Pulmonary resection for metastatic laryngeal carcinoma.

In a 5 year period, 11 patients were referred to our department as candidates for resection of pulmonary metastases from laryngeal carcinoma. At thoracotomy, a second primary tumor of the lung was discovered in three patients (27%). The other eight were considered eligible for thoracotomy and were subsequently proved to have metastases. Two of these patients (Group I) refused surgical treatment and died after 10 and 12 months; histologic diagnosis was obtained at autopsy. Six patients (Group II) underwent curative resection: Two of them have died (26 and 34 months) and four are alive and free of disease 40, 43, 46, and 55 months after thoracotomy. The disease-free interval, stage of primary tumor at laryngectomy, and single versus multiple metastases do not seem to affect survival. We conclude that lung resection increases survival in patients with pulmonary metastases from laryngeal carcinoma.

[Early diagnosis of pulmonary tumors in patients treated for laryngeal cancer]. / Diagnosi precoce di tumori polmonari in pazienti trattati per cancro laringeo.

Multiple primary malignant neoplasms occur relatively frequently today and are quite important. If the primary tumor ("index tumor") develops in the upper aero-digestive tract, the incidence of these neoplasms ranges from 10 to 20%, especially in males. The most common second primary site is again in the upper aero-digestive tract and, less frequently, in the lungs or thoracic esophagus. Among head and neck tumors laryngeal cancer is certainly one of the neoplasms most often playing the role of index tumor in association with malignant cephalic and extracephalic tumors. Among the most frequent associations of multiple primary malignant tumors one finds: larynx-lung and larynx-esophagus. As a high incidence of metachronous primary pulmonary cancers were observed during follow-up of patients who had undergone laryngeal surgery, a preventive flexible bronchofiberscope study was performed in 101 patients who had undergone surgery for laryngeal cancer over the ten years period from 1978 to 1987. The patients had a median age of 58.7 years (range 42-81) and were prevalently males (98 males, 3 females). The incidence of second primary neoplasm in the lung was 3%. During this bronchoscopic study the chest x-ray for 2 of the 3 patients with second primary neoplasm in the lung was normal, all 3 had an evident familiar neoplastic predisposition, one had been treated for colon carcinoma prior to laryngectomy. The authors report some personal opinions regarding the larynx-lung neoplastic association and emphasize the application of bronchoscopy in following-up laryngeal cancer patients.

[Association of primary malignant neoplasms of the larynx and the lung. 12 years of clinical experience]. / Associazione di neoplasie maligne primitive della laringe e del polmone. 12 anni di esperienza clinica.

Laryngeal and pulmonary cancers present a certain agreement in regard to annual incidence. When studied separately these tumors show certain similarities and differences and they are of particular interest when they arise in the same subject. The association of laryngeal and pulmonary neoplasms is one of the most common associations among multiple primitive malignant tumors and represents an important problem in terms of prevention and diagnosis. The present study involves 18 cases of associated tumors observed from January 1, 1977 and December 31, 1988. All the subjects involved were males, average age 62 years, who had been treated for laryngeal cancers, mostly laryngeal epidermoid carcinoma. Pulmonary cancers (simultaneous, synchronous, metachronous) were diagnosed in all these subjects and one patient presented 2 autonomous bronchial lesions which arose in different periods. On the whole, 8 out of 18 patients (44.4%) are still alive and of these 6 (33%) enjoy good health more than 1 year after treatment for the pulmonary tumor. After reporting some considerations regarding the neoplastic association between the larynx and the lungs and about the increased risk of pulmonary neoplasm in those patients treated for supraglottic lesions, the authors hypothesize that these neoplasms are simultaneously present in both organs more frequently than previously thought. The authors assert that laryngeal tumor patients must be considered as a potential carrier of pulmonary cancer. Therefore, both before and after treatment (particularly in the first 6 months after surgery and/or radiotherapy) the patient must be carefully observed.

A sensitive gas chromatographic assay for the determination of serum viloxazine concentration using a nitrogen-phosphorus-selective detector.

A gas-liquid chromatographic procedure for measuring the serum levels of the antidepressant viloxazine is described. The drug and the internal standard [imipramine (IMI)] are extracted from 1 ml serum. The method involves a three-step extraction, derivatization of viloxazine with acetic anhydride, and injection into a gas chromatograph equipped with a nitrogen-phosphorus-selective detector. The retention times for IMI and viloxazine were 4.7 and 6.1 min, respectively. The standard curves were linear over the 100- to 2,000-ng/ml range. The recovery averaged 64.5% and the lowest detection limit was 80 ng/ml. The within-run and day-to-day coefficients of variations were 11.9 and 12.5%, respectively, at 250 ng/ml, and 8.9 and 9.2%, respectively, at 1,500 ng/ml. The method is adequate both for single-dose pharmacokinetic studies and for monitoring serum viloxazine levels in chronically treated patients.

Increased dipropylacetic acid bioavailability from dipropylacetamide by food.

The present study was designed to investigate the influence of food on dipropylacetic acid (DPA) absorption from dipropylacetamide (DPM). Six healthy male volunteers received at weekly intervals, in a crossover randomized fashion, a single oral dose of 60 mg DPM, as 2 X 300-mg capsules, in a fasting state and after a standard meal. In the latter state, the lag time of DPA appearance in the serum increased significantly (p less than 0.02) from 0.6 +/- 0.2 to 2.3 +/- 1.2 h (mean values +/- SD). Maximal DPA serum levels and bioavailability increased significantly (p less than 0.05), with mean values of 27.7 +/- 19.8 and 19.0 +/- 14.7%, respectively, following food. The slower gastric emptying with a consequent improved DPM exposure to metabolizing enzymes and changes in gastric pH probably accounted for these findings. These results suggest that it is more advantageous to take DPM after meals. This helps to reduce gastrointestinal disturbances and to promote DPA absorption.

Single-dose kinetics of primidone in acute viral hepatitis.

The pharmacokinetics of primidone (PRM) after oral administration of a single 500 mg dose was studied in 7 patients with acute viral hepatitis and 7 healthy control subjects. The elimination half-life and the apparent clearance of unchanged PRM in the patients were 18.0 +/- 3.1 h and 42 +/- 14 ml X h-1 X kg-1, respectively (mean +/- SD) and did not differ significantly from the values in the controls (half-life 17.0 +/- 2.4 h; clearance 35 +/- 8 ml X h-1 X kg-1). The metabolite phenylethylmalonamide (PEMA) was detected in the serum of all normal subjects within 2-24 h. By contrast, serum levels of this metabolite were undetectable (less than 2 mumol/1) in all but one of the patients. Serum levels of phenobarbital (PB) remained below the limit of detection (less than 2 mumol/1) in all subjects. The findings indicate that accumulation of PRM with its attendant toxicity is unlikely to occur in epileptic patients who develop acute viral hepatitis, despite evidence that the metabolism of the drug is affected by this condition. The possibility of impaired conversion to PB and its implications are discussed.

Effect of viloxazine on serum carbamazepine levels in epileptic patients.

The present study describes the interaction between carbamazepine (CBZ) and viloxazine, a recently synthesized antidepressant agent. Seven epileptic patients on chronic anticonvulsant therapy showed a significant (p less than 0.005) increase in steady-state serum CBZ levels (from 8.1 +/- 2.5 SD to 12.1 +/- 2.5 SD micrograms/ml) when viloxazine (300 mg/day) was added to the therapy. The effect was associated with the appearance of mild CBZ intoxication. The symptoms of this intoxication (i.e., dizziness, ataxia, fatigue, drowsiness) disappeared rapidly, and serum CBZ levels decreased to the basal values, when viloxazine administration was stopped.