Comparison of hemostatic ability between spray coagulation and forced coagulation modes in endoscopic submucosal dissection in patients with early gastric neoplasms: a study protocol for multicenter randomized controlled trial (Spray-G trial).

BACKGROUND: Endoscopic submucosal dissection (ESD) is the standard treatment for early gastric neoplasms (EGN). Controlling intraoperative bleeding is crucial for ensuring safe and reliable procedures. ESD using the spray coagulation mode (SCM-ESD) has been developed to control bleeding more effectively than ESD using the conventional forced coagulation mode (FCM-ESD). This study aims to compare the hemostatic efficacies of SCM-ESD and FCM-ESD. METHODS: This multicenter, prospective, parallel, randomized, open-label superiority trial will be conducted in five Japanese institutions. Patients with a preoperative diagnosis of intramucosal EGC will be randomized to undergo either SCM-ESD or FCM-ESD. The primary outcome measure is the completion of ESD with an electrosurgical knife alone, without the use of hemostatic forceps. Secondary outcomes include the number and duration of hemostasis using hemostatic forceps, procedure time, curability, and safety. A total of 130 patients will be enrolled in this study. DISCUSSION: This trial will provide evidence on the hemostatic efficacy of SCM-ESD compared with FCM-ESD in patients with intramucosal EGN, potentially improving the safety and reliability of ESD procedures. TRIAL REGISTRATION: The trial has been registered at the University Hospital Medical Information Network Clinical Trials Registration (UMIN-CTR) as UMIN000040518. The reception number is R000054009.

Negligible procedure-related dissemination risk of mucosal incision-assisted biopsy for gastrointestinal stromal tumors versus endoscopic ultrasound-guided fine-needle aspiration/biopsy.

BACKGROUND: Mucosal incision-assisted biopsy (MIAB) is a valuable alternative to endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNAB) for sampling gastric subepithelial lesions (SELs). This study aimed to evaluate the potential risk of dissemination and impact on postoperative prognosis associated with MIAB, which has not yet been investigated. METHODS: Study 1: A prospective observational study was conducted to examine the presence or absence and growth rate of tumor cells in gastric juice before and after the procedure in patients with SELs who underwent MIAB (n = 25) or EUS-FNAB (n = 22) between September 2018 and August 2021. Study 2: A retrospective study was conducted to examine the impact of MIAB on postoperative prognosis in 107 patients with gastrointestinal stromal tumors diagnosed using MIAB (n = 39) or EUS-FNAB (n = 68) who underwent surgery between January 2001 and July 2020. RESULTS: In study 1, although no tumor cells were observed in gastric juice in MIAB before the procedure, they were observed in 64% of patients after obtaining samples (P < 0.001). In contrast, no tumor cells were observed in the gastric juice in EUS-FNAB before and after the procedure. In study 2, there was no significant difference in 5-year disease-free survival between MIAB (100%) and EUS-FNAB (97.1%) (P = 0.27). CONCLUSION: MIAB is safe, with little impact on postoperative prognosis, although the procedure releases some tumor cells after damaging the SEL's pseudocapsule.

Auxiliary diagnosis of subepithelial lesions by impedance measurement during EUS-guided fine-needle biopsy.

BACKGROUND AND AIMS: EUS-guided FNA/biopsy (EUS-FNA/B) is the citerion standard for diagnosing subepithelial lesions (SELs); however, its diagnostic ability for SELs <20 mm is low. We developed a new diagnostic method to differentiate between GI stromal tumor (GIST) and non-GIST by measuring high-frequency impedance (H-impedance) using an EUS-FNB needle. METHODS: The H-impedance of gastric epithelial neoplasms from 16 cases were measured with a conventional impedance probe to confirm whether H-impedance is clinically useful for assessing cell density (study 1). The H-impedance values of exposed SELs from 25 cases with use of the conventional probe (study 2) and nonexposed SELs from 20 cases with use of the EUS-FNB needle probe (study 3) were measured to determine the diagnostic ability of H-impedance for differentiating GISTs from non-GISTs. RESULTS: H-impedance significantly positively correlated with cell density (P = .030) (study 1). The H-impedance of GIST (99.5) measured with a conventional probe was significantly higher than with those of the muscular layer (82.4) and leiomyoma (89.2) (P < .01) (study 2). The H-impedance of GIST measured with the EUS-FNB needle was also significantly higher than that of leiomyoma (GIST: 80.2 vs leiomyoma, 71.8; P = .015). The diagnostic yield of the impedance method for differentiating GISTs from non-GISTs had 94.4% accuracy, 88.9% sensitivity, 100% specificity, and 0.95 area under the curve. Diagnostic ability was not affected by lesion size (P = .86) (study 3). CONCLUSION: Auxiliary differential diagnosis between gastric GISTs and non-GISTs by the H-impedance measurement during EUS-FNB could be a good option, especially when the lesion is <20 mm.

Hybrid and Conventional Endoscopic Submucosal Dissection for Early Gastric Neoplasms: A Multi-Center Randomized Controlled Trial.

BACKGROUND & AIMS: Hybrid endoscopic submucosal dissection (H-ESD), which incorporates endoscopic submucosal dissection (ESD) with endoscopic mucosal resection, has been developed to make ESD technically easier. This study aimed to determine if H-ESD is superior to conventional ESD (C-ESD) for small early gastric neoplasms (EGNs). METHODS: We conducted a multi-center, prospective, open-label, randomized controlled trial to compare the treatment outcomes of H-ESD and C-ESD (Hybrid-G Trial). Patients with differentiated type intramucosal EGN ≤20 mm in diameter and without ulceration were randomly assigned (1:1) to groups that underwent H-ESD or C-ESD. A single multi-functional snare, SOUTEN (ST1850-20, Kaneka, Medix, Tokyo, Japan), was used for H-ESD. The primary outcome was procedure time. Secondary outcomes included mucosal incision time, time and speed of submucosal dissection, curability, and endoscopic procedural adverse events. RESULTS: A total of 39 and 40 patients underwent H-ESD and C-ESD, respectively. The procedure time of H-ESD was significantly shorter than that of C-ESD (33.16 min vs 62.46 min; H-ESD/C-ESD ratio: 0.53; 95% confidence interval, 0.41-0.69; P < .0001). There was no significant difference in mucosal incision time between the 2 groups; the time and speed of submucosal dissection of H-ESD were significantly shorter than those of C-ESD. No difference was observed between the 2 groups in other outcomes. CONCLUSIONS: H-ESD has significantly shorter procedure time than C-ESD, with high and comparable curability and safety for both H-ESD and C-ESD. H-ESD can be a good option for the endoscopic treatment of small EGNs. (UMIN Clinical Trials Registry, Numbers: UMIN000041244).

Efficacy of ultrasound endoscopy with artificial intelligence for the differential diagnosis of non-gastric gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are common subepithelial lesions (SELs) and require treatment considering their malignant potential. We recently developed an endoscopic ultrasound-based artificial intelligence (EUS-AI) system to differentiate GISTs from non-GISTs in gastric SELs, which were used to train the system. We assessed whether the EUS-AI system designed for diagnosing gastric GISTs could be applied to non-gastric GISTs. Between January 2015 and January 2021, 52 patients with non-gastric SELs (esophagus, n = 15; duodenum, n = 26; colon, n = 11) were enrolled. The ability of EUS-AI to differentiate GISTs from non-GISTs in non-gastric SELs was examined. The accuracy, sensitivity, and specificity of EUS-AI for discriminating GISTs from non-GISTs in non-gastric SELs were 94.4%, 100%, and 86.1%, respectively, with an area under the curve of 0.98 based on the cutoff value set using the Youden index. In the subanalysis, the accuracy, sensitivity, and specificity of EUS-AI were highest in the esophagus (100%, 100%, 100%; duodenum, 96.2%, 100%, 0%; colon, 90.9%, 100%, 0%); the cutoff values were determined using the Youden index or the value determined using stomach cases. The diagnostic accuracy of EUS-AI increased as lesion size increased, regardless of lesion location. EUS-AI based on gastric SELs had good diagnostic ability for non-gastric GISTs.

Comparison of the procedure time differences between hybrid endoscopic submucosal dissection and conventional endoscopic submucosal dissection in patients with early gastric neoplasms: a study protocol for a multi-center randomized controlled trial (Hybrid-G trial).

BACKGROUND: Endoscopic submucosal dissection (ESD) is widely accepted as a local treatment for gastrointestinal tract tumors. As a simplified endoscopic procedure, hybrid ESD (H-ESD) has been performed for colorectal neoplasms in recent times. However, whether H-ESD is superior to conventional ESD (C-ESD) for patients with early gastric neoplasms (EGN) remains unclear. In this trial, we will compare the treatment outcomes of H-ESD and C-ESD. We hypothesize that the procedure time for H-ESD is shorter than that for C-ESD. METHODS: This is an investigator-initiated, multi-center, prospective, randomized, open-label, parallel-group trial to be conducted beginning in August 2020 at nine institutions in Japan. We will determine if H-ESD is superior to C-ESD in terms of procedure time in patients with EGN diagnosed as macroscopically intramucosal (T1a) differentiated carcinoma ≤ 20 mm in diameter without ulcerative findings according to current Japanese gastric cancer treatment guidelines. A total of 82 patients will be recruited and randomly assigned to either the C-ESD or the H-ESD group. The primary outcome is ESD procedure time. Secondary outcomes include mucosal incision, time and speed of submucosal dissection, en bloc resection, complete resection, curability, adverse events related to the ESD procedure, extent of dissection before snaring, volume of injection solution, number and time of hemostasis, thickness of the submucosal layer in the resected specimen, and handover to another operator. The stated sample size was determined based on the primary outcome. According to a previous report comparing the procedure times of C-ESD and H-ESD, we hypothesized that H-ESD would provide a 0.2 reduction in logarithmically concerted procedure time (-37%). We estimated that a total of 82 participants were needed to reach a power of 80% for a t-test with a significance level of 0.05 and considering a 10% dropout. DISCUSSION: This trial will provide high-quality data on the benefits and risks of H-ESD for EGN patients. The results of this study could lead to improved outcomes in patients with EGN undergoing ESD. The results will be presented at national and international meetings and published in peer-reviewed journals. TRIAL REGISTRATION: UMIN-CTR UMIN000041244 . Registered on July 29, 2020.

Is a small-caliber or large-caliber endoscope more suitable for colonic self-expandable metallic stent placement? A randomized controlled study.

OBJECTIVES: The colonic self-expandable metallic stent (C-SEMS) with a 9-French (Fr) delivery system allows for a small-caliber endoscope (SCE) to be used to treat malignant colonic obstruction. Despite the lack of evidence, the SCE has become popular because it is considered easier to insert than the large-caliber endoscope (LCE). We aimed to determine whether the SCE is more suitable than the LCE for C-SEMS placement. METHODS: Between July 2018 and November 2019, 50 consecutive patients who were scheduled to undergo C-SEMS for colon obstruction were recruited in this study. Patients were randomized to the SCE or LCE group. The SCE and LCE were used with 9-Fr and 10-Fr delivery systems, respectively. The primary outcome was the total procedure time. Secondary outcomes were the technical success rate, complication rate, clinical success rate, insertion time, guidewire-passage time, stent-deployment time, and colonic obstruction-scoring-system score. RESULTS: Forty-five patients (SCE group, n = 22; LCE group, n = 23) were analyzed. The procedure time in the LCE group (median, 20.5 min) was significantly (p = 0.024) shorter than that in the SCE group (median, 25.1 min). The insertion time in the LCE group (median, 2.0 min) was significantly (p = 0.0049) shorter than that in the SCE group (median, 6.0 min). A sub-analysis of the procedure difficulties showed that the insertion time in the LCE group (median, 5.0 min) was significantly shorter than that in the SCE group (median, 8.5 min). CONCLUSION: Both LCE and SCE can be used for C-SEMS; however, LCE is more suitable than SCE as it achieved a faster and equally efficacious C-SEMS placement as that of SCE. CLINICAL TRIAL REGISTRATION NUMBER: University Hospital Medical Information Network Clinical Trials Registry (UMIN 32748).

Validation of a claims-based algorithm to identify cases of ulcerative colitis in Japan.

BACKGROUND AND AIM: The prevalence of ulcerative colitis (UC) is increasing in Japan. Validated claims-based definitions are required to investigate the epidemiology of UC and its treatment and disease course in clinical practice. This study aimed to develop a claims-based algorithm for UC in Japan. METHODS: A committee of epidemiologists, gastroenterologists, and internal medicine physicians developed a claims-based definition for UC, based on diagnostic codes and claims for UC treatments, procedures (cytapheresis), or surgery (postoperative claims). Claims data and medical records for a random sample of 200 cases per site at two large tertiary care academic centers in Japan were used to calculate the positive predictive value (PPV) of the algorithm for three gold standards of diagnosis, defined as physician diagnosis in the medical records, adjudicated cases, or registration in the Japanese Intractable Disease Registry (IDR). RESULTS: Overall, 1139 claims-defined UC cases were identified. Among 393 randomly sampled cases (mean age 44; 48% female), 94% had received ≥ 1 systemic treatment (immunosuppressants, tumor necrosis factor inhibitors, corticosteroids, or antidiarrheals), 7% had cytapheresis, and 7% had postoperative claims. When physician diagnosis was used as a gold standard, PPV was 90.6% (95% confidence interval [CI]: 87.7-93.5). PPV with expert adjudication was also 90.6% (95% CI: 87.7-93.5). PPVs with enrollment in the IDR as gold standard were lower at 41.5% (95% CI: 36.6-46.3) due to incomplete case registration. CONCLUSIONS: The claims-based algorithm developed for use in Japan is likely to identify UC cases with high PPV for clinical studies using administrative claims databases.

Involvement of interstitial cells of Cajal in nicotinic acetylcholine receptor-induced relaxation of the porcine lower esophageal sphincter.

The interstitial cells of Cajal (ICCs) play an important role in coordinated gastrointestinal motility. The present study aimed to elucidate whether or how ICCs are involved in the lower esophageal sphincter (LES) relaxation induced by stimulation of the nicotinic acetylcholine receptor. The application of 1,1-dimethyl-4-phenyl-piperazinium (DMPP; a nicotinic acetylcholine receptor agonist) induced a transient relaxation in the circular smooth muscle of the porcine LES. DMPP-induced relaxation was abolished by not only 1 µM tetrodotoxin but also the inhibition of ICC activity by pretreatment with 100 µM carbenoxolone (a gap junction inhibitor), pretreatment with 100 µM CaCCinh-A01 (an anoctamin-1 blocker acting as a calcium-activated chloride channel inhibitor), and pretreatment with Cl--free solution. However, pretreatment with 100 µM Nω-nitro-L-arginine methyl ester had little effect on DMPP-induced relaxation. Furthermore, DMPP-induced relaxation was inhibited by pretreatment with 1 mM suramin, a purinergic P2 receptor antagonist, but not by 1 µM VIP (6-28), a vasoactive intestinal peptide (VIP) receptor antagonist. Stimulation of the purinergic P2 receptor with adenosine triphosphate (ATP) induced relaxation, which was abolished by the inhibition of ICC activity by pretreatment with CaCCinh-A01. In conclusion, membrane hyperpolarization of the ICCs via the activation of anoctamin-1 plays a central role in DMPP-induced relaxation. ATP may be a neurotransmitter for inhibitory enteric neurons, which stimulate the ICCs. The ICCs act as the interface of neurotransmission of nicotinic acetylcholine receptor in order to induce LES relaxation.