[A case report: a repeated cerebrospinal fluid otorrhea].

Cerebrospinal fluid (CSF) otorrhea, leakage of CSF through the ear structures, may occur from a traumatic or operative defect in the skull, tumor, cholesteatoma, or congenital anomalies. A case of repeated CSF otorrhea is uncommon. In this report, we presented a case of a repeated CSF otorrhea which occurred a decade after the first middle ear surgery for chronic otitis media. The first CSF leakage, which might have been due to bone defects in the tegmen at the first middle ear sutgery, was surgically repaired using a transmastoid approach. However, CSF leakage with a meningoencephalocele occurred again 8 years after our first surgery for the CSF and the fistula was repaired using a transmiddle cranial fossa approach. Although 2 years have passed since the surgery, the CSF leakage has not recurred.

Clinical outcomes of microscopic decompression for degenerative lumbar foraminal stenosis: a comparison between patients with and without degenerative lumbar scoliosis.

We performed microscopic lumbar foraminotomy in all the patients diagnosed with degenerative lumbar foraminal stenosis (DLFS) and retrospectively reviewed the clinical outcomes and the factors influencing them. The preoperative Japanese Orthopaedic Association (JOA) score of 13.8 significantly improved to 21.9 postoperatively. Although leg pain reduced in 44 patients (95.7%) immediately after surgery, it recurred in 9 patients (19.6%). The recurrence frequency was significantly higher and the JOA score improvement ratios significantly lower in patients with degenerative lumbar scoliosis (DLS) than in those without DLS. Even among patients with DLS, those with <3° Cobb angle difference between the supine and standing positions showed satisfactory results, with no recurrence. In conclusion, microscopic lumbar foraminotomy for DLFS produced satisfactory clinical outcomes even in patients with DLS. However, the outcomes were poor in patients with unstable DLS.

Open-door laminoplasty with stand-alone autologous bone spacers: evaluation of enlarged laminar arch with CT-multiplanar reconstruction.

OBJECTIVE: The authors aimed to determine the efficacy of open-door laminoplasty with stand-alone autologous bone spacer for preserving enlarged lamina in patients with cervical myelopathy. METHODS: Patients who underwent open-door laminoplasty for cervical myelopathy with stand-alone autologous bone spacer and underwent CT 1 week and 1 year after surgery were included in this study. There were 20 men and 13 women, with an average (range) age of 65.0 (37-86) years. Seventeen patients were younger than 70 years, and 16 patients were older than 70 years. Autogenous bone spacers made from spinous processes were used in all patients. Slits were made on both sides of the spacers. The lamina was raised with a curette, and a spacer was inserted without any sutures. Before surgery and 1 week and 1 year after surgery, the anteroposterior diameter (APD) of the spinal canal was measured using midsagittal-plane CT-multiplanar reconstruction. The bone union rate of the hinge side and autogenous bone spacer of each lamina was determined using CT images obtained 1 year after surgery. Results 1 year after surgery were evaluated using Japanese Orthopaedic Association (JOA) score. RESULTS: The mean ± SD APD increase rate was 56.3% ± 21.3% 1 week after surgery and 51.7% ± 20.6% 1 year later. The average APD decrease rate was 2.9% ± 3.8%. The bone union rate on the hinge side was 100%, and that of autologous bone spacer was 93.8% 1 year after surgery. The mean APD decrease rate was 3.3% in patients younger than 70 years and 2.3% in those older than 70 years. There was no significant difference between the two groups (p > 0.05, nonpaired t-test). The JOA score averaged 10.1 before surgery and 13.3 a year after surgery (total score 17). The average improvement rate was 46.3% ± 26.4%. CONCLUSIONS: The authors devised and implemented a technique for inserting an autologous bone spacer between the opened lamina and lateral mass without sutures. The enlarged spinal canal was maintained 1 year after surgery. This simple method does not require any instrumentation or additional cost to stabilize the opened lamina.

Efficacy of concurrent chemoradiotherapy for T1 and T2 laryngeal squamous cell carcinoma regarding organ preservation.

BACKGROUND: Although the survival rate of early-stage laryngeal squamous cell carcinoma (SCC) patients treated by radiotherapy (RT) is sufficient, the larynx preservation rate is unsatisfactory. To improve the larynx preservation rate, such patients have been treated by RT with chemotherapeutic agents. PATIENTS AND METHODS: RT with or without uracil-tegafur (UFT) was performed for T1 cases, and UFT and carboplatin for T2 cases. RESULTS: In T1 cases, 30 patients received RT and 16 patients received concurrent chemoradiotherapy (CCRT). In T2 cases, 28 patients received RT and 45 patients received CCRT. There were no significant differences in the response and survival rates between the treatment methods both in T1 and T2 cases. The 5-year larynx preservation survival rate was improved significantly by CCRT in T2 cases (66.7% vs. 93.3%; p < 0.01). CONCLUSION: CCRT for early-stage laryngeal SCC patients was efficacious to improve the larynx preservation survival rate.

Antiemetic effects of granisetron and dexamethasone combination therapy during cisplatin-containing chemotherapy for head and neck cancer: dexamethasone dosage verification trial.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) remains a significant problem for patients and is associated with a substantial deterioration in quality of life; appropriate use of antiemetic drugs is crucial in maintaining the quality of life in patients undergoing chemotherapy. METHODS: This randomized, crossover trial evaluated the antiemetic efficacy and safety of 8 mg per day (low-dose) and 16 mg per day (standard-dose) dexamethasone, in combination with the 5-HT(3) receptor antagonist granisetron, in 36 patients receiving cisplatin (CDDP)-containing chemotherapy for head and neck cancer. Following chemotherapy, the antinausea/vomiting inhibition rate for each dexamethasone dose was measured. RESULTS: During the 24-h period following administration of chemotherapy (acute phase), the antinausea/vomiting inhibition rates (no nausea and no episodes of vomiting) for 8 mg and 16 mg dexamethasone were comparably high (58.3% and 63.8%, respectively; P = 0.8092). Similar results were seen on days 2-5 following chemotherapy. Efficacy during the acute phase, based on the number of instances of vomiting and degree of nausea, was also comparably high for the two dexamethasone doses (overall efficacy rates were 94.4% and 88.8%, respectively, for 8 mg and 16 mg dexamethasone; P = 0.7637). Both doses maintained an 80% or higher response rate until day 3, and neither dose produced severe side effects. CONCLUSION: The results suggest that granisetron and dexamethasone combination therapy is useful in controlling acute and delayed nausea and vomiting induced by CDDP-containing chemotherapy for head and neck cancer. Furthermore, 8 mg and 16 mg dexamethasone have equivalent antiemetic efficacy.

[Successful treatment results of S-1 administration in 2 patients, one with a remnant tumor of the larynx and metastatic tumors to the lung, and another with a metastatic tumor in the neck from the hypopharynx].

We report two successful remnant and recurrent cases of head and neck cancer treated with S-1. Case 1, a 52-year-old man, was diagnosed as supraglottic laryngeal carcinoma (T3N2cM0, squamous cell carcinoma: SCC) on January 25, 2000, and concurrent chemoradiotherapy (CCRT) was applied. After the treatment, a remnant tumor in the larynx was found by biopsy. He was followed using UFT at 400mg/day because he had refused surgery. Pulmonary metastasis was detected by chest CT on June 14, 2001, and the administration of S-1 was started. After 2 courses, the mass in the lung disappeared, and the primary lesion was also judged to be a complete response(CR). The administration of S-1 is still continuing and remnant tumors have not been found. Case 2, a 76-year-old man, was diagnosed with hypopharyngeal carcinoma (T3N2bM0, SCC) on December 14, 2001, and CCRT was applied resulting in CR in the hypopharynx and the neck. He was followed using UFT at 300 mg/day after discharge. A supraclavicular lymph node became palpable on March 27, 2003. Pathological examination by fine needle aspiration cytology showed SCC, class V. After 2 courses administering S-1 at 100mg/day, the supraclavicular lymph node disappeared. S-1 was changed to UFT at 300 mg/day on July 31, 2003, because adverse events of grade 3 appeared. Administration of UFT was continued for one year. No recurrence has been found for 5 years.

[The role and limitations of FDG-PET in head and neck cancer].

18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a nuclear medicine imaging technique which has been increasingly applied as a diagnostic tool. The usefulness of FDG-PET may be described as follows: I . Early detection of cancer; II. Diagnosis of cancer; III. Detection of nodal or distant metastasis, and double cancer; IV. Detection of unknown primary tumor with metastatic neck lesions; and V. Evaluation of treatment of head and neck cancer. FDG-PET is especially useful to detect distant metastasis, double cancer with head and neck cancer and unknown primary tumor with metastatic neck lymph nodes. The conventional modalities, e. g., CT or MRI, show anatomical images in the body. On the other hand, FDG-PET reveals three-dimensional images of functional processes of the glucose metabolism. FDG-PET can estimate metabolic activity in cancer and is useful in evaluating or monitoring the response to concurrent chemoradiotherapy of the head and neck cancer. However, we should recognize the limitations of FDG -PET. An acute inflammatory disease shows high FDG uptake like cancer. It is difficult to detect early-stage esophageal cancer or to diagnose parotid gland cancer.

Novel in situ visualisation of rat intestinal absorption of polyphenols via matrix-assisted laser desorption/ionisation mass spectrometry imaging.

Matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) is presently used in physiological evaluations for visualisation of targets in organs. In the present study, MALDI-MSI was used as a visualisation technique to investigate the intestinal absorption of polyphenols. Nifedipine/phytic acid-aided MALDI-MSI was performed to visualise theaflavin-3'-O-gallate (TF3'G) and epicatechin-3-O-gallate (ECG) in the rat jejunum for 50-µM, 60-min transport experiments. Non-absorbable TF3'G was successfully visualised at the apical region, whereas absorbable ECG was detected throughout the rat jejunum. MALDI-MSI was also performed to determine the transport routes of the target metabolites. Signals corresponding to TF3'G and ECG in the membranes were diminished following treatment with inhibitors targeting the monocarboxylic acid transporter and organic anion transporting polypeptides. Enhanced visualisation of TF3'G was achieved by inhibiting efflux routes. Our findings demonstrated that the present MALDI-MSI can provide critical spatial informations on intestinal absorption of targets, by which TF3'G and ECG were incorporated into intestinal tissues, followed by efflux back to the apical compartment. In addition, MALDI-MSI analyses suggested that TF3'G was resistant to phase II metabolism during the influx/efflux processes, whereas ECG was susceptible to methylation and sulphation reactions. In conclusion, inhibitor-aided MALDI-MSI could serve as a powerful in situ visualisation technique for verifying intestinal transport routes and investigating the metabolism of penetrants.

Antitumor effect of gefitinib on head and neck squamous cell carcinoma enhanced by trastuzumab.

The overexpression of EGFR and/or HER-2 is associated with tumor cell resistance to chemotherapy, radiotherapy, disease progression and poor prognosis in patients with a variety of malignant tumors. Treatment combining the EGFR-targeting drug, gefitinib (ZD1839, Iressa) with the HER-2-targeting drug, trastuzumab (Herceptin) has been reported to improve therapeutic efficacy in patients with breast cancer. The purpose of this study was to examine the antitumor effect of this combination on head and neck squamous cell carcinoma (HNSCC) in vitro. Cell proliferation was inhibited significantly in two cell lines. Although IC50 of gefitinib alone against some cell lines was not reached, it was achieved after being combined with trastuzumab. Furthermore, IC50 was lower for the combination than for gefitinib alone in several cell lines. These results suggest that the combination may improve efficacy against HNSCC.

Early assessment of clinical response to concurrent chemoradiotherapy in head and neck carcinoma using fluoro-2-deoxy-d-glucose positron emission tomography.

OBJECTIVES: The aim of this study is to assess the utility of FDG-PET in the evaluation of therapeutic effects at 4 weeks after the completion of the concurrent chemoradiotherapy (CCR) in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Thirty-one patients with previously untreated HNSCC were retrospectively investigated about FDG-PET, CT, MRI and biopsies of the carcinoma before and 4 weeks after the treatment. RESULTS: The results of pathological examinations after CCR showed 6 residual cases and 25 ones with a pathologically complete response (pCR). The specificity of FDG-PET was 80%, although the sensitivity was limited to 67%. CONCLUSIONS: FDG-PET has a high specificity but limited sensitivity to discriminate residual cancer from fibrosis or scar at 4 weeks after CCR. FDG-PET at 4 weeks after CCR was too early to perform because of limited sensitivity.

Anti-tumor effects of bevacizumab in combination with paclitaxel on head and neck squamous cell carcinoma.

Human tumors are dependent on angiogenesis for growth, and the vascular endothelial growth factor (VEGF) is a major regulator of this process. Bevacizumab (Avastin), a monoclonal antibody directed against VEGF, has shown promise in treating a variety of cancers. In this study, we first examined the anti-tumor effects of bevacizumab on head and neck squamous cell carcinoma (HNSCC). Then we examined the effects of bevacizumab combined with paclitaxel, a chemotherapeutic agent, in HNSCC. This is the first demonstration of the anti-tumor effects of bevacizumab on HNSCC. In vitro, bevacizumab did not show any antiproliferative effects against the HNSCC cell lines. However, in vivo, bevacizumab showed dramatic anti-tumor effects against HNSCC tumor xenografts in mice. In addition, treatment with a bevacizumab-paclitaxel combination resulted in a remarkable inhibition of the HNSCC tumor xenografts, compared to the effects of each agent separately. A decreased blood vessel density and an increased apoptotic index were seen in the shrunken tumors. These results suggest that bevacizumab in combination with paclitaxel could have useful clinical application in HNSCC.

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

Angiogenesis is required for tumor growth and metastasis and, therefore, represents a target for cancer treatment. While many factors have been implicated in promoting angiogenesis, vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis. ZD6474 is a potent VEGF receptor-2 (VEGFR-2) tyrosine kinase inhibitor which also has activity against the epidermal growth factor receptor (EGFR) tyrosine kinase. The purpose of this study was to investigate the sensitivity of head and neck squamous cell carcinoma (HNSCC) cell lines to ZD6474, and to evaluate its antitumor efficacy on HNSCC xenografts. This is the first demonstration of antitumor effects of ZD6474 on HNSCC. In vitro ZD6474 displayed antiproliferative effects on HNSCC cells and inhibition of VEGFR-2 and EGFR pathways. In vivo ZD6474 displayed antitumor activity, induced apoptosis and antiangiogenic activity on nude mice bearing an established xenograft of YCU-H891 cells. These results suggest that ZD6474 has the potential to inhibit two key pathways in tumor growth via inhibition of VEGF-dependent tumor angiogenesis and via inhibition of EGFR-dependent tumor cell proliferation.

Prognostic value of retropharyngeal node involvement in CT-based lymph node-positive pharyngeal cancer following radiotherapy.

BACKGROUND: The objective of this study was to evaluate the impact of metastasis to the retropharyngeal nodes (RPN) in CT-based lymph node-positive head and neck patients by comparing other node levels. PATIENTS AND METHODS: A total of 175 CT-based lymph node-positive patients with carcinoma of the head and neck were managed with definitive radiation therapy. RPN involvement was identified only in pharyngeal cancer. One hundred and twenty-seven patients were investigated using CT and MRI following the guidelines on CT-based elective nodal delineation. Fifty-two patients received induction chemotherapy and 58 received concurrent chemoradiotherapy. RESULTS: RPN involvement and lymph node size were identified as having a significant effect on the disease-free survival (DFS) in univariate analysis. Concurrent chemotherapy and RPN involvement significantly affected DFS on multivariate analysis in all pharyngeal cancer patients and non-nasopharyngeal cancer (NNP) patients. RPN involvement, level IV involvement and concurrent chemotherapy also significantly affected locoregional control. CONCLUSION: Our study confirmed a poor outcome was associated with RPN involvement in patients with CT-based node-positive pharyngeal cancer and NNP patients definitively treated by radiotherapy.

Antitumor effects of Nafamostat mesilate on head and neck squamous cell carcinoma.

OBJECTIVE: Nafamostat mesilate (FUT-175), a synthetic serine protease inhibitor, has antitumor activities toward adenocarcinoma, e.g., colon cancer. However, its antitumor effects on other types of cancer have been less extensively studied. We investigated the biological activities of Nafamostat mesilate on cell proliferation, cell-invasive potential and growth factor production in head and neck squamous cell carcinoma (HNSCC). METHODS: Two human HNSCC cell lines established in our department, YCU-L891 and -H891, and a human vulvar squamous cell carcinoma cell line, A431, were examined for the effect of Nafamostat mesilate. The effects on cell growth were evaluated using the MTT assay. The effects on the relative expression levels of mRNA were measured by quantitative RT-PCR. Cytokine secretion was analyzed by enzyme-linked immunosorbent assay. RESULTS: Nafamostat mesilate inhibited the proliferation of two HNSCC cell lines, YCU-L891 and YCU-H891, and A431. In these cell lines, Nafamostat mesilate down-regulated both matrix metalloproteinase (MMP)-2 and -9. In addition, it reduced the productions of vascular endothelial growth factor (VEGF) and transforming growth factor beta1 (TGF-beta1) by the tumor cells. CONCLUSION: Our results suggest that Nafamostat mesilate has potential for use as a treatment against local growth, invasion and metastasis of squamous cell carcinoma.

Concurrent chemoradiotherapy for T4 patients with hypopharyngeal and laryngeal squamous cell carcinomas.

OBJECTIVES: Concurrent chemoradiotherapy (CCR) was given for the previously untreated T4 hypopharyngeal and laryngeal squamous cell carcinoma patients and the response and survival rates were evaluated. PATIENTS AND METHODS: A total of 23 patients, namely, 15 for hypopharynx and 8 for larynx were eligible. These patients were given cisplatin and 5-fluorouracil based chemotherapeutic regimens with conventional radiotherapy for a total dose of 66.6-70.2 Gy. RESULTS: Ten out of the 15 hypopharyngeal carcinoma patients and 4 out of the 8 laryngeal carcinoma patients showed a complete response at the primary sites. The 5-year disease-specific survival rate was 59.4% in all the patients, 51.9% in the hypopharyngeal carcinoma patients, and 71.0% in the laryngeal patients. Seven out of the 12 resectable hypopharyngeal carcinoma patients and 4 out of 8 laryngeal carcinoma patients were able to do without total laryngectomy. CONCLUSIONS: Based on these results, the survival rate in the hypopharyngeal and laryngeal T4 carcinoma patients treated by CCR seems to be satisfactory and the possibility of organ preservation for the advanced patients is indicated.

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

Taxanes, a new class of antitumor drugs, are effective against a large number of human tumors, although there are problems with drug resistance. The novel taxane, IDN5109, is characterized by its high tolerability, antitumor efficacy, ability to overcome multidrug resistance, and oral bioavailabilty. We investigated the cellular response of IDN5109 to head and neck squamous cell carcinoma (HNSCC), and compared the antitumor activity of IDN5109 with that of paclitaxel. This is the first demonstration of antitumor effects of IDN5109 on HNSCC. In in vitro experiments, IDN5109 showed antiproliferative effects against HNSCC cell lines. After treatment with IDN5109, Bcl-2 and Bcl-XL were down-regulated, Bax was up-regulated, and caspase-3 was activated. After treatment with IDN5109, concentrations of both VEGF and IL-8 in the culture supernatant of HNSCC cells decreased. In in vivo experiments, the oral administration of IDN5109 showed antitumor effects against HNSCC tumor xenografts. Immunohistochemistry showed that IDN5109 inhibited tumor angiogenesis and induced apoptosis in HNSCC cells, producing a decreased blood vessel density and increased apoptosis index. On the basis of these results, IDN5109 is useful as a chemotherapeutic agent against HNSCC.

A case of osteochondroma of the atlas causing obstructive sleep apnea syndrome.

Most osteochondromas affect the long bones, but rarely originate in the spine. We report an extremely rare case of osteochondroma of the atlas causing obstructive sleep apnea syndrome (OSAS) in a 61-year-old female. The osteochondroma was removed completely using a transoral approach, and the symptoms of OSAS disappeared. A review of the literature regarding osteochondroma confirms the rarity of this lesion and the use of a transoral approach is discussed.

Concurrent chemoradiotherapy with cisplatin, 5-fluorouracil, methotrexate, and leucovorin in patients with advanced resectable squamous cell carcinoma of the larynx and hypopharynx.

CONCLUSIONS: This regimen of concurrent chemoradiotherapy was safe and well tolerated. In terms of larynx preservation, the present regimen appears to be useful for patients with advanced resectable squamous cell carcinoma (SCC) of the larynx and hypopharynx. OBJECTIVES: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy in patients with advanced resectable SCC of the larynx and hypopharynx, and to demonstrate the feasibility of larynx preservation. PATIENTS AND METHODS: Forty-six eligible patients were treated. The chemotherapy regimen consisted of a combination of four drugs: cisplatin (60 mg/m(2), day 4), 5-fluorouracil (5-FU) (600 mg/m(2) given continuously for 120 h, days 1-5), methotrexate (MTX) (30 mg/m(2), day 1), and leucovorin (LV) (20 mg/m(2), days 1-5). Two cycles of this regimen were given every 4 weeks during radiotherapy. Radiotherapy was delivered 5 days a week using a single daily fraction of 1.8-2.0 Gray, to a total dose of 66.6-70.2 Gray. RESULTS: The 3-year disease-specific survival rates of patients with laryngeal or hypopharyngeal SCC were 81.3% and 78%, respectively. The 3-year disease-specific survival rates with larynx preservation of patients with laryngeal or hypopharyngeal SCC were 46.7% and 59%, respectively. The main toxicities were neutropenia, dermatitis, mucositis, and infection.

Fibromatous polyp of the hypopharynx.

We treated a patient with hypopharyngeal fibromatous polyp and speculated the mechanism of this disease. Fibromatous polyp, consisting of fibrous tissue hyperplasia with small vessels, fatty cells and inflammatory cells, is a clinically diagnostic name. Most of pharyngeal fibromatous polyps are arising from the palatine tonsil, and those from the pharyngeal epithelium are rare. The greater part of hypopharyngeal tumors is squamous cell carcinomas, and benign tumors are really uncommon. Fibromatous polyp is not thought to be a true tumor, but the symptoms are almost the same as tumorous diseases, e.g., discomfort in the throat, swallowing difficulty and respiratory distress. Complete resection is used as the treatment method. We operated on this patient under a laryngoscope and successfully resected the polyp. Five months after the operation, there is no sign of recurrence and the patient has no symptoms. This type of polyp is considered to enlarge gradually and it can cause asphyxia and/or dysphagia, so complete ablation should be performed as soon as possible.

Maxillary sinus carcinoma: the only symptom was neck lymph node swelling.

OBJECTIVE: Since maxillary sinus is composed of bone structure, the main symptoms of maxillary sinus carcinoma are related to the anatomical feature and the destructive lesion of the bony wall, such as cheek pain and nasal obstruction. METHODS: We report a female case with undifferentiated carcinoma in the right maxillary sinus, only appearing cervical swelling which was revealed as lymph node metastasis. RESULTS: CT and MRI findings showed just maxillary sinusitis with minor bone destruction. However, fluorine 18-labelled deoxyglucose positron emission tomography (FDG-PET) was useful for the detection of the primary site. The patient received concomitant chemoradiotherapy, and showed a complete response both in the primary site and neck lymph nodes. She has no recurrence for 18 months after the primary therapy. CONCLUSION: The main symptoms of maxillary sinus carcinoma are related to the local progression, and known to have less cervical lymph node metastasis. However, like the present case, there is a rare case that has no symptom and organic features associated with the local mass. With the best use of advanced diagnostic technique, e.g., FDG-PET, we could diagnose and treat atypical maxillary sinus carcinoma patients.