding SM1 group (infiltration depth more than SM1). There were no statistically significant differences in gender, age, and lesion location between the two groups (P>0.05). The statistically significant differences were observed in tumor morphological staging, preoperative endoscopic assessment performance, vascular tumor emboli and nerve infiltration, and degree of tumor differentiation (P<0.05). Multivariate regression analysis showed that only erosion or rupture (OR=4.028, 95% CI: 1.468, 11.050, P=0.007), localized depression (OR=3.105, 95% CI: 1.584, 6.088, P=0.001), infiltrative JNET staging (OR=5.622, 95% CI: 3.029, 10.434, P<0.001), and infiltrative Pit pattern (OR=2.722, 95% CI: 1.347, 5.702, P=0.006) were independent risk factors for the development of deep submucosal infiltration in ECT. Nomogram was constructed with the included independent risk factors, and the nomogram was well distinguished and calibrated in predicting the occurrence of deep submucosal infiltration in ECT, with a C-index and area under the curve of 0.920 (95% CI: 0.811, 0.929). Conclusion: The nomogram prediction model constructed based on only erosion or rupture, local depression, infiltrative JNET typing, and infiltrative Pit pattern has a good predictive efficacy in the occurrence of deep submucosal infiltration in ECT.

Endoscopic Predictors of Neoplastic Lesions in Inflammatory Bowel Diseases Patients Undergoing Chromoendoscopy.

Dye-based chromoendoscopy (DCE) with targeted biopsies is recommended for surveillance of patients with long-standing inflammatory bowel diseases (IBD), but endoscopic features that predict dysplasia are not fully clarified. We here aimed at identifying predictive factors of dysplastic/neoplastic lesions in IBD patients undergoing DCE. Two-hundred-and-nineteen patients were consecutively and prospectively enrolled from October 2019 to March 2022. One-hundred-and-forty-five out of 219 patients underwent DCE, and 148 lesions were detected in 79/145 (54%) patients. Thirty-nine lesions (26%) were dysplastic and one of them contained a CRC. Among these lesions, 7 (17.9%) had Kudo pit pattern I-II and 32 (82.1%) had a neoplastic pit pattern (Kudo III-IV). Multivariate analysis showed that neoplastic lesions Kudo III-IV (OR: 5.8, 95% CI: 2.3−14.6; p = 0.0002), lesion's size (OR 1.16, 95% CI: 1.06−1.26; p = 0.0009), and polypoid lesions according to Paris Classification (OR 7.4, 95% CI: 2.7−20.2; p = 0.0001) were independent predictors of dysplasia. A cut-off of lesion's size > 7 mm was identified as the best predictor of dysplasia. Among such features, Kudo pit pattern III-IV had the highest sensitivity and specificity to predict dysplasia (79% and 80%, respectively). Lesions with all three endoscopic features had a sensitivity of 90% and specificity of 100% to predict dysplasia. In contrast, non-polypoid lesions were inversely associated with dysplasia (OR 0.13, 95% CI: 0.05−0.36; p = 0.0001). These findings indicate that, in IBD patients, DCE-evidenced polypoid lesions with Kudo pit pattern III-IV and size > 7 mm are frequently dysplastic.

Diagnostic performance of endoscopic classifications for neoplastic lesions in patients with ulcerative colitis: A retrospective case-control study.

BACKGROUND: It is unclear whether the Japan Narrow-Band Imaging Expert Team (JNET) classification and pit pattern classification are applicable for diagnosing neoplastic lesions in patients with ulcerative colitis (UC). AIM: To clarify the diagnostic performance of these classifications for neoplastic lesions in patients with UC. METHODS: This study was conducted as a single-center, retrospective case-control study. Twenty-one lesions in 19 patients with UC-associated neoplasms (UCAN) and 23 lesions in 22 UC patients with sporadic neoplasms (SN), evaluated by magnifying image-enhanced endoscopy, were retrospectively and separately assessed by six endoscopists (three experts, three non-experts), using the JNET and pit pattern classifications. The results were compared with the pathological diagnoses to evaluate the diagnostic performance. Inter- and intra-observer agreements were calculated. RESULTS: In this study, JNET type 2A and pit pattern type III/IV were used as indicators of low-grade dysplasia, JNET type 2B and pit pattern type VI low irregularity were used as indicators of high-grade dysplasia to shallow submucosal invasive carcinoma, JNET type 3 and pit pattern type VI high irregularity/VN were used as indicators of deep submucosal invasive carcinoma. In the UCAN group, JNET type 2A and pit pattern type III/IV had a low positive predictive value (PPV; 50.0% and 40.0%, respectively); however, they had a high negative predictive value (NPV; 94.7% and 100%, respectively). Conversely, in the SN group, JNET type 2A and pit pattern type III/IV had a high PPV (100% for both) but a low NPV (63.6% and 77.8%, respectively). In both groups, JNET type 3 and pit pattern type VI-high irregularity/VN showed high specificity. The inter-observer agreement of JNET classification and pit pattern classification for UCAN among experts were 0.401 and 0.364, in the same manner for SN, 0.666 and 0.597, respectively. The intra-observer agreements of JNET classification and pit pattern classification for UCAN among experts were 0.387, 0.454, for SN, 0.803 and 0.567, respectively. CONCLUSION: The accuracy of endoscopic diagnosis using both classifications was lower for UCAN than for SN. Endoscopic diagnosis of UCAN tended to be underestimated compared with the pathological results.

Combined endocytoscopy with pit pattern diagnosis in ulcerative colitis-associated neoplasia: Pilot study.

OBJECTIVES: Ulcerative colitis-associated neoplasias (UCAN) are often flat with an indistinct boundary from surrounding tissues, which makes differentiating UCAN from non-neoplasias difficult. Pit pattern (PIT) has been reported as one of the most effective indicators to identify UCAN. However, regenerated mucosa is also often diagnosed as a neoplastic PIT. Endocytoscopy (EC) allows visualization of cell nuclei. The aim of this retrospective study was to demonstrate the diagnostic ability of combined EC irregularly-formed nuclei with PIT (EC-IN-PIT) diagnosis to identify UCAN. METHODS: This study involved patients with ulcerative colitis whose lesions were observed by EC. Each lesion was diagnosed by two independent expert endoscopists, using two types of diagnostic strategies: PIT alone and EC-IN-PIT. We evaluated and compared the diagnostic abilities of PIT alone and EC-IN-PIT. We also examined the difference in the diagnostic abilities of an EC-IN-PIT diagnosis according to endoscopic inflammation severity. RESULTS: We analyzed 103 lesions from 62 patients; 23 lesions were UCAN and 80 were non-neoplastic. EC-IN-PIT diagnosis had a significantly higher specificity and accuracy compared with PIT alone: 84% versus 58% (P < 0.001), and 88% versus 67% (P < 0.01), respectively. The specificity and accuracy were significantly higher for Mayo endoscopic score (MES) 0-1 than MES 2-3: 93% versus 68% (P < 0.001) and 95% versus 74% (P < 0.001), respectively. CONCLUSIONS: Our novel EC-IN-PIT strategy had a better diagnostic ability than PIT alone to predict UCAN from suspected and initially detected lesions using conventional colonoscopy. UMIN clinical trial (UMIN000040698).

Indications and outcomes of endoscopic resection for non-pedunculated colorectal lesions: A narrative review.

In the last years, endoscopic techniques gained a crucial role in the treatment of colorectal flat lesions. At the same time, the importance of a reliable assessment of such lesions to predict the malignancy and the depth of invasion of the colonic wall emerged. The current unsolved dilemma about the endoscopic excision techniques concerns the necessity of a reliable submucosal invasive cancer assessment system that can stratify the risk of the post-procedural need for surgery. Accordingly, this narrative literature review aims to compare the available diagnostic strategies in predicting malignancy and to give a guide about the best techniques to employ. We performed a literature search using electronic databases (MEDLINE/PubMed, EMBASE, and Cochrane Library). We collected all articles about endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) registering the outcomes. Moreover, we analyzed all meta-analyses comparing EMR vs ESD outcomes for colorectal sessile or non-polypoid lesions of any size, preoperatively estimated as non-invasive. Seven meta-analysis studies, mainly Eastern, were included in the analysis comparing 124 studies and overall 22954 patients who underwent EMR and ESD procedures. Of these, eighty-two were retrospective, twenty-four perspective, nine case-control, and six cohorts, while three were randomized clinical trials. A total of 18118 EMR and 10379 ESD were completed for a whole of 28497 colorectal sessile or non-polypoid lesions > 5-10 mm in size. In conclusion, it is crucial to enhance the preoperative diagnostic workup, especially in deciding the most suitable endoscopic method for radical resection of flat colorectal lesions at risk of underlying malignancy. Additionally, the ESD necessitates further improvement because of the excessively time-consuming as well as the intraprocedural technical hindrances and related complications. We found a higher rate of en bloc resections and R0 for ESD than EMR for non-pedunculated colorectal lesions. Nevertheless, despite the lower local recurrence rates, ESD had greater perforation rates and needed lengthier procedural times. The prevailing risk for additional surgery in ESD rather than EMR for complications or oncologic reasons is still uncertain.

Is barium enema examination negligible for the management of colorectal cancer? Comparison with conventional colonoscopy and magnifying colonoscopy.

PURPOSE: The aim of this investigation was to evaluate the clinical value of barium enema (BE) examination for the management of colorectal epithelial neoplasms. METHODS: We reviewed the colonoscopy records at our institution from 2014 to 2019 and identified cases of endoscopically or surgically resected colorectal epithelial neoplasms evaluated by BE, conventional colonoscopy, magnifying narrow-band imaging colonoscopy (M-NBI), and magnifying chromoendoscopy (MCE). The yield of each modality for the diagnosis of massively submucosal invasive (mSM) colorectal cancer was evaluated by a receiver-operating characteristic analysis including the area under the curve (AUC). RESULTS: We analyzed the records of 105 patients (17 adenomas, 53 high-grade dysplasias (HGDs), and 35 cancers). Smooth surface, irregularity in depression, and eccentric deformity on the profile view with BE were observed more frequently in mSM cancers than adenomas/HGDs/slightly submucosal invasive cancers (p < 0.01). The AUC of BE was 0.8355, the value of which was not different from the other three modalities (conventional colonoscopy 0.7678; M-NBI 0.7835; MCE 0.8376). Although the specificity, PPV, and accuracy of BE were lower than those of M-NBI and MCE, the sensitivity and NPV of BE were the highest among the four types of examinations. CONCLUSION: BE is still available and may serve as a supplementary modality for the diagnosis of mSM cancers.

Accuracy and inter-observer agreement of the nice and kudo classifications of superficial colonic lesions: a comparative study.

PURPOSE: For superficial colonic lesions, the NICE and Kudo classifications are used in the in vivo prediction of histology and as guide to therapy. The NICE system derives information from unmagnified NBI endoscopic images. The Kudo one necessitates a magnification, but, as this tool is not commonly available, it is applied also to characterize unmagnified pictures to compare their diagnostic performances. METHODS: We conducted a prospective comparison of the NICE versus the Kudo classification for the differential diagnosis of colonic polyps taking histology as the gold standard. The inter-observer agreement for both classifications among 11 colonoscopists was also evaluated. Short unmagnified NBI videoclips of 64 colonic polyps were sent twice to the participants. In the first round, they classified the lesions according to the NICE classification; 4 months later, the same videos were assessed with the Kudo system. The diagnosis provided by the participants was grouped in non-neoplastic, non-invasive neoplasia, invasive neoplasia. RESULTS: Overall, the diagnostic accuracy was 82% (95%CI: 79-85) with the NICE system and 81% (95%CI: 78-84) with the Kudo one (ρ = 0.78). The accuracy of the NICE classification for non-neoplastic lesions was greater compared with the Kudo's (ρ = 0.03). Sensitivity sub-analyses revealed a higher ability of the NICE in distinguishing between neoplastic vs. non-neoplastic lesions (ρ = 0.01). The overall inter-rater agreement did not differ when the classifications were compared. CONCLUSION: The NICE and the Kudo classifications might be considered comparable. Our data could allow the use of the NBI Kudo classification even in those centers where magnification is not available.

A forward-viewing radial-array echoendoscope is useful for diagnosing the depth of colorectal neoplasia invasion.

BACKGROUND: It is important to accurately diagnose the depth of colorectal neoplasia invasion. We aimed to evaluate the usefulness of a new forward-viewing radial-array echoendoscope (FRE), relative to the pit pattern method. METHODS: In this prospective study, the invasion depth of suspected early-stage carcinoma was diagnosed using the pit pattern and FRE methods. The diagnoses were classified as T1a (submucosal invasion distance < 1,000 µm) or shallower and T1b (≥ 1,000 µm) or deeper. Pathological diagnoses were used to compare the diagnostic capabilities of the two methods. RESULTS: The final analyses included 110 lesions. The FRE was successfully inserted to the lesion in all cases. There were no significant differences between the two methods regarding the correct prediction rate (79.1% vs. 75.5%, P = 0.57), accuracy (81.3% vs. 79.0%, P = 0.68), specificity (81.3% vs. 70.8%, P = 0.135), positive predictive value (65.0% vs. 60.4%, P = 0.649), negative predictive value (91.0% vs. 98.1%, P = 0.108), or frequency of unevaluable cases (2.7% vs. 4.5%, P = 0.471). The correct prediction rate was calculated by adding the number of unevaluable cases to the denominator of accuracy. Relative to the pit pattern method, the FRE method offered significantly higher sensitivity for predicting T1b or deeper invasion (81.3% vs. 97.0%, P = 0.048). The pit pattern method had significantly poorer accuracy for large lesions (> 36 mm) than for smaller lesions (≤ 36 mm). In contrast, the accuracy of the FRE method did not differ significantly with lesion size. When using the FRE method, no cases were unevaluable because of attenuation. The FRE method provided correct diagnoses in 2 of 3 cases that were unevaluable using the pit pattern method. CONCLUSIONS: The pit pattern and FRE methods offered similar diagnostic performance for invasion depth. Furthermore, the FRE method may be used to correctly diagnose cases that are unevaluable using the pit pattern method.

Diagnostic efficacy of the Japan Narrow-band-imaging Expert Team and Pit pattern classifications for colorectal lesions: A meta-analysis.

BACKGROUND: Pit pattern classification using magnifying chromoendoscopy is the established method for diagnosing colorectal lesions. The Japan Narrow-band-imaging (NBI) Expert Team (JNET) classification is a novel NBI magnifying endoscopic classification that focuses on the vessel, and surface patterns. AIM: To determine the diagnostic efficacy of each category of the JNET and Pit pattern classifications for colorectal lesions. METHODS: A systematic literature search was performed using PubMed, Embase, the Cochrane Library, and Web of Science databases. The pooled sensitivity, specificity, diagnostic odds ratio, and area under the summary receiver operating characteristic curve of each category of the JNET and Pit pattern classifications were calculated. RESULTS: A total of 19227 colorectal lesions in 31 studies were included. The diagnostic performance of the JNET classification was equivalent to the Pit pattern classification in each corresponding category. The pooled sensitivity, specificity, and area under the curve (AUC) for each category of the JNET classification were as follows: 0.73 (95%CI: 0.55-0.85), 0.99 (95%CI: 0.97-1.00), and 0.97 (95%CI: 0.95-0.98), respectively, for Type 1; 0.88 (95%CI: 0.78-0.94), 0.72 (95%CI: 0.64-0.79), and 0.84 (95%CI: 0.81-0.87), respectively, for Type 2A; 0.56 (95%CI: 0.47-0.64), 0.91 (95%CI: 0.79-0.96), and 0.72 (95%CI: 0.68-0.76), respectively, for Type 2B; 0.51 (95%CI: 0.42-0.61), 1.00 (95%CI: 1.00-1.00), and 0.90 (95%CI: 0.87-0.93), respectively, for Type 3. CONCLUSION: This meta-analysis suggests that the diagnostic efficacy of the JNET classification may be equivalent to that of the Pit pattern classification. However, due to its simpler and clearer clinical application, the JNET classification should be promoted for the classification of colorectal lesions, and to guide the treatment strategy.

ESD and Pit Pattern Diagnosis: Lessons from a Japanese Endoscopist Working in the United States.

Endoscopic submucosal dissection (ESD) was developed in 2000s to overcome the limitations of endoscopic mucosal resection (EMR), especially to accomplish en-bloc resection, and it has been accepted worldwide in the past decades. Many ESD devices and diagnosis modalities are currently available, which include pit pattern and narrow band imaging (NBI) diagnoses to evaluate the depth of the tumor preoperatively with sensitivities of 70 to 90%. Depending on the Japanese colorectal guideline, the intramucosal cancer and shallow invasion of the submucosal layer are the main good indications of ESD; however, the ESD practices between Japan and Western countries still vary, including pathologic definition of cancer, tumor/node/metastasis classification, and handling of ESD specimen. In the United States, despite the large demand for treatment of colorectal neoplasm, pit pattern and magnified NBI diagnoses are not widely accepted yet, and piecemeal EMR is still the major method in most of the institutions. Moreover, the specific guideline of ESD is also not available yet. More new technologies are being developed other than conventional ESD methods in Eastern and Western countries, and ESD is now expected to change in the next generation. It is recommended that not only gastroenterologists but also colorectal surgeons have appropriate knowledge of colorectal lesions and their management to ensure current treatments is applied to patients.

[Endoscopic features and clinical correlation analysis of 24 patients with Cronkhite-Canada syndrome].

Objective: To clarify the endoscopic changes prior to corticosteroid therapy in Cronkhite-Canada syndrome (CCS) patients and to explore the correlation between endoscopic features and clinical characteristics. Methods: A total of 24 CCS patients who were hospitalized in Peking Union Medical College Hospital from January 1999 to June 2019 and underwent gastroscopy and colonoscopy before corticosteroid therapy were retrospectively enrolled. The endoscopic images were re-interpreted. The demographic characteristics, clinical manifestations, laboratory tests and histopathological data were collected and analyzed. Results: Of all 24 patients, 15 (62.5%) were male and 9(37.5%) were female, with an average age of (59±10) years and disease course of 6 (1~36) months. Based on the endoscopic findings, the percentages of stomach, colon, duodenum, rectum and terminal ileum involvement were 100%, 100%, 95.7%, 66.7% and 50.0% respectively. Gastric involvement was more severe in the lower part of the body and the antrum of the stomach, while the cardia and the fundus were spared in 5 (20.8%) cases. Colonic involvement was more severe in the right colon. No patient showed remarkable esophageal involvement. The typical appearance under endoscopy were diffuse mucosal hyperemia and edema with polyps or nodular changes. The lesions may have mulberry-like or imbricate changes in severe cases. Lymphatic dilation in the duodenum was found in 47.8% patients. Most of the polyps were pedunculated or sub-pedunculated, with occasionally seen sessile polyps in the colon. The pit patterns of the 12 resected colon polyps in 11 patients could be classified as Kudo type Ⅲ(S), Ⅲ(L), Ⅳ and Ⅴ(I), among which 2 tubular adenomas had the Kudo type Ⅲ(L). Other resected polyps were hyperplastic polyps or CCS polyps. The disease duration prior to diagnosis was positively correlated with the maximum diameter of colon polyps (r=0.625, P=0.006). Serum albumin levels in patients with whole stomach involvement were significantly lower than those in patients with cardia spared [(29±8) g/L vs (37±5) g/L, P=0.034]. Conclusions: The typical initial endoscopic finding of CCS is multiple polyps or nodular changes on the background of diffuse hyperemia and edema lining the gastric, duodenal and colonic mucosa. Lymphatic dilatation in the duodenum could also be found. Some endoscopic features are correlated to clinical characteristics.

Efficacy of linked colour imaging in magnifying chromoendoscopy with crystal violet staining: a pilot study.

PURPOSE: Diagnosis of the depth of invasion is crucial in the endoscopic management of early colorectal cancer. Image-enhanced endoscopy (IEE) is a method for easily evaluating the depth of invasion. Linked colour imaging (LCI) is an IEE method that enables clearer identification of neoplastic lesions and mucosal inflammation. The aim of this experimental study was to explore the efficacy of LCI in vessel and pit pattern recognition when used in magnifying chromoendoscopy with crystal violet staining for superficial colorectal neoplasms. METHODS: This was an experimental study. Colour difference (CD) values between the surrounding mucosa and vessels and pits were measured on white light (WLI), blue laser (BLI), and LCI images. The CD values of 10 neoplastic lesions were calculated and compared between WLI and the other techniques. RESULTS: The CD value was 9.8 (interquartile range, 7.3-12.4) for WLI, 9.7 (6.7-13.4) for LCI, and 6.8 (5.1-9.3) for BLI. The CD value was statistically different between WLI and BLI but not between WLI and LCI. With regard to vessel description, the CD value was 7.5 (4.0-11.0) for WLI, 15.6 (11.6-23.9) for LCI, and 23.3 (15.8-30.4) for BLI. CONCLUSIONS: LCI provides more diagnostic information than other light modes. Further, it is superior to the other techniques in terms of vessel visibility and is comparable to them in terms of pit recognition. These unique features of LCI may lead to its use as an alternative to WLI and BLI for pit and vessel pattern evaluation in the future.

Clinical usefulness of magnifying colonoscopy for the diagnosis of ulcerative colitis-associated neoplasia.

BACKGROUND AND AIM: The aim of this investigation was to evaluate the efficacy of Japanese magnifying colonoscopic classifications for ulcerative colitis-associated neoplasia (UCAN). METHODS: We reviewed the colonoscopy records from 2011 to 2018 at our institutions and identified cases of endoscopically or surgically resected UCAN observed by magnifying narrow-band imaging (NBI) endoscopy and magnifying chromoendoscopy. Association between magnifying endoscopic classification and histopathological findings was investigated retrospectively. Japan NBI expert team (JNET) classification and pit pattern classification were applied. RESULTS: There were 17 patients who had a diagnosis of UCAN. Tumors of types 2A, 2B and 3 by JNET classification correlated with the histopathological findings of low-grade dysplasia (LGD)/high-grade dysplasia (HGD), HGD, and massively submucosal invasive (mSM) carcinoma, respectively. Tumors of types III/IV, VI low irregularity, and VI high irregularity/VN by pit pattern classification were correlated with the histopathological findings of LGD/HGD, HGD, and mSM carcinoma, respectively. CONCLUSIONS: Japan NBI expert team classification and pit pattern classification may be predictive of the histological diagnosis and invasion depth of UCAN. This needs to be investigated prospectively in a large cohort or in a randomized clinical trial.

Integrated Analysis of the Endoscopic, Pathological and Molecular Characteristics of Colorectal Tumorigenesis.

BACKGROUND: Colorectal cancers (CRCs) develop through the accumulation of genetic and epigenetic alterations of oncogenes and tumor suppressor genes. In addition to the well-characterized adenoma-carcinoma sequence, the serrated neoplasia pathway is now recognized as an alternative pathway for CRC development. SUMMARY: Through analysis of the colonoscopic, pathological, and molecular features of colorectal tumors, we identified a novel microsurface structure characteristic of serrated lesions. The Type II-Open (Type II-O) pit pattern is highly specific to sessile serrated adenoma/polyps (SSA/Ps), and Type-II-O-positive tumors frequently exhibit v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation and 5'-C-phosphate-G-3' (CpG) island hypermethylation. By screening DNA methylation associated with the development of serrated lesions, we detected methylation of secreted protein acidic and rich in cysteine (SPARC)-related modular calcium binding 1 (SMOC1) in traditional serrated adenomas (TSAs). Epigenetic silencing of SMOC1 is prevalent among TSAs but it is rarely observed in SSA/Ps, which suggests SMOC1 could be a useful diagnostic marker of serrated lesions. We also searched for epigenetic alterations associated with the growth pattern of colorectal tumors and found that methylation of neurotensin receptor 1 is associated with lateral and non-invasive tumor growth. Key Message: Through the summarized studies, we have been able to identify novel morphological and molecular features that could contribute to a better understanding of colorectal tumors and to improved clinical diagnosis.

Surface microstructures are associated with mutational intratumoral heterogeneity in colorectal tumors.

BACKGROUND: Recent studies revealed that colorectal tumors are composed of genetically diverse subclones. We aimed to clarify whether the surface microstructures of colorectal tumors are associated with genetic intratumoral heterogeneity (ITH). METHODS: The surface microstructures (pit patterns) of colorectal tumors were observed using magnifying endoscopy, and biopsy specimens were obtained from respective areas when tumors exhibited multiple pit patterns. A total of 711 specimens from 477 colorectal tumors were analyzed for BRAF, KRAS and TP53 mutations using pyrosequencing and direct sequencing. A panel of cancer-related genes was analyzed through targeted sequencing in 7 tumors. RESULTS: Colorectal tumors with multiple pit patterns exhibited more advanced pit patterns and higher frequencies of KRAS and/or TP53 mutations than tumors with a single pit pattern. In tumors with multiple pit patterns, mutations were observed as public (common to all areas) or private (specific to certain areas), and private KRAS and/or TP53 mutations were often variable and unrelated to the pit pattern grade. Notably, invasive CRCs frequently exhibited public TP53 mutations, even in adenomatous areas, which is indicative of their early malignant potential. Targeted sequencing revealed additional public and private mutations in tumors with multiple pit patterns, indicating their single clonal origin. CONCLUSIONS: Our results suggest intratumoral pit pattern variation does not simply reflect the process of colorectal tumor evolution, but instead represents genetically diverse subclones, and this diversity may be associated with malignant potential.

Endoscopic analysis of colorectal serrated lesions with cancer.

Serrated lesions, including hyperplastic polyps (HPs), traditional serrated adenomas (TSAs) and sessile serrated adenomas/polyps (SSA/Ps), are important contributors to colorectal carcinogenesis. The aim of the present study was to analyze the potential of conventional endoscopy and advanced endoscopic imaging techniques to delineate the characteristic features of serrated lesions with cancer. The present study was a retrospective analysis of the data of 168 patients who had undergone colonoscopy, and a total of 228 serrated lesions (77 HPs, 58 TSAs, 84 SSA/Ps, 9 SSA/P plus TSAs) have been identified in these patients. A cancer component was identified in 2.6% of HPs, 13.8% of TSAs and 10.7% of SSA/Ps, but none of SSA/P plus TSAs. Compared with the lesions without cancer, the lesions with cancer exhibited a larger size (HP, TSA and SSA/P), a reddish appearance (SSA/P), a two-tier raised appearance (HP and SSA/P), a central depression (HP, TSA and SSA/P), the type V pit pattern (HP, TSA and SSA/P), and/or the type III capillary pattern (TSA and SSA/P). Deep invasion was identified in 50.0% of HPs, 12.5% of TSAs and 55.6% of SSA/Ps with cancer. The Ki-67 proliferative zone was distributed diffusely within the area of the cancer, but partially within the non-cancer area of HPs, TSAs and SSA/Ps. The lesion types were also analyzed on the basis of mucin phenotype. The present study suggested that a detailed endoscopic analysis of serrated lesions with cancer is useful for delineating characteristic features, and the analysis aids treatment selection.