ABSTRACT
PURPOSE: Oral appliances (OA) have become the main alternative to positive pressure airway devices (PAP) for the control of obstructive sleep apnea (OSA). Despite literature support, controversies about the mode of action and the effectiveness of these devices persist. The aim of this study was to evaluate the efficacy of modified mandibular advancement devices (MAD) in patients with OSA who failed treatment with MAD and to evaluate the role of the tongue as a factor in patients who failed treatment with MAD. MATERIALS AND METHODS: Patients unable to control the apnea-hypopnea index (AHI) using a MAD were subsequently treated with a modified version that included a tongue trimming accessory. The objective was to stabilize the tongue by preventing it from sliding with the consequent collapse of the upper airway (UA). New polysomnography (PSG) was performed with the modified MAD in place. RESULTS: A total of 20 patients who failed MAD therapy were studied including 15 men (75%) with mean age (± standard deviation) of 58.5 ± 13.1 years and BMI 29.6 ± 5.0 Kg/m2. After installing the tongue trimmer, the number of patients who achieved complete success with the new MAD (AHI < 5) went from 0 to 30% and those who achieved partial success (5 < AHI < 10) went from 0 to 20%. The number of patient responders (AHI reduced by at least 50%) went from 20 to 75%. CONCLUSION: The results suggest that the tongue, even in the presence of a MAD, may be one of the contributing factors for the collapse of the UA and consequent device ineffectiveness. By stabilizing the tongue through the insertion of a tongue trimmer, the MAD became more effective in many cases.
ABSTRACT
O colangiocarcinoma (CCA) é a segunda neoplasia mais maligna do fígado que surge na árvore biliar. O CCA está associado com mau prognóstico e os principais fatores envolvidos em sua patogênese não são bem compreendidos. Os receptores tirosina quinases (RTKs), como o receptor do fator de crescimento epidérmico (EGFR), podem mediar as vias de sinalização de cálcio intracelular (Ca 2+ ), via inositol 1,4,5-trifosfato (InsP3). Eles ativam os receptores 1,4,5-trifosfato (ITPRs) e regulam o crescimento tumoral. ITPR isoforma 3 é o principal canal de liberação intracelular de Ca 2+ em colangiócitos. Os efeitos do Ca 2+ intracelular, por sua vez são mediados por proteínas de ligação de cálcio, como calmodulina e proteína A4 de ligação de cálcio S100 (S100A4). No entanto, o significado clínico patológico e biológico de EGFR, ITPR3 e S100A4 no CCA permanece obscuro. Assim, o presente trabalho investiga a imuno exprepressão dessas três proteínas em 59 pacientes diagnosticados com CCA, submetidos a tratamento cirúrgico curativo e correlaciona os dados com características clínico-patológicas e sobrevida. A alta expressão de ITPR3 foi correlacionada com os níveis de CA 19-9, estágio TNM e metástases em linfonodos (N). Além disso, a expressão de ITPR3 foi aumentada em CCA distal em comparação com ductos biliares de controle e CCAs intra-hepáticos e peri-hilares. Os escores clínicos ITPR3 e S100A4 foram significativamente correlacionados. Em resumo, a super expressão de ITPR3 pode contribuir para a progressão da CCA e pode representar um potencial alvo terapêutico. Palavras-chave: ITPRs; ITPR3; S100A4; Colangiocarcinoma; Fígado; Câncer
Cholangiocarcinoma (CCA) is the second most malignant neoplasm in the liver that arises from the biliary tree. CCA is associated with a poor prognosis, and the key players involved in its pathogenesis are still not well understood. Receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR), can mediate intracellular calcium (Ca2+) signaling pathways via inositol 1,4,5trisphosphate (InsP3), activating inositol 1,4,5-trisphosphate receptors (ITPRs) and regulating tumor growth. ITPR isoform 3 (ITPR3) is the main intracellular Ca2+ release channel in cholangiocytes. The effects of intracellular Ca2+ are mediated by calciumbinding proteins such as Calmodulin and S100 calcium-binding protein A4 (S100A4). However, the clinicopathological and biological significance of EGFR, ITPR3 and S100A4 in CCA remains unclear. Thus, the present work investigates the immunoexpression of these three proteins in 59 CCAs from patients who underwent curative surgical treatment and correlates the data with clinicopathological features and survival. High ITPR3 expression was correlated with CA 19-9 levels, TNM stage and lymph node metastasis (N). Furthermore, ITPR3 expression was increased in distal CCA compared to control bile ducts and intrahepatic and perihilar CCAs. In summary, ITPR3 overexpression could contribute to CCA progression and it may represent a potential therapeutic target.
