Neoadjuvant presurgical PD-1 inhibition in oral cavity squamous cell carcinoma.

Oral cavity squamous cell carcinoma (OCSCC) is a prevalent surgically treated subset of head and neck cancer with frequent recurrence and poor survival. Immunotherapy has demonstrated efficacy in recurrent/metastatic head and neck cancer. However, whether antitumor responses could be fostered by neoadjuvant presurgical immunotherapy remains unclear. Using a Simon's two-stage design, we present results of a single-arm phase-II trial where 12 patients with stage II-IVA OCSCC received 3 to 4 biweekly doses of 3 mg/kg nivolumab followed by definitive surgical resection with curative intent. Presurgical nivolumab therapy in this cohort shows an overall response rate of 33% (n = 4 patients; 95% CI: 12%-53%). With a median follow up of 2.23 years, 10 out of 12 treated patients remain alive. Neoadjuvant nivolumab is safe, well-tolerated, and is not associated with delays in definitive surgical treatment in this study. This work demonstrates feasibility and safety for incorporation of nivolumab in the neoadjuvant setting for OCSCC (ClinicalTrials.gov: NCT03021993).

Free Flap Inset Techniques in Salvage Laryngopharyngectomy Repair: Impact on Fistula Formation and Function.

OBJECTIVE: To characterize pharyngocutaneous fistula (PCF) rates and functional outcomes following microvascular free tissue transfer (MVFTT) reconstruction of salvage total laryngectomy (STL) with a review of two different flap inset techniques and a review of the literature. METHODS: Retrospective review. RESULTS: Review of the literature revealed 887 patients who underwent STL MVFTT from 14 references. Ninety-six STL MVFTTs were performed by the authors, with 36 (38%) patients undergoing multilayer fascial underlay (MLFU) closure and 60 (62%) a standard single layer closure (SLC). One (3%) PCF occurred in the MLFU group compared to 12 (20%) in the SLC cohort (P = .03). Postoperative gastrostomy (G)-tube dependence was lower following MLFU closure compared to SLC (25% vs. 57%, P < .01), whereas pharyngoesophageal stricture (PES) (28% vs. 38%), tracheoesophageal puncture (TEP) placement (42% vs. 42%), and TEP usage (87% vs. 88%) did not significantly differ (P > .05). Compared to pooled rates from the literature, patients who underwent a MLFU MVFTT inset technique demonstrated significantly lower PCF incidence (3% vs. 23%, P < .01) without significant differences in PES (28% vs 23%, P = .55), G-tube dependence (25% vs. 23%, P = .25), or TEP placement (42% vs. 59%, P = .09). CONCLUSION: Despite MVFTT reconstruction after STL, G-tube dependence, PCF formation, and limitations of speaking rehabilitation (TEP) remain a significant issue. Modification of MVFTT inset may provide an opportunity to reduce PCF incidence without affecting other functional outcomes. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E875-E881, 2021.

Intraoperative vasopressors in head and neck free flap reconstruction.

INTRODUCTION: Historically, there were concerns vasopressors impair free flap outcomes, but recent studies suggest vasopressors are safe. Here we investigate this controversy by (1) evaluating vasopressors' effect on head and neck free-flap survival and surgical complications, and (2) performing soft tissue and bony subset analysis. PATIENTS AND METHODS: Post hoc analysis was performed of a single-blinded, prospective, randomized clinical trial at a tertiary care academic medical center involving patients ≥18 years old undergoing head and neck free flap reconstruction over a 16-month period. Patients were excluded if factors prevented accurate FloTrac™ use. Patients were randomized to traditional volume-based support, or goal-directed support including vasopressor use. Primary data was obtained by study personnel through intraoperative data recording and postoperative medical record review. RESULTS: Forty-one and 38 patients were randomized to traditional and pressor-based algorithms, respectively. Flap survival was 95% (75/79). There was no significant difference between the pressor-based and traditional protocols' flap failure (1/38 [3%] vs. 3/41 [7%], RR 0.36, 95% CI of RR 0.04-3.31, p = .63) or flap-related complications (12/38 [32%] vs. 18/41 [44%], RR 0.72, 95% CI 0.40-1.29, p = .36) Soft tissue flaps had surgical complication rates of 12/30 (40%) and 9/27 (33%) for traditional and pressor-based protocols, respectively. Bony flaps had surgical complication rates of 6/11 (55%), and 3/11 (27%) for traditional and pressor-based protocols, respectively. CONCLUSIONS: Intraoperative goal-directed vasopressor administration during head and neck free flap reconstruction does not appear to increase the rate of flap complications or failures.

Evaluation of a novel telemedicine-based intervention to manage body image disturbance in head and neck cancer survivors.

OBJECTIVES: The study aimed to evaluate the feasibility, acceptability, and preliminary clinical impact of BRIGHT (Building a Renewed ImaGe after Head & neck cancer Treatment), a novel telemedicine-based cognitive-behavioral intervention to manage body image disturbance (BID) in head and neck cancer (HNC) survivors. METHODS: Head and neck cancer survivors with BID were enrolled into a single-arm pilot trial. Participants completed study measures at baseline, 1- and 3-months post-BRIGHT to assess its acceptability and clinical impact. Participants completed semi-structured interviews to evaluate the feasibility and acceptability of BRIGHT and refine the intervention. RESULTS: Ten HNC survivors with BID were enrolled into the trial of tablet-based BRIGHT. BRIGHT was feasible, as judged by low dropout (n = 1), high session completion rates (100%; 45/45) and low rates of technical issues with the tablet-based delivery (11% minor; 0% major). Ninety percent of participants were highly likely to recommend BRIGHT, reflecting its acceptability. BRIGHT was associated with a 34.5% reduction in mean Body Image Scale scores at 1-month post-BRIGHT (mean difference from baseline = 4.56; 95% CI 1.55, 7.56), an effect that was durable at 3-months post-BRIGHT (mean decrease from baseline = 3.56; 95% CI 1.15-5.96). Program evaluation revealed high levels of satisfaction with BRIGHT, particularly the delivery platform. During the qualitative evaluation, participants highlighted that BRIGHT improved image-related coping behavior. CONCLUSIONS: BRIGHT is feasible, acceptable to HNC survivors, and has significant potential as a novel approach to manage BID in HNC survivors. Additional research is necessary to refine BRIGHT and evaluate its clinical efficacy and scalability.

Temporal Trajectory of Body Image Disturbance in Patients with Surgically Treated Head and Neck Cancer.

OBJECTIVES: To characterize the temporal trajectory of body image disturbance (BID) in patients with surgically treated head and neck cancer (HNC). STUDY DESIGN: Prospective cohort study. SETTING: Academic medical center. SUBJECTS AND METHODS: Patients with HNC who were undergoing surgery completed the Body Image Scale (BIS), a validated patient-reported outcome measure of BID, pretreatment and 1, 3, 6, 9, and 12 months posttreatment. Changes in BIS scores (ΔBIS) relative to pretreatment (primary endpoint) were analyzed with a linear mixed model. Associations between demographics, clinical characteristics, psychosocial attributes, and persistently elevated BIS scores and increases in BIS scores ≥5 points relative to pretreatment (secondary endpoints) were analyzed through logistic regression. RESULTS: Of the 68 patients, most were male (n = 43), had oral cavity cancer (n = 37), and underwent microvascular reconstruction (n = 45). Relative to baseline, mean ΔBIS scores were elevated at 1 month postoperatively (2.9; 95% CI, 1.3-4.4) and 3 (3.2; 95% CI, 1.5-4.9) and 6 (1.8; 95% CI, 0.02-3.6) months posttreatment before returning to baseline at 9 months posttreatment (0.9; 95% CI, -0.8 to 2.5). Forty-three percent of patients (19 of 44) had persistently elevated BIS scores at 9 months posttreatment relative to baseline, and 51% (31 of 61) experienced an increase in BIS scores ≥5 relative to baseline. CONCLUSIONS: In this cohort of patients surgically treated for HNC, BID worsens posttreatment before returning to pretreatment (baseline) levels at 9 months posttreatment. However, 4 in 10 patients will experience a protracted course with persistent posttreatment body image concerns, and half will experience a significant increase in BIS scores relative to pretreatment levels.

Prognostic factors associated with achieving total oral diet following osteocutaneous microvascular free tissue transfer reconstruction of the oral cavity.

INTRODUCTION: Osteocutaneous microvascular free tissue transfer (OMFTT) is the current standard in reconstruction of large bony defects of the oral cavity. Although being able to swallow ranks as a top priority for patients undergoing OMFTT, factors associated with achieving an oral diet following surgery remain unclear. We sought to describe the rate of total oral diet achievement, and to identify possible pre-, intra-, and post-operative factors associated with achievement in patients undergoing OMFTT. METHODS: Retrospective review between January 1, 2010 and March 31, 2018 at two tertiary academic centers. RESULTS: 249 patients (67% male, mean age 58 years) met inclusion criteria, with a median follow up of 15 months. Overall, 142 (57%) of patients achieved a total PO diet post-operatively, with median time to achievement of 3.2 months. Multivariate analysis identified that lack of concurrent glossectomy (SHR 1.72 [1.09-2.70], p = 0.02), N0/1 disease (SHR 1.92 [1.16-3.13], p = 0.011), avoidance of post-operative fistula formation (SHR 1.96 [1.22-3.23], p = 0.005), pre-operative G-tube independence (SHR 3.33 [1.69-6.25], p < 0.001), and successful dental rehabilitation (SHR 2.08 [1.43-3.03], p < 0.001) are independently associated with total oral diet achievement. CONCLUSIONS: Bony resections not requiring glossectomy, limited nodal disease burden, pre-operative gastrostomy-independence, avoidance of post-operative fistula, and dental rehabilitation are independently associated with achievement of total oral diet following OMFTT reconstruction of the oral cavity. Counseling patients on associated risk factors is important in guiding post-treatment expectations. Minimization of post-operative fistula, and maximization of dental rehabilitation may significantly improve total oral diet achievement in this patient population.

Prognostic factors associated with achieving total oral diet after glossectomy with microvascular free tissue transfer reconstruction.

OBJECTIVE: Primary surgery followed by adjuvant therapy is the current standard of care in the multidisciplinary management of squamous cell carcinoma (SCC) of the oral tongue. Additionally, salvage glossectomy is used to treat recurrent base of tongue SCC. Microvascular free tissue transfer reconstruction (MVFTT) is utilized to maximize functional outcomes such as swallowing. We sought to identify prognostic factors related to achievement of a total oral diet in patients that underwent glossectomy with MVFTT. METHODS: Retrospective review at a tertiary care center from 2010 to 2015. RESULTS: 200 patients (69% male, mean age 60 years) met inclusion criteria. Extent of glossectomy was categorized as partial or hemiglossectomy (39%), tongue base resection with or without hemi-oral glossectomy (23%), composite resection with mandibulectomy (18%), and subtotal or total glossectomy (21%). Flap success rate was 96%. Median follow-up time was 14  months. A total oral diet was achieved by 49% of patients with median time to achievement of 31  days (IQR 9-209). Multivariate analysis identified body mass index  < 25 kg/m2, prior radiation therapy, adjuvant chemoradiation, and resection requiring subtotal or total glossectomy or concurrent mandibulectomy as independent risk factors for worse total oral diet achievement. CONCLUSION: Swallowing dysfunction represents a significant morbidity following glossectomy in the treatment of SCC. High BMI, smaller resection fields, and absence of prior radiation therapy or adjuvant chemoradiotherapy correlated with improved likelihood of obtaining a total oral diet. Patients should be appropriately counseled of this risk with emphasis placed on aggressive swallow rehabilitation in the post- treatment setting.

Factors associated with gastrostomy tube dependence following salvage total laryngectomy with microvascular free tissue transfer.

BACKGROUND: Following salvage total laryngectomy (STL) with microvascular-free tissue transfer (MFTT), patients are at high risk for swallowing dysfunction, but risk factors for persistent gastrostomy tube (G-tube) dependence are unknown. METHODS: Retrospective review of 33 patients who underwent STL with MFTT. RESULTS: A total oral diet was achieved by 81% of patients with ≥6 months of postoperative follow-up. Approximately 27% of patients were G-tube dependent preoperatively with 67% achieving a total oral diet postoperatively. Factors associated with persistent G-tube dependence included pT4 tumor, pN2+ status, more extensive pharyngectomy, and re-irradiation. Strictures occurred in 30% of patients and were associated with more extensive pharyngectomy and tubed reconstruction. CONCLUSIONS: For patients undergoing STL with MFTT, the majority of patients achieve a total oral diet regardless of their preoperative swallowing function. Advanced-stage recurrent tumors and increased extent of pharyngectomy contribute to poorer swallowing outcomes.

Multicenter Assessment of Antibiotic Prophylaxis Spectrum on Surgical Infections in Head and Neck Cancer Microvascular Reconstruction.

Objective To characterize and identify risk factors for 30-day surgical site infections (SSIs) in patients with head and neck cancer who underwent microvascular reconstruction. Study Design Cross-sectional study with nested case-control design. Setting Nine American tertiary care centers. Subjects and Methods Hospitalized patients were included if they underwent head and neck cancer microvascular reconstruction from January 2003 to March 2016. Cases were defined as patients who developed 30-day SSI; controls were patients without SSI at 30 days. Postoperative antibiotic prophylaxis (POABP) regimens were categorized by Gram-negative (GN) spectrum: no GN coverage, enteric GN coverage, and enteric with antipseudomonal GN coverage. All POABP regimens retained activity against anaerobes and Gram-positive bacteria. Thirty-day prevalence of and risk factors for SSI were evaluated. Results A total of 1307 patients were included. Thirty-day SSI occurred in 189 (15%) patients; median time to SSI was 11.5 days (interquartile range, 7-17). Organisms were isolated in 59% of SSI; methicillin-resistant Staphylococcus aureus (6%) and Pseudomonas aeruginosa (9%) were uncommon. A total of 1003 (77%) patients had POABP data: no GN (17%), enteric GN (52%), and antipseudomonal GN (31%). Variables independently associated with 30-day SSI were as follows: female sex (adjusted odds ratio [aOR], 1.6; 95% CI, 1.1-2.2), no GN POABP (aOR, 2.2; 95% CI, 1.5-3.3), and surgical duration ≥11.8 hours (aOR, 1.9; 95% CI, 1.3-2.7). Longer POABP durations (≥6 days) or antipseudomonal POABP had no association with SSI. Conclusions POABP without GN coverage was significantly associated with SSI and should be avoided. Antipseudomonal POABP or longer prophylaxis durations (≥6 days) were not protective against SSI. Antimicrobial stewardship interventions should be made to limit unnecessary antibiotic exposures, prevent the emergence of resistant organisms, and improve patient outcomes.

Extracapsular Dissection vs Superficial Parotidectomy of Benign Parotid Lesions: Surgical Outcomes and Cost-effectiveness Analysis.

Importance: The clinical implications of extracapsular dissection over superficial parotidectomy are controversial and limited in data on cost-effectiveness. Objective: To compare extracapsular dissection with superficial parotidectomy for benign parotid tumors with respect to surgical outcomes and cost-effectiveness. Design, Setting, and Participants: This was a retrospective medical record review and cost-effectiveness analysis performed from August 2012 to November 2015 at a tertiary care institution. Adult patients (age ≥18 years) who underwent parotidectomy for benign parotid lesions were included. Exposures: Treatment by extracapsular dissection or superficial parotidectomy. Main Outcomes and Measures: Differences in postoperative complication rates and health services outcomes, including procedure time, anesthesia time, length of stay, and charges for surgeon, anesthesia, operating room, and hospital. Results: A total of 46 parotidectomies consisting of 26 extracapsular dissections and 20 superficial parotidectomies met criteria. Of the 46 patients, 33 were women. Patient ages ranged from 18 to 83 years. Lesion features were similar between groups with most being pleomorphic adenoma. Procedure time (effect size, -1.31; 95% CI, -1.93 to -0.65), anesthesia time (effect size, -1.37; 95% CI, -1.99 to -0.70), and length of stay (effect size, -0.66; 95% CI, -1.25 to -0.05) were significantly shorter for extracapsular dissection compared with superficial parotidectomy. Moreover, anesthesia (effect size, -1.55; 95% CI, -2.19 to -0.86), operating room (effect size, -1.09; 95% CI, -1.69 to -0.45), and total hospital charges (effect size, -1.13; 95% CI, -1.74 to -0.49) were significantly less for extracapsular dissection while remaining charges, including surgeon, showed no difference. Finally, facial nerve weakness, great auricular nerve dysesthesia, and other relevant postoperative complications were comparable between groups. Conclusions and Relevance: In the hands of an experienced surgeon, extracapsular dissection is a shorter, less costly, and equally safe alternative to traditional superficial parotidectomy when treating benign parotid lesions. Further follow-up is needed to ensure these perceived advantages are maintained over time.

Evolution of the anterolateral thigh free flap.

PURPOSE OF REVIEW: To review the recent literature on the evolution and advanced uses of the anterolateral thigh (ALT) free flap in reconstruction of oncologic defects of the head and neck. RECENT FINDINGS: The ALT free flap is a versatile flap that can be harvested in a chimeric fashion with independent, vascularized skin, muscle, fascia, nerve and bone. Various techniques for chimeric flap harvest and flap inset have been described for reconstruction of pharyngocutaneous, oromandibular and radical parotidectomy defects. These reports expand the indications for the ALT free flap while demonstrating good functional and aesthetic outcomes. SUMMARY: The ALT free flap remains popular for reconstruction of head and neck oncologic defects because of its versatility. Continued evolution in chimeric flap harvest techniques for pharyngocutaneous, osseous and radical parotidectomy defects highlights novel advanced reconstructive uses for the ALT free flap.

Intraoperative goal-directed hemodynamic management in free tissue transfer for head and neck cancer.

BACKGROUND: The purpose of this study was to determine the effect of algorithmic physiologic management on patients undergoing head and neck free tissue transfer and reconstruction. METHODS: Ninety-four adult patients were randomized to treatment and control groups. The blood pressure of the control group was managed consistent with contemporary standards. The treatment group was managed using an algorithm based on blood pressure and calculated physiologic values derived from arterial waveform analysis. Primary outcome was intensive care unit (ICU) length of stay. RESULTS: ICU length of stay was decreased in the treatment group (33.7 vs 58.3 hours; p = .026). The complication rate was not increased in the treatment group. CONCLUSION: The goal-directed hemodynamic management algorithm decreased the ICU length of stay. Judicious use of vasoactive drugs and goal-directed fluid administration has a role in improving perioperative outcomes for patients undergoing head and neck free tissue transfer. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1974-E1980, 2016.

Salivary gland transfer to prevent radiation-induced xerostomia: a systematic review and meta-analysis.

Salivary gland transfer (SGT) has the potential to prevent radiation-induced xerostomia. We attempt to analyze the efficacy of SGT in prevention of xerostomia and maintenance of salivary flow rates after radiation treatment (XRT). Systematic review and meta-analysis. Primary endpoint was efficacy of SGT in prevention of radiation-induced xerostomia. Secondary endpoint was change from baseline of unstimulated and stimulated salivary flow rates after XRT. Seven articles, accruing data from 12 institutions, met inclusion criteria. In a total of 177 patients at mean follow-up of 22.7months, SGT prevented radiation-induced xerostomia in 82.7% (95% CI, 76.6-87.7%) of patients. Twelve months after XRT, unstimulated and stimulated salivary flow rates rose to 88% and 76% of baseline values, respectively. In comparison to control subjects twelve months after XRT, SGT subjects' unstimulated (75% vs. 11%) and stimulated (86% vs. 8%) salivary flow rates were drastically higher in SGT patients. Salivary gland transfer appears to be highly effective in preventing the incidence of xerostomia in patients receiving definitive head and neck radiation therapy.

Thyroid disease and compressive symptoms.

OBJECTIVES/HYPOTHESIS: Compressive symptoms are common in thyroid disease, but few studies have focused on the presence, associated factors, and etiology of compressive symptoms. STUDY DESIGN: Retrospective review. METHODS: Patients who underwent thyroidectomy from 2005 through 2009 were reviewed. The data included demographics, indication for surgery, compressive symptoms, complications, diagnosis, volume of thyroid gland, presence of inflammation, and follow-up. RESULTS: Three hundred thirty-three patients were identified. The mean age was 51 years, and 82% were female. Fifty-two percent (n=172) of patients experienced compressive symptoms preoperatively, including dysphagia (n=131) and shortness of breath (n=83). Twenty-six percent (n=86) of patients presented with voice changes, and 8% (n=27) complained of odynophagia. Postoperatively, 25 patients (8%) continued to have compressive symptoms (P<.0001), and 10 patients (3%) developed new compressive symptoms. Compressive symptoms were present in 72% (n=21) of patients with lymphocytic thyroiditis, 71% (n=5) of patients with anaplastic thyroid cancer, and 60% (n=92) of patients with goiter. The average volume of the gland in patients with compressive symptoms was 75.5 mL compared to 37.1 mL in asymptomatic patients (P<.0001). There was not a significant relationship between compressive symptoms and the presence of inflammation (P=.869). CONCLUSIONS: Patients with thyroid disease frequently present with compressive symptoms, and the majority of patients experience relief postoperatively. The volume of the thyroid gland is associated with compressive symptoms along with additional contributing factors.

Surgical anatomy of the thyroid and parathyroid glands.

This article describes the anatomy and embryology of the thyroid and parathyroid glands and the recurrent laryngeal nerve, discussing how the anatomy affects function and dysfunction of the glands.

Neural outcomes after plasma knife dissection: a pathologic study and clinical correlation.

BACKGROUND: The initial aim was to determine the rate of pathologic tissue damage when dissecting the rat sciatic nerve with either bipolar forceps or low-temperature tripolar plasma knife. The second aim was to determine the safety and effectiveness of the plasma knife during parotid surgery. METHODS: A prospective, randomized, single-blind study was performed on 40 rat sciatic nerves dissected by either bipolar electrocautery with a cold knife or a plasma knife. Dissected nerves were excised and submitted blindly to pathology for analysis of nerve injury. The degree of nerve trauma was graded by the Carlander nerve injury classification. Separately, a review was performed on the facial nerve outcomes of 30 patients who underwent plasma knife parotidectomy. RESULTS: No thermal or neural injury was noted in the 40 rat sciatic nerves dissected by either bipolar electrocautery or plasma knife (p = 1.0). Two plasma knife-dissected nerves (8%) demonstrated significant numbers of mast cells in the perineural soft tissue. In 30 patients undergoing plasma knife-parotidectomy, 10 (33%) had mild weakness of 1 or 2 preserved facial nerve branch postoperatively (House-Brackmann 2) that resolved within 1 month, whereas 2 (7%) had visible weakness in 1 branch (HB 3) that normalized after 3 months of follow-up. CONCLUSION: Plasma knife nerve dissection seems to be a safe and effective alternative to conventional methods. This technique may confer some advantages over conventional methods with the ability to simultaneously cut and coagulate tissue with minimal thermal spread and electrical stimulation of adjacent neural structures.

Head and neck cancer recurrence and mortality in nonselective cyclooxygenase inhibitor users.

OBJECTIVE: To determine whether ongoing use of a cyclooxygenase (COX) inhibitor is associated with a reduction in mortality and disease recurrence after head and neck cancer treatment. DESIGN: Retrospective case-control study. Patients A total of 325 potential subjects with head and neck squamous cell carcinoma were identified using an electronic patient database. Main Outcome Measure The rate of COX inhibitor use among patients who had died or whose disease had recurred (cases) was compared with the rate of use among survivors or those without recurrence (controls). The comparison was controlled for tumor site, tumor stage, treatment received, age, sex, race, smoking, and alcohol use. RESULTS: The 325 patients were compared by logistic regressions, with recurrence rate and survival status as the dependent variables. There was no difference in COX inhibitor exposure between patients with recurrence and those with no recurrence (P = .42) or between survivors and those who died of disease (P = .66). The median survival of COX inhibitor users, however, was 96 months, compared with 47 months in nonusers. The only independent variable with a significant impact on recurrence and survival was tumor stage at the time of diagnosis. CONCLUSIONS: Although preliminary in vitro studies suggest an antitumor effect of COX inhibitors in head and neck cancer, this study found no difference in head and neck cancer recurrence or survival in nonselective COX inhibitor users vs nonusers. A randomized, double-blinded controlled trial is needed to determine if COX inhibitors are an effective chemopreventive therapy in patients with head and neck cancer.

Melanoma of the head and neck.

Staging of cutaneous melanoma has changed in recent years with an increased emphasis upon thickness and ulceration on prognosis of early stage disease. Cutaneous melanoma of the head and neck is treated with complete surgical resection in early stage disease. Resection margins are determined by the size, depth, and presence of satellite lesions. Evaluation for regional and distant metastatic disease is necessary in all cases of advanced stage disease. Sentinel lymph node biopsy and possible parotidectomy and neck dissection should be considered in head and neck cutaneous melanomas greater than 1 mm in thickness or with ulceration. Adjuvant therapy may be indicated in advanced primary, nodal, and metastatic disease. Mucosal melanoma of the head and neck remains a difficult disease to treat, with high locoregional recurrence rates and poor prognosis despite aggressive therapy.

Systematic review of intratympanic gentamicin in Meniere's disease.

OBJECTIVES: To assess and summarize the best available evidence for the use of intratympanic gentamicin in patients with Meniere's disease with respect to improvement of vertigo, tinnitus, and change in hearing. METHODS: Comprehensive electronic searches were conducted on the databases of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. All generated titles were reviewed, and potentially relevant articles were assessed for inclusion. Data from included articles were extracted and summarized. RESULTS: Overall pooled results on vertigo control revealed complete or substantial control in 89% of patients (study range 73-100%). Hearing was worsened in 26% (0-90%). Subjective improvement in tinnitus was seen in 57% of patients (0-82%). Different treatment protocols all resulted in similar rates of vertigo control. CONCLUSIONS: Intratympanic gentamicin appears effective in controlling the symptoms of Meniere's disease, regardless of the protocol used. Although the literature on this treatment is extensive, there is a likelihood of significant bias in many currently published reports. There is a clear need for a prospective, randomized, blinded, placebo-controlled trial to assess the true effectiveness of this treatment.