Eskilstuna, Sweden
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Paulsson G.,Central Hospital | Andersson S.,Malarsjukhuset | Sorbe B.,Örebro University
Anticancer Research | Year: 2013

Aim: The aim of the present study was to evaluate a consecutive series of ovarian carcinosarcomas with regard to prognosis, treatment and prognostic factors. Patients and Methods: A consecutive series of 81 ovarian carcinosarcomas from two well-defined geographic regions were studied with regard to survival, type of primary and adjuvant therapy and prognostic factors. All patients but one underwent primary surgery and some patients also received adjuvant chemotherapy (platinum-based) alone or in combination with radiotherapy. Univariate and multivariate Cox proportional regression analysis was used. Survival was analyzed by the Kaplan-Meier technique and differences were assessed by the log-rank test. Results: The mean age of the patients was 73 years. Fifty-one patients received adjuvant chemotherapy and nine patients pelvic irradiation. The 5-year overall survival rate was 10%. Adjuvant therapy (any type) and six completed cycles of chemotherapy were highly significant factors with regard to improved overall survival rate. The only significant tumor-associated prognostic factor was the International Federation of Gynecology and Obstetrics (FIGO) grade of the tumor. FIGO stage, site of metastatic spread, tumor size, histology, DNA ploidy, and tumor necrosis were nonsignificant factors. Therapy was rather well-tolerated and 29 patients (57%) completed at least six cycles of adjuvant chemotherapy. Conclusion: Adjuvant and completed chemotherapy according to the treatment plan were the most important prognostic factors. FIGO grade (grade 3 vs. 1-2) of the epithelial component of the tumor was also a significant prognostic factor in multivariate Cox analysis.


Lagerqvist B.,Uppsala University | Frobert O.,Örebro University | Olivecrona G.K.,Skåne University Hospital | Gudnason T.,Reykjavik University | And 19 more authors.
New England Journal of Medicine | Year: 2014

Methods We randomly assigned 7244 patients with STEMI to undergo manual thrombus aspiration followed by PCI or to undergo PCI alone, in a registry-based, randomized clinical trial. The primary end point of all-cause mortality at 30 days has been reported previously. Death from any cause at 1 year was a prespecified secondary end point of the trial.Results No patients were lost to follow-up. Death from any cause occurred in 5.3% of the patients (191 of 3621 patients) in the thrombus-aspiration group, as compared with 5.6% (202 of 3623) in the PCI-only group (hazard ratio, 0.94; 95% confidence interval [CI], 0.78 to 1.15; P = 0.57). Rehospitalization for myocardial infarction at 1 year occurred in 2.7% and 2.7% of the patients, respectively (hazard ratio, 0.97; 95% CI, 0.73 to 1.28; P = 0.81), and stent thrombosis in 0.7% and 0.9%, respectively (hazard ratio, 0.84; 95% CI, 0.50 to 1.40; P = 0.51). The composite of death from any cause, rehospitalization for myocardial infarction, or stent thrombosis occurred in 8.0% and 8.5% of the patients, respectively (hazard ratio, 0.94; 95% CI, 0.80 to 1.11; P = 0.48). The results were consistent across all the major subgroups, including grade of thrombus burden and coronary flow before PCI.Conclusions Routine thrombus aspiration before PCI in patients with STEMI did not reduce the rate of death from any cause or the composite of death from any cause, rehospitalization for myocardial infarction, or stent thrombosis at 1 year.BACKGROUND Routine intracoronary thrombus aspiration before primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) has not been proved to reduce short-term mortality. We evaluated clinical outcomes at 1 year after thrombus aspiration. Copyright © 2014 Massachusetts Medical Society.


Gojon H.,Karolinska Solna | Fawunmi D.,Malarsjukhuset | Valachis A.,Malarsjukhuset | Valachis A.,Uppsala University
European Journal of Surgical Oncology | Year: 2014

Background The aim of this meta-analysis is to evaluate the role of sentinel lymph node biopsy (SLNB) in patients with microinvasive breast cancer. Methods We searched MEDLINE and ISI Web of Science to identify studies including patients with microinvasive breast cancer who underwent SLNB and reported the rate of sentinel-node positivity. We performed proportion meta-analysis using either fixed or random-effects model based on the between-study heterogeneity. Findings A total of 24 studies including 968 patients met the eligibility criteria. The summary estimate for the sentinel-node (SN) positivity rate was 3.2% (95% Confidence Interval (CI): 2.1%-4.6%), 4.0% (95% CI 2.7%-5.5%), and 2.9% (95% CI: 1.6%-4.6%) for macrometastasis, micrometastasis and isolated tumor cells (ITC) respectively. Significant between-study heterogeneity was observed only in the meta-analysis of ITC positivity rate. Interpretation The amount of positive sentinel node in patients with proven microinvasive breast cancer is relatively low. As a result, the indications for SLNB in these patients should be probably individualized. © 2013 Elsevier Ltd. All rights reserved.


Valachis A.,Uppsala University | Nearchou A.,Malarsjukhuset | Lind P.,Malarsjukhuset | Lind P.,Karolinska Institutet | Mauri D.,PACMeR Panhellenic Association for Continual Medical Research
Breast Cancer Research and Treatment | Year: 2012

We compared the efficacy and safety of the addition of lapatinib versus trastuzumab or their combination to neoadjuvant chemotherapy in HER2-positive breast cancer. Potentially eligible trials were located through PubMed and Cochrane Library searches and abstracts of major international conferences. The endpoints that we assessed were pathologic complete response (pCR) rate, and toxicity. Pooled risk ratios (RR) were estimated for each endpoint with fixed or random effects models, depending on between studies heterogeneity. Six trials were identified with 1,494 eligible patients. The probability to achieve pCR was higher for the trastuzumab plus chemotherapy arm versus lapatinib plus chemotherapy (RR 1.25, 95 % confidence interval [CI] 1.08-1.43; p = 0.003) (6 trials; 1,494 patients). Probability to pCR was significantly higher in the group receiving lapatinib and trastuzumab than in the group with trastuzumab alone (RR 1.39, 95 %CI 1.20-1.63; p<0.001) (4 trials; 779 patients). Grade III-IV diarrhea and dermatologic toxicities were statistically more frequent in patients receiving lapatinib. No differences were observed regarding cardiac adverse events among patients receiving trastuzumab, lapatinib, or their combination. These data supports the superiority of a dual-HER2 inhibition for the treatment of HER2-positive breast cancer in the neoadjuvant setting. The direct comparison of trastuzumab and lapatinib showed that lapatinib is inferior in terms of pCR and associated with a higher risk for toxicity. © Springer Science+Business Media, LLC. 2012.


Briasoulis A.,University of Chicago | Agarwal V.,Roosevelt University | Valachis A.,Malarsjukhuset | Messerli F.H.,Roosevelt University
Journal of Clinical Hypertension | Year: 2013

In experimental studies, statins have been shown to lower blood pressure through increased nitric oxide bioavailability and improved arterial compliance. The clinical significance of this effect remains poorly documented. The authors performed a meta-analysis of the effect of statins on systolic blood pressure (SBP) and diastolic blood pressure (DBP) including prospective randomized, controlled trials of statin therapy. EMBASE and MEDLINE searches for studies in which patients were randomized to treatment with a statin plus standard treatment (or placebo) vs standard treatment (or placebo) were conducted. Studies that provided data on SBP and DBP values before the initiation of the treatment and at the end of the follow-up period were included. A total of 40 studies with 51 comparison groups examining 22,511 controls and 22,602 patients taking statins were examined. Mean SBP in the statin group decreased by 2.62 mm Hg (95% confidence interval [CI], -3.41 to -1.84; P<.001) and DBP by 0.94 mm Hg (95% CI, -1.31 to -0.57; P<.001). In studies including hypertensive patients, the decrease in blood pressures with statins was slightly greater (SBP, -3.07 mm Hg; 95% CI, -4.00 to -2.15 and DBP, 1.04; 95% CI, -1.47 to -0.61). Similarly, statins effectively reduced SBP in diabetic patients. In this large meta-analysis of prospective controlled studies, the authors found a small but statistically significant reduction of SBP in patients taking statins. The decrease in blood pressure may contribute to the pleiotropic effect of statins in reducing cardiovascular risk. © 2013 Wiley Periodicals, Inc.


Valachis A.,Malarsjukhuset | Valachis A.,Uppsala University | Nearchou A.D.,Malarsjukhuset | Lind P.,Malarsjukhuset | Lind P.,Karolinska Institutet
Breast Cancer Research and Treatment | Year: 2014

This meta-analysis investigates the oncological safety of breast-conserving therapy BCT in BRCA-mutation carriers and the risk for contralateral breast cancer (CBC) compared with non-carriers, potential risk factors for ipsilateral breast recurrence (IBR) or CBC and grades these factors based on the level of evidence. A PubMed search was conducted through April 2013 to identify studies that described the risk for IBR and CBC after BCT in BRCA-mutation carriers versus non-carriers as well as studies that investigated risk factors for IBR and CBC in BRCA-mutation carriers. Results were summarized using meta-analysis when sufficient studies were available. Ten studies investigated the oncological safety of BCT in BRCA-mutation carriers versus non-carriers. There was no significant difference in IBR between carriers and controls (RR 1.45, 95% CI 0.98-2.14). However, a significant higher risk for IBR in BRCA-mutation carriers was observed in studies with a median follow-up ≥7 years (RR 1.51, 95% CI 1.15-1.98). CBCs were significantly greater in carriers versus controls (RR 3.56, 95% CI 2.50-5.08). Use of adjuvant chemotherapy and oophorectomy were associated with a significantly lower risk for IBR in BRCA-mutation carriers. Three factors were associated with a lower risk for CBC in BRCA-mutation carriers: oophorectomy, use of tamoxifen, and age at first breast cancer. Based on current evidence, the use of BCT in BRCA-mutation carriers can be considered a reasonable option since it does not seem to increase the risk for IBR. However, several aspects should be taken into account before the final decision-making. © Springer Science+Business Media 2014.


Valachis A.,Malarsjukhuset | Valachis A.,Uppsala University | Nearchou A.,Malarsjukhuset
Acta Oncologica | Year: 2013

Background. The purpose of the meta-analysis was to estimate the effectiveness and toxicity of low activity radioiodine ablation versus high activity in patients with differentiated thyroid cancer (DTC). Design. A systematic review and meta-analysis was performed by including all randomized trials of low activity versus high activity radioiodine ablation after thyroidectomy. Standard meta-analytic procedures were used to analyze the study outcomes. Results. Ten trials were considered eligible and were further analyzed. The pooled risk ratio (RR) of having a successful ablation for an activity of 1100 MBq versus 3700 MBq (seven trials, 1772 patients) was 0.94 (95% CI 0.85-1.04, p-value = 0.21). The RR for successful ablation when only thyroid hormone withdrawal was used (five trials, 1116 patients) was 0.87 (95% CI 0.72-1.06, p-value = 0.17) and it was comparable to RR when only recombinant-human TSH (rec-hTSH) (two trials, 812 patients) was used (1.00, 95% CI 0.93-1.07, p-value = 0.92). Salivary dysfunction, nausea, and neck pain were significantly more frequent among patients with higher dose for ablation. Conclusion. Our meta-analysis provides some evidence from randomized trials that a lower activity of radioiodine ablation is as effective as higher dose after surgery in patients with DTC with lower toxicity. © 2013 Informa Healthcare.


Zavos A.,Senologic Hellenic Society | Valachis A.,Malarsjukhuset | Valachis A.,Uppsala University
Acta Oncologica | Year: 2016

Background: The aim of the study was to calculate the rate of chemotherapy-induced amenorrhea (CIA) after treatment with different adjuvant therapies in patients with breast cancer and to evaluate the risk factors for CIA based on the quality of evidence. Patient and methods: A search of PubMed and ISI Web of Science was performed. All published trials with female breast cancer patients who received adjuvant chemotherapy and presented data on the rate of CIA were considered eligible. The pooled rates of CIA were calculated by random effects model. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each potential risk factor for CIA by using the generic inverse weighted method. Results: We identified 580 potentially relevant studies, of which 75 were included in the analysis. Among 75 eligible studies, 19 different definitions of CIA have been used. The pooled rate of CIA was 55% (95% CI 50–60%) including 23 673 patients from 74 studies. The rate of CIA was increased by age with an estimate of 26% (95% CI 12–43%), 39% (95% CI 31–58%), and 77% (95% CI 71–83%) for women <35, 35–40, and >40 years old, respectively. Two risk factors were associated with the occurrence of CIA and were supported by strong level of evidence: older age (>40 years old), and the use of tamoxifen. Conclusions: This meta-analysis summarized the updated evidence on the impact of different adjuvant treatment regimens for breast cancer in menstruation and could serve as a helpful guide for oncologists during the discussion with their patients on fertility issues before decision on adjuvant therapy is made. A uniform definition of CIA is essential in future studies to make the interpretation of results more reliable. © 2016 Informa UK Limited, trading as Taylor & Francis Group.


Kofteridis D.P.,University of Crete | Valachis A.,Malarsjukhuset
Virus Adaptation and Treatment | Year: 2012

Epstein-Barr virus is a member of the human herpes virus family. Primary infection is usually asymptomatic in childhood; in adolescents and young adults, however, it leads to infectious mononucleosis with symptoms including fever, fatigue, and sore throat that can persist for months. The disease is usually self-limited and resolves over a period of weeks or months but may occasionally be complicated by a wide variety of complications. Symptomatic treatment, the cornerstone of therapy, includes adequate hydration, analgesics, antipyretics, and limitations of contact sports and activities. The role of antiviral treatment and corticosteroids is debatable and not recommended in general, while the development of vaccination is under investigation. This review concentrates on the diagnosis, the potential complications, and the therapeutic strategies in patients with infectious mononucleosis. © 2012 Valachis and Kofteridis, publisher and licensee Dove Medical Press Ltd.


Background: Oxaliplatin-induced peripheral neuropathy (OIPN) of acute and chronic type is well known, but long-term chronic type OIPN and its impact on quality of life (QoL) has not been extensively studied. Clinical experience indicates that oxaliplatin tolerance might vary with climate. Material and methods: Patient-reported chronic type OIPN and QoL among patients treated with oxaliplatin added to a fluoropyrimidine (Folfox or Capox) in the adjuvant setting of colorectal cancer (CRC) were assessed in a single center cross-sectional study by using the EORTC QLQ-CIPN20 and QLQ-C30 questionnaires. Comparison was made to patients treated with a fluoropyrimidine (5-FU or capecitabine) alone during the same time period. Results: Of 161 patients being disease-free 1–8 years after stop of treatment and invited, 84% participated; 65 treated with oxaliplatin and 71 with a fluoropyrimidine alone. Mean cumulative oxaliplatin dose was 567 mg/m2 (55% of planned dose). Oxaliplatin-treated patients reported statistically and clinically significant worse sensory as well as motor scale scores, dominated by symptoms from the feet. Severe tingling and numbness in toes/feet was reported by 38% and 37%, respectively, by oxaliplatin-treated patients compared with 8% for both by fluoropyrimidine alone patients (p < 0.001). Subgroup analyses indicated no impact of gender, age, regimen, time since stop of treatment or cumulated oxaliplatin dose for severity of the chronic type OIPN. The oxaliplatin compared with the fluoropyrimidine group reported worse QoL scores throughout all domains, with statistically and clinically significant differences for role and social function, nausea/loss of appetite and financial problems. Conclusions: Oxaliplatin added to a fluoropyrimidine for adjuvant treatment of CRC in a country with subarctic climate is associated with long-term, seemingly chronic, sensory neuropathy and impairment of QoL. This should be taken into account in clinical decision making on oxaliplatin treatment in the adjuvant setting. © 2016 Acta Oncologica Foundation

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