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.

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".

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.

High complete response in advanced nasopharyngeal carcinoma with bleomycin, epirubicin, and cisplatin before radiotherapy.

Undifferentiated carcinoma of nasopharyngeal type (UCNT) is a geographically endemic, Epstein-Barr virus-related carcinoma of epidermoid origin with reported 5-year survival rates of 15%-40% when treated with radiotherapy alone. Although UCNT can be well controlled locally by radiation therapy, in advanced nodal stage N3 [International Union Against Cancer-American Joint Committee on Cancer (UICC-AJCC, 1987)] the survival rate is below 20%, primarily because of metastatic spread in 80% of the fatalities. We report a pilot study of 41 patients with nonmetastatic, locoregionally advanced disease (85% of the patients had a nodal status greater than or equal to N2C-N3; 43% had T4 primaries), during which we used a combination of 100 mg of cisplatin/m2 on day 1, 15 mg of bleomycin by intravenous push and 12 mg/m2 by continuous infusion on days 1-5, and 70 mg of epirubicin/m2 on day 1 every 21 days for three cycles before definitive radiation therapy with 70 Gy for 7 weeks. Twenty-seven of 41 patients (66%; 95% confidence interval = 52.5%-80.5%) achieved a clinical complete response, and 40 of 41 (98%) had a major objective response after chemotherapy. Two deaths were treatment related, but side effects were moderate, and the overall treatment sequence was feasible. At the end of radiation therapy, all 39 assessable patients were in complete response, with a median follow-up of 21+ months (greater than 10-greater than 31); 33 (80%) patients had no evidence of disease. We believe that such a complete response rate in a high-volume disease with the use of combined modality treatment indicates a therapeutic gain in UCNT. Researchers performing a multicenter international controlled trial will test this hypothesis and compare local control, disease-free, and overall survival of the therapeutic sequence presented here with radiotherapy alone.

Chemotherapy of metastatic and/or recurrent undifferentiated nasopharyngeal carcinoma with cisplatin, bleomycin, and fluorouracil.

Undifferentiated nasopharyngeal carcinoma (UCNT) is known to be radiosensitive and chemosensitive, but the latter has never been studied prospectively with phase II methodology. After an intensive work-up, 49 patients with recurrent (REC) and/or metastatic (MTS) UCNT were treated with three monthly cycles of cisplatin (CDDP) 100 mg/m2 day 1; bleomycin 15 mg intravenously (IV) day 1, and 16 mg/m2/d continuous infusion (CI) days 1 to 5; and fluorouracil (5FU) 650 mg/m2/d CI days 1 to 5 (PBF). Of the 49 patients, 33 were North African. The sex ratio was three males:one female, and the median World Health Organization (WHO) performance status was 1.6. In the 48 patients assessable for response, we observed nine (19%) complete responses (CRs) and 29 (60%) partial responses (PRs) (60%), for a 79% overall response rate (95% confidence interval, 68% to 90%) in the assessable group and a 78% global rate. There were eight CRs (24%) observed in the group without previous chemotherapy (33 patients) compared with one CR in the chemotherapy pretreated group (16 patients). Four patients are still alive without evidence of disease after 52+, 54+, 58+, and 58+ months, respectively. All of them had less than three bone MTS sites, and received radiation therapy in these sites. The results confirm the chemosensitivity of UCNT, and the observation of unmaintained long-term responders makes curability a possible consideration.

Clinical implications of the serum level of CD23 in patients with undifferentiated nasopharyngeal carcinoma.

PURPOSE: In contrast with other carcinoma cells, cells from nude mice transplanted undifferentiated carcinoma of nasopharyngeal type (UCNT) release the soluble fragment of the CD23 antigen (sCD23). We sought to study the level of sCD23 in sera of untreated UCNT patients. PATIENTS AND METHODS: Pretherapeutic sera from 65 consecutive, locally advanced, initially nonmetastatic UCNT patients were assayed for sCD23. Patients were treated with a neoadjuvant chemotherapy/full-dose radiotherapy sequence. The mean follow-up duration is 50.5 months (range, 28 to 77). The Cox proportional hazards model was used to study the association between sCD23 levels and clinical signs and disease evolution. RESULTS: sCD23 levels showed an association with disease-free survival (DFS; P = .08) and overall survival (OVS; P = .08). Patients with sCD23 levels greater than a cutoff value of 0.6 ng/mL (greater cutoffs were found to be equally significant, but less sensitive), have a relative risk (RR) of relapse of 3.3 (95% confidence interval, 1.6 to 6.9; P = .002), and an RR of death of 2.9 (95% confidence interval, 1.2 to 7.3; P = .02), when taking other prognostic factors into account. CD23 does not correlate with either the response to treatment or the development of metastases, but appears to be related to local control (cutoff, 0.6 ng/mL; RR = 5.1 [95% confidence interval, 1.2 to 21.7]; P = .02). CONCLUSION: The serum level of sCD23 appears to be an independent prognostic factor for initially nonmetastatic, locally advanced UCNT patients, treated with chemotherapy and radiotherapy. Our data indicate an association between this marker and local relapses. Thus, a simple enzyme-linked immunoadsorbent assay (ELISA) could help to identify a high-risk group among nonmetastatic UCNT patients. CD23 could be a marker for two groups of UCNT tumors, with distinct biologic characteristics and clinical behaviors.

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.

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.

Chromosome 11q13 gene amplifications in oral and oropharyngeal carcinomas: no correlation with subclinical lymph node invasion and disease recurrence.

Gene amplifications in the q13 band of chromosome 11 are among the most frequent genetic alterations in head and neck squamous cell carcinomas. Previous studies have suggested that such amplification is a marker of aggressive tumor evolution. Their potential for predicting subclinical lymph node invasion or disease recurrence was investigated in a prospective series of 50 oral and oropharyngeal carcinomas. Cell DNA content was also measured in 32 tumors of this series. Gene amplifications affecting the 11q13 band were detected in 11 of 50 (20%) patients, a relatively low frequency in comparison with data reported previously for other carcinomas of the upper aerodigestive tract, especially hypopharyngeal carcinomas. These gene amplifications were preferentially associated with aneuploidy. Cervical lymph nodes of 26 clinically N0 (Tumor-Node-Metastasis staging) patients were surgically explored. The frequency of 11q13 amplifications was very similar in the presence or in the absence of histological invasion, 3 of 15 (20%) and 2 of 11 (18%), respectively. Thus, 11q13 amplifications do not appear to be a reliable marker for prediction of subclinical lymph-node invasion in oral and oropharyngeal carcinomas. The detection of 11q13 amplifications was also not associated with a higher risk of disease recurrence. These data suggest that not only the prevalence but also the prognostic significance of 11q13 amplifications varies between tumors at different sites in the upper aerodigestive tract.

Alternating chemo-radiotherapy with cisplatin and 5-fluorouracil plus bleomycin by continuous infusion for locally advanced undifferentiated carcinoma nasopharyngeal type.

UNLABELLED: More than 80% of undifferentiated carcinoma nasopharyngeal type patients with N3 disease (AJC-UICC 1987) will die with or from distant metastases within 3 years after the first symptom. From February 1986 to November 1987 30 consecutive patients with very advanced local disease were entered in a programme with chemotherapy-radiotherapy (CT-RT) alternation after a thorough work-up to eliminate the possibility of distant metastases. PROTOCOL: two cycles of cisplatin 100 mg/m2 day 1, bleomycin 15 mg intravenously day 1 and 16 mg/m2 per day by continuous infusion days 1-5; 5-fluorouracil (5-FU) 650 mg/m2 per day by continuous infusion days 1-5 4 weeks apart. This was followed by two series of high-energy radiotherapy, 35 Gy/3.5 weeks, with a third chemotherapy cycle in between. 27 men and 3 women were treated, the median age was 37 years (range 17-71) and the mean WHO performance status was 1 (range 0-3). TNM classification: 15 T4, 9 T3, 6 T2, 28 N3 and 2 N2c. 18 patients had nodes larger than 8 cm and 24 had bulky bilateral cervical nodes. Toxicity for this protocol was moderate, nausea and vomiting being the main side-effects. Results after two CT cycles were 3 complete responses (CR; 10%), 22 partial responses (PR; 73%), 2 disease stabilizations, 2 progressions, and 1 patient inevaluable. Of the 30 patients, 27 patients completed the CT-RT protocol, 2 patients died before radiotherapy and 1 refused treatment after 2 days on protocol. 25 patients were in CR 3 months after the end of radiotherapy. As of August 1991, with a median follow-up of 55 months (range 43-63), there are 17 patients alive, 2 of them with active disease and 15 are NED (2 after salvage therapy).

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.

Twenty years experience of interstitial iridium brachytherapy in the management of soft tissue sarcomas.

From February 1968 to February 1988, 50 patients above 10 years of age with a soft tissue sarcoma were treated with interstitial brachytherapy, combined with a wide excision. After pathologic review, 48 were included in the final analysis. A pathological grading was made possible in 41, which showed a majority of high grades (2 + 3 = 86%). Patients presented mainly with small (less than 5 cm: 36) or mid-size lesions (greater than 5 cm: 12). The tumor was located in the limbs (32), trunk (9), and head and neck (7). Four patients had metastases at the time of treatment. Brachytherapy was part of the initial treatment in 22 cases, and of a salvage procedure after previous excision(s) combined or not with another form of treatment in 26. A uniform technique of iridium 192 wires after-loaded in plastic tubing was used. Sixty Gy median doses were delivered with brachytherapy alone (44) or combined with external beam (4). Sixteen patients also received an adjuvant chemotherapy. Follow up ranged from 16 months to 20 years (median 82 months). At the time of analysis, two patients (4%) only had failed in the irradiated volume, but the marginal failures rate (14:31%) was unexpectedly high. Seven of the patients who failed (43%) were salvaged by a second similar procedure. The 5-year survival was 62% in non-previously treated patients and 56.5% in previously treated ones (pNS). By multivariate analysis, only the tumor location appeared predictive of LF (p less than 0.01), which in turn was strongly correlated with the metastatic outcome (p less than 0.01). Necroses were observed in 17 cases (35%) and associated with a benign course in most of them. High dose brachytherapy combined with conservative surgery is highly effective in small and mid-size soft tissue sarcomas located in the extremities and head and neck, whereas in trunk and in recurrent tumors, the adjunction of large fields external radiotherapy and/or possibly polychemotherapy appears necessary.

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.

Alternating chemotherapy and radiotherapy combination for bulky stage I and II intermediate and high grade non-Hodgkin lymphoma: an update.

In 1980, based on experimental and clinical data, a protocol was developed at the Institut Gustave-Roussy (IGR), alternating eight monthly courses of chemotherapy (CHVP) and two, then three, radiotherapy sequences (15 Gy in 6 fractions and 10 days to the initially involved areas), for early stage unfavourable histology non-Hodgkin lymphomas (NHL). The results are updated for 55 selected patients presenting with bulky stage I and II NHL, intermediate and high grade according to the Working Formulation. Five-year overall survival rate was 69% and freedom from progression was 68%. Early haematologic and digestive tolerance was satisfactory, probably because a 10-15-day interval was respected between chemotherapy and radiotherapy and vice versa. No late toxicity was detected in 39 patients who presented with head and neck localizations; xerostomia was found to be only mild and transient. All patients given mediastinal irradiation experienced radiological mediastinitis, but functional impairment was usually moderate. One of the 4 patients who received 3 x 15 Gy radiotherapy courses to part of the abdomen, died of small bowel obstruction and perforation. The study demonstrated the feasibility of an alternated schedule of chemotherapy and radiotherapy, with satisfactory results in terms of long-term survival. However, the few late complications which were detected after irradiation of the abdomen or of the thorax led to an alteration of the initial scheme when these volumes are to be treated.

Chromosome-11q13 gene amplifications in head and neck squamous-cell carcinomas - relation with lymph-node invasion.

Gene amplifications occurring in the q13 band of chromosome 11 are frequently observed in head and neck squamous cell carcinomas. In order to determine the relative frequency of amplification in 5 distinct 11q13 loci and their relation with clinical data, tumor DNAs from 31 patients - including 26 who had undergone neck dissection (lymph node histology available) - were evaluated by Southern blot. Specific probes were used for the D11S833E, FGF3, CYCD1, D11S97 and GST-pi loci. The most frequently amplified loci were CYCD1 and FGF3 (each locus affected in 17 out of 19 patients with 11q13 amplifications). The range of amplification was from 2x to 9x. Seven (54%) of 13 NO patients had 11q13 amplifications versus 12 (67%) of 18 N1-N3 patients (ns). Among 26 patients for whom lymph node histology was available, 3 (33%) of 9 N- patients had 11q13 amplifications compared to 13 (76%) of 17 N+ patients (p=0.03, G2 test). Fourteen (56%) out of 25 patients staged T>N (for example T4 N1) had 11q13 amplifications versus 5 (83%) of 6 patients N greater-than-or-equal-to T (for example T2 N3) (ns). Of 21 well-differentiated HNSCC, 12 (57%) had 11q13 amplifications versus 7 (70%) of 10 moderately and poorly-differentiated tumors. Three year survival (Kaplan-Meier) was 72.9% for patients without 11q13 amplifications and 44.9% for patients with 11q13 amplifications (ns). Chromosome 11q13 gene amplifications thus appear as a potential prognostic marker, possibly related to loco-regional spread in head and neck squamous cell carcinomas.

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.

Carotid artery obliteration and pharyngoesophageal reconstruction by free jejunal autograft.

Free jejunal autografting is increasingly recognized as a safe procedure of pharyngoesophageal reconstruction with good functional results, following circular total pharyngolaryngectomy for extended tumors of the pharynx or larynx. Very often, past history of irradiation and/or surgery of the neck have created severe atheromatous lesions of the cervical vessels. We report the case of a patient with obliteration of the right carotid artery and large recurrence of a tumor of the larynx in which simultaneous arterial venous bypass and free jejunal autograft were performed for pharyngoesophageal reconstruction.

Synovial sarcoma of the head and neck: an account of four cases and review of the literature.

Four cases of Malignant Synovioma of the head and neck are reported. It is a rare tumour with only 76 published cases in the world literature. Study of these 76 cases allows identification of the clinical features of this tumour and also highlights the problems of histological diagnosis. The study shows that the most effective treatment is radical primary surgery in association with post-operative radiotherapy and chemotherapy.

Surgical salvage treatment of T1/T2 glottic carcinoma after failure of radiotherapy.

PURPOSE: To evaluate the use of conservative surgical salvage techniques (eg, vertical partial laryngectomy and subtotal laryngectomy with cricohyoidopexy) versus total laryngectomy for radiotherapeutic failure of early glottic cancer by retrospective review of medical records. PATIENTS AND METHODS: Of 950 previously untreated endolaryngeal carcinomas managed at the Gustave-Roussy Institute in France between 1975 and 1984, 259 of 344 early glottic cancers (T1, N0 and T2, N0) received radiation therapy. Local failure rates were 14% in T1a cancers, 16% in T1b cancers, and 36% in T2 cancers with normal vocal-cord mobility. RESULTS: Nine of 54 patients with treatment failure were ineligible for salvage surgery. Among the remaining 45 patients, 35 underwent a total laryngectomy; these patients had a 77% 5-year survival rate. Ten patients treated with partial surgery (6 vertical partial laryngectomies and 4 subtotal laryngectomies with cricohyoidopexy) had a 100% survival rate at 5 years. Seven of the 10 patients treated with partial surgery had healing problems that delayed canula and nasogastric tube removal for 30 to 60 days. CONCLUSIONS: Salvage surgery is effective for radiotherapeutic failures of early glottic cancers. In some cases, partial surgery can be performed with good tumor control and satisfactory laryngeal functions. Subtotal laryngectomy is an alternative to total laryngectomy if vertical partial surgery is not suitable.

Rhabdomyosarcoma of the head and neck in adults: a study of 26 patients.

The clinical records of 26, predominantly male, adults with rhabdomyosarcomas in the head and neck were analyzed. Patients' ages ranged from 18 to 74 years (mean: 24.5 years). According to the retrospective clinical group classification, 18 (69%) of 26 were advanced tumors at initial presentation belonging to group III or IV. The ethmoids were the most common primary site of origin in 12 (46%) of 26 patients. Nodal and systemic metastases were noted in 12 (46%) and 6 (23%) patients, respectively. Bone metastases were noted in 4 patients. Heterogeneous treatment protocols were used with a variety of chemotherapy combinations in most cases, with surgery and radiotherapy. Overall results were poor, with a survival rate of 7.6% at 5 years. Neither histopathology nor response to chemotherapy was found to influence survival. All long-term survivors belonged to the early-stage groups (clinical groups I and II) for which complete surgical excision was possible. In spite of a poor prognosis after relapse, the use of aggressive chemotherapy appeared to prolong life in some patients.