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- Gasslander, Thomas, 1952-
(författare)
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Long-term effects of cholecystokinin on exocrine and endocrine pancreas
- 1991
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The gastrointestinal hormone cholecystokinin (CCK) is known to be oneof the most potent stimulators of pancreatic growth. CCK is alsosuggested to be an initiator and/or promotor of pancreatic carcinogenesis. This study was undertaken to elucidate the effects oflong-term stimulation with exogenous and endogenous CCK andexogenous secretin on exocrtne and endocrine pancreatic cell proliferation (in rats and mice) and on . endocrine (B-cell) function (inrats). Cell kinetics were studied autoradiographically by means of 3H-thymidine labeling of DNA synthesizing cells and endogenous increasein plasma CCK level was induced by surgical pancreatico-biliary diversion (PBD). The study showed that long-term stimulation with the CCK analogue cerulein (in mice) as well as endogenously induced hyperCCKemia (in rats) induced pancreatic hyperplasia. The proliferative response was as high, or even higher, in the ductal and centroacinar cell populations than in the acinar one, which traditionally is regarded as the target forCCK. The cells adapt to the continuous CCK stimulation with a decrease in proliferative activity to control level after 14-20 days. Cerulein seems to induce early changes in the centroacinar cell region with signs of transition of cells from acinar to centroacinar position. Secretin, which has the ductal cells as its main target cell, had no growth stimulating effect on any of the studied cell types. Long-term endogenous CCK stimulation does not affect the proliferation of cells in the islands of Langerhans, nor affect the insulin secretory response or the glucose elimination following intravenous glucose loading. The results of the study are of special interest as human pancreatic carcinoma is considered to be ductal and as there are suggestions of early changes in the centroacinar · region in experimental pancreatic carcinogenesis. Funhermore, the PBD model was found to be suitable for studies on longterm CCK effects, as the pancreatic growth response following PBD was exclusively caused by the increased plasma CCK level.
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- Johansen, Karin, et al.
(författare)
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High resection rate improves overall survival in elderly patients with pancreatic head cancer - A cohort study
- 2021
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Ingår i: International Journal of Surgery Open. - : Elsevier Science Ltd. - 2405-8572. ; 34
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is evidence that a high hospital volume of pancreaticoduodenectomy improves short-and long-term outcomes, but there are few population-based studies on the effect of a high resection rate in the population. The aim of this national, observational study was primarily to investigate differences in overall survival among elderly patients with cancer in the pancreatic head between high and low resection rate groups and secondarily to determine if counties with high resection rates of pancreaticoduodenectomy had more severe complications after surgery. Materials and methods: All patients in the Swedish National Registry for tumours in the pancreatic and periampullary region diagnosed between 2010 and 2018 with pancreatic head cancer were included in this retrospective cohort study. Patients were divided into low and high resection rate groups according to the yearly resection rates in the respective counties. For operative outcomes, all patients who had undergone pancreaticoduodenectomy were included regardless of diagnosis. The primary outcome of the study was overall survival among patients aged >= 70 years with pancreatic head cancer. Results: Among 13 933 patients in the registry, 7661 were 70 years or older, of whom 3006 had pancreatic head cancer. Overall survival was longer in high resection rate groups for patients aged >= 70 years, as for the age subgroups 70-79 years and >= 80 years (all p < 0.001). Among patients who had undergone pancreaticoduodenectomy aged >= 80 years the high resection rate counties showed an increased rate of severe complications, but no increase in 90-day mortality. Conclusion: High resection rate groups show a significantly longer overall survival among elderly patients with pancreatic head cancer in Sweden. This implies that there could be a survival benefit from increasing resections in low resection rate groups. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of Surgical Associates Ltd.
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- Johansen, Karin, 1990-, et al.
(författare)
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Laparoscopic distal pancreatectomy is more cost-effective than open resection: results from a Swedish randomized controlled trial
- 2023
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Ingår i: HPB. - : ELSEVIER SCI LTD. - 1365-182X .- 1477-2574. ; 25:8, s. 972-979
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundLaparoscopic distal pancreatectomy is being implemented worldwide. The aim of this study was to perform a cost-effectiveness analysis from a health care perspective.MethodsThis cost-effectiveness analysis was based on the randomized controlled trial LAPOP, where 60 patients were randomized to open or laparoscopic distal pancreatectomy. For the follow-up of two years, resource use from a health care perspective was recorded, and health-related quality of life was assessed using the EQ-5D-5L. The per-patient mean cost and quality-adjusted life years (QALYs) were compared using nonparametric bootstrapping.ResultsFifty-six patients were included in the analysis. The mean health care costs were lower, €3863 (95% CI: -€8020 to €385), for the laparoscopic group. Postoperative quality of life improved with laparoscopic resection and resulted in a gain in QALYs of 0.08 (95% CI: −0.09 to 0.25). The laparoscopic group had lower costs and improved QALYs in 79% of bootstrap samples. With a cost-per-QALY threshold of €50 000, 95.4% of the bootstrap samples were in favour of laparoscopic resection.ConclusionLaparoscopic distal pancreatectomy is associated with numerically lower health care costs and improvements in QALYs compared with the open approach. The results support the ongoing transition from open to laparoscopic distal pancreatectomies.
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- Johansen, Karin, 1990-, et al.
(författare)
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There Is No Increase in Perioperative Mortality After Pancreaticoduodenectomy in Octogenarians : Results From the Swedish National Registry for Tumors in the Pancreatic and Periampullary Region
- 2020
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Ingår i: Annals of Surgery Open. - : Wolters Kluwer. - 2691-3593. ; 1:2
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this observational study was to compare postoperative mortality and complications between octogenarians and younger patients following pancreaticoduodenectomy (PD).Summary Background Data: With the growing elderly population and improved operative and postoperative results, PD is performed more frequently in octogenarians. Despite recent studies, it is uncertain whether elderly patients experience worse postoperative outcomes than younger patients.Methods: All patients registered in the Swedish National Registry for tumors in the pancreatic and periampullary region from 2010 to 2018 who underwent PD were included in the analysis.Results: Out of 13,936 patients included in the registry, 2793 patients underwent PD and were divided into the following age groups: <70 (n = 1508), 70–79 (n = 1137), and ≥80 (n = 148) years old. There was no significant difference in in-hospital, 30- or 90-day mortality among groups. The 2 older groups had a higher rate of medical and some surgical complications but not a significantly higher rate of complications ≥IIIa according to the Clavien-Dindo classification system. The 2 older groups had lower body mass index, higher American Society of Anesthesiologists and Eastern Cooperative Oncology Group scores, lower smoking rates, and a higher rate of preoperative biliary drainage than the <70-year-old group (all P < 0.001). The operation time was shorter in the oldest group.Conclusions: Despite the worse preoperative condition of octogenarians than younger patients, short-term mortality and serious complications were not increased. The shorter operation time, however, may indicate that patients in the oldest group were more strictly selected. With careful preoperative consideration, especially regarding cardiovascular morbidity, more octogenarians can potentially be safely offered PD.
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- Sandström, Per, 1965-, et al.
(författare)
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Serum amino acid profile in patients with acute pancreatitis
- 2008
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Ingår i: Amino Acids. - : Springer Science and Business Media LLC. - 0939-4451 .- 1438-2199. ; 35:1, s. 225-231
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Tidskriftsartikel (refereegranskat)abstract
- Patients in the early phase of acute pancreatitis (AP) have reduced serum levels of arginine and citrulline. This may be of patho-biological importance, since arginine is the substrate for nitric oxide, which in turn is involved in normal pancreatic physiology and in the inflammatory process. Serum amino acid spectrum was measured daily for five days and after recovery six weeks later in 19 patients admitted to the hospital for acute pancreatitis. These patients had abnormal levels of most amino acids including arginine, citrulline, glutamine and glutamate. Phenylalanine and glutamate were increased, while arginine, citrulline, ornithine and glutamine were decreased compared to levels after recovery. NO2/NO3 concentration in the urine, but not serum arginase activity, was significantly increased day 1 compared to day 5 after admission. Acute pancreatitis causes a disturbance of the serum amino acid spectrum, with possible implications for the inflammatory process and organ function both in the pancreas and the gut. Supplementation of selected amino acids could possibly be of value in this severe condition. © 2007 Springer-Verlag.
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- Trulsson, Lena, 1950-, et al.
(författare)
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Cholecystokinin-8-induced hypoplasia of the rat pancreas : Influence of nitric oxide on cell proliferation and programmed cell death
- 2004
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - 1742-7835 .- 1742-7843. ; 95:4, s. 183-190
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Tidskriftsartikel (refereegranskat)abstract
- The background of cholecystokinin-8 (CCK-8)-induced hypoplasia in the pancreas is not known. In order to increase our understanding we studied the roles of nitric oxide and NF-κB in rats. CCK-8 was injected for 4 days, in a mode known to cause hypoplasia, and the nitric oxide formation was either decreased by means of Nω-nitro-L-arginine (L-NNA) or increased by S-nitroso-N-acetylpencillamine (SNAP). The activation of NF-κB was quantified by ELISA detection, apoptosis with caspase-3 and histone-associated DNA-fragmentation and mitotic activity in the acinar, centroacinar and ductal cells were visualized by the incorporation of [3H]-thymidine. Pancreatic histology and weight as well as protein- and DNA contents were also studied. Intermittent CCK injections reduced pancreatic weight, protein and DNA contents and increased apoptosis, acinar cell proliferation and nuclear factor κB (NF-κB) activation. It also caused vacuolisation of acinar cells. The inhibition of endogenous nitric oxide formation by L-NNA further increased apoptosis and NF-κB activation but blocked the increased proliferation and vacuolisation of acinar cells. The DNA content was not further reduced. SNAP given together with CCK-8 increased apoptosis and other pathways of cell death, raised proliferation of acinar cells and strongly reduced the DNA content in the pancreas. Histological examination showed no inflammation in any group. We conclude that during CCK-8-induced pancreatic hypoplasia, endogenously formed nitric oxide suppresses apoptosis but increases cell death along non-apoptotic pathways and stimulates regeneration of acinar cells. Exogenous nitric oxide enhances the acinar cell turnover by increasing both apoptotic and non-apoptotic cell death and cell renewal. In this situation NF-κB activation seems not to inhibit apoptosis nor promote cell proliferation.
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- Trulsson, Lena M., 1950-, et al.
(författare)
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Cholecystokinin octapeptide induces both proliferation and apoptosis in the rat pancreas
- 2001
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Ingår i: Regulatory Peptides. - 0167-0115 .- 1873-1686. ; 98:1-2, s. 41-48
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Tidskriftsartikel (refereegranskat)abstract
- Cholecystokinin-8 (CCK-8) causes exocrine pancreatic hypertrophy and hyperplasia. High doses of the CCK analogue cerulein causes necrosis and an inflammatory response in the pancreas. We have studied the pancreatic growth response in rats after administration of CCK-8 for 3 days, given either intermittently (20–80 μg/kg) twice a day, or continuously (2.4–48 μg/kg per 24 h). Plasma CCK-8 levels, pancreatic wet weight, water, protein and DNA contents and the pancreatic caspase-3 activity were measured. Cell proliferation was visualized by [3H]thymidine incorporation and apoptosis by TUNEL reaction. Continuous administration of CCK-8 dose-dependently increased the plasma CCK levels, the pancreatic wet weight, protein and DNA contents as well as thymidine labeling index, apoptotic index and caspase-3 activity. Intermittent injections of CCK-8 caused transient raises in plasma CCK, increased apoptotic index and caspase-3 activity, a dose-dependent increase in thymidine labeling but caused a dose-dependent reduction of pancreatic wet weight, protein, and DNA contents. It is concluded that CCK-8 causes both increased proliferation and apoptosis in the pancreas. In case of continuous administration of CCK-8, the proliferation outweighs the apoptosis causing hyperplasia but in the case of intermittent administration the opposite effect is seen.
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