Biomedical subjects
Publications and source records attributed to T V McCaffrey.
Paragangliomas of the head and neck are derivatives of neural crest cells, comprising part of the diffuse neuroendocrine system. Indeed, paragangliomas encompass a unique subset of tumors of the head and neck. Their biochemistry and physiology are similar to other neuroendocrine tumors unlike tumors based on location. This article discusses their distinct biologic attributes.
OBJECTIVES: Recovery of injured peripheral nerves depends on a balance between Schwann cell regeneration and scar formation. Transforming growth factor-beta1 (TGF-beta1) has been implicated as a humoral stimulus in scar formation. The neutralization of TGF-beta1 has been beneficial in the reduction of fibrosis. This study was to identify the presence of TGF-beta1 in regenerating peripheral nerve and to measure motor nerve regeneration by the neutralization of TGF-beta1 in neural wounds. STUDY DESIGN: A randomized study of rat sciatic nerve regeneration. METHOD: Sciatic nerve axotomy was performed, followed by serial immunohistochemical staining by anti-TGF-beta1 at 12 to 216 hours (n = 5). Two groups (n = 10) with sciatic axotomy and epineural repair were treated with a 7-day perineural administration of neutralizing antibody of TGF-beta1 or saline carrier via subcutaneous silicone infusion port. A control group (n = 10) without axotomy with anti-TGF-beta1 administration was established. At 12 weeks the compound muscle action potential amplitude (CMAP) and the muscle twitch strength generated by the gastrocnemiussoleus muscle complex were measured. RESULTS: TGF-beta1 was qualitatively present with maximal concentration by 72 to 144 hours. CMAP amplitude in the anti-TGF-beta1/axotomy group was 49.6% of the control and the axotomy/saline group was 31% of the control. Muscle twitch strength was 74% and 46.5%, respectively. These differences were statistically significant, P = .05. CONCLUSIONS: The presence of TGF-beta1 at regenerating nerve sites was confirmed. The benefit of neutralization of transforming growth factor on CMAP and muscle twitch strength was shown. These results suggest improved regeneration at nerve injury sites with neutralization of TGF-beta1.
PURPOSE: The purpose of this retrospective study is to present the results of postoperative adjuvant radiotherapy after primary surgery for squamous cell carcinoma of the tongue base and to compare these results to those obtained with surgery alone. METHODS: Between 1974 and 1993, continuous-course postoperative radiotherapy was delivered to 24 patients (Adjuvant Radiotherapy Group). Results were compared to those from a group of 55 patients treated with surgery alone (Surgery Group). RESULTS: Characteristics of the two groups were similar, except that a larger proportion of patients in the Adjuvant Radiotherapy Group had higher pathologic TNM stages. Ipsilateral neck control (87% vs. 68%, p = 0.04), contralateral neck control (100% vs. 76%,p = 0.002), relapse-free survival (64% vs. 46%,p = 0.04), and control above the clavicles (80% vs. 48%, p = 0.007) were significantly higher in the Adjuvant Radiotherapy Group compared to those in the Surgery Group (5-year figures shown). CONCLUSION: The use of adjuvant radiotherapy after surgical resection of tongue base squamous cell carcinoma significantly decreased the rate of local-regional recurrence and improved relapse-free survival compared with surgery alone but did not alter cause-specific or overall survival.
PURPOSE: The purpose of this study was to determine the efficacy of postoperative adjuvant radiation therapy with regard to reducing the rate of recurrence in the neck, cancer-related death, and death from any cause in patients with squamous cell carcinoma of the head and neck region metastatic to neck nodes. METHODS: This was a retrospective review of patients with pathologically confirmed nodal metastases who underwent neck dissection and postoperative adjuvant radiation therapy for squamous cell carcinoma of the head and neck region. Time to recurrence in the dissected area of the neck, any recurrence in the neck, cancer-related death, and death from any cause were estimated with the Kaplan-Meier method. A matched-pair analysis was performed utilizing a cohort of patients who underwent neck dissection without postoperative radiation therapy. The patients from the two cohorts were matched according to previously reported high-risk features for cancer recurrence and death. Cox hazards models for the matched pairs were used to evaluate the relative risk of subsequent recurrence in the dissected side of the neck, any neck recurrence, cancer-related death, and overall survival. MATERIALS: The medical records and pathologic slides of 95 consecutive patients with pathologically confirmed nodal metastases from squamous cell carcinoma of the head and neck region who underwent neck dissection and postoperative adjuvant radiation therapy between January 1974 and December 1990 were reviewed. Previously published data from 284 patients with squamous cell carcinoma of the head and neck region treated with neck dissection alone between January 1970 and December 1980 were used for a matched-pair analysis. RESULTS: The relative risks for recurrence in the dissected side of the neck, any neck recurrence (dissected neck or delayed undissected neck metastasis), cancer-related death, and death from any cause for patients treated with operation alone relative to those treated with operation and postoperative radiation were 5.82, 4.72, 2.21, and 1.67, respectively. CONCLUSION: This study provides evidence that postoperative adjuvant radiation therapy for the high-risk neck can reduce the rate of recurrence within a dissected neck, delayed metastasis within an undissected neck, cancer-related death, and death from any cause.
Glass ionomer cements were first described by Wilson and Kent and have been used in dentistry since 1969. It has been recommended for bridging ossicular chain defects, fixation of ossicular chain prosthesis, anchoring of cochlear implants, mastoid obliteration, and repair of tegmen and posterior canal wall defects. The biocompatability and stability of this material over time is vital to its usefulness in neurotologic surgery. The purpose of this study was to assess the stability of a glass ionomer cement in the presence of bacteria and in different pH environments. We demonstrated that bacteria readily adhere to the surface and their presence is associated with accelerated loss of matrix. We found the cement to be susceptible to low pH and to release a visible cloud of debris upon contact with fluid. Calcium concentration in the solution was elevated at all pH levels. Although we are able to demonstrate these findings in vitro the clinical relevance is unclear. There have been several cases of aseptic meningitis possibly due to intracranial release of components of the cement. Until further studies are done use of the cement in contact with cerebral spinal fluid should be avoided. This cement, or a similar material, would be useful in neurotologic surgery but prior to widespread use further testing should be done to assess safety.
Verrucous carcinoma is a well-differentiated squamous cell carcinoma with minimal cytologic atypia. Characteristically, the surface shows papillary fronds with prominent hyperkeratosis. Its benign appearance makes diagnosis difficult and often delays treatment. This is a review of 52 histologically confirmed cases of verrucous carcinoma of the larynx treated at the Mayo Clinic between 1960 and 1987. The follow-up ranged from 2 to 304 months. The most common primary treatment modality was surgery. Two patients died of laryngeal cancer. In both cases, the recurrence was a high-grade carcinoma histologically distinct from the original verrucous carcinoma. The T stage, clinical stage, and type of surgical excision failed to predict survival. The presence of extensive leukoplakia surrounding the exophytic tumor approached statistical significance (p = .08) in predicting recurrence. Four patients were treated with radiotherapy--in each, to control residual disease. One of these patients developed a local recurrence. None of the irradiated tumors in this series showed anaplastic dedifferentiation, and none of the irradiated patients died of uncontrolled local or regional disease. We conclude that verrucous carcinoma of the larynx should be treated by conservative surgical resection when possible. Radiotherapy can be effectively used for disease that cannot be resected with preservation of laryngeal function. Total laryngectomy should be reserved for recurrent disease or the rare case of anaplastic transformation.
Cervicomedullary compression (CMC) from traumatic, infectious, or congenital processes of the atlanto-axial joint is a known cause of vocal cord immobility. Cervicomedullary compression can also occur from destructive arthritic changes and inflammatory pannus formation at the occipito-atlanto-axial joint in patients with rheumatoid arthritis (RA). We present findings suggesting that CMC in patients with RA is an unrecognized cause of vocal cord immobility. Previously, vocal cord immobility in patients with RA has been assumed to be cricoarytenoid arthritis with joint fixation. We report 3 patients with RA and radiographically demonstrated CMC with vocal cord immobility. One patient had bilateral vocal cord immobility and airway obstruction; 2 patients had unilateral cord paralysis and contralateral paresis without airway compromise. All patients had myelopathy and neck pain in addition to brain stem symptoms. All patients underwent transoral-transpharyngeal decompression of the anterior craniocervical junction with subsequent posterior fusion. These patients demonstrated full return of vocal cord function within 3 months of decompression. We propose that CMC is a cause of vocal cord paralysis in patients with RA that may go unrecognized without appropriate imaging studies of the skull base and physician awareness of symptoms of occipito-atlanto-axial subluxation and/or basilar invagination with brain stem compression. Our results demonstrate that CMC in RA is a potentially reversible cause of vocal cord paralysis.
It has been suggested that leukotrienes C4 (LTC4) and D4 (LTD4) released from upper respiratory mucosa influence mucociliary transport during allergic reactions. We studied the in vitro effects of leukotrienes C4 and D4 on the ciliary beat frequency (CBF) of human adenoid explants over a 5-hour period. Tissue explants were cultured at 35 degrees C in Minimum Essential Medium Eagle (MEM). The CBF was measured using phase contrast microscopy and microphotometry. Measurements of CBF were recorded in medium alone and in medium containing LTC4 or LTD4 at concentrations of 10(-8) and 10(-6) M. LTC4 and LTD4 increased CBF at concentrations of 10(-8) and 10(-6) M with increases of 20.51% +/- 2.69% and 29.84% +/- 4.06%, respectively. To determine the specificity of the LTC4 and LTD4 effects, the ciliated epithelium was treated with the specific leukotriene receptor antagonist LY-171,883 before administration of LTC4 and LTD4. LY-171,883 (10(-6) M) significantly inhibited the ciliostimulatory effects of both leukotrienes. Our findings indicate that LTC4 and LTD4 increase CBF in vitro by activation of the LTD4 receptor.
OBJECTIVE: To determine clinical and surgical factors that affect the recurrence of dermatofibrosarcoma protuberans of the head and neck. DESIGN: Retrospective case series of 32 patients who were seen between 1960 and 1995 with a diagnosis of dermatofibrosarcoma protuberans of the head and neck. Data extracted from patients records included sex, age at diagnosis, tumor site, presence or absence of tumor-free margins, initial and salvage treatment, time to recurrence, and status after last treatment. SETTING: Academic tertiary care referral center. INTERVENTION: Surgical excision and radiation therapy. RESULTS: Univariate Kaplan-Meier analysis for recurrence showed the difference in survival to be statistically significant (P < .05) between patients who had wide (> or = 2 cm) surgical margins vs those who had close (< 2 cm) margins. Univariate Kaplan-Meier analysis for recurrence with or without radiation as the grouping variable showed the difference to be statistically significant (P < .01). Similar analyses with sex, age, tumor site, and size of tumor as the grouping variables were not statistically significant. Multivariate Cox regression analysis was used with sex, age, and close or wide margins as variables. Close margins (< 2 cm) had a statistically significant positive correlation with recurrence (P < .05), while sex and age were not associated with recurrence. CONCLUSION: Surgical margins of at least 2 cm should be used in all cases of dermatofibrosarcoma protuberans of the head and neck to prevent recurrence.
OBJECTIVES: To determine prognostic factors for survival in patients with invasive well-differentiated thyroid carcinoma, specifically examining laryngotracheal invasion as an independent prognostic factor, and to compare types of surgical resection to determine treatment efficacy. DESIGN: Retrospective review of patients with papillary invasive well-differentiated thyroid carcinoma surgically treated over 45 years. SETTING: Academic tertiary care medical center. PATIENTS: A total of 292 patients with invasive well-differentiated thyroid carcinoma were surgically treated between 1940 and 1995. Informed consent was obtained from all patients. Extent and location of tumor invasion were determined. Invasion of larynx and/or trachea occurred in 124 patients (41%). Patterns of invasion and techniques of surgical resection were evaluated. INTERVENTION: Types of surgical resection performed: complete tumor removal (n = 34), "shave" excision (n = 75), and incomplete tumor excision (n = 15). MAIN OUTCOME MEASURES: Cox regression analysis was used to determine significance of prognostic factors for survival; Kaplan-Meier curves were used to evaluate survival. A P value of less than .05 was statistically significant. RESULTS: Patterns of invasion by thyroid carcinoma included direct spread through laryngeal framework into paraglottic space or spread from involved lymph nodes. Laryngotracheal invasion was a significant, independent, prognostic factor for survival (P < .05). Significance was reached when types of resection were compared for all patients (P < .05) as well as for those with laryngotracheal invasion alone (P < .001). CONCLUSIONS: Laryngotracheal invasion was a significant independent prognostic factor for survival (P < .05). When types of surgical resection were compared, the survival rates of patients who underwent shave excision were not different from those of patients who underwent radical tumor resection if gross tumor did not remain (P > .05). Tumors with minimal invasion may be treated by shaving tumor from the aerodigestive tract. Gross intraluminal involvement should be resected completely to prevent complications.
OBJECTIVES: To assess our initial success using the Provox (Atos Medical AB, Horby, Sweden, and Entermad BV, Woerden, the Netherlands) tracheoesophageal speaking valve as the primary prosthesis to rehabilitate patients after total laryngectomy and to compare our success and complication rates with those previously reported. DESIGN: A retrospective analysis of all the patients who had a Provox prosthesis placed from November 1994 to November 1995. PATIENTS AND METHODS: Medical charts were reviewed for success or failure of the prosthesis as determined by the quality of speech and the utility of the device. In addition, complications, whether the patient had a pharyngeal myotomy and/or radiation, and the reasons and timing for replacement were assessed. Twenty-one patients had a Provox prosthesis placed either primarily at the time of their total laryngectomy (n = 8), delayed (n = 5), or as a replacement for another type of prosthesis (n = 8). Follow-up ranged from 2 to 17 months. RESULTS: The initial success rate was 84%, and the long-term success rate was 74%. Of note, 3 patients had substantially improved speech and none were worse when changed from another type of prosthesis. The mean interval to prosthesis change was 166 days. Reasons for failure included infection, radiation fibrosis, manual incoordination, cerebrovascular accident, and combination of total laryngectomy and total glossectomy. The most common complication (in 2 patients) was retraction of the prosthesis into the esophagus that was successfully managed by replacement with a longer device. CONCLUSION: Our early results confirm the effectiveness, longevity, and safety of the Provox prosthesis for speech rehabilitation following total laryngectomy.
BACKGROUND: Laryngeal chondrosarcomas occur infrequently. Their management is often guided by inferences made from the management of sarcomas arising from more commonly afflicted organs. METHOD: A retrospective analysis of patients with laryngeal chondrosarcomas treated at the Mayo Clinic between 1959 and 1992 was performed to assess prognostic factors and outcomes after various treatments. RESULTS: A total of 20 patients received treatment during this time period. All chondrosarcomas were low grade; 19 involved the cricoid cartilage and one arose in the supraglottic larynx. Initial treatment consisted of local excision (often subtotal removal) alone in 12 patients (60%), hemilaryngectomy in 2 (10%), near total laryngectomy in 2 (10%), and total laryngectomy in 4 (20%). Six patients (30%) had local recurrence: five initially had local excision and one had hemilaryngectomy. All local recurrences or tumor progression developed >3 years after initial treatment. Salvage surgery was performed in five of the six patients who had local recurrence, and the other patient was observed. Of the five patients who had salvage surgery, three required another resection because of a second recurrence. CONCLUSIONS: These results suggest that initial conservative subtotal laryngectomy should be explored further because this treatment may provide long-term voice preservation in most patients, and patients who experience a recurrence after local excision often have been given several years of voice preservation.
Fungi represent the etiologic agent in a large number of patients with chronic sinusitis. Despite this, no study has examined the effects of fungi on ciliated epithelium. This study evaluates the effects of cultures and filtrates of Aspergillus fumigatus and Alternaria alternata on ciliary beat frequency (CBF) in vitro. CBF was recorded after exposure to either a control or experimental solution. A statistical comparison of control and experimental values was performed to determine significance at P < 0.05. A statistically significant inhibition of CBF in cultures and filtrates of A fumigatus and A alternata was demonstrated. We conclude that a soluble metabolite produced by clinical isolates of both A fumigatus and A alternata causes inhibition of CBF and may represent one virulence factor involved in the development of fungal sinusitis.
The release of endogenous neurotransmitters plays an important role in the airway mucosal defense system. We studied the in vitro effect of methacholine, a beta-methyl ester of acetylcholine, on the ciliary beat frequency (CBF) of human adenoid explants and its mechanism of action. Tissue explants were cultured at 35 degrees C and covered with 1.0 mL of culture medium: minimum essential Eagle's medium (MEM) containing L-arginine (1.2 x 10(-3) mol/L). Methacholine was added to the cultured tissue at concentrations of 10(-10), 10(-8), and 10(-6) mol/L. The CBF was determined by phase contrast microscopy and microphotometry. Methacholine increased CBF in a dose-dependent manner with a maximum increase of 23.0% +/- 1.8% (p < .001). Atropine (10(-6) mol/L) significantly inhibited the ciliostimulatory effects of methacholine (p < .0007). The role of endogenous prostaglandins in methacholine-induced ciliostimulation was determined by treating specimens with a cyclooxygenase inhibitor (diclofenac sodium). Diclofenac (10(-6) mol/L) significantly inhibited the ciliostimulatory effects of methacholine (p < .0007). To determine if nitric oxide (NO) acts as an intermediary in ciliostimulation by methacholine, endogenous NO production was inhibited by treating specimens with an L-arginine analog, NG-nitro-L-arginine methyl ester (L-NAME), prior to addition of methacholine. L-NAME (10(-6) mol/L) inhibited the effects of methacholine in L-arginine-free MEM (p < .008), and this inhibition was reversed by L-arginine (10(-3) mol/L). To further examine the actions of NO in methacholine-induced ciliostimulation, a cyclic guanosine 3'5'-monophosphate (cGMP) kinase inhibitor (KT-5823) was used, prior to the addition of methacholine. KT-5823 (10(-6) mol/L) significantly inhibited the effects of methacholine (p < .0001). Ciliostimulation by methacholine in human upper airway mucosa involves both prostaglandin and NO second messengers and activation of a cGMP-dependent kinase.
Magnetic resonance angiography is an established radiologic technique which is rapidly becoming useful in imaging the head and neck. Currently, this imaging modality is important in the diagnosis of sigmoid sinus thrombosis caused by otologic disease. Since the introduction of antibiotic therapy, the percentage of deaths attributed to intracranial complications from otitic disease has decreased from 2.5 to approximately 0.25% of documented deaths. Also, the incidence of sinus thrombosis within this group has decreased, but it is still a serious and potentially lethal condition. Sinus thrombosis is suspected clinically when mastoid disease progresses, with picket fence fever pattern, chills, headaches and signs of papilledema. Definitive diagnosis is necessary before surgical treatment. The Queckenstedt test is unreliable, computed tomography is better suited for demonstrating thrombosis of the sagittal sinus rather than the sigmoid sinus, and conventional angiography (although it provides excellent visualization) has the hazard of ionizing radiation and requires vessel puncture and the use of intraarterial contrast agents. We present two cases of thrombosis of the sigmoid sinus as an intracranial otologic complication which were diagnosed definitively with magnetic resonance imaging and magnetic resonance angiography. The combination of magnetic resonance imaging, which showed the thrombosis displaying abnormal signal intensity, and magnetic resonance angiography, which demonstrated the absence of flow in the sinus, was an ideal diagnostic tool. For both patients, treatment consisted of mastoidectomy, sigmoid sinus decompression and antibiotics.
BACKGROUND: It has been recommended that cobalt-60 or 4-MV photons be used when treating glottic cancer with radiation therapy. Underdosing may occur when using higher energy photons, particularly when the anterior commissure is involved. The authors report their experience using higher energy photons (6 MV) for the treatment of glottic cancer. METHODS: Between January 1975 and July 1991, 73 patients with Tis, T1, T2, or T3 glottic tumors underwent radiation therapy with curative intent. Cobalt-60 or 4-MV photons were used to treat the cancers of 30 patients, and 6-MV photons were used to treat 43 patients. Clinical records were reviewed retrospectively to determine patterns of treatment failure, cancer deaths, and local tumor control in the 43 patients receiving treatment with 6-MV photons. Patients were followed until death or for a minimum of two years. RESULTS: Treatment failures were: local recurrence, one patient; local recurrence and distant metastasis, one patient; delayed neck metastasis, two patients; and delayed neck metastasis with distant metastasis, one patient. Three patients who had treatment failure are alive and free of cancer after salvage treatment. Two patients died of neck and distant metastases. The 2-year initial local tumor control rate was 94.8%. CONCLUSIONS: Glottic cancer can be treated successfully with 6-MV photons. Local tumor control is similar to that reported using cobalt-60 or 4-MV photons.
Low-intensity laser stapedotomy has been shown to produce temperature elevations of 3 degrees to 4 degrees C within the cochlea. This study investigates the effect of temperature elevations in this range on cochlear outer hair cell function by use of distortion-product otoacoustic emissions in rabbits. Using esophageal temperature monitoring, we compared 2f1-f2 distortion-product otoacoustic emissions over a range of frequencies (1806 to 8691 Hz) at rabbit normothermia, normothermia plus 3 degrees C, and normothermia after passive cooling. Cochlear temperature was found to exceed changes in esophageal temperature by as much as 1.2 degrees C. We found that a maximum of 3 degrees C elevation in esophageal temperature did not permanently impair outer hair cell function in the rabbit cochlea. Results of this study suggest that moderate changes in cochlear temperature, such as those produced by low-intensity CO2 and holmium-yttrium aluminum garnet lasers, may not produce irreversible thermal damage to the cochlear outer hair cells.
This study investigated the effects of methacholine and terbutaline on the ciliary beat frequency (CBF) of upper airway epithelium. The CBF of cultured human adenoid explants was measured using microphotometry. Methacholine (10(-6) M) and terbutaline (10(-6)M) increased CBF a maximum of 23.0 +/- 1.8% (P < 0.001) and 16.5 +/- 2.3% (P < 0.001). Inhibition of endogenous nitric oxide (NO) production by nitro-L-arginine methyl ester (L-NAME) (10(-6) M) abolished the effects of methacholine in L-arginine-free medium (P < 0.008). This inhibition was reversed by addition of L-arginine. There was no inhibition of terbutaline-induced ciliostimulation by L-NAME (P < 0.5). KT-5823 (10(-6)M), a guanosine 3',5'-cyclic monophosphate (cGMP) kinase inhibitor, significantly inhibited the effects of methacholine (P < 0.0001), but not terbutaline (P > 0.15). H-89 (10(-6) M), a cAMP kinase inhibitor, significantly inhibited terbutaline-induced ciliostimulation (P < 0.0001), but not methacholine-induced ciliostimulation (P > 0.05). Diclofenac (10(-6) M), a cyclooxygenase inhibitor, significantly inhibited the effects of methacholine (P < 0.0007) but had no effect on terbutaline-induced ciliostimulation (P > 0.05). These findings suggest that the CBF of upper airway epithelium is modulated through at least two distinct pathways. The beta 2-adrenoceptor produces ciliary stimulation by a pathway involving increased intracellular cAMP levels, while the muscarinic receptor increases CBF by a mechanism involving production of prostaglandins, NO, and cGMP.