Search

Background: Long‐term management of moderate‐to‐severe psoriasis is usually discussed in terms of continuous administration; however, there are many situations in clinical practice where treatment may be withdrawn with subsequent retreatment. Objective: To assess the clinical course after ixekizumab treatment withdrawal and retreatment, as well as the effectiveness of ixekizumab retreatment, in Japanese patients with plaque psoriasis. Methods: This single‐arm, open‐label study (UNCOVER‐J; NCT01624233) comprised 78 patients with plaque psoriasis. After ixekizumab treatment (160‐mg loading dose, 80 mg every 2 weeks for the first 12 weeks, and then 80 mg every 4 weeks (IXE Q4W) until Week 52), 70 patients achieved a Psoriasis Area Severity Index (PASI)75 response at Week 52. These 70 patients withdrew from ixekizumab treatment from Weeks 52 to 100. Patients who relapsed (PASI ≤50) during the Treatment Withdrawal Period were retreated with IXE Q4W for 192 weeks. Results: At Weeks 52, 76 and 100, PASI75 response rates were 100%, 26% and 7%; PASI90 response rates were 87%, 11% and 3%; and PASI100 response rates were 53%, 0% and 0%. After treatment withdrawal, 87% of patients relapsed; median time to relapse was 143 days. After 12 weeks of retreatment with IXE Q4W, 83% of relapsed patients achieved PASI75, 68% achieved PASI90 and 25% achieved PASI100; improvements were maintained up to 120 weeks of retreatment. Treatment‐emergent adverse events and serious adverse events were reported in 56% and 4% of patients during the Treatment Withdrawal Period, and in 88% and 14% of patients during the Retreatment Period. Conclusion: In patients withdrawn from ixekizumab after achieving PASI75, approximately half relapsed within 5 months of withdrawal; however, most patients recaptured response within 12 weeks, and response was maintained for up to 120 weeks of retreatment. [ABSTRACT FROM AUTHOR]

Background: Erythrodermic and generalized pustular psoriasis are rare, difficult to treat forms of psoriasis. In previous reports, we documented 24‐ and 52‐week findings of an open‐label, phase 3 trial (UNCOVER‐J) of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis; most patients responded to treatment and maintained response through 52 weeks. Objective: To assess the long‐term (>3 years) efficacy and safety of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis. Methods: These subgroup analyses were of a partial population of patients from UNCOVER‐J (NCT01624233; Sponsored by Eli Lilly and Company), specifically those with erythrodermic psoriasis (N = 8) or generalized pustular psoriasis (N = 5). These patients received 160 mg ixekizumab at Week 0, ixekizumab 80 mg every 2 weeks through Week 12, and ixekizumab 80 mg every 4 weeks thereafter up to Week 244. This regimen is consistent with the regimen approved in Japan for plaque, erythrodermic, and generalized pustular psoriasis and psoriatic arthritis. Efficacy assessments included Global Improvement Score (GIS), Psoriasis Area and Severity Index (PASI), dermal symptoms (for patients with generalized pustular psoriasis), Dermatology Life Quality Index (DLQI) and Itch Numeric Rating Scale (NRS). Safety assessments included treatment‐emergent adverse events and adverse events of special interest. Results: Most patients had a GIS of resolved or improved from Week 12 onwards, and all patients had early and sustained improvement in PASI and dermal symptom (generalized pustular psoriasis only) scores. Mean improvements in DLQI and Itch NRS at Week 12 were sustained through Week 244. Ixekizumab was well tolerated over 3 years of treatment in patients with erythrodermic psoriasis or generalized pustular psoriasis, and no new safety concerns were identified. Conclusion: These findings suggest that ixekizumab can be an effective long‐term treatment option for erythrodermic or generalized pustular psoriasis. Linked article: This article is commented on G. Egawa et al., p. 259 in this issue. To view this article visit https://doi.org/10.1111/jdv.15416 [ABSTRACT FROM AUTHOR]

Physiochemical assessment of the parasite-biomaterial interface is essential in the development of new biomaterials. The purpose of this study was to develop a method to evaluate pH at the bacteria-dental cement interface and to demonstrate physiochemical interaction at the interface. The experimental apparatus with a well (4.0 mm in diameter and 2.0 mm deep) was made of polymethyl methacrylate with dental cement or polymethyl methacrylate (control) at the bottom. Three representative dental cements (glass-ionomer, zinc phosphate, and zinc oxide-eugenol cements) were used. Each specimen was immersed in 2 mM potassium phosphate buffer for 10 min, 24 hrs, 1 wk, or 4 wks. The well was packed with Streptococcus mutans NCTC 10449, and a miniature pH electrode was placed at the interface between bacterial cells and dental cement. The pH was monitored after the addition of 1% glucose, and the fluoride contained in the cells was quantified. Glass-ionomer cement inhibited the bacteria-induced pH fall significantly compared with polymethyl methacrylate (control) at the interface (10 min, 5.16 ± 0.19 vs. 4.50 ± 0.07; 24 hrs, 5.20 ± 0.07 vs. 4.59 ± 0.11; 1 wk, 5.34 ± 0.14 vs. 4.57 ± 0.11; and 4 wks, 4.95 ± 0.27 vs. 4.40 ± 0.14), probably due to the fluoride released from the cement. This method could be useful for the assessment of pH at the parasite-biomaterial interface. [ABSTRACT FROM AUTHOR]

Purpose: We compared the diagnostic accuracy of fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and PET/magnetic resonance imaging (MRI) fusion images for gynecological malignancies.Materials and Methods: A total of 31 patients with gynecological malignancies were enrolled. FDG-PET images were fused to CT, T1- and T2-weighted images (T1WI, T2WI). PET-MRI fusion was performed semiautomatically. We performed three types of evaluation to demonstrate the usefulness of PET/MRI fusion images in comparison with that of inline PET/CT as follows: depiction of the uterus and the ovarian lesions on CT or MRI mapping images (first evaluation); additional information for lesion localization with PET and mapping images (second evaluation); and the image quality of fusion on interpretation (third evaluation).Results: For the first evaluation, the score for T2WI (4.68 +/- 0.65) was significantly higher than that for CT (3.54 +/- 1.02) or T1WI (3.71 +/- 0.97) (P < 0.01). For the second evaluation, the scores for the localization of FDG accumulation showing that T2WI (2.74 +/- 0.57) provided significantly more additional information for the identification of anatomical sites of FDG accumulation than did CT (2.06 +/- 0.68) or T1WI (2.23 +/- 0.61) (P < 0.01). For the third evaluation, the three-point rating scale for the patient group as a whole demonstrated that PET/T2WI (2.72 +/- 0.54) localized the lesion significantly more convincingly than PET/CT (2.23 +/- 0.50) or PET/T1WI (2.29 +/- 0.53) (P < 0.01).Conclusion: PET/T2WI fusion images are superior for the detection and localization of gynecological malignancies. [ABSTRACT FROM AUTHOR]

This study evaluated acid production from cooked starch by Streptococcus mutans, Streptococcus sobrinus, Streptococcus sanguinis and Streptococcus mitis, and the effects of alpha-amylase inhibitors (maltotriitol and acarbose) and xylitol on acid production. Streptococcal cell suspensions were anaerobically incubated with various carbohydrates that included cooked potato starch in the presence or absence of alpha-amylase. Subsequently, the fall in pH and the acid production rate at pH 7.0 were measured. In addition, the effects of adding alpha-amylase inhibitors and xylitol to the reaction mixture were evaluated. In the absence of alpha-amylase, both the fall in pH and the acid production rate from cooked starch were small. On the other hand, in the presence of alpha-amylase, the pH fell to 3.9-4.4 and the acid production rate was 0.61-0.92 micromol per optical density unit per min. These values were comparable to those for maltose. When using cooked starch, the fall in pH by S. sanguinis and S. mitis was similar to that by S. mutans and S. sobrinus. For all streptococci, alpha-amylase inhibitors caused a decrease in acid production from cooked starch, although xylitol only decreased acid production by S. mutans and S. sobrinus. These results suggest that cooked starch is potentially acidogenic in the presence of alpha-amylase, which occurs in the oral cavity. In terms of the acidogenic potential of cooked starch, S. sanguinis and S. mitis were comparable to S. mutans and S. sobrinus. Alpha-amylase inhibitors and xylitol might moderate this activity. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the diagnostic accuracy of positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) for staging/restaging, evaluating the treatment response, and screening of recurrence in patients with malignant lymphoma (ML) during long-term follow-up, and to compare that with computer tomography (CT)/magnetic resonance imaging (MRI). Methods: The study was conducted in 59 ML patients who underwent whole-body 18F-FDG-PET examinations three times or more from October 1998 to August 2006. The location of the lesions in the patients with positive findings on 18F-FDG-PET and/or the corresponding CT/MRI was classified into supradiaphragmatic (n = 10), infradiaphragmatic (n = 7), and extranodal sites (n = 20), and the findings were compared on a site basis according to the gold standard, which consisted of all clinical information available, including follow-up results. Results: A total of 156 18F-FDG-PET examinations for which the corresponding CT/MRI images were also available were evaluated, and a total of 305 sites showed positive findings on 18F-FDG-PET and/or CT/MRI. Concordant positive findings were obtained in 76% for staging/restaging, 34% for evaluation of the treatment response, and 50% for screening of recurrence. The accuracy of 18F-FDG-PET versus CT/MRI was 92% versus 84% (P = 0.06) for staging/restaging, 84% versus 50% (P < 0.05) for the evaluation of the treatment response, and 83% versus 72% (P = 0.21) for the screening of recurrence. At pathologic sites with discrepant findings between 18F-FDG-PET and CT/MRI (n = 122), the frequency of accurate diagnosis by 18F-FDG-PET (76%) was higher than that by CT/MRI (24%), especially for the evaluation of the treatment response. Conclusions: 18F-FDG-PET is expected to play a significant role in the management of ML patients even after effective treatment is initiated. [ABSTRACT FROM AUTHOR]

Treatment for lung cancer continues to rapidly evolve. Here, we describe trends in the initial treatment of adults with newly diagnosed primary non-small-cell lung cancer in Japan. This retrospective cohort study used data from JMDC Inc. Claims Database from 2015 to 2023. Adults with lung cancer, confirmed using a combination of diagnosis, treatment, or procedure codes, were enrolled. A total of 9373 patients were included, with a mean age of approximately 59 years. The median time from diagnosis to treatment initiation ranged from 38 days in patients treated surgically to 25 days in patients with distant metastases. The observed trends were a decrease in the percentage of newly diagnosed patients with distant metastases, a decline in chemotherapy use in patients with early-stage disease, and in advanced disease, a more than doubling in the use of targeted therapy, including checkpoint inhibitors, while radiotherapy and chemotherapy tended to decrease. The observed changes in treatment were driven mainly by the increased use of targeted therapies including checkpoint inhibitors and are aligned with current treatment guidelines in Japan. The observation of fewer patients with distant metastases over time possibly indicates earlier detection. Additional research is needed to understand if new therapies are being extended to older and frail patients with lung cancer in Japan.

Background/aims: There are few studies that comprehensively report real-world persistence for first-line advanced therapies used to treat inflammatory bowel disease. We aimed to describe persistence of first-line advanced therapies among incident biologic or Janus kinase inhibitor users with inflammatory bowel disease., Methods: Retrospective cohort study using the Japan Medical Data Center database from January 1, 2010, until September 30, 2022. Patients aged ≥15 years with relevant diagnostic and treatment codes were included. All eligible patients were observed until study end (September 30, 2022), death, or disenrollment, whichever occurred first., Results: Among 1,115 patients with Crohn's disease included in the analysis, 41.4% initiated adalimumab, 37.4% infliximab, 18.1% ustekinumab, and 3.0% vedolizumab. Median age was 31.2-34.8 years, 72.8% to 85.9% were male. Persistence at 12 months was 84.7% for adalimumab, 87.7% for infliximab, 91.3% for ustekinumab, and 53.1% for vedolizumab. Persistence at 24 months was 76.3%, 76.8%, 80.4%, and 28.6%, respectively. Among 1,942 patients with ulcerative colitis, 24.8% initiated adalimumab, 33.6% infliximab, 11.2% golimumab, 17.5% vedolizumab, 5.6% ustekinumab, and 7.3% tofacitinib. Mean age was 38.2-40.4 years, 57.4% to 65.8% were male. Persistence at 12 months was 57.6% for adalimumab, 87.7% for infliximab, 54.9% for golimumab, 69.7% for vedolizumab, and 84.0% for ustekinumab. At month 24, persistence for ustekinumab was 75.0%, versus 42.9%-59.4% for other treatments., Conclusions: Index treatment with ustekinumab resulted in high persistence through 24 months after initiation in patients with Crohn's disease or ulcerative colitis. Our study provides insights into the real-world usage of advanced treatments for patients with IBD in Japan.

Surgery of lesions around Wernicke's area is challenging for several reasons. The anatomical boundaries are not clearly defined, necessitating functional identification in addition to anatomical landmarks. There are potential complications secondary to injury of the surrounding structures. This challenge is more substantial when dealing with lower-grade gliomas in this region, as surgeons must balance the extent of resection with the risk of potential injury to the patient, especially considering that there may be other treatment options for the management of residual tumors. In this video, the authors present a case illustration, discussing surgical considerations and strategy. The video can be found here: https://stream.cadmore.media/r10.3171/2024.10.FOCVID24101., Competing Interests: Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this publication.The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this publication., (© 2025, The Authors.)

Background: Fecal immunochemical tests are commonly performed for colorectal cancer screening. Instant fecal occult blood measurement in toilet bowel movements would improve convenience. Hyperspectral imaging (HSI) enables the nondestructive evaluation of materials that are difficult to assess visually. This study aimed to determine whether HSI could be used to identify fecal occult blood on stool surfaces., Methods: The study included 100 patients who underwent colonoscopy, divided into groups A and B (50 patients, each) for creating a discriminant algorithm and validating the accuracy of the algorithm, respectively. In group A, 100 areas were randomly selected from the stool surface, and the fecal occult blood quantitative values were measured and photographed using a hyperspectral camera (cutoff: > 400 ng/mL). A discriminant algorithm image was created to extract spectral feature differences obtained from HSI via machine learning. In group B, 250 random areas were evaluated and compared to fecal occult blood quantitative values, measuring sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV)., Results: Groups A and B comprised 28 and 26 patients with cancer, respectively. Cancer detection sensitivity at the 400 ng/mL cutoff was 67.9% and 42.3% in groups A and B, respectively. The discriminant algorithm image exhibited high accuracy in group A (sensitivity; 77.1%, specificity; 96.9%, accuracy; 90.0%, PPV; 93.1%, NPV; 88.7%). In group B, the sensitivity, specificity, accuracy, PPV, and NPV were 83.3, 92.9, 90.8, 76.3, and 95.3%, respectively., Conclusion: HSI can effectively discriminate high quantitative fecal occult blood, highlighting its potential for improved colorectal cancer screening., Competing Interests: Declarations. Conflict of interest: None of the authors has any financial relationships relevant to this publication to disclose., (© 2024. The Author(s).)

The KCNE family (KCNE1-5) is a group of single transmembrane auxiliary subunits for the voltage-gated K + channel KCNQ1. The KCNQ1-KCNE complexes are crucial for numerous physiological processes including ventricular repolarization and K + recycling in epithelial cells. We identified a new member of the KCNE family, "KCNE6", from zebrafish. We found that KCNE6 is expressed in the zebrafish heart and is involved in cardiac excitability. When co-expressed with KCNQ1, KCNE6 produces a slowly activating current like the slow delayed-rectifier K + current (I Ks ) induced by KCNE1, despite the fact that the KCNE6 amino acid sequence has the highest similarity to that of KCNE3, which forms a constitutively open channel with KCNQ1. The kcne6 nucleotide sequences exist throughout vertebrates, including humans, although only the KCNE6 proteins of lower vertebrates, up to marsupials, can modulate KCNQ1, and it has become a pseudogene in eutherians. Our findings will facilitate a better understanding of how the KCNE family has evolved to modulate KCNQ1., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background and Aim: Endoscopic resection (ER) is widely performed to treat early colorectal cancer. However, additional surgery for pathological T1 colorectal cancer (pT1CRC) after ER is controversial because of the imprecise prediction of lymph node metastasis (LNM). Recently, several patients of pT1CRC with lymphoid follicular replacement (LFR) without LNM have been reported. This study aimed to investigate the clinicopathological features and risk of LNM in patients with pT1CRC with LFR., Methods: We retrospectively analyzed patients who underwent ER or surgical resection and were diagnosed with pT1CRC between January 2010 and December 2020. We defined pT1CRC with LFR as the replacement of a part of the lymphoid follicular component within the submucosal area by adenocarcinoma, with no invasion into other submucosal areas., Results: Among the 600 eligible patients, the incidence rate of pT1CRC with LFR was 6.7% (40/600). Patients with pT1CRC with LFR represented 14.3% (37/258) of the endoscopically treated patients and 0.9% (3/342) of the surgically treated patients. For patients with pT1CRC with LFR, 80.0% (32/40) had flat and depressed lesions, and 35.0% (14/40) had submucosal invasion depth ≥1000 μm. Patients with pT1CRC with LFR had negative lymphovascular invasion, differentiated type, and budding grade 1. In the median follow-up of 61 months, patients with pT1CRC with LFR had no LNM., Conclusions: The presence of LFR in pT1CRC may be associated with a low risk of LNM. In patients with pT1CRC with LFR, follow-up without additional surgery is possible even if the submucosal invasion depth is ≥1000 μm., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objectives: Colonoscopy (CS) is an important screening method for the early detection and removal of precancerous lesions. The stool state during bowel preparation (BP) should be properly evaluated to perform CS with sufficient quality. This study aimed to develop a smartphone application (app) with an artificial intelligence (AI) model for stool state evaluation during BP and to investigate whether the use of the app could maintain an adequate quality of CS., Methods: First, stool images were collected in our hospital to develop the AI model and were categorized into grade 1 (solid or muddy stools), grade 2 (cloudy watery stools), and grade 3 (clear watery stools). The AI model for stool state evaluation (grades 1-3) was constructed and internally verified using the cross-validation method. Second, a prospective study was conducted on the quality of CS using the app in our hospital. The primary end-point was the proportion of patients who achieved Boston Bowel Preparation Scale (BBPS) ≥6 among those who successfully used the app., Results: The AI model showed mean accuracy rates of 90.2%, 65.0%, and 89.3 for grades 1, 2, and 3, respectively. The prospective study enrolled 106 patients and revealed that 99.0% (95% confidence interval 95.3-99.9%) of patients achieved a BBPS ≥6., Conclusion: The proportion of patients with BBPS ≥6 during CS using the developed app exceeded the set expected value. This app could contribute to the performance of high-quality CS in clinical practice., (© 2024 Japan Gastroenterological Endoscopy Society.)

In submucosal invasive adenocarcinoma of the esophagogastric junction (pT1b-SM AEG), the extent of tumor submucosal (SM) invasion is measured using the vertical depth of SM invasion with the muscularis mucosa. This study aimed to investigate whether tumor thickness and depth of invasion without accounting for muscularis mucosa were superior to the vertical depth of SM invasion as metastasis predictors. We enrolled patients with pT1b-SM AEG who underwent endoscopic resection or surgical resection (SR) at our institution between January 2011 and September 2019 and were followed up for ≥2 years. The relationship between metastasis and clinicopathological factors was examined. Metastasis was defined as pathologically confirmed lymph node metastasis in the surgical specimen or recurrence during follow-up. This study included 57 patients (44 men; median age, 72 years). Endoscopic resection and SR were performed in 16 and 41 patients, respectively. Nine patients were diagnosed with metastasis: five who underwent SR showed pathologically confirmed lymph node metastasis in the surgical specimens, and four experienced recurrences during a median follow-up of 48 months. Univariate analyses showed that tumor thickness was significantly associated with metastasis (P = 0.021), and the vertical depth of SM invasion (P = 0.48) and depth of invasion (P = 0.38) were not. Furthermore, in multivariate analysis, tumor thickness ≥2800 μm (odds ratio, 38.70; P = 0.013) was a significant predictor for metastasis. Tumor thickness may be a more convenient and useful predictor of metastasis in patients with pT1b-SM AEG than the vertical depth of SM invasion., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Few reports have detailed improvements in the quality of colonoscopies with continuous training post-fellowship completion. We examined the changes in colonoscopy performance among trainees during our advanced endoscopy training program., Methods: Screening or surveillance colonoscopies performed by 11 trainees who participated in our 3-year advanced endoscopy training program between April 2015 and March 2020 were retrospectively analyzed. Quality and efficiency metrics of colonoscopies were evaluated annually., Results: Altogether, 297, 385, and 438 colonoscopies were enrolled in the first, second, and third training years, respectively. The mean insertion times were 8.6, 7.6, and 6.9 min in the first, second, and third training years, respectively, with significant improvement from the first to second year ( p = 0.03) and from the first to third year ( p < 0.01). The adenoma detection rate, proximal adenoma detection rate, and mean number of adenomas per patient exhibited a tendency to improve annually; however, the difference was not significant. Polypectomy efficiency was 10.5%, 11.2%, and 13.0%, with significant improvements from the first to third year ( p < 0.01) and from the second to third year ( p = 0.02). Insertion time and polypectomy efficiency showed significant improvements, especially among trainees experienced with <500 colonoscopies., Conclusions: Through our advanced endoscopy training program, there has been an improvement in the quality and efficiency of colonoscopy for trainees who have completed their fellowships, particularly those with <500 colonoscopies., Competing Interests: Author Hiroaki Ikematsu is an associate editor of DEN Open. The other authors declare no conflict of interest., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Introduction: The early detection of gastric neoplasms (GNs) leads to favorable treatment outcomes. The latest endoscopic system, EVIS X1, includes third-generation narrow-band imaging (3G-NBI), texture and color enhancement imaging (TXI), and high-definition white-light imaging (WLI). Therefore, this randomized phase II trial aimed to identify the most promising imaging modality for GN detection using 3G-NBI and TXI., Methods: Patients with scheduled surveillance endoscopy after a history of esophageal cancer or GN or preoperative endoscopy for known esophageal cancer or GN were randomly assigned to the 3G-NBI, TXI, or WLI groups. Endoscopic observations were performed to detect new GN lesions, and all suspected lesions were biopsied. The primary endpoint was the GN detection rate during primary observation. Secondary endpoints were the rate of missed GNs, early gastric cancer detection rate, and positive predictive value for a GN diagnosis. The decision rule had a higher GN detection rate between 3G-NBI and TXI, outperforming WLI by >1.0%., Results: Finally, 901 patients were enrolled and assigned to the 3G-NBI, TXI, and WLI groups (300, 300, and 301 patients, respectively). GN detection rates in the 3G-NBI, TXI, and WLI groups were 7.3, 5.0, and 5.6%, respectively. The rates of missed GNs were 1.0, 0.7, and 1.0%, the detection rates of early gastric cancer were 5.7, 4.0, and 5.6%, and the positive predictive values for the diagnosis of GN were 36.5, 21.3, and 36.8% in the 3G-NBI, TXI, and WLI groups, respectively., Discussion: Compared with TXI and WLI, 3G-NBI is a more promising modality for GN detection., (Copyright © 2024 by The American College of Gastroenterology.)