Purpose: Vascular endothelial growth factor tyrosine kinase inhibitors (TKIs) have been the standard of care for advanced and metastatic clear cell renal cell carcinoma (ccRCC). However, the therapeutic effect of TKI monotherapy remains unsatisfactory given the high rates of acquired resistance to TKI therapy despite favorable initial tumor response. Materials and Methods: To define the TKI-resistance mechanism and identify new therapeutic target for TKI-resistant ccRCC, an integrative differential gene expression analysis was performed using acquired resistant cohort and a public dataset. Sunitinib-resistant RCC cell lines were established and used to test their malignant behaviors of TKI resistance through in vitro and in vivo studies. Immunohistochemistry was conducted to compare expression between the tumor and normal kidney and verify expression of pathway-related proteins. Results: Integrated differential gene expression analysis revealed increased interferon-induced transmembrane protein 3 (IFITM3) expression in post-TKI samples. IFITM3 expression was increased in ccRCC compared with the normal kidney. TKI-resistant RCC cells showed high expression of IFITM3 compared with TKI-sensitive cells and displayed aggressive biologic features such as higher proliferative ability, clonogenic survival, migration, and invasion while being treated with sunitinib. These aggressive features were suppressed by the inhibition of IFITM3 expression and promoted by IFITM3 overexpression, and these findings were confirmed in a xenograft model. IFITM3-mediated TKI resistance was associated with the activation of TRAF6 and MAPK/AP-1 pathways. Conclusions These results demonstrate IFITM3-mediated activation of the TRAF6/MAPK/AP-1 pathways as a mechanism of acquired TKI resistance, and suggest IFITM3 as a new target for TKI-resistant ccRCC.

Purpose: This study aimed to assess the real-world clinical outcomes of consolidative durvalumab in patients with unresectable locally advanced non–small cell lung cancer (LA-NSCLC) and to explore the role of radiotherapy in the era of immunotherapy. Materials and Methods: This retrospective study assessed 171 patients with unresectable LA-NSCLC who underwent concurrent chemoradiotherapy (CCRT) with or without consolidative durvalumab at Asan Medical Center between May 2018 and May 2021. Primary outcomes included freedom from locoregional failure (FFLRF), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS). Results: Durvalumab following CCRT demonstrated a prolonged median PFS of 20.9 months (p=0.048) and a 3-year FFLRF rate of 57.3% (p=0.008), compared to 13.7 months and 38.8%, respectively, with CCRT alone. Furthermore, the incidence of in-field recurrence was significantly greater in the CCRT-alone group compared to the durvalumab group (26.8% vs. 12.4%, p=0.027). While median OS was not reached with durvalumab, it was 35.4 months in patients receiving CCRT alone (p=0.010). Patients positive for programmed cell death ligand 1 (PD-L1) expression showed notably better outcomes, including FFLRF, DMFS, PFS, and OS. Adherence to PACIFIC trial eligibility criteria identified 100 patients (58.5%) as ineligible. The use of durvalumab demonstrated better survival regardless of eligibility criteria. Conclusion The use of durvalumab consolidation following CCRT significantly enhanced locoregional control and OS in patients with unresectable LA-NSCLC, especially in those with PD-L1–positive tumors, thereby validating the role of durvalumab in standard care.

Purpose: We aimed to assess the effectiveness of early single intravesical administration of epirubicin in preventing intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma. Materials and Methods: Patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy between November 2018 and May 2022 were retrospectively reviewed. Intravesical epirubicin was administered within 48 hours if no evidence of leakage was observed. Epirubicin (50 mg) in 50 mL normal saline solution was introduced into the bladder via a catheter and maintained for 60 minutes. The severity of adverse events was graded using the Clavien-Dindo classification. We compared intravesical recurrence rate between the two groups. Multivariate analyses were performed to identify the independent predictors of bladder recurrence following radical nephroureterectomy. Results: Epirubicin (n=55) and control (n=116) groups were included in the analysis. No grade 1 or higher bladder symptoms have been reported. A statistically significant difference in the intravesical recurrence rate was observed between the two groups (11.8% at 1 year in the epirubicin group vs. 28.4% at 1 year in the control group; log-rank p=0.039). In multivariate analysis, epirubicin instillation (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.20 to 0.93; p=0.033) and adjuvant chemotherapy (HR, 0.29; 95% CI, 0.13 to 0.65; p=0.003) were independently predictive of a reduced incidence of bladder recurrence. Conclusion This retrospective review revealed that a single immediate intravesical instillation of epirubicin is safe and can reduce the incidence of intravesical recurrence after radical nephroureterectomy. However, further prospective trials are required to confirm these findings.

Background: To analyze the outcomes of clipping and coiling for ruptured intracranial aneurysms (RIAs) based on data from the National Health Insurance Service in South Korea, with a focus on variations according to region and hospital size. Methods: This study analyzed the one-year mortality rates for patients with RIAs who underwent clipping or coiling in 2018. Coiling was further categorized into non-stent assisted coiling (NSAC) and stent assisted coiling (SAC). Hospitals were classified as tertiary referral general hospitals (TRGHs), general hospitals (GHs), or semi-general hospitals (sGHs) based on size. South Korea’s administrative districts were divided into 15 regions for analysis. Results: In 2018, there were 2,194 (33.1%) clipping procedures (TRGH, 985; GH, 827; sGH, 382) and 4,431 (66.9%) coiling procedures (TRGH, 1,642; GH, 2076; sGH, 713) performed for RIAs treatment. Among hospitals performing more than 20 treatments, the one-year mortality rates following clipping or coiling were 11.2% and 16.0%, respectively, with no significant difference observed. However, there was a significant difference in one-year mortality between NSAC and SAC (14.3% vs. 19.5%, P = 0.034), with clipping also showing significantly lower mortality compared to SAC (P = 0.019). No significant differences in other treatment modalities were observed according to hospital size, but clipping at TRGHs had significantly lower mortality than at GHs (P = 0.042). While no significant correlation was found between the number of treatments and outcomes at GHs, at TRGHs, a higher volume of clipping procedures was significantly associated with lower total mortality (P = 0.023) and mortality after clipping (P = 0.022). Conclusion Using Korea NHIS data, mortality rates for RIAs showed no significant variation by hospital size due to coiling’s prevalence. However, differences in clipping outcomes by hospital size and volume in TRGH highlight the need for national efforts to improve clipping skills and standardization. Additionally, the higher mortality rate with SAC emphasizes the importance of precise indications for its application.

Objective: : To analyze the outcomes of coil embolization (CE) for unruptured intracranial aneurysm (UIA) according to region and hospital size based on National Health Insurance Service data in South Korea. Methods: : The incidence of complications, including intracranial hemorrhage (ICRH) and cerebral infarction (CI), occurring within 3 months and the 1-year mortality rates in UIA patients who underwent CE in 2018 were analyzed. Hospitals were classified as tertiary referral general hospitals (TRGHs), general hospitals (GHs) or semigeneral hospitals (sGHs) according to their size, and the administrative districts of South Korea were divided into 15 regions. Results: : In 2018, 8425 (TRGHs, 4438; GHs, 3617; sGHs, 370) CEs were performed for UIAs. Complications occurred in 5.69% of patients seen at TRGHs, 13.48% at GHs, and 20.45% at sGHs. The complication rate in TRGHs was significantly lower than that in GHs (p=0.039) or sGHs (p=0.005), and that in GHs was significantly lower than that in sGHs (p=0.030). The mortality rates in TRGHs, GHs, and sGHs were 0.81%, 2.16%, and 3.92%, respectively, with no significant difference. Despite no significant difference in the mortality rates, the complication rate significantly increased as the number of CE procedures per hospital decreased (p=0.001; rho=-0.635). Among the hospitals where more than 30 CEs were performed for UIAs, the incidence of CIs (p=0.096, rho=-0.205) and the mortality rates (3 months, p=0.048, rho=-0.243; 1 year, p=0.009, rho=-0.315) significantly decreased as the number of CEs that were performed increased and no significant difference in the incidence of post-CE ICRH was observed. Conclusion : The complication rate in patients who underwent CE for UIA increased as the hospital size and physicians’ experience in conducting CEs decreased. We recommend nationwide quality control policies CEs for UIAs.

This study examined the impact of perceived volume on satiety using 400 g kimchi fried rice in a normal rice bowl (Normal-400), 300 g kimchi fried rice in an augmented rice bowl with an elevated bottom (Illusion-300 and 300 g kimchi fried rice in a normal rice bowl (Normal-300). Thirty-six healthy women took part in this study once a week for three weeks. The Normal-400 (1st week), Illusion-300 (2nd week), and Normal-300 (3rd week) bowls were used to served kimchi fried rice to the same participants over three consecutive weeks. After each lunch, the consumption volume of fried rice, perception volume, and satiety rate were measured. The consumption volume of the fried rice was 313.8 g with the Normal-400, 248.9 g with the Illusion-300 and 240.2 g with the Normal-300. The perceived volume on an estimated five-point scale was 4.0 with the Normal-400, 4.1 with the Illusion-300 and 2.4 with the Normal-300. We compared the post-meal satiety of perceptually equal but quantitatively different amounts of food served in two different bowls (Normal-400 vs Illusion-300) and found that the participants felt equally full with both bowls despite having consumed significantly more food from the Normal-400. We also compared the post-meal satiety of perceptually different but quantitatively equal amounts of food in two different bowls (Illusion-300 vs Normal-300) and discovered that the subjects felt significantly fuller with the Illusion-300 although similar amounts of food were consumed from the two bowls. These two comparisons showed that visual cues play a critical role in determining satiety and that perceived volume is perhaps more important than the actual volume of consumed food, while in determining the level of fullness.

Purpose: To evaluate the performance of combining prostate health index (PHI) and Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) for detection of clinically significant prostate cancer (csPCa). Materials and Methods: We retrospectively reviewed patients who underwent prostate biopsy for elevated prostate-specific antigen (PSA) ≥2.5 ng/mL and/or abnormal digital rectal examination. Serum markers for PSA, free PSA (fPSA), and [-2] proPSA (p2PSA) were measured, and PHI was calculated as ([p2PSA/fPSA]×[PSA]1/2). Multiparametric magnetic resonance imaging was performed using a 3.0T scanner and scored using PI-RADSv2. csPCa was defined as either grade group (GG) ≥2 disease or GG1 cancer detected in >2 cores or >50% of positive on biopsy. Univariable and multivariable logistic regression modelling, along with receiver-operating characteristic (ROC) curve analysis was used to predict the probability of csPCa. Results: Of the total 358 patients, 159 (44.4%) were diagnosed with csPCa. On univariable analysis, age, PSA density (PSAD), PHI and PI-RADSv2 were associated with csPCa. The area under the ROC curve (AUC) of baseline model incorporating age and PSAD was 0.663. The AUC of combining PHI and PI-RADSv2 to baseline model was higher than that of PHI alone to baseline model (0.884 vs. 0.807, p<0.0001) and PI-RADSv2 alone to baseline model (0.884 vs. 0.846, p=0.0002), respectively. If biopsy was restricted to patients with PI-RADS 5 as well as PI-RADS 3 or 4 and PHI ≥27, 36.0% of unnecessary biopsy could be avoided at the cost of missing 4.7% of csPCa. Conclusions The combination of PHI and PI-RADSv2 to baseline model incorporating age and PSAD had higher accuracy for detection of csPCa compared with PHI or PI-RADSv2 alone.

Purpose: The purpose of study was to compare oncologic outcomes (recurrence-free survival [RFS], cancer-specific survival [CSS], and overall survival [OS]) and early complication (within 30 days) after radical cystectomy (RC) between old patients (70–79 aged) and oldest-old patients (above 80). Materials and Methods: This retrospective study reviewed total 340 patients with urothelial carcinoma of bladder who received RC between November 1996 and December 2018. The patients were divided into 2 groups by age, 307 patients aged 70–79 and 33 patients aged above 80. Baseline characteristics, perioperative outcomes and early complication were compared between the 2 groups. Kaplan–Meier (K-M) survival analysis was used to estimate RFS, CSS, OS, and multivariable Cox proportional hazard models were used to identify factors predicting RFS, CSS, OS. Results: The results of both groups did not statistically differ from each other in most clinicopathologic baseline characteristics and perioperative information. Both groups showed similar 30-day complication rates (59.3% vs. 60.3%, p=0.210). K-M showed 3-year survival rate, RFS was shorter in oldest-old group (41.4% vs. 56.7%) but not statistically different (p=0.063). Oldest-old group showed similar 3-year CSS (78.1% vs. 74.6%, p=0.779) but worse OS (51% vs. 58%, p=0.047) compared with the old group. Common factor affecting RFS, CSS, and OS were T stage and N stage (all p<0.05). Age is not factor affecting RFS, CSS, and OS. Conclusions Oldest-old who received RC had similar perioperative, oncologic outcome and complication compared with the seventies. RC could be considered treatment option for selected oldest-old patients.

Objective: : Nontraumatic subdural hematoma (SDH) is a common disease, and spinal cerebrospinal fluid (CSF) leakage is a possible etiology of unknown significance, which is commonly investigated by several invasive studies. This study demonstrates that heavily T2-weighted magnetic resonance myelography (HT2W-MRM) is a safe and clinically effective imaging modality for detecting CSF leakage in patients with nontraumatic SDH. Methods: : All patients who underwent HT2W-MRM for nontraumatic SDH workup at our institution were searched and enrolled in this study. Several parameters were measured and analyzed, including patient demographic data, initial modified Rankin Scale (mRS) score upon presentation, SDH bilaterality, hematoma thickness upon presentation, CSF leakage sites, treatment modalities, followup hematoma thickness, and follow-up mRS score. Results: : Forty patients were identified, of which 22 (55.0%) had CSF leakage at various spinal locations. Five patients (12.5%) showed no change in mRS score, whereas the remaining (87.5%) showed decreases in follow-up mRS scores. In terms of the overall hematoma thickness, four patients (10.0%) showed increased thickness, two (5.0%) showed no change, 32 (80.0%) showed decreased thickness, and two (5.0%) did not undergo follow-up imaging for hematoma thickness measurement. Conclusion : HT2W-MRM is not only safe but also clinically effective as a primary diagnostic imaging modality to investigate CSF leakage in patients with nontraumatic SDH. Moreover, this study suggests that CSF leakage is a common etiology for nontraumatic SDH, which warrants changes in the diagnosis and treatment strategies.

Background: We aimed to analyze outcomes of clipping and coiling in treating unruptured intracranial aneurysms (UIAs) in elderly patients and to identify the age at which perioperative risk increases based on national cohort data in South Korea. Methods: The incidence of perioperative intracranial hemorrhage (ICRH), perioperative cerebral infarction (CI), mortality, and moderate to severe disability data of the patients who underwent coiling or clipping for UIAs were retrieved. Estimated breakpoint (EBP) was calculated to identify the age at which the risk of treatment increases. Results: A total of 38,207 patients were treated for UIAs. Among these, 22,093 (57.8%) patients underwent coiling and 16,114 (42.2%) patients underwent clipping. The incidence of ICRH, requiring a secondary operation, within 3 months in patients ≥ 65 years that underwent coiling and clipping was 1.13% and 4.81%, respectively, and that of both groups assessed were significantly higher in patients ≥ 75 years (coiling, P = 0.013, relative risk (RR) 1.81; clipping, P = 0.015) than younger patients. The incidence of CI within 3 months in patients aged ≥ 65 was 13.90% and 9.19% in the coiling and clipping groups, respectively. The incidence of CI after coiling in patients aged ≥ 75 years (P < 0.001, RR 1.96) and after clipping in patients aged ≥ 70 years (P < 0.001, RR 1.76) was significantly higher than that in younger patients. The mortality rates within 1 year in patients with perioperative ICRH or CI were 2.41% and 3.39% for coiling and clipping groups, respectively, in patients ≥ 65. These rates increased significantly at age 70 in the coiling group and at age 75 for the clipping group (P = 0.012 and P < 0.001, respectively). Conclusion The risk of treatment increases with age, and this risk increases dramatically in patients aged ≥ 70 years. Therefore, the treatment decisions in patients aged ≥ 70 years should be made with utmost care.