[Corrigendum] Antitumor effects of IDN5109 on head and neck squamous cell carcinoma.

Oncol Rep 15: [Related article:] 329­334, 2006; DOI: 10.3892/or.15.2.329 After the publication of the article, the authors noted that the relevance of the findings reported in this article on IDN5109 inhibition of growth of head and neck squamous cell carcinoma (HNSCC) is now in question. To examine the antitumor effect of IDN5109, this study was conducted using YCU-H891 and KCC-MS871 cell lines that the authors believed to be HNSCC cell lines. Because different human leukocyte antigen (HLA) was detected in 2 cell lines (KCC-TCM901 and KCC-T873) which were derived from the same patient in an experiment after publication, 16 cell lines established in our institution were analyzed by short tandem repeat (STR) analysis. STR analysis revealed that genotype of KCC-TCM901, YCU-H891 and KCC-MS871 was identical to that of HeLa cells, and that genotype of YCU-T891 was identical to that of YCU-L891, which was considered to be cross-contamination.

[Corrigendum] Antitumor effects of ZD6474 on head and neck squamous cell carcinoma.

Oncol Rep 17: [Related article:] 289­295, 2007; DOI: 10.3892/or.17.2.289 After the publication of the article, the authors noted that the relevance of the findings reported in this article on ZD6474 inhibition of growth of head and neck squamous cell carcinoma (HNSCC) is now in question. To examine the antitumor effect of ZD6474 in vitro and in vivo, this study was conducted using YCU-H891 cell line that the authors believed to be HNSCC cell line. Because different human leukocyte antigen (HLA) was detected in 2 cell lines (KCC-TCM901 and KCC-T873) which were derived from the same patient in an experiment after publication, 16 cell lines established in our institution were analyzed by short tandem repeat (STR) analysis. STR analysis revealed that genotype of KCC-TCM901, YCU-H891 and KCC-MS871 was identical to that of HeLa cells, and that genotype of YCU-T891 was identical to that of YCU-L891, which was considered to be cross-contamination.

Combined molecular targeted drug therapy for EGFR and HER-2 in head and neck squamous cell carcinoma cell lines.

The epidermal growth factor receptor (EGFR) and related family member, HER-2, are often overexpressed simultaneously in patients with a variety of malignant tumors, and the combination may cooperatively promote cancer cell growth and survival. The purpose of this study was to examine antitumor effects of the combination treatment of cetuximab and trastuzumab on head and neck squamous cell carcinoma (HNSCC) using 16 HNSCC cell lines in terms of antiproliferative effect and antibody-dependent cell-mediated-cytotoxicity (ADCC). Previously we have reported the expression levels of EGFR mRNA on 16 HNSCC cell lines. All cell lines expressed mRNA for EGFR, HER-2 and HER-3; 12 cell lines expressed mRNA for HER-4; and 4 cell lines did not express mRNA for HER-4. In in vitro proliferation assay, the combination treatment of cetuximab and trastuzumab significantly lowered cell viability compared to either drug alone. The mRNA expression levels of EGFR and HER-2 were not correlated with the efficacy of the combination treatment of cetuximab and trastuzumab and the expression levels of HER-3 and HER-4 also showed no correlation with the efficacy of the combination treatment. We evaluated the gene status of HER-2 exons 23 and 24 in 16 HNSCC cell lines, but there was no mutation of HER-2 in any of the cell lines. Either drug showed ADCC in the 3 cell lines using peripheral blood mononuclear cells (PBMCs), however, a significant combination effect was not observed. Combined molecular targeted antibody drug therapy for EGFR and HER-2 may be useful in the treatment of HNSCC.

Comparison of concurrent chemoradiotherapy versus induction chemotherapy followed by radiation in patients with nasopharyngeal carcinoma.

PURPOSE: The study aimed to evaluate the efficacy of concurrent chemoradiotherapy (CCRT) with platinum-based chemotherapy as a primary treatment for nasopharyngeal carcinoma (NPC) and to further compare the results of CCRT with these of neoadjuvant chemotherapy (NAC) followed by radiotherapy (RT). PATIENTS AND METHODS: Before 1998, 21 patients with NPC received NAC followed by RT (NAC-RT). Between 1999 and 2008, a total of 25 NPC patients received CCRT. The CCRT group received a regimen including docetaxel (50 mg/m(2), day1), cisplatin (CDDP, 60 mg/m(2), day4) and continuous 5-fluorouracil (5-FU) infusion (600 mg/m(2), day 1-5), the TPF regimen, or a regimen including CDDP (60 mg/m(2), day4), continuous 5-FU infusion (600 mg/m(2), day 1-5), methotrexate (MTX, 30 mg/m(2), day 1) and leucovorin (LV, 20 mg/m(2), day 1-5), PFML regimen. The CCRT group received 2 cycles of chemotherapy during definitive RT. The NAC group of patients received a PFML regimen. RESULTS: The overall response rate after CCRT was 96%. The 3-year and 5-year disease-specific survival rates were 75.6% and 60.1%, respectively. In patients receiving NAC-RT, the 3-year and 5-year disease-specific survival rates were 84.1% and 67.3%, respectively. There was no difference observed in terms of survival rates between the group receiving CCRT and that receiving NAC-RT. CONCLUSION: CCRT with the TPF or PFML regimen was tolerable, and the NPC patients receiving this treatment showed excellent survival rates. In comparison to the group receiving NAC-RT, CCRT had no advantage in terms of the survival rate. In the future, the control of distant metastasis might play an important role in improving the survival rate of patients with advanced NPC receiving CCRT.

Acoustic characteristics of ataxic speech in Japanese patients with spinocerebellar degeneration (SCD).

BACKGROUND: In English- and German-speaking countries, ataxic speech is often described as showing scanning based on acoustic impressions. Although the term 'scanning' is generally considered to represent abnormal speech features including prosodic excess or insufficiency, any precise acoustic analysis of ataxic speech has not been performed in Japanese-speaking patients. This raises the question of what is the most dominant acoustic characteristic of ataxic speech in Japanese subjects, particularly related to the perceptual impression of 'scanning'. AIMS: The study was designed to investigate the nature of speech characteristics of Japanese ataxic subjects, particularly 'scanning', by means of acoustic analysis. METHODS & PROCEDURES: The study comprised 20 Japanese cases with spinocerebellar degeneration diagnosed to have a perceptual impression of scanning by neurologists (ataxic group) and 20 age-matched normal healthy subjects (control group). Recordings of speech samples of Japanese test sentences were obtained from each subject. The recorded and digitized acoustic samples were analysed using 'Acoustic Core-8' (Arcadia Inc.). OUTCOMES & RESULTS: Sentence duration was significantly longer in the ataxic group as compared with the control group, indicating that the speaking rate was slower in the ataxic subjects. Segment duration remained consistent in both vowels and consonants in the control group as compared with the ataxic group. In particular, the duration of vowel segments, i.e. the nucleus of Japanese mora, was significantly invariable in the control group regardless of differences between subjects as well as in segments compared with the ataxic group. In addition, the duration of phonemically long Japanese vowels was significantly shorter in the ataxic group. CONCLUSIONS & IMPLICATIONS: The results indicate that the perceptual impression of 'scanning' in Japanese ataxic cases derives mainly from the breakdown of isochrony in terms of difficulty in keeping the length of vowel segments of Japanese invariable during speech production. In addition, the tendency toward irregular shortening of the length of phonemically long Japanese vowels is thought to reinforce the impression of 'scanning' in ataxic speech in Japanese cases.

Diagnostic sensitivity of ¹8fluorodeoxyglucose positron emission tomography for detecting synchronous multiple primary cancers in head and neck cancer patients.

We assessed the sensitivity of positron emission tomography (PET) for detecting synchronous multiple primary cancers, particularly synchronous esophageal cancers in head and neck cancer patients. We retrospectively reviewed 230 head and neck cancer patients. All the patients routinely underwent the following examinations: urinalysis, occult blood, tumor marker detection [squamous cell carcinoma (SCC), cytokeratin fragment (CYFRA), and carcinoembryonic antigen (CEA)], esophagogastroduodenoscopy, colonoscopy (when CEA was high or occult blood was positive), abdominal ultrasonography, plain chest computed tomography (CT), and PET. Bronchoscopy was performed when CT revealed lung shadow of central region. Synchronous multiple primary cancers were detected in 42 (18.2%) patients. The diagnostic sensitivity of PET for synchronous primary cancers was as follows: esophagus, 7.6% (1/13); stomach, 25.0% (2/8); lung, 66.7% (4/6); head and neck, 75.0% (3/4); colon, 0% (0/1); kidney, 0% (0/1); and subcutaneous, 100% (1/1). The sensitivity of PET for detecting synchronous esophageal cancers is low because these are early-stage cancers (almost stage 0-I). Therefore, it is necessary to perform esophagogastroduodenoscopy for detecting synchronous esophageal cancers. PET is an important additional tool for detecting synchronous multiple primary cancers because the diagnostic sensitivity of PET in synchronous head and neck cancer and lung cancer is high. But PET has the limitation of sensitivity for synchronous multiple primary cancers because the diagnostic sensitivity of PET in synchronous esophageal cancer is very low.

Two cases of congenital cholesteatoma of the tympanic membrane.

Congenital cholesteatoma of the tympanic membrane is rare, and lesions without a history of otitis media or any other adverse events involving the tympanic membrane are extremely rare. We report two cases of this lesion; one was a 3-year-old girl who underwent removal of a cholesteatoma using retroauricular approach and a partial myringoplasty with an underlay technique, and the other was a 2-year-old girl in whom a cholesteatoma was enucleated without grafting. This disease is thought to be of embryonic origin.

Gene status of head and neck squamous cell carcinoma cell lines and cetuximab-mediated biological activities.

Cetuximab is a chimeric IgG1 monoclonal antibody that targets epidermal growth factor receptor (EGFR). Cetuximab binds to EGFR and prevents phosphorylation of EGFR. Moreover, preclinical results have shown the ability of cetuximab to induce either complement-mediated tumor cell killing (CDC) or antibody-dependent cell-mediated-cytotoxicity (ADCC). We previously reported mutation in EGFR regarding head and neck squamous cell carcinoma (HNSCC) cell lines. In the present study, we analyzed the same 16 HNSCC cell lines for mutations in KRAS, PIK3CA, BRAF and PTEN. Furthermore, we evaluated cetuximab-mediated biological activities (antiproliferative effect by the MTT assay and ADCC) regarding these cell lines. Mutations in PIK3CA and PTEN were observed in two cell lines (2/16, 12.5%), but no mutation was observed in KRAS and BRAF. The antiproliferative effect of cetuximab by the MTT assay was not strong, and no correlation was observed between the antiproliferative effect of cetuximab and mutations in EGFR, KRAS, PIK3CA, BRAF and PTEN in these cell lines. Therefore, the mutation status of EGFR and downstream molecules were not useful for predicting the antitumor effects of cetuximab on HNSCC. Cetuximab-mediated ADCC was observed in these cell lines and might have been influenced by the expression of EGFR. Therefore, cetuximab-mediated ADCC seems to be an important part of the antitumor mechanisms of cetuximab and the expression levels of EGFR might influence the antitumor activity of cetuximab. Therefore, besides the antiproliferative effect of cetuximab by the MTT assay, it appeared important to evaluate cetuximab-mediated ADCC as well as EGFR expression in HNSCC cells.

Efficacy of fluoro-2-deoxy-D-glucose positron emission tomography to evaluate responses to concurrent chemoradiotherapy for head and neck squamous cell carcinoma.

OBJECTIVE: This study evaluates the utility of fluorodeoxyglucose-positron emission tomography (FDG-PET) in patients with head and neck squamous cell carcinoma (HNSCC) who received concurrent chemoradiotherapy (CCRT). METHODS: Sixty-five patients were recruited for this study between November 2002 and April 2007. The FDG-PET scan was performed before treatment and 4-6 weeks after treatment. RESULTS: The mean of maximum standardized uptake value (SUVmax) before treatment at the primary tumor site was 8.1 (range, 2-22). The sensitivity of FDG-PET for the diagnosis of primary tumor site was 98%. The mean of SUVmax after treatment was 2.6 (range, 2-5). The sensitivity, specificity, and accuracy of FDG-PET for the diagnosis of primary tumor site after treatment were 100%, 40%, and 46%, respectively. The mean of SUVmax before treatment at the nodal site was 4.7 (range, 2-16). The mean of SUVmax after treatment was 2.0 (range, 2-6.7). The pre-treatment SUVmax of T2, T3, and T4 stages were significantly higher than that of the T1 stage. The N stage had no correlation in terms of the pre-treatment nodal site SUVmax. CONCLUSION: Our results indicate that FDG-PET is a useful imaging method for evaluating the response of CCRT in patients with HNSCC. However, performing FDG-PET 4-6 weeks after treatment may be too early as it may give false-positive results due to fibrosis and scarring.

New clinical diagnostic criteria for eosinophilic chronic rhinosinusitis.

OBJECTIVE: Chronic rhinosinusitis is a heterogeneous disease. Most cases of chronic rhinosinusitis with nasal polyp(s) (CRSwNP) in Western countries show a strong tendency for recurrence after surgery and pronounced eosinophil infiltration in the nasal polyps. The prevalence of CRSwNP with pronounced eosinophilic inflammation is steadily increasing and is classified as eosinophilic chronic rhinosinusitis (ECRS) in Japan. However, less than 50% of CRSwNP patients in Japan and East Asia show such features. Since the treatment strategy of ECRS differs from that of non-ECRS, clinical diagnostic criteria that distinguish ECRS from non-ECRS are needed. METHODS: A total of 124 patients with CRSwNP patients who underwent endonasal sinus surgery were classified as ECRS or non-ECRS according to their clinical characteristics and the clinical features of the two groups were compared. Computed tomography (CT) images of the sinuses were graded according to the Lund-Mackay system. We also graded CT images of the olfactory cleft. Blood examination findings, sinus CT images and asthma complications were analyzed by multivariate logistic regression. Clinical findings that were significantly different between ECRS and non-ECRS were analyzed by receiver operating characteristic curves to determine optimal predictors of ECRS. RESULTS: Blood eosinophilia, asthma complications and CT image scores were significantly different between ECRS and non-ECRS. In particular, increased blood eosinophil percentage and CT image scores for the posterior ethmoid and the olfactory cleft showed good accuracy as predictors of ECRS. A combination of the cut-off values for three predictors (increased blood eosinophil percentage above the normal range, olfactory cleft score ≥1 and posterior ethmoid score ≥1) indicated high accurate diagnostic ability (sensitivity, 84.6%; specificity, 92.3%). CONCLUSION: A set of three clinical findings can differentiate ECRS from non-ECRS with high accuracy, even when these findings are assessed in regular outpatient clinics.

Examination of the optimal condition on the in vitro sensitivity to telomelysin in head and neck cancer cell lines.

OBJECTIVE: Telomelysin (OBP-301) is a telomerase-specific replication-competent adenovirus with a human telomerase reverse transcriptase (hTERT) promoter. Telomelysin has a strong antitumor effect on a variety of cancers, including head and neck squamous cell carcinoma (HNSCC), and combining telomelysin treatment with paclitaxel or cisplatin enhances the antitumor effect on HNSCC. In the present study, we investigated the relationship between the antitumor activity of telomelysin and tumor cell doubling time(DT), S-phase fraction, and E1A expression. We also investigated whether the antitumor effects of OBP-301-resistant tumor cells are enhanced by cisplatin, paclitaxel, or streptolysin O. METHODS: The tumor cell DT of 17 human HNSCC cell lines was examined. Antitumor activities of telomelysin (OBP-301) for each HNSCC cell line were examined by MTT assay. Cell cycle analysis was conducted by flowcytometry. E1A gene expressions after infection with telomelysin, hTERT, CAR (Cocksackie Adenovirus Receptor), and c-Myc were examined by quantitative PCR, and E1A expressions were examined again after pretreatment with cisplatin, paclitaxel, or streptolysin O. Correlations were analyzed by Spearman's correlation coefficient. RESULTS: There was a significant relationship between telomelysin sensitivity and DT, S-phase fraction and early E1A expression, and pretreatment with cisplatin, paclitaxel, and streptolysin O increased infectivity of telomelysin-resistant HNSCC cell lines. CONCLUSION: These findings are useful for advancing clinical trials, and suggest that adjuvant telomelysin treatment would be effective even in telomelysin-resistant HNSCC cell lines.

Morphological characteristics and peptidergic innervation in the carotid body of spontaneously hypertensive rats.

We examined morphological characteristics of the carotid body of spontaneously hypertensive rats (SHR), those of age-matched normotensive Wistar rats (NWR), and age-matched genetically comparable Wistar Kyoto rats (WKY). We examined the distribution and abundance of four different regulatory neuropeptides: substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), and neuropeptide Y (NPY) in the carotid bodies of these three strains of rats. The carotid bodies of SHR were larger than those of NWR and WKY. The values of the long axis of the carotid bodies of SHR were significantly larger (1.3 times) than those of NWR and WKY. In the carotid bodies of SHR, the percentage of relatively large vessels was similar to that of the carotid bodies of WKY, although the carotid bodies themselves were significantly larger than in WKY. The density of VIP varicose fibers in the carotid bodies of SHR was lower than in the carotid bodies of WKY, although the density of SP, CGRP and NPY fibers was similar to that of the carotid bodies of NWR and WKY. These findings suggested that VIP was unrelated to enlargement of the carotid body of SHR, but it might modify the sensitivity of chemoreceptors in the carotid body.

Efficacy and toxicity of concurrent chemoradiotherapy in patients with advanced oropharyngeal squamous cell carcinoma.

PURPOSE: The aim of this study was to evaluate the feasibility and toxicity of concurrent chemoradiotherapy (CCRT) with docetaxel, cisplatin (CDDP) and 5-fluorouracil (5-FU) (TPF regimen) or with CDDP, 5-FU, methotrexate and leucovorin (PFML regimen) in previously untreated patients with advanced oropharyngeal squamous cell carcinoma (SCC). METHODS: Fifty-six eligible patients with stage III or IV oropharyngeal SCC were treated with CCRT. Forty-four patients were men and 12 were women, and the average age of the patients was 58.8 years (range, 37-72 years). In the TPF group, patients received CCRT with the TPF regimen [docetaxel (50 mg/m(2), day 1), CDDP (60 mg/m(2), day 4) and a continuous 5-FU infusion (600 mg/m(2)/day, days 1-5)]. In the PFML group, patients received CCRT with the PFML regimen [CDDP (60 mg/m(2), day 4), a continuous 5-FU infusion (600 mg/m(2)/day, days 1-5), methotrexate (30 mg/m(2), day 1) and leucovorin (10 mg/m(2)/day, days 1-5)]. The total radiation dose was between 66.6 and 70.2 Gy. RESULTS: The overall 5-year survival rate was 64.6% in all patients, 68.6% in the resectable group and 47.4% in the unresectable group. The 5-year disease-specific survival rate was 72.2% in all patients, 78.1% in the resectable group and 47.7% in the unresectable group. Regarding clinical stage, the 5-year disease-specific survival rates were 91% in stage III, 72% in stage IVa and 44% in stage IVb. CONCLUSION: CCRT with TPF or PFML regimen for advanced oropharyngeal SCC is tolerable and effective, especially in patients with resectable disease.

Mucosal melanoma of the head and neck.

Mucosal melanoma of the head and neck (MMHN) is a rare malignant tumor associated with a poor prognosis. A retrospective study of case records of patients treated at our department between 1992 and 2010 was carried out. Thirteen patients were enrolled. The median age of the patients (3 males and 10 females) was 61 years (range 39-78). The median follow-up period was 48 months (range 10-115). Two common primary sites were the nasal cavity (8 cases) and sinonasal complex (5 cases). Ten patients (77%) received curative surgery. Chemotherapy was administered to 10 patients. In addition, lymphokine-activated killer (LAK) cell therapy was administered to 7 patients as adjunctive immunotherapy after the initial treatment course. The overall 5-year, cause-specific survival rate was 56%. Patients who received adjunctive LAK cell therapy had a survival rate of 67% at 5 years, while patients who did not receive adjunctive LAK cell treatment had a survival rate of 33%. MMHN is associated with a poor survival rate. The most common cause of death is distant metastasis. Surgery, radiotherapy and chemotherapy are common strategies for MMHN, but the control of metastasis is difficult. The use of immunotherapy remains uncommon for MMHN. However, from the viewpoint of a systemic disease, due to its high rate of metastases, immunotherapy using LAK cell treatment may contribute to the improvement of prognosis in patients with MMHN.

Role of 18F-FDG PET in detecting primary site in the patient with primary unknown carcinoma.

The aim of this study was to verify the effectiveness of positron emission tomography (PET) in detecting primary sites in carcinoma of unknown primary (CUP) patients. In this study, CUP represented a group of heterogeneous tumors that shared the clinical manifestation of metastatic carcinoma with no obvious primary site at the time of first diagnosis, which included clinical investigations, computed tomography, magnetic resonance imaging and panendoscopy. We reviewed the records of 24 patients with CUP between January 1995 and December 2009. The patients who demonstrated additional tracer uptake sites other than previously known metastatic lesions by PET scan were done direct biopsies for the sites of accumulation. Patients who had a negative PET scan or for whom the primary site could not be identified by direct biopsies underwent examination under anesthesia of the at-risk occult tumor sites. PET scan demonstrated focal accumulation suspicious for primary tumor in 12 (50.0%) of 24 patients: tonsil 5, nasopharynx 3, hypopharynx 1, tongue 1, larynx 1, and maxillary sinus 1. A subsequent biopsy of these sites revealed primary cancer in 9 (37.5%) of 24 patients: tonsil 5, nasopharynx 1, hypopharynx 1, tongue 1, and maxillary sinus 1. In the remaining three patients, no malignant cells were found by the biopsy of the accumulated area: nasopharynx 2, larynx 1. PET scans increase the yield of primary tumor by 37.5%. The sensitivity, specificity for PET scan were 80.8, 76.9%, respectively. PET scanning is useful in detecting primary cancer of CUP patients.

[Study of cerebellar infarction with isolated vertigo].

Isolated vertigo is generally attributed to labyrinthine disease, but may also signal otherwise asymptomatic cerebellar infarction. Of 309 subjects admitted between April 2004 and March 2009 for the single symptom of acute vertigo initially thought to be labyrinthine, four were found to have cerebellar infarction of the posterior inferior cerebellar artery area (PICA). All were over 60 years old and had risk factors including hypertension, diabetes mellitus, arrhythmia, and/or hyperlipidemia. Two had trunk ataxia, with magnetic resonance imaging (MRI) showing infarction within a few days. The other two could walk without apparent trunk ataxia, however, it took 4 to 7 days to find the infarction, mainly through neurological, neurootological, and MRI findings. Neurologically, astasia, dysbasia or trunk ataxia were important signs. Neurootologically, nystagmus and electronystagmographic testing involving eye tracking, saccade, and optokinetic patttens were useful.

[A case of thyroid crisis in acute tonsillitis treatment].

We report a case of fatal thyroid crisis induced by acute tonsillitis. A 33-year-old woman with untreated hyperthyroidism developed thyroid crisis during acute tonsillitis treatment. The four days passing from crisis onset to treatment initiation unduly compromised her condition, resulting in death. Such cases point up the need for prompt thyroid crisis diagnosis and treatment, the difference between a proactive life-sustaining response and a negative mortal result.