Long-term survival after head and neck cancer surgery with immediate free flap reconstruction.

BACKGROUND: Head and neck cancer is one of the most frequent cancers worldwide. A combination treatment including surgery is known to have a better survival rate than exclusive radiotherapy-chemotherapy. In extreme cases of non-metastatic patients who have voluminous tumor, or complex location, surgery with immediate reconstruction by free flap could be an option to improve long term survival. PURPOSE: To share experience of long-term survival of patients with head and neck cancer who underwent oncologic surgery with immediate free flap reconstruction, and to analyze influencing factors. METHODS: All consecutive patients treated with free flaps for reconstruction of extensive defects after resection of head and neck cancer in our center (Nancy, France) were retrieved from the hospital database. Data was recorded in a systematic way. Bivariate and multivariate Cox proportional hazards models were used for statistical analysis. RESULTS: Between 1997 and December 2007, 70 patients underwent surgical resection of head and neck tumor with free flap reconstruction. 11 patients were excluded because of missing data. Follow-up time was 7.4 years, IQR from 4.3 to 11.3. Overall survival was 53.8%, 95% CI [39.9%; 65.8%] at 5 years and 38.6% [24.8%; 52.3%] at 10 years. Age>60 years at the surgery HR 2,373 (1,143; 4,927) and TNM score 3-4 HR 2,524 (1,093; 5,828) were statistically associated to a lesser survival rate. CONCLUSION: The ability to successfully and safely perform free flaps increases treatment options for patients with advanced head and neck cancer in a selected population. it seems worthwhile to perform these microvascular reconstructions.

Refractory lymphorrhoea of the neck treated with etilefrine.

BACKGROUND: Intraoperative injury of the thoracic duct is an uncommon complication of head and neck surgery, which is difficult to manage and associated with serious consequences. We report a case of lymphorrhoea of the neck refractory to all the usual treatments that resolved in response to a treatment strategy described in thoracic and visceral surgery: use of a sympathomimetic drug, etilefrine. To our knowledge and after review of the literature, this is the first reported case of lymphorrhoea of the neck treated by etilefrine. CASE REPORT: Our patient presented massive lymphatic fluid leakage following left neck dissection as part of the management of oropharyngeal cancer with lymph node metastases. The treatments usually proposed, such as intraoperative repair and appropriate dietary and drug management, were not effective, resulting in multiple, severe complications. After evaluation of the benefit-risk balance, treatment with etilefrine was introduced at the dosages proposed in the literature for the management of chylothorax. This treatment allowed complete resolution of the lymphatic fluid leak after one week. DISCUSSION: Etilefrine can therefore be added to the treatment options for the management of lymphatic fluid leaks refractory to the usual treatments.

Ethanol oxidation into acetaldehyde by 16 recombinant human cytochrome P450 isoforms: role of CYP2C isoforms in human liver microsomes.

The involvement of cytochromes P450 (CYPs) in the oxidation of ethanol into acetaldehyde was investigated by using 16 recombinant human CYP isoforms. Apparent K(m) and V(m) were determined for CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, CYP2C8, CYP2C9*1, CYP2C9*2, CYP2C9*3, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP2J2, CYP3A4 and CYP4A11. All of the tested CYPs, except CYP2A6 and CYP2C18, metabolized ethanol into significant amounts of acetaldehyde and displayed K(m) values around 10mM. The significant correlation found between ethanol oxidation and CYP2E1, CYP3A4 and CYP1A2 catalytic activities in a panel of human liver microsomes confirmed the strong implication of these CYPs in ethanol metabolism. The contribution of CYP2C isoforms which are the most abundant in the liver after CYP3A4, was studied using selective inhibitors either with recombinant CYP2C isoforms or in human liver microsomes. Tienilic acid (100 microM) and ticlopidine (20 microM), mechanism-based inhibitors of CYP2C9 and CYP2C19, respectively, decreased ethanol oxidation by 8+/-1.2% and 7.6+/-1.6% in human liver microsomal samples while selective inhibitors of CYP2E1 (DEDTC 100 microM), CYP3A4 (TAO 50 microM) and CYP1A2 (furafylline 25 microM) decreased it by 11.9+/-2.1%, 19.8+/-1.9% and 16.3+/-3.9%, respectively. As ethanol can be metabolized by most of CYPs, it helps to explain or predict alcohol-xenobiotics interactions which are of high importance in medical prescription.