Characterization of patients with vulvar lichen sclerosus and association to vulvar carcinoma: a retrospective single center analysis.

PURPOSE: Lichen sclerosus (LS) is a benign, cutaneous, chronic inflammatory (autoimmunological) disease. The differentiated vulvar intraepithelial neoplasia (dVIN) accounts for a precursor lesion of vulvar squamous cell carcinoma and is often associated with lichen sclerosus. Although the association between lichen sclerosus and vulvar carcinoma has long been recognized, there is a lack of evidence in literature. METHODS: This retrospective study examined pseudonymized data of 499 women diagnosed with vulvar pathology between 2008 and 2020 at the Department of Gynaecology and Obstetrics of Hannover Medical School (MHH). Data were further stratified for the time of onset, location of disease, accompanying disease, HPV status and progression of disease into vulvar squamous cell carcinoma (VSCC). RESULTS: In total, 56 patients were diagnosed with vulvar lichen sclerosus. The mean onset of disease was at 60.3 years of age. After subdividing cases of diagnosed LS into those who did not develop vulvar carcinoma in their course and those who did, the ages at onset are 52.66 ± 17.35 and 68.41 ± 10.87, respectively. The incidence of vulvar cancer in women diagnosed with lichen sclerosus was 48.2%. Twenty-five patients reported a diagnosis of VIN in their self-reported history. CONCLUSIONS: In our retrospective study, we showed a trend between vulvar lichen sclerosus and VSCC. The difference between the two age groups of patients diagnosed with lichen sclerosus who developed vulvar carcinoma and those who did not is statistically significant. Our results highlight the importance to diagnose lichen sclerosus early to ensure adequate follow-up and prevent progression to VSCC.

Perioperative morbidity of different operative approaches in early cervical carcinoma: a systematic review and meta-analysis comparing minimally invasive versus open radical hysterectomy.

PURPOSE: Radical hysterectomy and pelvic lymphadenectomy is the standard treatment for early cervical cancer. Studies have shown superior oncological outcome for open versus minimal invasive surgery, but peri- and postoperative complication rates were shown vice versa. This meta-analysis evaluates the peri- and postoperative morbidities and complications of robotic and laparoscopic radical hysterectomy compared to open surgery. METHODS: Embase and Ovid-Medline databases were systematically searched in June 2020 for studies comparing robotic, laparoscopic and open radical hysterectomy. There was no limitation in publication year. Inclusion criteria were set analogue to the LACC trial. Subgroup analyses were performed regarding the operative technique, the study design and the date of publication for the endpoints intra- and postoperative morbidity, estimated blood loss, hospital stay and operation time. RESULTS: 27 studies fulfilled the inclusion criteria. Five prospective, randomized-control trials were included. Meta-analysis showed no significant difference between robotic radical hysterectomy (RH) and laparoscopic hysterectomy (LH) concerning intra- and perioperative complications. Operation time was longer in both RH (mean difference 44.79 min [95% CI 38.16; 51.42]), and LH (mean difference 20.96 min; [95% CI - 1.30; 43.22]) than in open hysterectomy (AH) but did not lead to a rise of intra- and postoperative complications. Intraoperative morbidity was lower in LH than in AH (RR 0.90 [0.80; 1.02]) as well as in RH compared to AH (0.54 [0.33; 0.88]). Intraoperative morbidity showed no difference between LH and RH (RR 1.29 [0.23; 7.29]). Postoperative morbidity was not different in any approach. Estimated blood loss was lower in both LH (mean difference - 114.34 [- 122.97; - 105.71]) and RH (mean difference - 287.14 [- 392.99; - 181.28]) compared to AH, respectively. Duration of hospital stay was shorter for LH (mean difference - 3.06 [- 3.28; - 2.83]) and RH (mean difference - 3.77 [- 5.10; - 2.44]) compared to AH. CONCLUSION: Minimally invasive radical hysterectomy appears to be associated with reduced intraoperative morbidity and blood loss and improved reconvalescence after surgery. Besides oncological and surgical factors these results should be considered when counseling patients for radical hysterectomy and underscore the need for new randomized trials.

Protective operative techniques in radical hysterectomy in early cervical carcinoma and their influence on disease-free and overall survival: a systematic review and meta-analysis of risk groups.

PURPOSE: Radical hysterectomy with pelvic lymphadenectomy presents the standard treatment for early cervical cancer. Recently, studies have shown a superior oncological outcome for open versus minimal invasive surgery, however, the reasons remain to be speculated. This meta-analysis evaluates the outcomes of robotic and laparoscopic hysterectomy compared to open hysterectomy. Risk groups including the use of uterine manipulators or colpotomy were created. METHODS: Ovid-Medline and Embase databases were systematically searched in June 2020. No limitation in date of publication or country was made. Subgroup analyses were performed regarding the surgical approach and the endpoints OS and DFS. RESULTS: 30 studies fulfilled the inclusion criteria. Five prospective, randomized-control trials were included. Patients were analyzed concerning the surgical approach [open surgery (AH), laparoscopic surgery (LH), robotic surgery (RH)]. Additionally, three subgroups were created from the LH group: the LH high-risk group (manipulator), intermediate-risk group (no manipulator, intracorporal colpotomy) and LH low-risk group (no manipulator, vaginal colpotomy). Regarding OS, the meta-analysis showed inferiority of LH in total over AH (0.97 [0.96; 0.98]). The OS was significantly higher in LH low risk (0.96 [0.94; 0.98) compared to LH intermediate risk (0.93 [0.91; 0.94]). OS rates were comparable in AH and LH Low-risk group. DFS was higher in the AH group compared to the LH group in general (0.92 [95%-CI 0.88; 0.95] vs. 0.87 [0.82; 0.91]), whereas the application of protective measures (no uterine manipulator in combination with vaginal colpotomy) was associated with increased DFS in laparoscopy (0.91 [0.91; 0.95]). CONCLUSION: DFS and OS in laparoscopy appear to be depending on surgical technique. Protective operating techniques in laparoscopy result in improved minimal invasive survival.

Psychological distress in cervical cancer screening: results from a German online survey.

PURPOSE: The PODCAD study aimed at assessing the degree of psychological stress that women experience due to notification of an abnormal Papanicolaou (Pap) smear finding or a positive human papillomavirus (HPV) test result. METHODS: We designed a survey to address the question of psychological burden due to abnormal Pap smear results and/or positive HPV tests. In this online campaign approach, we aimed to reach > 2000 women all over Germany irrespective of kind and number of abnormal screening findings. We asked for different kinds of anxiety, distress and uncertainty regarding both, Pap and HPV status. RESULTS: A total of 3753 women completed the survey at least partially, and almost 2300 fully completed the survey. Of these, more than 50% were affected already since more than 1 year, and almost half of them had experienced at least three Pap smears in follow-up examinations. Almost 70% of the women were afraid of developing cancer. Intriguingly, almost half of the women with abnormal findings were not aware of their stage of the Pap smear. Furthermore, almost 30% of the women displayed signs of a post-traumatic stress disorder. CONCLUSION: Abnormal results in cervical cancer screening have an impact on patients' psychology, irrespective of the knowledge and severity of the findings. Better information concerning risks and benefits of cervical cancer screening and about the meaning of the outcome of its procedures are required to decrease this anxiety.

Array-comparative genomic hybridization analysis in patients with Müllerian fusion anomalies.

Fusion anomalies of the Müllerian ducts are associated with an increased risk for miscarriage and premature labor. In most cases polygenic-multifactorial inheritance can be assumed but autosomal-dominant inheritance with reduced penetrance and variable manifestation should be considered. We performed array-comparative genomic hybridization (CGH) analysis in a cohort of 103 patients with Müllerian fusion anomalies. In 8 patients we detected microdeletions and microduplications in chromosomal regions 17q12, 22q11.21, 9q33.1, 3q26.11 and 7q31.1. The rearrangement in 17q12 including LHX1 and HNF1ß as well as in 22q11.21 have already been observed in MRKHS (Mayer-Rokitansky-Küster-Hauser syndrome). In summary, we (1) detected causative micro-rearrangements in patients with Müllerian fusion anomalies, (2) show that Müllerian fusion anomalies and MRKHS may have a common etiology, and (3) identified new candidate genes for Müllerian fusion anomalies.

Morbidity, fertility and pregnancy outcomes after myoma enucleation by laparoscopy versus laparotomy.

OBJECTIVES: Myomas are defined as benign tumours that arise from smooth muscle cells of the uterus. Clinically, they are found in 5-77% of women of reproductive age. The prevalence rate varies considerably in the literature and a large number of fibroids do not cause symptoms. The lifetime risk of acquiring myomas is 70% for Caucasian women and ≥ 80% for African American women. MATERIALS/METHODS: The data of 265 patients undergoing surgery for symptomatic myomas by laparoscopy or laparotomy, performed in the gynaecological department of Hannover Medical School, Hannover, Germany, between 2009 and 2013, were retrospectively analysed in this retrospective design study. RESULTS: High pregnancy rates (up to 70%) and birth rates (up to 86%) after myomectomy, regardless of the surgical approach adopted, were found in the current study. The trend was that ≥ 3 myomas and those that were ≥ 6 cm in size were almost always removed by laparotomy in our clinic. It was possible to remove up to 42 myomas without having to perform a hysterectomy. A statistically significant negative correlation was observed in relation to the association between the size of the largest myoma extracted and the pregnancy rate (p = 0.02). A statistically significant correlation between the number of removed myomas and the pregnancy rate was observed for patients who wished to bear children (p = 0.010). Elevated complication rates (of up to 50%) were reported for more than three extracted myomas with a statistically significance (p = 0.0471). CONCLUSIONS: It is necessary to ensure sound preoperative selection of the surgical approach in order to achieve the most optimal results, especially for those patients who wished to bear children.

Estimation of neonatal outcome artery pH value according to CTG interpretation of the last 60 min before delivery: a retrospective study. Can the outcome pH value be predicted?

PURPOSE: The aim of this study was to analyze whether the umbilical artery pH value can be estimated throughout CTG assessment 60 min prior to delivery and if the estimated umbilical artery pH value correlates with the actual one. This includes analysis of correlation between CTG trace classification and actual umbilical artery pH value. Intra-and interobserver agreement and the impact of professional experience on visual analysis of fetal heart rate tracing were evaluated. METHODS: This was a retrospective study. 300 CTG records of the last 60 min before delivery were picked randomly from the computer database with the following inclusion criteria; singleton pregnancy >37 weeks, no fetal anomalies, vaginal delivery either spontaneous or instrumental-assisted. Five obstetricians and two midwives of different professional experience classified 300 CTG traces according to the FIGO criteria and estimated the postnatal umbilical artery pH. RESULTS: The results showed a significant difference (p < 0.05) in estimated and actual pH value, independent of professional experience. Analysis and correlation of CTG assessment and actual umbilical artery pH value showed significantly (p < 0.05) diverging results. Intra- and interobserver variability was high. Intraobserver variability was significantly higher for the resident (p = 0.001). No significant differences were detected regarding interobserver variability. CONCLUSION: An estimation of the pH value and consequently of neonatal outcome on the basis of a present CTG seems to be difficult. Therefore, not only CTG training but also clinical experience and the collaboration and consultation within the whole team is important.

Mutations in WNT9B are associated with Mayer-Rokitansky-Küster-Hauser syndrome.

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a well-known malformation pattern of the Müllerian ducts (MDs) characterized by congenital absence of the uterus and vagina. To date, most cases remain unexplained at molecular level. As female Wnt9b-/- mice show a MRKHS-like phenotype, WNT9B has emerged as a promising candidate gene for this disease. We performed retrospective sequence analyses of WNT9B in 226 female patients with disorders of the MDs, including 109 patients with MRKHS, as well as in 135 controls. One nonsense mutation and five likely pathogenic missense mutations were detected in WNT9B. Five of these mutations were found in cases with MRKHS accounting for 4.6% of the patients with this phenotype. No pathogenic mutations were detected in the control group (p = 0.017). Interestingly, all of the MRKHS patients with a WNT9B mutation were classified as MRKHS type 1, representing 8.5% of the cases from this subgroup. In previous studies, two of the patients with a WNT9B mutation were found to carry either an additional deletion of LHX1 or a missense mutation in TBX6. We conclude that mutations in WNT9B were frequently associated with MRKHS in our cohort and some cases may be explained by a digenic disease model.

Correlation of fetal scalp blood sampling pH with neonatal outcome umbilical artery pH value.

PURPOSE: Fetal scalp blood sampling is considered as a complimentary tool in addition to cardiotocography to assess fetal well-being. This blood sampling is important as the obstetrician has to judge and make decisions regarding the further management of the delivery based on this pH result. The aim of this study was to analyze the correlation between fetal scalp blood pH and the umbilical artery pH after birth. Furthermore, it was investigated whether tocolysis, a performed episiotomy or cord encirclement have an influence on the umbilical artery pH. METHODS: This retrospective study over a period of 11 years included all singleton pregnancies without fetal anomalies, which were monitored by fetal scalp blood sampling during labor. RESULTS: 844 out of 1502 deliveries were included for analysis. The analysis demonstrates a good correlation between fetal scalp pH value and outcome pH value. Subgroup analysis with fetal scalp blood pH <7.20 showed a difference in 40 of 82 cases, with an outcome pH value ≥7.20, but this difference was statistically insignificant. Neither did tocolysis, episiotomy or the presence of cord encirclement show an overall effect, nor did they have an impact on the subgroup. CONCLUSION: Obstetricians must consider that the values of fetal scalp blood are not always reliable and can be false. However, on the basis of CTG and fetal scalp blood pH, decisions are made regarding delivery interventions. Therefore, we would encourage the consideration of taking two samples routinely at every attempt of fetal blood sampling.

Background Knowledge and Attitude of Pregnant Women towards Ultrasound Screening at 20-23 Weeks Gestation.

BACKGROUND: Prenatal ultrasound screening in the second trimester is widely used in maternal health care. Prenatal diagnosis and prenatal screening is often exposed to several accusation, such as inducing unnecessary anxiety, carrying out a selection and forcing pregnant women into attending ultrasound screening. The aim of this study was to investigate the knowledge and the intention of pregnant women attending the second trimester ultrasound screening. PATIENTS AND METHODS: This was a prospective study. Women attending the 20 weeks anomaly scan were given an anonymous questionnaire to evaluate the background knowledge about the anomaly scan and their opinion about prenatal screening. RESULTS: 600 (96.7%) of 620 recruited women filled in the questionnaire completely. To the majority (>80%) of women it is important to exclude severe fetal anomalies and to secure normal fetal growth. The background knowledge of the women was good, but a clear supply of information and a detail counselling would improve the understanding, especially in the group of lower education. The majority of the women stated that the 20 weeks anomaly scan should be offered to every woman. CONCLUSION: Prenatal ultrasound examination is not only essential from a medical point of view for example for important information regarding the status of the fetus, but also has a major impact as a positive psychological factor for pregnant women.

Surgical staging and prognosis in serous borderline ovarian tumours (BOT): a subanalysis of the AGO ROBOT study.

BACKGROUND: Incomplete surgical staging is a negative prognostic factor for patients with borderline ovarian tumours (BOT). However, little is known about the prognostic impact of each individual staging procedure. METHODS: Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 at 24 German AGO centres were analysed. In 559 patients with serous BOT and adequate ovarian surgery, further recommended staging procedures (omentectomy, peritoneal biopsies, cytology) were evaluated applying Cox regression models with respect to progression-free survival (PFS). RESULTS: For patients with one missing staging procedure, the hazard ratio (HR) for recurrence was 1.25 (95%-CI 0.66-2.39; P=0.497). This risk increased with each additional procedure skipped reaching statistical significance in case of two (HR 1.95; 95%-CI 1.06-3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI 1.22-4.64; P=0.011). The most crucial procedure was omentectomy which retained a statistically significant impact on PFS in multiple analysis (HR 1.91; 95%-CI 1.15-3.19; P=0.013) adjusting for previously established prognostic factors as FIGO stage, tumour residuals, and fertility preservation. CONCLUSION: Individual surgical staging procedures contribute to the prognosis for patients with serous BOT. In this analysis, recurrence risk increased with each skipped surgical step. This should be considered when re-staging procedures following incomplete primary surgery are discussed.

SPECT/CT for SLN dissection in vulvar cancer: Improved SLN detection and dissection by preoperative three-dimensional anatomical localisation.

OBJECTIVE: In this study, we assessed the feasibility and clinical advantages of single photon emission computed tomography with CT (SPECT/CT) for sentinel lymph node (SLN) detection in vulvar cancer. METHODS: This is a unicentric prospective trial. Vulvar cancer patients underwent preoperative SLN marking (10MBq Technetium (TC)-99m-nanocolloid) and subsequent planar lymphoscintigraphy (LSG) and SPECT/CT for SLN visualization. Directly before surgery, a patent blue dye was injected. We assessed detection rates of SPECT/CT and those of planar LSG and intraoperative detection. We analyzed the sensitivity, negative predictive value and false negative rate. RESULTS: At Hannover Medical School, 40 vulvar cancer patients underwent SLN dissection after preoperative LSG and SPECT/CT. The mean diameter of all tumors in final histology was 2.23 (0.1-10.5) cm with a mean tissue infiltration of 3.93 (0.25-11) mm. In preoperative imaging, SPECT/CT identified significantly more SLNs (mean 8.7 (1-35) LNs per patient) compared to LSG (mean 5.9 (0-22) LNs, p<0.01). In addition, SPECT/CT led to a high spatial resolution and anatomical localization of SLNs. Thus, SPECT/CT identified aberrant lymphatic drainage in 7/40 (17.5%) patients. There were no significant differences, but significant correlation was found between SPECT/CT and intraoperative SLN identification. Regarding inguino-femoral LNs, for all patients who underwent complete groin dissection, sensitivity was 100%, NPV was 100% and false negative rate was 0%. CONCLUSION: SPECT/CT leads to higher SLN identification compared to LSG in vulvar cancer. Due to its higher spatial resolution and three-dimensional anatomical localisation of SLNs, SPECT/CT provides the surgeon with important additional information, facilitates intraoperative SLN detection and predicts aberrant lymphatic drainage.

Age-dependent differences in borderline ovarian tumours (BOT) regarding clinical characteristics and outcome: results from a sub-analysis of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) ROBOT study.

BACKGROUND: Approximately one-third of all borderline ovarian tumours (BOT) are diagnosed in patients with child-bearing potential. Detailed information regarding their specific characteristics and prognostic factors is limited. METHODS: Clinical parameters of BOT patients treated between 1998 and 2008 in 24 German centres were retrospectively investigated. Central pathology review and prospective follow-up were carried out. Patients <40 versus ≥40 years were analysed separately and then compared regarding clinico-pathological variables and prognosis. RESULTS: A total of 950 BOT patients with a median age of 49.1 (14.1-91.5) years were analysed [280 patients <40 years (29.5%), 670 patients ≥40 years (70.5%)]. Fertility-preserving surgery was carried out in 53.2% (149 of 280) of patients <40 years with preservation of the primarily affected ovary in 32 of these 149 cases (21.5%). Recurrence was significantly more frequent in patients <40 years (19.0% versus 10.1% 5-year recurrence rate, P < 0.001), usually in ovarian tissue, whereas disease-specific overall survival did not differ between the subgroups. In case of recurrent disease, malignant transformation was less frequent in younger than in older patients (12.0% versus 66.7%, P < 0.001), mostly presenting as invasive peritoneal carcinomatosis. Multivariate analysis for patients <40 years identified advanced International Federation of Gynecology and Obstetrics (FIGO) stage and fertility-sparing approach as independent prognostic factors negatively affecting progression-free survival (PFS) while, for patients ≥40 years, higher FIGO stage and incomplete staging was associated with impaired PFS. CONCLUSIONS: Despite favourable survival, young BOT patients with child-bearing potential are at higher risk for disease recurrence. However, relapses usually remain BOT in the preserved ovaries as opposed to older patients being at higher risk for malignant transformation in peritoneal or distant localisation. Therefore, fertility-sparing approach can be justified for younger patients after thorough consultation.

Isthmocervical labelling and SPECT/CT for optimized sentinel detection in endometrial cancer: technique, experience and results.

OBJECTIVE: We evaluated the clinical feasibility of a new injection technique for sentinel detection in endometrial carcinoma (EC), transcervical subepithelial injection into the isthmocervical region of the myometrium. We compared detection of sentinel lymph nodes (SLN) by single photon emission computed tomography with CT (SPECT/CT) with planar lymphoscintigraphy. METHODS: This is a unicentric prospective study. In all patients, transcervical injection of 10 MBq Technetium-99m-nanocolloid was performed into the isthmocervical myometrium without anaesthesia. After 40 (30-60) min, lymphoscintigraphy and SPECT/CT were performed. Patent blue was administered before surgery. The number and localisation of SLN detected in SPECT/CT and lymphoscintigraphy were recorded and compared to the SLN and non-SLN dissected intra-operatively. RESULTS: Between August 2008 and March 2012, 31 patients with EC were enrolled. The new transcervical injection of labelling substances led to high intra-operative (90.3%) detection rates, pelvic bilateral (57%), para-aortic (25%). SPECT/CT significantly identified more SLN than lymphoscintigraphy (mean 2.2 (1-8) to 1.3 (1-7)) in more patients (29/31 (93.5%) to 21/31 (68%), p<0.01). If SLN were identified in one hemi-pelvis, the histological evaluation of the SLN correctly predicted lymph node (LN) metastases for this basin which led to sensitivity 100%, negative predictive value (NPV) 100%, and false negative results 0%. CONCLUSION: Transcervical SLN marking in combination with SPECT/CT is easily applicable and leads to high physiologic detection rates in pelvic and para-aortic lymphatic drainage areas. Non-affected SLN truly predicted a non-affected LN basin. Combining both methods SLN dissection may be a safe and feasible staging technique for clinical routine in EC.

The biology of malignant breast tumors has an impact on the presentation in ultrasound: an analysis of 315 cases.

BACKGROUND: The aim of this study was to evaluate the relation of some ultrasound morphological parameters to biological characteristics in breast carcinoma. METHODS: Ultrasound data from 315 breast masses were collected. We analyzed the ultrasound features of the tumors according to the ACR BI-RADS®-US classification system stratified by hormone receptor status, HER2 status, histology grade, tumor type (ductal versus lobular), triple-negativity, breast density, tumor size, lymph node involvement and patient's age. RESULTS: We found a variety of ultrasound features that varied between the groups. Invasive lobular tumors were more likely to have an angulated margin (39% versus 22%, p = 0.040) and less likely to show posterior acoustic enhancement (3% versus 16%, p = 0.023) compared to invasive ductal carcinoma. G3 tumors were linked to a higher chance of posterior acoustic enhancement and less shadowing and the margin of G3 tumors was more often described as lobulated or microlobulated compared to G1/G2 tumors (67% versus 46%, p = 0.001). Tumors with an over-expression of HER2 exhibited a higher rate of architectural distortions in the surrounding tissue, but there were no differences regarding the other features. Hormone receptor negative tumors were more likely to exhibit a lobulated or microlobulated margin (67% versus 50%, p = 0.037) and less likely to have an echogenic halo (39% versus 64%, p = 0.001). Furthermore, the posterior acoustic feature was more often described as enhancement (33% versus 13%, p = 0.001) and less often as shadowing (20% versus 47%, p < 0.001) compared to hormone receptor positive tumors. CONCLUSION: Depending on their biological and clinical profile, breast cancers are more or less likely to exhibit the typical criteria for malignancy in ultrasound. Moreover, certain types of breast cancer tend to possess criteria that are usually associated with benign masses. False-negative diagnosis may result in serious consequences for the patient. For the sonographer it is essential to be well aware of potential variations in the ultrasound morphology of breast tumors, as described in this paper.

Analysis of the impact of PAPP-A, free ß-hCG and nuchal translucency thickness on the advanced first trimester screening.

OBJECTIVES: The intention of this study is to analyze the impact of the single parameters NT, PAPP-A and free ß-hCG used in combined first trimester screening and to determine their contribution in the risk assessment. METHODS: A retrospective risk assessment on the advanced first trimester screening (AFS) algorithm was made to determine the effect of a particular parameter while the remaining ones were fixed for calculation. Afterward data were recalculated by the AFS module. Test performance was measured by receiver operating characteristics (ROC) curves and their area under curve (AUC). RESULTS: Among the 14,862 cases are 14,748 healthy fetuses, 86 with trisomy 21, 22 with trisomy 18 and 6 with trisomy 13. Some settings obtain at default cut-off a very high sensitivity. However, a lack of specificity, as a high false-positive rate, too. The ROC analysis was best for NT, followed by PAPP-A. Free ß-hCG showed the lowest AUC. Combining PAPP-A and free ß-hCG offered a better AUC than each parameter alone. Best test performance was obtained by including all three parameters. DISCUSSION: A detection rate of 69 % for testing NT discretely is in order with present study data. PAPP-A is following and free ß-hCG is not useful with a test positive rate of about a third. The detection rate of the biochemical parameters combined is higher than for NT alone, but results in a five times higher punctuation rate. All parameters together in the AFS provide the best test performance. The impact of each parameter NT, PAPP-A and free-ß-hCG in a combined test strategy is nearly a third. Thus, every single parameter is needed to provide a high detection rate for all of the trisomies and minimize the number of unnecessary invasive diagnostics.

A phase II trial (AGO 2.11) in platinum-resistant ovarian cancer: a randomized multicenter trial with sunitinib (SU11248) to evaluate dosage, schedule, tolerability, toxicity and effectiveness of a multitargeted receptor tyrosine kinase inhibitor monotherapy.

BACKGROUND: Recurrent platinum-resistant ovarian cancer usually has a poor outcome with conventional chemotherapeutic therapy and new treatment modalities are warranted. This phase II study was conducted to evaluate sunitinib, an oral antiangiogenic multitargeted tyrosin kinase inhibitor, in this setting. MATERIAL AND METHODS: The primary end point of this randomized phase II trial was the objective response rate according to RECIST criteria and/or Gynecologic Cancer InterGroup CA125 response criteria to sunitinib in patients with recurrent platinum-resistant ovarian cancer who were pretreated with up to three chemotherapies. A selection design was employed to compare two schedules of sunitinib (arm 1: 50 mg sunitinib daily orally for 28 days followed by 14 days off drug; and arm 2: 37.5 mg sunitinib administered daily continuously). RESULTS: Of 73 patients enrolled, 36 patients were randomly allocated to the noncontinuous treatment arm (arm 1) and 37 patients were randomly allocated to the continuous treatment arm (arm 2). The mean age was 58.8 and 58.5 years, respectively. We observed six responders (complete response + partial response) in arm 1 (16.7%) and 2 responders in arm 2 (5.4%). The median progression-free survival (arm 1: 4.8 [2.9-8.1] months; arm 2: 2.9 [2.9-5.1] months) and the median overall survival (arm 1: 13.6 [7.0-23.2] months; arm 2: 13.7 [8.4-25.6] months) revealed no significant difference. Adverse events included fatigue as well as cardiovascular, gastrointestinal and abdominal symptoms, hematologic and hepatic laboratory abnormalities. Pattern and frequency of adverse events revealed no substantial differences between both treatment groups. CONCLUSIONS: Sunitinib treatment is feasible and moderately active in relapsed platinum-resistant ovarian cancer. The noncontinuous treatment schedule should be chosen for further studies in ovarian cancer.

Characterisation of the learning curve of caesarean section.

INTRODUCTION: Caesarean section is one of the common operations in medicine. As almost all interventions, the quality of the operation depends on the training and skills of the surgeon. This study aims at characterising the learning curve of caesarean section. MATERIAL AND METHODS: All patients with a singleton pregnancy who underwent a caesarean section between 2000 and 2009 in our university hospital were identified. We analysed datasets from beginners (no experience at all) and experienced surgeons (>300 caesarean sections, consultant) comparing the parameter incision-suture time (I-S time), incision-delivery time (I-D time), maternal blood loss, umbilical artery pH (ua-pH), APGAR score after 1, 5 and 10 min, mean time in hospital and postoperative complications. In addition, the first 100 caesarean sections of each beginner surgeon were divided in groups of 10 (1-10, 11-20, etc.) and analysed using the above-mentioned parameters. The learning curves were calculated. RESULTS: 2,515 of 3,844 operations were carried out by 23 experienced surgeons versus 1,329 operations by 22 beginners. The I-S time and I-D time was significantly higher in the beginners group than in the experienced surgeon's group (45.9 vs. 41.3 min, p < 0.001). Furthermore, for the first ten caesarean sections, the mean I-S time (47.9 min, 95% CI 45.7-50.0 min vs. 31-40th caesarean section with 43.1 min, 95% CI 40.9-45.3 min, p < 0.0001) and I-D time (9.5 min, 95% CI 8.6-10.5 min vs. 71-80th caesarean section with 4.8 min, 95% CI 4.2-5.4 min, p < 0.0001) was significantly higher than of the subsequent datasets of ten operations, showing a typical learning curve. CONCLUSION: The learning curve for the total operation time and incision-delivery time reaches a flatter part after 10-15 caesarean sections. However, the learning process is highly individualised and difficult to predict, so that supervision and evaluation of the trainee by an experienced surgeon is important.

[Intraoperative pathological rapid investigations in breast surgery]. / Intraoperative pathologische Sofortuntersuchung in der Mammachirurgie.

In breast surgery intraoperative frozen sections for the diagnosis of malignancy has lost impact and has largely been replaced by preoperative core needle biopsies. Nevertheless, there is still need for immediate pathological investigation of native breast tissue during surgery due to three reasons: (1) macroscopic and microscopic evaluation of resection margins, (2) the histological analysis of sentinel lymph nodes in order to circumvent secondary axillary surgery and (3) the preparation of native tissue for tumor banking or measurement of biomarkers. Because histology provides only a facultative component of immediate pathological examination of breast specimens during surgery, the term frozen section does not seem to be appropriate anymore. Intraoperative evaluation of resection specimens by pathologists provides surgically relevant information immediately, guarantees standardized preparation and fixation of specimens and enables tissue banking of native tissue for assessment of biological markers.

Evaluation of variation in the phosphoinositide-3-kinase catalytic subunit alpha oncogene and breast cancer risk.

BACKGROUND: Somatic mutations in phosphoinositide-3-kinase catalytic subunit alpha (PIK3CA) are frequent in breast tumours and have been associated with oestrogen receptor (ER) expression, human epidermal growth factor receptor-2 overexpression, lymph node metastasis and poor survival. The goal of this study was to evaluate the association between inherited variation in this oncogene and risk of breast cancer. METHODS: A single-nucleotide polymorphism from the PIK3CA locus that was associated with breast cancer in a study of Caucasian breast cancer cases and controls from the Mayo Clinic (MCBCS) was genotyped in 5436 cases and 5280 controls from the Cancer Genetic Markers of Susceptibility (CGEMS) study and in 30 949 cases and 29 788 controls from the Breast Cancer Association Consortium (BCAC). RESULTS: Rs1607237 was significantly associated with a decreased risk of breast cancer in MCBCS, CGEMS and all studies of white Europeans combined (odds ratio (OR)=0.97, 95% confidence interval (CI) 0.95-0.99, P=4.6 × 10(-3)), but did not reach significance in the BCAC replication study alone (OR=0.98, 95% CI 0.96-1.01, P=0.139). CONCLUSION: Common germline variation in PIK3CA does not have a strong influence on the risk of breast cancer.