Background: The potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene has recently received much attention as a candidate susceptibility gene for type 2 diabetes mellitus, especially in Asian populations. We previously reported that Kcnq1 mutant mice exhibit reduced insulin secretion and hyperglycemia due to a decrease in pancreatic β-cell mass. Through in vivo and in vitro analyses, we ascertained that this mechanism is the result of the downregulation of the non-coding RNA ‘Kcnq1ot1,’ which is expressed in the paternal allele of the Kcnq1 gene region, causing an increase in the expression of the cell cycle inhibitor cyclin dependent kinase inhibitor 1C (Cdkn1c). It was found that decreased Kcnq1ot1 expression resulted in pancreatic β-cell failure; however, the degree of pancreatic β-cell volume reduction was not severe. Methods: We induced obesity in Kcnq1ot1 truncation mice by feeding them a high-fat diet and evaluated pancreatic β-cell mass. Results: In the present study, we reveal that CCAAT/enhancer binding protein beta (C/EBPβ), which is expressed at higher levels in pancreatic β-cells in obese individuals, further increases the expression of Cdkn1c, which is upregulated by the Kcnq1 gene mutation. We found that simultaneous Cdkn1c hypomethylation and C/EBPβ overexpression in pancreatic β-cells causes a synergistic decrease in pancreatic β-cell mass. Conclusion This finding suggests that the synergistic effect of genetic factors such as Kcnq1 gene mutations and environmental factors such as obesity and overeating, which lead to increased expression of C/EBPβ, contribute to the regulation of pancreatic β-cell mass. This study is the first to show that the Kcnq1 gene is related to pancreatic β-cell mass through genetic-environment interactions.

Background/Aims: Selective bile duct or pancreatic duct cannulation remains a significant initial hurdle in endoscopic retrograde cholangiopancreatography (ERCP) despite advances in endoscopy and accessories. This study evaluated our experience with a rotatable sphincterotome in cases of difficult cannulation. Methods: We retrospectively reviewed ERCP cases using TRUEtome, a rotatable sphincterotome, as a rescue device for cannulation at a cancer institute in Japan from October 2014 to December 2021. Results: TRUEtome was used in 88 patients. Duodenoscopes were used for 51 patients, while single-balloon enteroscopes (SBE) were used for 37 patients. TRUEtome was used for biliary and pancreatic duct cannulation (84.1%), intrahepatic bile duct selection (12.5%), and strictures of the afferent limb (3.4%). Cannulation success rates were similar in the duodenoscope and SBE groups (86.3% vs. 75.7%, p=0.213). TRUEtome was more commonly used in cases with steep cannulation angles in the duodenoscope group and in cases requiring cannulation in different directions in the SBE group. There were no significant differences in adverse events between the two groups. Conclusions The cannulation sphincterotome was useful for difficult cannulations in both unaltered and surgically altered anatomies. It may be an option to consider before high-risk procedures such as precut and endoscopic ultrasound-guided rendezvous techniques.

Background/Aims: The optimal length of the uncovered portion of partially covered self-expandable metal stents (PCSEMSs) used in endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) remains unclear. This study investigated the safety and efficacy of PCSEMSs with different uncovered lengths, with a focus on stent migration and time to recurrent biliary obstruction (RBO). Methods: Outcomes of patients undergoing EUS-HGS using PCSEMSs with 5-mm and 20-mm uncovered portions at our institution from January 2016 to December 2021 were compared. Results: Sixty-two patients underwent EUS-HGS using PCSEMS (5/20-mm uncovered portions: 32/30). Stent migration occurred only in the 5-mm group. There were no differences in RBO rates (28.1% vs. 40.0%) or median time to RBO (6.8 vs. 7.1 months) between the two groups. Median overall survival (OS) was longer in the 20-mm group (3.1 vs. 4.9 months, p=0.037) due to the higher number of patients that resumed chemotherapy after EUS-HGS (56.7% vs. 28.1%, p=0.029). Good performance status, absence of hepatic metastases, and chemotherapy after EUS-HGS were independent predictors of longer OS. Conclusions No migration was observed in patients treated with PCSEMS with 20-mm uncovered portions. Patients treated with PCSEMS with 20-mm uncovered portions performed at least as well as those treated with 5-mm uncovered portions in all material respects.

Background/Aims: Hepaticojejunostomy anastomotic stricture (HJAS) is a feared adverse event associated with hepatopancreatobiliary surgery. Although balloon dilation for benign HJAS during endoscopic retrograde cholangiopancreatography with balloon-assisted enteroscopy has been reported to be useful, the treatment strategy remains controversial. Therefore, we evaluated the outcomes and risk factors of recurrent stenosis after balloon dilation alone for benign HJAS. Methods: We retrospectively analyzed consecutive patients who underwent balloon-assisted enteroscopy–endoscopic retrograde cholangiopancreatography for benign HJAS at our institution between July 2014 and December 2020. Results: Forty-six patients were included, 16 of whom had recurrent HJAS after balloon dilation. The patency rates at 1 and 2 years after balloon dilation were 76.8% and 64.2%, respectively. Presence of a residual balloon notch during balloon dilation was an independent predictor of recurrence (hazard ratio, 2.80; 95% confidence interval, 1.01–7.78; p=0.048), whereas HJAS within postoperative 1 year tended to be associated with recurrence (hazard ratio, 2.43; 95% confidence interval, 0.85–6.89; p=0.096). The patency rates in patients without a residual balloon notch were 82.1% and 73.1% after 1 and 2 years, respectively. Conclusions Balloon dilation alone may be a viable option for patients with benign HJAS without residual balloon notches on fluoroscopy.

Background/Aims: Digital single-operator cholangioscopy (DSOC)-guided mapping biopsy (DMB) and tube-assisted mapping biopsy (TMB) are two techniques used for preoperative evaluation of biliary tract cancer (BTC). However, data regarding the diagnostic performance of these techniques are limited. Methods: We retrospectively examined consecutive patients with BTC who underwent either technique at our institution between 2018 and 2020. We evaluated the technical success rate, adequate tissue acquisition rate, and diagnostic performance of these techniques for the evaluation of lateral spread of BTC. Results: A total of 54 patients were included in the study. The technical success rate of reaching the target sites was 95% for DMB and 100% for TMB. The adequate tissue acquisition rate was 61% for DMB and 69% for TMB. The adequate tissue acquisition rate was low, especially for target sites beyond the secondary biliary radicles. The sensitivity of DMB alone was 39%, which improved to 65% when combined with visual impression. Experts demonstrated a higher negative predictive value and diagnostic accuracy with respect to both DSOC visual impression and DMB for the evaluation of lateral spread of BTC compared to trainees. Conclusions Adequate tissue acquisition rates were similar between the two techniques. Since DMB requires expertise, TMB may be an acceptable option when DSOC is unavailable or when DSOC expertise is limited.

Background/Aims: Several fine-needle biopsy (FNB) needles are available for endoscopic ultrasound (EUS)-guided tissue acquisition. However, there is disagreement on which type of needle has the best diagnostic yield. The aim of this study was to compare the performance and safety of two commonly used EUS-FNB needles. Methods: We retrospectively analyzed consecutive patients who underwent EUS-FNB between June 2016 and March 2020 in our hospital. Two types of needles were evaluated: a 20-gauge Menghini needle with a lateral forward bevel and a 22-gauge Franseen needle. Rapid on-site evaluation was performed in all the cases. A multivariate analysis was performed to clarify the negative predictive factors for obtaining a histological diagnosis. Propensity score matching was performed to compare the diagnostic yields of these two needles. Results: We analyzed 666 patients and 690 lesions. The overall diagnostic rate of histology alone was 88.8%, and the overall adverse event rate was 1.5%. Transduodenal access and small lesions (≤2 cm) were identified as negative predictive factors for obtaining a histological diagnosis. After propensity score matching, 482 lesions were analyzed. The diagnostic accuracy rates of histology in the M and F needle groups were 89.2% and 88.8%, respectively (p=1.00). Conclusions Both the needles showed high diagnostic yield, and no significant difference in performance was observed between the two.

Background/Aims: Several fine-needle biopsy (FNB) needles are available for endoscopic ultrasound (EUS)-guided tissue acquisition. However, there is disagreement on which type of needle has the best diagnostic yield. The aim of this study was to compare the performance and safety of two commonly used EUS-FNB needles. Methods: We retrospectively analyzed consecutive patients who underwent EUS-FNB between June 2016 and March 2020 in our hospital. Two types of needles were evaluated: a 20-gauge Menghini needle with a lateral forward bevel and a 22-gauge Franseen needle. Rapid on-site evaluation was performed in all the cases. A multivariate analysis was performed to clarify the negative predictive factors for obtaining a histological diagnosis. Propensity score matching was performed to compare the diagnostic yields of these two needles. Results: We analyzed 666 patients and 690 lesions. The overall diagnostic rate of histology alone was 88.8%, and the overall adverse event rate was 1.5%. Transduodenal access and small lesions (≤2 cm) were identified as negative predictive factors for obtaining a histological diagnosis. After propensity score matching, 482 lesions were analyzed. The diagnostic accuracy rates of histology in the M and F needle groups were 89.2% and 88.8%, respectively (p=1.00). Conclusions Both the needles showed high diagnostic yield, and no significant difference in performance was observed between the two.