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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.

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.

Currently, quantifying β-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 β 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 β 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 β-cell mass with [111In]-labeled exendin-4.

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., Highlight Isayama and colleagues present the first clinical practice guidelines for endoscopic ultrasound‐guided biliary drainage (EUS‐BD), including indications, clinical results, procedures, devices and education. Their primary purpose is to improve the outcomes of EUS‐BD for biliary tract diseases by facilitating the safe introduction and performance of the procedure at non‐expert centers.

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.

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 40% of the volume of the whole pancreas enabled reliable estimates of uptake (%CV 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.

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.

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.

β-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 β-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 β-cells. Further enhancement of pancreatic uptake and specific binding to GLP-1R will lead to a clear visualization of pancreatic β-cells.

A non-invasive method of pancreatic β-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 β-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 β-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 β-cells in vivo non-invasively.

Aims/Introduction We investigated the association between four insulin regimens and increase in HbA1c and insulin dose in a real-life clinical setting because there is no data about them among insulin regimens. Materials and Methods Subjects 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 performed 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 subjects 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

Insulinoma is a tumor derived from pancreatic β-cells, and the resulting hyperinsulinemia leads to characteristic hypoglycemia. Recent studies have reported the frequent overexpression of glucagon-like peptide-1 receptor (GLP-1R) in human insulinomas, suggesting that the binding of a radiolabeled compound to GLP-1R is useful for the imaging of such tumors. Exendin(9-39), a fragment peptide of exendin-3 and -4, binds GLP-1R with high affinity and acts as an antagonist. Accordingly, radiolabeled exendin(9-39) derivatives have also been investigated as insulinoma imaging probes that might be less likely to induce hypoglycemia. In this study, we synthesized a novel indium-111 (111In)-benzyl-diethylenetriaminepentaacetic acid (111In-BnDTPA)-conjugated exendin(9-39), 111In-BnDTPA-exendin(9-39), and evaluated its utility as a probe for the SPECT imaging of insulinoma. natIn-BnDTPA-exendin(9-39) exhibited a high affinity for GLP-1R (IC50=2.5nM), stability in plasma, and a specific activity that improved following reactions with a solvent and solubilizer. Regarding the in vivo biodistribution of 111In-BnDTPA-exendin(9-39) in INS-1 tumor-bearing mice, high uptake levels were observed in tumors (14.6%ID/g at 15min), with corresponding high tumor-to-blood (T/B), tumor-to-muscle (T/M), and tumor-to-pancreas (T/P) ratios (T/B=2.55, T/M=22.7, T/P=2.7 at 1h). The pre-administration of excess nonradioactive exendin(9-39) significantly reduced accumulation in both the tumor and pancreas (76% and 68% inhibition, respectively) at 1h after 111In-BnDTPA-exendin(9-39) injection, indicating that the GLP-1R mediated a majority of 111In-BnDTPA-exendin(9-39) uptake in the tumor and pancreas. Finally, 111In-BnDTPA-exendin(9-39) SPECT/CT studies in mice yielded clear images of tumors at 30min post-injection. These results suggest that 111In-BnDTPA-exendin(9-39) could be a useful SPECT molecular imaging probe for the detection and exact localization of insulinomas.

Currently, quantifying β-cell mass (BCM) requires harvesting the pancreas. In this study, we investigated a potential noninvasive method to quantify BCM changes longitudinally using [Lys(12)((111)In-BnDTPA-Ahx)]exendin-4 ([(111)In]-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 [(111)In]-Ex4 toward β cells. Using nonobese diabetic (NOD) mice, we injected [(111)In]-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 [(111)In]-Ex4 in β 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 [(111)In]-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 β-cell mass with [(111)In]-labeled exendin-4.

Longitudinal observation of pancreatic β-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.

Aims: For the purpose of visualization and quantification of β cells, glucagon-like peptide 1 receptor (GLP-1R)-targeting imaging including single photon emission computed and positron emission tomography (SPECT/PET) has emerged recently. It is well known that internalization of the probes can affect visualization of regions of interest on SPECT/PET. However, the internalization and its effect on β-cell visualization of GLP-1R-targeting probes have not been fully examined. Therefore, we investigated time-based internalized activities of an exendin-4 (Ex4)-based probe, which was developed for clinical GLP-1R-targeting imaging. Method: [18F]FB(ePEG12)12-Ex4 (18F-Ex4) was synthesized. Rat insulinoma cell line, INS-1 and Human Embryonic Kidney cells 293 expressing human GLP-1R (HEK_GLP-1R) were used as GLP-1R-positive cells. These cells were incubated with 18F-Ex4 (1.48 MBq) for different periods of time (0-120 minutes). Whole cell (WC) and internalized (IC) radioisotope activities were measured by the gamma counter. Results: WC per incubated probe (IP) activities showed rapid rise within 30 minutes of incubation time and further gradual increase up to 120 minutes in INS-1 and HEK_GLP-1R cells, whereas wild type HEK293 showed no significant WC activity. The WC/IP differences between INS-1 and HEK_GLP-1R cells were significant at the 15-minutes mark (p=0.04) but reduced to insignificant after 30 minutes, although the two cell lines showed significantly different levels of GLP-1R mRNA expressions. IC/IP increased rapidly within 30 minutes and gradually up to 120 minutes. The IC/WC at the 120-minutes mark were significantly higher than those at the 30-minutes mark in both cell lines. Conclusion: The 18F-Ex4 probe showed rapid uptakes and internalization in GLP-1R-expressing cell lines, which indicates that dual or delayed phases of GLP-1R-targeting imaging may be beneficial. In addition, a time-based hampering effect of GLP-1R-expression levels for β-cell visualization can be suggested. Disclosure T. Murakami: None. H. Fujimoto: None. N. Fujita: None. K. Hamamatsu: None. J. Fujikura: None. N. Inagaki: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Japan Tobacco Inc., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited.

Aims:Type 2 diabetes mellitus (T2DM) is known as a progressive disease with loss of pancreatic β-cell mass (BCM) and functions. However, longitudinal changes of BCM remain veiled since non-invasive techniques for observation of BCM in vivo have not been established. We developed [Lys12(111In-BnDTPA-Ahx)]exendin-4 (111In-Ex4) targeting a glucagon-like peptide 1 (GLP-1) receptor, which enabled to quantify BCM non-invasively. DS8500a, a G protein-coupled receptor 119 (GPR119) agonist, is under investigation for the treatment of T2DM. Some GPR119 agonists showed the possible stimulation of β-cell replication, which suggested some preferable effects of GPR119 agonists on BCM. Therefore, we investigated this GPR119 agonist effect on BCM in diabetic mice using our 111In-Ex4 SPECT/CT technique. Method: Five-week-old male db/db mice with dietary restriction were assigned to the following two groups: mice fed with normal chaw (group C) and those with DS8500a-mixed chaw (group DS). We performed 111In-Ex4 SPECT/CT every four weeks until 13 weeks old and evaluated the RI accumulations in the pancreas. Ex-vivo pancreatic RI intensities, together with pathological and immunohistochemical analysis of BCM were also examined. Results: As for 111In-Ex4 SPECT/CT, pancreatic RI intensities in group DS were significantly higher than those of group C, at the age of 9 and 13 weeks old. Moreover, ex-vivo pancreatic RI intensities in group DS were significantly higher than those of group C. Pathological BCM analysis revealed significantly larger BCM in group DS than in group C. Conclusion: 111In-Ex4 SPECT/CT as wells as ex-vivo pancreatic analysis showed preserved BCM in mice with DS8500a. This result was corroborated by the conventional pathological method. Taken together, 111In-Ex4 SPECT/CT showed DS8500a, a GPR119 agonist, could attenuate the progression of BCM loss in diabetic mice. Disclosure T. Murakami: None. H. Fujimoto: None. N. Fujita: None. K. Hamamatsu: None. K. Matsumoto: None. N. Inagaki: Research Support; Self; Daiichi Sankyo Company, Limited, AstraZeneca, Ono Pharmaceutical Co., Ltd., Sanofi K.K., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited, Japan Tobacco Inc., MSD K.K., Sumitomo Dainippon Pharma Co., Ltd., Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Kissei Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., Eli Lilly and Company, Sanwa Chemical Industrial Co., Ltd., Teijin Pharma Limited.

Background: Defects in insulin secretory function can be divided into two elements, the dysfunction of individual beta cells and a decrease of beta cell mass (BCM). Non-invasive methods to quantify BCM have not yet been established, and thus it is not possible to observe longitudinal changes in BCM. We developed [Lys12(111In-BnDTPA-Ahx)]exendin-4 ([111In]Ex4) as a radioactive probe targeting to the glucagon-like peptide-1 receptor with the aim of quantifying BCM by the measurement of probe accumulation in the pancreas. In this study, we investigated the protective effect of sodium-glucose co-transporter-2 (SGLT2) inhibitor on BCM using in-vivo SPECT/CT imaging with this probe. Aim: We tried to investigate longitudinal change in BCM of diabetic model mice administered with SGLT2 inhibitor using in-vivo SPECT/CT imaging with [111In]Ex4. Method: Male db/db mice were assigned into two groups: canagliflozin-administered group (group A) and non-administration group (group B). In-vivo SPECT/CT scans were performed before and after the intervention. The pancreatic uptake of [111In]Ex4 was evaluated using ROI with > 40% of the volume of the whole pancreas with the exception of the perirenal space. Result: The pancreatic uptake was significantly decreased in group B, on the other hand, no significant change was observed in group A. After the intervention, the pancreatic uptake was significantly higher in group A than group B. Discussion: SPECT/CT imaging analysis indicated that BCM was significantly larger in group A than group B after the intervention. It is considered that this difference was made by the protective effect of canagliflozin on BCM. Conclusion: It is considered that the protective effect of canagliflozin on BCM could be investigated using in-vivo SPECT/CT imaging with [111In]Ex4. Disclosure K. Hamamatsu: None. H. Fujimoto: None. N. Fujita: None. T. Murakami: None. M. Shiotani: Employee; Self; Mitsubishi Tanabe Pharma Corporation. H. Saji: Research Support; Self; Nihon Medi-Physics Co.,Ltd. N. Inagaki: Research Support; Self; Daiichi Sankyo Company, Limited, AstraZeneca, Ono Pharmaceutical Co., Ltd., Sanofi K.K., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited, Japan Tobacco Inc., MSD K.K., Sumitomo Dainippon Pharma Co., Ltd., Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Kissei Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., Eli Lilly and Company, Sanwa Chemical Industrial Co., Ltd., Teijin Pharma Limited.

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.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.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 with40% 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 ± 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).Our analytical method without nephrectomy or additional probes enables reliable quantification of the pancreatic uptake of

In addition to surgery, procedures for patients with pancreatolithiasis are developing; therefore, establishing practical guidelines for the management of pancreatolithiasis is required.Three committees (the professional committee for asking clinical questions (CQs) and statements by Japanese endoscopists, the expert panel committee for rating statements by the modified Delphi method, and the evaluating committee by moderators) were organized. Eight endoscopists and a surgeon for pancreatolithiasis made the CQs and statements from a total of 694 reports of published literature by PubMed search (from 1983 to 2012). The expert panelists individually rated these clinical statements using a modified Delphi approach, in which a clinical statement receiving a median score greater than 7 on a 9-point scale from the panel was regarded as valid.The professional committee made 3, 7, and 10 CQs and statements for the concept and pathogenesis, diagnosis, and treatment, respectively. The expert panelists regarded them as valid after a 2-round modified Delphi approach.After evaluation by the moderators, the Japanese clinical guidelines for pancreatolithiasis were established. Further discussions and studies for international guidelines are needed.

β-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

A non-invasive method of pancreatic β-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 (

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.

Background and Aim To assess the usefulness of the thread-traction method (TT method) in esophageal endoscopic submucosal dissection (ESD). Methods A total of 40 lesions that were scheduled to be treated by esophageal ESD were included in the study. The TT method was used for 20 lesions (group TT) and conventional ESD was used for 20 lesions (group C) after randomization. The hook-knife method was used in all cases. In group TT, after circumferential mucosal incision, a clip with thread was attached to the oral edge of the lesion. Results ESD was carried out in all cases. Effective countertraction was created by the TT method, and it was possible to carry out an efficient dissection operation. Significant shortening of dissection time was achieved in group TT compared with group C (19.8 min vs 31.8 min, P = 0.044). Mean number of local injections during dissection was significantly less in group TT compared with that in group C (0.6 times vs 2.2 times, P

The purpose of this study is to prospectively assess whether direct visualization of pancreatic juice flow using an unenhanced MRI technique with spin labeling can aid in the diagnosis of chronic pancreatitis.Ten healthy volunteers and 50 patients who were categorized as having no chronic pancreatitis (n = 11), early chronic pancreatitis (n = 7), or established chronic pancreatitis (n = 32) underwent MRI, including direct pancreatic juice visualization using a flow-out technique with a time-spatial labeling inversion pulse, comprising a nonselective inversion recovery pulse immediately followed by a spatially selective inversion labeling pulse. The mean velocities and volumes of pancreatic juice excretion were also obtained. Variance tests were used to evaluate the clinical groups with respect to the appearance rate and mean velocity; the Kruskal-Wallis test was used for volume.There were no significant differences between healthy volunteers and patients with no chronic pancreatitis. The appearance rate, mean velocity, and volume of pancreatic juice excretion tended to decrease with the degree of chronic pancreatitis. Although the difference in these values was statistically significant between the healthy group and the established chronic pancreatitis group, the values of the early group and other groups were not statistically significant. There was a significant correlation between the appearance rate of pancreatic juice and the clinical groups (τ = -0.4376, p = 0.0015).The measurement of directly visualized pancreatic juice flow may aid in establishing the diagnosis of chronic pancreatitis.

According to the international consensus guidelines 20121 for the management of intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms of the pancreas, main duct IPMN (MD-IPMN) and branch duct IPMN (BD-IPMN) are significantly different with regard to the prevalence of carcinoma, and therefore, the classification has prognostic implications. When MD-IPMN is diagnosed in a patient, surgical treatment should be considered. In BD-IPMN, however, it is important to differentiate low-grade dysplasia from high-grade dysplasia (carcinoma in situ) or ordinary invasive pancreatic ductal adenocarcinoma (PDAC) to avoid excessive surgery. The presence of mural nodules (MNs) has reportedly been the most important factor for predicting malignancy and determining the indication for surgery of BD-IPMN. However, there is a paucity of data on the morphological and histologic changes in patients with BD-IPMN with MNs during follow-up. The aim of this study was to evaluate long-term follow-up results of patients with BD-IPMN who had MNs on initial imaging in a retrospective multicenter series for better management of patients with BD-IPMN.

Autoimmune pancreatitis (AIP) must be differentiated from pancreatic carcinoma, and immunoglobulin (Ig)G4-related sclerosing cholangitis (SC) from cholangiocarcinoma and primary sclerosing cholangitis (PSC). Pancreatographic findings such as a long narrowing of the main pancreatic duct, lack of upstream dilatation, skipped narrowed lesions, and side branches arising from the narrowed portion suggest AIP rather than pancreatic carcinoma. Cholangiographic findings for PSC, including band-like stricture, beaded or pruned-tree appearance, or diverticulum-like outpouching are rarely observed in IgG4-SC patients, whereas dilatation after a long stricture of the bile duct is common in IgG4-SC. Transpapillary biopsy for bile duct stricture is useful to rule out cholangiocarcinoma and to support the diagnosis of IgG4-SC with IgG4-immunostaining. IgG4-immunostaining of biopsy specimens from the major papilla advances a diagnosis of AIP. Contrast-enhanced endoscopic ultrasonography (EUS) and EUS elastography have the potential to predict the histological nature of the lesions. Intraductal ultrasonographic finding of wall thickening in the non-stenotic bile duct on cholangiography is useful for distinguishing IgG4-SC from cholangiocarcinoma. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is widely used to exclude pancreatic carcinoma. To obtain adequate tissue samples for the histological diagnosis of AIP, EUS-Tru-cut biopsy or EUS-FNA using a 19-gauge needle is recommended, but EUS-FNA with a 22-gauge needle can also provide sufficient histological samples with careful sample processing after collection and rapid motion of the FNA needles within the pancreas. Validation of endoscopic imaging criteria and new techniques or devices to increase the diagnostic yield of endoscopic tissue sampling should be developed.

We herein report a case of intracholecystic papillary-tubular neoplasm (ICPN) of the gallbladder in which jaundice developed. A 58-year-old woman with jaundice was referred to our hospital. Computed tomography revealed a papillary tumor in the body of the gallbladder protruding into the bile duct. A transpapillary biopsy of the bile duct verified adenocarcinoma, and pancreatoduodenectomy with extended cholecystectomy was performed. The tumor spread macroscopically from the gallbladder body to the cystic duct, thus forming a polypoid mass protruding into the bile duct. This is a rare case of invasive carcinoma from ICPN leading to mechanical obstruction of the bile duct.

A 44-year-old man with type 2 diabetes of five years' duration was admitted for the management of poor glycemic control despite the administration of insulin therapy. On admission, he received vigorous treatment for a 28-year history of Crohn's disease and a 14-year history of a psychiatric disorder. His glycosylated hemoglobin A1c (HbA1c) level was 11.3%, his fasting blood glucose level was 567 mg/dL and his C-peptide level was 1.0 ng/mL. His quality of life (QOL) was severely impaired as a result of frequent episodes of hyperglycemia and hypoglycemia. Treatment with liraglutide was commenced in place of insulin, which improved the patient's glycemic control to an HbA1c level of 5.5% and markedly increased his QOL score with no hypoglycemia.

Background and Aim Although biliary cannulation with pancreatic guidewire placement (P-GW) is useful for difficult cases in endoscopic retrograde cholangiopancreatography (ERCP), the clinical significance of wire-guided cannulation with P-GW (double-guidewire technique: DGT) has not been clarified. The aim of the present study was to evaluate the usefulness of DGT for difficult biliary cannulation after unsuccessful biliary cannulation using a cannula/sphincterotome under guidance of injected contrast with P-GW (single-guidewire technique: SGT). Methods One-hundred and forty-six patients with difficult biliary cannulation who underwent SGT were included in this retrospective study. DGT was carried out if SGT was unsuccessful. Pancreatic duct (PD) stenting was attempted to prevent post-ERCP pancreatitis (PEP) in all patients. The success rate of cannulation and the risk factors for PEP were investigated. Results Biliary cannulation with SGT was achieved in 70%. DGT was carried out in 25 patients with unsuccessful SGT, biliarycannulation being successful in 72%. Of the 13 patients who underwent precut sphincterotomy, biliary cannulation was achieved in 46%. The incidence of PEP in patients who had undergone SGT, DGT, and precut sphincterotomy was 8% (12: mild, 8; moderate, 3; severe, 1), 4% (mild, 1), and 0%, respectively. PD stenting was successfully carried out in 86%. Multivariate analysis revealed unsuccessful PD stenting to be the only risk factor for PEP (OR 8.3, 95% CI 2.3–30). Conclusions DGT may replace SGT or become the salvage procedure in cases of unsuccessful SGT as a result of its high success rate with an acceptable incidence of PEP. Failed pancreatic duct stenting in these techniques was frequently associated with PEP.

Aims To evaluate diurnal patterns of plasma glucose in Japanese patients with type 2 diabetes receiving sulfonylurea and the effectiveness of daily premixed biphasic insulin analog (insulin lispro mix 50/50) injections plus sulfonylurea before breakfast (Mid mixture insulin analog-supported Oral Therapy, MOT).

Pancreatobiliary reflux (PBR) can occur in individuals without pancreaticobiliary maljunction. The aim of this study was to elucidate the incidence of PBR in individuals with a normal pancreaticobiliary junction and its impact on the biliary tree.Data were prospectively collected from 15 centers on 420 patients with a morphologically normal pancreaticobiliary junction who had undergone bile sampling and measurement of the biliary amylase level. We investigated the incidence and predictive factors for high biliary amylase levels (HBAL), as well as the relationship of HBAL with biliary malignancy.Twenty-three patients (5.5%) showed HBAL (≥10,000 IU/L). Univariate analysis showed that risk factors for the elevation of biliary amylase levels were the existence of a relatively long common channel (≥5 mm), acute pancreatitis, and papillitis. Multivariate analysis revealed that only the existence of a relatively long common channel was a significant factor for PBR. Biliary amylase levels in patients with a relatively long common channel were significantly higher than in patients without a long common channel (12,333 vs. 2,070 IU/L, P = 0.001). The incidence of HBAL (P0.001), as well as the overall biliary amylase levels (P = 0.007) were significantly higher in patients with gallbladder cancer than in those without gallbladder cancer.The PBR was frequently observed in individuals with a relatively long common channel. Patients showing HBAL with normal pancreaticobiliary junction are at high risk for gallbladder cancer.

We herein report a rare case of very small Barrett's adenocarcinoma. A 65-year-old man underwent surveillance esophagogastroduodenoscopy (EGD) 3 years after endoscopic submucosal dissection (ESD) for superficial Barrett's adenocarcinoma, which revealed a very small reddish area in the mucosa, 2 mm in diameter, in long-segment Barrett's esophagus. The EGD carried out 1 year later confirmed slight enlargement of the lesion, from 2 mm to 3 mm in diameter. Macroscopic type changed from flat type to slightly depressed type. On narrow-band imaging with magnifying endoscopy, an irregular microstructure and irregular microvasculature became recognizable. It was resected by ESD and diagnosed as mucosal adenocarcinoma with a diameter of only 3 mm.

A metal stent has a longer stent patency than a plastic stent in patients with unresectable malignant distal biliary stricture. However, treatment for stent dysfunction of a metal stent remains unresolved. A review of reported articles regarding reintervention for metal stent dysfunction showed that causes of stent dysfunction included tumor ingrowth/overgrowth, stone/sludge/food impaction, and stent migration. Cleaning of the stent is associated with an early relapse of stent dysfunction. Additional placement of a covered metal stent is expected to have a longer stent patency than that of other stents such as uncovered metal stents or plastic stents. It is recommended that occluded covered metal stents be removed if possible. Stent trimming with argon plasma coagulation is sometimes useful for the treatment of stent displacement. No strategy for occluded metal stents has been established yet. Further clinical trials regarding proper treatments are necessary.

To prospectively evaluate the role of contrast-enhanced computed tomography (CE-CT) in the detection of colonic diverticular bleeding (CDB).Consecutive patients who presented with hematochezia and were clinically suspected of CDB were prospectively enrolled. Those who could undergo both CE-CT and total colonoscopy, and who were finally diagnosed as CDB, were included in the analysis.Fifty-two cases were finally included in the analysis. The detection rate of CDB by CT was 15.4 % (8/52). Univariate analysis showed that the interval from the latest episode of hematochezia to the performance of CT and the presence of a past history of CDB were contributing factors for detection. The interval was 1.6 ± 4.6 h (mean ± SD) in patients detected by CT, and 3.4 ± 3.2 h in those without detection. The detection rate of CDB by total colonoscopy was 38.5 % (20/52). The overall detection rate was 46.2 % (24/52), which was superior to what CT or colonoscopy alone achieved.CE-CT may play a complementary role to colonoscopy in patients with suspected CDB, but is not recommended for all cases due to its low detection rate. Patients who can be examined within 2 h of last hematochezia would be candidates for urgent CT.

Cholelithiasis is one of the commonest diseases in gastroenterology. Remarkable improvements in therapeutic modalities for cholelithiasis and its complications are evident. The Japanese Society of Gastroenterology has revised the evidence-based clinical practice guidelines for cholelithiasis. Forty-three clinical questions, for four categories—epidemiology and pathogenesis, diagnosis, treatments, and prognosis and complications—were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases for the period between 1983 and June 2012. The guidelines were developed with use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. This article preferentially describes the clinical management of cholelithiasis and its complications. Following description of the diagnosis performed stepwise through imaging modalities, treatments of cholecystolithiasis, choledocholithiasis, and hepatolithiasis are introduced along with a flowchart. Since there have been remarkable improvements in endoscopic treatments and surgical techniques, the guidelines ensure flexibility in choices according to the actual clinical environment. The revised clinical practice guidelines are appropriate for use by clinicians in their daily practice.

Genetic factors are important determinants of the onset and progression of diabetes mellitus. Numerous susceptibility genes for type 2 diabetes, including potassium voltage-gated channel, KQT-like subfamily Q, member1 (KCNQ1), have been identified in humans by genome-wide analyses and other studies. Experiments with genetically modified mice have also implicated various genes in the pathogenesis of diabetes. However, the possible effects of the parent of origin for diabetes susceptibility alleles on disease onset have remained unclear. Here, we show that a mutation at the Kcnq1 locus reduces pancreatic β-cell mass in mice by epigenetic modulation only when it is inherited from the father. The noncoding RNA KCNQ1 overlapping transcript1 (Kcnq1ot1) is expressed from the Kcnq1 locus and regulates the expression of neighboring genes on the paternal allele. We found that disruption of Kcnq1 results in reduced Kcnq1ot1 expression as well as the increased expression of cyclin-dependent kinase inhibitor 1C (Cdkn1c), an imprinted gene that encodes a cell cycle inhibitor, only when the mutation is on the paternal allele. Furthermore, histone modification at the Cdkn1c promoter region in pancreatic islets was found to contribute to this phenomenon. Our observations suggest that the Kcnq1 genomic region directly regulates pancreatic β-cell mass and that genomic imprinting may be a determinant of the onset of diabetes mellitus.

Insulinoma is a tumor derived from pancreatic β-cells, and the resulting hyperinsulinemia leads to characteristic hypoglycemia. Recent studies have reported the frequent overexpression of glucagon-like peptide-1 receptor (GLP-1R) in human insulinomas, suggesting that the binding of a radiolabeled compound to GLP-1R is useful for the imaging of such tumors. Exendin(9-39), a fragment peptide of exendin-3 and -4, binds GLP-1R with high affinity and acts as an antagonist. Accordingly, radiolabeled exendin(9-39) derivatives have also been investigated as insulinoma imaging probes that might be less likely to induce hypoglycemia. In this study, we synthesized a novel indium-111 (

Aim To evaluate the effect of wire-guided biliary cannulation (WGC) on the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Methods We investigated the impact of the WGC technique on the incidence of PEP by comparing the conventional cannulation (CC) technique in selective bile duct cannulation during ERCP with a cross-over design in a prospective multicenter randomized controlled trial and the potential risk factors for PEP. This involved six tertiary referral centers and three university hospitals. A total of 322 patients with indications for ERCP requiring selective biliary cannulation were enrolled from April 2008 to March 2009. Results One hundred and sixty-three patients were assigned to the WGC group and 159 to the CC group. The incidence of PEP was the same between the groups (6.1% vs 6.3%, P = 0.95). Primary successful biliary cannulation was achieved in 136 patients (83%) in the WGC group and in 138 (87%) in the CC group (P = 0.40). The mean time required for primary successful biliary cannulation was 7.4 ± 8.3 min and 7.2 ± 7.9 min, respectively (P = 0.83). Multivariate analysis demonstrated that accidental guidewire insertions and unintended injections of contrast into the main pancreatic duct were the only independent risk factors for PEP (P = 0.001, relative risk [RR]: 8.70, 95% confidence interval [CI]: 2.46–30.81). Conclusion The WGC technique does not reduce the risk of PEP and also does not improve the success rate of selective bile duct cannulation.

Recently, the clinical application of diffusion-weighted magnetic resonance imaging (DWI) has been expanding to abdominal organs. However, only a few studies on gallbladder diseases have been published. The aim of this study was to evaluate the usefulness and limitations of high b-value DWI for gallbladder diseases. A total of 153 patients (mean age 60 ± 15 years, 78 males) who had undergone DWI for evaluating gallbladder wall thickening or polypoid lesions were included in this study. Of these 153 patients, 36 had gallbladder cancer and 117 had benign gallbladder diseases (67 chronic cholecystitis, 44 adenomyomatosis, four cholesterol polyp, one gallbladder adenoma, and one xanthogranulomatous cholecystitis). We evaluated the positive signal rate with DWI and the apparent diffusion coefficient (ADC) value of each disease. The positive signal rate with DWI was significantly higher in gallbladder cancer (78 %) than in benign gallbladder diseases (22 %) (p

Background and Aim: Although reports on endosonography-guided biliary drainage (ESBD) have been increasing, only a few reports on deployment of a self-expandable metal stents (SEMS) have been reported. The aim of the present study was to evaluate the safety and efficacy of SEMS deployment in ESBD. Methods: Of 42 patients who underwent ESBD during the period from January 2007 to August 2011, 21 patients with unresectable malignant biliary obstruction in whom SEMS deployment had been attempted were included. In the first session, a plastic stent or SEMS was placed in a bilio-enteric anastomosis (BEA) method. SEMS was deployed with the one-step technique or with replacement of a plastic stent with a SEMS in the second session. The technical success, early and late complications, and stent patency of SEMS were evaluated. Results: One-step SEMS deployment was attempted in seven patients, and SEMS was deployed with stent exchange in 14. SEMS deployment was successful in all patients without any complications. Finally, SEMS was placed in a BEA method in 16 patients (extrahepatic bile duct, 13; intrahepatic bile duct, three), and with antegrade deployment in five. Late complications occurred in three patients who underwent deployment of SEMS in a BEA method (stent obstruction in two and reflux cholangitis in one). The mean stent patency period was 433 days. Conclusions: As SEMS deployment in ESBD is safe and provides long stent patency, a SEMS seems to be the stent of choice in ESBD for patients with unresectable malignant biliary obstruction in whom long survival is expected.

The causes of benign biliary stricture include chronic pancreatitis, primary/immunoglobulin G4-related sclerosing cholangitis and complications of surgical procedures. Biliary stricture due to fibrosis as a result of inflammation is sometimes encountered in patients with chronic pancreatitis. Frey's procedure, which can provide pancreatic duct drainage with decompression of biliary stricture, can be an initial treatment for chronic pancreatitis with pancreatic and bile duct strictures with upstream dilation. When patients are high-risk surgical candidates or hesitate to undergo surgery, endoscopic treatment appears to be a potential second-line therapy. Placement of multiple plastic stents is currently considered to be the best choice as endoscopic treatment for biliary stricture due to chronic pancreatitis. Temporary placement with a fully covered metal stent has become an attractive option due to the lesser number of endoscopic retrograde cholangiopancreatography (ERCP) sessions and its large diameter. Further clinical trials comparing multiple placement of plastic stents with placement of a covered metal stent for biliary stricture secondary to chronic pancreatitis are awaited.

There have been only a few reports on follow-up results of serous cystic neoplasm (SCN) of the pancreas. The frequency of malignancy and surgical indication of SCN are not determined yet.In this multi-institutional study of the Japan Pancreas Society, a total of 172 patients with SCN were enrolled. The mean follow-up period was 4.5 years. Surgical resection was performed in 90 patients, whereas the remaining 82 were simply observed.Of all patients, 20% were symptomatic. The tumor was located in the pancreatic head (39%), body (35%), and tail (22%). The mean diameter of the tumor was 4.1 cm. None of the patients showed distant or lymph node metastasis except for liver metastasis found in 2 patients (1.2%). No patient died during the follow-up. The preoperative diagnosis did not correctly identify SCN in 57 (63%) of 90 resected cases. A honeycomb appearance, which is one of the most characteristic findings of SCN, could be diagnosed better by endoscopic ultrasonography than by other imaging diagnostic modalities.Surgical resection should be considered only when clear distinction from other surgical diseases is difficult, when symptoms or mass effects are present, and when the tumor size is large.

Aim: Endoscopic diagnosis of the lateral extension of Barrett's cancer under the squamous epithelium (BCUS) is sometimes difficult because the cancer is unobservable in the esophageal lumen. The aim of the present study was to clarify the endoscopic features of the extension of BCUS and verify the usefulness of the acetic acid-spraying method (AAS) for diagnosis. Methods: A total of 25 patients with Barrett's cancer who had undergone endoscopic resection were included in this study. Histological examination of patients' resected specimens was performed to identify the presence of BCUS. Then, the endoscopic images of the BCUS cases were reviewed to summarize the findings and to evaluate the feasibility of diagnosing the extent of BCUS with each imaging technique. Results: Of the 25 patients, 10 (40%) had BCUS. With white-light imaging, subtle reddish change was observed in the area of BCUS in 80% of the patients, and a flat elevated lesion was recognized in 30%. With narrow band imaging, slight brownish change was observed in the area of BCUS in 86% of the patients. Slight white changes were visualized in all cases with AAS. The extension of BCUS was correctly diagnosed by white-light imaging, narrow band imaging and AAS in 50%, 43% and 100% of the cases, respectively. Histology verified the opening of cancerous glands, which extended under the squamous epithelium, into the esophagus in the area showing slight white changes by AAS. Conclusion: AAS can be useful for diagnosing the extension of BCUS.

Purpose: To visualize the movement of pancreatic juice noninvasively by using an unenhanced magnetic resonance (MR) imaging technique. Materials and Methods: Institutional review board approval and informed consent were obtained for this study. A flow-out technique of time-spatial labeling inversion pulse (SLIP) technique was applied using both nonselective and selective inversion pulses to label, or tag, pancreatic juice to move out of the region. Ten normal (eight men, two women; age range, 22–61 years; mean age, 35 years) and two pathologic conditions were examined on a commercially available 1.5 Tesla MR imager with quadrature-detected phased-array coils. All images were evaluated by two radiologists to assess depiction of the pancreatic juice movement or pancreatic juice reflux as compared to the pancreatic duct or the common bile duct on MRCP obtained before time-SLIP examination. Results: The tagged pancreatic juice was satisfactory visualized after applying the pulse labeling. Noninvasive visualization of pancreatic juice movement, including normal pancreatic juice movement and reflux from the main pancreatic duct into the common bile duct, was possible by using the unenhanced time-SLIP technique. Conclusion: Noninvasive visualization of pancreatic juice movement is possible by using the unenhanced MR imaging time-SLIP technique. J. Magn. Reson. Imaging 2012;35:1019-1124. © 2011 Wiley Periodicals, Inc.

Aims/Introduction: A method of estimating HbA1c attained after initiation of basal supported oral therapy (BOT) has not been reported previously. The aim of the present study was to determine which characteristics of patients could influence the effectiveness of BOT introduction, and to obtain an equation to estimate HbA1c after BOT initiation. Materials and Methods: Sixty consecutive insulin-naive type 2 diabetic patients with poor glycemic control (HbA1c ≥7.5%) started once-daily injections of insulin glargine. Simple correlations were calculated between parameters such as HbA1c at baseline, HbA1c at week 24, reduction rate of HbA1c over 24 weeks (calculated as: [HbA1c level at baseline – HbA1c level at week 24]/HbA1c level at baseline), duration of diabetes, and the number of classes of coadministered oral antidiabetic drugs. Using multiple linear regression models, the independent effects of these parameters on HbA1c at week 24 were evaluated separately. Results: Multiple linear regression analysis revealed that duration of diabetes (β = 0.561; P

Aim: To elucidate the diagnostic efficacy of the cell block (CB) method by comparing it with that of conventional smear cytology for pancreatic juice obtained by endoscopic retrograde cholangiopancreatography (ERCP) in a randomized controlled trial fashion. Methods: A total of 170 patients with pancreatic lesions suspicious of being malignant who underwent pancreatic juice collection without giving secretin under ERCP were enrolled in this study. After sampling, the pancreatic juice was randomized to the CB method (n = 85) or to smear cytology (n = 85). CB sections were subjected to hematoxylin-eosin, periodic acid Schiff–Alcian blue, and immunohistochemical stains. Both Papanicolaou stain and Giemsa stain were used for smear cytology. Results: The final diagnosis was malignancy in 54 patients: pancreatic cancer, 45; intraductal papillary-mucinous carcinoma, six; and endocrine tumor, three. The number of patients with a cytological borderline malignancy in the CB group (3.5%) was significantly smaller than that in the smear group (27.1%) (P

Aim: To evaluate the usefulness of a modified technique of endoscopic papillectomy (EP) for lessening the occurrence of complications. Methods: Indications for EP were adenoma or well-differentiated adenocarcinoma confined to the papilla of Vater (T1) without tumor spread into the bile/pancreatic duct. Sixteen patients underwent the modified technique, which consists of resection with the Endocut® mode, followed by biliary/pancreatic sphincterotomy and stenting (Group A). Twelve patients who had undergone EP, using a cutting current, followed by pancreatic duct stenting were included as control (Group B). The frequency of complications and clinical outcomes were retrospectively compared between the two groups. Results: Sixteen patients had adenoma, and 12 had adenocarcinoma. Early complications occurred in 36% of all patients (hemorrhage, 7; cholangitis, 3; perforation, 2; cholecystitis, 1). The frequency of early complications in Group A was significantly lower than that in Group B (6% vs 75%, odds ratio [OR] 0.022, 95% confidence interval [CI], 0.0020–0.25). Late complications occurred in 18% of the patients (bile duct stone, 3; hemorrhage, 1; pancreatitis, 1). There was no significant difference in the late complication rate between Group A and Group B (19% vs 17%). Local recurrences were found in 14% of the patients, without a significant difference between Group A and Group B (19% vs 8%) during a mean follow-up period. All recurrent tumors were successfully treated with argon plasma coagulation. Conclusions: The modified technique of EP for ampullary neoplasm contributed to lessening the occurrence of early complications. However, further refinement of this technique is necessary for improving the clinical outcome.