Joong Ho Ahn

Multicenter phase II study of sunitinib in patients with non-clear cell renal cell carcinoma

BACKGROUND Retrospective and molecular biologic data suggest that sunitinib may be effective in patients with non-clear cell renal cell carcinoma (nccRCC). PATIENTS AND METHODS Eligibility criteria included advanced nccRCC except for collecting duct carcinoma and sarcomatoid carcinoma without identifiable renal cell carcinoma subtypes. Patients were treated with 50 mg/day oral sunitinib for 4 weeks, followed by 2 weeks of rest. The primary end point was overall response rate (RR). RESULTS Thirty-one eligible patients were enrolled. Twenty-four patients (77%) had prior nephrectomy. By Memorial Sloan-Kettering Cancer Center criteria, 8 patients (26%) had poor risk and 14 (45%) had intermediate risk. Twenty-two patients had papillary renal cell carcinoma (RCC), and three had chromophobe RCC. Eleven patients had partial response with a RR of 36% (95% confidence interval (CI) 19% to 52%) and an additional 17 patients (55%) had stable disease. Median duration of response was 12.7 months (95% CI 6.3-19.1 months), and median progression-free survival was 6.4 months (95% CI 4.2-8.6 months). At a median follow-up duration of 18.7 months (95% CI 13.7-23.7 months), 13 patients (42%) had died, resulting in an estimated median survival of 25.6 months (95% CI 8.4-42.9 months). Toxicity profiles were commensurate with prior reports. CONCLUSIONS Sunitinib has promising activity in patients with nccRCC (NCT01219751).BACKGROUND Retrospective and molecular biologic data suggest that sunitinib may be effective in patients with non-clear cell renal cell carcinoma (nccRCC). PATIENTS AND METHODS Eligibility criteria included advanced nccRCC except for collecting duct carcinoma and sarcomatoid carcinoma without identifiable renal cell carcinoma subtypes. Patients were treated with 50 mg/day oral sunitinib for 4 weeks, followed by 2 weeks of rest. The primary end point was overall response rate (RR). RESULTS Thirty-one eligible patients were enrolled. Twenty-four patients (77%) had prior nephrectomy. By Memorial Sloan-Kettering Cancer Center criteria, 8 patients (26%) had poor risk and 14 (45%) had intermediate risk. Twenty-two patients had papillary renal cell carcinoma (RCC), and three had chromophobe RCC. Eleven patients had partial response with a RR of 36% (95% confidence interval (CI) 19% to 52%) and an additional 17 patients (55%) had stable disease. Median duration of response was 12.7 months (95% CI 6.3-19.1 months), and median progression-free survival was 6.4 months (95% CI 4.2-8.6 months). At a median follow-up duration of 18.7 months (95% CI 13.7-23.7 months), 13 patients (42%) had died, resulting in an estimated median survival of 25.6 months (95% CI 8.4-42.9 months). Toxicity profiles were commensurate with prior reports. CONCLUSIONS Sunitinib has promising activity in patients with nccRCC (NCT01219751).

Clinical manifestation and risk factors of children with cleft palate receiving repeated ventilating tube insertions for treatment of recurrent otitis media with effusion

Abstract Conclusion: From this study, we suggest that male gender and complete type of cleft palate contribute to the recurrence of otitis media with effusion (OME) in the patients with cleft palate. Objectives: It is well known that children with cleft palate have a high prevalence of OME due to anatomic dysfunction of the eustachian tube. Our goal was to determine clinical manifestations and risk factors for children with cleft palate who received additional ventilating tube insertions after initial tube insertion during palatoplasty. Methods: We retrospectively reviewed the medical and operation records of 213 patients who received ventilating tube insertion during palatoplasty from January 1993 to June 2006. The single-VT group (n = 140) included patients who had one ventilating tube insertion only, and the repeated-VT group (n = 73) included patients who received ventilating tube insertion repeatedly because of recurring chronic OME. We analyzed age, sex, types of cleft palate, preoperative tympanogram, characteristics of discharge during myringotomy, and duration of first ventilating tube in situ. Results: There were significant differences between the single- and repeated-VT groups in the rate of male patients (43.6 vs 72.6%), the rate of complete cleft palate (30.0 vs 61.6%) and incomplete cleft palate (61.4 vs 26.0%), the rate of preoperative type A tympanogram (30.0 vs 13.7%) and type B tympanogram (57.1 vs 75.3%), the proportion of discharge during myringotomy (72.1 vs 86.3%), and the mean indwelling period of the first ventilating tube (12.7 ± 9.6 vs 10.5 ± 6.5 months). In addition, sex and type of cleft palate were proved to affect the repetition of VT independently. However, when we performed multivariate analysis, only complete type of cleft palate and male gender showed significant differences between single- and repeated-VT groups.

Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging in sudden sensorineural hearing loss: correlations with audiologic and vestibular testing.

Objective: Three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) magnetic resonance imaging (MRI) has recently been applied to the inner ear, but the relationship between 3D-FLAIR findings and audiovestibular function has been unclear in patients with sudden sensorineural hearing loss (SSNHL). We therefore used 3D-FLAIR MRI to investigate vestibular lesions in patients with SSNHL and determined the correlation between these radiologic findings and results of audiovestibular function tests. Study Design: Prospective study. Methods: We enrolled 35 patients who presented with SSNHL from 2008 to 2009. Before treatment, all patients underwent audiovestibular evaluation including pure tone audiometry, electronystagmography, subjective visual vertical, subjective visual horizontal, vestibular evoked myogenic potential, and caloric tests. Pathologic conditions of the inner ears were evaluated by 3D-FLAIR at 3 Tesla, with and without gadolinium enhancement. Results: Of the 35 patients with SSNHL, 12 (34.3%) showed high signals in the affected inner ear on precontrast 3D-FLAIR MRI. Rates of abnormal results on all vestibular function tests were significantly higher for patients with vestibular lesions than those without vestibular lesions on FLAIR (p < 0.05). Vestibular lesions significantly correlated with the presence of vertigo (relative risk, 3.857; 95% confidence interval, 2.039-7.297) and occurrence of vestibular dysfunction (p < 0.05). There was a significant negative correlation between hearing recovery and positive findings on FLAIR (relative risk, −0.475; 95% confidence interval, −0.698 to −0.175; p = 0.004). Conclusion: High signals in the affected inner ear on 3D-FLAIR MRI closely correlate with vestibular dysfunction and poor hearing recovery in patients with SSNHL, especially when the vestibular apparatus is involved.

Evaluation of masking effects on speech perception in patients with unilateral chronic tinnitus using the hearing in noise test.

Objective To verify that tinnitus itself could disturb speech perception and to evaluate the effects of masking noise on speech perception ability in the patients with normal hearing but unilateral chronic tinnitus using the hearing in noise test. Study Design Prospective, nonrandomized study. Materials and Methods Between June 2009 and May 2011, we enrolled 20 patients with normal hearing and subjective unilateral tinnitus that had persisted for more than 12 months, along with 20 healthy controls of the same age. All subjects were evaluated using audiologic examinations, the tinnitus handicap inventory, and the Korean version of the Hearing in Noise Test (K-HINT) to assess characteristics of tinnitus and speech perception ability in various noisy situations. Results Reception threshold for speech (RTS) in a quiet environment and signal-to-noise ratio (SNR) in various conditions of noise were significantly higher in the tinnitus than in the control group, regardless of whether noise came from the front, right, or left (p < 0.05). When the tinnitus group was subdivided according to the site of noise exposure, the mean SNR of the contralateral noise group was −7.9 ± 1.4 dB, which was significantly higher than the ipsilateral noise (−9.1 ± 1.8 dB) or control group (right, −10.0 ± 0.6 dB; left, −10.1 ± 0.5 dB) (p < 0.05). In addition, there was no significant difference between ipsilateral noise and control groups. Conclusion From this study, we showed that tinnitus itself could adversely affect speech perception ability by increasing both RTS and SNR in the tinnitus patients in comparison with healthy controls. In addition, we suggest that proper level of noise on the site of tinnitus might be helpful to increase speech perception in the patients who experience chronic subjective tinnitus.

Gemcitabine-oxaliplatin plus prednisolone is active in patients with castration-resistant prostate cancer for whom docetaxel-based chemotherapy failed.

Background:There has been no previous study on the activity of gemcitabine in combination with oxaliplatin (GemOx) for castration-resistant prostate cancer (CRPC).Methods:The GemOx was preclinically tested for cytotoxic activity in human prostate cancer cell lines. Clinically, patients with CRPC who failed prior docetaxel were treated with gemcitabine 1000 mg m−2 and oxaliplatin 100 mg m−2 intravenously every 2 weeks and prednisolone 5 mg orally twice daily. The primary end point was the prostate-specific antigen (PSA) response rate.Results:The GemOx displayed synergistic effects based on Chou and Talalay analysis. In the phase II study, 33 patients were accrued. The median dose of docetaxel exposure was 518 mg m−2. A total of 270 cycles were administered with a median of eight cycles per patient. A PSA response rate was 55% (95% CI, 38–72) and radiologic response rate was 82% (9 out of 11). With a median follow-up duration of 20.5 months, the median time to PSA progression was 5.8 months (95% CI, 4.4–7.2) and the median overall survival was 17.6 months (95% CI, 12.6–22.6). The most frequently observed grade 3 or 4 toxicities were neutropenia (13%) and thrombocytopenia (13%).Conclusions:The GemOx is active and tolerable in patients with metastatic CRPC after docetaxel failure (NCT 01487720).

Vestibular Function Tests for Vestibular Migraine: Clinical Implication of Video Head Impulse and Caloric Tests

Vestibular migraine (VM) is one of the most common causes of episodic vertigo. We reviewed the results of multiple vestibular function tests in a cohort of VM patients who were diagnosed with VM according to the diagnostic criteria of the Barany Society and the International Headache Society and assessed the efficacy of each for predicting the prognosis in VM patients. A retrospective chart analysis was performed on 81 VM patients at a tertiary care center from June 2014 to July 2015. Patients were assessed by the video head impulse test (vHIT), caloric test, vestibular-evoked myogenic potentials (VEMPs), and sensory organization test (SOT) at the initial visit and then evaluated for symptomatic improvement after 6 months. Complete response (CR) was defined as no need for continued medication, partial response (PR) as improved symptoms but need for continued medication, and no response (NR) as no symptomatic improvement and requiring increased dosage or change in medications. At the initial evaluation, 9 of 81 patients (11%) exhibited abnormal vHIT results, 14 of 73 (19%) exhibited abnormal caloric test results, 25 of 65 (38%) exhibited abnormal SOT results, 8 of 75 (11%) exhibited abnormal cervical VEMP results, and 20 of 75 (27%) exhibited abnormal ocular VEMP results. Six months later, 63 of 81 patients (78%) no longer required medication (CR), while 18 (22%) still required medication, including 7 PR and 11 NR patients. Abnormal vHIT gain and abnormal caloric results were significantly related to the necessity for continued medication at 6-month follow-up (OR = 5.67 and 4.36, respectively). Abnormal vHIT and caloric test results revealed semicircular canal dysfunction in VM patients and predicted prolonged preventive medication requirement. These results suggest that peripheral vestibular abnormalities are closely related to the development of vertigo in VM patients.

Phase II study of pemetrexed in combination with cisplatin in patients with advanced urothelial cancer: the PECULIAR study (KCSG 10-17).

Background:Pemetrexed has shown a favourable response rate of about 30% with minimal toxicity when used as a single agent for treatment of advanced urothelial carcinoma. This phase II study evaluated the efficacy and safety of pemetrexed plus cisplatin in advanced urothelial carcinoma.Methods:This multicentre, single-arm, open-label, phase II clinical trial enrolled patients who had advanced urothelial carcinoma, ECOG PS 0–2, and measurable disease. Pemetrexed 500 mg m−2 with cisplatin 70 mg m−2 on day 1 were administered every 3 weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity.Results:A total of 42 patients were enrolled (median age, 66 years; ECOG 0–1, 100%; visceral metastasis, 54.8%; recurrent disease, 57.1%). Twenty-seven partial responses for an ORR of 64.3% (95% CI, 49.2%–77.0%) were documented. Seven patients had stable disease. Median PFS and OS were 6.9 (95% CI, 6.2–7.6) and 14.4 (95% CI, 10.4–18.4) months, respectively. Grade 3 or 4 neutropenia was observed in 28.6% of patients. No patients experienced febrile neutropenia.Conclusion:The combination of pemetrexed and cisplatin is active, and well tolerated in patients with advanced urothelial cancer as a first-line treatment.

Postoperative results of tympanoplasty with mastoidectomy in elderly patients with chronic otitis media.

Objectives: We evaluated the long-term results of tympanoplasty with mastoidectomy in elderly patients with chronic otitis media (COM). Methods: We included 192 patients with intractable COM who underwent both tympanoplasty and mastoidectomy from the same surgeon between January 2003 and December 2006 and were followed up for more than 3 years. The patients were divided into two groups: An “old COM group” of 83 patients (more than 65 years of age) and a “young COM group” of 109 patients (between 21 and 40 years of age). We compared the preoperative and postoperative levels of hearing, the types of tympanoplasty and mastoidectomy, and the postoperative complications of the two groups. Results: Among the old COM group, 11 patients (13.3%) showed temporary postoperative complaints without serious sequelae. Between the old and young COM groups, there were no significant differences in the rates of associated cholesteatoma, middle ear swab culture results, or type of tympanoplasty, ossiculoplasty, and mastoidectomy. In the comparison of postoperative hearing improvement, both the old and young COM groups showed a significant decrease in air-bone gap, although the old COM group showed a significantly worse preoperative air-bone gap. There were no significant differences in the rates of re-perforation of the tympanic membrane or of reoperation between the two groups. Conclusions: From this study, we conclude that there is no reason to withhold surgery for COM on the assumption that older patients do not have good results or that the procedure is too risky.

Short-term changes in tinnitus pitch related to audiometric shape in sudden sensorineural hearing loss

OBJECTIVE Sudden sensorineural hearing loss (SSNHL) is frequently accompanied by tinnitus. This study investigated the relationships between new-onset tinnitus and audiometric parameters in SSNHL patients. METHODS Sixty-one patients with SSNHL with new-onset tinnitus were enrolled. Changes of tinnitus pitch, and their correlations with the maximum hearing loss frequency (Fmax) and the edge frequency (Fedge) at initial and 1-month follow-up (FU) were analyzed. RESULTS At 1-month FU, tinnitus disappeared in 16 (26%) patients and they also showed hearing normalization. In 36 patients who still showed tonal tinnitus, the mean tinnitus pitch (2.9 kHz) at initial examination, which was close to Fedge (2.7 kHz), increased to a significantly higher frequency (4.6 kHz) at 1-month examination, which was close to Fmax (5.6 kHz). The tinnitus pitch had a more significant correlation with Fedge (r=0.46) than with Fmax (r=0.33) at initial examination and the tinnitus pitch showed a significant correlation only with Fmax (r=0.52) at 1-month examination. CONCLUSIONS Hearing normalization was crucial for the disappearance of tinnitus at 1-month FU. Patients who still had tonal tinnitus at 1-month FU showed the tinnitus pitch closer to the edge frequency (Fedge) at initial examination, and this tinnitus pitch increased to the maximum hearing loss frequency (Fmax) at 1-month FU. This change in tinnitus pitch may give insight about tinnitus generation.

Abnormal CT findings are risk factors for otitis media-related sensorineural hearing loss.

Objectives: Inflammatory processes in chronic otitis media (COM) can damage the inner ear, resulting in sensorineural hearing loss (SNHL). The purpose of this study was to evaluate risk factors by computed tomography (CT) findings for COM-related SNHL in patients with unilateral COM. Design: Records from January 2009 to December 2012 of 231 patients with unilateral COM and a normal contralateral ear were retrospectively evaluated. Bone conduction thresholds were calculated for each ear at 0.5, 1, 2, and 4 kHz. If bone conduction threshold averaged across the four frequencies of the COM ear was 10 dB greater than that of the contralateral ear, the patient was classified under the SNHL group. Temporal bone CT images were analyzed to determine the presence or absence of soft tissue density in the attic (medial/lateral), antrum, oval window niche, and round window niche. Multivariate analysis of sex, age (< 50 years; ≥ 50 years), disease duration (< 20 years; ≥ 20 years), perforation size (small; moderate; large) and the presence of soft tissue density in the attic (medial/lateral), antrum, oval window niche, and round window niche was used to determine the factors related to COM-related SNHL. Results: Of the 231 patients, there were 51 patients (22.1%) in the SNHL group and 180 patients (77.9%) in the non-SNHL group. Multivariate analyses showed that the presence of soft tissue density in the antrum (odds ratio [OR] 3.80; 95% confidence interval [CI] 1.74–8.32; p = 0.001), age ≥ 50 years and more (OR 3.32; 95% CI 1.62–6.81; p = 0.001), disease duration ≥ 20 years (OR 2.80; 95% CI 1.31–6.02; p = 0.008), and the presence of soft tissue density in the round window niche (OR 2.42; 95% CI 1.12–5.21; p = 0.024) were independently related to COM-related SNHL. Conclusions: COM-related SNHL was present in 22% of ears with COM. The presence of soft tissue density in the antrum, determined from temporal bone CT, increased the OR of SNHL to 3.8. Age, disease duration, and the presence of soft tissue density in the round window niche were also independent predicting factors for SNHL. These findings may be used as informative references for patients with COM.