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NCI CANCERLIT^® Search: Pharyngeal Cancer - September 2001

Ultima Vez Modificado: 1 de noviembre del 2001

• [Mandibulotomy for cancer of the oral cavity and oropharynx: functional and carcinologic outcome in 107 cases]

• Alcohol dehydrogenase 3 genotype is not associated with risk of squamous cell carcinoma of the oral cavity and pharynx.

• Diet and risk of oral and pharyngeal cancer. An Italian case-control study.

• [Use of neck platysma myocutaneous flap for reconstruction substance defects after surgical resection of oropharyngeal tumors. Report of 70 cases]

• [Antibiotic prophylaxis in oncologic pharyngolaryngeal surgery: ceftriaxone versus clindamycin and gentamycin]

• Is the 1997 AJCC staging system for nasopharyngeal carcinoma prognostically useful for Chinese patient populations?

• Sentinel node localization in oral cavity and oropharynx squamous cell cancer.

• Prediction of aspiration in patients with newly diagnosed untreated advanced head and neck cancer.

• [Interobserver variability in CT of oro- and hypopharyngeal carcinomas]

• Comparison of CYFRA 21-1 and squamous cell carcinoma antigen in detecting nasopharyngeal carcinoma.

• [Concomitant bifractionated radiotherapy and chemotherapy with cisplatin and 5-fluorouracil in locally progressive, non-resectable epidermoid carcinomas of the pharynx: ten years experience at the Antoine Lacassagne center]

• Epstein-Barr virus (EBV) and human disease: facts, opinions and problems.

• The relationship between length of stay and health-related quality of life in patients treated by primary surgery for oral and oropharyngeal cancer.

• Acquired posterior choanal stenosis and atresia: management of this unusual complication after radiotherapy for nasopharyngeal carcinoma.

• Identification of downstream target genes of latent membrane protein 1 in nasopharyngeal carcinoma cells by suppression subtractive hybridization.

• Changing socioeconomic correlates for cancers of the upper digestive tract.

• Leanness as early marker of cancer of the oral cavity and pharynx.

• [Medical cost analysis of neoadjuvant chemotherapy for advanced tongue and oropharyngeal cancer]

• [Salvage surgery for nasopharyngeal carcinoma after irradiation failure]

• [Preliminary study on the correlation between neovasculature and metastatic nasopharyngeal carcinoma by computer image analysis]

• [Nonepithelial malignant neoplasms of the larynx and hypopharynx]

• Lack of public awareness toward alcohol consumption as risk factor for oral and pharyngeal cancers.

• Human papillomavirus positive squamous cell carcinoma of the oropharynx: a radiosensitive subgroup of head and neck carcinoma.

• The use of a radial forearm hybrid free flap in the reconstruction of a pharyngeal defect on the opposite side.

• The use of brush cytology and directed biopsies for the detection of nasopharyngeal carcinoma and precursor lesions.

• Concomitant twice-a-day radiotherapy and chemotherapy in unresectable head and neck cancer patients: A long-term quality of life analysis.

• [Early diagnosis of nasopharyngeal carcinoma]

• Cisplatin chemotherapy plus adenoviral p53 gene therapy in EBV-positive and -negative nasopharyngeal carcinoma.

• Fractionated stereotactic radiosurgery for 50 patients with recurrent or residual nasopharyngeal carcinoma.

• Oral and pharyngeal cancer: lack of prevention and early detection by health care providers.

• Specific IgA antibodies to recombinant early and nuclear antigens of Epstein-Barr virus in nasopharyngeal carcinoma.

CancerMail from the National Cancer Institute

1
UI - 21134193
AU - Genty E; Marandas P; Beautru R; Schwaab G; Luboinski B
TI - [Mandibulotomy for cancer of the oral cavity and oropharynx: functional and carcinologic outcome in 107 cases]
SO - Ann Otolaryngol Chir Cervicofac 2001 Feb;118(1):26-34
AD - Departement d'ORL et Chirurgie Cervico-faciale, Institut Gustave Roussy, Villejuif.
We report a series of 107 patients who underwent mandibulotomy at the Gustave-Roussy Institute, France for cancer of the oral cavity and orophaynx between 1998 and 1996. The most common tumor site was the base of the tongue. Most cases were stage T2 or T3. Postoperative radiotherapy was employed except in those who had previous irradiation, either for the same tumor (12 cases) or another cancer (16 cases). The different types of mandibulotomies and osteosynthesis methods were analyzed in relation to postoperative course and functional and oncological outcome at mean follow-up of 6 years. Osteitis was the most frequent complication (14%) requiring hemimandibulectomy in 5 cases. Complications occurred particularly when osteosynthesis was in the pre-or postoperative irradiation field. Osteosynthesis was definitive in 79.4% with good functional results in 76.5%. Previous radiotherapy or use of flaps for closure gave poor function results. We emphasize the advantages of anterolateral mandibulotomy and titanium plates. The local control rate was 81.5% at 6 months and overall survival rat was 51.5% at 5 years with no significant impact of tumor site on survival.

2
UI - 21198534
AU - Sturgis EM; Dahlstrom KR; Guan Y; Eicher SA; Strom SS; Spitz MR; Wei Q
TI - Alcohol dehydrogenase 3 genotype is not associated with risk of squamous cell carcinoma of the oral cavity and pharynx.
SO - Cancer Epidemiol Biomarkers Prev 2001 Mar;10(3):273-5
AD - Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Alcohol is one of the major risk factors for oral and pharyngeal cancer. The rate-limiting step in alcohol metabolism is the oxidation (activation) of ethanol to acetaldehyde by the alcohol dehydrogenases (ADHs). It has been hypothesized that individuals who are homozygous for the fast allele (ADH(1-1)(3)) are at greater risk for alcohol-related cancers. To test this hypothesis, we investigated the association between the ADH3 genotype and oral and pharyngeal cancer risk in a large racially homogeneous case-control study of 229 patients and 575 matched control subjects with frequency matching on age, sex, and smoking status. Although the smoking status was matched between cases and controls, current and former alcohol use remained a significant risk factor, compared with never use (odds ratio, 2.08; 95% confidence interval, 1.37-3.17; odds ratio, 1.97; 95% confidence interval, 1.25-3.09; and odds ratio, 1.00, respectively). The ADH1(3) allele frequency of controls was 57.4%, consistent with reports of similar racial groups (50-60%). The genotype distribution in controls was also consistent with the Hardy-Weinberg equilibrium (P = 0.51). However, the ADH1(3) allele frequency and ADH(1-1)(3) genotype frequency were not significantly different between cases and controls [55.5% versus 57.4% (P = 0.52), and 30.6% versus 31.3% (P = 0.91), respectively]. There was no association between ADH3 genotypes (ADH(1-1)(3), ADH(1-2)(3), and ADH(2-2)(3)) and risk of oral and pharyngeal cancer (odds ratios, 1.00; 0.96; 95% confidence interval, 0.68-1.37; and odds ratio, 1.23; confidence interval, 0.78-1.93, respectively). Therefore, we found no evidence that supports a main effect of ADH3 genotype or a combined effect of alcohol and ADH3 genotype on risk of cancer of the oral cavity or pharynx.

3
UI - 21227892
AU - Tavani A; Gallus S; La Vecchi C; Talamini R; Barbone F; Herrero R; Franceschi S
TI - Diet and risk of oral and pharyngeal cancer. An Italian case-control study.
SO - Eur J Cancer Prev 2001 Apr;10(2):191-5
AD - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. tavani@marionegri.it
The relation between diet and risk of oral and pharyngeal cancer was analysed in a case-control study conducted in North-East Italy between 1996 and 1999. Cases were 132 patients (including 33 women), with incident, histologically confirmed cancer of the oral cavity or pharynx, and controls were 148 subjects (including 45 women) admitted to hospitals for acute conditions unrelated to smoking or alcohol drinking. After allowance for tobacco, alcohol and several other potential confounding factors, significant inverse association with the risk of oral and pharyngeal cancer was found for consumption of total green vegetables (OR 0.37) and total fruit (OR 0.34) with significant trends in risk Compared with alcohol drinkers of < 20 drinks/week and eating > 13 portions/week of total green vegetables, the OR for drinkers of > or = 20 drinks/week and eating < 7 portions/week of green vegetables was 15.44. Our study provides further support to the beneficial effect of high intake of vegetables and fruit, particularly in heavy smokers and alcohol drinkers.

4
UI - 21218451
AU - Poissonnet G; Dassonville O; Vallicioni J; Debruyne S; Santini J; Demard F
TI - [Use of neck platysma myocutaneous flap for reconstruction substance defects after surgical resection of oropharyngeal tumors. Report of 70 cases]
SO - Ann Otolaryngol Chir Cervicofac 2001 Apr;118(2):102-9
AD - Departements de Chirurgie ORL et Cervico-faciale, Centre Antoine Lacassagne, 33 avenue de Valombrose, 06189 Cedex 2 et Universite de Nice, Sophia Antipolis, Nice France. gilles.poissonnet@cal.nice.fnclcc.fr
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.

5
UI - 21321918
AU - Subirana FX; Lorente J; Perez M; Quesada JL; Grasa J; Fortuny P; Rosello J; Quesada P
TI - [Antibiotic prophylaxis in oncologic pharyngolaryngeal surgery: ceftriaxone versus clindamycin and gentamycin]
SO - Acta Otorrinolaringol Esp 2001 Mar;52(2):142-5
AD - Servicio de Otorrinolaringologia, Hospital General Universitari del Vall D'Hebron, Universidad Autonoma, Barcelona.
There are many papers comparing two antibiotic protocols for the profilaxis of head and neck infections after laryngeal surgery. We present one prospective and randomised study in 60 patients comparing the efficacy of two protocols. The comparison was between ceftriaxone versus the association of clindamicyn and gentamicyn. In our database we included the risk factors for infection, the surgical approach, the duration of surgery and the patient characteristics. We observed an incidence of 28% of infection, with a 23.3% in the clindamicyn + gentamicyn group and a 33.3% in the ceftriaxone group. The differences between the two groups were not statistically significant. In this study we observed a small difference between the amount of alcohol comsuption, the effectiveness of the surgical drainage, the surgical approach and the presence of wound infection. The difference was not statistical significant due to the small group of patients. The profilaxis was adequate for the total laryngectomy and cordectomy group, with a higher incidence of wound infection in patients treated with a supraglottic laryngectomy.

6
UI - 21376171
AU - Ma J; Mai HQ; Hong MH; Cui NJ; Lu TX; Lu LX; Mo HY; Min HQ
TI - Is the 1997 AJCC staging system for nasopharyngeal carcinoma prognostically useful for Chinese patient populations?
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1181-9
AD - Department of Nasopharyngeal Carcinoma, Cancer Center, Sun Yat-sen University of Medical Sciences, Guangzhou, People's Republic of China. drjunma@hotmail.com
PURPOSE: The 5th edition of the American Joint Committee on Cancer (AJCC) staging manual defines new rules for classifying nasopharyngeal carcinoma (NPC). The study was conducted to assess its effectiveness in predicting the prognosis for Chinese patient populations. METHODS AND MATERIALS: Between June 1993 and June 1994, 621 consecutively admitted patients with nondisseminated NPC were treated with definitive-intent radiation therapy alone. All had computed tomography of the nasopharynx, skull base, and the upper neck. A computer database containing all information for staging was formed on presentation. The extent of disease of each patient was restaged according to the 1997 AJCC system. RESULTS: Of the 621 patients, The 5-year overall survival (OS) rate was 60%. The 1997 AJCC system creates subgroups (Stages I to IV) that are assigned to 38 (6.1%), 270 (43.5%), 157 (25.3%), and 156 (25.1%) patients, respectively. The incidence of parapharyngeal extension was 74.1% (460/621). Of these patients (460) with parapharyngeal extension, 310 (67.4%) patients were classified as T2b disease. The 1997 AJCC system showed highly significant differences between the overall stages for both OS and relapse-free survival (RFS). The 1997 AJCC T classifications showed significant correlation with local failure, and N classification was accurate in predicting FDM. Multivariate analysis showed that paraoropharyngeal involvement was an independently significant prognostic factor for OS, freedom from local recurrence (FLR), and freedom form distant metastasis (FDM). CONCLUSION: The 1997 AJCC staging system for NPC is prognostically useful for Chinese patient populations. We proposed that subdivision of parapharyngeal extension should be included in future revisions of the staging system.

7
UI - 21384652
AU - Taylor RJ; Wahl RL; Sharma PK; Bradford CR; Terrell JE; Teknos TN; Heard EM; Wolf GT; Chepeha DB
TI - Sentinel node localization in oral cavity and oropharynx squamous cell cancer.
SO - Arch Otolaryngol Head Neck Surg 2001 Aug;127(8):970-4
AD - Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA.
OBJECTIVE: To evaluate the feasibility and predictive ability of the sentinel node localization technique for patients with squamous cell carcinoma of the oral cavity or oropharynx and clinically negative necks. DESIGN: Prospective, efficacy study comparing the histopathologic status of the sentinel node with that of the remaining neck dissection specimen. SETTING: Tertiary referral center. PATIENTS: Patients with T1 or T2 disease and clinically negative necks were eligible for the study. Nine previously untreated patients with oral cavity or oropharyngeal squamous cell carcinoma were enrolled in the study. INTERVENTIONS: Unfiltered technetium Tc 99m sulfur colloid injections of the primary tumor and lymphoscintigraphy were performed on the day before surgery. Intraoperatively, the sentinel node(s) was localized with a gamma probe and removed after tumor resection and before neck dissection. MAIN OUTCOME MEASURES: The primary outcome was the negative predictive value of the histopathologic status of the sentinel node for predicting cervical metastases. RESULTS: Sentinel nodes were identified in 9 previously untreated patients. In 5 patients, there were no positive nodes. In 4 patients, the sentinel nodes were the only histopathologically positive nodes. In previously untreated patients, the sentinel node technique had a negative predictive value of 100% for cervical metastasis. CONCLUSIONS: Our preliminary investigation shows that sentinel node localization is technically feasible in head and neck surgery and is predictive of cervical metastasis. The sentinel node technique has the potential to decrease the number of neck dissections performed in clinically negative necks, thus reducing the associated morbidity for patients in this group.

8
UI - 21384653
AU - Rosen A; Rhee TH; Kaufman R
TI - Prediction of aspiration in patients with newly diagnosed untreated advanced head and neck cancer.
SO - Arch Otolaryngol Head Neck Surg 2001 Aug;127(8):975-9
AD - Division of Otolaryngology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ 07103, USA. ROSENAR@UMDNJ.EDU
OBJECTIVES: To determine the prevalence of aspiration in patients with newly diagnosed nontreated advanced head and neck cancer and to determine the ability of the clinical examination to predict aspiration in this patient population. DESIGN: A descriptive prevalence study of the presence of aspiration in patients with advanced (stages III and IV) head and neck cancer and a prospective correlation study between variables of the clinical evaluation with the criterion standard videofluoroscopy. SETTING: Regional veterans affairs medical center. PATIENTS: A consecutive sample of 27 patients without previous treatment or tracheostomy. INTERVENTIONS: All patients underwent evaluation by an otolaryngologist and speech pathologist prior to videofluoroscopy. MAIN OUTCOME MEASURES: Variables in the dysphagia evaluation (consisting of a directed medical history, physical examination, and food challenge), the self-rated 45-item questionnaire, and the clinicians "educated prediction" of aspiration were analyzed with reference to aspiration on videofluoroscopy using univariant analysis. RESULTS: The prevalence of aspiration determined by videofluoroscopy was 41% (11 of 27 patients). Two (6%) of 32 items in the medical history, 1 (4%) of 25 items in the physical examination, and 8 (50%) of 16 items in the food challenge were found to be statistically significantly correlated (P<.05) with aspiration on videofluoroscopy by univariate analysis. Nine (25%) of 45 items in the self-rated questionnaire were correlated with aspiration on videofluoroscopy. The clinicians' educated prediction of aspiration was not correlated with aspiration determined by videofluoroscopy. CONCLUSIONS: Clinical evaluation alone is inadequate in predicting patients who aspirated, determined objectively by videofluoroscopic swallowing study. Further study is needed to develop an efficient dysphagia evaluation to identify patients at risk for aspiration.

9
UI - 21404495
AU - Keberle M; Kenn W; Muller H; Hahn D
TI - [Interobserver variability in CT of oro- and hypopharyngeal carcinomas]
SO - Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 2001 Jul;173(7):583-90
AD - Institut fur Rontgendiagnostik, Universitat Wurzburg. marc.keberle@mail-uni-wuerzburg.de
PURPOSE: To evaluate the inter- and intraobserver reproducibilities of computed tomography (CT) in patients with oro- and hypopharyngeal carcinomas. METHODS: Two independent readers interpreted the CT images of 41 patients with hypopharyngeal carcinomas, 45 patients with oropharyngeal carcinomas, and 23 patients without a tumor. All relevant subregional anatomic structures were evaluated for the presence of tumor infiltration. Statistical analysis was done by using Cohen's kappa and the Wilcoxon test; subregional prevalences, sensitivities, and specificities were also determined. RESULTS: Mostly, especially for clinically relevant subregions, moderate and substantial inter- and intraobserver reproducibilities were determined (range of the determined kappa values: 0.25-1.00). The kappa values of the intraobserver reproducibilities of both readers were not significantly different (P = 0.20). The kappa values of the intraobserver reproducibilities were in almost all the cases higher than the respective kappa values of the interobserver reproducibility. CONCLUSION: CT of oro- and hypopharyngeal carcinomas can be interpreted with clinically acceptable variability. A higher agreement can be achieved if repeated interpretation is done by a single person.

10
UI - 21401501
AU - Lee JK; Hsieh JF; Tsai SC; Ho YJ; Sun SS; Kao CH
TI - Comparison of CYFRA 21-1 and squamous cell carcinoma antigen in detecting nasopharyngeal carcinoma.
SO - Ann Otol Rhinol Laryngol 2001 Aug;110(8):775-8
AD - Department of Nuclear Medicine, China Medical College Hospital, Taichung, Taiwan.
CYFRA 21-1 is a newly developed tumor marker that is especially useful for detecting squamous cell carcinoma (SCC) of the lung. Squamous cell carcinoma antigen is a proven tumor marker that is especially useful for detecting SCC of the cervix. Our aim in this study was to compare the clinical value of CYFRA 21-1 and SCC antigen in the detection of nasopharyngeal carcinoma (NPC). Serum levels of CYFRA 21-1 and SCC antigen were measured in 80 untreated NPC patients and 77 healthy controls. The cutoff values of CYFRA 21-1 and SCC antigen, determined at the 95th percentile of the 77 healthy controls, were 2.48 ng/mL and 1.49 ng/mL, respectively. The results revealed that the mean serum value of only CYFRA 21-1 was significantly higher in the 80 NPC patients than in the 77 healthy controls, and the detection sensitivity of CYFRA 21-1 for NPC was significantly higher than that of SCC antigen. In conclusion, our results suggest that CYFRA 21-1 is a better tumor marker than SCC antigen for detection of NPC.

11
UI - 21413065
AU - Magne N; Pivot X; Marcy PY; Chauvel P; Courdi A; Dassonville O; Poissonnet G; Vallicioni J; Ettore F; Falewee MN; Milano G; Santini J; Lagrange JL; Schneider M; Demard F; Bensadoun RJ
TI - [Concomitant bifractionated radiotherapy and chemotherapy with cisplatin and 5-fluorouracil in locally progressive, non-resectable epidermoid carcinomas of the pharynx: ten years experience at the Antoine Lacassagne center]
SO - Cancer Radiother 2001 Aug;5(4):413-24
AD - Centre Antoine-Lacassagne, 33, avenue de Valombrose, 06189 Nice, France.
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.

12
UI - 21413333
AU - Griffin BE
TI - Epstein-Barr virus (EBV) and human disease: facts, opinions and problems.
SO - Mutat Res 2000 Apr;462(2-3):395-405
AD - Viral Oncology Unit, Imperial College School of Medicine at St. Mary's, Division of Medicine, Norfolk Place, London W2 1PG, UK. b.griffin@ic.ac.uk
The human herpesvirus, Epstein-Barr virus (EBV), has classically been associated with two pathologies with frequencies approaching 100%. One of these, Burkitt's lymphoma (BL), is of B-cell origin and the other, nasopharyngeal carcinoma (NPC), is a tumour of poorly differentiated epithelial cells. More recently, EBV had been identified with frequencies from a few percent to 100% (in one case) with a variety of other malignancies. These include Hodgkin's disease (HD; where in the west, the frequency of association is about 50%), sino-nasal T-cell lymphomas, lymphoepitheliomas, some sarcomas and breast cancers, other cancers from the head and neck, and lymphomas arising in patients with immune dysfunctions. Since EBV is ubiquitous, with the vast majority of the world's population having met and seroconverted to the virus, the diversity of tumours with which it has now been associated represents a substantial health burden. In a recent IARC monograph, EBV was classified as a group 1 carcinogen. Here, the data on BL and NPC, as they relate to geographical restrictions, viral strain variation, co-factors in disease, and genetic components are reexamined. We raise the question whether in their origins, these tumours genuinely reflect distinct and independent events, as deemed at present, or may represent a response by different cell types to common extracellular factors. For example, a situation in Kenya apparently existed in the past, where both BL and NPC were observed in ethnic Africans with roughly equal frequencies; more recently, in Kenya, EBV has been identified in nearly 100% of the tumours in children with HD. We also consider tumours where the viral association is reportedly of low frequency, and offer explanations for these data, including the possibility of loss of the viral genome once malignancy has been initiated. If this phenomenon occurs as a frequent secondary event, EBV could be an even greater health risk than presently believed.

13
UI - 21314489
AU - Rogers SN; Lowe D; Brown JS; Vaughan ED
TI - The relationship between length of stay and health-related quality of life in patients treated by primary surgery for oral and oropharyngeal cancer.
SO - Int J Oral Maxillofac Surg 2001 Jun;30(3):209-15
AD - Regional Maxillofacial Unit, University Hospital Aintree, Aintree Trust, Liverpool, UK. snrogers@globalnet.co.uk
A patient's length of hospital admission is simple to measure, whilst their health related quality of life (HRQOL) is much more challenging. Similar clinical and demographic factors may exist between an increased length of stay (LOS) and a worse HRQOL outcome. The aim of this study was to assess whether LOS could serve as a proxy marker of HRQOL. One hundred and thirty consecutive patients with previously untreated oral and oropharyngeal squamous cell carcinoma were recruited. All had primary surgery. The University of Washington questionnaire (UW-QOL) and the European Organisation for Research and Treatment core cancer questionnaire (EORTC C30) were self-completed preoperatively, after 6 months and 1 year. The median LOS following laser/primary closure/split skin grafts (21 patients) was 2 days compared to 16 days following microvascular free flap reconstruction (105 patients). In the free flap group the best predictors of LOS were age, tumour size and early medical/surgery complications. Patients with a LOS greater than 16 days (median) reported significantly worse chewing (P = 0.008), swallowing (P = 0.002) and cumulative UW-QOL score (P = 0.01). No significant differences were seen in the EORTC C30. Length of stay is potentially a useful indicator of health related quality of life because it is linked by tumour size, however, the relationship is confounded by age, which tends to influence length of stay more than health related quality of life.

14
UI - 21356210
AU - Ku PK; Tong MC; Tsang SS; van Hasselt A
TI - Acquired posterior choanal stenosis and atresia: management of this unusual complication after radiotherapy for nasopharyngeal carcinoma.
SO - Am J Otolaryngol 2001 Jul-Aug;22(4):225-9
AD - Division of Otorhinolaryngology, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.
PURPOSE: To report on acquired posterior choanal stenosis and atresia after radiotherapy for nasopharyngeal carcinoma. MATERIALS AND METHODS: Four patients with acquired bilateral choanal atresia and 2 with severe unilateral choanal stenosis in the posterior choanae were identified after treatment of nasopharyngeal carcinoma with radiotherapy. The mean age was 42 years (range, 29 to 48 years). Two patients had stage II, and 4 had stage III disease, according to Ho's classification. They all received a 66 Gy dose of external irradiation delivered to the nasopharynx, and a mean dose of 62.6 Gy to the neck. Five patients had an additional 20 Gy delivered to the parapharyngeal region, and 1 patient had intracavitatory brachytherapy of 18 Gy delivered to the nasopharynx. The mean onset of symptoms was 10.5 months (range, 2 to 40 months) postirradiation. All patients were treated by transnasal endoscopic resection. Merocel epsitaxis packing (Medtronic Xomed, Jacksonville, FL) was used to stent the nasal airway for 2 weeks postoperatively. RESULTS: The mean follow-up was 16.2 months (range, 14 to 18 months) after surgery. Four patients (67%) were symptom-free. Two patients (33%) had unilateral restenosis in the postnasal space that required revision surgery and further nasal stenting for 2 weeks, and both were subsequently free from further restenosis. No adverse postoperative complication occurred. CONCLUSION: Acquired posterior choanal stenosis and atresia is an unusual long-term complication after radiotherapy that can be successfully treated with transnasal endoscopic resection. A 2-week Merocel nasal stent is recommended to prevent restenosis in the posterior choanae.

15
UI - 21405029
AU - Kwok Fung Lo A; Liu Y; Wang X; Wong YC; Kai Fai Lee C; Huang DP; Tsao SW
TI - Identification of downstream target genes of latent membrane protein 1 in nasopharyngeal carcinoma cells by suppression subtractive hybridization.
SO - Biochim Biophys Acta 2001 Aug 30;1520(2):131-40
AD - Department of Anatomy, Faculty of Medicine, University of Hong Kong, PR China.
Nasopharyngeal carcinoma (NPC) is a common cancer in Southern China and is closely associated with infection of Epstein-Barr virus (EBV). The EBV encoded latent membrane protein 1 (LMP1) is frequently detected in NPC and may play a role in its pathogenesis. Previous studies have shown that LMP1 transformed rodent fibroblasts and altered growth properties in B cells and epithelial cells. However, the pathological role of LMP1 in NPC cells is still poorly understood. In order to investigate the downstream target genes of LMP1 in NPC cells, suppression subtractive hybridization was used to clone and identify the genes differentially expressed in a LMP1 expressing NPC cell line, CNE-2. Two subtractive cDNA libraries were constructed: one enriched for the genes upregulated by LMP1 and one was for the genes downregulated by LMP1. A total of 192 clones were screened by reverse Northern blotting. Fourteen of them were confirmed to be overexpressed while eight of them were suppressed. The upregulation of integrin alpha6, laminin 5gamma2, TAP1 and downregulation of p54nrb, RACK1 and p66Shc were further confirmed in three sets of LMP1 expressing NPC cell lines. The expression profiles of differentially expressed genes identified in this study suggest a role of LMP1 in promotion of cell survival and facilitation of tumor invasion.

16
UI - 21230825
AU - Bosetti C; Franceschi S; Negri E; Talamini R; Tomei F; La Vecchia C
TI - Changing socioeconomic correlates for cancers of the upper digestive tract.
SO - Ann Oncol 2001 Mar;12(3):327-30
AD - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. bosetti@marionegri.it
BACKGROUND: Cancers of the upper digestive tract have long been associated with low socio-economic levels. It has however been suggested that in recent times the social gradient for these cancers is leveling off. PATIENTS AND METHODS: Data from three case-control studies on oral, pharyngeal and oesophageal cancer conducted in Northern Italy during the periods 1984-1992 and 1992-1997 were combined and re-analyzed. Cases were subjects admitted to the major teaching and general hospitals in the areas under study with incident, histologically confirmed cancer of the oral cavity and pharynx (n = 1126) and oesophagus (n = 714). Controls were subjects admitted to the same hospitals for a wide spectrum of acute, non-neoplastic conditions, not related to smoking or alcohol consumption (n = 4642). RESULTS: In the 1980s a significant association was observed with low education and social class level. The multivariate odds ratios for oral, pharyngeal and oesophageal cancers combined was 1.78 for the lowest versus the highest educational level, and 1.75 for the lowest versus the highest social class. No consistent pattern of risk was observed with any of the socio-economic indicators considered in the studies conducted in the 1990s. CONCLUSIONS: The present study indicates that the socio-economic correlates of cancers of the upper digestive tract have changed over the last few years in Italy, with a disappearance of the social gradient.

17
UI - 21230826
AU - Franceschi S; Dal Maso L; Levi F; Conti E; Talamini R; La Vecchia C
TI - Leanness as early marker of cancer of the oral cavity and pharynx.
SO - Ann Oncol 2001 Mar;12(3):331-6
AD - Servizio di Epidemiologia, Centro di Riferimento Oncologico, Aviano (PN), Italy.
BACKGROUND: It is not clear whether the purported association of leanness with cancer of the oral cavity and pharynx was due to cancer-related weight loss or to the influence of factors associated with leanness. PATIENTS AND METHODS: Seven hundred fifty-four incident cases of cancers of the oral cavity and pharynx and 1775 controls, admitted to hospital for acute, non-neoplastic diseases, in Italy and Switzerland. Questionnaire included height, lifetime history of weight and of physical activity, waist and hip measurements, and a validated food-frequency section. RESULTS: Leanness at diagnosis was associated with elevated risk in men (adjusted odds ratio, OR for 5-unit decrease in body-mass index, BMI = 1.9; 95% confidence interval (CI): 1.6-2.2 in men). Male cases were significantly leaner than control subjects at the age of 30 and of 50. Thinner women also had an increased risk, but the inverse association with BMI was non linear. In both sexes, the association with leanness was restricted to smokers and moderate/heavy drinkers, but was not accounted for by drinking and smoking habits, nor by differences in physical activity or dietary habits. CONCLUSIONS: Leanness appears to be an early marker of some unknown biological effect of smoking and/or of alcohol abuse, which may contribute to the prediction of cancers of the oral cavity and pharynx. Cessation of smoking and substantial reduction of alcohol intake may improve nutritional status, besides stopping carcinogen exposure.

18
UI - 21386625
AU - Fujii M; Yamashita T; Ishiguro R; Tashiro M; Ohno Y
TI - [Medical cost analysis of neoadjuvant chemotherapy for advanced tongue and oropharyngeal cancer]
SO - Nippon Jibiinkoka Gakkai Kaiho 2001 Jun;104(6):668-74
AD - Department of Otorhinolaryngology, Keio University School of Medicine, Tokyo.
We performed a medical cost analysis on the use of neoadjuvant chemotherapy (NAC) in multi-modal treatments for advanced tongue and oropharyngeal cancer. Twenty-two patients with stage III and IV squamous cell carcinoma of the tongue and oropharynx were enrolled in this study. Two courses of NAC with CDDP and 5-FU followed by radiotherapy were performed in 13 patients who showed a partial response or a complete response after the first course of NAC. The doses of radiation were 60 Gy for 4 patients (rad. group), and 72 Gy for 9 patients who received hyperfractionated radiotherapy with simultaneous Carboplatin (HF rad. group). Radical surgery was performed in 9 patients who did not respond to NAC (surg. group). The mean duration of hospital stay was 89.3 days for the rad. group, 92.0 days for the HF rad. group, and 113.3 days for the surg. group. The mean medical cost was 238,700 points for the rad. group, 264,846 points for the HF rad. group, and 459,468 points for the surg. group. The mean amounts and percentages of cost for NAC were 39,473 points and 16.1% for the rad. group, 44,802 points and 16.9% for the HF rad. group, and 23,451 points and 5.1% for the surg. group. The mean amounts of cost for NAC including examination costs and nursing costs for chemotherapy were 130,196 points and 54.5% for the rad. group, 150,046 points and 55.7% for the HF rad. group, and 113,839 points and 24.8% for the surg. group. The cost of NAC accounted for half of the total cost of chemo-radiation treatment for functional preservation. The duration of the hospital stay was prolonged by NAC, which accounted for a quarter of the total cost for the surg. group. Survival benefits are considered in the analysis of treatment cost-effectiveness for head and neck cancers. In the future, QOL, which is defined as the utility achieved as a result of multi-modal treatments, should also be analyzed along with survival benefits. Cost-utility analyses should include quality-adjusted life years, based upon the cost identification results of our analysis for NAC, to evaluate the efficacy of NAC in multi-modal treatments for head and neck cancers.

19
UI - 21390888
AU - Xu Z; Tu G; Tang P
TI - [Salvage surgery for nasopharyngeal carcinoma after irradiation failure]
SO - Zhonghua Er Bi Yan Hou Ke Za Zhi 1998 Apr;33(2):103-5
AD - Department of Head and Neck Surgery, Cancer Hospital, Peking Union Medical University, Beijing 100021.
OBJECTIVE: To study the salvage surgery for nasopharyngeal carcinoma after irradiation failure. METHODS: One hundred and twenty-one full-dose-irradiation-uncontrolled cases of nasopharyngeal carcinoma had undergone salvage surgery since 1965 till 1992, in which 41 had primary lesion and 80 neck lesion. All patients received radiation before surgery with the dose of 60Gy-145Gy. The patient selection for this report limited to those with recurrent tumors at the primary sites with no apparent bony involvement and no cranial nerve palsy, or cases with resectable neck recurrences. RESULTS: It showed that palatal fenestration was the best choice of approach for recurrent tumors located at the vault of the nasopharyngeal cavity. When the tumor invaded the parapharyngeal space or, owing to the after-effect of radiotherapy, the patient presented with severe occlusion of the mandible, we preferred the lateral approach through partial mandi-bulectomy. The lateral rhinotomy was only indicated for cases with tumor remnant at the posterior nares. Lymph node excision was performed for cases with single movable node on the neck, and RND for the cases with multiple nodes. The complication rate of after surgery was low (10%), considering the heavy dose of irradiation. The three- and five-year survival rate were 49% (59/121) and 38% (38/100) respectively. CONCLUSION: It suggests that the surgery should be considered as a salvage procedure for cases of nasopharyngeal cancer after irradiation failure. Because of high rate of distant metastasis (62 cases or 45% died after surgery), chemotherapy or other measures should be adopted after local treatment.

20
UI - 21390889
AU - Qian C; Min H; Liang X
TI - [Preliminary study on the correlation between neovasculature and metastatic nasopharyngeal carcinoma by computer image analysis]
SO - Zhonghua Er Bi Yan Hou Ke Za Zhi 1998 Apr;33(2):106-9
AD - Department of Nasopharyngeal Carcinoma, Tumor Hospital, Cancer Center, Sun Yat-sen University of Medical Sciences, Guangzhou 510060.
OBJECTIVE: To investigate the significance of neoangiogenesis in metastasis of nasopharyngeal carcinoma (NPC) so as to clarify further the role of neovascularity in evaluating the prognosis of NPC and the probability of antiangiogenesis in preventing distant metastasis of NPC. METHODS: Fifty-two patients with metastatic NPC were selected and strictly matched in sex, age, T stage, and N stage with another 52 patients with non-metastatic NPC and survived a long time. The tumor tissues of all 104 patients were retrived for computer-assisted, immunohistochemical analysis of tumor vasculature. RESULTS: Counts of microvessel and relative area of all microvessels per image were significantly higher in metastatic NPCs than those of curable, non-metastatic NPCs; while average area of microvessel and average perimeter of microvessel in metastatic NPCs were smaller than those of the opposite. No significant difference in any microvessel parameter had been found among various types of metastasis. CONCLUSIONS: The alterations of microvessel parameters bore significant relationships with metastases of NPC. Evaluation of neovascularity with computer image analysis may help in estimating the prognosis of NPC and in finding out the indications for aggressive multimodal treatments. Angiogenesis inhibitors might be helpful in preventing NPC from distant metastasis.

21
UI - 21390891
AU - Cai X; Wang T; Shi L
TI - [Nonepithelial malignant neoplasms of the larynx and hypopharynx]
SO - Zhonghua Er Bi Yan Hou Ke Za Zhi 1998 Apr;33(2):113-6
AD - First Affiliated Hospital of Shandong Medical University, Jinan 250012.
OBJECTIVES: Nonepithelial Malignant Neoplasms of the larynx and hypopharynx are rare. Their clinical features, diagnosis and treatment were discussed. METHODS: From 1985 to 1996, 23 cases of nonepithelial malignant neoplasms of the larynx and 3 cases of hypopharynx were diagnosed. There were 21 males and 5 females. Age of the patients ranged from 16 to 65 years. Laryngeal tumours included 11 cases of sarcomas, 1 extramedullary plasmocytoma, 9 lymphomas and 2 malignant melanomas. Hypopharyngeal tumours included 1 leiomyosarcoma and 2 malignant melanomas. Extensive resection was the first treatment for 21 patients. Then, according to their histopathologic features, irradiation or/and chemotherapy were chosen. RESULTS: Follow-up period was from 6 months to 10 years. There were 12 patients survived for 4 to 10 years, including 6 cases of laryngeal sarcomas, 2 supraglottic lymphomas, 2 malignant melanomas of the larynx, 1 malignant melanoma and 1 leiomyosarcoma of the hypopharynx. CONCLUSIONS: Characteristics for these tumours were: 1. usually covered by intact mucosa; 2. laryngeal tumours rarely metastasize to the cervical lymph nodes; 3. difficulties in histopathological diagnosis, and immunohistochemistry is helpful to differentiation and determination.

22
UI - 21385795
AU - Mignogna MD; Fedele S; Lo Russo L; Lo Muzio L
TI - Lack of public awareness toward alcohol consumption as risk factor for oral and pharyngeal cancers.
SO - Prev Med 2001 Aug;33(2 Pt 1):137-9

23
UI - 21433639
AU - Lindel K; Beer KT; Laissue J; Greiner RH; Aebersold DM
TI - Human papillomavirus positive squamous cell carcinoma of the oropharynx: a radiosensitive subgroup of head and neck carcinoma.
SO - Cancer 2001 Aug 15;92(4):805-13
AD - Department of Radiation Oncology, Inselspital, University of Bern, Freiburgstrasse 10, 3010 Bern, Switzerland. katja.lindel@insel.ch
BACKGROUND: Epidemiologic evidence points to a connection between viral infection by the human papillomavirus (HPV) and a subgroup of squamous cell carcinoma of the oropharynx. To assess the impact of HPV infection on the response of these tumors toward radiotherapy, the authors retrospectively determined the presence of the virus and the integrity of the viral E2 gene in tumors of patients who have undergone curative irradiation. METHODS: Paraffin embedded biopsies from 99 patients were analyzed for HPV infection and E2 gene integrity by multiplex PCR. The experimental findings were correlated with clinical characteristics, known risk factors, and treatment outcome. RESULTS: Fourteen of 99 tumors were HPV positive (11 HPV16, 1 HPV33, 1 HPV35, and 1 HPV45). Human papillomavirus positivity was closely linked to female gender (odds ratio [OR], 5.75; P = 0.004), age older than 56 years (OR, 7.42; P = 0.012), nonsmokers (OR, 21.33; P = 0.00001), and alcohol abstainers (OR, 5.35; P = 0.012). There was an inverse association with p53 nuclear immunoreactivity (OR, 0.06; P = 0.008). The Kaplan-Meier survival estimates showed a better local control (P = 0.050, log-rank) and a better overall survival (P = 0.046, log-rank) for patients with HPV positive tumors. In the multivariate analysis, HPV positivity remained to be associated with a lower risk of local failure (risk ratio [RR], 0.31; P = 0.048). Four of 11 HPV16 positive tumors had a disrupted E2 gene. Only tumors with a disrupted E2 gene manifested local treatment failure. CONCLUSIONS: Human papillomavirus positivity designates a specific subgroup of oropharyngeal squamous cell carcinomas of the oropharynx that arise preferentially among individuals with no consumption of tobacco and alcohol and that have a favorable outcome attributable to an increased sensitivity toward radiotherapy. Copyright 2001 American Cancer Society.

24
UI - 21331376
AU - To EW; Pang PC; Tsang WS; Ho FN
TI - The use of a radial forearm hybrid free flap in the reconstruction of a pharyngeal defect on the opposite side.
SO - Br J Oral Maxillofac Surg 2001 Aug;39(4):326-7

25
UI - 21336336
AU - Chang AR; Liang XM; Chan AT; Chan MK; Teo PM; Johnson PJ
TI - The use of brush cytology and directed biopsies for the detection of nasopharyngeal carcinoma and precursor lesions.
SO - Head Neck 2001 Aug;23(8):637-45
AD - Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, S.A.R., China.
BACKGROUND: It has been proposed that nasopharyngeal carcinoma (NPC) has an early noninvasive stage, designated nasopharyngeal intraepithelial neoplasia (NPIN). Hence, the detection and treatment of NPIN will prevent NPC from developing, and this would be similar to the strategies used for cervical cancer prevention. We wanted to ascertain the feasibility of using a brush sampler to collect cells for the cytologic diagnosis of NPIN and NPC. If successful, the technique could be used as a screening test in endemic areas. METHODS: A disposable sampler (Uterobrush) was used to collect nasopharyngeal mucosal brushings from 546 patients for cytologic examination. After this, most patients had biopsies, and this allowed histologic-cytologic correlation to be undertaken. RESULTS: In 528 patients (96.7%) there were satisfactory cytologic and biopsy specimens for evaluation. There were 149 cases with positive histology and 103 had positive cytology (specificity was 100% and the sensitivity was 69.1%). One case of NPC with concurrent NPIN was seen among the biopsy specimens, but no case of NPIN was detected cytologically. CONCLUSIONS: The cytologic pickup of NPC was substantially lower than that obtained on biopsy. More importantly, NPIN was uncommon. Therefore, a screening test that depends on the collection of cells for the microscopic diagnosis of NPIN and NPC is unlikely to have a major impact on the incidence of NPC. Furthermore, obtaining a good cytologic specimen from the nasopharynx is not simple, and this further limits this technique for mass screening purposes. The concept of a cytologic test for NPC, similar to the Pap test for the prevention of uterine cervix cancer, has still to be realized.

26
UI - 21336341
AU - Magne N; Marcy PY; Chamorey E; Guardiola E; Pivot X; Schneider M; Demard F; Bensadoun RJ
TI - Concomitant twice-a-day radiotherapy and chemotherapy in unresectable head and neck cancer patients: A long-term quality of life analysis.
SO - Head Neck 2001 Aug;23(8):678-82
AD - Department of Head and Neck Oncology, Centre Antoine Lacassagne, 33 Avenue de Valombrose, 06189 Nice cedex 2, France.
BACKGROUND: The purpose of this study is to make a comparative analysis between acute toxicity with late toxicity. This study is based upon a French quality of life (QoL) questionnaire in a cohort of advanced head and neck (H&N) cancer patients treated by concomitant twice-a-day continuous radiotherapy with no acceleration and chemotherapy with cisplatin and 5-fluorouracil. METHODS: From September 1992 to November 1997, a prospective data bank of 91 patients was constituted. In November 1999, 31 patients were still alive and followed for more than 3 years. All patients had stage IV strictly unresectable squamous cell carcinoma of oropharynx or hypopharynx. A French specific H&N cancer QoL questionnaire was used at the end of radiotherapy and at the last date of follow-up of each patient (during 1999). p values reflect comparison of percentages obtained at the end of treatment with percentages at long-term follow-up. Statistical analysis was performed using chi(2) test (p <.05 considered as significant). Percentages obtained by the QoL questionnaire correspond to moderate-severe problems only. RESULTS: Twenty-nine of 31 (94%) patients participated in the QoL study. Acute treatment toxicities were severe with declines in virtually all QoL and functional domains. Globally, with an average long-term follow-up of 4.5 years (range 3-7 years after treatment), there is a statistical improvement in the following symptoms: dry mouth and sticky saliva (97% versus 55%, p <.05); tasting problems (35% versus 21%, not significant); swallowing problems (77% versus 36%, p <.05); and H&N pain (86% versus 9%, p <.05). Financial problems were not improved (21% versus 14%, not significant), and psychological problems (59% versus 5%) were statistically significant. Fourteen of 29 (48%) patients were drinking and 8 of 29 (28%) were smoking at long-term follow-up; at the diagnosis they were 86% and 90%, respectively. At long-term follow-up 22 of 29 presented good or very good QoL, and 25 of 29 said they had improved their initial QoL. CONCLUSION: The interest of twice-a-day radiotherapy with concomitant chemotherapy is to increase total radiotherapy equivalent dose without increasing late toxicity and also to improve locoregional control, survival, and long-term QoL/effectiveness ratio. Best supportive care is recommended to obtain both good QoL and cancer control in a long-term follow-up.

27
UI - 21349560
AU - Morales-Angulo C; Megia Lopez R; Rubio Suarez A; Bezos Capelastegui JT; Rama J
TI - [Early diagnosis of nasopharyngeal carcinoma]
SO - An Otorrinolaringol Ibero Am 2001;28(3):317-23
AD - Hospital Sierrallana, Torrelavega.
For making an early diagnosis of nasopharyngeal carcinoma it is fundamental to fulfill three requirements. First a high suspicion index based in the knowledge of symptoms and signs of the malady. Secondly it is necessary the routinely use in the consulting room of a nasopharyngoscope. An in third place is to make, in doubtful cases, an enlarged biopsy under endoscopic control and local anesthesia.

28
UI - 21369495
AU - Weinrib L; Li JH; Donovan J; Huang D; Liu FF
TI - Cisplatin chemotherapy plus adenoviral p53 gene therapy in EBV-positive and -negative nasopharyngeal carcinoma.
SO - Cancer Gene Ther 2001 May;8(5):352-60
AD - Department of Experimental Therapeutics, Princess Margaret Hospital/Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
We have previously shown that the introduction of human recombinant wild-type p53 mediated by an adenoviral vector (Ad5CMV-p53), either alone or delivered in combination with ionizing radiation, was cytotoxic to two nasopharyngeal carcinoma (NPC) cell lines. To further explore the potential therapeutic role for gene therapy, the combination of Ad5CMV-p53 and cisplatin was examined in two NPC cell lines, CNE-1 and C666-1. The C666-1 cells are particularly relevant because they express Epstein-Barr virus latent gene products analogous to human NPC in situ. Cells were infected with 5 pfu/cell of Ad5CMV-p53 or Ad5CMV-beta-gal, followed by exposure to increasing doses of cisplatin. Clonogenic and MTT assays were used to assess the sensitivity of cells to these treatments, and apoptosis was also quantified. The combination of Ad5CMV-p53 and cisplatin resulted in approximately 25% greater cytotoxicity compared to that observed with cisplatin alone in either cell line. Apoptosis was induced in approximately 50% of cells following administration of both Ad5CMV-p53 and cisplatin, but was induced in considerably fewer cells following either treatment alone. The two modalities appeared to interact in an additive manner. Ad5CMV-p53 gene therapy resulted in the expression of biologically active p53 protein, shown by induction of p21(WAF1/CIP1). Cisplatin treatment showed little effect on either p53 or p21(W