Differential integrin expression in thyroid and laryngeal carcinomas.

Several laryngeal and thyroid carcinomas were studied immunohistochemically to evaluate whether the expression and distribution of integrins and basal lamina components can represent reproducible markers for correct early diagnosis and prognosis. In laryngeal cancers, the depolarization and pericellular redistribution of alpha 3 beta 1 and alpha 6 beta 4, and focal or massive fragmentation of the basal lamina, according to tumor prognosis, occurred. In thyroid carcinomas, loss of polar topography of alpha 3 beta 1 and neo-expression of alpha 6 beta 4 in histopathologically or clinically aggressive cancers were observed. Therefore, the addition of a panel of adhesion molecules to the toolbox of surgical pathologists may improve diagnostic and prognostic procedures.

Expression of antigens associated with the individual stages of the inflammatory response in child and adult as a possible distinctive method for recurrent and chronic tonsillitis.

Monoclonal antibodies (MoAbs) specific for the antigens associated with each stage of an inflammatory response were assayed with tonsillar mononuclear cells (TMNG). MoAbs BMA 27 E 10 and BMA 4 D 10 were used as markers for the early stages, BMA RM 3/1 for the intermediate stage, BMA 25 F 9 for the late stage, and BMA G 16/1 for the chronic stage. TMNC were obtained from patients operated for (1) recurrent tonsillitis with hypertrophy caused by common flora (children); (2) an indication for surgery for chronic tonsillitis in adults; (3) patients who were 'warm' tonsillectomized for a second peri-tonsillar phlegmon. Our results are presented and discussed in the light of their possible clinical significance. Our findings indicate that clinical chronic tonsillitis in the adult really is such. In the adults studied there was a high expression of antigens which is associated with the chronic stages, while the low expression of antigens is associated with the intermediate stage and an even lower antigen expression indicates the acute stage. In children what is considered to be chronic tonsillitis may perhaps be more correctly regarded as an expression of recurrent inflammation.

Immunological investigations on tonsillar and peripheral blood lymphocytes after adeno-tonsillectomy. Possible suggestions for phenotypical and functional differences.

The phenotypical and functional aspects of tonsillar (TMNC) and peripheral blood mononuclear cells (PBMNC) obtained from 40 patients who had undergone adeno-tonsillectomy for different tonsillar diseases were investigated. TMNC and PBMC were separately tested at the time of surgery; then a further investigation on the peripheral blood lymphocytes was performed three months after surgery. The most interesting findings are presented and discussed with particular attention to their clinical implications.

Integrin expression in head and neck cancers.

Neoplastic transformation results in rearrangement of the cell membrane with a breakdown of the regular expression of adhesion molecules such as integrins. A relationship may exist between the intensity of this alteration, and the form it takes, and a tumour's ability to metastatise. We studied this possibility by investigating the epithelial integrin expression of 35 head and neck squamous cell carcinomas. Two types of positivity were observed: one associated with tumours with a better prognostic index, the other with those characterized by greater malignancy.

Is transposed skin transformed in major head and neck mucosal reconstruction?

We used histological and histochemical methods to investigate the possible changes with time in skin transposed into the oropharynx and oral cavity of patients whose surgical wounds were reconstructed with the classic pectoralis major flap. We found histological evidence that skin morphology was maintained (keratinization with reduced, but the desquamating layer, hair follicles, sweat and sebaceous glands were identifiable), and noted an intense inflammatory reaction in the dermis. Histochemical studies confirmed the progressive flattening of the basal interdigitations between the epithelium and dermis, and the gradual reconstruction of the basement membrane. Although skin-mucosa continuity developed fairly quickly without scar reactions, the two epithelia maintained their original patterns of keratin production, i.e., their textural peculiarities. We propose an original method for the transposition of muscular flaps implanted with autologous culture of keratinocytes, an approach developed in an attempt to ensure more satisfactory rehabilitation of the removed mucosal structures.

Mucosal immunity in allergic rhinitis.

Secretory IgA (SIgA) is the main agent protecting the mucosal districts against both infectious microorganisms and inert foreign macromolecules. A lack of secretory immunity has previously been described in patients with allergic rhinitis, but it is a controversial finding. The discrepant results of SIgA levels found in allergy may partially be due to methodological problems. Sixty patients with previously demonstrated allergic rhinitis, treated or not with specific desensitization therapy and free from clinical manifestation of rhinitis were studied. Normal volunteers and patients with selective 11S IgA deficit, without allergic pathology, were investigated as controls. The titration of SIgA in nasal secretions, performed by an original immunoisoelectro-focusing method, showed significantly decreased values in allergic patients. An evaluation of the IgE level in nasal secretion was performed by ELISA. Low rates of IgE were also found in the intercritic period.

Significance of adhesion molecules as biological prognostic factor in locally advanced laryngeal squamous cell carcinomas.

Thirty laryngeal carcinomas were studied immunohistochemically in order to evaluate whether the expression and different distribution of adhesion molecules influence the clinical features and progression of the tumors. On the basis of clinical and pathological variables, two different groups were established: one with good and the other with poor prognosis. The patients were included in one of the two groups on the basis of prognostic factors previously studied by multivariate analysis (the validity of this choice was confirmed by the NED survival curves of the two groups). Different integrins, type I and V laminin and type IV collagen were evaluated by means of monoclonal antibodies in the tumoral specimens and in normal mucosa. Univariate statistical analysis was performed to evaluate differences between the two groups. The degree of expression and pattern of distribution were different in tumor compared with normal mucosa and significant differences were found between the good- and worst-prognosis tumors.

[Phenotype expression and production of IL-2 by tonsillar and blood lymphocytes in patients with tonsil pathology]. / Espressione fenotipica e produzione di IL-2 da parte di linfociti tonsillari ed ematici in soggetti con patologia tonsillare.

In recent years several studies have attempted to investigate immunological responses in different tonsillar pathologies, including recurrent tonsillitis and focal infections. The present study was performed on ten patients who had undergone tonsillectomy for a) simple hypertrophy, b) recurrent tonsillitis and c) recurrent tonsillitis with focal manifestations. The blood (PBMNC) and tonsillar (TMNC) lymphocytes were tested separately. A subsequent investigation was performed on the PBMNC six months after surgery. The phenotypical aspects of the different subpopulations were studied using fluorescent antiserums and monoclonal antibodies. A second field of investigation concerned the in vitro blastogenesis, which was measured under spontaneous and PHA-P induced conditions. Finally, the IL-2 production was evaluated using the induced-growth capacity of an IL-2 dependent clone of a T murine cell line. The most interesting findings are presented. The phenotypical studies confirmed some peculiar aspects of the representation of tonsillar subsets. According to the hyperactivation ratio, the proliferation data proved to be higher in the tonsil than in the blood. A greater number of positive HLA-DR and IL-2 receptor cells (both antibodies being activated cell markers) was seen in the tonsil than in the blood and this, as well as the sporadic presence of spontaneous blastogenesis, suggests the possibility of an in vivo pre-activated condition. As far as the secretion of IL-2 is concerned, when compared to the peripheral blood ratio, greater production was found in the tonsil. Finally, a different production kinetic appears to be a constant result of the present study. The performed tests were unable to demonstrate any particular differences among the three different groups of pathologies.

[Local immunity following treatment with S-carboxymethylcysteine-lysine in tracheotomy patients]. / Immunità locale in seguito a trattamento con S-carbossimetilcisteina sale di lisina nei soggetti tracheotomizzati.

Pathological modification in secretory IgA values as well as in circadian rhythms were found in tracheotomized patients in both nasal and tracheo-bronchial secretions. The protective role of the mucosal immune system in addition to the frequency of severe infectious respiratory diseases in laryngectomized patients justifies the efforts of clinicians to prevent and treat such modifications. Mucoregulatory drugs have a peculiar role in these therapeutical attempts. Forty tracheotomized subjects with neoplastic disease were studied. Twenty received SCMC-Lys as a mucoregulatory drug. IgA 7S, 11S and albumin values in nasal and tracheo-bronchial secretions, were evaluated at surgery, 15 and then 40 days later. In accordance with clinical data, an improvement in local antibody production, damaged by tracheostomy, was found in the treated group. The influence of SCMS-Lys on SIgA production, whose evaluation was made by means of an original, highly selective and sensitive Immuno-IsoElectroFocusing procedure, seems to encourage the use of mucoregulatory drugs in laryngectomized patients.

[Determination of 11S IgA in nasal secretions in the monitoring of local immunomodulating therapy]. / Il dosaggio delle IgA 11S nel secreto nasale nel monitoraggio delle terapie immunomodulanti locali.

Twenty pediatric patients with recurrent infectious diseases of the upper respiratory tract (tonsillitis, adenotonsillitis with or without involvement of the ear and/or lower respiratory tract) were studied. An immunological assay of the nasal secretum was performed at time of diagnosis and following treatment with a local immunomodulator drug, administered by spray. The 7S, 11S IgA and albumin rates were evaluated. The authors emphasize the importance of SIgA in mucose defense mechanisms as well as the need for a selective method for determining the 11S IgA level. An original method for immuno-isoelectrofocusing (IIEF) determination was employed in the present study. After treatment a significant increase in 11S IgA level was observed, especially in those patients with a significant basal SIGA deficit. The authors describe details of the technique for determination and discuss the results.

[The problem of recurrence of rhino-sinusal polyposis: pilot trial with locally administered azelastine HCL in the prevention of relapses]. / Il problema delle recidive dei polipi naso-sinusali: studio pilota sul possibile impiego per via topica dell'azelastina HCL nella prevenzione delle recidive.

Recurrent nasal polyposis is one of the most common unsolved problem in clinical rhinology. In the last few years a great number of histopathological, immunohistochemical and immunological studies on nasal polyps have been carried out by several Authors. Notwithstanding this, the aetiology of these formations still remains unknown. Many data suggest that the presence of polyps is the result of various inflammatory, allergic and pseudo-allergic processes which finally lead to the formation of the oedema constitutive of the polyp itself. In the present report a preliminary trial was carried out in order to evaluate the possibility of preventing recurrences by means of a locally administered anti-H1 receptors drug (Azelastine HCl). In the reported first phase of the study 10 allergic patients with bilateral polyposis were evaluated. Attention was given to the anti-edemigen activity of the drug, as well as to its influence on the local production of Secretory IgA, 7SIgA and albumines. Data are presented and discussed.

[Adhesion molecules in squamous cell carcinoma of the larynx: possible indication of prognosis]. / Le molecole di adesione nel carcinoma squamoso della laringe. Possibile significato prognostico.

Thirty patients with laryngeal tumors were divided into two groups on the basis of whether clinical and pathological features indicated good or bad prognosis. Samples of each tumor group were selected and examined by immunohistochemistry using mAbs, raised against integrin chains (beta 1, beta 4, alpha 2, alpha 3, alpha 6) and their ligands laminin 1 and 5, collagen type IV, two fibronectin isoforms (ED-A and ED-B) and two isoforms of tenascin known to be associated with neoplasm. Controls were provided by samples of tumor-free laryngeal mucosa removed during the surgical procedure. The normal topographical integrin pattern and the continuity of the basement membrane components was altered in both groups but the extent of these changes was significantly greater in those tumors with poor prognosis. Therefore, the groups could easily and reliably be distinguished by simply observing their immunohistochemical features. It is suggested that performing immunohistochemical analysis on biopsies may aid in early diagnosis as well as in adopting the proper therapeutic strategy to follow for these tumors. The above molecules may become one of the diagnostic tools available for head and neck surgical pathologists.

Are recurrent and chronic tonsillitis different entities? An immunological study with specific markers of inflammatory stages.

It seems that there are clinical differences between tonsillitis in children and adults. In order to verify whether such a supposed clinical subdivision be true, tonsillar mononuclear cells from 20 children operated on for recurrent tonsillitis caused by a common flora and 20 adult patients with an indication for surgery for chronic tonsillitis were studied by means of monoclonal antibodies (MoAbs) specific for the antigens associated with each stage of the inflammatory response. BMA 4D10 and BMA 27E10 MoAbs were used as markers for the early stages, BMA RM 3/1 for the intermediate stage. BMA 25 F 9 for the late stage, and BMA G 16/1 for the chronic stage. The results indicate that chronic tonsillitis in the adult should be considered as such (higher expression of antigens associated with the chronic stages (p = 0.039), low and even lower expression of those associated with the intermediate and acute stages, respectively), whereas tonsillitis in children could perhaps be more correctly regarded as an expression of recurrent inflammation (higher expression of antigens associated with the acute stages (p = 0.022)). Results are presented and discussed.

[Recurrence after radiotherapy and/or surgery of carcinoma of the oropharynx and the pharynx. Possibilities of salvage surgery]. / Le recidive dopo radioterapia e/o chirurgia dei carcinomi dell'orofaringe e della laringe. Possibilità di recupero con chirurgia.

Forty-seven laryngeal and 21 oropharyngeal recurrences were treated with salvage surgery alone or combined with radiotherapy at the ENT Clinic and Radiotherapy Division of the University of Turin, Italy. Primary tumors had been treated with surgery alone in 10 cases (larynx) and in 21 cases (oropharynx), with combined surgery and radiotherapy in 2 and 8 patients, and with radiotherapy alone in 9 and 18 cases. We observed 26/47 (larynx) and 12/21 (oropharynx) recurrences at the site of primary tumor, 20/47 and 9/21 in loco-regional nodes, and 9/47 and 3/21 in locations adjacent to the primary tumor. Salvage treatment employed surgery alone in 12 (oropharynx) and 16 (larynx) cases; radiotherapy was combined in 9 and 31 cases. Five-year actuarial NED survival was 45.5% for laryngeal and 24% for oropharyngeal cancer patients. After salvage surgery, 50% of laryngeal lesions and only 25% of oropharyngeal recurrences were completely cured. In our series, in 2 cases only the complications caused the patient's death, while in the extant cases a prolonged postoperative hospitalization was necessary. Our study was aimed at investigating the curative potentials of secondary therapy for recurrent carcinomas. A review of the literature on the subject is reported. The small amount of published data prevents "universal" treatment protocol from being assessed. The authors suggest the opportunity of employing a multimodal treatment policy for recurrences of head and neck cancers.

[Prognostic significance of macrophage infiltration in laryngeal carcinoma]. / Significato prognostico dell'infiltrato macrofagico nel carcinoma laringeo.

We investigated the relationships between tumor associated macrofages (TAM) and tumor tissues and their possible prognostic significance in a laringeal carcinomas of patients operated in our Department for sovraglottic or total laringectomy. In our analysis we found a positive trend in Grade 3, but we could not find any correlations in the other cases. That shows that TAM have antithetic activities in the life of neoplasia.