Anti-Metastatic Effect of Pyruvate Dehydrogenase Kinase 4 Inhibition in Bladder Cancer via the ERK, SRC, and JNK Pathways.

Bladder cancer is a common global cancer with a high percentage of metastases and high mortality rate. Thus, it is necessary to identify new biomarkers that can be helpful in diagnosis. Pyruvate dehydrogenase kinase 4 (PDK4) belongs to the PDK family and plays an important role in glucose utilization in living organisms. In the present study, we evaluated the role of PDK4 in bladder cancer and its related protein changes. First, we observed elevated PDK4 expression in high-grade bladder cancers. To screen for changes in PDK4-related proteins in bladder cancer, we performed a comparative proteomic analysis using PDK4 knockdown cells. In bladder cancer cell lines, PDK4 silencing resulted in a lower rate of cell migration and invasion. In addition, a PDK4 knockdown xenograft model showed reduced bladder cancer growth in nude mice. Based on our results, PDK4 plays a critical role in the metastasis and growth of bladder cancer cells through changes in ERK, SRC, and JNK.

Targeted therapy response in early versus late recurrence of renal cell carcinoma after surgical treatment: A propensity score-matched study using the Korean Renal Cancer Study Group database.

OBJECTIVES: To investigate the clinicopathological features and outcomes of targeted therapy in patients with recurrence of renal cell carcinoma in <5 years or ≥5 years after the surgical treatment for renal cell carcinoma. METHODS: Patients with metastatic renal cell carcinoma treated with targeted therapy in a multicenter database were retrospectively characterized according to time from surgery to recurrence. Early recurrence was defined as recurrence within 5 years after surgery, and late recurrence was defined as occurring ≥5 years after surgery. The propensity scores for recurrence status were calculated, and patients with late recurrence were matched to patients with early recurrence at a 1:3 ratio. The oncological outcomes of targeted therapy in both groups were compared. RESULTS: Among 716 patients, 512 (71.5%) experienced early recurrence and 204 (28.5%) experienced late recurrence. The patients with late recurrence presented with younger age at surgery, lower tumor stages and Fuhrman grade, and fewer sarcomatoid features and lymphovascular invasion (all P < 0.005). All differences in clinicopathological characteristics before targeted therapy disappeared after matching. Patients with late recurrence had significantly longer median overall survival (56 months vs 36 months; P < 0.0001) and median first-line progression-free survival (12 months vs 8 months; P = 0.031). The early recurrence status was a significantly worse predictor for overall survival and first-line progression-free survival (hazard ratio 1.30, P = 0.007; and hazard ratio 1.76, P < 0.001, respectively). CONCLUSIONS: Late recurrence might have prognostic value in terms of oncological outcomes in metastatic renal cell carcinoma treated with targeted therapy.

Clinical factors that influence the occurrence of symptomatic pseudoaneurysms and arteriovenous fistulas after partial nephrectomy: multi-institutional study of renal function outcomes after one year of selective arterial embolization.

PURPOSE: Renal artery pseudoaneurysms (RAPs) and arteriovenous fistulas (AVFs) are rare but potentially life-threatening complications after partial nephrectomy (PN). Selective arterial embolization (SAE) is an effective method for controlling RAPs/AVFs. We assessed the clinical factors affecting the occurrence of RAPs/AVFs after PN and the effects of SAE on postsurgical renal function. MATERIALS AND METHODS: Four hundred ninety-three patients who underwent PN were retrospectively reviewed. They were placed in either the SAE or the non-SAE group. The effects of clinical factors, including R.E.N.A.L. scores, on the occurrence of RAPs/AVFs were analyzed. The influence of SAE on the estimated glomerular filtration rate (eGFR) during the first postoperative year was evaluated. RESULTS: Thirty-three (6.7%) patients experienced RAPs/AVFs within 8 days of the median interval between PN and SAE. The SAE group had significantly higher R.E.N.A.L. scores, higher N component scores, and higher L component scores (all, p <0.05). In the multivariate analysis, higher N component scores were associated with the occurrence of RAPs/AVFs (Odds ratio: 1.96, p=0.039). In the SAE group, the mean 3-day postembolization eGFR was significantly lower than the mean 3-day postoperative eGFR (p <0.01). This difference in the eGFRs was still present 1 year later. CONCLUSIONS: Renal tumors located near the renal sinus and collecting system were associated with a higher risk for RAPs/AVFs after PN. Although SAE was an effective method for controlling symptomatic RAPs/AVFs after PN, a procedure-related impairment of renal function after SAE could occur and still be present at the end of the first postoperative year.

Association between De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) and oncological outcomes in bladder cancer patients after radical cystectomy.

BACKGROUND: New biological prognostic predictors have been studied; however, some factors have limited clinical application due to tissue-specific expression and high cost. There is the need for a promising predictive factor that is simple to detect and that is closely linked to oncological outcomes in patients with urothelial bladder cancer (BC) who have undergone radical cystectomy (RC). Therefore, we investigated the clinical prognostic value of the preoperative De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) on oncological outcomes in patients with urothelial BC after RC. METHODS: We retrospectively evaluated clinicopathological data of 118 patients with non-metastatic urothelial BC after RC between 2008 and 2013 at a single center. The association between the De Ritis ratio and clinicopathological findings was assessed. The potential prognostic value of the De Ritis ratio was analyzed using the Kaplan-Meier method, and multivariate Cox analyses were performed to identify the independent predictors of metastasis-free survival, cancer-specific survival, and overall survival. RESULTS: According to the receiver operating curve of the De Ritis ratio for metastasis, we stratified the patients into 2 groups using a threshold of 1.3. A high De Ritis ratio was more likely to be associated with old age and the female sex. Kaplan-Meier estimates revealed that patients with a high De Ritis ratio had inferior metastasis-free survival, cancer-specific survival, and overall survival outcomes (P = 0.012, 0.024, and 0.022, respectively). Multivariate analysis revealed that a high De Ritis ratio was an independent prognostic factor for metastasis (hazard ratio [HR], 2.389; 95% confidence interval [CI], 1.161-4.914; P = 0.018), cancer-related death (HR, 2.755; 95% CI, 1.214-6.249; P = 0.015), and overall death (HR, 2.761; 95% CI, 1.257-6.067; P = 0.011). CONCLUSIONS: An elevated De Ritis ratio was significantly associated with worse prognosis in patients who underwent RC for urothelial BC. This ratio might further improve the predictive accuracy for prognosis in BC.

Predictive factors for adrenal metastasis in extra-adrenal malignancy patients with solitary adrenal mass.

BACKGROUND AND OBJECTIVES: The adrenal gland is a frequent site for metastasis, and a solitary adrenal mass is often observed during staging workup or imaging follow-up in patients with extra-adrenal malignancy. To create an appropriate management plan, it is essential to distinguish between benign adrenal lesions and metastasis in patients with extra-adrenal cancer having solitary adrenal masses. Therefore, here we evaluated the predictive factors for adrenal metastasis in patients with extra-adrenal malignancy having solitary adrenal mass. MATERIALS AND METHODS: From September 2003 to June 2016, we retrospectively reviewed patients with extra-adrenal malignancy having solitary adrenal mass on a cancer staging workup or follow-up study who subsequently underwent adrenalectomy at our institution. All patients underwent preoperative functional studies; those with positive results were excluded from this study. Characteristics of oncology patients with adrenal mass including age, sex, body mass index, smoking, mass location, mass size, hypertension, diabetes mellitus, precontrast Hounsfield unit (HU), and synchronous or metachronous adrenal mass based on the time of the extra-adrenal cancer diagnosis were analyzed. RESULTS: Of the total 68 patients with extra-adrenal cancer having solitary adrenal mass, 22 had pathologically confirmed adrenal metastasis. Primary cancers consisted of hepatocellular cell carcinoma (n = 7), renal cell carcinoma (n = 7), lung cancer (n = 4), colon cancer (n = 3), and breast cancer (n = 1). On multivariate analysis, a higher precontrast HU (P = 0.001, odds ratio [OR] = 1.105, 95% confidence interval [CI] = 1.042-1.172), male sex ( P = 0.019, OR = 9.782, 95% CI = 1.462-65.461), and metachronous adrenal mass ( P = 0.007, OR = 11.090, 95% CI = 1.937-63.490) were observed as predictive factors for adrenal metastasis in patients with extra-adrenal cancer having solitary adrenal mass. The cut-off value of precontrast HU to distinguish between metastasis and benign lesions was 36.2 (sensitivity = 81.8%; specificity = 91.3%). CONCLUSION: High precontrast HU (> 36), male sex, and metachronous adrenal mass are predictive factors for adrenal metastasis in patients with extra-adrenal malignancy having solitary adrenal mass.

Activated carbon fiber filters could reduce the risk of surgical smoke exposure during laparoscopic surgery: application of volatile organic compounds.

BACKGROUND: Generation of smoke is inevitable during surgical procedures. Some volatile organic compounds (VOCs) in surgical smoke are known to be strong carcinogens. We used a prototype of a multi-layered complex filter in an attempt to eliminate VOCs. METHODS: From June 2015 to July 2015, 20 patients underwent transperitoneal laparoscopic nephrectomy for renal cell carcinoma. Smoke (pre-filter) was collected 20 min after the electrocautery device was first used during the surgery, by the direct collection method, with a 5-L Tedlar® gas-sampling bag. Twenty and 120 min after the filter was applied, smoke (post-filter) was again collected using the same method. The sample was analyzed by gas chromatography and mass spectrography. The cancer risk and hazard quotient were analyzed based on US Environmental Protection Agency guidelines. RESULTS: Twenty patients with a median age of 54.5 (30-80) years were enrolled in the study. Eighteen VOCs were detected using the Japanese indoor air standards mix analysis. The total elimination rate of the VOCs was 86.49 ± 2.83%. The post-filter (120 min) cancer risk (mean ± standard deviation) reduced to a negligible level for benzene, ethylbenzene, and styrene except 1,2-dichloroethane. The post-filter (120 min) hazard quotient for each compound decreased to levels posing a negligible risk for acetone, hexane, benzene, toluene, p-xylene, o-xylene, and styrene. CONCLUSION: Strong carcinogens, such as 1,2-dichloroethane, benzene, and ethylbenzene, were eliminated by more than 85% by using this activated carbon fiber filter and the risks from these compounds decreased to an almost negligible level. We suggest using every measure, including these filters, to protect the health of operating room personnel.

Open radical prostatectomy reproducing robot-assisted radical prostatectomy: Involving antegrade nerve sparing and continuous anastomosis.

PURPOSE: To present modified RRP using the same method as RALP and compare its surgical outcomes with RALP. MATERIALS AND METHODS: Demographics, perioperative and functional outcomes of the 322 patients that underwent RRP (N=99) or RALP (N=223) at our institution from January 2011 through June 2013 were evaluated retrospectively. Postoperative incontinence and erectile dysfunction are involved functional outcomes. During the modified procedure, the bladder neck was dissected first as for RALP. After dissection of vas deference and seminal vesicle, the prostate was dissected in an antegrade fashion with bilateral nerve saving. Finally, the urethra was cut at the prostate apex. After a Rocco suture was applied, and then urethrovesical anastomosis was performed with continuous suture as for RALP. RESULTS: Perioperative characteristics and complication rates were similar in the RRP and RALP groups except for mean estimated blood loss (p<0.001) and operative time (p<0.001). Incontinence rates at 3 and 12 months after RRP decreased from 67.6% to 10.1 and after RALP decreased from 53.4% to 5.4%. Positive surgical margin rates were non-significantly different in the RRP and RALP groups (30.3% and 37.2%, respectively). Overall postoperative potency rate at 12 months was not significant different in RRP and RALP groups (34.3% and 43.0%). CONCLUSIONS: RRP reproducing RALP was found to have surgical outcomes comparable to RALP. This technique might be adopted by experienced urologic surgeons as a standard procedure.

Advanced Properties of Urine Derived Stem Cells Compared to Adipose Tissue Derived Stem Cells in Terms of Cell Proliferation, Immune Modulation and Multi Differentiation.

Adipose tissue stem cells (ADSCs) would be an attractive autologous cell source. However, ADSCs require invasive procedures, and has potential complications. Recently, urine stem cells (USCs) have been proposed as an alternative stem cell source. In this study, we compared USCs and ADSCs collected from the same patients on stem cell characteristics and capacity to differentiate into various cell lineages to provide a useful guideline for selecting the appropriate type of cell source for use in clinical application. The urine samples were collected via urethral catheterization, and adipose tissue was obtained from subcutaneous fat tissue during elective laparoscopic kidney surgery from the same patient (n = 10). Both cells were plated for primary culture. Cell proliferation, colony formation, cell surface markers, immune modulation, chromosome stability and multi-lineage differentiation were analyzed for each USCs and ADSCs at cell passage 3, 5, and 7. USCs showed high cell proliferation rate, enhanced colony forming ability, strong positive for stem cell markers expression, high efficiency for inhibition of immune cell activation compared to ADSCs at cell passage 3, 5, and 7. In chromosome stability analysis, both cells showed normal karyotype through all passages. In analysis of multi-lineage capability, USCs showed higher myogenic, neurogenic, and endogenic differentiation rate, and lower osteogenic, adipogenic, and chondrogenic differentiation rate compared to ADSCs. Therefore, we expect that USC can be an alternative autologous stem cell source for muscle, neuron and endothelial tissue reconstruction instead of ADSCs.

Human Urine-derived Stem Cells Seeded Surface Modified Composite Scaffold Grafts for Bladder Reconstruction in a Rat Model.

We conducted this study to investigate the synergistic effect of human urine-derived stem cells (USCs) and surface modified composite scaffold for bladder reconstruction in a rat model. The composite scaffold (Polycaprolactone/Pluronic F127/3 wt% bladder submucosa matrix) was fabricated using an immersion precipitation method, and heparin was immobilized on the surface via covalent conjugation. Basic fibroblast growth factor (bFGF) was loaded onto the heparin-immobilized scaffold by a simple dipping method. In maximal bladder capacity and compliance analysis at 8 weeks post operation, the USCs-scaffold(heparin-bFGF) group showed significant functional improvement (2.34 ± 0.25 mL and 55.09 ± 11.81 µL/cm H2O) compared to the other groups (2.60 ± 0.23 mL and 56.14 ± 9.00 µL/cm H2O for the control group, 1.46 ± 0.18 mL and 34.27 ± 4.42 µL/cm H2O for the partial cystectomy group, 1.76 ± 0.22 mL and 35.62 ± 6.69 µL/cm H2O for the scaffold group, and 1.92 ± 0.29 mL and 40.74 ± 7.88 µL/cm H2O for the scaffold(heparin-bFGF) group, respectively). In histological and immunohistochemical analysis, the USC-scaffold(heparin-bFGF) group showed pronounced, well-differentiated, and organized smooth muscle bundle formation, a multi-layered and pan-cytokeratin-positive urothelium, and high condensation of submucosal area. The USCs seeded scaffold(heparin-bFGF) exhibits significantly increased bladder capacity, compliance, regeneration of smooth muscle tissue, multi-layered urothelium, and condensed submucosa layers at the in vivo study.

Surgical smoke may be a biohazard to surgeons performing laparoscopic surgery.

BACKGROUND: Surgical smoke production is inevitable during surgical procedures. Although many workplaces have adopted smoke-free environments, healthcare workers, especially surgeons, continue to be exposed to surgical smoke. METHODS: From February 2013 to March 2013, a total of 20 patients underwent transperitoneal laparoscopic nephrectomy for renal cell carcinoma. A 5-L gas sample was collected 30 min after the electrocautery device was first used and was analyzed by gas chromatography and mass spectrometry. Cancer risk was calculated for carcinogenic compounds and hazard quotient was calculated for noncarcinogenic compounds using US Environmental Protection Agency guidelines. RESULTS: Twenty patients with a median age of 57.5 years were enrolled in the study. Eighteen volatile organic compounds were detected by Japanese indoor air standards mix analysis. The cancer risks were ethanol, 5.10 × 10(-5) ± 6.35 × 10(-5); 1,2-dichloroethane, 4.75 × 10(-3) ± 7.42 × 10(-4); benzene, 1.09 × 10(-3) ± 4.33 × 10(-4); ethylbenzene, 2.87 × 10(-5) ± 1.32 × 10(-5); and styrene, 2.94 × 10(-6) ± 1.16 × 10(-6). The hazard quotients were acetone, 1.88 × 10(-2) ± 7.63 × 10(-3); hexane, 1.48 × 10(-1) ± 8.70 × 10(-2); benzene, 4.66 ± 1.85; toluene, 2.61 × 10(-2) ± 7.23 × 10(-3); p-xylene, 1.81 × 10(-1) ± 6.45 × 10(-2); o-xylene, 2.40 × 10(-2) ± 3.33 × 10(-2); and styrene, 5.15 × 10(-3) ± 2.03 × 10(-3). CONCLUSIONS: For five carcinogenic compounds detected, the cancer risk was greater than negligible. For 1,2-dichloroethane and benzene, the risk was classified as unacceptable. Analysis of noncarcinogenic compounds showed that risk reduction measures are needed for benzene. Even though surgical smoke is not an immediate health hazard, operating room personnel should be aware of the potential long-term health risks associated with exposure.

Decreased selenium-binding protein 1 mRNA expression is associated with poor prognosis in renal cell carcinoma.

BACKGROUND: The anticancer effects of selenium may be mediated by selenium-binding proteins, such as SELENBP1. The association between SELENBP1 expression levels and clinicopathologic parameters was assessed in renal cell carcinoma (RCC). METHODS: SELENBP1 mRNA expression was measured with real-time quantitative polymerase chain reaction (qPCR) in 139 specimens of primary RCC and 59 specimens of donor-matched normal-appearing kidney tissues. The prognostic effect of SELENBP1 levels was evaluated with Kaplan-Meier and multivariate Cox regression analyses. RESULTS: SELENBP1 mRNA levels were significantly lower in tumor tissues than in matched normal kidney tissues (P < 0.001) and significantly inversely correlated with pathologic (T-stage and Fuhrman grade) and prognostic variables (progression and cancer-specific death). Kaplan-Meier estimates showed that low SELENBP1 expression was significantly correlated with cancer-specific death (log-rank test, P = 0.014), and a multivariate Cox regression model revealed that SELENBP1 expression was an independent predictor of cancer-specific death (HR, 0.111; P = 0.006). CONCLUSIONS: SELENBP1 might play a role in tumor suppression and could be a useful prognostic factor in RCC.

Progression-directed therapy in patients with oligoprogressive castration-resistant prostate cancer.

PURPOSE: Oligoprogressive lesions are observed in a subset of patients who progress to castration-resistant prostate cancer (CRPC), while other lesions remain controlled by systemic therapy. This study evaluates the impact of progression-directed therapy (PDT) on these oligoprogressive lesions. MATERIALS AND METHODS: This retrospective study included 40 patients diagnosed with oligoprogressive CRPC. PDT was performed for treating all progressive sites using radiotherapy. Fifteen patients received PDT using radiotherapy for all progressive sites (PDT group) while 25 had additional first-line systemic treatments (non-PDT group). In PDT group, 7 patients underwent PDT and unchanged systemic therapy (PDT-A group) and 8 patients underwent PDT with additional new line of systemic therapy on CRPC (PDT-B group). The Kaplan-Meier method was used to assess treatment outcomes. RESULTS: The prostate specific antigen (PSA) nadir was significantly lower in PDT group compare to non-PDT group (p=0.007). A 50% PSA decline and complete PSA decline were observed in 13 patients (86.7%) and 10 patients (66.7%) of PDT group and in 18 patients (72.0%) and 11 patients (44.0%) of non-PDT group, respectively. The PSA-progression free survival of PDT-B group was significantly longer than non-PDT group. The median time to failure of first-line systemic therapy on CRPC was 30.2 months in patients in PDT group and 14.9 months in non-PDT group (p=0.014). PDT-B group showed a significantly longer time to progression than non-PDT group (p=0.025). Minimal PDT-related adverse events were observed. CONCLUSIONS: PDT can delay progression of disease and enhance treatment efficacy with acceptable tolerability in oligoprogressive CRPC.

High-Speed Clearing and High-Resolution Staining for Analysis of Various Markers for Neurons and Vessels.

BACKGROUND: Tissue clearing enables deep imaging in various tissues by increasing the transparency of tissues, but there were limitations of immunostaining of the large-volume tissues such as the whole brain. METHODS: Here, we cleared and immune-stained whole mouse brain tissues using a novel clearing technique termed high-speed clearing and high-resolution staining (HCHS). We observed neural structures within the cleared brains using both a confocal microscope and a light-sheet fluorescence microscope (LSFM). The reconstructed 3D images were analyzed using a computational reconstruction algorithm. RESULTS: Various neural structures were well observed in three-dimensional (3D) images of the cleared brains from Gad-green fluorescent protein (GFP) mice and Thy 1-yellow fluorescent protein (YFP) mice. The intrinsic fluorescence signals of both transgenic mice were preserved after HCHS. In addition, large-scale 3D imaging of brains, immune-stained by the HCHS method using a mild detergent-based solution, allowed for the global topological analysis of several neuronal markers such as c-Fos, neuronal nuclear protein (NeuN), Microtubule-associated protein 2 (Map2), Tuj1, glial fibrillary acidic protein (GFAP), and tyrosine hydroxylase (TH) in various anatomical regions in the whole mouse brain tissues. Finally, through comparisons with various existing tissue clearing methodologies such as CUBIC, Visikol, and 3DISCO, it was confirmed that the HCHS methodology results in relatively less tissue deformation and higher fluorescence retention. CONCLUSION: In conclusion, the development of 3D imaging based on novel tissue-clearing techniques (HCHS) will enable detailed spatial analysis of neural and vascular networks present within the brain.

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.

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.

Grave-to-cradle: human embryonic lineage tracing from the postmortem body.

Curiosity concerning the process of human creation has been around for a long time. Relevant questions seemed to be resolved with the knowledge of how cells divide after fertilization obtained through in vitro fertilization experiments. However, we still do not know how human life is created at the cellular level. Recently, the value of cadavers as a resource from which to obtain "normal" cells and tissues has been established, and human research using postmortem bodies has attracted growing scientific attention. As the human genome can be analyzed at the level of nucleotides through whole-genome sequencing, individual cells in a postmortem body can be traced back to determine what developmental processes have transpired from fertilization. These retrospective lineage tracing studies have answered several unsolved questions on how humans are created. This review covers the methodologies utilized in lineage tracing research in a historical context and the conceptual basis for reconstructing the division history of cells in a retrospective manner using postzygotic somatic variants in postmortem tissue. We further highlight answers that postmortem research could potentially address and discuss issues that wait to be solved in the future.

Clinical characteristics of surgically managed patients with asymptomatic renal stones: Comparison of patients with symptomatic renal stones.

PURPOSE: This study aimed to compare the characteristics of asymptomatic and symptomatic nephrolithiasis in patients who underwent surgical treatment for kidney stones. MATERIALS AND METHODS: Between 2015 and 2019, 245 patients who underwent percutaneous nephrolithotomy or retrograde intrarenal surgery for kidney stones were included. The patients were divided into asymptomatic (n=124) and symptomatic (n=121) groups. All patients underwent blood and urine tests, preoperative non-contrast computed tomography, and postoperative stone composition analysis. We retrospectively analyzed and compared the characteristics of the patients and stones, operation time, stone-free rate, and postoperative complications between the two groups. RESULTS: In the asymptomatic group, mean body mass index (BMI) was significantly higher (25.7±3.8 kg/m² vs. 24.3±2.8 kg/m², p=0.002) and urine pH was significantly lower (5.6±0.9 vs. 5.9±0.9, p=0.013). The ratio of calcium oxalate dihydrate stones was significantly higher in the symptomatic group (5.3% vs. 15.5%, p=0.023). No significant differences were observed in stone characteristics, postoperative outcomes, or complications. In the multivariate logistic regression analysis for predicting variables for asymptomatic renal stones, BMI (odds ratio [OR], 1.144; 95% confidence interval [CI], 1.038-1.260; p=0.007), and urine pH (OR, 0.608; 95% CI, 0.407-0.910; p=0.016) were independent predictive variables for asymptomatic renal stones. CONCLUSIONS: This study demonstrated that thorough medical check-ups are needed for the early detection of renal stones in individuals with a high BMI or low urine pH.

Comparison of the efficacy of the early LI-SWT plus daily tadalafil with daily tadalafil only as penile rehabilitation for postprostatectomy erectile dysfunction.

This study compares the efficacy of the early low-intensity shock wave therapy (LI-SWT) plus daily tadalafil with daily tadalafil only therapy as penile rehabilitation for postprostatectomy erectile dysfunction in patients with prostate cancer who underwent bilateral interfascial nerve-sparing radical prostatectomy (robotic or open). From April 2019 to March 2021, 165 patients were enrolled, and 80 of them successfully completed this prospective study. Daily tadalafil were administered to all the patients. LI-SWT consisted of a total of six sessions. Each session was performed on days 4, 5, 6, and 7, and on the second and fourth weeks after surgery. Each LI-SWT session consisted of 300 shocks at an energy density of 0.09 mJ/mm2 and a frequency of 120 shocks per minute that were delivered at each of the five treatment points for 15 min. Thirty-nine patients were treated with tadalafil-only (group A) while 41 were treated with tadalafil and LI-SWT simultaneously (group B). At postoperative 6 months, the proportion of patients with erection hardness scores (EHS) ≥ 3 (4/39 vs. 12/41) was significantly higher in group B (p = 0.034), and LI-SWT was the only independent factor for predicting EHS ≥ 3 (OR, 3.621; 95% CI, 1.054-12.437; p = 0.041). There were no serious side effects related to early LI-SWT. Early LI-SWT plus daily tadalafil therapy as penile rehabilitation for postprostatectomy erectile dysfunction is thought to be more efficacious than tadalafil only. Further large-scaled randomized controlled trials will be needed to validate these findings.

Current treatment patterns within 1 year after prostate cancer diagnosis in Korean patients over 75 years old: a retrospective multicenter study.

Background: We aimed to evaluate the current status of first-line treatment options for prostate cancer in patients aged ≥75 years in Korea. Materials and methods: The study included 873 patients diagnosed with biopsy-proven prostate cancer at 5 institutions in Korea from January 2009 to December 2018. Inclusion criteria were aged ≥75 years at diagnosis, prostate biopsy with ≥12 cores, and follow-up period ≥1 year. Clinical data were retrospectively collected from electronic medical records. Results: Primary treatment for prostate cancer in patients aged ≥75 years included androgen deprivation therapy (ADT) (n = 614), radical prostatectomy (RP) (n = 114), and radiation therapy (n = 62). Among patients with RP, nine patients received ADT before RP. The RP group was younger with better Eastern Cooperative Oncology Group Performance Status (ECOG PS), lower initial prostate-specific antigen (PSA), Gleason score (GS), max percent positive cores, less positive cores, and less advanced clinical Tumor Node Metastasis (TNM) stage compared with the ADT group. Multivariate analysis showed that age, ECOG PS, and PSA were independent prognostic factors for RP. When the ADT group was classified by therapeutic regimens, the most common therapeutic regimen was maximal androgen blockade (MAB) (n = 571), and leuprolide + bicalutamide (n = 330) was the most common MAB regimen. Multivariate analysis for secondary treatment showed that age, ECOG PS, GS, and clinical N1 or M1 stage were independent predictive factors. Enzalutamide was the most preferred treatment for tertiary treatment. Conclusion: In patients with prostate cancer aged ≥75 years, the most common treatment option was MAB, and the leuprolide + bicalutamide was the most common MAB regimen. Age, ECOG PS, and PSA are the useful indicators of surgical treatment, which increased during the study period. Younger patients with high GS and advanced clinical stage were more likely to undergo secondary treatment.

Asymmetric Contribution of Blastomere Lineages of First Division of the Zygote to Entire Human Body Using Post-Zygotic Variants.

BACKGROUND: In humans, after fertilization, the zygote divides into two 2n diploid daughter blastomeres. During this division, DNA is replicated, and the remaining mutually exclusive genetic mutations in the genome of each cell are called post-zygotic variants. Using these somatic mutations, developmental lineages can be reconstructed. How these two blastomeres are contributing to the entire body is not yet identified. This study aims to evaluate the cellular contribution of two blastomeres of 2-cell embryos to the entire body in humans using post-zygotic variants based on whole genome sequencing. METHODS: Tissues from different anatomical areas were obtained from five donated cadavers for use in single-cell clonal expansion and bulk target sequencing. After conducting whole genome sequencing, computational analysis was applied to find the early embryonic mutations of each clone. We developed our in-house bioinformatics pipeline, and filtered variants using strict criteria, composed of mapping quality, base quality scores, depth, soft-clipped reads, and manual inspection, resulting in the construction of embryological phylogenetic cellular trees. RESULTS: Using our in-house pipeline for variant filtering, we could extract accurate true positive variants, and construct the embryological phylogenetic trees for each cadaver. We found that two daughter blastomeres, L1 and L2 (lineage 1 and 2, respectively), derived from the zygote, distribute unequally to the whole body at the clonal level. From bulk target sequencing data, we validated asymmetric contribution by means of the variant allele frequency of L1 and L2. The asymmetric contribution of L1 and L2 varied from person to person. CONCLUSION: We confirmed that there is asymmetric contribution of two daughter blastomeres from the first division of the zygote across the whole human body.

Role of the JNK Pathway in Bladder Cancer.

Bladder cancer, one of the most frequently diagnosed cancers worldwide, is associated with high morbidity and mortality and a poor prognosis. The bladder cancer types include 1) non-muscle invasive bladder cancer (NMIBC) and 2) muscle invasive bladder cancer (MIBC). Metastases and chemoresistance in MIBC patients are the leading causes of the high death rate. c-Jun N-terminal kinase (JNK) is an important factor for the undifferentiated state of cancer cells. JNK belongs to the mitogen-activated protein kinases (MAPKs) family; it is activated by various extracellular stimuli, such as stress, radiation, and growth factors and mediates diverse cellular functions, such as apoptosis, autophagy, proliferation, invasion, and migration by mediating AKT (Ak strain transforming), ATG (Autophagy related), mTOR (Mammalian target of rapamycin), and caspases 3, 8, and 9. This review describes the JNK-related functions, mechanisms, and signaling in bladder cancer.