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Time trends of lung and larynx cancers in Italy.

During the period 1970-1989, age-adjusted mortality rates for lung cancer in Italy increased by more than 50%, while rates for larynx cancer in males decreased by approximately 13%. This study aims to interpret this difference, which seems to contradict the finding that cigarette smoking is a common major risk factor for both lung and larynx cancer. To this end, we jointly analyzed the time trends of incidence, survival and mortality. We first examined survival data taken from the population-based Lombardy Cancer Registry (northern Italy). Based on data referring to 880 incident cases of larynx cancer, diagnosed during the period 1976-1987, we estimated a 3% annual increase in relative survival. By contrast, no significant period effect was observed for survival rates of 2,259 incident cases of lung cancer. National incidence rates were estimated using official mortality data and the above-described survival data. Age-adjusted estimated incidence rates increased, from 1970 to 1989, for both cancer sites: +55% for male lung, +56% for female lung, and +22% for male larynx. Moreover, the patterns of birth-cohort effect, which are diverging for mortality, are nearly parallel with regard to incidence. This analysis suggests that a substantial improvement in survival of larynx cancer patients may largely explain the differences in mortality trends for cancer of lung and larynx.

Adolescent↗

Larynx morphology and sound production in three species of Testudinidae.

Although the ability to vocalize is widespread among tortoises, the mechanisms of sound production in chelonians remain undescribed. In this study, we analyze the morphology and histology of the larynx of three species of Testudinidae (Testudo hermanni, T. graeca, and T. marginata) in order to ascertain the presence of vibrating acoustic structure, and based on our findings we propose a general model for phonation in tortoises. The structure of the larynx of the three tortoises analyzed is simple: three cartilages (the cricoid and two arytenoids) form the skeleton of the larynx, while two pairs of muscles (the dilators and constrictors) control the widening and closing of the glottis. The larynx is supported in the oral cavity by the hyoid cartilage, which in tortoises assumes the same functions of the thyroid cartilage of mammals. Two bands of elastic fibers are inserted in the lateral walls of the larynx just upstream of the glottis, and can be stretched away from the hyoid by the movements of the arytenoids. Their position and structure suggest that these bands are capable of vibrating during exhalation, and therefore may be considered vocal cords. The cricoid of T. marginata and T. graeca hold two diverticula, not previously reported, which might function as a low-frequency resonating chamber, improving the harmonic structure of tortoise calls. The structure of the larynx is compared with that of other vertebrates and the relationships between morphology and phonation are discussed. This is the first detailed description of anatomical structures possibly devoted to vocalization in chelonians.

Animals↗

Cytosolic and nuclear androgen receptor activity in the cancer of the larynx.

It is well known that the larynx is a target organ for androgens and the cancer of larynx is more frequent in male subjects. We have evaluated the androgen receptors (AR) in the cytosol (ACR) and in salt extractable (ANR) and salt resistant nuclear fraction (AMR) in a group of 24 male patients with cancer of the larynx surgically removed. In addition specimens obtained from the normal mucosa of the same subjects were analyzed. In 5 patients estrogen (ER) and progesterone (PgR) receptors were also assayed. In all subjects blood samples were taken before surgery for the assay of the following hormones: LH, FSH, estradiol, testosterone, dihydrotestosterone, delta 4-androstenedione, dehydroepiandrosterone sulfate, cortisol. The results observed showed that 18 out of 24 normal larynx mucosa specimens and 17 out of 24 larynx cancer specimens were positive for ACR or ANR or AMR. The 5 samples of normal and cancer tissues analyzed for ER and PgR were negative. In conclusion there is no significant correlation between AR positivity from one size, histology, degree of differentiation and invasivity of the cancer, age of patients and hormonal blood levels from the other. The high ANR and AMR positivity (normal hormonal translocation and binding on DNA acceptors) confirm that the normal and cancer larynx are target tissue for androgens and establish the hormone dependence of this cancer. Hormonal therapy could be envisaged as an alternative or a complementary therapy for this type of cancer at least in the cases in which the analysis of hormone receptors will prove to be positive.

Adult↗

Aromatic DNA adducts in larynx biopsies and leukocytes.

Larynx cancer is strongly associated with tobacco smoking. The objective of this work was an analysis of aromatic DNA adducts in tumour and non-tumour larynx cells by means of the 32P-postlabelling method. Peripheral blood leukocytes were used as a reference tissue. The presence of aromatic DNA adducts was demonstrated in all the studied tissues obtained after surgery of larynx tumours. The highest level of DNA adducts was found in larynx tumour cells, followed by non-tumour larynx cells, which exceeded that found in leukocytes almost 2.5 times. Large interindividual differences were detected between subjects. The adduct level in tumour/non-tumour correlated only moderately. However a high correlation was found between the level of DNA adducts in larynx (tumour and non-tumour) cells and that in leukocytes.

Adult↗

Management of carcinoma of the supraglottic larynx: evolution, current concepts, and future trends.

The treatment of cancer of the supraglottic larynx has undergone an evolution. Better understanding of the anatomy and biology of cancer in this anatomic site has enabled surgeons to devise effective oncologic strategies while making every effort to preserve the function of the larynx. Certain recent concepts and changing trends have emerged in the treatment of cancer of the supraglottic larynx, including the treatment of the neck, significance of extracapsular spread of tumor in cervical lymph nodes, and conservation laser surgery. In 1985, Snyderman et al. reported the prognostic significance of extracapsular spread in patients with cancer of the supraglottic larynx. In 1990, Lutz et al. reported the results of our experience with the treatment of 202 patients. The review verified the significant risk of bilateral neck disease in these patients, even with adjuvant radiation therapy. Accordingly, since 1990 all patients having cancer of the supraglottic larynx have been treated in the Department of Otolaryngology at the University of Pittsburgh with bilateral neck dissections. The use of adjuvant radiation therapy has been based on the presence of extracapsular spread. This study documents the oncologic effectiveness of this treatment and confirms the efficacy of bilateral neck dissections in an attempt to control neck disease and the prognostic significance of extracapsular spread. We review the evolution of the treatment of cancer of the supraglottic larynx, present our results, and consider innovative surgical approaches.

Adult↗

Chondroma and chondrosarcoma of the larynx.

PURPOSE OF REVIEW: The purpose of this review is to give a detailed description of chondroma and chondrosarcoma of the larynx and to put into perspective new findings from recent literature. RECENT FINDINGS: Recent findings indicate that chondroma and chondrosarcoma of the larynx are closely related, either synchronously (areas of both tumor types within the same lesion) or metachronously (malignant transformation of chondroma over time). It is questioned whether the grading of Lichtenstein and Jaffe, and Evans et al. should be used in the larynx, because these grading systems were designed for chondrosarcoma of the long bones. Chondrosarcomas of the larynx seems to behave more like chondrosarcomas of the phalanx, because they too hardly ever metastasize or cause tumor-related deaths. Both CT and MRI play an important role in the workup of these tumors, but they cannot be used to differentiate between both tumor types. No new treatment modalities have emerged recently and surgery is still the treatment of choice. Tracheal autotransplantation may play an increasing role in the treatment of cricoid tumors because it allows for wide resection and optimal revalidation. SUMMARY: It is now firmly established that metastasis in chondrosarcoma is a poor prognostic sign, but is very rare. Without metastasis the prognosis is excellent. Cartilaginous tumors of the larynx are rare. Clinical, radiologic and pathologic characteristics of these tumors are described and a review of treatment modalities is presented. Wide excision with clear margins is usually indicated. The authors recommend that the management of cartilaginous tumors of the larynx be multidisciplinary and centralized in dedicated referral centers.

Calcinosis↗

Influence of glutathione S-transferase M1 and T1 genotypes on larynx cancer risk among Korean smokers.

Glutathione S-transferase (GST) isoenzymes are involved in the detoxification of major carcinogens present in tobacco smoke. It is thus conceivable that deficiency in GST activity due to homozygous deletions of the GSTM1 and GSTT1 genes (the null genotypes) may modulate susceptibility to smoking-induced cancers. The influence of the GSTM1 and GSTT1 null genotypes on larynx cancer risk among the Korean population were evaluated using peripheral blood DNA from 82 larynx cancer patients and 63 healthy controls, all of whom were male current smokers. Increased larynx cancer risk was related to the GSTM1 null genotype (odds ratio (OR)=3.53, 95% confidence interval (CI)=1.27-9.83). The OR associated with the GSTT1 null genotype was also increased, but did not reach statistical significance (OR=1.83, 95% CI=0.70-4.79). Individuals lacking both the GSTM1 and GSTT1 genes were at a significantly higher risk for larynx cancer than individuals with both genes present (OR=4.04, 95% CI=1.33-12.30). These data confirm that the GSTM1 null genotype is an important risk modifier for larynx cancer among Korean smokers and combined GSTM1 and GSTT1 null genotypes could be a useful predictor of genetic susceptibility to larynx cancer.

Adult↗

Primary combined squamous and small cell carcinoma of the larynx: a case report and review of the literature.

Primary laryngeal carcinomas comprise approximately 2% to 5% of all malignancies worldwide. Of these laryngeal carcinomas, approximately 99% are primary squamous cell carcinomas. During the past 30 years, about 160 cases of primary small cell carcinoma of the larynx have been reported. Combined primary squamous and small cell carcinoma of the larynx, the so-called composite tumor of the larynx, is even more rare, with only 13 published cases to date. Although the major risk factors for developing these composite tumors of the larynx are thought to be similar to other more common neoplasms of the larynx, such as squamous cell carcinoma, the treatment and prognosis are different. We report an additional case of combined small cell carcinoma of the larynx and discuss the histogenesis of this unusual neoplasm.

Adult↗

[Induction chemotherapy and larynx preservation: is such practice useful?].

BACKGROUND: Surgery followed by irradiation is considered to be the standard treatment but require frequently a total laryngectomy. Chemotherapy followed by irradiation is available in larynx and hypopharynx squamous cell carcinoma (SCC) treatment. Are results obtained in daily induction chemotherapy usefulness identical to results obtained in larynx preservation studies? PATIENTS AND METHOD: We conducted a retrospective study on patients treated at centre Oscar-Lambret, Lille, from 1986 to 1995, by chemotherapy followed by definitive radiotherapy or by surgery and radiotherapy for laryngeal or hypopharyngeal cancer treatment. All patients were naive of previous head and neck SCC and a surgical treatment, requiring total laryngectomy, should be proposed with curative intent. Induction chemotherapy associated cisplatin (100 mg/m2) on day 1 and 5-fluorouracil (5FU)(1,000 mg/m2) on days 1-4 or 1-5. Irradiation was performed for responders (complete or partial > 50%). If case of non-responder, patients underwent surgical treatment followed by irradiation. We compared results obtained with patients enrolled in clinical trial and with patients whom benefited from this protocol out of trial. RESULTS: Hundred-eight patients were evaluable for purposes of this study. Fifty-two patients were included in clinical trial (group 1) while 56 patients (group 2) were not. There was no statistical difference as regard neither to sex nor to node (palpable or not palpable) and metastasis status between the groups. We found a higher frequency of laryngeal tumour in group 2 (31 vs 17; p =.03). We observed more stage III and less stage IV in group 1. For chemotherapy-related toxic reactions, the exclusive statistical difference observed was haematological toxicity grade III and IV after the second cycle (0 pt in group 1 vs 8 pts in group 2; p =.02). After initial treatment, complete response was achieved without statistical difference between the groups (88.2% vs 78%; p =.27). A surgical procedure was performed in 46 cases without difference according to the reference group and functional larynx preservation was 55.8% (29/52) in group 1 and 53.6% (30/56) in group 2. Whatever the group, causes of death were similarly distributed. Cancer was the first cause of death in both groups. The overall survival of the population (108 patients) was 81.5% at one year, 49.6% at 3 years and 35.3% at 5 years with a median survival of 3 years. There was no statistical difference between both groups. Some parameters influenced the overall survival like T (p =.04), response to chemotherapy (p=.006), extra capsular spread (p = 0.03) and response after completion treatment. CONCLUSION: Induction chemotherapy is available for larynx preservation but cannot be considered as a standard treatment. Nevertheless, results should be reproduced in daily practice with experimented teams as found with non included patient's results. The long-term side effects of such protocols should be evaluated. Recent publication, on increase postoperative infection after chemotherapy, should be evaluated in clinical trial. If confirmed, cost effectiveness of such complication must be integrated in larynx preservation protocols. Larynx preservation remains an interesting point of view for patients but stay an optional procedure and not a reference.

Antineoplastic Combined Chemotherapy Protocols↗

[The expressions of Ki67 and VEGF in squamous cell carcinoma of larynx and the correlation between the two marks].

OBJECTIVE: To investigate the expression of Ki67 and VEGF in squamous cell carcinoma of larynx and the correlation between Ki67 and VEGF. METHOD: The expression of Ki67 and VEGF in squamous cell carcinoma of larynx tissues of 40 cases were studied by immunohistochemical staining. RESULT: The expression of Ki67 and VEGF in squamous cell carcinoma of larynx tissues were higher than those in mucosa of laryngeal cavity (P<0.01). The expression of the two marks in squamous cell carcinoma of larynx with the metastasis of lymph nodes were higher than those without metastasis (Ki67: P<0.05, VEGF: P<0.01). Age and sex did not change the expression obviously (P>0.05). There was a positive correlation between T-stage and immunohistochemical staining (P<0.05). There was also a positive correlation in staining intensity between Ki67 and VEGF (r = 0.823, P<0.01). CONCLUSION: Ki67 and VEGF are objective marks to estimate the behaviors of squamous cell carcinoma of larynx, and they can do help to the diagnosis, the judgment of stages and the treatment of carcinoma of larynx.

Aged↗

[Effect of survivin antisense oligodeoxynucleotide on carcinoma of larynx in vivo and in vitro].

OBJECTIVE: To observe the effect of survivin antisense oligodeoxynucleotide (ASODN) on the apoptosis of human carcinoma of larynx cell line Hep2 and the inhibitory rate in nude mice model so as to discuss the selective blocking activity of antisense technique on gene expression seeking a new way for gene therapy of carcinoma of larynx. METHODS: Antisense oligodeoxynucleotides survivin were transformed into human carcinoma of larynx cell line Hep2 by liposome Lipofectamine 2000. Within 72 h after transfection, 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cellular proliferation. Forty eight hours after transfection, reverse transcription-polymerase chain reaction (RT-PCR) assay was used to observe the expression of survivin gene, Western Blot assay for the protein, and terminal deoxynucleotide mediated nick end labeling (TUNEL) and flow cytometer for cellular apoptosis. RESULTS: Cellular inhibition rate of 72 h went up to 52. 5% and 71.4% at 1.0 micromol/L and 2.0 micromol/L value in Lipo-ASODN groups which differed statistically remarkably (P = 0.046), higher than that in controls in MTT assay (P =0. 003 and 0. 0004). Forty eight hours after transfection survivin gene expression in Lipo-ASODN groups were less than that in control group in RT-PCR assay. Survivin protein expression decreased in Western blot. In TUNEL assay, nuclear positive staining was observed and the apoptosis peak was observed in flow cytometer test, which were absent in controls. In nude mice of carcinoma of larynx model, the inhibitory rate in Lipo-ASODN groups got up to 48.1% and 61.3% higher than that of controls (P < 0.004 and 0. 0006), which differed remarkably (P = 0.032) in a dose-dependently way. CONCLUSIONS: The findings showed that the expression of survivin gene and protein induced cellular apoptosis in Hep2 cells after transfection of Lipo-ASODN and that the carcinoma of larynx in the nude mice model were inhibited by Lipo-ASODN which suggested that antisense technique can be an effective means in the gene therapy of carcinoma of larynx.

Animals↗

[The difference of larynx cancer stage evaluation between clinical and pathological examinations].

PURPOSE: Comparison of stage larynx carcinoma and estimation of hazard dissemination lymph nodes in preoperative clinical and postoperative histological examination according to the TNM staging system. MATERIAL AND METHODS: The group of 100 patients with previously untreated squamous cell carcinoma of larynx was analysed. The material consisted of: 89 man and 11 women of age 39 to 78 year old (average 56). There were 51 patients with supraglottic carcinoma, 39 with glottic carcinoma, 4 with subglottic carcinoma and 6 patients had all larynx occupied. The anaplastic degree checks out brought following results: G1--17 cases, G2--54, G3--13 and 16 cases were not estimated. The diseases stage was defined preoperatively and postoperatively. The number and risk lymph nodes metastases were correlated with the diameter and topographical distribution. RESULTS: The following of clinical examination were estimated: T2--49 patients, T3--40, T4--11. On the case of postoperative histological examination following stages were found: pT2--29, pT3--34, pT4--37. According to clinical nodal staging we found: N0--70, N1--13, N2a--4, N2b--6, N2c--6, N3--1. The postoperative nodal stage verification showed: N0--64, N1--11, N2a--4, N2b--17, N2c--4, N3--0. The harmony of clinical and pathological tumor stage was found in 62 cases and 38 patients were more advanced in pathological examination. In 62 cases the agreement between clinical and pathological N stage was found. In other 38 cases we found different N stage. In group with clinical enlarge lymph nodes 91% cases were metastases. The topographical distribution of the nodal metastases is determined. The most occupied group of lymph nodal are: upper cervical nodes--44%, the mid jugular nodes--31%, submaxillary nodes--14%, low jugular nodes--6%, perilaryngeal--5%. The risk of nodal metastases with diameter to 1 cm is 9% (659 lymph nodal), to 2 cm 15% (48 nodal), above 3 cm (8 nodal) 100%. CONCLUSION: The agreement of larynx carcinoma T stage in clinical examination is considerably incompatible with postoperative pathological examination. In postoperative examination a bigger rate of higher larynx cancer stage was found. The clinical regional lymph node examination is in good agreement with postoperative histological examination. Hazard metastases to lymph nodal is increased in diameter nodal in larynx lesions.

Adult↗

[Treatment of precanceroses and carcinoma of the larynx].

The problem of diagnosis and treatment of precanceroses and carcinome of the larynx is still one of the foremost interests of ENT specialists. In 1973 to 1982 82 patients with precanceroses of the larynx and 174 patients with carcinoma of the larynx were detected and treated. In the treatment of precanceroses of the larynx the laryngomicro-surgical procedure proved useful. In the third stage of Reinke's oedema a satisfactory functional effect was achieved in 100%, in solitary papilloma and papillomatosis in 88%, in leukoplakia and pachyderma in 76% and in chronic hyperplastic in 67%. Least relapses were recorded in the third stage of Reinke's oedema (0%) and in chronic hyperplastic laryngitis (23%). In the treatment of carcinoma of the larynx combined surgical and radiation therapy is preferable and was used in 55.4% patients; in 36.9% patients only irradiation was used and in 7.7% patients only surgical treatment. Within the framework of surgical and combined treatment 52.8% patients were subjected to laryngectomy and 47.2% to various types of partial resections of the larynx. By combined treatment five-year survival was achieved in 67.5% patients; in stage I and II of carcinoma in as many as 87.5% and in stage III and IV only in 47.5%. In patients after actinotherapy five-year survival was attained only in 45% of the patients, and in those with a supraglottic localization of the tumour only in 30%.

Aged↗

The epidemiological risk factors of the larynx cancer among the native and migrant male population.

In the present paper relative risk of larynx cancer has been evaluated in 272 cases in the stationary (native Upper Silesians) (65.4%) and migrant (34.6%) population of men. The corresponding control groups (total 739 men) consisted of 401 (54.3%) and 338 (45.7%) men, respectively, who did not suffer from neoplastic diseases. The important relationship between larynx cancer incidence and cigarette (with or without filter), pipe and cigar smoking has been proved. It has also been shown that the evaluation of larynx cancer risk according to the birth place of populations is more useful, because it enables to discover new epidemiological aspects of the larynx cancer. The higher larynx cancer risk has also been disclosed in men who are in manual work, and who are immediately exposed to the influence of various dusts and gases in their place of work. It has been discovered, that chronic inflammation of the upper respiratory tract, pneumonia, tuberculosis, emphysema or bronchitis also influence higher larynx cancer incidence risk in the native and migrant populations analysed.

Demography↗

Monitoring of antitumor immunity in patients with larynx cancer by tube leukocyte adherence inhibition assay.

The presence of specific antitumor immunity was examined by the tube leukocyte adherence inhibition (LAI) assay in patients with carcinomas of the larynx. Peripheral blood leukocytes (PBL) from patients with larynx cancer gave positive reactions in the LAI assay with the antigen prepared from the carcinoma of the larynx but not with antigen from normal larynx tissue. Adherence of PBL from normal donors did not differ significantly irrespective of whether antigens from tumor or normal larynx tissue were used. With a panel of tumor extracts tested, PBL of some patients reacted to only one antigen, wheras PBL of other patients reacted to several antigens. LAI reactivity disappeared after surgery, reappeared at 4 weeks after surgery, and then declined when patients were tumor free. These results show that the tube LAI assay may be of value in diagnosing larynx cancer and in following up its treatment.

Antigens, Neoplasm↗

Developmental change in the position of the fetal human larynx.

The position of the mammalian larynx has been shown to be an important determinant in breathing, swallowing, and vocalizing patterns. While the growth of the adult human larynx has been studied extensively, detailed examination of fetal development has not been undertaken. Thus, crucial developmental change in the fetal period and the effects of this change on normal maturation are still unclear. This study has examined the development of the larynx and its topography during the fetal period. Thirty specimens were preserved in 10% buffered formaldehyde solution for a period of 6 weeks, after which mid-sagittal sections were performed. Fetal ages were calculated from femur diaphyseal lengths and ranged from 15 to 29 weeks. Direct measurements were taken to determine the growth and position of the larynx and trachea relative to the vertebral column and soft palate. Results show that the upper and lower levels of the larynx correspond to the basiocciput and the lower border of the third to upper border of the fourth cervical vertebrae, respectively. The epiglottic cartilage was present at 15 weeks. By 21 weeks, the epiglottis was well developed and in close palatal apposition. At 23 to 25 weeks, the epiglottis and soft palate were found to be in full contact. The acquisition of this contact may be related to fetal respiratory viability.

Embryonic and Fetal Development↗

Androgen-induced proliferation in the developing larynx of Xenopus laevis is regulated by thyroid hormone.

Exposure to exogenous androgen regulates cell number in the developing larynx of Xenopus laevis and hormone-regulated laryngeal development requires secretion of thyroid hormone (TH). We sought to determine whether exposure to TH is both sufficient and necessary for androgen-evoked cell proliferation (androgen competency) in developing larynx. Androgen competency was not observed in the premetamorphic larynx (tadpole stage 53, before TH secretion) but was present just prior to metamorphic climax (stage 58, during TH secretion). However, when TH is administered precociously (between stages 48 and 50), androgen competency can be observed at stage 53. The stage 52 larynx expresses high levels of the mRNA for TH receptor alpha. The duration of TH exposure required at tadpole stage 48 is greater than 2 days; studies in juveniles indicate that TH exposure need not be maintained in order for androgen competency to persist. The effects of exposure to TH on androgen competency are long lasting and perhaps permanent. While organotypic cultures obtained from tadpoles during premetamorphosis (stage 52) can proliferate in vitro and proliferation is augmented by TH exposure as it is in vivo, precocious exposure to TH does not induce androgen competency. In contrast, androgen does evoke cell proliferation in cultures obtained from metamorphosing (stage 58) tadpoles; proliferation is confined to the cartilage component. Thus, unlike larynges in vivo, muscle will not proliferate in response to androgen, indicating the necessity for an additional factor not present in vitro. Androgen receptor mRNA expression, believed required for androgen competency, was assessed in vivo and in vitro. The tadpole larynx strongly expresses AR mRNA, expression does not require exposure to TH nor is expression diminished in culture.

Animals↗

[Instructions for the complete preparation of the larynx].

A method of preparing the larynx in forensic cases is described especially when death occurs by strangulation (manually or using some form of ligature). After the usual dissection of the hyoid bone and the upper horns of the thyroid cartilage, the complete larynx is clipped and fixed in formaldehyde overnight. The first part of dissection after that is to cut away the thyroid gland and the remaining muscles in front of the larynx, except for the cricothyroid muscle and the esophagus and hypopharynx from the back of the larynx. The complete thyroid cartilage is dissected out, and then a horizontal cut is made through the cricoid cartilage. Median-sagittal halving of the remaining larynx completes the gross dissection. Arytenoid cartilages are exposed by dissection of the arytenoid muscles and opening the cricoarytenoid joints. Now all parts of the laryngeal skeleton and all articulations are examined, and all muscles and soft tissues are visible and can be clipped for histological examination.

Asphyxia↗