Endoscopic Ultrasound Can Differentiate High-Grade Pancreatic Intraepithelial Neoplasia, Small Pancreatic Ductal Adenocarcinoma, and Benign Stenosis.

Background/Aims: High-grade pancreatic intraepithelial neoplasia and invasive pancreatic ductal adenocarcinoma ≤10 mm are targets for early detection of pancreatic cancer. However, their imaging characteristics are unknown. We aimed to identify endoscopic ultrasound findings for the detection of these lesions. Methods: Patients diagnosed with high-grade pancreatic intraepithelial neoplasia (n=29), pancreatic ductal adenocarcinoma ≤10 mm (n=11) (who underwent surgical resection), or benign main pancreatic duct stenosis (n=20) between January 2014 and January 2021 were retrospectively included. Six features differentiating these lesions were examined by endoscopic ultrasonography: main pancreatic duct stenosis, upstream main pancreatic duct dilation, hypoechoic areas surrounding the main pancreatic duct irregularities (mottled areas without demarcation or round areas with demarcation), branch duct dilation, prominent lobular segmentation, and atrophy. Interobserver agreement was assessed by two independent observers. Results: Hypoechoic areas surrounding the main pancreatic duct irregularities were observed more frequently in high-grade pancreatic intraepithelial neoplasia (82.8%) and pancreatic ductal adenocarcinoma ≤10 mm (90.9%) than in benign stenosis (15.0%) (p<0.001). High-grade pancreatic intraepithelial neoplasia exhibited mottled hypoechoic areas more frequently (79.3% vs 18.9%, p<0.001), and round hypoechoic areas less frequently (3.4% vs 72.7%, p<0.001), than pancreatic ductal adenocarcinoma ≤10 mm. The sensitivity and specificity of hypoechoic areas for differentiating high-grade pancreatic intraepithelial neoplasia, pancreatic ductal adenocarcinoma ≤10 mm, and benign stenosis were both 85.0%, with moderate interobserver agreement. Conclusions: The hypoechoic areas surrounding main pancreatic duct irregularities on endoscopic ultrasound may differentiate between high-grade pancreatic intraepithelial neoplasia, pancreatic ductal adenocarcinoma ≤10 mm, and benign stenosis (Trial Registration: UMIN Clinical Trials Registry (UMIN000044789).

Efficacy of the Castor Oil-Filled Capsule Method as Preparation for Colon Capsule Endoscopy.

BACKGROUND: Colon capsule endoscopy (CCE) is useful as an alternative examination for patients in whom colonoscopy is difficult. The Japanese Association for Capsule Endoscopy has published a recommended regimen for CCE using castor oil, which is becoming a standard examination method for CCE in Japan. However, castor oil has an unpleasant flavor. Therefore, patient acceptance is not good. OBJECTIVES: The aims were to develop a castor oil-filled capsule and evaluate its feasibility and patient acceptance in a retrospective, comparative study. METHOD: A dissolution study of pig-derived gelatin capsules filled with castor oil was performed using artificial gastric juice. The CCE excretion rates within battery lifetime, CCE examination times, endoscopic colonic cleansing levels, and patient acceptability between CCE boosters with a castor oil-filled capsule and without castor oil were retrospectively compared using medical information, clinical data, and endoscopic findings at Takada Chuo Hospital from September 2016 to August 2019. RESULTS: The castor oil-filled capsules were completely disintegrated at approximately 1-3 min in artificial gastric juice. Bowel preparation with oil-filled capsules and without castor oil was performed in 27 and 24 patients, respectively. CCE excretion rates within battery life were 100% and 91.7% (p = 0.217), small bowel transit times were 115 min and 143 min (p = 0.046), colon transit times were 168 min and 148 min (p = 0.733), and adequate colonic cleansing rates were 85.2% and 86.3% (p = 1.000) in patients using bowel preparation with and without oil-filled capsules, respectively. Regarding acceptance, the taste was not problematic in 85.2%, and tolerability for the next CCE was 96.3%. CONCLUSIONS: CCE using a castor oil-filled capsule method achieved high examination performance and sufficient patient tolerability.

Endoscopic finding of hematin represents strong gastric acidity.

Background: Hematin is a state in which hemoglobin, as petechiae, is discolored to a brown coffee color by gastric hydrochloric acid. Given the nature of hematin, a close relationship between hematin and acidity has been suggested, but has not been confirmed. We investigated the clinical significance of endoscopic finding of hematin with respect to gastric acidity. Methods: A total of 501 patients were assessed for both hematin and fasting gastric juice pH by endoscopy. Endpoints were as follows: 1) the relationship between the presence of hematin and the fasting gastric juice pH; and 2) the diagnostic performance of endoscopic hematin. In addition, we performed a supplementary in vitro study to clarify the relationship between hematin formation and various acid pH levels. Results: The prevalence of hematin was 31.1% (142/206), 4.6% (5/109) and 45.2% (84/186) in the H. pylori-uninfected, -infected and -eradicated groups, respectively. The mean pH of fasting gastric juice in the hematin-positive cases was significantly lower than the hematin-negative cases (mean pH 1.2, 95% confidence interval [CI] 1.1-1.3 vs. 2.7 95%CI 2.5-3.0; P<0.001). The sensitivity, specificity, positive predictive value and negative predictive value of hematin for predicting strong acidic condition (pH 1 or 2 for fasting gastric juice) were 36.0%, 98.1%, 98.7% and 29.3%, respectively. Interobserver agreement was categorized as "excellent" (k=0.88). Supplementary in vitro results showed that hematin formation was only observed at a pH=1. Conclusion: Endoscopic finding of hematin represent strong gastric acidity.

Examine the Availability and Safety of Mucosal Cutting Biopsy Technique for Diagnosis of Gastric Submucosal Tumor.

OBJECTIVES: Differentiating gastrointestinal stromal tumor (GIST) from other submucosal tumors (SMTs) is important in diagnosing SMT. GIST is an immunohistological diagnosis that cannot be made from images alone. Tissue sampling of tumor sites is thus becoming increasingly important. In this study, the utility and associated complications of mucosal cutting biopsy (MCB) for gastric SMTs were investigated. METHODS: This was a case series study. The subjects were patients aged ≥20 years old in whom an SMT was seen on esophagogastroduodenography and who underwent MCB between January 2012 and December 2016. Patient information, endoscopy findings, gastric SMT size, pathological diagnosis, and other information were gathered from medical records. The SMT size was the maximum diameter that could be visualized on EUS. The pathological diagnosis was made with hematoxylin-eosin staining, with immunostaining added to diagnose GIST. The endpoint was the histopathological diagnostic yield. Risk assessment using the Miettinen classification and modified Fletcher classification was also done for GISTs treated with surgery. RESULTS: The mean tumor diameter was 15.4 mm. The tumor diameter was ≥20 mm in seven patients and <20 mm in 23 patients. The tissue-acquiring rate was 93.3%. A histological diagnosis could not be made in two patients. The only complication was that bleeding required endoscopic hemostasis during the procedure in one patient, but no subsequent bleeding or no postoperative bleeding was seen. CONCLUSIONS: MCB is an appropriate and safe procedure in the diagnosis of gastric SMTs. Many hospitals will be able to perform MCB if they have the environment, including skills and equipment, to perform endoscopic submucosal dissection.

Thermal stabilization of penicillolysin, a thermolabile 19 kDa Zn2+-protease, obtained by site-directed mutagenesis.

Penicillolysin is a member of the clan MX and the family of M35 proteases. The enzyme is a thermolabile Zn(2+)- protease from Penicillium citrinum with a unique substrate profile. We expressed recombinant penicillolysin in Aspergillus oryzae and generated several site-directed mutants, R33E/E60R, A167E and T81P, with the intention of exploring thermal stabilization of this protein. We based our choice of mutations on the structures of homologous thermally stable enzymes, deuterolysin (EC 3.4.24.39) from A.oryzae and a peptidyl-Lys metallopeptidase (GfMEP) from the edible mushroom Grifora frondsa. The resulting mutant proteins exhibited comparable catalytic efficiency to the wild-type enzyme and some showed a higher tolerance to temperature.