Reduction in advanced breast cancer after introduction of a mammography screening program in Tyrol/Austria.

BACKGROUND: We analysed all female breast cancer (BC) cases in Tyrol/Austria regarding the shift in cancer characteristics, especially the shift in advanced BC, for the group exposed to screening as compared to the group unexposed to screening. METHODS: The analysis was based on all BC cases diagnosed in women aged 40-69 years, resident in Tyrol, and diagnosed between 2009 and 2013. The data were linked to the Tyrolean mammography screening programme database to classify BC cases as "exposed to screening" or "unexposed to screening". Age-adjusted relative risks (RR) were estimated by relating the exposed to the unexposed group. RESULTS: In a total of about 145,000 women aged 40-69 years living in Tyrol during the study period, 1475 invasive BC cases were registered. We estimated an age-adjusted relative risk (RR) for tumour size ≥ 21 mm of 0.72 (95% confidence interval (CI) 0.60 to 0.86), for metastatic BC of 0.27 (95% CI 0.17 to 0.46) and for advanced BC of 0.83 (95% CI 0.71 to 0.96), each comparing those exposed to those unexposed to screening, respectively. CONCLUSION: In our population-based registry analysis we observed that participation in the mammography screening programme in Tyrol is associated with a 28% decrease in risk for BC cases with tumour size ≥ 21 mm and a 17% decrease in risk for advanced BC. We therefore expect the Tyrolean mammography programme to show a reduction in BC mortality.

Quantitation of hindered amine light stabilizers in plastic materials by high performance liquid chromatography and mass spectrometric detection using electrospray ionization and atmospheric pressure photoionization.

In this work new high performance liquid chromatographic methods in combination with mass spectrometry have been developed for the quantitation of hindered amine light stabilizers (HALS) which are commonly used as monomeric and oligomeric species for stabilization of plastic materials. These analytes are difficult to separate under traditional reversed phase conditions. In the present study new silica-based pH stable reversed phases that had become available recently were investigated for HALS analysis, and turned out to be well suited employing mobile phases at a pH of around 11 adjusted by addition of ammonia. Detection was done by mass spectrometry employing both time-of-flight and triple quadrupole mass analyzers. The performance of electrospray ionization (ESI) as well as atmospheric pressure photoionization (APPI) was investigated and compared. Despite the high pH of the mobile phase, an excellent ionization could be obtained in the positive ion mode. ESI provided slightly lower limits of quantitation (on average a factor of 2) in comparison with APPI. The method allowed the quantitation of a range of different HALS down to 0.05-0.005% (depending on the HALS) in polymeric materials. Sample preparation consisted in dissolving the sample in toluene and precipitation of the polymer with acetone. The procedure can be routinely applied to aging tests of plastic materials in order to predict the lifetime of plastic components.

Studies on the emission behavior of polypropylene by gas chromatography/mass spectrometry with static headspace or thermodesorption.

Emissions from polypropylene (PP) may cause undesired smell, be harmful, or lead to so-called fogging which prohibits its use for car interiors. Thus, qualitative as well as quantitative emission studies are necessary. Thermodesorption (TDS) and static headspace (sHS) with subsequent GC-MS analysis are two powerful tools for analyzing the emission behavior of polymers with a minimum of sample handling. In this work we investigated the emission behavior of PP with TDS and sHS coupled to GC-MS paying special attention to quantitative considerations and to the relevance of emitted substances for fogging phenomena. After extraction for 30min and incubation for 2h, TDS-GC-MS and sHS-GC-MS results were satisfyingly repeatable (with relative standard deviations up to 5%). TDS allowed to introduce substances up to higher boiling points into the GC-MS system, but required to control sample geometry, as emission depended rather on sample surface than on sample mass. In sHS, emission was governed by partitioning between the gas and the sample phase rather than by full evaporation of the analytes. Above a certain analyte-dependent amount, peak area became independent of the sample amount. However, if the sample amount was kept constant, peak areas of emitted substances showed a linear dependence upon concentration of volatiles. Therefore, accurate quantitation was still possible. Typically alkanes, alkenes and dialkenes dominate TDS-GC-MS and sHS-GC-MS chromatograms of PP. They only contributed to fogging if they had a chain length higher than C16. These substances were only detectable when TDS was used for sample introduction, but not with sHS. sHS-GC-MS is thus not useful for judging fogging behavior.

Capillary electrokinetic chromatography of insulin and related synthetic analogues.

With the implementation of recombinant DNA technology in the pharmaceutical industry, some synthetic insulins have been developed in order to improve the therapy of diabetes. These analogues differ only slightly in the amino acid sequence, therefore displaying a great challenge for analytical chemistry. Within the work presented in this paper, capillary zone electrophoresis (CZE), micellar electrokinetic chromatography (MEKC) with sodium dodecylsulphate (SDS) as micelle-forming agent, and microemulsion electrokinetic chromatography (MEEKC) with microemulsions consisting of SDS, n-octane and 1-butanol were investigated for the separation of human insulin and five synthetic analogues. Best results were achieved with a solvent-modified MEKC system consisting of 100mM sodium dodecyl sulphate and 15% acetonitrile in 10mM borate buffer (pH 9.2). A similar system based on perfluorooctanoic acid as micelle-forming agent in ammonium acetate (pH 9.2) was successfully employed for the hyphenation with a quadrupole/time-of-flight mass spectrometer via a sheath-flow interface. In this case, detection limits at 10mg/L could be achieved.

[Pathological examination of breast biopsy specimens]. / Pathologische Aufarbeitung von Mammabiopsaten.

No differences for long-term disease free survival could be found between breast conserving surgery and mastectomy. Most importantly is the fact that this therapy presents a significantly higher risk for local recurrence. The characterisation of this risk is one of the most important things to do. These findings result in a widespread change in treatment of breast cancer patients. Consequently an increase in interdisciplinary working between radiologists, surgeons and pathologists could be found. Histological examinations are necessary for diagnosis and exactly evaluation of the tumor extension. Microscopic evaluation of the resection margin is of most important interest, because there is a direct connection between local recurrence and tumor infiltration of the resection margin. We performed our investigations by the use of a standardized complete embedding method with the possibility of three-dimensional reconstruction, on a cohort of 280 patients. Additionally this method allowed the detection of all relevant findings on one hand and on the other hand an evaluation of all resection margins. Our results showed a breast conserving therapy including tumor free margins was performed in 67% of the patients. But there was a second resection necessary in 57% of the cases. An extensive tumor distribution as the detection of multifocal tumor spread was the reason for mastectomy in 33%. Our findings point out the necessarily of the histological examination in the line of the complete embedding method of the breast biopsy material in order to analyse the tumor including resection margin evaluation.

[Sonographically guided core needle biopsy of the breast: technique, accuracy and indications]. / Ultraschallgezielte Stanzbiopsie der Mamma: Technik, Ergebnisse, Indikationen.

PURPOSE: The purpose of this retrospective analysis was to assess the diagnostic accuracy and complication rate of sonographically guided core needle biopsy in palpable breast masses, mammographically detected nonpalpable lesions, and sonographically detected clinically and mammographically occult lesions. PATIENTS AND METHODS: Sonographically guided core needle biopsy was performed in 590 lesions in 572 patients, by using an automated biopsy gun with a 14-gauge large core needle and a coaxial system. Core needle biopsy results were compared with surgical biopsy in 265 cases. 325 lesions with benign histologic diagnoses were followed up for at least 18 months. RESULTS: 234 carcinomas and 356 benign abnormalities were found in the 572 patients. Core needle biopsy reached a sensitivity of 98.7% at a specificity of 99.7%. Underestimation rates for lesions initially diagnosed as DCIS and for lesions initially diagnosed as ADH were 3/10 and 6/14, respectively. Of three false-negative results, two were immediately recognized, and one was identified at follow-up. Serious bleeding occurred in one patient (0.2% complication rate). CONCLUSIONS: This report confirms that sonographically guided large core needle biopsy is a safe, reliable and cost-effective method for the assessment of both palpable and nonpalpable, mammographically and sonographically detected breast abnormalities.

Multiclass/multiresidue method for monitoring widely applied plant protecting agents in air during field dispersion work.

A multiclass/multiresidue method for surveying the uptake of plant protecting chemicals by inhalation during field spraying work is described. Eleven nowadays mainly dispersed compounds, which cover a wide range of chemical properties, are analysed in air with personal active sampling and in one single analytical run. This has the advantage, that one basic method only needs to be implemented, calibrated and validated in a laboratory to perform varying monitoring tasks without changing the method itself. Samples were taken with Tenax sorbent tubes operated to collect the active compounds simultaneously in the vapour state, in aerosol state or bound to particles. The procedure consists of four unit operations only: sampling, elution, dilution and HPLC measurement, and is described in SOP-format. The limits of quantification, calculated as method detection limits, were between 1 and 9 microg m(-3) based on 1 m3 air volume sampled (8 h). Method performance was characterised by way of generated test atmospheres and field spraying trials.

Determination of carbohydrates by capillary electrophoresis with electrospray-mass spectrometric detection.

A method for the determination of underivatized carbohydrates using capillary electrophoresis (CE) with detection by electrospray ionization-mass spectrometry (ESI-MS) presented. Highly alkaline carrier electrolytes based on volatile organic bases like is diethylamine (DEA) combined with MS detection in the negativ-ion mode proved to be the optimum solution for the separation and detection of these analytes. Optimization of the carrier electrolyte composition has been performed with respect to its pH, ionic strength as well as the addition of an organic modifier. The influence of the DEA concentration in the sheath liquid on parameters like peak shapes or signal-to-noise (S/N) ratios was also investigated. Limits of detection (LOD) were in the range of 0.5-3.0 mgL(-1) and calibration was linear over an order of magnitude for almost all solutes investigated. Finally, the applicability of this method for the analysis of real samples was demonstrated with wine samples.

[Radiation exposure in single slice and multi-slice spiral CT (a phantom study)]. / Untersuchungen zur Strahlenexposition bei der Einzelschicht- und Mehrschicht-Spiral-CT (eine Phantom-Studie).

PURPOSE: The purpose of study was to compare patient dose applying singleslice- and multislice-spiral CT. METHODS: The examinations were performed with a singleslice-spiral CT (Highspeed Advantage; GE Medical Systems; Milwaukee, USA) and with a multislice CT systems (LightSpeed QX/i GE Medical Systems; Milwaukee, USA). For the determination of the radiation exposure (absorbed dose) a selection of most executed protocols (thorax-helical, abdomen-helical, petrous bone-axial, head-axial) were simulated using an Alderson Rando Phantom. The dose was determined by means of lithiumfluorid-thermoluminiscence dosimeters (TLD-GR 200). RESULTS: For thorax and abdomen protocols higher energy dose values could be found using a multislice CT. On the average the energy dose values were increased by 2.6 on an average in relation to single slice spiral CT. The energy dose values of the multisclice CT using head protocols could be reduced by 30% in relation to single slice spiral CT due to suitable parameter selections. The energy dose applying a petrous bone protocol resulted in an average increase by a factor 1.5 using a multislice CT. CONCLUSION: Using the new multislice CT technique protocol strategies must be optimized regarding the patient doses. Users can operate critically in the sense of the radiation protection only if they are aware of the occurring dose amounts to the patient.

Psychophysical aspects in medical illumination techniques.

The relation between image and visual perception of the human eye is an important point in digital imaging systems. Research aims should therefore pay attention to psychophysical aspects. Optimising of digital imaging systems can only be reached if the important final steps in the diagnostic process--visual perception and signal detection--are taken into account.

Separation of hydrophobic polymer additives by microemulsion electrokinetic chromatography.

Microemulsion electrokinetic chromatography (MEEKC) has been applied to the separation of some phenolic antioxidants [Irganox 1024, Irganox 1035, Irganox 1076, Irganox 1010, Irganox 1330, Irgafos 138, Irganox 168 and 2,6-di-tert.-butyl-4-methylphenol (BHT)]. Due to the extremely hydrophobic nature of these analytes, they could not be separated using standard MEEKC conditions and two alternative approaches were investigated. Using an acidic buffer (phosphate, pH 2.5) to effectively suppress the electroosmotic flow, the addition of 2-propanol to the aqueous phase of the microemulsion buffer to improve partitioning of the analytes, and a negative separation voltage, separation of five of the analytes in under 10 min was possible. The second approach, using a basic buffer (borate, pH 9.2) and a positive separation voltage resulted in complete resolution of all eight analytes. A mixed surfactant system comprising the anionic sodium dodecyl sulfate (SDS) and neutral Brij 35 was used to reduce the overall charge and with it the mobility of the droplets, and hence the separation time. Using an optimised MEEKC buffer consisting of 2.25% (w/w) SDS, 0.75% (w/w) Brij 35, 0.8% (w/w) n-octane, 6.6% (w/w) 1-butanol, 25% (w/w) 2-propanol and 64.6% (w/w) 10 mM borate buffer (pH 9.2) the eight target analytes were baseline separated in under 25 min. For these analytes, MEEKC was found to be superior to micellar electrokinetic chromatography in every respect. Specifically, the solubility of the analytes was better, the selectivity was more favourable, the analysis time was shorter and the separation efficiency was up to 72% higher when using the MEEKC method. Detection limits from 5.4 to 26 microg/ml were obtained and the calibration plot was linear over more than one order of magnitude. The optimised method could be applied to the determination of Irganox 1330 and Irganox 1010 in polypropylene.

Determination of quaternary alkylammonium compounds by capillary zone electrophoresis and indirect UV detection as a real alternative to ion chromatography with suppressed conductivity detection.

A capillary electrophoretic (CE) method for the determination of residual mid-chain alkyltrimethylammonium compounds in the pharmaceutical product Welchol (an alkylated, crosslinked polyallylamine) was developed, validated and compared with the existing ion chromatographic (IC) method with suppressed conductivity detection. Excellent reproducibilities of migration times (RSD<0.5% within a series of 55 sample injections) and relative peak areas (RSD<2%) make the method suitable for quality control as a real alternative to IC. Limits of quantification of 0.01% w/w of each impurity in the active substance were achieved. Buffer systems for indirect UV detection based on creatinine as visualization reagent with different inorganic and organic acids (phosphoric, sulfuric, formic, acetic, oxalic and citric acid) and their effect on selectivity to ten quaternary ammonium compounds were studied. Selectivity changes were observed for the di- and trivalent analytes depending on the buffer applied. Also, the influence of acetonitrile, methanol, 1,4-dioxane and tetrahydrofuran on selectivity was investigated. In addition, CE-MS experiments were carried out in order to identify several impurities in the product.

Lonene-coated sulfonated silica as a packing material in the packed-capillary mode of electrochromatography.

An aliphatic ionene (2-10-ionene) has been selected as a modifier to prepare a novel polymer-coated packing material for capillary electrochromatography. The packing material was produced by dynamical modification of a commercially available sulfonated silica Exsil-100 SCX. Strong ion-exchange interactions in the capillary packed with ionene-modified sulfonated silica have been demonstrated by the example of the retention of p-aminobenzoic acid. The total calculated anion-exchange capacity of the sorbent in the capillary was about 4 x 10(-9) mol. A fast separation (about 15 min) of several aromatic acids was achieved with the packing material. The highest number of theoretical plates obtained was about 120,000. Limits of detection of the aromatic acids were 2-5 microg/ml. The advantages and lacks of the approach are discussed briefly.

Multisegmental pneumatocysts of the lumbar spine mimic osteolytic lesions.

Circumscribed radiolucencies within the vertebral bones can be due to a variety of changes including benign and malignant tumours or tumour-like lesions. Radiolucencies due to degenerative intraosseous pneumatocyst are very uncommon but have to be taken into the differential diagnosis in well-circumscribed lytic lesions of the vertebral bodies. We describe the first case of multisegmental pneumatocysts in the lumbar spine mimicking osteolytic lesions. On computed tomography, the air-equivalent attenuation values of the lesions and the close vicinity to the degenerated vertebral endplates with vacuum phenomenon led to the correct diagnosis.

Radial nerve palsy associated with humeral shaft fracture: evaluation with US--initial experience.

PURPOSE: To determine the feasibility of using ultrasonography (US) for evaluation of a radial nerve injury associated with humeral shaft fracture. MATERIALS AND METHODS: In a prospective study, 11 consecutive patients with sensorimotor radial deficiency after distal humeral fracture were evaluated with conventional radiography, US, electroneurography, and electromyography. Surgical repair of the fracture and nerve inspection were performed in five patients. The remaining six patients were successfully treated conservatively. The US appearance of the radial nerve was studied in 10 healthy volunteers and in the noninjured arm of the 11 patients for comparison. RESULTS: In five patients, US findings of a severely damaged radial nerve were confirmed at surgical nerve inspection. In one patient, the nerve was entrapped between fragments. One patient had a complete nerve dissection, one had a lacerated nerve from a loose compression plate, and one had a nerve riding on the edge of a bone fragment. In the fifth patient who underwent surgical inspection, the nerve was buried in the callus. In the six patients treated conservatively, US showed continuity of the nerve. CONCLUSION: US may be useful for accurate evaluation of the radial nerve in patients with nerve palsy associated with humeral shaft fracture.

Identification of unknown degradation products in a new cholesterol-reducing drug by ion-chromatography coupled to mass spectrometry.

The combination of suppressed and non-suppressed cation-exchange chromatography with electrospray ionization mass spectrometry was demonstrated for the structural elucidation of unknown by-products (mostly quaternary ammonium compounds) in a new cholesterol-reducing drug. The suppressed mode using methanesulfonic acid and acetonitrile turned out to be unsuitable because of regenerant (tetrabutylammonium hydroxide) passing through the membrane of the suppressor into the eluent which led to a significant increase of spectral background in the mass spectrometer. Employing a mobile phase consisting of 200 mM formic acid and 60% (v/v) acetonitrile, the separation and detection of 8 unknown compounds was possible in the non-suppressed mode. The three most prominent compounds were selected for structural elucidation utilizing collision induced dissociation experiments. In a series of experiments the fragmentation behavior was investigated for different fragmentation voltages finally leading to structure proposals. Using gas chromatography hyphenated with mass spectrometry, additional information for the structure of the unknowns was collected and a possible way of their formation was proposed.

Fast separation of pyrimidine derivatives by capillary electrochromatography on ion-exchange/reversed-phase mixed-mode stationary phases.

This work describes the use of mixed-mode stationary phases which exhibit both strong ion-exchange (either cation-exchange, SCX, or anion-exchange, SAX) and reversed-phase chromatographic characteristics in capillary electrochromatographic separations of pyrimidine derivatives. Different packing materials, namely C6, SCX/C6 and SAX/C6, were compared and the influence of the composition of the carrier electrolyte (concentration of acetonitrile and pH) on the retention behavior of the selected solutes was investigated. A separation of all eight pyrimidine derivatives could be obtained on a 6.5 cm column packed with the SAX/C6 stationary phase in less than 3 min, with good peak shapes and efficiencies in the range 39,000 to 81,000 plates per meter.

Determination of drug residues in water by the combination of liquid chromatography or capillary electrophoresis with electrospray mass spectrometry.

Methods for the determination of drug residues in water have been developed based on the combination of liquid chromatography (LC) or capillary electrophoresis (CE) with mass spectrometry (MS). For HPLC-MS two types of interfaces (pneumatically assisted electrospray ionization interface or an atmospheric pressure chemical ionization interface, respectively) were employed and compared in terms of detection limits. 2 mM Ammonium acetate at pH 5.5 and a methanol gradient was used for the HPLC-MS allowing the separation of a number of drugs such as paracetamol, clofibric acid, penicillin V, naproxen, bezafibrate, carbamazepine, diclofenac, ibuprofen and mefenamic acid. A 20 mM ammonium acetate solution, pH 5.1 was employed for the separation of clofibric acid, naproxen, bezafibrate, diclofenac, ibuprofen and mefenamic acid by CE-MS. Sample pretreatment was performed by solid-phase extraction (SPE) for HPLC-MS or by a combination of liquid-liquid extraction and SPE for CE-MS. The applicability of both the HPLC-MS and CE-MS method was demonstrated for several river water samples.

Monitoring of tumor microcirculation during fractionated radiation therapy in patients with rectal carcinoma: preliminary results and implications for therapy.

PURPOSE: To measure microcirculatory changes during chemoirradiation and to correlate perfusion index (PI) values with therapy outcome. MATERIALS AND METHODS: Perfusion data in 11 patients with cT3 (clinical staging, tumor invaded the perirectal tissue) rectal carcinoma who underwent preoperative chemoirradiation were analyzed. Perfusion data were acquired by using a T1 mapping sequence with a whole-body magnetic resonance (MR) imager. After contrast medium was intravenously infused at a constant rate, concentration-and-time curves were evaluated for arterial blood and tumor. All patients underwent MR imaging before and at constant intervals during chemoirradiation. Clinical stages before therapy were compared with surgical stages after therapy. RESULTS: Spatial and temporal resolution on dynamic T1 maps were sufficient to reveal changes in contrast medium accumulation in the tumor. Comparison of PI values and radiation dose showed a significant increase in the 1st (P: =.003) and 2nd weeks (P: =.01) of treatment; values subsequently returned to pretreatment levels or showed a renewed increase. High initial PI values correlated with greater lymph node downstaging (P: =.042). CONCLUSION: Dynamic T1 mapping provides a suitable tool for monitoring tumor microcirculation during chemoirradiation and offers the potential for individual optimization of therapeutic procedures. Furthermore, these results indicate that the PI map may serve as a prognostic factor.

Clinically and mammographically occult breast lesions: detection and classification with high-resolution sonography.

With recent significant advances in ultrasound technology, the potential of high-resolution sonography to improve the sensitivity of cancer diagnosis in women with dense breasts has become a matter of interest for breast imagers. To determine how often physician-performed high-resolution sonography can detect nonpalpable breast cancers that are not revealed by mammography, 8,970 women with breast density grades 2 through 4 underwent high-resolution sonography as an adjunct to mammography. All sonographically detected, clinically and mammographically occult breast lesions that were not simple cysts were prospectively classified into benign, indeterminate, or malignant categories. Diagnoses were confirmed by ultrasound-guided fine-needle aspiration, core-needle biopsy, or surgical biopsy. In 8,103 women with normal findings at mammography and physical examination, 32 cancers and 330 benign lesions were detected in 273 patients with sonography only. Eight additional cancers were found in 867 patients with a malignant (n = 5) or a benign (n = 3) palpable or mammographically detected index lesion. The overall prevalence of cancers detected with screening sonography was 0.41%, and the proportion of sonographically detected cancers to the total number of nonpalpable cancers was 22%. The mean size of invasive cancers detected only by sonography was 9.1 mm, and was not statistically different from the mean size of invasive cancers detected by mammography. The sensitivity of prospective sonographic classification for malignancy was 100%, and the specificity was 31%. In conclusion, the use of high-resolution sonography as an adjunct to mammography in women with dense breasts may lead to detection of a significant number of otherwise occult cancers that are no different in size from nonpalpable mammographically detected cancers. Prospective classification of these lesions based on sonographic characteristics resulted in an acceptable benign-to-malignant biopsy rate of 6.3:1.