Purpose: This study evaluated the clinical outcomes and prognostic factors in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX followed by local-regional therapy (LRT), surgical resection (SR), and radiotherapy (RT). We aimed to identify specific patient subgroups for which RT may serve as a reasonable alternative to SR for local tumor control. Methods: We retrospectively analyzed 116 patients (SR group, n= 70; RT group, n= 46) at a single center between 2015 and 2020. Survival outcomes were compared based on LRT modalities, focusing on identifying subgroups in which RT provided an efficacy comparable to that of SR. Results: Among 116 patients, the SR group achieved a significantly higher 5-year overall survival (OS) than the RT group (27.1% vs. 8.7%, P< 0.0001), despite similar progression-free survival (P= 0.23). Significant prognostic factors for OS included carbohydrate antigen 19-9 (CA19-9) response in BRPC (P= 0.02) and radiologic partial response in LAPC (P= 0.05). Subgroup analysis revealed that, while SR provided a survival advantage in CA19-9 responders, no significant difference in OS was observed between SR and RT in CA19-9 non-responders (P= 0.37). Conclusion Although surgery remains the gold standard, RT may be considered a justifiable local alternative for CA19-9 non-responders and surgically ineligible patients with LAPC, yielding comparable outcomes in these specific, biologically unfavorable subgroups.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

A 7-year-old, 2.6 kg, spayed female Maltese dog was referred for suspected congenital heart disease. The clinical signs included tachypnea, mild exercise intolerance, and cyanosis. Following echocardiography, the dog was diagnosed with a transitional atrioventricular septal defect (AVSD). The dog was also diagnosed with pulmonary hypertension due to congenital heart disease, which was likely secondary to volume overload caused by a large atrial septal defect.Management solely with sildenafil alone has produced favorable outcomes. This case report discusses transitional AVSD from the perspectives of terminology and embryology.

Chronic degenerative atrioventricular valve disease, particularly myxomatous mitral valve disease (MMVD), is the leading cause of heart failure in dogs.It significantly affects platelet function, especially under high shear stress, as well as potentially alters platelet activation and reactivity. Platelets are vital for coagulation and inflammation, and their function can be assessed using the Platelet Function Analyzer-200 (PFA-200), which simulates in vivo conditions. This study aimed to investigate the differences in closure time—measured using the PFA-200—in dogs with MMVD, with a focus on the impact of cardiac remodeling. The dogs were classified into the control, stage B1, stage B2, and stage C groups according to the American College of Veterinary Internal Medicine (ACVIM) guidelines. They were further categorized into the non-cardiac remodeling (normal, MMVD stage B1) and cardiac remodeling groups (MMVD stages B2 and C) based on cardiac remodeling status. Significant differences were found in the closure times of collagen-adenosine diphosphate (C/ADP) and collagen-epinephrine (C/EPI) between the non-cardiac and cardiac remodeling groups. Additionally, both closure times demonstrated a moderate positive correlation with the left atrial to aortic root ratio. Thus, assessing the closure times of C/ADP and C/EPI may provide valuable information for monitoring and staging MMVD in dogs.

Purpose: Even though pazopanib, a multitargeted tyrosine kinase inhibitor, has been approved for refractory soft tissue sarcoma (STS), little is known about the molecular determinants of the response to pazopanib. We performed integrative molecular characterization to identify potential predictors of pazopanib efficacy. Materials and Methods: We obtained fresh pre-treatment tumor tissue from 35 patients with advanced STS receiving pazopanib-based treatment. Among those, 18 (51.4%) received pazopanib monotherapy, and the remaining 17 (48.6%) received pazopanib in combination with durvalumab, programmed death-ligand 1 blockade. Whole-exome and transcriptome sequencing were performed for each tumor and patient germline DNA. Results: Of the 35 patients receiving pazopanib-based treatment, nine achieved a partial response (PR), resulting in an objective response rate (ORR) of 27.3%, and the median progression-free survival (PFS) was 6.0 months. Patients with CDK4 amplification (copy ratio tumor to normal > 2) exhibited shorter PFS (3.7 vs. 7.9 months, p=2.09×10–4) and a poorer response (ORR; 0% vs. 33.3%) compared to those without a gene amplification (copy ratio ≤ 2). Moreover, non-responders demonstrated transcriptional activation of CDK4 via DNA amplification, resulting in cell cycle activation. In the durvalumab combination cohort, seven of the 17 patients (41.2%) achieved a PR, and gene expression analysis revealed that durvalumab responders exhibited high immune/stromal cell infiltration, mainly comprising natural killer cells, compared to non-responders as well as increased expression of CD19, a B-cell marker. Conclusion Despite the limitation of heterogeneity in the study population and treatment, we identified possible molecular predictors of pazopanib efficacy that can be employed in future clinical trials aimed at evaluating therapeutic strategies.

Objective: To examine the usefulness and feasibility of modified thread carpal tunnel release (TCTR) by comparing the results of using pre-existing commercial thread with those of a newly developed thread (Smartwire-01). Methods: A total of 17 cadaveric wrists were used in the study. The modified TCTR method was practiced by two different experts. Pre-existing commercial surgical dissecting thread (Loop&ShearTM) was used for five wrists and the newly developed Smartwire-01 was used for twelve wrists. The gross and microanatomy of the specimens were evaluated by a blinded anatomist. Results: Both types of thread were able to cut the TCL similarly. Gross anatomy and histologic findings showed that there was no significant difference between the two types of threads. However, the practitioners felt that it was easier to cut the TCL using the newly-developed thread. Conclusion TCTR using Smartwire-01 was as effective as pre-existing Loop&ShearTM, with better user experiences.

OBJECTIVES: We examined whether pericardial adipose tissue (PAT) is predictive of prediabetes and type 2 diabetes over time. METHODS: In total, 2,570 adults without prediabetes/diabetes from the Coronary Artery Risk Development in Young Adults Study were followed up over 15 years. PAT volume was measured by computed tomography scans, and the new onset of prediabetes/diabetes was examined 5 years, 10 years, and 15 years after the PAT measurements. Multivariable Cox regression models were used to examine the association between the tertile of PAT and incident prediabetes/diabetes up to 15 years later. The predictive ability of PAT (vs. waist circumference [WC], body mass index [BMI], waist-to-height ratio [WHtR]) for prediabetes/diabetes was examined by comparing the area under the receiver operating characteristic curve (AUC). RESULTS: The highest tertile of PAT was associated with a 1.56 times (95% confidence interval [CI], 1.03 to 2.34) higher rate of diabetes than the lowest tertile; however, no association was found between the highest tertile of PAT and prediabetes in the fully adjusted models, including additional adjustment for BMI or WC. In the fully adjusted models, the AUCs of WC, BMI, WHtR, and PAT for predicting diabetes were not significantly different, whereas the AUC of WC for predicting prediabetes was higher than that of PAT. CONCLUSIONS PAT may be a significant predictor of hyperglycemia, but this association might depend on the effect of BMI or WC. Additional work is warranted to examine whether novel adiposity indicators can suggest advanced and optimal information to supplement the established diagnosis for prediabetes/diabetes.

Objective: : The percutaneous thread transection technique is a surgical dissecting method using a dissecting thread inserted through a needle under ultrasound guidance without skin incision. As the new dissecting threads were developed domestically, this cadaver study was conducted to compare the effectiveness and safety between the new threads (ultra V sswire and smartwire-01) and a pre-existing commercial dissecting thread (loop & shear) by demonstrating a modified looped thread cubital tunnel release. Methods: : The percutaneous cubital tunnel release procedure was performed on 29 fresh cadaveric upper extremities. The preexisting commercial thread was used in 5 upper extremities. The two newly developed threads were used in 24 upper extremities. Two practitioners performed the procedures separately. After the modified looped thread cubital release, anatomical and histological analyses were performed by a blinded anatomist. The presence of the dissected cubital tunnel and damaged adjacent soft tissue was assessed. Results: : Out of the 29 cadaveric upper extremities, 27 specimens showed complete dissection of the Osborne ligament and the proximal fascia of the flexor carpi ulnaris muscle. One specimen was incompletely dissected in each of the ultra V sswire and smartwire-01 groups. There were no injuries of adjacent structures including the ulnar nerve, ulnar artery, medial antebrachial cutaneous nerve, or flexor tendon with either the commercial thread or the newly developed threads. The anatomical analysis revealed clear and sharp incisional margins of the cubital tunnel in the Smartwire-01 and loop & shear groups. All three kinds of threads maintained proper linear elasticity for easy handling during the procedure. The smartwire-01 provided higher visibility in ultrasound than the other threads. Conclusion : The newly developed threads were effective and safe for use in the thread cubital tunnel release procedure.