State of the art and perspectives in pediatric hepatocellular carcinoma.

Hepatoblastoma (HB) and pediatric hepatocellular carcinoma (HCC) are rare primary malignant liver cancers in children and young adults. HB is the most common and accounts for about 70 % cases; it is usually diagnosed during the first 3 years of life. Instead, pediatric HCC is uncommon, and it is associated with a poor prognosis. Overall, the prognosis of pediatric HCC is dismal with 5-year event-free survival of <30 % as compared to >80 % for HB. Surgery approaches, either resection or transplant, remain the best chance for the cure of pediatric HCC. However, chemotherapy can be helpful as an adjuvant or neoadjuvant treatment. International groups have done trials in pediatric HCC with a chemotherapy regimen, based on cisplatin and doxorubicin (PLADO) as for HB, but the efficacy is limited. Sorafenib, a multi-kinase inhibitor, following positive results in adults and in a pilot study in children, is now tested in conjunction with chemotherapy in the PHITT phase III clinical trial. Some studies have been exploring the genetic profiles of patients to find biological hallmarks that determine the aggressiveness of pediatric HCC. Pathways involved in growth and differentiation are dysregulated and as demonstrated in HB and adult HCC, an important role of the Wnt/CTNNB1 pathway in the pathogenesis of pediatric HCC is also emerging. An extended molecular analysis of tumor samples could give information about pathways as possible targets of biological and immunotherapeutic agents bringing new pharmacological options for the treatment of pediatric HCC.

Spontaneous Dissemination in Neighboring Provinces of DKA Prevention Campaign Successfully Launched in Nineties in Parma's Province.

AIM: to investigate how much effectiveness of the historical campaign of DKA prevention at T1D diagnosis has survived in Parma's province where this was launched in Nineties, and how much it has spontaneously spread in the neighboring provinces. METHOD: children aged 6-14 years with newly diagnosed TID coming from province of Parma (Group 1) and from two other nearby provinces (Group 2)  were investigated. Clinical and laboratory data were retrospectively collected from medical files of each patient and included age, gender, capillary pH, serum bicarbonate, 3-beta-hydroxybutyrate (3HB), glycated hemoglobin (HbA1c) at the time of admittance from 1st January 2012 and 31 December 2016. RESULTS: no DKA condition was globally found in 25/36 patients (69.4%): 16/17  and 9/19 patients  belonged to Group 1 and 2 respectively (p=0.002). Mild or moderate DKA was reported in 5.9% patients of Group 1 and in 47.31%  (p=0.005) patients from Group 2. Severe DKA was observed in only 1 child from Group 2. Normal 3-beta-hydroxybutyrate (3HB) serum levels was reported in the 25 patients without DKA at diabetes diagnosis. Duration of hyperglycemia-related symptoms before overt T1D diagnosis was shorter (4.6±2.5 days) in patients with 3HB levels <1 mmol/dl  than in those with 3HB levels exceeding  1 mmol/dl (9.6±4.2 days, p< 0.0001). HbA1c values were on overage lower in patients without DKA (9.9±1.2%) than in patients with DKA at diabetes diagnosis (13.60±1.3%; p< 0,001). CONCLUSION: 1) the campaign for DKA prevention, launched  in Nineties and renewed at beginning of Twenties in Parma's province,  continues to be effective in the same province after several years; 2) in the two control provinces despite no information campaign being officially promoted in loco, an unexpected decrease in severe DKA incidence as well a shorter latency before overt T1D diagnosis were  observed in the same  period.