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James L Netterville

Publications and source records attributed to James L Netterville.

At least 19 recordsLinked to original sources
PubMed2026

An integrated single-cell and spatial transcriptomic atlas of thyroid cancer progression identifies prognostic fibroblast subpopulations.

Although well-differentiated thyroid carcinoma (WDTC) is characterized by a robust treatment response, aggressive subtypes, such as anaplastic thyroid carcinoma (ATC), remain highly lethal. To understand thyroid cancer evolution in both children and adults, we analyzed single-cell transcriptomes of 423,733 cells from 81 samples and spatially resolved key tumor and microenvironment populations across 28 tumors with spatial transcriptomics, including rare and unique composite WDTC/ATC tumors and pediatric diffuse sclerosing thyroid carcinomas. Additionally, we identified gene signatures of stromal cell populations in 5 large thyroid cancer bulk RNA-sequencing cohorts. Through this multi-institutional effort, we defined a population of POSTN+ myofibroblast cancer-associated fibroblasts (myCAFs) that are intimately associated with invasive tumor cells and correlate with poor prognosis, lymph node metastasis, and disease progression in thyroid carcinoma. We also revealed a population of inflammatory CAFs that are distant to tumor cells and are found in the inflammatory stromal microenvironment of autoimmune thyroiditis. Together, our study provides spatial profiling of thyroid cancer evolution in samples with mixed WDTC/ATC histopathology and identifies a prognostic myCAF subtype with potential clinical utility in predicting aggressive disease in both children and adults.

Humans↗
PubMed2006

Carotid body tumor resection: does the need for vascular reconstruction worsen outcome?

We evaluated outcomes after carotid body tumor resection (CBR) requiring vascular reconstruction. Patients undergoing CBR at an academic medical center between 1990 and 2005 were identified. Medical records were retrospectively reviewed for clinical data, operative details, Shamblin's classification, tumor pathology, complications, and mortality. Comparisons were performed between those undergoing CBR alone and CBR requiring vascular reconstruction (CBR-VASC). Of the 71 CBRs performed in 62 patients, 16 required vascular reconstruction (23%). Although there was no difference in mean tumor size (CBR 29.1 +/- 11.9 mm, CBR-VASC 32.5 +/- 9.9 mm; p = 0.133), carotid body tumors were more commonly Shamblin's I when CBR was performed alone (CBR 53% vs. CBR-VASC 25%, p = 0.045) and Shamblin's II/III when vascular reconstruction was required (CBR 47% vs. CBR-VASC 75%, p = 0.045). There was also a significant difference in malignant tumor pathology when vascular reconstruction was required (CBR 4.4% vs. CBR-VASC 25%, p = 0.034). Cranial nerve dysfunction was higher in patients requiring vascular repair (CBR 27% vs. CBR-VASC 63%, p = 0.012), but there was no difference in baroreflex failure (CBR 7.27% vs. CBR-VASC 0%, p = 0.351), Horner's syndrome (CBR 5.5% vs. CBR-VASC 6.25%, p = 0.783), or first bite syndrome (CBR 7.27% vs. CBR-VASC 12.5%, p = 0.877). There were no perioperative strokes in either group, and one death was unrelated to operation. When required, carotid artery reconstruction at the time of CBR can be performed safely. Although cranial nerve dysfunction is more common when vascular repair is required, this is more likely related to locally advanced disease and tumor pathology rather than operative techniques.

Academic Medical Centers↗
PubMed2006

Gene expression differences associated with human papillomavirus status in head and neck squamous cell carcinoma.

Human papillomavirus (HPV) is associated with a subset of head and neck squamous cell carcinoma (HNSCC). Between 15% and 35% of HNSCCs harbor HPV DNA. Demographic and exposure differences between HPV-positive (HPV+) and negative (HPV-) HNSCCs suggest that HPV+ tumors may constitute a subclass with different biology, whereas clinical differences have also been observed. Gene expression profiles of HPV+ and HPV- tumors were compared with further exploration of the biological effect of HPV in HNSCC. Thirty-six HNSCC tumors were analyzed using Affymetrix Human 133U Plus 2.0 GeneChip and for HPV by PCR and real-time PCR. Eight of 36 (22%) tumors were positive for HPV subtype 16. Statistical analysis using Significance Analysis of Microarrays based on HPV status as a supervising variable resulted in a list of 91 genes that were differentially expressed with statistical significance. Results for a subset of these genes were verified by real-time PCR. Genes highly expressed in HPV+ samples included cell cycle regulators (p16(INK4A), p18, and CDC7) and transcription factors (TAF7L, RFC4, RPA2, and TFDP2). The microarray data were also investigated by mapping genes by chromosomal location (DIGMAP). A large number of genes on chromosome 3q24-qter had high levels of expression in HPV+ tumors. Further investigation of differentially expressed genes may reveal the unique pathways in HPV+ tumors that may explain the different natural history and biological properties of these tumors. These properties may be exploited as a target of novel therapeutic agents in HNSCC treatment.

Adult↗
PubMed2006

Revision lateral skull base surgery.

OBJECTIVE: To describe functional and reconstructive results after revision lateral skull base surgery with comparison of benign and malignant lesions. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: All patients undergoing revision surgery for benign and malignant lateral skull base tumors. INTERVENTIONS: Surgical resection of recurrent lateral skull base tumors and reconstruction of resulting defects. MAIN OUTCOME MEASURES: Cranial nerve function postoperative complications. RESULTS: Forty operations for recurrent lateral skull base tumors occurred between January 1, 1987, and December 31, 2003, with follow-up of at least 1 year. Thirty-three operations were for benign lesions, 27 of which were glomus tumors. Seven operations were for malignant tumors. Fifty-eight percent of patients had preoperative cranial nerve deficits (66% of benign tumors and 14% of malignancies). The most common preoperative deficit occurred in the Xth cranial nerve. Postoperative cranial nerve deficits were seen in 95% of patients and multiple nerve deficits were seen in 75%. The most common postoperative deficits were observed in the IXth and Xth cranial nerves. Thirty-one patients had one previous procedure, six had two previous procedures, and three had three previous procedures. Abdominal fat and temporoparietal fascia were the most common reconstruction materials. There was one case of meningitis, two cerebrospinal fluid leaks, and one pseudomeningocele. There was one recurrent adenoid cystic tumor resulting in death and two partially resected glomus tumors. Subsequent procedures are discussed. CONCLUSION: Postoperative cranial deficits are more common after revision skull base surgery than after primary surgery. Complete resection without recurrence can be expected for revision skull base surgery. Modern reconstruction techniques reduce major postoperative complications and morbidity from cranial nerve deficits.

Adolescent↗
PubMed2006

Laryngoscopy in bilateral vocal fold immobility: can you make a diagnosis?

OBJECTIVES: This study explores whether videoendoscopic findings and patient history help make the diagnosis in bilateral vocal fold immobility (BVFI). METHODS: Medical records from 1995 to 2003 were searched to identify patients with posterior glottic stenosis (PGS) and bilateral vocal fold paralysis (BVFP) who also had videoendoscopic examinations. Videoendoscopic examination findings that could help differentiate PGS from BVFP were identified a priori. A weighted scoring index, based on the adjusted odds ratios of significant examination findings on multiple logistic regression, was derived. Associations between the weighted scoring index, patient history, and diagnosis were then evaluated. RESULTS: Twenty-six patients with BVFP and 28 patients with PGS were identified. Posterior glottic scar (weight = 2), medial arytenoid erosion with a widened posterior glottis (weight = 1), and appropriate vocal fold motion (weight = 1) were significant variables (p < or = .05, multiple logistic regression) and constituted the weighted scoring index. A weighted scoring index of > or = 2 and a history of prolonged intubation predicted PGS in 95.2% of cases. A weighted scoring index of < or = 1 and a history of neck surgery predicted BVFP in 95.0% of cases. CONCLUSIONS: The weighted scoring index with the patient history provides an objective tool for diagnosing BVFI.

Adult↗
PubMed2006

Pedicled fat flap reconstruction of the atrophic or "empty" paraglottic space following resection of teflon granuloma or oversized implant.

OBJECTIVES: Loss of functional and supporting architecture in the paraglottic space (PGS) necessitates augmentation to restore phonation and prevent aspiration. Our previous PGS reconstructions using an inferiorly based sternohyoid muscle flap have shown a propensity to fibrose over time, tethering the vocal fold inferolaterally. Poor voice outcomes have led us to explore other reconstructive options such as the laterally based vascularized fat flap described below. Our objectives in the present study were 1) to discuss phonosurgical options for reestablishing PGS volume after removal of an oversized implant or after definitive resection of Teflon granuloma; and 2) to understand the surgical technique, indications, and functional prognosis of the laterally based fat flap used for augmenting the "e mpty" PGS. Fourteen cases of PGS reconstruction with a laterally based subplatysmal fat flap were retrospectively investigated for indications, functional outcome, and the need for subsequent phonosurgical procedures. Preoperative and postoperative voice and videostroboscopic findings were analyzed. RESULTS: Fat flap augmentation helped achieve subjective vocal improvement in patients with an empty PGS. A subset of our patients demonstrated fat flap atrophy within 12 months, prompting revision laryngoplasty. Viable flaps were encountered in each revision, facilitating future medialization attempts. CONCLUSIONS: Fat flap reconstruction of the PGS is a versatile, beneficial adjunct for revision medialization in select cases.

Adipose Tissue↗
PubMed2005

Surgical management of parapharyngeal space masses.

BACKGROUND: We sought to examine surgical techniques used to remove parapharyngeal space (PPS) masses. METHODS: This retrospective search was conducted from 1980 to 2003. Age, sex, diagnosis, surgical approach, complications, and outcome were collected. RESULTS: One hundred sixty-six PPS masses were identified: 21 (12.7%) were malignant, 145 (87.3%) were benign, 76 (45.8%) were vascular, and 69 (41.6 %) involved the skull base. Transcervical techniques were used in all cases. Removing the styloid and its musculature and level II lymphadenectomies enhanced exposure for vascular and skull base tumors. Thirty transcervical-transmastoid dissections (20.4%) facilitated removal of vascular skull base tumors. To identify the facial nerve, 20 transparotid-transcervical approaches (13.6%) were performed. Three mandibulotomies (2.0%) were required for internal carotid artery involvement. Expected neurologic sequelae resulted from cranial nerve involvement by tumor. Three patients (2.0%), all presenting with recurrent cancer, had local recurrences. CONCLUSION: Careful patient assessment and surgical techniques allow the oncologically safe removal of benign, vascular, and skull base PPS tumors.

Adolescent↗
PubMed2005

Cervicofacial and cervicothoracic rotation flaps in head and neck reconstruction.

BACKGROUND: Compound cervicofacial and cervicothoracic rotation flaps are highly versatile flaps that may be applied to a variety of defects of the cheek, orbit, periauricular region, and neck. These rotation advancement flaps should be a staple of the head and neck surgeon's reconstructive armamentarium. METHODS: This is a retrospective review of medical records at a university-based head and neck cancer center. RESULTS: Thirty-three patients were identified, with a mean age of 66 years. Primary or recurrent skin neoplasms made up the most common indication for surgery, followed by primary parotid tumors and cervical lymphatic metastases from upper aerodigestive tract malignancies. Defects of the cheek, orbit, periauricular region, and neck were reconstructed with cervicofacial or cervicothoracic flaps, with larger wounds requiring variable extension of the incision onto the chest wall. Other reconstructive modalities were used in 18 cases to increase tissue bulk or provide internal lining. Minor wound complications occurred in 13 patients. There was no statistically significant association between wound complications and smoking or previous radiation therapy. CONCLUSIONS: Compound cervicofacial and cervicothoracic rotation flaps provide a straightforward, reliable, and efficient means to reconstruct complex defects of the face, lateral skull base, and neck, with the potential for excellent cosmetic results.

Adult↗
PubMed2005

Anatomic study of laser-assisted endoscopic cricopharyngeus myotomy.

OBJECTIVES: Laser-assisted endoscopic cricopharyngeus muscle (CPM) myotomy has been used to correct dysphagia caused by CPM dysfunction. The aim of this study was to anatomically characterize this procedure in hopes of demonstrating its safety and efficacy. METHODS: A Dohlman endoscope was used to isolate the CPM in 5 lightly preserved, thawed cadavers. A carbon dioxide laser at 10 W continuous power was used to section through the CPM in conjunction with a micromanipulator connected to an operating microscope. The specimens were then carefully dissected and photographed to demonstrate the anatomy of the pharyngoesophageal segment, including the location of the incision and the condition of the tissue planes. The CPM was harvested for histologic studies, sectioned, and prepared with modified Gomori trichrome stain. RESULTS: Gross examination of the retropharyngeal region revealed the presence of intact buccopharyngeal fascia between the lasered region and the retropharyngeal space. Histologic analysis demonstrated sectioning of the CPM with preservation of this fascia layer. Placement of the endoscope was difficult in 1 cadaver, in which we were unable to properly identify the CPM. CONCLUSIONS: The carbon dioxide laser-assisted endoscopic CPM myotomy is a potentially anatomically safe and viable procedure when properly performed. However, the potential for violation of the retropharyngeal space is real.

Cadaver↗
PubMed2004

Paragangliomas of the head and neck.

Paragangliomas are neuroendocrine tumors derived from the extra-adrenal paraganglia of the autonomic nervous system. Within the head and neck, they are generally defined and named according to their site of origin, and may be found frequently neighboring vascular structures. Physiologic activity is rare in these neoplasms and they may exhibit patterns of inheritance which predispose their occurrence in families, often with multicentricity. These tumors generally exhibit a slow rate of growth, most often presenting asymptomatically as a space occupying mass lesion noted clinically or radiographically. The most common paraganglioma of the head and neck is the carotid body tumor followed by the jugulo-tympanic and vagal varieties. Other rare sites where this tumor may occur include; the larynx, sinonasal chambers and orbit. Diagnosis is generally made through a combination of clinical findings and radiographic studies. Magnetic resonance represents the most important imaging modality for the evaluation and characterization of suspected head and neck paraganglioma. Definitive management for these lesions should be carefully considered in relation to both tumor and patient-oriented factors, especially in regard to the potential morbidity of treatment. Surgery and radiation therapy represent the main treatment modalities for paraganglioma. The selection of treatment depends on the size, location, and biologic activity of the tumor as well as the overall fitness of the patient. Although radiotherapy may be effective in arresting growth of these tumors, rarely is the neoplasm eliminated without surgical resection. Surgery may be associated with significant morbidity, primarily as a consequence of incurring major cranial nerve injury. Patient selection (relative to age and medical condition) should be carefully considered prior to recommending aggressive surgery for paragangliomas of head and neck, especially in those patients at risk for disabling surgical morbidity.

Carotid Body Tumor↗
PubMed2004

Carbon dioxide laser endoscopic diverticulotomy versus open diverticulectomy for Zenker's diverticulum.

OBJECTIVES/HYPOTHESIS: To compare open and CO2 laser-assisted endoscopic surgical management of Zenker's diverticulum. STUDY DESIGN: A retrospective review of 49 consecutive surgically treated patients with Zenker's diverticulum was conducted. METHODS: Patients' records were reviewed and analyzed for patient age and sex, size of diverticulum, incision time (time recorded from start of incision to surgical completion of case), length of hospital stay, complications, and follow-up management. A postoperative questionnaire inquiring about swallow function was conducted by mail or telephone. Swallow function was assessed on a four-point scale. RESULTS: Various procedures performed included endoscopic CO2 laser-assisted diverticulotomy (n = 24) and open diverticulectomy with cricopharyngeal myotomy (n = 28). The average incision time of laser endoscopic cases (47 min) was significantly shorter (P <.001) than that of open diverticulectomy cases (170 min). Length of hospital stay did not significantly vary between the two groups. Five patients (21%) initially treated with laser endoscopic diverticulotomy demonstrated symptomatic persistent Zenker's diverticulum; three underwent repeat operation. No open cases required repeat operation. One endoscopic case was aborted secondary to esophageal injury from placement of the endoscope. Postoperative fever was seen in two (8%) endoscopic cases and four (14%) open approach cases. No major complications (recurrent laryngeal nerve paralysis, mediastinitis, or death) were encountered. More than 90% of respondents in each treatment group reported normal or near-normal swallow function. CONCLUSION: Laser endoscopic management is a reasonable and safe method for surgical treatment of Zenker's diverticulum in comparison with the open technique. Employment of the endoscopic approach reduces operative time and the complexity of postoperative care. Practitioners should be aware that the endoscopic approach may result in a higher failure rate.

Aged↗
PubMed2004

Tumors of the accessory lobe of the parotid gland: a 10-year experience.

OBJECTIVES/HYPOTHESIS: The differential diagnosis of midcheek masses include pathology arising from normal anatomic structures or from variations of normal accessory parotid gland tissue. Accessory parotid gland tissue has been described as salivary tissue adjacent to Stenson's duct that is separate from the main body of the parotid gland. We report our 10-year experience with the diagnosis and treatment of eight accessory parotid gland neoplasms that have been followed by the senior authors. STUDY DESIGN: This is a retrospective review of our experience with eight accessory parotid gland neoplasms. METHODS: A literature review and retrospective chart review of our experience with accessory parotid gland tumors over the past 10 years. The presentation, evaluation, management, treatment, and outcome were recorded. RESULTS: Eight cases of accessory lobe parotid tumors were identified, which have been followed since the date of initial treatment. All of the patients presented with a slowly growing cheek mass. There was one case of carcinoma expleomorphic adenoma, one case of undifferentiated carcinoma (small cell carcinoma), one case of basal cell adenocarcinoma, one case of benign salivary cyst, two cases of pleomorphic adenoma, and two cases of monomorphic adenoma. A standard facelift approach or modified Blair incision was used to excise these tumors. CONCLUSIONS: Neoplasms of the accessory parotid gland are rare. Management of these tumors include a high index of suspicion, good understanding of the anatomy, and meticulous surgical approach.

Adult↗
PubMed2003

Palatal reconstruction with the palatal island flap.

OBJECTIVES/HYPOTHESIS: The management of palatal defects resulting from the extirpation of benign and malignant lesions uses a variety of methods, with the optimal techniques allowing maximal postoperative function with minimal morbidity. The palatal island flap is an effective, reliable technique for reconstructing postablative oral cavity defects. METHODS: All patients who underwent palatal resections for benign or malignant lesions at a tertiary care, referral-based head and neck cancer center since 1995 were eligible. Ten patients were identified whose surgical defects were reconstructed with palatal island flaps. The cases were reviewed for the symptomatology, tumor features, defect size, perioperative and postoperative management, complications, and impact on palatal function. RESULTS: Ten patients ranging in age from 18 to 81 years underwent palatal island mucoperiosteal flaps after resection of a variety of benign and malignant tumors, most arising from minor salivary glands. The defects ranged in size from 5 to 15 cm2, with extension into the floor of the nose in four cases and to the skull base in two. Nine patients were discharged on a regimen of oral diet, and no patient manifested permanent velopharyngeal insufficiency, speech impairment, or airway compromise. Follow-up ranged from 3 months to 6 years, with an average follow-up of 18.5 months. Delayed donor site re-epithelialization required debridement in one case, and two patients required obturation of small oronasal fistulae. CONCLUSION: The palatal island mucoperiosteal flap provides an effective means of reconstructing hard and soft palate defects with few complications and low morbidity.

Adolescent↗
PubMed2003

Reanimation of the paralyzed human larynx with an implantable electrical stimulation device.

OBJECTIVES/HYPOTHESIS: Electrical stimulation of the posterior cricoarytenoid muscle, when paced with inspiration, offers a physiological approach to restore ventilation in bilateral laryngeal paralysis without any of the disadvantages associated with conventional treatment. STUDY DESIGN: A prospective study of six patients. METHODS: The patients were successfully implanted with an Itrel II stimulator (Medtronic, Inc). In postoperative sessions, stimulated vocal fold abduction, patient ventilation, and voice were assessed and compared with preoperative values. RESULTS: The optimum stimulus paradigm was a 1- to 2-second train of 1-millisecond pulses delivered at a frequency of 30 to 40 Hz and amplitude of 2 to 7 V. Posterior cricoarytenoid stimulation produced a large dynamic abduction (3.5-7 mm) in three patients and moderate abduction (3 mm) in a fourth patient. The fifth patient showed a large but delayed response of 4 mm to stimulation with some lateralization of the vocal fold. In the sixth patient, stimulated abduction was noted on device implantation but was lost postoperatively. All five patients with stimulated abduction postoperatively met the ventilatory criteria for decannulation, and three patients subsequently had decannulation. Long-term stimulation of the posterior cricoarytenoid muscle had no appreciable effect on voice quality. CONCLUSIONS: Electrical stimulation of the posterior cricoarytenoid muscle shows potential as an improved therapy for bilateral vocal fold paralysis.

Adult↗
PubMed2002

Analysis of cell-cycle checkpoint pathways in head and neck cancer cell lines: implications for therapeutic strategies.

OBJECTIVE: To determine the mechanism of action of paclitaxel (Taxol) and carboplatin in cell lines of head and neck squamous cell carcinoma (HNSCC). DESIGN: Four HNSCC cell lines were treated with paclitaxel and carboplatin, alone or in combination, and evaluated for cell-cycle position by means of flow cytometry, for molecular determinants of cell cycle by means of Western blotting and kinase analysis, and for anchorage-independent growth by means of soft-agar assays. RESULTS: Paclitaxel was more effective at inducing apoptosis and inhibiting anchorage-independent cell growth, compared with carboplatin. The activity of paclitaxel was correlated with an elevation of cyclin B1/CDC2 activity, prolonged mitotic arrest, and Bcl-2 phosphorylation. In contrast, carboplatin arrested cells before mitosis. Combination treatment with both agents, simultaneously or sequentially, was more effective at inhibiting cell growth than either single agent. Cellular outcome was the same regardless of which drug was used first. The order of addition of these 2 drugs differentially affected cell-cycle position. Paclitaxel pretreatment arrested cells in mitosis, whereas carboplatin pretreatment or cotreatment resulted in premitotic arrest. CONCLUSIONS: To our knowledge, this study is the first to explore how paclitaxel and carboplatin, alone or in combination, differentially affect cell-cycle checkpoint response and HNSCC cell growth. These results provide molecular validation for the current clinical use of both drugs in combination and set the stage for analyses of patient tumor specimens.

Antineoplastic Agents↗
PubMed2002

Palatal adhesion: the treatment of unilateral palatal paralysis after high vagus nerve injury.

BACKGROUND: Resection of skull base tumors commonly necessitates intraoperative sacrifice of lower cranial nerves at the level of the jugular foramen. Sequelae of unilateral vagus nerve loss include ipsilateral laryngeal paralysis, ipsilateral palatal and pharyngeal paralysis, and velopharyngeal incompetence (VPI) marked by hypernasal speech and nasopharyngeal reflux of liquids during swallowing. METHODS: Palatal adhesion (PA), a procedure whereby the unilaterally paralyzed palate is attached to the posterior pharyngeal wall, decreases the size of the velopharyngeal port and minimizes the symptoms. This study assessed the outcome of PA in 31 patients with VPI secondary to proximal vagus nerve injury. RESULTS: PA decreased postoperative nasality in 96% of patients. Nasopharyngeal reflux was significantly improved in 83%. Three patients (11%) had minor wound breakdown postoperatively, all of which healed completely with conservative management. CONCLUSION: PA offers a favorable result with minimal concomitant morbidity and is recommended for patients with VPI secondary to unilateral proximal vagus nerve paralysis.

Adult↗
PubMed2002

Voice outcome following thyroplasty in patients with longstanding vocal fold immobility.

OBJECTIVE: Length of time elapsed between recurrent laryngeal nerve (RLN) injury and surgery may affect voice result. The purpose of this study was to compare voice outcome after thyroplasty in patients with short- and long-term vocal fold immobility. METHODS: Thirty-five patients with longstanding vocal fold immobility (8.3 years) and 35 patients more acutely denervated (10 months) underwent type I thyroplasty. Trained listeners before and after surgery rated perceptual judgments of voice. Acoustic and aerodynamic data were analyzed. RESULTS: Voice outcome did not differentiate the two groups with respect to objective measures. Perceptual ratings of post-operative voice quality favored the short-term patients, with the long-term group having a mildly 'constricted' quality. CONCLUSION: Thyroplasty yields a functional voice result even when substantial time has elapsed. Patients with chronic immobility may be unable to release longstanding hyperfunctional voicing behaviors even after surgery has afforded them an improved mechanism. In five of 35 long-term patients, therapy enhanced voice quality.

Acute Disease↗