Lysyl oxidase-like 2 (Loxl2) interacts with and stabilizes Snai1 transcription factor, promoting epithelial-mesenchymal transition. Either Loxl2 or Snai1 knock-down blocks tumor growth and induces differentiation, but the specific role of each factor in tumor progression is still unknown. Comparison of the gene expression profiles of the squamous cell carcinoma cell line HaCa4 after knocking-down Loxl2 or Snai1 revealed that a subset of epidermal differentiation genes was specifically upregulated in Loxl2-silenced cells. In agreement, although both Loxl2-and Snai1-knockdown cells showed reduced in vivo invasion, only Loxl2-silenced cells exhibited a skin-like epidermal differentiation program. In addition, we show that expression of Loxl2 and Snai1 correlates with malignant progression in a two-stage mouse skin carcinogenesis model. Furthermore, we found that increased expression of both LOXL2 and SNAI1 correlates with local recurrence in a cohort of 256 human laryngeal squamous cell carcinomas. We describe for the first time that high levels of LOXL2 are associated with decreased overall and disease-free survival in laryngeal squamous cell carcinomas, lung squamous cell carcinoma, and lymph node-negative (N 0 ) breast adenocarcinomas. Altogether, our results show that LOXL2 can be used as a new poor prognosis indicator in human squamous cell carcinomas promoting malignant transformation by both SNAI1-dependent and SNAI1-independent pathways. [Cancer Res 2008;68(12):4541-50]
To identify potential risk factors related to complications after thyroidectomy, a study was designed that included 675 patients. Recurrent laryngeal nerve (RLN) paralysis, hypocalcemia, serohematoma, wound infection, and postoperative hemorrhage were evaluated. The rate of paralysis of the RLN was calculated on nerves at risk for hypocalcemia (n = 890) in patients undergoing bilateral procedures or unilateral procedures if they had previously undergone a contralateral operation (n = 321). Multivariate analysis was used to identify the relationships between the variables included in the study. All statistical tests received the same level of significance of 0.05. Permanent hypocalcemia occurred in 2.2% of the patients, whereas unilateral paralysis of the RLN developed in 0.9%. Mortality was 0.1% in this series. The RLN paralysis had a significant relationship with preoperative diagnosis of malignancy (P < 0.03). Likewise, hypocalcemia was related to sex and surgical procedure (P < 0.03). Serohematoma was linked with age (P < 0.001), and hemorrhage was associated with previous radiation of the neck (P < 0.03).
A retrospective study was done to assess the incidence and factors associated with neurological complications in patients who have undergone a functional neck dissection (FND). Four hundred forty-two epidermoid cancer patients operated on from January 1984 to December 2002 were included in the study. Clinical parameters, neurological sequelae, and other complications were evaluated in all cases. The incidence of neural damage was calculated on the nerves at risk (n =714). Paralysis of the 11th nerve occurred in 12 cases (1.68%). A lesion of the marginal branch of the 7th cranial nerve was observed in nine cases (1.26%). Bernard-Horner's syndrome and hypoglossal nerve paralysis were noted in four and three cases (0.56 and 0.42%), respectively. Thus, the incidence of neurological sequelae after FND is low. Neurological complications were not associated with either clinical parameters or non-neurological complications (P >0.05). None of the factors studied can predict the appearance of neural problems in the postoperative period.
In a prospective, controlled, and randomized study, we compared the outcome of 101 Bell's palsy patients treated with acyclovir (54 patients) or prednisone (47 patients). The acyclovir dosage was 2400 mg (800 mg three times a day) for 10 days, and prednisone was given as a single daily dose of 1 mg/kg of body weight for 10 days and tapered to 0 over the next 6 days. Minimum follow-up was 3 months in all patients. Patients in the prednisone group had better clinical recovery than those treated with acyclovir. Less degree of neural degeneration was observed in the prednisone group compared with acyclovir patients. The incidence of sequelae was the same in both groups. According to these results, in a 10-day treatment cycle acyclovir given 800 mg three times is not as useful as prednisone given 1 mg/kg of body weight once a day in patients with idiopathic facial nerve paralysis.
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