Human noggin (NOG) is a responsible gene for multiple synostosis syndrome (SYNS1) and proximal symphalangism (SYM1), two conditions that are recently known to be within a wider range of clinical manifestations of stapes ankylosis with symphalangism. This study was performed to determine the range of phenotype caused by NOG mutations, using Japanese patients with various phenotypes including sporadic inherited SYM1, dominantly inherited SYM1, stapes ankylosis with broad thumb and toes (Teunissen and Cremer syndrome). In addition, 33 patients with typical otosclerosis (without symphalangism) were studied. Direct sequencing analysis disclosed three novel mutations of the NOG gene in three SYM1 families. None of the otosclerosis patients without symphalangism had NOG mutations, indicating that NOG mutations may be restrictively found within patients with various skeletal abnormalities. These results together with the literature review indicated that there are no clear genotype-phenotype correlations for NOG mutations. With regard to surgical outcome, most of the patients in these three families with NOG mutations showed remarkable air-bone gap recovery after stapes surgery. Molecular genetic testing is useful to differentiate syndromic stapes ankylosis from otosclerosis, and even mild skeletal anomalies can be a diagnostic indicator of NOG-associated disease.

OBJECTIVE To clarify the mortality rates, causes of death, and contributing clinical factors in Japanese patients with systemic sclerosis (SSc). METHODS A cohort of 405 patients with SSc, who attended our institution during the period 1973 to 2008, was retrospectively analyzed until the end of 2009. Clinical data were obtained from medical records or autopsy reports. RESULTS The 405 patients with SSc consisted of 310 (76.5%) survivors, 86 (21.2%) who died, and 9 who were lost to followup. Diffuse cutaneous SSc and involvement of organs other than the gastrointestinal tract were more frequent in patients who died, and were associated with a worse prognosis according to Kaplan-Meier analysis. Female sex, limited cutaneous SSc, anticentromere antibody (ACA), and overlap with Sjögren's syndrome (SS) were factors favoring a better prognosis, while overlap with myositis contributed to a poor prognosis. The overall 10-year survival rate was 88%. The patients with SSc had a significantly higher mortality than the general population (standardized mortality ratio 2.76), but the patients with ACA or overlapping SS did not. The most common causes of death were unknown ones including sudden death, followed by malignancy and infection. In patients with pulmonary arterial hypertension, sudden death was the most common cause of mortality. CONCLUSION The overall mortality rate of patients with SSc was higher than that of the general population, probably because of poor prognostic factors including organ involvement. These factors should be carefully monitored during followup.

Liver metastases from breast cancer are generally treated with systemic therapy such as chemotherapy or hormonotherapy. However, local treatment options such as resection, radiofrequency ablation (RFA), and radiotherapy can also be considered to treat oligometastases. We report the case of a 45-year-old female treated with stereotactic body radiotherapy (SBRT) after chemotherapy against a solitary liver metastasis from primary breast cancer. A liver metastasis with diameter of 35 mm developed 3.5 years after surgery for primary breast cancer in 2004. Fourteen courses of triweekly docetaxel treatments considerably decreased the metastatic lesion, but there still remained a tiny lesion radiographically. Chemotherapy was stopped because of the side-effects of docetaxel, and then SBRT was selected for additional treatment, aiming at complete cure of metastasis. X-ray irradiation (52.8 Gy/4 fractions) was applied to the remaining metastatic lesion, and magnetic resonance imaging (MRI) showed no evidence of residual tumor 4 months after irradiation. Neither regrowth nor recurrences have been found until now, 24 months after SBRT. SBRT for oligometastases of breast cancer may be one of the possible curative-intent options, being less invasive than surgical resection or RFA.

OBJECTIVE Although docetaxel is active against gastric cancer, Grade 3 or 4 neutropenia occurs in the majority of patients in Japan when administered at 60 mg/m(2) every 3 weeks. To determine a more convenient and tolerable schedule than the tri-weekly schedule, we conducted a dose-escalation study of bi-weekly docetaxel. In this study, we investigated the maximum-tolerated dose and recommended dose. METHODS Patients with advanced gastric cancer who had received prior chemotherapy were enrolled between April 2004 and March 2007. This study was designed to evaluate the escalated dose of docetaxel starting at 35 mg/m(2)(Level 1) given every 2 weeks. The dose was escalated in a stepwise fashion to 40 mg/m(2)(Level 2), 45 mg/m(2)(Level 3) and 50 mg/m(2)(Level 4). RESULTS Fifteen patients completed at least two cycles of the therapy. Three episodes of Grade 3 neutropenia occurred in all patients and Grade 4 neutropenia was observed at Level 4 in six patients. Grade 3 or 4 thrombocytopenia and anemia were not observed. Grade 3 aspartate aminotransferase/alanine aminotransferase elevation (n= 1) and Grade 3 stomatitis (n = 1) were noted at Level 4. There was no other Grade 3 or 4 non-hematologic toxicity. The definition of dose-limiting toxicities of this docetaxel schedule at Level 4 are Grade 4 neutropenia, Grade 3 aspartate aminotransferase/alanine aminotransferase elevation and Grade 3 stomatitis. CONCLUSIONS The maximum-tolerated dose of docetaxel when administrated following the bi-weekly schedule was 50 mg/m(2) and the recommended dose was 45 mg/m(2). Bi-weekly administration of docetaxel may provide a better tolerated and efficacious use in gastric cancer.

Objective. The objective of this study was to demonstrate the prevalence and severity of external auditory canal exostoses in a population of competitive surfers in Japan. The authors used a "surfing index," the product of the period (years) as an active surfer and the frequency (number of surfing days per week), to predict external auditory exostoses formation. Study design. Cross-sectional study. Setting. A total of 5 surfing competitions that were held in Miyazaki, Japan. Materials and Methods. The ear canals of 373 surfers with an average age of 33.1 years (range, 11-80 years) were examined with an otoscope. The severity of exostosis was classified into 4 groups, ranging from grade 0 to 3, according to otoscopic findings. Subjects also completed a questionnaire detailing their surfing habits. Results. There was a 59.8% overall prevalence of exostoses in 373 surfers. The incidences of grade 1, 2, and 3 exostoses were 118 (31.6%), 71 (19.0%), and 34 (9.1%), respectively. The prevalences of grade 2 and 3 exostoses were higher in surfers with a surfing index of more than 20 (P <.0001). Conclusions. The authors determined that a positive association exists between the surfing index and the severity of exostoses. The findings suggest that it is possible to assume the likelihood of exostosis formation from the surfing index, and this may be of help to spread awareness of exostosis among surfers.

To evaluate whether neuro-otological tests have clinical significance in psychiatric patients with nystagmus who have inner ear and/or brain dysfunction, we performed neuro-otological tests on 56 psychiatric patients with nystagmus (38 men, 18 women)(age range 40-97; mean age ± SD 61.6 ± 10.5 years). Patients were classified according to the underlying diseases: schizophrenia (25 cases), organic psychiatric disorders (14 cases), alcoholism (16 cases) and excited mental retardation (1 case). Caloric test results showed a normal response in 30 (75%) cases, right canal paresis (CP) in 4 (10%), left CP in 4 (10%) and bilateral CP in 2 (5%). Therefore, 10 (25%) cases had CP. The results of the eye tracking tests (ETT) were sorted into five categories: 4 (8.2%) cases smooth (normal), 8 (16.3%) slightly saccadic, 28 (57.1%) saccadic, 8 (16.3%) ataxic, and 1 (2%) no tracking ability. Therefore, 45 (91.8%) cases had abnormal ETT results. Pure tone audiometry showed normal hearing in 24 (47.1%) cases, right hearing loss (HL) in 3 (5.8%), left HL in 3 (5.8%) and bilateral HL in 21 (41.2%). Therefore, 27 (52.9%) cases had HL. The patients were classified as organic or functional groups. In ETT there was a significant difference between these two groups. These results indicate that neuro-otological tests with video-oculography are very important not only for neurological or neuro-otological patients with nystagmus, but also for psychiatric patients with nystagmus.

A 29-year-old man and a 36-year-old man developed attacks of acute neuro-Behçet's disease (NB)(right Horner's syndrome and right hemiplegia and dysarthria, respectively) during the course of chronic progressive NB (acute on chronic). Although both patients recovered from acute NB after treatment with infliximab or corticosteroids, they continued to show manifestations of chronic progressive NB. It is suggested that acute NB and chronic progressive NB are different in their pathogenesis.

Many cases of tympanosclerotic stapes fixation are accompanied by fixation or erosion of malleus and/or incus. This status of the ossicular chain is one of the reasons that ossiculoplasty for tympanosclerotic stapes fixation is more difficult than that for otosclerosis. We conducted a retrospective review of seven patients who were operated on for tympanosclerotic stapes fixation between 2002 and 2006. All of the patients had abnormal conditions of the malleus and/or incus and underwent stapedectomy and total ossiculoplasty with hydroxyapatite prosthesis (Apaceram T-7 type), which has a planar-like head portion that contacts a piece of cartilage. Postoperative hearing results were assessed in all seven patients after at least 1 year. The postoperative air-bone gap (ABG) was closed within 10 dB in two of seven patients, and was less than 20 dB in six of seven patients. The mean postoperative ABG was closed within 10 dB at 1 and 2 kHz and less than 20 dB at low frequencies (0.25 and 0.5 Hz). There was almost no hearing improvement at high frequencies (4 and 8 kHz). There were no patients with postoperative sensorineural hearing loss. The present study shows that stapedectomy and total ossiculoplasty with cartilage-connecting hydroxyapatite prosthesis is effective and safe for stapes fixation accompanied by fixation or erosion of the malleus and/or incus.

BACKGROUND: The injection of the biological adhesive fibrin glue is often performed to treat postoperative digestive fistulas. However, it is not always effective especially in case of complex fistulas with large cavities, because the fibrin glue will coagulate before the mixed solutions fill the cavity, creating dead space. We report the results of fibrin glue injection with diluted thrombin solution. METHODS: We studied the tensile strength and coagulation time of the resulting fibrin glue at each dilution of the thrombin solution. Based on in vitro study, 18 patients who had developed postoperative digestive fistula were treated by fibrin glue injection with diluted thrombin solution. RESULTS: In vitro study proved that the dilution of thrombin prolonged the coagulation time of the fibrin glue to more than 1 minute with almost no change to the tensile strength of the glue until a certain dilution was reached. The fistulas of 16 patients were successfully closed. CONCLUSIONS: Our simple method of fibrin glue injection is useful for refractory postoperative digestive fistula, even in cases of complex fistula with large cavities.

An 88-year-old woman, who had undergone distal gastrectomy for Stage IIIA gastric cancer, was diagnosed with recurrent abdominal lymph node metastasis 11 months after surgery. Creatinine clearance of this patient calculated by Cockcroft-Gault method was 44 mL/min and renal function was impaired, so we reduced the administration dosage to 50 mg/day. S-1 was administered for two weeks followed by one week rest. This schedule induced grade 2 anorexia and fatigue after one week administration, so it was converted to one week administration followed by one week rest. By this dosage and administration schedule, a partial response(PR)was continued for about four years without any adverse reaction. This successful case might indicate that it was important for older adult patients with gastric cancer to consider not only appropriate reduction of the dosage but also shortening of S-1 administration.