bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ARF‐p16 Gene Locus in Carcinogenesis and Therapy of Head and Neck Squamous Cell Carcinoma
Authors: Yarbrough Wendell G. 
Published: November 2003

AbstractObjectives/Hypothesis We have identified families with a high incidence of tumors including head and neck squamous cell carcinoma (HNSCC). The occurrence of melanoma in these kindreds suggested that the ARF‐p16 gene may be involved in carcinogenesis. We wished to determine the gene defect associated with the familial predisposition to HNSCC and to determine whether restoration of the gene may have therapeutic benefit.Study Design Translational molecular research.Methods Molecular techniques were used to identify mutations of the ARF‐p16 gene from the affected families and to test the activity of p16 and ARF mutants. In additional, HNSCC tumor tissue was analyzed to determine whether the wild‐type p16 allele was lost or maintained. ARF‐expressing adenoviruses were created, and their effect on HNSCC cell lines and normal head and neck epithelial cells was determined.Results Mutation of the ARF‐p16 gene was found in two families with predisposition to develop HNSCC. Independent mutations detected in the germline DNA of both families inactivated p16, but not ARF, and the inactive mutant p16 allele segregated with disease within both families. The wild‐type p16 allele was lost in HNSCC tumor tissue from both families. The efficacy of ARF in treatment of HNSCC was found to depend on retention of p53 activity within HNSCC tumor cells. Remarkably, ARF expression was found to kill cells, depending on loss of retinoblastoma activity. Because loss of retinoblastoma activity is nearly universal in tumors, ARF killed tumor cells that retained p53, but ARF spared normal cells.Conclusions Our results support the recognition of a new clinical entity of familial head and neck cancer. We have shown that this syndrome is associated with inactivating mutations of the p16 gene that these mutations segregate with disease in two described families. Loss of the wild‐type p16 allele in HNSCC tissue from both families strongly supports the role of the mutant p16 in carcinogenesis. We have also investigated the therapeutic utility of the alternate reading frame product of the p16 gene, ARF. The finding that ARF kills cells depending on loss of retinoblastoma activity and retention of p53 suggests that ARF may be effective in treatment of roughly 50% of head and neck cancers while sparing normal cells. Recognition of p16 mutations as an etiological factor in familial HNSCC provides an accessible tool for diagnosis of this syndrome. Clinical acceptance of familial head and neck cancer will ensure that patients are appropriately diagnosed and managed.
The Ulnar Fasciocutaneous Free Flap in Head and Neck Reconstruction
Authors: Wax Mark K. , Rosenthal Eben L. , Winslow Catherine P. , Bascom Daphne A. , Andersen Peter E. 
Published: November 2003

AbstractObjectives/Hypothesis The radial forearm fasciocutaneous free flap has become the reconstructive tissue of choice for the majority of soft tissue defects in the head and neck. The forearm skin has many of the ideal soft tissue characteristics that optimize reconstruction and rehabilitation in these patients. The tissue is malleable, supple, and moldable in three dimensions; has a reliable pedicle; and can be harvested with a two‐team approach. In some patients, the radial forearm cannot be used. An alternative is to use the adjacent tissue, which shares identical tissue characteristics. This tissue gets its vascular supply from the ulnar artery. The purpose of the report was to describe the authors' experience with the ulnar fasciocutaneous free flap in head and neck reconstruction.Study Design Prospective consecutive case series.Methods Retrospective review of all patients undergoing ulnar fasciocutaneous free tissue transfer by a group of microvascular surgeons was performed. Thirty patients underwent free tissue transfer using the ulnar fasciocutaneous free flap. The male‐to‐female ratio was 3:1.Results Defects were located in the oral cavity (14), oropharynx (12), neck skin (1), and soft tissue of the lateral skull (3). The average size of the skin paddle that was transferred was 7 × 10 cm (range, 3 × 5 to 9 × 12 cm). The mean area of tissue that was transferred was 70 cm2 (range, 15–108 cm2). Vessel sizes were somewhat smaller than the comparable radial forearm. One patient had complete loss of the skin graft on the donor site. There were no median nerve or other wound‐healing problems. Two flaps were lost in the postoperative period. Indications for use of the ulnar fasciocutaneous free flap were failed Allen's test (23), use of a less hairy part of the forearm (3), and surgical preference (4).Conclusions The ulnar fasciocutaneous free flap has all of the tissue characteristics of the radial forearm flap. When a radial forearm flap cannot be used and forearm skin is desired, consideration of an ulnar fasciocutaneous free flap should be undertaken.
Incidental Metastatic Papillary Thyroid Carcinoma in Microvascular Reconstruction
Authors: Moore Brian A. , Duncan Irenee M. , Burkey Brian B. , Day Terry 
Published: November 2003

AbstractObjectives/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.
Computed Tomography's Ability to Predict Sacrifice of Hypoglossal Nerve at Resection
Authors: Dubin Marc G. , Ebert Carlos S. , Mukherji Suresh K. , Pollock Hoke W. , Amjadi Darius , Shockley William W. 
Published: November 2003

AbstractObjective To assess whether preoperative computed tomography (CT) scan can determine if the hypoglossal nerve (cranial nerve XII) will be sacrificed in floor‐of‐mouth, oral tongue, and tongue base tumor resections.Study Design Retrospective review.Methods Patients who underwent resection of floor‐of‐mouth, oral tongue, and tongue base tumors from 1990 to 1999 were identified. Preoperative CT scans were reviewed by a neuroradiologist. The postoperative status of cranial nerve XII was predicted to be “saved” or “sacrificed.” Hypoglossal nerve “sacrifice” was predicted if the fat planes surrounding the takeoff of the proximal lingual artery were obliterated by tumor. The nerve was determined to be sacrificed or spared during resection by review of the operative report.Results Of the 45 patients, 14 tumors were predicted radiographically to involve the hypoglossal nerve. Twenty‐seven of 31 nerves that were predicted to be saved were saved at the time of surgery. Seven of 14 nerves that were predicted to be sacrificed were sacrificed at the time of surgery. The sensitivity was 0.64 (95% confidence interval [CI], 0.35–0.86) with a specificity of 0.79 (95% CI, 0.70–0.87). The positive predictive value was 0.50 (95% CI, 0.27–0.68) with a negative predictive value of 0.87 (95% CI, 0.77–0.95).Conclusions The ability to predict preoperatively whether a tumor can be resected without sacrificing the hypoglossal nerve would be an important factor in determining management of these tumors. The results indicate that CT scan accurately predicts the ability of the surgeon to spare the hypoglossal nerve (negative predictive value, 87%) with a specificity of 0.79.
Human Septal Chondrocyte Redifferentiation in Alginate, Polyglycolic Acid Scaffold, and Monolayer Culture
Authors: Homicz Mark R. , Chia Stanley H. , Schumacher Barbara L. , Masuda Koichi , Thonar Eugene J. , Sah Robert L. , Watson Deborah 
Published: November 2003

AbstractObjectives/Hypothesis Tissue engineering laboratories are attempting to create neocartilage that could serve as an implant material for structural support during reconstructive surgery. One approach to forming such tissue is to proliferate chondrocytes in monolayer culture and then seed the expanded cell population onto biodegradable scaffolds. However, chondrocytes are known to dedifferentiate after this type of monolayer growth and, as a result, decrease their production of cartilaginous extracellular matrix components such as sulfated glycosaminoglycans. The resultant tissue lacks the biomechanical properties characteristic of cartilage. The objective of the study was to determine whether different culture systems could induce monolayer‐expanded human septal chondrocytes to redifferentiate and form extracellular matrix.Study Design Laboratory research.Methods Chondrocytes were isolated from human nasal septal cartilage of five donor patients (age, 35.8 ± 9.3 y). Cell populations were seeded at low density (30,000 cells/cm2) into monolayer culture and expanded for 4 to 6 days. Following trypsin release, chondrocytes were placed into three different systems for neocartilage formation: alginate beads, polyglycolic acid scaffolds, and monolayer. After 7 and 14 days of growth, neocartilage was analyzed using histological and quantitative biochemical assessment of cellularity (Hoechst 33258 assay) and sulfated glycosaminoglycan content (dimethyl methylene blue assay).Results Histologically, alginate beads contained spherical chondrocytes surrounded by dense extracellular matrix, an appearance similar to that of native cartilage. In contrast, polyglycolic acid scaffolds and monolayer cultures contained elongated cells with scant staining for matrix sulfated glycosaminoglycans, which are features that are characteristic of dedifferentiated chondrocytes. Biochemical analysis demonstrated a lower level of cell proliferation (P <.001) in scaffolds (+52% over baseline) and alginate (+96% over baseline) than in monolayer (+366% over baseline), as well as a higher content of sulfated glycosaminoglycans per cell (P <.001), after 14 days of growth in alginate culture than in either polyglycolic acid scaffolds (19‐fold difference) or monolayer (98‐fold difference).Conclusions Of the systems compared, monolayer‐expanded human septal chondrocytes demonstrated the greatest accumulation of sulfated glycosaminoglycans per cell when grown in alginate beads. Future research on cartilage tissue engineering may use alginate culture for reverting dedifferentiated cells back to the chondrocytic phenotype.
Cochlear Implantation in Patients With Auditory Neuropathy of Varied Etiologies
Authors: Mason John C. , De Michele Anne , Stevens Christopher , Ruth Roger A. , Hashisaki George T. 
Published: November 2003

AbstractObjectives/Hypothesis Auditory neuropathy is a relatively recently described pattern of hearing loss characterized by preservation of outer hair cell function despite absent brainstem auditory evoked responses. Intact outer hair cell function is demonstrated by the presence of otoacoustic emissions and/or a measurable cochlear microphonic on electrocochleography, whereas no synchronous neural activity (absent action potentials) is seen on acoustically evoked brainstem auditory evoked response testing. The study reviews the authors' experience with six patients diagnosed with auditory neuropathy, four of whom have undergone cochlear implantation.Materials and Methods A retrospective review of all medical and audiological charts at the University of Virginia Hospitals (Charlottesville, VA) was performed to identify patients who have undergone cochlear implantation or have been diagnosed with auditory neuropathy, or both.Results Six patients with hearing loss attributable to auditory neuropathy were identified, four of whom have undergone cochlear implantation. Causes varied, including congenital, infectious, and idiopathic origins. Adults demonstrated subjective auditory perception on promontory stimulation, whereas no repeatable brainstem auditory evoked response waveforms could be demonstrated on pediatric promontory stimulation testing. Patients with implants demonstrated implant‐evoked brainstem auditory evoked responses and improved audiological performance.Conclusions The six cases presented in the study represent varied causes and, probably, varied sites of lesions of auditory neuropathy. Promontory stimulation has been valuable, particularly in adults. Cochlear implantation allows the opportunity to provide a supraphysiological electrical stimulation to the auditory nerve, with the hope of reintroducing synchronous neural activity. Greater confidence and enthusiasm for cochlear implantation in appropriately selected patients with auditory neuropathy are gained through experience with such diverse cases.
Esthesioneuroblastoma: The Northwestern University Experience
Authors: Argiris Athanassios , Dutra Jose , Tseke Paraskevi , Haines Kenneth 
Published: November 2003

AbstractObjective To review our experience with esthesioneuroblastoma, a rare malignancy of the head and neck.Study Design Retrospective review of Tumor Registry data.Methods We performed a computerized search of the Northwestern Memorial Hospital Tumor Registry database from 1981 to 2000.Results Sixteen patients with esthesioneuroblastoma were identified and analyzed. Their mean age was 42 years. Eleven of 16 patients (69%) had Kadish stage C; 8 patients (50%) had brain involvement at presentation. Craniofacial resection was performed in 13 patients (81%). Fourteen patients received either preoperative or postoperative therapy; radiation therapy was employed in 11 cases and chemotherapy in 4. The actuarial 5‐year survival was 60%, and the actuarial 5‐year disease‐free survival was 33%, with a median follow‐up of 4.3 years. Recurrences occurred at a median time of 11 months after diagnosis (2.5 mo–18 y). The first site of failure was locoregional alone in 10 of 12 patients who progressed, and in 6 patients involved the brain or the meninges. Two patients were successfully salvaged. Patients with high‐grade tumors had a trend toward work survival.Conclusions Esthesioneuroblastoma is a rare tumor that is potentially curable by surgical resection and radiation therapy. However, the rate of local failure is high, and late recurrences are not uncommon. The role of chemotherapy warrants further investigation.
Association Between Tobacco Use and Metastatic Neck Disease
Authors: Mansour Ossama I. , Snyderman Carl H. , D'Amico Frank 
Published: November 2003

AbstractObjectives/Hypothesis Tobacco has multiple effects on connective tissues that might affect tumor behavior. This study examined the association between tobacco use and tumor behavior (lymphatic metastasis and extracapsular spread) in head and neck cancers.Study Design Chart audit.Methods Medical records of patients from the Department of Otolaryngology, University of Pittsburgh Medical Center (Pittsburgh, PA) with oral cavity, pharyngeal, and laryngeal cancers who underwent neck dissection were reviewed focusing on their tobacco use habits, as well as the clinical and pathological criteria of primary tumors and cervical lymph nodes. Univariate and multivariate analyses were performed to study the significance between pathological and tobacco use variables.Results The study included 171 patients. Both univariate and multivariate analyses revealed significant associations between tobacco use and pathological findings. Cervical metastasis was observed in 100% of tobacco users and 54% of nonusers (P <.0001). Extracapsular spread was observed in 100% of tobacco users and 19% of nonusers (P <.0001). Tobacco use was independently associated with pathological nodal stage in multivariate analysis. Former users and light users of tobacco were not at reduced risk of cervical metastasis or extracapsular spread.Conclusions The study demonstrates that tobacco use is a possible risk factor for cervical metastasis and extracapsular spread, which may be helpful information in planning therapy for patients with clinically staged node‐negative necks.
The Long‐Term Evaluation of Tracheostomy in the Management of Severe Obstructive Sleep Apnea
Authors: Thatcher Gentry W. , Maisel Robert H. 
Published: November 2003

AbstractObjective To determine the long‐term success and morbidity of tracheostomies for patients with severe obstructive sleep apnea.Study Design A retrospective study of patients who have undergone tracheostomy for documented obstructive sleep apnea at Hennepin County Medical Center since 1979.Methods Retrospective chart review of all tracheostomy patients operated January 1, 1979, to June 30, 1999, were evaluated. Follow‐up data from patient records, death certificates, and DMV.Results Seventy‐nine patients (70 men and 9 women; age range, 25–70 y; mean age, 47 y) received tracheostomies at a regional sleep disorder center. Respiratory distress index ranged from 45 to 146 (mean value, 81). Tracheostomy eliminated obstructive sleep apnea in all cases. Follow‐up ranged from 3 months to 20 years (mean period, 8.3 y). In all, 16 patients had decannulation (range, 2 mo to 13 y): 5 of the patients chose continuous positive airway pressure, 3 grew intolerant of their tracheostomy, 3 had obstructive sleep apnea fully resolve after uvulopalatopharyngoplasty, 3 unknown diagnosis for decannulation, 2 had significant weight loss. Morbidity seen within the first year was primarily limited to granulation tissue, infection, and stoma revision. Fourteen deaths were identified. Average age at time of death was 62 years. Five deaths were cardiopulmonary related, four were from cancer, two were from postoperative complications of unrelated surgery, and one was from aspiration. Tracheostomy‐related mortality included one postoperative myocardial infarction and one tracheal‐innominate fistula.Conclusion Severe obstructive sleep apnea and its comorbid conditions are effectively treated in the long term with tracheostomy. Initial management of more frequent complication is well tolerated. Significant morbidity and mortality are low. Chances of obstructive sleep apnea resolution allowing decannulation remain poor.
Bordetella pertussis Causing Otitis Media: A Case Report
Authors: Decherd Michael E. , Deskin Ronald W. , Rowen Judith L. , Brindley Mace B. 
Published: November 2003

AbstractObjective/Hypothesis Bordetella pertussis is an unusual cause of otitis media with effusion. We report a case in a neonate.Study Design Case report.Methods A case is presented.Results A 1‐month‐old infant girl was admitted because of respiratory distress and subsequently was found to have pertussis. On examination she was noted to have a middle ear effusion. Myringotomy was performed for culture. Culture confirmed B pertussis. We were unable to find a previous report of B pertussis otitis media.Conclusion Bordetella pertussis has been identified in the middle ear effusion of an infant with the pertussis syndrome.
Healing of Composite Chondrocutaneous Auricular Grafts Covered by Skin Flaps in Nasal Reconstructive Surgery
Authors: Keck Tilman , Lindemann Jörg , Kühnemann Stephan , Sigg Otto 
Published: November 2003

AbstractObjective/Hypothesis Healing of composite chondrocutaneous auricular grafts combined with overlying skin flaps for reconstruction of the internal lining in partial nasal defects should be evaluated.Study Design A retrospective chart review and prospective clinical follow‐up of 15 patients with partial nasal defects.Methods Fifteen patients with partial defects of the middle and lower third of the nose were reviewed. Nineteen composite ear grafts were used for reconstruction of the internal nasal lining in the patient group. The composite grafts were used in combination with overlying nasolabial transposition flaps. In some patients paramedian forehead or turn‐in flaps were needed as well. Functional and aesthetic results of nasal reconstruction were subjectively graded by the patients and medical doctors of the department.Results Three of 19 transplanted composite grafts showed postoperative deformation. Relative shrinkage was observed in 5 of 19 composite grafts, whereas complete loss of the composite graft was seen in only one patient. Nasal airway obstruction was observed in the patients with deformity or loss of composite graft (4 of 15 patients), and an unsuccessful aesthetic result was seen only in the patient with total composite graft failure (1 of 19 transplanted grafts).Conclusions Composite ear grafts may provide good functional and aesthetic results when combined with overlying skin flaps in reconstruction of partial nasal defects. Even though composite ear grafts used for restoration of the inner nasal lining may be deformed or absorbed and impairment of nasal airway patency or aesthetic result may be postoperatively observed, the combination of composite ear grafts with locoregional transposition flaps provides additional reconstructive options for selected nasal defects.