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Biomedical subjects

D M Lowell

Publications and source records attributed to D M Lowell.

At least 19 recordsLinked to original sources

Risk factors for rapid-onset cervical cancer.

OBJECTIVES: The current study was designed to elucidate risk factors associated with the development of cervical cancer during the course of routine Papanicolaou smear screening (rapid-onset cervical cancer). STUDY DESIGN: Four hundred eighty-three women diagnosed with invasive cervical cancer, representing 73% of all such tumors diagnosed in Connecticut between 1985 and 1990, were studied. Papanicolaou smear screening and risk factor information was obtained by questionnaire and physician record review. Results from human papillomavirus deoxyribonucleic acid testing by polymerase chain reaction of tumor samples were available for 278 study participants. Prediagnostic Papanicolaou smear slides were reviewed for 67% of cases with a screening history. Screening history information, slide review, and questionnaire data were used to classify women as having rapid-onset cervical cancer (n = 43), possible rapid-onset cervical cancer (n = 111), or normal-onset cervical cancer (n = 329). RESULTS: Compared with normal-onset cases, rapid-onset cases tended to be younger (P =.001) and were more likely to be white (P =.002), diagnosed with adenocarcinomas or adenosquamous carcinomas (P =.001), and diagnosed with early-stage disease (P =.001). Cases diagnosed as possible rapid-onset disease tended to have a profile that was intermediate to that observed for rapid-onset and normal-onset cases. Human papillomavirus deoxyribonucleic acid was detected in 75.2% of cases tested. Compared with women who tested positive for human papillomavirus type 16 or other, those positive for human papillomavirus type 18 had a relative risk for rapid-onset disease of 1.6 (95% confidence interval 0.52-4.9). No significant association was observed between type 18 and possible rapid-onset disease when possible rapid-onset cases were compared with women diagnosed with normal-onset cervical cancer (relative risk 0.67, 95% confidence interval 0.29-1.6). Oral contraceptive use, cigarette smoking, number of pregnancies, and a maternal history of cervical cancer were not significantly associated with rapid-onset disease. CONCLUSIONS: Results from this study suggest that the risk factors associated with the development of rapid-onset cervical cancer are similar to those for normal-onset disease.

Adenocarcinoma↗

Rapidly progressive cervical cancer: the Connecticut experience.

A review is presented of 15 years of clinical experience working with women who developed cervical cancer within a short interval after the last reported negative Papanicolaou smear. Our initial report concerned isolated cases in which women were diagnosed with invasive cervical cancer within 1 year of a reported normal Papanicolaou smear. Our second report focused on a 10-year review of the Yale-New Haven Hospital experience, during which 40 of 555 women had rapidly progressive invasive disease; 35 cases (87.5%) occurred in women younger than 40 years old and almost all of the 40 diagnosed because of persistent symptoms despite a recent normal Papanicolaou smear. Our final experience is a population-based study of all women in Connecticut who developed cervical cancer between 1985 and 1990. A total of 118 of 481 (24.5%) participants were diagnosed with cervical cancer within 3 years of their last true-negative Papanicolaou smear. Adenocarcinomas occurred in 38 cases (32.2%). These data suggest that rapidly occurring cervical cancer may be a manifestation of endocervical carcinomas that have been inadequately screened.

Adenocarcinoma↗

The screening histories of women with invasive cervical cancer, Connecticut.

OBJECTIVES: Each case of a continuous series of invasive cervical cancer cases was studied with a structured review procedure conducted by an expert panel to assess the reason that it was not detected before it became invasive. METHODS: All cases of invasive cervical cancer diagnosed in a 5-year period among Connecticut residents were identified; a screening history and screening outcome were obtained for 72% (481 of 664). RESULTS: Two hundred fifty women (51.9%) had suboptimal screening. One hundred thirty-seven women (28.5%) had never had a screening test, and their mean age was greater than that of the rest of the study population (64.5 years vs 46.5 years). Of the 344 women who had ever had a Pap test, 113 (32.8%) had their last Pap test 5 or more years before their diagnosis of invasive cancer; 52 (15.1%) were not followed up properly; 33 (9.6%) had their last smear misread as normal; and 118 (34.3%) developed cervical cancer within 3 years of their last Pap test. CONCLUSIONS: Physicians, nurses, and other care providers need to ensure that woman have timely and accurate screening with proper follow-up, make increased efforts to reach older women, and improve quality control of Pap smear readings.

Adenocarcinoma↗

Improving accuracy in gynecologic cytology. Results of the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology.

The College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology (PAP) is a quarterly mailed glass-slide quality improvement program. This growing program started as a pilot in 1989 with 207 laboratories. In 1991, 605 laboratories participated. The diagnostic menu is modified from the Bethesda System and divides referenced slides into a negative series (normal, infectious, and reactive) and a positive series of epithelial lesions. A facsimile option facilitates immediate educational feedback. The 1989 through 1991 major discrepancy rate averaged 5%. The consensus laboratory response had higher concordance than either pathologist or cytotechnologist responses. Low-grade squamous intraepithelial lesion was the leading cause of false-negative participant response, while reactive/reparative change was the leading cause of false-positive response. Pathologist false-negative and false-positive responses from group or large case-volume practices were significantly lower than those from solo or small case-volume practices. Cytotechnologists in multiple-technologist or large-volume laboratories had significantly lower false-negative responses than solo technologists or those in low case-volume laboratories, but false-positive rates did not differ. Experienced participants had fewer major discrepancies. The Interlaboratory Comparison Program in Cervicovaginal Cytology illustrates the feasibility of a large, mailed glass-slide program, and offers laboratories a continuous method for monitoring and improving performance in gynecologic cytology.

Cytodiagnosis↗

Cervical intraepithelial neoplasia among women with papillomavirus infection compared to women with Trichomonas infection.

This study was undertaken to determine if women with papillomavirus infection were more likely to develop cervical intraepithelial neoplasia (CIN) than women with other sexually transmitted infections. Women with cytologic evidence of papillomavirus infection and a comparison group of women with cytologic evidence of Trichomonas infection were identified from a reexamination of cervicovaginal smears initially evaluated between 1973 and 1981 in a private pathology laboratory. To identify subsequent CIN among these women the authors reviewed records of private obstetric and gynecology practices and public clinics through 1983. After accounting for possible confounding variables, including age, marital status, frequency of cervical cytologic examination, and selected characteristics of pregnancy history, a 2.7-fold increase in the rate of CIN was found among the 613 women with prior papillomavirus infection compared to the 410 women with previous Trichomomas infection. The rate ratio was higher among women with more severe cervical neoplasia than for those with less severe neoplasia and for those followed for greater than 12 months than for those followed 7 to 12 months. The results of this study provide further evidence of the role of papillomavirus in the etiology of cervical cancer.

Adult↗

Flow cytometric analysis of DNA content in Hürthle cell adenomas and carcinomas of the thyroid.

Paraffin-embedded surgical biopsy material from 17 Hürthle cell tumors of the thyroid was examined for DNA content by flow cytometry to assess the diagnostic and prognostic utility of ploidy determinations in these rare tumors. Both adenomas (11 cases) and carcinomas (6 cases) were studied. As a control for methods, ten randomly selected normal autopsy thyroids were analyzed, all of which demonstrated normal diploid DNA content. Among the Hürthle cell tumors, however, aneuploid peaks were present in six adenomas (55%) and in four carcinomas (67%). Similarly, polyploid DNA peaks in the absence of other aneuploid peaks were present in two adenomas and two carcinomas (18% and 33%, respectively). These findings demonstrate the limited value of aneuploidy or polyploidy as diagnostic features for malignancy in Hürthle cell tumors of the thyroid. As for prognosis, there does not appear to be any unfavorable prognostic significance for abnormal DNA content in histologically benign Hürthle cell tumors treated by surgical excision because no metastases or recurrences occurred in this group at a mean disease-free follow-up of 50 +/- 19 months for six aneuploid lesions and 19 +/- 7 months for two polyploid adenomas. Preliminary data suggest that aneuploidy may, however, have an important prognostic value for histologically defined Hürthle cell carcinomas, because the only patient to die from the tumor in this series had an aneuploid Hürthle carcinoma. Thus, the authors' data indicate that the diagnostic utility of DNA content in Hürthle cell tumors is extremely limited and that there does not appear to be any negative prognostic significance for aneuploidy in histologically defined Hürthle cell adenomas.

Adenoma↗

Koilocytosis preceding squamous cell carcinoma in situ of uterine cervix.

Association of koilocytic changes with cervical squamous cell carcinoma is well documented. The studies of such concurrent association may miss those cases of papillomavirus infection where cytomorphologic expression of virus has disappeared by the time carcinoma appears. The authors studied cytologic material before the diagnosis was made of cervical squamous cell carcinoma in situ in 25 patients. Twenty-two (88%) of the 25 patients showed koilocytosis compared with only 6 out of 57 (10.5%) in the control group. The findings of this study support a possible predisposing role of papillomavirus in squamous cell carcinoma of the cervix.

Antigens, Viral↗

Aspiration of the breast and nipple discharge cytology.

Between 1 January 1974 and 30 June 1984, 1,003 specimens obtained from the breast were submitted for cytologic evaluation to the Department of Pathology at the Waterbury Hospital Health Center. Eighty-eight per cent were obtained by fine needle aspiration of a palpable mass; the remainder were smears of nipple discharges. Precytologic and postcytologic clinical data were available for 80 per cent of the specimens. In the fine needle aspiration group, there were 219 instances of proved carcinomas; 79 per cent of these had either positive or suspicious cytologic findings. Seventy-five per cent of the patients with positive cytologic results underwent mastectomy without prior histologic confirmation of the needle aspiration and all were confirmed as malignant growths. There were 41 false-negative aspirates which were reviewed in detail. The cytologic slides of 24 of the 41 false-negative aspirates were available for re-evaluation by a second, independent cytopathologist. Only one was thought to have been misread initially; the remainder appeared to have been falsely negative for technical reasons related to aspiration or fixation technique or tumor size less than 1 centimeter. There was one false-positive finding in a patient who was found to have fat necrosis at biopsy. Results of nipple discharge cytology were less accurate. Positive or suspicious cytology was found in only five of 11 proved instances of carcinomas. There was one false-positive and five false-negative results in this group. We conclude that needle aspiration of palpable masses of the breast is an accurate, cost effective procedure which is readily adaptable to a community hospital, provided that a pathologist with an interest in cytology is available.

Adolescent↗

Nonepithelial neoplasms arising within vesical diverticula.

Two cases of rare vesical tumors, a paraganglioma and a malignant fibrous histiocytoma, are reported. The occurrence of these tumors within the urinary bladder is rare; their occurrence within bladder diverticula appears unique. The clinical, radiologic, and pathologic findings are summarized.

Aged↗

A histochemical method for demonstrating papilloma virus infection in paraffin-embedded tissue.

In order to study the location of cells infected with human papilloma virus in paraffin-embedded tissues, the authors developed the following stain. Tissue sections were digested overnight with 0.01% deoxyribonuclease and then stained using the Feulgen stain with a light green counterstain. Cellular DNA was degraded, but viral DNA was not. Thus infected cells retained magneta nuclei, while uninfected cells stained a homogenous green. The stain was positive in 5/5 plantar warts, 7/8 verruca vulgaris, 2/2 laryngeal papilloma, and 18/20 condylomata accuminata. As a comparison, the indirect immunoperoxidase method on the same tissues stained 5/5 plantar warts, 6/8 verruca vulgaris, 0/2 laryngeal warts, and 2/20 condylomata accuminata. The presence of virus was confirmed by electron microscopic examination on one of the sections. Molluscum contageosum infected tissue also stained positively, but tissues infected with cytomegalovirus and herpes simplex virus did not. The only nonviral positive staining occurred with smears of sperm. The reasons for these results are discussed.

Animals↗

Genital condyloma virus infection following pelvic radiation therapy: report of seven cases.

Six women who underwent radiation therapy for gynecologic malignancies demonstrated cytologic evidence of condyloma virus infection 2 or more years following radiation. Histologic confirmation was obtained in two of the cases. A seventh patient developed in situ and invasive squamous cell carcinoma in a vulvar condyloma acuminatum following radiation therapy for Hodgkin's disease. This venereal infection is found most frequently in sexually active younger women (average age, 27 years). It is felt that depressed cell-mediated immunity consequent to the radiation therapy allowed the development of this infection in the older patients described in this report. The evolution of invasive squamous cell carcinoma in the condyloma acuminatum may indicate a possible oncogenic or cocarcinogenic effect of the virus. The immunologic responses to infection caused by the human papillomavirus group are discussed, as well as its potential for malignant transformation.

Adenocarcinoma↗

Cervical condylomatous atypia and its relationship to cervical neoplasia.

Seven hundred fifty-six consecutive cervical biopsy specimens were obtained for abnormal Pap smear results or abnormality on physical examination to determine the incidence of condylomatous atypia (CLA) and its association with true dysplasia (cervical intraepithelial neoplasia; CIN). Histopathologic criteria for the diagnosis of CLA and its distinction from CIN were developed and are defined and illustrated. Clinicopathologic evaluation disclosed (1) CLA is often overdiagnosed as dysplasia; (2) cervical CLA is often associated with CLN in the same patient and may represent a potential precursor lesion; (3) CLA occurs more frequently than CIN in younger patients; and (4) the mean age of patients with pure CLA is younger than combined CLA-CIN, which is in turn younger than individuals with pure CIN. The results of this study are evaluated in light of induced squamous carcinoma and in view of the known associated of condylomata and cancer of the external genitalia in humans. The results strongly indicate a need to examine the cervical CLA-CIN association with careful epidemiopathologic studies.

Adolescent↗