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ABSTRACT: BACKGROUND: Portal venous system thrombosis (PVST) is a rare, potentially fatal complication after pancreatic resection. The aim of this study was to assess the incidence, presenting symptoms, management, and treatment of PVST in a large cohort of patients. METHODS: Prospectively collected data on patients undergoing pancreatic resection between 1997 and 2009 were reviewed retrospectively. Preoperative and postoperative imaging were analyzed for the presence or absence of venous thrombi. All patients received standard thromboprophylaxis with low-molecular-weight heparin (LMWH). RESULTS: Of 516 pancreatic resections performed, 18 (3.5 %) were complicated by PVST. The most common clinical presentations were abdominal pain (n = 9) and ascites (n = 5) but never any alarm symptoms. Other symptoms were vague and nonspecific (e.g., weight loss, fatigue, fever). Total pancreatectomy was a risk factor compared to hemipancreatectomy (p < 0.01), whereas the underlying disease per se did not make any difference. The median interval between surgery and diagnosis of PVST was 105 days (range 1-1,440 days). PVST was at least a contributing factor in the postoperative deaths of two patients. LMWH therapy did not significantly affect survival. CONCLUSIONS: PVST remains a relatively infrequent complication after pancreatic resection. Because accurate diagnosis and timely intervention may reduce morbidity and mortality, the possibility of PVST should be considered in patients presenting with vague symptoms. Whether anticoagulant treatment is needed is still not clear; there were no obvious differences in outcome between treated and untreated patients.
World Journal of Surgery 09/2012; · 2.36 Impact Factor
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ABSTRACT: To determine whether prophylactic pancreatic duct stenting reduces pancreatic fistula (PF) formation after distal pancreatectomy (DP).
PF causes major morbidity after DP. Transpapillary pancreatic stenting has been proposed to be beneficial in treating established PF and also, prophylactically, to reduce the risk for PF after DP.
Patients scheduled for DP during October 2006 to December 2010 were assessed and, if eligible, randomized to DP without (DP) or with stenting before transection of the neck of the gland (DP + stent). DP procedure was standardized and the follow-up period included the first 30 postoperative days. The outcomes were assessed according to the intention to treat analysis principle.
: Sixty-four patients were assessed and 58 were randomized to either DP (n = 29) or DP + stent (n = 29). Mean ± SD operation time for DP was 218.8 ± 94.1 compared to 283.3 ± 131.9 for DP + stent (P = 0.052). Clinically significant PF (ISGPF [The International Study Group on Pancreatic Fistula] classification Grade B or C) occurred in 6 DP (22.2%) and 11 (42.3%) DP + stent patients (odds ratio: 2.57, 95% confidence interval 0.78-8.48; P = 0.122). The mean hospital stay for patients without stent was 13.4 ± 6.4 days compared to 19.4 ± 14.4 days for those provided with a pancreatic stent (P = 0.071).
The results from this trial show that prophylactic pancreatic stenting does not reduce PF when performing a standardized resection of the body and tail of the pancreas. The trial was registered at clinicaltrials.gov NCT00500968.
Annals of surgery 06/2012; 255(6):1032-6. · 7.90 Impact Factor
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ABSTRACT: To compare respiratory-triggered, free-breathing, and breath-hold DWI techniques regarding (1) image quality, and (2) signal intensity (SI) and ADC measurements in pancreatic ductal adenocarcinoma (PDAC).
Fifteen patients with histopathologically proven PDAC underwent DWI prospectively at 1.5 T (b = 0, 50, 300, 600 and 1,000 s/mm(2)) with the three techniques. Two radiologists, independently and blindly, assigned total image quality scores [sum of rating diffusion images (lesion detection, anatomy, presence of artefacts) and ADC maps (lesion characterisation, overall image quality)] per technique and ranked them. The lesion SI, signal-to-noise ratio, mean ADC and coefficient of variation (CV) were compared.
Total image quality scores for respiratory-triggered, free-breathing and breath-hold techniques were 17.9, 16.5 and 17.1 respectively (respiratory-triggered was significantly higher than free-breathing but not breath-hold). The respiratory-triggered technique had a significantly higher ranking. Lesion SI on all b-values and signal-to-noise ratio on b300 and b600 were significantly higher for the respiratory-triggered technique. For respiratory-triggered, free-breathing and breath-hold techniques the mean ADCs were 1.201, 1.132 and 1.253 × 10(-3) mm(2)/s, and mean CVs were 8.9, 10.8 and 14.1 % respectively (respiratory-triggered and free-breathing techniques had a significantly lower mean CV than the breath-hold technique).
In both analyses, respiratory-triggered DWI showed superiority and seems the optimal DWI technique for demonstrating PDAC. KEY POINTS : • Diffusion-weighted magnetic resonance imaging is increasingly used to detect pancreatic cancer • Images are acquired using various breathing techniques and multiple b-values • Breathing techniques used: respiratory-triggering, free-breathing and breath-hold • Respiratory-triggering seems the optimal breathing technique for demonstrating pancreatic cancer.
European Radiology 05/2012; 22(10):2186-92. · 3.22 Impact Factor
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ABSTRACT: The outcome of treatment for patients with chronic pancreatitis may be improved by multidisciplinary management.
To study patients with chronic pancreatitis, especially regarding alcohol use, within a multi disciplinary program.
Prospective assessment at baseline and follow-up of alcohol use disorders using DSM-IV criteria, AUDIT score, interview-based quantification of alcohol intake and the biomarker for alcohol use s-CDT in patients referred because of chronic pancreatitis together with retrospective classification with the M-ANNHEIM risk factor analysis and severity scoring for chronic pancreatitis.
Sixty patients (95%) of 63 consecutively included patients were classified as having chronic pancreatitis. Forty-four of these (73%) were available for follow-up evaluation, which took place after a minimum of 1 year (median 3 years). Alcohol consumption decreased at follow-up and no patients had ongoing alcohol dependence (P<0.001) as compared to 10 (23%) at initial evaluation. Patients with harmful alcohol use (AUDIT score ≥8 points) and pathological s-CDT had a reduction in both parameters (P=0.004 and P=0.060, respectively). Pain score according to M-ANNHEIM was unchanged, whereas use of analgesics decreased (P=0.005).
This feasibility study of patients with chronic pancreatitis demonstrated that multidisciplinary management seems to give a positive and sustainable effect on alcohol abuse and may be a useful concept for optimal classification, selection and treatment of patients with chronic pancreatitis.
JOP: Journal of the pancreas 01/2012; 13(6):654-9.
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Gustaf Christoffersson,
Johanna Henriksnäs,
Lars Johansson,
Charlotte Rolny,
Håkan Ahlström,
José Caballero-Corbalan, Ralf Segersvärd,
Johan Permert,
Olle Korsgren,
Per-Ola Carlsson,
Mia Phillipson
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ABSTRACT: Curing type 1 diabetes by transplanting pancreatic islets into the liver is associated with poor long-term outcome and graft failure at least partly due to inadequate graft revascularization. The aim of the current study was to evaluate striated muscle as a potential angiogenic site for islet transplantation.
The current study presents a new experimental model that is found to be applicable to clinical islet transplantation. Islets were implanted into striated muscle and intraislet vascular density and blood flow were visualized with intravital and confocal microscopy in mice and by magnetic resonance imaging in three autotransplanted pancreatectomized patients. Mice were rendered neutropenic by repeated injections of Gr-1 antibody, and diabetes was induced by alloxan treatment.
Contrary to liver-engrafted islets, islets transplanted to mouse muscle were revascularized with vessel densities and blood flow entirely comparable with those of islets within intact pancreas. Initiation of islet revascularization at the muscular site was dependent on neutrophils, and the function of islets transplanted to muscle was proven by curing diabetic mice. The experimental data were confirmed in autotransplanted patients where higher plasma volumes were measured in islets engrafted in forearm muscle compared with adjacent muscle tissue through high-resolution magnetic resonance imaging.
This study presents a novel paradigm in islet transplantation whereby recruited neutrophils are crucial for the functionally restored intraislet blood perfusion following transplantation to striated muscle under experimental and clinical situations.
Diabetes 10/2010; 59(10):2569-78. · 8.29 Impact Factor
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ABSTRACT: Resection of the body and tail of the pancreas (distal pancreatectomy) is associated with high postoperative morbidity, most of which is due to leakage from the pancreatic transection surface.
The aim of the current study was to analyze factors which may affect the risk of pancreatic fistula formation.
All consecutive distal pancreatectomies prospectively registered in our hospital database from 1999 to 2007 were included. Clinically relevant pancreatic fistula grades B and C, defined according to the International Study Group on Pancreatic Fistula (ISGPF) definition were assessed.
The impact of patient, tumor, surgery, and radiology-related factors on the risk of pancreatic fistula formation were assessed by univariate and multivariate analyses.
A distal pancreatectomy was performed in 51 patients (median age: 59 years; range: 26-76 years), 22 of whom had malignant and 29 benign or premalignant disease. Pancreatic fistulas were diagnosed in 17 (33.3%) of the patients. An additional three patients had a local abscess without apparent but assumed pancreatic leakage. Multivariate analysis showed that pancreatic fistulas occurred more frequently after hand suturing of the transection area versus the use of a stapler (69.2% vs. 21.1%; OR: 40.4, 95% CI: 3.36-486; P=0.004) and a large volume of the pancreatic remnant (greater, or equal to, 34 cm3) increased the subsequent risk of pancreatic fistula (57.1% vs. 20.8%; OR: 6.14, 95% CI: 1.14-39.0; P=0.035).
Development of pancreatic fistula after distal pancreatectomy remains a challenge. The volume of the remaining pancreas and the technique of closure of the transected pancreas were found to affect this risk, thus allowing future preventive measures to be explored and evaluated in clinical trials.
JOP: Journal of the pancreas 01/2010; 11(5):439-43.
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ABSTRACT: Obesity is a negative prognostic factor in patients with critical illnesses such as acute pancreatitis (AP). The outcome of AP is determined by the severity of systemic inflammation and organ dysfunction. In a previous study, we found that AP caused more deaths in obese rats than in lean rats. In the present study, we examined whether the effect of obesity on rats with AP is associated with distinct alterations in inflammatory cytokine expression in organs involved in AP.
AP was induced in lean and obese Zucker rats by pancreatic infusion of taurocholic acid. All survivors were killed 8 h later. Gene transcripts for two proinflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha)) and two anti-inflammatory cytokines (IL-10 and pancreatitis-associated protein (PAP)) were determined in the pancreas, liver, and lungs by quantitative real-time polymerase chain reaction. The severity of AP was assessed by means of histology and serology.
Obese AP rats had higher TNF-alpha mRNA in all organs examined, lower IL-10 and IL-6 mRNA in the pancreas, and lower PAP mRNA in the liver, compared to lean AP rats. Lean and obese AP rats had similar pancreatic lesions as assessed by histology. However, steatohepatitis and increased serum alanine amino transferase levels, which are indications of hepatic injury, were present in obese but not lean AP rats.
Our findings suggest that altered inflammatory cytokine expression and increased vulnerability in the liver underlie the detrimental influence of obesity on AP.
Obesity 02/2008; 16(1):23-8. · 4.28 Impact Factor
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ABSTRACT: Intratumoral hypoxia and paracrine insulin stimulate the expression of hypoxia inducible factor-1alpha (HIF-1alpha) in pancreatic cancer cells. In the present studies, we investigated whether insulin-induced HIF-1alpha expression is a prerequisite for insulin to induce other trophic effects in MiaPaCa2 human pancreatic cancer cells and whether inhibition of HIF-1alpha expression would decrease tumor glycolysis and improve host energy homeostasis. We found that hypoxia was a prerequisite for induction of HIF-1alpha mRNA expression by insulin in MiaPaCa2 cells. Under hypoxic conditions, insulin stimulated glycolysis, cell proliferation, and the secretion of vascular endothelial growth factor in regular MiaPaCa2 cells but not in a MiaPaCa2 variant (si-MiaPaCa2) that expressed specific short interfering RNA for HIF-1alpha and therefore lacked HIF-1alpha protein. This suggests that HIF-1alpha expression is required for insulin to induce other trophic effects. When si-MiaPaCa2 cells were transplanted into the pancreas of athymic mice, they were less tumorigenic and expressed less hexokinase than regular MiaPaCa2 cells. Body weight gain was attenuated in mice hosting tumors composed of regular MiaPaCa2 but not si-MiaPaCa2 cells. These results suggest that an interaction between insulin and HIF-1alpha helps sustain pancreatic cancer cells and disturbs host energy homeostasis.
American Journal Of Pathology 03/2007; 170(2):469-77. · 4.89 Impact Factor
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ABSTRACT: Uncoupling-protein 2 (UCP2) is a mitochondrial protein that appears to be involved in cellular oxidant defense and in the regulation of oncotic cell death, both of which are important features of acute pancreatitis. However, UCP2 expression in acute pancreatitis has not been previously reported. In the current experiments, pancreatic gene expression was studied by real-time reverse-transcription/polymerase chain reaction and Northern blots. Two models of acute experimental pancreatitis were investigated: cerulein-induced pancreatitis in mice at two different time points and taurocholate-induced pancreatitis in rats at two degrees of severity. After cerulein administration, acinar injury and leukocyte infiltration was significantly higher at 24 h compared with 12 h after the first injection of cerulein (P<0.05, P<0.005, respectively). UCP2 mRNA was unchanged at 12 h but was nearly 12-fold greater than control levels after 24 h (P<0.001). UCP2 gene expression correlated with acinar injury (r=0.69; P<0.001). By 72 h after taurocholate administration, the severe group had more necrosis than the mild group (P<0.005). Pancreatic UCP2 mRNA was increased fourfold in the severe group compared with controls (P<0.01). UCP2 expression correlated with parenchymal necrosis (r=0.61; P<0.01). Thus, pancreatic UCP2 mRNA increased in two models of acute pancreatitis. The increase in UCP2 gene expression was correlated with the severity of the disease. Up-regulation of UCP2 in the pancreas may be a protective response to oxidative stress, but this increase may also have a negative influence on cellular energy metabolism. Therefore, acinar UCP2 may be an important modifier of the severity of acute pancreatitis.
Cell and Tissue Research 05/2005; 320(2):251-8. · 3.11 Impact Factor
