Kimberly A. Roehl

Serial Biopsy Results in Prostate Cancer Screening Study

PURPOSE We evaluated prostate biopsy results in men with elevated prostate specific antigen (PSA) levels and/or suspicious digital rectal examination whose initial biopsies did not reveal cancer. MATERIALS AND METHODS A total of 2,526 volunteers 40 years old or older underwent 1 or more prostate biopsies for serum PSA concentrations greater than 4.0 ng./ml. (before May 1995) or greater than 2.5 ng./ml. (after May 1995), or digital rectal examination suspicious of cancer. We evaluated compliance with the biopsy recommendation and the cancer detection rate with regard to digital rectal examination results and increasing PSA levels. RESULTS Of the men who underwent up to 10 biopsy procedures the serial cancer detection rates were 29%, 17%, 14%, 11%, 9% and 7%, respectively, on biopsy procedures 1 through 6. No significant difference in the yield of cancer on serial biopsies was observed between the groups using the greater than 4.0 ng./ml. and greater than 2.5 ng./ml. cutoff. There was a trend for more cancers detected through serial screening to be organ confined compared with those detected on initial screening (78% versus 69%, p = 0.05). Also, more cancers detected using the greater than 2.5 ng./ml. cutoff were organ confined (80% versus 66%, p = 0.004). Only approximately 1% of the cancers fulfilled the published criteria for clinically insignificant tumors. CONCLUSIONS Nearly a quarter of prostate cancers detected in this screening study were missed by the initial biopsy. Of the 962 prostate cancers detected 77% were detected with 1, 91% with 2, 97% with 3 and 99% with 4 biopsy procedures. Serial biopsies detect more organ confined cancers without over detecting clinically unimportant tumors. Future studies are needed to determine whether obtaining more biopsy cores initially would provide earlier prostate cancer detection and avoid unnecessary repeat biopsies.

Identification of intracellular bacteria in the basal plate of the human placenta in term and preterm gestations

OBJECTIVE Bacteria have been identified in different regions of the placenta. Here, we tested the hypothesis that the maternal basal plate of the placenta harbors microbes that may be associated with adverse pregnancy outcomes. STUDY DESIGN We performed a cross-sectional study of pregnancies from a single tertiary care hospital. Maternal medical and obstetric characteristics were obtained and pregnancies followed up prospectively for outcomes and placental collection. After delivery, systematic random sampling of the placental basal plate was performed. Paraffin sections of basal plates were stained with 4 histologic stains and scored for morphological evidence of bacteria. RESULTS Of 195 total patients in the study, Gram-positive and -negative intracellular bacteria of diverse morphologies were documented in the basal plates of 27% of all placentas. Of the patients, 35% delivered preterm. No difference was noted between placental basal plates from preterm or term gestations. Intracellular bacteria were found in the placental basal plates of 54% spontaneous preterm deliveries <28 weeks, and in 26% of term spontaneous deliveries (P = .02). Intracellular bacteria were also documented in placentas without clinical or pathologic chorioamnionitis. CONCLUSION A total of 27% of placentas demonstrated intracellular bacteria in the placental basal plate using morphological techniques. Thus, the maternal basal plate is a possible source of intrauterine colonization and placental pathological examination could include examination for bacteria in this important maternal-fetal interface.

Identifying Patients at Risk for Significant Versus Clinically Insignificant Postoperative Prostate-Specific Antigen Failure

PURPOSE We evaluated whether men at risk for significant versus clinically insignificant prostate-specific antigen (PSA) failure after radical prostatectomy could be identified using information available at diagnosis. PATIENTS AND METHODS A prospective prostate cancer screening study that enrolled, diagnosed, and treated 1,011 men with radical prostatectomy at Barnes-Jewish Hospital (St Louis, MO) from January 1, 1989, to June 1, 2002, for localized prostate cancer formed the study cohort. Preoperative predictors of a postoperative PSA doubling time (DT) of less than 3 months and more than 12 months or no PSA failure were identified using logistic regression. RESULTS A preoperative PSA velocity more than 2.0 ng/mL/yr (P = .001) and biopsy Gleason score 7 (P = .006) or 8 to 10 (P = .003) were significantly associated with having a postoperative PSA DT less than 3 months. A PSA level less than 10 ng/mL (P = .005), a nonpalpable cancer (P = .001) with a Gleason score < or = 6 (P = .0002), and a preoperative PSA increase that did not exceed 0.5 ng/mL/yr (P = .03) were significantly associated with a postoperative PSA DT of at least 12 months or no PSA failure. Most men with these preoperative characteristics and a postoperative PSA DT of 12 months or more had a persistent postoperative PSA level of at least 0.2 ng/mL that did not exceed 0.25 ng/mL after a median follow-up of 3.6 years. CONCLUSION A postoperative PSA DT less than 3 months is associated with a preoperative PSA velocity more than 2.0 ng/mL/yr and high-grade disease. Select men with a postoperative PSA DT more than 12 months may not require salvage radiation therapy.

Congenital uterine anomalies and adverse pregnancy outcomes

OBJECTIVE We sought to estimate whether the presence of a maternal uterine anomaly is associated with adverse pregnancy outcomes. STUDY DESIGN This retrospective cohort study included singleton pregnancies undergoing routine anatomic survey from 1990 through 2008 at a major tertiary care medical center. Pregnancies with a diagnosis of uterine anomaly (uterine septum, unicornuate uterus, bicornuate uterus, uterine didelphys) were compared to those with normal anatomy. Primary outcomes of interest were spontaneous preterm birth (PTB), breech presentation, and cesarean delivery. RESULTS The presence of an anomaly was associated with PTB <34 weeks (adjusted odds ratio [aOR], 7.4; 95% confidence interval [CI], 4.8-11.4; P < .01), PTB <37 weeks (aOR, 5.9, 95% CI, 4.3-8.1; P < .01), primary nonbreech cesarean delivery (aOR, 2.6; 95% CI, 1.7-4.0; P < .01), preterm premature rupture of membranes (aOR, 3.2; 95% CI, 1.8-5.6; P < .01), and breech presentation (aOR, 8.6; 95% CI, 6.2-12.0; P < .01). CONCLUSION Women with a uterine anomaly are at risk for PTB, highlighting an at-risk population that needs additional study for possible interventions for PTB prevention.

Screening for Prostate Cancer in High Risk Populations

PURPOSE Black men and men with a family history of prostate cancer are at higher risk for this disease and may have an earlier age of onset. Consequently, screening at a younger age has been recommended for high risk men, however, there are limited data on actual screening results in young, high risk populations. MATERIALS AND METHODS In men 50 years old or older we compared screening results in 1,224 black men, 1,227 men with a positive family history and 63 men who were both with those of 15,964 nonblack men with no known family history. In high risk men in their forties we also evaluated the percent with abnormal screening tests, the positive predictive value of screening tests, cancer detection rates and the prognostic features of tumors detected. RESULTS In men 50 years old or older prostate cancer detection rates were 6.4% for controls compared with 10.3%, 10.5% and 17.5%, respectively, for the high risk groups. Among high risk men screened in their forties 8% had suspicious screening tests and approximately 55% who underwent a biopsy had cancer detected. Of tumors detected 80% were organ confined and all but 1 were of moderate Gleason grade 5 years old or older. Only 1 tumor (7%) fulfilled the published criteria for a possibly harmless cancer. CONCLUSIONS Black men and men with a family history of prostate cancer are at a 75% to 80% higher risk for prostate cancer. On initial screening of high risk men in their fourth decade only 8% have positive screening tests; however, approximately 55% of these men have tumors, most of which are medically important with favorable prognostic features.

Evidence to support a continued stage migration and decrease in prostate cancer specific mortality

PURPOSE We evaluated whether the proportion of patients with a postoperative PSA-DT less than 3 months, a surrogate for PCSM, decreased significantly during the PSA era. MATERIALS AND METHODS Between July 1988 and July 2002, 3,719 men with clinically localized prostate cancer treated with RP comprised the study cohort. A chi-square metric was used to compare the preoperative and postoperative characteristics, 5-year actual PSA failure rates, and PSA-DTs for patients treated during the 2 equally divided eras of the early PSA era, July 1988 to July 1995 and the late PSA era, August 1995 to July 2002. RESULTS Patients presenting in the more recent PSA era were of younger age (p < 0.0001), with earlier stage (p < 0.0001) and lower grade disease (p = 0.01). Similarly, patients had lower grade (p < 0.001), stage (p < 0.0001), and positive margin (p < 0.0001) and lymph node rates (p = 0.0002) at RP. The 5-year actual PSA failure rates decreased from 14.3% in the early PSA era to 2.5% in the later PSA era (p < 0.0001). There was a 37% reduction in the proportion of patients with a PSA-DT less than 3 months, corresponding to a decrease in absolute magnitude from 9% to 5.7% between the 2 eras. Absolute reductions of 3.1% and 9% were also noted for the proportion of PSA-DTs of 3 to 5.99 months and 6 to 11.99 months, respectively, whereas PSA-DTs of 12 months or greater increased by 15.3%. CONCLUSIONS During the recent PSA era, postoperative PSA failure has significantly decreased and PSA-DTs have increased, suggesting that PCSM will continue to decrease.

Robustness of free prostate specific antigen measurements to reduce unnecessary biopsies in the 2.6 to 4.0 ng./ml. range

PURPOSE Prostate specific antigen (PSA) cutoffs lower than 4.0 ng./ml. are being evaluated more frequently but lower PSA cutoffs increase the number of prostatic biopsies. PSA exists in several forms free and complexed to proteins. Percent free PSA is lower in men with prostate cancer. Accordingly, free PSA and complexed PSA have been used to distinguish between cancer and benign disease in the diagnostic gray zone of 4 to 10 ng./ml. to eliminate unnecessary biopsies. There are limited data on the robustness of free PSA measurements in the 2.6 to 4.0 ng./ml. total PSA range. MATERIALS AND METHODS We evaluated percent free PSA measurements to discriminate between cancer and benign conditions in 965 consecutive volunteers in a prostate cancer screening study who underwent prostatic biopsy for a PSA of 2.6 to 4.0 ng./ml. and had benign digital rectal examination. RESULTS Overall 25% of men had cancer detected. A 25% free PSA cutoff detected 85% of cancers and avoided 19% of negative (cancer-free) biopsies, while a 30% free PSA cutoff detected 93% of cancers and avoided only 9% of negative biopsies. Of those men who underwent radical prostatectomy 132 (80%) had pathologically organ confined tumors. Only 5% of these tumors fulfilled the published pathological criteria for possibly clinically unimportant tumors. CONCLUSIONS Percent free PSA provides risk assessment but does not eliminate many unnecessary prostatic biopsies while maintaining a high sensitivity in the narrow total PSA range of 2.6 to 4.0 ng./ml.

Pathological characteristics of prostate cancer detected through prostate specific antigen based screening.

PURPOSE Since the introduction of PSA testing for CaP, there has been an increase in CaP detection. However, it is uncertain to what extent clinically insignificant tumors are being diagnosed and treated. In a large, community based population we determined the pathological characteristics of screening detected cancers. MATERIALS AND METHODS From 1989 to 2001, 35,661 men were enrolled in a longitudinal prostate cancer screening study. Data were available on 3,492 of the 3,568 men (98%) diagnosed with CaP during this study period. Radical prostatectomy was performed in 2,254 men (63%). Clinical stage, Gleason score and pathological analysis were recorded and analyzed in the context of preoperative PSA, digital rectal examination findings, PSA velocity and the year of cancer detection. RESULTS CaP was detected in 10% of men. Virtually all cases were clinically localized (99.8%) and approximately 70% treated with radical prostatectomy were pathologically organ confined disease. Fewer than 10% of tumors would be considered clinically insignificant based on 2 previously published pathological criteria. CONCLUSIONS Compared to the high prevalence of CaP found in autopsy studies there is a lower detection rate using current screening protocols. Although the outcomes are unknown if these tumors had been left untreated, the majority met pathological criteria for significant cancer.

The effects of obesity on the first stage of labor.

OBJECTIVE: To estimate the effects of obesity on the duration and progression of the first stage of labor in a predominantly obese population and estimate the dose–effect with increasing classes of obesity. METHODS: We performed a retrospective cohort study of labor progression among 5,204 consecutive parturients with singleton term pregnancies (37 weeks of gestation or more) and vertex presentation who completed the first stage of labor. Two comparison groups were defined by body mass index (BMI) less than 30 (n=2,413) or 30 or more (n=2,791). Repeated-measures analysis with polynomial modeling was used to construct labor curves. The duration and progression among women with BMIs less than 30 and BMIs of 30 or more were compared in a multivariable interval-censored regression model adjusting for parity, type of labor onset, race, and birth weight more than 4,000 g. RESULTS: The labor curves indicate longer duration and slower progression of the first stage of labor among women with BMIs of 30 or more for both nulliparous and multiparous women. Multivariable interval-censored regression analysis confirmed significantly longer duration (4–10 cm: 4.7 compared with 4.1 hours, P<.01) and slower progression of cervical dilation from 4 to 6 cm (2.2 compared with 1.9 hours, P<.01 with a range of 0.5–10.0 hours) among women with BMIs of 30 or more after adjusting for confounders. CONCLUSION: The overall duration is longer and progression of the early part of the first stage of labor is slower in obese women. This suggests that obesity should be considered in defining norms for management of labor, particularly in the early part of the first stage. LEVEL OF EVIDENCE: II

Association and prediction of neonatal acidemia.

OBJECTIVE The objective of this study was to estimate the predictive ability of electronic fetal monitoring (EFM) patterns immediately prior to delivery for acidemia at term birth. STUDY DESIGN This was a 4-year retrospective cohort study of 5388 consecutive singleton, nonanomalous gestations of 37 weeks or longer. The primary exposure was the EFM pattern in the 30 minutes preceding delivery. EFM patterns were prospectively interpreted using Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) nomenclature as well as non-NICHD measurements of decelerations. The primary outcome was umbilical cord arterial pH of 7.10 or less. RESULTS Four NICHD-defined EFM features within the 30 minutes prior to birth demonstrated the greatest association with acidemia: repetitive prolonged decelerations (area under the curve [AUC] 0.81), baseline tachycardia (AUC 0.80), repetitive variable decelerations (AUC 0.79), and repetitive late decelerations (0.78) after adjusting for nulliparity, fever, prolonged first stage, and obesity. A non-NICHD measure, total deceleration area, demonstrated superior predictive ability for acidemia (AUC 0.83, P = .04). CONCLUSION A non-NICHD measure of deceleration frequency and severity in the second stage performed superior to 4 NICHD EFM features for predicting fetal acidemia.