Long-term morbidity and mortality in 2-year hepatoblastoma survivors treated with SIOPEL risk-adapted strategies.

BACKGROUND AND AIMS: Prognosis of hepatoblastoma patients has increased with cisplatin-based chemotherapy and high-quality resection including liver transplant. Consequently current risk-adapted therapeutic strategy aims to reduce long-term side effects in patients with standard risk disease. METHODS: We report long-term mortality and morbidity data concerning 151 2-year hepatoblastoma survivors treated with SIOPEL risk-adapted strategies (sex-ratio M/F = 1.6, median age at diagnosis = 2.6 years [range 0-17.7], median year at diagnosis = 2008 [1994-2017]). Fifty-three patients had loco-regional risk factors VPEFR, 12 were PRETEXT-IV and 30 were metastatic. All received cisplatin and 84 anthracyclines. Twelve had liver transplant. To assess hearing, renal and cardiac functions, audiograms were performed in 116/151 patients (76.8%), glomerular filtration rate in 113/151 (74.8%) and cardiac ultrasound in 65/84 (77.4%) anthracycline-exposed patients. RESULTS: With a median follow-up of 9.4 years (range 2.1-25.8), four late relapses, one second malignancy (Acute Myeloid Leukemia AML-M5) and two deaths (one from hepatoblastoma, one from AML) occurred. The 10-years event free survival and overall survival probabilities were 95.5% (95% CI 91.9-99.1) and 98.7% (95% CI 96.8-100), respectively. Sixty-eight non-oncologic health-events included 57 cases of hearing loss (including 25 Brock 3-4), three liver cirrhosis, three pre-operative portal cavernoma, two focal nodular hyperplasia, two grade-1 chronic kidney diseases and one asymptomatic cardiac dysfunction were reported. Ototoxicity was significantly associated with cisplatin cumulative dose (OR = 2.07, 95% CI 1.32-3.24, p = 0.001) and carboplatin exposure (OR = 3.14, 95% CI 1.30-7.58, p = 0.01) in multivariable analysis adjusted for sex and age at diagnosis. CONCLUSIONS: With current risk-adapted strategies, hepatoblastoma is a highly curable disease, with very rare relapses, and few late effects except hearing loss which remains a serious condition in these very young patients.

Regional surveillance of emergency-department visits for outpatient adverse drug events.

AIMS: To determine the (1) incidence of adverse drug events (ADEs) in 10 emergency department (EDs) of general hospitals in the Regione Campania (southern Italy), (2) rate of ADE-related hospital admissions, (3) drug classes most frequently involved, and (4) the types of ADEs and their frequency. METHODS: We performed a cohort study of all patients attending the EDs. This study was carried out in two observational periods of 10 days each in 10 EDs. Demographic, clinical, and pharmacological data about all patients admitted to EDs were collected by trained and qualified monitors. Records related to ADEs were analyzed and validated by a specific scientific committee. RESULTS: Of 7,861 ED visits, 96 were ADE-related. The incidence of hospitalization was higher in patients who had taken medication than in patients with a negative drug history (24.9 vs. 16.4%). ADEs were significantly more frequent in women. Patients aged between 60 and 69 years and between 30 and 39 years were significantly more likely to experience an ADE. Serious ADEs were identified in 20 ED visits (20.8% of total sample). Antibiotics, NSAIDs, and agents acting on the renin-angiotensin system were the drugs most often involved in ADEs. In multivariate analyses, the adjusted odds ratio was 3.4 (95% CI: 1.07-2.84) for patients taking NSAIDs, 4.78 (95% CI: 2.26-10.12) for those taking beta(2)-adrenergic-receptor agonists, and 6.20 (95%CI: 2.74-14.06) for those taking beta-lactam antibiotics. CONCLUSION: This study shows that ADEs are an important problem in industrialized countries. Moreover, it shows that ADEs affect hospital admission rates and reinforces the importance of drug-induced disease as a public health problem.