The relation between cancer incidence among relatives and the occurrence of multiple primary carcinomas following head and neck cancer.

Despite improvement in therapeutic modalities in head and neck squamous cell carcinoma (HNSCC) the overall survival rate has only marginally improved during the last decades. The occurrence of second primary tumors (SPTs) in the respiratory and upper digestive tract (RUDT) is the main cause of treatment failure in early stage HNSCC. Identification of risk factors for the development of SPT by epidemiological analysis may lead to better risk assessment in individual cases. Ninety-seven HNSCC patients who ultimately developed SPTs and 100 HNSCC patients who remained free of other carcinomas after treatment of the first for a minimal period of 6 years were interviewed about the incidence of RUDT carcinomas within parents and siblings. All questioned patients were smokers. Among the SPT-positive patients, 50 (8.9%) of the 562 family members were reported to have had cancer of the respiratory or upper digestive tract versus 16 (2.5%) of the 629 family members of the SPT-negative patients. This difference was statistically significant (P < 0.0001) with the stratified version of Fisher's exact test. All these 66 probands with RUDT cancer were smokers, and the percentages of smokers were similar in both proband groups. Neither age and sex of the patient, nor tumor stage influenced the occurrence of SPTs in this study. The percentages of probands with tumors outside the RUDTs were almost similar, 8.0 and 7.0% in the SPT-positive and -negative groups, respectively. Having one or more relatives with RUDT cancer was established as a risk factor (odds ratio, 3.8; 95% confidence interval, 2.0-7.6) for patients with initial HNSCC to develop an SPT. These findings suggest that, in addition to external carcinogens, an intrinsic susceptibility may influence the risk for the development of SPTs in HNSCC patients.

Lack of effect of daily N-acetylcysteine supplementation on mutagen sensitivity.

The European Organization for Research and Treatment of Cancer multicenter Euroscan trial was set up to prevent the occurrence of second primary tumors in the upper aerodigestive and respiratory tract in patients cured for early stage head and neck squamous cell carcinoma. One randomized group of patients receive daily N-acetylcysteine, an antioxidant that may be protective especially in the early steps of carcinogenesis. Mutagen sensitivity, measured as sensitivity to bleomycin in peripheral blood lymphocytes, has been found to be increased in head and neck squamous cell carcinoma and is hypothesized to reflect cancer susceptibility. The aim of this study was to investigate whether mutagen sensitivity is influenced by oral N-acetylcysteine supplementation and can therefore be used as intermediate end point in chemoprevention. Patients (n = 19) who had various periods of N-acetylcysteine supplementation (600 mg daily for 3-9 months) were analyzed. In addition, a patient group (n = 14) that did not receive N-acetylcysteine supplementation was analyzed for comparison. Our results show no evidence that administration of N-acetylcysteine did influence the mutagen sensitivity level. The only explanatory variable in the analysis of the difference between two samples of one person was the b/c value of the first measurement. Moreover, the variability in these repeated measurements (coefficient of variation of 14%) indicates that additional studies should be performed to minimize this variability and to optimize the testing of mutagen sensitivity to accurately identify individual patients at high risk for the development of multiple primary tumors.

The value of twice yearly bronchoscopy in the work-up and follow-up of patients with laryngeal cancer.

The aim of this retrospective study was to investigate the usefulness and feasibility of twice-yearly bronchoscopy and sputum cytology in patients with laryngeal cancer. In 170 selected patients, 500 (both initial and during follow-up) bronchoscopies were performed. There was a maximum follow-up of 34 months. 5 (2.8%) male patients developed lung cancer. In only 2 of them was the diagnosis based on bronchoscopy alone. After treatment with curative intent, both patients developed a recurrent lung carcinoma. According to most patients' experience, regular bronchoscopy is unpleasant. It is concluded that twice-yearly bronchoscopy and sputum cytology in patients with laryngeal cancer is not useful as a routine procedure. At present, chemoprevention of second primary tumours seems the most promising adjunctive treatment modality.

Quantitative morphometry of squamous cell hyperplasia of the larynx.

The histopathological diagnosis of squamous cell hyperplasia of the larynx is very subjective. Since morphometry is highly reproducible, this method was applied to routine processed slides of 45 such lesions to assess objectively the epithelial characteristics. In each case measurements of nuclei of 50 cells in the basal, intermediate, and superficial cell layers were carried out. The data were analysed statistically. The findings suggest that quantitative morphometry may be helpful for the histopathological classification of squamous cell hyperplasia of the laryngeal mucosa.

Vocal cord paralysis and tumour length in staging postcricoid cancer.

The present UICC classification of postcricoid cancer is based on directions of tumour spread which are uncommon and difficult to assess clinically. The classification takes no note of spread into the cervical oesophagus and fails to correlate staging with survival. The aim of this study was to assess the value of other criteria, including vocal cord paralysis and tumour length, in staging 157 patients with postcricoid cancer. Both vocal cord paralysis and tumour length could be assessed in most patients, and correlated with the mode of treatment. Generalized Linear Interactive Modelling (GLIM) identified vocal cord paralysis (P less than 0.001), performance status (P less than 0.025) and the interaction of length and histological grade (P less than 0.05) as significant predictors of survival. None of these variables is included in the current UICC classification.

Spindle-cell carcinoma of the oral cavity and larynx. Immunohistochemical aspects.

Five cases of monophasic and 7 cases of biphasic spindle-cell carcinomas were analyzed immunohistochemically for the presence of vimentin and keratin type intermediate filaments in the pleomorphic spindle cells. Vimentin reactivity proved to be a consistent feature but keratin reactivity was more variable, this latter filament being lost in two cases initially presenting as pure squamous cell carcinomas showing dedifferentiation towards a pure monophasic spindle-cell tumour when recurring. The converse was also noted: acquisition of keratin in a monophasic spindle-cell tumour that recurred as squamous cell carcinoma. These results were considered to support the concept that spindle-cell tumours of the upper aerodigestive tract are a peculiar type of carcinoma and not a product of a pluripotent stem cell exhibiting bidirectional differentiation. Diagnostic implications are as follows: keratin positivity in a spindle-cell tumour substantiates its carcinomatous nature but its absence does not rule out a diagnosis of spindle-cell carcinoma.

Clinical implications of laryngeal amyloidosis.

Four cases of laryngeal amyloidosis are reported. For the present three of these cases have to be considered as primary localized amyloidosis, the type usually found in the larynx. Amyloid in the larynx may be a manifestation of the generalized or secondary form, which has to be excluded in each case. Diagnosis is provided by various histochemical stainings of which Congo red is the most specific one. Electron microscopy can be very helpful. Treatment consists of local excision. Recurrence may become manifest after several years and long-term follow-up is recommended.

Squamous cell hyperplasia of the larynx (a clinical follow-up study).

According to Kleinsasser's classification 200 patients with squamous cell hyperplasia, seen between 1963-1981, were reviewed histologically. The untreated patients (47 per cent) have been analysed for the incidence of malignant change and the patients with Class III lesions (carcinoma in situ) who were treated, were analysed for response to treatment. The mean follow-up period was 8.4 years. Only two of the 38 initially untreated patients of Class I (simple squamous cell hyperplasia) developed an invasive carcinoma. In Class II (hyperplasia with atypia), of 62 patients who were not treated initially, 17 developed a laryngeal squamous cell carcinoma later. Only six patients of Class III did not receive any treatment initially, and one of these progressed to invasive carcinoma. Almost all other patients with carcinoma in situ (Class III) were irradiated. In these patients no evidence of local recurrence was found.

An inverted papilloma with intracranial extension.

Inverted papilloma can be found in the lateral wall of the nose, the ethmoidal sinus, the maxillary sinus, the sphenoidal sinus and the frontal sinus. To our knowledge there are no reports of papillomas with intracranial extension. This case report describes the history of a patient with long-standing inverted papillomas, which eventually grew intracranially. The treatment of this patient and the treatment of inverted papilloma in general are discussed.

Landmarks for parotid gland surgery.

Many surgical landmarks have been suggested to help the surgeon identify the facial nerve when performing parotid gland surgery. There is no conclusive evidence that any one landmark is better than the rest. In this study distances from the most frequently used surgical landmarks to the main trunk of the facial nerve were measured in 30 halves of cadaver heads. Two ENT surgeons assessed the best landmark in each case. The tympanomastoid suture was nearest to the main trunk and was therefore considered the most reliable landmark. Its average distance to the main trunk of the facial nerve was 2.7 mm. This result was consistent with the subjective best score given by two ENT surgeons.

[Annual chest X-ray in patients after treatment for laryngeal or oral cancer: only a limited number of second primary lung cancers detected]. / Jaarlijkse thoraxfoto bij patiënten na behandeling wegens een larynx- of een mondholtecarcinoom: slechts beperkt rendement ten aanzien van tweede primaire tumoren in de long.

OBJECTIVE: To evaluate the detection of second primary lung cancer in patients treated for laryngeal or oral cancer by means of the current annual chest radiography screening program. DESIGN: Retrospective follow-up. METHOD: In a source population of Utrecht University Hospital consisting of patients treated for laryngeal or oral cancer, the occurrence of non-simultaneous second primary lung cancer was analysed. The charts of the patients who developed second primary lung cancer were reviewed with respect to diagnosis (either by means of routine annual chest radiography or triggered by symptoms and signs) and treatment of lung cancer. A Kaplan-Meier survival analysis was performed for both routes of diagnosis and for each form of lung cancer treatment. RESULTS: The source population consisted of 2067 patients. Second primary lung cancer was diagnosed in 44 patients (37 with laryngeal and 7 with oral cancer). In 21 patients lung cancer was diagnosed by means of annual chest radiography (routine group). The remaining 23 patients presented with symptoms and signs (symptomatic group). In 13 patients, surgery with curative intent was performed. These patients had the best prognosis. Of the surgical cases, 12 out of 13 patients (27% of the total of 44) were in the routine group. Patients in the routine group had better survival than those in the symptomatic group. CONCLUSION: In view of the limited number of patients with second primary lung cancer and the small percentage of patients eligible for curative surgical treatment detected by annual radiography, screening in its present form is of little benefit.

Premalignant laryngeal lesions.

Premalignant laryngeal lesions are classified into three classes according to the degree of atypia present: class I mild dysplasia, class II moderate dysplasia and class III severe dysplasia and carcinoma in situ. The risk that a carcinoma may develop later increases in the successive classes. The lesions are almost exclusively localized on the vocal cords. It is mandatory to remove the whole lesion for histopathological examination. A close cooperation between pathologist and laryngologist is necessary. progress in the development of more subjective and reproducible methods of grading is being made. Patients with class I and class II lesions are merely followed after an excisional biopsy. There is not a single best treatment modality for class III lesions. Radiotherapy has proven to be effective. However, the concept of microsurgical removal of the complete lesion seems to enable a more conservative approach for this class as well.

Transsphenoidal microsurgery as primary treatment in 25 acromegalic patients: results and follow-up.

Twenty-five patients with acromegaly were treated by transsphenoidal microsurgery. Fourteen patients (56%) were considered cured according to the following criteria: a. basal plasma GH less than 10 mU/l; b. glucose suppressed plasma GH less than or equal to 4 mU/l, and c. disappearance of TRH responsiveness if present preoperatively. Thirteen of the cured patients were re-evaluated after a mean follow-up period of 3.5 years (range 1.5 to 5.5 years). At that time, basal plasma GH was still less than 10 mU/l and glucose suppressed plasma GH was still less than or equal to 4 mU/l in all patients, indicating the practical value of our criteria. The remaining 11 patients (44%) received additional treatment by external pituitary irradiation and bromocriptine. Owing to surgery, 5 patients (20%) developed partial or panhypopituitarism.

Salivary gland carcinoma: independent prognostic factors for locoregional control, distant metastases, and overall survival: results of the Dutch head and neck oncology cooperative group.

BACKGROUND: We analyzed the records of patients with malignant salivary gland tumors, as diagnosed in centers of the Dutch Head and Neck Oncology Cooperative Group, in search of independent prognostic factors for locoregional control, distant metastases, and overall survival. METHODS: In 565 patients, we analyzed general results and looked for the potential prognostic variables of age, sex, delay, clinical and pathologic T and N stage, site (332 parotid, 76 submandibular, 129 oral cavity, 28 pharynx/larynx), pain, facial weakness, clinical and pathologic skin involvement, histologic type (WHO 1972 classification), treatment, resection margins, spill, perineural and vascular invasion, number of neck nodes, and extranodal disease. The median follow-up period was 74 months; it was 99 months for patients who were alive on the last follow-up. RESULTS: The rates of local control, regional control, distant metastasis-free and overall survival after 10 years were, respectively, 78%, 87%, 67%, and 50%. In multivariable analysis, local control was predicted by clinical T-stage, bone invasion, site, resection margin, and treatment. Regional control depended on N stage, facial nerve paralysis, and treatment. The relative risk with surgery alone, compared to surgery plus postoperative radiotherapy, was 9.7 for local recurrence and 2.3 for regional recurrence. Distant metastases were independently correlated with T and N stage, sex, perineural invasion, histologic type, and clinical skin involvement. Overall survival depended on age, sex, T and pN stage, site, skin and bone invasion. CONCLUSIONS: Several prognostic factors for locoregional control, distant metastases, and overall survival were found. Postoperative radiotherapy was found to improve locoregional control.

A nationwide study of the epidemiology, treatment and survival of oropharyngeal carcinoma in The Netherlands.

Seven head and neck oncology cooperative groups in the Netherlands have reviewed the epidemiology, staging, treatment and survival of oropharyngeal carcinoma patients treated between 1986 and 1990. In all, 640 patients with squamous cell carcinoma (628, 98%) or undifferentiated carcinoma (12, 2%) referred for primary treatment were analyzed. The total group included 441 males (69%) and 199 females (31%), with a median age of 59 years (range, 30-92). Tumor distribution by subsite was the tonsillar region (372 patients, 58%), base of the tongue/vallecula (179, 28%), soft palate/uvula (62, 10%) and posterior oropharyngeal wall (27, 4%). Forty-four patients (7%) had stage I disease, 106 (17%) had stage II disease, 157 (24%) stage III, and 319 (50%) stage IV. Staging was unknown in 14 patients (2%). Radiotherapy was given to the primary tumor in 408 patients (64%), surgery and radiotherapy to 147 (23%), surgery alone to 42 (7%), other treatments to 14 (2%) and no treatment to 29 patients (4%). The 5-year overall survival was 28% and the 5-year disease-specific survival was 41%. This latter survival was 35% in males and 51% in females (P = 0.003). Five-year survival by subsite was 54% in the soft palate/uvula, 42% in the tonsillar region, 33% in the base of the tongue and 32% in the posterior oropharyngeal wall (P = 0.003). When analyzing survival by stage, 5-year survival in patients with stage I disease was 68% and decreased significantly to 27% in stage IV disease (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)