Seiji Hosokawa

Epidemiological analysis of nasopharyngeal carcinoma in the central region of Japan during the period from 1996 to 2005

OBJECTIVE It has become clear through epidemiological analysis that the incidence of cancers of the lung, liver, colon, and rectum are increasing in Japan every year. However, there have been few epidemiological analyses of nasopharyngeal carcinoma (NPC) in Japan. The aim of this study was to analyze the epidemiology and current incidence of NPC in the Chubu region of Japan during the period from 1996 to 2005. METHODS Takeshita et al. conducted a similar investigation in the Chubu region 10 years ago, and, as a result, this is a comparative study. The Chubu region is the central region of Japanese main island. We researched NPC patients treated in hospitals in each prefecture over a 10-year period (1996-2005) using a questionnaire. RESULTS A total of 525 cases (male:385, female:134, unknown:6) were analyzed epidemiologically, histologically, serologically, and clinically in this study. The incidence per 10(5) population per year was 0.29. For the period of 1986-1995, the age-standardized incidence of NPC was 0.28 per 10(5) persons per year in Takeshitas report. There was no significant difference between the two periods. The ages of the patients ranged from 13 to 90 years. The mean age of was 55.2 years. On the basis of the World Health Organization (WHO) histological criteria, 36% of the patients were classified as WHO I, 27% as WHO II, and 37% as WHO III. Carcinoma was located in the posterosuperior region in 56%, lateral in 41%, and inferior in 3%. Tumor staging showed that 6% to belonged to stage I, 25% to stage II, 31% to stage III, and 38% to stage IV. A neck mass was present in 52% of the patients, ear symptoms in 48%, nasal symptoms in 27%, headaches in 10%, pharyngeal symptoms in 9%, ophthalmologic symptoms in 9%, and cranial neurological symptoms in 9%. The positive rates of serum titers of the antibodies to Epstein-Barr virus (EBV)-related antigens were calculated. The positive rate of anti-EBV-viral capsid antigen (VCA) immunoglobulin (Ig) G titers was 58.6%, that of anti-EBV-VCA IgA titers was 53.6%, and that of EBNA was 81%. The five-year survival rate for all patients was 67.6%, and that for those in stage I, II, III, and IV was 75%, 84%, 69%, and 53%, respectively. The five-year survival rate for stage IV was significantly lower than those for the other stages (P<0.05). CONCLUSION The age-standardized annual incidence of NPC in our survey was 0.29 per 10(5) persons per year, being relatively low and stable.

Tortuous internal carotid artery presenting as a pharyngeal mass

BACKGROUND Deformities of the carotid artery are rare. Tortuosity, kinking and coiling of the internal carotid artery may be observed with advancing age. A tortuous internal carotid artery may cause an abnormal sensation in the throat. In the early twentieth century, there were several reported cases of fatal haemorrhage during pharyngeal surgical procedures, because this condition went undetected. METHOD AND RESULTS We present two cases of tortuosity of the right internal carotid artery. Both women complained of abnormal throat sensations. Endoscopic studies and radiological examinations revealed tortuous right internal carotid arteries presenting as pulsatile masses. A literature review revealed that, in most reported cases, this deformity occurred on the right side. We believe that the defect and its right-sided predominance can be attributed to anatomical influences and factors affecting blood pressure. CONCLUSION In most reported cases of tortuous internal carotid artery, the defect occurred on the right side and patients complained of an abnormal sensation in the throat. This information is useful in the diagnosis of this condition. It is important for otolaryngologists to recognise this anomaly, because fatal haemorrhage can occur in patients with this condition during surgical procedures on the pharynx.

The effect of ventilation tube insertion or trans-tympanic silicone plug insertion on a patulous Eustachian tube

Abstract Conclusions This study suggests that long-term ventilation tube insertion is the first-choice surgical treatment for a ‘sniff-type’ patulous Eustachian tube (PET). When treating a refractory PET, it is important to determine whether the patient had a habitual sniff. Objectives PET patients were divided into two groups: patients with a habitual sniff (sniff-type PET) and those without a habitual sniff (non-sniff-type PET). This study examined the effects of ventilation tube insertion or silicone plug insertion in each group. Methods Surgical procedures such as ventilation tube insertion or trans-tympanic silicone plug insertion were performed for these patients. Tubotympanoaero-dynamic graphy (TTAG) was also performed to determine the mechanisms underlying these treatments. Results There were 11 cases (17 ears) of sniff-type PET and 20 cases (27 ears) of non-sniff-type PET. An improvement in symptoms was found in 72.7% of the patients who underwent silicone plug insertion (66.7% for sniff-type PET and 74.1% for non-sniff-type PET) and in 90.9% of the patients who underwent ventilation tube insertion for sniff-type PET. In TTAG assessments, many sniff-type PET patients showed significant synchronous changes at high levels of pressure (over 40 daPa) in the external auditory meatus and nasopharynx when performing a slight Valsalva manoeuvre (below 200 daPa).

Surgical approach for treatment of carcinoma of the anterior wall of the external auditory canal.

Objective Treatment outcomes for carcinomas of the external auditory canal (EAC) were evaluated regarding radiologic and pathologic factors. Study Design Retrospective case review. Setting University hospital. Patients Fifteen patients histologically diagnosed with carcinomas of the EAC. Intervention A radiologic and pathologic analysis was performed on these patients histologically diagnosed with carcinomas of the EAC and treated surgically at our institution. We evaluated the size of focal defects in the anteroinferior (AI) canal wall of the tympanic bone with preoperative computed tomographic (CT) scans. Histopathologic slides for the same patients were evaluated according to the same criteria as the CT scans. Main Outcome Measure Pathologic features and estimated survival rate. Results Preoperative CT scans of 15 temporal bones demonstrated an AI canal wall defect ranging from less than 1 mm to full-thickness destruction. Six of 15 patients had an AI canal wall defect greater than 2 mm on preoperative CT scan. Pathologic findings in these 6 cases showed extension of the tumor through the AI defect into the anterior soft tissues. Information on patients’ survival status was obtained after a median follow-up period of 78.3 months (range, 18–151 mo). Conclusion Preoperative CT can be used to accurately determine the pathologic extent of tumor invasion in carcinomas of the EAC. This diagnostic method facilitates exchange of accurate clinical data in a comparable form and can be used to evaluate the efficacy of existing and proposed treatments for EAC tumors.

Hyperbaric Oxygen Therapy as Adjuvant Treatment for Idiopathic Sudden Sensorineural Hearing Loss after Failure of Systemic Steroids

We evaluated the outcomes of and prognostic factors for idiopathic sudden sensorineural hearing loss (ISSNHL) treated with adjuvant hyperbaric oxygen therapy (HBOT). A retrospective review of clinical data was performed for 167 patients with ISSNHL who failed to respond to systemic steroids and were treated by adjuvant HBOT at Shizuoka Saiseikai General Hospital. We analysed the clinical outcomes, the averaged 5-frequency hearing level after systemic steroids, patient age, the interval between post-steroids and pre-HBOT, vertigo as a complication, the presence of diabetes mellitus, smoking history, and hypertension. Overall, after HBOT, complete recovery occurred in 16 (9.6%) of the patients, with definite improvement in 16 (9.6%) and slight improvement in 45 (26.9%). The overall rate of hearing improvement was higher in the study group (77/167 cases, 46.1%) than in the control group (52/160 cases, 32.5%; p = 0.021). If performed appropriately, HBOT should be able to improve hearing in many cases unresponsive to initial therapy.

Prognostic factors for idiopathic sudden sensorineural hearing loss treated with hyperbaric oxygen therapy and intravenous steroids.

OBJECTIVE This study evaluated the prognosis of idiopathic sudden sensorineural hearing loss when treated with hyperbaric oxygen therapy and intravenous steroids. METHODS The clinical data for 334 patients with idiopathic sudden sensorineural hearing loss treated by hyperbaric oxygen therapy and intravenous steroids at our hospital were retrospectively reviewed. These data included the initial averaged five-frequency hearing level, patient age, interval between onset of symptoms and treatment, vertigo as a complication, and co-existence of diabetes mellitus. RESULTS The overall improvement rate was 69.2 per cent, including better improvement (25.5 per cent), good improvement (21.0 per cent) and fair improvement (22.7 per cent). CONCLUSION Hyperbaric oxygen therapy appears to confer a significant additional therapeutic benefit when used in combination with steroid therapy for idiopathic sudden sensorineural hearing loss. If performed early, hyperbaric oxygen therapy may bring about hearing improvement in many patients who are unresponsive to initial therapy.

Undifferentiated sarcoma of the maxillary sinus: Report of a rare case in an adult

A 51-year-old man complained of left facial swelling and recurrent nasal bleeding. A giant solid tumor in the left maxillary sinus was detected on head CT and MRI, and this tumor was destroying the maxilla and extending into the orbit, pterygoid muscle and posterior paranasal sinuses. The resected specimen consisted of spindle cells containing necrotic material. Histological examination revealed immature tumor cells, and immunohistological study of the tumor showed staining was only positive for vimentin. We accordingly diagnosed undifferentiated sarcoma in the maxillary sinus. Combination chemotherapy with vincristine, doxorubicin, cyclophosphamide/ifosfamide with mesna and etoposide was administered; however, the tumor was unresponsive and the patient died after around 3 months.

Genes encoding neuropeptide receptors are epigenetic markers in patients with head and neck cancer: a site-specific analysis

Staging and pathological grading systems are useful but imperfect predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). To identify potential prognostic markers, we examined the methylation status of eight neuropeptide receptor gene promoters in 231 head and neck squamous cell carcinomas. The NPFFR1, NPFFR2, HCRTR1, HCRTR2, NPY1R, NPY2R, NPY4R, and NPY5R promoters were methylated in 80.5%, 79.2%, 67.1%, 73.2%, 35.1%, 36.4%, 38.5%, and 35.9% of the samples, respectively. In a multivariate Cox proportional hazards analysis, the odds ratio for recurrence was 2.044 (95% confidence interval [CI], 1.323-3.156; P = 0.001) when the NPY2R promoter was methylated. In patients without lymph node metastasis (n = 100), methylation of NPY2R (compared with methylation of the other seven genes) best correlated with poor disease-free survival (DFS) (odds ratio, 2.492; 95% CI, 1.190-5.215; P = 0.015). In patients with oral cancer (n = 69), methylated NPY1R and NPY2R were independent prognostic factors for poor DFS, both individually and, even more so, in combination (odds ratio, 3.90; 95% CI, 1.523-9.991; P = 0.005). Similar findings were observed for NPY2R and NPY4R in patients with oropharyngeal cancer (n = 162) (odds ratio, 5.663; 95% CI, 1.507-21.28; P = 0.010).Staging and pathological grading systems are useful but imperfect predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). To identify potential prognostic markers, we examined the methylation status of eight neuropeptide receptor gene promoters in 231 head and neck squamous cell carcinomas. The NPFFR1, NPFFR2, HCRTR1, HCRTR2, NPY1R, NPY2R, NPY4R, and NPY5R promoters were methylated in 80.5%, 79.2%, 67.1%, 73.2%, 35.1%, 36.4%, 38.5%, and 35.9% of the samples, respectively. In a multivariate Cox proportional hazards analysis, the odds ratio for recurrence was 2.044 (95% confidence interval [CI], 1.323–3.156; P = 0.001) when the NPY2R promoter was methylated. In patients without lymph node metastasis (n = 100), methylation of NPY2R (compared with methylation of the other seven genes) best correlated with poor disease-free survival (DFS) (odds ratio, 2.492; 95% CI, 1.190–5.215; P = 0.015). In patients with oral cancer (n = 69), methylated NPY1R and NPY2R were independent prognostic factors for poor DFS, both individually and, even more so, in combination (odds ratio, 3.90; 95% CI, 1.523–9.991; P = 0.005). Similar findings were observed for NPY2R and NPY4R in patients with oropharyngeal cancer (n = 162) (odds ratio, 5.663; 95% CI, 1.507–21.28; P = 0.010).

Simple and rapid LC-MS/MS method for the absolute determination of cetuximab in human serum using an immobilized trypsin

HIGHLIGHTSSerum cetuximab was determined using an LC‐MS/MS method without immunopurification.Fourier transform mass spectrometer selected the surrogate peptide of cetuximab CDR.Immobilized trypsin achieved the rapid digestion of serum cetuximab.Interindividual variability was observed in serum concentration of cetuximab.The serum concentration of cetuximab in LC‐MS/MS was similar to that in ELISA. ABSTRACT Proteomic approaches using liquid chromatography coupled to tandem mass spectrometry (LC‐MS/MS) without an immunopurification technique have not been applied to the determination of serum cetuximab. This study developed a simple and rapid LC‐MS/MS method for the absolute determination of cetuximab in human serum and applied it to clinical settings. Surrogate peptides derived from cetuximab digests were selected using a Fourier transform mass spectrometer. Reduced‐alkylated serum cetuximab without immunopurification was digested for 20 minutes using immobilized trypsin, and the digestion products were purified by solid‐phase extraction. The LC‐MS/MS was run in positive ion multiple reaction monitoring mode. This method was applied to the determination of serum samples in head and neck cancer patients treated with cetuximab. The chromatographic run time was 10 minutes and no peaks interfering with surrogate peptides in serum digestion products were observed. The calibration curve of absolute cetuximab in serum was linear over the concentration range of 4–200 &mgr;g/mL. The lower limit of quantification of cetuximab in human serum was 4 &mgr;g/mL. The intra‐assay and inter‐assay precision and accuracy were less than 13.2% and 88.0–100.7%, respectively. The serum concentration range of cetuximab was 19–140 &mgr;g/mL in patients. The serum cetuximab concentrations in LC‐MS/MS were correlated with those in ELISA (r = 0.899, P < 0.01) and the mean bias was 1.5% in cancer patients. In conclusion, the present simple and rapid method with acceptable analytical performance can be helpful for evaluating the absolute concentration of serum cetuximab in clinical settings.

Survival outcomes after surgical resection of pulmonary metastases of head and neck tumours.

BACKGROUND There is limited information available regarding the benefits and outcomes of resection of pulmonary metastases arising from head and neck cancers. METHODS A retrospective review was performed of 21 patients who underwent resection of pulmonary metastases of primary head and neck malignancies at Hamamatsu University Hospital. Clinical staging, treatment methods, pathological subtype (particularly squamous cell carcinoma), disease-free interval and overall survival were evaluated. RESULTS The 5- and 10-year overall survival rates of the study participants were 67.0 per cent and 55.0 per cent, respectively, as determined by the Kaplan-Meier method. The prognosis for patients with a disease-free interval of less than 24 months was poor compared to those with a disease-free interval of greater than 24 months (p = 0.0234). CONCLUSION Patients with short disease-free intervals, and possibly those who are older than 60 years, should be categorised as having severe disease. However, pulmonary metastases from head and neck malignancies are potentially curable by surgical resection.