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.     

Minimally invasive parathyroidectomy: the role of radio-guided surgery

OBJECTIVES: Objectives were to review our current experience with radio-guided parathyroid surgery and to compare various techniques of minimally invasive parathyroidectomy. STUDY DESIGN: 1) To review our recent experience of radio-guided gamma probe localization during surgery for primary hyperparathyroidism and 2) to compare the intraoperative findings with the preoperative sestamibi scan. METHODS: Analysis was made of the 10 most recent surgical procedures for primary hyperparathyroidism at a single institution to compare the operative localization with preoperative sestamibi scan and to determine the radioactivity in the tissue removed during surgery, such as parathyroid adenoma, normal parathyroid gland, thyroid tissue, or lymph nodes. RESULTS: The sestamibi scan was able to localize the enlarged parathyroid gland in eight patients. Although gamma probe was helpful in localizing the parathyroid gland, the identification of an enlarged parathyroid gland was directly based on the preoperative findings of sestamibi scan. In the remaining two patients, the intraoperative gamma probe was not helpful. CONCLUSIONS: The major advantage of gamma probe in the series was to evaluate the radioactivity in the tissue that was removed and to determine whether it was an enlarged parathyroid gland, lymph node, thyroid tissue, or fatty tissue. The radio-guided surgery did not add substantially to the surgical procedure in patients in whom the sestamibi scan had localized the enlarged parathyroid gland preoperatively.     

Management of sarcomas of the head and neck in adults

Sarcomas account for less than 1% of all malignant neoplasms occurring in the head and neck in adults. These tumors exhibit variable growth and degrees of aggressiveness which are primarily dependent on histologic grade. The pattern of growth demonstrated by sarcomas is generally by local advancement with high-grade tumor exhibiting extensive involvement of adjacent visceral and neurovascular structures. Regional metastasis is uncommon. Etiologic considerations include the tumorigenic effects of prior external beam radiotherapy and the development of second malignancies in the form of sarcomas. The clinical presentation of these neoplasms is variable and dependent on subsite of involvement as well as the aggressiveness of tumor growth. Histologic diagnosis is frequently challenging, often requiring the aid of immunohistochemical staining techniques. Treatment is predominantly surgical, utilizing wide local excision where en-bloc resection is feasible. Radiotherapy, by means of external beam or implant, plays an important adjunctive role in management, especially for tumors where en-bloc resection with margin control is not possible. Chemotherapy regimens are available for soft tissue neoplasms and osteosarcoma and are primarily designed to improve local control. Survival is predicted on the incidence of local recurrence and risk of distant metastasis, both of which are influenced by tumor grade. Low-grade tumors exhibit improved survival over that of less differentiated tumors.     

Current philosophy on the management of cancer of the base of the tongue

Cancer of the base of the tongue is a challenging disease for the head and neck surgeon, radiation oncologist and medical oncologist. However, over the last 10-15 years, improved treatment strategies have evolved which offer patients high probability of loco-regional control, survival, and good quality of life. The ability to offer patients good oncologic and functional outcomes serves as a paradigm for the successful application of multidisciplinary care, and the emphasis on quality of life in head and neck cancer treatment. This review provides an overview of the treatment options that exist, their advantages and disadvantages, and hopefully provides proper guidelines for the current management of this challenging disease.     

Sentinel lymph node biopsy in head and neck cancer

In the past decade, the technique of sentinel lymph node biopsy (SLNB) has been applied to a vast array of primary neoplasms, ranging from head and neck melanoma to vulvar carcinoma. At present, experience with SLNB is greatest in patients with melanoma and breast cancer. In view of the well known complications associated with cervical node dissection, it has been suspected for some time that cervical SLNB, if successful, might reduce the morbidity associated with the definitive care of patients with head and neck cancers. This report assesses the current status of SLNB in the treatment of head and neck cancers; while formal investigations of the efficacy of this technique are recommended, SLNB has not yet been demonstrated to possess the same level of utility seen in SLNB in melanoma and breast cancer patients. As a consequence, the application of SLNB to head and neck cancers remains an experimental technique--one which has not yet acquired the status of the standard of patient care.     

Duration of patency of laser-assisted tympanic membrane fenestration

BACKGROUND: Laser-assisted tympanic membrane fenestration (LTMF) provides intermediate-duration middle ear ventilation, which benefits selected children with acute otitis media (AOM) and otitis media with effusion (OME). OBJECTIVE: To evaluate clinical and technical factors that may affect duration of LTMF patency. DESIGN: Prospective clinical cohort effectiveness trial. SETTING: Four tertiary care children's hospitals. PATIENTS: Volunteer sample of 251 children (430 ears) followed up at 1, 2, 3, 4, 8, and 12 weeks; time to fenestration closure was evaluable in 201 ears, and assessment of cure at study conclusion was evaluable in 128 ears. INTERVENTIONS: Laser-assisted tympanic membrane fenestration for prospectively defined AOM or OME. The surgeon determined spot size, wattage, and concurrent adenoidectomy based on clinical judgment. MAIN OUTCOME MEASURES: Cure of AOM/OME with effusion at 90 days and duration of LTMF patency relative to spot size (1.8-2.8 mm), fenestration location on tympanic membrane, power (7-22 W), concurrent adenoidectomy, age, diagnosis (AOM vs OME), type of effusion, and preoperative tympanogram characteristics. Results are based on the number of ears that could be evaluated at each data collection interval. RESULTS: Fenestrations remained patent for 2 to 4 weeks (mean = 2.52, median = 2.0, SD = 1.4, n = 201); 97.4% were closed at 6-week follow-up. Spot sizes of 2.4 and 2.6 mm had a higher rate of patency than 2.0-mm spot size at 3 weeks following LTMF. Cure at 90 days was related to duration of patency for all patients combined and for patients treated for AOM and OME, but not for those undergoing adjunctive adenoidectomy. Cure at 90 days was related to larger spot size for all patients combined and those treated for AOM. Other investigated factors did not achieve statistical significance. CONCLUSIONS: Spot size of 2.4 mm or greater results in improved duration of LTMF patency, persisting for up to 3 weeks after LTMF, especially for treatment of AOM. Increased duration of LTMF patency correlates with greater incidence of cure of middle ear effusion at 90 days. Additional investigation is indicated to determine optimum spot size and optimum duration of patency for disease- severity-adjusted populations.     

Primary mucosal malignant melanoma of the head and neck

INTRODUCTION: The relative rarity of mucosal melanomas of the head and neck (MMHN) has made analysis of treatment approaches difficult. Advances in diagnostic techniques and treatment interventions have had obvious impact on outcomes in cutaneous melanoma, but the effects on outcome in MMHN remain undefined. This study aims to assess the outcome and identify clinical and histologic prognostic indicators in a recent cohort of patients with MMHN treated at a single institution. METHODS: The clinical records of 59 patients with the diagnosis of MMHN treated at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1978 and 1998 were retrospectively reviewed. Pathologic material on each of these patients was prospectively reviewed by at least two pathologists (MP, KB, or AH) for confirmation of diagnosis and assessment of histologic variables. Survival was calculated by the Kaplan-Meier method. Clinical (patient demographics, tumor characteristics, and treatment) and histologic data (tumor thickness, melanosis, melanoma in situ, vascular invasion, and multifocality) were analyzed for impact on outcome by both univariate and multivariate analyses. RESULTS: Thirty-five patients (59%) had sinonasal tumors (SNMM), whereas 24 (41%) had oral (ORMM) tumors. Forty-seven patients (79.6%) were staged as stage I, 8 (13.6%) as stage II, and 4 (6.8%) were classified as stage III. Regional lymphatic metastases at presentation were more frequent in ORMM compared with SNMM (25% vs 6%, p =.05). Surgery was used in all patients. Adjuvant radiation therapy was used more frequently in the SNMM group compared with the ORMM group (40% vs 17%, p =.04). The rates of local failure for ORMM and SNMM were 51% and 50%, nodal failure rates were 42% and 20%, and distant failure rates were 67% and 40%, respectively (p = NS). With a median follow-up of 20 months, the 5-year disease-specific survival rate was 44% (40% for ORMM vs 47% for SNMM, p = NS). Significant prognostic factors for disease-specific survival on univariate analysis included advanced clinical stage at presentation, tumor thickness greater than 5 mm, presence of vascular invasion, and development of nodal and distant metastases. On multivariate analysis, however, regional nodal failure lost significance. CONCLUSIONS: Clinical stage at presentation, tumor thickness greater than 5 mm, vascular invasion on histologic studies, and development of distant failure are the only independent predictors of outcome in MMHN.     

Cutaneous squamous cell carcinoma of the head and neck metastasizing to the parotid gland--a review of current recommendations

Cutaneous squamous cell carcinoma (SCC) of the head and neck may metastasize in up to 5% of patients, with the parotid lymph nodes the most frequent site for spread. Metastases frequently show delayed presentation after the primary cancer had been treated. The optimum treatment should be surgery followed by adjuvant radiotherapy, with an appropriate parotidectomy, and preservation of the facial nerve if not involved by tumor and treatment to the neck. In a clinically N0 neck, levels I to III should be cleared for facial primaries, levels II to III for anterior scalp and external ear primaries, and levels II to V for posterior scalp primaries. Approximate 5-year disease-specific survival (DSS) after treatment was 70% to 75%. Patients with immunosuppression, in particular transplant recipients, are at high risk of developing aggressive metastatic cutaneous SCC. Modifications of the staging systems have demonstrated the prognostic benefits of accurately staging parotid and/or neck nodal disease.     

Characterization and quantitative determination of impurities in piperaquine phosphate by HPLC and LC/MS/MS

Four impurities in piperaquine phosphate bulk drug substance were detected by a newly developed gradient reverse phase high performance liquid chromatographic (HPLC) method. These impurities were identified by LC/MS/MS. The structures of impurities were confirmed by spectroscopic studies (NMR and IR) conducted using synthesized authentic compounds. The synthesized reference samples of the impurity compounds were used for the quantitative HPLC determination. The system suitability of HPLC analysis established the validity of the separation. The method was validated according to ICH guidelines with respect to specificity, precision, accuracy and linearity. Forced degradation studies were also performed for piperaquine phosphate bulk drug samples to demonstrate the stability indicating power of the newly developed HPLC method.