Design of multifunctional nanomedical systems.

Multifunctional nanoparticles hold great promise for drug/gene delivery and simultaneous diagnostics and therapeutics ("theragnostics") including use of core materials that provide in vivo imaging and opportunities for externally modulated therapeutic interventions. Multilayered nanoparticles can act as nanomedical systems with on-board molecular programming done through the chemistry of highly specialized layers to accomplish complex and potentially decision-making tasks. The targeting process itself is a multi-step process consisting of initial cell recognition through cell surface receptors, cell entry through the membrane in a manner to prevent undesired alterations of the nanomedical system, re-targeting to the appropriate sub-region of the cell where the therapeutic package can be localized, and potentially control of that therapeutic process through feedback systems using molecular biosensors. This paper describes a bionanoengineering design process in which sophisticated nanomedical platform systems can be designed for diagnosis and treatment of disease. The feasibility of most of these subsystems has been demonstrated, but the full integration of these interacting sub-components remains a challenge for the field. Specific examples of sub-components developed for specific applications are described.

Closed tympanomastoidectomy.

The role of closed tympanomastoidectomy in the treatment of chronic ear disease continues to be a subject of debate. This article reviews the position of closed tympanomastoidectomy in the armamentarium of the otolaryngologist. In this article the technique is described and indications are reviewed. A brief history of closed tympanomastoidectomy and the issue of outcome from surgery are also addressed.

Clinical applications of frameless stereotactic devices in neurotology: preliminary report.

Conventional stereotactic surgery has been utilized primarily for intracranial neuro-surgical procedures. Despite their utility, head-frame systems are restrictive and often inconvenient, thus they have not proved applicable for neurotologic surgery. Recently frameless stereotactic navigational systems have been developed that employ three-dimensional digitizers to transform the coordinates in surgical space to the corresponding image space, without the employment of head frames. This allows the determination of position of a surgical instrument in real time during surgery, and its display on video-projected computed tomography or magnetic resonance imaging scanned images. This preliminary report focuses upon an optoelectric referenced frameless stereo-tactic system, the NeuroStation, as it relates to minimally invasive neurotologic surgery. Clinical applications, limitations, and future directions are discussed, and three representative surgical cases are presented. This device has potential as an adjunctive navigational tool for certain neurotologic procedures.

Labyrinthectomy. Indications and surgical technique.

Surgical intervention is considered for patients whose disabling vertigo fails to respond to appropriate medical therapy. Topics discussed in this article include indications, preoperative assessment, and surgical techniques. Fifteen case studies supplement the text, followed by a discussion.

The importance of the eosinophil in head and neck cancer.

In a previous study, we found tumor-associated tissue eosinophilia (TATE) to be a favorable prognostic indicator for squamous cell carcinoma of the head and neck (p less than 0.05). The present expanded study was undertaken to confirm this finding. The pathology of 120 head and neck tumors was examined for histologic features suggestive of poor prognosis. Ten descriptive histopathologic variables, including two malignancy grading scales, were correlated with DNA flow cytometric data and clinical outcome. No correlation was found between the malignancy grading scales and DNA flow cytometric data or clinical outcome. The present expanded study confirmed with greater statistical significance (p less than 0.001) that high-grade TATE is a favorable prognostic indicator for head and neck cancer. Furthermore, high-grade TATE was associated with the absence of distant metastasis (p less than 0.05). Using a stepwise logistic regression analysis of the clinicopathologic variables in the study, high-grade TATE was the most influential variable affecting clinical outcome, followed by border, stage, and perineural invasion. We conclude that the grade of TATE is a significant prognostic indicator for head and neck cancer. The significance and possible role of the eosinophil in the tumor-host interaction are discussed.

Iodine-125 seed implantation as an adjunct to surgery in advanced recurrent squamous cell cancer of the head and neck.

Survival for extensive recurrent squamous cell carcinomas of the head and neck remains poor, with the major cause of death being local recurrence. Surgical implantation of iodine-125 interstitial seeds allows tumoricidal doses of radiation to be delivered to residual tumor while minimizing radiation doses to the surrounding tissues. From 1978 to 1988, 39 implantations were performed on 35 patients for extensive recurrent squamous cell carcinoma of the head and neck. The decision for implantation was based on positive margins or close to resection margins from frozen sections after salvage resection. The determinate 5-year disease-free survival was 41%, with both the overall and no evidence of disease 5-year survivals being 29%. Significant complications occurred in 36% of all cases. This figure increased to 56% when flap reconstruction was required. Possible reasons for this seemingly high complication rate are discussed. Considering the advanced nature of these recurrent carcinomas, surgical resection with iodine-125 seed implantation appears to be an effective method of managing disease that might otherwise be judged unresectable and treated for palliation only.

Endoscopic sinus surgery for mucoceles: a viable alternative.

Functional endoscopic surgery affords the potential for dramatically reducing operative morbidity of surgery for paranasal sinus mucoceles by offering a minimally invasive approach under local anesthesia. Following surgery, direct endoscopic visualization of the area enables accurate follow-up. Unlike sinus obliteration, the ability to accurately image the sinus by CT is also preserved. This paper presents our preliminary experience with 18 mucoceles in which endoscopic sinus surgery was attempted. Five patients had preoperative proptosis and diplopia, three had Pott's puffy tumor and five had erosion of the posterior table of the frontal sinus. Fifteen patients were satisfactorily treated endoscopically, two lesions could not be satisfactorily approached and required external surgery, and one patient had persistent disease. No disease recurrence has been noted to date with endoscopic follow-up of up to 42 months.

A prospective randomized study of four commonly used tympanostomy tubes.

Tympanostomy tube placement has clearly been shown to be an efficacious treatment for recurrent bouts of acute otitis media or chronic otitis media with effusion. However, there are few objective, prospective, randomized studies present in the literature to aid the clinical otolaryngologist with the proper tube choice for middle ear aeration. A prospective, randomized study was undertaken of four commonly used tympanostomy tubes. Shepard Teflon grommet, Armstrong beveled tube, Reuter-Bobbin tube, and Goode T-tube. This study was undertaken to determine which of these tubes had the fewest number of postplacement complications, including otorrhea, plugging, residual perforation, or chronic persistence in the tympanic membrane. Average follow-up was 17 months. The Shepard and Armstrong tubes showed a comparatively low rate of plugging and otorrhea. Both tubes had extrusion times that averaged less than 1 year. The Reuter-Bobbin tube had a much greater rate of plugging, compared to the other tubes. The T-tube had an increased incidence of otorrhea and persistence in the tympanic membrane well beyond 1 year. The T-tube was also the only tube in this study associated with residual perforations.

Current management of salivary gland tumors. Part 2.

The authors base their treatment of salivary gland malignancies on the size of the primary and the histopathologic diagnosis. Group 1 includes smaller tumors in the T1 and T2 classification with cell types that are associated with slow growth. A parotidectomy is usually sufficient therapy for tumors in this group. Group 2 contains T1 and 2 tumors with more aggressive behavior. Total parotidectomy is indicated here, with postoperative radiotherapy. T3 tumors and patients with nodal metastasis or recurrent tumors make up group 3. Radical parotidectomy with sacrifice of the facial nerve is usually required for a sufficient tumor-free margin in these patients, and postop radiotherapy is also necessary. Group 4 includes T4 lesions. Extent of disease dictates magnitude of excision and amount of postop radiotherapy.

Incidence, diagnosis, and classification of salivary gland tumors. Part 1.

The diagnosis of salivary gland tumors is complicated by their relative infrequency, the limited amount of pretreatment information usually available, and the wide range of biologic behaviors seen with different histopathologic types. Most salivary gland neoplasms originate in the parotid, 10-15% arise from the submandibular glands, and the rest occur in the sublingual and minor salivary glands. The probability of a salivary gland neoplasm being malignant is inversely proportional to the size of the gland. The authors discuss two major theories of histogenesis, itemize the various benign and malignant varieties of tumor, discuss the presentation and prognosis for each type, and present a list of factors that influence survival. They also discuss the newest staging system.

Compound pharyngeal myocutaneous flap.

Rehabilitation of major palatal ablative defects associated with lateral composite resection of the tonsil, base of tongue, and/or hemimandible is a difficult problem. Palatal reconstruction is described with emphasis on the compound medially based posterior pharyngeal, pectoralis major myocutaneous flap, which we have found to be an effective and reliable means of reconstructing these defects.

A method of closure after resection of anterior floor of mouth cancers.

A variety of methods may be used to reconstruct head and neck defects after ablative surgery for cancer. Increasingly, choices of reconstructive techniques must be made on the basis of functional results attained. Described is a method of reconstruction for anterior floor of mouth defects with marginal mandibulectomy, which has yielded good functional results. All patients undergoing this form of reconstruction are on a soft oral diet, without drooling and with good speech intelligibility.

Presentation and management of postcricoid hemangiomata in infancy.

Phillips and Ruh (1912) were the first to describe a congenital hemangioma of the larynx. Sweetser subsequently classified laryngeal hemangiomata into infantile and adult types and noted differences in incidence, location, and symptoms. According to Sweetser, the infantile form is less common, is almost always subglottic, and presents with stridor which may be intermittent. The adult form is somewhat more common, is generally supraglottic, and often presents with hoarseness or dysphagia. We present what we believe is the first reported case of a postcricoid hemangioma in an infant. A review of hemangiomata of the aerodigestive tract is presented and treatment is discussed.

DNA flow cytometry as a prognostic indicator in head and neck cancer.

The prognostic significance of deoxyribonucleic acid (DNA) flow cytometry has been investigated for many solid tumors, but few data have been accumulated for squamous cell carcinomas of the head and neck. To our knowledge, we report the largest number of patients (69) with head and neck primary carcinomas to be studied by DNA flow cytometry. In the first part of this study, we reviewed 109 consecutive patients with laryngeal or hypopharyngeal primary carcinomas which were treated at North Carolina Memorial Hospital during the period of 1981 to 1984. The final analysis comprised 139 DNA histograms (mean coefficient of variation: 8.02) on paraffin-embedded specimens from 48 patients. Of the 48 patients with primary carcinomas, 24 had glottic, 18 had supraglottic, and 6 had carcinomas from the piriform sinus. Patients had follow-up for a minimum of 12 months, with a mean follow-up period of 23 months. Twenty-three of the 48 primary carcinomas (48%) were clearly aneuploid, and the remaining 52% were tetraploid (22%) or diploid (30%). We have concluded that patients with clearly aneuploid primary carcinomas had significantly better prognoses than those with diploid tumors (p = 0.008). High DNA amounts (greater than 40% of cells beyond the diploid peak, DNA G1G0) also correlated with a favorable prognosis when compared with low DNA amounts (p less than 0.01), and this remained significant when the clinical outcome was adjusted for staging of the primary site (T), nodal status, and stage of disease. Ploidy was the most significant prognostic variable for the laryngeal group of patients. In the second part of the study, twenty-one patients with oral cavity squamous cell carcinomas were studied in a similar fashion as the group with laryngeal carcinomas. In this group, a low DNA amount, with 40% as the cutoff point, was associated with a favorable prognosis (p = 0.024), and this remained significant while controlling for T, nodal status, and stage of disease. Numbers were too small to permit evaluation of the impact of ploidy in this group, but there was a slight trend toward aneuploidy and tetraploidy, correlating with a poor treatment outcome (p = 0.228). DNA amount was the most significant prognostic variable for the group of patients with oral cavity carcinomas.(ABSTRACT TRUNCATED AT 400 WORDS)

The prognostic significance of stromal eosinophilia in head and neck cancer.

The pathologies of 82 head and neck tumors were examined for histologic features suggestive of poor prognoses. Twelve descriptive histopathologic variables, including two grading scales for malignant tumors, were correlated with DNA flow cytometric data and clinical outcome. We found no correlation between the grading scales and DNA flow cytometric data or clinical outcome. Only one of the histopathologic variables--stromal eosinophilia--was found to significantly correlate with favorable outcome (p = .018). Stromal eosinophilia may be an important new prognostic indicator for head and neck cancer.