Initial transperineal prostate biopsy experience at a high-volume center.

INTRODUCTION: Transperineal prostate biopsy (TPBx) allows for prostate cancer detection with fewer infectious complications when compared to transrectal prostate biopsy (TRUSBx). We evaluated the initial experience of a single physician with no prior TPBx exposure, compared to TRUSBx and MRI/US fusion biopsy (MRIBx) performed by experienced physicians. MATERIALS AND METHODS: All consecutive patients undergoing prostate biopsy (June 2019-March 2020) were included. Patient discomfort, procedural time, clinically significant cancer detection rates (csCDR) and 30-day complications were compared between TPBx, TRUSBx and MRIBx. RESULTS: A total of 303 patients underwent biopsy. Comparing TPBx to TRUSBx to MRIBx, median pain scores during the anesthetic block were 4 versus 2 versus 3 (p = 0.007) respectively, and not statistically different during the rest of the procedure. Median time of biopsy was 11, 7.5 and 12 minutes respectively. csCDR were 38%, 29.8%, and 43.6% (p = 0.12) respectively. The combined transrectal groups (n = 211) had nine complications including two sepsis events. The TPBx group (n = 92) had no 30-day complications. CONCLUSIONS: TPBx was well tolerated in the office setting with similar levels of discomfort for all aspects of the procedure compared to transrectal approach. Learning curve for TPBx showed rapid improvement in procedural time within the first 15 cases with an average procedure time of 9 minutes thereafter. Similar rates of csCDR were found between the groups and TPBx had significantly fewer infectious complications than standard transrectal technique.

A window-of-opportunity clinical trial of dasatinib in women with newly diagnosed endometrial cancer.

OBJECTIVE: To determine the extent of dasatinib uptake and effect on Src kinase activity in tumor, normal adjacent tissue, and blood in newly diagnosed endometrial cancer patients. METHODS: Dasatinib was dosed at 100 or 200 mg PO BID at 32 and 8 h preoperatively. Blood and tissue were collected pre-treatment and at surgery to assess active (pY419) and total Src protein (pharmacodynamics [PD]) and pharmacokinetics (PK). Plasma PK and PD were also analyzed at 2, 4 and 8 h following the second dose. RESULTS: Ten patients completed the study, 5 at each dose level (DL). Average (median, standard deviation, range) 2 h plasma concentration of drug was 119 (121, 80, 226) and 236 (162, 248, 633) ng/mL, for the 100 and 200 mg DL, respectively. Average ratio of 8 h normal and tumor tissue to plasma concentration overall was 3.6 (2.3, 3.4, 9.6) and 8.3 (3.2, 11.9, 38.7), respectively. Dasatinib concentration in tumor was higher than in plasma for both DL. Four patients displayed significant reductions in pTyr419Src at ≥ 1 time points in blood, and four patients satisfied the PD activity criteria in tissue, with reductions in pTyr419Src of ≥ 60%. CONCLUSIONS: This is the first study to show PK and PD effects of dasatinib in tumor tissue, allowing evaluation of tissue PD markers as a function of tumor dasatinib concentration. Dasatinib tissue concentrations at 8 h after dosing were associated with modulation of pTyr419Src, total Src protein, and pTyr419Src/Src ratio. All patients had reduction in at least one Src parameter in either tissue or blood.

Epidermal growth factor receptor translocation to the mitochondria: regulation and effect.

Co-overexpression of the epidermal growth factor (EGF) receptor (EGFR) and c-Src frequently occurs in human tumors and is linked to enhanced tumor growth. In experimental systems this synergistic growth requires EGF-dependent association of c-Src with the EGFR and phosphorylation of Tyr-845 of the receptor by c-Src. A search for signaling mediators of Tyr(P)-845 revealed that mitochondrial cytochrome c oxidase subunit II (CoxII) binds EGFR in a Tyr(P)-845- and EGF-dependent manner. In cells this association involves translocation of EGFR to the mitochondria, but regulation of this process is ill-defined. The current study demonstrates that c-Src translocates to the mitochondria with similar kinetics as EGFR and that the catalytic activity of EGFR and c-Src as well as endocytosis and a mitochondrial localization signal are required for these events. CoxII can be phosphorylated by EGFR and c-Src, and EGF stimulation reduces Cox activity and cellular ATP, an event that is dependent in large part on EGFR localized to the mitochondria. These findings suggest EGFR plays a novel role in modulating mitochondrial function via its association with, and modification of CoxII.

Incidence of post-pyelonephritic renal scarring: a meta-analysis of the dimercapto-succinic acid literature.

PURPOSE: We investigated ethnic differences in the risk of post-pyelonephritic renal scarring in infants and children for possible genetic determinants. MATERIALS AND METHODS: We searched all peer reviewed articles published from 1980 through 2006 in the PubMed(R), MEDLINE(R) (Ovid), Cochrane Central Register of Controlled Trials and EMBASE(R) databases for the keywords, "renal scarring and pyelonephritis," "renal fibrosis" and "kidney scarring." References were included only when they specified acute pyelonephritis defined by a fever, positive urine culture and areas of photopenia in the renal cortex on 99mtechnetium dimercapto-succinic acid renal scans, repeat dimercapto-succinic acid scans obtained at least 3 months after acute pyelonephritis to assess for renal cortical scar formation and absence of recurrent urinary tract infection during followup. When possible data were analyzed according to patients and renal units. RESULTS: Among 23 references the overall rates of renal scarring in terms of patients and renal units were 41.6% and 37.0%, respectively. In terms of patients the incidence of renal scarring following acute pyelonephritis varied by region, from 26.5% (Australia) to 49.0% (Asia). In terms of renal units the incidence of acquired renal cortical scarring varied by region, from 16.7% (Middle East) to 58.4% (Asia). When combined by vesicoureteral reflux status children and renal units with refluxing ureters exhibited an increased risk of renal scarring (odds ratios 2.8 and 3.7, respectively). CONCLUSIONS: Although scarring was different across some regions, only scarring in Asian studies comparing patients displayed a statistically significant difference. A regional effect explained the heterogeneity observed in the overall estimate for patients and partly for renal units. The greatest risk of renal scarring may be imparted by the presence of vesicoureteral reflux.

Role of prophylaxis in vesicoureteral reflux.

PURPOSE OF REVIEW: Traditional management of vesicoureteral reflux focuses on preventing renal complications associated with ascending urinary tract infection by either providing continuous antibiotic prophylaxis to sterilize the urine and thus prevent recurrent infection, or abolishing reflux via surgical intervention. This review will consider the rationale for antibiotic prophylaxis in light of contemporary data regarding the natural history of vesicoureteral reflux, urinary tract infection and renal scarring, as well as the efficacy of various treatment strategies. RECENT FINDINGS: Recent studies have shown that in grades I-IV vesicoureteral reflux, open surgical intervention compared with antibiotic prophylaxis is no better at preventing renal complications. Endoscopic subureteral injection of biomaterials has been proposed as a cost-effective, minimally invasive alternative to surgical or medical intervention; however, given the variety of materials and techniques, the literature has yet to achieve consensus on its efficacy. The first study to compare antibiotic prophylaxis with increased surveillance and prompt treatment of urinary tract infection shows no difference between the two approaches in low-grade (grades I-II) vesicoureteral reflux. SUMMARY: Recent studies have challenged the traditional paradigm of aggressive vesicoureteral reflux management with surgery or antibiotic prophylaxis. In light of these findings, pediatric urologists will need to reexamine treatment modalities for vesicoureteral reflux.