Differences in Treatment and Outcome of Pancreatic Adenocarcinoma Stage I and II in the EURECCA Pancreas Consortium.

BACKGROUND: The EUropean REgistration of Cancer CAre (EURECCA) consortium aims to investigate differences in treatment and to improve cancer care through Europe. The purpose of this study was to compare neo- and adjuvant chemotherapy (ACT) and outcome after tumor resection for pancreatic adenocarcinoma stage I and II in the EURECCA Pancreas consortium. METHODS: The eight, collaborating national, regional, and single-center partners shared their anonymized dataset. Patients diagnosed in 2012-2013 who underwent tumor resection for pancreatic adenocarcinoma stage I and II were investigated with respect to treatment and survival and compared using uni- and multivariable logistic and Cox regression analyses. All comparisons were performed separately per registry type: national, regional, and single-center registries. RESULTS: In total, 2052 patients were included. Stage II was present in the majority of patients. The use of neo-ACT was limited in most registries (range 2.8-15.5%) and was only different between Belgium and The Netherlands after adjustment for potential confounders. The use of ACT was different between the registries (range 40.5-70.0%), even after adjustment for potential confounders. Ninety-day mortality was also different between the registries (range 0.9-13.6%). In multivariable analyses for overall survival, differences were observed between the national and regional registries. Furthermore, patients in ascending age groups and patients with stage II showed a significant worse overall survival. CONCLUSIONS: This study provides a clear insight in clinical practice in the EURECCA Pancreas consortium. The differences observed in (neo-)ACT and outcome give us the chance to further investigate the best practices and improve outcome of pancreatic adenocarcinoma.

The effect of arm position and bed adjustment on comfort and pressure under the shoulders in people with tetraplegia: a randomized cross-over study.

STUDY DESIGN: Randomized, within-in participant cross-over study. OBJECTIVE: The purpose of this study was to determine the effect on comfort and pressure of lying with the shoulders and bed in different positions for people with tetraplegia. SETTING: Rehabilitation hospital. METHODS: Twenty people with tetraplegia were tested lying supine with the shoulders and bed in seven different positions. The positions used a combination of three arm and two bed positions. Six of the positions reflected what is commonly recommended in acute spinal cord injury units including a crucifix-type position. The seventh position was selected by participants and reflected their preferred sleeping position. There were five outcomes: general comfort, shoulder comfort, participant choice of preferred position, peak pressure under the shoulders and areal pressure under the shoulders. Pressure was measured using a pressure mapping system and comfort using a visual analogue scale (VAS). RESULTS: The participants reported significantly higher (P<0.01) general comfort and shoulder comfort in their self-selected position compared with all other positions. There was no statistical difference in peak pressure (P=0.15) or areal pressure (P=0.08) under the shoulders between the seven positions. Most participants indicated that they preferred to lie with their shoulders adducted and internally rotated and the hands either by their sides or on their stomachs. CONCLUSION: The position of the shoulders has little effect on pressure but a notable effect on comfort. Participants preferred to sleep with their arms beside their bodies, not with their arms in a crucifix position as commonly advocated.

Highly versatile, two-color setup for high-order harmonic generation using spatial light modulators.

We present a novel, interferometric, two-color, high-order harmonic generation setup based on a turn-key Ytterbium-doped femtosecond laser source and its second harmonic. Each interferometer arm contains a spatial light modulator with individual capabilities to manipulate the spatial beam profiles and to stabilize the relative delay between the fundamental and the second harmonic. In addition, separate control of the relative power and focusing geometries of the two color beams is implemented to conveniently perform automated scans of multiple parameters. A live diagnostics system gives continuous information during ongoing measurements.

Advances in rectal cancer: Real-world evidence suggests limited gains in prognosis for elderly patients.

BACKGROUND: Rectal cancer treatment has improved considerably due to the introduction of total meso-rectal excision, radio-chemotherapy, and high-resolution imaging. The aim of this observational cohort study was to quantify the effectiveness of these advances using high-quality data from a representative cohort of patients. METHODS: 20 281 non-metastasized cases retrieved from the Munich Cancer Registry database were divided into three time periods corresponding to before (1988-1997), partial (1998-2007), and full implementation (2008-2019) of clinical advances. Early-onset (<50 yrs.), middle-aged, elderly patient subgroups (> 70 yrs.) were compared. The overall effectiveness of evidence-based guideline adherence was also examined. RESULTS: Median survival improved by 1.5 yrs. from the first to the last time period. Relative survival increased from 74.9% (5-yr 95%CI[73.3 - 76.6]) to 79.2% (95%CI[77.8 - 80.5]). The incidence of locoregional recurrences was reduced dramatically by more than half (5-yr 17.7% (95%CI[16.5 - 18.8]); 6.7% (95%CI[6.1 - 7.3])). Gains in 5-yr relative survival were limited to early-onset and middle-aged patients with no significant improvement seen in elderly patients (Female 68.6% [63.9 - 73.3] to 67.6% [64.0 - 71.2]; Male 71.7% [65.9 - 77.4] to 74.0% [70.8 - 77.2]). CONCLUSIONS: Real-world evidence suggests that recent treatment advances have lead to an increase in prognosis for rectal cancer patients. However, more effort should be made to improve the implementation of new developments in elderly patients. Especially considering, that these cases represent a growing majority of diagnosed patients.

Is it possible to agree on a value for inorganic arsenic in food? The outcome of IMEP-112.

Two of the core tasks of the European Union Reference Laboratory for Heavy Metals in Feed and Food (EU-RL-HM) are to provide advice to the Directorate General for Health and Consumers (DG SANCO) on scientific matters and to organise proficiency tests among appointed National Reference Laboratories. This article presents the results of the 12th proficiency test organised by the EU-RL-HM (IMEP-112) that focused on the determination of total and inorganic arsenic in wheat, vegetable food and algae. The test items used in this exercise were: wheat sampled in a field with a high concentration of arsenic in the soil, spinach (SRM 1570a from NIST) and an algae candidate reference material. Participation in this exercise was open to laboratories from all around the world to be able to judge the state of the art of the determination of total and, more in particular, inorganic arsenic in several food commodities. Seventy-four laboratories from 31 countries registered to the exercise; 30 of them were European National Reference Laboratories. The assigned values for IMEP-112 were provided by a group of seven laboratories expert in the field of arsenic speciation analysis in food. Laboratory results were rated with z and ζ scores (zeta scores) in accordance with ISO 13528. Around 85 % of the participants performed satisfactorily for inorganic arsenic in vegetable food and 60 % did for inorganic arsenic in wheat, but only 20 % of the laboratories taking part in the exercise were able to report satisfactory results in the algae test material.

Lactobacillus crispatus DSM25988 as novel bioactive agent to co-aggregate Streptococcus pyogenes and to exclude it by binding to human cells.

Streptococcus pyogenes, a group A streptococcus, is the major bacterial pathogen responsible for acute bacterial infection of the human oropharynx and the causative agent of scarlet fever. Estimates of the global burden of S. pyogenes related diseases revealed 616 million cases of pharyngitis, and at least 517,000 deaths due to severe invasive diseases and sequelae. Here we describe Lactobacillus crispatus DSM25988 that was identified among hundreds of Lactobacillus strains (referring to all organisms that were classified as Lactobacillaceae until 2020) showing ability to prevent adhesion of S. pyogenes to Detroit 562 cells, and to exhibit a masking and co-aggregating effect on S. pyogenes in vitro. L. crispatus DSM25988 also inhibits invasion of cultured human epithelial pharyngeal cells by S. pyogenes. Competitive binding to fibronectin might be involved in the inhibition process. Antiviral activity of the L. crispatus DSM25988 cells were identified in an in vitro cell model demonstrating that L. crispatus effectively excludes viruses from epithelial cells using SARS-CoV2 proteins as a model. This finding points to the potential of DSM25988 to protect cells from virus infection. Biological activity is retained in heat treated cells. The heat-treated Lactobacillus strain was further developed into functional throat lozenges, wherein its biological activity is stably maintained in the formulation. Lozenges containing L. crispatus DSM25988 underwent testing in an uncontrolled, prospective user study in 44 subjects with symptoms of sore throat for a period of up to 14 days. The study data shows promising safety and efficacy of the medical device when used against symptoms of sore throat like scratchy feeling, hoarse voice and swallowing pain.

Outcome of children with oligoarticular juvenile idiopathic arthritis compared to polyarthritis on methotrexate- data of the German BIKER registry.

BACKGROUND: Oligoarticular juvenile idiopathic arthritis (oligoJIA) is the most commonly diagnosed category of chronic arthritis in children. Nevertheless, there are no evidence- based guidelines for its treatment, in particular for the use of methotrexate (MTX). The primary objective of this analysis is to evaluate the outcomes in patients with persistent oligoJIA compared to those with extended oligoJIA and rheumatoid factor (RF) negative polyarthritis treated with methotrexate. METHODS: Patients with persistent or extended oligoJIA or RF negative PA recorded in the Biologics in Pediatric Rheumatology Registry (BiKeR), receiving methotrexate for the first time were included in the analyses. Efficacy was determined using the Juvenile Arthritis Disease Activity Score 10 (JADAS 10). Safety assessment included the documentation of adverse and serious adverse events. RESULTS: From 2005 through 2011, 1056 patients were included: 370 patients with persistent oligoJIA, 221 patients with extended oligoJIA and 467 patients with RF negative PA. Therapeutic efficacy was observed following the start of methotrexate. Over a period of 24 months JADAS-minimal disease activity (JADAS ≤2) was reached in 44% of patients with persistent oligoJIA, 38% with extended oligoJIA, 46% with RF negative PA, JADAS-remission defined as JADAS ≤1 was reached in 33% of patients with persistent oligoJIA, 29% with extended oligoJIA and 35% (RF negative PA). Patients with extended oligoJIA achieved JADAS remission significantly later and received additional biologic disease-modifying drugs significantly more often than patients with persistent oligoJIA or RF negative PA (p < 0.001). Tolerability was comparable. New onset uveitis occurred in 0.3 to 2.2 per 100 patient years. CONCLUSIONS: Patients with persistent oligoJIA taking methotrexate are at least as likely to enter remission as patients with extended oligo JIA or polyarticular JIA. Patients with extended oligoJIA achieved JADAS remission significantly later. Within 2 years, almost half of the patients with persistent oligoJIA achieved JADAS-minimal disease activity.

Quality of life in localised malignant melanoma.

BACKGROUND: The incidence of melanoma is still increasing in fair-skinned populations. At least 80% of patients have localised disease and expect a 5-year relative survival of >90%. PATIENTS AND METHODS: In 2003-2004, disease-free patients with localised melanoma were recruited from the Munich Cancer Registry to answer quality-of-life (QoL) questionnaires 2 years after treatment. RESULTS: A response rate of 72% was achieved from a total of 1085 distributed questionnaires. Hundred and seventeen questionnaires had to be excluded because of updated information about secondary tumour and progression events. Thus, questionnaires from 664 patients were evaluated. QoL scores in melanoma patients were essentially similar to those of a general population. Differences were detected between women and men concerning emotional and sexual functioning. Age and number of comorbidities were the strongest factors influencing most all aspects of QoL. Fifty percent of patients referred to deficits in communication with their doctors. CONCLUSIONS: Patients who overcome melanoma do not necessarily have a reduced QoL. Strategies used by these melanoma patients resulted in similar levels of coping as previous studies in comparable general populations. Nevertheless, doctor-patient communication was correlated with emotional and social functioning and should be emphasised in treatment and care of melanoma patients.

Selenium status in term and preterm infants during the first months of life.

OBJECTIVE: We hypothesized that very low birth weight (VLBW) infants have reduced serum and red blood cell (RBC) selenium (Se) at birth, which decrease further with current nutrition and are associated with chronic lung disease and septicaemia. DESIGN: We studied Se intake, concentration in serum and RBCs and glutathione peroxidase (GSH-Px) activity in preterm and term infants from birth until 16 weeks. Data are mean+/-standard deviation (s.d.). SETTING: Seventy-two preterm infants in two groups, born in Berlin, gestational age 26+0/30+0 weeks, birth weight 845/1270 g, with low Se intake (2.2+/-0.8/2.5+/-1.2 microg/kg/day), and 55 term infants, gestational age 39+1 weeks, birth weight 3160 g, born in Venezuela (high Se intake: 29+/-8 microg/day). RESULTS: A balance study in 10 preterm infants showed that Se is well absorbed from human milk (77+/-9%). Serum concentration was higher in term (142.0+/-40.0 microg/l) than in preterm infants (17.8+/-8.1/19.9+/-2.2 microg/l) at 4/7 weeks. Serum and RBC concentration of Se declined in all infants, low values in preterm infants did not correlate with chronic lung disease and septicaemia. GSH-Px activity in RBCs remained stable until 6 weeks of age in all infants and was not correlated with Se in RBCs. CONCLUSIONS: Se concentration in serum decreases during the first weeks of life and depends on intake. GSH-Px activity is not useful as a marker for Se status in infants up to 16 weeks after birth.

Increased fear learning, spatial learning as well as neophobia in Rgs2-/- mice.

Anxiety disorders result from a complex interplay of genetic and environmental factors such as stress. On the level of cellular signaling, regulator of G protein signaling 2 (Rgs2) has been implicated in human and rodent anxiety. However, there is limited knowledge about the role of Rgs2 in fear learning and reactivity to stress. In this study, Rgs2-/- mice showed increased fear learning, male mice displayed increased contextual and cued fear learning, while females showed selectively enhanced cued fear learning. Male Rgs2-/- mice displayed increased long-term-contextual fear memory, but increased cued fear extinction. Learning in spatial non-aversive paradigms was also increased in Rgs2-/- mice. Female, but not male mice show increased spatial learning in the Barnes maze, while male mice showed enhanced place preference in the IntelliCage, rendering enhanced cognitive function non-specific for aversive stimuli. Consistent with the previous results, Rgs2 deletion resulted in increased innate anxiety, including neophobic behavior expressed as hypolocomotion, in three different tests based on the approach-avoidance conflict. Acute electric foot shock stress provoked hypolocomotion in several exploration-based tests, suggesting fear generalization in both genotypes. Rgs2 deletion was associated with reduced monoaminergic neurotransmitter levels in the hippocampus and prefrontal cortex and disturbed corresponding GPCR expression of the adrenergic, serotonergic, dopaminergic and neuropeptide Y system. Taken together, Rgs2 deletion promotes improved cognitive function as well as increased anxiety-like behavior, but has no effect on acute stress reactivity. These effects may be related to the observed disruption of the monoaminergic systems.

A functional genetic variation of SLC6A2 repressor hsa-miR-579-3p upregulates sympathetic noradrenergic processes of fear and anxiety.

Increased sympathetic noradrenergic signaling is crucially involved in fear and anxiety as defensive states. MicroRNAs regulate dynamic gene expression during synaptic plasticity and genetic variation of microRNAs modulating noradrenaline transporter gene (SLC6A2) expression may thus lead to altered central and peripheral processing of fear and anxiety. In silico prediction of microRNA regulation of SLC6A2 was confirmed by luciferase reporter assays and identified hsa-miR-579-3p as a regulating microRNA. The minor (T)-allele of rs2910931 (MAFcases = 0.431, MAFcontrols = 0.368) upstream of MIR579 was associated with panic disorder in patients (pallelic = 0.004, ncases = 506, ncontrols = 506) and with higher trait anxiety in healthy individuals (pASI = 0.029, pACQ = 0.047, n = 3112). Compared to the major (A)-allele, increased promoter activity was observed in luciferase reporter assays in vitro suggesting more effective MIR579 expression and SLC6A2 repression in vivo (p = 0.041). Healthy individuals carrying at least one (T)-allele showed a brain activation pattern suggesting increased defensive responding and sympathetic noradrenergic activation in midbrain and limbic areas during the extinction of conditioned fear. Panic disorder patients carrying two (T)-alleles showed elevated heart rates in an anxiety-provoking behavioral avoidance test (F(2, 270) = 5.47, p = 0.005). Fine-tuning of noradrenaline homeostasis by a MIR579 genetic variation modulated central and peripheral sympathetic noradrenergic activation during fear processing and anxiety. This study opens new perspectives on the role of microRNAs in the etiopathogenesis of anxiety disorders, particularly their cardiovascular symptoms and comorbidities.

Antibody recognition imaging by force microscopy.

We have developed a method that combines dynamic force microscopy with the simultaneous molecular recognition of an antigen by an antibody, during imaging. A magnetically oscillated atomic force microscopy tip carrying a tethered antibody was scanned over a surface to which lysozyme was bound. By oscillating the probe at an amplitude of only a few nanometers, the antibody was kept in close proximity to the surface, allowing fast and efficient antigen recognition and gentle interaction between tip and sample. Antigenic sites were evident from reduction of the oscillation amplitude, as a result of antibody-antigen recognition during the lateral scan. Lysozyme molecules bound to the surface were recognized by the antibody on the scanning tip with a few nanometers lateral resolution. In principle, any ligand can be tethered to the tip; thus, this technique could potentially be used for nanometer-scale epitope mapping of biomolecules and localizing receptor sites during biological processes.

Lead contamination and associated disease in captive and reintroduced red kites Milvus milvus in England.

Since 1989, a red kite Milvus milvus reintroduction programme has been underway in the United Kingdom, with 4-6 week old nestlings brought into captivity and held for 6-8 weeks before reintroduction. As scavengers, red kites may consume unretrieved game, and ingest shot or lead (Pb) fragments in their prey's flesh. We evaluated exposure to Pb in captive and wild red kites by taking blood samples from 125 captive young red kites prior to release, through analysing 264 pellets (regurgitated by wild birds) collected from under a roost site, and analysing Pb concentrations in livers and/or bones of 87 red kites found dead between 1995 and 2003. Lead isotope analyses of livers were also conducted in an effort to identify Pb exposure routes. Forty-six (36.8%) kites sampled prior to release had elevated blood Pb concentrations (201-3340 microg l(-1)). The source of this Pb was probably small fragments of lead ammunition in the carcasses of birds or mammals either fed to the nestlings by their parents or, more likely, subsequently whilst in captivity. Once released, kites were also exposed to lead shot in their food, and a minimum of 1.5-2.3% of regurgitated pellets contained Pb gunshot. Seven of 44 red kites found dead or that were captured sick and died within a few days had elevated (>6 mg kg(-1) dry weight [d.w.]) liver Pb concentrations, and six of these (14%) had concentrations of >15 mg kg(-1) d.w., compatible with fatal Pb poisoning. Post-mortem analyses indicated that two of these birds had died of other causes (poisoning by rodenticide and a banned agricultural pesticide); the remaining four (9%) probably died of Pb poisoning. Bone samples from 86 red kites showed a skewed distribution of Pb concentration, and 18 samples (21%) had Pb concentrations >20 mg kg(-1) d.w., indicating elevated exposure to Pb at some stage in the birds' life. Lead isotopic signatures (Pb (208/206); Pb (206/207)) in liver samples of the majority of kites were compatible with those found in lead shot extracted from regurgitated pellets. Lead isotope ratios found in the livers of kites with very low Pb concentrations were distinct from UK petrol Pb isotopic signatures, indicating that birds were exposed to little residual petrol Pb. We conclude that the primary source of Pb to which red kites are exposed is lead ammunition (shotgun pellets or rifle bullets), or fragments thereof, in their food sources; in some cases exposure appears sufficient to be fatal. We make recommendations to reduce Pb poisoning in both captive and wild red kites and other scavenging species.

The potential for kelp manufacture to lead to arsenic pollution of remote Scottish islands.

Burning seaweed to produce kelp, valued for its high potash and soda content, was formerly a significant industry in remote coastal areas of Scotland and elsewhere. Given the high concentrations of arsenic in seaweeds, up to 100 mg kg(-1), this study investigates the possibility that the kelp industry caused arsenic contamination of these pristine environments. A series of laboratory-scale seaweed burning experiments was conducted, and analysis of the products using HPLC ICP-MS shows that at least 40% of the arsenic originally in the seaweed could have been released into the fumes. The hypothesis that the burning process transforms arsenic from low toxicity arsenosugars in the original seaweeds (Fucus vesiculosus and Laminaria digitata) to highly toxic inorganic forms, predominantly arsenate, is consistent with As speciation analysis results. A field study conducted on Westray, Orkney, once a major centre for kelp production, shows that elevated arsenic levels (10.7+/-3.0 mg kg(-1), compared to background levels of 1.7+/-0.2 mg kg(-1)) persist in soils in the immediate vicinity of the kelp burning pits. A model combining results from the burning experiments with data from historical records demonstrates the potential for arsenic deposition of 47 g ha(-1) year(-1) on land adjacent to the main kelp burning location on Westray, and for arsenic concentrations exceeding current UK soil guideline values during the 50 year period of peak kelp production.

Assessing rare earth elements in quartz rich geological samples.

Sodium peroxide (Na2O2) fusion coupled to Inductively Coupled Plasma Tandem Mass Spectrometry (ICP-MS/MS) measurements was used to rapidly screen quartz-rich geological samples for rare earth element (REE) content. The method accuracy was checked with a geological reference material and Instrumental Neutron Activation Analysis (INAA) measurements. The used mass-mode combinations presented accurate results (only exception being (157)Gd in He gas mode) with recovery of the geological reference material QLO-1 between 80% and 98% (lower values for Lu, Nd and Sm) and in general comparable to INAA measurements. Low limits of detection for all elements were achieved, generally below 10 pg g(-1), as well as measurement repeatability below 15%. Overall, the Na2O2/ICP-MS/MS method proved to be a suitable lab-based method to quickly and accurately screen rock samples originating from quartz-rich geological areas for rare earth element content; particularly useful if checking commercial viability.

The mechanisms of detoxification of As(III), dimethylarsinic acid (DMA) and As(V) in the microalga Chlorella vulgaris.

The response of Chlorella vulgaris when challenged by As(III), As(V) and dimethylarsinic acid (DMA) was assessed through experiments on adsorption, efflux and speciation of arsenic (reduction, oxidation, methylation and chelation with glutathione/phytochelatin [GSH/PC]). Our study indicates that at high concentrations of phosphate (1.62mM of HPO4(2-)), upon exposure to As(V), cells are able to shift towards methylation of As(V) rather than PC formation. Treatment with As(V) caused a moderate decrease in intracellular pH and a strong increase in the concentration of free thiols (GSH). Passive surface adsorption was found to be negligible for living cells exposed to DMA and As(V). However, adsorption of As(III) was observed to be an active process in C. vulgaris, because it did not show saturation at any of the exposure periods. Chelation of As(III) with GS/PC and to a lesser extent hGS/hPC is a major detoxification mechanism employed by C. vulgaris cells when exposed to As(III). The increase of bound As-GS/PC complexes was found to be strongly related to an increase in concentration of As(III) in media. C. vulgaris cells did not produce any As-GS/PC complex when exposed to As(V). This may indicate that a reduction step is needed for As(V) complexation with GSH/PC. C. vulgaris cells formed DMAS(V)-GS upon exposure to DMA independent of the exposure period. As(III) triggers the formation of arsenic complexes with PC and homophytochelatins (hPC) and their compartmentalisation to vacuoles. A conceptual model was devised to explain the mechanisms involving ABCC1/2 transport. The potential of C. vulgaris to bio-remediate arsenic from water appeared to be highly selective and effective without the potential hazard of reducing As(V) to As(III), which is more toxic to humans.

Sub-lethal cadmium exposure increases phytochelatin concentrations in the aquatic snail Lymnaea stagnalis.

Phytochelatins are metal-binding metabolites found in almost all plant species and some animal groups, including nematodes and annelids, where they can play an important role in detoxifying metals such as cadmium. Species from several other taxa contain a phytochelatin synthase (PCS) gene orthologue, including molluscs, indicating they may have the potential to synthesize phytochelatins. However, the presence of a gene alone does not demonstrate that it plays a functional role in metal detoxification. In the present study, we show that the aquatic snail Lymnaea stagnalis produced both penta- and heptapeptide phytochelatins (i.e. phytochelatin-2 and phytochelatin-3), and their levels increased in response to sub-lethal levels of cadmium.

Accuracy of a method based on atomic absorption spectrometry to determine inorganic arsenic in food: Outcome of the collaborative trial IMEP-41.

A collaborative trial was conducted to determine the performance characteristics of an analytical method for the quantification of inorganic arsenic (iAs) in food. The method is based on (i) solubilisation of the protein matrix with concentrated hydrochloric acid to denature proteins and allow the release of all arsenic species into solution, and (ii) subsequent extraction of the inorganic arsenic present in the acid medium using chloroform followed by back-extraction to acidic medium. The final detection and quantification is done by flow injection hydride generation atomic absorption spectrometry (FI-HG-AAS). The seven test items used in this exercise were reference materials covering a broad range of matrices: mussels, cabbage, seaweed (hijiki), fish protein, rice, wheat, mushrooms, with concentrations ranging from 0.074 to 7.55mgkg(-1). The relative standard deviation for repeatability (RSDr) ranged from 4.1 to 10.3%, while the relative standard deviation for reproducibility (RSDR) ranged from 6.1 to 22.8%.

Trends in surgery and outcomes of squamous cell vulvar cancer patients over a 16-year period (1998-2013): a population-based analysis.

PURPOSE: The objective was to identify trends in surgery and the outcomes of squamous cell vulvar cancer in a population-based setting. METHODS: A total of 1113 patients with squamous cell vulvar cancer diagnosed between 1998 and 2013 in the catchment area of the Munich Cancer Registry (population approximately 4.6 million) were analysed. Trends in prognostic factors and treatment were examined by comparing patients diagnosed between 1998 and 2008 with those diagnosed between 2009 and 2013. Cumulative incidence was used to calculate time to local (LR) and lymph node recurrence (LNR). Survival was analysed by the Kaplan-Meier method, calculation of relative survival (RS), and a Cox model. RESULTS: The high median age at diagnosis of 75 years did not change significantly over time. In addition, no changes in the subsite of tumour or grading were noted. A decrease in patients undergoing complete vulvectomy from 27.7 to 17.8 % (p < 0.001) as well as an increase in the use of sentinel lymph node biopsy from 11.4 to 39.1 % (p < 0.001) was observed. However, time to LR (from 19 to 19 %) and time to LNR (from 9 to 9 %) as well as 5-year overall survival (from 55 to 55 %) and RS (from 66 to 63 %) were not significantly altered. After adjustment for prognostic factors, less radical locoregional surgery had no influence on survival. CONCLUSION: Less radical locoregional surgery in vulvar cancer is increasingly implemented. Locoregional recurrence and survival have not been affected by these changes and are likely accompanied by an improvement in quality of life.

High-molecular-weight kininogen is a binding protein for tissue prokallikrein.

Human tissue prokallikrein, a zymogen of the kallikrein-kinin system, circulates in plasma bound to neutrophils. Because plasma kininogens contribute to the assembly of kinin-generating components on blood cells, these proteins were assessed for their ability to complex the kallikrein precursor. Using ligand blot and direct binding assays, biotinylated prokallikrein was found to bind only to high-molecular-weight kininogen and not to the low-molecular-weight form. The interaction was specific, reversible, and saturable yielding an estimated dissociation constant K(D)=690 nM and a 1:1 stoichiometry. Specific kininogen binding of tissue prokallikrein also occurred at physiological plasma protein concentrations. These results provide the first evidence for a novel function of high-molecular-weight kininogen as a binding protein for tissue prokallikrein that could serve to localize the kallikrein precursor on the neutrophil surface.