Vertical margin distance in T1 colorectal carcinoma resected by endoscopic submucosal dissection affects prognosis after additional surgery.

PURPOSE : A vertical margin (VM) distance of < 500 µm is a risk factor for recurrence in patients with T1 colorectal carcinoma (CRC) resected by endoscopy. We aimed to determine the effects of the VM distance on the recurrence and prognosis of T1 CRC. METHODS: We enrolled 168 patients with T1 CRC who underwent additional surgery after endoscopic submucosal dissection (ESD) at multiple centers between 2008 and 2016. None of the patients were followed up for < 5 years. The enrolled 168 patients were classified into patients with VM distance of < 500 µm including positive VM (n = 72 [43%], VM distance < 500 µm group) and patients with VM distance of ≥ 500 µm (n = 96 [57%], VM distance ≥ 500 µm group). The clinicopathological features, recurrence rates, and prognoses were compared between the groups using propensity-score matching (PSM). RESULTS: Tumors recurred in eight of the 168 patients (5%) with VM distance < 500 µm. After PSM, the rate of overall recurrence and local recurrence in the VM distance < 500 µm group were significantly higher than those in the VM distance ≥ 500 µm group. The 5-year recurrence-free survival rate was significantly higher in the VM distance ≥ 500 µm group than that in VM distance < 500 µm group after PSM (100% vs. 89%, p < 0.012). CONCLUSIONS: Complete en bloc resection of T1 CRC via ESD must include a sufficient amount of SM to reduce the risk of metastasis and recurrence after additional surgery.

Usefulness and Educational Benefit of a Virtual Scale Endoscope in Measuring Colorectal Polyp Size.

INTRODUCTION: The virtual scale endoscope (VSE) is a newly introduced endoscope that helps endoscopists in measuring colorectal polyp size (CPS) during colonoscopy by displaying a virtual scale. This study aimed to determine the usefulness of the VSE for CPS measurement and the educational benefit of using VSE images to improve CPS estimation accuracy. METHODS: This study included 42 colorectal polyps in 26 patients treated at Hiroshima University Hospital. In study 1, CPS measured using a VSE before endoscopic mucosal resection was compared with CPS measured on resected specimens, and the agreement between the two measurement methods was evaluated via Bland-Altman analysis. In study 2, 14 endoscopists (5 beginners, 5 intermediates, and 4 experts) took a pre-test to determine the size of 42 polyps. After the pre-test, a lecture on CPS measurement using VSE images was given. One month later, the endoscopists took a post-test to compare CPS accuracy before and after the lecture. RESULTS: In study 1, Bland-Altman analysis revealed no fixed or proportional errors. The mean bias ±95% limits of agreement (±1.96 standard deviations) of the measurement error was -0.05 ± 0.21 mm, indicating that the agreement between two measurement methods was sufficient. In study 2, the accuracy of CPS measurement was significantly higher among beginners (59.5% vs. 26.7%, p < 0.01) and intermediates (65.2% vs. 44.3%, p < 0.05) in the post-test than in the pre-test. CONCLUSION: The VSE accurately measures CPS before resection, and its images are useful teaching tools for beginner and intermediate endoscopists.

Characteristics and Prognosis of Sporadic Neoplasias Detected in Patients with Ulcerative Colitis.

INTRODUCTION: Patients with ulcerative colitis (UC) develop not only UC-associated neoplasias but also sporadic neoplasias (SNs). However, few studies have described the characteristics of SNs in patients with UC. Therefore, this study aimed to evaluate the clinical features and prognosis of SNs in patients with UC. METHODS: A total of 141 SNs in 59 patients with UC, detected by surveillance colonoscopy at Hiroshima University Hospital between January 1999 and December 2021, were included. SNs were diagnosed based on their location, endoscopic features, and histopathologic findings along with immunohistochemical staining for Ki67 and p53. RESULTS: Of the SNs, 91.5% were diagnosed as adenoma and 8.5% were diagnosed as carcinoma (Tis carcinoma, 3.5%; T1 carcinoma, 5.0%). 61.0% of the SNs were located in the right colon, 31.2% were located in the left colon, and 7.8% were located in the rectum. When classified based on the site of the lesion, 70.9% of SNs occurred outside and 29.1% within the affected area. Of all SNs included, 95.7% were endoscopically resected and 4.3% were surgically resected. Among the 59 patients included, synchronous SNs occurred in 23.7% and metachronous multiple SNs occurred in 40.7% during surveillance. The 5-year cumulative incidence of metachronous multiple SNs was higher in patients with synchronous multiple SNs (54.2%) than in those without synchronous multiple SNs (46.4%). CONCLUSION: Patients with UC with synchronous multiple SNs are at a higher risk of developing metachronous multiple SNs and may require a closer follow-up by total colonoscopy than patients without synchronous SNs.

Hybrid endoscopic submucosal dissection as a salvage option for difficult colorectal conventional endoscopic submucosal dissection.

BACKGROUND: When total submucosal dissection is difficult to achieve during conventional colorectal endoscopic submucosal dissection (C-ESD), the lesion can be resected by final snaring through salvage hybrid ESD (SH-ESD). This study aimed to examine the outcomes of SH-ESD and identify its indications that could achieve en bloc resection. METHODS: We recruited 1039 consecutive patients with colorectal lesions that underwent ESD at Hiroshima University Hospital between January 2015 and December 2020. C-ESD was attempted thoroughly in 924 lesions (C-ESD group, including 9 lesions in which ESD was discontinued), and SH-ESD was performed owing to some difficulties in 115 lesions (SH-ESD group). Risk factors for incomplete resection by SH-ESD and ESD discontinuation were evaluated using multivariate analysis. The outcomes were compared between cases with remaining undissected submucosa of < 20 mm in diameter in the SH-ESD and C-ESD groups, using propensity score matching. RESULTS: Multivariate analysis revealed that a procedure time > 80 min and remaining undissected submucosa ≥ 20 mm in diameter were significant risk factors for incomplete resection after SH-ESD and ESD discontinuation. By propensity score matching analysis, procedure time was significantly shorter in the SH-ESD group with remaining undissected submucosa < 20 mm in diameter than in the C-ESD group (71 min vs. 90 min, p = 0.0053), although no significant difference was found in the en bloc resection rate (94% vs. 87%, p = 0.0914). CONCLUSION: SH-ESD can be an alternative surgical method when conventional ESD is difficult to continue in cases in which the remaining undissected submucosa is < 20 mm in diameter.

Efficacy and safety comparison of scissor-type knives with needle-type knives for colorectal endoscopic submucosal dissection: a post-hoc propensity score-matched analysis (with videos).

BACKGROUND AND AIMS: Many knives have been developed to improve the efficacy and safety of endoscopic submucosal dissection (ESD). We aimed to evaluate the efficacy and safety of scissor-type knives for colorectal ESD compared with needle-type knives. METHODS: We performed a post-hoc propensity score-matched analysis in an 11-facility study between August 2013 and December 2018. A total of 2330 patients (2498 lesions) who underwent colorectal ESD were divided into needle-type (1923 patients, 2067 lesions) and scissor-type (407 patients, 431 lesions) knife groups. Short-term outcomes were compared between the 2 groups. RESULTS: Two-to-one propensity score-matched analysis identified 814 (709 patients) and 407 (386 patients) lesions in the needle- and scissor-type knife groups, respectively. The median resection speed was significantly faster in the needle-type group (18.3 mm2/min) than in the scissor-type group (13.2 mm2/min, P < .0001), whereas en-bloc and histologic complete resection rates were not significantly different between the needle- and scissor-type groups (96.8% [788/814] vs 98.3% [400/407], P = .1888 and 95.1% [774/814] vs 95.6% [389/407], P = .7763, respectively). The rate of lesions resected using a single knife was significantly higher in the scissor-type group (98.5% [401/407]) than in the needle-type group (43.9% [357/814], P < .0001). Rates of intraoperative perforation and delayed bleeding were significantly lower in the scissor-type group than in the needle-type group (.7% [3/407] vs 2.5% [20/814], P = .0431 for each). CONCLUSIONS: Scissor-type knives are safer for colorectal ESD. However, they are associated with slower resection speeds compared with needle-type knives. (Clinical trial registration number: UMIN000016197.).

Novel endoscopic ultrasonography classification for assured vertical resection margin (≥500 µm) in colorectal endoscopic submucosal dissection.

BACKGROUND AND AIM: The risk of local recurrence might be low in pT1 colorectal carcinoma with a tumor vertical margin (VM) ≥500 µm. We investigated the relationship between endoscopic ultrasonography (EUS) findings and VM in cases with colorectal endoscopic submucosal dissection (ESD) categorized as Type 2B according to the Japan NBI Expert Team (JNET) classification. METHODS: We analyzed 179 JNET Type 2B colorectal tumors resected by ESD at Hiroshima University Hospital from January 2010 to May 2021. The distance from the tumor invasive front to the muscle layer on EUS was defined as the tumor-free distance (EUS-TFD) and classified as Type I (EUS-TFD ≥1 mm) and II (<1 mm). We investigated the relationship between EUS-TFD and VM and analyzed the predictive factors for VM ≥500 µm. RESULTS: EUS-TFD Type I was diagnosed in 133 (74.3%) lesions: VM ≥500 µm (114, 85.7%); VM <500 µm (19, 14.3%); and VM positive (VM1) (0, 0%). Type II was diagnosed in 46 (25.7%) lesions: VM ≥500 µm (14, 30.5%); VM <500 µm (22, 47.8%); and VM1 (10, 21.7%). In the EUS-TFD Type I cases, 84.5% and 87.8% were protruded and superficial types; whereas for Type II cases, these were 38.9% and 25%, respectively. EUS-TFD classification (Type I), scope operability (good), submucosal invasion depth (<2000 µm), histology at the deepest invasive portion (favorable), and degree of fibrosis (F0/F1) were significant predictors of VM ≥500 µm. CONCLUSIONS: In JNET Type 2B lesions, EUS-TFD classification is a novel diagnostic indicator to predict VM ≥500 µm in ESD preoperatively.

Development of multi-class computer-aided diagnostic systems using the NICE/JNET classifications for colorectal lesions.

BACKGROUND AND AIM: Diagnostic support using artificial intelligence may contribute to the equalization of endoscopic diagnosis of colorectal lesions. We developed computer-aided diagnosis (CADx) support system for diagnosing colorectal lesions using the NBI International Colorectal Endoscopic (NICE) classification and the Japan NBI Expert Team (JNET) classification. METHODS: Using Residual Network as the classifier and NBI images as training images, we developed a CADx based on the NICE classification (CADx-N) and a CADx based on the JNET classification (CADx-J). For validation, 480 non-magnifying and magnifying NBI images were used for the CADx-N and 320 magnifying NBI images were used for the CADx-J. The diagnostic performance of the CADx-N was evaluated using the magnification rate. RESULTS: The accuracy of the CADx-N for Types 1, 2, and 3 was 97.5%, 91.2%, and 93.8%, respectively. The diagnostic performance for each magnification level was good (no statistically significant difference). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the CADx-J were 100%, 96.3%, 82.8%, 100%, and 96.9% for Type 1; 80.3%, 93.7%, 94.1%, 79.2%, and 86.3% for Type 2A; 80.4%, 84.7%, 46.8%, 96.3%, and 84.1% for Type 2B; and 62.5%, 99.6%, 96.8%, 93.8%, and 94.1% for Type 3, respectively. CONCLUSIONS: The multi-class CADx systems had good diagnostic performance with both the NICE and JNET classifications and may aid in educating non-expert endoscopists and assist in diagnosing colorectal lesions.

Vertical tumor margin of endoscopic resection for T1 colorectal carcinoma affects the prognosis of patients undergoing additional surgery.

BACKGROUND: Vertical tumor margin-negative T1 colorectal carcinoma (CRC) is an absolute curative condition following complete endoscopic resection (ER). However, the influence on prognosis in relation to vertical tumor margin is unclear. Therefore, we evaluated the influence of the distance from vertical tumor margin to resected specimen edge (vertical margin distance) of ER for T1b (submucosal invasion depth > 1000 µm) CRC on the prognosis of patients undergoing additional surgery after ER. METHODS: In total, 215 consecutive patients with T1b CRC who underwent additional surgery after ER at Hiroshima University Hospital between February 1992 and June 2019 were enrolled. We assessed 191 patients without lymph node metastases at the additional surgery. The specimens resected by ER were classified into three groups based on the vertical margin distance: patients with a vertical margin distance of ≥ 500 µm (Group A); patients with a vertical margin distance of < 500 µm (Group B); and patients with a positive vertical tumor margin (Group C). Subsequently, we evaluated the prognosis of the patients in relation to the clinicopathological characteristics among the three groups. RESULTS: There were no significant differences in clinicopathological characteristics among the three groups. Group A had a significantly higher recurrence-free 5-year survival rate than Groups B and C (100%, 84.5%, and 81.8%, respectively). Similarly, Group A had a significantly higher disease-specific 5-year survival rate than Group C (100% vs. 95.5%). CONCLUSIONS: Complete en bloc resection with sufficient submucosal layer from the invasive front (vertical margin distance > 500 µm) by ER for T1 CRC reduces the risk of metastatic recurrence after additional surgery.

Factors for conversion risk of colorectal endoscopic submucosal dissection: a multicenter study.

BACKGROUND: Endoscopic submucosal dissection (ESD) has become a widely accepted treatment method for colorectal tumors; however, there are some persistent problems. This multi-center study aimed to characterize the risk factors for incomplete resection and perforation in standardized colorectal ESD procedures. METHODS: This study included 2423 consecutive patients who underwent ESD for 2592 colorectal tumors between August 2013 and December 2018 at 11 institutions (1 academic hospital and 10 affiliated hospitals) from the Hiroshima GI Endoscopy Research Group. We evaluated the risk factors for interruption, piecemeal resection, and perforation of standardized colorectal ESD in relation to clinicopathologic and endoscopic characteristics. RESULTS: The incidences of interruption, piecemeal resection, and perforation were 0.7%, 2.9%, and 3.0%, respectively. Multivariate analysis identified the following risk factors for interruption: perforation during the procedure, deep submucosal invasion (> 1000 µm), poor scope operability, and severe submucosal fibrosis. The risk factors for piecemeal resection included poor scope operability, severe submucosal fibrosis, and procedure time (≥ 85 min). The risk factors for perforation during the procedure were severe submucosal fibrosis, poor scope operability, procedure time (≥ 85 min), and tumor size (≥ 40 mm). Independent risk factors for severe submucosal fibrosis included a history of biopsy and lesions located on the fold or flexure. CONCLUSIONS: Severe submucosal fibrosis and poor scope operability are the common risk factors for interruption, piecemeal resection, and perforation in standardized colorectal ESD.

Long-term prognosis after endoscopic submucosal dissection for colorectal tumors in patients aged over 80 years.

BACKGROUND: In Japan, endoscopic submucosal dissection (ESD) is standardized for large colorectal tumors. However, its validity in the elderly population is unclear. We aimed to evaluate the safety and efficacy of ESD for colorectal tumors in elderly patients aged over 80 years. METHODS: ESD was performed on 178 tumors in 165 consecutive patients aged over 80 years between December 2008 and December 2018. We retrospectively evaluated the clinicopathological characteristics and clinical outcomes of ESD. We also assessed the prognosis of 160 patients followed up for more than 12 months. RESULTS: The mean patient age was 83.7 ± 3.1 years. The number of patients with comorbidities was 100 (62.5%). Among all patients, 106 (64.2%) were categorized as class 1 or 2 according to the American Society of Anesthesiologists classification of physical status (ASA-PS), and 59 (35.8%) were classified as class 3. The mean procedure time was 97.7 ± 79.3 min. The rate of histological en bloc resection was 93.8% (167/178). Delayed bleeding in 11 cases (6.2%) and perforation in 7 cases (3.9%) were treated conservatively. The 5-year survival rate was 89.9%. No deaths from primary disease (mean follow-up time: 35.3 ± 27.5 months) were observed. Overall survival rates were significantly lower in the non-curative resection group that did not undergo additional surgery than in the curative resection group (P = 0.0152) and non-curative group that underwent additional surgery (P = 0.0259). Overall survival rates were higher for ASA-PS class 1 or 2 patients than class 3 patients (P = 0.0105). Metachronous tumors (> 5 mm) developed in 9.4% of patients. CONCLUSIONS: ESD for colorectal tumors in patients aged over 80 years is safe. Colorectal cancer-associated deaths were prevented although comorbidities pose a high risk of poor prognosis.

Effect of educational lecture on the diagnostic accuracy of Japan NBI Expert Team classification for colorectal lesions.

BACKGROUND: An educational and training program is required for generalization of Japan NBI Expert Team (JNET) classification. However, there is no detailed report on the learning curve of the diagnostic accuracy of endoscopists using JNET classification. We examined the effect of an educational lecture on beginners and less experienced endoscopists for improving their diagnostic accuracy of colorectal lesions by JNET classification. METHODS: Seven beginners with no endoscopy experience (NEE group), 7 less experienced endoscopists (LEE group), and 3 highly experienced endoscopists (HEE group) performed diagnosis using JNET classification for randomized NBI images of colorectal lesions from 180 cases (Type 1: 22 cases, Type 2A: 105 cases, Type 2B: 33 cases, and Type 3: 20 cases). Next, the NEE and LEE groups received a lecture on JNET classification, and all 3 groups repeated the diagnostic process. We compared the correct diagnosis rate and interobserver agreement before and after the lecture comprehensively and for each JNET type. RESULTS: In the HEE group, the correct diagnosis rate was more than 90% with good interobserver agreements (kappa value: 0.78-0.85). In the NEE and LEE groups, the correct diagnosis rate (NEE: 60.2 → 68.0%, P < 0.01; LEE: 66.4 → 86.7%, P < 0.01), high-confidence correct diagnosis rate (NEE: 19.6 → 37.2%, P < 0.01; LEE: 43.6 → 61.1%, P < 0.01), and interobserver agreement (kappa value, NEE: 0.32 → 0.43; LEE: 0.39 → 0.75) improved after the lecture. In the examination by each JNET type, the specificity and positive predictive value in the NEE and LEE groups generally improved after the lecture. CONCLUSION: After conducting an appropriate lecture, the diagnostic ability using JNET classification was improved in beginners or endoscopists with less experience in NBI magnifying endoscopy.

Clinical outcomes of endoscopic resection for rectal neuroendocrine tumors: Advantages of endoscopic submucosal resection with a ligation device compared to conventional EMR and ESD.

Objectives: There are some endoscopic resection (ER) methods for neuroendocrine tumors (NETs), however, which method is most useful remains unclear. This study aimed to compare the outcomes of different ER techniques, such as conventional endoscopic mucosal resection (cEMR), endoscopic submucosal dissection (ESD), and endoscopic submucosal resection with a ligation device (ESMR-L) for rectal NETs. Methods: We retrospectively analyzed 96 consecutive patients with 102 rectal NETs of less than 10 mm in diameter who underwent ER between January 2001 and December 2019 at Hiroshima University Hospital. We compared the clinical outcomes of each ER method (cEMR 60 lesions, ESD 21 lesions, and ESMR-L 21 lesions), divided according to the treatment periods, and evaluated the risk factors for vertical margin (VM) positivity in relation to clinicopathological and endoscopic characteristics. Results: As for the mean procedure time, ESD took significantly longer to perform than the other methods. The histological complete resection rate was 80% (48/60) for cEMR, 85.7% (18/21) for ESD, and 100% (21/21) for ESMR-L, and the VM positive rate was 20% (12/60) for cEMR, 14.3% (3/21) for ESD, and 0% (0/21) for ESMR-L, with no significant difference. However, the tumor-front-to-VM distance was significantly longer in the ESMR-L group than in the cEMR and ESD groups. cEMR and ESD were both significant risk factors for VM positivity. No perforation or local recurrence was observed in all methods. Conclusions: ESMR-L is the most useful ER method for small rectal NETs.

Efficacy of single-balloon overtube for endoscopic submucosal dissection in the proximal colon: A propensity score-matched analysis.

Objectives: A single-balloon overtube (SBO) can improve poor scope operability during colonic endoscopic submucosal dissection (ESD). We aimed to evaluate the clinical usefulness of SBO for ESD in the proximal colon and the predictive factors for cases in which SBO is useful. Methods: A total of 88 tumors located in the proximal colon resected by balloon-assisted ESD (BA-ESD) using SBO and 461 tumors resected by conventional ESD (C-ESD) between June 2015 and November 2020 were considered. Seventy-eight tumors each in the BA-ESD and C-ESD groups were matched by propensity score matching. ESD outcomes were compared between the groups, and a decision tree analysis was performed to explore the predictive factors for cases in which SBO is useful. Results: There were no significant differences between the groups in the major outcomes such as en bloc resection rate (95% vs. 99%, p = 0.17), R0 resection rate (92% vs. 96%, p = 0.30), mean dissection speed (16 mm2/min vs. 16 mm2/min, p = 0.53), and intraoperative perforation rate (5% vs. 6%, p = 0.73). Even when considering cases with poor preoperative scope operability, there were no significant differences between the groups. Comparison of tumors ≥40 mm in diameter between the groups confirmed that the intraoperative perforation rate was significantly lower in the BA-ESD group than in the C-ESD group (0% vs. 24%, p = 0.0188). Conclusion: SBO is useful for ESD of tumors ≥40 mm in diameter in the proximal colon to prevent intraoperative perforation, which usually has a long procedure time.

Risk of Bleeding after Colorectal Endoscopic Resection in Patients with Continued Warfarin Use Compared to Heparin Replacement: A Propensity Score Matching Analysis.

The Japan Gastroenterological Endoscopy Society (JGES) guidelines recommend continued warfarin treatment during gastroenterological endoscopic procedures with a high risk of bleeding as an alternative to heparin replacement in patients on warfarin therapy. However, there is insufficient evidence to support the use of warfarin in colorectal endoscopic resection (ER). The present study is aimed at verifying the risk of bleeding after ER for colorectal neoplasia (CRN) in patients with continued warfarin use. This was a single-center retrospective cohort study using clinical records. We assessed 126 consecutive patients with 159 CRNs who underwent ER (endoscopic mucosal resection, 146 cases; endoscopic submucosal dissection, 13 cases) at Hiroshima University Hospital between January 2014 and December 2019. Patients were divided into two groups: the heparin replacement group (79 patients with 79 CRNs) and the continued warfarin group (47 patients with 80 CRNs). One-to-one propensity score matching was performed to compare the bleeding rate after ER between the groups. The rate of bleeding after ER was significantly higher in the heparin replacement group than in the continued warfarin group for both before (10.1% vs. 1.3%, respectively; P = 0.0178) and after (11.9% vs. 0%, respectively; P = 0.0211) propensity score matching. None of the patients experienced thromboembolic events during the perioperative period. The risk of bleeding after colorectal ER was significantly lower in patients with continued warfarin use than in those with heparin replacement. Our data supports the recommendations of the latest JGES guidelines for patients receiving warfarin therapy.

Clinical usefulness of hybrid endoscopic submucosal dissection for T1b colorectal carcinomas ≤20 mm to ensure adequate vertical margins.

Objective: To evaluate endoscopic resection strategies for cT1b colorectal carcinomas (CRCs) ≤20 mm to determine strategies that enable adequate vertical margins (VMs). Methods: We enrolled 128 consecutive patients with cT1b colorectal carcinomas ≤20 mm resected by endoscopic mucosal resection or hybrid endoscopic submucosal dissection (ESD). Tumor lifting conditions after submucosal injection were classified into type A (lifting, soft dome-like), type B (lifting, hard trapezoid-like), and non-lifting (positive non-lifting sign). Predictors of positive VMs (VM 1) and adequate VMs were identified. Results: All non-lifting tumors were resected by hybrid ESD and VMs were ≥500 µm. Vertical margin 1 tumors were only found in the endoscopic mucosal resection group, in which, the proportion of type B tumors with VM 1 was significantly higher than that of tumors with negative VMs (p < 0.01). Type A tumors showed no significant between-group differences. Among type B tumors, the proportion of VMs ≥500 µm was significantly higher (p < 0.01) and the VM distance was significantly longer (p < 0.01) in the hybrid ESD group than in the endoscopic mucosal resection group. Conclusions: Hybrid ESD can be selected for type B tumors to ensure adequate VMs.