Incidence of long-term ipsilateral and contralateral ototoxicity following radiotherapy for nasopharyngeal carcinoma

Objective

To characterize the long-term adverse effects of radiotherapy on the ears in patients with nasopharyngeal carcinoma (NPC), we investigated ipsilateral and contralateral ototoxicities in the external, middle, and inner ear.

Methods

The records of 48 ears in 24 radiotherapy-treated NPC patients were retrospectively analyzed. Radiotherapy doses varied between 60 and 70 Gy in 2-Gy fractions at 5 fractions/week. Ototoxicities were identified by otoscope and pure-tone audiograms conducted at 2-3 month intervals for ≥12 months. The relationship between radiation dosage and sensorineural threshold deterioration was statistically compared using the Mann-Whitney U-test.

Results

Post-radiotherapy, 50% of all ears (3 of 6) that developed severe otitis externa were on the contralateral side. There was a post-radiotherapy increase in contralateral otitis media with effusion (OME) (1-7 ears), but a decrease in ipsilateral cases (16-12 ears), with 2 ears on either side subsequently developing chronic otitis media (COM). All ears that showed sensorineural hearing loss (SNHL) before radiotherapy exhibited a further threshold deterioration of more than 15 dB. No statistically significant difference (p = 0.086) in average radiation dose was seen between ears with sensorineural threshold deterioration (50.0 Gy) and those without (48.2 Gy).

Conclusion

Long-term ototoxicity following radiotherapy for NPC can occur in either the ipsilateral or contralateral ears. Pathophysiology varies between and within each side. The post-therapy increase in OME on the contralateral side was thought to be due to radiotherapy-induced Eustachian tube damage, and the sensorineural threshold deterioration in at least 4 ears was thought to be due to chronic cochlea damage secondary to COM.     

Intramedullary primitive neuroectodermal tumor presenting with rapidly-progressive cauda equina syndrome

A 39-year-old male presented with gait disturbances with rapid deterioration for 2 weeks. Neurological examination found paraparesis, sensory loss in the L1-S5 dermatomes, and vesicorectal dysfunction. Magnetic resonance (MR) imaging revealed a fusiform intramedullary tumor at T12-L1 levels with heterogeneous enhancement. The patient underwent microsurgical tumor resection. A myelotomy exposed a highly vascular tumor that was subtotally resected. Histological examination demonstrated hypercellular tumor accompanied by significant cell atypism and mitotic figures. Immunohistochemical staining was positive for glial fibrillary acidic protein, S-100 protein, synaptophysin, and INI-1, consistent with primitive neuroectodermal tumor (PNET). Postoperatively, the patient underwent irradiation to the whole craniospinal axis. He experienced local recurrence 7 months after surgery. MR imaging performed at 10 months revealed holocord progression and intracranial dissemination. The patient died 13 months after the onset of the disease. PNET should be considered in the differential diagnosis of an intramedullary spinal cord tumor.     

Genetic Prognostic Index Influences Patient Outcome for Node-Positive Breast Cancer

Purpose To establish a novel genetic prognostic index among node-positive breast cancer patients. Methods Using a cDNA microarray, the gene expression profiles of 20 primary breast cancers that had metastasis to four or more axillary lymph nodes were examined. Ten patients survived disease-free for more than 5 years (5S), while ten patients died of breast cancer within 5 years of surgery (5D). Results A set of genes characterizing each group was identified. Sixteen genes were underexpressed in 5D compared to 5S, and 15 genes were underexpressed in 5S in comparison to 5D. The prognostic index (PI) was established, which could predict the postoperative outcome with five genes that were commonly underexpressed in the 5D group; these genes encoded granulin (GRN), heat shock 90 kDa protein 1 beta (HSPCB), large tumor suppressor homolog 1 (LATS1), valosin-containing protein (VCP), and LIM-and-SH3 protein1 (LASP1). Conclusion These five genes might play an important role in deciding the behavior of node-positive breast cancer. The PI system could thus predict the prognosis of node-positive breast cancer, and might therefore be able to provide valuable information for the prognosis of breast cancer patients.     

Benign pleomorphic astrocytoma in the hypothalamus--case report

A 41-year-old woman presented with an unusual case of benign astrocytoma with marked pleomorphism manifesting as consciousness disturbance due to intraventricular hemorrhage. Magnetic resonance imaging revealed a well-enhanced hypothalamic mass protruding into the third ventricle. Despite partial resection of the tumor without additional therapy, there have been no signs of tumor regrowth for 6 years. The histological findings revealed solid proliferation of tumor cells with marked pleomorphism, contrary to the benign clinical course. However, no mitosis, necrosis, or endothelial proliferation were found and the MIB-1 index was less than 0.5%. Immunohistochemical staining indicated the glial origin of the tumor. The tumor was similar to pleomorphic xanthoastrocytoma, but the histological findings were not exactly identical, indicating a new histological entity.     

Nerve fiber layer measurement using scanning laser polarimetry with fixed corneal compensator in normal cynomolgus monkey eyes

PURPOSE: The purpose of this study was to examine retinal nerve fiber layer thickness in normal cynomolgus monkeys using a scanning laser polarimeter with a fixed corneal compensator (GDx FCC), and to clarify the reproducibility and symmetries (right-left differences) between both eyes for the GDx parameters. METHODS: GDx parameters were measured in 36 normal eyes of 18 cynomolgus monkeys aged 4.0-5.5 years. The retardation values (thickness parameters) at peripapillary and macular areas obtained from the GDx FCC were measured and calculated thickness, ratio, and modulation parameters in the superior and inferior quadrants. Mean and standard deviation (SD), coefficient of variation (CV), and binocular differences were obtained for each parameter from three independent measurements made during a 1-week period. Correlation between both eyes in macular retardation and baseline values, which indicated the combined minimum retardation values for the nasal and temporal quadrants, and between macular retardation and baseline values were analyzed. RESULTS: The intraocular pressure values (mean +/- SD, n = 18) obtained for the right and left eyes were 20.7 +/- 3.8 and 20.0 +/- 3.2 mm Hg, respectively (no significant differences in both eyes). No significant differences between right and left eyes were detected for any GDx parameters. All parameters showed small right-left differences. The CVs (SD/mean x 100) for all parameters were less than 10%. Highly significant correlations were seen between bilateral eyes for macular retardation (r = 0.936, p < 0.0001) or baseline values (r = 0.946, p < 0.0001). A significant correlation (r = 0.883, p < 0.0001) was also seen between macular retardation and baseline values. CONCLUSIONS: Considering individual differences in corneal birefringence, GDx parameters obtained from a GDx FCC may be useful for the objective evaluation of time-related changes in individual eyes or for binocular comparisons in cynomolgus monkeys.