Allison F. Vitonis

Conditions Associated with Antibodies Against the Tumor-Associated Antigen MUC1 and Their Relationship to Risk for Ovarian Cancer

Many cancers, including ovarian, overexpress epithelial mucin (MUC1) and promote anti-MUC1 antibodies that may correlate with more favorable prognosis. By extension, risk for ovarian cancer might be reduced by preexisting MUC1-specific immunity. We measured anti-MUC1 antibodies in 705 control women, identified events predicting antibodies, and estimated ovarian cancer risk by comparing profiles of events generating antibodies in controls with those in 668 ovarian cancer cases. Factors predicting antibodies included oral contraceptive use, breast mastitis, bone fracture or osteoporosis, pelvic surgeries, nonuse of talc in genital hygiene, and to a lesser extent intrauterine device use and current smoking. There was a significant increase in the likelihood of having anti-MUC1 antibodies from 24.2% in women with 0 or 1 condition, to 51.4% in those with five or more conditions. By the same index of events, the risk for ovarian cancer was inversely associated with number of conditions predisposing to anti-MUC1 antibodies. Compared with having experienced 0 or 1 event, the adjusted risk for ovarian cancer decreased progressively with relative risks (and 95% confidence limits) of 0.69 (0.52-0.92), 0.64 (0.47-0.88), 0.49 (0.34-0.72), and 0.31 (0.16-0.61), respectively for women with two, three, four, and five or more events related to the presence of antibodies (Ptrend < 0.0001.) We conclude that several traditional and new risk factors for ovarian cancer may be explained by their ability to induce MUC1 immunity through exposure of MUC1 to immune recognition in the context of inflammatory or hormonal processes in various MUC1-positive tissues.

Flavonoid intake and ovarian cancer risk in a population-based case-control study

Several recent studies have evaluated the association between dietary flavonoid intake and ovarian cancer risk, and all reported significant or suggestive inverse associations with certain flavonoids or flavonoid subclasses; however, most of these studies were small to moderate in size. We, therefore, examined this association in a large, population‐based case‐control study. We calculated intake of 5 common dietary flavonoids (myricetin, kaempferol, quercetin, luteolin, and apigenin), as well as total intake of these flavonoids, for 1,141 cases and 1,183 frequency‐matched controls. We used unconditional logistic regression to estimate the relative risk (RR) of ovarian cancer for each quintile of flavonoid intake when compared with the lowest quintile. We did not observe an association between total flavonoid intake and ovarian cancer risk. The multivariable‐adjusted RR for the highest versus lowest quintile of total flavonoid intake was 1.06 (95% confidence interval [CI] = 0.78–1.45). In analyses of each individual flavonoid, only intake of apigenin was associated with a borderline significant decrease in risk (RR, highest vs. lowest quintile = 0.79, 95% CI = 0.59–1.06; p‐trend = 0.26), and this association was significant after adjustment for intake of the other 4 individual flavonoids (comparable RR = 0.72, 95% CI = 0.53–0.98; p‐trend = 0.09). These results provide limited support for an association between flavonoid intake and ovarian cancer risk. However, given the findings of previous studies and the biologic plausibility of this association, additional studies are warranted.

Serum Prolactin and TSH in an In Vitro Fertilization Population: Is There a Link Between Fertilization and Thyroid Function?

AbstractPurpose: Measurements of TSH and prolactin are generally included in the evaluation of female infertility, but their value in women coming to in vitro fertilization (IVF) has been questioned. Methods: In this study, we sought to investigate whether prolactin or TSH, measured in 509 specimens collected prior to therapy, predicted outcome in a prospective study of couples undergoing IVF between 1994 and 2001. Results: TSH was higher in women whose fertility problem was attributed to a male factor, and prolactin was lower if the measurement was taken during menses. TSH and prolactin were positively correlated (p < 0.0001). Neither TSH nor prolactin levels correlated with overall IVF outcome; however, TSH levels were significantly higher among women who produced oocytes that failed to be fertilized and this finding persisted after adjustment for several covariates, including sperm motility. Among women who had a least one oocyte inseminated, the likelihood that they would have fewer than 50% of their eggs fertilized was significantly related to higher TSH levels in a multivariate model. Conclusion: We conclude that TSH may predict poor fertilization in IVF and reflect the importance of thyroid hormones in oocyte physiology.

Open Power Morcellation Versus Contained Power Morcellation Within an Insufflated Isolation Bag: Comparison of Perioperative Outcomes

STUDY OBJECTIVE To compare perioperative outcomes, particularly operative time, between uncontained and in-bag power morcellation of uterine tissue at the time of laparoscopic surgery. DESIGN Canadian Task Force classification II-3. SETTING Academic tertiary care hospitals. PATIENTS Women undergoing laparoscopic hysterectomy or myomectomy who required morcellation of uterine tissue for specimen extraction. INTERVENTIONS Outcomes among patients who had in-bag power morcellation were compared with outcomes among patients who had traditional power morcellation. The technique for in-bag morcellation entails placing the specimen into a large containment bag within the abdomen, insufflating the bag within the peritoneal cavity, and then using a power morcellator to remove the specimen from inside the bag. MEASUREMENTS AND MAIN RESULTS The cohort consisted of 85 consecutive patients who underwent surgery with morcellation of uterine tissue. Prospective data collected from 36 patients who underwent in-bag morcellation were compared with retrospective data collected from the immediately preceding 49 patients who had uncontained power morcellation. Baseline demographics were comparable between the 2 groups although women who underwent in-bag morcellation were on average older than the open morcellation group (mean age in years [standard deviation], 49.19 [1.12] vs 44.06 [8.93]; p = .01). The mean operating room time was longer in the in-bag morcellation group (mean time in minutes [standard deviation], 119.0 [55.91] vs 93.13 [44.90]; p = .02). The estimated blood loss, specimen weight, hospital length of stay, and perioperative complication rate did not vary between the 2 groups. Operative times did not vary significantly by surgeon. There were no cases of malignancy or isolation bag disruption. CONCLUSIONS In-bag power morcellation, a tissue extraction technique developed to reduce the risk of tissue dissemination, results in perioperative outcomes comparable with the traditional laparoscopic approach. In this cohort, the mean operative time was prolonged by 26 minutes with in-bag morcellation but may potentially be reduced with further refinement of the technique.

World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: III. Fluid biospecimen collection, processing, and storage in endometriosis research

Objective To harmonize standard operating procedures (SOPs) and standardize the recording of associated data for collection, processing, and storage of human tissues relevant to endometriosis. Design An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries on five continents. Setting In 2013, two workshops were conducted followed by global consultation, bringing together 54 leaders in endometriosis research and sample processing from around the world. Patient(s) None. Intervention(s) Consensus SOPs were based on: 1) systematic comparison of SOPs from 24 global centers collecting tissue samples from women with and without endometriosis on a medium or large scale (publication on >100 cases); 2) literature evidence where available, or consultation with laboratory experts otherwise; and 3) several global consultation rounds. Main Outcome Measure(s) Standard recommended and minimum required SOPs for tissue collection, processing, and storage in endometriosis research. Result(s) We developed “recommended standard” and “minimum required” SOPs for the collection, processing, and storage of ectopic and eutopic endometrium, peritoneum, and myometrium, and a biospecimen data collection form necessary for interpretation of sample-derived results. Conclusion(s) The EPHect SOPs allow endometriosis research centers to decrease variability in tissue-based results, facilitating between-center comparisons and collaborations. The procedures are also relevant to research into other gynecologic conditions involving endometrium, myometrium, and peritoneum. The consensus SOPs are based on the best available evidence; areas with limited evidence are identified as requiring further pilot studies. The SOPs will be reviewed based on investigator feedback and through systematic triannual follow-up. Updated versions will be made available at: http://endometriosisfoundation.org/ephect.

Prognostic significance and predictors of the neutrophil-to-lymphocyte ratio in ovarian cancer

OBJECTIVE To investigate the neutrophil-to-lymphocyte ratio (NLR) from peripheral blood, a general measure of inflammation, in ovarian cancer. METHODS White cell counts and CA125 levels before treatment, tumor features, and questionnaire data on 519 women with ovarian cancer at two Boston hospitals were recorded. Counts were log-transformed and effects on these by tumor features and epidemiologic variables assessed by analysis of variance and generalized linear models. Cox proportional hazards models were used to assess effects on overall survival. RESULTS Greater NLR was associated with higher tumor stage and grade, presence of ascites, and bilateral disease and correlated with risk factors including Jewish ethnicity, taller height, more ovulatory cycles, and family history of cancer in premenopausal women and talc use in all women. CA125 was positively correlated with neutrophil count, monocyte count, and NLR and inversely correlated with lymphocyte count. In a multivariate adjusted analysis, high NLR predicted poorer survival and high lymphocyte count better survival. CONCLUSION An elevated NLR before treatment signals more aggressive disease and correlates with risk factors for ovarian cancer. CA125 directly correlates with neutrophils which may reflect secretion of both CA125 and neutrophilic growth factors by the tumor. CA125 inversely correlates with lymphocytes which may reflect the ability of some neutrophilic factors to induce lymphopenia and/or binding of CA125 to lymphocytes removing CA125 from the serum pool. Links between NLR, CA125, and epidemiologic factors may provide new clues about the pathogenesis and progression of ovarian cancer.

Assessing Ovarian Cancer Risk When Considering Elective Oophorectomy at the Time of Hysterectomy

OBJECTIVE: To develop a risk-factor score that may provide additional guidance to women and their physicians regarding elective bilateral salpingo-oophorectomy at the time of hysterectomy. METHODS: From a case–control study conducted from 1992 to 2008 in women residing in eastern Massachusetts or New Hampshire, we selected 1,098 women with invasive ovarian cancer (case group) and 1,363 for the control group who were older than 40 years and had neither hysterectomy nor a personal or family history of breast or ovarian cancer. Using logistic regression, we identified key risk factors and built a risk score. The score was separately assessed in 126 women in the case group and 156 in the control group with excluded prior hysterectomy to determine whether women who developed ovarian cancer could have been distinguished. RESULTS: Summing eight conditions found to be associated with ovarian cancer (Jewish ethnicity, less than 1 year of oral contraceptive use, nulliparity, no breastfeeding, no tubal ligation, painful periods or endometriosis, polycystic ovary syndrome or obesity, talc use), we created a five-level score. Assigning average risk to those with a score of 2, the odds ratios varied from 0.56 (95% confidence interval [CI] 0.42–0.74) for a score of 0–1 to 3.30 (95% CI 2.50–4.35) for a score of 5 or greater (P trend <.001). The risk score was higher for women who developed ovarian cancer after hysterectomy than those who did not (P=.01). Lifetime risks for ovarian cancer for a woman at age 40 years are changed from 1.2% with a 0–1 score to 6.6% with a score of 5 or higher. CONCLUSION: We developed a risk-assessment tool that can quantify womens risk for ovarian cancer and should be validated in other data sets. LEVEL OF EVIDENCE: II

Characteristics of patients with endometriosis in the United States and the United Kingdom

OBJECTIVE To investigate differences in characteristics of patients with endometriosis in the United States and the United Kingdom. DESIGN Patient questionnaire. SETTING Two university-based endometriosis referral centers. PATIENT(S) Women with surgically diagnosed endometriosis. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Patient demographics, menstrual and obstetric history, contraceptive use, medical history, risk factors, family history, endometriosis diagnosis, and current pain status and treatment. RESULT(S) Most demographic characteristics were similar between groups. However, patients in the United States were diagnosed at a younger age than were patients in the United Kingdom (25.6 +/- 6.7 years vs. 28.0 +/- 7.1 years) and more commonly presented with an ovarian mass. More U.K. women used oral contraceptives before diagnosis and were younger at first use. U.K. patients underwent fewer additional surgeries than U.S. patients but reported that surgery alone provided the best relief of symptoms, whereas most U.S. patients reported that surgical and medical therapy together provided the best relief of symptoms. CONCLUSION(S) The many similarities in demographics and symptoms among women with endometriosis in the U.S. and the U.K. support the universality of the disease process. Despite a variety of treatments, most patients from both groups still experienced pain from their endometriosis at the time of the survey.

Views and reviewsWorld Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: III. Fluid biospecimen collection, processing, and storage in endometriosis research

Objective To harmonize standard operating procedures (SOPs) and standardize the recording of associated data for collection, processing, and storage of fluid biospecimens relevant to endometriosis. Design An international collaboration involving 34 clinical/academic centers and 3 industry collaborators from 16 countries on 5 continents. Setting In 2013, 2 workshops were conducted, followed by global consultation, bringing together 54 leaders in endometriosis research and sample processing worldwide. Patient(s) None. Intervention(s) Consensus SOPs were based on: [1] systematic comparison of SOPs from 18 global centers collecting fluid samples from women with and without endometriosis on a medium/large scale (publication on >100 cases), [2] literature evidence where available, or consultation with laboratory experts otherwise, and [3] several global consultation rounds. Main Outcome Measure(s) Standard recommended and minimum required SOPs for biofluid collection, processing, and storage in endometriosis research. Result(s) We developed recommended standard and minimum required SOPs for the collection, processing, and storage of plasma, serum, saliva, urine, endometrial/peritoneal fluid, and menstrual effluent, and a biospecimen data-collection form necessary for interpretation of sample-derived results. Conclusion(s) The Endometriosis Phenome and Biobanking Harmonisation Project SOPs allow endometriosis research centers to decrease variability in biofluid sample results, facilitating between-center comparisons and collaborations. The procedures are also relevant to research into other female conditions involving biofluid samples subject to cyclic reproductive influences. The consensus SOPs are based on the best available evidence; areas with limited evidence are identified as requiring further pilot studies. The SOPs will be reviewed based on investigator feedback, and through systematic tri-annual follow-up. Updated versions will be made available at: endometriosisfoundation.org/ephect.

World Endometriosis Research Foundation Endometriosis Phenome and biobanking harmonization project: II. Clinical and covariate phenotype data collection in endometriosis research

Objective To harmonize the collection of nonsurgical clinical and epidemiologic data relevant to endometriosis research, allowing large-scale collaboration. Design An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries on five continents. Setting In 2013, two workshops followed by global consultation, bringing together 54 leaders in endometriosis research. Patients None. Intervention(s) Development of a self-administered endometriosis patient questionnaire (EPQ), based on [1] systematic comparison of questionnaires from eight centers that collect data from endometriosis cases (and controls/comparison women) on a medium to large scale (publication on >100 cases); [2] literature evidence; and [3] several global consultation rounds. Main Outcome Measure(s) Standard recommended and minimum required questionnaires to capture detailed clinical and covariate data. Result(s) The standard recommended (EPHect EPQ-S) and minimum required (EPHect EPQ-M) questionnaires contain questions on pelvic pain, subfertility and menstrual/reproductive history, hormone/medication use, medical history, and personal information. Conclusion(s) The EPQ captures the basic set of patient characteristics and exposures considered by the WERF EPHect Working Group to be most critical for the advancement of endometriosis research, but is also relevant to other female conditions with similar risk factors and/or symptomatology. The instruments will be reviewed based on feedback from investigators, and–after a first review after 1 year–triannually through systematic follow-up surveys. Updated versions will be made available through http://endometriosisfoundation.org/ephect.