1.Enzalutamide Maintenance Following Docetaxel in Metastatic Castration-Naive Prostate Cancer: A Pilot Feasibility Study
Sung Hee LIM ; Sung Wook CHO ; Jae Hoon CHUNG ; Wan SONG ; Minyong KANG ; Hyun Hwan SUNG ; Hwang Gyun JEON ; Byong Chang JEONG ; Seong Il SEO ; Seong Soo JEON ; Se Hoon PARK
Journal of Urologic Oncology 2024;22(1):29-33
		                        		
		                        			 Purpose:
		                        			To assess the feasibility and short-term efficacy of maintenance enzalutamide following first-line docetaxel plus androgen deprivation therapy (ADT) in patients with high-volume, metastatic castration-naive prostate cancer (mCNPC). 
		                        		
		                        			Materials and Methods:
		                        			The present study included 38 consecutive patients with mCNPC who did not have disease progression with ADT plus docetaxel between October 2022 and October 2023. Patients received a switch maintenance therapy with enzalutamide until progression, unacceptable toxicity, or patient withdrawal. Endpoints included time to prostate-specific antigen (PSA) progression and safety. 
		                        		
		                        			Results:
		                        			Among the 38 patients, the median age was 68 years, and the most frequently observed metastatic site was bone (n=36), followed by lymph nodes (n=28), lung (n=8), and liver (n=1). The median duration of firstline docetaxel was 2.8 months (range, 2.7–5.0 months). At the time of commencing maintenance enzalutamide, the median PSA was 3.2 ng/mL (range, 0.01–258 ng/mL). Maintenance enzalutamide was generally welltolerated. A total of 11 patients (28%) discontinued enzalutamide, and the main reasons included adverse events (prolonged fatigue of grade 1 or 2, n=6), disease progression (n=3) and financial burdens (n=2). Median time to PSA progression was not reached, and 93% were PSA progression-free at 12 months. 
		                        		
		                        			Conclusions
		                        			Maintenance enzalutamide is a feasible treatment option with potential clinical benefit for patients with high-volume mCNPC who were progression-free after first-line ADT+docetaxel. 
		                        		
		                        		
		                        		
		                        	
2.Comparison of Short-Term Outcomes and Safety Profiles between Androgen Deprivation Therapy+Abiraterone/Prednisone and Androgen Deprivation Therapy+Docetaxel in Patients with De Novo Metastatic Hormone-Sensitive Prostate Cancer
Dong Jin PARK ; Tae Gyun KWON ; Jae Young PARK ; Jae Young JOUNG ; Hong Koo HA ; Seong Soo JEON ; Sung-Hoo HONG ; Sungchan PARK ; Seung Hwan LEE ; Jin Seon CHO ; Sung-Woo PARK ; Se Yun KWON ; Jung Ki JO ; Hong Seok PARK ; Sang-Cheol LEE ; Dong Deuk KWON ; Sun Il KIM ; Sang Hyun PARK ; Soodong KIM ; Chang Wook JEONG ; Cheol KWAK ; Seock Hwan CHOI ;
The World Journal of Men's Health 2024;42(3):620-629
		                        		
		                        			 Purpose:
		                        			This study aimed to compare the short-term outcomes and safety profiles of androgen-deprivation therapy (ADT)+abiraterone/prednisone with those of ADT+docetaxel in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). 
		                        		
		                        			Materials and Methods:
		                        			A web-based database system was established to collect prospective cohort data for patients with mHSPC in Korea. From May 2019 to November 2022, 928 patients with mHSPC from 15 institutions were enrolled. Among these patients, data from 122 patients who received ADT+abiraterone/prednisone or ADT+docetaxel as the primary systemic treatment for mHSPC were collected. The patients were divided into two groups: ADT+abiraterone/prednisone group (n=102) and ADT+docetaxel group (n=20). We compared the demographic characteristics, medical histories, baseline cancer status, initial laboratory tests, metastatic burden, oncological outcomes for mHSPC, progression after mHSPC treatment, adverse effects, follow-up, and survival data between the two groups. 
		                        		
		                        			Results:
		                        			No significant differences in the demographic characteristics, medical histories, metastatic burden, and baseline cancer status were observed between the two groups. The ADT+abiraterone/prednisone group had a lower prostate-specific antigen (PSA) progression rate (7.8% vs. 30.0%; p=0.011) and lower systemic treatment discontinuation rate (22.5% vs. 45.0%; p=0.037). No significant differences in adverse effects, oncological outcomes, and total follow-up period were observed between the two groups. 
		                        		
		                        			Conclusions
		                        			ADT+abiraterone/prednisone had lower PSA progression and systemic treatment discontinuation rates than ADT+docetaxel. In conclusion, further studies involving larger, double-blinded randomized trials with extended follow-up periods are necessary. 
		                        		
		                        		
		                        		
		                        	
3.Role of Dedicated Subspecialized Radiologists in Multidisciplinary Team Discussions on Lower Gastrointestinal Tract Cancers
Sun Kyung JEON ; Se Hyung KIM ; Cheong-il SHIN ; Jeongin YOO ; Kyu Joo PARK ; Seung-Bum RYOO ; Ji Won PARK ; Tae-You KIM ; Sae-Won HAN ; Dae-Won LEE ; Eui Kyu CHIE ; Hyun-Cheol KANG
Korean Journal of Radiology 2022;23(7):732-
		                        		
		                        			 Objective:
		                        			To determine the impact of dedicated subspecialized radiologists in multidisciplinary team (MDT) discussions on the management of lower gastrointestinal (GI) tract malignancies. 
		                        		
		                        			Materials and Methods:
		                        			We retrospectively analyzed the data of 244 patients (mean age ± standard deviation, 61.7 ± 11.9 years) referred to MDT discussions 249 times (i.e., 249 cases, as five patients were discussed twice for different issues) for lower GI tract malignancy including colorectal cancer, small bowel cancer, GI stromal tumor, and GI neuroendocrine tumor between April 2018 and June 2021 in a prospective database. Before the MDT discussions, dedicated GI radiologists reviewed all imaging studies again besides routine clinical reading. The referring clinician’s initial diagnosis, initial treatment plan, change in radiologic interpretation compared with the initial radiology report, and the MDT’s consensus recommendations for treatment were collected and compared. Factors associated with changes in treatment plans and the implementation of MDT decisions were analyzed. 
		                        		
		                        			Results:
		                        			Of the 249 cases, radiologic interpretation was changed in 73 cases (29.3%) after a review by dedicated GI radiologists, with 78.1% (57/73) resulting in changes in the treatment plan. The treatment plan was changed in 92 cases (36.9%), and the rate of change in the treatment plan was significantly higher in cases with changes in radiologic interpretation than in those without (78.1% [57/73] vs. 19.9% [35/176], p < 0.001). Follow-up records of patients showed that 91.2% (227/249) of MDT recommendations for treatment were implemented. Multiple logistic regression analysis revealed that the nonsurgical approach (vs. surgical approach) decided through MDT discussion was a significant factor for patients being managed differently than the MDT recommendations (odds ratio, 4.48; p = 0.017). 
		                        		
		                        			Conclusion
		                        			MDT discussion involving additional review of radiology examinations by dedicated GI radiologists resulted in a change in the treatment plan in 36.9% of cases. Changes in treatment plans were significantly associated with changes in radiologic interpretation. 
		                        		
		                        		
		                        		
		                        	
4.Assessment of Image Quality for Selective Intracoronary Contrast-Injected CT Angiography in a Hybrid Angio-CT System: A Feasibility Study in Swine
Seongmin HA ; Sunghee JUNG ; Hyung-Bok PARK ; Sanghoon SHIN ; Reza ARSANJANI ; Youngtaek HONG ; Byoung Kwon LEE ; Yeonggul JANG ; Byunghwan JEON ; Se-Il PARK ; Hackjoon SHIM ; Hyuk-Jae CHANG
Yonsei Medical Journal 2021;62(3):200-208
		                        		
		                        			 Purpose:
		                        			To compare image quality in selective intracoronary contrast-injected computed tomography angiography (SelectiveCTA) with that in conventional intravenous contrast-injected CTA (IV-CTA). 
		                        		
		                        			Materials and Methods:
		                        			Six pigs (35 to 40 kg) underwent both IV-CTA using an intravenous injection (60 mL) and Selective-CTA using an intracoronary injection (20 mL) through a guide-wire during/after percutaneous coronary intervention. Images of the common coronary artery were acquired. Scans were performed using a combined machine comprising an invasive coronary angiography suite and a 320-channel multi-slice CT scanner. Quantitative image quality parameters of CT attenuation, image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), mean lumen diameter (MLD), and mean lumen area (MLA) were measured and compared. Qualitative analysis was performed using intraclass correlation coefficient (ICC), which was calculated for analysis of interobserver agreement. 
		                        		
		                        			Results:
		                        			Quantitative image quality, determined by assessing the uniformity of CT attenuation (399.06 vs. 330.21, p<0.001), image noise (24.93 vs. 18.43, p<0.001), SNR (16.43 vs. 18.52, p=0.005), and CNR (11.56 vs. 13.46, p=0.002), differed significantly between IV-CTA and Selective-CTA. MLD and MLA showed no significant difference overall (2.38 vs. 2.44, p=0.068, 4.72 vs. 4.95, p=0.078).The density of contrast agent was significantly lower for selective-CTA (13.13 mg/mL) than for IV-CTA (400 mg/mL). Agreement between observers was acceptable (ICC=0.79±0.08). 
		                        		
		                        			Conclusion
		                        			Our feasibility study in swine showed that compared to IV-CTA, Selective-CTA provides better image quality and requires less iodine contrast medium. 
		                        		
		                        		
		                        		
		                        	
5.Panel-Reactive and Donor-Specific Antibodies before Lung Transplantation can Affect Outcomes in Korean Patients Receiving Lung Transplantation
Sung Woo MOON ; Moo Suk PARK ; Jin Gu LEE ; Hyo Chae PAIK ; Young Tae KIM ; Hyun Joo LEE ; Samina PARK ; Sun Mi CHOI ; Do Hyung KIM ; Woo Hyun CHO ; Hye Ju YEO ; Seung-il PARK ; Se Hoon CHOI ; Sang-Bum HONG ; Tae Sun SHIM ; Kyung-Wook JO ; Kyeongman JEON ; Byeong-Ho JEONG ; Song Yee KIM ;
Yonsei Medical Journal 2020;61(7):606-613
		                        		
		                        			 Purpose:
		                        			Data on the distribution and impact of panel reactive antibodies (PRA) and donor specific antibodies (DSA) before lung transplantation in Asia, especially multi-center-based data, are limited. This study evaluated the prevalence of and effects of PRA and DSA levels before lung transplantations on outcomes in Korean patients using nationwide multicenter registry data. 
		                        		
		                        			Materials and Methods:
		                        			This study included 103 patients who received a lung transplant at five tertiary hospitals in South Korea between March 2015 and December 2017. Mortality, primary graft dysfunction (PGD), and bronchiolitis obliterans syndrome (BOS) were evaluated. 
		                        		
		                        			Results:
		                        			Sixteen patients had class I and/or class II PRAs exceeding 50%. Ten patients (9.7%) had DSAs with a mean fluorescence intensity (MFI) higher than 1000, six of whom had antibodies with a high MFI (≥2000). DSAs with high MFIs were more frequently observed in patients with high-grade PGD (≥2) than in those with no or low-grade (≤1) PGD. In the 47 patients who survived for longer than 9 months and were evaluated for BOS after the transplant, BOS was not related to DSA or PRA levels. One-year mortality was more strongly related to PRA class I exceeding 50% than that under 50% (0% vs. 16.7%, p=0.007). 
		                        		
		                        			Conclusion
		                        			Preoperative DSAs and PRAs are related to worse outcomes after lung transplantation. DSAs and PRAs should be considered when selecting lung transplant recipients, and recipients who have preoperative DSAs with high MFI values and high PRA levels should be monitored closely after lung transplantation. 
		                        		
		                        		
		                        		
		                        	
6.Node-Positive Bladder Cancer After Neoadjuvant Chemotherapy Followed by Radical Cystectomy: A Single-Center Retrospective Study
Jang Ho CHO ; Ghee-Young KWON ; Minyong KANG ; Hyun Hwan SUNG ; Hwang Gyun JEON ; Byong Chang JEONG ; Seong Il SEO ; Seong Soo JEON ; Hyun Moo LEE ; Han-Yong CHOI ; Su Jin LEE ; Se Hoon PARK
Korean Journal of Urological Oncology 2020;18(3):194-200
		                        		
		                        			Purpose:
		                        			There remains a lot of unmet need to increase understanding of node-positive (ypN+) muscle invasive bladder cancer (MIBC) after neoadjuvant chemotherapy and radical cystectomy to decide the appropriate therapeutics. 
		                        		
		                        			Materials and Methods:
		                        			In a retrospective study using the center cancer chemotherapy registry, we found 113 MIBC patients who were treated with neoadjuvant chemotherapy involving gemcitabine and cisplatin (GP) followed by radical cystectomy between 2010 and 2014. Disease-free survival (DFS) and overall survival (OS) were compared according to the pathologic node positivity (ypN- vs. ypN+). Among a total of 165 patients with MIBC who received neoadjuvant chemotherapy involving GP, 118 underwent radical cystectomy. In 46 patients with ypN+ disease, DFS and OS were evaluated according to administration of adjuvant GP. 
		                        		
		                        			Results:
		                        			After neoadjuvant chemotherapy and radical cystectomy, 41% of patients had ypN+ disease, which showed significantly shorter DFS (median, 7.4 months; 95% confidence interval [CI], 5.3–9.6 months) and OS (median, 20.0 months; 95% CI, 13.4–26.6 months) compared to those with ypN- disease. The patients with ypN+ disease had a high risk of recurrence or death, regardless of the administration of adjuvant chemotherapy or adjuvant regimen. 
		                        		
		                        			Conclusions
		                        			Within the limitations of this retrospective study, MIBC patients with ypN+ disease despite neoadjuvant chemotherapy and radical cystectomy had a poor prognosis. Further studies involving novel, effective adjuvant treatment including immunotherapy agents are needed to reduce the high risk of recurrence or death in these patients.
		                        		
		                        		
		                        		
		                        	
7.Node-Positive Bladder Cancer After Neoadjuvant Chemotherapy Followed by Radical Cystectomy: A Single-Center Retrospective Study
Jang Ho CHO ; Ghee-Young KWON ; Minyong KANG ; Hyun Hwan SUNG ; Hwang Gyun JEON ; Byong Chang JEONG ; Seong Il SEO ; Seong Soo JEON ; Hyun Moo LEE ; Han-Yong CHOI ; Su Jin LEE ; Se Hoon PARK
Korean Journal of Urological Oncology 2020;18(3):194-200
		                        		
		                        			Purpose:
		                        			There remains a lot of unmet need to increase understanding of node-positive (ypN+) muscle invasive bladder cancer (MIBC) after neoadjuvant chemotherapy and radical cystectomy to decide the appropriate therapeutics. 
		                        		
		                        			Materials and Methods:
		                        			In a retrospective study using the center cancer chemotherapy registry, we found 113 MIBC patients who were treated with neoadjuvant chemotherapy involving gemcitabine and cisplatin (GP) followed by radical cystectomy between 2010 and 2014. Disease-free survival (DFS) and overall survival (OS) were compared according to the pathologic node positivity (ypN- vs. ypN+). Among a total of 165 patients with MIBC who received neoadjuvant chemotherapy involving GP, 118 underwent radical cystectomy. In 46 patients with ypN+ disease, DFS and OS were evaluated according to administration of adjuvant GP. 
		                        		
		                        			Results:
		                        			After neoadjuvant chemotherapy and radical cystectomy, 41% of patients had ypN+ disease, which showed significantly shorter DFS (median, 7.4 months; 95% confidence interval [CI], 5.3–9.6 months) and OS (median, 20.0 months; 95% CI, 13.4–26.6 months) compared to those with ypN- disease. The patients with ypN+ disease had a high risk of recurrence or death, regardless of the administration of adjuvant chemotherapy or adjuvant regimen. 
		                        		
		                        			Conclusions
		                        			Within the limitations of this retrospective study, MIBC patients with ypN+ disease despite neoadjuvant chemotherapy and radical cystectomy had a poor prognosis. Further studies involving novel, effective adjuvant treatment including immunotherapy agents are needed to reduce the high risk of recurrence or death in these patients.
		                        		
		                        		
		                        		
		                        	
8.Early Experiences with Nivolumab in Patients with Metastatic Renal Cell Carcinoma and Failed Target Therapy
Jong Hoon LEE ; Minyong KANG ; Jae Hoon CHUNG ; Hyun Hwan SUNG ; Hwang Gyun JEON ; Byung Chang JEONG ; Seong Soo JEON ; Hyun Moo LEE ; Se Hoon PARK ; Binnari KIM ; Ghee Young KWON ; Seong Il SEO
Korean Journal of Urological Oncology 2019;17(2):96-102
		                        		
		                        			
		                        			PURPOSE: The efficacy of nivolumab in metastatic renal cell carcinoma (mRCC) has been proven. However, the nivolumab experience in Korean patients with mRCC is still poorly reported. We report initial experiences with the efficacy and safety of nivolumab in patients with mRCC. MATERIALS AND METHODS: We retrospectively reviewed records for 25 patients with mRCC who had failed targeted therapy and were treated by nivolumab (2 mg/kg, every 2 weeks) at a single institution. The primary endpoint was objective response rate (ORR), and secondary endpoints were progression-free survival (PFS), safety profiles, and ORR in a programmed cell death receptor ligand 1 (PD-L1) expression subgroup. RESULTS: The median age was 60 years and 16 patients (64%) were male. Objective responses were achieved in 8 patients (32.0%) (complete response, 1; partial response, 7). Median PFS was 3.0 months (95% confidence interval, 1.46–4.53). Treatment-related adverse events (AEs) of any grade were observed in 19 patients (76.0%) with 6 (24.0%) experiencing grade 3 to 4 treatment-related AEs. In subgroups by PD-L1 expression levels classified as 1% or greater and less than 1%, ORR was 50% and 0%, respectively. CONCLUSIONS: This study showed the efficacy and safety of initial experiences with nivolumab in Korean patients with mRCC who had failed targeted therapy. Our results were comparable to recent clinical trials on nivolumab in mRCC.
		                        		
		                        		
		                        		
		                        			Antigens, CD274
		                        			;
		                        		
		                        			Carcinoma, Renal Cell
		                        			;
		                        		
		                        			Cell Death
		                        			;
		                        		
		                        			Disease-Free Survival
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Neoplasm Metastasis
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
9.Characteristics of Lung Allocation and Outcomes of Lung Transplant according to the Korean Urgency Status
Woo Sik YU ; Song Yee KIM ; Young Tae KIM ; Hyun Joo LEE ; Samina PARK ; Sun Mi CHOI ; Do Hyung KIM ; Woo Hyun CHO ; Hye Ju YEO ; Seung il PARK ; Se Hoon CHOI ; Sang Bum HONG ; Tae Sun SHIM ; Kyung Wook JO ; Kyeongman JEON ; Byeong Ho JEONG ; Hyo Chae PAIK ; Jin Gu LEE ;
Yonsei Medical Journal 2019;60(10):992-997
		                        		
		                        			
		                        			PURPOSE: We investigated the characteristics of lung allocation and outcomes of lung transplant (LTx) according to the Korean urgency status. MATERIALS AND METHODS: LTx registration in the Korean Organ Transplantation Registry (KOTRY) began in 2015. From 2015 to June 2017, 86 patients who received LTx were enrolled in KOTRY. After excluding one patient who received a heart-lung transplant, 85 were included. Subjects were analyzed according to the Korean urgency status. RESULTS: Except for Status 0, urgency status was classified based on partial pressure of oxygen in arterial blood gas analysis and functional status in 52 patients (93%). The wait time for lung allograft was well-stratified by urgency (Status 0, 46.5±59.2 days; Status 1, 104.4±98.2 days; Status 2 or 3, 132.2±118.4 days, p=0.009). Status 0 was associated with increased operative times and higher intraoperative blood transfusion. Status 0 was associated with prolonged extracorporeal membrane oxygenation use, postoperative bleeding, and longer mechanical ventilation after operation. Survival of Status 0 patients seemed worse than that of non-Status 0 patients, although differences were not significant. CONCLUSION: The Korean urgency classification for LTx is determined by using very limited parameters and may not be a true reflection of urgency. Status 0 patients seem to have poor outcomes compared to the other urgency status patients, despite having the highest priority for donor lungs. Further multi-center and nationwide studies are needed to revise the lung allocation system to reflect true urgency and provide the best benefit of lung transplantation.
		                        		
		                        		
		                        		
		                        			Allografts
		                        			;
		                        		
		                        			Blood Gas Analysis
		                        			;
		                        		
		                        			Blood Transfusion
		                        			;
		                        		
		                        			Classification
		                        			;
		                        		
		                        			Extracorporeal Membrane Oxygenation
		                        			;
		                        		
		                        			Hemorrhage
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Lung Transplantation
		                        			;
		                        		
		                        			Lung
		                        			;
		                        		
		                        			Operative Time
		                        			;
		                        		
		                        			Organ Transplantation
		                        			;
		                        		
		                        			Oxygen
		                        			;
		                        		
		                        			Partial Pressure
		                        			;
		                        		
		                        			Respiration, Artificial
		                        			;
		                        		
		                        			Tissue Donors
		                        			;
		                        		
		                        			Transplants
		                        			
		                        		
		                        	
10.Neutrophil to Lymphocyte Ratio: A Predictive Marker for Treatment Outcomes in Patients With Rectal Cancer Who Underwent Neoadjuvant Chemoradiation Followed by Surgery
Byong Ho JEON ; Ui Sup SHIN ; Sun Mi MOON ; Jung Il CHOI ; Mi Sook KIM ; Kie Hwan KIM ; Se Jin SUNG
Annals of Coloproctology 2019;35(2):100-106
		                        		
		                        			
		                        			PURPOSE: In this study, we investigated the role of neutrophil to lymphocyte ratio (NLR) as a predictor of tumor response and as a prognostic factor in patients with rectal cancer who had undergone curative surgery after neoadjuvant chemoradiation therapy (nCRT). METHODS: Between January 2009 and July 2016, we collected 140 consecutive patients who had undergone curative intent surgery after nCRT due to rectal adenocarcinoma. We obtained the pre- and post-nCRT NLR by dividing the neutrophil count by the lymphocyte count. The cutoff value was obtained using receiver operating characteristic analysis for tumor response and using maximally selected rank analysis for recurrence-free survival (RFS). The relationship among NLR, tumor response, and RFS was assessed by adjusting the possible clinico-pathological confounding factors. RESULTS: The possibility of pathologic complete response (pCR) was significantly decreased in high pre- (>2.77) and postnCRT NLR (>3.23) in univariate regression analysis. In multivariate analysis, high post-nCRT NLR was an independent negative predictive factor for pCR (adjusted odds ratio, 0.365; 95% confidence interval [CI], 0.145–0.918). The 5-year RFS of all patients was 74.6% during the median 37 months of follow-up. Patients with higher pre- (>2.66) and post-nCRT NLR (>5.21) showed lower 5-year RFS rates (53.1 vs. 83.3%, P = 0.006) (69.2 vs. 75.7%, P = 0.054). In multivariate Cox analysis, high pre-nCRT NLR was an independent poor prognostic factor for RFS (adjusted hazard ratio, 2.300; 95% CI, 1.061–4.985). CONCLUSION: Elevated NLR was a negative predictive marker for pCR and was independently associated with decreased RFS. For confirmation, a large-scale study with appropriate controls is needed.
		                        		
		                        		
		                        		
		                        			Adenocarcinoma
		                        			;
		                        		
		                        			Biomarkers
		                        			;
		                        		
		                        			Chemoradiotherapy
		                        			;
		                        		
		                        			Follow-Up Studies
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Lymphocyte Count
		                        			;
		                        		
		                        			Lymphocytes
		                        			;
		                        		
		                        			Multivariate Analysis
		                        			;
		                        		
		                        			Neutrophils
		                        			;
		                        		
		                        			Odds Ratio
		                        			;
		                        		
		                        			Polymerase Chain Reaction
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Rectal Neoplasms
		                        			;
		                        		
		                        			ROC Curve
		                        			
		                        		
		                        	
            
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