No abstract

Background/AimsThe efficacy of surveillance for esophageal squamous cell neoplasia (ESCN) in patients with head and neck squamous cell carcinoma (HNSCC) remains controversial. Our study aimed to provide clinical data concerning the necessity of surveillance for detecting early ESCN in patients with HNSCC.MethodsWe retrospectively reviewed the data from 714 patients who were pathologically confirmed as having HNSCC (n=236 oral cavity cancers, 137 oropharyngeal cancers, 87 hypopharyngeal cancers, and 254 laryngeal cancers).ResultsOf 714 patients, during a median follow-up of 31 months, 48 ESCNs (37 synchronous and 11 metachronous) were detected in 36 patients (5%). Fifteen synchronous lesions (40.3%) were early ESCN, whereas nine metachronous lesions (81.8%) were early ESCN. The 3-year survival rates of HNSCC only and HNSCC combined with ESCN were 71.2% and 48.2%, respectively (p<0.001). Among 36 patients with ESCN, the 3-year survival rates for early and advanced ESCN were 77.7% and 21.7%, respectively (p=0.01). In the multivariate analysis, alcohol consumption and hypopharyngeal cancer were significant factors associated with the development of ESCN.ConclusionsHN-SCC patients with early ESCN were similar in prognosis with patients without ESCN, in contrast to patients with advanced ESCN. Therefore, surveillance for the early detection of ESCN in patients with HNSCC, especially in alcohol drinkers and those with hypopharyngeal cancer, is warranted.

BackgroundAmbroxol (ABX) has been suggested as an augmentative pharmacological agent for neuronopathic Gaucher disease (nGD). This study assessed the long-term safety and efficacy of combined therapy with high-dose ABX and enzyme replacement therapy (ERT) in nGD.MethodsABX+ERT therapy was administered for 4.5 years in four patients with nGD. ABX was initiated at a dose of 1.5 mg/kg/day, and the dose was escalated up to 27 mg/kg/day. The target plasma level was 10 µmol/L or less. The changes in glucocerebrosidase activity, biochemical, safety and neurocognitive findings were assessed.ResultsEnhanced residual GCcase activity was observed in all patients, as evidenced in both in vitro and in vivo studies. During the first 2 years of study with ABX (up to 21 mg/kg/day), mean seizure frequencies and neurocognitive function worsened. After ABX dosage was increased up to 27 mg/kg/day of ABX, its trough plasma concentration was 3.2–8.8 µmol/L. Drug-to-drug interaction, especially with antiepileptic drug significantly affected the pharmacokinetic parameters of ABX. Importantly, at 27 mg/kg/day of ABX, the seizure frequencies markedly decreased from the baseline, and the neurocognitive function was improved. In addition, Lyso-Gb1, a biomarker for the severity and progression of GD, was normalised in all patients. High-dose ABX was well-tolerated with no severe adverse events.ConclusionsLong-term treatment with high-dose ABX+ERT was safe and might help to arrest the progression of the neurological manifestations in GD.