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  • 1.
    Ahle, Margareta
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Drott, Peder
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Andersson, Roland
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Epidemiology and Trends of Necrotizing Enterocolitis in Sweden: 1987-20092013In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 132, no 2, p. E443-E451Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate temporal, seasonal, and geographic variations in the incidence of necrotizing enterocolitis (NEC) and its relation to early infant survival in the Swedish population and in subgroups based on gestational age, birth weight, and gender. less thanbrgreater than less thanbrgreater thanMETHODS: In the Swedish birth cohort of 1987 through 2009 all children with a diagnosis of NEC were identified in the National Patient Register, the Swedish Medical Birth Register, and the National Cause of Death Register. NEC incidence, early mortality, and seasonality were analyzed with descriptive statistics, Poisson regression, and auto regression. less thanbrgreater than less thanbrgreater thanRESULTS: The overall incidence of NEC was 3.4 in 10 000 live births, higher in boys than in girls (incidence rate ratio 1.22, 95% confidence interval 1.06-1.40, P = .005), with a peak in November and a trough in May, and increased with an average of similar to 5% a year during the study period. In most subgroups, except the most immature, an initial decrease was followed by a steady increase. Seven-day mortality decreased strongly in all subgroups over the entire study period (annual incidence rate ratio 0.96, 95% confidence interval 0.95-0.96, P andlt; .001). This was especially marked in the most premature and low birth weight infants. less thanbrgreater than less thanbrgreater thanCONCLUSIONS: After an initial decrease, the incidence of NEC has increased in Sweden during the last decades. An association with the concurrent dramatically improved early survival seems likely.

  • 2.
    Al-Ayoubi, Fawzi
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Eriksson, Helene
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Wallon, Conny
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Andersson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Uneven distribution of emergency operations and lack of trauma: a call for reorganization of acute surgical care?2012In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 20Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Subspecialisation within general surgery has today reached further than ever. However, on-call time, an unchanged need for broad surgical skills are required to meet the demands of acute surgical disease and trauma. The introduction of a new subspecialty in North America that deals solely with acute care surgery and trauma is an attempt to offer properly trained surgeons also during on-call time. To find out whether such a subspecialty could be helpful in Sweden we analyzed our workload for emergency surgery and trauma. METHODS: Linkoping University Hospital serves a population of 257 000. Data from 2010 for all patients, diagnoses, times and types of operations, surgeons involved, duration of stay, types of injury and deaths regarding emergency procedures were extracted from a prospectively-collected database and analyzed. RESULTS: There were 2362 admissions, 1559 emergency interventions; 835 were mainly abdominal operations, and 724 diagnostic or therapeutic endoscopies. Of the 1559 emergency interventions, 641 (41.1%) were made outside office hours, and of 453 minor or intermediate procedures (including appendicectomy, cholecystectomy, or proctological procedures) 276 (60.9%) were done during the evenings or at night. Two hundred and fifty-four patients were admitted with trauma and 29 (11.4%) required operation, of whom general surgeons operated on eight (3.1%). Thirteen consultants and 11 senior registrars were involved in 138 bowel resections and 164 cholecystectomies chosen as index operations for standard emergency surgery. The median (range) number of such operations done by each consultant was 6 (3--17) and 6 (1--22). Corresponding figures for senior registrars were 7 (0--11) and 8 (1--39). CONCLUSION: There was an uneven distribution of exposure to acute surgical problems and trauma among general surgeons. Some were exposed to only a few standard emergency interventions and most surgeons did not operate on a single patient with trauma. Further centralization of trauma care, long-term positions at units for emergency surgery and trauma, and subspecialisation in the fields of emergency surgery and trauma, might be options to solve problems of low volumes.

  • 3.
    Altgärde, Jakob
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Redéen, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Hilding, Niclas
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Health Care in Linköping.
    Drott, Peder
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Horse-related trauma in children and adults during a two year period2014In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 22, no 40Article in journal (Refereed)
    Abstract [en]

    Introduction: Horse riding, with almost 200,000 participants, is the eighth most popular sport in Sweden. Severe injuries can occur with horse riding accidents which is well documented. This study was undertaken to investigate if injuries associated with horse riding are common, which type of injuries occur, what mechanisms are involved and to estimate the costs to the society. Material and methods: All patients attending the emergency department at Link ping University Hospital, during the years 2003-2004, due to horse related trauma were prospectively recorded. The patients were divided into two groups according to age, 147 children and 141 adults. The medical records were retrospectively scrutinized. Results: The most common mechanism of injury was falling from the horse. Most commonly, minor sprains and soft tissue injuries were seen, but also minor head injuries and fractures, mainly located in the upper limb. In total 26 adults and 37 children were admitted. Of these 63 patients 19 were considered having a serious injury. In total, four patients needed treatment in intensive care units. The total cost in each group was 200,000 Euro/year. Conclusion: Horse riding is a sport with well known risks. Our results corresponds to the literature, however we have not observed the same incidence of serious injuries. In contrast we find these to be fairly uncommon. The injuries are mainly minor, with a small risk of long term morbidity. Over time regulations and safety equipment seem to have decreased the number of serious accidents.

  • 4.
    Andersson, Peter
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Norblad, Rickard
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Ileorectal anastomosis in comparison with ileal pouch anal anastomosis in reconstructive surgery for ulcerative colitis - a single institution experience2014In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 8, no 7, p. 582-589Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    Ileal pouch anal anastomosis (IPAA) is the standard procedure for reconstruction after colectomy for ulcerative colitis (UC). However, ileorectal anastomosis (IRA) as an alternative has, recently experienced a revival. This study from a single center compares the clinical outcomes of these procedures.

    METHODS:

    From 1992 to 2006, 253 patients consecutively underwent either IRA (n=105) or IPAA (n=148). Selection to either procedure was determined on the basis of rectal inflammation, presence of dysplasia/cancer or patient preferences. Patient-records were retrospectively evaluated. Mean follow-up time was 5.4 and 6.3 years respectively.

    RESULTS:

    Major postoperative complications occurred in 12.4% of patients after IRA and in 12.8% after IPAA (ns). Complications of any kind after IRA or IPAA, even including subsequent stoma-closure, occurred in 23.8% and 39.9% respectively (p<0.01). Estimated cumulative failure rates after 5 and 10 years were 10.1% and 24.1% for IRA and 6.1% and 18.6% for IPAA respectively (ns). The most common cause for failure was intractable proctitis (4.8%) and unspecified dysfunction (4.8%) respectively. At follow-up 76.9% of patients with IRA had proctitis and 34.1% with IPAA had pouchitis. Estimated cumulative cancer-risk after 10, 20 and 25 year duration of disease was 0.0%, 2.1% and 8.7% for IRA. Figures for IPAA were 0.7%, 1.8% and 1.8% (ns).

    CONCLUSION:

    Failure-rates did not significantly differ between patients operated with IRA or IPAA. Patients operated with IPAA had a higher cumulative number of postoperative complications. The high long-term cancer-risk after IRA indicates that this procedure should be an interim solution in younger patients.

  • 5.
    Arnesen, Thomas
    et al.
    Haukeland Hospital, Norway .
    Glomnes, Nina
    University of Bergen, Norway .
    Stromsoy, Siri
    University of Bergen, Norway .
    Knappskog, Stian
    University of Bergen, Norway .
    Heie, Anette
    Haukeland Hospital, Norway .
    Akslen, Lars A.
    University of Bergen, Norway .
    Grytaas, Marianne
    Haukeland Hospital, Norway .
    Varhaug, Jan Erik
    Haukeland Hospital, Norway .
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Brauckhoff, Michael
    Haukeland Hospital, Norway .
    Outcome after surgery for primary hyperaldosteronism may depend on KCNJ5 tumor mutation status: a population-based study from Western Norway2013In: Langenbeck's archives of surgery (Print), ISSN 1435-2443, E-ISSN 1435-2451, Vol. 398, no 6, p. 869-874Article in journal (Refereed)
    Abstract [en]

    Primary aldosteronism (PA) is a frequent cause (about 10 %) of hypertension. Some cases of PA were recently found to be caused by mutations in the potassium channel KCNJ5. Our objective was to determine the mutation status of KCNJ5 and seven additional candidate genes for tumorigenesis: YY1, FZD4, ARHGAP9, ZFP37, KDM5C, LRP1B, and PDE9A and, furthermore, the surgical outcome of PA patients who underwent surgery in Western Norway. less thanbrgreater than less thanbrgreater thanTwenty-eight consecutive patients with aldosterone-producing adrenal tumors (20 patients with single adenoma, 8 patients with unilateral multiple adenomas or hyperplasia) who underwent surgery were included in this study. All patients were operated on by uncomplicated laparoscopic total adrenalectomy. Genomic DNA was isolated from tumor and non-tumor adrenocortical tissue, and DNA sequencing revealed the mutation status. less thanbrgreater than less thanbrgreater thanTen out of 28 (36 %) patients with PA displayed tumor mutations in KCNJ5 (p. G151R and L168R) while none were found in the corresponding non-tumor samples. No mutations were found in the other seven candidate genes screened. The presence of KCNJ5 mutations was associated with lower blood pressure and a higher chance for cure by surgery when compared to patients harboring the KCNJ5 wild type. less thanbrgreater than less thanbrgreater thanKCNJ5 mutations are associated with a better surgical outcome. Preoperative identification of the mutation status might have impact on surgical strategy (total vs. subtotal adrenalectomy).

  • 6.
    Björnsson, Bergthor
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Laparoscopic distal pancreatectomy for adenocarcinoma of the pancreas2014In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 20, no 37, p. 13402-13411Article in journal (Refereed)
    Abstract [en]

    Since the first report on laparoscopic distal pancreatectomy (LDP) appeared in the 1990s, the procedure has been performed increasingly frequently to treat both benign and malignant lesions of the pancreas. Many earlier publications have shown LDP to be a good alternative to open distal pancreatectomy for benign lesions, although this has never been studied in a prospective, randomized manner. The evidence for the use of LDP to treat adenocarcinoma of the pancreas is not as well established. The purpose of this review is to evaluate the current evidence for LDP in cases of pancreatic adenocarcinoma. We conducted a review of English language publications reporting LDP results between 1990 and 2013. All studies reporting results in patients with histologically proven pancreatic adenocarcinoma were included. Thirty-nine publications were found and included in the results for a total of 309 cases of pancreatic adenocarcinoma (potential double publications were not eliminated). Most LDP procedures are performed in selected cases and generally involve smaller tumors than open distal pancreatectomy (ODP) procedures. Some of the papers report unselected cases and include procedures on larger tumors. The number of lymph nodes harvested using LDP is comparable to the number obtained with ODP, as is the frequency of R0 resections. Current data suggest that similar short term oncological results can be obtained using LDP as those obtained using ODP.

  • 7.
    Björnsson, Bergthor
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Winbladh, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Bojmar, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Gullstrand, Per
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Conventional, but not remote ischemic preconditioning, reduces iNOS transcription in liver ischemia/reperfusion2014In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 20, no 28, p. 9506-9512Article in journal (Refereed)
    Abstract [en]

    AIM: To study the effects of preconditioning on inducible nitric oxide synthase (iNOS) and interleukin 1 (IL-1) receptor transcription in rat liver ischemia/reperfusion injury (IRI). METHODS: Seventy-two male rats were randomized into 3 groups: the one-hour segmental ischemia (IRI, n = 24) group, the ischemic preconditioning (IPC, n = 24) group or the remote ischemic preconditioning (R-IPC, n = 24) group. The IPC and R-IPC were performed as 10 min of ischemia and 10 min of reperfusion. The iNOS and the IL-1 receptor mRNA in the liver tissue was analyzed with real time PCR. The total Nitrite and Nitrate (NOx) in continuously sampled microdialysate (MD) from the liver was analyzed. In addition, the NOx levels in the serum were analyzed. RESULTS: After 4 h of reperfusion, the iNOS mRNA was significantly higher in the R-IPC (Delta Ct: 3.44 +/- 0.57) group than in the IPC (Delta Ct: 5.86 +/- 0.82) group (P = 0.025). The IL-1 receptor transcription activity was reduced in the IPC group (Delta Ct: 1.88 +/- 0.53 to 4.81 +/- 0.21), but not in the R-IPC group, during reperfusion (P = 0.027). In the MD, a significant drop in the NOx levels was noted in the R-IPC group (12.3 +/- 2.2 to 4.7 +/- 1.2 mu mol/L) at the end of ischemia compared with the levels in early ischemia (P = 0.008). A similar trend was observed in the IPC group (11.8 +/- 2.1 to 6.4 +/- 1.5 mu mol/L), although this difference was not statistically significant. The levels of NOx rose quickly during reperfusion in both groups. CONCLUSION: IPC, but not R-IPC, reduces iNOS and IL-1 receptor transcription during early reperfusion, indicating a lower inflammatory reaction. NOx is consumed in the ischemic liver lobe.

  • 8.
    Björnsson, Bergthor
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Winbladh, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Bojmar, Linda
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Trulsson, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Gullstrand, Per
    Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Remote or Conventional Ischemic Preconditioning -Local Liver Metabolism in Rats Studied with Microdialysis2012In: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 176, no 1, p. 55-62Article in journal (Refereed)
    Abstract [en]

    Background. Ischemic preconditioning (IPC) of the liver decreases liver injury secondary to ischemia and reperfusion. An attractive alternative to IPC is remote ischemic preconditioning (R-IPC), but these two methods have not previously been compared. Material and Methods. Eighty-seven rats were randomized into four groups: sham operated (n = 15), 1 h segmental ischemia (IRI, n = 24), preceeded by IPC (n = 24), or R-IPC (n = 24) (to the left hindleg). IPC and R-IPC were performed with 10 min ischemia and 10 min of reperfusion. Analyses of liver microdialysate (MD), serum transaminase levels, and liver histology were made. Results. Rats treated with IPC and R-IPC had significantly lower AST, 71.5 (19.6) IU/L respective 96.6 (12.4) at 4 h reperfusion than those subjected to IRI alone, 155 (20.9), P = 0.0004 and P = 0.04 respectively. IPC also had lower ALT levels, 41.6 (11.3) IU/L than had IRI 107.4 (15.5), P = 0.003. The MD glycerol was significantly higher during ischemia in the R-IPC = 759 (84) mu M] and the IRI = 732 (67)] groups than in the IPC 514 (70) group, P = 0.022 and P = 0.046 respectively. The MD glucose after ischemia was lower in the IPC group 7.1 (1.2) than in the IRI group 12.7 (1.6), P = 0.005. Preconditioning to the liver caused an direct increase in lactate, glucose and glycerol in the ischemic segment compared with the control segment an effect not seen in the R-IPC and IRI groups. Conclusions. IPC affects glucose metabolism in the rat liver, observed with MD. IPC reduces liver cell injury during ischemic and reperfusion in rats. R-IPC performed over the same length of time as IPC does not have the same effect as the latter on ALT levels and MD glycerol; this may suggest that R-IPC does not offer the same protection as IPC in this setting of rat liver IRI.

  • 9.
    Bojmar, Linda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Karlsson, Elin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Ellegård, Sander
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Björnsson, Bergthor
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Hallböök, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    The Role of MicroRNA-200 in Progression of Human Colorectal and Breast Cancer2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, p. 84815-Article in journal (Refereed)
    Abstract [en]

    The role of the epithelial-mesenchymal transition (EMT) in cancer has been studied extensively in vitro, but involvement of the EMT in tumorigenesis in vivo is largely unknown. We investigated the potential of microRNAs as clinical markers and analyzed participation of the EMT-associated microRNA-200 ZEB E-cadherin pathway in cancer progression. Expression of the microRNA-200 family was quantified by real-time RT-PCR analysis of fresh-frozen and microdissected formalin-fixed paraffin-embedded primary colorectal tumors, normal colon mucosa, and matched liver metastases. MicroRNA expression was validated by in situ hybridization and after in vitro culture of the malignant cells. To assess EMT as a predictive marker, factors considered relevant in colorectal cancer were investigated in 98 primary breast tumors from a treatment-randomized study. Associations between the studied EMTmarkers were found in primary breast tumors and in colorectal liver metastases. MicroRNA-200 expression in epithelial cells was lower in malignant mucosa than in normal mucosa, and was also decreased in metastatic compared to non-metastatic colorectal cancer. Low microRNA-200 expression in colorectal liver metastases was associated with bad prognosis. In breast cancer, low levels of microRNA-200 were related to reduced survival and high expression of microRNA-200 was predictive of benefit from radiotheraphy. MicroRNA-200 was associated with ER positive status, and inversely correlated to HER2 and overactivation of the PI3K/AKT pathway, that was associated with high ZEB1 mRNA expression. Our findings suggest that the stability of microRNAs makes them suitable as clinical markers and that the EMT-related microRNA-200 - ZEB - E-cadherin signaling pathway is connected to established clinical characteristics and can give useful prognostic and treatment-predictive information in progressive breast and colorectal cancers.

  • 10.
    Bojmar, Linda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Zhang, Haiying
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Costa da Silva, Bruno
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Karlsson, Elin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Vincent, Theresa
    Departments of Physiology and Biophysics and Cell and Developmental Biology, Weill Cornell Medical College, New York, USA / Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Lyden, David
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    miR-18a is regulated between progressive compartments of cancers, and incorporated in exosomes with the potential of creating premetastatic niches and predict cancer outcome2015Manuscript (preprint) (Other academic)
    Abstract [en]

    The ultimate cause of death for many cancer patients is the spread of the cancer via metastasis. Even so, there are still a lack of knowledge regarding the metastasis process. This study was performed to investigate the role of metastamirs in exosomes and their metastatic patterns. We used the well-established isogeneic murine cancer model of low metastatic 67NR cells, mimicking luminal/basal breast tumors, and highly metastatic 4T1 cells with characteristics of basal breast  tumors. We studied the exosomal properties and pre-metastatic effects in this metastasis model and compared human materials and exosomes of several other tumor types. Our data clearly demonstrated that exosomes from the highly metastatic cells home to the metastatic organs of their parental cells whereas exosomes from cells with low metastatic potential mostly located to lymph nodes. The exosome protein cargos also resembled their parental cells and potentially affects their target organs, and cells, differently. Furthermore, the exosomes from the highly metastatic cells had a more pronounced effect on tumor growth and pre-metastatic changes than the low metastatic exosomes. The microRNA-18a, a predictor of metastasis, was present to a higher extent in metastatic exosomes as compared to low metastatic exosomes, and altered the tumor progressive properties. Our findings support the role of exomirs as important players in the metastatic process, the value as biomarkers and potential therapeutic targets.

  • 11.
    Carlsson, Anders H.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Lutgendorff, Femke
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Gastrointestinal Research Unit, Department of Surgery, University Medical Center, Utrecht, The Netherlands.
    Akkermans, Louis M.A.
    Gastrointestinal Research Unit, Department of Surgery, University Medical Center, Utrecht, The Netherlands..
    McKay, Derek M
    Gastrointestinal Research Group, Department of Physiology & Pharmacology, The Calvin, Phoebe and Joan Snyder Institute of Infection, Inflammation and Immunology, University of Calgary, Calgary, Alberta, Canada.
    Söderholm, Johan D.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Probiotics modulate mast cell degranulation and reduce stress-induced barrier dysfunction in vitro2013Manuscript (preprint) (Other academic)
    Abstract [en]

    BACKGROUND: Stress has well-established deleterious effects on intestinal barrier function and stressful life events are known to contribute to the development and perpetuation of inflammatory bowel diseases. Mast cells play a pivotal role in pathogenesis of stressinduced barrier dysfunction due to the release of barrier-disruptive content. Conversely, they also have recently been suggested to contribute to barrier protective properties of probiotics, through the release of 15d-PGJ2 and enhanced epithelial PPAR-γ activity. However, mechanisms remain to be elucidated.

    AIM: To study if probiotics can modulate mast cell mediator release, resulting in amelioration of stress-induced barrier dysfunction in vitro.

    METHODS: Confluent monolayers of the human colon-derived T84 epithelial cell line were co-cultured with rat basophilic leukemia (RBL)-2H3 mast cells and pretreated with probiotics (125x104 CFU/ml, 1hr) before addition of 100nM CRF to activate mast cells. Release of beta hexosaminidase, TNF-α and 15d-PGJ2 from mast cells was determined. Transepithelial resistance (TER), and permeability to microspheres (0.2μm) were measured over a 24h period. To determine dependence of PPAR-γ, monolayers were incubated with the specific PPAR-γ antagonist T0070907 before treatment with probiotics.

    RESULTS: CRF-induced activation of mast cells resulted in decreased TERs and increased permeability to microspheres. Both pretreatment with probiotics and filter-sterilized probiotic supernatant resulted in lower levels of mast cell-released beta hexosaminidase and TNF-α, and increased 15d-PGJ2. Furthermore, probiotics ameliorated epithelial barrier dysfunction in monolayers exposed to CRF-activated mast cells. However, when T84 monolayers were exposed to conditioned medium of CRF-activated mast cells or were incubated with T0070907, probiotics showed little or no effect.

    CONCLUSIONS: Probiotics modulate mast cell mediator release to a more barrier protective profile, resulting in amelioration of stress-induced epithelial barrier dysfunction, which is putatively mediated by a PPAR-γ dependent pathway.

  • 12.
    Carlsson, Anders H.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Yakymenko, Olena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Olivier, Isabelle
    External - unknown .
    Håkansson, Fathima
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Postma, Emily
    External - unknown .
    Keita, Asa V.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Soderholm, Johan D.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Faecalibacterium prausnitzii supernatant improves intestinal barrier function in mice DSS colitis2013In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 48, no 10, p. 1136-1144Article in journal (Refereed)
    Abstract [en]

    Objective. The intestinal microbiota plays a substantial role in the pathogenesis of inflammatory bowel disease (IBD). Faecalibacterium prausnitzii (FP) is underrepresented in IBD patients and have been suggested to have anti-inflammatory effects in mice. Increased intestinal permeability is common in IBD but the relationship between FP and intestinal barrier function has not been investigated. Our aim was to study treatment with FP supernatant on intestinal barrier function in a dextran sodium sulfate (DSS) colitis mice model. Material and methods. C57BL/6 mice received 3% DSS in tap water ad libitum during five days to induce colitis. From day 3 the mice received a daily gavage with FP supernatant or broth during seven days. Ileum and colon were mounted in Ussing chambers for permeability studies with Cr-51-EDTA and Escherichia coli K-12. Colon was saved for Western blot analyses of tight junction proteins. Results. DSS-treated mice showed significant weight loss and colon shortening. Gavage with FP supernatant resulted in a quicker recovery after DSS treatment and less extensive colonic shortening. Ileal mucosa of DSS mice showed a significant increase in Cr-51-EDTA-passage compared to controls. Cr-51-EDTA passage was significantly decreased in mice receiving FP supernatant. No significant differences were observed in passage of E. coli K12. Western blots showed a trend to increased claudin-1 and claudin-2 expressions in DSS mice. Conclusions. Supernatant of FP enhances the intestinal barrier function by affecting paracellular permeability, and may thereby attenuate the severity of DSS-induced colitis in mice. These findings suggest a potential role of FP in the treatment of IBD.

  • 13.
    Collin, A.
    et al.
    Uppsala University, Sweden.
    Jung, Bärbel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Nilsson, E.
    Umeå University, Sweden.
    Pahlman, L.
    Uppsala University, Sweden.
    Folkesson, J.
    Uppsala University, Sweden.
    Impact of mechanical bowel preparation on survival after colonic cancer resection2014In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 101, no 12, p. 1594-+Article in journal (Refereed)
    Abstract [en]

    Background: A randomized study in 1999-2005 of mechanical bowel preparation (MBP) preceding colonic resection found no decrease in postoperative complications. The aim of the present study was to evaluate the long-term effect of MBP regarding cancer recurrence and survival after colonic resections. Methods: The cohort of patients with colonic cancer in the MBP study was followed up for 10 years. Data were collected from registers run by the National Board of Health and Welfare. Register data were validated against information in patient charts. Cox proportional hazards model was used for multivariable analysis of factors predictive of cancer-specific survival. Results: Register analysis showed significantly fewer recurrences, and better cancer-specific and overall survival in the MBP group. After validation, 839 of 1343 patients remained for analysis (448 MBP, 391 no MBP). Eighty (17.9 per cent) of 448 patients in the MBP group and 88 (22.5 per cent) of 391 in the no-MBP group developed a cancer recurrence (P = 0.093). The 10-year cancer-specific survival rate was 84.1 per cent in the MBP group and 78.0 per cent in the no-MBP group (P = 0.019). Overall survival rates were 58.8 and 56.0 per cent respectively (P = 0.186). Conclusion: Patients receiving MBP before elective colonic cancer surgery had significantly better cancer-specific survival after 10 years.

  • 14.
    Crafoord, Kristina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Brynhildsen, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Hallböök, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Pelvic organ prolapse and anorectal manometry: a prospective study2012In: Urogynaecologia International Journal, ISSN 1121-3086, E-ISSN 2038-8314, Vol. 26, no 1, p. 12-16Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate associations between anal sphincter pressure and stage of prolapse and bowel and prolapse symptoms among women undergoing prolapse surgery and to determine whether anal sphincter pressure could predict symptomatic and anatomical outcomes of prolapse surgery. Fortytwo women with pelvic organ prolapse (POP) stage 2-3 were included in this prospective longitudinal study. Pre- and postoperative evaluation by means of a symptom questionnaire, clinical examination and anorectal manometry. The vaginal prolapse surgery included at the very least posterior colporrhaphy. Analysis of variance and covariance and logistic regression models were used for statistical analyses. The anal sphincter pressure at rest and squeeze was significantly lower in women with the symptom vaginal protrusion than in the women without the symptom. No associations were found between anal sphincter pressure and the extent or degree of prolapse or subjective and anatomical outcomes of POP surgery. The prolapse symptom vaginal protrusion is associated with a low anal sphincter pressure but the anal sphincter pressure does not seem to predict the outcome of POP surgery, neither regarding symptoms nor anatomy.

  • 15.
    Dutta, Ravi Kumar
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Brauckhoff, Michael
    Haukeland University Hospital, Bergen; University of Bergen, Norway .
    Walz, Martin
    Klinikum Essen Mitte, Essen, Germany .
    Alesina, Piero
    Klinikum Essen Mitte, Essen, Germany .
    Arnesen, Thomas
    Haukeland University Hospital, Bergen; University of Bergen, Norway.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Complementary somatic mutations of KCNJ5, ATP1A1, and ATP2B3 in sporadic aldosterone producing adrenal adenomas2014In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 21, no 1, p. L1-L4Article in journal (Other academic)
    Abstract [en]

    n/a

  • 16.
    Eriksson, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Jacobs, Claudia
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Johansson, Karl-Erik
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL.
    Remission of arthritis after esophagectomy in three patients with severe achalasia2013In: Diseases of the esophagus, ISSN 1120-8694, E-ISSN 1442-2050, Vol. 26, no 3, p. 226-230Article in journal (Refereed)
    Abstract [en]

    In the 1960s and 1970s, intestinal bypass surgery was performed to treat patients with extreme obesity. However, this is now done with great restriction due to the risk of complications, for instance, polyarthritis. An association between severe achalasia and arthritis has also been described, but very few articles on this topic are cited in PubMed, and most of the published case reports are old. In this article, we present a retrospective case series of three patients with severe achalasia and arthritis from the departments of rheumatology and surgery at a university hospital. The complaints from the esophagus as well as arthritis were resolved after esophagectomy and esophageal reconstruction. We conclude that severe achalasia can be associated with arthritis, and both can be cured by esophageal reconstruction. Thus, we want to remind of this rare, but probably largely unrecognized, association between achalasia and joint disease.

  • 17.
    Floodeen, H
    et al.
    Örebro University Hospital, Sweden .
    Hallböök, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Rutegard, J
    Umeå University Hospital, Sweden .
    Sjödahl, Rune
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Matthiessen, P
    Örebro University Hospital, Sweden .
    Early and late symptomatic anastomotic leakage following low anterior resection of the rectum for cancer: are they different entities?2013In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 15, no 3, p. 334-340Article in journal (Refereed)
    Abstract [en]

    Aim The aim of the study was to compare patients with symptomatic anastomotic leakage following low anterior resection of the rectum (LAR) for cancer diagnosed during the initial hospital stay with those in whom leakage was diagnosed after hospital discharge. Method Forty-five patients undergoing LAR (n=234) entered into a randomized multicentre trial (NCT 00636948), who developed symptomatic anastomotic leakage, were identified. A comparison was made between patients diagnosed during the initial hospital stay on median postoperative day 8 (early leakage, EL; n=27) and patients diagnosed after hospital discharge at median postoperative day 22 (late leakage, LL; n=18). Patient characteristics, operative details, postoperative course and anatomical localization of the leakage were analysed. Results Leakage from the circular stapler line of an end-to-end anastomosis was more common in EL, while leakage from the stapler line of the efferent limb of the J-pouch or side-to-end anastomosis tended to be more frequent in LL (P=0.057). Intra-operative blood loss (P=0.006) and operation time (P=0.071) were increased in EL compared with LL. On postoperative day 5, EL performed worse than LL with regard to temperature (P=0.021), oral intake (P=0.006) and recovery of bowel activity (P=0.054). Anastomotic leakage was diagnosed most often by a rectal contrast study in EL and by CT scan in LL. The median initial hospital stay was 28days for EL and 10days for LL (Pandlt;0.001). Conclusion The present study has demonstrated that symptomatic anastomotic leakage can present before and after hospital discharge and raises the question of whether early and late leakage after LAR may be different entities.

  • 18.
    Floodeen, Hannah
    et al.
    Örebro University Hospital, Sweden.
    Lindgren, Rickard
    Örebro University Hospital, Sweden.
    Hallböök, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Matthiessen, Peter
    Örebro University Hospital, Sweden; University of Örebro, Sweden .
    Evaluation of Long-term Anorectal Function After Low Anterior Resection: A 5-Year Follow-up of a Randomized Multicenter Trial2014In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 57, no 10, p. 1162-1168Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Anorectal function after rectal surgery with low anastomosis is often impaired. Outcome of long-term anorectal function is poorly understood but may improve over time. OBJECTIVE: We evaluated anorectal function 5 years after low anterior resection for cancer with regard to whether patients had a temporary stoma at initial resection. The objective of this study was to assess changes in anorectal function over time by comparing the results with anorectal function 1 year after rectal resection. DESIGN: This study was a secondary end point of a randomized, multicenter controlled trial. SETTINGS: The study was conducted at 21 Swedish hospitals performing rectal cancer surgery from 1999 to 2005. PATIENTS: Patients included were those operated on with low anterior resection. INTERVENTIONS: Patients were randomly assigned to receive or not receive a defunctioning stoma. MAIN OUTCOME MEASURES: We evaluated anorectal function in patients who were initially randomly assigned to the defunctioning stoma or no stoma group, who had been free of stoma for 5 years, by means of using a standardized patient questionnaire. Questions addressed stool frequency, urgency, fragmentation of bowel movements, evacuation difficulties, incontinence, lifestyle alterations, and patient preference regarding permanent stoma formation. Results were compared with the same patient cohort at 1-year follow-up. RESULTS: A total of 123 patients answered the bowel function questionnaire (65 in the no-stoma group and 58 in the stoma group). No differences were found between groups regarding the number of passed stools, need for medication to open the bowel, evacuation difficulties, incontinence, and urgency. General well-being was significantly better in the no-stoma group (p = 0.033). Comparison with anorectal function at 1 year showed no further changes over time. LIMITATIONS: The study was based on a limited sample size (n = 123) and formed a secondary end point of a randomized trial. CONCLUSIONS: Anorectal function was impaired for many patients, but the temporary presence of a defunctioning stoma after rectal resection did not affect long-term outcome. Anorectal function did not change between 1-year and 5-year follow-up.

  • 19.
    Gerjy, Roger
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Derwinger, K.
    Sahlgrenska University Hospital, Göteborg.
    Lindhoff-Larsson, Anna
    Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL.
    Nyström, P-O
    Karolinska Institutet, Stockholm.
    Long-term results of stapled haemorrhoidopexy in a prospective single centre study of 153 patients with 1-6 years follow-up2012In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 14, no 4, p. 490-496Article in journal (Refereed)
    Abstract [en]

    Aim The long-term results of stapled haemorrhoidopexy for prolapsed haemorrhoids were assessed using uniform methods to acquire data and pre-set definitions of failure, recurrence, residual symptoms and impaired continence. less thanbrgreater than less thanbrgreater thanMethod From October 1999 to May 2005, 153 patients underwent a stapled haemorrhoidopexy and were enrolled prospectively. They were assessed preoperatively, postoperatively and at the end of the study from replies to a questionnaire about symptoms and continence. Preoperatively, manual reduction of prolapse was required in 103 patients, skin tags were found in 115 patients (circumferential in 22) and impaired continence in 63. less thanbrgreater than less thanbrgreater thanResults In all, 145 patients completed preoperative and long-term protocols and were analysed as paired data, at a mean follow-up of 32 months. Failure to control the prolapse or recurrence was seen in 19 (13%) patients including nine reoperations for prolapse. Symptoms improved from 8.1 to 2.5 points on a 15-point scale (P = 0.001). Symptoms were not controlled in 25 (17%) patients. Continence improved from 4.7 to 2.9 points on a 15-point scale (P = 0.001). Twenty-five (17%) patients still had a continence disturbance. Altogether 51 (35%) patients had a deficient outcome with respect to prolapse, symptoms or continence. There were no major adverse events. less thanbrgreater than less thanbrgreater thanConclusion Restoration of the anal anatomy by stapled haemorrhoidopexy resulted in a significant improvement in haemorrhoid-associated symptoms and continence but a third of patients had poor symptom control including 13% with persisting prolapse.

  • 20.
    Gimm, Oliver
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Arnesson, Lars-Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL.
    Olofsson, Pia
    Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL. Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Morales, Olallo
    Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL.
    Juhlin, Claes
    Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL. Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Super-selective venous sampling in conjunction with quickPTH for patients with persistent primary hyperparathyroidism: report of five cases2012In: Surgery today (Print), ISSN 0941-1291, E-ISSN 1436-2813, Vol. 42, no 6, p. 570-576Article in journal (Refereed)
    Abstract [en]

    Selective venous sampling (SVS) helps to interpret imaging results in patients with persistent primary hyperparathyroidism (pHPT). However, one of the drawbacks of conventional SVS may be low "spatial resolution", depending on the sample size. We modified SVS in the following way: first, patients underwent conventional SVS with up to 11 parathyroid hormone (PTH) samples taken. The quickPTH assay was used to measure PTH levels. The patients subsequently underwent super-selective venous sampling (super-SVS) in the region with the highest quickPTH level in the same session. The subjects were five consecutive patients with persistent pHPT investigated by various imaging techniques, none of which was considered conclusive. Therefore, all five patients underwent super-SVS, which was done successfully in four. Re-evaluation of the imaging results of these four patients resulted in localization of the parathyroid adenoma. Curative surgery was performed successfully in all four patients during the study period. Super-SVS increases the "spatial resolution" of conventional SVS and may have advantages when imaging results of patients with persistent pHPT are interpreted. Its true value must be analyzed in larger studies.

  • 21.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Behm, Pascal
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology. University of Applied Sciences in Northwest Switzerland.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fluorescence spectroscopy using indocyanine green for lymph node mapping2014Conference paper (Refereed)
    Abstract [en]

    The principles of cancer treatment has for years been radical resection of the primary tumor. In the oncologic surgeries where the affected cancer site is close to the lymphatic system, it is as important to detect the draining lymph nodes for metastasis (lymph node mapping). As a replacement for conventional radioactive labeling, indocyanine green (ICG) has shown successful results in lymph node mapping; however, most of the ICG fluorescence detection techniques developed are based on camera imaging. In this work, fluorescence spectroscopy using a fiber-optical probe was evaluated on a tissue-like ICG phantom with ICG concentrations of 6-64 μM and on breast tissue from five patients. Fiber-optical based spectroscopy was able to detect ICG fluorescence at low intensities; therefore, it is expected to increase the detection threshold of the conventional imaging systems when used intraoperatively. The probe allows spectral characterization of the fluorescence and navigation in the tissue as opposed to camera imaging which is limited to the view on the surface of the tissue

  • 22.
    Holmberg, L
    et al.
    Kings Coll London, England .
    Wong, Y N S
    Kings Coll London, England .
    Tabar, L
    Uppsala University, Sweden .
    Ringberg, A
    University Hospital MAS, Sweden .
    Karlsson, P
    Sahlgrens University Hospital, Sweden .
    Arnesson, Lars-Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Sandelin, K
    Karolinska University Hospital, Sweden .
    Anderson, H
    Lund University, Sweden .
    Garmo, H
    Kings Coll London, England .
    Emdin, S
    Umeå University Hospital, Sweden .
    Mammography casting-type calcification and risk of local recurrence in DCIS: analyses from a randomised study2013In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 108, no 4, p. 812-819Article in journal (Refereed)
    Abstract [en]

    Background: We studied the association between mammographic calcifications and local recurrence in the ipsilateral breast. less thanbrgreater than less thanbrgreater thanMethods: Case-cohort study within a randomised trial of radiotherapy in breast conservation for ductal cancer in situ of the breast (SweDCIS). We studied mammograms from cases with an ipsilateral breast event (IBE) and from a subcohort randomly sampled at baseline. Lesions were classified as a density without calcifications, architectural distortion, powdery, crushed stone-like or casting-type calcifications. less thanbrgreater than less thanbrgreater thanResults: Calcifications representing necrosis were found predominantly in younger women. Women with crushed stone or casting-type microcalcifications had higher histopathological grade and more extensive disease. The relative risk (RR) of a new IBE comparing those with casting-type calcifications to those without calcifications was 2.10 (95% confidence interval (Cl) 0.92-4.80). This risk was confined to in situ recurrences; the RR of an IBE associated with casting-type calcifications on the mammogram adjusted for age and disease extent was 16.4 (95% Cl 2.20-140). less thanbrgreater than less thanbrgreater thanConclusion: Mammographic appearance of ductal carcinoma in situ of the breast is prognostic for the risk of an in situ IBE and may also be an indicator of responsiveness to RT in younger women.

  • 23.
    Johansson, E
    et al.
    Östergötlands Läns Landsting.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Ingemansson, A
    Östergötlands Läns Landsting.
    Ryn, A-K
    Hallbook, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL.
    Randomized trial of biofeedback or medical treatment for fecal incontinence in NEUROGASTROENTEROLOGY AND MOTILITY, vol 24, issue , pp 183-1832012In: NEUROGASTROENTEROLOGY AND MOTILITY, Blackwell Publishing , 2012, Vol. 24, p. 183-183Conference paper (Refereed)
    Abstract [en]

    n/a

  • 24.
    Karlsson, Anneli
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Ryberg, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Dehnoei, Marjan Nosouhi
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Borch, Kurt
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL.
    Monstein, Hans-Jürg
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Association between cagA and vacA genotypes and pathogenesis in a Helicobacter pylori infected population from South-eastern Sweden2012In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 12, no 129Article in journal (Refereed)
    Abstract [en]

    UNLABELLED: ABSTRACT:

    BACKGROUND: Chronic gastritis, peptic ulcer disease, and gastric cancer have been shown to be related to infection with Helicobacter pylori (H. pylori). Two major virulence factors of H. pylori, CagA and VacA, have been associated with these sequelae of the infection. In this study, total DNA was isolated from gastric biopsy specimens to assess the cagA and vacA genotypes.

    RESULTS: Variations in H. pylori cagA EPIYA motifs and the mosaic structure of vacA s/m/i/d regions were analysed in 155 H. pylori-positive gastric biopsies from 71 individuals using PCR and sequencing. Analysis of a possible association between cagA and vacA genotypes and gastroduodenal pathogenesis was made by logistic regression analysis. We found that H. pylori strains with variation in the number of cagA EPIYA motif variants present in the same biopsy correlated with peptic ulcer, while occurrence of two or more EPIYA-C motifs was associated with atrophy in the gastric mucosa. No statistically significant relation between vacA genotypes and gastroduodenal pathogenesis was observed.

    CONCLUSIONS: The results of this study indicate that cagA genotypes may be important determinants in the development of gastroduodenal sequelae of H. pylori infection. In contrast to other studies, vacA genotypes were not related to disease progression or outcome. In order to fully understand the relations between cagA, vacA and gastroduodenal pathogenesis, the mechanisms by which CagA and VacA act and interact need to be further investigated.

  • 25.
    Keita, Åsa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Carlsson, A H.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Cigehn, M
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ericson, Ann-Charlott
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Mckay, D M:
    University of Calgary, Canada .
    Söderholm, Johan D.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Vasoactive intestinal polypeptide regulates barrier function via mast cells in human intestinal follicle-associated epithelium and during stress in rats2013In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 25, no 6, p. e406-e417Article in journal (Refereed)
    Abstract [en]

    Background Vasoactive intestinal polypeptide (VIP) has been implicated as a regulator of intestinal barrier function and inflammation. Our aim was to elucidate the role of VIP in follicle-associated epithelium (FAE) and villus epithelium (VE) permeability following stress in rats and on human intestinal barrier function. Methods Rats were injected intraperitoneally (i.p.) with VIP receptor-antagonists (anti-VPACs), a mast cell stabilizer, doxantrazole (DOX), or NaCl, and submitted to acute water avoidance stress. Ileal segments were mounted in Ussing chambers to assess 51chromium-edta (51Cr-edta) and Escherichia (E.) coli (strain K-12) permeability. Rat ileal and human ileal and colonic segments were exposed to VIP +/- anti-VPACs or DOX. An in vitro co-culture model of human FAE was used to study epithelial-VIP effects. VIP/VPACs distribution was assessed by microscopy. Key Results Stress increased 51Cr-edta and E.coli permeability in VE and FAE. The increases were abolished by i.p. injection of DOX or anti-VPACs. Ileal VIP-exposure ex vivo increased bacterial passage and this was reduced by DOX. In human FAE ex vivo, VIP treatment doubled bacterial uptake, which was normalized by DOX or anti-VPACs. No barrier effects were observed in human colonic tissue. VPACs were found in rat and human ileal follicles, with partial mast cell co-localization. The co-culture model confirmed VIPmast cellepithelial interactions in the regulation of barrier function. Conclusions andamp; Inferences Stress affects the FAE barrier by mechanisms involving VIP and VPACs on mucosal mast cells. We suggest a regulatory role for VIP in the control of ileal permeability that may be relevant to bacterialepithelial interactions in stress-related intestinal disorders.

  • 26.
    Keita, Åsa V.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Söderholm, Johan D.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL.
    Barrier dysfunction and bacterial uptake in the follicle-associated epithelium of ileal Crohns disease2012In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1258, no 1, p. 125-134Article in journal (Refereed)
    Abstract [en]

    The ability to control uptake across the mucosa and protect from harmful substances in the gut lumen is defined as intestinal barrier function. The etiology of Crohns disease is unknown, but genetic, environmental, and immunological factors all contribute. The frontline between these factors lies in the intestinal barrier. The most important inflammation-driving environmental factor in Crohns disease is the microbiota, where Esherichia coli strains have been assigned a key role. The first observable signs of Crohns disease are small aphtoid ulcers over Peyers patches and lymphoid follicles. The overlaying follicle-associated epithelium (FAE) is specialized for luminal sampling and is an entry site for antigens and bacteria. We have demonstrated increased E. coli uptake across the FAE in Crohns disease, which may initiate inflammation. This short review will discuss barrier dysfunction and bacteria in the context of ileal Crohns disease, and how the FAE might be the site of initial inflammation.

  • 27.
    Kugelberg, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Schiavi, Francesca
    Veneto Institute Oncology IRCCS, Italy .
    Fassina, Ambrogio
    University of Padua, Italy .
    Backdahl, Martin
    Karolinska Institute, Sweden .
    Larsson, Catharina
    Karolinska Institute, Sweden .
    Opocher, Giuseppe
    Veneto Institute Oncology IRCCS, Italy University of Padua, Italy .
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Dahia, Patricia L.
    University of Texas Health Science Centre San Antonio, TX 78229 USA .
    Neumann, Hartmut P. H.
    University of Freiburg, Germany .
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Role of SDHAF2 and SDHD in von Hippel-Lindau Associated Pheochromocytomas2014In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 38, no 3, p. 724-732Article in journal (Refereed)
    Abstract [en]

    Background Pheochromocytomas (PCCs) develop from the adrenal medulla and are often part of a hereditary syndrome such as von Hippel-Lindau (VHL) syndrome. In VHL, only about 30 % of patients with a VHL missense mutation develop PCCs. Thus, additional genetic events leading to formation of such tumors in patients with VHL syndrome are sought. SDHAF2 (previously termed SDH5) and SDHD are both located on chromosome 11q and are required for the function of mitochondrial complex II. While SDHAF2 has been shown to be mutated in patients with paragangliomas (PGLs), SDHD mutations have been found both in patients with PCCs and in patients with PGLs. Materials and methods Because loss of 11q is a common event in VHL-associated PCCs, we aimed to investigate whether SDHAF2 and SDHD are targets. In the present study, 41 VHL-associated PCCs were screened for mutations and loss of heterozygosity (LOH) in SDHAF2 or SDHD. Promoter methylation, as well as mRNA expression of SDHAF2 and SDHD, was studied. In addition, immunohistochemistry (IHC) of SDHB, known to be a universal marker for loss of any part the SDH complex, was conducted. Results and conclusions LOH was found in more than 50 % of the VHL-associated PCCs, and was correlated with a significant decrease (p less than 0.05) in both SDHAF2 and SDHD mRNA expression, which may be suggestive of a pathogenic role. However, while SDHB protein expression as determined by IHC in a small cohort of tumors was lower in PCCs than in the surrounding adrenal cortex, there was no obvious correlation with LOH or the level of SDHAF2/SDHD mRNA expression. In addition, the lack of mutations and promoter methylation in the investigated samples indicates that other events on chromosome 11 might be involved in the development of PCCs in association with VHL syndrome.

  • 28.
    Kuninty, Praneeth R.
    et al.
    Department of Biomaterials, Science and Technology, Section: Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, The Netherlands.
    Bojmar, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Tjomsland, Vegard
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Hepato-pancreato-biliary Surgery, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Storm, Gert
    Department of Biomaterials, Science and Technology, Section: Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, The Netherlands / Department of Pharmaceutics, Utrecht University, The Netherlands.
    Östman, Arne
    Department of Oncology-Pathology, Cancer Centre Karolinska, Karolinska Institutet, Sweden.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Prakash, Jai
    Department of Biomaterials, Science and Technology, Section: Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, The Netherlands / Department of Oncology-Pathology, Cancer Centre Karolinska, Karolinska Institutet, Sweden.
    MicroRNA-199a and -214 as potential therapeutic targets in pancreatic stellate cells in pancreatic tumor2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 13, p. 16396-16408Article in journal (Refereed)
    Abstract [en]

    Pancreatic stellate cells (PSCs) are the key precursor cells for cancer-associated fibroblasts (CAFs) in pancreatic tumor stroma. Although depletion of tumor stroma is debatable, attenuation of PSC activity is still an interesting strategy to treat pancreatic cancer. In this study, we explored miRNA as therapeutic targets in tumor stroma and found miR-199a-3p and miR-214-3p induced in patient-derived pancreatic CAFs as well as in TGF-β-activated human PSCs (hPSCs). Inhibition of miR-199a or miR-214 using their hairpin inhibitors in hPSCs significantly inhibited their TGFβ-induced differentiation (gene and protein levels of α-SMA, Collagen, PDGFβR), migration and proliferation. Furthermore, heterospheroids of Panc-1 and hPSCs were prepared, which attained smaller size when hPSCs were transfected with anti-miR-199a or -214 than those transfected with control anti-miR. The conditioned medium obtained from TGFβ-activated hPSCs induced tumor cell proliferation and endothelial cell tube formation, but these effects were abrogated when hPSCs were transfected with anti-miR-199a or miR-214. Moreover, IPA analyses revealed signaling pathways related to miR-199a (TP53, mTOR, Smad1) and miR-214 (PTEN, Bax, ING4). Taken together, this study reveals miR-199a-3p and miR-214-3p as major regulators of PSC activation and PSC-induced pro-tumoral effects, representing them as key therapeutic targets in PSCs in pancreatic cancer.

  • 29.
    Linderholm, B K.
    et al.
    Sahlgrens Acad, Sweden .
    Linder, S
    Karolinska Institute, Sweden .
    Arnesson, Lars-Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Identification of intermediate risk breast cancer patients with1-3 positive lymph nodes and excellent survival after tamoxifen as only systemic adjuvant therapy by use of markers of proliferation and apoptosis2013In: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 22, no 5, p. 643-649Article in journal (Refereed)
    Abstract [en]

    Background: According to current guidelines, patients with primary breast cancer and 1-3 lymph node metastases will in general be offered adjuvant chemotherapy. less thanbrgreater than less thanbrgreater thanAim: Our objective was to investigate the relationship between markers of proliferation and apoptosis with survival for patients subjected to adjuvant tamoxifen solely. less thanbrgreater than less thanbrgreater thanMaterial and methods: Tumour cytosol samples from 409 consecutive patients with operable oestrogen receptor positive BC, stage I-III and treated with tamoxifen for 2 or 5 years were assessed for levels of caspase-cleaved cytokeratin-18 (ccCK18), an indicator of apoptosis, by use of an ELISA assay. Data on S-phase fraction (SPF) were available for 370 patients. Survival analyses were performed according to levels of ccCK18 and SPF separately, as well as combined. less thanbrgreater than less thanbrgreater thanResults: A wide range of ccCK18 protein levels was found, median 9.97, range 0.0-87.3 pg/mu gDNA. Increasing SPFs were significantly associated with a lower distant recurrence-free survival (DRFS) (p = 0.025) and breast cancer survival (BCS) (p = 0.046). In the group with low SPF (below mean), low amounts of ccCK/18 correlated with a shorter DRFS (p = 0.0028) and BCS (p = 0.0027). A Proliferation Index (PI); a quotient of ccCK18/SPF was constructed. Low PI (high ccCK18/SPF ratios) were significantly correlated with an improved survival both when analysed as continuous variables; DRFS (p = 0.021), BCS (p = 0.038) and when divided into quartiles; DRFS (p andlt; 0.001) and BCS (p = 0.0012). A similar correlation was found in patients with 1-3 lymph node metastases; DRFS (p = 0.089) and BCS (p = 0.019). A Coxs proportional hazard model including age, tumour size, lymph node status, PgR and ccCK18/SPF was used for multivariate analysis. High ccCK18/SPF ratios correlated with improved survival; DRFS (HR = 0.47 (0.22-0.98), p = 0.043), and BCS (HR = 0.39 (0.16-1.00), p = 0.049), respectively. less thanbrgreater than less thanbrgreater thanConclusion: By use of a proliferation index based on markers of proliferation and apoptosis, a group of patients with 1-3 lymph node metastases with good outcome following adjuvant tamoxifen was identified; this group could possibly be spared adjuvant chemotherapy.

  • 30.
    Lundgren, Charlotte
    et al.
    Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Culture and Communication, Language and Culture. Linköping University, Department of Culture and Communication, Swedish Studies and Comparative Literature.
    Lagerfelt, Marie
    Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL.
    Kommunikation och lärande i multidisciplinärt samarbete: exemplet CUUS2012Conference paper (Other academic)
  • 31.
    Lutgendorff, Femke
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Gastrointestinal Research Unit, Department of Surgery, University Medical Center, Utrecht, The Netherlands.
    Carlsson, Anders H.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Timmerman, Harro M.
    Gastrointestinal Research Unit, Department of Surgery, University Medical Center, Utrecht, The Netherlands.
    Akkermans, Louis M.A.
    Gastrointestinal Research Unit, Department of Surgery, University Medical Center, Utrecht, The Netherlands..
    Söderholm, Johan D.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Protective Effects of Probiotics on Chronic Stress-Induced Intestinal Permeability in Rats are mediated via Mast Cells and PPARγ2013Manuscript (preprint) (Other academic)
    Abstract [en]

    BACKGROUND: Chronic stress, which may affect in the clinical course of inflammatory and functional bowel diseases, disrupts intestinal barrier function by routes involving mast cells. Probiotics have been shown to ameliorate the deleterious effects of stress on intestinal function, but mechanisms remain to be elucidated. Peroxisome proliferator-activated receptor (PPAR)-γ signaling is activated as an endogenous defense mechanism during chronic stress and evidence suggests that probiotics reduce the degradation of PPAR-γ. As a source of the endogenous agonist for PPAR-γ, 15d-PGJ2, and as an important mediator of the stress response, mast cells may have both a beneficial and a deleterious role in the effects on intestinal function by probiotics.

    AIM: Our aim was to study if mast cells contribute to the positive effects of probiotic therapy on intestinal function in a rat model of chronic stress.

    METHODS: 32 Mast cell deficient (Ws/Ws) and 32 wild-type (+/+) rats were subjected to water avoidance stress (WAS) or sham stress (SS) 1hr/day for 10 days. Seven days prior to the onset of stress, probiotics (PB, multispecies combination of 10 different lactic acid bacteria) were added to the standard diet (St) in half of the animals. To determine dependence of PPAR-γ, 8 probiotic-fed wild-type rats subjected to WAS were injected daily with the specific PPAR-γ antagonist T0070907. The colonic mucosa was exposed to E. coli HB101 incorporated with green fluorescent protein and permeability was assessed in Ussing chambers. Mesenteric lymph nodes (MLN) were cultured to determine bacterial translocation.

    RESULTS: Chronic stress induced a marked increase in ileal permeability to E.coli HB101 in +/+ rats (0.17±0.1 x106CFU/hr in SS/St/++ vs. 2.13±0.4 in WAS/St/++; P<0.001). This breach in barrier integrity was less pronounced in Ws/Ws rats (2.13±0.4 in WAS/St/++ vs. 1.19±0.3 in WAS/St/WsWs; P<0.01). Probiotics prevented stress-induced effects in E.coli HB101 passage only in wild-type rats (82% decrease in +/+ vs. 0% in Ws/Ws rats). Furthermore, only in the presence of mast cells did probiotics reduce the enhanced bacterial translocation to MLNs during chronic stress. In wild-type rats treated with a PPAR-γ antagonist, the barrier protective effects of probiotics were diminished.

    CONCLUSIONS: Mast cells acting via a PPAR-γ dependent pathway contribute to the beneficial effects of probiotics on chronic stress-induced mucosal dysfunction in rats.

  • 32.
    Myrelid, Pär
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Druvefors, Pelle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Andersson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Recurrent volvulus of an ileal pouch requiring repeat pouchopexy: a lesson learnt.2014In: Case Reports in Surgery, ISSN 2090-6919, E-ISSN 2090-6900, Vol. 2014, p. 807640-Article in journal (Refereed)
    Abstract [en]

    Introduction. Restorative surgery for ulcerative colitis with ileal pouch anal anastomosis (IPAA) is frequently accompanied by complications. Volvulus of the ileal pouch is one of the most rarely reported late complications and to our knowledge no report exists on reoperative surgery for this condition. Case Report. A 58-year-old woman who previously had undergone restorative proctocolectomy due to ulcerative colitis with an IPAA presented with volvulus of the pouch. She was operated with a single row pouchopexy to the presacral fascia. Two months later she returned with a recurrent volvulus. At reoperation, the pouch was found to have become completely detached from the fascia. A new pexy was made by firmly anchoring the pouch with two rows of sutures to the presacral fascia as well as with sutures to the lateral pelvic walls. At follow-up after five months she was free of symptoms. Conclusion. This first report ever on reoperative surgery for volvulus of a pelvic pouch indicates that a single row pouchopexy might be insufficient for preventing retwisting. Several rows seem to be needed.

  • 33.
    Myrelid, Pär
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Oxford University Hospital, England .
    Marti-Gallostra, M.
    Oxford University Hospital, England University Hospital Valle de Hebron, Spain .
    Ashraf, S.
    Oxford University Hospital, England .
    Sunde, M.L.
    University of Oslo, Norway Akershus University Hospital, Norway .
    Tholin, M.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Oresland, T.
    University of Oslo, Norway Akershus University Hospital, Norway .
    Lovegrove, R.E.
    Oxford University Hospital, England .
    Tottrup, A.
    Aarhus University Hospital, Denmark .
    Kjaer, D.W.
    Aarhus University Hospital, Denmark .
    George, B.D.
    Oxford University Hospital, England .
    Complications in surgery for Crohns disease after preoperative antitumour necrosis factor therapy2014In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 101, no 5, p. 539-545Article in journal (Refereed)
    Abstract [en]

    Background: The use of biological therapy (biologicals) is established in the treatment of Crohns disease. This study aimed to determine whether preoperative treatment with biologicals is associated with an increased rate of complications following surgery for Crohns disease with intestinal anastomosis. Methods: All patients receiving biologicals and undergoing abdominal surgery with anastomosis or strictureplasty were identified at six tertiary referral centres. Demographic data, and preoperative, operative and postoperative details were registered. Patients who were treated with biologicals within 2 months before surgery were compared with a control group who were not. Postoperative complications were classified according to anastomotic, infectious or other complications, and graded according to the Clavien-Dindo classification. Results: Some 111 patients treated with biologicals within 2 months before surgery were compared with 187 patients in the control group. The groups were well matched. There were no differences between the treatment and control groups in the rate of complications of any type (34.2 versus 28.9 per cent respectively; P = 0.402), anastomotic complications (7.2 versus 8.0 per cent; P = 0.976) and non-anastomotic infectious complications (16.2 versus 13.9 per cent; P = 0.586). In univariable regression analysis, biologicals were not associated with an increased risk of any complication (odds ratio (OR) 1.33, 95 per cent confidence interval 0.81 to 2.20), anastomotic complication (OR 0.89, 0.37 to 2.17) or infectious complication (OR 1.09, 0.62 to 1.91). Conclusion: Treatment with biologicals within 2 months of surgery for Crohns disease with intestinal anastomosis was not associated with an increased risk of complications.

  • 34.
    Nilsson, Andreas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Grossmann, Benjamin
    Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Kullman, Eric
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Uustal, Eva
    Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Nilsson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Sedation during endoscopic retrograde cholangiopancreatography: A randomised controlled study of patient-controlled propofol sedation and that given by a nurse anaesthetist2015In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 50, no 10, p. 1285-1292Article in journal (Refereed)
    Abstract [en]

    Objective: Different regimens are used for sedation during ERCP (endoscopic retrograde cholangiopancreatography). Our objectives were to compare safety, ease of treatment, time to recovery and patients’ experiences using PCS (patient-controlled sedation) with propofol as well as sedation given by a nurse anaesthetist (ACS) with propofol or midazolam during ERCP.

    Material and methods: The study included 281 adults in 301 procedures. The PCS group (n=101) delivered bolus doses of 5 mg of propofol according to their need for sedation. The ACS group (n=100) had 2-8 mg/kg/hour of propofol infused, with the target for sedation being Level 3 of the Observer’s Assessment of Alertness/Sedation scale (OAA/S). The control group was given 2-3 mg of midazolam for induction and additional 1 mg if required.

    Results: PCS and ACS increased the ease of the procedure and reduced the numbers of sedation failures compared to midazolam sedation (ACS n=0; PCS n=4; midazolam n=20). The ACS group had more deeply sedated patients (OAA/S Level 2), desaturations and obstructed airways than the PCS and midazolam groups. Over 90% of all patients had recovered (Aldrete score≥9) by the time they returned to the ward. PCS resulted in the least fatigue and pain after the procedure. Patients’ preference for PCS and ACS were the same.

    Conclusion: PCS with propofol is superior to midazolam and comparable to ACS. PCS resulted in a rapid recovery, tended to be the safest and was almost as effective as ACS in ensuring a successful examination.

  • 35.
    Nilsson, Andreas
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Bak, Zoltan
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Surgery.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Surgery.
    Letter: Patient controlled sedation using a standard protocol for dressing changes in burns: Patients preference, procedural details and a preliminary safety evaluation. Are studies always adequately powered and analyzed? Response2010In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 36, no 6, p. 948-950Article in journal (Other academic)
    Abstract [en]

    n/a

  • 36.
    Parsons, Bryony N.
    et al.
    University of Liverpool, England .
    Wigley, Paul
    University of Liverpool, England .
    Simpson, Hannah L.
    University of Liverpool, England .
    Williams, Jonathan M.
    University of Liverpool, England .
    Humphrey, Suzie
    University of Liverpool, England .
    Salisbury, Anne-Marie
    University of Liverpool, England .
    Watson, Alastair J. M.
    University of Liverpool, England University of E Anglia, England .
    Fry, Stephen C.
    University of Edinburgh, Scotland .
    O'Brien, David
    Provexis Plc, Scotland .
    Roberts, Carol L.
    University of Liverpool, England Provexis Plc, Scotland .
    O'Kennedy, Niamh
    Provexis Plc, Scotland .
    Keita, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Rhodes, Jonathan M.
    University of Liverpool, England .
    Campbell, Barry J.
    University of Liverpool, England .
    Dietary Supplementation with Soluble Plantain Non-Starch Polysaccharides Inhibits Intestinal Invasion of Salmonella Typhimurium in the Chicken2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 2, p. 87658-Article in journal (Refereed)
    Abstract [en]

    Soluble fibres (non-starch polysaccharides, NSP) from edible plants but particularly plantain banana (Musa spp.), have been shown in vitro and ex vivo to prevent various enteric pathogens from adhering to, or translocating across, the human intestinal epithelium, a property that we have termed contrabiotic. Here we report that dietary plantain fibre prevents invasion of the chicken intestinal mucosa by Salmonella. In vivo experiments were performed with chicks fed from hatch on a pellet diet containing soluble plantain NSP (0 to 200 mg/d) and orally infected with S. Typhimurium 4/74 at 8 d of age. Birds were sacrificed 3, 6 and 10 d post-infection. Bacteria were enumerated from liver, spleen and caecal contents. In vitro studies were performed using chicken caecal crypts and porcine intestinal epithelial cells infected with Salmonella enterica serovars following pre-treatment separately with soluble plantain NSP and acidic or neutral polysaccharide fractions of plantain NSP, each compared with saline vehicle. Bacterial adherence and invasion were assessed by gentamicin protection assay. In vivo dietary supplementation with plantain NSP 50 mg/d reduced invasion by S. Typhimurium, as reflected by viable bacterial counts from splenic tissue, by 98.9% (95% CI, 98.1-99.7; Pless than0.0001). In vitro studies confirmed that plantain NSP (5-10 mg/ml) inhibited adhesion of S. Typhimurium 4/74 to a porcine epithelial cell-line (73% mean inhibition (95% CI, 64-81); Pless than0.001) and to primary chick caecal crypts (82% mean inhibition (95% CI, 75-90); Pless than0.001). Adherence inhibition was shown to be mediated via an effect on the epithelial cells and Ussing chamber experiments with ex-vivo human ileal mucosa showed that this effect was associated with increased short circuit current but no change in electrical resistance. The inhibitory activity of plantain NSP lay mainly within the acidic/pectic (homogalacturonan-rich) component. Supplementation of chick feed with plantain NSP was well tolerated and shows promise as a simple approach for reducing invasive salmonellosis.

  • 37.
    Pena, Cristina
    et al.
    Karolinska Institute, Sweden .
    Virtudes Cespedes, Maria
    Centre Bioengn Biomat and Nanomed CIBER BBN, Spain .
    Bradic Lindh, Maja
    Karolinska Institute, Sweden .
    Kiflemariam, Sara
    Uppsala University, Sweden .
    Mezheyeuski, Artur
    Karolinska Institute, Sweden .
    Edqvist, Per-Henrik
    Uppsala University, Sweden .
    Hagglof, Christina
    Karolinska Institute, Sweden .
    Birgisson, Helgi
    Uppsala University, Sweden .
    Bojmar, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Jirstrom, Karin
    Lund University, Sweden .
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Olsson, Eleonor
    Lund University, Sweden .
    Veerla, Srinivas
    Lund University, Sweden .
    Gallardo, Alberto
    Centre Bioengn Biomat and Nanomed CIBER BBN, Spain .
    Sjoblom, Tobias
    Uppsala University, Sweden .
    Chang, AndyC -M
    University of Sydney, Australia .
    Reddel, Roger R.
    University of Sydney, Australia .
    Mangues, Ramon
    Centre Bioengn Biomat and Nanomed CIBER BBN, Spain .
    Augsten, Martin
    Karolinska Institute, Sweden .
    Ostman, Arne
    Karolinska Institute, Sweden .
    STC1 Expression By Cancer-Associated Fibroblasts Drives Metastasis of Colorectal Cancer2013In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 74, no 4, p. 1287-1297Article in journal (Refereed)
    Abstract [en]

    Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant of cancer-associated fibroblasts (CAF). Elevated expression of PDGF receptors on stromal CAFs is associated with metastasis and poor prognosis, but mechanism(s) that underlie these connections are not understood. Here, we report the identification of the secreted glycoprotein stanniocalcin-1 (STC1) as a mediator of metastasis by PDGF receptor function in the setting of colorectal cancer. PDGF-stimulated fibroblasts increased migration and invasion of cocultured colorectal cancer cells in an STC1-dependent manner. Analyses of human colorectal cancers revealed significant associations between stromal PDGF receptor and STC1 expression. In an orthotopic mouse model of colorectal cancer, tumors formed in the presence of STC1-deficient fibroblasts displayed reduced intravasation of tumor cells along with fewer and smaller distant metastases formed. Our results reveal a mechanistic basis for understanding the contribution of PDGF-activated CAFs to cancer metastasis. Cancer Res; 73(4); 1287-97.

  • 38.
    Persborn, Mats
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Gerritsen, J
    Wageningen University, Netherlands .
    Wallon, Conny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Carlsson, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Akkermans, L M A .
    University of Medical Centre, Netherlands .
    Söderholm, Johan D.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    The effects of probiotics on barrier function and mucosal pouch microbiota during maintenance treatment for severe pouchitis in patients with ulcerative colitis2013In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 38, no 7, p. 772-783Article in journal (Refereed)
    Abstract [en]

    Background less thanbrgreater than less thanbrgreater thanA total of 10-15% of patients with an ileoanal pouch develop severe pouchitis necessitating long-term use of antibiotics or pouch excision. Probiotics reduce the risk of recurrence of pouchitis, but mechanisms behind these effects are not fully understood. less thanbrgreater than less thanbrgreater thanAim less thanbrgreater than less thanbrgreater thanTo examine mucosal barrier function in pouchitis, before and after probiotic supplementation and to assess composition of mucosal pouch microbiota. less thanbrgreater than less thanbrgreater thanMethods less thanbrgreater than less thanbrgreater thanSixteen patients with severe pouchitis underwent endoscopy with biopsies of the pouch on three occasions: during active pouchitis; clinical remission by 4 weeks of antibiotics; after 8 weeks of subsequent probiotic supplementation (Ecologic 825, Winclove, Amsterdam, the Netherlands). Thirteen individuals with a healthy ileoanal pouch were sampled once as controls. Ussing chambers were used to assess transmucosal passage of Escherichia coli K12, permeability to horseradish peroxidase (HRP) and Cr-51-EDTA. Composition and diversity of the microbiota was analysed using Human Intestinal Tract Chip. less thanbrgreater than less thanbrgreater thanResults less thanbrgreater than less thanbrgreater thanPouchitis Disease Activity Index (PDAI) was significantly improved after antibiotic and probiotic supplementation. Escherichia coli K12 passage during active pouchitis [3.7 (3.4-8.5); median (IQR)] was significantly higher than in controls [1.7 (1.0-2.4); P andlt; 0.01], did not change after antibiotic treatment [5.0 (3.3-7.1); P = ns], but was significantly reduced after subsequent probiotic supplementation [2.2 (1.7-3.3); P andlt; 0.05]. No significant effects of antibiotics or probiotics were observed on composition of mucosal pouch microbiota; however, E. coli passage correlated with bacterial diversity (r = -0.40; P = 0.018). Microbial groups belonging to Bacteroidetes and Clostridium clusters IX, XI and XIVa were associated with healthy pouches. less thanbrgreater than less thanbrgreater thanConclusions less thanbrgreater than less thanbrgreater thanProbiotics restored the mucosal barrier to E. coli and HRP in patients with pouchitis, a feasible factor in prevention of recurrence during maintenance treatment. Restored barrier function did not translate into significant changes in mucosal microbiota composition, but bacterial diversity correlated with barrier function.

  • 39.
    Persborn, Mats
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Söderholm, Johan D.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Editorial Material: Commentary: the effects of probiotics on barrier function and mucosal pouch microbiota during maintenance treatment for severe pouchitis in patients with ulcerative colitis - authors reply2013In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 38, no 11-12, p. 1406-1407Article in journal (Other academic)
    Abstract [en]

    n/a

  • 40. Roberts, Carol L.
    et al.
    Keita, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Parsons, Bryony N.
    University of Liverpool, England .
    Prorok-Hamon, Maelle
    University of Liverpool, England .
    Knight, Paul
    University of Liverpool, England .
    Winstanley, Craig
    University of Liverpool, England .
    O´Kennedy, Niamh
    Provexis Plc, Aberdeen, UK.
    Söderholm, Johan D.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Rhodes, Jonathan M.
    University of Liverpool, England .
    Campbell, Barry J.
    University of Liverpool, England .
    Soluble plantain fibre blocks adhesion and M-cell translocation of intestinal pathogens2013In: Journal of Nutritional Biochemistry, ISSN 0955-2863, E-ISSN 1873-4847, Vol. 24, no 1, p. 97-103Article in journal (Refereed)
    Abstract [en]

    Dietary fibres may have prebiotic effects mediated by promotion of beneficial bacteria. This study explores the possibility that soluble plant fibre may also improve health by inhibiting epithelial adhesion and translocation by pathogenic bacteria. We have focussed on soluble non-starch polysaccharide (NSP) from plantain bananas (Musa spp.) which previous studies showed to be particularly effective at blocking Escherichia coli epithelial adherence. In vitro and ex vivo studies assessed the ability of plantain NSP to inhibit epithelial cell adhesion and invasion of various bacterial pathogens, and to inhibit their translocation through microfold (M)-cells and human Peyers patches mounted in Ussing chambers. Plantain NSP showed dose-related inhibition of epithelial adhesion and M-cell translocation by a range of pathogens. At 5 mg/ml, a concentration readily achievable in the gut lumen, plantain NSP inhibited adhesion to Caco2 cells by Salmonella Typhimurium (85.0 +/- 8.2%, Pandlt;.01), Shigella sonnei (46.6 +/- 29.3%. Pandlt;.01), enterotoxigenic E.coli (56.1 +/- 23.7%, Pandlt;.05) and Clostridium difficile (67.6 +/- 12.3%, Pandlt;.001), but did not inhibit adhesion by enteropathogenic E.coli. Plantain NSP also inhibited invasion of Caco2 cells by S. Typhimurium (80.2 +/- 9.7%) and Sh. sonnei (46.7 +/- 13.4%); Pandlt;.01. Plantain NSP, 5 mg/ml, also inhibited translocation of S. Typhimurium and Sh. sonnei across M-cells by 73.3 +/- 5.2% and 46.4 +/- 7.7% respectively (Pandlt;.05). Similarly, S. Typhimurium translocation across Peyers patches was reduced 65.9 +/- 8.1% by plantain NSP (Pandlt;.01). Soluble plantain fibre can block epithelial adhesion and M-cell translocation of intestinal pathogens. This represents an important novel mechanism by which soluble dietary fibres can promote intestinal health and prevent infective diarrhoea. Crown Copyright

  • 41.
    Runström, B.
    et al.
    Falun County Hospital, Sweden .
    Hallböök, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Nyström, P.O.
    Karolinska University Hospital, Huddinge and CLINTEC, Karolinska Institute, Stockholm, Sweden .
    Sjödahl, Rune
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Olaison, G.
    Holbaek Hospital, Denmark and University of Copenhagen, Denmark .
    Outcome of 132 consecutive reconstructive operations for intestinal fistula--staged operation without primary anastomosis improved outcome in retrospective analysis2013In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 102, no 3, p. 152-157Article in journal (Refereed)
    Abstract [en]

    AIM

    To study factors that influenced healing and survival after attempted closure of enterocutaneous fistula.

    MATERIAL AND METHODS:

    Retrospective analysis of prospective data concerning 101 patients operated on 132 instances for 110 enterocutaneous fistulae at two hospitals.

    RESULTS:

    In all, 96 (87%) of the 110 fistulae healed and 92 (91%) patients survived. A total of 9 patients with unhealed fistula died. Multivariate analysis revealed jaundice as an independent factor for both death and failed closure and operation without anastomosis as an independent positive factor for healing. Failure rate was lower after an operation with stoma without anastomosis (6 of 43, 14%) than after an operation with anastomosis (30 of 89, 34%) p = 0.0213. Of the 36 instances with unhealed fistula, 13 (36%) could be ascribed to inadvertent bowel lesions at the reconstructive operation. In addition, univariate analysis revealed that patients with previous multiple laparotomies or with multiple operations for enterocutaneous fistula healed less likely and had higher mortality. A low serum albumin, high white blood cell count, high C-reactive protein concentration, high fistula output, total parenteral nutrition, and operation for recurrent fistula were associated with death together with long operation time and operative bleeding, both indicators of surgical complexity. Over time, staged surgery avoiding anastomosis increased from 27% to 57%. Mortality decreased from 12% to 6%, and healing increased from 73% to 94%.

    CONCLUSIONS:

    Chronic inflammation, malnutrition, and liver failure causing an impaired healing capacity are important reasons for failure. Staged operation without primary anastomosis may allow the patient to reverse this condition and improve outcome. The high surgical complexity is a negative factor that requires careful planning of the operation.

  • 42.
    Rutberg, Hans
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Health and Developmental Care, Patient Safety.
    Borgstedt Risberg, Madeleine
    Östergötlands Läns Landsting, Center for Health and Developmental Care, Center for Public Health.
    Sjödahl, Rune
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Nordqvist, Pernilla
    Östergötlands Läns Landsting, Center for Health and Developmental Care, Patient Safety.
    Valter, Lars
    Östergötlands Läns Landsting, Center for Health and Developmental Care, Center for Public Health.
    Nilsson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Characterisations of adverse events detected in a university hospital: a 4-year study using the Global Trigger Tool method2014In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 4, no 5, p. 004879-Article in journal (Refereed)
    Abstract [en]

    Objectives: To describe the level, preventability and categories of adverse events (AEs) identified by medical record review using the Global Trigger Tool (GTT). To estimate when the AE occurred in the course of the hospital stay and to compare voluntary AE reporting with medical record reviewing. Design: Two-stage retrospective record review. Setting: 650-bed university hospital. Participants: 20 randomly selected medical records were reviewed every month from 2009 to 2012. Primary and secondary outcome measures: AE/1000 patient-days. Proportion of AEs found by GTT found also in the voluntary reporting system. AE categorisation. Description of when during hospital stay AEs occur. Results: A total of 271 AEs were detected in the 960 medical records reviewed, corresponding to 33.2 AEs/1000 patient-days or 20.5% of the patients. Of the AEs, 6.3% were reported in the voluntary AE reporting system. Hospital-acquired infections were the most common AE category. The AEs occurred and were detected during the hospital stay in 65.5% of cases; the rest occurred or were detected within 30 days before or after the hospital stay. The AE usually occurred early during the hospital stay, and the hospital stay was 5 days longer on average for patients with an AE. Conclusions: Record reviewing identified AEs to a much larger extent than voluntary AE reporting. Healthcare organisations should consider using a portfolio of tools to gain a comprehensive picture of AEs. Substantial costs could be saved if AEs were prevented.

  • 43.
    Sebastian, Shaji
    et al.
    Hull and East Yorkshire Hospital NHS Trust, England .
    Hernandez, Vincent
    Complex Hospital University of Vigo, Spain .
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Kariv, Revital
    Tel Aviv Sourasky Medical Centre, Israel .
    Tsianos, Epameinondas
    University of Ioannina, Greece University of Ioannina, Greece .
    Toruner, Murat
    Ankara University, Turkey .
    Marti-Gallostra, Marc
    University Hospital Valle de Hebron, Spain .
    Spinelli, Antonino
    University of Milan, Italy .
    E. van der Meulen-de Jong, Andrea
    Leiden University, Netherlands .
    Saritas Yuksel, Elif
    Katip Celebi University, Turkey .
    Gasche, Christoph
    Medical University of Vienna, Austria .
    Ardizzone, Sandro
    L Sacco University Hospital, Italy .
    Danese, Silvio
    Ist Clin Humanitas, Italy .
    Colorectal cancer in inflammatory bowel disease: Results of the 3rd ECCO pathogenesis scientific workshop (I)2014In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 8, no 1, p. 5-18Article, review/survey (Refereed)
    Abstract [en]

    Epidemiological studies demonstrate an increased risk of colorectal cancer in patients with inflammatory bowel disease (IBD). A detailed literature review was conducted on epidemiology, risk factors, pathophysiology, chemoprevention and outcomes of colorectal cancer (CRC) in IBD as part of the 3rd ECCO scientific pathogenesis workshop.

  • 44.
    Shabo, Ivan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Elkarim, Rihab
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Svanvik, Joar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Macrophage Infiltration in Tumor Stroma is Related to Tumor Cell Expression of CD163 in Colorectal Cancer2014In: Cancer Microenvironment, ISSN 1875-2292, E-ISSN 1875-2284, Vol. 7, no 1, p. 61-69Article in journal (Refereed)
    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.

  • 45.
    Shabo, Ivan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Svanvik, Joar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Breast Cancer Expression of DAP12 is Associated With Skeletal and Liver Metastases and Poor Survival2013In: Clinical Breast Cancer, ISSN 1526-8209, E-ISSN 1938-0666, Vol. 13, no 5, p. 371-377Article in journal (Refereed)
    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.

  • 46.
    Sjödahl, Rune
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Starkhammar, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Causes of death after surgery for colon cancer-impact of other diseases, urgent admittance, and gender2013In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 48, no 10, p. 1160-1165Article in journal (Refereed)
    Abstract [en]

    Objective. In patients with colon cancer, high age and comorbidity is common. In this population-based retrospective study we have investigated causes of death and the influence of urgent operation, and gender on survival. Material and methods. Medical records of 413 patients with verified colon cancer were reviewed. The diagnosis was made during 2000-2006 and operation was performed in 385 patients (93%). Results. The overall 5-year survival after surgery was 48.3%. At the end of the follow-up, 128 patients (54.9%) had verified colon cancer when they died but 105 patients (45.1%) had no signs of colon cancer. Their 5-year survival was 5.5% and 41.9%, respectively (p andlt; 0.0001). Median survival time was significantly shorter after urgent compared with elective admittance, 20.7 months versus 77.9 months, and the 5-year survival 32.4% versus 57.9% (p = 0.0001). The tumor stage at operation was more favorable in patients dying with no signs of colon cancer than in those dying with cancer regarding stage I-II (66.7% versus 16.4%), and stage IV (1.0% versus 53.1%), but not regarding stage III (30.5% versus 29.7%). The overall survival in women who were operated was longer than in men (p = 0.045) as well as survival after elective admittance (p = 0.013). Conclusion. After a median follow-up of 56.1 months almost half of the patients who were dead had died from other causes than colon cancer. Ten percent of those patients had an incorrectly reported diagnosis of colon cancer as cause of death. Urgent admittance was associated with reduced survival time. The median survival time was longer in women than in men.

  • 47.
    Steinvall, Ingrid
    et al.
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Linköping University, Department of Clinical and Experimental Medicine, Plastic Surgery, Hand Surgery and Burns.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Bak, Zoltan
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Incidence of early burn-induced effects on liver functionas reflected by the plasma disappearance rate of indocyanine green: a prospective descriptive cohort study2012In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 38, no 2, p. 214-224Article in journal (Refereed)
    Abstract [en]

    Organ dysfunction and failure are important for burned patients as they increase morbidity and mortality. Recent evidence has suggested that organ injuries are occurring earlier after burns, and are more common, than previously thought. In this study we have assessed the extent to which liver function, assessed by the plasma disappearance rate of indocyanine green (PDRICG), is affected in patients with severe burns. This is a prospective, descriptive exploratory study at a national burn centre. Consecutive adult patients with a total burned body surface area (TBSA%) of 20% or more, were examined prospectively by dynamic (PDRICG) and static liver function tests (plasma: bilirubin concentration, prothrombin complex, and alanine aminotransferase and alkaline phosphatase activities). Early liver dysfunction was common, as assessed by both dynamic (7 of 17) and static liver function tests (6-17 of 17). A regression model showed that changes in PDRICG were associated with age, TBSA%, plasma bilirubin concentration, plasma C-reactive protein concentration, and cardiac index. Persistent and advanced hepatic dysfunction was associated with mortality. The PDRICG seems to give a comprehensive assessment of liver function after major burns. Hepatic dysfunction seems to be as common as dysfunction in other organs. We interpret the recorded effects on liver function as part of a multiple organ dysfunction syndrome, primarily induced by the burn itself. However, this needs to be further investigated.

  • 48.
    Svanvik, Joar
    et al.
    Sahlgrenska Hospital, Gothenburg, Sweden.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Review and rhyme: of birth of cancers and selfish epigenomes2014In: Medical Hypotheses, ISSN 0306-9877, E-ISSN 1532-2777, Vol. 82, no 5, p. 639-640Article in journal (Other academic)
    Abstract [en]

    n/a

  • 49.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Gut immunology: Nanoparticles ferry gut antigens2015In: Nature Nanotechnology, ISSN 1748-3387, E-ISSN 1748-3395, Vol. 10, no 4, p. 298-299Article in journal (Other academic)
    Abstract [en]

    n/a

  • 50.
    Thor, Johan
    et al.
    Högskolan i Jönköping.
    Lundgren, Charlotte
    Linköping University, Department of Culture and Communication, Language and Culture. Linköping University, Department of Culture and Communication, Swedish Studies and Comparative Literature. Linköping University, Faculty of Arts and Sciences.
    Batalden, Paul
    The Dartmouth Institute for Health Policy and Clinical Practice, Dartmouth Medical School, Lebanon, New Hampshire, USA.
    Andersson Gäre, Boel
    Landstinget i Jönköpings län.
    Henriks, Göran
    Landstinget i Jönköpings län.
    Sjödahl, Rune
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL.
    Gabrielsson Järhult, Felicia
    Högskolan i Jönköping, Institutionen för gerontologi.
    Collaborative improvement of cancer care in southeastern Sweden – striving for better patient and population health, better care, and better professional development2012In: Sustainably improving health care: creatively linking care outcomes, system performance and professional development / [ed] Batalden, Paul and Foster, Tina, London: Radcliffe Publishing, 2012Chapter in book (Other academic)
12 1 - 50 of 60
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