What proportion of embryos should be considered for transfer following a mosaic diagnosis? A study of 115 clinics from a central diagnostic laboratory.

PURPOSE: The aim of this study is to identify what proportion of mosaic embryo diagnoses should be considered for transfer, and thereby assess the impact on patient cases. METHODS: We categorised mosaic embryos into 3 groups; high, medium and low priority for transfer based on the percentage of biopsy sample being aneuploid and the chromosomes involved. The categories were applied to those patients that had no euploid embryo diagnoses but 1 or more mosaic embryos identified as mosaic available after PGT-A. RESULTS: In total, 6614 PGT-A cases from 115 clinics and a single diagnostic laboratory were reviewed. Further, 1384 [20.9%] cases only had aneuploid embryos, 4538 [68.6%] cases had one or more euploid embryos and 692 [10.5%] cases had no euploid and one or more mosaic embryo. The mosaic embryos in the no euploid, one or more mosaic group, when reviewed using priorities, resulted in: 111 [1.7%] of cases having at least one high priority mosaic available. 184 [2.8%] of cases having no high priority but at least one medium priority mosaic available. 397 [6.0%] of cases only having low priority mosaic embryos available. CONCLUSION: Based on this data, embryos identified as mosaic will only be considered for transfer in the first instance for around 4.5% (when taking high and medium priority and excluding low priority cases) of all PGT-A cases.

Utilization of standardized preimplantation genetic testing for aneuploidy (PGT-A) via artificial intelligence (AI) technology is correlated with improved pregnancy outcomes in single thawed euploid embryo transfer (STEET) cycles.

PURPOSE: To investigate the role of standardized preimplantation genetic testing for aneuploidy (PGT-A) using artificial intelligence (AI) in patients undergoing single thawed euploid embryo transfer (STEET) cycles. METHODS: Retrospective cohort study at a single, large university-based fertility center with patients undergoing in vitro fertilization (IVF) utilizing PGT-A from February 2015 to April 2020. Controls included embryos tested using subjective NGS. The first experimental group included embryos analyzed by NGS utilizing AI and machine learning (PGTaiSM Technology Platform, AI 1.0). The second group included embryos analyzed by AI 1.0 and SNP analysis (PGTai2.0, AI 2.0). Primary outcomes included rates of euploidy, aneuploidy and simple mosaicism. Secondary outcomes included rates of implantation (IR), clinical pregnancy (CPR), biochemical pregnancy (BPR), spontaneous abortion (SABR) and ongoing pregnancy and/or live birth (OP/LBR). RESULTS: A total of 24,908 embryos were analyzed, and classification rates using AI platforms were compared to subjective NGS. Overall, those tested via AI 1.0 showed a significantly increased euploidy rate (36.6% vs. 28.9%), decreased simple mosaicism rate (11.3% vs. 14.0%) and decreased aneuploidy rate (52.1% vs. 57.0%). Overall, those tested via AI 2.0 showed a significantly increased euploidy rate (35.0% vs. 28.9%) and decreased simple mosaicism rate (10.1% vs. 14.0%). Aneuploidy rate was insignificantly decreased when comparing AI 2.0 to NGS (54.8% vs. 57.0%). A total of 1,174 euploid embryos were transferred. The OP/LBR was significantly higher in the AI 2.0 group (70.3% vs. 61.7%). The BPR was significantly lower in the AI 2.0 group (4.6% vs. 11.8%). CONCLUSION: Standardized PGT-A via AI significantly increases euploidy classification rates and OP/LBR, and decreases BPR when compared to standard NGS.

The epidermal growth factor receptor critically regulates endometrial function during early pregnancy.

Infertility and adverse gynecological outcomes such as preeclampsia and miscarriage represent significant female reproductive health concerns. The spatiotemporal expression of growth factors indicates that they play an important role in pregnancy. The goal of this study is to define the role of the ERBB family of growth factor receptors in endometrial function. Using conditional ablation in mice and siRNA in primary human endometrial stromal cells, we identified the epidermal growth factor receptor (Egfr) to be critical for endometrial function during early pregnancy. While ablation of Her2 or Erbb3 led to only a modest reduction in litter size, mice lacking Egfr expression are severely subfertile. Pregnancy demise occurred shortly after blastocyst implantation due to defects in decidualization including decreased proliferation, cell survival, differentiation and target gene expression. To place Egfr in a genetic regulatory hierarchy, transcriptome analyses was used to compare the gene signatures from mice with conditional ablation of Egfr, wingless-related MMTV integration site 4 (Wnt4) or boneless morphogenic protein 2 (Bmp2); revealing that not only are Bmp2 and Wnt4 key downstream effectors of Egfr, but they also regulate distinct physiological functions. In primary human endometrial stromal cells, marker gene expression, a novel high content image-based approach and phosphokinase array analysis were used to demonstrate that EGFR is a critical regulator of human decidualization. Furthermore, inhibition of EGFR signaling intermediaries WNK1 and AKT1S1, members identified in the kinase array and previously unreported to play a role in the endometrium, also attenuate decidualization. These results demonstrate that EGFR plays an integral role in establishing the cellular context necessary for successful pregnancy via the activation of intricate signaling and transcriptional networks, thereby providing valuable insight into potential therapeutic targets.

Activin-like kinase 2 functions in peri-implantation uterine signaling in mice and humans.

Implantation of a blastocyst in the uterus is a multistep process tightly controlled by an intricate regulatory network of interconnected ovarian, uterine, and embryonic factors. Bone morphogenetic protein (BMP) ligands and receptors are expressed in the uterus of pregnant mice, and BMP2 has been shown to be a key regulator of implantation. In this study, we investigated the roles of the BMP type 1 receptor, activin-like kinase 2 (ALK2), during mouse pregnancy by producing mice carrying a conditional ablation of Alk2 in the uterus (Alk2 cKO mice). In the absence of ALK2, embryos demonstrate delayed invasion into the uterine epithelium and stroma, and upon implantation, stromal cells fail to undergo uterine decidualization, resulting in sterility. Mechanistically, microarray analysis revealed that CCAAT/enhancer-binding protein ß (Cebpb) expression is suppressed during decidualization in Alk2 cKO females. These findings and the similar phenotypes of Cebpb cKO and Alk2 cKO mice lead to the hypothesis that BMPs act upstream of CEBPB in the stroma to regulate decidualization. To test this hypothesis, we knocked down ALK2 in human uterine stromal cells (hESC) and discovered that ablation of ALK2 alters hESC decidualization and suppresses CEBPB mRNA and protein levels. Chromatin immunoprecipitation (ChIP) analysis of decidualizing hESC confirmed that BMP signaling proteins, SMAD1/5, directly regulate expression of CEBPB by binding a distinct regulatory sequence in the 3' UTR of this gene; CEBPB, in turn, regulates the expression of progesterone receptor (PGR). Our work clarifies the conserved mechanisms through which BMPs regulate peri-implantation in rodents and primates and, for the first time, uncovers a linear pathway of BMP signaling through ALK2 to regulate CEBPB and, subsequently, PGR during decidualization.

Sex disparities in diagnosis of bladder cancer after initial presentation with hematuria: a nationwide claims-based investigation.

BACKGROUND: Women have disproportionately higher mortality rates relative to incidence for bladder cancer. Multiple etiologies have been proposed, including delayed diagnosis and treatment. Guidelines recommend ruling out malignancy in men and women presenting with hematuria. This study sought to determine the difference in timing from presentation with hematuria to diagnosis of bladder cancer in women versus men. METHODS: This is a retrospective population-based study examining the timing from presentation with hematuria to diagnosis of bladder cancer, based on data from the MarketScan databases, which include enrollees of more than 100 health insurance plans of approximately 40 large US employers from 2004 through 2010. All study patients presented with hematuria and were subsequently diagnosed with bladder cancer. The primary outcome measure was number of days between initial presentation with hematuria and diagnosis of bladder cancer by sex. RESULTS: A total of 5416 men and 2233 women met inclusion criteria. Mean days from initial hematuria claim to bladder cancer claim was significantly longer in women (85.4 versus 73.6 days, P < .001), and the proportion of women with >6 month delay in bladder cancer diagnosis was significantly higher (17.3% versus 14.1%, P < .001). Women were more likely to be diagnosed with urinary tract infection (odds ratio = 2.32, 95% confidence interval = 2.07-2.59) and less likely to undergo abdominal or pelvic imaging (odds ratio = 0.80, 95% confidence interval = 0.71-0.89). CONCLUSIONS: Both men and women experience significant delays between presentation with hematuria and diagnosis of bladder cancer, with longer delays for women. This may be partly responsible for the sex-based discrepancy in outcomes associated with bladder cancer.

Early removal of urethral catheter with suprapubic tube drainage versus urethral catheter drainage alone after robot-assisted laparoscopic radical prostatectomy.

PURPOSE: Retrospective single institution data suggest that postoperative pain after robot-assisted laparoscopic radical prostatectomy is decreased by early removal of the urethral catheter with suprapubic tube drainage. In a randomized patient population we determined whether suprapubic tube drainage with early urethral catheter removal would improve postoperative pain compared with urethral catheter drainage alone. MATERIALS AND METHODS: Men with a body mass index of less than 40 kg/m(2) who had newly diagnosed prostate cancer and elected robot-assisted laparoscopic radical prostatectomy were included in analysis. Block randomization by surgeon was used and randomization assignment was done after completing the urethrovesical anastomosis. In patients assigned to suprapubic tube drainage the urethral catheter was removed on postoperative day 1 and all catheters were removed on postoperative day 7. Visual analog pain scale and satisfaction questionnaires were administered on postoperative days 0, 1 and 7. RESULTS: A total of 29 patients were randomized to the urethral catheter vs 29 to the suprapubic tube plus early urethral catheter removal at the time of interim futility analysis. Mean visual analog pain scale scores did not differ between the groups at any time point and a similar percent of patients cited the catheter as the greatest bother with nonsignificant differences in treatment related satisfaction. Complications during postoperative week 1 did not vary between the groups. Based on interim results the trial was terminated due to lack of effect. CONCLUSIONS: Patients randomized to suprapubic tube vs urethral catheter drainage for the week after prostatectomy had similar pain, catheter related bother and treatment related satisfaction in the perioperative period. We no longer routinely offer suprapubic tube drainage with early urethral catheter removal at our institution.

Cystectomy and urinary diversion as management of treatment-refractory benign disease: the impact of preoperative urological conditions on perioperative outcomes.

OBJECTIVES: To investigate perioperative outcomes associated with cystectomy and urinary diversion for treatment-refractory benign urological disease. METHODS: A cohort of patients who underwent cystectomy for infection, fistula, bleeding, incontinence, neurogenic bladder or pain between January 2004 and June 2012 was established. Data included baseline demographics, indications for cystectomy and prior treatments, and complications at 30 and 90 days. Primary outcome measures were 30-day and 30 to 90-day complications. RESULTS: The study group comprised eight males and 18 females. The mean age was 57.8 years (95% CI 50.8-64.7). A total of 19 patients (73%) had resolution of their underlying urological pathology at 90 days. A total of 19 patients (73%) experienced a complication in the first 30 days, of which nine (47%) were Clavien grade III or higher. The most common 30-day complications were urinary tract infection (n = 6, 23%) and wound infection (n = 6, 23%). A total of 44% (4/9) of patients with neurogenic bladder experienced a complication within the first 30 days of cystectomy compared with 100% (8/8) of patients with radiation-induced fistula (P = 0.03) and 78% (7/9) of non-neurogenic, non-radiation-induced fistula patients (P = 0.34). CONCLUSIONS: Cystectomy with urinary diversion for benign disease might be successful, but is associated with a high rate of perioperative complications. Those with radiation-induced fistula are more likely to experience complications, whereas those with neurogenic bladder carry a lower risk. Patients should be counseled appropriately regarding expected postoperative outcomes.

The impact of running versus interrupted anastomosis on ureterointestinal stricture rate after radical cystectomy.

PURPOSE: Benign ureterointestinal anastomotic stricture is not uncommon after radical cystectomy and urinary diversion. We studied the impact of the running vs the interrupted technique on the ureterointestinal anastomotic stricture rate. MATERIALS AND METHODS: From July 2007 to December 2008 interrupted end-to-side anastomoses were created and from January 2009 to July 2010 running anastomoses were created. The primary study end point was time to ureterointestinal anastomotic stricture. RESULTS: Of 266 consecutive patients 258 were alive 30 days after radical cystectomy, including 149 and 109 with an interrupted and a running anastomosis, respectively. The groups did not differ in age, gender, body mass index, age adjusted Charlson comorbidity index, receipt of chemotherapy or radiation, blood loss, operative time, diversion type or postoperative pathological findings. The stricture rate per ureter was 8.5% (25 of 293) and 12.7% (27 of 213) in the interrupted and running groups, respectively (p = 0.14). Univariate analysis suggested that postoperative urinary tract infection (HR 2.1, 95% CI 1.1-4.1, p = 0.04) and Clavien grade 3 or greater complications (HR 2.6, 95% CI 1.4-4.9, p <0.01) were associated with ureterointestinal anastomotic stricture. On multivariate analysis postoperative urinary tract infection (HR 2.4, 95% CI 1.2-5.1, p = 0.02) and running technique (HR 1.9, 95% CI 1.0-3.7, p = 0.05) were associated with ureterointestinal anastomotic stricture. Median time to stricture and followup was 289 (IQR 120-352) and 351 days (IQR 132-719) in the running cohort vs 213 (IQR 123-417) and 497 days (IQR 174-1,289) in the interrupted cohort, respectively. Of the 52 strictures 33 (63%) developed within 1 year. Kaplan-Meier analysis controlling for differential followup showed a trend toward higher freedom from stricture for the interrupted ureterointestinal anastomosis (p = 0.06). CONCLUSIONS: A running anastomosis and postoperative urinary tract infection may be associated with ureterointestinal anastomotic stricture. Larger series with multiple surgeons are needed to confirm these findings.

Epithelial progesterone receptor exhibits pleiotropic roles in uterine development and function.

The ovarian steroid progesterone, acting through the progesterone receptor (PR), coordinates endometrial epithelial-stromal cell communication, which is critical for its development and function. PR expression in these cellular compartments is under tight temporal and endocrine control. Although ex vivo studies demonstrated the importance of stromal PR expression, they failed to show a role for epithelial PR in uterine function. Here, the in vivo role of PR in the uterine epithelium is defined using floxed PR (PR(f/f)) mice crossed to Wnt7a-Cre mice. Progesterone was unable to stimulate the expression of its epithelial target genes, including Ihh, in the Wnt7a-Cre(+)PR(f/-) mice. Analysis was conducted on Ihh to determine whether PR directly regulates epithelial gene transcription. ChIP-on-chip analysis identified PR binding sites in the 5'-flanking region of Ihh. Cotransfection of the proximal Ihh promoter with PR demonstrated that PR directly regulates Ihh transcription. Female Wnt7a-Cre(+)PR(f/-) mice are infertile due to defects in embryo attachment, stromal cell decidualization, and the inability to cease estrogen-induced epithelial cell proliferation. Finally, progesterone was unable to inhibit neonatal endometrial glandular development in Wnt7a-Cre(+)PR(f/-) mice. Thus, epithelial PR is necessary for the regulation of progesterone epithelial target gene expression, as well as uterine function and development.

Empiric antibiotics for an elevated prostate-specific antigen (PSA) level: a randomised, prospective, controlled multi-institutional trial.

OBJECTIVE: To determine the impact of empiric antibiotics on men with an elevated prostate-specific antigen (PSA) level. SUBJECTS/PATIENTS AND METHODS: Men of any age with a PSA level of >2.5 ng/mL and normal digital rectal examination undergoing their first prostate biopsy were recruited from five medical centres. Patients with previous biopsy, prostate cancer, urinary tract infection (UTI) or prostatitis within the prior year, antibiotic use within 1 month, 5α-reductase inhibitor use, allergy to fluoroquinolones or clinical suspicion of UTI were excluded. Men were randomised to 2 weeks of ciprofloxacin or no antibiotic. A PSA measurement was obtained 21-45 days after randomisation immediately before prostate biopsy. The primary endpoint was the change in PSA level between baseline and immediately before biopsy. RESULTS: Complete data were available for 77 men with a mean (interquartile range) age of 60.6 (53-66) years. In the control group of men not receiving antibiotic (39 men), the mean baseline and pre-biopsy PSA levels were 6.5 and 6.9 ng/mL, respectively (P = 0.8). In men receiving ciprofloxacin (38 men), the mean baseline PSA level was 7.6 ng/mL and after 2 weeks of ciprofloxacin was 8.5 ng/mL (P = 0.7). Compared with controls not receiving antibiotic, use of ciprofloxacin was not associated with a statistically significant change in PSA level (P = 0.33). Prostate cancer was detected in 36 (47%) men, 23 (59%) in the control group and 13 (34%) in the antibiotic group (P = 0.04). Detection rates were not significantly associated with the change in PSA level between baseline and biopsy. The primary limitation of the study is early stoppage due to an interim futility analysis and poor accrual. CONCLUSION: Despite not meeting the target accrual goal, empiric use of antibiotics for asymptomatic men with an elevated PSA level does not appear to be of clinical benefit.

Biodynamic prediction of neoadjuvant chemotherapy response: Results from a prospective multicenter study of predictive accuracy among muscle-invasive bladder cancer patients.

BACKGROUND: Biodynamic signatures (temporal patterns of microscopic motion within a 3-dimensional tumor explant) offer phenomic biomarkers that are highly predictive for therapeutic response. OBJECTIVE: By utilizing motility contrast tomography, which provides a simple, fast assessment of motion patterns in living tissue, we evaluated the predictive accuracy of a biodynamic drug response classifier in muscle-invasive bladder cancer (MIBC) patients undergoing neoadjuvant chemotherapy (NAC). DESIGN, SETTING, AND PARTICIPANTS: One hundred five consecutive bladder cancer patients suspected of having MIBC were screened in a multi-institutional prospective observational study (NCT03739177) from July 2018 to June 2020, of whom, 30 completed NAC and radical cystectomy. INTERVENTION(S): Biodynamic signatures from treatment-naïve fresh bladder tumor specimens obtained after transurethral resection were measured in living tumor fragments challenged by standard-of-care cytotoxins. Patients received gemcitabine and cisplatin or dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin per institutional guidelines and were followed through radical cystectomy. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: A 4-level classifier was developed to predict pathologic complete response (pCR) vs. incomplete response utilizing a one-left-out cross-validation protocol to minimize over-fitting. Area under the curve evaluated predictive utility. RESULTS: Thirty percent (9 of 30) achieved pCR. Utilizing the 4-level classifier, biodynamically "favored" (scoring ≥ 3) and "strongly favored" (scoring 4) regimens accurately predicted pCR at rates of 66.7% (4 of 6 patients) and 100% (4 of 4 patients), respectively. Biodynamically "favored" scores predicted pCR with 88% sensitivity and 95% negative predictive value, P < 0.0001. Only 5.0% (1 of 20 patients) achieved pCR from regimens scoring 1 or 2, indicating poor to no response from NAC. Area under the receiver operating curve was 96% (95% Confidence Interval: 79%-99%, P < 0.0001). Future direction involves validating this model prospectively. PRINCIPAL CONCLUSIONS: Biodynamic scoring accurately predicts response in MIBC patients receiving NAC and holds promise to substantially improve the scope of appropriate management intervention.

The impact of mechanical bowel preparation on postoperative complications for patients undergoing cystectomy and urinary diversion.

PURPOSE: The benefit of routine mechanical bowel preparation for patients undergoing radical cystectomy is not well established. We compared postoperative complications in patients who did or did not undergo mechanical bowel preparation before radical cystectomy. MATERIALS AND METHODS: In 2008 a single surgeon (GDS) performed open radical cystectomy with an ileal conduit or orthotopic neobladder in 105 consecutive patients with preoperative mechanical bowel preparation consisting of 4 l GoLYTELY®. In 2009 radical cystectomy with an ileal conduit or orthotopic neobladder was performed in 75 consecutive patients without mechanical bowel preparation. A comprehensive database provided clinical, pathological and outcome data. RESULTS: All patients had complete perioperative data available. The 2 groups were similar in age, Charlson comorbidity score, diversion type, receipt of neoadjuvant radiation or chemotherapy, blood loss, hospital stay, time to diet and pathological stage. Postoperative urinary tract infection, wound dehiscence and perioperative death rates were similar in the 2 groups. Clostridium difficile infection developed within 30 days of surgery in 11 of 105 vs 2 of 75 patients with vs without mechanical bowel preparation (p = 0.08). When adjusted for the annual hospital-wide C. difficile rate, the difference remained insignificant (p = 0.21). Clavien grade 3 or greater abdominal and gastrointestinal complications, including fascial dehiscence, abdominal abscess, small bowel obstruction, bowel leak and entero-diversion fistula, developed in 7 of 105 patients with (6.7%) vs 11 of 75 without (14.7%) mechanical bowel preparation (p = 0.08). CONCLUSIONS: The use of mechanical bowel preparation for patients undergoing radical cystectomy with an ileal conduit or orthotopic neobladder does not seem to impact the rates of perioperative infectious, wound and bowel complications. Larger series with multiple surgeons are necessary to confirm these findings.

Robotic paediatric urology.

UNLABELLED: What's known on the subject? and What does the study add? Robot assisted laparoscopic surgery (RALS) is slowly gaining acceptance in the field of paediatric urology. Accumulating data on safety and efficacy when performing paediatric robotic urologic procedures has led paediatric urologists to gradually embrace increasingly more complex reconstructive surgeries. Indeed, the unique and delicate movements generated by the robotic system make this technology ideal for children who often require reconstructive procedures. We critically review the current role of RALS in paediatric urology and to analyse the published data, with a special emphasis on the most common applications. We also propose a structured plan to expedite training and the surgical 'learning curve'. OBJECTIVES: To critically review the current role of robot-assisted laparoscopic surgery (RALS) in paediatric urology and to analyse the published data, with a special emphasis on the most common applications. One of the greatest benefits of RALS has been the ability to truly spread the application of minimally invasive surgery to paediatric surgical patients. The unique attributes of the robotic interface make this technology ideal for children with congenital anomalies, who often require reconstructive procedures. We also propose a structured plan to expedite training and the surgical 'learning curve'. PATIENTS AND METHODS: Currently, almost all urological surgical procedures in children have been performed with the assistance of the robotic interface. The most commonly performed procedures include pyeloplasty, nephrectomy/hemi-nephrectomy and surgery for vesico-ureteric reflux. Initial series of bladder augmentation and appendicovesicostomy are available. RESULTS: Initial results with RALS are encouraging and have shown safety similar to open procedures, and outcomes at least equivalent to standard laparoscopy. Accumulating data have consistently shown that postoperative analgesia requirements and overall hospital stay are decreased. However, operative durations are significantly longer than their open counterparts, but this is decreasing as experience accumulates. CONCLUSIONS: RALS is already part of paediatric urological surgery. Larger single-institution case series and comparative studies with the open approach and multi-institutional meta-analyses will help to identify the benefits of RALS in paediatric urology.

Foxa2 is essential for mouse endometrial gland development and fertility.

During embryonic development, Foxa2 is required for the formation of the node and notochord, and ablation of this gene results in defects in gastrulation, neural tube patterning, and gut morphogenesis. Foxa2 has been shown to be expressed specifically in the glandular epithelium of the murine uterus. To study the uterine function of Foxa2, this gene was conditionally ablated in the mouse uterus by crossing mice with floxed Foxa2 alleles, Foxa2(loxP/loxP), with the Pgr(cre) mouse model. Pgr(cre/+) Foxa2(loxP/loxP) mice showed significantly reduced fertility. Analysis of the uterus on Day 5.5 of pregnancy showed disrupted blastocyst implantation. Pgr(cre/+) Foxa2(loxP/loxP) mice also showed a severe impairment of the uterus to respond to the artificial induction of the decidual response. Morphological examination of the uteri of these mice showed a severe reduction in the number of endometrial glands. The loss of endometrial glands resulted in the reduction of leukemia inhibitory factor (Lif) expression. The lack of a decidual response could be partially rescued by an intrauterine injection of LIF before the initiation of the decidual response. This analysis demonstrates that Foxa2 regulates endometrial gland development and that mice with a loss of endometrial glands cannot support implantation in part due to the loss of LIF, which is a requisite for fertility in the mouse.

Orthotopic neobladder versus Indiana pouch in women: a comparison of health related quality of life outcomes.

PURPOSE: Little is known about the health related quality of life of women who have undergone continent urinary diversion. We compared health related quality of life outcomes for women who underwent radical cystectomy with an orthotopic neobladder or Indiana pouch. MATERIALS AND METHODS: From 1995 to June 2008 a single surgeon (GDS) performed radical cystectomy with an orthotopic neobladder in 47 women and radical cystectomy with an Indiana pouch in 45. A comprehensive database provided clinical, pathological and outcomes data. The validated Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index was mailed to 92 patients. RESULTS: Complete data were available for 87% of patients treated with radical cystectomy with an orthotopic neobladder and 93% of those treated with radical cystectomy with an Indiana pouch, with a median followup of 34 and 24 months, respectively (p = 0.8). Median (IQR) age was 65 (58, 71) and 61.5 (51, 67) years for patients with an orthotopic neobladder and Indiana pouch, respectively (p = 0.03). No significant differences were found for pathological stage, nodal status, blood loss, Clavien grade III or greater complications, adjuvant therapy or hospital stay between the 2 treatment groups, or between respondents and nonrespondents. Five-year survival rates for patients with an orthotopic neobladder and Indiana pouch were 65% and 58%, respectively (p = 0.9). There were 21 (75%) living patients with an orthotopic neobladder and 19 (61%) with an Indiana pouch who completed the Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index, and physical (p = 0.53), social (p = 0.97), emotional (p = 0.61), functional (p = 0.55) and radical cystectomy specific (p = 0.54) health related quality of life domains were not significantly different between the groups. CONCLUSIONS: Women undergoing radical cystectomy with an orthotopic neobladder vs an Indiana pouch have similar health related quality of life outcomes. Larger series with longer followup and multiple surgeons are necessary to confirm these findings.

The prevalence of pathologic skin picking in US adults.

OBJECTIVE: Despite increasing recognition of the potentially severe medical and psychosocial costs of pathologic skin picking (PSP), no large-sample, randomized investigation of its prevalence in a national population has been conducted. METHOD: Two thousand five hundred and thirteen US adults were interviewed during the spring and summer of 2004 in a random-sample, national household computer-assisted phone survey of PSP phenomenology and associated functional impairment. Respondents were classified for subsequent analysis according to proposed diagnostic criteria. RESULTS: Of all respondents, 16.6% endorsed lifetime PSP with noticeable skin damage; 60.3% of these denied picking secondary to an inflammation or itch from a medical condition. One fifth to one quarter of those with lifetime PSP not related to a medical condition endorsed tension or nervousness before picking, tension or nervousness when attempting to resist picking, and pleasure or relief during or after picking. A total of 1.4% of our entire sample satisfied our criteria of picking with noticeable skin damage not attributable to another condition and with associated distress or psychosocial impairment. Pickers satisfying these latter criteria differed from other respondents in demographics (age, marital status) and both picking phenomenology and frequency.

Retroperitoneal lymph node dissection: reassessment of modified templates.

The retroperitoneum is the initial metastatic site in 90% of patients with nonseminomatous germ cell tumours (NSGCTs) of the testis. A retroperitoneal lymph node dissection (RPLND) provides accurate staging and effective therapy, minimizes the need for adjuvant chemotherapy in patients with low-volume metastases, and optimizes durable cure rates. We review the rationale for and development of RPLND, focusing specifically on the advantages and limitations of the variable surgical templates. Bilateral RPLND has a long-standing record of maximizing cancer control and minimizing secondary therapy. Both modified templates and prospective nerve-sparing techniques were introduced to optimize rates of antegrade ejaculation. Limited resections as advocated by modified templates are appealing in the setting of primary RPLND but can be associated with a 3-23% risk of residual disease. Modified templates have also been advocated for highly selected patients after chemotherapy but, if applied to all patients undergoing surgery after chemotherapy, will lead to an unacceptably high rate of residual disease, even in patients with small masses after chemotherapy. For patients undergoing primary or post-chemotherapy RPLND, a full bilateral template (with nerve-sparing when appropriate) maximizes cure rates while minimizing ejaculatory morbidity and the subsequent need for chemotherapy.

Active surveillance for low-risk localized prostate cancer.

The management of localized prostate cancer in an otherwise healthy male is complex, evolving, and largely consists of three modalities: surgery, radiation, and active surveillance. In this review, we summarize contemporary data pertaining to active surveillance, a strategy in which patients with low-risk cancer characteristics undergo monitoring at regular intervals. Treatment is initiated following evidence of cancer features associated with a higher risk of progression. Multiple clinical experiences suggest active surveillance is a safe and appropriate strategy for select patients. Most definitions of low-risk cancer include a variable combination of: prostate-specific antigen (PSA) < or =10 ng/mL, clinical stage T1-T2a, biopsy Gleason score < or =6, and three or fewer positive biopsy cores. Although older patients or those with signficant competing medical risks typically are not treated with surgery or radiation, active surveillance should also be considered and explained to well-selected healthy patients otherwise considering primary therapy. Due to significant concerns about clinical understaging, eligible patients should consider a repeat biopsy prior to selecting active surveillance. Short- to intermediate-term follow-up suggests active surveillance is associated with favorable overall outcomes, including for those undergoing delayed treatment, and has a relatively low risk of leading to incurable prostate cancer.

Mixed epithelial stromal renal tumor with dystrophic ossification: a case report and literature review.

A 25-year-old female presented with worsening right flank pain and a 9 year history of a slow growing 4 centimeter calcified renal mass. The lesion was resected by laparoscopic partial nephrectomy revealing a mixed epithelial and stromal tumor (MEST). This tumor has unusual features including the extensive amount of dystrophic calcification and the young age at presentation. Herein, we present a focused review of the literature regarding MESTs, as well as a discussion of calcified renal mass management. We conclude that laparoscopy may be utilized to safely perform nephron sparing surgery for select, calcified renal masses.

Implications of micropapillary urothelial carcinoma variant on prognosis following radical cystectomy: A multi-institutional investigation.

PURPOSE: To determine the association of micropapillary urothelial carcinoma (MUC) variant histology with bladder cancer outcomes after radical cystectomy. MATERIALS AND METHODS: Information on MUC patients treated with radical cystectomy was obtained from five academic centers. Data on 1,497 patients were assembled in a relational database. Tumor histology was categorized as urothelial carcinoma without any histological variants (UC; n = 1,346) or MUC (n = 151). Univariable and multivariable models were used to analyze associations with recurrence-free (RFS) and overall (OS) survival. RESULTS: Median follow-up was 10.0 and 7.8 years for the UC and MUC groups, respectively. No significant differences were noted between UC and MUC groups with regard to age, gender, clinical disease stage, and administration of neoadjuvant and adjuvant chemotherapy (all, P ≥ 0.10). When compared with UC, presence of MUC was associated with higher pathologic stage (organ-confined, 60% vs. 27%; extravesical, 18% vs. 23%; node-positive, 22% vs. 50%; P < 0.01) and lymphovascular invasion (29% vs. 58%; P < 0.01) at cystectomy. In comparison with UC, MUC patients had poorer 5-year RFS (70% vs. 44%; P < 0.01) and OS (61% vs. 38%; P < 0.01). However, on multivariable analysis, tumor histology was not independently associated with the risks of recurrence (P = 0.27) or mortality (P = 0.12). CONCLUSIONS: This multi-institutional analysis demonstrated that the presence of MUC was associated with locally advanced disease at radical cystectomy. However, clinical outcomes were comparable to those with pure UC after controlling for standard clinicopathologic predictors.