Prognostic value of sentinel node biopsy in 327 prospective melanoma patients from a single institution.

AIM: To confirm the accuracy of sentinel node biopsy (SNB) procedure and its morbidity, and to investigate predictive factors for SN status and prognostic factors for disease-free survival (DFS) and disease-specific survival (DSS). MATERIALS AND METHODS: Between October 1997 and December 2004, 327 consecutive patients in one centre with clinically node-negative primary skin melanoma underwent an SNB by the triple technique, i.e. lymphoscintigraphy, blue-dye and gamma-probe. Multivariate logistic regression analyses as well as the Kaplan-Meier were performed. RESULTS: Twenty-three percent of the patients had at least one metastatic SN, which was significantly associated with Breslow thickness (p<0.001). The success rate of SNB was 99.1% and its morbidity was 7.6%. With a median follow-up of 33 months, the 5-year DFS/DSS were 43%/49% for patients with positive SN and 83.5%/87.4% for patients with negative SN, respectively. The false-negative rate of SNB was 8.6% and sensitivity 91.4%. On multivariate analysis, DFS was significantly worsened by Breslow thickness (RR=5.6, p<0.001), positive SN (RR=5.0, p<0.001) and male sex (RR=2.9, p=0.001). The presence of a metastatic SN (RR=8.4, p<0.001), male sex (RR=6.1, p<0.001), Breslow thickness (RR=3.2, p=0.013) and ulceration (RR=2.6, p=0.015) were significantly associated with a poorer DSS. CONCLUSION: SNB is a reliable procedure with high sensitivity (91.4%) and low morbidity. Breslow thickness was the only statistically significant parameter predictive of SN status. DFS was worsened in decreasing order by Breslow thickness, metastatic SN and male gender. Similarly DSS was significantly worsened by a metastatic SN, male gender, Breslow thickness and ulceration. These data reinforce the SN status as a powerful staging procedure.

[Lymphoepithelial cysts of the parotid gland: a pathology linked to HIV infection]. / Les kystes lymphoépithéliaux de la glande parotide: une pathologie liée à l'infection VIH.

We review the various lesions encountered in the parotid gland associated with HIV infection and propose guidelines for the management of a chronic parotid swelling in this setting. Lymphoepithelial cysts is the main diagnosis of parotid masses presented by HIV positive patients. This benign condition is diagnosed on cytology and the treatment is usually conservative. Patients with a diagnosis of lymphoepithelial cysts should be tested for HIV.

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.

[Treatment of laryngeal cancer: cordectomy or crico-hyoido-epiglottopexy versus radiotherapy]. / Traitement du cancer laryngé: cordectomie ou crico-hyoïdoépiglottopexie versus radiothérapie.

INTRODUCTION: Both radiotherapy and endoscopic or open functional surgery are recognised treatments for laryngeal cancer stage I and II. A comparison between two groups of patients treated with either modality may clarify the indications for both treatments. METHODS: Over a period of 13 years two separate series of patients were treated for laryngeal cancer (stage I and II) by either surgery (n = 72) or radiotherapy (n = 81). We have analysed and compared the two groups. RESULTS: Statistical analyses show a better local control among patients treated with surgery, when the anterior commissure was involved (p < 0.01) or with extension of the tumour (T2). However, long-term survivals were not significantly different in the two groups. As postradiation recurrence was diagnosed at an early stage, salvage (requiring total laryngectomy in many cases) was efficient but contributed to an appreciable difference in the long-term laryngeal preservation rate between the two groups (91% after radiotherapy and 99% after surgery). CONCLUSION: The treatment of laryngeal cancer must always compromise between oncological efficiency and functional preservation. With anterior commissure involvement (T1b) or more extensive disease (T2), surgery appears to be better. Therefore, preservation of perfect laryngeal function should be subordinate to oncological safety.

Supracricoid partial laryngectomy with cricohyoidoepiglottopexy and cricohyoidopexy for glottic and supraglottic carcinomas.

OBJECTIVES: To review the patients operated in our department with supracricoid partial laryngectomy with either cricohyoidoepiglottopexy (CHEP) (59 cases) or cricohyoidopexy (CHP) (10 cases) technique, for primary or recurrent glottosupraglottic squamous cell carcinoma and compare the technique with other surgical or conservative approaches for treatment of laryngeal carcinoma. METHODS: From hospital charts, we retrospectively reviewed 69 patients who had undergone supracricoid partial laryngectomy with the CHEP or CHP technique between 1983 and 1996 for primary or recurrent glottosupraglottic squamous cell carcinoma in our department. Statistical evaluation of oncological and functional results were conducted. Results were compared with other surgical and conservative treatment for glottosupraglottic carcinoma of the larynx that were published previously in the literature. RESULTS: Sixty-nine patients had CHEP or CHP for glottosupraglottic carcinoma of the larynx. Thirteen percent of the patients received adjuvant radiotherapy. Minimum follow-up was 2 years or until death. Five-year actuarial survival (Kaplan-Meier method) was 68%. Global local control was achieved in 84% of cases. Among previously untreated patients (n = 54), local control rate was 94.5%. After 1 year, 92.7% of patients achieved normal swallowing and respiration. Salvage total laryngectomy had to be performed in four patients (5.7%) for persistent aspiration and in five patients (7.2%), who were previously treated with radiotherapy, for local recurrence. No permanent tracheostomy or gastrostomy was required. CONCLUSIONS: Our experience with supracricoid partial laryngectomy with either CHP or CHEP suggests that this technique is a valuable alternative to radiotherapy for T2-T4 glottosupraglottic carcinomas, particularly those with extension and invasion of the anterior commissure. It allows for preservation of a good laryngeal function without altering the long-term survival, keeping total laryngectomy as a salvage procedure.

Evaluation of 250 free-flap reconstructions after resection of tumours of the head and neck.

BACKGROUND: Microvascular free-tissue transfer is now the primary method of reconstruction in many centres. The aim of this study was to evaluate the applications, complications and limitations of free-flap reconstruction in a series of patients with tumours of the head and neck. METHODS: This study reviewed prospectively accessioned computerized records in a dedicated head and neck database. Patients treated between 1987 and 1995 with a minimum of a 1-year follow-up were reviewed. There were 242 patients with a mean age of 58 years (172 men and 70 women). The most common tumour sites were oral cavity (42%), oropharynx (32%) and hypopharynx (11%). Mucosal squamous carcinoma accounted for 87% of primary cancers. RESULTS: Among the 250 free flaps, the radial forearm flap (205) and free jejunum (25) predominated. There were 21 episodes of vascular occlusion (8%), failure of 10 flaps (4%) and two patients died peri-operatively (0.8%). A second free flap was used in five of 10 cases of flap failure. The fistula rate was 4.4% among 203 patients at risk for this complication, which comprised four of 178 forearm flaps and five of 25 free jejunal grafts. Four of 16 jaw reconstructions failed. CONCLUSIONS: A 96% success rate was achieved using free-tissue transfer for head and neck reconstruction. The overall complication rate was low but jaw reconstruction and free jejunal grafts posed the greatest problems because of failure of radial bone and fistulas, respectively. The radial forearm septocutaneous flap was very reliable and remains our mainstay for oral reconstruction.

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.

Field cancerisation and polyclonal p53 mutation in the upper aero-digestive tract.

Field cancerisation of the aerodigestive tract is caused by chronic exposure to alcohol and tobacco, but the nature of the genetic alterations preceding overt malignancy is unknown. To identify potential field changes we have used a functional assay which tests the transcriptional competence of human p53 expressed in yeast. To increase the sensitivity and reliability of the technique for samples containing under 20% mutant p53, the 5' and 3'-ends of the p53 cDNA were examined separately. With this split form of the assay the tissue p53 mRNA acts as its own control for RNA quality. Mutations were detected in 87% (46/53) of tumours, reflecting the high sensitivity of the technique. Multiple biopsies of histologically normal tissue from the upper aero-digestive tract were tested and clonal p53 mutations were identified in 76% (38/50) of biopsies from patients presenting with multiple tumours compared with 32% (38/117) of biopsies from patients presenting with single tumours (P<0.000001). All patients (16/16) presenting with multiple tumours had at least one positive biopsy, compared with only 53% (19/36) of patients presenting with single tumours (P <0.001). This defines expansion of multiple clones of mutant p53-containing cells as an important biological mechanism of field cancerisation, and provides a means to identify patients likely to benefit from intensive screening for the development of new head and neck tumours.

A simple p53 functional assay for screening cell lines, blood, and tumors.

Mutations in the p53 gene are implicated in the pathogenesis of half of all human tumors. We have developed a simple functional assay for p53 mutation in which human p53 expressed in Saccharomyces cerevisiae activates transcription of the ADE2 gene. Consequently, yeast colonies containing wild-type p53 are white and colonies containing mutant p53 are red. Since this assay tests the critical biological function of p53, it can distinguish inactivating mutations from functionally silent mutations. By combining this approach with gap repair techniques in which unpurified p53 reverse transcription-PCR products are cloned by homologous recombination in vivo it is possible to screen large numbers of samples and multiple clones per sample for biologically important mutations. This means that mutations can be detected in tumor specimens contaminated with large amounts of normal tissue. In addition, the assay detects temperature-sensitive mutants, which give pink colonies. We show here that this form of p53 functional assay can be used rapidly to detect germline mutations in blood samples, somatic mutations in tumors, and mutations in cell lines.

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.