The impact of p16ink4a positivity in invasive vulvar cancer on disease-free and disease-specific survival, a retrospective study.

PURPOSE: To evaluate HPV and p16ink4a 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 p16ink4a status were evaluated in the context of a global multicenter trial. Logistic regression models were performed to identify the impact of p16ink4a positivity. RESULTS: 135 patients were included in the analysis. 32 (23.7%) showed a p16ink4a expression of over 25%. Disease-free and disease-specific survival was longer in p16ink4a positive patients (23 vs. 10 months, p = 0.004, respectively, 29 vs. 21 months, p = 0.016). In multivariate analysis, p16ink4a 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 p16ink4a positive invasive vulvar cancer.

Oligomannosidic glycans at Asn-110 are essential for secretion of human diamine oxidase.

N-Glycosylation plays a fundamental role in many biological processes. Human diamine oxidase (hDAO), required for histamine catabolism, has multiple N-glycosylation sites, but their roles, for example in DAO secretion, are unclear. We recently reported that the N-glycosylation sites Asn-168, Asn-538, and Asn-745 in recombinant hDAO (rhDAO) carry complex-type glycans, whereas Asn-110 carries only mammalian-atypical oligomannosidic glycans. Here, we show that Asn-110 in native hDAO from amniotic fluid and Caco-2 cells, DAO from porcine kidneys, and rhDAO produced in two different HEK293 cell lines is also consistently occupied by oligomannosidic glycans. Glycans at Asn-168 were predominantly sialylated with bi- to tetra-antennary branches, and Asn-538 and Asn-745 had similar complex-type glycans with some tissue- and cell line-specific variations. The related copper-containing amine oxidase human vascular adhesion protein-1 also exclusively displayed high-mannose glycosylation at Asn-137. X-ray structures revealed that the residues adjacent to Asn-110 and Asn-137 form a highly conserved hydrophobic cleft interacting with the core trisaccharide. Asn-110 replacement with Gln completely abrogated rhDAO secretion and caused retention in the endoplasmic reticulum. Mutations of Asn-168, Asn-538, and Asn-745 reduced rhDAO secretion by 13, 71, and 32%, respectively. Asn-538/745 double and Asn-168/538/745 triple substitutions reduced rhDAO secretion by 85 and 94%. Because of their locations in the DAO structure, Asn-538 and Asn-745 glycosylations might be important for efficient DAO dimer formation. These functional results are reflected in the high evolutionary conservation of all four glycosylation sites. Human DAO is abundant only in the gastrointestinal tract, kidney, and placenta, and glycosylation seems essential for reaching high enzyme expression levels in these tissues.

Heavy black tea consumption and elevated CA 19-9 and CA 125 levels. A case report on a patient with ovarian endometriotic cysts.

In this case report, we present a case of false positive CA 19-9 and CA 125 levels in a patient with suspected endometriotic cysts. The patient is a 34-year-old nulliparous woman with heavy black tea consumption and elevated CA 19-9 and CA 125 levels. After discontinuation of black tea intake and careful exploration of other possible factors, CA 19-9 and CA 125 levels dropped markedly. As a conclusion, heavy black tea consumption can lead to false positive results of elevated CA 19-9 and CA 125 levels.

Risk-adapted management for vasa praevia: a retrospective study about individualized timing of caesarean section.

PURPOSE: Vasa praevia is a rare condition with high foetal mortality if not detected prenatally. There is limited evidence available to determine the ideal timing of delivery and management recommendations. The aim of this study was to critically review our experience with vasa praevia, with a focus on diagnosis and management. METHODS: In a retrospective analysis, all cases of vasa praevia identified in our department from January 2003 to December 2017 were included. All cases were diagnosed antenatally during sonographic inspection of the placenta, and individualized management for each patient was performed based on individual risk factors. 19 cases of vasa praevia were identified (15 singletons, four twins). 13 patients (79%) presented placental anomalies. In patients at high risk for preterm birth, caesarean delivery was performed between 34-35 weeks after early hospitalization and administration of corticosteroids, whereas in patients at low risk for preterm birth, caesarean section could be delayed to 35-37 weeks of gestation. Administration of corticosteroids was not obligatory in the latter cases. RESULTS: There were two acute caesarean sections, due to premature abruption of the placenta and vaginal bleeding. There was no maternal or foetal/neonatal death. None of the neonates required blood transfusion. There is limited evidence available with which to determine the ideal timing of delivery. CONCLUSION: However, our individualized, risk-adapted management, which attempts to delay the timing of caesarean section up to two weeks beyond the standard recommendation, seems feasible, with just two emergency caesarean sections and no case of foetal or maternal death.

Does anti-Mullerian hormone predict the outcome of further pregnancies in idiopathic recurrent miscarriage? A retrospective cohort study.

PURPOSE: To evaluate whether anti-Mullerian hormone, basal follicle-stimulating hormone, luteinizing hormone, estradiol, and female age would predict future outcomes in women with idiopathic recurrent miscarriage. METHODS: One hundred and sixteen women with idiopathic recurrent miscarriage were retrospectively included. Luteal support with or without a combined treatment regimen for idiopathic recurrent miscarriage was applied in a tertiary-care center in Vienna. Occurrence and outcome of further pregnancies were analyzed. RESULTS: Within a median follow-up duration of 42.3 months, 94 women (81.0%) achieved one or more pregnancies. Further miscarriages occurred in 47 patients in whom only a higher number of previous miscarriages was predictive (OR 3.568, 95% CI 1.457-8.738; p = 0.005). Fifty-seven women had a live birth > 23 + 0 gestational weeks. In a multivariate analysis, age (OR 0.920, 95% CI 0.859-0.986; p = 0.019) and the number of previous miscarriages (OR 0.403, 95% CI 0.193-0.841; p = 0.016), but not AMH (OR 1.191, 95% CI 0.972-1.461; p = 0.091) were significantly predictive. CONCLUSION: AMH seems of either no or only minor relevance for the prediction of further miscarriages and live birth in women with idiopathic recurrent miscarriage.

Reliability of sonographic fetal weight estimation in triplet pregnancies: a retrospective cohort study.

PURPOSE: To review our experience in ultrasound fetal weight estimation in our large population of triplet pregnancies. METHODS: Ninety-seven triplet pregnancies were retrospectively included between January 2003 and January 2017. Sonographic fetal weight estimation using Hadlock's and Schild's formulas was compared to actual birth weight in a tertiary-care center in Vienna, Austria. Statistical analyses were performed using a stepwise linear regression model and crosstabs. RESULTS: The median discrepancy between the sonographically estimated fetal weight by Hadlock's formula and the actual birth weight was 106 g (IQR 56-190). The percentage error and its standard deviation were - 2.5 ± 12.1%, and the median percentage error was - 3.6%. Concerning the use of Hadlock's formula, estimated fetal weight was the most important factor predictive of actual birth weight with an estimate of 0.920 (p < 0.001). Female neonates had been overestimated by a mean of 50.473 g per fetus. The sonographic prediction of small-for-gestational-age neonates was significantly reliable (p < 0.001), with positive and negative predictive values ranging from 81.3 to 100.0%. Similar results were obtained for Schild's formula. CONCLUSION: Even if sonographically estimated fetal weight in triplet pregnancies has a high overall accuracy of fetal weight estimation, there are some limitations in prediction of intrauterine growth restrictions, especially in female fetuses.

Altered glucose profiles and risk for hypoglycaemia during oral glucose tolerance testing in pregnancies after gastric bypass surgery.

AIMS/HYPOTHESIS: A history of gastric bypass surgery can influence the results of the OGTT recommended during pregnancy. Therefore, we compared OGTT glucose kinetics and pregnancy outcome between pregnant gastric bypass patients and BMI-matched, lean and obese controls. METHODS: Medical records were used to collect data on glucose measurements during the 2 h 75 g OGTT as well as on pregnancy and fetal outcome for 304 women (n = 76 per group, matched for age and date of delivery). RESULTS: Women after bariatric surgery had lower fasting glucose levels compared with lean, obese and BMI-matched controls, and showed altered postprandial glucose kinetics, including a rise at 60 min followed by hypoglycaemia with serum glucose of <3.34 mmol/l (which occurred in 54.8%). Moreover, their risk of pre-eclampsia or gestational hypertension was reduced, with an increased risk of delivering small for gestational age infants. CONCLUSIONS/INTERPRETATION: Alternative strategies to accurately define impaired glucose metabolism in pregnancies after bariatric surgery should be explored.

Extravillous trophoblast invasion of venous as well as lymphatic vessels is altered in idiopathic, recurrent, spontaneous abortions.

STUDY QUESTION: Do extravillous trophoblasts (EVTs) invade non-arterial decidual vessels in healthy and pathological pregnancies? SUMMARY ANSWER: Our results reveal that trophoblast invasion of venous and lymphatic vessels is a frequent event during the first trimester of pregnancy and is compromised in  recurrent spontaneous abortion (RSA). In addition, the present data suggest that EVTs populate regional lymph nodes during pregnancy. WHAT IS ALREADY KNOWN: Human trophoblasts remodel and invade decidual spiral arteries. In addition, a recent report demonstrates that trophoblasts contact and invade decidual veins. STUDY DESIGN, SIZE, DURATION: Tissue samples of human first trimester deciduae basalis (n = 54, 6th-13th weeks of gestation) obtained from elective pregnancy terminations were used to study trophoblast invasion into veins and lymphatics, in comparison to arteries. Age-matched cases of idiopathic, recurrent spontaneous abortions tissue samples (n = 23) were assessed for cell numbers of EVTs in these decidual vessels. In addition, lymph nodes of four pregnant women were analysed for the presence of EVTs. PARTICIPANTS/MATERIALS, SETTING, METHODS: Localization, frequency and EVT-mediated targeting and invasion of arterial, venous as well as lymphatic vessels were determined in first trimester decidua basalis tissue sections using immunofluorescence staining with antibodies against CD31, CD34, ephrin B2 (EFNB2), ephrin receptor B4 (EPHB4), HLA-G, podoplanin, prospero-related homeobox 1 (Prox-1), alpha-smooth muscle actin 2 (ATCTA2), von willebrand factor (vWF) and proteoglycan 2 (PRG2). Arterial, venous and lymphatic-associated EVTs were further characterized according to their position in the vascular structure and classified as intramural (im) or intraluminal (il). MAIN RESULTS AND THE ROLE OF CHANCE: EVTs, specifically expressing PRG2, target and invade veins and lymphatics in first trimester decidua basalis since HLA-G+ trophoblast were detected in the vascular wall (intramural EVT, imEVTs) and in the lumen of these vessels (intraluminal EVT, ilEVTs). In total, 276 arteries, 793 veins and 113 lymphatics were analysed. While EVTs contact and invade arteries and veins to a similar extent we found that lymphatics are significantly less affected by EVTs (P = 0.001). Moreover, ilEVTs were detected in the lumen of venous and lymphatic vessels, whereas ilEVTs were only found occasionally in the lumen of arteries. Interestingly, RSA tissue sections contained significantly more arterial (P = 0.037), venous (P = 0.002) and lymphatic vessels (P < 0.001), compared to healthy controls. However, while RSA-associated arterial remodeling was unchanged (P = 0.39) the ratios of EVT-affected versus total number of veins (P = 0.039) and lymphatics (P < 0.001) were significantly lower in RSA compared to age-matched healthy decidual sections. Finally, HLA-G+/PRG2+/CD45-EVTs can be detected in regional lymph nodes of pregnant women diagnosed with cervical cancer. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In this study, first trimester decidual tissues from elective terminations of pregnancies have been examined and used as a reference for healthy pregnancy. However, this collective may also include pregnancies which would have developed placental disorders later in gestation. Due to limitations in tissue availability our staining results for EVT-specific marker expression in regional lymph nodes of pregnant women are based on four cases only. WIDER IMPLICATIONS OF THE FINDINGS: In this study, we propose migration of HLA-G+ cells into regional lymph nodes during pregnancy suggesting that the human EVT is capable of infiltrating maternal tissues via the blood stream. Moreover, the description of compromised EVT invasion into the venous and lymphatic vasculature in RSA may help to better understand the pathological characteristics of idiopathic recurrent pregnancy loss. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Austrian Science Fund (grant P-25187-B13 to J.P. and grant P-28417-B30 to M.K.). There are no competing interests to declare.

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

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.

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.

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 17-39) to 24 + 0 (median 21 mm, IQR 7-30; 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.

The predictive value of sequential cervical length screening in singleton pregnancies after cerclage: a retrospective cohort study.

BACKGROUND: There are few valid predictors for preterm delivery after cerclage. Experience with a screening program that included four sequential cervical length measurements in singleton pregnancies after cerclage is reviewed. METHODS: In this retrospective cohort study, 88 singleton pregnancies after cerclage were included. Cervical length (CL) measurements were performed perioperatively and at weeks 16 + 0, 18 + 0, 20 + 0, and 22 + 0 by transvaginal ultrasound. Predictive factors for early preterm delivery included patient characteristics, obstetric history and CL measurements and were analyzed separately for women with ultrasound-indicated cerclage and those with history-indicated cerclage. Women with emergency cerclage were excluded. RESULTS: In women with delivery <35 weeks, CL declined from the 16 + 0 to the 22 + 0 weeks of gestation (p = 0.009). In univariate analysis, all CL measurements were predictive for delivery <35 weeks in women who underwent ultrasound-indicated cerclage and in women who received a history-indicated cerclage, whereas in multivariate analysis only CL three to six days after cerclage remained significant (odds ratio 0.85, 95% CI 0.73-0.98). In women with ultrasound-indicated cerclage, optimized cut-off was ≤ 20 mm (specificity 83.8%, sensitivity 84.2%). CONCLUSIONS: CL measured three to six days after cerclage placement provides the best information about the risk for delivery <35 weeks.

Acetylic Salicylic Acid for the Treatment of Chronic Obstructive Pulmonary Disease: A Randomized, Double-Blind, Placebo-Controlled Trial.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death in the world. Current treatment options provide relief from symptoms rather than stop disease progress. Results from various preclinical experiments suggest a causal benefit of acetylic salicylic acid (ASA) in the treatment of COPD. Hence, this study set out to examine the clinical benefit of ASA in the treatment of COPD. COPD patients (Global Initiative for Chronic Obstructive Lung Disease II-III) received either once daily 500 mg of ASA or a matching placebo for 12 weeks in addition to their preexisting medication. Clinical response in terms of pulmonary function testing, symptomatic response and adverse events were assessed. After 40 subjects were included, the study was stopped and an interim analysis was performed. The addition of ASA to the treatment of subjects with COPD had no effect on clinical features or spirometry (forced expiratory volume in 1 s: F = 0.49, d.f.1 = 1, d.f.2 = 74, p = 0.486) and non-pulmonary markers. COPD represents a complex of different diseases, although currently classified mainly by markers of lung function. If future trials test the effects of anti-inflammatory therapies, COPD subpopulations should be predefined based on inflammatory features.

Velamentous cord insertion as a risk factor for obstetric outcome: a retrospective case-control study.

PURPOSE: Velamentous umbilical cord insertion (VCI) is associated with adverse pregnancy outcomes. Literature lacks data on Doppler. We aimed to evaluate obstetric outcomes and results of uterine and umbilical artery Doppler flowmetry associated with VCI. MATERIALS AND METHODS: In a retrospective case-control study, 108 singleton pregnancies with VCI were age- and body mass index-matched to 108 singleton pregnancies without VCI. The main outcome parameters were obstetric outcome, pregnancy-related complications, uterine artery flowmetry at the second-trimester screening, and umbilical artery flowmetry before delivery. Statistical analysis was accomplished using Pearson's Chi-square test or Fisher's exact test, and the Mann-Whitney U test, where appropriate. RESULTS: Pregnancies with VCI revealed a significantly higher PI in the umbilical artery during the last measurement before delivery (1.00 ± 0.25 vs. 0.90 ± 0.10; p = 0.001). Gestational age at this measurement did not differ between the groups. Fetal malformations and intrauterine fetal death were more common in pregnancies with VCI (12.7 vs. 0 %; p < 0.001, and 6.5 vs. 0 %; p = 0.014, respectively). Patients with VCI delivered significantly earlier (36.2 ± 4.5 vs. 38.4 ± 2.6; p < 0.001). CONCLUSION: Higher rates of (early) preterm delivery were found in pregnancies with VCI. Fetuses with VCI also suffered from malformations and IUFD more frequently. The last pulsatility index value in the umbilical artery, before delivery, was significantly higher in pregnancies with VCI, which is of uncertain clinical value.

Association of -463G/A MPO gene polymorphism and risk of cervical intraepithelial neoplasia.

PURPOSE: The MPO system plays an important role in the control of infections and the deletion of malignant cells. Nevertheless, alternations in the MPO system can lead to DNA damage and carcinogenesis. Polymorphisms in the MPO Gene have been associated with an increased expression of MPO and a higher risk for development of cancer. This study evaluates the association between -463G/A MPO gene polymorphism and the risk for CIN. METHODS: The MPO gene polymorphism (-463G/A) was investigated in 616 women with cervical intraepithelial neoplasia and in 206 healthy women. Association between MPO gene polymorphism and risk of cervical intraepithelial neoplasia were analyzed by univariate and multivariable models. RESULTS: No significant difference in genotype distribution of the MPO gene polymorphism was observed in women with CIN and controls (p = 0.4; OR 1.2, 95 % CI 0.8-1.6). A subgroup analysis only including women with CIN did not show an association between -463G/A MPO gene polymorphism and risk for high-grade CIN (CIN 2/3) (p = 0.09; OR 1.5, 95 % CI 0.9-2.3). CONCLUSIONS: The investigated MPO gene polymorphism is not associated with risk for the development of cervical intraepithelial neoplasia.

A retrospective study on perineal lacerations in vaginal delivery and the individual performance of experienced mifwives.

BACKGROUND: Medical staff's influence on patient outcomes has become a subject of interest. We evaluated experienced midwives and compared their performance concerning perineal lacerations (PL). METHODS: In a retrospective cohort study, 1937 women with singleton pregnancies who had delivered spontaneously with a cephalic presentation by experienced midwives in the Medical University of Vienna from January 2009 to April 2014 were included. As predictive parameters, we included basic patient-, pregnancy- and delivery-related characteristics including the individual midwife who delivered the child. The incidence of PL was the main outcome measure. RESULTS: Overall PL and severe PL were found in 508/1937 (26.2%) and 19/1937 women (1.0%), respectively. In a multivariate analysis for PL of any degree, maternal age (ß = 0.170 ± 0.080), gestational age at delivery (ß = 0.190 ± 0.320), and birth weight (ß = 0.002 ± 0.000) significantly increased the risk, whereas multiparity (ß = -0.379 ± 0.141) and mediolateral episiotomy (ß = -1.514 ± 0.284) decreased it (p < 0.05). In addition, the individual midwife who delivered the child was a significant influencing factor, with ß-values ranging from -0.028 to 0.899 compared to the reference midwife. For severe PL, the midwife was not of significant influence. CONCLUSIONS: The individual midwife is an independent factor that influences the risk for overall PL, not for severe PL. Other risk factors include maternal age, gestational age at delivery, birth weight, parity and episiotomy.

What do women with gynecologic cancer know about HPV and their individual disease? A pilot study.

BACKGROUND: The vaccinations against human papilloma virus (HPV) are highly effective in preventing persistent infection. The level of knowledge about HPV and the consequences of an infection with this virus are low in the general population and in patients who suffer from HPV-associated diseases. We aimed to compare the level of knowledge about HPV and about the women's individual malignant disease between women with and without HPV-associated gynecologic cancer as well as the knowledge about individual malignant diseases. METHODS: In a pilot study, 51 women with HPV-related cancer (cervical cancer: n=30; vulvar or vaginal cancer: n=21) and 60 women with non-HPV associated gynecologic malignancies (ovarian cancer: n=30; endometrial cancer, n=30) were included. They answered a questionnaire including questions about personal medical history, risk factors for cancer development, and HPV. RESULTS: The general level of knowledge of the term "HPV" was low (29.7%, 33/111) and it was similar in patients with HPV-related and non-HPV-associated cancer (18/60, 30.0% vs. 15/51, 29.4%, respectively; p=1.000). When asked about their disease, 80% (24/30) of women with ovarian cancer correctly named their diagnosis, followed by women with cervical cancer (73.3%, 22/30), endometrial cancer (70%, 21/30) and vaginal or vulvar cancer (42.9%, 9/21; p=0.008). CONCLUSION: The level of knowledge about HPV and the malignant diseases the patient suffered from was low. This applied even to patients with HPV associated malignancies.

The prognostic value of estrogen receptor beta and proline-, glutamic acid- and leucine-rich protein 1 (PELP1) expression in ovarian cancer.

BACKGROUND: Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), a coregulator of the estrogen receptors (ERs) alpha and beta, is a potential proto-oncogene in hormone dependent gynecological malignancies. To better understand the role of PELP1 in epithelial ovarian cancer (EOC), the protein expression and prognostic significance of PELP1 was evaluated together with ERalpha and ERbeta in EOC tissues. METHODS: The expression of PELP1, ERalpha, and ERbeta was characterized in tumor tissues of 63 EOC patients. The prognostic value was calculated performing log-rank tests and multivariate Cox-Regression analysis. In a second step, validation analysis in an independent set of 86 serous EOC patients was performed. RESULTS: Nuclear PELP1 expression was present in 76.2% of the samples. Prevalence of PELP1 expression in mucinous tumors was significantly lower (37.5%) compared to serous (85.7%) and endometrioid tumors (86.7%). A significant association between PELP1 expression and nuclear ERbeta staining was found (p=0.01). Positive PELP1 expression was associated with better disease-free survival (DFS) (p=0.004) and overall survival (OS) (p=0.04). The combined expression of ERbeta+/PELP1+ revealed an independent association with better DFS (HR 0.3 [0.1-0.7], p=0.004) and OS (HR 0.3 [0.1-0.7], p=0.005). In the validation set, the combined expression of ERbeta+/PELP1+ was not associated with DFS (HR 0.7 [0.4-1.3], p=0.3) and OS (HR 0.7 [0.3-1.4], p=0.3). CONCLUSION: Positive immunohistochemical staining for the ER coregulator PELP1, alone and in combination with ERbeta, might be of prognostic relevance in EOC.

Impact of conization type on the resected cone volume: results of a retrospective multi-center study.

PURPOSE: The extent of conization seems to influence the risk of preterm birth. The aim of this study was to compare the cone volume after surgical resection with large loop excision of the transformation zone (LLETZ) and cold knife conization (CKC). METHODS: The present retrospective multi-center study comprises 804 consecutive women, who underwent LLETZ (n = 412) or CKC (n = 392) between 2004 and 2009. Univariate and multivariable analyses were performed to compare cone volumes removed by LLETZ and CKC and identify independent risk factors for large cone volume. RESULTS: The median resected cone volume after LLETZ was significantly smaller [1.6 cm(3) (0.8-2.9)] than after CKC [2.1 cm(3) (1.4-3.5)] (<0.0001). Complete resection rates were comparable in both groups. Conization method, cone depth, and institution type were independent risk factors for removal of a large cone volume. CONCLUSION: CKC removes larger cone volumes than LLETZ without the advantage of higher complete resection rates.

Rate of Involved Endocervical Margins According to High-Risk Human Papillomavirus Subtype and Transformation Zone Type in Specimens with Cone Length ≤ 10 mm versus > 10 mm-A Retrospective Analysis.

The aim of this study was to evaluate the endocervical margin status according to transformation zone (TZ) and high-risk HPV (hr-HPV) subtype in specimens with cone length ≤ 10 mm versus > 10 mm to provide data for informed decision making and patients counseling especially for women wishing to conceive. In this retrospective cohort study, 854 patients who underwent large loop excision of the transformation zone during a nine-year period (2013-2021) for cervical disease were analyzed. The main outcome parameters were excision length, histological result, TZ type, HPV subtype and endocervical margin status. A subgroup analysis was performed according to excision length, with a cut-off value of 10 mm. A two-step surgical procedure was performed in case of an excision length of > 10 mm. The overall rate of positive endocervical margins irrespective of excision length was 17.2%, with 19.3% in specimens with ≤ 10 mm and 15.0% with > 10 mm excision length. Overall, 41.2% of women with a visible TZ and HPV 16/hr infection and 27.0% of women with HPV 18 received an excisional treatment of > 10 mm length without further oncological benefit, respectively. In contrast, assuming that only an excision of ≤ 10 mm length had been performed in women with visible TZ, the rate of clear endocervical margins would have been 63.7% for HPV 16/hr infections and 49.3% for HPV 18 infections. In conclusion, the decision about excision length should be discussed with the patient in terms of oncological safety and the risk of adverse pregnancy events. An excision length > 10 mm increases the number of cases with cervical tissue removed without further oncological benefit, which needs to be taken into account in order to provide an individual therapeutic approach. Furthermore, HPV 18 positivity is related to a higher rate of positive endocervical margins irrespective of TZ.