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Hypertriglyceridemia (HTG) is a metabolic disorder, defined when serum or plasma triglyceride concentration (seTG) is >1.7 mM. HTG can be categorized as mild to very severe groups based on the seTG value. The risk of acute pancreatitis (AP), a serious disease with high mortality and without specific therapy, increases with the degree of HTG. Furthermore, even mild or moderate HTG aggravates AP initiated by other important etiological factors, including alcohol or bile stone. This review briefly summarizes the pathophysiology of HTG, the epidemiology of HTG‐induced AP and the clinically observed effects of HTG on the outcomes of AP. Our main focus is to discuss the pathophysiological mechanisms linking HTG to AP. HTG is accompanied by an increased serum fatty acid (FA) concentration, and experimental results have demonstrated that these FAs have the most prominent role in causing the consequences of HTG during AP. FAs inhibit mitochondrial complexes in pancreatic acinar cells, induce pathological elevation of intracellular Ca2+ concentration, cytokine release and tissue injury, and reduce the function of pancreatic ducts. Furthermore, high FA concentrations can induce respiratory, kidney, and cardiovascular failure in AP. All these effects may contribute to the observed increased AP severity and frequent organ failure in patients. Importantly, experimental results suggest that the reduction of FA production by lipase inhibitors can open up new therapeutic options of AP. Overall, investigating the pathophysiology of HTG‐induced AP or AP in the presence of HTG and determining possible treatments are needed. [ABSTRACT FROM AUTHOR]

Objective To identify early available predictors for the long-term outcome of patients after transsphenoidal surgery (TSS) in the management of Cushing's disease. Methods This single-center, retrospective study included 93 consecutive patients with Cushing's disease (follow-up 12–129 months, mean 48, median 38) who underwent TSS (21 had previous operations elsewhere). Six cases had early re-operation, and the resulting data were evaluated instead of the respective first operation. During the postoperative course, serum cortisol levels were assessed every four hours at least until the next morning. An association of parameters with long-term outcomes was tested using binary logistic regression. Receiver operating characteristic curves were used to determine sensitivity, specificity, positive predictive value, and negative predictive value of different cut-off values of serum cortisol in the postoperative course in the event of recurrence after remission. Results Eighty out of 93 patients (86%) showed postoperative remission (after primary treatment, 60 out of 72 patients, 90.3%). Of these, 8 patients (10%) developed recurrence of hypercortisolism. Compared to patients with persisting long-term remission, those with recurrence differed in cortisol levels starting from 4 pm on the day of surgery plus an event of increasing cortisol during the early postoperative course ("peak"). Binary logistic regression showed the association between a peak of serum cortisol in the early postoperative course with an increased probability of recurrence. Conclusions Patients with a peak of serum cortisol in the early postoperative course show an increased recurrence rate. A cut-off value of serum cortisol for clear identification of patients with later recurrence could not be determined. [ABSTRACT FROM AUTHOR]

Background: Inflammation increases diabetes mellitus type 2 (T2DM) progression and severity. T2DM patients are at high risk of the rapid development of chronic periodontitis (CP). Topical presence, high numbers, and bactericidal effects of immune cells are challenged by augmented antigen‐induced inflammation, which promotes both diseases. Objectives: To investigate gingival cellular inflammatory responses in individuals with previously undiagnosed T2DM with CP or CP alone and in systemically and periodontally healthy controls (H) in vivo and to establish an ex vivo technique permitting quantitative and qualitative assessments of gingival crevicular immune cells. Materials and Methods: T2DM + CP, CP, and H individuals (n = 10, each) received a 2‐week oral hygiene regimen (OHR). Afterwards, a noninvasive sampling technique was performed to evaluate gingival inflammation induced under standardized conditions in vivo, that is, in the absence of severe periodontal destruction and inflammation at clinically healthy sites. Stimuli (casein/test or phosphate‐buffered saline w/o. Ca2+ or Mg2+, PBS(−/−)/control) were randomly applied contralaterally in the gingival sulci of participants' upper dentes canini. One day after completion of the OHR, gingival crevicular fluid (GCF) was kinetically assayed between the time of the baseline (BL) measurement and 55 minutes. Polymorphonuclear leukocyte (PMN) content (PMNGCF) was quantitated at an optimum time of 35 minutes. PMNGCF counts reflect local inflammation. Ex vivo samples were fluorimetrically labeled, gated according to the donor's peripheral blood polymorphonuclear neutrophils (PMNPB), and then counted, employing flow cytometry. Results: PMNGCF counts in unstimulated gingival crevices (at BL) in the T2DM + CP group were higher than those in the CP and H groups. PMNGCF counts were elevated in casein vs PBS(−/−)‐stimulated gingival crevices in all groups. Patients with T2DM + CP showed increased PMNGCF counts compared to those with CP (P =.035) according to scatter plots. CD45+ counts in the stimulated sites in T2DM + CP patients were higher than those in CP and H patients (P =.041). Under stimulation conditions, the CD45+ counts differed from those under placebo conditions (P =.019), indicating augmented, inducible inflammatory leukocyte infiltrate in T2DM + CP patients. Conclusions: This noninvasive technique permits quantitative assessment of (experimental) gingival inflammation in vivo, revealing an influence of T2DM + CP on the number of primary immune cells in the gingival crevice. Patients who are challenged with (local) leukocytosis are likely at risk of collateral damage to the gingival crevice neighboring tissues, favoring the severity and progression of CP and consequently T2DM (www.clinicaltrials.gov NCT01848379). [ABSTRACT FROM AUTHOR]

Abstract Background In collaboration with United European Gastroenterology, the working group on 'Harmonizing diagnosis and treatment of chronic pancreatitis across Europe' (HaPanEU) developed European guidelines for the management of chronic pancreatitis using an evidence-based approach. Methods Recommendations of multidisciplinary review groups based on systematic literature reviews to answer predefined clinical questions are summarised. Recommendations are graded using the Grading of Recommendations Assessment, Development and Evaluation system. Results Recommendations covered topics related to the clinical management of chronic pancreatitis: aetiology, diagnosis of chronic pancreatitis with imaging, diagnosis of pancreatic exocrine insufficiency, surgical therapy, medical therapy, endoscopic therapy, treatment of pancreatic pseudocysts, pancreatic pain, nutrition and malnutrition, diabetes mellitus and the natural course of the disease and quality of life. Conclusions The HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects of the medical and surgical management of chronic pancreatitis based on current available evidence. These recommendations should serve as a reference standard for existing management of the disease and as a guide for future clinical research. This article summarises the HaPanEU recommendations and statements. [ABSTRACT FROM AUTHOR]

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Hypertriglyceridemia is a well established cause of acute pancreatitis and accounts for up to 10% of all acute pancreatitis cases and even up to 50% of all acute pancreatitis cases in pregnancy. Hydrolysis of triglycerides by pancreatic lipase and excessive formation of free fatty acids with inflammatory changes, capillary injury and hyperviscosity are postulated to account for the development of hypertriglyceridemia-induced pancreatitis (HTGP). The clinical features of those patients are generally no different from patients with acute pancreatitis of other etiologies. HTGP, however, seems to be associated with a higher severity and complication rate. There is no clear evidence as to which hypertriglyceridemia patients will develop acute pancreatitis and which will not. Insulin, heparin, plasmapheresis and different antihyperlipidemic agents, as well as dietary modifications, are key features in the management of HTGP. [ABSTRACT FROM AUTHOR]

Hypertriglyceridemia is associated with a number of severe diseases such as acute pancreatitis and coronary artery disease. In severe hypertriglyceridemia (SHTG, triglycerides > 1,000 mg/dL), rapid lowering of plasma triglycerides (TG) has to be achieved. Treatment regimes include nutritional intervention, the use of antihyperlipidemic drugs, and therapeutic apheresis. Apheretic treatment is indicated in medical emergencies such as hypertriglyceridemic pancreatitis. Reviewing the current literature, plasmapheresis appears to be a safe and useful therapeutic tool in patients suffering from SHTG. Apheretic treatment is able to remove the causative agent for pancreatic inflammation. Data suggests that the use of apheresis should be performed as early as possible in order to achieve best results. The use of plasmapheresis, however, is limited due to the rather high costs and the limited availability of the procedure. [ABSTRACT FROM AUTHOR]

Pancreatic exocrine insufficiency is a frequently observed phenomenon in type 1 and type 2 diabetes mellitus. Alterations of exocrine pancreatic morphology can also be found frequently in diabetic patients. Several hypotheses try to explain these findings, including lack of insulin as a trophic factor for exocrine tissue, changes in secretion and/or action of other islet hormones, and autoimmunity against common endocrine and exocrine antigens. Another explanation might be that diabetes mellitus could also be a consequence of underlying pancreatic diseases (e.g., chronic pancreatitis). Another pathophysiological concept proposes the functional and morphological alterations as a consequence of diabetic neuropathy. This paper discusses the currently available studies on this subject and tries to provide an overview of the current concepts of exocrine pancreatic insufficiency in diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: Patients with highly increased plasma triglyceride levels are at risk of developing serious complications such as pancreatitis, coronary heart disease and stroke. Therefore it is important to rapidly decrease plasma triglyceride levels. A sufficient control of triglyceride levels with drugs like fibrates, statins or nicotinic acid can usually only be attained after a couple of weeks. Plasma exchange appears to be a fast but expensive method to reduce triglyceride levels. In this study we describe the use of a new ω–3 fatty acid and medium-chain triglyceride-rich formula diet as a therapeutic concept to reduce plasma triglyceride levels fast and effectively. Methods: Thirty-two patients with severe hypertriglyceridemia were treated with the especially composed formula diet for a period of 7 days. Results: Within this period of time, plasma triglycerides decreased from 1,601 (402–4,555) to 554 (142–2,382) mg/dl (p < 0.05). Total cholesterol levels were reduced from 417 (211–841) to 287 (165–457) mg/dl (p < 0.001). Fasting glucose and uric acid levels also slightly decreased (–8%; –12%). The formula diet as a 1-week treatment was well tolerated and accepted by the patients. Conclusion: This diet was successfully used as an acute treatment in severe hypertriglyceridemia and showed effectiveness in rapidly and safely lowering plasma triglyceride levels. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Proliferating cells, in particular tumor cells, express a dimeric isoenzyme of pyruvate kinase, termed Tumor M2 pyruvate kinase. In the last few years, much attention has been paid to this novel tumor marker that can be determined in EDTA-plasma and in the feces. It has been used in diagnosis and surveillance of a variety of malignant diseases. As compared with the established tumor markers, Tumor M2 PK in EDTA plasma proves to have at least equal sensitivity in pancreatic, gastric, esophageal, colorectal and cholangiocellular cancer. In combination with established tumor markers, EDTA plasma M2 PK is a useful tool in diagnosis and surveillance of gastrointestinal tumors In colorectal cancer, M2 PK in EDTA plasma even proves superiority as compared with CEA. Fecal Tumor M2 PK testing resembles a good noninvasive screening parameter for colorectal cancer with a reported sensitivity of 68.8-91.0% and a specificity of 71.9-100%. It is superior to fecal occult blood testing in colorectal cancer screening. Since it is effective, easy to handle and bears rather low costs, fecal Tumor M2-PK testing is recommended for large scale CRC screening. [ABSTRACT FROM AUTHOR]

Background/Aims: Successful treatment of severe hypertriglyceridemia is difficult. Besides therapy with different drugs, dietary intervention is an important approach. However, compliance with dietary recommendations is usually bad. Lipid self-monitoring in patients might improve dietary compliance and control of lipid parameters. Methods: Thirty-two patients with severe hypertriglyceridemia (>750 mg/dl) were primarily treated with a formula diet reducing the triglyceride levels <600 mg/dl. After this acute treatment, self-monitoring of lipid parameters was performed for 48 weeks. Twenty-five patients completed the whole study. The participants measured their lipid parameters with Accutrend® GCT dry chemistry strips. Dietary records were taken and measurements of body composition, BMI, triglycerides, total cholesterol and glucose were performed. Results: Triglycerides remained stable in patients with levels <300 mg/dl at the beginning of the protocol. There was a significant decline in triglycerides in those who started with levels >300 mg/dl. No severe hypertriglyceridemia (>750 mg/dl) could be observed. The energy intake decreased in all patients due to a reduction in total fat and carbohydrate consumption. The relation between carbohydrates and protein remained unchanged. Self-measurement was well tolerated and an improvement in controlling the diet was reported. Conclusions: Self-control of lipid parameters can improve the dietary compliance of patients with hypertriglyceridemia and is well tolerated. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background Recently, high prevalence of exocrine dysfunction in diabetic populations has been reported. Patients with fecal elastase 1 concentration (FEC) <100 µg/g have also been demonstrated to suffer from steatorrhea in about 60% of cases, indicating the need of pancreatic enzyme replacement therapy. Until now, there have only been a few reports on the use of enzyme replacement therapy in diabetic patients with exocrine pancreatic insufficiency. This investigation was designed to evaluate the impact of enzyme-replacement therapy on glucose metabolism and diabetes treatment in a prospective study of insulin-treated patients with diabetes mellitus. Methods A total of 546 patients with diabetes mellitus requiring insulin treatment were screened for exocrine dysfunction by FEC measurements. One hundred and fifteen patients (21.1%) had FEC <100 µg/g (normal >200 µg/g). Of these, 95 patients entered the study and 80 patients were randomized to receive either pancreatin (Creon®) (39 patients) or placebo (41 patients) in a double-blind manner. Parameters of glucose metabolism, diabetes therapy and clinical symptoms were recorded in standardized protocols for 16 weeks. Results During the observation phase of 16 weeks, there were no significant differences between both groups concerning HbA1c, fasting glucose levels, 2-h pp glucose levels, clinical parameters and safety parameters. A reduction in mild and moderate hypoglycemia was observed in the pancreatin group at the end of the study. Conclusions Pancreatin therapy can be used safely in patients with diabetes mellitus and exocrine dysfunction. Parameters of glucose metabolism were not improved by enzyme replacement therapy. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The overwhelming post splenectomy infection (OPSI) in splenectomised patients is a rare but severe infection mostly caused by encapsulated bacteria. We analyse the case of a 65-year-old female patient who was presented with clinical and laboratory findings indicating gastroenteritis. Two years years before admission, the patient underwent a splenectomy for a two stage splenic rupture following resuscitation for pulmonary embolism. Immunisation of the patient was complete and timely. As a result of the unspecific clinical presentation, there was a delay in administration of antibiotics. However, administration of antibiotics induced a fulminant shock. The patient died 4 hours after attending the hospital due to a pneumococcal sepsis. The discussion highlights epidemiological and pathophysiological aspects and potential prevention strategies in the international context. Vaccination failed in our patient as the isolated pneumococcal strain (serogroup: 12F) is usually covered by the 23-valent pneumococcal polysaccharide vaccination (Pneumovax(®)). The case reported here indicates that there may be a potential benefit of prophylactic antibiotic treatment within the first 3 years after splenectomy for patients above the age of 65 years. Awareness of OPSI (prevention strategies, symptoms and treatment) among patients and their treating physicians is crucial for the improvement of prognosis. We partly address these issues in a standard operating procedure for the assessment of splenectomised patients in our departments of emergency medicine. [ABSTRACT FROM AUTHOR]