Impact of Complete Surgical Resection of Metastatic Lesions in Patients with Advanced Renal Cell Carcinoma in the Era of Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors.

Complete metastasectomy (CM) in metastatic renal cell carcinoma (mRCC) has demonstrated efficacy in the cytokine era, but its effectiveness in the era of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) remains unclear. A multi-institutional database included clinicopathological data of 367 patients with mRCC. Patients were divided into two groups: the CM group and the non-CM group. These two groups were compared before and after propensity score matching (PSM). Cox proportional hazard models were used to detect factors associated with disease-free survival (DFS) and overall survival (OS) from mRCC diagnosis. The CM group showed a significant association with longer overall survival compared to the non-CM group in the PSM-unadjusted cohorts (p < 0.001, hazard ratio 0.49, 95% confidence interval 0.35-0.69), but no superiority was noted in the adjusted cohorts. The median DFS after CM was 24 months, with no significant differences based on relapse timing. Notably, the international metastatic RCC database consortium risk categories and metastatic burden were associated with DFS. This study supports the potential of CM in mRCC management during the TKI/ICI era, although limitations including sample size and selection bias need to be considered.

Enfortumab vedotin following platinum-based chemotherapy and immune checkpoint inhibitors for advanced urothelial carcinoma: response, survival and safety analysis from a multicentre real-world Japanese cohort.

OBJECTIVE: Real-world evidence regarding enfortumab vedotin for unresectable or metastatic urothelial carcinoma is scarce, particularly in Japan. We investigated real-world data focusing on patient background, previous treatments, response, survival and adverse events in patients receiving enfortumab vedotin. METHODS: A multicentre database was used to register 556 patients diagnosed with metastatic urothelial carcinoma from 2008 to 2023; 34 patients (6.1%) treated with enfortumab vedotin were included. Best radiographic objective responses were evaluated using the Response Evaluation Criteria in Solid Tumors (v1.1) during treatments. Overall survival and progression-free survival were estimated (Kaplan-Meier method). Toxicities were reported according to the Common Terminology Criteria for Adverse Events, version 5.0. The relative dose intensity, which could impact oncological outcomes, was calculated. RESULTS: The median number of enfortumab vedotin therapy cycles was 5. The best objective response to enfortumab vedotin was partial response, stable disease and progressive disease in 19 (56%), 5 (15%) and 10 (29%) patients, respectively. The median overall survival and progression-free survival after the first enfortumab vedotin dose were 16 and 9 months, respectively. No significant relationship was observed between survival outcomes after enfortumab vedotin initiation and the enfortumab vedotin relative dose intensity. The median overall survival from first-line platinum-based chemotherapy initiation was 42 months. Twenty-six (76%) patients experienced any grade of enfortumab vedotin-related toxicities; eight (24%) experienced Grades 3-4 toxicities, the most common being skin toxicity (any grade, 47%; Grades 3-4, 12%). CONCLUSIONS: Here, we report real-world evidence for enfortumab vedotin therapy in Japan. Tumour responses and safety profiles were comparable with those of clinical trials on this novel treatment.

[Efficacy of Recombinant Thrombomodulin for Sepsis-Associated Disseminated Intravascular Coagulation Caused by Urinary Tract Infections].

Severe urinary tract infections occasionally cause sepsis and disseminated intravascular coagulation (DIC). We examined the efficacy of recombinant thrombomodulin (rTM) for treating DIC caused by urosepsis. We enrolled 40 patients who were diagnosed with DIC caused by urosepsis at our hospital between April 2018 and May 2022. Twenty-six patients were treated with rTM (rTM group), while 14 patients did not receive rTM (non-rTM group). The DIC score before treatment in the rTM group was significantly higher than that in the non-rTM group (P＜0.01). There was no significant difference in disease-specific survival between the two groups. There was a significant improvement in DIC scores on days 1-3 after administering rTM. However, the duration of DIC in the rTM group was significantly longer than that in the non-rTM group (P＝0.038). The administration of rTM may have benefits in patients with DIC caused by urosepsis.

[Adrenal Hemangiomatous Endothelial Cyst That was Difficult to Differentiate from Adrenal Malignant Tumor: A Case Report].

A 65-year-old woman was referred to our hospital for fever and diagnosed with pyelonephritis. Abdominal computed tomography showed a right adrenal tumor incidentally, that was 6.5 cm in diameter. We could not rule out malignant disease by magnetic resonance imaging examination and performed resection of the right adrenal tumor. The histopathological examination revealed an adrenal hemangiomatous endothelial cyst, and there was no evidence of malignancy. It was difficult to differentiate between adrenal cyst and adrenal cancer in preoperative diagnostic imaging because the tumor contained hemorrhage and necrotic tissue.

Composite pheochromocytoma associated with neurofibromatosis type 1.

Introduction: Composite pheochromocytoma is a rare tumor, occurring in only 3% of pheochromocytomas. We report a case of composite pheochromocytoma with neurofibromatosis type 1. Case presentation: A 42-year-old man was referred to our department for further evaluation of an incidentally detected right adrenal tumor. He was a patient at another hospital for neurofibromatosis type 1. The serum and urinary catecholamine levels exceeded the normal range. Abdominal computed tomography and magnetic resonance imaging showed a 2.8 cm diameter right adrenal tumor, and 123I-metaiodobenzyguanidine scintigraphy showed radioisotope uptake. He was diagnosed with pheochromocytoma and underwent a right laparoscopic adrenalectomy. Histopathological examination revealed that the tumor consisted of a pheochromocytoma and ganglioneuroma. The final diagnosis was composite pheochromocytoma-ganglioneuroma. Five years after surgery, no recurrence was observed. Conclusion: Preoperative diagnosis of composite pheochromocytoma-ganglioneuroma is difficult; therefore, histopathological examination is necessary for a definitive diagnosis. Pheochromocytoma management requires lifelong follow-up.

Switch-maintenance avelumab immunotherapy following first-line chemotherapy for patients with advanced, unresectable or metastatic urothelial carcinoma: the first Japanese real-world evidence from a multicenter study.

OBJECTIVE: To develop the first Japanese real-world evidence of switch-maintenance avelumab in advanced, unresectable or metastatic urothelial carcinoma (aUC). METHODS: A multicenter-derived database registered 505 patients diagnosed with aUC between 2008 and 2021. Of these, 204 patients (40%) were selected and stratified according to the type of therapy used: maintenance avelumab group (27 [5.3%]), second-line (2 L) pembrolizumab group (103 [20%]) and 2 L cytotoxic chemotherapy group (74 [15%]). The progression-free survival and overall survival from the initiation of following therapy were compared. Tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors guideline v1.1 during the treatment period. A detailed analysis was performed in the maintenance avelumab group to investigate possible factors associated with response to avelumab therapy. RESULTS: The maintenance avelumab group had a longer overall survival, not progression-free survival, compared with the other two treatment groups. The median treatment-free interval between the last dose of first-line (1 L) chemotherapy and the initiation of avelumab therapy was 6 weeks (range, 3-22). Disease control rate of maintenance avelumab therapy in patients with a treatment-free interval of ≤6 weeks was higher than that in patients with a treatment-free interval of >6 weeks (77 vs 40%, P = 0.029). The patients showing objective response to 1 L chemotherapy were less likely to experience tumor relapse (4 of 19) after the initiation of avelumab therapy compared with those showing stable disease (7 of 8). CONCLUSIONS: Objective response to 1 L chemotherapy and early induction of maintenance avelumab therapy may be associated with increased benefit from maintenance avelumab therapy.

[Management of Internal Ureteral Stent (Double J-Stent) Occlusion].

Occlusion of internal ureteral stents commonly called double-J (DJ) stent leads to renal dysfunction, urinary tract infection, and difficulty in replacing the stent. We investigated the cause of stent occlusion and whether DJ stent occlusion persisted with change in the type of stent. The internal ureteral stent, Bird® Inlay™ Optima or Boston Scientific® Tria™, was inserted in 43 ureters of 33 patients who underwent replacement more than three times between September 2017 and June 2020. We defined stent occlusion as follows: a guide wire could not be passed through a stent during the replacement. In the first occlusion, the type of stent was changed. In the second occlusion, the stent placement interval was shortened from 12-13 weeks to 6-8 weeks. The presence of urinary stone and insertion of a urethral catheter had a high risk of DJ stent occlusion. Stent occlusion was observed in 20 of the 43 ureters. After the type of stent in 20 ureters with stent occlusion was changed, there were no DJ stent occlusions in 16 of the 20 ureters. Nevertheless, in 4 of the 20 ureters, even if we changed the type, DJ stent occlusion was still present; hence, the replacement interval was shortened. Therefore, changing the type of stent may be a recommended intervention for DJ stent occlusion.

Significant Improvement of Prognosis After the Advent of Immune Checkpoint Inhibitors in Patients with Advanced, Unresectable, or Metastatic Urothelial Carcinoma: A Propensity Score Matching and Inverse Probability of Treatment Weighting Analysis on Real-World Data.

PURPOSE: The treatment landscape for advanced, unresectable, or metastatic urothelial carcinoma (aUC) has shifted substantially since the advent of immune checkpoint inhibitors (ICIs). We investigated the extent to which pembrolizumab therapy is superior to conventional chemotherapy as a second-line treatment. PATIENTS AND METHODS: A multicenter-derived database registered 454 patients diagnosed with aUC between 2008 and 2020. Of these, 94 patients (21%) who received second-line pembrolizumab and 75 (17%) who received second-line chemotherapy but never received third-line or later ICI therapy were included. We compared overall survival (OS) from the initial date of first-line chemotherapy between two groups by adjusting for prognostic factors through propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). The IPTW-adjusted hazard ratio and 95% confidence interval were estimated using a multivariate Cox regression analysis. To identify patients who were more likely to benefit from second-line pembrolizumab than from chemotherapy, we performed a subgroup analysis for OS with an IPTW-adjusted model. RESULTS: The PSM-adjusted comparison showed a significant improvement in the prognosis with second-line pembrolizumab use (P = 0.01). The OS benefit with the advent of pembrolizumab was 8 months (18 months vs 26 months). Multivariable analyses using IPTW adjustment demonstrated that lymph node metastasis (P = 0.001), lung metastasis (P = 0.013), and bone metastasis (P = 0.003) were poor independent prognostic factors, and pembrolizumab use (P = 0.021) was a favorable independent prognostic factor. Subgroup analyses revealed that pembrolizumab was associated with survival benefits over chemotherapy in all subgroups, including young patients (age <70 years), those who received radical surgery, and those without visceral metastasis. CONCLUSION: We demonstrated a significant improvement in prognosis after the advent of pembrolizumab for patients with aUC. ICIs should not be restricted based on patient characteristics.

[IMPACT OF THE SPREAD OF COVID-19 ON THE UROLOGY PRACTICE IN OUR HOSPITAL].

(Purpose) Our hospital plays the role of a prefectural core hospital for COVID-19 and mainly accepts moderate and severely ill patients. In addition, our hospital is also actively responsible for regional emergency medical care, and is designated as a cancer treatment cooperation base hospital. We started accepting patients with COVID-19 in April 2020, and 2 out of 10 wards of our hospital are in operation as exclusive wards for COVID-19 at the time of May 31, 2021. In this study, we compared the effects of the spread of COVID-19 on our urological practice with those before the spread. (Materials and methods) The number of urological operations, their types and average length of stay, the number of outpatients / inpatients, the unit cost of medical treatment income, the referral rate, and the reverse referral rate were calculated based on the in-hospital clinical statistics. (Results) The number of urological operations decreased to 847, 862, and 768 in fiscal year 2018, 2019, and 2020, respectively. There was no significant change in the number of surgeries for malignant tumors in fiscal year 2020, but the number of surgeries for benign diseases decreased. The number of emergency operations tended to increase in fiscal year 2020. The number of urological hospitalized patients in fiscal year 2018, 2019, and 2020 decreased to 653, 690, and 533, and the average length of stay was shortened to 8.4, 8.8, and 8.1 days, respectively. The outpatient and inpatient unit prices per patient when fiscal year 2018 was set to 100 were increasing to 119.5 and 104.9, 133.7 and 119.1 in fiscal year 2019 and 2020, respectively. (Conclusion) It is thought that the spread of COVID-19 has clarified the function and characteristics of our hospital in community medicine.

Assessment of bladder function for stabilizing urinary volume overnight with recording of brain waves (ABSORB study).

OBJECTIVES: The bladder urothelium is not always impermeable. During sleep, the bladder might absorb urine in healthy individuals who sleep through the night. This study aimed to determine whether the bladder absorbs urine by using a method other than ultrasonic scanning and to simultaneously evaluate sleeping conditions. METHODS: Eleven participants (five males, six females) aged 20 to 49 years without lower urinary tract symptoms or urination while sleeping were enrolled. Bladder volume was estimated by studying the relationship between dilution and absorbance of indigo carmine dissolved in urine. A 12F Foley catheter was inserted into the bladder before sleep. Urine samples (5 mL) were extracted at 2, 3, 4, 5, and 6 am sleep stages were monitored with a single-channel portable electroencephalograph device. RESULTS: The estimated bladder volume at 6 am and voided volume immediately after rising were significantly correlated (Spearman's ρ = 0.62, P = .046). Eight participants (three males, five females) showed an absorption pattern of the estimated bladder volume change. In a male participant, the blue dye's strength gradually decreased until 4 am (estimated 859 mL) and increased from 5 am (estimated 455 mL). In another, the blue dye's strength increased at 4 am (estimated 449 mL) vs at 3 am (estimated 757 mL). In all participants, electroencephalograph data demonstrated that sleep was maintained despite having a full bladder. CONCLUSIONS: The bladder absorbs urine and maintains an approximate volume of functional bladder capacity during sleep to avoid incontinence and maintain sleep in adults due to an urge to void urine during the sleep cycle.

Optimal timing of ureteroscopic lithotripsy after the initial drainage treatment and risk factors for postoperative febrile urinary tract infection in patients with obstructive pyelonephritis: a retrospective study.

BACKGROUND: A history of preoperative obstructive pyelonephritis has been reported as a risk factor for febrile urinary tract infection (fUTI) after ureteroscopic lithotripsy (URSL). But there is no clear evidence of risk factors for developing fUTI including the optimal timing of URSL after obstructive pyelonephritis treatment. METHODS: Of the 1361 patients, who underwent URSL at our hospital from January 2011 to December 2017, 239 patients had a history of pre-URSL obstructive pyelonephritis. The risk factors were analyzed by comparing the patients' backgrounds with the presence or absence of fUTI after URSL. The factors examined were age, gender, body mass index, comorbidity, presence or absence of preoperative ureteral stent, stone position, stone laterality, stone size, Hounsfield unit (HU) value on computed tomography scan, history of sepsis during obstructive pyelonephritis, period from antipyresis to URSL, ureteral stenting period, operation time, and presence or absence of access sheath at URSL. In addition, the stone components and renal pelvic urinary culture bacterial species during pre-URSL pyelonephritis were also examined. RESULTS: Post-URSL fUTI developed in 32 of 239 patients (13.4%), and 11 of these 32 cases led to sepsis (34.4%). Univariate analysis showed that stone position, stone maximum HU value, presence of sepsis during obstructive pyelonephritis, period from antipyresis to URSL, pre-URSL ureteral stent placement, operation time were risk factors of fUTI. Stone components and urinary cultures during pyelonephritis were not associated with risk of fUTI. Multivariate analysis showed that renal stone position, pre-URSL ureteral stent placement > 21 days, and operation time > 75 min were independent risk factors of fUTI following the URSL. CONCLUSIONS: F-UTI following the URSL could be avoided by ureteral stent placement period 21 days or less and operation time 75 min or less in patients with obstructive pyelonephritis.

External validation of a genitourinary cancer-specific prognostic scoring system to predict survival for patients with bone metastasis (modified B-FOM scoring model): Comparison with other scoring models in terms of accuracy.

OBJECTIVE: We previously developed genitourinary (GU) cancer-specific scoring system for prediction of survival in patients with bone metastasis (the Bone-Fujimoto-Owari-Miyake [B-FOM] scoring model) based on five prognostic factors: the type of primary tumor (prostate cancer (PCa) vs renal cell carcinoma (RCC) and PCa vs urothelial carcinoma (UC)), poor performance status (PS), visceral metastasis, high Glasgow-prognostic score (GPS), elevated neutrophil-to-lymphocyte ratio (NLR). The aim of this study was to externally validate and further improve the performance of the B-FOM score. METHODS: The external validation cohort comprised 309 patients with GU cancer with bone metastasis from multiple institutions. Clinical factors were analyzed using Kaplan-Meier method and COX regression hazard model. Performance of a modified B-FOM score was compared to that of other scoring models by the Kaplan-Meier method and the area under the curve (AUC) of receiver operating characteristic curves. RESULTS: The median follow-up period of development and validation cohort were 25 and 17 months, respectively. Kaplan-Meier curve demonstrated that the type of primary tumor (RCC and UC vs PCa), poor PS, presence of visceral metastasis, high GPS, elevated NLR were significantly associated with shorter cancer-specific survival. Risk groups were successfully stratified by the modified B-FOM score classification. Moreover, the AUC of the modified B-FOM scoring model for predicting mortality at 6, 12, and 24 months were 0.895, 0.856, and 0.815, respectively, which were the highest among evaluated models. CONCLUSIONS: The B-FOM scoring model is a simple and accurate prediction tool. By using this scoring model at the time of the diagnosis of bone metastasis in patients with GU cancers, an individualized optimal treatment strategy can be selected.

Inhibitory Effect of Orally Administered 5-Aminolevulinic Acid on Prostate Carcinogenesis in the FVB-Transgenic Adenocarcinoma of a Mouse Prostate (FVB-TRAMP) Model.

BACKGROUND: 5-aminolevulinic acid (5-ALA) is a constituent of mitochondrial electron carriers, heme and cytochrome c, which are crucial for aerobic energy metabolism and cell apoptosis. We investigated the chemopreventive efficacy of 5-ALA against prostate cancer using the FVB-transgenic adenocarcinoma of mouse prostate (FVB-TRAMP) model. METHODS: Samples were collected from 24 FVB-TRAMP mice at 12 and 20 weeks of age (named the first and second sets, respectively). Sixteen mice (from the first set) were randomly allocated into 3 treatment groups: 1) control (no treatment), 2) low dose of 5-ALA (30 mg/kg/day), and 3) high dose of 5-ALA (300 mg/kg/day). Similarly, 8 mice were divided into 2 treatment groups: 1) control and 2) high dose of 5-ALA (300 mg/kg/day). 5-ALA was orally administered to mice before cancer onset, from 6 weeks of age. RESULTS: In the control group, prostate cancer was pathologically detected in 33 and 50 % of mice at 12 and 20 weeks, respectively, while 25% of 12-week old mice in the low-dose group were affected and none of the high-dose group mice developed prostate cancer. Immunohistochemical analysis showed higher expression of cytochrome c oxidase subunit 4 (COX4) in the prostate gland of the high-dose group compared to the control (P = 0.018). Similarly, enzyme-linked immunosorbent assay using lysed prostate tissue revealed higher amounts of cytochrome c in the prostate of the high-dose group compared to the control (P = 0.021). Furthermore, western blot analysis showed higher level of cleaved caspase-3 in mice in the high-dose group diagnosed with high-grade prostatic intraepithelial neoplasia. CONCLUSION: Our results suggest that oral 5-ALA may support the functional expression of mitochondrial cytochrome c and COX4, leading to caspase 3-dependent apoptosis in carcinogenesis in FVB-TRAMP mice. Future clinical studies are warranted to confirm the chemopreventive value of 5-ALA in prostate carcinogenesis. 
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A Japanese man with spina bifida who successfully fathered a child following fertility treatment.

INTRODUCTION: Spina bifida is a congenital anomaly caused by a neural tube closure defect that may result in sexual dysfunction. Sexual dysfunction and infertility are prevalent in spina bifida patients but have been scarcely reported. CASE PRESENTATION: We report the case of a 36-year-old man with spina bifida and mild-moderate erectile dysfunction. He could experience erection and ejaculation. He got married at the age of 28 years, but his wife was unable to conceive for 2 years thereafter. Semen analyses revealed that semen volume, sperm density, and sperm motility rate were below normal levels. It was concluded that natural conception would be difficult, and assisted reproductive strategies were planned. After 4 years, his wife conceived through intracytoplasmic sperm injection and gave birth to a healthy baby. CONCLUSION: Fertility treatment, including intracytoplasmic sperm injection, is a useful therapeutic method for male patients with spina bifida who desire to father a child.

Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse Model.

Chemotherapy-induced adverse effects can reduce the relative dose intensity and quality of life. In this study, we investigated the potential benefit of supplementary anamorelin and 5-aminolevulinic acid (5-ALA) as preventive interventions against a gemcitabine and cisplatin (GC) combination chemotherapy-induced adverse effects in a mouse model. Non-cancer-bearing C3H mice were randomly allocated as follows and treated for 2 weeks-(1) non-treated control, (2) oral anamorelin alone, (3) oral 5-ALA alone, (4) gemcitabine and cisplatin (GC) chemotherapy, (5) GC plus anamorelin, and (6) GC plus 5-ALA. GC chemotherapy significantly decreased body weight, food intake, skeletal muscle mass and induced severe gastric mucositis, which resulted in decreased ghrelin production and blood ghrelin level. The supplementation of oral anamorelin to GC chemotherapy successfully mitigated decrease of food intake during the treatment period and body weight loss at day 8. In addition, analysis of the resected muscles and stomach revealed that anamorelin suppressed chemotherapy-induced skeletal muscle atrophy by mediating the downregulation of forkhead box protein O-1 (FOXO1)/atrogin-1 signaling and gastric damage. Our findings suggest the preventive effect of anamorelin against GC combination chemotherapy, which was selected for patients with some types of advanced malignancies in clinical practice.

Clinical Impact of Sarcopenia and Inflammatory/Nutritional Markers in Patients with Unresectable Metastatic Urothelial Carcinoma Treated with Pembrolizumab.

Sarcopenia is a muscle loss syndrome known as a risk factor of various carcinomas. The impact of sarcopenia and sarcopenia-related inflammatory/nutritional markers in metastatic urothelial carcinoma (mUC) treated with pembrolizumab was unknown, so this retrospective study of 27 patients was performed. Psoas muscle mass index (PMI) was calculated by bilateral psoas major muscle area at the L3 with computed tomography. The cut-off PMI value for sarcopenia was defined as ≤6.36 cm2/m2 for men and ≤3.92 cm2/m2 for women. Neutrophil-to-lymphocyte ratio (NLR) ≥ 4.0 and sarcopenia correlated with significantly shorter progression-free survival (PFS) (hazard ratio (HR) 3.81, p = 0.020; and HR 2.99, p = 0.027, respectively). Multivariate analyses identified NLR ≥ 4.0 and sarcopenia as independent predictors for PFS (HR 2.89, p = 0.025; and HR 2.79, p = 0.030, respectively). Prognostic nutrition index < 45, NLR ≥ 4.0 and sarcopenia were correlated with significantly worse for overall survival (OS) (HR 3.44, p = 0.046; HR 4.26, p = 0.024; and HR 3.92, p = 0.012, respectively). Multivariate analyses identified sarcopenia as an independent predictor for OS (HR 4.00, p = 0.026). Furthermore, a decrease in PMI ≥ 5% in a month was an independent predictor of PFS and OS (HR 12.8, p = 0.008; and HR 6.21, p = 0.036, respectively). Evaluation of sarcopenia and inflammatory/nutritional markers may help in the management of mUC with pembrolizumab.

Disabled Homolog 2 (DAB2) Protein in Tumor Microenvironment Correlates with Aggressive Phenotype in Human Urothelial Carcinoma of the Bladder.

Disabled homolog-2 (DAB2) has been reported to be a tumor suppressor gene. However, a number of contrary studies suggested that DAB2 promotes tumor invasion in urothelial carcinoma of the bladder (UCB). Here, we investigated the clinical role and biological function of DAB2 in human UCB. Immunohistochemical staining analysis for DAB2 was carried out on UCB tissue specimens. DAB2 expression levels were compared with clinicopathological factors. DAB2 was knocked-down by small interfering RNA (siRNA) transfection, and then its effects on cell proliferation, invasion, and migration, and changes to epithelial-mesenchymal transition (EMT)-related proteins were evaluated. In our in vivo assays, tumor-bearing athymic nude mice subcutaneously inoculated with human UCB cells (MGH-U-3 or UM-UC-3) were treated by DAB2-targeting siRNA. Higher expression of DAB2 was associated with higher clinical T category, high tumor grade, and poor oncological outcome. The knock-down of DAB2 decreased both invasion and migration ability and expression of EMT-related proteins. Significant inhibitory effects on tumor growth and invasion were observed in xenograft tumors of UM-UC-3 treated by DAB2-targeting siRNA. Our findings suggested that DAB2 expression was associated with poor prognosis through increased oncogenic properties including tumor proliferation, migration, invasion, and enhancement of EMT in human UCB.

A Potential Application of Dynamic Contrast-Enhanced Magnetic Resonance Imaging Combined with Photodynamic Diagnosis for the Detection of Bladder Carcinoma in Situ: Toward the Future 'MRI-PDD Fusion TURBT'.

The detection of carcinoma in situ (CIS) is essential for the management of high-risk non-muscle invasive bladder cancers. Here, we focused on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) combined with photodynamic diagnosis (PDD) for the detection of CIS. A total of 45 patients undergoing pre-surgical DCE-MRI and PDD-assisted endoscopic surgery accompanied by biopsies of the eight segmentations were analyzed. Immunohistochemical analysis of the biopsies revealed hypervascularity of CIS lesions, a cause of strong submucosal contrast-enhancement. It was found that 56 (16.2%) of 344 biopsies had pathologically proven CIS. In the DCE-MRI, the overall sensitivity and specificity for detecting CIS were 48.2% and 81.9%, respectively. We set out two different combinations of PDD and DCE-MRI for detecting CIS. Combination 1 was positive when either the PDD or DCE-MRI were test-positive. Combination 2 was positive only when both PDD and DCE-MRI were test-positive. The overall sensitivity of combinations 1 and 2 were 75.0% and 37.5%, respectively (McNemar test, vs PDD alone; p = 0.041 and p < 0.001, respectively). However, the specificity was 74.0% and 91.7%, respectively (vs PDD alone; both p < 0.001). Our future goal is to establish 'MRI-PDD fusion transurethral resction of the bladder tumor (TURBT), which could be an effective therapeutic and diagnostic approach in the clinical management of high-risk disease.

Supplementary granulocyte macrophage colony-stimulating factor to chemotherapy and programmed death-ligand 1 blockade decreases local recurrence after surgery in bladder cancer.

Despite advances and refinements in surgery and perioperative chemotherapy, there are still unmet medical needs with respect to radical cystectomy for muscle-invasive bladder cancer (MIBC). We investigated the potential benefit of supplementary granulocyte macrophage colony-stimulating factor (GM-CSF) to chemoimmunotherapy with programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis blockade and standard neoadjuvant chemotherapy in bladder cancer. We inoculated 2 × 105 MBT2 cells s.c. in C3H mice to create a syngeneic animal model of local recurrence (LR). When the tumor diameter reached 12 mm, the mice were allocated randomly as follows: (i) non-treated control (vehicle only); (ii) anti-mPD-L1 monotherapy; (iii) mGM-CSF monotherapy; (iv) anti-mPD-L1 plus mGM-CSF; (v) gemcitabine and cisplatin (GC); (vi) GC plus anti-mPD-L1; (vii) GC plus mGM-CSF; and (viii) GC plus anti-mPD-L1 plus mGM-CSF. After completing 2-week neoadjuvant therapy, tumors were resected for resection margin evaluation and immunohistochemical staining and blood was collected for flow cytometry and ELISA. Operative wounds were sutured, and the operative site was monitored to detect LR. Addition of anti-mPD-L1 and mGM-CSF to neoadjuvant GC chemotherapy enhanced the antitumor effect and reduced positive resection margins (50% vs 12.5%). Combination of GC, anti-mPD-L1, and mGM-CSF resulted in longer LR-free survival and cancer-specific survival compared to those in other groups. These effects involved an immunotherapy-related decrease in oncological properties such as tumor invasion capacity and epithelial-mesenchymal transition. mGM-CSF significantly decreased the accumulation of myeloid-derived suppressor cells in both the blood and tumor microenvironment and blood interleukin-6 levels. Supplementary GM-CSF to neoadjuvant GC plus PD-L1 blockade could decrease LR after radical surgery by immune modulation in the blood and tumor microenvironment.

Evaluation of Preoperative Abdominal Adipose Tissue-, Inflammation-, Muscle Mass-, and Nutritional Status-based Prognostic Markers to Assess Renal Dysfunction in Living Kidney Donors.

BACKGROUND: Living kidney donors (LKDs) are at high risk of renal dysfunction after undergoing a donor nephrectomy (DN), resulting in poor prognosis associated with the development of cardiovascular or cerebrovascular disease. Decreasing this risk can improve the survival rate of LKDs. We investigated the effects of preoperative conditions in LKDs on renal dysfunction after DN using abdominal adipose tissue, inflammation, nutritional status, and muscle mass as markers for this assessment. METHODS: Our retrospective study included 79 LKDs. Body composition markers were assessed using preoperative unenhanced computed tomographic images. Inflammation- and nutritional status-based markers were assessed using preoperative laboratory blood tests. The association between each marker was investigated, and prognostic markers for renal dysfunction after DN were identified. RESULTS: The LKDs in this cohort comprised 30 men and 49 women. The median age at the time of DN and the preoperative estimated glomerular filtration rate were 58 years and 81.9 mL/min/1.73 m2, respectively. Abdominal subcutaneous adipose tissue and muscle mass significantly differed between the sexes. Each adipose tissue-, inflammation-, nutritional status-, and muscle mass-based marker showed an association with each other. Abdominal visceral adipose tissue and nutritional status could be independent prognostic markers for renal dysfunction after DN. CONCLUSIONS: Our findings suggest that the preoperative condition of LKDs (assessed using specific markers such as abdominal visceral adipose tissue mass per volume and nutritional status) could affect renal dysfunction after DN. Optimal preoperative management can lead to better outcomes in LKDs. Further research is needed to establish appropriate exercise programs and nutritional interventions.