Free flap reconstruction in the treatment of tumors involving the hard palate.

AIM: To report our experience in free flap reconstruction of the hard palate after malignant tumor resection, in terms of reconstruction method, immediate post-operative course and subjective functional results. PATIENTS AND METHODS: Files from 1988 to 1999 were reviewed for patients having undergone microvascular reconstruction of the hard palate. The immediate post-operative course (during the first month) was reviewed to determine the occurrence of complications. The surgeon's evaluation 1 year post-operatively was used to determine the intelligibility of speech, type of diet and the quality of nasal permeability. RESULTS: Thirty eight patients (28 men and 10 women) with malignant tumors involving the hard palate had undergone surgical reconstruction using microvascular free flap techniques: free radial forearm flap (13 cases), scapular flap (24 cases) or fibular flap (five cases). Two different flaps were employed in two cases (scapula plus fibula). A second flap was used with success in two cases of failure of the first flap, for a total of 42 free flaps for 38 patients. Complications occurred in seven cases, with two cases of flap necrosis. At 1 year, 33 patients achieved a normal diet and 35 normal or easily intelligible speech. CONCLUSIONS: Microsurgical reconstruction using free tissue transfer allows reconstruction of large defects of the hard palate, with low morbidity and an excellent functional outcome. We propose criteria for free flap reconstruction and choice of flap.

Analysis of p53 serum antibodies in patients with head and neck squamous cell carcinoma.

BACKGROUND: Mutation of the p53 tumor suppressor gene (also known as TP53) often leads to the synthesis of p53 protein that has a longer than normal half-life. Mutant p53 protein that accumulates in tumor cell nuclei can be detected by means of immunohistochemical staining techniques. Serum antibodies directed against p53 protein (p53-Abs) have been detected in some cancer patients. PURPOSE: We assayed serum samples from 80 patients with head and neck squamous cell carcinoma (HNSCC) for the presence of p53-Abs, and we evaluated potential associations between the presence of these antibodies and other histopathologic and clinical features. METHODS: Serum was collected from each patient at the time of diagnosis. In addition, tumor biopsy specimens were obtained before the initiation of treatment. An enzyme-linked immunosorbent assay was used to detect p53-Abs. The accumulation of p53 protein in tumor cell nuclei was assessed immunohistochemically by use of the anti-p53 monoclonal antibody DO7. Patient treatment consisted of radiotherapy alone, primary chemotherapy followed by radiotherapy, or surgery and postoperative radiotherapy. Relapse-free and overall survival from the beginning of treatment were estimated by use of the Kaplan-Meier method; survival comparisons were made by use of the logrank statistic. Univariate and multivariate analyses were conducted to identify factors associated with survival. Reported P values are two-sided. RESULTS: Fifteen (18.8%) of the 80 patients had p53-Abs. Tumor cell nuclei in 43 (58.9%) of 73 assessable biopsy specimens exhibited strong p53 immunostaining. Patient treatment method and the accumulation of p53 protein in tumor cell nuclei were not associated with increased risks of relapse or death. In univariate analyses, advanced tumor stage (> T1 [TNM classification]) and the presence of p53-Abs were significantly associated with an increased risk of death (P for trend = .007 and P = .002, respectively), whereas advanced tumor stage, substantial regional lymph node involvement (> N1), and the presence of p53-Abs were associated with an increased risk of relapse (P for trend = .002, P = .02, and P < .0001, respectively). In multivariate analyses, advanced tumor stage and the presence of p53-Abs were significantly associated with increased risks of relapse (p for trend = .04 and P = .003, respectively) and death (P for trend = .04 and P = .03, respectively). At 2 years of follow-up, the overall survival proportion was 63% (95% confidence interval [CI] = 47%-80%) when no p53-Abs were detected compared with 29% (95% CI = 4%-54%) when p53-Abs were detected. Relapse-free survival at 2 years was 62% (95% CI = 49%-76%) if no p53-Abs were detected compared with 13% (95% CI = 0%-31%) if p53-Abs were detected. CONCLUSIONS AND IMPLICATIONS: The proportion of patients with HNSCC who have serum p53-Abs is smaller than that of patients exhibiting tumor cell accumulation of p53 protein. The presence of p53-Abs is significantly associated with increased risks of relapse and death.

Full-dose reirradiation for unresectable head and neck carcinoma: experience at the Gustave-Roussy Institute in a series of 169 patients.

PURPOSE: To review our experience using full-dose external reirradiation given with a curative intent for patients with unresectable head and neck carcinoma (HNC). PATIENTS AND METHODS: Between January 1980 and December 1996, 169 patients who presented with unresectable nonmetastatic HNC in a previously irradiated area were included in this series. The median time between the first and the second irradiation was 33 months. Reirradiation protocols were as follows: radiotherapy alone (65 Gy over 6.5 weeks at 2 Gy/d), 27 patients; Vokes protocol, ie, five to six cycles of radiotherapy (median total dose, 60 Gy; 2 Gy/d) with simultaneous fluorouracil (5-FU) and hydroxyurea, 106 patients; and bifractionated radiotherapy (median total dose, 60 Gy; 2 x 1.5 Gy/d) with concomitant mitomycin, 5-FU, and cisplatin, 36 patients. The median cumulative dose of the two irradiations was 120 Gy. Eighty-five percent of the tumors were squamous cell carcinoma, 14% undifferentiated carcinoma of nasopharyngeal type, and 1% adenocarcinoma. Forty-four percent were local recurrences, 23% nodal recurrences, 14% both local and nodal, and 19% second primary tumors. RESULTS: Mucositis grade 3 (World Health Organization [WHO]) was found in 32% and grade 4 in 14% of cases. Four patients presented with neutropenia or thrombocytopenia (grade 3 or 4 WHO). Late toxicities (> 6 months) were as follows: cervical fibrosis (grade 2 to 3 Radiation Therapy Oncology Group [RTOG]), 41%; mucosal necrosis, 21%; osteoradionecrosis, 8%; and trismus, 30%. Five patients died of carotid hemorrhage, apparently in complete remission. Six months after the onset of reirradiation, 37% of patients were in complete response. Patterns of failure were local only (53%), nodal only (20%), metastatic only (7%), and multiple (20%). Median follow-up time was 70 months. Overall survival rate (Kaplan-Meier) was 21% (95% confidence interval [CI], 15% to 29%) at 2 years and 9% (95% CI, 5% to 16%) at 5 years. Median survival time was 10 months for the entire population. Thirteen patients, of whom 12 were treated with the Vokes protocol, were long-term disease-free survivors. In a multivariate analysis, the volume of the second irradiation was the only factor significantly associated with the risk of death: relative risk=1.8 (95% CI, 1.13 to 5.7) (P=.01). CONCLUSION: Full-dose reirradiation combined with chemotherapy was feasible in patients with inoperable HNC. The incidence and severity of late toxicity was markedly increased in comparison to that observed after the first irradiation. Median survival was better than that generally obtained using palliative chemotherapy alone. A small proportion of patients were long-term disease-free survivors.

Cervico-facial adenoid cystic carcinoma: study of 102 cases. Influence of radiation therapy.

One hundred two patients with cervico-facial adenoid cystic carcinoma were treated with surgery alone, radiotherapy alone or both from 1951 to 1980. All the cases have a 5-year minimum follow-up. The local control rate is 55.5% at 5 years and 37.7% at 10 years. The 5-year local control rate is 44% with surgery alone, 65.8% with radiotherapy alone and 77.8% with post-operative radiotherapy. The difference between surgery alone and radiosurgical association is significant (p less than 0.01). The bone involvement diminished local control rate (32.2%/k 68.8%). The 5-year survival rate of the patients who recurred and have been retreated is 70.5%. The 5-year survival rate of the patients after the appearance of a metastasis is 38.1% and 2 patients have survived more than 10 years. The NED 5-year survival rate is 48.8%. There is no significant difference in the NED 5-year survival rate according to sites or treatments. The crude 5-year survival rate is 70%, 51.4% at 10 years and 32.2% at 15 years. Our study shows that adenoid cystic carcinoma have a peculiar and slow evolution. Surgery with post-operative radiotherapy obtains the best local control. These results and the radiosensibility of these lesions allow us to propose an aggressive treatment for the recurrence and the primary tumor of the directly metastatic patients.

Exclusive radiation therapy: the treatment of early tonsillar tumors.

One hundred and ninety-three T1 or T2 tumors of the tonsillar region have been treated by exclusive external irradiation between 1970 and 1982. Seventy-five percent of these tumors were classified as T2. There was no relationship between T and N stages. The nodal involvement was essentially linked to the macroscopic appearance of the tumor (superficial or nodular) and to the histology. The 5-year survival rate of the whole population was 58%. N stage and macroscopic appearance only influenced the survival. The local control was 88% for T1, 79% for T2. The main prognostic factors for local control were the histological type, with a 93% local control rate for poorly differentiated tumors versus 73% for well differentiated ones, and the macroscopic appearance, with a 83% local control rate for nodular tumors versus 75% for superficial ones. Superficial tumors spreading forward the anterior pilar have a higher local failure rate. All the patients' charts have been reviewed, and we observed a high percentage of marginal recurrences. The technique of irradiation, above all in case of a superficial tumor, must take into account the possibility of "geographic miss" and keep large safety margins.

Very accelerated radiation therapy: preliminary results in locally unresectable head and neck carcinomas.

PURPOSE: To report preliminary results of a very accelerated radiation therapy Phase I/II trial in locally advanced head and squamous cell carcinomas (HNSCC). METHODS AND MATERIALS: Between 01/92 and 06/93, 35 patients with an unresectable HNSCC were entered in this study. Thirty-two (91%) had Stage IV, and 3 had Stage III disease. The mean nodal diameter, in patients with clinically involved nodes (83%), was 6.3 cm. The median Karnovsky performance status was 70. The treatment consisted of a twice daily schedule (BID) giving 62 Gy in 20 days. RESULTS: In all cases, confluent mucositis was observed, which started about day 15 and resolved within 6 to 10 weeks. Eighty percent of patients had enteral nutritional support. The nasogastric tube or gastrostomy was maintained in these patients for a mean duration of 51.8 days. Eighteen patients (53%) were hospitalized during the course of treatment due to a poor medical status or because they lived far from the center (mean 25 days). Nineteen patients (56%) (some of whom were initially in-patients) were hospitalized posttreatment for toxicity (mean 13 days). Five patients (15%) were never hospitalized. During the follow-up period, 12 local and/or regional failures were observed. The actuarial 18-month loco-regional control rate was 59% (95% confidence interval, 45-73%). CONCLUSIONS: The dramatic shortening of radiation therapy compared to conventional schedules in our series of very advanced HNSCC resulted in: (a) severe acute mucosal toxicity, which was manageable but required intensive nutritional support in all cases; and (b) high loco-regional response rates, strongly suggesting that the time factor is likely to be critical for tumor control in this type of cancer.

Potential doubling time and clinical outcome in head and neck squamous cell carcinoma treated with 70 GY in 7 weeks.

PURPOSE: To study the predictive value of pretreatment potential doubling time and labeling index, as measured by flow cytometry in patients with head and neck squamous cell carcinoma treated with conventional radiotherapy. METHODS AND MATERIALS: 70 patients with a squamous cell carcinoma of the oropharynx and 4 patients with another involved head and neck site were entered in this prospective study. The duration of the S phase (TS), the labeling index (LI), and the potential doubling time (Tpot) were obtained by flow cytometry measurements of a tumor biopsy obtained after i.v. injection of 200 mg bromodeoxyuridine to the patient. The treatment consisted of 70 Gy in 7 weeks, 2 Gy per fraction and five fractions per week. RESULTS: The mean and median LI were 7.7% (standard deviation, SD: 5.0) and 6.3%, respectively. The mean and median TS were 9.3 h (SD: 3.6) and 8.3 h, respectively. The mean and median Tpot were 5.6 days (SD: 5.4) and 4.6 days, respectively. No significant relationship was found between the Tpot or LI and the tumor stage (T), nodal status (N), histological grade, and the site of the primary within the oropharynx. The only parameter significantly associated with an increased risk of local relapse was the tumor stage (p < 0.001). The mean Tpot for the group of tumors that relapsed locally was 5.3 days (SD: 3.3), compared to 6.1 days (SD: 4.08) for those who did not relapse locally (NS). Two parameters were significantly associated with a decrease in disease-free (DFS) and overall survival, namely the tumor stage (p < 0.005, and p < 0.001, respectively, for DFS and overall survival) and nodal involvement (p = 0.02 and (p < 0.005, respectively, for DFS and overall survival). The TS, LI, DNA index, and Tpot were not significantly associated with local relapse, DFS, and survival, either in the univariate or in the multivariate analysis. CONCLUSIONS: The method used to evaluate tumor cell kinetics did not provide clinically relevant kinetic parameters for this type of cancer. The classic prognostic factors (tumor stage and nodal status) were strongly associated with clinical outcome.

Squamous cell carcinoma of the upper aerodigestive tract associated with well-differentiated carcinoma of the thyroid gland.

The association of squamous cell carcinoma of the upper aerodigestive tract with well-differentiated thyroid carcinomas has rarely been reported in the literature. We report 10 cases illustrating this occurrence. In eight cases, the thyroid carcinoma was discovered accidentally on histological examination of a single neck node, a neck node dissection specimen, an unexpectedly found thyroid nodule, or a systematically resected thyroid lobe, all during surgical treatment of an upper aerodigestive tract carcinoma. In the other two cases, metastatic thyroid neck nodes appeared during the follow-up of a patient with an upper aerodigestive tract carcinoma. No case of upper aerodigestive tract carcinomas was found during the follow-up of thyroid cancer patients. In most cases, adequate thyroid cancer surgery was performed simultaneously or later. Prognosis was essentially determined by the upper aerodigestive tract cancer.

Olfactory esthesioneuroma: a report of 40 cases.

Olfactory esthesioneuroma is a rare malignant tumor arising in the olfactory epithelium. Forty cases observed at the Institut Gustave-Roussy from 1956 to 1987 are reported. This tumor usually grows slowly and is usually local, but it is important to be aware of the possibility of lymph node involvement (17%) and, particularly, of rapid development of distant metastases (25%), usually within 6 months. CT scan, and more recently, NMR have proved to be of value in choosing the surgical approach. In view of the usual point of departure, a combined neurosurgical and transfacial approach seems to be a satisfactory approach for obtaining oncological control of the lesion. The role of chemotherapy is discussed. The main prognostic factors seem to be the size of the lesion, the intracranial extension, and the lymph node involvement.

Salvage surgery by composite resection for epidermoid carcinoma of the tonsillar region.

Radiation therapy has usually been used as the primary treatment of squamous cell carcinoma of the posterior aspect of the oral cavity and the lateral aspect of the oropharyngeal walls. However, local failure occurs in a certain number of cases, depending on the initial tumor stage. One hundred thirty-four composite resections (transmaxillary buccopharyngectomies) have been performed as a salvage treatment at the Institut Gustave-Roussy, Villejuif, France, from January 1, 1976, through December 31, 1985, for local failure of epidermoid carcinomas treated initially by radiotherapy. Average time between primary irradiation and salvage surgery was 18 months. Most of the patients underwent some kind of supraomohyoid neck dissection. A myocutaneous flap was used in 18% of cases, which significantly reduced the rate of local complications. The nasogastric tube and the tracheostomy cannula were removed after a median delay of 23 days and 24 days, respectively. Early postoperative local complications occurred in 45% of cases; most of them were minor. A new locoregional recurrence occurred in approximately half of the patients and was usually fatal. Overall survival after salvage surgery was 34% at 3 years and 23% at 5 years. The only statistically significant prognostic factor was the adequacy of surgical margins.

Basaloid squamous carcinoma of the head and neck. Immunohistochemical comparison with adenoid cystic carcinoma and squamous cell carcinoma.

Basaloid squamous carcinoma (BSC) is a rare distinct variant of squamous cell carcinoma of the head and neck region. This entity may commonly pose diagnostic difficulties, especially on small biopsy material. We report the clinicopathological characteristics of 12 new cases and compare their immunohistochemical features with those of solid adenoid cystic carcinomas and conventional squamous cell carcinomas. Our results show that neoplastic BSCs and squamous cell carcinomas do not react to vimentin and S100 protein, while adenoid cystic carcinomas manifest both. The BSCs, however, are S100 protein-positive in intratumoral dendritic Langerhans' cells that are lacking in squamous cell and adenoid cystic carcinomas. Our findings indicate that the immunohistochemical differences between BSC and adenoid cystic carcinoma could assist in their differential diagnosis.

Undifferentiated carcinoma of nasopharyngeal type of tonsil.

A review of 2262 squamous cell carcinomas of the tonsillar region seen at the Institut Gustave-Roussy, Villejuif, France, from 1970 to 1986 showed 1837 well- and poorly differentiated squamous cell carcinomas and 425 undifferentiated squamous cell carcinomas. Eighteen patients with undifferentiated squamous cell carcinomas presented histologic characteristics of undifferentiated carcinomas of nasopharyngeal type. Radiosensibility and radiocurability (complete sterilization with 70 Gy administered) was found in this group with an excellent long-term control of local disease (77% at 10 years actuarial). Epstein-Barr virus-related serologic tests were performed for seven patients. Four of them presented the serologic anti-Epstein-Barr virus titer patterns, generally associated with undifferentiated carcinomas of nasopharyngeal type (1280 to 5120 for viral capsid antigen/IgG and 40 to 320 for viral capsid antigen/IgA). These observations confirm that undifferentiated carcinomas of the nasopharyngeal type may arise outside the nasopharynx.

Reconstruction with free jejunal autograft after circumferential pharyngolaryngectomy: eighty-three cases.

The free jejunal autograft (FJA) has become a common procedure for pharyngeal reconstruction after circumferential pharyngolaryngectomy. In order to evaluate the postoperative outcome and the functional and carcinologic results, we retrospectively reviewed 83 cases of reconstruction with FJA. Fifty-one patients had received no prior radiotherapy, and 25 had received prior radiotherapy for their hypopharyngeal tumor or for another previous primary. Seven patients underwent a secondary reconstruction. In the postoperative course, there were 2 postoperative deaths, 4 graft failures (5%), and 11 salivary fistulas. The median time to removal of the nasogastric tube was 16 days, and to discharge, 23 days. Forty-eight patients received postoperative radiotherapy, with good tolerance. At 1 year postoperatively, 98% of the patients were able to eat a solid or soft diet. The postoperative radiotherapy did not impair the quality of the functional results in a long-term assessment. The vocal results were disappointing. The 3-year survival rate was 40%. The main carcinologic failures (45 patients) were locoregional recurrences (20 patients) and metastasis, which was the cause of death in 34% of the cases. It seems clear that FJA allows one-stage reconstruction and good swallowing rehabilitation, tolerates postoperative radiotherapy, and increases the quality of life in these patients with a poor prognosis.

[Nasal-sinusal inverted papillomas]. / Papillomes inversés naso-sinusiens.

The authors report on 19 cases of Inverted Papilloma collected over ten years at the Institut Gustave-Roussy. The Inverted Papillomas are rare tumors affecting predominantly adult males. This slow progressing tumor is usually revealed by unilateral nasal obstruction (68%). Its loco-regional extension is best appreciated by radiologic and tomodensitometric scanning. After limited surgical resection, the tumor may either recur (11 out of 19 cases) or show malignant evolution (9 out of 19 cases). Histopathologic criterias of this latter possibility are discussed. A radical surgical treatment such as paralateronasal rhinotomy may prevent the malignant transformation of this benign tumor.

Clear cell carcinoma arising in pleomorphic adenoma of the minor salivary gland.

Malignant change arising in pleomorphic adenoma of the salivary glands is uncommon, with a reported incidence of 2-10 per cent. Only one case where a pleomorphic adenoma became a clear cell carcinoma appears to have been published in the English literature. An additional case of clear cell carcinoma arising in pleomorphic adenoma of a minor salivary gland is reported and the relevant literature discussed.

Combined transfacial and neurosurgical approach to malignant tumours of the ethmoid sinus.

In order to understand the risks and benefits of a combined transfacial and neurosurgical procedure for neoplasms of the ethmoid sinus, we reviewed all patients who underwent this surgical approach in our department between 1986 and 1994. The study included 41 patients. Pathological diagnoses included adenocarcinoma (31 patients), squamous cell carcinoma (three patients), aesthesioneuroblastoma (three patients), other (four patients). The overall morbidity rate was 39 per cent, and the post-operative mortality rate was 2.5 per cent. Complications were statistically more likely in patients with bone skull base reconstruction. The main carcinologic failures were local recurrences (24 per cent) and metastases (22 per cent). The one-year, three-year and five-year Kaplan Meir survival rates were respectively 84 per cent, 53 per cent and 36 per cent. In conclusion, the mortality and morbidity were acceptable, especially when no bone skull base reconstruction was performed. Better local control justifies a combined procedure with post-operative radiotherapy when tumours involve or reach the skull base.

Aesthesioneuroblastoma.

Forty patients were treated or followed up for aesthesioneuroblastoma between 1980 and 1995 at Institut Gustave Roussy, France. There were three T1, seven T2, 15 T3 and 15 T4 lesions. The cervical metastatic rate at presentation was 18 per cent. Distant metastases were detected by bone marrow biopsy and bone scan in three patients at presentation. Treatment modalities included surgery alone in eight patients, radiotherapy alone in three patients, combined modality surgery plus radiotherapy in 11 patients, chemotherapy alone in two patients, chemotherapy plus radiotherapy in 10 patients, and multimodality therapy chemotherapy plus surgery plus radiotherapy in six patients. The five-year survival rate was 51 per cent. Multimodality treatment offered better survival (63 per cent at five years) and disease-free interval (54 months). Overall local, regional, and distant failure rates were 58 per cent, 15 per cent and 40 per cent respectively. Distant metastases commonly occurred in bone (82 per cent). Cervical metastasis was an unfavourable prognostic indicator (0 per cent survival at two years). In conclusion, aesthesioneuroblastoma is sensitive to chemotherapy and radiotherapy. Multimodality therapy should be used initially.

[Myoepithelioma (or myoepithelial cell adenoma). Report of a case]. / Myo-épithéliome (ou adénome à cellules myo-épithéliales). A propos d'un cas.

One case of myo-epithelioma occurring in the parotid gland is reported. This tumor was composed of spindle cells. The diagnosis was confirmed by ultrastructural and immunohistochemical analysis demonstrating myofilaments aggregation pattern and positive staining for S100-protein and keratin antibodies. Of all salivary gland tumors, myo-epithelioma accounts for less than 1% of the total and has a good prognosis. Conservative surgical management is curative.

[Métastases of carcinoma of the kidney to the salivary glands. A case of intraparotid metastasis (author's transl)]. / Les métastases des cancers du rein au niveau des glandes salivaires. A propos d'un cas de métastase intraparotidienne.

The authors first report the histopathological distribution of 111 parotidectomies carried out between 1965 and 1975. They then describe a case of a malignant tumour of the parotid which was shown by histological examination to be a metastasis of a carcinoma of the kidney, this being the first manifestation of the primary tumour. Finally, the authors review the literature concerning metastases of carcinoma of the kidney to the ENT area. They feel that the great rarity of parotid localisations is due to the fact that they may be confused with an acinous carcinoma of the parotid if histochemical stains are not used.

[Severe emergency epistaxis]. / Les épistaxis graves en service d'urgence

Selective ligature of the nutrient vessels of the nasal mucosa is an effective method of controlling massive epistaxis. Careful identification of the site of the haemorrhage is essential. One cause of immediate failure was an error in indication and another, lack of precision in locating a vascular tumour. With a short stay in hospital (the average is a week) we have achieved complete control over almost every very serious case of epistaxis we have been called upon to treat. Surgical sequelae have been minimal. In particular we found no mucosal vasomotor disorders such as those described in some operations involving the back of the pterygo-maxillary fossa.