Donald T. Donovan

Botulinum toxin treatment of cranial-cervical dystonia, spasmodic dysphonia, other focal dystonias and hemifacial spasm.

In the past five years, 477 patients with various focal dystonias and hemifacial spasm received 3,806 injections of botulinum A toxin for relief of involuntary spasms. A definite improvement with a global rating greater than or equal to 2 on a 0-4 scale, was obtained in all 13 patients with spasmodic dysphonia, 94% of 70 patients with blepharospasm, 92% of 13 patients with hemifacial spasm, 90% of 195 patients with cervical dystonia, 77% of 22 patients with hand dystonia, 73% of 45 patients with oromandibular dystonia, and in 90% of 21 patients with other focal dystonia who had adequate follow up. While the average duration of maximum improvement lasted about 11 weeks after an injection (range seven weeks in patients with hand dystonia to 15 weeks in patients with hemifacial spasm), some patients benefited for over a year. Only 16% of the 941 treatment visits with follow up were not successful. Except for transient focal weakness, there were very few complications or systemic effects attributed to the injections. This study supports the conclusion that botulinum toxin injections are a safe and effective therapy for patients with focal dystonia and hemifacial spasm.

Multiple Endocrine Neoplasia Type 2a Associated with Cutaneous Lichen Amyloidosis

PURPOSE To describe and characterize the association of hereditary cutaneous lichen amyloidosis with multiple endocrine neoplasia type 2a (MEN 2a). DESIGN Survey of a family for two diseases. SETTING Evaluation of patients at a clinical research center. PATIENTS Nineteen family members with MEN 2a. MEASUREMENTS AND MAIN RESULTS In this family cutaneous lichen amyloidosis presented as multiple infiltrated papules overlying a well-demarcated plaque in the scapular area of the back (right or left). Immunohistochemical studies showed amyloid that stained for keratin but not calcitonin. Three family members had the characteristic skin lesion and also carried the gene for MEN 2a; two additional members carried the gene for MEN 2a, but did not manifest the observable skin changes associated with lichen amyloidosis. CONCLUSIONS From the findings in this kindred and in another recently reported but unrelated family with an identical type of pruritic skin rash and MEN 2a, several conclusions can be drawn. First, the syndrome of cutaneous amyloidosis and MEN 2a is a clearly defined autosomal dominant hereditary syndrome. Second, the dermal amyloid appears to be caused by deposition of keratin-like peptides rather than by calcitonin-like peptides. Third, known families with hereditary lichen amyloidosis should be screened to determine the true frequency of this syndrome.

Does the severity of sinus computed tomography findings predict outcome in chronic sinusitis

OBJECTIVES: We studied the association between the severity of pretreatment CT scan findings and the improvement in symptoms of chronic sinusitis after treatment. METHODS: We analyzed data from an ongoing prospective, nonrandomized clinical outcomes study of patients treated for chronic sinusitis at a tertiary-care academic medical center (n = 57, mean age 46.8 years). Disease-specific symptom severity was measured with a validated health status instrument, and CT stage was quantified with the Harvard CT staging system. RESULTS: In a multivariate analysis, symptom severity based on CT findings emerged as a strong predictor of both improvement in symptom score outcome (β = 0.47, P = 0.01) and absolute symptom level after treatment (P = −0.58, P = 0.001). CONCLUSIONS: Severity as assessed by a pretreatment CT scan is a strong predictor of outcome. Patients with higher symptom severity based on CT scans showed significantly larger improvement and lower absolute levels of symptom severity after treatment. This study links CT scan findings and subjective patient-based outcomes (symptom scores) using a validated outcomes instrument.

Molecular transformation of recurrent respiratory papillomatosis: viral typing and p53 overexpression.

Recurrent respiratory papillomatosis (RRP) is a histologically benign disease of the larynx, trachea, and bronchi. Here we report on the histologic and molecular characteristics of 7 cases of malignant transformation of RRP to squamous cell carcinoma (SCCA). The clinical histories of 7 patients with RRP who developed SCCA were carefully reviewed. Sequential biopsies were available from 5 of the 7 cases of spontaneous transformation of RRP to SCCA and were reviewed. In addition, p53 protein overexpression and human papillomavirus (HPV) typing for all cases was examined. The average age of patients with juvenile-onset RRP was 3 years, and that of patients with adult-onset RRP was 31 years. The average age of onset of transformation to SCCA was 28 years. All patients had laryngeal involvement with RRP, and 3 of the 7 patients had tracheal extension of disease. Five patients were tracheotomy-dependent. Four of the 7 patients developed SCCA of the lung, while 3 patients developed laryngeal SCCA. There was no consistent histologic progression from squamous papilloma to papilloma with dysplasia, and all but 1 of the SCCAs were well differentiated. The overexpression of p53 protein was variable in each of the 5 patients. We detected HPV types 6/11 in papillomas from 3 patients, and HPV types 6/11, 16/18, and 31/33/51 in a papilloma of a fourth patient. No HPV DNA was detected in papillomas of 2 patients. We found HPV 6/11 in 4 of the carcinomas. We conclude that the spontaneous transformation of RRP to SCCA is not characterized by a histologic progression through dysplasia over time. Transformation can result in the loss of HPV expression. It does not appear that p53 is a molecular marker for monitoring the transformation process. Thus, these cancers may be very difficult to diagnose histologically and clinically early in the course of the transformation of the disease.

The use of intensity modulated radiotherapy for the treatment of extensive and recurrent juvenile angiofibroma.

These case series are presented to describe the application and advantages of intensity modulated radiotherapy (IMRT) for the treatment of extensive and/or recurrent juvenile angiofibroma. Two patients were diagnosed with recurrence at 11 and 13 months postoperatively, and one was surgically unresectable. The affected areas included the base of skull, cavernous sinus, pterygopalatine fossa, infratemporal fossa, posterior orbit and nasopharynx. Highly conformal IMRT was delivered with limited radiation doses to the optic nerves, optic chiasm, brainstem, brain, spinal cord, lens, retina, mandible, and parotid. The total dose delivered to the tumor varied from 3400 to 4500 cGy. The tumor shrunk radiographically in all three cases and there was no endoscopic evidence of disease in two cases at 15 months and 40 months. There was no acute toxicity. Late toxicity was limited to one episode of epistaxis and persistent rhinitis in one patient. In conclusion, IMRT provides several advantages over conventional radiotherapy in the treatment of recurrent juvenile angiofibroma.

Endoscopic management of Zenker's diverticulum: factors predictive of success or failure.

Objectives: We review our experience with endoscopic management of Zenkers diverticulum. We sought to analyze and determine risk factors for success or failure of endoscopic diverticulum treatment. Methods: We performed a retrospective review of 72 consecutive patients who underwent attempted endoscopic management of a Zenkers diverticulum between January 2000 and April 2006. The procedures were performed by either of 2 otolaryngologists. There were 50 men and 22 women ranging in age from 44 to 93 years. A total of 85 procedures were performed. The medical records were reviewed for preoperative diverticulum size (small, 1 to 2 cm; moderate, 2.1 to 3.0 cm; and large, more than 3.0 cm), intraoperative diverticulum characteristics, patient anatomic limitations that prevented adequate endoscopic visualization, surgical complications, and management of recurrences. Results: Of our 72 patients, 61 (85%) were able to undergo endoscopic cricopharyngeal myotomy with diverticulum elimination. Of the 61 endoscopic procedures, 47 (77%) resulted in complete symptom resolution. The most common risk factors for recurrence were diverticulum size (more than 3 cm) and amount of redundant mucosa. Of the 14 patients with a recurrence, 10 (71%) underwent a repeat procedure. Six of the 14 (43%) had a successful excision via a cervical approach, and 4 of the 14 (29%) underwent a repeat endoscopic myotomy. There was 1 major complication (esophageal tear), and there were 3 minor complications (mucosal abrasions). Conclusions: Most patients with a Zenkers diverticulum are good candidates for endoscopic management. In our series, 84% of those who underwent endoscopic treatment ultimately achieved relief of symptoms. The patient morbidity is minimal. A large diverticulum with redundant mucosa is a risk factor for recurrence after endoscopic treatment.

Life-threatening presentations of fibrovascular esophageal and hypopharyngeal polyps.

Giant fibrovascular polyps of the esophagus and hypopharynx are benign tumors of the upper digestive tract Although a rare cause of asphyxiation, laryngeal impaction by a regurgitated polyp of the esophagus may be the initial symptom that brings the patient to request medical attention. Two new cases of giant fibrovascular polyps with dramatic and potentially life-threatening presentations illustrate the unpredictable behavior of these unusual tumors. Both patients presented to the emergency center with a history of coughing and eructation followed by temporary airway obstruction that was relieved by clenching a regurgitated fleshy mass between the teeth. Diagnostic and therapeutic intervention requires aggressive airway management, radiographic and endoscopic evaluation, and definitive surgical treatment. Tracheotomy was required in one patient, and successful endotracheal intubation provided satisfactory airway control in the second. Esophagoscopy revealed the origin of both tumors to be near the cricopharyngeal muscle. Complete surgical excision was curative in both cases.

Causes and consequences of adult laryngotracheal stenosis

Laryngotracheal stenosis (LTS) is largely considered a structural entity, defined on anatomic terms (i.e., percent stenosis, distance from vocal folds, overall length). This has significant implications for identifying at‐risk populations, devising systems‐based preventive strategies, and promoting patient‐centered treatment. The present study was undertaken to test the hypothesis that LTS is heterogeneous with regard to etiology, natural history, and clinical outcome.

Interferon alfa-n1 (Wellferon) in juvenile onset recurrent respiratory papillomatosis: results of a randomized study in twelve collaborative institutions.

Sixty‐six patients with clinically severe juvenile‐onset recurrent respiratory papillomatosis (RRP) were entered into a 12‐month randomized crossover study to evaluate interferon alpha‐n1 Wellferon® (WFN) as an adjuvant to CO2 laser surgical excision. Eligibility required disease onset to be before age 16, and an endoscopic excision requirement of at least three operations in the 6 months immediately prior to entry. Patients were randomized to Observation versus WFN at a dose of 5 MU/m2 daily for 28 days and three times weekly for 5 months. The patient groups were comparable in extent of disease at entry. Total extent of disease was determined by a composite score derived from the number of diseased anatomic sites and extent of surface area and lumen encroachment present at each site. Standard endoscopic excisions were performed every 2 months and clinical courses compared on a basis of composite scores determined at each endoscopy. Statistically significant improvement occurred in the patient group which received WFN. We conclude that interferon alpha n‐1 is an effective adjuvant to surgery in RRP management.

Oncocytic mucoepidermoid carcinoma of the salivary glands.

Two parotid mucoepidermoid carcinomas with predominant oncocytic features were initially assessed on frozen section. Because of extensive oncocytic change, it was inferred that the lesions were most likely benign. Permanent sections revealed low-grade mucoepidermoid carcinoma with prominent oncocytic change (in more than 75% of the neoplasms) in both cases. Review of 48 additional consecutive cases of mucoepidermoid carcinoma of the salivary glands revealed prominent oncocytic change (accounting for 60% of the neoplasm) in one high-grade lesion. Phosphotungstic acid-hematoxylin stains revealed strong granular cytoplasmic staining in the oncocytic elements; immunohistochemical stains for antimitochondrial antibodies also showed intense immunoreactivity in these cells. Oncocytic change is not typically a prominent feature of mucoepidermoid carcinoma of the salivary glands, and to our knowledge, only three such cases have been reported previously. Because most salivary gland lesions with oncocytic change are benign, it is important to distinguish mucoepidermoid carcinoma from other entities that may show prominent oncocytic change. We report three additional examples of this rare lesion, two low-grade tumors and one high-grade tumor, and review our experience with oncocytic change in mucoepidermoid carcinoma of the salivary glands.