The Efficacy and Safety of a Human Perirenal Adipose TissueDerived Stromal Vascular Fraction in an Interstitial Cystitis Rat Model

BACKGROUND@#Interstitial cystitis (IC) is a chronic and intractable disease that can severely deteriorate patients’ quality of life. Recently, stem cell therapy has been introduced as a promising alternative treatment for IC in animal models. We aimed to verify the efficacy and safety of the human perirenal adipose tissue-derived stromal vascular fraction (SVF) in an IC rat model. @*METHODS@#From eight-week-old female rats, an IC rat model was established by subcutaneous injection of 200 lg of uroplakin3A. The SVF was injected into the bladder submucosal layer of IC rats, and pain scale analysis, awakening cytometry, and histological and gene analyses of the bladder were performed. For the in vivo safety analysis, genomic DNA purification and histological analysis were also performed to check tumorigenicity and thrombus formation. @*RESULTS@#The mean pain scores in the SVF 20 ll group were significantly lower on days 7 and 14 than those in the control group, and bladder intercontraction intervals were significantly improved in the SVF groups in a dose-dependent manner. Regeneration of the bladder epithelium, basement membrane, and lamina propria was observed in the SVF group.In the SVF groups, however, bladder fibrosis and the expression of inflammatory markers were not significantly improved compared to those in the control group. @*CONCLUSION@#This study demonstrated that a perirenal adipose tissue-derived SVF is a promising alternative for the management of IC in terms of improving bladder pain and overactivity.

Real-World Study Evaluating Safety and Effectiveness of Axitinib in Korean Patients with Renal Cell Carcinoma after Failure of One Prior Systemic Therapy / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This post-marketing surveillance (PMS) study was conducted to monitor the usage of axitinib (Inlyta) in clinical practice of Korean patients with advanced renal cell carcinoma (RCC) with disease progression during or after a prior systemic therapy in real world. @*Materials and Methods@#In this multicenter, observational study, patients indicated for oral axitinib 5 mg twice daily as second-line therapy for advanced RCC were followed up under routine clinical practices, and their safety and effectiveness outcomes were collected. @*Results@#Between 2012 and 2021, 125 patients were enrolled, and data from 111 patients were analyzed. Median age was 65 years (range, 30 to 84 years), 81% was male, and 110 (99%) had clear cell RCC. The median daily dose of axitinib was 10 mg (range, 4.36 to 15.95 mg) with a median administration period of 5.6 months (range, 15 to 750 days). Eighty-three percentage of patients experienced any grade of adverse events, 71% of which were related to study treatment, including diarrhea (36%), hypertension (21%), stomatitis (17%), decreased appetite (14%), palmar-plantar erythrodysesthesia syndrome (12%), and asthenia (11%). Most adverse events were generally well tolerated and manageable, with 13% of grade ≥ 3. Axitinib dose reduction was required in 20% of the adverse events and discontinuation in 8%. Median progression-free survival was 12.4 months (95% confidence interval [CI], 9.6 to 18.9). Objective responses were observed in 30% of patients (95% CI, 21 to 39) with 4% of complete response and 26% of partial response. @*Conclusion@#No new safety signal was found in the present PMS study of Korean RCC patients. Axitinib showed consistent outcomes in terms of effectiveness and safety confirming that the drug is a valid option for second-line therapy in patients with advanced RCC in a real-world setting.

Improvement of IgA Nephropathy and Kidney Regeneration by Functionalized Hyaluronic Acid and Gelatin Hydrogel

BACKGROUND@#Immunoglobulin A (IgA) nephropathy (IgAN) is one of an important cause of progressive kidney disease and occurs when IgA settles in the kidney resulted in disrupts kidney’s ability to filter waste and excess water.Hydrogels are promising material for medical applications owing to their excellent adaptability and filling ability. Herein, we proposed a hyaluronic acid/gelatin (CHO-HA/Gel-NH2 ) bioactive hydrogel as a cell carrier for therapeutic kidney regeneration in IgAN. @*METHODS@#CHO-HA/Gel-NH2 hydrogel was fabricated by Schiff-base reaction without any additional crosslinking agents. The hydrogel concentrations and ratios were evaluated to enhance adequate mechanical properties and biocompatibility for further in vivo study. High serum IgA ddY mice kidneys were treated with human urine-derived renal progenitor cells encapsulated in the hydrogel to investigate the improvement of IgA nephropathy and kidney regeneration. @*RESULTS@#The stiffness of the hydrogel was significantly enhanced and could be modulated by altering the concentrations and ratios of hydrogel. CHO-HA/Gel-NH2 at a ratio of 3/7 provided a promising milieu for cells viability and cells proliferation. From week four onwards, there was a significant reduction in blood urea nitrogen and serum creatinine level in Cell/Gel group, as well as well-organized glomeruli and tubules. Moreover, the expression of pro-inflammatory and profibrotic molecules significantly decreased in the Gel/Cell group, whereas anti-inflammatory gene expression was elevated compared to the Cell group. @*CONCLUSION@#Based on in vivo studies, the renal regenerative ability of the progenitor cells could be further increased by this hydrogel system.

Improvement of IgA Nephropathy and Kidney Regeneration by Functionalized Hyaluronic Acid and Gelatin Hydrogel

BACKGROUND@#Immunoglobulin A (IgA) nephropathy (IgAN) is one of an important cause of progressive kidney disease and occurs when IgA settles in the kidney resulted in disrupts kidney’s ability to filter waste and excess water.Hydrogels are promising material for medical applications owing to their excellent adaptability and filling ability. Herein, we proposed a hyaluronic acid/gelatin (CHO-HA/Gel-NH2 ) bioactive hydrogel as a cell carrier for therapeutic kidney regeneration in IgAN. @*METHODS@#CHO-HA/Gel-NH2 hydrogel was fabricated by Schiff-base reaction without any additional crosslinking agents. The hydrogel concentrations and ratios were evaluated to enhance adequate mechanical properties and biocompatibility for further in vivo study. High serum IgA ddY mice kidneys were treated with human urine-derived renal progenitor cells encapsulated in the hydrogel to investigate the improvement of IgA nephropathy and kidney regeneration. @*RESULTS@#The stiffness of the hydrogel was significantly enhanced and could be modulated by altering the concentrations and ratios of hydrogel. CHO-HA/Gel-NH2 at a ratio of 3/7 provided a promising milieu for cells viability and cells proliferation. From week four onwards, there was a significant reduction in blood urea nitrogen and serum creatinine level in Cell/Gel group, as well as well-organized glomeruli and tubules. Moreover, the expression of pro-inflammatory and profibrotic molecules significantly decreased in the Gel/Cell group, whereas anti-inflammatory gene expression was elevated compared to the Cell group. @*CONCLUSION@#Based on in vivo studies, the renal regenerative ability of the progenitor cells could be further increased by this hydrogel system.

Trends of First-Line Targeted Therapy in Korean Patients With Metastatic Clear Cell Renal Cell Carcinoma: Sunitinib Versus Pazopanib, a Multicenter Study

Purpose@#There have been few reports on comparison between sunitinib and pazopanib as first-line targeted therapy in Korean metastatic clear cell renal cell carcinoma (ccRCC). We sought to analyze the treatment trends of metastatic ccRCC by comparing the effects and adverse events of sunitinib and pazopanib. @*Materials and Methods@#Data of 357 metastatic RCC patients who received the sunitinib or pazopanib as the first-line targeted therapy from the Daegyeong Oncology Study Group database was obtained and analyzed. Among these patients, patients who only clear cell type was confirmed after needle biopsy or nephrectomy were included, and patients who underwent target therapy for less than 3 months were excluded. @*Results@#Of 251 patients who met the inclusion criteria, sunitinib and pazopanib group were identified in 156 (62%) and 95 patients (38%), respectively. Pazopanib group was older (66 years vs. 61 years, p=0.001) and more symptomatic (65% vs. 52%, p=0.037) and had more patients with Karnofsky performance status <80 (20% vs. 11%, p=0.048) and fewer number of organ metastases (p=0.004) compared to sunitinib group. There was no significant difference in disease control rate (88.5% vs. 87.3%, p=0.744), the median progression-free survival (19 months vs. 15 months, p=0.444) and overall survival (25 months vs. 19 months, p=0.721) between sunitinib and pazopanib. The most common grade 3/4 adverse events with sunitinib and pazopanib were anemia (5%) and hand-foot syndrome (3%), respectively. There was no significant difference between sunitinib and pazopanib in number of patients who experienced grade 3/4 adverse events (15% vs. 11%, p=0.275). However, there were more patients who discontinued treatment due to only adverse events in sunitinib group compared to pazopanib group (12% vs. 3%, p=0.020). @*Conclusions@#In Korean metastatic ccRCC, pazopanib tended to be used in patients with poorer health status compared to sunitinib. Sunitinib and pazopanib had no significant difference in treatment effect and survival, but pazopanib had more tolerable adverse events.

IL-10 Deficiency Aggravates Renal Inflammation, Fibrosis and Functional Failure in High-Fat Dieted Obese Mice

BACKGROUND@#High-fat diet-induced obesity is one of the major cause of chronic renal failure. This obesity-related renal failure is mainly caused by inflammatory processes. However, the role of the major anti-inflammatory cytokine interleukin (IL)-10 has not been researched intensively. @*METHODS@#To evaluate the effect of IL-10 deficiency on obesity-related renal failure, the in vivo study was carried with four animal groups; (1) Low-fat dieted C57BL/6 mice, (2) Low-fat dieted IL-10 knockout (KO) mice, (3) High-fat dieted C57BL/6 mice and (4) High-fat dieted IL-10 KO mice group. The analysis was carried with blood/urine chemistry, H&E, Oil-Red-O, periodic acid-Schiff and Masson’s trichrome staining immunohistochemistry and real-time PCR methods. @*RESULTS@#At week 12, high-fat dieted IL-10 KO mice showed 1) severe lipid accumulation in kidneys, cholesterol elevation (in total, serum kidney) and low-density lipoprotein increasion through the SCAP-SREBP2-LDLr pathway; (2) serious histopathologic alterations showing glomerulosclerosis, tubulointerstitial fibrosis and immune cell infiltration; (3) increased pro-inflammatory cytokines and chemokines expression; (4) enhanced renal fibrosis; and (5) serious functional failure with high serum creatinine and BUN and proteinuria excretion compared to other groups. @*CONCLUSION@#IL-10 deficiency aggravates renal inflammation, fibrosis and functional failure in high-fat dieted obese mice, thus IL-10 therapy could be applied to obesity-related chronic renal failure.

IL-10 Deficiency Aggravates Renal Inflammation, Fibrosis and Functional Failure in High-Fat Dieted Obese Mice

BACKGROUND@#High-fat diet-induced obesity is one of the major cause of chronic renal failure. This obesity-related renal failure is mainly caused by inflammatory processes. However, the role of the major anti-inflammatory cytokine interleukin (IL)-10 has not been researched intensively. @*METHODS@#To evaluate the effect of IL-10 deficiency on obesity-related renal failure, the in vivo study was carried with four animal groups; (1) Low-fat dieted C57BL/6 mice, (2) Low-fat dieted IL-10 knockout (KO) mice, (3) High-fat dieted C57BL/6 mice and (4) High-fat dieted IL-10 KO mice group. The analysis was carried with blood/urine chemistry, H&E, Oil-Red-O, periodic acid-Schiff and Masson’s trichrome staining immunohistochemistry and real-time PCR methods. @*RESULTS@#At week 12, high-fat dieted IL-10 KO mice showed 1) severe lipid accumulation in kidneys, cholesterol elevation (in total, serum kidney) and low-density lipoprotein increasion through the SCAP-SREBP2-LDLr pathway; (2) serious histopathologic alterations showing glomerulosclerosis, tubulointerstitial fibrosis and immune cell infiltration; (3) increased pro-inflammatory cytokines and chemokines expression; (4) enhanced renal fibrosis; and (5) serious functional failure with high serum creatinine and BUN and proteinuria excretion compared to other groups. @*CONCLUSION@#IL-10 deficiency aggravates renal inflammation, fibrosis and functional failure in high-fat dieted obese mice, thus IL-10 therapy could be applied to obesity-related chronic renal failure.

Predictive Factors of De Novo Overactive Bladder After Radical Prostatectomy in Patients With Clinically Localized Prostate Cancer: A Prospective Observational Study

Purpose@#To evaluate the incidence of de novo overactive bladder (OAB) and the factors related to its occurrence following radical prostatectomy (RP) in patients with clinically localized prostate cancer (PCa). @*Materials and Methods@#We prospectively examined 50 patients without OAB who underwent RP for clinically localized PCa in our institution from August 2019 to February 2020. We performed assessments using the International Prostate Symptom Score (IPSS), the Overactive Bladder Symptom Score (OABSS), and uroflowmetry before surgery and 3 months after RP. OAB was defined as a score of 1 or more on the urgency components of the OABSS. Three months after RP, the patients were divided into 2 groups based on the presence of de novo OAB symptoms. We evaluated the patients’ demographics and outcomes after RP according to their de novo OAB grouping. The predictive factors of de novo OAB after RP were analyzed using a multivariate logistic regression model. @*Results@#Of the 50 patients, 22 (44%) had de novo OAB 3 months after RP. The patients in the de novo OAB group were older, had higher preoperative IPSS storage subscores, and had larger volumes of postvoid residual urine on preoperative uroflowmetry than those in the non-de novo OAB group. Multivariate analysis showed that age and preoperative IPSS storage subscores were predictive factors of de novo OAB after RP. @*Conclusions@#de novo OAB was observed in 44% of the patients 3 months after RP. Age and preoperative IPSS storage subscores were predictive factors of de novo OAB following RP.

Recurrent Bleeding From Ileal Conduit Stomal Varices in a Patient With Portal Hypertension

Bleeding from ileal conduit stomal varices is a rare complication. The standard treatment for the management of stomal varices has not been established yet. We present the case of a 65-yearold man with recurrent fatal bleeding from his ileal conduit stomal varices who was successfully treated with ligation of the engorged venous varices using hemostatic agents.

Predictive Factors of De Novo Overactive Bladder After Radical Prostatectomy in Patients With Clinically Localized Prostate Cancer: A Prospective Observational Study

Purpose@#To evaluate the incidence of de novo overactive bladder (OAB) and the factors related to its occurrence following radical prostatectomy (RP) in patients with clinically localized prostate cancer (PCa). @*Materials and Methods@#We prospectively examined 50 patients without OAB who underwent RP for clinically localized PCa in our institution from August 2019 to February 2020. We performed assessments using the International Prostate Symptom Score (IPSS), the Overactive Bladder Symptom Score (OABSS), and uroflowmetry before surgery and 3 months after RP. OAB was defined as a score of 1 or more on the urgency components of the OABSS. Three months after RP, the patients were divided into 2 groups based on the presence of de novo OAB symptoms. We evaluated the patients’ demographics and outcomes after RP according to their de novo OAB grouping. The predictive factors of de novo OAB after RP were analyzed using a multivariate logistic regression model. @*Results@#Of the 50 patients, 22 (44%) had de novo OAB 3 months after RP. The patients in the de novo OAB group were older, had higher preoperative IPSS storage subscores, and had larger volumes of postvoid residual urine on preoperative uroflowmetry than those in the non-de novo OAB group. Multivariate analysis showed that age and preoperative IPSS storage subscores were predictive factors of de novo OAB after RP. @*Conclusions@#de novo OAB was observed in 44% of the patients 3 months after RP. Age and preoperative IPSS storage subscores were predictive factors of de novo OAB following RP.

Recurrent Bleeding From Ileal Conduit Stomal Varices in a Patient With Portal Hypertension

Bleeding from ileal conduit stomal varices is a rare complication. The standard treatment for the management of stomal varices has not been established yet. We present the case of a 65-yearold man with recurrent fatal bleeding from his ileal conduit stomal varices who was successfully treated with ligation of the engorged venous varices using hemostatic agents.

Bladder Regeneration Using a Polycaprolactone Scaffold with a Gradient Structure and Growth Factors in a Partially Cystectomized Rat Model

Background@#Tissue engineering can be used for bladder augmentation. However, conventional scaffolds result in fibrosis and graft shrinkage. This study applied an alternative polycaprolactone (PCL)-based scaffold (diameter = 5 mm) with a noble gradient structure and growth factors (GFs) (epidermal growth factor, vascular endothelial growth factor, and basic fibroblast growth factor) to enhance bladder tissue regeneration in a rat model. @*Methods@#Partially excised urinary bladders of 5-week-old male Slc:SD rats were reconstructed with the scaffold (scaffold group) or the scaffold combined with GFs (GF group) and compared with sham-operated (control group) and untreated rats (partial cystectomy group). Evaluations of bladder volume, histology, immunohistochemistry (IHC), and molecular markers were performed at 4, 8, and 12 weeks after operation. @*Results@#The bladder volumes of the scaffold and GF group recovered to the normal range, and those of the GF group showed more enhanced augmentation. Histological evaluations revealed that the GF group showed more organized urothelial lining, dense extracellular matrix, frequent angiogenesis, and enhanced smooth muscle bundle regeneration than the scaffold group. IHC for α-smooth muscle actin, pan-cytokeratin, α-bungarotoxin, and CD8 revealed that the GF group showed high formation of smooth muscle, blood vessel, urothelium, neuromuscular junction and low immunogenicity. Concordantly, real-time polymerase chain reaction experiments revealed that the GF group showed a higher expression of transcripts associated with smooth muscle and urothelial differentiation. In a 6-month in vivo safety analysis, the GF group showed normal histology. @*Conclusion@#This study showed that a PCL scaffold with a gradient structure incorporating GFs improved bladder regeneration functionally and histologically.

Serum Testosterone Level Can Be Predictive Factor for Upstaging in Clinically Localized Prostate Cancer

Purpose@#To determine an appropriate surgical technique, it is important to predict pathological results for patientswith clinically localized prostate cancer (PCa) eligible for nerve-sparing radical prostatectomy (NSRP). Severalstudies have highlighted that serum testosterone level was associated with aggressive features of PCa. Therefore,we analyzed factors, including serum testosterone, to predict upstaging and upgrading after surgery for patientswith clinically localized PCa eligible for NSRP. @*Materials and Methods@#We retrospectively evaluated patients who underwent radical prostatectomy (RP) betweenJanuary 2015 and May 2018 at our institution. Patients with Gleason grade group 1 or 2 on biopsy,prostate-specific antigen<10, and ≤clinical/radiologic stage T2 were included in this study. Upstaging andupgrading were defined as pathological stage≥T3a and Gleason grade group≥3, respectively. We evaluatedthe patients’ demographics and outcomes according to upstaging and upgrading after surgery. Predictive factorsfor upstaging and upgrading were analyzed using a multivariate logistic regression model. @*Results@#Of 108 patients included in the study, upstaging and upgrading after surgery were observed in 24 (22.2%)and 36 (33.3%), respectively. Low serum testosterone level, small prostate size, and positive core number≥3on biopsy were identified as predictive factors for upstaging in multivariate analysis. Although serum testosteronewas associated with upgrading in univariate analysis, only clinical/radiologic stage and biopsy Gleason grade groupwere observed as predictive factors for upgrading in multivariate analysis. @*Conclusions@#Serum testosterone level was identified as a predictive factor for upstaging after RP for clinicallylocalized PCa eligible for NSRP.

Impact of Multiple Prostate Biopsies: Risk of Perioperative Complications and Biochemical Recurrence After Radical Prostatectomy

Purpose@#The aim of this study was to analyze the perioperative complications and oncological outcomes of radical prostatectomy (RP) in patients who underwent multiple prostate biopsies. @*Materials and Methods@#A total of 1,112 patients who underwent RP between January 2009 and April 2016 at 4 different centers were included in this study. We divided these patients into 2 groups: patients who underwent only 1st biopsy, and those who underwent 2nd or more repeated biopsies. The association between the number of prior biopsies and perioperative complications and biochemical recurrence (BCR) was analyzed. @*Results@#Of 1,112 patients, 1,046 patients (94.1%) underwent only 1st biopsy, and 66 (5.9%) underwent 2nd or more repeated biopsies. There were no significant differences in preoperative prostate-specific antigen levels, operation times, blood loss volumes, or hospital stay durations (all p＞0.05). Patients who underwent multiple prostate biopsies presented with a localized tumor significantly more often (p＜0.05). The Gleason score and rate of positive surgical margins were significantly lower in patients with multiple biopsies (all p＜0.05). The Cox proportional hazards model analysis indicated that there was no association between the number of prior prostate biopsies and BCR (p＞0.05). Kaplan-Meier curve analysis indicated that BCR-free survival rates between the 2 groups were similar (p＞0.05). @*Conclusions@#Multiple prostate biopsies are not associated with an increased risk of perioperative complications, adverse pathological outcomes, or higher rates of BCR in patients who have undergone RP. (Korean J Urol Oncol 2020;18:24-31)

Efficacy of Androgen Deprivation Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer Receiving Docetaxel-Based Chemotherapy

PURPOSE: The purpose of this study was to determine the comparative effectiveness of androgen deprivation therapy (ADT) combined with docetaxel (DTX)-based chemotherapy in Korean and Japanese castration-resistant prostate cancer (CRPC) patient cohorts.MATERIALS AND METHODS: Metastatic CRPC patients who underwent more than three DTX-based chemotherapy cycles in Korea and Japan between 2002 and 2017 were retrospectively analyzed and divided into the DTX-only (DTX, n=30) and combination (DTX+ADT, n=46) groups. Progression-free survival (PFS) was calculated as the time from the start of chemotherapy to the occurrence of either disease progression (prostate-specific antigen [PSA] progression or radiographic progression) or death. The primary end point was PFS and the secondary end point was overall survival (OS).RESULTS: In the DTX and DTX+ADT groups, the median PFS was 6.0 and 11.0 months (log-rank p=0.053). The multivariate Cox regression analysis revealed that the significant predicting factors of PFS were ADT administration (hazard ratio [HR], 0.478; 95% confidence interval [CI], 0.284–0.804; p=0.005) and number of DTX-based chemotherapy cycles (HR, 0.934; 95% CI, 0.899–0.970; p<0.001). In the DTX and DTX+ADT groups, the median OS was 16.0 and 19.5 months (log-rank p=0.825). Through multiple Cox regression analysis, we found that the significant predicting factors of OS were the PSA nadir level (HR, 1.001; 95% CI, 1.000–1.002; p<0.001) and number of DTX-based chemotherapy cycles (HR, 0.932; 95% CI, 0.876–0.991; p=0.024).CONCLUSIONS: Concurrent DTX-based chemotherapy and ADT may be beneficial compared with DTX-based chemotherapy alone in chemotherapy-naïve metastatic CRPC patients in terms of the PFS, but not the OS.

In Vivo Safety and Regeneration of Long-Term Transported Amniotic Fluid Stem Cells for Renal Regeneration

BACKGROUND: Despite major progress in stem cell therapy, our knowledge of the characteristics and tissue regeneration potency of long-term transported cells is insufficient. In a previous in vitro study, we established the optimal cell transport conditions for amniotic fluid stem cells (AFSCs). In the present study, the target tissue regeneration of long-term transported cells was validated in vivo. METHODS: For renal regeneration, transported AFSCs were seeded on a poly(lactide-co-glycolide) scaffold and implanted in a partially resected kidney. The target tissue regeneration of the transported cells was compared with that of freshly harvested cells in terms of morphological reconstruction, histological microstructure reformation, immune cell infiltration, presence of induced cells, migration into remote organs, expression of inflammation/fibrosis/renal differentiation-related factors, and functional recovery. RESULTS: The kidney implanted with transported cells showed recovery of total kidney volume, regeneration of glomerular/renal tubules, low CD4/CD8 infiltration, and no occurrence of cancer during 40 weeks of observation. The AFSCs gradually disappeared and did not migrate into the liver, lung, or spleen. We observed low expression levels of proinflammatory cytokines and fibrotic factors; enhanced expression of the genes Wnt4, Pax2, Wt1, and Emx2; and significantly reduced blood urea nitrogen and creatinine values. There were no statistical differences between the performance of freshly harvested cells and that of the transported cells. CONCLUSION: This study demonstrates that long-term transported cells under optimized conditions can be used for cell therapy without adverse effects on stem cell characteristics, in vivo safety, and tissue regeneration potency.

Susceptibility of the Index Urinary Tract Infection to Prophylactic Antibiotics Is a Predictive Factor of Breakthrough Urinary Tract Infection in Children with Primary Vesicoureteral Reflux Receiving Continuous Antibiotic Prophylaxis

BACKGROUND: Few studies have reported on breakthrough urinary tract infection (UTI) associated with the susceptibility of index UTI to prophylactic antibiotics in children with primary vesicoureteral reflux (VUR) receiving continuous antibiotic prophylaxis (CAP). We assessed the impact of the susceptibility of index UTI to prophylactic antibiotics in breakthrough UTIs in children with primary VUR receiving CAP. METHODS: We retrospectively reviewed the medical records of 81 children with primary VUR who were diagnosed after febrile or symptomatic UTI and subsequently received trimethoprim-sulfamethoxazole (TMP-SMX) as CAP between January 2010 and December 2013. We allocated children to a susceptible group or a resistant group based on the susceptibility of index UTI to TMP-SMX. We evaluated patient demographics and clinical outcomes after CAP according to the susceptibility of index UTI to TMP-SMX. Multivariate analysis was used to identify the predictive factors for breakthrough UTI. RESULTS: Of the 81 children, 42 were classified into the susceptible group and 39 into the resistant group. The proportion of breakthrough UTI was 31.0% (13/42) in the susceptible group and 53.8% (21/39) in the resistant group (P = 0.037). Progression of renal scarring was observed in 0% of children in the susceptible group and 15% in the resistant group (P = 0.053). Multivariate analysis showed that TMP-SMX resistance and initial renal scarring were significant predictors of breakthrough UTI. CONCLUSION: Susceptibility of index UTI to prophylactic antibiotics is a risk factor of breakthrough UTI and is associated with poor clinical outcomes in children with primary VUR receiving CAP.

Preparation and Characterization of Human Adipose Tissue-Derived Extracellular Matrix, Growth Factors, and Stem Cells: A Concise Review

BACKGROUND: Human adipose tissue is routinely discarded as medical waste. However, this tissue may have valuable clinical applications since methods have been devised to effectively isolate adipose-derived extracellular matrix (ECM), growth factors (GFs), and stem cells. In this review, we analyze the literature that devised these methods and then suggest an optimal method based on their characterization results. METHODS: Methods that we analyze in this article include: extraction of adipose tissue, decellularization, confirmation of decellularization, identification of residual active ingredients (ECM, GFs, and cells), removal of immunogens, and comparing structural/physiological/biochemical characteristics of active ingredients. RESULTS: Human adipose ECMs are composed of collagen type I–VII, laminin, fibronectin, elastin, and glycosaminoglycan (GAG). GFs immobilized in GAG include basic fibroblast growth factor (bFGF), transforming growth factor beta 1(TGF-b1), insulin like growth factor 1 (IGF-1), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), BMP4 (bone morphogenetic protein 4), nerve growth factor (NGF), hepatocyte growth factor (HGF), and epithermal growth factor (EGF). Stem cells in the stromal-vascular fraction display mesenchymal markers, self-renewal gene expression, and multi-differentiation potential. CONCLUSION: Depending on the preparation method, the volume, biological activity, and physical properties of ECM, GFs, and adipose tissue-derived cells can vary. Thus, the optimal preparation method is dependent on the intended application of the adipose tissue-derived products.

Oncological and functional outcomes following robot-assisted laparoscopic radical prostatectomy at a single institution: a minimum 5-year follow-up / 영남의대학술지

BACKGROUND@#To evaluate mid-term oncological and functional outcomes in patients with prostate cancer treated by robot-assisted laparoscopic radical prostatectomy (RALP) at our institution.@*METHODS@#We retrospectively reviewed the medical records of 128 patients with prostate cancer who underwent RALP at our institution between February 2008 and April 2010. All patients enrolled in this study were followed up for at least 5 years. We analyzed biochemical recurrence (BCR)-free survival using a Kaplan-Meier survival curve analysis and predictive factors for BCR using multivariate Cox regression analysis. Continence recovery rate, defined as no use of urinary pads, was also evaluated.@*RESULTS@#Based on the D'Amico risk classification, there were 30 low-risk patients (23.4%), 47 intermediate-risk patients (38.8%), and 51 high-risk patients (39.8%), preoperatively. Based on pathological findings, 50.0% of patients (64/128) showed non-organ confined disease (≥T3a) and 26.6% (34/128) had high grade disease (Gleason score ≥8). During a median follow-up period of 71 months (range, 66–78 months), the frequency of BCR was 33.6% (43/128) and the median BCR-free survival was 65.9 (0.4–88.0) months. Multivariate Cox regression analysis revealed that high grade disease (Gleason score ≥8) was an independent predictor for BCR (hazard ratio=4.180, 95% confidence interval=1.02–17.12, p=0.047). In addition, a majority of patients remained continent following the RALP procedure, without the need for additional intervention for post-prostatectomy incontinence.@*CONCLUSION@#Our study demonstrated acceptable outcomes following an initial RALP procedure, despite 50% of the patients investigated demonstrating high-risk features associated with non-organ confined disease.

Partial versus Radical Nephrectomy for T1-T2 Renal Cell Carcinoma in Patients with Chronic Kidney Disease Stage III: a Multiinstitutional Analysis of Kidney Function and Survival Rate

BACKGROUND: To examine survival rates and renal function after partial nephrectomy (PN) and radical nephrectomy (RN) in patients with chronic kidney disease (CKD). METHODS: We studied 4,332 patients who underwent PN or RN for pathological T1a-T2N0M0 renal cell carcinoma from 1988 to 2014. Patients were divided into two subgroups of CKD stage I–II and stage III. Kidney function, and survival outcomes were compared between groups. RESULTS: We included 1,756 patients with CKD I–II and 276 patients with CKD III in the final pair-matched analysis. Kidney function was significantly better preserved in the PN than in the RN group among all patients. However, the beneficial effect of PN on kidney function gradually disappeared over time in CKD III patients. The 5-year overall survival (OS) rates after PN and RN differed in patients with CKD I–II disease (99.4% vs. 96.5%, respectively, P = 0.015). The 5-year OS rates after surgery were not affected by mode of nephrectomy in CKD III patients (97.8% vs. 93.5%, P = 0.103). The 5-year cancer-specific survival rates did not differ between treatment groups in all CKD stage. Cox hazard analysis showed that the operative method was a significant factor for OS in CKD I–II patients (hazard ratio [HR], 0.320; confidence interval [CI], 0.122–0.840; P = 0.021). However, PN was not beneficial in terms of OS in CKD III patients (HR, 0.395; CI, 0.086–1.172; P = 0.117). CONCLUSION: PN is associated with a higher OS rate and better kidney function in patients with preoperative CKD stage I and II, but not in those with CKD stage III.