Fumisato Sasaki

Background/Objectives: Aldehyde dehydrogenase 2 (ALDH2) detoxifies acetaldehyde, and impaired ALDH2 activity has been implicated in carcinogenesis. The acetaldehyde breath test (ABT) enables noninvasive functional assessment of ALDH2 activity, but its association with pancreatic disease remains unclear. We examined associations between ABT-assessed ALDH2 activity and pancreatic disease outcomes. Methods: This case–control study included 287 health checkup participants, 131 patients with benign pancreatic disease, and 65 patients with pancreatic cancer. Participants underwent ABT, and the acetaldehyde-to-ethanol (A/E) ratio was calculated. The ALDH2 inactive phenotype was defined as an A/E ratio ≥ 23.3. Multinomial logistic regression used health checkup participants as the reference. Results: The median A/E ratio was higher in patients with benign pancreatic disease and pancreatic cancer than in health checkup participants (21.7 and 24.2 vs. 13.6; p < 0.001). The ALDH2 inactive phenotype was associated with benign pancreatic disease (relative risk ratio [RRR], 3.55; 95% confidence interval [CI], 1.85–6.83) and pancreatic cancer (RRR, 4.82; 95% CI, 2.13–10.88). The highest A/E ratio category was also associated with benign pancreatic disease (RRR, 8.77; 95% CI, 3.59–21.39) and pancreatic cancer (RRR, 12.79; 95% CI, 4.41–37.09). Exploratory spline analyses showed associations between higher A/E ratios and pancreatic disease outcomes without clear evidence of nonlinearity. Conclusions: A higher ABT-derived A/E ratio was associated with benign pancreatic disease and pancreatic cancer in this selected case–control study. Prospective studies are needed to determine whether functional assessment of aldehyde metabolism provides clinically useful information for pancreatic disease risk assessment. Trial registration number: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000052609; registered 1 November 2023.

Background/Objectives: Several reports have shown that the hypoattenuation pattern of contrast-enhanced computed tomography (CECT) in pancreatic neuroendocrine tumors (PanNETs) is associated with poor overall survival (OS). However, these studies also included neuroendocrine carcinoma. Therefore, this study retrospectively investigated the relationship between attenuation patterns and OS, specifically in PanNETs. Methods: Between July 2005 and August 2022, 80 consecutive patients (median age, 64 years; 39 males and 41 females) with pathologically confirmed PanNETs were enrolled. Pretreatment factors associated with PanNET prognosis were evaluated. Results: The median tumor diameter was 18 mm (range, 6–150 mm). The PanNET grades were G1 in 45 patients (56%), G2 in 31 (39%), and G3 in 4 (5%). Hyperattenuation and hypoattenuation patterns were observed in 64 (80%) and 16 (20%) patients, respectively. Surgery was performed on 63 patients (79%), and 18 (23%) had distant metastases. Multivariate analysis identified the hypoattenuation pattern on pretreatment CECT as a factor significantly associated with OS in all participants (p < 0.001; hazard ratio [HR], 9.45) and in patients with PanNET G2 (p = 0.007; HR, 9.13). Median OS was longer in the hyperattenuation group than in the hypoattenuation group among all participants (hyperattenuation, not reached; hypoattenuation, 40.1 months; p < 0.001) and among patients with PanNET G2 (hyperattenuation, not reached; hypoattenuation, 36.3 months; p = 0.001). Conclusions: PanNETs with a hypoattenuation pattern on CECT had a worse prognosis than those with hyperattenuation, even among tumors of the same pathological grade (G2).

Delayed bleeding following endoscopic mucosal resection or endoscopic submucosal dissection is a serious concern in patients receiving anticoagulant therapy. We previously established an experimental animal model of delayed gastric bleeding following endoscopic resection under controlled anticoagulation. In this study, we aimed to evaluate the potential preventive effect of hydrophobized microparticles (hMPs), a novel sprayable wound-covering material derived from Alaska pollock gelatin, in preventing delayed bleeding. Twelve gastric mucosal defects were created by endoscopic mucosal resection with ligation in three CLAWN miniature swine. To induce delayed bleeding, systemic heparin was administered after confirming an activated clotting time greater than 220 s. hMPs were endoscopically sprayed into each ulcer base (200 mg/ulcer). Endoscopic examination was performed 24 h later. The primary endpoint was the presence or absence of delayed bleeding. Secondary endpoints included hMP retention, ulcer coverage rate, presence of exposed vessels, and vascular coverage by hMPs. During the 24-hour observation period, no delayed bleeding was observed in any of the three CLAWN miniature swine treated with hMPs. Hemoglobin levels on Day 1 remained stable in all swine. hMPs were present in 100% of the ulcers. Complete ulcer base coverage (100%) was achieved in 55.6% (20/36) of the sections, with ≥ 50% coverage observed in all sections. Exposed vessels were identified in 36.1% (13/36) of ulcers, and all were covered with hMPs. Endoscopic spray application of hMPs demonstrated strong adhesion to gastric ulcers and was associated with the absence of delayed bleeding in this short-term experimental model. These findings suggest that hMPs may represent a promising strategy for reducing the risk of delayed bleeding after gastrointestinal endoscopic surgery.

Objectives: Endoscopic ultrasound‐guided hepaticogastrostomy (EUS‐HGS) is useful in cases of endoscopic retrograde cholangiopancreatography failure. However, the procedure has a high incidence of procedure‐related early adverse events (PRAEs). This study retrospectively evaluated risk factors for such events post‐EUS‐HGS. Methods: This multicenter study included 222 patients (120 males and 102 females; median age = 73 years) who underwent initial EUS‐HGS. The clinical success rate and PRAE incidence, and risk factors were analyzed. PRAEs were defined as AEs occurring within 2 weeks. Results: The median procedure time was 41 min. Metal or plastic stents were used for EUS‐HGS in 107 and 115 patients, respectively. Fistula dilation and concomitant antegrade stenting (AGS) were performed in 166 and 45 patients, respectively. The clinical success rate and PRAE incidence were 85.1% and 22.1%, respectively. Identified PRAEs included acute peritonitis (9.5%), fever (6.8%), abdominal pain (2.3%), and acute pancreatitis (1.4%). Multivariate analysis identified dilation device use ( p = 0.01) and AGS ( p = 0.03) as PRAE risk factors. AGS in patients who underwent fistula dilation ( p = 0.02) and procedure time ≥41 min in those who underwent EUS‐HGS with AGS ( p = 0.01) were PRAE risk factors. Conclusions: Fistula dilation and AGS are associated with an increased risk of PRAEs post‐EUS‐HGS. Careful postoperative follow‐up for such events is required in patients undergoing fistula dilation for EUS‐HGS with AGS and prolonged procedure time.

Background: We aimed to identify an acceptable waiting period between the diagnosis of superficial esophageal squamous cell carcinoma (SESCC) and endoscopic submucosal dissection (ESD). Methods: This retrospective, single-center study included 423 patients with 514 SESCC lesions. All patients underwent image-enhanced magnifying endoscopy at initial evaluation and on the day of ESD. Following three outcomes were assessed: the diagnostic accuracy of tumor invasion depth on the day of ESD using the Japanese Esophageal Society classification; changes in diagnosis between initial and final evaluations across different waiting intervals; and 5-year survival rates based on intrapapillary capillary loop patterns (B1 vs. B2) and waiting duration. Results: The diagnostic accuracy was 96.6% for B1 vessels (EP/LPM), 59.6% for B2 vessels (MM/SM1), and 84.6% for B3 vessels (SM2 or deeper). Among B1 lesions, 100% remained B1 on the day of ESD across all time groups. For B2 lesions, stability was observed in 100% of cases within one month, 98.2% in one to two months, 92.9% in two to three months, and 100% after three months. Five-year survival rates showed no significant differences among waiting period groups in both B1 and B2 categories. Conclusions: A waiting period of 3 months is acceptable for patients with SESCC classified as B1 vessels, provided the diagnostic accuracy is maintained. Thorough endoscopic evaluation supports safe scheduling flexibility without adversely affecting long-term outcomes.

Objectives: Most esophageal cancers in Japan are squamous cell carcinomas; however, there has been some concern regarding a recent increase in Barrett's esophageal adenocarcinoma (BEA). This study aimed to clarify the clinical characteristics and outcomes of patients treated via endoscopic submucosal dissection (ESD) in Kyushu, including changes over time. Methods: This multicenter, retrospective, observational study was conducted among 21 institutes situated in Kyushu. Data from patients who underwent ESD for BEA or esophageal squamous cell carcinoma between January 2010 and December 2023 were extracted from the pathology database and reviewed. Results: The total number of esophageal ESD cases increased from 2299 over the first 7 years to 4009 over the second seven. The incidence of BEA increased from 3.6% (86/2299) over the earlier period to 4.7% (197/4009; p = 0.034) over the latter. We analyzed data from 283 patients (287 lesions). Smaller tumor‐sized lesions were detected over the latter period (14.2 ± 11.6 vs. 11.2 ± 9.5 cm ² , p = 0.022), significantly reducing treatment times (122.1 ± 81.2 vs. 93.2 ± 53.3 min p < 0.001). The procedure was safe, with low incidence rates, over both the earlier and later periods (respectively), of perforation (0% vs. 1.0%), delayed bleeding (1.2% vs. 2.0%), and pneumonia (4.7% vs. 4.6%). Conclusion: The proportion of esophageal ESD procedures to treat BEA has increased in Japan's Kyushu region. This procedure has a comparable safety profile to similar ESD procedures used to treat other conditions.

In Japan, the prevalence of Barrett's esophageal adenocarcinoma (BEA) has recently increased owing to a decrease in the number of patients with Helicobacter pylori infection, westernization of the diet, and an increase in obesity prevalence. However, BEA in patients in their 20s is extremely rare. Our patient was a 20‐year‐old Japanese woman with chief complaints of vomiting and nausea. Esophagogastroduodenoscopy was performed to investigate the cause of vomiting, and a raised lesion was found in the gastroesophageal junctional zone. In the magnified observation, the mucosal pattern of the lesion was partially invisible, and the vascular pattern was irregular; the lesion was diagnosed based on the Japan Esophageal Society classification for Barrett's esophagus ‐related superficial neoplasia. Endocytoscopic observations revealed a highly irregular glandular structure. Computed tomography showed no distant metastasis. Based on these results, we diagnosed BEA as short‐segment Barrett's esophagus and performed an endoscopic submucosal dissection. The pathological diagnosis was pT1a‐DMM. It was a well‐differentiated adenocarcinoma and was treated with curative resection.BEA is extremely rare in young adults in their 20s. Nonetheless, appropriate surveillance is required for patients with multiple risk factors, including obesity and exposure to acid and bile resulting from persistent vomiting.

Background: Esophageal mucosal resection for superficial esophageal cancer can lead to postoperative esophageal stricture, with current preventive measures being insufficient. Sprayable wound dressings containing hydrophobized microparticles exhibit strong adhesion. This study aimed to investigate the preventive effects of hydrophobized microparticles on esophageal stenosis following endoscopic submucosal dissection. Methods: Circumferential esophageal endoscopic submucosal dissection was performed on miniature swine (n = 6). Swine were categorized into two groups: those sprayed with hydrophobized microparticles (sprayed group) and those not sprayed (non-sprayed group). Hydrophobized microparticles were sprayed onto the sprayed group on Days 0, 3, and 7 of endoscopic submucosal dissection. The non-sprayed group underwent endoscopy on the same days. Esophageal stricture rate, submucosal inflammatory cell infiltration, submucosal fibrosis, and thickening of the muscular layer were compared between the groups on Day 14 of endoscopic submucosal dissection. Results: Spraying of hydrophobized microparticles was easily performed using an existing endoscopic spraying device. The esophageal stricture rate was significantly lower in the sprayed group than in the non-sprayed group (76.1% versus 90.6%, p < 0.05). The sprayed group showed suppression of inflammatory cell infiltration in the submucosal layer (p < 0.01) and thickening of the muscular layer (p < 0.01). Conclusions: Sprayable tissue-adhesive hydrophobized microparticles reduce the stricture rate after esophageal ESD by inhibiting inflammatory cell infiltration, submucosal fibrosis, and thickening of the muscular layer. The use of hydrophobized microparticles for preventing post-endoscopic submucosal dissection esophageal stenosis offers a promising avenue for clinical applications in endoscopic procedures, potentially improving patient outcomes.