Docetaxel in advanced gastric cancer--review of the main clinical trials

The aim was to investigate the activity of docetaxel in advanced gastric cancer either as single agent or in combination with other drugs. A systematic review was carried out using the databases of Medline, Embase and CancerLit. Results from ASCO and ESMO meetings during 2002 were also included. Eight phase II trials focused on docetaxel as a single agent. Considering collectively the 262 evaluable patients enrolled in these studies, the mean response rate (RR) was 19% (CI 95% 14-24%). Docetaxel was well tolerated with a dose-limiting myelosuppression (grade 3-4 neutropenia in 36-95% of cases). Adding fluorouracil, an RR ranging from 22% to 86% was registered, due to differences in populations studied (young vs. elderly) and modalities of drug administration (continuous vs. bolus infusion). RRs for docetaxel-cisplatin combination were 56%, 37% and 36% in three phase II trials and 35% in a phase III trial. The addition of both cisplatin and fluorouracil to docetaxel did not increase toxicity. Randomized trials comparing docetaxel-cisplatin-fluorouracil with ciplatin-fluorouoracil or epirubicin-cisplatin-fluorouracil, the most commonly used regimens, are ongoing. The future results of the above phase III studies could indicate docetaxel as a key drug to improve treatment of patients with advanced gastric cancer.     

Gastric stump lymphoma five years after distal gastrectomy

We report the case of a 77-year-old man who developed low grade B cell non-Hodgkin's lymphoma of the gastric stump 5 years after undergoing a distal gastrectomy for benign gastric ulcer. Lymphoma occurring in the post-operative stomach would appear to be very rare, with only 14 previously recorded cases. The median period of lymphoma onset after ulcer surgery is about 20 years (range 9-43 years) and gastric remnants of lymphoma are generally diagnosed in low stage, when surgery is possible and makes the prognosis good. The clinical case presented herein is quite different from the others. The patient developed lymphoma within 5 years of the ulcer surgery, thus, earlier than generally reported in literature; he presented with massive regional and extra-regional nodes involvement and liver metastases and he poorly responded to antiblastic chemotherapy. The pathogenetic role of Helicobacter pylori (HP) infection and the possibility of malignant lymphoma developing in the gastric stump are discussed.     

The Dexamethasone Suppression Test in Essential Headache

SYNOPSIS
After neuropsychological evaluation, we administered the dexamethasone suppression test to eleven patientssuffering from muscle-contraction headache and to thirteen patients affected by migraine, in order to verify a possiblecorrelation between a chronic pain such as headache and a cortisolemic response to dexamethasone. None of themappeared to be suffering from depressive syndrome; all patients were DST suppressors. These data suggest that thedexamethasone suppression test does not correlate with chronic pain, but with depression, consistent with the highspecificity of this marker test for depression.     

Expression of GAL mRNA in rat hypothalamus: effect of frontal deafferentation and colchicine treatment.

The expression of galanin (GAL) mRNA was determined by in situ hybridization after frontal deafferentation and colchicine treatment in the rat hypothalamus. Frontal deafferentation significantly increased the signal in the paraventricular nucleus (PVN), the supraoptic nucleus (SON), and dorsomedial nucleus (DMN). Colchicine treatment induced a diffuse enhancement of GAL mRNA in hypothalamic nuclei. When the two treatments were combined there was an additivity of GAL mRNA expression in the previous hypothalamic nuclei and also in the arcuate nucleus (AN), where the single treatments did not modify the signal. These results suggest the regulation of GAL mRNA expression mediated by a multineuronal pathway, separate from the colchicine-induced GAL mRNA increase.     

P2X7 receptor expression in evolutive and indolent forms of chronic B lymphocytic leukemia.

Human leukocytes express a receptor for extracellular nucleotides, named P2X7R, that in lymphocytes can either mediate cell death or proliferation, depending on the level of activation. The authors have investigated P2X7R expression and function in 21 patients affected by B-cell chronic lymphocytic leukemia, 13 with an evolutive and 8 with an indolent variant of the disease. Resting cytoplasmic Ca++ concentration was significantly higher in lymphocytes from patients with the evolutive compared with indolent variant. Furthermore, in the former, P2X7R stimulation triggered a Ca++ influx significantly larger. Higher Ca++ influx correlated with an increased P2X7R expression in the lymphocytes from patients with the evolutive form. Finally, incubation in the presence of extracellular adenosine triphosphate decreased spontaneous proliferation of lymphocytes from patients affected with the evolutive variant but had no effects on lymphocytes from patients with the indolent form. These results suggest that expression and function of P2X7R may correlate with the severity of B-cell chronic lymphocytic leukemia.     

Studies on the indirect feedback inhibition of cholinergic neurons triggered by oxotremorine in striatum

Oxotremorine produced 30–75% increases in rat striatal acetylcholine content and 10–15% decreases in choline content at the subtremorogenic doses of 0.34–1.34 μmol/kg, without affecting choline acetyltransferase and acetylcholinesterase activities and the sodium-dependent high affinity uptake of choline. The increases in acetylcholine was blocked by atropine and by reserpine indicating that oxotremorine indirectly influences the intrinsic striatal cholinergic neurons through a monoamine-mediated negative feedback loop. Experiments designed to interfere with neurotransmitter function indicated that noradrenaline and not dopamine or serotonin, mediated the response to oxotremorine.     

Relationship of serum lactate dehydrogenase level with first remission length in adult acute lymphocytic leukaemia

Several features have a prognostic value in adults with acute lymphocytic leukaemia (ALL). However, in about two-thirds of all cases prognosis remains quite variable, with a substantial number of early relapses. This study shows in 118 adult patients who attained complete remission (CR) between 1978 and 1984 that pretreatment serum total lactate dehydrogenase (LDH) activity was inversely correlated with first CR length. The prognostic value of LDH was higher than that of any other features both in univariable and in multivariable analysis. The value was significant in the whole series as well as in patients who lacked other high risk features. Among non-high risk and low-WBC count cases, patients with LDH less than or equal to 500 U/l had a median first CR duration of 27 months, and a projected 5-year relapse free survival of 36%, versus 9 months and 12% of patients with LDH greater than 500 U/l. These results fit well with the results of a study of ALL in children, and suggest that pretreatment serum total LDH activity is an important risk determinant in adult ALL.