Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor-associated macrophages

Increased evidence suggests that cancer-associated inflammation supports tumor growth and progression. We have previously shown that semaphorin 4D (Sema4D), a ligand produced by different cell types, is a proangiogenic molecule that acts by binding to its receptor, plexin B1, expressed on endothelial cells (Conrotto, P., D. Valdembri, S. Corso, G. Serini, L. Tamagnone, P.M. Comoglio, F. Bussolino, and S. Giordano. 2005. Blood. 105:4321–4329). The present work highlights the role of Sema4D produced by the tumor microenvironment on neoplastic angiogenesis. We show that in an environment lacking Sema4D, the ability of cancer cells to generate tumor masses and metastases is severely impaired. This condition can be explained by a defective vascularization inside the tumor. We demonstrate that tumor-associated macrophages (TAMs) are the main cells producing Sema4D within the tumor stroma and that their ability to produce Sema4D is critical for tumor angiogenesis and vessel maturation. This study helps to explain the protumoral role of inflammatory cells of the tumor stroma and leads to the identification of an angiogenic molecule that might be a novel therapeutic target

Laparoscopic transposition of lower pole crossing vessels (vascular hitch) in children with pelviureteric junction obstruction

Abstract BACKGROUND: Congenital hydronephrosis due to intrinsic or extrinsic uretero-pelvic-junction (UPJ) obstruction (UPJO) is a common problem in childhood UPJO may be caused by intrinsic disorganization or by extrinsic compression from crossing vessels (CV); extrinsic causes usually present symptomatically in older children. This report the large Italian experience in the treatment of children with extrinsic-UPJO by CV. METHODS: We analyzed the data of 51 children (17 girls and 34 boys, median age 10, 7 years) affected by extrinsic-UPJO were treated in three Italian institutions with laparoscopic transposition of CV (Hellström Vascular Hitch modified by Chapman).The intraoperative diuretic-test was performed in all patients before and after the vessels transpositions confirming the extrinsic-UPJO. We included in the study only patients with suspicion of vascular extrinsic obstruction of the UPJ. Symptoms at presentation were recurrent abdominal/flank pain and haematuria. All patients presented intermittent ultrasound (US) detection of hydronephrosis (range, 18-100 mm). Preoperative diagnostic studies included: US/doppler scan, MAG3-renogram, functional-magnetic-resonance-urography (fMRU). RESULTS: Median operative time was 108 minutes; median hospital stay: 3, 4 days. Unique complications: a small abdominal wall hematoma and higher junction-translocation without obstruction. During follow-up (range, 12-96 months) all patients reported resolution of their symptoms, a decrease in the hydronephrosis grade and improved drainage on diuretic renogram. CONCLUSIONS: We believe that Vascular Hitch is less technically demanding than laparoscopic pyeloplasty, resulting in a lower complication rate and a significantly reduced hospitalization. The results of our study allow us to conclude that laparoscopic VH may be a safe, feasible, and attractive alternative to treat obstructed hydronephrosis due to CV presenting a useful alternative to AHDP in the management of symptomatic children where CV are deemed the sole aetiology. We recommend careful patient selection based on preoperative clinical and radiologic findings that are diagnostic of extrinsic-UPJO, combined with intraoperative-DT to confirm the appropriate selection of corrective procedure

Long-Term Follow-Up of Testicular Microlithiasis in Children and Adolescents: Multicenter Prospective Cohort Study of the Italian Society of Pediatric Urology.

Introduction Testicular microlithiasis (TM), characterized by the presence of intratubular calcifications in a single or both the gonads, is an uncommon entity with unknown etiology and outcome in pediatric and adolescent age. In this study, the results of a multicenter long-term survey are presented. Materials and Methods From 11 units of pediatric urology/surgery, patients with TM were identified and yearly, followed up in a 7-year period, adopting a specific database. The recorded items were: age at diagnosis, presenting symptoms/associated abnormalities, ultrasonographic finding, surgery and histology at biopsy, if performed. Results Out of 85 patients, 81 were evaluated yearly (4 patients lost to follow-up). TM was bilateral in 66.6% of the patients. Associate genital abnormalities were present in 90%, more frequently undescended/retractile testis (23.4%) and varicocele (22.2%). TM remained unchanged at 4.7 years follow-up in 77 patients (93.8%) and was reduced in 4 patients after 1 to 5 years of inguinoscrotal surgery. Orchiectomy was performed in three patients (3.7%), one for severe testicular hypoplasia and two for seminoma (2.5%), respectively, concurrent and metachronous to diagnosis of TM. Tumorectomy with parenchymal sparing surgery was performed in a teratoma associated with TM. Conclusion TM is a controversial entity, often associated with several inguinogenital features, which rarely can recover. Testicular malignancy, although present in TM, has not proven definitively associated to microliths. Proper counseling, yearly ultrasound, and self-examination are long-term recommended

Minimally Invasive Laser Treatment of Ureterocele

Introduction: Ureterocelemay cause severe pyelo-ureteral obstruction with afebrile urinary tract infections in infants and children. Early decompressive treatment is advocated to reduce the risk of related renal and urinary tract damage. Endoscopic techniques of incision have been offered utilizing diathermic electrode. We adopted laser energy to release the obstruction of the ureterocele and reduce the need of further surgery. Our technique is described and results are presented, compared with a group of matched patients treated by diathermic energy.Materials and methods: Decompression was performed by endoscopic multiple punctures at the basis of the ureterocele. Holmium YAG Laser was utilized with 0.5–0.8 joule energy, through 8–9.8F cystoscope under general anesthesia. The control group received ureterocele incision by diathermic energy through pediatric resettoscope. Foley indwelling catheter was removed after 18–24 h. Renal ultrasound was performed at 1, 3, 6, and 12 months follow-up. Voiding cysto-urethrogram and radionuclide renal scan were done at 6–18 months in selected cases. Statistical analysis was utilized for data evaluation.Results: From January 2012 to December 2017, 64 endoscopic procedures were performed: 49 were ectopic and 15 orthotopicureteroceles. Fifty-three were in duplex systems, mostly ectopic. Mean age at endoscopy was 6.3 months (1–168). Immediate decompression of the ureterocele was obtained, but in five cases (8%) a second endoscopic puncture was necessary at 6–18 months follow-up for recurrent dilatation. Urinary tract infections and de novo refluxes occurred in 23.4 and 29.7% in the study group, compared to 38.5 and 61.5% in the 26 controls (p < 0.05). Further surgery was required in 12 patients (18%) at 1–5 years follow-up (10 in ectopic ureteroceles with duplex systems): seven ureteral reimplantation for reflux, five laparoscopic hemy-nephro-ureterectomy. Orthotopic ureteroceceles had better outcome. Secondary surgery was necessary in 13 patients (50.0%) of control group (p < 0.05).Conclusions: Early endoscopic decompression should be considered first line treatment of obstructing ureterocele in infants and children. Multiple punctures at the basis of the ureterocele, performed by low laser energy, is resulted a really minimally invasive treatment, providing immediate decompression of the upper urinary tract, and reducing the risk of further aggressive surgery

Guidelines of the Italian Society of Videosurgery in Infancy for the minimally invasive treatment of the ureteropelvic-junction obstruction

Not available