Advantages and limitations of the autofluorescent diagnostics of the laryngeal cancer and precancerosis.

Any endoscopic diagnostic procedure that is capable of giving exact information on laryngeal lesions without damaging the tissue has essential advantages over standard biopsy. Tissue autofluorescence is defined as a natural ability of tissue to fluoresce when exposed to a certain light wavelength. This feature is a consequence of the presence of fluorophores in the tissues, which are activated by a narrow wavelength range. However, due to their biochemical and biophysical characteristics, laryngeal precancerosis and cancer do not fluoresce when exposed to blue light. In the present study, we used Pentax's System of Autofluorescent Endoscopy (SAFE 1000) to detect autofluorescence disturbances from laryngeal mucosa. Diagnostic parameters (sensitivity and specificity) of the microlaryngoscopy (MLS) and SAFE 1000 in the diagnosis of laryngeal precancerosis and carcinoma were compared and discussed. We have found that SAFE had a better sensitivity with regard to mentioned laryngeal pathology, but MLS had better specificity than SAFE. The overall diagnostic sensitivity in the diagnostics of laryngeal atypical hyperplasia and cancer with SAFE was 89%, as opposed to 73% with MLS. Diagnostic specificity of SAFE for all cases of laryngeal carcinomas and atypical hyperplasia was 78%. The specificity of MLS in diagnostics of laryngeal carcinomas cases was 98%, while that for cases of atypical hyperplasia was 100%. Many other conditions that have impact on autofluorescent features of laryngeal mucosa were also discussed.

Surgical treatment of the supraglottic laryngeal carcinoma.

This is a retrospective analysis of 439 patients with supraglottic laryngeal cancer primary surgically treated in the period 1976-1999. The objectives of our study were to analyze the localizations as well as local and regional tumor spread, frequency of occult and palpable cervical metastases, the incidence of local and regional recurrences, five-year survival rate and functional results of supraglottic partial horizontal laryngectomies. A retrospective analysis of operated patients was carried out. T1 tumor was prevalent in 184 (42%) patients, T2 in 228 (52%) patients, and T3 tumor in 27 (6%) of cases. Clinically negative finding of the neck was found in 369 (84%) patients, and metastasis N1 was established in 70 (16%) patients. The patients with clinically negative cervical finding underwent selective neck dissection, while N1 metastasis patients were subjected to a selective or modified radical neck dissection. Five-year disease-free survival rate was 76% (334/439).

Alteration of adenoid tissue alkaline and acid phosphatase in children with secretory otitis media.

OBJECTIVE: The role of pharyngeal lymphoid tissue in etiopathogenesis of secretory otitis is not yet defined. The influence of tonsillar and adenoid mass, weight, obstruction of naspharyngeal orrifitium, bacterial reservoire or some immunological events are of scientific interest. Tissue nonspecific alkaline phosphatase (TNAP) and acid phosphatase (ACP) are enzymes detected in lymphoid tissue, TNAP as characteristic of B cells, ACP as a characteristic of macrophages and folucullardentritic cells. These enzymes interfere in cell metabolism by removing 5' phosphate group from nucleotides and proteins. Specific activity and kinetic properties were studied in palatinal tonsils and adenoids of children with secretory otitis (OME) and compared with children with recurrent tonsillitis without ear involvement. METHOD: Adenoid and tonsillar tissue of l7 children with OME and 30 children with recurrent tonsillitis were subjected to biochemical investigation using method of releasing of p-nitrophenol from p-nitrophenylphosphate (pNPP). Kinetic parameters as Michaelis-Menten constant were calculated by non-linear regression estimation method. RESULTS: Specific activity of adenoid alkaline phosphatase was lower in children with OME in relation to children with recurrent tonsillitis (t=5.733507, p<0.01). Specific activity of adenoid acid phosphatase was also lower in children with OME (t=3.655456, p<0.01). pH optimum for both enzymes was the same in these two groups of children. Michaelis-Menten constant for both enzymes was significantly higher in adenoid of children with OME than in children with recurrent tonsillitis suggesting lower enzyme affinity for the substrate. CONCLUSION: Differences in specific activities and kinetic properties of adenoid alkaline and acid phosphatases between children with OME and children with recurrent tonsillitis without OME were verified in this study. The results of the study are not able to explain the alteration of alkaline and acid phosphatase characteristics but could point to some possible and specific role of nasopharyngeal lymphoid tissue in pathogenesis of secretary otitis.

[Possibility of the use of serological method for the determination of immunoglobuline A antibody against early antigene of Epstein-Barr virus as a marker in the diagnosis of nasopharyngeal tumors].

BACKGROUND/AIM: According to the data from immunological, biological and molecular researches, there is a close association between the undifferentiated carcinoma of nasopharyngeal type (UCNT) and Epstein-Barr virus (EBV). To use IgA EA antibody as a serological marker in our patients with nasopharyngeal carcinoma from a clinical viewpoint. METHODS: 91 patients were followed in the period from 1989-1998. In 11 of the patients the antibody titre serum for the early antigen of EBV virus were determinated before the treatement, and in 24 of the patients 3 years after the treatement. There were three control groups of patients: 20 voluntary blood donors, 26 patients with squamocellular laryngeal carcinoma, and 10 patients with squamocellular nasopharyngeal carcinoma. RESULTS: In the group of 11 patients with UCNT before the treatment, the value of anti-EA IgA titre was 31.09, and in the patients after the treatement anti-EA IgA antiody titre was 14.56. In the control groups of patients the results were: in the blood donors 5.00; in the group with the diagnosis of squamocellular laryngeal carcinoma, the titre was 5.00; in the patients with squamocellular nosopharyngeal carcinoma, the titre anti-EA IgA was 5.36. CONCLUSION: These results were statisticly highly significant (p < 0.01). Our research clearly showed that anti-EA IgA EBV marker could be useful in diagnosing, differential diagnosing and prognosing as well.

Chronic laryngitis in glassblowers.

Glassblowers are exposed to numerous physical and chemical noxious factors at their workplace. Mucosal layer of upper aerodigestive tract (nose, oral cavity, pharynx and larynx) is particularly vulnerable to the influence of these factors. Inhalation of hot gases, dust particles, and oral contact with glassblower's pipe are the most important factors that can cause chronic inflammation of the upper respiratory tract. The aim of this study was to examine the prevalence of chronic laryngitis in the group of glassblowers and control group of workers and to examine whether the observed differences depend on the membership in these two groups, on the duration of exposure, or on both factors. The results of the study show significantly higher prevalence of chronic laryngitis among glassblowers than among control group of workers employed in the same plant. On the other hand, the duration of exposure was not statistically significant factor for chronic laryngitis. The exposure to risk factors on the working place represents an independent risk factor for the occurrence of chronic laryngitis among glassblowers, when adjusted for other possible confounders, such as age, years of service, smoking habits and alcohol consumption.

[Treatment of metastatic neck squamous cell carcinomas with unknown primary]. / Terapija metastatskih planocelularnih karcinoma vrata sa neutvrdenim primarnim tumorom.

INTRODUCTION: Treatment of metastatic neck squamous cell carcinomas of unknown primary is one of the most serious problems in head and neck oncology. MATERIAL AND METHODS: Fifty-one patients were analyzed during the period 1977-1997. All patients underwent clinical examination of head and neck, hematological and laboratory tests, X-ray of paranasal sinuses, esophagus and lungs, scintigraphy of the thyroid gland, epipharyngoscopy, esophagoscopy and laryngotracheobronchoscopy, biopsy of suspected changes and blind biopsy of suspected regions (epipharynx, tongue base, piriform sinus), ipsilateral tonsillectomy (17 patients), examination of gastrointestinal tract, kidneys, prostate, testicles, and breasts and ovaries, respectively. RESULTS: Almost half of metastases developed in the II level of the neck (49.01%; 25/51). Most metastases were 3-6 cm in diameter (N2)--60.76% (31/51). Forty patients were surgically treated by various neck dissection methods and postoperative radiotherapy (60 Gy). Palliative radiotherapy was applied in patients with inoperable metastases. Eighteen patients had a five-year disease free survival (35.29%). DISCUSSION: Metastases localized in the II and III levels of the neck and in the upper two-thirds of the V level, should be primarily treated by neck dissection. Lymph nodes up to 3 cm in diameter (N1) are operated by a modified radical neck dissection. Lymph nodes over 3 cm (N2) and 6 cm in diameter (N3) are operated by radical or extended radical neck dissection. CONCLUSION: Primary surgery plus postoperative radiotherapy provide satisfactory results in therapy of metastatic squamous cell carcinomas of the neck with unknown primary.

[Jugular neck dissection for supraglottic laryngeal carcinoma with negative clinical findings in the neck (N0)]. / Jugularna disekcija vrata kod subraglotisnih karcinoma larinksa sa klinicki negativnim nalazom na vratu (N0).

INTRODUCTION: Appropriate management of patients with supraglottic laryngeal carcinoma and negative findings in the neck is still controversial. A prospective and retrospective study comprised 193 patients who were treated primary surgically between 1976 and 1993. They all had clinically and ultrasound negative findings on the neck (N0). Supraglottic carcinomas usually spread regionally. Metastases develop in the jugular group, between level II-IV. The incidence of metastases has been reported to vary from 12 to 62.5%. The size and localization of the primary tumor, its histological grade, genotype of the malignant cells, immunological and other elucidated factors can all affect the incidence of regional spread. AIM: Aim of this study was to specify the incidence of occult cervical metastases; to analyze the distribution of occult metastases related to tumor localization; to specify the distribution of occult metastases related to local spread; to analyze the distribution of occult metastases according to localization in the neck. RESULTS: All patients had primary surgery of primary tumor and bilateral jugular, selective neck dissection at the level II-IV with histological examination of removed lymphoid tissue. Out of 193 patients, metastatic deposits were detected in 35 (18%). Occult metastases were found in patients with carcinoma of the epilarynx in 19% (14/72) of cases, and in 17% (21/121) patients with carcinoma of the supraglottis excluding the epilarynx. This difference in frequency is not statistically significant. The incidence of occult metastases in epilaryngeal tumors did not depend on the degree of local spread. Even relatively small tumors (T1 and T2) yielded occult metastases in 33% (5/15), and 24% (6/25) of patients, respectively. In patients with T1 tumors localized at the supraglottis, excluding the epilarynx, occult metastases were not found. In the supraglottis excluding the epilarynx increased local spread was associated an increase of occult metastases. The incidence of occult metastases was directly related to the degree of the local spread of the tumor in the supraglottis excluding the epilarynx (Table 1). Occult metastases were usually ipsilateral, like the palpable ones. In medially localized tumors bilateral metastases were possible. Ipsilateral metastases were more frequent than both bilateral and contralateral ones. The possibility of contralateral and bilateral occult metastases necessitated bilateral neck dissection. Postoperative radiotherapy (60 Gy) was given to all patients with verified occult metastases. Only in two patients (1%) of the total did metastases develop subsequently, indicating the effectiveness of planned postoperative radiotherapy. DISCUSSION: Controversies in application of jugular, selective neck dissection are present since it has been in use, because of the unclear role which regional lymph tissue play in antitumor immune response. Jugular, selective neck dissection was advocated in all patients with a primary supraglottic laryngeal carcinomas. It was suggested that selective neck dissection was needed only in advanced (T3 and T4) tumors. Selective dissection is believed to be needed only when tumor has spread into the vallecula, the base of the tongue, or the medial wall of the piriform sinus. The idea of selective neck dissection has been opposed since the protective role of the cervical lymph tissue has been stressed. Ultrasound and computerized tomography of the neck cannot detect occult metastases. Today, only removal and histological examination of the lymph tissue can determine occult metastasis. The importance of selective neck dissection is considered in diagnostic biopsy procedure by which occult metastatic spread in the neck region is established. CONCLUSION: Due to the tendency of supraglottic carcinoma resulting in occult cervical metastases, early detection is imperative in order to apply the appropriate therapy. Occult cervical metastases are usually ipsilateral, but bilateral and contralateral may be found as well. Due to the aforementioned, it is necessary to perform bilateral jugular, selective cervical dissection of the neck level II-IV with histological evidence of removed lymph tissue. When metastases is verified histologically, postoperative radiotherapy is indicated as being efficient in hampering the development of palpable metastases. Five-year survival with no evidence disease is 86% (166/193).

Autofluorescent diagnostics in laryngeal pathology.

Autofluorescent diagnostics are based on the ability of oxidized flavin mononucleotide (FMN) in normal cells to emit green fluorescence when exposed to blue light. Neoplastic cells have significantly lower concentrations of FMN and do not emit green fluorescence. Autofluorescent endoscopy is designed for early, accurate and minimally invasive diagnostics for laryngeal pathology. This procedure has the ability to give information about the nature of laryngeal lesions without the devastation of tissue and has important advantages over standard biopsy. In our investigation we used the System of AutoFluorescent Endoscopy (SAFE 1000) designed by Pentax. We examined 38 patients using the SAFE 1000 system, and then all of the patients underwent laryngomicroscopy (LMS). In LMS, a biopsy was taken, and the diagnostic sensitivity of these two methods was compared according to the pathohistologic diagnosis. For statistical evaluation we used Fisher's exact test. We found that autofluorescent endoscopy has greater sensitivity in the detection of precancerous and malignant conditions in the larynx than standard laryngomicroscopy. We believe that autofluorescent endoscopy in addition to laryngomicroscopy gives a more accurate diagnosis of laryngeal pathology than laryngomicroscopy alone.

[New trends in endoscopic diagnosis of tumors of the larynx]. / Novi trendovi u endoskopskoj dijagnostici tumora larinksa.

Early detection and accurate determination of localization and extent of benign growths, particularly precancerous lesions and malignant tumors of larynx have significant therapeutic and prognostic importance. Today, laryngomicroscopy (LMS) is worldwide accepted diagnostic procedure for detection, description and biopsy of laryngeal pathology. In many cases it is a therapeutic procedure. However, detection and accurate description of laryngeal lesion can often be a difficult task, requiring great experience of ENT specialist. Because that attempts to optimize diagnostic procedure for more sensitive detection, and more accurate describing of laryngeal pathology are still challenges for otolaryngologists. Each diagnostic procedure that is able to give accurate information about nature of laryngeal lesion without devastation of tissue has important advantages over standard biopsy. Contact laryngomicroscopy is in vivo microscopic examination of laryngeal mucosa without biopsy. Procedure is performed during laryngomicroscopy by introducing contact endoscope into larynx. Autofluorescent endoscopy is based on ability of flavin mononucleotide (FMN) in normal cells to emit green fluorescence when is exposed to blue light. Neoplastic cells do not have FMN and do not emit green fluorescence. This procedure does not require any substance as a photosenzitizer. Induced fluorescence is based on selective accumulation of protoporphyrine IX (PP IX) in neoplastic tissue that can be detected as a violet fluorescence that emit PP IX. Induction of tumor tissue to fluoresce is achieved with topic or systemic application of 5-aminolevulinic acid (5-ALA). These diagnostic methods have greater sensitivity in detection of tumor than laryngomicroscopy, but have some disadvantages. Combination of laryngomicroscopy and any of these procedures gives more accurate diagnosis than laryngomicroscopy alone.

[Results of supraglottic partial horizontal laryngectomy]. / Rezultati supraglotisnih parcijalnih horizontalnih laringektomija.

INTRODUCTION: Supraglottis is a part of larynx comprising two subregions: epilarynx (suprahyoid epiglottis--including lingual and laryngeal surface, aryepiglottic folds--laryngeal surface, and arytenoids) and supraglottis without epilarynx (infrahyioid epiglottis and ventricular folds). MATERIALS AND METHODS: A total of 234 patients with supraglottic squamous cell carcinoma undergoing primary surgery were analyzed in the period 1976-1996. The tumor was localized in epilarynx in 84 (25%) patients, and in supraglottis without epilarynx in 261 (75%) cases. RESULTS: T1 tumor was present in 145 (42%) patients, T2 tumor was found in 178 (52%) patients, while T3 was reported in 22 (6%) cases. Clinically negative neck (N0) was found in 290 (84%) patients, and palpable metastases (N1) manifested in 55 (16%) cases. Local recurrences were established in 18 (5%) patients, and subsequent postoperative cervical metastases were found in 45 (13%) cases. Five-year disease-free survival was reported in 76% (262/345) of patients. Nasogastric tubes were removed in all patients approximately 12 days following surgery. 27 patients developed laryngeal stenosis and only 2 patients were not decannulated. Voice and speech functions were satisfactory. DISCUSSION: Supraglottic laryngectomy, extended supraglottic laryngectomy is fully justified from oncological and functional aspects. Selective neck dissection in N0 cervical findings provides detection of occult metastases and indicates need for postoperative radiotherapy. CONCLUSION: Oncological and functional results of supraglottic laryngeal surgery, along with simultaneous treatment of neck by selective, modified radical neck dissection and postoperative radiotherapy offer hope for treatment of supraglottic laryngeal cancer.