Head and neck reconstruction using microsurgery: a 9-year retrospective study.

A total of 137 patients diagnosed with head and neck cancer underwent ablative surgery and primary free flap reconstruction during a period of 9 years, 2001-2009 (men 73.7 %, women 26.3 %). Surgery included a multidisciplinary approach involving plastic, head and neck, and maxillofacial surgeons. Squamous cell carcinoma (SCC) represented the vast majority of the diagnosed tumors (91.2 %); other tumors represented in the study were malignant melanoma, sarcoma, adenocarcinoma and blastoma. The free flaps (n = 143) used for reconstructive surgery included radial forearm flap (n = 128), fibular flap (n = 13) and rectus abdominis muscular flap (n = 2). Twenty patients (15 %) needed reoperation within 48 h due to clinical signs of hematoma (n = 8) and free flap ischemia (n = 12). Furthermore, we report a total of 12 free flap failures, giving an overall free flap success rate of 92 %. Five patients were treated due to infections at donor site (4 %). The overall survival rate (OS) in male patients diagnosed with oral SCC stage II-IV after 2 and 5 years was 82 and 78 %, respectively. Female patients in the same group displayed a 2- and 5-year OS of 78 and 67 %, respectively. Furthermore, analysis of patients treated for recurrence of primary SCC displayed a 2- and 5-year OS of 70 and 55 %, respectively. We conclude that our multidisciplinary approach and treatment algorithm for head and neck cancer including primary free flap reconstruction reconstitutes a safe and reliable tool.

Gene expression profile in oral squamous cell carcinomas and matching normal oral mucosal tissues from black Africans and white Caucasians: the case of the Sudan vs. Norway.

Expression profile of 588 known genes relating to tumour biology, was examined between oral squamous cell carcinomas (OSCCs) and matching normal oral mucosal tissues (NOMTs) obtained from Sudanese (n=11) and Norwegian (n=11) patients. cDNA probes were synthesised from total RNA and hybridised with the Atlas human cancer cDNA expression array membranes. RT-PCR and immunohistochemistry were applied to confirm the expression pattern of a subset of the 588 genes. Differences in expression of the genes examined were found between the OSCCs and the NOMTs on the Atlas membranes. Several of these genes were either up- or down-regulated 1.6-fold or higher in the OSCCs compared to the NOMTs in the cases from the two populations. We found that 181 (31%) and 195 (33%) genes were either up-regulated or down-regulated in the OSCCs from the Sudan and Norway, respectively. From the total number of genes (n=376) found expressed in the OSCCs investigated from the two countries, 53 genes (14%) showed common expression profile [35 (66%) were up-regulated and 18 (34%) were down-regulated] and 70 genes (19%) showed opposite regulation status. Results of the RT-PCR and immunohistochemistry confirmed the hybridisation data. These findings may provide an OSCCs-specific gene expression profile in patients from the two countries, suggesting that alterations of 123 genes are common in these OSCCs regardless of ethnic differences or other socio-cultural risk factors between the patients from the two countries. The findings might further suggest that specific genes are frequently involved in these OSCCs, which may provide novel clues as diagnostic, prognostic biomarkers and/or targets for therapy. The Atlas human cancer cDNA expression array technique can be useful to examine and describe the expression profile of known genes frequently involved in OSCCs from different populations.

Maintained CD40 and loss of polarised CD40 ligand expression in oral squamous cell carcinoma.

BACKGROUND: CD40 and its ligand (CD40L) are involved in immune response and inhibition or induction of apoptosis in different tissues. Little is known about CD40 and CD40L in oral squamous cell carcinomas (OSCC). MATERIALS AND METHODS: CD40 and CD40L were immunohistochemically evaluated in fresh-frozen samples of OSCC (n = 24) and normal oral epithelium (OE, n = 10). RESULTS: A high proportion of OE-cells expressed CD40 (> 80%) and CD40L (> 90%) in the basal compartment compared to less than 1% CD40-positive and 1% CD40L-positive cells in the suprabasal cell layer, reflecting a zonal distribution. In well-differentiated and moderately-differentiated OSCC, there was a less pronounced zonal distribution of CD40 and a marked loss of CD40L compared to OE (p < 0.05). Poorly-differentiated OSCC maintained CD40 and markedly lost CD40L compared to OE (p < 0.05). Double immunostaining for CD40L and laminin in OE showed a basement membrane associated localisation of CD40L. CONCLUSION: In OSCC, loss of polarised expression of CD40L and maintained expression of CD40 might be involved in tumourigenesis and immune evasion.

Epstein Barr virus genome in nasopharyngeal carcinomas from New Zealand.

BACKGROUND: The population in New Zealand is a heterogeneous mix of Caucasians (80%), Maori (9%), and Polynesians (10%). It is believed that the Polynesians are of Chinese descent and may harbor the same high incidence of nasopharyngeal carcinoma (NPC). In addition, it is not known whether the Epstein-Barr virus (EBV) is as closely associated with the development of NPC in Polynesians as it is in those of Chinese origin. METHODS: This study reexamines the associative correlation between EBV and NPC with two methods of genetic detection, polymerase chain reaction (PCR) and in-situ hybridization (ISH). In addition, geographic heterogeneity was analyzed to determine whether there are differences in the prevalence of EBV in NPCs among the ethnic mixed populations found in New Zealand. Nasopharyngeal biopsy specimens from 20 patients with NPC and 36 controls were obtained from Auckland. RESULTS: With PCR, EBNA-1, a genomic sequence of EBV in NPC samples was able to be detected with 76.5% sensitivity and 96.7% specificity. By use of ISH, EBV was detected in NPC tissue with 82.4% sensitivity and 100% specificity. CONCLUSION: There seems to be no geoanthropologic differences in terms of the association of EBV with NPC.

Oral squamous cell carcinoma is associated with decreased bcl-2/bax expression ratio and increased apoptosis.

Expression of bcl-2 and bax and apoptosis were studied in fresh frozen samples of normal oral epithelium (OE, n = 7) and oral squamous cell carcinomas (OSCC, n = 16) by immunohistochemistry and the TUNEL method. In OE, bcl-2 was expressed in both basal (96.6% +/- 2.3% [mean +/- SD]) and suprabasal (91.8% +/- 6.2%) compartments. In OSCC, compared with OE, there was a marked reduction of bcl-2-positive cells in the basal part, and in the central parts of well-differentiated (33.0% +/- 19.7%, P < .001) and moderately differentiated (6.1% +/- 4.6%, P < .001) and also in poorly differentiated (1.9% +/- 0.2%, P < .001) tumors. More cells expressed bax in the suprabasal layer of OE (65.6% +/- 9.9%) and central parts of OSCC than in the basal layer of OE (19.1% +/- 4.1%) and basal parts of OSCC. A higher proportion of cells expressed bax in the central part of well-differentiated OSCC (74.3% +/- 8.2%) than in poorly differentiated OSCC (24.9% +/- 9.7%, P < .001). Apoptotic cell death was more pronounced in OSCC (1.5% +/- 0.9%) than in OE (0.4% +/- 0.1%, P < .05). We conclude that, in OSCC, compared with OE, there is a decreased bcl-2 expression, a lowered bcl-2/bax ratio and increased apoptosis. The expression of bax correlates with histological tumor grading in oral squamous cell carcinoma.

Nasopharyngeal brush biopsies and detection of nasopharyngeal cancer in a high-risk population.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is an important tumor in many countries. Ethnic and regional factors strongly influence disease risk. NPC is usually diagnosed late in disease development, and 10-year survival rates are as low as 10%. Epstein-Barr virus (EBV), a possibly causative agent, is present in all cells of essentially all undifferentiated NPCs. We wished to determine the following: 1) whether an ambulatory nasopharyngeal brush biopsy could provide sufficient tumor cell DNA for the detection of EBV and 2) whether the detection of EBV in this locale reflects the presence of tumor cells or simply EBV carrier status. METHODS: We collected nasopharyngeal tissue via ambulatory brush biopsies from 21 patients with newly diagnosed NPC and from 157 subjects with other otolaryngologic complaints. The majority of study subjects were from high-risk populations. Sample DNA was analyzed for the presence of EBV genomic sequences by use of the polymerase chain reaction (PCR). RESULTS: Ninety-six percent of samples yielded sufficient DNA for PCR amplification. Nineteen of 21 patients with NPC brushed positive for EBV DNA, while all but two (1.3%) of 149 informative control subjects were negative for EBV (two-sided P<.0001). One of the EBV-positive control subjects had an EBV-positive inverted sinonasal papilloma; the other EBV-positive control subject exhibited no overt clinical disease. CONCLUSION: Demonstration of EBV DNA in nasopharyngeal brush biopsy specimens detects NPC with a sensitivity of at least 90% (95% confidence interval = 89.63%-91.32%) and a specificity of approximately 99% (95% confidence interval = 98.64%-98.68%). This technique merits further testing as a possible ambulatory screening strategy in high-risk populations.

Suppression of Fas receptor and negative correlation of Fas ligand with differentiation and apoptosis in oral squamous cell carcinoma.

Apoptosis and the expression of Fas receptor (Fas) and Fas ligand (FasL) were studied in 8 samples of normal oral mucosa (OM) and in 19 oral squamous cell carcinomas (OSCC) by immunohistochemistry and the TUNEL method. Fas was detected in less than 2% of cells in OSCC compared with 84.3+/-9.0% of cells in the basal layer in OM. FasL was found to be highly expressed in poorly differentiated lesions (90.9+/-3.6%), and in cells of both the basal (88.3+/-4.3%) and central (85.3+/-5.7%) parts of moderately differentiated lesions, whereas in well-differentiated (WD) lesions expression was considerably lower in both basal (42.7+/-4.1%) and central (11.5+/-2.4%) parts. In normal OM FasL was primarily detected in cells of the basal layer, but in a high proportion of cells (84.9+/-4.3%). Apoptotic cell death was greater in OSCC (1.6+/-0.6%) than in OM (0.6+/-0.2%, P<0.05) and was most pronounced in the central part of WD OSCC (2.3+/-0.5%). Our results show that Fas is expressed in low quantities in OSCC and that FasL expression correlates negatively with degree of differentiation and apoptosis in OSCC.

Expression of biomarkers (p53, transforming growth factor alpha, epidermal growth factor receptor, c-erbB-2/neu and the proliferative cell nuclear antigen) in oropharyngeal squamous cell carcinomas.

Using immunohistochemistry, expression of p53, transforming growth factor-alpha (TGF-alpha), epidermal growth factor receptor (EGFR), c-erbB-2/neu and proliferating cell nuclear antigen (PCNA) was examined in 26 fresh frozen tissue specimens of oropharyngeal squamous cell carcinomas (SCCs). p53 gene mutations were examined by polymerase chain reaction (PCR)/DNA sequencing methods in 22 carcinomas. The findings were examined for correlations with patients' clinicopathological parameters. Expressions of p53 and PCNA were also examined in 21 formalin-fixed corresponding tissues. Of the fresh frozen tissue specimens, 77% (20/26) showed expression and 68% (15/22) showed mutations (substitutions) of the p53, with significant clustering of the mutations in exons 5 (8/22; 36%), 7 (4/22; 18%) and 8 (5/22; 23%). No mutations were found in exon 6. There was a discordance between expression of p53 protein and mutations of the gene. Parallel to expression and mutations of the p53 found in most of the specimens, expression of TGF-alpha, EGFR, c-erbB-2/neu and PCNA was found in 88% (22/25), 92% (23/25), 58% (14/24) and 91% (21/23) of the specimens, respectively. For the formalin-fixed tissue specimens, 62% (13/21) and 90% (19/21) expressed p53 and PCNA, respectively. Examining for correlations with patients' clinicopathological parameters, expression of p53, TGF-alpha, EGFR and c-erB-2/neu seemed to negatively correlate with the increase of the tumour grade. The present work suggests that: (1) lack of negative growth regulation due to inactivation of the p53 gene together with activation of other proto-oncogenes are necessary genetic events in the carcinogenesis of oropharyngeal SCCs; (2) in oropharyngeal SCCs, p53 gene mutations were clustered in exons 5 (codons 130-186), 7 (codons 230-248) and 8 (codons 271-282) which perhaps suggests that tobacco carcinogens probably affect the mutational hot spots of the p53 gene at codons 157, 175, 186, 248, 273 and 282; and (3) fresh frozen and formalin-fixed tissue specimens give similar results when an immunohistochemical method is applied. The importance of p53, TGF-alpha, EGFR, c-erbB-2/neu and PCNA as biomarkers in oropharyngeal SCCs deserves particular attention because it might offer further understanding of the development of these carcinomas.

The physiologic reservoir of Epstein-Barr virus does not map to upper aerodigestive tissues.

The human Epstein-Barr herpesvirus (EBV) has distinct oncogenic potential, but with over 90% of the adult world population infected, malignancy is a rare outcome of carrier status. However, EBV's association with over half of Hodgkin's and non-Hodgkin's lymphomas as well as several solid tumors, notably nasopharyngeal carcinoma, makes EBV-linked malignancies one of the largest single cancer entities. EBV is a B-lymphotropic virus, well controlled by surveillant T cells in immunocompetent hosts. To determine the presence and site of principal virus reservoirs is a likely prerequisite for understanding the etiology of EBV-associated tumors. Its near 100% association with nasopharyngeal carcinoma led to postulates that the upper aerodigestive tract tissue may be common sites of persistent latent or low-grade replicating infection. Using a protocol designed to avoid viral crosscontamination, the authors employed polymerase chain reaction to detect genomic EBV DNA sequences in 231 biopsies from different mucosal sites in the upper aerodigestive tract, as well as from salivary gland tissue and neck nodes in individuals not suspected to have EBV-related malignancy. Only two samples, one from oral cavity mucosa and one from parotid gland tissue, were positive for EBV. The observation that oropharyngeal tissue is not the principal EBV reservoir has mechanistic implications for the development of EBV-positive tumors in that locale.

Expression of c-erbB proto-oncogene family members in squamous cell carcinoma of the head and neck.

The exact role of oncogenes and proto-oncogenes in the development of squamous cell carcinoma of the head and neck (SCCHN) is still debatable. The expression of the c-erbB-2, c-erbB-3 and c-erbB-4 members of the epidermal growth factor receptor family was examined in 16 fresh frozen tissue specimens of SCCHN using avidin-biotin complex immunohistochemistry, with monoclonal and/or polyclonal antibodies directed against each. Eight fresh frozen tissue specimens of normal oral mucosa were included as controls. Of the SCCHN examined, mixed membrane/cytoplasmic staining (moderate to intense) of c-erbB-2 was found in 14/16 cases (88%). When present in the specimen, immunopositive staining of c-erbB-2 was seen in some of the oral surface epithelial cell layers (basal, intermediate and/or superficial) as well as the tumour islands. Weak cytoplasmic staining of c-erbB-3 and c-erbB-4 was found in 13/16 (81%) and 11/16 (69%) cases respectively. When present in the specimen, c-erbB-3 and cerbB-4 immunopositive staining was seen in some of the oral surface epithelial cell layers (basal, intermediate and/or superficial) as well as the tumour islands. For the positive carcinomas for c-erbB-2, c-erbB-3 and c-erbB-4, the epithelium located near the carcinomas showed weak mixed membrane/cytoplasmic staining of c-erbB-2 in 5/14 cases (36%), weak cytoplasmic staining of c-erbB-3 in 7/13 cases (54%) and of c-erbB-4 in 3/11 cases (27%). All the normal control oral mucosa showed the same pattern of staining for c-erbB-2, c-erbB-3 and c-erbB-4 found in the epithelium located near the carcinomas. Only expression of c-erbB-2 was found to correlate with the increase in the tumour stage, while co-expression of c-erbB-2, c-erbB-3 and c-erbB-4 was found to correlate with the patient survival time in 25% of the carcinomas examined. The present study shows that a) expression of c-erbB-2, but not c-erbB-3 and c-erbB-4 correlates with the increase of the tumour stage b) co-expression of c-erbB-2, c-erbB-3 and c-erbB4 correlates with decreased survival time in some of the cases of SCCHN, but not the majority c) co-expression of the c-erbB family in normal oral mucosa as well as in the carcinoma may question whether the increased tendency for development of the disease is due to co-expression of c-erbB proto-oncogenes in head and neck lesions.

Transcervico-mandibulo-palatal approach for surgical salvage of recurrent nasopharyngeal cancer.

BACKGROUND: Local relapse of nasopharyngeal carcinoma is a difficult problem of management that is usually treated by re-irradiation. Surgical salvage is rarely offered, judging by the paucity of reports in the literature. METHODS: This article reviews the six previously described methods of performing nasopharyngectomy and recounts experience with a series of seven patients using a transcervico-mandibulo-palatal approach, which is described. RESULTS: The results of this small series show survivorship and morbidity which seem to compare favorably with other published surgical treatment options. CONCLUSIONS: If retreatment with radiotherapy is not favored, the transcervico-mandibulo-palatal approach may be a suitable method of surgical salvage for small, locally recurrent, nasopharyngeal cancer.

Papillary thyroid carcinoma metastasizing to the sphenoid-ethmoid sinuses and skull base.

Metastatic papillary carcinoma to the sinuses and skull base is a rare occurrence. A case report of aggressive papillary carcinoma is reported. The tumor contained areas of insular and anaplastic degeneration with strong positive staining for p53 oncogene. Management included primary surgery, administration of radioactive iodine, and external beam radiation.

Analysis of T-cell receptor expressing lymphocytes infiltrating squamous cell carcinomas of the upper aerodigestive tract.

T-lymphocytes expressing T-cell receptors (TCRs) of the gamma/delta type have been suggested to play an important role in mucosal defense against infection and neoplastic transformation. In this study, an immunohistochemical investigation was performed on the distribution of alpha/beta and gamma/delta TCRs among tumor-infiltrating lymphocytes. Thirteen patients with squamous cell carcinomas of the upper aerodigestive tract were studied, using monoclonal antibodies and an avidin-biotin-peroxidase technique. Most of the T-cells had an alpha/beta TCR. Only 1.6% of the T-cells within the cancer tissue and 1.2% of the T-cells in the parenchyma adjacent to the cancer tissue expressed gamma/delta TCRs. These results are consistent with the results of similar studies in bronchial and breast carcinomas. Biopsies from normal oral mucosa in nine healthy individuals showed that 1.3% of the T-cells within the epithelium and 1.0% of those in the lamina propria adjacent to the epithelium expressed gamma/delta TCRs. Quantitatively the results do not support the theory that gamma/delta T-cells play an important role in the immunological response against cancer tissue in the mucosa of the upper aerodigestive tract. The functional role of these cells in the mucosa and in response to carcinomas is, however, still uncertain.

[Epipharyngeal cancer]. / Epifarynxcancer.

The article surveys the incidence and pathogenetic factors of nasopharyngeal carcinoma. The authors present a retrospective study of 36 patients with malignant tumors in the nasopharynx who were treated at Haukeland University Hospital between 1972 and 87. 26 out of 27 patients with nasopharyngeal carcinoma had advanced disease. Symptoms and signs are described. Radiation therapy was the main treatment modality. The total five year survival was 18%.

Granulomatos cervical lymphadenitis.

One hundred and thirty-nine cases of pathologically involved cervical lymph nodes have been reviewed, and granulomatous lymphadenitis found in 29 patients (20.9 per cent). There were two cases of sarcoidosis, 10 of tularemia, five patients (3.6 per cent) had tuberculous lymphadenitis and 12 (8.7 per cent) fulfilled commonly accepted criteria for infection with atypical mycobacteria. The clinical features of the latter condition, which is probably insufficiently recognized, are reviewed, and surgery is recommended as the primary treatment modality.