p16 (INK4a) has clinicopathological and prognostic impact on oropharynx and larynx squamous cell carcinoma

CDKN2A encodes proteins such as p16 (INK4a), which negatively regulate the cell-cycle. Molecular genetic studies have revealed that deletions in CDKN2A occur frequently in cancer. Although p16 (INK4a) may be involved in tumor progression, the clinical impact and prognostic implications in head and neck squamous cell carcinoma (HNSCC) are controversial. The objective of this study was to evaluate the frequency of the immunohistochemical expression of p16 (INK4a) in 40 oropharynx and 35 larynx from HNSCC patients treated in a single institution and followed-up at least for 10 years in order to explore potential associations with clinicopathological outcomes and prognostic implications. Forty cases (53.3%) were positive for p16 (INK4a) and this expression was more intense in non-smoking patients (P = 0.050), whose tumors showed negative vascular embolization (P = 0.018), negative lymphatic permeation (P = 0.002), and clear surgical margins (P = 0.050). Importantly, on the basis of negative p16 (INK4a) expression, it was possible to predict a probability of lower survival (P = 0.055) as well as tumors presenting lymph node metastasis (P = 0.050) and capsular rupture (P = 0.0010). Furthermore, increased risk of recurrence was observed in tumors presenting capsular rupture (P = 0.0083). Taken together, the alteration in p16 (INK4a) appears to be a common event in patients with oropharynx and larynx squamous cell carcinoma and the negative expression of this protein correlated with poor prognosis.

Long term results of percutaneous transluminal valvuloplasty in patients with valvular aortic stenosis.

The results of percutaneous balloon aortic valvuloplasty (PBAV) in 62 consecutive patients with valvular aortic stenosis are reported. The age of the patients ranged from 11 months to 72 years (mean 28 +/- 12 years). Hemodynamically successful dilatation was achieved in 58 out of 62 patients. This was associated with marked clinical improvement in these patients. The left ventricular aortic peak to peak gradient decreased from 96.67 +/- 38.4 to 28.14 +/- 26.5mmHg (p < 0.01). There were no deaths during the procedure. Only one patient died in the hospital during the same admission. There was an increase in aortic regurgitation (AR) by at least one grade in 25 (40.3%) patients. Femoral arterial thrombosis was seen in 9/62 patients, 5 of them requiring surgical intervention. Follow up was available in 28 (45.1%) patients over a period of 2-15 months (mean 9 +/- 3 months). Two patients died during the follow up period. Doppler evaluation of gradients was done in all 28 patients with 15 consenting to undergo repeat cardiac catheterisation. Although hemodynamically the restenosis rate was 35.7% (10/28), only 2 of these patients showed symptomatic deterioration. The success of dilatation and restenosis rate were independent of the etiology of aortic stenosis, presence of calcification and the number of balloons used. This study demonstrates that PBAV is feasible in valvular aortic stenosis at low risk and is able to produce significant clinical and hemodynamic improvement in most cases with a restenosis rate of 35.7% at a follow up period of 9 +/- 3 months.