The presence of the proteolysis-inducing factor in urine does not predict the malignancy of a pancreatic tumour

BACKGROUND: The proteolysis-inducing factor (PIF) was identified as a tumour product in various gastrointestinal cancers. A previous study in pancreatic cancer patients suggested PIF expression as a tumour marker, which is not related to tumour size. We hypothesized that PIF could be a useful marker to exclude benign pancreatic tumors, as chronic pancreatitis with a pancreatic mass. METHODS: Urine of patients with a pancreatic mass of uncertain malignancy was investigated for PIF expression by Western blot. Sufficient urine protein for analysis was available in 59 patients. The diagnosis was established by histology in 54 patients and by follow up in five patients with chronic pancreatitis. In addition, serum CA19-9 was measured. RESULTS: The sensitivity (specifity) for the detection of a malignant pancreatic tumour was 90% (75%) and 54% (71%) for CA19-9 and PIF, respectively. The sensitivity (specifity) for the distinction of pancreatic cancer from chronic pancreatitis was 89% (80%) and 57% (63%) for CA19-9 and PIF, respectively. CONCLUSION: Evaluation of PIF in urine is of no diagnostic value in patients with a pancreatic mass of unknown malignancy

Plasma bile acids are not associated with energy metabolism in humans

Bile acids (BA) have recently been shown to increase energy expenditure in mice, but this concept has not been tested in humans. Therefore, we investigated the relationship between plasma BA levels and energy expenditure in humans. Type 2 diabetic (T2DM) patients (n = 12) and gender, age and BMI-matched healthy controls (n = 12) were studied before and after 8 weeks of treatment with a BA sequestrant. In addition, patients with liver cirrhosis (n = 46) were investigated, since these display elevated plasma BA together with increased energy expenditure. This group was compared to gender-, age- and BMI-matched healthy controls (n = 20). Fasting plasma levels of total BA and individual BA species as well as resting energy expenditure were determined. In response to treatment with the BA sequestrant, plasma deoxycholic acid (DCA) levels decreased in controls (-60%, p &lt;0.05) and T2DM (-32%, p &lt;0.05), while chenodeoxycholic acid (CDCA) decreased in controls only (-33%, p &lt;0.05). Energy expenditure did not differ between T2DM and controls at baseline and, in contrast to plasma BA levels, was unaffected by treatment with the BA sequestrant. Total BA as well as individual BA species did not correlate with energy expenditure at any time throughout the study. Patients with cirrhosis displayed on average an increase in energy expenditure of 18% compared to values predicted by the Harris-Benedict equation, and plasma levels of total BA (up to 12-fold) and individual BA (up to 20-fold) were increased over a wide range. However, neither total nor individual plasma BA levels correlated with energy expenditure. In addition, energy expenditure was identical in patients with a cholestatic versus a non-cholestatic origin of liver disease while plasma total BA levels differed four-fold between the groups. In conclusion, in the various (patho) physiological conditions studied, plasma BA levels were not associated with changes in energy expenditure. Therefore, our data do not support an important role of circulating BA in the control of human energy metabolism.</p

European guideline on obesity care in patients with gastrointestinal and liver diseases - Joint European Society for Clinical Nutrition and Metabolism / United European Gastroenterology guideline

Background Patients with chronic gastrointestinal (GI) disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean GI patients. The present guideline addresses this question according to current knowledge and evidence. Objective The objective of the guideline is to give advice to all professionals working in the field of gastroenterology care including physicians, surgeons, dietitians and others how to handle patients with GI disease and obesity. Methods The present guideline was developed according to the standard operating procedure for European Society for Clinical Nutrition and Metabolism guidelines, following the Scottish Intercollegiate Guidelines Network grading system (A, B, 0, and good practice point [GPP]). The procedure included an online voting (Delphi) and a final consensus conference. Results In 100 recommendations (3x A, 33x B, 24x 0, 40x GPP, all with a consensus grade of 90% or more) care of GI patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially fatty liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. Conclusion The present guideline offers for the first time evidence-based advice how to care for patients with chronic GI diseases and concomitant obesity, an increasingly frequent constellation in clinical practice

ESPEN guideline on clinical nutrition in acute and chronic pancreatitis

Both acute and chronic pancreatitis are frequent diseases of the pancreas, which, despite being of benign nature, are related to a significant risk of malnutrition and may require nutritional support. Acute necrotizing pancreatitis is encountered in 20% of patients with acute pancreatitis, is associated with increased morbidity and mortality, and may require artificial nutrition by enteral or parenteral route, as well as additional endoscopic, radiological or surgical interventions. Chronic pancreatitis represents a chronic inflammation of the pancreatic gland with development of fibrosis. Abdominal pain leading to decreased oral intake, as well as exocrine and endocrine failure are frequent complications of the disease. All of the above represent risk factors related to malnutrition. Therefore, patients with chronic pancreatitis should be considered at risk, screened and supplemented accordingly. Moreover, osteoporosis and increased facture risk should be acknowledged in patients with chronic pancreatitis, and preventive measures should be considered

Molekulare Mechanismen von Pankreaserkrankungen

Die Ätiologie von entzündlichen Pankreaserkrankungen, insbesondere bei den idiopathischen Pankreatitiden, ist weitgehend noch nicht verstanden. In der folgenden Arbeit sollen immunologische und molekularbiologische Aspekte zu Pankreaserkrankungen unter Berücksichtigung eigener Untersuchungen dargestellt werden. Zu Beginn unserer Arbeit haben wir untersucht inwieweit immunologische Veränderungen an der Entstehung einer chronischen Pankreatitis beteiligt sind. Wir fanden eine systemische Aktivierung des zellulären Immunsystems, ohne dass sich Unterschiede zwischen idiopathischer und alkoholtoxischer Pankreatitis ergaben. Im folgenden haben wir uns mit dem molekularbiologischen Hintergrund von entzündlichen und malignen Pankreaserkrankungen beschäftigt. Eine genetische Modellerkrankung ist die hereditäre Pankreatitis, deren genetische Ursache 1996 mit der Entdeckung zweier Mutationen im kationischen Trypsinogen entschlüsselt wurde. Mit der Identifizierung einer neuen Mutation im kationischen Trypsinogen und deren funktionellen Charakterisierung konnten wir hier zum weiteren Verständnis dieser Erkrankung beitragen. Weitere Untersuchungen beschäftigten sich mit dem genetischen Hintergrund bei Patienten mit idiopathischer Pankreatitis. Bei etwa 30% dieser Patienten fanden wir ein abnormales Allel im Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gen und bei einzelnen Patienten einen Polymorphismus im Serine Proteasen Inhibitor (SPINK1) Gen. Das zunehmende Wissen um genetische Veränderungen und deren Folgen setzt auch eine kritische Auseinandersetzung mit ethischen und rechtlichen Fragen voraus. Daher wurden während einer internationalen Konsensus Konferenz Richtlinien zum Umgang mit diesen Fragen erarbeitet. Die Assoziation von UGT1A7*3 Polymorphismus, welches ein Phase II Protein mit niedriger katalytischer Entgiftungsaktivität im Xenobiotika Stoffwechsel kodiert, mit dem Auftreten von Pankreaserkrankungen war Gegenstand weiterer Untersuchungen. Hierzu untersuchten wir Patienten mit alkoholischer chronischer Pankreatitis, Patienten mit einer SPINK1 Mutation und gesunde Kontrollen. Darüberhinaus betrachteten wir ein Kollektiv von Patienten mit einem Pankreaskarzinom. Unsere Ergebnisse belegen einen synergistischen negativen Effekt von exogenen Risikofaktoren (Alkohol, Nikotin) und genetischer Prädisposition. Die Rolle des oxidativen Stresses in der Genese von Pankreaserkrankungen wird damit untermauert. Erste therapeutische Ansätze aus den gewonnenen Erkenntnisses haben wir in einer prospektiven Studie mit einer immunmodulierenden und antioxidativ wirksamen Glutaminsubstitution bei Patienten mit akuter Pankreatitis gezeigt. Die Glutaminsubstitution führte zu einem besseren Krankheitsverlauf.The etiology of inflammatory and malignat pancreatic disease are poorly understood. This thesis will discuss our results of immunological and genetic investigations in patients with inflammatory and malignat pancreatic diseases. Especially the background of idiopathic pancreatitis will be discussed. We started our investigations with immunological investigations and demonstrated an evidence for a systemic activated cellular immune system in patients with chronic pancreatitis irrespectively of the aetiology of pancreatitis. Further studies deal with the genetic background of pancreatitis. The discovery of the association between a mutation of the cationic trypsinogen gene and the hereditary pancreatitis was a milestone in the modern pancreatology. We contribute to the understanding of this disease by detecting a new mutation (D22G). We were able to functional characterise this mutation. Mutation of the activation peptides (D22G, K23R) are related to an increased release of trypsin in hydrolisation studies in vitro. In addition, our further investigations confirmed and extended the knowledge of the role of mutation in the CFTR gene and the SPINK 1 gene in patients with 'idiopathic' pancreatitis. Cognisant of the ethical and clinical responsibilities guidelines for the genetic testing and managing of patients with genetic diseases of the pancreas were developed. The low detoxification activity UGT1A7*3 polymorphism has been identified as a novel risk factor of pancreatic inflammatory and malignant diseases defining the interaction of genetic predisposition and environmentally induced oxidative injury. Based on this data we conducted a prospective, randomised clinical trial on the supplementation with glutamine in patients with acute pancreatitis shedulded for total parenteral nutrition. The administration of glutamine, which has been shown to have an immune-modulating and antioxidative capacity, was associated with a favourable clinical course of the patiens receiving glutamine

Elevated resistin levels in cirrhosis are associated with the proinflammatory state and altered hepatic glucose metabolism but not with insulin resistance

The adipokine resistin has been implicated in obesity and insulin resistance. Liver cirrhosis is associated with decreased body fat mass and insulin resistance. We determined plasma resistin levels in 57 patients with cirrhosis, 13 after liver transplantation, and 30 controls and correlated these with hemodynamic as well as hepatic and systemic metabolic parameters. Patients with cirrhosis had, dependent on the clinical stage, an overall 86% increase in resistin levels (P <0.001) with hepatic venous resistin being higher than arterial levels (P <0.001). Circulating resistin was significantly correlated with plasma TNF-alpha levels (r = 0.62, P <0.001). No correlation was observed between resistin and hepatic hemodynamics, body fat mass, systemic energy metabolism, and the degree of insulin resistance. However, plasma resistin in cirrhosis was negatively associated with hepatic glucose production (r = -0.47, P <0.01) and positively with circulating free fatty acids (FFA; r = 0.40, P <0.01) and ketone bodies (r = 0.48, P <0.001) as well as hepatic ketone body production (r = 0.40, P <0.01). After liver transplantation, plasma resistin levels remained unchanged, whereas insulin resistance was significantly improved (P <0.01). These data provide novel insights into the role of resistin in the pathophysiological background of a catabolic disease in humans and also indicate that resistin inhibition may not represent a suitable therapeutic strategy for the treatment of insulin resistance and diabetes in patients with liver cirrhosis