Abstract Objective The recurrence rate of anti‐SSA/Ro–associated congenital heart block (CHB) is 17%. Sustained reversal of third‐degree block has never been achieved. Based on potential reduction of maternal autoantibody titers as well as fetal inflammatory responses, intravenous immunoglobulin (IVIG) was evaluated as preventive therapy for CHB. Methods A multicenter, prospective, open‐label study based on Simon's 2‐stage optimal design was initiated. Enrollment criteria included the presence of anti‐SSA/Ro antibodies in the mother, birth of a previous child with CHB/neonatal lupus rash, current treatment with ≤20 mg/day of prednisone, and <12 weeks pregnant. IVIG (400 mg/kg) was given every 3 weeks from week 12 to week 24 of gestation. The primary outcome was the development of second‐degree or third‐degree CHB. Results Twenty mothers completed the IVIG protocol before the predetermined stopping rule of 3 cases of advanced CHB in the study was reached. CHB was detected at 19, 20, and 25 weeks; none of the cases occurred following the finding of an abnormal PR interval on fetal Doppler monitoring. One of these mothers had 2 previous children with CHB. One child without CHB developed a transient rash consistent with neonatal lupus. Sixteen children had no manifestations of neonatal lupus at birth. No significant changes in maternal titers of antibody to SSA/Ro, SSB/La, or Ro 52 kd were detected over the course of therapy or at delivery. There were no safety issues. Conclusion This study establishes the safety of IVIG and the feasibility of recruiting pregnant women who have previously had a child with CHB. However, IVIG at low doses consistent with replacement does not prevent the recurrence of CHB or reduce maternal antibody titers.
Sporadic cases of fallopian tube prolapse and various methods of management have been reported since the initial case described in 1902. Two cases were managed recently by a combined vaginal and laparoscopic approach. Total salpingectomy was accomplished with minimal difficulty and limited invasiveness. A brief summary of each case and detailed description of the operative technique are presented.
Abstract Introduction Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B) , rs10995190 ( ZNF365) , rs704010 ( ZMIZ1 ), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). Methods To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. Results Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P -trend = 3 × 10 -4 ). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P -trend = 3.1 × 10 -5 , P -difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P -trend = 0.015; rs1011970, P -trend = 0.048; rs865686, 2df- P = 0.007; rs1292011 2df- P = 0.03. rs10771399 ( PTHLH ) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P -trend = 4 × 10 -5 ) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P -trend = 0.049). Conclusions The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers.
5592 Background: We sought to evaluate the short-term response rate, toxicity and potential molecular changes following treatment with metformin for simple (SEH) and complex endometrial hyperplasia without atypia (CEH). Methods: Women with newly diagnosedsimple or complex endometrial hyperplasia without atypia by endometrial biopsy or dilation & curettage were enrolled onto a prospective multi-institutional single arm clinical trial, and treated with metformin for 3 months (850 mg daily x 4 weeks, then twice daily for 8 weeks), followed by repeat biopsy. Pathologic response and toxicity (CTCAE 4.1) were assessed. Expression of the estrogen (ER) and progesterone (PR) receptor and the metformin transporters (OCT1, OCT3, PMAT, MATE1, MATE2) were evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded endometrial specimens pre- and post-treatment. Slides were scanned using the Aperio ScanScope, and digital images were analyzed using Aperio ImageScope software. We report proportions as %, along with their exact 95% confidence intervals. Pre- and post- comparisons were done using the Wilcoxon signed-rank test. Reported p-values were nominal, or unadjusted for multiple testing. Results: 18 patients enrolled, with 16 evaluable, of whom all completed treatment. 56% (9/16, 95% CI 30%, 80%) showed pathologic response (6/9 SEH, 2/5 CEH, 1/2 SEH/CEH). Common toxicities included diarrhea (67%), nausea (39%), flatulence (28%); all were grade 1 except for grade 2 diarrhea (n = 2), GERD (n = 1), and nausea (n = 1). Before metformin, the median % positive staining cells was 98.9% for ER, 89.9% for PR, 50.8% for MATE2, 98.4% for MATE1, 26.5% for PMAT, 87.5% for OCT1 and 68.6% for OCT3. Expression of MATE2 (50.8 to 60.4% positive cells; 86.1 to 120.6 H-score, p = 0.048) and OCT3 (68.6 to 91.7% positive cells; 116.8 to 136.5 H-score, p = 0.017, 0.057 respectively) increased after metformin treatment, whereas expression of MATE1, PMAT, OCT1, ER, PR did not change. Conclusions: Approximately half of the patients with endometrial hyperplasia without atypia responded to short-term metformin treatment. Preliminary exploratory comparisons seem to indicate that MATE2 and OCT3 expression (by % positive cells and H-score) increases with metformin treatment. Clinical trial information: NCT01685762.
Two hundred and fifty-two women scheduled to undergo laparoscopy were randomly assigned to a Verres needle or direct insertion group. The groups were similar with respect to incidence of obesity, prior surgical treatment, indication for operation and level of training of the surgeon performing the procedure. There were no major complications associated with either technique. Minor complications (preperitoneal insufflation, failed entry or more than three attempts necessary to enter the peritoneal cavity with the trocar) were significantly more frequent (p < 0.05) in the Verres needle technique group. One hundred and thirteen of these patients underwent sterilization procedures. The mean times for performance of the laparoscopic procedure using the direct insertion and Verres needle techniques was 15.3 and 19.6 minutes, respectively. The time saved using the direct insertion technique is explained by a significant (p < 0.01) reduction in the mean laparoscope insertion time, which was 2.2 minutes and 5.9 minutes for the direct insertion and Verres needle techniques, respectively. We prefer the direct insertion technique for trocar placement because it has fewer minor complications and requires less operating time.
Abstract In vitro data and pilot clinical trial data suggest that green tea catechins may possess chemopreventive activity for cervical cancer and its precursor lesions. We conducted a randomized, double-blind, placebo controlled trial of Polyphenon E (decaffeinated and enriched green tea catechin extract) in women with persistent human papillomavirus (HPV) infection and low grade cervical intraepithelial neoplasia (CIN1) to evaluate the potentials of Polyphenon E for cervical cancer prevention. Ninety-eight eligible women were randomized to receive either Polyphenon E (containing 800 mg epigallocatechin gallate) or placebo once daily for 4 months. The primary study outcome was oncogenic HPV clearance and clearance of CIN1. Polyphenon E was shown to be acceptable, safe and well tolerated. There was no difference in the response rate by treatment allocation. Complete response, defined as negative for high risk HPV and normal histopathology, was noted in 7 (17.1%) and 6 (14.6%) women in the Polyphenon E and placebo arms, respectively. Partial response, defined as clearance of oncogenic HPV with evidence of CIN1, occurred more frequently in the placebo group 6 (14.6%) vs. 1 (2.4%) in the Polyphenon E arm. Progression, defined as persistent oncogenic HPV with histopathologic evidence of progression, was more common in the Polyphenon E group [3 (7.7%) vs. 6 (14.6%) in the placebo arm, although neither of these observations were statistically significant. Based on the largest randomized placebo-controlled trial of a green tea extract for HPV related cervical disease, we conclude that four months of Polyphenon E intervention did not promote the clearance of persistent high risk HPV and related CIN 1. Further studies may be necessary to better delineate the risk factors for persistent HPV infection and biology of the disease to facilitate the evaluation of chemopreventive strategies. Citation Format: Tomas Nuno, Francisco A.R. Garcia, Terri Cornelison, Amy L. Mitchell, David L. Greenspan, John W. Byron, Chiu-Hsieh Hsu, David S. Alberts, Sherry Chow. Results of a phase II randomized, double-blind, placebo controlled trial of Polyphenon E in women with persistent high-risk HPV infection and low-grade cervical intraepithelial neoplasia. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C50.
It is estimated that one-third of women will experience abnormal menstrual bleeding. The majority of these cases are not due to cancer or pregnancy complications and, as a result, women are faced with a variety of treatment alternatives, the selection of which is largely dependent on personal preferences for care rather than clinical outcomes. This randomized trial was designed to evaluate a preference elicitation tool to promote physician–patient collaborative decision making for treatment of abnormal uterine bleeding (AUB). Adaptive conjoint analysis (ACA) was used to create a preference elicitation tool in English and in Spanish. Women with AUB were enrolled to the study and randomly assigned to ACA or usual counseling at the initial clinic visit at four clinics (three in Indianapolis, IN, USA, and one in Southern Pines, NC, USA). The ACA tool elicited preferences across eight attributes: treatment efficacy; sexual function; medical care; cost; fertility; frequency of medication use; permanence; and recovery time. t tests were used to compare differences in the primary outcomes of decision regret and treatment satisfaction at the follow-up visit. The study was designed to have 80 % power to detect significant differences between groups for the primary outcomes of regret and satisfaction. Women were enrolled in the study between September 2009 and March 2012. 183 participants were randomized to ACA and 191 to usual counseling. Overall, mean (standard deviation) treatment satisfaction was high at 35.71 (9.72) (scale of 0–44), and decision regret was low at 25.9 (21.0) (scale of 0–100), creating ceiling effects for the selected outcome variables; there were no significant differences between the ACA and control groups at the follow-up assessment. There was a strong inverse relationship between age and decision regret (p = 0.007). Exploratory subgroup analysis in the youngest quartile comprising 64 women aged 19–35 years showed a statistically non-significant difference in mean regret scores for the ACA group versus usual counseling (24.6 vs. 34.6, respectively; p = 0.08). A preference elicitation tool at the initial consultation visit did not reduce decision regret or improve treatment satisfaction among patients with AUB; however, there is a need for additional research to further understand this tool’s potential role in promoting collaborative decision making, which may be particularly important among younger women.
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