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Biomedical subjects

Brian B Burkey

Publications and source records attributed to Brian B Burkey.

17 recordsLinked to original sources

Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas.

PURPOSE: High epidermal growth factor receptor (EGFR) gene copy number is associated with poor prognosis in lung cancer, but such findings have not been reported for HNSCC. A better understanding of the EGFR pathway may improve the use of EGFR inhibitors in HNSCC. PATIENTS AND METHODS: EGFR status was analyzed in 86 tumor samples from 82 HNSCC patients by fluorescent in situ hybridization (FISH) to determine EGFR gene copy number, by polymerase chain reaction and direct sequencing for activating mutations, and by DNA microarray and immunohistochemistry for RNA and protein expression. The results were associated with patient characteristics and clinical end points. RESULTS: Forty-three (58%) of 75 samples with FISH results demonstrated EGFR high polysomy and/or gene amplification (FISH positive). The FISH-positive group did not differ from the FISH-negative group with respect to age, sex, race, tumor grade, subsites and stage, or EGFR expression by analyses of RNA or protein. No activating EGFR mutations were found. However, the FISH-positive group was associated with worse progression-free and overall survival (P < .05 and P < .01, respectively; log-rank test). When microarray data were interrogated using the FISH results as a supervising parameter, ECop (which is known to coamplify with EGFR and regulate nuclear factor-kappa B transcriptional activity) had higher expression in FISH-positive tumors. CONCLUSION: High EGFR gene copy number by FISH is frequent in HNSCC and is a poor prognostic indicator. Additional investigation is indicated to determine the biologic significance and implications for EGFR inhibitor therapies in HNSCC.

Aneuploidy↗

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↗

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↗

Squamous cell carcinoma of the oropharynx and hypopharynx.

Oropharyngeal and hypopharyngeal squamous cell carcinomas require an interdisciplinary approach to manage patients appropriately. Tumor stage and histology, functional outcome, and patient comorbidities are important factors to consider. Various surgical approaches as well as chemotherapy and radiation therapy alone or in combination remain the mainstay of therapy.

Antineoplastic Agents↗

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↗

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↗

Functional outcomes after free flap reconstruction of the upper aerodigestive tract.

PURPOSE OF REVIEW: When the complex structures of the upper aerodigestive tract are disrupted after resection of head and neck tumors, an appropriate reconstructive option should be chosen in an attempt to regain maximum function. Reconstructions using microvascular free tissue transfer offer unparalleled flexibility, both in tissue composition and in placement. This article will examine functional outcomes after free flap reconstruction of the upper aerodigestive tract. RECENT FINDINGS: With the maturation of free tissue transfer techniques, functional outcomes are being analyzed with increasing frequency. Recent reports show promising results for free flap reconstruction of oral cavity, oropharyngeal, and hypopharyngeal soft tissue defects, as well as for bony mandibular and maxillary defects. SUMMARY: For both soft tissue and bony defects of the upper aerodigestive tract, microvascular free flaps provide good functional outcomes. In the future, randomized studies are needed to compare the functional outcomes of microvascular free flaps with those of other reconstructive options.

Esophagus↗

Current concepts in lip reconstruction.

PURPOSE OF REVIEW: Approximately 25% of all oral cavity carcinomas involve the lips, and the primary management of these lesions is complete surgical resection. The management of the resulting lip defect remains a significant reconstructive challenge, requiring meticulous preoperative planning and surgical technique to optimize the functional and cosmetic outcome. Reviewed here are the accepted techniques of lip reconstruction, as well newer techniques that have been reported. RECENT FINDINGS: There have been no major advances in lip reconstruction; rather, continued improvement on accepted techniques. The main goals of reconstruction remain the restoration of oral competence, maintenance of oral opening, and the restoration of normal anatomic relations such that both the active (smile) and passive (form) cosmetic outcome is acceptable. The reconstruction should be tailored to the individual needs of the patient and should take into account the patient's condition, local tissue characteristics, previous treatment(s), and functional needs (eg, denture use), in addition to the size and location of the defect. SUMMARY: The lips play a key role in facial expression, speech, and eating. This requires meticulous attention to preoperative planning and surgical technique to maximize the functional and cosmetic outcome. It is important to assess local tissue characteristics (skin laxity) and previous treatment (surgery and/or irradiation) before the surgical plan is made final. Local tissue should be used whenever possible to provide the least donor site morbidity and the best overall tissue color and texture match. Whenever possible, dynamic reconstruction should be attempted. Careful preoperative assessment and planning will allow the surgeon to reach an acceptable balance between form and function with the reconstruction.

Carcinoma↗

Use of the anterolateral thigh flap for reconstruction of the head and neck.

PURPOSE OF REVIEW: The anterolateral thigh free flap has achieved recent popularity in North America for the reconstruction of head and neck defects after ablative surgery. The flap is most often based on either the septocutaneous or musculocutaneous perforators of the descending branch of the lateral circumflex femoral artery. Its versatility allows for a subcutaneous, fasciocutaneous, myocutaneous, or adipofascial flap to be obtained. RECENT FINDINGS: Recent publications have described the utility of the anterolateral thigh flap for reconstruction of head and neck defects. It has been used successfully in the reconstruction of the laryngopharynx, oral cavity, oropharynx, external skin, and maxilla. Furthermore, when a thinner flap is needed, a suprafascial anterolateral thigh flap may be raised or the flap may be thinned after it is obtained. SUMMARY: The anterolateral thigh flap is a highly versatile and reliable flap for use in the reconstruction of various soft tissue defects of the head and neck. This flap has gained great popularity in mainland China, Taiwan, and Japan given its versatility, ability for a two-team approach, and minimal donor site morbidity. However, it has not met the same enthusiasm in Europe and North America because of the relative difficulty in perforator dissection, reported variations of the vascular anatomy, and the presumed increased thickness of the anterolateral thigh tissue in the Western population in comparison with the patient population of the Far East. These obstacles may be overcome by increased surgical experience and by the ability to create a thinner suprafascial flap or thinning the flap after it has been obtained.

Head↗

Lateral approach to a neurenteric cyst of the cervical spine: case presentation and review of surgical technique.

STUDY DESIGN: The lateral cervical spinal approach is illustrated by a case of neurenteric cyst. OBJECTIVES: To present a case of a neurenteric cyst resected the lateral cervical approach, and to review the approach in detail. SUMMARY OF BACKGROUND DATA: Intradural lesions located anterior to the high cervical spinal cord may present a difficult surgical problem. Neurenteric cysts are unusual lesions found in the brain and spinal cord. This report presents a case of cervical neurenteric cyst causing anterior cord compression that was resected using the lateral cervical approach. METHODS: A 32-year-old woman presented with chronic headaches and worsening nausea, tinnitus, dizziness, and hyperreflexia and clonus in her lower extremities. Magnetic resonance imaging of the cervical spine showed a mass compressing the anterior spinal cord at C3. Pathology showed that this lesion was a neurenteric cyst. The lesion was resected using the lateral cervical approach. RESULTS: At this writing, 36 months after surgery, the patient has continued resolution of her symptoms, and no cyst recurrence has been shown on repeat MRI imaging. She has no evidence of postlaminectomy kyphosis. CONCLUSIONS: The lateral cervical approach is useful for surgeons attempting to resect lateral and anterior intradural lesions of the cervical spine. It also gives excellent cranial-to-caudal access to the thecal sac, spinal cord, and the lesion to be resected. The neck incision preserves cosmesis, and neuromuscular function is maintained. Spinal fusion was avoided in the reported case.

Adult↗

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↗

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↗

Expression of p63 and 14-3-3sigma in normal and hyperdifferentiated mucosa of the upper aerodigestive tract.

OBJECTIVE: Our goal was to analyze p63 and 14-3-3sigma expression in normal and hyperdifferentiated head and neck mucosa. STUDY DESIGN: Compare the in vivo expression of p63 and 14-3-3sigma by immunohistochemistry in normal mucosa and oral lichen planus, a benign mucosal lesion marked by hyperdifferentiation and apoptosis. RESULTS AND CONCLUSION: p63 is underexpressed and 14-3-3sigma is overexpressed in lichen planus on immunohistochemical analysis. SIGNIFICANCE: The findings support the hypothesis that p63 plays an antidifferentiation role, whereas 14-3-3sigma plays a prodifferentiation role in the upper aerodigestive tract epithelium. Lichen planus is a valuable model for the study of p63, 14-3-3sigma, and mucosal differentiation. p63 and 14-3-3sigma may be molecular markers for oral lichen planus.

14-3-3 Proteins↗

Microvascular free tissue transfer in reconstructing skull base defects: lessons learned.

OBJECTIVE: To demonstrate the effectiveness of microvascular free tissue transfer in reconstructing complex skull base defects. STUDY DESIGN: Retrospective chart review. METHODS: A retrospective chart review was conducted identifying patients with anterior or lateral skull base defects, or both, who underwent microvascular free flap reconstruction. Appropriate demographic, pathological, and preoperative and postoperative clinical data were collected and analyzed. RESULTS: Thirty-five patients with skull base defects were identified, including 8 women (Mean age, 43.9 y; age range, 28-75 y) and 27 men (mean age, 57.9 y; age range, 19-85 y). Defects were secondary to trauma in two cases, whereas the remaining 33 cases were secondary to ablative procedures for a variety of malignant tumors, of which squamous cell carcinoma was the most common (n = 18). The average defect surface area was 89.3 cm(2), and 36 free flaps were used. The most commonly used flap was the rectus myocutaneous (n = 20); however, six different flap types were employed, including three radial forearm fascial flaps. In all, there were seven flap-related complications and there was one total flap loss. A total of 43 postoperative complications occurred in 23 patients, with the most common complications being grouped as intracranial (n = 10), orbital (n = 9), and cardiac (n = 9). The perioperative mortality rate was 5.7%, and the average hospital stay was 13.5 days (range, 7-37 d). CONCLUSIONS: The use of microvascular free tissue transfer for reconstruction of complex skull base defects has proven highly successful in the large series presented in the current study. The versatility and reliability of free flaps for such reconstruction are discussed, and helpful hints are given to minimize the complication rate.

Adult↗

Incidental metastatic papillary thyroid carcinoma in microvascular reconstruction.

OBJECTIVES/HYPOTHESIS: Occult papillary thyroid carcinoma has a reported prevalence of 1% to 35% based on autopsy studies. Cervical lymphatic metastases from papillary thyroid carcinoma have been associated with a higher likelihood of recurrence with a questionable impact on survival. Without clinically evident disease in the thyroid or cervical nodes, management of these patients presents a treatment dilemma. We propose an individualized treatment plan for patients in whom metastatic papillary thyroid carcinoma is incidentally detected during neck exploration for other purposes. STUDY DESIGN: Retrospective review and discussion of the literature. METHODS: The clinical course of two patients with incidentally discovered metastatic papillary thyroid carcinoma to the cervical lymph nodes is described. Both patients had previously received head and neck irradiation in childhood and required free flap reconstruction of extensive skull base defects following extirpation of meningiomas. RESULTS: Neck dissection specimens from levels I and II obtained during exposure of recipient vessels for microvascular tissue transfer revealed papillary thyroid carcinoma in both cases. The patients subsequently underwent total thyroidectomy, neck dissection, and postoperative radioactive iodine ablation of residual thyroid tissue. After 1 year of follow-up, both patients were without evidence of recurrent disease. CONCLUSIONS: An individualized approach is justified to treat metastatic papillary thyroid carcinoma incidentally discovered during other procedures. The case reports underscore the importance of pathological analysis of surgical specimens obtained during head and neck reconstruction.

Adult↗

The role of free tissue transfer in the reconstruction of massive neglected skin cancers of the head and neck.

BACKGROUND: Most skin cancers involving the head and neck region are easily managed with surgical resection and local flap rotation. Occasional patients present with massive neglected skin cancers or skin cancers that have recurred after multiple treatments. Management of these massive tumors may involve craniofacial resection, maxillectomy, or mandibulectomy to obtain clear margins. Reconstruction requires massive composite soft tissue replacement. We presented our experience with, to our knowledge, the largest series reported to date. DESIGN: A retrospective chart review of 43 patients with massive neglected skin cancer of the head and neck reconstructed by means of free tissue transfer from January 1, 1992, through October 1, 2001. SETTING: Academic tertiary referral medical center. RESULTS: Seventeen patients with squamous cell carcinoma and 26 patients with basal cell carcinoma were treated. Primary sites included the cheek (n = 15), ear (n = 8), forehead (n = 5), neck (n = 4), scalp (n = 5), and nose (n = 6). Treatment involved a combination of orbital exenteration (n = 16), maxillectomy (n = 12), mandibulectomy (n = 6), auriculectomy (n = 5), craniofacial resection (n = 10), rhinectomy (n = 6), and lateral temporal bone excision (n = 5). Flaps used for reconstruction included the rectus abdominis (n = 22), latissimus dorsi (n = 11), radial forearm (n = 8), and lateral arm (n = 2). Radiotherapeutic exposure included pretreatment in 21 patients and posttreatment in 15. Twelve patients had undergone no previous surgeries; 15 patients, 1 to 5; and 16 patients, more than 5. Follow-up revealed evidence of local recurrence (n = 12), locoregional recurrence (n = 3), distant metastasis (n = 3), and no evidence of disease (n = 25). CONCLUSIONS: Massive skin cancers are generally associated with disfiguring, debilitating surgery and high mortality rates. We demonstrate that free tissue transfer yields acceptable survival with functional and cosmetic outcomes.

Aged↗