Cancer risk in diethylstilbestrol-exposed offspring

The occurrence of columnar epithelium in the vagina (vaginal adenosis) in young women with intrauterine exposure to diethylstilbestrol (DES) during the first trimester of pregnancy was observed in 231 patients (82 per cent of 280 cases who underwent colposcopic study). Extension of columnar epithelium onto the portio of the cervix was present in the remaining 18 per cent of the cases. Abnormal colposcopic findings were present in the transformation zone in 96 per cent of the patients with vaginal adenosis. Directed biopsy revealed four cases of vaginal and/or cervical squamous carcinoma in situ (CIS), two cases of severe dysplasia, five cases of moderate, and 29 cases of mild dysplasia. The prevalence of CIS in DES-exposed girls (1.4 per cent) was nearly five times the prevalence rate of CIS in a control group of 5,808 DES-unexposed women (0.44 per cent). This finding correlates well with the hypothesis that the genesis of squamous intraepithelial neoplasia is specifically related to the extent and surface area of the vaginal transformation zone. An unusual case of invasive squamous carcinoma in a DES-exposed young girl is presented, which represents the initial observation of this association to date.     

Comparing two modalities of management of women with cytologic evidence of squamous or glandular atypia: early repeat cytology or colposcopy

Early repeat cytology is recommended in most screening programs for cervical cancer in subjects with squamous or glandular abnormalities not amounting to neoplasia (atypical squamous cells of undetermined significance, ASCUS), but immediate colposcopy is also recommended in some countries, especially those where there is easy access to colposcopic facilities. We evaluated the cost-effectiveness of the two procedures in a prospective study of women with cytologic ASCUS, invited to cytocolposcopic assessment after 6 months. Colposcopy-directed biopsy was assumed as the gold standard, and the accuracy of colposcopy at 6 months was assumed to be equal to that of immediate colposcopy. Out of 874 compliers, punch biopsy was performed in 303 cases (34.7%), and 19 CIN2+ lesions were detected (CIN2 = 12, CIN3 = 6, microinvasive carcinoma = 1). Detecting 13 CIN2+ lesions at colposcopy required 874 colposcopies and 303 directed biopsies: the cost per CIN2+ lesion detected with the procedure was 2,749 US$. Detecting 15 CIN2+ lesions at repeat cytology required 874 cytologic examinations, 137 colposcopies, 64 directed biopsies, and 6 diagnostic large-loop resections, the latter being performed in subjects with high-grade squamous intraepithelial lesion and less severe lesions at punch biopsy: the cost per CIN2+ lesion detected with the procedure was 1,961 US$. The policy of repeat smear was more cost-effective than immediate colposcopy. According to such results, the protocol of the Florence screening program has been modified since October 1996.     

Genital intraepithelial lesions in immunosuppressed female patients after renal transplant: cytologic, colposcopic, and histologic study

Twenty seven female patients immunosuppressed after renal transplantation were studied. Cytological, colposcopic and histologic studies of biopsies were used to determine the incidence of neoplastic intraepithelial lesions and those due to infection by human papilloma virus. Intraepithelial neoplasia was found in 7.4% and papilloma virus infection in 60%. Cervix cytology was insensitive (33%) for diagnosis of intraepithelial lesions. Therefore, cytology and colposcopy are recommended for routine follow up of immunosuppressed women.     

Effects of acetysal, dexamethasone and their combination on drug metabolizing enzyme systems in rat liver microsomes

One hundred and sixty-eight cases of cervical conization were performed for cervical intraepithelial neoplasia (CIN) in a 32-month study. The indications for conization were unsatisfactory colposcopic finding, abnormal epithelium that extended into the endocervical canal, a microinvasive cervical cancer, and significant discrepancy among cytology, colposcopy, and/or punch biopsy histology. In the early period of the study, conization was done by the cold-knife method (N = 107), whereas loop diathermy was used in the latter part of the study (N = 61). Both groups were similar in terms of age, indications for conization, and size of cervical cone specimens. Loop diathermy conization was done in a significantly shorter time (5.7 +/- 1.8 minute vs 15.2 +/- 6.1 minute)(P < 0.05) than cold-knife conization. However, the difference in the postoperative complications between loop diathermy(3.0%) and cold-knife conization(4.7%) was not significant. The incidence rate of residual CIN III lesions in the subsequent hysterectomy specimens, found by histological documentation on these specimens was 25.0 and 26.1 percent after loop diathermy and cold-knife conization respectively. These results suggest that loop diathermy is much easier to perform and a more time-conserving treatment modality than cold-knife conization in the management of patients with cervical intraepithelial neoplasia.     

Cervical intraepithelial neoplasia in HIV seropositive patients

In order to assess the frequency of cervical intraepithelial neoplasia (CIN) in a high risk population, 32 women infected with human immunodeficiency virus (HIV), with no AIDS-related symptoms, underwent colposcopic, cytologic and histologic examinations of the uterine cervix. In seven cases (21.9%) cervical smears showed dysplasia and in nine cases (28.1%) histologic evaluation indicated CIN. No invasive carcinomas were observed. In seven of the nine women CIN was associated with lesions due to human papillomavirus infection (HPV). These data confirm that HIV-positive women are at increased risk for developing neoplasias in the lower genital tract and are in need of regular and careful cytologic and, in particular, colposcopic and histologic examinations.     

Human papillomaviruses and carcinogenesis of the uterine cervix: future prospects in the domain of detection and prevention

It is now admitted that certain genotypes of human papillomavirus (HPV), mainly HPV types 16 and 18, play an etiological role in the origin of the great majority of invasive carcinomas of the uterine cervix and their intraepithelial precursors. Such an evidence has modified our understanding of the natural history of cervical cancer and should result in new approaches for the early diagnosis and prevention of precursor lesions. Sensitive, specific and reliable HPV detection tests have been progressively designed but their use as routine tests requires multicentric studies, involving large series of women, to evaluate their usefulness in the clinical management or the screening of patients and to establish their limits and cost-effectiveness. It is already most likely that the association of HPV detection tests to cervicovaginal cytology would increase the detection rate of high-grade intraepithelial neoplasia and constitute a means for quality control in cytology. The viral origin of most cancers of the uterine cervix paves the way for their prevention by vaccination against the main oncogenic HPV genotypes and provides hope for specific immunotherapy of associated neoplasia.     

Vaginal and cervical squamous cell dysplasia in women exposed to diethylstilbestrol in utero

Two hundred and fifty patients were examined because of a history of in utero exposure to diethylstilbestrol (DES) or because of the presence of physical findings suggesting such exposure. One thousand biopsies were examined for the presence of neoplasia and then compared to the colposcopic findings. There were no cases of glandular or squamous cell carcinoma. Fifteen (6 per cent) of the patients had squamous cell dysplasia. The degree of dysplasia was mild in 11 and moderate in only 4 (1.6 per cent) of the women. The majority of the cases of dysplasia involved the cervix, whereas the vagina was involved in only four cases, with simultaneous cervical dysplasia in three of these. Patients with cervical mosaic and white epithelium had dysplasia on biopsy much more frequently as compared with patients with similar colposcopic appearances in the vagina. Our results suggest a low incidence of significant squamous precancerous change in the DES-exposed population and provide evidence that colposcopic data concerning dysplasia pertinent to the cervix cannot be applied without modification to the evaluation of dysplasia in vaginal adenosis.     

Radiotherapy of humero-scapular periarthritis using ultra-hard photons. Evaluation by MRI findings

OBJECTIVE: To determine the clinical implications of atypical glandular cells of uncertain significance (AGCUS) in cervical cytologic smears. STUDY DESIGN: Retrospective analysis. RESULTS: Eighty-eight of 32,181 (0.27%) cervical smears obtained during the study period contained AGCUS. Of the 47 women with AGCUS, 16 had intraepithelial or invasive neoplasms (34%; 95% confidence interval, 21-49%), including 9 low or high grade squamous intraepithelial lesions, 1 adenocarcinoma in situ of the cervix, 3 adenocarcinomas of the cervix, 2 adenocarcinomas of the endometrium and 1 adenoid basal cell carcinoma of the cervix. CONCLUSION: The high prevalence of cervical and endometrial neoplasia among women with the isolated finding of AGCUS on cervical cytologic smears warrants a thorough diagnostic evaluation.     

Notifying women of the results of their cervical smear tests by mail: does it result in a decreased loss to follow-up of abnormal smears?

We undertook a prospective randomised intervention study of the proportions of women with abnormal cytology results who were lost to follow-up in 42 general practices in urban and rural Queensland over 26 weeks. Practices in the intervention group were provided with a redesigned cervical smear request form that allowed patients to provide an address for direct notification from the laboratory by mail. Satisfaction questionnaires sent to the general practitioners in the intervention group showed that most made at least some use of direct notification, and most felt it was worthwhile. For women with an initial result of cervical intraepithelial neoplasia (CIN), there was a loss to follow-up of 23 per cent (95 per cent confidence interval (CI) 11 to 39) among the control group compared to none in the intervention group (upper CI 7 per cent), a highly significant difference (P < 0.001). Mailing cervical screening results to women may reduce the loss to follow-up of those with CIN findings.     

Intraepithelial neoplasia of the vulva

Intraepithelial neoplasia of the vulva is being seen with increasing frequency. Awareness of this should prompt the clinician to carefully inspect the vulva on all patients. Reports strongly suggest a relationship between infection with human papillomavirus and vulvar intraepithelial neoplasia. The frequency with which this disease progresses to invasive carcinoma is unknown at present. However, it is obvious that it does occur. Both the warty and basaloid types of vulvar intraepithelial neoplasia are associated with HPV infection and are often associated with invasive squamous cell carcinoma of the vulva demonstrating similar morphologic characteristics. These changes are seen more often in younger women who smoke than in the older nonsmoking woman whose lesions do not appear to be HPV related. Both local excision and the carbon dioxide laser are effective for treating vulvar intraepithelial neoplasia. The choice of which approach to take depends upon the location and size of the lesion or lesions. Whichever approach is utilized, preservation of the normal vulvar anatomy and function are of paramount importance.     

Endoscopic ultrasonography for preoperative staging of esophageal carcinoma

OBJECTIVE: The objective was to determine the frequency with which regression or progression of disease without treatment occurred in women diagnosed with squamous cell cervical carcinoma in situ (CIS) during pregnancy. METHODS:. A retrospective chart review of all women evaluated at the University of Iowa Colposcopy Clinic diagnosed with CIS during pregnancy from 1987 through 1992 was used. Thirty-four women were evaluated during pregnancy, of which 26 also had postpartum evaluation. All pathology reports of initial cytology and biopsies, as well as colposcopic impressions, were reviewed and compared to the same evaluations postpartum. RESULTS: Of the 26 women evaluated both antepartum and postpartum, only 1 was treated (cone biopsy) during pregnancy. She had disease suspicious for microinvasion. She was disease free postpartum. Of the remaining 25, 20 (80%) had persistent disease, 2 (8%) had either missed disease or progressive disease postpartum, and 3 (12%) resolved without treatment at postpartum evaluation. No statistical significance was found between route of delivery and persistence (P = 0.34). No statistical significance was found between smoking and persistence of disease (P = 1.0). In 46% of women the initial cytology was CIN I or II, and the initial colposcopic impression was found to underestimate the severity of the disease in 35% of cases. Two women were found to have invasive disease postpartum. CONCLUSIONS: There is a high persistence rate of CIS complicating pregnancy. Given the relatively high rate of underestimation of disease severity by both cytology and colposcopic impression, the use of routine biopsy at the time of colposcopy is recommended. Invasive disease may be encountered on postpartum evaluation.     

Utility of fine-needle aspiration cytology and frozen-section examination in the operative management of thyroid nodules

Fine-needle aspiration cytology has a high sensitivity for the diagnosis of solitary thyroid nodules. Certain diagnoses involving follicular histologies often cannot be made with needle biopsy alone. The utility of frozen-section examination of thyroid nodules, with particular regard to those lesions with follicular histologies, is also limited. We examined the correlation of fine-needle aspiration cytology and frozen-section examination in solitary thyroid nodules to determine the contribution of frozen-section examination to the operation. We reviewed the fine-needle aspiration cytology, frozen-section examination, and final pathology of 100 consecutive patients undergoing thyroidectomy for a solitary solid thyroid nodule in an 4-year period. The diagnoses were classified as indeterminant, benign, or malignant. The utility and impact of the diagnosis from fine-needle aspiration or frozen section on the operative procedure performed was analyzed. Fine-needle aspiration cytology as a diagnostic test for thyroid nodules demonstrated an indeterminant rate of 23 per cent, with a diagnostic accuracy of 77 and 92 per cent for benign and malignant disease, respectively. In all patients with inaccurate benign diagnosis on fine-needle aspiration cytology, follicular neoplasm was misinterpreted for follicular adenoma or multinodular goiter. In comparing frozen-section results, the indeterminant, benign, and malignant rates were 7, 96, and 64 per cent, respectively. Of the 23 patients with indeterminant results on fine-needle aspiration cytology, the intraoperative frozen-section diagnosis on 4 patients was deferred to permanent section; 18 received accurate cytological diagnosis; and in 1 patient, carcinoma was missed. Overall, the decision about the extent of surgical thyroid resection was changed in only 2 patients based on the frozen-section results. Preoperative evaluation with fine-needle aspiration cytology can accurately and appropriately define the extent of thyroid surgery in most patients with a diagnosis of malignant neoplasm or benign disease. Intraoperative frozen-section examination may be helpful if fine-needle aspiration cytology results are inderminant and in cases of follicular histology as an adjunct for evaluation of the thyroid nodule, but overall, frozen section does not contribute to the management of the thyroid lesion at the time of surgery.     

2-(4-Aminophenyl)benzothiazoles: novel agents with selective profiles of in vitro anti-tumour activity

OBJECTIVE: To evaluate the results of cervical cytology screening in the National Breast and Cervical Cancer Early Detection Program and to compare the findings with results from other screening programs. METHODS: We analyzed data on 312,858 women aged 18 years and older who received one or more Papanicolaou smears, and follow-up if indicated, from October 1991 through June 1995 at screening sites across the United States providing comprehensive National Breast and Cervical Cancer Early Detection Program services. RESULTS: Of the women screened, more than half were 40 years or older; slightly less than half (44%) were of racial and ethnic minorities. During the first screening cycle, 3.8% of Papanicolaou tests were reported as abnormal (squamous intraepithelial lesion [SIL] or squamous cell cancer); proportions of abnormals decreased with increasing age. The age-adjusted rate of biopsy-confirmed cervical intraepithelial neoplasia (CIN) II or worse among women screened was 7.4 per 1000 Papanicolaou tests; rates of CIN were highest among young women, but cancer rates peaked among women in their 50s and 60s. The percentages of first screening cycle-Papanicolaou tests interpreted as high-grade SIL and squamous cell carcinoma associated with biopsy-confirmed CIN II or worse (the positive predictive value) were 56.0% for CIN II/III and 3.7% for invasive cancer. Of the 150 invasive cancers diagnosed, 54.0% were classified as local disease. CONCLUSION: Observed results emphasize the duality of cervical neoplasia-CIN in younger women and invasive cancer in older women. This finding points to the importance of reaching both younger and older women for cervical cancer screening.     

Immunohistochemistry with antibody to the LA-1 oncogene as a prognostic marker in cervical intraepithelial neoplasia

Previous studies with antibody to a synthetic peptide designated LA-1 identified a 60-kDa protein in cervical intraepithelial neoplasia and invasive cancer tissues. To determine whether these findings are of clinical significance cervical tissues from 223 patients with squamous intraepithelial lesion (SIL) or invasive carcinoma and 39 normal healthy cervical tissues were stained with antibody to LA-1 using the immunoperoxidase assay. Tissues from 52 patients with squamous carcinomas at other sites were used as controls. Staining was respectively observed in 46.4, 56.5, and 64.7% of patients with low-grade SIL, high-grade SIL, and invasive cancer. It was localized in the atypical epithelium involving a progressively larger extent of epithelium as a function of increased pathologic grade. Only 10.3% of the normal cervical tissues stained with anti-LA-1 antibody. Twenty-five patients that were lost to follow-up for 2-5 years after the original diagnosis were studied at the time of diagnosis (1 degree biopsy) and when they returned to the clinic (2 degrees biopsy). In the follow-up series, LA-1 staining was observed in both biopsies from 9/12 patients that progressed to a higher degree of atypia, while 9/11 patients whose lesions remained stationary were LA-1 negative. Our studies suggest that LA-1 might be a useful biological marker of cervical neoplasia.     

Significance of a first-time atypical Papanicolaou smear in a young, high-risk African-American and Latino-American population

The first atypical Papanicolaou smear in young, sexually active Latino and African-American women of low socioeconomic status may be predictive of underlying cervical neoplasia and human papillomavirus infection of significant quantity. The optimal management of first-time atypia on routine Pap smear has not been established. In many clinics, colposcopically directed sampling of the cervix is recommended only if atypia persists following specific or nonspecific treatment of cervicitis or after an arbitrarily determined time interval. Others recommend immediate colposcopic evaluation. To determine the best approach to the first-time atypical Pap smear in young minority women at high risk for the development of cervical cancer, 250 such patients were evaluated with colposcopically directed biopsy of the cervix prior to any form of therapy. Pap smears were repeated at the time of colposcopy. Histologically, there was evidence of cervical intraepithelial neoplasia in 41% of patients and human papillomavirus infection in 86%. Repeat Pap smears predicted the presence of cervical intraepithelial neoplasia in only 24% of patients. Immediate colposcopic evaluation represents the most prudent approach to the first-time atypical Pap smear in young, high-risk minority women.     

The management of DES-exposed women: one physician's approach

The female offspring of DES-treated mothers are examined cytologically and colposcopically annually, starting at the age of seven years no treatment is indicated until a colposcopic atypical transformation zone occurs. With its occurrence all the abnormal epithelium(squamous or columnar) is excised from the vagina and cervix under colposcopic guidance in the hospital or in the office under local anesthesia. The procedures are done in stages to minimize scarring and to eliminate the possibility of vaginal-cervical adhesions or vaginal shortening. The finding of an incidence of 47% of cervical or vaginal intraepithelial neoplasia in 34 patients aged 10 to 26 years so treated to date indicates a high risk of potential candidacy for squamous carcinoma of the vagina or cervix in later years.     

Colposcopic evaluation of pregnant patients with abnormal cervical smears

Colposcopic examination and biopsy were used to assess 123 pregnant patients presenting with abnormal cervical smears. Eighty-seven per cent were 30 years of age or less and 95 (77 per cent) had had one or no previous children. Two patients were found to have microinvasive carcinoma and, in an additional 95 patients, either severe dysplasia or carcinoma in situ was present. Fifty-five patients (45 per cent) had subsequent conization or hysterectomy and in no instance was the histological diagnosis more serious than that anticipated from the colposcopic evaluation. Only three patients (1-6 per cent) had a cone biopsy during pregnancy; only one minor complication occurred. Colposcopic examination is the choice method of evaluating patients with abnormal cervical smears in pregnancy.     

Localization of the APECED protein in distinct nuclear structures

The effect of changes in cytology laboratory costs, including the costs of new technologies, on the cost-effectiveness of cervical cancer prevention has not been studied. Using University of Iowa laboratory detection rates and costs, a decision model determined the cost-effectiveness of the laboratory with and without new technologies. Compared with not performing a cervicovaginal smear, the cost to increase the discounted life expectancy per patient by 1 year was $2,805 for the laboratory component alone and $19,655 for the entire cervical cancer prevention strategy. In moderate- to high-risk women, cervical cancer screening was cost-effective even at high cytology laboratory costs (eg, $75 per smear). New technologies were cost-effective only if they resulted in a substantial increase in the detection of high-grade squamous intraepithelial lesions (eg, an additional 236 high-grade squamous intraepithelial lesions per 10,000 women). New technologies have not demonstrated these increased detection rates.     

Management of cervical neoplasia with colposcopy

During a 44-month period the introduction of colposcopy to a metropolitan dysplasia clinic resulted in 1, 144 colposcopic examinations on 442 patients. Agreement between colposcopically directed biopsy and final diagnosis was found in 84%, and directed biopsy revealed the most advanced lesion in 42.5%. Satisfactory colposcopy was performed on 93% of patients, and some degree of histologic abnormality was obtained in 86% of patients with colposcopic abnormalities. Undetected invasive cervical cancer occurred in both cervical conization and colposcopic examinations with equal frequency. Endocervical curettage detected two cases of occult invasive cancer, and increased use of this procedure is recommended. Guidelines for management of cervical neoplasia are suggested.