[Epidemiology and surgical treatment of pancreatic cancer in the State of Brandenburg : Analysis of 5418 cases]. / Epidemiologie und operative Behandlung des Pankreaskarzinoms im Flächenland Brandenburg : Analyse von 5418 Fällen.

BACKGROUND: Pancreatic cancer is the second most frequent cause of death among all forms of cancer in Germany with more than 19,000 deaths per year. The evaluation of the nationwide clinical cancer register aims to depict the reality of treatment and to improve the quality of treatment in the future by targeted analyses. METHOD: The data from the clinical cancer register of Brandenburg-Berlin for the diagnosis years 2001-2017 were analyzed with respect to the treatment of pancreatic cancer. Data from patients resident in the State of Brandenburg were evaluated with respect to epidemiological and therapeutic parameters. RESULTS: A total of 5418 patients with pancreatic cancer were documented in the register from 2001 to 2017 and 49.6% of the patients were diagnosed as having the Union for International Cancer Control (UICC) stage IV. A pancreas resection was carried out in 26.4% of the cases. In cases of cancer of the head of the pancreas the most frequent procedure was a pylorus-preserving resection with 51.8% and a pancreatectomy was carried out in 9.4%. The R0 resection rate of all pancreatic cancers in the period from 2014 to 2017 was 61.9%. After R0 resection the 5­year survival was 19%. Relevant multivariate survival factors were age, UICC stage and the residual (R) tumor classification. The case numbers per hospital had no influence on the absolute survival of patients operated on in the State of Brandenburg. CONCLUSION: The treatment reality in the State of Brandenburg for patients with pancreatic cancer corresponds to the results of international publications with respect to the key performance indicators investigated. A qualitative internationally comparable treatment of these patients is also possible in nonmetropolitan regions.

Effect of different lipid apheresis methods on plasma polyunsaturated fatty acids.

Lipoprotein apheresis has been shown to improve the cardiovascular outcome in patients with atherosclerotic disease and therapy-refractory hypercholesterolemia or elevated lipoprotein (a) (Lp(a)). An elevated intake of omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has also been associated with a reduced cardiovascular risk. However, until now only little is known about the effect of apheresis treatment on the levels of omega-6 and omega-3 polyunsaturated fatty acids (n-6 PUFA and n-3 PUFA) in patients. Using gas chromatography (GC) the present study analyzed the content of n-6 and n-3 PUFA as well as saturated fatty acids and monounsaturated fatty acids in the plasma of 20 patients with hyperlipidemia undergoing regular lipoprotein apheresis procedures in direct pre- and post-therapy measurements. Lipoprotein apheresis uniformly reduced the concentrations of arachidonic acid (AA), EPA and DHA fatty acids analyzed in the plasma. However, the three different apheresis methods analyzed (heparin precipitation, membrane filtration and direct absorption) had different effects on the fatty acid profile in the plasma. We found that heparin precipitation and direct absorption apheresis procedures led to a significant decrease of plasma n-3 and n-6 PUFA by 40-50%. In contrast, patients undergoing membrane filtration apheresis, levels pre- and post-apheresis did not change significantly, with AA and EPA being only reduced by approximately 10% while levels of DHA were maintained pre- and post-apheresis. In contrast, total triglyceride levels were lowered most potently by membrane filtration apheresis. In summary, heparin precipitation and direct absorption apheresis approaches significantly lowered polyunsaturated fatty acids in plasma, while membrane filtration did not. This might have implications for cardiovascular and inflammatory risk/benefit profiles associated with n-6 and n-3 PUFA levels in the body.

A lipidomic analysis approach in patients undergoing lipoprotein apheresis.

Lipoprotein apheresis such as heparin-induced extracorporal LowDensityLipoprotein (LDL) Cholesterol precipitation (HELP) reduces apolipoprotein B-containing lipoproteins, most importantly low-density-lipoprotein (LDL), and lipoprotein (a) [Lp(a)]. It is used in patients with atherosclerotic disease and therapy-refractory hypercholesterolemia or progressive atherosclerotic disease in patients with elevated Lp(a). While lipid-lowering effects of lipoprotein apheresis are well-established, there are only sparse data regarding the effect of apheresis on individual omega-6 and omega-3 polyunsaturated fatty acids (n-6 PUFA and n-3 PUFA), such as arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which could increase (AA) or decrease (EPA and DHA) cardiovascular risk. Here we analyzed different omega-6 and omega-3 fatty acids in the blood of patients undergoing a single HELP apheresis procedure using gas chromatography (GC). Furthermore, we assessed the effect of HELP treatment on formation of lipid metabolites and mediators arising from these polyunsaturated fatty acids in the plasma by LC/ESI-MS/MS. Lipoprotein apheresis reduced the concentrations of fatty acids analyzed in the plasma by 40-50%. This was similar for AA, EPA and DHA. The reduction in fatty acid plasma levels was similar to the reduction of total triglycerides. However there was a trend towards an increase of PUFA metabolites associated with platelet activation, such as 12-hydroxyeicosatetraenoic acid (12-HETE) and 14-hydroxydocosahexaenoic acid (14-HDHA). These data indicate that HELP apheresis could interfere with achieving higher levels of n-3 PUFA in the plasma. Lipid apheresis treatment might also increase the formation of potentially pro- as well as anti-inflammatory lipid mediators derived from AA or EPA and DHA.

Human ClC-3 is not the swelling-activated chloride channel involved in cell volume regulation.

Volume regulation is essential for normal cell function. A key component of the cells' response to volume changes is the activation of a channel, which elicits characteristic chloride currents (I(Cl, Swell)). The molecular identity of this channel has been controversial. Most recently, ClC-3, a protein highly homologous to the ClC-4 and ClC-5 channel proteins, has been proposed as being responsible for I(Cl, Swell). Subsequently, however, other reports have suggested that ClC-3 may generate chloride currents with characteristics clearly distinct from I(Cl, Swell). Significantly different tissue distributions for ClC-3 have also been reported, and it has been suggested that two isoforms of ClC-3 may be expressed with differing functions. In this study we generated a series of cell lines expressing variants of ClC-3 to rigorously address the question of whether or not ClC-3 is responsible for I(Cl, Swell). The data demonstrate that ClC-3 is not responsible for I(Cl, Swell) and has no role in regulatory volume decrease, furthermore, ClC-3 is not activated by intracellular calcium and fails to elicit chloride currents under any conditions tested. Expression of ClC-3 was shown to be relatively tissue-specific, with high levels in the central nervous system and kidney, and in contrast to previous reports, is essentially absent from heart. This distribution is also inconsistent with the previous proposed role in cell volume regulation.

Polyunsaturated fatty acids exert antiarrhythmic actions as free acids rather than in phospholipids.

Previous studies have shown that exogenous free n-3 polyunsaturated fatty acids (PUFA) can prevent tachyarrhythmias caused by specific agents in isolated cardiac myocytes. However, the question as to whether incorporation of the n-3 PUFA into membrane phospholipids has the same immediate protective effects remained to be answered. To answer this question, we increased the content of n-3 PUFA in the phospholipids of cultured neonatal rat myocytes by growing them 2-3 d in a culture to which eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) in 15 microM concentration was added. Analysis of the fatty acid composition of membrane phospholipids revealed a significantly higher level of EPA and DHA (from 0.2 to 7.6% and from 1.2 to 6.5%) in cells supplemented with EPA or DHA, respectively. The responses of the myocytes grown in normal media or in media enriched with the PUFA to arrhythmogenic agents were examined after free fatty acids were removed from the medium and the cells. The arrhythmogenic agents used were the beta-adrenergic agonist isoproterenol or an elevated extracellular concentration of calcium. The results showed that there was no significant difference in the induction of tachyarrhythmias by isoproterenol or by elevated [Ca2+]o in cells grown in media enriched with PUFA, as compared with cells grown in normal media in the absence of the free PUFA. Under the conditions of this study, only the unesterified PUFA were able to protect the cardiomyocytes against induced arrhythmias. There was no antiarrhythmic effect due to an increased fraction of EPA or DHA in membrane phospholipids.