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Wir berichten uber eine 23jahrige Patientin mit persistierendem Ductus omphaloentericus. Die Diagnose wurde histologisch gesichert. Weitere Differentialdiagnosen einer Blutung aus dem Naraornnd sind die Urachusfistel und die Endometriose.

Introduction.: For routine staging of patients with primary breast cancer, clinical practice guidelines of many medical societies recommend chest X-ray, liver ultrasound and bone scan. With respect to expanding health care costs and patients' psychological distress it has been supposed, that there might be a group of breast cancer patients, who do not need these imaging studies. Methods.: Four hundred and eighty-eight consecutive patients with primary breast cancer who had primary surgery at our institution and complete work-up for distant metastases including chest X-ray, liver ultrasound, and bone scan were studied. Results.: We found distant metastases at the time of primary diagnosis in 19 patients (3.9%). Bone metastases were found in 2.7%, liver metastases in 1.0%, and pulmonary metastases in 0.4%. However, in breast tumors smaller than 1cm, no metastatic lesions were found, whereas 18.2% of the patients with pT4 tumors had metastases. In 2.4% of screening imaging studies, metastases were ruled out by additional imaging. Conclusion.: Based on our data and a review of the literature, we suggest that chest X-ray, liver ultrasound and bone scan can be omitted in the staging of asymptomatic patients with pT1a or pT1b disease

DNA-dependent protein kinase (DNA-PK) is involved in non-homologous end joining which repairs DNA double-strand breaks introduced by irradiation and radiomimetic agents. DNA-PK interacts with p53 but may also have p53-independent functions. The present study investigated whether disruption of the gene for the catalytic subunit DNA-PKcs affects chemosensitivity in p53-deficient cells. Drug sensitivity of DNA-PKcs +/+ /p53 +/+ , DNA-PKcs +/+ /p53 -/- , DNA-PKcs -/- ps3 +/+ , and DNA-PKcs -/- /p53 -/- mouse lung-fibroblasts was determined by the MTT assay, the clonogenic assay, and trypan blue exclusion. Susceptibility to apoptosis was determined by DNA fragmentation (TUNEL) and by caspase-3 cleavage. We show that p53-deficient cells were 2 to 3-fold resistant to treatment with doxorubicin, epirubicin, cisplatin, and docetaxel as compared to wild-type cells. We further demonstrate that the additional loss of DNA-PKcs function in p53-deficient cells resulted in a 2-fold increase in sensitivity to doxorubicin and epirubicin as documented by the MTT assay, clonogenic assay, and trypan blue exclusion. Doxorubicin-induced hypersensitivity in these cells correlated with a transient G 2 /M checkpoint activation but did not seem to correlate with apoptosis. The data indicate that additional loss of DNA-PKcs in p53-deficient cells reverses anthracycline-resistance imposed by p53-deficiency, and that DNA-PKcs modulates p53-independent pathways responding to DNA damage induced by anthracyclines. They also indicate that processes other than apoptosis may contribute to the increased cytotoxicity to anthracyclines. DNA-PKcs may thus be a potential target for functional inhibition, which might increase the efficacy of some anti-tumour agents in the treatment of cancers mutated in the p53 gene.

The aim of this study was to assess nodal enhancement with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) during preoperative staging of gynecological pelvic tumors within the same imaging session for the primary tumor. Pelvic MRI was performed 18-28 h after intravenous infusion of USPIO (Combidex/Sinerem, 2.6 mg Fe/kg body weight) in 13 women (mean age 51 years) scheduled for surgery for biopsy proven ( n=11) or clinically suspected ( n=2) uterine carcinoma. Axial T1-weighted spin-echo (SE), T2-weighted fast SE (FSE; with fat saturation), fast spoiled gradient-recalled (FSPGR) echo, sagittal and oblique T2-weighted FSE sequences were acquired on a 1.5-T system. Lymph nodes were prospectively staged using standard criteria, i.e., size and shape, as well as USPIO enhancement. Results were correlated with histology findings. MRI correctly staged all primary uterine tumors. In one case, the preoperative diagnosis of stage IV switched the therapeutic approach to radiochemotherapy. Ninety-one (86 benign, 5 malignant) of the histologically characterized nodes could be correlated with their MRI counterparts. One node was false positive; three micrometastases greater than 5 mm and one 5-mm metastasis were missed. On a nodal basis, the sensitivity score was 0.33 and the specificity score, 0.99. On a patient basis, the sensitivity score was 0.25 and the specificity score, 0.80. Our preliminary results indicate that USPIO-enhanced pelvic MRI for preoperative nodal assessment is feasible within one imaging session for primary tumors and that it has a high specificity. However, the low sensitivity in the present study is a limitation for the clinical application of this technique.

Background Previous studies defining perioperative risk factors for allogeneic transfusion requirements in cardiac surgery were limited to highly selected cardiac surgery populations or were associated with high transfusion rates. The purpose of this study was to determine perioperative risk factors and create a formula to predict transfusion requirements for major cardiac surgical procedures in a center that practices a multimodality approach to blood conservation. Methods We performed an observational study on 307 consecutive patients undergoing coronary artery bypass grafting, valve, and combined (coronary artery bypass grafting and valve) procedures. An equation was derived to estimate the risk of transfusion based on preoperative risk factors using multivariate analysis. In patients with a calculated probability of transfusion of at least 5%, intraoperative predictors of transfusion were identified by multivariate analysis. Results Thirty-five patients (11%) required intraoperative or postoperative allogeneic transfusions. Preoperative factors as independent predictors for transfusions included red blood cell mass, type of operation, urgency of operation, number of diseased vessels, serum creatinine of at least 1.3 mg/dL, and preoperative prothrombin time. Intraoperative factors included cardiopulmonary bypass time, three or fewer bypass grafts, lesser volume of acute normovolemic hemodilution removed, and total crystalloid infusion of at least 2,500 mL. The derived formula was applied to a validation cohort of 246 patients, and the observed transfusion rates conformed well to the predicted risks. Conclusions A multimodality approach to blood conservation in cardiac surgery resulted in a low transfusion rate. Identifying patients' risks for transfusion should alter patient management perioperatively to decrease their transfusion rate and make more efficient use of blood resources.

BRCA1 is implicated in cellular responses to DNA damage, thereby substantially contributing to maintenance of the genome integrity. Mutations in the BRCA1 gene occur in breast and ovarian cancer and mutations that disable p53 are frequently found in human cancers, often accompanied by mutations in additional genes, contributing to tumor progression or high-grade malignancy. Therefore, the role of BRCA1 in the sensitivity to anticancer agents in p53-deficient cells was investigated using p53-deficient mouse knockout cell lines either deficient or proficient in Brca1 function. We report that Brca1-deficiency in p53-null cells was associated with increased sensitivity to the topoisomerase I poisons camptothecin and topotecan, the topoisomerase II poisons doxorubicin, mitoxantrone and etoposide, and to the platinum compounds carboplatin and oxaliplatin, but not to the antimetabolites 5-fluorouracil and gemcitabine and the taxanes docetaxel and paclitaxel. The increased growth inhibition to doxorubicin after loss of Brca1 correlated with increased cell killing caused by increased apoptosis. The data presented here indicate that Brca1 modulates p53-independent DNA damage response pathways and they support the case of a role of Brca1 to protect cells from apoptosis-mediated cell death in p53-deficient cells. These results suggest a higher chemotherapy susceptibility of cells disabled in both functions and they foster the concept that functional inhibition of BRCA1 may be a valuable adjunct to anticancer agents to increase the efficacy of chemotherapy in the treatment of p53-mutated cancers.

Background: Aortic valve replacement (AVR) in the presence of a calcified aorta or patent grafts may preclude clamping of the ascending aorta. We employed deep hypothermic circulatory arrest in order to circumvent this problem. Methods: Between January 1993 and December 2000, 415 patients underwent AVR in our department. Eight of these were operated using deep hypothermic circulatory arrest. There were 5 males, and mean age was 72 years (range 56–81). Indications for using circulatory arrest were reoperation with patent grafts and/or severe calcification of the ascending aorta. In six patients, cardiopulmonary bypass was achieved via femoro-femoral bypass, and in two via aortic-right atrial cannulation. Retrograde cerebral perfusion was employed in five. Mean bypass time was 155 minutes (range 122–187), and mean circulatory arrest time was 38 minutes (range 31–49). Results: There was no operative mortality, and no patient suffered any neurologic sequelae. Echocardiography showed all valves to be functioning well. Conclusions: AVR under deep hypothermic circulatory arrest can be accomplished with an acceptable degree of safety. It should be considered as an alternative in patients in whom aortic clamping is prohibitive, and might otherwise be considered inoperable. The ability to connect the patient to bypass and the presence of a “window” to allow aortotomy are prerequisites for employing this method.

Background The use of prosthetic material (rather than a homograft) for ascending aorta/aortic valve replacement (Bentall procedure) in cases of acute prosthetic valve endocarditis is controversial. We report favorable results using this technique almost exclusively (a homograft was used in only 3 patients with hematological problems) during a 12-year interval. Methods Twenty-eight patients (55 ± 14 years; 22 male) underwent a Bentall procedure for acute prosthetic valve endocarditis between 1988 and 2000. Twenty-five patients had undergone previous aortic valve replacement (1 with concomitant mitral valve replacement, 4 with coronary artery bypass grafting), and 3 had had a previous Bentall operation. The median interval between initial surgery and reoperation was 13 months (range, 1 to 106). Sixty-eight percent of operations were urgent or emergencies. Ninety-three percent of patients had significant aortic regurgitation; complete annuloaortic dehiscence occurred in 71%, and in 57%, an abscess was found. Causative organisms were identified in 25 of 28 patients: Staphylococcus epidermidis (9), Staphylococcus aureus (7), Streptococcus viridans (6), Pseudomonas (2), and Legionella (1). Results Twenty-three patients had mechanical and 5 had biological valves implanted during the Bentall procedure. Hypothermic circulatory arrest was used in 64%. Hospital mortality was 11%: there was one intraoperative death, and two before discharge (one cardiac, one sepsis). Eighty-nine percent survived without stroke. During follow-up (median, 44.5 months; complete in 92%), 1 patient died of recurrent endocarditis at 4 months. Conclusions These results indicate that prosthetic root replacement may be superior to use of a homograft for acute aortic prosthetic valve endocarditis, with only a 4% incidence of recurrent endocarditis and reoperation.

To evaluate magnetic resonance (MR) imaging with ultrasmall superparamagnetic iron oxide (USPIO) enhancement for preoperative axillary lymph node staging in patients with breast cancer by using histopathologic findings as the standard of reference.MR imaging was performed with a 1.5-T system within 24-36 hours after the start of intravenous slow-drip infusion of USPIO in 20 patients with breast cancer who were scheduled for surgery, followed by gadolinium-enhanced MR imaging. Lymph nodes were staged prospectively by using newly established criteria, and results were correlated with histologic findings.In two patients, preoperative findings led to a change in therapeutic approach, and neoadjuvant chemotherapy was given; both patients were excluded from statistical analysis. Results of axillary staging with USPIO-enhanced MR imaging were true-positive in nine, true-negative in seven, false-positive in zero, and false-negative in two of 18 patients (sensitivity, 82%; specificity, 100%; positive predictive value, 100%; second reader, kappa = 1.0). Four hundred five lymph nodes were detected with MR imaging. For first and second readers, respectively, lymph node-based sensitivity was 83% and 73% and specificity was 96% and 97% (kappa = 0.68). USPIO as the intravascular contrast agent could not replace gadolinium for assessment of the primary tumor; however, no clinically relevant interaction was seen. Thus, an integrated imaging approach was feasible in all patients.USPIO-enhanced MR imaging has the potential to become an adjunct to conventional MR imaging of the breast for preoperative assessment of axillary lymph nodes in patients with breast cancer.

BACKGROUND AND OBJECTIVES To determine the feasibility of photodynamic therapy (PDT) of vulvar and vaginal condyloma and intraepithelial neoplasia (VIN, VAIN) and to compare PDT results with conventional treatments. STUDY DESIGN/MATERIALS AND METHODS Thirty-eight patients with vulvar or vaginal intraepithelial neoplasia (VIN) grade II/III (n = 22) or condyloma (n = 16) had 10% 5-aminolevulinic acid (ALA)-gel applied topically. After 2-4 hours, 80-125 J/cm(2) laser light at a wavelength of 635 nm was applied. PDT was compared to conventional treatments for condyloma (CO(2) laser evaporation) and for VIN III (laser evaporation, surgical excision). RESULTS The complete clearance rate for condyloma treated by PDT was 66% and the rate for IN was 57% (as determined by biopsy). Of the neoplasia patients, none with hyperkeratotic VIN (n = 4) responded, and only one of four with increased pigmentation cleared. No scarring occurred, and postoperative discomfort lasted 4.9 +/- 3.4 days. Reduced disease-free survival (DFS) was associated with multifocal VIN (P = 0.02, OR 2.17, 95% CI 1.15-4.08), but DFS did not vary with treatment mode. CONCLUSIONS Although PDT is not equally efficacious for all subgroups, PDT for condyloma and intraepithelial neoplasia appears to be as effective as conventional treatments, but with shorter healing time and excellent cosmetic results.

This contribution, based on a statistical approach, undertakes to link data on resources (personnel and financial means) and the working of the administration of penal justice (prosecution, sentencing) taking into account the nationality of those prosecuted. In order to be able to distinguish prosecution and sentencing practices of judicial authorities and possible processes of discrimination, diverse sources have been used such as data from court administrations, public finances and police forces, collected by the Swiss Federal Statistical Office and the Swiss Federal administration of finances. The authors discuss discrimination in prosecution and sentencing between Swiss residents and foreigners taking into account localization and resources regarding personnel and public finances.

In gynecological oncology, patients particularly with early-stage endometrial or cervical carcinomas can benefit from minimally invasive procedures. In cases of cervical carcinoma, laparoscopic lymphonodectomy can help identify patients who should first undergo chemoradiotherapy. In cases of advanced ovarian carcinoma, laparoscopy is only a diagnostic option and not a therapy of its own. The use of robot-assisted laparoscopy (DaVinci) in gynecological oncology is currently evaluated.

To investigate the differential diagnostic capacity of the frequency-volume chart in 132 women with urinary incontinence.For each patient, the readings of two 24-h frequency-volume charts were compared to the urodynamic diagnosis which was used as the gold standard in 73 genuine stress incontinent women, in 23 urge incontinent women, and in 36 women with mixed incontinence.The total voided volume, the mean voided volume, the largest single voided volume, and the smallest single voided volume were statistically differentiating single parameters among the three groups (p0.05). Applying logistic regression to the two well-defined groups of patients, the one with urge incontinence and the one with genuine stress incontinence, the frequency of micturition during nighttime revealed the best discriminatory power for these conditions.This study shows that in the frequency-volume chart micturition during nighttime discriminates best between urge and stress incontinence.

Das Konzept des Mammakarzinoms hat sich in den letzten Jahrzehnten von einer lokalen Erkrankung immer mehr Richtung systemisches Leiden verschoben. Heute kann die Radikalitat der Operation durch brusterhaltende Verfahren und durch die Sentinellymphonodektomie minimiert werden. Durch den Einsatz von zytostatischen und endokrinen Systemtherapien konnte gleichzeitig ein wesentlicher Gesamtuberlebensvorteil erreicht werden. Hochrisikosituationen konnen definiert und entsprechend mit adjuvanten Systemtherapien behandelt werden. Aktuelle Ansatze umfassen den sequentiellen oder simultanen Einsatz von Anthrazyklinen und Taxanen, die Kombination mit Antimetaboliten, Antikorpern und Tyrosinkinaseinhibitoren sowie dosisdichte Chemotherapien. In der adjuvanten Therapie des Mammakarzinoms bei der postmenopausalen rezeptorpositiven Patientin ist Tamoxifen nicht mehr alleiniger Standard. Ein Aromatasehemmer sollte in jedem Fall zum Einsatz kommen. = In the last few decades, the notion of breast cancer has developed from a local disease rather to a systemic illness. Today radical operations can mostly be avoided by breast-conserving techniques and sentinel lymph node dissection. By the use of cytostatic and endocrine systemic therapies, an essential gain in overall survival could be obtained, too. High-risk situations can be determined and dealt with accordingly by adequate systemic therapies. Current approaches include the sequential or simultaneous use of anthracyclines and taxanes, the combination with antimetabolites, antibodies and tyrosine kinase inhibitors as well as dose-dense chemotherapeutic regimens. In the adjuvant treatment of breast cancer of postmenopausal receptor-positive patients, tamoxifen is not the gold standard anymore. An aromatase inhibitor should be used at any rate.

Hypertensive diseases in pregnancy are one of the main reasons of maternal, fetal and neonatal morbidity and mortality. As preeclampsia is a multisystem disorder with different clinical characteristics, prevention, diagnosis and therapy of this disease require a close interdisciplinary cooperation. The present papers will summarize the status quo of the management of preeclampsia.

Zusammenfassung: In den letzten Jahren hat sich die Urogynakologie zu einer sehr innovativen gynakologischen Subspezialitat entwickelt. Neue Erkenntnisse haben zu einer Vielzahl neuer medikamentoser und operativer Therapiemoglichkeiten gefuhrt. Mittels Schlingenoperationen kann in uber 80% der Patientinnen mit einer Belastungsinkontinenz eine Besserung erzielt werden. Ebenso stehen seit kurzer Zeit Medikamente zur Therapie der Belastungsinkontinenz zur Verfugung. Injektionen von Botulinumtoxin A in den Detrusormuskel stellen bei therapieresistenter uberaktiver Blase eine Erfolg versprechende Behandlungsstrategie dar.

Selection of cells for resistance to cisplatin results in resistance to arsenite and selenite. Mammalian cells detoxify arsenite and selenite by S-adenosylmethionine dependent methylation. We aimed to investigate whether S-adenosylmethionine dependent methylation is involved in the cellular metabolism of cisplatin. Treatment of human ovarian cancer cells 2008 and the cisplatin-resistant subline 2008/C13*5.25 with the S-adenosylhomocysteine hydrolase inhibitor adenosine-dialdehyde, an indirect inhibitor of transmethylation, resulted in a significant elevation (16-fold in 2008, 6-fold in 2008/C13*5.25) in the cellular content of S-adenosylhomocysteine without changing S-adenosylmethionine. Adenosine dialdehyde synergistically enhanced the cytotoxicity of cisplatin and carboplatin as evidenced by combination indices

The treatment of breast cancer is changing continually. Thus, sentinel lymph node dissection is considered today as standard in the therapy of small unifocal breast carcinoma with clinically negative axillary lymph nodes. Concerning adjuvant therapy, the 9th Early Adjuvant Breast Cancer Meeting, along with a consensus conference, took place in Saint Gall on January 26-29, 2005. The publication of the corresponding congress report is expected for early summer of 2005.

Die Einführung der Sonographie hat in der Geburtshilfe zu enormem Fortschritt geführt, doch durch diese Erfolge haben viele Schwangere nun Erwartungen, die nicht immer erfüllt werden können. Pränatal nicht erkannte Fehlbildungen ziehen daher immer häufiger Regressansprüche nach sich. Durch Qualitätssicherung und rechtsverbindliche Aus- und Weiterbildung auf europäischer Ebene könnte die Ärzteschaft dieser Entwicklung aktiv entgegenwirken.

The continuing increase in teenage pregnancies and abortions calls for more effective sex education on the one hand, including a detailed explication of the (perfectly normal) changes an adolescent body is undergoing, but we also need to understand the way teenagers actually do use contraceptives. Modern contraception for teenagers should not cause any side effects and its efficacy must not be linked to compliance. Gynaecologists must acquaint themselves with the laws covering the prescription of contraceptives to adolescents. Whether hormonal contraceptives for men are also suitable for teenage boys remains to be seen. Advising mentally or physically handicapped teen-agers or those with chronic diseases on their contraceptive options is particularly challenging. Adolescents are more prone to contract HPV infections and thus need to be screened, counselled and told about the association between HPV and cervical dysplasia.

Background Oocyte in vitro maturation (IVM) and cryopreservation at the time of routine ovarian tissue freezing may be offered to cancer patients as an additional option for fertility preservation. This study aimed to investigate the developmental capacity of oocytes isolated from unstimulated ovaries. Methods Immature oocytes (n = 63) from seven consenting premenopausal patients were analysed. Oocytes were collected during routine laparoscopic examination with biopsy of an ovary (cystic adnexal mass, n = 3; cervical adenocarcinoma, n = 2) or oophorectomy (sex reassignment surgery, n = 2) without previous stimulation of the ovaries. The stage of the patient’s menstrual cycle was not considered. Oocytes in all visible antral follicles were aspirated from ovaries, cultured in IVM medium and vitrified at the MII stage before being kept in liquid nitrogen for at least one month. After warming, oocytes were subjected to parthenogenetic activation by chemical stimulus. Their further development was recorded at intervals of 24 hours for up to 6 days of culture. Results 61.9% of oocytes matured in vitro within 48 hours. The survival rate after vitrification and warming was 61.5%. A total of 75% of surviving oocytes were able to respond to artificial activation, 44.4% of the parthenotes developed to early embryonic stage. However, only 1 in 18 (5.6%) of the resulting embryos reached blastocyst stage. Conclusions Oocytes matured in vitro from unstimulated ovaries seem to have limited developmental potential after cryopreservation and artificial activation. Although the outcome of IVM for non-stimulated oocytes is poor, it is currently the only chance besides cryopreservation of ovarian tissue for women for whom ovarian stimulation is not possible due to life circumstances. Based on our preliminary results, we suggest that the use of cryopreserved ovaries for fertility preservation in women with cancer warrants further investigation.

A 32-year-old woman, in the 22nd week of pregnancy, underwent emergency coronary artery bypass grafting to the left anterior descending artery (LAD). She had suffered an acute myocardial infarction 10 days previously, and continued to suffer from intractable angina pectoris afterwards. Cardiac catheterization revealed spontaneous dissection of the LAD. The left internal mammary artery was used to bypass the LAD, and the operation was performed on a beating heart without the use of cardiopulmonary bypass. The patient's recovery was uneventful, and ultrasound examination and pulse monitoring of the fetus were both normal. She subsequently gave birth to a healthy term baby. To our knowledge this is the second report of coronary artery bypass surgery performed successfully in a pregnant woman. We believe the unique surgical approach avoided the risk of cardiopulmonary bypass to the fetus and placenta.

The comparison of the operations of the administration of justice among cantons shows on one side large differences in the three major types of sentencing, in the use of pre-trial detention and the unsuspended prison sanction. When combined, one finds however very weak relationships when considering absolute, percentage or weighted results. On the other side, the outcome of these different policies is much paradoxical as there are no differences when comparing recidivism rates among cantons, despite strong differences in the use of pre-trial detention and the sentencing with prison sanctions. The paradoxical outcome of crime policies in terms of recidivism - e.g. the absence of differences of the outcome based on sanctions in the domain of less severe delinquency - suggests the need for more empirically informed crime policies. The role of justice administrators could be to participate in the dissemination of those findings as well as the dissemination of best practices among cantons with regard to outcomes and the use of resources - especially with consideration to the use of the prison sanction as it is the most costly and the most inefficient of all sanctions. Furthermore, the observance of the principle of equality before the law would be most likely be promoted.

In this paper we describe eBird, a citizen-science project that takes advantage of the human observational capacity to identify birds to species, which is then used to accurately represent patterns of bird occurrences across broad spatial and temporal extents. eBird employs artificial intelligence techniques such as machine learning to improve data quality by taking advantage of the synergies between human computation and mechanical computation. We call this a Human-Computer Learning Network, whose core is an active learning feedback loop between humans and machines that dramatically improves the quality of both, and thereby continually improves the effectiveness of the network as a whole. In this paper we explore how Human-Computer Learning Networks can leverage the contributions of a broad recruitment of human observers and processes their contributed data with Artificial Intelligence algorithms leading to a computational power that far exceeds the sum of the individual parts.

UNLABELLED The aim of this study was to find both predictors of axillary lymph node involvement and predictors of level II or III involvement. With these predictors patients should be selected who can be spared axillary lymph node dissection or who qualify for removal of only first-level lymph nodes. 239 consecutive patients with invasive breast cancer stage I-III treated with total axillary dissection were evaluated. In multiple logistic regression analysis 17 clinical and histopathological variables were included. We found 4 multivariate significant predictors for metastatic axillary involvement: Clinically positive axilla, peritumoural lymphatic vessel invasion, multicentric or multifocal tumours and a large number of past pregnancies. Multivariate significant predictors of involvement of level II or III were peritumoural lymphatic vessel invasion, younger age, larger tumour size, multicentric or multifocal tumours and postmenopausal patient. The metastatic involvement of more than 3 nodes was associated with young age and clinically positive axilla. With these easily available predictors a reliable assessment of risk of metastatic involvement of the upper levels of the axillary nodes could be defined. The binary logistic regression model to axillary node involvement had a rather unsatisfactory predictive value. CONCLUSIONS The risk calculation of level II or III involvement with these predictors may help the surgeon to find the adequate extent of axillary clearance needed in the individual patient. Multiparity proved to be an independent predictor of metastatic axillary node involvement.

Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium-specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II carcinoma subtypes. The PI3K-Akt-mTOR signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, immunohistochemical analyses of 521 human endometrial carcinomas identified frequent mTOR pathway activation in type I as well as type II endometrial carcinoma subtypes and mTOR pathway activation and p53 expression each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the PI3K-mTOR pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and PI3K-mTOR pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3293. doi:1538-7445.AM2012-3293

Introduction: Patients with advanced-stage serous cancers (ovarian, peritoneal and tubal) often develop ascites, a protein-rich fluid within the peritoneal cavity which causes significant morbidity and is associated with a poor prognosis. Aberrant glycosylation is a common feature of these cancers and this may impact on the humoral immune response. We hypothesized that serous cancer patients and healthy women have different profiles of anti-glycan antibodies in plasma and ascites. Method: Matched pairs of plasma and ascites were collected from 11 patients with advanced stage disease. A custom-made printed glycan array (PGA) allowed the simultaneous detection of anti-glycan antibodies (AGAs) to 203 chemically synthesised glycans, including some tumour-associated carbohydrate antigens. Identified candidate AGAs were additionally detected using a suspension array in an independent patient cohort of 230 patients. Candidates were selected by their discriminatory power between cancer and healthy controls. One top candidate was further analyzed for its biological behavior using ovarian cancer cell lines. Results: Using PGA, we detected a multitude of AGAs in both plasma and ascites. Levels of AGAs in serum and ascites correlated independent of ascites volume. Serous cancer patients had significantly different levels of plasma IgM to 31 glycans when compared to plasma of 14 healthy control patients, with IgM levels being lower in the cancer group. Significant differences in IgG plasma levels were found for 4 glycans. The trisaccharide P1, part of the P blood group system, was selected for further analyses. Plasma expression of P1 was found independent of cohort and method used. The human serous ovarian cancer cell line, IGROV1, was shown to express P1 and was subsequently sorted into P1-high, P1-low, and P1-negative subpopulations. We found that IGROV1/P1-expressing cells correlated with faster tumor cell migration and invasion. Treatment with a human anti-P1 IgM (clone P3NIL100) inhibited the proliferation of these tumour cells in vitro. Conclusion: P1 expression can be detected in ovarian cancer patients in independent of cohorts. P1 seems to be involved in cancer migration and invasion, and is therefore a potential target for ovarian cancer diagnosis and therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 517. doi:1538-7445.AM2012-517