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Background: This study validates MRI-based tumor habitats in predicting time-to-progression (TTP), overall survival (OS), and progression site in isocitrate dehydrogenase (IDH)-wildtype glioblastoma patients., Methods: Seventy-nine patients were prospectively enrolled between January 2020 and June 2022. MRI, including diffusion-weighted and dynamic susceptibility contrast imaging, were obtained immediately post-operation and at three serial timepoints. Voxels from cerebral blood volume and apparent diffusion coefficient maps were grouped into three habitats (hypervascular cellular, hypovascular cellular, and nonviable tissue) using k-means clustering. Pre-defined cutoffs for increases in hypervascular and hypovascular cellular habitat were applied to calculate the habitat risk score. Associations between spatiotemporal habitats, habitat risk score, TTP, and OS were investigated using Cox proportional hazards modeling. Habitat risk score was compared to tumor volume using time-dependent receiver operating characteristics analysis. Progression sites were matched with spatial habitats., Results: Increases in hypervascular and hypovascular cellular habitats and habitat risk scores were associated with shorter TTP and OS (all p < .05). Hypovascular cellular habitat and habitat risk scores 1 and 2 independently predicted TTP (hazard ratio [HR], 4.14; p=.03, HR, 4.51; p=.001 and HR, 10.02; p<.001, respectively). Hypovascular cellular habitat and habitat risk score 2 independently predicted OS (HR, 4.01, p=.003; and HR, 3.27, p<.001, respectively). Habitat risk score outperformed tumor volume in predicting TTP (12-month AUC, 0.762 vs. 0.646, p=.048). Hypovascular cellular habitat predicted progression sites (mean Dice index: 0.31)., Conclusions: Multiparametric physiologic MRI-based spatiotemporal tumor habitats and habitat risk scores are useful biomarkers for early tumor progression and outcomes in IDH-wildtype glioblastoma patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Abnormal posture is known to affect the efficacy of exercise therapy for musculoskeletal diseases. However, no studies to date have examined the effect of exercise programs should take into account the posture of the upper body in patients with rotator cuff disease. This study aimed to assess how rotator cuff and corrective exercises impact shoulder function and muscle strength post-arthroscopic rotator cuff repair surgery, providing tailored rehabilitation programs for patients with forward posture., Methods: Ninety male patients who underwent arthroscopic rotator cuff repair participated in this study. The patients were randomly divided into three groups corrective exercise group (CEG, n = 29), rotator cuff exercise group (REG, n = 27), and control group (CG, n = 28). Each group was instructed to apply different exercise programs to correct posture and enhance rotator cuff strength. All patients were checked by the American Shoulder and Elbow Surgeons (ASES) score, Constant score and muscle strength, and range of motion preoperatively and postoperatively at 6 months and 1 year., Results: ASES shoulder function scores showed significant difference between the three groups (p = 0.002, F = 7.03), indicating that the corrective exercise program was more beneficial than rotator cuff exercises (p = 0.009, F = 3.78). A significant intergroup difference in mean Constant score was also noted (p = 0.025, F = 3.86), while a statistically significant interaction between time and group was observed (p = 0.032, F = 2.96)., Conclusions: These results suggested that a corrective exercise program can improve shoulder muscle strength and function after rotator cuff repair in male patients with a forward shoulder posture., (© 2024. The Author(s).)

We investigated the clinical and radiologic predictors of unruptured symptomatic intracranial artery dissection (IAD) outcomes. Unruptured symptomatic IAD patients who underwent vessel wall magnetic resonance imaging (VW-MRI) and time-of-flight magnetic resonance angiography (TOF-MRA) within 1 month after symptom onset, followed for over 12 months were included. Baseline features predicting the clinical outcome of recurrent symptoms and radiologic outcomes of aneurysmal dilatation and occlusion were analyzed using logistic regression analysis. The Kaplan-Meier method calculated the median time to morphological stability. Patients with aneurysmal dilatation were categorized into progressive and non-progressive enlargement subgroups. Seventy-three IADs from 65 patients were included. All patients showed benign clinical course (mRS 0-1). No baseline features were predictive of recurrent symptoms. Aneurysmal dilatation was associated with increased outer diameter in baseline VW-MRI (OR, 23.15; 95% CI, 3.78-141.75, P < 0.001) and TOF-MRA (OR, 10.81; 95% CI, 2.16-53.99, P = 0.004). Occlusion was inversely associated with preserved patency in baseline VW-MRI (OR, 0.1; 95% CI, 0.01-0.74, P = 0.024) and TOF-MRA (OR, 0.14; 95% CI, 0.02-0.98; P = 0.048). The median time to morphological stability was 3.9 months (95% CI, 3.16-5.5). While baseline features did not significantly differ between aneurysmal dilatation subgroups, follow-up imaging revealed significant differences in remodeling index, normalized wall index, relative signal intensity of intramural hematoma, and presence of onion-skin appearance and intramural hematoma (all P < 0.05). Our findings suggest that while unruptured IAD presents a benign clinical outcome, follow-up imaging may be necessary to monitor the progressive enlargement of aneurysmal dilatation., (© 2024. The Author(s).)

Background: Physiologic MRI-based tumor habitat analysis has the potential to predict patient outcomes by identifying the spatiotemporal habitats of glioblastoma. This study aims to prospectively validate the cut-off for tumor progression obtained from tumor habitat analysis based on physiologic MRI in ascertaining time-to-progression (TTP) and the site of progression in glioblastoma patients following concurrent chemoradiotherapy (CCRT)., Methods: In this prospective study (ClinicalTrials.gov ID: NCT02613988), we will recruit patients with IDH-wild type glioblastoma who underwent CCRT and obtained immediate post-operative and three serial post-CCRT MRI scans within a three-month interval, conducted using diffusion-weighted imaging and dynamic susceptibility contrast imaging. Voxels from cerebral blood volume and apparent diffusion coefficient maps will be grouped using k-means clustering into three spatial habitats (hypervascular cellular, hypovascular cellular, and nonviable tissue). The spatiotemporal habitats of the tumor will be evaluated by comparing changes in each habitat between the serial MRI scans (post-operative and post-CCRT #1, #2, and #3). Associations between spatiotemporal habitats and TTP will be analyzed using cox proportional hazard modeling. The site of progression will be matched with spatiotemporal habitats., Discussion: The perfusion- and diffusion-derived tumor habitat in glioblastoma is expected to stratify TTP and may serve as an early predictor for tumor progression in patients with IDH wild-type glioblastoma., Trial Registration: ClinicalTrials.gov ID: NCT02613988., (© 2024. The Author(s).)

For patients with locally advanced/metastatic urothelial carcinoma (la/mUC), first-line (1L) treatment with platinum-based chemotherapy (PBC) followed by avelumab 1L maintenance (1LM) is a recommended therapy per treatment guidelines in patients without disease progression. However, contemporary real-world (rw) data among patients receiving this treatment are necessary to understand clinical outcomes and optimal treatment sequencing. This retrospective cohort study analyzed rw treatment patterns and clinical outcomes, including overall survival (rwOS) and progression-free survival (rwPFS), in patients with la/mUC receiving avelumab 1LM. From the Flatiron Health database, 214 patients who received avelumab 1LM following 1L PBC were included. From the start of avelumab 1LM, median rwOS was 23.8 months (95% CI: 18.2-not estimable [NE]) and median rwPFS was 5.1 months (95% CI: 4.1-7.0). A total of 96 patients received second-line (2L) therapy, with 53 receiving enfortumab vedotin (EV). From the start of 2L EV, median rwOS was 11.2 months (95% CI: 6.8-NE) and median rwPFS was 4.9 months (95% CI: 3.9-8.8). Treatment patterns and clinical outcomes in this study align with guidelines and outcomes observed in the JAVELIN Bladder 100 and EV-301 clinical trials and other rw studies, supporting the use of 1L PBC followed by avelumab 1LM and 2L EV for eligible patients.

Background: We aimed to investigate the radiation dose to the eye lens (lens dose) during cerebral angiography and to evaluate the effectiveness of the lens dose reduction protocol for 3-dimensional rotational angiography (3D-RA) in reducing overall lens dose exposure., Methods: We conducted a randomized, controlled clinical trial at a tertiary hospital with patients undergoing cerebral angiography. The lens dose reduction protocol in 3D-RA involved raising the table to position the patient's eye lens away from the rotation axis. The lens dose was estimated by measuring the entrance surface air kerma using a photoluminescent glass dosimeter. The lens doses of 3D-RA, overall examination, and image quality were analyzed and compared between the two groups., Results: A total of 20 participants (mean age, 58±9.4 years; including 12 men [60%]) were enrolled and randomly assigned to either the conventional group or the dose reduction group. The median lens dose in 3D-RA was significantly lower in the dose reduction group compared with the conventional group (1.1 mGy vs 4.5 mGy, p<0.001). The total dose was significantly lower in the dose reduction group (median of 7.5 mGy vs 10.2 mGy, p=0.003). In the conventional group, 3D-RA accounted for 46% of the total lens dose, while in the dose reduction group, its proportion decreased to 16%. No significant differences were observed in the image quality between the groups., Conclusion: The lens dose reduction protocol resulted in a significant reduction in the lens dose of the 3D-RA as well as entire cerebral angiography, while maintaining the image quality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

KIF2C/MCAK (KIF2C) is the most well-characterized member of the kinesin-13 family, which is critical in the regulation of microtubule (MT) dynamics during mitosis, as well as interphase. This systematic review briefly describes the important structural elements of KIF2C, its regulation by multiple molecular mechanisms, and its broad cellular functions. Furthermore, it systematically summarizes its oncogenic potential in malignant progression and performs a meta-analysis of its prognostic value in cancer patients. KIF2C was shown to be involved in multiple crucial cellular processes including cell migration and invasion, DNA repair, senescence induction and immune modulation, which are all known to be critical during the development of malignant tumors. Indeed, an increasing number of publications indicate that KIF2C is aberrantly expressed in multiple cancer entities. Consequently, we have highlighted its involvement in at least five hallmarks of cancer, namely: genome instability, resisting cell death, activating invasion and metastasis, avoiding immune destruction and cellular senescence. This was followed by a systematic search of KIF2C/MCAK's expression in various malignant tumor entities and its correlation with clinicopathologic features. Available data were pooled into multiple weighted meta-analyses for the correlation between KIF2C high protein or gene expression and the overall survival in breast cancer, non-small cell lung cancer and hepatocellular carcinoma patients. Furthermore, high expression of KIF2C was correlated to disease-free survival of hepatocellular carcinoma. All meta-analyses showed poor prognosis for cancer patients with KIF2C high expression, associated with a decreased overall survival and reduced disease-free survival, indicating KIF2C's oncogenic potential in malignant progression and as a prognostic marker. This work delineated the promising research perspective of KIF2C with modern in vivo and in vitro technologies to further decipher the function of KIF2C in malignant tumor development and progression. This might help to establish KIF2C as a biomarker for the diagnosis or evaluation of at least three cancer entities.

Background: The standard of care for patients with intermediate-to-high risk renal cell carcinoma is partial or radical nephrectomy followed by surveillance. We aimed to investigate use of nivolumab before nephrectomy followed by adjuvant nivolumab in patients with high-risk renal cell carcinoma to determine recurrence-free survival compared with surgery only., Methods: In this open-label, randomised, phase 3 trial (PROSPER EA8143), patients were recruited from 183 community and academic sites across the USA and Canada. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1, with previously untreated clinical stage T2 or greater or T any N+ renal cell carcinoma of clear cell or non-clear cell histology planned for partial or radical nephrectomy. Selected patients with oligometastatic disease, who were disease free at other disease sites within 12 weeks of surgery, were eligible for inclusion. We randomly assigned (1:1) patients using permuted blocks (block size of 4) within stratum (clinical TNM stage) to either nivolumab plus surgery, or surgery only followed by surveillance. In the nivolumab group, nivolumab 480 mg was administered before surgery, followed by nine adjuvant doses. The primary endpoint was investigator-reviewed recurrence-free survival in patients with renal cell carcinoma assessed in all randomly assigned patients regardless of histology. Safety was assessed in all randomly assigned patients who started the assigned protocol treatment. This trial is registered with ClinicalTrials.gov, NCT03055013, and is closed to accrual., Findings: Between Feb 2, 2017, and June 2, 2021, 819 patients were randomly assigned to nivolumab plus surgery (404 [49%]) or surgery only (415 [51%]). 366 (91%) of 404 patients assigned to nivolumab plus surgery and 387 (93%) of 415 patients assigned to surgery only group started treatment. Median age was 61 years (IQR 53-69), 248 (30%) of 819 patients were female, 571 (70%) were male, 672 (88%) were White, and 77 (10%) were Hispanic or Latino. The Data and Safety Monitoring Committee stopped the trial at a planned interim analysis (March 25, 2022) because of futility. Median follow-up was 30·4 months (IQR 21·5-42·4) in the nivolumab group and 30·1 months (21·9-41·8) in the surgery only group. 381 (94%) of 404 patients in the nivolumab plus surgery group and 399 (96%) of 415 in the surgery only group had renal cell carcinoma and were included in the recurrence-free survival analysis. As of data cutoff (May 24, 2023), recurrence-free survival was not significantly different between nivolumab (125 [33%] of 381 had recurrence-free survival events) versus surgery only (133 [33%] of 399; hazard ratio 0·94 [95% CI 0·74-1·21]; one-sided p=0·32). The most common treatment-related grade 3-4 adverse events were elevated lipase (17 [5%] of 366 patients in the nivolumab plus surgery group vs none in the surgery only group), anaemia (seven [2%] vs nine [2%]), increased alanine aminotransferase (ten [3%] vs one [<1%]), abdominal pain (four [1%] vs six [2%]), and increased serum amylase (nine [2%] vs none). 177 (48%) patients in the nivolumab plus surgery group and 93 (24%) in the surgery only group had grade 3-5 adverse events due to any cause, the most common of which were anaemia (23 [6%] vs 19 [5%]), hypertension (27 [7%] vs nine [2%]), and elevated lipase (18 [5%] vs six [2%]). 48 (12%) of 404 patients in the nivolumab group and 40 (10%) of 415 in the surgery only group died, of which eight (2%) and three (1%), respectively, were determined to be treatment-related., Interpretation: Perioperative nivolumab before nephrectomy followed by adjuvant nivolumab did not improve recurrence-free survival versus surgery only followed by surveillance in patients with high-risk renal cell carcinoma., Funding: US National Institutes of Health National Cancer Institute and Bristol Myers Squibb., Competing Interests: Declaration of interests VM reports support for attending meetings or travel from American College of Surgeons; and participation on the Advisory Board on Diversity, Equity, and Inclusion at Exelixis. VM also reports a leadership role (unpaid) on Society of Urologic Oncology Clinical Trials Consortia. DFM received payment or honoraria from Bristol Myers Squibb, Pfizer, Merck, Eisai, Xilio, Aveo, Genentech, Cullinan, and Exelixis; and support for attending meetings or travel from Bristol Myers Squibb, Merck, Genentech, Pfizer, Exelixis, X4 Pharma, and Alkermes. LCH reports ownership of stock in Coherus and previous employment at Surface Oncology. SS reports grants or contracts from Bristol Myers Squibb and Exelixis to their institution; and royalties or licenses from Biogenex. SS also reports consulting fees from AstraZeneca, Merck, and CRISPR Therapeutics; and a leadership or fiduciary role at American Association for Cancer Research as Senior Editor at Clinical Cancer Research and at the NCI National Cancer Institute as Renal Task Force Co-Chair. HE reports consulting fees for Janssen and Aveo advisory boards. NA reports grants or contracts from Exelixis, Genentech, Merck, and Bristol Myers Squibb; and consulting fees from Exelixis, Bristol Myers Squibb, Aveo, Merck, EMD Serono, and Sanofi. MAB reports institutional grants from Merck, Xencor, Bayer, Bristol Myers Squibb, Genentech/Roche, SeaGen, Incyte, Nektar, AstraZeneca, Tricon Pharmaceuticals, Genome & Company, AAA, Peloton Therapeutics, and Pfizer; and payment or honoraria for Advisory Board participation from Exelixis, Bayer, Bristol Myers Squibb, Eisai, Pfizer, AstraZeneca, Janssen, Calithera Biosciences, Genomic Health, Nektar, EMD Serono, SeaGen, and Sanofi. TMM reports payment to their institution for clinical trials from Merck, Curium, and ECOG; consulting fees from Impact Network and Aptitude Health; and honoraria from Exelixis and Blue Earth Diagnostics. TC reports support from Alkermes, AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers Squibb, Calithera, Circle Pharma, Deciphera Pharmaceuticals, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, Gilead, HiberCell, IQVIA, Infinity, Ipsen, Jansen, Kanaph, Lilly, Merck, Nikang, Neomorph, Nuscan/PrecedeBio, Novartis, Oncohost, Pfizer, Roche, Sanofi/Aventis, Scholar Rock, Surface Oncology, Takeda, Tempest, Up-To-Date, and CME events (Peerview, OncLive, MJH, CCO, and others), outside the submitted work. TC also reports institutional research funding related to clinical trials from AstraZeneca, Aveo, Arcus, Bayer, Bristol Myers Squibb, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, Lilly, Merck, Nikang, Novartis, Pfizer, Roche, Sanofi/Aventis, and Takeda. TC also reports consulting fees from Alkermes, AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers Squibb, Calithera, Circle Pharma, Deciphera Pharmaceuticals, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, Gilead, HiberCell, IQVIA, Infinity, Ipsen, Jansen, Kanaph, Lilly, Merck, Nikang, Neomorph, Nuscan/PrecedeBio, Novartis, Oncohost, Pfizer, Roche, Sanofi/Aventis, Scholar Rock, Surface Oncology, Takeda, Tempest, Up-To-Date, CME events (Peerview, OncLive, MJH, CCO, and others), outside the submitted work. TC also reports payment or honoraria from Alkermes, AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers Squibb, Calithera, Circle Pharma, Deciphera Pharmaceuticals, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, Gilead, HiberCell, IQVIA, Infinity, Ipsen, Jansen, Kanaph, Lilly, Merck, Nikang, Neomorph, Nuscan/PrecedeBio, Novartis, Oncohost, Pfizer, Roche, Sanofi/Aventis, Scholar Rock, Surface Oncology, Takeda, Tempest, Up-To-Date, CME events (Peerview, OncLive, MJH, CCO, and others), outside the submitted work. TC also reports support for attending meetings or travel in relation to meetings, lectures, and advisory boards; and participates in the Aravive Data and Safety Monitoring Board or advisory board. TC also reports a patent related to ctDNA and biomarkers of response to immune checkpoint inhibitors (no royalties as of current date). TC also reports a leadership or fiduciary role in KidneyCan (unpaid) and committees for American Society of Clinical Oncology, European Society of Medical Oncology, National Comprehensive Cancer Network, and Genitourinary Steering Committee of the NCI. TC also reports stock ownership (for being an advisor) of Pionyr, Tempest, Precede Bio, Osel, Curesponse, Immdura, and Primium. TC also reports no receipt of equipment, materials, drugs, medical writing, gifts, or other services, except for travel and accommodation (flights, hotel, and meals) related to advisory or consulting when travel needed. TC also reports to be supported in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE(2P50CA101942-16) and Program 5P30CA006516-56, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, Pan-Mass Challenge, Hinda and Arthur Marcus Fund, and Loker Pinard Funds for Kidney Cancer Research at Dana Farber Cancer Institute. MDD reports participation on the Scientific Advisory Boards (honoraria received) at Merck, Eisai, Exelixis, and Janssen. DYH reports compensation from consulting work from Bristol Myers Squibb, Merck, Ipsen, Exelixis, Pfizer, and Eisai. BS reports consulting fees from Merck, Veracyte, Telix, and Johnson and Johnson; payment or honoraria from Merck; and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Telix. BCL reports a leadership or fiduciary role at Kidney Cancer Association as Chair of Board of Directors. JM reports participation on the NCI Central Institutional Review Board and has been recused from all discussions of this study. RU reports participation and financial support on a Data Safety Monitoring Board at Pfizer and other financial support on a steering committee at Merck. RU also reports a leadership or fiduciary role (non-financial support) at Haymarket Media as a board member. GB reports a leadership role during the study as President of the Society of Urologic Oncology–Clinical Trial Consortium. NBH reports participation in the Data and Safety Monitoring Committee atezolizumab at Roche Genentech and advisory boards at Bristol Myers Squibb and Eisai. NBH also reports a non-financial leadership role as ECOG ACRIN Genitourinary Committee Co-Chair. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

The treatment landscape for patients with advanced urothelial carcinoma continues to evolve. Enfortumab vedotin plus pembrolizumab has received Food and Drug Administration approval based on recent phase 3 trial data showing superior efficacy compared with first-line platinum-based chemotherapy; however, its distinct toxicity profile may make it less suitable for some patients, and availability in some countries may be limited by cost considerations. Consequently, platinum-based chemotherapy is expected to remain an important first-line treatment option. Choice of platinum regimen (cisplatin- or carboplatin-based) is informed by assessment of clinical characteristics, including performance status, kidney function, and presence of peripheral neuropathy or heart failure. For patients without disease progression after completing platinum-based chemotherapy, avelumab first-line maintenance treatment is recommended by international guidelines. For patients who have disease progression, pembrolizumab is the preferred approach. Additionally, following results from a recent phase 3 trial, nivolumab plus cisplatin-based chemotherapy has also received Food and Drug Administration approval and is an additional first-line treatment option for cisplatin-eligible patients. Later-line options for patients with advanced urothelial carcinoma, depending on prior treatment, may include enfortumab vedotin, erdafitinib (for patients with FGFR2/3 mutations or fusions/rearrangements), sacituzumab govitecan, and platinum rechallenge. For the small proportion of patients ineligible for any platinum-based chemotherapy (i.e., unsuitable for cisplatin or carboplatin), immune checkpoint inhibitor monotherapy with pembrolizumab or atezolizumab is a first-line treatment option, although approved agents vary between countries. In summary, this podcast discusses recent developments in the treatment landscape for advanced urothelial carcinoma, eligibility for platinum-based chemotherapy, potential first-line treatment options, and treatment sequencing. Supplementary file1 (MP4 246907 KB)., (© 2024. The Author(s).)

Background: The aim of this study is to investigate the perioperative composite textbook outcomes of pancreatic surgery after minimally invasive pancreatoduodenectomy (MIPD)., Materials and Methods: The cohort study was conducted across 10 institutions and included 1552 patients who underwent MIPD registered with the Korean Study Group on Minimally Invasive Pancreatic Surgery between May 2007 and April 2020. We analyzed perioperative textbook outcomes of pancreatic surgery after MIPD. Subgroup analyses were performed to assess outcomes based on the hospital volume of MIPD., Results: Among all patients, 21.8% underwent robotic pancreatoduodenectomy. High-volume centers (performing >20 MIPD/year) performed 88.1% of the procedures. The incidence of clinically relevant postoperative pancreatic fistula was 11.5%. Severe complications (Clavien-Dindo grade ≥IIIa) occurred in 15.1% of the cases. The 90-day mortality rate was 0.8%. The mean hospital stay was 13.7 days. Textbook outcomes of pancreatic surgery success were achieved in 60.4% of patients, with higher rates observed in high-volume centers than in low-volume centers (62.2% vs. 44.7%, P <0.001). High-volume centers exhibited significantly lower conversion rates (5.4% vs. 12.5%, P =0.001), lower 90-day mortality (0.5% vs. 2.7%, P =0.001), and lower 90-day readmission rates (4.5% vs. 9.6%, P =0.006) than those low-volume centers., Conclusion: MIPD could be performed safely with permissible perioperative outcomes, including textbook outcomes of pancreatic surgery, particularly in experienced centers. The findings of this study provided valuable insights for guiding surgical treatment decisions in periampullary disease., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: This study evaluated whether generative artificial intelligence (AI)-based augmentation (GAA) can provide diverse and realistic imaging phenotypes and improve deep learning-based classification of isocitrate dehydrogenase (IDH) type in glioma compared with neuroradiologists., Methods: For model development, 565 patients (346 IDH-wildtype, 219 IDH-mutant) with paired contrast-enhanced T1 and FLAIR MRI scans were collected from tertiary hospitals and The Cancer Imaging Archive. Performance was tested on internal (119, 78 IDH-wildtype, 41 IDH-mutant [IDH1 and 2]) and external test sets (108, 72 IDH-wildtype, 36 IDH-mutant). GAA was developed using a score-based diffusion model and ResNet50 classifier. The optimal GAA was selected in comparison with the null model. Two neuroradiologists (R1, R2) assessed realism, diversity of imaging phenotypes, and predicted IDH mutation. The performance of a classifier trained with optimal GAA was compared with that of neuroradiologists using the area under the receiver operating characteristics curve (AUC). The effect of tumor size and contrast enhancement on GAA performance was tested., Results: Generated images demonstrated realism (Turing's test: 47.5-50.5%) and diversity indicating IDH type. Optimal GAA was achieved with augmentation with 110 000 generated slices (AUC: 0.938). The classifier trained with optimal GAA demonstrated significantly higher AUC values than neuroradiologists in both the internal (R1, P = .003; R2, P < .001) and external test sets (R1, P < .01; R2, P < .001). GAA with large-sized tumors or predominant enhancement showed comparable performance to optimal GAA (internal test: AUC 0.956 and 0.922; external test: 0.810 and 0.749)., Conclusions: The application of generative AI with realistic and diverse images provided better diagnostic performance than neuroradiologists for predicting IDH type in glioma., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Differentiating intracranial aneurysms from normal variants using CT angiography (CTA) or MR angiography (MRA) poses significant challenges. This study aimed to evaluate the efficacy of proton-density MRA (PD-MRA) compared to high-resolution time-of-flight MRA (HR-MRA) in diagnosing aneurysms among patients with indeterminate findings on conventional CTA or MRA., Materials and Methods: In this retrospective analysis, we included patients who underwent both PD-MRA and HR-MRA from August 2020 to July 2022 to assess lesions deemed indeterminate on prior conventional CTA or MRA examinations. Three experienced neuroradiologists independently reviewed the lesions using HR-MRA and PD-MRA with reconstructed voxel sizes of 0.25 3 mm 3 or 0.2 3 mm 3 , respectively. A neurointerventionist established the gold standard with digital subtraction angiography. We compared the performance of HR-MRA, PD-MRA (0.25 3 -mm 3 voxel), and PD-MRA (0.2 3 -mm 3 voxel) in diagnosing aneurysms, both per lesion and per patient. The Fleiss kappa statistic was used to calculate inter-reader agreement., Results: The study involved 109 patients (average age 57.4 ± 11.0 years; male:female ratio, 11:98) with 141 indeterminate lesions. Of these, 78 lesions (55.3%) in 69 patients were confirmed as aneurysms by the reference standard. PD-MRA (0.25 3 -mm 3 voxel) exhibited significantly higher per-lesion diagnostic performance compared to HR-MRA across all three readers: sensitivity ranged from 87.2%-91.0% versus 66.7%-70.5%; specificity from 93.7%-96.8% versus 58.7%-68.3%; and accuracy from 90.8%-92.9% versus 63.8%-69.5% ( P ≤ 0.003). Furthermore, PD-MRA (0.25 3 -mm 3 voxel) demonstrated significantly superior per-patient specificity and accuracy compared to HR-MRA across all evaluators ( P ≤ 0.013). The diagnostic accuracy of PD-MRA (0.2 3 -mm 3 voxel) surpassed that of HR-MRA and was comparable to PD-MRA (0.25 3 -mm 3 voxel). The kappa values for inter-reader agreements were significantly higher in PD-MRA (0.820-0.938) than in HR-MRA (0.447-0.510)., Conclusion: PD-MRA outperformed HR-MRA in diagnostic accuracy and demonstrated almost perfect inter-reader consistency in identifying intracranial aneurysms among patients with lesions initially indeterminate on CTA or MRA., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 The Korean Society of Radiology.)

Importance: Ethanol ablation (EA) was shown to be safe and effective for treating ranula, but few studies have assessed long-term outcomes and recurrence of ranula after EA., Objective: To evaluate the long-term outcomes and the risk factors for recurrence and receipt of subsequent surgery in patients who underwent treatment with EA for ranula., Design, Setting, and Participants: This case-series study was conducted at a single tertiary hospital and assessed patients who were treated with EA between July 2009 and March 2021. Among 70 consecutive patients, those with follow-up loss or who were followed up for less than 24 months were excluded., Exposures: EA for ranula., Main Outcomes and Measures: The primary outcome was recurrence at last follow-up after single or multiple EA sessions. Secondary outcomes included receipt of subsequent surgery and the recurrence-free survival (RFS) rate after initial EA. Factors possibly associated with outcomes included patient age and sex; ranula site, type, diameter, volume, and echogenicity; the presentation-to-EA interval; parapharyngeal space extension; and sublingual gland herniation. Risk factors were identified on logistic regression analyses. Two-year RFS rates were analyzed for the initial cohort using the Kaplan-Meier method and compared by log-rank tests., Results: A total of 57 patients (mean [SD] age, 26.4 [12.1] years; 24 female individuals [42%]) who were followed up for a median of 57 months (range, 24-167 months) were included. The recurrence rate was 33% (n = 19), and 11 (19%) underwent subsequent surgery. Among patients with recurrence, 86% (31 of 36) experienced first recurrence within 12 months after initial EA. A presentation-to-EA interval of 12 months or longer was associated with an increased risk of recurrence (adjusted odds ratio [OR], 3.74; 95% CI, 1.01-13.82). No risk factors were significantly associated with subsequent surgery (highest OR in parapharyngeal space extension: adjusted OR, 4.96; 95% CI, 0.94-26.35). Among the initial cohort of 70 patients, 2-year RFS was lower in a maximum diameter of ranula of 5 cm or greater than less than 5 cm (24% [95% CI, 7%-41%] vs 50% [95% CI, 34%-66%]; difference, 26% [95% CI, -4% to 56%]; log-rank test, P = .02)., Conclusions and Relevance: This case-series study found that the recurrence rate of ranula after EA was 33%. A presentation-to-EA interval of 12 months or longer may be a risk factor for recurrence, suggesting that early intervention with EA might minimize recurrence. Most first recurrences occurred within 12 months after EA, with a maximum diameter of ranula of 5 cm or greater being a possible risk factor.

In general, it is difficult to visualize internal ocular structure and detect a lesion such as a cataract or glaucoma using the current ultrasound brightness-mode (B-mode) imaging. This is because the internal structure of the eye is rich in moisture, resulting in a lack of contrast between tissues in the B-mode image, and the penetration depth is low due to the attenuation of the ultrasound wave. In this study, the entire internal ocular structure of a bovine eye was visualized in an ex vivo environment using the compound acoustic radiation force impulse (CARFI) imaging scheme based on the phase-inverted ultrasound transducer (PIUT). In the proposed method, the aperture of the PIUT is divided into four sections, and the PIUT is driven by the out-of-phase input signal capable of generating split-focusing at the same time. Subsequently, the compound imaging technique was employed to increase signal-to-noise ratio (SNR) and to reduce displacement error. The experimental results demonstrated that the proposed technique could provide an acoustic radiation force impulse (ARFI) image of the bovine eye with a broader depth-of-field (DOF) and about 80% increased SNR compared to the conventional ARFI image obtained using the in-phase input signal. Therefore, the proposed technique can be one of the useful techniques capable of providing the image of the entire ocular structure to diagnose various eye diseases.

Purpose: Locally advanced/metastatic urothelial cancer (la/mUC) affects patients' quality of life (QOL) and functioning. We describe the impact of first-line (1L) enfortumab vedotin (EV) alone or with pembrolizumab (P) on QOL/functioning/symptoms in patients with la/mUC who were cisplatin-ineligible from EV-103 Cohort K., Methods: In this phase Ib/II trial, patients were randomly assigned 1:1 to EV + P or EV monotherapy (mono). Exploratory patient-reported outcomes (PROs) were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire (EORTC QLQ-C30) and Brief Pain Inventory Short Form (BPI-SF) at baseline, once per week for cycles 1-3, and then in every cycle through the end of treatment. Changes in scores from baseline to week 24, reported as least squares mean (standard error), were assessed by mixed models for repeated measures. There were no formal statistical comparisons between treatment arms., Results: Of 149 patients treated, 65 (EV + P) and 63 (EV mono) comprised the PRO analysis set. For EV + P, EORTC QLQ-C30 QOL was maintained through week 24 with improvements in emotional functioning, pain, and insomnia. Clinically meaningful improvements were seen in EORTC QLQ-C30 pain after EV + P at weeks 12 (-14.41 [3.14]) and 24 (-14.99 [3.56]) and BPI-SF worst pain at week 24 (-2.07 [0.37]). For EV mono, EORTC QLQ-C30 QOL remained stable with clinically meaningful improvements in EORTC QLQ-C30 pain (-12.55 [4.27]), insomnia (-14.46 [4.69]), and constipation (-10.09 [4.35]) at week 24. There were small-to-moderate improvements in BPI-SF worst pain at week 24., Conclusion: EV + P in patients with la/mUC who were cisplatin-ineligible was associated with preservation or improvement of QOL/functioning/symptoms. Improvement in pain was seen in both PRO instruments and treatment arms. These data complement clinical outcomes of 1L EV + P.

Backgruound: We aimed to evaluate the utility of repeat biopsy of thyroid nodules classified as atypia of undetermined significance with architectural atypia (IIIB) on core-needle biopsy (CNB)., Methods: This retrospective study evaluated patients with thyroid nodules categorized as IIIB on CNB between 2013 and 2015. Demographic characteristics, subsequent biopsy results, and ultrasound (US) images were evaluated. The malignancy rates of nodules according to number of CNBs and the number of IIIB diagnoses was compared. Demographic and US features were evaluated to determine factors predictive of malignancy., Results: Of 1,003 IIIB nodules on CNB, the final diagnosis was determined for 328 (32.7%) nodules, with 121 of them confirmed as malignant, resulting in a malignancy rate of 36.9% (95% confidence interval, 31.7% to 42.1%). Repeat CNB was performed in 248 nodules (24.7%), with 75 (30.2%), 131 (52.8%), 13 (5.2%), 26 (10.5%), one (0.4%), and two (0.8%) reclassified into categories II, IIIB, IIIA, IV, V, and VI, respectively. Malignancy rates were not significantly affected by the number of CNBs (P=0.291) or the number of IIIB diagnoses (P=0.473). None of the nodules confirmed as category II on repeat CNB was malignant. US features significantly associated with malignancy (P<0.003) included solid composition, irregular margins, microcalcifications, and high suspicion on the US risk stratification system., Conclusion: Repeat biopsy of nodules diagnosed with IIIB on CNB did not increase the detection of malignancy but can potentially reduce unnecessary surgery. Repeat biopsy should be performed selectively, with US features guiding the choice between repeat biopsy and diagnostic surgery.

(1) Background: Advancements in the field of liver surgery have led to a critical need for precise estimations of preoperative liver function to prevent post-hepatectomy liver failure (PHLF), a significant cause of morbidity and mortality. This study introduces a novel application of artificial intelligence (AI) in determining safe resection volumes according to a patient's liver function in major hepatectomies. (2) Methods: We incorporated a deep learning approach, incorporating a unique liver-specific loss function, to analyze patient characteristics, laboratory data, and liver volumetry from computed tomography scans of 52 patients. Our approach was evaluated against existing machine and deep learning techniques. (3) Results: Our approach achieved 68.8% accuracy in predicting safe resection volumes, demonstrating superior performance over traditional models. Furthermore, it significantly reduced the mean absolute error in under-predicted volumes to 23.72, indicating a more precise estimation of safe resection limits. These findings highlight the potential of integrating AI into surgical planning for liver resections. (4) Conclusion: By providing more accurate predictions of safe resection volumes, our method aims to minimize the risk of PHLF, thereby improving clinical outcomes for patients undergoing hepatectomy.

Aim: To review the imaging characteristics of granular cell tumours in the head and neck and assess their associations with pathological findings., Materials and Methods: Eleven patients (10 [91%] women, mean age 43 years) with histopathologically confirmed granular cell tumours were included in this study. Preoperative imaging studies were performed, including computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound. The location of the tumours, their imaging features, and histopathological findings were analysed., Results: Among the 11 granular cell tumours, four (36%), three (27%), and two (18%) tumours were found in the submucosal layer, subcutaneous layer, and intramuscular area, respectively. On CT, all tumours exhibited homogeneous iso-attenuating enhancement compared with adjacent muscle, and nine out of the 11 tumours (81%) demonstrated well-defined margins. On T2-weighted imaging (T2WI), four out of five tumours (80%) demonstrated iso-signal intensity compared with adjacent muscles, and four tumours (80%) exhibited homogeneous signal intensity. The apparent diffusion coefficient (ADC) values ranged from 0.68-0.81 × 10 -3 mm 2 /s. Histopathological examination revealed densely packed tumour cells with variable amounts of fibrous stroma., Conclusion: Granular cell tumours were characterised by well-defined and iso-signals on T2WI and low mean ADC values, and were predominantly located in the submucosal, subcutaneous, or intramuscular areas in middle-aged women. The characteristic locations, demographic characteristics, and imaging findings can help to differentiate granular cell tumours from other soft-tissue tumours in the head and neck., (Copyright © 2023. Published by Elsevier Ltd.)

The JAVELIN Bladder 100 phase III trial led to the incorporation of avelumab first-line (1L) maintenance treatment into international guidelines as a standard of care for patients with advanced urothelial carcinoma (UC) without progression after 1L platinum-based chemotherapy. JAVELIN Bladder 100 showed that avelumab 1L maintenance significantly prolonged overall survival (OS) and progression-free survival in this population compared with a 'watch-and-wait' approach. The aim of this manuscript is to review clinical studies of avelumab 1L maintenance in patients with advanced UC, including long-term efficacy and safety data from JAVELIN Bladder 100, subgroup analyses in clinically relevant subpopulations, and 'real-world' data obtained outside of clinical trials, providing a comprehensive resource to support patient management. Extended follow-up from JAVELIN Bladder 100 has shown that avelumab provides a long-term efficacy benefit, with a median OS of 23.8 months measured from start of maintenance treatment, and 29.7 months measured from start of 1L chemotherapy. Longer OS was observed across subgroups, including patients who received 1L cisplatin + gemcitabine, patients who received four or six cycles of 1L chemotherapy, and patients with complete response, partial response, or stable disease as best response to 1L induction chemotherapy. No new safety signals were seen in patients who received ≥1 year of avelumab treatment, and toxicity was similar in those who had received cisplatin or carboplatin with gemcitabine. Other clinical datasets, including noninterventional studies conducted in Europe, USA, and Asia, have confirmed the efficacy of avelumab 1L maintenance. Potential subsequent treatment options after avelumab maintenance include antibody-drug conjugates (enfortumab vedotin or sacituzumab govitecan), erdafitinib in biomarker-selected patients, platinum rechallenge in suitable patients, nonplatinum chemotherapy, and clinical trial participation; however, evidence to determine optimal treatment sequences is needed. Ongoing trials of avelumab-based combination regimens as maintenance treatment have the potential to evolve the treatment landscape for patients with advanced UC., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Patients with locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible for cisplatin-based therapy have limited first-line (1L) treatment options and significant need for improved therapies. Enfortumab vedotin (EV) and pembrolizumab (Pembro) individually have shown a survival benefit in urothelial cancer in second-line + la/mUC settings. Here, we present data from the pivotal trial of EV plus Pembro (EV + Pembro) in the 1L setting., Patients and Methods: In Cohort K of the EV-103 phase Ib/II study, cisplatin-ineligible patients with previously untreated la/mUC were randomly assigned 1:1 to receive EV as monotherapy or in combination with Pembro. The primary end point was confirmed objective response rate (cORR) per blinded independent central review. Secondary end points included duration of response (DOR) and safety. There were no formal statistical comparisons between treatment arms., Results: The cORR was 64.5% (95% CI, 52.7 to 75.1) and 45.2% (95% CI, 33.5 to 57.3) for patients treated with EV + Pembro (N = 76) and EV monotherapy (N = 73), respectively. The median DOR was not reached for the combination and was 13.2 months for monotherapy; 65.4% and 56.3% of patients who responded to the combination and monotherapy, respectively, maintained a response at 12 months. The most common grade 3 or higher treatment-related adverse events (TRAEs) in patients treated with the combination were maculopapular rash (17.1%), fatigue (9.2%), and neutropenia (9.2%). EV TRAEs of special interest (any grade) in the combination arm included skin reactions (67.1%) and peripheral neuropathy (60.5%)., Conclusion: EV + Pembro showed a high cORR with durable responses as 1L treatment in cisplatin-ineligible patients with la/mUC. Patients who received EV monotherapy had a response and safety profile consistent with previous studies. Adverse events for EV + Pembro were manageable, with no new safety signals observed.

Objectives: An appropriate and fast clinical referral suggestion is important for intra-axial mass-like lesions (IMLLs) in the emergency setting. We aimed to apply an interpretable deep learning (DL) system to multiparametric MRI to obtain clinical referral suggestion for IMLLs, and to validate it in the setting of nontraumatic emergency neuroradiology., Methods: A DL system was developed in 747 patients with IMLLs ranging 30 diseases who underwent pre- and post-contrast T1-weighted (T1CE), FLAIR, and diffusion-weighted imaging (DWI). A DL system that segments IMLLs, classifies tumourous conditions, and suggests clinical referral among surgery, systematic work-up, medical treatment, and conservative treatment, was developed. The system was validated in an independent cohort of 130 emergency patients, and performance in referral suggestion and tumour discrimination was compared with that of radiologists using receiver operating characteristics curve, precision-recall curve analysis, and confusion matrices. Multiparametric interpretable visualisation of high-relevance regions from layer-wise relevance propagation overlaid on contrast-enhanced T1WI and DWI was analysed., Results: The DL system provided correct referral suggestions in 94 of 130 patients (72.3%) and performed comparably to radiologists (accuracy 72.6%, McNemar test; p = .942). For distinguishing tumours from non-tumourous conditions, the DL system (AUC, 0.90 and AUPRC, 0.94) performed similarly to human readers (AUC, 0.81~0.92, and AUPRC, 0.88~0.95). Solid portions of tumours showed a high overlap of relevance, but non-tumours did not (Dice coefficient 0.77 vs. 0.33, p < .001), demonstrating the DL's decision., Conclusions: Our DL system could appropriately triage patients using multiparametric MRI and provide interpretability through multiparametric heatmaps, and may thereby aid neuroradiologic diagnoses in emergency settings., Clinical Relevance Statement: Our AI triages patients with raw MRI images to clinical referral pathways in brain intra-axial mass-like lesions. We demonstrate that the decision is based on the relative relevance between contrast-enhanced T1-weighted and diffusion-weighted images, providing explainability across multiparametric MRI data., Key Points: • A deep learning (DL) system using multiparametric MRI suggested clinical referral to patients with intra-axial mass-like lesions (IMLLs) similar to radiologists (accuracy 72.3% vs. 72.6%). • In the differentiation of tumourous and non-tumourous conditions, the DL system (AUC, 0.90) performed similar with radiologists (AUC, 0.81-0.92). • The DL's decision basis for differentiating tumours from non-tumours can be quantified using multiparametric heatmaps obtained via the layer-wise relevance propagation method., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Objective: Three-dimensional rotational angiography (3D-RA) is increasingly used for the evaluation of intracranial aneurysms (IAs); however, radiation exposure to the lens is a concern. We investigated the effect of head off-centering by adjusting table height on the lens dose during 3D-RA and its feasibility in patient examination., Materials and Methods: The effect of head off-centering during 3D-RA on the lens radiation dose at various table heights was investigated using a RANDO head phantom (Alderson Research Labs). We prospectively enrolled 20 patients (58.0 ± 9.4 years) with IAs who were scheduled to undergo bilateral 3D-RA. In all patients' 3D-RA, the lens dose-reduction protocol involving elevation of the examination table was applied to one internal carotid artery, and the conventional protocol was applied to the other. The lens dose was measured using photoluminescent glass dosimeters (GD-352M, AGC Techno Glass Co., LTD), and radiation dose metrics were compared between the two protocols. Image quality was quantitatively analyzed using source images for image noise, signal-to-noise ratio, and contrast-to-noise ratio. Additionally, three reviewers qualitatively assessed the image quality using a five-point Likert scale., Results: The phantom study showed that the lens dose was reduced by an average of 38% per 1 cm increase in table height. In the patient study, the dose-reduction protocol (elevating the table height by an average of 2.3 cm) led to an 83% reduction in the median dose from 4.65 mGy to 0.79 mGy ( P < 0.001). There were no significant differences between dose-reduction and conventional protocols in the kerma area product (7.34 vs. 7.40 Gy·cm², P = 0.892), air kerma (75.7 vs. 75.1 mGy, P = 0.872), and image quality., Conclusion: The lens radiation dose was significantly affected by table height adjustment during 3D-RA. Intentional head off-centering by elevation of the table is a simple and effective way to reduce the lens dose in clinical practice., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2023 The Korean Society of Radiology.)

Purpose: Combination programmed cell death protein 1/cytotoxic T-cell lymphocyte-4-blockade and dual BRAF/MEK inhibition have each shown significant clinical benefit in patients with BRAFV600 -mutant metastatic melanoma, leading to broad regulatory approval. Little prospective data exist to guide the choice of either initial therapy or treatment sequence in this population. This study was conducted to determine which initial treatment or treatment sequence produced the best efficacy., Patients and Methods: In a phase III trial, patients with treatment-naive BRAFV600 -mutant metastatic melanoma were randomly assigned to receive either combination nivolumab/ipilimumab (arm A) or dabrafenib/trametinib (arm B) in step 1, and at disease progression were enrolled in step 2 to receive the alternate therapy, dabrafenib/trametinib (arm C) or nivolumab/ipilimumab (arm D). The primary end point was 2-year overall survival (OS). Secondary end points were 3-year OS, objective response rate, response duration, progression-free survival, crossover feasibility, and safety., Results: A total of 265 patients were enrolled, with 73 going onto step 2 (27 in arm C and 46 in arm D). The study was stopped early by the independent Data Safety Monitoring Committee because of a clinically significant end point being achieved. The 2-year OS for those starting on arm A was 71.8% (95% CI, 62.5 to 79.1) and arm B 51.5% (95% CI, 41.7 to 60.4; log-rank P = .010). Step 1 progression-free survival favored arm A ( P = .054). Objective response rates were arm A: 46.0%; arm B: 43.0%; arm C: 47.8%; and arm D: 29.6%. Median duration of response was not reached for arm A and 12.7 months for arm B ( P < .001). Crossover occurred in 52% of patients with documented disease progression. Grade ≥ 3 toxicities occurred with similar frequency between arms, and regimen toxicity profiles were as anticipated., Conclusion: Combination nivolumab/ipilimumab followed by BRAF and MEK inhibitor therapy, if necessary, should be the preferred treatment sequence for a large majority of patients.

This study aimed to assess the effect of a combined exercise program on lower-extremity alignment and knee pain in patients with genu varum. Forty-seven middle-aged women with knee pain and genu varum were randomly divided into the exercise (EG, n = 24) and control (CG, n = 23) groups. The exercise group underwent a combined exercise program lasting 60 min in one session, three times a week for 12 weeks. Knee-to-knee length (KTKL), hip-knee-ankle angle (HKAA), hip inclination angle (HIA), and medial proximal tibial angle (MPTA) were assessed to evaluate lower-extremity alignment. To evaluate knee pain, the short form-McGill Pain Questionnaire (SF-MPQ) were used. There was a significant difference between the groups, and a decrease of 16% in KTKL (from 6.48 ± 1.26 cm to 5.47 ± 1.21 cm) was shown in EG. Other variables, including HKAA, HIA, and MPTA on the right side, showed significant differences between pre- and post-intervention in EG (p < 0.01, p < 0.01, and p < 0.01, respectively). SF-MPQ score improved with 45% from 18.75 ± 1.64 to 10.33 ± 2.47 after exercise intervention in EG. These results suggest that the combined exercise program, including strength and neuromuscular exercises, is an effective intervention for improving lower-extremity alignment and knee pain in middle-aged women with genu varum.

Thoracic hyperkyphosis is associated with postural abnormality, physical function, and quality of life. This study aimed to examine the effects of a combined exercise program on the spinal curvature and balance ability in adolescents with kyphosis. Fifty-one adolescents (mean age 21.95 ± 3.90 year, 23 male and 28 female) diagnosed with kyphosis were randomly divided into two groups: an experimental group (n = 25) and a control group (n = 26). All participants in the study group underwent a combined exercise program for 60 min, three times per week, for 12 weeks. Cobb’s angle and forward head angle showed significant differences between the two groups (p < 0.001). The anterior and posterior weight distributions of static and dynamic plantar foot pressures showed a significant difference between the two groups (p < 0.001), and significant differences were observed only in the study group (p < 0.001). However, the left and right static plantar foot pressures did not differ significantly. In conclusion, these results demonstrate that a combined exercise program is an effective intervention for the improvement of alignment in the spinal curve and balance in adolescents with postural kyphosis.

Background: Hepatic steatosis (HS) can be comprehensively assessed by visually comparing the hepatic and vessel attenuation on unenhanced computed tomography (CT). We aimed to evaluate the reliability and reproducibility of a CT-based visual grading system (VGS) for comprehensive assessment of HS., Methods: In this retrospective study, a four-point VGS based on the visual comparison of liver and hepatic vessels was validated by six reviewers with diverse clinical experience using the unenhanced CT images of 717 potential liver donors. The diagnostic performance of VGS and quantitative indices (difference and ratio of the hepatic and splenic attenuation) to diagnose HS were evaluated using multi-reader multi-case receiver operating characteristics (ROC) analysis (reference: pathology). The interobserver agreement was assessed using Fleiss κ statistics., Results: Using the VGS, all six reviewers showed areas under the ROC curves (AUROCs) higher than 0.9 for diagnosing total steatosis (TS) ≥ 30%, macrovesicular steatosis (MaS) ≥ 30%, and MaS ≥ 10%. No difference was noted between the AUROCs of the VGS and quantitative indices (p ≥ 0.1). The reviewers showed substantial agreement (Fleiss κ, 0.61). Most discrepancies occurred between the two lowest grades of VGS (81.5%; 233/283), in which most subjects (97.0%; 226/233) had a MaS < 10%. The average-reader sensitivity and specificity of the VGS were 0.80 and 0.94 to detect TS ≥ 30% and 0.93 and 0.81 to detect MaS ≥ 10%., Conclusion: VGS was reliable and reproducible in assessing HS. It may be useful as a non-invasive and simple tool for comprehensive HS assessment., (© 2022. Asian Pacific Association for the Study of the Liver.)

The usage of aqueous lubricants in eco-friendly bio-medical friction systems has attracted significant attention. Several bottle-brush polymers with generally ionic functional groups have been developed based on the structure of biological lubricant lubricin. However, hydrophilic nonionic brush polymers have attracted less attention, especially in terms of wear properties. We developed bottle-brush polymers (BP) using hydrophilic 2-hydroxyethyl methacrylate (HEMA), a highly biocompatible yet nonionic molecule. The lubrication properties of polymer films were analyzed in an aqueous state using a ball-on-disk, which revealed that BPHEMA showed a lower aqueous friction coefficient than linear poly(HEMA), even lower than hyaluronic acid (HA) and polyvinyl alcohol (PVA), which are widely used as lubricating polymers. Significantly, we discovered that the combination of HA, PVA, and BPHEMA is demonstrated to be essential in influencing the surface wear properties; the ratio of 1 : 2 (HA : BPHEMA) had the maximum wear resistance, despite a slight increase in the aqueous friction coefficient., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To evaluate the value of the contrast enhancing pattern on pre-treatment MRI for predicting the response to anti-angiogenic treatment in patients with IDH-wild type recurrent glioblastoma., Methods: This retrospective study enrolled 65 patients with IDH wild-type recurrent glioblastoma who received standard therapy and then received either bevacizumab (46 patients) or temozolomide (19 patients) as a secondary treatment. The contrast enhancing pattern on pre-treatment MRI was visually analyzed and dichotomized into contrast enhancing lesion (CEL) dominant and non-enhancing lesion (NEL) dominant types. Quantitative volumetric analysis was used to support the dichotomization. The Kaplan-Meier method and Cox proportional hazards regression analysis were used to stratify progression free survival (PFS) according to the treatment in the entire patients, CEL dominant group, and NEL dominant group., Results: In all patients, the PFS of those treated with bevacizumab was not significantly different from those treated with temozolomide (log-rank test, P = 0.96). When the contrast enhancing pattern was considered, bevacizumab was associated with longer PFS in the CEL dominant group (P = 0.031), whereas temozolomide showed longer PFS in the NEL dominant group (P = 0.022). Quantitative analysis revealed mean values for the proportion of solid-enhancing tumor of 13.7% for the CEL dominant group and 4.3% for the NEL dominant group., Conclusion: Patients with the CEL dominant type showed a better treatment response to bevacizumab, whereas NEL dominant types showed a better response to temozolomide. The contrast enhancing pattern on pre-treatment MRI can be used to stratify patients with IDH wild-type recurrent glioblastoma according to the effect of anti-angiogenic treatment., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To evaluate the effectiveness of the transradial artery approach (TRA) for treating malfunctioning arteriovenous fistulas (AVFs) in patients on hemodialysis., Materials and Methods: A retrospective analysis was conducted in this single-center study of TRA endovascular procedures in 73 patients (43 male and 30 female; mean age of 67.4 years (range, 42-92 years) with malfunctioning AVFs, between January 2008 and April 2019. Patients' baseline and lesion characteristics, technical and clinical success, and complications were evaluated, and functional patency was analyzed using the Kaplan-Meier method., Results: Radial artery approaches were successful in all patients. Angioplasty performed using the TRA achieved technical and clinical success rates of 98.6%(72/73) and 91.7%(67/73), respectively. The median primary patency time was 18.8 ± 15.9 months. The primary functional patency rates at 3, 6, and 12 months were 82.1%, 68.6%, and 63.9%, respectively. There were no major complications or adverse events, such as hand ischemia, related to the radial artery approach., Conclusion: In selected cases, the TRA can be used complementary to the transvenous approach to treat malfunctioning AVFs., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2022 The Korean Society of Radiology.)

Background: External bile stents may be used to prevent biliary complications. However, the external biliary stent itself has a risk of complications. This study evaluated the frequency and treatment of complications associated with external bile stent., Methods: From May 2015 to September 2019, 18 deceased donor liver transplantations (DDLTs) and 25 living donor liver transplantations (LDLTs) were performed. We retrospectively reviewed these patients' demographic profiles, type of transplantation and presence of biliary complications, external bile stent-related complications, and treatment results., Results: Overall biliary complications occurred in 12 patients (27.9%): 3 strictures (6.9%), 2 leakages (4.6%), and 7 external bile stent-related complications (16.2%). Among the 7, 4 were self-removal or stent fractures at home, and 2 occurred after removal by a physician. One patient had ileus with peritonitis. Local peritonitis was controlled by antibiotics and fluid therapy, but 1 patient needed an operation because of intestinal obstruction with recurrent local peritonitis. All biliary complications occurred in LDLT, and external biliary stent-related complications also occurred only in LDLT, not in DDLT (P = .014). Interestingly, only 1 of 7 external bile stent-related complications occurred after we adopted the stent buried suture technique on the duodenum (P = .062)., Conclusions: External bile stent-related complications were higher in LDLT than in DDLT. When performing external bile stent implantation, the stent buried suture technique will help reduce stent-related complications, especially in LDLT., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: Laparoscopic liver donor surgery is a technically difficult and demanding procedure. Our aim was toevaluate its feasibility at an established transplant center. Although our hospital is a small-volume center with <20 liver transplants per year, laparoscopic donor surgery has been performed regularly. In this study, we have reported our experiences with laparoscopic donor right hepa-tectomy and its outcomes., Materials and Methods: Between May 2014 and March 2021, 26 deceased donor liver transplants and 37 living donor liver transplants, approved by the Korean Network for Organ Sharing, were performed at out center. From these, we reviewed the medical records, including clinical and demographic characteristics and operative outcomes, of 3 living donors who under-went pure laparoscopic donor right hepatectomy and their recipients., Results: Each of the 3 laparoscopic donor right hepatectomies took over 10 hours with the prolonged Pringle maneuver time and warm ischemic time. However, there were no significant events during surgery or critical postoperative complications. In the recipients, posttransplant complications included middle hepatic vein obstruction, postoperative bleeding, bile leak, septic shock, and primary nonfunction of the graft. We managed and resolved these complications using various approaches, including retransplant, and all 3 recipients recovered and survived., Conclusions: Laparoscopic donor right hepatectomy had a relatively long operative time at our small-volume center. We believe that successful laparoscopic donor hepatectomy is possible if the donor is selected appropriately according to the center's experiences and there are constant efforts to overcome the learning curve.

The microtubule (MT) cytoskeleton is crucial for cell motility and migration by regulating multiple cellular activities such as transport and endocytosis of key components of focal adhesions (FA). The kinesin-13 family is important in the regulation of MT dynamics and the best characterized member of this family is the mitotic centromere-associated kinesin (MCAK/KIF2C). Interestingly, its overexpression has been reported to be related to increased metastasis in various tumor entities. Moreover, MCAK is involved in the migration and invasion behavior of various cell types. However, the precise molecular mechanisms were not completely clarified. To address these issues, we generated CRISPR/dCas9 HeLa and retinal pigment epithelium (RPE) cell lines overexpressing or downregulating MCAK. Both up- or downregulation of MCAK led to reduced cell motility and poor migration in malignant as well as benign cells. Specifically, it's up- or downregulation impaired FA protein composition and phosphorylation status, interfered with a proper spindle and chromosome segregation, disturbed the assembly and disassembly rate of FA, delayed cell adhesion, and compromised the plus-tip dynamics of MTs. In conclusion, our data suggest MCAK act as an important regulator for cell motility and migration by affecting the actin-MT cytoskeleton dynamics and the FA turnover, providing molecular mechanisms by which deregulated MCAK could promote malignant progression and metastasis of tumor cells.

Bone metastasis is a complication of prostate cancer in up to 90% of men afflicted with advanced disease. Therapies that reduce androgen exposure remain at the forefront of treatment. However, most prostate cancers transition to a state whereby reducing testicular androgen action becomes ineffective. A common mechanism of this transition is intratumoral production of testosterone (T) using the adrenal androgen precursor dehydroepiandrosterone (DHEA) through enzymatic conversion by 3β- and 17β-hydroxysteroid dehydrogenases (3βHSD and 17βHSD). Given the ability of prostate cancer to form blastic metastases in bone, we hypothesized that osteoblasts might be a source of androgen synthesis. RNA expression analyses of murine osteoblasts and human bone confirmed that at least one 3βHSD and 17βHSD enzyme isoform was expressed, suggesting that osteoblasts are capable of generating androgens from adrenal DHEA. Murine osteoblasts were treated with 100 nM and 1 μM DHEA or vehicle control. Conditioned media from these osteoblasts were assayed for intermediate and active androgens by liquid chromatography-tandem mass spectrometry. As DHEA was consumed, the androgen intermediates androstenediol and androstenedione were generated and subsequently converted to T. Conditioned media of DHEA-treated osteoblasts increased androgen receptor (AR) signaling, prostate-specific antigen (PSA) production, and cell numbers of the androgen-sensitive prostate cancer cell lines C4-2B and LNCaP. DHEA did not induce AR signaling in osteoblasts despite AR expression in this cell type. We describe an unreported function of osteoblasts as a source of T that is especially relevant during androgen-responsive metastatic prostate cancer invasion into bone. © 2021 American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA., (© 2021 American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Background: Updated response assessment in neuro-oncology (RANO) does not consider peritumoral non-enhancing lesion (NEL) and baseline (residual) contrast enhancement (CE) volume. The objective of this study is to explore helpful imaging characteristics to refine RANO for assessing early treatment response (pseudoprogression and time-to-progression [TTP]) in patients with IDH wild-type glioblastoma., Methods: This retrospective study enrolled 86 patients with IDH wild-type glioblastoma who underwent consecutive MRI examinations before and after concurrent chemoradiotherapy (CCRT). NEL was classified as edema- or tumor-dominant type on pre-CCRT MRI. CE evolution was categorized into 4 patterns based on post-operative residual CE (measurable vs. non-measurable) and CE volume change (same criteria with RANO) during CCRT. Multivariable logistic regression, including clinical parameters, NEL type, and CE evolution pattern, was used to analyze pseudoprogression rate. TTP and OS according to NEL type and CE evolution pattern was analyzed by the Kaplan-Meier method., Results: Pseudoprogression rate was significantly lower (chi-square test, P = .047) and TTP was significantly shorter (hazard ratio [HR] = 2.03, P = .005) for tumor-dominant type than edema-dominant type of NEL. NEL type was the only predictive marker of pseudoprogression on multivariate analysis (odds ratio = 0.26, P = .046). Among CE evolution patterns, TTP and OS was shortest in patients with residual CE compared with those exhibiting new CE (HR = 4.33, P < 0.001 and HR = 3.71, P = .009, respectively). In edema-dominant NEL type, both TTP and OS was stratified by CE evolution pattern (log-rank, P = .001), whereas it was not in tumor-dominant NEL., Conclusions: NEL type improves prediction of pseudoprogression and, together with CE evolution pattern, further stratifies TTP and OS in patients with IDH wild-type glioblastoma and may become a helpful biomarker for refining RANO.

Backgrounds/aims: Post-hepatectomy liver failure (PHLF) is a major concern for patients with hepatocellular carcinoma (HCC) who have undergone liver resection. The albumin-bilirubin (ALBI) score is a novel model for assessing liver function. We aimed to investigate the effectiveness of the ALBI score as a predictor of PHLF in HCC patients who have undergone hepatectomy in South Korea., Methods: Between January 2014 and November 2018, HCC patients who underwent hepatectomy and indocyanine retention rate at 15 min (ICG-R15) test were enrolled in this study., Results: A total of 101 patients diagnosed with HCC underwent hepatectomy. Thirty-two patients (31.7%) experienced PHLF. The ALBI score (OR 2.83; 95% CI 1.22-6.55; p=0.015), ICG-R15 (OR 1.07; 95% CI 1.02-1.12; p=0.007) and ALBI grade (OR 2,86; 95% CI 1.08-7.58; p=0.035) were identified as independent predictors of PHLF by multivariable analysis. The area under the receiver operating characteristic curve of the ALBI score and ICG-R15 were 0.676 (95% CI 0.566-0.785) and 0.632 (95% CI 0.513-0.752), respectively. The optimal cutoff value of the ALBI score in predicting PHLF was -2.62, with a sensitivity of 75.0% and a specificity of 56.5%., Conclusions: The ALBI score is an effective predictor of PHLF in patients with HCC, and its predictive ability is comparable to that of ICG-R15.

Six patients (mean age, 57.7 y ± 19.7) with persistent urinary fistulae underwent 7 urinary tract embolizations with AMPLATZER Vascular Plugs (AVPs) and glue: 5 with concomitant cavity obliteration with glue and 2 without. A single procedure was successful in resolving urinary leakage in 5 patients (71%) at a mean follow-up of 27.3 wk ± 31.5 (median, 9.7 wk; range, 4.9-80 wk). Repeat cavity embolization was required in 2 instances to achieve clinical success. Mean survival was 42.3 wk (median, 16.4 wk; range, 11.7-104 wk). Combined AVP and glue embolization may prove to be a primary approach in the control of persistent fistulae., (Copyright © 2020 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Non-HLA antibodies, anti-angiotensin II type 1 receptor antibodies (anti-AT1R) and anti-endothelial cell antibodies (AECA), are known to play a role in allograft rejection. We evaluated the role of both antibodies in predicting post-transplant outcomes in low-risk living donor kidney transplantation (LDKT) recipients., Methods: In 94 consecutive LDKT recipients who were ABO compatible and negative for pre-transplant HLA donor-specific antibodies, we determined the levels of anti-AT1Rs using an enzyme-linked immunosorbent assay and the presence of AECAs using a flow cytometric endothelial cell crossmatch (ECXM) assay with pre-transplant sera. Hazard ratio (HR) was calculated to predict post-transplant outcomes., Results: Pre-transplant anti-AT1Rs (≥11.5 U/mL) and AECAs were observed in 36 (38.3%) and 22 recipients (23.4%), respectively; 11 recipients had both. Pre-transplant anti-AT1Rs were a significant risk factor for the development of acute rejection (AR) (HR 2.09; P=0.018), while a positive AECA status was associated with AR or microvascular inflammation only (HR 2.47; P=0.004) throughout the follow-up period. In particular, AECA (+) recipients with ≥11.5 U/mL anti-AT1Rs exhibited a significant effect on creatinine and estimated glomerular filtration rate (P<0.001; P=0.028), although the risk of AR was not significant., Conclusions: Pre-transplant anti-AT1Rs and AECAs have independent negative effects on post-transplant outcomes in low-risk LDKT recipients. Assessment of both antibodies would be helpful in stratifying the pre-transplant immunological risk, even in low-risk LDKT recipients.

Background: The clinical implication of lymph node (LN) dissection of intrahepatic cholangiocarcinoma (ICCA) is still controversial, and LN metastasis (LNM) based on tumor site has not been confirmed yet., Methods: Patients who underwent curative-intent surgery at 10 tertiary referral centers were identified and divided into peripheral (PP) and near second confluence level tumor (NC) groups on the basis of the distance from the second confluence and oncological outcomes were compared., Results: Of 179 patients, 121 patients with LND were divided into the NC (n = 89) and PP groups (n = 32) on the basis of 4.5 cm from the second confluence. NC group showed higher LNM rate than PP group (46.1 vs 21.9%, p = 0.016) and NC was a risk factor for LNM (odds ratio: 4.367; 95% confidence interval: 1.234-15.453, p = 0.022). The 5-year overall survival (OS) rate (38.0% vs. 27.8%, p = 0.777) and recurrence-free survival (RFS) rates (22.8% vs. 25.8%, p = 0.742) showed no differences between the PP and NC groups. In the NC group, N1 patients showed worse 5-year OS (12.7% vs 39.0%, p = 0.004) and RFS (8.8% vs 28.6%, p = 0.004) than the N0 patients. In the PP group, discordant results in 5-year OS (48.9% vs. 50.0%, p = 0.462) and RFS (41.3% vs. 0%, p = 0.056) were found between the N0 and N1 patients., Conclusion: The NC group was an independent risk factor for LNM and LNM worsened prognosis in NC group for ICCA. In the PP group, LND should not be omitted because of high LNM rate and insufficient oncologic evidence., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Most patients who undergo liver transplantation (LT) have advanced cirrhosis and poor nutritional status. The aim of this study was to investigate the effect of enteral nutrition (EN) on the clinical outcomes after LT., Methods: From 2015 to 2019, the medical records of recipient of LT at Kosin University Gospel Hospital were retrospectively reviewed., Results: Thirty-seven patients underwent LT. Nineteen patients underwent living donor liver transplantation (LDLT) and 18 patients underwent deceased donor liver transplantation (DDLT). One LDLT patient was excluded because transplantation was done within 1 month. Five DDLT patients were excluded either because they died within 1 month (n=4) or received transplantation within 1 month. (n=1). Therefore, 31 patients were analyzed. Psoas-muscle index (P=0.715) and serum albumin (P=0.111) were not statistically different between the LDLT and DDLT groups. Four patients (4/31) were readmitted because of infection. One LDLT patient was diagnosed with genitourinary infection. The three DDLT patients were diagnosed with pulmonary tuberculosis (n=1), diverticulitis (n=1), and sepsis (n=1). Readmission caused by infection was not statistically different between LDLD and DDLT patients (P=0.284). Preoperative EN <25% of the recommended amount (P=0.016) was significantly associated with readmission related to infection. In multivariate analyses, preoperative EN <25% was an independent risk factor for readmission due to infection after LT regardless of psoas-muscle index, baseline Model for End-Stage Liver Disease score, or LT type., Conclusions: Preoperative poor EN is significantly associated with readmission risk due to infection within 3 months of LT., (© The Korean Society for Transplantation.)

Background/aims: The Korean National Cancer Screening Program recommends biennial gastric cancer screening for patients aged ≥40 years. This study compared the characteristics of asymptomatic young gastric cancer patients aged <40 years, whose cancer was detected during a health checkup (screening group), with those whose disease was detected because of symptoms (diagnostic group)., Methods: Data were collected retrospectively from 84 subjects who underwent a gastroduodenoscopy before the age of 40 years and who were diagnosed with gastric cancer from January 2006 to February 2017 in three tertiary centers in Korea. The clinicopathological characteristics, including age, sex, stage, location, pathology, and survival, were compared according to the purpose of endoscopy (screening group, n=23 vs. diagnostic group, n=61)., Results: The median age of the screening group was higher than that of the diagnostic group (37 vs. 35 years, p=0.027), as was the proportion of early gastric cancer cases (78.3% vs. 29.5%, p<0.01), curative endoscopic treatment or operation rate (95.7% vs. 52.5%, p<0.01), and the overall survival (p<0.01). Poorly differentiated or signet ring cell carcinoma was less common in the screening group than in the diagnostic group (56.5% vs. 83.6%, p=0.006). The sex ratio, smoking status, family history of gastric cancer, Helicobacter pylori infection status, and tumor location were similar in the two groups., Conclusions: Screening gastroduodenoscopy may enable the early detection of gastric cancer and prolong survival in patients <40 years of age.

Purpose: Renal dysfunction is a common complication and one of the factors that affects the outcomes of liver transplantation (LT). The aim of this study was to review the clinical course of recipients of LT who needed peritransplant dialysis at our center., Methods: We compared the clinical demographics, morbidity, and mortality between patients who required and those who did not require peritransplant dialysis among 26 recipients of LT from May 2015 to February 2018 at our center., Results: Among the recipients, 9 had pretransplant or posttransplant dialysis and 17 did not. The patients who underwent dialysis had a higher pretransplant Model for End-Stage Liver Disease score (42 vs 13; P < .001), older donor age (41 vs 24 years; P < .001), and longer post-LT hospital stay (37 vs 20 days; P < .001). However, there was no significant difference in the serum creatinine level between the 2 groups (1.36 vs 0.93 mg/dL; P = .187) at 2 weeks (1.10 vs 0.96 mg/dL; P = .341), 1 month (1.06 vs 0.86 mg/dL; P = .105), and 3 months after LT (0.92 vs 0.94 vs 0.89 mg/dL; P = .825). Mortality was higher in the peritransplant dialysis group (P = .043). The pre-LT dialysis duration was significantly related to post-LT dialysis (P = .028) and mortality (P = .011)., Conclusions: The pre-LT dialysis duration is considered an important factor in the survival and recovery of kidney function after LT. Therefore, if the patient has started dialysis, it may be beneficial to proceed to LT as soon as possible., (Copyright © 2019. Published by Elsevier Inc.)

Bone metastasis is a painful complication of advanced prostate cancer. Endothelin-1 is a tumor-secreted factor that plays a central role in osteoblast activation and the osteosclerotic response of prostate cancer metastatic to bone. Antagonists that block the activation of the endothelin A receptor (ETAR), located on osteoblasts, reduce osteoblastic bone lesions in animal models of bone metastasis. However, ETAR antagonists demonstrated limited efficacy in clinical trials of men with advanced prostate cancer who also received standard androgen deprivation therapy (ADT). Previous data from our group suggested that, in a mouse model, ETAR antagonists might only be efficacious when androgen signaling in the osteoblast is lowered beyond the ability of standard ADT. This notion was tested in a mouse model of prostate cancer bone metastasis. Castrated and sham-operated male athymic nude mice underwent intracardiac inoculation of the ARCaPM castration-resistant prostate cancer cell line. The mice were then treated with either the ETAR antagonist zibotentan or a vehicle control to generate four experimental groups: vehicle+sham (Veh+Sham), vehicle+castrate (Veh+Castr), zibotentan+sham (Zibo+Sham), and zibotentan+castrate (Zibo+Castr). The mice were monitored radiographically for the development of skeletal lesions. The Zibo+Castr group had significantly longer survival and a single incidental lesion. Mice in the Zibo+Sham group had the shortest survival and the largest number of skeletal lesions. Survival and skeletal lesions of the Veh+Sham and Veh+Castr groups were intermediate compared with the zibotentan-treated groups. We report a complex interaction between ETAR and androgen signaling, whereby ETAR blockade was most efficacious when combined with complete androgen deprivation., (Published by Oxford University Press on behalf of the Endocrine Society 2019.)

The objectives of this study were to evaluate the effects of community-based walking training (CWT) on the walking ability and fall-related self-efficacy of chronic stroke patients and compare the effects of CWT to the conventional walking programs in stroke patients. Previous studies focused on walking speed, walking endurance, and balance. However, no studies have examined the changes in fall-related self-efficacy after CWT. In order to achieve purpose of this study, 45 chronic stroke patients, who were hospitalized at National Rehabilitation Center, were randomly divided into the CWT group (CWTG, n=15), the treadmill walking training group (TWTG, n=15), and the control group (CG, n=15). The treatment was conducted 3 times per week (30 min each) for 4 weeks. CWT was carried out by gradually increasing the difficulty level in various environments outside the hospital room. The results revealed that the CWTG was more effective in enhancing the walking ability and fall-related self-efficacy than the TWTG and the CG. These findings demonstrated that the CWTG increased the walking ability and fall-related self-efficacy of chronic stroke patients. Therefore, we suggest that adding CWT to standard rehabilitation might be an effective method for improving walking ability and fall-related self-efficacy in chronic stroke patients., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported.

Background : Progression of metastatic liver carcinoma from any original cancer is aggressive and the prognosis is very poor. Therefore the new model that is easily approachable to study the propagation and prognosis of metastatic liver carcinoma is necessary. The aim of this study is to confirm the tumor formation and metastatic activity of anaplastic thyroid cancer and to support the research basis for the next generation cancer treatment that is to be developed, by carrying out additional experiments like cytokine stimulation. We investigated sequential findings of immunohistochemistry of rabbit hepatic malignancy induced by AX7 cells. Methods : 13 rabbits implanted with AX7 cells directly into liver parenchyme with laparotomy were investigated by histopathology examination, immunohistochemistry, which is useful for the evaluation of metastatic cancer angiogenesis. Growing tissue at the edge of the mass was collected and placed in the petri dish filled with saline. After removing necrotic and fibrous tissue, tumor tissue was cut into pieces, placed in saline, and extracted during the experiment. Results : Tumor growth and malignancy was confirmed on the 10th day after AX7 cells were implanted into liver. Positive for VEGF staining was found in the cytoplasm or cell membrane. The scores for VEGF stained cells were moderately positive (++) on day 10, strongly positive (+++) on day 44. Ki-67-positive hepatocytes reached at 65% on day 10, at 65.78% on day 14, at 66.4% on day 30, at 67.88% on day 44. Conclusion : AX7 cells implanted into liver can be used as a new rabbit metastatic liver carcinoma model and would become useful for human metastatic liver carcinoma studies. Future studies may facilitate the establishment of an effective systemic therapy for the metastatic liver cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Thirty per cent of cancer patients develop spine metastases with a substantial number leading to spinal cord compression and neurological deficits. Many demonstrate a propensity toward metastasis to the posterior third of the vertebral body. The dura, the outer layer of the meninges, lies in intimate contact with the posterior border of the vertebral body and has been shown to influence adjacent bone. The effects of the dura on bone marrow and cancer cells have not been examined. Understanding the biology of spinal metastasis will provide insights into mechanisms of cancer growth and allow for new treatment strategies., Objective: To examine the extent to which dura influences bone marrow/tumor cell metastatic characteristics., Methods: Dura conditioned media (DCM) from primary dura was examined for the ability to stimulate tumor cell proliferation/invasion and to alter bone marrow cell populations. RNA sequencing of dural fibroblasts was performed to examine expression of cytokines and growth factors., Results: DCM induced a significant increase in invasion and proliferation of multiple tumor cell lines, and of patient-derived primary spinal metastatic cells. DCM also increased the proliferation of bone marrow myeloid cells, inducing expression of immunosuppressive markers. RNA sequencing of dural fibroblasts demonstrated abundant expression of cytokines and growth factors involved in cancer/immune pathways., Conclusion: Factors released by primary dural cells induce proliferation of tumor cells and alter bone marrow to create a fertile environment for tumor growth. The dura therefore may play an important role in the increased incidence of metastases to adjacent bone.

Background: East Asia is a known endemic area for hepatitis B, and living donor liver transplantation is mainly performed. Liver retransplantation (ReLT) is expected to become an increasing problem because of a shortage of organs. This study aimed to compare early and late ReLT with consideration of specific circumstances and disease background of East Asians., Methods: Between October 1996 and January 2015, 51 patients underwent ReLT; we performed a retrospective analysis of data obtained from medical records of the patients. Clinical characteristics, indication, causes of death, survival rate, and prognostic factors were investigated., Result: The survival rate for early ReLT (n = 18) was 51.5% and that for late ReLT (n = 33) was 50.1% at 1 year postoperatively. Continuous venovenous hemodialysis and the use of mechanical ventilators were more frequent, and pre-retransplant intensive care unit stay and prothrombin time was longer in early ReLT than in late ReLT. Operation time was longer and the amount of intraoperative blood loss was greater in late ReLT than in early ReLT. Multivariate analysis showed that a higher C-reactive protein level increased mortality in early ReLT (P = .045), whereas a higher total bilirubin level increased the risk of death in late ReLT (P = .03)., Conclusion: Patients with early ReLT are likely to be sicker pre-retransplantation and require adequate treatment of the pretransplant infectious disease. On the other hand, late ReLT is likely to be technically more difficult and should be decided before the total bilirubin level increases substantially., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We induced a terpyridine moiety into a norbornene-based polymer to demonstrate its self-healing property, without an external stimulus, such as light, heat, or healing agent, using metal⁻ligand interactions. We synthesized terpyridine incorporated norbornene-based polymers using a ring-opening metathesis polymerization. The sol state of diluted polymer solutions was converted into supramolecular assembled gels, through the addition of transition metal ions (Ni 2+ , Co 2+ , Fe 2+ , and Zn 2+ ). In particular, a supramolecular complex gel with Zn 2+ , which is a metal with a lower binding affinity, demonstrated fast self-healing properties, without any additional external stimuli, and its mechanical properties were completely recovered.

Background: Tumor location is a prognostic factor for survival in patients with T2 gallbladder cancer. However, the optimal extent of resection according to tumor location remains unclear., Methods: We reviewed the records of 192 patients with T2 gallbladder cancer who underwent R0 or R1 resection at 6 institutions. Perioperative and oncologic outcomes were compared according to the extent of resection between hepatic-sided (n = 93) and peritoneal-sided (n = 99) tumors., Results: After a median follow-up of 30 months, the 5-year overall survival (84.9% vs 71.8%, P = .048) and recurrence-free survival (74.6% vs 62.2%, P = .060) were greater in peritoneal-sided T2 patients than in hepatic-sided T2 patients. Among hepatic-sided T2 patients, the 5-year overall survival was greater in patients who underwent radical cholecystectomy including lymph node dissection with liver resection than in patients who underwent lymph node dissection without liver resection (80.3% vs 30.0%, P = .032), and the extent of liver resection was not associated with overall survival (P = .526). Lymph node dissection without liver resection was an independent prognostic factor for overall survival in hepatic-sided T2 gallbladder cancer (hazard ratio 5.009, 95% confidence interval 1.512-16.596, P = .008). In peritoneal-sided T2 patients, the 5-year overall survival was not significantly different between the lymph node dissection with liver resection and the lymph node dissection without liver resection subgroups (70.5% vs 54.8%, P = .111) and the extent of lymph node dissection was not associated with overall survival (P = .395)., Conclusion: In peritoneal-sided T2 gallbladder cancer, radical cholecystectomy including lymph node dissection without liver resection is a reasonable operative option. Radical cholecystectomy including lymph node dissection with liver resection is suitable for hepatic-sided T2 gallbladder cancer., (Copyright © 2017 Elsevier Inc. All rights reserved.)