Randomized placebo-controlled trial of isotretinoin in chemoprevention of bronchial squamous metaplasia.

PURPOSE: Retinoids have proven chemopreventive efficacy in both preclinical and clinical studies. This trial was designed to confirm the finding of an earlier uncontrolled trial that the synthetic retinoid etretinate had major activity in reversing squamous metaplasia found in the bronchial epithelium of chronic smokers. PATIENTS AND METHODS: We prospectively evaluated 152 smokers with bronchoscopy and obtained biopsies from six sites. Subjects with dysplasia and/or a metaplasia index of greater than 15% were randomly assigned to receive either 1 mg/kg isotretinoin or placebo daily for 6 months. Of 86 subjects randomized (41 isotretinoin, 45 placebo), 69 were reevaluated at the completion of treatment. RESULTS: In the group as a whole, the metaplasia index decreased over time from a mean +/- SE of 35.8% +/- 2.7% at baseline to 28.1% +/- 3.3% at the completion of treatment (P = .01) by repeated measures analysis of variance [ANOVA]); a reduction in the metaplasia index (> 8%) was noted in both isotretinoin and placebo groups (19 of 35 [54.3%] and 20 of 34 [58.8%], respectively). Complete reversal of squamous metaplasia was noted in nine subjects from each group. However, the magnitudes of the mean metaplasia index changes did not differ significantly in the two treatment groups. In both groups, smoking cessation resulted in significant declines in the extent of squamous metaplasia, whereas no significant change in metaplasia index was found among those who continued to smoke. CONCLUSION: Squamous metaplasia was frequently observed in bronchial biopsy samples from chronic smokers. From this study, we conclude that isotretinoin has no effect on squamous metaplasia, a potential intermediate end point of bronchial carcinogenesis. Although determining the exact role of isotretinoin in lung cancer prevention requires further study, the finding that there was a significant decrease in squamous metaplasia in the placebo group emphasizes the critical importance of a placebo-controlled study design in chemoprevention trials using intermediate end points.

Radiation-induced malignant pleural mesothelioma.

Malignant pleural mesothelioma is a rare and usually fatal disease. Its association with asbestosis is well recognized. The authors report a case of malignant pleural mesothelioma that developed 30 years after the patient underwent radiotherapy for breast cancer. This appears to be the first such case reported in the radiology literature.

Lung cancer classification: the relationship of disease extent and cell type to survival in a clinical trials population.

The staging and histologic cell type of patients in the Lung Cancer Study Group (LCSG) clinical trials program are reviewed and confirmed or resolved at the reference center for anatomic and pathologic classification of lung cancer. A high level of consistency in classification has been achieved through the use of criteria that minimize intraobserver variability. The data obtained from the review project have been used to characterize the relationship of disease extent and cell type to survival in the clinical trials population. Survival characteristics were generated for 1,121 patients who underwent apparent complete resection of nonsmall cell lung cancer and were subsequently entered into various protocols to receive either adjuvant treatment or no further therapy. The end results study provides some insight regarding the biological behavior of squamous cell carcinoma and adenocarcinoma of the lung in terms of the anatomic extent of disease at the time of apparent complete resection. Patients with squamous cell carcinoma had an outcome superior to that of patients with adenocarcinoma in every TNM subset. The differences in survival according to these major cell types were significant overall and in the T1 N0, T1 N1, and T2 N1 subsets but not in the TNM subsets in stage III disease. Histologic cell type and extent of disease are important factors in survival expectations; thus the accuracy and reproducibility of these classifications plays a significant role in the evaluation of differing modalities of treatment.

Prognostic factors in patients with resected stage I non-small cell lung cancer. A report from the Lung Cancer Study Group.

The authors present prognostic information on recurrence and survival for resected Stage I lung cancer patients with squamous cell carcinoma, adenocarcinoma or large cell carcinoma. The data derive from 392 carefully staged patients and include results from the history and physical examination, preoperative laboratory tests, nature of the surgery, complications, initial pathologic findings following surgical resection, and final pathologic review. A simple multivariate model of recurrence, which is used to classify patients into low, intermediate, and high-risk groups, is based on tumor size and location (T1, T2), histologic type (squamous, nonsquamous/mixed) and nodal status (N0, N1). To model survival, the performance status and the presence of empyema, pneumonia, or wound infection were added to the previous factors. Not all factors associated with increased mortality are associated with increased risk of recurrence, and, in particular, postoperative empyema, pneumonia or wound infections carry an increased risk of death only. Serial measurements of performance status and leukocyte count have the potential for monitoring for increased risk of recurrence and death.

Endoscopic cytology and biopsy diagnosis of esophageal carcinoma.

We examined 107 cytology and biopsy specimens taken simultaneously from 103 patients to determine the efficacy of cytologic esophageal brushing in the diagnosis of esophageal carcinoma. After review of all material, cytology was positive in 84% of cases, biopsy in 86%, and combined specimens (cytology and biopsy) in 94%. However, agreement as to histologic type was reached in only 53 of the 63 specimens originally reported as positive by both cytology and biopsy.

Spontaneous regression of breast carcinoma: follow-up report and literature review.

A case of spontaneous complete regression of metastatic breast carcinoma (malignant pleural effusion and bone metastases) with previously reported from M. D. Anderson Hospital and Tumor Institute. The patient did not receive any form of hormonal manipulation or systemic chemotherapy. This patient has now relapsed after 72 months of spontaneous complete remission, and a follow-up of her clinical history is presented. A search of the literature for previously reported instances of spontaneous regression of breast carcinoma indicates that this event is exceedingly rare.

Fibrous histiocytoma of lung--a clinicopathological study of two cases.

Two cases of fibrohistiocytic tumours of the lung are presented and histogenesis of this group of this group of tumours is discussed. An essentially biphasic pattern of histiocytes and fibroblasts, and the presence of myofibroblasts and undifferentiated mesenchymal cells is similar to the fibro histiocytic neoplasms in other locations.

Diagnosis of eosinophilic granuloma of bone by cytology, histology, and electron microscopy of transcutaneous bone-aspiration biopsy.

The cytological, histological, and ultrastructural morphology of transcutaneous bone aspirates from five patients with eosinophilic granuloma of bone were studied. Use of this combined approach enabled us to make a definitive diagnosis of eosinophilic granuloma from a small quantity of tissue without having to resort to open biopsy. By light microscopy, eosinophilic granuloma is composed of a polymorphous infiltrate of characteristic lobulated histiocytes, eosinophils, polymorphonuclear leukocytes, and giant cells. Each specimen examined ultrastructurally demonstrated the characteristic Langerhans granule-containing histiocyte. Eosinophilic granuloma is a benign lesion which is readily diagnosed by this technique, and more aggressive diagnostic procedures usually are not warranted.

The comparative diagnostic accuracy of cancer-cell detection obtained with Ficoll-Hypaque gradient separation and standard centrifugation technics on body-cavity fluids.

Ninety-two consecutive samples of body-cavity fluids from patients with confirmed or suspected cancer were compared for accuracy of diagnosis using a Ficoll gradient test and a standard centrifugation test. The percentage of positive test results was 76% (70/92) with the Ficoll test and 64% (59/92) with the routine test. The Ficoll and routine tests also gave a significant difference in the classification of malignancy, with the latter test giving a significantly higher proportion of negative or inconclusive test results. Besides the improved test results, the Ficoll gradient test has the further advantages of being less expensive and requiring only standard laboratory equipment. Elimination of blood and cellular debris by the procedure results in quick and easy cytologic screening. The Ficoll test is strongly recommended for those clinical fluids suspected to be positive for malignancy, especially where the routine test is negative or inconclusive.

Oncocytic carcinoid tumor of the lung.

A case of bronchial carcinoid tumor is reported in which a marked degree of transformation to mitochondrion-rich cells (oncocytes) was present. Ultrastructural observations demonstrated a transition between the two cell types, and revealed an alteration in mitochondria suggestive of a degenerative change in these organelles.

Spontaneous regression of breast carcinoma.

Spontaneous regression of breast carcinoma occurred in a patient with a malignant pleural effusion and bone metastases. The patient did not receive any form of hormonal manipulation or systemic chemotherapy. It is postulated that the spontaneous regression of the carcinoma may have been caused by immunological factors.

Percutaneous needle biopsy of bone in the cancer patient.

Needle biopsy of skeletal lesions is easily accomplished by the percutaneous technique. Although this approach has been utilized for many years, the frequency has definitely increased of the 91 cases performed at M. D. Anderson Hospital and Tumor Institute from September 1976 to September 1977, adequate material was obtained in 92.3% of the patients, and the diagnosis was established accurately in 83.5% of the cases. No complications were encountered. The technique, indications, and contraindications are discussed and illustrated with representative cases. The contribution of this technique to the management of patients with malignant disease is significant. The benefits include rapid and accurate establishment of a tissue diagnosis, avoidance of a surgical procedure with its associated risks and cost, and simplicity and safety of the procedure facilitating its repetition if needed.

Fine needle aspiration biopsy of retroperitoneal lymph nodes and abdominal masses: an updated report.

Percutaneous fine needle aspiration biopsy of retroperitoneal lymph nodes and abdominal masses was performed in 109 patients. Eighty-five per cent of the aspiration biopsies yielded sufficient cytologic material for a correct diagnosis. Indications include confirmation of lymphangiographic findings and the establishment of a histologic diagnosis in lieu of surgery. No significant complications were encountered.

Aspiration biopsy of discrete pulmonary lesions using a new thin needle. Results in the first 100 cases.

The authors describe their initial experience with a new thin spinal-type needle for aspiration biopsy of the lung. One hundred patients with discrete pulmonary lesions were studied. Diagnosis was possible in 87% of cases, and no significant complications were encountered.