In vivo cell kinetics in head and neck squamous cell carcinomas predicts local control and helps guide radiotherapy regimen.

PURPOSE: To determine whether pretherapy cell kinetics can predict local control for patients affected by head and neck squamous cell carcinomas (HN-SCCs) to be treated by primary radiotherapy and, moreover, guide to a choice between conventional and accelerated radiotherapy. PATIENTS AND METHODS: Between 1989 and 1993, 83 patients with stage II to IV HN-SCC entered the study. Multiple primary tumor biopsies were obtained 6 hours after in vivo infusion of bromodeoxyuridine (BrdUrd). In vivo S-phase fraction labeling index (LI), duration of S phase (Ts), and potential doubling time (Tpot) were obtained by analysis of multivariate flow-cytometric data. Between April 1989 and January 1991, 49 patients were treated by conventional radiotherapy (70 Gy in 35 fractions over 7 weeks), whereas, afterwards, 34 patients entered an accelerated radiotherapy regimen with the concomitant boost technique (75 Gy in 40 fractions over 6 weeks). RESULTS: Univariate analysis showed that, among patients treated by conventional radiotherapy, local control probability was affected by tumor stage (P = .02), Tpot (P < .001), and LI (P = .04). Similarly, among patients treated with accelerated radiotherapy, we found that local control probability was related to tumor stage (P = .03) and primary tumor site (P = .05). For the subgroup of patients with tumors characterized by fast growth (Tpot < or = 5 days), accelerated radiotherapy gave a better local control rate than conventional radiotherapy (P = .02). Cox multivariate analysis of the total number of patients showed that the only significant independent prognostic factors related to local control were tumor stage (P = .002) and Tpot (P = .004). Moreover, when the Cox analysis was restricted to the subgroup of patients treated with conventional radiotherapy, Tpot was the most significant factor to predict local outcome (P < .01). CONCLUSION: Pretreatment tumor Tpot appears to be an important independent prognostic factor for local control of HN-SCC treated by primary radiotherapy.

Antibiotic prophylaxis in ear, nose and throat surgery: a comparison of a single preoperative dose with three peri-operative doses of ceftazidime.

An open prospective randomized trial was conducted in three Italian ear, nose and throat (ENT) surgery departments on 120 patients aged 10 to 84 years, to compare a single pre-operative dose vs. three peri-operative doses of ceftazidime in surgical prophylaxis. Sixty patients in group I received 1 g ceftazidime intramuscularly (im) or intravenously (iv) 1 h before surgery, and 60 in group II received three 1 g doses of ceftazidime, im or iv, 1 h before, and 6 and 12 h after surgery. Post-operative infections were observed in six group I patients (10.1%) and seven group II patients (11.6%). All infections arose in patients who had undergone 'moderate-risk' (6.7%) or 'high-risk' surgery (30.5%). We conclude that a single pre-operative 1 g dose of ceftazidime is as efficacious as multiple peri-operative doses in the prophylaxis of infectious complications following this type of surgery.

Alternating cisplatin-5-fluorouracil and radiotherapy in head and neck cancer.

Thirty-four patients with advanced (stage IV) or relapsing squamous cell carcinoma of the head and neck (SCC-HN) were treated alternately with chemotherapy (CT) and radiotherapy (RT). Patients' characteristics were as follows: male: female ratio, 27:7; median age, 55 (34-76), median P.S., 1 (ECOG scale) (range 0-2). Patients studied had no renal, hepatic, or cardiac impairments, a life expectancy of greater than or equal to 3 months, and no previous treatment with RT or CT. Seventeen patients were previously untreated, and 17 had a relapse after radical surgery. The CT regimen consisted of 20 mg/m2 cisplatin, with 2 h forced diuresis, from day 1 to 5, and 200 mg/m2 i.v., from day 1 to 5, every 3 weeks, administered four times. The RT was performed after the first, second, and third CT course, and consisted of three courses of 20 Gy each, 2 Gy daily, 5 days per week. Weekend intervals were planned between CT and RT treatments. The 17 previously untreated patients showed an overall response rate of 88.2% [eight complete response (CR), seven partial response (PR), one stable disease (SD), one progression disease (PD)]; the 17 patients treated at relapse after radical surgery reached an overall response rate of 64.7% (six CR, five PR, six PD). Actuarial median survival is 47 weeks: 51 weeks in untreated patients, and 42 weeks in previously treated patients. Toxicity was mild, and only 10 patients suffered from grade III (WHO scale) gastrointestinal (2 patients), hematological (5 patients), mucosal (2 patients), and neurological (1 patient) toxicity. Neither grade IV toxicity nor treatment-related deaths have been observed. In our study, cisplatin and 5-FU alternating with RT has shown an interesting antitumor activity and moderate side effects.

Primary site as predictive factor of local control in advanced head and neck tumors treated by concomitant boost accelerated radiotherapy.

AIMS AND BACKGROUND: The purpose of this phase II study was to assess the efficacy and toxicity of an accelerated radiotherapy schedule with the concomitant boost technique in the management of patients with advanced head and neck squamous cell carcinomas (HN-SCC) of various primary sites. METHODS: From May 1989 to December 1992 45 patients were scheduled to receive a total dose of 75 Gy in 40 fractions over 40 days. The boost encompassing the macroscopic disease was given as a second daily dose during the last 2 weeks of the basic treatment. RESULTS: Severe mucositis was recorded in 27 (60%) patients. Late side effect occurred in 2. As regards local control the primary tumor site was the most significant prognostic factor: at a median follow-up of 24 months (range 12-52 months) the actuarial local control rate was 79%, 48% and 15% for oronasopharyngeal, laryngohypopharyngeal and oral cavity primary sites, respectively (p = 0.004). CONCLUSIONS: This high dose concomitant boost regimen appears feasible in advanced HN-SCC. However, our results indicate the primary tumor site as a major prognostic factor even with an accelerated treatment schedule.

Cell kinetics analysis in patients affected by squamous cell carcinoma of the head and neck treated with primary surgery and adjuvant radiotherapy.

BACKGROUND: The increasing complexity of management strategies for patients with head and neck squamous cell carcinoma (HN-SCC) calls for the investigation of new objective prognostic parameters to subdivide patients according to the tumor's biological aggressiveness. METHODS: We evaluated in 35 HN-SCC patients the pretreatment cell kinetics parameters and DNA ploidy after in vivo infusion of bromodeoxyuridine and flow cytometric analysis. Patients were treated with radical surgery followed by conventional radiation therapy. Locoregional control data are available for follow-up times above five years. RESULTS: We found that the likelihood of locoregional control for patients with rapidly proliferating HN-SCC characterized by a short potential doubling time (Tpot <5 days) was significantly smaller than for HN-SCC patients with slow tumor proliferation (Tpot >5 days). Moreover, when patients were stratified according to DNA ploidy and Tpot value, we found that the locoregional failure rate for rapidly proliferating tumors was significantly higher for diploid HN-SCCs than for aneuploid HN-SCCs. CONCLUSION: The present data suggest that patients with resectable HN-SCC characterized by fast growth might have a worse prognosis after surgery and adjuvant conventional radiotherapy and might benefit from more aggressive radiotherapeutic modalities.

[Labayle's supracricoid partial laryngectomy in the treatment of laryngeal cancer: personal experience and long term follow up]. / Laringectomia ricostruttiva sopracricoidea secondo Labayle: esperienze personali e valutazione di pazienti a prolungato follow-up.

The present study was carried out to assess the indications and to evaluate the functional and oncological results of the supracricoid laryngectomy with crico-hyoid-pexy proposed by J. Labayle. This technique consists of a sub-total laryngectomy where the cricoid cartilage, the hyoid bone and at least one of the arytenoids are spared. These structures can then be reassembled into a "neo-larynx", thus preserving respiration and phonation. The present paper deals with 23 laryngeal carcinomas: 13 glottic (2 T1bN0, 6 T2N0, 1 T2N1, 1 T2N1, 3 T3N0) and 10 supraglottic (4 T2N0, 3 T2N1, 3 T2N2). The follow-up shows a 5-year overall actuarial survival rate of 80.65%. The authors agree that when performed under very precise indications the crico-hyoid-pexy is a useful alternative to both radiotherapy and the extended-partial or total laryngectomy in the treatment of laryngeal carcinoma. It also appears useful in treating selected cases of post-surgical or post-radiotherapy recurrences.

[The interactions between metal stapes prostheses and high-intensity magnetic fields during magnetic resonance tomography]. / Interazioni tra protesi stapediali metalliche e campi magnetici di elevata intensità in corso di tomografia a risonanza magnetica.

The ever-increasing use of magnetic resonance tomography (MR) as an investigation mean has created a new interest in the biological effects of magnetic fields (MF) and in finding protective measures to be taken in their event. At the moment, use of MR is contraindicated in the presence of pacemakers, vascular clips, liquoral shunts and orthopedic prostheses, all of which may be dislocated by the MF created by MR or may interact with the MF itself creating distorted or falsified images. The aim of our study was to verify if metallic stapedectomy prostheses are dislocated by the MF and if they produce enough interference to falsify MR images. Five types of metallic stapedial prostheses exposed to a MF of 0.5T were studied. We may conclude from our results that MR does not create any otological risks for patients with these prostheses in that none of them were dislocated during exposure. However, all the prostheses studied did instead bring about alterations in the MF and the MR image to varying degrees. In some cases (Robinson) there was notable image distortion, while in others (Schuknecht wire teflon and platinum piston) the distortion was practically negligible. It is our opinion, however, that even if the image distortion does not interfere with routine MR, use of prostheses made of materials not affected by MF are advisable in view of an eventual development of visualization of the labyrinth and intratemporal facial nerve portion with MR.

Effect of repetition of Semont's manoeuvre on benign paroxysmal positional vertigo of posterior semicircular canal.

If Semont's liberating manoeuvre does not lead to relief of symptoms in benign paroxysmal positional vertigo of posterior semicircular canal after the first session, it can be repeated once again, in refractory cases, whilst symptomatic patients after second manoeuvre require rehabilitation therapy Repeating Semont's manoeuvre several times has proven to progressively increase the percentage of cured patients or it may convert posterior semicircular canal forms to typical incomplete or lateral semicircular canal forms, hence requiring other manoeuvres to achieve vertigo resolution. Aim of study was to assess the effect of liberating manoeuvres repeated up to 4 times and to establish possible passages from one canal to the other during manoeuvres as well as percentage of cases refractory to this therapy, who would then need rehabilitation. Benign paroxysmal positional vertigo was diagnosed in 448 cases of whom 344 (76.8%) of the posterior semicircular canal, 20 (0.45%) the incomplete form of the posterior semicircular canal, 20 (0.45%) subjective positional vertigo and 74 of the lateral semicircular canal (4.2%). Right side was affected in 58.4% of cases, left in 34.5%, and bilateral in 7.1%. All 344 patients underwent Semont's liberating manoeuvre (1st manoeuvre) with first control after 48 hours: if symptoms (typical, atypical nystagmus or paroxysmal vertigo evoked by Dix-Hallpike's manoeuvre) persisted, Semont's liberating manoeuvre was repeated (2nd manoeuvre). In presence of lateral semicircular canal benign paroxysmal positional vertigo conversion, Lempert's manoeuvre was performed instead. Second control was performed after 48 hours and in cases of persistent typical, atypical or lateral semicircular canal nystagmus 3rd manoeuvre was performed. After further 48 hours, third control was carried out: symptomatic patients with typical forms were submitted to 4th manoeuvre, while typical incomplete forms or forms of the lateral semicircular canal underwent Lempert's manoeuvre. In conclusion, symptoms disappeared after 1st manoeuvre in 61.6% of cases; further manoeuvres, carried out in view of possible changes in semeiology of vertigo, increased the percentage of cured patients to 82.5% after the 2nd, 90.7% after 3rd and 94.1% after the 4th. Repeated positioning manoeuvres in benign paroxysmal positional vertigo led to a progressive increase in percentage of cured vertigo, at the same time, allowing detection of those cases converted to multicanal pathology, hence offering the possibility to proceed with appropriate liberating manoeuvres.

[Combined genioglossus advancement (ACMG): inferior sagittal mandibular osteotomy with genioglossus advancement and stabilization with suture in patients with OSAS. Preliminary clinical results]. / Avanzamento combinato del muscolo genioglosso (ACMG): osteotomia infero-sagittale mandibolare con avanzamento muscolo genioglosso e sua stabilizzazione con sutura in pazienti con OSAS. Risultati clinici preliminari.

Surgical treatment of obstructive sleep apnea syndrome (OSAS) centres on the identification of the level of obstruction of the upper airway and the choice of the most suitable procedure to correct it. Shaping of the retrolingual hypopharyngeal space is among the most difficult to achieve because it stems from an alteration of the soft tissue of the tongue, from the hypopharynx, and is correlated to the contraction pattern of the genioglossus and the pharyngeal constrictors. We propose a surgical technique of combined genioglossus advancement (CGA) in cases of anteroposterior collapse of the retrolingual airway. Four patients affected by OSAS (RDI average = 22 events/hour), evaluated as type III obstruction in the Fujita classification, presenting the indications for surgical management of retrolingual hypopharingeal obstruction, underwent treatment. They were studied by means of a guided medical history, fiberopy endoscopy evaluation and Muller maneuver, cephalometry, endocrine tests, pneumological examinations and polysomnography. The technique proposed consists in the advancement of the genioglossus muscle by means of a bone screw on the mandibular symphysis, according to the method described by Powell, associated with the stabilization of the base of the tongue with a suspension suture, following the technique originally described by the Author and DeRowe, but without using the Repose kit. This technique makes it possible to access the retrolingual site of obstruction more effectively, more economically and with no increase in morbidity when compared with the individual techniques. In all of the patients, the only complaints regarded dysaesthesia in the area of the lower lip innerved by the mental nerve for 2-5 weeks and moderate odynophagia for 2-3 weeks; there were no haemorrhages or infections. Deglutition of fluids and solids was resumed on the 3rd post-operative day. Polysomnography after 6 months documented three positive results and one partial result, on the basis of Sher's criteria. In conclusion, the CGA technique calls for advancement of the genioglossus insertion tubercle and stabilization of the tongue to be carried out at the same time, without using the Repose kit. The CGA technique is minimally invasive and does not involve cutaneous incisions, making it a therapeutic strategy which may be inserted in a multilevel protocol excluding transcutaneous access. It is therefore proposed for type III or type IIb cases in the Fujita classification.

[Analysis of the cellular infiltrate and epithelial class I and II molecular expression in edematous type nasal polyps]. / Analisi dell'infiltrato cellulare e della espressione epiteliale di molecole HLA di istocompatibilitá di classe I e II in polipi naso-sinusali di tipo edematoso.

Although in the last few years histopathological, immunohistochemical and immunological studies on nasal polyps have been carried out by several Authors, the etiology of these formations still remains unknown. Nasal polyps have a very characteristic structure and have been classified in three histologic types: edematous, glandular and fibrous. In the present report, 11 nasal polyps of edematous type, representing 61% of total number of collected polyps, were studied employing immunohistochemical methods. All the examined polyps were similar in histology and positivity pattern for HLA molecule expression. The edematous core appeared infiltrated (149 cells/mm.2) mainly by eosinophils (> 90%), whereas the peripheral subepithelial connective tissue contained cellular clusters (416 cells/mm2.) made up of different subsets of hematic cells (30.8% were monocytes-macrophages and 48.6% were lymphocytes largely represented by CD4+ cells). On the contrary, mast cells were quite rare (on the average 1.7 cells/mm2.) and located near T cell clusters. The epithelial positivity for HLA-DR and HLA-A,B,C molecules showed a characteristic discontinuous pattern. In the same patient, controlateral nasal mucosa showed a histological structure very similar to that of polyps. The above data suggest that the presence of polyps is the result of an inflammatory process brought about by a complex array of cellular and humoral components.

[Nasal polyps: comparative immunological study of polyps with different histopathologic types]. / I polipi naso-sinusali: studio immunoistologico comparativo di formazioni con differente tipologia istopatologica.

Cellular Infiltrate as well as class I and II HLA molecule expression, on 22 nasal polyps and on 12 samples of corresponding hypsilateral mucous membrane were studied by means of immuno-histological methods. These nasal polyps were classified according to their histopathological structure. Five polyps, with a fibrous connective core infiltrated by cells of the monocyte-macrophage lineage, were classified mixed. The remaining seventeen polyps were characterized by the presence of central oedematous connective tissue infiltrated almost exclusively by eosinophils and either contained (glandular type) or did not contain (oedematous type) glands. A comparative study of different types of nasal polyps and corresponding hypsilateral nasal mucous membranes was carried out on atopic and non-atopic patients. No correlation between atopic status and polyp presence or polyp typology was found. On the other hand, different polyp types appear to have a structural correlation with the corresponding hypsilateral mucous membrane regarding infiltrate cell type, oedematous or fibrous connective tissue presence and expression of on HLA antigen positivity pattern. The characteristic histological structure of hypsilateral mucous membranes in patients with different types of polyps appeared to be brought about by a multifactorial etiology involving mucosal hyperreactivity. Lastly, both polyps and parapolypal nasal mucous membranes were found to be infiltrated mainly in the peripheral subepithelial connective tissue by lymphocytes (55%) as well as by other leukocyte types. The presence of growth factors capable of enhancing an increase of fibroblasts, endothelial cells, together with focal distrupture on the basal membrane, might well be a general mechanism responsible for polyp sprouting.

[Lymphoma of the Waldeyer's ring: experience at the National Institute for Cancer Research of Genoa]. / I linfomi del Waldeyer: esperienza dell'Istituto Nazionale per la Ricerca sul Cancro di Genova.

Malignant lymphomas account for 3% of all malignant disease in the head and neck area. Twenty-five to fifty percent of all lymphomas arising in this region develop in extra-nodal structures, mostly in the Waldeyer ring. Lymphomas of the Waldeyer ring are comparable to any other lymphomas and prognosis is strictly related to stage and histology. The present paper reports 51 patients with malignant lymphomas arising in the head and neck (25 patients with Waldeyer ring involvement) recorded at the National Institute for Cancer Research, Genoa, Italy, from 1985 to the present. The characteristics of patients with Waldeyer ring involvement are comparable to those reported in the literature. Differences can be found in the median age (older in the present series) and in the incidence of Hodgkin's disease (8%). Patients were treated according to stage: stage I and II received radiation therapy and, in a few selected patients, this was combined with chemotherapy; stage III-IV received chemotherapy followed, in a few selected patients, by radiation therapy. In the present series, survival was related to the involvement of the Waldeyer ring: analysis has shown that survival is better in those patients with only nodal involvement. Nevertheless, these patients usually have a more advanced stage (p = less than 0.03). This finding is quite surprising since all the known prognostic factors are better in the Waldeyer group.

Anterior clinoid mucocele: a trans-nasal endoscopic approach.

The goals of the treatment of paranasal sinuses mucocele are the relief of the symptoms due to compression and the prevention of recurrence. Because of the benignity of the pathology, it is mandatory to choose the approach that minimizes the surgical trauma. When an anterior clinoid mucocele is found, the conventional approaches are the trans-nasoethmoidal, the subtemporal or the pterional ones: we think that as a really mini-invasive approach, the transnasal endoscopy may be proposed. Anterior clinoid localization may be reached by a trans-sphenoidal way and treated by endoscopic microsurgery with a very low morbility. This paper deals with a case of anterior clinoid mucocele treated by this way with good anatomic and functional results and stresses the importance of the pre-operative imaging (CT/MR) allowing one to make a sure diagnosis and to choose the cases suitable for this surgical approach.

Decreased sensitivity of T lymphocytes to normal adherent suppressor cells in patients with head and neck cancer.

The sensitivity of T Lymphocytes to the inhibitory action of normal adherent cells in the mixed lymphocyte reaction (MLR) was studied in 20 subjects with head and neck cancer. T lymphocytes from cancer patients proliferated in the MLR both in the absence and in the presence of increasing numbers of autologous as well as allogeneic adherent cells, while the blastogenesis of T lymphocytes from controls was inhibited up to 70% by the addition of adherent cells to the culture. Such a lack of sensitivity to adherent cells in cancer patients occurred both in allogeneic and in autologous MLR. These observations indicate that the immunocompetence of patients with head and neck cancer may be related to a defect of macrophage-T lymphocyte interaction similar to the one described in patients with common varied immunodeficiency.

[Expression of HLA-DR, DP, DQ antigens in fibrous sino-nasal polyps]. / Espressione di antigeni HLA-DR, DP, DQ, in polipi naso-sinusali di tipo fibroso.

In the last years nasal polyps have been studied by several authors with different methodologies; however, their etiology is still unclear. In this paper we have analyzed in four nasal polyps of fibrous type, the HLA class II (HLA-DR, DP, DQ) molecule expression by means of immunohistochemical techniques (immunoperoxidase and immunophosphatase). A strong inflammatory cell infiltration, a percentage increase of both HLA-DR+ and HLA-DQ+ cells (normal nasal mucous membrane stroma infiltrating cells: DR+ < 40%, DP+ < 2%, DQ+ < 3%; fibrous polyps infiltrating cells: DR+ = 68%, DP+ < 2, DQ+ = 7%) as well as a clear positivity for DR expression of both surface and glandular epithelia were observed in all polyps. Furthermore, in the stalk area of one of the studied polyps DR+DQ+ cells with macrophagic features and having tight. connections with the vessels were observed. The scanty vascularization with the presence of activated mononuclear and mast cells might be responsible for polyp growth by locally producing an anomalous concentration of growth factors.

[Hematic infiltrates and the expression of HLA-DR antigens in naso-sinusoidal polyps of the fibrous type]. / L' infiltrato ematico e la espressione di antigeni HLA-DR in polipi naso-sinusali di tipo fibroso.

In this study fibrous nasal polyps, obtained from four patients, were analyzed by means of immunocytochemical methods for the presence of interstitial hematic cell infiltrate and HLA-DR molecule expression. This histologic type accounted for 36.4% of nasal polyps studied. Our results demonstrated that cells belonging to monocyte-macrophage lineage were mainly detected within fibrous and edematous zones (greater than 50%), whereas T cells were found within the subepithelial peripheral connective tissue (greater than 60%). Surface and gland epithelial cells appeared to be more intensely stained for HLA-DR molecules than nasal epithelium of normal subjects, thus indicating that the intensity of HLA-DR molecule expression correlated with the presence of a hematic cell infiltrate. Nasal polyps are a frequent pathology whose etiology has not yet been completely clarified. The present study provides additional information about the fibrous polyp structure and can support some speculations on the nasal polyp etiology.

Cell kinetics and tumor regression during radiotherapy in head and neck squamous-cell carcinomas.

Head and neck squamous-cell carcinoma (HN-SCC) patient management is mainly based on TNM classification and needs be improved by considering other potentially useful prognostic factors. We examined the pre-radiotherapy tumor potential doubling time (Tpot) evaluated after in vivo infusion of bromodeoxyuridine and flow-cytometric analysis and the early clinical tumor regression after 40 Gy (40 Gy-TR). Tpot values and clinical 40 Gy-TR classes (minor and major) were available for 82 HN-SCC patients. Radiation therapy completion was done either with 1 dose per day (conventional regimen) or 2 doses per day (accelerated regimen). Local control was also available for follow-up times above 4 years. We found that major 40 Gy-TR was strongly correlated with fast tumor growth, characterized by Tpot values below 5 days, and that patients with major 40 Gy-TR showed better local control than those with minor 40 Gy-TR, independently from the radiotherapy regimen type. We also found that treatment completion with accelerated radiotherapy gave better local control for patients with major 40 Gy-TR and fast tumor growth than conventional radiotherapy. Multivariate analysis, performed on all patients, assigned an independent prognostic value to Tpot, tumor classification and 40 Gy-TR.