Efficacy of recombinant Bacillus Calmette-Guérin containing dltA in in vivo three-dimensional bio-printed bladder cancer-on-a-chip and ex vivo orthotopic mouse model

최중원,정태영,김정훈,맹세정,강수정,김미리내,최영욱,최세영,김성환,장인호 대한비뇨의학회 2023 Investigative and Clinical Urology Vol.64 No.3

Purpose: We investigated the efficacy and optimal dosage of recombinant Bacillus Calmette-Guérin-dltA (rBCG-dltA) in a high-throughput 3D bio-printed bladder cancer-on-a-chip (BCOC) and orthotopic bladder cancer mouse model. Materials and Methods: We fabricated high-throughput BCOC with microfluidic systems, enabling efficient drug screening. The efficacy of rBCG-dltA was evaluated using BCOC by the cell viability assay, monocyte migration assay, and measuring cytokine levels. The anti-tumor effect was compared using the orthotopic bladder cancer mouse model. Results: The cell proliferation rates of T24 and 253J bladder cancer cell lines (mean±standard error) were measured at three days after treatment. In T24 cell line, there was significantly decreased T24 cells compared to control at rBCG 1 multiplicity of infection (MOI) and 10 MOI (30 MOI: 63.1±6.4, 10 MOI: 47.4±5.2, 1 MOI: 50.5±7.5, control: 100.0±14.5, p<0.05). In 253J cell line, a statistically significant decrease in 253J cell count compared to control and mock BCG 30 MOI (30 MOI: 11.2±1.3, 10 MOI: 22.5±2.3, 1 MOI: 39.4±4.7, Mock: 54.9±10.8, control: 100.0±5.6, p<0.05). The migration rates of THP-1 cells showed increased patterns after rBCG-dltA treatment in BCOC. The concentration of tumor necrosis factor-α and interleukin-6 after rBCG-dltA 30 MOI treatment was higher than control in T24 and 253J cell line. Conclusions: In conclusion, rBCG-dltA has the potential to have better anti-tumor activity and immunomodulatory effects than BCG. Furthermore, high-throughput BCOCs have potential to reflect the bladder cancer microenvironment.

[청춘 스케치] 그래도 사랑은 남으리

최중원 샘터사 2012 월간 샘터 Vol.507 No.-

Febrile Urinary Tract Infection After Prostate Biopsy and Quinolone Resistance

최중원,김태형,장인호,김경도,문영태,명순철,김진욱,김민수,권종규 대한비뇨의학회 2014 Investigative and Clinical Urology Vol.55 No.10

Purpose: Complications after prostate biopsy have increased and various causes havebeen reported. Growing evidence of increasing quinolone resistance is of particularconcern. In the current retrospective study, we evaluated the incidence of infectiouscomplications after prostate biopsy and identified the risk factors. Materials and Methods: The study population included 1,195 patients who underwenta prostate biopsy between January 2007 and December 2012 at Chung-Ang UniversityHospital. Cases of febrile UTI that occurred within 7 days were investigated. Clinicalinformation included age, prostate-specific antigen, prostate volume, hypertension,diabetes, body mass index, and biopsy done in the quinolone-resistance era. Patientsreceived quinolone (250 mg intravenously) before and after the procedure, and quinolone(250 mg) was orally administered twice daily for 3 days. We used univariate andmultivariate analysis to investigate the predictive factors for febrile UTI. Results: Febrile UTI developed in 39 cases (3.1%). Core numbers increased from 2007(8 cores) to 2012 (12 cores) and quinolone-resistant bacteria began to appear in 2010(quinolone-resistance era). In the univariate analysis, core number≥12 (p=0.024),body mass index (BMI)>25 kg/m2 (p=0.004), and biopsy done in the quinolone-resistanceera (p=0.014) were significant factors. However, in the multivariate analysis adjustedfor core number, the results were not significant, with the exception of BMI>25kg/m2 (p=0.011) and biopsy during the quinolone-resistance era (p=0.035), which weresignificantly associated with febrile UTI. Conclusions: Quinolone resistance is the main cause of postbiopsy infections in ourcenter. We suggest that further evaluation is required to validate similar trends. Novelstrategies to find alternative prophylactic agents are also necessary.

Contemporary Management of Small Renal Masses by Urologic Oncologists: A 2022 Korean Renal Cancer Study Group Practice Pattern Survey

최중원,송채린,서준교,강민용,최창일,육형동,이찬호,김정권,조정기,함원식,황의창,정창욱,고영휘,박재영,서성일,박병관,정진수,곽철,홍성후 대한비뇨기종양학회 2023 대한비뇨기종양학회지 Vol.21 No.1

Purpose: Increased abdominal imaging brought about an explosive increase in the incidental detection of small renal masses (SRMs). In the absence of optimal guidelines for health screening, as well as subsequent diagnostic and therapeutic action plans, incidentally detected SRMs may likewise increasingly become a dilemma, especially in an aging society. In the current study, we aimed to describe the current practice patterns for incidentally detected SRMs among urologic oncologists and to identify key indicators in action plans for active surveillance. Materials and Methods: A survey containing 18 questions on SRM management patterns was designed. In June 2022, an online survey was sent to all 711 active members of the Korean Urological Oncology Society via email. After response collection, a consensus meeting of the Korean Renal Cancer Study Group, which 19 specialists attended, was held to analyze the results. Results: In total, 176 responses from participants practicing in an academic setting were obtained (24.8%, 176 of 711). Regarding the age of patients with SRMs, 42.6% (n=72) responded that they would recommend diagnostic evaluation and definitive treatment for anyone under 80 years of age as long as the patient was healthy. The most commonly used target indicators for surveillance termination were a tumor growth rate above a certain velocity (57.9%, n=102) and size increase above a certain diameter (36.9%, n=65). Renal mass biopsy was recommended in very select cases (<10% of all patients) by most respondents (53.4%, n=94), followed by “not using it at all” in 25.6% (n=45). Conclusions: We described the current practice patterns for incidentally detected SRMs among urologic oncologists and identified key indicators in action plans for active surveillance. This survey provided robust information, empowering physicians with a detailed knowledge of practice patterns and valuable insights on SRMs.

Learning curve of various type of male urethroplasty

최중원,이충언,성현환 대한비뇨의학회 2020 Investigative and Clinical Urology Vol.61 No.5

Purpose: To determine the number of cases required to achieve a specified recurrence-free rate (>80%) among urethroplasty types. Materials and Methods: A retrospective analysis of consecutive patients, who underwent urethroplasty performed by a single surgeon between April 2013 and January 2019, was conducted. Urethroplasty subtypes were divided according to stricture location: penile, bulbar, and posterior. If there was no recurrence for >6 months after surgery, the surgery was considered to be a success. The average success rates among quintile groups were compared to determine the learning curve for each type. Results: Of 150 patients who underwent urethroplasty, 112 were included in this study. The overall success rate was 89.7% in penile, 97.8% in bulbar, and 74.1% in posterior urethroplasty. Bulbar urethroplasty reached the target success rate in the first quintile group (1–9 cases). Penile urethroplasty also achieved the target success rate in the first quintile group (1–8 cases), and the success rate gradually increased until the fifth quintile group (32–39 cases). In posterior urethroplasty, the target success rate was achieved in the fifth quintile group (20–27 cases). Conclusions: Bulbar urethroplasty had the fastest learning curve, and posterior urethroplasty the slowest.

Correlation between Gleason score distribution and Prostate Health Index in patients with prostate-specific antigen values of 2.5–10 ng/mL

최중원,강민용,성현환,전황균,정병창,서성일,전성수,이현무 대한비뇨의학회 2020 Investigative and Clinical Urology Vol.61 No.6

Purpose: To determine the clinical significance and correlation between the Prostate Health Index (PHI) and Gleason score in patients with a prostate-specific antigen (PSA) value of 2.5–10 ng/mL. Materials and Methods: This retrospective analysis included 114 patients who underwent biopsy after completion of the PHI from November 2018 to July 2019. Various parameters such as PSA, PHI, PSA density, free PSA, p2PSA, and %free PSA were collected, and correlations with biopsy Gleason score and cancer detection rates were investigated. Results: Baseline characteristics were comparable between PHI groups (0–26.9 [n=11], 27.0–35.9 [n=17], 36.0–54.9 [n=50], and ≥55.0 [n=36]). A total of 37 patients (32.5%) were diagnosed with prostate cancer, and 28 (24.6%) were diagnosed with clinically significant prostate cancer (CSPC, Gleason score ≥7) after prostate biopsy. The cancer detection rate gradually increased with a corresponding increase in the PHI (18%, 24%, 30%, and 44%, respectively). The same pattern was observed with detecting CSPC (0%, 18%, 26%, and 33%, respectively). There was no CSPC in the groups with PHI <27.0, and Gleason score 7 began to appear in groups with PHI ≥27.0. In particular, patients with Gleason score 8 and 9 were distributed only in the groups with PHI ≥36.0. Conclusions: The diagnostic accuracy of detection of CSPC could be increased when prostate biopsy is performed in patients with a PHI ≥36.0. In this study, there was a clear Gleason score difference when the PHI cutoff value was set to 27.0 or 36.0.

2023 Korean sexually transmitted infections guidelines for non-gonococcal bacterial infection (chlamydia, syphilis, etc.) by the Korean Association of Urogenital Tract Infection and Inflammation

최중원,최진봉,배상락,이찬호,신유섭,유달산,이주용,이승주,이규원 대한비뇨의학회 2024 Investigative and Clinical Urology Vol.65 No.2

Non-gonococcal sexually transmitted infections (STIs) include chlamydia, syphilis, and chancroids. Chlamydia is the most common STI caused by Chlamydia trachomatis and is mainly transmitted through sexual intercourse or vertical transmission at birth. Although symptoms are mostly absent or mild, untreated chlamydial infections in females can lead to pelvic inflammatory disease, chronic pelvic pain, and infertility due to the narrowing of fallopian tubes. Syphilis is caused by Treponema pallidum and is divided into phase I, phase II, latent syphilis, and phase III. The incidence of syphilis, including congenital syphilis, has significantly increased in the United States in recent years. The chronic status of this disease can significantly increase morbidity and potentially affect almost all body organs, which, in rare cases, can lead to death. Additionally, untreated maternal syphilis can lead to fetal death and fatal congenital infections in newborns. Chancroid is an STI caused by Haemophilus ducreyi, and its prevalence is gradually decreasing in Korea and worldwide. The symptoms include shallow genital ulcers with suppurative granulomatous inflammation and tender inguinal lymphadenopathy. Chancroids can be differentiated from syphilitic chancres based on their appearance. In contrast to painless chancres, chancroids are painful. Ureaplasma urealyticum, Ureaplasma parvum, and Mycoplasma hominis are considered symbiotic bacteria. Infections caused by these bacteria are usually not considered STIs and do not require treatment unless they are suspected of being associated with infertility. This article presents the 2023 Korean STI guidelines for non-gonococcal bacterial infections.

Prognostic Significance of Systemic Inflammatory Response in Patients with Synchronous and Metachronous Metastatic Renal Cell Carcinoma Receiving First-Line Tyrosine Kinase Inhibitors

최중원,김태진,성현환,전황균,정병창,전성수,이현무,최한용,강민용,서성일 대한비뇨기종양학회 2019 대한비뇨기종양학회지 Vol.17 No.3

Purpose: To determine whether systemic inflammatory response (SIR), particularly platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR), has different prognostic role between patients with metastatic renal cell carcinoma (mRCC) receiving first-line tyrosine kinase inhibitors (TKI). Materials and Methods: We retrospectively reviewed 547 patients with mRCC who were diagnosed and treated with a first-line TKI between 2007 and 2015. The primary endpoint was overall survival (OS) and secondary endpoint was progression-free survival (PFS). We evaluated differences in survival outcomes according to SIR and identified predictors of OS and PFS. Results: In synchronous mRCC, patients with a higher PLR had significantly worse OS and PFS. Moreover, a higher NLR was also associated with both worse OS and PFS in these patients. However, PLR was not associated with either OS or PFS in metachronous mRCC patients. While metachronous mRCC patients with a higher NLR had worse OS compared to those with lower NLR, there was no difference in PFS according to the status of NLR. On multivariate analysis, PLR was identified as predictive factor for OS (hazard ratio [HR], 1.55) as well as PFS (HR, 1.39) in patients with synchronous mRCC, but not in patients with metachronous mRCC. Additionally, higher NLR was also remained as predictive factor of both OS (HR, 1.83) and PFS (HR, 1.57) in patients with synchronous mRCC. Conclusions: Our study indicates that simple biomarkers of SIR, particularly PLR and NLR, can be more useful predictors of survival outcomes in patients with synchronous mRCC rather than metachronous mRCC.

Prognostic Significance of Systemic Inflammatory Response in Patients with Synchronous and Metachronous Metastatic Renal Cell Carcinoma Receiving First-Line Tyrosine Kinase Inhibitors

Joongwon Choi(최중원),Tae Jin Kim(김태진),Hyun Hwan Sung(성현환),Hwang Gyun Jeon(전황균),Byong Chang Jeong(정병창),Seong Soo Jeon(전성수),Hyun Moo Lee(이현무),Han Yong Choi(최한용),Minyong Kang(강민용),Seong Il Seo(서성일) 대한비뇨기종양학회 2019 대한비뇨기종양학회지 Vol.17 No.3

Purpose: To determine whether systemic inflammatory response (SIR), particularly platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR), has different prognostic role between patients with metastatic renal cell carcinoma (mRCC) receiving first-line tyrosine kinase inhibitors (TKI). Materials and Methods: We retrospectively reviewed 547 patients with mRCC who were diagnosed and treated with a first-line TKI between 2007 and 2015. The primary endpoint was overall survival (OS) and secondary endpoint was progression-free survival (PFS). We evaluated differences in survival outcomes according to SIR and identified predictors of OS and PFS. Results: In synchronous mRCC, patients with a higher PLR had significantly worse OS and PFS. Moreover, a higher NLR was also associated with both worse OS and PFS in these patients. However, PLR was not associated with either OS or PFS in metachronous mRCC patients. While metachronous mRCC patients with a higher NLR had worse OS compared to those with lower NLR, there was no difference in PFS according to the status of NLR. On multivariate analysis, PLR was identified as predictive factor for OS (hazard ratio [HR], 1.55) as well as PFS (HR, 1.39) in patients with synchronous mRCC, but not in patients with metachronous mRCC. Additionally, higher NLR was also remained as predictive factor of both OS (HR, 1.83) and PFS (HR, 1.57) in patients with synchronous mRCC. Conclusions: Our study indicates that simple biomarkers of SIR, particularly PLR and NLR, can be more useful predictors of survival outcomes in patients with synchronous mRCC rather than metachronous mRCC.

Immunotherapeutic effects of recombinant Bacillus Calmette–Guérin containing sic gene in ex vivo and in vivo bladder cancer models

김정훈,최중원,김미리내,강수정,최영욱,최세영,김성환,장인호 대한비뇨의학회 2022 Investigative and Clinical Urology Vol.63 No.2

Purpose: The recombinant Bacillus Calmette–Guérin (BCG) containing the streptococcal inhibitor of the complement gene (rBCG-sic) may be more resistant to antimicrobial peptides and improve internalization; therefore, it can enhance the immunotherapeutic effect of the BCG. Here we determined the optimal dose of rBCG-sic and compared its effectiveness with that of BCG. Materials and Methods: We fabricated a high-throughput 3D-bioprinted bladder cancer-on-a-chip (BCOC) and used it to evaluate the effectiveness of the rBCG-sic in terms of cell viability, cell migration, and cytokine concentrations. Using an orthotopic mouse model, we evaluated its anticancer effect and toxicity via bioluminescence imaging. Results: T24 cell viability was decreased after treatment with rBCG-sic 30 multiplicities of infection (MOI) versus the same dosage of mock BCG (42.8%±6.4% vs. 75.7%±6.6%, p<0.05). THP-1 cell migration was positively correlated with rBCG-sic concentration (2.42-fold at 30MOI, p<0.01). The interleukin-6 concentration of rBCG-sic 30MOI was significantly higher than that of mock BCG 30MOI (11.2±1.3 pg/mL vs. 6.7±0.6 pg/mL, p<0.05). In the orthotopic bladder cancer mouse model, lower tumor volume was observed in the rBCG-sic 30MOI group than in the BCG 30MOI group after 10 days of treatment (p<0.05). Conclusions: We concluded that rBCG-sic is a useful tool for overcoming BCG unresponsiveness in non-muscle invasive bladder cancer. Additionally, high-throughput BCOC with a microfluidic system can successfully reflect the bladder cancer microenvironment.