Peripheral neuropathy and nerve electrophysiological changes with enfortumab vedotin in patients with advanced urothelial carcinoma: a prospective multicenter cohort study.

BACKGROUND: Enfortumab vedotin is a novel antibody-drug conjugate used as a third-line therapy for the treatment of urothelial cancer. We aimed to elucidate the effect of enfortumab vedotin-related peripheral neuropathy on its efficacy and whether enfortumab vedotin-induced early electrophysiological changes could be associated with peripheral neuropathy onset. METHODS: Our prospective multicenter cohort study enrolled 34 patients with prior platinum-containing chemotherapy and programmed cell death protein 1/ligand 1 inhibitor-resistant advanced urothelial carcinoma and received enfortumab vedotin. The best overall response, progression-free survival, overall survival, and safety were assessed. Nerve conduction studies were also performed in 11 patients. RESULTS: The confirmed overall response rate and disease control rate were 52.9% and 73.5%, respectively. The median overall progression-free survival and overall survival were 6.9 and 13.5 months, respectively, during a median follow-up of 8.6 months. The patients with disease control had significantly longer treatment continuation and overall survival than did those with uncontrolled disease. Peripheral neuropathy occurred in 12.5% of the patients. The overall response and disease control rates were 83.3% and 100%, respectively: higher than those in patients without peripheral neuropathy (p = 0.028 and p = 0.029, respectively). Nerve conduction studies indicated that enfortumab vedotin reduced nerve conduction velocity more markedly in sensory nerves than in motor nerves and the lower limbs than in the upper limbs, with the sural nerve being the most affected in the patients who developed peripheral neuropathy (p = 0.011). CONCLUSION: Our results indicated the importance of focusing on enfortumab vedotin-induced neuropathy of the sural nerve to maximize efficacy and improve safety.

Photodynamic diagnostic ureteroscopy using the VISERA ELITE video system for diagnosis of upper-urinary tract urothelial carcinoma: a prospective cohort pilot study.

BACKGROUND: The advantages of photodynamic diagnostic technology using 5-aminolevulinic acid (ALA-PDD) have been established. The aim of this prospective cohort study was to evaluate the usefulness of ALA-PDD to diagnose upper tract urothelial carcinoma (UT-UC) using the Olympus VISERA ELITE video system. METHODS: We carried out a prospective, interventional, non-randomized, non-contrast and open label cohort pilot study that involved patients who underwent ureterorenoscopy (URS) to detect UT-UC. 5-aminolevulinic acid hydrochloride was orally administered before URS. The observational results and pathological diagnosis with ALA-PDD and traditional white light methods were compared, and the proportion of positive subjects and specimens were calculated. RESULTS: A total of 20 patients were enrolled and one patient who had multiple bladder tumors did not undergo URS. Fifteen of 19 patients were pathologically diagnosed with UT-UC and of these 11 (73.3%) were ALA-PDD positive. Fourteen of 19 patients were ALA-PDD positive and of these 11 were pathologically diagnosed with UC. For the 92 biopsy specimens that were malignant or benign, the sensitivity for both traditional white light observation and ALA-PDD was the same at 62.5%, whereas the specificities were 73.1% and 67.3%, respectively. Of the 38 specimens that were randomly biopsied without any abnormality under examination by both white light and ALA-PDD, 11 specimens (28.9%) from 5 patients were diagnosed with high grade UC. In contrast, four specimens from 4 patients, which were negative in traditional white light observation but positive in ALA-PDD, were diagnosed with carcinoma in situ (CIS). CONCLUSIONS: Our results suggest that ALA-PDD using VISERA ELITE is not sufficiently applicable for UT-UC. Nevertheless, it might be better particularly for CIS than white light and superior results would be obtained using VISERA ELITE II video system. TRIAL REGISTRATION: The present clinical study was approved by the Okayama University Institutional Review Board prior to study initiation (Application no.: RIN 1803-002) and was registered with the UMIN Clinical Trials Registry (UMIN-CTR), Japan (Accession no.: UMIN000031205).

6p21 translocation renal cell carcinoma: A case report.

6p21 translocation renal cell carcinoma (RCC) was newly classified in the WHO 2016 classification as a subtype of microphthalmia-associated transcription factor (MIT) family translocation RCC.A 42-year-old man was referred to our hospital with an asymptomatic solid mass in the right kidney identified during routine medical checkup. Computed tomography (CT) revealed a 14-mm buried-type solid mass accompanied by punctate calcification. CT-guided biopsy suggested clear-cell carcinoma. He underwent robotic-assisted partial nephrectomy. Pathological findings revealed 6p21 translocation RCC based on diffuse nuclear immunoreactivity for TFEB and TFEB gene rearrangement in tumor cells by FISH analysis.

Comparison of longitudinal health-related quality-of-life outcomes between anterior and posterior surgical approaches to robot-assisted radical prostatectomy.

Increasingly, studies have explored health-related quality-of-life (HRQOL) outcomes after robot-assisted radical prostatectomy (RARP). Nevertheless, no study has compared differences between anterior and posterior surgical approaches. The aim of this study is to assess differences of HRQOL following these two surgical approaches. From January 2012 to September 2017, 653 patients underwent RARP at our institution. We included patients who underwent operations by three experienced surgeons with interchangeability of role as console operator, and who could evaluate preoperatively the Expanded Prostate Cancer Index Composite (EPIC) score. Patients treated with neoadjuvant hormonal therapy were excluded. HRQOL was assessed using the EPIC score, and the questionnaire was administered at 6 timepoints: the baseline survey was conducted within 3 months before the surgery, and follow-up surveys were conducted at 2 weeks, 1, 3, 6, and 12 months after surgery. We defined the minimal clinically important difference (MCID) as half the standard deviation of the baseline score for each domain. A total of 201 patients were included in this retrospective study. Of these, 146 patients underwent RARP using an anterior surgical approach and 55 patients underwent a posterior approach. The clinical characteristics had no significant differences except for median prostate volume between the anterior and posterior groups (27 ml vs 29 ml, p = 0.049). There were no significant differences between the two groups in score decline beyond the MCID in any domain at any timepoint. Our study demonstrates no significant differences in HRQOL between anterior and posterior surgical approaches to RARP.

Favorable long-term oncological and urinary outcomes of incidental prostate cancer following holmium laser enucleation of the prostate.

The aim of the present study was to investigate the impact of incidental prostate cancer (IPCa), which was diagnosed by holmium laser enucleation of the prostate (HoLEP), on long-term oncological and functional outcomes. A total of 482 patients who underwent HoLEP for benign prostatic hyperplasia (BPH) between 2008 and 2016 at our institution were retrospectively reviewed. We defined IPCa as prostate cancer (PCa) according to the enucleated tissue of transitional zone. Therefore, 64 patients were excluded for the following reasons: Prostate-specific antigen (PSA) ≥4.0 ng/ml and no prostate biopsy (n=46); and PSA ≥4.0 ng/ml and diagnosed with PCa by prostate biopsy performed during HoLEP (n=18). Notably, 418 patients were included in the study and divided into two groups: The BPH group and the IPCa group. For 5 years, postoperative PSA and functional outcomes were evaluated. Of 418 patients, 25 (6%) were diagnosed with IPCa by HoLEP, 21 patients (84%) had a Gleason score ≤6 and 5 patients (20%) received adjuvant therapy for PCa following HoLEP. No significant differences were observed between groups for preoperative PSA, PSA density, or urinary and sexual function outcomes; however, age at the time of HoLEP significantly differed between groups (71.7 vs. 75.5 years, P=0.026). Long-term (5-year) urinary outcomes demonstrated sustained improvement. Postoperative PSA increased gradually in the IPCa group (3-year, P=0.033; 4-year, P=0.037); International Index of Erectile Function 5 conversely decreased (5-year, P=0.068). According to the present results, if standard PSA screening and prostate biopsy are performed, watchful waiting for IPCa is feasible, and IPCa does not impact on 5-year urinary outcomes.

Clinical impact of abdominal fat distribution measured by 3-D computed tomography volumetry on post-transplant renal function in recipients after living kidney transplantation: a retrospective study.

BACKGROUND: Excessive visceral fat may decrease renal function because of metabolic derangements. The aim of this study was to evaluate the impact of abdominal fat distribution on renal function of recipients after kidney transplantation using the visceral adipose tissue (VAT)/subcutaneous adipose tissue (SAT) ratio. METHODS: Seventy-nine patients underwent living kidney transplantation from 2009 to 2017. Patients without a correct measurement of VAT and SAT, follow-up of < 6 months, or with kidney transplant rejection or a virus infection were excluded. VAT and SAT were calculated automatically by 3-D volume analyzer software in recipients prior to living kidney transplantation. Our primary aim was to identify abdominal fat distribution measured by CT associated with renal dysfunction (estimate glomerular filtration rate; eGFR < 45) at 6 month post renal transplantation in recipient. RESULTS: Fifty-eight living kidney recipients were included in this retrospective study: 30 for the high VAT/SAT ratio group; 28 for the VAT/SAT low group. Multiple logistic regression analysis showed the VAT/SAT ratio and pre-donor eGFR were associated with eGFR < 45 ml/min/1.73 m2. An increase in VAT/SAT ratio was associated independently with the incidence of decreased renal function. CONCLUSION: This finding indicates that adipose tissue distribution is an important predictor of the outcome of living kidney transplantation in recipients.

Loss of psoas major muscle volume during systemic chemotherapy is related to worse prognosis in testicular cancer.

OBJECTIVE: In several cancers, the loss of skeletal muscle is well associated with oncological outcome. However, its effect is unknown in testicular cancer. This study evaluated the prognostic impact of psoas major muscle volume loss during systemic chemotherapy. METHODS: This was a retrospective study of patients who underwent chemotherapy from 2008 to 2017. Psoas major muscle volume was calculated by volume analyzer software, and its loss was calculated during systemic chemotherapy. The patients were divided according to muscle volume loss: Group 1 (<20%) and Group 2 (≥20%). The losses were compared with Kaplan-Meier curves, and a Cox proportional hazard model was applied to test predictors of poor prognosis. RESULTS: Fifty patients were included. Seventeen were classified into Group 1, and 33 into Group 2. The Kaplan-Meier curves revealed that the progression-free and the overall survival of Group 1 were significantly better than those of Group 2 (P = 0.002, P = 0.03, respectively). A multivariate analysis identified psoas major muscle volume loss as a significant and independent predictor of poor prognosis. CONCLUSIONS: Patients with psoas major muscle volume loss during chemotherapy had a significantly worse prognosis than those without loss.

Use of single-dose perioperative antimicrobial therapy is acceptable in recipients of living-donor renal transplants in the rituximab era.

OBJECTIVE: The aim of this study was to evaluate the efficacy of single-dose perioperative antimicrobial therapy as infection prophylaxis in recipients of living-donor renal transplants in the rituximab era. PATIENTS AND METHODS: Between 2009 and 2017, 84 recipients underwent living-donor renal transplantation (LDRT) at Okayama University Hospital; 3 with vascular/urinary complications requiring additional surgery were excluded from this analysis. Data including recipient characteristics, antimicrobial prophylaxis and administration of rituximab were retrospectively examined for an association with perioperative infections. Prophylactic antimicrobial agents, selected according to the Results of preoperative urine cultures, were administered just before incision. Perioperative infections, which consisted of surgical site infections, remote infections, and urinary tract infections, were defined as a positive culture indicating required administration of additional antimicrobial agents. RESULTS: Among the 81 recipients, prophylactic cefazolin, ampicillin/sulbactam, and others were administered to 66 (82%), 13 (16%), and 2 (3%) recipients, respectively. Twenty-one (26%) received single-dose antimicrobial prophylaxis, while 60 (74%) received multiple doses up to 7 days. Rituximab was used in 59 (72.8%) recipients. The incidence of urinary tract infection, surgical site infection and remote infection was 13 (16%), 1 (1%), and 0, respectively. Univariate analysis could not demonstrate any significant risk factors for postoperative urinary tract infections, including a single dose vs multiple doses of antimicrobial therapy (P = 0.069) and administration of rituximab (P = 0.717). CONCLUSIONS: Our data suggest that the use of single-dose perioperative antimicrobial therapy is acceptable for prophylaxis of infections in patients undergoing LDRT, even in the rituximab era.

Burned-out Prostate Cancer ? Primary Metastatic Cancer Not Detected on Repeat Biopsy.

Metastatic prostate cancer (PCa) cases that cannot be detected on repeat prostate biopsy are extremely rare. Our patient was a 51-year-old Japanese man diagnosed as metastatic PCa by histopathological examination of lesions obtained bone biopsy and lymph node dissection. The primary tumor was not detected after repeated prostate biopsy. Metastatic PCa was diagnosed based on immunohistochemical staining: PSA, AR, P504S, and NKX3.1 of bone and lymph node with metastasis. We speculate that the primary PCa was "burned-out," demonstrating remote metastases with no apparent primary tumor in the prostate. Burned-out PCa may be difficult to diagnose and treat due to its rarity.

Red nodular melanoma of the penile foreskin: A case report and literature review.

The penis is an extremely rare primary site for malignant melanomas, and the clinical presentation may vary greatly. We herein present the case of a 71-year-old male patient who presented with a 6-year history of two slow growing, asymptomatic red macules on the penile foreskin. On physical examination, the mobility of the foreskin was good, and there was no metastasis on computed tomography and magnetic resonance imaging. The patient underwent segmental circumcision for treatment and histological diagnosis, and the histological examination revealed a malignant melanoma. As cancer cells were identified at the edge of the tissue specimen and computed tomography-positron emission tomography revealed increased uptake of 18F-fluorodeoxyglucose in the penis, wider resection and a right sentinel lymph node biopsy were performed; both specimens came back negative. Two years after the surgery, there has been no evidence of locoregional recurrence or distant metastases. The aim of this report is to alert physicians to include melanoma in the differential diagnosis of red-pigmented lesions of the penile foreskin.

Ureteroscopic Management of Large ≥2 cm Upper Tract Urothelial Carcinoma: A Comprehensive 23-Year Experience.

OBJECTIVE: To evaluate the effectiveness of ureteroscopy (URS) with laser ablation as an alternative treatment for upper tract urothelial carcinoma (UTUC) lesions larger than 2 cm. Traditionally, patients with large UTUC are treated with radical nephroureterectomy (RNU). However, in patients with pre-existing renal disease, a solitary kidney, or those who decline RNU, management of UTUC may prove challenging METHODS: An institutional database review identified 80 patients with biopsy proven low-grade UTUC who had at least one lesion larger than 2 cm. We collected clinical data including demographics, operative parameters, and pathologic features. Follow-up for all patients was standardized and included cystoscopy and URS every 3 months until clear, every 6 months through the fifth year, and yearly thereafter. We calculated rates of recurrence, progression, and overall survival. RESULTS: In total, 86 unique lesions ≥2cm were identified in the 80 qualifying patients; mean tumor size was 3.04 cm. Median follow-up was 43.6 months. During follow-up of patients treated curatively, 90.5% of tumors had ipsilateral recurrence and 31.7% progressed in grade at a median of 26.3 months. RNU was performed in 16 patients (20%); mean time to surgery was 23.2 months. Overall survival was 75%, and cancer specific survival was 84% at 5-year follow-up. CONCLUSION: Under strict surveillance, ureteroscopic management of large (≥ 2cm) UTUC lesions is a viable treatment alternative to RNU. While recurrence is common, URS can potentially preserve renal units in patients with large lesions.

Analysis of Progranulin-Mediated Akt and MAPK Activation.

Progranulin has emerged in recent years as an important regulator of various biological functions including cell proliferation, wound healing, motility, and protection from apoptosis. Progranulin is also critical for transformation as established in several cancer models.Progranulin biological responses elicit through the activation of the Akt and MAPK pathways, which are critical for progranulin downstream signaling.In this chapter various experimental approaches aiming at detecting progranulin-mediated Akt and MAPK activation will be discussed.

Renal Function after Nephrectomy Influences the Risk of Cardiovascular Events.

We retrospectively analyzed the factors related to postoperative cardiovascular (CV) events in patients undergoing partial nephrectomy (PN) or radical nephrectomy (RN) for clinical T1 renal cell carcinoma (RCC). We identified 570 patients who underwent PN or RN for T1 renal cell carcinoma between January 1998 and December 2009 at our institution and related hospitals. We determined the cumulative incidence rate of CV events and overall survival (OS) using Kaplan-Meier survival curves with a log-rank test, and we evaluated the risk for an increase in CV events and OS using Cox proportional hazard regression. Of the 570 patients, 171 underwent PN and 399 underwent RN. The type of surgery was not significantly related with CV events. The only factor that significantly increased the risk of CV events in both the univariate (HR 2.67, p=0.006) and multivariate analyses (HR 2.14, p=0.044) was a postoperative estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m2. Postoperative eGFR was also a significant risk factor for OS in the univariate analysis (HR 2.38, p=0.0104), but not in the multivariate model. Postoperative renal function was a significant independent predictor of the incidence of subsequent CV events.

Simultaneous Bilateral Ureteral Calculi: A New Paradigm for Management.

OBJECTIVE: To define the need for emergent intervention between patients with simultaneous bilateral ureteral calculi (SBUC) compared to unilateral ureteral calculi (UUC). Patients with SBUC represent a potential urological emergency due to possible anuria or electrolyte imbalance. While conventional practice mandates immediate intervention in these patients, little data exist to define the rate of these events. METHODS: Records of all patients with ureteral stones treated ureteroscopically over an 11-year period were reviewed to identify those with SBUC. Patient presenting characteristics, time from diagnosis to intervention, and postoperative outcomes were noted. To determine the need for emergent intervention, we compared metabolic and infectious parameters between SBUC patients and age- and sex-matched patients with UUC. RESULTS: A total of 3800 patients presented with ureteral calculi including 42 (1.1%) with SBUC. Two-thirds of patients with SBUC had an established diagnosis of nephrolithiasis. Among the 42 patients with SBUC, 11 (26.2%) were considered emergent due to metabolic (5 of 11, 45.5%), infectious (1 of 11, 9.1%), or both metabolic and infectious indications (5 of 11, 45.5%). No patients required acute dialysis before surgical intervention. Compared to patients with UUC, those with SBUC were significantly more likely to require emergent management (P = .03, odds ratio 2.3). Univariate and multivariate analyses showed this to be due to anuria (P = .001) and acidosis (P = .003). CONCLUSION: SBUC is an uncommon condition and, in this series, only the minority of patients presented emergently. Therefore, patients with SBUC can often be managed electively if counseled on clinical signs warranting emergent medical attention. Appropriately selected patients have excellent outcomes following single stage bilateral ureteroscopy.

Prognostic impact of bleomycin pulmonary toxicity on the outcomes of patients with germ cell tumors.

Bleomycin pulmonary toxicity (BPT) has been well described in patients with germ cell tumors treated with bleomycin etoposide and cisplatin chemotherapy (BEP). To assess the prognostic impact of BPT, we retrospectively identified 52 patients who underwent bleomycin etoposide and cisplatin chemotherapy from 2008 to 2017 in our institution, and evaluated the risk factors of BPT and its effect on prognosis. Patients who had received chemotherapy at another institution were excluded. BPT was defined as bleomycin discontinuation in response to pulmonary function test decline, pulmonary symptoms, or interstitial pneumonia on computed tomography without infection. We divided the patients into two groups according to this definition: BPT and non-BPT. Their median age was 34.2 years, and their median body mass index was 22.8 kg/m2. Twenty patients had a smoking history, 37 were diagnosed with non-seminoma, and 20 had lung metastasis. The median cumulative bleomycin dose was 270 mg/body. Fifteen patients were classified into the BPT group and 37 into the non-BPT group. Only body mass index < 22 was identified as a predictor of BPT in multivariable logistic models. Age or use of granulocyte-colony stimulating factor did not have a significant impact. Kaplan-Meier analysis revealed that the presence of BPT had no significant impact on either 5-year overall survival or progression-free survival. Lower body mass index can increase the risk of BPT in patients with germ cell tumors undergoing BEP. However, discontinuation of bleomycin with BPT does not adversely influence the survival outcomes.

Oncological impact of neoadjuvant hormonal therapy on permanent iodine-125 seed brachytherapy in patients with low- and intermediate-risk prostate cancer.

OBJECTIVES: To determine whether neoadjuvant hormonal therapy improves oncological outcomes of patients with localized prostate cancer treated with permanent brachytherapy. METHODS: Between January 2004 and November 2014, 564 patients underwent transperineal ultrasonography-guided permanent iodine-125 seed brachytherapy. We retrospectively analyzed low- or intermediate-risk prostate cancer based on the National Comprehensive Cancer Network guidelines. The clinical variables were evaluated for influence on biochemical recurrence-free survival, progression-free survival, cancer-specific survival and overall survival. RESULTS: A total of 484 patients with low-risk (259 patients) or intermediate-risk disease (225 patients) were evaluated. Of these, 188 received neoadjuvant hormonal therapy. With a median follow up of 71 months, the 5-year actuarial biochemical recurrence-free survival rates of patients who did and did not receive neoadjuvant hormonal therapy were 92.9% and 93.6%, respectively (P = 0.2843). When patients were stratified by risk group, neoadjuvant hormonal therapy did not improve biochemical recurrence-free survival outcomes in low- (P = 0.8949) or intermediate-risk (P = 0.1989) patients. The duration or type of hormonal therapy was not significant in predicting biochemical recurrence. In a multivariate analysis, Gleason score, pretreatment prostate-specific antigen, clinical T stage, and prostate dosimetry, primary Gleason score and positive core rate were significant predictive factors of biochemical recurrence-free survival, whereas neoadjuvant hormonal therapy was insignificant. Furthermore, neoadjuvant hormonal therapy did not significantly influence progression-free survival, cancer-specific survival or overall survival. CONCLUSIONS: In patients with low- or intermediate-risk disease treated with permanent prostate brachytherapy, neoadjuvant hormonal therapy does not improve oncological outcomes. Its use should be restricted to patients who require prostate volume reduction.

Prospective randomized controlled trial of postoperative early intravesical chemotherapy with pirarubicin (THP) for solitary non-muscle invasive bladder cancer comparing single and two-time instillation.

PURPOSE: Single immediate intravesical instillation of chemotherapy after transurethral resection of bladder tumor (TURBT) has been the gold standard treatment for patients with low- and intermediate-risk non-muscle invasive bladder cancer (NMIBC). Herein, we conducted a multicenter prospective randomized controlled trial in Japan, comparing recurrence-free survival between single and two-time instillation of pirarubicin (THP) for solitary NMIBC. METHODS: Between 2005 and 2009, 257 patients with solitary NMIBC were enrolled and randomized to single instillation of THP (30 mg/50 mL) immediately after TURBT (Group A) or two-time instillation of THP immediately after and 1 day after TURBT (Group B). The primary endpoint was recurrence-free survival. Secondary endpoints included rates of recurrence and adverse effects, including hematuria, micturition pain, difficult urination, pollakiuria, systemic symptoms, and other complications. This study was registered as UMIN C000000266. RESULTS: Of 257 patients, 99 in Group A and 102 in Group B could be evaluated for recurrence. Median follow-up was 71 months. The overall recurrence rate was 39 and 31%, respectively (p = 0.2704). Although the 5-year recurrence-free survival rates were 55.9% and 67.7% in groups A and B, respectively, the difference between groups was not significant (p = 0.2031). No significant differences in adverse effects were observed between groups, except for pollakiuria (7 vs 22%, p = 0.0031). Multivariate analyses did not show that the treatment group was a significant risk factor for bladder cancer recurrence. CONCLUSIONS: Postoperative two-time intravesical instillation of THP was not superior to single immediate instillation for preventing recurrence after complete resection of a solitary NMIBC.

The assessment of renal cortex and parenchymal volume using automated CT volumetry for predicting renal function after donor nephrectomy.

BACKGROUND: Contrast-enhanced CT is necessary before donor nephrectomy and is usually combined with a Tc-99m-mercapto-acetyltriglycine (MAG3) scan to check split renal function (SRF). However, all transplant programs do not use MAG3 because of its high cost and exposure to radiation. We examined whether CT volumetry of the kidney can be a new tool for evaluating SRF. METHODS: Sixty-three patients underwent live donor nephrectomy. Patients without a 1.0 mm slice CT or follow-up for <12 months were excluded leaving 34 patients' data being analyzed. SRF was measured by MAG3. Split renal volume (SRV) was calculated automatically using volume analyzer software. The correlation between SRF and SRV was examined. The association between the donor's postoperative estimated glomerular filtration rate (eGFR) and predicted eGFR calculated by MAG3 or CT volumetry was analyzed at 1, 3, and 12 months post nephrectomy. RESULTS: Strong correlations were observed preoperatively in a Bland-Altman plot between SRF measured by MAG3 and either CT cortex or parenchymal volumetry. In addition, eGFR after donation correlated with SRF measured by MAG3 or CT volumetry. The correlation coefficients (R) for eGFR Mag3 split were 0.755, 0.615, and 0.763 at 1, 3 and 12 months, respectively. The corresponding R values for cortex volume split were 0.679, 0.638, and 0.747. Those for parenchymal volume split were 0.806, 0.592, and 0.764. CONCLUSION: Measuring kidney by CT volumetry is a cost-effective alternative to MAG3 for evaluating SRF and predicting postoperative donor renal function. Both cortex and parenchymal volumetry were similarly effective.

The perlecan-interacting growth factor progranulin regulates ubiquitination, sorting, and lysosomal degradation of sortilin.

Despite extensive clinical and experimental studies over the past decades, the pathogenesis and progression to the castration-resistant stage of prostate cancer remains largely unknown. Progranulin, a secreted growth factor, strongly binds the heparin-sulfate proteoglycan perlecan, and counteracts its biological activity. We established that progranulin acts as an autocrine growth factor and promotes prostate cancer cell motility, invasion, and anchorage-independent growth. Progranulin was overexpressed in prostate cancer tissues vis-à-vis non-neoplastic tissues supporting the hypothesis that progranulin may play a key role in prostate cancer progression. However, progranulin's mode of action is not well understood and proteins regulating progranulin signaling have not been identified. Sortilin, a single-pass type I transmembrane protein of the Vps10 family, binds progranulin in neurons and targets progranulin for lysosomal degradation. Significantly, in DU145 and PC3 cells, we detected very low levels of sortilin associated with high levels of progranulin production and enhanced motility. Restoring sortilin expression decreased progranulin levels, inhibited motility and anchorage-independent growth and destabilized Akt. These results demonstrated a critical role for sortilin in regulating progranulin and suggest that sortilin loss may contribute to prostate cancer progression. Here, we provide the novel observation that progranulin downregulated sortilin protein levels independent of transcription. Progranulin induced sortilin ubiquitination, internalization via clathrin-dependent endocytosis and sorting into early endosomes for lysosomal degradation. Collectively, these results constitute a regulatory feed-back mechanism whereby sortilin downregulation ensures sustained progranulin-mediated oncogenesis.