Development of high-quality artificial intelligence for computer-aided diagnosis in determining subtypes of colorectal cancer.

BACKGROUND AND AIM: There are no previous studies in which computer-aided diagnosis (CAD) diagnosed colorectal cancer (CRC) subtypes correctly. In this study, we developed an original CAD for the diagnosis of CRC subtypes. METHODS: Pretraining for the CAD based on ResNet was performed using ImageNet and five open histopathological pretraining image datasets (HiPreD) containing 3 million images. In addition, sparse attention was introduced to improve the CAD compared to other attention networks. One thousand and seventy-two histopathological images from 29 early CRC cases at Kyoto Prefectural University of Medicine from 2019 to 2022 were collected (857 images for training and validation, 215 images for test). All images were annotated by a qualified histopathologist for segmentation of normal mucosa, adenoma, pure well-differentiated adenocarcinoma (PWDA), and moderately/poorly differentiated adenocarcinoma (MPDA). Diagnostic ability including dice sufficient coefficient (DSC) and diagnostic accuracy were evaluated. RESULTS: Our original CAD, named Colon-seg, with the pretraining of both HiPreD and ImageNET showed a better DSC (88.4%) compared to CAD without both pretraining (76.8%). Regarding the attentional mechanism, Colon-seg with sparse attention showed a better DSC (88.4%) compared to other attentional mechanisms (dual: 79.7%, ECA: 80.7%, shuffle: 84.7%, SK: 86.9%). In addition, the DSC of Colon-seg (88.4%) was better than other types of CADs (TransUNet: 84.7%, MultiResUnet: 86.1%, Unet++: 86.7%). The diagnostic accuracy of Colon-seg for each histopathological type was 94.3% for adenoma, 91.8% for PWDA, and 92.8% for MPDA. CONCLUSION: A deep learning-based CAD for CRC subtype differentiation was developed with pretraining and fine-tuning of abundant histopathological images.

Efficacy of Glycicumarin and Isoliquiritigenin in Suppressing Colonic Peristalsis in Both an Animal Model and a Clinical Trial.

Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) show excessive peristalsis, and antispasmodic agents may be useful therapeutic agents. There are few reports on the use of Kampo medicines for the treatment of IBS-D. Shakuyakukanzoto (SKT) is a Kampo medicine that is effective against abdominal pain. We examined the relationship between SKT and intestinal peristalsis in an animal model and a prospective study. In the animal model, SKT and its components were administered from the serosal side of the colon and colonic peristalsis was evaluated using intraluminal pressure and spatiotemporal mapping before and after the administration of SKT and its components. In this clinical trial, we used abdominal ultrasonography (US) to obtain long-axis images of the sigmoid colon of 11 patients. The frequency of intestinal peristalsis was measured using US in five patients with SKT and six patients without medication after the ingestion of a test meal. The primary outcome was the frequency of peristalsis. The Clinical Trial Registry Website (Trial No. UMIN-CTR; UMIN000051547). In the animal model, peony did not suppress peristalsis frequency, but SKT (p = 0.005) and glycyrrhiza (p = 0.001) significantly suppressed peristalsis frequency compared with saline and peony. Among the glycyrrhiza components, glycycoumarin and isoliquiritigenin suppressed the peristalsis frequency compared to dimethyl sulfoxide (control) (p = 0.001, 0.01, respectively). In a clinical trial, peristalsis was significantly suppressed after oral administration in patients taking SKT (p = 0.03). Administration of SKT was found to inhibit colonic peristalsis, with glycicumarin and isoliquiritigenin being particularly relevant among its components.

Gastrointestinal Angiodysplasia in Patients with Severe Aortic Stenosis: The Endoscopic Features of Heyde's Syndrome.

INTRODUCTION: Aortic stenosis (AS) is sometimes associated with gastrointestinal bleeding, and this phenomenon is known as Heyde's syndrome. Such bleeding is most often considered to originate from gastrointestinal angiodysplasias, but the frequency and endoscopic features of such bleeding remain unclear. This study aimed to determine the frequency and endoscopic features of gastrointestinal angiodysplasia in patients with severe AS. PATIENTS AND METHODS: In this multicenter, retrospective study, we evaluated consecutive patients who underwent transcatheter aortic valve implantation (TAVI) with severe AS from May 2016 to December 2019. We extracted the data on the clinicopathological features according to the status of anemia, the proportion of patients who underwent gastrointestinal endoscopic examinations and demonstrated gastrointestinal angiodysplasia, and identified the endoscopic features associated with such patients. RESULTS: In 325 patients, the rates of moderate/severe anemia (hemoglobin < 11 g/dL) were 52%. Regarding medicine, there were no significant differences between the patients with and without moderate/severe anemia. Patients were examined by esophagogastroduodenoscopy (21%), colonoscopy (12%), and balloon-assisted enteroscopy or small bowel capsule endoscopy (1.5%). Patients with moderate/severe anemia had significantly more angiodysplasia (38.3% vs. 7.7%; p < 0.0001) and active bleeding (23.4% vs. 0%; p < 0.01). Angiodysplasia was detected in 21 patients (stomach, n = 9; small intestine, n = 5, and colon, n = 10). CONCLUSIONS: The results suggest, for the first time, that patients with severe AS who underwent TAVI and moderate/severe anemia frequently had gastrointestinal angiodysplasia and active bleeding throughout the entire gastrointestinal tract.

Standard Endoscopic Mucosal Resection vs Precutting Endoscopic Mucosal Resection Using Novel Disk-Tip Snare for Colorectal Lesions.

INTRODUCTION: SOUTEN (KANEKA Co., Tokyo, Japan) is a unique snare with a disk tip. We analyzed the efficacy of precutting endoscopic mucosal resection with SOUTEN (PEMR-S) for colorectal lesions. METHODS: We retrospectively reviewed 57 lesions of 10-30 mm treated with PEMR-S at our institution from 2017 to 2022. The indications were lesions that were difficult for standard EMR due to size, morphology, and poor elevation by injection. Various therapeutic results of PEMR-S such as en bloc resection, procedure time, and perioperative hemorrhage were analyzed, and the results of 20 lesions of 20-30 mm with PEMR-S were compared to those of lesions with standard EMR (2012-2014) using propensity score matching. Additionally, the stability of the SOUTEN disk tip was analyzed in a laboratory experiment. RESULTS: The polyp size was 16.5 ± 4.2 mm and the non-polypoid morphology rate was 80.7%. Histopathological diagnosis included 10 sessile-serrated lesions, 43 low-grade and high-grade dysplasias, and 4 T1 cancers. After matching, the en bloc resection and histopathological complete resection rates of lesions of 20-30 mm between PEMR-S and standard EMR (90.0% vs. 58.1%, p = 0.03 and 70.0% vs. 45.0%, p = 0.11). The procedure time (min) was 14.8 ± 9.7 and 9.7 ± 8.3 (p < 0.01). The en bloc resection (%) and procedure time of expert/non-expert were 89.7/85.7 (p = 0.96) and 6.1 ± 2.2/18.5 ± 7.2 (p < 0.01). The perioperative bleeding and hemostasis success rates with SOUTEN were 43.9% and 96.0%. In the experiment, the SOUTEN disk tip was fixed stably compared to other EMR snares. CONCLUSIONS: PEMR-S achieved high en bloc resection of colorectal lesions of 20-30 mm though it leaded to long procedure time.

Deoxycholic acid delays the wound healing of colonic epithelial cells via transmembrane G-protein-coupled receptor 5.

BACKGROUND AND AIM: Efficient intestinal wound healing is essential for good prognoses of ulcerative colitis (UC). Although bile acids and the transmembrane G-protein-coupled receptor (TGR) 5 have been reported to affect wound healing in intestinal epithelial cells, the detailed underlying mechanisms are unclear. Here, we investigated the role of TGR5 in wound healing in the context of colonic epithelial cells in the presence of bile acids. METHODS: The expression of TGR5 in the colonic epithelium of both a dextran sulfate sodium (DSS)-induced colitis mouse model (recovery phase), and UC patients in clinical remission, was evaluated. Young adult mouse colonic epithelial (YAMC) cells were then used to evaluate wound healing after treatment with deoxycholic acid (DCA); TGR5 was silenced in YAMC cells via shRNA-transfection, and a wound-healing assay in the presence of DCA was performed. Furthermore, we investigated the role of the activation of AKT in the context of wound healing. RESULTS: The expression of TGR5 was decreased in the colonic epithelium of both mice with DSS-induced colitis and UC patients. Additionally, DCA significantly delayed wound healing in YAMC cells but not in TGR5 silenced ones. Of note, the DCA-induced activation of AKT signaling in YAMC cells was inhibited by TGR5 silencing, and AKT inhibitors prevented the wound healing delay induced by DCA. CONCLUSIONS: Overall, we show that DCA delays wound healing in the context of colonic epithelial cells through AKT activation. These results may support the development of new therapeutic approaches for epithelial regeneration in UC.

Analysis of Texture and Color Enhancement Imaging for Improving the Visibility of Non-polypoid Colorectal Lesions.

INTRODUCTION: An endoscopic system using 5-color light-emitting diodes (LEDs) (EVIS X1; Olympus Co., Tokyo, Japan), which includes texture and color enhancement imaging (TXI), has been released. In this study, we analyzed the effects of TXI on the visibility of non-polypoid colorectal lesions and its diagnostic accuracy. METHODS: We reviewed 101 non-polypoid lesions from 26 patients observed with white light imaging (WLI), narrow band imaging (NBI), and TXI. One representative image of each mode was evaluated by 6 endoscopists using a polyp visibility score of 4 (excellent) to 1 (poor). We calculated the color difference (CD) values for each lesion in the three modes. For tumor characteristics, one representative image of TXI and NBI magnification was evaluated by 3 experts according to a NBI classification. RESULTS: The least squares means [95% confidence interval] of polyp visibility score of TXI (3.42 [3.06-3.77]) was significantly higher than that of WLI (2.85 [2.49-3.20], p < 0.001) but not that of NBI (3.33 [2.98-3.69], p = 0.258). The CD value of TXI (13.3 ± 6.3) was higher than that of WLI (9.7 ± 6.0, p < 0.001) but not that of NBI (13.1 ± 6.8, p = 0.81). For sessile serrated lesions, the CD value of TXI (11.1 ± 4.4) tended to be lower than that of NBI (12.6 ± 6.0, p = 0.07). The diagnostic accuracy and confidence level of magnification for NBI were significantly better than those for TXI (87.1 vs. 80.5%, p = 0.027, 87.5 vs. 62.7%, p < 0.001, respectively). CONCLUSION: TXI showed better visibility than WLI in terms of the endoscopist's score and CD value and may improve polyp detection.

Repeat Cold Snare Polypectomy Can Be Performed for Recurrent Benign Lesions After Cold Snare Polypectomy.

BACKGROUND AND AIMS: Recurrence after cold snare polypectomy (CSP) sometimes occurs. We assessed the feasibility of repeat CSP for recurrence after CSP. METHODS: We retrospectively reviewed recurrent lesions after CSP which were resected by repeat CSP from 2016 to 2021 in our institution and analyzed clinical outcomes of repeat CSP, comparing those of non-recurrent 454 lesions receiving standard CSP in 2016 and follow-up colonoscopy. We also analyzed the recurrent rate among cases receiving follow-up in both groups. Indication of repeat CSP was lesions diagnosed as benign tumors of ≤ 10 mm. RESULTS: We analyzed 80 lesions receiving repeat CSP. The polyp size (mean ± standard deviation: SD) was 4.1 ± 2.3 mm (range 2-10 mm). The right-sided colon and non-polypoid morphology rates were 66.3% and 43.8%, respectively. Histopathological diagnosis was 66 adenomas, 12 sessile serrated lesions (SSLs), 1 SSL with dysplasia, and 1 high-grade dysplasia. The procedure time (min, mean ± SD) of repeat CSP was 0.9 ± 0.8. Regarding the comparison of repeat CSP/ standard CSP group, the en bloc resection and histopathological complete resection rates were 78.8%/ 98.0% (p < 0.001) and 43.8%/59.6% (p = 0.007) and the rates of perioperative hemorrhage requiring endoscopic clipping were 1.3%/ 1.0% (p = 0.646). There were no postoperative hemorrhage and perforation in both groups (p = 1.0). Among lesions receiving follow-up colonoscopy, the mean recurrence rates (number, median follow-up period: interquartile) of repeat CSP and standard CSP group were 2.0% (1/50, 12 months: 12-24) versus 0.7% (3/454, 12 months: 12-24) (p = 0.862). CONCLUSIONS: Repeat CSP for benign recurrent lesions after CSP was safe and feasible.

An analysis about the function of a new artificial intelligence, CAD EYE with the lesion recognition and diagnosis for colorectal polyps in clinical practice.

OBJECTIVES: Recently, CAD EYE (Fujifilm, Tokyo, Japan), an artificial intelligence for the lesion recognition (CADe) and the optical diagnosis (CADx) of colorectal polyps, was released. We evaluated the function of CADe and CADx of CAD EYE. METHODS: In this single-center retrospective study, we examined consecutive polyps ≤ 10 mm detected from March to April 2021 to determine whether CAD EYE could recognize them live with both normal- and high-speed observation using white-light imaging (WLI) and linked-color imaging (LCI). We then examined whether the polyps were neoplastic or hyperplastic live with magnified or non-magnified blue-laser imaging (BLI-LASER) or blue-light imaging (BLI-LED) under CAD EYE, comparing the retrospective evaluations with 5 experts and 5 trainees using still images. All polyps were histopathologically examined. RESULTS: We analyzed 100 polyps (mean size 3.9 ± 2.6 mm; 55 neoplastic and 45 hyperplastic lesions) in 25 patients. Regarding CADe, the respective detection rates of CAD EYE with normal- and high-speed observation were 85.0% and 67.0% for WLI (p = 0.002) and 89.0% and 75.0% for LCI (p = 0.009). Regarding CADx for differentiating neoplastic and hyperplastic lesions, the diagnostic accuracy values of CAD EYE with non-magnified and magnified BLI-LASER/LED were 88.8% and 87.8%. Regarding magnified BLI-LASER/LED, the diagnostic accuracy value of CAD EYE was not significantly different from that of experts (92.0%, p = 0.17), but that of trainees (79.0%, p = 0.04). We also found no significant differences in CADe or CADx between LED (53 lesions) and LASER (47 lesions). CONCLUSIONS: CAD EYE was a helpful tool for CADe and CADx in clinical practice.

The efficacy of tumor characterization and tumor detectability of linked color imaging and blue laser imaging with an LED endoscope compared to a LASER endoscope.

OBJECTIVES: An endoscope with a light-emitting diode (LED) light source which has a 2-mm close-distance observation function without magnification, has been marketed, enabling linked color imaging (LCI) and blue laser imaging (BLI) for tumor detection and characterization. We analyzed the efficacy of a LED endoscope compared to a LASER endoscope. METHODS: We retrospectively reviewed 272 lesions observed using the LED endoscopic system (Fujifilm Co., Tokyo, Japan) from May 2018 to September 2019. The Japanese NBI Classification was used for tumor characterization. We analyzed the diagnostic accuracy and confidence level. Sixty-one lesions observed with both the LED and magnified LASER endoscopes were also analyzed to compare the diagnostic accuracy. Regarding the tumor detectability, we calculated color difference values (CDVs) and brightness values (BVs) of white-light imaging, BLI, and LCI modes between the two endoscopes for each tumor. RESULTS: The mean polyp size was 9.2 ± 11.3 mm. Histology showed 71 sessile serrated lesions, 193 adenoma and high-grade dysplasias, and 8 T1 cancers. The diagnostic accuracy of tumors ≥ 10 and < 10 mm was 72.0% and 92.9% (p < 0.001), respectively and the high confidence rate was 93.8%. The diagnostic accuracy of LED (77.0%) was a little higher than that of LASER without magnification (65.6%, p = 0.16) but was not inferior to that of LASER with magnification (82.0%, p = 0.50). The respective CDVs of LED and LASER endoscopes were 20.6 ± 11.2 and 21.6 ± 11.2 for LCI (p = 0.30), and the respective BVs were 210.0 ± 24.2 and 175.9 ± 21.1 (p < 0.001). CONCLUSIONS: A LED endoscope with close-distance observation improved tumor detection and characterization due to high brightness.

Effects of L-Menthol and Carbon Dioxide on the Adenoma Detection Rate during Colonoscopy: L-Menthol and Carbon Dioxide on Colonoscopy.

BACKGROUND AND AIMS: We examined the efficacy of the combined use of L-menthol spraying (L-mentholS) as an antispasmodic agent and carbon dioxide insufflation (CO2I) on the adenoma detection rate (ADR) in a prospective, single-center trial with a 2 × 2 factorial design. METHODS: We randomly assigned 611 patients scheduled to undergo colonoscopy to 4 groups: (1) the L-mentholS + CO2I (n = 153), (2) L-mentholS + air insufflation (AI; n = 156), (3) CO2I (n = 153), and (4) AI (n = 149) groups. We used 20 mL of 0.8%-L-menthol solution for the L-mentholS. The primary outcome was the difference in the ADR, and the secondary outcomes were the differences in colonic peristalsis and abdominal pain. -Results: The ADRs were not different among the groups: 1/2/3/4; 39.9%/43.6%/41.2%/51.0%. CO2I was associated with a significant decrease in the ADR (OR 0.57; 95% CI 0.35- 0.93) with a multiple logistic regression. The interaction between L-mentholS and CO2I was associated with a suppression of the decrease in the ADR. Both L-mentholS and CO2I were associated with a significant decrease in abdominal pain, and L-mentholS was associated with a significant improvement of peristalsis. CONCLUSIONS: The fact that CO2I was associated with significant decreases in the ADR was a problem. The combined use of L-mentholS and CO2I could help to suppress the decrease in the ADR.

The Comparison of Diagnostic Ability between Blue Laser/Light Imaging and Narrowband Imaging for Sessile Serrated Lesions with or without Dysplasia.

Objectives: Diagnostic ability of sessile serrated lesions (SSL) and SSL with dysplasia (SSLD) using blue laser/light imaging (BLI) has not been well examined. We analyzed the diagnostic accuracy of BLI for SSL and SSLD using several endoscopic findings compared to those of narrow band imaging (NBI). Materials and Methods: This was a subgroup analysis of prospective studies. 476 suspiciously serrated lesions of ≥2 mm on the proximal colon showing serrated change with magnified NBI or BLI in our institution between 2014 and 2021 were examined histopathologically. After propensity score matching, we evaluated the diagnostic ability of SSL and SSLD of the NBI and BLI groups regarding various endoscopic findings. For WLI findings, granule, depression, and reddish were examined for diagnosing SSLD. For NBI/BLI findings, expanded crypt opening (ECO) or thick and branched vessels (TBV) were examined for diagnosing SSL. Network vessels (NV) and white dendritic change (WDC) defined originally were examined for diagnosing SSLD. Results: Among matched 176 lesions, the sensitivity of lesions with either ECO or TBV for SSL in the NBI/BLI group was 97.5%/98.5% (p = 0.668). Those with either WDC or NV for diagnosing SSLD in the groups were 81.0%/88.9% (p = 0.667). Regarding the rates of endoscopic findings among 30 SSLD and 290 SSL, there were significant differences in WDC (66.4% vs. 8.6%, p < 0.001), NV (55.3% vs. 1.4%, p < 0.001), and either WDC or NV (86.8% vs. 9.0%, p < 0.001). Conclusions: The diagnostic ability of BLI for SSL and SSLD was not different from NBI. NV and WDC were useful for diagnosing SSLD.

Partially hydrolyzed guar gum increased colonic mucus layer in mice via succinate-mediated MUC2 production.

Colonic mucus layers protect intestinal tissues against intestinal bacteria. We investigated the effects of dietary fiber and its metabolites on mucus production in the colonic mucosa. Mice were fed a partially hydrolyzed guar gum (PHGG)-containing diet and a fiber-free diet (FFD). The colon mucus layer, fecal short-chain fatty acid (SCFA) levels, and gut microbiota were evaluated. Mucin 2 (MUC2) expression was assessed in SCFA-treated LS174T cells. The role of AKT in MUC2 production was investigated. The mucus layer in the colonic epithelium was significantly increased in the PHGG group compared with that in the FFD group. In the PHGG group, an increase in Bacteroidetes in the stool was observed, and fecal acetate, butyrate, propionate, and succinate levels were significantly increased. However, MUC2 production was significantly increased only in succinate-stimulated LS174T cells. The succinate-induced MUC2 production was associated with AKT phosphorylation. Succinate mediated the PHGG-induced increase in the colon mucus layer.

Two cases of colonic tumors observed by linked color imaging and texture and color enhancement imaging with the tablet-image comparison method.

An endoscope system using 5-color light-emitting diodes (LEDs) (EVIS X1: CV-1500, Olympus Co., Tokyo, Japan) was released worldwide in July 2020. In addition to the improvement of narrow band imaging (NBI), this system enables texture and color enhancement imaging (TXI). TXI makes the lesion reddish and supports better visibility of colorectal lesions in comparison to white light imaging for improving lesion detection. On the other hand, another 4-color LED endoscope system (ELUXEO: BL-7000; Fujifilm, Tokyo, Japan) has been on the market in the West since 2017. This system enables blue light imaging (BLI) and linked color imaging (LCI). Generally, the accurate comparison between two images obtained by two different endoscope systems is difficult. To resolve this problem, we developed a method named the tablet-image comparison (TIC) method. TIC is a simple, easy, and paperless method to get images under similar conditions of two endoscope systems for an accurate comparison. We herein report two colorectal lesions in which accurate comparisons of images between TXI and LCI and between improved NBI and BLI obtained in the EVIS X1 and ELUXEO systems were performed using the TIC method. One was IIa 30 mm (high-grade dysplasia) and the other was IIa 25 mm (low-grade adenoma). A detailed comparison between TXI and LCI could be performed by TIC. In these two cases, with a distant view, TXI showed greater redness than LCI. LCI showed slightly higher brightness than TXI. In magnified TXI and LCI, the irregularities observed were similar to NBI and BLI, respectively.

The Efficacy of Tumor Characterization for Colorectal Lesions with Blue Light Imaging of a Compact Light-Emitting Diode Endoscopic System Compared to a Laser Endoscopic System: A Pilot Study.

Background: A compact and cost-effective light source-processor combined 3-color light-emitting diode (LED) endoscopic system (ELUXEO-Lite: EP-6000, Fujifilm Co., Tokyo) with a magnified colonoscope (EC-6600ZP, Fujifilm Co.) has been released. Aims: In this study, we analyzed the efficacy of this system for colorectal tumor characterization with magnified blue light imaging (BLI-LED) and image's subjective and objective evaluations, compared to a magnified blue laser imaging (BLI-LASER) using a standard LASER endoscopic system. Methods: We retrospectively reviewed 37 lesions observed with both BLI-LED and BLI-LASER systems from 2019 using the Japanese narrow band imaging classification. Two representative magnified images, one BLI-LED and one BLI-LASER, of the same area of a lesion were evaluated for diagnostic accuracy and visualization quality by three experts and three non-experts. Their color difference values (CDVs) and brightness values (BVs) were also calculated as objective indicators. Results: Among 37 lesions, mean tumor size was 18.9 ± 13.1 mm, and 21 lesions were nonpolypoid. Histopathology revealed 14 sessile serrated lesions, 7 adenomas, 12 high-grade dysplasias and T1a cancers, and 4 T1b cancers. The diagnostic accuracy rates of BLI-LED/BLI-LASER of experts and non-experts were 90.1% and 87.4% (p = 0.52) and 89.2% and 89.2% (p = 0.99). The percentages of instances where BLI-LED images were better, the two imaging types were equivalent, or BLI-LASER images were better were 16%/83%/1% for experts and 19%/58%/23% for non-experts (p < 0.001). CDVs and BVs between BLI-LED and BLI-LASER were not significantly different (CDVs: p = 0.653, BVs: p = 0.518). Conclusions: BLI-LED using the compact system was noninferior to BLI-LASER for colorectal tumor characterization and image quality.

The usefulness of combining the pocket-creation method with a traction device using a scissor-type knife for colorectal endoscopic submucosal dissection.

INTRODUCTION: Technical issues and long procedure time still remain a concern in colorectal endoscopic submucosal dissection (ESD). We examined the usefulness of combining the pocket-creation method (PCM) with a traction device (S-O clip; SO) using a scissor-type knife (Clutch Cutter 3.5 mm; CC) for decreasing ESD procedure time. METHODS: We retrospectively analyzed 95 ESD cases of PCM + SO + CC managed from August 2017 to April 2020 and 103 cases of PCM + CC treated from July 2016 to July 2017. We compared these two groups through propensity score matching. The main outcome was the analysis of the ESD procedure times under various conditions in each group. RESULTS: After matching, 52 cases in the PCM + SO + CC and PCM + CC groups were analyzed. The PCM + SO + CC group showed a significantly shorter ESD procedure time than the PCM + CC group (57.8 ± 31.4 vs. 81.7 ± 33.5 min, p < 0.01). Additionally, the ESD procedure time was significantly shorter in the PCM + SO + CC group than in the PCM + CC group: tumor size (tumor size < 40 mm: 45.6 ± 15.8 vs. 72.7 ± 22.9 min, p < 0.01; tumor size ≥ 40 mm: 83.1 ± 40.1 vs. 111.8 ± 45.3 min, p = 0.04), tumor location (right side: 64.7 ± 33.3 vs. 81.0 ± 29.7 min, p = 0.03; left side: 50.5 ± 28.0 vs. 82.3 ± 36.9 min, p < 0.01), tumor morphology (polypoid: 39.2 ± 18.6 vs. 74.7 ± 28.6 min, p < 0.01; nonpolypoid: 62.3 ± 32.3 vs. 84.5 ± 35.2 min, p < 0.01), endoscopist (expert: 67.3 ± 41.2 vs. 91.9 ± 40.2 min, p = 0.02; nonexpert: 50.4 ± 18.3 vs. 73.6 ± 24.9 min, p < 0.01), and fibrosis (severe fibrosis: 82.0 ± 20.5 vs. 99.8 ± 40.4 min, p = 0.169; non-severe fibrosis: 52.1 ± 23.8 vs. 75.6 ± 29.0 min, p < 0.01). CONCLUSIONS: The combination of the PCM and SO using CC achieved a reduction in the colorectal ESD procedure time.

A Case of Fifteen Simultaneous Rectal Neuroendocrine Tumors and Endocrine Cell Micronests Resected by Both Endoscopic Treatments and Surgery.

Case Report: A 65-year-old man without any symptoms received colonoscopy for cancer screening and underwent cold snare polypectomy (CSP) for a 3-mm rectal lesion at a local clinic. A histopathological examination revealed neuroendocrine tumor (NET) G1 with a positive margin. The patient was referred to our hospital for further treatment. Then, the post-CSP scar was removed by endoscopic submucosal dissection (ESD), with a sufficient endoscopically normal margin. Histopathology showed 4 NETs and endocrine cell micronests (ECMs) distant from the post-CSP scar, with a positive lateral margin. We considered that the possibility of other NETs was high. Additional surgery was performed. After a histopathological examination, 11 NETs and ECMs were found in the whole rectum, without lymph node metastasis. The patient had no recurrence at 24 months after surgery. In the past 10 years, we have experienced 4 cases (including the present case) of multiple rectal NETs among 56 cases of rectal NETs of ≤10 mm (7.1%). None of our 4 cases showed any recurrence (follow-up period: 12-32 months). Conclusions: We herein report a case involving a patient with 15 rectal NETs and ECMs. We reviewed our experience with multiple rectal NETs, and the rate of multiple rectal NETs was 7.1%. Endoscopists should consider that multiple lesions may be present in cases of rectal NET and be aware that some cannot be detected endoscopically.

Association Between the Cool Temperature-dependent Suppression of Colonic Peristalsis and Transient Receptor Potential Melastatin 8 Activation in Both a Randomized Clinical Trial and an Animal Model.

Background/Aims: Several studies have assessed the effect of cool temperature on colonic peristalsis. Transient receptor potential melastatin 8 (TRPM8) is a temperature-sensitive ion channel activated by mild cooling expressed in the colon. We examined the antispasmodic effect of cool temperature on colonic peristalsis in a prospective, randomized, single-blind trial and based on the video imaging and intraluminal pressure of the proximal colon in rats and TRPM8-deficient mice. Methods: In the clinical trial, we randomly assigned a total of 94 patients scheduled to undergo colonoscopy to 2 groups: the mildly cool water (n = 47) and control (n = 47) groups. We used 20 mL of 15°C water for the mildly cool water. The primary outcome was the proportion of subjects with improved peristalsis after treatment. In the rodent proximal colon, we evaluated the intraluminal pressure and performed video imaging of the rodent proximal colon with cool water administration into the colonic lumen. Clinical trial registry website (Trial No. UMIN-CTR; UMIN000030725). Results: In the randomized controlled trial, after treatment, the proportion of subjects with no peristalsis with cool water was significantly higher than that in the placebo group (44.7% vs 23.4%; P < 0.05). In the rodent colon model, cool temperature water was associated with a significant decrease in colonic peristalsis through its suppression of the ratio of peak frequency (P < 0.05). Cool temperature-treated TRPM8-deficient mice did not show a reduction in colonic peristalsis compared with wild-type mice. Conclusion: For the first time, this study demonstrates that cool temperature-dependent suppression of colonic peristalsis may be associated with TRPM8 activation.

Effects of the combined use of a scissor-type knife and traction clip on endoscopic submucosal dissection of colorectal tumors: a propensity score-matched analysis.

Background and study aims This study evaluated the technical aspects of colorectal endoscopic submucosal dissection (ESD) with the Clutch Cutter (CC) (Fujifilm Co., Tokyo, Japan), a scissor-type knife, and the S-O clip (SO) as a traction clip, and compared the safety and efficacy to ESD using a needle-type knife. Patients and methods This was a single-center retrospective study. In Study 1, we evaluated 125 ESD patients: 60 using the SO and CC (SO group) and 65 using the CC (CC group). In Study 2, we evaluated 185 ESD patients: the CC group (N = 65) and 120 using the Flush knife BT-S (Flush group) (Fujifilm Co., Tokyo, Japan). In both studies, the clinicopathological features and therapeutic outcomes were compared using a propensity score-matched analysis. Results In 36 pairs of matched patients in Study 1, the rates of en bloc resection, R0 resection, perforation, and postoperative bleeding (POB) were 97.2 %, 88.9 %, 2.8 %, and 0 %, respectively, for the SO group and 100 %, 91.7 %, 0 %, and 0 % for the CC group (not significant). The mean procedure time for the SO group among less-experienced endoscopists was significantly shorter than in the CC group (42 vs. 65 minutes, P  = 0.036). In 49 pairs of matched patients in Study 2, the rates of en bloc resection, R0 resection, perforation, and POB were 100 %, 95.8 %, 0 %, and 0 %, respectively, for the CC group and 98.0 %, 95.8 %, 0 %, and 2.0 % for the Flush group (not significant). The mean procedure time in the CC group among less-experienced endoscopists was significantly shorter than in the Flush group (52 vs. 67 minutes, P  = 0.038). Conclusions CC and the combined use of CC and SO reduced colorectal ESD procedure time among less-experienced endoscopists.

Differences between two sodium hyaluronate-based submucosal injection materials currently used in Japan based on viscosity analysis.

In Japan, two 0.4% sodium hyaluronate (HA)-based submucosal injection materials (SIMs) are currently used in endoscopic submucosal dissection (ESD): MucoUp (HA-Mc) and Ksmart (HA-Ks). HA-Mc and HA-Ks have the same concentration and are, thus, construed by most endoscopists to have no difference. Nevertheless, visual observation conveys the impression that HA-Ks have a higher viscosity than HA-Mc, suggesting that HA-Ks performs better than HA-Mc. This study aimed to examine the differences between HA-Mc and HA-Ks. HA-Ks exhibited higher viscosity due to greater weight-average molecular weight compared with HA-Mc. HA-Ks had significantly greater submucosal elevation height (SEH) than HA-Mc; the SEH of HA-Ks-80% (80% dilution of HA-Ks) was the same as that of HA-Mc. The ESD procedure time was significantly shorter with HA-Ks than with HA-Mc (15.2 ± 4.1 vs. 19.5 ± 5.9; P = 0.049). The total injection volume for HA-Ks was significantly lower than that for HA-Mc (10.8 ± 3.6 vs. 14.4 ± 4.6; P = 0.045). However, no significant difference in these items was observed between HA-Mc and HA-Ks-80%. HA-Mc and HA-Ks were considered to be almost the same. Nonetheless, HA-Ks exhibited higher viscosity and SIM performance than HA-Mc. HA-Ks-80% had almost the same performance as HA-Mc. Thus, understanding SIM performance and characteristics requires a focus on the viscosity of SIMs.