Steven M. Zeitels

Outcomes of atypical symptoms attributed to gastroesophageal reflux treated by laparoscopic fundoplication

BACKGROUND The introduction of laparoscopic fundoplication (LF) has lowered the threshold for operation in patients with symptoms attributed to gastroesophageal reflux. We sought to determine whether the outcomes in patients referred for atypical symptoms (pulmonary, pharyngolaryngeal, and pain syndromes) were as good as those referred for correction of heartburn and regurgitation (typical symptoms). METHODS Thirty-five of 150 consecutive patients undergoing LF with a minimum of 12 months of follow-up were referred primarily for correction of atypical symptoms. A standard preoperative evaluation included endoscopy, manometry, upper gastrointestinal contrast radiography, and 24-hour pH probe testing (33 of 35 patients with atypical symptoms). Patients completed a symptom questionnaire administered by a study nurse before the operation and 3 and 12 months after the operation. Symptoms were scored from 0 to 10. RESULTS Heartburn was relieved by LF in 93% of patients, whereas only 56% of patients had relief of atypical symptoms. Furthermore, the degree of improvement in typical symptoms was greater than that seen for atypical symptoms as measured by the 0 to 10-symptom rating score (improvement in typical symptoms = 6.2 vs improvement in atypical symptoms = 4.4 [p = 0.01]). The response rate for laryngeal, pulmonary, and epigastric/chest pain symptoms was 78%, 58%, and 48%, respectively. Analysis of factors associated with relief of atypical symptoms revealed that response to a preoperative trial of omeprazole or H2-blockers was significantly associated with successful surgical outcome (p = 0.03). Six of seven patients with laryngeal symptoms who had acid reflux above the cricopharyngeal level shown by dual-probe pH testing had relief of the symptoms after LF. Manometric findings (amplitude of esophageal body contractions, propagation of contractions, and lower esophageal sphincter resting pressure) neither predicted nor correlated with relief of atypical symptoms after the operation. CONCLUSIONS Relief of atypical symptoms attributed to gastroesophageal reflux by LF is less satisfactory and more difficult to predict than relief of heartburn and regurgitation. The only useful preoperative predictors of relief of atypical symptoms in this study were the response to pharmacologic acid suppression and dual-probe pH testing (only in patients with laryngeal symptoms).

Premalignant epithelium and microinvasive cancer of the vocal fold: The evolution of phonomicrosurgical management

Phonomicrosurgical treatment of premalignant vocal fold epithelium and microinvasive cancer combines principles of surgical oncology with advanced laryngoscopic microsurgical‐techniques. This treatment is guided by mucosal‐wave theory of voice production and strives not only to cure the disease but also to achieve optimal vocal function.

Incorporation of a matrix metalloproteinase-sensitive substrate into self-assembling peptides - a model for biofunctional scaffolds.

Controlling and guiding cell behavior requires scaffolding materials capable of programming the three-dimensional (3-D) extracellular environment. In this study, we devised a new self-assembling peptide template for synthesizing nanofibrous hydrogels containing cell-responsive ligands. In particular, the insertion of a matrix metalloproteinase-2 (MMP-2) labile hexapeptide into the self-assembling building blocks of arginine-alanine-aspartate-alanine (RADA) was investigated. A series of peptides, varied by the position of the MMP-2 hexapeptide substrate and the length of RADA blocks, were prepared by parallel synthesis. Their self-assembling capabilities were characterized and compared by circular dichroism spectroscopy and dynamical mechanical analysis. Among all the different insertion patterns, the sequence comprising a centrically positioned MMP-2 substrate was flanked with three RADA units on each side self-assembled into a hydrogel matrix, with mechanical properties and nanofiber morphology comparable to the native material built with (RADA)(4) alone. Exposure of the new gel to MMP-2 resulted in peptide cleavage, as confirmed by mass spectroscopy, and a decrease in surface hardness, as detected by nanoindentor, indicating that the enzyme mediated degradation was localized to the gel surface. The new design can be used for introducing biological functions into self-assembling peptides to create scaffolding materials with potential applications in areas such as tissue engineering and regenerative medicine.

Early versus late injection medialization for unilateral vocal cord paralysis

To evaluate whether the timing of early (≤6 months from time of nerve injury) vs. late (>6 months) injection medialization laryngoplasty impacts the need for subsequent open‐neck reconstruction to restore vocal function in patients with unilateral vocal cord paralysis.

Endoscopic treatment of supraglottic and hypopharynx cancer

Transoral excision of supraglottic and hypopharynx cancer as a single modality is effective when lesions are selected for small size and endoscopic accessibility. Excisional biopsy with clear margins of larger supraglottic tumors in combination with postoperative radiotherapy provides an excellent treatment alternative for selected lesions in patients who are not candidates for open surgery. In this preliminary report, 45 cases using this minimally invasive approach are reviewed outlining oncologic rationale and functional advantages.

Larynx preservation using induction chemotherapy plus radiation therapy as an alternative to laryngectomy in advanced head and neck cancer. A long-term follow-up report

Since 1977, we have used induction chemotherapy (CT) plus radiation therapy (RT) with curative intent in 35 advanced head and neck cancer (Ca) patients who otherwise would have required total laryngectomy. Fourteen patients had advanced Ca of the larynx or supraglottic larynx (SGL); 21 patients had Ca of the hypopharynx. In six. patients the Ca was Stage III; in 26 patients it was Stage IV. Three patients had Stage II disease—2 with cancer of the pyriform sinus and one patient with Stage II SGL Ca who refused surgery. Chemotherapy consisted of platinum (P) + bleomycin in 18 patients until 1982, then P + fluorouracil in the next 17 patients. Total response rate was 77%—complete (CR) in 26% and partial (PR) in 51%. There were two toxic deaths. Surgery was limited to tracheostomy in 4 patients prior to CT and to radical neck dissection after CT in 4 others. Two patients required salvage laryngectomy at 11 and 31 months, respectively. One patient underwent partial laryngectomy with voice preservation. Thirty-two patients were evaluable for overall response after RT. Final disease-free status was achieved in 20/34. One long-term survivor was lost to follow-up (44 months) and 8 patients remained alive at 13+ to 109+ months. Median failure-free survival for all patients was no less than 24 months. Not counting 4 early deaths free of disease, 2-year local control using only chemotherapy plus radiation was 52% (16:31). Overall, 33 of 35 patients retained their voices. Sixteen patients (46%) have survived 2 years or longer. Survival of patients who achieved CR after induction chemotherapy was 48 months versus 14 months for those with less than a CR (p = 0.001). Patients with a hypopharyngeal primary had only a 33% 2-year local control rate with chemotherapy and radiation and a median survival of only 12 months versus 77% control and a minimum 39-month survival for those whose tumor arose in the larynx (p = 0.009). Induction chemotherapy plus radiation therapy is an effective strategy which can produce a high rate of larynx preservation, local control, and long-term survival in patients with advanced cancer of the larynx. Patients with hypopharyngeal primaries have a lesser rate of long-term survival and local control, despite similar overall response rates.

Quantitative and Comparative Studies of the Vocal Fold Extracellular Matrix II: Collagen

Objectives: This study examines the collagen content and turnover in the midmembranous vocal fold laminae propriae (LPs) of humans, dogs, pigs, and ferrets. Methods: The LP collagen levels were assessed by quantifying tissue hydroxyproline. Quantitative histology allowed evaluation of the collagen content in specific LP regions. Several collagen types and Two markers of collagen turnover were examined immunohistochemically. Results: Collagen made up 43.4% ± 2.6% of human LP total protein (TP), with men having approximately 30% higher collagen content than women (p > .024). The collagen levels in pigs (52.6% ± 1.9% of TP) and ferrets (29.8% ± 3.7% of TP), but not that in dogs (45.3% ± 1.2% of TP), varied significantly from that in humans (pigs, p > .016; ferrets, p > .011). Quantitative histology indicated marked interspecies differences in total collagen distribution. Collagen types I, III, and IV were detected in the LP, and spatially complex staining patterns were observed for the Two markers of collagen turnover studied. Conclusions: The collagen content of the human LP is approximately 60% to 70% of that of human dermis. Although canine LP collagen levels are most similar to those of humans, quantitative histology indicates that the collagen distribution of the human LP is best matched by the porcine LP. Collagen types I and III seem to be the dominant LP collagens. Spatial variations in collagen turnover appear to exist that may contribute to normal LP physiology.

Quantitative and comparative studies of the vocal fold extracellular matrix. I: Elastic fibers and hyaluronic acid.

Objectives: This study examines the elastic fiber and hyaluronic acid (HA) content of the midmembranous vocal fold laminae propriae (LPs) of humans, dogs, pigs, and ferrets. Methods: Lamina propria elastin was quantified by measuring the amino acid desmosine, and HA was measured by an enzyme-linked immunosorbent assay-based technique. Quantitative histology was used to evaluate elastin and HA levels in specific LP regions. The distributions of fibrillin-1, a primary microfibrillar component of elastic fibers, and of tropoelastin, an indicator of elastin synthesis, were immunohistochemically analyzed. Results: Elastin and HA constituted 8.5% ± 2.1% and 0.82% ± 0.11% of human LP, respectively, relative to tissue total protein. Although the mean LP desmosine levels were similar across species, the mean HA levels in canine (p < 3.1 × 10−5), porcine (p < 1.5 × 10−5), and ferret (p < 6.6 × 10−4) LPs were 3 to 4 times higher than that in humans. Marked interspecies differences in elastin, fibrillin-1, tropoelastin, and HA distributions were observed histologically. Conclusions: The elastin content of the human LP is roughly twice that of the dermis, whereas the HA content of the human LP is similar to that of the dermis. Although all species had similar levels of desmosine, histologic evaluation indicates that the porcine elastin distribution is most similar to that of the human LP. Fibrillin-1 staining suggests that stress in the human LP may be particularly high in the superior superficial layer, and tropoelastin staining indicates that the rate of LP elastin turnover may vary spatially.

Ambulatory monitoring of disordered voices

Objectives: Recently developed systems for ambulatory monitoring of voice use employ miniature accelerometers placed at the base of the anterior neck to sense phonation. As it is hoped that such systems will help improve the clinical assessment and management of voice disorders, this study was undertaken to determine the impact of dysphonia severity on the accuracy of accelerometer-based estimates of vocal function. Methods: Simultaneous recordings were made of oral acoustic (microphone) and neck skin acceleration signals for 6 normal speakers and 18 patients with voice disorders (mild to severe dysphonia) as they performed several speech tasks. Measures of phonation time, fundamental frequency, and sound pressure level were extracted from the Two types of signals and compared. Results: It was generally demonstrated that accelerometer-based measures closely approximated corresponding measurements obtained from a microphone signal across all levels of dysphonia severity. Furthermore, there was evidence that in some cases the accelerometer may actually represent a more robust approach for estimating phonation parameters in disordered voices. Conclusions: The results generally support the recent application of accelerometers as phonation sensors in ambulatory voice monitoring systems that can be used in the clinical assessment and management of voice disorders.

Phonomicrosurgery in singers and performing artists: treatment outcomes, management theories, and future directions.

Phonomicrosurgery in performing artists has historically been approached with great trepidation, and vocal outcome data are sparse. The vocal liability of surgically disturbing the superficial lamina propria (SLP) and epithelium must be balanced with the inherent detrimental vocal effect of the lesion(s). A prospective investigation was performed on 185 performing artists who underwent phonomicrosurgical resection of 365 lesions: 201 nodules, 71 polyps, 66 varices and ectasias, 13 cysts, 8 keratotic lesions. 2 granulomas, 2 Reinkes edema, and 2 papillomas. Nearly all patients with SLP lesions reported improvement in their postsurgical vocal function. This subjective result was supported by objective acoustic and aerodynamic measures. All postsurgical objective vocal function measures fell within normal limits, including a few that displayed presurgical abnormalities. However, given the relative insensitivity of standard objective measures to assess higher-level vocal performance-related factors, it is even more noteworthy that 8 of 24 objective measures displayed statistically significant postsurgical improvements in vocal function. Such changes in objective measures mostly reflect overall enhancement in the efficiency of voice production. Phonomicrosurgical resection of vocal fold lesions in performing artists is enjoying an expanding role because of a variety of improvements in diagnostic assessment, surgical instrumentation and techniques, and specialized rehabilitation. Most of these lesions are the result of phonotrauma and arise within the SLP. Successful management depends on prudent patient selection and counseling, ultraprecise technique, and vigorous vocal rehabilitation. Furthermore, an understanding of the vocal function and dysfunction of this high-performance population provides all otolaryngologists who manage laryngeal problems with valuable information that they can extrapolate for use in their practices.