Safety and efficacy of trans-afferent loop endoscopic ultrasound-guided pancreaticojejunostomy for post pancreaticoduodenectomy anastomotic stricture using the forward-viewing echoendoscope: a retrospective study from Japan.

Background/Aims: Endoscopic ultrasound (EUS)-guided pancreatic duct drainage is a well-established procedure for managing pancreaticojejunostomy anastomotic strictures (PJAS) post-Whipple surgery. In this study, we examined the effectiveness and safety of EUS-guided pancreaticojejunostomy (EUS-PJS). Methods: This retrospective, single-arm study was performed at Aichi Cancer Center Hospital on 10 patients who underwent EUS-guided pancreaticojejunostomy through the afferent jejunal loop using a forward-viewing echoendoscope when endoscopic retrograde pancreatography failed. Our primary endpoint was technical success rate, defined as successful stent insertion. The secondary endpoints were early and late adverse events. Results: A total of 10 patients underwent EUS-PJS between February 2019 and October 2023. The technical success rate was 100%. The median procedure time was 23.5 minutes. No remarkable early or late adverse events related to the procedure, except for fever, occurred in two patients. The median follow-up duration was 9.5 months, and the median number of stent exchanges was two. A stent-free state was achieved in three patients. Conclusions: EUS-PJS for PJAS management after pancreaticoduodenectomy appears to be an effective and safe procedure with the potential advantages of fewer reinterventions and the creation of a permanent drainage fistula.

Phase II Placebo-Controlled Study of the Effect and Safety of Nanvuranlat in Patients with Advanced Biliary Tract Cancers Previously Treated by Systemic Chemotherapy.

PURPOSE: To evaluate the efficacy and safety of nanvuranlat (a LAT1 inhibitor) monotherapy as a later-line treatment in advanced, metastatic, and refractory BTCs. PATIENTS AND METHODS: The multicenter, randomized, double-blind, placebo-controlled, phase II study was conducted across 14 leading Japanese cancer centers and hospitals. Nanvuranlat 25 mg/m2/day or placebo was given intravenously in cycles of five consecutive days, followed by nine days off. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and disease control rate (DCR). Subgroup analysis was performed in patients with high LAT1 expression and BTC-subtypes. RESULTS: A total of 211 patients were screened, 105 eligible patients were randomized, and then 70 received nanvuranlat and 35 received placebo. Nanvuranlat demonstrated an improvement in PFS when compared to placebo (Hazard Ratio (HR) 0.56; 95% CI, 0.34 - 0.90; P = 0.02). Grade 3 or higher adverse events were reported in 30.0% and 22.9% of those in the nanvuranlat and placebo groups, respectively. The overall survival (OS) was not statistically different between nanvuranlat- and placebo-treated patients. An exploratory analysis indicated that nanvuranlat is warranted to evaluate its long-term clinical benefit in patients with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer. CONCLUSION: Compared with placebo, nanvuranlat improved PFS in patients with advanced and refractory BTC with an acceptable safety profile. Further studies of this promising compound are warranted in the population of patients who are exhausted from treatment options.

Safety and efficacy of endoscopic ultrasound-guided pancreatic duct drainage using a drill dilator: a retrospective study from Japan.

Background/Aims: Dilation of the tract before stent deployment is a challenging step in endoscopic ultrasound-guided pancreatic duct drainage (EUS-PDD). In this study, we examined the effectiveness and safety of a novel spiral dilator, Tornus ES (Asahi Intec), for EUS-PDD. Methods: This was a retrospective, single-arm, observational study at Aichi Cancer Center Hospital. The punctured tract was dilated using a Tornus ES dilator in all EUS-PDD cases. Our primary endpoint was the technical success rate of initial tract dilation. Technical success was defined as successful fistula dilation using Tornus ES followed by successful stent insertion. Secondary endpoints were procedure times and early adverse events. Results: A total of 12 patients were included between December 2021 and March 2023. EUS-PDD was performed in 11 patients for post-pancreaticoduodenectomy anastomotic strictures and one patient with pancreatitis with duodenal perforation. The technical success rates of stent insertion and fistula dilation using Tornus ES dilator was 100%. The median procedure time was 24 minutes. No remarkable adverse events related to the procedure were observed, apart from fever, which occurred in 2 patients. Conclusions: Tract dilation in EUS-PDD using Tornus ES is effective and safe.

TOKYO criteria 2024 for the assessment of clinical outcomes of endoscopic biliary drainage.

The consensus-based TOKYO criteria were proposed as a standardized reporting system for endoscopic transpapillary biliary drainage. The primary objective was to address issues arising from the inconsistent reporting of stent outcomes across studies, which has complicated the comparability and interpretation of study results. However, the original TOKYO criteria were not readily applicable to recent modalities of endoscopic biliary drainage such as biliary drainage based on endoscopic ultrasound or device-assisted endoscopy. There are increasing opportunities for managing hilar biliary obstruction and benign biliary strictures through endoscopic drainage. Biliary ablation has been introduced to manage benign and malignant biliary strictures. In addition, the prolonged survival times of cancer patients have increased the importance of evaluating overall outcomes during the period requiring endoscopic biliary drainage rather than solely focusing on the patency of the initial stent. Recognizing these unmet needs, a committee has been established within the Japan Gastroenterological Endoscopy Society to revise the TOKYO criteria for current clinical practice. The revised criteria propose not only common reporting items for endoscopic biliary drainage overall, but also items specific to various conditions and interventions. The term "stent-demanding time" has been defined to encompass the entire duration of endoscopic biliary drainage, during which the overall stent-related outcomes are evaluated. The revised TOKYO criteria 2024 are expected to facilitate the design and reporting of clinical studies, providing a goal-oriented approach to the evaluation of endoscopic biliary drainage.

Internet of things-based approach for glycemic control in people with type 2 diabetes: A randomized controlled trial.

AIMS: The utilization of long-term effect of internet of things (IoT) on glycemic control is controversial. This trial aimed to examine the effect of an IoT-based approach for type 2 diabetes. MATERIALS AND METHODS: This randomized controlled trial enrolled 1,159 adults aged 20-74 years with type 2 diabetes with a HbA1c of 6.0-8.9% (42-74 mmol/mol), who were using a smartphone on a daily basis were randomly assigned to either the IoT-based approach group (ITG) or the control group (CTG). The ITG were supervised to utilize an IoT automated system that demonstrates a summary of lifelogging data (weight, blood pressure, and physical activities) and provides feedback messages that promote behavioral changes in both diet and exercise. The primary end point was a HbA1c change over 52 weeks. RESULTS: Among the patients, 581 were assigned to the ITG and 578 were in the CTG. The changes in HbA1c from baseline to the final measurement at 52 weeks [mean (standard deviation)] were -0.000 (0.6225)% in ITG and - 0.006 (0.6449)% in CTG, respectively (P = 0.8766). In the per protocol set, including ITG using the IoT system almost daily and CTG, excluding those using the application almost daily, the difference in HbA1c from baseline to 52 weeks were -0.098 (0.579)% and 0.027 (0.571)%, respectively (P = 0.0201). We observed no significant difference in the adverse event profile between the groups. CONCLUSIONS: The IoT-based approach did not reduce HbA1c in patients with type 2 diabetes. IoT-based intervention using data on the daily glycemic control and HbA1c level may be required to improve glycemic control.

A case of acinar cell carcinoma originating from the accessory papilla of the duodenum.

CASE PRESENTATION: A 61-year-old female was referred to our hospital with a neoplastic lesion in the duodenum. Computed tomography with contrast enhancement revealed a 10-mm tumor in the duodenum. Upper gastrointestinal endoscopy revealed a submucosal tumor-like lesion in the descending part of the duodenum. Endoscopic ultrasound revealed a well-defined hypoechoic tumor. Biopsy and immunohistochemical findings including negative Synaptophysin and Chromogranin A staining and positive Trypsin and BCL10 staining suggested a carcinoma with acinar cell differentiation. Pancreatoduodenectomy was performed, and the resected specimen had a 15-mm solid nodule in the submucosal layer of the duodenum. Pancreatogram of the resected specimen revealed a tumor localized in the accessory papilla region. In histopathological examination, the tumor was found in the submucosa of the duodenum with pancreatic tissue present nearby, and these were separated from the pancreatic parenchyma by the duodenal muscle layer. These findings led to a diagnosis of acinar cell carcinoma originating from the accessory papilla of the duodenum. CONCLUSION: Acinar cell carcinoma originating from the accessory papilla of the duodenum is exceptionally rare, with no reported cases to date. The origin was considered to be pancreatic tissue located in the accessory papilla region.

Safety and efficacy of novel oblique-viewing scope for B2-endoscopic ultrasound-guided hepaticogastrostomy.

BACKGROUND/AIMS: Endoscopic ultrasound (EUS)-guided hepaticogastrostomy (EUS-HGS) performed at the intrahepatic bile duct segment 3 (B3) is widely used for biliary drainage. Although performing post-puncture procedures is easier in the intrahepatic bile duct segment 2 (B2) when using a conventional oblique-viewing (OV) EUS scope, this method may cause transesophageal puncture and severe adverse events. We evaluated the safety and efficacy of B2 puncture using a novel OV-EUS scope. METHODS: In this single-center retrospective study, we prospectively enrolled and collected data from 45 patients who consecutively underwent EUS-HGS procedures with a novel OV-EUS scope between September 2021 and December 2022 at our cancer center. RESULTS: The technical success rates of B2-EUS-HGS and EUS-HGS were 93.3% (42/45) and 97.8% (44/45), respectively. The early adverse event rate was 8.9% (4/45) with no cases of scope changes or transesophageal punctures. The median procedure time was 13 minutes (range, 5-30). CONCLUSIONS: B2-EUS-HGS can be performed safely with the novel EG-740UT (Fujifilm) OV-scope without transesophageal puncture and with a high success rate. B2-EUS-HGS using this novel OV scope may be the preferred strategy for EUS-HGS.

Consensus statements on endoscopic ultrasound-guided tissue acquisition. Guidelines from the Asian Endoscopic Ultrasound Group.

OBJECTIVES: This consensus was developed by the Asian EUS Group (AEG), who aimed to formulate a set of practice guidelines addressing various aspects of endoscopic ultrasound-guided tissue acquisition (EUS-TA). METHODS: The AEG initiated the development of consensus statements and formed an expert panel comprising surgeons, gastroenterologists, and pathologists. Three online consensus meetings were conducted to consolidate the statements and votes. The statements were presented and discussed in the first two consensus meetings and revised according to comments. Final voting was conducted at a third consensus meeting. The Grading of Recommendations, Assessment, Development, and Evaluation system was adopted to define the strength of the recommendations and quality of evidence. RESULTS: A total of 20 clinical questions and statements regarding EUS-TA were formulated. The committee recommended that fine-needle biopsy (FNB) needles be preferred over conventional fine-needle aspiration (FNA) needles for EUS-TA of subepithelial lesions. For solid pancreatic masses, rapid on-site evaluation is not routinely recommended when FNB needles are used. For dedicated FNB needles, fork-tip and Franseen-tip needles have essentially equivalent performance. CONCLUSION: This consensus provides guidance for EUS-TA, thereby enhancing the quality of EUS-TA.

Trends of HbA1c and BMI in People with Type 2 Diabetes: A Japanese Claims-Based Study.

INTRODUCTION: Obesity prevalence has increased in Japan in recent years. Given the strong association of obesity with poor glycemic control, and increased risk of type 2 diabetes (T2D) with central obesity, this study describes the current trends and relationships between glycated hemoglobin (HbA1c), body mass index (BMI), and waist circumference in the Japanese people with T2D. METHODS: This was a retrospective, cross-sectional study of people with T2D who had at least one recorded HbA1c and BMI (or waist circumference) value in the Japan Medical Data Center Claims database. Five annual cohorts of the study population were formed between January 2017 and December 2021. Annual trends of HbA1c across BMI categories (obesity class I [≥ 25 ~ < 30 kg/m2]-IV [≥ 40 kg/m2]) and in people with central obesity (waist circumference: ≥ 85 cm in men; ≥ 90 cm in women) were described by sex and age groups. RESULTS: Overall, 106,089 people with T2D (HbA1c and BMI data: 106,079; HbA1c and waist circumference data: 105,424) were included, with the majority of people belonging to obesity class I (range: 39.7-40.6%) and obesity class II (range: 16.2-17.7%) categories across all annual cohorts. People in higher BMI categories had higher mean HbA1c, with > 50% of people with T2D in obesity class I-IV (54.8-56.5%) having HbA1c ≥ 7%. Between 2017 and 2021, BMI and waist circumference increased in the age group 18-44 years. More than 50% of people with T2D and central obesity in both sexes and people of age group 18-44 years across obesity class I-IV or with central obesity had HbA1c ≥ 7%. CONCLUSION: More than half of the people with T2D belonging to obesity class I-IV or central obesity had poor glycemic control (HbA1c ≥ 7%), especially in the 18-44 age group. This highlights the need for body weight management for better glycemic control in relatively young Japanese people with T2D and obesity.

The New potential for Using Franseen Needles in Interventional EUS.

Objective Adverse events such as bile leakage and bleeding are among the issues that need to be resolved in EUS-guided choledochoduodenostomy (EUS-CDS). To overcome this problem, we developed a new EUS-CDS technique using a 19-G Franseen needle without tract dilation. This study aimed to evaluate the safety and efficacy of the new EUS-CDS technique. Methods This single-center retrospective study included 20 consecutive patients who underwent EUS-CDS for primary drainage using a 19-G Franseen needle between March 2020 and May 2023. The primary endpoint was the technical success rate of EUS-CDS without tract dilation. Results The technical success rate of EUS-CDS was 20/20 (100%). None of the patients required any additional tract dilation, such as by using a balloon or electric cautery. The median procedure time was 7.8 (range, 3.2-19.4) min. No early adverse events were observed. Conclusion The 19-G Franseen needle appeared to have a sufficient dilatory effect during puncturing. This EUS-CDS technique appears to be safe and effective and has the advantages of no adverse events and it is also a simplified procedure, which suggests its potential for widespread use in primary drainage.

Forward viewing liner echoendoscopy for therapeutic interventions.

Therapeutic endoscopic ultrasonography (EUS) procedures using the forward-viewing convex EUS (FV-EUS) have been reviewed based on the articles reported to date. The earliest reported procedure is the drainage of pancreatic pseudocysts using FV-EUS. However, the study on drainage of pancreatic pseudocysts focused on showing that drainage is possible with FV-EUS rather than leveraging its features. Subsequently, studies describing the characteristics of FV-EUS have been reported. By using FV-EUS in EUS-guided choledochoduodenostomy, double punctures in the gastrointestinal tract can be avoided. In postoperative modified anatomical cases, using the endoscopic function of FV-EUS, procedures such as bile duct drainage from anastomosis, pancreatic duct drainage from the afferent limb, and abscess drainage from the digestive tract have been reported. When a perpendicular puncture to the gastrointestinal tract is required or when there is a need to insert the endoscope deep into the gastrointestinal tract, FV-EUS is considered among the options.

Interaction between type 2 diabetes polygenic risk and physical activity on cardiovascular outcomes.

AIMS: The beneficial effects of exercise on reducing the risk of cardiovascular disease are established. However, the potential interaction between genetic risk for type 2 diabetes and physical activity on cardiovascular outcomes remains elusive. We aimed to investigate the effect of type 2 diabetes genetic risk-physical activity interaction on cardiovascular outcomes in individuals with diabetes. METHODS AND RESULTS: Using the UK Biobank cohort, we investigated the effect of type 2 diabetes genetic risk-physical activity interaction on three-point and four-point major adverse cardiovascular events (MACE), in 25 701 diabetic participants. We used a polygenic risk score for type 2 diabetes (PRS_T2D) as a measure of genetic risk for type 2 diabetes. We observed a significant interaction between PRS_T2D and physical activity on cardiovascular outcomes (three-point MACE: P trend for interaction = 0.0081; four-point MACE: P trend for interaction = 0.0037). Among participants whose PRS_T2D was in the first or second quartile, but not in the third or fourth quartile, each 10 metabolic equivalents (METs) hours per week of physical activity decreased the risk of three-point or four-point MACE. Furthermore, restricted cubic spline analysis indicated that intense physical activity (>80 METs hours per week, which was self-reported by 12.7% of participants) increased the risk of cardiovascular outcomes among participants whose PRS_T2D was in the fourth quartile. Sub-group analysis suggested that negative impact of intense physical activity was observed only in non-insulin users. CONCLUSION: The beneficial effect of physical activity on cardiovascular outcomes disappeared among those with high genetic risk for type 2 diabetes.

The beneficial effects of exercise on reducing the risk of cardiovascular disease are established. However, whether genetic risk for type 2 diabetes influences the effect of physical activity on cardiovascular outcomes in individuals with diabetes remains elusive. We aimed to investigate interaction between genetic risk for type 2 diabetes and physical activity on major adverse cardiovascular events (MACE) in individuals with diabetes.The beneficial effect of physical activity on cardiovascular outcomes disappeared among diabetic individuals with high genetic risk for type 2 diabetes, due to significant gene­environment interaction; in this subpopulation, intense physical activity was associated with increased risk of cardiovascular outcomes.Personalized exercise recommendations tailored to avoid excessively intense exercise, in combination with genetic screening of high-risk individuals, would be required.

Clinical utility of endoscopic ultrasound-guided tissue acquisition for comprehensive genomic profiling of patients with biliary tract cancer, especially with intrahepatic cholangiocarcinoma.

BACKGROUND/AIMS: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is a standard diagnostic method for biliary tract cancer (BTC), and samples obtained in this manner may be used for comprehensive genomic profiling (CGP). This study evaluated the utility of EUS-TA for CGP in a clinical setting and determined the factors associated with the adequacy of CGP in patients with BTC. METHODS: CGP was attempted for 105 samples from 94 patients with BTC at the Aichi Cancer Center, Japan, from October 2019 to April 2022. RESULTS: Overall, 77.1% (81/105) of the samples were adequate for CGP. For 22-G or 19-G fine-needle biopsy (FNB), the sample adequacy was 85.7% (36/42), which was similar to that of surgical specimens (94%, p=0.45). Univariate analysis revealed that 22-G or larger FNB needle usage (86%, p=0.003), the target primary lesions (88%, p=0.015), a target size ≥30 mm (100%, p=0.0013), and number of punctures (90%, p=0.016) were significantly positively associated with CGP sample adequacy. CONCLUSIONS: EUS-TA is useful for CGP tissue sampling in patients with BTC. In particular, the use of 22-G or larger FNB needles may allow for specimen adequacy comparable to that of surgical specimens.

Endoscopic ultrasound-guided tissue acquisition for comprehensive genomic profiling.

Advances in next-generation sequencing have made comprehensive genomic profiling (CGP) using tumor tissue specimens and liquid biopsy using blood samples feasible in routine clinical practice. In the context of pancreaticobiliary cancer, it is necessary to consider CGP in formulating individualized treatment strategies. Performing CGP with tumor tissue specimens requires a sufficient number of high-quality samples. EUS-guided tissue acquisition (EUS-TA) is expected to play a significant role in this regard, and endosonographers need to address this role. Here, we review the current status of EUS-TA for CGP focusing on pancreatic cancer and biliary tract cancer.

Safety of endoscopic ultrasound-guided hepaticogastrostomy in patients with malignant biliary obstruction and ascites.

BACKGROUND/AIMS: Endoscopic ultrasound (EUS)-guided hepaticogastrostomy (EUS-HGS) is useful for patients with biliary cannulation failure or inaccessible papillae. However, it can lead to serious complications such as bile peritonitis in patients with ascites; therefore, development of a safe method to perform EUS-HGS is important. Herein, we evaluated the safety of EUS-HGS with continuous ascitic fluid drainage in patients with ascites. METHODS: Patients with moderate or severe ascites who underwent continuous ascites drainage, which was initiated before EUS-HGS and terminated after the procedure at our institution between April 2015 and December 2022, were included in the study. We evaluated the technical and clinical success rates, EUS-HGS-related complications, and feasibility of re-intervention. RESULTS: Ten patients underwent continuous ascites drainage, which was initiated before EUS-HGS and terminated after completion of the procedure. Median duration of ascites drainage before and after EUS-HGS was 2 and 4 days, respectively. Technical success with EUS-HGS was achieved in all 10 patients (100%). Clinical success with EUS-HGS was achieved in 9 of the 10 patients (90 %). No endoscopic complications such as bile peritonitis were observed. CONCLUSION: In patients with ascites, continuous ascites drainage, which is initiated before EUS-HGS and terminated after completion of the procedure, may prevent complications and allow safe performance of EUS-HGS.

Is preoperative pancreatic juice cytology useful for determining therapeutic strategies for patients with intraductal papillary mucinous neoplasm of the pancreas?

BACKGROUND: We compared the results of preoperative pancreatic juice cytology (PJC) and final pathological diagnosis after resection in patients who underwent resection of intraductal papillary mucinous neoplasm (IPMN) of the pancreas to determine whether preoperative PJC can help determine therapeutic strategies. METHODS: Of 1130 patients who underwent surgical resection IPMN at 11 Japanese tertiary institutions, the study included 852 patients who underwent preoperative PJC guided by endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: The accuracy of preoperative PJC for differentiation between cancerous and noncancerous lesions were 55% for IPMN overall; 59% for the branch duct type; 49% for the main pancreatic duct type; 53% for the mixed type, respectively. On classifying IPMN according to the diameters of the mural nodule (MN) and main pancreatic duct (MPD), the corresponding values for diagnostic performance were 40% for type 1 (MN ≥5 mm and MPD ≥ 10 mm); 46% for type 2 (MN ≥5 mm and MPD < 10 mm); 61% for type 3 (MN < 5 mm and MPD ≥ 10 mm); 72% for type 4 (MN < 5 mm and MPD < 10 mm), respectively. CONCLUSIONS: PJC in IPMN is not a recommended examination because of its low overall sensitivity and no significant difference in diagnostic performance by type, location, or subclassification. Although the sensitivity is low, the positive predictive value is high, so we suggest that pancreatic juice cytology be performed only in cases where the patient is not sure about surgery.