Optimal treatment of Zollinger-Ellison syndrome and related conditions in elderly patients.

Zollinger-Ellison syndrome is characterised by refractory peptic ulcer disease, severe diarrhoea and gastric acid hypersecretion associated with an islet-cell tumour of the pancreas (gastrinoma). The true incidence and prevalence of this rare disease is unknown; in the US, the frequency is one per one million people and the age at presentation varies from 7 to 90 years. Zollinger-Ellison syndrome is sporadic in 62-80% of cases and in 20-38% of cases is associated with multiple endocrine neoplasia type 1 (MEN 1). The diagnosis of Zollinger-Ellison syndrome is certain when the plasma gastrin is >1000 pg/mL and the basal acid output is >15 mEq/h in patients with an intact stomach, >5 mEq/h in gastrectomised patients, or when this hypergastrinemia is associated with a pH <2. The treatment is based on control of gastric acid hypersecretion and of the malignant tumour and its possible metastases. Proton pump inhibitors are the most effective antisecretory drugs and can be administered in the elderly at high dosages without drug-related adverse effects. As an initial therapy, daily dosages of omeprazole 80-100 mg or pantoprazole 40-160 mg are employed. In long-term treatment the doses can be greatly reduced once effective control of the gastric output has been established. Intravenous proton pump inhibitors may be administered when patients cannot take oral therapy, particularly in acute conditions. All sporadic localised gastrinomas should be excised if possible. When liver metastases are also present, their debulking may improve symptoms and survival, and facilitate medical treatment. There is some controversy as to the surgical approach for gastrinomas associated with MEN 1. Somatostatin analogues can be useful in reducing gastric acid hypersecretion, serum gastrin and gastric enterochromaffin-like (ECL) cells and can thus contribute to treating the disease more effectively. Their antiproliferative effect can be used in treating liver metastases. Chemotherapy is not the therapy of choice in patients with gastrinomas and is indicated only in those with malignant progressive disease; interferon alpha, embolisation and chemoembolisation are not advisable for the elderly. The treatment of elderly Zollinger-Ellison syndrome patients, similarly to all elderly oncological patients, should be based on the use of comprehensive geriatric assessment. This will enable the clinician to define the functional status of the elderly person, to decide whether the patient can tolerate surgery and/or the stress of antineoplastic therapy, and finally, to determine whether this patient can tolerate an aggressive treatment for Zollinger-Ellison syndrome or whether the only possible choice is palliative relief of symptoms.

Coagulative disorders in human acute pancreatitis: role for the D-dimer.

INTRODUCTION AND AIMS: We investigated coagulative disorders, particularly the role of the D-dimer, in acute pancreatitis where coagulation abnormalities related to disease severity are known to occur. METHODOLOGY: D-dimer levels in 30 patients with acute pancreatitis were evaluated; pancreatitis was mild and uncomplicated in 11 patients, accompanied by complications in 15, and severe in 4. We attempted to find a relationship between the D-dimer level and the antithrombin III level, prothrombin time, partial thromboplastin time, the C-reactive protein level, and results of routine laboratory tests. RESULTS: In the 11 patients with uncomplicated pancreatitis, the D-dimer level increased about 1.5 times over the limit, while in the 15 patients with complications and the four patients with severe pancreatitis, the D-dimer level increased about seven times above the normal limit; this difference was highly significant (p < 0.0001). The rise in the D-dimer level was inversely related to albumin and calcium levels (p = 0.0001) and directly related to the C-reactive protein level, fibrinogen level and leukocyte count (p = 0.0001), prothrombin time (p = 0.006), partial thromboplastin time (p = 0.03), and acute abdominal collections and lung involvement (p = 0.0001). The increase appeared early on, lasting for the entire study and peaking on days 3-6. CONCLUSIONS: The D-dimer is the expression of pancreatitis and the extension of systemic involvement; it may be considered a prominent link in the chain of events leading to severe disease.

Impaired alveolar gas exchange in acute pancreatitis.

We evaluated the alveolar-arterial oxygen difference (deltaA-a) and the ratio between PaO2 and the fractional concentration of inspired oxygen (P/F) in acute pancreatitis. Eleven patients had mild uncomplicated disease, six showed acute abdominal fluid collections, six had acute abdominal collections and asymptomatic x-ray lung involvement, three presented transient dyspneic episodes, and four had severe acute pancreatitis requiring prolonged oxygen therapy. In the uncomplicated disease, respiratory function was normal; in the six patients with abdominal collections only, deltaA-a increased by 50% and P/F decreased by 20-30%; in the six patients with abdominal collections and asymptomatic x-ray lung involvement, deltaA-a increased by 50-70% and P/F decreased by 40%; the three patients with dyspneic episodes showed a twofold increase in deltaA-a and a 40% decrease in P/F; the four patients with severe pancreatitis had a two- to threefold increase in deltaA-a and a 40-50% decrease in P/F. Hence respiratory function is normal only in uncomplicated pancreatitis; in the presence of complications, disturbance of gas exchange always occurs, requiring careful control and treatment.

Apoptosis in the peripheral blood mononuclear cells as a self-limitation process in human acute pancreatitis.

BACKGROUND/AIM: Acute pancreatitis is primed and sustained by a chain of immuno-inflammatory factors. In this study, we investigated the possible existence of peripheral blood mononuclear cell apoptosis as a self-limitation mechanism in acute pancreatitis. METHODS: Peripheral blood mononuclear cell apoptosis was determined cytofluorometrically daily for 10 days from the onset of the illness in 27 consecutive patients (18 having mild uncomplicated acute pancreatitis and 9 having pancreatitis with complications) and was related to peripheral blood counts, including reticulocytes and reticulocyte fractions, and albumin, fibrinogen, and C-reactive protein levels. RESULTS: In the 18 patients with uncomplicated acute pancreatitis, the rate of peripheral blood apoptosis increased progressively until days 5-6 and then decreased. The 9 patients who developed complications showed levels of peripheral blood apoptosis stable across the five periods and lower than those with uncomplicated disease during the first four periods. This difference was statistically significant (p = 0.002) only on days 7-8. On days 9-10, the patients with complications showed higher levels of peripheral blood apoptosis than those with mild uncomplicated acute pancreatitis (p = 0.0005). Peripheral blood apoptosis was not significantly related to the other laboratory parameters, but there was a trend towards an inverse relation to reticulocytes and total leucocytes (p < 0.09). CONCLUSIONS: Peripheral blood apoptosis may act as a mechanism of self-limitation of the process of acute pancreatitis. Its effects, however, seem to be hampered and delayed by the presence of complications.