Surgical and functional outcomes of Dorsal Inlay Graft urethroplasty in revision vs primary hypospadias repair in the pediatric age.

INTRODUCTION: Over the years, Dorsal Inlay Graft (DIG) urethroplasty has gained worldwide acceptance for primary hypospadias repair. However, its safety and effectiveness for revision surgery are yet to be proven. OBJECTIVE: The aim of the study is to assess and compare complication rates and functional outcomes of DIG surgery in revision versus primary hypospadias repair. MATERIAL AND METHODS: We carried out a retrospective analysis of data collected from 53 consecutive DIG urethroplasties performed by a single surgeon at our institution. Patients were stratified in two groups - primary repair and redo-urethroplasty. For each group, we recorded standard pre-operative characteristics, surgical technicalities, complication rates and uroflowmetry parameters. RESULTS: Out of 53 DIG urethroplasties, 21 (39.6 %) where primary and 32 (60.4 %) were re-do. As expected, the two groups differed for median age at surgery: 20 months for primary and 68.5 months for revision surgery (p < 0.001). Additionally, all 21 (100 %) primary interventions were performed with a preputial graft, whereas among revision DIG urethroplasties only 2 (6.3 %) where preputial and 30 (93.8 %) were buccal (p < 0.001). Catheterization time (7 vs 8 days, p = 0.155) and postoperative complication rates (14.3 % vs 9.4 %, p = 0.581) were comparable between the primary and revision surgery group, respectively (all p > .05). Forty-two of the 53 patients underwent uroflowmetry during follow-up. Of these, 19 (63 %) patients presented with abnormal uroflowmetry and 11 (37 %) had equivocal parameters with no difference between the two groups. DISCUSSION: Dorsal Inlay Graft urethroplasty has long been known to be safe and effective for primary hypospadias repair. On the other hand, data on dorsal inlay graft urethroplasty as a salvage surgery after primary hypospadias repair failure is scarce. Surprisingly, according to our findings, surgical outcomes and complication rates are comparable between primary and revision hypospadias cases. Additionally, our results in the redo group are absolutely encouraging if compared to those reported in the literature for the same subset of patients. CONCLUSIONS: According to our findings, DIG urethroplasty is a safe and effective option to treat revision hypospadias repair.

Off-Label Use of Sirolimus and Everolimus in a Pediatric Center: A Case Series and Review of the Literature.

BACKGROUND: It has been 15 years since sirolimus, an mTOR inhibitor, received Food and Drug Administration approval to prevent acute rejection in kidney transplantation, and 8 years since its analog everolimus acquired the same status. Since then, these drugs have become more and more utilized and their immunosuppressive and antiproliferative properties have been tested in a great variety of clinical conditions, often achieving excellent results. Despite such positive evidence, the on-label indications for these rapalogs are still very restrictive, especially in children. AIMS: The aims of this study were to describe our center's experience with sirolimus and everolimus in managing rare pediatric conditions for which mTOR inhibitors have been reported as a therapeutic option, although without conclusive approval from regulatory agencies, and to evaluate safety and tolerability of the treatment at the prescribed doses. METHODS: All the subjects who received off-label sirolimus or everolimus at the Pediatric Department of the IRCCS Burlo Garofolo in the last 13 years were included. For each disease found in our case series, we reviewed the current scientific literature. RESULTS: Off-label treatment with rapalogs was prescribed in 16 children (11 males, 5 females, median age of 9.5 years, range 1-16 years). Seven had immunologic disorders: four autoimmune lymphoproliferative syndrome (ALPS), one multicentric Castleman disease (mCD), one activated PI3K delta kinase syndrome (APDS), and one immunodysregulation with polyendocrinopathy enteropathy X-linked (IPEX). Eight had proliferative disorders or vascular anomalies: one cystic lymphangioma, two Bannayan-Riley-Ruvalcaba syndrome (BRRS), one blue rubber bleb nevus syndrome (BRBNS), two tuberous sclerosis complex (TSC), and one low-flow mixed arterial and venous malformation. One case had congenital hyperinsulinism (CHI). The average dosage administered was 1 mg/m2 for sirolimus and 7 mg/m2 for everolimus. We experienced a good measurable clinical improvement in 14 patients. Nobody experienced serious adverse events (SAEs). The therapy was interrupted in two cases, for lack of efficacy and poor tolerance in one case and for occurrence of bacterial pneumonia in the other one. A review of the literature identified 101 published reports that met our inclusion criteria. CONCLUSIONS: Although use of mTOR inhibitors has been considered to be complicated, our experience shows that, using low dosages, it is possible to obtain relevant clinical improvements, with a good profile of safety and tolerability.

Feasibility and safety of radiofrequency ablation for locally advanced pancreatic cancer.

BACKGROUND: : Radiofrequency ablation (RFA) may be a valuable treatment option for locally advanced pancreatic cancer. The present study examined its feasibility and safety. METHODS: : Fifty patients with locally advanced pancreatic cancer were studied prospectively. Ultrasound-guided RFA was performed during laparotomy. The main outcome measures were short-term morbidity and mortality. RESULTS: : The tumour was located in the pancreatic head or uncinate process in 34 patients and in the body or tail in 16; median diameter was 40 (interquartile range 30-50) mm. RFA was the only treatment in 19 patients. RFA was combined with biliary and gastric bypass in 19 patients, gastric bypass alone in eight, biliary bypass alone in three and pancreaticojejunostomy in one. The 30-day mortality rate was 2 per cent. Abdominal complications occurred in 24 per cent of patients; in half they were directly associated with RFA and treated conservatively. Three patients with surgery-related complications needed reoperation. Reduction of RFA temperature from 105 degrees C to 90 degrees C resulted in a significant reduction in complications (ten versus two of 25 patients; P = 0.028). Median postoperative hospital stay was 10 (range 7-31) days. CONCLUSION: : RFA of locally advanced pancreatic cancer is feasible and relatively well tolerated, with a 24 per cent complication rate.

Two novel cosegregating mutations in tRNAMet and COX III, in a patient with exercise intolerance and autoimmune polyendocrinopathy.

We report a 12-year-old patient with growth retardation, exercise intolerance, lactic acidosis (increasing after exercise) and autoimmune polyendocrinopathy type 2. Muscle biopsy shows abundant COX-negative fibers, subsarcolemmal mitochondrial aggregates and markedly reduced activities of all respiratory chain complexes. Genetic analysis identified two new cosegregating mutations in Met-tRNA (m.4415A>G) and Cox III (m.9922A>C), located in highly conserved regions of MtDNA. Both the mutations are heteroplasmics in multiple patients' tissues. Single-muscle fiber analysis showed significantly higher levels of both the mutations in COX-negative than in normal fibers. In addition, a possible link between the mitochondrial dysfunction and the autoimmune disease is suggested.

Two novel POLG mutations causing hepatic mitochondrial DNA depletion with recurrent hypoketotic hypoglycaemia and fatal liver dysfunction.

BACKGROUND: Inherited mtDNA depletion syndromes (MDS) are a group of severe mitochondrial disorders resulting from defects in nucleus-encoded factors and often associated with severe or fatal liver failure. PATIENT: In this article, we describe the case of an 18-month-old patient with recurrent hypoketotic hypoglycaemia and fatal hepatic dysfunction with liver mtDNA depletion. METHODS: The assessment of mtDNA copy number was performed on leucocytes, liver and muscle biopsy by Quantitative Real Time PCR and total RNA from liver biopsy was used as a template to amplify the cDNA of the POLG1 gene. RESULTS: Sequence analysis identified two previously undescribed mutations (1868T>G and 2263A>G) located in the gene coding the catalytic subunit of mitochondrial DNA polymerase gamma (POLG), predicting an L623W and K755E amino acid change, respectively. Both mutations were located in the highly conserved linker region of the protein and were absent in more than 200 healthy unrelated control subjects. The identification of these two mutations allowed us to perform genetic counselling and prenatal diagnosis. CONCLUSION: Our data further expand the spectrum of POLG1 gene mutations and the unique phenotype reported (late onset isolated liver disease without lactic acidosis) increase the variability of clinical presentations associated with mutations in this gene.

Intrahepatic peripheral cholangiocarcinoma (IPCC): comparison between perfusion ultrasound and CT imaging.

PURPOSE: This study was done to compare the perfusion patterns of intrahepatic peripheral cholangiocarcinoma (IPCC) on contrast-enhanced ultrasound (CEUS) and dynamic computed tomography (CT). MATERIALS AND METHODS: We retrospectively reviewed 23 histologically proven cases of IPCC. All lesions were studied by CEUS with sulfur hexafluoride-filled microbubbles coated with a phospholipid capsule, and by dynamic CT. Contrast-enhancement patterns were evaluated in the arterial phase (CEUS 10-20 s after the injection; CT 25-30 s after the injection) and in the delayed phase (CEUS 120 s after the injection; CT>2-3 min after the injection). RESULTS: Lesions were single in 18/23 cases (78%), single with nearby satellite lesions in 1/23 (4%) cases and multifocal with distant secondary lesions in 4/23 (17%) cases. Lesion diameter was 2-5 cm in 7/23 cases (30%), 5-7 cm in 13/23 cases (57%) and >7 cm in 3/23 (13%) cases. On CEUS, lesions were hypervascular in 16/23 cases (70%). On delayed-phase CEUS, 22/23 lesions (96%) were markedly hypoechoic. CT showed that the lesions were hypovascular in the arterial phase in 15/23 cases (66%) and hypervascular in 7/23 (30%) cases; one lesion (1/23; 4%) was isovascular. On delayed-phase CT, lesions were hyperdense in 17/23 cases (74%), hypodense in 5/23 (22%) cases and isodense in 1/23 (43%) cases. CONCLUSIONS: Enhancement discrepancy between delayed-phase CEUS (hypoechogenicity) and CT (hyperdensity) is common semiological findings in the study of IPCC.

Respiratory training with a specific device in cystic fibrosis: a prospective study.

INTRODUCTION: Chest physiotherapy (CP) is used in cystic fibrosis (CF) even if there is no robust scientific evidence of a beneficial effect. We investigated the effects of a training with a specific device (SpiroTiger) in a group of CF patients. This device, developed for respiratory training through maximal inspirations and espirations without hypocarbia, may improve respiratory function and mucus clearance. Patients where instructed and trained by a physiotherapist with individualized settings of training parameters. METHODS: Twenty-four patients were enrolled in an open-label 1 year observational study. Baseline and post intervention measurements were determined by lung function (FVC, FEV1, FEF 25-75), patients' opinions on physiotherapy (questionnaires), need for antibiotic treatment (clinical follow-up and records) and perception of physical fitness (questionnaires) in the year before and in the year of intervention. Adherence to physiotherapy was monitored by means of a specific device software. RESULTS: Increased lung function (FEV1 p<0.01), perception of physical fitness (p<0.001) and a reduction in the need for intravenous antibiotic treatment (p<0.001) were reported. Adherence to treatment was good/acceptable in 92% of patients. CONCLUSIONS: This study shows an association between training through a specific device and improved lung function. Further trials are needed to confirm this report.

Deep sedation with propofol for upper gastrointestinal endoscopy in children, administered by specially trained pediatricians: a prospective case series with emphasis on side effects.

BACKGROUND AND STUDY AIMS: The need to administer procedural sedation to children has increased in recent years, as has experience in this field among nonanesthesiologists. Using propofol makes it easier to achieve sufficiently deep sedation. There is a considerable literature on the administration of propofol by nonanesthesiologists for gastroscopy in adults, but very few data are available on this issue in children. The aim of the present study was to assess the safety and efficacy of procedural sedation with propofol for gastroscopy in a pediatric ward with trained personnel and monitoring facilities. PATIENTS AND METHODS: A training protocol was developed to educate nurses and residents. Children requiring gastroscopy were included in the study prospectively and underwent procedural sedation with propofol administered by nonanesthesiologists. RESULTS: A total of 811 upper gastrointestinal endoscopies were carried out with procedural sedation. Sedation was achieved in all procedures, and all but three (0.4%) were conducted successfully. None of the patients required intubation. Stridor with signs of upper airway obstruction occurred in 14 of the 811 procedures (1.7%). Laryngoscopy was required to manage difficulties in introducing the gastroscope in 16 of the 811 procedures (2.0%). Major desaturation requiring a short course of ventilation occurred in six procedures (0.7%), and transient desaturation that resolved spontaneously occurred in 97 of the procedures (12%). CONCLUSIONS: Administration of propofol by nonanesthesiologists for gastroscopy examinations in children was successful in this study, but was associated with a small risk of potentially severe complications. Although the residents were generally able to administer procedural sedation alone, constant and immediate availability of anesthesiological support continues to be mandatory.

Pretreatment with intravenous ketamine reduces propofol injection pain.

BACKGROUND: Paediatric procedural sedation using propofol has been shown to be safe and effective and is widely used. Pain at the injection site is a frequent complaint and can be particularly distressing for children, especially for those undergoing repeated procedures. Ketamine has analgesic properties and can diminish the incidence of propofol infusion pain in adults. The aim of the study was to investigate whether pretreatment with ketamine would reduce infusion line pain in propofol sedation in children. METHODS: We performed a prospective, randomized, double-blind trial in a paediatric sedation unit of a tertiary referral teaching hospital. A total of 122 children admitted for gastroscopy were randomly allocated into two groups. Group 1 received atropine and ketamine before propofol infusion. Group 2 received atropine, normal saline solution, and a mixture of propofol with lidocaine. The main outcome measure evaluated was pain associated with the infusion and secondary outcome measures were mean medium arterial pressure decrease and desaturation. RESULTS: The incidence of pain of the infusion was significantly lower in patients pretreated with ketamine (8% vs 37%, P = 0.0001). CONCLUSIONS: Pretreatment with ketamine (0.5 mg.kg-1) is very effective in preventing propofol infusion pain.

Case report: Salmonella panama osteomyelitis in a Ghanaian child with sickle cell disease.

Sickle cell disease is a rare condition in italian patients and even rarer are its complications, in particular Salmonella osteomyelitis. We describe a case of a Ghanaian child with sickle cell disease who developed osteomyelitis due to Salmonella panama, treated successfully with surgical debridement, followed by a prolonged period of specific antibiotic therapy.

[Polyorchidism: 2 case reports]. / Poliorchidismo: descrizione di due casi.

Polyorchidism is a rare anomaly with approximately 70 cases reported in literature. The exact explanation for the production of polyorchidism is not known, although several theories have been proposed, including anomalous appropriation of cells, initial longitudinal duplication of the genital ridge and transverse division of the genital ridge, either through some local accident of development of peritoneal bands. A functional classification based upon the embryogenic development is provided. Type I: the supernumerary testis lacks an epididymis and vas. The split-off part of the primordial gonad does not communicate with the mesonephric tubules from which the epididymis develops. Type II: the supernumerary testis is linked to the regular testis by a common epididymis and shares a common vas with it. The division of the genital ridge occurs in the region where the primordial gonads are attached to the mesonephric ducts, although the latter are not divided (incomplete division). Type III: the supernumerary testis has its own epididymis but shares the vas with the regular testis. This variant results from a complete transverse division of the genital ridge. In the majority of the reported cases, the patients are asymptomatic and have painless groin or testicular masses. Approximately 50% occur as maldescent or cryptorchidism, and about 30% are associated with indirect hernia. The remaining 20% are discovered variously in relation to torsion, or are associated with hydrocele, epididymitis, varicocele or infertility. Moreover, since there is a 20 to 40 fold increase in testicular malignancy in patients with cryptorchidism compared with the normal testis, tumours of the supernumerary testicles are not unusual. We reported two cases of polyorchidism: the first patient is probably a longitudinal division of the genital ridge and the second is a completely duplication of the primordial gonads. The patients described vague, intermittent, testicular pain. Physical examination and the scrotal sonography and magnetic resonance revealed in the first patient a supernumerary testis in the right scrotal space and in the second a bilateral double testis. In conclusion we think that in the absence of any concomitant disorder and if testicular tumor can be ruled out by ultrasonography and magnetic resonance imaging, surgical exploration with biopsy is unnecessary.

Coeliac disease, folic acid deficiency and epilepsy with cerebral calcifications.

Two cases of focal occipital epilepsy with cerebral calcifications poorly responsive to antiepileptic treatment are described. In both cases coeliac disease was diagnosed and folic acid deficiency documented. A gluten-free diet and a brief supplementation with folic acid lead to a complete EEG and clinical normalization in one case and to a significant improvement of EEG and seizure control in the other.

[Radiological assessment of Crohn disease]. / Bilancio radiologico della malattia di Crohn.

Fifty-eight consecutive cases of patients affected by Crohn's disease, with ileum (23/58), colon (10/58) and ileo-colic (25/58) involvement were studied. A good overall sensitivity was reached by the radiological procedures employed (barium meal, barium enema, enteroclysis). Enteroclysis is proposed as a second-step method for the study of ileum involvement, because it provides a quite precise assessment of disease stage and extent. Some criteria for a rational use of current radiological procedures in the follow-up of both surgically and medically treated patients are proposed. Moreover it is suggested that better coordination of anatomo-radiological and clinical aspects could improve the therapeutic approach and prognostic judgement in such cases.

[Autoimmune thyroid pathology. Study and follow-up of pediatric case reports]. / Patologia tiroidea autoimmune. Studio e follow-up di una casistica pediatrica.

Eight children with Graves' disease and five children with Hashimoto's thyroiditis admitted to the Pediatric Department of the University of Trieste in the period 1980 to 1985 have been reviewed. The purpose of this study was to define the clinical course of autoimmune thyroid diseases and to evaluate the frequency of HLA haplotypes and immunological abnormalities in the affected patients and in their family members. Antithyroid microsomal antibodies were observed in 87.5% of the hyperthyroid patients and in 13.3% of their siblings and parents, in all the patients affected by Hashimoto's thyroiditis and in 18.18% of their first degree relatives. HLA A1-B8 was found to be associated with Graves' disease, HLA B35 was linked to chronic lymphocytic thyroiditis. Using monoclonal antibodies for enumeration of the subsets of T lymphocytes a deficit in suppressor T-cells was demonstrated in subjects affected by autoimmune thyroid diseases as in other immunological disorders.