Activation of the extracellular signal regulated kinase (ERK) pathway in human melanoma.

BACKGROUND: Several studies suggest that melanoma may be resistant to treatment because of resistance to apoptosis and that this may be the result of activation of the extracellular signal regulated kinase (ERK1/2) pathway. AIMS: To test this hypothesis by examining the expression of ERK1/2 and its activated form in histological sections of melanoma and its relation to known prognostic features of the disease. MATERIALS/METHODS: Immunohistochemistry with antibodies to ERK1/2 and phosphorylated ERK (p-ERK) was performed on formalin fixed sections from 42 primary melanomas, 38 metastases, and 20 naevi. Fourteen of the primary melanomas were in the radial and 28 in the vertical growth phase. RESULTS: ERK1/2 was widely expressed (100%) in all the (pigmented) lesions studied. p-ERK1/2 expression was much lower in compound (32.4%) and dysplastic (54.5%) naevi than in primary melanoma (nodular 78.8%, superficial spreading 67%) and subcutaneous metastases (76.3%). p-ERK expression was much lower in lymph node metastases (48.5%), suggesting that the microenvironment may influence the activation of ERK. There was a (non-significant) trend for p-ERK expression to be higher in thick (>1.0 mm) versus thin (< or =1.0 mm) melanoma (p = 0.23). There was a trend for overall survival to be related to p-ERK expression in patients with melanoma over 1 mm in thickness. CONCLUSIONS: Expression of activated ERK1/2 in melanocytic lesions appears to be related to malignant potential so that activation of ERK1/2 may be important in melanoma progression. These results provide important histological support for the proposal that inhibition of this signalling pathway may be useful in treatment of melanoma.

Horizontal partial laryngectomy for supraglottic squamous cell carcinoma.

Between 1981-1999, 75 patients treated for supraglottic SCC with horizontal supraglottic laryngectomy (HSL) at the Otolaryngology Head and Neck Surgery Department of Lausanne University Hospital were retrospectively studied. There were 16 patients with T1, 46 with T2 and 13 with T3 tumors. Among these, 16 patients (21%) had clinical neck disease corresponding to stage I, II, III and IV in 12, 39, 18 and 6 patients, respectively. All patients had HSL. Most patients had either elective or therapeutic bilateral level II-IV selective neck dissection. Six patients (8%) with advanced neck disease had ipsilateral radical and controlateral elective II-IV selective neck dissections. Adjuvant radiotherapy was given to 25 patients (30%) for either positive surgical margins (n=8), pathological nodal status (n=14) or both (n=3). Median follow-up was 48 months (range, 24-199). Five-year disease-specific survival and locoregional and local control were 92, 90 and 92.5%, respectively. Among five patients who were diagnosed with local recurrence, one had a total laryngectomy (1.4%); the others were treated by endoscopic laser surgery. Two patients had both a local and regional recurrence. They were salvaged with combined surgery and radiotherapy, but eventually died of their disease. Cartilage infiltration seems to influence both local control (P=0.03) and disease-specific survival (P=0.06). There was a trend for worse survival with pathological node involvement (P=0.15) and extralaryngeal extension of the cancer (P=0.1). All patients except one recovered a close to normal function after the treatment. Aspiration was present in 16 patients (26%) in the early postoperative period. A median of 16 days (7-9) was necessary to recover a close to normal diet. Decannulation took a median of 17 days (8-93). Seven patients kept a tracheotomy tube for up to 3 months because of persistent aspiration. There was no permanent tracheostomy or total laryngectomy for functional purposes. Horizontal supraglottic laryngectomy remains an adequate therapeutic alternative for supraglottic squamous cell carcinoma, offering an excellent oncological outcome. The postoperative functional morbidity is substantial, indicating the need for careful patient selection, but good laryngeal function recovery is the rule. The surgical alternative is endoscopic laser surgery, which may offer comparable oncological results with less functional morbidity. Nevertheless, these two different techniques need to be compared prospectively.

Total thyroidectomy for clinically benign disease of the thyroid gland.

BACKGROUND: The role of total thyroidectomy in the treatment of patients with benign thyroid disease remains controversial. However, this procedure may be appropriate when both thyroid lobes are involved and when the risk of recurrence is significant. This study is a review of a 15-year experience of total thyroidectomy for benign disease. METHODS: Between 1988 and 2002, 834 patients underwent total thyroidectomy for clinically benign disease at the Sydney Head and Neck Cancer Institute, Royal Prince Alfred Hospital. There were 128 men and 706 women with a mean age of 52 (range 16-91) years. Indications for surgery were euthyroid multinodular goitre (MNG), toxic MNG and Graves' disease in 730 (87.5 per cent), 57 (6.8 per cent) and 47 (5.6 per cent) respectively. A total of 74 patients had previously undergone partial thyroidectomy. RESULTS: The incidence of temporary recurrent laryngeal nerve palsy was 2.3 per cent and that of temporary hypoparathyroidism 14.4 per cent. Permanent recurrent laryngeal nerve palsy occurred in 1.1 per cent, and 2.4 per cent of patients had permanent hypoparathyroidism. Neither the initial clinical diagnosis nor a history of previous treatment significantly influenced the rate of complications. The incidence of malignancy, other than incidental microscopic papillary carcinoma, was 4.6 per cent. CONCLUSION: Total thyroidectomy has an important role in the management of patients with benign disease when both lobes of the thyroid gland are involved. This approach avoids disease recurrence and the increased risk of morbidity associated with secondary operation.

Treatment of early stage squamous-cell carcinoma of the glottic larynx: endoscopic surgery or cricohyoidoepiglottopexy versus radiotherapy.

BACKGROUND: Both surgery and radiotherapy are recognized treatments of T1-T2 squamous cell carcinoma of the larynx. We retrospectively analyze and compare the oncological outcome of patients treated in a single institution, either by endoscopic surgery or partial supracricoid laryngectomy versus radiation therapy. METHODS: The medical records of 156 patients treated between 1983 and 1996 with either surgery (n = 75) or radiotherapy (n = 81) were reviewed. Male to female ratio, median age, and T-stage distribution were comparable. RESULTS: With a median follow-up time of 59 months, the 5-year cause-specific survival rate of 93% was identical for both groups. The actuarial incidence of metachronous second primaries was 7% at 5 years. Local control at 5 years remained 84% after surgery and 77% after radiotherapy. Anterior commissure infiltration was shown to represent a negative predictive factor of local control for radiotherapy (p =.01). Salvage treatment brought ultimate local control to 96% of patients after surgery and 94% after radiation therapy with long-term laryngeal preservation rate altered significantly (p =.05) in the group of patients who received radiotherapy (90.1% vs 97.4%). CONCLUSION: The treatment of laryngeal cancer is always a compromise between oncological efficiency and preservation of function. Our data suggest that, assuming proper selection of patients, radiation therapy and surgery yield similar local control and survival rates. The functional disadvantages after surgery are moderate and clearly counterbalanced by a significant decrease in long-term laryngeal preservation rate after radiotherapeutic treatment.

Facial nerve function after parotidectomy.

OBJECTIVES: To analyze the incidence of facial nerve dysfunction following parotidectomy and to correlate this with the extent of parotid gland resection, the pathological diagnosis, and the clinical setting. DESIGN: A review of prospectively collected data from a dedicated computerized head and neck database. SETTING: Tertiary care center. PATIENTS: Between 1987 and 1995, 248 patients underwent 259 parotidectomies performed by the same surgeon (C.J.O'B.). Indications were clinical tumor (n=213) or sialadenitis (n=46). There were 235 previously untreated patients and 13 who had undergone a prior operation on that side. Facial nerve function was normal in 242 patients and abnormal before surgery in 6. Cancers accounted for 88 parotidectomies and benign disease accounted for 171. Of 213 clinical tumors, 41 (19%) were situated deep to the plane of the facial nerve. RESULTS: The facial nerve was intentionally sacrificed in 28 of 259 operations (18 total and 10 partial sacrifice). In 230 parotidectomies in which facial nerve function was normal before surgery and the nerve was preserved, the incidence of initial postoperative facial weakness was 29%. Based on the diagnosis and extent of surgery, rates of facial weakness were 16.5% and 13%, respectively, for benign and malignant tumors located in the superficial lobe and treated with limited superficial parotidectomy; 30% and 34% for sialadenitis treated with complete superficial parotidectomy and near-total parotidectomy, respectively; 31% and 100%, respectively, for benign and malignant lobe tumors treated with near-total parotidectomy; 83% for parotidectomy associated with a neck dissection; and 33% for patients who had previous parotid surgery. Permanent weakness occurred in 13 (5.6%) of 230 patients, but 10 of these 13 had simultaneous neck dissection and facial nerve dysfunction involved only the marginal mandibular branch. Recovery of normal facial movements occurred within 6 months in 46 (68%) of 67 of those with initial weakness. CONCLUSIONS: The likelihood of temporary facial weakness correlated with the extent of surgery and was especially influenced by tumor location deep to the plane of the facial nerve, previous parotid surgery, a diagnosis of sialadenitis, and the addition of neck dissection to the parotidectomy. Permanent weakness mainly affected the marginal mandibular branch when neck dissection was included.

Pneumoblastoma in neurofibromatosis.

Pneumoblastoma is a rare tumor composed of two histologic cell types, arising from epithelium and stroma. Patients with von Recklinghausen's disease are known to develop certain types of tumors. A rare, and possibly first case of pneumoblastoma arising in a patient with neurofibromatosis is described.