Hyperfractionated radiation therapy and concurrent 5-fluorouracil, cisplatin and mitomycin-C in head and neck carcinoma. A pilot study.

Seventeen patients were entered into a Phase I/II trial of concurrent hyperfractionated radiation therapy (7,440 cGy total dose; 120 cGy b.i.d.) combined with constant infusion of 5-fluorouracil (5-FU) (1,000 mg/m2/24 hours for 72 hours) and cisplatin (DDP) (50 mg/m2) for a total of three cycles. Thirteen patients had Stage IV disease; three, Stage III disease; and one, Stage II hypopharyngeal disease. Thirteen of 17 patients had positive cervical lymph nodes, and the mean size of the largest lymph node was 5.5 x 5.1 cm. The patients were not treated with planned adjunctive surgery except for one patient who had a radical neck dissection for massive, rapidly growing cervical adenopathy, which recurred promptly within 1 month before the initiation of protocol therapy. After the initial six patients were entered, mitomycin-C (Mito 8 mg/m2) was added during the second cycle. All the patients completed the planned course of radiotherapy with a median dose of 7,440 cGy and a mean dose of 7,248 cGy except for two patients who died--one from toxicity and the other, suicide. The predominant toxicity was mucositis, which was grade 3/4 in 11 of 15 patients, resulting in an average interruption of radiation therapy of 12 days. Weight loss was significant and was on the average 12% of baseline weight. Hematological toxicity was mild in the 5-FU/DDP group (only one grade 3 toxicity of six) and severe in the 5-FU/DDP/Mito-treated patients (five of eight patients having grade 3/4 toxicity including one leukopenic pneumonitis death). Additional toxicity included one parapharyngeal cellulitis, which responded to antibiotics. Noncompliance with the complex regimen was only seen in three patients. One patient refused b.i.d. radiation therapy, and one patient refused further chemotherapy after the first cycle. Additionally, one patient who had a severe ethanol withdrawal reaction during the first cycle of 5-FU/DDP did not receive further chemotherapy. The complete response rate of both primary site and neck by the protocol regimen alone was 71%. However, two patients, one from each group, did undergo salvage neck dissection, and the locoregional control is currently 73%, with a mean follow-up time of 18.4 months. The feasibility of combining hyperfractionated radiation therapy with aggressive concurrent chemotherapy was demonstrated. The response and local control rate justifies the added toxicity of concurrent chemotherapy and radiation therapy.     

New strategies are needed in diffuse malignant mesothelioma.

BACKGROUND. Medical records of 50 patients with malignant mesothelioma were reviewed to determine the clinical features and factors influencing survival. METHODS. Charts of all patients whose conditions were diagnosed as malignant mesothelioma were abstracted and analyzed by statistical software. RESULTS. The male-to-female ratio was 4:1. The age distribution was younger than 45 years of age, 10%; 45-54 years of age, 12%; 55-64 years of age, 37%; 65-74 years of age, 33%; and 75 years of age or older, 8%. Both mean and median ages were 58 years. Among the 32 patients in whom asbestos exposure was recorded, 24 had documented exposure. The sites were pleura, 73%; peritoneum, 20%; and both, 6%. The histologic types were epithelial, 51%; sarcomatous, 10%; mixed, 15%; and not specified, 24%. The stage at presentation was Stage I, 37%; II, 39%; III, 12%; IV, 6%; and unknown, 6%. The common symptoms in pleural disease were dyspnea and pain; in peritoneal disease, abdominal distension and pain were common. The median time from first symptom to diagnosis was 3 months (range, 0-23 months). The median survival after the appearance of symptoms, the diagnosis, and the treatment were 13, 10, and 8 months, respectively. CONCLUSIONS. The survival was independent of age, sex, and smoking behavior. It was longer in patients with earlier-stage disease, a good performance status, a longer duration of symptoms, an absence of pain, and who were treated with combined surgery and chemotherapy. Chemotherapy using anthracyclines yielded more remissions (9 of 21) than that using nonanthracyclines (0 of 13). The remission rate after primary chemotherapy with anthracyclines (7 of 16) may be higher than in recurrent tumor (2 of 14). In future trials, stratification into primary chemotherapy and chemotherapy of recurrent cancer is suggested. There is a need for multitechnique trials incorporating primary chemotherapy.     

Spirometric indices of early airflow obstruction.

Thirty cigarette smokers and 25 non-smoking controls, all men were evaluated by history, physical examination and simple spirometry. The history and physical examination were not of much use in predicting airflow obstruction. Forced mid-expiratory flow (FEF 25-75%) was abnormally low in 23 of the 30 subjects, while forced expiratory volume in 1 second (FEV1) and FEV1/FVC (forced vital capacity) were less sensitive. Thus simple spirometry is a useful screening tool to detect early airflow obstruction even when it is clinically undetectable.     

Resting energy expenditure and nutritional state of patients with increased oxygen cost of breathing due to emphysema, scoliosis and thoracoplasty.

BACKGROUND--Weight loss is a well recognised feature of patients with emphysematous chronic obstructive pulmonary disease (COPD). It has been suggested that this weight loss could be due to a hypermetabolic state resulting from the increased oxygen cost of breathing (OCB). To clarify the relation between resting energy expenditure (REE), nutritional state, and OCB these indices were measured in patients with respiratory impairment and an increased OCB due to COPD, scoliosis, and thoracoplasty. METHODS--Eighteen patients (six COPD, six scoliosis, six thoracoplasty) of mean (SD) age 59.9 (8.6) years (8M, 10F) and six controls (45.5 (9.9) years; 2M, 4F) were studied. OCB was estimated by the addition of dead space to the breathing circuit and REE was measured by indirect calorimetry using a ventilated canopy system. Height, arm span, weight, triceps skin fold thickness (TSF), mid-arm muscle circumference (MAMC), forced expiratory volume in one second (FEV1), and vital capacity (VC) were measured in all study subjects. RESULTS--OCB was elevated in all patient groups (mean 7.0 ml/l) compared with controls (1.9 ml/l). All patients with COPD, four with scoliosis, three with thoracoplasty, and none of the controls were < 90% ideal body weight. Mean (SD) measured REE as % predicted (Harris-Benedict equation) was 103.8 (7.6) in patients with COPD, 105.5 (10.9) in those with scoliosis, 106.3 (6.9) in the thoracoplasty patients, and 103.3 (3.4) in controls. One patient with COPD, two with scoliosis, two with thoracoplasty, but no controls were hypermetabolic (REE > 110% predicted). In all groups there was a negative relation between OCB and lung function (OCB v FEV1 r = -0.83 in COPD, -0.62 in scoliosis, -0.67 in thoracoplasty, and -0.76 in controls). There was no correlation between REE and OCB or MAMC. CONCLUSIONS--In patients with respiratory disease OCB (augmented ventilation) is related to lung function but not to REE. This is evidence against the hypothesis that hypermetabolism due to increased oxygen cost of breathing at rest is the sole or major cause of malnutrition in patients with lung disease.     

Placental p,p''-dichlorodiphenyldichloroethylene and cord blood immune markers

Placental p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) concentration and cord blood atopic markers were determined in 19 neonates. Increased placental p,p'-DDE was associated with a statistically significant increase in cord plasma interleukin (IL)-13. Furthermore, both cord plasma IL-4/interferon (IFN)-gamma and IL-13/IFN-gamma ratios were significantly positively associated with placental p,p'-DDE concentration.     

The relationship of serum IL-6 levels to acute graft-versus-host disease and hepatorenal disease after human bone marrow transplantation.

The potential involvement of cytokines in acute graft-versus-host disease led us to analyze interleukin-6 in serial serum sets from 22 allogeneic marrow recipients who developed either grade 3 or 4 GVHD (n = 10), grade 2 GVHD (n = 6), or grade 1 or no diagnosed GVHD (n = 6). A total of 279 serial serum samples taken three times weekly before day 35 were analyzed. Maximum IL-6 levels were greater than 40 U/ml (range, 40-1536 U/ml), 11-40 U/ml, and less than or equal to 10 U/ml for six, eleven, and five patients, respectively. Serum IL-6 peaks were temporally related to onset of GVHD, onset of a syndrome of hepatorenal dysfunction (HRD), or bilateral lung infiltration. Eight of ten patients who developed grade 3 or 4 GVHD overall had IL-6 maxima of greater than 10 U/ml an average of 1.5 +/- 1.8 days before the clinical onset. Fifteen of 17 patients with peak IL-6 levels greater than 10 U/ml developed symptoms of hepatic and renal dysfunction within three days of the peak, while none of five patients with less than or equal to 10 U/ml of Il-6 developed HRD. Regression analysis demonstrated a linkage between the log magnitudes of the serum IL-6 peaks and onset of either GVHD or HRD within three days (P = 0.001). Furthermore, IL-6 peaks tended to precede GVHD onset for the 10 patients whose GVHD onset and IL-6 peak were within three days of each other (P = 0.02). These results, confirmed by both specific bioassay and by IL-6 ELISA, support the idea that acute GVHD in humans involves a cytokine cascade that includes production of IL-6 in addition to the previously reported involvement of tumor necrosis factor alpha and interferon-gamma.     

Karapandzic flap for reconstruction of lip defects.

PURPOSE: Systematic evaluation of the Karapandzic flap in the reconstruction of lip defects after ablative surgery. PATIENTS AND METHODS: Patients who had a Karapandzic flap to reconstruct lip defects were analyzed with reference to demographic details, histology and location of the tumor, and dimensions of resection. The functional aspects of the reconstruction were assessed in terms of the size of the oral stoma, preservation of oral competence, and facial expression, in addition to speech, diet and ease of cutlery, and denture usage. The esthetic outcome was assessed with a 4-point scale and in addition the symmetry of the commissure at rest and function, preservation of the philtrum, and lip projection also were assessed. The complications were noted. RESULTS: Seven patients underwent Karapandzic flap reconstruction (4 males, 3 females) with an age range of 43 to 98 years. Three tumors were located in the upper lip, 4 in the lower lip, and there were 5 squamous and 2 basal cell carcinomas. The lip defects ranged from 40% to 75% of the lip circumference. The oral stoma was of a reduced circumference in all cases but did not lead to any functional compromise in terms of oral competence, facial expression, speech, diet, denture and cutlery usage, and sensation. There were no wound complications in our series. The esthetic outcome was considered excellent/good in 85% of cases. The commissure was symmetrical in all except 1 patient, the philtrum was preserved in all cases of lower lip reconstruction, and the projection of the lip was reduced in edentulous patients. CONCLUSIONS: The Karapandzic flap is a reliable technique that offers consistently good functional and esthetic outcomes after reconstruction of lip defects.