Intravitreal bevacizumab treatment reduces ocular blood flow in retinopathy of prematurity: a four-case report.

PURPOSE: To evaluate the relationship between ocular blood flow, expressed as mean blur rate (MBR) by laser speckle flowgraphy, and intravitreal bevacizumab (IVB) therapy in neonates with retinopathy of prematurity (ROP). METHODS: This was a case series study of 4 neonates with ROP under sedation before and after IVB and evaluated 8 eyes, in which the circulation could be measured three times consecutively. We performed optic nerve head blood flow measurement and fluorescein angiography (FA) before and 1 week after treatment. Blood flow was analyzed separately for MBR-A (mean of all values), MBR-V (vessel mean), and MBR-T (tissue mean). Comparisons between the MBR (-A, -V, -T), body weight, and other systemic and ocular parameters before and after treatment were performed using a paired t test. RESULTS: The MBR values after IVB were lower than the pre-treatment values in all cases. All eyes showed leakage at neovascularization on FA before treatment. Although leakage improved 1 week after treatment, the neovascularization did not completely regress. CONCLUSIONS: IVB improves vein dilation and artery tortuosity, while reducing ocular blood flow in neonates with ROP. We suggest that neovascularization might not be involved in reducing ocular blood flow in the early stage of IVB treatment.

Multicenter phase I/II study of chemoradiotherapy with high-dose CDDP for head and neck squamous cell carcinoma in Japan.

OBJECTIVE: Recent data indicated that concurrent chemoradiotherapy (CCRT) using high dose cisplatin (CDDP) is the most useful treatment for advanced head and neck squamous cell carcinoma (SCC). Regarding the dose of CDDP, 100mg/m2 is most recommended in Western countries. However, in terms of a balance of efficacy and adverse events, appropriate dose of cytotoxic drugs such as CDDP may be different among the different ethnic groups. In this multicenter phase I/II study, we aimed to identify the optimal dose of CDDP in CCRT for patients with advanced head and neck SCC in the Japanese. METHODS: Patients were eligible for inclusion if they had head and neck SCC that was treated with radical CCRT comprising whole-neck irradiation of the primary lesion and level II-IV lymph nodes on both sides. For the phase I study, a CDDP dose was 70mg/m2 for level 0, 80mg/m2 for level 1, and 100mg/m2 for level 2. Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) were examined by phase I trial, by which CDDP dose for phase II was determined. The primary endpoint for the phase II was CCRT completion rate, and the secondary endpoint was full-dose-CCRT completion rate, the percentage of patients receiving a total CDDP dose of ≥200mg/m2, response rate, and incidences of adverse events. RESULTS: A CDDP dose of 100mg/m2 was the MTD for phase I, and the recommended dose for phase II was 80 mg/m2. Forty-seven patients were evaluated in the phase II trial. CCRT completion rate, full-dose-CCRT rate, and the percentage of patients receiving a total CDDP dose of ≥200mg/m2, were 93.6%, 78.7%, and 93.6%, respectively. One patient (2.1%) developed grade 2 renal dysfunction, and no patient developed febrile neutropenia or a grade 4 adverse event. CONCLUSION: The present phase I study indicated that a CDDP dose of 80mg/m2 is the optimal dose in terms of safety. The phase II study revealed that CCRT completion rate, response rate, and rates of adverse events were not inferior for a CDDP dose of 80mg/m2 as compared with a dose of 100mg/m2, and a dose of 80mg/m2 is therefore recommended in CCRT for the Japanese. This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; identification No. UMIN000010369).

[Concurrent chemoradiotherapy with either CDDP or CDGP, plus 5-FU for squamous cell carcinoma of the oropharynx and hypopharynx].

Clinical outcomes of 53 patients with oropharyngeal and hypopharyngeal squamous cell carcinoma, treated from January, 2000 to December, 2008 by concurrent chemoradiotherapy of either CDDP or CDGP, plus 5-FU were investigated. Patients were treated with either CDDP (70 mg/m2) or CDGP (100 mg/m2) on day 1 of the chemotherapy regime, with 5-FU (700 mg/m2/day) as a continuous infusion for 5 days. Each regimen was administered as two courses in the first and final weeks of radiotherapy. Radiotherapy was administered at a daily dose of 2 Gy for five days a week, with patients receiving a total of 70 Gy by the end of seven weeks. The primary cancer was located in the oropharynx and hypopharynx in 21 and 32 patients, respectively. Twenty-six patients (49.1%) had stage IVA disease and 10 patients (18.9%) had overall stage I to II disease. Acute adverse events such as pharyngeal mucositis and leucopenia occurred in 49.1% and 43.4% of patients, respectively, and second round chemotherapy was not commenced in 56.6% of patients (n=30) due to significant adverse events. Mean weight loss following treatment was 4.1 kg. After a median follow-up of 30.0 months, 3-year overall survival was 53.0% for advanced carcinoma of the oropharynx and hypopharynx. Five-year overall survival was 46.4%. Patients receiving two courses of chemotherapy had an improved 5-year survival compared to patients receiving one course (67.0% vs 32.8%). Results indicate a significant benefit from two courses of chemotherapy. As such, minimizing the incidence of adverse effects and thereby reducing treatment discontinuation will likely improve overall treatment outcomes.

Tremulous arytenoid movements predict severity of glottic stenosis in multiple system atrophy.

To determine whether tremulous arytenoid movements predict the severity of glottic stenosis in patients with multiple system atrophy (MSA), 28 MSA patients and 14 age-matched controls underwent fiberoptic laryngoscopy with video monitoring during wakefulness and under anesthesia induced by intravenous injection of propofol. Presence or absence of tremulous arytenoid movements was recorded during wakefulness. The ratio of glottic stenosis (%), which represents the extent of airway narrowing under anesthesia, was obtained by measuring the inspiratory glottic angle during wakefulness and under anesthesia. The median ratio of glottic stenosis was significantly higher in patients with MSA (57.5%) than in control subjects (0.5%). Tremulous arytenoid movements were characterized by shaking movements of the arytenoid region including the vocal folds, which are most apparent in the arytenoid cartilage. In this study, tremulous arytenoid movements were observed in 18 (64.2%) of 28 patients with MSA, who displayed a significantly higher median ratio of glottic stenosis (71.2%) than other patients (34.9%). None of the control subjects exhibited tremulous arytenoid movements. A clear correlation existed between the ratio of glottic stenosis and disease duration. Our observations indicate that tremulous arytenoid movements are a marker of the severity of glottic stenosis, which confers an increased risk of upper airway obstruction in patients with MSA.

[Clinical evaluation of patients with pyriform sinus fistula].

Thirteen patients with pyriform sinus fistula treated surgically at our department were clinically evaluated. Twelve (92%) fistulae occurred in the left pyriform sinus, and one (8%) in the right. There were a mean of 4 infectious episodes before the final diagnosis. The median age at the first infection was 5 years, and the median age at surgery was 13 years, although there were 2 elderly patients (over 60 years old) in this series. Association with pharyngeal foreign body was suspected in the case with onset at 81 years of age. There was a history of previous surgery for cervical disease in 54% of the patients. The final diagnosis was based on delineation of the fistula by hypopharyngography, although coronal section of CT and MRI were also useful for understanding the morphopathology. The surgical procedure consisted of identification and staining of the fistula under direct hypopharyngoscopy, followed by identification and extirpation of the fistula until the distal end via a cervical approach. There was no recurrence of infections, although resection of the thyroid gland and identification of the recurrent laryngeal nerve were not always performed. The most important surgical principle is considered to be complete disconnection of the lesion from the hypopharynx, and complete identification and extirpation of the fistula by the procedure used at our department is considered to be a useful surgical strategy.