Revisiting age-related admission following tonsillectomy in the pediatric population.

OBJECTIVES/HYPOTHESIS: The objectives of this study were to examine patient outcomes using a 36-month age cutoff as a strict admission criterion following tonsillectomy, and review the safety and determine the plausibility of same-day discharge of children under 3 years old following tonsillectomy. STUDY DESIGN: Retrospective chart review. METHODS: A chart review of patients aged 24 to 42 months undergoing tonsillectomy over a 3-year period was conducted. Patients were stratified into <36 months and ≥ 36 months cohorts. Data collected included demographics, medical/sleep history, inpatient records, 30-day emergency department visits, and readmission data. Bivariate comparisons were made using χ2 and Wilcoxon tests for categorical and continuous variables. RESULTS: Between July 2014 and July 2017, 427 patients aged 24 to 42 months underwent tonsillectomy at our institution. Thirty-day emergency department visit, readmission, and greater-than-expected length of stay rates were 3.0% versus 3.7% (P = .75), 1.0 versus 1.8% (P = .61), and 4.7% versus 4.5% (P = 1.00) between the younger and older cohorts, respectively, with no difference in complication rates identified based on age. CONCLUSIONS: No significant difference in adverse outcomes was appreciated based on a cutoff of 36 months of age at a tertiary center over 3 years. There should continue to be ongoing studies addressing strict age-related admission criteria. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:E389-E394, 2019.

Pediatric Anaplastic Embryonal Rhabdomyosarcoma: Targeted Therapy Guided by Genetic Analysis and a Patient-Derived Xenograft Study.

Therapy for rhabdomyosarcoma (RMS) has generally been limited to combinations of conventional cytotoxic agents similar to regimens originally developed in the late 1960s. Recently, identification of molecular alterations through next-generation sequencing of individual tumor specimens has facilitated the use of more targeted therapeutic approaches for various malignancies. Such targeted therapies have revolutionized treatment for some cancer types. However, malignancies common in children, thus far, have been less amenable to such targeted therapies. This report describes the clinical course of an 8-year-old female with embryonal RMS having anaplastic features. This patient experienced multiple relapses after receiving various established and experimental therapies. Genomic testing of this RMS subtype revealed mutations in BCOR, ARID1A, and SETD2 genes, each of which contributes to epigenetic regulation and interacts with or modifies the activity of histone deacetylases (HDAC). Based on these findings, the patient was treated with the HDAC inhibitor vorinostat as a single agent. The tumor responded transiently followed by subsequent disease progression. We also examined the efficacy of vorinostat in a patient-derived xenograft (PDX) model developed using tumor tissue obtained from the patient's most recent tumor resection. The antitumor activity of vorinostat observed with the PDX model reflected clinical observations in that obvious areas of tumor necrosis were evident following exposure to vorinostat. Histologic sections of tumors harvested from PDX tumor-bearing mice treated with vorinostat demonstrated induction of necrosis by this agent. We propose that the evaluation of clinical efficacy in this type of preclinical model merits further evaluation to determine if PDX models predict tumor sensitivity to specific agents and/or combination therapies.

Early surgical intervention in type I laryngeal cleft.

OBJECTIVE: Diagnosis and treatment of type 1 laryngeal clefts remains a challenge. The purpose of this study is to determine if early surgical intervention in type I laryngeal clefts improves outcomes. METHODS: A retrospective case series was conducted at an academic tertiary care children's hospital. 18 children undergoing early (≤3 months from diagnosis) surgical intervention for type I laryngeal cleft repair between August of 2012 and December 2014. Data was compiled through a manual chart review. RESULTS: 18 children who underwent early surgical intervention for type I laryngeal cleft repair were identified for review. 14 (78%) were male and 4 (22%) were female and the average age at time of repair was 1.6 years. Most frequent presenting symptoms included dysphagia (61%) and recurrent respiratory issues (22%). Successful swallowing outcomes, defined as subjective improvement (i.e. absence of previous symptoms) per parental report in follow-up visits, +/- normal post-operative MBS (modified barium swallow) findings, was seen in 11 patients (61%). 9 patients required hospitalization for respiratory issues prior to surgical repair. Post-operatively, 4 patients still incurred an admission for respiratory reasons. CONCLUSIONS: Our series shows a success rate of 61% with early surgical intervention (≤3 months from diagnosis). A decrease in post-operative hospitalizations is appreciated.

Pediatric lingual and other intraoral lesions.

This article explores pediatric lingual and other intraoral lesions. First the embryology and anatomy of the oral anatomy is outlined. Then the article discusses infections and inflammatory diseases, congenital malformations, benign neoplasms, and malignant tumors.

Preclinical comparison of near-infrared-labeled cetuximab and panitumumab for optical imaging of head and neck squamous cell carcinoma.

PURPOSE: Though various targets have been proposed and evaluated, no agent has yet been investigated in a clinical setting for head and neck cancer. The present study aimed to compare two fluorescently labeled anti-epidermal growth factor receptor (EGFR) antibodies for detection of head and neck squamous cell carcinoma (HNSCC). PROCEDURES: Antigen specificities and in vitro imaging of the fluorescently labeled anti-EGFR antibodies were performed. Next, immunodeficient mice (n = 22) bearing HNSCC (OSC-19 and SCC-1) tongue tumors received systemic injections of cetuximab-IRDye800CW, panitumumab-IRDye800CW, or IgG-IRDye800CW (a nonspecific control). Tumors were imaged and resected using two near-infrared imaging systems, SPY and Pearl. Fluorescent lymph nodes were also identified, and all resected tissues were sent for pathology. RESULTS: Panitumumab-IRDye800CW and cetuximab-IRDye800CW had specific and high affinity binding for EGFR (K D = 0.12 and 0.31 nM, respectively). Panitumumab-IRDye800CW demonstrated a 2-fold increase in fluorescence intensity compared to cetuximab-IRDye800CW in vitro. In vivo, both fluorescently labeled antibodies produced higher tumor-to-background ratios compared to IgG-IRDye800CW. However, there was no significant difference between the two in either cell line or imaging modality (OSC-19: p = 0.08 SPY, p = 0.48 Pearl; SCC-1: p = 0.77 SPY, p = 0.59 Pearl; paired t tests). CONCLUSIONS: There was no significant difference between the two fluorescently labeled anti-EGFR monoclonal antibodies in murine models of HNSCC. Both cetuximab and panitumumab can be considered suitable targeting agents for fluorescent intraoperative detection of HNSCC.

MRSA and non-MRSA otorrhea in children: a comparative study of clinical course.

OBJECTIVE: To test the perception that post-tympanostomy tube otorrhea caused by methicillin-resistant Staphylococcus aureus (MRSA) is a more virulent disease than otorrhea caused by other pathogens by analyzing the clinical differences and disease courses in children diagnosed with otorrhea caused by MRSA bacteria vs non-MRSA bacteria. DESIGN: Retrospective review. SETTING: Tertiary children's hospital. PATIENTS: We retrospectively examined the medical records of children who presented to a tertiary children's hospital from January 1, 2003, to December 31, 2008, with otorrhea that occurred after tympanostomy tube insertion. MAIN OUTCOME MEASURES: Otorrhea culture records were used to group the 1079 patients into those whose otitis media was due to MRSA (n = 170) and those with non-MRSA otitis media (n = 909). From the non-MRSA group, we randomly selected an age-matched group of 170 and examined the differences between the MRSA and age-matched non-MRSA groups in organisms isolated by culture, demographic factors (including type of medical insurance), medical history, treatments, surgical procedures performed, audiometric data, and other admissions for infection-related illnesses. RESULTS: The overall incidence of MRSA in this series was about 16% (170 of 1079 patients). Of the 170 eligible children in each age-matched group, 135 with MRSA otorrhea and 141 with non-MRSA otorrhea had data in every category selected for statistical analysis. The groups did not differ significantly in type of insurance; history of tympanostomy tube placement, cholesteatoma, or prematurity; number or type (minor/major) of surgical procedures performed; or risk of subsequent infection-related diagnoses. More patients in the MRSA group received intravenous antibiotic therapy (11% vs 3.6%; P < .001). CONCLUSION: In this study, a diagnosis of otorrhea due to MRSA did not carry an increased risk for surgical procedures or infection-associated sequelae compared with a diagnosis of non-MRSA otorrhea.

Minimally invasive parathyroidectomy: use of intraoperative parathyroid hormone assays after 2 preoperative localization studies.

OBJECTIVES: To review minimally invasive parathyroidectomy (MIP) in patients undergoing initial surgical management of primary hyperparathyroidism (HPT) with preoperative, localizing sestamibi scanning (MIBI), and concordant ultrasonography (US) to determine if intraoperative parathyroid hormone (iPTH) is necessary in these cases. Minimally invasive parathyroidectomy has become an acceptable therapeutic option in treating primary HPT. Preoperative MIBI scanning, high-resolution US with color Doppler flow, and iPTH monitoring have refined this technique. DESIGN: Retrospective review. PATIENTS: The medical records of 738 consecutive patients who had undergone surgery for HPT. After excluding revision surgical procedures, secondary and tertiary HPT, unavailable intraoperative parathyroid (PTH) data, concomitant thyroid disease requiring thyroidectomy, and patients without preoperative MIBI or US, 428 patients (58%) were included in the study. RESULTS: The mean decrease in PTH level was 85%. Of the 428 patients with primary HPT included in the study, 209 patients (49%) had localizing, concordant preoperative MIBI and US. A decline of more than 50% in iPTH levels was observed in 202 patients (97%) after removal of parathyroid tissue localized by MIBI and US. The procedures for 4 patients were converted to bilateral neck explorations after the postexcision PTH level failed to drop less than 50%. CONCLUSIONS: Our results show that iPTH monitoring may be eliminated in MIP surgery in a carefully selected group of patients who have preoperative, localizing MIBI with concordant US. This potentially allows an increase in operating room efficiency and a decrease in costs while performing MIP.

Functional outcomes after transoral robotic surgery for head and neck cancer.

OBJECTIVE: To evaluate functional outcomes following transoral robotic surgery for head and neck cancer. STUDY DESIGN: Case series with planned data collection. SETTING: Academic hospital. SUBJECTS AND METHODS: Between March 2007 and December 2008, 54 of 62 candidate patients underwent transoral robotic tumor resection. Outcomes include airway management, swallowing (MD Anderson Dysphagia Inventory), and enterogastric feeding. RESULTS: Tumors were most commonly oropharynx (61%) or larynx (22%) and T1 (35%) or T2 (44%). Many received radiotherapy (22% preoperatively, 41% postoperatively) and chemotherapy (31%). Endotracheal intubation was retained (22%) for up to 48 hours, tracheostomy less frequently (9%), and all were decannulated by 14 days. Most commenced oral intake prior to discharge (69%) or within two weeks (83%). A worse postoperative Dysphagia Inventory score was associated with retained feeding tube (P=0.020), age>60 (P=0.017), higher T stage (P=0.009), laryngeal site (P=0.017), and complications (P=0.035). At a mean 12 months' follow-up, 17 percent retained a feeding tube (9.5% among primary cases). Retained feeding tube was associated with preoperative tube requirement (P=0.017), higher T stage (P=0.043), oropharyngeal/laryngeal site (P=0.034), and recurrent/second primary tumor (P=0.008). Complications including airway edema (9%), aspiration (6%), bleeding (6%), and salivary fistula (2%) were managed without major sequelae. CONCLUSION: Transoral robotic surgery provides an emerging alternative for selected primary and salvage head and neck tumors with low morbidity and acceptable functional outcomes. Patients with advanced T stage, laryngeal or oropharyngeal site, and preoperative enterogastric feeding may be at increased risk of enterogastric feeding and poor swallowing outcomes.

Revision septoplasty.

This article addresses the challenge of persistent nasal airway obstruction following septoplasty, specifically as it relates to revision septoplasty. Emphasis is on the importance of and the steps to be taken in making a complete and correct diagnosis of the problem before any surgery is performed. The authors present two categories of revision surgery: surgery involving the cartilaginous septum and surgery involving the bony septum, because they believe the evaluation and management of these areas are distinct. This article presents a discussion of airflow dynamics, options to objectively assess nasal volume and patency, examination of the septum, and surgical approaches and techniques.

Role of microvascular density in nonlocalizing parathyroid sestamibi scans.

OBJECTIVES: Sestamibi scans for localization of abnormal parathyroid glands in patients with hyperparathyroidism are widely used at many institutions. Minimally invasive parathyroid surgery demands accurate preoperative localization imaging; however, nonlocalizing sestamibi scans occur in 15% of patients with primary hyperparathyroidism. It remains unknown why some sestamibi scans fail to localize. We hypothesize that an increase in microvascular density (MVD) within an adenoma will result in rapid tracer washout and a subsequent nonlocalizing scan. This study investigates the role of MVD in sestamibi localization. STUDY DESIGN: Retrospective chart review with immunohistochemical staining and data analysis. METHODS: Medical records of 83 patients who had a sestamibi scan for evaluation of primary hyperparathyroidism and underwent initial parathyroidectomy from 2000 to 2002 were retrospectively reviewed. Patients' age, sex, preoperative imaging results, operative procedure, gland weight, and histologic findings were collected. Immunohistochemistry was performed to assess MVD. RESULTS: Of the 75 preoperative sestamibi scans used, 51 patients had a localizing scan, and 24 were nonlocalizing. Localizing sestamibi scans for primary hyperparathyroidism demonstrated a sensitivity of 94% and specificity of 85%. By identifying multiglandular hyperplasia, nonlocalizing sestamibi scans produced a sensitivity of 83%. The localizing group had a greater percentage of solitary adenomas (94%) compared with the nonlocalizing group (15.6%) (P < .001). The mean gland weight for the nonlocalizing group was less than 398 g compared with the localizing groupweight of 1,113 g (P < .001). The mean MVD for localizing scan group was 229 vessels per high-power field,and the mean for the nonlocalizing scans was 213 vessels per high-power field (P = .2). CONCLUSIONS: MVD does not predict whether sestamibi scans are localizing or nonlocalizing.

Sensitivity and specificity of fluorescent immunoguided neoplasm detection in head and neck cancer xenografts.

OBJECTIVES: To determine whether fluorescently labeled anti-epidermal growth factor (EGFR) antibody could be used to detect residual disease and to guide surgical resections by comparing the sensitivity and specificity of optical fluorescence imaging with the sensitivity and specificity of histopathologic evaluation. DESIGN: A preclinical model of head and neck squamous cell carcinoma. SUBJECTS: Mice xenografted with SCC-1 tumor cells. INTERVENTIONS: The mice underwent systemic injection with anti-EGFR antibody (cetuximab) conjugated to an optically active fluorophore (Cy5.5). Both a subcutaneous flank model (n = 18) and an orthotopic murine model (n = 15) were used to assess for the presence of residual disease by fluorescent stereomicroscopy after subtotal resections of tumors. Histologic analysis was performed to confirm the presence or absence of disease. RESULTS: In the subcutaneous flank model, a diagnostic dose (50 microg) and therapeutic dose (250 microg) of fluorescent-labeled anti-EGFR were administered. When a diagnostic dose was given, the sensitivity was 86%, which was less than the 91% sensitivity when the higher dose was given. Tumor biopsy specimens in which disease was detected by histologic analysis but not by fluorescence (false-negative result) averaged 166 cells (range, 50-350 cells). The specificity of optical fluorescence to predict the presence of tumor in both groups was 100%. In the floor of the mouth model, we demonstrated a sensitivity of 81% and a specificity of 100%. False-negative results were obtained in a tumor fragment measuring less than 0.5 mm in diameter. CONCLUSION: These data support further investigation of fluorescently labeled anti-EGFR antibody to detect disease in the surgical setting.

Use of fluorescent labeled anti-epidermal growth factor receptor antibody to image head and neck squamous cell carcinoma xenografts.

Physicians and surgeons rely on subtle tissue changes to detect the extent of tumors and the presence of residual disease in the clinical setting. The development of a cancer-specific fluorescent contrast agent has the potential to provide real-time tumor imaging in the clinic or operating room. Because epidermal growth factor receptor (EGFR) is highly overexpressed on the surface of head and neck squamous cell carcinoma (HNSCC), we sought to determine if fluorescently labeled anti-EGFR antibody could be used to image HNSCC xenografts in vivo. Cetuximab or control isotype-matched IgG1 was conjugated with the Cy5.5 fluorochrome and systemically injected into mice bearing human split thickness skin grafts, tumor cell line xenografts, transplanted human tumor xenografts, or mouse mesothelioma tumors. Xenografts were imaged by time-domain fluorescence imaging or fluorescence stereomicroscopy. Both imaging modalities detected specific uptake of cetuximab-Cy5.5 in HNSCC xenografts with significantly higher fluorescence levels relative to control IgG1-Cy5.5. Tumor xenograft fluorescence was higher compared with background (before injection), human split thickness skin grafts, or mouse mesothelioma tumors at 24, 48, and 72 h. Fluorescence was detected in multiple HNSCC tumor cell lines with variable EGFR expression levels. Mock resections of flank tumors using fluorescence stereomicroscopy showed that small (2 mm) specimens could be detected in the surgical wound bed. These results show the feasibility of using fluorescently labeled anti-EGFR antibody to detect human tumors in the surgical setting.

In vivo detection of head and neck cancer orthotopic xenografts by immunofluorescence.

PURPOSE: To determine whether Cy5.5-labeled antiepidermal growth factor (EGFR) antibody could be used to detect head and neck squamous cell carcinoma (HNSCC) xenografts in vivo. METHODS: AntiEGFR antibody (cetuximab) was labeled with Cy5.5, a fluorophore with emission in the near infrared range. The cetuximab-Cy5.5 conjugate was systemically administered in subtherapeutic doses (50 microg) to mice bearing orthotopically xenografted HNSCC cell lines (SCC1, CAL27, and FaDu). As a control, isotype-matched human immunoglobulin (Ig)G1k antibody labeled with Cy5.5 was systemically injected in parallel experiments. All tumor regions (n = 6) were imaged by fluorescent stereomicroscopy at 0, 6, 24, 48, or 72 hours. Tumor size was measured by high-frequency ultrasonography at 72 hours. Transcervical partial and near-total resections were then performed with stereomicroscopic imaging after each resection. The mandible and associated structures were then resected, paraffin embedded, and then serial sectioned for analysis. RESULTS: Tumors could be clearly visualized by near infrared fluorescent stereomicroscopy at 48 and 72 hours after systemic administration of cetuximab-Cy5.5 but not after administration with the labeled isotype control antibody, IgG1k-Cy5.5. Ultrasound measurement of tumors (n = 5) correlated with fluorescent measurements of tumor (Spearman's coefficient, 0.92, P

Pretreatment, preoperative swallowing exercises may improve dysphagia quality of life.

OBJECTIVES: Dysphagia is commonly associated with head and neck cancer treatment. Traditional dysphagia management strategies focus on post-treatment therapy. This study evaluated the utility of pretreatment swallowing exercises in improving post-treatment swallowing quality of life (QOL). STUDY DESIGN: Prospective cohort study and cross-sectional QOL analysis. METHODS: This study includes 37 patients who underwent primary radiation or combined chemoradiation treatment for newly diagnosed hypopharyngeal, laryngeal, or oropharyngeal primary tumors at the University of Alabama at Birmingham. Of the 37, 25 patients underwent swallowing exercises beginning 2 weeks prior to the start of radiation. The M.D. Anderson Dysphagia Inventory (MDADI) was administered an average of 14 months after treatment to assess the success of the protocol. Analysis of QOL scores related to gender, primary site, stage, and race were obtained. RESULTS: Patients who performed pretreatment swallowing exercises (n = 25) showed improvement in the overall MDADI score (P = .0002) compared to the control population (n = 12) who underwent post-treatment therapy. Furthermore, a separate analysis of individual domains of the MDADI (global, emotional, functional, and physical) demonstrated improved quality of life. CONCLUSIONS: Implementation of pretreatment swallowing education and exercise may improve dysphagia-specific QOL in head and neck cancer patients undergoing radiation and/or chemoradiation therapy.

High-risk tracheostomy: exploring the limits of the percutaneous tracheostomy.

OBJECTIVES: Modifications of the percutaneous tracheostomy (PercTrach) technique have made this a straightforward and safe procedure in appropriately selected patients. We sought to determine its value in high-risk patients. STUDY DESIGN/METHODS: A retrospective study of high-risk and low-risk patients on whom bedside PercTrach was performed between May 2003 and October 2004 at the Medical College of Georgia. The patients were prospectively stratified into groups based on their comorbidities (morbid obesity or coagulopathy). The Ciaglia Blue Rhino introducer set was used in all cases. RESULTS: Fifty-four consecutive patients were included in the study; the high-risk patients (n = 16) were younger than the low-risk (n = 38) patients (48.2 vs. 53.6 years, respectively), but had significantly higher Acute Physiology and Chronic Health Evaluation II scores (10.1 vs. 5.4, P = .0001). There were seven morbidly obese patients with a mean body mass index of 64.4 and a mean weight of 184.9 kg. There were 9 patients with a total of 10 coagulopathic conditions (7 = International Normalized Ratio [INR] of >1.5, 2 = heparin drip, 1 = platelet count < 20,000). One patient included in the study met requirements for two categories with a platelet count of 17,000 and an INR of 1.7. The procedural times ranged from 5 to 30 minutes. The high-risk PercTrachs took 14.4 +/- 5.0 minutes on average, compared with 12.2 +/- 4.8 minutes in the low-risk group (P = .115). One patient in the low-risk group bled from an anterior jugular communicating vein injury, requiring wound exploration and vein ligation. There were no other significant complications. CONCLUSIONS: There were no statistically significant differences in intraoperative or perioperative outcomes between the PercTrachs performed in high-risk versus low-risk patients. PercTrachs may be performed safely even in high-risk patients such as those with morbid obesity and coagulopathy.