GASTRIC CANCERS IN SINGAPORE: POOR PROGNOSIS ARISING FROM LATE PRESENTATION

Background : Mortality rates from gastric cancer, apart from those derived from Japanese series, remain poor. This paper sought to determine the present outcome of gastric carcinoma in a predominantly Chinese population in Singapore. Prognostic factors useful in predicting survival were also evaluated in this population. Method : All cases of histologically confirmed gastric adenocarcinoma presenting in 1992 were entered into a prospective database. Prognostic factors related to age, sex, site of disease, depth of invasion, histological grade, nodal status and stage of disease were evaluated in patients with resectable disease to determine their utility in predicting survival. Results : Of 1310 consecutive patients with histologically proven adenocarcinomas, 37% had distant metastases at presentation predominantly in the liver (21%) and peritoneal cavity (20%). Sixty-four per cent of patients underwent surgery and in only 51% of these patients was resection of the turnour possible. Stages 111 and IV (T4N2) locally advanced disease were present in 38% of patients. Thus the majority of patients presented with late or metastatic disease (75%, stages 111 and IV). Sixty per cent of patients were alive at I year and 40% at 2 years after resection of the tumour (Kaplan-Meier survival plots). In contrast, no patient survived longer than a year if the tumour was not resectable (P < 0.001, log-rank test). Median survival of patients without surgery was 12 weeks. Median survival for patients with resected stage IV disease was 23 weeks, compared to 18 weeks after surgical bypass. Age, sex, site, depth of invasion and histological grade did not significantly predict survival. Patients with node-negative disease survived longer (2 year, 70%) than those with nodal involvement (2 years, 44%; P = 0.06, log-rank test). Pathologic staging with the TNM system was useful in predicting survival (P < 0.001). Sixty per cent of patients with stage I and II disease were alive at 2 years compared to 54% with stage III disease and 0% with stage IV disease. Conclusion : The prognosis of stomach cancer remains poor, due predominantly to late presentation. Pathologic TNM staging and nodal status were useful in predicting survival outcome after resection. If the tumour were resectable, survival was appreciable even in patients with advanced stage III (2 years, 54%) and stage IV (1 year, 40%) disease. Strategies to improve outcome should focus on early detection of gastric carcinomas.     

Fatty acid profiles in response to soybean oil lipid emulsion infusions in essential fatty acid-deficient miniature swine

The ability of soybean oil lipid emulsions to affect essential fatty acid deficiency (EFAD) and plasma fatty acid distribution was studied in neonatal pigs. The test animals were maintained on a fat-free diet prior to administration of lipid emulsion. Plasma and red blood cell (RBC) membrane levels of essential [linoleic (C-18:2 omega 6) and arachidonic (C-20:4 omega 6)] and nonessential [palmitic (C-16, palmitoleic (C-16:1 omega 7), stearic (C-18), and oleic (C-18:1 omega 9)] fatty acids and the triene:tetraene ratio [5,8,11-eicosatrienoic acid (C-20:3 omega 9):arachidonic acid (C-20:4 omega 6)] were monitored to ascertain the establishment of EFAD and its correction. Nonessential fatty acids were studied, as these components of lipid therapy have received little attention. Results indicate that soybean oil emulsions are effective in reversing fatty acid profiles found in EFAD, and both essential and nonessential fatty acids are under strict metabolic control.     

Comparison of the blood-brain barrier and liver penetration of acridine antitumor drugs

Summary The blood-brain barrier penetration of amsacrine and its analogs 9-({2-methoxy-4-[(methylsulfonyl)-amino]phenyl}amino)-,5-dimethyl-4-acridine carboxamide (CI-921) and M-[2-(dimethylamino)ethyl]-acridine-4-carboxamide (AC) was measured in the barbiturate-anesthetized mouse. After intracarotid administration, AC was almost completery extracted (90%) in a single transit through the brain capillaries, whereas CI-921 (20%) and amsacrine (15%) were moderately extracted. AC is retained in the brain; no loss of AC from the brain was apparent at 1, 2, 4, or 8 min after injection. In contrast, after intraportal administration, 75% of the AC, 94% of the CI-921, and 57% of the amsacrine was extracted in a single transit through the hepatic vasculature. Rather than being retained in the mouse liver, these acridine antitumor agents show time-dependent loss (t _1/2=10 min for amsacrine and AC, 24 min for CI-921). We conclude that unlike most antitumor agents, these acridine drugs appear to penetrate the blood-brain barrier readily.This study was supported by the Auckland Medical Research Foundation (New Zealand), by the Medical Research Foundation (New Zealand), by the National Science Foundation (United States/New Zealand Cooperative Science Program), by the United States Veterans Administration, and by NIH grant NS 25554     

Gastric cancer mortality and nitrate levels in Wisconsin drinking water.

The association between nitrate levels in public and private sources of drinking water and gastric cancer mortality in Wisconsin was investigated in a case-control study. All gastric cancer deaths of Wisconsin residents from 1982 through 1985 were compared with deaths from other causes (controls), and nitrate levels in the home drinking water of these residents were determined. Nitrate measures for public sources were obtained from historic nitrate data from municipal sources that existed in 1970. Nitrate measures for private water sources were obtained by testing the wells individually at the existing residences. Controls were matched individually to gastric cancer cases with respect to sex, year of birth, year of death, Wisconsin birth, and Wisconsin residency at the time of death. Matched-pair analyses were performed on the paired data, and the following levels of nitrate-nitrogen exposure were used as indicators of exposure: 0.5, 2.5, 5.0, and 10.0 mg/l. Matched-pair analysis was also performed for which private water supply constituted exposure. Odds ratios and 95% confidence intervals were, respectively, 0.92 (0.75, 1.12); 0.97 (0.74, 1.35); 0.86 (0.69, 1.08); 1.50 (0.12, 18.25); and 1.09 (0.82, 1.47) for exposure to private well-water sources. These results did not indicate an increased risk of gastric cancer at any level.     

Suppression of presynaptic calcium currents by hypoxia in hippocampal tissue slices.

We tested the hypothesis that suppression of inward calcium current in presynaptic terminals is the cause of failure of synaptic transmission early during cerebral hypoxia. Postsynaptic responses in CA1 zone of hippocampal tissue slices were blocked either by the combined administration of 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 3-((+-)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP) or by lowering extracellular calcium concentration ([Ca2+]o). Repetitive orthodromic activation of central neurons caused transient decrease of [Ca2+]o (measured by ion selective microelectrodes) in neuropil, attributable to influx of Ca2+ in presynaptic terminals. Presynaptic [Ca2+]o responses were rapidly and reversibly suppressed when oxygen was withdrawn from hippocampal tissue slices. The 'resting' baseline level of [Ca2+]o declined at first gradually, then precipitously as in spreading depression (SD). Presynaptic volleys during high frequency train stimulation were also depressed somewhat before SD began. We conclude that (1) presynaptic Ca2+ currents fail during hypoxia, perhaps because 'resting' intracellular free Ca2+ activity is increased and, in part, also because of partial failure of presynaptic impulse conduction; (2) the influx of Ca2+ into brain cells in hypoxic spreading depression is not mediated by glutamate/aspartate dependent channels.