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  • 1.
    Eldh, Maria
    et al.
    1.Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg.
    Olofsson Bagge, Roger
    1.Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital.
    Lässer, Cecilia
    1.Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg.
    Svanvik, Joar
    Sahlgrenska universitetssjukhuset, Göteborg.
    Sjöstrand, Margareta
    1.Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg.
    Mattsson, Jan
    1.Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital.
    Lindnér, Per
    1.Transplant Institute, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital.
    Choi, Dong-Sic
    1.Division of Molecular and Life Sciences, Department of Life Science, Pohang University of Science and Technology (POSTECH).
    Gho, Yong Song
    1.Division of Molecular and Life Sciences, Department of Life Science, Pohang University of Science and Technology (POSTECH).
    Lötvall, Jan
    1.Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg.
    MicroRNA in exosomes isolated directly from the liver circulation in patients with metastatic uveal melanoma2014Inngår i: BMC Cancer, ISSN 1471-2407, Vol. 14, nr 962, s. 1-10Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Uveal melanoma is a tumour arising from melanocytes of the eye, and 30 per cent of these patients develop liver metastases. Exosomes are small RNA containing nano-vesicles released by most cells, including malignant melanoma cells. This clinical translational study included patients undergoing isolated hepatic perfusion (IHP) for metastatic uveal melanoma, from whom exosomes were isolated directly from liver perfusates. The objective was to determine whether exosomes are present in the liver circulation, and to ascertain whether these may originate from melanoma cells.

    METHODS:

    Exosomes were isolated from the liver perfusate of twelve patients with liver metastases from uveal melanoma undergoing IHP. Exosomes were visualised by electron microscopy, and characterised by flow cytometry, Western blot and real-time PCR. Furthermore, the concentration of peripheral blood exosomes were measured and compared to healthy controls.

    RESULTS:

    The liver perfusate contained Melan-A positive and RNA containing exosomes, with similar miRNA profiles among patients, but dissimilar miRNA compared to exosomes isolated from tumor cell cultures. Patients with metastatic uveal melanoma had a higher concentration of exosomes in their peripheral venous blood compared to healthy controls.

    CONCLUSIONS:

    Melanoma exosomes are released into the liver circulation in metastatic uveal melanoma, and is associated with higher concentrations of exosomes in the systemic circulation. The exosomes isolated directly from liver circulation contain miRNA clusters that are different from exosomes from other cellular sources.

  • 2.
    Escobar Kvitting, John-Peder
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk fysiologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Sandström, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Thorelius, Lars
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Medicinsk radiologi.
    Kullman, Eric
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Borch, Kurt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Radiofrequency ablation of a liver metastasis complicated by extensive liver necrosis and sepsis caused by gas gangrene2006Inngår i: Surgery, ISSN 0039-6060, E-ISSN 1532-7361, Vol. 139, nr 1, s. 123-125Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    [No abstract available]

  • 3.
    Felldin, M.
    et al.
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Ekberg, J.
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Polanska‐Tamborek, D.
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Hansson, U.
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Sender, M.
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Rizell, M.
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Svanvik, Joar
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Mölne, J.
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Donor monoclonal gammopathy may cause lymphoproliferative disorders in solid organ transplant recipients2016Inngår i: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, American Journal of transplantation, Vol. 16, nr 9, s. 2676-2683Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Prior research on donor monoclonal gammopathy of undetermined significance (MGUS) has been inadequate regarding the risk for lymphoproliferative disease in solid organ transplantation recipients. Seven organ recipients from two different donors developed lymphoproliferative disease. The origin of the malignancy was determined by use of microsatellite analysis, and the plasma of the two donors was analyzed with the use of electrophoresis. The clinical courses of the seven recipients were followed for 36–60 months. One donor transmitted lymphoplasmacytic lymphoma to two kidney recipients and MGUS to a liver recipient, all IgMκ. A second donor caused IgGλ myeloma in two kidney and one liver recipient, and IgGλ gammopathy in a heart recipient. Transplant nephrectomy was performed in three kidney recipients and remission was achieved. The fourth kidney recipient has kept the graft and the disease has progressed. The liver recipient died from myeloma. There were no clinical signs of lymphoproliferative disease in the donors, but retrospective serum analyses showed M‐components, IgMκ (37 g/L) and IgGλ (8 g/L). Donors with MGUS may cause donor‐transmitted malignancies via passenger lymphocytes/plasma cells in solid organ recipients. The results call for a large register study of the incidence of donor MGUS and lymphoproliferative disease in their recipients.

  • 4. Ihse, Ingemar
    et al.
    Anderson, Roland
    Blind, Jonas
    Borgström, Anders
    Gasslander, Thomas
    Haglund, Ulf
    Henriksson, Bengt Åke
    Hyltander, Anders
    Larsson, Jörgen
    Lundstedt, Christer
    Permert, Johan
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Riktlinjer för handläggning av patienter med akut pankreatit.2000Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 97, s. 2216-2223Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 5.
    Ihse, Ingemar
    et al.
    Depts. of Surgery and Pharmacology, University of Lund, Lund.
    Permert, Johan
    Institutionen för klinisk vetenskap, intervention och teknik (CLINTEC), Enheten för kirurgi, Karolinska Universitetssjukhuset, Stockholm.
    Andersson, Roland
    Lund University.
    Borgström, Anders
    Department of Surgery, Malmö University Hospital, University of Lund, Malmö.
    Dawiskiba, Sigmund
    Department of Pathology and Cytology, University Hospital, Lund.
    Enander, Lars Krister
    Glimelius, Bengt
    Department of Oncology, Radiology, and Clinical Immunology, Uppsala University, Uppsala.
    Hafström, Larsolof
    Department of Surgery, Umeå University Hospital, Umeå.
    Haglund, Ulf
    Department of Surgical Sciences, Section Surgery, Uppsala University, Uppsala.
    Larsson, Jörgen
    Linköpings universitet, Medicinska fakulteten.
    Lindell, Gert
    Department of Surgery, Lund University Hospital, Lund.
    Olmarker, Anne
    Department of Radiology, Sahlgrenska University Hospital, Göteborg.
    von Rosen, Anette
    Department of Surgery, Karolinska University Hospital, Stockholm.
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Svensson, Jan-Olof
    Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital-Huddinge, Karolinska Institutet, Stockholm.
    Thune, Anders
    Department of Surgery, Sahlgrenska University Hospital, Gothenburg.
    Tranberg, Karl Göran
    Department of Surgery, Lund University Hospital.
    Riktlinjer för handläggning av patienter med pankreascancer [Guidelines for management of patients with pancreatic cancer]2002Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 99, nr 15, s. 1676-1685Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [sv]

    Transabdominellt ultraljud är förstahandsundersökning vid misstänkt pankreascancer, följt av spiral-DT eller MR för mer definitiv diagnos. Tumörmarkörer har ingen plats i rutindiagnostiken. Spiral-DT är basen i resektabilitetsbedömningen. Resektion av tumören är en förutsättning för bot. Ett samband har påvisats mellan antalet resektioner som görs vid ett sjukhus årligen och postoperativ mortalitet. Långtidsöverlevnaden efter resektion är oförändrat kort medan postoperativ mortalitet minskat dramatiskt vid enheter som rapporterat sina resultat. Adjuvant behandling efter resektion bör endast ges inom ramen för kliniska studier. Det palliativa omhändertagandet har förbättrats främst genom utveckling inom endoskopi, interventionell radiologi, smärt- och nutritionsbehandling. Palliativ cytostatikabehandling bör endast ges selektivt utanför kliniska studier. Radioterapi har ingen dokumenterad effekt på överlevnaden vid icke-resektabel pankreascancer. Internationellt rekommenderas speciella behandlingsteam för pankreascancer med tillräckliga upptagningsområden (2–4 miljoner invånare).

  • 6.
    Kuremu, RT
    et al.
    Department of Surgery, Faculty of Health Sciences, Moi University, Eldoret, Kenya.
    Khwa-Otsyula, BO
    Duke University, Durham, UK.
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Bwombengi, OSG
    Eldoret, Rift Valley, Kenya.
    Lelei, LK
    St Luke’s Orthopaedic & Trauma Hospital, Eldoret, Kenya.
    Mathews, D
    University of Maine, Orono, ME .
    Hydatid disease of the spine: Case report2002Inngår i: East African Medical Journal, ISSN 0012-835X, Vol. 79, nr 3, s. 165-166Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A rare case of spinal hydatid disease presenting with paraparesis and sensory loss is reported. The patient was treated with albendazole resulting in significant improvement within eight weeks. Investigations and treatment modalities are discussed.

  • 7.
    Källström, Reidar
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Urologiska kliniken i Östergötland.
    Hjertberg, Hans
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Urologiska kliniken i Östergötland.
    Kjölhede, Henrik
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Use of a virtual reality, real-time, simulation model for the training of urologists in transurethral resection of the prostate2005Inngår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 39, nr 4, s. 313-320Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective. There is a growing need to develop surgical skills outside the operating theatre. In this study we describe the development of a virtual reality training system for practising transurethral resection of the prostate (TURP). Material and methods. A face validity study was performed using a questionnaire sent to 28 experienced urologists to find out the ideal characteristics of a simulated TURP. Based on the comments a simulator was constructed and a content validity study was then performed in which nine experienced urologists tested the simulator and answered a second questionnaire. After corrections to the simulator, a basic construct validity test was performed. Results. We have developed a computer-based simulator based on the requirements listed by 17 urologists. It consists of a modified resectoscope connected to a haptic device and supported by a frame. The software provides a virtual view of the prostatic lumen and resectoscope tip, a haptic rendering that generates force feedback and a simulation module that computes the information from the haptic device, resectoscope fluid tap and handle and the foot pedals. The software also simulates bleeding, absorption of irrigation fluid and pressure gradients. Variables are measured and presented in a result file after each "operation". Nine experienced urologists performed a content validity study and changes were made accordingly. A basic construct validity test performed by seven inexperienced students showed a significant improvement in performance after they each performed six simulated procedures. Conclusion. We have developed a simulator that may be used to practise TURP and which meets most of the demands raised in a face validity study. A basic construct validity test showed improved performance after repeated practice in the simulated environment.

  • 8.
    Källström, Reidar
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Urologiska kliniken i Östergötland.
    Hjertberg, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Urologiska kliniken i Östergötland.
    Svanvik, Joar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Construct validity of a full procedure, virtual reality, real-time, simulation model for training in transurethral resection of the prostate.2010Inngår i: Journal of endourology / Endourological Society, ISSN 1557-900X, Vol. 24, nr 1, s. 109-15Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: To examine the content and construct validity of a full procedure transurethral prostate resection simulation model (PelvicVision). MATERIALS AND METHODS: The full procedure simulator consisted of a modified resectoscope connected to a robotic arm with haptic feedback, foot pedals, and a standard desktop computer. The simulation calculated the flow of irrigation fluid, the amount of bleeding, the corresponding blood fog, the resectoscope movements, resection volumes, use of current, and blood loss. Eleven medical students and nine clinically experienced urologists filled in questionnaires regarding previous experiences, performance evaluation, and their opinion of the usefulness of the simulator after performing six (students) and three (urologists) full procedures with different levels of difficulty. Their performance was evaluated using a checklist. RESULTS: The urologists finished the procedures in half the time as the students with the same resection volume and blood loss but with fewer serious perforations of the prostatic capsule and/or sphincter area and less irrigation fluid uptake. The resectoscope tip movement was longer and the irrigation fluid uptake per resected volume was about 5 times higher for the students. The students showed a positive learning curve in most variables. CONCLUSION: There is proof of construct validity and good content validation for this full procedure simulator for training in transurethral resection of the prostate. The simulator could be used in the early training of urology residents without risk of negative outcome.

  • 9.
    Källström, Reidar
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Urologiska kliniken i Östergötland.
    Hjertberg, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Urologiska kliniken i Östergötland.
    Svanvik, Joar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Impact of Virtual Reality-Simulated Training on Urology Residents Performance of Transurethral Resection of the Prostate2010Inngår i: Journal of endourology, ISSN 0892-7790, E-ISSN 1557-900X, Vol. 24, nr 9, s. 1521-5128Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: There are today a number of VR-simulators for practicing the TURP procedure, but few data on the effect of training on surgical performance.

    Objective: To test if practicing the TURP procedure in a VR-simulator increases the skills and dexterity of urology residents when performing the procedure on patients. Design, setting and participants Twenty-four urology residents attended a five-day course on diagnosis and treatment of benign prostatic enlargement. Each of the residents did three video-recorded TURP procedures on patients.

    Intervention: Between two of the procedures the residents underwent criterion-based practice in a TURP simulator (PelvicVision).

    Measurements: The TURP procedure was peroperatively evaluated using objective structured assessment of technical skills (OSATS). The video-recordings of the procedures were analyzed on a minute to minute basis regarding the main action during that minute, if that action was successful, and errors.

    Results and Limitations: The participating residents rated patient safety as high, they believed they learned most from the real operations, and they gained knowledge about both the procedure and the instrumentation used. The mean practice time in the simulator was 198 minutes before reaching the criterion level. Comparison of the first and last TURP procedures showed an increase in autonomous operation time and in successful actions and a decrease in hemostasis time without increased blood loss. The proportion of residents believed able to perform a simple TURP procedure increased from 10% to about 75%. OSATSscores and self-evaluations were significantly improved. The scores increased significantly more with than without simulator practice. The patient follow-up showed no increased risks or poorer results regarding micturition.

    Conclusions: Practice in a simulator based environment improves the skills and dexterity of urology residents when performing the procedure on patients, without increased risks or poorer results for the patients.

  • 10.
    Källström, Reidar
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Urologiska kliniken i Östergötland.
    Rousseau, Andreas
    Linköpings universitet, Institutionen för medicin och hälsa, Anestesiologi med intensivvård. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Bengtsson, Andreas
    Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Hjertberg, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Urologiska kliniken i Östergötland.
    Svanvik, Joar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Simulator performance, psychometrics and personality testing guiding the choice of clinical disciplineManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The complexity of surgical training has increased and surgery put high demands on personal abilities that cannot be met by all even after training. Selection of personnel is critical to many professions, including surgery, but the selection procedure of surgical apprenticeship is not well developed. It would be of value to get an early assessment of important personal features like the ability to learn complex procedures. Further, individuals learn in different ways and the personality may influence this ability. Other important aspects are visuospatial abilities, working memory and executive functioning. These variables are measured in the present study by: learning curves in a TURP VR-simulator, scores from the personality test TCI-R, Rey complex figure and recognition trial, Tower of London (dx) and tests from WAISIII.

    Twenty-four residents in urology performed three real TUR-P procedures and their performances were analyzed with OSATS and video-recordings. The learning curves from the OR were compared with the results from the simulation practice, personality tests and psychometrics using multiple linear regression. The findings from personality and psychometric data were also compared with the general population to see if there are any indications of a “surgical personality”. The urology residents in this sample have a welldeveloped character (effective, mature, reliable, goal-oriented, empathetic, tolerant, supportive, cooperative) and with high reward dependence (tender-hearted, dedicated, sociable) together with better executive planning abilities and better verbal working memory than normal.

    The connections between the operation learning curves and the variables above indicate that a better learning score is associated with a good learning score in a simulated environment, goal-directedness, a high level of impulse control, anticipation of harmful events and responsibility, a balanced attachment style and a good visual spatial memory.

  • 11. Monstein, H-J
    et al.
    Jonsson, Y
    Zdolsek, Johann
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Hand och plastikkirurgi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Hand- och plastikkirurgiska kliniken US.
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Identification of Helicobacter pylori DNA in human cholesterol gallstones2002Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 37, nr 1, s. 112-119Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The gallbladder mucosa secretes hydrogen ions and is covered by mucus. The environmental conditions for bacterial colonization are similar to those in the stomach. Gallbladder stones often contain DNA from enteric bacteria, but no compelling evidence demonstrates that Helicobacter spp. have been present. The aim of this study was to establish bacterial DNA profiles in cholesterol gallstones with special reference to Helicobacter pylori. Methods: Cholesterol gallstones from 20 patients were subjected to polymerase chain reaction, bacterial profiling by temporal temperature gradient gel electrophoresis, automated DNA sequencing, and Southern blot analysis using a Helicobacter sp. specific primer. A nested ureI-PCR assay was used to discriminate between gastric and non-gastric H. pylori. Results: TTGE, partial 16S rDNA sequencing, and hybridization analysis revealed the presence of DNA presumably representing a mixed bacterial flora in cholesterol gallstones, including H. pylori in the gallstone centres in 11 out of 20 patients. In three cases, the ureI-PCR assay revealed non-gastric H. pylori. Conclusions: These data support the presence of DNA from a mixed bacterial population, including H. pylori in cholesterol gallstones, reflecting either that H. pylori is an indigenous part of a flora in the stone-containing gallbladder or, alternatively, that H. pylori colonization in the biliary tract predisposes to cholesterol gallstone formation.

  • 12.
    Nilsson, B
    et al.
    Department of Surgery, Sahlgrenska University Hospital, Göteborg.
    Valantinas, J
    Centre of Hepatology, Gastroenterology and Dietetics, Clinic of Gastroenterology, Nephrourology and Surgery, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
    Hedin, L
    Friman, S
    Department of Transplantation and Liver Surgery, Sahlgrenska University Hospital, Göteborg,.
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Acetazolamide inhibits stimulated feline liver and gallbladder bicarbonate secretion2002Inngår i: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 174, nr 2, s. 117-123Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Bile acidification is a key factor in preventing calcium carbonate precipitation and gallstone formation. Carbonic anhydrase II (CA II), that is inhibited by acetazolamide, plays a role in regulation of the acid-base balance in many tissues. This study examines the effect of acetazolamide on secretin- and vasoactive intestinal peptide (VIP)-stimulated gallbladder mucosal bicarbonate and acid secretion. Gallbladders in anaesthetized cats were perfused with a bicarbonate buffer bubbled with CO2 in air. In 20 experiments VIP (10 ╡g kg1 h1) and in 10 experiments secretin (4 ╡g kg1 h1) were infused continuously intravenous (i.v.). Hepatic bile and samples from the buffer before and after perfusion of the gallbladder were collected for calculation of ion and fluid transport. During basal conditions a continuous secretion of H+ by the gallbladder mucosa was seen. Intravenous infusion of vasoactive intestinal peptide (VIP) and secretin caused a secretion of bicarbonate from the gallbladder mucosa (P < 0.01). This secretion was reduced by intraluminal (i.l.) acetazolamide (P < 0.01). Bile flow was enhanced by infusion of VIP and secretin (P < 0.01) but this stimulated outflow was not affected by i.v. acetazolamide. The presence of CA II in the gallbladder was demonstrated by immunoblotting. Biliary CA activity has an important function in the regulation of VIP- and secretin-stimulated bicarbonate secretion across the gallbladder mucosa.

  • 13.
    Nilsson, Isabelle
    et al.
    Linköpings universitet, Institutionen för medicin och vård. Linköpings universitet, Hälsouniversitetet.
    Shabo, Ivan
    Linköpings universitet, Institutionen för biomedicin och kirurgi. Linköpings universitet, Hälsouniversitetet.
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Monstein, Hans-Jurg
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för medicinsk cellbiologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Molekylärbiologiska tekniklaboratoriet.
    Multiple displacement amplification of isolated DNA from human gallstones: Molecular identification of Helicobacter DNA by means of 16S rDNA-based pyrosequencing analysis2005Inngår i: Helicobacter, ISSN 1083-4389, E-ISSN 1523-5378, Vol. 10, nr 6, s. 592-600Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. Molecular typing of Helicobacter spp. in clinical biopsy specimens has become increasingly important. By means of nested polymerase chain reaction (PCR) amplification and Southern blot analysis of the PCR amplicons, we have shown that Helicobacter spp. DNA is present in human gallstones. In this study we have investigated the possibility of using multiple displacement amplification (MDA) of isolated gallstone DNA and pyrosequencing analysis for the molecular identification of Helicobacter spp. Materials and Methods. DNA isolated from the nucleus of 33 human gallstones and one control strain were used in a MDA assay. Subsequently, pyrosequencing analysis was performed either directly on MDA-DNA using primers flanking the Helicobacter spp. 16S rDNA variable V3 region or on PCR amplicons derived from broad-range primers flanking the 16S rDNA variable V3, V4, and V9 regions. Results. Pyrosequencing analysis of 16S rDNA derived from MDA-DNA revealed that Helicobacter spp.-like DNA was present in 25 of 33 (approximately 76%) gallstones. Using an H. pylori-specific Southern blot analysis, Helicobacter spp.-like DNA was present in 20 of 33 [approximately 61%] of the gallstones. Using MDA-DNA directly in pyrosequencing analysis, Helicobacter spp.-like DNA was present in 13 of 33 [approximately 39%] gallstones. Conclusions. We conclude that multiple displacement amplification combined with pyrosequencing enables a rapid and accurate molecular typing of Helicobacter spp. from small and precious biopsy specimens. © 2005 The Authors Journal compilation © 2005 Blackwell Publishing Ltd.

  • 14.
    Sandstrom, Per
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Woods, C.M.
    Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Sciences, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
    Brooke-Smith, M.
    Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Sciences, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
    Saccone, G.T.P.
    Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Sciences, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
    Toouli, J.
    Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Sciences, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
    Svanvik, Joar
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Highly selective iNOS inhibition and sphincter of Oddi motility in the Australian possum2004Inngår i: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 181, nr 3, s. 321-331Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim:  Inducible nitric oxide synthase (iNOS) plays a major role in acute pancreatitis. Selective inhibitors of iNOS are being developed as therapeutic agents. Sphincter of Oddi (SO) dysfunction may cause pancreatitis and nitric oxide is necessary for SO relaxation. A new highly selective iNOS inhibitor, AR-C102222AA (AR-C), is evaluated together with the established iNOS inhibitor, l-N6-(1-iminoethyl)lysine (l-NIL), and the selective neuronal nitric oxide synthase (nNOS) blocker S-methyl-l-thiocitrulline (SMTC).

    Methods:  In anaesthetized Australian Brush-tailed possums, the effect of topical, i.v. or i.a. administration of these drugs was evaluated on spontaneous SO motility, blood pressure (BP) and pancreatic vascular perfusion. SO motility was recorded by manometry and pancreatic vascular perfusion by laser Doppler fluxmetry. Also, the effect of SMTC and AR-C on electrical field stimulation (EFS)-induced non-cholinergic non-adrenergic (NANC) SO relaxation in vitro was evaluated.

    Results:  Infusion of AR-C (0.1–30 μmol kg−1) increased SO contraction frequency (P = 0.026) only at the two highest doses. l-NIL infusion (0.15 to 14.7 μmol kg−1) also increased SO contraction frequency at 8.8 μmol kg−1 (P < 0.05) and reduced SO contraction amplitude at the two highest doses (P < 0.05). SMTC injections (0.5 nmol–2.4 μmol) produced a dose-dependent increase in SO contraction frequency (P = 0.009), but no effect was seen on the other parameters. In vitro SMTC (40–400 μm) inhibited EFS-induced NANC relaxation in a dose-dependent manner (P < 0.0005). In contrast AR-C (10–500 μm) had no effect on EFS-induced NANC relaxation (P > 0.05).

    Conclusions:  At low doses, AR-C does not effect SO motility or EFS-induced NO mediated relaxation. However, high doses of AR-C and L-NIL in vivo influenced SO motility by inhibiting nNOS activity and these effects need be considered in relation to therapeutic doses of this agent.

  • 15.
    Sandström, Per
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Brooke-Smith, Mark E
    Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Sciences, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
    Thomas, Anthony C
    Department of Anatomical Pathology, Flinders Medical Centre, Flinders University of South Australia, Adelaide, SA, Australia.
    Grivell, Marlene B
    Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Sciences, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
    Saccone, Gino T P
    Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Sciences, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
    Toouli, James
    Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Sciences, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
    Svanvik, Joar
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Highly selective inhibition of inducible nitric oxide synthase ameliorates experimental acute pancreatitis2005Inngår i: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 30, nr 1, s. 10-15Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES:

    Inducible nitric oxide synthase (iNOS) activity is increased in experimental acute pancreatitis. The aim of this study was to evaluate treatment with the selective iNOS inhibitors AR-C (AR-C102222AA) and L-NIL (L-N6-(1-iminoethyl)-lysine) in experimental acute pancreatitis.

    METHODS:

    Acute pancreatitis was induced in anesthetized Australian possums by topical administration of carbachol on the sphincter of Oddi. AR-C treatment was 2 intravenous infusions (2.5 micromol/kg over 15 minutes) at 2 and 4 hours after acute pancreatitis induction. L-NIL treatment was an intraarterial infusion (1 mg/kg/h) from 2 hours after acute pancreatitis induction. At 8 hours, pancreatic tissue was harvested and inflammation assessed (histologic score). Blood samples were collected for plasma amylase, lipase, and amino acid levels. Blood pressure, central venous pressure, supplementary fluids, and urine output were monitored.

    RESULTS:

    Treatment with AR-C or L-NIL reduced the plasma levels of amylase and the volume of supplementary fluids and improved the histological score (all P < 0.05). In animals with acute pancreatitis, plasma arginine levels were reduced (P < 0.05), while citrulline and ornithine levels increased (P < 0.05), consistent with increased nitric oxide production. Treatment with AR-C ameliorated the reduced arginine level.

    CONCLUSIONS:

    Treatment with AR-C or L-NIL, commencing 2 hours after the induction of acute pancreatitis, has significant and beneficial effects in experimental acute pancreatitis in Australian possums.

  • 16.
    Sandström, Per
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Gasslander, Thomas
    Department of Surgery, Vrinnevi Hospital, Norrköping, Sweden.
    Sundqvist, Tommy
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Franke, Jonas
    Department of Surgery, Vrinnevi Hospital, Norrköping, Sweden.
    Svanvik, Joar
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Depletion of serum L-arginine in patients with acute pancreatitis2003Inngår i: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 27, nr 3, s. 261-266Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Acute pancreatitis may be initiated by interference with the pancreatic outflow to the duodenum. This flow is normally regulated by reflex relaxation of the sphincter of Oddi in which nitric oxide is an important mediator.

    Aim: To test the hypothesis that acute pancreatitis involves a depletion in serum l-arginine resulting in impaired production of nitric oxide.

    Methods: We measured serum l-arginine and l-citrulline and urinary nitrite/nitrate concentrations 1 to 3 days after the onset of symptoms in 11 patients with gallstone pancreatitis, 10 patients with alcoholic pancreatitis, and 6 patients with idiopathic pancreatitis. We compared their results with those from control groups of 13 healthy blood donors, 9 patients fasting before hernia operations, 8 patients with acute cholecystitis, and 9 alcoholic subjects but no pancreatitis. Serum arginine and citrulline concentrations were measured with high performance liquid chromatography, and urinary nitrite/nitrate spectrophotometrically.

    Results: Patients with acute pancreatitis, of whatever cause, had lower serum l-arginine and l-citrulline concentrations than controls. Patients with gallstone and idiopathic pancreatitis also have reduced urinary concentrations of nitrite and nitrate but this was not seen in patients with alcoholic pancreatitis.

    Conclusions: L-arginine and l-citrulline concentrations are depleted in the serum of patients with acute pancreatitis. Reduced urinary nitrite and nitrate in gallstone pancreatitis indicate that there is a defect formation of nitric oxide. This may cause a functional obstruction of the outflow of pancreatic juice to the duodenum and so may be involved in the pathophysiology of acute pancreatitis.

  • 17.
    Sandström, Per
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Trulsson, Lena
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi.
    Gasslander, Thomas
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Sundqvist, Tommy
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi.
    von Dobeln, U.
    Department of Laboratory Medicine Karolinska University Hospital Huddinge, Stockholm.
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Serum amino acid profile in patients with acute pancreatitis2008Inngår i: Amino Acids, ISSN 0939-4451, E-ISSN 1438-2199, Vol. 35, nr 1, s. 225-231Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Patients in the early phase of acute pancreatitis (AP) have reduced serum levels of arginine and citrulline. This may be of patho-biological importance, since arginine is the substrate for nitric oxide, which in turn is involved in normal pancreatic physiology and in the inflammatory process. Serum amino acid spectrum was measured daily for five days and after recovery six weeks later in 19 patients admitted to the hospital for acute pancreatitis. These patients had abnormal levels of most amino acids including arginine, citrulline, glutamine and glutamate. Phenylalanine and glutamate were increased, while arginine, citrulline, ornithine and glutamine were decreased compared to levels after recovery. NO2/NO3 concentration in the urine, but not serum arginase activity, was significantly increased day 1 compared to day 5 after admission. Acute pancreatitis causes a disturbance of the serum amino acid spectrum, with possible implications for the inflammatory process and organ function both in the pancreas and the gut. Supplementation of selected amino acids could possibly be of value in this severe condition. © 2007 Springer-Verlag.

  • 18.
    Shabo, Ivan
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi.
    Nordenskjöld, Kerstin
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Incidensen av gallblåsecancer i Sverige har minskat. Den dåliga prognosen kan möjligen förbättras genom radikal kirurgi. [The incidence of gallbladder cancer in Sweden has decreased. The poor prognosis can possibly be improved by radical surgery.]2001Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 98, nr 42, s. 4584-4589Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [sv]

    Gallblåsecancer är en relativt sällsynt sjukdom som har dålig prognos med kort överlevnadstid. Sjukdomen drabbar framför allt kvinnor. Vi har inhämtat registerdata från cancerregistret och dödsorsaksregistret och studerat utvecklingen i Sverige mellan 1988 och 1997. Under de senaste åren har incidensen minskat, vilket möjligen kan förklaras av en hög kolecystektomifrekvens under 1950- och 1970-talen. Prognosen vid erhållen diagnos har tidigare varit dålig, med en medianöverlevnad på 3,5 månader, vilket beror på att diagnosen ofta har ställts först när sjukdomen blivit avancerad. Epidemiologiska data visar att dessa siffror kan ha förbättrats de senaste åren. I flera aktuella studier, framför allt från Japan, rapporteras bättre resultat och längre överlevnadstid efter utvidgad kirurgi. I ett material av elva patienter med gallblåsecancer, grad II–V enligt Nevin, som opererats med utvidgad kirurgi i Linköping finns hos tio inga tecken på recidiv efter en uppföljningstid på 1–8 år.

  • 19.
    Shabo, Ivan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Olsson, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Elkarim, Rihab
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Svanvik, Joar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Macrophage Infiltration in Tumor Stroma is Related to Tumor Cell Expression of CD163 in Colorectal Cancer2014Inngår i: Cancer Microenvironment, ISSN 1875-2292, E-ISSN 1875-2284, Vol. 7, nr 1, s. 61-69Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The scavenger receptor, CD163, is a macrophage-specific marker. Recent studies have shown that CD163 expression in breast and rectal cancer cells is associated with poor prognosis. This study was conducted to evaluate the relationship between CD163 expression as a macrophage trait in cancer cells, and macrophage infiltration and its clinical significance in colorectal cancer. Immunostaining of CD163 and macrophage infiltration were evaluated in paraffin-embedded specimens, earlier analyzed for CD31, D2-40 and S-phase fraction, from primary tumors and normal colorectal mucosa of 75 patients with colorectal carcinoma. The outcomes were analyzed in relation to clinical-pathological data. CD163 expression was positive in cancer cells in 20 % of colorectal cancer patients and was related to advanced tumor stages (P = 0.008) and unfavorable prognosis (p = 0.001). High macrophage infiltration was related to shorter survival and positive CD163 expression in tumor cells. The prognostic impact of macrophage infiltration was independent of tumor stage and CD163 expression in cancer cells (p = 0.034). The expression of macrophage phenotype in colorectal cancer cells is associated with macrophage density in tumor stroma and lower survival rates. Macrophage infiltration has an independent prognostic impact on mortality in colorectal cancer. In accordance with previous experimental studies, these findings provide new insights into the role of macrophages in colorectal cancer.

  • 20.
    Shabo, Ivan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Olsson, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Svanvik, Joar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Breast Cancer Expression of DAP12 is Associated With Skeletal and Liver Metastases and Poor Survival2013Inngår i: Clinical Breast Cancer, ISSN 1526-8209, E-ISSN 1938-0666, Vol. 13, nr 5, s. 371-377Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Macrophages are an important cellular factor in breast cancer (BRC) progression and metastasis. DNAX activating protein of 12 kD (DAP12) is essential factor for macrophage fusion function. This study was conducted to investigate the expression and significance of DAP12 expression in BRC. DAP12 is expressed in BRC cells and associated with poor survival, liver metastases, and bone metastases. These data provide new insight into the pathophysiology of macrophages in BRC. less thanbrgreater than less thanbrgreater thanBackground: The transmembrane adapter protein, DAP12, transduces activation signals for several arrays of receptors, including human signal-regulatory protein, DAP12-associating lectin-1, triggering receptor expressed on myeloid cells-1, -2, and -3, in natural killer cells, granulocytes, monocytes/macrophages, and dendritic cells. The macrophage-specific antigen, Cluster of Differentiation 163 (CD163), is expressed in breast and colorectal cancers and is associated with early cancer recurrence and poor prognosis. It was recently shown that fusion between intestinal tumor cells and macrophages results in nuclear reprogramming with hybrid transcripts from both cells of origin. The role of DAP12 in the fusion process is not known. This study investigates the expression of DAP12 in BRC cells, and its relation to other macrophage traits and to the clinical progression of disease. Materials and Methods: Immunostaining of DAP12 and CD163 was performed and evaluated in paraffin-embedded specimens from 132 patients with BRC. The outcomes were analyzed in relation to clinicopathological data. Results: DAP12 expression in cancer cells was positive in 66 percent of the cancers and was associated with high tumor grade (P = .015), and with liver (P = .047) and skeletal (P = .067), but not with lung metastases (P = 1.00). Patients with BRC expressing DAP12 had poor prognosis, with higher recurrence rates of skeletal (P = .018) and liver metastases (P = .047), and shorter survival time (P = .0060). Conclusion: We suggest that macrophage traits in BRC cells facilitate the metastatic process and that DAP12 expression might promote metastatic homing to bone and liver tissues.

  • 21.
    Shabo, Ivan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiskt centrum.
    Olsson, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och klinisk genetik.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiskt centrum.
    Svanvik, Joar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiskt centrum.
    DAP12, a macrophage fusion receptor, is expressed in breast cancer cells and associated with skeletal and liver metastases and poor survivalManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    DAP12 is a transmembrane receptor present in myeloid cells and is essential for the development of functionally mature osteoclasts and microglia, and for integrin signaling in macrophages and neutrophils. The macrophage specific antigen CD163 is expressed in breast and colorectal cancer and is associated with early cancer recurrence and poor prognosis. We hypothesize that macrophage traits in cancer cells may be explained by fusion between cancer cells and tumor associated macrophages. The role of DAP12 in the fusion between cancer cells and macrophages is not known. This study was performed to investigate the expression of DAP12 in breast cancer cells and its´ relation to macrophage trait manifested by CD163 expression.

    Immunostaining of DAP12, CD163 and MAC387 were evaluated in paraffinembedded specimens from totally 133 patients with breast cancer. The outcomes were analyzed in relation to clinicopathological data.

    DAP12 expression was positive in the majority of cases (64%) with breast cancer and associated with advanced tumor grade (p= 0.015) and liver metastasis (p= 0.0465) but not lung metastasis (0.997). It tended to correlate with skeletal metastases (p=0.0673). Patients with breast cancer expressing high DAP12 had poor prognosis with higher rates of skeletal (p=0.023) and liver metastases (p=0.028) and overall shorter distant recurrence free survival (p=0.0028). DAP12 expression was neither correlated to CD163 nor MAC387 expression. To our knowledge, this is the first study where DAP12 expression is reported in breast cancer.

    In conclusion, DAP12 is expressed in breast cancer and is significantly related to skeletal and liver metastasis as well as poor prognosis. We hypothesize that DAP12 expression may promote fusion between breast cancer cells and macrophages. It may even promote homing of cancer cells in bone and liver tissue and result in increased metastasis at these sites.

  • 22.
    Shabo, Ivan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Olsson, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Svanvik, Joar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time.2009Inngår i: International journal of cancer. Journal international du cancer, ISSN 1097-0215, Vol. 125, nr 8, s. 1826-1831Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Expression of the macrophage antigen CD163 in breast cancer cells is recently shown to be related to early distant recurrence and shortened survival. In this study, 163 patients with rectal cancer, included in the Swedish rectal cancer trial and followed up for a median of 71 months, were examined for the expression of CD163 in the primary tumors. The cancer cells expressed CD163 in the primary tumors in 23% (n = 32) of the patients. In pretreatment biopsies from 101 patients, 10 had CD163-positive cancers and these patients had earlier local recurrence (p < 0.044) and reduced survival time (p < 0.045) compared with those with CD163-negative tumors. When studying surgical specimens from 61 patients randomized to preoperative irradiation (5 x 5 Gy delivered in 1 week), it was found that 31% were CD163 positive whereas the corresponding figure was only 17% for 78 patients who were nonirradiated (p < 0.044), which tentatively may be consistent with X-rays inducing fusion. In CD163-positive tumors there was a reduced apoptotic activity as measured with the Termina deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) technique (p = 0.018). There tended also to be an increased proliferation activity measured as an expression of Ki-67 non significant (NS). It is concluded that primary rectal cancers may express CD-163, and this phenotypic macrophage trait is related to early local recurrence, shorter survival time and reduced apoptosis. Furthermore, the expression of CD163 is more common after irradiation.

  • 23.
    Shabo, Ivan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Olsson, Hans
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Linköpings universitet, Hälsouniversitetet.
    Doré, Siv
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Linköpings universitet, Hälsouniversitetet.
    Svanvik, Joar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival2008Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 123, nr 4, s. 780-786Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cells of the monocyte/macrophage lineage are important for tumour cell migration, invasion and metastasis. Fusion between macrophages and cancer cells in animal models in vitro and in vivo causes hybrids with increased metastatic potential. Primary breast cancer cells were characterized for macrophage antigens to test if phenotypic resemblance to macrophages is related to early distant recurrence. Immunostaining for CD163, MAC387 and CD68 was performed in a breast cancer tissue micro array from 127 patients consequently followed up for a median of 13 years. Tumour-associated macrophages expressed all 3 antigens. The breast cancers expressed CD163 to 48%, MAC387 to 14% while CD68 was not expressed. TGF-β staining intensity was positively related to both CD163 and MAC387 expression. Expression of CD163 in the cancer cells was compared to their DNA ploidy, Nottingham Histological Grade, TNM-stage, node state, presence of estrogen receptors and occurrence of distant metastases and survival. Cancers of a more advanced histological grade expressed CD163 to a higher extent. Cells expressing MAC387 were more common in cancers with a high proportion of CD163 positive cells. Multivariate analysis showed that expression of the macrophage antigen CD163 in breast cancer cells has a prognostic impact on the occurrence of distant metastases and reduced patient survival time.

  • 24.
    Shabo, Ivan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken i Östergötland.
    Svanvik, Joar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken i Östergötland.
    Expression of Macrophage Antigens by Tumor Cells2011Inngår i: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 714, s. 141-150Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Macrophages are a heterogeneous cell population of the myeloid linage derived from monocytes. These cells show two different polarization states, M1 and M2 macrophages in response to different micro environmental signals. Tumor associated macrophages (TAM) represent the M2 type and promote tumor progression. These cells express antigens that more or less are specific for macrophages like: CD14, CD68, MAC387, CD 163, and DAP12. In a series of recent studies it is shown that cancer cells may express these antigens and CD I 63, MAC387 and DAP12 may be expressed by e.g. breast cancer cells. Thus, 48% of the breast cancers expressed CD163 that is a scavenger receptor normally expressed by macrophages alone. The corresponding figure for rectal cancer is 31%. The expression of CD163 is correlated to early distant recurrence in breast cancer and local recurrence in rectal cancer and reduced survival time in both conditions. Expression of macrophage antigens in breast- and colorectal-cancers may have a prognostic relevance in clinical praxis. One explanation to these findings is that resemblance with macrophages may indicate a more invasive phenotype due to genetic exchange between the primary tumor cells and associated macrophages. This is further supported by the finding that expression of DAP12, a macrophage fusion receptor, in breast cancer is associated with an advanced tumor grade and higher rates of skeletal and liver metastases and overall shorter distant recurrence free survival. Another explanation to the changed phenotype is a genetic exchange between the cells by exosome-mediated transfer.

  • 25.
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    För en säkrare vård: Analysera den "mänskliga faktorn"! [For safer health care: Analyse the "human factor"!]2001Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 98, s. 3770-3771Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [sv]

    Genom att utnytja erfarenheter inom andra verksamheter med högt ställda säkerhetskrav bör vi kunna göra vården säkrare. Förebyggande riskhantering kan ske genom analys av mänskliga felhandlingar, dels som generell vetenskap dels som en erfarenhetsregistrering, på ett sätt som minskar risken för att misstag skall upprepas. Den tekniska utvecklingen har skapat möjligheter för övning av färdigheter i realistiska simuleringsmodeller. Detta är användbart för övning av bl a kirurger, ortopeder och anestesiologer och kan även användas för rehabilitering av patienter.

  • 26.
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Gallsten - riskfaktorer och komplikationer.2000Inngår i: Incitament, ISSN 1103-503X, Vol. 9, s. 575-580Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 27.
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Laparoscopic cholecystectomy for acute cholecystitis2000Inngår i: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 165, s. 16-17Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Acute cholecystitis was initially considered a contra-indication for laparoscopic cholecystectomy, but today the laparoscopic route is generally used even for severe acute cholecystitis. Several studies have shown that this is possible, although the conversion and complication rates are high, but there are no randomised controlled trials that evaluate the complications and costs of this technique compared with conventional open techniques. The timing of a laparoscopic cholecystectomy for acute cholecystitis is also a matter of debate as well as its use in elderly patients with this condition.

  • 28.
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Laparoscopic cholecystectomy for acute cholecystitis1999Inngår i: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 166, nr Suppl. 585, s. 16-17Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Acute cholecystitis was initially considered a contra-indication for laparoscopic cholecystectomy, but today the laparoscopic route is generally used even for severe acute cholecystitis. Several studies have shown that this is possible, although the conversion and complication rates are high, but there are no randomised controlled trials that evaluate the complications and costs of this technique compared with conventional open techniques. The timing of a laparoscopic cholecystectomy for acute cholecystitis is also a matter of debate as well as its use in elderly patients with this condition.

  • 29.
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    ... och därför blev Kibor "hittad på vägen" läkare2005Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 102, nr 34, s. 2320-2321Artikkel i tidsskrift (Annet vitenskapelig)
  • 30.
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Patienten från Turkana [A patient from Turkana]2004Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, nr 51-52, s. 4214-4215Artikkel i tidsskrift (Annet vitenskapelig)
  • 31.
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Results of laparoscopic compared with open cholecystectomy2000Inngår i: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 165, s. 12-15Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Laparoscopic cholecystectomy was introduced in 1985 and diffused within a few years throughout the world. The avalanche-like spread resulted in this procedure not being scientifically supported by results of controlled clinical trials. By 1997 there were just 13 randomised controlled trials and 150 prospective studies that followed a research protocol, while there were more than 1500 retrospective analyses of series of operations in a country, in a specific hospital, or by a specific surgeon. Comparisons with the conventional laparotomy technique and with minilaparotomy techniques are complicated by the fact that the variables compared, such as operation times, complication rates, and costs, varied over time.

  • 32.
    Svanvik, Joar
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Arvidsson, Dag
    Evaluation of laparoscopic procedures in the treatment of biliary disease, gastro-eosophageal reflux and inguinal hernia. State-of-the-art-konferens.2000Inngår i: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 166Artikkel i tidsskrift (Fagfellevurdert)
  • 33.
    Trulsson, Lena
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi.
    Gasslander, Thomas
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Permerth, J
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    The balance of mitogenesis and apoptosis in the rat pancreas in response to CCK-8.2000Inngår i: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 118, nr 4, s. 5324-Konferansepaper (Annet vitenskapelig)
  • 34.
    Trulsson, Lena
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Gasslander, Thomas
    Department of Surgery, Vrinnevi Hospital, Norrköping, Sweden.
    Sundqvist, Tommy
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Svanvik, Joar
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    The influence of nitric oxide on basal and cholecystokinin-8-induced proliferation and apoptosis in the rat pancreas2002Inngår i: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 106, nr 1-3, s. 97-104Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Nitric oxide (NO) is formed by different cell types in the pancreas. In this study, inhibition of endogenous nitric oxide by Nω-nitro-l-arginine (l-NNA) reduced the urinary excretion of NO2/NO3 and raised serum l-arginine and the NO donator S-nitroso-N-acetylpenicillamine (SNAP) increased the urinary excretion of NO2/NO3. The peptide cholecystokinin-8 (CCK-8) has a strong influence on exocrine pancreatic proliferation. Rat pancreas was excised and studied with regard to tissue weight, protein and DNA contents after 3 days of treatment with saline, l-NNA or SNAP given separately or combined with CCK-8. Further, proliferation of different pancreatic cells was studied with [3H]-thymidine incorporation and apoptotic activity was studied by analysing caspase-3 activity and histone-associated DNA fragments. The effects of l-NNA indicate that endogenous nitric oxide formation has a tonic inhibition on apoptosis in the pancreas during both basal condition and growth stimulation by CCK-8. In CCK-induced hyperplasia, NO inhibits the proliferation of acinar cells but stimulates ductal cells. Endogenous NO may regulate the balance between proliferation and apoptosis and in a situation of growth stimulation by CCK-8, it has a tonic inhibition on both mitogenesis and apoptosis thus slowing down the acinar cell turnover in the pancreas.

  • 35.
    Trulsson, Lena
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi.
    Gasslander, Thomas
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Cholecystokinin-8-induced hypoplasia of the rat pancreas: Influence of nitric oxide on cell proliferation and programmed cell death2004Inngår i: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 95, nr 4, s. 183-190Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The background of cholecystokinin-8 (CCK-8)-induced hypoplasia in the pancreas is not known. In order to increase our understanding we studied the roles of nitric oxide and NF-κB in rats. CCK-8 was injected for 4 days, in a mode known to cause hypoplasia, and the nitric oxide formation was either decreased by means of Nω-nitro-L-arginine (L-NNA) or increased by S-nitroso-N-acetylpencillamine (SNAP). The activation of NF-κB was quantified by ELISA detection, apoptosis with caspase-3 and histone-associated DNA-fragmentation and mitotic activity in the acinar, centroacinar and ductal cells were visualized by the incorporation of [3H]-thymidine. Pancreatic histology and weight as well as protein- and DNA contents were also studied. Intermittent CCK injections reduced pancreatic weight, protein and DNA contents and increased apoptosis, acinar cell proliferation and nuclear factor κB (NF-κB) activation. It also caused vacuolisation of acinar cells. The inhibition of endogenous nitric oxide formation by L-NNA further increased apoptosis and NF-κB activation but blocked the increased proliferation and vacuolisation of acinar cells. The DNA content was not further reduced. SNAP given together with CCK-8 increased apoptosis and other pathways of cell death, raised proliferation of acinar cells and strongly reduced the DNA content in the pancreas. Histological examination showed no inflammation in any group. We conclude that during CCK-8-induced pancreatic hypoplasia, endogenously formed nitric oxide suppresses apoptosis but increases cell death along non-apoptotic pathways and stimulates regeneration of acinar cells. Exogenous nitric oxide enhances the acinar cell turnover by increasing both apoptotic and non-apoptotic cell death and cell renewal. In this situation NF-κB activation seems not to inhibit apoptosis nor promote cell proliferation.

  • 36.
    Trulsson, Lena M.
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Gasslander, Thomas
    Department of Surgery, Vrinnevi Hospital, Norrköping, Sweden.
    Svanvik, Joar
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Cholecystokinin-8-induced atrophy in the rat pancreas: influence of nitric oxide on proliferation, programmed cell death and NF-κB activationManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The mechanisms involved in cholecystokinin-8-induced atrophy in the pancreas are not known and in this study the roles of nitric oxide (NO) and NF-κB were studied in rats. CCK-8 was injected for 4 days, in a mode known to cause atrophy, and the NO formation was either decreased by Nω-nitro-L-arginine (L-NNA) or increased by S-nitroso-N-acetylpencillamine (SNAP). Activation of NF-κB was quantified by ELISA detection, apoptosis with caspase-3 and histone associated DNA-fragmentation and mitotic activity in the acinar, centroacinar and ductal cells was visualized by incorporation of [3H]-thymidine. Pancreatic histology, weight, protein- and DNA contents were studied.

    Intermittent CCK injections reduced pancreatic weight, protein and DNA contents and increased apoptosis, acinar cell proliferation and NF-κB activation. It also caused vacuolisation of the acinar cells. Inhibition of endogenous NO formation by L-NNA further increased apoptosis and NF-κB activation but blocked the increased proliferation and vacuolisation of acinar cells. The DNA content was not further reduced. SNAP given together with CCK-8 increased both apoptosis and proliferation of acinar cells and strongly reduced the DNA content in the pancreas. Further, it caused vacuolisation in the acinar cells and these findings together indicate cell death by other pathways besides apoptosis. Histological examination showed no inflammation in any group.

    During CCK-8 induced pancreatic atrophy endogenous NO suppresses apoptosis and stimulates regeneration of acinar cells but increases cell death by non-apoptotic pathways. Exogenous NO enhances the acinar cell turnover by increases of both proliferation and apoptotic and non-apoptotic cell deaths. NF-κB activation, in this situation, seems not to inhibit apoptosis or promote cell proliferation.

  • 37.
    Trulsson, Lena M.
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Svanvik, Joar
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Permert, Johan
    Department of Surgery, Karolinska Institute at Huddinge, Huddinge University Hospital, Stockholm, Sweden.
    Gasslander, Thomas
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Cholecystokinin octapeptide induces both proliferation and apoptosis in the rat pancreas2001Inngår i: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 98, nr 1-2, s. 41-48Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cholecystokinin-8 (CCK-8) causes exocrine pancreatic hypertrophy and hyperplasia. High doses of the CCK analogue cerulein causes necrosis and an inflammatory response in the pancreas. We have studied the pancreatic growth response in rats after administration of CCK-8 for 3 days, given either intermittently (20–80 μg/kg) twice a day, or continuously (2.4–48 μg/kg per 24 h). Plasma CCK-8 levels, pancreatic wet weight, water, protein and DNA contents and the pancreatic caspase-3 activity were measured. Cell proliferation was visualized by [3H]thymidine incorporation and apoptosis by TUNEL reaction. Continuous administration of CCK-8 dose-dependently increased the plasma CCK levels, the pancreatic wet weight, protein and DNA contents as well as thymidine labeling index, apoptotic index and caspase-3 activity. Intermittent injections of CCK-8 caused transient raises in plasma CCK, increased apoptotic index and caspase-3 activity, a dose-dependent increase in thymidine labeling but caused a dose-dependent reduction of pancreatic wet weight, protein, and DNA contents. It is concluded that CCK-8 causes both increased proliferation and apoptosis in the pancreas. In case of continuous administration of CCK-8, the proliferation outweighs the apoptosis causing hyperplasia but in the case of intermittent administration the opposite effect is seen.

  • 38.
    Trulsson, Lena
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Sandström, Per
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Sundqvist, Tommy
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Smeds, Staffan
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Gasslander, Thomas
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Svanvik, Joar
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    The influence of a load of L-arginine on serum amino acids and pancreatic apoptosis/proliferation and ATP levels in the rat2004Inngår i: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 29, nr 4, s. 113-120Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES:

    Administration of high doses of amino acids like ethionine, methionine, and arginine causes pancreatic tissue damage. The initial mechanism behind these effects is not known. The aim of this study was to show the early effects of a load of L-arginine on programed cell death/proliferation and ATP levels in the pancreas.

    METHODS:

    We analyzed in rats the effects of intraperitoneal administration of L-arginine on serum amino acids, pancreatic cell apoptosis/proliferation, and ATP levels at 8, 16, and 24 hours. Serum amino acid concentrations were measured with HPLC, tissue ATP was measured fluorometrically, apoptosis was studied with caspase-3 activity and histone-associated DNA-fragments, and proliferation was studied with thymidine autoradiography.

    RESULTS:

    After a load of l-arginine, there were initially increased serum levels of L-arginine and L-citrulline, but these fell below control levels after 24 hours as well as amino acids in the glutamate family (ornithine, proline, histidine, and glutamine). Initially, increased ATP levels in the pancreatic tissue returned to control levels at 24 hours. The acinar cells proliferation was suppressed and the apoptosis rate strongly increased at 16 and 24 hours. Pancreatic histology showed vacuole formation in the acinar cells at 8 hours. At 16 hours, there was less vacuolization, but apoptotic bodies were seen, and at 24 hours there was cell degeneration but no necrosis.

    CONCLUSIONS:

    After a load of l-arginine, amino acid metabolism causes a high ATP production in the pancreatic tissue that may cause mitochondrial initiation of cell death.

  • 39.
    Wallin, Åsa
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Francis, P.
    Department of Oncology, Institute of Clinical Sciences, Lund University, Lund, Sweden.
    Nilbert, N.
    Department of Oncology, Institute of Clinical Sciences, Lund University, Lund, Sweden.
    Svanvik, Joar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Gene expression profile of colon cancer cell lines treated with SN-382010Inngår i: Chemotherapy, ISSN 0009-3157, E-ISSN 1421-9794, Vol. 56, nr 1, s. 17-25Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: Colorectal cancer is the third most common form of cancer in the industrialcountries. Due to advances regarding the treatments, primarily development ofimproved surgical methods, and the ability to make the earlier diagnosis, the mortalityhas remained constant during the past decades even though the incidence in fact hasincreased. To improve chemotherapy and enable personalised treatment, the need ofbiomarkers is of great significance. In this study we evaluated the gene expressionprofiles of the colon cancer cell lines treated with SN-38, the active metabolite oftopoisomerase-1 inhibitor irinotecan which leads to cell cycle arrest and apoptosis.Material and Methods: The study included three colon cancer cell lines KM12C,KM12SM and KM12l4a. The three cell lines were treated with SN-38, and sampleswere obtained after 24 and 48 hour treatments. The gene expression analyses wereperformed using oligonucleotide microarrays comprising of ~27,000 spots where theuntreated controls were compared to the SN-38 treated samples. Results: Unsupervisedclustering clearly distinguished the treated cell lines from the untreated. Supervisedanalysis identified 3974 significant genes (p=0.05) differentiating the treated samplesfrom the untreated, majority of which were downregulated after treatment. The toprankeddownregulated genes in the treated cell lines included those related to receptorand kinase activity, signal transduction, apoptosis, RNA processing, protein metabolismand transport, cell cycle and transcription. A smaller number of genes were upregulatedin the cell lines after treatment and included genes involved in apoptosis, transcription,development and differentiation. Conclusions: These results demonstrate that theexpression of the genes involved in cell proliferation and apoptosis as well as RNA,DNA and protein metabolism were affected by SN-38. The impact of certain genes oncolorectal cancer development needs to be further evaluated, however these resultscould serve as a basis for further studies in order to find targets for irinotecan treatment.

  • 40.
    Wallin, Åsa R.
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Svanvik, Joar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Adell, Gunnar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Expression of PRL proteins at invasive margin of rectal cancers in relation to preoperative radiotherapy2006Inngår i: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 65, nr 2, s. 452-458Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: PRL-3 (phosphatase of regenerating liver) is involved in metastasis of colorectal cancer; however, its therapeutic implication in cancer patients has not been studied. We investigated the relationships of PRL expression to radiotherapy (RT) in rectal cancer patients.

    Methods and Materials: Phosphatase of regenerating liver expression was immunohistochemically examined in distant (n = 36) and adjacent (n = 82) normal mucosa, primary tumor (n = 125), biopsy specimens (n = 96), and lymph node metastasis (n = 30) from rectal cancer patients participating in a clinical trial of preoperative RT.

    Results: Phosphatase of regenerating liver expression was increased from the distant to adjacent mucosa and to the primary tumor (p < 0.05). PRL was highly expressed at the invasive margin in 28% of the primary tumors and 26% of the metastases. In the RT group, strong PRL expression at the invasive margin was related to distant recurrence (p = 0.006) and poor survival (p = 0.01), but not in the non-RT group. The survival significance remained even after adjusting for Dukes’ stage and differentiation (p = 0.02). Additional multivariate analyses showed that the correlation with prognostic significance of PRL differed between the RT and non-RT groups (p = 0.01).

    Conclusion: Phosphatase of regenerating liver expression (rather than PRL-3 alone) at the invasive margin predicted resistance to RT and unfavorable survival in rectal cancer patients with preoperative RT.

  • 41.
    Wallin, Åsa
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Svanvik, Joar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Holmlund, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Ferreud, Lillianne
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Anticancer effect of SN-38 on colon cancer cell lines with different metastatic potential2008Inngår i: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 19, nr 6, s. 1493-1498Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    SN-38 is an active metabolite of the topoisomerase I inhibitor irinotecan. The mechanism behind its antitumor effect in colorectal cancer is not fully understood. In this study, we examined the response of colon cancer cell lines with different metastatic potential to SN-38. The parental human colon cancer cell line KM12C and its two highly metastatic derivatives KM12SM and KM12L4a were cultivated in 5% CO2 at 37°C for 24 h and then exposed to SN-38 (2.5 µg/ml) at 37°C for 4, 24 and 48 h, respectively. The cell cycle was measured by flow cytometry, apoptotic activity was determined by flow cytometry and immunocytochemistry and the expression of topoisomerase I, Bax and survivin proteins were examined by Western blot. The exposure of the cells to SN-38 induced S-phase and G2 arrest (P<0.0001) and the KM12L4a cells had the highest response in a time-dependent manner (P<0.0001). The rates of apoptosis in the KM12SM (P=0.001) and KM12L4a cell lines (P=0.01) were increased time-dependently, though there was no such change in the KM12C cells. The expression of topoisomerase I protein was decreased in each cell line tested and the expression of Bax protein was increased, especially in KM12L4a. In conclusion, the effect of SN-38 on the colon cancer cell lines was mediated via conducting S-phase and G2 arrest and apoptosis. This effect was found in the cell lines with higher metastatic potentials, indicating that SN-38 can be used to treat advanced colon cancers.

  • 42.
    Winbladh, Anders
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Gullstrand, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Svanvik, Joar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Sandström, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Systematic review of cholecystostomy as a treatment option in acute cholecystitis2009Inngår i: HPB, ISSN 1365-182X, Vol. 11, nr 3, s. 183-193Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Objectives: Percutaneous cholecystostomy (PC) is an established low-mortality treatment option for elderly and critically ill patients with acute cholecystitis. The primary aim of this review is to find out if there is any evidence in the literature to recommend PC rather than cholecystectomy for acute cholecystitis in the elderly population. Methods: In April 2007, a systematic electronic database search was performed on the subject of PC and cholecystectomy in the elderly population. After exclusions, 53 studies remained, comprising 1918 patients. Three papers described randomized controlled trials (RCTs), but none compared the outcomes of PC and cholecystectomy. A total of 19 papers on mortality after cholecystectomy in patients aged greater than65 years were identified. Results: Successful intervention was seen in 85.6% of patients with acute cholecystitis. A total of 40% of patients treated with PC were later cholecystectomized, with a mortality rate of 1.96%. Procedure mortality was 0.36%, but 30-day mortality rates were 15.4 % in patients treated with PC and 4.5% in those treated with acute cholecystectomy (P less than 0.001). Conclusions: There are no controlled studies evaluating the outcome of PC vs. cholecystectomy and the papers reviewed are of evidence grade C. It is not possible to make definitive recommendations regarding treatment by PC or cholecystectomy in elderly or critically ill patients with acute cholecystitis. Low mortality rates after cholecystectomy in elderly patients with acute cholecystitis have been reported in recent years and therefore we believe it is time to launch an RCT to address this issue.

  • 43.
    Winbladh, Anders
    et al.
    Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala. Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Sandström, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Olsson, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och klinisk genetik.
    Svanvik, Joar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Gullstrand, P
    Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Segmental ischemia of the liver - microdialysis in a novel porcine model.2009Inngår i: European surgical research. Europäische chirurgische Forschung. Recherches chirurgicales européennes, ISSN 1421-9921, Vol. 43, nr 3, s. 276-285Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Segmental liver ischemia is often used in rodents to study ischemia and reperfusion injuries (IRI). There are no reports of protocols using segmental ischemia in porcine models. Microdialysis (MD) provides the opportunity to study local effects of IRI in vivo. METHODS: Eight pigs received an MD catheter placed in liver segments IV and V, respectively. All circulation to segment IV was stopped for 80 min, and reperfusion was followed for 240 min. RESULTS: During ischemia the levels of lactate, glycerol and glucose increased 3-fold (p < 0.001), 40-fold (p < 0.001) and 4-fold (p < 0.01), respectively, in the ischemic segment compared to the perfused segment, whereas the levels of pyruvate fell to a tenth of the preischemic level (p < 0.001). All values returned to baseline after reperfusion. Serum levels of aspartate aminotransferase increased (p < 0.05). Polymorphonuclear cells increased in both segments, although the density was significantly higher in segment IV. CONCLUSION: Clamping of one liver segment in pigs is a simple, stable and reproducible model to study IRI with minimal systemic effects. MD revealed no signs of anaerobic metabolism in the perfused segment but still there was an increase in the number of polymorphonuclear neutrophils in this segment, although it was lower than that in the ischemic segment.

  • 44. Woods, CM
    et al.
    Sandström, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Bond, M
    Michael, M
    Svanvik, Joar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Toouli, J
    Saccone, GTP
    Selective iNOS inhibition enhances spontaneous gallbladder motility in the Australian possum2007Inngår i: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 19, nr 6, s. 497-503Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Gallbladder inflammation is a common and painful disease. Inducible nitric oxide synthase (iNOS) plays a major role in inflammatory diseases, and iNOS inhibitors are being developed as therapeutic agents. Reports are inconsistent regarding iNOS expression in normal gallbladder. The aim of this study was to determine the effect of iNOS inhibition on spontaneous gallbladder motility. mRNA extracted from normal possum gallbladders was analysed by PCR. Gallbladder contractility was evaluated using a highly selective iNOS inhibitor AR-C102222AA (AR-C) in in vitro muscle strips (0.1-10 000 μm) and in vivo (0.1-30 μmol kg-1) experiments. Gene expression analysis revealed the presence of iNOS mRNA in normal gallbladder (n = 3). In vitro, AR-C (0.1-1000 μmol L-1) produced a concentration-dependent increase in spontaneous gallbladder contractile activity and basal tension (P < 0.05, n = 6). The maximum effect was a 1.8-fold increase in activity and 2.1-fold increase in basal tension. Pretreatment of muscle strips with tetrodotoxin (1 μmol L -1) did not block the AR-C-induced response (n = 5). In vivo, AR-C (30 μmol kg-1, i.v.) increased gallbladder contraction frequency (P < 0.05, n = 8). These data suggest that iNOS is continually expressed in the normal gallbladder, which presumably releases low levels of nitric oxide and in turn may modulate spontaneous gallbladder motility. AR-C may be a beneficial treatment for patients suffering from acute cholecystitis. © 2007 The Authors.

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