Nongenitourinary complications associated with robot-assisted laparoscopic and radical retropubic prostatectomy: A single institution assessment of 1,100 patients over 11 years.

OBJECTIVES: Robot-assisted laparoscopic prostatectomy (RALP) and radical retropubic prostatectomy (RRP) provide similar outcomes in terms of biochemical recurrence, postoperative continence, and erectile function. Little is known about other complications of these procedures. To further address this, we examined patient outcomes at our institution over an 11-year period. METHODS: A retrospective review of 1,113 prostatectomies (646 RALP and 467 RRP) performed over 11 years by 9 different urologists at a single U.S. academic center was undertaken. Preoperative data collected included age, body mass index (BMI), prostate-specific antigen (PSA), biopsy Gleason score, and tumor (T) stage. Postoperative data included pelvic lymph node dissection (PLND), intensive care unit (ICU) admission rate, length of stay (LOS), ileus, wound infection rate, umbilical hernia occurrence, inguinal hernia occurrence, ophthalmic complications, upper and lower extremity complications, postoperative neuropathy, residual cancer, and cancer recurrence. RESULTS: Significant differences between RRP and RALP included performance of PLND (54.1% vs. 35.9%, P < 0.0001 respectively), umbilical hernia rates (2.4% vs. 6.5%, P = 0.0015, respectively), inguinal hernia rates (5.4% vs. 2.5%, P = 0.0101, respectively), and LE complications (9.0% vs. 5.1%, P = 0.016, respectively). No difference was observed regarding ICU admission, LOS, ileus, wound infection, and ophthalmic or upper extremities complications. CONCLUSIONS: RRP patients were more likely to have lower extremity complications and inguinal herniae, whereas RALP patients had an increased umbilical hernia rate and a trend toward more corneal abrasions.

Copy number variation analysis implicates the cell polarity gene glypican 5 as a human spina bifida candidate gene.

Neural tube defects (NTDs) are common birth defects of complex etiology. Family and population-based studies have confirmed a genetic component to NTDs. However, despite more than three decades of research, the genes involved in human NTDs remain largely unknown. We tested the hypothesis that rare copy number variants (CNVs), especially de novo germline CNVs, are a significant risk factor for NTDs. We used array-based comparative genomic hybridization (aCGH) to identify rare CNVs in 128 Caucasian and 61 Hispanic patients with non-syndromic lumbar-sacral myelomeningocele. We also performed aCGH analysis on the parents of affected individuals with rare CNVs where parental DNA was available (42 sets). Among the eight de novo CNVs that we identified, three generated copy number changes of entire genes. One large heterozygous deletion removed 27 genes, including PAX3, a known spina bifida-associated gene. A second CNV altered genes (PGPD8, ZC3H6) for which little is known regarding function or expression. A third heterozygous deletion removed GPC5 and part of GPC6, genes encoding glypicans. Glypicans are proteoglycans that modulate the activity of morphogens such as Sonic Hedgehog (SHH) and bone morphogenetic proteins (BMPs), both of which have been implicated in NTDs. Additionally, glypicans function in the planar cell polarity (PCP) pathway, and several PCP genes have been associated with NTDs. Here, we show that GPC5 orthologs are expressed in the neural tube, and that inhibiting their expression in frog and fish embryos results in NTDs. These results implicate GPC5 as a gene required for normal neural tube development.

Mutations in prickle orthologs cause seizures in flies, mice, and humans.

Epilepsy is heritable, yet few causative gene mutations have been identified, and thus far no human epilepsy gene mutations have been found to produce seizures in invertebrates. Here we show that mutations in prickle genes are associated with seizures in humans, mice, and flies. We identified human epilepsy patients with heterozygous mutations in either PRICKLE1 or PRICKLE2. In overexpression assays in zebrafish, prickle mutations resulted in aberrant prickle function. A seizure phenotype was present in the Prickle1-null mutant mouse, two Prickle1 point mutant (missense and nonsense) mice, and a Prickle2-null mutant mouse. Drosophila with prickle mutations displayed seizures that were responsive to anti-epileptic medication, and homozygous mutant embryos showed neuronal defects. These results suggest that prickle mutations have caused seizures throughout evolution.