Wrapping Up Hydrophobic Hydration: Locality Matters.

Water, being the universal solvent, acts as a competing agent in fundamental processes, such as folding, aggregation or biomolecular recognition. A molecular understanding of hydrophobic hydration is of central importance to understanding the subtle free energy differences, which dictate function. Ab initio and classical molecular dynamics simulations yield two distinct hydration water populations in the hydration shell of solvated tert-butanol noted as "HB-wrap" and "HB-hydration2bulk". The experimentally observed hydration water spectrum can be dissected into two modes, centered at 164 and 195 cm-1. By comparison to the simulations, these two bands are attributed to the "HB-wrap" and "HB-hydration2bulk" populations, respectively. We derive a quantitative correlation between the population in each of these two local water coordination motifs and the temperature dependence of the solvation entropy. The crossover from entropy to enthalpy dominated solvation at elevated temperatures, as predicted by theory and observed experimentally, can be rationalized in terms of the distinct temperature stability and thermodynamic signatures of "HB-wrap" and "HB-hydration2bulk".

Cation-specific interactions of protein surface charges in dilute aqueous salt solutions: a combined study using dielectric relaxation spectroscopy and Raman spectroscopy.

We exploited glycine as a zwitterionic model system to experimentally probe the cation specific interaction of protein surface charges in dilute (≤0.25 mol L-1) aqueous solutions of four biologically relevant inorganic salts, NaCl, KCl, MgCl2 and CaCl2, via dielectric relaxation spectroscopy (DRS) and Raman spectroscopy. Glycine is the simplest building block of proteins and it exposes the same charged groups (carboxylate and ammonium) to the solvent that dominate the protein-water interface. As a counter ion, we selected Cl- due to its biological importance. For all systems, we performed simultaneous fitting of the real (ε') and imaginary (ε″) parts of the dielectric functions, assuming a multimodal relaxation model, obtained from concentration dependent dielectric measurements at ∼293 K. We observe a reduction of the dielectric amplitude for the glycine relaxation while the corresponding time constant shows only small (<7%) deviations compared to aqueous glycine solutions. We propose that the observed reduction in dielectric amplitude is due to a reduction of the effective dipole moment (µeff) of zwitterionic glycine caused by the interaction of glycine with the ion even at very low (0.05 M) salt concentrations. The interaction between divalent metal ions and zwitterionic glycine is increased compared to the monovalent cation-zwitterion interaction; a finding that is also supported by Raman spectroscopy. Our combined dielectric relaxation and Raman spectroscopic study indicates that ion-glycine interactions are weak and mediated by the solvent. Cation-specificity of protein surface charges is also observed in dilute salt solutions (≤0.25 mol L-1), where electrostatic interactions dominate.

Observation of rovibrational transitions of HCl, (HCl)2, and H2O-HCl in liquid helium nanodroplets.

We report the infrared spectra of HCl, (HCl)2, and H2O-HCl in liquid helium nanodroplets in the frequency region between 2680 and 2915 cm(-1). For the HCl monomer a line width of 1.0 cm(-1) (H35Cl) corresponding to a lifetime of 5.3 ps was observed. The line broadening indicates fast rotational relaxation similar to that previously observed for HF. For (HCl)2 the free HCl as well as the bound HCl stretching band has been observed. The nu2+ bands of (HCl)2 could be rotationally resolved, and rotational constants were deduced from the spectra. We observed both the allowed and the symmetry forbidden transition. However, the forbidden "broken symmetry" tunneling transition of the mixed dimer shows an intensity that is considerably enhanced compared to the gas phase. Upon the basis of the present measurements we were able to calculate the tunneling splitting in the excited state. The tunneling splitting is found to be reduced by 28% compared to the gas phase. Transitions from the ground state to the Ka=1 level of the free HCl stretch (nu1) are recorded and show considerable line broadening with a line width of 2 cm(-1). The excited state Ka=1 has an additional rotational energy of about 10 cm(-1), thereby allowing fast rotational relaxation by coupling to helium excitations. In addition we observed the HCl stretch of the HCl-H2O dimer, which exhibits an unusually large width (1.7 cm(-1) for H35Cl)) and large red shift (8.5 cm(-1)), compared to the gas-phase values. The large-amplitude motion originating from the libration mode of the HCl-H2O complex is supposed to act as a fast relaxation manifold.

Solute-induced retardation of water dynamics probed directly by terahertz spectroscopy.

The dynamics of water surrounding a solute is of fundamental importance in chemistry and biology. The properties of water molecules near the surface of a bio-molecule have been the subject of numerous, sometimes controversial experimental and theoretical studies, with some suggesting the existence of rather rigid water structures around carbohydrates and proteins [Pal, S. K., Peon, J., Bagchi, B. and Zewail A. H. (2002) J. Phys. Chem. B 106, 12376-12395]. Hydrogen bond rearrangement in water occurs on the picosecond time scale, so relevant experiments must access these times. Here, we show that terahertz spectroscopy can directly investigate hydration layers. By a precise measurement of absorption coefficients between 2.3 THz and 2.9 THz we could determine the size and the characteristics of the hydration shell. The hydration layer around a carbohydrate (lactose) is determined to extend to 5.13 +/- 0.24 A from the surface corresponding to approximately 123 water molecules beyond the first solvation shell. Accompanying molecular modeling calculations support this result and provide a microscopic visualization. Terahertz spectroscopy is shown to probe the collective modes in the water network. The observed increase of the terahertz absorption of the water in the hydration layer is explained in terms of coherent oscillations of the hydration water and solute. Simulations also reveal a slowing down of the hydrogen bond rearrangement dynamics for water molecules near lactose, which occur on the picosecond time scale. The present study demonstrates that terahertz spectroscopy is a sensitive tool to detect solute-induced changes in the water network.

[Pediatric rhabdomyosarcoma of the infratemporal fossa]. / Les rhabdomyosarcomes de la fosse infratemporale de l'enfant.

OBJECTIVE: Prognosis of rhabdomyosarcoma of the infratemporal fossa is generally poor. We report our experience. MATERIAL AND METHODS: Twenty-three children with rhabdomyosarcoma of the infratemporal fossa were treated at the Gustave Roussy and Curie Institutes between 1984 and 1999. Seventeen children received radiotherapy (group 1), four children were treated surgically with or without postoperative radiotherapy (group 2), and two children received no further treatment after chemotherapy (group 3). RESULTS: In group 1, there were 10 local recurrences and one metastatic failure; all 11 children died from their disease. Nodal recurrence was salvaged successfully in one other with chemotherapy and surgery. In group 2, three children were disease free at 3 years and one died of local recurrence. In group 3, one child experienced a local recurrence successfully salvaged with radiotherapy. This child was disease free at 3 years. The other child developed local recurrence and died. DISCUSSION: Overall survival rate in our patients was 50%. Local control remained the main prognostic factor for survival. Surgery has already been shown to improve local control in other localizations of rhabdomyosarcoma. If residual tumor tissue remains after neo-adjuvant chemotherapy, surgery should be considered in a multidisciplinary discussion of therapeutic options. Indications for postoperative radiotherapy depend on age and histological features of the surgical specimen.

[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.

Early locoregional high-dose radiotherapy is associated with long-term disease control in localized primary angiocentric lymphoma of the nose and nasopharynx.

Nasal NK/T cell is a rare form of usually localized non-Hodgkin's lymphoma (NHL) which generally carries a poor prognosis when treated with conventional NHL chemotherapy protocols. We reviewed 20 consecutive localized stage I/II nasal NK/T cell lymphomas treated at our institution over a 29 year period. Median age was 44 (range 23-71). Front-line therapy was generally radiotherapy alone (35-70 Gy) before 1980 and combination chemotherapy after 1980. Six patients were treated with first-line radiotherapy and they achieved complete remission (CR). Two subsequently received combination chemotherapy. Five of those patients remained in complete remission, after 97+ to 277+ months. Twelve patients were treated with first-line chemotherapy including CHOP or CHOP-like regimen in seven cases, and COP in five cases. Only three of them achieved CR, five had partial response and four had progressive disease. Five of the seven patients treated with CHOP did not achieve complete remission. The nine patients who failed to achieve CR with chemotherapy subsequently received salvage radiotherapy but only two of them obtained CR. Finally, two patients were treated with alternated chemotherapy and radiotherapy and achieved CR, which persisted after 14+ and 26+ months. Median survival was not reached in patients who received front-line radiotherapy, and was 35 months in patients who received front-line chemotherapy. These findings confirm that chemotherapy gives a low complete remission rate in localized nasal NK/T cell lymphoma. By contrast, first-line radiotherapy seems to give favorable results, whereas its results are poorer when administered after resistance to chemotherapy. Whether the use of chemotherapy after radiotherapy, or alternated chemotherapy-radiotherapy regimens give better clinical results than radiotherapy alone will have to be evaluated prospectively in this type of NHL.

Synovial sarcomas of the head and neck: CT and MR imaging findings of eight patients.

BACKGROUND AND PURPOSE: Synovial sarcomas are soft-tissue tumors that rarely occur in the head and neck. The purpose of this study was to evaluate their CT and MR imaging appearance and to show that they may have a surprisingly benign imaging appearance. METHODS: Eight patients with histologically proved synovial sarcoma underwent CT; additionally, MR imaging examinations were performed in five of the eight cases. Attenuation and signal intensity on CT scans and MR images, respectively, were studied by two radiologists. They analyzed the location, size, margins, homogeneity, presence of adenopathies and infiltrative signs, and enhancement after injection of contrast medium. RESULTS: Four tumors were located in the hypopharynx, two arose from the infratemporal fossa, one arose from the maxillary sinus, and one arose from the faucial tonsil. Tumor sizes ranged from 27 to 70 mm. On CT scans and MR images, six lesions were homogeneous and well defined, with smooth margins. The remaining tumors were heterogeneous. In two cases, adjacent tissues were invaded. Calcifications were observed in one case and adenopathy in two cases. In three cases, the lesions were isointense on T1-weighted MR images and hypointense on T2-weighted MR images, and in the other two cases in which MR imaging was performed, the lesions were both isointense and hypointense on both T1- and T2-weighted images. Only the two local recurrent lesions were multilocular. CONCLUSION: Synovial sarcomas are aggressive sarcomas that may appear "benign" in some cases. In a young man, a synovial sarcoma may be suspected when a well-demarcated, homogeneous lesion is found in the head and neck.

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.

Subcranial fronto-orbito-nasal approach for ethmoidal cancers surgical techniques and results.

BACKGROUND: The authors report their experience with the subfronto-orbito-nasal approach (SFON) for the treatment of 30 patients suffering from ethmoidal cancers over the past 3 years. The advantages and pitfalls of this technique are described and compared with other classic approaches. METHODS: Among 156 patients suffering from ethmoidal cancers and treated between January 1984 and January 1998, 30 patients were operated on using the SFON approach during the past 3 years. There were 27 males and 3 females, ranging in age from 15 to 77 years. Histologic composition of the lesions was as follows: 15 adenocarcinomas, 6 esthesioneuroblastomas, 3 melanomas, 2 epidermoid carcinomas, 1 nondifferentiated carcinoma, 1 neuroendocrine carcinoma, 1 villous carcinoma, and 1 cystic adenoid carcinoma (cylindroma). According to the authors' classification, 7% were T1, 6% T2, 22% T3, 38.5% T4a, and 26.5% T4b. All patients were operated on through a SFON approach, followed by removal of the tumor and reconstruction of the skull base with a pericranial flap. RESULTS: Since the mean follow-up was of short duration (12 months, ranging from 3 to 29 months), significant carcinologic results could not be obtained. However, a detailed analysis of the surgical procedure was performed. No patient died or had major complications related to the SFON approach. One cerebrospinal fluid (CSF) fistula and four oculomotricity dysfunctions were observed. Definitive anosmia was reported in all cases. CONCLUSION: The advantages of the procedure include a wide exposure of the anterior skull base through a limited approach, the possibility of modifying the approach according to the size and location of the lesion, total resection of tumors, simplified skull base reconstruction technique, and reduction of postoperative confusion and hospital stay.

[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.

Extramedullary solitary plasmacytoma of the head and neck. A clinicopathological study.

Monoclonal extramedullary plasmacytoma (EMP) is a rare, low-grade lymphoma found predominantly in the head and neck region. Only since the introduction of immunophenotyping techniques 2 decades ago has it been possible to differentiate EMP from benign polyclonal plasma cell proliferation. The purpose of this study was to trace the evolutionary profile of the disease under consideration of monoclonality assessment. The records of 24 patients with morphologically diagnosed EMP treated in a single institution underwent clinical and pathological review. Only 14 patients had true monoclonal plasmacytoma. No EMP-related deaths occurred. Two patients had local recurrence, and 2 patients developed multiple myeloma. Review of the literature confirms the low-grade malignancy of EMP. Diagnostic procedures must exclude benign polyclonal plasmacytoma, multiple myeloma, and solitary bone plasmacytoma. The slow natural progression of the disease and the rarity of secondary multiple myeloma favor nonmutilating local surgery whenever possible to avoid the long-term sequelae of radiotherapy.

Percutaneous gastrostomy with fluoroscopic guidance: single-center experience in 500 consecutive cancer patients.

PURPOSE: To evaluate the feasibility, complications, adequacy of feeding support, and tolerability of fluoroscopically guided gastrostomy in cancer patients. MATERIALS AND METHODS: Five hundred cancer patients were referred for fluoroscopically guided gastrostomy, among whom percutaneous endoscopic gastrostomy was contraindicated or had been unsuccessful in approximately one-fourth. Five hundred eight fluoroscopically guided gastrostomies with T-fastener gastropexy were performed in 496 patients. The procedure was unsuccessful in four patients, and 12 patients needed a second gastrostomy. RESULTS: Fluoroscopically guided gastrostomy was feasible in 99% of patients. During the first 30 postprocedure days, there were seven major complications (1.4%): cardiac failure (n = 1), hemorrhage (n = 1), and peritonitis (n = 5); one patient died of peritonitis. No major complications occurred after the 30th postprocedure day. There were 27 minor complications (5.4%) during the first 30 postprocedure days and 88 (17.6%) thereafter. Long-term minor complications mainly involved the disturbances and nearly always resolved once the tube was exchanged. Such exchanges were easily performed under fluoroscopic guidance except in two patients, who required repeat fluoroscopically guided gastrostomy. CONCLUSION: Fluoroscopically guided gastrostomy is highly feasible and safe and provides adequate feeding support, even when percutaneous endoscopic gastrostomy is impossible. Long-term complications, which are mainly tube disturbances, are easily treated.

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.