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.

Evidence-based clinical practice guidelines for cholelithiasis 2021.

The Japanese Society of Gastroenterology first published evidence-based clinical practice guidelines for cholelithiasis in 2010, followed by a revision in 2016. Currently, the revised third edition was published to reflect recent evidence on the diagnosis, treatment, and prognosis of cholelithiasis conforming to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Following this revision, the present English version of the guidelines was updated and published herein. The clinical questions (CQ) in the previous version were reviewed and rearranged into three newly divided categories: background questions (BQ) dealing with basic background knowledge, CQ, and future research questions (FRQ), which refer to issues that require further accumulation of evidence. Finally, 52 questions (29 BQs, 19 CQs, and 4 FRQs) were adopted to cover the epidemiology, pathogenesis, diagnosis, treatment, complications, and prognosis. Based on a literature search using MEDLINE, Cochrane Library, and Igaku Chuo Zasshi databases for the period between 1983 and August 2019, along with a manual search of new information reported over the past 5 years, the level of evidence was evaluated for each CQ. The strengths of recommendations were determined using the Delphi method by the committee members considering the body of evidence, including benefits and harms, patient preference, and cost-benefit balance. A comprehensive flowchart was prepared for the diagnosis and treatment of gallbladder stones, common bile duct stones, and intrahepatic stones, respectively. The current revised guidelines are expected to be of great assistance to gastroenterologists and general physicians in making decisions on contemporary clinical management for cholelithiasis patients.

Noninvasive Evaluation of GIP Effects on ß-Cell Mass Under High-Fat Diet.

Pancreatic ß-cell mass (BCM) has an importance in the pathophysiology of diabetes mellitus. Recently, glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging has emerged as a promising tool for BCM evaluation. While glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide (GIP) is known to be involved in high-fat diet (HFD)-induced obesity, the effect of GIP on BCM is still controversial. In this study, we investigated indium 111 (111In)-labeled exendin-4 derivative ([Lys12(111In-BnDTPA-Ahx)]exendin-4) single-photon emission computed tomography/computed tomography (SPECT/CT) as a tool for evaluation of longitudinal BCM changes in HFD-induced obese mice, at the same time we also investigated the effects of GIP on BCM in response to HFD using GIP-knockout (GIP-/-) mice. 111In-exendin-4 SPECT/CT was able to distinguish control-fat diet (CFD)-fed mice from HFD-fed mice and the pancreatic uptake values replicated the BCM measured by conventional histological methods. Furthermore, BCM expansions in HFD-fed mice were demonstrated by time-course changes of the pancreatic uptake values. Additionally, 111In-exendin-4 SPECT/CT demonstrated the distinct changes in BCM between HFD-fed GIP-/- (GIP-/-+HFD) and wild-type (WT+HFD) mice; the pancreatic uptake values of GIP-/-+HFD mice became significantly lower than those of WT+HFD mice. The different changes in the pancreatic uptake values between the two groups preceded those in fat accumulation and insulin resistance. Taken together with the finding of increased ß-cell apoptosis in GIP-/-+HFD mice compared with WT+HFD mice, these data indicated that GIP has preferable effects on BCM under HFD. Therefore, 111In-exendin-4 SPECT/CT can be useful for evaluating increasing BCM and the role of GIP in BCM changes under HFD conditions.

Clinical practice guidelines for endoscopic papillectomy.

The Japan Gastroenterological Endoscopy Society has developed the "Clinical Practice Guidelines for Endoscopic Papillectomy (EP)" as a fundamental guideline using scientific approach. EP is a recently spreading therapeutic modality for ampullary tumors ranked as high risk endoscopic technique. Because of the paucity of high level of evidence, strength of recommendations had to be determined by a consensus among specialists. These guidelines, shed light on the following five issues: Indications, Preoperative/intraoperative preparations and techniques, Early adverse events, Therapeutic outcomes and remnants/recurrences, and Follow-up and late adverse events, to guide current clinical practice on EP.

First-in-Human Evaluation of Positron Emission Tomography/Computed Tomography With [18F]FB(ePEG12)12-Exendin-4: A Phase 1 Clinical Study Targeting GLP-1 Receptor Expression Cells in Pancreas.

Pancreatic ß-cell mass (BCM) has a central importance in the pathophysiology of diabetes mellitus. Recently, pancreatic ß-cell-specific imaging, especially positron emission tomography (PET) with exendin-based probes, has emerged for non-invasive evaluation of BCM. We developed a novel exendin-based probe labeled with fluorine-18, [18F]FB(ePEG12)12-exendin-4 (18F-Ex4) for PET imaging. We subsequently conducted a first-in-human phase 1 study of 18F-Ex4 PET/computed tomography (CT) and investigated the safety and utility for visualizing the pancreas. Six healthy male subjects were enrolled in this study. A low dose (37.0 MBq) of 18F-Ex4 PET/CT was administered (first cohort: n = 2), and subsequently a higher dose (74.0 MBq) was administered (second cohort: n = 4). In the first and second cohorts, 38.6 ± 4.8 and 71.1 ± 4.8 MBq of 18F-Ex4 were administered, respectively. No serious adverse events were observed in both groups. Only one participant in the first cohort showed transient hypoglycemia during the PET scans. 18F-Ex4 PET/CT successfully visualized the pancreas in all participants. The mean standardized uptake value of the pancreas was found to be higher than that in the surrounding organs, except for the bladder and kidney, during the observation. Dosimetry analyses revealed the effective systemic doses of 18F-Ex4 as 0.0164 ± 0.0019 mSv/MBq (first cohort) and 0.0173 ± 0.0020 mSv/MBq (second cohort). 18F-Ex4 PET/CT demonstrated the safety and utility for non-invasive visualization of the pancreas in healthy male subjects. 18F-Ex4 is promising for clinical PET imaging targeting pancreatic ß cells.

Distinctive detection of insulinoma using [18F]FB(ePEG12)12-exendin-4 PET/CT.

Specifying the exact localization of insulinoma remains challenging due to the lack of insulinoma-specific imaging methods. Recently, glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging, especially positron emission tomography (PET), has emerged. Although various radiolabeled GLP-1R agonist exendin-4-based probes with chemical modifications for PET imaging have been investigated, an optimal candidate probe and its scanning protocol remain a necessity. Thus, we investigated the utility of a novel exendin-4-based probe conjugated with polyethylene glycol (PEG) for [18F]FB(ePEG12)12-exendin-4 PET imaging for insulinoma detection. We utilized [18F]FB(ePEG12)12-exendin-4 PET/CT to visualize mouse tumor models, which were generated using rat insulinoma cell xenografts. The probe demonstrated high uptake value on the tumor as 37.1 ± 0.4%ID/g, with rapid kidney clearance. Additionally, we used Pdx1-Cre;Trp53R172H;Rbf/f mice, which developed endogenous insulinoma and glucagonoma, since they enabled differential imaging evaluation of our probe in functional pancreatic neuroendocrine neoplasms. In this model, our [18F]FB(ePEG12)12-exendin-4 PET/CT yielded favorable sensitivity and specificity for insulinoma detection. Sensitivity: 30-min post-injection 66.7%, 60-min post-injection 83.3%, combined 100% and specificity: 30-min post-injection 100%, 60-min post-injection 100%, combined 100%, which was corroborated by the results of in vitro time-based analysis of internalized probe accumulation. Accordingly, [18F]FB(ePEG12)12-exendin-4 is a promising PET imaging probe for visualizing insulinoma.

Clinical Questions and Answers on Gastrointestinal Endoscopy during the Novel Coronavirus Disease 2019 pandemic.

Some situations may require endoscopy during the COVID-19 (Coronavirus Disease 2019) pandemic. Here, we describe the necessary precautions in the form of clinical questions and answers (Q&A) regarding the safe deployment of gastrointestinal endoscopy in such situations while protecting endoscopy staff and patients from infection. Non-urgent endoscopy should be postponed. The risk of infection in patients should be evaluated in advance by questionnaire and body temperature. The health of staff must be checked every day. Decisions to employ endoscopy should be based on the institutional conditions and aims of endoscopy. All endoscopic staff need to wear appropriate personal protective equipment (PPE). The endoscope and other devices should be cleaned and disinfected after procedures in accordance with the relevant guidelines. Optimal management of the endoscopy unit is required. Endoscopy for infected patients or those with suspected infection demands exceptional caution. When a patient who undergoes endoscopy is later found to have COVID-19, the members of staff involved are considered exposed to the virus and must not work for at least 14 days if their PPE is considered insufficient. When PPE resources are limited, some equipment may be used continuously throughout a shift as long as it is not contaminated. Details of the aforementioned protective measures are described.

Association of glucagon-like peptide-1 receptor-targeted imaging probe with in vivo glucagon-like peptide-1 receptor agonist glucose-lowering effects.

AIMS/INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RA) are used for treatment of type 2 diabetes mellitus worldwide. However, some patients do not respond well to the therapy, and caution must be taken for certain patients, including those with reduced insulin secretory capacity. Thus, it is clinically important to predict the efficacy of GLP-1RA therapy. GLP-1R-targeted imaging has recently emerged to visualize and quantify ß-cells. We investigated whether GLP-1R-targeted imaging can predict the efficacy of GLP-1RA treatment. MATERIALS AND METHODS: We developed 111 Indium-labeled exendin-4 derivative (111 In-Ex4) as a GLP-1R-targeting probe. Diabetic mice were selected from NONcNZO10/LtJ male mice that were fed for different durations with 11% fat chow. After 3-week administration of dulaglutide as GLP-1RA therapy, mice with non-fasting blood glucose levels <300 mg/dL and >300 mg/dL were defined as responders and non-responders, respectively. In addition, ex vivo 111 In-Ex4 pancreatic accumulations (111 In-Ex4 pancreatic values) were examined. RESULTS: The non-fasting blood glucose levels after treatment were 172.5 ± 42.4 mg/dL in responders (n = 4) and 330.8 ± 20.7 mg/dL in non-responders (n = 5), respectively. Ex vivo 111 In-Ex4 pancreatic values showed significant correlations with post-treatment glycohemoglobin and glucose area under curve during an oral glucose tolerance test (R2  = 0.76 and 0.80; P < 0.01 and <0.01, respectively). The receiver operating characteristic area under curve for identifying responders by ex vivo 111 In-Ex4 pancreatic values was 1.00 (P < 0.01). CONCLUSION: Ex vivo 111 In-Ex4 pancreatic values reflected dulaglutide efficacy, suggesting clinical possibilities for expanding GLP-1R-targeted imaging applications.

Gastrointestinal endoscopy in the era of the acute pandemic of coronavirus disease 2019: Recommendations by Japan Gastroenterological Endoscopy Society (Issued on April 9th, 2020).

All gastrointestinal endoscopic procedures have a high risk of aerosol contamination of the coronavirus disease 2019 (COVID-19) to endoscopists, nurses, and healthcare assistants. Given the current pandemic situation of COVID-19, the Japan Gastroenterological Endoscopy Society issued the recommendation for gastrointestinal (GI) endoscopy based on the status of COVID-19 as of April 9, 2020, in Japan: (i) indications for GI endoscopy in the pandemic of COVID-19; (ii) practical protective equipment for medical personnel depending on the risk for COVID-19; (iii) preprocedural management, such as pharyngeal local anesthesia using lidocaine spray which has a potential to generate the aerosols; (iv) ideal settings of the endoscopy room including the numbers of the staff and the patients; (v) postprocedural management, such as undressing and follow-up of the patients, as well as the involved staff, were documented to fit the practical scenarios in GI endoscopy, with the available data in Japan and the world. We believe that certain measures will prevent further spread of COVID-19.

Investigation of the preservation effect of canagliflozin on pancreatic beta cell mass using SPECT/CT imaging with 111In-labeled exendin-4.

Radiolabeled exendin derivatives are promising for non-invasive quantification of pancreatic beta cell mass (BCM); longitudinal observation of BCM for evaluation of therapeutic effects has not been achieved. The aim of this study is to demonstrate the usefulness of our developing method using [Lys12(111In-BnDTPA-Ahx)]exendin-4 to detect longitudinal changes in BCM. We performed a longitudinal study with obese type 2 diabetes model (db/db) mice administered canagliflozin, which is reported to preserve BCM. Six-week-old mice were assigned to a canagliflozin-administered group or a control group. Blood glucose levels of the canagliflozin group were significantly lower than those of the control group. Plasma insulin levels, insulin secretion during OGTT and insulin content in the pancreas were preserved in the canagliflozin group in comparison with those in the control group. According to SPECT/CT imaging analysis using [Lys12(111In-BnDTPA-Ahx)]exendin-4, pancreatic uptake was significantly decreased in the control group, whereas there was no significant change in the canagliflozin group. After nine weeks, both pancreatic uptake and BCM of the canagliflozin group were significantly higher than those of the control group, and a correlation between them was observed. In conclusion, our imaging method confirmed the BCM-preservation effect of canagliflozin, and demonstrated its potential for longitudinal evaluation of BCM.

Noninvasive Evaluation of GPR119 Agonist Effects on ß-Cell Mass in Diabetic Male Mice Using 111In-Exendin-4 SPECT/CT.

Longitudinal observation of pancreatic ß-cell mass (BCM) remains challenging because noninvasive techniques for determining BCM in vivo have not been established. Such observations would be useful for the monitoring of type 2 diabetes mellitus, a progressive disease involving loss of pancreatic BCM and function. An indium 111 (111In)-labeled exendin-4 derivative ([Lys12(111In-BnDTPA-Ahx)]exendin-4) targeting the glucagon-like peptide-1 receptor has been developed recently as a promising probe for quantifying the BCM noninvasively. In the present study, we used the 111In-exendin-4 single-photon emission CT/CT (SPECT/CT) technique to investigate the efficacy of DS-8500a, a novel G protein-coupled receptor-119 agonist currently under investigation for type 2 diabetes mellitus treatment in prediabetic db/db mice under dietary restriction. During the 8-week study, the treatment of mice with DS-8500a delayed and attenuated the progression of glucose intolerance compared with mice under dietary restriction alone. 111In-exendin-4 SPECT/CT of db/db mice revealed continuously decreasing radioactive isotope (RI) intensity in the pancreas during the 8-week intervention. DS-8500a attenuated this decrease and preserved pancreatic RI accumulation compared with dietary restriction alone at the end of the observation period. This result was corroborated not only by ex vivo pancreatic analysis using the [Lys12(111In-BnDTPA-Ahx)]exendin-4 probe but also by conventional histological BCM analysis. These results indicate that DS-8500a attenuates the progression of BCM loss beyond that of dietary restriction alone in prediabetic db/db mice. These results have shown that 111In-exendin-4 SPECT/CT will be useful for noninvasive longitudinal investigation of BCM in vivo.

Noninvasive longitudinal quantification of ß-cell mass with [111In]-labeled exendin-4.

Currently, quantifying ß-cell mass (BCM) requires harvesting the pancreas. In this study, we investigated a potential noninvasive method to quantify BCM changes longitudinally using [Lys12(111In-BnDTPA-Ahx)]exendin-4 ([111In]-Ex4) and single-photon emission computed tomography (SPECT). We used autoradiography and transgenic mice expressing green fluorescent protein under the control of mouse insulin 1 gene promotor to evaluate the specificity of [111In]-Ex4 toward ß cells. Using nonobese diabetic (NOD) mice, we injected [111In]-Ex4 (3.0 MBq) intravenously and performed SPECT 30 min later, repeating this at a 2-wk interval. After the second scan, we harvested the pancreas and calculated BCM from immunohistochemically stained pancreatic sections. Specific accumulation of [111In]-Ex4 in ß cells was confirmed by autoradiography, with a significant correlation (r = 0.94) between the fluorescent and radioactive signal intensities. The radioactive signal from the pancreas in the second SPECT scan significantly correlated (r = 0.89) with BCM calculated from the immunostained pancreatic sections. We developed a regression formula to estimate BCM from the radioactive signals from the pancreas in SPECT scans. BCM can be quantified longitudinally and noninvasively by SPECT imaging with [111In]-Ex4. This technique successfully demonstrated longitudinal changes in BCM in NOD mice before and after onset of hyperglycemia.-Fujita, N., Fujimoto, H., Hamamatsu, K., Murakami, T., Kimura, H., Toyoda, K., Saji, H., Inagaki, N. Noninvasive longitudinal quantification of ß-cell mass with [111In]-labeled exendin-4.

Clinical practice guidelines for safe performance of endoscopic ultrasound/ultrasonography-guided biliary drainage: 2018.

Endoscopic ultrasound/ultrasonography-guided biliary drainage (EUS-BD) is a relatively new modality for biliary drainage after failed or difficult transpapillary biliary cannulation. Despite its clinical utility, EUS-BD can be complicated by severe adverse events such as bleeding, perforation, and peritonitis. The aim of this paper is to provide practice guidelines for safe performance of EUS-BD as well as safe introduction of the procedure to non-expert centers. The guidelines comprised patient-intervention-comparison-outcome-formatted clinical questions (CQs) and questions (Qs), which are background statements to facilitate understanding of the CQs. A literature search was performed using the PubMed and Cochrane Library databases. Statement, evidence level, and strength of recommendation were created according to the GRADE system. Four committees were organized: guideline creation, expert panelist, evaluation, and external evaluation committees. We developed 13 CQs (methods, device selection, supportive treatment, management of adverse events, education and ethics) and six Qs (definition, indication, outcomes and adverse events) with statements, evidence levels, and strengths of recommendation. The guidelines explain the technical aspects, management of adverse events, and ethics of EUS-BD and its introduction to non-expert institutions.

Establishment of a method for in-vivo SPECT/CT imaging analysis of 111In-labeled exendin-4 pancreatic uptake in mice without the need for nephrectomy or a secondary probe.

INTRODUCTION: Radiolabeled exendin derivatives have been developed to visualize and quantify pancreatic beta cells. However, there are currently no established methods for analyzing in-vivo SPECT/CT images to quantify probe accumulation in the pancreas in rodent models. In this study, we aimed to establish an analytical method for murine in-vivo SPECT/CT imaging. METHODS: First, we investigated the correlation between radioactivity measured by curiemeter and uptake calculated from SPECT/CT images of pancreata harvested after probe injection. Second, ROI volume necessary for reliable estimation of pancreatic uptake value was also examined. Third, the influence of high renal uptake on analysis was investigated with SPECT/CT imaging of harvested kidneys. Fourth, we compared pancreatic uptake values and ROI volumes estimated from in-vivo SPECT/CT images of pre- and post-nephrectomy mice. Finally, we assessed the correlation between the pancreatic uptake values from in-vivo SPECT/CT image analysis and radioactivity of harvested pancreata determined with a curiemeter. RESULTS: Radioactivity of harvested pancreata measured by curiemeter and uptake values derived from SPECT/CT imaging of harvested pancreas showed an almost perfect correlation (r = 0.99, p < 0.001). Analysis using ROIs with >40% of the volume of the whole pancreas enabled reliable estimates of uptake (%CV < 10%). Exclusion of the perirenal space 2.7 mm from the kidney surface removed the influence of high renal uptake. Setting the uptake value of post-nephrectomy pancreatic ROIs as 100%, the uptake estimated from pre-nephrectomy images was comparable (102.9 ±â€¯2.2%). A strong correlation was observed between pancreatic radioactivity measured by curiemeter and the uptake value derived from in-vivo SPECT/CT imaging (r = 0.90, p < 0.001). CONCLUSION: Our analytical method without nephrectomy or additional probes enables reliable quantification of the pancreatic uptake of 111In-labeled exendin-4 using in-vivo SPECT/CT imaging. The quantification of rodent BCM with our method would be helpful to drug development.

Japan Gastroenterological Endoscopy Society guidelines for endoscopic papillary large balloon dilation.

The Japan Gastroenterological Endoscopy Society has developed the 'EPLBD Clinical Practice Guidelines' as fundamental guidelines based on new scientific techniques. EPLBD is a treatment method that has recently become widely used for choledocolithiasis. The evidence level in this field is usually low, and in many instances, the recommendation grading has to be determined on the basis of expert consensus. At this point, the guidelines are divided into the following six sections according to the 'EST Clinical Practice Guidelines': (i) Indications, (ii) procedures, (iii) special cases, (iv) procedure-related adverse events, (v) treatment outcomes, and (vi) postoperative follow up observation.

Real-life glycemic control in patients with type 2 diabetes treated with insulin therapy: A prospective, longitudinal cohort study (Diabetes Distress and Care Registry at Tenri [DDCRT 9]).

AIMS/INTRODUCTION: We investigated the association between four insulin regimens, and increase in glycated hemoglobin (HbA1c) and insulin dose in a real-life clinical setting because there are no data about them among insulin regimens. MATERIALS AND METHODS: Participants included 757 patients with type 2 diabetes having been treated with insulin therapy for more than 1 year. The four insulin regimens were regimen 1 (long-acting insulin, once daily), regimen 2 (biphasic insulin, twice daily), regimen 3 (biphasic insulin, three times daily) and regimen 4 (basal-bolus therapy). Main outcomes were increases in HbA1c levels >0.5% and increases in daily insulin units after 1 year. We carried out multivariable analyses to examine differences in glycemic control and insulin dose with adjustment for possible confounders. RESULTS: Mean HbA1c level and duration of insulin therapy were 7.8% and 11.3 years, respectively. HbA1c levels increased by >0.5% at follow up in 22.8, 24.9, 20.7, and 29.3% of participants using regimen 1, 2, 3 and 4, respectively, with no significant differences between groups. Daily insulin doses increased in 62.3, 68.8, 65.3 and 38.6% of patients, respectively (P < 0.001). Multivariable regression analysis showed that patients who received regimen 4 had significantly lower odds of requiring future insulin dose increases than those who had received regimen 2 (adjusted odds ratio 0.24, 95% confidence interval 0.14-0.41; P < 0.001). CONCLUSIONS: Many patients receiving insulin therapy showed increases in HbA1c levels and insulin doses 1 year later. The smallest increase in insulin dose was observed in the basal-bolus therapy group compared with other regimens.

Evaluation of 18F-labeled exendin(9-39) derivatives targeting glucagon-like peptide-1 receptor for pancreatic ß-cell imaging.

ß-cell mass (BCM) is known to be decreased in subjects with type-2 diabetes (T2D). Quantitative analysis for BCM would be useful for understanding how T2D progresses and how BCM affects treatment efficacy and for earlier diagnosis of T2D and development of new therapeutic strategies. However, a noninvasive method to measure BCM has not yet been developed. We developed four 18F-labeled exendin(9-39) derivatives for ß-cell imaging by PET: [18F]FB9-Ex(9-39), [18F]FB12-Ex(9-39), [18F]FB27-Ex(9-39), and [18F]FB40-Ex(9-39). Affinity to the glucagon-like peptide-1 receptor (GLP-1R) was evaluated with dispersed islet cells of ddY mice. Uptake of exendin(9-39) derivatives in the pancreas as well as in other organs was evaluated by a biodistribution study. Small-animal PET study was performed after injecting [18F]FB40-Ex(9-39). FB40-Ex(9-39) showed moderate affinity to the GLP-1R. Among all of the derivatives, [18F]FB40-Ex(9-39) resulted in the highest uptake of radioactivity in the pancreas 30 min after injection. Moreover, it showed significantly less radioactivity accumulated in the liver and kidney, resulting in an overall increase in the pancreas-to-organ ratio. In the PET imaging study, pancreas was visualized at 30 min after injection of [18F]FB40-Ex(9-39). [18F]FB40-Ex(9-39) met the basic requirements for an imaging probe for GLP-1R in pancreatic ß-cells. Further enhancement of pancreatic uptake and specific binding to GLP-1R will lead to a clear visualization of pancreatic ß-cells.

Japan Gastroenterological Endoscopy Society guidelines for endoscopic sphincterotomy.

The Japan Gastroenterological Endoscopy Society (JGES) has recently compiled guidelines for endoscopic sphincterotomy (EST) using evidence-based methods. Content regarding actual clinical practice, including detailed endoscopic procedures, instruments, device types and usage, has already been published by the JGES postgraduate education committee in May 2015 and, thus, in these guidelines we avoided duplicating such content as much as possible. The guidelines do not address pancreatic sphincterotomy, endoscopic papillary balloon dilation (EPBD), and endoscopic papillary large balloon dilation (EPLBD). The guidelines for EPLBD are planned to be developed separately. The evidence level in this field is often low and, in many instances, strong recommendation has to be determined on the basis of expert consensus. At this point in time, the guidelines are divided into six items including indications, techniques, specific cases, adverse events, outcomes, and postoperative follow up.

Synthesis and biological evaluation of an 111In-labeled exendin-4 derivative as a single-photon emission computed tomography probe for imaging pancreatic ß-cells.

A non-invasive method of pancreatic ß-cell mass measurement is needed to enhance our understanding of the pathogenesis of diabetes, facilitate the early diagnosis of this disease, and promote the development of novel therapeutics. Here, we described the synthesis of a novel indium-111 (111In) exendin-4 derivative, [Lys12(In-BnDTPA-Ahx)]exendin-4, through a process involving isothiocyanate-benzyl-DTPA (BnDTPA) and 6-aminohexanoic acid (Ahx) attached to an ɛ-amino group at the lysine-12 residue. We further evaluated the potential use of this derivative as a SPECT probe for pancreatic ß-cell imaging. An in vitro binding assay revealed that [Lys12(natIn-BnDTPA-Ahx)]exendin-4 has a high affinity for GLP-1 receptors (IC50=0.43nM). In biodistribution experiments involving normal mice, high [Lys12(111In-BnDTPA-Ahx)]exendin-4 uptake was observed in the pancreas (21.8 ± 4.0%ID/g) and was maintained for 2h after injection. Pre-injection of excess exendin(9-39) markedly reduced the pancreatic uptake of [Lys12(111In-BnDTPA-Ahx)]exendin-4 (95.2%), indicating that the uptake of this tracer is specific and mediated by GLP-1 receptors. Ex vivo autoradiography experiments involving pancreatic sections from MIP-GFP mice confirmed the accumulation of [Lys12(111In-BnDTPA-Ahx)]exendin-4 in pancreatic ß-cells. Finally, in mice, [Lys12(111In-BnDTPA-Ahx)]exendin-4 SPECT/CT yielded clear images of the pancreas at 30min post-injection. In conclusion, SPECT with [Lys12(111In-BnDTPA-Ahx)]exendin-4 enables to visualize ß-cells in vivo non-invasively.

Current status of interventional endoscopic ultrasound.

Endoscopic ultrasound (EUS) is being used increasingly in the management of pancreatic fluid collection, biliary and pancreatic duct drainage in cases of failed endoscopic retrograde cholangiopancreatography, drainage of the gallbladder, and other conditions. The role of interventional EUS is rapidly expanding and new interventions are continuously emerging. The development of devices could be a major breakthrough in the field of interventional EUS. New devices would enable the expansion of its role even further and prompt its widespread use in clinical practice. This review focuses on the current status of interventional EUS, especially highlighting the topics that are presently drawing the interest of endoscopists.