Maria Grazia Scuderi

Altered 'active' antireflux mechanism in primary vesico-ureteric reflux: a morphological and manometric study

To immunolocate c‐kit‐positive interstitial cells of Cajal (ICCs, known to be responsible for pacemaker activity in human ureters, coordinating ureteric motility) in the intramural ureter of patients with different grades of vesico‐ureteric reflux (VUR), to assess the ureteric histology and correlate these findings with manometric patterns.

Symptomatic hypocalcemia in an epileptic child treated with valproic acid plus lamotrigine: a case report

IntroductionAn epileptic child had been long treated with valproic acid and lamotrigine. After a few years of treatment, he manifested severe clinical signs of hypocalcemia. We retain that valproic acid could have caused such metabolic dysfunction.Case presentationWe report here the involvement of valproic acid in symptomatic hypocalcemia in an 11-year-old epileptic white patient in treatment with valproic acid and lamotrigine. During the treatment the patient developed hypocalcemia associated with high plasma levels of valproic acid, parathyroid hormone and alkaline phosphatase, indicating increased bone turnover. Plasma levels of Vitamin D were normal. Plasma calcium values significantly correlated with valproic acid haematic levels; reduction of valproic acid dose was accompanied by prompt normalization of calcemia.The specific mechanism through which valproic acid causes hypocalcemia is unknown, although the relationship between valproic acid dose and haematic levels of calcium appears very likely.ConclusionsIt seems necessary, during long term therapy with valproic acid, to monitor plasma calcium and alkaline phosphatase plasma levels. Also, these patients should undergo treatment and perhaps prescribe vitamin D and calcium treatment.

Persistence in Therapy With Risperidone and Aripiprazole in Pediatric Outpatients: A 2-Year Naturalistic Comparison.

OBJECTIVE The practical effectiveness of second-generation antipsychotics in children and adolescents is an understudied issue. It is a crucial area of study, though, because such patients are often treated for long-lasting disorders. METHODS We carried out a 24-month (March 2012-March 2014) observational study on an unselected population of pediatric outpatients treated with risperidone, aripiprazole, olanzapine, or quetiapine aiming to (1) describe drug use, (2) compare post hoc the discontinuation rates due to specific causes and dose adjustments by Kaplan-Meier analyses between drugs, and (3) analyze predictors influencing these outcomes by Cox multivariate models. RESULTS Among 184 pediatric patients, 77% patients were prescribed risperidone, and 18% were prescribed aripiprazole. Olanzapine or quetiapine were scantly used; therefore, they were excluded from analyses. Risperidone was prevalent in younger, male patients with disruptive behavioral disorders; aripiprazole, in patients with tic disorders. Overall, discontinuations occurred mostly in the first 6 months, and, at 24 months, the discontinuation numbers were similar between users of risperidone and aripiprazole (41.5% vs 39.4%). In univariate analyses, dose reduction was higher for aripiprazole (P = .033). Multivariate analyses yielded the following predictors: for all-cause discontinuation, baseline severity (hazard ratio [HR] = 1.48, P = .001) and dose increase (HR = 3.55, P = .001); for patient-decided discontinuation, dose change (increase: HR = 6.43, P = .004; reduction: HR = 7.89, P = .049) and the presence of concomitant drugs (HR = 4.03, P = .034), while autistic patients discontinued less (HR = 0.23, P = .050); for clinician-decided discontinuation due to adverse drug reactions, baseline severity (HR = 1.96, P = .005) and dose increase (HR = 5.09, P = .016); for clinician-decided discontinuation due to inefficacy, baseline severity (HR = 2.88, P = .014) and the use of aripiprazole (HR = 5.55, P = .013); for dose increase, none; for dose reduction, the occurrence of adverse drug reactions (HR = 4.74, P = .046), while dose reduction was less probable in autistic patients (HR = 0.22, P = .042). CONCLUSIONS The findings of this study show a similarity between the overall effectiveness of risperidone and aripiprazole in a real-life pediatric outpatient setting.

Evaluation of Neoadjuvant Chemotherapy Effects on Liver Parenchyma in Resected Pediatric Malignancies

Neoadjuvant chemotherapy for colorectal liver metastases in adults is responsible for chemotherapy-associated liver injury (CALI), characterized by steatosis, steatohepatitis, and sinusoidal obstruction syndrome. These alterations cause delayed operation to reduce the risk of hemorrhage, portal hypertension, and hepatic failure. Children with hepatic malignancies usually receive neoadjuvant chemotherapy prior to surgery. The aim of this study was to evaluate retrospectively whether the CALI occurs in this pediatric population. This study evaluated patients referred since 1996 for hepatic malignancies who received hepatectomy after chemotherapy. Liver resection material was reviewed, in order to investigate the presence of morphological changes compatible with the CALI in the peritumoral hepatic tissue. Twelve patients were recruited. All patients satisfied the inclusion criteria except one who did not receive neoadjuvant chemotherapy. Eleven children underwent surgery 1 month after the last chemotherapy cycle. All are alive disease-free. Histological examination of specimen revealed only mild changes such as diffuse swelling of hepatocytes and focal, mild portal inflammation. Severe hepatic changes such as steatosis, necrosis, or fibrosis were not identified. CALI-related morphological changes were not found in our patients. The absence of the CALI could be attributed to the younger age of patients (possible different response to stress) and/or to the different chemotherapy schedules compared to those in use for adults patients.

YKL-40 as marker of severe lung disease in cystic fibrosis patients

BACKGROUND YKL-40 is a chitinase-like protein present in serum of healthy subjects and its levels are increased in several human inflammatory diseases. The aim of this study was to evaluate the levels of both serum and sputum YKL-40 in cystic fibrosis (CF) patients. METHODS Serum and sputum YKL-40 levels were measured in a cohort of twenty-eight patients with a diagnosis of CF and twenty healthy controls. RESULTS Serum YKL-40 levels were significantly higher in CF patients (88.8±56.7 vs 18.6±2.9ng/ml, P<0.001), as well as sputum YKL-40 levels (138.5±132.7 vs 28.2±24.34, P<0.001) than in healthy controls. Serum YKL-40 levels were closely related to YKL-40 levels assessed in sputum samples (r=0.71; P<0.01). CONCLUSIONS YKL-40 is elevated in CF patients and is further elevated during severe exacerbations. Longitudinal studies in infant are needed to establish its role in disease pathogenesis.

An unusual case of severe microcytic anemia.

To the Editor: A 14-year-old boy presented with pallor and asthenia. Laboratory data showed microcytic anemia (Hemoglobin 6.9 g/dL, erythrocytes 4.56 10/mL, mean corpuscular volume 59 fl, reticulocytes 72 10/L, ferritin 1.4 ng/mL, transferrin saturation 1%), microscopic blood and Helicobacter Pylori in stool, and negative markers for celiac disease. Clarithromycin, amoxicillin, and omeprazole, together with oral iron, were prescribed but the boy discontinued the follow-up. One year later, he returned with abdominal pain, vomiting, diarrhea, difficulty in food intake, and weight loss. During the previous year, he had occasionally followed the prescribed treatment with temporary benefits. Physical examination revealed abdominal distension but no palpable masses. Computerized tomographic scan showed parietal thickening of rectum and sigma with a mass measuring 84 33mm whose wall was highlighted after contrast medium injection while its content was hypodense. Two more masses with the same radiologic features were found between the descending colon and the sigma and at the splenic colon flexure. The mucosa was very thin, almost absent in several points. Owing to the high risk of spontaneous perforation, the patient was operated although radical excision was not feasible. Extended hemicolectomy and right colostomy were performed. Another 5 cm long mass was found in continuity with the duodenum and pancreas but due to its position it was unresectable. Macroscopic examination revealed 2 tumor masses: the largest (5 5 cm), found in the transverse colon, was ulcerative/infiltrating, circumferential, and perforating the intestinal wall; the second mass (5.5 3 cm), found in the sigmoidal colon, was polypoid and caused serosal retraction. Another 10 5 cm subserosal mass proved to be metastatic lymph nodes. Histologic final diagnosis was of synchronous poorly differentiated (G3) adenocarcinomas of large bowel with prevalent mucinous pattern; serosal and lymphatic neoplastic invasion; direct infiltration of a seminal vescicle; metastasis in 16 regional lymph nodes out of 46. Tumor nodes metastasis staging was pT4b N2b. We performed the analysis for the mutation of the K-RAS gene but it was not mutated (wild type). There was no familial history of colorectal cancer. After surgery, the patient’s conditions improved, although on the 10th day he had to be reoperated because of peritoneal signs. A duodenal fistula was found and closed, but the boy eventually died on 22nd day for persistence of bile in peritoneum. Colorectal cancer is extremely rare in patients under 20 years of age, with an incidence of 1 to 2 per million, and the prognosis is unfavorable. In the period 2000/2010, Medline database records approximately 300 cases of colorectal cancer in patients aged from 8 to 19 years. Our case confirms the findings reported in literature. The negative prognosis may be related to various factors. These tumors usually present at an advanced local stage, with a great incidence of unfavorable histologic variants. Moreover, the poor knowledge in the occurrence of colorectal cancer in children contributes to delay its diagnosis. Even though microcytic anemia with evidence of fecal blood loss in children is usually due to other reasons, it is advisable to include colorectal cancer in differential diagnosis.

Molecular events involved in the morphogenesis of multicystic dysplastic kidney.

Introduction: Wnt-1 is capable of inducing metanephric mesenchyme to undergo tubulogenesis. A relationship between the degree of cystogenesis and reduced E-cadherin (E-cad) expression was described. Syndecan-1 (Sdc-1) has a critical role in kidney development. Materials and Methods: Ten multicystic dysplastic kidneys (MCDKs) were stained with hematoxylin and eosin and immunohistochemistry was performed using Wnt-1, E-cad and Sdc-1 antibodies. Eight unaffected kidneys were used as controls. Results: Strong Wnt-1 immunostaining occurred inside cystic/tubular epithelial cells and in blastematous foci. An immunoreaction was observed in glomerular epithelial cells. In controls, just weak cytoplasmic Wnt-1 positivity was seen in tubular epithelial cells. E-cad reaction was negative in MCDKs while strong immunostaining was common in tubular cells of controls. A strong Sdc-1 immunoreaction depicted cystic, tubular and glomerular epithelial cells in MCDKs while Sdc-1 expression documented weak positivity in tubular epithelium alone. Conclusions: Our data are in accordance with an involvement of Wnt-1 in normal nephrogenesis and with its role in altered epithelial differentiation of metanephric mesenchyme in MCDKs. Wnt-1 signal may function to suppress E-cad expression, a predisposing event for cystogenesis. High expression of Sdc-1 in tubular/cystic epithelial cells of MCDKs might alter the normal transition of stages of the developmental process and modify the anion charge of the glomerular barrier.

Guidelines of the Italian Society of Videosurgery in Infancy for the minimally invasive treatment of the esophageal atresia

Not available.

Guidelines of the Italian Society of Videosurgery in Infancy for the minimally invasive treatment of pediatric nephrectomy and partial nephrectomy

Not available.

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

Not available.