Thomas Muelleman

Perineural growth in head and neck squamous cell carcinoma: A review

Perineural growth is a unique route of tumor metastasis that is associated with poor prognosis in several solid malignancies. It is diagnosed by the presence of tumor cells inside the neural space seen on histological or imaging evaluations. Little is known about molecular mechanisms involved in the growth and spread of tumor cells in neural spaces. The poor prognosis associated with perineural growth and lack of targeted approaches necessitates the study of molecular factors involved in communication between tumor and neural cells. Perineural growth rates, shown to be as high as 63% in head and neck squamous cell carcinoma (HNSCC), correlate with increased local recurrence and decreased disease-free survival. Here we describe the literature on perineural growth in HNSCC. In addition, we discuss factors implicated in perineural growth of cancer. These factors include brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 and -4, glial cell-line derived neurotrophic factor (GDNF), the neural cell adhesion molecule (NCAM), substance P (SP), and chemokines. We also explore the literature on membrane receptors, including the Trk family and the low-affinity nerve growth factor receptor. This review highlights areas for further study of the mechanisms of perineural invasion which may facilitate the identification of therapeutic targets in HNSCC.

Individualized Surgical Approach Planning for Petroclival Tumors Using a 3D Printer.

Objectives To determine the utility of three-dimensional (3D) printed models in individualized petroclival tumor resection planning by measuring the fidelity of printed anatomical structures and comparing tumor exposure afforded by different approaches. Design Case series and review of the literature. Setting Tertiary care center. Participants Three patients with petroclival lesions. Main Outcome Measures Subjective opinion of access by neuro-otologists and neurosurgeons as well as surface area of tumor exposure. Results Surgeons found the 3D models of each patients skull and tumor useful for preoperative planning. Limitations of individual surgical approaches not identified through preoperative imaging were apparent after 3D models were evaluated. Significant variability in exposure was noted between models for similar or identical approaches. A notable drawback is that our printing process did not replicate mastoid air cells. Conclusions We found that 3D modeling is useful for individualized preoperative planning for approaching petroclival tumors. Our printing techniques did produce authentic replicas of the tumors in relation to bony structures.

Epidemiology of Dizzy Patient Population in a Neurotology Clinic and Predictors of Peripheral Etiology

OBJECTIVE To compare the proportion of peripheral versus nonperipheral dizziness etiologies among all patients, inclusive of those presenting primarily or as referrals, to rank diagnoses in order of frequency, to determine whether or not age and sex predict diagnosis, and to determine which subgroups tended to undergo formal vestibular testing. STUDY DESIGN Retrospective cohort. SETTING Academic neurotology clinic. PATIENTS Age greater than 18 neurotology clinic patients with the chief complaint of dizziness. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Age, sex, diagnosis, record of vestibular testing. RESULTS Two thousand seventy-nine patients were assigned 2,468 diagnoses, of which 57.7 and 42.3% were of peripheral and nonperipheral etiologies, respectively. The most common diagnoses were Ménières (23.0%), vestibular migraine (19.3%), benign paroxysmal positional vertigo (BPPV) (19.1%), and central origin, nonmigraine (16.4%). Peripheral diagnoses are more likely to be found in men than in women (odds ratio [OR] 1.59). Peripheral diagnoses were most likely to be found in the 60 to 69 age group (OR 3.82). There was not a significant difference in rate of vestibular testing between women and men. Among patients with two diagnoses, the most common combinations were vestibular migraine and BPPV then vestibular migraine and Ménières. CONCLUSIONS A large proportion of patients seen for the chief complaint of dizziness in the neurotology clinic were found not to have a peripheral etiology of their symptoms. These data challenge a prevalent dogma that the most common causes of dizziness are peripheral: BPPV, vestibular neuritis, and Ménières disease. Age and sex are statistically significant predictors of peripheral etiology of dizziness.

Endoscopically Assisted Drilling, Exposure of the Fundus through a Presigmoid Retrolabyrinthine Approach: A Cadaveric Feasibility Study:

The presigmoid retrolabyrinthine approach to the cerebellopontine angle is traditionally described to not provide access to the internal auditory canal (IAC). We aimed to evaluate the extent of the IAC that could be exposed with endoscopically assisted drilling and to measure the percentage of the IAC that could be visualized with the microscope and various endoscopes after drilling had been completed. Presigmoid retrolabyrinthine approaches were performed bilaterally on 4 fresh cadaveric heads. We performed endoscopically assisted drilling to expose the fundus of the IAC, which resulted in exposure of the entire IAC in 8 of 8 temporal bone specimens. The microscope afforded a mean view of 83% (n = 8) of the IAC. The 0°, 30°, 45°, and 70° endoscope each afforded a view of 100% of the IAC in 8 of 8 temporal bone specimens. In conclusion, endoscopic drilling of the IAC of can provide an extradural means of exposing the entire length of the IAC while preserving the labyrinth.

Effect of Piecemeal vs En Bloc Approaches to the Lateral Temporal Bone on Survival Outcomes

Objectives Lateral temporal bone resection (LTBR) has traditionally been performed en bloc in accordance with oncologic principles. Occasionally, this is not possible due to a low tegmen or lateralized vasculature. We sought to determine if outcomes of piecemeal and en bloc LTBR are comparable. Study Design Retrospective review. Setting Two academic medical centers. Subjects and Methods Multi-institutional retrospective cohort study. Current Procedural Terminology codes were used to identify patients with T1 to T3 squamous cell carcinoma of the external auditory canal (EAC) who underwent LTBR from 2005 to 2015. Kaplan-Meier curves were constructed to compare total survival between the 2 treatment approaches. Pairwise comparisons were performed using χ2 and Fisher exact tests (significance at P = .05), as appropriate. Results Twenty-five patients were identified. Ten patients underwent en bloc LTBR; 15 underwent piecemeal LTBR. Median follow-up time was 11 months (range, 1-60 months). There was not a significant difference in overall survival between en bloc (38.9 months; 95% confidence interval [CI], 22.7-55.2) compared to piecemeal (37.5 months; 95% CI, 21.1-53.9) procedures (P = .519). Estimates of disease-free survival also did not reveal statistically significant differences: estimated mean disease-free survival was 48.1 months (95% CI, 33.7-62.6) in en bloc patients and 32.5 months (95% CI, 17.1-47.8) in piecemeal patients (P = .246). Conclusion These data suggest that piecemeal resection can be considered for cases of squamous cell carcinoma involving the external auditory canal where anatomic constraints preclude a safe en bloc resection. Larger studies or studies with a longer follow-up time may provide improved insight into survival comparisons.

In Reply to: “Effect of Piecemeal vs En Bloc Approaches to the Lateral Temporal Bone on Survival Outcomes”

We read with great interest the article by Muelleman et al concerning piecemeal resection versus lateral temporal bone resection (LTBR) of T1-T3 squamous cell carcinoma (SCC). The authors state that piecemeal resection might be required in cases of low-lying tegmen or laterally placed vascular structures. In the >250 LTBRs performed by our group, these 2 anatomic constraints are exceedingly rare (<5%). Anatomic constraints to standard en bloc LTBR are addressed with careful surgical technique. Low-lying tegmen is handled by following the middle fossa dura medially and anteriorly until the temporomandibular joint capsule is reached. In cases where this bone is <2 mm thick, the superior bony canal is drilled away, but the remaining canal is still intact, allowing en bloc resection. The high-riding jugular bulb and the laterally placed carotid artery present their own challenges. The high-riding jugular bulb is always medial to the facial nerve, and the facial nerve is generally preserved with en bloc LTBR. Thus, staying lateral to the facial nerve and working medial to the annulus allows the surgeon to surpass the highriding jugular. The laterally placed carotid is slightly more difficult to handle and is why osteotomes are not used. Intraoperatively, the lateral carotid canal is identified in the middle ear after the hypotympanic air cells have been removed. The surgeon can then follow the carotid canal and drill between it and the annulus to complete the inferior canal cut. The authors do not adequately describe their patient population. It is unclear if all cases were primary SCC of the ear canal or if they included external ear SCC, periauricular SCC, or metastatic SCC to the parotid gland that secondarily involved the ear canal. The authors omit other confounders between the groups, such as age, bone invasion, perineural invasion, and lymph node metastases. The reason for piecemeal resection is not included. From an oncologic viewpoint, the follow-up time in this series is inadequate (median, 11 months; 40% with <4 months), given that the mean time to recurrence for SCC of the ear canal is 13 months but can be as long as 3 years. In fact, one is unable to determine if there is a simple difference in follow-up time between the groups. This article has too many deficiencies to make any conclusions regarding oncologic safety of such an approach.

Impact of Resident Participation on Operative Time and Outcomes in Otologic Surgery

Objectives To describe the impact of resident involvement in tympanoplasty on operative time and surgical complication rates. Study Design Case series with chart review. Setting Tertiary medical center. Subjects and Methods Current Procedural Terminology codes were used to identify patients in the 2011-2014 public use files of the American College of Surgeons National Surgical Quality Improvement Program who underwent a tympanoplasty or tympanomastoidectomy. Cases were included if the database indicated whether the operating room was staffed with an attending alone or an attending with residents. Categorical and continuous variables were compared with chi-square, Fisher’s exact, and Mann-Whitney U tests. Generalized linear models with a log-link and gamma distribution were used to examine the factors affecting operative time. Results Overall, 1045 cases met our study criteria (tympanoplasty, n = 797; tympanomastoidectomy, n = 248). Resident involvement increased mean operative time for tympanoplasties by 46% (107 vs 73 minutes, P < .001) and tympanomastoidectomies by 49% (175 vs 117 minutes, P < .001). While controlling for confounding factors, the variable with the largest impact on operative time was resident involvement. There were no significant differences observed in the rate of surgical complications between attending-alone and attending-resident cases. Conclusion Resident involvement in tympanoplasty and tympanomastoidectomy did not affect the surgical complication rate. Resident involvement increased operative time for tympanoplasties and tympanomastoidectomies; however, the specific reasons for the increase are not explained by the available data.

Hypertrophic Pachymeningitis of the Internal Auditory Canal: A Rare Case of Unilateral Sudden Sensorineural Hearing Loss

Objectives: To describe and increase awareness of a rare cause of unilateral sudden sensorineural hearing loss. Methods: Case report and literature review. Results: We present a 66-year-old female who suffered left-sided sudden sensorineural hearing loss and dizziness. Diagnostic magnetic resonance imaging (MRI) did not reveal masses or lesions along the eighth cranial nerve or in the inner ear. Upon eventual referral to neurotology clinic, hypertrophic pachymeningitis of her left internal auditory canal and adjacent middle and posterior fossa dura were identified. The ensuing laboratory workup for autoimmune and infectious etiology revealed mild elevation of ACE 93 (9-67) but otherwise normal results. Conclusions: Idiopathic hypertrophic pachymeningitis is a diagnosis of exclusion. Neoplastic, infectious, and autoimmune causes must be ruled out. The prevailing treatment for this condition is high-dose corticosteroids. This entity should be considered when evaluating MRI scans obtained in the setting of sudden sensorineural hearing loss.

Petrous Apex Pneumatization: Influence on Postoperative Cerebellopontine Angle Tumor Cerebrospinal Fluid Fistula

Objective: Multiple investigators have sought to identify risk factors for cerebrospinal fluid (CSF) leak following cerebellopontine angle (CPA) tumor resection. We evaluated whether pneumatization of the petrous apex (PA) is a risk factor for CSF fistula. Method: We conducted a retrospective chart review at 2 major tertiary academic institutions undergoing CPA tumor resection and analyzed their respective head or temporal computed tomography (CT) scans if available. Results: A total of 91 cases were identified; 51 (64%) demonstrated PA pneumatization, and a total of 17 CSF leaks were identified. We discovered higher rates of CSF leak (25.0% vs 13.7%; P = .273) and CSF rhinorrhea (15.0% vs 5.9%; P = .174) in patients with PA pneumatization compared to those without PA pneumatization. Conclusions: Isolated PA pneumatization may be a risk factor and communication pathway for CSF fistula. Further studies will need to be broadened across multiple institutions to draw any additional and stronger conclusions.

Therapeutic Mastoidectomy Does Not Increase Postoperative Complications in the Management of the Chronic Ear

OBJECTIVE Tympanoplasty with or without concurrent therapeutic mastoidectomy is a controversial topic in the management of chronic ear disease. We sought to describe whether there is a significant difference in postoperative complications. STUDY DESIGN Retrospective cohort study. SETTING American College of Surgeons National Surgical Quality Improvement Program public files. PATIENTS Current procedural terminology codes were used to identify patients with chronic ear disease undergoing tympanoplasty ± concurrent mastoidectomy in the 2011 to 14 American College of Surgeons National Surgical Quality Improvement Program files. INTERVENTION Therapeutic. MAIN OUTCOME MEASURES Variables were compared with χ, Fischers exact, and Mann-Whitney U tests, as appropriate to analyze postoperative complications between tympanoplasty with or without concurrent mastoidectomy. To account for confounding factors, presence of a complication was analyzed in binary logistic regression. Analysis considered sex, hypertension, obesity, advanced age, diabetes, smoking status, American Society of Anesthesiologists Physical status, procedure. RESULTS There were 4,087 patients identified meeting criteria (tympanoplasty = 2,798, tympanomastoidectomy = 1,289). There was no statistical difference in postoperative complications (tympanoplasty n = 49 [1. 8%], tympanomastoidectomy n = 33 [2. 6%]; p = 0. 087) or return to the operating room (tympanoplasty = 4 [0. 1%], tympanomastoidectomy = 6 [0. 5%]; p = 0. 082). Binary logistic regression demonstrated smoking as a predictor of a postoperative complication (OR: 1. 758, 95% CI: 1. 084-2. 851; p = 0. 022), while concurrent mastoidectomy did not significantly increase the risk of complication (OR: 1. 440, 95% CI: 0. 915-2. 268; p = 0. 115). There was a significant difference in mean operative time between tympanoplasty and tympanomastoidectomy: 85.7 versus 154.23 min, p < 0. 001. CONCLUSION In the management of chronic ear disease, tympanoplasty with concurrent mastoidectomy increases time under anesthesia, but it is not associated with any increased postoperative complications compared with tympanoplasty alone.