In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Purpose: There are clinical unmet needs in predicting therapeutic response and precise strategy for the patient with advanced biliary tract cancer (BTC). We aimed to identify genomic alterations predicting therapeutic response and resistance to gemcitabine and cisplatin (Gem/Cis)-based chemotherapy in advanced BTC. Materials and Methods: Genomic analysis of advanced BTC multi-institutional cohorts was performed using targeted panel sequencing. Genomic alterations were analyzed integrating patients’ clinicopathologic data, including clinical outcomes of Gem/Cis-based therapy. Significance of genetic alterations was validated using clinical next-generation sequencing (NGS) cohorts from public repositories and drug sensitivity data from cancer cell lines. Results: 193 BTC patients from three cancer centers were analyzed. Most frequent genomic alterations were TP53 (55.5%), KRAS (22.8%), ARID1A (10.4%) alterations, and ERBB2 amplification (9.8%). Among 177 patients with BTC receiving Gem/Cis-based chemotherapy, ARID1A alteration was the only independent predictive molecular marker of primary resistance showing disease progression for 1st-line chemotherapy in the multivariate regression model (odds ratio, 3.12; p=0.046). In addition, ARID1A alteration was significantly correlated with inferior progression-free survival on Gem/Cis-based chemotherapy in the overall patient population (p=0.033) and in patients with extrahepatic cholangiocarcinoma (CCA) (p=0.041). External validation using public repository NGS revealed that ARID1A mutation was a significant predictor for poor survival in BTC patients. Investigation of multi-OMICs drug sensitivity data from cancer cell lines revealed that cisplatin-resistance was exclusively observed in ARID1A mutant bile duct cancer cells. Conclusion Integrative analysis with genomic alterations and clinical outcomes of the first-line Gem/Cis-based chemotherapy in advanced BTC revealed that patients with ARID1Aalterations showed a significant worse clinical outcome, especially in extrahepatic CCA. Well-designed prospective studies are mandatory to validate the predictive role of ARID1Amutation.

Background: Patient-centered management is becoming increasingly important in gout, but there are limited studies exploring patients' perspectives and preferences. We aimed to investigate patients' perspectives and preferences regarding gout and gout management, and their impacts on adherence to urate lowering therapy (ULT). Methods: A paper-based survey was performed in patients with gout seen at the rheumatology outpatient clinics of 16 tertiary hospitals. The survey included questions regarding demographics, comorbidities, gout attacks, current treatment and adherence, and patients' perspectives and preferences regarding gout and gout management. Multivariate regression analysis was performed to determine the factors associated with ULT adherence. Results: Of 809 surveyed patients with gout, 755 (94.5%) were using ULT. Among those using ULT, 89.1% had ≥ 80% adherence to ULT. Majority of the patients knew management strategies to some extent (94.8%), perceived gout as a life-long disease (91.2%), and were making efforts toward practicing at least one lifestyle modification (89.2%). Most patients (71.9%) obtained information about gout management during their clinic visits.Approximately half of the patients (53.6%) preferred managing their disease with both ULT and lifestyle modification, 28.4% preferred ULT only, and 17.4% preferred lifestyle modification only. Adherence was better in patients with older age (odds ratio [OR], 1.03), those with better knowledge of gout management strategies (OR, 3.56), and those who had preference for ULT (OR, 2.07). Conclusion Patients' perspectives and management preferences had high impacts on adherence to ULT in gout. Consideration of patients' perspectives and preferences is important for achieving the desired clinical outcome in gout.

Purpose: This study aimed to develop and validate a predictive model for the assessment of clinically significant prostate cancer (csPCa) in men, prior to prostate biopsies, based on bi-parametric magnetic resonance imaging (bpMRI) and clinical parameters. Materials and Methods: We retrospectively analyzed 300 men with clinical suspicion of prostate cancer (prostate-specific antigen [PSA] ≥ 4.0 ng/mL and/or abnormal findings in a digital rectal examination), who underwent bpMRI-ultrasound fusion transperineal targeted and systematic biopsies in the same session, at a Korean university hospital. Predictive models, based on Prostate Imaging Reporting and Data Systems scores of bpMRI and clinical parameters, were developed to detect csPCa (intermediate/high grade [Gleason score ≥ 3+4]) and compared by analyzing the areas under the curves and decision curves. Results: A predictive model defined by the combination of bpMRI and clinical parameters (age, PSA density) showed high discriminatory power (area under the curve, 0.861) and resulted in a significant net benefit on decision curve analysis. Applying a probability threshold of 7.5%, 21.6% of men could avoid unnecessary prostate biopsy, while only 1.0% of significant prostate cancers were missed. Conclusion This predictive model provided a reliable and measurable means of risk stratification of csPCa, with high discriminatory power and great net benefit. It could be a useful tool for clinical decision-making prior to prostate biopsies.

Background: Patient-centered management is becoming increasingly important in gout, but there are limited studies exploring patients' perspectives and preferences. We aimed to investigate patients' perspectives and preferences regarding gout and gout management, and their impacts on adherence to urate lowering therapy (ULT). Methods: A paper-based survey was performed in patients with gout seen at the rheumatology outpatient clinics of 16 tertiary hospitals. The survey included questions regarding demographics, comorbidities, gout attacks, current treatment and adherence, and patients' perspectives and preferences regarding gout and gout management. Multivariate regression analysis was performed to determine the factors associated with ULT adherence. Results: Of 809 surveyed patients with gout, 755 (94.5%) were using ULT. Among those using ULT, 89.1% had ≥ 80% adherence to ULT. Majority of the patients knew management strategies to some extent (94.8%), perceived gout as a life-long disease (91.2%), and were making efforts toward practicing at least one lifestyle modification (89.2%). Most patients (71.9%) obtained information about gout management during their clinic visits.Approximately half of the patients (53.6%) preferred managing their disease with both ULT and lifestyle modification, 28.4% preferred ULT only, and 17.4% preferred lifestyle modification only. Adherence was better in patients with older age (odds ratio [OR], 1.03), those with better knowledge of gout management strategies (OR, 3.56), and those who had preference for ULT (OR, 2.07). Conclusion Patients' perspectives and management preferences had high impacts on adherence to ULT in gout. Consideration of patients' perspectives and preferences is important for achieving the desired clinical outcome in gout.

Purpose: The purpose of this study was to investigate the diagnostic value of magnetic resonance imaging (MRI)–ultrasound (US) fusion transperineal targeted biopsy (FTB) and fusion template systematic biopsy (FSB) for prostate cancer (PCa) and clinically significant prostate cancer (csPCa) (intermediate/high grade [Gleason score ≥ 3+4]) based on bi-parametric MRI (bpMRI). Materials and methods: Retrospectively, we analyzed 300 patients with elevated prostate-specific antigen (≥ 4.0 ng/mL) and/or abnormal findings in a digital rectal examination at the Korea University Hospital. All 300 men underwent bpMRI-US fusion transperineal FTB and FSB in the period from April 2017 to March 2019. Results: PCas were detected in 158 of 300 men (52.7%), and the prevalence of csPCa was 34.0%. CsPCas were detected in 12 of 102 (11.8%) with Prostate Imaging-Reporting and Data System (PI-RADS) 3, 42 of 92 (45.7%) with PI-RADS 4, respectively; and 45 of 62 (72.6%) men with PI-RADS 5, respectively. BpMRI showed a sensitivity of 95.1% and negative predictive value of 89.6% for csPCa. FTB detected additional csPCa in 33 men (12.9%) compared to FSB. Compared to FTB, FSB detected additional csPCa in 10 men (3.9%). Conclusion BpMRI-US FTB and FSB improved detection of PCa and csPCa. The accuracy of bi-parametric MRI is comparable with that of multi-parametric MRI. Further, it is rapid, simpler, cheaper, and no side effects of contrast media. Therefore, it is expected that bpMRI-US transperineal FTB and FSB could be a good alternative to conventional US-guided transrectal biopsy, which is the current gold standard.

Background/Aims: Plug-assisted retrograde transvenous obliteration (PARTO) is widely used to manage gastric varices with a portosystemic shunt. It is not clear whether portal pressure and the incidence of complications increase after PARTO. The aim of this study was to determine the changes in portal pressure and the associated changes in liver func-tion, ascites, hepatic encephalopathy, and especially esopha-geal varix (EV) after PARTO. Methods: From March 2012 to February 2018, 54 patients who underwent PARTO were analyzed retrospectively. The parameters collected included liver function and episodes of cirrhotic complications before and at 1 and 6 months after PARTO. Results: The analysis of 54 patients showed improvement in liver function during the 6-month follow-up period (Model for End-Stage Liver Disease score: change from 11.46±4.35 to 10.33±2.96, p=0.021).Among these 54 patients, 25 patients were evaluated for their hepatic venous pressure gradient (HVPG) before and after PARTO (change from 12.52±3.83 to 14.68±5.03 mm Hg; p<0.001). Twenty-five patients with portal pressure mea-sured before and after PARTO were evaluated for risk factors affecting liver function improvement and EV deterioration. No factor associated with portal pressure was affected by liver function improvement. Post-PARTO portal pressure was a risk factor affecting EV deterioration (HVPG-post: odds ratio, 1.341; 95% confidence interval, 1.017 to 1.767; p=0.037). Conclusions The artificial blockade of the portosystemic shunt evidently leads to an increase in HVPG. Liver function was improved over the 6-month follow-up period. Portal pres-sure after PARTO was a significant risk factor for EV deterioration. Portal pressure measurement is helpful for predicting the patient’s clinical outcome.

PURPOSE: Enzyme-linked immunosorbent assay (ELISA) has been used in the diverse field to evaluate influenza virus infection; for the surveillance, diagnosis, efficacy evaluation, and development of the vaccine. The aim of this study was to establish an ELISA for detecting HA strain-specific antibodies using recombinant pandemic A H1N1 (pH1N1) HA1 (rHA1) protein. MATERIALS AND METHODS: rHA1 was produced in baculovirus system. The clinical performance of the developed ELISA was validated using human serum samples, by comparison with standard methods for detecting a neutralizing antibody; hemagglutination inhibition (HI) assay and microneutralization test (MNT). The ability of the ELISA system to evaluate the efficacy test of an influenza vaccine was explored by measuring antibody levels in the serum of vaccinated mice. RESULTS: Our ELISA could detect anti-rHA1 antibody in influenza-infected patients and vaccinated subjects. Compared to HI assay and MNT as reference methods, our method showed good performance in detection of anti-rHA1 antibody. Detection of the anti-rHA1 antibody in vaccinated mice and its correlation with titers in HI assay was also proved in a mice model. CONCLUSION: An ELISA system using rHA1 of pH1N1 influenza virus was developed, and showed good clinical performance in diagnosis of influenza virus infection and evaluation of the vaccination efficacy in both human and animal models.
Animals ; Antibodies ; Antibodies, Neutralizing ; Baculoviridae ; Diagnosis ; Enzyme-Linked Immunosorbent Assay* ; Hemagglutination ; Humans ; Influenza A virus ; Influenza Vaccines ; Influenza, Human* ; Methods ; Mice ; Models, Animal ; Orthomyxoviridae* ; Pandemics* ; Vaccination

OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) for chronic empyema-associated malignancy (CEAM). MATERIALS AND METHODS: We retrospectively reviewed the ¹⁸F-FDG PET/CT images of 33 patients with chronic empyema, and analyzed the following findings: 1) shape of the empyema cavity, 2) presence of fistula, 3) maximum standardized uptake value (SUV) of the empyema cavity, 4) uptake pattern of the empyema cavity, 5) presence of a protruding soft tissue mass within the empyema cavity, and 6) involvement of adjacent structures. Final diagnosis was determined based on histopathology or clinical follow-up for at least 6 months. The abovementioned findings were compared between the ¹⁸F-FDG PET/CT images of CEAM and chronic empyema. A receiver operating characteristic (ROC) analysis was also performed. RESULTS: Six lesions were histopathologically proven as malignant; there were three cases of diffuse large B-cell lymphoma, two of squamous cell carcinoma, and one of poorly differentiated carcinoma. Maximum SUV within the empyema cavity (p < 0.001) presence of a protruding soft tissue mass (p = 0.002), and involvement of the adjacent structures (p < 0.001) were significantly different between the CEAM and chronic empyema images. The maximum SUV exhibited the highest diagnostic performance, with the highest specificity (96.3%, 26/27), positive predictive value (85.7%, 6/7), and accuracy (97.0%, 32/33) among all criteria. On ROC analysis, the area under the curve of maximum SUV was 0.994. CONCLUSION: ¹⁸F-FDG PET/CT can be useful for diagnosing CEAM in patients with chronic empyema. The maximum SUV within the empyema cavity is the most accurate ¹⁸F-FDG PET/CT diagnostic criterion for CEAM.
Carcinoma, Squamous Cell ; Diagnosis ; Electrons ; Empyema ; Fistula ; Follow-Up Studies ; Humans ; Lymphoma, B-Cell ; Positron-Emission Tomography and Computed Tomography ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity