The impact of p16(ink4a) positivity in invasive vulvar cancer on disease-free and disease-specific survival, a retrospective study

Purpose To evaluate HPV and p16(ink4a) status as prognostic factors in patients with invasive vulvar cancer. Methods Retrospective analysis of disease-free (DFS) and disease-specific survival (DSS) of patients with invasive vulvar cancer at a single tertiary care center. Histology, HPV and p16(ink4a) status were evaluated in the context of a global multicenter trial. Logistic regression models were performed to identify the impact of p16(ink4a) positivity. Results 135 patients were included in the analysis. 32 (23.7%) showed a p16(ink4a) expression of over 25%. Disease-free and disease-specific survival was longer in p16(ink4a) positive patients (23 vs. 10 months, p = 0.004, respectively, 29 vs. 21 months, p = 0.016). In multivariate analysis, p16(ink4a) positivity was an independent parameter for DFS (p = 0.025, HR: 2.120 (1.100-4.085)), but not for DSS (p = 0.926, HR: 1.029 (0.558-1.901), in contrast to age and tumor stage. Conclusions Age and tumor stage negatively affect survival. However, disease-free survival is significantly longer in patients with p16(ink4a) positive invasive vulvar cancer

CXCL12 expression by healthy and malignant ovarian epithelial cells

<p>Abstract</p> <p>Background</p> <p>CXCL12 has been widely reported to play a biologically relevant role in tumor growth and spread. In epithelial ovarian cancer (EOC), CXCL12 enhances tumor angiogenesis and contributes to the immunosuppressive network. However, its prognostic significance remains unclear. We thus compared CXCL12 status in healthy and malignant ovaries, to assess its prognostic value.</p> <p>Methods</p> <p>Immunohistochemistry was used to analyze CXCL12 expression in the reproductive tracts, including the ovaries and fallopian tubes, of healthy women, in benign and borderline epithelial tumors, and in a series of 183 tumor specimens from patients with advanced primary EOC enrolled in a multicenter prospective clinical trial of paclitaxel/carboplatin/gemcitabine-based chemotherapy (GINECO study). Univariate COX model analysis was performed to assess the prognostic value of clinical and biological variables. Kaplan-Meier methods were used to generate progression-free and overall survival curves.</p> <p>Results</p> <p>Epithelial cells from the surface of the ovary and the fallopian tubes stained positive for CXCL12, whereas the follicles within the ovary did not. Epithelial cells in benign, borderline and malignant tumors also expressed CXCL12. In EOC specimens, CXCL12 immunoreactivity was observed mostly in epithelial tumor cells. The intensity of the signal obtained ranged from strong in 86 cases (47%) to absent in 18 cases (<10%). This uneven distribution of CXCL12 did not reflect the morphological heterogeneity of EOC. CXCL12 expression levels were not correlated with any of the clinical parameters currently used to determine EOC prognosis or with HER2 status. They also had no impact on progression-free or overall survival.</p> <p>Conclusion</p> <p>Our findings highlight the previously unappreciated constitutive expression of CXCL12 on healthy epithelia of the ovary surface and fallopian tubes, indicating that EOC may originate from either of these epithelia. We reveal that CXCL12 production by malignant epithelial cells precedes tumorigenesis and we confirm in a large cohort of patients with advanced EOC that CXCL12 expression level in EOC is not a valuable prognostic factor in itself.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00052468">NCT00052468</a></p

Decreased Ovarian Reserve Predicts Inexplicability of Recurrent Miscarriage? A Retrospective Analysis.

OBJECTIVE:To evaluate anti-Mullerian hormone, basal follicle stimulating hormone, luteinizing hormone, estradiol, and female age in women with recurrent miscarriage and to compare women with explained and idiopathic recurrent miscarriage. DESIGN:Retrospective cohort study. SETTING:University hospital, tertiary care center. PATIENTS:Women with recurrent miscarriage (78 explained, 66 idiopathic). INTERVENTION(S):None. MAIN OUTCOME MEASURES(S):Anti-Mullerian hormone, basal follicle stimulating hormone, luteinizing hormone, estradiol, and age. RESULTS:Anti-Mullerian hormone and estradiol were significantly lower in women with idiopathic recurrent miscarriage (median 1.2 ng/ml, IQR 0.6-2.1, and median 36.5 pg/ml, IQR 25.8-47.3, respectively) than in women with explained recurrent miscarriage (median 2.0 ng/ml, IQR 1.1-2.7, and median 42.5 pg/ml, IQR 32.8-59.8, respectively; p<0.05). Optimized cut-off values for the prediction of idiopathic recurrent miscarriage were <39.5 pg/ml for estradiol (sensitivity: 63.3%, 95% CI: 50.9-75.1; specificity: 56.4%, 95% CI: 44.7-67.6) and <1.90 ng/ml for anti-Mullerian hormone (sensitivity: 72.7%, 95% CI: 60.4-83.0; specificity: 52.6%, 95% CI: 40.9-64.0). CONCLUSION:Idiopathic recurrent miscarriage was associated with lower basal estradiol and anti-Mullerian hormone levels compared to explained recurrent miscarriage

Prognostic Laboratory Parameters in Placental Abruption: A Retrospective Case-Control Study

To evaluate routine laboratory parameters in women with and without placental abruption (PA) and in controls, 417 women were included in this retrospective cohort study in a tertiary-care center. 118 women with PA (Group A: 54 without vaginal bleeding and Group B: 64 with bleeding), 130 women without either PA or vaginal bleeding throughout their pregnancy (Group C), 123 women with vaginal bleeding but without PA (Group D), and 46 healthy pregnant women who had undergone a control laboratory evaluation in the second/third trimester for history of previous cytomegalovirus (additional control group) were included. Hemoglobin, leukocytes, thrombocytes, C-reactive protein (CRP), and fibrinogen were obtained within 48 h before C-section and/or at the time of bleeding onset. Cases (Groups A and B) revealed higher CRP levels than controls (Groups C and D) after multivariate analysis in the sub-analyses of bleeding (0.56 mg/dL, interquartile range (IQR) 0.28&#8211;1.24 vs. 0.51 mg/dL, IQR 0.28&#8211;0.84; odds ratio (OR) 1.108, p = 0.006) and non-bleeding women (0.64 mg/dL, IQR 0.48&#8211;1.08 vs. 0.32 mg/dL, IQR 0.18&#8211;0.61; OR 7.454, p &lt; 0.001). The non-bleeding cases (Group A) revealed significantly higher leukocyte (12.01 g/L, IQR 9.41&#8211;14.10 vs. 9.21 g/L, IQR 7.95&#8211;10.49; OR 1.378, 95% confidence interval (CI): 1.095&#8211;1.735; p = 0.006) and CRP levels (0.64 mg/dL, IQR 0.48&#8211;1.08 vs. 0.33 mg/dL, IQR 0.20&#8211;0.50; OR 7.942, 95% CI: 1.435&#8211;43.958; p = 0.018) than the additional control group. In cases, none of the laboratory parameters differed between women with and without bleeding. The significantly increased CRP levels found for women with PA and the lack of a difference in CRP between bleeding and non-bleeding cases point toward a chronic process underlying placental abruption. However, this laboratory parameter does not seem clinically relevant for distinguishing between women with and without placental abruption at this point in time

Cervical length dynamics in triplet pregnancies : a retrospective cohort study

Purpose To review our experience with a screening program that included sequential cervical length measurements in our large population of triplet pregnancies. Methods Seventy-eight triplet pregnancies were retrospectively included. Cervical length measurements were performed by transvaginal ultrasound in 2-week intervals from week 16 + 0 onwards in a tertiary-care center in Vienna. The main outcome measurement was preterm delivery prior to 32 + 0 weeks of gestation. Statistical analyses were performed using paired and unpaired t tests and a stepwise linear regression model. Results There were 26 cases of preterm delivery (33.3%). Women with preterm delivery revealed significant cervical length shortening from week 22 + 0 (median 33 mm, interquartile range, IQR 1739) to 24 + 0 (median 21 mm, IQR 730; p = 0.005). This was not observed in women without preterm delivery. From week 22 + 0 onwards, both groups showed further significant 2-week differences in cervical length (p < 0.05). Univariate analysis of cervical length in weeks 20 + 0, 22 + 0, and 24 + 0 as well as cervical length dynamics from 22 + 0 to 24 + 0 predicted preterm delivery. Conclusions In triplet pregnancies, a decrease in cervical length seems physiological from week 22 + 0 onwards. A sharp decrease in cervical length from the 22 + 0 to the 24 + 0 week as well as the smaller cervical length in weeks 20 + 0, 22 + 0, and 24 + 0 increase the risk of preterm delivery.(VLID)355042

Anti-Mullerian hormone is linked to the type of early pregnancy loss in idiopathic recurrent miscarriage: a retrospective cohort study

Abstract We correlated Anti-Mullerian hormone (AMH) levels and other parameters for ovarian reserve to the gestational age at the time of pregnancy loss in women with idiopathic recurrent miscarriage. In a retrospective study, 79 patients had suffered a total of 266 miscarriages. When comparing women with an “unembryonic” to those with an “embryonic” most recent miscarriage, there was no difference in median age (36.3 years, IQR 31.6–40.1 versus 34.2 years, IQR 29.9–38.0; p = 0.303) but in median AMH levels (0.7, IQR 0.2–18, versus median 1.8, IQR 1.3–3.3, respectively, p = 0.044) and in the rate of patients with an AMH ≤ 1 ng/mL (23/37, 62.2%, versus 8/42, 19%; p < 0.001). Thus, AMH might add to the diagnostic process in recurrent miscarriage in the future

Intra- versus retroplacental hematomas: a retrospective case-control study on pregnancy outcomes

Abstract Background Intrauterine hematomas are a common pregnancy complication. The literature lacks studies about outcomes based on hematoma localization. Thus, we aimed to compare pregnancies complicated by an intraplacental hematoma to cases with a retroplacental hematoma and to a control group. Methods In a retrospective case-control study, 32 women with an intraplacental hematoma, 199 women with a retroplacental hematoma, and a control group consisting of 113 age-matched women with no signs of placental abnormalities were included. Main outcome measures were pregnancy complications. Results Second-trimester miscarriage was most common in the intraplacental hematoma group (9.4%), followed by women with a retroplacental hematoma (4.2%), and controls (0%; p = 0.007). The intraplacental hematoma group revealed the highest rates for placental insufficiency, intrauterine growth retardation, premature preterm rupture of membranes, preterm labor, preterm delivery <37 weeks, and early preterm delivery <34 weeks (p < 0.05), followed by the retroplacental hematoma group. When tested in multivariate models, intraplacental hematomas were independent predictors for placental insufficiency (ß = 4.19, p < 0.001) and intrauterine growth restriction (ß = 1.44, p = 0.035). Intrauterine fetal deaths occurred only in women with a retroplacental hematoma (p = 0.042). Conclusions Intra- and retroplacental hematomas have different risk profiles for the affected pregnancy and act as independent risk factors