Paraneoplastic dermatomyositis accompanying nasopharyngeal carcinoma: diagnosis, treatment and prognosis.

Dermatomyositis (DM) is a multisystem inflammatory disorder primarily affecting the skin and muscles. Its pathophysiology is still very poorly understood, but humoral and cellular immune dysregulation is apparent. Diagnosis of DM is based on five criteria: proximal limb muscle weakness, serum muscle enzyme elevation, histopathologic muscle abnormalities on muscle biopsy, electromyographic abnormalities, and clinical inflammatory dermatological manifestations (heliotrope rash, poikiloderma, and inflammatory lesions on the hands and facing joints). DM is frequently associated with certain cancers, and may appear before, concurrent with, or after diagnosis of cancer. DM has been reported to be associated with approximately one per 1000 cases of nasopharyngeal carcinoma. Treatment is based on long-course nonselective immunosuppression, particularly corticosteroids, by general route, even when malignancy is present, but new-targeted therapies may modify the treatment strategy in the near future. Despite iatrogenic immunosuppression, the prognosis of nasopharyngeal cancer is not worse in patients with paraneoplastic DM. We report one case as an illustration of this paraneoplastic course (evolving in parallel with the cancer), and to make an update on the state of knowledge on paraneoplastic DM in such cancers.

Botulinum toxin A for quality of life improvement in post-parotidectomy gustatory sweating (Frey's syndrome).

OBJECTIVE: To measure patient-reported quality of life before and after botulinum toxin A treatment of post-parotidectomy Frey's syndrome (gustatory sweating). PATIENTS AND METHODS: A questionnaire concerning functional, social and emotional aspects of Frey's syndrome (14 questions, with responses on a zero to three point scale) was administered to 17 patients (13 women and four men) before and one month after intradermal injection of botulinum toxin A. Parotidectomy had been performed one to 19 years previously, for benign (n = 10) or malignant (n = 7) tumours, with gustatory sweating occurring a median of 15 months after surgery (range: one month to 14 years). Pre- and post-treatment quality of life scores were compared using Wilcoxon's test (p < 0.05). RESULTS: Patients' reported functional quality of life improved significantly (p = 0.0004). Their social and emotional scores were not significantly modified (p = 0.155 and 0.142, respectively). Seven patients (41 per cent) found the injections painful, but all patients said that the effects were beneficial, that they would undergo new injections if necessary and that they would recommend this treatment to other patients. The benefit lasted over 1.5 years for 60 per cent of patients. No correlation was found between duration of the effect and the extent of parotidectomy (p = 0.067). CONCLUSIONS: Botulinum toxin A significantly improved patients' functional quality of life, without significant improvement in their social or emotional quality of life, according to our questionnaire results. The duration of the effect was longer than the reported physiological effect of botulinum toxin A on acetylcholine receptors.

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.

[Laryngeal Preservation with Induction Chemotherapy. Experience of two GETTEC Centers, Between 1985 and 1995]. / Préservation laryngée par chimiothérapie d'induction.

This is a retrospective study of laryngeal preservation in endolaryngeal cancer with induction chemotherapy and radiotherapy for good responders. Between 1985 and 1995, 104 patients were treated in Institut Gustave Roussy (87 patients) and in Limoges (17 patients). The overall survival for the whole population was 76% and 69% at 3 and 5 years respectively, with a 36% rate of laryngeal preservation. In this retrospective series of patients, the single prognostic factor affecting survival was arytenoid mobility before treatment (66% and 55% at 3 years vs 85% and 82% at 5 years; p<0.004). Loco-regional failures were higher (33% vs 15%, p<0.03), and laryngeal preservation was lower (18% vs 51%) among patients with a fixed arytenoid (49 pts), compared with patients with a non fixed arytenoid (55 pts) ). The percentages of patients with a fixed arytenoid could explain the conflicting results of the two randomized studies of laryngeal preservation in laryngeal cancer.

Subtotal laryngectomy with cricohyoidopexy as first treatment procedure for supraglottic carcinoma: Institut Gustave-Roussy experience (146 cases, 1974-1997).

PATIENTS AND METHODS: Between 1974 and 1997, 297 patients underwent a subtotal laryngectomy at the Institut Gustave-Roussy; 146 of these patients underwent cricohyoidopexy (CHP) for a supraglottic primary as their first treatment. The majority of patients were men (137) aged from 33 to 78 years (median 54 years). The tumour stage at presentation was T1 in 2, T2 in 87, T3 in 53 (preepiglottic space involvement), and T4 (minimal thyroid cartilage invasion) in 4 patients. One hundred and twenty-five patients were N0 (86%) and 21 patients were Np (palpable); 98% had homolateral and 55% had bilateral neck dissections. RESULTS: One patient died postoperatively of a myocardial infarction and 68% patients had an uneventful course. Aspiration was the commonest complication (23 patients, 19%). The median time to removal of the tracheotomy cannula was 10 days and for the nasogastric tube 21 days during the past 10 years. Completion of subtotal laryngectomy into total laryngectomy was done in 21 cases (15%): eight times because of oncological events [five local failures, two second primary (hypopharynx), one positive margin] and 13 times because of aspiration (9%). There were six local failures (4%) and eight nodal failures (5%). The rates of distant metastases and second primaries were 6% and 16% respectively. Half of the local and nodal failures were subsequently sterilized. Findings at death were two local recurrences, four nodal recurrences, eight distant metastases, and 11 second primaries. The 3- and 5-year overall survival rates were 92% and 88% respectively, with an overall laryngeal preservation rate of 86%. CONCLUSION: When supraglottic laryngectomy is not feasible for supraglottic cancer, subtotal laryngectomy with CHP is a safe and effective oncological procedure, with preservation of satisfactory laryngeal function.

Surgical management of posterior pharyngeal wall carcinomas: functional and oncologic results.

BACKGROUND: The optimal primary treatment for posterior pharyngeal wall tumors remains controversial. METHODS: To assess the relevance of surgical treatment from a functional and oncologic point of view, we reviewed the cases of 77 patients surgically treated between 1984 and 1995. Among them 23 had been previously irradiated. Fifty-five patients underwent a conservative surgery (CS) sparing the larynx; 19 direct closures, 6 reconstructions of the posterior wall with a thoracic myocutaneous flap, 15 with a platysma flap, and 15 with a free forearm flap were performed. Twenty-two patients underwent radical surgery (RS). All previously untreated patients had postoperative radiotherapy. The functional assessment concerned the CS group. Oncologic results, especially local control and survival were studied for the whole group. RESULTS: Of the 55 patients who underwent CS, 53 (96%) had their canula and 49 (89%) their feeding tube removed. At 1 year, in the platysma and free forearm groups, 21 of the 24 assessable patients were back to exclusive oral intake. For patients treated by primary surgery followed by radiotherapy, the rate of local failure was 11% (18% for tumors greater than 4 cm), and the 5-year survival rate was 35%. For patients who had previous radiotherapy, the rates were, respectively, 52% and 16%. CONCLUSION: The satisfactory functional results, caused by the improvement of reconstructive procedures, allow conservative surgery even in the case of large tumors. Oncologic results, especially local control, suggest that primary surgery followed by radiotherapy is effective for the treatment of posterior wall cancer. The oncologic results of surgery in a previously irradiated area are poor, and CS is not recommended in these cases.

[Mandibulotomy for cancer of the oral cavity and oropharynx: functional and carcinologic outcome in 107 cases]. / La chirurgie par voie de mandibulotomie dans les cancers de la cavité buccale et de l'oropharynx. Résultats fonctionnels et carcinologiques sur une série de 107 cas.

We report a series of 107 patients who underwent mandibulotomy at the Gustave-Roussy Institute, France for cancer of the oral cavity and orophaynx between 1998 and 1996. The most common tumor site was the base of the tongue. Most cases were stage T2 or T3. Postoperative radiotherapy was employed except in those who had previous irradiation, either for the same tumor (12 cases) or another cancer (16 cases). The different types of mandibulotomies and osteosynthesis methods were analyzed in relation to postoperative course and functional and oncological outcome at mean follow-up of 6 years. Osteitis was the most frequent complication (14%) requiring hemimandibulectomy in 5 cases. Complications occurred particularly when osteosynthesis was in the pre-or postoperative irradiation field. Osteosynthesis was definitive in 79.4% with good functional results in 76.5%. Previous radiotherapy or use of flaps for closure gave poor function results. We emphasize the advantages of anterolateral mandibulotomy and titanium plates. The local control rate was 81.5% at 6 months and overall survival rat was 51.5% at 5 years with no significant impact of tumor site on survival.

[Cancers of the cavum]. / Cancers du cavum.

Nasopharyngeal carcinoma (NPC) is a clinical entity different from other epidermoid carcinomas of the head and neck. It is distinguished by its particular histology, its geographic distribution, its special serologic and biologic relationship to Epstein-Barr Virus (EBV); its natural history NPC occurs more frequently in young men (25-40 years). NPC is one of the most aggressive tumors of the head and neck with a very high rate of cervical nodes and systemic dissemination. It is a very sensitive tumour and chemo-radiotherapy provides an excellent local efficiency (80%); the 5 years survival rates is about 50%.

Randomized trial of neoadjuvant chemotherapy in oropharyngeal carcinoma. French Groupe d'Etude des Tumeurs de la Tête et du Cou (GETTEC).

The objective of the study was to evaluate the effect of neoadjuvant chemotherapy on the survival of patients with oropharyngeal cancer. Patients with a squamous cell carcinoma of the oropharynx for whom curative radiotherapy or surgery was considered feasible were entered in a multicentric randomized trial comparing neoadjuvant chemotherapy followed by loco-regional treatment to the same loco-regional treatment without chemotherapy. The loco-regional treatment consisted either of surgery plus plus radiotherapy or of radiotherapy alone. Three cycles of chemotherapy consisting of Cisplatin (100 mg/m2) on day 1 followed by a 24-hour i.v. infusion of fluorouracil (1000 mg/m2/day) for 5 days were delivered every 21 days. 2-3 weeks after the end of chemotherapy, local treatment was performed. The trial was conducted by the Groupe d'Etude des Tumeurs de la Tête Et du Cou (GETTEC). A total of 318 patients were enrolled in the study between 1986 and 1992. Overall survival was significantly better (P = 0.03) in the neoadjuvant chemotherapy group than in the control group, with a median survival of 5.1 years versus 3.3 years in the no chemotherapy group. The effect of neoadjuvant chemotherapy on event-free survival was smaller and of borderline significance (P = 0.11). Stratification of the results on the type of local treatment, surgery plus radiotherapy or radiotherapy alone, did not reveal any heterogeneity in the effect of chemotherapy.

[Midface reconstruction with free flaps]. / Reconstruction de l'étage moyen de la face par transplants libres.

STUDY AIM: Midface is situated between the occlusal plane and the transverse midorbital plane. The aim of midface reconstruction is to restore the bony and soft tissue contour of the face, to obtain a rigid support for the velum, to allow oronasal separation, and to allow support for the orbit and obliteration of the maxillary sinus in order to restore the main functions: respiration, speech, deglutition, mastication, olfaction, vision. PATIENTS AND METHODS: Between 1988 and 1997, 65 patients with defects to the midface in relation with cancer (n = 60), gunshot (n = 3), or congenital malformation (n = 2), underwent reconstruction with one or more transplants: forearm (n = 21), latissimus dorsi (n = 23), scapula (n = 12), composed subscapula (n = 10), and fibula (n = 4). Forty-seven of the patients were men and 18 were women. The mean age was 56 years (12-90 years). In patients with cancer, tumoral resection was immediately followed by midface reconstruction in the last 43 cases. Free flaps were selected for reconstruction of each part of the midface: cheek, nose, orbit floor, maxillary and palate. RESULTS: One post-operative death occurred (1.5%). The morbidity rate (18.7%) included necrosis of the free flaps in four cases. Average resumption of oral intake was ten days. The mean time to discharge was 17 days. Aesthetic and functional results were rated good or excellent in 53 patients. After one year, 52 patients were alive. Oral intake was normal in 48 patients, and mixed in four. Speech was excellent or good in 49 patients. From amongst the patients, 80% were able to find a job. CONCLUSION: Free flaps with micro surgery provides an optimal, functional, morphological and aesthetic outcome. Patients with advanced cancer of the midface are best managed through a multidisciplinary team approach. Microsurgical reconstruction represents the technical state of the art in case of extensive and complex midface defect.

[Primary synovial sarcoma of head and neck. Materials of The Gustave Roussy Institute. Report of 13 cases]. / Synovialosarcomes cervico-faciaux. Expérience de 1'Institut Gustave Roussy. A propos de 13 cas.

This report presents the result of our experience with 13 primary synovial sarcoma of the head and neck. The 9 males and 4 females had a median age of 32 years. The predominant location of the tumor was the pharynx, treatment consist of surgical excision alone or associated with post-operative radiotherapy or chemotherapy. Mean follow-up was 48 month. Local recurrence occurred in 2 patient, 4 patient died of pulmonary metastasis. The five year survival rate was 55%. Favorable prognostic findings included age < 20 years and complete initial resection.

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.

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.

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.

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.

[Isolated mandibular metastasis of cancer of the thyroid. Mandibulectomy and reconstruction using a free vascularized peroneal graft]. / Métastase mandibulaire isolée d'un cancer de la thyroïde. Mandibulectomie et reconstruction par un transplant libre de péroné vascularisé.

Isolated mandibular metastasis from a thyroid cancer is exceptional. In our observation, it was revealed 13 years after the thyroid cancer (papillo-vesicular carcinoma which was treated with total thyroidectomy, nodes resection and I 131). Treatment included interruptive mandibulectomy and reconstruction with a free composed vascularized fibular transplant. Follow-up was uneventful. Functional and morphological results were excellent. Isolated cases are reported in the literature. Surgical resection must be achieved. The originality of our observation is the mandibular reconstruction with a free vascularized fibular transplant.