Multicenter prospective randomized controlled clinical trial comparing the pocket-creation method with and without single-clip traction of colonic endoscopic submucosal dissection.

BACKGROUND: The pocket-creation method (PCM) was developed to overcome the technical difficulties of endoscopic submucosal dissection (ESD), although opening the pocket remains challenging. We developed a novel technique of PCM with single-clip traction (PCM-CT), which uses a reopenable clip as a traction device to maintain stability during the procedure. No prospective study has compared the efficacy of PCM-CT and PCM. This study aimed to investigate the effectiveness of PCM-CT vs. PCM in a randomized controlled trial. METHODS: This randomized controlled clinical trial was conducted at four Japanese institutions. Patients with superficial colorectal neoplastic lesions were included following Japanese guidelines for colorectal cancer. Seven moderately experienced endoscopists performed the ESD procedures using either PCM-CT or PCM. RESULTS: 100 patients were enrolled in the study. Compared with PCM, PCM-CT achieved significantly faster mean (SD) dissection speed (21.4 [10.8] vs. 27.0 [14.5] mm2/min [95%CI 0.5 to 10.7], P = 0.03), and reduced the mean procedure time (81.8 [57.9] vs. 64.8 [47.6] minutes [95%CI -38.2 to 4.3], P = 0.12) and pocket-opening time (37.8 [33.0] vs. 30.0 [28.9] minutes [95%CI -20.2 to 4.6], P = 0.22). En bloc and R0 resection rates were not significantly different between the two groups (100% vs. 100%, P >0.99; 100% vs. 96%, P = 0.50, respectively). No significant differences were observed in adverse events between the two groups. CONCLUSION: ESD facilitated by the novel PCM-CT method appeared to be significantly faster than PCM. Both methods achieved high R0 resection rates.

Achalasia phenotypes and prediction of peroral endoscopic myotomy outcomes using machine learning.

OBJECTIVES: High-resolution manometry (HRM) and esophagography are used for achalasia diagnosis; however, achalasia phenotypes combining esophageal motility and morphology are unknown. Moreover, predicting treatment outcomes of peroral endoscopic myotomy (POEM) in treatment-naïve patients remains an unmet need. METHODS: In this multicenter cohort study, we included 1824 treatment-naïve patients diagnosed with achalasia. In total, 1778 patients underwent POEM. Clustering by machine learning was conducted to identify achalasia phenotypes using patients' demographic data, including age, sex, disease duration, body mass index, and HRM/esophagography findings. Machine learning models were developed to predict persistent symptoms (Eckardt score ≥3) and reflux esophagitis (RE) (Los Angeles grades A-D) after POEM. RESULTS: Machine learning identified three achalasia phenotypes: phenotype 1, type I achalasia with a dilated esophagus (n = 676; 37.0%); phenotype 2, type II achalasia with a dilated esophagus (n = 203; 11.1%); and phenotype 3, late-onset type I-III achalasia with a nondilated esophagus (n = 619, 33.9%). Types I and II achalasia in phenotypes 1 and 2 exhibited different clinical characteristics from those in phenotype 3, implying different pathophysiologies within the same HRM diagnosis. A predictive model for persistent symptoms exhibited an area under the curve of 0.70. Pre-POEM Eckardt score ≥6 was the greatest contributing factor for persistent symptoms. The area under the curve for post-POEM RE was 0.61. CONCLUSION: Achalasia phenotypes combining esophageal motility and morphology indicated multiple disease pathophysiologies. Machine learning helped develop an optimal risk stratification model for persistent symptoms with novel insights into treatment resistance factors.

Pancreatitis and cholangitis caused by metallic wire in the duodenal submucosa and muscularis near the papilla: removal by endoscopic submucosal dissection using the pocket-creation method.

Video 1A metalic wire removed by endoscopic submucosal dissection using the pocket-creation method.

Clinical characteristics of absent contractility and ineffective esophageal motility: a multicenter study in Japan.

BACKGROUND AND AIM: Absent contractility (AC) and ineffective esophageal motility (IEM) are esophageal hypomotility disorders diagnosed using high-resolution manometry (HRM). Patient characteristics and disease course of these conditions and differential diagnosis between AC and achalasia are yet to be elucidated. METHODS: A multicenter study involving 10 high-volume hospitals was conducted. Starlet HRM findings were compared between AC and achalasia. Patient characteristics including underlying disorders and disease courses were analyzed in AC and IEM. RESULTS: Fifty-three patients with AC and 92 with IEM were diagnosed, while achalasia was diagnosed in 1784 patients using the Chicago classification v3.0 (CCv3.0). The cut-off integrated relaxation pressure (IRP) value at 15.7 mmHg showed maximum sensitivity (0.80) and specificity (0.87) for differential diagnosis of AC from type I achalasia. While most ACs were based on systemic disorders such as scleroderma (34%) and neuromuscular diseases (8%), 23% were sporadic cases. The symptom severity of AC was not higher than that of IEM. Regarding the diagnosis of IEM, the more stringent CCv4.0 excluded 14.1% of IEM patients than the CCv3.0, although patient characteristics did not change. In patients with the hypomotile esophagus, concomitance of reflux esophagitis was associated with low distal contractile integral and IRP values. AC and IEM transferred between each other, paralleling with the underlying disease course, although no transition to achalasia was observed. CONCLUSION: A successful determination of the optimal cut-off IRP value was achieved using the starlet HRM system to differentiate AC and achalasia. Follow-up HRM is also useful for differentiating AC from achalasia. Symptom severity may depend on underlying diseases instead of hypomotility severity.

The effect of Aspergillus luchuensis pectin methylesterase genes pmeA and pmeB on methanol production in sweet potato shochu.

To reduce the methanol content in sweet potato shochu, we studied the pectin methylesterase genes of the shochu-koji mold Aspergillus luchuensis. We found the following three homologs of pectin methyleseterase in the genome of A. luchuensis: pmeA, pmeB, and pmeC. Using pectin as a substrate, the methanol-producing activity of the recombinant of each gene expressed in A. luchuensis was examined and found to be present in recombinant PmeA and PmeB. Additionally, small-scale fermentation of sweet potato shochu using disruptions of pmeA and pmeA-pmeB in A. luchuensis (∆pmeA and ∆pmeApmeB) resulted in significant reduction of the methanol content. Taken together, we revealed that the A. luchuensis pmeA gene was mainly involved in methanol production in sweet potato shochu.

Impact of linked color imaging and blue laser imaging on the diagnosis of esophageal squamous cell carcinoma in iodine unstained areas.

The pink color sign in iodine unstained areas is useful to differentiate esophageal squamous cell carcinoma (ESCC) from other lesions. However, some ESCCs have obscure color findings which affect the ability of endoscopists to differentiate these lesions and determine the resection line. Using white light imaging (WLI), linked color imaging (LCI) and blue laser imaging (BLI), 40 early ESCCs were retrospectively evaluated using images before and after iodine staining. Visibility scores for ESCC by expert and non-expert endoscopists were compared using these three modalities and color differences measured for malignant lesions and surrounding mucosa. BLI had the highest score and color difference without iodine staining. Each determination with iodine was much higher than without iodine regardless of the modality. With iodine, ESCC mainly appeared pink, purple and green using WLI, LCI and BLI, respectively and visibility scores determined by non-experts and experts were significantly higher for LCI (both p < 0.001) and BLI (p = 0.018 and p < 0.001) than for WLI. The score with LCI was significantly higher than with BLI among non-experts (p = 0.035). With iodine, the color difference using LCI was twice that with WLI and one with BLI was significantly larger than with WLI (p < 0.001). These greater tendencies were found regardless of location, depth of cancer or intensity of pink color using WLI. In conclusion, areas of ESCC unstained by iodine were easily recognized using LCI and BLI. Visibility of these lesions is excellent even by non-expert endoscopists, suggesting that this method is useful to diagnose ESCC and determine the resection line.

Impact of peroral endoscopic myotomy on high-resolution manometry findings and their association with the procedure's outcomes.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is conducted for patients with esophageal motility disorders based on high-resolution manometry (HRM) findings. However, the impact of POEM on HRM findings and the associations between post-POEM HRM and outcomes have not been clarified. METHODS: In a multicenter, observational, cohort study, patients with achalasia treated by POEM received follow-up HRM. Associations between patient characteristics, POEM procedures, and post-POEM HRM findings, including integrated relaxation pressure (IRP) and distal contractile integral (DCI), were investigated. Furthermore, POEM procedure outcomes were compared with post-POEM HRM findings. RESULTS: Of 2171 patients, 151 (7.0%) showed residual high post-POEM IRP (≥26 mm Hg; Starlet [Starmedical Ltd, Tokyo, Japan]). In a multivariate analysis, high pre-POEM IRPs (odds ratio [OR], 24.3) and gastric myotomy >2 cm (OR, .22) were found to be positive and negative predictive factors of high post-POEM IRPs, respectively. Peristalsis recovery (DCI ≥500 mm Hg/cm/s, at least 1 swallow; Starlet) was visible in 121 of 618 patients (19.6%) who had type II to III achalasia. High pre-POEM IRP (OR, 2.65) and DCI ≥500 (OR, 2.98) predicted peristalsis recovery, whereas esophageal dilation (OR, .42) predicted a risk of no recovery. Extended myotomy did not reveal a significant impact on peristalsis recovery. High or low post-POEM IRP and DCI did not increase the incidence of clinical failure, reflux esophagitis, or symptomatic GERD. CONCLUSIONS: Extended gastric myotomy decreased IRP values, whereas peristalsis recovery depended on the characteristics of achalasia. A residual high post-POEM IRP does not necessarily mean clinical failure. Routine HRM follow-up is not recommended after POEM.

Risk scoring system for the preprocedural prediction of the clinical failure of peroral endoscopic myotomy: a multicenter case-control study.

BACKGROUND: Peroral endoscopic myotomy (POEM) is effective for the management of achalasia and its variants; however, it can be ineffective in some patients. We aimed to develop and validate a risk scoring system to predict the clinical failure of POEM preoperatively. METHODS: Consecutive patients who underwent POEM in 14 high volume centers between 2010 and 2020 were enrolled in this study. Clinical failure was defined as an Eckardt score of ≥ 4 or retreatment. A risk scoring system to predict the short-term clinical failure of POEM was developed using multivariable logistic regression and internally validated using bootstrapping and decision curve analysis. RESULTS: Of the 2740 study patients, 112 (4.1 %) experienced clinical failure 6 months after POEM. Risk scores were assigned for three preoperative factors as follows: preoperative Eckardt score (1 point), manometric diagnosis (-4 points for type II achalasia), and a history of prior treatments (1 point for pneumatic dilation or 12 points for surgical/endoscopic myotomy). The discriminative capacity (concordance statistics 0.68, 95 %CI 0.62-0.72) and calibration (slope 1.15, 95 %CI 0.87-1.40) were shown. Decision curve analysis demonstrated its clinical usefulness. Patients were categorized into low (0-8 points; estimated risk of clinical failure < 5 %) and high risk (9-22 points; ≥ 5 %) groups. The proportions of clinical failure for the categories were stratified according to the mid-term outcomes (log-rank test, P < 0.001). CONCLUSIONS: This risk scoring system can predict the clinical failure of POEM preoperatively and provide useful information when making treatment decisions.

Feasibility of progressive polyp contraction with underwater endoscopic mucosal resection in ≥ 20 mm superficial colorectal lesions.

Background and study aims Underwater endoscopic mucosal resection (UEMR) does not always result in en bloc resection of large colorectal lesions. The aim of this study was to demonstrate the feasibility of en bloc resection with progressive polyp contraction with underwater endoscopic mucosal resection (PP-CUE) of large, superficial colorectal lesions. The advantage of PP-CUE is to enable resection of a superficial non-polypoid lesion that is larger than the snare diameter. Patients and methods Eleven consecutive lesions in ten patients who underwent UEMR with PP-CUE of large superficial colorectal lesions (20 mm or greater) were included. Results The median lesion diameter was 24 mm (interquartile range [IQR], 20-24 mm). All lesions were larger than the 15-mm rotatable snare that was used. Median procedure time and PP-CUE time were 11 minutes (IQR, 8.5-12.3) and 2.3 minutes (IQR, 1.9-3.4), respectively. Pathological diagnoses of resected specimens included six adenomas, three sessile serrated lesions, and two slightly invasive submucosal carcinomas. En bloc and R0 resection rates were both 91 % (10/11). No adverse events occurred. Conclusions PP-CUE is useful to resect superficial non-polypoid colorectal lesions 20 to 25 mm in diameter in an en bloc fashion.

Subtype of Achalasia and Integrated Relaxation Pressure Measured Using the Starlet High-resolution Manometry System: A Multicenter Study in Japan.

Background/Aims: ManoScan and Sandhill high-resolution manometry (HRM) systems are used worldwide; however, the diagnosis of achalasia on the Starlet HRM system is not fully characterized. Furthermore, the impact of calcium channel blockers and nitrites in treating achalasia has not been investigated using HRM. Management of recurrent cases is a priority issue, although few studies have examined patient characteristics. Methods: We conducted a multicenter, large-scale database analysis. First, the diagnosis of treatment-naive achalasia in each HRM system was investigated. Next, patient characteristics were compared between type I-III achalasia, and the impact of patient characteristics, including calcium channel blocker and nitrite use for integrated relaxation pressure (IRP) values, were analyzed. Finally, patient characteristics with recurrent achalasia were elucidated. Results: The frequency of type I achalasia with Starlet was significantly higher than that with ManoScan and Sandhill HRM systems. In achalasia, multivariate analysis identified male sex, advanced age, long disease duration, obesity, type I achalasia, and sigmoid type as risk factors related to normal IRP values (< 26 mmHg). Calcium channel blockers and nitrites use had no significant impact on the IRP values, although achalasia symptoms were indicated to be alleviated. In recurrent cases, the IRP value was significantly lower, and advanced age, long disease duration, and sigmoid type were more common than in treatment-naive patients. Conclusions: We should cautiously interpret the type of achalasia and IRP values in the Starlet HRM system. Symptoms of recurrent cases are related to disease progression rather than IRP values, which should be considered in decision making.

Genetic architecture of berry aroma compounds in a QTL (quantitative trait loci) mapping population of interspecific hybrid grapes (Vitis labruscana × Vitis vinifera).

BACKGROUND: Although grapes accumulate diverse groups of volatile compounds, their genetic regulation in different cultivars remains unelucidated. Therefore, this study investigated the volatile composition in the berries of an interspecific hybrid population from a Vitis labruscana 'Campbell Early' (CE) × Vitis vinifera 'Muscat of Alexandria' (MA) cross to understand the relationship among volatile compounds and their genetic regulation. Then, a quantitative trait locus (QTL) analysis of its volatile compounds was conducted. RESULTS: While MA contained higher concentrations of monoterpenes and norisoprenoids, CE contained higher concentrations of C6 compounds, lactones and shikimic acid derivatives, including volatiles characteristic to American hybrids, i.e., methyl anthranilate, o-aminoacetophenone and mesifurane. Furthermore, a cluster analysis of volatile profiles in the hybrid population discovered ten coordinately modulated free and bound volatile clusters. QTL analysis identified a major QTL on linkage group (LG) 5 in the MA map for 14 monoterpene concentrations, consistent with a previously reported locus. Additionally, several QTLs detected in the CE map affected the concentrations of specific monoterpenes, such as linalool, citronellol and 1,8-cineol, modifying the monoterpene composition in the berries. As for the concentrations of five norisoprenoids, a major common QTL on LG2 was discovered first in this study. Several QTLs with minor effects were also discovered in various volatile groups, such as lactones, alcohols and shikimic acid derivatives. CONCLUSIONS: An overview of the profiles of aroma compounds and their underlying QTLs in a population of interspecific hybrid grapes in which muscat flavor compounds and many other aroma compounds were mixed variously were elucidated. Coordinate modulation of the volatile clusters in the hybrid population suggested an independent mechanism for controlling the volatiles of each group. Accordingly, specific QTLs with significant effects were observed for terpenoids, norisoprenoids and some volatiles highly contained in CE berries.

Efficacy of peroral endoscopic myotomy for esophageal motility disorders after gastric surgery: Japan Achalasia Multicenter Study.

OBJECTIVES: Patients with esophageal motility disorders (EMDs) including achalasia after gastric surgery have not been thoroughly characterized. Furthermore, the efficacy of peroral endoscopic myotomy (POEM) in this population should be clarified. METHODS: In this retrospective multicenter study of 3707 patients with EMDs, 31 patients (0.8%) had a history of gastric surgery. Patient characteristics and POEM efficacy were compared between patients with and without previous gastric surgery. RESULTS: In patients with EMD after gastric surgery, age at EMD diagnosis was higher (72.0 years), male sex was predominant (90.3%), and the American Society of Anesthesiologists physical status score was higher (≥II, 48.4%). High-resolution manometry (HRM) findings did not reveal significant differences. In patients who underwent gastric surgery, atrophic gastritis was common (80.6%), and gastric cancer was the primary surgical indication (32.3%). Distal gastrectomy was performed in 28 patients (90.3%). POEM was effective (3.3% adverse events; 100% treatment success). The incidence rates of reflux esophagitis (RE) and symptomatic gastroesophageal reflux disease (GERD) were 60.0% and 16.7%, respectively, without significant intergroup differences, and severe RE was not observed in the long-term follow-up. Extended gastric myotomy was a risk factor for RE. CONCLUSION: Patients with gastric surgery often present severe disease manifestations; the surgical indication is mainly gastric cancer. HRM findings can be similarly used for diagnosis in patients with and without gastric surgery. POEM maintains safety and efficacy with acceptable RE and symptomatic GERD rates. To prevent RE, extended myotomy should be avoided.

Improved detection of early gastric cancer with linked color imaging using an ultrathin endoscope: a video-based analysis.

Background and study aims Ultrathin endoscopy causes a minimal gag reflex and has minimal effects on cardiopulmonary function. Linked color imaging (LCI) is useful for detection of malignancies in the digestive tract. The aim of this study was to clarify whether LCI with ultrathin endoscopy facilitates detection of early gastric cancer (EGC) despite its lower resolution compared with high-resolution white light imaging (WLI) with standard endoscopy. Patients and methods This was a retrospective analysis with prospectively collected video, including consecutive 166 cases of EGC or gastric atrophy alone. Ninety seconds of screening video was collected using standard and ultrathin endoscopes with both WLI and LCI for each case. Three expert endoscopists assessed each video and the sensitivity of detecting EGC calculated. Color difference calculations were performed. Results Sensitivities using ultrathin WLI, ultrathin LCI, standard WLI, and standard LCI for the identification of cancer were 66.0 %, 80.3 %, 69.9 %, and 84.0 %, respectively. The color difference between malignant lesions and surrounding mucosa with ultrathin LCI and standard LCI were significantly higher than using ultrathin WLI or standard WLI, supported subjectively by the visibility score. Ultrathin LCI color difference and visibility score were significantly higher than standard WLI. Conclusions LCI with a low-resolution ultrathin endoscope is superior to WLI with a high-resolution standard endoscope for gastric cancer screening. This suggests that the high color contrast between EGC and the surrounding mucosa is more important than high-resolution images.

Risks of refractory chest pain after peroral endoscopic myotomy in achalasia-related esophageal motility disorders: short-term results from a multicenter study in Japan.

BACKGROUND AND AIMS: The etiology of chest pain in achalasia-related esophageal motility disorders and the frequency and risk factors of persistent chest pain after peroral endoscopic myotomy (POEM) remain unclear. METHODS: A multicenter cohort study including 14 hospitals was conducted to elucidate the characteristics of patients with chest pain and the efficacy of POEM. RESULTS: Consecutive cases of achalasia-related esophageal motility disorders included 2294 (64.2%) and 1280 (35.8%) patients with and without chest pain, respectively. Among the 2107 patients with chest pain who underwent POEM, we observed complete remission in 1464 patients (69.5%) and nonremission in 643 patients (30.5%), including a partial response in 619 patients (29.4%) and resistance in 24 patients (1.1%). Multivariate analysis revealed that advanced age (odds ratio [OR], .28), male sex (OR, .70), prior treatment (OR, 1.39), and sigmoid type (OR, .65) were related to the prevalence of chest pain. Long disease duration (OR, .69) and esophageal dilation (OR, .79) were related to decreased severity. POEM improved patients' quality of life that was hindered by chest pain. Early onset (OR, 1.45), advanced age (OR, .58), male sex (OR, .79), prior treatment (OR, 1.37), and posterior myotomy (OR, 1.42) were associated with nonremission after POEM; high-resolution manometry (HRM) findings and myotomy length showed no statistical significance on pain etiology and persistence after POEM. CONCLUSIONS: The prevalence and severity of chest pain were dependent on age, sex, disease duration, prior treatment, and esophageal morphology rather than HRM findings. The efficacy of POEM is satisfactory; however, residual pain was often observed. Excessively long myotomy can be avoided, and anterior myotomy may be recommended.