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A peroral cholangioscope (POCS) can allow direct visualization of the biliary mucosa and its use is becoming more widespread due to improvements in functionality, image quality, and operability, as well as the development of related devices. Recently, a novel mother-baby peroral cholangioscope (nMB-POCS) with a large (2-mm) accessory channel has been developed. In this study, we evaluated the feasibility of this novel POCS in a dry simulation and animal model.We evaluated the ease of insertion and maneuverability of the nMB-POCS, the image quality, and the passage of the devices into the accessory channel and into the common bile duct in a dry and live porcine model.In both models, the nMB-POCS could be easily inserted into the duodenoscope and into the distal bile duct and hilum. The image quality was good, and it was possible to observe the surface structure and the vascular network of the bile duct mucosa in detail.The nMB-POCS with its larger accessory channel is expected to improve the efficiency of diagnosis and treatment, and reduce the procedure time. Clinical studies in patients are warranted.

Shear wave elastography (SWE) is a clinical method used to evaluate liver hardness. In this study, we assessed its applicability in assessing the pancreas and its potential for diagnosing chronic pancreatitis.We performed SWE on 59 patients who underwent abdominal ultrasound, and measured the computed tomography (CT) values of the pancreas. Patients were classified as having a normal pancreas (NP), early chronic pancreatitis (ECP), or chronic pancreatitis (CP). SW elasticity (SWe), SW dispersion (SWd), and CT values between groups were analyzed.SWe significantly differed between the CP and NP/ECP groups (NP vs CP; P = 0.001, ECP vs CP; P = 0.026,), while SWd showed a significant difference only between the NP and CP group (NP vs CP; P = 0.001). The CT values were significantly different between the CP and NP/ECP groups (NP vs CP; P = 0.0006, ECP vs CP; P = 0.0027).Pancreatic SWE and CT values were helpful in the diagnosis of chronic pancreatitis. SWd may reveal status changes in ECP.

The crystallinity of cellulose decreases when bundled microfibrils are dispersed in water as cellulose nanofibers (CNFs) or physically separated into finer nanoscale fibrils or single microfibrils. The crystallinity of these CNFs is recovered when they become densely assembled through the dehydration of the dispersion. In this process, multiple CNFs are assumed to partially fuse, leading to the enlargement of crystallite widths. The mechanism of this CNF fusion is, however, not well understood. In this study, the recovery process of the crystallinity of CNFs was monitored by sampling wet CNF gels during condensation from a dilute dispersion to a dense aggregate, followed by wide-angle X-ray diffractometry (WAXD) and solid-state 13C nuclear magnetic resonance (NMR) spectroscopy analyses after supercritical drying. In the WAXD analysis, a two-step enlargement in the (2 0 0) crystal size was observed: the first step was a rapid increase in the range of solid content up to 1%, followed by a gradual increase in the range of 1–85%. The crystallinity index estimated by NMR hardly changed in the range of 0.5–30% but gradually increased in the range of 30–85%. A portion of the CNF samples, without drying, were also subjected to small-angle X-ray scattering and viscoelasticity analyses, indicating that the inter-CNF contact points in water significantly increased until reaching a solid content of 1%, and then at solid contents higher than 1%, the contact areas of each point gradually expanded. Finally, a mechanism of CNF fusion was proposed based on these results.

Background and Aims The optimal electrosurgical unit (ESU) settings for endoscopic papillectomy (EP) have not been investigated. We conducted animal experiments to determine the optimal endoCUT settings with VIO (Erbe, Tubingen, Germany) ESUs and then conducted a small clinical study. Methods Dedicated animal experimental models were created. To investigate the incision force, chicken meat was resected with a snare whose handle was a hung weight. To investigate the coagulation effect, a surgical needle electrode was inserted into a pig liver and energized, and to determine changes over time in the coagulation status, simulated EP was performed using a living pig. These experiments were performed using the knife-setting or snare-setting endoCUT modes and various effect, duration, and interval settings and compared with results for ICC (Erbe) ESUs. Based on the results, we performed EP in a small number of patients. Results The main factor affecting the incision force was duration. The coagulation effect was related to not only effect but also duration. In the endoCUT mode, knife-setting produced a higher incision force and lower coagulation effect. The nondischarge coagulation effect may cause deep ulceration. Based on the animal experiments, we concluded the ideal ESU setting for EP, “VIO EP mode,” is knife-setting with high duration, lowest effect, and low interval settings. In the clinical study, there were no significant adverse events such as bleeding, pancreatitis, or perforation. Conclusions “VIO EP mode” seems to afford optimal papillectomy. Larger scale clinical studies are needed to accumulate further data and make clinical comparisons with the ICC ESU.

Campylobacter jejuni is common cause of enteritis, but biliary infection rarely reported. An 82-year-old woman with pancreatic head cancer underwent endoscopic biliary drainage for malignant biliary obstruction. She was subsequently admitted for management of diarrhea. C. jejuni was identified in stool culture. Her symptoms resolved temporarily without antibiotics but flared up with a fever a few days later. She was diagnosed with acute cholangitis and bacteremia with C. jejuni. Endoscopic biliary drainage and antimicrobial administration improved her symptoms. As complications of C. jejuni diarrhea are rare, antibiotics are not necessarily indicated but sometimes are needed to prevent complications.

Background and Objectives: EUS-guided biliary drainage (EUS-BD) has recently been used for the treatment of not only malignant pancreaticobiliary diseases, but also for benign diseases. In most previous studies, EUS-BD was performed using a fully covered self-expandable metallic stent (SEMS), and data focusing on the usability of plastic stents for benign diseases are limited. We previously developed a plastic stent dedicated to EUS-guided hepaticoenterostomy (EUS-HES), and achieved favorable results in a feasibility study, although most of the patients had malignant diseases. Therefore, the aim of the present study was to evaluate the usability of dedicated plastic stents for EUS-HES in patients with benign pancreaticobiliary diseases. Patients and Methods: A total of 57 consecutive patients (28 men, median age: 68 years; range: 7–90 years) of normal and surgically altered anatomy with benign pancreaticobiliary diseases who underwent EUS-HES using the dedicated plastic stent between Jan. 2015 and Jun. 2020 were retrospectively analyzed. Results: The overall technical success rate of EUS-HES was 92.9% (53/57). Among the 4 cases of technical failure of plastic stent placement, a SEMS was placed in 1; percutaneous transhepatic biliary drainage was performed in 1; EUS-HES was reperformed 1 week later in 1; and observational management was selected in 1 patient. Adverse events associated with the procedure were seen in 15.7% (9/57) of the patients, namely, biliary peritonitis in 4, bleeding in 2, cholecystitis in 2, and pneumoperitoneum in 1 patient. Except for 1 patient who required blood transfusion owing to bleeding and 1 patient with cholecystitis who required percutaneous transhepatic gallbladder drainage, the other 7 patients were treated by conservative therapy. There were no intervention-associated deaths. Conclusion: Our results demonstrated that for patients with benign pancreaticobiliary diseases in whom conventional ERCP was unsuccessful, EUS-HES using a dedicated plastic stent was safe and feasible.

Background and Objectives: EUS-guided fine-needle biopsy (EUS-FNB) is considered a safe and useful method for preoperative diagnosis of resectable solid pancreatic masses. However, needle tract seeding (NTS) after EUS-FNB has recently been reported, which may affect long-term outcome. The aim of this study was to evaluate NTS after EUS-FNB. Materials and Methods: We reviewed 73 resected cases that underwent preoperative EUS-FNB for a pancreatic tumor from April 2014 to March 2016 and evaluated the utility and adverse events of EUS-FNB based on consecutively resected pathological specimens. Results: The final diagnoses were pancreatic ductal adenocarcinoma (n = 67), neuroendocrine neoplasm (n = 5), and acinar cell carcinoma (n = 1). The diagnostic accuracy of preoperative EUS-FNB was 98.6%. Clinical adverse events were observed in 4.1% of cases (bleeding, n = 2; acute pancreatitis, n = 1) and abnormal pathological findings in 4.1% (NTS, n = 2; acute focal pancreatitis, n = 1). Conclusions: Although EUS-FNB is useful for preoperative diagnosis of pancreatic tumors, we may need to reconsider the risk of NTS and use of EUS-FNB in patients with a resectable solid pancreatic mass unless the tract itself is planned to be resected.

Urgent or emergency endoscopic retrograde cholangiopancreatography (ERCP) is indicated for gallstone-induced acute cholangitis and pancreatitis. The technique and optimal timing of ERCP depend on the disease state, its severity, anatomy, patient background, and the institutional situation. Endoscopic transpapillary biliary drainage within 24 h is recommended for moderate to severe acute cholangitis. The clinical outcomes of biliary drainage with nasobiliary drainage tube placement and plastic stent placement are comparable, and the choice is made on a case-by-case basis considering the advantages and disadvantages of each. The addition of endoscopic sphincterotomy (EST) is basically not necessary when performing drainage alone, but single-session stone removal following EST is acceptable in mild to moderate cholangitis cases without antithrombotic therapy or coagulopathy. For gallstone pancreatitis, early ERCP/EST are recommended in cases with impacted gallstones in the papilla. In some cases of gallstone pancreatitis, a gallstone impacted in the papilla has already spontaneously passed into the duodenum, and early ERCP/EST lacks efficacy in such cases, with unfavorable findings of cholangitis or cholestasis. If it is difficult to diagnose the presence of gallstones impacted in the papilla on imaging, endoscopic ultrasonography can be useful in determining the indication for ERCP.

Background and Objectives: Several studies have demonstrated that EUS-guided fine-needle biopsy (EUS-FNB) is useful for diagnosing gastrointestinal subepithelial lesions (GI SELs). However, there is limited evidence regarding the use of Franseen needles during EUS-FNB for patients with GI SELs. In addition, the optimal approach for diagnosing small SELs is unclear. This study aimed to evaluate whether EUS-FNB using a Franseen needle was effective for diagnosing GI SELs, including small lesions. Methods: Between January 2013 and January 2020, 150 consecutive patients with GI SELs underwent EUS-FNA/FNB to achieve a histological diagnosis. Eighty-six consecutive patients who underwent EUS-FNB using a Franseen needle were compared to 64 patients who underwent EUS-FNA using a conventional needle. Results: The diagnostic yield was significantly higher using a Franseen needle than using a conventional needle (85% vs. 75%, P = 0.006). Furthermore, in cases with SELs that were 20 mm (adjusted odds ratio: 3.4, 95% confidence interval: 1.4–8.2; P = 0.006). Conclusion: Even when attempting to diagnose small GI SELs, EUS-FNB using a Franseen needle appears to provide a more efficient acquisition of true histological core tissue than using a conventional needle.

Although the lumen-apposing metal stent (LAMS) is useful for interventional endoscopic ultrasound (EUS) procedures, there has been some concern about the potential for stent-induced adverse events because of the high lumen-apposing force. A newly designed LAMS with less lumen-apposing force has been developed for use with a physician-controlled electrocautery-enhanced delivery system. The aim of this animal study was to evaluate the feasibility of performing interventional EUS using this newly designed LAMS system.Endoscopic ultrasound-guided cystogastrostomy was performed using the novel LAMS three times in a wet simulation model. EUS-guided gastroenterostomy and EUS-guided gallbladder drainage were then performed using the system in four pigs.The LAMS was successfully placed in all three EUS-guided cystogastrostomy procedures using the wet simulation model and in all four EUS-guided gastroenterostomy and gallbladder drainage procedures in the animal model. In the 3 weeks following the procedure, eating behavior was normal in all animals and there were no adverse events. The stents remained patent during this time and were removed without difficulty. The fistula was mature in all cases and a standard upper gastrointestinal endoscope was easily advanced via the fistula to observe the afferent and efferent loops or the lumen of the gallbladder. Necropsy confirmed complete adhesion between the stomach and the wall of the jejunum or gallbladder.Our study findings demonstrate the feasibility of this new LAMS system and its potential clinical value for interventional EUS.

High-intensity focused ultrasound (HIFU) is a novel advanced therapy for unresectable pancreatic cancer (PC). HIFU therapy with chemotherapy is being promoted as a novel method to control local advancement by tumor ablation. We evaluated the therapeutic effects of HIFU therapy in locally advanced and metastatic PC. PC patients were treated with HIFU as an optional local therapy and systemic chemotherapy. The FEP-BY02 (Yuande Bio-Medical Engineering) HIFU device was used under ultrasound guidance. Of 176 PC patients, 89 cases were Stage III and 87 were Stage IV. The rate of complete tumor ablation was 90.3%, while that of symptom relief was 63.8%. The effectiveness on the primary lesions were as follows: complete response (CR): n = 0, partial response (PR): n = 21, stable disease (SD): n = 105, and progressive disease (PD): n = 47, the primary disease control rate was 71.0%. Eight patients underwent surgery. The median survival time (MST) after diagnosis for HIFU with chemotherapy compared to chemotherapy alone (100 patients in our hospital) was 772.3 vs. 346.6 days (p &lt, 0.001). Compared with chemotherapy alone, the combination of HIFU therapy and chemotherapy demonstrated significant prolongation of prognosis. This study suggests that HIFU therapy has the potential to be a novel combination therapy for unresectable PC.

We report the viscoelastic relaxation mechanisms of cellulose nanocrystals (CNCs) dispersed individually in fluids. Linear viscoelasticity and flow birefringence of softwood and tunicate CNC/glycerol dispersions in the dilute regime were measured. The obtained results were then compared with molecular theories for the linear viscoelasticity of rigid rods and semiflexible rods at infinite dilution by taking length distributions of CNCs into account. Although CNCs are traditionally regarded as rigid Brownian rods, the viscoelastic relaxation was not explained solely by the rotational motions of rods. Alternatively, molecular theories for semiflexible rods well-described the viscoelastic behavior; the CNCs showed additional relaxation modes derived from microscopic internal motions including "tension" and "curvature", which originated from the finite flexural rigidity. Birefringence relaxation of the CNCs was dominated by the rotational motions of rods. Length distribution functions of the CNCs were thus calculated from the birefringence relaxation and agreed well with their microscopy-determined histograms.

Background and Aims Although balloon enteroscopy–assisted ERCP (BE-ERCP) is effective and safe for benign biliary diseases in patients with surgically altered anatomy (SAA), BE-ERCP is not always successful. Recently, EUS-guided antegrade intervention (EUS-AI) by using a 1-stage or 2-stage procedure has been developed for BE-ERCP failure cases. The aim of the present study was to evaluate the outcome of EUS-AI for benign biliary diseases in patients with SAA. Methods Of 48 patients in whom BE-ERCP failed, percutaneous transhepatic intervention was performed in 11. From November 2013 until November 2017, we retrospectively reviewed cases of an additional 37 patients with SAA who failed BE-ERCP and underwent EUS-AI for benign biliary diseases (common bile duct stones [n = 11], intrahepatic bile duct stones [n = 5], anastomotic strictures [n = 21]). Results The overall technical success of the creation of the hepatoenteric tract by EUS was 91.9% (34/37). Moderate adverse events were observed in 8.1% (biliary peritonitis [n = 3]). One-stage EUS-AI by EUS succeeded in 8 cases (100%) without any adverse events. In another 26 cases, 2-stage EUS-AI by ERCP was performed about 1 or 2 months later. Endoscopic antegrade therapy under fluoroscopy was successful in 6 cases. Per-oral cholangioscopy–assisted antegrade intervention was required in 19 cases (guidewire manipulation across the anastomotic stricture [n = 6], cholangioscopy-guided lithotripsy by using electrohydraulic lithotripsy [n = 13]). In 1 case, magnetic compression anastomosis was performed. The final clinical success rate of all EUS-AIs was 91.9%. Conclusions EUS-AI for benign biliary diseases in patients with SAA appears to be a feasible and safe alternative procedure after BE-ERCP failure.

Efficacy of cholangioscopy-assisted lithotripsy for difficult stones such as huge stones, multiple large stones and an impacted stone in patients with non-altered anatomy has been reported. Herein, we describe peroral direct digital cholangioscopy (PDCS)-assisted electrohydraulic lithotripsy (EHL) with a new technique in patients with surgically altered anatomy. Five patients received PDCS-assisted EHL with the monorail technique due to failed conventional stone extraction. Balloon enteroscope was removed, leaving the stiff guidewire in the bile duct and an overtube with inflated balloons. The cholangioscope was then inserted into the bile duct over the wire through the overtube. After direct visualization of the stone, PDCS-assisted EHL was carried out. This technique was named the 'monorail technique'. Complete removal of biliary stones in one session was accomplished in four patients and only one case required two sessions. There was no adverse event in any of the cases. PDCS-assisted EHL using the monorail technique was effective and safe for difficult biliary stones in patients with surgically altered anatomy.

Campylobacter jejuni is common cause of enteritis, but biliary infection rarely reported. An 82-year-old woman with pancreatic head cancer underwent endoscopic biliary drainage for malignant biliary obstruction. She was subsequently admitted for management of diarrhea. C. jejuni was identified in stool culture. Her symptoms resolved temporarily without antibiotics but flared up with a fever a few days later. She was diagnosed with acute cholangitis and bacteremia with C. jejuni. Endoscopic biliary drainage and antimicrobial administration improved her symptoms. As complications of C. jejuni diarrhea are rare, antibiotics are not necessarily indicated but sometimes are needed to prevent complications.

A 57-year-old woman presented with multilocular cysts like a bunch of grapes, 30mm in diameter, in the tail of the pancreas. The number of cysts has increased, and each one had grown. Eventually, they turned into a unilocular cyst with a cyst in the cyst structure of about 50mm in diameter. Laparoscopic distal pancreatectomy was performed, and the resected specimen was diagnosed with mucinous cystadenoma. We report the rare morphological change in this case and consider the mechanism of its occurrence based on pathological considerations.

Although Spy DS (SpyGlass DS Direct Visualization System) is considered to be useful for the diagnosis of bile duct strictures and the treatment of bile duct stones, there is limited data to date validating its efficacy. We hence retrospectively evaluated the clinical outcomes of the use of Spy DS in a large number of patients. A total of 183 patients who underwent Spy DS-guided procedures for indeterminate bile duct strictures (n = 93) and bile duct stones (n = 90) were analyzed retrospectively. All patients (93/93) with bile duct strictures successfully underwent visual observation, and 95.7% (89/93) of these patients successfully underwent direct biopsy. The sensitivity, specificity, and overall accuracy were 94.7%, 83.3%, and 90.3%, respectively, for visual impression, 80.9%, 100%, and 89.2%, respectively, for histopathological analysis of a direct biopsy, and 96.5%, 91.7%, and 94.6%, respectively, for visual impression combined with biopsy. Successful visualization of the stones was achieved in 98.9% (89/90) of the patients, and complete stone removal was achieved in 92.2% (83/90) of the patients, with an average of 3.3 procedures. The adverse events rate was 17.5% (32/183, cholangitis in 15 patients, fever the following day in 25, pancreatitis in 1, hemorrhage in 1, and gastrointestinal perforation in 1). No administration of antibiotics before the procedure was found to be a statistically significant risk factor for the development of fever after the procedure (p &lt, 0.01). Spy DS-guided procedures are effective for the diagnosis and treatment of bile duct lesions and can be performed with a low risk of serious adverse events.

Primary Sjogren’s syndrome (pSS) is a chronic progressive autoimmune disease with clinical phenotypic “Sicca symptoms”. In some cases, the diagnosis of pSS is delayed by 6–7 years due to the inefficient differential diagnosis of pSS and non-SS “Sicca”. This study aimed to investigate the difference between these two diseases, and in particular, their immunopathogenesis. Based on their gene expression profiles, we systematically defined for the first time the predicted disease-specific immune infiltration pattern of patients with pSS differentiated from normal donors and patients with non-SS “Sicca”. We found that it was characterized by the aberrant abundance and interaction of tissue-infiltrated immune cells, such as a notable shift in the subpopulation of six immune cells and the perturbed abundance of nine subpopulations, such as CD4+ memory, CD8+ T-cells and gamma delta T-cells. In addition, we identified essential genes, particularly long non-coding RNAs (lncRNAs), as the potential mechanisms linked to this predicted pattern reprogramming. Fourteen lncRNAs were identified as the potential regulators associated with the pSS-specific immune infiltration pattern in a synergistic manner, among which the CTA-250D10.23 lncRNA was highly relevant to chemokine signaling pathways. In conclusion, aberrant predicted disease-specific immune infiltration patterns and relevant genes revealed the immunopathogenesis of pSS and provided some clues for the immunotherapy by targeting specific immune cells and genes.

A woman in her 50s was referred due to a solid mass in the head of the pancreas. It was diagnosed as a neuroendocrine carcinoma (NEC) by endoscopic ultrasound-guided fine-needle aspiration. Consequently, pancreatoduodenectomy was performed. A well-differentiated adenocarcinoma component was revealed in the resected bile duct, suggesting a relationship with the NEC component in the pancreas. Genetic examination suggested that cholangiocarcinoma, but not coexisting carcinoma, was converted to NEC after the interstitial invasion. Finally, it was diagnosed as the NEC derived from the extrahepatic bile duct, which is rare at about 0.2-2% in gastrointestinal neuroendocrine neoplasms.

This study aimed to determine the clinicopathological features of the subtypes of ampullary carcinoma (AC) to explore the indications for endoscopic papillectomy (EP) in early AC. Fifty-seven patients with AC who underwent curative resection were retrospectively reviewed. The 0/IA stages were significantly more common in the intestinal type (I-type) than in the mixed and pancreatobiliary type (M&PB-type) (90.7% vs 35.7%, P P = 0.002). The tub1 rate was significantly higher in the I-type than in the M&PB-type (81.4% vs 35.7%, P = 0.001). In the I-type, the tub1 rate was significantly higher for Tis/T1a(ampulla) than for T1a tumors limited to the sphincter of Oddi (100% vs 42.9%, P = 0.004). These observations suggest that I-type AC with tub1 is an indication for EP. The concordance rate of pathological subtypes between endoscopic biopsy and resected specimens was high (κ = 0.8053, P

Extragalactic background light (EBL) consists of entire radiation emitted throughout the cosmic history and is one crucial observable quantity to study astrophysics in the early universe, such as first stellar objects or primordial black holes. In the visible and near-infrared, zodiacal light (ZL), sunlight scattered by interplanetary dust, is the brightest foreground for observer in the near-earth orbit and its uncertainty limits accuracy of the EBL measurement. To overcome this problem, observations from heliocentric distance beyond 5 au, where the ZL is negligible, is promising. To achieve the EBL observation in deep space, we have been developing EXo- Zodiacal Infrared Telescope (EXZIT) onboard a solar sail spacecraft to Jovian Trojans planned in Japan around 2030. According to our mission study, a three-mirror reflective telescope optics design with a 90mm × 50mm effective aperture and 16 deg × 8 deg field of view (FoV) followed by a focal plane array HAWAII-2RG with a linear variable filter makes available to detect the EBL at high significance in 0.4–1.6 μm with specific wavelength resolution of ∼ 20 . In the present study, we develop test optics to demonstrate optical performance in room temperature for the future observation. By adopting only mirrors of aspherical surface, we design the optics whose aberration is minimized to show point spread function (PSF) of approximately 3 pix × 3 pix on the focal plane. The mirrors are fabricated by machining aluminum alloy A6061 with a honeycomb processing on the back surface to reduce the mirror mass. After integrating and aligning the mirrors with support jigs, we measure the PSF on the focal plane by a visible camera by inserting collimated beam of different angle of incidence, covering the whole FoV. We evaluate the PSF size by analyzing encircled energy in comparison with that expected from the ray-trace simulation of the optics. Throughout the FoV of the optics, the measured PSF size is comparable to the simulation. The present study demonstrates the precision machining of the aspherical mirrors and the optical performance of the designed optics. As a next step, we plan to develop thermal structure of EXZIT to demonstrate the optical performance in low temperature.

We herein report three cases of patients with an ampullary neuroendocrine tumor (NET), who underwent endoscopic papillectomy (EP). No tumor recurrence or metastasis was detected in the patients for more than two years after EP. Generally, surgical resection is recommended for ampullary NETs by the European Neuroendocrine Tumor Society. However, as EP is less invasive than surgical resection, there are some reports of low-grade small ampullary NETs curatively treated by EP with long-term follow-up. We consider that EP may be a curative treatment for small and low-grade ampullary NETs without regional or distant metastasis.

Background/purpose The application of artificial intelligence to clinical diagnostics using deep learning has been developed in recent years. In this study, we developed an original computer-assisted diagnosis (CAD) system using deep learning analysis of EUS images (EUS-CAD), and assessed its ability to detect pancreatic ductal carcinoma (PDAC), using control images from patients with chronic pancreatitis (CP) and those with a normal pancreas (NP). Methods A total of 920 endosonographic images were used for the training and 10-fold cross-validation, and another 470 images were independently tested. The detection abilities in both the validation and test setting were assessed, and independent factors associated with misdetection were identified among participants' characteristics and endosonographic image features. Results Regarding the detection ability of EUS-CAD, the areas under the receiver operating characteristic curve were found to be 0.924 and 0.940 in the validation and test setting, respectively. In the analysis of misdetection, no factors were identified on univariate analysis in PDAC cases. On multivariate analysis of non-PDAC cases, only mass formation was associated with overdiagnosis of tumors. Conclusions Our pilot study demonstrated the efficacy of EUS-CAD for the detection of PDAC.

Background Peroral cholangioscopy (POCS) of indeterminate biliary strictures aims to achieve a diagnosis through visual examination and/or by obtaining targeted biopsies under direct visualization. In this large, prospective, multinational, real-life experience of POCS-guided evaluation of indeterminate biliary strictures, we evaluated the performance of POCS in this difficult-to-manage patient population. Methods This prospective registry enrolled patients, with indeterminate biliary strictures across 20 centers in Asia, the Middle East, and Africa. The primary end points were the ability to visualize the lesion, obtain histological sampling when intended, and an assessment of the diagnostic accuracy of POCS for malignant strictures. Patients were followed for 6 months after POCS or until a definitive malignant diagnosis was made, whichever occurred first. Results 289 patients underwent 290 POCS procedures with intent to biopsy in 182 cases. The stricture/filling defect was successfully visualized in 286/290 (98.6 %), providing a visual diagnostic impression in 253/290 (87.2 %) and obtaining adequate biopsies in 169/182 (92.9 %). Procedure-related adverse events occurred in 5/289 patients (1.7 %). POCS influenced patient management principally by elucidating filling defects or the causes of bile duct stricture or dilation. The visual impression of malignancy showed 86.7 % sensitivity, 71.2 % specificity, 65.8 % positive and 89.4 % negative predictive value, and 77.2 % overall accuracy compared with final diagnosis. Histological POCS-guided samples showed 75.3 % sensitivity, 100 % specificity, 100 % positive and 77.1 % negative predictive value, and 86.5 % overall accuracy. Conclusion In this large, real-life, prospective series, POCS was demonstrated to be an effective and safe intervention guiding the management of patients with indeterminate biliary strictures.

Objective Endoscopic papillectomy (EP) has been recognized to be a safe and reliable treatment modality for ampullary adenomas. The purpose of this study was to determine the safety and efficacy of endoscopic piecemeal resection for laterally spreading ampullary adenomas and to compare these findings with a control population of smaller conventional ampullary tumors treated in the same time period. Methods Between May 1999 and September 2015, 136 patients underwent EP at Tokyo Medical University hospital. A total of 125 patients underwent en bloc resection, and 11 patients underwent piecemeal resection. Results The final pathological diagnoses were 103 adenomas, 14 carcinomas in adenomas, 4 carcinomas, and 4 hyperplasia in the en bloc resection group, versus 7 adenomas, 3 carcinomas in adenoma, and 1 carcinomas in the piecemeal resection group. A single treatment session was possible in 104 (83.2%) of the 125 patients in the en bloc resection group and in 8 (72.7%) of the 11 in the piecemeal resection group. The total resection rate including additional treatments was 98.4% in the en bloc resection group and 100% in the piecemeal resection group. Conclusion Piecemeal resection for laterally spreading ampullary adenomas was sufficiently performed compared with en bloc resection.

The dynamic viscoelasticity and birefringence of well-characterized semiflexible polymer solutions—cellulose tris(phenyl carbamate)/tricresyl phosphate solutions—were investigated over a wide concentration region ranging from a dilute to a tightly entangled regime where the entanglement spacing is smaller than the Kuhn segment size. The stress optical rule did not hold true in the tightly entangled regime, indicating that the molecular origin of stress is not simply attributed to the orientation of segments but to the bending of chains, which does not contribute to birefringence significantly. At high frequencies, the power law behavior with the exponent 3/4 due to the tension stress was observed for the complex shear moduli at all the concentrations.

BACKGROUND AND AIMS Endoscopic ultrasound (EUS)-guided transmural drainage using a covered biflanged metal stent (CBFMS) and a conventional tubular biliary covered self-expandable metal stent (CSEMS) has recently been performed by EUS experts. However, appropriate traction force of the sheath to prevent the migration during stent deployment is well unknown. Herein, we assessed the anchoring force (AF) of the distal flange in CBFMSs and CSEMSs. METHODS The AFs of four CBFMSs (Stents AX, NG, PL, and SX) and six CSEMSs (Stents BF, BP, EG, HN, SP, and WF) were compared in an ex vivo setting. We assessed the AF produced by each stent using an EUS-guided transmural drainage model and an EUS-guided hepaticogastrostomy model consisting of sheet-shaped specimens of the stomach, gelatin gel, and gelatin tubes. RESULTS For CBFMSs, the maximum AF of Stent AX was significantly higher than those of Stents PL and SX (P

BACKGROUND AND AIM Several experts of direct peroral videocholangioscopy (D-PVCS) using a conventional ultraslim endoscope have reported its usefulness for the diagnosis and therapy of biliary tract diseases. We have additionally developed a dedicated double-bending D-PVCS technique for freehand scope insertion. In this study, we developed an ex vivo training model for the freehand double-bending D-PVCS technique and compared it with the technique using a conventional ultraslim endoscope. METHODS The ex vivo model was made for training using a U-shape insertion pattern. A third prototype endoscope and an ultraslim upper gastrointestinal endoscope were used. Two experts and nine non-experts performed D-PVCS using the freehand technique. RESULTS The two experts could not advance the tip of the endoscope to the hilar portion using the freehand technique, but they could achieve technical successful insertion to the hilar portion with the third prototype cholangioscope using the freehand technique alone. The non-experts could not advance the tip of the endoscope to the bile duct using the freehand technique. On the other hand, two (22.2%) non-experts could advance the tip of the third prototype cholangioscope using the freehand technique before the training conducted by the experts. After the training, all the non-experts could advance the tip of the third prototype cholangioscope to the hilar portion. CONCLUSIONS The novel ex vivo model using a third prototype cholangioscope was useful for training in the use of the freehand D-PVCS technique.

Aqueous nanocellulose dispersions were prepared from wood cellulose by 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-mediated oxidation. The obtained TEMPO-oxidized cellulose was converted into TEMPO-oxidized cellulose nanofibrils (TOCNs) of different lengths by controlling the nanofibrillation conditions in water or using dilute acid hydrolysis. The average lengths and length distributions of TOCNs have been measured from transmission electron microscopy (TEM) and atomic force microscopy (AFM) images. However, because the number of nanocelluloses observable in TEM and AFM images is limited, a more reliable method is needed to obtain the lengths/length distributions of TOCNs. In this study, the aqueous TOCN dispersions were subjected to a combination of field-flow fractionation (FFF) and multi-angle laser-light scattering (MALLS). The optimum FFF operation conditions for the acid-hydrolyzed TOCN were first established to obtain reasonable data. For TOCNs with average lengths > 400 nm, suitable separation could not be achieved using the FFF/MALLS system. In contrast, the TOCNs with average lengths of 170 and 270 nm were adequately separated according to their sizes by the FFF system. The TOCN length distribution patterns corresponded well to those obtained from TEM images. However, the amounts of TOCNs with lengths > 250 nm were underestimated compared with those determined from TEM images. For TOCNs with average lengths of 170 and 270 nm, the molar mass at each TOCN length was determined using the FFF/MALLS system combined with a refractive index detector, where a specific refractive index increment of 0.165 mL/g was used for TOCN.

Inclusion compounds (ICs) have the potential to act as drug carriers. In this study, an IC consisting of acetaminophen incorporated into 2,4,6-tris(4-chlorophenoxy)-1,3,5-triazine (CLPOT) was synthesized ([CLPOT-acetaminophen]). Elemental analysis, 1H NMR spectroscopy and thermogravimetry-differential thermal analysis (TG-DTA), of the IC confirmed that ~0.1 acetaminophen molecules were included as guest molecules per CLPOT unit cell. The inclusion of acetaminophen in the 1D nanochannels of CLPOT was further confirmed by the DTA results of [CLPOT-acetaminophen], which showed the endothermal peak at 157 °C indicating the desorption of acetaminophen confined in the CLPOT nanochannels. These results suggest that CLPOT could be used as a stable microscopic carrier of biomaterials.

AIM To evaluate the feasibility and reliability of endoscopic transpapillary bile duct biopsy for the diagnosis of biliary strictures. METHODS A total of 360 patients (241 men) who underwent endoscopic retrograde cholangiopancreatography for biliary strictures with biopsy from April 2012 to March 2016 at Tokyo Medical University Hospital were retrospectively reviewed. This study was approved by our Institutional Review Board (No. 3516). Informed consent was obtained from all individual participants included in this study. The biopsy specimens were obtained using a novel slim biopsy forceps (Radial Jaw 4P, Boston Scientific, Boston, MA, United States). RESULTS The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 69.6%, 100%, 100%, 59.1%, and 78.8%, respectively. The sensitivity was 75.6% in bile duct cancer, 64% in pancreatic cancer, 61.1% in gallbladder cancer, and 57.1% in metastasis. In bile duct cancer, a lower sensitivity was observed for perihilar bile duct stricture (68.7%) than for distal bile duct stricture (83.1%). In terms of the stricture lengths of pancreatic cancer, gallbladder cancer, and metastasis, a longer stenosis resulted in a better sensitivity. In particular, there was a significant difference between pancreatic cancer and gallbladder cancer (P < 0.05). One major complication was perforation of the extrahepatic bile duct with bile leakage. CONCLUSION Endoscopic transpapillary biopsy alone using novel slim biopsy forceps is feasible and reliable, but restrictive. Biopsy should be performed in consideration of the stricture level, stricture length, and cancer type.

Background and Aims EUS-guided transluminal drainage (EUS-TD) and sequential direct endoscopic necrosectomy (DEN) for pancreatic fluid collections (PFCs) by using a dedicated biflanged metal stent (BFMS) has been reported as a useful alternative to using plastic stents or a conventional metal stent. However, current dedicated BFMSs have limitations. Recently, a new BFMS with solidly constructed biflanges and various stent lengths matched to the PFC condition has been developed. Herein, we prospectively evaluated this new BFMS for the treatment of PFCs. Methods From July 2015 to July 2016, EUS-TD by using the new BFMS was performed in 12 patients for PFCs (4 patients with pancreatic pseudocysts, 8 patients with walled-off necrosis). When clinical resolution could not be achieved, DEN was performed the following day. Results The stent was deployed successfully with a median procedure time of 16 minutes (range 11-24 minutes) and with no procedure-related adverse events in any patients (12/12, 100%). DEN via the stent was achieved in all patients in whom they were attempted (4/4,100%). Spontaneous stent migration or stent dislocation during DEN was not observed in any patients. Two WON patients died from spontaneous pseudoaneurysm rupture and multiple organ failure. The PFCs in the other 10 patients completely resolved, and later the stent was removed with no difficulty in 9 patients after a median time of 48 days (range 30-180 days). Conclusions The new BFMS is technically feasible and safe for the treatment of PFCs. (Clinical trial registration number: UMIN000021347.)

Six types of CNCs with different sizes were prepared from tunicins by sulfuric acid hydrolysis and subsequent sonication in water. The size distributions of CNCs were comprehensively evaluated by turbidimetry, small angle X-ray scattering, and microscopy to predict their intrinsic viscosities. Experimental intrinsic viscosities [η] of the CNC dispersions were evaluated by shear viscosity measurement, and then compared with their theoretical [η] values based on theories for rotational motions of rigid rods. The experimental [η] values for the straight CNCs were in good agreement with their theoretical [η] values, irrespective of the size and distributions. On the other hand, the experimental [η] value of the kinked CNC was higher than the theoretical [η] value, in agreement with a theoretical calculation giving higher intrinsic viscosities for bent fibers.

Highlight This experimental study using a plastic globe and fine-needle aspiration needle demonstrated that distention of the jejunum is the most important point to avoid mispuncture and misdeployment of devices in endoscopic ultrasonography-guided gastrojejunostomy. Itoi and colleagues recommend the double-balloon occlusion method to endosonographers for safe and reliable endoscopic ultrasonography-guided gastrojejunostomy.

Objective Endoscopic papillectomy is increasingly being used for ampullary adenoma treatment. However, it remains challenging despite increased safety with treatment advances. The ideal power output and electrosurgical current mode for mucosal resection are not established. We aimed to identify the ideal electrical pulse for use during resection. Methods This pilot randomized, single-blind, prospective, multicenter trial, recruited patients with ampullary adenomas and conventional anatomy who were scheduled to undergo endoscopic papillectomy. Endoscopic treatment was performed using a standardized algorithm and patients were randomized for endoscopic papillectomy with Endocut or Autocut. The primary outcome was the incidence of delayed bleeding. Incidence of procedure-related pancreatitis, successful complete resection, pathological findings, and other adverse events were secondary endpoints. Results Sixty patients were enrolled over a 2-year period. The incidences of delayed bleeding (13.3% vs. 16.7%, P = 1.00) and pancreatitis (27% vs. 30%, P = 0.77) were similar between both groups. The rate of crush artifacts was higher in the Endocut than in the Autocut group (27% vs. 3.3%, P = 0.03). Immediate bleeding when resecting tumors greater than 14 mm in diameter was more common in the Autocut than in the Endocut group (88% vs. 46%, P = 0.04). Conclusions The Autocut and Endocut modes have similar efficacy and safety for endoscopic papillectomy. The Endocut mode may prevent immediate bleeding in cases with large tumor sizes, although it causes more frequent crush artifacts. Registry and the registration number The Japanese UMIN Clinical Trials Registry (UMIN-CTR: 000021382).

Background and Objectives: EUS-guided biliary drainage (EUS-BD) has been reported as an effective alternative drainage technique. However, clinical data on EUS-BD for patients with acute cholangitis (AC) are limited. The aim of this study was to analyze the clinical outcomes of EUS-BD in patients with AC. Patients and Methods: Nineteen patients with AC who underwent urgent or early drainage (within 96 h) by EUS-guided hepaticoenterostomy (EUS-HES) between January 2014 and November 2019 were retrospectively reviewed. Furthermore, the clinical outcomes of EUS-HES using a plastic stent in the AC group (n = 15) were compared to those in the non-AC group (n = 88). Results: In the 19 AC cases, the technical and clinical success rate was 100% with 5.3% of moderate adverse events (biliary peritonitis [n = 1]). Regarding the comparison between the AC group and the non-AC group, the clinical success rate was 100% in both groups and the adverse event rate was not statistically significantly different (P = 0.88). Although the recurrent biliary obstruction (RBO) rate was not statistically significantly different (P = 0.43), the early RBO rate was statistically significantly higher in the AC group (26.7% vs. 3.4%, P < 0.001). Kaplan–Meier curves showed that AC was associated with a shorter time to RBO (P = 0.046). The presence of AC was found to be an independent risk factor of early RBO (odds ratio = 10.3; P = 0.005). Conclusions: Urgent or early biliary drainage (within 96 h) by EUS-BD can be a feasible and safe alternative procedure for patients with AC, although there is a tendency of early RBO.

Background and Aims There are currently no prospective, controlled trials of needle puncture speed in EUS-guided FNA (EUS-FNA). In this study, we prospectively evaluated the accuracy of histological diagnosis and the tissue acquisition rate of EUS-FNA by using the door-knocking method (DKM) with a standard 22-gauge needle. Methods From November 2013 to August 2014, 82 patients who had solid pancreatic masses underwent EUS-FNA in which the conventional method (CM) and DKM with 2 respective passes in turn were used. The primary outcomes of this study were the accuracy of histological diagnosis and the rates of tissue acquisition in 2 FNA procedures by using these 2 methods. Results Although the successful tissue acquisition rate for histology was not significantly different with the DKM and CM (91.5% vs 89.0%, P = .37), the high cellularity tissue acquisition rate for histology with the DKM was significantly superior to that with the CM (54.9% vs 41.5%, P = .03). However, adequate quality rate and accuracy were not different in the DKM and CM (78.0% vs 80.5%, P = .42 and 76.8% vs 78.0%, P = .50, respectively). In the transgastric puncture group, although the adequate quality rate and accuracy were similar in the DKM and CM (84.1% vs 79.4%, P = .30 and 84.1% vs 76.2%, P = .11, respectively), the tissue acquisition rate tended to be higher with the DKM than the CM (93.7% vs 85.7%, P = .06). Moreover, the high cellularity tissue acquisition rate was significantly better with the DKM than the CM (63.5% vs 39.7%, P = .002). On the other hand, in the transduodenal puncture group, although the tissue acquisition rate was similar with the DKM and CM (84.2% vs 100%, P = .13), the adequate quality rate and accuracy were significantly lower with the DKM than with the CM (57.9% vs 84.2%, P = .03 and 52.6% vs 84.2%, P = .02, respectively). Conclusion EUS-FNA by using a 22-gauge needle with the DKM did not improve the accuracy of histological diagnosis, but enabled acquisition of a larger amount of tissue specimen by using transgastric puncture. (Trial Registration: http://www.umin.ac.jp/english/: UMIN000012127.)

Softwood and hardwood bleached kraft pulps (SBKP and HBKP, respectively) and highly crystalline native celluloses such as algal, tunicate, bacterial and cotton lint celluloses were dissolved in 8 % (w/v) LiCl/N,N-dimethylacetamide (DMAc) after ethylenediamine (EDA) pretreatment. Complete dissolution of SBKP and other highly crystalline native celluloses in 8 % LiCl/DMAc was achieved after solvent exchange from EDA to DMAc through methanol. Neutral sugar composition analysis showed no significant differences between the original and EDA-treated pulps. A combination of size-exclusion chromatography and multi-angle laser light scattering (SEC–MALLS) was used to analyze the cellulose solutions after dilution to 1 % (w/v) LiCl/DMAc. The 0.05 % (w/v) solutions of highly crystalline cellulose in 1 % (w/v) LiCl/DMAc contained entangled molecules, and therefore 0.025 % (w/v) cellulose solutions in 1 % (w/v) LiCl/DMAc were used in the SEC–MALLS analysis to obtain reliable conformation plots (or double-logarithmic plots of molecular mass vs. root-mean-square radius). All the cellulose samples except SBKP gave conformation plots with slope values of 0.56–0.57, showing that these cellulose molecules had random-coil conformations. In contrast, SBKP gave a slope value of 0.35, indicating that some branched structures were present in the high-molecular-mass fraction. Double-logarithmic plots of the reduced viscosities of the cellulose solutions in 1 % (w/v) LiCl/DMAc versus the molecular mass were linear, except for SBKP, also suggesting the presence of anomalous cellulose structures in SBKP.

Background Recently, a new digital cholangiopancreatoscopy (DCPS) has been developed. The aim of this study is to retrospectively evaluate the utility of new DCPS in patients with pancreaticobiliary diseases. Methods Digital cholangiopancreatoscopy was used in 26 patients (16 men) with pancreaticobiliary diseases that could not be diagnosed and treated by standard endoscopic retrograde cholangiopancreatography (ERCP). The procedures included DCPS-guided tissue sampling and interventions. Technical success and adverse events were evaluated. Results Among the 26 patients, 19 patients were classified for diagnostic purposes and seven for therapeutic purposes. The detailed breakdown of the particular conditions and numbers of patients was as follows: indeterminate bile duct (BD) lesion, indeterminate pancreatic duct (PD) lesion, lithotripsy by yttrium aluminum garnet-laser or electrohydraulic lithotripsy, removal of migrated BD stent and PD stent, and guidewire passing across the biliary stricture. The overall technical success rates of visualizing the target lesions and therapeutic interventions were 100% and 85.7%, respectively. The incidence of procedure-related adverse events among the patients was 7.7% (2/26). Cholangitis developed in one of the patients and post-endoscopic sphincterotomy bleeding in one patient. All adverse events were successfully treated by conservative therapy. Conclusion Digital cholangiopancreatoscopy has a high potential for providing an accurate diagnosis and facilitating therapy in patients with pancreaticobiliary diseases.

We report the viscoelastic properties of core-shell-structured, hemicellulose-rich nanofibrillated cellulose (NFC) in dispersion and wet-film states. The hemicellulose-rich NFC (hemicellulose neutral sugars 23%, carboxylate 0.2 mmol g(-1)), prepared from Japanese persimmons, had a core crystallite thickness of 2.3 nm and unit fibril thickness of 4.2 nm. A carboxylate-rich NFC (hemicellulose neutral sugars 7%, carboxylate 0.9 mmol g(-1)) with crystallite and fibril widths of 2.5 and 3.3 nm, respectively, was used as a reference. The solid-concentration dependencies of the storage moduli of gel-like water dispersions of the hemicellulose-rich NFC were weaker than those of carboxylate-rich NFC, and the dispersions were loosely flocculated even at high salt concentrations and low pH values. The viscoelastic properties of wet NFC films were similar to those of their dispersions; the hemicellulose-rich NFC films were significantly less sensitive to salt concentration and pH and were soft and swollen at high salt concentrations and low pH values.