Clinical outcomes of pelvic exenteration for gynecologic malignancies.

Objectives: The aim of this study was to analyze morbidity and survival after pelvic exenteration for gynecologic malignancies and evaluate prognostic factors influencing postoperative outcome.

Methods: We retrospectively reviewed all patients who underwent a pelvic exenteration at the departments of gynecologic oncology of three tertiary care centers in the Netherlands, the Leiden University Medical Centre, the Amsterdam University Medical Centre, and the Netherlands Cancer Institute, during a 20-year period. We determined postoperative morbidity, 2- and 5-year overall survival (OS) and 2- and 5-year progression free survival (PFS), and investigated parameters influencing these outcomes.

Quantitative Phosphoproteomic Analysis Reveals Dendritic Cell- Specific STAT Signaling After α2-3-Linked Sialic Acid Ligand Binding.

Dendritic cells (DCs) are key initiators of the adaptive immunity, and upon recognition of pathogens are able to skew T cell differentiation to elicit appropriate responses. DCs possess this extraordinary capacity to discern external signals using receptors that recognize pathogen-associated molecular patterns. These can be glycan-binding receptors that recognize carbohydrate structures on pathogens or pathogen-associated patterns that additionally bind receptors, such as Toll-like receptors (TLRs).

Tn Antigen Expression Contributes to an Immune Suppressive Microenvironment and Drives Tumor Growth in Colorectal Cancer.

Expression of the tumor-associated glycan Tn antigen (αGalNAc-Ser/Thr) has been correlated to poor prognosis and metastasis in multiple cancer types. However, the exact mechanisms exerted by Tn antigen to support tumor growth are still lacking. One emerging hallmark of cancer is evasion of immune destruction.

FUT9-Driven Programming of Colon Cancer Cells towards a Stem Cell-Like State.

Cancer stem cells (CSCs) are located in dedicated niches, where they remain inert to chemotherapeutic drugs and drive metastasis. Although plasticity in the CSC pool is well appreciated, the molecular mechanisms implicated in the regulation of cancer stemness are still elusive. Here, we define a fucosylation-dependent reprogramming of colon cancer cells towards a stem cell-like phenotype and function.

Oncological outcome of surgical management in patients with recurrent uterine cancer-a multicenter retrospective cohort study-CEEGOG EX01 Trial.

Objectives: To assess the survival of patients who have received an operation for recurrent cervical and endometrial cancer and to determine prognostic variables for improved oncologic outcome.

Methods: A retrospective multicenter analysis of the medical records of 518 patients with cervical (N = 288) or endometrial cancer (N = 230) who underwent surgery for disease recurrence and who had completed at least 1 year of follow-up.

Results: The median survival reached 57 months for patients with cervical cancer and 113 months for patients with endometrial cancer after surgical treatment of recurrence (p = 0.

Differential effects of anaphylatoxin C5a on antigen presenting cells, roles for C5aR1 and C5aR2.

The anaphylatoxin C5a is well-known for its role as chemoattractant and contributes to immune cell recruitment into inflamed tissue and local inflammation. C5a has recently been implicated in modulation of antigen presenting cell function, such as macrophages and dendritic cells, which are pivotal for T cell activation and final T cell effector function. The published data on the effect of C5a on APC function and subsequent adaptive immune responses are in part conflicting, as both pro and anti-inflammatory effects have been described.

Disruption of sialic acid metabolism drives tumor growth by augmenting CD8 T cell apoptosis.

Sialylated glycan structures are known for their immunomodulatory capacities and their contribution to tumor immune evasion. However, the role of aberrant sialylation in colorectal cancer and the consequences of complete tumor desialylation on anti-tumor immunity remain unstudied. Here, we report that CRISPR/Cas9-mediated knock out of the CMAS gene, encoding a key enzyme in the sialylation pathway, in the mouse colorectal cancer MC38 cell line completely abrogated cell surface expression of sialic acids (MC38-Sia ) and, unexpectedly, significantly increased in vivo tumor growth compared to the control MC38-MOCK cells.

Anaphylatoxin C5a Regulates 6-Sulfo-LacNAc Dendritic Cell Function in Human through Crosstalk with Toll-Like Receptor-Induced CREB Signaling.

Activation of antigen-presenting dendritic cells (DCs) and the complement system are essential early events in the immune defense against invading pathogens. Recently, we and others demonstrated immunological crosstalk between signaling from receptors recognizing complement activation products and PAMPs on DCs. This affects DC effector function, as demonstrated by the finding that C5a prevents induction of pro-inflammatory cytokines by toll-like receptor (TLR) ligands in human monocyte-derived DCs (moDCs).

TLR4 and C5aR crosstalk in dendritic cells induces a core regulatory network of RSK2, PI3Kβ, SGK1, and FOXO transcription factors.

Crosstalk between complement component 5a receptors (C5aRs) and TLRs in dendritic cells (DCs) occurs upon pathogen invasion; however, studies on C5aR and TLR crosstalk mainly focused on the modulating effect of C5a on TLR-induced cytokine production. To elucidate the breadth of C5aR and TLR4 crosstalk, the effect of simultaneous treatment with C5a and LPS was investigated in human monocyte-derived DCs (moDCs) 2 h after stimulation using whole transcriptome sequencing analysis. Although the effect of C5a on hallmark genes defining TLR4-induced DC maturation was limited at this time point, RNA sequencing analysis revealed a great variety of novel C5a targets, of which many interfere with TLR4-mediated immune activation.

The performance of Dynamic Spectral Imaging colposcopy depends on indication for referrals.

OBJECTIVE. A previous study has shown that Dynamic Spectral Imaging (DSI) colposcopy increases the sensitivity of the colposcopic examination in women referred with abnormal cytology. In this study we have reanalyzed the performance of DSI and conventional colposcopy for new referral conditions and for low-grade cytology referrals versus high-grade cytology referrals.

Initial Benchmarking of the Quality of Medical Care in Childhood-Onset Systemic Lupus Erythematosus.

Objective: To assess the quality of medical care in childhood-onset systemic lupus erythematosus (SLE) at tertiary pediatric rheumatology centers as measured by observance of SLE quality indicators (SLE-QIs).

Methods: International consensus has been achieved for childhood-onset SLE-QIs capturing medical care provision in 9 domains: diagnostic testing, education of cardiovascular (CV) risk and lifestyles, lupus nephritis (LN), medication management, bone health, ophthalmologic surveillance, transition, pregnancy, and vaccination. Using medical record information, the level of performance of these childhood-onset SLE-QIs was assessed in childhood-onset SLE populations treated at 4 tertiary pediatric rheumatology centers in the US, 2 in Brazil, and 1 center in India.

The diagnostic process of cervical cancer; areas of good practice, and windows of opportunity.

Objective: Despite an extensive screening programme in The Netherlands, some cases of cervical cancer are still diagnosed in late stages of disease. The aim of the present study was to investigate which elements in the diagnostic process of cervical cancer may be improved.

Methods: This is a retrospective study of 120 patients with cervical cancer diagnosed between January 1st 2008 and June 1st 2010 at the University Medical Center Utrecht.

Childhood-onset lupus with clinical neurocognitive dysfunction shows lower streamline density and pairwise connectivity on diffusion tensor imaging.

Objectives: The objective of this report is to use diffusion-tensor imaging (DTI) for investigating white-matter connectivity changes associated with neurocognitive dysfunction in childhood-onset lupus (cSLE-NCD) as measured by formal neuropsychological testing.

Methods: DTI was performed in six individuals with (cSLE-NCD) and nine without neurocognitive dysfunction (cSLE-noNCD) as well as 14 healthy controls. Presence of neurocognitive deficits was identified by formal neuropsychological testing.

Women's Preferences of Dynamic Spectral Imaging Colposcopy.

Background: The focus of testing the dynamic spectral imaging (DSI) colposcope has been on the technical characteristics and clinical performance. However, aspects from a patient's perspective are just as important.

Methods: This study was designed as a substudy of the DSI validation study, a prospective comparative, multicenter clinical trial to assess the clinical performance of DSI colposcopy.

Blood-based candidate biomarkers of the presence of neuropsychiatric systemic lupus erythematosus in children.

Objective: To examine select brain-reactive proteins for their usefulness to serve as blood-based biomarkers in the screening for neurocognitive deficits in childhood-onset systemic lupus erythematosus (cSLE-NCD).

Methods: Patients withcSLE (n=40) were studied longitudinally (month 1; month 18): working memory, psychomotor speed and visuoconstructional ability were assessed using formal neurocognitive testing to determine the presence of cSLE-NCD. Patients also completed the computerised Paediatric Automated Neuropsychological Assessment Metrics.

Pelvic lymphadenectomy improves survival in patients with cervical cancer with low-volume disease in the sentinel node: a retrospective multicenter cohort study.

Objective: In this study, we aimed to describe the value of pelvic lymph node dissection (LND) after sentinel lymph node (SN) biopsy in early-stage cervical cancer.

Methods: We performed a retrospective multicenter cohort study in 8 gynecological oncology departments. In total, 645 women with International Federation of Gynecology and Obstetrics stage IA to IIB cervical cancer of squamous, adeno, or adenosquamous histologic type who underwent SN biopsy followed by pelvic LND were enrolled in this study.

Detection of cervical cancer recurrence during follow-up: a multivariable comparison of 9 frequently investigated serum biomarkers.

Objective: To assess the diagnostic accuracy and model the optimal combination of commonly studied serum biomarkers aimed at identifying recurrence in cervical cancer patients.

Methods: From a systematic literature search, nine biomarkers (CA-15.3, CA-125, CEA, CYFRA 21-1, hsCRP, IL-6, SCC-Ag, TNF-α and VEGF) were selected for a serum analysis.

Bilateral ultrastaging of sentinel lymph node in cervical cancer: Lowering the false-negative rate and improving the detection of micrometastasis.

Objective: To evaluate the sensitivity of sentinel node (SN) ultrastaging and to define parameters that may reduce the overall false-negative rate in women with early-stage cervical cancer.

Methods: We analyzed data from a large retrospective multicenter cohort group with FIGO stages IA-IIB cervical cancer in whom at least one SN was identified and systematic pelvic lymphadenectomy was uniformly performed. All who were SN negative by initial evaluation were subjected to ultrastaging.

Genomic aberrations relate early and advanced stage ovarian cancer.

Background: Because of the distinct clinical presentation of early and advanced stage ovarian cancer, we aim to clarify whether these disease entities are solely separated by time of diagnosis or whether they arise from distinct molecular events.

Methods: Sixteen early and sixteen advanced stage ovarian carcinomas, matched for histological subtype and differentiation grade, were included. Genomic aberrations were compared for each early and advanced stage ovarian cancer by array comparative genomic hybridization.

Crosstalk between Toll like receptors and C5a receptor in human monocyte derived DCs suppress inflammatory cytokine production.

The complement anaphylatoxin, C5a has been implicated in regulation of adaptive immune responses through modulation of APC function as shown mainly in studies in mice. C5a was shown to enhance cytokine production in immature DCs, but the effect of C5a on DC function during DC activation has not been elucidated in human. In this study we investigated the effect of C5a on human monocyte derived DCs when simultaneously stimulated with TLR ligands.

Long-term CIN3+ risk in women with abnormal cytology; role of hrHPV testing.

Background: Many studies have examined the short-term value of high-risk human papillomavirus (hrHPV) testing in predicting cumulative risk of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+). This study focuses on long-term CIN3+ risk after initial wait and see policy.

Methods: A total of 342 women with abnormal cytology of borderline/mild dyskaryosis (BMD) or worse (>BMD), included between 1990 and 1992, were followed-up by cytology and hrHPV testing until 1996 and monitored by cytology thereafter.

Agreement between colposcopic impression and histological diagnosis among human papillomavirus type 16-positive women: a clinical trial using dynamic spectral imaging colposcopy.

Objective: To investigate the agreement between conventional colposcopic impression, dynamic spectral imaging (DSI) colposcopy and histology, for human papillomavirus type 16-positive (HPV16(+)) and non-16 high-risk (hr) HPV(+) women.

Design: Prospective, comparative, multicentre clinical trial.

Setting: Three colposcopy clinics in the Netherlands.

Prognostic significance of low volume sentinel lymph node disease in early-stage cervical cancer.

Objective: Evaluate prognostic significance of low volume disease detected in sentinel nodes (SN) of patients with early stages cervical cancer. Although pathologic ultrastaging of SN allows for identification of low volume disease, including micro-metastasis and isolated tumor cells (ITC), in up to 15% of cases, prognostic significance of these findings is unknown.

Methods: A total of 645 records from 8 centers were retrospectively reviewed.