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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.

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.

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.Patients with Barrett's oesophagus associated high-grade dysplasia or early adenocarcinoma where ESD entailed a resection3 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.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.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.

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.

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 r) is used for continuous infusion in advanced Parkinsons 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. Funding Agencies|AbbVie AB

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.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.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.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.

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.

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.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.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%).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, 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.

Cancer cachexia is an important, negative prognostic marker that has been linked to systemic inflammation and cell death through unclear mechanisms. A key feature of cancer cachexia is loss of white adipose tissue (WAT) because of increased adipocyte lipolysis and possibly reduced lipid synthesis (lipogenesis). In this study, the authors investigated whether alterations in fat cell numbers, lipogenesis, or cytokine and/or leukocyte infiltration could account for some of the functional changes observed in WAT in cancer cachexia.Blood and subcutaneous WAT samples were obtained from a 10 weight-stable patients, from 13 weight losing (cachexia) patients with cancer, and from 5 patients without cancer (noncancer patients) who initially were classified with cancer.Systemic inflammation (increased circulating levels of interleukin 6 [IL-6]) and enhanced lipolysis were confirmed in the cachectic patients compared with the other patients. However, the messenger RNA expression of IL-6 and other cytokine or leukocyte markers, as well as WAT secretion of IL-6, were not altered in the patients with cachexia. Thus, the elevated serum levels of IL-6 that were observed in cachexia were not derived from WAT. Insulin-induced lipogenesis in adipocytes from patients with cachexia was the same as that in adipocytes from patients with weight-stable cancer and from noncancer patients (2.5-fold maximal stimulation; half-maximum effective concentration, approximately 0.03 nmol/L). Fat cell size was decreased but adipocyte numbers were normal in cancer patients with cachexia, suggesting that there was no major fat cell death.The current findings indicated that subcutaneous WAT does not contribute to the systemic inflammatory reaction and does not induce adipocyte insulin resistance in cancer cachexia. Moreover, increased fat cell lipolysis, not reduced lipogenesis or adipocyte cell death, appeared to be the primary cause of fat loss in this condition.

We have studied the use of video-mediated technology to facilitate multidisciplinary meetings where consensus is reached about the diagnosis and treatment of patients. The meetings involved 2–5 sites, with 1–20 participants from each site, and concerned patients with severe diseases in the upper abdomen. During a period of about one year we conducted observations and interviews at the Karolinska hospital and some of the local hospitals. Eight video-mediated consensus meetings were video-recorded and transcribed. The audio and the radiology images presented during the meetings were considered to be most important; video was not critical for the consensus meeting itself, but contributed to a feeling of awareness and social presence. We conclude that video-mediated consensus meetings are affected by the technology used, and certain changes in the technology or environment could improve the meetings. Without the technology, such meetings would lead to more travelling for the patient and for the medical staff involved.

The aim of this study was to investigate the nutritional risk status and use of nutritional support among cancer patients enrolled in palliative home care services. Differences in the use of nutritional support in relation to nutritional, social and clinical factors, as well as survival were also investigated.Structured telephone interviews were conducted with cancer patients enrolled in all 21 palliative home care services in the Stockholm region. An interview guide was designed to investigate topics related to the patient's nutritional situation.Interviews with 621 patients were analysed. Sixty-eight percent of the patients were scored as at nutritional risk according on a modified version of NRS-2002. Nutritional support was used by 55% of the patients, with oral nutritional supplements most common and 14% using artificial nutrition. Use of nutritional support was related to low BMI and severe weight loss and was more common in patients with shorter survival times.These findings demonstrate that nutritional support is used to treat already malnourished patients with shorter survival time, rather than to prevent malnutrition. A more structured approach to nutritional issues for patients in palliative phases, which considers life expectancy and psycho-social aspects of nutritional issues, could help identify potential candidates for nutritional support.

A 7-year-old girl with severe hereditary pancreatitis underwent total pancreatectomy. A total of 160,000 islet equivalents (6400 islet/kg) were transplanted to the brachioradialis muscle of the right forearm. Her plasma C-peptide level was undetectable after pancreatectomy but increased to 1.37 ng/mL after 17 days; at this time point, her insulin requirement was 0.75 units of insulin/kg/day. At 5- and 27-months, her hemoglobin A1c (HbA1c) and insulin requirements were 4.5 and 5.3% and 0.3 and 0.18 units/kg/day, respectively. Basal and stimulated C-peptide levels were 0.67 +/- 0.07 and 3.36 +/- 1.37 ng/mL, respectively. Stimulated insulin levels were 30% higher in the islet-bearing arm compared to the contralateral arm after glucagon stimulation. After surgery and islet transplantation, the quality of life improved dramatically and she gained 8 kg of weight. In summary, a normal HbA1c, a low insulin requirement and the absence of recurrent hypoglycemia and the gradient of insulin between the arms indicate that the intramuscularly transplanted islets contribute to a long-term clinically significant metabolic control.

After pancreaticoduodenectomy (PD) patients may be deficient in essential micronutrients. This study was designed to determine if this is a consequence of surgery.Long-term survivors (6 months) of PD for peri-ampullary neoplasia and healthy controls (patients' spouse/partner) were enrolled in the study. Specific clinical parameters were recorded, serum micronutrient levels were measured and subjects completed 7-day food diaries.Thirty-seven patients were studied, 25 with paired controls. All were well nourished, as defined by body mass index and food diary analysis. Patients with paired controls were representative of all patients studied. Patients had raised transferrin (median 2.60 vs. 2.16 g/l, p = 0.001) and low ferritin levels (34.9 vs. 119.0 g/l, p0.001) indicating relative iron deficiency. Patients also demonstrated lower levels of the anti-oxidants selenium (0.77 vs. 0.93 micromol/l, p0.001) and vitamin E (23.2 vs. 35.7 micromol/l, p0.001) with 57% of patients having frank selenium deficiencies. Patients had lower levels of vitamin D than controls (15.7 vs. 19.6 micromol/l, p = 0.001) and 30% of patients had a raised parathyroid hormone level, suggesting compensatory mechanisms operate to maintain normocalcaemia.Long-term survivors of PD are relatively deficient in several micronutrients compared to non-operated controls taking the same diet. We recommend that micronutrient status should be regularly checked in these patients and treated where necessary.

With a worldwide incidence of more than 200 000 cases and almost as many deaths, pancreatic carcinoma (PC) remains one of the leading causes of cancer deaths, especially in the Western world. Due to the late onset of symptoms, almost all patients suffer from disseminated disease at the time of diagnosis and only a minority will ever be candidates for radical surgery. Only about one tenth of the operated patients remain disease free. For these reasons, development of effective palliative systemic therapy is important. Almost a decade ago, gemcitabine replaced 5-Fu as the gold standard in systemic treatment of advanced PC. Since then, a number of trials have investigated the potential additional effect of several cytotoxic or targeted agents in combination with gemcitabine. As shown in this review, nearly all these trials have proved disappointing. This review provides an overview of the results of current phase III trials of gemcitabine based systemic therapy. Furthermore, we discuss the role of systemic therapy compared to BSC only and the potential future role of targeted therapies. Survival in patients with infiltrating ductal adenocarcinoma of the pancreas (PC) is limited [1]. The majority of patients have metastases or locally advanced disease at diagnosis rendering them unsuitable for potentially curative resections [2]. This fact, as well as the relative ineffectiveness of existing treatments for localized disease, implies that most patients will be considered for systemic therapy. For many years, 5-Fu was considered the most active chemotherapeutic agent for systemic treatment in patients with advanced PC. Currently, gemcitabine has taken the role as the drug of choice and it is, despite its limited activity, considered gold standard for the control arm in the evaluation of new therapies. This far, combination chemotherapy has not proven more efficacious than single drug therapy. This fact has increased the interest for alternative therapeutic strategies, e.g. targeted therapies. The relative inefficacy of systemic therapy has also raised the question whether patients with advanced PC still should be recommended best supportive care (BSC) only. An overview of systemic chemotherapy in pancreatic cancer of all stages was performed by the Swedish Council of Technology Assessment in Health Care (SBU) in 2001 [3]. Herein, we present an update of the current status on and the indication for systemic therapy for advanced PC.

Although Helicobacter pylori (H. pylori) seropositivity is linked to an excess risk of pancreatic cancer, the biologic mechanism is unknown. Gastric ulcer is primarily associated with corpus colonization of H. pylori, atrophic gastritis and formation of N-nitrosamines. Duodenal ulcer is a marker of antral colonization, hyperacidity and uninhibited secretin release. We estimated relative risks for pancreatic cancer among patients with gastric or duodenal ulcer, based on a register-based retrospective cohort study with 88,338 patients hospitalized for gastric ulcer and 70,516 patients for duodenal ulcer recorded in the Swedish Inpatient Register between 1965 and 2003. Following operation, the 14,887 patients who underwent gastric resection and 8,205 with vagotomy were analyzed separately. Multiple record-linkages allowed complete follow-up and identification of all incident cases of pancreatic cancer until December 31, 2003. Standardized incidence ratios (SIRs) estimated relative risks. During years 3-38 of follow-up, we observed a 20% excess risk (95% confidence interval [CI] 10-40%) for pancreatic cancer among unoperated gastric ulcer patients. The excess increased to 50% (95% CI 10-110%) 15 years after first hospitalization (p for trend = 0.03). SIR was 2.1 (95% CI 1.4-3.1) 20 years after gastric resection. Unoperated duodenal ulcer was not associated with pancreatic cancer risk, nor was vagotomy. Our results lend indirect support to the nitrosamine hypothesis, but not to the hyperacidity hypothesis in the etiology of pancreatic cancer.

High meat consumption has been associated with increased risk of pancreatic cancer in several, although not all, case-control studies. However, prospective data on this relationship are sparse, and the results have been inconsistent. We prospectively evaluated meat, fish, poultry, and egg consumption in relation to pancreatic cancer incidence in a population-based cohort of 61,433 Swedish women. Diet was assessed with a food-frequency questionnaire at baseline (1987-1990) and again in 1997. Pancreatic cancers were ascertained through linkage to the Swedish Cancer Register. Cox proportional hazards models were used to estimate multivariate hazard ratios with 95% confidence intervals (CI). During the 941,218 person-years of follow-up, from 1987 through 2004, 172 incident cases of pancreatic cancer were diagnosed. Long-term red meat consumption (using data from both dietary questionnaires) was positively associated with risk of pancreatic cancer (p-trend = 0.01), whereas long-term poultry consumption was inversely (p-trend = 0.04) associated with risk. The multivariate hazard ratios for the highest versus the lowest category of consumption were 1.73 (95% CI = 0.99-2.98) for red meat and 0.44 (95% CI = 0.20-0.97) for poultry. There were no significant associations with processed meat, fish or egg consumption. Findings from this prospective study suggest that substituting poultry for red meat might reduce the risk of pancreatic cancer.

We examined the associations of body mass index (BMI), waist circumference, a history of diabetes, and cigarette smoking with risk of pancreatic cancer among 37,147 women and 45,906 men followed up during 560,666 person-years in the Swedish Mammography Cohort and the Cohort of Swedish Men; 136 incident cases of pancreatic cancer were diagnosed. The multivariate rate ratio (RR) of pancreatic cancer for obese women and men (BMI > or =30 kg/m(2)) was 1.81 (95% CI: 1.04-3.15) compared to those with a BMI of 20-25 kg/m(2). For a difference of 20 cm (about two standard deviations) in waist circumference, the multivariate RRs were 1.32 (95% CI: 0.73-2.37) among women and 1.74 (95% CI: 1.00-3.01) among men. Pancreatic cancer risk was associated with history of diabetes (multivariate RR: 1.88; 95% CI: 1.09-3.26) and cigarette smoking (multivariate RR for current compared with never smokers: 3.06; 95% CI: 1.99-4.72). Current smokers of > or =40 pack-years had a five-fold elevated risk compared with never smokers. Risk among past smokers approached the RR for never smokers within 5-10 years following smoking cessation. Findings from this prospective study support positive relationships of overall obesity, abdominal adiposity, diabetes and smoking with risk of pancreatic cancer.

A dysregulated immune response has been suggested to be important for the pathogenesis of chronic pancreatitis (CP). Formation of immunological memory is based on the differentiation of naive T lymphocytes to memory T lymphocytes after exposure to antigens and specific cytokines. The aim of this study was to analyze peripheral blood mononuclear cells (PBMCs) in patients with CP for different T lymphocyte subsets including naive and memory T cells.PBMCs from 9 patients who had undergone pancreatic resection due to CP, 9 CP patients who had not been resected and 9 healthy controls were analyzed by flow cytometry.Patients with CP had a skewed distribution of T lymphocytes, with an increased level of CCR7+/CD45RA- central memory T lymphocytes compared to healthy controls. Nonresected CP patients and subjects who had undergone pancreatic resection due to CP had similar levels of central memory T lymphocytes.Our results indicate that the dysregulation of the immune system in chronic pancreatitis seems to persist even after removal of large parts of the local inflammatory site. We suggest that the increase of central memory T lymphocytes may be important for maintaining the inflammatory process in chronic pancreatitis.

This experiment investigated the influence of age on prefrontal acetylcholine (ACh) release and Fos response in the hypothalamic paraventricular nucleus and the nucleus tractus solitarius (NTS) of rats following isoflurane anesthesia. It is known that isoflurane decreases acetylcholine release in most brain regions. In the present study, we found that the level of prefrontal acetylcholine was significantly lower in 28-month-old rats (14% of baseline) than in 3-month-old rats (38% of baseline) during 2 h of isoflurane anesthesia (P < 0.05). The old rat group showed significantly greater Fos induction in the paraventricular nucleus compared to the young adult rat group (P < 0.05), indicating that the old rats were subjected to stress. No difference in Fos response was noted in the nucleus tractus solitarius. The old rats displayed a significant increase in feeding behavior during the 3-h recovery period (P < 0.05), but there was no difference in overall acetylcholine levels. Taken together, these findings suggest that isoflurane anesthesia influences old rats more profoundly than young adult rats with regard to reductions in acetylcholine release and stress responses. This may have implications for understanding the development of postoperative delirium in aged patients.

Obesity is associated with increased severity in patients with acute pancreatitis (AP). The underlying mechanisms are unknown. Genetically obese rats exhibit decreased survival rate in experimental AP, but the clinical relevance of this model of obesity may be questioned. It is proposed that development of organ failure in AP occurs in two stages: initial priming of leucocytes followed by a second inflammatory attack. The aim was to evaluate the impact of diet-induced obesity on outcome in a 'two-hit' model of AP.Lipopolysaccharide (LPS) was injected i.p. 3 h after retrograde bile duct infusion of sodium taurocholate in rats. Three experiments were done: 1) an LPS dose-response experiment, 2) chronic high-fat feeding (HF) for 16 weeks, and 3) acute HF for 10 days. Control rats received normal chow. Obesity, morphology and survival rate were assessed.LPS dose-dependently decreased survival rate and increased morphological severity. HF increased weight, intra-abdominal and liver fat. Only acute HF induced hyperlipidaemia. In AP, acute obese rats exhibited less pancreatic inflammation, but total histological severity between groups was not different. In the chronic experiment only obese animals succumbed before 24 h of pancreatitis, but 72-h survival rate was not statistically different in either high-fat experiment.An addition of LPS to AP decreases survival rate and intensifies the peri-pancreatic processes. Despite significant obesity, neither hyperlipidaemia nor increased intra-abdominal or hepatic fat influenced local pancreatic injury or survival negatively. The amount of fat per se seems not to be responsible for the deleterious influence of obesity on acute pancreatitis.

OBJECTIVE: Hyperglycaemia associated with insulin resistance is common after trauma and surgical procedures. Both reduced insulin sensitivity and altered insulin secretion may contribute to the impaired glucose homeostasis. We have demonstrated that skeletal muscle insulin resistance is present 2 h after small intestinal resection in rats. In this study, the aim was to investigate insulin secretion in the same experimental model. DESIGN: Small intestinal resection (5 cm) was performed in adult rats. The control animals underwent anaesthesia only. METHODS: The intravenous glucose tolerance test (IVGTT), the hyperglycaemic clamp and in vitro studies in isolated pancreatic islets were performed after surgery. Concentrations of blood glucose, plasma insulin, corticosterone and interleukin-6 (IL-6) were determined 0-5 h postoperatively. RESULTS: The insulin response in the IVGTT was attenuated 2 h (P

Tumor necrosis factor alpha (TNF-alpha) appears to play a role in the cachexia and diabetes seen in patients with cancers. However, increased TNF-alpha is seen in some, but not all, of the cancer patients.The mRNA transcripts of TNF-alpha and its receptors (TNF-RI and TNF-RII) were quantified in blood cells of pancreatic cancer patients, using competitive quantitative reverse transcriptase-polymerase chain reaction. Plasma TNF-alpha was also quantified in these patients by enzyme-linked immunosorbent assay. Control blood came from healthy subjects.The TNF-alpha mRNA transcripts (per microgram of total RNA) were increased in pancreatic cancer patients (6.8 +/- 2.1 x 10(6), n = 10), compared to control (1.2 +/- 0.2 x 10(6), n = 9, p0.05). After the tumour was removed, the TNF-alpha mRNA transcripts were reduced to a level (2.1 +/- 0.8 x 10(6)) similar to the control. In the cancer patients, no significant changes were found in TNF-RI and TNF-RII gene transcription, compared to the controls.The expression of the TNF-alpha gene is upregulated in patients with pancreatic cancer and normalized after the pancreatic tumor is removed. These results are consistent with the concept that TNF-alpha is involved in metabolic disorders associated with pancreatic cancer.

Studies in patients with acute pancreatitis have shown a correlation between obesity and serious complications or a fatal outcome. However, the mechanisms by which obesity aggravates acute pancreatitis are not known. In the present study we used the sodium taurocholate model of pancreatitis to examine the effect of obesity on severity and outcome in acute experimental pancreatitis (AEP).AEP was induced at two degrees of severity by retrograde infusion of sodium taurocholate (0.2 ml x 3% or 0.4 ml x 3.5%) into the pancreatic duct of rats with obesity induced by high-fat diet, genetically obese (GO) rats or lean control rats. Surviving animals were sacrificed 72 h after induction of pancreatitis.In the low-dose experiment, there were no significant differences in pancreatic histology or survival rate between the groups. In the high-dose experiment, the GO rats had a significantly lower 72-h survival rate than the high-fat obese (HFO) or lean control (LC) groups (GO 25% versus HFO 73%, P0.05; GO 25% versus LC 100%, P0.001). Survival rates in the high-dose experiment correlated strongly with basal liver fat content (R2 = 0.86). Pancreatic histology showed significantly more fat necrosis and a higher total pathological mean score in the HFO rats than in the LC animals (both P0.05).Obesity had a negative influence on the outcome of necrotizing pancreatitis that was related to the magnitude of the pancreatic insult. The sodium taurocholate model in obese rats would be useful for future mechanistic studies of the effect of obesity on pancreatitis.

The diabetes that frequently occurs in pancreatic cancer patients is characterized by profound peripheral insulin resistance. The intracellular mechanism of this insulin resistance was investigated in skeletal muscle biopsies from pancreatic cancer patients with or without diabetes and control subjects. Insulin receptor (IR) binding, tyrosine kinase activity, IR messenger RNA (mRNA), IR substrate-1 content, GLUT-4, and GLUT-4 mRNA content were all normal in pancreatic cancer patients. In contrast, multiple defects in glycogen synthesis were found in pancreatic cancer patients, especially in those with diabetes. Glycogen synthase I activity, total activity, and mRNA levels were significantly decreased in pancreatic cancer patients compared with controls. The fractional velocity of glycogen synthase was decreased only in the diabetic pancreatic cancer group. Glycogen phosphorylase a and b activities were increased in diabetic pancreatic cancer patients, but glycogen phosphorylase mRNA levels were not significantly different. The insulin resistance associated with pancreatic cancer is associated with a post-IR defect, which impairs skeletal muscle glycogen synthesis and glycogen storage.

Objective: Early postoperative enteral feeding has been reported to stimulate intestinal mucosa proliferation. Dietary components influence the intestinal adaptive response after resection and glutamine is a preferential nutrient to enterocytes. The purpose of this study was to evaluate the effects of bolus glutamine supplementation on intestinal adaptation. Methods: Male Wistar rats underwent a 65% small bowel resection. The rats were divided into three groups receiving glutamine 2 g/kg/day, isonitrogenous glycine or saline by gavage for 10 days. All the rats were provided with ordinary rat chow ad libitum. Sampling was done 10 days after resection. Animals fed ordinary rat chow without surgery or specific treatment served as control. Results: Mucosal wet weight, DNA, RNA, protein contents and sucrose activity, as well as villus height increased in the ileal remnant. No significant differences in any of these parameters or body weight could be found between the three groups. Conclusion: Postoperative enteral bolus glutamine supplementation at a dose of 2 g/kg b.w. did not enhance the adaptation of the residual intestine 10 days after massive intestinal resection in the rat.

Background: Intestinal resection stimulates the synthesis and release of gastrointestinal peptides that regulate the growth and adaptation of the mucosa. Luminal nutrients are necessary for optimal proliferation and glutamine is the preferential nutrient to the small bowel. The interplay between glutamine and regulatory peptides could be important in treating short bowel syndrome. Methods: 63 Sprague-Dawley rats were divided into 3 groups: resection; transection, or controls. After intestinal resection animals were orally fed either a diet without glutamine or a glutamine-supplemented diet for 2 days. Transected animals and controls without prior surgery were fed the same two diets. Epidermal growth factor (EGF), transforming growth factor-α, insulin-like growth factors I and II (IGF-I and IGF-II), peptide YY (PYY), and enteroglucagon were analyzed in mucosa from the proximal jejunum, distal ileum as well as in portal plasma when the animals were euthanized 72 h after surgery. Results: Intestinal resection resulted in an early increase in portal plasma concentrations of PYY, EGF, enteroglucagon, and mucosal IGF-II and EGF content that were significant in glutamine-treated animals. Glutamine significantly increased PYY in portal blood after resection (p < 0.05). Conclusion: Glutamine could be of importance for the functional adaptation of residual small bowel mucosa by increasing PYY release.

The development of front-line endoscopic technology has introduced new opportunities during endoscopic retrograde cholangiopancreatography (ERCP) to single-handedly allow direct inspection of detailed structures of the biliary and even the pancreatic duct. This paper presents a new flexible technology delivered with an outer diameter of 0.9 mm giving an image transmission of 6000 pixels. We report on a case where direct inspection of an alleged duct defect, of potential pathogenetic significance, was considered essential in order to substantiate the subsequent clinical management.

The diabetes or impaired glucose tolerance that occurs in most patients with pancreatic cancer is characterized by profound insulin resistance. Recent evidence suggests that the diabetes may result from the presence of the tumor rather than being a predisposing factor to development of the malignancy. Some islet hormones have been shown to exhibit diabetogenic effects. To investigate the potential role of these hormones in the diabetic state associated with pancreatic cancer, we measured islet hormones during fasting in pancreatic cancer patients (n = 30), patients with other malignancies (n = 43), and healthy controls (n = 25). Preoperative pancreatic cancer patients were classified as normal glucose tolerance (NGTT), impaired glucose tolerance (IGTT), non-insulin-requiring diabetes (NIRD), and insulin-requiring diabetes (IRD). Nine pancreatic cancer patients were studied after tumor removal by subtotal pancreatectomy. Some preoperative pancreatic cancer patients (n = 19), postoperative patients (n = 9), and controls (n = 8) were also studied during hyperglycemia and following glucagon injection. Fasting plasma C-peptide was elevated in NIRD pancreatic cancer patients compared to controls. Fasting levels of islet amyloid polypeptide (IAPP), glucagon, and somatostatin were elevated in NIRD and IRD patients. IAPP and glucagon, but not somatostatin, normalized following subtotal pancreatectomy. During hyperglycemia, increases in C-peptide and IAPP were seen only in controls and in NGTT and postoperative pancreatic cancer patients. After glucagon infusion, IAPP levels increased in controls and nondiabetic cancer patients; C-peptide levels increased in controls, nondiabetic patients, and NIRD. Responses of C-peptide and IAPP to glucagon normalized after pancreatectomy. During hyperglycemia, glucagon levels fell in all groups except IGTT patients and a decrease in somatostatin concentrations was seen in controls.

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.

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. 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. 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

Background. For many tumors, therapeutic options are sparse beyond the guidelines, especially for pancreatic cancer. At the same time, more and more biomarkers are known, informing about or supporting treatment decisions. Finally, tumor DNA analysis with next generation sequencing (NGS) is quickly becoming a routine test, at least for tumors. However, to analyse the vast amount of data and provide concrete, evidence-based treatment recommendations has been a challenge. Methods. Applying NGS in a quality controlled set-up together with the newly developed evidence-based software tool EngineusGUIDETM (CE-marked). Results. During the time from Oct 2013 until Oct 2015, 87 patients were analysed with EngineusGUIDE. In 7 cases, more than one tumor was investigated. NGS was performed (WXS = 48; panel/paired = 16, panel = 23). Sequencing could be performed in all but one patient (Whole Exome; bone metastasis). Sequencing quality was insufficient for analysis in 3 cases (paired panel), sequencing revealed insufficient tumor content in the sample for one patient (Whole Exome) leaving 82 patients. The indication was: Pancreatic Neoplasms = 21 cases; Colorectal Neoplasms = 12; Breast Neoplasms = 5; CUP = 6; NSCLC = 3; 2 cases each for Bronchial Neoplasms, Adenoid Cystic Carcinoma, Common Bile Duct Neoplasms, Glioblastoma, Multiple Myeloma, Prostatic Neoplasms and 1 case each for Adenocarcinoma, Duodenal Neoplasms, Endometrial Neoplasms, Hemangiosarcoma, Hypopharyngeal Neoplasms, Leukemia (Lymphocytic, Chronic, B-Cell), Liposarcoma, Liver Neoplasms, Lung Neoplasms, B-Cell Lymphoma, Mantle-Cell Lymphoma, Meningioma, Oropharyngeal Neoplasms, Ovarian Neoplasms, Paranasal Sinus Neoplasms, Parathyroid Neoplasms, Sarcoma, Sigmoid Neoplasms, Squamous Cell Neoplasms, Stomach Neoplasms, Thyroid Neoplasms, Urinary Bladder Neoplasms, Uveal melanoma. In 67/82 patients, druggable targets (response biomarkers) could be identified (range 0-8; median 2). In 45/82 patients (range 0-5; median 1) biomarkers indicated lack of efficacy (e.g. KRAS mutation in CRC). In 65/82 patients, biomarkers indicated increased toxicity (range 0-7; median 2), in 19/82 patients FDA-approved biomarkers for toxicity were detected (28 biomarkers). Of the positive biomarkers, 40 biomarkers in 26 patients indicated drugs approved in the indication, 75 biomarkers in 45 patients indicated approved drugs, and 58 biomarkers in 39 patients indicated experimental drugs (pre-clinical and phase I - III). Six patients have already received drugs recommended by EngineusGUIDE. In 11 patients, toxicity markers may explain observed toxicity during previous treatment. We are currently collecting the outcome parameters of EngineusGUIDE recommendations. Citation Format: Matthias Löhr, Katrin Stecker, Caroline Huelsewig, Sandra Morandell, Isin Ertongur, Sarah Luke-Glaser, Anna Laib, Linnéa Malgerud, Carlos Fernández Moro, Masoud Karimi, Johan Permert, Rainer Heuchel, Johan Lindberg, Valtteri Wirta, Alexander Picker, Marco Del Chiaro, Stephan L. Haas, Caroline S. Verbek, Lars Engstrand, Jens Siveke, David Jackson, Henrik Grönberg, Dirk Jäger, Stephan Brock. An evidence-based software tool for personalized cancer medicine to recommend therapeutic options and avoid toxicity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3165.

Objective: To investigate the potential of a series of growth factors which may be involved in liver regeneration. Design: The concentrations of epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha) and insulin-like growth factor I (IGF-I) were measured in plasma and liver tissue 48h after liver resection or sham operation combined with malnutrition. Methods: Forty-four rats were randomized to either semistarvation or ordinary food intake; half of each group was partially hepatectomized, and the other half underwent a sham operation and served as controls. Growth factors were measured by radioimmunoassay. Results: Plasma EGF levels were increased following semistarvation and were also increased in plasma and liver tissue after 48 h of liver regeneration

Diabetes in patients with pancreatic cancer occurs in 70% to 80% of the patients and is characterized by high plasma levels of insulin. In type II diabetes that is not associated with pancreatic cancer, peripheral insulin resistance and impaired muscle glycogen synthesis are major pathogenic factors. We investigated peripheral insulin sensitivity in patients with pancreatic cancer before and after tumor removal. The effects of pancreatic tumor extracts on glycogen synthesis in skeletal muscle in vitro and the tumor content of pancreatic islet hormones were also investigated. Marked peripheral insulin resistance was found in the patients with pancreatic cancer and was more pronounced in the diabetic patients than in the nondiabetic patients. Insulin sensitivity was not correlated with weight loss, tumor size, or bilirubin levels but improved after surgery. Tumor extracts from diabetic patients with pancreatic cancer caused a marked reduction of glycogen synthesis in skeletal muscle in vitro . All tumors contained islet hormones but not in concentrations sufficient to explain the effect on glycogen synthesis. These findings indicate that a diabetogenic factor associated with pancreatic adenocarcinomas could be involved in the development of the profound peripheral insulin resistance and thereby could contribute to the high incidence of diabetes observed in patients with pancreatic cancer.

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.

The stress response to surgery is characterized by activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, and by an inflammatory response and hyperglycemia. The aim of the present study was to investigate if preoperative corticosterone could reduce the postoperative systemic stress response, without aggravating hyperglycemia or interfering with activation of the hypothalamic-pituitary-adrenal axis, in a standardized rat model of surgical trauma. We used a standardized experimental model of intestinal resection in the rat. Exogenous corticosterone (8 mg/kg body weight) or vehicle was administered 2 hours before surgery; and postoperative plasma concentrations of interleukin-6, interleukin-10, adrenaline, noradrenaline, glucose, and insulin were determined. Exogenous corticosterone decreased preoperative plasma adrenaline but did not change plasma glucose or insulin levels. Moreover, corticosterone reduced postoperative plasma interleukin-6, catecholamines, and glucose (all P < .001-.05) without any effect on the plasma corticosterone concentration compared with vehicle-treated controls. A preoperative 2-hour exposure of physiologic poststress corticosterone concentrations not only suppressed plasma IL-6 levels but also inhibited surgery-induced adrenaline release and suppressed plasma glucose levels. We hypothesize that glucocorticoids attenuated the inflammatory response in injured tissues that reduced afferent input into brain areas regulating the neuroendocrine response.

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.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).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 (P0.001-0.05). Plasma corticosterone increased after surgery alone and in combination with blood loss but the changes were not dependent on the magnitude of blood loss.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.

Clinical islet transplantation is currently being explored as a treatment for persons with type 1 diabetes and hypoglycaemia unawareness. Although 'proof-of-principle' has been established in recent clinical studies, the procedure suffers from low efficacy. At the time of transplantation, the isolated islets are allowed to embolise the liver after injection in the portal vein, a procedure that is unique in the area of transplantation. A novel view on the engraftment of intraportally transplanted islets is presented that could explain the low efficacy of the procedure.

In the subdiaphragmatic vagal deafferentation procedure (SDA), the afferent fibers of the vagus are surgically severed unilaterally where they enter the brain stem. The technique includes a subdiaphragmal truncal vagotomy performed on the contralateral side. This procedure has been used to study the control of food intake, but it has not been used previously to investigate the role of vagal afferent fibers in the control of gastric emptying (GE). The current experiment studied the effect of SDA on the inhibition of GE by islet amyloid polypeptide (IAPP or amylin) and cholecystokinin (CCK) in awake, unrestrained rats with gastric cannulas. The experimental group underwent subdiaphragmatic vagal deafferentation; the control group had sham operations. All rats received 20-min intravenous infusions of IAPP (1, 3, 9, 27, and 81 pmol/kg/min), CCK (3, 30 and 90 pmol/kg/min), and normal saline in random order. Gastric emptying of saline was measured by the phenol red method during the last 5 min of each infusion period. CCK dose-dependently inhibited gastric emptying in both the control and SDA animals. The inhibition of GE by CCK was significantly attenuated by SDA (p0.01). IAPP also inhibited gastric emptying dose-dependently, but the difference between the SDA and control groups was not significant. The current experiment, which used a different methodology than previous studies, provides support for the hypothesis that the inhibition of gastric emptying by CCK, but not by IAPP, is mediated partly by afferent vagal fibers.

Islet amyloid polypeptide (IAPP) is postulated to act as a hormonal signal from the pancreas to the brain to inhibit food intake and reduce adipose energy reserves. The present study compared the effects of chronic peripheral and chronic central administration of IAPP on food intake and meal pattern in rats. IAPP was administered subcutaneously (SC) for 7 days at doses of 0, 0.25, 2.5 and 25 pmol kg −1 min −1 using an osmotic minipump or administered centrally at doses of 0, 0.025, 0.25 and 2.5 pmol kg −1 min −1 using an osmotic minipump connected to an intracerebroventricular (ICV) catheter inserted into the third ventricle. Both SC and ICV infusion decreased total food intake dose-dependently. The minimal effective dose was 2.5 pmol IAPP kg −1 min −1 for SC administration and 0.25 pmol kg −1 min −1 for ICV infusion. The decrease in food intake produced by infusion of IAPP was mainly due to decreased meal size, although a significant decrease in meal number also occurred at the highest SC and ICV doses. SC administration produced a larger, more persistent decrease in food intake during the light period than in the dark period, while ICV infusion caused a larger, more persistent decrease during the dark period. The 10-fold difference in minimal effective doses indicates that ICV-administered IAPP acted primarily in the brain to inhibit food intake. The difference between the effects of IAPP on meal pattern with the two methods of administration suggests that IAPP does not act on the same target(s) when administered centrally as it does when it is administered peripherally.

group meets at six 3-day meetings. These takes place at the different universities where the mentors are working. To the fi rst course, which started in August 1999, participants were recruited from the Nordic and Baltic countries, to the second and 3rd courses participants from several northern European countries, including Germany, Switzerland, UK, France, and the Czech republic, were invited. Along with pancreatological education and leadership training the participants also plan and carry through scientifi c projects in network-based groups of 5–6 persons, guided by two mentors. This implies brain-storming for research ideas (fi rst meeting), implement ideas to research protocols, apply for ethical approval and funding, realise the projects and write a manuscript suitable for submission. The scientifi c projects also runs between the meetings and the aim is to fi nish the different projects during the two and a half years. This has, however, not always been possible. Some of the groups have thus continued and fi nished their projects outside the timeframe of the six meetings but still within the Pancreas 2000 network. This far, 13 different projects have been initiated and of these 5 have been accepted or published [1–5] and 4 have been, or will soon be, submitted [6–9] . One study of risk factors, predictors and course in ERCP-induced acute pancreatitis is ongoing and three of the initiated projects will probably not be completed. During the last decades the number of active scientists within pancreatology has decreased in Europe and the age of the active scientists has increased. To guarantee the future of clinical pancreatology and pancreatic research, the educational program ‘Pancreas 2000’ started in August 1999. This is a new concept for continuous collaboration between the university (Karolinska Institutet) and the pharmacological industry (Solvay Pharmaceuticals) with the purpose of creating an international network of physicians/scientists interested in pancreatology and thus to contribute to a positive development of European pancreatology. This is a true collaboration, scientifi c as well as economic, as the program is sponsored partly by the respective departments of the participants and partly by the industry. The program is designed to stimulate development in especially three areas: pancreatology, scientifi c thinking and group leadership. The program, of which the 3rd course now is running, has recruited 22–25 young physicians/scientists to each course. They work together with 10 senior pancreatologists, the mentors. The mentors are actively contributing to the lectures and discussions and, furthermore, to every meeting special guests (world leading pancreatologists) are also invited to give lectures. Associated to the program is one leadership expert, who participates in every meeting, and a statistician. One program runs over two and a half years during which the Published online: August 18, 2005

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.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.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.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.

Background & aim : Little is known about the perspectives that patients with advanced cancer and their family members have concerning nutritional problems and nutritional support. The aim of this study was to investigate their experiences of the nutritional situation prior to introduction of home parenteral nutrition (HPN) in order to understand factors contributing to the decision to accept HPN. Methods : Semi-structured interviews were conducted with 13 patients with advanced cancer who had received HPN and 11 family members. The constant comparative method was used for data analysis. Results : Patients and family members described the nutritional situation prior to HPN as a source of worry and often desperation. Patients reported wanting and trying to eat, but being unable to do so. Family members experienced powerlessness and frustration, as they could not enable the patient to eat. A lack of attention to nutritional problems by the hospital staff was described. The offer of HPN came when patients and family no longer felt able to solve the nutritional problems within the family. Conclusion : The desperate and chaotic nutritional situation in the family led to willingness to accept HPN. Because of the severity of the problems, HPN was viewed as a positive alternative.

Objective Enteral feeding in the early postoperative phase may improve gut integrity and reduce infectious complications after trauma and surgery. The aim of the current study was to evaluate the feasibility of α-ketoglutarate enrichment of enteral feeding and the effect on protein metabolism after major surgery. Methods Patients undergoing elective abdominal surgery were randomly allocated to receive a standard whole-protein–based enteral nutrition solution ( n = 9) or an isonitrogenous, isocaloric solution enriched with α-ketoglutarate ( n = 11) for 5 d postoperatively. The nutritional goals by day 4 were 25 kcal and 0.17 g of nitrogen, respectively, per kilogram of body weight every 24 h. Standard blood analysis, including prealbumin and C-peptide, was performed preoperatively and on days 1, 3, and 6. Urine was collected daily for nitrogen and 3-methylhistidine analyses. Results Due to restricted tolerance to enteral feeding, the nitrogen delivery reached only 0.10 g of nitrogen per kilogram of body weight. Transthyretin decreased by 25% in both groups, and albumin decreased significantly in the enriched group compared with the standard nutrition. There were no significant differences in nitrogen balance, excretion of 3-methylhistidine, or clinical outcome between groups. Conclusions Enrichment of a whole-protein–based formula with α-ketoglutarate did not improve protein metabolism or decrease muscle catabolism after major abdominal surgery.