| 1. |
- Slind Olsen, Renate
(författare)
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Circulating and genetic factors in colorectal cancer : Potential factors for establishing prognosis?
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Colorectal cancer (CRC) is defined as a cancer appearing in the colon or in the rectum. In Sweden, ~ 6300 individuals were diagnosed with the disease in 2014 and ~ 2550 individuals diagnosed with CRC die each year due to their cancer. Surgery is the main treatment option of CRC and a survival rate of ~ 10 % is estimated if distant metastases have developed. It is therefore of importance to find factors that may be useful together with tumour, node, metastasis (TNM) stage to establish early CRC diagnosis, prognosis and follow-up of CRC patients. The aim of this thesis was to study the possible association of CD93, PLA2G4C, PDGF-D and inflammatory cytokines with CRC disease progression.In a prospective study approach CD93 and PLA2G4C single nucleotide polymorphisms (SNPs) were of potential importance in CRC prognosis.The T/T genotype of CD93 was associated with an increased CD93 expression in CRC tissue. Further, CRC patients carrying this genotype were associated with disseminated CRC at diagnosis and a lower recurrence-free survival after surgery. The A allele of a SNP of PLA2G4C was a stronger predictor for CRC-specific mortality than the conventional risk factors used in the clinic for selection of TNM stage II patients for adjuvant treatment. This indicates that the T/T genotype of CD93 and the A allele of PLA2G4C may be potential genetic factors related to disease severity and spread. Furthermore, they distinguish CRC patients that may benefit from a more comprehensive follow-up and adjuvant treatment.To study the putative involvement of PDGF-D in CRC the effects of PDGF-D signalling was studied in vitro. PDGF-D signalling altered the expression of genes of importance in CRC carcinogenesis and proliferation which was blocked by imatinib, a tyrosine kinase inhibitor. This indicates that PDGF-D signalling may be an important pathway in CRC progression and a potential target in CRC treatment.The analysis of various inflammatory cytokines in plasma at diagnosis showed an association between high levels and increased total- or CRC-specific mortality two years after surgery. High levels of CCL1 and CCL24 was the only cytokines strongly correlated with a worse CRC prognosis after statistical adjustments and may be of interest for further evaluation.In conclusion, this thesis presents circulating and genetic factors such as CD93, PLA2G4C, PDGF-D, CCL1 and CCL24 that may be of importance in CRC progression and may be of clinical value together with TNM stage in establishing prognosis.
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| 2. |
- Shamoun, Levar, et al.
(författare)
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Association study on IL-4, IL-4Rα and IL-13 genetic polymorphisms in Swedish patients with colorectal cancer
- 2018
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Ingår i: Clinica Chimica Acta. - : Elsevier. - 0009-8981 .- 1873-3492. ; 487, s. 101-106
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Interleukin 4 (IL-4) and interleukin 13 (IL-13) are anti-inflammatory and immunomodulatory cytokines which share a common cellular receptor IL4Rα and are involved in the same signaling pathways. Our purpose was to assess whether genetic variants within IL-4, IL-13 and IL-4Rα are associated with the risk or clinical outcome of colorectal cancer (CRC).METHODS: Three single nucleotide polymorphisms (SNPs) were screened in 466 patients with CRC and 445 healthy controls. The selected SNPs were IL-4 SNP rs2243250, IL-4Rα SNP rs1801275 and IL-13 SNP rs1800925.RESULTS: We found that the genotype variant T/T in IL-13 gene was associated with a higher risk of CRC. Kaplan-Meier analysis showed that the cancer specific survival differed between C/C and CT + TT for IL-4 SNP. Moreover, the carriers of the T allele were associated with the highest risk of CRC death with a hazard ratio (HR) of 1.57, 95% CI 1.06-2.36, p = .024. The observed effect of the T allele was restricted to stage III patients.CONCLUSION: Our results indicate IL-13 SNP rs1800925 as a risk factor for CRC and that IL-4 SNP rs2243250 could be a useful prognostic marker in the follow-up and clinical management of patients with CRC especially in stage III disease.
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| 3. |
- Dominguez-Munoz, J. Enrique, et al.
(författare)
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Recommendations from the United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis
- 2018
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Ingår i: Pancreatology. - : Elsevier BV. - 1424-3903. ; 18:8, s. 847-854
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Forskningsöversikt (refereegranskat)abstract
- Background: In collaboration with United European Gastroenterology, the working group on ‘Harmonizing diagnosis and treatment of chronic pancreatitis across Europe’ (HaPanEU) developed European guidelines for the management of chronic pancreatitis using an evidence-based approach. Methods: Recommendations of multidisciplinary review groups based on systematic literature reviews to answer predefined clinical questions are summarised. Recommendations are graded using the Grading of Recommendations Assessment, Development and Evaluation system. Results: Recommendations covered topics related to the clinical management of chronic pancreatitis: aetiology, diagnosis of chronic pancreatitis with imaging, diagnosis of pancreatic exocrine insufficiency, surgical therapy, medical therapy, endoscopic therapy, treatment of pancreatic pseudocysts, pancreatic pain, nutrition and malnutrition, diabetes mellitus and the natural course of the disease and quality of life. Conclusions: The HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects of the medical and surgical management of chronic pancreatitis based on current available evidence. These recommendations should serve as a reference standard for existing management of the disease and as a guide for future clinical research. This article summarises the HaPanEU recommendations and statements.
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| 4. |
- Abdalla, Maie, et al.
(författare)
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Anorectal Function After Ileo-Rectal Anastomosis Is Better than Pelvic Pouch in Selected Ulcerative Colitis Patients
- 2020
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Ingår i: Digestive Diseases and Sciences. - : Springer-Verlag New York. - 0163-2116 .- 1573-2568. ; , s. 250-259
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: With a lifelong perspective, 12% of ulcerative colitis patients will need a colectomy. Further reconstruction via ileo-rectal anastomosis or pouch can be affected by patients' perspective of their quality of life after surgery.AIM: To assess the function and quality of life after restorative procedures with either ileo-rectal anastomosis or ileal pouch-anal anastomosis in relation to the inflammatory activity on endoscopy and in biopsies.METHOD: A total of 143 UC patients operated with subtotal colectomy and ileo-rectal anastomosis or pouches between 1992 and 2006 at Linköping University Hospital were invited to participate. Those who completed the validated questionnaires (Öresland score, SF-36, Short Health Scale) were offered an endoscopic evaluation including multiple biopsies. Associations between anorectal function and quality of life with type of restorative procedure and severity of endoscopic and histopathologic grading of inflammation were evaluated.RESULTS: Some 77 (53.9%) eligible patients completed questionnaires, of these 68 (88.3%) underwent endoscopic evaluation after a median follow-up of 12.5 (range 3.5-19.4) years after restorative procedure. Patients with ileo-rectal anastomosis reported better overall Öresland score: median = 3 (IQR 2-5) for ileo-rectal anastomosis (n = 38) and 10 (IQR 5-15) for pouch patients (n = 39) (p < 0.001). Anorectal function (Öresland score) and endoscopic findings (Baron-Ginsberg score) were positively correlated in pouch patients (tau: 0.28, p = 0.006).CONCLUSION: Patients operated with ileo-rectal anastomosis reported better continence compared to pouches. Minor differences were noted regarding the quality of life. Ileo-rectal anastomosis is a valid option for properly selected ulcerative colitis patients if strict postoperative endoscopic surveillance is carried out.
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| 5. |
- Ansari, Daniel, et al.
(författare)
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Diagnosis and management of duodenal perforations : a narrative review
- 2019
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 54:8, s. 939-944
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Forskningsöversikt (refereegranskat)abstract
- Duodenal perforation is a rare, but potentially life-threatening injury. Multiple etiologies are associated with duodenal perforations such as peptic ulcer disease, iatrogenic causes and trauma. Computed tomography with intravenous and oral contrast is the most valuable imaging technique to identify duodenal perforation. In some cases, surgical exploration may be necessary for diagnosis. Specific treatment depends upon the nature of the disease process that caused the perforation, the timing, location and extent of the injury and the clinical condition of the patient. Conservative management seems to be feasible in stable patients with sealed perforations. Immediate surgery is required for patients presenting with peritonitis and/or intra-abdominal sepsis. Minimally invasive techniques are safe and effective alternatives to conventional open surgery in selected patients with duodenal perforations. Here we review the current literature on duodenal perforations and discuss the outcomes of different treatment strategies.
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| 6. |
- Risto, Anton, et al.
(författare)
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Reoperations and Long-term Survival of Kock’s Continent Ileostomy in Inflammatory Bowel Disease Patients: A Population Based National Cohort Study from Sweden
- 2023
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Ingår i: Diseases of the Colon & Rectum. - : Wolters Kluwer. - 0012-3706 .- 1530-0358. ; 66:11, s. 1492-1499
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Kock’s continent ileostomy is an option after proctocolectomy for patients not suitable for ileal pouch anal anastomosis or ileorectal anastomosis. Ulcerative colitis is the most common indication for continent ileostomy.OBJECTIVE: The aim of this study was to evaluate the long-term outcome of continent ileostomy.DESIGN: Retrospective cohort register study.SETTINGS: Data were obtained from the Swedish National Patient Registry.PATIENTS: All patients with inflammatory bowel disease and a continent ileostomy were identified. Data on demographics, diagnosis, reoperations, and excisions of the continent ileostomy was obtained. Patients with inconsistent diagnostic coding were classified as inflammatory bowel disease-unclassified.MAIN OUTCOME MEASURES: The main outcome measures was number of reoperations, time to reoperations and time to excision of continent ileostomy.RESULTS: We identified 727 patients, 428 (59%) with ulcerative colitis, 45 (6%) with Crohn’s disease and 254 (35%) with inflammatory bowel disease-unclassified. After a median follow-up time of 27 (IQR, 21-31) years 191 (26%) patients had never had revisional surgery. Some 1,484 reoperations were performed on 536 (74%) patients, the median number of reoperations was 1 (IQR, 0-3) per patient. The continent ileostomy was excised in 77 (11%) patients. Reoperation within the first year after reconstruction was associated with higher rate of revisions (IRR, 2.90 p < 0.001) and shorter time to excision (HR 2.38 p < 0.001). Constructing the continent ileostomy after year 2000 was associated with increased revision and excision rates (IRR, 2.7 p < 0.001 and HR 2.74 p = 0.013). Inflammatory bowel disese-unclassified was associated with increased revisions (IRR, 1.3 p < 0.001) and the proportion of IBD-unclassified patients almost doubled from the 1980s (32%) to after 2000 (50%).LIMITATIONS: Retrospective design, data from register. No data on quality of life available.CONCLUSION: Continent ileostomy is associated with substantial need for revisional surgery, but most patients get to keep their reconstruction for a long time. See Video Abstract at https://links.lww.com/DCR/C122.
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| 7. |
- Torkzad, Michael R., et al.
(författare)
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Impact of COVID-19 on the incidence of CT-diagnosed appendicitis and its complications in the UK and Sweden
- 2022
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Ingår i: International Journal of Colorectal Disease. - : Springer Nature. - 0179-1958 .- 1432-1262. ; 37:6, s. 1375-1383
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Tidskriftsartikel (refereegranskat)abstract
- Aim To compare the number of appendicitis cases and its complications, during the first months of the COVID-19 pandemic in Sweden and the UK and the corresponding time period in 2019. Method Reports of emergency abdominopelvic CT performed at 56 Swedish hospitals and 38 British hospitals between April and July 2020 and a corresponding control cohort from 2019 were reviewed. Two radiologists and two surgeons blinded to the date of cohorts analyzed all reports for diagnosis of appendicitis, perforation, and abscess. A random selection of cases was chosen for the measurement of inter-rater agreement. Result Both in Sweden (6111) and the UK (5591) fewer, abdominopelvic CT scans were done in 2020 compared to 2019 (6433 and 7223, respectively); p < 0.001. In the UK, the number of appendicitis was 36% lower in April-June 2020 compared to 2019 but not in Sweden. Among the appendicitis cases, there was a higher number of perforations and abscesses in 2020, in Sweden. In the UK, the number of perforations and abscesses were initially lower (April-June 2020) but increased in July 2020. There was a substantial inter-rater agreement for the diagnosis of perforations and abscess formations (K = 0.64 and 0.77). Conclusion In Sweden, the number of appendicitis was not different between 2019 and 2020; however, there was an increase of complications. In the UK, there was a significant decrease of cases in 2020. The prevalence of complications was lower initially but increased in July. These findings suggest variability in delay in diagnosis of appendicitis depending on the country and time frame studied.
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| 8. |
- Aronsson, Linus, et al.
(författare)
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High-density and targeted glycoproteomic profiling of serum proteins in pancreatic cancer and intraductal papillary mucinous neoplasm
- 2018
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 53:12, s. 1597-1603
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Glycoproteomics is an emerging subfield of proteomics. Tumor-specific variations in protein glycosylation might be potential targets for the development of new cancer diagnostics. Here, we performed high-throughput screening and targeted verification of glycome alterations in serum samples from patients with pancreatic cancer and the precancerous lesion intraductal papillary mucinous neoplasm (IPMN). Material and methods: The glycosylation profile of 1000 proteins was mapped in a discovery cohort comprising serum samples from 16 individuals, including 8 patients with pancreatic cancer and 8 healthy controls. The top 10 glycoprotein biomarker candidates with the highest signal intensity difference in glycosylation levels were evaluated in a cohort consisting of 109 serum samples, including 49 patients with resectable pancreatic cancer, 13 patients with resectable noninvasive IPMN and 47 healthy controls, using a targeted assay. Results: Multivariable analysis defined sets of panels comprising CA19-9 and distinctively glycosylated proteins for discrimination between pancreatic cancer, IPMN and healthy controls. A panel including CA 19-9, IL.17E, B7.1 and DR6 gave an AUC of 0.988 at 100% sensitivity at 90% specificity for the discrimination of stage 1 pancreatic cancer and healthy controls. B7.1 was found to be a valuable biomarker for differentiating between IPMN and healthy controls, with better performance alone than CA 19-9. Conclusions: Measurement of protein glycosylation profiles in serum may aid in the early detection of pancreatic cancer and precursor lesions.
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| 9. |
- Byrling, Johannes, et al.
(författare)
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Expression of peritumoral SPARC during distal cholangiocarcinoma progression and correlation with outcome
- 2020
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 55:6, s. 725-731
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Distal cholangiocarcinoma (dCCA) is a malignancy with a dismal prognosis. One of the hallmarks is the presence of a rich desmoplastic stroma believed to contribute to tumor progression and treatment resistance. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein implicated in tumor-stroma interaction with prognostic correlation across several malignancies. The aim of the present study was to evaluate the expression pattern and prognostic significance of SPARC in resected dCCA and paired lymph node metastasis. Materials and methods: SPARC expression was evaluated in 59 resected dCCA samples and 25 paired lymph node metastases as well as 10 benign bile duct samples using immunohistochemistry. Stromal SPARC expression was scored semi quantitatively. Survival was estimated using the Kaplan–Meier method with associated log-rank test. Results: SPARC expression was absent in normal bile ducts. In dCCA, peritumoral stromal SPARC was detectable in 47/59 (80%) of samples with 40/59 (68%) classified as high stromal SPARC expression. There was a significantly lower proportion of SPARC positive stroma in paired lymph node metastasis 17/25 (68%) than the corresponding primary tumors 24/25 (96%) (p =.016). Stromal SPARC expression was associated with the presence of lymph node metastasis; high SPARC expression 31/40 (78%) versus low SPARC expression 9/19 (47%) (p =.013). In the present material there was no significant association between stromal SPARC expression and survival. Conclusions: Stromal SPARC expression occurs frequently in dCCA. Although significantly lower than in primary tumors stromal SPARC is frequently retained in paired lymph node metastasis suggesting a possible role in the metastatic process of dCCA.
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| 10. |
- Hu, Dingyuan, et al.
(författare)
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Galectin 4 is a biomarker for early recurrence and death after surgical resection for pancreatic ductal adenocarcinoma
- 2019
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 54:1, s. 95-100
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Tidskriftsartikel (refereegranskat)abstract
- Background: Galectins are a group of carbohydrate-binding proteins that are involved in neoplastic development and progression. In a previous mass spectrometry-based study, we identified galectin 4 as a down-regulated protein in short-term survivors of pancreatic cancer. This study was performed to validate the prognostic value of galectin 4 in a larger cohort of pancreatic cancer patients undergoing surgical resection. Methods: Galectin 4 expression was evaluated by tissue microarrays and immunohistochemistry in 140 patients with surgically resected pancreatic cancer. Kaplan-Meier and Cox proportional hazards modeling were used to explore the association between galectin 4 and survival. Results: Galectin 4 staining expression was positive in 111 cases (79.3%). The expression of galectin 4 was significantly associated with tumor size (p =.008) and differentiation (p =.001). Galectin 4 expression was significantly correlated with disease recurrence within 1 year of surgery (adjusted HR 0.485, p =.027). There was also a significant association between galectin 4 and overall survival at 1 year (adjusted HR 0.482, p =.047) and at 3 years (adjusted HR 0.550, p =.025). Conclusion: Galectin 4 expression is a novel biomarker for early recurrence and mortality after surgical resection for pancreatic cancer.
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