uu.seUppsala universitets publikationer
Ändra sökning
Avgränsa sökresultatet
3456789 251 - 300 av 1999
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 251. Brédart, A.
    et al.
    Razavi, D.
    Robertson, C.
    Batel-Copel, L.
    Larsson, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Lichosik, D.
    Meyza, J.
    Schraub, S.
    von Essen, Louise
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    de Haes, J. C.
    A comprehensive assessment of satisfaction with care: preliminary psychometric analysis in French, Polish, Swedish and Italian oncology patients2001Ingår i: Patient Education and Counseling, ISSN 0738-3991, E-ISSN 1873-5134, Vol. 43, nr 3, s. 243-252Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Satisfaction with care may be closely related to quality of life in cancer patients. This evaluation is especially relevant when quality of care is considered. The present study assessed whether equivalent scaling properties could be found in a comprehensive assessment of satisfaction with care (CASC) administered in cancer patients from French, Polish and Swedish oncology settings, in comparison to the scaling properties previously evidenced in the CASC with an Italian sample. A total of 140, 186 and 133 oncology patients were approached in France, Poland and Sweden, respectively. Specific items in the CASC were identified as consistently omitted across country samples. Multitrait scaling analysis on an item-grouping adapted for the French, Polish, Swedish and Italian samples provided excellent internal consistencies and convergent validity estimates. Discriminant validity proved less satisfactory, evidencing overlap between hypothesised care dimensions across country samples. The identification of omitted or overlapping items will lead to the design of a revised CASC version to further test in larger cross-cultural samples.

  • 252. Bujko, K.
    et al.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Valentini, V.
    Michalski, W.
    Spalek, M.
    Postoperative chemotherapy in patients with rectal cancer receiving preoperative radio(chemo)therapy: A meta-analysis of randomized trials comparing surgery +/- a fluoropyrimidine and surgery plus a fluoropyrimidine +/- oxaliplatin2015Ingår i: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 41, nr 6, s. 713-723Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: There is no consensus on the role of postoperative chemotherapy in patients with rectal cancer who have received preoperative radio(chemo)therapy. Materials and methods: A systematic review and meta-analysis were performed of trials that used preoperative radio(chemo)therapy and randomized patients either between postoperative chemotherapy and observation or between a fluoropyrimidine only (FU-only) and a fluoropyrimidine with oxaliplatin (FU-OXA) as postoperative chemotherapy. Results: Five randomized studies compared postoperative chemotherapy with observation in a total of 2398 patients. None of these trials demonstrated a statistically significant benefit of chemotherapy for OS and DFS. The pooled differences in OS and DFS did not differ statistically significantly between the chemotherapy group and the observation group. The hazard ratios (HRs) and 95% confidence intervals (CIs) were 0.95 (CI: 0.82-1.10), P = 0.49 and 0.92 (CI: 0.80-1.04), P = 0.19, respectively. In the subgroup of trials in which randomization was performed after surgery (n = 753), a statistically significant positive pooled chemotherapy effect was observed for DFS (HR = 0.79, 95% CI: 0.62-1.00, P = 0.047), but not for OS (P = 0.39). Four randomized trials compared adjuvant FU OXA with adjuvant FU-only in 2710 patients. In two trials, the difference in DFS between groups was statistically significant in favour of FU OXA, and in the other two trials, the difference was not significant. The pooled difference in DFS between the FU OXA group and the FU-only group was not statistically significant: HR = 0.84 (CI: 0.66-1.06), P = 0.15. Conclusion: The use of postoperative chemotherapy in patients with rectal cancer receiving preoperative radio(chemo)therapy is not based on strong scientific evidence. (C) 2015 Elsevier Ltd. All rights reserved.

  • 253. Bujko, Krzysztof
    et al.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Adjuvant chemotherapy for rectal cancer2014Ingår i: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 15, nr 6, s. E194-E195Artikel i tidskrift (Refereegranskat)
  • 254.
    Busse, Niels
    et al.
    Univ Bremen, Islet Biol Lab, Bremen, Germany..
    Paroni, Federico
    Univ Bremen, Islet Biol Lab, Bremen, Germany..
    Richardson, Sarah J.
    Univ Exeter, Islet Biol Exeter, Med, Exeter EX4 4QJ, Devon, England..
    Laiho, Jutta E.
    Univ Tampere, Sch Med, Dept Virol, Tampere, Finland..
    Oikarinen, Maarit
    Univ Tampere, Sch Med, Dept Virol, Tampere, Finland..
    Frisk, Gun
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Hyoty, Heikki
    Univ Tampere, Sch Med, Dept Virol, Tampere, Finland.;Pirkanmaa Hosp Dist, Fimlab Labs, Tampere, Finland..
    de Koning, Eelco
    Leiden Univ, Med Ctr, Dept Internal Med, Leiden, Netherlands.;Univ Med Ctr Utrecht, Hubrecht Inst, Utrecht, Netherlands..
    Morgan, Noel G.
    Univ Exeter, Islet Biol Exeter, Med, Exeter EX4 4QJ, Devon, England..
    Maedler, Kathrin
    Univ Bremen, Islet Biol Lab, Bremen, Germany..
    Detection and localization of viral infection in the pancreas of patients with type 1 diabetes using short fluorescently-labelled oligonucleotide probes2017Ingår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, nr 8, s. 12620-12636Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Enteroviruses, specifically of the Coxsackie B virus family, have been implicated in triggering islet autoimmunity and type 1 diabetes, but their presence in pancreata of patients with diabetes has not been fully confirmed. To detect the presence of very low copies of the virus genome in tissue samples from T1D patients, we designed a panel of fluorescently labeled oligonucleotide probes, each of 17-22 nucleotides in length with a unique sequence to specifically bind to the enteroviral genome of the picornaviridae family. With these probes enteroviral RNA was detected with high sensitivity and specificity in infected cells and tissues, including in FFPE pancreas sections from patients with T1D. Detection was not impeded by variations in sample processing and storage thereby overcoming the potential limitations of fragmented RNA. Co-staining of small RNA probes in parallel with classical immunstaining enabled virus detection in a cell-specific manner and more sensitively than by viral protein.

  • 255. Butt, Salma
    et al.
    Butt, Talha
    Jirstrom, Karin
    Hartman, Linda
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Zhou, Wenjing
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Wärnberg, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Borgquist, Signe
    The Target for Statins, HMG-CoA Reductase, Is Expressed in Ductal Carcinoma-In Situ and May Predict Patient Response to Radiotherapy2014Ingår i: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 21, nr 9, s. 2911-2919Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Patients with ductal carcinoma-in-situ (DCIS) are currently not prescribed adjuvant systemic treatment after surgery and radiotherapy. Prediction of DCIS patients who would benefit from radiotherapy is warranted. Statins have been suggested to exert radio-sensitizing effects. The target for cholesterol-lowering statins is HMG-CoA reductase (HMGCR), the rate-limiting enzyme in the mevalonate pathway. The aim of this study was to examine HMGCR expression in DCIS and study its treatment predictive value. Methods. A population-based cohort including 458 women diagnosed with primary DCIS between 1986 and 2004 were followed until November 2011 to study long-term survival. Tumor tissue microarrays were constructed, and immunohistochemical analyses were performed to detect cytoplasmic protein expression of HMGCR. The association between DCIS HMGCR expression and invasive breast cancer recurrence-free survival (RFSinv) and overall survival (OS) was analyzed by Kaplan-Meier curves, log rank test, and Cox proportional hazard analysis. Results. HMGCR was strongly expressed in 24 % of the assessed DCIS samples, moderately expressed in 46 %, and weakly expressed in 23 %; no expression was detected in 7 % of the samples. During the follow-up time (median 13.8 years), 61 patients were diagnosed with an invasive breast cancer recurrence, and 80 patients died. A crude analysis showed no survival benefit from radiotherapy. However, patients with strong HMGCR expression showed an improved RFSinv (log rank, p = 0.03) and OS (log rank, p = 0.04) after radiotherapy. No statistically significant interaction was observed for HMGCR and radiotherapy (RFSinv p = 0.69 and OS p = 0.29). Conclusions. This study demonstrates HMGCR expression in DCIS and suggests HMGCR as a predictive marker of response to postoperative radiotherapy in DCIS, although the test for interaction was nonsignificant. Future DCIS studies addressing the potential of statin treatment targeting HMGCR are warranted.

  • 256.
    Bychkov, Dmitrii
    et al.
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland..
    Linder, Nina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Internationell mödra- och barnhälsovård (IMCH), Internationell barnhälsa och nutrition. Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland..
    Turkki, Riku
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland..
    Nordling, Stig
    Univ Helsinki, Dept Pathol, Med, Helsinki, Finland..
    Kovanen, Panu E.
    Univ Helsinki, Dept Pathol, Helsinki, Finland.;Helsinki Univ Hosp, HUSLAB, Helsinki, Finland..
    Verrill, Clare
    Univ Oxford, Nuffield Dept Surg Sci, NIHR Oxford Biomed Res Ctr, Oxford, England..
    Walliander, Margarita
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland..
    Lundin, Mikael
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland..
    Haglund, Caj
    Univ Helsinki, Dept Surg, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland.;Univ Helsinki, Res Programs Unit, Translat Canc Biol, Helsinki, Finland..
    Lundin, Johan
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland.;Karolinska Inst, Dept Publ Hlth Sci, Global Hlth IHCAR, Stockholm, Sweden..
    Deep learning based tissue analysis predicts outcome in colorectal cancer2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikel-id 3395Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Image-based machine learning and deep learning in particular has recently shown expert-level accuracy in medical image classification. In this study, we combine convolutional and recurrent architectures to train a deep network to predict colorectal cancer outcome based on images of tumour tissue samples. The novelty of our approach is that we directly predict patient outcome, without any intermediate tissue classification. We evaluate a set of digitized haematoxylin-eosin-stained tumour tissue microarray (TMA) samples from 420 colorectal cancer patients with clinicopathological and outcome data available. The results show that deep learning-based outcome prediction with only small tissue areas as input outperforms (hazard ratio 2.3; CI 95% 1.79-3.03; AUC 0.69) visual histological assessment performed by human experts on both TMA spot (HR 1.67; CI 95% 1.28-2.19; AUC 0.58) and whole-slide level (HR 1.65; CI 95% 1.30-2.15; AUC 0.57) in the stratification into low-and high-risk patients. Our results suggest that state-of-the-art deep learning techniques can extract more prognostic information from the tissue morphology of colorectal cancer than an experienced human observer.

  • 257.
    Bystry, Vojtech
    et al.
    Masaryk Univ, CEITEC Cent European Inst Technol, Brno, Czech Republic..
    Agathangelidis, Andreas
    IRCCS San Raffaele Sci Inst, Div Mol Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Bikos, Vasilis
    Masaryk Univ, CEITEC Cent European Inst Technol, Brno, Czech Republic..
    Sutton, Lesley Ann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Baliakas, Panagiotis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Hadzidimitriou, Anastasia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Stamatopoulos, Kostas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Darzentas, Nikos
    Masaryk Univ, CEITEC Cent European Inst Technol, Brno, Czech Republic..
    ARResT/AssignSubsets: a novel application for robust subclassification of chronic lymphocytic leukemia based on B cell receptor IG stereotypy2015Ingår i: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 31, nr 23, s. 3844-3846Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Motivation: An ever-increasing body of evidence supports the importance of B cell receptor immunoglobulin (BcR IG) sequence restriction, alias stereotypy, in chronic lymphocytic leukemia (CLL). This phenomenon accounts for similar to 30% of studied cases, one in eight of which belong to major subsets, and extends beyond restricted sequence patterns to shared biologic and clinical characteristics and, generally, outcome. Thus, the robust assignment of new cases to major CLL subsets is a critical, and yet unmet, requirement. Results: We introduce a novel application, ARResT/AssignSubsets, which enables the robust assignment of BcR IG sequences from CLL patients to major stereotyped subsets. ARResT/AssignSubsets uniquely combines expert immunogenetic sequence annotation from IMGT/V-QUEST with curation to safeguard quality, statistical modeling of sequence features from more than 7500 CLL patients, and results from multiple perspectives to allow for both objective and subjective assessment. We validated our approach on the learning set, and evaluated its real-world applicability on a new representative dataset comprising 459 sequences from a single institution.

  • 258. Byström, P
    et al.
    Frödin, J-E
    Berglund, A
    Wilking, Nils
    Glimelius, Bengt
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi. Enheten för onkologi.
    Phase I study of UFT plus leucovorin with radiotherapy in patients with inextirpable non-rectal gastrointestinal cancer.2004Ingår i: Radiother Oncol, ISSN 0167-8140, Vol. 70, nr 2, s. 171-5Artikel i tidskrift (Övrigt vetenskapligt)
  • 259. Byström, P.
    et al.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Reply to FDG-PET: for early prediction of response to the first-line chemotherapy in metastatic colorectal cancer?2009Ingår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 20, nr 6, s. 1150-1150Artikel i tidskrift (Refereegranskat)
  • 260.
    Byström, Per
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Berglund, Åke
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Wernroth, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Johansson, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Evaluation of predictive markers for patients with advanced colorectal cancer2012Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, nr 7, s. 849-859Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background.

    To evaluate the predictive and prognostic value of serum and plasma tumor markers, in comparison with clinical and biomedical parameters for response rate (RR), progression-free survival (PFS) and overall survival (OS) among patients with metastatic colorectal cancer (mCRC) treated with combination chemotherapy.

    Material and methods.

    One-hundred and six patients with mCRC from three centers, part of a multicenter study, received irinotecan with the Nordic bolus 5-fluorouracil (5-FU) and folinic acid schedule (FLIRI) or the de Gramont schedule (Lv5FU2-IRI). Blood samples for CEA, CA19-9, TPA, TIMP-1, SAA, transthyretin and CRP were taken at baseline and after two, four and eight weeks of treatment. Tumor marker levels at baseline and longitudinally were compared with responses evaluated (CT/MRI) after two and four months of treatment. The correlations to RR, PFS and OS were evaluated with regression analyses.

    Results.

    A significant correlation to OS was seen for baseline levels of all markers. In multivariate analyses with clinical parameters, TPA, CRP, SAA and TIMP-1 provided independent information. The baseline values of CEA, TPA and TIMP-1 were also significantly correlated to PFS and TPA to RR. Changes during treatment, i.e. the slope gave with the exception of CA19-9 for OS less information about outcomes. The best correlation to response was seen for CEA, CA19-9 and TPA with AUC values of 0.78, 0.83 and 0.79, respectively, using a combined model based upon an interaction between the slope and the baseline value.

    Conclusions.

    Baseline tumor markers together with clinical parameters provide prognostic information about survival in patients with mCRC. The ability of the individual tumor markers to predict treatment response and PFS is limited. Changes in marker levels during the first two months of treatment are less informative of outcome.

  • 261.
    Byström, Per
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Johansson, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Berglund, Åke
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Sorbye, H
    Tveit, KM
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Health-related quality of life in patients with metastatic colorectal cancer receiving palliative combination chemotherapy2012Artikel i tidskrift (Refereegranskat)
  • 262.
    Byström, Sanna
    et al.
    KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
    Fredolini, Claudia
    KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
    Edqvist, Per-Henrik D
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Nyaiesh, Etienne-Nicholas
    KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
    Drobin, Kimi
    KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
    Uhlen, Mathias
    KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
    Bergqvist, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Gavle Sjukhus, S-80188 Gavle, Sweden.;Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden..
    Ponten, Fredrik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Schwenk, Jochen M.
    KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
    Affinity Proteomics Exploration of Melanoma Identifies Proteins in Serum with Associations to T-Stage and Recurrence2017Ingår i: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 10, nr 3, s. 385-395Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Blood-based proteomic profiling may aid and expand our understanding of diseases and their different phenotypes. The aim of the presented study was to profile serum samples from patients with malignant melanoma using affinity proteomic assays to describe proteins in the blood stream that are associated to stage or recurrence of melanoma. MATERIAL AND METHODS: Multiplexed protein analysis was conducted using antibody suspension bead arrays. A total of 232 antibodies against 132 proteins were selected from (i) a screening with 4595 antibodies and 32 serum samples from melanoma patients and controls, (ii) antibodies used for immunohistochemistry, (iii) protein targets previously related with melanoma. The analysis was performed with 149 serum samples from patients with malignant melanoma. Antibody selectivity was then assessed by Western blot, immunocapture mass spectrometry, and epitope mapping. Lastly, indicative antibodies were applied for IHC analysis of melanoma tissues. RESULTS: Serum levels of regucalcin (RGN) and syntaxin 7 (STX7) were found to be lower in patients with both recurring tumors and a high Breslow's thickness (T-stage 3/4) compared to low thickness (T-stage 1/2) without disease recurrence. Serum levels of methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) were instead elevated in sera of T3/4 patients with recurrence. The analysis of tissue sections with S100A6 and MTHFD1L showed positive staining in a majority of patients with melanoma, and S100A6 was significantly associated to T-stage. CONCLUSIONS: Our findings provide a starting point to further study RGN, STX7, MTHFD1L and S100A6 in serum to elucidate their involvement in melanoma progression and to assess a possible contribution to support clinical indications.

  • 263.
    Bäcklin, Christofer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Machine Learning Based Analysis of DNA Methylation Patterns in Pediatric Acute Leukemia2015Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer in the Nordic countries. Recent evidence indicate that DNA methylation (DNAm) play a central role in the development and progression of the disease.

    DNAm profiles of a collection of ALL patient samples and a panel of non-leukemic reference samples were analyzed using the Infinium 450k methylation assay. State-of-the-art machine learning algorithms were used to search the large amounts of data produced for patterns predictive of future relapses, in vitro drug resistance, and cytogenetic subtypes, aiming at improving our understanding of the disease and ultimately improving treatment.

    In paper I, the predictive modeling framework developed to perform the analyses of DNAm dataset was presented. It focused on uncompromising statistical rigor and computational efficiency, while allowing a high level of modeling flexibility and usability. In paper II, the DNAm landscape of ALL was comprehensively characterized, discovering widespread aberrant methylation at diagnosis strongly influenced by cytogenetic subtype. The aberrantly methylated regions were enriched for genes repressed by polycomb group proteins, repressively marked histones in healthy cells, and genes associated with embryonic development. A consistent trend of hypermethylation at relapse was also discovered. In paper III, a tool for DNAm-based subtyping was presented, validated using blinded samples and used to re-classify samples with incomplete phenotypic information. Using RNA-sequencing, previously undetected non-canonical aberrations were found in many re-classified samples. In paper IV, the relationship between DNAm and in vitro drug resistance was investigated and predictive signatures were obtained for seven of the eight therapeutic drugs studied. Interpretation was challenging due to poor correlation between DNAm and gene expression, further complicated by the discovery that random subsets of the array can yield comparable classification accuracy. Paper V presents a novel Bayesian method for multivariate density estimation with variable bandwidths. Simulations showed comparable performance to the current state-of-the-art methods and an advantage on skewed distributions.

    In conclusion, the studies characterize the information contained in the aberrant DNAm patterns of ALL and assess its predictive capabilities for future relapses, in vitro drug sensitivity and subtyping. They also present three publicly available tools for the scientific community to use.

    Delarbeten
    1. Developer-Friendly and Computationally Efficient Predictive Modeling without Information Leakage: The emil Package for R
    Öppna denna publikation i ny flik eller fönster >>Developer-Friendly and Computationally Efficient Predictive Modeling without Information Leakage: The emil Package for R
    2018 (Engelska)Ingår i: Journal of Statistical Software, ISSN 1548-7660, E-ISSN 1548-7660, Vol. 85, nr 13, s. 1-30Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Data driven machine learning for predictive modeling problems (classification, regression, or survival analysis) typically involves a number of steps beginning with data preprocessing and ending with performance evaluation. A large number of packages providing tools for the individual steps are available for R, but there is a lack of tools for facilitating rigorous performance evaluation of the complete procedures assembled from them by means of cross-validation, bootstrap, or similar methods. Such a tool should strictly prevent test set observations from influencing model training and meta- parameter tuning, so- called information leakage, in order to not produce overly optimistic performance estimates. Here we present a new package for R denoted emil (evaluation of modeling without information leakage) that offers this form of performance evaluation. It provides a transparent and highly customizable framework for facilitating the assembly, execution, performance evaluation, and interpretation of complete procedures for classification, regression, and survival analysis. The components of package emil have been designed to be as modular and general as possible to allow users to combine, replace, and extend them if needed. Package emil was also developed with scalability in mind and has a small computational overhead, which is a key requirement for analyzing the very big data sets now available in fields like medicine, physics, and finance. First package emil's functionality and usage is explained. Then three specific application examples are presented to show its potential in terms of parallelization, customization for survival analysis, and development of ensemble models. Finally a brief comparison to similar software is provided.

    Ort, förlag, år, upplaga, sidor
    JOURNAL STATISTICAL SOFTWARE, 2018
    Nyckelord
    predictive modeling, machine learning, performance evaluation, resampling, high performance computing
    Nationell ämneskategori
    Datavetenskap (datalogi) Beräkningsmatematik
    Identifikatorer
    urn:nbn:se:uu:diva-362159 (URN)10.18637/jss.v085.i13 (DOI)000440230100001 ()
    Forskningsfinansiär
    Stiftelsen för strategisk forskning (SSF), RBc08-008Vetenskapsrådet, 621-2008-5854
    Tillgänglig från: 2018-10-19 Skapad: 2018-10-19 Senast uppdaterad: 2018-10-19Bibliografiskt granskad
    2. Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia
    Öppna denna publikation i ny flik eller fönster >>Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia
    Visa övriga...
    2013 (Engelska)Ingår i: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 14, nr 9, s. r105-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND:

    Although aberrant DNA methylation has been observed previously in acute lymphoblastic leukemia (ALL), the patterns of differential methylation have not been comprehensively determined in all subtypes of ALL on a genome-wide scale. The relationship between DNA methylation, cytogenetic background, drug resistance and relapse in ALL is poorly understood.

    RESULTS:

    We surveyed the DNA methylation levels of 435,941 CpG sites in samples from 764 children at diagnosis of ALL and from 27 children at relapse. This survey uncovered four characteristic methylation signatures. First, compared with control blood cells, the methylomes of ALL cells shared 9,406 predominantly hypermethylated CpG sites, independent of cytogenetic background. Second, each cytogenetic subtype of ALL displayed a unique set of hyper- and hypomethylated CpG sites. The CpG sites that constituted these two signatures differed in their functional genomic enrichment to regions with marks of active or repressed chromatin. Third, we identified subtype-specific differential methylation in promoter and enhancer regions that were strongly correlated with gene expression. Fourth, a set of 6,612 CpG sites was predominantly hypermethylated in ALL cells at relapse, compared with matched samples at diagnosis. Analysis of relapse-free survival identified CpG sites with subtype-specific differential methylation that divided the patients into different risk groups, depending on their methylation status.

    CONCLUSIONS:

    Our results suggest an important biological role for DNA methylation in the differences between ALL subtypes and in their clinical outcome after treatment.

    Nationell ämneskategori
    Medicinsk genetik
    Identifikatorer
    urn:nbn:se:uu:diva-208296 (URN)10.1186/gb-2013-14-9-r105 (DOI)000328195700011 ()24063430 (PubMedID)
    Anmärkning

    De två första författarna delar förstaförfattarskapet.

    Tillgänglig från: 2013-09-27 Skapad: 2013-09-27 Senast uppdaterad: 2019-10-23Bibliografiskt granskad
    3. DNA methylation-based subtype prediction for pediatric acute lymphoblastic leukemia
    Öppna denna publikation i ny flik eller fönster >>DNA methylation-based subtype prediction for pediatric acute lymphoblastic leukemia
    Visa övriga...
    2015 (Engelska)Ingår i: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 7, artikel-id 11Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background

    We present a method that utilizes DNA methylation profiling for prediction of the cytogenetic subtypes of acute lymphoblastic leukemia (ALL) cells from pediatric ALL patients. The primary aim of our study was to improve risk stratification of ALL patients into treatment groups using DNA methylation as a complement to current diagnostic methods. A secondary aim was to gain insight into the functional role of DNA methylation in ALL.

    Results

    We used the methylation status of ~450,000 CpG sites in 546 well-characterized patients with T-ALL or seven recurrent B-cell precursor ALL subtypes to design and validate sensitive and accurate DNA methylation classifiers. After repeated cross-validation, a final classifier was derived that consisted of only 246 CpG sites. The mean sensitivity and specificity of the classifier across the known subtypes was 0.90 and 0.99, respectively. We then used DNA methylation classification to screen for subtype membership of 210 patients with undefined karyotype (normal or no result) or non-recurrent cytogenetic aberrations (‘other’ subtype). Nearly half (n = 106) of the patients lacking cytogenetic subgrouping displayed highly similar methylation profiles as the patients in the known recurrent groups. We verified the subtype of 20% of the newly classified patients by examination of diagnostic karyotypes, array-based copy number analysis, and detection of fusion genes by quantitative polymerase chain reaction (PCR) and RNA-sequencing (RNA-seq). Using RNA-seq data from ALL patients where cytogenetic subtype and DNA methylation classification did not agree, we discovered several novel fusion genes involving ETV6, RUNX1, and PAX5.

    Conclusions

    Our findings indicate that DNA methylation profiling contributes to the clarification of the heterogeneity in cytogenetically undefined ALL patient groups and could be implemented as a complementary method for diagnosis of ALL. The results of our study provide clues to the origin and development of leukemic transformation. The methylation status of the CpG sites constituting the classifiers also highlight relevant biological characteristics in otherwise unclassified ALL patients.

    Nationell ämneskategori
    Hematologi
    Identifikatorer
    urn:nbn:se:uu:diva-242351 (URN)10.1186/s13148-014-0039-z (DOI)000350260800001 ()25729447 (PubMedID)
    Forskningsfinansiär
    Stiftelsen för strategisk forskning (SSF), RBc08-008
    Anmärkning

    De två sista författarna delar sistaförfattarskapet.

    Tillgänglig från: 2015-01-25 Skapad: 2015-01-25 Senast uppdaterad: 2019-10-23Bibliografiskt granskad
    4. DNA methylation-based prediction of in vitro drug resistance in primary pediatric acute lymphoblastic leukemia patient samples
    Öppna denna publikation i ny flik eller fönster >>DNA methylation-based prediction of in vitro drug resistance in primary pediatric acute lymphoblastic leukemia patient samples
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Cancer och onkologi Hematologi Bioinformatik (beräkningsbiologi)
    Identifikatorer
    urn:nbn:se:uu:diva-242543 (URN)
    Forskningsfinansiär
    Stiftelsen för strategisk forskning (SSF), RBc08-008
    Tillgänglig från: 2015-01-27 Skapad: 2015-01-27 Senast uppdaterad: 2018-01-11
    5. Bayesian model averaging of adaptive bandwidth kernel density estimators yields state-of-the-art performance
    Öppna denna publikation i ny flik eller fönster >>Bayesian model averaging of adaptive bandwidth kernel density estimators yields state-of-the-art performance
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nyckelord
    Variable kernel density estimation, adaptive kernel density estimation, Bayesian model averaging, variable bandwidth, square root law
    Nationell ämneskategori
    Sannolikhetsteori och statistik
    Identifikatorer
    urn:nbn:se:uu:diva-242354 (URN)
    Forskningsfinansiär
    Stiftelsen för strategisk forskning (SSF), RBc08-008EU, FP7, Sjunde ramprogrammet, PROACTIVE
    Tillgänglig från: 2015-01-27 Skapad: 2015-01-25 Senast uppdaterad: 2015-03-11
  • 264.
    Bäcklin, Christofer
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Freyhult, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Frost, Britt-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Palle, Josefine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Larsson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Lönnerholm, Gudmar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Gustafsson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    DNA methylation-based prediction of in vitro drug resistance in primary pediatric acute lymphoblastic leukemia patient samplesManuskript (preprint) (Övrigt vetenskapligt)
  • 265.
    Börjeson, Sussanne
    et al.
    Linköpings universitet.
    Johansson, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Psykosocial onkologi och stödjande vård.
    Onkologisk omvårdnad2008Ingår i: Onkologi / [ed] Ulrik Ringborg, Roger Henriksson & Tina Dalianis, Stockholm: Liber, 2008, 2. uppl., s. 232-242Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • 266.
    Börjesson, Susanne
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Livsstil och rehabilitering vid långvarig sjukdom. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Nordin, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Livsstil och rehabilitering vid långvarig sjukdom.
    Fjällskog, Marie-Louise
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Rissanen, Ritva
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden.
    Peterson, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Arving, Cecilia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Livsstil och rehabilitering vid långvarig sjukdom.
    Colored body images reveal the perceived intensity anddistribution of pain in women with breast cancer treated with adjuvant taxanes:: a prospective multi-method study of pain experience2018Ingår i: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, s. 581-591Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Background and aims:

    Breast cancer is the most prevalent adult cancer worldwide. A broader use of screening for early detection and adjuvant systemic therapy with chemotherapy has resulted in improved survival rates. Taxane-containing chemotherapy is one of the cornerstones of the treatment. However, taxane-containing chemotherapy may result in acute chemotherapy-induced nociceptive and neuropathic pain. Since this pain may be an additional burden for the patient both during and after taxane chemotherapy, it is important to rapidly discover and treat it. There is yet no gold standard for assessing taxane-induced pain. In the clinic, applying multiple methods for collecting information on pain may better describe the patients’ pain experiences. The aim was to document the pain during and after taxane through the contribution of different methods for collecting information on taxane-induced pain. Fifty-three women scheduled for adjuvant sequential chemotherapy at doses of ≥75 mg/m2 of docetaxel and epirubicin were enrolled in the study.

    Methods:

    Prospective pain assessments were done on a visual analog scale (VAS) before and during each cycle of treatment for about 5 months, and using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire’s (EORTC-QLQ-C30) two pain questions at baseline, 3 months, and 12 months. Participants scoring pain on the VAS >30 and undergoing an interview also colored their pain on a body image during treatment and at 12 months.

    Results:

    Surprisingly widespread, intense pain was detected using a multi-method approach. The colored body image showed pain being perceived on 51% of the body surface area during treatment, and on 18% 12 months after inclusion. In general, the pain started and peaked in intensity after the first cycle of taxane. After Cycle 3, most women reported an increase in pain on the VAS. Some women continued to report some pain even during the epirubicin cycles. The VAS scores dropped after the last chemotherapy cycle, but not to the baseline level. At baseline, 3 months and 12 months after inclusion, the women who estimated VAS >30 reported higher levels of pain on the pain questions of the EORTC-QLQ-C30.

    Conclusions:

    This study contributes information on how different pain assessment tools offer different information in the assessment of pain. The colored body image brings another dimension to pain diagnostics, providing additional information on the involved body areas and the pain intensities as experienced by the women. A multi-method approach to assessing pain offers many advantages. The timing of the assessment is important to properly assess pain.

    Implications:

    Pain relief needs to be included in the chemotherapy treatment, with individual assessment and treatment of pain, in the same way as is done in chemotherapy-triggered nausea. There is a time window whereby the risk of pain development is at its highest within 24–48 h after receiving taxane chemotherapy. Proper attention to pain evaluation and treatment should be in focus during this time window.

  • 267. Cadenas, Cristina
    et al.
    Vosbeck, Sonja
    Edlund, Karolina
    Grgas, Katharina
    Madjar, Katrin
    Hellwig, Birte
    Adawy, Alshaimaa
    Glotzbach, Annika
    Stewart, Joanna D.
    Lesjak, Michaela S.
    Franckenstein, Dennis
    Claus, Maren
    Hayen, Heiko
    Schriewer, Alexander
    Gianmoena, Kathrin
    Thaler, Sonja
    Schmidt, Marcus
    Micke, Patrick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Pontén, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Mardinoglu, Adil
    Zhang, Cheng
    Käfferlein, Heiko U.
    Watzl, Carsten
    Frank, Saša
    Rahnenführer, Jörg
    Marchan, Rosemarie
    Hengstler, Jan G.
    LIPG-promoted lipid storage mediates adaptation to oxidative stress in breast cancer2019Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 145, nr 4, s. 901-915Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Endothelial lipase (LIPG) is a cell surface associated lipase that displays phospholipase A1 activity towards phosphatidylcholine present in high‐density lipoproteins (HDL). LIPG was recently reported to be expressed in breast cancer and to support proliferation, tumourigenicity and metastasis. Here we show that severe oxidative stress leading to AMPK activation triggers LIPG upregulation, resulting in intracellular lipid droplet accumulation in breast cancer cells, which supports survival. Neutralizing oxidative stress abrogated LIPG upregulation and the concomitant lipid storage. In human breast cancer, high LIPG expression was observed in a limited subset of tumours and was significantly associated with shorter metastasis‐free survival in node‐negative, untreated patients. Moreover, expression of PLIN2 and TXNRD1 in these tumours indicated a link to lipid storage and oxidative stress. Altogether, our findings reveal a previously unrecognized role for LIPG in enabling oxidative stress‐induced lipid droplet accumulation in tumour cells that protects against oxidative stress, and thus supports tumour progression.

  • 268.
    Caja, Laia Puigsubira
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bellomo, Claudia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Moustakas, Aristidis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Transforming growth factor beta and bone morphogenetic protein actions in brain tumors2015Ingår i: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 589, nr 14, s. 1588-1597Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Members of the transforming growth factor beta (TGF-beta) family are implicated in the biology of several cancers. Here we focus on malignancies of the brain and examine the TGF beta and the bone morphogenetic protein (BMP) signaling branches of the family. These pathways exhibit context-dependent actions during tumorigenesis, acting either as tumor suppressors or as pro-tumorigenic agents. In the brain, the TGF-beta s associate with oncogenic development and progression to the more malignant state. Inversely, the BMPs suppress tumorigenic potential by acting as agents that induce tumor cell differentiation. The latter has been best demonstrated in grade IV astrocytomas, otherwise known as glioblastoma multiforme. We discuss how the actions of TGF-beta s and BMPs on cancer stem cells may explain their effects on tumor progression, and try to highlight intricate mechanisms that may link tumor cell differentiation to invasion. The focus on TGF-beta and BMP and their actions in brain malignancies provides a rich territory for mechanistic understanding of tumor heterogeneity and suggests ways for improved therapeutic intervention, currently being addressed by clinical trials.

  • 269.
    Cajander, Åsa
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Bildanalys och människa-datorinteraktion.
    Grünloh, Christiane
    Moll, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Bildanalys och människa-datorinteraktion.
    Using data for better cancer treatments2018Ingår i: Care for Cancer, Uppsala University, 2018, s. 34-37Konferensbidrag (Övrigt vetenskapligt)
  • 270. Caplin, M. E.
    et al.
    Baudin, E.
    Ferolla, P.
    Filosso, P.
    Garcia-Yuste, M.
    Lim, E.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Pelosi, G.
    Perren, A.
    Rossi, R. E.
    Travis, W. D.
    Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids2015Ingår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 26, nr 8, s. 1604-1620Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management. Patients and methods: Bibliographical searches were carried out in PubMed for the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'pulmonary typical/atypical carcinoid', and 'pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis'. A systematic review of the relevant literature was carried out, followed by expert review. Results: PCs are well-differentiated neuroendocrine tumors and include low-and intermediate-grade malignant tumors, i.e. typical (TC) and atypical carcinoid (AC), respectively. Contrast CT scan is the diagnostic gold standard for PCs, but pathology examination is mandatory for their correct classification. Somatostatin receptor imaging may visualize nearly 80% of the primary tumors and is most sensitive for metastatic disease. Plasma chromogranin A can be increased in PCs. Surgery is the treatment of choice for PCs with the aim of removing the tumor and preserving as much lung tissue as possible. Resection of metastases should be considered whenever possible with curative intent. Somatostatin analogs are the first-line treatment of carcinoid syndrome and may be considered as first-line systemic antiproliferative treatment in unresectable PCs, particularly of low-grade TC and AC. Locoregional or radiotargeted therapies should be considered for metastatic disease. Systemic chemotherapy is used for progressive PCs, although cytotoxic regimens have demonstrated limited effects with etoposide and platinum combination the most commonly used, however, temozolomide has shown most clinical benefit. Conclusions: PCs are complex tumors which require a multidisciplinary approach and long-term follow-up.

  • 271.
    Carde, Patrice
    et al.
    Gustave Roussy Canc Campus, F-94805 Villejuif, France..
    Karrasch, Matthias
    European Org Res & Treatment, Canc Headquarters, Brussels, Belgium..
    Fortpied, Catherine
    European Org Res & Treatment, Canc Headquarters, Brussels, Belgium..
    Brice, Pauline
    Hop St Louis, Paris, France..
    Khaled, Hussein
    Natl Canc Inst, Cairo, Egypt..
    Casasnovas, Olivier
    Ctr Hosp Univ CHU Dijon, Dijon, France..
    Caillot, Denis
    Ctr Hosp Univ CHU Dijon, Dijon, France..
    Gaillard, Isabelle
    CHU Henri Mondor, F-94010 Creteil, France..
    Bologna, Serge
    Ctr Hosp Reg Univ CHR Nancy, Nancy, France..
    Ferme, Christophe
    Gustave Roussy Canc Campus, F-94805 Villejuif, France..
    Lugtenburg, Pieternella Johanna
    Erasmus MC, Inst Canc, Rotterdam, Netherlands..
    Morschhauser, Frank
    CHR Lille, Lille, France..
    Aurer, Igor
    Univ Hosp Ctr Zagreb, Zagreb, Croatia..
    Coiffier, Bertrand
    CHU Lyon, Lyon, France..
    Meyer, Ralph
    Juravinski Canc Ctr, Hamilton, ON, Canada..
    Seftel, Matthew
    Canc Care Manitoba, Winnipeg, MB, Canada..
    Wolf, Max
    Peter MacCallum Canc Inst, East Melbourne, Vic, Australia..
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Sureda, Anna
    Hosp Santa Creu & Sant Pau, Barcelona, Spain..
    Mounier, Nicolas
    Hop Archet, Nice, France..
    Eight Cycles of ABVD Versus Four Cycles of BEACOPP(escalated) Plus Four Cycles of BEACOPP(baseline) in Stage III to IV, International Prognostic Score >= 3, High-Risk Hodgkin Lymphoma: First Results of the Phase III EORTC 20012 Intergroup Trial2016Ingår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 34, nr 17, s. 2028-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose To compare patients with high-risk stage III to IV Hodgkin lymphoma (HL) in the phase III European Organisation for Research and Treatment of Cancer 20012 Intergroup trial (Comparison of Two Combination Chemotherapy Regimens in Treating Patients With Stage III or Stage IV Hodgkin's Lymphoma) who were randomly assigned to either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or to bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP). Patients and Methods Patients with clinical stage III or IV HL, International Prognostic Score of 3 or higher, and age 60 years or younger received ABVD for eight cycles (ABVD(8)) or escalated-dose BEACOPP (BEACOPP(escalated)) for four cycles followed by baseline BEACOPP (BEACOPP(baseline)) for four cycles (BEACOPP(4+4)) without radiotherapy. Primary end points were event-free survival (EFS), treatment discontinuation, no complete response (CR) or unconfirmed complete response (CRu) after eight cycles, progression, relapse, or death. Secondary end points were CR rate, overall survival (OS), quality of life, secondary malignancies, and disease-free survival in CR/CRu patients. Results Between 2002 and 2010, 549 patients were randomly assigned to ABVD(8) (n = 275) or BEACOPP(4+4) (n = 274). Other characteristics included median age, 35 years; male, 75%; stage IV, 74%; "B" symptoms, 81%; and International Prognostic Score >= 4, 59%. WHO performance status was 0 (34%), 1 (48%), or 2 (17%). Median follow-upwas 3.6 years. CR/CRu was 82.5% in both arms. At 4 years, EFS was 63.7% for ABVD(8) versus 69.3% for BEACOPP(4+4) (hazard ratio [HR], 0.86; 95% CI, 0.64 to 1.15; P = .312); disease-free survival was 85.8% versus 91.0% (HR, 0.59; 95% CI, 0.33 to 1.06; P = .076), and OS was 86.7% versus 90.3% (HR, 0.71; 95% CI, 0.42 to 1.21; P = .208). Death as a result of toxicity occurred in six and five patients, early discontinuation (before cycle 5) in 12 and 26 patients, treatment crossovers in five and 10 patients, and secondary malignancies in eight and 10 patients in the ABVD(8) and BEACOPP(4+4) arms, respectively. Conclusion ABVD(8) and BEACOPP(4+4) resulted in similar EFS and OS in patients with high-risk advanced-stage HL. Because BEACOPP(4+4) did not demonstrate a favorable effectiveness or toxicity ratio compared with ABVD(8), treatment burden, immediate and late toxicities, and associated costs must be considered before selecting one of these regimens on which to build future treatment strategies.

  • 272.
    Carde, Patrice P.
    et al.
    Gustave Roussy Canc Campus, Villejuif, France..
    Grynberg, Michael
    Hop Jean Verdier, Bondy, France..
    Poirot, Catherine
    Hop St Louis, Paris, France..
    Glimelius, Bengt
    Univ Uppsala Hosp, Uppsala, Sweden..
    Mounier, Nicolas
    LArchet Hosp, Nice, France..
    How Relevant Is Treatment-Related Infertility for Individual Treatment Selection in Hodgkin Lymphoma?: Reply2017Ingår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 35, nr 3, s. 374-+Artikel i tidskrift (Refereegranskat)
  • 273.
    Carlbom, Lina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Caballero-Corbalán, José
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Transplantation och regenerativ medicin.
    Granberg, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sörensen, Jens
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Whole-body MRI including diffusion-weighted MRI compared with 5-HTP PET/CT in the detection of neuroendocrine tumors2017Ingår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, nr 1, s. 43-50Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: We wanted to explore if whole-body magnetic resonance imaging (MRI) including diffusion-weighted (DW) and liver-specific contrast agent-enhanced imaging could be valuable in lesion detection of neuroendocrine tumors (NET). [11C]-5-Hydroxytryptophan positron emission tomography/computed tomography (5-HTP PET/CT) was used for comparison.

    MATERIALS AND METHODS: Twenty-one patients with NET were investigated with whole-body MRI, including DW imaging (DWI) and contrast-enhanced imaging of the liver, and whole-body 5-HTP PET/CT. Seven additional patients underwent upper abdomen MRI including DWI, liver-specific contrast agent-enhanced imaging, and 5-HTP PET/CT.

    RESULTS: There was a patient-based concordance of 61% and a lesion-based concordance of 53% between the modalities. MRI showed good concordance with PET in detecting bone metastases but was less sensitive in detecting metastases in mediastinal lymph nodes. MRI detected more liver metastases than 5-HTP PET/CT.

    CONCLUSION: Whole-body MRI with DWI did not detect all NET lesions found with whole-body 5-HTP PET/CT. Our findings indicate that MRI of the liver including liver-specific contrast agent-enhanced imaging and DWI could be a useful complement to whole-body 5-HTP PET/CT.

  • 274.
    Carlier, Charlotte
    et al.
    Univ Ghent, Dept Surg, Expt Surg Lab, Ghent, Belgium..
    Strese, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Viktorsson, Kristina
    Karolinska Inst, Dept Pathol & Oncol, Karolinska Biom Ctr, Stockholm, Sweden..
    Velander, Ebba
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Uustalu, Maria
    Oncopeptides AB, Stockholm, Sweden..
    Juntti, Therese
    Karolinska Inst, Dept Pathol & Oncol, Karolinska Biom Ctr, Stockholm, Sweden.;Oncopeptides AB, Stockholm, Sweden..
    Lewensohn, Rolf
    Karolinska Inst, Dept Pathol & Oncol, Karolinska Biom Ctr, Stockholm, Sweden..
    Larsson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin.
    Spira, Jack
    InSpira Med AB, Tyreso, Sweden..
    De Vlieghere, Elly
    Univ Ghent, Lab Expt Canc Res, Radiat Oncol & Expt Canc Res, Ghent, Belgium..
    Ceelen, Wim P.
    Univ Ghent, Dept Surg, Expt Surg Lab, Ghent, Belgium..
    Gullbo, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Preclinical activity of melflufen (J1) in ovarian cancer2016Ingår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, nr 37, s. 59322-59335Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Ovarian cancer carries a significant mortality. Since symptoms tend to be minimal, the disease is often diagnosed when peritoneal metastases are already present. The standard of care in advanced ovarian cancer consists of platinum-based chemotherapy combined with cytoreductive surgery. Unfortunately, even after optimal cytoreduction and adjuvant chemotherapy, most patients with stage III disease will develop a recurrence. Intraperitoneal administration of chemotherapy is an alternative treatment for patients with localized disease. The pharmacological and physiochemical properties of melflufen, a peptidase potentiated alkylator, raised the hypothesis that this drug could be useful in ovarian cancer and particularily against peritoneal carcinomatosis. In this study the preclinical effects of melflufen were investigated in different ovarian cancer models. Melflufen was active against ovarian cancer cell lines, primary cultures of patient-derived ovarian cancer cells, and inhibited the growth of subcutaneous A2780 ovarian cancer xenografts alone and when combined with gemcitabine or liposomal doxorubicin when administered intravenously. In addition, an intra-and subperitoneal xenograft model showed activity of intraperitoneal administered melflufen for peritoneal carcinomatosis, with minimal side effects and modest systemic exposure. In conclusion, results from this study support further investigations of melflufen for the treatment of peritoneal carcinomatosis from ovarian cancer, both for intravenous and intraperitoneal administration.

  • 275.
    Carlsen, Esben Andreas
    et al.
    Rigshosp, Dept Clin Physiol Nucl Med & PET, Copenhagen, Denmark;Univ Copenhagen, Dept Biomed Sci, Cluster Mol Imaging, Copenhagen, Denmark.
    Fazio, Nicola
    European Inst Oncol IRCCS, Div Gastrointestinal Med Oncol & Neuroendocrine T, IEO, Milan, Italy.
    Granberg, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Grozinsky-Glasberg, Simona
    Hadassah Hebrew Univ, Dept Endocrinol & Metab, Neuroendocrine Tumor Unit, Med Ctr, Jerusalem, Israel.
    Ahmadzadehfar, Hojjat
    Univ Hosp Bonn, Dept Nucl Med, Bonn, Germany.
    Grana, Chiara Maria
    European Inst Oncol IRCCS, Div Nucl Med, IEO, Milan, Italy.
    Zandee, Wouter T.
    Erasmus MC, Rotterdam, Netherlands.
    Cwikla, Jaroslaw
    Univ Warmia & Mazury, Med Sch, Olsztyn, Poland.
    Walter, Martin A.
    Univ Hosp Geneva, Dept Nucl Med, Geneva, Switzerland.
    Oturai, Peter Sandor
    Rigshosp, Dept Clin Physiol Nucl Med & PET, Copenhagen, Denmark.
    Rinke, Anja
    Univ Hosp Giess & Marburg, Dept Gastroenterol, Marburg, Germany.
    Weaver, Andrew
    Churchill Hosp, Dept Oncol, Oxford, England.
    Frilling, Andrea
    Imperial Coll London, Dept Surg & Canc, London, England.
    Gritti, Sara
    European Inst Oncol IRCCS, Div Gastrointestinal Med Oncol & Neuroendocrine T, IEO, Milan, Italy.
    Arveschoug, Anne Kirstine
    Aarhus Univ Hosp, Dept Nucl Med & PET, Aarhus, Denmark.
    Meirovitz, Amichay
    Hadassah Hebrew Univ, Med Ctr, Dept Oncol, Jerusalem, Israel;Hadassah Hebrew Univ, Med Ctr, Radiat Therapy Unit, Jerusalem, Israel.
    Knigge, Ulrich
    Univ Copenhagen, Dept Biomed Sci, Cluster Mol Imaging, Copenhagen, Denmark;Rigshosp, Dept Surg Gastroenterol, Copenhagen, Denmark;Rigshosp, Dept Clin Endocrinol, Copenhagen, Denmark.
    Sorbye, Halfdan
    Haukeland Hosp, Dept Oncol, Bergen, Norway;Univ Bergen, Dept Clin Sci, Bergen, Norway.
    Peptide receptor radionuclide therapy in gastroenteropancreatic NEN G3: a multicenter cohort study2019Ingår i: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 26, nr 2, s. 227-239Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Peptide receptor radionuclide therapy (PRRT) is an established treatment of metastatic neuroendocrine tumors grade 1-2 (G1-G2). However, its possible benefit in high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN G3) is largely unknown. We therefore aimed to assess the benefits and side effects of PRRT in patients with GEP NEN G3. We performed a retrospective cohort study at 12 centers to assess the efficacy and toxicity of PRRT in patients with GEP NEN G3. Outcomes were response rate, disease control rate, progression-free survival (PFS), overall survival (OS) and toxicity. We included 149 patients (primary tumor: pancreatic n = 89, gastrointestinal n = 34, unknown n = 26). PRRT was first-line (n = 30), second-line (n = 62) or later-line treatment (n = 57). Of 114 patients evaluated, 1% had complete response, 41% partial response, 38% stable disease and 20% progressive disease. Of 104 patients with documented progressive disease before PRRT, disease control rate was 69%. The total cohort had median PFS of 14 months and OS of 29 months. Ki-67 21-54% (n = 125) vs Ki-67 >= 55% (n = 23): PFS 16 vs 6 months (P < 0.001) and OS 31 vs 9 months (P < 0.001). Well (n = 60) vs poorly differentiated NEN (n = 62): PFS 19 vs 8 months (P < 0.001) and OS 44 vs 19 months (P < 0.001). Grade 3-4 hematological or renal toxicity occurred in 17% of patients. This large multicenter cohort of patients with GEP NEN G3 treated with PRRT demonstrates promising response rates, disease control rates, PFS and OS as well as toxicity in patients with mainly progressive disease. Based on these results, PRRT may be considered for patients with GEP NEN G3.

  • 276. Carlsson, G.
    et al.
    Boxhammer, S.
    Garwicz, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Henter, J. I.
    Palmblad, J.
    Nordenskjöld, M.
    Porwit, A.
    Fadeel, Bengt
    Survivin expression in the bone marrow of patients with severe congenital neutropenia2009Ingår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 23, nr 3, s. 622-625Artikel i tidskrift (Refereegranskat)
  • 277.
    Carlsson, Jorgen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Imaging ff HER2-Expression in Breast Cancer Metastases (Review)2014Ingår i: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 34, nr 10, s. 5855-5855Artikel i tidskrift (Övrigt vetenskapligt)
  • 278.
    Carlsson, Jörgen
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Wester, Kenneth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    De La Torre, Manuel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Gardmark, Truls
    EGFR-expression in primary urinary bladder cancer and corresponding metastases and the relation to HER2-expression. On the possibility to target these receptors with radionuclides2015Ingår i: Radiology and Oncology, ISSN 1318-2099, E-ISSN 1581-3207, Vol. 49, nr 1, s. 50-58Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. There is limited effect of tyrosine kinase inhibitors or "naked" antibodies binding EGFR or HER2 for therapy of metastasized urinary bladder canter and these methods are therefore not routinely used. Targeting radionuclides to the extracellular domain of the receptors is potentially a better possibility. Methods. EGFR- and HER2-expression was analyzed for primary tumors and corresponding metastases from 72 patients using immunohistochemistry and the internationally recommended HercepTest. Intracellular mutations were not analyzed since only the receptors were considered as targets and intracellular abnormalities should have minor effect on radiation dose. Results. EGFR was positive in 71% of the primary tumors and 69% of corresponding metastases. Local and distant metastases were EGFR-positive in 75% and 66% of the cases, respectively. The expression frequency of HER2 in related lesions was slightly higher (data from previous study). The EGFR-positive tumors expressed EGFR in metastases in 86% of the cases. The co-expression of EGFR and HER2 was 57% for tumors and 53% for metastases. Only 3% and 10% of the lesions were negative for both receptors in tumors and metastases, respectively. Thus, targeting these receptors with radionuclides might be applied for most patients. Conclusions. At least one of the EGFR- or HER2-receptors was present in most cases and co-expressed in more than half the cases. It is therefore interesting to deliver radionuclides for whole-body receptor-analysis, dosimetry and therapy. This can hopefully compensate for resistance to other therapies and more patients can hopefully be treated with curative instead of palliative intention.

  • 279.
    Carlsson, Maria
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Informational support for patients with gynaecological cancer and their families1997Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The main purpose of the present thesis was to gain a deeper knowledge and understanding of the informational need by women with gynaecological cancer and their families. The studies evaluate the experience of different kind of information giving; a telephone-help line; a 3 years educational group support programme; and information givings in ordinary care.

    There was a significant correlation to interest in an educational supportive group in the prestudy depending on age, legal status, educational level. Younger individuals, couples and people with a higher formal education were generally more interesting in participating (p<0.05). Patients who actively chose to participate m a an educational support group differed from the unselected control group even prior the intervention, they with a higher formal education were generally more interesting in participating, they felt more confused and angry than the control group. After intervention, the patients in the interventional group reported a significant improved level of knowledge about cancer.

    Both patients and next-of-kin request information about medical- and psychological aspects of the disease and its treatment. The evaluation of the questions in the educational supportive group show that patients and their relatives asked questions of a general nature, related to basic knowledge of cancer and treatment principles, and not directly related to their own illness. There was no general difference in knowledge level between cancer patients and the controls of healthy women. The length of formal education was the most important determinator of correct answers (p<0.01).

    Two main themes were revealed at the interviews about the patients informations preferences. These were to actively address questions and the right to receive honest information;

    It is concluded that differential information giving techniques are required to satisfy the patients' different preferences. The patients express an active role in the information giving process. They preferred information with numerous opportunities to address questions, that the staff have time for questions and that the questions are honestly answered.

  • 280.
    Carlsson, Maria
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Strang, Peter
    Bjurström, Christina
    Treatment modality affects long-term quality of life in gynaecological cancer.2000Ingår i: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 20, nr 1B, s. 563-568Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In order to survey the side effects after cancer treatment, quality of life data were collected from females in clinical remission.

    MATERIALS AND METHODS

    The study was cross-sectional; every patient that visited the outpatient clinic during a period of three months was asked to anonymously complete the EORTC QLQ-C30 questionnaire and five additional specific questions related to gynaecological cancer.

    RESULTS

    In total, 235 patients (90%) returned the questionnaire. In general, both the levels of functioning and symptomatology were time-dependent. Patients with short treatment-free intervals reported more problems than the others. When using treatment modality as an independent variable in the statistical calculations, a treatment-related effect on functioning and symptomatology was demonstrated (p < 0.05 to p < 0.001). Patients previously treated with chemotherapy had poorer role- and cognitive functioning and more problems with fatigue, nausea, vomiting, dyspnoea, constipation and financial problems, compared with those not treated with chemotherapy (p < 0.05 to p < 0.01). Those patients who had been treated with external radiotherapy and/or brachytherapy had significantly more problems with flatulence and diarrhoea (p < 0.05 to p < 0.001). In conclusion, patients who underwent treatment for gynaecological cancer reported long-term side effects also many years after finishing treatment. The problems where related to treatment modality which should be considered, especially when planning adjuvant treatment.

  • 281.
    Carlsson, Sigrid
    et al.
    Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10021 USA.;Univ Gothenburg, Sahlgrenska Acad, Dept Urol, Gothenburg, Sweden..
    Drevin, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Loeb, Stacy
    NYU, New York, NY USA.;Manhattan Vet Affairs Med Ctr, New York, NY USA..
    Widmark, Anders
    Umea Univ, Oncol, Dept Radiat Sci, Umea, Sweden..
    Lissbrant, Ingela Franck
    Univ Gothenburg, Sahlgrenska Acad, Dept Oncol, Gothenburg, Sweden..
    Robinson, David
    Umea Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, S-90185 Umea, Sweden.;Ryhov Cty Hosp, Dept Urol, Jonkoping, Sweden..
    Johansson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Stattin, Par
    Umea Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, S-90185 Umea, Sweden..
    Fransson, Per
    Umea Univ, Dept Nursing, Umea, Sweden..
    Population-based study of long-term functional outcomes after prostate cancer treatment2016Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 117, nr 6B, s. E36-E45Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective To evaluate long-term urinary, sexual and bowel functional outcomes after prostate cancer treatment at a median (interquartile range) follow-up of 12 (11-13) years. Patients and Methods In this nationwide, population-based study, we identified 6 003 men diagnosed with localized prostate cancer (clinical local stage T1-2, any Gleason score, prostate-specific antigen <20 ng/mL, NX or N0, MX or M0) between 1997 and 2002 from the National Prostate Cancer Register, Sweden. The men were aged <= 70 years at diagnosis. A control group of 1 000 men without prostate cancer were also selected, matched for age and county of residence. Functional outcomes were evaluated with a validated self-reported questionnaire. Results Responses were obtained from 3 937/6 003 cases (66%) and 459/1 000 (46%) controls. At 12 years after diagnosis and at a median age of 75 years, the proportion of cases with adverse symptoms was 87% for erectile dysfunction/sexual inactivity, 20% for urinary incontinence and 14% for bowel disturbances. The corresponding proportions for controls were 62, 6 and 7%, respectively. Men with prostate cancer, except those on surveillance, had an increased risk of erectile dysfunction compared with the men in the control group. Radical prostatectomy was associated with an increased risk of urinary incontinence (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.36-2.62) and radiotherapy increased the risk of bowel dysfunction (OR 2.46, 95% CI 1.73-3.49) compared with men in the control group. Multimodal treatment, in particular treatment including androgen deprivation therapy (ADT), was associated with the highest risk of adverse effects; for instance, radical prostatectomy followed by radiotherapy and ADT was associated with an OR of 3.74 (95% CI 1.76-7.95) for erectile dysfunction and an OR of 3.22 (95% CI 1.93-5.37) for urinary incontinence. Conclusion The proportion of men who experienced a long-term impact on functional outcomes after prostate cancer treatment was substantial.

  • 282.
    Carlsson, Tommy
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Klinisk psykologi i hälso- och sjukvård. Sophiahemmet University, Stockholm, Sweden.
    Kukkola, Laura
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Klinisk psykologi i hälso- och sjukvård.
    Ljungman, Lisa
    Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Hovén, Emma
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Klinisk psykologi i hälso- och sjukvård.
    von Essen, Louise
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Klinisk psykologi i hälso- och sjukvård.
    Psychological distress in parents of children treated for cancer: An explorative study2019Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 6, artikel-id e0218860Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective To explore psychological distress experienced by parents who express a need for psychotherapy after curative treatment for their child's cancer. Methods 15 parents (eight mothers and seven fathers) of children treated for cancer (median time since end of curative treatment: two years) were recruited via a pediatric oncology center. Each parent was interviewed twice and data was analyzed with inductive latent qualitative content analysis. Results Two overarching themes emerged. One theme, An unfamiliar and frightening situation during treatment, portrayed experiences during the treatment period, and included the sub-themes Initial reactions to the uncontrollable situation, Adjustment to the situation, and Focus on supporting the child. Another theme, Emotional struggles after end of curative treatment, portrayed experiences following curative treatment, and included the sub-themes Transitioning back to life as it was before the diagnosis, Emotional scars, Uncontrollable fears and worries of diseases, and New perspectives on life. Conclusions Parents of children with cancer experience existential, physical, psychological, and social struggles. They describe an unstable situation after diagnosis and having focused their attention towards protecting their child during treatment. After the end of curative treatment, they experience challenges with transitioning back to life as it was before the diagnosis and dealing with their own emotional scars and fears related to the child's cancer. The findings indicate an unmet need for psychological support among parents of children treated for cancer.

  • 283.
    Carstam, Louise
    et al.
    Sahlgrens Univ Hosp, Dept Neurosurg, Gothenburg, Sweden; Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden.
    Smits, Anja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden.
    Milos, Peter
    Linköping Univ Hosp, Dept Neurosurg, Linköping, Sweden.
    Corell, Alba
    Sahlgrens Univ Hosp, Dept Neurosurg, Gothenburg, Sweden.
    Henriksson, Roger
    Reg Canc Ctr Stockholm Gotland, Stockholm, Sweden; Univ Umeå, Dept Radiat Sci & Oncol, Umeå, Sweden.
    Bartek, Jiri Jr
    Karolinska Univ Hosp, Dept Neurosurg, Stockholm, Sweden; Karolinska Inst, Dept Neurosci, Stockholm, Sweden; Karolinska Inst, Dept Med, Stockholm, Sweden; Copenhagen Univ Hosp, Rigshosp, Dept Neurosurg, Copenhagen, Denmark.
    Jakola, Asgeir Store
    Sahlgrens Univ Hosp, Dept Neurosurg, Gothenburg, Sweden; Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden; St Olavs Univ Hosp HF, Dept Neurosurg, Trondheim, Norway.
    Neurosurgical patterns of care for diffuse low-grade gliomas in Sweden between 2005 and 20152018Ingår i: Neurooncology Practice, ISSN 2054-2577, Vol. 6, nr 2, s. 124-133Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: In the last decade, increasing evidence has evolved for early and maximal safe resection of diffuse low-grade gliomas (LGGs) regarding survival. However, changes in clinical practice are known to occur slowly and we do not know if the scientific evidence has yet resulted in changes in neurosurgical patterns of care.

    Methods: The Swedish Brain Tumor Registry was used to identify all patients with a first-time histopathological diagnosis of LGG between 2005 and 2015. For analysis of surgical treatment patterns, we subdivided assessed time periods into 2005-2008, 2009-2012, and 2013-2015. Population-based data on patient and disease characteristics, surgical management, and outcomes were extracted.

    Results: A total of 548 patients with diffuse World Health Organization grade II gliomas were identified: 142 diagnosed during 2005-2008, 244 during 2009-2012, and 162 during 2013-2015. Resection as opposed to biopsy was performed in 64.3% during 2005-2008, 74.2% during 2009-2012, and 74.1% during 2013-2015 (P = .08). There was no difference among the 3 periods regarding overall survival (P = .11). However, post hoc analysis of data from the 4 (out of 6) centers that covered all 3 time periods demonstrated a resection rate of 64.3% during 2005-2008, 77.4% during 2009-2012, and 75.4% during 2013-2015 (P = .02) and longer survival of patients diagnosed 2009 and onward (P = .04).

    Conclusion: In this nationwide, population-based study we observed a shift over time in favor of LGG resection. Further, a positive correlation between the more active surgical strategy and longer survival is shown, although no causality can be claimed because of possible confounding factors.

  • 284. Carthy, Jon M.
    et al.
    Sundqvist, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Heldin, Angelos
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Van Dam, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Kletsas, Dimitris
    Natl Ctr Sci Res Demokritos, Inst Biosci & Applicat, Lab Cell Proliferat & Ageing, Athens, Greece..
    Heldin, Carl-Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Moustakas, Aristidis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Tamoxifen Inhibits TGF-beta-Mediated Activation of Myofibroblasts by Blocking Non-Smad Signaling Through ERK1/22015Ingår i: Journal of Cellular Physiology, ISSN 0021-9541, E-ISSN 1097-4652, Vol. 230, nr 12, s. 3084-3092Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine which stimulates the differentiation of fibroblasts into myofibroblasts. Myofibroblasts are critical for normal wound healing, but also accumulate pathologically in a number of chronic inflammatory conditions where they are key contributors to aberrant tissue remodeling and fibrosis, and in cancer stroma. In the current study, we identified a role for tamoxifen as a potent inhibitor of the TGF-beta-mediated activation of primary human skin and breast fibroblasts. Our data indicate that tamoxifen does not interfere with canonical Smad signaling downstream of TGF-beta but rather blocks non-Smad signaling through ERK1/2 MAP-kinase and the AP-1 transcription factor FRA2. We further demonstrate by siRNA-mediated knockdown that FRA2 is critical for the induced expression of myogenic proteins in response to TGF-beta. Functionally, TGF-beta-stimulated fibroblast-mediated contraction of collagen gels was impaired in the presence of tamoxifen. Altogether, these data demonstrate that tamoxifen prevents myofibroblast differentiation and, therefore, may provide therapeutic benefits to patients suffering from chronic inflammatory conditions or cancer.

  • 285.
    Casar Borota, Olivera
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Botling, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Granberg, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Stigare, Jerker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Wikström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Boldt, Henning Bünsow
    Kristensen, Bjarne Winther
    Ponten, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Trouillas, Jacqueline
    Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas: Markers in the Differential Diagnosis of Neuroendocrine Tumors of the Sellar Region.2017Ingår i: American Journal of Surgical Pathology, ISSN 0147-5185, E-ISSN 1532-0979, Vol. 41, nr 9, s. 1238-1246Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown. Facing a difficult diagnostic case of an invasive serotonin and adrenocorticotroph hormone immunoreactive NET in the sellar region, we explored the immunohistochemical expression of serotonin, ATRX, and DAXX in a large series of pituitary endocrine tumors of different types from 246 patients and in 2 corticotroph carcinomas. None of the pituitary tumors expressed serotonin, suggesting that serotonin immunoreactive sellar tumors represent primary or secondary NETs of nonpituitary origin. Normal expression of ATRX and DAXX in pituitary tumors suggests that ATRX and DAXX do not play a role in the pathogenesis of pituitary endocrine tumors that remain localized to the sellar and perisellar region. A lack of ATRX or DAXX in a sellar NET suggests a nonpituitary NET, probably of pancreatic origin. One of the 2 examined corticotroph carcinomas, however, demonstrated negative ATRX immunolabeling due to an ATRX gene mutation. Further studies on a larger cohort of pituitary carcinomas are needed to clarify whether ATRX mutations may contribute to the metastatic potential in a subset of pituitary NETs.

  • 286.
    Casar Borota, Olivera
    et al.
    Tromsö University.
    Kloster, Roar
    Lindal, Sigurd
    Carcinoid tumour metastatic to the orbit with infiltration to the extraocular orbital muscle.2005Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 113, nr 2, s. 135-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Ninety-three percent of symptomatic patients with small intestinal carcinoid tumours have metastases. The most common sites of metastases are lymph nodes and liver. Orbital metastases have rarely been described and the majority of them involve the choroid rather than extraocular orbital structures. We report a patient who developed proptosis, impairment of vision and reduced ocular motility on the left side, eighteen months after operation for primary intestinal carcinoid tumour with hepatic metastases. CT and MR studies revealed the tumour mass infiltrating the inferior rectus muscle. Biopsy examined by imprint and frozen section showed tumour consistent with metastatic carcinoid. The tumour was removed. HE and staining for cytokeratin, chromogranin, NSE, serotonin, somatostatin and gastrin showed that the tumour tissue corresponded to that of the primary intestinal carcinoid tumour. Intramuscular orbital metastasis from a carcinoid tumour is a rare occurrence. Diagnosis may be difficult, especially where no evidence of primary carcinoid tumour is present. Metastatic orbital carcinoid should be suspected in patients with a clinical history of carcinoid tumour and who develop ocular complaints and mass lesion in the orbit. Complete surgical removal of the tumour is important for optimal restitution of vision and eye movements.

  • 287.
    Casar-Borota, Olivera
    et al.
    Oslo University.
    Scheie, D
    Bjerkhagen, B
    Jacobsen, E A
    Skullerud, K
    Gliosarcoma with liposarcomatous component, bone infiltration and extracranial growth.2006Ingår i: Clinical Neuropathology, ISSN 0722-5091, Vol. 25, nr 4, s. 200-3Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Gliosarcoma is a highly malignant brain tumor consisting of both a glioblastoma and a mesenchymal component. The latter typically resembles fibrosarcoma, but differentiation patterns resembling osteosarcoma, chondrosarcoma, angiosarcoma and rhabdomyosarcoma have also been described. Molecular-genetic studies have shown that both glioblastoma and the mesenchymal component share identical cytogenetic abnormalities or mutations, suggesting a monoclonal origin from glial cells. We report an unusual case of gliosarcoma that presented as a large intracerebral tumor with infiltration of the temporal bone and the soft tissues in the infratemporal fossa. Microscopically, the tumor consisted of alternating areas of glioblastoma and fibrosarcoma. Focally, areas ofosteosarcomatous and liposarcomatous differentiation were found. Although gliosarcoma with transcranial penetration is very rare, it should be suspected in case of intracranial tumor with glioblastoma-imaging features, infiltration of bone and extracranial growth. Our case of liposarcomatous differentiation in gliosarcoma--together with another very recently reported similar case--expands the morphologic heterogeneity of this peculiar brain tumor.

  • 288.
    Cashin, Peter
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Graf, Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Considerations on the Selection Process for Cytoreductive Surgery and Hyperthermic IntraPeritoneal Chemotherapy for Colorectal Carcinomatosis Reply2015Ingår i: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 262, nr 2, s. e48-e49Artikel i tidskrift (Refereegranskat)
  • 289.
    Cashin, Peter H
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Cytoreductive Surgery and Intraperitoneal Chemotherapy in Patients with Peritoneal Metastases from Colorectal Cancer: Aspects of loco-regional treatment outcome, patient selection, and chemo-sensitivity 2012Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Previously, peritoneal metastases(PM) from colorectal cancer(CRC) have been considered a terminal and generalised form of cancer. A new treatment strategy combining cytoreductive surgery(CRS) and intraperitoneal chemotherapy(IPC) has recently shown promising results. The aim of this thesis was to investigate different aspects of this treatment in order to optimise the treatment and to clarify its potential as a new treatment option. Treatment outcome, patient selection, method of IPC (hyperthermic intraperitoneal chemotherapy-HIPEC vs. sequential postoperative intraperitoneal chemotherapy-SPIC) and choice of drugs for IPC were the aspects covered in this thesis.

    The treatment outcome of CRS and IPC according to the median overall survival ranged from 24 to 34 months with 5-year overall survival ranging from 20 to 40% depending on the IPC treatment administered. Furthermore, the 5-year disease-free survival was impressive at 32% for patients receiving HIPEC. This establishes the curative potential of this treatment. Due to current inadequacies of radiological imaging, a score (Corep score) was developed for patient selection purposes. This score had a sensitivity of 80% and specificity of 100% in identifying patients with short cancer-specific survival after the treatment (<12 months). Further studies are needed to elucidate the clinical usefulness of the Corep score. HIPEC was associated with better survival than the SPIC method at similar morbidity and mortality rates, suggesting that HIPEC be the method of preference. Concerning the choice of drugs, the last study investigated the chemo-sensitivity of different PM tumour-types with a special focus on CRC. While CRC samples were generally more resistant, the ratio of the in vivo concentration compared to the ex vivo concentration giving a 50% tumour cell death showed that oxaliplatin had the best profile across all PM tumour types as well as for CRC. This needs further confirmation in a clinical trial.

    Delarbeten
    1. Cytoreductive Surgery and Intraperitoneal Chemotherapy for Colorectal Peritoneal Carcinomatosis: Prognosis and Treatment of Recurrences in a Cohort Study
    Öppna denna publikation i ny flik eller fönster >>Cytoreductive Surgery and Intraperitoneal Chemotherapy for Colorectal Peritoneal Carcinomatosis: Prognosis and Treatment of Recurrences in a Cohort Study
    2012 (Engelska)Ingår i: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 38, nr 6, s. 509-515Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background

    Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) treatment of colorectal peritoneal carcinomatosis (PC) is gaining acceptance, but controversy remains. The primary aims were to analyze the outcome and prognostic variables of colorectal PC patients treated with CRS and IPC, and to report on the outcome of additional surgical treatments of subsequent recurrences.

    Methods

    Patients referred for treatment of colorectal PC between 1996 and 2010 were included in a cohort. The following data was collected: clinicopathological parameters, survival, recurrences, perioperative chemotherapy and type of IPC (hyperthermic intraperitoneal chemotherapy, HIPEC; or sequential postoperative intraperitoneal chemotherapy, SPIC). Multivariable analyses were conducted on potential prognostic factors for overall survival (OS).

    Results

    In the 151-patient cohort, the median OS was 34months (range: 2-77) for CRS and HIPEC with five-year survival predicted at 40% (five-year disease-free survival 32%). For CRS and SPIC, the OS was 25months (range: 2-188) with five-year survival at 18%.  Open-and-close patients survived 6months (range: 0-14) with no five-year survival (HIPEC vs. SPIC p=0.047, SPIC vs. open-and-close p<0.001). Adjuvant systemic chemotherapy was a noteworthy independent prognostic factor in the multivariable analysis. OS for patients undergoing additional surgical treatment of recurrences was 25months vs. 10months with best supportive care or palliative chemotherapy (p=0.01).

    Conclusion

    Substantial long-term survival is possible in patients with colorectal PC. HIPEC was associated with better OS than SPIC and adjuvant systemic chemotherapy may improve the outcome in patients. Good OS is achievable in selected patients undergoing additional surgical treatment of isolated liver or peritoneal recurrences after prior complete CRS.

    Nyckelord
    HIPEC, Intraperitoneal chemotherapy, Colorectal cancer, Peritoneal carcinomatosis, Cytoreductive surgery, Recurrences
    Nationell ämneskategori
    Kirurgi
    Forskningsämne
    Kirurgi
    Identifikatorer
    urn:nbn:se:uu:diva-169544 (URN)10.1016/j.ejso.2012.03.001 (DOI)000304510600008 ()
    Tillgänglig från: 2012-03-05 Skapad: 2012-03-02 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    2. Patient Selection for Cytoreductive Surgery in Colorectal Peritoneal Carcinomatosis using Serum Tumour Markers – an Observational Cohort Study
    Öppna denna publikation i ny flik eller fönster >>Patient Selection for Cytoreductive Surgery in Colorectal Peritoneal Carcinomatosis using Serum Tumour Markers – an Observational Cohort Study
    2012 (Engelska)Ingår i: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 256, nr 6, s. 1078-1083Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objective: There were 2 objectives: first, to investigate how many patients were excluded from surgery on the basis of the radiological extent of the peritoneal carcinomatosis (PC) or the clinical examination; and second, to develop a score based primarily on serum tumor markers (STMs) that could predict short cancer-specific survival (<12 months). Background: Patient selection and prediction of prognosis is crucial for successful treatment of colorectal PC. Methods: All patients with colorectal PC referred for cytoreductive surgery and intraperitoneal chemotherapy (2005-2008) at Uppsala University hospital were included. Patients were divided into 2 groups-nonsurgery and surgery. Clinicopathological and laboratory parameters were collected in the surgery group. A Corep (COloREctal-Pc) score was developed using hazard ratios from histology, hematological status, serial serum tumor markers (STMs), and STM changes over time. Sensitivity, specificity, positive predicted value (PPV), and negative predicted value (NPV) were calculated in a second validating dataset (n = 24) with a survival cutoff of less than 12 months. Results: A total of 107 patients were included in the study, 42 in the nonsurgery group and 65 in the surgery group. In the nonsurgery group, 2 patients were excluded solely on the basis of the radiological extent of PC and 7 patients on clinical examination. The Corep score ranged from 0 to 18. A score of 6 or more showed a validated sensitivity of 80%, specificity 100%, PPV 1.0, and NPV 0.93. Conclusions: Radiological extent of PC was not a main deciding factor for treatment decisions and had less impact than the clinical examination. The Corep score identified patients with short cancer-specific survival that may not be suitable for treatment.

    Nyckelord
    colorectal cancer, corep score, cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, HIPEC, patient selection, serum tumour markers, peritoneal carcinomatosis, peritoneal metastases
    Nationell ämneskategori
    Kirurgi
    Forskningsämne
    Kirurgi
    Identifikatorer
    urn:nbn:se:uu:diva-169548 (URN)10.1097/SLA.0b013e318254f281 (DOI)000312261000038 ()
    Tillgänglig från: 2012-03-05 Skapad: 2012-03-02 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    3. Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis: a case-control study
    Öppna denna publikation i ny flik eller fönster >>Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis: a case-control study
    2012 (Engelska)Ingår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, nr 3, s. 647-652Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND:

    Cytoreductive surgery and intraperitoneal chemotherapy has improved prognosis in patients with peritoneal carcinomatosis. The main modes of intraperitoneal chemotherapy treatment are peroperative hyperthermic intraperitoneal chemotherapy (HIPEC) and normothermic sequential postoperative intraperitoneal chemotherapy (SPIC). The aim of this study was to compare HIPEC and SPIC with respect to overall survival, disease-free survival, morbidity, and mortality in patients with peritoneal carcinomatosis from colon cancer.

    PATIENTS AND METHODS:

    A matched case-control study was conducted in patients with surgical macroscopic complete removal of carcinomatosis; matching was according to the peritoneal cancer index score. Thirty-two patients were included, 16 in each group (HIPEC and SPIC). Overall survival, disease-free survival, morbidity, mortality, and clinicopathological parameters were compared.

    RESULTS:

    Median overall survival was 36.5 months in the HIPEC group and 23.9 months in the SPIC group (P = 0.01). Median disease-free survival for these groups was 22.8 (HIPEC) and 13.0 months (SPIC; P = 0.02). Morbidity was not statistically different, 19% in SPIC and 37% in HIPEC. Postoperative mortality was observed in one patient in each group.

    CONCLUSION:

    HIPEC was associated with improved overall survival and disease-free survival compared with SPIC at similar morbidity and mortality, suggesting that HIPEC is the treatment of choice in colonic peritoneal carcinomatosis.

    Ort, förlag, år, upplaga, sidor
    Oxford University Press, 2012
    Nationell ämneskategori
    Kirurgi
    Forskningsämne
    Kirurgi
    Identifikatorer
    urn:nbn:se:uu:diva-165543 (URN)10.1093/annonc/mdr301 (DOI)000300733300016 ()21685413 (PubMedID)
    Tillgänglig från: 2012-01-09 Skapad: 2012-01-09 Senast uppdaterad: 2017-12-08Bibliografiskt granskad
    4. Activity ex vivo of cytotoxic drugs in patient samples of peritoneal carcinomatosis with special focus on colorectal cancer
    Öppna denna publikation i ny flik eller fönster >>Activity ex vivo of cytotoxic drugs in patient samples of peritoneal carcinomatosis with special focus on colorectal cancer
    Visa övriga...
    2013 (Engelska)Ingår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 13, s. 435-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: The optimal choice of cytotoxic drugs for intraperitoneal chemotherapy (IPC) in conjunction with cytoreductive surgery (CRS) for treatment of peritoneal carcinomatosis(PC) is poorly defined. We investigated drug sensitivity ex vivo in patient samples of various PC tumor types and correlated clinical outcome to drug sensitivity within the subset of PC fromcolorectal cancer (CRC). 

    Methods: PC tissue samples (n = 174) from mesothelioma, pseudomyxoma peritonei (PMP), ovarian cancer, CRC or appendix cancer were analyzed ex vivo for sensitivity to oxaliplatin, cisplatin, mitomycin C, melphalan, irinotecan, docetaxel, doxorubicin and 5-FU. Clinicopathological variables and outcome data were collected for the CRC subset. 

    Results: Mesothelioma and ovarian cancer were generally more drug sensitive than CRC, appendix cancer and PMP. Oxaliplatin showed the most favorable ratio between achievable IPC concentration and ex vivo drug sensitivity. Drug sensitivity in CRC varied considerably between individual samples. Ex vivo drug sensitivity did not obviously correlate to time-to-progression (TTP) in individual patients. 

    Conclusions: Drug-sensitivity varies considerably between PC diagnoses and individual patients arguing for individualized therapy in IPC rather than standard diagnosis-specific therapy. However, in the current paradigm of treatment according to diagnosis, oxaliplatin is seemingly the preferred drug for IPC from a drug sensitivity and concentration perspective. Inthe CRC subset, analysis of correlation between ex vivo drug sensitivity and TTP was inconclusive due to the heterogeneous nature of the data.

    Nationell ämneskategori
    Cancer och onkologi
    Identifikatorer
    urn:nbn:se:uu:diva-172441 (URN)10.1186/1471-2407-13-435 (DOI)000325079100001 ()
    Tillgänglig från: 2012-04-10 Skapad: 2012-04-10 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
  • 290.
    Cashin, Peter H.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Dranichnikov, Faoz
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Cytoreductive Surgery and Hyperthermic Intra-Peritoneal Chemotherapy Treatment of Colorectal Peritoneal Metastases: Cohort Analysis of High Volume Disease and Cure Rate2014Ingår i: Journal of Surgical Oncology, ISSN 0022-4790, E-ISSN 1096-9098, Vol. 110, nr 2, s. 203-206Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) treatment of colorectal peritoneal metastases (PM) is an established treatment alternative. The study aim was, first, to investigate the outcome of high-volume disease defined by the peritoneal cancer index (PCI) 20; second, to report the long-term disease-free survival of patients with >5 years observation. Methods: Consecutive patients with colorectal PM from a prospective HIPEC database between 2004 and 2010 were included, 67 patients. Clinicopathological and outcome parameters were compared between low PCI (n = 40) and high PCI (n = 27). A subgroup analysis on patients with >5 years observation was performed (n = 32). Disease-free survival after 5 years defined cure. Results: Median overall survival (OS) was 28 months, low PCI-group 33 months versus high PCI-group 17 months (P = 0.03). Median OS of patients with complete CRS (n = 56) was 30 months, low PCI-group 37 months versus high PCI-group 27 months (P = 0.2), with 5-year survival of 31% and 21%, respectively. No difference in morbidity/mortality. The cure rate was 22% in the subgroup (7/32) and 28% in those with complete CRS (7/25). Two patients in the cured group had PCI 29 and 34. Discussion: Treatment of high-volume disease may result in long-term survival and even cure. The key is to reach a complete CRS. The overall cure rate is 22%. 

  • 291.
    Cashin, Peter H
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Graf, Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Karlsson, Henning
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakologi.
    Larsson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakologi.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Activity ex vivo of cytotoxic drugs in patient samples of peritoneal carcinomatosis with special focus on colorectal cancer2013Ingår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 13, s. 435-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The optimal choice of cytotoxic drugs for intraperitoneal chemotherapy (IPC) in conjunction with cytoreductive surgery (CRS) for treatment of peritoneal carcinomatosis(PC) is poorly defined. We investigated drug sensitivity ex vivo in patient samples of various PC tumor types and correlated clinical outcome to drug sensitivity within the subset of PC fromcolorectal cancer (CRC). 

    Methods: PC tissue samples (n = 174) from mesothelioma, pseudomyxoma peritonei (PMP), ovarian cancer, CRC or appendix cancer were analyzed ex vivo for sensitivity to oxaliplatin, cisplatin, mitomycin C, melphalan, irinotecan, docetaxel, doxorubicin and 5-FU. Clinicopathological variables and outcome data were collected for the CRC subset. 

    Results: Mesothelioma and ovarian cancer were generally more drug sensitive than CRC, appendix cancer and PMP. Oxaliplatin showed the most favorable ratio between achievable IPC concentration and ex vivo drug sensitivity. Drug sensitivity in CRC varied considerably between individual samples. Ex vivo drug sensitivity did not obviously correlate to time-to-progression (TTP) in individual patients. 

    Conclusions: Drug-sensitivity varies considerably between PC diagnoses and individual patients arguing for individualized therapy in IPC rather than standard diagnosis-specific therapy. However, in the current paradigm of treatment according to diagnosis, oxaliplatin is seemingly the preferred drug for IPC from a drug sensitivity and concentration perspective. Inthe CRC subset, analysis of correlation between ex vivo drug sensitivity and TTP was inconclusive due to the heterogeneous nature of the data.

  • 292.
    Cashin, Peter H.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Uppsala Canc Clin, Uppsala, Sweden..
    Spang, N.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Syk, I.
    Skane Univ Hosp, Dept Surg, S-21428 Malmo, Sweden..
    Frodin, J. E.
    Karolinska Inst, Dept Pathol & Oncol, S-17176 Stockholm, Sweden..
    Torkzad, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Karolinska Inst, Dept Pathol & Oncol, S-17176 Stockholm, Sweden..
    Graf, Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Cytoreductive surgery and intraperitoneal chemotherapy versus systemic chemotherapy for colorectal peritoneal metastases: A randomised trial2016Ingår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 53, s. 155-162Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: First-line treatment of isolated resectable colorectal peritoneal metastases remains unclear. This study (the Swedish peritoneal study) compares cytoreductive surgery and intraperitoneal chemotherapy (surgery arm) with systemic chemotherapy (chemotherapy arm). Methods: Patients deemed resectable preoperatively were randomised to surgery and intraperitoneal 5-fluorouracil 550 mg/m(2) /d for 6 d with repeated courses every month or to systemic oxaliplatin and 5-fluorouracil regimen every second week. Both treatments continued for 6 months. Primary end-point was overall survival (OS) and secondary end-points were progression-free survival (PFS), and morbidity. Results: The study terminated prematurely when 48 eligible patients (24/arm) were included due to recruitment difficulties. Two-year OS was 54% in the surgery arm and 38% in the chemotherapy arm (p = 0.04). After 5 years, 8 versus 1 patient were alive, respectively (p = 0.02). Median OS was 25 months versus 18 months, respectively, hazard ratio 0.51 (95% confidence interval: 0.27-0.96, p = 0.04). PFS in the surgery arm was 12 months versus 11 months in the chemotherapy arm (p = 0.16) with 17% versus 0% 5-year PFS. Grade III-IV morbidity was seen in 42% and 50% of the patients, respectively. No mortalities. Conclusions: Cytoreductive surgery with intraperitoneal chemotherapy may be superior to systemic oxaliplatin-based treatment of colorectal cancer with resectable isolated peritoneal metastases.(ClinicalTrials. gov nr: NCT01524094).

  • 293.
    Cashin, Peter
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi. Uppsala Canc Clin, Uppsala, Sweden.
    Syk, I.
    Lund Univ, Sect Surg, Dept Clin Sci, Malmo, Sweden.
    Frodin, J. E.
    Karolinska Inst, Dept Oncol & Pathol, S-17176 Stockholm, Sweden.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Karolinska Inst, Dept Oncol & Pathol, S-17176 Stockholm, Sweden.
    Graf, Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Quality of life and cost effectiveness in a randomized trial of patients with colorectal cancer and peritoneal metastases2018Ingår i: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 44, nr 7, s. 983-990Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The aim was to compare health-related quality-of-life (HRQOL) and cost-effectiveness between cytoreductive surgery with intraperitoneal chemotherapy (CRS + IPC) and systemic chemotherapy for patients with colorectal peritoneal metastases. Methods: Patients included in the Swedish Peritoneal Trial comparing CRS + IPC and systemic chemotherapy completed the EORTC QLQ-C30 and SF-36 questionnaires at baseline, 2, 4, 6, 12, 18, and 24 months. HRQOL at 24 months was the primary endpoint. EORTC sum score, SF-36 physical and mental component scores at 24 months were calculated and compared for each arm and then referenced against general population values. Two quality-adjusted life-year (QALY) indices were applied (EORTC-8D and SF-6D) and an incremental cost-effectiveness ratio (ICER) per QALY gained was calculated. A projected life-time ICER per QALY gained was calculated using predicted survival according to Swedish population statistics. Results: No statistical differences in HRQOL between the arms were noted at 24 months. Descriptively, survivors in the surgery arm had higher summary scores than the general population at 24 months, whereas survivors in the chemotherapy arm had lower scores. The projected life-time QALY benefit was 3.8 QALYs in favor of the surgery arm (p=0.06) with an ICER per QALY gained at 310,000 SEK (EORTC-8D) or 362,000 SEK (SF-6D) corresponding to 26,700-31,200 GBP. Conclusion: The HRQOL in patients with colorectal peritoneal metastases undergoing CRS + IPC appear similar to those receiving systemic chemotherapy. Two-year survivors in the CRS + IPC arm have comparable HRQOL to a general population reference. The treatment is cost-effective according to NICE guidelines.

  • 294. Castano, J. P.
    et al.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Maecke, H. R.
    Villabona, C.
    Vazquez-Albertino, R.
    Navarro, E.
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Gastrointestinal neuroendocrine tumors (NETs): new diagnostic and therapeutic challenges2014Ingår i: Cancer Metastasis Review, ISSN 0167-7659, E-ISSN 1573-7233, Vol. 33, nr 1, s. 353-359Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    This paper summarizes the current understanding of the biology of somatostatin receptor (sst), role of immunotherapy in neuroendocrine tumor (NET), new agents for PPRT, and methods to assess response and clinical benefit in NET. One of the most interesting aspects of sst biology is the recent discovery of truncated variants of the sst5 receptor subtype with unique tissue distribution and response to somatostatin (SST). These truncated receptors are associated with bad patient prognosis, decreased response to SST analogs, and may be new targets for diagnoses and treatment. IFN remains a cost-effective agent, particularly in classic mid gut carcinoids, and there is interest to continue examining immunotherapy's in this disease. PRRT remains a key strategy for treatment and imaging. In addition to the classic agents, there are a series of new agents targeting other receptors such as the incretin receptors (GLP-1R; GIPR) and other G-protein coupled receptors with great potential. With regards to therapy monitoring, the most commonly used criteria are Response Criteria Evaluation in Solid Tumors (RECIST). However, for different reasons, these criteria are not very useful in NET. Incorporation of other criteria such as Choi as well as functional imaging assessment with PET would be of great interest in this area.

  • 295.
    Cavalli-Björkman, Nina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Factors Influencing Selection of Treatment for Colorectal Cancer Patients2012Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    In Sweden and elsewhere there is evidence of poorer cancer survival for patients of low socioeconomic status (SES), and in some settings differences in treatment by SES have been shown.

    The aim of this thesis was to explore factors which influence cancer treatment decisions, such as knowledge reaped from clinical trials, patient-related factors, and physician-related factors. In a register study of colorectal cancer, all stages, patients were stratified for SES-factors. Differences were seen with regards to clinical investigation, surgical and oncological treatment and survival, with the highly educated group being favored. Survival was better for highly educated patients in stages I, II and III but not in stage IV.

    In a Scandinavian cohort of newly metastasized colorectal cancer patients, recruitment to clinical trials was studied. Patients entering clinical trials had better performance status and fewer cancer symptoms than those who were treated with chemotherapy outside of a clinical trial. Median survival was 21.3 months for trial-patients and 15.2 months for those treated with chemotherapy outside a  trial. Those not treated with chemotherapy had a median survival of just 2.1 months. Patients in clinical trials are highly selected and conclusions drawn from studies cannot be applied to all patients.

    In the same cohort, treatment and survival were stratified for education, smoking and indicators of social structure. Highly educated patients did not have a survival advantage. Patients who lived alone were offered less combination chemotherapy and surgery of metastases than other patients and had 4 months shorter survival than those who lived with a spouse or child. In a fourth study, 20 Swedish gastrointestinal oncologists were interviewed on which factors they considered when deciding on oncological treatment. Oncologists feared chemotherapy complications due to lack of social support, and ordered less combination chemotherapy for patients living alone. Highly educated patients were seen as well-read and demanding, and giving in to these patients’ requests for treatment was regarded as a way of pleasing patients and relatives and of avoiding conflict.

    Delarbeten
    1.
    Posten kunde inte hittas. Det kan bero på att posten inte längre är tillgänglig eller att du har råkat ange ett felaktigt id i adressfältet.
    2. Clinical trial enrollment, patient characteristics, and survival differences in prospectively registered metastatic colorectal cancer patients
    Öppna denna publikation i ny flik eller fönster >>Clinical trial enrollment, patient characteristics, and survival differences in prospectively registered metastatic colorectal cancer patients
    Visa övriga...
    2009 (Engelska)Ingår i: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 115, nr 20, s. 4679-87Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND: Trial accrual patterns were examined to determine whether metastatic colorectal cancer (mCRC) patients enrolled in trials are representative of a general cancer population concerning patient characteristics and survival.

    METHODS: A total of 760 mCRC patients referred for their first oncological consideration at 3 hospitals in Scandinavia covering defined populations were registered consecutively during 2003 to 2006. Clinical trial enrollment, patient characteristics, and treatment were recorded prospectively, and the follow-up was complete.

    RESULTS: Palliative chemotherapy was initiated in 61% of the patients. Approximately one-third (36%) of patients receiving chemotherapy were included in a trial. The main reason for nonparticipation was failed eligibility criteria (69%). The median survival after chemotherapy was 15.8 months for all patients, and 18 months after combination chemotherapy. Trial patients had better prognostic characteristics and significantly longer survival than nontrial patients: 21.3 months versus 15.2 months when receiving combination chemotherapy. Poor performance status was the main reason for giving best supportive care only, and the median survival was then only 2.1 months. The median survival for all 760 nonresectable mCRC patients was 10.7 months.

    CONCLUSIONS: mCRC patients enrolled into clinical trials differ in characteristics from patients receiving chemotherapy outside protocol and have better survival, even when given the same treatment. Although trial patients have a median survival close to 2 years, survival is lower for all patients receiving chemotherapy and much lower for all patients diagnosed with mCRC. Studies that better accept the heterogeneity of the population with mCRC are needed.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-113895 (URN)10.1002/cncr.24527 (DOI)000270740900007 ()19562777 (PubMedID)
    Tillgänglig från: 2010-02-04 Skapad: 2010-02-04 Senast uppdaterad: 2017-12-12Bibliografiskt granskad
    3. Lower treatment intensity and poorer survival in metastatic colorectal cancer patients who live alone
    Öppna denna publikation i ny flik eller fönster >>Lower treatment intensity and poorer survival in metastatic colorectal cancer patients who live alone
    Visa övriga...
    2012 (Engelska)Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 107, nr 1, s. 189-194Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND: Socioeconomic status (SES) and social support influences cancer survival. If SES and social support affects cancer treatment has not been thoroughly explored. METHODS: A cohort consisting of all patients who were initially diagnosed with or who developed metastatic colorectal cancer (mCRC, n = 781) in three Scandinavian university hospitals from October 2003 to August 2006 was set up. Clinical and socioeconomic data were registered prospectively. RESULTS: Patients living alone more often had synchronous metastases at presentation and were less often treated with combination chemotherapy than those cohabitating (HR 0.19, 95% CI 0.04-0.85, P = 0.03). Surgical removal of metastases was less common in patients living alone (HR 0.29, 95% CI 0.10-0.86, P = 0.02) but more common among university-educated patients (HR 2.22, 95% CI 1.10-4.49, P = 0.02). Smoking, being married and having children did not influence treatment or survival. Median survival was 7.7 months in patients living alone and 11.7 months in patients living with someone (P < 0.001). Living alone remained a prognostic factor for survival after correction for age and comorbidity. CONCLUSION: Patients living alone received less combination chemotherapy and less secondary surgery. Living alone is a strong independent risk factor for poor survival in mCRC. 

    Nationell ämneskategori
    Cancer och onkologi
    Identifikatorer
    urn:nbn:se:uu:diva-172517 (URN)10.1038/bjc.2012.186 (DOI)000305888400029 ()
    Tillgänglig från: 2012-04-11 Skapad: 2012-04-11 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    4. Equal cancer treatment regardless of education level and family support?: A qualitative study of oncologists’ decision-making
    Öppna denna publikation i ny flik eller fönster >>Equal cancer treatment regardless of education level and family support?: A qualitative study of oncologists’ decision-making
    2012 (Engelska)Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 2, nr 4, s. e001248-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objective: Treatment gradients by socioeconomic status have been observed within cancer care in several countries. The objective of this study was to explore whether patients' educational level and social network influence oncologists' clinical decision-making. Design: Semi-structured interviews on factors considered when deciding on treatment for cancer patients. Interviews were transcribed and analysed using inductive qualitative content analysis. Setting: Oncologists in Swedish university-and non-university hospitals were interviewed in their respective places of work. Participants: Twenty Swedish clinical oncologists selected through maximum-variation sampling. Primary and secondary outcome measures: Elements which influence oncologists' decision-making process were explored with focus on educational level and patients' social support systems. Results: Oncologists consciously used less combination chemotherapy for patients living alone, fearing treatment toxicity. Highly educated patients were considered as well-read, demanding and sometimes difficult to reason with. Patients with higher education, those very keen to have treatment and persuasive relatives were considered as challenges for the oncologist. Having large groups of relatives in a room made doctors feel outnumbered. A desire to please patients and relatives was posed as the main reason for giving in to patients' demands, even when this resulted in treatment with limited efficacy. Conclusions: Oncologists tailor treatment for patients living alone to avoid harmful side-effects. Many find patients' demands difficult to handle and this may result in strong socioeconomic groups being over-treated.

    Nationell ämneskategori
    Cancer och onkologi
    Identifikatorer
    urn:nbn:se:uu:diva-172518 (URN)10.1136/bmjopen-2012-001248 (DOI)000315049300078 ()
    Tillgänglig från: 2012-04-11 Skapad: 2012-04-11 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
  • 296.
    Cavalli-Björkman, Nina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Strang, Peter
    Equal cancer treatment regardless of education level and family support?: A qualitative study of oncologists’ decision-making2012Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 2, nr 4, s. e001248-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Treatment gradients by socioeconomic status have been observed within cancer care in several countries. The objective of this study was to explore whether patients' educational level and social network influence oncologists' clinical decision-making. Design: Semi-structured interviews on factors considered when deciding on treatment for cancer patients. Interviews were transcribed and analysed using inductive qualitative content analysis. Setting: Oncologists in Swedish university-and non-university hospitals were interviewed in their respective places of work. Participants: Twenty Swedish clinical oncologists selected through maximum-variation sampling. Primary and secondary outcome measures: Elements which influence oncologists' decision-making process were explored with focus on educational level and patients' social support systems. Results: Oncologists consciously used less combination chemotherapy for patients living alone, fearing treatment toxicity. Highly educated patients were considered as well-read, demanding and sometimes difficult to reason with. Patients with higher education, those very keen to have treatment and persuasive relatives were considered as challenges for the oncologist. Having large groups of relatives in a room made doctors feel outnumbered. A desire to please patients and relatives was posed as the main reason for giving in to patients' demands, even when this resulted in treatment with limited efficacy. Conclusions: Oncologists tailor treatment for patients living alone to avoid harmful side-effects. Many find patients' demands difficult to handle and this may result in strong socioeconomic groups being over-treated.

  • 297.
    Cavalli-Björkman, Nina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Qvortrup, Camilla
    Sebjørnssen, Sigrunn
    Pfeiffer, Per
    Wentzel-Larsen, Tore
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Sorbye, Halfdan
    Lower treatment intensity and poorer survival in metastatic colorectal cancer patients who live alone2012Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 107, nr 1, s. 189-194Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Socioeconomic status (SES) and social support influences cancer survival. If SES and social support affects cancer treatment has not been thoroughly explored. METHODS: A cohort consisting of all patients who were initially diagnosed with or who developed metastatic colorectal cancer (mCRC, n = 781) in three Scandinavian university hospitals from October 2003 to August 2006 was set up. Clinical and socioeconomic data were registered prospectively. RESULTS: Patients living alone more often had synchronous metastases at presentation and were less often treated with combination chemotherapy than those cohabitating (HR 0.19, 95% CI 0.04-0.85, P = 0.03). Surgical removal of metastases was less common in patients living alone (HR 0.29, 95% CI 0.10-0.86, P = 0.02) but more common among university-educated patients (HR 2.22, 95% CI 1.10-4.49, P = 0.02). Smoking, being married and having children did not influence treatment or survival. Median survival was 7.7 months in patients living alone and 11.7 months in patients living with someone (P < 0.001). Living alone remained a prognostic factor for survival after correction for age and comorbidity. CONCLUSION: Patients living alone received less combination chemotherapy and less secondary surgery. Living alone is a strong independent risk factor for poor survival in mCRC. 

  • 298.
    Cavelier, Lucia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Ameur, Adam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Häggqvist, Susana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Höijer, Ida
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Cahill, Nicola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Olsson-Strömberg, Ulla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Hermanson, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Clonal distribution of BCR-ABL1 mutations and splice isoforms by single-molecule long-read RNA sequencing2015Ingår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 15, artikel-id 45Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The evolution of mutations in the BCR-ABL1 fusion gene transcript renders CML patients resistant to tyrosine kinase inhibitor (TKI) based therapy. Thus screening for BCR-ABL1 mutations is recommended particularly in patients experiencing poor response to treatment. Herein we describe a novel approach for the detection and surveillance of BCR-ABL1 mutations in CML patients. Methods: To detect mutations in the BCR-ABL1 transcript we developed an assay based on the Pacific Biosciences (PacBio) sequencing technology, which allows for single-molecule long-read sequencing of BCR-ABL1 fusion transcript molecules. Samples from six patients with poor response to therapy were analyzed both at diagnosis and follow-up. cDNA was generated from total RNA and a 1,6 kb fragment encompassing the BCR-ABL1 transcript was amplified using long range PCR. To estimate the sensitivity of the assay, a serial dilution experiment was performed. Results: Over 10,000 full-length BCR-ABL1 sequences were obtained for all samples studied. Through the serial dilution analysis, mutations in CML patient samples could be detected down to a level of at least 1%. Notably, the assay was determined to be sufficiently sensitive even in patients harboring a low abundance of BCR-ABL1 levels. The PacBio sequencing successfully identified all mutations seen by standard methods. Importantly, we identified several mutations that escaped detection by the clinical routine analysis. Resistance mutations were found in all but one of the patients. Due to the long reads afforded by PacBio sequencing, compound mutations present in the same molecule were readily distinguished from independent alterations arising in different molecules. Moreover, several transcript isoforms of the BCR-ABL1 transcript were identified in two of the CML patients. Finally, our assay allowed for a quick turn around time allowing samples to be reported upon within 2 days. Conclusions: In summary the PacBio sequencing assay can be applied to detect BCR-ABL1 resistance mutations in both diagnostic and follow-up CML patient samples using a simple protocol applicable to routine diagnosis. The method besides its sensitivity, gives a complete view of the clonal distribution of mutations, which is of importance when making therapy decisions.

  • 299.
    Cazzaniga, Marina E.
    et al.
    ASST Monza, Phase 1 Trials Res Unit, Monza, MB, Italy; ASST Monza, Oncol Unit, Monza, MB, Italy; Milano Bicocca Sch Med, Monza, MB, Italy.
    Ciruelos, E.
    Ctr Integral Oncol Clara Campal HM CIOCC, Unidad Canc Mama, Madrid, Spain.
    Fabi, A.
    Regina Elena Inst Canc Res, Med Oncol, Rome, Italy.
    Garcia-Saenz, J.
    Hosp Clin San Carlos, ISCIII, IdISSC CIBERONC, Dept Med Oncol, Madrid, Spain.
    Lindman, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Mavroudis, D.
    Univ Hosp Heraklion, Dept Med Oncol, Iraklion, Crete, Greece.
    Schem, C.
    Mammazentrum, Hamburg, Germany.
    Steger, G.
    Med Univ Vienna, Dept Internal Med 1, Vienna, Austria.
    Timotheadou, E.
    Aristotle Univ Thessaloniki, Sch Med, Papageorgiou Gen Hosp, Thessaloniki, Greece.
    Zaman, K.
    Univ Hosp CHUV, Dept Oncol, Breast Ctr, Lausanne, Switzerland.
    Torri, V.
    Ist IRCCS Ist Mario Negri, Milan, Italy.
    Metastatic or locally advanced breast cancer patients: towards an expert consensus on nab-paclitaxel treatment in HER2-negative tumoursthe MACBETH project2019Ingår i: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 83, nr 2, s. 301-318Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Despite the large use of nab-paclitaxel as a treatment option in metastatic breast cancer (MBC) across different countries, no definitive data are available in particular clinical situations.

    Areas covered: Efficacy, safety and schedule issues concerning available literature on nab-paclitaxel in advanced breast cancer and in specific subgroups of patients have been discussed and voted during an International Expert Meeting. Ten expert specialists in oncology, with extensive clinical experience on Nab-P and publications in the field of MBC have been identified. Six scientific areas of interest have been covered, generating 13 specific Statements for Nab-P, after literature review. For efficacy issues, a summary of research quality was performed adopting the GRADE algorithm for evidence scoring. The panel members were invited to express their opinion on the statements, in case of disagreement all the controversial opinions and the relative motivations have been made public.

    Expert opinion: Consensus was reached in 30.8% of the Nab-P statements, mainly those regarding safety issues, whereas ones regarding efficacy and schedule still remain controversial areas, requiring further data originated by the literature.

  • 300.
    Cazzaniga, Walter
    et al.
    IRCCS Osped San Raffaele, URI, Unit Urol, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Ventimiglia, Eugenio
    IRCCS Osped San Raffaele, URI, Unit Urol, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Alfano, Massimo
    IRCCS Osped San Raffaele, URI, Unit Urol, Div Expt Oncol, Milan, Italy.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Lissbrant, Ingela Franck
    Univ Goteborg, Sahlgrenska Acad, Dept Oncol, Inst Clin Sci, Gothenburg, Sweden.
    Carlsson, Stefan
    Karolinska Univ Hosp, Div Urol, Stockholm, Sweden;Karolinska Inst, Dept Mol Med & Surg MMK, Stockholm, Sweden.
    Styrke, Johan
    Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
    Montorsi, Francesco
    IRCCS Osped San Raffaele, URI, Unit Urol, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Salonia, Andrea
    IRCCS Osped San Raffaele, URI, Unit Urol, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Mini Review on the Use of Clinical Cancer Registers for Prostate Cancer: The National Prostate Cancer Register (NPCR) of Sweden2019Ingår i: FRONTIERS IN MEDICINE, ISSN 2296-858X, Vol. 6, artikel-id 51Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Given the increasing prevalence of cancer, it is vital to systematically collect data in order to monitor disease trends and quality of cancer care. For this purpose, clinical cancer registries have been developed in some countries. These registers are intended to be used as a basis for quality assurance and quality improvement, but they also constitute a rich resource of real world data for research. The aim of thismini-review was to describe the structure and the organization of the National Prostate Cancer Register (NPCR) with some examples on how data in NPCR have affected prostate cancer care in Sweden.

3456789 251 - 300 av 1999
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf