Fausto Chiesa

Fine-needle aspiration of parotid masses

Background. There is controversy concerning the utility of fine‐needle aspiration in diagnosing parotid masses. Even studies on large series of patients have compared aspiration findings with the histology in much fewer cases.

Prevention of local relapses and new localisations of oral leukoplakias with the synthetic retinoid fenretinide (4-HPR). Preliminary results.

This paper analyses preliminary results of a randomised chemoprevention trial in patients surgically treated for oral leukoplakia started in 1988 at the Istituto Nazionale Tumori of Milan with the synthetic retinoid N-(4-hydroxyphenyl)-retinamide (4-HPR). To date 115 patients have been randomised, after surgical excision of oral leukoplakia, to receive 200 mg 4-HPR daily for 52 weeks versus no intervention. 80 patients completed the 1-year intervention, 41 in the control group and 39 in the 4-HPR group. During this period 12 local relapses or new lesions occurred in the control group and three in the 4-HPR group. Only 5 patients interrupted the intervention because of toxicity. No impaired dark adaptation was observed. It is concluded that 4-HPR is well tolerated and seems efficacious in preventing relapses and new localisations during the treatment period. This promising trend needs further confirmation.

Successful topical treatment of oral lichen planus and leukoplakias with fenretinide (4-HPR)

Eight patients with diffuse (non-operable) pre-cancerous lesions (oral lichen or leukoplakias) were treated with fenretinidec (4-HPR) applied topically twice daily. After one month of therapy two patients had complete remission and the other six had a greater than 75% response. 4-HPR was well tolerated, and no local or distant side effects were observed. Topical treatment may be combined with oral administration at lower doses to obtain therapeutic results with less toxicity than observed with oral administration alone. A study to further evaluate the efficacy of topical treatment is in progress at our institute.

Randomized trial of fenretinide (4-HPR) to prevent recurrences, new localizations and carcinomas in patients operated on for oral leukoplakia : Long-term results

We assessed the efficacy of fenretinide at preventing relapses, new lesions and carcinomas after surgical excision of oral leukoplakia. In a controlled multicenter study, 170 patients operated on for oral leukoplakias with benign postoperative histology were randomized to 200 mg fenretinide daily for 1 year vs. no intervention. Preliminary analysis indicated that fenretinide had good tolerability and was effective at preventing relapses and new lesions during treatment. Analysis after 5‐year follow‐up suggested that fenretinide protected against relapses and new lesions up to 19 months after randomization, with both limits of the 95% hazard ratio CI for fenretinide vs. control below 1 for 7 months after randomization. There was also a protective effect against all first events, including cancer, for 25 months, with both limits of the 95% CI below 1 up to 11 months after randomization. Subsequently, risk ratio estimates were unstable. Fenretinide was well tolerated and effective at preventing relapses and new leukoplakias during treatment and after. The trial had to be stopped prematurely for very low recruitment and had insufficient power to reveal any protective effect against oral carcinoma; nevertheless, continuing studies on this promising chemopreventive are justified.

Laser Surgery for Early Glottic Cancer Impact of Margin Status on Local Control and Organ Preservation

OBJECTIVE To assess the impact of margin status on disease-free survival, overall survival, and organ preservation in early glottic cancer treated by endoscopic laser surgery. DESIGN Prospective nonrandomized study. SETTING Tertiary referral center. PATIENTS A total of 274 patients with untreated (possibly biopsied) cTis, cT1a/b, cT2, cN0 glottic cancer; adequate exposure of the glottic region; no contraindications to general anesthesia; and the ability to give informed consent. INTERVENTIONS European Laryngological Society laser cordectomy. Patients with negative margins (>1 mm) were followed, patients with close margins (< or =1 mm) or 1 positive margin (tumor on margin) had another operation, and patients with more than 1 positive margin had postoperative radiotherapy. Median follow-up was 58 months. MAIN OUTCOME MEASURES Eight-year disease-free survival, 5-year overall survival, and organ preservation rate. RESULTS Margins were negative in 180 patients, close in 40, and positive in 54. A second laser resection was performed in 36 of 94 patients with close or positive margins. Radiotherapy was administered to 36 patients. Patients with close or positive margins who did not undergo further treatment had a greater recurrence risk (hazard ratio, 2.53; 95% confidence interval, 0.97-6.59, P = .06) than did those with negative margins, mainly owing to relapses in 5 of the 8 protocol breakers with positive margins not treated further. Eight-year relapse-free survival was 88.2%, 5-year overall survival was 90.9%, and the larynx was preserved in 97.1%. CONCLUSIONS Laser removal of early glottic cancer is oncologically adequate with margins greater than 1 mm from the tumor edge. Positive margins require further treatment; close margins may require further treatment depending on tumor characteristics.

Swallowing dysfunction in head and neck cancer patients treated by radiotherapy: Review and recommendations of the supportive task group of the Italian Association of Radiation Oncology

PURPOSE Dysphagia is a debilitating complication in head and neck cancer patients (HNCPs) that may cause a high mortality rate for aspiration pneumonia. The aims of this paper were to summarize the normal swallowing mechanism focusing on its anatomo-physiology, to review the relevant literature in order to identify the main causes of dysphagia in HNCPs and to develop recommendations to be adopted for radiation oncology patients. The chemotherapy and surgery considerations on this topic were reported in recommendations only when they were supposed to increase the adverse effects of radiotherapy on dysphagia. MATERIALS AND METHODS The review of literature was focused on studies reporting dysphagia as a pre-treatment evaluation and as cancer and cancer therapy related side-effects, respectively. Relevant literature through the primary literature search and by articles identified in references was considered. The members of the group discussed the results and elaborated recommendations according to the Oxford CRBM levels of evidence and recommendations. The recommendations were revised by external Radiation Oncology, Ear Nose and Throat (ENT), Medical Oncology and Speech Language Pathology (SLP) experts. RESULTS Recommendations on pre-treatment assessment and on patients submitted to radiotherapy were given. The effects of concurrent therapies (i.e. surgery or chemotherapy) were taken into account. CONCLUSIONS In HNCPs treatment, disease control has to be considered in tandem with functional impact on swallowing function. SLPs should be included in a multidisciplinary approach to head and neck cancer.

European school of oncology advisory report to the European Commission for the Europe against cancer programme: Oral carcinogenesis in Europe

A European School of Oncology Advisory Group has reviewed current knowledge on the epidemiology, treatment and prevention of cancer of the oral cavity. While the major factors in the aetiology of such cancers are thought to be well understood, i.e. tobacco and alcohol consumption, current increases in the occurrence of the disease, especially in young adults throughout Europe, are cause for concern. The reasons for such increases are not clearly evident and the Advisory Group has suggested further work which is required to be carried out to understand the aetiology. In treatment of the disease there have been no major improvements in survival for patients in recent decades and the importance of examining new radiotherapy modalities and defining the role of chemotherapy is emphasized. Primary prevention of oral cancer could be achieved by stopping smoking tobacco, limiting alcohol consumption to a minimum (2-3 drinks per day) and increasing intake of fruits and vegetables. To supplement these actions, while neither population screening programmes nor screening trials could be recommended by the Advisory Group, initial chemoprevention trials have produced some promising results and this represents an interesting area which is the focus of much current research.

Risk of preneoplastic and neoplastic events in operated oral leukoplakias

We retrospectively analysed 167 consecutive patients with oral leukoplakias operated on by CO2 laser resection in the Day Hospital of the Istituto Nazionale Tumori in Milan from January 1981 to December 1988, with post-operative histological examination negative for cancer. Within 5 years there were 69 patients with at least one unfavourable event. First unfavourable events were: 31 local relapses, 27 new leukoplakias, 5 oral carcinomas and 6 other neoplasms elsewhere. To identify possible prognostic factors we recorded age, sex and history of previous oral leukoplakias or head and neck cancers; also number, site, size and type of lesion; as well as tobacco and alcohol consumption and oral hygiene. The Cox regression model was employed to compare disease-free survival between different patient groups, both by univariate and multivariate analysis. From this analysis it emerges that age of operated patients and size of resected lesion are significantly predictive for development of relapses, new leukoplakias and carcinomas.

Retrospective comparison of conservative and radical neck dissection in laryngeal cancer.

A retrospective comparison of radical and conservative technique for neck dissection in cancer of the larynx was made, starting from analysis of 98 patients operated on with the conservative procedure (128 cervical neck fields at risk of recurrence) at the Istituto Nazionale Tumori of Milan. Furthermore, a series of 162 patients was selected from more than 500 radical neck dissections performed in the past to set up a series as comparable as possible as far as several parameters were concerned. No significant difference was found between radical and conservative neck dissection with regard to the incidence of recurrences in the operative field, either considering the whole series (2.5% versus 1.6%), or cases with histologically proven metastases (9.4% versus 4.5%). Conservative neck dissection seems as safe as radical neck dissection, at least within the limits set in the present study for the indication of the former procedure, ie, nonsuspect nodes or metastatic mobile nodes not greater than 2.5 cm.

Excision of oral leukoplakias by CO2 laser on an out-patient basis: a useful procedure for prevention and early detection of oral carcinomas.

Several epidemiologic studies have shown that oral cancer develops among individuals with a prior diagnosis of an oral premalignant lesion. Canceration chance in these patients is 17 %, with the greatest rate occuring in the second year of observation. Based on this data, since 1981, 92 leucoplakias have been treated by out-patient laser surgery at the Istituto Nazionale Tumori of Milano. The therapeutic technique was laser excision to obtain a specimen for histology. Two groups were distinguished according to the diagnostic procedure. Thirtythree lesions (December 1981 to December 1982) were operated on without preliminary histologic examination, on the basis of a simple clinical diagnosis. Since January 1983 all leukoplakias have been biopsied in a systematic way and those negative for cancer treated with laser. Histology of the specimen showed 5 squamous cell carcinomas (15 %) in the group of patients who did not undergo preoperative biopsy. Postoperative histology showed malignancy in 6 of 59 (10.2 %) cases in spite of negative preoperative biopsies. Speckled and erosive leukoplakias had the highest canceration rate. Three of 11 patients with cancer were treated by knife excision or interstitial needle implantation because of margins in tumoral tissue or because they were unvaluable for injury by heat. Results have been satisfactory, only 2 of 54 followed leukoplakias and none of the cancers recurred during a 2 year follow-up.