A novel artificial intelligence-assisted "vascular healing" diagnosis for prediction of future clinical relapse in patients with ulcerative colitis: a prospective cohort study (with video).

BACKGROUND AND AIMS: Image-enhanced endoscopy has attracted attention as a method for detecting inflammation and predicting outcomes in patients with ulcerative colitis (UC); however, the procedure requires specialist endoscopists. Artificial intelligence (AI)-assisted image-enhanced endoscopy may help nonexperts provide objective accurate predictions with the use of optical imaging. We aimed to develop a novel AI-based system using 8853 images from 167 patients with UC to diagnose "vascular-healing" and establish the role of AI-based vascular-healing for predicting the outcomes of patients with UC. METHODS: This open-label prospective cohort study analyzed data for 104 patients with UC in clinical remission. Endoscopists performed colonoscopy using the AI system, which identified the target mucosa as AI-based vascular-active or vascular-healing. Mayo endoscopic subscore (MES), AI outputs, and histologic assessment were recorded for 6 colorectal segments from each patient. Patients were followed up for 12 months. Clinical relapse was defined as a partial Mayo score >2 RESULTS: The clinical relapse rate was significantly higher in the AI-based vascular-active group (23.9% [16/67]) compared with the AI-based vascular-healing group (3.0% [1/33)]; P = .01). In a subanalysis predicting clinical relapse in patients with MES ≤1, the area under the receiver operating characteristic curve for the combination of complete endoscopic remission and vascular healing (0.70) was increased compared with that for complete endoscopic remission alone (0.65). CONCLUSIONS: AI-based vascular-healing diagnosis system may potentially be used to provide more confidence to physicians to accurately identify patients in remission of UC who would likely relapse rather than remain stable.

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.

Whole slide image-based prediction of lymph node metastasis in T1 colorectal cancer using unsupervised artificial intelligence.

OBJECTIVES: Lymph node metastasis (LNM) prediction for T1 colorectal cancer (CRC) is critical for determining the need for surgery after endoscopic resection because LNM occurs in 10%. We aimed to develop a novel artificial intelligence (AI) system using whole slide images (WSIs) to predict LNM. METHODS: We conducted a retrospective single center study. To train and test the AI model, we included LNM status-confirmed T1 and T2 CRC between April 2001 and October 2021. These lesions were divided into two cohorts: training (T1 and T2) and testing (T1). WSIs were cropped into small patches and clustered by unsupervised K-means. The percentage of patches belonging to each cluster was calculated from each WSI. Each cluster's percentage, sex, and tumor location were extracted and learned using the random forest algorithm. We calculated the areas under the receiver operating characteristic curves (AUCs) to identify the LNM and the rate of over-surgery of the AI model and the guidelines. RESULTS: The training cohort contained 217 T1 and 268 T2 CRCs, while 100 T1 cases (LNM-positivity 15%) were the test cohort. The AUC of the AI system for the test cohort was 0.74 (95% confidence interval [CI] 0.58-0.86), and 0.52 (95% CI 0.50-0.55) using the guidelines criteria (P = 0.0028). This AI model could reduce the 21% of over-surgery compared to the guidelines. CONCLUSION: We developed a pathologist-independent predictive model for LNM in T1 CRC using WSI for determination of the need for surgery after endoscopic resection. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN000046992, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000053590).

Evaluation in real-time use of artificial intelligence during colonoscopy to predict relapse of ulcerative colitis: a prospective study.

BACKGROUND AND AIMS: The use of artificial intelligence (AI) during colonoscopy is attracting attention as an endoscopist-independent tool to predict histologic disease activity of ulcerative colitis (UC). However, no study has evaluated the real-time use of AI to directly predict clinical relapse of UC. Hence, it is unclear whether the real-time use of AI during colonoscopy helps clinicians make real-time decisions regarding treatment interventions for patients with UC. This study aimed to establish the role of real-time AI in stratifying the relapse risk of patients with UC in clinical remission. METHODS: This open-label, prospective, cohort study was conducted in a referral center. The cohort comprised 145 consecutive patients with UC in clinical remission who underwent AI-assisted colonoscopy with a contact-microscopy function. We classified patients into either the Healing group or Active group based on the AI outputs during colonoscopy. The primary outcome measure was clinical relapse of UC (defined as a partial Mayo score >2) during 12 months of follow-up after colonoscopy. RESULTS: Overall, 135 patients completed the 12-month follow-up after AI-assisted colonoscopy. AI-assisted colonoscopy classified 61 patients as the Healing group and 74 as the Active group. The relapse rate was significantly higher in the AI-Active group (28.4% [21/74]; 95% confidence interval, 18.5%-40.1%) than in the AI-Healing group (4.9% [3/61]; 95% confidence interval, 1.0%-13.7%; P < .001). CONCLUSIONS: Real-time use of AI predicts the risk of clinical relapse in patients with UC in clinical remission, which helps clinicians make real-time decisions regarding treatment interventions. (Clinical trial registration number: UMIN000036650.).

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).

Beyond complete endoscopic healing: Goblet appearance using an endocytoscope to predict future sustained clinical remission in ulcerative colitis.

OBJECTIVES: Complete endoscopic healing, defined as Mayo endoscopic score (MES) = 0, is an optimal target in the treatment of ulcerative colitis (UC). However, some patients with MES = 0 show clinical relapse within 12 months. Histologic goblet mucin depletion has emerged as a predictor of clinical relapse in patients with MES = 0. We observed goblet depletion in vivo using an endocytoscope, and analyzed the association between goblet appearance and future prognosis in UC patients. METHODS: In this retrospective cohort study, all enrolled UC patients had MES = 0 and confirmed clinical remission between October 2016 and March 2020. We classified the patients into two groups according to the goblet appearance status: preserved-goblet and depleted-goblet groups. We followed the patients until March 2021 and evaluated the difference in cumulative clinical relapse rates between the two groups. RESULTS: We identified 125 patients with MES = 0 as the study subjects. Five patients were subsequently excluded. Thus, we analyzed the data for 120 patients, of whom 39 were classified as the preserved-goblet group and 81 as the depleted-goblet group. The patients were followed-up for a median of 549 days. During follow-up, the depleted-goblet group had a significantly higher cumulative clinical relapse rate than the preserved-goblet group (19% [15/81] vs. 5% [2/39], respectively; P = 0.02). CONCLUSIONS: Observing goblet appearance in vivo allowed us to better predict the future prognosis of UC patients with MES = 0. This approach may assist clinicians with onsite decision-making regarding treatment interventions without a biopsy.

Development of a computer-aided detection system for colonoscopy and a publicly accessible large colonoscopy video database (with video).

BACKGROUND AND AIMS: Artificial intelligence (AI)-assisted polyp detection systems for colonoscopic use are currently attracting attention because they may reduce the possibility of missed adenomas. However, few systems have the necessary regulatory approval for use in clinical practice. We aimed to develop an AI-assisted polyp detection system and to validate its performance using a large colonoscopy video database designed to be publicly accessible. METHODS: To develop the deep learning-based AI system, 56,668 independent colonoscopy images were obtained from 5 centers for use as training images. To validate the trained AI system, consecutive colonoscopy videos taken at a university hospital between October 2018 and January 2019 were searched to construct a database containing polyps with unbiased variance. All images were annotated by endoscopists according to the presence or absence of polyps and the polyps' locations with bounding boxes. RESULTS: A total of 1405 videos acquired during the study period were identified for the validation database, 797 of which contained at least 1 polyp. Of these, 100 videos containing 100 independent polyps and 13 videos negative for polyps were randomly extracted, resulting in 152,560 frames (49,799 positive frames and 102,761 negative frames) for the database. The AI showed 90.5% sensitivity and 93.7% specificity for frame-based analysis. The per-polyp sensitivities for all, diminutive, protruded, and flat polyps were 98.0%, 98.3%, 98.5%, and 97.0%, respectively. CONCLUSIONS: Our trained AI system was validated with a new large publicly accessible colonoscopy database and could identify colorectal lesions with high sensitivity and specificity. (Clinical trial registration number: UMIN 000037064.).

Current status and future perspective on artificial intelligence for lower endoscopy.

The global incidence and mortality rate of colorectal cancer remains high. Colonoscopy is regarded as the gold standard examination for detecting and eradicating neoplastic lesions. However, there are some uncertainties in colonoscopy practice that are related to limitations in human performance. First, approximately one-fourth of colorectal neoplasms are missed on a single colonoscopy. Second, it is still difficult for non-experts to perform adequately regarding optical biopsy. Third, recording of some quality indicators (e.g. cecal intubation, bowel preparation, and withdrawal speed) which are related to adenoma detection rate, is sometimes incomplete. With recent improvements in machine learning techniques and advances in computer performance, artificial intelligence-assisted computer-aided diagnosis is being increasingly utilized by endoscopists. In particular, the emergence of deep-learning, data-driven machine learning techniques have made the development of computer-aided systems easier than that of conventional machine learning techniques, the former currently being considered the standard artificial intelligence engine of computer-aided diagnosis by colonoscopy. To date, computer-aided detection systems seem to have improved the rate of detection of neoplasms. Additionally, computer-aided characterization systems may have the potential to improve diagnostic accuracy in real-time clinical practice. Furthermore, some artificial intelligence-assisted systems that aim to improve the quality of colonoscopy have been reported. The implementation of computer-aided system clinical practice may provide additional benefits such as helping in educational poorly performing endoscopists and supporting real-time clinical decision-making. In this review, we have focused on computer-aided diagnosis during colonoscopy reported by gastroenterologists and discussed its status, limitations, and future prospects.

Artificial Intelligence-assisted System Improves Endoscopic Identification of Colorectal Neoplasms.

BACKGROUND & AIMS: Precise optical diagnosis of colorectal polyps could improve the cost-effectiveness of colonoscopy and reduce polypectomy-related complications. However, it is difficult for community-based non-experts to obtain sufficient diagnostic performance. Artificial intelligence-based systems have been developed to analyze endoscopic images; they identify neoplasms with high accuracy and low interobserver variation. We performed a multi-center study to determine the diagnostic accuracy of EndoBRAIN, an artificial intelligence-based system that analyzes cell nuclei, crypt structure, and microvessels in endoscopic images, in identification of colon neoplasms. METHODS: The EndoBRAIN system was initially trained using 69,142 endocytoscopic images, taken at 520-fold magnification, from patients with colorectal polyps who underwent endoscopy at 5 academic centers in Japan from October 2017 through March 2018. We performed a retrospective comparative analysis of the diagnostic performance of EndoBRAIN vs that of 30 endoscopists (20 trainees and 10 experts); the endoscopists assessed images from 100 cases produced via white-light microscopy, endocytoscopy with methylene blue staining, and endocytoscopy with narrow-band imaging. EndoBRAIN was used to assess endocytoscopic, but not white-light, images. The primary outcome was the accuracy of EndoBrain in distinguishing neoplasms from non-neoplasms, compared with that of endoscopists, using findings from pathology analysis as the reference standard. RESULTS: In analysis of stained endocytoscopic images, EndoBRAIN identified colon lesions with 96.9% sensitivity (95% CI, 95.8%-97.8%), 100% specificity (95% CI, 99.6%-100%), 98% accuracy (95% CI, 97.3%-98.6%), a 100% positive-predictive value (95% CI, 99.8%-100%), and a 94.6% negative-predictive (95% CI, 92.7%-96.1%); these values were all significantly greater than those of the endoscopy trainees and experts. In analysis of narrow-band images, EndoBRAIN distinguished neoplastic from non-neoplastic lesions with 96.9% sensitivity (95% CI, 95.8-97.8), 94.3% specificity (95% CI, 92.3-95.9), 96.0% accuracy (95% CI, 95.1-96.8), a 96.9% positive-predictive value, (95% CI, 95.8-97.8), and a 94.3% negative-predictive value (95% CI, 92.3-95.9); these values were all significantly higher than those of the endoscopy trainees, sensitivity and negative-predictive value were significantly higher but the other values are comparable to those of the experts. CONCLUSIONS: EndoBRAIN accurately differentiated neoplastic from non-neoplastic lesions in stained endocytoscopic images and endocytoscopic narrow-band images, when pathology findings were used as the standard. This technology has been authorized for clinical use by the Japanese regulatory agency and should be used in endoscopic evaluation of small polyps more widespread clinical settings. UMIN clinical trial no: UMIN000028843.

Treatment policy for colonic laterally spreading tumors based on each clinicopathologic feature of 4 subtypes: actual status of pseudo-depressed type.

BACKGROUND AND AIMS: Laterally spreading tumors (LSTs) are originally classified into 4 subtypes. Pseudo-depressed nongranular types (LSTs-NG-PD) are gaining attention because of their high malignancy potential. Previous studies discussed the classification of nongranular (LST-NG) and granular types (LST-G); however, the actual condition or indication for endoscopic treatment of LSTs-NG-PD remains unclear. We aimed to compare the submucosal invasion pattern of LSTs-NG-PD with the other 3 subtypes. METHODS: A total of 22,987 colonic neoplasms including 2822 LSTs were resected endoscopically or surgically at Showa University Northern Yokohama Hospital. In these LSTs, 322 (11.4%) were submucosal invasive carcinomas. We retrospectively evaluated the clinicopathologic features of LSTs divided into 4 subtypes. In 267 LSTs resected en bloc, their submucosal invasion site was further evaluated. RESULTS: The frequency of LSTs in all colonic neoplasms was significantly higher in women (14.9%) than in men (11.0%). Rates of submucosal invasive carcinoma were .8% in the granular homogenous type (LSTs-G-H), 15.2% in the granular nodular mixed type (LSTs-G-M), 8.0% in the nongranular flat elevated type (LSTs-NG-F), and 42.5% in LSTs-NG-PD. Tumor size was associated with submucosal invasion rate in LSTs-NG-F and LSTs-NG-PD (P < .001). The multifocal invasion rate of LSTs-NG-PD (46.9%) was significantly higher than that of LSTs-G-M (7.9%) or LSTs-NG-F (11.8%). In LSTs-NG-PD, the invasion was significantly deeper (≥1000 µm) if observed in 1 site. CONCLUSIONS: For LSTs-G-M and LSTs-NG-F that may have invaded the submucosa, en bloc resection could be considered. Considering that LSTs-NG-PD had a higher submucosal invasion rate, more multifocal invasive nature, and deeper invasion tendency, regardless if invasion was only observed in 1 site, than LSTs-NG-F, we should endoscopically distinguish LSTs-NG-PD from LSTs-NG-F and strictly adopt en bloc resection by endoscopic submucosal dissection or surgery for LSTs-NG-PD. (Clinical trial registration number: UMIN 000020261.).

Endocytoscopic intramucosal capillary network changes and crypt architecture abnormalities can predict relapse in patients with an ulcerative colitis Mayo endoscopic score of 1.

OBJECTIVES: Recent studies have suggested the necessity of therapeutic intervention for patients with ulcerative colitis at high risk of clinical relapse with a Mayo endoscopic score (MES) of 1. The aim of this retrospective cohort study was to demonstrate the impact of intramucosal capillary network changes and crypt architecture abnormalities to stratify the risk of relapse in patients with an MES of 1. METHODS: All included patients had an MES of ≤1 and confirmed sustained clinical remission between October 2016 and April 2019. We classified patients with an MES of 1 as "intramucosal capillary/crypt (ICC)-active" or "ICC-inactive" using endocytoscopic evaluation. We followed patients until October 2019 or until relapse; the main outcome measure was the difference in clinical relapse-free rates between ICC-active and ICC-inactive patients with an MES of 1. RESULTS: We included 224 patients and analyzed data for 218 (82 ICC-active and 54 ICC-active with an MES of 1 and 82 with an MES of 0). During follow-up, among the patients with an MES of 1, 30.5% (95% confidence interval 20.8-41.6; 25/82) of the patients relapsed in the ICC-active group and 5.6% (95% confidence interval 1.2-15.4; 3/54) of the patients relapsed in the ICC-inactive group. The ICC-inactive group had a significantly higher clinical relapse-free rate compared with the ICC-active group (P < 0.01). CONCLUSIONS: In vivo intramucosal capillary network and crypt architecture patterns stratified the risk of clinical relapse in patients with an MES of 1 (UMIN 000032580; UMIN 000036359).

Artificial intelligence may help in predicting the need for additional surgery after endoscopic resection of T1 colorectal cancer.

BACKGROUND AND STUDY AIMS: Decisions concerning additional surgery after endoscopic resection of T1 colorectal cancer (CRC) are difficult because preoperative prediction of lymph node metastasis (LNM) is problematic. We investigated whether artificial intelligence can predict LNM presence, thus minimizing the need for additional surgery. PATIENTS AND METHODS: Data on 690 consecutive patients with T1 CRCs that were surgically resected in 2001 - 2016 were retrospectively analyzed. We divided patients into two groups according to date: data from 590 patients were used for machine learning for the artificial intelligence model, and the remaining 100 patients were included for model validation. The artificial intelligence model analyzed 45 clinicopathological factors and then predicted positivity or negativity for LNM. Operative specimens were used as the gold standard for the presence of LNM. The artificial intelligence model was validated by calculating the sensitivity, specificity, and accuracy for predicting LNM, and comparing these data with those of the American, European, and Japanese guidelines. RESULTS: Sensitivity was 100 % (95 % confidence interval [CI] 72 % to 100 %) in all models. Specificity of the artificial intelligence model and the American, European, and Japanese guidelines was 66 % (95 %CI 56 % to 76 %), 44 % (95 %CI 34 % to 55 %), 0 % (95 %CI 0 % to 3 %), and 0 % (95 %CI 0 % to 3 %), respectively; and accuracy was 69 % (95 %CI 59 % to 78 %), 49 % (95 %CI 39 % to 59 %), 9 % (95 %CI 4 % to 16 %), and 9 % (95 %CI 4 % - 16 %), respectively. The rates of unnecessary additional surgery attributable to misdiagnosing LNM-negative patients as having LNM were: 77 % (95 %CI 62 % to 89 %) for the artificial intelligence model, and 85 % (95 %CI 73 % to 93 %; P < 0.001), 91 % (95 %CI 84 % to 96 %; P < 0.001), and 91 % (95 %CI 84 % to 96 %; P < 0.001) for the American, European, and Japanese guidelines, respectively. CONCLUSIONS: Compared with current guidelines, artificial intelligence significantly reduced unnecessary additional surgery after endoscopic resection of T1 CRC without missing LNM positivity.

Efficacy of ledipasvir/sofosbuvir with or without ribavirin for 12 weeks in genotype 1b HCV patients previously treated with a nonstructural protein 5A inhibitor-containing regimen.

AIM: The therapeutic benefit of adding ribavirin (RBV) to 12 weeks of ledipasvir/sofosbuvir (LDV/SOF) for patients who experienced failure of a previous nonstructural protein (NS) 5A inhibitor-containing regimen is unclear. METHODS: A total of 29 genotype 1b HCV patients who had failed prior daclatasvir (DCV) plus asunaprevir (ASV) treatment were retreated for 12 weeks of LDV/SOF, with or without RBV. Antiviral efficacy and predictive factors associating with a sustained virological response at 24 weeks (SVR24) were evaluated retrospectively. RESULTS: SVR24 was achieved in 67% (10/15) of patients who received LDV/SOF with, and 64% (9/14) without, RBV. The SVR24 rates were 80% in patients with, and 58% without, mild fibrosis (FIB-4 < 3.25). The SVR24 rate was lower with unfavorable IL28B rs8099917 SNP genotypes; specifically, the TT, TG and GG had SVR24 rates of 78%, 50% and 40%. The SVR24 rate was lower with a poor response to prior DCV plus ASV, where relapse, viral breakthrough and no response had SVR24 rates 71%, 58% and 0%. The SVR24 rate was lower with the number of NS5A resistance-associated substitutions (RAS), where 2, 3, 4 and 5 RAS had SVR24 rates of 78%, 67%, 50% and 0%. A patient with an NS5A-P32 deletion, which shows resistance to next-generation NS5A inhibitors, was retreated with LDV/SOF with RBV and achieved SVR24. CONCLUSIONS: The addition of RBV to 12 weeks of LDV/SOF has little therapeutic benefit when retreating patients in whom a prior NS5A inhibitor-containing regimen had failed.

Management and risk factor of stenosis after endoscopic submucosal dissection for colorectal neoplasms.

BACKGROUND AND AIM: Although endoscopic submucosal dissection (ESD) enables en bloc removal of large colorectal neoplasms, the incidence of stenosis after ESD and its risk factors have not been well described. This study aimed to determine the risk factors of stenosis and verify the surveillance and treatment of stenosis. METHODS: This retrospective study included 822 patients, with a total of 912 consecutive colorectal lesions, who underwent ESD from September 2003 to May 2015. The main outcome measures were incidence of stenosis and its relationship with the clinicopathologic factors in surveillance. RESULTS: Surveillance endoscopy was performed 6 months after ESD. Four of the 822 patients (0.49%) developed stenosis and required unanticipated endoscopy. The other 908 cases in 818 patients showed no symptoms or only slight abdominal discomfort (that was controlled with medication) and did not require any dilation or steroid therapies. Post-ESD stenosis was observed in 11.1% (2/18) of patients with circumferential resection between ≥90% and <100% and in 50% (2/4) of patients with circumferential resection of 100%. Among the 50 cases with a circumferential mucosal defect ≥75%, a circumferential mucosal defect ≥90% was a significant risk factor (P = .005). Four patients with stenosis were treated successfully by endoscopic dilation. CONCLUSIONS: Circumferential mucosal defect of more than 90% is a significant risk factor for stenosis after colorectal ESD. Surveillance endoscopy 6 months after ESD is recommended to assess for development of stenosis. Defects smaller than 90% do not require close endoscopic follow-up or prophylactic measures for prevention of post-ESD stenosis. (UMIN clinical trial registration number: UMIN000015754.).

Accuracy of diagnosing invasive colorectal cancer using computer-aided endocytoscopy.

Background and study aims Invasive cancer carries the risk of metastasis, and therefore, the ability to distinguish between invasive cancerous lesions and less-aggressive lesions is important. We evaluated a computer-aided diagnosis system that uses ultra-high (approximately × 400) magnification endocytoscopy (EC-CAD). Patients and methods We generated an image database from a consecutive series of 5843 endocytoscopy images of 375 lesions. For construction of a diagnostic algorithm, 5543 endocytoscopy images from 238 lesions were randomly extracted from the database for machine learning. We applied the obtained algorithm to 200 endocytoscopy images and calculated test characteristics for the diagnosis of invasive cancer. We defined a high-confidence diagnosis as having a ≥ 90 % probability of being correct. Results Of the 200 test images, 188 (94.0 %) were assessable with the EC-CAD system. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were 89.4 %, 98.9 %, 94.1 %, 98.8 %, and 90.1 %, respectively. High-confidence diagnosis had a sensitivity, specificity, accuracy, PPV, and NPV of 98.1 %, 100 %, 99.3 %, 100 %, and 98.8 %, respectively. Conclusion: EC-CAD may be a useful tool in diagnosing invasive colorectal cancer.

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.

Prediction of oral absorption of low-solubility drugs by using rat simulated gastrointestinal fluids: the importance of regional differences in membrane permeability and solubility.

PURPOSE: This study aimed to develop a novel approach for predicting the oral absorption of low-solubility drugs by considering regional differences in solubility and permeability within the gastrointestinal (GI) tract. METHODS: Simulated GI fluids were prepared to reflect rat in vivo bile acid and phospholipid concentrations in the upper and lower small intestine. The saturated solubility and permeability of griseofulvin (GF) and albendazole (AZ), a drug with low aqueous solubility, were measured using these simulated fluids, and fraction absorbed (Fa) at time t after oral administration was calculated. RESULTS: The saturated solubility of GF and AZ, a drug with low aqueous solubility, differed considerably between the simulated GI fluids. Large regional differences in drugs concentration were also observed following oral administration in vivo. The predicted Fa values using solubility and permeability data of the simulated GI fluid were found to correspond closely to the in vivo data. CONCLUSION: These results indicated the importance of evaluating regional differences in drug solubility and permeability in order to predict oral absorption of low-solubility drugs accurately. The new methodology developed in the present study could be useful for new oral drug development.

Differentiation grade as a risk factor for lymph node metastasis in T1 colorectal cancer.

Objectives: Japanese guidelines include high-grade (poorly differentiated) tumors as a risk factor for lymph node metastasis (LNM) in T1 colorectal cancer (CRC). However, whether the grading is based on the least or most predominant component when the lesion consists of two or more levels of differentiation varies among institutions. This study aimed to investigate which method is optimal for assessing the risk of LNM in T1 CRC. Methods: We retrospectively evaluated 971 consecutive patients with T1 CRC who underwent initial or additional surgical resection from 2001 to 2021 at our institution. Tumor grading was divided into low-grade (well- to moderately differentiated) and high-grade based on the least or predominant differentiation analyses. We investigated the correlations between LNM and these two grading analyses. Results: LNM was present in 9.8% of patients. High-grade tumors, as determined by least differentiation analysis, accounted for 17.0%, compared to 0.8% identified by predominant differentiation analysis. A significant association with LNM was noted for the least differentiation method (p < 0.05), while no such association was found for predominant differentiation (p = 0.18). In multivariate logistic regression, grading based on least differentiation was an independent predictor of LNM (p = 0.04, odds ratio 1.68, 95% confidence interval 1.00-2.83). Sensitivity and specificity for detecting LNM were 27.4% and 84.1% for least differentiation, and 2.1% and 99.3% for predominant differentiation, respectively. Conclusions: Tumor grading via least differentiation analysis proved to be a more reliable measure for assessing LNM risk in T1 CRC compared to grading by predominant differentiation.