John K. Frost

Sister chromatid exchanges in the peripheral blood of cigarette smokers and in lung cancer patients; and the effect of chemotherapy

SummaryPeripheral blood sister chromatid exchange (SCE) rates in chronic cigarette smokers and in subjects with cancer do not differ from those in healthy nonsmokers. SCE patterns were normal in 69 chronic cigarette smokers, including 62 patients with untreated lung cancer. In three chronic smokers with lung cancer, high SCE levels were related to recent intravenous chemotherapy.

Sputum cytopathology: use and potential in monitoring the workplace environment by screening for biological effects of exposure

Sputum cytopathologic monitoring detects squamous cell lung cancers at an extremely early stage (x-ray negative). It holds further potential for preventing disease by detecting epithelial alterations which reflect environmental hazards. The addition of sputum cytology screening to screening by chest x-ray film does not significantly reduce mortality from all types of lung cancer, but preliminary analysis of Johns Hopkins Lung Project data suggests that mortality from squamous cell carcinoma is reduced. Quantitative automated cytopathology systems and biochemical/immunological cell markers enhance understanding of these precursors and offer great promise for increasing capacity, accuracy, and usefulness in cytopathology screening of workers. Cytological specimens collected over years of screening workers considered at risk may be important to eventually understanding development and prevention of major occupational diseases.

Cytologic detection and clinical significance of Actinomyces israelii in women using intrauterine contraceptive devices

Pancervicovaginal (Papanicolaou) smears exhibiting pseudomycilial-like clumps of organisms obtained from 35 women employing IUDs were studied by direct immunofluorescent technique for identification of A. israelii and A. naeslundi. In every case the specific fluorescence was achieved with species-specific antiserum against A. israelii. The clinical profile of these 35 women was retrospectively analyzed.

Flexible fiberoptic bronchoscopy. Its place in the search for lung cancer

The use of sputum cytology has demonstrated that conventional bronchoscopic equipment often fails to permit localization of earlier, more peripheral tumors. The flexible fiberbronchoscope now opens up new bronchial horizons but does not replace rigid instruments. Our experience in 300 fiberoptic studies has suggested certain guidelines for determining in which patients the flexible equipment should be used and in which conventional instruments are preferred. By means of a comprehensive endoscopic study, we successfully localized eight “sputum positive,” radiologically occult bronchogenic carcinomas. The fiberbronchoscope is essential in searching the segments for subtle changes of early cancer. These findings are documented by a color television system. A detailed pathological study demonstrates the importance of preoperative marginal biopsies in excluding carcinoma in situ which may extend some distance from even small tumors. In 94 patients with cancer we located 85 (90%) by direct visualization and/or bronchoscopic specimens. Sixty-eight (72%) involved primarily the segmental or more peripheral areas while main bronchus tumors were large and suggested spread from a more distal site of origin. The fiberbronchoscope has greatly extended our capabilities, allowing a better understanding of early lung cancer and greatly improved localization.

Occult bronchogenic carcinoma. Endoscopic localization and television documentation.

Early bronchogenic carcinoma detected by sputum cytology frequently cannot be localized by conventional bronchoscopic techniques. Six occult tumors were localized in this study with new techniques in differential cytology and flexible fiberoptic equipment. A three‐phase study is carried out including: 1. Cytologic localization, 2. Fiberoptic survey, and 3. Histologic mapping of bronchial margins. Findings are recorded by means of a color television documentation system. A review of the surgical pathology in our four cases has revealed a relatively large area of in‐situ carcinoma in the region of very small invasive tumors.

Pulmonary cytologic alterations in toxic environmental inhalation

Abstract Toxic elements of the environment adversely affect tissues, structures, and functions of the respiratory system. Many of these changes are reflected in cells and other elements of pulmonary secretions. Natural defense mechanisms of the respiratory tract are impaired, rendered less effective, and eventually invalidated by toxic inhalants. Tissue changes in response to these toxic inhalants and irritants, especially of the, epithelium can be studied and evaluated cytologically with detection and identification of the various degrees of atypia. These cytologic alterations appear to be valid indications of the carcinogenic potentialities of environmental toxins. In three occupational groups increased frequency of these changes appear to parallel the presence of known or suspected carcinogenic environmental substances. Their cytologic identification may thus help to indicate those individuals or groups for whom preventive or other measures are most needed.

Relationships of morphology to clinical presentation in ten cases of early squamous cell carcinoma of the lung

The morphologic changes in 10 patients who were found to have squamous cell carcinoma of the lung before they became evident on chest x ray are discussed. It is suggested that these cases have a long preclinical course as invasive carcinomas that ranges from a microscopic focus of microinvasion (possibly originating from in situ carcinoma in submucosal gland epithelium) to a large concentric carcinoma which may have metastasized to regional lymph nodes. Although the duration of the in situ phase of squamous cell carcinoma of the bronchus is not known, it was evident that the expanse of in situ carcinoma frequently far exceeded that of the invasive carcinoma, and usually extended proximal to the invasive lesion. It is important that the extent of the in situ lesion is determined preoperatively. Finally, multifocal in situ (or invasive) carcinoma was found in at least two of the cases, either synchronously or metachronously.

The value of the assay of chromosomes in the diagnosis of cervical neoplasia.

Abstract Available studies indicate that if a direct squash technique is used, chromosomal aneuploidy is a very constant finding in invasive and in intraepithelial carcinoma of the cervix. The significance of aneuploidy in cervical epithelium in which the changes are insufficient to justify a diagnosis of cancer is therefore of theoretical and practical importance. To study this problem chromosomes of cervical epithelium were examined by the direct squash technique in 25 patients with normal or nearly normal histopathologic findings in the cervix. Very few spreads were seen in this group of cases but, when present, were diploid. Five of 6 patients with intraepithelial carcinoma had aneuploid chromosomes. Eight of 21 patients with cervical atypia also had aneuploid chromosomes. It is suggested that the present evidence favors the view that cells from a focus of cervical atypia which yield aneuploid chromosomes are malignant.

Automatic Cell Identification and Enrichment in Lung Cancer III. Light Scatter and Two Fluorescence Parameters

Two physical parameters were investigated to automatically recognize cells in sputum from human squamous cell carcinoma of the lung and to separate them for preparation by the Papanicolaou methods, for human interactive identification and for automated high resolution image analysis. The two parameters, 0.5-15.0 degrees forward argon-ion laser light scatter to estimate total cell size and 546 nm Acridine orange fluorescence to approximate total cell DNA content, were measured in a flow-through fluorescence activated cell sorting system. Enrichment for neoplastic cells in three cases of squamous cell carcinoma of the lung averaged 7.8-fold over the original sputum when only green fluorescence was used and 10.5-fold using green fluorescence and forward light scatter. The average enrichment for neoplastic cells was 65.6-fold relative to polymorphonuclear deenrichment.

Cytopathology and Histopathology of the Female Genital Tract in Trichomonas vaginalis Infection

Four species of trichomonads inhabit humans: Trichomonas vaginalis, described initially by Donne,1 Trichomonads tenax, first seen by O.F. Muller,2 Pentatrichomonas hominis, reported originally by Davaine,3 and Trichomitus fecalis, isolated by Cleveland.4