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Wang Z.,Paul Scherrer Institute | Hauser N.,The Interdisciplinary Center | Singer G.,Institute of Pathology | Trippel M.,Institute of Pathology | And 4 more authors.
Nature Communications | Year: 2014

Microcalcifications can be indicative in the diagnosis of early breast cancer. Here we report a non-invasive diagnostic method that may potentially distinguish between different types of microcalcifications using X-ray phase-contrast imaging. Our approach exploits the complementary nature of the absorption and small-angle scattering signals of microcalcifications, obtained simultaneously with an X-ray grating interferometer on a conventional X-ray tube. We demonstrate that the new approach has 100% sensitivity and specificity when applied to phantom data, and we provide evidence of the solidity of the technique by showing its discrimination power when applied to fixed biopsies, to non-fixed tissue specimens and to fresh, whole-breast samples. The proposed method might be further developed to improve early breast cancer diagnosis and has the potential to increase the diagnostic accuracy and reduce the number of uncomfortable breast biopsies, or, in case of widespread microcalcifications, to select the biopsy site before intervention. © 2014 Macmillan Publishers Limited. All rights reserved.


Stampanoni M.,Paul Scherrer Institute | Stampanoni M.,ETH Zurich | Wang Z.,Paul Scherrer Institute | Thuring T.,Paul Scherrer Institute | And 7 more authors.
Investigative Radiology | Year: 2011

Objectives: Phase-contrast and scattering-based X-ray imaging are known to provide additional and complementary information to conventional, absorption-based methods, and therefore have the potential to play a crucial role in medical diagnostics. We report on the first mammographic investigation of 5 native, that is, freshly dissected, breasts carried out with a grating interferometer and a conventional X-ray tube source. Four patients in this study had histopathologically proven invasive breast cancer. One male patient, without the presence of any malignant formations within the resected breast, was included as a control specimen. MATERIALS AND METHODS:: We used a Talbot-Lau grating setup installed on a conventional, low-brilliance X-ray source; the interferometer operated at the fifth Talbot distance, at a tube voltage of 40 kVp with mean energy of 28 keV, and at a current of 25 mA. The device simultaneously recorded absorption, differential phase and small-angle scattering signals from the native breast tissue. These quantities were then combined into novel color-and high-frequency-enhanced radiographic images. Presurgical images (conventional mammography, ultrasonography, and magnetic resonance imaging) supported the findings and clinical relevance was verified. RESULTS:: Our approach yields complementary and otherwise inaccessible information on the electron density distribution and the small-angle scattering power of the sample at the microscopic scale. This information can be used to potentially answer clinically relevant, yet unresolved questions such as unequivocally discerning between malignant and premalignant changes and postoperative scars and distinguishing cancer-invaded regions within healthy tissue. CONCLUSIONS:: We present the first ex vivo images of fresh, native breast tissue obtained from mastectomy specimens using grating interferometry. This technique yields improved diagnostic capabilities when compared with conventional mammography, especially when discerning the type of malignant conversions and their breadth within normal breast tissue. These promising results advance us toward the ultimate goal, using grating interferometry in vivo on humans in a clinical setting. © 2011 by Lippincott Williams & Wilkins.


Schoepfer A.M.,University of Lausanne | Safroneeva E.,University of Bern | Bussmann C.,Viollier AG | Kuchen T.,University of Zürich | And 4 more authors.
Gastroenterology | Year: 2013

Background & Aims Development of strictures is a major concern for patients with eosinophilic esophagitis (EoE). At diagnosis, EoE can present with an inflammatory phenotype (characterized by whitish exudates, furrows, and edema), a stricturing phenotype (characterized by rings and stenosis), or a combination of these. Little is known about progression of stricture formation; we evaluated stricture development over time in the absence of treatment and investigated risk factors for stricture formation. Methods We performed a retrospective study using the Swiss EoE Database, collecting data on 200 patients with symptomatic EoE (153 men; mean age at diagnosis, 39 ± 15 years old). Stricture severity was graded based on the degree of difficulty associated with passing of the standard adult endoscope. Results The median delay in diagnosis of EoE was 6 years (interquartile range, 2-12 years). With increasing duration of delay in diagnosis, the prevalence of fibrotic features of EoE, based on endoscopy, increased from 46.5% (diagnostic delay, 0-2 years) to 87.5% (diagnostic delay, >20 years; P =.020). Similarly, the prevalence of esophageal strictures increased with duration of diagnostic delay, from 17.2% (diagnostic delay, 0-2 years) to 70.8% (diagnostic delay, >20 years; P <.001). Diagnostic delay was the only risk factor for strictures at the time of EoE diagnosis (odds ratio = 1.08; 95% confidence interval: 1.040-1.122; P <.001). Conclusions The prevalence of esophageal strictures correlates with the duration of untreated disease. These findings indicate the need to minimize delay in diagnosis of EoE. © 2013 by the AGA Institute.


Pediconi F.,University of Rome La Sapienza | Kubik-Huch R.,Kantonsspital Baden | Chilla B.,Kantonsspital Baden | Schwenke C.,SCO SSiS | Kinkel K.,Institute Of Radiologie
European Radiology | Year: 2013

Objective: To demonstrate non-inferiority of gadobutrol versus gadobenate dimeglumine by intra-individually comparing 0.1mmol/kg body weight doses for contrast-enhanced breast magnetic resonance imaging (MRI) and prospectively evaluating lesion detection and characterisation in a multicentre trial. Methods: Two identical breast MRI examinations were performed in 72 patients with biopsy-proven breast cancer, separated by 1-7days. Gadobutrol 1.0M or gadobenate 0.5M were administered in a randomised order. Lesion detection and characterisation were performed by two independent blinded readers. Lesion tracking, which compared on-site readings and histology from surgery or biopsy, was performed by a third reader. Differences in lesion detection and characterisation were compared between the two contrast agents. Results: Among 103 lesions, 96 were malignant and 7 were benign. No difference in lesion detection was identified between the contrast agents (82.33% for gadobutrol, 81.60% for gadobenate). Assessment of sensitivity in lesion characterisation and Breast Imaging Reporting and Data Systems showed no difference between gadobutrol (92.63%) and gadobenate (90.53%). Regarding morphology, there was more non-focal enhancement for gadobutrol than for gadobenate (P = 0.0057). Conclusion: Non-inferiority of gadobutrol compared with gadobenate was demonstrated for breast lesion detection and sensitivity in lesion characterisation in breast MRI. Key Points: • Contrast-enhanced magnetic resonance imaging is now widely used for breast problems. • Lesion detection in breast MRI differs according to the contrast agent. • Thus we compared gadobutrol 1M with gadobenate dimeglumine 0.5M. • Gadobutrol was non-inferior to gadobenate dimeglumine for detecting and characterising malignant lesions. © 2012 European Society of Radiology.


Knuesel P.R.,Kantonsspital Baden | Kubik R.A.,Kantonsspital Baden | Crook D.W.,Kantonsspital Baden | Eigenmann F.,Kantonsspital Baden | Froehlich J.M.,Kantonsspital Baden
European Journal of Radiology | Year: 2010

Purpose: To retrospectively compare the dynamic contrast enhancement of the small bowel segments with and without active Crohn's disease at 3D MR enterography (MRE). Materials and methods: Thirteen patients (five men, eight women; mean age 41.2 years; range 29-56) were imaged on a 1.5-T MR scanner (Sonata, Siemens Medical) with standard MR sequences after having ingested 1000 ml of a 3% mannitol solution. Subsequently, high resolution 3D gradient-echo (volumetric interpolated breath-hold examination = VIBE) data sets were obtained pre-contrast and 20-40 s, 60-80 s, and 120-140 s after i.v. Gd-DOTA administration (0.2 mmol/kg). Signal enhancement was measured on single slices both in normal and histologically confirmed (12/13) inflamed small bowel wall segments as well as in the aorta, the psoas muscle, and the background to calculate signal-to-noise (SNR) and contrast-to-noise ratios (CNR). Results: Small bowel wall enhancement was significantly higher (p < 0.05) in inflamed compared to normal segments at 20-40 s (SNR inflamed: 58.7 ± 33.8 vs normal: 36.0 ± 19.8; p = 0.048; CNR inflamed: 34.8 ± 23.4 vs normal: 16.3 ± 11.2; p = 0.017) and at 60-80 s (SNR: 60.3 ± 25.1 vs 41.9 ± 20.0; p = 0.049; CNR: 34.9 ± 15.1 vs 19.3 ± 13.2; p = 0.01) after i.v. contrast administration, respectively. Even at 120-140 s CNR was still increased in inflamed segments (33.7 ± 16.0 vs 18.1 ± 13.2; p = 0.04), while differences in SNR did not attain statistical significance (63.0 ± 26.2 vs 45.3 ± 23.3; p = 0.15). Conclusion: In active Crohn's disease, histologically confirmed inflamed small bowel wall segments demonstrate a significantly increased early uptake of gadolinium on 3D VIBE sequences compared to normal small bowel segments. © 2008 Elsevier Ireland Ltd. All rights reserved.


Loos M.,TU Munich | Quentmeier P.,TU Munich | Schuster T.,TU Munich | Nitsche U.,TU Munich | And 5 more authors.
Annals of Surgical Oncology | Year: 2013

Background: Preoperative radio(chemo)therapy (pR(C)T) significantly reduces the local recurrence risk and is therefore recommended in stage II/III rectal cancer. However, this multimodal treatment approach may be associated with late adverse effects. To determine the impact of pR(C)T on long-term anorectal, sexual, and urinary function, we performed a systematic review and meta-analysis. Methods: PubMed, Embase, and the Cochrane Library were systematically searched for studies reporting on long-term functional outcome after rectal cancer resection with pR(C)T. Only studies that reported anorectal, sexual, and/or urinary function after rectal cancer resection in TME-technique with pR(C)T were eligible for inclusion. Results: Twenty-five studies, including 6,548 patients, were identified. Methodological quality of the eligible studies was low. The majority of studies reported higher rates of anorectal (14/18 studies) and male sexual dysfunction (9/10 studies) after pR(C)T. Few studies examined female sexual dysfunction (n = 4). Meta-analysis revealed that stool incontinence occurred more often in irradiated patients (risk ratio (RR) = 1.67; 95 % confidence interval (CI), 1.36, 2.05; p < 0.0001) and manometric results were significantly worse after pR(C)T (mean resting pressures (weighted mean difference (WMD) = 15.04; 95 % CI, 0.77, 29.31; p = 0.04) and maximum squeeze pressures (WMD = 30.39; 95 % CI, 21.48, 39.3; p < 0.0001)). Meta-analysis of erectile dysfunction revealed no statistical significance (RR = 1.41; 95 % CI, 0.74, 2.72; p = 0.3). Six of eight studies and meta-analysis demonstrated no negative effect of pR(C)T on urinary function (RR = 1.05; 95 % CI, 0.67, 1.65; p = 0.82). Conclusions: Although quality of studies on long-term functional outcome is limited, current evidence demonstrates that pR(C)T negatively affects anorectal function after TME. © 2012 Society of Surgical Oncology.


BACKGROUND:: Combined spinal–epidural labor analgesia has gained popularity, but it is unclear whether this technique is associated with a higher incidence of nonreassuring fetal heart rate (FHR) tracings compared with epidural analgesia. Our meta-analysis aimed at comparing the incidence of nonreassuring FHR tracings between the 2 neuraxial techniques. METHODS:: Databases were searched to identify randomized controlled trials that compared the incidence of nonreassuring FHR tracings, as defined in the individual studies, after combined spinal–epidural versus epidural analgesia in laboring women. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using the random-effects model. We performed a subgroup analysis for studies using low-dose epidural bupivacaine concentrations (≤0.125%) for epidural analgesia. RESULTS:: Seventeen trials including 3947 parturients were retrieved that compared the 2 neuraxial techniques. All trials used intrathecal opioids in 1 study arm. The pooled effect estimate of low- and high-dose epidural bupivacaine studies together showed a significantly increased risk of nonreassuring FHR tracings with the combined technique (RR 1.31, 95% CI 1.02–1.67, P = .03, I = 18%). A subgroup analysis of 10 trials using low-dose epidural bupivacaine found a RR for nonreassuring FHR tracings between combined spinal–epidural and epidural analgesia of 1.12, 95% CI 0.93–1.34, P = .18. In a sensitivity analysis of those low-dose epidural bupivacaine studies that ensured blinding of the outcome assessor, the RR was 1.41, 95% CI 0.99–2.02, P = .06. CONCLUSIONS:: Combined spinal–epidural labor analgesia was associated with a higher risk of nonreassuring FHR tracings than epidural analgesia alone. In the subgroup analysis comparing combined spinal–epidural with low-dose epidural labor analgesia, the 95% CI contains a clinically significant difference between groups; moreover, the 95% CI overlaps with the 95% CI of the comparison of the combined low- and high-dose epidural techniques. Therefore, it cannot be concluded that there was no difference between combined spinal–epidural and low-dose epidural techniques. © 2016 International Anesthesia Research Society


BACKGROUND:: Hypotension remains a frequent complication of spinal anesthesia, increasing the risk of nausea and vomiting, altered mental status, and aspiration. The aim of this systematic review and meta-analysis was to determine whether 5-hydroxytryptamine3 (5-HT3) receptor antagonists, administered before the initiation of spinal anesthesia, mitigate hypotension. METHODS:: After a systematic literature search in various databases, randomized placebo-controlled double-blind trials studying the preventive effect of 5-HT3 receptor antagonists were included. A random-effects model was applied, risk ratio (RR, binary variables) or weighted mean difference (continuous variables) with 95% confidence intervals (CIs) were calculated. The primary outcome was the incidence of hypotension. RESULTS:: Seventeen trials (8 obstetric, 9 non-obstetric) reporting on 1604 patients were identified. Ondansetron in doses from 2 to 12 mg was studied in 12 trials. Prophylactic 5-HT3 administration significantly reduced the risk of hypotension in the combined analysis of 17 trials, RR 0.54 (95% CI 0.36–0.81, I = 79%). In obstetric trials, the RR was 0.52, 95% CI 0.30–0.88, I = 87% (number needed to treat 4). In non-obstetric studies, the 95% CIs were wide and included a clinically relevant reduction in the risk of hypotension (RR 0.50, 95% CI 0.22–1.16; I = 66%). Contour-enhanced funnel plots confirmed publication bias. Meta-regression showed a significant ondansetron dose response in non-obstetric patients (β = −0.355, P = .04). In the combined and in the obstetric-only analysis, the risk of bradycardia was significantly reduced as was the use of phenylephrine equivalents. CONCLUSIONS:: 5-HT3 antagonists are effective in reducing the incidence of hypotension and bradycardia; the effects are moderate and are only significant in the subgroup of patients undergoing cesarean delivery. The effects in the non-obstetric population are not significant. © 2016 International Anesthesia Research Society


Heesen M.,Kantonsspital Baden | Klimek M.,Erasmus Medical Center
Current Opinion in Anaesthesiology | Year: 2016

Purpose of review Nonobstetric anesthesia during pregnancy is challenging-not only for the anesthetist. Owing to the difficulties of ethical consent for randomized studies in this special patient group, the available evidence is quite low. Nevertheless, recently several guidelines for the management of pregnant patients undergoing nonobstetric anesthesia have been published. We review the current guidelines developed under the auspices of the Society of American Gastrointestinal Endoscopic Surgeons, guidelines for the management of difficult and failed tracheal intubation in obstetrics, as well as guidelines for the management of a pregnant trauma patient. Recent findings The algorithms for management of the difficult airway during pregnancy should be made available in every institution that cares for pregnant women. During laparoscopic surgery strict limitation of the pneumoperitoneal pressure to avoid maternal hypercapnia and fetal acidosis is strongly recommended. An injured pregnant woman should be transferred to a maternity facility when the injury is not life or limb threatening. In case of major trauma, stabilization and care of the woman is priority. Summary Several guidelines with high relevance for the care of pregnant women undergoing nonobstetric surgery have been published. Although the level of evidence may be low they can probably contribute to an improvement in the care and outcome of this patient group. © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Hohl M.K.,Kantonsspital Baden | Hauser N.,Kantonsspital Baden
Gynecological Surgery | Year: 2010

This study directly compares total intrafascial laparoscopic (TAIL™) hysterectomy with vaginal (VH) and abdominal (AH) hysterectomy with regard to safety, operating time and time of convalescence. The study is a prospective cohort study (Canadian Task Force classification II-2), including data from patients of a single university-affiliated teaching institution, admitted between 1997 and 2008 for hysterectomy due to benign uterus pathology. Patient data were collected pre-, intra- and postoperatively and complications documented using a standardised data sheet of a Swiss obstetric and gynaecological study group (Arbeitsgemeinschaft Schweizerische Frauenkliniken, Amlikon/Switzerland). Classification of complications (major complications and minor complications) for all three operation techniques, evaluation of surgeons and comparison of operation times and days of hospitalisation were analysed. 3066 patients were included in this study. 993 patients underwent AH, 642 VH and 1,431 total intrafascial hysterectomy. No statistically significant difference for the operation times comparing the three groups can be demonstrated. The mean hospital stay in the TAIL™ hysterectomy, VH and AH groups is 5.8± 2.4, 8.8±4.0 and 10.4±3.9 days, respectively. The postoperative minor complications including infection rates are low in the TAIL™ hysterectomy group (3.8%) when compared with either the AH group (15.3%) or the VH group (11.2%), respectively. The total of minor complications is statistically significant lower for TAIL™ hysterectomy as for AH (O.R. 4.52, CI 3.25-6.31) or VH (O.R. 3.16, CI 2.16-4.62). Major haemorrhage with consecutive reoperation is observed statistically significantly more frequent in the AH group when compared to the TAIL™ hysterectomy group, with an O.R. of 6.13 (CI 3.05-12.62). Overall, major intra- and postoperative complications occur significant more frequently in the AH group (8.6%) when compared to the VH group (3%) and the TAIL™ hysterectomy group (1.8%). The incidence of major complications applying the standardised TAIL™ hysterectomy technique is not related to the experience of the surgeons. We conclude that a standardised intrafascial technique of total laparoscopic (TAIL™) hysterectomy using an anatomically developed special uterine device is associated with a very low incidence of minor and major intra- and postoperative complications. The direct comparison of complication rates with either vaginal or abdominal hysterectomy favours the total laparoscopic technique, and therefore, this technique can be recommended as a relatively atraumatic procedure. The operation times are comparable for all three techniques without any statistically significant differences. This technique for laparoscopic hysterectomy is shown to be equally safe when applied by experienced gynaecologic surgeons or by residents in training. © The Author(s) 2010.

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