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Metabolic dysfunctions after pancreatoduodenectomy (PD) need to be considered when pancreatic head resection is likely to lead to long-term survival.Medline, Embase and Cochrane Library were searched for studies reporting measured data of metabolic function after PD and duodenum-sparing total pancreatic head resection (DPPHR). Data from 23 cohort studies comprising 1019 patients were eligible; 594 and 910 patients were involved in systematic review and meta-analysis, respectively.The cumulative incidence of postoperative new onset of diabetes mellitus (pNODM) after PD for benign tumors was 46 of 321 patients (14%) measured after follow-up of in mean 36 months postoperatively. New onset of postoperative exocrine insufficiency (PEI) was exhibited by 91 of 209 patients (44%) after PD for benign tumors measured in mean 23 months postoperatively. The meta-analysis indicated pNODM after PD for benign tumor in 32 of 208 patients (15%) and in 10 of 178 patients (6%) after DPPHR (p = 0.007; OR 3.01; (95%CI:1.39-6.49)). PEI was exhibited by 80 of 178 patients (45%) after PD and by 6 of 88 patients (7%) after DPPHR (p 0.001). GI hormones measured in 194 patients revealed postoperatively a significant impairment of integrated responses of gastrin, motilin, insulin, secretin, PP and GIP (p 0.050-0.001) after PD. Fasting and stimulated levels of GLP-1 and glucagon levels displayed a significant increase (p 0.020/p 0.030). Following DPPHR, responses of gastrin, motilin, secretin and CCK displayed no change compared to preoperative levels.After PD, duodenectomy, rather than pancreatic head resection is the main cause for long-term persisting, postoperative new onset of DM and PEI.

Conflicting results have been published about the effects of carbon dioxide (CO 2 ) pneumoperitoneum on splanchnic and liver perfusion. Several experimental studies described a pressure-related reduction in hepatic blood flow, whereas other investigators reported an increase as long as the intraabdominal pressure (IAP) remained less than 16 mm Hg. Our goal in the present study was to investigate the effects of insufflated CO 2 on hepatic blood flow during laparoscopic surgery in healthy adults. Blood flow in the right and middle hepatic veins was assessed in 24 patients undergoing laparoscopic surgery by use of transesophageal Doppler echocardiography. Hepatic venous blood flow was recorded before and after 5, 10, 20, 30, and 40 min of pneumoperitoneum, as well as 1 and 5 min after deflation. Twelve patients undergoing conventional hernia repair served as the control group. The induction of pneumoperitoneum produced a significant increase in blood flow of the right and middle hepatic veins. Five minutes after insufflation of CO 2 the median right hepatic blood flow index increased from 196 mL/min/m 2 (95% confidence interval (CI), 140-261 mL/min/m 2 ) to 392 mL/min/m 2 (CI, 263-551 mL/min/m 2 ) (P < 0.05) and persisted during maintenance of pneumoperitoneum. In the middle hepatic vein the blood flow index increased from 105 mL/min/m 2 (CI, 71-136 mL/min/ m 2 ) to 159 mL/min/m 2 (CI, 103-236 mL/min/m 2 ) 20 min after insufflation of CO 2 . After deflation blood flow returned to baseline values in both hepatic veins. Conversely, in the control group hepatic blood flow remained unchanged over the entire study period. We conclude that induction of CO 2 pneumoperitoneum with an IAP of 12 mm Hg is associated with an increase in hepatic perfusion in healthy adults.

Oxidative stress is an important factor in the pathogenesis of acute pancreatitis, as shown in vivo by the beneficial effects of scavenger treatment and in vitro by the potential of free radicals to induce acinar cell damage. However, it is still unclear whether oxygen free radicals (OFR) act only as mediators of tissue damage or represent the initiating event in acute pancreatitis in vivo as well. In the present study the authors aimed to address this issue in an experimental set-up.Two hundred male Wistar rats were randomly assigned to one of the following experimental groups. In two groups, acute necrotizing pancreatitis was induced by retrograde intraductal infusion of 3% sodium taurocholate. Through the abdominal aorta, a catheter was advanced to the origin of the celiac artery for continuous regional arterial (CRA) pretreatment with isotonic saline (NP-S group) or superoxide dismutase/catalase (NP-SOD/CAT group). In another group, oxidative stress was generated by CRA administration of xanthine oxidase and intravenous administration of hypoxanthine (HX/XOD group). Sham-operated rats received isotonic saline both arterially and intraductally. After observation periods of 5 and 30 minutes and 3 and 6 hours, the pancreas was removed for light microscopy and determination of reduced glutathione (GSH), oxidized glutathione (GSSG), conjugated dienes (CD), and malondialdehyde as a marker for OFR-induced lipid peroxidation as well as myeloperoxidase as a parameter for polymorphonuclear leukocyte accumulation.A significant decrease of GSH was paralleled by an increased ratio of GSSG per total glutathione and elevated CD levels after 5 minutes in the NP-S group versus the sham-operated group. Thereafter, the percentage of GSSG and GSH returned to normal levels until the 6-hour time point. After a temporary decrease after 30 minutes, CD levels increased again at 3 hours and were significantly higher at 6 hours in contrast to sham-operated rats. Myeloperoxidase levels were significantly elevated at 3 and 6 hours after pancreatitis induction. In contrast to NP-S rats, treatment with SOD/CAT significantly attenuated the changes in glutathione metabolism within the first 30 minutes and the increase of CDs after 6 hours. HX/XOD administration lead to changes in levels of GSH, GSSG, and CDs at 5 minutes as well as to increased myeloperoxidase levels at 3 hours; these changes were similar to those observed in NP-S rats. Acinar cell damage including necrosis was present after 5 minutes in both NP groups, but did not develop in HX/XOD rats. In addition, serum amylase and lipase levels did not increase in the latter group. SOD/CAT treatment significantly attenuated acinar cell damage and inflammatory infiltrate compared with NP-S animals during the later time intervals.OFRs are important mediators of tissue damage. However, extracellular OFR generation alone does not induce the typical enzymatic and morphologic changes of acute pancreatitis. Factors other than OFRs must be involved for triggering acute pancreatitis in vivo.

Using a retrograde infusion sodium taurocholate pancreatitis model in the rat treatment with oxygen radical scavengers or monoclonal anti-ICAM-1 antibody decreased tissue damage and polymorphonuclear leukocytes (PMN) infiltration. Scavengers or anti-ICAM-1 treatment attenuated the activating capacity of blood PMNs following zymosan stimulation. The local production of oxygen free radicals in the pancreas by systemic infusion of hypoxanthine and regional infusion of xanthine oxidase did not induce acute pancreatitis, although an increase of infiltrating PMNs was observed. Our data suggest that oxygen free radicals and infiltrating PMNs aggravate acute pancreatitis and that both are important mediators of local destruction and systemic activation of PMNs.

We investigated the effects of endogenously produced and exogenously applied nitric oxide (NO) on cell proliferation rates and cell cycle regulation in senescent human fibroblasts (WI38). Induction of inducible nitric oxide synthase by tumor necrosis factor-alpha, interferon-gamma and interleukin-1beta inhibited cell proliferation and led to a G1 arrest. These effects were partially reversible by N(G)-monomethyl-arginine (NMA). Addition of the NO donors sodium nitroprusside (SNP) or S-nitroso-N-acetylpenicillamine (SNAP) increased cell proliferation rates as well as the S/G2 fraction. This points to a functional role of NO in cell cycle regulation and cell proliferation in human fibroblasts which depends on the mode of NO generation as well as the culture conditions used.

Background. Carcinoid tumors of the gastrointestinal tract are most common localized in the appendix, followed by the small intestine, the rectum, and the stomach. The localization of these tumors at the ampulla of Vater is extremely seldom. Methods. In the present study the authors describe two patients with carcinoid tumors of the ampulla Vater and review 71 previously published cases. Results. Most patients presented with jaundice, but without carcinoid syndrome. Because the tumor grows submucosally, preoperative diagnosis was correct only in 15%. Most tumors were around 2 cm in size. Metastasis to lymph nodes and/or liver was present in 45%. Standard treatment is Whipple resection or local excision in small tumors. Conclusions. Carcinoid tumors of the ampulla of Vater are an extremely rare clinical entity. Generally, the prognosis is good with a 5-year survival period of 90%.

Background/Aim : In spite of the interest in free radicals as mediators of ischemic damage, most information on these species in biological systems is derived from indirect measurements. Our aim was to obtain more direct information concerning sources of free radical production during ischemia and reperfusion. Methods : We have performed simultaneous measurement of radical generation, purine metabolites, reduced glutathione, neutrophil infiltration and morphological appearance in the cat small intestine in vivo during 60 minutes of ischemia followed by 60 minutes of reperfusion. Results : Radical formation increased abruptly on reperfusion and remained elevated in untreated animals. Inhibition by a monoclonal antibody (IB4) against the neutrophil and by allopurinol treatment was paralleled by improvement of biochemical and morphological parameters. The radicals detected during reperfusion could be divided into one component arising directly from the neutrophils, one due to the xanthine oxidase reaction, and one unknown source. Conclusions : Neutrophils are a major source of radical production during reperfusion after ischemia. Radicals formed in the xanthine oxidase reaction seem to function as a primer for the neutrophils. The nonsignificant linear correlation between radical formation and morphological appearance suggests that factors other than free radicals are important for the development of intestinal damage after a period of ischemia.

Cancers of the pancreas are identified in 11 800 to 13 500 patients each year in Germany (1). The mean age at disease onset is 68 years in men and 70 years in women. For some years, women have been observed to develop the disease more frequently than men (1). The growing incidence of pancreatic cancer in the industrialized countries is attributed to overweight (2), increasing age, smoking (4), and chronic alcohol consumption (4). Epidemiological studies have shown smoking to be the cause in about 30% of cases of ductal pancreatic cancer (3); pancreatic diseases with a markedly elevated risk of malignancy – besides the genetically determined syndromes with high pancreatic carcinoma penetrance (5) – are hereditary chronic pancreatitis with up to 40% malignancy (6), chronic alcoholic pancreatitis with 4% to 6 % malignancy (7), and cystic neoplasms with a malignant transformation rate of 20% to 70% (8). Pancreatic cancer is still incurable for more than 95% of patients (9). In preparation for exercising the function of expert (Beger), and as a member of the Surgical Treatment Working Group for drafting of the S3 guidelines of the German Society of Digestive and Metabolic Diseases (DGVS)/ of the Scientific Medical Societies in Germany (AWMF) (Rau), the authors conducted a selective literature review based on their clinical and scientific experience.

Severe acute pancreatitis is characterized by acinar cell injury with extensive tissue necrosis, inflammation, and hemorrhage. 1 In most patients it is associated with remote organ failure, sepsis, and a high death rate. In the absence of a clear pathophysiologic concept of acute pancreatitis, current treatment strategies still focus on the management of subsequent complications rather than the cause of the disease. In the search of an improved therapeutic concept, increasing experimental and clinical evidence has arisen that oxidative stress 2–4 and polymorphonuclear leukocytes 5 play an instrumental role in the disease process. Oxygen free radicals (OFRs) are a highly reactive biochemical species that exert their pathophysiologic effects by direct and indirect mechanisms. Directly, they attack lipids and proteins in the biologic membranes at the local site of generation. 6,7 Indirectly, they act on the arachidonic acid cascade by the production of thromboxane, which is known to lower tissue circulation by its potent platelet-aggregating and vasoconstricting effects. 8 Second, they increase the production of leukotriene B4, which promotes the activation of leukocytes. 9 Activated polymorphonuclear leukocytes themselves are known to release various lysosomal enzymes as well as OFR species (the so-called respiratory burst), which enhances tissue injury. 2 In addition to OFRs, nitric oxide (NO) is another highly reactive free radical that is involved in the physiology of circulation 10 and in pathophysiologic conditions such as inflammation. 11,12 NO is synthesized from the amino acid l-arginine by a family of enzymes summarized as nitric oxide synthase (NOS) that are present in endothelial cells, macrophages, platelets, and the pancreas. 12 To date three isoforms of NOS have been characterized: two of them are termed neuronal constitutive (ncNOS or NOS-1) and endothelial constitutive (ecNOS or NOS-3), which are constantly present and produce only small amounts of NO. The inducible NOS (NOS-2), the third NO isoform, produces larger amounts of NO and is present only after stimuli such as endotoxin or proinflammatory cytokines. 13,14 NO-mediated cytotoxicity is due to several mechanisms: NO rapidly reacts with the superoxide anion, which results in the formation of peroxynitrite and hydroxyl radicals, both powerful oxidants. 15 In addition, NO seems to be a mediator of prostaglandin synthesis. 16 The role of NO in acute pancreatitis has been controversial. There are several lines of evidence showing that NO seems to have a protective effect on local pancreatic cellular damage, mainly by inhibiting neutrophil accumulation. 16–18 However, the definite role and the exact relation among NO, OFR-derived radicals, and polymorphonuclear leukocytes remain fairly unknown. In the present study we aimed to address this issue in an in vivo experimental setup.

The role of reactive oxygen species (ROS) generated by hypoxanthine/xanthine oxidase (HX/XO) in the induction of apoptosis was studied in the human fibroblast cell line WI38. Apoptosis but not necrosis was observed in proliferating fibroblasts after 48 h incubation with 1 mM HX and 0.05 U/ml XO. Induction of apoptosis was hindered by catalase. Cell-cycle analysis revealed a reduction of cells in the S/G2 phase 24 and 48 h after stimulation, suggesting that ROS induce a G1 arrest in proliferating fibroblasts. This was supported by an accumulation of p53 and the cdk inhibitor p21WAF1/CIP1. Since apoptosis was not inducible in senescent fibroblasts our data indicate that ROS mainly induces apoptosis in proliferating cells. © 1997 Federation of European Biochemical Societies.