| 231. |
- Karnevi, Emelie, et al.
(författare)
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Intratumoural leukocyte infiltration is a prognostic indicator among pancreatic cancer patients with type 2 diabetes
- 2018
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Ingår i: Pancreatology. - : Elsevier BV. - 1424-3903. ; 18:1, s. 85-93
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Tidskriftsartikel (refereegranskat)abstract
- Background: The life expectancy of pancreatic cancer patients remains minimal. The disease progression may be influenced by type 2 diabetes (T2D) and inflammatory status, although important gaps persist around their joint effects on disease outcome. The aim of this study was to investigate the clinical significance of the tumour immune microenvironment on pancreatic cancer prognosis in relation to T2D status. Method: Tumour-infiltrating macrophages, neutrophils and eosinophils were studied in primary pancreatic tumours and paired lymph node metastases in relation to patient and tumour characteristics, T2D status and overall survival in a retrospective cohort of patients with resectable pancreatic cancer in Sweden. Results: Of the 80 included pancreatic cancer patients, 22 (27.2%) had T2D. The diabetic pancreatic cancer patients had significantly higher systemic high white blood cell count than those without diabetes (P = 0.028). Macrophage infiltration levels were higher in lymph node metastases compared with primary tumours (P = 0.040) among pancreatic cancer patients with diabetes. Type 2 diabetes or intra-tumoural leukocyte (macrophage, neutrophil or eosinophil) infiltration alone did not significantly influence pancreatic cancer prognosis. However, among cancer patients with T2D high macrophage or neutrophil tumour-infiltration was associated with a significant reduction in overall survival (adjusted hazard ratio [HR] 7.2; 95% CI 1.5-35.0 and HR 5.4; 95% CI 1.1-26.3, respectively). Conclusion: These results demonstrate associations between T2D and enhanced inflammatory processes with significant implications on survival among pancreatic cancer patients with T2D. Validation in larger independent patient cohorts may identify additional prognostic tools and improved treatment strategies for specific patient subsets.
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| 232. |
- Karnevi, Emelie, et al.
(författare)
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Metformin-mediated growth inhibition involves suppression of the IGF-I receptor signalling pathway in human pancreatic cancer cells.
- 2013
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 13:May,10
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological studies have shown direct associations between type 2 diabetes and obesity, both conditions associated with hyperglycaemia and hyperinsulinemia, and the risk of pancreatic cancer. Up to 80% of pancreatic cancer patients present with either new-onset type 2 diabetes or impaired glucose tolerance at the time of diagnosis. Recent population studies indicate that the incidence of pancreatic cancer is reduced among diabetics taking metformin. In this study, the effects of exposure of pancreatic cancer cells to high glucose levels on their growth and response to metformin were investigated.
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| 233. |
- Karnevi, Emelie, et al.
(författare)
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Tumour-educated macrophages display a mixed polarisation and enhance pancreatic cancer cell invasion.
- 2014
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Ingår i: Immunology and Cell Biology. - : Wiley. - 1440-1711 .- 0818-9641. ; 92:6, s. 543-552
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Tidskriftsartikel (refereegranskat)abstract
- At the time of diagnosis, almost 80% of pancreatic cancer patients present with new-onset type 2 diabetes (T2D) or impaired glucose tolerance. T2D and pancreatic cancer are both associated with low-grade inflammation. Tumour-associated macrophages (TAMs) have a key role in cancer-related inflammation, immune escape, matrix remodelling and metastasis. In this study, the interplay between tumour cells and immune cells under the influence of different glucose levels was investigated. Human peripheral blood mononuclear cells were exposed in vitro to conditioned medium from BxPC-3 human pancreatic cancer cells, in normal (5 mM) or high (25 mM) glucose levels. Flow cytometry analyses demonstrated that tumour-derived factors stimulated differentiation of macrophages, with a mixed classical (M1-like) and alternatively activated (M2-like) phenotype polarisation (CD11c(+)CD206(+)). High-glucose conditions further enhanced the tumour-driven macrophage enrichment and associated interleukin (IL)-6 and IL-8 cytokine levels. In addition, hyperglycaemia enhanced the responsiveness of tumour-educated macrophages to lipopolysaccharide, with elevated cytokine secretion compared with normal glucose levels. Tumour-educated macrophages were found to promote pancreatic cancer cell invasion in vitro, which was significantly enhanced at high glucose. The anti-diabetic drug metformin shifted the macrophage phenotype polarisation and reduced the tumour cell invasion at normal, but not high, glucose levels. In conclusion, this study demonstrates that pancreatic cancer cells stimulate differentiation of macrophages with pro-tumour properties that are further enhanced by hyperglycaemia. These findings highlight important crosstalk between tumour cells and TAMs in the local tumour microenvironment that may contribute to disease progression in pancreatic cancer patients with hyperglycaemia and T2D.Immunology and Cell Biology advance online publication, 25 March 2014; doi:10.1038/icb.2014.22.
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| 234. |
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| 235. |
- Kuras, Magdalena, et al.
(författare)
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Assessing Automated Sample Preparation Technologies for High-Throughput Proteomics of Frozen Well Characterized Tissues from Swedish Biobanks
- 2019
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 18:1, s. 548-556
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Tidskriftsartikel (refereegranskat)abstract
- Large cohorts of carefully collected clinical tissue materials play a central role in acquiring sufficient depth and statistical power to discover disease-related mechanisms and biomarkers of clinical significance. Manual preparation of such large sample cohorts requires experienced laboratory personnel. This carries other possible downsides such as low throughput, high risk of errors, and low reproducibility. In this work, three automated technologies for high-throughput proteomics of frozen sectioned tissues were compared. The instruments evaluated included the Bioruptor for tissue disruption and protein extraction; the Barocycler, which is able to disrupt tissues and digest the proteins; and the AssayMAP Bravo, a microchromatography platform for protein digestion, peptide desalting, and fractionation. Wide varieties of tissue samples from rat spleen, malignant melanoma, and pancreatic tumors were used for the assessment. The three instruments displayed reproducible and consistent results, as was proven by high correlations and low coefficients of variation between technical replicates and even more importantly, between replicates that were processed in different batches or at different time points. The results from this study allowed us to integrate these technologies into an automated sample preparation workflow for large-scale proteomic studies that are currently ongoing. Data are available via ProteomeXchange with identifiers PXD010296 and PXD011295.
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| 236. |
- Kölby, David, et al.
(författare)
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Multifocal intraductal tubulopapillary neoplasm of the pancreas with total pancreatectomy: report of a case and review of literature.
- 2015
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Ingår i: International Journal of Clinical and Experimental Pathology. - 1936-2625. ; 8:8, s. 9672-9680
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Tidskriftsartikel (refereegranskat)abstract
- Intraductal neoplasms of the pancreas are classified as intraductal tubulopapillary neoplasms (ITPNs) and intraductal papillary mucinous neoplasm (IPMNs) in the current WHO classification. ITPN is a rare tumor and there are only a few cases of ITPN reported in the literature. We present the case of an otherwise healthy 42-year-old male, who presented with upper abdominal pain. He was subsequently diagnosed with multifocal ITPN and underwent total pancreatectomy. The pathological report showed invasive growth. The postoperative course was uneventful and the patient received 6 months of adjuvant chemotherapy with gemcitabine-capecitabine. The patient is still alive 19 months after the procedure with no signs of recurrence. Literature review revealed only 30 individual cases of ITPN in the pancreas including our reported case. Mean age was 61 years (16 males/14 females; ratio 1.14:1). Mean tumor size was 3 cm. Immunohistochemical staining was positive for CK-7 in 100% of the patients, CK-19 in 95% and for MUC-1 in 88%. Trypsin was negative in all cases. β-catenin was negative in 94% and MUC-2 was negative in 96% of the cases. BRAF, KRAS, TP53 and PIK3CA mutations were infrequently seen. Invasive growth was present in 54% of the cases. Tumor size and Ki-67 index showed a statistically significant association with invasive growth. Survival rate could not be determined, due to short follow-up, and further research is needed to establish prognostic factors for disease recurrence and survival.
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| 237. |
- Landahl, Per, et al.
(författare)
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Severe Acute Pancreatitis: Gut Barrier Failure, Systemic Inflammatory Response, Acute Lung Injury, and the Role of the Mesenteric Lymph.
- 2015
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Ingår i: Surgical Infections. - : Mary Ann Liebert Inc. - 1557-8674 .- 1096-2964. ; 16:6, s. 651-656
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Forskningsöversikt (refereegranskat)abstract
- Severe acute pancreatitis (AP) often leads to distant organ dysfunction with a high morbidity and mortality rate. The most common and earliest organ to fail is the lungs, but the exact pathophysiological mechanisms underlying the disease are still unclear. No successful targeted therapy exists, and treatment is limited to organ supportive care. It is believed that the gut is involved in the development of distant organ failure, as severe AP is associated with changes in the microcirculation, gut permeability/motility, bacterial translocation, and activation of the gut-associated lymphoid tissue (GALT). Experimental evidence implicates the mesenteric lymph as a primary route for these toxic factors to gain access to the systemic circulation. This literature overview was made to survey these mechanisms and the potential of surgical interventions on the thoracic duct as a means of therapy.
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| 238. |
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| 239. |
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| 240. |
- Leveau, Per, et al.
(författare)
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Percutaneous cholecystostomy: a bridge to surgery or definite management of acute cholecystitis in high-risk patients?
- 2008
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 43:5, s. 593-596
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Cholecystectomy is the standard treatment for acute cholecystitis, but in high-risk patients with serious comorbidity and in patients of advanced age there is substantial morbidity and mortality associated with the intervention. In these selected patients, percutaneous cholecystostomy (PCS) is an alternative mode of management. The aim of the present study was to evaluate the outcome of PCS in selected patients with acute cholecystitis. MATERIAL AND METHODS: Thirty-five patients, representing 0.6% of all acute cholecystitis patients managed during the period 1994-2003, were subjected to PCS. Patients' charts were reviewed retrospectively for age, gender, comorbidity, hospital stay, procedure, complications and final outcome, including requirement of additional interventions. RESULTS: PCS was considered successful in 34/35 patients, 26 of whom responded within 3 days. Two patients required additional cholecystectomy 3 days and 20 months, respectively, after the PCS procedure. Two patients underwent endoscopic retrograde cholangiopancreatography (ERCP) and one patient underwent rotation lithotripsy. Four patients suffered recurrent biliary complaints after the acute episode of cholecystitis, while the only serious procedure-related complication was bile leakage from the gallbladder in one patient, which necessitated cholecystectomy. CONCLUSIONS: PCS is a comparatively safe and efficient procedure in the treatment of acute cholecystitis in high-risk patients with serious comorbidity and in elderly patients, contraindicating the general anaesthesia required for laparoscopic or open cholecystectomy.
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