Search

The aim of this study is to show that surgical treatment of early-stage squamous cell carcinomas of the oropharynx gives identical, if not better, oncological results than the classic radiotherapy treatment in terms of locoregional control and survival. Fifty-three patients (32 T1, 21 T2, all N0) were operated on during the years 1995-2000. Surgical treatment consisted in a resection by the transoral approach in 43 patients (81.13%); ten patients (18.87%) benefited from a pharyngectomy with (seven) or without (three) mandibular resection. A level I to V selective neck dissection was performed on 35 patients, and 5 patients underwent a level II to V selective neck dissection. The 1-, 3- and 5-year overall survival rates were 100, 94.6 and 73%, respectively. There was no significant difference concerning the tumor stage ( P=0.69), the initial localization ( P=0.64), the macroscopic aspect ( P=0.65) and the management undertaken in the different centers ( P=0.19). The 5-year rate of specific survival was 100%. The 1-, 3- and 5-year locoregional control rates were 96.22, 92.45 and 88.68, respectively. The oncological occurrences observed were 2 persistent diseases, 5 local recurrences, 11 second primary cancers and 0 nodal recurrences. Seven local failures were observed, all of which were controlled after a second treatment. Eleven patients presented second primary cancers; three died, two are alive with an extension of this second localization, and six are alive and free of disease. The locoregional control provided by surgery alone on T1-T2 N0 oropharyngeal cancers is as good as radiotherapy. Moreover surgery alone makes it possible to spare patients the complications and aftereffects of radiotherapy. It also makes it possible during the recurrences to operate on patients in non-irradiated areas with lower morbidity and mortality. It is all the more beneficial since it will be possible to resort to radiotherapy after surgery if need be.

5-HT(2) receptors mediate a large array of physiological and behavioral functions in humans via three distinct subtypes: 5-HT(2A), 5-HT(2B)and 5-HT(2C). While selective 5-HT(2A)antagonists have been known for some time, knowledge of the precise role played by the 5-HT(2B)receptor was hampered by the existence of solely 5-HT(2B)5-HT(2C) mixed antagonists. However, selective 5-HT(2B)antagonists began recently to emerge in the literature. Indeed, four structural classes belonging to the piperazine, indole, naphthylpyrimidine and tetrahydro-beta-carboline scaffolds were reported. In this paper, we will briefly review the structural and pharmacological features of selective 5-HT(2B) antagonists, including patent literature of the last five years.

Objective: This study reviews a rare and poorly understood anatomic anomaly of the thyroid region: non-recurrence of the inferior laryngeal nerve., Method: We describe thirteen cases of non-recurrence of the laryngeal nerve observed during 2128 surgical procedures on the thyroid gland., Results: The malformation was right-sided in all thirteen patients (11 women, 2 men) and occurred at a frequency of 0.4% of all of the nerves explored. Only two complications were noted in this series of 13 cases: one case of temporary paresis and one case of irreversible vocal cord paralysis., Conclusion: A rare although not exceptional occurrence, non-recurrence of the inferior laryngeal nerve is an anomaly that Head and Neck surgeons should be familiar with so as to avoid nerve damage that can result in irreversible vocal cord paralysis.

Objectives: The larynx is an unusual localization for schwannoma. We present a case report and review pertinent data in the literature., Material and Methods: Laryngeal schwannoma was discovered in a 56-year-old woman who complained of persistent dysphonia. We present the histological findings leading to diagnosis and radiological data together with the therapeutic surgical procedure., Results: There was no postoperative complication and functional outcome was excellent at one year follow-up, demonstrating that conservative surgery is required for this type of disease., Conclusion: Computed tomography and magnetic resonance imaging provide essential data on the spread of this benign submucosal tumor for optimal resection. Conservative surgery provides excellent results.

Employing a novel, rapid and sensitive method for evaluation of phospholipase C (PLC) activity, the present study characterized the actions of diverse agonists and antagonists at human (h)5-HT2C receptors expressed in Chinese Hamster Ovary (CHO) cells. In addition, affinities and efficacies at these sites were compared with those obtained at h5-HT2B receptors.5-HT elicited a robust and rapid reduction in levels of the pre-labelled, membrane-bound substrate of PLC, [3H]phosphatidylinositols ([3H]PI). The time-course of [3H]PI depletion paralleled that of [3H]inositol phosphate ([3H]IP) accumulation, as determined by conventional anion exchange chromatography. Inactivation of h5-HT2C receptors with the alkylating agent, N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), revealed a large receptor reserve, with half-maximal PLC activation induced by a concentration of 5-HT occupying only 5% of sites. In analogy to 5-HT ( Emax=100%), DOI, MK212 and mCPP, as well as the novel ligands, Ro600332, Ro600175 and BW723C86, showed "full" efficacy at h5-HT2C sites. Their efficacies were similar at h5-HT2B sites, with the exception of mCPP and MK212, which acted as partial agonists. Further, lisuride and Ro600869 behaved as partial agonists and antagonists at h5-HT2C and h5-HT2B receptors, respectively. As concerns functional selectivity (potency for induction of [3H]PI depletion), only Ro600175 preferentially activated h5-HT2B sites. In contrast, Ro600332 preferentially activated h5-HT2C receptors. Amongst antagonists, RS102221 and SB242084 displayed a marked preference for h5-HT2C sites, whereas LY266097, S33526 and SB204741 behaved as selective antagonists at h5-HT2B receptors. At both h5-HT2C and h5-HT2B receptors, antagonist potency (p Kb) and binding affinity (p Ki) were highly correlated. In conclusion, this rapid and innovative method for determination of PLC activity permitted characterization of an extensive range of novel ligands at h5-HT2C receptors. Although several antagonists clearly differentiated h5-HT2C from h5-HT2B receptors under these conditions, highly selective agonists remain to be identified.

The larynx as a site of tuberculosis represents less than 1% of the total of this disease. Primary tuberculous laryngitis is even more rare. The authors report a case of an 89 year-old man presenting with swallowing disorders (dysphagia and overspill) consulting for suspected laryngeal carcinoma. Finally, the diagnosis was laryngeal tuberculosis. The outcome was favourable with appropriate treatment, obtaining complete healing without any after-effects. The diagnosis of tuberculosis must cross the clinician's mind, even when there are no general symptoms.

Purpose: Patients suffering from locally advanced unresectable squamous cell carcinoma of the oropharynx and hypopharynx treated with radiotherapy alone have a poor prognosis. More than 70% of patients die within 5 years mainly due to local recurrences. The aim of this study was to evaluate retrospectively the Antoine Lacassagne Cancer Center's experience in a treatment by concomitant bid radiotherapy and chemotherapy. Evaluation was based on analysis of the toxicity, the response rates, the survival, and the clinical prognostic factors., Patients and Methods: From 1992 to 2000, 92 consecutive patients were treated in our single institution. All of them had stage IV, unresectable squamous cell carcinoma of the pharynx and they received continuous bid radiotherapy (two daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal interval between fractions). Total radiotherapy dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Two or three chemotherapy courses of cisplatin (CP)-5-fluorouracil (5FU) were given during radiotherapy at 21-day intervals (third not delivered after the end of the radiotherapy). CP dose was 100 mg/m2 (day 1) and 5-FU was given as 5-day continuous infusion (750 mg/m2/day at 1st course; 430 mg/m2/day at 2nd and 3rd courses). Special attention was paid to supportive care, particularly in terms of enteral nutrition and mucositis prevention by low-level laser energy., Results: Acute toxicity was marked and included WHO grade III/IV mucositis (89%, 16% of them being grade IV), WHO grade III dermatitis (72%) and grade III/IV neutropenia (61%). This toxicity was significant but manageable with optimised supportive care, and never led to interruption of treatment for more than 1 week, although there were two toxic deaths. Complete global response rate at 6 months was 74%. Overall global survival at 1 and 2 years was 72% and 50% respectively, with a median follow-up of 17 months. Prognostic factors for overall survival were the Karnofsky index (71% survival at 3 years for patients with a Karnofsky index of 90-100% versus 30% for patients with a Karnofsky index of 80% versus 0% for patients with a Karnofsky index of 60-70%, p = 0.0001) and tumor location (55% at 3 years for oropharynx versus 37% for panpharynx versus 28% for hypopharynx, p = 0.009)., Conclusion: These results confirm the efficacy of concomitant bid radiotherapy and chemotherapy in advanced unresectable tumor of the pharynx. The improvement in results will essentially depend on our capacity to restore in a good nutritional status the patients before beginning this heavy treatment.

Purpose of the Study: We analyzed our experience with the cervical platysma myocutaneous flap and reviewed the pertinent literature. We evaluated the harvesting technique, surgical indications, reliability of the flap, its advantages and drawbacks compared with other reconstruction techniques and assessed survival and local control., Materials and Methods: This retrospective series included 70 patients with a mean 83-month follow-up. All patients had an oral cavity or oropharyngeal carcioma ranging from T1 to T4, N0 to N2b according to the TNM classification. All underwent one-step surgery with unilateral or bilateral type III elective neck dissection, followed by tumor resection, and reconstruction with a cervical platysma myocutaneous flap., Results: Complications related to flap reliability were observed in 17 cases (24.3%): 1 total necrosis (1.4%), 6 partial necrosis (8.6%), and 10 paddle epidermolysis (14.3%). Median survival and local control were 35 and 59 months respectively. Eight out of 55 preoperative N0 patients were histologically N+ (14.5%). No significant difference in risk of metastasis recurrence was evidenced between N0 and N+ patients (p > 0.05)., Discussion: Reconstruction after ablation of oral or oropharyngeal cancer using a cervical platysma myocutaneous flap can be easily combined with an elective neck dissection without increasing the risk of recurrence. The flap must preserve the facial artery and its submental branch and the external jugular vein to ensure reliability. When indications are strictiy applied, the properties of the platysma plasty and the anterolateral cervical situation provide very satisfactory functional and esthetic results.

The aim of this retrospective study was to evaluate the cost and benefit of percutaneous fluoroscopic gastrostomy feeding (PFG) in 70 cancer patients with advanced stage disease of the upper-aero digestive tract; we retrospectively analyzed the consequences in terms of nutritional status (evaluated by weight and body mass index), the possibility to lead a treatment by high dose chemo-radiotherapy to the end of the therapeutic schedule, the feasibility, complications and cost ratios. Three weeks after the procedure, no major complication was observed, the initial nutritional threshold was conserved. PFG is a safe and effective technique; the additional cost is low (2%) compared with the total cost of hospitalization.

Pre operative and per-operative suspicion, and recognition of parathyroid carcinoma are essential in the effective approach and the prognosis of this type of tumor. On the basis of our experience over 20 years, helped by the literature we review our 179 cases of primary hyperparathyroidism out of which 5 were malignant tumors and the 174 others were benign (adenomas and hyperplasias). We conclude that patients with primary hyperparathyroidism, reflected by high levels of serum calcium (75%) and elevated levels of parathormone (100%) are suspect of carrying a parathyroid malignancy particularly when these levels are profoundly abnormal. Furthermore, a severe clinical presentation featuring, palpable cervical mass, renal symptoms in 30% to 60% of all, bone disease in 90%, is suspect of malignancy. The operative findings such as important size of tumour, local seeding, local invasion are also significant features of malignancy. All this data gathered by comparing carcinomas to adenomas suggest and confirm what many reviews on the subject have reported, early recognition of the parathyroid carcinoma is of primal importance, because aggressive initial surgical management should be applied, as total extirpation of the malignancy is the only treatment allowing maximal survival rates.

Use of the low-energy helium-neon laser (LEL) appears to be a simple atraumatic technique for the prevention and treatment of mucositis of various origins. Preliminary findings, and significant results obtained for chemotherapy-induced mucositis in a previous phase III study, prompted a randomized multicenter double-blind trial to evaluate LEL in the prevention of acute radiation-induced stomatitis. Irradiation by LEL corresponds to local application of a high-photon-density monochromatic light source. Activation of epithelial healing for LEL-treated surfaces, the most commonly recognized effect, has been confirmed by numerous in vitro studies. The mechanism of action at a molecular and enzymatic level is presently being studied. From September 1994 to March 1998, 30 patients were randomized. Technical specification: 60 mW (25 mW at Reims, 1 patient), He-Ne, wavelength 632.8 nm. The trial was open to patients with carcinoma of the oropharynx, hypopharynx and oral cavity, treated by radiotherapy alone (65 Gy at a rate of 2 Gy/fraction, 5 fractions per week) without prior surgery or concomitant chemotherapy. The malignant tumor had to be located outside the tested laser application areas (9 points): posterior third of the internal surfaces of the cheeks, soft palate and anterior tonsillar pillars. Patients were randomized to LEL or placebo light treatment, starting on the first day of radiotherapy and before each session. The treatment time (t) for each application point was given by the equation : t(s)= energy (J/cm2) x surface (cm2)/Power (W). Objective assessment of the degree of mucositis was recorded weekly by a physician blinded to the type of treatment, using the WHO scale for grading of mucositis and a segmented visual analogue scale for pain evaluation. Protocol feasibility and compliance were excellent. Grade 3 mucositis occured with a frequency of 35.2% without LEL and of 7.6% with LEL (P<0.01). The frequency of "severe pain" (grade 3) was 23.8% without LEL, falling to 1.9% with LEL (P<0.05). Pain relief was significantly reduced throughout the treatment period (weeks 2-7). LEL therapy is capable of reducing the severity and duration of oral mucositis associated with radiation therapy. In addition, there is a tremendous potential for using LEL in combined treatment protocols utilizing concomitant chemotherapy and radiotherapy.

Background: Pedicled myocutaneous flaps remain important tools in head and neck reconstruction. Evaluation of their complications are necessary to judge their merits., Methods: From 1985 to 1995, 44 patients underwent a myocutaneous platysma flap reconstruction of the oral cavity or oropharynx. The following potential risk factors for complications were analyzed: age, sex, site of primary tumor, TNM stage, previous treatment, neoadjuvant chemotherapy, and type of operation., Results: Flap-related complications occurred in 18 patients. Only one patient required reoperation for flap failure. Nineteen minor complications occurred in 17 patients. A significant increase in complications was seen in patients in which neoadjuvant chemotherapy was given., Conclusions: One flap failure was observed in our series. As the platysma flap has several advantages, it should be considered in the reconstruction of small intraoral defects. Contraindications are previous radiotherapy and surgery in the head and neck, neoadjuvant chemotherapy, nodal disease, and large defects.

Purpose: The aim of this phase II study conducted on unresectable squamous cell carcinoma (USCC) of the oro- and hypopharynx was to associate twice-a-day (b.i.d.) continuous nonaccelerated radiotherapy with concomitant cisplatin (CP)-5-fluorouracil (5-FU) chemotherapy, both given at full dose. Feasibility, efficacy, survival, and pharmacokinetic-pharmacodynamic relationships were analyzed., Methods and Materials: Fifty-four consecutive patients with strictly USCC of oro- and/or hypopharynx received continuous b.i.d. radiotherapy (RT) (2 daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal interval between fractions). Total RT dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Three chemotherapy (CT) courses of CP-5-FU were given during RT at 21-day intervals (third not delivered after the end of RT). CP dose was 100 mg/m2 (day 1) and 5-FU was given as 5-day continuous infusion (day 2-day 6: 750 mg/m2/day cycle 1, 750 mg total dose/day cycle 2 and 3). Pharmacokinetics was performed for 5-FU (105 h follow-up) and CP (single sample at 16 h). Special attention was paid to supportive care., Results: Good feasibility of RT was observed (85.2% of patients with total dose > 75 Gy). Five patients received 1 CT cycle, 34: 2 cycles, and 15: 3 cycles. The most frequent and severe acute toxicities were mucositis with grade 3-4 occurring in 28% at cycle 1 and 86% at cycle 2, as well as neutropenia (43% at cycle 2). Locoregional control at 6 months was observed in 66.7% of patients. No late toxicity above grade 2 RTOG was noticed. CP dose and 5-FU AUC(0-105h) were significantly linked to grade 3-4 neutropenia (cycle 2). Cumulative total platinum (Pt) concentration and Karnofsky index were the only independent predictors of locoregional control at 6 months. Finally, total RT dose and total Pt concentration were the only independent predictors of specific survival., Conclusion: This protocol showed good locoregional response with an acceptable toxicity profile. Pharmacokinetic survey is probably an effective approach to further reduce toxicity and improve efficacy. A multicentric randomized phase III study, now underway, should confirm these encouraging results.

Malignant melanoma with primary onset in the nasal cavity and paranasal sinuses remains a scarcely encountered malignancy and we report 12 cases of our own experience from 1991. These mucosal melanomas occur mainly in the elderly and present most commonly as a one sided airway obstructive syndrome with often bleeding in the nasal cavity. No sex or race ratio is found. Histological examination of the surgical specimen has been made easier since the use of immunohistochemical studies. The original site of onset is commonly located at the inferior part of the nasal cavity but in many cases, it is noted several sites of tumor localization. Despite well conducted treatment the prognosis remains quite deceiving and significantly poor. In our study, the 4-year actuarial survival was 26%. The 5-year survival rate ranges in the literature from 10% to 40%. Short and long term follow-up show an important rate of recurrence (local and lymph node metastases as well as distant metastases). The insidious evolution of the malignancy usually happens during the first year. Computed tomography and MRI are essential in the evaluation of tumor extension. The treatment is based on the combination of surgery and radiotherapy: Surgery is practised first and must ensure sufficient excision of the tumor without minimal functional or aesthetic damage in this complex region. This surgery is based on surgical approaches to the midface known as Lateral rhinotomy and midfacial degloving. When there is cervical lymph node involvement at the time of diagnosis it is suitable to treat it, even in case of recurrence. Complementary high dose radiation is required to treat tumors which could not undergo surgery and also as adjuvant therapy after removal of the mass.

The authors reviewed a series of 553 consecutive patients who underwent endoscopically guided sinus surgery. Major complications occurred in six patients (2.2%). There was one death due to incorrect positioning of the frontal drain. One patient developed a cerebrospinal fluid leak which had to be closed with an osteomucosal graft. Two patients who developed severe bleeding after removal of the nasal packing, needed ligation of the sphenopalatine artery and the internal maxillary artery, respectively. Two patients developed a complete stenosis of the nasolacrimal duct, necessitating a dacryocystorhinostomy. Minor complications occurred in 36 patients (13.4%). These included damage to the lamina papyracea (n = 11), severe bleeding after removal of the nasal packing treated conservatively (n = 6), intranasal mucosal adhesions (n = 17), and atrophic rhinitis (n = 2). The aetiology, prevention and treatment of complications during and after sinus surgery are also discussed.

Although a remarkable pathology in terms of morbidity and life expectancy, primary hyperparathyroidism remains nonetheless a poorly recognized state despite highly suggestive clinical polymorphism, reliable biological signs and performing imaging for localisation. Through a retrospective study of a series of 129 patients surgically treated for primary hyperparathyroidism over a period of 12 years, helped by a review of the literature, we are able to propose an adapted surgical strategy for every different clinical aspect of this pathology (adenoma, benign hyperplasia, carcinoma). This strategy is guided by specific pre-operative findings and the Sestamibi scintigraphy.

1H-Indolo[3',2':4,5]pyrido[3,2-b]-2-penten-5-olide (6) and 1H,5H-indolo[3',2'-c]-6,7-dihydro-2-pyridone (7), rigid analogues of methyl 4-ethyl-beta-carboline-3-carboxylate (8) and N-methyl-4-ethyl-beta-carboline-3-carboxamide (9), respectively, were synthesized and their in vitro binding affinities to the central type benzodiazepine receptors were compared. The IC50 values of 6 and 8 were approximately equivalent (42 and 27 nM, respectively). The amide derivative 9, for which theoretical energy calculations indicate that the s-trans carbonyl conformation is the preferred one, displayed very low affinity (IC50 greater than 10(4) nM). However, when the carbonyl group of 9 was forced to adopt the s-cis conformation as in lactam 7, binding to the benzodiazepine receptor was largely restored (IC50 = 150 nM), indicating that the s-cis carboxy conformation at C-3 of beta-carbolines is preferentially recognized by this receptor. In vivo, compound 6 showed neither convulsant, proconvulsant, nor anticonvulsant activity in mice. Moreover, 6 did not antagonize methyl beta-carboline-3-carboxylate induced convulsions in mice. This lack of activity of 6 was attributed to its inability to cross the blood-brain barrier since no significant displacement of [3H]Ro 15-1788 from mouse brain benzodiazepine receptors by 6 could be observed in vivo.