Long-term subjective tongue function after partial glossectomy.

There have been limited studies of subjective tongue function over long-term follow-up in spite of swallowing and articulation disorders are common complications of glossectomy. To assess long-term subjective swallowing and articulation function after partial glossectomy. A total of 63 patients with the mobile tongue cancer who underwent partial glossectomy without reconstruction were interviewed to score their swallowing and articulation function on a 100-point scale. The relation of this subjective scoring to the perioperative data was subjected to multivariate analysis. The mean patient age was 53·4 (19-81) years, and the mean follow-up duration was 78·9 (14-277) months. Mean swallowing and articulation function score was 87·7 ± 6·1 and 88·6 ± 5·4. Age, follow-up duration, T stage and resection volume were significantly correlated with swallowing function (P = 0·026, 0·029, 0·016, 0·002, respectively); follow-up duration was correlated with articulation function (P = 0·039). Patients who undergo partial glossectomy without reconstruction generally demonstrate good function on long-term follow-up. Subjective dysfunction was correlated with larger resection volume, older age and shorter follow-up duration.

Class III beta-tubulin, but not ERCC1, is a strong predictive and prognostic marker in locally advanced head and neck squamous cell carcinoma.

BACKGROUND: Recent researches revealed that class III beta-tubulin (TUBB3) is a prognostic marker in various tumors and role of TUBB3 in head and neck squamous cell carcinoma (HNSCC) is not defined yet. We analyzed the significance of TUBB3 expression along with p53 and ERCC1 in locally advanced HNSCC patients receiving cisplatin-based induction chemotherapy. MATERIALS AND METHODS: Retrospective review of medical records at Seoul National University Hospital between 1998 and 2007 was carried out. Immunohistochemical stain of TUBB3, p53, and ERCC1 was done in paraffin-embedded tumor tissue. We assessed response to treatment, progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS). RESULTS: Eighty-five patients with oropharyngeal, hypopharyngeal, and laryngeal cancers received induction chemotherapy with 5-fluorouracil (5-FU) and cisplatin (n = 55), or 5-FU, cisplatin, and docetaxel (Taxotere) (n = 30). Eighty-three received definitive treatment after induction chemotherapy, where 62 received radiotherapy and 21 received surgery. TUBB3-positive patients showed lower response rate than TUBB3-negative patients (69% versus 88%, P = 0.039). Shorter median PFS was observed in TUBB3-positive group (12 versus 47 months, P = 0.001). Shorter median OS was observed in TUBB-positive group not reaching statistical significance (30 versus 59 months, P = 0.072). TUBB3 status significantly influenced CSS (35 months versus not reached, P = 0.017). Positive p53 status was related to poorer OS and CSS. ERCC1 showed no influence on chemotherapy response, PFS, OS, and CSS. CONCLUSION: TUBB3 is a predictive and prognostic marker along with well-known p53 in HNSCC patients receiving cisplatin-based induction chemotherapy. Clinical impact of ERCC1 is not evident in this setting.

Validity and reliability of the Korean version of the Speech Handicap Index in patients with oral cavity cancer.

The aims of this study were to evaluate the cross-cultural adaptation of the Speech Handicap Index (SHI) for Korean subjects and to determine its reliability and utility in patients with oral cavity cancer. The Korean version of the SHI was administered to 50 healthy subjects and 56 patients with speech problems resulting from treatment for oral cavity cancers. The content and construct validity, internal consistency, and test-retest reliability were examined. Healthy subject and patient group scores were compared, and the Mann-Whitney U-test was used to determine discriminatory ability. The Korean version of the SHI had high internal consistency (Cronbach's alpha=0.99) and test-retest reliability for the total and subscales: total (T) 0.98, speech (S) 0.99, and psychosocial (P) 0.97. Mean scores in the healthy group were 0.5 (T), 0.2 (S), and 0.2 (P), whereas those in the patient group were 34.3 (T), 16.6 (S), and 15.5 (P). The scores differed significantly between the groups (P<0.05). The Korean version of the SHI can be a useful tool to evaluate a patient's self-perception of their speech dysfunction in daily life and to better understand postoperative speech disorders in patients with oral cavity cancer.

Human tumor antigen-specific T lymphocytes and interleukin-2-activated natural killer cells: comparisons of antitumor effects in vitro and in vivo.

Human antitumor effector cells include class I major histocompatibility complex (MHC)-restricted T cells and non-MHC-restricted natural killer (NK) cells. These two types of effector cells have not been directly compared for the ability to eliminate tumor cell targets. Here, we compare in vitro and in vivo antitumor functions of two human T-cell lines specific for a shared tumor antigen to the antitumor functions of A-NK cells, a subset of IL-2-activated NK cells. Human squamous cell carcinoma of the head and neck cell lines cultured in suspensions or as spheroids or tumor xenografts established in nude mice were used to evaluate antitumor functions of IL-2-activated and expanded T and NK effector cells in various assays, both in vitro and in vivo. Both tumor cell targets, PCI-13 and OSC-19, expressed class I and II MHC antigens after IFN-gamma pretreatment, gave rise to tumors upon injection into immunosuppressed nude mice, and were resistant to lysis by resting NK cells but sensitive to lysis mediated by A-NK cells or HLA-A2-restricted T-cell lines specific for a shared squamous cell carcinoma of the head and neck antigen. No significant differences were observed in the ability of A-NK cells or tumor-specific T cells to bind to tumor cell monolayers or to enter into spheroids. However, A-NK cells mediated significantly higher killing than tumor-specific CD8+ T cells in 4-h 51Cr-release assays (a measure of cell membrane damage and necrosis), 1-h [3H]thymidine-release assays (a measure of DNA fragmentation and apoptosis), and in terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays (a measure of apoptosis). In contrast, CD8+ T cells were consistently more effective than A-NK cells in inducing growth inhibition of tumor cells in 24-h MTT assays. In the presence of tumor-specific antibodies, A-NK cell binding, entry into spheroids, and infiltration into tumor in vivo were significantly increased. In vivo perilesional delivery of effector cells to mice with established tumors indicated that human A-NK cells exert antitumor effects as potent as those of tumor-specific T cells. However, in contrast to tumor-specific T cells, A-NK cells are readily available for cancer therapy, expand rapidly in culture without prior sensitization, and can be armed with antitumor antibodies to increase localization of effector cells to the tumor.

Locoregional response and increased natural killer activity after intratumoral injection of HLA-B7/beta2-microglobulin gene in patients with cancer.

The purpose of this study was to assess the therapeutic potential of injecting the gene for HLA-B7/beta2-microglobulin into the subcutaneous metastatic nodules of patients who are refractory to conventional treatments. The nine patients evaluated were divided into three groups and given escalating doses of DNA (20, 40, and 100 microg of the HLA-B7 plasmid DNA/lipid complex for each group) every 2 weeks. Biopsy specimens from the treated tumor nodules of all nine patients were positive for the presence of DNA and for HLA-B7 mRNA expression. Moreover, in six of the nine patients, immunohistology of tumor biopsy samples revealed the expression of recombinant HLA-B7 protein. Also, all nine patients showed an increase in NK activity in their circulating peripheral blood lymphocytes. In two lung cancer patients, one partial and one mixed response was observed after gene transfer. These responses were confined to the treated nodules and the untreated locoregional lymph nodes; the lung masses showed no regression. Remission durations were 14 and 6 weeks, respectively, and in a total of 35 cycles no significant toxicities were observed. Immunohistologic analysis revealed an increased infiltration of CD4+ T cells, macrophages, and NK cells after therapy. In two responding cases, direct intratumoral injection of an allogeneic class I gene could elicit an antitumor response in locoregional areas, possibly through the activation of NK cells.

Enhancement of adenoviral transduction with polycationic liposomes in vivo.

Although the high transfection efficiency with adenovirus in vitro is well documented, it is still not clear whether adenoviral vectors are effective in vivo in solid tumor models. In our preliminary experiment, transduction of tumor tissue was limited to just around the injection site after intratumoral injection of the adenoviral vector. To improve the transduction efficiency in vivo, we tried a combination of adenoviral vector and liposome in our animal model. Adenovirus carrying human placental alkaline phosphatase (AdALP) and Lipofectamine or 1,3-di-oleoyloxy-2-(6-carboxyspermyl)-propylamide were used as a marker gene and the cationic liposome, respectively. A >15-fold increase in the transfection efficiency was observed in CT26 tumor cell lines with the combination of AdALP adenovirus carrying murine granulocyte-macrophage colony-stimulating factor (AdmGM-CSF), and liposome compared with adenovirus alone, showing the feasibility of the combination treatment. In the animal model, with the combination of liposome and AdALP, deeper and wider distribution of the marker gene in the tumor mass was shown. We conclude that the limitations of direct application of adenoviral vectors in a solid tumor model could be overcome by the use of cationic liposomes. This approach will facilitate the more effective delivery of adenoviral vectors in a clinical trial setting.

Neoadjuvant chemotherapy and radiation therapy compared with radiation therapy alone in advanced nasopharyngeal carcinoma.

PURPOSE: To analyze the impact of neoadjuvant chemotherapy on the treatment of locoregionally advanced nasopharyngeal carcinoma and to assess the outcomes of patients receiving such treatment. METHODS AND MATERIALS: We analyzed 137 previously untreated and histologically confirmed advanced stage nasopharyngeal carcinoma patients treated with either radiation therapy only or combined radiation therapy and chemotherapy at the Seoul National University Hospital between 1984 and 1996. The stage distribution was as follows: AJCC Stage III-21, Stage IV-61 in the radiation therapy group (RT group); AJCC Stage III-1, Stage IV-54 in neoadjuvant chemotherapy and radiation therapy group (CT/RT group). The median follow-up for surviving patients was 48 months. RESULTS: The 5-year overall survival (OS) rates were 71% for the CT/RT group and 59% for the RT group (p = 0.04). The 5-year actuarial disease-free survival (DFS) rates were 63% for the CT/RT group and 52% for the RT group (p = 0.04). Distant metastasis (DM) incidence was significantly lower in the CT/RT group. The 5-year freedom from distant metastasis rates were 84% for the CT/RT group and 66% for the RT group (p = 0.01). The incidence of locoregional failures was also lower in the CT/RT group, although this difference did not reach statistical significance (69% vs. 56%, p = 0.09) CONCLUSION: While not providing conclusive evidence, historical evidence from this institution suggests that neoadjuvant chemotherapy significantly improves both overall and the disease-free survival of patients with advanced stage nasopharyngeal carcinoma.

Reconstruction of human hard-palate mucosal epithelium on de-epidermized dermis.

Artificial hard-palate mucosa equivalents were reconstructed using keratinocytes derived from normal human hard-palate and de-epidermized dermis. Reconstructed hard-palate mucosal epithelium formed in three-dimensional culture was compared to native hard-palate mucosal epithelium and reconstructed oral buccal mucosal epithelium with regard to keratin expression. Artificial hard-palate mucosal epithelium reconstructed in medium with delipidized serum showed a differentiation pattern similar to that of hard-palate epithelium in vivo. The present study also confirmed that keratinocytes derived from hard-palate mucosa are intrinsically different from those of nonkeratinizing oral surfaces.

A rational approach to the use of hepatic transplantation in the treatment of metastatic neuroendocrine tumors.

BACKGROUND: Gastrointestinal neuroendocrine tumors are slow growing, and metastases are often limited to the liver. Whereas in asymptomatic patients, observation alone may be reasonable, in patients with neuroendocrine tumors and unresectable hepatic metastases, transplantation of the liver may be beneficial. We have developed a protocol in which patients with multiple hepatic metastases are initially treated with chemotherapy and embolization to control symptoms and inhibit tumor growth. Hepatic transplantation is reserved for patients in whom tumor progresses or symptoms of hormone production or mass effect persist. STUDY DESIGN: This is a retrospective review of eight patients with neuroendocrine tumor metastases who were referred to the Mount Sinai Hospital for evaluation for hepatic transplantation. RESULTS: Of the eight patients, three have undergone transplantation; all are alive, with no evidence of tumor recurrence at 12 to 30 months. In two patients, symptoms have been controlled by embolization of the hepatic artery or chemotherapy, or both; another has had massive hepatomegaly as a result of tumor progression, with wasting and portal hypertension, and currently awaits transplantation. Two patients died as a result of progressive disease, soon after referral. CONCLUSION: Transplantation of the liver may be an important treatment modality for a selected group of patients with neuroendocrine tumors unresponsive to conventional therapy.

Congenital fistula from ectopic accessory parotid gland: diagnosis with CT sialography and CT fistulography.

We report a case of congenital fistula from ectopic accessory parotid gland to the cheek demonstrated by CT sialography and CT fistulography. The right parotid gland was abnormally located lateral to masseter muscle. The fistula was arising from an ectopic accessory parotid gland with ectopic duct positioned anterior to masseter muscle. CT sialography and CT fistulography were very helpful in the diagnosis and surgical planning.

The effect of prostaglandin and its inhibitor on antibody-dependent cellular cytotoxicity against human squamous cell carcinoma of head and neck.

The effects of chimeric monoclonal antibodies (cMAbs), prostaglandin E2(PGE2), and indomethacin (INDO) on antibody-dependent cellular cytotoxicity (ADCC) against human squamous cell carcinoma of head and neck (SCCHN) cell line were examined. Using the PCI-50 SCCHN cell line as target and normal human peripheral blood mononuclear cells as the effector, ADCC was enhanced by the treatment of cMAbs (1.25 micrograms/ml), but was inhibited by exogenous PGE2(5 x 10-7M). The effects of cMAb and PGE2 were dose-dependent. Maximal suppression of activity occurred when PGE2 was present during the entire 4 hour 51Cr-release assay period, whereas pretreatment of effector cells with PGE2 had minimal inhibitory effect after washing. These results indicate that decreased ADCC seen with SCCHN targets treated with PGE2 is related to post-binding events, such as binding of effector and target cells. Pre-treatment of effector cells with INDO (1 microgram/ml) resulted in restoration of NK activity which was inhibited by PGE2. Our in vitro results suggest that INDO can increase tumor cell killing by the reversal of the suppression for many immune functions by PGE2.

Effect of GM-CSF and IL-2 co-expression on the anti-tumor immune response.

We evaluated the effect of potential therapeutic genes, GM-CSF and IL-2 respectively, or in combination of both cytokines, on the activation of systemic antitumor responses. CT26 tumor cells were modified to secrete GM-CSF and/or IL-2. The growth rate of the modified tumor cells versus the parental CT26 cells did not show any difference. When we implanted the CT26 tumor cells which secrete either GM-CSF or IL-2, delayed and suppressed tumorigenicity was observed. However, another CT26 cell line which expresses both GM-CSF and IL-2 (CT26/GMCSF/IL-2) did not form any tumor mass in the immunocompetent syngeneic Balb/c mice, showing the potential immune responses. Immunohistochemical examination of the modified tumor masses implanted with the cells expressing GM-CSF or IL-2 showed increased necrosis and infiltration of NK (CD56+) lineage cells and macrophage/monocytes. In the vaccination model, the growth of rechallenged wild-type CT26 was more suppressed int he mice which were injected with GM-CSF or IL-2, however, the wild-type CT26 tumor formed normal tumor mass in the mice vaccinated with CT26/GM-CSF/IL-2 showing acute non-T-cell mediated immune response. As a treatment, we injected those modified tumor cells into the established tumor. There we could find tumor growth suppression by the injection of cytokine-modified CT26 cells, especially by the CT26/GM-CSF/IL-2. In the present study we could induce the eradication of tumorigenicity by the transfection of both GM-CSF and IL-2 genes and a potent role in the growth suppression of an established tumor.

Cationic liposome-enhanced adenoviral gene transfer in a murine head and neck cancer model.

The effect of combining adenoviral vector and cationic liposomes on the efficiency of gene transfer to head and neck tumor cells was investigated. Two human and two murine cell lines were used for the screening of gene transfer efficiency using an adenoviral vector. Cationic liposome-enhanced gene transfer was checked using a murine squamous carcinoma cell line, SCCVII/SF. A considerable difference in the efficiency of gene transduction was observed among the cell lines. The combination of DOSPER and adenoviral vector containing human alkaline phosphatase showed a remarkable enhancing effect in gene transfer in vitro and in vivo, compared to the adenovirus alone or control groups. With an improvement in the efficiency of gene transfer, it may be possible not only to enhance the expression of transduced genes, but also to deliver a smaller amount of virus, as a result, reducing toxicity and the immune response against adenovirus.

Human oral buccal mucosa reconstructed on dermal substrates: a model for oral epithelial differentiation.

To develop a model for the study of oral epithelial differentiation, we reconstructed artificial buccal mucosa equivalents using keratinocytes and fibroblasts or de-epidermized dermis derived from non-cornifying buccal mucosa. The buccal mucosa equivalents reconstructed in this way showed a morphology closely mimicking that of their in vivo counterparts. There was no formation of horny layers and granular layers. The expression of various differentiation markers such as K13, involucrin and loricrin was consistent with that of the in vivo state, and indicative of the hyperproliferative state. We also demonstrated that the differentiation of oral epithelial cells was influenced by the de-epidermized dermis and subepithelial fibroblasts. The epidermis of buccal mucosa equivalents seemed to be less sensitive to retinoic acid than that of the skin. The effects of calcipotriol on the buccal mucosa equivalent and the skin epidermis were different. These results suggest that the pharmacological effects of retinoic acid and calcipotriol on the buccal mucosa are different from those on the skin. A useful model system for studies of oral keratinocyte differentiation and pharmacological research could be based on these artificial buccal mucosa equivalents.

Fibrosing inflammatory pseudotumors of the central skull base.

The most important step in the differential diagnosis of mass lesions of the central skull base is to rule out malignant neoplasms. However, nonneoplastic lesions, such as infections or nonspecific inflammatory lesions of the skull base, can mimic malignant processes. In this study, the authors analyzed seven cases of nonneoplastic noninfectious mass-forming lesions involving the central skull base. In most cases, malignant processes were suspected at the initial phase of diagnostic work-up, but subsequent histologic examinations revealed that these lesions consisted of inflammatory cells and fibrosis without neoplastic cells. Common manifestations were pain and other neurological symptoms related to the involved anatomical sites. A variety of neurological dysfunctions of the cranial nerves not including the olfactory and spinal accessory nerves were observed. No patient developed separate lesions outside the head and neck region. After the pathologic diagnosis, most of the patients were treated with oral steroid therapy, with initial doses of prednisolone, 60 to 100 mg/d. It was difficult to relate responsiveness to steroid therapy with the histologic degree of sclerosis, fibrosis, or chronicity of the disease in these cases. Otolaryngologists should be aware of this disease when making treatment decisions for their patients with skull base lesions.

Effects of phenylephrine on ciliary beat in human nasal respiratory epithelium: quantitative measurement by video-computerized analysis.

The in vitro effects of phenylephrine solution on ciliary beat frequency (CBF) in terms of different concentrations and exposure times were investigated using a video-computerized analysis technique. Nasal epithelial cells were taken from inferior turbinate of 10 volunteers by scraping the nasal mucosa with a cytology brush. CBF was measured in five different concentrations including 0.125%, 0.25%, 0.5%, 1%, and 2.5%. Each specimen was incubated in different solution for 6 days and CBF was measured at 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 days, and 6 days. CBF decreased significantly after 12-hour incubation in 0.125% phenylephrine solution and after 8-hour incubation in 0.25% phenylephrine solution, both clinically used concentrations. There were significant decreases in CBF after incubation in 0.5% phenylephrine for 2 hours, in 1% for 1 hour, and in 2.5% for 30 minutes (P < 0.05, repeated measure analysis of variance [ANOVA]). CBF of the nasal respiratory ciliated cells significantly decreased with increasing concentrations of phenylephrine solution and with increasing incubation times at the same concentration (P < 0.05, repeated measure ANOVA). The results of this study suggest that phenylephrine may inhibit ciliary beat in vitro by its pharmacological effect at lower concentrations than clinically used ones.

Establishment and characterization of human laryngeal squamous cell carcinoma cell lines.

OBJECTIVES: Six human laryngeal squamous cell carcinoma cell lines (SNU-46, -585, -899, -1066, -1076, -1214) established from Korean patients are reported. STUDY DESIGN: In vitro culture of six squamous cell carcinoma cell lines derived from primary tumors of the larynx. Description of the cell line phenotypes and determination of molecular characteristics. METHODS: Six laryngeal squamous cell carcinoma cell lines were cultured. The cell phenotypes, including the histopathology of the primary tumors and in vitro growth characteristics, were determined. Molecular characterization was also performed, including DNA fingerprinting analysis and abnormalities of p15, p16, p53, and TGF-betaRII genes by polymerase chain reaction-based single strand conformation polymorphism and sequencing analysis. RESULTS: All cell lines grew as adherent cells; five lines grew as monolayers and one other line grew as stratifying colonies. All lines showed 1) high viability (75%-92%) with various doubling times (36-96 h); 2) absence of Mycoplasma and other bacteria; and 3) genetic heterogeneity by DNA profile analysis. p53 Mutations were found in three lines and p16 mutations were observed in five cell lines. TGF-betaRII mutations were found in two lines: one line had frameshift mutation and another line had a missense mutation at the kinase domain. CONCLUSIONS: These newly established and characterized laryngeal squamous cell carcinoma cell lines will be useful for investigating the biologic characteristics of laryngeal cancer.

Sclerotherapy with picibanil (OK-432) for congenital lymphatic malformation in the head and neck.

HYPOTHESIS/OBJECTIVES: Congenital lymphatic malformations of the head and neck (LMHN) present special challenges to the otolaryngologist-head and neck surgeon. Recently, a number of sclerotherapy trials have shown promising results. In this study, we present our experiences with picibanil (OK-432) sclerotherapy for this lesion. STUDY DESIGN: Retrospectively review. METHODS: We retrospectively reviewed 21 patients who have undergone sclerotherapy with picibanil for LMHN. RESULTS: Satisfactory response with complete or nearly complete shrinkage of the lesions was observed in 15 cases after repeated sclerotherapy (average, two times). We did not observe any significant morbidity or complications in the patients treated with picibanil. Reduction in size of the mass was achieved in weeks to months. Some of the patients who had not had any other previous treatment showed remarkable reductions in size even after the first therapy. When we used picibanil sclerotherapy as a primary treatment for the LMHN, most of our patients showed satisfactory results regardless of the size or location of the lesions. CONCLUSION: Given with our experience and the reports that failure of picibanil sclerotherapy does not hinder subsequent surgical salvage procedures, we recommend trying picibanil sclerotherapy as a primary treatment for the LMHN and performing surgical excision as a secondary modality if the response to the sclerotherapy is not satisfactory.

Traumatic pseudoaneurysm of the intracavernous ICA presenting with massive epistaxis: imaging diagnosis and endovascular treatment.

Traumatic pseudoaneurysm of the intracavernous internal carotid artery (ICA) is a very rare cause of epistaxis but is a life-threatening clinical situation when left untreated. The authors have experienced four cases of traumatic pseudoaneurysm involving the intracavernous ICA. Delayed massive epistaxes developed 1 to 8 months after trauma and initial transient epistaxis in all four patients. Three of the cases were successfully managed by the detachable balloon occlusion (DBO) of the ICA along with the aneurysm openings. In one case, a large pseudoaneurysm destroying a large area of the central skull base with peripheral blood clot was demonstrated on computed tomography, magnetic resonance imaging, and angiography; this patient died due to massive epistaxis before the trial of DBO. Imaging findings of pseudoaneurysms involving the intracavernous ICA in the four cases are described, and the role of endovascular treatment is discussed.

Videostrobokymography: a new method for the quantitative analysis of vocal fold vibration.

OBJECTIVES: To develop a new analysis method for the quantitative assessment of vibration of the vocal folds, using conventional videostroboscopic image data. METHODS: We used prerecorded videostroboscopic images to evaluate quantitatively the vibration of the vocal folds. Successive images were converted as digital images by means of an image-grabbing board, processed for analysis, and reconstructed as kymograms by rearranging the same lines of all processed images along the time axis. RESULTS: We developed a new technique for evaluating the vibration of the vocal folds. The vibrations of multiple vocal fold regions were easily and objectively evaluated by this technique. The objective parameters, such as open quotient and asymmetry index, could be obtained easily using this technique. CONCLUSIONS: Videostrobokymography demonstrated objectively the vibrations of several vocal fold regions at the same time. This technique has the potential to be a new tool to analyze and monitor the pathological changes and treatment results of vocal fold movement in a more refined quantitative fashion, using videostroboscopic images.