Prospective assessment of probe-based confocal laser endomicroscopy under direct cholangioscopic visualization for biliary strictures that could not be definitively diagnosed using endoscopic retrograde cholangiopancreatography (with video).

The definitive diagnosis of patients with indeterminate biliary strictures remains challenging. Probe-based confocal laser endomicroscopy (pCLE) provides real-time histological assessment of bile duct tissues. Since no previous studies have evaluated the efficacy of pCLE under direct cholangioscopic visualization for biliary strictures that cannot be definitively diagnosed through endoscopic retrograde cholangiopancreatography using fluoroscopy, we prospectively assessed the feasibility and safety of this procedure in three cases. pCLE findings were obtained in three cases, providing accurate diagnoses. Additionally, no adverse event was reported. pCLE under direct cholangioscopic visualization for indeterminate biliary strictures might be feasible and safe, even though these strictures were not previously diagnosed using endoscopic retrograde cholangiopancreatography. Further studies with more cases are warranted to clarify the effectiveness of pCLE under direct cholangioscopic visualization.

Comparison of Local Recurrence Between LEN-TACE and TACE for Hepatocellular Carcinoma According to Lipiodol Accumulation.

Background/Aim: Transarterial chemoembolization (TACE) is the standard treatment for patients with hepatocellular carcinoma in the intermediate stage; however, with advances in systemic therapy, the indications for TACE have gained significance. While lenvatinib (LEN)-TACE offers the potential for good outcomes, local recurrence has not yet been adequately investigated. Therefore, this study investigated local recurrence factors for each type of TACE, focusing on the lipiodol (Lip) value in LEN-TACE and conventional TACE. Patients and Methods: Fifty patients (50 nodes) with hepatocellular carcinoma and a tumor size <7 cm who underwent LEN-TACE or TACE between January 2022 and June 2023 were included in this study to investigate local recurrence and its influencing factors. Results: The local recurrence rate after LEN-TACE was 5.6% at 6 months and 11.5% at 12 months, whereas those after TACE were 6.4% at 6 months and 13.2% at 12 months (p=0.028). There were no significant differences in local recurrence rates according to background liver factors, alpha-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP) values, sex, age, and albumin-bilirubin (ALBI) score. Lipiodol (Lip) values immediately after LEN-TACE were significantly higher than those after TACE alone (p=0.021). Multivariate analysis showed that LEN-TACE had a recurrence hazard ratio of 0.184. Conclusion: LEN-TACE provided good local tumor control. Local recurrence factors included LEN pretreatment, and Lip CT values were higher immediately after LEN-TACE. Thus, LEN-TACE after upfront LEN administration may increase the effectiveness of TACE.

The correlation between tumoral CD8 expression and clinical course in patients with unresectable pancreatic cancer using tissue samples acquired by endoscopic ultrasound-guided tissue acquisition.

BACKGROUND: The aim of this study was to evaluate the correlation between tumoral CD8 expression and the clinical course in patients with unresectable pancreatic ductal adenocarcinoma (PDAC) using tissue samples acquired by endoscopic ultrasound-guided tissue acquisition (EUS-TA). METHODS: Patients with unresectable PDAC who underwent EUS-TA prior to treatment between September 2017 and October 2021 were included. The localization of the CD8-positive areas was qualitatively evaluated. We divided the patients into high and low groups based on the median percentage of CD8-positive areas. The correlation between the number of CD8-positive areas and overall survival was assessed. Furthermore, the response to chemotherapy was assessed in patients who underwent chemotherapy. RESULTS: A total of 169 patients were included in the analysis. The median overall survival was 171 days (95% confidence interval [CI]: 86-401). The median CD8-positive area was 0.10% (95% CI: 0.05-0.26). The median overall survival in the high (≥0.1%) and low (<0.1%) CD8-positive groups were 156 and 213.5 days, respectively (p = .33). The number of CD8-positive areas was not correlated with the overall survival and response to chemotherapy (p = .69). CONCLUSIONS: Tissue samples acquired using EUS-TA from patients with unresectable PDAC showed that CD8 expression did not affect the clinical course of patients.

Comparison of antimicrobial therapy termination in febrile and afebrile patients with acute cholangitis after drainage.

The standard treatment duration for acute cholangitis (AC) involves a 4-7-day antimicrobial treatment post-biliary drainage; however, recent studies have suggested that a ≤ 2-3 days is sufficient. However, clinical practice frequently depends on body temperature as a criterion for discontinuing antimicrobial treatment. Therefore, in this study, we assessed whether patients with AC can achieve successful outcomes with a ≤ 7-day antimicrobial treatment, even with a fever, assuming the infection source is effectively controlled. We conducted a single-center retrospective study involving patients with AC, defined following the Tokyo Guidelines 2018 for any cause, who underwent successful biliary drainage and completed a ≤ 7-day antimicrobial treatment. Patients were categorized into the febrile and afebrile groups based on their body temperature within 24 h before completing antimicrobial treatment. The primary outcome was the clinical cure rate, defined as no initial presenting symptoms by day 14 post-biliary drainage without recurrence or death by day 30. The secondary outcome was a 3-month recurrence rate. Logistic regression with inverse probability of treatment weighting was used. Overall, 408 patients were selected, among whom 40 (9.8%) were febrile. The two groups showed no significant differences in the clinical cure and 3-month recurrence rates. Notably, the subgroups limited to patients with a ≤ 3-day antibiotic treatment duration also showed no differences in these outcomes. Therefore, our results suggest that discontinuing antibiotics within the initially planned treatment period was sufficient for successful drainage cases of AC, regardless of the patient's fever status during the 24 h leading up to termination.

Convolutional neural network transformer (CNNT) for fluorescence microscopy image denoising with improved generalization and fast adaptation.

Deep neural networks can improve the quality of fluorescence microscopy images. Previous methods, based on Convolutional Neural Networks (CNNs), require time-consuming training of individual models for each experiment, impairing their applicability and generalization. In this study, we propose a novel imaging-transformer based model, Convolutional Neural Network Transformer (CNNT), that outperforms CNN based networks for image denoising. We train a general CNNT based backbone model from pairwise high-low Signal-to-Noise Ratio (SNR) image volumes, gathered from a single type of fluorescence microscope, an instant Structured Illumination Microscope. Fast adaptation to new microscopes is achieved by fine-tuning the backbone on only 5-10 image volume pairs per new experiment. Results show that the CNNT backbone and fine-tuning scheme significantly reduces training time and improves image quality, outperforming models trained using only CNNs such as 3D-RCAN and Noise2Fast. We show three examples of efficacy of this approach in wide-field, two-photon, and confocal fluorescence microscopy.

Decreased Abundance of Genus Slackia in Individuals With Obesity and Colorectal Adenoma.

Background and Aims: The increasing prevalence of obesity has significantly contributed to the global burden of colorectal cancer and the precancerous colorectal adenoma (CRA). Gut microbiota vary at each stage of colorectal carcinogenesis and participate in energy homeostasis. Elucidating gut microbiotal characteristics in obesity-related CRA may help prevent and treat colorectal tumors; however, this remains unclarified. Therefore, this study investigated the gut microbiota profile of patients with obesity-related CRA. Methods: This hospital setting-based cross-sectional study included 113 participants (66 [without CRA control group] and 37 [with CRA group]; each group was divided into obese and nonobese groups) who underwent screening colonoscopy between June 2019 and January 2020. Gut microbiota were analyzed using 16S rRNA and polymerase chain reaction techniques and the data compared between the aforementioned groups. Results: No between-group difference was observed in the diversity index; however, α diversity was the lowest in the obese CRA group. The CRA group had significantly higher and lower numbers of 26 and 17 genera, respectively. Genus Slackia was significantly lower in the obese CRA group than in the nonobese CRA group. Multivariate analysis of the quartiles according to genus Slackia relative abundance rates revealed that the first quartile was an independent risk factor for CRA (odds ratio, 3.57; 95% confidence interval 1.19-10.7). The proportion of equol reductase-positive participants was lowest in the obese CRA group (P = .04). Multivariate odds ratio for CRA was 5.46 (95% confidence interval 1.35-22.0) for genus Slackia and equol reductase-negative participants. Conclusion: Decreased abundance of genus Slackia and absence of equol reductase potentially influence obesity-related CRA development.

Prevalence of social frailty in patients with rheumatoid arthritis: data from a multicenter observational study (T-FLAG study).

BACKGROUND: This study aimed to investigate the prevalence of social frailty and associated factors. METHODS: A total of 655 consecutive patients who were able to complete the Kihon Checklist (KCL) and the Questionnaire on Social Frailty between June and August 2022 were enrolled. Social frailty was assessed using the Makizako Social Frailty Index. Patient characteristics were analyzed by analysis of variance. Factors associated with social frailty were analyzed using multivariate logistic analysis. Spearman's rank correlation coefficients were used to examine correlations between each KCL domain and social frailty. RESULTS: Mean age was 68 years, and disease duration was 12 years; 73% of patients were female. Social frailty was present in 30.8% of patients, with 36.5% classified as social pre-frailty. Multivariate analysis revealed age and HAQ-DI to be independent factors associated with social frailty. The proportion of social frailty increased with increasing age and worsening HAQ-DI scores. The KCL domain "Isolation" was the most strongly associated with social frailty (r = 0.601, P < 0.001), with higher scores associated with a higher proportion of social frailty. CONCLUSIONS: Social frailty in RA patients is associated with age and physical impairment (HAQ-DI). Moreover, the KCL domain "Isolation" was strongly associated with social frailty.

Clinical features of juvenile onset ankylosing spondylitis in Japanese patients.

OBJECTIVES: This retrospective study aimed to examine the clinical features of juvenile onset ankylosing spondylitis (JoAS) in Japanese patients. METHODS: We examined clinical symptoms (including initial symptoms) and the progression to diagnosis of AS in 17 Japanese JoAS patients at our institute between January 2004 and May 2023. Initial symptoms were considered pain at axial joints and/or extra-axial joints. RESULTS: Mean ages (± standard deviation) at onset and diagnosis of AS were 12.9 (± 2.0) years and 19.6 (± 9.6) years, respectively. The back was the most common site of initial symptoms (seven patients; 41.2%), followed by the hip (five patients; 29.4%) and knees (five patients; 29.4%). Initial symptoms were limited to extra-axial joints and axial joints in nine (52.9%) and seven (41.2%) patients, respectively. Nine patients (52.9%) were recognised as a musculoskeletal disease other than AS, such as oligoarticular juvenile idiopathic arthritis. CONCLUSIONS: Sites of initial symptoms were frequently the back, hip, and knees, with 52.9% of patients having initial symptoms limited to extra-axial joints. More than half of the patients were recognised musculoskeletal diseases other than AS.

Determinants of Survival of Ablation Treatment for Portal Vein Tumor Thrombus in Patients With Hepatocellular Carcinoma.

BACKGROUND/AIM: The prognosis of hepatocellular carcinoma (HCC) complicated with portal vein tumor thrombus (PVTT) is extremely poor. This study investigated whether local ablation-a curative treatment similar to resection-could improve the prognosis of patients with Child-Pugh B/C PVTT. PATIENTS AND METHODS: Between January 2020 and December 2023, 25 patients with Child-Pugh B/C PVTT HCC were enrolled, and their overall survival with radiofrequency ablation treatment and the associated drivers were investigated. RESULTS: Overall survival (median 282 days) differed between the group treated with transarterial chemoembolization (TACE, 285 days) and the group without it (159 days, p=0.0151). The median survival in the esophagogastric variceal exacerbation group (120.5 days) was shorter than that in the non-exacerbation group (284.0 days, p=0.00964). In multivariate analysis, concomitant TACE had a hazard ratio (HR) of 0.121 (p=0.0097), and the exacerbation of esophagogastric varices had a HR of 6.761 (p=0.01). CONCLUSION: Local ablation for PVTT may promote patient survival specifically by inhibiting the exacerbation of portal hypertension in patients with hepatocellular carcinoma.

Transglutaminase-mediated proximity labeling of a specific Lys residue in a native IgG antibody.

The fusion protein of an engineered zymogen of microbial transglutaminase (EzMTG) with a protein G variant, EzMTG-pG, enabled the proximity-based, tag-free labeling of Lys65 in the heavy chain of a native IgG antibody (trastuzumab) with a Gln-donor peptidyl substrate functionalized with a fluorescent molecule.

Preoperative factors predicting poor therapeutic efficacy of holmium laser enucleation of the prostate in patients with benign prostatic hyperplasia.

OBJECTIVES: We assessed preoperative factors predicting the poor therapeutic efficacy of holmium laser enucleation of the prostate (HoLEP) in benign prostatic hyperplasia (BPH) patients. METHODS: The present study included 159 patients who underwent HoLEP between August 2015 and June 2021 at our institution. Overall therapeutic efficacy was divided into good and poor therapeutic efficacies according to changes in the international prostate symptom score (IPSS), IPSS quality of life (IPSS-QOL), and the maximum urinary flow rate. Patients were divided into good and poor therapeutic efficacy groups based on findings obtained 3 months after HoLEP, and comparative assessments were performed between the two groups. RESULTS: The therapeutic efficacy of HoLEP was poor in 53 (33.3%) out of 159 patients. Intravesical prostatic protrusion (IPP), IPSS, IPSS-QOL, post-void residual volume (PVR), and the presence of overactive bladder (OAB) were significantly higher in the poor therapeutic efficacy group than in the good therapeutic efficacy group. A multivariable analysis of several factors identified the preoperative presence of OAB and short IPP as independent risk factors for the poor therapeutic efficacy of HoLEP. When treatment efficacy was divided according to risk factors, poor therapeutic efficacy was observed in only 14% of patients with prolonged IPP and the absence of OAB. CONCLUSIONS: The therapeutic efficacy of HoLEP may be poor in patients with OAB and short IPP, resulting in the significant deterioration of lower urinary tract symptoms. Accordingly, it is important to consider the presence or absence of OAB and IPP measurements when selecting indications for HoLEP.

Real-world retrospective analysis of immune checkpoint inhibitor therapy for relapsed or refractory Hodgkin's lymphoma.

Immune checkpoint inhibitors (ICI) are promising therapeutic agents for relapsed or refractory classical Hodgkin's lymphoma (RRcHL). This retrospective study evaluated patients with RRcHL registered in the clinical research program Tohoku-Hematology-Forum-26, between 2016 and 2020, and treated with ICI in 14 centers in Northeast Japan. We analyzed the usage, efficacy, and safety of ICI therapy (ICIT). Among a total of 27 patients with RRcHL, 21 and nine were treated with nivolumab and/or pembrolizumab, respectively. The best response was complete response (CR), partial response (PR), stable disease (SD), and progressive disease in 11 (40.8%), seven (25.9%), eight (29.6%), and one (3.7%) patient, respectively. In all patients undergoing ICIT, the 2-year progression-free survival and 2-year overall survival (OS) were 48.6% and 87.4%, respectively. The 2-year OS for patients with CR, PR, and SD were 100%, 68.6%, and 87.5%, respectively. A total of 36 events of immune-related adverse events (irAEs) or immune-related like adverse events (irlAEs) were observed in 19 of the 27 patients (70.4%). Two thirds of these irAEs or irlAEs were grade 1-2 and controllable. During the observation period, ICIT was discontinued in 22 of 27 (81.4%) patients due to CR, inadequate response, irAE and patient circumstances in five (22.7%), seven (31.8%), eight (36.4%) and two patients (9.1%), respectively. Therapy-related mortality-associated irAE were observed in only one patient during ICIT. These results suggest that ICIT for RRcHL is effective and safe in real-world settings. The optimal timing of induction and duration of ICIT remains to be established.

Minimally Invasive Trans-sacral Canal Plasty for Lumbar Canal Stenosis.

Objective The elderly population is increasing in Japan. Along with the increase in the elderly population, the number of patients with lumbar degenerative diseases is also on the rise. In general, elderly patients tend to have more complications and are at higher risk for surgery. Many elderly people suffer from lumbar degenerative disease. We reviewed our initial experience with trans-sacral canal plasty (TSCP) for patients with lumbar spinal canal stenosis and examined the pertinent literature for this report. Methods An analytical observational study was performed on 120 patients with lumbar spinal canal stenosis who underwent TSCP at our single institution from March 2019 to October 2021. These patients had leg pain and/or lower back pain due to degenerative lumbar disease. Patients who had coagulation abnormality, pregnancy, contrast allergy, pyogenic spondylitis, or spinal metastasis were excluded. Results Immediately after TSCP, the average Visual Analog Scale (VAS) score for back pain improved from 58.2 to 29.3, and for leg pain from 72.0 to 31.3. Two years after TSCP, the average VAS score for back pain increased slightly and the average score for leg pain remained almost the same. Additional surgery was performed in 37 of 120 (31%) patients who underwent TSCP. The additional surgery group had significantly worse back pain at one and three months postoperatively than the conservative treatment group. The additional surgery group had significantly worse leg pain immediately after TSCP and at one and three months postoperatively than the conservative treatment group. Logistic regression analysis demonstrated that a decreased spinal canal area (OR 0.986, p = 0.039) was associated with additional surgery. Conclusions We reviewed the outcomes of TSCP at our hospital. The average VAS score for back pain and leg pain improved. However, 31% of patients who underwent TSCP required additional surgery. It was found that the spinal canal area was a major factor in the need for additional surgery.

Convolutional Neural Network Transformer (CNNT) for Fluorescence Microscopy image Denoising with Improved Generalization and Fast Adaptation.

Deep neural networks have been applied to improve the image quality of fluorescence microscopy imaging. Previous methods are based on convolutional neural networks (CNNs) which generally require more time-consuming training of separate models for each new imaging experiment, impairing the applicability and generalization. Once the model is trained (typically with tens to hundreds of image pairs) it can then be used to enhance new images that are like the training data. In this study, we proposed a novel imaging-transformer based model, Convolutional Neural Network Transformer (CNNT), to outperform the CNN networks for image denoising. In our scheme we have trained a single CNNT based "backbone model" from pairwise high-low SNR images for one type of fluorescence microscope (instance structured illumination, iSim). Fast adaption to new applications was achieved by fine-tuning the backbone on only 5-10 sample pairs per new experiment. Results show the CNNT backbone and fine-tuning scheme significantly reduces the training time and improves the image quality, outperformed training separate models using CNN approaches such as - RCAN and Noise2Fast. Here we show three examples of the efficacy of this approach on denoising wide-field, two-photon and confocal fluorescence data. In the confocal experiment, which is a 5×5 tiled acquisition, the fine-tuned CNNT model reduces the scan time form one hour to eight minutes, with improved quality.

Real-world experience of Doxorubicin Monotherapy for Advanced or Metastatic Retroperitoneal Sarcoma: A Single Institutional Study of 16 Cases.

BACKGROUND/AIM: Anthracycline-based chemotherapies including doxorubicin monotherapy are recommended in major guidelines for patients with advanced or metastatic retroperitoneal sarcoma (RPS); however, few studies have reported the outcomes of doxorubicin monotherapy for these patients. We herein investigated the oncological efficacy and safety of doxorubicin monotherapy for patients with advanced or metastatic RPS in real-world clinical practice. PATIENTS AND METHODS: Sixteen patients diagnosed with advanced or metastatic retroperitoneal sarcoma, receiving doxorubicin monotherapy as first-line treatment between February 2017 and March 2023 at our Institution were analyzed. Response rate, progression-free survival (PFS) periods, overall survival (OS) period, and adverse event (AE) profiles were retrospectively investigated. RESULTS: The median age of patients was 69.5 years. Best responses to doxorubicin were as follows: complete response, 0 patients (0.0%); partial response, 3 (18.8%); stable disease, 9 (56.3%); and progressive disease, 4 (25.0%). The objective response rate and disease control rate were 18.8 and 75.0%, respectively. During the observation period (median, 22 months, range=2-53 months), median PFS and OS periods were 8.0 and 24.0 months, respectively. The following AEs Grade ≥3 occurred: neutropenia in 14 patients (87.5%), febrile neutropenia in 5 (31.3%), leukopenia in 2 (12.5%), thrombocytopenia in 1 (6.3%), and heart failure in 1 (6.3%). Grade ≥3 nausea and vomiting did not occur and there was no treatment-related death. CONCLUSION: The oncological outcomes of doxorubicin monotherapy for RPS in real-world clinical practice were not inferior to those of the EORTC trial. The incidence of hematological AEs was higher; however, severe gastrointestinal AEs were prevented by prophylactic antiemetics and there were no treatment-related deaths. Collectively, doxorubicin monotherapy with appropriate prophylactic agents is a valid option for patients with advanced or metastatic RPS.

Decrease in the usual walking speed and body fat percentage associated with a deterioration in long-term care insurance certification levels.

Background: In Japan, the number of older adults requiring long-term care insurance (LTCI) is increasing and the cost is becoming a social problem. In these fields, the role of geriatric rehabilitation includes maintaining the physical function and LTCI certification levels. The prevalence of sarcopenia is high among older adults requiring LTCI certification, and there are many opportunities to assess the handgrip strength, walking speed, and muscle mass. This study aimed to identify sarcopenia-related assessments sensitive to transitions in LTCI certification levels and determine cut-off values to predict them. Methods: This prospective cohort study analyzed 98 daycare users (mean age ± standard error: 78.5 ± 0.8 years) between March 2019 and 2023. The participants received LTCI certification before the study, and their levels were renewed between baseline and follow-up (six months later). The measurements included handgrip strength, usual walking speed, body composition, and SARC-F score. Participants were classified into maintenance, deterioration, and improvement groups according to the changes in their LTCI certification levels. We identified factors contributing to the deterioration of LTCI certification levels using baseline and before and after comparisons, multivariate analyses, and receiver operating characteristic analyses. Results: No significant differences were observed in the baseline data among the groups. Only the deterioration group showed significant changes in the usual walking speed (baseline: 0.64 ± 0.25 m/s, follow-up: 0.53 ± 0.21 m/s, P = 0.008) and body fat percentage (baseline: 29.2 ± 9.9%, follow-up: 27.7 ± 10.3%, P = 0.047). Binomial logistic regression showed that changes in usual walking speed (P = 0.042) and body fat percentage (P = 0.011) were significantly associated with the deterioration of LTCI certification levels, even after adjustment. The cutoff values of change to discriminate the deterioration of LTCI certification levels were -0.14 m/s at the usual walking speed (P = 0.047) and -1.0% for body fat percentage (P = 0.029). Conclusions: Decreases in usual walking speed and body fat percentage may predict worse certification levels in older adults requiring LTCI.

Efficacy of Short-Course Antibiotic Therapy for Acute Cholangitis With Positive Blood Cultures: A Retrospective Study.

BACKGROUND: Short-term treatment of acute cholangitis is sufficient for cure compared with the standard treatment duration. Whether this short-course antimicrobial therapy is effective in patients with acute cholangitis with positive blood cultures has not been fully investigated. This study assessed whether patients with acute cholangitis could achieve successful outcomes with a three-day or shorter antimicrobial treatment period, even with a positive blood culture. METHODS: This single-center retrospective study involved patients with acute cholangitis, defined according to the Tokyo Guidelines 2018 for any cause, who underwent successful biliary drainage and completed a seven-day or shorter antimicrobial treatment. Patients were categorized into six groups based on the duration of antibiotic use (short or standard) after endoscopic retrograde cholangiopancreatography and blood culture findings (positive, negative, or no collection). The primary outcome was the clinical cure rate, defined as no initial presenting symptoms by day 14 after biliary drainage and no recurrence or death by day 30. Secondary outcomes included a three-month recurrence rate and length of hospital stay. RESULTS: In total, 389 cases were selected, and 27 patients (6.9%) undergoing short-course therapy tested positive for blood culture. The clinical cure rate (n=25, 92.6%) in this group was comparable to that in the other groups. For the three-month recurrence rate (n=1, 3.7%) and median hospital stay (six days), this group's outcomes were either better or similar to those of the other groups. CONCLUSIONS: For cases of successful drainage in acute cholangitis, even with positive blood cultures, short-term antibiotic therapy may be appropriate.