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Microvascular free tissue transfer in head and neck reconstruction requires suitable recipient vessels which are frequently compromised by prior surgery or radiotherapy to the neck. This article details a new technique of arterial free flap pedicle anastomosis to the internal carotid artery in a vessel-depleted neck. A 63-year-old female was referred because of recurrence of squamous cell carcinoma of the tongue, which involved the left-sided tongue base and pharynx with circumferential involvement of the homolateral external carotid artery. This artery and its branches were excluded as potential recipients. To close the defect after tumor excision, a free vertical rectus abdominis muscle arterial flap pedicle was anastomosed to the homolateral internal carotid artery with the help of a Pruitt-Inahara outlying carotid shunt. The venous anastomosis was performed to the internal jugular vein. The VRAM flap survived without complications. This procedure is to be considered an alternative rescue technique for salvage reconstruction in vessel depleted necks., (Copyright © 2011 Wiley-Liss, Inc.)

Epidermal growth factor receptor (EGFR) overexpression is an unfavorable prognostic marker in laryngeal squamous cell carcinoma (SCC). EGFR stimulates cyclooxygenase-2 (COX-2) expression in normal human keratinocytes and squamous carcinoma cells. Based on these observations a prognostic role of COX-2 expression in laryngeal SCC can be hypothesized. Consequently, COX-2 expression was studied in laryngeal SCC (median follow-up = 47 months; range: 2-87 months) by quantitative immunohistochemistry (n = 61) and EGFR by binding assay (n = 51). Well-differentiated regions of laryngeal SCC revealed strong COX-2 immunostaining, whereas histologically normal areas neighboring tumor as well as poorly-differentiated tumors were negative. Immunohistochemical results were confirmed by Western blot analyses. Cox's regression analysis showed that the combination of low levels of COX-2 integrated density and high levels of EGFR covariates provided strong prediction, at 5-year follow-up, of both poor overall survival (chi(2) = 12.905; p = 0.0016) and relapse-free survival (chi(2) = 9.209; p = 0.01). In vitro studies on CO-K3 cell line, obtained from an EGFR positive, COX-2 negative poorly-differentiated laryngeal SCC, revealed that EGF stimulation failed to induce COX-2 expression and PGE2 production suggesting a change in EGFR signaling pathway. These findings indicate that COX-2 is overexpressed in less aggressive, low grade laryngeal SCC, whereas its expression is lost when tumors progress to a more malignant phenotype., (Copyright 2001 Wiley-Liss, Inc.)

Specimens of laryngeal squamous cell carcinoma (LSCC) were examined for epidermal growth factor receptor (EGFR) content using a radioreceptor method; 140 untreated consecutive patients with primary LSCC undergoing initial surgical resection were followed up for a median of 49 months (range 2-84 months) after surgery. Cox univariate regression analysis using EGFR as a continuous variable showed that EGFR levels were directly associated with the risk of lymph node metastasis. A significant relationship between EGFR status and cervical node metastasis was observed. The cutoff value of 20 fmol/mg protein was the best prognostic discriminator. The 5-year metastasis-free survival (MFS) was 66% for patients with EGFR- tumors compared with 15% for patients with EGFR+ tumors. By multivariate analysis, the EGFR status appeared to be a significant independent prognostic factor for MFS. Our results suggest that the assessment of EGFR status at the time of diagnosis may identify a subset of LSCC patients highly susceptible to neck node metastases thus defining therapy accordingly.

Quercetin and tamoxifen, in a range of concentrations between 0.01 and 5 microM, exert a dose-dependent inhibition on the anchorage-dependent and anchorage-independent cell growth of Hep2 and CO-K3 laryngeal cancer cell lines. Cell cycle analysis revealed that the growth-inhibitory effect was associated with a block of the cells at the G2/M checkpoint of the cell cycle followed by DNA fragmentation. This suggests that the failure of cells to proceed through the G2/M checkpoint can be a trigger for apoptosis. The induction of apoptosis by quercetin and tamoxifen was confirmed immunocytochemically by the in situ nick end labeling (TUNEL) reaction. These compounds also exerted a dose-dependent growth-inhibitory effect on primary tumor cells, as assessed by colony-forming assay and bromodeoxyuridine labeling. Laryngeal cancer cell lines and primary tumor cells expressed Type II estrogen binding sites (Type II EBS) with binding characteristics similar to those of Type II EBS in other tumor cells. Since the affinities of quercetin and tamoxifen for Type II EBS were correlated with their growth-inhibitory potential while ipriflavone neither interacted with these sites nor inhibited cell growth, the possibility exists that the action of these compounds is mediated, at least in part, by the interaction with Type II EBS. In conclusion, our data indicate that quercetin and tamoxifen could be potentially useful in laryngeal cancer treatment.

Sixty-three patients with primary laryngeal squamous-cell carcinoma were followed up for a median of 33 months after surgery. Cathepsin D (Cath D) concentration was assayed using a solid phase 2-site immunoradiometric assay in which the first monoclonal antibody (MAb) was coated on the ELISA solid phase and the second one, MIG8 radiolabeled with 1125-EGF, was used as the tracer. The median value of Cath D (13.8 pM/mg protein) was chosen as cut-off. Cath D > or = median value was closely related to neck lymph node involvement at presentation and to a short metastasis-free survival (MFS) and actual overall survival (OS). The 5-year MFS was 71% for patients with Cath D < median value tumors as compared with 0% for patients with Cath D > or = median value tumors. Lymph node status at presentation was not related to a short MFS and OS. Cox's univariate regression analysis using Cath D as a continuous variable showed that Cath D levels are correlated with neck lymph node metastasis. On multivariate analysis, Cath D status proved to be an independent factor for predicting a short MFS. Cath D assay may prove to be particularly useful in identifying laryngeal cancer patients who, with or without neck lymph node involvement at presentation, are at high risk of metastatic disease and poor outcome.

Epidermal-growth-factor-receptor(EGFR) expression was evaluated in 103 primary laryngeal tumors and in 42 normal laryngeal tissue specimens. Significantly higher EGFR levels were found in cancer specimens than in normal mucosa (p = 0.0053). EGFR expression did not correlate with age, tumor localization, T classification, cervical-lymph-node involvement or type of surgery, whereas it was higher in poorly differentiated tumors (G3) than in well/moderately differentiated (G1-G2) tumors (p < 0.05). Follow-up data were available for 74 patients. When EGFR status and the most important clinico-pathological characteristics were submitted to univariate analysis, tumor localization, type of surgery and EGFR status were found to be significantly correlated with disease-free survival. The 24-month disease-free survival rate was 58% for EGFR+ cancer patients and 82% for EGFR- ones. With multivariate analysis, only EGFR status and tumor localization were identified as significant independent prognostic parameters. Data reported here suggest that high EGFR levels may identify a sub-set of laryngeal-cancer patients with a particularly unfavorable prognosis.