Prospective analysis of hydrogel spacer for patients with prostate cancer undergoing radiotherapy.

OBJECTIVE: To report on the dosimetric benefits and late toxicity outcomes after injection of hydrogel spacer (HS) between the prostate and rectum for patients treated with prostate radiotherapy (RT). PATIENTS AND METHODS: In all, 76 patients with a clinical stage of T1-T3a prostate cancer underwent general anaesthesia for fiducial marker insertion plus injection of the HS into the perirectal space before intensity-modulated RT (IMRT) or volumetric-modulated arc RT (VMAT). HS safety, dosimetric benefits, and the immediate- to long-term effects of gastrointestinal (GI) toxicity were assessed. RESULTS: There were no postoperative complications reported. The mean (range) prostate size was 66.0 (25.0-187.0) mm. Rectal dose volume parameters were observed and the volume of rectum receiving 70 Gy (rV70 ), 75 Gy (rV75 ) and 78 Gy (rV78 ) was 7.8%, 3.6% and 0.4%, respectively. In all, 21% of patients (16/76) developed acute Grade 1 GI toxicities, but all were resolved completely by 3 months after treatment; whilst, 3% of patients (2/76) developed late Grade 1 GI toxicities. No patients had acute or late Grade ≥2 GI toxicities. CONCLUSION: Injection of HS resulted in a reduction of irradiated rectal dose volumes along with minimal GI toxicities, irrespective of prostate size.

Mini PCNL for renal calculi: does size matter?

OBJECTIVE: To evaluate the minimally invasive percutaneous nephrolithotomy (MIP) system for renal calculi. PATIENTS AND METHODS: Consecutive patients undergoing mini-percutaneous nephrolithotomy (mPCNL) procedures with the MIP system were enrolled. Patient position, American Society of Anesthesiologists classification, puncture location, stone clearance, postoperative drainage and complications were recorded, and features unique to MIP were noted. RESULTS: In all, 30 patients underwent 32 mPCNL procedures. The mean stone size was 17 (10.75-21.25) mm and the mean number of stones was 1 (1-2). The median stone clearance rate was 96.5 (95-100)%. The complication rate was 9.3%. No patient required a transfusion. In addition to these outcomes, we noted that the MIP system has many advantages over conventional PCNL (cPCNL). It is easy to learn and can be performed in both supine and prone positions. It is safe for supracostal puncture, provides excellent access to nearly all calyces and upper ureter, has multiple stone treatment options, can be used as an adjunct to cPCNL, and can be performed as a tubeless procedure. CONCLUSION: Our experience with the MIP system has shown several advantages over cPCNL. mPCNL with the MIP system has several features that suggest it should be considered as an alternative or adjunct to cPCNL, ureteroscopy and extracorporeal shockwave lithotripsy.

Stone clearance times with mini-percutaneous nephrolithotomy: Comparison of a 1.5 mm ballistic/ultrasonic mini-probe vs. laser.

INTRODUCTION: A limitation of mini-percutaneous nephrolithotomy (mPCNL) is the narrow working channel of mini-nephroscopes, typically restricting instrumentation to 5 French (F) or smaller. We evaluated the efficacy of the 1.5 mm Swiss LithoClast ® Trilogy (Trilogy) rigid probe and compared the results to consecutive cases performed with a 30 W Holmium:YAG (Ho:YAG) laser. METHODS: A retrospective review of 30 consecutive mPCNL cases using the Trilogy and 30 W Holmium laser was performed. A 12 F MIPS nephroscope with a 16.5 F access sheath and 6.7 F working channel was used for all mPCNL cases. The Trilogy was used with a disposable 1.5 mm × 440 mm probe with dual ultrasonic and ballistic energy. The Ho:YAG laser was used with a 550 micron fibre and a maximum of 30 W. Stone clearance time (SCT) was defined by the total time interval between activation of the lithotripter until insertion of the nephrostomy tube and measured in mm2/minutes. SCT included time for fragment retrieval, equipment adjustments, and rigid and flexible nephroscopy during and after lithotripsy. RESULTS: Eleven cases using a 1.5 mm Trilogy probe and 16 cases using a Ho:YAG laser met final inclusion criteria. Three cases using the Trilogy were excluded from final analysis due to conversion to alternative energy sources - two of those were upsized to standard PCNL and one was converted to laser. Mean stone diameter and density in the final Trilogy cohort was 26.7 mm and 1193 Hounsfield units (HU). Mean diameter and density in the laser cohort was 25.2 mm and 1049 HU. The mean stone area clearance time for Trilogy was 4.7±1.8 mm2/minute vs. 3.4±0.7 mm2/minute with Ho:YAG laser (p=0.21). For hard stones, defined as density >1000 HU, the Trilogy averaged 3.7±1.6 mm2/minutes, while the laser averaged 3.1±1.3 mm2/minutes (p=0.786). For soft stones, defined as <1000 HU, the Trilogy averaged 8.9±1.0 mm2/minutes compared to the Ho:YAG, which averaged 3.6±1.8mm2/minutes (p=0.019). No device-related complications occurred in either cohort. CONCLUSIONS: The 1.5 mm mPCNL Trilogy probe was comparable to 30 W Ho:YAG laser for clearing hard stones. The Trilogy performed better than laser on soft stones with a HU density <1000 HU.

Long-term outcomes of external sphincterotomy in a spinal injured population.

PURPOSE: External sphincterotomy is an accepted option for treating patients with detrusor-sphincter dyssynergia. However, long-term outcome data are limited. We ascertained the outcome of treatment results for this procedure. MATERIALS AND METHODS: A database was reviewed for patients undergoing external sphincterotomy at a large tertiary referral spinal injuries center. RESULTS: For 84 primary sphincterotomies the mean duration of successful outcome was 81 months. A second procedure was required in 30 patients and mean duration of success thereafter was 80 months. Recurrent symptomatic episodes of urinary tract infection, recurrent detrusor-sphincter dyssynergia or upper tract dilatation eventually ensued in 57 of 84 patients (68%). Renal failure did not develop in any patients. CONCLUSIONS: External sphincterotomy protects the upper renal tracts and provides extended periods of satisfactory bladder emptying. However, it may require ongoing revision and should potentially be regarded as a staged intervention.

High dose rate brachytherapy boost for prostate cancer: Biochemical control and the impact of transurethral resection of the prostate and hydrogel spacer insertion on toxicity outcomes.

INTRODUCTION: To examine the long-term outcomes of high dose rate brachytherapy boost (HDR-BT) combined with external beam radiotherapy (EBRT) for intermediate and high-risk prostate cancer patients. METHODS: Data from 95 patients who underwent combined EBRT (50.4 Gy) and HDR-BT to the prostate between 2010 and 2017 were retrospectively analysed. Biochemical progression free survival (bPFS), local recurrence free survival (LRFS), metastatic free survival (MFS) and overall survival (OS) were estimated using Kaplan-Meier method. Regression analysis was conducted to identify important predictors of outcomes. RESULTS: A total of 24 patients received an initial HDR-BT dose of 18 Gy in three fractions, with the remaining 71 patients receiving 16 Gy in two fractions as per departmental protocol changes. Most patients (88%) received androgen deprivation therapy. A transurethral resection of the prostate (TURP) was performed in 14 patients and hydrogel spacers (HS) were used in 30 patients. Median follow-up was 58 months. The 5-year bPFS, LRFS, MFS and OS were 92%, 100%, 92% and 88%. Univariate regression revealed no statistical association between patient characteristics and time to relapse (all P > 0.1). Late > grade 2 genitourinary (GU) toxicity was 6.3%. The use of HS or prior TURP had no impact on late GU toxicity. Late Grade 1 gastrointestinal (GI) toxicity was 5.3%. CONCLUSION: The combined HDR-BT with EBRT resulted in excellent bPFS. The cumulative risk of late GU and GI toxicity was low and can be further improved with preventative strategies such as a pre-emptive TURP and/or HS insertion.

Conducting Multiple Imaging Modes with One Fluorescence Microscope.

Fluorescence microscopy is a powerful tool to detect biological molecules in situ and monitor their dynamics and interactions in real-time. In addition to conventional epi-fluorescence microscopy, various imaging techniques have been developed to achieve specific experimental goals. Some of the widely used techniques include single-molecule fluorescence resonance energy transfer (smFRET), which can report conformational changes and molecular interactions with angstrom resolution, and single-molecule detection-based super-resolution (SR) imaging, which can enhance the spatial resolution approximately ten to twentyfold compared to diffraction-limited microscopy. Here we present a customer-designed integrated system, which merges multiple imaging methods in one microscope, including conventional epi-fluorescent imaging, single-molecule detection-based SR imaging, and multi-color single-molecule detection, including smFRET imaging. Different imaging methods can be achieved easily and reproducibly by switching optical elements. This set-up is easy to adopt by any research laboratory in biological sciences with a need for routine and diverse imaging experiments at a reduced cost and space relative to building separate microscopes for individual purposes.

A single institution analysis of low-dose-rate brachytherapy: 5-year reported survival and late toxicity outcomes.

PURPOSE: To report the 5-year biochemical relapse-free survival (BRFS), overall survival (OS), and long-term toxicity outcomes of patients treated with low-dose-rate (LDR) brachytherapy as monotherapy for low- to intermediate-risk prostate cancer. MATERIAL AND METHODS: Between 2004 and 2011, 371 patients were treated with LDR brachytherapy as monotherapy. Of these, 102 patients (27%) underwent transurethral resection of the prostate (TURP) prior to implantation. Follow-up was performed every 3 months for 12 months, then every 6 months over 4 years and included prostate specific antigen evaluation. The biochemical relapse-free survival (BRFS) was defined according to the Phoenix criteria. Acute and late toxicities were documented using the Common Terminology Criteria for Adverse Events version 4.0. The BRFS and OS estimates were calculated using Kaplan-Meier plots. Univariate and multivariate analyses were performed to evaluate outcomes by pre-treatment clinical prognostic factors and radiation dosimetry. RESULTS: The median follow-up of all patients was 5.45 years. The 5-year BRFS and OS rates were 95% and 96%, respectively. The BRFS rates for patients with Gleason score (GS) > 7 and GS ≤ 6 were 96% and 91% respectively (p = 0.06). On univariate analysis, T1 and T2 staging, risk-group classification, and prostate volumes had no impact on survival at 5 years (p > 0.1). Late grade 2 and 3 genitourinary (GU) toxicities were observed in 10% and 5% of patients respectively. Additionally, patients with prior TURP had a greater incidence of late grade 2 or 3 urinary retention (p = 0.001). There were 14 deaths in total; however, none were attributed to prostate cancer. CONCLUSIONS: LDR brachytherapy is an effective treatment option in low- to intermediate-risk prostate cancer patients. We observed low biochemical relapse rates and minimal GU toxicities several years after treatment in patients with or without TURP. However, a small risk of urinary retention was observed in some patients.

Intravesical fat entrapment as a cause of failure of extraperitoneal bladder perforation to heal spontaneously.

We report a case of intravesical fat entrapment leading to failure of extraperitoneal bladder perforation to heal spontaneously. A 68-year-old woman underwent trans-abdominal hysterectomy complicated by an extraperitoneal bladder perforation. Despite prolonged catheterization, cystographic leakage persisted after 3 months. Bladder imaging and cystoscopy demonstrated a mass of perivesical pelvic fat protruding into the bladder cavity. The patient was symptomatic with pain and persistent urinary tract infection with episodes of sepsis. A transurethral resection of the mass was performed which led to bladder healing and resolution of symptoms.

Fixed drug eruption of the penis secondary to sulfamethoxazole-trimethoprim.

Penile lesions are encountered in a variety of fields from family medicine practice through urology, to sexual health specialists. It is important that practitioners consider and recognize fixed drug eruptions of the penis while being able to initiate appropriate treatment in order to avoid misdiagnosis and avoidable stress. In summary, withdrawal of the offending medication and initiation of corticosteroid therapy remain the cornerstones of treatment of fixed drug eruptions of the penis.

A Whole of Population, Multiuser Series of High-Intensity Focused Ultrasound for Management of Localized Prostate Cancer: Outcomes and Implications.

PURPOSE: To determine the oncologic and complication outcomes of treatment of patients with localized prostate cancer by high intensity focused ultrasound (HIFU) for primary management of prostate cancer in a whole of population, multiuser series. PATIENTS AND METHODS: We created a centralized database-accessible only by nonurologist researchers-within a cancer epidemiology center, after ethics approval from that institution. A single researcher prospectively entered baseline, treatment, and clinical/biochemical follow-up data from all patients treated with HIFU in the state of Victoria over the study period. RESULTS: We accrued 108 patients, of whom 103 had been staged as having clinically localized disease. Ninety-three patients (86.1%) had low- or intermediate-risk prostate cancer. Forty-four patients (40.5%) had persistent mild urinary incontinence at 3 months after treatment, and 3 of these ultimately underwent further surgical procedures to correct incontinence. Twenty-seven patients (25%) additionally experienced occasions of urinary retention in the first 3 months after treatment because of passage of tissue. Twenty-nine patients had achieved a prostate-specific antigen level of <0.2 ng/mL at 3 months after HIFU. Fifty-six patients underwent post-HIFU prostate biopsy, and this was positive for residual cancer in 51 cases. Forty-five of the patients who had a positive post-HIFU biopsy underwent secondary treatment for prostate cancer. CONCLUSION: Oncologic control and complication outcomes in this cohort were inferior to those previously reported for HIFU in single-user series. Given the population-based multiuser nature of our series, we believe our observations are more likely to reflect the community outcomes that might be expected from widespread adoption of HIFU than generalizing from single-operator series.

Endoscopic data acquisition and storage.

Recent developments in the field of digital image acquisition and storage provide new opportunities for recording endoscopic procedures for use in the medical record and remote access for education and consultation. This article reviews the recent literature in the field of endoscopy.

Treatment of lower ureteral stones using the Dornier Compact Delta lithotripter.

BACKGROUND AND PURPOSE: Lithotripsy using new-generation machines requires minimal anesthesia and so can easily be given in an outpatient setting. We report our experience with the Dornier Compact Delta lithotripter in the primary management of lower ureteral stones. PATIENTS AND METHODS: We identified 128 patients treated with SWL for lower-ureteral stones between April 1999 and August 2001. Complete follow-up was available for 112 patients. Their ages ranged from 19 to 78 years, with women accounting for 23%. Only three patients had a ureteral stent in situ. All patients were routinely followed up at 2 weeks with a plain film. The timing of further follow-up depended on the initial response to treatment. RESULTS: Fragmentation occurred in 83 of 112 stones (74%): 93% of the successful cases and 43% of the unsuccessful ones. A total of 59 patients (53%) were stone free after one treatment. This figure increased to 73 (65%) after a second treatment. The mean size of the successfully treated stones was less than that of the failed stones (7.6 v 8.7 mm), although the difference did not reach statistical significance. Stone-free rates decreased as stone size increased, being 71% for the 28 stones < or =5 mm in diameter, 65% for the 52 stones 6 to 9 mm, 64% for the 25 stones 10 to 14 mm, and 42% for the 7 stones > or =15 mm. CONCLUSIONS: When SWL can be delivered promptly in an outpatient setting, it remains a useful first-line treatment for lower ureteral stones. Although it is not as effective as ureteroscopy, its use can avert the need for more invasive treatment in half to two thirds of patients. It should be limited to stones <15 mm.

Genetic "lnc"-age of noncoding RNAs to human disease.

The list of functions of long noncoding RNAs (lncRNAs) in human tissues is rapidly growing. To further underscore their critical role in human health, two reports in this issue of JCI associate altered expression of novel lncRNAs with the heritable syndromes HELLP and brachydactyly type E.

Coordination of satellite cell activation and self-renewal by Par-complex-dependent asymmetric activation of p38α/ß MAPK.

In response to muscle injury, satellite cells activate the p38α/ß MAPK pathway to exit quiescence, then proliferate, repair skeletal muscle, and self-renew, replenishing the quiescent satellite cell pool. Although satellite cells are capable of asymmetric division, the mechanisms regulating satellite cell self-renewal are not understood. We found that satellite cells, once activated, enter the cell cycle and a subset undergoes asymmetric division, renewing the satellite cell pool. Asymmetric localization of the Par complex activates p38α/ß MAPK in only one daughter cell, inducing MyoD, which permits cell cycle entry and generates a proliferating myoblast. The absence of p38α/ß MAPK signaling in the other daughter cell prevents MyoD induction, renewing the quiescent satellite cell. Thus, satellite cells employ a mechanism to generate distinct daughter cells, coupling the Par complex and p38α/ß MAPK signaling to link the response to muscle injury with satellite cell self-renewal.

Syndecan-4-expressing muscle progenitor cells in the SP engraft as satellite cells during muscle regeneration.

Skeletal muscle satellite cells, located between the basal lamina and plasma membrane of myofibers, are required for skeletal muscle regeneration. The capacity of satellite cells as well as other cell lineages including mesoangioblasts, mesenchymal stem cells, and side population (SP) cells to contribute to muscle regeneration has complicated the identification of a satellite stem cell. We have characterized a rare subset of the muscle SP that efficiently engrafts into the host satellite cell niche when transplanted into regenerating muscle, providing 75% of the satellite cell population and 30% of the myonuclear population, respectively. These cells are found in the satellite cell position, adhere to isolated myofibers, and spontaneously undergo myogenesis in culture. We propose that this subset of SP cells (satellite-SP cells), characterized by ABCG2, Syndecan-4, and Pax7 expression, constitutes a self-renewing muscle stem cell capable of generating both satellite cells and their myonuclear progeny in vivo.

Functional analysis of the RING-type ubiquitin ligase family of Arabidopsis.

Approximately 5% of the Arabidopsis (Arabidopsis thaliana) proteome is predicted to be involved in the ubiquitination/26S proteasome pathway. The majority of these predicted proteins have identity to conserved domains found in E3 ligases, of which there are multiple types. The RING-type E3 is characterized by the presence of a cysteine-rich domain that coordinates two zinc atoms. Database searches followed by extensive manual curation identified 469 predicted Arabidopsis RING domain-containing proteins. In addition to the two canonical RING types (C3H2C3 or C3HC4), additional types of modified RING domains, named RING-v, RING-D, RING-S/T, RING-G, and RING-C2, were identified. The modified RINGs differ in either the spacing between metal ligands or have substitutions at one or more of the metal ligand positions. The majority of the canonical and modified RING domain-containing proteins analyzed were active in in vitro ubiquitination assays, catalyzing polyubiquitination with the E2 AtUBC8. To help identity regions of the proteins that may interact with substrates, domain analyses of the amino acids outside the RING domain classified RING proteins into 30 different groups. Several characterized protein-protein interaction domains were identified, as well as additional conserved domains not described previously. The two largest classes of RING proteins contain either no identifiable domain or a transmembrane domain. The presence of such a large and diverse number of RING domain-containing proteins that function as ubiquitin E3 ligases suggests that target-specific proteolysis by these E3 ligases is a complex and important part of cellular regulation in Arabidopsis.