Impact of computer-aided characterization for diagnosis of colorectal lesions, including sessile serrated lesions: Multireader, multicase study.

OBJECTIVES: Computer-aided characterization (CADx) may be used to implement optical biopsy strategies into colonoscopy practice; however, its impact on endoscopic diagnosis remains unknown. We aimed to evaluate the additional diagnostic value of CADx when used by endoscopists for assessing colorectal polyps. METHODS: This was a single-center, multicase, multireader, image-reading study using randomly extracted images of pathologically confirmed polyps resected between July 2021 and January 2022. Approved CADx that could predict two-tier classification (neoplastic or nonneoplastic) by analyzing narrow-band images of the polyps was used to obtain a CADx diagnosis. Participating endoscopists determined if the polyps were neoplastic or not and noted their confidence level using a computer-based, image-reading test. The test was conducted twice with a 4-week interval: the first test was conducted without CADx prediction and the second test with CADx prediction. Diagnostic performances for neoplasms were calculated using the pathological diagnosis as reference and performances with and without CADx prediction were compared. RESULTS: Five hundred polyps were randomly extracted from 385 patients and diagnosed by 14 endoscopists (including seven experts). The sensitivity for neoplasia was significantly improved by referring to CADx (89.4% vs. 95.6%). CADx also had incremental effects on the negative predictive value (69.3% vs. 84.3%), overall accuracy (87.2% vs. 91.8%), and high-confidence diagnosis rate (77.4% vs. 85.8%). However, there was no significant difference in specificity (80.1% vs. 78.9%). CONCLUSIONS: Computer-aided characterization has added diagnostic value for differentiating colorectal neoplasms and may improve the high-confidence diagnosis rate.

Practical problems of measuring depth of submucosal invasion in T1 colorectal carcinomas.

PURPOSE: Submucosal invasion depth (SID) in colorectal carcinoma (CRC) is an important factor in estimating risk of lymph node metastasis, but can be difficult to measure, leading to inadequate or over-extensive treatment. Here, we aimed to clarify the practical aspects of measuring SID in T1 CRC. METHODS: We investigated 568 T1 CRCs that were resected surgically at our hospital from April 2001 to December 2013, and relationships between SID and clinicopathological factors, including the means of measurement, lesion morphology, and lymph node metastasis. RESULTS: Of these 568 lesions, the SID was ≥1000 µm in 508 lesions. SIDs for lesions measured from the surface layer were all ≥1000 µm. Although lesions with SIDs ≥1000 µm were associated with significantly higher levels of unfavorable histologic types and lymphovascular infiltration than shallower lesions, a depth of ≥1000 µm was not a significant risk factor for lymph node metastasis (LNM) (6.7 vs. 9.8 %; P = 0.64), and no lesions for which the sole pathological factor was SID ≥1000 µm had lymph node metastasis. Protruded lesions showed deeper SIDs than other types. CONCLUSIONS: Although we found several problems of measuring SID in this study, we also found, surprisingly, that SID is not a risk factor for lymph node metastasis, and its measurement is not needed to estimate the risk of lymph node metastasis.

Management of T1 colorectal cancers after endoscopic treatment based on the risk stratification of lymph node metastasis.

BACKGROUND AND AIM: Recent advances in endoscopic technology have allowed many T1 colorectal carcinomas to be resected endoscopically with negative margins. However, the criteria for curative endoscopic resection remain unclear. We aimed to identify risk factors for nodal metastasis in T1 carcinoma patients and hence establish the indication for additional surgery with lymph node dissection. METHODS: Initial or additional surgery with nodal dissection was performed in 653 T1 carcinoma cases. Clinicopathological factors were retrospectively analyzed with respect to nodal metastasis. The status of the muscularis mucosae (MM grade) was defined as grade 1 (maintenance) or grade 2 (fragmentation or disappearance). The lesions were then stratified based on the risk of nodal metastasis. RESULTS: Muscularis mucosae grade was associated with nodal metastasis (P = 0.026), and no patients with MM grade 1 lesions had nodal metastasis. Significant risk factors for nodal metastasis in patients with MM grade 2 lesions were attribution of women (P = 0.006), lymphovascular infiltration (P < 0.001), tumor budding (P = 0.045), and poorly differentiated adenocarcinoma or mucinous carcinoma (P = 0.007). Nodal metastasis occurred in 1.06% of lesions without any of these pathological factors, but in 10.3% and 20.1% of lesions with at least one factor in male and female patients, respectively. There was good inter-observer agreement for MM grade evaluation, with a kappa value of 0.67. CONCLUSIONS: Stratification using MM grade, pathological factors, and patient sex provided more appropriate indication for additional surgery with lymph node dissection after endoscopic treatment for T1 colorectal carcinomas.

'Head Invasion' Is Not a Metastasis-Free Condition in Pedunculated T1 Colorectal Carcinomas Based on the Precise Histopathological Assessment.

BACKGROUND/AIM: Previous reports stated that pedunculated T1 colorectal carcinomas with 'head invasion' showed almost no nodal metastasis, requiring endoscopic treatment alone. However, clinically, some lesions develop nodal metastasis. We aimed to validate the necessity of distinguishing between 'pedunculated' and 'non-pedunculated' lesions, and also between 'head' and 'stalk' invasions. METHODS: Initial or additional surgery with lymph node dissection was performed in 76 pedunculated and 594 non-pedunculated cases. Among pedunculated lesions, the baseline was defined as the junction line between normal and neoplastic epithelium (Haggitt's level 2). The degree of invasion was classified as 'head invasion' (above the baseline) or 'stalk invasion' (beyond the baseline). Clinicopathological factors were analyzed with respect to nodal metastasis. RESULTS: Nine of 76 (11.8%) pedunculated cases and 52/594 (8.8%) non-pedunculated cases developed nodal metastasis (p = 0.40). No significant differences were found in the rate of nodal metastasis between 'head invasion' (4/30, 13.3%) and 'stalk invasion' (5/46, 10.9%). All the 4 cases with 'head invasion' had at least one pathological factor. CONCLUSIONS: 'Head invasion' was not a metastasis-free condition. Even for pedunculated T1 cancers with 'head invasion', additional surgery with lymph node dissection should be considered if these have pathological risk factors.

Endocytoscopic microvasculature evaluation is a reliable new diagnostic method for colorectal lesions (with video).

BACKGROUND: We previously reported on the efficacy of endocytoscopic classification (EC-C). However, the correlation of the endocytoscopic vascular (EC-V) pattern with diagnoses was unclear. OBJECTIVE: To assess the diagnostic accuracy of the EC-V pattern for colorectal lesions. DESIGN: Retrospective. SETTING: A university hospital. PATIENTS: Patients who underwent endocytoscopy between January 2010 and March 2013. INTERVENTION: We evaluated 198 consecutive lesions according to the EC-V pattern (EC-V1, obscure surface microvessels; EC-V2, clearly observed surface microvessels of a uniform caliber and arrangement; and EC-V3, dilated surface microvessels of a nonhomogeneous caliber or arrangement). MAIN OUTCOME MEASUREMENTS: The diagnostic accuracy for predicting hyperplastic polyps and invasive cancer were compared between the EC-V pattern and other modalities (narrow-band imaging, pit pattern, and EC-C). RESULTS: The sensitivity, specificity, and accuracy of the EC-V1 pattern for diagnosing hyperplastic polyps were 95.5%, 99.4%, and 99.0%, respectively. The sensitivity, specificity, and accuracy of the EC-V3 pattern for diagnosing invasive cancer were 74.6%, 97.2%, and 88.6%, respectively. The diagnostic accuracy of the EC-V pattern for predicting hyperplastic polyps was comparable to the other modalities. For predicting invasive cancer, the EC-V pattern was comparable to narrow-band imaging and pit pattern, although EC-C was slightly more accurate (P = .04). In the substudy, the diagnosis time by using the EC-V pattern was shorter than that with the EC-C pattern (P < .001). LIMITATIONS: A single-center, retrospective study. CONCLUSIONS: The EC-V pattern saved more time than the EC-C pattern and had a diagnostic ability comparable to that of other optical biopsy modalities.

Clinicopathological features of small T1 colorectal cancers.

BACKGROUND: Although small colorectal neoplasms (< 10 mm) are often easily resected endoscopically and are considered to have less malignant potential compared with large neoplasms (≥ 10 mm), some are invasive to the submucosa. AIM: To clarify the clinicopathological features of small T1 colorectal cancers. METHODS: Of 32025 colorectal lesions between April 2001 and March 2018, a total of 1152 T1 colorectal cancers resected endoscopically or surgically were included in this study and were divided into two groups by tumor size: a small group (< 10 mm) and a large group (≥ 10 mm). We compared clinicopathological factors including lymph node metastasis (LNM) between the two groups. RESULTS: The incidence of small T1 cancers was 10.1% (116/1152). The percentage of initial endoscopic treatment in small group was significantly higher than in large group (< 10 mm 74.1% vs ≥ 10 mm 60.2%, P < 0.01). In the surgical resection cohort (n = 798), the rate of LNM did not significantly differ between the two groups (small 12.3% vs large 10.9%, P = 0.70). In addition, there were also no significant differences between the two groups in pathological factors such as histological grade, vascular invasion, or lymphatic invasion. CONCLUSION: Because there was no significant difference in the rate of LNM between small and large T1 colorectal cancers, the requirement for additional surgical resection should be determined according to pathological findings, regardless of tumor size.

Small invasive colon cancer with adenoma observed by endocytoscopy: A case report.

BACKGROUND: Endocytoscopy is a next-generation endoscopic system that facilitates real-time histopathologic endoscopic diagnosis of colorectal lesions by virtue of its 520 × maximum magnification. CASE SUMMARY: We present the case of a 63-year-old man with sigmoid colon cancer who was regularly referred for follow-up colonoscopy after endoscopic resection of T1 rectal cancer. Colonoscopy revealed a 12 mm reddish polyp, including a depression and a flat area in the sigmoid colon. Endocytoscopic observation showed unclear gland formation and agglomeration of distorted nuclei (depression), suggesting a submucosal invasive (T1) cancer. In the flat area, slit-like smooth lumens and regular pattern of fusiform nuclei were found, suggesting an adenoma. On the basis of these endocytoscopic findings, we predicted this lesion as T1 cancer (depression) with adenoma (flat area) and performed endoscopic resection corresponding to the final histopathological diagnosis. CONCLUSION: We could perform an optical diagnosis of T1 sigmoid cancer with adenoma by using endocytoscopy before treatment.

Endocytoscopy with NBI has the potential to correctly diagnose diminutive colorectal polyps that are difficult to diagnose using conventional NBI.

Background and study aims Real-time diagnosis of colorectal polyps is needed to prevent unnecessary resection of benign polyps. The vessels in hyperplastic polyps sometimes mimic the characteristic meshed capillary network of neoplastic lesions on non-magnified narrow-band imaging (NBI). Endocytoscopy in conjunction with NBI (EC-NBI) enables more detailed vessel observation. The current study evaluated whether EC-NBI can accurately diagnose small colorectal lesions with visible vessels on non-magnified NBI. Patients and methods This retrospective study was conducted from January to December 2016. During colonoscopy, lesion images were obtained using NBI and EC-NBI. On EC-NBI, lesions were classified as having "clear," "unclear," or "invisible" blood vessel margins. All specimens were resected and pathologically examined, and the association between vessel margin findings and pathological diagnosis was assessed. The lesion surface to vessel depth was measured in clear, unclear, and invisible lesions. Results Among 114 adenomas, 108 were clear, while six were unclear. Among 36 hyperplastic polyps, eight were clear, while 28 were unclear. A micro-network (MN) pattern was seen in 106 of 114 adenomas, and four of 36 hyperplastic polyps. The sensitivity, specificity, correct diagnostic rate, and positive and negative predictive values of clear blood vessel margins or a MN pattern as an adenoma index were 98.2 %, 69.4 %, 91.3 %, 91.1 %, and 92.6 %, respectively. EC-NBI correctly diagnosed 69.4 % (25/36) of hyperplastic polyps. The lesion surface-blood vessel distance was greater in unclear versus clear lesions ( P  < 0.001), and invisible versus unclear lesions ( P  < 0.001). Conclusions EC-NBI may effectively differentiate hyperplastic polyps with visible vessels from adenomas. Blood vessel depth affects visibility.

White light-emitting contrast image capsule endoscopy for visualization of small intestine lesions: a pilot study.

BACKGROUND AND STUDY AIMS: Capsule endoscopy (CE) has become a routine means of diagnosing obscure gastrointestinal bleeding (OGIB) in the small intestine. Capsules using novel blue-enhanced white light-emitting diodes are expected to acquire clearer contrast images (CIs) of the small bowel vasculature. We conducted a pilot study to examine whether CIs facilitate visualization of small bowel erosions, ulcers, and areas of angioectasia compared with standard white light images (WLIs). PATIENTS AND METHODS: A total of 24 patients with OGIB were recruited in this study. The main outcome measure was visibility of lesions on CIs compared with WLIs. We also examined the color difference between lesions and normal mucosa (ΔE) with each imaging modality. RESULTS: Three experienced physicians retrospectively evaluated 138 images of small bowel lesions (107 erosions, or ulcers, and 31 areas of angioectasia) obtained from 24 CE examinations. The endoscopists judged that compared with WLIs, CIs afforded easier identification of erosions or ulcers in 29 of 107 cases (27.1 %), were non-inferior in 68 of 107 cases (63.6 %), and were inferior in 10 of 107 cases (9.3 %). Identification of angioectasia was judged to be easier with CIs in 15 of 31 cases (48.4 %), non-inferior in 13 of 31 cases (41.9 %), and inferior in 3 of 31 cases (9.7 %). ΔE was significantly higher for CIs than WLIs, especially for angioectasia, potentially explaining why lesions were easier to visualize. CONCLUSIONS: CIs obtained by CE appear to facilitate identification of small bowel erosions, ulcers, and areas of angioectasia compared with WLIs.

The concept of 'Semi-clean colon' using the pit pattern classification system has the potential to be acceptable in combination with a <3-year surveillance colonoscopy.

Histological features of colorectal lesions are currently evaluated via a magnifying chromoendoscopy [pit pattern (PIT) classification]. Advanced histological features are rarely observed in diminutive (≤5 mm) adenomatous polyps (DAPs). The Japanese guidelines indicate that diminutive neoplastic lesions without carcinomatous findings may be left untreated and followed up. At the present institution, DAPs with type IIIL PIT are left untreated in various cases, whereas lesions with type III, IV or V PIT are typically resected via routine colonoscopy. This retrospective study aimed to assess the management of DAPs using PIT classification. The participants of the study included patients <30 years previously referred for an initial colonoscopy, then reobserved for <3 years following the procedure. Participants were classified into three groups: Group A, Patients with type IIIL PIT DAP left untreated (semi-clean colon group); group B, patients with all neoplastic polyps, including DAPs, resected (clean colon group); and group C, patients without any adenomatous polyps (internal control group). The cumulative incidence of the index lesions (ILs) at the follow-up colonoscopy was analysed among the three groups. A total of 4,313 patients were enrolled in the study, with categorization as follows: Group A, 1,246; group B, 1,205; and group C, 1,862 patients. ILs were detected in group A, 100 (8.0%); group B, 104 (8.6%); and group C, 29 (1.6%) patients. There was no significant difference observed between groups A and B. It was verified that removing the type IIIL PIT DAPs did not decrease the incidence of ILs within a 3-year time period. Therefore, these polyps may be left untreated in combination with patient reobservation at an appropriate time interval, potentially one equal to that suggested following a polypectomy.

In vivo detection of desmoplastic reaction using endocytoscopy: A new diagnostic marker of submucosal or more extensive invasion in colorectal carcinoma.

The pathological determination of desmoplastic reaction (DR) in colorectal carcinoma is useful for predicting extensive submucosal invasion. The aim of the present study was to determine the usefulness of endocytoscopy (EC) in detecting DR. A total of 72 cases of colorectal cancer with submucosal invasion (EC classification, EC3b) were evaluated. The utility of fine granular structure (FGS) observed via EC for the prediction of the presence of DR in the most superficial tumor layers was assessed. Of the 72 lesions, 26 were positive for FGS, and the majority of these lesions (23/26, 88.5%) exhibited a DR, indicating a significant association. The overall accuracy of the identification of FGS via EC that was predictive of a DR was 87.3%. The presence of FGS detected by EC was significantly associated with the presence of a DR, suggesting the clinical usefulness of EC in planning treatment for colon cancer with submucosal invasion.

Retrospective analysis of large bowel obstruction or perforation caused by oral preparation for colonoscopy.

BACKGROUND AND STUDY AIMS: Patients undergoing bowel preparation for colonoscopy are at risk of potentially severe adverse events such as large-bowel obstruction (LBO) and perforation. These patients usually need emergency surgery and the consequences may be fatal. Little is known about the risk factors for LBO and perforation in these circumstances. We sought to establish the natural history of LBO and perforation caused by oral preparation for colonoscopy. PATIENTS AND METHODS: We retrospectively analyzed data from 20 patients with LBO or perforation associated with oral preparation for colonoscopy. All patients were treated at the Showa University Northern Yokohama Hospital (SUNYH) between April 2001 and December 2015. Drugs used for bowel preparation, age, sex, indication for colonoscopy, pathogenesis and treatment were recorded. RESULTS: Eighteen of the patients had LBO and 2 had perforation. Fourteen events occurred at SUNYH, which accounted for 0.016 % of patients who underwent bowel preparation during this period. Seventeen patients were symptomatic when the decision to undertake colonoscopy was made (including 7 who complained of constipation and 4 who complained of abdominal pain; 3e were asymptomatic). Nineteen patients ultimately required surgery, 13 within 3 days of presentation. Eleven patients ultimately required colostomy. There was no perioperative mortality in our cases. CONCLUSION: Large bowel obstruction and perforation are rare events associated with oral preparation for colonoscopy, but frequently require surgery. Exacerbation of constipation might be a risk factor for LBO or perforation. Potentially catastrophic situations can be avoided by early detection and treatment.

Comparative clinicopathological characteristics of colon and rectal T1 carcinoma.

Lymph node metastasis significantly influences the management of patients with colorectal carcinoma. It has been observed that the biology of colorectal carcinoma differs by location. The aim of the current study was to retrospectively compare the clinicopathological characteristics of patients with colon and rectal T1 carcinomas, particularly their rates of lymph node metastasis. Of the 19,864 patients who underwent endoscopic or surgical resection of colorectal neoplasms at Showa University Northern Yokohama Hospital, 557 had T1 surgically resected carcinomas, including 457 patients with colon T1 carcinomas and 100 patients with rectal T1 carcinomas. Analysed clinicopathological features included patient age, gender, tumor size, morphology, tumor budding, invasion depth, vascular invasion, histological grade, lymphatic invasion and lymph node metastasis. Rectal T1 carcinomas were significantly larger than colon T1 carcinomas (mean ± standard deviation: 23.7±13.1 mm vs. 19.9±11.0 mm, P<0.01) and were accompanied by significantly higher rates of vascular invasion (48.0% vs. 30.2%, P<0.01). Significant differences were not observed among any other clinicopathological factors. In conclusion, tumor location itself was not a risk factor for lymph node metastasis in colorectal T1 carcinomas, even though on average, rectal T1 carcinomas were larger and accompanied by a significantly higher rate of vascular invasion than colon T1 carcinomas.

Patient gender as a factor associated with lymph node metastasis in T1 colorectal cancer: A systematic review and meta-analysis.

Approximately 10% of patients with T1 colorectal cancer have lymph node metastases (LNM), requiring node dissection along with surgical resection. Patient gender was recently reported to affect the occurrence of LNM. The aim of the present study was to assess whether patient gender was predictive of LNM in T1 colorectal cancer. Public databases, including PubMed, EMBASE and the Cochrane Central Register of Controlled Trials were searched, using key terms related to 'T1 colorectal cancer' and 'lymph node'. All relevant studies reporting the adjusted odds ratio or risk ratio of LNM in relation to patient gender were included. The quality of the studies was classified according to the Quality in Prognostic Studies tool. A random-effects model was used and the quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. The initial database search identified 2,492 publications; of those, 36 studies reported unadjusted results. Of the 36 studies, 4 reported adjusted results and fulfilled the inclusion criteria for this meta-analysis: 3 studies were graded as having a moderate risk of bias, and 1 had a low risk of bias. The present meta-analysis demonstrated that female gender was associated with increased risk of LNM (risk ratio=2.45, 95% confidence interval: 1.03-3.88). The I2 statistic was 0.901, classified as very low (+OOO) and was downgraded by the risk of bias, inconsistency and publication bias. In conclusion, female gender was found to be correlated with LNM in patients with T1 colorectal cancer.

Depressed-Type Colonic Lesions and "De Novo" Cancer in Familial Adenomatous Polyposis: A Colonoscopist's Viewpoint.

Familial adenomatous polyposis (FAP) is the most common inherited polyposis syndrome. Almost all patients with FAP will develop colorectal cancer if their FAP is not identified and treated at an early stage. Although there are many reports about polypoid lesions and colorectal cancers in FAP patients, little information is available concerning depressed lesions in FAP patients. Several reports suggested that depressed-type lesions are characteristic of FAP and important in the light of their rapid growth and high malignancy. Here, we describe the occurrence of depressed-type lesions in FAP patients treated at our institution. Between April 2001 and March 2010, eight of 18 FAP patients had colorectal cancers. Depressed-type colorectal cancer was found in three patients. It should be kept in mind that depressed-type lesions occur even in FAP.

Proliferating potential and apoptosis in the development of secondary hyperparathyroidism: a study based on Ki-67 immunohistochemical staining and the terminal dUTP nick-end labeling assay.

Secondary hyperparathyroidism (SHPT) is a common complication in hemodialysis (HD) patients. SHPT progresses from initial diffuse hyperplasia (diffuse) to early nodularity (early), then to multinodular hyperplasia (nodular), and finally to a single nodule (single) consisting of uniform parenchymal cells. We analyzed the roles of proliferation and apoptosis in SHPT progression. Seventy-four parathyroid glands from 36 HD patients with SHPT, and 10 parathyroid glands from 10 non-HD patients without SHPT were used for analysis. The former were classified as diffuse (N = 17), early (N = 22), nodular (N = 20), and single (N = 15); the latter were classified as normal (N = 10). To analyze proliferating cells we used Ki-67, and to detect apoptotic cells, we used the terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP nick-end labeling (TUNEL) assay. Concerning the Ki-67 labeling index (LI), the incremental order was single, nodular, early, diffuse, and normal. Oxyphilic cells and around the central portion of each lesion were distinctly stained by Ki-67. Concerning the TUNEL LI, the incremental order was early, diffuse, nodular, single, and normal. Chief cells and around the peripheral portion of each lesion were distinctly stained by TUNEL. In the progression from early to nodular, for oxyphilic cells, the Ki-67 LI increased and the TUNEL LI decreased; for chief cells, the Ki-67 LI decreased and the TUNEL LI showed no significant change. We considered that proliferative activity increases and that the apoptosis rate decreases as SHPT progresses from diffuse to single. Moreover, the specific differences in the rate of proliferation and apoptosis between oxyphilic and chief cells might be associated with SHPT progression.

Immunohistochemical analysis of nestin and c-kit and their significance in pancreatic tumors.

The purpose of the present study was to clarify the difference of expression of two stem cell markers, nestin and c-kit, among various pancreatic epithelial tumors and evaluate their utility. Immunohistochemistry was done for 99 surgically resected pancreatic tumor specimens, including 20 ductal adenocarcinoma (DAC), two undifferentiated carcinomas (UC), 31 intraductal papillary-mucinous neoplasms (IPMN), six mucinous cystic neoplasms (MCN), five serous cystadenomas (SCA), six acinar cell carcinomas, two pancreatoblastoma (PB), eight solid-pseudopapillary neoplasms (SPN), and 19 endocrine neoplasms (EN). Nestin was widely expressed in four SPN, one PB, one SCA, sarcoma areas in two UC, one MCN, and one DAC, and an area of oncocytic component in one IPMN. Some of these SPN, SCA and sarcomatous or oncocytic components in which nestin was expressed, also coexpressed c-kit. Additionally, partial (scattered) expression of c-kit was observed in ductal elements of 16 DAC, eight IPMN, five MCN, and one UC, one SCA, and three EN. The eight c-kit-positive IPMN included four of 23 adenoma-to-border lesions and four of eight non-invasive-to-invasive carcinomas. The three EN were all carcinomas. These indicate that expression of two stem cell markers is different by tumor type, but the utility of judging direction or degree of differentiation and malignant grade on the basis of their expression status is suggested.