Publications by authors named "Truls Hauge"

34 Publications

One year comprehensive prospective follow-up of achalasia patients after peroral endoscopic myotomy.

Ann Med 2021 12;53(1):2225-2233

Department of Gastroenterology, Oslo University Hospital, Oslo, Norway.

Background And Aims: Peroral endoscopic myotomy (POEM) is an established therapy for achalasia, but outcome evaluation has often been limited to Eckardt score (ES). The present study was aimed to improve knowledge about outcome evaluation and predictive outcome factors by performing a comprehensive objective evaluation of achalasia patients treated by POEM.

Methods: This single centre prospective study reports outcome data 12 months after POEM in treatment-naive achalasia patients. A predefined follow-up protocol included ES, high resolution manometry, 24-h pH measurement, upper endoscopy and timed barium esophagogram (TBE). Univariate and multivariate regression analyses were performed to analyze association between post-POEM variables and identify predictive factors for objective outcome.

Results: Fifty patients were included with a drop-out rate of <5%. ES, lower oesophageal sphincter pressures, TBE heights and maximal oesophageal diameter were all reduced after POEM ( < .001), and 28% (13/47) of the patients had a positive 24-h pH registration. An oesophageal diameter >3 cm after POEM was associated with treatment failure assessed by ES ( = .04) and TBE ( = .03). Advanced achalasia stage ( = .02) and long symptom duration ( = .04) were identified as independent predictive factors for poor outcome assessed by TBE.

Conclusions: The present study confirms that POEM is an efficient therapy for achalasia. The comprehensive objective evaluation after POEM demonstrates that long symptom duration and major changes in oesophageal anatomy at diagnosis imply poor treatment outcome, and a post-POEM dilated oesophagus is associated with treatment failure.Key messagesPeroral endoscopic myotomy (POEM) is established as a safe and effective therapy for achalasia.Timed barium esophagogram offers objective variables that are valuable in treatment response evaluation. Advanced achalasia stage and long symptom duration are predictive factors for poor objective treatment response after POEM.
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December 2021

Aetiological risk factors are associated with distinct imaging findings in patients with chronic pancreatitis: A study of 959 cases from the Scandinavian Baltic Pancreatic Club (SBPC) imaging database.

Pancreatology 2021 Jun 3;21(4):688-697. Epub 2021 Mar 3.

Department of Radiology, Aalborg University Hospital, Aalborg, Denmark.

Objectives: The relation between aetiology and structural changes of the pancreas in patients with chronic pancreatitis (CP) is not fully understood. Earlier studies are limited by focusing on selected factors in studies of limited sample size. We aimed to use a large dataset to explore associations between aetiology and pancreatic morphology in CP.

Methods: Subjects with definite or probable CP according to the M-ANNHEIM diagnostic criteria were included in this multicentre cross-sectional observational study and assessed using a standardized and validated CP imaging system. We performed multivariate logistic regression to analyse if aetiological factors adjusted for covariates were independently associated with morphological pancreatic features.

Results: We included 959 patients (66% males). Mean (SD) age was 55 (14) years. Pancreatic structural changes were found in 94% of the subjects: 67% had calcifications, 59% main pancreatic duct dilatation, 33% pseudo-cysts and 22% pancreatic atrophy. Alcohol abuse was independently associated with pancreatic calcifications (odds ratio (OR, [95% CI]); 1.61, [1.09, 2.37]) and focal acute pancreatitis (OR; 2.13, [1.27, 3.56]), whereas smoking was independently associated with more severe calcifications (OR; 2.09, [1.34, 3.27]) and involvement of the whole gland (OR; 2.29, [1.61, 3.28]). Disease duration was positively associated with calcifications (OR; (per year) 1.05 [1.02, 1.08]) and pancreatic atrophy (OR; 1.05 [1.02, 1.08]) and negatively associated with focal acute pancreatitis (OR 0.91, [0.87, 0.95] and pseudo cysts (OR; 0.96, [0.93, 0.98]).

Conclusion: In this large-scale study, etiological risk factors and disease duration in CP were independently associated with specific structural pancreatic imaging changes.
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June 2021

Transpancreatic biliary sphincterotomy versus double guidewire in difficult biliary cannulation: a randomized controlled trial.

Endoscopy 2021 10 13;53(10):1011-1019. Epub 2021 Jan 13.

Division of Digestive Surgery and Urology, Turku University Hospital and University of Turku, Turku, Finland.

Background: Difficult biliary cannulation in endoscopic retrograde cholangiopancreatography (ERCP) increases the risk of post-ERCP pancreatitis (PEP). The purpose of this prospective, randomized, multicenter study was to compare two advanced rescue methods, transpancreatic biliary sphincterotomy (TPBS) and a double-guidewire (DGW) technique, in difficult common bile duct (CBD) cannulation.

Methods: Patients with native papilla and planned CBD cannulation were recruited at eight Scandinavian hospitals. An experienced endoscopist attempted CBD cannulation with wire-guided cannulation. If the procedure fulfilled the definition of difficult cannulation and a guidewire entered the pancreatic duct, randomization to either TPBS or to DGW was performed. If the randomized method failed, any method available was performed. The primary end point was the frequency of PEP and the secondary end points included successful cannulation with the randomized method.

Results: In total, 1190 patients were recruited and 203 (17.1 %) were randomized according to the study protocol (TPBS 104 and DGW 99). PEP developed in 14/104 patients (13.5 %) in the TPBS group and 16/99 patients (16.2 %) in the DGW group ( = 0.69). No difference existed in PEP severity between the groups. The rate of successful deep biliary cannulation was significantly higher with TPBS (84.6 % [88/104]) than with DGW (69.7 % [69/99];  = 0.01).

Conclusions: In difficult biliary cannulation, there was no difference in PEP rate between TPBS and DGW techniques. TPBS is a good alternative in cases of difficult cannulation when the guidewire is in the pancreatic duct.
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October 2021

Pain and aetiological risk factors determine quality of life in patients with chronic pancreatitis, but a brick in the puzzle is missing.

Pancreatology 2020 Oct 10;20(7):1347-1353. Epub 2020 Sep 10.

Centre for Pancreatic Diseases, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; Clinical Institute, Aalborg University, Aalborg, Denmark.

Background And Objectives: Chronic pancreatitis (CP) is a debilitating fibro-inflammatory disease with a profound impact on patients' quality of life (QOL). We investigated determinants of QOL in a large cohort of CP patients.

Methods: This was a multicentre study including 517 patients with CP. All patients fulfilled the EORTC QLQ-C30 questionnaire. Questionnaire responses were compared to results obtained from a general reference population (n = 11,343). Demographic characteristics, risk factors (smoking and alcohol consumption), pain symptoms, disease phenotype (complications) and treatments were recorded. A multivariable regression model was used to identify factors independently associated with QOL scores.

Results: Included patients had a mean age of 56.3 ± 12.8 years, 355 (69%) were men and 309 (60%) had alcohol aetiology. Compared to the reference population, patients with CP had lower global health status (50.5 vs. 66.1; p < 0.001) as well as reduced scores for all functional scales (all p < 0.001). Additionally, CP patients reported a higher burden for all symptom items, with pain being the most prominent complaint (all p < 0.001). Constant pain (coefficient -11.3; p = 0.02), opioid based pain treatment (coefficient -19.7; p < 0.001) and alcoholic aetiology (coefficient -5.1; p = 0.03) were independently associated with lowered global health status. The final multivariable model explained 18% of the variance in global health status.

Conclusions: Patients with CP have significantly lower QOL compared to a population-based reference population. Factors independently associated with a lowered QOL are constant pain, opioid based pain treatment and alcohol aetiology. However, these factors only explain a fraction of QOL and additional factors need identification.
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October 2020

Outcome after endoscopic treatment for dysplasia and superficial esophageal cancer - a cohort study.

Scand J Gastroenterol 2020 Sep 4;55(9):1132-1138. Epub 2020 Aug 4.

Department of Pediatric and Gastrointestinal Surgery, Oslo University Hospital, Oslo, Norway.

Background: Dysplasia and superficial esophageal cancer should initially be treated endoscopically. Little is known about post-procedural health-related quality of life (HRQL). The aim of this study was to present our results with endoscopic treatment and post-procedural HRQL.

Materials And Methods: From June 2014 to December 2018, all patients treated with endoscopic mucosal resection (EMR) and/or radiofrequency ablation (RFA) for low-grade dysplasia (LGD), high-grade dysplasia (HGD), T1a and a minority of patients with T1b at Oslo University Hospital were prospectively included. In June 2019, all patients alive were scored according to the Ogilvie dysphagia score as well as the QLQ-C30 and QLQ-OG25 for assessment of HRQL.

Results: Eighty-six patients were treated out of whom 22 (26%) had LGD, 44 (51%) HGD, 13 (15%) T1a, and six patients (7%) T1b. Histology revealed adenocarcinoma in 18 (21%) and squamous cell carcinoma in one (1%), respectively. The mean follow-up was 22.9 months. Tumor regression or downstaging was archived in 78% of the patients with LGD, 66% of patients with HGD and in 89% of patients with T1a/b. Five patients (6%) had esophagectomy. There were few and no serious complications. The 90-days mortality was 1%. Fifty-two patients (88%) experienced no dysphagia (Ogilvie score 0). There was no difference in 11 out of the 15 variables in QLQ-C30 when compared to a non-cancerous reference population.

Conclusions: Endoscopic treatment is safe and efficient for treatment of dysplasia and superficial esophageal cancer. The two-years post-procedural level of HRQL and dysphagia was satisfactory.
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September 2020

Patient reported exposure to smoking and alcohol abuse are associated with pain and other complications in patients with chronic pancreatitis.

Pancreatology 2020 Jul 11;20(5):844-851. Epub 2020 May 11.

Department of Clinical Medicine, University of Bergen, Bergen, Norway; Medical Department, Haukeland University Hospital, Bergen, Norway.

Background/objectives: Smoking and alcohol abuse are established risk factors for chronic pancreatitis (CP). Few studies have examined how exposure to smoking and alcohol abuse act as risk factors for complications in CP. Our aim was to examine associations between patient reported exposure to smoking and alcohol abuse and complications in CP in a large cohort of patients from the Scandinavian and Baltic countries.

Methods: We retrieved data on demographics, CP related complications and patients' histories of exposure to smoking and alcohol abuse from the Scandinavian Baltic Pancreatic Club database. Associations were investigated by univariate and multivariate logistic regression analyses. Results are presented as odds ratios (OR) with 95% confidence intervals.

Results: A complete history of smoking and alcohol exposure was available for 932 patients. In multivariate regression analyses, the presence of pain and exocrine pancreatic insufficiency were both significantly associated with history of smoking (OR 1.94 (1.40-2.68), p < 0.001 and OR 1.89 (1.36-2.62), p < 0.001, respectively) and alcohol abuse (OR 1.66 (1.21-2.26), p = 0.001 and 1.55 (1.14-2.11), p = 0.005, respectively). Smoking was associated with calcifications (OR 2.89 (2.09-3.96), p < 0.001), moderate to severe ductal changes (OR 1.42 (1.05-1.92), p = 0.02), and underweight (OR 4.73 (2.23-10.02), p < 0.001). History of alcohol abuse was associated with pseudocysts (OR 1.38 (1.00-1.90) p = 0.05) and diabetes mellitus (OR 1.44 (1.03-2.01), p = 0.03). There were significantly increased odds-ratios for several complications with increasing exposure to smoking and alcohol abuse.

Conclusion: Smoking and alcohol abuse are both independently associated with development of complications in patients with CP. There seems to be a dose-dependent relationship between smoking and alcohol abuse and complications in CP.
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July 2020

Multiple risk factors for diabetes mellitus in patients with chronic pancreatitis: A multicentre study of 1117 cases.

United European Gastroenterol J 2020 05 17;8(4):453-461. Epub 2020 Jan 17.

Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.

Background: Diabetes mellitus is a common complication of chronic pancreatitis. It is traditionally considered to develop as a consequence of beta cell loss, but there might be additional factors. Recent studies have highlighted the importance of type 2 diabetes-related risk factors in this context and population-based studies show increased risk of diabetes following acute pancreatitis. The aim of this study was to explore multiple risk factors for diabetes in patients with chronic pancreatitis.

Methods: We conducted a multicentre, cross-sectional study of patients with definitive chronic pancreatitis according to the M-ANNHEIM criteria. We used multivariable logistic regression models to determine risk factors independently associated with diabetes.

Results: The study included 1117 patients of whom 457 (40.9 %) had diabetes. The mean age was 52.8 ± 14.2 years and 67% were men. On multivariate analysis, parameters indicative of beta cell loss (pancreatic calcification, exocrine insufficiency, pancreatic resection) were confirmed as independent risk factors for diabetes (all  ≤ 0.02). In addition, type 2 diabetes-related risk factors (dyslipidaemia and overweight/obesity) were associated with the presence of diabetes (all  ≤ 0.002). Patients with a history of pancreatic fluid collections (indicative of previous attacks of acute pancreatitis) had a marginally increased risk of diabetes ( = 0.07).

Conclusion: In patients with chronic pancreatitis the presence of diabetes is associated with multiple risk factors including type 2 diabetes-related factors. Our observations attest to the understanding of this entity and may have implications for treatment.
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May 2020

Pancreatic calcifications associate with diverse aetiological risk factors in patients with chronic pancreatitis: A multicentre study of 1500 cases.

Pancreatology 2019 Oct 21;19(7):922-928. Epub 2019 Aug 21.

Clinical Institute, Aalborg University, Aalborg, Denmark; Department of Radiology, Aalborg University Hospital, Aalborg, Denmark.

Background: Pancreatic calcifications is a common finding in patients with chronic pancreatitis (CP), but the underlying pathophysiology is incompletely understood. Past studies for risk factors of calcifications have generally been focused on single parameters or limited by small sample sizes. The aim of this study was to explore several patient and disease characteristics and their associations with pancreatic calcifications in a large cohort of CP patients with diverse aetiological risk factors.

Methods: This was a multicentre, cross-sectional study including 1509 patients with CP. Patient and disease characteristics were compared for patients with calcifications (n = 912) vs. without calcifications (n = 597). Multivariable logistic regression was performed to assess the parameters independently associated with calcifications.

Results: The mean age of patients was 53.9 ± 14.5 years and 1006 (67%) were men. The prevalence of calcifications was 60.4% in the overall patient cohort, but highly variable between patients with different aetiological risk factors (range: 2-69%). On multivariate analysis, alcoholic aetiology (OR 1.76 [95% CI, 1.39-2.24]; p < 0.001) and smoking aetiology (OR 1.77 [95% CI, 1.39-2.26], p < 0.001) were positively associated with the presence of calcifications, while an autoimmune aetiology was negatively associated with calcifications (OR 0.15 [95% CI, 0.08-0.27], p < 0.001). Patients with pancreatic calcifications were more likely to have undergone pancreatic duct stenting (OR 1.59 [95%CI, 1.16-2.19], p = 0.004).

Conclusion: The presence of pancreatic calcifications is associated with diverse aetiological risk factors in patients with CP. This observation attest to the understanding of CP as a complex disease and may have implications for disease classification.
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October 2019

Macroscopic appearance of the major duodenal papilla influences bile duct cannulation: a prospective multicenter study by the Scandinavian Association for Digestive Endoscopy Study Group for ERCP.

Gastrointest Endosc 2019 12 18;90(6):957-963. Epub 2019 Jul 18.

Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden.

Background And Aims: Certain appearances of the major duodenal papilla have been claimed to make cannulation more difficult during ERCP. This study uses a validated classification of the endoscopic appearance of the major duodenal papilla to determine if certain types of papilla predispose to difficult cannulation.

Methods: Patients with a naïve papilla scheduled for ERCP were included. The papilla was classified into 1 of 4 papilla types before cannulation started. Time to successful bile duct cannulation, attempts, and number of pancreatic duct passages were recorded. Difficult cannulation was defined as after 5 minutes, 5 attempts, or 2 pancreatic guidewire passages.

Results: A total of 1401 patients were included from 9 different centers in the Nordic countries. The overall frequency of difficult cannulation was 42% (95% confidence interval [CI], 39%-44%). Type 2 small papilla (52%; 95% CI, 45%-59%) and type 3 protruding or pendulous papilla (48%; 95% CI, 42%-53%) were more frequently difficult to cannulate compared with type 1 regular papilla (36%; 95% CI, 33%-40%; both P < .001). If an inexperienced endoscopist started cannulation, the frequency of failed cannulation increased from 1.9% to 6.3% (P < .0001), even though they were replaced by a senior endoscopist after 5 minutes.

Conclusions: The endoscopic appearance of the major duodenal papilla influences bile duct cannulation. Small type 2 and protruding or pendulous type 3 papillae are more frequently difficult to cannulate. In addition, cannulation might even fail more frequently if a beginner starts cannulation. These findings should be taken into consideration when performing studies regarding bile duct cannulation and in training future generations of endoscopists.
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December 2019

Trends in management and outcome of cystic pancreatic lesions - analysis of 322 cases undergoing surgical resection.

Scand J Gastroenterol 2019 Aug 19;54(8):1051-1057. Epub 2019 Jul 19.

Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital , Oslo , Norway.

Several guidelines for the management of cystic pancreatic lesions (CPL) exists. From 2013, Oslo University Hospital adapted the European consensus guidelines (ECG) in the decision-making as to whether patients should be advised to have resection or observation for CPL. The aims of the study were to assess changes over time in the workup and diagnostic accuracy of resected CPL, and the short-term surgical outcome. Preoperative radiological workup, clinicopathological characteristics, and perioperative outcomes were retrospectively reviewed in three consecutive time periods (early: 2004-2008, intermediate: 2009-2012, late: 2013-2016). The rate of concordance between the ECG recommendations for resection (ECG+) or observation (ECG-) and the final histological diagnosis were assessed. A total of 322 consecutive patients underwent resection for CPL (early:  89, intermediate:  108, late:  125). The most common diagnoses were intraductal papillary mucinous neoplasia (IPMN, 36.0%), serous cystic neoplasm (SCN, 23.9%), mucinous cystic neoplasm (10.6%), pseudocyst (9.6%), solid pseudopapillary neoplasm (7.8%), and cystic pancreatic neuroendocrine tumour (5.3%). The proportion of ECG+ CPL undergoing surgery increased significantly (42.7% vs. 60.7% vs. 70.4%,  .001). The relative proportion of patients undergoing resection for SCN decreased (38.2% vs. 21.3% vs. 16.0%), whereas it increased for IPMN (31.5% vs. 30.6% vs. 44.0%). The use of magnetic resonance imaging and endoscopic ultrasound increased. There were no differences in postoperative severe complications (23.0% vs. 23.6%) or 90-day mortality (2.3% vs. 0.8%) between ECG+ and ECG- patients. Several changes in the management of CPL were revealed during time. Adherence to guidelines is important in order to avoid unnecessary surgery for CPL.
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August 2019

Chronic Pancreatitis Is Characterized by Distinct Complication Clusters That Associate With Etiological Risk Factors.

Am J Gastroenterol 2019 04;114(4):656-664

Centre for Pancreatic Diseases, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.

Objectives: Chronic pancreatitis (CP) is characterized by several disease-related complications and multiple etiological risk factors. Past studies of associations between complications and risk factors have mostly been limited to single complications or highly focused on single etiologies. Using an objective data-driven approach (cluster analysis), we characterized complication clusters and their associations with etiological risk factors in a large cohort of patients with CP.

Methods: This was a multicenter, cross-sectional study including 1,071 patients with CP from the Scandinavian and Baltic countries. Complications to CP were classified according to the M-ANNHEIM system, and treelet transform was used to derive complication clusters. Cluster complication frequencies were analyzed for their association with main etiological risk factors (smoking and alcohol).

Results: The mean age of participants was 57 years and 66% were men. Alcohol (55%) and smoking (53%) were the most common etiological risk factors and seen in combination in 36% of patients. Cluster analysis identified 3 distinct complication clusters characterized by inflammation, fibrosis, and pancreatic insufficiencies. An independent association between inflammatory complications and alcoholic etiology was seen (odds ratio [OR] 2.00 [95% CI [confidence interval], 1.38-2.90], P < 0.001), whereas smoking was associated with fibrosis-related complications (OR 2.23 [95% CI, 1.56-2.3.20], P < 0.001) and pancreatic insufficiencies (OR 1.42 [95% CI, 1.00-2.01], P = 0.046).

Discussion: Three distinctive clusters of complications to CP were identified. Their differing associations with alcoholic and smoking etiology indicate distinct underlying disease mechanisms.
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April 2019

Outcome of peroral endoscopic myotomy (POEM) in treatment-naive patients. A systematic review.

Scand J Gastroenterol 2019 Jan 16;54(1):1-7. Epub 2019 Jan 16.

a Department of Gastroenterology , Oslo University Hospital.

Objectives: Achalasia is a primary motility disorder of the esophagus characterized by aperistalsis and failure of lower esophageal sphincter (LES) relaxation. Treatment of achalasia aims at reducing LES pressure. The common treatment modalities are laparoscopic Heller myotomy and pneumatic dilatation, but during the last decade, a promising treatment, per oral endoscopic myotomy (POEM), has been introduced. The aim of the present study was to perform a systematic review of the literature to assess the outcome of POEM in treatment-naive patients.

Materials And Methods: A systematic literature search in PubMed, Embase and Cochrane databases was performed using the terms 'Achalasia AND (POEM OR peroral endoscopic myotomy OR per-oral endoscopic myotomy)'. Inclusion criteria were: original article; English language; n ≥ 20 with ≥90% treatment-naive patients; follow-up ≥3 months; and outcome evaluation of POEM including symptom score and objective tests. Exclusion criteria were: reviews and meta-analyses; pediatric data; duplicates; and articles with overlapping data material.

Results: Of the 1641 articles identified, seven were included. The included studies all reported a short-term clinical success of >90%. Clinical success including post-POEM reflux was mainly estimated by symptom scorings. There were few procedure-related complications.

Conclusions: The studies of treatment-naive patients indicate a high rate of clinical success. Nevertheless, a more systematic and standardized evaluation is recommended to improve the reports on outcome of POEM. The follow-up rate should be high and the evaluation protocol should include both symptom scoring and objective testing with predefined treatment goals.
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January 2019

The effect of corn trypsin inhibitor, anti-tissue factor pathway inhibitor antibodies and phospholipids on microvesicle-associated thrombin generation in patients with pancreatic cancer and healthy controls.

PLoS One 2017 14;12(9):e0184579. Epub 2017 Sep 14.

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Circulating microvesicles (MVs) are suggested to be important contributors to cancer-associated thrombosis due to the presence of surface-bound procoagulant molecules like tissue factor (TF) and phosphatidylserine (PS). Pancreatic cancer is considered to be one of the most prothrombotic malignancies. The aim of this study was to describe the impact of analytical variables on MV-associated thrombin generation in patients with pancreatic cancer and in healthy controls. MVs were isolated from citrated plasma and added to pooled normal plasma (PNP). Thrombin generation was measured by the calibrated automated thrombogram. The impact of corn trypsin inhibitor (CTI), anti-tissue factor pathway inhibitor (TFPI) antibodies and phospholipids was described. Antibodies against TF were used to assess TF-dependency, and MV-bound PS activity was measured with the Zymuphen MP-activity kit. MVs from the pancreatic cancer patients displayed higher thrombin generation and higher PS-activity than MVs from the healthy control group, while TF-dependency was observed in only 1 out of 13 patient samples. Adequate thrombin generation-curves were only achieved when CTI was omitted and anti-TFPI antibodies were added to PNP prepared in low contact-activating tubes. Addition of phospholipids reduced the significant differences between the two groups, and should be omitted. This modified thrombin generation assay could be useful for measurement of procoagulant circulating MVs, allowing the contribution from MVs affecting both the intrinsic and the extrinsic pathway to be measured.
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October 2017

Analysis of lifestyle factors in patients with concomitant chronic pancreatitis and liver cirrhosis.

Pancreatology 2017 Sep - Oct;17(5):698-705. Epub 2017 Jul 31.

Department of Surgery, Technical University of Munich, Munich, Germany.

Background & Objectives: Chronic pancreatitis (CP) and liver cirrhosis (LC) are common gastroenterological disorders but their co-incidence is considered to be rare. This study was designed to identify lifestyle factors that are associated with the development of concomitant LC in patients with CP.

Methods: In a retrospective case-control study between 2000 and 2005 122 patients with both CP and LC and 223 matched control patients with CP and no known liver disease were identified in 11 European university medical centers. Another 24 patients and 48 CP controls were identified in the period between 2006 and 2012.

Results: Alcoholism was most commonly regarded as aetiology for both CP (82.2%; 95% confidence interval (CI): 75.0-88.0%) and LC (79.5%; 95% CI: 72.0-85.7%) as compared to controls with CP only (68.6%; 95% CI: 62.7-74.1%). The preferred type of alcoholic beverage and pattern of alcohol intake were the only significant lifestyle factors in multivariate analysis. Frequency of alcohol intake (p = 0.105) and smoking status (p = 0.099) were not significant in bivariate analysis and dropped out of the multivariate model. Recurrent and chronic pancreatic pain was observed more often in patients with only CP, whereas gallstones were more common in individuals with both chronic disorders.

Conclusions: These findings indicate that certain lifestyle factors might be important for the development of concomitant CP and LC. More studies will be needed to identify additional genetic and environmental factors underlying this association.
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June 2018

Baseline oxidative defense and survival after 5-7 years among elderly stroke patients at nutritional risk: Follow-up of a randomized, nutritional intervention trial.

Clin Nutr 2015 Aug 25;34(4):775-8. Epub 2014 Jul 25.

Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway; Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Norway.

Background & Aims: Patients at nutritional risk are particularly vulnerable to adverse outcomes of acute stroke. We previously found that increased energy- and protein intervention improved short-term survival among stroke patients with the highest baseline antioxidant capacity. We now examined survival of these patients after 5-7 years.

Methods: We studied 165 patients >65 years admitted to hospital for acute stroke and enrolled in a randomized nutritional intervention study in 2005-2007. Cox regression analysis was used to estimate the associations between all-cause mortality (through 2011) and baseline plasma levels of antioxidant markers (glutathione reducing capacity, alpha-tocopherol, vitamin C and total carotenoids).

Results: We found no significant difference (P = 0.86) in survival between the intervention and control group. Among the tested antioxidant markers, plasma levels above the median for total carotenoids were associated with reduced risk of death in the intervention group (adjusted hazard ratio, 0.29; 95% confidence interval, 0.12-0.71).

Conclusions: Hospitalized patients that received enhanced dietary energy- and protein after acute stroke and with baseline plasma total carotenoids above median level, had reduced risk of death after 5-7 years. Further trials testing intervention with diets rich in antioxidants are warranted.
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August 2015

Difficult cannulation as defined by a prospective study of the Scandinavian Association for Digestive Endoscopy (SADE) in 907 ERCPs.

Scand J Gastroenterol 2014 Jun 14;49(6):752-8. Epub 2014 Mar 14.

Department of Gastrointestinal and General Surgery, Helsinki University Central Hospital , Helsinki , Finland.

Background: The definition of a "difficult" cannulation varies considerably in reports of endoscopic retrograde cholangiopancreatography (ERCP).

Aims: To define a difficult cannulation, which translates into higher risk of post-ERCP pancreatitis.

Patients And Methods: Prospective consecutive recording of 907 cannulations in Scandinavian centers done by experienced endoscopists. Inclusion: indication for biliary access in patients with intact papilla. Exclusion: acute non-biliary and chronic pancreatitis at time of procedure.

Results: The primary cannulation succeeded in 74.9%, with median values for time 0.88 min (53 s), with two attempts and with zero pancreatic passages or injections. The overall cannulation success was 97.4% and post-ERCP pancreatitis (PEP) rate was 5.3%. The median time for all successful cannulations was 1.55 min (range 0.02-94.2). If the primary cannulation succeeded, the pancreatitis rate was 2.8%; after secondary methods, it rose to 11.5%. Procedures lasting less than 5 min had a PEP rate of 2.6% versus 11.8% in those lasting longer. With one attempt, the PEP rate was 0.6%, with two 3.1%, with three to four 6.1%, and with five and more 11.9%. With one accidental pancreatic guide-wire passage, the risk of the PEP was 3.7%, and with two passages, it was 13.1%.

Conclusions: If the increasing rate of PEP is taken as defining factor, the wire-guided cannulation of a native papilla can be considered difficult after 5 min, five attempts, and two pancreatic guide-wire passages when any of those limits is exceeded.
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June 2014

Opportunities of improvement in the management of pancreatic and periampullary tumors.

Scand J Gastroenterol 2013 May;48(5):617-25

Department of Gastroenterological Surgery, Division of Cancer, Surgery and Transplantation, Oslo University Hospital (OuS), Oslo, Norway.

Abstract Objective. The first objective of the present study was to identify opportunities of improvement for clinical practice, assessed by local quality indicators, then to analyze possible reasons why we did not reach defined treatment quality measures. The second objective was to characterize patients, considered unresectable according to present criteria, for future arrangement of interventional studies with improved patient selection. Material and methods. Prospective observational cohort study from October 2008 to December 2010 of patients referred to the authors' institution with suspected pancreatic or periampullary neoplasm. Results. Of 330 patients, 135 underwent surgery, 195 did not, 129 due to unresectable malignancies. The rest had benign lesions. Perioperative morbidity rate was 32.6%, mortality 0.7%. Radical resection (R0) was obtained in 23 (41.8%) of 55 patients operated for pancreatic adenocarcinoma and 6.3% underwent reconstructive vascular surgery. Diagnostic failure/delay resulted in unresectable carcinoma, primarily misconceived as serous cystic adenoma in two patients. One resected lesion turned out to be focal autoimmune pancreatitis. One case with misdiagnosed cancer was revised to be a pseudoaneurysm. Palliative treatment was offered to 144 patients with malignant tumors, 62 due to locally advanced disease and all pancreatic adenocarcinomas. Conclusions. Quality improvement opportunities were identified for patient selection and surgical technique: Too few patients underwent reconstructive vascular surgery. The most important quality indicators are those securing resectional, radical (R0) surgery. Altogether 143 patients (57.9%) of those with malignant tumors were found unresectable, most of these patients are eligible for inclusion in future interventional studies with curative and/or palliative intention.
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May 2013

Improved survival and quality of life in patients undergoing R1 pancreatic resection compared to patients with locally advanced unresectable pancreatic adenocarcinoma.

Pancreatology 2013 Mar-Apr;13(2):180-5. Epub 2013 Jan 22.

Department of Cancer, Surgery, and Transplantation, Oslo University Hospital, and Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

Objective: To prospectively record the clinical consequences of R1 resection of pancreatic adenocarcinoma compared to patients with locally advanced tumours not undergoing surgery.

Background: Surgery is the only potentially curative treatment of pancreatic cancer, and postoperative safety is increasing. The rate of R1 resections might also increase unintentionally as surgical procedures with curative goal become more comprehensive, and the clinical outcome requires further prospective evaluation.

Material And Methods: Prospective observational cohort study from October 2008 to December 2010. Outcome after R1 resection (group 1, surgery, n = 32) and conservative palliative chemoradiation/endoscopy (group 2, no surgery, n = 56) is compared with survival and longitudinal patient-reported quality of life (QoL) as endpoints. QoL was assessed by the Edmonton Symptom Assessment System (ESAS).

Results: Demographic characteristics and tumour diameters were similar in both groups: 38.0 (31.3, 49.8) mm in group 1 versus 44.0 (39.6, 49.1) mm in group 2 (p = 0.18). Perioperative morbidity was 25% with no mortality. Disease-specific survival was 18.0 (14.5, 23.8) months in group 1 versus 8.1 (4.8, 10.1) months in group 2 (p < 0.0001). Overall survival was 11 (7.8, 14.4) months. Reduction in fatigue was significantly improved in the surgery group 6, 12, and 19 weeks after baseline, whereas reduction in global health was significantly better in group 2.

Conclusion: Radical removal (R0 resection) is the primary aim of surgery, but also R1 resection seems to improve survival and QoL, compared to outcome in patients with locally advanced tumours not undergoing surgery.
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October 2013

Iatrogenic esophago-tracheal fistula: challenges in diagnosis and management.

World J Gastroenterol 2013 Jan;19(4):594-6

Department of Gastroenterology/Internal Medicine, Innlandet Hospital Trust, 2819 Gjøvik, Norway.

Esophageo-tracheal fistula is a rare condition, and in most cases such fistulas are caused by malignant disease or emergency endotracheal intubation. A case where a wrapped tablet produced a fistula between the esophagus and trachea is described. The patient is a male born in 1938 who swallowed a tablet without unwrapping it. The patient was treated with self-expanding metal stents (SEMS), but closure of the fistula was not achieved. Different examinations and treatment options are discussed. Surgical treatment for this condition has demonstrated considerable mortality and morbidity. In some cases closure of the fistula can be achieved by use of SEMS. Although we advise treatment of such cases with SEMS, in some cases treatment with stents will prove troublesome and the risk/benefit analysis will have to be reevaluated.
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January 2013

Long-term outcome of palliative treatment with self-expanding metal stents for malignant obstructions of the GI tract.

Scand J Gastroenterol 2012 Dec 10;47(12):1505-14. Epub 2012 Oct 10.

Department of Gastroenterology, Oslo University Hospital, Ullevål, Oslo, Norway.

Background: Self-expanding metal stents (SEMS) are commonly used in the palliative treatment of malignant gastrointestinal (GI) obstructions with favorable short-term outcome. Data on long-term outcome are scarce, however.

Aim: To evaluate long-term outcome after palliative stent treatment of malignant GI obstruction.

Method: Between October 2006 and April 2008, nine Norwegian hospitals included patients treated with SEMS for malignant esophageal, gastroduodenal, biliary, and colonic obstructions. Patients were followed for at least 6 months with respect to stent patency, reinterventions, and readmissions.

Results: Stent placement was technically successful in 229 of 231 (99%) and clinically successful after 1 week in 220 of 229 (96%) patients. Long-term follow-up was available for 219 patients. Of those, 72 (33%) needed reinterventions. Stent occlusions or migrations (92%) were the most common reasons. Esophageal stents required reinterventions most frequently (41%), and had a significantly (p = 0.02) shorter patency (median 152 days) compared to other locations (gastroduodenal, 256 days; colon, 276 days; biliary, 460 days). Eighty percent of reinterventions were repeated endoscopic procedures that successfully restored patency. Readmissions were required for 156 (72%) patients. Progression of the underlying cancer was the most common reason, whereas 24% were readmitted due to stent complications.

Conclusions: Long-term outcome after palliative treatment with SEMS for malignant GI and biliary obstruction shows that 70% had a patent stent until death, and that most reobstructions could be solved endoscopically. Hospital readmissions were mainly related to progression of the underlying cancer disease.
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December 2012

Stent treatment of malignant gastric outlet obstruction: the effect on rate of gastric emptying, symptoms, and survival.

Surg Endosc 2012 Oct 27;26(10):2955-60. Epub 2012 Apr 27.

Department of Gastroenterology, Oslo University Hospital, Kirkeveien 166, Ullevål, 0407, Oslo, Norway.

Background: Advanced pancreatic cancer and other malignancies located proximal to the small bowel might cause gastric outlet obstruction (GOO) resulting in nausea, vomiting, dehydration, and malnutrition. Self-expandable metal stents (SEMS) to a large extent have replaced surgical treatment, with gastro-entero-anastomosis as palliative treatment for GOO. The aim of the present study was to evaluate the effect of duodenal stenting on the rate of gastric emptying, symptoms, and survival.

Methods: Patients with endoscopically verified malignant obstruction of the proximal duodenum were included. Gastric emptying rate was measured prior to and within 1 week after stent placement using a meal containing (13)C-octanoic acid as a marker. Symptoms related to GOO were assessed by the patients before and 2 weeks after stent treatment and during the gastric emptying tests. All patients were followed up until death.

Results: In the patients included (n = 17), all studied variables of gastric emptying improved significantly following treatment, and a reduction in self-reported obstructive symptoms was observed. There was no correlation between survival and the rate of gastric emptying before or after, or the change in the rate of emptying.

Conclusion: The present study demonstrated that treatment with SEMS results in improved gastric emptying in most patients with GOO and a corresponding reduction in self-reported obstruction symptoms. However, survival and emptying were not related. The present findings provide further evidence that treatment with stents is an effective palliative treatment in patients with GOO.
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October 2012

How to cannulate? A survey of the Scandinavian Association for Digestive Endoscopy (SADE) in 141 endoscopists.

Scand J Gastroenterol 2012 Jul 19;47(7):861-9. Epub 2012 Apr 19.

Gastrocentrum Kirurgi, Karolinska Universitetssjukhuset, Stockholm, Sweden.

Cannulation of the papilla vateri represents an enigmatic first step in endoscopic retrograde cholangiopancreaticography (ERCP). In light of falling numbers of (diagnostic) ERCP and novel techniques, e.g. short-wire system, we were interested in the approach novice and experienced endoscopist are taking; especially, what makes a papilla difficult to cannulate and how to approach this. We devised a structured online questionnaire, sent to all endoscopists registered with SADE, the Scandinavian Association for Digestive Endoscopy. A total of 141 responded. Of those, 49 were experienced ERCP-endoscopists (>900 ERCPs). The first choice of cannulation is with a sphincterotome and a preinserted wire. Both less experienced and more experienced endoscopists agreed on the criteria to describe a papilla difficult to cannulate and both would choose the needle-knife sphincterotomy (NKS) to get access to the bile duct. The less experienced used more "upward" NKS, whereas the more experienced also used the "downward" NKS technique. This survey provides us with a database allowing now for a more differentiated view on cannulation techniques, success, and outcome in terms of pancreatitis.
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July 2012

Patient-reported outcomes in palliative gastrointestinal stenting: a Norwegian multicenter study.

Surg Endosc 2011 Oct 13;25(10):3162-9. Epub 2011 Apr 13.

Department of Medical Gastroenterology, Oslo University Hospital, Ullevål, Oslo, Norway.

Background: The clinical effect of stent treatment has been evaluated by mainly physicians; only a limited number of prospective studies have used patient-reported outcomes for this purpose. The aim of this work was to study the clinical effect of self-expanding metal stents in treatment of malignant gastrointestinal obstructions, as evaluated by patient-reported outcomes, and compare the rating of the treatment effect by patients and physicians.

Methods: Between November 2006 and April 2008, 273 patients treated with SEMS for malignant GI and biliary obstructions were recruited from nine Norwegian hospitals. Patients and physicians assessed symptoms independently at the time of treatment and after 2 weeks using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire supplemented with specific questions related to obstruction.

Results: A total of 162 patients (99 males; median age = 72 years) completed both assessments and were included in the study. A significant improvement in the mean global health score was observed after 2 weeks (from 9 to 18 on a 0-100 scale, P < 0.03) for all stent locations. Both patients and physicians reported a significant reduction in all obstruction-related symptoms (>20 on the 0-100 scale, P < 0.006) after SEMS treatment. The physicians reported a larger mean improvement in symptoms than did the patients, mainly because they reported more severe symptoms before treatment.

Conclusion: SEMS treatment is effective in relieving symptoms of malignant GI and biliary obstruction, as reported by patients and physicians. The physicians, however, reported a larger reduction in obstructive symptoms than did the patients. A prospective assessment of patient-reported outcomes is important in evaluating SEMS treatment.
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October 2011

Body composition in older acute stroke patients after treatment with individualized, nutritional supplementation while in hospital.

BMC Geriatr 2010 Oct 18;10:75. Epub 2010 Oct 18.

Department of Internal Medicine, Østfold Hospital Trust Fredrikstad, 1603 Fredrikstad, Norway.

Background: Individualized, nutritional support reduced undernutrition among older stroke patients and improved quality of life in our recent randomized, controlled trial. Weight control thus seems to be important after stroke, and methods for monitoring nutritional status need to be simple and non-invasive. Here we aimed to assess if the nutritional intervention altered body composition in men and women in this study cohort, and also to examine the correlation between the methods for assessing body-, fat- and fat-free mass.

Methods: Acute stroke patients > 65 years at nutritional risk were randomized to either individualized, nutritional treatment with energy- and protein rich supplementation (intervention, n = 58) or routine, nutritional care (control, n = 66) while in hospital. Body composition was assessed with anthropometry and bioelectrical impedance. The follow-up period was three months.

Results: During the first week while in hospital, weight loss was smaller in the intervention group compared with the controls (P = 0.013). After three months weight- and fat loss were significant in both men and women. Whereas no significant differences were found in changes in body composition between the male study groups, in the women both weight loss (P = 0.022) and fat loss (P = 0.005) was smaller in the intervention group compared with the controls. A high correlation (r = 0.87) between mid upper arm circumference (MUAC) and body mass index (BMI) was found.

Conclusions: Individualized nutritional support to older stroke patients in hospital was beneficial for maintaining an adequate body mass and body composition the first week and seemed to have a preventive effect on fat loss among women, but not among men after three months. Measurement of MUAC may be used in the assessment of nutritional status when BMI cannot be obtained.

Trial Registration: This trial is registered with, number NCT00163007.
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October 2010

Individual, nutritional support prevents undernutrition, increases muscle strength and improves QoL among elderly at nutritional risk hospitalized for acute stroke: a randomized, controlled trial.

Clin Nutr 2010 Oct 21;29(5):567-73. Epub 2010 Feb 21.

Department of Internal Medicine, Østfold Hospital Trust Fredrikstad, 1603 Fredrikstad, Norway.

Background & Aims: Undernutrition after an acute stroke increases the risk of poor outcome. We wanted to examine the effect of individualized, nutritional support on weight loss and functional outcomes in stroke patients.

Methods: Acute stroke patients at nutritional risk were randomized to either individualized, nutritional care or routine care while in hospital. Patients in the intervention group received an individualized treatment plan aiming to prevent weight loss. In accordance with routine care, the controls did not have such a treatment plan. Patients were reviewed at follow-up after three months. Primary outcome measure was the percentage of patients with weight loss ≥5%. Secondary outcomes measures were quality of life (QoL), handgrip strength and length of hospital stay. This trial is registered with, number NCT00163007.

Results: At follow-up, 20.7% of the intervention group (n = 58) lost ≥5% weight compared with 36.4% in the control group (n = 66) (P = 0.055). The intervention group had a significantly higher increase in QoL score (P = 0.009) and in handgrip strength (P = 0.002). There was no difference in length of hospital stay.

Conclusions: Individualized, nutritional treatment strategy can prevent clinically significant weight loss and improve QoL in elderly acute stroke patients at nutritional risk.
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October 2010

Endoscopic sealing of pancreatic fistulas: four case reports and review of the literature.

Scand J Gastroenterol 2009 ;44(12):1491-6

Department of Gastroenterological Surgery, Oslo University Hospital, Oslo, Norway.

We report four patients with pancreatic fistulas that failed to respond to conservative treatment. The fistulas were closed by endoscopic injection of N-butyl-2-cyanoacrylate (Histoacryl) diluted with an oily contrast agent (Lipiodol). A literature review revealed 32 similar cases in which endoscopic treatment with fibrin sealants (n = 11) or cyanoacrylate (n = 21) was used to close the fistulas. Based on our own experience and the literature review, we conclude that endoscopic sealing of pancreatic fistulas can be performed safely and effectively by experienced endoscopists in a tertiary centre. The procedure seems useful in the management of complicated pancreatic fistulas which do not respond to conservative treatment and may obviate the need for surgery.
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March 2010

Treatment of malignant gastric outlet obstruction with stents: an evaluation of the reported variables for clinical outcome.

BMC Gastroenterol 2009 Jun 17;9:45. Epub 2009 Jun 17.

Department of Gastroenterology, Oslo University Hospital, Ullevaal, Department of Gastroenterology, Kirkeveien 166, N-0407 Oslo, Norway.

Background: Malignant gastric outlet obstruction (GOO) is commonly seen in patients with advanced gastric-, pancreatic-, duodenal, hepatobiliary or metastatic malignancies. Ten to 25% of patients with pancreatic cancer will develop duodenal obstruction during the course of the disease. Duodenal stenting with self-expandable metal stents is an alternative treatment to surgical bypass procedures. Our aim was to review the published literature regarding treatment of malignant GOO with stents to reveal whether the information provided is sufficient to evaluate the clinical effects of this treatment

Methods: A literature search from 2000-2007 was conducted in Pub Med, Embase, and Cochrane library, combining the following search terms: duodenal stent, malignant duodenal obstruction, gastric outlet obstruction, SEMS, and gastroenteroanastomosis. All publications presenting data with > or = 15 patients and only articles written in English were included and a review focusing on the following parameters were conducted: 1) The use of graded scoring systems evaluating clinical success; 2) Assessment of Quality of life (QoL) before and after treatment; 3) Information on stent-patency; 4) The use of objective criteria to evaluate the stent effect.

Results: 41 original papers in English were found; no RCT's. 16 out of 41 studies used some sort of graded scoring system. No studies had objectively evaluated QoL before or after stent treatment, using standardized QoL-questionnaires, 32/41 studies reported on stent patency and 9/41 performed an oral contrast examination after stent placement. Objective quantitative tests of gastric emptying had not been performed.

Conclusion: Available reports do not provide sufficient relevant information of the clinical outcome of duodenal stenting. In future studies, these relevant issues should be addressed to allow improved evaluation of the effect of stent treatment.
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June 2009

Does glyceryl nitrate prevent post-ERCP pancreatitis? A prospective, randomized, double-blind, placebo-controlled multicenter trial.

Gastrointest Endosc 2009 May;69(6):e31-7

Department of Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark.

Objective: Acute pancreatitis is the most dreaded complication of ERCP. Two studies have shown a significant effect of glyceryl nitrate (GN) in preventing post-ERCP pancreatitis (PEP). We wanted to evaluate this promising effect in a larger study with a realistically precalculated incidence of PEP.

Design/patients: A randomized, double-blind, placebo-controlled multicenter study including patients from 14 European centers was performed. A total of 820 patients were entered; 806 were randomized.

Intervention: The active drug was transdermal GN (Discotrine/Minitran, 3M Pharma) 15 mg/24 hours; placebo (PL) was an identical-looking patch applied before ERCP. A total of 401 patients received GN; 405 received PL.

Results: Forty-seven patients had PEP (5.8%), 18 (4.5%) in the GN group and 29 (7.1%) in the PL group. The relative risk reduction of PEP in the GN group of 36% (95% CI, 11%-65%) compared with the PL group was not statistically significant (P = .11). Thirteen had mild pancreatitis (4 in the GN group, 9 in the PL group), 26 had moderate pancreatitis (9 in the GN group, 17 in the PL group), and 8 had severe pancreatitis (5 in the GN group, 3 in the PL group). Headache (P < .001) and hypotension (P = .006) were more common in the GN group. Significant variables predictive of PEP were not having biliary stones extracted; hypotension after ERCP; morphine, propofol, glucagon, and general anesthesia during the procedure; or no sufentanil during the procedure.

Conclusions: The trial showed no statistically significant preventive effect of GN on PEP. Because of a considerable risk of a type II error, an effect of GN may have been overlooked. ( ID: NCT00121901.).
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May 2009

[Nutrition for elderly acute stroke patients].

Tidsskr Nor Laegeforen 2008 Sep;128(17):1946-50

Indremedisinsk avdeling, Sykehuset Østfold Fredrikstad, 1603 Fredrikstad.

Background: Elderly people have an increased risk of malnutrition due to biological and physiological changes and underlying disease. Almost 90% of the stroke patients are older than 65 years, and the consequences of acute stroke may lead to additional nutritional problems. This paper reviews nutritional therapy for stroke patients.

Material And Method: PubMed was searched (non-systematically) for prospective cohort studies of occurrence, diagnostics and consequences of undernutrition in stroke patients. Randomized trials were examined to identify clinical effects of oral protein and energy supplements or tube feeding on nutritional status and intake, functional status, infections, length of stay, quality of life and mortality.

Results: 8-35% of stroke patients are undernourished. Body weight is one of the most important parameters for assessment of nutritional status. Dysphagia occurs in up to 80% of patients with acute stroke and increases the risk of undernutrition, which again leads to prolonged length of stay, reduced functional status and poorer survival. Early nasogastric tube feeding does not increase the risk of pneumonia and may improve survival after six months. Oral supplements lead to a significantly improved nutritional intake in undernourished stroke patients, as well as improved nutritional status and survival in undernourished elderly.

Interpretation: Nutritional treatment can improve the clinical outcome after an acute stroke, provided that there are good procedures for follow-up and monitoring of the treatment.
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September 2008