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Vulnerability of the recurrent laryngeal nerve in the anterior approach to the lower cervical spine.

STUDY DESIGN: To perform anatomic dissections and measurements of the recurrent laryngeal nerve between the inferior thyroid artery and superior border of the clavicle (mid-portion) on both sides. OBJECTIVES: To determine quantitatively the differences in course and location between the recurrent laryngeal nerves on both sides and to relate this to the vulnerability of the recurrent laryngeal nerve during an anterior approach to the lower cervical spine. SUMMARY OF BACKGROUND DATA: The midportion of the recurrent laryngeal nerve is usually encountered in the anterior approach to the lower cervical spine, especially on the right side. No quantitative regional anatomy describing the course and location of the mid-portion of the recurrent laryngeal nerve is available in the literature. METHODS: Fifteen adult cadavers were used for dissections of the recurrent laryngeal nerve. The length of the recurrent laryngeal nerve between the superior border of the clavicle and the inferior thyroid artery, and the angle of the recurrent laryngeal nerve with respect to sagittal plane, were measured bilaterally. In addition, six cross-sections at C7 were obtained to determine the linear distances between esophagotracheal groove and the recurrent laryngeal nerve. RESULTS: The recurrent laryngeal nerve on the right runs in a superior and medial direction, with an angle of 25.0 degrees +/- 4.7 degrees relative to sagittal plane, compared with 4.7 degrees +/- 3.7 degrees on the left. The length of the recurrent laryngeal nerve between the superior border of the clavicle and the inferior thyroid artery is 23.0 +/- 4.4 mm on the left, and 22.8 +/- 4.3 mm on the right. The recurrent laryngeal nerve lies deep within the esophagotracheal groove on the left, but 6.5 +/- 1.2 mm anterior and 7.3 +/- 0.8 mm lateral to the esophagotracheal groove on the right. CONCLUSIONS: The recurrent laryngeal nerve on the right side is highly vulnerable to injury if ligature of the inferior thyroid vessels is not performed as laterally as possible or if retraction of the midline structures along with the recurrent laryngeal nerve is not performed intermittently. Avoiding injury to the recurrent laryngeal nerve, especially on the right side, is a major consideration during an anterior approach to lower cervical spine.

Aged↗

[Expression of KAI1 gene in human laryngeal carcinoma and its clinical significance].

OBJECTIVE: To explore the mRNA expression of KAI1 gene in laryngeal squamous-cell carcinoma and its clinical significance. METHODS: Fresh laryngeal cancer samples taken from 40 laryngeal carcinoma cases and normal control laryngeal tissues from 9 subjects were examined with semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Moderate, low and negative expression rates of KAI1 gene mRNA in nine normal laryngeal tissues were 33.3% (3/9), 33.3% (3/9) and 33.3% (3/9), respectively. The high, moderate, low and negative expression rates of KAI1 mRNA in 25 laryngeal cancers without lymph node metastasis were 40.0% (10/25), 28.0% (7/25), 20.0% (5/25) and 12.0% (3/25), respectively. The moderate, low and negative expression rates of KAI1 mRNA in 15 laryngeal cancers with lymph node metastasis were 20.0% (3/15), 26.7% (4/15) and 53.3% (8/15), respectively. The KAI1 mRNA expression in the laryngeal cancers without lymph node metastasis was higher than that in normal laryngeal tissues (P < 0.05). The KAI1 mRNA expression in the laryngeal cancers with lymph node metastasis was lower than that in the laryngeal cancers without lymph node metastasis (P < 0.05). The high, moderate and low expression rates of KAI1 mRNA in 10 highly differentiated laryngeal cancers were 50.0% (5/10), 30.0% (3/10) and 20.0% (2/10), respectively. The high, moderate, low and negative expression rates of KAI1 mRNA in 12 low differentiation laryngeal cancers were 8.3% (1/12), 16.7% (2/12), 16.7% (2/12) and 58.3% (7/12), respectively. The differences of KAI1 mRNA expression between high and low differentiation laryngeal cancers were statistically significant (P < 0.05). CONCLUSION: The decrease of KAI1 mRNA expression may be related to lymph node metastasis and low differentiation of laryngeal squamous-cell carcinoma.

Adult↗

Stability of the LMA-ProSeal and standard laryngeal mask airway in different head and neck positions: a randomized crossover study.

BACKGROUND AND OBJECTIVE: The LMA-ProSeal laryngeal mask airway is a new laryngeal mask airway with a modified cuff and drainage tube. We compared oropharyngeal leak pressure, intracuff pressure and anatomical position (assessed fibreoptically) for the Size 5 LMA-ProSeal laryngeal mask airway and the classic laryngeal mask airway in different head-neck positions and using different intracuff inflation volumes. METHODS: Thirty paralysed anaesthetized adult male patients were studied. The LMA-ProSeal laryngeal mask airway and the classic laryngeal mask airway were inserted into each patient in random order. The oropharyngeal leak pressure, intracuff pressure, and anatomical position of the airway tube and drainage tube (LMA-ProSeal laryngeal mask airway only) were documented in four head and neck positions (neutral first, then flexion, extension and rotation in random order), and at 0-40 mL cuff volumes in the neutral position in 10 mL increments. RESULTS: Compared with the neutral position, the oropharyngeal leak pressure for both the LMA-ProSeal laryngeal mask airway and the classic laryngeal mask airway was higher in flexion and rotation (all P < or = 0.02), but lower in extension (all P < or = 0.01). Changes in head-neck position did not alter the anatomical position of the airway tube or the drainage tube. The oropharyngeal leak pressure was always higher for the LMA-ProSeal laryngeal mask airway (all P < or = 0.005) and anatomical position better for the classic laryngeal mask airway (all P < or = 0.04). CONCLUSIONS: The anatomical position of the LMA-ProSeal and the classic laryngeal mask airway is stable in different head-neck positions, but head-neck flexion and rotation are associated with an increase, and head-neck extension a decrease, in oropharyngeal leak pressure and intracuff pressure. The Size 5 LMA-ProSeal laryngeal mask airway is capable of forming a more effective seal than the Size 5 classic laryngeal mask airway in males.

Adolescent↗

Randomized crossover comparison of the proseal with the classic laryngeal mask airway in unparalysed anaesthetized patients.

BACKGROUND: The ProSeal is a wire-reinforced laryngeal mask airway with an additional drain tube that leads to the distal tip of the laryngeal cuff. The design should improve the seal with the larynx. METHODS: The ProSeal and classic laryngeal mask airways were compared in 180 patients in a randomized crossover study. Patients were anaesthetized without neuromuscular blocking drugs. RESULTS: The ProSeal took more time and more attempts to insert successfully than the classic laryngeal mask airway. Insertion was successful on the first attempt in 81% of cases with the ProSeal and 90% with the classic laryngeal mask airway. The ProSeal required more air to achieve an intracuff pressure of 60 cm H2O (6 ml more for size 4 and 12 ml more for size 5). Laryngeal seal pressure was better with the ProSeal than the classic laryngeal mask airway. Median seal pressure was 29 cm H2O with the ProSeal and 18 cm H2O with the classic laryngeal mask airway. Laryngeal seal pressure was greater than 20 cm H2O in 87% of patients with the ProSeal and 41% with the classic laryngeal mask airway. Laryngeal seal pressure was greater than 40 cm H2O in 21% of patients with the ProSeal and in none of the patients with the classic laryngeal mask. Once placed, the ProSeal remained a stable and effective airway. Gastric tube insertion through the drain tube was attempted in 147 cases and was successful in 135 (92%). CONCLUSION: The ProSeal is more difficult to insert than the classic laryngeal mask airway but allows positive pressure ventilation more reliably than the classic laryngeal mask airway.

Adolescent↗

Anatomic considerations of superior laryngeal nerve during anterior cervical spine procedures.

STUDY DESIGN: Cadavers were dissected anatomically to identify the course of the superior laryngeal nerve relative to the spinal column. OBJECTIVE: To illustrate the anatomic relation of the SLN with respect to its vulnerability during anterior cervical spine procedures. SUMMARY OF BACKGROUND DATA: There is ample literature referencing the superior laryngeal nerve with respect to head and neck surgery. Detailed descriptions of the anatomy of the recurrent laryngeal nerve are quite extensive in both the spine and head and neck literature. To the authors' best knowledge, no similar reports have delineated the anatomic relation of the superior laryngeal nerve in procedures on the anterior aspect of the cervical spine. METHODS: Ten dissections were carried out on human cadavers to show the course of the superior laryngeal nerve. Particular attention was directed to the internal branch of the superior laryngeal nerve to show the overall anatomic relation relative to standard landmarks. These landmarks included the superior laryngeal and superior thyroid arteries, the split of the superior laryngeal nerve, and the intervertebral disc space. RESULTS: The superior laryngeal nerve originates from the vagus nerve in the carotid sheath and bifurcates into internal and external branches. Distally, the internal branch of the superior laryngeal nerve courses in close proximity with the superior laryngeal artery and inserts within 1 cm superior to the superior laryngeal artery into the thyrohyoid membrane. With respect to the cervical spine, the distal of portion of the internal branch of the superior laryngeal nerve is located between the C3 and C4 vertebral bodies. CONCLUSIONS: The internal branch of the superior laryngeal nerve supplies innervation to the mucosa of the larynx and has an important sensory reflex that serves to protect the lungs from aspiration. Injury to this nerve can predispose the patient to life-threatening pneumonia. It is therefore imperative for the surgeon to recognize the location and course of this nerve to avoid injuring it. Injury most commonly occurs either by excessive retraction in different planes or by accidental ligation of the nerve.

Cadaver↗

Telomerase reactivation is an early event in laryngeal carcinogenesis.

The exact role and timing of reactivation of telomerase, a key enzyme implicated in cellular immortalization and transformation in the multistep process of laryngeal carcinogenesis, is still unknown. We attempted to (1) determine that quantitative differences exist in the levels of telomerase catalytic subunit (hTERT) mRNA expression among different grades of laryngeal epithelial abnormalities classified according to the Ljubljana classification; (2) determine that telomerase reactivation is an important, most probably early event in laryngeal carcinogenesis; and (3) analyze whether the relative quantity of hTERT mRNA can be used as a molecular biomarker in the early detection of precancerous lesions. The relative quantity of hTERT mRNA, expressed as an hTERT index, was analyzed in 140 frozen laryngeal tissue specimens representing different morphological stages of laryngeal carcinogenesis by using a commercially available LightCycler Telo TAGGG hTERT Quantification kit. The presence and relative quantity of hTERT mRNA in laryngeal epithelium increases progressively with the degree of epithelial abnormalities. hTERT mRNA was detectable in 1/15 normal laryngeal epithelia (7%, mean hTERT index 0.02), 3/15 simple hyperplasias (20%, mean hTERT index 0.09), 10/27 abnormal hyperplasias (37%, mean hTERT index 0.18), 9/12 atypical hyperplasias (75%, mean hTERT index 0.74), 8/9 intraepithelial carcinomas (89%, mean hTERT index 1.82), and 53/62 invasive laryngeal squamous cell carcinomas (85%, mean hTERT index 2.51). Statistical analysis revealed two groups of laryngeal epithelial changes with significant differences in the levels of hTERT mRNA expression (P <.0033): (1) normal and reactive hyperplastic laryngeal epithelium (simple and abnormal hyperplasia) and (2) atypical hyperplasia (precancerous lesion), intraepithelial and invasive laryngeal squamous cell carcinoma. The results of the present study suggest that telomerase reactivation is an early event in laryngeal carcinogenesis, detectable already at the stage of precancerous laryngeal epithelial changes. Nevertheless, other genetic abnormalities appear to be necessary for progression of these epithelial abnormalities toward invasive laryngeal squamous cell carcinoma.

Biomarkers, Tumor↗

[Significance of p53, c-myc and nm23 protein expression in recurrent laryngeal carcinoma].

OBJECTIVE: To evaluate the prognosis of postoperative laryngeal cancer recurrence, the study was designed to investigate the relationship of p53, c-myc and nm23 protein expression in recurrent laryngeal carcinoma. METHOD: Five hundred and seventy-four cases of laryngeal carcinoma were retrospectively reviewed. All the patients were observed for 3 years postoperatively, 56 cases with recurrence were diagnosed and 39 cases of normal laryngeal tissue were compared. The tissue microarrays was made in all the cases. The tissue chip was analyzed by the SABC immunohistochemical method. RESULT: p53, c-myc and nm23 expressed in most of the laryngeal carcinoma. The positive ratio is different. There is higher expression of c-myc in recurrent laryngeal carcinoma, and its expression has significant difference with the laryngeal carcinoma, which have no recurrence (P < 0.01). nm23 has lower expression in recurrent laryngeal carcinoma, and it's expression has significant difference with the laryngeal carcinoma which have no recurrence(P < 0.01). The expression of p53 has no significant difference between recurrent laryngeal carcinoma and the laryngeal carcinoma which have no recurrence(P > 0.05). There is the positive correlation between the expression of c-myc and the recurrent laryngeal carcinoma; and negative correlation between the expression of nm23 and the recurrent laryngeal carcinoma. CONCLUSION: c-myc and nm23 could be the prognosis marker of postoperative laryngeal cancer recurrence.

Adolescent↗

Resolution of laryngeal injury following translaryngeal intubation.

Translaryngeal intubation (TLI) causes mucosal ulcerations of the vocal cords and posterior laryngeal commissure. Usually these ulcers heal by primary reepithelialization, but occasionally laryngeal granulomas or strictures develop at these ulcer sites. The incidence of granuloma and stricture formation and the variables influencing abnormal laryngeal healing following TLI are not well understood. A group of 54 patients who experienced prolonged TLI were followed prospectively to determine the resolution rate of laryngeal injury. Direct fiberoptic laryngoscopy was performed at either extubation or tracheostomy and repeated every 2 wk until the larynx returned to normal or a persistent laryngeal abnormality was identified. Laryngeal symptoms were assessed at these same time points. In 5 patients (9%) the appearance of the larynx was normal at extubation, and in 42 patients (78%) laryngeal healing occurred by primary reepithelialization within 8 wk. Four patients (7%) developed laryngeal granulomas, which required surgical removal in all but one case. No patients in this series developed laryngeal strictures. Three patients (6%) died before complete follow-up. Laryngeal symptoms, particularly hoarseness, resolved as the larynx healed. Performance of tracheostomy, age, TLI for more than 10 days, and severe laryngeal injury at extubation did not influence the median time to resolution of laryngeal abnormalities. Abnormal laryngeal healing following TLI is uncommon but is not exacerbated by prolonged TLI (more than 10 days), severe laryngeal injury at extubation, or performance of a tracheostomy.

Humans↗

Effect of pepsin on laryngeal stress protein (Sep70, Sep53, and Hsp70) response: role in laryngopharyngeal reflux disease.

OBJECTIVES: The objectives of this study were to define the conditions that give rise to a stress protein response in laryngeal epithelium and to investigate whether and how stress protein dysfunction contributes to reflux-related laryngeal disease. METHODS: Western analysis was used to measure stress protein (squamous epithelial proteins Sep70 and Sep53 and heat shock protein Hsp70) and pepsin levels in esophageal and laryngeal tissue specimens taken from both normal control subjects and patients with pH-documented laryngopharyngeal reflux (LPR) who had documented lesions, some of whom had laryngeal cancer. A porcine organ culture model was used to examine the effects of low pH and pepsin (0.1% porcine pepsin A) on stress protein levels. A laryngeal squamous carcinoma (FaDu) cell line was used to examine uptake of human pepsin 3b-tetramethyl-5 and -6 isothiocyanate. RESULTS: Sep70, Sep53, and Hsp70 were found to be expressed at high levels, and pepsin was not detected, in esophageal and laryngeal specimens taken from normal control subjects and in esophageal specimens taken from LPR patients. The patients with LPR were found to have significantly less laryngeal Sep70 (p = .027) and marginally less laryngeal Sep53 (p = .056) than the normal control subjects. Laryngeal Hsp70 was expressed at high levels in the LPR patients. The patients with laryngeal cancer had significantly lower levels of Sep70, Sep53 (p < .01), and Hsp70 (p < .05) than the normal control subjects. A significant association was found between the presence of pepsin in laryngeal epithelium from LPR patients and depletion of laryngeal Sep70 (p < .001). Using the organ culture model, we demonstrated that laryngeal Sep70 and Sep53 proteins are induced after exposure to low pH. However, in the presence of pepsin, Sep70 and Sep53 levels are depleted. Confocal microscopy analysis of cultured cells exposed to labeled pepsin revealed that uptake is by receptor-mediated endocytosis. CONCLUSIONS: These findings suggest that receptor-mediated uptake of pepsin by laryngeal epithelial cells, as may occur in LPR, causes a change in the normal acid-mediated stress protein response. This altered stress protein response may lead to cellular injury and thus play a role in the development of disease.

Adolescent↗

Efficacy of the laryngeal tube by inexperienced personnel.

We compared the laryngeal tube and the laryngeal mask in the ease of insertion, ventilation volume and the incidence of gastric insufflation by inexperienced personnel. In a randomized, cross-over design, each of 28 students of a Fire Defense Academy attempted to insert the laryngeal tube and laryngeal mask in turn using an airway management trainer manikin. A self-inflating bag (2000 ml) was attached and ventilation volume was measured. The number of attempts at the insertion and the presence or absence of gastric insufflation were also recorded. After completion of the study, each student was asked whether insertion of one device was easier than the other. All 28 students could insert the laryngeal tube at the first attempt. As for the laryngeal mask, 27 could insert it at the first attempt, whereas the remaining one student could insert it after two attempts. The tidal volume was significantly greater for the laryngeal tube (median 842 ml) than the laryngeal mask (median 716 ml) (95%CI for median difference: 10-116 ml; P < 0.02). The incidence of gastric insufflation was significantly lower for the laryngeal tube (2 times) than for the laryngeal mask (10 times) (P < 0.05). Twenty six of 28 students stated that insertion of the laryngeal tube was easier than insertion of the laryngeal mask, whereas the remaining two stated that there was no difference in the ease of insertion between two devices. Therefore, the laryngeal tube has a potential role in providing a clear airway during cardiopulmonary resuscitation.

Adult↗

Changes in expression of p53, proliferating cell nuclear antigen and bcl-2 in recurrent laryngeal cancer after radiotherapy.

The biological changes in recurrent laryngeal cancer following radiotherapy are not fully understood. The authors investigated differences in the expression of p53, proliferating cell nuclear antigen (PCNA) and bcl-2 in laryngeal cancer specimens before radiotherapy and in recurrent laryngeal cancer specimens following radiotherapy in the same patients. The authors investigated the expression of p53, PCNA and bcl-2 by immunohistochemical stain in 30 specimens from 15 patients with primary laryngeal cancer and recurrent laryngeal cancer after radiotherapy. The expression of p53 protein was significantly different in laryngeal cancer before radiotherapy (4/15, 26.7 per cent) compared with recurrent laryngeal cancer after radiotherapy (8/15, 53.3 per cent) (p<0.05). The PCNA index was also significantly different in laryngeal cancer specimens before radiotherapy (mean, 11.9 per cent) compared with recurrent laryngeal cancer after radiotherapy (mean, 18.0 per cent) (p<0.05). However, there was no statistically significant alteration of bcl-2 expression in primary compared with recurrent laryngeal cancer. The expression of p53 and PCNA increased in recurrent laryngeal cancers after radiotherapy, compared with that in laryngeal cancers before radiotherapy. Recurrent laryngeal cancers arising following radiotherapy became biologically aggressive.

Biomarkers, Tumor↗

Predictors of outcome in an open label, therapeutic trial of high-dose omeprazole in laryngitis.

BACKGROUND: Gastroesophageal reflux is implicated in some cases of laryngitis. There are no established predictors of response to acid suppression therapy in suspected reflux laryngitis. AIM: In a population with laryngitis, the aim is to determine whether (a) omeprazole 20 mg tds (3 months) improves symptoms and laryngitis, and (b) the outcome in response to potent acid suppression can be predicted by esophageal and/or pharyngeal parameters during ambulatory pH monitoring or by other pretreatment variables. METHODS: From the 70 consecutive patients with laryngitis screened, 20 patients met the inclusion criteria (dysphonia >3 months; laryngoscopically demonstrated laryngitis); and 50 patients were excluded because of one or more criteria indicating alternative causes for laryngeal injury. The primary outcome measure was improvement of at least one level in a 4-point laryngitis grading at 3 months. Twenty-four-hour dual, pharyngo-esophageal pH monitoring was performed at baseline. Secondary outcomes (symptom questionnaire; computerized voice analysis) were measured at baseline, and at 6 and 12 wk. RESULTS: Response rates at 6 and 12 wk were 47% and 63%, respectively. GERD symptoms (heartburn (p= 0.03) and regurgitation (p= 0.0001)) improved. However, neither baseline GERD symptoms nor endoscopic findings predicted laryngoscopic or symptomatic response. Neither baseline laryngitis grade (p= 0.46) nor esophageal acid exposure on pH testing (p= 0.3) predicted outcome. Four of 20 patients demonstrated pharyngeal regurgitation on pH testing, all four of whom responded to potent acid suppression (p= 0.2). Computerized voice measures were not predictive of outcome, although fundamental frequency (Fo) was inversely related to baseline laryngoscopic grade. CONCLUSION: In a carefully defined population of patients with laryngitis (a) 63% have a laryngoscopic response to 3 months of potent acid suppression without significant improvement in laryngeal symptoms; (b) neither voice measures, esophageal acid exposure time, symptoms nor severity of laryngitis predict outcome; and (c) although numbers were small, all patients with a positive pharyngeal pH study responded to therapy and pharyngeal pH-metry may prove useful; (4) available evidence supports an empiric trial of high-dose proton pump inhibitors (PPI), for at least 12 wk, as the initial diagnostic step for suspected reflux laryngitis.

Administration, Oral↗

[Clinicopathological study of squamous metaplasia in human laryngeal ventricles].

A clinicopathological study was performed to clarify the site of onset of primary cancer of the laryngeal ventricles using larynges resected from 22 individuals with no macroscopic lesions in the laryngeal ventricle, and the following results were obtained. 1) Computer graphics were applied to the laryngeal ventricles based on serial sections, and their complex morphology was displayed. 2) Since the morphology of the laryngeal ventricle is complex, the degree of progression of squamous metaplasia differed considerably depending on the morphology of the laryngeal ventricle, even in the same larynx. According to our classification, the "depressed" part exhibited very highly progressive squamous metaplasia in the laryngeal ventricle, and this appeared to be important as a preliminary stage of carcinogenesis. 3) The "depressed" part of the laryngeal ventricle was distributed anteriorly and posteriorly in the ventricle, and this closely coincided with the clinically preferred site of onset of primary cancer of the laryngeal ventricle. On the other hand, the distribution of the "branching" and "separate" parts, with little squamous metaplasia, was mainly in the center of the laryngeal ventricle, which has a low rate of occurrence of primary cancer of the laryngeal ventricle. 4) The metaplastic area in the epithelial membrane of the laryngeal ventricles has previously been reported to be very narrow, but we found that the area was rather broad in some cases. Moreover, the metaplastic area was significantly broadened by smoking and alcohol drinking, demonstrating that the epithelial membrane of the laryngeal ventricles is influenced by these habits.

Adult↗

Recent advances in laryngeal sensorimotor control for voice, speech and swallowing.

PURPOSE OF REVIEW: This article reviews advances in knowledge on laryngeal sensorimotor control affecting the assessment, understanding, and treatment of laryngeal motor control disorders in voice, speech, and swallowing. Three topics are covered: new knowledge on laryngeal innervation and central nervous system control from basic research studies, the role of laryngeal sensation in normal swallowing and dysphagia in patients, and new approaches to the restoration of laryngeal motor control after recurrent laryngeal nerve disorders. RECENT FINDINGS: A significant advance this year was tracing the efferent pathways from the cortex to the brainstem in monkeys. This provided new information on subcortical and brainstem connections in the laryngeal efferent pathways. Laryngeal sensory feedback continued to receive attention, and the role of sensory feedback in the control of the pharyngeal phase of swallowing is now well established. Further developments in neuromotor monitoring of the recurrent laryngeal nerve during thyroidectomy were seen, and a large case series recommended that these techniques become standard practice for surgery for thyroid benign recurrence or malignancy. Finally, the first tissue engineering papers in the field of vocal fold tissue and nerve restoration were published this year, beginning an exciting new approach to restoration of laryngeal motor control. SUMMARY: Considerable attention has been given to laryngeal muscle physiology, denervation, and sensation in neurolaryngology. Relatively limited understanding is available regarding the central nervous system integrative control of laryngeal function for speech, respiration, and swallowing.

Animals↗

Reconstruction of recurrent laryngeal nerve with involvement by metastatic node in esophageal cancer.

BACKGROUND: Recurrent laryngeal nerve paralysis represents one of the major complications in esophageal cancer surgery, and patients with esophageal cancer sometimes develop recurrent laryngeal nerve paralysis before treatment. We evaluated recurrent laryngeal nerve reconstruction in patients with lymph node metastasis infiltrating the recurrent laryngeal nerve. METHODS: Five patients with preoperative recurrent laryngeal nerve paralysis as a result of involvement of metastasis were enrolled in the present study. Ansa cervicalis-recurrent laryngeal nerve anastomosis in the neck was performed in 4 patients and direct anastomosis of recurrent laryngeal nerve in the mediastinum in 1 patient. RESULTS: Six months after surgery, 3 patients who had undergone ansa cervicalis-recurrent laryngeal nerve anastomosis in the neck displayed good quality of life without hoarseness or aspiration. The patient who underwent direct anastomosis of the recurrent laryngeal nerve in the mediastinum experienced occasional aspiration and hoarseness. The remaining patient displayed poor condition because of recurrent lung tumor, and quality of life was decreased. CONCLUSIONS: If patients with recurrent laryngeal nerve paralysis before treatment can undergo potentially curative resection with lymph node dissection, including the metastatic lymph node infiltrating the recurrent laryngeal nerve, recurrent laryngeal nerve reconstruction should be performed to improve quality of life.

Adult↗

Neurotransmitters and neuromodulators involved in laryngeal innervation.

The distribution and role of neurotransmitters and neuromodulators in laryngeal innervation are reviewed, and our recent findings regarding the nitrergic innervation of the larynx are demonstrated for the better understanding of the complexity of the laryngeal innervation system. Noradrenergic innervation of the larynx was studied with fluorescence histochemistry and electron microscopy after application of 5-hydroxydopamine. These studies confirmed the existence of noradrenergic innervation for the submucosal glands and blood vessels, and the origin and course of noradrenergic nerve fibers contained in the laryngeal nerves and their destinations in the larynx. Cholinergic innervation of the larynx has not been clarified in detail. Many kinds of neuropeptides have been demonstrated to be involved in laryngeal innervation. Vasoactive intestinal polypeptide originating from intralaryngeal ganglionic neurons participates in laryngeal vasodilation and reduction of laryngeal seromucous secretion. Neuropeptide Y nerve fibers are few in the larynx, and most originate from the superior cervical ganglion. They are distributed around the large or medium-sized blood vessels, especially arteries. They are also associated with excretory structures. Substance P was the first neuropeptide found to be a sensory neurotransmitter in the laryngeal afferent system. It is also involved in regulation of laryngeal blood flow and secretion. Calcitonin gene-related peptide is associated with the sensory, autonomic, and motor innervation of the larynx. The majority of enkephalin nerve fibers are located close to excretory structures, although no information on the physiological significance of enkephalin is available. In addition to the above neuropeptides, the peptides histidine isoleucine, histidine methionine, and helospectin have been shown to exist in the larynx. The nitrergic innervation of the larynx has been recently studied with NADPH-diaphorase histochemistry and immunohistochemistry using antiserum against nitric oxide synthase. Nitric oxide originates from the neurons in the intralaryngeal ganglia and is believed to modulate blood flow and secretion of the larynx. It controls the laryngeal exocrine secretion in cooperation with intrinsic vasoactive intestinal polypeptide and/or extrinsic calcitonin gene-related peptide. Nitric oxide from the nodose ganglion may modulate nociception of the larynx. The existence of nitrergic neurons located in the intrinsic laryngeal muscles has been demonstrated. Many of them are bipolar or pseudounipolar, so they might be sensory in nature. The effect of injury of the recurrent laryngeal nerve on the induction of nitric oxide synthase in the laryngeal motoneurons is also discussed.

Acetylcholine↗

[Squamous metaplasia of the mucosa of the human laryngeal ventricle: a clinicopathological study with reference to the possibility of de novo carcinogenesis].

Primary carcinomas are rarely encountered in the laryngeal ventricle of Morgagni. They are classified into the subgroup of supraglottic laryngeal carcinoma in the TNM classification system of malignant tumors. However, detailed investigations have not hitherto been made on the possible occurrence of carcinomas in this region of the larynx. To find out whether the laryngeal ventricle could be the site of carcinogenesis, the author examined squamous metaplasia in the mucosal epithelium of 60 human laryngeal ventricles which were taken from 38 larynges removed operatively from patients with laryngeal carcinoma (14 cases), hypopharyngeal carcinoma (20 cases), carcinoma of the upper esophagus (two cases), tracheal carcinoma (one case) or thyroid carcinoma (one case). The patients consisted of 31 males and 7 females, with an age distribution of 44 to 80, average 62.7. The laryngeal ventricles were selected for investigation only when they did not show any carcinomatous invasion macroscopically. Macroscopic observations were performed after gross staining with pyronin Y, which permits differentiation of squamous metaplasia from respiratory epithelia. Tissues were embedded in paraffin, sectioned serially and stained with hematoxylin and eosin. The clinical records of the patients were also made. The results are summarized as follows: 1. Squamous metaplasia of the stratified ciliated epithelium was found in 38 out of 60 specimens (63%) of the laryngeal ventricles examined. 2. The metaplasia seemed to be precipitated by smoking or exposure to radiation, along with aging. 3. The incidence and extent of metaplasia of the ventricular mucosa depended on the disease entity which had necessitated total laryngectomy, and the metaplasia was most prominent in cases with the supraglottic type of laryngeal carcinoma. 4. The metaplastic epithelium was occasionally associated with hyperplasia or dysplasia of the epithelium. 5. Microinvasive carcinoma was found in one laryngeal ventricle with severe metaplasia. These findings suggested a possible de novo carcinogenic process in the laryngeal ventricle through squamous metaplasia of the respiratory epithelium. From this observation, the author proposes to call carcinoma of this region of the larynx the ventricular type of laryngeal carcinoma.

Adult↗

[Expression of adrenomedullin in the tissue with laryngeal carcinoma].

OBJECTIVE: To observe the expression of adrenomedullin (AM) in the patients with laryngeal carcinoma. METHODS: Two-step immunohistochemistry method was used to examine the expression of AM in the patients with laryngeal carcinoma. Radioimmunoassay was applied to determine the concentration of AM in the laryngeal carcinoma tissues, adjacent laryngeal mucosa of carcinoma tissues and in the plasma of patients and controls. RESULTS: Positive stainings for AM were found in all 21 specimen examined,distributed mainly in the cytoplasm of the laryngeal carcinoma cells. Positive stainings were more stronger in the circumference than in the center of tumor tissue for the highly and moderately differentiated tumors. While the stainings were distributed homogeneously for poorly and moderately differentiated tumors. The concentration of AM in the laryngeal carcinoma tissues (n = 44) and the adjacent mucosa (n = 44) were (49.67 +/- 28.33) pg/ml and (14.71 +/- 7.17) pg/ml (x +/- s) respectively and laryngeal tumor showed much higher concentration of AM than the adjacent mucosa (u = 135.00, P < 0.01). The concentration of AM in patients with laryngeal carcinoma of T2, T3 and T4 stage were (31.52 +/- 15.22), (56.63 +/- 18.51) and (96.12 +/- 18.22) pg/ml (x + s) respectively,and there were statistically significant difference among them. In the N stage, patients with higher stages were found to express significantly higher AM concentration, but there was not statistically significant difference between NO stage and N1 stage. In the M stage,patients with M1 stage were found to express significantly higher AM concentration (u = 31.00, P < 0.01). But there was not statistically significant difference between AM plasma concentration of laryngeal carcinoma patients and that of healthy controls. CONCLUSIONS: The results suggested that high expression of AM in tissues of laryngeal carcinoma was related with the TNM stage of laryngeal carcinoma, AM may play an important role in the development of the laryngeal neoplasma.

Adrenomedullin↗