Exploratory investigation of virtual lesions in gastrointestinal endoscopy using a novel phase-shift method for three-dimensional shape measurement.

Accurate measurement of the size of lesions or distances between any two points during endoscopic examination of the gastrointestinal tract is difficult owing to the fisheye lens used in endoscopy. To overcome this issue, we developed a phase-shift method to measure three-dimensional (3D) data on a curved surface, which we present herein. Our system allows the creation of 3D shapes on a curved surface by the phase-shift method using a stripe pattern projected from a small projecting device to an object. For evaluation, 88 measurement points were inserted in porcine stomach tissue, attached to a half-pipe jig, with an inner radius of 21 mm. The accuracy and precision of the measurement data for our shape measurement system were compared with the data obtained using an Olympus STM6 measurement microscope. The accuracy of the path length of a simulated protruded lesion was evaluated using a plaster model of the curved stomach and graph paper. The difference in height measures between the measurement microscope and measurement system data was 0.24 mm for the 88 measurement points on the curved surface of the porcine stomach. The error in the path length measurement for a lesion on an underlying curved surface was <1% for a 10-mm lesion. The software was developed for the automated calculation of the major and minor diameters of each lesion. The accuracy of our measurement system could improve the accuracy of determining the size of lesions, whether protruded or depressed, regardless of the curvature of the underlying surface.

Long-term outcomes after non-curative endoscopic resection for esophageal squamous cell carcinoma followed by additional chemoradiotherapy.

Endoscopic resection (ER) of esophageal squamous cell carcinoma (ESCC) is evaluated pathologically, and additional treatment is recommended for cases resulting in non-curative resection, defined as pMM with lymphovascular invasion (LVI), pSM, or positive vertical margin. This study aimed to assess long-term outcomes and risk factors for recurrence in patients with ESCC treated with non-curative ER followed by additional chemoradiotherapy (CRT). We retrospectively reviewed the clinical courses of patients who underwent non-curative ER followed by additional CRT for ESCCs between August 2007 and December 2017. Recurrence rates and risk factors for recurrence were analyzed. Among 97 patients with non-curative ER, 73 underwent additional CRT. With a median follow-up period of 71 months, recurrences were observed in 10 (14%) of 73 patients, with a median interval of 24.5 (1-59 months). The 3- and 5-year recurrence-free survival were 89 and 85%, respectively, and the 3- and 5-year overall survival rates were 96 and 91%, respectively. Multivariate analysis showed that lymphatic invasion was an independent risk factor for recurrence in patients with non-curative ESCC receiving additional CRT. Among the 10 patients with recurrence, 4, 3, 2, and 1 underwent surgery, chemotherapy, supportive care, and CRT, respectively. Notably, all four patients who underwent surgery survived, regardless of regional and/or distant lymph node metastasis. Lymphatic invasion is an independent risk factor for the recurrence of non-curative ESCCs. Careful follow-up is required for at least 5 years after ER with additional CRT.

Evaluating the usefulness of considering the size and morphological type of type B2 vessel area based on Japan Esophageal Society classification in estimating tumor invasion depth in superficial esophageal squamous cell carcinomas: study protocol for a prospective observational study (Japan BEES study).

BACKGROUND: Accurate evaluation of tumor invasion depth is essential to determine the appropriate treatment strategy for patients with superficial esophageal cancer. The pretreatment tumor depth diagnosis currently relies on the magnifying endoscopic classification established by the Japan Esophageal Society (JES). However, the diagnostic accuracy of tumors involving the muscularis mucosa (MM) or those invading the upper third of the submucosal layer (SM1), which correspond to Type B2 vessels in the JES classification, remains insufficient. Previous retrospective studies have reported improved accuracy by considering additional findings, such as the size and macroscopic type of the Type B2 vessel area, in evaluating tumor invasion depth. Therefore, this study aimed to investigate whether incorporating the size and/or macroscopic type of the Type B2 vessel area improves the diagnostic accuracy of preoperative tumor invasion depth prediction based on the JES classification. METHODS: This multicenter prospective observational study will include patients diagnosed with MM/SM1 esophageal squamous cell carcinoma based on the Type B2 vessels of the JES classification. The tumor invasion depth will be evaluated using both the standard JES classification (standard-depth evaluation) and the JES classification with additional findings (hypothetical-depth evaluation) for the same set of patients. Data from both endoscopic depth evaluations will be electronically collected and stored in a cloud-based database before endoscopic resection or esophagectomy. This study's primary endpoint is accuracy, defined as the proportion of cases in which the preoperative depth diagnosis matched the histological depth diagnosis after resection. Outcomes of standard- and hypothetical-depth evaluation will be compared. DISCUSSION: Collecting reliable prospective data on the JES classification, explicitly concerning the B2 vessel category, has the potential to provide valuable insights. Incorporating additional findings into the in-depth evaluation process may guide clinical decision-making and promote evidence-based medicine practices in managing superficial esophageal cancer. TRIAL REGISTRATION: This trial was registered in the Clinical Trials Registry of the University Hospital Medical Information Network (UMIN-CTR) under the identifier UMIN000051145, registered on 23/5/2023.

Small gastric synovial sarcoma diagnosed and treatment by laparoscopic-endoscopic cooperative surgery: a case report.

We report a case of small gastric synovial sarcoma (SS) finally diagnosed after laparoscopic-endoscopic cooperative surgery (LECS). A 50 year-old male underwent medical examination for a chief complaint of epigastric pain. Endoscopic examination showed a 20 mm submucosal tumor (SMT) located in the anterior wall which extended to the lesser curvature of the middle stomach. The biopsy tissue did not yield a definitive diagnosis. During 6 months of follow-up for this lesion suspected to be an inflammatory tumor, neither the shape nor the size of the tumor changed. We performed LECS for both diagnosis and treatment. Histologically, the tumor was composed of fascicles of spindle cells. Immunohistochemically, the tumor cells were focally positive for epithelial membrane antigen, cytokeratin (AE1/AE3) and S100 protein, while being negative for desmin, α-smooth muscle actin, CD34, c-kit and DOG1. The expression of INI1 was reduced. Fluorescence in situ hybridization (FISH) detected SS18 rearrangement. The SMT was diagnosed as primary SS. A SMT measuring < 20 mm might be malignant potential tumor such as SS even if there are no typical malignant findings by endoscopy. Surgical resection should be considered for SMT measuring < 20 mm with atypical findings even in the absence of definitive high-risk features.

Performance evaluation of a computer-aided polyp detection system with artificial intelligence for colonoscopy.

OBJECTIVES: A computer-aided detection (CAD) system was developed to support the detection of colorectal lesions by deep learning using video images of lesions and normal mucosa recorded during colonoscopy. The study's purpose was to evaluate the stand-alone performance of this device under blinded conditions. METHODS: This multicenter prospective observational study was conducted at four Japanese institutions. We used 326 videos of colonoscopies recorded with patient consent at institutions in which the Ethics Committees approved the study. The sensitivity of successful detection of the CAD system was calculated using the target lesions, which were detected by adjudicators from two facilities for each lesion appearance frame; inconsistencies were settled by consensus. Successful detection was defined as display of the detection flag on the lesion for more than 0.5 s within 3 s of appearance. RESULTS: Of the 556 target lesions from 185 cases, detection success sensitivity was 97.5% (95% confidence interval [CI] 95.8-98.5%). The "successful detection sensitivity per colonoscopy" was 93% (95% CI 88.3-95.8%). For the frame-based sensitivity, specificity, positive predictive value, and negative predictive value were 86.6% (95% CI 84.8-88.4%), 84.7% (95% CI 83.8-85.6%), 34.9% (95% CI 32.3-37.4%), and 98.2% (95% CI 97.8-98.5%), respectively. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN000044622).

A discrimination model by machine learning to avoid gastrectomy for early gastric cancer.

Aim: Gastrectomy is recommended for patients with early gastric cancer (EGC) because the possibility of lymph node metastasis (LNM) cannot be completely denied. The aim of this study was to develop a discrimination model to select patients who do not require surgery using machine learning. Methods: Data from 382 patients who received gastrectomy for gastric cancer and who were diagnosed with pT1b were extracted for developing a discrimination model. For the validation of this discrimination model, data from 140 consecutive patients who underwent endoscopic resection followed by gastrectomy, with a diagnosis of pT1b EGC, were extracted. We applied XGBoost to develop a discrimination model for clinical and pathological variables. The performance of the discrimination model was evaluated based on the number of cases classified as true negatives for LNM, with no false negatives for LNM allowed. Results: Lymph node metastasis was observed in 95 patients (25%) in the development cohort and 11 patients (8%) in the validation cohort. The discrimination model was developed to identify 27 (7%) patients with no indications for additional surgery due to the prediction of an LNM-negative status with no false negatives. In the validation cohort, 13 (9%) patients were identified as having no indications for additional surgery and no patients with LNM were classified into this group. Conclusion: The discrimination model using XGBoost algorithms could select patients with no risk of LNM from patients with pT1b EGC. This discrimination model was considered promising for clinical decision-making in relation to patients with EGC.

Complications of endoscopic resection in the upper gastrointestinal tract.

Endoscopic resection (ER) is widely utilized as a minimally invasive treatment for upper gastrointestinal tumors; however, complications could occur during and after the procedure. Post-ER mucosal defect leads to delayed perforation and bleeding; therefore, endoscopic closure methods (endoscopic hand-suturing, the endoloop and endoclip closure method, and over-the-scope clip method) and tissue shielding methods (polyglycolic acid sheets and fibrin glue) are developed to prevent these complications. During duodenal ER, complete closure of the mucosal defect significantly reduces delayed bleeding and should be performed. An extensive mucosal defect that comprises three-quarters of the circumference in the esophagus, gastric antrum, or cardia is a significant risk factor for post-ER stricture. Steroid therapy is considered the first-line option for the prevention of esophageal stricture, but its efficacy for gastric stricture remains unclear. Methods for the prevention and management of ER-related complications in the esophagus, stomach, and duodenum differ according to the organ; therefore, endoscopists should be familiar with ways of preventing and managing organ-specific complications.

Clinical and endoscopic features of metachronous gastric cancer with possible lymph node metastasis after endoscopic submucosal dissection and Helicobacter pylori eradication.

BACKGROUND: Several studies have reported the metachronous gastric cancers (MGCs) with possible lymph node metastasis (LNM) after endoscopic submucosal dissection (ESD) and Helicobacter pylori (H. pylori) eradication in which a curative ESD had not been achieved. There have been no published reports of evaluations of the features of patients with MGC with possible LNM after ESD and H. pylori eradication. METHODS: We identified 264 patients with 369 MGCs after H. pylori eradication among the 4354 patients with 5059 early gastric cancers (EGCs) who underwent ESD between 1999 and 2017 and divided them into two groups: patients with MGCs with possible LNM (Group I) and patients with MGCs undergone curative ESD (Group II). We retrospectively compared the features of patients with MGCs and patients with EGCs at index ESD in the two groups. RESULT: Group I consisted of 20 patients with 21 MGCs, and Group II consisted of 244 patients with 348 MGCs. Group I lesions were significantly more common in the posterior wall than in the lesser curvature (odds ratio [OR] = 3.97; 95% confidence intervals [CI] 1.20-13.10). Development of Group I was significantly more common in patients with a body mass index (BMI) < 19.0 kg/m2 than in patients with a BMI ≥ 19.0 kg/m2 at index ESD (OR = 4.44; 95% CI 1.30-15.20). CONCLUSIONS: During surveillance endoscopy after gastric ESD and H. pylori eradication, the posterior wall should be carefully examined to detect MGCs early. Lower BMI may be associated with the development of MGCs with possible LNM.

Oncologic significance of lymphovascular invasion in patients with superficial esophageal squamous cell carcinoma reaching the muscularis mucosae or with slight invasion of the submucosa.

BACKGROUND: The clinicopathological features and the distribution of lymph node metastasis in patients with T1a-MM and T1b-SM1 superficial esophageal squamous cell carcinoma remain unclear; therefore, the optimal treatment strategy is still controversial. METHODS: One hundred and ninety-one patients who had undergone a thoracic esophagectomy with 3-field lymphadenectomy and who were pathologically confirmed to have thoracic superficial esophageal squamous cell carcinoma that had reached the T1a-MM or T1b-SM1 stage were retrospectively reviewed. Risk factors of lymph node metastasis, the distribution of lymph node metastasis, and long-term outcomes were evaluated. RESULTS: A multivariate analysis revealed that lymphovascular invasion was the only independent risk factor of lymph node metastasis (odds ratio: 6.410, P < .001). Patients with primary tumors in the middle thoracic region had lymph node metastasis in all 3 fields, whereas patients with primary tumors in the upper or lower thoracic region did not have distant lymph node metastasis. The frequencies of neck (P = .045) and abdominal (P < .001) lymph node metastasis were significantly higher in lymphovascular invasion-positive patients than those in lymphovascular invasion-negative patients in all cohort. MM/lymphovascular invasion-positive patients with middle thoracic tumors had lymph node metastasis spread from the neck to the abdomen. SM1/lymphovascular invasion-negative patients with middle thoracic tumors did not have lymph node metastasis in the abdominal region. The SM1/pN+ group had a significantly poorer overall survival and relapse-free survival than the other groups. CONCLUSION: The present study revealed that lymphovascular invasion was associated with not only the frequency of lymph node metastasis, but also the distribution of lymph node metastasis. It also suggested that superficial esophageal squamous cell carcinoma patients with T1b-SM1 and lymph node metastasis had a significantly poorer outcome than those with T1a-MM and lymph node metastasis.

Endoscopic Resection of Undifferentiated Early Gastric Cancer.

Endoscopic resection (ER) is widely performed for early gastric cancer (EGC) with a negligible risk of lymph node metastasis (LNM) in Eastern Asian countries. In particular, endoscopic submucosal dissection (ESD) leads to a high en bloc resection rate, enabling accurate pathological evaluation. As undifferentiated EGC (UD-EGC) is known to result in a higher incidence of LNM and infiltrative growth than differentiated EGC (D-EGC), the indications for ER are limited compared with those for D-EGC. Previously, clinical staging as intramucosal UD-EGC ≤2 cm, without ulceration, was presented as 'weakly recommended' or 'expanded indications' for ER in the guidelines of the United States, Europe, Korea, and Japan. Based on promising long-term outcomes from a prospective multicenter study by the Japan Clinical Oncology Group (JCOG) 1009/1010, the status of this indication has expanded and is now considered 'absolute indications' in the latest Japanese guidelines published in 2021. In this study, which comprised 275 patients with UD-EGC (cT1a, ≤2 cm, without ulceration) treated with ESD, the 5-year overall survival (OS) was 99.3% (95% confidence interval, 97.1%-99.8%), which was higher than the threshold 5-year OS (89.9%). Currently, the levels of evidence grades and recommendations for ER of UD-EGC differ among Japan, Korea, and Western countries. Therefore, a further discussion is warranted to generalize the indications for ER of UD-EGC in countries besides Japan.

Circularity Is a Potential Noninvasive Diagnostic Indicator to Differentiate Gastric Submucosal Tumors.

BACKGROUND AND AIMS: Noninvasive, imaging diagnosis of gastrointestinal mesenchymal tumors (GIMTs) is still difficult. This study aimed to develop a novel diagnostic method of GIMTs via endoscopic ultrasonography (EUS) using circularity. METHODS: In a derivation series, we retrospectively collected 50 GIMTs 2-5 cm in diameter of two institutions. After selecting one EUS still image showing the maximal area per lesion, two endoscopists who were blind to the histological diagnosis assessed circularity, a surrogate indicator of roundness (range, 0-1; 1 = a true circle), with an image-analyzing software. Median circularity of three types of GIMT was compared, and the cutoff value to differentiate a group from other groups was presented by drawing a receiver operating characteristic curve. Subsequently, we assessed the diagnostic ability of circularity in 91 GIMTs which were retrospectively collected from the other two institutions by using the optimal cutoff value presented in the derivation series. RESULTS: The circularity in leiomyomas indicated 0.70 and was significantly lower than that of gastrointestinal stromal tumors (0.89), schwannomas (0.90), and their combined group. When leiomyomas were diagnosed as the circularity of <0.8305, which was presented as the optimal cutoff value, the diagnostic accuracy, sensitivity, and specificity in the validation series were 73.6%, 80.0%, and 72.4%, respectively. CONCLUSION: The data demonstrated that leiomyomas significantly exhibited more distortion than other GIMTs. That implies that the difference in shape, which is objectively determined as circularity, is useful to noninvasively discriminate leiomyomas from other GIMTs.

Endoscopic resection of esophageal squamous cell carcinoma: Current indications and treatment outcomes.

Endoscopic resection (ER) is an alternate minimally invasive treatment for superficial esophageal squamous cell carcinoma (SESCC). We aimed to review the clinical indications and treatment outcomes of ER for SESCC. Endoscopic mucosal resection is relatively easy and efficient for SESCC ≤ 15 mm. In contrast, endoscopic submucosal dissection (ESD) is recommended to achieve en bloc resection for lesions >15 mm, in view of the accurate pathological evaluation. The Japan Gastroenterological Endoscopy Society guidelines recommend ER for non-circumferential cT1a-EP/LPM (epithelium/lamina propria mucosae), cT1a-MM/T1b-SM1 (muscularis mucosa/superficial submucosa ≤ 200µm) SESCC, and whole-circumferential T1a-EP/LPM SESCC ≤ 50 mm (upon implementing preventive measures for stenosis), considering the risk-benefit balance of ER. It defines pT1a-EP/LPM without lymphovascular invasion as a curative endoscopic resection. The guidelines recommend additional esophagectomy or chemoradiotherapy for pT1b SESCC or any SESCC, with lymphovascular invasion. However, there is no recommendation for or against the administration of additional treatments for pT1a-MM without lymphovascular invasion, owing to limited evidence. Researchers have reported on high en bloc and R0 resection rates of ESD, and a randomized controlled trial demonstrated that clip-line traction-assisted ESD could significantly reduce the ESD procedural time. Moreover, steroid treatment has been developed to prevent post-ESD esophageal strictures. There have been reports on favorable long-term outcomes of ESD. However, most of them are retrospective studies. Further robust data in prospective trials are warranted to achieve a definitive evidence of ESD, which will be beneficial to patients with SESCC.

Visibility of early gastric cancer in texture and color enhancement imaging.

Objective: There are little data regarding the efficacy of texture and color enhancement imaging (TXI) for early gastric cancer (EGC) diagnosis. This study aimed to compare the color difference and visibility of EGC between white light imaging (WLI) and TXI. Methods: This study included 20 EGCs of 18 patients undergoing endoscopic submucosal dissection. Still images of EGC in WLI, TXI mode 1 (with color enhancement), and TXI mode 2 (without color enhancement), which were consistent in distance, angle, and air insufflation, were constructed by computer simulation. The center of the lesion, eight equal peripheral points 5 mm outside the lesion, and eight inner points two-thirds of the distance from peripheral points to the EGC lesion center were annotated. Mean color differences (ΔE) of the area between peripheral and inner points per lesion in WLI, TXI mode 1, and TXI mode 2 were analyzed. In addition, four endoscopists independently scored the visibility of EGC images of TXI mode 1 and 2 compared with WLI. Results: Clinicopathological characteristics were as follows: 0-IIa/0-IIb/0-IIc/0-IIa+IIc = 6/1/11/2, reddish/pale = 10/10, differentiated/undifferentiated = 18/2, median tumor size = 13.5 mm. Mean ΔE ± SD = WLI/TXI mode1/TXI mode2 = 10.3 ± 4.7, 15.5 ± 7.8, and 12.7 ± 6.1, respectively. Mean ΔE was significantly higher in TXI mode 1 than in WLI. Visibility (improved/no change/decreased) was 7/13/0 and 4/16/0 in TXI mode 1 and 2, respectively. The visibility was significantly more commonly improved in the macroscopic type 0-IIc or 0-IIb than in 0-IIa or IIa+IIc in TXI mode 1. Conclusions: TXI could improve the visibility of EGC compared with WLI.

Emerging texture and color enhancement imaging in early gastric cancer.

Screening endoscopy improves detection and prognosis of patients with gastric cancer. However, even expert endoscopists can miss early gastric cancer under standard white light imaging. Texture and color enhancement imaging (TXI) is an image-enhanced endoscopy that enhances brightness, surface irregularities such elevation or depression, and subtle color changes. A few image-oriented studies have compared the gastric color differences between neoplastic and peripheral areas under both white light imaging and TXI. The results not only suggested that the overall color differences to be more pronounced in TXI, but also that TXI mode 1 was superior to white light imaging in the visibility of early gastric cancer. Despite the promising results in these initial studies, it is unclear whether the superiority of the image-enhanced endoscopy will translate into an improvement in early gastric cancer detection in real practice. Therefore, large-scale prospective studies are necessary to investigate the efficacy of this new technology in the evaluation of patients undergoing screening endoscopy.

Preclinical Efficacy and Clinical Feasibility of a Novel Aerosol-Exposure Protection Mask for Esophagogastroduodenoscopy.

BACKGROUND/AIMS: This study aimed to assess the efficacy of a novel aerosol-exposure protection (AP) mask in preventing coronavirus disease in healthcare professionals during upper gastrointestinal endoscopy and to evaluate its clinical feasibility. METHODS: In Study 1, three healthy volunteers volitionally coughed with and without the AP mask in a cleanroom. Microparticles were visualized and counted with a specific measurement system and compared with and without the AP mask. In Study 2, 30 patients underwent endoscopic resection with the AP mask covering the face, and the SpO2 was measured throughout the procedure. RESULTS: In Study 1, the median number of microparticles in volunteers 1, 2, and 3 with and without the AP mask was 8.5 and 110.0, 7.0 and 51.5, and 8.0 and 95.0, respectively (p<0.01). Using the AP mask, microparticles were reduced by approximately 92%. The median distances of microparticle scattering without the AP mask were 60, 0, and 68 in volunteers 1, 2, and 3, respectively. In Study 2, the mean SpO2 was 96.3%, and desaturation occurred in three patients. CONCLUSION: The AP mask could provide protection from aerosol exposure and can be safely used for endoscopy in clinical practice.

Recent Progress and Challenges in the Diagnosis and Treatment of Gastrointestinal Stromal Tumors.

Gastrointestinal stromal tumors (GISTs) are the most frequent malignant mesenchymal tumors in the gastrointestinal tract. The clinical incidence of GISTs is estimated 10/million/year; however, the true incidence is complicated by frequent findings of tiny GISTs, of which the natural history is unknown. The initial work-up with endoscopy and endoscopic ultrasonography plays important roles in the differential diagnosis of GISTs. Surgery is the only modality for the permanent cure of localized GISTs. In terms of safety and prognostic outcomes, laparoscopy is similar to laparotomy for GIST treatment, including tumors larger than 5 cm. GIST progression is driven by mutations in KIT or PDGFRA or by other rare gene alterations, all of which are mutually exclusive. Tyrosine kinase inhibitors (TKIs) are the standard therapy for metastatic/recurrent GISTs. Molecular alterations are the most reliable biomarkers for TKIs and for other drugs, such as NTRK inhibitors. The pathological and genetic diagnosis prior to treatment has been challenging; however, a newly developed endoscopic device may be useful for diagnosis. In the era of precision medicine, cancer genome profiling by targeted gene panel analysis may enable potential targeted therapy even for GISTs without KIT or PDGFRA mutations.