Background/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC. Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy. Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC. Conclusions Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.

Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.

Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.

Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.

Background: The retinoblastoma (RB) protein which is encoded by RB gene selectively provides a cell type-specific function in malignancies. In colorectal carcinoma, RB has been highly expressed and related cyclin/cyclin-dependent kinase 4/6 inhibitors have shown improved therapeutic effects in some patients. However, little is known about RB in small intestinal adenocarcinoma (SIAC). Methods: Here, we conducted a multi-institutional study of RB expression in 229 surgically resected SIACs to explore the clinicopathologic and prognostic implications and the relationship with microsatellite instability (MSI) status and KRAS mutations. Results: High RB expression (RBHigh ) was more commonly observed in SIACs (76/229, 33%) than in normal small intestinal mucosa (27/188, 14%; P < 0.001). RBHigh was associated with nodular growth patterns (P = 0.028), the absence of lymphovascular (P = 0.001) and perineural invasion (P = 0.048), and a lower T category (P = 0.042) and indicated better overall survival (P = 0.003). In multivariate analysis, RBHigh (P = 0.049) was an independent prognostic predictor of better prognosis, along with younger patient age (P = 0.049), the absence of retroperitoneal seeding (P = 0.004), lower tumor stage (P < 0.001), and MSI (P = 0.005). The prognostic impact of RB expression was consistently observed regardless of MSI status and specifically persistent in SIACs with lower stages (stages I and II). Conclusion RBHigh was related to favorable clinicopathologic SIAC characteristics and indicated better patient prognosis. The prognostic predictability of RB was found in SIACs with lower stages, independent of MSI status. RB expression is a reliable and potent prognostic indicator for SIAC and may aid in selecting chemotherapy for patients.

In Walker’s nonmetric method, the nuchal crest serves as the representative region for indicating sexual dimorphism in cranial bones. However, the accuracy of sex estimation using the nuchal crest is lower than that using other anatomical regions. Furthermore, because of the protruding processes and structurally challenging features characterized by uneven and rough surfaces, there is a lack of metric methods for sex estimation, making quantification challenging. In this study, we aimed to validate a derived metric method for sex estimation by reconstructing the nuchal crest region in threedimensional (3D) images obtained from computed tomography scans of cranial bones and compare its accuracy with that of the nonmetric method. A total of 648 images were collected, with 100 randomly selected for use in the nonmetric method.We applied our metric method to the remaining 548 images. Our findings showed that the surface area of the nuchal crests was greater in male individuals than in female individuals. The nuchal crest surface area quantified by the metric method increased the accuracy of sex estimation by 48% compared with that by the nonmetric method. Our metric method for sex estimation, which quantifies the nuchal crest surface area using 3D images of the skull, led to a high sex estimation accuracy of 93%. Future studies should focus on proposing and quantifying new measurement methods for areas showing sexual characteristics in the skull that are difficult to measure, thereby enhancing the accuracy and reliability of sex estimation in human skeletal identification across various fields.

In Walker’s nonmetric method, the nuchal crest serves as the representative region for indicating sexual dimorphism in cranial bones. However, the accuracy of sex estimation using the nuchal crest is lower than that using other anatomical regions. Furthermore, because of the protruding processes and structurally challenging features characterized by uneven and rough surfaces, there is a lack of metric methods for sex estimation, making quantification challenging. In this study, we aimed to validate a derived metric method for sex estimation by reconstructing the nuchal crest region in threedimensional (3D) images obtained from computed tomography scans of cranial bones and compare its accuracy with that of the nonmetric method. A total of 648 images were collected, with 100 randomly selected for use in the nonmetric method.We applied our metric method to the remaining 548 images. Our findings showed that the surface area of the nuchal crests was greater in male individuals than in female individuals. The nuchal crest surface area quantified by the metric method increased the accuracy of sex estimation by 48% compared with that by the nonmetric method. Our metric method for sex estimation, which quantifies the nuchal crest surface area using 3D images of the skull, led to a high sex estimation accuracy of 93%. Future studies should focus on proposing and quantifying new measurement methods for areas showing sexual characteristics in the skull that are difficult to measure, thereby enhancing the accuracy and reliability of sex estimation in human skeletal identification across various fields.

In Walker’s nonmetric method, the nuchal crest serves as the representative region for indicating sexual dimorphism in cranial bones. However, the accuracy of sex estimation using the nuchal crest is lower than that using other anatomical regions. Furthermore, because of the protruding processes and structurally challenging features characterized by uneven and rough surfaces, there is a lack of metric methods for sex estimation, making quantification challenging. In this study, we aimed to validate a derived metric method for sex estimation by reconstructing the nuchal crest region in threedimensional (3D) images obtained from computed tomography scans of cranial bones and compare its accuracy with that of the nonmetric method. A total of 648 images were collected, with 100 randomly selected for use in the nonmetric method.We applied our metric method to the remaining 548 images. Our findings showed that the surface area of the nuchal crests was greater in male individuals than in female individuals. The nuchal crest surface area quantified by the metric method increased the accuracy of sex estimation by 48% compared with that by the nonmetric method. Our metric method for sex estimation, which quantifies the nuchal crest surface area using 3D images of the skull, led to a high sex estimation accuracy of 93%. Future studies should focus on proposing and quantifying new measurement methods for areas showing sexual characteristics in the skull that are difficult to measure, thereby enhancing the accuracy and reliability of sex estimation in human skeletal identification across various fields.

In Walker’s nonmetric method, the nuchal crest serves as the representative region for indicating sexual dimorphism in cranial bones. However, the accuracy of sex estimation using the nuchal crest is lower than that using other anatomical regions. Furthermore, because of the protruding processes and structurally challenging features characterized by uneven and rough surfaces, there is a lack of metric methods for sex estimation, making quantification challenging. In this study, we aimed to validate a derived metric method for sex estimation by reconstructing the nuchal crest region in threedimensional (3D) images obtained from computed tomography scans of cranial bones and compare its accuracy with that of the nonmetric method. A total of 648 images were collected, with 100 randomly selected for use in the nonmetric method.We applied our metric method to the remaining 548 images. Our findings showed that the surface area of the nuchal crests was greater in male individuals than in female individuals. The nuchal crest surface area quantified by the metric method increased the accuracy of sex estimation by 48% compared with that by the nonmetric method. Our metric method for sex estimation, which quantifies the nuchal crest surface area using 3D images of the skull, led to a high sex estimation accuracy of 93%. Future studies should focus on proposing and quantifying new measurement methods for areas showing sexual characteristics in the skull that are difficult to measure, thereby enhancing the accuracy and reliability of sex estimation in human skeletal identification across various fields.