Vertical transmission of microbiomes into embryo culture media and its association with assisted reproductive outcomes.

RESEARCH QUESTION: Can microbes vertically transmit from semen and follicular fluid to embryo culture media during assisted reproductive technology (ART) treatment? DESIGN: Spent embryo culture media (SECM), seminal fluid and follicular fluid samples were collected from 61 couples with infertility undergoing ART treatment at the Prince of Wales Hospital, Hong Kong SAR, China. Metagenomic analysis was conducted using 16s rRNA sequencing to identify the source of microbes in SECM, correlation between the semen microbiome and male infertility, and correlation between the follicular fluid microbiome and female infertility. RESULTS: Microbial vertical transmission into SECM was reported in 82.5% of cases, and semen was the main source of contamination in conventional IVF cases. The increased abundances of Staphylococcus spp. and Streptococcus anginosus in semen had negative impacts on total motility and sperm count, respectively (P < 0.001). Significant increases in abundance of the genera Prophyromonas, Neisseria and Facklamia were observed in follicular fluid in women with anovulation, uterine factor infertility and unexplained infertility, respectively (P < 0.01). No significant correlation was found between the bacteria identified in all sample types and ART outcomes, including fertilization rate, embryo development, number of available embryos, and clinical pregnancy rate. CONCLUSION: Embryo culture media can be contaminated during ART treatment, not only by seminal microbes but also by follicular fluid and other sources of microbes. Strong correlations were found between specific microbial taxa in semen and sperm quality, and between the follicular fluid microbiome and the aetiology of female infertility. However, no significant association was found between the microbiomes of SECM, semen and follicular fluid and ART outcomes.

Current global status of male reproductive health.

BACKGROUND: The widespread interest in male reproductive health (MRH), fueled by emerging evidence, such as the global decline in sperm counts, has intensified concerns about the status of MRH. Consequently, there is a pressing requirement for a strategic, systematic approach to identifying critical questions, collecting pertinent information, and utilizing these data to develop evidence-based strategies. The methods for addressing these questions and the pathways toward their answers will inevitably vary based on the variations in cultural, geopolitical, and health-related contexts. To address these issues, a conjoint ESHRE and Male Reproductive Health Initiative (MRHI) Campus workshop was convened. OBJECTIVE AND RATIONALE: The three objectives were: first, to assess the current state of MRH around the world; second, to identify some of the key gaps in knowledge; and, third, to examine how MRH stakeholders can collaboratively generate intelligent and effective paths forward. SEARCH METHODS: Each expert reviewed and summarized the current literature that was subsequently used to provide a comprehensive overview of challenges related to MRH. OUTCOMES: This narrative report is an overview of the data, opinions, and arguments presented during the workshop. A number of outcomes are presented and can be summarized by the following overarching themes: MRH is a serious global issue and there is a plethora of gaps in our understanding; there is a need for widespread international collaborative networks to undertake multidisciplinary research into fundamental issues, such as lifestyle/environmental exposure studies, and high-quality clinical trials; and there is an urgent requirement for effective strategies to educate young people and the general public to safeguard and improve MRH across diverse population demographics and resources. LIMITATIONS REASONS FOR CAUTION: This was a workshop where worldwide leading experts from a wide range of disciplines presented and discussed the evidence regarding challenges related to MRH. While each expert summarized the current literature and placed it in context, the data in a number of areas are limited and/or sparse. Equally, important areas for consideration may have been missed. Moreover, there are clear gaps in our knowledge base, which makes some conclusions necessarily speculative and warranting of further study. WIDER IMPLICATIONS: Poor MRH is a global issue that suffers from low awareness among the public, patients, and heathcare professionals. Addressing this will require a coordinated multidisciplinary approach. Addressing the significant number of knowledge gaps will require policy makers prioritizing MRH and its funding. STUDY FUNDING/COMPETING INTERESTS: The authors would like to extend their gratitude to ESHRE for providing financial support for the Budapest Campus Workshop, as well as to Microptic S.L. (Barcelona) for kindly sponsoring the workshop. P.B. is the Director of the not-for-profit organization Global Action on Men's Health and receives fees and expenses for his work, (which includes the preparation of this manuscript). Conflicts of interest: C.J.D.J., C.L.R.B., R.A.A., P.B., M.P.C., M.L.E., N.G., N.J., C.K., AAP, M.K.O., S.R.-H., M.H.V.-L.: ESHRE Campus Workshop 2022 (Travel support-personal). C.J.D.J.: Cambridge University Press (book royalties-personal). ESHRE Annual Meeting 2022 and Yale University Panel Meeting 2023 (Travel support-personal). C.L.R.B.: Ferring and IBSA (Lecture), RBMO editor (Honorarium to support travel, etc.), ExSeed and ExScentia (University of Dundee), Bill & Melinda Gates Foundation (for research on contraception). M.P.C.: Previously received funding from pharmaceutical companies for health economic research. The funding was not in relation to this work and had no bearing on the contents of this work. No funding from other sources has been provided in relation to this work (funding was provided to his company Global Market Access Solutions). M.L.E.: Advisor to Ro, Doveras, Next, Hannah, Sandstone. C.K.: European Academy of Andrology (Past president UNPAID), S.K.: CEO of His Turn, a male fertility Diagnostic and Therapeutic company (No payments or profits to date). R.I.M.: www.healthymale.org.au (Australian Government funded not for profit in men's health sector (Employed as Medical Director 0.2 FET), Monash IVF Pty Ltd (Equity holder)). N.J.: Merck (consulting fees), Gedeon Richter (honoraria). S.R.-H.: ESHRE (Travel reimbursements). C.N.: LLC (Nursing educator); COMMIT (Core Outcomes Measures for Infertility Trials) Advisor, meeting attendee, and co-author; COMMA (Core Outcomes in Menopause) Meeting attendee, and co-author; International Federation of Gynecology and Obstetrics (FIGO) Delegate Letters and Sciences; ReproNovo, Advisory board; American Board of Urology Examiner; American Urological Association Journal subsection editor, committee member, guidelines co-author Ferring Scientific trial NexHand Chief Technology Officer, stock ownership Posterity Health Board member, stock ownership. A.P.: Economic and Social Research Council (A collaborator on research grant number ES/W001381/1). Member of an advisory committee for Merck Serono (November 2022), Member of an advisory board for Exceed Health, Speaker fees for educational events organized by Mealis Group; Chairman of the Cryos External Scientific Advisory Committee: All fees associated with this are paid to his former employer The University of Sheffield. Trustee of the Progress Educational Trust (Unpaid). M.K.O.: National Health and Medical Research Council and Australian Research Council (Funding for research of the topic of male fertility), Bill and Melinda Gates Foundation (Funding aimed at the development of male gamete-based contraception), Medical Research Future Fund (Funding aimed at defining the long-term consequences of male infertility). M.H.V.-L.: Department of Sexual and Reproductive Health and Research (SRH)/Human Reproduction Programme (HRP) Research Project Panel RP2/WHO Review Member; MRHI (Core Group Member), COMMIT (member), EGOI (Member); Human Reproduction (Associate Editor), Fertility and Sterility (Editor), AndroLATAM (Founder and Coordinator).

Safety for cervical corpectomy and diskectomy: univariate and multivariate analysis on predictors for prolonged ICU stay after anterior spinal fusion.

AIM: Cervical anterior spinal fusion (ASF) with corpectomy has risks of catastrophic acute complications such as airway obstruction requiring re-intubation. Our team has adopted a management plan for all cervical corpectomy patients to be admitted to the intensive care unit (ICU) after the operations for overnight observation. Some of these patients were kept intubated after the operations and transferred to the ICU. This study aims to review the outcome of this practice and to identify independent predictors associated with a prolonged ICU stay. METHODS: We reviewed consecutive patients with cervical ASF from January 2010 to June 2018. The primary outcome was the ICU length of stay. Univariate and multivariate analyses were conducted to identify independent risk factors associated with a prolonged ICU stay. In total, 103 patients had ASF during the study period. ICU length of stay for elective ASF was 1.01 day (SD 0.373 days) and was significantly shorter than that for emergency ASF (13.29 days, SD 12.57 days) (p < 0.001). 79.6% (82/103) of the ASF patients were extubated in the operating theatre after surgery. Significantly more corpectomy patients (33.3%) versus ACDF patients (15.1%) were kept intubated to the ICU after the operation (p = 0.037). None required reintubation in the ICU. 90.9% (80/88) of the elective ASF can be discharged from the ICU within 24 hours and only 3.41% (3/88) of the elective ASF had prolonged post-operative stay in the ICU (≥48 hours). RESULTS: For prolonged postoperative ICU stay (≥48 hours), ICU admission airway status of ASF patients who were either extubated in the OT or kept intubated to ICU had no significant association (p = 0.903). Univariate and multivariate analysis had identified emergency admissions (p = 0.043) and the presence of postoperative neurological deficits (p = 0.031) as independent predictors associated with a prolonged postoperative ICU stay. CONCLUSION: In conclusion, cervical corpectomy and ASF were safe with minimal acute complications.

Feasibility and Utility of Mobile Applications for the Evaluation of Urology Residents' Surgical Competence.

OBJECTIVE: To provide real-time assessment and feedback on the competency of urology residents' surgical skill via mobile applications and examine their feasibility and utility. MATERIALS AND METHODS: Two mobile application-based systems (SIMPL and myTIPreport) were sequentially implemented for the case-by-case assessment of residents' performance of surgical skills at a single institution. Data was collected regarding residents' perception of their feedback pre- and post-implementation of the applications. Faculty were surveyed after their implementation to determine their feasibility and utility. RESULTS: 297 individual evaluations were completed with SIMPL and 822 with myTIPreport over four and eleven months respectively. Post-implementation, residents showed significantly improved perceptions regarding the quantity and personalization of surgical skill feedback (P = .043 and .005 respectively). A majority (75%) of the faculty found the mobile applications feasible to use, an improvement compared to prior methods of resident evaluation, and would recommend continued use. CONCLUSION: This study represents the first documented use of real-time surgical competency assessment in urology. The use of mobile applications to evaluate urology residents' surgical competency in clinical practice is both feasible and useful. Their use may allow for more individualized surgical skill teaching during training and for the verification of the surgical skills necessary to practice autonomously.

Long term treatment efficacy & complications of hypofractionated stereotactic radiosurgery in brain arteriovenous malformations.

OBJECTIVE: To evaluate long term treatment efficacy and complications of hypofractionated stereotactic radiosurgery (hfSRS) and identify factors that predict outcomes. METHODS: A retrospective review was conducted on 34 consecutive patients who received hfSRS from 2008 to 2017. Demographic, clinical, angio-architectural characteristics, and radiosurgery data were extracted from the Clinical Data Analysis and Reporting System and our unit's iPlan (BrainLAB, Munich) system. Data was analysed using SPSS. RESULTS: 5-year obliteration rate was 39.1%. Most patients (n = 29, 85.3%) recovered well with GOS of 4-5. 26.9% (n = 9) patients have at least one post-radiosurgery complication including hemorrhage, neurological deficits, radionecrosis. Neurological morbidity and mortality was 17.6% (n = 6). A higher modified radiosurgery arteriovenous malformation score (mRBAS) is associated with a lower 5-year obliteration rate (Rho = -0.486, p = 0.025). None of the bAVM were obliterated once mRBAS exceeds 5.35. As expected, a larger 20-Gy volume outside lesion is associated with more complications and poorer GOS. Interestingly, irradiated drainage vein volume indexed to AVM volume (iiDVV) correlates with increased risks of post-hfSRS haemorrhage (Rho = 0.472, p = 0.031) and reduced event-free survival (Rho = -0.472, p = 0.031). Once iiDVV exceeds 20%, a high rebleeding rate after hfSRS is anticipated (AUC under ROC 0.889). CONCLUSION: Hypofractionated stereotactic radiosurgery is an alternative radiosurgery treatment for bAVM unsuitable for single-fraction SRS. mRBAS predicts obliteration rate and morbidity in hfSRS. Index irradiated drainage vein volume (iiDVV) is associated with event-free survival and rebleeding and should be minimized if feasible.

Emergency endoscopic third ventriculostomy for blocked shunts? Univariate and multivariate analysis of independent predictors for failure.

OBJECTIVEHydrocephalus with a blocked ventriculoperitoneal (VP) shunt is a life-threatening condition. Emergency endoscopic third ventriculostomy (ETV) is a potential treatment option. The aim of the study was to identify independent risk factors associated with failure of ETV in treating patients with blocked shunts.METHODSThe authors retrospectively reviewed data from consecutive patients admitted for blocked shunt treated by ETV during the study period from 2000 to 2016. Univariate and multivariate analyses were performed to identify independent factors associated with failed ETV for blocked shunts, such as age, sex, history of CNS infection, number of previous shunt revisions, operations performed as an emergency or elective, number of specialists, and other factors.RESULTSIn total, 121 patients underwent ETV during the study period. Of these, 31 patients (25.6%) had ETV for treatment of a blocked shunt. In 25 (80.6%) of 31 ETV was performed as an emergency procedure. There was no significant difference in the success rate of ETV depending on whether it was performed as an emergency procedure (64% [16/25]) or an elective procedure (66.7% [4/6]; OR 0.062, 95% CI 0.001-2.708; p = 0.149). Univariate and multivariate analyses identified that history of a CNS infection was an independent risk factor for failure of ETV in treating patients with a blocked shunt (OR 0.030, 95% CI 0.001-0.888; p = 0.043).CONCLUSIONSEmergency ETV had a comparable success rate as elective ETV. A history of CNS infection is an independent predictor of ETV failure in treating patients with blocked shunts.

Comparison of the external physical damages between laser-assisted and mechanical immobilized human sperm using scanning electronic microscopy.

We aim to visualize the external physical damages and distinct external phenotypic effects between mechanical and laser-assisted immobilized human spermatozoa using scanning electronic microscopy (SEM). Human spermatozoa were immobilized mechanically or with laser assistance for SEM examination and the membrane integrities were checked on both types of immobilized spermatozoa. We found evidence of external damages at SEM level on mechanically kinked sperm, but not on laser-assisted immobilized sperm. Although no external damage was found on laser-assist immobilized sperm, there were two distinct types of morphological changes when spermatozoa were stricken by infra-red laser. Coiled tails were immediately formed when Laser pulse was applied to the sperm end piece area, whereas laser applied to the sperm principal piece area resulted in a sharp bend of sperm tails. Sperm immobilized by laser did not exhibit any morphological change if the laser did not hit within the on-screen central target zone or if the laser hit the sperm mid piece or head. Our modified membrane integrity assay revealed that the external membrane of more than half of the laser-assisted immobilized sperm remained intact. In conclusion, mechanical immobilization produced membrane damages whilst laser-assisted immobilization did not result in any external membrane damages besides morphological changes at SEM level.

Noncoding Centromeric RNA Expression Impairs Chromosome Stability in Human and Murine Stem Cells.

We analyzed the effect of transcribed noncoding RNA centromeric satellites on chromosome segregation in normal human and murine stem and fibrosarcoma cells. The overexpression of different centromeric alphoid DNAs in all cell lines induced a marked increase in chromosome mis-segregation in anaphase. Overexpression of centromeric mouse minor satellite also increased chromosome instability in the murine stem but not in human cells. Analysis of chromosome segregation in vivo showed disturbances in the mitotic progression, which was frequently unresolved. Live cell imaging revealed that overexpression of centromeric satellites resulted in several different chromosomal morphological errors in the cell nuclei. Our findings correlated with other reports that several centromeric noncoding RNAs are detected in different carcinoma cells and their expression resulted in segregation errors. Our study furnishes further insights into a novel source of genomic instability in human and murine cells. It has recently been shown that noncoding centromeric RNAs are present in some form of cancer, and thus, overexpression of several types of centromeric noncoding RNAs may be useful as a specific maker for neoplastic cells.

Screening for intracranial aneurysms? Prevalence of unruptured intracranial aneurysms in Hong Kong Chinese.

OBJECT The objective of this study was to generate data on the local prevalence of unruptured intracranial aneurysms (UIAs) in asymptomatic Hong Kong Chinese individuals. First-degree relatives of patients with aneurysmal subarachnoid hemorrhage (aSAH) were recruited as surrogates of the general population and to explore the potential role of screening in this locality. METHODS The authors identified first-degree relatives of consecutive patients with subarachnoid hemorrhage from a ruptured aneurysm who were admitted to a university hospital in Hong Kong from June 2008 to December 2010. Magnetic resonance angiography (MRA) was the imaging modality used to screen the cerebral vasculature of these asymptomatic individuals. If MRA showed abnormal findings, CT angiography was performed to confirm the MRA findings. RESULTS In total, 7 UIAs were identified from the 305 MR angiograms obtained. The prevalence of UIAs in first-degree relatives of patients with aSAH in the Hong Kong Chinese population was 2.30% (95% CI1.02%-4.76%). This percentage was lower than the prevalence rate of 3.2% from a meta-analysis of the literature. The sizes of the UIAs detected ranged from 1.4 mm to 7.5 mm; 85.7% of the UIAs detected in this study were < 5 mm, in contrast to 66% noted in the literature. One of the UIAs identified underwent endovascular stent placement with a flow diverter. None of the UIAs identified ruptured or became symptomatic during a median follow-up period of 3.5 years. CONCLUSIONS The prevalence of UIAs in first-degree relatives of patients with aSAH in the Hong Kong Chinese population was lower than that in Caucasians. At the same time, most of the UIAs detected in this study were small (85.7% were < 5 mm, vs 66% in a meta-analysis). With a similar incidence of aSAH in Hong Kong (7.5 per 100,000 person-years) as compared with data cited in the literature, the hypothesis that UIA rupture risk size threshold is different in Chinese patients should be further investigated.

High-dose simvastatin for aneurysmal subarachnoid hemorrhage: multicenter randomized controlled double-blinded clinical trial.

BACKGROUND AND PURPOSE: Experimental evidence has indicated the benefits of simvastatin for the treatment of subarachnoid hemorrhage. Two randomized placebo-controlled pilot trials that used the highest clinically approved dose of simvastatin (80 mg daily) gave positive results despite the fact that a lower dose of simvastatin (40 mg daily) did not improve clinical outcomes. We hypothesized that a high dose of 80 mg of simvastatin daily for 3 weeks would reduce the incidence of delayed ischemic deficits after subarachnoid hemorrhage compared with a lower dose (40 mg of simvastatin daily) and lead to improved clinical outcomes. METHODS: The study design was a randomized controlled double-blinded clinical trial. Patients with aneurysmal subarachnoid hemorrhage (presenting within 96 hours of the ictus) from 6 neurosurgical centers were recruited for 3 years. The primary outcome measure was the presence of delayed ischemic deficits, and secondary outcome measures included a modified Rankin disability score at 3 months and an analysis of cost-effectiveness. RESULTS: No difference was observed between the groups treated with the higher dose or the lower dose of simvastatin in the incidence of delayed ischemic deficits (27% versus 24%; odds ratio, 1.2; 95% confidence interval, 0.7-2.0; P=0.586) or in the rate of favorable outcomes (modified Rankin Scale score, 0-2) at 3 months (73% versus 72%; odds ratio, 1.1; 95% confidence interval, 0.6-1.9; P=0.770). CONCLUSIONS: High-dose simvastatin treatment should not be prescribed routinely for aneurysmal subarachnoid hemorrhage. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01077206.

Functional human artificial chromosomes are generated and stably maintained in human embryonic stem cells.

We present a novel and efficient non-integrating gene expression system in human embryonic stem cells (hESc) utilizing human artificial chromosomes (HAC), which behave as autonomous endogenous host chromosomes and segregate correctly during cell division. HAC are important vectors for investigating the organization and structure of the kinetochore, and gene complementation. HAC have so far been obtained in immortalized or tumour-derived cell lines, but never in stem cells, thus limiting their potential therapeutic application. In this work, we modified the herpes simplex virus type 1 amplicon system for efficient transfer of HAC DNA into two hESc. The deriving stable clones generated green fluorescent protein gene-expressing HAC at high frequency, which were stably maintained without selection for 3 months. Importantly, no integration of the HAC DNA was observed in the hESc lines, compared with the fibrosarcoma-derived control cells, where the exogenous DNA frequently integrated in the host genome. The hESc retained pluripotency, differentiation and teratoma formation capabilities. This is the first report of successfully generating gene expressing de novo HAC in hESc, and is a significant step towards the genetic manipulation of stem cells and potential therapeutic applications.

HAC stability in murine cells is influenced by nuclear localization and chromatin organization.

BACKGROUND: Human artificial chromosomes (HAC) are small functional extrachromosomal elements, which segregate correctly during each cell division. In human cells, they are mitotically stable, however when the HAC are transferred to murine cells they show an increased and variable rate of loss. In some cell lines the HAC are lost over a short period of time, while in others the HAC become stable without acquiring murine DNA. RESULTS: In this study, we linked the loss rate to the position of the HAC in the murine cell nucleus with respect to the chromocenters. HAC that associated preferentially with the chromocenter displayed a lower loss rate compared to the HAC that are less frequently associated. The chromocenter acts as a hub for the deposition of heterochromatic markers, controlling centromeric and pericentromeric DNA replication timing and chromosome segregation. The HAC which localized more frequently outside the chromocenters bound variable amounts of histone H3 tri-methylated at lysine 9, and the high level of intraclonal variability was associated with an increase in HAC segregation errors and delayed DNA replication timing. CONCLUSION: This is a novel result indicating that HAC segregation is closely linked to the position in the murine nucleus and gives important insight for HAC gene expression studies in murine cells and establishing murine models of human genetic disease.

Endoglin (CD105) as a urinary and serum marker of prostate cancer.

We have previously shown that endoglin (CD105) is upregulated in prostatic fluid of men with large volume prostate cancer. We chose to assess endoglin levels in urine and serum from men with prostate cancer or at increased risk for the disease: Urine samples were collected after digital rectal examination (DRE) from 99 men whose cancer status was confirmed by biopsy, and serum samples were collected from 20 men without prostate cancer at low risk for the disease and from 69 men diagnosed with prostate cancer that subsequently underwent radical prostatectomy (30 pT2, 39 pT3). Endoglin levels were assessed by ELISA. Urinary endoglin was elevated in men with biopsy-positive prostate cancer compared to biopsy-negative men (p=0.0014). Urinary endoglin levels in men with prostate cancer correlated with radical prostatectomy tumor volume. The area under the receiver operating characteristic (ROC) curve was 0.72 for urinary endoglin and 0.50 for serum prostate-specific antigen (PSA; sensitivity for cancer detection 73%, specificity 63%). There were no differences in serum endoglin between normal and cancer cases, but there were increases in serum endoglin in non-organ confined (NOC, pT3+) versus organ-confined (OC, pT2) cases (p=0.0004). The area under the ROC curve was 0.75 for serum endoglin and 0.63 for PSA for predicting NOC status, with a sensitivity of 67% and a specificity of 80%. In conclusion, elevations in post-DRE urinary endoglin suggest there may be value in further studying endoglin as a urinary biomarker of prostate cancer. Endoglin levels in both urine and serum may aid in prostate cancer detection and prognostication.

Lovastatin sensitized human glioblastoma cells to TRAIL-induced apoptosis.

Synergy study with chemotherapeutic agents is a common in vitro strategy in the search for effective cancer therapy. For non-chemotherapeutic agents, efficacious synergistic effects are uncommon. Here, we have examined two non-chemotherapeutic agents for synergistic effects: lovastatin and Tumor Necrosis Factor (TNF)-related apoptosis-inducing ligand (TRAIL) for synergistic effects; on three human malignant glioblastoma cell lines, M059K, M59J, and A172. Cells treated with lovastatin plus TRAIL for 48 h showed 50% apoptotic cell death, whereas TRAIL alone (1,000 ng/ml) did not, suggesting that lovastatin sensitized the glioblastoma cells to TRAIL attack. Cell cycle analysis indicated that lovastatin increased G0-G1 arrest in these cells. Annexin V study demonstrated that apoptosis was the predominant mode of cell death. We conclude that the combination of lovastatin and TRAIL enhances apoptosis synergistically. Moreover, lovastatin sensitized glioblastoma cells to TRAIL, suggesting a new strategy to treat glioblastoma.

Xp11 translocation renal cell carcinoma in adults: expanded clinical, pathologic, and genetic spectrum.

The recently recognized Xp11 translocation renal cell carcinomas (RCCs), all of which bear gene fusions involving the TFE3 transcription factor gene, comprise at least one-third of pediatric RCC. Only rare adult cases have been reported, without detailed pathologic analysis. We identified and analyzed 28 Xp11 translocation RCC in patients over the age of 20 years. All cases were confirmed by TFE3 immunohistochemistry, a sensitive and specific marker of neoplasms with TFE3 gene fusions, which can be applied to archival material. Three cases were also confirmed genetically. Patients ranged from ages 22 to 78 years, with a strong female predominance (F:M=22:6). These cancers tended to present at advanced stage; 14 of 28 presented at stage 4, whereas lymph nodes were involved by metastatic carcinoma in 11 of 13 cases in which they were resected. Previously not described and distinctive clinical presentations included dense tumor calcifications such that the tumor mimicked renal lithiasis, and obstruction of the renal pelvis promoting extensive obscuring xanthogranulomatous pyelonephritis. Previously unreported morphologic variants included tumor giant cells, fascicles of spindle cells, and a biphasic appearance that simulated the RCC characterized by a t(6;11)(p21;q12) chromosome translocation. One case harbored a novel variant translocation, t(X;3)(p11;q23). Five of 6 patients with 1 or more years of follow-up developed hematogenous metastases, with 2 dying within 1 year of diagnosis. Xp11 translocation RCC can occur in adults, and may be aggressive cancers that require morphologic distinction from clear cell and papillary RCC. Although they may be uncommon on a percentage basis, given the vast predominance of RCC in adults compared with children, adult Xp11 translocation RCC may well outnumber their pediatric counterparts.

Laparoscopic heminephrectomy for renal cell carcinoma in cross-fused ectopic kidney.

Crossed renal ectopia is a rare congenital malformation. We report a case of renal cell carcinoma in a 51-year-old man with right-to-left crossed fused renal ectopia. The patient was treated with ultrasound-guided laparoscopic heminephrectomy. Postoperative three-dimensional computed tomography showed normal perfusion of the remaining part of the kidney, with good excretion of contrast from both units of the cross-fused kidney.

High concordance of gene methylation in post-digital rectal examination and post-biopsy urine samples for prostate cancer detection.

PURPOSE: We evaluated the concordance between post-digital rectal examination and post-prostate biopsy urine samples using conventional methylation specific polymerase chain reaction analysis of 3 gene promoters in patients with suspected or confirmed prostate cancer. MATERIALS AND METHODS: Voided urine specimens were collected from 17 men after 15-second digital rectal examination and again after transrectal ultrasound guided biopsy of the prostate for suspected malignancy or for followup biopsy as part of an expectant management protocol. Urine sediment DNA was isolated and subjected to bisulfite modification. Methylation of GSTP1, EDNRB and APC promoters was determined by conventional methylation specific polymerase chain reaction analysis in post-digital rectal examination and post-biopsy samples, and correlated with clinical information. RESULTS: Prostate cancer was detected on prostate biopsy in 12 of 17 patients (71%). Promoter methylation was detected in post-digital rectal examination urine specimens for GSTP1 (24%), APC (12%) and EDNRB (66%). Promoter methylation was detected in post-biopsy urine specimens for GSTP1 (18%), APC (18%) and EDNRB (77%). The concordance between post-digital rectal examination and post-biopsy urine samples was 94% for GSTP1 and APC, and 82% for EDNRB. Overall 100% of patients with biopsy proven prostate cancer had at least 1 gene methylated in urine vs 60% of those without evidence of prostate cancer on biopsy. CONCLUSIONS: Gene analysis using conventional methylation specific polymerase chain reaction is a reliable method for detecting abnormal DNA methylation in voided urine samples obtained following digital rectal examination or prostate needle biopsy. The concordance between post-digital rectal examination and post-biopsy urinary samples for promoter methylation is high (82% to 94%), suggesting that urine collected after digital rectal examination may be used for genetic analysis with results similar to those in post-biopsy urine samples.

Computerized tomography guided percutaneous renal cryoablation with the patient under conscious sedation: initial clinical experience.

PURPOSE: We report on our initial clinical experience with CT guided percutaneous renal cryoablation. MATERIALS AND METHODS: CT guided percutaneous renal cryoablation was performed on 27 tumors using conscious sedation in 20 patients. Eligible patients had tumors of 5 cm or less and were poor surgical candidates or otherwise warranted nephron sparing treatment. Tumors were classified as central or noncentral depending on their relationship to the renal sinus fat. During cryoablation intraoperative active ice ball formation was monitored with real-time CT imaging to ensure adequate tumor coverage. Postoperative followup imaging was obtained at regular intervals. RESULTS: Our method appears technically feasible as of the 27 cryoablations performed, only 1 complication occurred requiring blood transfusion in a patient with a large, centrally located tumor. To date we have 16 tumors in 12 patients with imaging followup of 1 month or more (mean followup 5.9 months). Mean baseline tumor size in this group was 2.5 cm with 11 small (3 cm or less) and 5 large (more than 3 cm) tumors. Of the tumors 5 were centrally located and 11 were noncentrally located. Preliminary data suggest that of the 16 cryoablated tumors 15 showed no signs of enhancement on followup. CONCLUSIONS: CT guided percutaneous renal cryoablation appears to be a feasible treatment option for small, noncentrally located renal tumors. While early results appear promising, longer followup is needed to more clearly define the role of this treatment method.

Long-term survival analysis after laparoscopic radical nephrectomy.

PURPOSE: This report assesses the long-term oncological efficacy of laparoscopic radical nephrectomy compared with open radical nephrectomy in patients with clinically localized renal cell carcinoma. MATERIALS AND METHODS: We analyzed the data from 121 patients who underwent radical nephrectomy between 1991 and 1999 for clinical tumor stage T1/2 N0M0. The medical records of all patients were retrospectively reviewed with emphasis on tumor recurrence and survival. Statistical comparison was performed using Kaplan-Meier analysis. RESULTS: The median followup was 73 months for the laparoscopic group and 80 months for the open group. Of the 67 patients who underwent laparoscopic surgery, 53 survived without any recurrence of disease, 2 are currently alive with metastasis, 2 died of metastatic disease in months 12 and 17, and 10 patients died without any disease recurrence. Laparoscopic port site metastasis did not develop in any patients. Of the 54 who underwent open surgery, 34 survived without any recurrence of disease, 1 currently has metastasis, 6 died of metastasis within 17 to 74 months, and 13 died without any disease recurrence. A comparison of the 5 and 10-year disease-free survival rates of the laparoscopic and open groups revealed no significant differences. In addition, the 5 and 10-year cancer specific and actuarial survival rates were not significantly different. CONCLUSIONS: Based on long-term followup, our evaluation confirmed for clinical tumor stage T1/2 N0M0 that laparoscopic radical nephrectomy is oncologically equivalent to open radical nephrectomy.