Sankt Gallen, Switzerland
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Untch M.,Helios Klinikum | Loibl S.,German Breast Group | Bischoff J.,Universitats Frauenklinik | Eidtmann H.,Universitats Frauenklinik | And 15 more authors.
The Lancet Oncology | Year: 2012

Background: We compared the efficacy and safety of the addition of lapatinib versus trastuzumab to anthracycline-taxane-based neoadjuvant chemotherapy. Methods: In the GeparQuinto randomised phase 3 trial, patients with untreated HER2-positive operable or locally advanced breast cancer were enrolled between Nov 7, 2007, and July 9, 2010. Patients were eligible if their tumours were classified as cT3/4a-d, or hormone receptor (HR)-negative, HR-positive with clinically node-positive and cT2 disease (cT2 cN+), or HR-positive and pathologically node-positive in the sentinel lymph node for those with cT1 disease (cT1 pN SLN+). Patients were randomly assigned in a 1:1 ratio to receive neoadjuvant treatment with four cycles of EC (epirubicin [90 mg/m 2 intravenously] plus cyclophosphamide [600 mg/m 2 intravenously], every 3 weeks), and four cycles of docetaxel (100 mg/m 2 intravenously every 3 weeks) with either trastuzumab (6 mg/kg intravenously, with a starting loading dose of 8 mg/kg, for eight cycles, every 3 weeks) or lapatinib (1000-1250 mg per day orally) throughout all cycles before surgery. Randomisation was done by dynamic allocation with the minimisation method of Pocock and patients were stratified by participating site, HR status, and extent of disease (cT1-3 cN0-2 vs T4 or N3). The primary endpoint was pathological complete response (defined as ypT0 and ypN0) and was analysed in all patients who received at least one cycle of EC. Participants and investigators were not masked to treatment assignment. Pathologists in centres assessing surgery outcomes were masked to group assignment. This trial is registered with ClinicalTrials.gov, number NCT00567554. Findings: Of 620 eligible patients, 309 were randomly assigned to chemotherapy with trastuzumab (ECH-TH group) and 311 to chemotherapy with lapatinib (ECL-TL group). Two patients in the ECH-TH group and three patients in the ECL-TL group did not start treatment because of withdrawal of consent or immediate surgery. 93 (30·3%) of 307 patients in the ECH-TH group and 70 (22·7%) of 308 patients in the ECL-TL group had a pathological complete response (odds ratio [OR] 0·68 [95%CI 0·47-0·97]; p=0·04). Chemotherapy with trastuzumab was associated with more oedema (119 [39·1%] vs 88 [28·7%]) and dyspnoea (90 [29·6%] vs 66 [21·4%]), and ECL-TL with more diarrhoea (231 [75·0%] vs 144 [47·4%]) and skin rash (169 [54·9%] vs 97 [31·9%]). 43 (14·0%) patients discontinued in the ECH-TH group and 102 (33·1%) in the ECL-TL group. 70 serious adverse events were reported in the ECH-TH group and 87 in the ECL-TL group. Interpretation: This direct comparison of trastuzumab and lapatinib showed that pathological complete response rate with chemotherapy and lapatinib was significantly lower than that with chemotherapy and trastuzumab. Unless long-term outcome data show different results, lapatinib should not be used outside of clinical trials as single anti-HER2-treatment in combination with neoadjuvant chemotherapy. Funding: GlaxoSmithKline, Roche, and Sanofi-Aventis. © 2012 Elsevier Ltd.


Aapro M.,Clinique de Genolier | Arends J.,Albert Ludwigs University of Freiburg | Bozzetti F.,University of Milan | Fearon K.,Royal Infirmary | And 7 more authors.
Annals of Oncology | Year: 2014

Background: Weight loss and cachexia are common, reduce tolerance of cancer treatment and the likelihood of response, and independently predict poor outcome. Methods: A group of experts met under the auspices of the European School of Oncology to review the literature and- on the basis of the limited evidence at present-make recommendations for malnutrition and cachexia management and future research. Conclusions: Our focus should move from end-stage wasting to supporting patients' nutritional and functional state throughout the increasingly complex and prolonged course of anti-cancer treatment. When inadequate nutrient intake predominates (malnutrition), this can be managed by conventional nutritional support. In the presence of systemic inflammation/ altered metabolism (cachexia), a multi-modal approach including novel therapeutic agents is required. For all patients, oncologists should consider three supportive care issues: ensuring sufficient energy and protein intake, maintaining physical activity to maintain muscle mass and (if present) reducing systemic inflammation. The results of phase II/III trials based on novel drug targets (e.g. cytokines, ghrelin receptor, androgen receptor, myostatin) are expected in the next 2 years. If effective therapies emerge, early detection of malnutrition and cachexia will be increasingly important in the hope that timely intervention can improve both patient-centered and oncology outcomes. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Muller F.,University of Basel | Christ-Crain M.,University of Basel | Bregenzer T.,Kantonsspital | Krause M.,Kantonsspital Munsterlingen | And 3 more authors.
Chest | Year: 2010

Background: Guidelines recommend blood culture sampling from hospitalized patients with suspected community-acquired pneumonia (CAP). However, the yield of true-positive results is low. We investigated the benefit of procalcitonin (PCT) on hospital admission to predict blood culture positivity in CAP. Methods: This was a prospective cohort study with a derivation and validation set including 925 patients with CAP who underwent blood culture sampling on hospital admission. Results: A total of 73 (7.9%) patients had true bacteremia (43 of 463 in the derivation cohort, 30 of 462 in the validation cohort). The area under the receiver operating characteristics curve of PCT in the derivation and validation cohorts was similar (derivation cohort, 0.83; 95% CI, 0.78-0.89; validation cohort, 0.79; 95% CI, 0.72-0.88). Overall, PCT was a significantly better predictor for blood culture positivity than WBC count, C-reactive protein, and other clinical parameters. In multivariate regression analysis, only antibiotic pretreatment (adjusted odds ratio, 0.25; P<.05) and PCT serum levels (adjusted odds ratio, 3.72; P<.001) were independent predictors. Overall, a PCT cutoff of 0.1 μg/L would enable reduction of the total number of blood cultures by 12.6% and still identify 99% of the positive blood cultures. Similarly, 0.25 μg/L and 0.5 μg/L cutoffs would enable reduction of blood cultures by 37% and 52%, respectively, and still identify 96% and 88%, respectively, of positive blood cultures. Conclusions: Initial PCT level accurately predicted blood culture positivity in patients with CAP. PCT measurement has the potential to reduce the number of drawn blood cultures in the emergency department and to implement a more targeted allocation of limited health-care resources. © 2010 American College of Chest Physicians.


Colditz M.J.,Royal Brisbane and Womens Hospital | Leyen K.V.,Kantonsspital | Jeffree R.L.,Royal Brisbane and Womens Hospital
Journal of Clinical Neuroscience | Year: 2012

The importance of the extent of resection for gliomas, and the utility of aminolevulinic acid (ALA) and protoporphyrin IX fluorescence in increasing the extent of resection, has become increasingly evident over the past decade. This review continues from Part 1 and focuses on the biochemical mechanisms by which ALA ingestion leads to tumour fluorescence, and discusses practicalities of the equipment and techniques needed to introduce ALA and fluorescence guided resection into neurosurgical practice. © 2012 Elsevier Ltd. All rights reserved.


Mojon-Azzi S.M.,University of St. Gallen | Kunz A.,Kantonsspital | Mojon D.S.,Kantonsspital | Mojon D.S.,University of Bern
British Journal of Ophthalmology | Year: 2011

Aim: To determine the social acceptance of children with strabismus by their peers and to determine the age at which the negative impact of strabismus on psychosocial interactions emerges. Methods: Photographs of six children were digitally altered in order to create pictures of identical twins except for the position of the eyes (orthotropic, exotropic and exotropic) and the colour of the shirt. One hundred and eighteen children aged 3-12 years were asked to select, for each of the six twin pairs, one of the twins to invite to their birthday party. The grouping of the pictures and the composition of the twin pairs were determined by Latin squares. Results: Children younger than 6 years old did not make any significant distinctions between orthotropic children and children with strabismus. Respondents aged 6 years or older invited children with a squint to their birthday parties significantly less often than orthotropic children. The authors found no impact (p>0.1) of gender, of the colour of the shirt or of the type of strabismus, but did find a highly significant impact of age on the number of invited children with strabismus. Conclusions: Children aged 6 years or older with a visible squint seem to be less likely to be accepted by their peers. Because this negative attitude towards strabismus appears to emerge at approximately the age of 6 years, corrective surgery for strabismus without prospects for binocular vision should be performed before this age.


Brack T.,Kantonsspital | Randerath W.,Witten/Herdecke University | Bloch K.E.,University of Zürich
Respiration | Year: 2012

Cheyne-Stokes respiration (CSR) is characterized by a pattern of cyclic oscillations of tidal volume and respiratory rate with periods of hyperpnea alternating with hypopnea or apnea in patients with heart failure. CSR harms the failing heart through intermittent hypoxia brought about by apnea and hypopnea and recurrent sympathetic surges. CSR impairs the quality of life and increases cardiac mortality in patients with heart failure. Thus, CSR should actively be pursued in patients with severe heart failure. When CSR persists despite optimal therapy of heart failure, noninvasive adaptive servoventilation is currently the most promising treatment. Copyright © 2011 S. Karger AG, Basel.


Gillessen S.,Kantonsspital | Templeton A.,Kantonsspital | Marra G.,University of Zürich | Kuo Y.-F.,University of Texas Medical Branch | And 2 more authors.
Journal of the National Cancer Institute | Year: 2010

BackgroundAndrogen deprivation with gonadotropin-releasing hormone (GnRH) agonists or orchiectomy is a common but controversial treatment for prostate cancer. Uncertainties remain about its use, particularly with increasing recognition of serious side effects. In animal studies, androgens protect against colonic carcinogenesis, suggesting that androgen deprivation may increase the risk of colorectal cancer.MethodsWe identified 107859 men in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database who were diagnosed with prostate cancer in 1993 through 2002, with follow-up available through 2004. The primary outcome was development of colorectal cancer, determined from SEER files on second primary cancers. Cox proportional hazards regression was used to assess the influence of androgen deprivation on the outcome, adjusted for patient and prostate cancer characteristics. All statistical tests were two-sided.ResultsMen who had orchiectomies had the highest unadjusted incidence rate of colorectal cancer (6.3 per 1000 person-years; 95% confidence interval [CI] = 5.3 to 7.5), followed by men who had GnRH agonist therapy (4.4 per 1000 person-years; 95% CI = 4.0 to 4.9), and men who had no androgen deprivation (3.7 per 1000 person-years; 95% CI = 3.5 to 3.9). After adjustment for patient and prostate cancer characteristics, there was a statistically significant dose-response effect (Ptrend =. 010) with an increasing risk of colorectal cancer associated with increasing duration of androgen deprivation. Compared with the absence of these treatments, there was an increased risk of colorectal cancer associated with use of GnRH agonist therapy for 25 months or longer (hazard ratio [HR] = 1.31, 95% CI = 1.12 to 1.53) or with orchiectomy (HR = 1.37, 95% CI = 1.14 to 1.66).ConclusionLong-term androgen deprivation therapy for prostate cancer is associated with an increased risk of colorectal cancer. © 2010 The Author.


Postinfectious glomerulonephritis is an immune-mediated disease occurring as a result of the host response to an extrarenal infection. The classical form of poststreptococcal disease is decreasing worldwide but remains a significant health care problem in developing countries, especially in children. In industrialised countries postinfectious glomerulonephritis is now primarily due to non-streptococcal disease. In elderly patients with risk factors such as diabetes mellitus, alcohol-dependency or neoplasia and in intravenous drug users postinfectious glomerulonephritis is most often associated with staphylococcal infections of various locations. Compared to the good outcome of classical poststreptococcal glomerulonephritis the severity of the nephritic syndrom is increased and the prognosis is worse, especially if pre-existing renal disease such as diabetic or vascular nephropathy is present. The recognition and adequate therapy, often including surgical measures, of the primary focus of infection is of utmost importance to improve the outcome of this condition. Especially in patients with diabetic foot syndrome and in intravenous drug users with signs of infection and renal insufficiency or abnormal urinalysis, there should be a high index of suspicion for postinfectious glomerulonephritis. © 2015 Verlag Hans Huber, Hogrefe AG, Bern.


Piso R.J.,Kantonsspital | Rothen M.,Regionalspital | Rothen J.P.,Medical Laboratories Olten | Stahl M.,Kantonsspital
Journal of Acquired Immune Deficiency Syndromes | Year: 2011

Objectives: Osteoporosis and bone fractures are correlated to antiretroviral treatment. It is not clear whether some substances comprise greater risks of bone loss than others. Methods: We measured pyridinoline, deoxypyridinoline crosslinks, and bone-specific alkaline phosphatase in 113 HIV-positive patients. We compared patients with and without antiretroviral treatment. We then compared patients with versus without tenofovir and patients with protease inhibitor versus nonnucleoside reverse transcriptase inhibitor use. Results: Bone-specific alkaline phosphatase, pyridinoline, and deoxypyridinoline crosslinks were significantly higher in patients with antiretroviral treatment compared with patients without antiretroviral treatment: 24.5 versus 13.04 pg/L (P < 0.001), 82.73 versus 51.93 nmol/mmol (P < 0.001), and 16.56 versus 9.94 nmol/mmol (P < 0.001), respectively. In contrast, no difference was found between patients with and without tenofovir: 25.38 versus 20.02 pg/l (P = 0.1); 79.85 versus 83.95 nmol/mmol (P = 0.64), and 19.12 versus 14.00 nmol/mmol (P = 0.14), respectively. Comparison between patients with protease inhibitor versus nonnucleoside reverse transcriptase inhibitor yielded no difference either: 23.07 versus 27.18 pg/L (P = 0.24), 92.96 versus 80.73 nmol/mmol (P = 0.36), and 18.22 versus 16.39 nmol/mmol (P = 0.55). CONCLUSION:: Markers for bone turnover are higher in treated compared with untreated patients. No difference concerning tenofovir use or protease inhibitor versus nonnucleoside reverse transcriptase inhibitor use could be found. © 2011 Lippincott Williams & Wilkins.


Thurnheer R.,Kantonsspital
Expert Review of Respiratory Medicine | Year: 2011

Respiratory disorders in sleep are highly prevalent and increasingly recognized. Among these, obstructive sleep apnea, resulting in daytime fatigue and somnolence, increased risk of workplace and traffic accidents but also psychosocial dysfunction, is most often diagnosed. As an independent risk factor for cardiovascular and metabolic disease, obstructive sleep apnea has recently attracted even more attention. Apart from continuous positive airway pressure, only a few alternative treatment options are available. Individual history is still most important for selecting patients for sleep studies. Fatigue and a high subjective propensity to fall asleep during the daytime, a history of snoring and breathing pauses during sleep combined with anthropometric risk factors make a diagnosis very likely. Other night-time respiratory disorders include central sleep apnea, Cheyne-Stokes respiration, obesity hypoventilation syndrome and mixed sleep apnea syndromes. The diagnosis of sleep-disordered breathing can be made by comprehensive sleep studies in a sleep laboratory, but also using portable equipment for cardiorespiratory monitoring and measurement of oxygen desaturation at home, according to pretest probabilities, individual experience and local preferences. © 2011 Expert Reviews Ltd.

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