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[Correlation between expression of the MTA1 gene and carcinomas of larynx].

OBJECTIVE: To study the relation between Mta1 gene (metastasis associated gene, meta gene) and lymph node metastasis of laryngeal carcinomas. METHOD: Reverse transcription polymerase chain reaction(RT-PCR) technique was used to detect the expression of Mta1 mRNA in 30 carcinoma of larynx tissue cases, 12 lymph nodes and 10 normal larynx tissue cases. RESULT: The frequency of MTA1 overexpression was 100% (8/8) in primary carcinomas of larynx with metastasis but only 22.7% (5/22) in toes without metastasis (P<0.01). Expression of MTA1 was 87.5%(7/8) in lymph nodes with metastasis but only 0(0/4) in toes without metastasis(P<0.05). The frequency of Mta1 overexpression was 43.3% (13/30) in primary carcinomas of larynx. CONCLUSION: Our data suggest that the overexpression of the MTA1 gene correlates with lymph node metastasis of carcinomas of larynx. Mta1 gene will probably become a valuable gene for judging metastasis of laryngeal carcinoma.

Adult↗

[Prognostic value of Ki67 and VEGF in squamous cell carcinoma of larynx].

OBJECTIVE: To investigate the prognostic value of Ki67 and VEGF in squamous cell carcinoma of larynx. METHOD: The expressions of Ki67 and VEGF in squamous cell carcinoma of larynx tissues of 32 follow-up cases were studied by immunohistochemical staining, of which five cases recurred(recurrent group), three cases metastasized (metastatic group), eight case died(deceased group) and 24 cased survived(survival group) in three years after operations. RESULT: The expressions of Ki67 and VEGF in deceased group were higher than those in survival group( P < 0.01). Overexpression of Ki67 could be found in recurrent group and in metastatic group (P < 0.01). And VEGF expressed higher in recurrent group than in nonrecurrent group (P < 0.05). On Cox regression of multivariate analysis, Ki67 (RR: 3.236, P < 0.01), clinical T stage (RR: 1.382, P < 0.05) and metastasis of lymph nodes (RR: 0.316, P < 0.05) were shown to be independent prognostic factors for survival of squamous cell carcinoma of larynx. CONCLUSION: Ki67 and VEGF were related to the prognosis of squamous cell carcinoma of larynx, overexpression of the two markers indicated poor prognosis of the disease, and they might be helpful for the treatment of carcinoma of larynx.

Adult↗

[Application of microsurgery in diagnosis and treatment of larynx diseases].

THE AIM OF THE STUDY: was analyzing cases of laryngeal diseases and their location that required treatment by surgical procedure as well as analyzing complications resulting from microsurgery of the larynx and their location during surgical procedures and treatment performed in the Otolaryngology Clinic at Military Institute of the Health Services Central Military Hospital in Warsaw (years 1994-2003). MATERIAL AND METHODS: We analyzed 713 patients, of which 248 were women (34.8%) and 465 were men (65.2%) aged between 12 and 80 (the average age was 49.4 +/- 11.8), who were diagnosed as requiring microsurgery of the larynx using the Kleinsasser's set together with operating microscope and CO2 laser in selected cases. RESULTS: The total of 713 microsurgical operations was performed in the larynx area. The largest group were the patients who were diagnosed as having polyps (33.0%), chronic laryngitis (19.6%) and an established diagnosis of laryngeal carcinoma. Complications were observed in 416 patients (58.3%). CONCLUSIONS: Microsurgery of the larynx was the most often applied form of treatment of vocal fold polyps, chronic laryngitis and laryngeal carcinoma; pathological changes that require microsurgical treatment are mostly located in the epiglottis and the central part of the glottis whilst the major complications resulting from the microsurgery of the larynx are limited to superficial damage of the mucous membrane, mostly on the lips.

Adolescent↗

[Vagal control of larynx resistance to the air flow (author's transl)].

Air flow larynx resistance changes have been recorded in dogs after electrical stimulation and lesion of the recurrent and vagus cervicalis nerves respectively. Experiments were carried out with glottis in situ and isolated. The effects of the administration of athropine i.v. (0.3 mg/kg) were also studied. Air flow larynx resistance decreased after secting the right recurrent nerves as well as after athropine administration. Electrical stimulation of the central end of the right vagus nerve produced a complex response characterized by an initial apnaea followed by a larynx resistance decrease. After a few seconds the response continued with glottis spasms followed by typical emetic movements. During the emetic movements larynx closed and opened throughout the respiratory cycle, the closing movement being simultaneous with the inspiratory position of the thorax and with minimal values of the intraabdominal pressure. Larynx resistance increased after uni- and bilateral sections of the vagus cervicalis and after the electrical stimulation of the peripheral end of the right vagus cervicalis. According to the present results, the possible existence of a controlling reflex of laryngeal sphincter motility, generated at the bronchopulmonary level, is postulated.

Airway Resistance↗

Chondrosarcoma of the larynx. A diagnostic and therapeutic dilemma.

Chondrosarcoma of the larynx. A diagnostic and therapeutic dilemma. Chondromas and chondrosarcomas of the larynx are very rare. Differential diagnosis between benign chondromas and the different degrees of malignancy in chondrosarcomas is difficult. Behaviour of chondromatous tumors of the larynx differs from those of the overall head and neck region. A case of chondrosarcoma of the larynx is described. A literature review regarding chondro(sarco)mas of the larynx and the head and neck region is given presented.

Aged↗

[Toxic habits in relation to cancer of the larynx].

Various modifiable toxic risk factors for cancer of the larynx were evaluated in our geographic area in a retrospective epidemiological study of a sample of 373 patients diagnosed as cancer of the larynx chosen randomly at the La Fe Hospital of Valencia Spain over a 5-year period. A "z" test of the contrast of proportions of the laryngeal cancer series studied and the results of a National Health Survey showed significant differences between the two study populations (p < 0.05). Compared with the National Health Survey, smoking had an odds ratio (OR) of 72.21 (33.10 < OR < 166.31) (p < 0.05, Mantel-Haenszel test). The association between smoking and cancer of the larynx increased with the dose. Alcohol consumption had an OR: 1.52 (1.09 < OR < 2.11) (p < 0.05, Mantel-Haenszel test). Smoking carried a risk of 71.21 and had an etiological fraction of 98.61% (IC 95%: 65.17-100%), thus representing 98.61% of all etiological factors. Control of smoking could have prevented 65.17-100% of cases of cancer of the larynx (243 cases in our series). Alcohol consumption had a risk of 0.52 and etiological fraction of 34.21% (IC 95%: 2.38-100%). Control of alcohol use could have prevented cancer of the larynx in 2.38-100% of cases (9 cases in our series).

Adolescent↗

Oat cell carcinoma of the larynx and Eaton-Lambert syndrome.

Oat cell or undifferentiated small cell carcinoma is a rare malignant tumor of the larynx. Since this lesion was first described, only 23 cases have been reported in the literature. Oat cell carcinoma of the lung, however, accounts for 20% to 25% of all lung cancers and is frequently associated with a variety of paraneoplastic syndromes. A 64-year-old woman had a primary oat cell carcinoma of the supraglottic larynx associated with clinical and electromyographic evidence of the myasthenic syndrome of Eaton-Lambert. To our knowledge, this is the first description an oat cell carcinoma of the larynx associated with this syndrome, which supports the theory that oat cell cancers of the larynx and lung have a common histogenesis.

Carcinoma, Small Cell↗

Hyaluronan localization in the rabbit larynx.

BACKGROUND: The larynx is a complex organ composed of different connective tissue elements. So far, the extracellular matrix of the larynx has not been thoroughly described. Hyaluronan is a matrix polysaccharide with physicochemical effects and biological cell functions in soft connective tissues. METHODS: The histochemical distribution of hyaluronan (hyaluronic acid, hyaluronate) was studied in tissue sections from various levels of the rabbit larynx by means of a hyaluronan-binding protein and avidin biotin peroxidase staining. Microwave-aided fixation was used to retain the extracellular location of hyaluronan. RESULTS: Hyaluronan accumulated chiefly in the subepithelial lamina propria and in the connective tissue enclosing striated muscle fibres of the thyroarytenoid muscle and vocalis muscle. This localization contrasted sharply with the weak staining for hyaluronan in muscles external to the thyroid cartilage. Intensive staining for hyaluronan was found in perivascular and periglandular connective tissue, as in the vacuoles of the hyaline cartilage of the thyroid, cricoid and arytenoid cartilages, and to a lesser extent in the lacunae of the chondrocytes and in the perichondrium of the elastic cartilage of the epiglottis. CONCLUSIONS: Hyaluronan was heterogenously distributed in the rabbit larynx. It was abundant in intrinsic laryngeal muscles performing small, precise, and rapid movements and in the subepithelium at the glottic level, where it may facilitate mucosal movements. The abundant hyaluronan in the subglottic region may be involved in the control of vascular leakage and edema formation.

Animals↗

Larynx-associated lymphoid tissue (LALT) in young children.

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) plays a central role in mucosal immunity. Whereas the characteristics and function of MALT in the intestine are well established, almost nothing is known about MALT in the larynx. METHODS: In this study we examined the morphology and the lymphocyte subset composition of MALT in the larynges of children who had died of sudden infant death or various defined traumatic or nontraumatic causes. RESULTS: Organized lymphoid tissue was found in the supraglottic parts of the larynx in nearly 80% of the children in both groups. This lymphoid tissue showed all morphological signs of MALT, such as typical lymphoid follicles with germinal centers, infiltration of the overlying epithelium by lymphocytes, and high endothelial venules (HEV). Thus we will use the term LALT (larynx-associated lymphoid tissue) to refer to this tissue. The lymphoid follicles of LALT contained mainly B lymphocytes with some CD4+ lymphocytes in the germinal centers. Remarkably, T lymphocytes of both subset types and B lymphocytes were observed in comparable numbers in the parafollicular area. CONCLUSIONS: We assume that LALT is a physiological structure of the larynx in young children. The morphology and the distribution of lymphocyte subsets are similar to those of MALT in the human gut. LALT may be a regular part of the mucosal immune system in young children with the role of respiratory inductive site for mucosal immunity.

Antigens, Differentiation, B-Lymphocyte↗

Comparative cytochrome P450 -1A1, -2A6, -2B6, -2C, -2D6, -2E1, -3A5 and -4B1 expressions in human larynx tissue analysed at mRNA level.

The metabolic activation of numerous exogenous and endogenous chemicals is catalysed by cytochrome P450 enzymes (CYPs). The aim of this study was to analyse the expression of the individual forms of CYP at the mRNA level in human larynx and quantitatively to compare their expressions in human liver, the main organ of CYP expression. Individual forms of CYP mRNAs were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) using specific primers for the CYPs -1A1, -1A2, -2A6, -2B6, -2C, -2D6, -2E1, -3A3/4, -3A5, -3A7 and -4B1. An RNA competitor of known copy number, covering the primer sequences necessary to amplify the entire object CYPs within a single molecule, was used as reference. This study reports a consistent detection of mRNAs for the CYPs -1A1, -2A6, -2B6, -2C, -2D6, -2E1, -3A5 and -4B1 in the human larynx tissue. The data indicate that the human larynx highly resembles the lung tissue in CYP content, as a comparable subset of CYP mRNAs was detected in the larynx previously reported for human lung with the exception of CYP1A2. The results are discussed in quantitative ratios of the detected CYP mRNAs in relation to the hepatic CYP expression.

Aryl Hydrocarbon Hydroxylases↗

Latent Human Papillomavirus infection is comparable in the larynx and trachea.

Recurrent respiratory papillomas are benign airway tumors caused by Human Papillomaviruses (HPVs) types 6 and 11. The disease is characterized by multiple recurrences of papillomas following surgical removal, caused by activation of latent HPV DNA. Most patients have laryngeal disease, while only a small subset has tracheal involvement. We have asked whether the lower frequency of tracheal papillomas was due to reduced prevalence of latent/subclinical tracheal HPV infection or reduced likelihood of activation to clinically apparent disease. A total of 121 biopsies of clinically normal laryngeal and tracheal tissues from 61 patients with laryngeal papillomas were analyzed for HPV DNA by polymerase chain reaction, confirmed by Southern blot hybridization. Patients were followed for 3-18 years (mean = 5.5 +/- 4.4), with only one developing subsequent tracheal disease. There was no significant difference in prevalence of latent HPV DNA between larynx and trachea, analyzing either those patients with a single biopsy or those with more than one biopsy of larynx, trachea, or both. There was also no significant difference between tracheal latency with HPV 6 and HPV 11. We conclude that HPV infects tracheal mucosa and is maintained as a latent infection in the trachea as efficiently as in the larynx. Therefore, we propose that the low frequency of tracheal disease reflects a lower frequency of HPV activation, and postulate that cellular factors that differ between the stratified squamous epithelium of the larynx and the ciliated pseudo-stratified columnar epithelium of the trachea contribute to this difference.

Adolescent↗

Irradiation influences the expression of substance P and enkephalin in the rat larynx.

The effects of radiotherapy on neuropeptide expression in the rat larynx were studied. Irradiation was given for five days, 6 or 8 Gray daily. Ten days after the end of irradiation, the larynx, the laryngeal nerves and different ganglia related to the larynx were dissected out from irradiated and control animals and processed for neuropeptide immunohistochemistry. There was an increased immunolabelling for two of the neuropeptides tested, substance P and enkephalin, in the innervation of the subglottic glands and in the acetylcholinesterase-positive ganglionic cells of the local ganglia. These cells were interpreted as representing postganglionic parasympathetic ganglionic cells. The changes seen in the subglottic glands were interpreted as most likely being related to the changing pattern of staining seen in the local ganglia. No changes in substance P- and enkephalin expression were observed in other laryngeal structures, the nodose ganglia, superior cervical ganglia or laryngeal nerve paraganglia. Thus, in certain respects neuropeptide expression in the larynx is modulated by radiotherapy. Since neuropeptides have both neurotransmitter and/or neuromodulator effects in airway tissue and since they show effects as growth factors, the occurrence of this plasticity in neuropeptide expression should be taken into consideration in future studies examining the effects of irradiation on normal/diseased airway tissues.

Animals↗

[Larynx lesions and sudden death (author's transl)].

Several recently observed cases of "Sudden Death" caused by larynx lesions give reason for a special discussion of this problem. At the Institute of Legal Medicine only six cases were found in 10.747 autopsies between 1949 and 1970. A brief description of the anatomical structure of the larynx is followed by a discussion of the 4 general pathological entities, which might be the etiological cause of laryngeal obstruction: 1. Abnormalities 2. Disturbances of circulation 3. Inflammations 4. Tumors Besides the question of the forensic-medical importance of such fatal cases, the difficulty of evaluating some of the patho-morphologic and histologic findings is discussed. Simultaneously attention is drawn to the frequent lack of a clinical history, so that life-supporting measures wuch as tracheotomy and others are applied very late or not at all. Finally the problem of forensic evaluation of larynx-cysts and their etiology is presented. In this context the clarification of a causal relationship with possible previous intubations of the larynx is of major importance.

Adult↗

[Physiology of the larynx].

The larynx consists of the cartilaginous-osseous framework, elastic membranes and ligaments, joints, muscles, nerves, vessels, and interior cavity. The laryngeal functions are the protection of the airway during swallowing, respiration (i.e. maintainance of the airway) and phonation. During the pharyngeal phase of swallowing the swallow reflex induces a laryngeal closure in three levels and a superior-anterior movement of the larynx and hyoid bone. The laryngeal airway is maintained by the circumference of the cricoid cartilage. Phonation is the phylogenetically recent function of the larynx and was made possible by the laryngeal descent. The sound production is explained according to the myoelastic-aerodynamic theory. The diagnostics of laryngeal diseases is performed in close cooperation between otorhinolaryngology and radiology. For diagnostic purposes, the physiology of the larynx requires to take into account not only morphological, but also functional aspects.

Airway Resistance↗

Comparative morphology of the hyo-laryngeal complex in anthropoids: two steps in the evolution of the descent of the larynx.

The descent of the larynx is a key phenomenon not only in postnatal development, but also in the evolution of human speech. The positional change of the larynx is affected by the descent of the hyoid bone in relation to the mandible and cranial base, and that of the laryngeal framework in relation to the hyoid bone. The phylogeny of the spatial configuration of the hyo-laryngeal complex is one of the most important sources of information for elucidating the evolution of laryngeal descent. In the present study, the anatomy of the complex was examined in various species of anthropoids to compare the configuration, the shape of the basihyal and thyroid cartilage, and the length of the lateral thyrohyoid ligaments. Non-human hominoids share most features with humans, while cercopithecoids and ceboids have anatomical features that sharply contrast to humans, except for the form of the thyroid cartilage in ceboids. The laryngeal framework in hominoids is well separated from and assured of mobility independent of the hyoid. In cercopithecoids and ceboids, it is, by contrast, locked into and tied tightly with the hyoid so that the hyo-laryngeal complex acts as a functional unit. This spatial configuration is considered to be significantly related to the mechanism that prevents aspiration, including epiglottic movement and vestibular closure. Non-human hominoids are inferred to share the mechanism with human adults, not with cercopithecoids and ceboids, although their larynx is located as high as the latter. Consequently, it is hypothesized that the descent of the larynx evolved in two steps. The first step would have been descent of the thyroid in relation to the hyoid for the evolution of the mechanism preventing aspiration, which occurred in the common ancestor of hominoids. The second step, descent of the hyoid within the neck, occurred during hominid evolution for human speech.

Adult↗

Human larynx expresses isoforms of the oestrogen receptor.

Commercially available enzyme immunoassays (EIAs) were used for oestrogen (ER) and progesterone (PR) receptor determination in the cytosol fraction of 118 human larynx cancer specimens and in the corresponding histologically proven non-malignant tissues. Fifty-one ER positive cancerous samples had corresponding non-cancerous tissues also expressing the receptor. A high resolution isoelectric focusing (IEF) technique followed by immunoblotting with the H222 anti-ER monoclonal antibody was used to evaluate the presence of ER isoforms in the 51 ER positive human larynx cancer specimens and in their corresponding non-malignant tissues. In both tissues, four ER isoforms were detected, with isoelectric points (pI) similar to those obtained in breast and endometrium carcinomas (6.1, 6.3, 6.6 and 6.8). A significant difference in the expression of ER isoforms between cancerous and non-cancerous tissue was found; precisely, the 94.1% of the ER positive non-malignant specimens co-expressed the four isoforms while they were detected in only the 35.5% of the malignant specimens (P < 0.0001 by Fisher's exact test). In larynx cancer, the concentration values of ER and PR did not correlate, nevertheless tumours co-expressing the four ER isoforms had PR levels significantly higher than those which did not (P = 0.02 by Mann-Whitney Wilcoxon sum rank test). To investigate the possibility that the isoforms of the monomeric 4S form of the ER (those with pI 6.3, 6.6, and 6.8) could dimerise, a cold agarose gel electrophoresis technique was used on IEF-separated ER isoforms. In summary, the evidence shows that all the isoforms are able to form homodimers and that the isoforms at pI 6.3 and 6.8 are able to dimerise with that at pI 6.6 but, under the same experimental conditions, they do not form the 6.3/6.8 heterodimer. It was concluded that: (1) the four isoforms of the ER are co-expressed by the non-malignant human larynx and the cancer loses the capacity to express some of them; (2) the complete complement of ER isoforms (all four) is needed for PR expression; (3) the monomeric 4S isoform with pI 6.6 has the capacity to form homo- and heterodimers, while the remaining two are only able to homodimerise.

Breast Neoplasms↗

Larynx motion associated with swallowing during radiation therapy.

PURPOSE: A basis is presented for predicting the reduction in radiation dose to the larynx attributable to swallowing during radiation therapy treatment. METHODS AND MATERIALS: Laryngeal movement associated with swallowing can occur during radiation therapy even when the patient's head is immobilized. Data on the extent and timing of laryngeal motions and the frequency of swallowing were used to predict the effect such motion would have on accuracy of radiation dose to the larynx. RESULTS: In a nontracheostomized adult the larynx elevates approximately 2 cm during a swallow and moves anteriorly less than 1 cm. The normal frequency of swallowing in the supine position is once every 1-2 min. During therapy, the likelihood of a swallow occurring during an irradiation interval depended on the duration of the interval. For irradiation intervals less than 2 min long the ratio of number of swallows to number of intervals was 0.27. For irradiation intervals between 2-3 min long the ratio was 1.76. Based on conservative estimates of radiation field dimensions, larynx motion, and incidence of swallowing, the reduction in radiation dose attributable to swallowing during treatment would be approximately 0.5%. CONCLUSION: With small fields the total dose is only decreased by 0.5% with swallowing, so the change in the total dose is insignificant.

Deglutition↗

Immunohistochemical and immunoradiometric evaluations of total cathepsin D in human larynx.

By using a commercially available immunoradiometric technique (Cath-D-IRMA, Cis BioInt.) the distribution of total cathepsin D (cath-D) in 30 malignant and in the corresponding histologically-proven non-malignant fragments obtained from lymph node negative patients suffering from larynx cancer was investigated. In both tissues the oestrogen and progesterone receptors were also assayed. In 17 out of the 30 samples, the cath-D was also assayed by immunohistochemistry using the M1G8, a mouse monoclonal antibody raised against cath-D (Cis BioInt.). Our data indicate that cath-D is present in prismatic cells of the normal laryngeal epithelium and in the cancerous cells. In cancerous larynx, the outer cell layer of large tumour nests showed the highest degree of immunoreactivity, while fibroblasts and inflammatory cells always showed a very faint staining. Cathepsin D levels were significantly higher (P < 0.0001) in the cancerous fragments (with a mean of 33 +/- 3.4 pmol/mg protein) than in the corresponding non-cancerous specimen (with a mean of 20.8 +/- 2 pmol/mg protein). A significant positive association (P < 0.001) between cath-D and progesterone receptor (PR) concentration values in the cancerous larynx was observed; accordingly, tumours expressing PR had significantly (P = 0.0005) higher cath-D levels than the tumours which did not contain the receptor. In contrast, such a relationship was absent in the non-malignant specimens. As regard the oestrogen receptor, no significant relationship between this and cath-D was observed. We conclude that cath-D measured by IRMA in tissue cytosols is mainly derived from cancerous cells, the contribution from fibroblasts and inflammatory cells being negligible. Cathepsin D overexpression and association with the PR in the malignant part of the larynx could indicate a possible role of the receptor in the biology of this disease.

Aged↗