High negative prediction for the Basel sarcoma score: Sonographic assessment of features suspicious of uterine sarcoma.

INTRODUCTION: In the management of uterine myomas, laparoscopic surgery with morcellation enables a minimal invasive procedure. Cases of unsuspected uterine sarcoma dissemination have been reported and led to regulative restrictions. To help to distinguish preoperatively myomas from sarcomas, we assessed the value of six sonographic criteria (Basel Sarcoma Score, BSS) in a prospective outpatient cohort of consecutive patients with uterine masses. MATERIAL AND METHODS: We prospectively evaluated all patients presenting with myoma-like masses planned for surgery with standardized ultrasound examination. BSS including the following criteria was investigated: rapid growth in past three months, high blood flow, atypical growth, irregular lining, central necrosis and oval solitary lesion. For each criterion, a score 0/1 was given. BSS (0-6) equals the sum of all given scores. Histological diagnosis was used as reference. RESULTS: Among 545 patients, 522 had the final diagnosis of myoma, 16 had peritoneal masses with sarcomatous components (PMSC), and seven had other malignancies. Median BSS for PMSC was 2.5 (range: 0-4) vs 0 for myomas (range: 0-3). The most common sonographic criteria leading to a false positive score in myomas were rapid growth in past three months and high blood flow. For the detection of sarcomatous masses with BSS threshold of >1, sensitivity was 93.8%, specificity 97.9%, and positive predictive value (PPV) and negative predictive value (NPV) were 57.7% and 99.8%, respectively (AUC 0.95). CONCLUSION: BSS can help distinguishing between myomas and sarcomatous masses, with high NPV. Caution is required when >1 criterion is present. As a simple tool, it could easily be integrated into routine myoma sonographic examination and help develop standardized assessment of uterine masses for better preoperative triage.

Application of a 21-Gene Recurrence Score in a Swiss Single-Center Breast Cancer Population: A Comparative Analysis of Treatment Administration before and after TAILORx.

In patients with hormone receptor positive, human epidermal receptor 2 negative (HR+/HER2-) negative breast cancer (BC), the TAILORx study showed the benefit of adding chemotherapy (CHT) to endocrine therapy (ET) in a subgroup of patients under 50 years with an intermediate Oncotype DX recurrence score (RS 11-25). The aim of the present study was to determine if the TAILORx findings, including the changes in the RS categories, impacted CHT use in the intermediate RS (11-25) group in daily practice, as well as to identify the main factors for CHT decisions. We conducted a retrospective study on 326 BC patients (59% node-negative), of which 165 had a BC diagnosis before TAILORx (Cohort A) and 161 after TAILORx publication (Cohort B). Changes in the RS categories led to shifts in patient population distribution, thereby leading to a 40% drop in the low RS (from 60% to 20%), which represented a doubling in the intermediate RS (from 30% to 60%) and an increase of 5% in the high RS (from 8-10% to 15%). The overall CHT recommendation and application did not differ significantly between cohort B when compared with A (19% vs. 22%, resp., p = 0.763). In the intermediate RS (11-25), CHT use decreased by 5%, while in the high-risk RS category (>25), there was an increase of 13%. The tumor board recommended CHT for 90% of the patients according to the new RS guidelines in cohort A and for 85% in cohort B. The decision for CHT recommendation was based on age (OR 0.93, 95% CI 0.08-0.97, p = 0.001), nodal stage (OR 4.77, 95% CI 2.03-11.22, p < 0.001), and RS categories (RS 11-25 vs. RS 0-10: OR 0.06 (95% CI 0.02-0.17), p < 0.001; RS > 26 vs. RS 11-25: OR 618.18 95% CI 91.64-4169.91, p < 0.001), but did not depend on the cohort. In conclusion, while the tumor board recommendation for CHT decreased in the intermediate RS category, there was an increase being reported in the high RS category, thus leading to overall minor changes in CHT application. As expected, among the younger women with intermediate RS and unfavorable histopathological factors, CHT use increased.

Antenatal predictors of stem cell content for successful umbilical cord blood donation.

PURPOSE: The most important HLA-independent factor for the selection of cord blood units (CBU) for hematopoietic stem cell transplantation is the total nucleated cell (TNC) count over 150 × 107 as a surrogate marker for stem cell content. The purpose of this prospective study was to define prenatal clinical predictors for TNC count that would help to identify successful CBU donors before the onset of active labor. METHODS: This was a prospective analysis of 594 CBUs, collected from all eligible term singleton pregnancies at Basel University Hospital between 4/2015 and 9/2016 analyzing several maternal and fetal factors. The impact of these factors on TNC count (< 150 × 107 cells vs. ≥ 150 × 107 cells) of the CBUs was modeled in a multivariate analysis. RESULTS: A total of 114 (19.2%) CBUs had a TNC count of ≥ 150 × 107. In a ROC analysis there was no significant difference between the AUC of all prenatal factors (AUC 0.62) and estimated fetal birth weight by ultrasound alone (AUC 0.62). For women planning a trial of labor a recruitment cut-off at an estimated birth weight of 3300 g would allow 72.6% of all donors with sufficient TNC count to be recruited and 22.8% of all collected CBUs would have a sufficient TNC count for banking. For women planning for elective CS a cut-off of 3400 g would allow 71.4% of all donors with sufficient TNC count to be recruited and 22.7% of all collected CBUs would have sufficient TNC count for banking. CONCLUSION: The estimated fetal birth weight within 2 weeks of delivery by ultrasound as single parameter can be considered at the time of recruitment to estimate the chances of a successful CBU donation.

High-grade serous peritoneal cancer follows a high stromal response signature and shows worse outcome than ovarian cancer.

In the era of personalized medicine, where transition from organ-based to individualized genetic diagnosis takes place, the tailoring of treatment in cancer becomes increasingly important. This is particularly true for high-grade, advanced FIGO stage serous adenocarcinomas of the ovary (OC), fallopian tube (TC), and peritoneum (PC), which are currently all treated identically. We analyzed three independent patient cohorts using histopathologically classified diagnosis and various molecular approaches (transcriptomics, immunohistochemistry, next-generation sequencing, fluorescent and chromogenic in situ hybridization). Using multivariate Cox regression model, we found that PC is more aggressive compared with advanced-stage OC independent of residual disease as shown by an earlier relapse-free survival in two large cohorts (HR: 2.63, CI: 1.59-4.37, P < 0.001, and HR: 1.66, CI: 1.04-2.63, P < 0.033). In line with these findings, transcriptomic data revealed differentially expressed gene signatures identifying PC as high stromal response tumors. The third independent cohort (n = 4054) showed a distinction between these cancer types for markers suggested to be predictive for chemotherapy drug response. Our findings add additional evidence that ovarian and peritoneal cancers are epidemiologically and molecularly distinct diseases. Moreover, our data also suggest consideration of the tumor-sampling site for future diagnosis and treatment decisions.

Should MMMT still be treated with adjuvant taxane-based combination chemotherapy?

BACKGROUND: Malignant mixed Mullerian tumors of endometrial (MMMT-E) and ovarian (MMMT-O) origin are associated with poor prognosis. Suggestively epithelial-driven tumors, their treatment has shifted from anthracycline or ifosfamide-based towards taxane-based chemotherapy. It remains unclear whether this change associates with better outcomes. PATIENTS AND METHODS: A conjoined Australian and Swiss patient cohort of MMMT-E (N = 103) and MMMT-O (N = 17) was compared to patients with adenocarcinoma of the endometrium (EC, N = 172) and ovary (OC, N = 189). Clinicopathological characteristics, FIGO stage, first-line treatment, and patient outcomes were analyzed. The generated hypothesis was verified in an US-American cohort with high-grade serous ovarian cancer (HGSOC, N = 1290) and MMMT-O (N = 450) using immunohistochemistry and next-generation sequencing. RESULTS: Early stage I/II MMMT-E showed a survival plateau after 2.5 years, with no recurrence or death observed afterwards. Relapse-free survival was significantly worse in MMMT-E treated with platinum/taxanes (P = 0.024) compared to non-taxane regimen. Hypothesizing that also MMMT-O might benefit from an adjuvant non-paclitaxel regimen, a second independent cohort of MMMT-O and HGSOC patients was examined. p53 mutations dominated in both cancers with comparable frequency. PI3KCA and KRAS mutations were less frequent: they were more frequent in MMMT-O than in HGSOC (P = 0.015 and P = 0.018, respectively). MMMT-O responded better to a combination of carboplatin with anthracyclines than with taxanes (73.9% vs. 39.4%). CONCLUSION: Early stage I/II MMMT-E patients have excellent prognosis if no recurrence has appeared within the first 2.5 years. In MMMT-E, platinum/anthracycline or ifosfamide regimen associated with better outcomes than platinum/taxanes regimens. This might also apply to MMMT-O.

The impact of depression on adherence to organized and opportunistic breast cancer screening.

One in five women will experience depression over her lifetime, and one out of eight will develop breast cancer. We evaluated the effect of depression on adherence to mammography in Switzerland, where opportunistic and organized screening programs coexist. We analyzed data from 3206 women aged 50-69 who participated in the Swiss Health Survey 2012. We compared mammographic rates among women with no to mild versus moderate to severe depressive symptoms. The effect of the type of screening on the odds of undertaking a mammography was calculated using multivariable logistic regression analysis. Women with moderate to severe major depressive symptoms were more likely to have had a mammography in the previous 2 years than their nondepressed or less-depressed counterparts (51 vs. 39.2%, respectively, P = 0.005). In the multivariable analysis, women with no to mild major depression living in cantons with an organized screening program had an adjusted odds ratio of 2.7 (95% confidence interval: 2.30-3.17, P < 0.001) of having had a mammography within the past 24 months compared with those living in the regions with an opportunistic screening. The adjusted odds ratio for women with moderate to severe major depression was 4.21 (95% confidence interval: 2.13-8.33, P < 0.001). In Switzerland. adherence to mammographic screening among women with moderate to severe major depression is higher than among women with no or minimal major depressive symptoms. This increased adherence is even more pronounced in regions with organized screening.

Outcome in serous ovarian cancer is not associated with LATS expression.

BACKGROUND: Large tumor suppressor (LATS) proteins are putative tumor suppressors and poorly expressed associated with poor outcome in many cancers. A recent immunohistochemistry study showed that LATS protein expression correlated with poor outcome in serous ovarian cancer. MATERIALS AND METHODS: We analyzed LATS expression in various ovarian cancer transcriptomic data sets and immunohistochemically assessed LATS protein expression in a Swiss ovarian tumor cohort. Results were compared to clinicopathological characteristics and outcome. We also compared LATS protein expression in serous ovarian cancer cell lines to their EMT status (Western blotting) and drug sensitivity (MTT assay). RESULTS: The analysis of 15 different transcriptomic data sets showed that LATS2 was associated with poorer outcome, while LATS1 was irrelevant (HR = 1.19 and HR = 1.00, respectively). The TCGA-RNASeqV2 data set showed that low LATS1 and LATS2 were associated with better survival in serous ovarian carcinoma. Despite heterogeneity among the different data sets, LATS expression is not an indicator of survival in serous ovarian cancer and LATS2 expression may even be tumorigenic. LATS expression was neither associated with survival nor with the stage and grade in the Swiss cohort. It was low in cystadenoma, intermediate in carcinoma, and high in borderline tumors and was higher in serous than mucinous ovarian carcinoma. LATS protein expression extent was comparable in epithelial-, intermediate-, and mesenchymal-type ovarian cancer cells and was not associated with drug sensitivity. CONCLUSION: These results are largely incompatible with a tumor-suppressive function of LATS in ovarian cancer, and LATS protein level is also not an indicator for drug sensitivity and EMT status of ovarian cancer cells.

Tear Film Proteomics Reveal Important Differences Between Patients With and Without Ocular GvHD After Allogeneic Hematopoietic Cell Transplantation.

Purpose: To date, no biomarkers for ocular graft versus host disease (GvHD), a frequent complication following allogeneic hematopoietic cell transplantation (HCT), exist. In this prospective study, we evaluated the potential of human tear proteins as biomarkers for ocular GvHD. Methods: Tears from 10 patients with moderate-to-severe ocular GvHD were compared to 10 patients without ocular GvHD. After a full ocular surface clinical examination, tears were collected onto Schirmer strips and protein composition was analyzed by liquid chromatography tandem mass spectrometry. Statistical evaluation was performed using the Mann-Whitney U test to compare means and the false discovery rate method to adjust for multiple comparisons. Functional annotation of differentially expressed proteins was done with the PANTHER classification system. Results: We identified 282 proteins in tryptic digests of Schirmer strips; 79 proteins were significantly differentially expressed between the two groups, from which 54 were up- and 25 downregulated. The most upregulated proteins were classified as nucleic acid binding and cytoskeletal proteins, while the most extensively downregulated proteins belong to an array of classes including transfer and receptor proteins, enzyme modulators, and hydrolases. In addition to proteins already confirmed as differentially expressed in dry eye disease, we report changes in 36 novel proteins. Conclusions: This study reports the proteomic profile of tears in ocular GvHD for the first time and identifies a number of unique differentially expressed proteins. Further studies with a higher number of participants are necessary to confirm these results and to evaluate the reliability of these expression patterns in longitudinal studies.

Diaphragmatic smears are not of additional benefit in the detection of peritoneal spread in gynecological cancers.

Peritoneal biopsies (PB) and peritoneal washing (PW) are routine measures in abdominal staging of gynecological malignancies and are used particularly for the assessment of occult microscopic tumor spread to the peritoneal surface including the diaphragm. Cytological diaphragmatic smears (DS) have been suggested as a supplemental tool; however, they are not routinely taken and their usefulness is still unclear. The present study retrospectively evaluated whether DS provide an additional benefit over PB and PW for the detection of peritoneal malignancies in patients with gynecological cancer. The data from patients who underwent laparotomy for suspected gynecological cancer and had DS and either PB, PW or ascites were reviewed. Sensitivity and specificity, and the number upstaged patients were determined. A total of 43 patients were excluded due to benign diagnosis (those with negative DS or PW) and 2 out of the remaining had 2 carcinomas simultaneously. Among these 41 malignancies, DS were positive in 12, PW in 18 and PB in 19 cases. No case was DS-positive while negative for both PB and PW. Four cases were missed when only PB and 5 when only PW was performed. Notably, no case of peritoneal disease was identified solely on positive DS, indicating that all 23 positive cases (presence of occult peritoneal disease in 56.1%) were identified by PB and PW together (100% sensitivity; 62% specificity). In addition, none of the cases was upstaged solely on positive DS results. Taken together, these data demonstrated that DS do not present an additional benefit to PW and PB in the detection of peritoneal gynecological disease.

Higher retinal vessel oxygen saturation: investigating its relationship with macular oedema in retinitis pigmentosa patients.

PURPOSE: Primary objective-to investigate the effect of retinal vessel oxygen saturation (SO2) on macular oedema (ME) in retinitis pigmentosa (RP) patients. Secondary objective-to link the presence of ME to metabolic (oxygen saturation of retinal vessels, SO2), functional (multifocal electroretinography, mfERG) and structural (Spectral Domain Optical Coherent Tomography, SD-OCT) alterations in RP. DESIGN: Prospective, cross-sectional, non-interventional study. SUBJECTS: Patients with typical RP (N = 37) and controls (N = 19), who underwent retinal vessel Oximetry (RO), SD-OCT and mfERG, were included. METHODS: A computer-based program of the retinal vessel analyser unit (IMEDOS Systems UG, Jena, Germany) was used to measure SO2. We evaluated the mean SO2, in all major retinal arterioles (oxygen saturation in retinal arterioles, A-SO2, %) and venules (oxygen saturation in retinal venules, V-SO2, %). MfERG responses were averaged in zones (zone 1 (0-3°), zone 2 (3-8°) and zone 3 (8-15°)) and compared to corresponding areas of the OCT. The effect of ME on SO2 was evaluated dividing the RP in two subgroups: with clinical appearance of ME (ME-RP) and without it (no-ME-RP). MAIN OUTCOME MEASURES: Parallel recording and juxtaposition of metabolic (SO2) to structural (OCT) and functional-(mfERG) measures. Mean ( ± SD) A-SO2 and V-SO2 were higher in no-ME-RP (96.77% (±6.31) and 59.93% (±7.76)) and even higher in the ME-RP (99.82% (±6.21) and 65.63% (±7.63)), compared to controls (93.15% (±3.76) and 53.77% (±3.70), p ≤ 0.006). RESULTS: The subgroup ME-RP differed significantly from the subgroup no-ME-RP by increased A-SO2 and V-SO2, p ≤ 0.026. The presence of ME confirmed a different relationship between the altered SO2 and the vessel diameters, against the functional and structural parameters. CONCLUSION: Based on our results, the presence of macular oedema indicates a tendency toward greater alteration of the metabolic function in RP patients.

ABO blood groups as a prognostic factor for recurrence in ovarian and vulvar cancer.

The relationship between ABO blood groups (BG) and risk of incidence in cancers including gynecological cancers has been widely studied, showing increased incidence risk for BG A patients. As available data are inconsistent we investigated whether BG and their anti-glycan antibodies (anti-A and anti-B) have prognostic values in gynecological cancers. We retrospectively evaluated 974 patients with gynecological cancers in three cancer centers (Switzerland and Australia) between 1974 and 2014 regarding the relationships between clinico-pathological findings and the BG. Time to disease recurrence was significantly influenced by BG in patients with ovarian (n = 282) and vulvar (n = 67) cancer. BG O or B patients showed a significantly increased risk for ovarian cancer relapse compared to A, 59% and 82%, respectively (p = 0.045; HR O vs A = 1.59 (CI 1.01-2.51) and (p = 0.036; HR A vs B = 0.55 (CI 0.32-0.96). Median time to relapse for advanced stage (n = 126) ovarian cancer patients was 18.2 months for BG O and 32.2 for A (p = 0.031; HR O vs A = 2.07 (CI 1.07-4.02)). BG also significantly influenced relapse-free survival in patients with vulvar cancer (p = 0.002), with BG O tending to have increased relapse risk compared to A (p = 0.089). Blood groups hence associate with recurrence in ovarian and vulvar cancer: women with BG O seem to have a lower ovarian cancer incidence, however are more likely to relapse earlier. The significance of the BG status as a prognostic value is evident and may be helpful to oncologists in prognosticating disease outcome and selecting the appropriate therapy.

Efficacy of adjuvant chemotherapy with carboplatin for early triple negative breast cancer: a single center experience.

BACKGROUND: Anthracycline- and taxane-based adjuvant chemotherapies are the most frequently used systemic treatments for women with triple negative breast cancer (TNBC). Adding platinum derivatives in the neo-adjuvant setting has been shown to not only improve the pCR rates, but also the 3 year DFS for TNBC patients; however, data on platinum derivatives in the adjuvant setting are limited. METHODS: We conducted a retrospective, single-center study in a Swiss breast cancer cohort to evaluate the role of carboplatin in addition to standard adjuvant therapy (anthracyclines and/ or taxanes) in early TNBC patients. All patients with stage I-III TNBC who underwent primary breast surgery between 2004 and 2014 were included. RESULTS: Eighty-three patients were included in the analysis. Stage and grade were well balanced between patients treated with standard chemotherapy (N=54; cohort A) or standard chemotherapy plus carboplatin (N=29; cohort B). The median time to local relapse (LRFS) was 15.0 months in cohort A versus 16.0 months in cohort B (p=0.655). The median time to distant relapse (DRFS) was 29.5 months in cohort A versus 25.0 months in cohort B (p=0.606) There was also no difference in overall survival between the two cohorts (mean overall survival 98 and 91 months, respectively; p=0.208). DISCUSSION: Our data suggest that in an unselected cohort of early TNBC patients, the addition of carboplatin in the adjuvant setting may not be beneficial with respect to relapse-free and overall survival. Further prospective trials to evaluate the addition of platinum in the adjuvant setting are warranted, especially to define subgroups of TNBC patients, which might benefit from carboplatin therapy.

Tissue glycomics distinguish tumour sites in women with advanced serous adenocarcinoma.

In the era of precision medicine, the tailoring of cancer treatment is increasingly important as we transition from organ-based diagnosis towards a more comprehensive and patient-centric molecular diagnosis. This is particularly the case for high-grade serous adenocarcinomas of the ovary and peritoneum, which are commonly diagnosed at an advanced stage, and collectively treated and managed similarly. We characterized the N- and O-glycome of serous ovarian (OC) and peritoneal cancer (PC) tissues using PGC-LC-ESI-IT-MS/MS profiling and validated the discriminatory glycans and their corresponding glyco-gene expression levels using cell lines and transcriptomic data from 232 patients. Overall, the N- and O-glycan repertoires of both cancer types were found to comprise mostly of α2,6-sialylated glycan structures, with the majority of N-glycans displaying the biantennary mono- and disialylation as well as bisecting-type biantennary glycans. The MS profiling by PGC-LC also revealed several glycan structural isomers that corresponded to LacdiNAc-type (GalNAcß1-4GlcNAc) motifs that were unique to the serous ovarian cancers and that correlated with elevated gene expression of B4GALNT3 and B4GALNT4 in patients with serous cancer. Statistical evaluation of the discriminatory glycans also revealed 13 N- and 3 O-glycans (P < 0.05) that significantly discriminated tumour-sampling sites, with LacdiNAc-type N-glycans (m/z 1205.02- and m/z 1059.42- ) being associated with ovarian-derived cancer tissue and bisecting GlcNAc-type (m/z 994.92- ) and branched N-glycans (m/z 1294.02- and m/z 1148.42- ) upregulated at the metastatic sites. Hence, we demonstrate for the first time that OC and PC display distinct molecular signatures at both their glycomic and transcriptomic levels. These signatures may have potential utility for the development of accurate diagnosis and personalized treatments.

MELK expression in ovarian cancer correlates with poor outcome and its inhibition by OTSSP167 abrogates proliferation and viability of ovarian cancer cells.

OBJECTIVE: Maternal embryonic leucine-zipper kinase (MELK) shows oncogenic properties in basal-like breast cancer, a cancer subtype sharing common molecular features with high-grade serous ovarian cancer. We examined the potential of MELK as a molecular and pharmacological target for treatment of epithelial ovarian cancer (EOC). METHODS/MATERIALS: Bioinformatic analysis was performed on nine OC transcriptomic data sets totaling 1241 patients. Effects of MELK depletion by shRNA or inhibition by OTSSP167 in cell lines were assessed by colony formation and MTT (proliferation) assays, Western blotting (apoptosis), and flow cytometry (cell cycle analysis). RESULTS: Elevated MELK expression was correlated with histological grading (n=6 data sets, p<0.05) and progression-free survival (HR 5.73, p<0.01) in OC patients and elevated MELK expression in other cancers with disease-free survival (n=3495, HR 1.071, p<0.001). Inhibition or depletion of MELK reduced cell proliferation and anchorage-dependent and -independent growth in various OC cell lines through a G2/M cell cycle arrest, eventually resulting in apoptosis. OTSSP167 retained its cytotoxicity in Cisplatin- and Paclitaxel-resistant IGROV1 and TYK-nu OC cells and sensitized OVCAR8 cells to Carboplatin but not Paclitaxel. CONCLUSION: MELK inhibition by OTSSP167 may thus present a strategy to treat patients with aggressive, progressive, and recurrent ovarian cancer.

Canaloplasty with Stegmann Canal Expander for primary open-angle glaucoma: two-year clinical results.

PURPOSE: To examine longer-term postsurgical safety and efficacy of a new expander for Schlemm's canal. METHODS: In a non-comparative, prospective study, 42 White patients with medically uncontrolled primary open-angle glaucoma (POAG) underwent primary canaloplasty with >2-year follow-up. The bleb-independent procedure comprised catheter-assisted canaloplasty and implantation of two Stegmann Canal Expanders to maintain trabecular distension and canal patency over 180°. Intraocular pressure (IOP), glaucoma medication use and complications were assessed. RESULTS: Mean IOP was 26.8 ± 5.6 mmHg presurgery, 12.8 ± 1.5 mmHg at 6 months, 13.2 ± 1.2 mmHg at 12 months and 13.3 ± 2.5 mmHg at 24 months (p < 0.001). Rate of complete success, defined as IOP ≤21, ≤18 and ≤16 mmHg and a ≥ 30% IOP reduction, was 85% (95% CI: 0.76-0.95), 85% (0.76-0.95) and 82% (0.70-0.96) at 12 months and 83% (0.73-0.94), 80% (0.70-0.92) and 80% (0.70-0.92) at 24 months. Preoperative factors were not significant predictors of ≤16 mmHg IOP reduction: IOP (hazard ratio [HR]: 0.68; 95% CI: 0.44-1.04; p = 0.08), mean visual defect (1.06; 0.90-1.20; p = 0.47), number of medications (0.59; 0.17-2.14; p = 0.42) and age (0.96; 0.87-1.13; p = 0.41). Number of medications dropped from 2.8 ± 0.4 presurgery to 0.2 ± 0.5 postsurgery (p < 0.001). Mean preoperative best-corrected visual acuity was 0.19 ± SD 0.21 (range: 0-1.6), and logMAR was similar to 0.23 ± 0.16 (range: 0-1.6; p = 0.42) after a mean follow-up of 27.4 months. Complications included peripheral Descemet's membrane detachment (7.2%) and trimming of the expander (4.7%) during surgery, and transient microhyphaema (23.8%) and IOP elevation (7.2%) postsurgery. CONCLUSION: Canaloplasty with the Stegmann Canal Expander was a safe and effective procedure to reduce IOP in White patients with moderate to advanced POAG.

Fourfold increase in prevalence of gestational diabetes mellitus after adoption of the new International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria.

BACKGROUND: The aim was to evaluate the influence of the new International Association of Diabetes and Pregnancy Study Groups (IADPSG) guidelines for screening of gestational diabetes mellitus (GDM) on GDM prevalence in a cohort from a Swiss tertiary hospital. METHODS: This was a retrospective cohort study involving all pregnant women who were screened for GDM between 24 and 28 weeks of gestation. From 2008 until 2010 (period 1), a two-step approach with 1-h 50 g glucose challenge test (GCT) was used, followed by fasting, 1- and 2-h glucose measurements after a 75 g oral glucose tolerance test (OGTT) in case of a positive GCT. From 2010 until 2013 (period 2), all pregnant women were tested with a one-step 75 g OGTT according to new IADPSG guidelines. In both periods, women with risk factors could be screened directly with a 75 g OGTT in early pregnancy. RESULTS: Overall, 647 women were eligible for the study in period 1 and 720 in period 2. The introduction of the IADPSG criteria resulted in an absolute increase of GDM prevalence of 8.5% (3.3% in period 1 to 11.8% in period 2). CONCLUSIONS: The adoption of the IADPSG criteria resulted in a considerable increase in GDM diagnosis in our Swiss cohort. Further studies are needed to investigate if the screening is cost effective and if treatment of our additionally diagnosed GDM mothers might improve short-term as well as long-term outcome.

Blood Plasma-Derived Anti-Glycan Antibodies to Sialylated and Sulfated Glycans Identify Ovarian Cancer Patients.

Altered levels of naturally occurring anti-glycan antibodies (AGA) circulating in human blood plasma are found in different pathologies including cancer. Here the levels of AGA directed against 22 negatively charged (sialylated and sulfated) glycans were assessed in high-grade serous ovarian cancer (HGSOC, n = 22) patients and benign controls (n = 31) using our previously developed suspension glycan array (SGA). Specifically, the ability of AGA to differentiate between controls and HGSOC, the most common and aggressive type of ovarian cancer with a poor outcome was determined. Results were compared to CA125, the commonly used ovarian cancer biomarker. AGA to seven glycans that significantly (P<0.05) differentiated between HGSOC and control were identified: AGA to top candidates SiaTn and 6-OSulfo-TF (both IgM) differentiated comparably to CA125. The area under the curve (AUC) of a panel of AGA to 5 glycans (SiaTn, 6-OSulfo-TF, 6-OSulfo-LN, SiaLea, and GM2) (0.878) was comparable to CA125 (0.864), but it markedly increased (0.985) when combined with CA125. AGA to SiaTn and 6-OSulfo-TF were also valuable predictors for HGSOC when CA125 values appeared inconclusive, i.e. were below a certain threshold. AGA-glycan binding was in some cases isotype-dependent and sensitive to glycosidic linkage switch (α2-6 vs. α2-3), to sialylation, and to sulfation of the glycans. In conclusion, plasma-derived AGA to sialylated and sulfated glycans including SiaTn and 6-OSulfo-TF detected by SGA present a valuable alternative to CA125 for differentiating controls from HGSOC patients and for predicting the likelihood of HGSOC, and may be potential HGSOC tumor markers.

Epigenetic activation of MGAT3 and corresponding bisecting GlcNAc shortens the survival of cancer patients.

Bisecting GlcNAc on N-glycoproteins is described in E-cadherin-, EGF-, Wnt- and integrin- cancer-associated signaling pathways. However, the mechanisms regulating bisecting GlcNAc expression are not clear. Bisecting GlcNAc is attached to N-glycans through beta 1-4 N-acetylglucosaminyl transferase III (MGAT3), which is encoded by two exons flanked by high-density CpG islands. Despite a recently described correlation of MGAT3 and bisecting GlcNAc in ovarian cancer cells, it remains unknown whether DNA methylation is causative for the presence of bisecting GlcNAc. Here, we narrow down the regulatory genomic region and show that reconstitution of MGAT3 expression with 5-Aza coincides with reduced DNA methylation at the MGAT3 transcription start site. The presence of bisecting GlcNAc on released N-glycans was detected by mass spectrometry (LC-ESI-qTOF-MS/MS) in serous ovarian cancer cells upon DNA methyltransferase inhibition. The regulatory impact of DNA methylation on MGAT3 was further evaluated in 18 TCGA cancer types (n = 6118 samples) and the results indicate an improved overall survival in patients with reduced MGAT3 expression, thereby identifying long-term survivors of high-grade serous ovarian cancers (HGSOC). Epigenetic activation of MGAT3 was also confirmed in basal-like breast cancers sharing similar molecular and genetic features with HGSOC. These results provide novel insights into the epigenetic regulation of MGAT3/bisecting GlcNAc and demonstrate the importance of N-glycosylation in cancer progression.

Improved Detection Rate of Ovarian Cancer Using a 2-Step Triage Model of the Risk of Malignancy Index and Expert Sonography in an Outpatient Screening Setting.

OBJECTIVE: Preoperative assessment of adnexal masses with ultrasound has been shown to be time-, cost-effective, and specific. When used in combination with the menopausal status and the tumor marker CA125, the risk of malignancy index (RMI) can be calculated, allowing appropriate preoperative triage of patients to a gynecologist or a gynecological oncologist. Moreover, it allows for accurate planning of the required surgical procedure (laparoscopy vs laparotomy). METHODS: A large general gynecologic ultrasonic database retrospectively identified 5218 patients for a 14-year period who presented to the outpatient clinic with an adnexal mass. Additional data (menopausal status, histology, CA125 values) were available in 1108 of these patients. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. The results were then compared with previously published data from a large Australian gynecological cancer center (GCC, n = 204). RESULTS: With the use of an RMI cutoff of 200, malignant ovarian tumors were correctly triaged to a gynecologic oncologist in 123 of 172 cases, leading to a sensitivity of 72% and specificity of 92% in our general outpatient clinic population compared with a sensitivity of 84% and a specificity of 77% in the GCC high-risk population. The negative predictive value was 95% compared with only 85% in the GCC cohort. We hypothesize that improvement of the overall detection rate of malignancy could be improved from 72% to 85% using a 2-step model, referring patients with an ultrasonic score of 3 to an experienced sonographer who uses pattern recognition. CONCLUSIONS: The RMI is an easy and reliable tool for the accurate triage of adnexal masses. Its value is higher in an unselected gynecological outpatient setting. Our proposed 2-step model including expert pattern recognition could influence particularly the detection rate in borderline and early-stage ovarian cancers and overcome the limitations of the tumor marker CA125.

Inter-device size variation of small choroidal nevi measured using stereographic projection ultra-widefield imaging and optical coherence tomography.

PURPOSE: Our purpose was to compare the tumor sizes of small choroidal nevi using ultra-widefield imaging (UWF) and different optical coherence tomography systems. METHODS: Thirteen choroidal nevi were measured using automatic and manual segmentation techniques, including enhanced depth imaging spectral-domain optical coherence tomography (EDI-SDOCT) and 1050 nm swept source OCT (SSOCT), to compare to measurements obtained using the Optos projection ultra-widefield fundus (UWF) imaging technique. Segmentation artifacts were evaluated for all 13 cases, alongside an additional 12 choroidal nevi, using SSOCT. RESULTS: In tumor eyes, segmentation artifacts for the choroid-sclera interface were found in 42 % of SSOCT scans. EDI-SDOCT can underestimate tumor dimensions and differs up to -8.41 % compared to UWF imaging and by 1.25 % compared to SSOCT cases. The horizontal length of the nevi showed an average difference between EDI-SDOCT and SSOCT of ± 9.38 %. Measured markers showed an average difference in length of ± 12.51 %. The average tumor thickness showed a difference of ± 11.47 %. Comparisons between EDI-SDOCT/UWF, SSOCT/EDI-SDOCT, and marker EDI-SDOCT/SSOCT showed significant mean differences of -122 µm (CI: -212 to -31 µm, p = 0.013), 134 µm (CI: 65-203 µm, p = 0.0012), and -193 µm (CI: -345 to -41 µm, p = 0.017), whereas SSOCT/UWF showed no significant difference with a measurement of 13 µm (CI: -69-95 µm, p = 0.74). CONCLUSIONS: Automatic segmentation of nevi requires much caution, because a choroidal tumor can trigger many artifacts. It would be beneficial to monitor choroidal nevi using the same type of OCT technology, because a tumor is displayed differently.