Prognostic nutritional index after introduction of atezolizumab with bevacizumab predicts prognosis in advanced hepatocellular carcinoma: A multicenter study.

INTRODUCTION: Atezolizumab plus bevacizumab (Atez/Bev) is the preferred treatment for advanced hepatocellular carcinoma (HCC). However, biomarkers of therapeutic efficacy have remained unclear. We took a retrospective approach to explore the role of prognostic nutritional index (PNI) for predicting the outcomes of Atez/Bev treatment. METHODS: One hundred twenty-five HCC patients were enlisted; these patients received Atez/Bev treatment and underwent dynamic computerized tomography/magnetic resonance imaging to determine the treatment response on at least one occasion between October 2020 and January 2023, and their PNI before treatment and at the beginning of the second cycle (PNI-2c) was evaluated. RESULTS: During the initial evaluation, 2 (2%), 28 (22%), 70 (56%), and 25 (20%) patients exhibited a complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), respectively. Patients with non-PD tended to have higher PNI at baseline and PNI-2c than those with PD (p = 0.245 and 0.122, respectively), with optimal baseline PNI and PNI-2c cut-off values of 42.6 and 40.4, respectively. PNI at baseline could not be used to predict overall survival (OS) or progression-free survival (PFS). However, PNI-2c predicted OS and PFS (PNI-2c ≥ 40.4 vs. < 40.4: 25.3 vs. 16.2 months, P = 0.008 for OS; 12.7 vs. 8.4 months, P = 0.036 for PFS). A multivariate analysis showed a significant association between PNI-2c and OS. CONCLUSIONS: PNI-2c is a predictor of prognosis in HCC patients treated with Atez/Bev therapy.

Injectable testosterone PLGA microsphere with different characteristics: effect of preparation method (paddle mixing versus microfluidic device).

The purpose of this study was to compare the characteristics of testosterone polylactic-co-glycolic (PLGA) microspheres prepared by a paddle mixer or microfluidics device. The comparison was conducted by not only in vitro evaluation but also in vivo evaluation which has not been reported up to date. We discovered that, among the steps in microsphere preparation, the solvent removal process strongly impacted drug content, particle size and surface morphology. Spectroscopic measurements suggested that molecular interactions and crystallinity of the drug incorporated in the microspheres differed. For the drug release profile, although both mixer- and microfluidics-prepared samples showed similar sustained release of the incorporated drug for approximately one month in vitro, they exhibited different plasma concentration profiles in vivo. Together, our findings show that the preparation process, especially the solvent removal process, may affect the physicochemical characteristics of testosterone PLGA microspheres, leading to different in vivo performance.

Polymer Characteristics for Drug Layering on Particles Using a Novel Melt Granulation Technology, MALCORE®.

MALCORE®, a novel manufacturing technology for drug-containing particles (DCPs), relies on the melt granulation method to produce spherical particles with high drug content. The crucial aspect of particle preparation through MALCORE® involves utilizing polymers that dissolve in the melt component, thereby enhancing viscosity upon heating. However, only aminoalkyl methacrylate copolymer E (AMCE) has been previously utilized. Therefore, this study aims to discover other polymers and comprehend the essential properties these polymers need to possess. The results showed that polyvinylpyrrolidone (PVP) was soluble in the stearic acid (SA) melt component. FTIR examination revealed no interaction between SA and polymer. The phase diagram was used to analyze the state of the SA and polymer mixture during heating. It revealed the mixing ratio and temperature range where the mixture remained in a liquid state. The viscosity of the mixture depended on the quantity and molecular weight of the polymer dissolved in SA. Furthermore, the DCPs prepared using PVP via MALCORE® exhibited similar pharmaceutical properties to those prepared with AMCE. In conclusion, understanding the properties required for polymers in the melt granulation process of MALCORE® allows for the optimization of manufacturing conditions, such as temperature and mixing ratios, for efficient and consistent drug layering.

Dual role of autotaxin as novel biomarker and therapeutic target in pancreatic neuroendocrine neoplasms.

Pancreatic neuroendocrine neoplasms (panNENs) are rare pancreatic neoplasms, and descriptions of treatment remain limited. Autotaxin (ATX) is a secreted autocrine motility factor involved in the production of lysophosphatidic acid (LPA), a lipid mediator that promotes the progression of various cancers. The aim of this study was to clarify the importance of the ATX-LPA axis in panNENs and to confirm its contribution to panNEN progression using clinical data, cell lines, and a mouse model. Serum ATX level was higher in patients with panNEN than in patients with other pancreatic diseases (chronic pancreatitis, pancreatic ductal adenocarcinoma [PDAC], intraductal papillary mucinous neoplasm, autoimmune pancreatitis) and healthy controls, and 61% of clinical specimens stained strongly for ATX. In a case we encountered, serum ATX level fluctuated with disease progression. An in vitro study showed higher ATX mRNA expression in panNEN cell lines than in PDAC cell lines. Cell proliferation and migration in panNEN cell lines were stimulated via the ATX-LPA axis and suppressed by RNA interference or inhibitors. An in vivo study showed that intraperitoneal injection of GLPG1690, an ATX inhibitor, suppressed tumor progression in a xenograft model. These findings revealed that ATX expression is significantly elevated in panNEN and is related to the progression of panNEN. We showed the potential of ATX as a novel biomarker and therapeutic target.

Clinical impact of bile-derived exosomal microRNAs as novel diagnostic and prognostic biomarkers for biliary tract cancers.

Sampling of bile juice during endoscopic retrograde cholangiopancreatography (ERCP) has potential benefit of being amenable to the identification of novel biomarkers in liquid biopsy. This study reports the results of a global investigation of exosomal microRNAs (miRNAs) in bile to identify potential biomarkers for biliary tract cancers (BTCs). Eighty-eight bile samples collected during ERCP (45 BTC and 43 noncancer control samples) were enrolled in this study. Eleven BTC samples and nine control samples were assigned as the discovery set. Exosomes in bile and serum samples were collected using a glass membrane column with size-controlled macroporous glass (MPG), and exosomal miRNA expression profiles were evaluated using comprehensive miRNA microarray analysis (3D-Gene). For validation, exosomal miRNA in the bile samples of 34 BTCs and 34 controls were comprehensively evaluated using 3D-Gene. In the discovery set, eight exosomal miRNAs in bile were identified as significant aberrant expression markers, while no miRNA with aberrant expression in serum was identified. In a comparison of the discovery and validation sets, miR-451a and miR-3619-3p were identified as reproducible upregulated markers, and the combination of the two bile miRNAs showed an excellent area under the curve (0.819) value for diagnosing BTCs. In addition, high miR-3619-3p expression in bile reflects poorer prognosis of BTCs (hazard ratio = 2.89). The MPG-extracted exosomal miRNAs in bile aspirated during ERCP provide a convenient new approach for diagnosing biliary diseases. Bile-derived miRNA analysis with miR-451a and miR-3619-3p represents a potentially valuable diagnostic strategy for identifying BTCs as well as a predictive indicator of BTC prognosis.

Drug Extended-Release System Utilizing Micelle Formation of Highly Water-Soluble Drugs and a Counter Polymer.

The objective of this study is to clarify the mechanism of extending release of highly water-soluble drugs via counter polymer (CP) utilization in poly(ethylene oxide) (PEO)/polyethylene glycol (PEG) matrix tablets. Carbomer, poly(acrylic acid), was used as a CP, which has the opposite charges to the drugs. The in vitro release of several highly water-soluble drugs from PEO/PEG tablet with or without CP were tested, the relationship between the sustained release effect by a CP (SRE) and the physicochemical properties of the drugs was investigated. The results demonstrated that the utilization of CP can extend the release of some highly water-soluble drugs by effectively controlling the drug diffusion through matrices. On the other hand, the effectiveness of CP was different depending on the drugs applied. There were not statistical correlations between SRE and physicochemical properties such as solubility, molecular weight, and charge intensity of the drugs, while a micelle forming property of the drugs played an important role in SRE by CP. It was concluded that CP, Carbomer, having negative charges could effectively interact with opposite charges on the surface of stable drug micelles, which could result in a significant decrease in drug diffusion leading to extended drug release. It is considered that the system utilizing CP is a promising approach to achieve extended release of highly water-soluble drugs with a reasonable tablet size, especially in the case of large drug loading.

The neutrophil-to-lymphocyte ratio at the start of the second course during atezolizumab plus bevacizumab therapy predicts therapeutic efficacy in patients with advanced hepatocellular carcinoma: A multicenter analysis.

AIM: Atezolizumab plus bevacizumab (Atez/Bev) therapy is expected to have good therapeutic efficacy for patients with advanced hepatocellular carcinoma (HCC). However, the clinical indicators that predict therapeutic efficacy have not been established. We retrospectively investigated whether the neutrophil-to-lymphocyte ratio (NLR) during Atez/Bev therapy could predict therapeutic efficacy. METHOD: In total, 110 patients with HCC were enrolled; they were treated with Atez/Bev therapy and evaluated for their initial response by dynamic CT or MRI at least once between October 2020 and July 2022. RESULTS: Of the 110 patients with HCC at the initial evaluation, two (2%) showed a complete response (CR), 22 (20%) partial response (PR), 62 (56%) stable disease (SD), and 24 (21%) progressive disease (PD). The NLR at the start of the second course (NLR-2c) increased from CR + PR to SD to PD. There was no significant association between the baseline NLR and the initial therapeutic response. Patients with CR + PR had lower NLR-2c values than those with SD + PD (p < 0.001) and the optimal cut-off value of NLR-2c was 1.97. Patients with NLR-2c <1.97 had better overall survival and progression-free survival (PFS) than those with NLR-2c ≥1.97 (p = 0.005 for overall survival; p < 0.001 for PFS). A multivariate analysis showed that female sex, higher PIVKA-II levels at baseline, and higher values of NLR-2c were significantly associated with poorer PFS. CONCLUSIONS: The NLR-2c value predicts the initial therapeutic response and prognosis of patients with HCC treated with Atez/Bev therapy.

Sangelose-based gels and films: effects of glycerol and α-cyclodextrin and their pharmaceutical application.

OBJECTIVE: To evaluate the possible application of Sangelose as an alternative to gelatin and carrageenan for the development of film substrates, and to examine the effect of glycerol and α-cyclodextrin (α-CyD) on the viscoelastic properties of Sangelose-based gels and the physical properties of the films. SIGNIFICANCE: Sangelose-based gels/films can serve as a potential viable alternative to gelatin and carrageenan in pharmaceutical applications. METHODS: Glycerol (a plasticizer) and α-CyD (a functional additive) were added to Sangelose, and gels and films were prepared. The gels were evaluated by dynamic viscoelasticity measurements, and the films were evaluated by scanning electron microscopy, Fourier-transform infrared spectroscopy, tensile tests, and contact angle measurements. Soft capsules were prepared using the formulated gels. RESULTS: The strength of the gels was affected when only glycerol was added to Sangelose and α-CyD addition resulted in rigid gels. However, the addition of α-CyD with 10% glycerol weakened the gels. Tensile tests suggested that glycerol addition affected the formability and malleability of the films, while α-CyD addition affected their formability and elongation properties. The addition of 10% glycerol and α-CyD did not affect the flexibility of the films, suggesting that the malleability and strength were impacted. Soft capsules could not be prepared by adding only glycerol or α-CyD to Sangelose. Soft capsules with favorable disintegration behavior were obtained upon adding α-CyD to gels along with 10% glycerol. CONCLUSIONS: Sangelose combined with a suitable amount of glycerol and α-CyD has preferable characteristics for film formation and may have potential applications in the pharmaceutical and health food sectors.

Drug delivery to the intestinal lymph by oral formulations.

Oral drug delivery systems (DDS) targeting lymphocytes in intestinal lymphatic vessels, ducts, and nodes are useful for treating diverse diseases. The intestinal lymph harbors numerous lymphocyte subsets, and DDS containing lipids such as triglycerides and fatty acids can deliver drugs to the lymph through the chylomicron pathway. DDS are efficient, thus allowing the administration of reduced drug doses, which mitigate systemic adverse effects. Here we review orally administered lipid formulations comprising oil solutions, suspensions, micro/nanoemulsions, self-micro/nano emulsifying DDS, liposomes, micelles, solid lipid nanoparticles, and nanostructured lipid carriers for targeting drugs to the lymph. We first describe the structures of lymphatic vessels and lymph nodes and the oral absorption of lipids and drugs into the intestinal lymph. We next summarize the effects of the properties and amounts of lipids and drugs delivered into the lymph and lymphocytes, as well as their effects on drug delivery ratios of lymph to blood. Finally, we describe lymphatic DDS containing saquinavir, tacrolimus, and methotrexate, and their potency that reduces drug concentrations in blood, which are associated with systemic adverse effects.

Impact of Properties of Hydrated Silicon Dioxide as Core Material on the Characteristics of Drug-containing Particles Prepared by the 2-step Process Melt Granulation Technology, MALCORE®.

Drug-containing particles (DCPs) are frequently used as cores in the development of solid oral dosage forms. The wet layering technique, which is a typical approach for preparing DCPs, requires the use of solvents and a long manufacturing time. In our previous study, we developed a novel manufacturing technology, MALCORE®, which can solve these problems through melt granulation. However, particle size control methods for DCPs in MALCORE® and the effect of the physical properties of the hydrated silicon dioxide (HSD) used for the core have not been clarified. The aim of this study was to examine the effects of the particle and pore sizes of HSD on the properties of the prepared DCPs. The results showed that the DCPs prepared using MALCORE® could be controlled by the particle size of HSD. The drug-loading efficiency tended to decrease as HSD particle size increased. Additionally, the amount of drug layering in DCPs increased as the pore size of HSD increased, but HSDs with a pore size much larger than the particle size were not able to properly layer the drug. These findings are helpful for applying MALCORE® to a variety of oral drug formulations.

A New Approach for Characterizing the Thixotropic Properties of Gel Formulations as Sprayable Agents Based on Rheological Analysis.

The present study evaluated the rheological properties of gel formulations composed of the thixotropic peptide amphiphile, palmitoyl-glycine-histidine (Pal-GH), and the thickener, propylene glycol alginate (PGA), to propose a proper approach to design sprayable gel formulations with good spray performance and high retention of a therapeutic agent. The hysteresis loop area (HLA), a conventional index of thixotropy, was determined from the relationship between the shear stress and shear rate of various formulations with different amounts of Pal-GH and PGA. In addition, a new assessment method for characterizing the thixotropy using the initial structure recovery speed was determined based on the time course of the complex modulus (G*) after structural breakdown of the gel formulations. The G* values increased with the increase in the amount of Pal-GH and PGA, indicating that the formulations were not deformable. Additionally, high HLA and high initial structure recovery speed are preferable when selecting a formulation with good spray performance and high retention. As suitable combinations of Pal-GH and PGA could exhibit both high HLA and high initial structure recovery speed, they are promising components for gel formulations to be used as sprayable agents with good spray performance and high retention. The results also suggested that the initial structure recovery speed would reflect the thixotropy for the formulation more appropriately than HLA. Thus, the initial structure recovery speed could be a useful scale for the preparation of sprayable gel formulations.

One-step versus two-step distal self-expandable metal stent placement: A multicenter prospective randomized trial.

BACKGROUND AND AIM: Two methods of transpapillary covered self-expandable metal stent (SEMS) placement are used for distal malignant biliary obstruction (MBO): after initial drainage by plastic stent (two-step method) and without previous drainage (one-step method). METHODS: In total, 90 patients with unresectable pancreatic cancer and distal MBO were enrolled in this prospective multicenter randomized study and allocated to one-step (n = 45) and two-step (n = 45) groups. The main outcome was the time to recurrent biliary obstruction (TRBO). Secondary outcomes were the rates of early and late adverse events, survival time, the time required for bilirubin level reduction, and cost-effectiveness. RESULTS: The median TRBO did not differ significantly between the one-step and two-step groups (not available vs 314 days, P = 0.134). SEMS migration occurred significantly more frequently in the two-step group (14.3% vs 0%, P = 0.026). No significant difference was observed between groups in early (7.3% vs 14.3%, P = 0.483) or late (12.2% and 11.9%, P = 1) adverse events other than RBO, survival time (P = 0.104), or the median number of days required to reach a bilirubin level considered to be acceptable for chemotherapy administration (<3 mg/dL; P = 0.881). The total costs of stent placement and reintervention were significantly lower in the one-step SEMS group (3347 vs 5465 US dollars, P < 0.001). CONCLUSIONS: The superiority of TRBO with two-step SEMS placement was not demonstrated. One-step SEMS placement might be a promising method from the viewpoints of cost-effectiveness and less invasiveness (UMIN-CTR clinical trial registration number: UMIN000016010).

Design of novel tacrolimus formulations with chemically synthesized oils for oral lymphatic delivery.

High consumption of oil formulations has been reported to reduce the blood exposure of drugs like tacrolimus. Consumption of oil formulations has also been shown to inhibit T-cell production of interleukin-2 (IL-2) compared to solid dispersion formulations (SDFs). However, a large amount of oil causes gastrointestinal side effects such as diarrhea and low compliance. Here, we investigated the feasibility of reducing the amount of oil and substitution of chemically synthetized oils for natural oils in these formulations. Reducing the amount of sunflower oil increased blood tacrolimus exposure despite sufficient suppression of IL-2 production. While medium-chain triglyceride (MCT) increased tacrolimus blood exposure, addition of 10% glyceryl monostearate (GMS) to MCT significantly decreased drug blood exposure without requiring a large amount of oil (p < .05). Effects of the contents of GMS in the MCT/GMS formulations, and fatty acid composition in GMS on drug blood exposure were also investigated. The results indicated that both the amount and type of oil were important for maintaining a good balance between a reduction in blood exposure and sufficient IL-2 suppression. The ratio of drug concentration in lymphocytes to that in whole blood after dosing with an oil formulation was significantly higher than that after administration of the SDF (p < .01). These results indicate the feasibility of developing oral oil tacrolimus formulations to reduce systemic side effects and maintain high efficacy for practical use in patients.

Fabrication of Zero-Order Sustained-Release Floating Tablets via Fused Depositing Modeling 3D Printer.

A three-dimensional (3D) printer is a powerful tool that can be used to enhance personalized medicine. A fused deposition modeling (FDM) 3D printer can fabricate 3D objects with different internal structures that provides the opportunity to introduce one or more specific functionalities. In this study, zero-order sustained-release floating tablet was fabricated using FDM 3D printer. Filaments comprising poorly water-soluble weak base drug, itraconazole (ITZ) and polymers (hydroxypropyl cellulose and polyvinylpyrrolidone) were prepared, and tablets with a hollow structure and different outside shell thicknesses were fabricated. In the 3D printed tablets, ITZ existed as an amorphous state and its solubility improved markedly. As the outside shell thickness of the tablet increased, drug release was delayed and floating time was prolonged. In the tablets with 0.5 mm of the upper and bottom layer thickness and 1.5 mm of the side layer thickness, holes were not formed in the tablets during the dissolution test, and the tablets floated for a long period (540 min) and showed nearly zero-order drug release for 720 min. These findings may be useful for improving the bioavailability of several drugs by effective absorption from the upper small intestine, with floating gastric retention system.

Crystal Structures of Flavone C-Glycosides from Oolong Tea Leaves: Chafuroside A Dihydrate and Chafuroside B Monohydrate.

Chafuroside A and chafuroside B are flavone C-glycosides isolated from oolong tea leaves. They have a number of beneficial pharmacological activities related to antiinflammation at various concentrations. However, no crystallographic study of chafurosides has yet been reported. In the present study, the crystal structures of chafuroside A and chafuroside B were investigated using single-crystal X-ray diffraction. The asymmetric unit of the chafuroside A crystal consists of one chafuroside A and two water molecules, and that of chafuroside B contains one chafuroside B and one water molecule. The flavone moiety of chafuroside A is curved, i.e., the angle between the best-fit planes of the chromene and phenyl rings is 18.9°, whereas the chafuroside B flavone moiety is relatively flat. A comparison of the curvatures of the flavone moieties of various C-glycosides showed that the curvature of chafuroside A is significantly larger than those of the others. This structural feature might contribute to the differences between the strengths of the pharmacological activities of chafurosides A and B.

Novel Dissolution Approach for Tacrolimus-Loaded Microspheres Using a Dialysis Membrane for in Vitro-in Vivo Correlation.

The aim of this study was to establish a novel approach to in vitro dissolution evaluation using a combination of the paddle method and a dialysis membrane, both to predict the overall in vivo performance of tacrolimus microspheres and also to identify a suitable dissolution test method to describe the in vivo initial burst phenomenon. This new dissolution method for evaluating the release of tacrolimus from microspheres consisted of rotating a customized paddle inside a dialysis membrane using a conventional paddle apparatus. Findings were compared with a method in which the paddle was rotated outside the dialysis membrane, the conventional paddle method, and the flow-through cell method. We concluded that the paddle method with a dialysis membrane and internal agitation, which was designed to mimic in vivo conditions, predicted the overall pharmacokinetic (PK) profile of tacrolimus microspheres whereas the conventional paddle method described the initial burst. These findings suggest that it may not be possible to predict both the PK profile and initial burst using a single analysis method. We therefore recommend that evaluation of the initial burst be performed separately. In conclusion, we propose that combination of the paddle method with a dialysis membrane and internal agitation to evaluate the overall PK profile, together with the paddle method to describe the in vivo initial burst, represents a novel approach to in vitro dissolution evaluation for microsphere formulations.

Covered duodenal self-expandable metal stents prolong biliary stent patency in double stenting: The largest series of bilioduodenal obstruction.

BACKGROUND AND AIM: Endoscopic biliary and duodenal stenting (DS; double stenting) is widely accepted as a palliation therapy for malignant bilioduodenal obstruction. The aim of the current study was to investigate the patency and adverse events of duodenal and biliary stents in patients with DS. METHODS: Patients who underwent DS from April 2004 to March 2017 were analyzed retrospectively with regard to clinical outcomes and predictive factors of recurrent biliary and duodenal obstruction (recurrent biliary obstruction [RBO] and recurrent duodenal obstruction [RDO]). RESULTS: A total of 109 consecutive patients was enrolled. Technical success of DS was achieved in 108 patients (99.1%). Symptoms due to biliary and duodenal obstruction were improved in 89 patients (81.7%). RBO occurred in 25 patients (22.9%) and RDO in 13 (11.9%). The median times to RBO and RDO from DS were 87 and 76 days, respectively. Placement of a duodenal uncovered self-expandable metal stent (U-SEMS) was significantly associated with RBO in the multivariable analysis (P = 0.007). Time to RBO was significantly longer in the duodenal covered self-expandable metal stent group than in the U-SEMS group (P = 0.003). No predictive factors of RDO were detected, and duodenal stent type was not associated with the time to RDO (P = 0.724). CONCLUSIONS: Double stenting was safe and effective for malignant bilioduodenal obstruction. Duodenal U-SEMS is a risk factor for RBO. The covered self-expandable metal stent is the preferred type of duodenal SEMS in patients with DS (Clinical trial registration number: UMIN000027606).

Novel Orally Disintegrating Tablets Produced Using a High-Pressure Carbon Dioxides Process.

It is well known that high-pressure carbon dioxide (CO2) lowers the glass transition temperature (Tg) of polymers. We therefore investigated whether Tg depression of high-pressure CO2 results in interparticle bridging of a polymer and the tablet characteristics that makes the manufacture of an orally disintegrating tablet (ODT) possible. Copolyvidone (Kollidon®) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) were examined and found to exhibit a large Tg depression. Placebo ODTs were prepared and hardness, disintegration rate, porosity, and change in thickness and appearance were evaluated before and after the high-pressure CO2 treatment. This enabled the establishment of the optimal conditions for pressure, temperature, and treatment time under pressure. Experimental results showed that it was possible to manufacture ODTs comprising Kollidon® as a water-soluble polymer with CO2 treatment under the suitable conditions such as temperature at 45°C, pressure lower than 8 MPa, and a treatment time shorter than 30 min, which is a new ODT manufacturing process called "Carbon Dioxide Assisted Tablet Formation Scheme" (CATS). In comparison to the conventional processes, which require high temperatures or humidity, CATS is expected to be applicable to drugs that are unstable at high temperature and humidity, and to functional drug particles used for bitter taste masking, sustained release, and other uses.

Novel characteristics of traction force in biliary self-expandable metallic stents.

BACKGROUND AND AIM: In recent years, knowledge concerning the mechanical properties of self-expandable metallic stents (SEMS) has increased. In a previous study, we defined traction force and traction momentum and reported that these characteristics are important for optimal stent deployment. However, traction force and traction momentum were represented as relative values and were not evaluated in various conditions. The purpose of the present study was to measure traction force in various situations assumed during SEMS placement. METHODS: Traction force and traction momentum were measured in non-stricture, stricture, and angled stricture models using in-house equipment. RESULTS: Stricture and angled stricture models had significantly higher traction force and traction momentum than those of the non-stricture model (stricture vs non-stricture: traction force, 7.2 N vs 1.4 N, P < 0.001; traction momentum, 237.8 Ns vs 62.3 Ns, P = 0.001; angled stricture vs non-stricture: traction force, 7.4 N vs 1.4 N, P < 0.001; traction momentum, 307.2 Ns vs 62.3 Ns, P < 0.001). Traction force was variable during SEMS placement and was categorized into five different stages, which were similar in both the stricture and angled stricture models. CONCLUSIONS: We measured traction force and traction momentum under simulated clinical conditions and demonstrated that strictures and the angular positioning of the stent influenced the traction force. Clinicians should be aware of the transition of the traction force and should schedule X-ray imaging during SEMS placement.

Endoscopic retrograde cholangiopancreatography-related adverse events in patients with type 1 autoimmune pancreatitis.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is frequently performed for the diagnosis and treatment of type 1 autoimmune pancreatitis (AIP). However, the prevalence of ERCP-related adverse events in patients with type 1 AIP has not been evaluated. We aimed to clarify the feasibility of ERCP in patients with type 1 AIP. METHODS: We retrospectively reviewed 82 consecutive ERCP procedures performed in patients with type 1 AIP from 2004 to 2014 in one university hospital and three tertiary-care referral centers. One hundred four ERCP procedures in chronic pancreatitis and 1123 in non-AIP cohort were enrolled as control groups. We compared the incidence of post-ERCP pancreatitis (PEP) between type 1 AIP and control groups. We evaluated the incidence of ERCP-related adverse events and various predictive factors for hyperamylasemia after ERCP. RESULTS: Pancreatography and cholangiography by ERCP were obtained in 78 (95.1%) and 76 (92.7%) patients, respectively. The incidence of PEP, cholangitis, and bleeding was 1.2% (1/82), 0%, and 1.2%, respectively. PEP occurred in type 1 AIP patient with diffuse parenchymal imaging, and the severity was mild. The incidences of PEP were 2.9% (3/104) and 5.4% (61/1123) in chronic pancreatitis and normal cohort, respectively. The incidence of PEP was slightly lower in type 1 AIP than non-AIP cohort (1.2% vs 5.8%, p = 0.119). There were no significant predictive factors for hyperamylasemia after ERCP in type 1 AIP. CONCLUSIONS: The incidence of ERCP-related adverse events is low in patients with type 1 AIP. ERCP-related procedures are feasible in the diagnosis and treatment of AIP.