• Nutrition and pharyngeal cancer: results from a case-control study in Spain.

• Do Ki67, S-phase, S + G2M and DNA ploidy, evaluated by flow cytometry, reveal locoregional metastasis in oral cavity and oropharynx carcinomas?

• Correlation of p21 gene codon 31 polymorphism and TNF-alpha gene polymorphism with nasopharyngeal carcinoma.

• Combined modality treatment of oral and oropharyngeal cancer including neoadjuvant intraarterial cisplatin and radical surgery followed by

• Importance-rating using the University of Washington quality of life questionnaire in patients treated by primary surgery for oral and

• Cell cycle-dependent expression of volume-activated chloride currents in nasopharyngeal carcinoma cells.

• Fluorescence spectral imaging for characterization of tissue based on multivariate statistical analysis.

• Issues in optimization for planning of intensity-modulated radiation therapy.

• Craniofacial resection of advanced juvenile nasopharyngeal angiofibroma.

• Peptide transporter (TAP-1 and TAP-2)-independent endogenous processing of Epstein-Barr virus (EBV) latent membrane protein 2A: implications for

• Differential expression and topography of adhesion molecules in laryngeal and oropharyngeal carcinomas.

• The evaluation of dysphagia following radical surgery for oral and pharyngeal carcinomas by cine-magnetic resonance imaging (Cine-MRI).

• [Occupational exposure and cancer of the oral cavity and pharynx]

• Distant metastases from nasopharyngeal carcinoma at Kenyatta National Hospital, Nairobi.

• Evidence of increased Id-1 expression and its role in cell proliferation in nasopharyngeal carcinoma cells.

• Neoglottic formation from posterior pharyngeal wall conserved in surgery for hypopharyngeal cancer.

• Abnormalities of molecular regulators of proliferation and apoptosis in carcinoma of the oral cavity and oropharynx.

• Significance of epidermal growth factor receptor and tumor associated tissue eosinophilia in the prognosis of patients with nasopharyngeal

• [Tonsillar carcinoma--clinical assessment and analysis of treatment results]

• Sentinel lymph node analysis in squamous carcinoma of the oral cavity and oropharynx.

• [Surgical methods of removal of T4 nasopharyngeal malignancies. A preliminary report on 18 cases]

• [Invasive vascular tumor of the oropharynx]

• Nasopharyngectomy for recurrent nasopharyngeal carcinoma: a review of 31 patients and prognostic factors.

• High-dose, high-precision treatment options for boosting cancer of the nasopharynx.

• Weight loss predicts mortality after recurrent oral cavity and oropharyngeal carcinomas.

• [Electrochemotherapy, a new antitumor treatment: first clinical trial]

• [Significance of her2 oncogene expression in primary nasopharyngeal carcinoma]

• [Surgical treatment of neck lymph nodes in squamous cell carcinoma of the pyriform sinus]

1
UI - 12211047
AU - Uzcudun AE; Retolaza IR; Fernandez PB; Sanchez Hernandez JJ; Grande AG;
TI - Garcia AG; Olivar LM; De Diego Sastre I; Baron MG; Bouzas JG Nutrition and pharyngeal cancer: results from a case-control study in Spain.
SO - Head Neck 2002 Sep;24(9):830-40
AD - Servicio de Oncologia Radioterapica, Hospital Universitario La Paz, Paseo de la Castellana, 261, 28046, Madrid, Spain.
BACKGROUND: Oropharyngeal and hypopharyngeal cancer is increasing all over the world, frequently affecting more and more women and younger individuals and not only the typical 50- to 60-year-old heavy smoker and drinking man. In addition, 5-year overall survival rate remains poor (30% to 40% in most series), despite advances in treatment. Therefore, it is crucial to understand as accurately as possible the risk factors for these malignancies to improve primary prevention. METHODS: We report the results from a case-control study of pharyngeal cancer risk factors conducted in Spain involving 232 consecutive patients who were gender- and age-matched with 232 controls. Data were collected by interviewer-administered personal interview. RESULTS: Our results show that low intake of fruit, fruit juice, uncooked vegetables, dietary fiber-containing foods (legume and cereals), fish, milk, and dairy products is an independent risk factor for pharyngeal cancer and that high consumption of meat and fried foods also increases the risk once data are adjusted for tobacco smoking and alcohol drinking. CONCLUSIONS: Although findings for fruit, juice, and uncooked vegetables are in accordance with those from other authors and can be explained on a biologic basis, the relationship between pharyngeal cancer and dietary excess of saturated fatty acids needs experimental investigation. Findings for milk, dairy products, and fish also warrant more detailed epidemiologic research because of conflicting data reported in the literature and because of the reportedly ambiguous role of retinol in human cancers. No conclusive explanations for the protective effect of dietary fiber-containing foods can be put forward today. Our results are uniquely attributable to oropharyngeal and hypopharyngeal cancers because of the small size of our nasopharyngeal cancer subsample. Copyright 2002 Wiley Periodicals, Inc. Head Neck 24: 830-840, 2002

2
UI - 11956630
AU - Tirelli G; Sidari L; Giacomarra V; Papanikolla L; Sasso F; Russolo M;
TI - Melato M Do Ki67, S-phase, S + G2M and DNA ploidy, evaluated by flow cytometry, reveal locoregional metastasis in oral cavity and oropharynx carcinomas?
SO - Oncol Rep 2002 May-Jun;9(3):575-80
AD - Department of Otorhinolaryngology, Cattinara Hospital, I-34149 Trieste, Italy.
Tumour cell proliferation is an important biological prognostic parameter to be considered alongside clinical and histopathological parameters. It has been evaluated by immunohistochemistry using proliferative markers (PCNA, Ki67, etc.) and by flow cytometry considering DNA content, growth fraction (S + G2M) and S-phase fraction. Our aim was to evaluate by flow cytometry both Ki67 and S-phase fraction, S + G2M, DNA content in patients surgically treated for oral cavity and/or oropharynx carcinomas. The study, performed on archival material, analysed the significance and prognostic reliability of these biological parameters to reveal locoregional metastasis and evaluated their possible correlation with clinical and histopathological parameters. In conclusion, tumour cell proliferation seems not to be useful in revealing the presence of locoregional metastasis in oral cavity and oropharynx carcinomas. Thus, new approaches are required.

3
UI - 11968052
AU - Tsai MH; Chen WC; Tsai FJ
TI - Correlation of p21 gene codon 31 polymorphism and TNF-alpha gene polymorphism with nasopharyngeal carcinoma.
SO - J Clin Lab Anal 2002;16(3):146-50
AD - Department of Otolaryngology, China Medical College Hospital, Taichung, Taiwan.
Background p21 (WAF1/CIP1) is a downstream protein from p53 and can arrest the cell cycle at the G1/S phase in response to signal from p53. The most frequently seen polymorphic site is at codon 31, where a base change from AGC to AGA causes an amino acid change from serine to arginine. Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that is secreted from macrophages, and is related to a sequence of events in the response to inflammation and cancer formation. The TNF-alpha gene promoter -308 G/A polymorphism has been reported to be associated with some cancers. In this study, these polymorphisms were proposed to be a candidate genetic marker of nasopharyngeal carcinoma (NPC). The distribution was analyzed in 47 NPC patients and a control group of 119 healthy people. The association of the p21 codon 31 polymorphism with NPC was detected by polymerase chain reaction (PCR) and restriction analysis by Blp I endonuclease, and calculated by the chi-square test. The TNF-alpha gene promoter -308 G/A polymorphism was identified by Nco I endonuclease. The distribution of the gene p21 codon 31 polymorphisms showed no significant difference between the two groups. The serine form of p21 codon 31 was more prominent in smokers than nonsmokers among the NPC patients (P < 0.05). There was no significant difference in the distribution of TNF-alpha gene promoter -308 G/A polymorphism between control and cancer patients. The results indicate that the gene p21 codon 31 polymorphism and TNF-alpha promoter -308 polymorphism are not correlated with NPC. However, the difference between smokers and nonsmokers suggests that an environmental factor may be involved in association with the p21 gene in the formation of NPC. Copyright 2002 Wiley-Liss, Inc.

4
UI - 12069515
AU - Kovacs AF; Schiemann M; Turowski B
TI - Combined modality treatment of oral and oropharyngeal cancer including neoadjuvant intraarterial cisplatin and radical surgery followed by concurrent radiation and chemotherapy with weekly docetaxel - three year results of a pilot study.
SO - J Craniomaxillofac Surg 2002 Apr;30(2):112-20
AD - Department of Maxillofacial Plastic Surgery, Johann Wolfgang Goethe-University Frankfurt Medical School, Frankfurt am Main, Germany. A.Kovacs@em.uni-frankfurt.de
BACKGROUND: A new four-modality treatment of primary oral and oropharyngeal squamous cell carcinomas was evaluated with regard to feasibility, tolerance, and survival. PATIENTS AND METHODS: Seventy three operable patients (100%) with histologically proven untreated stage I to stage IV disease received at least one cycle of neoadjuvant intraarterial chemotherapy with 150 mg/m(2) cisplatin neutralized with sodium thiosulphate, followed by radical operation for the tumour with a simultaneous selective neck dissection (clinically negative neck), or modified radical neck dissection (nodal involvement), followed by adjuvant chemoradiation over 5 weeks (51.9 Gy, systemic docetaxel 25 mg/m(2), once every week). RESULTS: Ninety-six per cent of patients were operated on, 68% had postoperative radiation, 57% concomitant chemotherapy; 44% fulfilled the complete protocol. There have been 11 local or regional recurrences to date, three of which were treated by salvage surgery. Eighteen patients died, in nine of them death was tumour-related. Seventy five per cent lived after a median observation time of 33 months. Cumulative survival was 74% calculated for 4 years. CONCLUSION: The presented multimodality regimen proved feasible and showed better survival for the whole population and for all tumour stages when compared with the treatment-dependent prognosis index of the DOSAK (German-Austrian-Swiss Cooperative Group on tumours of the maxillofacial region). Copyright 2002 Published by Elsevier Science Ltd. on behalf of European Association for Cranio-Maxillofacial Surgery.

5
UI - 12069517
AU - Rogers SN; Laher SH; Overend L; Lowe D
TI - Importance-rating using the University of Washington quality of life questionnaire in patients treated by primary surgery for oral and oro-pharyngeal cancer.
SO - J Craniomaxillofac Surg 2002 Apr;30(2):125-32
AD - Mossley, Cheshire, UK. snrogers@globalnet.co.uk
BACKGROUND: There are now several validated and widely accepted head and neck cancer questionnaires. These record patients subjective levels of function and dysfunction, as well as symptoms related to their cancer and its treatment. One popular measure is the University of Washington head and neck cancer questionnaire (UW-QOL). Domain importance-ratings were added to the second version of the questionnaire, which was published in 1997. It is unique amongst head and neck cancer questionnaires in this respect. AIM: The purpose of the study was to evaluate UW-QOL with particular reference to domain importance-rating. It was also the intention to investigate how the importance-ratings related to 'quality of life' and comment on the cumulative scoring of the questionnaire. METHODS: Forty-eight patients with previously untreated oral or oro-pharyngeal cancer were recruited. All were treated by primary surgery. Questionnaires were completed pre-operatively, 6 months and 1 year post-operatively. RESULTS: This study demonstrates a wide variation in importance-ratings. Both pre- and post-treatment there was a general lack of correlation between importance-rating and domain scores. At all time points, patients tended to rate speech, chewing and swallowing as more important than the other UW-QOL domains. The cumulative UW-QOL score correlated strongly with the new single item QOL question. CONCLUSION: It remains unclear how best to incorporate importance-ratings into a single UW-QOL total score. However, for individual patients they can assist in setting priorities in treatment strategies. Copyright 2002 European Associaton for Cranio-Maxillofacial Surgery. Published by Elsevier Science Ltd. All rights reserved.

6
UI - 12225994
AU - Chen L; Wang L; Zhu L; Nie S; Zhang J; Zhong P; Cai B; Luo H; Jacob TJ
TI - Cell cycle-dependent expression of volume-activated chloride currents in nasopharyngeal carcinoma cells.
SO - Am J Physiol Cell Physiol 2002 Oct;283(4):C1313-23
AD - School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3US, Wales, UK.
Patch-clamping and cell image analysis techniques were used to study the expression of the volume-activated Cl(-) current, I(Cl(vol)), and regulatory volume decrease (RVD) capacity in the cell cycle in nasopharyngeal carcinoma cells (CNE-2Z). Hypotonic challenge caused CNE-2Z cells to swell and activated a Cl(-) current with a linear conductance, negligible time-dependent inactivation, and a reversal potential close to the Cl(-) equilibrium potential. The sequence of anion permeability was I(-) > Br(-) > Cl(-) > gluconate. The Cl(-) channel blockers tamoxifen, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), and ATP inhibited I(Cl(vol)). Synchronous cultures of cells were obtained by the mitotic shake-off technique and by a double chemical-block (thymidine and hydroxyurea) technique. The expression of I(Cl(vol)) was cell cycle dependent, being high in G(1) phase, downregulated in S phase, but increasing again in M phase. Hypotonic solution activated RVD, which was cell cycle dependent and inhibited by the Cl(-) channel blockers NPPB, tamoxifen, and ATP. The expression of I(Cl(vol)) was closely correlated with the RVD capacity in the cell cycle, suggesting a functional relationship. Inhibition of I(Cl(vol)) by NPPB (100 microM) arrested cells in G(0)/G(1). The data also suggest that expression of I(Cl(vol)) and RVD capacity are actively modulated during the cell cycle. The volume-activated Cl(-) current associated with RVD may therefore play an important role during the cell cycle progress.

7
UI - 12216876
AU - Qu JY; Chang H; Xiong S
TI - Fluorescence spectral imaging for characterization of tissue based on multivariate statistical analysis.
SO - J Opt Soc Am A Opt Image Sci Vis 2002 Sep;19(9):1823-31
AD - Department of Electrical and Electronic Engineering, Hong Kong University of Science and Technology, Kowloon, China. eequ@ust.hk
A novel spectral imaging method for the classification of light-induced autofluorescence spectra based on principal component analysis (PCA), a multivariate statistical analysis technique commonly used for studying the statistical characteristics of spectral data, is proposed and investigated. A set of optical spectral filters related to the diagnostically relevant principal components is proposed to process autofluorescence signals optically and generate principal component score images of the examined tissue simultaneously. A diagnostic image is then formed on the basis of an algorithm that relates the principal component scores to tissue pathology. With autofluorescence spectral data collected from nasopharyngeal tissue in vivo, a set of principal component filters was designed to process the autofluorescence signal, and the PCA-based diagnostic algorithms were developed to classify the spectral signal. Simulation results demonstrate that the proposed spectral imaging system can differentiate carcinoma lesions from normal tissue with a sensitivity of 95% and specificity of 93%. The optimal design of principal filters and the optimal selection of PCA-based algorithms were investigated to improve the diagnostic accuracy. The robustness of the spectral imaging method against noise in the autofluorescence signal was studied as well.

8
UI - 12118386
AU - Verhey LJ
TI - Issues in optimization for planning of intensity-modulated radiation therapy.
SO - Semin Radiat Oncol 2002 Jul;12(3):210-8
AD - Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA.
The clinical use of intensity-modulated radiation therapy (IMRT) is expanding rapidly in academic and, more recently, in community-based radiotherapy centers due to a high level of clinician interest, improving reimbursement patterns, and the availability of the tools required to plan and deliver IMRT plans. These tools include inverse planning optimization algorithms and linear accelerator control systems with automated, multifield delivery capabilities. The hazards of this new technology are due primarily to the nonintuitive nature of the inverse planning process and the highly complex methods of delivery required for IMRT dose delivery. Important efforts are being made to define the required quality assurance for these computer-optimized IMRT plans and to find ways to reduce their complexity without reducing the quality of the resulting plans. By minimizing the complexity of these dose plans, one also minimizes the treatment time and the probability of dose delivery errors. Methods of optimization and evaluation of dose plans and practical considerations in inverse planning are discussed. In addition, this article points out the potential hazards of inverse-planned IMRT and discusses methods by which the complexity of these plans might be reduced. Copyright 2002, Elsevier Science (USA). All rights reserved.

9
UI - 12220215
AU - Bales C; Kotapka M; Loevner LA; Al-Rawi M; Weinstein G; Hurst R; Weber
TI - RS Craniofacial resection of advanced juvenile nasopharyngeal angiofibroma.
SO - Arch Otolaryngol Head Neck Surg 2002 Sep;128(9):1071-8
AD - University of Pennsylvania Medical School, Philadelphia, USA.
OBJECTIVE: To describe the results of a craniofacial approach to resection of stage IIIB juvenile nasopharyngeal angiofibroma, performed by an integrated skull base surgical team. DESIGN: A retrospective case-series review was conducted with postoperative follow-up ranging from 28 to 63 months. SETTING: Operations were performed at a tertiary medical center. PATIENTS: A referred sample of 5 male patients, ranging in age from 10 to 23 years (mean, 15 years). INTERVENTIONS: All patients underwent resection of nasopharyngeal angiofibromas with intracranial extension. The procedure involved an infratemporal fossa approach via zygomatic osteotomy and subtemporal craniectomy. Anterior exposure was gained through a standard facial translocation. Dissection of the cavernous carotid artery was required in 3 patients. MAIN OUTCOME MEASURES: Intraoperative and postoperative morbidity. RESULTS: The average operating time was 12 hours 47 minutes. Estimated blood loss ranged from 700 to 1750 mL (mean, 1120 mL), with 2 patients requiring intraoperative transfusion. Patients were hospitalized for a mean duration of 5.6 days. Long-term morbidity includes facial dysesthesia, nasal crusting, and malodorous nasal discharge. No patients sustained stroke, oculomotor dysfunction, vision loss, or auditory impairment. At most recent follow-up, which ranges from 28 to 63 months, tumor recurrence has been confirmed in 1 patient. CONCLUSIONS: A combined craniofacial approach is appropriate for juvenile nasopharyngeal angiofibroma that extends intracranially. Complete tumor removal with acceptable morbidity can be expected.

10
UI - 8764046
AU - Khanna R; Burrows SR; Moss DJ; Silins SL
TI - Peptide transporter (TAP-1 and TAP-2)-independent endogenous processing of Epstein-Barr virus (EBV) latent membrane protein 2A: implications for cytotoxic T-lymphocyte control of EBV-associated malignancies.
SO - J Virol 1996 Aug;70(8):5357-62
AD - Queensland Institute of Medical Research, The Bancroft Centre, Brisbane, Australia.
Major histocompatibility [correction of histocampatability] complex (MHC) class I-restricted cytotoxic T lymphocytes (CTLs) recognizing Epstein-Barr virus (EBV) latent antigens play a pivotal role in restricting the proliferation of EBV-infected normal B cells. However, it is now well established that most of the EBV-associated malignancies escape this potent CTL response in vivo. This resistance to immune surveillance is not due to an obvious CTL dysfunction but has been partly attributed to the down-regulation of the peptide transporters, TAP-1 and TAP-2, thus restricting the endogenous loading of MHC class I molecules with peptides derived from viral nuclear antigens. In the present study we have explored the possibility that EBV latent membrane protein 2A (LMP2A), which is often expressed in many of the EBV-associated malignancies, such as nasopharyngeal carcinoma and Hodgkin's disease tumors, can be endogenously processed through an alternative, TAP-1- and TAP-2-independent pathway. The data presented in this study clearly demonstrate not only that LMP2A can be processed by a TAP-independent mechanism but also that tumor cells with down-regulated TAP expression can be efficiently recognized by LMP2A-specific T cells following infection with recombinant vaccinia virus encoding this protein. We propose that since LMP2A is a membrane protein, it is directly translocated into the secretory pathway and the processing enzymes present in the endoplasmic reticulum are capable of generating the relevant peptide epitopes for MHC binding. The present finding of TAP-1- and TAP-2-independent presentation of LMP2A epitopes suggests a novel mechanism for immune targeting of EBV-positive malignancies, such as nasopharyngeal carcinoma and Hodgkin's disease tumors.

11
UI - 11936920
AU - Ricci E; Cavalot AL; Sanvito F; Bussi M; Albera R; Staffieri A;
TI - Cortesina G; Marchisio PC Differential expression and topography of adhesion molecules in laryngeal and oropharyngeal carcinomas.
SO - Acta Otolaryngol 2002 Mar;122(2):234-40
AD - Ear, Nose and Throat Clinic II, University of Turin, Italy. eu.ricci@tiscalinet.it
This work describes the different patterns of expression of integrins and extracellular matrix proteins in normal and transformed mucosa in laryngeal and oropharyngeal carcinomas. Samples from each tumor group were sectioned and examined by immunohistochemistry using monoclonal antibodies raised against integrin chains (alpha2, alpha3, alpha6, beta1 and beta4) and their ligands (laminins 1 and 5, collagen type IV and two fibronectin isoforms: ED-A and ED-B). Controls were provided by samples of tumor-free laryngeal and oropharyngeal mucosa that had been removed during the surgical procedure. We found that the known distinct topographical pattern of integrins and the continuity of basement membrane components was altered in both groups but that the extent of changes was significantly more marked in oropharyngeal tumors, which are known to be more infiltrating and diffusive and to have a bad prognosis. These molecular patterns of expression can be used as an additional prognostic factor as they suggest a greater biological tumor aggressiveness of oropharyngeal tumors. We suggest that performing immunohistochemical analysis on biopsy samples may help in selecting the correct therapeutic strategy for these tumors and enable more accurate follow-up. The above-mentioned molecules may become part of the diagnostic toolbox of head and neck surgical pathologists.

12
UI - 12140643
AU - Kitano H; Asada Y; Hayashi K; Inoue H; Kitajima K
TI - The evaluation of dysphagia following radical surgery for oral and pharyngeal carcinomas by cine-magnetic resonance imaging (Cine-MRI).
SO - Dysphagia 2002 Summer;17(3):187-91
AD - Department of Otolaryngology, Head and Neck Surgery, Shiga University of Medical Science, Otsu, Japan. hkitano@belle.shiga-med.ac.jp
Cine-magnetic resonance imaging (cine-MRI) creates moving pictures by a video system and turbo-flash method that allow for high-speed MRI. This report describes our experience using this new technique for dynamic imaging using the fast spoiled GRASS (SPGR) sequence to study swallowing in patients with dysphagia following radical surgery for oral cancer. We defined two new parameters, laryngeal elevation and the angle of the epiglottis, to quantify swallowing ability by cine-MRI. These variables were markedly different in patients with dysphagia than they were in healthy controls. Cine-MRI not only provides dynamic images of swallowing but can generate objective measures of swallowing ability as well.

13
UI - 12189574
AU - Riechelmann H
TI - [Occupational exposure and cancer of the oral cavity and pharynx]
SO - Laryngorhinootologie 2002 Aug;81(8):573-9
AD - Univ. HNO-Klinik Ulm, Germany. herbert.riechelmann@medizin.uni-ulm.de
BACKGROUND: Occupational risk factors for the development of laryngeal cancer are well accepted, whereas the etiologic relationship between occupational exposure to various noxious influences and the development of cancer of the oral cavity and pharynx remain a matter of debate. Based on published data, occupational risk factors for cancer of the oral cavity and pharynx should be evaluated. METHODS: Publications since 1990 listed in the National Library of Medicine, textbooks and data obtained from the German Employer's Liability Insurance Association were evaluated. RESULTS: In several tobacco- and alcohol-adjusted case-control and cohort studies, an association with occupation in construction and metalworking industries, as painters, carpenters and machine operators was consistently found. The relative risks or standardized mortality rates ranged between 1.5 and 3. Some recent investigations found an association for workers in the paper and rubber industry. The results in regard to the textile and woodworking industry were inconclusive. CONCLUSION: In cases with moderate isolated tobacco or moderate isolated alcohol consumption, the risk attributable to occupational factors and smoking or drinking are of similar magnitude. According to German jurisdiction, a partial compensation of the acquired disability is then justified. In pronounced combined tobacco and alcohol consumption, the non-occupational risk factors increase exponentially and occupational risks attain marginal weight.

14
UI - 12199453
AU - Gacani W; Bal IS; Babu MA; Oburra HO
TI - Distant metastases from nasopharyngeal carcinoma at Kenyatta National Hospital, Nairobi.
SO - East Afr Med J 2001 Dec;78(12):678-81
AD - ENT-HN Surgical Unit, Forces Memorial Hospital, Nairobi.
OBJECTIVES: To determine the frequency and site of distant infraclavicular metastases of nasopharyngeal carcinoma (NPC), the stage of the primary tumour at presentation of metastasis and the histological trends. To determine if there is a correlation between the follow-up rate and different metastatic sites. DESIGN: A retrospective study. SETTING: Ear nose and throat surgical and radiotherapy clinics at Kenyatta National Hospital, Nairobi. SUBJECTS: Case notes, radiotherapeutic and laboratory records of patients presenting with NPC distant NPC metastases was 14.6% and 92.3% manifested within 24 months of admission. It was most frequent in the males, a younger age group and early T1 disease. Bilaterality of the neck nodes had no relevance on metastatic rate. The bone (66.7%) was the most common distant metastatic destination followed by the liver (23.2%). Liver metastasis was associated with a shorter follow-up period. CONCLUSION: Apart from the late presentation of locoregional disease, the findings are similar to studies elsewhere. The preponderance of early primary disease in patients with distant metastasis need further appraisal as it preliminarily suggests existence of specific biological markers that favour metastases. This can only be done after recruiting more cases.

15
UI - 12203366
AU - Wang X; Xu K; Ling MT; Wong YC; Feng HC; Nicholls J; Tsao SW
TI - Evidence of increased Id-1 expression and its role in cell proliferation in nasopharyngeal carcinoma cells.
SO - Mol Carcinog 2002 Sep;35(1):42-9
AD - Department of Anatomy, Faculty of Medicine, University of Hong Kong, Hong Kong, SAR, China.
Inhibitor of differentiation or DNA binding (Id-1), a helix-loop-helix transcription factor, has recently been shown to inactivate the retinoblastoma (RB)/p16(INK4a) pathway through down-regulation of p16(INK4a) and increasing phosphorylation of RB in certain cell types. Nasopharyngeal carcinoma (NPC) is a common cancer in Hong Kong, and inactivation of the tumor suppressor RB at transcription level is a rare event in NPC. The objective of this study was to investigate the role of Id-1 in NPC cell proliferation and its expression in NPC samples. An NPC cell line, CNE1, was transfected with a retroviral vector containing a full-length Id-1 cDNA, and six stable transfectant clones were isolated with differential Id-1 expression levels. The effect of ectopic Id-1 expression on serum-independent cell growth, cell-cycle distribution, and expression of proteins associated with RB pathway was studied. The Id-1 expression in five NPC samples was also investigated using immunohistochemistry. Ectopic Id-1 expression in CNE1 cells resulted in an increase in serum-independent cell growth, percentage of cells in S phase, and phosphorylation of RB and cyclin-dependent kinase 2 proteins. In addition, immunohistochemical studies on NPC samples showed that expression of Id-1 was present in NPC cells but absent in normal tissues. This study demonstrates that Id-1 plays an important role in cell proliferation in NPC cells, and our results provide evidence for the first time of the significance of Id-1 expression in NPC cells and suggest a possible role of Id-1 expression in the inactivation of RB and development of NPC. Copyright 2002 Wiley-Liss, Inc.

16
UI - 11893450
AU - Iwai H; Tsuji H; Tachikawa T; Inoue T; Izumikawa M; Yamamichi K;
TI - Yamashita T Neoglottic formation from posterior pharyngeal wall conserved in surgery for hypopharyngeal cancer.
SO - Auris Nasus Larynx 2002 Apr;29(2):153-7
AD - Department of Otorhinolaryngology, Kansai Medical University, 10-15 Fumizonocho, Moriguchi, 570-8506, Osaka, Japan
OBJECTIVE: To describe a new treatment modality of hypopharyngeal cancer consisting of total laryngectomy plus partial pharyngectomy (TLPP) conserving the posterior wall of the pharynx vertically for voice restoration. METHODS: Review of hospital charts, TLPP was undertaken in 15 of 54 patients. Surgical modalities of reconstruction subsequent to TLPP were indicated on the basis of the width of posterior pharyngeal wall conserved during surgery. Posterior pharyngeal walls of width 3 cm or larger were sutured in primary closure. If the width of posterior wall was less than 3 cm, a free forearm flap or free jejunal flap was patched to the wall. Tracheo-esophageal shunt with a voice prosthesis was performed 3 weeks after surgery. RESULTS: The Kaplan-Meier method indicated no difference in survival rate between patients with TLPP (46.4%) and the remaining patients (47.4%). Nine of 15 patients with TLPP (two patients with primary closure, three with free forearm flap, and four with free jejunal flap) were examined for voice restoration and fluoroscopy of the neopharynx. Eight of the nine patients, in whom more than 2 cm of the posterior pharyngeal wall had been conserved, demonstrated a good speech rating, maximum phonation time and neoglottic formation by the posterior pharyngeal wall. CONCLUSION: The combination of conservation of the posterior pharyngeal wall, patch graft and a voice prosthesis is a useful method that offers sufficient quality of phonation without deterioration of survival rate for patients with hypopharyngeal cancer.

17
UI - 11893452
AU - Kuropkat C; Venkatesan TK; Caldarelli DD; Panje WR; Hutchinson J;
TI - Preisler HD; Coon JS; Werner JA Abnormalities of molecular regulators of proliferation and apoptosis in carcinoma of the oral cavity and oropharynx.
SO - Auris Nasus Larynx 2002 Apr;29(2):165-74
AD - Department of Otolaryngology, Head and Neck Surgery, Philipps University, Deutschhausstr. 3, 35037, Marburg, Germany. kuropkat@hno-marburg.de
OBJECTIVE: Abnormalities in genes regulating cell proliferation and death may affect disease outcome in squamous cell carcinoma (SCC) of the head and neck. METHODS: Proliferative activity (Histone H3 in-situ-hybridization (HISH) labeling index (LI)) and the genes and/or gene products of Cyclin D-1, c-erbB-2, Bcl-2, p21, and p53, were investigated in 35 patients with SCC of the oral cavity and oropharynx, previously studied for p27 expression. RESULTS: Overexpression or very low expression of Cyclin D-1 was associated with unfavorable disease outcome and shorter time-to-recurrence. High c-erbB-2 expression was significantly associated with shorter overall survival and was synergistic with low p27 expression. Bcl-2, HISH LI, p21 expression, and p53 mutation and protein analysis were not significantly predictive, but there were trends suggesting shorter disease-free/overall survival for patients with undetectable Bcl-2, high HISH, and mutant p53. CONCLUSIONS: Several cell proliferation and death regulators appeared to predict disease outcome. Limited evidence of cooperativeness among regulators was also seen.

18
UI - 11893453
AU - Fujii M; Yamashita T; Ishiguro R; Tashiro M; Kameyama K
TI - Significance of epidermal growth factor receptor and tumor associated tissue eosinophilia in the prognosis of patients with nasopharyngeal carcinoma.
SO - Auris Nasus Larynx 2002 Apr;29(2):175-81
AD - Department of Otolaryngology, School of Medicine, Keio University, 35 Shinanomachi Shinjuku-ku, 160-8582, Tokyo, Japan. mfujii@mc.med.keio.ac.jp
OBJECTIVE: The expression of epidermal growth factor receptor (EGFR) is one of the indicators, which can predict the malignant potential of squamous cell carcinoma of the head and neck (HNSCC). On the other hand, previous histological studies have proved tumor-associated tissue eosinophilia (TATE) to be a favorable prognostic indicator for HNSCC. We studied the prognostic significance of co-expression of EGFR and TATE. METHODS: We examined the expression of EGFR and TATE in 53 patients with nasopharyngeal carcinoma (NPC). Biopsy specimens were subjected to immunohistochemical-staining for EGFR expression and Luna-staining for TATE. EGFR staining was considered negative when immuno-stained cells were less than 25% in a field. TATE was divided into four grades as grade 0 for 0-2 eosinophils in a high power field, grade 1 for 3-9, grade 2 for 10-29, and grade 3 for 30 or more. RESULTS: In terms of TATE expression, 27 patients were classified as grade 0, 12 as grade 1, six as grade 2, and eight as grade 3. Forty-four patients were EGFR positive and nine were negative. We found no statistical significance in the distribution of EGFR positivity and TATE grades. Among EGFR-positive patients, 5 year survival rates were significantly better in TATE-positive (grades 1, 2, 3) patients than in TATE-negative (grade 0) patients (P=0.0139). CONCLUSION: Eosinophils may be activated in the tumor tissue, in which the expression of EGFR is up-regulated. This suggests that the activated eosinophils in EGFR-positive tumors resulted in better prognoses. TATE infiltration and EGFR expression may be closely related to the malignant potential of NPC, and co-expression of TATE and EGFR may be an important prognostic factor.

19
UI - 12162020
AU - Pajor A; Murlewska A; Jozefowicz-Korczynska M
TI - [Tonsillar carcinoma--clinical assessment and analysis of treatment results]
SO - Otolaryngol Pol 2002;56(3):319-22
AD - Katedra Otolaryngologii i Klinika Laryngologii AM w Lodzi.
The aim of the study was an evaluation of the clinical signs and treatment results of the patients with tonsillar cancer treated in the ENT Clinic Medical University in Lodz during 10 years (1985-1994). In this study we analysed retrospectively the data of 40 subjects (52% of all group 76 patients). Twenty four patients (55%) had tumor with T3-T4 stage and 21 patients (52.5%)--palpable lymph neck nodes. The most frequent treatment modality was combined therapy (surgery with radio/chemotherapy) introduced in 25 persons (62.5%), surgery alone was performed in 10 cases (25%). Distant metastases developed in 6 patients (15%) and the second primary neoplasm in 5 patients (12.5%). We obtained 30% five years survival rate. We stress the importance of careful clinical assessment before planning the treatment.

20
UI - 12369558
AU - Pastore A; Turetta GD; Tarabini A; Turetta D; Feggi L; Pelucchi S
TI - Sentinel lymph node analysis in squamous carcinoma of the oral cavity and oropharynx.
SO - Tumori 2002 May-Jun;88(3):S58-60
AD - Clinica ORL, Universita degli Studi de Ferrara, Italy.
AIMS: The aim of our study was to evaluate the usefulness and applicability of sentinel lymph node (SLN) identification in N0 carcinomas of the oral cavity and oropharynx. STUDY DESIGN: We carried out a prospective evaluation of SLN identification in 20 patients with oral cavity or oropharynx carcinomas with no clinical evidence of lymph node metastases. METHODS: Peritumoral infiltration with technetium-99-labeled nanocolloid followed by lymphoscintigraphy was carried out approximately 18 hours prior to surgery. A vital dye was injected intraoperatively and the SLN was identified with the aid of a gamma probe. All patients underwent routine neck dissection. RESULTS: While multiple radioactive nodes were generally identified on lymphoscintigraphy, the number of nodes ranging from one to five with variable degrees of uptake, intraoperative gamma probe scanning allowed the identification of a single more radioactive lymph node in 19 of the 20 patients. In only one patient did this method lead to the identification of two equally highly radioactive SLNs, with no uptake in the remaining nodes. All SLNs were ipsilateral to the neoplastic lesion. In 15 cases the SLN was tumor negative and so were the remaining nodes obtained by comprehensive neck dissection. In five cases the SLN was the only lymph node containing micrometastasis among those obtained by dissection. There were no instances of node positivity not involving the SLN. CONCLUSIONS: Sentinel lymph node identification in ENT surgery may indicate intraoperatively if node metastasis are present, thereby avoiding overtreatment in a substantial proportion of patients with N0 carcinomas of the oral cavity or oropharynx.

21
UI - 12218867
AU - Truilhe Y; Richaud P; Houliat T; Lagarde P; Demeaux H; Stoll D;
TI - Darrouzet V [Surgical methods of removal of T4 nasopharyngeal malignancies. A preliminary report on 18 cases]
SO - Ann Otolaryngol Chir Cervicofac 2002;119(3):138-45
AD - Service d'ORL, Hopital Pellegrin, C.H.U. Bordeaux, Place Amelie Raba-Leon, 33076, Bordeaux cedex, France.
OBJECTIVES: To describe the technique and evaluate postoperative sequelae and results of transfacial surgical removal of T4N0 nasopharyngeal malignant neoplasms. MATERIAL AND METHODS: Eighteen cases of surgically-treated nasopharyngeal cancers, managed between january 1993 and october 2000, were retrospectively studied. Three patients were non-responders to neoadjuvant chemotherapy, 6 suffered local recurrence following standard treatment and 7 were operated first either because of a huge and osteolytic tumor or because of an uncommon histolopathology. RESULTS: Preoperative Vth nerve neuralgia (8 cases) was alleviated (4 cases) or cured (3 cases). At the time of diagnosis, ophthalmoplegia was observed in 3 cases. It disappeared postoperatively in 2 cases and after following radiation therapy in one. Median follow-up of the series was of 31.8 mths. Four patients were died of disease; one of them from distant metastases 4 years post-surgery. One patient is alive with distant metastases. The 13 last (72.2%) are alive without disease with a 35.6 mths median follow-up (6-77 mths). DISCUSSION: This short and heterogeneous series cannot lead to any evidence-based conclusion. But mid-term free-of-disease survival of 4 of the 5 patients suffering local recurrence and of patients presenting with so-called non-radiation-sensitive tumors is to be considered. In comparison with the high risk of neurological sequels following reirradiation, absence of specific toxicity of surgery observed in this series is to be underlined. CONCLUSION: In selected cases surgical treatment does not demonstrate any toxicity and is able to offer mid-term local control of the disease. Its role is to be evaluated further before inclusion in the therapeutic algorithm of these very bad prognosis-associated tumors.

22
UI - 12227036
AU - Vinnikov AK; Gunchikov MV; Leizerman MG
TI - [Invasive vascular tumor of the oropharynx]
SO - Vestn Otorinolaringol 2002;(3):55-6

23
UI - 12368634
AU - To EW; Lai EC; Cheng JH; Pang PC; Williams MD; Teo PM
TI - Nasopharyngectomy for recurrent nasopharyngeal carcinoma: a review of 31 patients and prognostic factors.
SO - Laryngoscope 2002 Oct;112(10):1877-82
AD - Department of Surgery, The Chinese University of Hong Kong Prince of Wales Hospital, Hong Kong. edwardtowh@yahoo.com
OBJECTIVES/HYPOTHESIS: Nasopharyngectomy is a well-established treatment option for recurrent nasopharyngeal carcinoma. Over a period of 4 years and 3 months, in a total of 43 patients, 45 nasopharyngectomies were performed. Thirty-one patients with follow-up ranging from 12 to 58 months were studied. Twenty-two patients (58%) survived; of these, 18 patients (82%) remained disease free. All patients who developed repeat recurrence or died (n = 12) had a high recurrent T-stage tumor, skull base involvement, multiple recurrences, positive surgical margins, or concurrent neck node metastasis. These factors are poor prognostic parameters and might mitigate the indications for aggressive salvage surgery. However, low recurrent T-stage tumor without neck metastasis carries a good prognosis. Modern minimally invasive surgery carries minimal morbidity.STUDY DESIGN A retrospective study was made to determine prognostic indicators in patients treated with salvage surgery for recurrent nasopharyngeal carcinoma. METHODS: Medical records were analyzed for all patients who had received nasopharyngectomy for nodal metastasis, surgical approach, surgical margins, and pathological nodal status, together with surgical mortality, morbidity, and the delivery of postoperative irradiation, were compared with survival. RESULTS: In all, 43 patients underwent 45 nasopharyngectomies over a period of 4 years and 3 months. Patients with less than 1 year of follow-up were excluded. Four patients with residual disease, who represent a more favorable group, and five patients with planned debulking, nasopharyngectomy, and postoperative stereotactic irradiation were also excluded. The study group comprised 25 men and 6 women (ratio of 4:1) with age ranging from 26 to 69 years (mean age, 49.5 y). In 28 patients (90.3%), the recurrence of nasopharyngeal carcinoma was their first recurrence; in 3 patients (9.7%), the recurrences were second recurrences. Twenty-two patients (71%) survived, achieving a mean survival of 28.5 months. Nine patients died with a mean interval of 7.8 months (range, 1-14 mo). Of the nine patients who died, six (67%) had T3 or T4 tumor, four (44.4%) had concurrent recurrent neck disease, and five (55.5%) had positive surgical margins. Two patients died of perioperative meningitis. Fifteen (83.3%) of the 18 disease-free survivors had a low recurrent T-stage tumor. Mean intervals for development of repeat recurrence or distant metastasis were 16 and 7.9 months, respectively. CONCLUSIONS: High recurrent T stage, skull base involvement, repeated recurrence before surgery, nodal metastasis, and positive surgical margins carry a poor prognosis. This is particularly evident with high T stage and concurrent nodal metastasis. However, patients with low T stage have a survival advantage and benefit most from surgical treatment.

24
UI - 12065105
AU - Levendag PC; Lagerwaard FJ; de Pan C; Noever I; van Nimwegen A; Wijers
TI - O; Nowak PJ High-dose, high-precision treatment options for boosting cancer of the nasopharynx.
SO - Radiother Oncol 2002 Apr;63(1):67-74
AD - Department of Radiation-Oncology, Erasmus Medical Center, Daniel den Hoed Kliniek, Groene Hilledijk 301, Rotterdam, The Netherlands.
PURPOSE: The aim of the study is to define the role and type of high-dose, high-precision radiation therapy for boosting early staged T1,2a, but in particular locally advanced, T2b-4, nasopharyngeal cancer (NPC). MATERIALS AND METHODS: Ninety-one patients with primary stage I-IVB NPC, were treated between 1991 and 2000 with 60-70Gy external beam radiation therapy (ERT) followed by 11-18Gy endocavitary brachytherapy (ECBT) boost. In 1996, for stage III-IVB disease, cisplatinum (CDDP)-based neoadjuvant chemotherapy (CHT) was introduced per protocol. Patients were analyzed for local control and overall survival. For a subset of 18 patients, a magnetic resonance imaging (MRI) scan at 46Gy was obtained. After matching with pre-treatment computed tomogram, patients (response) were graded into four categories; i.e. LD (T1,2a, with limited disease, i.e. disease confined to nasopharynx), LRD (T2b, with limited residual disease), ERD (T2b, with extensive residual disease), or patients initially diagnosed with T3,4 tumors. Dose distributions for ECBT (Plato-BPS v. 13.3, Nucletron) were compared to parallel-opposed three-dimensional conformal radiation therapy (Cadplan, Varian Dosetek v. 3.1), intensity modulated radiation therapy (IMRT) (Helios, Varian) and stereotactic radiotherapy (SRT) (X-plan, Radionics v. 2.02). RESULTS: For stage T1,2N0,1 tumors, at 2 years local control of 96% and overall survival of 80% were observed. For the poorest subset of patients, well/moderate/poorly differentiated T3,4 tumors, local control and overall survival at 2 years with CHT were 67 and 67%, respectively, vs. local control of 20% and overall survival of 12% without CHT. For LD and LRD, conformal target coverage and optimal sparing can be obtained with brachytherapy. For T2b-ERD and T3,4 tumors, these planning goals are better achieved with SRT and/or IMRT. CONCLUSIONS: The dosimetric findings, ease of application of the brachytherapy procedure, and the clinical results in early staged NPC, necessitates ERT combined with brachytherapy boost to be the therapy of preference for LD and LRD. For locally advanced T3,4 tumors, our current protocol indicates neoadjuvant chemotherapy in conjunction with high cumulative doses of radiotherapy (81Gy); IMRT and/or SRT to be the preferred technique for boosting the primary tumor.

25
UI - 12209747
AU - Nguyen TV; Yueh B
TI - Weight loss predicts mortality after recurrent oral cavity and oropharyngeal carcinomas.
SO - Cancer 2002 Aug 1;95(3):553-62
AD - University of Washington School of Medicine, Seattle, WA 98108, USA.
BACKGROUND: The prognosis of patients with recurrent tumors of the head and neck generally is considered poor. Better prediction of outcomes can help physicians counsel patients about the merits of additional treatment. The TNM system, which was created for patients with primary tumors, may not provide optimal information. Anatomic staging systems traditionally have ignored symptom-based variables, such as weight loss, despite their known prognostic value. The objectives of this study were 1) to measure the prognostic impact of weight loss, 2) to evaluate the prognostic value of the TNM staging system, and 3) to create a practical staging system capable of predicting survival after patients develop recurrent tumors of the oral cavity and oropharynx. METHODS: A retrospective chart review was used to identify an inception cohort of patients seeking treatment for recurrent, persistent, and second primary tumors of the oral cavity and oropharynx at the University of Washington. The primary outcome variable was 1-year survival. RESULTS: The 1-year survival rate for the cohort (n = 97 patients) was 38%, with a median survival of 0.7 years. Multivariate analysis (Cox regression) identified weight loss, previous radiation to the head and neck, and TNM stage of the recurrent tumor as factors that had a substantial impact on mortality. A second multivariate technique called conjunctive consolidation was used to determine the relative quantitative impact of each variable on survival and to develop a clinical staging system. Weight loss and previous radiation had the greatest influence, and the use of just these two variables resulted in a three-tiered staging system with 1-year survival rates of 62% (16 of 26 patients), 44% (18 of 41 patients), and 10% (3 of 30 patients). In contrast, the TNM staging system produced survival rates of 60% (patients with Stage I disease), 67% (patients with Stage II disease), 32% (patients with Stage III disease), and 32% (patients with Stage IV disease). CONCLUSIONS: The authors found substantial variation in survival after patients developed recurrent tumors of the oral cavity and oropharynx. Two readily available clinical variables--weight loss and previous radiation--were combined to create a clinically practical staging scheme with more prognostic power than the TNM staging system. Until molecular markers can reliably used be to predict outcomes, greater attention needs to be given to the utility of simple, inexpensive, and surprisingly powerful clinical variables. Copyright 2002 American Cancer Society.

26
UI - 1723647
AU - Mir LM; Belehradek M; Domenge C; Orlowski S; Poddevin B; Belehradek J
TI - Jr; Schwaab G; Luboinski B; Paoletti C [Electrochemotherapy, a new antitumor treatment: first clinical trial]
SO - C R Acad Sci III 1991;313(13):613-8
AD - Unite de Biochimie-Enzymologie de l'I.G.R., U.R.A. n. 147, C.N.R.S., U140 I.N.S.E.R.M., Institut Gustave-Roussy, P.R.I.I., Villejuif.
Electrochemotherapy (ECT) is a new antitumor treatment which consists in delivering electric pulses to the tumor some minutes after an intravenous injection of bleomycin. We report here the first clinical trial of ECT, applied to patients with permeation nodules of head and neck squamous carcinomas. ECT was well tolerated by patients, no serious incident occurred and a clear antitumor efficiency was found.

27
UI - 11702662
AU - Yan J; Fang Y; Jiao Y
TI - [Significance of her2 oncogene expression in primary nasopharyngeal carcinoma]
SO - Zhonghua Yi Xue Za Zhi 2001 Aug 10;81(15):904-6
AD - Cancer Center, Sun Yat-sen University of Medical Sciences, Guangzhou 510060, China.
OBJECTIVE: To investigate the status of her2 oncogene at DNA level and the molecular mechanism of overexpression of her2 oncoprotein in part of patients with nasopharyngeal carcinoma (NPC). METHODS: Forty-five cases of PNC tissue and fifteen cases of no

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