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Biomedical subjects

L G Koss

Publications and source records attributed to L G Koss.

At least 127 records · Page 7Linked to original sources

Comparison of needle aspiration and solid biopsy technics in the flow cytometric study of DNA distributions of surgically resected tumors.

Flow cytometric analysis (FCM) of DNA content of nuclei was performed on simultaneously obtained tissue samples and needle aspirates from 37 primary colorectal cancers and from 21 other tumors. There was a marked increase in the proportion of the nondiploid cell population in 18 of 58 aspirates when compared with the corresponding tissue samples, presumably because of selective aspiration of tumor cells. The difference was significant at level alpha much less than 0.01 by a paired t-test and was most pronounced in tumors wherein a nondiploid population constituted more than 20% of the sample. The difference did not correlate with the grade or stage of the tumor. These observations suggest that the sampling of surgically resected tissue specimens for DNA analysis by FCM is performed best by needle aspiration, which may increase the yield of nondiploid cells, does not interfere with histologic diagnosis, and may prove especially useful in the analysis of small surgical specimens.

Biopsy↗

Thin-needle aspiration biopsy of the prostate.

The authors summarize the current status of thin-needle aspiration biopsy of the prostate and evaluate the accomplishments and limitations of this method of diagnosis. Historical developments, indications, technique, contraindications, complications, cytology of aspirates, diagnostic efficacy of aspirates, and grading of prostatic carcinomas are discussed.

Adenocarcinoma↗

Image analysis and DNA content of urothelial cells infected with human polyomavirus.

Human polyomavirus (HPV)-infected cells in the urinary sediment are characterized by large homogeneous basophilic nuclear inclusions, which may mimic the nuclear changes in urothelial cancer. The virus is composed of double-stranded DNA and produces intense green fluorescence of nuclei stained with acridine orange. DNA measurements of Feulgen-stained smears of urinary sediment disclosed that HPV-infected cells have aneuploid DNA values and could not be differentiated from cancer cells on the basis of DNA content alone. On the other hand, computer discriminant analysis performed on high-resolution images of HPV-infected and malignant urothelial cells stained by both the Papanicolaou and Feulgen methods showed that excellent discrimination between the two groups of cells could be achieved with either stain. The misclassification rates ranged from 3% to 9%. This differentiation was almost entirely based upon computer features pertaining to the texture of the nuclear chromatin. This study documented still further the diagnostic value of high-resolution image analysis of cells in the human urinary sediment.

Animals↗

Expression of Ca antigen in relation to cell cycle in cultured human tumor cells.

In order to explain the heterogeneity of Ca antigen (Ca) expression observed previously on human malignant cells, a relationship of antigen content with events in the cell cycle was studied by multiparameter flow cytometry on four continuous human cell lines, HeLaS3, C4l, HT29, and T24, grown exponentially in culture. In the four cell lines studied, there was an increase in Ca expression during the G1 and G2 + M phases whereas, during the S phase, the Ca expression was relatively constant. Although the level of Ca varied among the four cell lines, the mean amount of Ca expressed during the G2 + M phase was from 58 to 94% higher than the mean for the G1 phase. The G1 and G2 + M cell populations also displayed considerably greater variability of Ca content when compared with cells in the S phase. The level of Ca among cell lines appeared to have an inverse relationship to DNA content expressed as DNA index. Ca expression appeared to be related to RNA content and hence, presumably, ribosomal content, across the cell cycle. This study suggests that some of the heterogeneity of Ca expression in human cancer cells may be related to cell cycle events.

Antigens, Neoplasm↗

Interobserver and intraobserver differences in the diagnosis of urothelial cells. Comparison with classification by computer.

The diagnostic performance of six human observers with various degrees of experience was tested against the diagnosis developed by consensus and by an automated, computer-generated cell-classification system. The study was based on randomly selected photographs of 200 urothelial cells, classified in groups of 50 as negative, atypical, suspicious and malignant, from smears of urine sediment. The performance of the human observers was tested in three separate sessions at suitable time intervals and evaluated by two analytical statistical techniques: the weighted kappa proposed by Cohen, to evaluate the degree of disagreement, and the log-linear analysis of association. The results indicated considerable interobserver and intraobserver differences, which appeared to be more closely related to the individual's perception of the visual targets than to the degree of experience or the target itself. The performance of the programmed computer was well within the midrange of the human diagnostic performance. This study indicated that under the experimental circumstances described in this paper, the diagnostic perception of cell images is highly subjective. The study implies that similar differences may exist elsewhere in diagnostic microscopy and suggests that the development of objective approaches to the morphologic classification of human disease may prove to be of clinical value.

Computers↗

Detection of endometrial carcinoma and hyperplasia in asymptomatic women.

Occult endometrial carcinoma is a detectable disease using commercially available sampling devices and cytohistologic techniques. A cohort of 2586 asymptomatic women (98% past the age of 45, 78% caucasian) was screened. Of these women, 1567 were screened twice, and 187 were screened three times. The prevalence and incidence rates of endometrial carcinoma, as defined in the present study, including four missed cases, were 6.96 per 1000 and 1.71 per 1000 women years, respectively. The prevalence rate was 7.38 per 1000 for caucasian women and 5.40 per 1000 for women of other races. An epidemiologic evaluation suggested that the onset of menopause past the age of 49 was the only statistically significant risk factor, whereas race, parity, estrogen intake, and obesity, as calculated by the Quetelet index, were not statistically significant. The present study strongly suggests that in asymptomatic women past the age of 50, endometrial hyperplasia does not necessarily precede or accompany the development of endometrial carcinoma. Two distinct mechanisms may be responsible for the onset of endometrial cancer: endometrial hyperplasia occurring in the symptomatic and younger woman; and endometrial adenocarcinoma occurring ab initio in the older patient.

Adenocarcinoma↗

Nuclear pores and DNA ploidy in human bladder carcinomas.

The number of nuclear pores per sq micron was determined on the freeze-fractured nuclei of 20 human bladder tumors and five control samples of normal bladder epithelium. Measurements of the nuclear surface and volume were also performed, and the mean number of pores per nucleus and the ratio of pore to volume were calculated. The DNA distribution pattern on the same samples was determined by flow cytometry. All control samples and 12 tumors were diploid, and eight tumors were aneuploid. The mean number of pores per sq micron and mean total number of pores per nucleus in the control samples and in diploid tumors were similar. In the aneuploid tumors, both values were significantly higher. However, the ratio of pore to volume was shown to be constant regardless of the DNA content. It was further observed that, in aneuploid tumors, there are two populations of nuclei, one with density of pores similar to the diploid tumor and one with a higher pore density. Because aneuploid bladder tumors have been shown to have more aggressive behavior than diploid tumors, increased density of nuclear pores or their total number per nucleus may be related to tumor behavior. This view is supported by the observation that five of eight tumors with increased density and total pore number were invasive, while all tumors with low pore number were noninvasive.

DNA, Neoplasm↗

Primary choriocarcinoma of the urinary bladder. Report of a case with probable epithelial origin.

The seventh case of primary choriocarcinoma of the urinary bladder is presented. The results of initial bladder biopsies on this 82-year-old male patient revealed a poorly differentiated urothelial carcinoma and carcinoma in situ. The diagnosis of choriocarcinoma was established at autopsy, and confirmed by the demonstration of chorionic gonadotropin by immunoperoxidase technique. The literature is reviewed and a possible epithelial origin of this rare tumor is discussed.

Aged↗

Mapping of urothelium in carcinomas of the renal pelvis and ureter. A report of nine cases.

Complete histologic mapping of the urothelium was performed in nine surgical nephroureterectomy specimens. In seven patients, the primary lesion was carcinoma of the renal pelvis; in two, carcinoma of the ureter. In all cases, in areas peripheral to obvious carcinomas, there were extensive epithelial abnormalities akin to those previously described in mapping studies of the urinary bladder. The epithelial changes ranged from hyperplasia to flat carcinoma in situ. The latter was observed in four patients and appears to be an unfavorable prognostic sign: one of the four patients died of disease three months after surgery, and two patients developed metachronous carcinomas of the urinary bladder. Only one of these four patients has been free of disease for 21 months. One additional patient with atypical urothelium in the renal pelvis also developed a metachronous bladder cancer. Significant neoplastic abnormalities of the epithelium of the collecting ducts were observed in six of the seven cases of carcinoma of the renal pelvis. The study emphasizes the essential unity of the urothelium as a target organ for neoplastic events.

Aged↗

Histological grading and surface configuration of breast cancer cells. A comparative light microscopic, transmission and scanning electron microscopic study.

Scanning electron microscopic configuration of cells aspirated from breast cancer have been compared with histologic gradings according to the system proposed by Bloom and Richardson. The presence of pleomorphic microvilli correlated well with tumors grade I. The absence of pleomorphic microvilli correlated well with tumors grade III. Tumors graded as II showed a wide spectrum of surface configuration of cancer cells. It is possible that these observations may prove to be of prognostic value in breast cancer.

Biopsy, Needle↗

Scanning electron microscopy in cytodiagnosis.

This paper is an account of the application of scanning electron microscopy (SEM) to cytodiagnosis. We have investigated the diagnostic significance of SEM studies of cells derived from the uterine cervix, esophagus, stomach, bronchus, urinary bladder, pleural and peritoneal effusions and fine needle aspiration biopsy material. The occurrence of irregular, pleomorphic microvilli (MV) was found to be the most constant feature of cancer cells. Although SEM supplies additional morphologic data which, when used in conjunction with light microscopy, can assist in reaching the correct diagnosis in preselected cases, may contribute to the assessment of degree of tumor differentiation and may perhaps prove to be of value in screening patients at a higher risk for certain tumors, SEM is unlikely to be of value as a primary tool for cytologic diagnosis of cancer.

Adenocarcinoma↗

The use of hierarchic classification in the image analysis of a complex cell population. Experience with the sediment of voided urine.

Microscopic analysis of cells in the sediment of voided urine is the principal noninvasive method of diagnosing and detecting cancer of the lower urinary tract, mainly the bladder. The sediments contain several populations of cells of unequal diagnostic value. By applying a system of hierarchic classification to the computer analysis of digitized cell images, we were able to eliminate from diagnostic consideration cells that are difficult to classify, such as degenerated cells, multinucleated cells, cell clusters, renal tubular cells and cells infected by the human polyomavirus. When this method of triage was applied to the images of sequentially encountered epithelial cells and clusters, the cell images accepted for final analysis by the computer were sufficient in number and quality to automatically construct cytologic profiles of documented diagnostic value in 15 patients with bladder cancer. The method proved to be applicable to smears and quantitative cytocentrifuge preparations processed by methods developed in our laboratory. This work clearly documents the feasibility of automated analysis of cells in voided urine for the purpose of diagnosing bladder cancer. It also confirms prior observations suggesting that a relatively small sample of sequential images of epithelial cells (200 to 300) is sufficient to establish a diagnostic profile of clinical value on patients with high-grade cancer of the urinary bladder.

Computers↗