Minimally invasive surgery versus standard posterior approach in the treatment of adolescent idiopathic scoliosis: a 2-year follow-up retrospective study.

PURPOSE: This is a monocentric retrospective controlled study that compares the safety and efficacy of posterior minimally invasive surgery (MISS) to standard posterior spinal fusion (PSF) surgery in adolescent idiopathic scoliosis (AIS). METHODS: We retrospectively collected 111 patients with Lenke type 1-6 AIS who were treated with MIS (n = 47) or PSF (n = 64) between February 2019 and January 2021 with a 2-year clinical and radiological follow-up. MIS technique was applied via two midline noncontiguous skin incisions ranging from 3 to 7 cm in length, so we obtained the arthrodesis only in the exposed tract, passing the rods below the fascia, avoiding the complete muscular sparing. Values of Cobb angles degrees were collected to study the correction rate of the structural major curve. Postoperative AP direct radiography and preoperative AP direct radiography were compared with the last follow-up examination. Operative time, preoperative hemoglobin (Hb) and second postoperative day Hb, full length of hospitalization, time to achieve verticalization and time to remove the drainage were recorded. NRS medium score was assessed immediately after surgery and during the whole postoperative rehabilitation treatment to estimate pain reduction. Complications were collected postoperatively and throughout the whole follow-up period. RESULTS: There was no significant difference between the two groups in terms of radiographic and clinical features. The correction rates of the structural curve resulted to be not significantly different between MISS and PSF (64.6 ± 11.7 vs 60.9 ± 13.2, p = 0.1292) as well as for the correction rate of the secondary curve between the two compared techniques (59.1 ± 13.2 vs 59.2 ± 12.4, p = 0.9865). The two groups had comparable operative time (210 min vs 215 min). The MIS group had a significantly lower reduction of postoperative Hb in comparison with PSF group (2.8 ± 1.3 mg/dl vs 4.3 ± 1.5 mg/dl, p < 0.0001). The postoperative NRS score was lower in MIS group (1.9 ± 0.8 vs 3.3 ± 1.3). PSF group was observed to have a significantly longer period of hospitalization than MIS (5.2 ± 1.4 days vs 6.3 ± 2.9 days, p = 0.206). Complications were more frequent in PSF group rather than in MFS group. CONCLUSIONS: MISS is a safe and capable alternative to PSF for AIS patients with curves < 70°, with analogue capacity of scoliosis correction and same operative time and with advantages in blood loss, length of stay and postoperative pain.

Is preoperative ultrasound tumor size a prognostic factor in endometrial carcinoma patients?

Objective: We aimed to assess the prognostic value of preoperative ultrasound tumor size in EC through a single center, observational, retrospective, cohort study. Methods: Medical records and electronic clinical databases were searched for all consecutive patients with EC, preoperative ultrasound scans available to ad hoc estimate tumor size, and a follow-up of at least 2-year, at our Institution from January 2010 to June 2018. Patients were divided into two groups based on different dimensional cut-offs for the maximum tumor diameter: 2, 3 and 4 cm. Differences in overall survival (OS), disease specific survival (DSS) and progression-free survival (PFS) were assessed among the groups by using the Kaplan-Meier estimator and the log-rank test. Results: 108 patients were included in the study. OS, DSS and PFS did not significantly differ between the groups based on the different tumor diameter cut-offs. No significant differences were found among the groups sub-stratified by age, BMI, FIGO stage, FIGO grade, lymphovascular space invasion status, myometrial invasion, lymph nodal involvement, histotype, and adjuvant treatment. Conclusions: Preoperative ultrasound tumor size does not appear as a prognostic factor in EC women.

Endoscopic treatment of ureterocele in children: Results of a single referral tertiary center over a 10 year-period.

INTRODUCTION: The management of UCs remain controversial, especially for UCs with duplex collecting systems that still represent a great challenge in paediatric urology. Several approaches have been used and a shared management is not yet validated. STUDY AIM: Aim of our study is to evaluate the results of the endoscopic treatment of UC comparing ortothopic single-system UC and ectopic duplex-system UC over a 10-year period in a single referral tertiary center. Success was defined as resolution of dilation, lack of urinary infections and preservation of renal function. STUDY DESIGN: We retrospectively reviewed medical records of children with a diagnosis of UC who underwent endoscopic puncture at our division from January 2009 to January 2019. Patients were divided in two groups: Group A composed of patients with ectopic UC associated with renal duplex system and Group B with orthotopic UC in single collecting system. RESULTS: We identified 48 paediatric patients treated with transurethral primary endoscopic incision. Groups result homogeneous for clinical and pathological characteristics. The only statistical significative difference between the two samples was the age at diagnosis (p value with Yates correction = 0.01). DISCUSSION: We considered as a therapeutic success infections control and the elimination of obstruction with preservation of global kidney function. Based on that, our success rate after single (77%) or double (92%) endoscopic treatment is higher than data reported in literature. Differently from previous studies, vescico-ureteral reflux without UTIs was not considered as a failure of the procedure. The present study has some limitations: it is a retrospective and monocentric serie and it lacked a longer follow-up; on the other hand, it has been conducted on a quite large sample size and it is one of the few studies that compares the endoscopic treatment between orthotopic and ectopic UC. CONCLUSION: Our data report primary endoscopic puncture of ureterocele as a simple, effective, and safe procedure also in long-term follow up. This technique avoids the need for additional surgery in the majority of the patients, also in the case of an ectopic UC associated to a duplex system.

Treatment of ureteropelvic junction obstruction and urolithiasis in children with minimally invasive surgery.

BACKGROUND: Ureteropelvic Junction Obstruction (UPJO) is the most common congenital ureteral anomaly. Nowadays, according to the increasing incidence of urolithiasis, 20% of children with UPJO presents urolithiasis. Open pyeloplasty was the standard treatment before the introduction of minimally invasive surgery (MIS). Nevertheless, only scattered experiences on MIS were previously described and universal agreement on the treatment of UPJO plus urolithiasis is still missing. OBJECTIVE: The study aim was to describe our experience with a series of pediatric patients affected by UPJO and urolithiasis treated with robot-assisted pyeloplasty (RAP) and endoscopic removal of stones using a flexible cystoscope and a stones basket in a singular tertiary referral center. MATERIAL AND METHODS: We retrospectively reviewed our data from pediatric patients affected by UPJO and urolithiasis undergoing RAP between April 2013 and December 2019. The analysis was conducted on seven patients. All procedures were performed by one expert robotic surgeon and one endoscopic surgeon skilled in the management of urolithiasis. RESULTS: The mean age was 7 years (IQR 4-16). The median stone area was 77.7 mm two (IQR 50.2-148.4). Most of them (71.4%) presented preoperative symptoms. The median operative time was 110 min (IQR 104-125) with a console time of 90 (IQR 90-105). The median length of stay was 5 days (IQR 4-5). Median follow-up was 16 months (IQR 10-25). CONCLUSION: RAP with concomitant flexible ureteroscope is a safe and effective option for the simultaneous management of UPJO with urolithiasis with excellent outcomes in children.

Ureteral Reimplantation for Primary Obstructive Megaureter in Pediatric Patients: Is It Time for Robot-Assisted Approach?

Objective: To compare open and robotic approach for treatment of Primary Obstructive Megaureter (POM) in a series of pediatric patients. Materials and Methods: Medical records of all patients who had undergone ureteral reimplantation for POM at our institution, between January 2016 and December 2019, were retrospectively collected and analyzed. Open (Group B) and robotic (Group A) approach were compared. Success was defined as reduction of anteroposterior diameter of pelvis and ureter on postoperative ultrasound scan. Surgical complications were reported according to the Clavien-Dindo Classification. Esthetic results were compared through the Vancouver Scar Scale. Results: Out of 23 patients, 11 belonged to Group A (5M and 6F) and 12 to Group B (9M and 3F). Median age at diagnosis was 38 months in Group A and 46 months in Group B (P = .69). Operative times were comparable (150' Group A and 140' Group B; P = .35), but the hospital stay was significantly shorter in the robotic group (P < .01). Success rate was comparable: 90.9% in Group A and 91.7% in Group B, respectively (P = .95). Incidence of early complications was 9.1% in Group A (grade IIIB) and 8.3% in Group B (grade II) (P = .95). Esthetic evaluation obtained a median score of 1 in Group A and 3 in Group B (P < .01). Conclusions: Our preliminary experience shows that robotic reimplantation can be a safe option in the treatment of POM in pediatric patients with clinical outcomes comparable to the open technique.

Check cystoscopy in the management of anterior urethral valves in a cohort of pediatric patients.

INTRODUCTION: Anterior urethral valves (AUV) are a rare cause of lower urinary tract obstruction which could progress to renal damage, Clinical presentation varies according with patient's age and severity of obstruction, but, in most cases, diagnosis is based on voiding cysto-urethrogram (VCUG). To date, the treatment of choice is endoscopic ablation even if approved guidelines about the overall management of AUVs, including the recognition and treatment of residual valves, are not available. OBJECTIVE: We describe our protocol for AUV treatment based on primary endoscopic valve ablation followed by check cystoscopy 15 days later. STUDY DESIGN: Medical records of 5 patients with AUVs admitted from 2008 to 2018 to our Pediatric Urology Unit were retrospectively reviewed. Blood tests, urinalysis, renal US and VCUG were performed in all children, while urodynamic evaluation was performed in the 3/5 patients who could void spontaneously. All patients underwent endoscopic valves ablation and after 15 days after a second look cystoscopy was performed. Follow up was based on clinical and radiological evaluation with US, urinalysis and blood tests. Postoperative non-invasive urodynamic studies were performed in the 3/5 patient toilet-trained patients and VCUG was performed in 1/5 patient. RESULTS: and Discussion: At primary endoscopic ablation cystoscopy revealed AUVs in the penile urethra in three patients, in the penoscrotal urethra in one case, in the bulbar urethra in another case. In 3/5 patients check cystoscopy found residual valves and a second endoscopic ablation was performed. All patients achieved symptoms release and improved urodynamic parameters. No intra or post-operative complication were reported. The assessment of residual valves is variable in literature and it is usually described for posterior urethral valves (PUVs). Few series report the use of VCUG within the first week after valve ablation, our experience instead suggests that performing a second look cystoscopy, is very effective to evaluate the presence of residual AUVs and eventually proceed with further ablation. CONCLUSION: Endoscopic ablation is the gold standard treatment for AUV, but residual valves management is not clearly defined. According to our experience, a check cystoscopy 15 days after primary ablation allows to identify and treat possible residual valves showing good results in terms of safety and efficacy.

Robot-assisted laparoscopic pyeloplasty in children: a systematic review.

INTRODUCTION: Open pyeloplasty has been the first-line treatment for uretero-pelvic junction obstruction for decades. In the last years, minimally-invasive surgery (MIS) has gained popularity in the pediatrics field. Furthermore, recently, a great extension of Robot-assisted laparoscopic pyeloplasty (RALP) has been seen in younger and lighter-weight children as well as in redo cases. Herein we provided a comprehensive review of primary and redo RALP performed in children, particularly focusing on the different distribution of outcomes among the ages. EVIDENCE ACQUISITION: A systematic review of the literature was performed according to PRISMA recommendations and was conducted on surgical indication and technique, intraoperative nuances, peri- and postoperative outcomes of primary and redo RALP. EVIDENCE SYNTHESIS: Overall, 33 studies with 1448 patients were included for primary RALP and 7 studies with 101 patients for redo cases between 2000 and 2019. In particular, 4 studies aimed to compare RALP in different cohorts of children grouped on ages or weight and 4 studies evaluated technical feasibility and safety of RALP over laparoscopic and open approach in very young populations. Success rate for primary RALP was found >90% in all studies but one, with low complication rate and preoperative indication. In redo series, 96% of patients revealed a decreased hydronephrosis on postoperative imaging. CONCLUSIONS: RALP offers excellent outcomes in the pediatric population. However, there is still a strong need for higher quality evidence in the form of prospective observational studies and clinical trials. The rising of new robotic systems, such as single-port platform, might further enhance the applications of RALP in children.

Could surgical experience of adult endourologist overcome the learning curve of retrograde intrarenal surgery in children?

With the increasing of the prevalence of pediatric urolithiasis (1-5%), retrograde intrarenal surgery (RIRS) is emerging as preferred option for the management of stones in pediatric patients. Although the principles of RIRS developed in adults can be applied in children, also expert adult endourologists feel uncomfortable to approach young patients due to long learning curve that usually is expected to be required in this particular setting. The aim of the study was to compare peri- and postoperative outcomes of RIRS in pediatric and adult patients performed by a single surgeon expert in adult endourology (> 500 RIRS) with no experience in pediatric urology. Data on patient characteristics of 30 consecutive patients (15 adults and 15 children) undergoing RIRS at our institution were collected retrospectively from January 2016 to October 2018. Mean age for the pediatric group was 11.8 years (IQR 8-16) and for the adult group was 56 years (IQR 49-58). No significative differences between the two groups in terms of peri- and postoperative outcomes were found. The most common complication was hematuria in 2/30 patients (1 children vs 1 adults) and fever 2/30 (1 pediatric patient vs 1 adult) (p = 1.00) that required antibiotic treatment (Clavien Dindo 2). Median length of stay was 1 day (IQR 1-1 days) in both groups (p = 1.00). Stone-free rate was 86.7% in children and 80% in adults (p = 0.624). Our preliminary experience suggests that expert adult endourologist can manage successfully also pediatric cases with results comparable to adults and low complication rate.

Does the body weight influence the outcome in children treated with robotic pyeloplasty?

INTRODUCTION: To investigate the influence of the body weight on peri- and postoperative outcome in a series of pediatric patients with a diagnosis of uretero-pelvic junction obstruction (UPJO) treated with robot-assisted laparoscopic pyeloplasty (RALP) at a single tertiary referral center. OBJECTIVE: In this study, outcomes of RALP in children divided according to the weight are evaluated. STUDY DESIGN: Sixty-one consecutive patients treated with RALP from January 2016 to May 2019 were recorded retrospectively and divided according to their weight: group A < 15 kg, group B ≥ 15 kg and were included in this study. Eligible criteria for surgery were symptomatic UPJO, worsening of hydronephrosis, or obstructive pattern at renogram. Success criteria were the reduction of the hydronephrosis at imaging and the absence of flank pain. All procedures were performed by one expert robotic surgeon. RESULTS: 18 patients were included in group A (median weight 12 kg) and 43 patients in group B (median weight 33 kg). The median (IQR) operative was 95 (90-120) for group A compared to 90 (85-110) of control group. No significant difference has been found (P = 0.93). We registered one (5.6%) Clavien 3b complication (omental hernia after removal of the drainage requiring surgical correction) and two (4.7%) Clavien 2 complication in group B (urinary infections). No difference has been found in the length of hospital stay, length of catheterization, and duration of procedure between the groups (P > 0.05). At a median follow-up of 23 months (IQR 9-27 vs 9-33), the success rate was comparable between the two groups (94.4% vs 97.7%; P = 0.51). Relapse was recorded in one child per group and both required nephrostomy placement. DISCUSSION: Our study tried to fill the gaps in the evidence on the feasibility of RALP in low-weight children reporting favorable peri-operative and long-term outcomes; however, this study shows some intrinsic limitations. The relatively small numbers of patients in the <15 kg may have underpowered the comparison with heavier patients. Moreover, only two patients were <10 kg so that no definitive conclusions on the safety and feasibility of RALP in this cohort of patients can be drawn. CONCLUSION: RALP in children <15 kg was feasible and effective to treat UPJO with superimposable results to heavier counterparts. In our experience, the need for a different trocar placement and limited space in patients <15 kg did not affect peri-operative and functional outcomes.

Robot-assisted vs laparoscopic pyeloplasty in children with uretero-pelvic junction obstruction (UPJO): technical considerations and results.

BACKGROUND: Although both laparoscopic pyeloplasty (LP) and robot-assisted laparoscopic pyeloplasty (RALP) have reported excellent clinical outcomes, no evidence is currently available about the best surgical approach for surgical treatment of children with uretero-pelvic junction obstruction (UPJO). OBJECTIVE: This study aimed to compare the outcomes of LP and RALP in children with UPJO. STUDY DESIGN: The medical records of all patients with UPJO, who underwent LP or RALP in three pediatric urology units over a 2-year period, were retrospectively reviewed. The authors excluded open pyeloplasty and cases with complex anatomy such as horseshoe kidney. A dismembered Anderson-Hynes pyeloplasty was performed in all cases. RESULTS: Sixty-seven patients (39 boys and 28 girls) with a median age of 4 years (range 8 months-14 years) were included. Thirty-seven patients (55.2%) underwent RALP, and 30 patients (44.8%) underwent LP. Three patients of RALP group presented a recurrent UPJO. No significant difference was found in the median total operative time between RALP (133 min) and LP (139 min) (P = 0.33). The median anastomotic time was significantly shorter in RALP (79 min) compared with LP (105.5 min) (P = 0.001). Overall surgical success rate was 96.7% for LP and 100% for RALP (P = 0.78). As for postoperative complications, the authors recorded re-stenosis of UPJO in one LP patient (3.3%), who underwent redo-RALP. DISCUSSION: According to the authors experience, robotic surgery should be indicated in patients older than 18-24 months with a body weight > 10-15 Kgs. Laparoscopic pyeloplasty requires advanced laparoscopic skills related to intracorporeal suturing. However, the learning curve of suturing in robotics is much shorter compared with laparoscopy. In fact, during LP, the authors have to place 2-3 transabdominal stay sutures to stabilize the uretero-pelvic junction, before performing the anastomosis. Conversely, the authors never needed to place stay sutures in RALP. CONCLUSIONS: The study experience suggested that RALP and LP give excellent results in children with UPJO. Laparoscopic pyeloplasty can be considered more minimally invasive than RALP because 3-mm trocars are adopted instead of 8-mm robotic ports. However, LP is technically challenging and has a bad ergonomics for the surgeon. Conversely, RALP is technically easier compared with LP, especially in redo procedures, with an excellent ergonomics. The main disadvantages of RALP remain high costs and size of robotic instruments. The choice to perform LP or RALP should be tailored to the individual case, considering patient's age and surgeon's experience.

Is a Drainage Placement Still Necessary After Robotic Reconstruction of the Upper Urinary Tract in Children? Experience from a Tertiary Referral Center.

Purpose: To compare the surgical outcomes of children submitted to robot-assisted reconstruction with or without drainage placement performed by a single surgeon in a tertiary referral center. Materials and Methods: Patients submitted to robot-assisted reconstruction, including pyeloplasty for ureteral pelvic junction obstruction, end-to-end anastomosis for retrocaval ureter, and reimplantation for vesical ureter reflux (VUR) from January 2016 to November 2018, were included. Patients with ureteral pelvic junction obstruction or retrocaval ureter were selected for surgery according to the presence of symptoms and/or evidence of obstruction on diagnostic imaging. The criteria for reimplantation included breakthrough urinary tract infections, progressive renal scarring, and persistent VUR despite watchful waiting. Results: Overall, 31 children composed the no drain placement (DP) group and 29 the DP group. Preoperative feature of the two groups were comparable. Overall, only 1 (3.3%) postoperative complication occurred in no DP group and 2 (6.9%) in the placement group (P = .512). Length of stay was 3 (interquartile range [IQR]: 3-4) and 4 (IQR: 4-4) days, respectively (P = .651). At last follow-up, overall success rate was 100% in the no DP group and 96.6% in the DP group (P = .297). Conclusions: Robot-assisted reconstruction represents a safe minimally invasive approach with optimal surgical outcomes for the treatment of upper urinary tract. Expert robotic surgeons could avoid drainage placement after surgery as this does not undermine perioperative outcomes and postoperative success rate. Our study, first in literature, proves the interest in assessing the safety of no drainage placement also in the pediatric field.

Minilaparoscopic Versus Open Pyeloplasty in Children Less Than 1 Year.

Purpose: The aim of this study is to compare minilaparoscopic (MLS) and open pyeloplasty (OP) in children <1 year in terms of intra- and perioperative outcomes and esthetic results. Materials and Methods: Patients <1 year of age, with prenatal hydronephrosis, who underwent Anderson-Hynes pyeloplasty for monolateral ureteropelvic junction obstruction (UPJO) at our center from January 2016 to August 2017 were enrolled in the study. Outcomes evaluated were as follows: operative time, length of hospital stay, and postoperative pain anterior-posterior pelvic diameter (APD) reduction. The Vancouver Scar Scale (VSS) was utilized to evaluate esthetic results. Mean follow-up was 26.5 months. Results: Eighteen patients (11M, 7F) of mean age 8.1 months (range 4-12) and mean weight 8.5 kg (range 7-10) underwent Anderson-Hynes pyeloplasty in the study period. Nine of eighteen underwent OP, and 9/18 underwent MLS. Mean operative time was 167 minutes for MLS versus 153 minutes for OP (P = .14). Mean hospital stay was 3.9 days for MLS versus 5.3 days for OP (P = .11). Mean APD reduction was 13.6 mm for MLS and 16.5 mm for OP procedures (P = .63). Mean VSS score was 1.3 for VLS versus 3.4 for OP (P = .04). Conclusions: MLS pyeloplasty is feasible and safe, and reported equivalent results as open procedure for management of UPJO also in toddlers and infants. We found that the only significant difference between the two approaches in children <1 year was represented by the esthetic outcome in the short follow-up period.

Robot-Assisted Nephron-Sparing Surgery for Cystic Nephroma in a Pediatric Patient: A Case Report.

Cystic nephroma is a benign kidney tumor, which presents as a unilateral cystic mass without solid elements. We presented the first case of cystic nephroma treated with robotic nephron-sparing surgery in a pediatric patient. The procedure adopted was the robot-assisted simple enucleation of the lesion, without arterial clamping.

Robot-assisted extravesical ureteral reimplantation (revur) for unilateral vesico-ureteral reflux in children: results of a multicentric international survey.

PURPOSE: This multicentric international retrospective study aimed to report the outcome of robot-assisted extravesical ureteral reimplantation (REVUR) in patients with unilateral vesico-ureteral reflux (VUR). METHODS: The medical records of 55 patients (35 girls, 20 boys) underwent REVUR in four international centers of pediatric robotic surgery for primary unilateral VUR were retrospectively reviewed. Patients' average age was 4.9 years. The preoperative grade of reflux was III in 12.7%, IV in 47.3% and V in 40%. Twenty-six patients (47.3%) presented a loss of renal function preoperatively and 10 (18.1%) had a duplex system. RESULTS: Average robot docking time was 16.2 min (range 5-30). Average total operative time was 92.2 min (range 50-170). No conversions or intra-operative complications were recorded. All patients had a bladder Foley catheter for 24 h post-operatively. Average hospital stay was 2 days (range 1-3). Average follow-up length was 28 months (range 9-60). We recorded three (5.4%) postoperative complications: 1 small urinoma resolved spontaneously (II Clavien) and 2 persistent reflux, only one requiring redo-surgery using endoscopic injection (IIIb Clavien). CONCLUSION: REVUR is a safe and effective technique for treatment of primary unilateral VUR. The procedure is easy and fast to perform thanks to the 6° of freedom of robotic arms. The learning curve is short and it is useful to begin the robotics experience with a surgeon expert in robotic surgery as proctor on the 2nd robot console. The high cost and the diameter of instruments remain the main challenges of robotics applications in pediatric urology.

Proximal hypospadias repair with bladder mucosal graft: Our 10 years experience.

INTRODUCTION AND OBJECTIVE: A great variety of different surgical techniques has been described for proximal hypospadias repair and an ideal tissue has not been determined yet. We present our 10 years of surgical experience using a bladder mucosal graft for urethroplasty. STUDY DESIGN: Bladder mucosal graft urethroplasty was performed between 2005 and 2015 in 50 patients with severe proximal hypospadias. The mean age of patients was 45.1 months (range 24-164 months). Hypospadias were perineal in 18 patients, scrotal in 22, and penoscrotal in 10. In all cases a chordee correction was performed and median time between the first and the second stages was 12 months (mean 17 months, range 4-68 months). Both foley catheter and a suprapubic cystostomy were positioned and maintained for 2-4 weeks. Follow-up was performed at 1-3 and 6-12 months after surgery, and afterwards annually with clinical examination and flowmetry test. RESULTS: Mean follow-up was 5.3 years (median 5, range 1-10 years). Mean graft length was 57.4 mm (median 55 mm, range 35-85 mm). Among all the only early complication registered was a postoperative infection in one patient (2%) at the site of anastomosis. The long-term complications observed were urethrocutaneous fistula in nine patients (18%), urethral stricture in 15 patients (30%), meatal stricture in four patients (8%), and prolapse of meatus in seven patients (14%). The mean time of complication occurrence was 15 months (median 15.5 months, range 1-96 months). The functional and cosmetic appearance after surgery was satisfactory in 42/50 patients (84%) during the follow-up period. DISCUSSION: There is still an open debate regarding the optimal surgical approach for management of severe proximal hypospadias. Compared with other approaches, our technique showed acceptable results even though encumbered by slightly higher complication rates. CONCLUSION: Our results show that bladder mucosal graft for primary severe proximal hypospadias in selected patients is a possible alternative to other commonly used techniques, with the aim of restoring recovery of the normal continuity of the distal urinary tract see figure below.

Redox control of viral carcinogenesis: The human papillomavirus paradigm.

BACKGROUND: Cervical cancer is the second most common neoplastic disease among women worldwide. The initiating event of such cancer is the infection with certain types of human papillomavirus (HPV), a very common condition in the general population. However, the majority of HPV infections is subclinical and transitory and is resolved spontaneously. Intriguingly, viral oncogene expression, although necessary, is not per se sufficient to promote cervical cancer and other factors are involved in the progression of infected cells to the full neoplastic phenotype. In this perspective it has been suggested that the redox balance and the oxidative stress (OS) may represent interesting and under-explored candidates as promoting factors in HPV-initiated carcinogenesis. SCOPE OF THE REVIEW: The current review discusses the possible interplay between the viral mechanisms modulating cell homeostasis and redox sensitive mechanisms. Experimental data and indirect evidences are presented on the activity of viral dependent functions on i) the regulation of enzymes and compounds involved in OS; ii) the protection from oxidation of detoxifying/antiapoptotic enzymes and redox-sensitive transcription factors; iii) the suppression of apoptosis; and iv) the modulation of host microRNAs regulating genes associated with antioxidant defense. MAJOR CONCLUSIONS: The resulting tangled scenario suggests that viral hosting cells adapt their metabolisms in order to support their growth and survival in the increasingly oxidant micro-environment associated with HPV tumor initiation and progression. GENERAL SIGNIFICANCE: HPV can modulate the host cell redox homeostasis in order to favor infection and possibly tumor transformation. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation.

Neuropathological role of PI3K/Akt/mTOR axis in Down syndrome brain.

Down syndrome (DS) is the most frequent genetic cause of intellectual disability characterized by the presence of three copies of chromosome 21 (Chr21). Individuals with DS have sufficient neuropathology for a diagnosis of Alzheimer's disease (AD) after the age of 40years. The aim of our study is to gain new insights in the molecular mechanisms impaired in DS subjects that eventually lead to the development of dementia. We evaluate the PI3K/Akt/mTOR axis in the frontal cortex from DS cases (under the age of 40years) and DS with AD neuropathology compared with age-matched controls (Young and Old). The PI3K/Akt/mTOR axis may control several key pathways involved in AD that, if aberrantly regulated, affect amyloid beta (Aß) deposition and tau phosphorylation. Our results show a hyperactivation of PI3K/Akt/mTOR axis in individuals with DS, with and without AD pathology, in comparison with respective controls. The PI3K/Akt/mTOR deregulation results in decreased autophagy, inhibition of IRS1 and GSK3ß activity. Moreover, our data suggest that aberrant activation of the PI3K/Akt/mTOR axis acts in parallel to RCAN1 in phosphorylating tau, in DS and DS/AD. In conclusion, this study provides insights into the neuropathological mechanisms that may be engaged during the development of AD in DS. We suggest that deregulation of this signaling cascade is already evident in young DS cases and persist in the presence of AD pathology. The impairment of the PI3K/Akt/mTOR axis in DS population might represent a key-contributing factor to the neurodegenerative process that culminates in Alzheimer-like dementia.

Effects of UVB-induced oxidative stress on protein expression and specific protein oxidation in normal human epithelial keratinocytes: a proteomic approach.

BACKGROUND: The UVB component of solar ultraviolet irradiation is one of the major risk factors for the development of skin cancer in humans. UVB exposure elicits an increased generation of reactive oxygen species (ROS), which are responsible for oxidative damage to proteins, DNA, RNA and lipids. In order to examine the biological impact of UVB irradiation on skin cells, we used a parallel proteomics approach to analyze the protein expression profile and to identify oxidatively modified proteins in normal human epithelial keratinocytes. RESULTS: The expression levels of fifteen proteins - involved in maintaining the cytoskeleton integrity, removal of damaged proteins and heat shock response - were differentially regulated in UVB-exposed cells, indicating that an appropriate response is developed in order to counteract/neutralize the toxic effects of UVB-raised ROS. On the other side, the redox proteomics approach revealed that seven proteins - involved in cellular adhesion, cell-cell interaction and protein folding - were selectively oxidized. CONCLUSIONS: Despite a wide and well orchestrated cellular response, a relevant oxidation of specific proteins concomitantly occurs in UVB-irradiated human epithelial Keratinocytes. These modified (i.e. likely dysfunctional) proteins might result in cell homeostasis impairment and therefore eventually promote cellular degeneration, senescence or carcinogenesis.

Proteomics analysis of protein expression and specific protein oxidation in human papillomavirus transformed keratinocytes upon UVB irradiation.

Increasing evidence supports the role of oxidative stress in cancer development. Ultraviolet (UV) irradiation is one of the major sources of oxidative stress through the generation of reactive oxygen species (ROS). Besides the physiological function of ROS in cellular homeostasis, accumulating reports suggest that ROS are involved in all stages of multistep cancer development. In order to investigate the involvement of oxidative damage into the mechanisms of tumour progression, we used a parallel proteomic approach to analyse the protein expression profile and to identify oxidatively modified proteins in human papillomavirus (HPV)-transformed keratinocytes (HK-168 cells) upon ultraviolet B (UVB) exposure. The HK-168 cells were obtained from normal human epidermal keratinocytes transfected with the whole genome of the high-risk HPV type 16, unanimously recognized as an etiological agent of cervical carcinoma. Because of its year-long latency, this tumour offers a convenient model to study the role of environmental concurring agents in the multistep malignant progression. By the protein expression profile, we identified 21 proteins that showed different expression levels in HK-168 cells treated with UVB in comparison with untreated cells. Focusing on the oxidative modifications occurring at the protein level, we identified five proteins that showed elevated protein carbonyls levels: alpha-enolase, heat shock protein 75, annexin 2, elongation factor Tu and elongation factor gamma. Our results indicate that UVB-induced oxidative stress perturbs the normal redox balance and shifts HPV-transformed keratinocytes into a state in which the carbonylation of specific proteins is systematically induced. We suggest that UVB-induced modulation of protein expression combined with oxidative modification lead to protein dysfunction that might contribute to the malignant progression of transformed cells.