P223 Bisphosphonates jaw osteonecrosis: conservative versus non conservative management of a group of 47 patients

198 P221 Khat inhibits proliferation of normal oral keratinocytes in monolayers and organotypic cultures O. Lukandu1 , E. Dimba1 , O. Vintermyr1 , D. Costea1 *, A. Johannessen1 . 1 University of Bergen, Norway, 2 University of Nairobi, Kenya Background: Khat chewing is widely practised in Eastern Africa and the Middle East. Previous studies have suggested an association between khat use and oral lesions including hyperkeratosis and cancer. Objective: This study sought to compare the effects of an organic extract of khat on proliferation of normal human oral keratinocytes in monolayers and in organotypic co-cultures (with normal human oral fibroblasts). Materials: The organic extract was acquired from fresh khat grown in Kenya and normal oral cells were isolated from the buccal mucosa of consenting healthy volunteers undergoing surgical removal of wisdom teeth. Results: In monolayers, cell proliferation was inhibited by khat concentrations below 32 mg/ml. The khat concentration resulting in 50% inhibition of growth (IC50 ) after 6 days in culture was estimated to be 15 mg/ml. After 72hrs of exposure, khat treated cells accumulated within the G1 phase whereas the proportion of cells in the S-phase and G2/M phase decreased, suggesting that the growth inhibition was due to a specific cell cycle arrest at the G1 phase. In organotypic models, khat induced a concentration dependent decrease in epithelial thickness. Total epithelial thickness dropped from 407±52 mm in the controls to 162±11 mm (p = 0.053) and 113±13mm (p = 0.023) when treated with 100 mg/ml and 316 mg/ml respectively. Treatment with khat led to a marked decrease in the proportion of basal and spinous cell layers and an increase in the proportion of superficial cell layer when compared to the total thickness. Conclusion: Since the khat concentrations used in this study are comparable to those found in vivo during khat chewing, the results in this study point to reduced keratinocyte proliferation due to premature differentiation as a possible mechanism that could be operative in the oral mucosa of khat chewers. Keywords: khat, keratinocytes, proliferation, organotypic P222 Higher pretreatment platelet count correlates with unfavorable prognosis in nasopharyngeal carcinoma H.W. Chen1 *, Y.C. Chang3 , Y.J. Chen2 , Y.F. Chang2 , C.J. Liu2 , J.J. Hwang1 . 1 National Yang-Ming University, Taiwan, 2 Mackay Memorial Hospital, Taiwan, 3 Tamkang University, Taiwan Introduction: Thrombocytosis has been reported to be associated with a poor prognosis in some cancers. However, the prognostic value of the platelet count in patients with nasopharyngeal carcinoma is unclear. Methods: Medical records of patients with nasopharyngeal carcinoma (NPC) diagnosed between January 2002 and October 2005 and who were treated with concurrent chemoradiation therapy (CCRT) and followed at Mackay Memorial Hospital were retrospectively reviewed. A total of 83 patients fulfilled the criteria. CCRT was administered as follows: radiotherapy (RT) of greater than 70 Gy to the primary tumor bed and gross adenopathy was accompanied by monthly chemotherapy (CT) during RT and for two cycles after RT. CT included cisplatin at 12 (regimen I, 57 patients) or 15 (regimen II, 26 patients) mg/m2 /d plus flurouracil at 600 (regimen I) or 750 (regimen II) mg/m2 /d for 5 days. The pre-CCRT platelets were compared in various subgroups with an unpaired t test. Overall survival (OS) and disease-free survival (DFS) were examined by multivariate modeling, assessing the prognostic value of pre-CCRT platelet count, sex, age, tumor stage, and treatment regimen. Results: Cox’s proportional hazards model indicated a higher pretreatment platelet count independently predicted poorer

Poster abstracts, Saturday 19 May OS (RR 1.009, 95% CI 1.001 1.016, p = 0.018) and DFS (RR 1.009, 95% CI 1.002 1.016, p = 0.010). Women had better OS and DFS than men (RR 0.243, 95% CI 0.068 0.876, p = 0.031; RR 0.024, 95% CI 0.102 0.851, p = 0.024; respectively). The preCCRT platelet count, however, was not significantly correlated with any clinical factors. Discussion: These data suggest that an elevated pre-CCRT platelet count may be an unfavorable prognostic indicator in NPC. Keywords: platelet count, nasopharyngeal carcinoma, prognosis P223 Bisphosphonates jaw osteonecrosis: conservative versus non conservative management of a group of 47 patients C. Madrid1 *, M. Broome2 , K. Bouferrache1 , B. Jaques2 . Lausanne University Medical Outpatient Hospital, Switzerland, 2 Lausanne University Hospital, Switzerland 1

Osteonecrosis of the jaw (ONJ) is associated with the use of bisphosphonates (mainly pamidronate and zoledronic acid). The aim of this study was to assess on clinical grounds the different modalities of management of ONJ. 47 ONJ patients, 30 women and 17 men, under or after bisphosphonates treatment, have been followed from July 2004 until today. Mean age at the onset of ONJ was 67 (47 83). The indications where splitted up into 23 multiple myelomas, 17 breast cancers and 7 prostate cancers. Mean life expectancy was 16 months (6 to 26). The bisphosphonate was zoledronic acid in 37 cases (24 alone, 13 after pamidronate), pamidronate alone in 5 cases, ibandronate in 2 cases. The mean number of therapy cycles at the onset of ON was 32 cycles (18 48) for zoledronic acid, 39 cycles (19 58) for zoledronic acid+ pamidronate. The follow up duration was 1 to 28 months, mean 12 months. The site of ONJ was splitted as follows: mandible: 19, both jaws: 14, maxilla: 14. The patient had a single bone exposition in 22 cases and multiple bone expositions in 25 cases. Patient had a history of dental procedures in 37 cases. Diffuse pain affecting a dentate area of the alveolar crest was the first sign before extraction in 29 cases. An aggressive management (debridement and bone stimulation, flap coverage, interruptive resection and reconstruction) was performed in 14 cases. Conservative management (antibiotics, home daily instillations of chlorhexidine, on demand sequestrectomy) was performed in 33 patients. Aggressive management showed poorer results (recurrences: 20, plate exposition: 1, spontaneous fracture: 2) and higher VAS pain assessment (6) than conservative management (18 stable results, VAS:4), 13 slow evolutions to spontaneous elimination of sequesters (VAS: 4) 2 second localization of ONJ. Keywords: Osteonecrosis, Bisphosphonates, Jaw, Management P224 Expression of claudins 1, 4, 5, 7 and occludin and the relationship with prognosis in squamous cell carcinoma of the tongue O.B. Ibrahim1 *, V. Suvi-Tuuli3 , N. Ahti4 , S. Ylermi5 , S. Tuula1 . Finland and Oulu University Hospital, Finland, 2 University College Hospital, Nigeria, 3 University of Helsinki, Finland, 4 University of Oulu, Finland, 5 University of Oulu and Oulu University Hospital, Finland 1

Introduction: Claudins and occludin are tight junctional proteins known to play a role in normal tissues and cancers. We analyzed the distribution patterns of claudins 1, 4, 5, 7 and occludin in superficial and deep parts of squamous cell carcinoma (SCC) of the tongue and their relationship to overall patient survival. Methods: SCCs of 97 patients were studied by immunohistochemistry for claudins 1, 4, 5, 7 and occludin. Immunoreactivity was scored for intensity and quantity in the superficial and deep