Purpose: Surgical margin status is reported to be a relevant prognostic factor in head and neck squamous cell carcinoma (HNSCC), associated
with a high risk of local recurrence. This study examines ...whether gene-promoter hypermethylation could be detected in HNSCC
surgical margins with no histologic evidence of malignancy, and if so, whether it reflects epigenetic events of primary tumors.
Experimental Design: Promoter methylation status of MGMT, p16 , and DAP-K genes was evaluated by methylation-specific PCR in 20 primary HNSCC tumors. Histopathologically negative surgical margins
of hypermethylated tumors were collected, and their methylation status compared with the primary tumor status.
Results: Promoter hypermethylation in at least one of the three tested genes was detected in 65% (13 of 20) of tumors. MGMT was hypermethylated in 50% (10 of 20), DAP-K in 45% (9 of 20), and p16 in 20% (4 of 20) of tumors. Methylation status was analyzed in 35 margins from 11 of 13 patients showing promoter hypermethylation
in the tumor tissue. Identical methylation events were seen for at least one gene in primary tumor and surgical margins in
9 of 11 cases (82%). Association was found for gene-specific hypermethylation status in tumors and paired surgical margins,
and gene-specific concordance was 63% for MGMT ( κ = 0.24), 90% for DAP-K ( κ = 0.74), and 90% for p16 ( κ = 0.79).
Conclusions: Our results support the hypothesis that detection of gene promoter hypermethylation in HNSCC tumor cells–free surgical margins
may be a helpful biomarker to identify molecularly altered fields in areas adjacent to the tumor.
Angiogenesis is essential for the development and progression of malignant tumours, and there is increasing evidence that microvessel density (MVD) can be considered an indirect marker of ...neo-angiogenesis. However, there is still disagreement concerning the clinical relevance and prognostic significance of MVD in head and neck squamous cell carcinomas (HNSCCs). MVD was evaluated in 127 HNSCC patients by means of immunohistochemistry using monoclonal antibodies (mAbs) against CD34 and CD105 (endoglin), which has recently been described as a potent marker of neo-vascularisation in various malignancies. MVD was expressed as the mean number of vessels/mm
2. The mean CD34+ and CD105+ MVD values were significantly higher in T3–T4 tumours and those in an advanced clinical stage; furthermore, CD105+ MVD was significantly higher in N+ tumours. The patients with a high CD105+ MVD had a significantly shorter disease-free and overall survival; CD34+ MVD was not associated with survival. Similarly, in the subset of lymph-node negative patients, higher CD105+ MVD values were significantly associated with either OS and DFS. Multivariate analysis showed that a high CD105+ MVD was the only independent marker of tumour recurrence or death. Our data suggest that CD105+ MVD may represent an additional prognostic factor in HNSCC patients providing more accurate data for the determination of prognosis and management in the subset of lymph node negative patients.
To examine the utility of swallowing therapy (ST) before and after surgery in patients undergoing subtotal laryngectomy.
From 1990 to 2000, 43 patients underwent subtotal laryngectomy. Prior to 1997 ...patients received ST only after surgery, while from 1997 on, patients scheduled for subtotal laryngectomy also received some sessions of ST before surgery.
The average time to swallowing resumption was 27.76 +/- 5.206 days for the 25 patients who received ST only after surgery, and 16.38 +/- 2.953 for those who underwent ST both before and after surgery.
The difference between the two groups was significant on Student's t test (P < 0.001) and shows that preoperative rehabilitation is of significant help in the early resumption of normal deglutition.
The authors find that the duration of nasogastric tube feeding is reduced in subjects who underwent ST.
Vinorelbine and docetaxel are two effective drugs in esophageal cancer; our purpose was to evaluate efficacy and toxicity of a combination of these drugs in recurrent squamous cell esophageal cancer. ...Twenty patients previously treated with concomitant chemoradiotherapy (n = 14), surgery alone (n = 2), surgery plus radiotherapy (n = 2), or concomitant chemoradiotherapy + surgey (n = 2) were enrolled. Thirteen patients had a local-regional recurrence, two patients had metastases, and five patients had both. The doses were 80 mg/m(2) for docetaxel and 20 mg/m(2) for vinorelbine on d 1 every 21 d for a maximum of six cycles. Twenty patients received a total of 106 cycles (median per patient, 5). Neutropenia was the most frequent and severe side effect (grade 4 in 80%; grade 3 in 20%). The overall response rate was 60%, which included 3 of 20 complete responses (15%) and 9 of 20 partial responses (45%). Median response duration was 7 mo (2-50+). Overall median survival was 10.5 mo (range, 2-55+). A dysphagia improvement was observed in 81% of patients. In conclusion, the data from this phase II study indicate that this combination is effective in recurrent heavily pretreated patients with a short-lasting manageable toxicity.
Twenty patients with recurrent, inoperable head and neck squamous cell carcinoma received perilymphatic injections of natural interleukin-2 (nIL-2) for 10 days. Ten patients received 200 units (U) of ...nIL-2; five 1,000 U; and five 5,000 U. Irrespective of the location of the recurrence, the injections were always performed 1.5 cm below the insertion of the sternocleidomastoid muscle on the mastoid. When the ipsilateral lymphatic chain was still present, they were performed on the same side as the tumor site, whereas when it had been stripped as a result of previous surgery, they were contralateral. Patients who had undergone bilateral neck dissection were injected on the tumor side. Whenever possible, the treatment was repeated after 45-day intervals. In 13 patients (65%) with bilateral or contralateral lymph nodes, complete or partial disappearance of the lesion was observed. Despite these marked responses, the tumor always relapsed, and subsequent IL-2 courses were poorly effective. There were no systemic disturbances during or after treatment, but only moderate local swelling and pain.
