Impact of Cochlear Implantation on Canal and Otolith Function.

OBJECTIVE: To quantify the impact of cochlear implantation (CI) on all five vestibular end-organs and on subjective ratings of post-CI dizziness. METHODS: Seventy-two patients undergoing unilateral CI were recruited for the study. All participants completed pre- and post-CI three-dimensional video head-impulse tests (3D vHITs) to assess semicircular-canal (SC) function, air- and bone-conducted (AC and BC) cervical and ocular vestibular-evoked myogenic potentials (cVEMPs and oVEMPs) to assess otolith-function and the dizziness handicap inventory (DHI) to measure self-perceived disability. RESULTS: Nineteen percent of patients reported new or worsened dizziness postsurgery. Post-CI abnormalities (new lesions and significant deteriorations) were seen in the AC cVEMP (48%), AC oVEMP (34%), BC cVEMP (10%), and BC oVEMP (7%); and lateral (L) (17%), posterior (P) (10%), and anterior (A) (13%) SC vHITs. CI surgery was more likely to affect the AC cVEMP compared with the other tests (χ2 test, p < 0.05). Fifty percent of patients reported no dizziness pre- and postsurgery. In the implanted ear, normal pre-CI vHIT gain was preserved in lateral semicircular canal (LSC) (69%), anterior semicircular canal (ASC) (74%), and posterior semicircular canal (PSC) (67%), and normal reflex amplitudes were found in AC cVEMP (25%), AC oVEMP (20%), BC cVEMP (59%), and BC oVEMP (74%). Statistically significant decreases were observed in LSC vHIT gain, AC cVEMP amplitude, and AC oVEMP amplitude postsurgery (p < 0.05). There was a significant moderate positive correlation between change in DHI scores and the summed vestibular deficit postsurgery (r(51) = 0.38, p < 0.05). CONCLUSION: CI can impact tests that assess all five vestibular end-organs and subjective ratings of dizziness. These results support pre and post-surgical vestibular testing and assist preoperative counseling and candidate selection.

Residual adenoid tissue post-curettage: role of nasopharyngoscopy in adenoidectomy.

OBJECTIVE: Curettage adenoidectomy is one of the most common methods of adenoidectomy. This study reports the incidence of residual adenoid tissue after curettage and grades the degree of post-nasal space obstruction using fibre-optic nasopharyngoscopy. METHODS: A retrospective study of 425 consecutive patients undergoing curette adenoidectomy in a 5-year period. RESULTS: Of the 425 patients, 288 (68%) had some residual adenoid tissue evident with nasopharyngoscopy, of which 104 (24%) had significant obstruction (grade 2 or 3). No age or sex difference was found in the likelihood or severity of residual adenoid tissue. CONCLUSIONS: A significant proportion of patients will have residual adenoid tissue following curette adenoidectomy alone. Nasopharyngoscopy permits a more complete resection in a cost-effective, quick and easily performed additional step.

Proteomic profiling of cholangiocarcinoma: diagnostic potential of SELDI-TOF MS in malignant bile duct stricture.

Proteomic techniques promise to improve the diagnosis of cholangiocarcinoma (CC) in both tissue and serum as histological diagnosis and existing serum markers exhibit poor sensitivities. We explored the use of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) to identify potential protein biomarkers of CC. Twenty-two resected CC samples were compared with adjacent noninvolved bile duct tissue. Serum from patients with CC (n=20) was compared with patients with benign disease (n=20), and healthy volunteers (n=25). Samples were analyzed on hydrophobic protein chips via SELDI-TOF MS, and classification models were developed using logistic regression and cross-validation analysis. Univariate analysis revealed 14 individual peaks differentially expressed between CC and bile duct tissue, 4 peaks between CC and benign disease, and 12 peaks between CC and sera of healthy volunteers. The 4,462 mass-to-charge serum peak had superior discriminatory ability to carbohydrate antigen 19.9 (CA19.9) and carcinoembryonic antigen (CEA) (P=.004; receiver operating characteristic [ROC] area under the curve [AUC]=0.76, 0.73, and 0.70, respectively). The training models developed panels of peaks that distinguished CC from bile duct tissue (92.5% sensitivity, 92.3% specificity; ROC AUC=0.96), CC from benign serum (65.0% sensitivity, 70.0% specificity; ROC AUC=0.83), and CC from sera of healthy volunteers (75.0% sensitivity, 100% specificity; ROC AUC=0.92). Serum results were further improved with the inclusion of CA19.9 and CEA (ROC AUC=0.86 and 0.99 for CC vs benign and healthy volunteer serum, respectively). In conclusion, biomarker panels are capable of distinguishing CC from nonmalignant tissue; serum markers have important diagnostic implications for unknown bile duct stricture.

Assessment of HER-2 status in pancreatic adenocarcinoma: correlation of immunohistochemistry, quantitative real-time RT-PCR, and FISH with aneuploidy and survival.

HER-2 is a transmembrane growth factor receptor recognized in overexpression as an independent adverse prognostic factor in several cancers. This study measured HER-2 overexpression in pancreatic adenocarcinoma at the genetic, transcriptional, and translational level. Expression was gauged with regard to stage, grade, and survival. Pancreatic adenocarcinoma samples (n = 30) were analyzed with immunohistochemical labeling for HER-2 protein, Quantitative real-time reverse transcriptase polymerase chain reaction (Q-RT-PCR) measurement of HER-2 mRNA and fluorescence in situ hybridization (FISH) analysis of HER-2 gene expression. HER-2 expression in benign pancreatic lesions (n = 10) provided a control. Five (17%) of the pancreatic adenocarcinomas scored maximal 3+ immunohistochemistry (IHC) labeling, seven (23%) had significantly increased expression of HER-2 mRNA, while only one (3%) exhibited low level HER-2 gene amplification. Ten (33%) tumors demonstrated aneuploidy. In general, concordance between methodologies was poor, but the best agreement was seen between FISH aneuploidy status and Q-RT-PCR mRNA overexpression (80% agreement), followed by IHC and Q-RT-PCR (73% agreement). The least agreement was seen between IHC and FISH aneuploidy status (67% agreement). Tumor stage was positively associated with HER-2 mRNA and protein expression, but tumor grade and other patient characteristics did not reach statistical significance. A poor survival outcome was demonstrated with positive HER-2 status in all three measures of overexpression (Kaplan-Meier log-rank score; P < 0.01 [IHC], P = 0.05 [Q-RT-PCR], P = 0.02 [FISH]). Discordance in expression at the nuclear, cytoplasmic, and cell surface levels highlights the limitations of immunohistochemical evaluation alone and stresses the need for further evaluation of response to anti-HER-2 targeted therapies in tumors displaying overexpression in gene copy, mRNA, and receptor protein.