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Klaff R.,Linkoping University | Berglund A.,Eksatravagen 72 | Varenhorst E.,Linkoping University | Hedlund P.O.,Karolinska Institutet | And 2 more authors.
BJU International | Year: 2016

Objective To describe characteristics and quality-of-life (QoL), and to define factors associated with long-term survival in a subgroup of patients with prostate cancer with M1b disease. Patients and Methods The study was based on 915 patients from a prospective randomised multicentre trial (No. 5) by the Scandinavian Prostate Cancer Group, comparing parenteral oestrogen with total androgen blockade. Long-term survival was defined as patients having an overall survival of ≥10 years, and logistic regression models were constructed to identity clinical predictors of survival. QoL during follow-up was assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire - C30 version 1 (EORTC-C30) ratings. Results In all, 40 (4.4%) of the 915 men survived for >10 years. Factors significantly associated with increased likelihood of surviving for >10 years in the univariate analyses were: absence of cancer-related pain; Eastern Cooperative Oncology Group (ECOG) performance status of <2; negligible analgesic consumption; T-category of 1-2; prostate-specific antigen (PSA) level of <231 μg/L; and a Soloway score of 1. In the multivariate analyses, ECOG performance status of <2, PSA level of <231 μg/L, and Soloway score of 1, were all independent predictors of long-term survival. All subscales of the EORTC-C30 were higher in this group than for patients with short survival, but slowly declined over the decade. Conclusion A subgroup of patients with prostate cancer with M1b disease and certain characteristics showed a positive long-term response to androgen-deprivation therapy with an acceptable QoL over a decade or more. Independent predictors of long-term survival were identified as ECOG performance status of <2, limited extent of bone metastases (Soloway score of 1), and a PSA level of <231 μg/L at the time of enrolment. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd. Source


Arner P.,Karolinska University Hospital | Henjes F.,Affinity Technology | Schwenk J.M.,Affinity Technology | Darmanis S.,Affinity Technology | And 7 more authors.
PLoS ONE | Year: 2015

Background: Cancer cachexia (CC) is linked to poor prognosis. Although the mechanisms promoting this condition are not known, several circulating proteins have been proposed to contribute. We analyzed the plasma proteome in cancer subjects in order to identify factors associated with cachexia. Design/Subjects: Plasma was obtained from a screening cohort of 59 patients, newly diagnosed with suspected gastrointestinal cancer, with (n = 32) or without (n = 27) cachexia. Samples were subjected to proteomic profiling using 760 antibodies (targeting 698 individual proteins) from the Human Protein Atlas project. The main findings were validated in a cohort of 93 patients with verified and advanced pancreas cancer. Results: Only six proteins displayed differential plasma levels in the screening cohort. Among these, Carnosine Dipeptidase 1 (CNDP1) was confirmed by sandwich immunoassay to be lower in CC (p = 0.008). In both cohorts, low CNDP1 levels were associated with markers of poor prognosis including weight loss, malnutrition, lipid breakdown, low circulating albumin/IGF1 levels and poor quality of life. Eleven of the subjects in the discovery cohort were finally diagnosed with non-malignant disease but omitting these subjects from the analyses did not have any major influence on the results. Conclusions: In gastrointestinal cancer, reduced plasma levels of CNDP1 associate with signs of catabolism and poor outcome. These results, together with recently published data demonstrating lower circulating CNDP1 in subjects with glioblastoma and metastatic prostate cancer, suggest that CNDP1 may constitute a marker of aggressive cancer and CC. © 2015 Arner et al. Source


Flodin L.,Karolinska University Hospital | Flodin L.,Karolinska Institutet | Laurin A.,Karolinska Institutet | Lokk J.,Karolinska University Hospital | And 6 more authors.
Acta Orthopaedica | Year: 2016

Background and purpose - Hip fracture patients usually have low body mass index (BMI), and suffer further postoperative catabolism. How BMI relates to outcome in relatively healthy hip fracture patients is not well investigated. We investigated the association between BMI, survival, and independent living 1 year postoperatively.Patients and methods - This prospective multicenter study involved 843 patients with a hip fracture (mean age 82 (SD 7) years, 73% women), without severe cognitive impairment and living independently before admission. We investigated the relationship between BMI and both 1-year mortality and ability to return to independent living.Results - Patients with BMI > 26 had a lower mortality rate than those with BMI < 22 and those with BMI 22-26 (6%, 16%, and 18% respectively; p = 0.006). The odds ratio (OR) for 1-year survival in the group with BMI > 26 was 2.6 (95% CI: 1.2-5.5) after adjustment for age, sex, and physical status. Patients with BMI > 26 were also more likely to return to independent living after the hip fracture (OR = 2.6, 95% CI: 1.4-5.0). Patients with BMI < 22 had similar mortality and a similar likelihood of independent living to those with BMI 22-26.Interpretation - In this selected group of patients with hip fracture, the overweight and obese patients (BMI > 26) had a higher survival rate at 1 year, and returned to independent living to a higher degree than those of normal (healthy) weight. The obesity paradox and the recommendations for optimal BMI need further consideration in patients with hip fracture. © 2016 The Author(s). Published by Taylor & Francis on behalf of the Nordic Orthopedic Federation. Source


Sjoqvist S.,Advanced Center for Translational Regenerative Medicine | Jungebluth P.,Karolinska University Hospital | Ling Lim M.,Karolinska Institutet | Haag J.C.,University of Rome Tor Vergata | And 20 more authors.
Nature Communications | Year: 2014

A tissue-engineered oesophageal scaffold could be very useful for the treatment of pediatric and adult patients with benign or malignant diseases such as carcinomas, trauma or congenital malformations. Here we decellularize rat oesophagi inside a perfusion bioreactor to create biocompatible biological rat scaffolds that mimic native architecture, resist mechanical stress and induce angiogenesis. Seeded allogeneic mesenchymal stromal cells spontaneously differentiate (proven by gene-, protein and functional evaluations) into epithelial-And muscle-like cells. The reseeded scaffolds are used to orthotopically replace the entire cervical oesophagus in immunocompetent rats. All animals survive the 14-day study period, with patent and functional grafts, and gain significantly more weight than sham-operated animals. Explanted grafts show regeneration of all the major cell and tissue components of the oesophagus including functional epithelium, muscle fibres, nerves and vasculature. We consider the presented tissue-engineered oesophageal scaffolds a significant step towards the clinical application of bioengineered oesophagi. © 2014 Macmillan Publishers Limited. All rights reserved. Source


Fischler B.,Intervention and Technology CLINTEC | Nemeth A.,Intervention and Technology CLINTEC | Strom S.C.,Karolinska University Hospital
Journal of Internal Medicine | Year: 2012

Inherited metabolic diseases of the liver are characterized by deficiency of a hepatic enzyme or protein often resulting in life-threatening disease. The remaining liver function is usually normal. For most patients, treatment consists of supportive therapy, and the only curative option is liver transplantation. Hepatocyte transplantation is a promising therapy for patients with inherited metabolic liver diseases, which offers a less invasive and fully reversible approach. Procedure-related complications are rare. Here, we review the experience of hepatocyte transplantation for metabolic liver diseases and discuss the major obstacles that need to be overcome to establish hepatocyte transplantation as a reliable treatment option in the clinic. © 2012 The Association for the Publication of the Journal of Internal Medicine. Source

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