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The aim of the study was to evaluate the expression of activated mammalian rapamycin (mTOR) and its downstream effectors, phosphorylated p70 ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E-binding protein 1 (4EBP1), in intrahepatic cholangiocarcinomas (ICC), in order to strengthen the rationale for targeted therapy using mTOR inhibitors in patients with ICC. p-mTOR (Ser 2448), p-4EBP1 (Thr 70) and p-p70S6K (Thr 389) were detected in 77 primary ICC tumors by immunohistochemistry. High levels of p-mTOR, p-4EBP1 and p-p70S6K expression were defined in 48.1% (37/77), 50.6% (39/77) and 51.9% (40/77) of all tumors, respectively. No significant correlation was observed between mTOR pathway proteins overexpression with clinicopathological characteristics and patient's prognosis, except that high p-p70S6K expression correlated with the poorly differentiated subtype, and high expression of p-4EBP1 predicted poor prognosis in ICC patients and retained an independent prognostic factor in multivariate analysis. In conclusion, our results showed high prevalence of activation of mTOR pathway in ICC tumors, suggesting that a high proportion of ICC patients might benefit from mTOR pathway targeted therapies. In addition, p-4EBP1 phosphorylation at Thr 70 could be a useful prognostic biomarker for ICC patients.

A 21-year-old man was admitted to our hospital with a high fever of 2-week duration. On physical examination, a grade 3/6 continuous murmur was heard in the left lower sternal border. Laboratory investigations revealed leukocytosis (white blood cell count, 29,800 /mm 3 ; neutrophils, 90%) along with elevated C-reactive protein levels (45.1 mg/dl). Transthoracic echocardiography showed a bicuspid aortic valve (BAV) accompanied by perivalvular abscess; multiple vegetations of the aortic leaflet (14×12 mm) and anterior mitral leaflet (9×8 mm) were found.A ruptured sinus of Valsalva aneurysm (SOVA) originating from the noncoronary sinus and communicating with the right atrium was seen. Color Doppler imaging confirmed the presence of an aorto-right atrial fistula (. Fig. 1). The patient was transferred to the cardiothoracic surgery unit and prepared for surgery. The severely damaged valves were excised and replaced with mechanical valves, and the aneurysm was repaired with a bovine pericardial patch. After surgery, the patient was given intravenous antibiotics for 6 weeks. His postoperative course was uneventful. He was doing well at the 3-month follow-up visit.SOVA is usually congenital, but it can also occur secondary to infection, trauma, and other acquired cardiac diseases [1]. In our case, the patient's initial symptom was fever, followed by breathing difficulties after a few days. Thus, we infer that the aortic perivalvular abscess resulted in a ruptured SOVA. The prognosis of ruptured SOVA is poor and patients usually succumb to acute cardiac failure [2]. Early diagnosis and treatment are generally associated with a good outcome.