Value of recurrent laryngeal nerve monitoring in the operative strategy during total thyroidectomy and parathyroidectomy.

OBJECTIVE: The purpose of this study was to assess the role of recurrent laryngeal nerve (RLN) monitoring in the operative strategy during total thyroidectomy and parathyroidectomy. Due to the risk of serious respiratory complications of bilateral recurrent nerve paralysis, two-stage surgery may be considered in the case on negative stimulation of the first side. PATIENTS AND METHODS: This prospective study was conducted in 100 consecutive patients between May 2007 and March 2011. Translaryngeal monitoring was performed. When stimulation of the RLN on the first side dissected was negative, dissection of the other side was deferred to avoid the risk of bilateral RLN paralysis. RESULTS: The main surgical indications were thyroid carcinoma (34%), Graves' disease (27%), multinodular goitre (27%) and parathyroid hyperplasia (9%) with seven cases of redo surgery. Four RLN identified on the first side gave a negative response to stimulation and surgery to the other side was therefore deferred. Transient unilateral RLN paralysis was observed in these four patients and two cases of RLN paralysis were observed among patients with positive RLN stimulation. Among the 96 contralateral RLNs tested, two were not visualized (one case of transient RLN paralysis, one case of permanent RLN paralysis), two gave a negative response to stimulation (two cases of permanent RLN paralysis) and 92 gave a positive response to stimulation (nine cases of transient RLN paralysis, including two cases associated with transient paralysis of the first side, and one case of permanent RLN paralysis). The incidence of RLN paralysis by nerve was 9.6% for transient RLN paralysis and 2% for permanent (unilateral) RLN paralysis. CONCLUSION: When bilateral RLN dissection is planned, RLN monitoring is particularly useful to limit the risk of bilateral RLN paralysis. Two-stage thyroidectomy, following functional recovery of the damaged RLN, can therefore be proposed. The risk of bilateral RLN paralysis was avoided in four patients, while transient bilateral RLN paralysis was observed in two patients despite positive stimulation.

Myoblast transfer therapy: is there any light at the end of the tunnel?

Myoblast transfer therapy (MTT) was proposed in the 70's as a potential treatment for muscular dystrophies, based upon the early results obtained in mdx mice: dystrophin expression was restored in this model by intramuscular injections of normal myoblasts. These results were quickly followed by clinical trials for patients suffering from Duchenne Muscular Dystrophy (DMD) in the early 90's, based mainly upon intramuscular injections of allogenic myoblasts. The clinical benefits obtained from these trials were minimal, if any, and research programs concentrated then on the various pitfalls that hampered these clinical trials, leading to numerous failures. Several causes for these failures were identified in mouse models, including a massive cell death of myoblasts following their injection, adverse events involving the immune system and requiring immunosuppression and the adverse events linked to it, as well as a poor dispersion of the injected cells following their injection. It should be noted that these studies were conducted in mouse models, not taking into account the fundamental differences between mice and men. One of these differences concerns the regulation of proliferation, which is strictly limited by proliferative senescence in humans. Although this list is certainly not exhaustive, new therapeutic venues were then explored, such as the use of stem cells with myogenic potential, which have been described in various populations, including bone marrow, circulating blood or muscle itself. These stem cells presented the main advantage to be available and not exhausted by the numerous cycles of degeneration/regeneration which characterize muscle dystrophies. However, the different stem candidates have shown their limits in terms of efficiency to participate to the regeneration of the host. Another issue was raised by clinical trials involving the injection of autologous myoblasts in infacted hearts, which showed that limited targets could be aimed with autologous myoblasts, as long as enough spared muscle was available. This resulted in a clinical trial for the pharyngeal muscles of patients suffering from Oculo-Pharyngeal Muscular Dystrophy (OPMD). The results of this trial will not be available before 2 years, and a similar procedure is being studied for Fascio-Scapulo-Humeral muscular Dystrophy (FSHD). Concerning muscular dystrophies which leave very few muscles spared, such as DMD, other solutions must be found, which could include exon-skipping for the eligible patients, or even cell therapy using stem cells if some cell candidates with enough efficiency can be found. Recent results concerning mesoangioblasts or circulating AC133+ cells raise some reasonable hope, but still need further confirmations, since we have learned from the past to be cautious concerning a transfer of results from mice to humans.

Defective satellite cells in congenital myotonic dystrophy.

In this study we have developed an in vitro cell culture system which displays the majority of the defects previously described for congenital myotonic dystrophy (CDM) muscle in vivo. Human satellite cells were isolated from the quadriceps muscles of three CDM fetuses with different clinical severity. By Southern blot analysis all three cultures were found to have approximately 2300 CTG repeats. This CTG expansion was found to progressively increase in size during the proliferative life span, confirming an instability of this triplet in skeletal muscle cells. The CDM myoblasts and myotubes also showed abnormal retention of mutant RNA in nuclear foci, as well as modifications in their myogenic program. The proliferative capacity of the CDM myoblasts was reduced and a delay in fusion, differentiation and maturation was observed in the CDM cultures compared with unaffected myoblast cultures. The clinical severity and delayed maturation observed in the CDM fetuses were closely reflected by the phenotypic modifications observed in vitro. Since the culture conditions were the same, this suggests that the defects we have described are intrinsic to the program expressed by the myoblasts in the absence of any trophic factors. Altogether, our results demonstrate that satellite cells are defective in CDM and are probably implicated in the delay in maturation and muscle atrophy that has been described previously in CDM fetuses.

Use of a coincidence gamma camera to detect primary tumor with 18fluoro-2-deoxy-glucose in cervical lymph node metastases from an unknown origin.

This study was performed to evaluate the ability of a dual-head gamma camera with 18fluoro-2-deoxy-glucose coincidence detection emission tomography (FDG-CDET) to detect primary tumors in patients with cervical lymph node metastases of head and neck squamous cell carcinoma from an unknown origin. From 60 patients with untreated head and neck squamous cell carcinoma, we selected 4 in whom no evidence of the primary's origin was found by the conventional methods used for the evaluation of head and neck tumors. In addition to the panendoscopy, chest radiography, a computed tomography (CT) scan, and FDG-CDET were performed. Both FDG-CDET and the CT scan located cervical lymph node metastases. In addition, FDG-CDET located the primary tumor in 3 of the 4 patients, and the tumors were confirmed with histopathologic findings. In contrast, the CT scan detected the primary tumor in none of them. FDG tomography performed on a coincidence gamma camera appears to be a successful new tool in detecting occult primary tumors in head and neck carcinoma, and is useful in guiding endoscopic biopsies. It has, further, the important potential ability to detect distant metastases on whole body images.

Conservative surgery in T3-T4 pharyngolaryngeal squamous cell carcinoma: an alternative to radiation therapy and to total laryngectomy for good responders to induction chemotherapy.

OBJECTIVE: To evaluate the possibility of preservation of the larynx after neoadjuvant chemotherapy by performing a conservative surgery instead of total laryngectomy initially planned, in patients with previously untreated laryngeal and piriform sinus squamous cell carcinoma (SCC). STUDY DESIGN: Retrospective study. METHODS: A total of 115 patients treated at Tenon Hospital with induction chemotherapy from 1985 to 1995, all with initial indication of radical surgery, were available for the study. The clinical tumor response was evaluated after three cycles of chemotherapy. According to this response, to preserve laryngeal functions, some patients had a modification of the treatment initially planned: radiation therapy essentially for complete responders, and conservative surgery for some partial responders. RESULTS: Of 69 patients with laryngeal cancer, 14 were treated by partial laryngectomy and 19 by radiation therapy; of 46 patients with piriform sinus cancer, 8 were treated by partial surgery and 12 by radiation therapy; the other patients were treated as was initially planned (total laryngectomy with partial pharyngectomy). Overall survival rates, estimated by the Kaplan-Meier method, were not statistically different between the three treatment groups. The laryngeal functions were preserved in 54% of the patients who were alive at 3 years. CONCLUSION: This report is a retrospective study, but these results suggest the possibility of using conservative surgery, instead of initially planned total laryngectomy, for good responders to induction chemotherapy with a small residual tumor.

Myosin heavy chain expression in human laryngeal muscle fibers. A biochemical study.

Since the intrinsic laryngeal muscles in humans are involved in specialized functions, one may suppose that this would be associated with the expression of specific myosin heavy chain (MHC) isoforms, as has been reported for the rat, dog, and rabbit. In order to determine which MHCs are expressed in the human laryngeal muscles, biochemical analysis using sodium dodecyl sulfate-polyacrylamide gel electrophoresis was performed. Thyroarytenoid and posterior cricoarytenoid muscles were obtained from a 7-month-old infant and 4 adults. In the adult human laryngeal muscles, 3 bands were resolved identical to those previously described in the human limb muscles (I, IIA, and IIB MHCs). In contrast, muscles from the infant also expressed fetal MHC and a novel MHC not observed in other human skeletal muscles. This novel band migrated at the same level as the laryngeal MHC previously described in the rat. Since these 2 isoforms disappear in the adult, the persistence in the infant could be correlated with the immature development of laryngeal functions and, in particular, phonation.

p53 gene status as a predictor of tumor response to induction chemotherapy of patients with locoregionally advanced squamous cell carcinomas of the head and neck.

PURPOSE: To determine whether p53 gene status predicts tumor responses to platinum- and fluorouracil-based induction chemotherapy in locoregionally advanced squamous cell carcinomas of the head and neck. PATIENTS AND METHODS: Tumor responses of 105 patients were measured at the primary tumor site. Objective response and major response were defined by a 50% and 80% reduction in tumor size, respectively. All coding parts of p53 gene were directly sequenced. p53 expression in tumor cells was determined by immunohistochemistry. Human papillomavirus infection was detected by polymerase chain reaction. Odd ratios were adjusted by stepwise logistic regression analysis. RESULTS: p53 mutations, p53 expression, and tumor stage were sufficient to explain the variation in tumor responses to chemotherapy in multivariate models. p53 mutation was the only variable to significantly predict objective response (odds ratio, 0. 23; 95% confidence interval, 0.10 to 0.57; P =.002) and was the strongest predictor of major response (odds ratio, 0.29; 95% confidence interval, 0.11 to 0.74; P =.006). p53 expression (odds ratio, 0.39; 95% confidence interval, 0.16 to 0.98) and tumor stage (odds ratio, 0.31; 95% confidence interval, 0.10 to 0.96) also predicted major response. Specific mutations (contact mutations) accounted for much of the reduction in the risk of major response associated with overall mutations. In complementary analyses, p53 expression was weakly predictive of major response in the subgroup with wild-type p53, and p53 mutations also predicted histologic response. CONCLUSION: p53 gene mutations are strongly associated with a poor risk of both objective and major responses to chemotherapy. Contact mutations are associated with the lowest risk of major response to chemotherapy.

Osteoradionecrosis of the hyoid bone: a report of 3 cases.

PURPOSE: Osteonecrosis of the hyoid bone is an uncommon disease that has only been described occasionally in the literature. MATERIALS AND METHODS: We report 3 cases of osteonecrosis of the hyoid bone after radiation therapy for carcinoma at various sites in the head and neck region. RESULTS: Imaging computed tomography (CT) scans were performed for all 3 cases and did aid in the diagnosis. In 1 case, a 201thallium scintigraphy and a bone scan (99mtechnetium-diphosphonate) were performed and this confirmed the diagnosis of osteoradionecrosis. CONCLUSION: Osteoradionecrosis of the hyoid bone may be misdiagnosed as recurrent neoplasm. Although recurrent or persistent neoplastic disease must initially be ruled out, it is subsequently important to correctly identify osteonecrosis of the hyoid bone, because its surgical treatment is simple and the prognosis is good.

Swallowing difficulties for cerebellar stroke may recover beyond three years.

Swallowing disorders after stroke or skull base surgery can be life threatening. Although late recovery can occur, it remains poorly documented. We report a case of a 54-year-old woman with dysphagia resulting from a cerebellar stroke with hemorrhage that was evacuated through craniotomy. Swallowing difficulties were assessed by a videoendoscopic swallowing study. She presented with disruption of swallow initiation and impairment of the pharyngeal stage, resulting in hypopharyngeal stasis and penetration with aspiration. Supportive swallowing therapy was conducted with careful reeducation to assist initiation of the pharyngeal stage as well as development of compensatory postural technique. Initial improvement was very slow but became rapidly progressive from the 31st month after the stroke. By the 34th month, oral feeding was possible without aspiration. This case demonstrates that improvement in swallowing function can be expected even 3 years after stroke or skull base surgery. Determination of predictive factors for late functional recovery is of great importance and should be the focus of further investigation.

Comparison of perinatal and adult multi-innervation in human laryngeal muscle fibers.

The innervation of human laryngeal myofibers appears distinct from that of skeletal myofibers, because some of them exhibit multiple neuromuscular junctions. We attempted to understand the significance of the multi-innervation phenomenon by comparing intrinsic laryngeal muscles obtained from autopsies of a fetus, a stillbirth, and a 7-month-old infant to muscles from adults. In longitudinal sections (40 to 60 microm thick) the cholinesterase sites and the nerve terminals were stained simultaneously for light microscopy. Multi-innervation reached no more than 23% at 7 months, and this percentage decreased notably with age. Until 7 months, end plates were innervated either by single or by multiple axons (unineuronal and polyneuronal innervation), whereas in adults, the pattern was exclusively unineuronal. Moreover, the structure of neuromuscular junctions in the young was limited to 1 spot of acetylcholinesterase, while in adults the end plate zones increased in size and complex axon terminals were observed. These observations are consistent with a delayed maturation of human laryngeal innervation compared to that of skeletal muscles.

Swallowing disorders in paralysis of the lower cranial nerves: a functional analysis.

Deficits of the lower cranial nerves (nerves IX, X, XI, and XII) occurring after treatment of skull base tumors may cause disabling swallowing disorders. To assess the mechanisms of swallowing disorders involved in such cases, we performed functional examinations: a videoendoscopic swallowing study and simultaneous manometry and videofluoroscopy in 7 patients. This study shows that the main mechanism of the swallowing disorders was a disturbance of the pharyngeal stage, including a decrease of pharyngeal propulsion, reduced laryngeal closure, and cricopharyngeal dysfunction, which led to aspiration. Decreased pharyngeal propulsion was found in 6 patients, with a very high correlation between fiberoscopy and simultaneous manometry-fluoroscopy. The responsibility of the upper esophageal sphincter in swallowing disorders was more difficult to assess. The role of the upper esophageal sphincter and pharyngeal propulsion in the onset of the problem is discussed in regard to the cricopharyngeal myotomy.

The "sign of the rising tide" during swallowing fiberoscopy: a specific manifestation of Zenker's diverticulum.

Pooling of secretions in the hypopharynx is a common sign of an impaired upper esophageal sphincter. Until now, no specific manifestation, observed by flexible laryngoscopy, of Zenker's diverticulum has been reported. Direct visualization of the diverticulum can be missed during flexible laryngoscopic examination. In this series of 12 patients with hypopharyngeal diverticulum, we have described a manifestation of Zenker's diverticulum obtained on videofiberoscopy during cream swallowing. We have called it the "sign of the rising tide" because it describes the backup of cream visible in the hypopharynx as a wave after its complete disappearance. Barium swallow study is necessary to confirm the presumptive diagnosis. This relevant manifestation seems to be specific for Zenker's diverticulum, since it is not observed in other upper esophageal sphincter disorders, and it disappears when surgical treatment is successful.

Role of videoendoscopy in assessment of pharyngeal function in oropharyngeal dysphagia: comparison with videofluoroscopy and manometry.

OBJECTIVE: The purpose of the current report is to evaluate the ability of videoendoscopic swallowing study in assessing pharyngeal propulsion and aspiration episodes when compared with videofluoroscopy and manometry. STUDY DESIGN: Prospective study. METHODS: Thirty-four patients with oropharyngeal dysphagia underwent videoendoscopy of swallowing to assess pharyngeal propulsion as pathologic or nonpathologic, and aspiration. These features were compared with those found on manometry and videofluoroscopy, which were considered as the reference examinations. Sensitivity, specificity, and positive and negative predictive values of videoendoscopy were estimated, with their 95% confidence intervals. RESULTS: A total agreement between videoendoscopy and videofluoroscopy was found in 76.4% of cases for pharyngeal propulsion and in 82.3% for aspiration. This rate for pharyngeal propulsion reached 82.3% between videoendoscopy and manometry. Moreover, in 24 cases (70.5%) in which videofluoroscopy and manometry agreed for pharyngeal propulsion, 22 were assessed similarly through fiberoscopy. When using fluoroscopy and manometry as reference examinations, videoendoscopy detected nearly 90% (95% confidence interval [CI] = 0.80, 1.0) of impaired pharyngeal propulsion. Concerning aspiration, 70% (95% CI = 0.54, 0.85) of events detected by videoendoscopy were also observed on videofluoroscopy. Sensitivity, specificity, and positive and negative predictive values of videoendoscopy reached a higher rate (90% to 92.8%) when agreement was found between fluoroscopy and manometry. CONCLUSIONS: Videoendoscopy is an examination that can be used to detect inexpensively pharyngeal propulsion disorders and aspiration episodes.

Innervation of adult human laryngeal muscle fibers.

The innervation of laryngeal muscle fibers was appraised in adult humans. Sixteen intrinsic laryngeal muscles were dissected during the autopsy of 4 adults (41-71 years old). Longitudinal serial frozen sections, 60 microm thick, of the whole muscles were double-stained for cholinesterase activity and axonal visualization. About 945 endplates per muscle were analysed using light microscopy. The neuromuscular junctions were always scattered throughout the whole muscles. Most of the muscle fibers showed a single neuromuscular junction, but multi-innervated fibers were found in all of the muscles. Their number was highest in interarytenoid muscles (21% of all the fibers). The distance between multiple neuromuscular junctions was most frequently less than 150 microm. Two neuromuscular junctions were frequently displayed, opposite one another, particularly in thyroarytenoid muscles, and this unusual feature seems specific for laryngeal muscles. The innervation of all of the muscle fibers was exclusively found to be unineuronal, with multi-innervated fibers being innervated by a single axon. Distal axonal degeneration occurred with aging, resulting in a loss in the number of multi-innervated muscle fibers.

Human papillomavirus in head and neck squamous cell carcinomas in nonsmokers.

OBJECTIVE: To establish relationships between smoking status and human papillomavirus in head and neck squamous cell carcinomas. DESIGN: Human papillomavirus was detected in paraffin-embedded samples using E6-directed consensus primers and type-specific oligonucleotide probes. Patients were classified as smokers and nonsmokers. Alcohol use was also recorded. Data were analyzed by means of the Fisher exact test. Sequence analysis of exons 5 to 8 of the p53 gene was performed in tumor samples from nonsmokers. SETTING: Academic medical center in Paris, France. PATIENTS: One hundred eighty-seven consecutive patients with head and neck squamous cell carcinoma. RESULTS: The overall prevalence of human papillomaviral infection was 10.7%. Human papillomavirus occurred more frequently (P = .02) in oropharyngeal squamous cell carcinoma (18.6%) than in other locations (6.1%). There were 10 nonsmokers (5%). The 50% incidence of human papillomavirus in nonsmokers (95% confidence interval, 19%-81%) differed significantly from the 8.5% incidence in smokers (95% confidence interval, 5%-14%; P = .003). No occupational risk factor was recorded in nonsmokers. None of these patients had p53 gene mutations in cancer cells. CONCLUSION: These findings suggest that human papillomavirus may play a role in head and neck squamous cell carcinomas in nonsmokers.

Role of pharyngeal propulsion as an indicator for upper esophageal sphincter myotomy.

Thirty-eight patients with swallowing disorders underwent cricopharyngeal myotomy. The causes of the disorders were muscular in 12 cases, neurologic in 12, cricopharyngeal achalasia in 7, and unknown in 7. Surgery succeeded in 21 patients, gave a partial improvement in 4, and failed in 13. The quality of residual pharyngeal propulsion on clinical, manometric, and radiologic assessment appeared to be a more important predictor of surgical outcome than upper esophageal sphincter relaxation and the major factor in establishing the indications for cricopharyngeal myotomy. Achalasias in the elderly and oculopharyngeal muscular dystrophies had the most favorable outcome.

Swallowing disorders in muscular diseases: functional assessment and indications of cricopharyngeal myotomy.

Thirty-four patients with an identified muscular disease were referred to our department for assessment and treatment of swallowing difficulties. Their ages ranged from 16 to 91 years (mean 59). The diagnoses were oculopharyngeal dystrophy in 17 patients, Steinert myotonic dystrophy in 6, mitochondrial myopathies in 4, polymyositis in 3, and other types in 4 patients. The main consequences of the dysphagia were weight loss (12 patients), pulmonary infections (15 patients), modified food consistency (18 patients) and non-oral feeding (3 patients). Several techniques were used to assess the different stages of deglutition: physical examination during swallowing, videofluoroscopy, pharyngoesophageal manometry, videofibroscopy of the pharynx during swallowing. Major pathological features found in the pharynx were decreased pharynx peristaltis and impaired UES relaxation. Cricopharyngeal myotomy was performed in 11 myopathic patients (median follow-up 24.9 months), while it was unnecessary, refused or contraindicated in the other patients. The procedure was successful in 8 patients whose dysphagia was dramatically improved, and failed in 3 patients. Pharyngeal perstaltis was severely impaired only in the 3 failures and was partly preserved in the improved cases. We conclude that pharyngeal function is the major prognostic factor. Cricopharyngeal myotomy is an effective treatment in those cases where cricopharyngeal dysfunction is a predominant problem or where pharyngeal peristaltis is partly impaired, since the procedure removes one obstacle. It is contraindicated when pharynx propulsion is severely impaired.

Postlaryngectomy voice restoration. A prospective study in 83 patients.

From July 1985 until May 1990, 83 patients underwent a total laryngectomy. We prospectively studied voice restoration in 81 of them (two died postoperatively). Esophageal voice was used by 19 patients; a tracheoesophageal procedure (myomucosal shunt, primary or secondary puncture with Blom-Singer prosthesis) by 41; and 21 patients had no voice restoration. Results were assessed according to voice quality and usage. Tracheoesophageal speech had a success rate of 73% (good voice, daily use) after 1 month, while esophageal voice proved to have only a 5% success rate. Thirty patients (37%), however, remained without a substitute voice. The reasons for their exclusion are presented; they include a high rate of refusal.