Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma.

Hereditary paraganglioma (PGL) is characterized by the development of benign, vascularized tumors in the head and neck. The most common tumor site is the carotid body (CB), a chemoreceptive organ that senses oxygen levels in the blood. Analysis of families carrying the PGL1 gene, described here, revealed germ line mutations in the SDHD gene on chromosome 11q23. SDHD encodes a mitochondrial respiratory chain protein-the small subunit of cytochrome b in succinate-ubiquinone oxidoreductase (cybS). In contrast to expectations based on the inheritance pattern of PGL, the SDHD gene showed no evidence of imprinting. These findings indicate that mitochondria play an important role in the pathogenesis of certain tumors and that cybS plays a role in normal CB physiology.

Adjuvant chemotherapy for high-risk squamous-cell carcinoma of the head and neck.

A prospective clinical trial was developed to evaluate efficacy, toxicity, and patient compliance to adjuvant chemotherapy following surgery and postoperative radiation therapy in patients with squamous-cell carcinoma of the head and neck with extracapsular spread of tumor in cervical metastases. Following postoperative radiation therapy, 18 courses of methotrexate (MTX) and 5-fluorouracil (5-FU) were administered over 6 months. Fifty patients were registered. A total of 771 doses were administered. Dose reduction was required 72 times. Therapy was stopped in one patient (2%) because of toxicity. Three patients (6%) refused to complete the adjuvant therapy. Adjusted 2-year no evidence of disease (NED) survival is 66%. This study demonstrates that patients with advanced squamous-cell carcinoma of the head and neck can undertake an aggressive program of adjuvant MTX/5-FU with acceptable compliance and toxicities. Preliminary data generated in this nonrandomized study support the call for a prospective randomized multiinstitutional trial of this program.

Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas.

BACKGROUND: Paragangliomas are rare and highly heritable tumours of neuroectodermal origin that often develop in the head and neck region. Germline mutations in the mitochondrial complex II genes, SDHB, SDHC, and SDHD, cause hereditary paraganglioma (PGL). METHODS: We assessed the frequency of SDHB, SDHC, and SDHD gene mutations by PCR amplification and sequencing in a set of head and neck paraganglioma patients who were previously managed in two otolaryngology clinics in the USA. RESULTS: Fifty-five subjects were grouped into 10 families and 37 non-familial cases. Five of the non-familial cases had multiple tumours. Germline SDHD mutations were identified in five of 10 (50%) familial and two of 37 ( approximately 5%) non-familial cases. R38X, P81L, H102L, Q109X, and L128fsX134 mutations were identified in the familial cases and P81L was identified in the non-familial cases. Both non-familial cases had multiple tumours. P81L and R38X mutations have previously been reported in other PGL families and P81L was suggested as a founder mutation. Allelic analyses of different chromosomes carrying these mutations did not show common disease haplotypes, strongly suggesting that R38X and P81L are potentially recurrent mutations. Germline SDHB mutations were identified in two of 10 (20%) familial and one of 33 ( approximately 3%) non-familial cases. P131R and M71fsX80 were identified in the familial cases and Q59X was identified in the one non-familial case. The non-familial case had a solitary tumour. No mutations could be identified in the SDHC gene in the remaining four families and 20 sporadic cases. CONCLUSIONS: Mutations in SDHD are the leading cause of head and neck paragangliomas in this clinic patient series. SDHD and SDHB mutations account for 70% of familial cases and approximately 8% of non-familial cases. These results also suggest that the commonness of the SDHD P81L mutation in North America is the result of both a founder effect and recurrent mutations.

Transantral-ethmoidal decompression of optic canal fracture.

A case of indirect trauma to the optic nerve was successfully treated with transethmoidal decompression. The literature was reviewed, and reports of poor results from neurosurgical procedures are cited. Improved results from transethmoidal decompression of the optic nerve have been reported by Japanese authors but, in our opinion, without proper selection of cases. Early diagnosis of traumatic compression of the intracanalicular optic nerve as evidenced by delayed and/or progressive vision loss following injury, coupled with prompt transantral-ethmoidal surgical decompression, should yield gratifying results in the treatment of this uncommon condition.

Angiosarcoma of the maxillary sinus: literature review and case report.

A rare case of angiosarcoma of the maxillary sinus is reported. Review of the literature concerning angiosarcoma of the head and neck revealed 14 previously published cases involving the nose, nasal sinuses, and nasopharynx. Angiosarcoma of the skin and soft tissues of the head and neck differs in behavior from that affecting the nose, nasal sinuses, and nasopharynx. The case reported presents the protracted clinical course of this malignant tumor.

Pulmonary lymphangitic carcinomatosis from hypopharyngeal adenosquamous carcinoma.

Although pulmonary lymphangitic carcinomatosis (PLC) is not uncommon for breast, bronchial, and stomach cancers, it is rarely associated with head and neck malignancy. A case of PLC is reported with the primary lesion being an adenosquamous carcinoma of the hypopharynx. A literature review is discussed, highlighting the varied radiographic picture of PLC, the possible diagnostic modalities, the proposed pathogenesis, and the treatment options. The prognosis even if antemortum diagnosis and treatment are given remains fatal, although with temporary improved quality of life and lengthened survival. There is hope that with greater awareness of the disease process an increased incidence of diagnosis may allow progress to be made in therapeutic interventions.

Base of tongue salivary gland tumors.

Salivary tumors of the base of the tongue are encountered infrequently. A retrospective review of medical records from 1955 to 1985 was undertaken to determine the incidence of occurrence and to assess the outcome of the therapy provided. One hundred seventy-eight minor salivary gland tumors of the oral cavity and oropharynx were identified, of which 22 (13%) were located in the tongue base. All were malignant. The most common histologic type was mucoepidermoid carcinoma (10 patients), followed by adenocarcinoma (6 patients), and adenoid cystic carcinoma (6 patients). Thirteen patients were available for a mean follow-up of 5 years. Treatment was most often a combination of wide resection combined with postoperative radiation therapy. Ten patients (77%) are alive, one with persistent disease 8 years after diagnosis. Three patients died within 2 years of diagnosis, one with intercurrent disease. Improved control of disease in this series, when compared to previously reported series, is attributed to adequate surgical therapy and adjuvant radiotherapy. The deaths in our series occurred in patients who were unable to proceed with the recommended therapy. These unusual lesions require aggressive multimodality treatment for improved survival.

Cisplatin--5-fluorouracil chemotherapy for advanced inoperable squamous carcinoma of the head and neck.

Patients with locally advanced, inoperable squamous cell carcinoma of the head and neck were offered three courses of cisplatin and 96-h 5-fluorouracil (5-FU) infusion. Subsequent therapy included surgery when feasible, irradiation therapy, and a maintenance program of methotrexate (MTX)-5-FU. Thirty-three patients were evaluated prospectively. Seven patients underwent a single course of chemotherapy. Five patients underwent two courses of chemotherapy. Twenty-one patients underwent three courses of adjuvant chemotherapy. The overall response rate was 48% (16 of 33). Fifteen of 21 patients (76%) receiving three courses of chemotherapy evidenced a response; this included three complete responses (CRs) (9%). No responses were seen in patients receiving only one or two courses of chemotherapy. Among responding patients, the initial favorable response to chemotherapy was apparent after the first course of chemotherapy. Patients who failed to demonstrate any response after two courses of chemotherapy did not respond after a third course. A significant group of patients fail to respond and should be offered participation in other investigational protocols as they become available.

Early complications of tracheotomy. Incidence and management.

Tracheotomy is associated with multiple and potentially life-threatening complications even under elective conditions. Minor bleeding, tube displacement or obstruction, subcutaneous emphysema, and pneumothorax are the most commonly encountered complications. Attention to details and the availability of adequate instrumentation, lighting, and trained personnel are essential to minimize morbidity.

Cervical lymph node metastasis after local excision of early squamous cell carcinoma of the oral cavity.

A total of 54 patients with stage I and stage II squamous cell carcinoma of the oral cavity were reviewed as to treatment modality, adequacy of treatment, and site of failure. Surgery was employed as the sole initial treatment modality in 52 patients. Forty-three underwent primary tumor excision alone and 9 underwent elective neck dissection at the time of primary tumor excision. The patients who underwent elective neck dissection at the time of excision of the primary tumor had a 3 year survival rate of 88 percent, in comparison to a survival rate of 77 percent in those patients whose initial therapy was directed solely at the primary tumor. A low incidence of local recurrence (2 percent) and a high incidence of neck recurrence (42 percent) were documented in those patients treated by primary tumor excision alone. Patients who underwent salvage neck dissection for recurrent neck node metastases had a 3 year survival rate of 56 percent. This study has documented a high incidence of cervical node recurrence in patients with T1 and T2 squamous cell carcinomas of the oral cavity treated by primary tumor excision alone and a poor survival rate after salvage therapy. A small group of patients who underwent elective neck dissection had a demonstrably high survival rate. These observations lend support to the call for elective neck dissection in patients with stage I and II oral cavity carcinoma but are not conclusive. Therapeutic decisions regarding elective treatment of the neck will continue to be made according to the best judgment and prejudices of the individual surgeon until a prospective, randomized multi-institutional study addressing this specific issue is undertaken.

Malignant neoplasms of the hard palate and upper alveolar ridge.

Malignant neoplasms of the hard palate and upper alveolar ridge can arise from the epithelial (mucosal), salivary, hematopoietic, or mesenchymal tissues in this region. Unlike other regions in the head and neck, only about two thirds of malignant neoplasms of the hard palate are squamous cell carcinomas, and few large series have reported treatment protocols and outcomes for patients with these tumors. In this review, we will describe our series of 51 patients with malignant neoplasms of the hard palate and upper alveolar ridge. This review will emphasize the surgical treatment program and rehabilitative techniques developed at the University of Pittsburgh.

Treatments of choice for early carcinoma of the oral cavity.

The treatment of squamous cell carcinoma of the oral cavity is determined primarily by the stage of the disease. Therapeutic modalities include surgery, radiation therapy, and chemotherapy. For patients with small, localized primary lesions and no metastases (Stages I and II), treatment might include resection of the primary tumor with or without elective neck dissection, radiotherapy to the primary tumor with or without elective neck irradiation, or combination therapy including resection of the primary tumor followed by irradiation of the neck. Patients presenting with clinically negative necks who are initially treated with elective neck dissections show better survival rates than similar patients undergoing later salvage neck dissections.

Management of tumors of the parapharyngeal space.

Benign and malignant tumors can arise from any of the structures contained within the parapharyngeal space. Such tumors are very rare, however. Also, malignant tumors from adjacent areas (eg, the pharynx) can extend into the parapharyngeal space by direct growth, or distant tumors may metastasize to the lymphatics within the space. Although the history and physical examination can provide clues to the site of origin and nature of a parapharyngeal space tumor, imaging studies are more useful for defining the site of origin and extent of the mass, as well as its vascularity and relationship to the great vessels of the neck and other neurovascular structures. Surgery is the mainstay of treatment. The surgical approach chosen should facilitate complete tumor extirpation with minimal morbidity. Irradiation is administered as primary therapy in patients with unresectable tumors, poor surgical candidates, and selected other patients. Radiation therapy is also used after surgery for high-grade malignancies or when wide surgical margins cannot be achieved.

Microvascular free tissue transfer for reconstruction of head and neck cancer defects.

Over the last 10 years, microvascular free tissue transfer techniques have broadened the range of the head and neck surgeon, allowing for successful reconstruction of extensive curative extirpations in one operation with minimal morbidity. Success rates of more than 90% are now being achieved consistently. This article provides an overview of these revolutionary techniques for oral cavity, mandibular, and hypopharyngeal reconstructions. Patients are selected for microvascular free tissue transfer because of the large size of their defect, its location (eg, anterior mandibular loss), or complexity (circumferential defects of the hypopharynx). Others may be good candidates for this surgery because of previous radiotherapy or failed reconstructive surgery. Donor sites range from the radial forearm to the jejunum.

Management of carcinoma of the supraglottic larynx: evolution, current concepts, and future trends.

The treatment of cancer of the supraglottic larynx has undergone an evolution. Better understanding of the anatomy and biology of cancer in this anatomic site has enabled surgeons to devise effective oncologic strategies while making every effort to preserve the function of the larynx. Certain recent concepts and changing trends have emerged in the treatment of cancer of the supraglottic larynx, including the treatment of the neck, significance of extracapsular spread of tumor in cervical lymph nodes, and conservation laser surgery. In 1985, Snyderman et al. reported the prognostic significance of extracapsular spread in patients with cancer of the supraglottic larynx. In 1990, Lutz et al. reported the results of our experience with the treatment of 202 patients. The review verified the significant risk of bilateral neck disease in these patients, even with adjuvant radiation therapy. Accordingly, since 1990 all patients having cancer of the supraglottic larynx have been treated in the Department of Otolaryngology at the University of Pittsburgh with bilateral neck dissections. The use of adjuvant radiation therapy has been based on the presence of extracapsular spread. This study documents the oncologic effectiveness of this treatment and confirms the efficacy of bilateral neck dissections in an attempt to control neck disease and the prognostic significance of extracapsular spread. We review the evolution of the treatment of cancer of the supraglottic larynx, present our results, and consider innovative surgical approaches.

Management of chylous fistulas;.

Chylous fistula following radical neck dissection is a disturbing and potentially serious complication. Meticulous surgical technique in the areas of the thoracic duct on the left and the lymphatic ducts on the right will usually prevent the occurrence of a chylous leak. If one should develop, however, a pressure dressing alone is usually not sufficient to tamponade the leaking vessel. The patient should be returned to the operating room where the leak is identified and ligated. Loss of chyle from the body will rapidly deplete the body stores of fluid, proteins, and electrolytes. Careful monitoring of serum electrolytes and proteins and accurate replacement of these substances is essential. The anatomy, physiology, surgical technique, and treatment of the lymphatics and chylous fistulas at the base of the neck are considered herein.

Intratracheal thyroid.

Ectopic thyroid tissue within the trachea (intratracheal or endotracheal tissue) is a rare cause of upper airway obstruction. The symptoms may be classical or, as in most cases in which the voice is not affected, the first sign may be a wheeze. This may result in the symptoms being mistaken for asthma. The presence of a submucosal upper tracheal mass is quite unusual. If one is familiar with the fact that thyroid tissue may occur in this location, then this diagnosis should be considered in patients with such symptoms, and the appropriate diagnostic studies and surgical management should be instituted. The present case report entailed a 56-year-old female who was admitted to the hospital after having been treated for a year in an outlying area. She had increasing shortness of breath and wheezing and had been treated several times for asthma. Indirect laryngoscopy revealed an upper tracheal submucosal mass which was confirmed by direct laryngoscopy and by tomography. Biopsies were taken confirming nodular ectopic thyroid tissue. The patient was operated on through a cervical incision and a tracheal flap was elevated in order to carry out a submucosal dissection of this mass. The patient has done well for more than a year following surgery, and histologically this lesion was benign in the thyroid tissue.

Lymphangiomatous macroglossia.

Lymphangiomatous macroglossia, or giant tongue, usually presents within the first two years of life. The tongue enlarges to the point of protrusion from the mouth with resultant ulceration and frank necrosis of the tip. There may be associated malocclusion and prognathia produced by the enlargement of the tongue. The pathology and clinical manifestations of lymphangioma of the tongue are discussed in this paper, and a case report is presented.

Rhabdomyoma of the pharynx.

The occurrence of a large pharyngeal rhabdomyoma in an otherwise healthy adult male is discussed in this paper. This lesion, except for local symptomatology, is established as benign. A differential diagnosis, as well as the specific surgical approach to its removal, are also presented.

The surgical management of chronic parotitis.

Chronic parotitis is a disorder characterized by recurrent painful swelling of the gland with purulent sialorrhea. Occasionally, the condition fails to respond to medical management and definitive surgical therapy is necessary. Sialolithiasis is the usual etiology in cases of parotitis, although occasionally severe recurrent parotid infections are superimposed on underlying Sjögren's disease. Total parotidectomy with facial nerve dissection has been used in such cases in our department and has proved to be an excellent way to manage this disease. A summary of our results indicate that the recurring infections were eradicated and that the complication rate is tolerable, considering the magnitude of the problem. We feel that it is better to use surgical management early rather than wait for the formation of fistulae or abscesses.