The association of E-cadherin expression and the methylation status of the E-cadherin gene in nasopharyngeal carcinoma cells.

Loss of E-cadherin (E-cad) has been associated with progression and poor survival in nasopharyngeal carcinoma (NPC). In this study, we investigated the role of methylation on E-cad inactivation in NPC cell lines, as well as in NPC tissue samples. Using 6 NPC cell lines, we found that methylation of the E-cad 5' CpG island promoter region was correlated with the loss of both mRNA and E-cad protein expression in these cell lines. In addition, using 29 NPC and 10 non-malignant nasopharyngeal samples, we also observed 5' CpG methylation of the E-cad gene in 52% (15 out of 29) NPC samples, but in only 10% (1 out of 10) of the non-malignant nasopharyngeal tissues. Our findings indicate that 5' CpG island methylation of the E-cad gene may play an important part in the inactivation of E-cad in NPC. Our results also suggest that reducing the methylation of the E-cad gene may be a potential therapeutic strategy for NPC.

Establishment of two immortalized nasopharyngeal epithelial cell lines using SV40 large T and HPV16E6/E7 viral oncogenes.

Nasopharyngeal carcinoma (NPC) is a common cancer in Southeast Asia, especially in southern China. One of the most striking features of this disease is its close relationship with Epstein-Barr Virus (EBV). However, to date there is no direct study on the mechanisms involved in the role of EBV in the tumorigenesis of NPC, largely due to lack of an experimental model. Available hypotheses on the association between EBV and NPC are generated from non-nasopharyngeal epithelial cell systems such as human keratinocytes or mouse epithelial cells, which may not truly represent the biological properties of nasopharyngeal epithelial (NP) cells. In this study, we report the establishment of two immortalized NP cell lines, NP69SV40T and NP39E6/E7, using SV40T and HPV16E6/E7 oncogenes. We found that NP60SV40T and NP39E6/E7 cell lines not only maintained many characteristics of normal NP cells (i.e. keratin profile and responsive to TGFbeta inhibition) but also highly responsive to one of the EBV encoded genes, LMP1. Comparative genome hybridization (CGH) analysis showed that these two cell lines contained multiple genetic alterations, some of which have been described in NPC. The immortalized NP cell lines are non-tumorigenic and exhibit anchorage-dependent growth. These cell lines may provide a possible cell model system for studying the mechanisms involved in the tumorigenesis of NPC.

Management of extensive cervical nodal metastasis in nasopharyngeal carcinoma after radiotherapy: a clinicopathological study.

OBJECTIVES: To evaluate the efficacy of afterloading brachytherapy following radical neck dissection (RND) in the management of extensive cervical lymph node disease in nasopharyngeal carcinoma after radiotherapy; and to examine prospectively prognostic factors and the pathologic behavior of neck disease. PATIENTS: Twenty-seven patients with nasopharyngeal carcinoma who had extensive cervical lymph node metastasis following external radiotherapy were treated with RND. Thirteen of them also underwent afterloading brachytherapy with iridium wire (Ir 192). The RND specimens of the 27 patients were also examined with step serial whole-specimen sectioning. RESULTS: All patients survived and their wounds healed primarily. Pathologic examination revealed 183 tumor-bearing lymph nodes that contained tumors in the neck: level I, 4% (8/183); level II, 53% (96/183); level III, 34% (62/183); level IV, 5% (9/183); and level V, 4% (8/183). Extracapsular tumor extension was seen in 84% of patients. Multivariate analysis identified the number of tumor-bearing lymph nodes detected in the specimens to be the only significant factor that affected control of disease. Although the neck disease in the group of patients who had afterloading brachytherapy was more extensive, the 3-year actuarial tumor control for the groups with and without brachytherapy were 60% and 61%, respectively. CONCLUSIONS: Recurrent cervical lymph nodes after radiotherapy in nasopharyngeal carcinoma are extensive and RND is mandatory for a successful salvage. When the nodal metastasis infiltrate or adhere to surrounding tissue, afterloading brachytherapy with iridium wire can provide satisfactory local tumor control.

The novel calpain inhibitor SJA6017 improves functional outcome after delayed administration in a mouse model of diffuse brain injury.

A principal mechanism of calcium-mediated neuronal injury is the activation of neutral proteases known as calpains. Proteolytic substrates for calpain include receptor and cytoskeletal proteins, signal transduction enzymes and transcription factors. Recently, calpain inhibitors have been shown to provide benefit in rat models of focal head injury and focal cerebral ischemia. The present study sought to investigate, in experiment 1, the time course of calpain-mediated cytoskeletal injury in a mouse model of diffuse head injury by measuring the 150- and 145-kDa alpha-spectrin breakdown products (SBDP). Secondly, in experiment 2, we examined the effect of early (20 min postinjury) administration of the novel calpain inhibitor SJA6017 on functional outcome measured 24 h following injury and its effect on posttraumatic alpha-spectrin degradation. Lastly, in experiment 3, we examined the effect of delayed (4 or 6 h postinjury) administration of SJA6017 on 24-h postinjury functional outcome. In experiment 1, isoflurane-anesthetized male CF-1 mice (18-22 g) were subjected to a 750 g-cm weight drop-induced injury and were sacrificed for SBDP analysis at postinjury times of 30 min, and 1, 2, 6, 24 and 48 h (plus sham). In experiments 2 and 3, mice were injured as described, and delivered a single tail vein injection of either SJA6017 (0.3, 1, or 3 mg/kg) or vehicle (administered immediately, 4 or 6 h postinjury [3 mg/kg]). Functional outcome was evaluated in both studies, and, in experiment 2, 24-h postinjury assessment of SBDPs was determined. Following injury, the level of SBDP 145 was significantly different from sham at 24 and 48 h in cortical and at 24 h in the hippocampal tissues and at 48 h in the striatum. Immediate postinjury administration of SJA6017 resulted in a dose-related improvement in 24-h functional outcome (p < 0.05 at 3 mg/kg). Significance was maintained after a 4-h delay of the 3 mg/kg, but was lost after a 6-h delay. Despite improvement in functional outcome at 24 h, SJA6017 did not reduce spectrin breakdown in cortical or hippocampal tissues. These results support a role for calpain-mediated neuronal injury and the potential for a practical therapeutic window for calpain inhibition following traumatic brain injury. However, measurements of regional spectrin degradation may not be the most sensitive marker for determining the effects of calpain inhibition.

Microsatellite allelotyping of chinese nasopharyngeal carcinomas.

BACKGROUND: Chinese nasopharyngeal carcinoma (NPC) specimens were analyzed by microsatellite allelotyping to evaluate their usefulness as biomarkers for cancer detection. MATERIALS AND METHODS: A panel of eight microsatellite markers localized to chromosomes 3p, 6p, 9p, I1q and 14q were used to study 47 specimens. RESULTS: A moderately low loss of heterozygosity (LOH) frequency (8% to 35%) was observed; 23 (49%) specimens showed LOH with at least one marker while microsatellite instability (MSI) was detected in 10 specimens (21%). CONCLUSION: Poor survival was significantly associated with LOH detected by a chromosome 3 marker. Interestingly, tumors with multiple genetic alterations were significanty associated with earlier staging

The clinicopathologic significance of p53 and p21 expression in the surgical management of lingual squamous cell carcinoma.

The aim of the present study was to evaluate the clinicopathologic significance of p53 and p21 expression in lingual squamous cell carcinomas. Immunohistochemical staining was performed with p53 and p21 monoclonal antibodies on surgical specimens from 87 patients who underwent primary surgical treatment for lingual carcinoma between 1976 and 1996. We found positive expression of p53 in 45 (52%) of 87 cases and of p21 in 49 (56%) of 87 cases. There was no correlation of p53 and p21 expression with cancer stage, T stage, nodal metastasis, and tumor grade. Univariate analysis revealed that p21 expression, tumor stage, T stage, and nodal stage were significant prognostic factors for survival. However, only p21 expression and tumor stage were significant independent prognostic factors for survival in a multivariate Cox regression analysis. Overexpression of p21 but not p53 has prognostic value for survival in the surgical treatment of lingual carcinomas. The combination of stage with p21 expression is recommended for evaluation of prognosis and for management planning.

Comparative genomic hybridization analysis of nasopharygeal carcinoma: consistent patterns of genetic aberrations and clinicopathological correlations.

To define the patterns of genetic imbalances in nasopharyngeal carcinoma (NPC), we studied 30 primary NPC tumors with comparative genomic hybridization (CGH). The common sites of chromosomal gains were found in descending order of frequency in 12p11.2-p12 (36%), 12q14-q21 (33%), 2q24-q31 (23%), 1q31-qter (20%), 3q13 (20%), 1q13.3 (20%), 5q21 (17%), 6q14-q22 (13%), 7q21 (13%), 8q11.2-q23 (13%) and 18q12-qter (13%). The common sites of chromosomal loss were at 3p14-p21 (20%), 11q23-qter (20%), 16q21-qter (17%) and 14q24-qter (13%). Correlation with clinicopathologic features showed that 3p loss was associated with a significantly higher risk of death related to recurrence as compared with patients without 3p loss (50% vs. 9%, P=.029). The presence of 16q loss was associated with more advanced stage tumors (stages I & II: 6% vs. stages III & IV: 33%, P=.046). We conclude that consistent patterns of genetic imbalances can be observed in NPC. Deletion of 3p and 16q were associated with higher risk of tumor recurrence and advanced stage cancer.

Correlation of endoscopic and histologic findings before and after treatment for nasopharyngeal carcinoma.

BACKGROUND: The endoscopic and histologic findings before and after radiotherapy (RT) for nasopharyngeal carcinoma (NPC) were correlated to study the sensitivity and specificity of endoscopic findings in predicting histologic results. The efficiacy of endoscopic examination and post-RT multiple site biopsies in detecting persistent disease was also evaluated. METHODS: Seven hundred forty-six patients were evaluated. Pre-RT, biopsies were taken from both sides of the nasopharynx to assess the extent of tumor. Four to 16 weeks after RT, routine six-site biopsy specimens were taken from both roofs, lateral, and posterior walls of the nasopharynx and repeated 2 weeks later. Endoscopic findings of exophytic growth, nodule, ulcer, and submucosal bulge were considered "residual tumor," others were considered "no residual tumor." Persistent disease was defined as positive histologic findings 12 weeks after RT. RESULTS: Before RT, sensitivity of endoscopic findings and biopsy specimens in detecting malignancy were 99.7% and 94.2%, respectively. After RT, sensitivity and specificity of endoscopic findings in predicting positive histologic findings were 29% and 85.8%, respectively, with a positive predictive value of 34.9% and a negative predictive value of 82.2%. Of positive histologic findings, 27.7% were missed in the first session of biopsies; 33.5% of those with positive histologic findings turned out to have persistent disease. For prediction of persistent disease, the sensitivity and specificity of endoscopic findings were 40.4% and 84.4%, with a positive predictive value of 16.3% and a negative predictive value of 95%, and that of histologic findings in the first session of biopsies were 59.6% and 88.3%, respectively, with a positive predictive value of 27.7% and a negative predictive value of 96.7%. CONCLUSIONS: Endoscopic findings alone have low sensitivity in predicting persistent disease, multiple sites biopsy specimens are indicated. Because only 1.9% of patients with endoscopic findings of "no residual tumor" and negative histologic findings in first session of biopsies had persistent disease, this group can be spared second biopsies. Repeat biopsies are indicated for those with endoscopic findings of "residual tumor" or positive histologic findings in first session of biopsies to improve detection of persistent disease.

Relationship between the size of neopharynx after laryngectomy and long-term swallowing function: an assessment by scintigraphy.

OBJECTIVES: To study the relationship between the size of neopharynx after total laryngectomy and long-term swallowing function by means of scintigraphy. STUDY DESIGN: The width of pharyngeal remnant was measured during surgery in 11 patients. Their swallowing function was assessed by scintigraphy 8 to 10 years after surgery. METHODS: The width of pharyngeal remnant at its narrowest point in both relaxed and stretched state was measured during surgery. Postoperative scintigraphy data on swallowing were obtained and computed along 3 lines, (1) transit time through neopharynx, (2) percentage of bolus transferred, and (3) swallowing efficiency. The relationship between the 2 sets of data was analyzed by linear regression analysis. RESULTS: (1) No statistically significant relationship was found between the size of neopharynx and swallowing function. (2) All patients are clinically asymptomatic. CONCLUSIONS: The swallowing function is not affected by the size of the neopharynx in 11 patients with pharyngeal remnant width ranging from 3 to 8 cm (stretched).

Downregulation of hemidesmosomal proteins in nasopharyngeal carcinoma cells.

Hemidesmosome (HD) is a transmembrane complex that mediates attachment of epithelial cells to the basement membrane. Abnormal expression of HD components has been reported in several types of human cancers and is believed to play a role in tumor invasion and metastasis. Using differential gene display, we have identified downregulation of BPAG1 expression in nasopharyngeal carcinoma cells. BPAG1 is a major component of hemidesmosome. In the present study, we have extended our work to investigate the expression pattern of other components in the HD complex, namely, BPAG2, ITGalpha6 and ITGbeta4 in three distinct biological groups of nasopharyngeal epithelial cells: (a) non-malignant nasopharyngeal epithelial cells established from primary culture of nasopharyngeal explants, (b) non-malignant nasopharyngeal epithelial cells immortalized by viral oncogenes, SV40 or HPV16E6E7, and (c) nasopharyngeal carcinoma (NPC) cells. Both non-malignant primary cultured nasopharyngeal epithelial cells and immortalized nasopharyngeal epithelial cell lines expressed all the HD components examined, although the immortalized cells expressed a lower level of HD components compared with the non-malignant nasopharyngeal cells established from primary culture. In contrast, downregulation of HD components is commonly observed in nasopharyngeal carcinoma cells. Loss of HD expression in NPC may be associated with the undifferentiated properties of NPC cells and may have prognostic significance.

Microsatellite alterations in squamous cell carcinoma of the head and neck - clustering of loss of heterozygosity in a distinct subset.

Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been recognized as important events in the carcinogenesis of many cancers, including squamous cell carcinoma of head and neck (SCCHN). However, microsatellite alterations have not been documented in SCCHN from Chinese patients. We investigated the frequency and clinical significance of LOH and MSI in 30 SCCHN from Hong Kong Chinese using polymerase chain reaction on 17 microsatellite markers on chromosomes 3p, 4q, 7q, 9p, 17p and 18q. LOH was present in nine tumours (30%) and MSI in four (13%). The incidence of LOH (7/13; 53.8%) in hypopharyngeal-laryngeal cancers was significantly higher than that (2/17; 11.8%) in the oral cancers (P=0.020). LOH was more often detected at the loci on chromosomes 7 and 9. Patients with tumours having LOH had slightly poorer outcome compared with those without, although the differences did not reach statistical significance. Our data show that the incidence of microsatellite alterations in SCCHN from Hong Kong Chinese is low. However, LOH may be one of the genetic mechanisms in the carcinogenesis of a subset of SCCHN (hypopharyngeal-laryngeal cancers).

Differential gene expression in nasopharyngeal carcinoma cells.

Nasopharyngeal carcinoma (NPC) is a common cancer among southern Chinese. The profile of gene expression in NPC cells is largely unknown. In this study, we have examined differential gene expression in non-malignant and malignant nasopharyngeal epithelial (NPE) cells using a cDNA array hybridization method. A total of 42 genes were identified to be expressed in either non-malignant and malignant NPE cells or both. Thirteen of these genes were overexpressed in malignant NPE cells. These includes nuclear factor (NF90), FOS-related antigen 1 (FRA- 1), cytoplasmic dynein light chain (HDLC1), replication factor C (RFC1), nucleoside diphosphate kinase B, UV excision repair protein (RAD23A), insulin-like growth factor receptor II, transcription initiation factor TFIID subunit (TAFII31), growth factor receptor-bound protein 2 (GRB2), UV excision repair protein (RAD23B), glutathione peroxidase, Y box binding protein 1 and heat shock protein 86. In contrast, expression of nine genes was suppressed in malignant NPE cells. These includes calgranulin A, calgranulin B, neutrophil activating protein (ENA-78), heat shock protein 27, integrin beta-1, integrin beta-4, cyclin-dependent kinase inhibitor 1A (p21), interleukin-8 and tyrosine protein kinase receptor (RET). Differential expression of calgranulin A, calgraunlin B, ENA-78, FRA-1 and NF90 in non-malignant and malignant nasopharyngeal epithelial cells was confirmed by RT-PCR analysis.

Subtype-selective N-methyl-D-aspartate receptor antagonists: benzimidazalone and hydantoin as phenol replacements.

Previous work in our laboratories investigating compounds with structural similarity to ifenprodil (5) and 6 (CP101,606) resulted in compound 7 as a potent and selective antagonist of the NR1/2B subtype of the NMDA receptors. Replacement of the phenol group of 7 with a benzimidazalone group tethered by a three-carbon chain to 4-benzylpiperidine resulted in a slightly less active, but selective, compound. Lengthening the carbon tether resulted in a decrease in NR1/2B potency. Replacement of the phenol ring with a hydantoin resulted in weak antagonists. Compound 11a was one of the most potent NR1/2B antagonists from this study. Compound 11a also potentiated the effects of L-DOPA in a rat model of Parkinson's disease (the 6-hydroxydopamine-lesioned rat), dosed at 30 mg/kg orally.

A prospective evaluation of recurrent laryngeal nerve paralysis during thyroidectomy.

HYPOTHESIS: Recurrent laryngeal nerve paralysis after thyroidectomy can be unrecognized without routine laryngoscopy, and patients have a good potential for recovery during follow-up. DESIGN: A prospective evaluation of vocal cord function before and after thyroidectomy. Periodic vocal cord assessment was performed until recovery of cord function. Persistent cord palsy for longer than 12 months after the operation was regarded as permanent. SETTING: A university hospital with about 150 thyroid operations performed by 1 surgical team per year. PATIENTS: From January 1, 1995, to April 30, 1998, 500 consecutive patients (84 males and 416 females) with documented normal cord function at the ipsilateral side of the thyroidectomy were studied. MAIN OUTCOME MEASURES: Vocal cord paralysis after thyroidectomy. RESULTS: There were 213 unilateral and 287 bilateral procedures, with 787 nerves at risk of injury. Thirty-three patients (6.6%) developed postoperative unilateral cord paralysis, and 5 (1.0%) had recognizable nerve damage during the operations. Complete recovery of vocal cord function was documented in 26 (93%) of 28 patients. The incidence of temporary and permanent cord palsy was 5.2% and 1.4% (3.3% and 0.9% of nerves at risk), respectively. Among factors analyzed, surgery for malignant neoplasm and recurrent substernal goiter was associated with an increased risk of permanent nerve palsy. Primary operations for benign goiter were associated with a 5.3% and 0.3% incidence (3.4% and 0.2% of nerves at risk) of transient and permanent nerve palsy, respectively. CONCLUSIONS: Unrecognized recurrent laryngeal nerve palsy occurred after thyroidectomy. Thyroid surgery for malignant neoplasms and recurrent substernal goiter was associated with an increased risk of permanent recurrent nerve damage. Postoperative vocal cord dysfunction recovered in most patients without documented nerve damage.

Clinicopathological significance of p53 and p21 expression in the surgical treatment of laryngeal carcinoma.

BACKGROUND: This study aimed at resolving the clinicopathological significance of p53 and p21 expression in patients undergoing surgical treatment for laryngeal carcinoma. MATERIALS AND METHODS: p53 and p21 expression were studied by immunohistochemical method on surgical specimens of 193 patients. The expressions of p53 and p21 were correlated with the clinicopathological data. RESULTS: Of the 193 tumors, 60% had positive p53 expression and 46% had positive p21 expression. Nodal metastasis was significantly correlated with p53 overexpression, supraglottic involvement and moderate- to poor-differentiation of the tumor. There was significant cumulative effect with increasing risk of nodal metastasis with increasing number of risk factors: 0% without any risk factor, 13% with 1 risk factor, 37% with 2 risk factors and 55% with all 3 risk factors. CONCLUSION: Positive expressions p53 and p21 were common in laryngeal carcinoma. Overexpression of p53 but not p21 was associated with nodal metastasis. The use of p53 expression has added value in providing more accurate prognostic analysis of risk of nodal metastasis in conjunction with site of tumor involvement and tumor grade.

Malignant otitis externa caused by Malassezia sympodialis.

BACKGROUND: Malignant otitis externa caused by fungal infections is rare. A review of the literature showed only 9 cases, and the causative fungus in all cases was Aspergillus. This article reports an unusual case caused by Malassezia sympodialis. METHODS: A 53-year-old man with non-insulin dependent diabetes presented with malignant otitis externa. He deteriorated despite treatment with intravenous antipseudomonal therapy and surgical debridement. Microbiologic tests revealed M. sympodialis. He responded rapidly to intravenous amphotericin. RESULTS: Systemic human infections caused by M. sympodialis have not been reported. M. furfur systemic infection is rare and has been associated lipid hyperalimentation by means of a central catheter. Only 1 other case of M. fungemia without these associated risk factors has been reported. CONCLUSIONS: The first case of malignant otitis externa caused by M. sympodialis is presented. It highlights the difficulty of initial biologic diagnosis and the need for lipid-enriched media to grow this fastidious organism.

Structure-activity relationship of N-(phenylalkyl)cinnamides as novel NR2B subtype-selective NMDA receptor antagonists.

A novel series of N-(phenylalkyl)cinnamides related to N-(4-phenylbutyl)-3,4-dihydroxy-beta-cyanocinnamide (6, an EGFR-K inhibitor with high antiproliferative activity) was synthesized and tested for antagonism at N-methyl-D-aspartate (NMDA) receptor subtypes. Potency and subunit selectivity were assayed by electrical recordings in Xenopus oocytes expressing three binary combinations of cloned rat NMDA receptor subunits: NR1A expressed in combination with either NR2A, NR2B, or NR2C. The N-(phenylalkyl)cinnamides are selective antagonists of NR1A/2B receptors. Assayed under steady-state conditions, N-(4-phenylbutyl)-4-hydroxycinnamide (16) has an IC(50) value of 77 nM and >1000-fold selectivity with respect to NR1A/2A and NR1A/2C receptors. Potency at alpha(1) adrenergic receptors is low for the four cinnamides tested. Inhibition of NR1A/2B receptors does not correlate with EGFR and ErbB2/neu tyrosine kinase inhibitor activity. The N-(phenylalkyl)cinnamide series we describe provides a novel and structurally diverse framework for designing new NR2B-selective NMDA antagonists as potential CNS therapeutics.

The time course of histologic remission after treatment of patients with nasopharyngeal carcinoma.

BACKGROUND: The objective of this study was to define the time course of histologic remission and to evaluate the prognostic significance of delayed histologic remission of patients with nasopharyngeal carcinoma (NPC). METHODS: Between 1986-1994, 803 patients underwent serial postradiotherapy nasopharyngeal biopsies. Patients with positive histology underwent repeated biopsies every 2 weeks until the biopsies were found to be negative or, if remission did not occur by the 12th week after radiotherapy, treatment was initiated for persistent disease. Patients with positive histology found after the fifth week but who achieved spontaneous remission before the twelfth week were considered to have delayed histologic remission. Negative histology by the sixth week was considered early histologic remission. The outcome of patients with delayed histologic remission, early histologic remission, and persistent disease were compared. RESULTS: Six hundred and seventeen patients (76.8%) had negative histology within 12 weeks of the completion of radiotherapy and 55 (6.9%) had persistent disease at Week 12. In 131 patients (16.3%) spontaneous remission was observed in repeat biopsies after initial positive histology. With increasing time after radiotherapy, the incidence of positive histology decreased but more patients were found to have persistent disease. Patients with early and delayed histologic remission had 5-year NPC control rates of 82.4% and 76.8%, respectively (P = 0.35) versus a 40% NPC control rate among patients with persistent disease (P < 0.001). The 5-year survival rates were 75.3%, 79.4%, and 54.2%, respectively, for the 3 groups (P < 0.001). CONCLUSIONS: A high proportion of early positive histology remitted spontaneously. Delayed histologic remission in NPC patients is not a poor prognostic factor and additional treatment is not necessary. A confirmatory biopsy at 10 weeks is recommended before the initiation of salvage treatment.

Identification of genes differentially expressed in nasopharyngeal carcinoma by messenger RNA differential display.

We have applied the mRNA differential display method to compare and analyze mRNAs prepared from five normal nasopharyngeal epithelial cell cultures and five nasopharyngeal carcinoma cell lines. A total of 24 differential display experiments was performed using different combinations of PCR primers. Sixty-nine cDNA fragments differentially expressed in either normal or malignant nasopharyngeal epithelial cells were identified. Subsequent cloning and sequencing of these differentially expressed cDNA fragments resulted in the identification of seventeen distinct sequences. Seven of these sequences were shown to be novel cDNA sequences not previously reported. Ten of the remaining cDNA fragments showed sequence homology to previously reported genes. Differential expression of four of these seventeen cDNA fragments in normal nasopharyngeal epithelial cells was confirmed by reverse Northern hybridization. One of these cloned cDNA fragments is a novel cDNA sequence while the other three matched to previously reported cDNA sequences involved in cell growth and migration. Homologous sequences identified to be differentially expressed in normal nasopharyngeal epithelial cells in this study are: human 26 kDa cell surface protein (TAPA-1) mRNA, NF-E2 like basic leucine zipper transcriptional activator and the human bullous pemphigoid antigen. The mRNA differential display is a useful tool to identify candidate genes involved in the pathogenesis of nasopharyngeal carcinoma.

Current status of pharyngolaryngo-esophagectomy and pharyngogastric anastomosis.

BACKGROUND: Pharyngolaryngo-esophagectomy and pharyngogastric anastomosis (PLO & PGA) is one of the surgical options in the management of tumors arising from the hypopharynx and cervical esophagus. Indications of the operation and the outcome are changing over the years. To examine these, the experience of this operation in one Institute (the Head and Neck Division of the Department of Surgery, The University of Hong Kong at Queen Mary Hospital, Hong Kong) over the last 30 years was reviewed. METHODS: From 1966 to 1995, a total of 317 patients underwent PLO & PGA. The clinical results of 69 patients operated on between 1986 and 1995 were analyzed and compared with those of the two groups of patients reported previously from the same Institute to establish the current status of PLO & PGA. RESULTS: The demographic data of three groups of patients were similar. In previous years, 53% of the primary tumors were advanced laryngeal carcinomas extending to the hypopharynx, whereas the other 47% originated from hypopharyngeal and cervical esophageal regions. In recent years, all patients belonged to the latter group. CONCLUSIONS: The hospital mortality has decreased from 31% to 9%, and the incidence of morbidity such as anastomotic leakage and bleeding has also been reduced, from 20% to 10%. This may be related to the introduction of transthoracic endoscopic mobilization of the esophagus and patient selection. The overall minor morbidity has, however, remained at about 49%, and the 5-year actuarial survival rate has improved, from 18% in the 1970s to 24.5% at present.