Surgery for gastroenteropancreatic tumours in multiple endocrine neoplasia type 1: review and personal experience.

Multiple endocrine neoplasia type 1 (MEN1) gastro-entero-pancreatic (GEP) tumours develop from the pancreatic islets and from the endocrine cells of the duodenal and gastric mucosa. Even if GEP tumours have generally a benign course, a subgroup of them shows an aggressive behaviour and is a major cause of death amongst MEN1 patients. Diagnosis of insulinoma should lead promptly to pancreatic surgery. MEN1 gastrinomas are multiple and almost exclusively localized in the duodenum. Cure rate for Zollinger-Ellison syndrome in MEN1 is low when surgery is limited to tumour enucleation or full thickness duodenal wall resection. Conversely, pancreatoduodenectomy is followed by higher chance of cure. For nonfunctioning tumours exceeding 1 cm diameter in size a prompt treatment is recommended due to their high malignant potential. Gastroscopic surveillance is indicated for the frequent occurrence of multiple, small, type 2 fundic carcinoids. Endoscopic removal is possible for lesions growing in the mucosa-submucosa, but partial or even total gastrectomy is recommended for the small number of gastric carcinoids infiltrating the muscular layers.

Biochemical changes and their relationship with morphological and functional findings in pig heart subjected to lasting volume overload: a possible role of acylphosphatase in the regulation of sarcoplasmic reticulum calcium pump.

We evaluated the changes in sarcoplasmic reticulum (SR) function and the parallel hemodynamic and morphological modifications in a heart subjected to volume overload. We also determined the levels of acylphosphatase, a cytosolic enzyme, that could play a regulatory effect on SR Ca(2+) pump by hydrolyzing the phosphorylated intermediate of this transport system. For this, swine hearts were subjected to volume overload by aorta-cava shunt for 1, 2, or 3 months. Changes in heart contractility reflected modifications of SR function, whose reduction after 1 month of overload was followed by a gradual recovery. A decrease in SERCA2a protein and mRNA content was shown from 1 month and remained for the following 2 months. Phospholamban content and its phosphorylation status were not modified. Acylphosphatase was unchanged at 1 month, but at 2 months this enzyme exhibited an increased activity, protein and mRNA expression. Morphological alterations consisting of the cytoskeletal architectures, intermyofibrillar oedema, swollen mitochondria and abnormality of the membrane system (T-tubule and SR cisternae) were particularly evident after 1 month but almost disappeared after 3 months. These results suggest that our overloaded hearts underwent a substantial recovery of their structural and biochemical properties at 3 months after surgery. A possible involvement of acylphosphatase in the modification of SR function is discussed.

Are macrophages involved in early myocardial reperfusion injury?

BACKGROUND: Neutrophils are the predominant phagocytes in the early stages of myocardial ischemia-reperfusion response and are also implicated in the development of tissue damage. This study examined the role of recruited macrophages in the evolution of this tissue injury. METHODS: Farm pigs were subjected to 30 minutes of myocardial ischemia followed by 30 minutes of reperfusion. Biopsy samples were taken from the control, ischemic, and ischemic-reperfused left ventricle wall and processed for both morphologic and biochemical analyses. In situ production of tumor necrosis factor-alpha was evaluated by Western blot and immunofluorescence. A full hemodynamic evaluation was also performed. RESULTS: Myocardial ischemia and early reperfusion caused marked neutrophil and macrophage tissue accumulation and tumor necrosis factor-alpha production by the injured tissue. Immunofluorescence studies allowed us to localize tumor necrosis factor-alpha predominantly in tissue-infiltrating macrophages. No depression in the global myocardial contractile function was observed, either during ischemia or after reperfusion. CONCLUSIONS: These data suggest that the newly recruited macrophages within the ischemic and early post-ischemic myocardium may play a role in promoting neutrophil tissue infiltration and subsequent neutrophil-induced tissue dysfunction by producing tumor necrosis factor-alpha.

Early changes induced in the left ventricle by pressure overload. An experimental study on swine heart.

The purpose of this study was to evaluate the early changes in sarcoplasmic reticulum (SR) function and the parallel morphological and hemodynamic modifications occurring in the heart following pressure overload. As regards SR function, we also explored the levels of acylphosphatase, an enzyme which might have a regulatory effect on the SR Ca(2+) pump by hydrolyzing the phosphorylated intermediate of this transport system. Pigs subjected to pressure overload by aortic stenosis for 6, 12, 24, 48, 72, and 96 h were compared to sham-operated controls. At each of the considered times both SR Ca(2+)-ATPase activity and Ca(2+) uptake, as well as acylphosphatase activity, were significantly enhanced in the pressure overloaded compared to the control hearts, with a maximal increase at 6 h; moreover, a positive and significant correlation was found between these parameters. The modifications in the activities of Ca(2+)-ATPase and acylphosphatase reflected an increased expression of these proteins, while phospholamban did not show significant changes in its concentration nor in its phosphorylation status. As for hemodynamic parameters, rapid changes in the left ventricular function were observed and especially the early hours following the aortic stenosis appeared to be crucial for the adjustment of heart function. The most relevant morphological finding was a focal disarrangement of the myofibrillar pattern which was very evident at 6 h, and progressively attenuated at later times. Taken together our data suggest that an early adaptation to the increased hemodynamic working overload is a consistent activation of the contractile apparatus which reflects, at least in part, an enhanced SR function. Besides the changes in Ca(2+) pump protein expression, increased acylphosphatase levels might also contribute to this effect.

[Advanced cancer of the exocrine pancreas treated by a long-acting luteinising hormone releasing hormone (LH-RH) analogue, triptorelin: phase II study]. / Cancers du pancréas exocrine évolués traités par un analogue retard de la Luteinising Hormone Releasing Hormone (LH-RH) la triptoréline: étude de phase II.

Between 1987 and 1989 we treated 18 patients with advanced pancreatic adenocarcinoma with a long acting LH-RH analogue: triptorelin. Seventeen patients were evaluated. We obtained no objective responses. The median survival time was 4.5 months. The treatment was well tolerated without any major secondary effects. The absence of dosage of hormonal receptors did not allow the selection of hormone sensitive patients. The future study of hormone therapy will analyse the pancreatic hormonal receptors.