Production and significance of CCAAT enhancer binding proteins alpha and beta in sinonasal inverted papilloma.

Sinonasal inverted papilloma (SIP) is a rare benign tumor featuring increased cell proliferation, a tendency toward squamous differentiation, recurrence and malignant transformation. The CCAAT enhancer binding proteins, C/EBPs, are transcription factors regulating the proliferation and differentiation of various types of cells, including epithelial cells. We prospectively investigated the production of these transcription factors and the related proliferation and differentiation targets, keratin-10, keratin-15 and cyclin-D1, in 26 SIP patients and 8 sinonasal polyposis cases suspected for SIP. Ten of these patients had one or more recurrences over follow-up periods of one to eight years. C/EBP-alpha and C/EBP-beta proteins were not found in normal-looking sinonasal epithelial cells. The proteins and RNAs were detected in SIP and, occasionally, in polyposis tissues. The production of these factors was not significantly correlated with age, sex, site, tumor size or medical history. By contrast, correlations were found between the levels of C/EBP-alpha and keratin-10 levels and between those of C/EBP-beta and keratin-15. C/EBP-alpha levels were also significantly correlated with cyclin-D1 levels. These data suggested that the C/EBPs are implicated in the regulation of cell proliferation and differentiation in SIP. Finally, recurrent SIP produced significantly larger amounts of C/EBP-alpha than non- recurrent tumors. These results implicate CCAAT enhancer binding proteins in the pathogenesis of SIP and highlight the role of C/EBP-alpha as a candidate marker for tumor recurrence.

Aberrant beta-catenin and LEF1 expression may predict the clinical outcome for patients with oropharyngeal cancer.

Beta-catenin, normally expressed on the epithelial cell surface, plays a crucial role in cadherin-mediated cell adhesion. Recent evidence suggests that beta-catenin is also involved in other functions such as intracellular signaling via the Wnt pathway by creating a nuclear complex with members of the Lymphoid-Enhancer-Factor/T-Cell-Factor (LEF/TCF) family of transcription factors, and gene regulation that it is implicated in the development of several tumors. Little information is available on beta-catenin expression and its main partner in the Wnt signaling pathway, LEF1, in oropharyngeal squamous cell carcinomas (OP-SCCs). The aim of this study is to investigate the expression of beta-catenin and LEF1 expression in human primary OP-SCCs and to evaluate their clinical and prognostic significance. OP-SCCs and normal peritumoral areas were analyzed by immunohistochemistry, Western-blot and RT-PCR. Beta-catenin was overexpressed in tumors in comparison to normal peritumoral areas and displayed predominantly intracellular (cytosolic/nuclear) localization in 62% of the tumors. Immunoreactivity was correlated with clinicopathological parameters and long-term follow-up, and a significant association was found between protein expression and development of local recurrences (P =0.03). The OP-SCCs with poor clinical outcome, which displayed intracellular beta-catenin expression, were also strongly positive for LEF1, with their co-expression statistically significant (P = 0.040). All (100%) advanced (stages 3+4) SCCs, 66.7% of the SCCs with positive lymph nodes and 80% of the SSCs that developed local recurrences were LEF1 positive. Cox regression analysis confirmed a poorer overall survival in cases with high expression of beta-catenin and LEF1. Our results suggest that assessing intracellular beta-catenin and LEF1 expression might help in patient risk stratification and outcome prediction, and serve as novel therapeutic targets in advanced OP-SCC.

Prognostic value of mandibular involvement in oral cavity cancers.

OBJECTIVES: The aim of the study was to determine, in a homogeneous population, the prognostic impact of mandibular involvement in oral cancers. STUDY DESIGN: Retrospective study of 117 patients with T4 squamous cell carcinoma of the oral cavity treated by surgery and radiotherapy in the ENT Department of Bichat-Claude Bernard Hospital. All patients had histologically confirmed mandibular involvement. Patients with partial involvement of the mandible underwent rim mandibulectomy (RM) and those with extensive invasion underwent segmental mandibulectomy (SM). METHODS: The local failure rate and the overall survival curves were calculated with respect to type of mandibulectomy. The causes of death were analysed. RESULTS: The surgery was conservative in 55 cases (47%) and segmental in 62 patients (53%). The degree of mandibular involvement did not influence the local failure rate (29% and 25% in the RM and SM groups, respectively). On the other hand, it strongly influenced vital outcome, as five-year survival was only 25.4% after segmental mandibulectomy, compared to 40% after rim mandibulectomy. The metastases and the second primary tumors were more frequent in the SM group. CONCLUSION: The degree of mandibular invasion influenced the survival rate of patients with squamous cell carcinoma of the oral cavity but this difference is not due to local failure.

[Diagnostic value of needle biopsy and frozen section histological examination in the surgery of primary parotid tumors]. / Valeur diagnostique de la cytoponction et de l'examen histologique extemporané dans les tumeurs parotidiennes primitives opérées.

The necessity of fine-needle aspiration biopsy (FNAB) in the diagnosis and treatment of parotid gland lesions is still controversial. We examined the accuracy of cytology and histology in a review of 128 parotid gland tumors who underwent surgery with FNAB, n = 102 and/or frozen section examination (FS), n = 94. The diagnostic sensibility and specificity for malignant or benign lesions was respectively 81.5% and 97.5% for FNAB and 75% and 100% for FS as compared with definite histology (110 tumors were benign and 18 malignant). Insufficient material for FNAB evaluation was found in 12 patients mainly with small tumors (p = 0.043) or with tumors located in the deep process of the parotid gland (p = 0.029). Surgery was inappropriate (superficial lobe resection for malignant tumor) because of 4 false negative FS diagnoses. FNAB offers valuable information in the diagnosis of nonsurgical lesions and permits to avoid FS if FNAB identify a benign lesion. FS remains mandatory if FNAB evaluation is not possible or suggests a neoplastic tumor.

[Supraglottic laryngectomy with arytenoidectomy]. / Laryngectomie supra-glottique avec aryténoïdectomie.

Relearning to swallow is frequently difficult after supraglottic laryngectomy requiring arytenoid cartilage resection. We propose a surgical procedure in which a local flap is used to close the pharyngeal defect without approximating the laryngeal remnants and the base of tongue. The procedure opens the median raphe and cuts the hyoid bone along the midline. The strap muscles, the perichondrium from the thyroid cartilage and thyroid lobe on the ispilateral side to the tumor are retracted laterally to be used to close the mucosal defect. Sixty-eight patients with T1-T3 carcinomas of the laryngeal margin with extension to an arytenoid in all cases and limited extension to the medial wall and/or anterior angle pyriform fossa in 33 underwent this surgical procedure. Only 5 patients had local recurrence and 8 a lymph node recurrence. Visceral metastases occurred in 21 patients (33%) and second primary tumors were diagnosed at the time of surgery or during follow-up in 19 patients (28%). Three and 5-year actuarial survival rates were 57 and 51%, respectively. Despite post operative radiotherapy, functional success was obtained in 50 patients (75%). This technique provided good tumor control and a high rate of satisfactory functional results in patients with tumors of lateral margin extended to one arytenoid.

[T3 and T4 cancer of the oral cavity, surgical treatment with oral tongue resection]. / Cancers T3 et T4 de la cavité buccale, traitement chirurgical par amputation de la langue mobile.

Amputation of the oral tongue is required to treat T3 and T4 bilateral tumors of the anterior two third of the tongue with or without extension to the floor of the mouth. This partial glossectomy was performed initially for 27 patients and as salvage therapy for 35 patients with recurrent diseases. The reconstruction required a flap in all cases, including 8 microvascular free flaps. Two months after surgery, two third of patients had a satisfactory swallowing hability. The functional results were worst for patients operated after radiotherapy. Actuarial survival rates were 37.5% and 22.1% at 3 and 5 years respectively. The survival rate of patients who had surgery as primary modality of treatment was significantly better as compared with those who had radiotherapy before surgery (p=0,018). This surgery offers a perfect control of tumors of the anterior floor and oral tongue and good rehabilitation provided by the conservation of the posterior tongue.

Prognostic value of lymph node involvement in oral cancers: a study of 137 cases.

OBJECTIVE: The aim of this study was to assess the prognostic value of lymph node involvement in patients with squamous cell carcinoma of the oral cavity. STUDY DESIGN: Retrospective study of 137 patients with T4 squamous cell carcinoma of the oral cavity treated by surgery and radiotherapy (84 N0, 23 N1, 16 N2,14 N3). Twenty-three patients in the N0 group had a history of surgery or radiotherapy. One hundred fourteen patients underwent limited or radical neck dissection unilaterally or bilaterally. METHODS: The histological charts were reviewed and correlated with preoperative lymph node clinical stage. The local failure rate and the overall survival curves were calculated with respect to clinical and histological stages. The causes of death were analyzed. RESULTS: No evidence of lymph node metastasis was found in 47.4% of cases (54 of 114 patients). Among the node-positive (N+) patients, 39 had rupture of the lymph node capsule (R+). In the N0 group, 27.8% of patients were N+. Regional control rates after surgery and radiotherapy were 95% at 1 year and 85.4% at 5 years. The local failure rates were 6% in N0, 8.7% in N1, 31.2% in N2, 51.7% in N3, 9% in node-negative (N-), and 29% in N+R+ patients. The overall survival rates at 3 and 5 years were, respectively, 44.7% and 34.8% in the N0 group, 37.7% and 37.7% (same rate at 3 and 5 years) in the N1 group, and 31.2% and 15.8% in the N2 group. None of the patients in the N3 group survived beyond 2 years. The overall survival rates at 5 years were 42.8% and 17.5% in the N- and N+ groups, respectively. CONCLUSIONS: In patients with locally advanced tumors (T4), clinical nodal status and histological nodal invasion were key prognostic factors. The presence of occult metastases in the N0 group justifies routine neck dissection.

[Retro-pharyngeal and pharyngeal-laryngeal lipomas]. / Lipomes rétro-pharyngés et du pharyngo-larynx.

Pharyngeal and laryngeal lipoma are uncommon mesenchymal tumors. This report discusses the clinical and pathological features of five cases and a review of the literature. Symptoms included dysphagia, throat discomfort and airway obstruction in three patients. These complaints occurred over several years. One patient had a recurrent fibrolipoma and had experienced several surgical procedures. Surgery is the treatment of choice including conservative procedures but for large tumors open surgical approaches rather than endoscopic techniques should be employed. Recurrent tumor may be a sign of incomplete excision but also of a well-differentiated liposarcoma.

[Prognostic influence of cutaneous involvement in malignant tumors of the oral cavity]. / Incidence pronostique de l'envahissement cutané dans les cancers évolués de la cavite buccale.

The aim of this study was to assess the prognostic influence of cutaneous involvement in T4 squamous cell carcinoma of the oral cavity. The population was a homogeneous group of 137 patients. Cutaneous tumor localizations were observed in 20 of them. Surgery and radiotherapy were given in 103 cases and salvage surgery was performed in 34. Local control at 5 years was achieved in 68.5 % of the patients. Carcinologic failure rate was 55 % and 27.3 % in patients with and without cutaneous involvement respectively (p =0. 013). 5-year survivor rate was also correlated with cutaneous involvement: 10 % versus 32.2 % (p <0.0001).

[Endoscopic surgical treatment of Zenker hypopharyngeal diverticuli. Apropos of 59 cases]. / Traitement par chirurgie endoscopique des diverticules hypopharyngés dits de Zenker. A propos de 59 cas.

We report our experience with 59 cases of Zenker's diverticulum, all treated endoscopically from 1979 to 1998. The ages ranged from 59 to 98 years. There were contraindications for conventional surgery or deep general anesthesia for all the patients. The surgical technique of endoscopic treatment was performed under general anesthesia, using a specially designed endoscope for exposure. Scissors, and after 1990 CO2 LASER, were used to divide the posterior cricopharyngeal muscle fibers. There was no major complication. Our results are comparable with literature, 92% success, even though a small diverticulum may paradoxically remain. Besides, from our experience, it may be necessary to perform two sessions for diverticulum larger than 3 cm. This safe and efficient treatment can be recommended for patients of all ages with a contraindication for conventional surgery.

Down-regulation of desmosomal molecules in oral and pharyngeal squamous cell carcinomas as a marker for tumour growth and distant metastasis.

Down-regulation of adhesion molecules has been observed in a number of squamous cell carcinomas (SCC) and is considered to be associated with tumour invasiveness and lymph node metastasis. The present prospective investigation aimed at analyzing the expression patterns of desmosomal markers in oral and pharyngeal SCC and correlations that may exist between these patterns and tumour behaviour. Two constitutive desmosomal molecules, desmoplakin (Dp) and plakoglobin (Pg), were examined in 26 samples of primary carcinoma of the head and neck. The correlation between Dp and Pg expression was only moderate, reflecting functional differences between the two proteins. Whereas decreased Dp and Pg expression was closely associated with distant metastasis formation, reduced Pg expression was correlated to the development of large tumours. There were also variable relationships between the expression of these markers and lymph node invasion, histological differentiation, or survival of the patients. Biochemical analysis of cytoskeletal fractions confirmed the decrease in desmosomal proteins, particularly in tumours which later developed metastases. Down-regulation of Dp and Pg in oral and pharyngeal SCC may represent a reliable marker for extensive tumour growth and the risk of distant metastasis formation, Dp and Pg apparently having metastasis- and tumour-suppressor properties, respectively.

Cytokeratin alterations as diagnostic and prognostic markers of oral and pharyngeal carcinomas. A prospective study.

Cytokeratin (CK) alterations have been reported in carcinomas from different anatomical sites, and these have been associated with specific aspects of tumour behaviour. In order to assess the relationships between CK modifications and future tumour behaviour, we conducted the present prospective study on 26 squamous cell carcinomas (SCC) of oral and pharyngeal mucosae and corresponding controls. Cytokeratins were investigated using two-dimensional gel electrophoresis and immunofluorescence techniques. All healthy tissues, oral lining and oropharyngeal mucosae, expressed the oesophageal type CKs, including CK 19. Other simple epithelial CKs (7, 8, 17 and 18) were not detected. In carcinomas originating from corresponding sites, expression of oesophageal CKs varied widely from one specimen to another, and simple epithelial keratins were often found. Statistical analysis indicated correlations between CK expression and the clinicopathological data of SCC patients. Small tumour size was strongly associated with the expression of CKs 10 and 19. Interestingly, an absence of lymph node involvement was significantly associated with CK 18 expression. Tumours giving rise to recurrences, metachronous tumours, and distant metastasis were significantly associated with an absence of CK 13. These results suggest that CKs 10, 19, 18 and 13 could be reliable diagnostic and prognostic markers in the assessment of oral and pharyngeal squamous carcinomas.

[Endoscopic treatment of a Zenker diverticulum. 50 cases]. / Traitement endoscopique des diverticules de Zenker. 50 cas.

OBJECTIVES: Endoscopy has been used for many years as an alternative to surgery for the treatment of Zenker's diverticulum. We report our experience in 50 cases. METHODS: From 1979 to 1995, we treated 50 cases of Zenker's diverticulum endoscopically. Patients' age ranged from 59 to 98 years. All patients had contraindications for conventional surgery or deep anesthesia. The surgical technique of endoscopic treatment is performed under general anesthesia using a specially designed endoscope for exposure. Scissors, then after 1990, CO2 LASER, was used to divide the posterior crico-pharyngeal muscle fibers. RESULTS: There were no major complications. Our results, 95% success, were comparable with those reported in the literature even though, paradoxically, a small diverticulum may remain. Our experience also showed that it may be necessary to perform two sessions for diverticula larger than 3 cm. CONCLUSION: This safe and efficient treatment can be recommended for patients of all ages with a contraindication for conventional surgery.

Lateral supraglottic pharyngo-laryngectomy with arytenoidectomy.

BACKGROUND: Supraglottic laryngectomy for tumors of the epilarynx requiring arytenoid cartilage resection is frequently associated with problems in relearning to swallow, and aspiration is frequent. We propose a surgical procedure in which a local flap is used to close the pharyngeal defect. METHODS: An apron skin incision is used to expose the hyoid bone and strap muscles. The median raphe is opened, and the hyoid bone is cut along the midline and released on its posterior surface. The thyrohyoid and stemothyroid muscles ipsilateral to the tumor are separated, with the perichondrium from the thyroid cartilage. This forms a continuous flap that includes the suprahyoid muscles and hemihyoid bone, together with the strap muscles and thyroid lobe that will be used for closure. RESULTS: Thirty-three patients with T1-T3 carcinomas of the laryngeal margin, with extension to one arytenoid in all cases and to the pyriform fossa in 14, underwent this procedure. Only 5/33 (15%) patients had locoregional recurrences. Visceral metastases occurred in 11/33 (33%) patients, and second primary tumors were diagnosed at the time of surgery or during follow-up in 9/33 (27%) patients. Three-year and 5-year actuarial survival rates were 57% and 51%, respectively. Despite the need for radiotherapy in 26 patients, functional success was obtained in 26/33 cases (79%). CONCLUSION: This technique provided good tumor control and a high rate of satisfactory functional results. It can be applied to patients with tumors of the lateral margin which unilaterally extend to the aryepiglottic fold, the arytenoid, and the medial well of the pyriform fossa.

[Total glossectomy with laryngectomy]. / Glossectomie totale avec laryngectomie.

Because local control of locally advanced cancer of base of tongue and larynx managed with combined chemotherapy and radiotherapy is poor, we proposed total glossectomy with total laryngectomy. Twenty-one patients underwent this operation over a period of 8 years. It was a salvage surgery for 15 patients, and an up-front surgery for the 6 others. Postoperative complications occurred in ten patients, and three patients died in the postoperative period. Mean total duration of hospitalisation was 40 days. Oral feeding could be achieved in 14 patients (mean delay: 46 days), but satisfactory oesophageal voice has never been obtained. We can conclude from the analysis of this series that total glossectomy with total laryngectomy is a heavy surgery, which leads to frequent complications, severe functional sequellae, and poor survival. However, control of pain can be obtained, that justifying this heavy procedure. We recommend that patients and relatives should be fully informed about the consequences of surgery before final decision.

Laryngectomized patients' education and follow-up.

Functional and aesthetic problems due to mutilating surgical excisions and adjuvant radiotherapy prolonging the therapeutic period and increasing consequences, are common to all cervicofacial tumors. Laryngectomy is the most representative example, because it affects the aero-digestive tract, the site of major functions; breathing, phonation and swallowing. It necessitates excellent information to the patient post-operatively, and then adapted rehabilitation requiring the learning of oesophageal speech. A close follow-up is required to track loco-regional relapses, secondary neoplastic sites and metastases, cessation of alcohol and tobacco use, and to provide family, social and professional rehabilitation. There are often problems to manage with socio-culturally disadvantaged classes, and physically and psychologically fragile patients, whose hope of surviving is, in general, mediocre.

[Malignant tumors of the petrous bone. Apropos of 25 cases]. / Tumeurs malignes du rocher. A propos de 25 cas.

Twenty five cases of malignant tumors of the petrous bone are presented. Prognosis depends on the histology and on the local invasion which dictate the possibility of curative surgery. Squamous cell carcinoma of the middle ear and other invasive tumors have a bad prognosis, and in spite of the progress of modern image technology, the peripetrous extension of the tumors are often underestimated. Actuarial two years survival for squamous cell carcinoma was 38%. Total excision needs at least a subtotal petrous resection with, in some cases meningal and internal carotid resection. In all cases, surgery was followed by radiation. Low grade malignant tumors had a better prognosis and required a more limited resection. In these cases, when necessary, facial nerve can be repaired by a cable graft at the time of initial surgery.

[Lymphoepithelial hyperplasia of the parotid gland and HIV infection]. / Hyperplasie lymphoépithéliale de la parotide et infection par le VIH.

A retrospective review of 10 patients with parotid enlargement is presented. Nine patients were known to be antibody positive for the HIV and one was subsequently tested to be positive. Parotid enlargement was nodular in 9 patients, bilateral in 7, unilateral in 2. One patient had a diffuse enlargement with xerostomia and xerophtalmy. Histological results confirmed begnin lymphoepithelial lesion in all patients. Pathogenesis, diagnostic, pronostic and therapeutic problems are discussed in a literature review.

[Cancer of the tongue in women. A propos of 40 cases]. / Cancer de langue chez la femme. A propos de 40 cas.

Forty women, average age of 54, have been treated in first intention or after the failure of a previous treatment, for a squamous cell carcinoma of the tongue. Eighteen (45%) had no risk factors and 9 were under forty years of age. The oral tongue was the most frequent localisation in the group of patient without risk factors. Nineteen local failures were observed. Actuarial three-years survival was 36%. We believe that the poor prognosis of female tongue squamous carcinoma requires aggressive treatment with combined surgery and brachytherapy on the primary lesion and prophylactic neck dissection even in patients without palpable cervical nodes.