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OBJECTIVE: Retzius-sparing robot-assisted radical prostatectomy (RSP) is a novel approach for radical prostatectomy that was described by our group for the first time in 2010 and is spreading all around the world. The aim of the present study was to assess the effect of surgical experience (SE) on perioperative, functional and oncological outcomes during the first 50 RSP cases performed by a naive surgeon for this novel approach. MATERIALS AND METHODS: We retrospectively evaluated the initial cases operated by 14 surgeons in 12 different international centers. Pre-, peri- and post- operative features of the first 50 patients operated by each surgeon in all the participating centers were collected. The effect of the SE on perioperative, functional and oncological outcomes was firstly evaluated after stratification of surgical experience in initial (≤25) and expert cases (>25) and after using locally weighted scatter-plot smoother (LOWESS) function to graphically explore the relationship between SE and the outcomes of interest. RESULTS: We evaluated 626 patients. Median follow-up was 13 months in the first group and 9 months in the second (p=0.002). Preoperative features were overlapping between the two groups. Lower console time (140 min vs 120 minutes, p=0.001) and a trend for lower complications rates (13 vs 5.5%, p=0.038) were observed in the second group. The relationship between SE and console time, immediate urinary continence recovery and Clavien Dindo complications ≥2 was linear without reaching a plateau after 50 cases. Conversely, a non-linear relationship was observed between SE and PSMs. CONCLUSIONS: We reported the first multi-center experience of Retzius-sparing RARP during the learning curve. We found that console time, immediate urinary continence recovery and postoperative complications are optimal from the beginning and further quickly improve during the learning process, while PSMs rates did not clearly enhance over the first 50 cases.

Background Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant disease characterized by congenital malformation of the great toes and progressive heterotopic ossification of soft tissues leading to cumulative disability. The genetic cause of FOP are mutations in the ACVR1 gene that encodes a type I receptor of Bone Morphogenetic Proteins. The most recurrent mutation in FOP patients is R206H affecting the Glycine‐Serine rich domain and causing the hyper‐activation of the receptor and the responsivity to the non‐canonical ligand, Activin A. In the present study, we described a 3‐years old child with early and highly suggestive clinical features of FOP who was found negative for the recurrent p.R206H substitution. Methods Molecular screening of the whole ACVR1 coding sequence and functional characterization in transfection‐based assays. Results and Conclusions We identified a novel, de novo variant in the fifth ACVR1 coding exon (NM_001111067.4:c.772A>T; NP_001104537.1:p.(R258W)). This substitution, never reported in association with FOP, affects a conserved arginine residue in the kinase domain of the protein. In silico analysis predicted the pathogenicity of this substitution, demonstrated by in vitro assays showing that the p.R258W ACVR1 mutated receptor acquires the ability to transduce the aberrant Activin A‐mediated signaling, as observed for the gene variants associated with FOP., FOP is a rare genetic disease representing the most severe and disabling condition due to heterotopic ossification associated with gain‐of‐function mutations of the ACVR1 gene. We describe here a little patient with an early clinical presentation of the disease carrying a novel substituton of the ACVR1 causative gene.

Background Fibrodysplasia Ossificans Progressiva (FOP) is a rare genetic disorder caused by sporadic heterozygous mutations in ACVR1 gene which progressively leads to severe heterotopic ossification. FOP is characterized by episodic flare-ups triggered by different factors such as viral infections, tissue injuries, vaccinations or occurring without a recognizable cause. The sporadic course of the disease, the documented presence of an important inflammatory reaction in early lesions and the partial response to corticosteroids support the idea that the immune system, and in particular the innate component, may play a role in FOP pathogenesis. However, an extensive expression profile of the peripheral blood mononuclear cells (PBMC) of FOP patients has never been done. Methods In the present study, we carried out a wide PBMC immunophenotyping on a cohort of FOP patients and matching controls by multiparametric analysis of the expression of a panel of 37 markers associated with migration, adhesion, inhibition, activation and cell death of circulating immune cells. Results We observed a statistically significant increase of the expression of DNAM1 receptor in patients' monocytes as compared to controls, and little but significant differences in the expression profile of CXCR1 (CD181), CD62L, CXCR4 (CD184) and HL-DR molecules. Conclusions DNAM1 had been previously shown to play a pivotal role in monocyte migration through the endothelial barrier and the increased expression detected in patients' monocytes might suggest a role of this surface receptor during the early phases of FOP flare-ups in which the activation of the immune response is believed to represent a crucial event. This article is protected by copyright. All rights reserved.

To provide an overview of the anatomical landmarks needed to guide a retropubic (Retzius)-sparing robot-assisted laparoscopic prostatectomy (RALP), and a step-by-step description of the surgical technique that maximizes preservation of the periprostatic neural network. The anatomy of the pelvic fossae is presented, including the recto-vesical pouch (pouch of Douglas) created by the reflections of the peritoneum. The actual technique of the trans-Douglas, intrafascial nerve-sparing robotic radical prostatectomy is described. The technique allows the prostate gland to be shelled out from under the overlying detrusor apron and dorsal vascular complex (DVC-Santorini plexus), entirely avoiding the pubovesical ligaments. There is no need to control the DVC, since the line of dissection passes beneath the plexus. Three key points to ensure enhanced nerve preservation should be respected: (1) the tips of the seminal vesicles, enclosed in a "cage" of neuronal tissue; a seminal vesicle-sparing technique is therefore advised when oncologically safe; (2) the external prostate-vesicular angle; (3) the lateral surface of the prostate gland and the apex. The principles of tension and energy-free dissection should guide all the maneuvers in order to minimize neuropathy. Using robotic technology, a complete intrafascial dissection of the prostate gland can be achieved through the Douglas space, reducing surgical trauma and providing excellent functional and oncological outcomes.

Diabet. Med. 27, 1195–1200 (2010) Abstract Aims Permanent neonatal diabetes is a rare condition affecting 1 in 300 000–400 000 live births; only in 60% of cases it is possible to identify the genetic defect. The condition of pancreatic agenesis is rarer still. Only two genes are known to determine this phenotype: PDX-1 and PTF1A. Congenital heart defects are among the most common developmental anomalies, affecting 1% of newborns, and the GATA4 gene is less frequently involved in these disorders. An Italian child with pancreatic agenesis and an atrial septal defect was genetically investigated to elucidate whether the association of the two pathologies was casual, or represented a new pancreatic/cardiac syndrome. Methods A panel of pancreas development genes, including GCK, Kir6.2, PTF1A, PDX-1, HNF-1A, NgN3, SOX17, SOX7, SOX9, INS, HNF1-B and SUR1 plus the GATA4 gene, were screened for characterization of pancreatic agenesis and cardiac defect. Results Screening for genes causing permanent neonatal diabetes was negative. A novel mutation in GATA4 (c1512C>T) was detected and functional characterization confirmed a reduced activity of the protein. In the family members, the GATA4 mutation co-segregates with a cardiac phenotype, but not with pancreatic agenesis. Conclusions We describe the first report of pancretic agenesis with an associated cardiac defect and a mutation in the GATA4 gene. We could not establish that the GATA4 mutation was causative for pancreatic agenesis and further genetic investigation to detect the genetic cause of the pancreas agenesis was unsuccessful. We conclude that, the two pathologies are attributable to two independent events.