Use of a Woven Endobridge device (WEB) for the treatment of an aneurysmal diverticulum of the transverse sinus causing pulsatile tinnitus.

Pulsatile tinnitus is a symptom with a potentially significant impact on the quality of life of patients.1 In some cases the pulsatile tinnitus is secondary to an arterial, arteriovenous, or a venous condition that can be treated endovascularly.2-5 One of the newly recognized entities that can cause pulsatile tinnitus is the presence of an ipsilateral aneurysmal diverticulum of the transverse sinus. The Woven EndoBridge (WEB) is an intra-aneurysmal flow disruptor for the treatment of broad-based arterial aneurysms with a high safety and effectiveness profile.3 The initial version of the WEB with a dual-layer structure evolved into a single-layer structure in two different versions (WEB SL, a barrel shape, and WEB SLS, a spherical shape).4 The WEB system does not require concomitant antiplatelet therapy, unlike other intraluminal devices such as flow diverters or intracranial stents. We describe a case of pulsatile tinnitus secondary to an aneurysmal diverticulum of the transverse sinus successfully treated with a WEB SL device instead of stent-assisted coiling, therefore alleviating the need for antiplatelets (video 1). The patient had an immediate clinical response with complete and persisting disappearance of her pulsatile tinnitus.neurintsurg;jnis-2023-020981v1/V1F1V1Video 1.

Longitudinal Patient Outcomes in Chronic Dizziness: A Scoping Review.

BACKGROUND: Chronic dizziness can cause significant functional impairment. Outcome measures used in this patient population have not been examined systematically. Consequently, providers lack consensus on the ideal outcome measures to assess the impact of their interventions. OBJECTIVE AND METHODS: We conducted a scoping review to summarize existing literature on outcomes in chronic dizziness (with a minimum of 6 mo of patient follow-up). Among other details, we extracted and analyzed patient demographics, medical condition(s), and the specific outcome measures of each study. RESULTS: Of 19,426 articles meeting the original search terms, 416 met final exclusion after title/abstract and full-text review. Most studies focused on Ménière's disease (75%) and recurrent benign paroxysmal positional vertigo (21%). The most common outcome measures were hearing (62%) and number of attacks by American Academy of Otolaryngology-Head & Neck Surgery criteria (60%). A minority (35%) looked formally at quality-of-life metrics (Dizziness Handicap Index or other). CONCLUSIONS: Ménière's disease and benign paroxysmal positional vertigo are overrepresented in literature on outcome assessment in chronic dizziness. Objective clinical measures are used more frequently than quality-of-life metrics. Future work is needed to identify the optimal outcome measures that reflect new knowledge about the most common causes of chronic dizziness (including persistent postural-perceptual dizziness and vestibular migraine) and consider what is most important to patients.

Vitamin D Supplementation for Benign Paroxysmal Positional Vertigo: A Systematic Review.

OBJECTIVE: Benign paroxysmal positional vertigo (BPPV) is commonly attributed to displaced otoconia. These have been shown to have biomineralization close to that of bone, and vitamin D deficiency has been associated with BPPV. We aim to systematically review the available literature on vitamin D supplementation and BPPV intensity and recurrence in adults. DATABASES REVIEWED: PubMed, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Current Controlled Trials, and ClinicalTrials.gov. METHODS: We systematically reviewed the available literature from 1947 to April 2020. The study protocol was registered in the PROSPERO database (trial registration: CRD42020183195). RESULTS: A total of 179 abstracts were identified and screened by two independent reviewers. Based on inclusion and exclusion criteria, six studies were selected and subjected to a quality assessment. In one randomized clinical trial (RCT), vitamin D supplementation was found to reduce annual recurrence rate of vertigo in patient with BPPV and subnormal serum vitamin D levels compared with placebo (odds ratio, 0.69; 95% confidence interval, 0.54-0.90). Non-RCTs demonstrated the possibility of a null effect in the random effects model (odds ratio, 0.08; 95% confidence interval, 0.00-1.56). The RCT considered as low risk of bias. All of the nonrandomized studies were assessed as serious risk of bias. CONCLUSIONS: The intervention studies identified consistently demonstrated a decrease in BPPV recurrence with supplementation of vitamin D in patients with subnormal vitamin D levels. Although there is a paucity of high-quality studies, the present literature does highlight a role for optimization of vitamin D levels in patients with BPPV.

Characteristics of persistent postural perceptual dizziness patients in a multidisciplinary dizziness clinic.

BACKGROUND: Persistent Postural Perceptual Dizziness (PPPD) is a newly defined condition which was added to the International Classification of Vestibular Disorders in 2017. Little is known about its impact on patients. OBJECTIVE: The goal of this study was to analyze the symptomology, epidemiology and impact of PPPD on patients. METHODS: A retrospective chart review was done to identify patients who attended the Multidisciplinary Dizziness Clinic (MDC) and were diagnosed with PPPD. Responses to demographic questions, health-related quality of life surveys and several well-validated questionnaires commonly used to assess dizziness severity were analyzed. RESULTS: One hundred patients were diagnosed with PPPD between March 2017 and January 2019, of which 80%(80/100) were females. The average Dizziness Handicap Index score was 60.3±19.0. Responses to the Patient Health Questionnaire classified 53 patients (53/99;53.5%) as moderately to severely depressed. Sixty-four patients (64/100;64.0%) were minimally or mildly anxious according to the Generalized Anxiety Disorder scale. The average Vertigo Symptom Scale score was 24.1/60. The average Situational Vertigo Questionnaire score was 2.00. Forty-nine (49/100;49.0%) patients had migraine symptoms according to the Migraine Screen Questionnaire. CONCLUSIONS: In conclusion, patients with PPPD display important handicap and an elevated risk of depression, anxiety and migraines.

Association between obstructive sleep apnea and persistent postural-perceptual dizziness.

BACKGROUND: Obstructive sleep apnea (OSA) has been linked to vestibular dysfunction, but no prior studies have investigated the relationship between Persistent Postural-Perceptual Dizziness (PPPD), a common cause of chronic dizziness, and OSA. OBJECTIVE AND METHODS: We determined the frequency of OSA in an uncontrolled group of PPPD patients from a tertiary dizziness clinic based on polysomnogram (PSG). We then assessed the sensitivity and specificity of common OSA questionnaires in this population. RESULTS: Twenty-five patients with PPPD underwent PSG (mean age 47, 60% female, mean BMI 29.5). A majority, or 56%, of patients were diagnosed with OSA, and in most, the OSA was severe. OSA patients were older (56 years versus 40 years, p = 0.0006) and had higher BMI (32 versus 26, p = 0.0078), but there was no clear gender bias (56% versus 64% female, p = 1.00). The mean sensitivity and specificity of the STOP BANG questionnaire for detecting OSA was 86% and 55%, respectively. Sensitivity and specificity of the Berlin Questionnaire was 79% and 45%, respectively. CONCLUSIONS: The prevalence of OSA was much higher in our small PPPD group than in the general population. Screening questionnaires appear to demonstrate good sensitivity to detect PPPD patients at risk of OSA in this small study. Future studies should confirm these findings and determine whether treatment of OSA improves symptoms in PPPD.

Limited usefulness of routine head and neck CT angiogram in the imaging assessment of dizziness in the emergency department.

OBJECTIVE: To assess the usefulness of head and neck computed tomography angiogram for the investigation of isolated dizziness in the emergency department in detecting significant acute findings leading to a change in management in comparison to non-contrast computed tomography scan of the head. METHODS: Patients presenting with isolated dizziness in the emergency department investigated with non-contrast computed tomography and computed tomography angiogram over the span of 36 months were included. Findings on non-contrast computed tomography were classified as related to the emergency department presentation versus unrelated/no significant abnormality. Similarly, computed tomography angiogram scans were classified as positive or negative posterior circulation findings. RESULTS: One hundred and fifty-three patients were imaged as a result of emergency department presentation with isolated dizziness. Fourteen cases were diagnosed clinically as of central aetiology. Non-contrast computed tomography was positive in three patients, all with central causes with sensitivity 21.4%, specificity 100%, positive predictive value 100%, negative predictive value 92.6% and accuracy 92.8%. Computed tomography angiogram was positive for angiographic posterior circulation abnormalities in five cases, and only two of them had a central cause of dizziness, with sensitivity 14.3%, specificity 97.7%, positive predictive value 40%, negative predictive value 91.46% and accuracy 92.1%. CONCLUSION: Both non-contrast computed tomography and computed tomography angiogram of the head and neck have low diagnostic yield for the detection of central causes of dizziness, However, non-contrast computed tomography has higher sensitivity and positive predictive value than computed tomography angiogram, implying a lack of diagnostic advantage from the routine use of computed tomography angiogram in the emergency department for the investigation of isolated dizziness. Further studies are required to determine the role of computed tomography angiogram in the work-up of isolated dizziness in the emergency department.

Evaluating an inpatient deprescribing initiative at a rural community hospital in Ontario.

BACKGROUND: Deprescribing is an effective means to reduce polypharmacy in elderly patients. However, geriatric day care deprescribing services are challenging to implement in rural regions. In this study, we examined whether a subacute care unit of a rural hospital could deliver a comprehensive and multidisciplinary intervention to promote deprescribing in patients and whether this intervention would succeed in achieving significant and lasting deprescribing results. METHODS: We conducted a cross-sectional analysis of a deprescribing program at a rural hospital in Eastern Ontario, Canada. Participants were 11 patients, aged 65 or older, who were admitted to the hospital's medical/surgical unit or who presented to the emergency department. Clinicians followed a structured, comprehensive and multidisciplinary approach designed to facilitate deprescribing, which concluded with an outcome evaluation at discharge and follow-up phone calls. Outcomes included the frequency and total number of medications successfully removed, reduced, substituted and restarted after discharge and emergency department visits and hospitalizations 6 months before and after the intervention. RESULTS: Of a total 57 deprescribed medications, 38 were eliminated, 8 were switched to a safer alternative, and 11 were dose reduced. Postdischarge deprescribing reversal occurred in only 5 of 57 deprescribed medications. Among the study population, a 59.2% reduction was observed in the combined number of emergency department visits and hospitalizations 6 months after deprescribing. CONCLUSIONS: This feasibility study was successful in showing the potential added value for offering a rehabilitative, subacute care, inpatient, comprehensive and multidisciplinary approach toward patients with complex deprescribing needs. It also showed proof of concept in reducing polypharmacy-induced adverse health outcomes. Can Pharm J (Ott) 2020:153:xx-xx.

Improving urinary catheterisation practices in a rural hospital in Ontario.

INTRODUCTION: A urinary catheter constitutes a one-point patient restraint, can induce deconditioning and may lead to patient mortality. An audit performed at Winchester District Memorial Hospital revealed that 20% of patients had a urinary catheter, of whom 31% did not meet the criteria for catheterisation. The main objective of this study was to use the Influencer Change Model and the Choosing Wisely Canada toolkit to create a bundle of interventions that would reduce the unnecessary use of urinary catheters in hospitalised patients. METHODS: In a rural teaching hospital, a time-series quasi-experiment was employed to decrease inappropriate use of urinary catheters. Both the Choosing Wisely Canada toolkit for appropriate use of urinary catheters and the Influencer change management approach were used to create effective interventions. RESULTS: This study revealed that there was no improvement in appropriate urinary catheter use during Plan-Do-Study-Act (PDSA) cycle 1. There was gradual improvement during PDSA cycle 2, with the percentage of inappropriate urinary catheter use dropping from an initial 31% before any interventions to less than 5% by the end of this study. DISCUSSION/CONCLUSION: This study aimed to reduce the inappropriate use of urinary catheters in a rural hospital with limited resources. The findings indicate that by using a change model, such as the Influencer Change Model, it is possible to promote better patient care through empowering healthcare staff to implement accepted protocols more stringently and thereby to decrease the inappropriate use of urinary catheters to 0%.

A retrospective analysis of two tertiary care dizziness clinics: a multidisciplinary chronic dizziness clinic and an acute dizziness clinic.

BACKGROUND: Vertigo remains a diagnostic challenge for primary care, emergency, and specialist physicians. Multidisciplinary clinics are increasingly being employed to diagnose and manage patients with dizziness. We describe, for the first time in Canada, the clinical characteristics of patients presenting with chronic and acute dizziness to both a multidisciplinary chronic dizziness clinic (MDC) and a rapid access dizziness (RAD) clinic at The Ottawa Hospital (TOH). METHODS: We performed a retrospective review of all patients presenting to the MDC and RAD clinics at TOH from July 2015 to August 2017. RESULTS: Overall, 211 patients (median age: 61 years old) presented to the RAD clinic and 292 patients (median age: 55 years old) presented to the MDC. In the RAD clinic, 63% of patients had peripheral dizziness, of which 55% had BPPV, and only one patient had functional dizziness. Interestingly, only 25% of RAD diagnoses were concordant with emergency department diagnoses; moreover, only 33% of RAD patients had HiNTS completed, while 44% had CT scans, of which only one scan had an abnormal finding. Prior to assessment, all patients in the MDC had an unclear cause of dizziness. 28% of patients had vestibular dizziness and 21% had functional dizziness, of which 43% had persistent postural perceptual dizziness. Moreover, 12% of patients with functional dizziness also suffered from comorbid severe anxiety and depression. CONCLUSIONS: Dizziness is a heterogeneous disorder that necessitates multidisciplinary care, and clinics targeting both the acute and chronic setting can improve diagnostic accuracy, ensure appropriate diagnostic testing, and facilitate effective care plans for patients with dizziness.

Dizziness at a Canadian tertiary care hospital: a cost-of-illness study.

BACKGROUND: In the Canadian health care system, determining overall costs associated with a particular diagnostic subgroup of patients, in this case dizzy patients, is the first step in the process of determining where costs could be saved without compromising patient care. This study is the first Canadian study that evaluates these costs at a tertiary care hospital and will allow for the extrapolation of cost data for other similar academic health science centers, regional health initiatives, and provincial healthcare planning structures. METHODS: We conducted a retrospective cohort study of patients of any age presenting to The Ottawa Hospital (TOH), a tertiary care hospital, between January 1st, 2009 and December 31st, 2014 with a main diagnosis of dizziness or dizziness-related disease. De-identified patient information was acquired through TOH Data Warehouse and included a patient's sex, age, arrival and departure dates, Elixhauser co-morbidity score, location of presentation (emergency department or admitted inpatient) presenting complaint, final diagnosis code, any procedure codes linked to their care, and the direct and indirect hospital costs linked with any admission. We derived the mean hospital costs and 95% confidence interval for each diagnosis. We obtained the number of patients who were diagnosed with dizziness within Ontario in year 2015-16 from Canadian Institute for Health Information (CIHI). A simple frequency multiplication was performed to estimate the total cost burden for Ontario based on the cost estimate for the same year obtained from TOH. Cost data were presented in 2017 Canadian dollars. RESULTS: The average total hospital cost per patient with dizziness for the entire cohort is $450 (SD = $1334), with ED only patients costing $359 (SD = $214). The total estimated hospital cost burden of dizziness in Ontario is $31,202,000 (95% CI $29,559,000 - 32,844,000). CONCLUSIONS: The estimated annual costs of emergency department ambulatory and inpatient dizziness in Ontario was calculated to be approximately 31 million dollars per year. This is the first step in identifying potential areas for cost savings to aid local and provincial policy-makers in allocation of health care spending.

Novel Use of Portable Audiometry to Track Hearing Fluctuations in Menière's Disease: A Pilot Study.

INTRODUCTION: Menière's Disease (MD) is a disorder of the inner ear consisting of episodic attacks of vertigo associated with aural fullness, tinnitus, and fluctuating hearing loss. Hearing levels in MD can often fluctuate over time, and may eventually decline permanently in a step-wise fashion. There are no current studies examining daily hearing fluctuations for prolonged periods in patients with MD. Portable audiometry has the potential to allow the patient to monitor their hearing on a daily basis without attending a center for formal audiology. The objective of this pilot study was to assess feasibility of using iPad-based audiometry on a daily basis to capture hearing fluctuations in a small sample of adult patients with active MD. METHODS: We recruited five patients with active MD as defined by current diagnostic criteria (International Classification of Vestibular Disease 2015). "Active" MD was defined as the patient having had at least one typical Menière's episode within the last 4 weeks. Patients were trained on how to use the portable audiometer and asked to perform at least daily audiograms for 3 months. Patients were asked to manually track vertigo attacks in a diary. Qualitative feedback was obtained from each patient at each monthly visit. For each patient, individual pure tone thresholds at each frequency and pure-tone averages (PTA) were analyzed for maximum and minimum values and interquartile ranges. RESULTS: There were four women and one man, with an average age of 49.8 years. Duration of MD ranged from 4 months to 5 years. None of the patients experienced any technical difficulties performing the testing at home. The average duration of each test was 4.2 minutes, with the longest test taking 19.2 minutes. Patients completed between 45 and 102 tests, with an average of 72. The interquartile range for the PTA ranged from 2.5 to 25 dB for affected ears, and 0 to 6.25 dB for unaffected ears with maximums ranging from 5 to 35 dB in affected ears, and 0 to 10 dB in unaffected ears. CONCLUSIONS: Daily portable audiometry is feasible in patients with MD. Future studies are planned to further analyze hearing fluctuations in MD with respect to frequencies affected, relationship to vertigo attacks, and response to treatments. Understanding hearing fluctuations in MD may aid refinement of diagnostic criteria and improve prognostication for long-term hearing loss, with a goal of informing treatments that might improve final hearing outcome.

Usage of the HINTS exam and neuroimaging in the assessment of peripheral vertigo in the emergency department.

BACKGROUND: Dizziness is a common presenting symptom in the emergency department (ED). The HINTS exam, a battery of bedside clinical tests, has been shown to have greater sensitivity than neuroimaging in ruling out stroke in patients presenting with acute vertigo. The present study sought to assess practice patterns in the assessment of patients in the ED with peripherally-originating vertigo with respect to utilization of HINTS and neuroimaging. METHODS: A retrospective cohort study was performed using data pertaining to 500 randomly selected ED visits at a tertiary care centre with a final diagnostic code related to peripherally-originating vertigo between January 1, 2010 - December 31, 2014. RESULTS: A total of 380 patients met inclusion criteria. Of patients presenting to the ED with dizziness and vertigo and a final diagnosis of non-central vertigo, 139 (36.6%) received neuroimaging in the form of CT, CT angiography, or MRI. Of patients who did not undergo neuroimaging, 17 (7.1%) had a bedside HINTS exam performed. Almost half (44%) of documented HINTS interpretations consisted of the ambiguous usage of "HINTS negative" as opposed to the terminology suggested in the literature ("HINTS central" or "HINTS peripheral"). CONCLUSIONS: In this single-centre retrospective review, we have demonstrated that the HINTS exam is under-utilized in the ED as compared to neuroimaging in the assessment of patients with peripheral vertigo. This finding suggests that there is room for improvement in ED physicians' application and interpretation of the HINTS exam.

Improving access to otolaryngology-head and neck surgery expert advice through eConsultations.

OBJECTIVES/HYPOTHESIS: Prolonged wait times have become common. Electronic consultations (eConsults) have been shown in previous studies to reduce unnecessary face-to-face consultations to specialists, but no prior study has investigated the feasibility or efficacy of eConsults in an otolaryngology-head and neck surgery (OTO-HNS) practice. STUDY DESIGN: Prospective observational study. METHODS: The Champlain BASE eConsult system is a secure web portal allowing primary care physicians (PCPs) to communicate asynchronously with specialists about a patient, without requiring a formal face-to-face consult. The data from all eConsults sent through this portal to OTO-HNS practices between July 2011 and January 2015 were collected and analyzed. RESULTS: Response time was rapid; over 40% of eConsults received a response within 24 hours, and nearly all eConsults were answered within 7 calendar days. The median response time was nearly 29 times faster than traditional face-to-face consultation. Unnecessary face-to-face referrals were avoided in 33.4% of all eConsults, and in nearly 50% of cases where the PCP initially planned a formal referral. PCPs reported adopting a new or additional course of action over 50% of the time following an eConsult. Eighty-eight percent of PCPs reported the service to be valuable for their patients, and 92% found it valuable for themselves. eConsults require only a limited time commitment from specialists, with over 75% taking less than 10 minutes to complete. CONCLUSIONS: eConsultation is a cost-effective system that can lead to decreased wait times, improved communication between PCPs and otolaryngologists, and help guide the development of targeted continuing professional development modules for PCPs. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:350-355, 2018.

Autoimmune arthritis in Ménière's disease: A systematic review of the literature.

INTRODUCTION: Successful management of patients with Ménière's disease (MD) involves understanding the pathophysiology of the disease and its comorbidities. The role of autoimmune diseases (AD) in MD remains unclear. The aim of this study was to further investigate the association between MD and AD. Specific goals were to characterize the prevalence, distribution, clinical and laboratory findings, and outcomes of autoimmune arthritis (AA) in MD. EVIDENCE REVIEW: This systematic review was conducted according to PRISMA guidelines. Articles were identified through searches of MEDLINE, and EMBASE, as well as manual reviews of references, from 1947 to May 2017. We performed a systematic review of randomized-controlled trials (RCTs) and non-RCTs of cases of AA in MD. Due to the heterogeneity of the study methods and measures, a meta-analysis was not possible and a qualitative synthesis of the literature results was performed. The study protocol was registered with PROSPERO database (Trial Registration: CRD42017070516). FINDINGS: A total of 237 abstracts were identified and screened by two independent reviewers. Based on inclusion and exclusion criteria, nine studies were selected and subjected to a quality assessment. This quality control measure yielded eight studies for analysis in the systematic review. The prevalence of AA was higher in MD (1.0-10.0%) as compared to the general population (0-1.1%), and noted to be higher in patients with familial MD as compared to sporadic MD (16.9% vs 4.5%, p = 0.002). There was no evidence to suggest a difference in immunologic profiles or selected treatment regimens. The most commonly reported AA in patients with MD was rheumatoid arthritis with a mean point prevalence of 4.3%. Many studies did not standardize their diagnostic criteria and did not measure clinically meaningful outcomes. CONCLUSIONS: There is a low level of evidence because of the lack of RCTs and original prospective studies. However, in this systematic review, we have identified the latest point prevalence data on AA in MD, indicating AA to be more prevalent within the MD population. RCTs treating MD as a local AD will enhance our understanding of the disease, and potentially change the way we manage MD.

Prospective clinical trial of gelatin-thrombin matrix as first line treatment of posterior epistaxis.

OBJECTIVES/HYPOTHESIS: To evaluate the effectiveness of gelatin-thrombin matrix for first line treatment of posterior epistaxis. Secondarily, we evaluated discomfort during treatment and the cost savings of treatment with gelatin-thrombin matrix compared to posterior packing, endoscopic, or endovascular treatment at our institution. STUDY DESIGN: Prospective pilot, nonblinded, noncontrolled registered clinical trial (NCT01098578). METHODS: Twenty patients with posterior epistaxis were enrolled into this study. Gelatin-thrombin matrix was used for posterior epistaxis treatment with simultaneous ipsilateral choanal occlusion. Patients were discharged within 2 hours of being successfully treated. A visual analog scale (range 0-10) was used to assess treatment discomfort. Patients were evaluated in clinic 5 and 30 days after treatment to assess for intranasal complications and recurrent epistaxis. RESULTS: Gelatin-thrombin matrix successfully treated epistaxis in 80% of the patients. The procedure was associated with a mean discomfort of 3.6 (range 0-9.7). The institutional per case cost of treatment of patients with posterior epistaxis with gelatin-thrombin matrix is 80.3%, 87.4%, and 89.4% less than with endoscopic surgery, posterior packing, or embolization, respectively. There were no complications. CONCLUSION: This pilot study demonstrated that gelatin-thrombin matrix is a safe and both a clinically effective and cost-saving means of treating posterior epistaxis. In this study, its use is associated with a low level of discomfort. This treatment method may improve the quality of care for patients with posterior epistaxis.

Management of the radial forearm free flap donor site using a topically applied tissue expansion device.

BACKGROUND: The purpose of this study was to prospectively assess clinical outcomes in patients undergoing a new method of donor site management for radial forearm free flaps. METHODS: 177 patients underwent reconstruction of ablative defects of the head and neck using a radial forearm free-flap. All patients had topical tissue expansion tapes applied to their forearms preoperatively. Closure rates, healing time and complications associated with the technique were assessed. RESULTS: Ninety-five percent of patients had their donor sites closed primarily with a locally harvested full thickness skin graft. Complications related to the tissue expansion device included a loss of device adhesion (19.3%) requiring reapplication and minor pruritic reactions (4.1%). CONCLUSIONS: This system of donor site management has resulted in a significant reduction in the requirement of a split thickness skin graft for coverage of the donor site in a radial forearm free flap without any significant economic cost or patient morbidity.

Polymorphisms of the NER pathway genes, ERCC1 and XPD are associated with esophageal adenocarcinoma risk.

PURPOSE: Functional variation in DNA repair capacity through single nucleotide polymorphisms (SNPs) of key repair genes is associated with a higher risk of developing various types of cancer. Studies have focused on the nucleotide excision repair (NER) and base excision repair (BER) pathways. We investigated whether variant alleles in seven SNPs within these pathways increased the risk of esophageal adenocarcinoma. METHODS: DNA was extracted from prospectively collected blood specimens. The samples were genotyped for SNPs in NER genes (XPD Lys751Gln, XPD Asp312Asn, ERCC1 8092C/A, and ERCC1 118C/T), and BER genes (XRCC1 Arg399Gln, APE1 Asp148Glu, and hOGG1 Ser326Cys). The presence of variant alleles was correlated with risk of esophageal adenocarcinoma both individually and jointly. RESULTS: Variant alleles in NER SNPs XPD Lys751Gln (AOR = 1.50, 95% CI 1.1-2.0), ERCC1 8092 C/A (AOR = 1.44, 95% CI 1.1-1.9), and ERCC1 118C/T (AOR = 1.42, 95% CI 1.0-1.9) were individually associated with esophageal adenocarcinoma risk. An increasing number of variant alleles in NER SNPs showed a significant trend with esophageal adenocarcinoma risk (p = 0.007). CONCLUSIONS: The presence of variant alleles in NER genes increases risk of esophageal adenocarcinoma. There is evidence of an additive role for SNPs along a common DNA repair pathway. Future larger studies of esophageal adenocarcinoma etiology should evaluate entire biological pathways.

Genetic polymorphisms and head and neck cancer outcomes: a review.

Head and neck cancer (HNC) patients have variable prognoses even within the same clinical stage and while receiving similar treatments. The number of studies of genetic polymorphisms as prognostic factors of HNC outcomes is growing. Candidate polymorphisms have been evaluated in DNA repair, cell cycle, xenobiotic metabolism, and growth factor pathways. Polymorphisms of XRCC1, FGFR, and CCND1 have been consistently associated with HNC survival in at least two studies, whereas most of the other polymorphisms have either conflicting data or were from single studies. Heterogeneity and lack of description of patient populations and lack of accounting for multiple comparisons were common problems in a significant proportion of studies. Despite a large number of exploratory studies, large replication studies in well-characterized HNC populations are warranted.