Management of inverted papilloma of the nasal cavity and paranasal sinuses: importance of radiation therapy.

PURPOSE: Locally advanced inverted papilloma and inverted papilloma associated with squamous cell carcinoma are at high risk of local failure due to limitations of surgical resection resulting in repeat surgical procedures. The role of adjuvant radiation therapy is poorly defined. This study reviews a single institution experience of radiation therapy in the management of this disease. METHODS AND MATERIAL: Between 1977 and 1990 25 patients were treated at the Massachusetts General Hospital and the Massachusetts Eye and Ear Infirmary with radiation therapy for inverted papilloma (seven patients) and inverted papilloma associated with squamous cell carcinoma (18 patients) of the nasal cavity and paranasal sinuses. All patients presented with locally advanced invasive tumors; 5 of 7 with inverted papilloma had previous resections and 4 of 18 with associated squamous cell carcinoma had history of prior surgical excisions of inverted papilloma only (three patients) or inverted papilloma with squamous cell carcinoma in situ (one patient). Sixteen patients underwent radiation treatment following gross total resection, eight patients after subtotal tumor resection and one patient was inoperable by local invasion and received radiation therapy alone. RESULTS: Local control was achieved in 6 of 7 patients with inverted papilloma only and one patient required additional resection for persistent disease. Of 18 patients with associated squamous cell carcinoma, 17 were locally controlled after radiation therapy and one had persistent tumor. One patient failed locally 3 years after treatment. With a mean observation time of 4.8 years (range: 0.5-12.9 years) all seven (100%) patients with inverted papilloma only and 15 of 18 (83%) patients with associated invasive carcinoma are alive and without evidence of disease. Three patients with inverted papilloma associated with squamous cell carcinoma died, two patients as a result of their disease (one patient with persistent disease, one patient after local failure) and one patient of intercurrent disease. No failure in either regional lymph nodes or at distant sites was recorded. In the majority of cases radiation therapy was well-tolerated. CONCLUSIONS: Combined radiation therapy and surgery can offer excellent long-term control and should be considered in patients with history of recurrent disease, in the presence of suspected residual disease, after incomplete resection or for unresectable lesions. Patients with associated squamous cell carcinoma have a more aggressive course, however radiation therapy still has the prospect of permanent disease-free survival in patients who achieve local control.

Digitoxigenin 3-O-beta-D-furanosides.

The syntheses of the title compounds were accomplished by Koenig-Knorr condensation of acylated furanoses with digitoxigenin followed by basic hydrolysis of protecting groups. In this manner the riboside, 5-amino-5-deoxyriboside, 3,6-anhydroglucoside, and 3,6-dideoxy-3,6-iminoglucoside of digitoxigenin were prepared. These compounds as well as several of the synthetic intermediates showed weak to moderate cardiotonic activity.

Desensitization and functional antagonism by beta-adrenoceptor and muscarinic receptor agonists, respectively: a comparison with receptor alkylation for calculation of apparent agonist affinity.

1. Apparent affinity constants (KD) for prenalterol, an agonist of low intrinsic efficacy at beta 1-adrenoceptors in rat left atria, have been determined by use of receptor desensitization and functional antagonism induced by isoprenaline and carbachol, respectively. The values obtained have been compared to those values estimated with the irreversible beta-adrenoceptor antagonist, bromoacetylalprenololmenthane (BAAM). 2. The -log KD values for prenalterol estimated by desensitization or irreversible antagonism ranged from 6.8-7.1 and 6.2-7.1, respectively. 3. Carbachol produced functional antagonism of the response to prenalterol even though it was removed before addition of prenalterol. This effect was mediated by M2-muscarinic receptors. Pretreatment of animals with pertussis toxin did not affect the functional antagonism elicited by carbachol. The apparent KD value obtained after pre-exposure to carbachol (6.8) was similar to those estimated by use of either alkylation with BAAM or desensitization with isoprenaline (see above). 4. It is concluded that acute desensitization or functional antagonism of responses to agonists of low intrinsic efficacy provides a means to estimate apparent KD constants. This approach could be useful to characterize receptors for which an irreversible antagonist may not be available.

The interaction of methoctramine and himbacine at atrial, smooth muscle and endothelial muscarinic receptors in vitro.

1. The action of methoctramine and himbacine at muscarinic receptors has been studied using guinea-pig isolated trachea, oesophageal muscularis mucosae, paced left atria, and rat aortic preparations. 2. Methoctramine (1 x 10(-6)-3.2 x 10(-4) M), but not himbacine, elicited positive inotropic responses. These responses were enhanced by pretreating the animals with reserpine. The responses in reserpine-treated animals were not antagonized by phentolamine (1 x 10(-6) M) but were antagonized by propranolol (1 x 10(-6) M). 3. Methoctramine, but not himbacine, exhibited allosteric inhibitory effects at cardiac muscarinic receptors, resulting in a curvilinear Schild plot. Deviations from competitive antagonism were also observed in combination dose-ratio experiments using atropine and methoctramine. At 1 x 10(-6) M, the pKB value for methoctramine was 7.88 +/- 0.15 (mean +/- s.e.mean, n = 5). The pA2 value for himbacine at cardiac muscarinic receptors was 8.52 +/- 0.06 (n = 3). 4. At tracheal and oesophageal muscularis mucosal smooth muscle receptors, the Schild plots for both antagonists were linear. The pA2 values for methoctramine at receptors in these two preparations were similar (6.08 +/- 0.05 and 6.03 +/- 0.09 respectively, n = 4) and were approximately 60 fold less than those values observed at atrial receptors. Himbacine, also exhibited similar values at muscarinic receptors in the trachea and oesophageal muscularis mucosae (7.61 +/- 0.05 and 7.57 +/- 0.04 respectively, n = 4). 5. Muscarinic receptors mediating relaxation of the rat aortic endothelium exhibited pA2 values for methoctramine (5.87 +/- 0.12, n = 6) which were similar to those observed in the smooth muscle, but not the atria. The pA2 values for himbacine at endothelial muscarinic receptors were approximately 0.5 pA2 units lower than those observed at muscarinic receptors in smooth muscle (6.92 + 0.80, n = 6). In addition, the Schild slopes for methoctramine and himbacine at these receptors were significantly (P < 0.05) less than unity. 6. Methoctramine, and to a lesser extent himbacine, are potent and selective antagonists for cardiac muscarinic receptors. However, caution should be used in interpretation of the data with methoctramine in view of the inhibitory allosteric properties and direct inotropic actions of this compound.

Differential effects of pertussis toxin and lithium on muscarinic responses in the atria and ileum: evidence for receptor heterogeneity.

Pretreatment with pertussin toxin was shown to inhibit selectively muscarinic responses in the atria, but have no effect on responses in the ileum. The converse was true when the animals were pretreated with lithium. These data are consistent with the hypothesis that muscarinic receptors in the atria are coupled to an inhibition of adenylate cyclase, whilst those in the ileum are coupled to inositol phospholipid hydrolysis and indicate differences in the muscarinic receptors in these two tissues.

The interaction of parafluorohexahydrosiladiphenidol at muscarinic receptors in vitro.

1. The antagonistic actions of parafluorohexahydrosiladiphenidol (pFHHSiD) at muscarinic receptors has been studied in cardiac muscle, smooth muscle and cell culture preparations. In this paper, the classification scheme of Doods et al. (1987) is employed. This scheme is based upon differential affinities of muscarinic antagonists. pFHHSiD exhibited high pA2 values at M3 receptors mediating contractions of guinea-pig ileum and oesophageal muscularis mucosae (7.8 and 8.2 respectively) whereas low values were determined at M2 receptors mediating negative inotropic responses in guinea-pig atria (6.0). Intermediate pA2 values were determined at M1 receptors mediating contractions of the canine femoral and saphenous veins. 2. The pA2 values of pFHHSiD at receptors mediating endothelial-dependent relaxation of rat aortic rings, rabbit jugular vein and canine femoral artery (7.6-7.9) were similar to those determined on the ileum. However, the pA2 values of pFHHSiD at receptors mediating contractions of the guinea-pig trachea (7.1), which has been previously shown to possess M3 receptors, were different from those determined in the ileum. 3. The similarity in pA2 values of pFHHSiD between the M3 receptors in guinea-pig ileum and the receptors mediating endothelial-dependent relaxations provide further evidence for the role of M3 receptors in this vascular response. Taken together, pA2 values for pFHHSiD range from 7.1 to 8.2, depending upon the M3 preparation used. The selectivity of the compound therefore for the M3 versus the M2 muscarinic receptor ranged from 13 to 163 fold. 4. At muscarinic receptors mediating stimulation of phosphatidylinositol hydrolysis, pFHHSiD paradoxically displayed a high affinity for the M1 receptor in the SH-SY5Y cell line (pA2 = 7.9) as well as for the M3 receptor in the human astrocytoma (1321 NI cell line (pA2 = 7.6). The value at the M1 receptor in SH-SY5Y cells was greater than was observed at M1 receptors mediating contractions of both the canine saphenous and femoral veins (7.1). 5. pFHHSiD, therefore, clearly delineated M3 from M2 muscarinic receptors, whilst the separation between M1 and M3 receptors was variable. The reason for the anomalous affinity estimates in some functional studies remains unclear. These data indicate that the pA2 values for pFHHSiD appear to be tissue-dependent since the M3 selectivity varies according to the preparations studied. As a result the utility of pFHHSiD in muscarinic receptor classification is limited.

Frontal bone defect with frontal sinus mucopyocele.

For this patient's treatment, all three consultants advise against the Lynch-type frontoethmoidectomy procedure, with or without mucoperiosteal flap reconstruction of the nasofrontal duct. Treatment plan: Culture and sensitivity of pus; 2-3 weeks of intravenous antibiotics followed by osteoplastic flap fat obliteration of frontal sinus; delayed defect repair with methyl methacrylate (Montgomery). Trephination followed by treatment with local and systemic antibiotics (Donald); removal of infected bone and soft tissue (sinus collapse) and delayed defect repair in 6-12 months (Donald, Calcaterra) with metylmethacrylate (Donald) or in situ cured silicone elastomer (Calcaterra).

Cholesterol granuloma of the petrous apex: MR and CT evaluation.

We reviewed the clinical, CT, and MR findings in seven consecutive patients who had a total of nine cholesterol granulomas. Preoperative MR scans were available for five of the seven patients; two patients were studied with MR after treatment only (one had a recurrent lesion and the other was asymptomatic at the time of study). Preoperative CT scans were available for all patients, except one patient who was examined after developing a symptomatic recurrence. All lesions were detected by both imaging methods. Seven preoperative lesions (five patients) and one symptomatic recurrence (one patient) demonstrated increased signal intensity of both T1- and T2-weighted MR images. Three surgically drained lesions (three patients) showed a marked reduction in signal intensity on T1-weighted images. Pre- and postoperative lesions had different patterns of signal intensity on the chemical-shift images, which were obtained in two instances. The MR appearance of cholesterol granuloma differs from that of most other lesions that occur in the petrous apex. CT did not differentiate between pre- and postoperative lesions in all cases, while MR demonstrated a dramatic change on T1-weighted images and chemical-shift studies. Our findings indicate that MR is more specific than CT in suggesting the correct diagnosis of cholesterol granuloma and that MR appears to be the technique of choice in the follow-up of previously treated patients.

Deciding on optimal management of supraglottic carcinoma.

The management of supraglottic carcinoma is controversial. Laryngectomy with or without a radical neck dissection as the sole therapy is usually inappropriate. After supraglottic partial laryngectomy plus neck dissection, many patients are troubled with aspiration and often do poorly if postoperative radiation therapy is administered. Likewise, advocating radiation therapy alone for all lesions is inappropriate, although conventional once-daily radiation therapy is highly effective in eradicating early supraglottic carcinomas. However, for large T3 and T4 lesions, local control is poor with conventional radiation therapy. Thus these advanced lesions have been managed by total laryngectomy plus radiation therapy. To avoid loss of voice, a program of accelerated split fractionated radiation therapy was initiated at Massachusetts General Hospital in 1979. The results have shown marked improvement in local control of most moderately advanced supraglottic carcinomas.

Primary and secondary keratomas of the frontal sinus.

Keratomas in the paranasal sinuses have been described in the world literature with variable frequency and the inaccurate terminology of cholesteatoma. This paper describes an illustrative case and provides a discussion of the etiology and pathology of this disease. Because the pathologic findings are that of a true keratoma, classification of this disease as primary and secondary keratomas is recommended. The classification 1. primary keratoma is recommended for the epidermal cyst of congenital rest origin and 2. secondary keratoma is suggested for epithelial layers and cysts that are secondary to squamous cell implantation or migrations.

Manometric study of complete ostial occlusion in chronic maxillary atelectasis.

The effect of complete ostial occlusion on static pressure within the human maxillary sinus has not been previously studied. In this study, a novel way to directly determine maxillary sinus pressure is described. Maxillary sinus pressures were measured in five patients with chronic maxillary atelectasis (CMA); these values were compared to values obtained from the contralateral side and from patients with chronic sinusitis. Measurements were made by introducing an 18-gauge needle probe through the membranous fontanel of the maxillary sinus and recording the pressure value with an amplified, pressure-sensitive transducer. The average value recorded in five patients with atelectasis of the maxillary sinus and complete ostial occlusion was -8.4 +/- 2.6 cm H20 (mean +/- standard deviation). Static pressure measurements of the contralateral antrum were isobaric, as were measurements found in patients with chronic sinusitis. This study reports for the first time the sinus pressure of completely occluded maxillary ostia in patients with CMA. These results may improve our understanding of the development of ostial occlusion and its role in the pathogenesis of CMA and sinusitis.

Preservation of the facial nerve in the management of recurrent pleomorphic adenoma.

Whether to preserve or sacrifice a facial nerve involved with benign neoplasm is one of the most difficult intraoperative decisions confronting the head and neck surgeon. We reviewed 21 cases of recurrent pleomorphic adenoma treated with subtotal excision and facial nerve preservation, followed by postoperative radiation therapy. Of the 17 patients with microscopic residual tumor at completion of surgery, 16 (94%) remain free of recurrence with an average follow-up of 5.9 years. Only one of four patients (25%) with a large postoperative tumor load remains free of disease. Facial nerve function is normal in 20 of 21 patients. Preservation of the facial nerve with postoperative irradiation should be considered as an alternative to nerve sacrifice in selected cases of recurrent pleomorphic adenoma.

Evidence for laryngeal paralysis in cricoarytenoid joint arthritis.

OBJECTIVE/HYPOTHESIS: To demonstrate denervation atrophy of laryngeal muscles in a case of gout involving the cricoarytenoid joint. METHODS: The posterior cricoarytenoid (PCA) and arytenoideus (A) muscles from a 72-year-old man with extensive gout were compared with those from a normal adult larynx (age and sex unknown) using stereologic techniques for changes in muscle composition and fiber diameter. RESULTS: The PCA and A muscles in the gout specimen contained changes Indicative of muscle degeneration. In the PCA the volume fraction (VF) of intact muscle was 0.30, of degenerating muscle 0.13, and of fat 0.16. A normal PCA had a VF for intact muscle of 0.64 and 0 for degenerating muscle and fat. Similar changes were seen in the gout A muscle but were not measured. Muscle fiber diameters in the gout PCA (1,024 fibers) showed a significantly higher atrophy and hypertrophy factor than the normal PCA (1,255 fibers). The variability coefficient in the gout PCA (487) was almost double that in the normal PCA (290). Although muscle fiber diameters were not measured in the A muscle in gout, variability in fiber size was seen. CONCLUSIONS: The pattern and magnitude of muscle fiber degeneration in the PCA and A muscles from a larynx with gout fixation of the cricoarytenoid joint indicate neural degeneration. Since similar changes were not found in the thyroarytenoid (TA) and lateral cricoarytenoid (LCA), the neuropathy is selective for the posterior branch of the recurrent laryngeal nerve. This neuropathy is likely responsible for vocal cord adduction (stridor) and incomplete closure of the posterior commissure (aspiration) associated with acute cricoarytenoid arthritis. In chronic cricoarytenoid joint arthritis, ankylosis of the joint space maintains the adducted cord position.

Management of airway obstruction in cicatricial pemphigoid.

Cicatricial pemphigoid is a chronic vesiculobullous disease of the mucosal epithelium that primarily involves the oral cavity and the eyes. The clinical and histologic features are identical to those of bullous pemphigoid, and these features often can be nonspecific for other disease processes. It is not unusual for a period of 1 year or more to elapse before a diagnosis is made. The diagnosis of cicatricial pemphigoid requires characteristic lesions and histopathologic evidence of immunoglobulin deposition along the basement membrane, as well as a high index of suspicion. The authors detail a case of cicatricial pemphigoid resulting in airway obstruction and present the treatment required for both stabilization of the airway and resolution of the disease process.

Radiographic diagnosis, surgical treatment, and long-term follow-up of cholesterol granulomas of the petrous apex.

Cholesterol granuloma is an unusual lesion of the petrous apex. Accurate preoperative differentiation of the various lesions of the petrous apex by computed tomography scanning only has been difficult. We reviewed the clinical findings, computed tomography and magnetic resonance imaging scans, surgical approaches, and long-term follow-up in 10 patients with cholesterol granuloma of the petrous apex who were seen between 1971 and 1988. Headache and deficits of the 5th, 6th, 7th, and 8th cranial nerves were common presenting symptoms. Magnetic resonance imaging with special imaging techniques was accurate in diagnosing cholesterol granuloma in four patients preoperatively and three patients prior to revision surgery. The optimal surgical approach was chosen on the basis of clinical and radiographic findings and included the transsphenoidal, infralabyrinthine, transcochlear, and suboccipital routes. Our review reveals that magnetic resonance imaging is more specific than computed tomography in establishing a preoperative diagnosis and is also the technique of choice in follow-up. The long-term results are discussed.

Preservation of hearing in surgical removal of acoustic neuromas of the internal auditory canal and cerebellar pontine angle.

The surgical results in 69 patients with unilateral tumors of the cerebellopontine angle or internal auditory canal in whom total tumor removal was accomplished, and in whom an attempt was made to preserve hearing, are presented. The success rate of preservation of hearing and facial nerve function was correlated with the size of the tumor. Useful hearing, as defined by speech reception threshold no poorer than 70 dB and a discrimination score of at least 15%, was preserved in 73% of cases in which the tumor extension to the posterior fossa was no greater than 0.5 cm. In contrast, useful hearing was preserved in 22% of cases in which posterior fossa extension was greater than 2.5 cm. No significant correlation was found between preoperative evoked responses and success in preservation of hearing. The techniques and value of intraoperative monitoring of electrocochleogram (ECoG) and brain stem evoked responses are discussed. A theory of pathogenesis of intraoperative hearing loss, based on correlation of changes in evoked responses and simultaneous surgical events, is presented.

Preservation of hearing and facial nerve function in resection of acoustic neuroma.

The surgical results in 78 recent cases of total removal of unilateral acoustic neuroma in which an attempt was made to preserve cochlear function have been added to the authors' previous series of 66 cases to evaluate the factors influencing the ability to preserve useful hearing. Useful hearing was defined by speech reception threshold no poorer than 70 dB and a discrimination score of at least 15%. Analysis using a logistic regression model showed that certain preoperative clinical parameters such as tumor size, speech discrimination score, and gender were significantly correlated with hearing outcome. Favorable outcome was significantly correlated with smaller tumor size, higher preoperative speech discrimination score, and male sex. From this data, an explicit formula was devised for predicting hearing outcome for an individual patient. In four cases with useful hearing preserved, there was improvement of greater than 15 percentage points in speech discrimination scores. While preoperative auditory brainstem responses were not predictive of hearing preservation, monitoring of intraoperative auditory evoked potentials was predictive of hearing outcome in selected cases. Specifically, when wave V was unchanged at the end of the operation, even if it may have been transiently lost during surgery, useful hearing was invariably preserved.

The role of image-guidance systems for head and neck surgery.

BACKGROUND: Although image-guidance systems have gained widespread acceptance for neurosurgical procedures, their role for extracranial surgery of the head and neck is yet to be defined. OBJECTIVES: To describe the authors' experience with image-guidance systems and to measure the effects of image-guided technology on the performance of minimally invasive otolaryngological procedures. DESIGN: Prospective cohort study. METHODS: Optical- and electromagnetic-based image-guidance systems were used during the performance of endoscopic surgery on patients with disease of the paranasal sinuses, orbit, skull base, and temporal bone (n = 79). Results were compared with those in control patients who underwent similar surgery without image guidance during the same period (n = 42). RESULTS: Intraoperative anatomical localization was accurate to within 2 mm at the start of surgery in all cases. Accuracy degraded by 0.89 +/- 0.20 mm (mean +/- SE) during the operative procedure. The use of an image-guidance system increased operating room time by a mean of 17.4 minutes per case (image-guidance group, 137.3 +/- 6.0 minutes [mean +/- SE]; control group, 119.9 +/- 5.7 minutes; P=.006) and increased hospital charges by approximately $496 per case. Intraoperative blood loss (image-guidance group, 178.4 +/- 18.0 mL [mean +/- SE]; control group, 149.4 +/- 20.1 mL) and complication rates (image-guidance group, 2.7%; control group, 4.7%) did not differ significantly between groups. CONCLUSIONS: Image-guidance systems can provide the head and neck surgeon with accurate information regarding anatomical localization in cases with poor surgical landmarks caused by extensive disease or prior surgery; however, the use of such systems is associated with increased operative time and expense.

Validation of a voice outcome survey for unilateral vocal cord paralysis.

Current methods to assess voice outcomes in patients with unilateral vocal cord paralysis (UVCP) are limited by expense, reliability, or lack of a true patient-relevant focus. The purpose of this study was to develop and validate a patient-based, disease-specific instrument, the Voice Outcome Survey (VOS), that is brief, reliable, and sensitive to real clinical change in patients with UVCP. Fifty-six consecutive patients with uncompensated UVCP and without complicating comorbid illness received the VOS, the Medical Outcome Study Short Form 36-Item Health Survey (SF-36), and a voice laboratory analysis before and 6 months after type I thyroplasty. Overall, reliability of the VOS was excellent (r = 0.87, P < 0.0001). The VOS index was significantly (P < 0.05) correlated to subscales of the SF-36 including social functioning (SF) (r = 0.56) and physical role functioning (r = 0.35), as well as changes in objective voice measures such as phonation time (r = 0.51) and average intensity (r = 0.44). The VOS index was the most sensitive measure to clinical change after surgery (standardized response means: VOS, 1.92; phonation time, 0.68; SF, 0.58; physical role functioning, 0.53; intensity, 0.51). The VOS is a brief, valid, reliable, and highly sensitive measure of disease-specific health status in patients with UVCP.

Laryngeal paralysis--teflon injection.

This report is a review of the literature combined with the author's experience concerning Teflon injection of the larynx. Included are the etiology and diagnosis of vocal cord paralysis, indications and contraindications for Teflon injection of the larynx, its histopathology, pre- and postoperative management, proper and improper techniques for injecting Teflon, complications, and reasons for failure.