Feasibility and safety of EUS-guided biliary drainage in inexperienced centers: a multicenter study in southwest Japan.

BACKGROUND AND AIMS: EUS-guided biliary drainage (EUS-BD) has shown promising procedural outcomes in high-volume centers. Although inferior procedural outcomes were reported in inexperienced centers during the early days of EUS-BD, the current outcomes are unknown. This study aimed to clarify the feasibility and safety of EUS-BD in centers that recently introduced EUS-BD. METHODS: This multicenter retrospective study was conducted at 22 centers that introduced EUS-BD between 2017 and 2022. A maximum of 20 initial EUS-BD cases at each center were evaluated. The clinical outcomes and experience of 84 endoscopists who performed these procedures were examined. Primary outcomes were the rate of technical success and adverse events (AEs), whereas secondary outcomes were risk factors associated with technical failure and procedure-related AEs. RESULTS: Two hundred fifty-five patients were enrolled. The technical success rate was 91.4% (233/255). Among 22 technical failure cases, guidewire manipulation failure was the most common cause (n = 12) followed by tract dilation failure (n = 5). The AE rate was 10.2% (26/255). Multivariate analysis identified a puncture target diameter of <5 mm (odds ratio, 3.719; 95% CI, 1.415-9.776; P = .008) and moderate ascites extending to the liver surface (odds ratio, 3.25; 95% CI, 1.195-8.653; P = .021) as independent risk factors for technical failure and procedure-related AEs, respectively. Endoscopists' procedural experience was not a risk factor for technical failure or procedure-related AEs. CONCLUSIONS: The feasibility and safety of EUS-BD were maintained during the induction phase at inexperienced centers. These data will be helpful to better understand the current status of EUS-BD. (Clinical trial registration number: UMIN 000053615.).

Radial force and wire structure determine the onset of covered self-expandable metal stent migration in endoscopic ultrasound-guided hepaticogastrostomy: Measurement of sliding-resistance force using a porcine model.

BACKGROUND: Self-expandable metal stent (SEMS) migration after endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is a severe complication. The migration risk could be related to the surface friction of SEMS, assumed to be affected by the wire structure and mechanical properties, including radial force (RF); however, their relevance remains unclear. This experimental study aimed to assess the mechanical properties of SEMS involved in the onset of stent migration by measuring the sliding-resistance force (SF) as the SEMS moves through the stomach wall. METHODS: The SF of seven types of 8-mm diameter SEMS (four braided and three laser-cut types) and porcine stomach wall was measured with a universal testing machine. The SF of each SEMS was measured three times, and the average maximum SF (SFmax) was used for analysis. The correlation between SFmax and RF of each SEMS was evaluated. RESULTS: SFmax and RF showed a very strong positive correlation (r = 0.92). Compared to the regression line predictions in the scatter plots of SFmax and RF, the SFmax of laser-cut and braided type SEMSs had positive and negative residuals, respectively. CONCLUSIONS: Selecting a laser-cut type SEMS with a higher RF may more effectively prevent the onset of stent migration against the stomach wall in EUS-HGS.

Structural factors influencing the clinical performance of 0.025-inch guidewires for pancreatobiliary endoscopy: An experimental study.

Background and study aims To develop a pancreatobiliary endoscopic guidewire with good clinical performance, an understanding of its structure is necessary. This study aimed to investigate the structural factors influencing the clinical performance of pancreatobiliary endoscopic guidewires. Methods Eight types of 0.025-inch guidewires were evaluated. The following structural properties were measured: tip length, tip deflection height, tip weight (TW), ratio of tip core weight to TW, shaft coating type (flat or uneven), outer diameter, and core wire diameter (CWD). Four performance tests were conducted to evaluate shaft stiffness as bending force (BF), shaft lubricity as friction force (FF), torque response as torque response rate (TRR), and seeking ability as total insertion success (TIS) in a technical test using a 3D bile duct model. The correlation coefficients of each variable were analyzed. Results The BF and CWDs were strongly correlated, as well as the FF and CWDs and BF. Among the guidewires with similar CWDs, the guidewires with uneven coating had significantly lower FF than those with flat coating. The TRR was strongly correlated with the CWDs; furthermore, guidewires with lower FF had better TRR. TIS was strongly correlated with the TRR, TWs, and ratio of the tip core weight to TW. Conclusions CWD affects shaft stiffness; CWD and coating type affect shaft lubricity and torque response. Because TRR and TW are correlated with seeking ability, an appropriate combination of core wire thickness, TW, and coating design is required to develop a guidewire with good seeking ability.

Clinical Study of 14 Cases of Bone Augmentation with Selective Laser Melting Titanium Mesh Plates.

Additive manufacturing techniques are being used in the medical field. Orthopedic hip prostheses and denture bases are designed and fabricated based on the patient's computer-aided design (CAD) data. We attempted to incorporate this technique into dental implant bone augmentation. Surgical simulation was performed using patient data. Fourteen patients underwent bone augmentation using a selective laser melting (SLM) titanium mesh plate. The results showed no evidence of infection in any of the 14 patients. In 12 patients, only one fixation screw was used, and good results were obtained. The SLM titanium mesh plate was good adaptation in all cases, with bone occupancy greater than 90%. The average bone resorption of the marginal alveolar bone from the time of dental implant placement to the time of the superstructure placement was 0.69 ± 0.25 mm. Implant superstructures were placed in all cases, and bone augmentation with SLM titanium mesh plates was considered a useful technique.

Castleman Disease in an Older Patient With the Onset of Right Pleural Effusion.

Castleman's disease (CD) is an uncommon lymphoproliferative disorder with various presentations in different age groups. Although CD predominantly affects younger individuals, cases in older people are rare. The presentation of CD can range from asymptomatic to severe. We present the case of a 91-year-old male who reported dyspnea and was subsequently diagnosed with right-sided pleural effusion. The patient's condition deteriorated despite an initial provisional diagnosis of tuberculous pleurisy and multiple interventions. A cervical lymph node biopsy later revealed a diagnosis consistent with the plasma cell type of CD. Considering the patient's age and atypical presentation, this case adds a unique perspective to the limited literature on CD in elderly patients. Its presentation can be highly variable, and pleural effusion is rare. Our case highlights the heterogeneity of CD presentation, particularly in older age groups. The diagnosis of CD requires high suspicion, particularly in non-traditional populations. Clinicians should be aware of the varied presentations of CD, including in older patients. Unexplained pleural effusion, even in older patients, should prompt a broad differential diagnosis, including rare conditions such as CD.

Two Cases of Rapidly Progressive Fatty Liver Disease due to Pancreatic Exocrine Insufficiency without a History of Surgery.

We herein report two cases of rapidly progressive fatty liver (FL) disease due to pancreatic exocrine insufficiency (PEI) without a surgical history. Two women, 59 and 72 years old, with no history of abdominal surgery presented to our hospital with severe anorexia and nausea persisting for one week. Examinations revealed progressive, marked FL disease with hepatomegaly and PEI, for which pancreatic enzyme replacement therapy was effective. Commonly known causes of PEI include chronic pancreatitis, abdominal surgery (e.g. pancreaticoduodenectomy), pancreatic cancer, and obstruction of the pancreatic duct, none of which were present in either of these two cases.

High predictive ability of apparent diffusion coefficient value for wall-invasion pattern of advanced gallbladder carcinoma.

PURPOSE: The wall-invasion pattern classification of advanced gallbladder carcinoma (GBC) has been reported. However, its association with clinical findings remains unclear. We aimed to clarify relationships between clinicopathological characteristics, prognosis, and apparent diffusion coefficient (ADC) values of advanced GBC based on the wall-invasion pattern. METHODS: We reviewed the data of 37 patients who had undergone advanced GBC cholecystectomy at our institution between 2009 and 2021. Clinicopathological findings, prognosis, and ADC values were retrospectively analyzed. RESULTS: Based on the wall-invasion pattern, patients were classified into infiltrative growth (IG) type (n = 22) and destructive growth (DG) type (n = 15). In the DG-type, the incidence of venous invasion (P = 0.027), neural invasion (P = 0.008), and lymph node metastasis (P = 0.047) was significantly higher than in the IG-type, and recurrent-free survival (RFS) was significantly shorter (P = 0.015); the median RFS was 11.4 months (95% confidence interval, 6.3-16.5 months) in the DG-type and not reached in the IG-type. The ADC value in the DG-type was significantly lower than in the IG-type (median, 1.19 × 10-3 mm2/s vs. 1.86 × 10-3 mm2/s, P < 0.001). The area under the receiver operating characteristic curve for the ADC values to differentiate wall-invasion patterns was 0.95 (95% confidence interval, 0.87-1.00). The optimal cutoff ADC value was 1.45 × 10-3 mm2/s (sensitivity, 92.9%; specificity, 90.9%). CONCLUSIONS: The wall-invasion pattern of advanced GBC is associated with its aggressiveness and prognosis, and can be predicted by ADC values with high accuracy.

Optimized Mouse-on-mouse Immunohistochemical Detection of Mouse ESR2 Proteins with PPZ0506 Monoclonal Antibody.

Despite the physiological significance of ESR2, a lack of well-validated detection systems for ESR2 proteins has hindered progress in ESR2 research. Thus, recent identification of a specific anti-human ESR2 monoclonal antibody (PPZ0506) and its specific cross-reactivity against mouse and rat ESR2 proteins heightened momenta toward development of appropriate immunohistochemical detection systems for rodent ESR2 proteins. Building upon our previous optimization of ESR2 immunohistochemical detection in rats using PPZ0506, in this study, we further aimed to optimize mouse-on-mouse immunohistochemical detection using PPZ0506. Our assessment of several staining conditions using paraffin-embedded ovary sections revealed that intense heat-induced antigen retrieval, appropriate blocking, and appropriate antibody dilutions were necessary for optimization of mouse-on-mouse immunohistochemistry. Subsequently, we applied the optimized immunostaining method to determine expression profiles of mouse ESR2 proteins in peripheral tissues and brain subregions. Our analyses revealed more localized distribution of mouse ESR2 proteins than previously assumed. Moreover, comparison of these results with those obtained in humans and rats using PPZ0506 revealed interspecies differences in ESR2 expression. We expect that our optimized methodology for immunohistochemical staining of mouse ESR2 proteins will help researchers to solve multiple lines of controversial evidence concerning ESR2 expression.

A novel self-assembling peptide hemostatic gel as an option for initial hemostasis in endoscopic sphincterotomy-related hemorrhage: a case series.

Endoscopic sphincterotomy (EST) is a fundamental procedure of therapeutic endoscopic retrograde cholangiopancreatography, with post-EST bleeding as a serious adverse event. Although there are various hemostatic methods for post-EST bleeding, there is no consensus regarding the treatment choice. PuraStat is a novel self-assembling peptide developed as a hemostatic agent. We report six cases of EST-related hemorrhage with initial hemostasis achieved using PuraStat. The cases were observed in four men and two women, with an average age of 77.8 years. EST was performed for biliary drainage in four cases and for stone removal in two cases. Bleeding occurred during the same session as EST in five of six cases, with the remaining case showing bleeding 4 days after EST. As all patients with EST-related hemorrhage presented oozing with stable vital signs, we selected PuraStat as first-line hemostasis in each case. We applied PuraStat using a dedicated catheter with the tip pressed against the bleeding point. Hemostasis was confirmed without additional procedure in all cases. No adverse events were noted after the procedures. As PuraStat hemostasis is effective, feasible, and safe for EST-related hemorrhage, PuraStat may be an option for initial hemostasis, although it is limited to oozing.

Standardized Methods Using EUS-guided Fine-needle Biopsy and a Minimal Medium Creates Three Pancreatic Cancer Organoids.

BACKGROUND/AIM: Recently, endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has been conducted for diagnosing pancreatic ductal adenocarcinoma (PDAC), after which obtained samples were used in organoid cultures. However, no standardized method for PDAC organoid cultures exists. Therefore, to standardize or simplify sample collection and culture methods for PDAC organoids, we performed a floating culture using non-minced specimens obtained by EUS-FNB in a minimal medium, lacking growth factors or inhibitors for pancreatic organoids. PATIENTS AND METHODS: A total of 38 patients with clinically diagnosed PDAC were enrolled in the study. First, EUS-FNB was conducted using a 22- or 25-gauge biopsy needle. Then, a surplus of samples was collected for organoid formation after rapid on-site cytological evaluations of sample adequacy. Subsequently, the established organoids were compared with clinical data and pathological diagnosis, following periodic observations and evaluations for morphology. RESULTS: PDAC organoids were successfully created in 24 of the 38 cases (63.2%), including four cases with pathologically inconclusive EUS-FNB results. Afterward, PDAC organoid morphology was classified into ductal, dormant, and adhesive small cluster (ASC) types. Although the ductal and ASC types were seen separately, they were also seen together in other cases, which we named "mixed type". CONCLUSION: We propose a feasible and straightforward method for establishing organoids, especially for diagnosing PDAC, particularly when the result of EUS-FNB is pathologically inconclusive. Furthermore, PDAC organoids are morphologically classified into three types reported for the first time.

Hypothalamic KNDy neuron expression in streptozotocin-induced diabetic female rats.

Kisspeptin neurons, i.e. KNDy neurons, in the arcuate nucleus (ARC) coexpress neurokinin B and dynorphin and regulate gonadotropin-releasing hormone/luteinizing hormone (LH) pulses. Because it remains unclear whether these neurons are associated with reproductive dysfunction in diabetic females, we examined the expression of KNDy neurons detected by histochemistry in streptozotocin (STZ)-induced diabetic female rats 8 weeks after STZ injection. We also evaluated relevant metabolic parameters - glucose, 3-hydroxybutyrate, and non-esterified fatty acids - as indicators of diabetes progression. Severe diabetes with hyperglycemia and severe ketosis suppressed the mRNA expression of KNDy neurons, resulting in low plasma LH levels and persistent diestrus. In moderate diabetes with hyperglycemia and moderate ketosis, kisspeptin-immunoreactive cells and plasma LH levels were decreased, while the mRNA expression of KNDy neurons remained unchanged. Mild diabetes with hyperglycemia and slight ketosis did not affect KNDy neurons and plasma LH levels. The number of KNDy cells was strongly and negatively correlated with plasma 3-hydroxybutyrate levels. The vaginal smear analysis showed unclear proestrus in diabetic rats 3-5 days after STZ injection, and the mRNA expression of kisspeptin in the ARC was decreased 2 weeks after STZ injection in severely diabetic rats. Kisspeptin neurons in the anteroventral periventricular nucleus (AVPV), which induce an LH surge, were unaffected at 2 and 8 weeks after STZ injection regardless of the diabetes severity. These results suggest that diabetes mellitus progression in females may negatively affect ARC kisspeptin neurons but not AVPV kisspeptin neurons, implicating a potential role of ARC kisspeptin neurons in menstrual disorder and infertility.

Histological Evaluation of Porous Additive-Manufacturing Titanium Artificial Bone in Rat Calvarial Bone Defects.

Jaw reconstruction using an additive-manufacturing titanium artificial bone (AMTAB) has recently attracted considerable attention. The synthesis of a titanium artificial bone is based on three-dimensional computed tomography images acquired before surgery. A histological evaluation of porous AMTAB (pAMTAB) embedded in rat calvarial bone defects was conducted. This study examined three groups: rats implanted with mixed-acid and heat-treated pAMTAB, rats implanted with untreated pAMTAB, and rats with no implant. In both pAMTAB groups, bone defects were created in rat calvarial bones using a 5-mm trephine bar, followed by pAMTAB implantation. The pAMTAB was fixed to the defect using the fitting force of the surrounding bones. The rats were sacrificed at 4, 8, and 16 weeks after implantation, and the skull was dissected. Undecalcified ground slides were prepared and stained with Villanueva Goldner. Compared with the no implant control group, both pAMTAB groups exhibited new bone formation inside the defect, with greater bone formation in the mixed-acid and heat-treated pAMTAB group than in the untreated pAMTAB group, but the difference was not significant. These data suggest that pAMTAB induces bone formation after implantation in bone defects. Bone formation appears to be enhanced by prior mixed-acid and heat-treated pAMTAB.

[Investigation of the Administration Accuracy of an Auto Infusion Device in 18F-FDG PET].

PURPOSE: The administration accuracy of the automated infusion device for the positron emission radiopharmaceutical affects to calculation of the standardized uptake value (SUV) in 18F-fluorodeoxyglucose (18F-FDG) PET examination. The purpose of this study was to investigate the administration error in the clinical use of an automated infusion device for quantitative management in PET examination. METHODS: We assumed clinical use of the automated infusion device and investigated two types of administration errors. First, for investigating the administration error over time in a day (errorday), a total of 13 infusion works were performed every 30 minutes. Second, for investigating the long period administration error (errorperiod), the infusion work was performed once before clinical use of an automated infusion device. The dispensed radioactivity was set to 150 MBq. The administration error was calculated using output values from the automated infusion device and measured values from the dose calibrator. RESULTS: The administration errorday was 0.9±1.3%, and the maximum error was 2.7%. The administration errorperiod was 1.1±2.0%, and the maximum error was 5.9%. CONCLUSION: We investigated the administration error of the automated infusion device. We confirmed the approximately 1% administration error and high-accuracy injection in an automated-device method.

Effect of quantitative values on shortened acquisition duration in brain tumor 11C-methionine PET/CT.

BACKGROUND: The amount of signal decreases when the acquisition duration is shortened. However, it is not clear how this affects the quantitative values. This study aims to clarify the effect of acquisition time shortening in brain tumor PET/CT using 11C-methionine on the quantitative values. METHOD: This study was a retrospective analysis of 30 patients who underwent clinical 11C-methionine PET/CT examination. PET images were acquired in list mode for 10 min. PET images of acquisition duration from 1 to 10 min with 1-min step were reconstructed. We examined the effect on the quantitative values of acquisition duration. We placed a volume of interest to include the entire tumor and regions of interest in the shape of a large crescent in the contralateral hemisphere in 5 contiguous axial slices as normal tissue. Quantitative values examined were maximum, peak, and mean standardized uptake values (SUVmax, SUVpeak, SUVmean), metabolic tumor volume (MTV), and maximum tumor to normal tissue ratio (TNRmax), with each duration compared to that with 10 min. RESULTS: SUVmax, MTV, and TNRmax showed the highest values due to the effects of statistical noise when the acquisition time was 1 min. These values were stable when the acquisition duration was > 6 min. SUVpeak and SUVmean showed mostly consistent values regardless of duration. CONCLUSIONS: SUVmax, MTV, and TNRmax are affected by acquisition time. If the acquisition duration was > 6 min, the fluctuation could be suppressed within 5% in these quantitative values. However, SUVpeak was suggested to be a robust index regardless of the acquisition duration.

Optimization of immunohistochemical detection of rat ESR2 proteins with well-validated monoclonal antibody PPZ0506.

Although there are few well-validated antibodies against ESR2 proteins, a recent validation assessment identified a specific monoclonal antibody against human ESR2 proteins (PPZ0506). Furthermore, our previous study confirmed its cross-reactivity and specificity against rodent ESR2 proteins, enabling the determination of true ESR2 distribution profiles in rodents. Therefore, we aimed to determine optimal conditions for ESR2 detection by PPZ0506 immunostaining and analyze ESR2 distribution in rats. We evaluated several staining conditions using paraffin-embedded and frozen ovary sections. Immunohistochemical staining with PPZ0506 antibody required strong antigen retrieval and appropriate antibody dilution. Subsequent immunohistochemical analysis in multiple tissues under optimized conditions revealed that rat ESR2 proteins are expressed in a more localized manner than previously assumed. Our results suggest that previous immunohistochemical studies using inadequately validated antibodies against ESR2 proteins overestimated their distribution profiles. We expect that optimized immunohistochemical detection with PPZ0506 antibody can help researchers solve several conflicting problems in ESR2 research.