1.Oncological Outcomes in Men with Metastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide with versus without Confirmatory Bone Scan
Chang Wook JEONG ; Jang Hee HAN ; Dong Deuk KWON ; Jae Young JOUNG ; Choung-Soo KIM ; Hanjong AHN ; Jun Hyuk HONG ; Tae-Hwan KIM ; Byung Ha CHUNG ; Seong Soo JEON ; Minyong KANG ; Sung Kyu HONG ; Tae Young JUNG ; Sung Woo PARK ; Seok Joong YUN ; Ji Yeol LEE ; Seung Hwan LEE ; Seok Ho KANG ; Cheol KWAK
Cancer Research and Treatment 2024;56(2):634-641
Purpose:
In men with metastatic castration-resistant prostate cancer (mCRPC), new bone lesions are sometimes not properly categorized through a confirmatory bone scan, and clinical significance of the test itself remains unclear. This study aimed to demonstrate the performance rate of confirmatory bone scans in a real-world setting and their prognostic impact in enzalutamide-treated mCRPC.
Materials and Methods:
Patients who received oral enzalutamide for mCRPC during 2014-2017 at 14 tertiary centers in Korea were included. Patients lacking imaging assessment data or insufficient drug exposure were excluded. The primary outcome was overall survival (OS). Secondary outcomes included performance rate of confirmatory bone scans in a real-world setting. Kaplan-Meier analysis and multivariate Cox regression analysis were performed.
Results:
Overall, 520 patients with mCRPC were enrolled (240 [26.2%] chemotherapy-naïve and 280 [53.2%] after chemotherapy). Among 352 responders, 92 patients (26.1%) showed new bone lesions in their early bone scan. Confirmatory bone scan was performed in 41 patients (44.6%), and it was associated with prolonged OS in the entire population (median, 30.9 vs. 19.7 months; p < 0.001), as well as in the chemotherapy-naïve (median, 47.2 vs. 20.5 months; p=0.011) and post-chemotherapy sub-groups (median, 25.5 vs. 18.0 months; p=0.006). Multivariate Cox regression showed that confirmatory bone scan performance was an independent prognostic factor for OS (hazard ratio 0.35, 95% confidence interval, 0.18 to 0.69; p=0.002).
Conclusion
Confirmatory bone scan performance was associated with prolonged OS. Thus, the premature discontinuation of enzalutamide without confirmatory bone scans should be discouraged.
2.Effectiveness of Malaria Antibody Test for Screening Blood Donors
Jungwon KANG ; Jaehyun KIM ; Jaesook LEE ; Deuk Yeong KO ; Hwang Min KIM ; Kyoung Young CHOI
Korean Journal of Blood Transfusion 2023;34(1):21-25
The Republic of Korea has been using malaria antibody assays to screen blood donors and reduce the risk of transfusion-transmitted malaria (TTM). This study examined the effectiveness of the current malaria antibody test for screening blood donors and calculated the positive predictive value (PPV) with the real-time polymerase chain reaction (RT-PCR) as the reference. The reactive rate and PPV of the malaria antibody screening assay during particular period from 2020 to 2021 were 0.82% (248/30,309) and 0.40% (1/248), respectively. The low PPV of current malaria antibody screening in blood donors suggests that the effectiveness of this test is limited in terms of balancing blood safety and supply in low-prevalence situations.
3.Comparison of the prevalence and histology between primary benign bladder tumors and recurrent benign lesions after transurethral resection of malignant bladder tumors
Jae Jin BAEK ; Yong Deuk SEO ; Dong Ha KIM ; Won Tae SEO ; Su Hwan KANG ; Taek Sang KIM ; Bong Kwon CHUN
Kosin Medical Journal 2023;38(1):43-49
Background:
Benign bladder tumors are rare disease entities, and insufficient studies have assessed their epidemiological characteristics. The authors investigated the prevalence of benign bladder tumors by retrospectively investigating pathology reports of transurethral resection of bladder tumor (TURBT) procedures over the past 20 years.
Methods:
We analyzed 1,674 pathology reports of TURBT conducted in 1,160 patients from January 1, 2000, to April 30, 2022. The prevalence of benign tumors and histological classification according to the presence of primary (group 1) and recurrent (group 2) bladder lesions were retrospectively investigated.
Results:
The mean age of patients was 65.2±11.5 years, and 1,284 cases (79.1%) were in men. Benign bladder tumors comprised 278 cases (248 patients) accounting for about 17.1% of the total TURBT cases (278/1,624). Furthermore, 184 patients (16.0%, 184/1,147) belonged to group 1 and 78 patients (27.4%, 78/285) belonged to group 2. Among all benign lesions that underwent TURBT, cystitis was the most common (41.0%, 114/278), and this rate was higher in group 2 (64/184 [34.8%] vs. 50/94 [53.2%], p<0.001). The prevalence of non-neoplastic lesions was higher in group 1 (44/184 [23.9] vs. 11/94 [11.7%], p<0.001). There was no difference in the prevalence of noninvasive urothelial neoplasms between the two groups (22/184 [12.0%] vs. 8/94 [8.5%], p=0.86).
Conclusions
The probability of benign lesions in TURBT was 17.1%, among which cystitis was the most common. When TURBT was performed for recurrent lesions, the frequency of benign tumors was higher than that of primary benign bladder tumors.
4.Apalutamide for metastatic castration-sensitive prostate cancer: final analysis of the Asian subpopulation in the TITAN trial.
Byung Ha CHUNG ; Jian HUANG ; Hiroji UEMURA ; Young Deuk CHOI ; Zhang-Qun YE ; Hiroyoshi SUZUKI ; Taek Won KANG ; Da-Lin HE ; Jae Young JOUNG ; Sabine D BROOKMAN-MAY ; Sharon MCCARTHY ; Amitabha BHAUMIK ; Anildeep SINGH ; Suneel MUNDLE ; Simon CHOWDHURY ; Neeraj AGARWAL ; Ding-Wei YE ; Kim N CHI ; Hirotsugu UEMURA
Asian Journal of Andrology 2023;25(6):653-661
The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial showed improvement in overall survival (OS) and other efficacy endpoints with apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer, a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation. Event-driven endpoints were OS, and time from randomization to initiation of castration resistance, prostate-specific antigen (PSA) progression, and second progression-free survival (PFS2) on first subsequent therapy or death. Efficacy endpoints were assessed using the Kaplan-Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity. Participating Asian patients received once-daily apalutamide 240 mg ( n = 111) or placebo ( n = 110) plus ADT. After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide, apalutamide reduced the risk of death by 32% (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.42-1.13), risk of castration resistance by 69% (HR: 0.31; 95% CI: 0.21-0.46), PSA progression by 79% (HR: 0.21; 95% CI: 0.13-0.35) and PFS2 by 24% (HR: 0.76; 95% CI: 0.44-1.29) relative to placebo. The outcomes were comparable between subgroups with low- and high-volume disease at baseline. No new safety issues were identified. Apalutamide provides valuable clinical benefits to Asian patients with mCSPC, with an efficacy and safety profile consistent with that in the overall patient population.
Male
;
Humans
;
Prostatic Neoplasms/pathology*
;
Androgen Antagonists/therapeutic use*
;
Prostate-Specific Antigen
;
Castration
;
Prostatic Neoplasms, Castration-Resistant/drug therapy*
5.MHY2251, a New SIRT1 Inhibitor, Induces Apoptosis via JNK/p53 Pathway in HCT116 Human Colorectal Cancer Cells
Yong Jung KANG ; Young Hoon KWON ; Jung Yoon JANG ; Jun Ho LEE ; Sanggwon LEE ; Yujin PARK ; Hyung Ryong MOON ; Hae Young CHUNG ; Nam Deuk KIM
Biomolecules & Therapeutics 2023;31(1):73-81
Sirtuins (SIRTs) belong to the nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylase family. They are key regulators of cellular and physiological processes, such as cell survival, senescence, differentiation, DNA damage and stress response, cellular metabolism, and aging. SIRTs also influence carcinogenesis, making them potential targets for anticancer therapeutic strategies. In this study, we investigated the anticancer properties and underlying molecular mechanisms of a novel SIRT1 inhibitor, MHY2251, in human colorectal cancer (CRC) cells. MHY2251 reduced the viability of various human CRC cell lines, especially those with wild-type TP53. MHY2251 inhibited SIRT1 activity and SIRT1/2 protein expression, while promoting p53 acetylation, which is a target of SIRT1 in HCT116 cells. MHY2251 treatment triggered apoptosis in HCT116 cells. It increased the percentage of late apoptotic cells and the sub-G1 fraction (as detected by flow cytometric analysis) and induced DNA fragmentation. In addition, MHY2251 upregulated the expression of FasL and Fas, altered the ratio of Bax/Bcl-2, downregulated the levels of pro-caspase-8, -9, and -3 proteins, and induced subsequent poly(ADP-ribose) polymerase cleavage. The induction of apoptosis by MHY2251 was related to the activation of the caspase cascade, which was significantly attenuated by pre-treatment with ZVAD-FMK, a pan-caspase inhibitor. Furthermore, MHY2251 stimulated the phosphorylation of c-Jun N-terminal kinase (JNK), and MHY2251-triggered apoptosis was blocked by pre-treatment with SP600125, a JNK inhibitor. This finding indicated the specific involvement of JNK in MHY2251-induced apoptosis. MHY2251 shows considerable potential as a therapeutic agent for targeting human CRC via the inhibition of SIRT1 and activation of JNK/p53 pathway.
6.Phosphodiesterase-5 Inhibitor Use in Robot Assisted Radical Prostatectomy Patients Is Associated with Reduced Risk of Death: A Propensity Score Matched Analysis of 1,058 Patients
Jongsoo LEE ; Hye Rim KIM ; Ji Eun HEO ; Won Sik JANG ; Kwang Suk LEE ; Sung Ku KANG ; Hyunho HAN ; Young Deuk CHOI
The World Journal of Men's Health 2023;41(4):892-899
Purpose:
We investigated whether the use of a phosphodiesterase-5 inhibitor (PDE5i) after robot assited radical prostatectomy has a survival benefit over non-use patients because there are controversial results on the association between PDE5i use and survival outcomes for prostate cancer patients in literature.
Materials and Methods:
We designed a retrospective, matched, large-sample cohort study of 5,545 patients who underwent robot assisted radical prostatectomy (RARP) during 2013–2021 in a single institute. The exclusion criteria was patients who were aged >70 years at surgery, American Society of Anesthesiologists (ASA) physical status classification grade 4 or 5, history of other malignancies, patients who started PDE5i 6 months after survery and patients with follow up period less than 24 months after surgery. Among the 1,843 included patients, 1,298 were PDE5i users, and 545 were PDE5i non-users. We performed propensity score matching (PSM) of PDE5i users (n=529) with non-users (n=529) by adjusting for the variables of age, Gleason grade group, pathological T stage, preoperative ASA physical status grade, and International Index of Erectile Function score.
Results:
There were no significant difference in patient characteristics according to PSM. Kaplan–Meier curve revealed the difference of overall survival for PDE5i users and non-users (clustered log-rank test p<0.05). In a stratified Cox regression analysis, PDE5i use after RARP was associated with improved overall survival and reduced risk of death (hazard ratio 0.43; confidence interval 0.24–0.79; p=0.007). The limitation of this study was that the indication for the prescription of PDE5i was not given.
Conclusions
PDE5i administration after RARP were associated with overall survival of patients with prostate cancer. A further randomized control trial may reveal whether routine use of PDE5i after prostatectomy can improve survival of prostate cancer patient.
7.Immune Responses to Plant-Derived Recombinant Colorectal Cancer Glycoprotein EpCAM-FcK Fusion Protein in Mice
Chae-Yeon LIM ; Deuk-Su KIM ; Yangjoo KANG ; Ye-Rin LEE ; Kibum KIM ; Do Sun KIM ; Moon-Soo KIM ; Kisung KO
Biomolecules & Therapeutics 2022;30(6):546-552
Epidermal cell adhesion molecule (EpCAM) is a tumor-associated antigen (TAA), which has been considered as a cancer vaccine candidate. The EpCAM protein fused to the fragment crystallizable region of immunoglobulin G (IgG) tagged with KDEL endoplasmic reticulum (ER) retention signal (EpCAM-FcK) has been successfully expressed in transgenic tobacco (Nicotiana tabacum cv. Xanthi) and purified from the plant leaf. In this study, we investigated the ability of the plant-derived EpCAM-FcK (EpCAM-FcKP ) to elicit an immune response in vivo. The animal group injected with the EpCAM-FcKP showed a higher differentiated germinal center (GC) B cell population (~9%) compared with the animal group injected with the recombinant rhEpCAM-Fc chimera (EpCAM-FcM ). The animal group injected with EpCAM-FcKP (~42%) had more differentiated T follicular helper cells (Tfh) than the animal group injected with EpCAM-FcM (~7%). This study demonstrated that the plant-derived EpCAM-FcK fusion antigenic protein induced a humoral immune response in mice.
8.Laparoscopic pancreaticoduodenectomy with excision of aberrant right hepatic artery after preoperative segmental embolization in mid-bile duct cancer
Yoonwon KOOK ; Munseok CHOI ; Jung Yup PARK ; Ho Kyoung HWANG ; Woo Jung LEE ; Man-Deuk KIM ; Chang Moo KANG
Journal of Minimally Invasive Surgery 2021;24(2):104-108
Laparoscopic pancreaticoduodenectomy has proven to be a safe and effective alternative to open pancreati coduodenectomy with similar oncologic outcomes. Cases including excision of the hepatic artery with or without reconstruction during pancreaticoduodenectomy have been reported for periampullary cancer. Here we present a case of an 82-year-old patient who underwent laparoscopic pancreaticoduodenectomy following preoperative arterial embolization of an aberrant right hepatic artery arising from the superior mesenteric artery.
9.Trends in epidemiologic characteristics of end-stage renal disease from 2019 Korean Renal Data System (KORDS)
Yu Ah HONG ; Tae Hyun BAN ; Chae-Yeong KANG ; Sun Deuk HWANG ; Sun Ryoung CHOI ; Hajeong LEE ; Hee-Yeon JUNG ; Kyeongmin KIM ; Young Eun KWON ; Su Hyun KIM ; Tae Hee KIM ; Ho-Seok KOO ; Chang-Yun YOON ; Kiwon KIM ; Jongha PARK ; Yong Kyun KIM
Kidney Research and Clinical Practice 2021;40(1):52-61
Background:
The Korean Society of Nephrology (KSN) has maintained a nationwide end-stage renal disease (ESRD) registry data from Korean Renal Data System (KORDS) since 1985, as the representative registry of ESRD patients in Korea. This review is aimed to update the status of domestic ESRD and to provide evidence on the direction of dialysis therapy.
Methods:
The KORDS Committee of KSN has collected data on dialysis centers and patients through an online registry program, and the data from 1986 to 2019 were analyzed.
Results:
The incidence and prevalence of ESRD patients in Korea are increasing. The ESRD population numbered more than 100,000 in 2019, doubling during the 10 years since 2010. The proportion of diabetes mellitus as a major cause of ESRD seems to have reached a plateau. The increasing number of elderly dialysis patients is a constant trend, with more than half for the proportion of patients older than 65 years old in 2019. All-cause mortality decreased for the last approximately 20 years, regardless of sex, age, and cause of ESRD. The 5-year patient survival rate in both hemodialysis and peritoneal dialysis increased from 2001 to 2013. Since 2013, the patient survival rates in peritoneal dialysis were similar to those in hemodialysis. Cardiovascular complications were the leading cause of death in ESRD patients.
Conclusions
The incidence and prevalence of Korean ESRD patients have increased over time, although patient survival has also steadily increased. The establishment of a surveillance method to address the major cause of mortality in ESRD patients will help improve outcomes.
10.Laparoscopic pancreaticoduodenectomy with excision of aberrant right hepatic artery after preoperative segmental embolization in mid-bile duct cancer
Yoonwon KOOK ; Munseok CHOI ; Jung Yup PARK ; Ho Kyoung HWANG ; Woo Jung LEE ; Man-Deuk KIM ; Chang Moo KANG
Journal of Minimally Invasive Surgery 2021;24(2):104-108
Laparoscopic pancreaticoduodenectomy has proven to be a safe and effective alternative to open pancreati coduodenectomy with similar oncologic outcomes. Cases including excision of the hepatic artery with or without reconstruction during pancreaticoduodenectomy have been reported for periampullary cancer. Here we present a case of an 82-year-old patient who underwent laparoscopic pancreaticoduodenectomy following preoperative arterial embolization of an aberrant right hepatic artery arising from the superior mesenteric artery.

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