Endoscopic Endonasal Approach for Resection of a Recurrent Craniopharyngioma: Techniques to Maximize Surgical Exposure and Extent of Resection.

Craniopharyngiomas are challenging tumors of the central nervous system that originate from epithelial remnants of the Rathke pouch.1-3 Despite maximum safe resection, these tumors present a high tendency to recur (∼20%-40%), even after apparent gross total resection.1,2 The management of recurrent craniopharyngiomas is more challenging, associated with a higher risk of permanent morbidity and complications.1,3 The endoscopic endonasal approach is an option for recurrent tumors, especially in the presence of a previous transcranial approach.1,3-7 In Video 1, we present a case of a 63-year-old man with a recurrent craniopharyngioma with a 2-month history of visual decline, confusion, impaired memory, and episodes of urinary incontinence. On physical examination, he presented slow speech, word-finding difficulties, and left homonymous hemianopsia. Magnetic resonance imaging evidenced a large suprasellar, retrochiasmatic mass with solid (calcified) and cystic components with interval progression compared with previous scans. Treatment options were discussed, and the patient consented to undergo maximum safe resection through an extended endoscopic endonasal approach. Surgical techniques are presented side by side with anatomic dissections to illustrate key steps of the procedure. The patient tolerated the procedure well, with gross total resection of the tumor and without complications or postoperative cerebrospinal fluid leaks. He was subsequently discharged home on postoperative day 5 with continued hormonal replacement therapy. On follow-up, the patient presented marked improvement in his cognitive function. The patient gave informed consent for the use of their images.

Sinonasal Outcomes Using Oral Corticosteroids in Patients with Chronic Rhinosinusitis with Nasal Polyps and Positive Sinonasal Cultures

Abstract Introduction Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and positive sinonasal bacterial cultures may be recalcitrant to topical therapy alone due to the additional local inflammatory burden associated with bacterial infection/colonization. Objectives To evaluate sinonasal outcomes in CRSwNP patients with a positive perioperative bacterial culture, who were treated with postoperative intranasal corticosteroids (INCS) alone versus INCS in combination with a short-term course of oral corticosteroids (OCS). Methods This is a retrospective chart review of CRSwNP patients. A total of 59 patients met inclusion criteria, including positive perioperative bacterial culture and treatment with INCS with or without concomitant use of OCS. Two cohorts were formed based on the chosen postoperative medical treatment; 32 patients underwent postoperative INCS alone, while 27 underwent INCS plus a ≤ 2-week course of OCS. The 22-item sinonasal outcome test (SNOT-22) scores and Lund-Kennedy scores (LKS) were assessed preoperatively, and at 2-week, 4-week, and 4 to 6 months after endoscopic sinus surgery (ESS). Results There were no statistically significant differences in postoperative sinonasal symptoms or endoscopic scores between the cohorts treated with INCS plus OCS versus those prescribed INCS alone (p > 0.05). Our regression model failed to demonstrate a relationship between the use of OCS and better sinonasal outcomes at 2-week, 4-week, and 4 to 6 months after ESS (p > 0.05). Conclusions Our study suggests that in a cohort of CRSwNP patients with recent bacterial infections, the postoperative use of combined OCS and INCS did not result in a statistical improvement of endoscopic and symptomatic outcomes over INCS irrigation alone. However, both treatment groups had a clinically significant improvement based on the Minimal Clinically Important Difference.

Sinonasal Outcomes Using Oral Corticosteroids in Patients with Chronic Rhinosinusitis with Nasal Polyps and Positive Sinonasal Cultures.

Introduction Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and positive sinonasal bacterial cultures may be recalcitrant to topical therapy alone due to the additional local inflammatory burden associated with bacterial infection/colonization. Objective To evaluate sinonasal outcomes in CRSwNP patients with a positive perioperative bacterial culture, who were treated with postoperative intranasal corticosteroids (INCS) alone versus INCS in combination with a short-term course of oral corticosteroids (OCS). Methods This is a retrospective chart review of CRSwNP patients. A total of 59 patients met inclusion criteria, including positive perioperative bacterial culture and treatment with INCS with or without concomitant use of OCS. Two cohorts were formed based on the chosen postoperative medical treatment; 32 patients underwent postoperative INCS alone, while 27 underwent INCS plus a ≤ 2-week course of OCS. The 22-item sinonasal outcome test (SNOT-22) scores and Lund-Kennedy scores (LKS) were assessed preoperatively, and at 2-week, 4-week, and 4 to 6 months after endoscopic sinus surgery (ESS). Results There were no statistically significant differences in postoperative sinonasal symptoms or endoscopic scores between the cohorts treated with INCS plus OCS versus those prescribed INCS alone ( p > 0.05). Our regression model failed to demonstrate a relationship between the use of OCS and better sinonasal outcomes at 2-week, 4-week, and 4 to 6 months after ESS ( p > 0.05). Conclusion Our study suggests that in a cohort of CRSwNP patients with recent bacterial infections, the postoperative use of combined OCS and INCS did not result in a statistical improvement of endoscopic and symptomatic outcomes over INCS irrigation alone. However, both treatment groups had a clinically significant improvement based on the Minimal Clinically Important Difference.

Relationship Between Alcohol Intolerance and Aspirin-Exacerbated Respiratory Disease (AERD): Systematic Review.

OBJECTIVE: Previous studies have suggested that patients with aspirin-exacerbated respiratory disease (AERD) have a high likelihood of alcohol intolerance. The purpose of this systematic review is to identify if there is sufficient evidence to confirm this correlation and the impact of medical therapy on subsequent alcohol tolerance. DATA SOURCES: PubMed, EMBASE, SCOPUS, EBSCO, Google Scholar, Cochrane Library, and Grey literature. We also performed snowballing on the identified observational studies (OS) for additional data. REVIEW METHODS: A systematic review was conducted from 1968 to 2022 to identify those studies describing AERD symptomatology triggered by alcohol intake. The primary outcome was to analyze the current literature for the association between alcohol intolerance and AERD symptoms. The secondary outcome looked for improvement in alcohol tolerance after aspirin desensitization or biological therapy. RESULTS: A total of 775 studies were identified and 40 abstracts were evaluated. From these, 5 studies met the inclusion criteria. Of the 5 manuscripts, there was 1 case-control, 2 cohort, and 2 cross-sectional studies. A total of 522 participants with AERD and a history of alcohol consumption were included, with 52.8% reporting at least 1 sinopulmonary exacerbation after alcohol intake. One of 3 studies noted improvement in alcohol tolerance after medical therapy with aspirin desensitization. CONCLUSION: The current literature suggests that patients with AERD have a high risk of alcohol intolerance. Additionally, aspirin desensitization may improve alcohol tolerance in this patient population.

Machine Learning Models to Forecast Outcomes of Pituitary Surgery: A Systematic Review in Quality of Reporting and Current Evidence.

BACKGROUND: The complex nature and heterogeneity involving pituitary surgery results have increased interest in machine learning (ML) applications for prediction of outcomes over the last decade. This study aims to systematically review the characteristics of ML models involving pituitary surgery outcome prediction and assess their reporting quality. METHODS: We searched the PubMed, Scopus, and Web of Knowledge databases for publications on the use of ML to predict pituitary surgery outcomes. We used the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) to assess report quality. Our search strategy was based on the terms "artificial intelligence", "machine learning", and "pituitary". RESULTS: 20 studies were included in this review. The principal models reported in each article were post-surgical endocrine outcomes (n = 10), tumor management (n = 3), and intra- and postoperative complications (n = 7). Overall, the included studies adhered to a median of 65% (IQR = 60-72%) of TRIPOD criteria, ranging from 43% to 83%. The median reported AUC was 0.84 (IQR = 0.80-0.91). The most popular algorithms were support vector machine (n = 5) and random forest (n = 5). Only two studies reported external validation and adherence to any reporting guideline. Calibration methods were not reported in 15 studies. No model achieved the phase of actual clinical applicability. CONCLUSION: Applications of ML in the prediction of pituitary outcomes are still nascent, as evidenced by the lack of any model validated for clinical practice. Although studies have demonstrated promising results, greater transparency in model development and reporting is needed to enable their use in clinical practice. Further adherence to reporting guidelines can help increase AI's real-world utility and improve clinical practice.

Endoscopic outcomes in patients with AERD treated with topical antibiotics and intranasal corticosteroids.

Background: Identifying effective therapy for recalcitrant chronic rhinosinusitis with nasal polyposis (CRSwNP) is a major challenge; and subtypes such as aspirin-exacerbated respiratory disease (AERD) are even more difficult to treat. Evidence on topical antibiotics use in (CRSwNP) is lacking. Current consensus guidelines recommend against its routine use, but recent reviews show some benefit when managing recalcitrant disease after endoscopic sinus surgery (ESS). Objective: Evaluate the effect of culture-directed topical antibiotics on sinonasal outcomes in AERD patients with a positive perioperative sinonasal bacterial culture who have undergone ESS. Methods: A retrospective cohort study of AERD patients with positive sinonasal culture, who underwent ESS from 2016 to 2021 was performed. Forty-four patients were identified and stratified based on their postoperative medical treatment. Twenty-six underwent postoperative intranasal corticosteroids (INCS) alone, while eighteen underwent INCS plus a 4-weeks treatment with topical antibiotics. SNOT-22 and Lund-Kennedy score (LKS) were assessed preoperatively and at 4-weeks and 4-6 months after ESS. Results: A statistically significant improvement in the 4-weeks and 4-6 months postoperative SNOT-22 and LKS were noted within both groups (p<0.05). However, only a statistically significant difference was found in the 4-weeks postoperative LKS when comparing between treatment groups (p=0.01). Our linear regression model demonstrated a relationship between the use of combined therapy with INCS and topical antibiotics and the LKS 4-weeks post ESS (p=0.015). Conclusion: In AERD patients with a confirmed sinus infection, the combination of culture-directed topical antibiotics and intranasal corticosteroid irrigations in the postoperative period can provide a short-term improvement in endoscopic scores.

Smell Outcomes in Olfactory Groove Meningioma Resection Through Unilateral versus Bilateral Transcranial Approaches: A Systematic Review and Meta-analysis.

OBJECTIVE: Olfactory disturbance is a common complication that occurs following the surgical resection of olfactory groove meningiomas (OGMs). There is little evidence on the best transcranial approach that minimizes rates of postoperative olfactory disturbance. The objective of this systematic review and meta-analysis is to compare smell outcomes after OGM resection in unilateral versus bilateral transcranial approaches. METHODS: A systematic review of the literature and meta-analysis was conducted using PUBMED, SCOPUS, and EMBASE in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The primary endpoint was incidence of new olfactory disturbance defined as anosmia or hyposmia, or both. Patients were classified as undergoing either a unilateral or bilateral approach. Data on presence of new postoperative olfactory deficits were used to generate standardized mean differences and 95% confidence intervals. RESULTS: Ten studies met the inclusion criteria for quantitative analysis, comprising 342 patients. A total of 216 patients underwent unilateral approaches while 126 underwent resection via bilateral approach. In the unilateral approach cohort, 17.1% experienced new postoperative olfactory disturbance following resection, compared with 19.2% of patients in the bilateral approach cohort. Forest plot did not reveal any significant difference in the incidence of new olfactory disturbance following either unilateral or bilateral approaches. CONCLUSIONS: Our data suggest that there is no significant difference between the investigated transcranial approaches and postoperative olfactory disturbances. Accordingly, our study suggests that further investigation with introduced experimental control could provide more insight into the capabilities and drawbacks of each route in relation to olfactory outcomes.

Effect of Partial Uncinectomy After Balloon Sinuplasty on Maxillary Sinus Irrigant Penetration: A Cadaveric Study.

OBJECTIVE: The uncinate process may play a role in the amount of irrigation penetrance. In this cadaver study, we aimed to investigate if the addition of partial uncinectomy provides better maxillary sinus irrigation penetrance than balloon sinuplasty (BSP) alone. STUDY DESIGN: Cadaveric study. SETTING: Simulation laboratory at the Mayo Clinic in Florida. METHODS: Five fresh-frozen human cadaveric heads (10 sides) were used to assess maxillary sinus irrigation penetration after 3 interventions performed sequentially: irrigation penetrance with no intervention, irrigation after BSP, and irrigation after BSP and partial removal of the uncinate. Penetrance was recorded with intrasinus endoscopy and scored by 4 blinded observers using a scale from 0 (no irrigation) to 5 (fully irrigated). The diameter of the maxillary ostium was measured before and after BSP. Internal consistency was evaluated with Cronbach's alpha. RESULTS: Mean ostium size increased from 4.1 to 6.8 mm after BSP (P = .013). Cronbach's alpha was 0.93. The median scores of irrigation penetration after no intervention, BSP, and BSP and partial uncinectomy were 2.5, 3, and 4, respectively. We found a significantly higher penetrance following partial uncinectomy plus BSP versus BSP alone (P = .008). Both interventions had a statistically significant difference in irrigation penetrance as compared with no intervention (P = .0001). CONCLUSION: Maxillary sinus irrigation penetration increased from baseline after BSP. The addition of a partial uncinectomy to the balloon dilation of the maxillary sinus was associated with a statistically significant increase in irrigation penetrance scores as compared with BSP alone.

Can Diffusion-Weighted Imaging Serve as an Imaging Biomarker for Acute Bacterial Rhinosinusitis?

Acute rhinosinusitis is defined as symptomatic inflammation of the mucosal lining of the nasal cavity and paranasal sinuses lasting less than four weeks. It is most commonly secondary to viral infection but is often challenging to distinguish from bacterial etiologies. Even with recommendations from several specialty societies, there continues to be a frequent practice of overprescribing oral antibiotics for acute rhinosinusitis, thus leading to multidrug-resistant organisms, and rendering oral medication useless when actually clinically warranted. We observed a potential non-invasive imaging biomarker that could predict which patients would benefit from anti-microbial therapy. Often computed tomography (CT) imaging is obtained by the provider before consultation with the otolaryngologist, sometimes leading to unnecessary radiation to the patient. In addition, there are no clear CT findings to make the diagnosis of acute rhinosinusitis. The diagnosis is challenging for all clinicians involved, and therefore, additional signs on other imaging modalities would be helpful. We present a series of four patients with incidentally discovered culture-positive acute rhinosinusitis. Patients with incidentally discovered culture-positive acute rhinosinusitis were found to also have magnetic resonance imaging (MRI) that showed corresponding restricted diffusion on diffusion-weighted imaging (DWI). An imaging biomarker for acute bacterial rhinosinusitis may improve the appropriate use of antibiotic therapy. DWI MRI should be further investigated as a potential candidate screening modality.

Endoscopic endonasal transclival approach to the ventral brainstem: Radiologic, anatomic feasibility and nuances, surgical limitations and future directions.

The endoscopic endonasal transclival approach (EETA) is less invasive than traditional open approaches; however, there is currently limited data on the pre-operative features that may predict success of the EETA. Surgical landmarks and exposure of the EETA and expanded EETA are assessed. We retrospectively measured multiple anatomic features in 154 adult dry skulls, 22 C1 and C2 dry bone vertebrae, and 500 paranasal sinus computed tomography (CT) scans. We also dissected 13 formalin-fixed, silicone-injected adult cadaveric heads. Relevant qualitative and quantitative data were obtained with CT (n = 10) and cadaveric dissection (n = 13). They are expressed as mean (SD), as appropriate and compared with unpaired t tests. Categorical variables were compared with χ2 tests. We determined the prevalence of clival and sphenoid sinus anatomic variations and assessed potential exposure of the craniovertebral region, based on the relative position of the nasal bone tip, posterior point of the hard palate, and their relation to the position of C1 and C2. Depending on anatomic features, EETA should allow visualization of the ventral brainstem. The mean (SD) dimensions of the surgical window for EETA were 43.2 (5.1) × 18.3 (1.1) mm, in the craniocaudad and horizontal dimensions, respectively. The craniocaudad dimension enlarged to 60.2 (4.7) mm with expanded EETA. The EETA allowed satisfactory exposure for odontoid and C1 anterior arch resection (expanded EETA) in all specimens, regardless of the orientation of the palate. The combination of preoperative radiographic assessment and intraoperative considerations allows safe and effective application and facilitate selection of the most appropriate approach.

Radiographic and Hormonal Regression in Prolactinomas: An Analysis of Treatment Failure.

OBJECTIVE: First-line treatment for prolactin-producing pituitary adenomas is dopamine agonist (DA) therapy. This is the first study to analyze the rate of radiographic and hormonal regression of prolactinomas in response to DA therapy to better understand what time frame we consider DA treatment failure. METHODS: We searched the electronic medical records of 3 tertiary care medical institutions for patients with prolactinomas. The primary outcome was tumor volume and prolactin (PRL) levels at various time points. The secondary outcome was indicators of treatment failure. Modeling by both linear and exponential models was tested to determine potential predictors of response magnitude and treatment failure by multivariate and regression analyses respectively. RESULTS: There were 99 patients (53% male) included in this analysis. The mean patient age was 42.7 years ± 14.5, and mean width/volume of tumor at diagnosis was 12.3 mm and 1.3 cm3, respectively. The mean PRL level at diagnosis was 593.2 ng/mL (79-7913). Modeling indicated a plateau at 68.2% initial volume (95% confidence interval 61.7-73.5) by 12.6 months and a PRL plateau of 21.4 ng/mL (95% confidence interval 0-92.5) by 3.3 months. Multivariate analyses revealed male sex (odds ratio 0.168; P = 0.036) to be a predictor of faster PRL response to DA therapy. CONCLUSIONS: Prolactinomas plateau in PRL levels and the rate of size regression within the first year of DA treatment. Prolactinomas with lack of size regression and failure to reach normalization of PRL levels by 12 months may be considered for other management strategies.

Endocrine and Visual Outcomes Following Gross Total Resection and Subtotal Resection of Adult Craniopharyngioma: Systematic Review and Meta-Analysis.

OBJECTIVE: The optimal surgical strategy for management of adult patients with craniopharyngioma remains controversial. To analyze the functional outcomes ofadult patients with gross total resection (GTR) and subtotal resection (STR) of craniopharyngioma. METHODS: MEDLINE, EMBASE, Scopus, and Cochrane databases were searched from inception to July 19, 2018, for articles comparing postoperative endocrine function, vision, complications, and recurrence rates for adult patients with GTR and STR of craniopharyngioma. The articles were analyzed by meta-analysis of proportions using a random-effects model to calculate summary odds ratios (ORs). RESULTS: The initial search resulted in 2468 studies and 540 studies selected for full text review. Seventeen studies were included in the final analyses with 748 patients in the GTR cohort and 559 patients in the STR cohort. GTR resulted in a significantly lower likelihood of recurrence when compared with STR (OR, 0.106; 95% confidence interval [CI], 0.067-0.168; P < 0.001), but a significantly greater likelihood of panhypopituitarism (OR, 2.063; 95% CI, 1.058-4.024; P = 0.034) and permanent diabetes insipidus (OR, 2.776; 95% CI, 1.321-5.832; P = 0.007). There was no significant difference between the groups for postoperative worsened vision (P = 0.868), improved vision (P = 0.876), pathologic weight gain (P = 0.724), cerebrospinal fluid leak (P = 0.788), complications (P = 0.656), or death (P = 0.261). CONCLUSIONS: This is the first systematic review of functional outcomes of adult patients with craniopharyngioma. GTR results in decreased likelihood of recurrence, but increased likelihood of postoperative panhypopituitarsm and permanent diabetes insipidus. Surgeons should be aware of these associations when determining the optimal operative strategy for adult patients with craniopharyngioma.

Ectopic Prolactinoma Presenting as Bacterial Meningitis: A Diagnostic Conundrum.

BACKGROUND: Prolactinomas may rarely present with meningitis and cerebrospinal fluid (CSF) rhinorrhea secondary to erosion of the wall of the sella turcica. It is even more uncommon for this abnormal communication to be caused by an ectopic prolactinoma arising from the sphenoid sinus and eroding into the sella. This atypical growth pattern makes diagnosis very difficult because there may be no displacement of the normal pituitary gland. The first reported case of a patient with an ectopic prolactinoma originating within the sphenoid sinus presenting primarily with meningitis is presented, and the management strategy and surgical and nonsurgical treatment options are discussed. CASE DESCRIPTION: A 48-year-old woman presented with confusion, low-pressure headache, and fever. A lumbar puncture revealed Streptococcus pneumoniae meningitis, and she was placed on intravenous penicillin G. After initiation of antibiotics, she noticed salty tasting postnasal fluid leakage. Imaging was remarkable for bony erosion of the sphenoid sinus wall by a soft tissue mass growing from within the sinus, with no disruption of the normal pituitary gland. A biopsy was then performed with an endoscopic transnasal transsphenoidal approach, and the CSF leak was repaired with a pedicled nasoseptal flap. The final pathology was prolactinoma, and she was placed on cabergoline. CONCLUSIONS: Ectopic prolactinomas may rarely present as meningitis secondary to retrograde transmission of bacteria through a bony defect in the sphenoid sinus, and must be included in the differential diagnosis of any sphenoid sinus mass. Management should first address the infection, followed by surgical repair of the bony defect.

Vestibular perception and the vestibulo-ocular reflex in young and older adults.

OBJECTIVES: Quantification of the perceptual thresholds to vestibular stimuli may offer valuable complementary information to that provided by measures of the vestibulo-ocular reflex (VOR). Perceptual thresholds could be particularly important in evaluating some subjects, such as the elderly, who might have a greater potential of central as well as peripheral vestibular dysfunction. The authors hypothesized that perceptual detection and discrimination thresholds would worsen with aging, and that there would be a poor relation between thresholds and traditional measures of the angular VOR represented by gain and phase on rotational chair testing. DESIGN: The authors compared the detection and discrimination thresholds of 19 younger and 16 older adults in response to earth-vertical, 0.5 Hz rotations. Perceptual results of the older subjects were then compared with the gain and phase of their VOR in response to earth-vertical rotations over the frequency range from 0.025 to 0.5 Hz. RESULTS: Detection thresholds were found to be 0.69 ± 0.29 degree/sec (mean ± standard deviation) for the younger participants and 0.81 ± 0.42 degree/sec for older participants. Discrimination thresholds in younger and older adults were 4.83 ± 1.80 degree/sec and 4.33 ± 1.57 degree/sec, respectively. There was no difference in either measure between age groups. Perceptual thresholds were independent of the gain and phase of the VOR. CONCLUSIONS: These results indicate that there is no inevitable loss of vestibular perception with aging. Elevated thresholds among the elderly are therefore suggestive of pathology rather than normal consequences of aging. Furthermore, perceptual thresholds offer additional insight, beyond that supplied by the VOR alone, into vestibular function.

Human discrimination of rotational velocities.

Vestibular reflexes are critically important for stabilizing gaze and maintaining posture, but comparatively little is known about conscious perceptions of vestibular stimuli and how they may relate to balance function. We used psychophysical methods to determine the ability of normal subjects and a vestibular-deficient subject to discriminate among velocities of earth-vertical sinusoidal rotations. Discrimination thresholds in normal subjects rose from 2.26 deg/s at a peak velocity of 20 deg/s up to 5.16 deg/s at 150 deg/s. The relationship between threshold and peak angular velocity was well described by the power law function DeltaI = 0.88I(0.37), where I is the magnitude of the stimulus and DeltaI is the discrimination threshold. The subject with bilateral vestibular hypofunction had thresholds more than an order of magnitude worse than normals. The performance of normal subjects is much better than that predicted by Weber's Law, which states that discrimination thresholds increase proportionally with stimulus magnitude (i.e., DeltaI/I = C, where C is the "Weber fraction"). This represents a remarkable exception to other sensory systems and may reflect the vestibular system's ability to stabilize gaze and maintain posture even at high stimulus intensities. Quantifying this relationship may help elucidate the role of higher-level processes in maintaining balance and provide information to diagnose and guide therapy of patients with central causes for imbalance.

Gentian violet and ferric ammonium citrate disrupt Pseudomonas aeruginosa biofilms.

OBJECTIVE/HYPOTHESIS: Bacterial biofilms are resistant to antibiotics and may contribute to persistent infections including chronic otitis media and cholesteatoma. Discovery of substances to disrupt biofilms is necessary to treat these chronic infections. Gentian violet (GV) and ferric ammonium citrate (FAC) were tested against Pseudomonas aeruginosa biofilms to determine if either substance can reduce biofilm volume. STUDY DESIGN: The biofilm volume and planktonic growth of PAO1 and otopathogenic P. aeruginosa (OPPA8) isolated from an infected cholesteatoma was measured in the presence of GV or FAC. METHODS: OPPA8 and PAO1 expressing a green fluorescent protein plasmid (pMRP9-1) was inoculated into a glass flow chamber. Biofilms were grown under low flow conditions for 48 hours and subsequently exposed to either GV or FAC for an additional 24 hours. Biofilm formation was visualized by confocal laser microscopy and biofilm volume was assayed by measuring fluorescence. Planktonic cultures were grown under standard conditions with GV or FAC. Statistical analysis was performed by Student t test and one-way ANOVA. RESULTS: GV reduced PAO1 and OPPA8 biofilm volume (P < .01). GV delayed the onset and rate of logarithmic growth in both strains. FAC reduced OPPA8 biofilm volume (P < .01), but did not effect of PAO1 biofilms. FAC had no effect on planktonic growth. CONCLUSIONS: The efficacy of GV in disrupting biofilms in vitro suggests that it may disrupt biofilms in vivo. The effect of FAC on Pseudomonas aeruginosa biofilms is strain dependent. Strain differences in response to increasing iron concentration and biofilm morphology stress the importance of studying clinically isolated strains in testing antibiofilm agents.

The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis.

Metastatic cancers, once established, are the primary cause of mortality associated with cancer. Previously, we used a genomic approach to identify metastasis-associated genes in cancer. From this genomic data, we selected ezrin for further study based on its role in physically and functionally connecting the actin cytoskeleton to the cell membrane. In a mouse model of osteosarcoma, a highly metastatic pediatric cancer, we found ezrin to be necessary for metastasis. By imaging metastatic cells in the lungs of mice, we showed that ezrin expression provided an early survival advantage for cancer cells that reached the lung. AKT and MAPK phosphorylation and activity were reduced when ezrin protein was suppressed. Ezrin-mediated early metastatic survival was partially dependent on activation of MAPK, but not AKT. To define the relevance of ezrin in the biology of metastasis, beyond the founding mouse model, we examined ezrin expression in dogs that naturally developed osteosarcoma. High ezrin expression in dog tumors was associated with early development of metastases. Consistent with this data, we found a significant association between high ezrin expression and poor outcome in pediatric osteosarcoma patients.