Premature rupture of membranes at term with an unfavorable cervix: comparison of expectant management, vaginal prostaglandin, and oxytocin induction.

BACKGROUND: Our objective was to determine the best treatment for parturients at term with an unfavorable cervix and premature rupture of membranes (PROM). METHODS: In this prospective study, 96 women with PROM and an unfavorable cervix were randomized into one of three treatment groups: oxytocin induction, vaginal prostaglandin E2 gel followed by oxytocin, or expectant management. RESULTS: Length of labor, cesarean section rate, and maternal/neonatal morbidity were not significantly different. In contrast, the interval from PROM until delivery and length of hospital stay were significantly longer in the expectantly managed group than in the other groups. Four of the patients who received expectant management required delivery because of nonreassuring fetal assessments. CONCLUSIONS: Expectant management of PROM at term significantly prolongs hospital stay without decreasing the incidence of abdominal delivery or infectious morbidity. There appears to be potential for cord compression in patients managed expectantly without continuous electronic fetal surveillance.

Advanced-stage small cell carcinoma of the ovary in pregnancy: long-term survival after surgical debulking and multiagent chemotherapy.

We report the longest disease-free survival achieved in an advanced-stage small cell carcinoma of the ovary. The patient had a stage IIIc tumor diagnosed during pregnancy. She underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and optimal tumor debulking. Following her immediate postoperative recovery, she was treated with a multiagent chemotherapy regimen with germ cell activity consisting of vinblastine, cisplatin, cyclophosphamide, bleomycin, doxorubicin, and etoposide. She is alive and without evidence of disease 5(1/2) years after diagnosis. This is the second reported case in pregnancy and the longest disease-free survivor of metastatic small cell ovarian carcinoma in the medical literature.

Ductal carcinoma in situ of the breast: reproducibility of histological subtype analysis.

Historically, two major strata of ductal carcinoma in situ (DCIS) have been linked to outcome, the presence or absence of comedo type and size. Our initial approach in classification was dichotomous, often favoring the comedo type with most worrisome implications to foster agreement in diagnosis. We have now tested guidelines that foster agreement in the modified Lagios three-tiered system. Sixteen cases of DCIS were selected, reflecting a spectrum of histological subtypes, with specific inclusion of cases in which consensus in classification using a dichotomous (comedo/noncomedo) scheme would be difficult. Six independent observers reviewed a minimum of five color 35-mm slides from each case at two separate occasions. The aim was to subclassify each case based on architectural pattern, nuclear grade, and presence or absence of tumor necrosis (Modified Lagios Classification, Lagios et al, Cancer 1989). After initial review, emphasizing placement of each case into a high- or low-grade category, there was disagreement in seven cases (44%), confirming our aim to choose cases with uncertain cues for classification. Agreement was achieved in 94% of cases by allowing re-review with emphasis on inclusion of an intermediate-grade category. Our study also suggests that pure micropapillary DCIS and apocrine DCIS warrant independent classification as "special type" DCIS. Our small pilot study suggests that, with adherence to specific criteria, most DCIS cases can be easily and consistently classified into the following five categories: (1) high grade, (2) intermediate grade, (3) low grade, (4) pure or predominantly micropapillary, and (5) pure apocrine. Our six observers independently reached a final concordance of 94% despite selection of cases in which consensus in a dichotomous classification was difficult. This was achieved predominantly by accepting an intermediate category of DCIS with intermediate nuclear features and limited necrosis. Confirmation of the applicability of the Modified Lagios Classification awaits completion of a much larger multi-institutional study in which statistical significance and interobserver variation can be better defined.

Extramammary Paget's disease of the vulva: metastases to the bone marrow in the absence of an underlying adenocarcinoma--case report and literature review.

A case of Paget's disease of the vulva is presented which, over a period of 6 years, was characterized by local recurrences and metastases to the bone marrow. Detailed examination of multiple sections of the primary tumor and of the bone marrow biopsy specimen failed to demonstrate an underlying adenocarcinoma in any of the sites. The routine histologic staining and immunohistochemical staining demonstrated that the metastatic cells strongly correlated with cells from the vulvar lesion. Specifically, immunohistochemical staining of the specimens from the primary and metastatic sites was positive for the gross cystic disease fluid protein-15, which has been associated with extramammary Paget's disease uncomplicated by underlying malignancies. Finally, during several years of close follow-up, no other primary site of Paget's disease declared itself clinically or was found by radiographic studies or analysis of serum tumor markers.

Continued local recurrence of carcinoma 15-25 years after a diagnosis of low grade ductal carcinoma in situ of the breast treated only by biopsy.

BACKGROUND: The stratification of ductal carcinoma in situ (DCIS) of the human breast into prognostically relevant categories by size and histologic pattern is a current concern. Few studies have been able to follow women after the identification of any type of DCIS when they have had biopsy only. METHODS: This is an extension of a follow-up study of a group of 28 women with small, noncomedo ductal carcinomas in situ that were excised by biopsy only, published in 1982. All these women have now been successfully followed for an average of almost 30 years. RESULTS: The overall risk of development of invasive carcinoma for these women over almost 30 years is nine times that of the general population (95% confidence interval, 4.7-17). This is similar to the 11-fold elevation in relative risk that was determined after about 15 years of follow-up. All invasive carcinomas have developed in the same area in the same breast. There were two women in whom invasive carcinoma developed between 20 and 30 years after initial biopsy. One other woman had an extensive noncomedo DCIS that was identified 25 years after her initial biopsy, but had no evidence of invasive disease. CONCLUSIONS: The natural history of small, noncomedo DCIS can last over at least 2 decades, with invasive carcinoma developing at the same site in which DCIS was previously discovered in a significant percentage of women (broadly, between 25%-50%). This is quite different from the natural history of comedo DCIS or any type of DCIS treated purposefully by surgery alone.

The Seattle children's bicycle helmet campaign: changes in helmet use and head injury admissions.

OBJECTIVE: To describe the impact of a community bicycle helmet campaign on helmet use and the incidence of bicycle-related head injuries. SETTING: Metropolitan community and a large health maintenance organization. INTERVENTIONS: Communitywide bicycle helmet campaign. OUTCOMES: Rate of observed bicycle helmet use in the community and incidence of bicycle-related injuries in an health maintenance organization population. RESULTS: Helmet use among school-aged children increased from 5.5% in 1987 to 40.2% in 1992. Bicycle-related head injuries decreased by 66.6% in 5- to 9-year-old and 67.6% in 10- to 14-year-old members of an health maintenance organization. CONCLUSIONS: Educational campaigns can increase helmet use and decrease the incidence of bicycle-related head injury.

Elderly persons' attitudes towards footwear--a factor in preventing falls.

Injuries from falls are the main cause of trauma morbidity that leads to mortality among the elderly. One prevention strategy is to wear sturdy shoes. This study was undertaken to determine the attitudes towards and use of sturdy shoes among older adults. A random sample of persons ages 65 years and older was contacted by phone; 652 completed interviews. Sturdy shoes were worn by 26 percent of persons at the time of the call; more than two-thirds reported wearing such shoes at some time. Barriers to use of sturdy shoes included foot problems, difficulty putting them on, expense, style, and lack of knowledge about their importance. There was no difference in shoe use by the respondents' history of previous falls. The results provide information useful in the development of a program to increase the use of sturdy shoes by this population.

Lobular neoplasia of the breast: higher risk for subsequent invasive cancer predicted by more extensive disease.

We have stratified the cancer risk implications of lobular pattern in situ neoplasias of the breast by separating marked examples of this histologic spectrum (lobular carcinoma in situ [LCIS]) from lesser examples (atypical lobular hyperplasia). The lesser-developed examples have been shown previously to have a lower relative risk (RR) of later invasive carcinoma of the breast (IBC). Forty-eight examples of LCIS were found in 10,542 otherwise benign breast biopsies, representing an incidence of 0.5%. Nine patients were excluded from follow-up because of bilateral mastectomy within 6 months of entry biopsy, IBC within 6 months of entry biopsy, or prior IBC. Follow-up of the remaining 39 patients was complete, averaged 18 years, and revealed an RR of subsequent IBC of 6.9 (P less than .00001). Average overall follow-up for LCIS patients was 19 years; it was 25 years for those alive and free of IBC at the time of their follow-up interview. Neither family history of IBC nor postmenopausal estrogen therapy further affected risk. The absolute risk of IBC after LCIS was 17% at 15 years (adjusted for withdrawals), and the RR was 8.0 in the first 15 years of follow-up compared with the general population. An analysis based on a time-dependent hazards model found that during the first 15 years following biopsy women with LCIS had 10.8 times the risk of breast cancer compared with biopsied women of comparable age who lacked proliferative disease. Some previously published articles reporting lobular neoplasia (LN) suggest that those series with the greatest incidences of LN (whether termed LN or LCIS) have the lowest RR of subsequent breast cancer. Those series with higher incidences of LN include less well-developed histologic patterns of LN (atypical lobular hyperplasia). We conclude that our study of LN and studies performed by others support the higher risk of IBC after histologically flagrant examples (LCIS, about nine times higher) and a relatively lower but definable risk after more histologically subtle examples (atypical lobular hyperplasia, four to five times lower). This relative cancer risk is probably not constant over more than 15 years; thus, cancer risk 15 to 25 years after initial diagnosis of LCIS is uncertain.

Prevention of pedestrian injuries to children: effectiveness of a school training program.

Pedestrian injuries are a complex problem for which no single intervention will be completely effective. One component of a community-wide program, training of schoolchildren in street-crossing skills, is evaluated. The program targeted public school students in grades K through 4 with an eight-session training program by a single teacher, cross-age teaching, videotape feedback, and in 1990 parent-child activity workbooks. Children's street crossing was observed pretraining and posttraining and graded on four behaviors: WALKING on sidewalk/shoulder vs in the street; STOPPING at the curb; LOOKING L-R-L before crossing; KEEP LOOKING while crossing. Analysis was conducted on matched pairs in which observations pretraining were compared with those posttraining on same child. Observations were completed on 137 children in 1989 and 92 in 1990. Nearly all children walked on the side of the road; however, fewer than 50% of children STOPPED, 25% LOOKED, and fewer than 20% KEPT LOOKING before training. Training did not improve the performance on the first two behaviors in either year, significantly increased LOOKING in 1990, and increased KEEP LOOKING by twofold in 1989 and threefold in 1990. It is concluded that pedestrian skills of children can be improved but that such a program must be part of a broader effort if pedestrian injuries are to decrease.

The Seattle children's bicycle helmet campaign.

Though bicycle head trauma is a significant cause of mortality and morbidity, much of which can be mitigated by wearing protective helmets, in 1986, few schoolchildren in the area of Seattle, Wash, were observed to wear helmets. We describe the mechanics of a multifaceted campaign undertaken to alter this situation, involving a coalition of health, bicycle, and helmet industry organizations. These were the major objectives: (1) to convince parents that riding bicycles without helmets is hazardous, (2) to lower the price of helmets to more affordable levels, and (3) to overcome the reluctance of children to wear helmets. The campaign was successful; the sales of one brand of a youth helmet in the Seattle area rose from 1500 to 22,000 over a 3-year period, and the observed helmet usage rate among school-age children increased from 5% to 16% compared with a rise of only 1% to 3% in a control community, Portland, Ore.

Effects of systemically administered monoamine reuptake blocking agents on patterns of buspirone-induced analgesia in rats.

We have recently shown the serotonin 5-HT1A receptor agonist buspirone to produce analgesia in several pain tests in rats. As a 5-HT1A agonist, buspirone may change serotonergic (5-HT) tone to alter the balance of central monoaminergic (MA) systems that function in analgesia. MA-reuptake blocking drugs have been shown to produce analgesia, both when given alone and in combination with a variety of other agents, presumably via their action upon MA neurochemistry. The present study was undertaken to examine the effect of systemic administration of the 5-HT-reuptake blocker amitriptyline (AMI: 10 mg/kg), NE-reuptake blocker desipramine (DMI: 10 mg/kg) or DA-reuptake blocker GBR-12909 (7.5 mg/kg) on patterns of analgesia produced by buspirone (1-5 mg/kg) in thermal and mechanical pain tests in rats. Neither reuptake blocking agents or buspirone, when administered alone or in combination, produced overt changes in motor activity at the doses tested. AMI alone was not analgesic in either thermal or mechanical pain tests. In both assays, AMI reduced the analgesic action of buspirone, with greater effects seen in the thermal test. When administered alone, DMI produced significant analgesia against thermal and mechanical pain. DMI significantly attenuated the analgesic action of all doses of buspirone in both pain tests. Alone, GBR-12909 did not affect nociception in thermal or mechanical tests. GBR-12909 decreased buspirone-induced analgesia at all doses in the thermal test, while having no effect on buspirone-induced analgesia against mechanical pain. These results demonstrate that facilitation of 5-HT, NE and DA function with reuptake blocking drugs did not enhance the analgesic action of buspirone. These data indicate against the adjuvant use of reuptake blocking compounds and buspirone as analgesics. Furthermore, such findings may suggest other possible non-MA substrates of buspirone-induced analgesia.

Invasive breast cancer risk in women with sclerosing adenosis.

To assess sclerosing adenosis (SA) as an independent risk factor for subsequent invasive breast cancer (IBC), the authors reviewed 10,366 benign breast biopsy specimens (BB) obtained between 1950 and 1968 and identified 547 cases of SA meeting strict histologic criteria of expanded lobular units with whorled compressed acini. Of those women targeted for follow-up (3303, of whom 349 had SA), 84% were successfully followed for an average of 17 years. The relative risk for IBC among patients with SA regardless of the presence of atypical hyperplasia (AH) was 2.1. This risk decreased to 1.7 when patients with AH were excluded, and rose to 6.7 when only those patients with SA and AH were analyzed. The coexistence of a family history of IBC in a first-degree relative did not further elevate risk above that of SA alone when women with AH were excluded. Sclerosing adenosis was found to be positively associated with atypical lobular hyperplasia (ALH) as ALH was present in biopsy specimens with SA 2.7 times more frequently than in other biopsy specimens. Perimenopausal age, histologic calcification, and family history of IBC (FH) were also positively associated with SA. Sclerosing adenosis was most frequent in the perimenopausal period and had a weak association with family history of IBC. No association with atypical ductal hyperplasia (ADH) was identified. The authors conclude sclerosing adenosis represents an independent risk factor for subsequent invasive breast cancer apart from its association with ALH, and the risk (excluding patients with coexistent atypical hyperplasia) is in the range of 1.7, times thereby justifying inclusion of sclerosing adenosis as a component of a group of histopathologically defined lesions termed "proliferative breast disease without atypia" which implies a relative cancer risk of 1.5 to 2.0.

Influence of exogenous estrogens, proliferative breast disease, and other variables on breast cancer risk.

The authors reevaluated 10,366 consecutive breast biopsy specimens of benign lesions performed between 1950 and 1968. Follow-up information was obtained on 3303 women with a median duration of follow-up of 17 years. This sample contained 84% of the patients originally selected for follow-up. The relative risk (RR) of developing breast cancer was 0.98 for women who took exogenous estrogens as compared to 1.8 for women who did not. Exogenous estrogens lowered the observed breast cancer risk in women with atypical hyperplasia (RR = 3.0 versus 4.5), proliferative disease without atypia (RR = 0.92 versus 1.9), and in women without proliferative disease (RR = 0.69 versus 0.91). Women who took estrogens before 1956 were at 2.3 times the risk of other estrogen users, presumably due to a dose effect. There was no significant association between breast cancer risk and birth control pills, cigarette smoking, or alcohol consumption. Exogenous estrogens are not associated with increased breast cancer risk in women with benign breast disease. A previous history of benign breast disease does not contraindicate replacement estrogen therapy.

Ductal involvement by cells of atypical lobular hyperplasia in the breast: a long-term follow-up study of cancer risk.

A cohort study of women with ductal involvement by cells of atypical lobular hyperplasia (DIALH) revealed an incidence of 1.4% in benign biopsy specimens. When combined with diagnostic lobular unit alterations of atypical lobular hyperplasia (ALH), a consequent risk of invasive carcinoma of 6.8 times that in the general population was found. This relative risk for women with ALH and DIALH approaches the risk for lobular carcinoma in situ, whereas the risk for ALH with or without DIALH is 4.3 and the risk for ALH without DIALH is reduced to 2.7. Only definitive changes of DIALH with an insinuated characteristic population of cells between attenuated luminal cells and basement membrane should be so diagnosed. DIALH in association with lobular alterations that are borderline with regard to a diagnosis of lobular carcinoma in situ will increase the certainty that a medically meaningful increased risk for subsequent invasive cancer is indicated.

Breast cancer risk of lobular-based hyperplasia after biopsy: "ductal" pattern lesions.

Three thousand three hundred three women were followed an average of 17 years following benign breast biopsy. These women comprise 84.4% of those originally targeted for follow-up. Risk of invasive breast cancer development was analyzed in relation to the hyperplasia classification scheme of Wellings et al (JNCI 1975; 55:231-73) that is based on terminal ductal-lobular units (ALA). Cancer risk was also assessed with respect to family history of breast cancer in first-degree relatives (FHBC), as well as atypical features of hyperplasia recognized by resemblance to carcinoma in situ of ductal type (ADH). There was a trend of increasing cancer risk with increasing degree of ALA lesion, reaching 1.9 with ALA-IV lesions having both qualitative and quantitative features of advanced atypical hyperplasia. When ADH lesions are removed from the analysis, any predictive power of ALA lesions is lost. ADH recognizes histologic lesions with a four- to fivefold increased risk of breast cancer. FHBC interacts with any hyperplastic lesion so as to approximately double the cancer risk.

Atypical hyperplastic lesions of the female breast. A long-term follow-up study.

A total of 10,542 breast biopsy specimens obtained between 1950 and 1968 were studied. Examples of atypical "ductal" (ADH) and atypical lobular hyperplasia (ALH), defined as having only some features of carcinoma in situ (CIS), were diagnosed in 3.6% of these specimens. In the same series, CIS was diagnosed in 1.7% of biopsy specimens excluding those with invasive cancer. The subsequent risk of invasive breast carcinoma after ALH or ADH was 4-5 times that of the general population. Follow-up was 90% successful and extended 17 years after biopsy. History of breast cancer in a mother, sister, or daughter doubled the risk of subsequent invasive carcinoma development (to 8 times for ALH and 10 times for ADH). The authors conclude that among the epithelial hyperplastic lesions of the human breast, a minority may be recognized by their resemblance to CIS which have a clinically significant elevation of subsequent breast cancer risk. This risk is one-half that of CIS.

Intraductal carcinoma of the breast: follow-up after biopsy only.

Twenty-eight women with ductal carcinoma in situ (DCIS) of the breast treated by biopsy only were identified in a histologic review of 11,760 biopsies performed between 1950 and 1968. Seven of the 25 women followed for more than three years developed invasive breast carcinoma, all in the same breast with a previously detected DCIS. Average follow-up interval for the 18 women not developing invasive carcinoma was 16 years. The invasive carcinomas presented clinically from three to ten years (average, 6.1) after the biopsies demonstrating DCIS. Four women with invasive carcinoma developed distant metastases following mastectomy. This study suggests that 28% of women treated with biopsy only for DCIS presenting as an incidental histologic finding will develop invasive carcinoma in a follow-up period of approximately 15 years.