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Background: Hemorrhage from the pancreatic duct, i.e. hemosuccus pancreaticus (HP), is a rare cause of gastrointestinal bleeding. This potentially life-threatening complication of chronic pancreatitis may pose a significant diagnostic and therapeutic dilemma, especially in patients with silent forms of the disease. Methods: We report a case of a 64-year-old man with no history or symptoms but positive findings of chronic calcifying pancreatitis at computed tomography (CT) scan. Results: The patient presented with repeated episodes of gastrointestinal bleeding requiring transfusion and did not, until later in the disease, develop hyperamylasemia and epigastric pain. Repeated endoscopies could not reveal the source of bleeding. The radiological diagnosis and successful transcatheter embolization of a small splenic pseudoaneurysm were performed during an interval when the patient was asymptomatic and showed no signs of bleeding. Conclusion: We suggest that when HP is suspected, a contrast-enhanced CT angiography with reconstruction of the arteries should be performed regardless of whether the patient shows signs of active bleeding or not.Copyright © 2004 S. Karger AG, Basel and IAP [ABSTRACT FROM AUTHOR]

Background: There are very few data in the current literature regarding the short- and long-term outcome of surgery for pediatric pancreatic tumors (PPT). No data are available on the impact of pancreatic surgery on the children's growth., Methods: This is a retrospective cohort study on a consecutive series of pediatric/adolescent patients who underwent pediatric surgery at Karolinska University Hospital from January 2005 to July 2017., Results: Overall 14 pancreatic operations were performed in 13 patients. The median age was 11.4 years (range 3-15). Six pancreaticoduodenectomies (42.8%), 5 distal pancreatectomies (35.7%), and 3 enucleations (21.5%) were performed. The final histology revealed a solid pseudopapillary tumor in 9 cases (69.2%), neuroblastoma in 1 (7.7%), ganglioneuroma in 1 (7.7%), pancreatoblastoma in 1 (7.7%), and insulinoma in 1 (7.7%). Overall, 3 patients developed post-operative complications (23%). There was no peri-operative mortality. All patients are alive after a median follow-up time of 80 months. Exocrine insufficiency was detected post-operatively in 4 patients (30.7%) Endocrine insufficiency requiring insulin treatment developed in one patient (7.7%). No significant impact on growth was detected in any of the patients after pancreatic resection., Conclusions: In our series, surgery performed for PPTs seems to be safe and effective. The effect of pancreatic surgery on children's growth does not seem to be significant., (Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) is a tumor with an extremely poor prognosis, predominantly as a result of chemotherapy resistance and numerous somatic mutations. Consequently, PDAC is a prime candidate for the use of sequencing to identify causative mutations, facilitating subsequent administration of targeted therapy. In a feasibility study, we retrospectively assessed the therapeutic recommendations of a novel, evidence-based software that analyzes next-generation sequencing (NGS) data using a large panel of pharmacogenomic biomarkers for efficacy and toxicity. Tissue from 14 patients with PDAC was sequenced using NGS with a 620 gene panel. FASTQ files were fed into treatmentmap. The results were compared with chemotherapy in the patients, including all side effects. No changes in therapy were made. Known driver mutations for PDAC were confirmed (e.g. KRAS, TP53). Software analysis revealed positive biomarkers for predicted effective and ineffective treatments in all patients. At least one biomarker associated with increased toxicity could be detected in all patients. Patients had been receiving one of the currently approved chemotherapy agents. In two patients, toxicity could have been correctly predicted by the software analysis. The results suggest that NGS, in combination with an evidence-based software, could be conducted within a 2-week period, thus being feasible for clinical routine. Therapy recommendations were principally off-label use. Based on the predominant KRAS mutations, other drugs were predicted to be ineffective. The pharmacogenomic biomarkers indicative of increased toxicity could be retrospectively linked to reported negative side effects in the respective patients. Finally, the occurrence of somatic and germline mutations in cancer syndrome-associated genes is noteworthy, despite a high frequency of these particular variants in the background population. These results suggest software-analysis of NGS data provides evidence-based information on effective, ineffective and toxic drugs, potentially forming the basis for precision cancer medicine in PDAC., (© 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of pancreatic ductal adenocarcinoma, a deadly disease with a median survival of 24 months for resected tumors and a 5-year survival rate of 6%. After adjuvant chemotherapy, 2 patients with resected pancreatic ductal adenocarcinoma underwent HSCT with HLA-identical sibling donors. Comparable patients who underwent radical surgery, but did not have a donor, served as controls (n=6). Both patients developed humoral and cellular (ie, HLA-A*01:01-restricted) immune responses directed against 2 novel tumor-associated antigens (TAAs), INO80E and UCLH3 after HSCT. Both TAAs were highly expressed in the original tumor tissue suggesting that HSCT promoted a clinically relevant, long-lasting cellular immune response. In contrast to untreated controls, who succumbed to progressive disease, both patients are tumor-free 9 years after diagnosis. Radical surgery combined with HSCT may cure pancreatic adenocarcinoma and change the cellular immune repertoire capable of responding to clinically and biologically relevant TAAs.

Abstract : Cancer patients experience weight loss for a variety of reasons, commencing with the tumor's metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes.

Background: Levodopa-carbidopa intestinal gel (LCIG; Duodopa®) is used for continuous infusion in advanced Parkinson's disease. To achieve optimal effect, the LCIG dose is individually titrated, traditionally conducted during hospitalization in Sweden. However, dose adjustment depends on surrounding conditions, physical activity, and emotional stress, which is why titration at home could be beneficial. Telemedicine (TM) using a video communication system offers alternative titration procedures, allowing LCIG initiation at home., Objective: Study objectives were to show the feasibility of TM for LCIG home titration, evaluate resource use, and assess patient, neurologist, and nurse satisfaction., Methods: Four clinics enrolled 15 patients to observe efficiency and feasibility of TM-based monitoring., Results: Patient median (range) age was 67 (52-73) years and time since diagnosis was 10 (7-23) years. Median time between LCIG initiation and end of TM-assisted titration was 2.8 (2.0-13.8) days. Median time required for home titration by neurologists, nurses, and patients was (hours:minutes) 1 : 14 (0 : 29-1 : 52), 5 : 49 (2 : 46-10 : 3), and 8 : 53 (4 : 11-14 : 11), respectively. Neurologists and nurses considered this to be less time than required for hospital titration. TM allowed patients 92% free time from start to end of titration. Technical problems associated with TM contacts were rare, mostly related to digital link, and quickly resolved. Patients, neurologists, and nurses were satisfied using TM. No serious adverse events were reported; there was one device complaint (tube occlusion)., Conclusions: In this study, TM-assisted LCIG titration at home was resource-efficient, technically feasible, well-accepted and was deemed satisfactory by patients, neurologists, and nurses.

Background and Objective: Endoscopic mucosal dissection (ESD) is a treatment option for oesophagus tumours localized to the mucosa enabling en bloc removal of large lesions. The resulting larger mucosal defects have resulted in an increase in the occurrence of post-treatment strictures. Transplantation of autologous cell sheets, cultured from oral mucosa, has been shown to prevent post-ESD strictures. The aim of the study was to assess the efficacy and safety of cell sheet transplantation after oesophageal ESD in a Western patient population where reflux-associated pre-malignant and malignant conditions predominate., Methods: Patients with Barrett's oesophagus associated high-grade dysplasia or early adenocarcinoma where ESD entailed a resection >3 cm in length and ≥75% of the circumference were eligible for treatment under hospital exemption. Cell sheets were cultured from buccal mucosa according to Good Manufacturing Practice and were endoscopically applied to the post-ESD defect directly after resection. Patients were followed with weekly endoscopy examinations, including confocal laser microscopy, for a total of four weeks., Results: Five patients were treated. ESD was extensive with resections being circumferential in three patients and 9-10 cm in length in two. The number of transplanted cell sheets ranged from two to six. Three patients developed strictures requiring two to five dilatation sessions., Conclusions: Cell sheet transplantation shows to be safe and feasible in a Western population. Results suggest that transplantation has a protective effect on the mucosal defect after ESD, decreasing both the risk for and extent of stricture formation.

Aim: To examine whether rendezvous endoscopic retrograde cholangiopancreatography (ERCP) is associated with less pancreatic damage, measured as leakage of proenzymes, than conventional ERCP., Methods: Patients (n = 122) with symptomatic gallstone disease, intact papilla and no ongoing inflammation, were prospectively enrolled in this case-control designed study. Eighty-one patients were subjected to laparoscopic cholecystectomy and if intraoperative cholangiography suggested common bile duct stones (CBDS), rendezvous ERCP was performed intraoperatively (n = 40). Patients with a negative cholangiogram constituted the control group (n = 41). Another 41 patients with CBDS, not subjected to surgery, underwent conventional ERCP. Pancreatic proenzymes, procarboxypeptidase B and trypsinogen-2 levels in plasma, were analysed at 0, 4, 8 and 24 h. The proenzymes were determined in-house with a double-antibody enzyme linked immunosorbent assay. Pancreatic amylase was measured by an enzymatic colourimetric modular analyser with the manufacturer's reagents. All samples were blinded at analysis., Results: Post ERCP pancreatitis (PEP) occurred in 3/41 (7%) of the patients cannulated with conventional ERCP and none in the rendezvous group. Increased serum levels indicating pancreatic leakage were significantly higher in the conventional ERCP group compared with the rendezvous ERCP group regarding pancreatic amylase levels in the 4- and 8-h samples (P = 0.0015; P = 0.03), procarboxypeptidase B in the 4- and 8-h samples (P < 0.0001; P < 0.0001) and trypsinogen-2 in the 24-hour samples (P = 0.03). No differences in these markers were observed in patients treated with rendezvous cannulation technique compared with patients that underwent cholecystectomy alone (control group). Post procedural concentrations of pancreatic amylase and procarboxypeptidase B were significantly correlated with pancreatic duct cannulation and opacification., Conclusion: Rendezvous ERCP reduces pancreatic enzyme leakage compared with conventional ERCP cannulation technique. Thus, laparo-endoscopic technique can be recommended with the ambition to minimise the risk for post ERCP pancreatitis.

Background: Rendezvous intraoperative endoscopic retrograde cholangiography (RV-IOERC), also called guidewire-facilitated IOERC, is one of the single-stage options available for managing common bile duct stones (CBDS) during laparoscopic cholecystectomy. The objective of this study is to investigate procedure-related complications in IOERC patients and stone clearance., Methods: All patients who underwent IOERC between January 2000 and December 2009 were identified from the local registry of Karolinska University Hospital in Huddinge. Medical charts and ERC reports were studied, and descriptive statistics were obtained. Outcomes were procedure-related complications, especially post-ERCP pancreatitis (PEP), stone clearance, and mortality., Results: 307 patients were identified. In 264 of the patients, the rendezvous cannulation technique was successful (86 %); in the remaining 43 patients, conventional cannulation technique was necessary. In total, PEP occurred in seven patients (2.28 %). One of the PEP patients was in the rendezvous cannulated group (0.37 %), whereas six patients developed PEP in the nonrendezvous group (13.95 %, p < 0.001). The primary stone clearance rate was 88.27 % (271/307). There was no mortality within 90 days in the series., Conclusions: IOERC with RV cannulation technique for management of CBDS during laparoscopic cholecystectomy has a low PEP rate and a high stone clearance rate, making it a safe and feasible method for removing CBDS. However, the technique requires logistics to perform IOERC in the operating theater. The present data suggest that IOERC with RV cannulation is superior to conventional cannulation with respect to risk of PEP.

Pancreatic cancer patients frequently show hyperglycemia, but it is uncertain whether hyperglycemia stimulates pancreatic cancer cells. We have investigated whether excess glucose induces hypoxia-inducible factor-1α (HIF-1α) and stimulates glucose metabolism and cell migration in pancreatic cancer cells. We studied wild-type (wt) MiaPaCa2 pancreatic cancer cells and a MiaPaCa2 subline (namely si-MiaPaCa2) that had HIF-1α-specific small interfering RNA. Wt-MiaPaCa2 cells are known to be HIF-1α-positive in hypoxia and HIF-1α-negative in normoxia, whereas si-MiaPaCa2 cells are devoid of HIF-1α in both normoxia and hypoxia. We incubated these cells with different amounts of glucose and determined HIF-1α mRNA and protein by real-time polymerase chain reaction and western blotting. We determined glucose consumption, lactate production and intracellular hexokinase-II and ATP to assess glucose metabolisms and determined pyruvate dehydrogenase kinase-1, reactive oxygen species and fumarate to assess mitochondrial activities. Further, we studied cell migration using a Boyden chamber. Excess glucose (16.7-22.2mM) increased HIF-1α in hypoxic wt-MiaPaCa2 cells. HIF-1α expression increased ATP contents and inhibited mitochondrial activities. Extracellular glucose and hypoxia stimulated glucose metabolisms independent of HIF-1α. Excess glucose stimulated the migration of wt- and si-MiaPaCa2 cells in both normoxia and hypoxia. Thus, glucose stimulated cell migration independent of HIF-1α. Nevertheless, hypoxic wt-MiaPaCa2 cells showed greater migrating ability than their si-MiaPaCa2 counterparts. We conclude that (1) excess glucose increases HIF-1α and ATP in hypoxic wt-MiaPaCa2 cells, (2) extracellular glucose and hypoxia regulate glucose metabolisms independent of HIF-1α and (3) glucose stimulates cell migration by mechanisms that are both dependent on HIF-1α and independent of it.

The use of artificial nutrition remains controversial for cancer patients in palliative care, and its prevalence is largely unknown. We therefore conducted a national study to investigate the prevalence, indications for, and perceived benefit of enteral/parenteral nutrition and intravenous glucose in this patient group. A cross-sectional study was performed within the palliative care research network in Sweden (PANIS), using a web-based survey with 24 questions on demographics, prescribed nutritional treatment, estimated survival and benefit from treatment. Data was received from 32 palliative care units throughout the country, representing 1083 patients with gastrointestinal and gynecological malignancies being the most common diagnoses. Thirteen percent of the patients received enteral/parenteral nutrition or intravenous glucose. Parenteral nutrition (PN) was significantly more common in home care units serving the urban Stockholm region (11%) than in other parts of the country (4%). Weight and appetite loss were the predominant indications for PN, with this treatment deemed beneficial for 75% of the palliative patients. Data show that there was great variation in PN use within the country. PN was predominately initiated when patients had weight and appetite loss but still had oral intake, indicating a use of PN that extends beyond the traditional use for patients with obstruction/semi obstruction.

Background and Study Aims: The aim of this study was to investigate whether telemedicine can help to ensure high-quality endoscopic retrograde cholangiopancreatography (ERCP) in patients living in rural areas. The study was conducted by investigators from two centers: the Karolinska University Hospital, a high-volume center which provided the teleguided support, and the Visby District Hospital, a low-volume center., Patients and Methods: From September 2010 to August 2011, 26 ERCP procedures performed at a district hospital were teleguided by an experienced endoscopist at the Karolinska University Hospital. To ensure patient data protection, all communication went through a network (Sjunet) that was separate from the Internet and open only to accredited users. The indications for ERCP were common bile duct stones (n = 12), malignant strictures (n = 12), and benign biliary strictures (n = 2). In 15 cases, this was the patient's first ERCP procedure., Results: The common bile duct was successfully cannulated in all 26 teleguided procedures. The local endoscopist scored the teleguided support as crucial for the successful outcome in 8 /26 cases, as an important factor in 8, and as being of less importance in the remaining 10. In the eight cases where the teleguided support was judged to be crucial, six subsequent percutaneous transhepatic cholangiography procedures and two repeat ERCPs were avoided. The overall cannulation rate at the district hospital improved from 85 % to 99 % after teleguided support was introduced. No procedure-related complications occurred., Conclusion: Distant guidance of advanced ERCP procedures in a low-volume center, through teleguided support from a high-volume center, has the potential to improve the quality of care, as reflected in high cannulation rates and the ability to complete the scheduled interventions., (© Georg Thieme Verlag KG Stuttgart · New York.)

Context: The outcome of treatment for patients with chronic pancreatitis may be improved by multidisciplinary management., Objective: To study patients with chronic pancreatitis, especially regarding alcohol use, within a multi disciplinary program., Main Outcome Measures: 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., Results: 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&lt;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)., Conclusions: 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.

Objective: The current study used islet amyloid polypeptide (IAPP) knockout mice (KO mice) to investigate the physiological role of IAPP in the regulation of food intake (FI)., Material and Methods: FI and body weight were measured in KO and wild-type (WT) mice for 27 weeks. In an additional short-term experiment, IAPP (25 pmol·kg(-1)min(-1)) was infused subcutaneously for 3 days in KO and WT mice, and FI, meal pattern, and body weight were analyzed., Results: In the long-term experiment, no significant differences in body weight were seen between WT and KO mice at any point. FI, meal number, and meal size did not differ significantly between the groups in any of the five selected weeks that were studied. In the short-term experiment, FI decreased significantly during IAPP infusion in both WT and KO groups. FI was significantly lower in the KO mice compared with WT on days 1 and 2 (p < 0.05 and p < 0.01, respectively)., Conclusions: The data showing no differences in FI and body weight were seen between KO and WT mice, indicating that FI can be controlled in the absence of IAPP. The more marked anorectic effect seen in the KO mice during IAPP infusion suggests that IAPP receptors and/or IAPP post-receptor signaling pathways are up-regulated in mice lacking endogenous IAPP.

Background: Ischemia-reperfusion injury is a major concern with portal triad clamping (PTC) in liver surgery. Microdialysis allows continuous intraoperative monitoring of tissue metabolism in the liver. Our aim was to evaluate the feasibility of microdialysis as a tool to assess the intrahepatic metabolic effects of PTC in patients undergoing liver resection., Methods: Eleven patients who underwent liver resection were subjected to intrahepatic microdialysis. Dialysis fluid samples were collected before, during, and after a 20-min period of PTC. Glucose, lactate, pyruvate (markers of ischemia), and glycerol (marker of cell membrane damage) were analyzed and the lactate/pyruvate ratio was calculated., Results: During PTC, intrahepatic glucose, lactate, and glycerol increased from 9.1±2.2 to 14.5±2.4 mM, from 2.2±0.3 to 5.8±0.5 mM, and from 63±14 to 142±28 μM, respectively. Pyruvate was unchanged, resulting in an increased lactate/pyruvate ratio (from 39±10 to 104±32). During initial reperfusion, glucose further increased to 16.4±2.9 mM. Pyruvate increased after reperfusion (from 93±18 to 138±23 μM), while lactate was stable, resulting in a normalized lactate/pyruvate ratio. Glycerol continued to increase during initial reperfusion., Conclusions: PTC was associated with considerable intrahepatic metabolic alterations with anaerobic metabolism, increased glycogenolysis, and cellular membrane damage resulting in increased levels of glucose, lactate, glycerol, and lactate/pyruvate ratio. Microdialysis is easy to use and allows continuous monitoring of intrahepatic metabolism during liver surgery., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: 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., Research Design and Methods: 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., Results: 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., Conclusions: 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.

Objective: The association between chronic pancreatitis (CP) and primary sclerosing cholangitis (PSC) has been reported previously. The aims of the present study were to evaluate the presence of early pancreatic abnormalities and duct changes, using MRCP/MRI in PSC and to evaluate possible risk factors for these changes and their clinical importance., Materials and Methods: One hundred and three patients with PSC were identified among all MRI liver/pancreas referrals in 2001-2005. MRCP was used to grade pancreatic duct changes in three groups: grade 0 (normal), grade 1 (mild) and grade 2 (severe). For detection of early MRI signs of CP, the pancreas-spleen signal intensity ratio (SIR), the arterial and early venous phase ratio (A/PV ratio) and the age-related size of the pancreas were evaluated., Results: Pancreatic duct changes were found in 24% of the PSC patients. The pancreatic duct changes were associated with extrahepatic biliary involvement and long duration of PSC but not associated with pancreas-spleen SIR, A/PV ratio, pancreas size, previous post-ERCP or acute pancreatitis. Severe pancreatic duct changes were significantly associated to abdominal pain. Clinically significant CP was seen in one PSC patient (1%)., Conclusions: Pancreatic duct changes are associated with extrahepatic bile duct strictures and not with the early MRI signs of CP. Therefore, pancreatic duct changes seem to be part of the spectrum of PSC and should not be defined as CP. Pancreatic duct changes are of limited clinical importance but may contribute to abdominal pain in PSC.

In this study, we investigated whether the anti-inflammatory drug PP56 (alpha-trinositol) may improve cancer-induced metabolic disorders. We implanted human MiaPaCa2 pancreatic cancer cells in the pancreas of 14 athymic mice for 12 weeks, using six intact littermates as normal controls. During the 12 weeks, seven tumor-cell recipients were treated with PP56 by daily injection (PPT mice). The tumor-cell recipients that were otherwise untreated were used as tumor controls (TC mice). Impaired glucose tolerance and decreased body weight gain were seen in TC but not PPT mice. When an enzyme for fatty acid beta-oxidation namely medium-chain acyl-CoA dehydrogenase (MCAD) was determined in tumor grafts; tumors from PPT mice showed more MCAD than those from TC mice. This suggests that PP56 stimulated fatty acid beta-oxidation in MiaPaCa2 cells in vivo. In keeping with this notion, PPT mice had decreased plasma free fatty acids. In vitro, we demonstrated that MiaPaCa2 cells consumed more fatty acids in the presence of PP56. In another experiment, we infused PP56 or vehicle in normal mice and found that PP56 decreased circulating glucose in the animals. We also showed that PP56 increased glucose transport in L6 skeletal muscle cells in vitro. In conclusion, PP56 increases the turnover of circulating nutrients such as glucose and helps maintain energy homeostasis in mice with pancreatic cancer.

Background: The regulatory gene pathways that accompany loss of adipose tissue in cancer cachexia are unknown and were explored using pangenomic transcriptome profiling., Methods: Global gene expression profiles of abdominal subcutaneous adipose tissue were studied in gastrointestinal cancer patients with (n=13) or without (n=14) cachexia., Results: Cachexia was accompanied by preferential loss of adipose tissue and decreased fat cell volume, but not number. Adipose tissue pathways regulating energy turnover were upregulated, whereas genes in pathways related to cell and tissue structure (cellular adhesion, extracellular matrix and actin cytoskeleton) were downregulated in cachectic patients. Transcriptional response elements for hepatic nuclear factor-4 (HNF4) were overrepresented in the promoters of extracellular matrix and adhesion molecule genes, and adipose HNF4 mRNA was downregulated in cachexia., Conclusions: Cancer cachexia is characterised by preferential loss of adipose tissue; muscle mass is less affected. Loss of adipose tissue is secondary to a decrease in adipocyte lipid content and associates with changes in the expression of genes that regulate energy turnover, cytoskeleton and extracellular matrix, which suggest high tissue remodelling. Changes in gene expression in cachexia are reciprocal to those observed in obesity, suggesting that regulation of fat mass at least partly corresponds to two sides of the same coin.

Objective: To evaluate whether upregulation of liver and muscle uncoupling protein 2 (UCP-2) is an acute phenomenon in obstructive jaundice and associated with secondary metabolic effects., Methods: Male Sprague-Dawley rats were divided into four groups: bile duct ligated (BDL) and sham-operated pair-fed (PF), ad libitum fed (AL), and controls. BDL, PF, and AL rats were further divided into subgroups according to the interval postoperatively when they were reanesthetized and sampled for tissue and blood: 2, 4, and 8 d, respectively. Bilirubin, liver enzymes, glucose, free fatty acids, and insulin in blood plasma were analyzed. Liver and muscle tissue were sampled for UCP-2 and adenosine triphosphate analysis., Results: The BDL rats showed an increase of the liver UCP-2 expression compared with PF and AL rats (P<0.05) 4 d postoperatively. Liver adenosine triphosphate in BDL rats showed a decrease compared with sham-operated controls at all intervals (P<0.05). Plasma glucose concentration in BDL rats was decreased compared with the other groups. Free fatty acids showed an initial increase 2 d postoperatively compared with sham-operated controls and PF and AL rats (P<0.05) at the corresponding time point., Conclusion: Obstructive jaundice is associated with an early upregulation of liver UCP-2, reduced liver adenosine triphosphate content, and decreased plasma glucose concentration, supporting the hypothesis that obstructive jaundice results in impaired energy homeostasis in the liver, which might cause decreased glucose output and hypoglycemia as a consequence., (Copyright 2010 Elsevier Inc. All rights reserved.)

We investigated whether cells expressing hypoxia-inducible factor-1α (HIF-1α) are specially related to blood vessels in human pancreatic tumors. HIF-1α and blood vessels were stained in 7 pancreatic ductal adenocarcinomas (PDAC) and 3 nonmalignant tumors. HIF-1α(+) cells accounted for 37 ± 5% of the total PDAC cells and increased to 52 ± 4% in perivascular PDAC cells and to 67 ± 4% in PDAC cells found in intratumoral blood vessels. In nonmalignant tumors, 12 ± 3% of the total tumoral cells examined were HIF-1α(+), and HIF-1α(+) cells decreased to 2 ± 0.3% in perivascular cells examined in the tumors. In conclusion, HIF-1α(+) cells in PDAC and nonmalignant pancreatic tumors differ not only in their amounts but also in their relation to intratumoral blood vessels. HIF-1α(+) cells usually are adjacent to intratumoral blood vessels in PDAC tumors, but are farther away from the vessels in nonmalignant pancreatic tumors., (Copyright © 2010 S. Karger AG, Basel.)

In this study, patients' views and experiences of using home artificial nutrition, and factors associated with use of home parenteral nutrition (HPN) were investigated. Structured telephone interviews with 620 cancer patients enrolled in 21 palliative home care services were analysed. HPN was more common (11%) than home enteral tube feeding (HETF, 3%). Home artificial nutrition (including HPN and HETF) was usually introduced more than four months before death. Three of four HPN recipients also had oral food intake. HPN use was associated with eating difficulties, nausea/vomiting, and fatigue rather than gastrointestinal problems per se. HETF was generally used for patients with problems related to oesophagus and head and neck tumours. In conclusion the results suggest that, contrary to existing guidelines, HPN is used to supplement oral intake, and not only for patients with a non-functioning gastrointestinal tract.

The purpose of this study was to evaluate the accuracy of diffusion-weighted imaging (DWI) in diagnosis of pancreas cancer, to compare DWI with a conventional comprehensive MRI (MRI-c) and to analyse apparent diffusion coefficient (ADC) values of lesions. Thirty-six patients with pancreatic lesions (12 malignant and 24 benign) and 39 patients without lesions were included. MRI-c and DWI (free breathing, b values 0 and 500 s/mm(2)) were performed prospectively and consecutively in a 1.5-T system. The analysis was retrospectively performed blinded by two radiologists in consensus. The sensitivity, specificity, accuracy, and positive and negative predictive values of DWI and MRI-c were 92, 97, 96, 85, 98% and 100, 97, 97, 86, 100%, respectively. Mean ADC values of malignant lesions were significantly lower than those of benign lesions. DWI has a similar accuracy to MRI-c in diagnosis of pancreas cancer.

In this study, we investigated whether increased dietary fat influences established pancreatic cancer cells. MiaPaCa2 human pancreatic cancer cells were grown orthotopically in athymic mice fed normal diet (ND) or high-fat diet (HF). In the resulting tumors, medium-chain acyl-coenzyme A dehydrogenase (MCAD, a regulator of fatty acid beta-oxidation) and Cu/Zn-superoxide dismutase (an antioxidant enzyme) were determined using Western blotting. The MCAD messenger RNA (mRNA) was determined by real-time polymerase chain reaction. Intracellular lipid droplets, proliferating cells (Ki67 positive), and apoptotic cells were stained in tumor sections. The HF tumors were heavier than the ND tumors (1.60 +/- 0.08 vs 1.13 +/- 0.10 g, P < .01, 6 tumors per group). The MCAD and Cu/Zn-superoxide dismutase proteins and the MCAD mRNA were increased in HF tumors compared with those seen in ND tumors. The HF tumors contained extensive central necrosis, which was surrounded with apoptotic and proliferating cells. The HF tumors also showed numerous lipid droplets. In the ND tumors, necrosis was uncommon, apoptotic cells were sporadic, and lipid droplets were few. In follow-up experiments, MiaPaCa2 cells were incubated in vitro in the presence or absence of fatty acids (oleic and linoleic acids). The fatty acid exposure increased lipid droplets, cell proliferation, and MCAD mRNA expression in MiaPaCa2 cells. In conclusion, increased dietary fat stimulates lipid metabolism and cell turnover in MiaPaCa2 human pancreatic cancer cells.

Background: Massive hemorrhage results in hypovolemia and hypotension that activate the sympathetic-adrenal-system, the hypothalamic-pituitary-adrenal axis, and induce metabolic changes such as hyperglycemia. Blood loss during surgery, however, is rapidly compensated by intravenous fluids to minimize negative impact on circulation. The aim of this study was to develop an experimental model for studies of the stress response and metabolic alterations seen after major abdominal surgery by combining intestinal resection with compensated non-hypotensive blood loss., Material and Methods: Intestinal resection in the rat was combined blood loss (7% and 16% of total blood volume) with subsequent fluid replacement (2 x volume of saline + hydroxyethyl starch, 50:50) to investigate the effects on blood pressure, plasma adrenaline, noradrenaline (0-2 h postoperatively), glucose, insulin, corticosterone, and hematocrit (0-24 h postoperatively)., Results: Surgical trauma alone or in combination with blood loss and fluid replacement did not decrease mean arterial blood pressure (MAP) compared with anesthetized controls. Plasma levels of catecholamines were unchanged during the period of blood loss. After surgery and blood loss, plasma glucose showed a blood loss volume-dependent increase up to 12 h postoperatively compared to surgery alone (P < 0.001-0.05). Plasma corticosterone increased after surgery alone and in combination with blood loss but the changes were not dependent on the magnitude of blood loss., Conclusions: Surgical trauma combined with compensated non-hypotensive blood loss induced persistent volume-dependent hyperglycemia that did not depend on changes in plasma corticosterone and, in the early postoperative phase, MAP and catecholamines. Our data indicate that blood loss per se, without causing hypotension or acute elevations in catecholamines, can induce marked postoperative hyperglycemia. The experimental model presented in this report will be a useful tool to further elucidate mechanisms underlying the changes in glucose metabolism seen after surgical injury.