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Biomedical subjects

L G Koss

Publications and source records attributed to L G Koss.

At least 37 records · Page 2Linked to original sources

Significant reduction in the rate of false-negative cervical smears with neural network-based technology (PAPNET Testing System).

False-negative cervical Pap smears may lead to disability or death from carcinoma of the uterine cervix. New computer technology has led to the development of an interactive, neural network-based vision instrument to increase the accuracy of cervical smear screening. The instrument belongs to a new class of medical devices designed to provide computer-aided diagnosis (CADx). To test the instrument's performance, 487 archival negative smears (index smears) from 228 women with biopsy-documented high-grade precancerous lesions or invasive cervical carcinoma (index women) were retrieved from the files of 10 participating laboratories that were using federally mandated quality assurance procedures. Samples of sequential negative smears (total 9,666) were retrieved as controls. The instrument was used to identify evidence of missed cytological abnormalities, including atypical squamous or glandular cells of undetermined significance (ASCUS, AGUS), low-grade or high-grade squamous intraepithelial lesions (LSIL, HSIL) and carcinoma. Using the instrument, 98 false-negative index smears were identified in 72 of the 228 index women (31.6%, 95% confidence interval [CI]: 25% to 38%). Disregarding the debatable categories of ASCUS or AGUS, there were 44 women whose false-negative smears disclosed squamous intraepithelial lesions (SIL) or carcinoma (19.3%; 95% CI: 14.2% to 24.4%). Unexpectedly, SILs were also identified in 127 of 9,666 control negative smears (1.3%; 95% CI: 1.1% to 1.5%). Compared with historical performance data from several participating laboratories, the instrument increased the detection rate of SILs in control smears by 25% and increased the yield of quality control rescreening 5.1 times (P < 0.0001). These data provide evidence that conventional screening and quality control rescreening of cervical smears fail to identify a substantial number of abnormalities. A significant improvement in performance of screening of cervical smears could be achieved with the use of the instrument described in this report.

Carcinoma in Situ↗

Automated sputum screening with PAPNET system: a study of 122 cases.

The use of interactive, computerized PAPNET system (Neuromedical Systems, Inc, Suffern, NY) for screening of cervicovaginal smears has been favorably evaluated in several studies. In this article, the authors report on the performance of this apparatus on smears of sputum. One hundred twenty-two randomly selected, single slides of sputum specimens from an equal number of patients were subjected to PAPNET scanning. These Papanicolaou-stained slides were previously classified as inadequate, six; negative, 81; atypical, three; suspicious, one; and positive for malignant cells, 31. Images selected by PAPNET were reviewed by two observers, who were blinded to earlier interpretation and triaged into two categories: negative and review. Of the 31 smears with cancer cells, 30 were appropriately identified by PAPNET (sensitivity: 97.1%). The only case missed by PAPNET was that of small cell carcinoma that contained a single cluster of neoplastic cells. PAPNET also triggered the review of 20 of the "negative" cases, which on re-evaluation were identified as bronchial cells with squamous metaplasia and altered benign squamous cells of inflammatory type. A prospective study of PAPNET for screening of sputum samples is needed to establish the clinical value of this methodology.

Cytodiagnosis↗

Detection of occult endometrial carcinoma.

Endometrial carcinoma is commonly diagnosed as a consequence of abnormal uterine bleeding. In a study published in 1962, it was documented that endometrial cancer may be detected by vaginal pool smears in asymptomatic postmenopausal women. As a consequence of these observation, a systematic search for occult endometrial carcinoma was initiated in 1979, supported by a contract from the National Cancer Institute. The techniques used in this study and the problems encountered in the diagnosis of occult endometrial carcinoma will be discussed. Within 3-1/2 years of this study encompassing 2,586 peri- or postmenopausal women 16 occult endometrial carcinomas were discovered by direct endometrial sampling. Two carcinomas, missed on initial screening, were subsequently documented in this cohort, for a prevalence rate of 6.96 per 1,000. The incidence data based on follow-up examination of 1,754 women was 1.71 per 1,000 woman-years. An elaborate epidemiologic questionnaire was evaluated. Contrary to some prevailing views, obesity, hypertension, and diabetes failed to reach statistical significance as risk factors. The only risk factor of statistical value was delay in the onset of menopause past age 49, observed in about 50% of the cohort. It was noted that the administration of estrogens to women in Quetelet Index groups below means was more likely to be associated with carcinoma than in women in higher Quetelet groups but, again, the difference was not statistically significant. It was noted that in spite of an active search for endometrial hyperplasias, the rate of these lesions was nearly identical to the prevalence and incidence rates for carcinoma. It was postulated that some or perhaps most, endometrial carcinomas in postmenopausal women are not preceded by hyperplasia but originate ab initio in the endometrium.

Adult↗

Evaluation of the PAPNET cytologic screening system for quality control of cervical smears.

The PAPNET system is an automated interactive instrument for analysis of conventional (Papanicolaou) cervical smears. The instrument, described in this paper, introduces several important innovations to cytology automation. The cell selection system is composed of two stages: an algorithmic classifier, followed by a trained neural network allowing for great flexibility and precision in recognition of abnormal cell images. Contrary to other attempts at cytology automation, this machine does not attempt to diagnose cell abnormalities. Instead, it is interactive, leaving the assessment of the cells displayed on a high-resolution video screen to trained human observers. The slides judged to contain abnormal cells or to be inadequate are referred for a second microscopic review. Two versions of the instrument (Alpha and Beta) were evaluated in several modes. Initial testing was performed on archival smears with known, histologically confirmed neoplastic lesions of the uterine cervix. These lesions comprised the entire spectrum of abnormalities, from low-grade lesions to invasive cancers of several types. The Alpha machine displayed recognizable abnormal cells in 97% of the 201 cases, and the Beta machine displayed such cells in 97.2% of 176 cases. The Beta instrument was subsequently tested on 500 sequential archival cervical smears that had been previously subjected to a rigorous quality control. One hundred forty smears (28%), which either displayed atypical cells or were considered "inadequate," were referred for further rescreening. Fifteen of 16 previously diagnosed neoplastic smears were appropriately identified with the help of the machine. The one missed case contained a single cluster of vacuolated cancer cells from an endometrial carcinoma. As a result of PAPNET-triggered review, three new cases of low-grade squamous intraepithelial lesions view, three new cases of low-grade squamous intraepithelial lesions (SIL) came to light in previously negative smears; three additional cases, previously classified as atypical, were also reclassified as SIL, for a net gain of six neoplastic abnormalities. In two additional atypical cases, colposcopic follow-up was recommended, even though the diagnosis was not modified. Two cases of cervical intraepithelial neoplasia, represented by tiny single clusters of abnormal cells missed on original screening, quality control, and on machine rescreening, came to light on second review of the residual 360 cases. The initial experience with the PAPNET system suggests that the instrument may be valuable in quality control and may assist in significantly reducing false-negative cervical smears in an efficient and timely manner. Further testing of the instrument on a much larger number of cervical smears is in progress.

Algorithms↗

Reducing the error rate in Papanicolaou smears. One laboratory's experience with the PAPNET system.

False-negative Papanicolaou smears not only endanger the patient's life, but may also lead to legal problems for the clinician. The PAPNET interactive computerized system has been shown to reduce the false-negative rate in the author's laboratory, and disclosed the presence of atypical or cancerous cells in prior false-negative smears in a number of patients with invasive carcinoma.

Adult↗

Quantitative and analytical cytology in historical perspective.

A brief review of the historical events leading to developments of image analysis and flow cytometry is presented. The principles, accomplishments, and pitfalls of both techniques of quantitation of cell components and specific applications to markers potentially useful in cancer chemoprevention are discussed.

Cells↗

Cervical (Pap) smear. New directions.

This article reports the historic background leading to the introduction of cervical smears as a tool in the detection of precancerous changes in the uterine cervix. The false-negative error rate in the primary screening process is discussed and illustrated by data recently compiled from this laboratory. Rescreening of approximately 25% of cervical smears yielded an error screening rate of approximately 5% of precancerous lesions and cancer of the uterine cervix. The total false-negative screening error rate was much higher but was unknown and should be determined by additional studies. The reasons for the false-negative screening errors are discussed. Some of the proposed remedies, particularly screening of the entire population for human papillomavirus infection, are judged to be unacceptable because of the high prevalence of this virus in well women and because the biologic events linking the presence of viral DNA with the development of precancerous lesions are unknown. Screening assistance with the help of a newly developed interactive machine, combining image analysis with a neural net was promising as a tool in quality control.

Adolescent↗

Cytologic diagnosis of oral, esophageal, and peripheral lung cancer.

Oral cavity. Most carcinomas in situ of the oral cavity present as red or pink lesions that do not have a keratinized surface. Scrapings of such lesions readily disclose abnormal squamous cells diagnostic of cancer. Scrapings of the keratinized white lesions (so-called leukoplakia) are of no diagnostic value. Dentists, who are most likely to uncover precancerous lesions, are apparently not aware of the diagnostic options based on simple scrape smears. The method is also applicable to follow-up of patients with treated cancer of the oral cavity. Esophagus. Cytologic evaluation of esophageal cancer, initially by washings and subsequently by brushings under endoscopic control, is an established method of diagnosis. The diagnostic results are very good in symptomatic cancer patients and have an accuracy reaching 85-90%. Unfortunately the results of treatment of advanced lesions are very poor, with 5-year survival of only about 5%. Serious efforts at detection of early esophageal cancer started in China in the 1960s, using an abrasive balloon technique which was applied to asymptomatic populations in high risk areas such as Linxian in the Henan province of Central China. The Chinese investigators reported the finding of numerous precancerous lesions of the esophagus classified as carcinoma in situ and as dysplasia. Surgical resection of some of the precursor lesions apparently resulted in a significant drop in the rate of invasive carcinoma, although the statistical results were not convincingly presented. The balloon technique has been tested by us and by others in South Africa and in Transkei, confirming its efficacy in the diagnosis of early esophageal cancer. Peripheral lung. Sputum and bronchial brush cytology may uncover bronchogenic carcinoma in situ and early invasive cancers located in the primary or secondary bronchi. Small, peripheral lung lesions usually do not shed cells in sputum or brushings, and their discovery is usually based on roentgenologic finding. The identity of such lesions can be confirmed in most cases by a transcutaneous aspiration. Most of the peripheral malignant lesions are small adenocarcinomas or epidermoid carcinomas, both resectable by routine surgical procedures. Less commonly, oat cell carcinomas may be observed and these lesions should not be treated by surgery. Benign lesions such as granulomatous inflammation and fungal infections may also be identified by aspiration techniques. The prognosis of the resectable carcinomas varies with their size and the presence or absence of regional lymph node metastases.(ABSTRACT TRUNCATED AT 400 WORDS)

Cytodiagnosis↗

Diagnostic cytology of small mammary carcinomas.

This brief article summarizes the historical background of the thin needle aspiration technique as it applies to diseases of the breast. The technique and the achievements of this method in the diagnosis of small breast cancers are reported. A brief note on the value of nipple secretions in the diagnosis of carcinoma of the mammary ducts is appended.

Biopsy, Needle↗