Occult Uterine Sarcoma and Leiomyosarcoma: Incidence of and Survival Associated With Morcellation.

OBJECTIVE: To estimate the incidence of occult uterine sarcoma and leiomyosarcoma in hysterectomies for leiomyomas and the risk associated with their morcellation. METHODS: We conducted a population-based cohort study. All uterine sarcomas from 2006-2013 in an integrated health care system were identified. Age- and race-specific incidences of occult uterine sarcoma were calculated. Kaplan-Meier survival analysis was performed. Crude and adjusted risk ratios of recurrence and death associated with morcellation at 1, 2, and 3 years were estimated using Poisson regression with inverse probability weighting. RESULTS: There were 125 hysterectomies with occult uterine sarcomas identified among 34,728 hysterectomies performed for leiomyomas. The incidence of occult uterine sarcoma and leiomyosarcoma was 1 of 278 or 3.60 (95% confidence interval [CI] 2.97-4.23) and 1 of 429 or 2.33 (95% CI 1.83-2.84) per 1,000 hysterectomies. For stage I leiomyosarcoma (n=111), eight (7.2%) were power and 27 (24.3%) nonpower-morcellated. The unadjusted 3-year probability of disease-free survival for no morcellation, power and nonpower morcellation was 0.54, 0.19, and 0.51, respectively (P=.15); overall survival was 0.64, 0.75, and 0.68, respectively (P=.97). None of the adjusted risk ratios for recurrence or death were significant except for death at 1 year for power and nonpower morcellation groups combined (6/33) compared with no morcellation (4/76) (5.12, 95% CI 1.33-19.76, P=.02). We had inadequate power to infer differences for all other comparisons including 3-year survival and power morcellation. CONCLUSION: Morcellation is associated with decreased early survival of women with occult leiomyosarcomas. We could not accurately assess associations between power morcellation and 3-year survival as a result of small numbers.

Maternal obesity, gestational weight gain, and offspring adiposity: the exploring perinatal outcomes among children study.

OBJECTIVE: To determine whether adequate vs excessive gestational weight gain (GWG) attenuated the association between maternal obesity and offspring outcomes. STUDY DESIGN: Data from 313 mother-child pairs participating in the Exploring Perinatal Outcomes among Children study were used to test this hypothesis. Maternal prepregnancy body mass index (BMI) and weight measures throughout pregnancy were abstracted from electronic medical records. GWG was categorized according to the 2009 Institute of Medicine criteria as adequate or excessive. Offspring outcomes were obtained at a research visit (average age 10.4 years) and included BMI, waist circumference (WC), subcutaneous adipose tissue (SAT) and visceral adipose tissue, high-density lipoprotein cholesterol, and triglyceride levels. RESULTS: More overweight/obese mothers exceeded the Institute of Medicine GWG recommendations (68%) compared with normal-weight women (50%) (P < .01). Maternal prepregnancy BMI was associated with worse childhood outcomes, particularly among offspring of mothers with excessive GWG (increased BMI [20.34 vs 17.80 kg/m(2)], WC [69.23 vs 62.83 cm], SAT [149.30 vs 90.47 cm(2)], visceral adipose tissue [24.11 vs 17.55 cm(2)], and homeostatic model assessment [52.52 vs 36.69], all P < .001). The effect of maternal prepregnancy BMI on several childhood outcomes was attenuated for offspring of mothers with adequate vs excessive GWG (P < .05 for the interaction between maternal BMI and GWG status on childhood BMI, WC, SAT, and high-density lipoprotein cholesterol). CONCLUSION: Our findings lend support for pregnancy interventions aiming at controlling GWG to prevent childhood obesity.

Feasibility of self-collection of fecal specimens by randomly sampled women for health-related studies of the gut microbiome.

BACKGROUND: The field of microbiome research is growing rapidly. We developed a method for self-collection of fecal specimens that can be used in population-based studies of the gut microbiome. We conducted a pilot study to test the feasibility of our methods among a random sample of healthy, postmenopausal women who are members of Kaiser Permanente Colorado (KPCO). We aimed to collect questionnaire data, fecal and urine specimens from 60 women, aged 55-69, who recently had a normal screening mammogram. We designed the study such that all questionnaire data and specimens could be collected at home. RESULTS: We mailed an invitation packet, consent form and opt-out postcard to 300 women, then recruited by telephone women who did not opt-out. Verbally consented women were mailed an enrollment package including a risk factor questionnaire, link to an online diet questionnaire, specimen collection kit, and instructions for collecting stool and urine. Specimens were shipped overnight to the biorepository. Of the 300 women mailed an invitation packet, 58 (19%) returned the opt-out postcard. Up to 3 attempts were made to telephone the remaining women, of whom 130 (43%) could not be contacted, 23 (8%) refused, and 12 (4%) were ineligible. Enrollment packages were mailed to 77 women, of whom 59 returned the risk factor questionnaire and specimens. We found no statistically significant differences between enrolled women and those who refused participation or could not be contacted. CONCLUSIONS: We demonstrated that a representative sample of women can be successfully recruited for a gut microbiome study; however, significant personal contact and carefully timed follow-up from the study personnel are required. The methods employed by our study could successfully be applied to analytic studies of a wide range of clinical conditions that have been postulated to be influenced by the gut microbial population.

The long-term impact of intrauterine growth restriction in a diverse U.S. cohort of children: the EPOCH study.

OBJECTIVE: To explore the long-term impact of intrauterine growth restriction (IUGR) among a diverse, contemporary cohort of U.S. children. DESIGN AND METHODS: A retrospective cohort of 42 children exposed to IUGR and 464 unexposed who were members of Kaiser Permanente of Colorado. Height and weight measurements since birth and measures of abdominal adiposity and insulin-resistance were measured at an average age of 10.6 (±1.3) years. RESULTS: Infants born IUGR experienced "catch-up growth" in the first 12 months of life at a rate of 3.58 kg/m² compared to 2.36 kg/m² in unexposed infants (P = 0.01). However, after 1 year of age, no differences in BMI growth velocity were observed. Nevertheless children exposed to IUGR had higher waist circumference (67.0 vs. 65.3 cm, P = 0.03), higher insulin (15.2 vs. 11.0 µU/ml, P = 0.0002), higher HOMA-IR (2.8 vs. 2.3, P = 0.03), and lower adiponectin levels (9.0 vs. 12.0 µg/ml, P = 0.003) in adolescence, independent of other childhood and maternal factors. CONCLUSIONS: Our data from a contemporary US cohort suggests that children exposed to IUGR have increased abdominal fat and increased insulin resistance biomarkers despite no differences in BMI growth patterns beyond 12 months of age. These data provide further support for the fetal programming hypothesis.

Improving quality of breast cancer surgery through development of a national breast cancer surgical outcomes (BRCASO) research database.

BACKGROUND: Common measures of surgical quality are 30-day morbidity and mortality, which poorly describe breast cancer surgical quality with extremely low morbidity and mortality rates. Several national quality programs have collected additional surgical quality measures; however, program participation is voluntary and results may not be generalizable to all surgeons. We developed the Breast Cancer Surgical Outcomes (BRCASO) database to capture meaningful breast cancer surgical quality measures among a non-voluntary sample, and study variation in these measures across providers, facilities, and health plans. This paper describes our study protocol, data collection methods, and summarizes the strengths and limitations of these data. METHODS: We included 4524 women ≥18 years diagnosed with breast cancer between 2003-2008. All women with initial breast cancer surgery performed by a surgeon employed at the University of Vermont or three Cancer Research Network (CRN) health plans were eligible for inclusion. From the CRN institutions, we collected electronic administrative data including tumor registry information, Current Procedure Terminology codes for breast cancer surgeries, surgeons, surgical facilities, and patient demographics. We supplemented electronic data with medical record abstraction to collect additional pathology and surgery detail. All data were manually abstracted at the University of Vermont. RESULTS: The CRN institutions pre-filled 30% (22 out of 72) of elements using electronic data. The remaining elements, including detailed pathology margin status and breast and lymph node surgeries, required chart abstraction. The mean age was 61 years (range 20-98 years); 70% of women were diagnosed with invasive ductal carcinoma, 20% with ductal carcinoma in situ, and 10% with invasive lobular carcinoma. CONCLUSIONS: The BRCASO database is one of the largest, multi-site research resources of meaningful breast cancer surgical quality data in the United States. Assembling data from electronic administrative databases and manual chart review balanced efficiency with high-quality, unbiased data collection. Using the BRCASO database, we will evaluate surgical quality measures including mastectomy rates, positive margin rates, and partial mastectomy re-excision rates among a diverse, non-voluntary population of patients, providers, and facilities.

Long-term impact of neonatal breastfeeding on childhood adiposity and fat distribution among children exposed to diabetes in utero.

OBJECTIVE: To evaluate whether breastfeeding attenuates increased childhood adiposity associated with exposure to diabetes in utero. RESEARCH DESIGN AND METHODS: Retrospective cohort study of 89 children exposed to diabetes in utero and 379 unexposed youth with measured BMI, waist circumference, skinfolds, visceral (VAT) and subcutaneous (SAT) abdominal fat. A measure of breast milk-months was derived from maternal self-report and used to categorize breastfeeding status as low (<6) and adequate (≥ 6 breast milk-months). Multiple linear regression was used to model the relationship between exposure to diabetes in utero and offspring adiposity outcomes among youth stratified according to breastfeeding status. RESULTS: Adequate (vs. low) breastfeeding status was associated with significantly lower BMI, waist circumference, SAT, and VAT at ages 6-13 years. Among youth in the low breastfeeding category, exposure to diabetes in utero was associated with a 1.7 kg/m(2) higher BMI (P = 0.03), 5.8 cm higher waist circumference (P = 0.008), 6.1 cm(2) higher VAT (P = 0.06), 44.6 cm(2) higher SAT (P = 0.03), and 0.11 higher ratio of subscapular-to-triceps skinfold ratio (P = 0.008). Among those with adequate breastfeeding in infancy, the effect of prenatal exposure to diabetes on childhood adiposity outcomes was not significant. CONCLUSIONS: Adequate breastfeeding protects against childhood adiposity and reduces the increased adiposity levels associated with exposure to diabetes in utero. These data provide support for mothers with diabetes during pregnancy to breastfeed their infants in order to reduce the risk of childhood obesity.

Diffusion of aromatase inhibitors for breast cancer therapy between 1996 and 2003 in the Cancer Research Network.

PURPOSE: Clinical trials demonstrated adjuvant aromatase inhibitor treatment is superior for decreasing breast cancer recurrence risk over adjuvant tamoxifen treatment as early as 2001. Yet clinical use for adjuvant treatment was not recommended by the American Society of Clinical Oncology until 2004. Aromatase inhibitor uptake after the first public presentation of randomized trial results but before the release of national guidelines is unclear. We evaluated diffusion of aromatase inhibitor dispensings for breast cancer treatment in integrated healthcare delivery systems across the United States. METHODS: We collected automated data for 13,245 women enrolled at seven integrated healthcare delivery systems in the Cancer Research Network. All women were aged >55 and diagnosed with estrogen receptor positive, invasive breast cancer between 1996 and 2003. We used electronic pharmacy data to identify aromatase inhibitor and tamoxifen dispensings through 2004. We evaluated the proportions of women who received hormone dispensings in two ways: (1) at any point after diagnosis to capture all use, and (2) in the two-year period following diagnosis to approximate adjuvant use. RESULTS: Over time, adjuvant aromatase inhibitor use increased whereas tamoxifen use decreased. Aromatase inhibitor dispensings within 2 years of diagnosis increased from 4.1% among women diagnosed in 2000 to 13% in 2001, 24% in 2002, and 40% in 2003. Tamoxifen use declined starting in 2001 at every system. CONCLUSION: Aromatase inhibitor use rose dramatically after 2001 while tamoxifen use decreased. It appears results from early clinical trials changed practice in these integrated healthcare systems before formal changes in national guidelines.

Do behavioral smoking reduction approaches reach more or different smokers? Two studies; similar answers.

There is a need for innovative approaches capable of reaching smokers who would not otherwise participate in efforts to modify their smoking. This paper reports on two studies to determine whether a smoking reduction intervention would appeal to additional or different types of smokers than do cessation interventions. Study 1 attempted to contact 160 HMO smokers scheduled for outpatient surgeries. In Study 2, actual pilot reduction and cessation programs were offered to 531 smokers about to undergo out-patient surgeries or procedures. In Study 1, 39% of those eligible elected smoking reduction; and 38% selected cessation. In Study 2 of those eligible, 22% began participation in the smoking reduction program; 12% preferred a cessation approach; and 65% declined. There were few demographic or smoking history differences among those who elected smoking reduction, cessation, or declined. Among this understudied population, a sizable proportion in both studies agreed to participate in smoking reduction. If replicated, this suggests that comprehensive programs that include a smoking reduction component could substantially increase their reach.

Cervical cancer in women with comprehensive health care access: attributable factors in the screening process.

BACKGROUND: Invasive cervical cancer is highly preventable, yet it continues to occur, even among women who have access to cancer screening and treatment services. To reduce cervical cancer among such women, reasons for its occurrence must be better understood. We examined factors associated with the diagnosis of cervical cancer among women enrolled in health plans. METHODS: We identified all cases of invasive cervical cancer (n = 833) diagnosed from January 1, 1995, through December 31, 2000, among women who were long-term members of seven prepaid comprehensive health plans and reviewed each woman's medical records for the 3 years prior to her cancer diagnosis. Women were classified into one of three categories based on Pap test histories 4-36 months before diagnosis: failure to screen with a Pap test, failure in detection by a Pap test, or failure in follow-up of an abnormal test result. RESULTS: The majority of cases (n = 464; 56%) were in women who had no Pap tests during the period 4-36 months prior to diagnosis. Of the remaining cases, 263 (32%) were attributed to Pap test detection failure and 106 (13%) to follow-up failure. Being older (odds ratio [OR] = 6.48, 95% confidence interval [CI] = 3.89 to 10.79) or living in an area of higher poverty (OR = 1.72, 95% CI = 1.11 to 2.67) or having a lower education level (OR= 1.52; 95% CI = 1.07 to 2.16) was associated with the likelihood of being assigned to the failure to screen category versus either of the other two categories. A total of 375 (81%) of the 464 patients who had not had Pap screening had had at least one outpatient visit 4-36 months prior to cancer diagnosis. The cancer diagnostic process was triggered by a routine screening examination in 44% of patients, whereas 53% of the patients presented with symptoms consistent with cervical cancer; the remaining 3% were identified fortuitously during the course of receiving noncervical care. CONCLUSIONS: To reduce the incidence of invasive cervical cancer among women with access to screening and treatment, Pap screening adherence should be increased. In addition, strategies to improve the accuracy of Pap screening could afford earlier detection of cervical cancer.

Increasing prevalence of gestational diabetes mellitus (GDM) over time and by birth cohort: Kaiser Permanente of Colorado GDM Screening Program.

OBJECTIVE: The prevalence of gestational diabetes mellitus (GDM) varies in direct proportion with the prevalence of type 2 diabetes in a given population or ethnic group. Given that the number of people with diabetes worldwide is expected to increase at record levels through 2030, we examined temporal trends in GDM among diverse ethnic groups. RESEARCH DESIGN AND METHODS: Kaiser Permanente of Colorado (KPCO) has used a standard protocol to universally screen for GDM since 1994. This report is based on 36,403 KPCO singleton pregnancies occurring between 1994 and 2002 and examines trends in GDM prevalence among women with diverse ethnic backgrounds. RESULTS: The prevalence of GDM among KPCO members doubled from 1994 to 2002 (2.1-4.1%, P < 0.001), with significant increases in all racial/ethnic groups. In logistic regression, year of diagnosis (odds ratio [OR] and 95% CI per 1 year = 1.12 [1.09-1.14]), mother's age (OR per 5 years = 1.7 [1.6-1.8]) and ethnicity other than non-Hispanic white (OR = 2.1 [1.9-2.4]) were all significantly associated with GDM. Birth year remained significant (OR = 1.06, P = 0.006), even after adjusting for prior GDM history. CONCLUSIONS: This study shows that the prevalence of GDM is increasing in a universally screened multiethnic population. The increasing GDM prevalence suggests that the vicious cycle of diabetes in pregnancy initially described among Pima Indians may also be occurring among other U.S. ethnic groups.

Reason for late-stage breast cancer: absence of screening or detection, or breakdown in follow-up?

BACKGROUND: Mammography screening increases the detection of early-stage breast cancers. Therefore, implementing screening should reduce the percentage of women who are diagnosed with late-stage disease. However, despite high national mammography screening rates, late-stage breast cancers still occur, possibly because of failures in screening implementation. METHODS: Using data from seven health care plans that included 1.5 million women aged 50 years or older, we conducted retrospective reviews of chart and automated data for 3 years before 1995-1999 diagnoses of late-stage (metastatic and/or tumor size > or =3 cm; case subjects, n = 1347) and early-stage breast cancers (control subjects, n = 1347). We categorized the earliest screening mammogram during the period 13-36 months before diagnosis as none (absence of screening), negative (absence of detection), or positive (potential breakdown in follow-up). We compared the proportion of case and control subjects in each category of screening implementation and estimated the likelihood (odds ratio [OR] with 95% confidence intervals [CIs]) of late-stage breast cancer. We also evaluated demographic characteristics associated with absence of screening in women with late-stage disease. All statistical tests were two-sided. RESULTS: Absence of screening, absence of detection, and potential breakdown in follow-up were distributed differently among case (52.1%, 39.5%, and 8.4%, respectively) and control subjects (34.4%, 56.9%, and 8.8%, respectively) (P = .03). Among all women, the odds of having late-stage cancer were higher among women with an absence of screening (OR = 2.17, 95% CI = 1.84 to 2.56; P<.001). Among case patients, women were more likely to be in the absence-of-screening group if they were aged 75 years or older (OR = 2.77, 95% CI = 2.10 to 3.65), unmarried (OR = 1.78, 95% CI = 1.41 to 2.24), or without a family history of breast cancer (OR = 1.84, 95% CI = 1.45 to 2.34). A higher proportion of women from census blocks with less education (58.5% versus 49.4%; P = .003) or lower median annual income (54.4% versus 42.9%; P = .004) were in the absence-of-screening category compared with the proportion for the other two categories combined. CONCLUSIONS: To reduce late-stage breast cancer occurrence, reaching unscreened women, including elderly, unmarried, low-income, and less educated women, should be made a top priority for screening implementation.