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  • 201.
    Padhan, Narendra
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab. Rudbeck Lab, S-75185 Uppsala, Sweden..
    Yan, Junhong
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Rudbeck Lab, S-75185 Uppsala, Sweden.;Eindhoven Univ Technol, Inst Complex Mol Syst, Dept Biomed Engn, NL-5600 MB Eindhoven, Netherlands..
    Boge, Annegret
    Protein Simple, 3001 Orchard Pkwy, San Jose, CA 95134 USA..
    Scrivener, Elaine
    Protein Simple, 3001 Orchard Pkwy, San Jose, CA 95134 USA..
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Zieba, Agata
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Rudbeck Lab, S-75185 Uppsala, Sweden..
    Gullberg, Mats
    Olink Biosci, Dag Hammarskjolds Vag 52B, S-75237 Uppsala, Sweden..
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab. Rudbeck Lab, S-75185 Uppsala, Sweden..
    Claesson-Welsh, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab. Rudbeck Lab, S-75185 Uppsala, Sweden..
    Landegren, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab. Rudbeck Lab, S-75185 Uppsala, Sweden..
    Highly sensitive and specific protein detection via combined capillary isoelectric focusing and proximity ligation2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 1490Article in journal (Refereed)
    Abstract [en]

    Detection and quantification of proteins and their post-translational modifications are crucial to decipher functions of complex protein networks in cell biology and medicine. Capillary isoelectric focusing together with antibody-based detection can resolve and identify proteins and their isoforms with modest sample input. However, insufficient sensitivity prevents detection of proteins present at low concentrations and antibody cross-reactivity results in unspecific detection that cannot be distinguished from bona fide protein isoforms. By using DNA-conjugated antibodies enhanced signals can be obtained via rolling circle amplification (RCA). Both sensitivity and specificity can be greatly improved in assays dependent on target recognition by pairs of antibodies using in situ proximity ligation assays (PLA). Here we applied these DNA-assisted RCA techniques in capillary isoelectric focusing to resolve endogenous signaling transducers and isoforms along vascular endothelial growth factor (VEGF) signaling pathways at concentrations too low to be detected in standard assays. We also demonstrate background rejection and enhanced specificity when protein detection depended on binding by pairs of antibodies using in situ PLA, compared to assays where each antibody preparation was used on its own.

  • 202. Pagoldh, Maria
    et al.
    Eriksson, Anders
    Heimtun, Erling
    Kvifors, Eva
    Sternby, Berit
    Blomquist, Lars
    Lapidus, Annika
    Suhr, Ole
    Lange, Stefan
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nordström, Daniel
    Rettrup, Björn
    Effects of a supplementary diet with specially processed cereals in patients with short bowel syndrome2008In: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 20, no 11, p. 1085-93Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Short bowel syndrome patients frequently experience impaired health-related quality of life. This syndrome is also associated with increased costs for the individuals concerned and the community. Intake of specially processed cereals has been demonstrated to decrease intestinal secretion. This study evaluates the effect of a supplementary diet with specially processed cereals compared with nonprocessed cereals. METHODS: This investigation is a randomized double-blind, cross-over multicentre prospective study of 26 intestinal resected out patients, considered as short bowel syndrome patients. The patients were divided into groups A or B, in accordance with the first allocated treatment. Subgroup analyses of the underlying diagnoses and type of surgical procedure were performed. The studied parameters were faecal volume, nocturnal stools, abdominal pain/discomfort, health-related quality of life, peripheral blood tests and anthropometric data. RESULTS: In both groups, intake of nonprocessed cereals significantly decreased the faecal volume. The subgroup analyses of patients with a history of ulcerative colitis (compared with Crohn's disease) and nonileostomy-operated procedure (compared with ileostomi-operated procedure) showed significantly decreased faecal volume during nonprocessed cereals intake. Peripheral blood tests, quality of life and anthropometry were not affected. CONCLUSION: In this study, nonprocessed cereals seemed to be as effective as specially processed cereals in decreasing faecal volume in general and especially in ulcerative colitis patients (mainly operated with nonileostomy techniques). Our results indicate that use of supplementary cereals is safe for this group of patients, but should optimally include evaluation of the underlying diagnosis and the surgical method used.

  • 203. Pathak, S
    et al.
    Nunes, Q M
    Daniels, I R
    Smart, N J
    Poston, G J
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Rectal cancer with synchronous liver metastases: Do we have a clear direction?2015In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 41, no 12, p. 1570-1577Article in journal (Refereed)
    Abstract [en]

    Rectal cancer is a common entity and often presents with synchronous liver metastases. There are discrepancies in management guidelines throughout the world regarding the treatment of advanced rectal cancer, which are further compounded when it presents with synchronous liver metastases. The following article examines the evidence regarding treatment options for patients with synchronous rectal liver metastases and suggests potential treatment algorithms.

  • 204. Pena, Cristina
    et al.
    Virtudes Cespedes, Maria
    Lindh, Maja Bradic
    Kiflemariam, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Mezheyeuski, Artur
    Edqvist, Per-Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Hagglof, Christina
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Bojmar, Linda
    Jirstrom, Karin
    Sandstrom, Per
    Olsson, Eleonor
    Veerla, Srinivas
    Gallardo, Alberto
    Sjöblom, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Chang, Andy C. -M.
    Reddel, Roger R.
    Mangues, Ramon
    Augsten, Martin
    Ostman, Arne
    STC1 Expression By Cancer-Associated Fibroblasts Drives Metastasis of Colorectal Cancer2013In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 74, no 4, p. 1287-1297Article in journal (Refereed)
    Abstract [en]

    Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant of cancer-associated fibroblasts (CAF). Elevated expression of PDGF receptors on stromal CAFs is associated with metastasis and poor prognosis, but mechanism(s) that underlie these connections are not understood. Here, we report the identification of the secreted glycoprotein stanniocalcin-1 (STC1) as a mediator of metastasis by PDGF receptor function in the setting of colorectal cancer. PDGF-stimulated fibroblasts increased migration and invasion of cocultured colorectal cancer cells in an STC1-dependent manner. Analyses of human colorectal cancers revealed significant associations between stromal PDGF receptor and STC1 expression. In an orthotopic mouse model of colorectal cancer, tumors formed in the presence of STC1-deficient fibroblasts displayed reduced intravasation of tumor cells along with fewer and smaller distant metastases formed. Our results reveal a mechanistic basis for understanding the contribution of PDGF-activated CAFs to cancer metastasis.

  • 205. Penninckx, Freddy
    et al.
    Krivokapic, Zoran
    O'Connell, Ronan
    Pfeifer, Johann
    Schiedeck, Thomas
    Tiret, Emmanuel
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Haboubi, Najib
    Post, Stefan
    Kassai, Miklos
    Engel, Alexander
    Pfeifer, Johann
    Martling, Anna
    Letter from the ESCP Executive2011In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 13, no 10, p. 1188-1189Article in journal (Refereed)
  • 206. Pettersson, D.
    et al.
    Cedermark, B.
    Holm, T.
    Radu, Calin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Martling, Anna
    Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer2010In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 97, no 4, p. 580-587Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To address issues regarding the fractionation of radiotherapy (RT) and timing of surgery for rectal cancer, a multicentre trial has randomized patients to preoperative short-course RT with two different intervals to surgery, or long-course RT with delayed surgery. The present interim analysis assessed feasibility, compliance and complications after RT and surgery. METHODS: Some 303 patients were randomized to either short-course RT (5 x 5 Gy) and surgery within 1 week (group 1), short-course RT and surgery after 4-8 weeks (group 2) or long-course RT (25 x 2 Gy) and surgery after 4-8 weeks (group 3). RESULTS: Demographic data were similar between groups and there were few protocol violations (5.0-6 per cent). Eight patients (2.6 per cent) developed radiation-induced acute toxicity. There were no significant differences in postoperative complications between groups (46.6, 40.0 and 32 per cent in groups 1, 2 and 3 respectively; P = 0.164). Patients receiving short-course RT with surgery 11-17 days after the start of RT had the highest complication rate (24 of 37). CONCLUSION: Compliance was acceptable and severe acute toxicity was low, irrespective of fractionation. Short-course RT with immediate surgery had a tendency towards more postoperative complications, but only if surgery was delayed beyond 10 days after the start of RT. Registration number: NCT00904813 (http://www.clinicaltrials.gov).

  • 207. Picelli, Simone
    et al.
    Zajac, Pawel
    Zhou, Xiao-Lei
    Edler, David
    Lenander, Claes
    Dalén, Johan
    Hjern, Fredrik
    Lundqvist, Nils
    Lindforss, Ulrik
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Smedh, Kennet
    Törnqvist, Anders
    Holm, Jörn
    Janson, Martin
    Andersson, Magnus
    Ekelund, Susanne
    Olsson, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lundeberg, Joakim
    Lindblom, Annika
    Common variants in human CRC genes as low-risk alleles2010In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 46, no 6, p. 1041-1048Article in journal (Refereed)
    Abstract [en]

    The genetic susceptibility to colorectal cancer (CRC) has been estimated to be around 35% and yet high-penetrance germline mutations found so far explain less than 5% of all cases. Much of the remaining variations could be due to the co-inheritance of multiple low penetrant variants. The identification of all the susceptibility alleles could have public health relevance in the near future. To test the hypothesis that what are considered polymorphisms in human CRC genes could constitute low-risk alleles, we selected eight common SNPs for a pilot association study in 1785 cases and 1722 controls. One SNP, rs3219489:G>C (MUTYH Q324H) seemed to confer an increased risk of rectal cancer in homozygous status (OR=1.52; CI=1.06-2.17). When the analysis was restricted to our 'super-controls', healthy individuals with no family history for cancer, also rs1799977:A>G (MLH1 I219V) was associated with an increased risk in both colon and rectum patients with an odds ratio of 1.28 (CI=1.02-1.60) and 1.34 (CI=1.05-1.72), respectively (under the dominant model); while 2 SNPs, rs1800932:A>G (MSH6 P92P) and rs459552:T>A (APC D1822V) seemed to confer a protective effect. The latter, in particular showed an odds ratio of 0.76 (CI=0.60-0.97) among colon patients and 0.73 (CI=0.56-0.95) among rectal patients. In conclusion, our study suggests that common variants in human CRC genes could constitute low-risk alleles.

  • 208. Punt, Cornelis J A
    et al.
    Buyse, Marc
    Köhne, Claus-Henning
    Hohenberger, Peter
    Labianca, Roberto
    Schmoll, Hans J
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Sobrero, Alberto
    Douillard, Jean-Yves
    Endpoints in adjuvant treatment trials: a systematic review of the literature in colon cancer and proposed definitions for future trials.2007In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 99, no 13, p. 998-1003Article in journal (Refereed)
    Abstract [en]

    Disease-free survival is increasingly being used as the primary endpoint of most trials testing adjuvant treatments in cancer. Other frequently used endpoints include overall survival, recurrence-free survival, and time to recurrence. These endpoints are often defined differently in different trials in the same type of cancer, leading to a lack of comparability among trials. In this Commentary, we used adjuvant studies in colon cancer as a model to address this issue. In a systematic review of the literature, we identified 52 studies of adjuvant treatment in colon cancer published in 1997–2006 that used eight other endpoints in addition to overall survival. Both the definition of these endpoints and the starting point for measuring time to the events that constituted these endpoints varied widely. A panel of experts on clinical research on colorectal cancer then reached consensus on the definition of each endpoint. Disease-free survival—defined as the time from randomization to any event, irrespective of cause—was considered to be the most informative endpoint for assessing the effect of treatment and therefore the most relevant to clinical practice. The proposed guidelines may add to the quality and cross-comparability of future studies of adjuvant treatments for cancer.

  • 209.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Ackreditering i Kolorektal Kirurgi2007In: Svensk Kirurgi, ISSN 0346-847X, no 6, p. 262-263Article in journal (Refereed)
    Abstract [sv]

    Uppsalabo, Sörmlänning, Europé. Lars Påhlman botaniserar här i att befästa att kunskaper erhållits under en subspecialisering i kolorektalkirurgin genom ackreditering utifrån svenskt och europeiskt perspektiv.

  • 210.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Commentary.2008In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 11, no 4, p. 364-5Article in journal (Refereed)
  • 211.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Fecal Incontinence: Foreword2007In: Fecal Incontinence: Diagnosis and Treatment / [ed] Carlo Ratto, Giovanni B. Doglietto, Ann C. Lowry, Lars Påhlman & Giovanni Romano, Milano: Springer , 2007, p. VII-VIIIChapter in book (Other academic)
  • 212.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Fel att neka patienter botande behandling bara för att den är dyr2010In: Dagens medicin, Vol. 15, p. 19-Article in journal (Refereed)
  • 213.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    How to Evaluate the Quality of Surgery? Suggestions for Critical Reading of Surgical and Pathological Reports2012In: Multidisciplinary Management of Rectal Cancer / [ed] Vincenzo Valentini, H -J Schmoll, Cornelis J H van de Velde, Heidelberg: Springer, 2012, p. 229-232Chapter in book (Other academic)
    Abstract [en]

    Quality in the surgical treatment of rectal cancer can be divided in two main parts. One is the quality of the excised specimen, where data do indicate that a completely excised rectal cancer specimen (total mesorectal excision) is the cornerstone for a successful outcome. This can be evaluated by the pathologist. The other part is the overall care according to guidelines including staging, type of surgery, complications to treatment, use of chemo- and radiotherapy, long-term results, etc., which can be audit in quality registries.

  • 214.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Intressanta data i Rektalcancerregistret2011In: Svensk Kirurgi, ISSN 0346-847X, Vol. 69, no 6, p. 318-320Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Det är väl känt att vissa patienter inte klarar primäringreppet vid kolorektal kirurgi och att reopereration krävs. Hela beslutsprocessen runt en reoperation och den efterkommande vården har man försökt värdera med begreppet failure-to-rescue (FTR) i denna artikel.

  • 215.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Jag anser att alla patienter med kolorektal cancer bör diskuteras i MDT-konferens!2012In: Svensk Kirurgi, ISSN 0346-847X, Vol. 70, no 3, p. 152-153Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Utifrån resursskäl diskuterade några kollegor i föregående nummer av Svensk Kirurgi huruvida samtliga patienter med kolorektal cancer behöver diskuteras på multi­ disciplinär konferens. Solklara fall skulle då istället kunna sättas upp för terapi direkt. Professor Lars Påhlman, Uppsala, replikerar här att det finns flera skäl som talar för att alla verkligen skall diskuteras. 

  • 216.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Koloskopi för alla 60-åringar skulle rädda många liv2008In: Rädda livet: Cancerfondens tidning, ISSN 0284-1037, no 2, p. 22-Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Välskötta nationella register och allmän screening av 60-åringar i Sverige förebygger insjuknandet av cancer i tjock- och ändtarm, och minskar dödligheten väsentligt.

  • 217.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Kommentar till Järhults replik2012In: Svensk Kirurgi, ISSN 0346-847X, Vol. 70, no 4, p. 230-230Article in journal (Other (popular science, discussion, etc.))
  • 218.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Kvalitetsregister för ändtarmscancer2011In: Kanalen: medlemstidningen inom Mag- och tarmförbundet, no 1, p. 4-4Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Rektalcancer (ändtarmscancer) är en vanlig tumörform i Sverige. På grund av hög dödlighet samt dåliga cancerresultat på tidigt 80-tal, startades Svenska Rektalcancerregistret. Avsikten med registret är att studera på vilket sätt kirurgin vid rektalcancer ytterligare kan förbättras för att förbättra situationen för patienterna. Målet är att de kvalitetsparametrar vi identifierar ska ligga som riktlinjer för den fortsatta vården.

  • 219.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Lokalrecidiv vid rektalcancer: vart är vi på väg i Sverige?2011In: Svensk Kirurgi, ISSN 0346-847X, Vol. 69, no 2, p. 66-67Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Svensk vård för rektalcancer ligger i världsklass. Patienterna önskar att vi försvarar vår position. Styrgruppen för kolorektalcancerregistret ser med viss oro en tendens till ökande lokalrecidiv och analyserar tänkbara bakomliggande orsaker.

  • 220.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Management of carcinoma of the rectum2008In: Surgery of the Anus, Rectum and Colon / [ed] Michael R. B. Keighley & Norman S. Williams, London: Saunders , 2008, 3, p. 1115-1262Chapter in book (Other academic)
  • 221.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nytt mått på vårdkvalitet vid kolorektal reoperation prövat2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 23-24, p. 1153-1153Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Det är väl känt att vissa patienter inte klarar primäringreppet vid kolorektal kirurgi och att reopereration krävs. Hela beslutsprocessen runt en reoperation och den efterkommande vården har man försökt värdera med begreppet failure-to-rescue (FTR) i denna artikel.

  • 222.
    Påhlman, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Optimal timing of surgery after preoperative chemoradiotherapy for rectal cancer2009In: Nature clinical practice. Oncology, ISSN 1743-4254, Vol. 6, no 3, p. 128-9Article in journal (Refereed)
    Abstract [en]

    The timing of surgery in rectal cancer treatment after neoadjuvant chemoradiotherapy is debated, mainly because of downsizing and repopulation of tumor cells. The retrospective analysis of prospectively collected data from a series of patients with locally advanced rectal cancer by Lim et al. has tried to evaluate whether timing of surgery after neoadjuvant chemoradiotherapy has any effect on tumor regression, sphincter preservation, local recurrence rate or overall survival. The study included 397 patients who had received chemoradiotherapy and surgery with different time intervals between the use of these modalities. No differences regarding all four parameters were found in patients with a time interval less or greater than 41 days. Some methodological reasons can be discussed, but the only way to answer the question of timing is, of course, to do a randomized trial.

  • 223.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Preoperative short-course radiotherapy in locally advanced rectal cancer: The attitude on how to use radiotherapy in rectal cancer is changing2008In: Onkologie (Basel), ISSN 0378-584X, E-ISSN 1423-0240, Vol. 31, no 4, p. 165-Article in journal (Other (popular science, discussion, etc.))
  • 224.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Radiation injury to colon and rectum2008In: Surgery of the Anus, Rectum and Colon, Edinburgh: Elsevier Saunders , 2008, 3, p. 2149-2168Chapter in book (Other academic)
  • 225.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Rectal cancer2008In:  Coloproctology, Berlin: Springer Verlag , 2008, p. 213-218Chapter in book (Other (popular science, discussion, etc.))
  • 226.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Strålbehandling vid rektalcancer kräver noggrann preoperativ utredning: Mer nytta än risk om rätt patient strålas2007In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 104, no 34, p. 2314-2315Article in journal (Other academic)
    Abstract [sv]

    Strålbehandling reducerar andelen lokalrecidiv till hälften vid behandling av patienter med rektalcancer.

    Behandlingen medför dock viss långtidstoxicitet, vilket skall beaktas.

    God preoperativ utredning krävs därför för att finna de individer som verkligen har behov av strålbehandling.

  • 227.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Surveillance treatment of recurrence in colorectal cancer2008In: Surgery of the Anus, Rectum and Colon / [ed] Michael R.B. Keighley, Norman S. Williams, Edinburgh: Elsevier Saunders , 2008, 3, p. 1263-1300Chapter in book (Other academic)
  • 228.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Suturteknikkurs KMC i Linköping2007In: Svensk Kirurgi, ISSN 0346-847x, Vol. 65, no 6, p. 255-Article, book review (Other (popular science, discussion, etc.))
  • 229.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Svenska rectalregistret2010In: Svensk Kirurgi, ISSN 0346-847X, Vol. 68, p. 240-242Article in journal (Refereed)
  • 230.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Svenska Rektalcancerregistret2010In: Svensk Kirurgi, ISSN 0346-847X, Vol. 68, no 5, p. 240-242Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    En remarkabel förbättring av svensk rektalcancervård har skett de senaste 20 åren tack vare en rad faktorer. En av dessa har varit ett nationellt heltäckande register. Det är väl förankrat ute på klinikerna och helt transparent för professionen och allmänheten med öppna kvalitetsjämförelser årligen. Något som till syvende och sist gagnar den enskilde patienten.

  • 231.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Tarmcancer: en tidig upptäckt ökar chansen för bot2007In: Apoteket: Tidning för apotekens kunder, ISSN 0349-2516, no 4, p. 24-27Article in journal (Other (popular science, discussion, etc.))
  • 232.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Textbook of Clinical Trials. 2nd Edn: D. Machin, S. Day and S. Green (eds)2007In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 94, no 11, p. 1441-1441Article in journal (Other academic)
  • 233.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    What Is the Appropriate Timetable for Tailored Follow-up?2012In: Multidisciplinary Management of Rectal Cancer / [ed] Vincenzo Valentini, Hans-Joachim Schmoll, Cornelis J H van de Velde, Heidelberg: Springer, 2012, p. 351-354Chapter in book (Other academic)
    Abstract [en]

    Patients with colorectal cancer at risk for developing metastases or in the long run metachronous adenomas or cancers in the bowel should be offered a follow-up programme. In such a programme, consideration has to be taken regarding patients’ co-morbidity, stage of disease and organs to check. For metastatic spread, only those with stage II and III disease, as well as those having been curatively treated for metastases, should be included, and the organs of interest are the liver and lungs. Regarding surveillance for new malignancies in the bowel, all patients irrespective of stage, who are free of disease at 5 years, should be included. The aim of the whole surveillance programme is to find recurrences or a new primary which can be treated radically.

  • 234.
    Påhlman, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Bujko, K.
    Rutkowski, A.
    Michalski, W.
    Altering the therapeutic paradigm towards a distal bowel margin of < 1 cm in patients with low-lying rectal cancer: a systematic review and commentary2013In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 15, no 4, p. E166-E174Article, review/survey (Refereed)
    Abstract [en]

    Aim The 1-cm rule of distal bowel clearance in patients with low-lying rectal cancer undergoing anterior resection is based mainly on pathological data showing distal intramural spread. Because clinical data are contradictory, a review that includes only cancers located 5 or 6cm from the anal verge was carried out. Method A systematic review of the literature identified seven studies that presented results in relation to a margin of 1cm (n=293) vs >1cm (n=315). In six studies, pre- or postoperative radiotherapy was implemented, and in one study patients were treated with surgery alone. Three studies, all implementing radiotherapy, reported results related to a margin of 5mm (n=51) vs >5mm (n=125). Results In none of the studies were the differences in local recurrence rate between the small and large margin groups statistically significant. The pooled analysis of six studies, in which patients received perioperative radiotherapy, showed a 1.2% [95% confidence interval (Cl) 4.57.0%] higher local recurrence rate in the 1cm margin group compared with the >1cm margin group (P=0.6). The corresponding figures for the 5mm cut-off point were 0.5% (95% CI 7.68.7%, P=0.9). The 5-year local recurrence rate in the only study in which radiotherapy had not been used was 8.6% higher in the 1cm margin group compared with the >1cm margin group (P=0.09). Conclusion Clinical evidence does not support the 1-cm rule in patients with low-lying rectal cancer undergoing pre- or postoperative radiotherapy.

  • 235.
    Påhlman, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Role of radiotherapy2008In: International Handbook of Colorectal Cancer / [ed] Jim Cassidy, Euromed Commincations Ltd , 2008, p. 57-70Chapter in book (Other academic)
  • 236.
    Påhlman, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Role of radiotherapy2008In: International Handbook of colorectal cancer / [ed] Jim Cassidy, Euromed Communications Ltd , 2008, p. 57-70Chapter in book (Other (popular science, discussion, etc.))
  • 237.
    Påhlman, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Surgery for rectal prolapse: Functional outcome from the abdominal approach - an overview2008In: Rectal Prolapse: Diagnoses and Clinical management, Milano: Springer , 2008, p. 157-168Chapter in book (Other academic)
  • 238.
    Påhlman, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Krivocapic, Z.
    Surgery for rectal cancer (conventional open surgery)2010In: European Surgery, ISSN 1682-8631, Vol. 42, no 6, p. 267-275Article in journal (Refereed)
    Abstract [en]

    Background Discrepancy exists how to surgically approach rectal cancer (open or minimally invasive) and how to implement neoadjuvant oncological concepts into the treatment algorithm Methods Analysis of the literature regarding the surgical treatment of rectal cancer Results Oncological criteria (resection margin and lymphnode harvest) are equally met by the laparoscopic and open approach, when conducted in experienced centers Due to the pelvic anatomy, the open approach seems to be advantageous for low rectal cancers, when compared to laparocopy Total mesorectal excision should be reserved for low rectal cancers, tumors of the mid and proximal portion of the rectum should be treated by subtotal mesorectal excision Conclusions Laparoscopic rectal surgery can re place the open approach in the majority of the cases Respective expertise is required to reproduce the excellent results of high volume centers

  • 239.
    Påhlman, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Larsson, Jörgen
    Haglund, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Nyström, P-O.
    Lundell, Lars
    Kirurgveckan - huggen i sten eller ett ständigt rörligt mål?2010In: Svensk kirurgi, ISSN 0346-847X, Vol. 68, no 2, p. 76-78Article in journal (Refereed)
  • 240.
    Påhlman, Lars
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Matzel, Klaus
    Division of Coloproctology (UEMS) 20082008In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 10, no 7, p. 727-8Article in journal (Refereed)
  • 241.
    Påhlman, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Matzel, Klaus
    ESCP Report: Division of Coloproctology (UEMS) (2007)2007In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 9, no 7, p. 663-664Article in journal (Refereed)
  • 242.
    Påhlman, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Syk, Ingvar
    Hur ska vi klara av kravet på MDT-konferens för alla?2011In: Svensk Kirurgi, ISSN 0346-847X, Vol. 69, no 4, p. 212-213Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Modern medicinsk kunskap är idag så omfattande och diversifierad att en enskild läkare i många sammanhang inte kan ta ett lika klokt medicinskt beslut som en grupp av kollegor. Terapikonferenser blir därför allt viktigare för de flesta maligna tillstånd men också för vissa benigna åkommor. Styrgruppen för kolorektala cancerregistret vill här understryka vikten av MDT-konferenser.

  • 243.
    Påhlman, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Torkzad, Michael R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Rectal cancer staging: is there an optimal method?2011In: Future Oncology, ISSN 1479-6694, Vol. 7, no 1, p. 93-100Article, review/survey (Refereed)
    Abstract [en]

    The staging process in a newly diagnosed rectal cancer is divided into three parts. One essential part is the local staging, in which both endorectal ultrasound and MRI are used to disclose the size of the tumor and its correlation to the perirectal fascia, and to identify lymph node deposits and vascular invasion. This local staging process will guide clinicians to decide upon not only the type of surgery (local excision or radical surgery) but also whether or not some type of neoadjuvant treatment, such as radiotherapy and/or chemotherapy, is indicated. The second part is to evaluate whether or not the tumor has already metastasized at diagnosis. The most important organs to evaluate are the liver and lungs, and imaging techniques such as ultrasound. CT-scan, or sometimes PET-CT, and MRI can be used. The third important part is to investigate the rest of the large bowel for synchronous adenomas or cancers. This will preferably be done with colonoscopy or CT-colonography and sometimes barium enema. This article discusses the imaging techniques used for local staging and distant metastases.

  • 244.
    Påhlsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Management of carcinoma of the colon2008In: Surgery of the Anus, Rectum and Colon / [ed] Michael R. B. Keighley & Norman S. Williams, London: Saunders , 2008, 3, p. 1047-1114Chapter in book (Other academic)
  • 245.
    Rada-Iglesias, Alvaro
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Enroth, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    Andersson, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Komorowski, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    Wadelius, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Histone H3 lysine 27 trimethylation in adult differentiated colon associated to cancer DNA hypermethylation2009In: Epigenetics, ISSN 1559-2294, Vol. 4, no 2, p. 107-113Article in journal (Refereed)
    Abstract [en]

    DNA hypermethylation of gene promoters is a common epigenetic alteration occurring in cancer cells. However, little is known about the mechanisms instructing these cancer-specific DNA hypermethylation events. Recent reports have suggested that genes bound by polycomb/Histone H3 lysine 27 trimethylation (H3K27me3) in embryonic stem (ES) cells are frequent targets for cancer-specific DNA hypermethylation. This polycomb-premarking is assumed to be restrained to ES cells, even though almost no polycomb/H3K27me3 binding profiles are available for differentiated tissues. We generated H3K27me3 profiles in human normal colon and they significantly overlapped with those of ES cells and genes hypermethylated in colorectal cancer (CRC). Moreover, colon H3K27me3 was more restricted to genes hypermethylated in CRC, while ES H3K27me3 was also common in genes hypermethylated in other tumors. Therefore, the suggested polycomb pre-marking of genes for cancer DNA hypermethylation is not necessarily limited to ES or early precursor cells but can occur later in differentiated tissues.

  • 246.
    Radu, Calin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Berglund, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Short-course preoperative radiotherapy with delayed surgery in rectal cancer: a retrospective study2008In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 87, no 3, p. 343-9Article in journal (Refereed)
    Abstract [en]

    PURPOSE: In the most advanced, non-resectable primary rectal cancers, conventional long-course radiotherapy (RT) (1.8-2Gyx25-28), frequently combined with chemotherapy, has been used since tumour regression is needed in order to allow a radical (R0) resection. In Uppsala, short-course 5x5Gy with planned delayed surgery has been used in patients with contraindications to long-course RT (+/-chemotherapy). The aim is to describe our experience of using this approach in patients not eligible for standard treatment. PATIENTS AND METHODS: During 2002 and 2005, 46 patients with non-resectable rectal cancer (+/-synchronous distant metastases) were treated with 5x5Gy and delayed surgery if possible. The clinical records were retrospectively evaluated. The first group (A) had no metastases (T4NXM0), whereas the other two groups (B+C) had metastases (T4NXM1). In group (B), the patients had predominantly loco-regional disease and were not candidates for combination chemotherapy (high age, co-morbidities), and in group (C) up-front combination chemotherapy was given, with the intention to have surgery of both the primary and the secondaries if sufficient regression at both sites were seen. RESULTS: The patients in the first two groups (A+B) were old (median 79 and 76 years, respectively), and had several co-morbidities. In group (C), median age was 63 years. The 5x5Gy RT was well tolerated by most patients, but grade IV diarrhoea was recorded in three elderly patients. One patient in the group (C) died from neutropenic fever. Many patients were reported to have less local symptoms after the treatment given. Delayed surgery was performed in all but nine patients. Radical surgery (R0+R1) was performed in 22 (92%) (group A), 4 (44%) (group B), and 6 (46%) (group C) patients, respectively. A pCR was seen in four patients (two in group A and two in group C). No postoperative deaths occurred. CONCLUSIONS: Considering the very high age and presence of co-morbidity, the 5x5Gy schedule is well tolerated. Further, considering the very advanced local stage, the schedule has considerable anti-tumour activity and can result in radical surgery in a high proportion of patients.

  • 247.
    Rasmussen, Ib Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Dahlstrand, Ursula
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Sandblom, Gabriel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Eriksson, Lars-Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Fractures of self-expanding metallic stents in periampullary malignant biliary obstruction2009In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 50, no 7, p. 730-7Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Self-expanding metallic stents are widely used for relieving biliary duct obstruction in patients with unresectable periampullary malignancies. However, only a few studies have assessed the occurrence of fractures in these stents. PURPOSE: To determine the prevalence and significance of stent fracture after placement of self-expanding metallic stents for periampullary malignant biliary obstruction. MATERIAL AND METHODS: Over a 5-year period, 48 patients underwent placement of self-expanding metallic stents for periampullary malignant biliary obstructions. Stents were introduced 2-6 weeks after a percutaneous transhepatic biliary decompression. The medical records and relevant images were reviewed for stent patency, stent fracture, type of stent, and stent-related complications. RESULTS: Stent fracture was detected in four of the 48 patients (8%): in one patient at 1 month and in three patients between 10 and 21 months after stenting. All four fractures involved one type of nitinol stent used in 38 patients. In one of the patients, fracture was complicated by life-threatening gastrointestinal bleeding. The mean survival time for all patients was 251 days (standard deviation [SD]+/-275 days) and the mean overall patency time for all stents was 187 days (SD+/-205 days). CONCLUSION: Stent fracture occurs after placement of self-expanding nitinol stents for periampullary malignant biliary obstruction. The low reported incidence of this complication may be due to a lack of awareness of and difficulty in detecting stent fracture. Fracture should be considered as a possible contributing factor in recurrent biliary obstruction after self-expanding metallic stent insertion.

  • 248.
    Rasmussen, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Kultima, Hanna Göransson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Isaksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Allele-specific copy number analysis of tumor samples with aneuploidy and tumor heterogeneity2011In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 12, no 10, p. R108-Article in journal (Refereed)
    Abstract [en]

    We describe a bioinformatic tool, Tumor Aberration Prediction Suite (TAPS), for the identification of allele-specific copy numbers in tumor samples using data from Affymetrix SNP arrays. It includes detailed visualization of genomic segment characteristics and iterative pattern recognition for copy number identification, and does not require patient-matched normal samples. TAPS can be used to identify chromosomal aberrations with high sensitivity even when the proportion of tumor cells is as low as 30%. Analysis of cancer samples indicates that TAPS is well suited to investigate samples with aneuploidy and tumor heterogeneity, which is commonly found in many types of solid tumors.

  • 249.
    Rolny, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Cancer and Vascular Biology.
    Mazzone, Massimiliano
    Tugues, Sònia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Cancer and Vascular Biology.
    Laoui, Damya
    Johansson, Irja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Coulon, Cathy
    Squadrito, Mario Leonardo
    Segura, Inmaculada
    Li, Xiujuan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Cancer and Vascular Biology.
    Knevels, Ellen
    Costa, Sandra
    Vinckier, Stefan
    Dresselaer, Tom
    Åkerud, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    De Mol, Maria
    Salomäki, Henriikka
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Phillipson, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Wyns, Sabine
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Buysschaert, Ian
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Himmelreich, Uwe
    Van Ginderachter, Jo A.
    De Palma, Michele
    Dewerchin, Mieke
    Claesson-Welsh, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Cancer and Vascular Biology.
    Carmeliet, Peter
    HRG Inhibits Tumor Growth and Metastasis by Inducing Macrophage Polarization and Vessel Normalization through Downregulation of PIGF2011In: Cancer Cell, ISSN 1535-6108, E-ISSN 1878-3686, Vol. 19, no 1, p. 31-44Article in journal (Refereed)
    Abstract [en]

    Polarization of tumor-associated macrophages (TAMs) to a proangiogenic/immune-suppressive (M2-like) phenotype and abnormal, hypoperfused vessels are hallmarks of malignancy, but their molecular basis and interrelationship remains enigmatic. We report that the host-produced histidine-rich glycoprotein (HRG) inhibits tumor growth and metastasis, while improving chemotherapy. By skewing TAM polarization away from the M2- to a tumor-inhibiting M1-like phenotype, HRG promotes antitumor immune responses and vessel normalization, effects known to decrease tumor growth and metastasis and to enhance chemotherapy. Skewing of TAM polarization by HAG relies substantially on downregulation of placental growth factor (PIGF). Besides unveiling an important role for TAM polarization in tumor vessel abnormalization, and its regulation by HRG/PIGF, these findings offer therapeutic opportunities for anticancer and antiangiogenic treatment.

  • 250.
    Rönnblom, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Holmström, Tommy
    Dept Internal Med, Mariehamn, Aland, Finland..
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Tanghöj, Hans
    Malar Hosp, Dept Internal Med, Eskilstuna, Sweden..
    Thörn, Mari
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Sjöberg, Daniel
    Falun Cent Hosp, Dept Internal Med, Falun, Sweden..
    Clinical course of Crohn's disease during the first 5 years. Results from a population-based cohort in Sweden (ICURE) diagnosed 2005-20092017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 1, p. 81-86Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of the study was to describe the medical treatment, change in phenotype, need for surgery and IBD-associated mortality during the first 5 years after diagnosis. Material and Methods: Patients diagnosed with Crohn's disease including all age groups in the Uppsala healthcare region in the middle of Sweden 2005-2009 were included in the study. Medical notes were scrutinised and patients contacted. Out of 269 patients, 260 (96.3%) could be followed for 5 full years or until death. Results: The following drugs were used: 5-ASA 66.7%, systemic steroids 76.4%, antimetabolites 56.7% and anti-TNF 20.3%. Described with the Montreal classification, the proportion with inflammatory behaviour decreased from 78.1% to 74.0% from diagnosis to end of the observation, patients with stricturing behaviour increased from 13.0% to 15.4% and patients with penetrating behaviour increased from 8.9% to 10.6%. After the first year, 12.4% had been treated with intestinal resection or colectomy, a figure that increased to 14.8 after 5 years. Two patients suffered an IBD-related death. Conclusions: Compared to similar patient cohorts, the present study demonstrates that although the course of Crohn's disease seems difficult to change during the first year after diagnosis, the following years up to 5 years shows a more benign course than has usually been described earlier.

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