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31.
  • Larsson, Anna, et al. (författare)
  • Water soluble contrast enema examination of the integrity of the rectal anastomosis prior to loop ileostomy reversal may be superfluous
  • 2015
  • Ingår i: International Journal of Colorectal Disease. - : Springer Science and Business Media LLC. - 1432-1262 .- 0179-1958. ; 30:3, s. 381-384
  • Tidskriftsartikel (refereegranskat)abstract
    • Defunctioning loop ileostomy in low anterior resection (LAR) is routinely used to reduce consequences of anastomotic leakage. The purpose of this study was to analyze which examination technique is optimal for evaluating the integrity of the anastomosis prior to loop ileostomy reversal. Retrospective analysis of 95 patients who had been subjected to LAR at Helsingborg Hospital and SkAyenne University Hospital, Sweden, was undertaken between January 2007 and June 2009. The examination techniques of the rectal anastomosis prior to reversal and the clinical outcome after reversal were studied. Radiologic anastomosis control using water soluble contrast enema, digital rectal examination (DRE), and rectoscopy were performed in 53 % (50/95), 98 % (93/95), and 69 % (66/95), respectively. In two patients, no control of the anastomosis was performed before reversal. Fifty-two percent (49/95) of the patients were examined using all techniques. Six patients demonstrated leakage detected before reversal of which two were only radiological leakages. These two patients underwent loop ileostomy reversal after delay without complications. They were the only ones where the three examination techniques did not prove coherence. Four patients had symptomatic leakage; these were detected with rectoscopy and DRE and verified with enema. Three patients developed anastomotic leakage after loop ileostomy reversal despite normal preoperative examinations. Two of these patients had rectovaginal fistulas (AVFs). This retrospective study indicates that contrast enema does not provide additional information if rectoscopy and DRE are normal. Despite negative examinations, three of nine leakages were diagnosed after loop ileostomy reversal. Especially, AVFs seem difficult to diagnose.
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32.
  • Lepsenyi, Mattias, et al. (författare)
  • CXCL2-CXCR2 axis mediates αV integrin-dependent peritoneal metastasis of colon cancer cells
  • 2021
  • Ingår i: Clinical and Experimental Metastasis. - : Springer Science and Business Media LLC. - 1573-7276 .- 0262-0898. ; 38:4, s. 401-410
  • Tidskriftsartikel (refereegranskat)abstract
    • Peritoneal metastasis is an insidious aspect of colorectal cancer. The aim of the present study was to define mechanisms regulating colon cancer cell adhesion and spread to peritoneal wounds after abdominal surgery. Mice was laparotomized and injected intraperitoneally with CT-26 colon carcinoma cells and metastatic noduli in the peritoneal cavity was quantified after treatment with a CXCR2 antagonist or integrin-αV-antibody. CT-26 cells expressed cell surface chemokine receptors CXCR2, CXCR3, CXCR4 and CXCR5. Stimulation with the CXCR2 ligand, CXCL2, dose-dependently increased proliferation and migration of CT-26 cells in vitro. The CXCR2 antagonist, SB225002, dose-dependently decreased CXCL2-induced proliferation and migration of colon cancer cells in vitro. Intraperitoneal administration of CT-26 colon cancer cells resulted in wide-spread growth of metastatic nodules at the peritoneal surface of laparotomized animals. Laparotomy increased gene expression of CXCL2 at the incisional line. Pretreatment with CXCR2 antagonist reduced metastatic nodules by 70%. Moreover, stimulation with CXCL2 increased CT-26 cell adhesion to extracellular matrix (ECM) proteins in a CXCR2-dependent manner. CT-26 cells expressed the αV, β1 and β3 integrin subunits and immunoneutralization of αV abolished CXCL2-triggered adhesion of CT-26 to vitronectin, fibronectin and fibrinogen. Finally, inhibition of the αV integrin significantly attenuated the number of carcinomatosis nodules by 69% in laparotomized mice. These results were validated by use of the human colon cancer cell line HT-29 in vitro. Our data show that colon cancer cell adhesion and growth on peritoneal wound sites is mediated by a CXCL2-CXCR2 signaling axis and αV integrin-dependent adhesion to ECM proteins.
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33.
  • Lepsenyi, Mattias, et al. (författare)
  • Self-expanding metal stents in malignant colonic obstruction: experiences from Sweden.
  • 2011
  • Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Acute surgery in the management of malignant colonic obstruction is associated with high morbidity and mortality. The use of self-expanding metal stents (SEMS) is an alternative method of decompressing colonic obstruction. SEMS may allow time to optimize the patient and to perform preoperative staging, converting acute surgery into elective. SEMS is also proposed as palliative treatment in patients with contraindications to open surgery. Aim: To review our experience of SEMS focusing on clinical outcome and complications. The method used was a review of 75 consecutive trials at SEMS on 71 patients based on stent-protocols and patient charts. FINDINGS: SEMS was used for palliation in 64 (85%) cases and as a bridge to surgery in 11 (15%) cases. The majority of obstructions, 53 (71%) cases, were located in the recto-sigmoid. Technical success was achieved in 65 (87%) cases and clinical decompression was achieved in 60 (80%) cases. Reasons for technical failure were inability to cannulate the stricture in 5 (7%) cases and suboptimal SEMS placement in 3 (4%) cases. Complications included 4 (5%) procedure-related bowel perforations of which 2 (3%) patients died in junction to post operative complications. Three cases of bleeding after SEMS occurred, none of which needed invasive treatment. Five of the SEMS occluded. Two cases of stent erosion were diagnosed at the time of surgery. Average survival after palliative SEMS treatment was 6 months. CONCLUSION: Our results correspond well to previously published data and we conclude that SEMS is a relatively safe and effective method of treating malignant colonic obstruction although the risk of SEMS-related perforations has to be taken into account.
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34.
  • Loftås, Per, 1964- (författare)
  • Response to neoadjuvant treatment in rectal cancer surgery
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Rectal cancer is one of the three most common malignancies in Sweden with an annual incidence of about 2000 cases. Current treatment consists of surgical resection of the rectum including the loco-regional lymph nodes in the mesorectum. In advanced cases, neoadjuvant chemo-radiotherapy (CRT) prior to the operative treatment reduces local recurrences and enables surgery. The neoadjuvant treatment can also eradicate the tumour completely, i.e. complete response. This research project was designed to investigate the effects of preoperative radiotherapy/ CRT and analyze methods to predict response to CRT.Study I investigated the expression of the FXYD-3 protein with immunohistochemistry in rectal cancer, with or without preoperative radiotherapy. The results from the total cohort showed that, strong FXYD-3 expression was correlated to infiltrative tumour growth (p = 0.02). In the radiotherapy group, strong FXYD-3 expression was related to an unfavourable prognosis (p = 0.02). Tumours with strong FXYD-3 expression had less tumour necrosis (p = 0.02) after radiotherapy. FXYD-3 expression in the primary tumour was increased compared to normal mucosa (p=0.008). We concluded that FXYD-3 expression was a prognostic factor in patients receiving preoperative radiotherapy for rectal cancer.Study II investigated FXYD-3 expression in tumours that developed local recurrences following surgery and compared this with expression in tumours that did not develop local recurrences. There was no difference in the expression of FXYD-3 between the group that developed local recurrences and the group that did not develop local recurrences. There was no difference in survival between those with strong or weak FXYD-3 expression. We concluded that this study could not confirm the findings from study 1 i.e. that FXYD-3 expression has prognostic significance in rectal cancer.Study III was a register-based study on the incidence and effects of complete response to neoadjuvant treatment. Eight per cent of the patients with adequate CRT to achieve complete response also had a complete histological response of the luminal tumor in the resected bowel. Sixteen per cent of that group had remaining lymph node metastases in the operative specimen. Chemotherapy together with radiotherapy doubled the chance of complete response in the luminal tumour. Patients with remaining lymph node metastases had a lower survival rate compared to those without. We concluded that residual nodal involvement after neoadjuvant treatment was an important factor for reduced survival after complete response in the luminal tumour.Study IV followed up the results from the previous study by re-evaluating magnetic resonance imaging (MRI)- images in patients with complete tumour response. Two experienced MRI radiologists performed blinded re-staging of post CRT MR- images from patients with complete response in the luminal tumour. One group with lymph node metastases and another one without were studied and the results compared with the pathology reports. The sensitivity, specificity, and positive and negative predicted values for correct staging of positive lymph nodes was 37%, 84%, 70% and 57%. The size of the largest lymph node (4.5 mm, p=0.04) seemed to indicate presence of a tumour positive lymph node. We concluded that MRI couldn’t correctly stage patients for lymph node metastases in patients with complete response to CRT in the luminal tumour.
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35.
  • Luo, Lingtao, et al. (författare)
  • Pro-inflammatory role of neutrophil extracellular traps in abdominal sepsis.
  • 2014
  • Ingår i: American Journal of Physiology: Lung Cellular and Molecular Physiology. - : American Physiological Society. - 1522-1504 .- 1040-0605. ; 307:7, s. 586-596
  • Tidskriftsartikel (refereegranskat)abstract
    • Excessive neutrophil activation is a major component in septic lung injury. Neutrophil-derived DNA may form extracellular traps in response to bacterial invasions. The aim of the present study was to investigate the potential role of neutrophil extracellular traps (NETs) in septic lung injury. Male C57BL/6 mice were treated with rhDNAse (5 mg/kg) after cecal ligation and puncture (CLP). Extracellular DNA was stained by Sytox green and NET formation was quantified by confocal microscopy and cell-free DNA in plasma, peritoneal cavity and lung. Blood, peritoneal fluid and lung tissue were harvested for analysis of neutrophil infiltration, NET levels, tissue injury as well as CXC chemokine and cytokine formation. We observed that CLP caused increased formation of NETs in the plasma, peritoneal cavity and lung. Administration of rhDNAse not only eliminated NET formation in the plasma, peritoneal cavity and bronchoalveolar space but also reduced lung edema and tissue damage 24 h after CLP induction. Moreover, treatment with rhDNAse decreased CLP-induced formation of CXC chemokines, IL-6 and HMGB1 in the plasma as well as CXC chemokines and IL-6 in the lung. In vitro, we found that neutrophil-derived NETs had the capacity to stimulate secretion of CXCL2, TNF-α and HMGB1 from alveolar macrophages. Taken together, our findings show that NETs regulate pulmonary infiltration of neutrophils and tissue injury via formation of pro-inflammatory compounds in abdominal sepsis. Thus, we conclude that NETs exert a pro-inflammatory role in septic lung injury.
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36.
  • Lurvink, R.J, et al. (författare)
  • The Delphi and GRADE methodology used in the PSOGI 2018 consensus statement on Pseudomyxoma Peritonei and Peritoneal Mesothelioma
  • 2021
  • Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983. ; 47:1, s. 4-10
  • Forskningsöversikt (refereegranskat)abstract
    • Pseudomyxoma Peritonei (PMP) and Peritoneal Mesothelioma (PM) are both rare peritoneal malignancies. Currently, affected patients may be treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy offering long-term survival or even cure in selected patients. However, many issues regarding the optimal treatment strategy are currently under debate. To aid physicians involved in the treatment of these patients in clinical decision making, the PSOGI executive committee proposed to create a consensus statement on PMP and PM. This manuscript describes the methodology of the consensus process. The Delphi technique is a reliable method for attaining consensus on a topic that lacks scientific evidence through multiple voting rounds which feeds back responses to the participants in between rounds. The GRADE system provides a structured framework for presenting and grading the available evidence. Separate questionnaires were created for PMP and PM and sent during two voting rounds to 80 and 38 experts, respectively. A consensus threshold of 51.0% was chosen. After the second round, consensus was reached on 92.9%–100.0% of the questions. The results were presented and discussed in the plenary session at the PSOGI 2018 international meeting in Paris. A third round for the remaining issues is currently in progress. In conclusion, using the Delphi technique and GRADE methodology, consensus was reached in many issues regarding the treatment of PM and PMP amongst an international panel of experts. The main results will be published in the near future.
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37.
  • Mangell, Peter, et al. (författare)
  • Lactobacillus plantarum 299v Does Not Reduce Enteric Bacteria or Bacterial Translocation in Patients Undergoing Colon Resection.
  • 2012
  • Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 1573-2568 .- 0163-2116. ; 57:7, s. 1915-1924
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Probiotics may exert beneficial effects in the gastrointestinal tract. This randomized trial investigated the effect of the probiotic Lactobacillus plantarum 299v on the intestinal load of potentially pathogenic bacteria, bacterial translocation, and cell proliferation in elective colon surgery. METHODS: Seventy-five patients were randomized to pre- and postoperative oral intake of Lactobacillus plantarum 299v or placebo. Rectal swabs and mucosal biopsies were taken before the start of intake, after 1 week, at surgery, and after 6 days, weeks, and months. Viable counts were quantified for clostridia, Enterobacteriaceae, Gram-negative anaerobes, and lactobacilli. Bacterial translocation was determined by the analysis of bacterial DNA genes in mesenteric lymph nodes. Ki-67 was used as a marker of cell proliferation in normal mucosa and tumor. RESULTS: Lactobacillus plantarum 299v was given without adverse effects. Lactobacillus plantarum 299v as well as Enterobacteriaceae and Gram-negative anaerobes increased in the colon 1 week after the administration of Lactobacillus plantarum 299v. There were no significant differences between patients receiving Lactobacillus plantarum 299v and placebo in the incidence of bacterial translocation (27 vs. 13 %) and postoperative complications (16 vs. 31 %). CONCLUSIONS: Lactobacillus plantarum 299v was established in the intestine, but no inhibitory effect on enteric bacteria, bacterial translocation, or postoperative complications was found. The mechanism behind the protective effects of probiotics found in animal and some human studies remain elusive and require further explorations. No adverse effects were recorded after the administration of high doses of Lactobacillus plantarum 299v.
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38.
  • Näsvall, Pia, 1967- (författare)
  • Parastomal hernia : investigation and treatment
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • BackgroundParastomal hernia is a common stoma complication causing the patient considerable inconvenience. The patient becomes aware of a bulge around the stoma, but a bulge is not always a parastomal hernia and diagnostics must be performed to enable differential treatment. It is difficult to distinguish between a bulge and a hernia. Results based on clinical examination and computerised tomography (CT) in the supine position, have not been convincing. Three-dimensional intrastomal ultrasonography (3D US) is a novel technique shown to be promising in the assessment of stoma complaints. Two studies were performed to determine inter- and intra-observer reliability as well as the validity of 3D US as an alternative to CT when assessing stoma complaints.There are numerous options for the treatment of parastomal hernia, but none has been shown superior. In the recent decades the use of mesh in the repair of incisional and inguinal hernia has become routine. New materials must be evaluated as there are potential morbidity and even mortality risks with mesh repair. As recurrence of a parastomal hernia is an even greater challenge, the method of choice should have a low risk for recurrence. A prospective multicenter study was performed to evaluate safety and recurrence rate when using Parastomal Hernia Patch BARDTM (PHP), a mesh specially designed for parastomal hernia repair.A stoma has a profound impact on the patient´s daily life, both physical and psychological. A parastomal hernia with its associated risk for leakage and incarceration worsens the situation. Patient driven assessment of healthcare outcome is important if we are to improve medical care. A quality of life (QoL) survey was performed to assess the impact of parastomal bulging and hernia on the patient´s daily life.MethodsForty patients were investigated and the 3D US images were twice evaluated by two or three physicians to assess inter- and intra-observer reliability. Totally 20 patients with stoma complaints requiring surgery were examined with CT and 3D US prior to surgery. The findings were compared with the intraoperative findings – regarded as the true outcome.Fifty patients with parastomal hernia requiring surgery were enrolled from three hospitals. Patients were followed up one month and one year after repair using PHP.Patients still alive in 2008 who had been operated between1996 and 2004 for rectal cancer in Uppsala/Örebro-, Stockholm/Gotland-, and Northern Regions (986 patients) and registered in the Swedish Rectal Cancer Registry (SRCR) were invited to fill in four QoL questionnaires.ResultsInter-observer agreement using 3D US reached 80% for the last 10 patients examined, with a kappa value of 0.70. Intra-observer agreement for two examiners was 80% and 95%. The learning curve levelled out at 30 patients. Both CT and 3D US showed high sensitivity and specificity when compared with intraoperative findings.After surgery for parastomal hernia with a PHP, the complication rate at one month was 30% and recurrence rate at one year was 22%. Twelve patients were reoperated within one year.In the QoL study, 31.5% of the patients with a stoma reported a bulging or a hernia. 11.7% had been operated for parastomal hernia. A hernia or a bulge gave rise to significantly more pain and impaired stoma function. Overall QoL was inferior in patients with a permanent stoma compared to a group without a stoma.
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39.
  • Näverlo, Simon, 1991- (författare)
  • Stomas from a rural perspective : an evaluation of characteristics, differences and improvement opportunities
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: Stoma-related complications are common and consequences for the individual patient may be considerable. In rural areas, competence regarding stoma-related problems is largely absent. Since the aim of a publicly funded healthcare system is good healthcare on equal terms regardless of where one lives, studies evaluating differences and possible areas of improvement in rural areas are important. An evaluation of stoma-related characteristics, geographic differences and improvement opportunities from a rural perspective has not been done previously. The characteristics and differences studied in this thesis are: stoma reversal; occurrence of permanent stoma; and quality-of-life (QoL).Methods: Epidemiological methods applied to register data were used in Study I. Data extracted from the National Rectal Cancer Register together with socioeconomic data from Statistics Sweden were used. Study II was a cross-sectional study using surveys matched with data from the National Rectal Cancer Register. Study III was based on data from a double-blind randomised controlled trial. Patients were randomised to either a prophylactic mesh or no mesh in order to prevent parastomal hernia (PSH). Quality-of-life was assessed by grouping and comparing results of questionnaires answered by the patients included. In Study IV, a qualitative explorative method was applied to describe the quality of life of rural living stoma patients. Qualitative content analysis was used to analyse data.Aims and Results: Study I investigated whether distance by road to hospital had an impact on the following outcomes: stoma reversal rate; time from index operation to stoma reversal; and occurrence of permanent stoma after rectal cancer surgery. Longer distance to hospital had no effect on these outcomes in a multivariate model. In the univariate logistic regression model results indicated the opposite; patients living closest to the operating hospital had a higher likelihood of no reversal (OR 0.3; 95% CI 0.12–0.76). In northern Sweden, 77 % of all stoma reversals were delayed more than 6 months after index surgery. Stoma reversal was performed up to 1557 days after index surgery, and the shortest time to reversal was 82 days (median 287 days).Study II investigated the impact of distance to nearest hospital on the QoL of rectal cancer patients who had received a stoma at index surgery. Patients living in rural areas reported more pain and sore skin compared to those living closer. When only considering patients who still had a stoma, global QoL was reduced and stoma-related problems were also affected negatively in the rural group.Study III Investigated whether a prophylactic mesh when creating an end colostomy affected QoL. No effect on global QoL was seen at one-year follow up. In several other QoL-parameters mesh patients scored superior compared to non-mesh patients, even when excluding those with a parastomal hernia (PSH).Study IV investigated experiences of living with a stoma in a rural setting, how the process of seeking healthcare was experienced and the problems that occur. Results show that living with a stoma was experienced as a process; an initial sense of hopelessness, especially when suffering from stoma-related problems, progressing to the crucial acceptance of their situation. Stoma leakage was frequently described and experienced as unpleasant and unpredictable. Experiences of seeking healthcare in a rural district varied, some spoke warmly about the care given at the cottage hospital while other expressed dissatisfaction.Conclusions: The notably high rate of delayed reversal of a defunctioning stoma in northern Sweden leads to unnecessary suffering for patients. In view of the long delay in reversal times seen, future studies must have considerably longer follow-up. Rural living rectal cancer patients who receives a stoma reported more pain than those living closer to the nearest hospital. Rectal cancer patients who still had a stoma reported an inferior quality-of-life and more stoma-related problems compared to their town counterparts. Results from the studies in this thesis show that the use of a prophylactic mesh when forming an end colostomy has no impact on subsequent global QoL. Rural living stoma patients commonly experience problems related to their stoma that affect their everyday living. Improved patient education shortly after receiving a stoma could help these patients in coming to terms with their situation.
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40.
  • Olofsson, Fredrik, et al. (författare)
  • No benefit of extended mesenteric resection with central vascular ligation in right-sided colon cancer.
  • 2016
  • Ingår i: Colorectal Disease. - : Wiley. - 1462-8910.
  • Tidskriftsartikel (refereegranskat)abstract
    • The optimal extent of mesenteric resection in colon cancer surgery is not known. We have previously shown an increased mortality associated with wider mesenteric resection in right hemicolectomy. This study compares the short and long-term outcome in three variations of right hemicolectomy based on the position of the vascular ligature in the mesentery.
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