| 51. |
- Månsson, Christopher
(författare)
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Irreversible electroporation of pancreatic adenocarcinoma
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pancreatic cancer (PC) is a severe diagnosis with poor prognosis. Radical surgery is the only treatment that can possibly lead to a cure, and even with surgery, the 5-year survival is only 20%–25%. The majority of patients cannot be resected due to metastases or having a tumour that is too advanced locally (LAPC) with encasement of blood-vessels.Short electrical pulses can change the cell membrane, creating reversible pores in it. With a higher current, the pores become permanent, resulting in irreversible electroporation (IRE). This leads to specific cell death, with the chance to save surrounding scaffold material, such as the walls of blood vessels and bile ducts. This led to the theory that IRE might be suitable for treating LAPC.In Paper I, we found that IRE can be safely performed percutaneously with ultrasound guidance in humans with PC, with promising efficacy, since one of the five patients included was downstaged due to the IRE and could be surgically resected. In Paper II, which is an extension of Paper I, we treated 24 patients with LAPC (3 were also included in Paper I) who had received chemotherapy and, after IRE, stable disease was seen. Median overall survival was 17.9 months. Eleven patients had some form of complication, but we still concluded that IRE is reasonably safe in LAPC patients, with promising efficacy. In Paper III, we chose to treat LAPC with IRE followed by adjuvant chemotherapy. We compared the overall survival of our patients with those with LAPC in the National Quality Registry for Pancreatic and Periampullary Cancer. No significant survival gain could be seen in the group that received IRE compared to the registry group (13.3 months versus 9.9 months, p=0.511). In the IRE group, there were six major complications and we found no support for using IRE in this setting. Paper IV examines the response on the tumour marker CA19-9 in PC treated with IRE. We found 35 patients suitable for this analysis. The hypothesis that IRE would lower the CA19-9 value could not be proven. In fact, the CA19-9 was slightly higher one month after IRE (282 U/ml versus 315 U/ml). However, the 25th percentile of patients with the best CA19-9 response had a better survival (p=0.01) compared to the 25th percentile with the worst response, indicating that CA19-9 can be used as a prognostic marker after IRE in PC.
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| 52. |
- Naudin, Sabine, et al.
(författare)
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Healthy lifestyle and the risk of pancreatic cancer in the EPIC study
- 2020
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 35:10, s. 975-986
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic cancer (PC) is a highly fatal cancer with currently limited opportunities for early detection and effective treatment. Modifiable factors may offer pathways for primary prevention. In this study, the association between the Healthy Lifestyle Index (HLI) and PC risk was examined. Within the European Prospective Investigation into Cancer and Nutrition cohort, 1113 incident PC (57% women) were diagnosed from 400,577 participants followed-up for 15 years (median). HLI scores combined smoking, alcohol intake, dietary exposure, physical activity and, in turn, overall and central adiposity using BMI (HLIBMI) and waist-to-hip ratio (WHR, HLIWHR), respectively. High values of HLI indicate adherence to healthy behaviors. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and 95% confidence intervals (CI). Sensitivity analyses were performed by excluding, in turn, each factor from the HLI score. Population attributable fractions (PAF) were estimated assuming participants’ shift to healthier lifestyles. The HRs for a one-standard deviation increment of HLIBMI and HLIWHR were 0.84 (95% CI: 0.79, 0.89; ptrend = 4.3e−09) and 0.77 (0.72, 0.82; ptrend = 1.7e−15), respectively. Exclusions of smoking from HLIWHR resulted in HRs of 0.88 (0.82, 0.94; ptrend = 4.9e−04). The overall PAF estimate was 19% (95% CI: 11%, 26%), and 14% (6%, 21%) when smoking was removed from the score. Adherence to a healthy lifestyle was inversely associated with PC risk, beyond the beneficial role of smoking avoidance. Public health measures targeting compliance with healthy lifestyles may have an impact on PC incidence.
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| 53. |
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| 54. |
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| 55. |
- Regnér, Sara, et al.
(författare)
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Monocyte Chemoattractant Protein 1, Active Carboxypeptidase B and CAPAP at Hospital Admission Are Predictive Markers for Severe Acute Pancreatitis.
- 2008
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Ingår i: Pancreatology. - : Elsevier BV. - 1424-3903. ; 8:1, s. 42-49
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Tidskriftsartikel (refereegranskat)abstract
- Background: CAPAP, the activation peptide of procarboxypeptidase B, is a predictor of severe acute pancreatitis (AP). Active carboxypeptidase (aCAP) may be a better predictor, as its turnover is slower. Monocyte chemotactic protein-1 (MCP-1) is an early inflammatory marker and increases before complications in severe AP. We conducted a cohort study to evaluate these markers as predictors for severe AP. Method: 140 patients with AP were included, retrospectively grouped as severe or mild by the Atlanta classification. CAPAP, MCP-1 and aCAP were analyzed in admission samples. Receiver operating characteristic curves determined high vs. low levels. Results: The levels of all markers were significantly higher in patients with severe disease. High levels of serum MCP-1 was associated with a high risk of developing severe AP (OR 40.8; 95% CI 8.5-195). High ORs were also seen for urine MCP-1 (OR 7.3; 95% CI 2.2-24.3), serum CAPAP (OR 5.4; 95% CI 1.6-17.7), urine CAPAP (OR 4.8; 95% CI 1.6-14.2), and serum aCAP (OR 3.7; 95% CI 1.2-11.3). Conclusion: Serum MCP-1 at admission was strongly associated with development of severe AP. MCP-1 in urine, CAPAP in serum and urine and aCAP may also be useful for predicting severe AP. Copyright (c) 2008 S. Karger AG, Basel and IAP.
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| 56. |
- Regnér, Sara, et al.
(författare)
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Nya nationella riktlinjer för handläggning av akut pankreatit
- 2021
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Ingår i: Läkartidningen. - 0023-7205. ; 118
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Tidskriftsartikel (refereegranskat)abstract
- This is a short report of the recently published Swedish guidelines for acute pancreatitis, which are based on international guidelines as well as original publications. The report covers diagnosis, classification, treatment and follow up for patients with acute pancreatitis. Early rehydration and goal-based fluid therapy is recommended as well as oral intake of food on demand. Risk factors for development of severe disease and organ failure should be considered already in the emergency unit. Abdominal computer tomography is generally not recommended the first 5-7 days from onset of symptoms. Antibiotic therapy is only recommended when there is suspicion of or a confirmed infection. If intervention is needed for patients with moderate or severe disease a minimal-invasive step-up approach is recommended. Endoscopic Retrograde Cholangiography is generally not recommended as a treatment in the acute phase of the disease. Identification and treatment of the etiology causing acute pancreatitis is essential to prevent new episodes of the disease.
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| 57. |
- Regnér, Sara, et al.
(författare)
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Nya riktlinjer för kronisk pankreatit
- 2020
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Ingår i: Lakartidningen. - 0023-7205. ; 117
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Patients with chronic pancreatitis have an impaired quality of life and are at risk for several long-term complications. It is important to diagnose and treat these patients to minimize the effects of the disease. Clinical manifestations of chronic pancreatitis include a wide range of symptoms and patients are managed differenth between medical centers. In recent years, there have been improvements in knowledge about treatment and management of patients with chronic pancreatitis. This is a short report of the recently published Swedish guidelines for chronic pancreatitis, which are based on international guidelines as well as original publications and are related to the Swedish healthcare system.
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| 58. |
- Regnér, Sara
(författare)
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Protease Activation and Inflammation in Acute Pancreatitis
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Approximately 10—20 % of patients with acute pancreatitis (AP) develop a severe disease with high mortality and morbidity. Activation of pancreatic proteases, the inflammatory response and impaired pancreatic circulation are pathophysiological events that are important in order for the disease to develop. There is no specific treatment for severe AP, and no useful marker for predicting the severity of the disease upon admission to the hospital. In this thesis, markers of early pathophysiological events in AP are investigated, with emphasis on protease activation and inflammation. ProCarboxypeptidase B (proCAP) is a pancreatic proenzyme which, particularly in severe AP, is activated by trypsin thereby forming Carboxypeptidase B (aCAP ) and the activation peptide of proCarboxypeptidase B (CAPAP). An ELISA method for measurement of serum aCAP in patients with AP was developed, and aCAP was shown to inhibit fibrinolysis in vitro. This may contribute to formation of necrosis in AP. The prediction of severity and pathophysiology was studied in patients with mild (n=124) and severe (n=16) AP. Markers of protease activation (aCAP, CAPAP) and inflammation (Monocyte Chemoattractant protein-1 (MCP-1) and CRP) were found to be elevated within 24 hours in patients with severe AP. Protease activation decreased after 48 hours, yet inflammation persisted for a longer period of time. Markers of pancreatic leakage (proCAP) decreased with time without differences in patients with mild and severe AP. MCP-1 exhibited a good capacity at predicting severe AP upon hospital admission. CAPAP and aCAP may also be useful in predicting the degree of severity.
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| 59. |
- Regnér, Sara, et al.
(författare)
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Protease activation, pancreatic leakage, and inflammation in acute pancreatitis: differences between mild and severe cases and changes over the first three days.
- 2008
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Ingår i: Pancreatology. - : Elsevier BV. - 1424-3903. ; 8:6, s. 600-607
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: The pathophysiology of acute pancreatitis (AP) may be studied using markers of protease activation (active carboxypeptidase B (aCAP), the activation peptide of carboxypeptidase B (CAPAP)), leakage of pancreatic enzymes (trypsinogen-2, procarboxypeptidase B (proCAP), amylase), and inflammation (monocyte chemoattractant protein-1 (MCP-1), CRP). METHODS: This prospective study included 140 cases of AP. Mild (n = 124) and severe (n = 16) cases were compared with respect to serum levels of trypsinogen-2, proCAP, amylase, aCAP, CAPAP (serum/urine), MCP-1 (serum/urine) and CRP on days 1, 2 and 3 from onset of symptoms. All patients with information on all 3 days were included in a time-course analysis (n = 44-55, except amylase: n = 27). RESULTS: High levels in severe versus mild cases were seen for trypsinogen-2, CAPAP in serum and urine, and MCP-1 in serum on days 1-3. No differences were seen for proCAP, amylase and aCAP. MCP-1 in urine was significantly elevated on day 1-2, and CRP on day 2-3. CAPAP and MCP-1 levels peaked early and stayed elevated for 48 h in serum. CONCLUSION: Protease activation and inflammation are early events in AP, with high levels of these markers within 24 h. Protease activation declines after 48 h, whereas inflammation is present for a longer time.
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| 60. |
- Sanikini, Harinakshi, et al.
(författare)
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Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite : Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
- 2020
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 146:4, s. 929-942
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Tidskriftsartikel (refereegranskat)abstract
- Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m2: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.
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