Partial Stent-in-Stent Method with an Uncovered Self-Expandable Metallic Stent for Unresectable Malignant Hilar Bile Duct Obstruction.

(1) Background: There is controversy regarding stent placement for unresectable malignant hilar biliary obstruction (UMHBO). We mainly use the partial stent-in-stent (PSIS) method with an uncovered self-expandable metallic stent (UCSEMS) based on the drainage area and patency period. In this study, we investigated the usefulness and safety of the PSIS method. (2) Methods: In total, 59 patients who underwent the PSIS method for UMHBO at our hospital were included in the study. The technical success rate, clinical success rate, time to recurrent biliary obstruction (TRBO) and overall survival (OS) from the first placement, factors affecting TRBO and OS, and early complications within 30 days after the procedure were evaluated retrospectively. (3) Results: The technical and clinical success rates were 100% and 96.6%, respectively, with a TRBO of 121 days [95% confidence interval: 82-231] and an OS of 194 days [95% confidence interval: 113-305] after the first placement. Early complications occurred in nine patients (15.3%), including five cases of cholangitis, three cases of pancreatitis, and one case of cholecystitis. (4) Conclusions: The PSIS method for UMHBO is safe and useful with high technical and clinical success rates.

Pancreatic Juice Cytology Evaluations Using Synthetic Secretin and Serial Pancreatic Juice Aspiration Cytological Examination for the Diagnosis of Pancreatic Ductal Adenocarcinoma.

Pathological examination by endoscopic ultrasound-fine needle aspiration is not possible in approximately 10% of pancreatic tumor cases. Pancreatic juice cytology (PJC) is considered an alternative diagnostic method. However, its diagnostic capability is insufficient, and PJC has been repeatedly redevised. Serial pancreatic juice aspiration cytological examination (SPACE) and secretin-loaded PJC (S-PJC) have been recently introduced as alternative diagnostic methods. This study aimed to determine the diagnostic capacity and safety of SPACE and S-PJC using a propensity score-matched analysis. The sensitivity, specificity, and accuracy were 75.0%, 100%, and 92.3% for S-PJC, respectively, and 71.4%, 100%, and 92.3% for SPACE, respectively, meaning that there was no significant difference between the groups. Four patients (15.4%) each in the S-PJC and SPACE groups experienced complications, including postendoscopic retrograde cholangiopancreatography, pancreatitis, and cholangitis. Overall, there was no difference in efficacy and safety between the SPACE and S-PJC groups.

Comparison between Target Sample Check Illuminator and White Light Observation in Discriminating the Presence of Target Specimen for Endoscopic Ultrasound-Guided Fine Needle Aspiration Sample.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an essential endoscopic tissue sampling method for diagnosing pancreatobiliary diseases; however, determining the presence of target specimens mixed in the blood by conventional observation is challenging due to the small size of the obtained sample. This study investigated the usefulness of a target sample check illuminator (TSCI) that emits a specific wavelength of light to determine the presence of target specimens. Twenty-seven patients who underwent EUS-FNA at our hospital were included. Conventional white light observation was performed for the collected samples, followed by TSCI; six people evaluated the presence of the target specimen on a 5-point scale. The target specimen discrimination score using TSCI (median: 5) was significantly higher than that using conventional white light observation (median: 1) (p < 0.001). No significant difference was observed in the discrimination score between the evaluator (novice vs. expert, p = 0.162) and puncture needle (22G vs. 25G, p = 0.196). The discriminability of TSCI in the samples obtained using EUS-FNA was significantly higher than that of conventional observation. TSCI does not depend on the evaluator or puncture needle for the identification of the target specimen; hence, it can provide a good pathological specimen and may contribute to the improvement of the diagnostic ability.

The Effectiveness of the Multiple-Attending-Physicians System Compared With the Single Attending-Physician System in Inpatient Setting: A Mixed-Method Study.

OBJECTIVES: Medical facilities have been required to effectively utilize insufficient human resources in many countries. Therefore, we qualitatively and quantitively compared physicians' working burden, and assessed advantages and disadvantages of the single- and the multiple-attending physicians systems in inpatient care. METHODS: In this cross-sectional study, we extracted electronic health record of patients from a hospital in Japan from April 2017 to October 2018 to compare anonymous statistical data between the single-attending and multiple-attending-physicians system. Then, we conducted a questionnaire survey for all physicians of single and multiple-attending systems, asking about their physical and psychiatric workload, and their reasons and comments on their working styles. RESULTS: The average length of hospital stay was significantly shorter in the multiple-attending system than in the single-attending system, while patients' age, gender, and diagnoses were similar. From the questionnaire survey, no significant difference was found in all categories although physical burden in multiple-attending system tended to be lower than that in single-attending system. Advantages of multiple-attending system extracted from qualitative analysis are (1) improvement of physicians' quality of life (QOL), (2) lifelong-learning effect, and (3) improving the quality of medical care, while disadvantages were (1) risk of miscommunications, (2) conflicting treatment policies among physicians, and (3) patients' concern. CONCLUSIONS: The multiple-attending physician system in the inpatient setting can reduce the average length of stay for patients and also reduce the physical burden on physicians without compromising their clinical performance.

Large Gallstones Stacked Together in the Common Bile Duct after Choledochojejunostomy.

A 65-year-old man had a history of cholecystectomy and treatment for cholelithiasis with a common bile duct incision. Owing to frequent cholangitis, he underwent choledochojejunostomy. Twenty years after the surgery, he was hospitalized for cholangitis and was suspected of having hilar cholangiocarcinoma based on imaging findings. Percutaneous transhepatic cholangioscopy using a SpyGlass™ DS (Boston Scientific, Marlborough, USA) showed gallstones and bile sludge in the bile ducts, but no tumors were noted. Electrohydraulic shockwave lithotripsy with double-balloon enteroscopy enabled complete stone removal; a direct visual biopsy with peroral cholangioscopy showed no malignancy in the bile duct.

Efficacy and Safety of Pancreatic Juice Cytology with Synthetic Secretin in Diagnosing Malignant Intraductal Papillary Mucinous Neoplasms of the Pancreas.

The risk of malignant transformation of intraductal papillary mucinous neoplasm (IPMN) is presently assessed using imaging, which remains unsatisfactory. Given the high viscosity of pancreatic juice, pancreatic juice cytology (PJC) is considered an investigational procedure. We previously demonstrated that the diagnostic performance of PJC was improved via synthetic secretin loading in pancreatic ductal carcinoma. This study aimed to evaluate the efficacy of synthetic secretin-loaded PJC (S-PJC) for IPMN. The usefulness and safety of S-PJC were prospectively evaluated in 133 patients with IPMN. Overall, 92, 12, and 26 patients had branch duct, main duct, and mixed-type lesions, respectively. The risk classifications based on the 2017 international consensus guidelines were high-risk stigmata, worrisome features, and no risk in 29, 59, and 45 patients, respectively. Synthetic secretin loading improved the sensitivity of PJC from 50.0% to 70.8%. Complications included 13 (9.8%) cases of mild pancreatitis, 1 (0.8%) case of acute cholangitis, and 1 (0.8%) case of Mallory-Weiss syndrome, all of which resolved with conservative treatment. In conclusion, synthetic secretin-loaded PJC improved the diagnostic performance of cytology for malignant IPMN. We recommend using synthetic secretin-loaded PJC for the preoperative pathological diagnosis of malignant IPMN in clinical settings.

The Usefulness of Peroral Cholangioscopy for Intrahepatic Stones.

Peroral cholangioscopy (POCS) is believed to be effective in treating intrahepatic stones; however, reports on its efficacy are few. We reviewed the results of intrahepatic stones treated with fluoroscopic guidance or POCS. This study included 26 patients who underwent endoscopic treatment for intrahepatic stones at our institution between January 2017 and December 2021. We retrospectively evaluated the procedure time and adverse events in the first session and the rate of complete stone removal. Complete stone removal was achieved in 92% (24/26); POCS was required in 16 of 26 (62%) procedures and the complete stone removal was achieved in 15 of 16 (94%) of these procedures. The POCS group had a significantly longer procedure time than the fluoroscopy group. Cholangitis incidence was high; however, no difference was noted between patients with and without POCS, and all cases were mild and treated conservatively. Endoscopic treatment for intrahepatic stones may lead to an increase in the incidence of cholangitis, requires specialized devices such as a cholangioscope, and should be performed in an established institution by experienced staff. POCS is useful for intrahepatic stones formed upstream of the stenosis and intrahepatic stones piled in the bile duct.

Evaluation of error sources in a gravimetric technique for preparation of a reference gas mixture (carbon dioxide in synthetic air).

One method of preparing a primary reference gas mixture is the gravimetric blending method. Uncertainty of a few mg in mass measurements is unavoidable when preparing reference gas mixtures under current laboratory conditions with our facilities, equipment, and materials. There are many sources of errors when using this method. In this study, several sources of errors were re-evaluated for our process for preparation of carbon dioxide in synthetic air. As a consequence of the re-evaluation, it was found that some sources of errors had significant effects on gravimetric concentrations of the gas mixtures. These sources are: (1) different masses of the reference cylinder and sample cylinder (an error in the readings of the electronic mass comparator), (2) leakage of the inner gas from valves of the cylinders, and (3) cooling of the gas cylinder caused by filling with high-pressure liquefied carbon dioxide gas. When the mass measurements were performed under uncontrolled conditions, the errors due to sources (1), (2), and (3) were as high as 20 mg, 24 mg, and 13 mg, respectively. In this paper, the detailed results from re-evaluation of these sources of errors are discussed.

Development of an Analytical System Based on a Magneto-pneumatic Oxygen Analyzer for Atmospheric Oxygen Determination.

A high-precision analytical system to observe the variations in the amount fractions of atmospheric oxygen with a very small uncertainty was developed. The system comprises a magneto-pneumatic oxygen analyzer and three automatic pressure controllers. The drift of the analyzer's signal intensity can be reduced when the amount fractions of oxygen in the sample and reference gases are similar because the temperature coefficient of the analyzer linearly depends on the difference between these amount fractions. The repeatability of oxygen determination and the long-term stability of the system were tested to assess the applicability of the analyzer to field-based measurements for continuous atmospheric observations. The standard deviation of the average for 10-min measurements in the 5-day long-term stability test was 0.7 µmol mol-1 after a temperature correction. This indicates that the system can continuously measure the amount fractions of oxygen in the atmosphere for a few days without interruption for any calibration and/or compensation for the signal drift.

Application and Validation of a Determination Method Using Post-column Reaction Gas Chromatography of Nitrogen-containing Organic Compounds.

In this work, we applied post-column reaction gas chromatography (GC) using a flame ionization detector (FID) system to study nitrogen-containing organic compounds (NOCs). The results were subsequently validated. After separation by column, the target components were converted to carbon dioxide using an oxidizing catalyst and then reduced to methane, followed by detection using an FID. SI-traceable testing mixtures containing NOCs (isoprocarb, napropamide, and pendimethalin) were prepared by the gravimetric blending method. These mixtures were analyzed using a post-column reaction GC-FID system; standard materials of hydrocarbons were used as calibrants in this analysis. The determined values were compared with the values obtained for samples prepared at the corresponding concentrations, and statistical analyses were performed in all cases. It was shown that the determined and prepared values agreed well with each other within the uncertainty limits.

Development of an ultra-micro sample injector for gas chromatography using an ink-jet microchip.

An ultra-micro sample injector for gas chromatography (GC) was developed. An ink-jet microchip, originally used for industrial recorder, was modified at the edge near to an orifice, and fixed into the GC. In order to evaluate the characteristics of this injector, a sample injector and a thermal conductive detector (TCD) were connected directly, while water was used as the test sample. The volume of the droplet, the interval time and the back-pressure to the ink-jet microchip were investigated. Within the range of 1 - 5 nL volume injected sample, the TCD response according to the amount of the sample volume (the volume of one droplet from the ink-jet microchip was about 1 nL) was obtained. A good reproducibility of the peak area was obtained to be about 1.0% of the RSD value. In order to compare the injection method of the ink-jet chip with that using a micro-syringe, the method using the ink-jet chip could introduce 1/1000 of the amount of the sample and gave reproducible results.

Low-temperature Electronic Paramagnetic Resonance Measurements of TEMPO and 4-Hydroxy-TEMPO Benzoate for Purity Analyses by the Effective Magnetic-moment Method.

The purities of two high-purity organic compounds with a nitroxyl radical moiety were quantified based on their free-radical content using the effective magnetic-moment method. Magnetic moments were measured and X-band electron paramagnetic resonance (EPR) spectra were obtained using a superconducting quantum interference device and X-band EPR spectrometer, respectively, over a wide temperature range of near-room temperature to near-liquid-helium temperature. Concerning measurements of effective g-values using an EPR spectrometer, both the sweep direction and sweep speed were taken into account to obtain accurate g-values. The purities of 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) and 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl benzoate (4-hydroxy-TEMPO benzoate) were close to 1 kg kg-1 with relative uncertainties of 1%, which represented improved values compared to those obtained by us previously. These results show a possibility for both compounds to act as reference materials in providing reliable quantification of free radicals per unit mass using this analytical method.

Spatial resolution improvement of scanning microscopy based on thermal lens spectroscopy with a total-internal-reflection arrangement.

In scanning microscopy by total internal reflection with thermal lens spectroscopy, its spatial resolution depends on the distance between the sample and a converging lens, which corresponds to the objective lens in an ordinary optical microscope. It was found that the resolution was best when the signal induced by the thermal lens effect was maximum. The distance was precisely adjusted by monitoring the signal intensity, and the resolution became twice better than that previously reported. Using a shorter focal-length lens, a resolution of 1.9 microm was attained.

Development of a scanning microscopy by total internal reflection coupled with thermal lens spectroscopy.

Non-destructive measurement of a small region on a solid/liquid interface is of great importance in physical chemistry and biochemistry, especially in the research of thin films and cell membranes. Optical methods for surface analysis with high lateral resolution are suitable methods for monitoring them. We now report a new scanning optical microscopic method to which total internal reflection coupled with a thermal lens technique was introduced. Its lateral resolution was estimated both experimentally and theoretically. To experimentally estimate the resolution, the grid patterns of thin photoresist films with well-defined lateral structures were measured. The experimental resolution was about 45 microm, which was almost same as the diameter of the excitation beam at a glass/sample interface. From this result, it was verified that this new scanning microscopy ideally worked.

High-precision GC-TCD for verification of gravimetrically prepared primary gas standards of in nitrogen.

Gravimetric preparation method is one of the most precise and accurate methods for preparing primary standard gas mixtures (PSMs). Although the principle and execution of the gravimetric method are not complicated, the uncertainty of the gravimetric method is so small that a seemingly minor error can result in an incorrect amount fraction of the PSM. Therefore, verifying the amount fraction of the PSMs is a necessary step. We perform a high-precision comparison between the PSMs of oxygen in nitrogen (∼100 µmol per mol) using a well-stabilized gas chromatograph with a thermal conductivity detector (GC-TCD) system in conjunction with high-precision pressure monitoring for sample amount correction and a quality-control cylinder technique in which the PSMs were analyzed against a reference cylinder, which leads to the cancellation of the drift in the sensitivity of the GC-TCD. After optimization of the measurement conditions, the relative expanded uncertainty reaches 0.022% (coverage factor k = 2), which is equivalent to the uncertainty of the PSMs. The Consultative Committee for Amount of Substance of the Comité International des Poids et Mesures performed a key comparison CCQM-K53, in which one of the PSMs used in this work was compared and agreed well with PSMs prepared by other National Metrology Institutes. These results show that the GC-TCD system developed in this work is sufficiently reliable, precise and accurate to verify PSMs.

A flow-based enzyme-linked immunosorbent assay on a polydimethylsiloxane microchip for the rapid determination of immunoglobulin A.

A flow-based enzyme-linked immunosorbent assay (ELISA) on a polydimethylsiloxane (PDMS) microchip has been developed for the rapid determination of immunoglobulin A (IgA). The analytical principle of this integrated method is the same as the conventional sandwich-type ELISA. A primary antibody (anti-IgA) was adsorbed on the surface of a PDMS microchannel, and then an antigen (IgA) and a secondary antibody (anti-IgA HRP labeled) were reacted successively. The resulting antigen-antibody complex, fixed on the surface of the microchannel, was detected using Amplex((R)) Red and a fluorescent imaging system. The calibration curve of the IgA standard solution was linear in the range of 0-50ng/mL at the flow rate of 10muL/min. This flow rate corresponds to the reaction time of 4.8s. Compared to the conventional assay on a 96-well microtiter plate, the present assay on the microchip dramatically shortened the reaction time necessary for the enzyme-substrate reaction from 30min to 4.8s, i.e., to 1/375. The amounts of the reagent and sample were also reduced to 1/100 compared to the 96-well microtiter plate.

An integrated microfluidic device in polyester for electrophoretic analysis of amino acids.

A precolumn reaction chamber was integrated into a polyester microfluidic device with a miniaturized detection system. The reaction chamber was designed to be a zigzag channel, 70 microm in width, 8 mm in length, followed by a wider straight channel, 150 microm in width, 2 mm in length. The detection system is composed of an embedded light-emitting diode (LED), an integrated optical fiber, and a photomultiplier tube (PMT). A success in amino acid analysis using the integrated microchemical analysis device proved that the precolumn reaction chamber was compatible with the integrated detection system. Three kinds of amino acids, arginine, glycine, and phenylalanine, mixed and reacted with 7-fluoro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-F) in the precolumn reaction chamber to produce fluorescent products, were separated by micellar eletrokinetic chromatography (MEKC) and detected by LED-excited fluorescence. The detection limits for arginine, glycine, and phenylalanine were 1, 1, and 0.5 mM, respectively, which can be improved by further optimizations of the reaction system and detection system.

Fabrication of an integrated PDMS microchip incorporating an LED-induced fluorescence device.

A microfluidic device with an integrated fluorescence detection system has been developed in order to miniaturize the entire analytical system. A blue or green light-emitting diode (LED) and an optical fiber were mounted in a polydimethylsiloxane-based microchip. The performance of this device was evaluated by microchip electrophoresis. When a green LED was used as the light source, the calibration curve of Sulforhodamine-101 was linear over the range 1-100 microM. The detection limit was found to be 600 nM (240 amol) for a S/N ratio of 3. When using a blue LED, the calibration curve of Fluorescein was linear over the range 0.2-100 microM. The detection limit was estimated to be 120 nM (50 amol) (S/N=3). The detection sensitivity per unit power was comparable to that of LIF. The RSD values for the migration time, peak height and peak area were 0.74, 7.18 and 9.45%, respectively. The integrated microfluidic device was successfully used to determine amino acid derivatives.

Evaluation of lateral resolution of scanning surface microscopy by total internal reflection with thermal lens effect.

We have developed a novel method for in situ and non-destructive surface analyses, or a total internal reflection with thermal lens spectroscopy (TIR-TLS), which has sufficient sensitivity to monitor phenomena in thin films, such as lipid bilayers. In this study, we applied TIR-TLS to microscopy for surface analyses, and we experimentally obtained its lateral resolution using the edge of a chromium film made by a photolithography technique. The obtained resolution was 20 microm, which was 60% of the diameter of an excitation beam at the interface. The estimated resolution with a simple model agreed with the experimental one, and from this model, TIR-TLS microscopy has the same resolution as that of ordinary optical microscopy. The microscopy by TIR-TLS was applied to a sample whose contrast was too weak to be visually seen, and an image of the sample was obtained without any loss of resolution.