Serial immunological testing in patients with gastric cancer.

Standard immunological parameters measuring non-specific cellular immune reactivity were determined in 175 patients with different stages of gastric cancer prior to surgery and during follow-up. Several tests measuring monocyte activity were also employed. The total number of T cells and their subpopulations Ta and T29o was unchanged except depression of T29o in stage IV. The blastogenic response of lymphocytes to PHA as assessed by stimulation of protein synthesis was only depressed in stage IV. In contrast the PHA-induced lymphokine production was increased in all patients but the differences were significant for stage III and IV. Monocyte Fc receptor expression was increased in stages II-IV, while nitro blue tetrazolium reduction and antibody dependent cellular cytotoxicity of monocytes was elevated in stage IV. The number of extractable monocytes was not increased. Longitudinal studies suggested that most of the parameters normalized during follow-up. No major long-term impact of chemoimmunotherapy (5-FU + BCG) on the immune parameters was observed except a transient increase in PPD reactivity approximately 1 year after commencement of treatment. In patients with stage III gastric cancer the increased occurrence of suppressor cells (mostly monocytes) and elevated cytostatic activity of monocytes was associated with a longer survival while the increased lymphokine production and Fc receptor expression were seen in the group of patients succumbing earlier. We concluded that most of the changes in immune parameters were seen only in advanced disease and paradoxically disappeared in the course of disease. The determination of monocyte activity seems to be a sensitive indicator of immune system dearrangements in earlier stages of cancer and a useful prognostic factor in gastric cancer.

The in vitro migration inhibition of mononuclear cells in patients with colorectal carcinoma.

The response of peripheral blood mononuclear cells to PHA and PPD in migration inhibition test has been studied in patients with Duke's B-D colorectal carcinoma. It was found the response of patients cells to both stimulants was increased. This enhanced lymphokine release and/or production was closely connected with the tumor load. The implications of these findings to the regulatory mechanisms of the immune response in cancer patients are briefly discussed.

Helicobacter pylori, gastrin and cyclooxygenases in gastric cancer.

BACKGROUND: Tumors arising in the stomach have worldwide distribution and the infection with Helicobacter pylori (HP) has been implicated in causation of this disease. The HP discovery, which is considered as the greatest advance of gastroenterology at the dawn of 3rd millennium, is accompanied by hypergastrinemia, which seems to play a key role in gastric cancerogenesis but no study was undertaken to assess the relationship between the HP infection and coexpression of gastrin and cyclooxygenases (COX), the rate limiting enzymes in the eicosanoids production. AIMS: Since gastrin is recognized as a effective gastric mitogen, it could be capable to induce COX-2, a potent tumor growth promoting and angiogenic factor, we decided 1) to compare the seroprevalence of HP and its cytotoxic protein, CagA, in gastric cancer patients with those in age- and gender-matched controls; 2) to determine the gene expression of gastrin and its receptors (CCK(B)-R) in gastric cancer, 3) to assess the plasma levels, gastric lumen and tumor tissue contents of gastrin and 4) to examine the mRNA and enzyme protein expression of COX-1 and COX-2 in cancer tissue and intact gastric mucosa before and after HP eradication. MATERIAL AND METHODS: The trial material included 20 patients with gastric cancers and 100 age- and gender-matched controls. Anti-HP and anti-CagA IgG seroprevalence was estimated by specific antisera using ELISA tests. Gene expressions of gastrin, CCK(B)-R, COX-1 and COX-2 was examined using RT-PCR with GAPDH as a reference and employing Western blot for COX-2 expression, while gastrin was measured by RIA. RESULTS: The seroprevalence of HP, especially that expressing CagA, was significantly higher in gastric cancers than in controls. Both gastrin and CCK(B)-R mRNA were detected by RT-PCR in the cancer tissue and similarly COX-2 mRNA and protein were found in most of cancers and in the HP infected antral mucosa but not in HP eradicated patients in whom only cancer tissue but not gastric mucosa expressed COX-2. The gastric cancer tissue contained 20 times more of immunoreactive gastrin than the HP infected antral gastric mucosa and following HP eradication the gastrin content in the tumor and antrum showed a marked and significant reduction. No significant change in CCK(B)-R expression was noticed before and after HP eradication in the tumor and the corpus mucosa. CONCLUSIONS: 1). Gastric carcinoma coexpresses gastrin, its receptors (CCK(B)-R), and COX-2; 2) HP infection may contribute to gastric cancerogenesis via gastrin andCOX-2 that may account for the stimulation of tumor growth, angiogenesis, and reduction in apoptosis 3) HP positive patients developing gastric cancer should be considered for HP eradication to reduce the HP provoked hypergastrinemia and COX-2 overexpression in the tumor tissue.

Vesico-ileal fistula caused by a foreign body.

An enterovesical fistula due to an intestinal foreign body is presented and the therapeutic aspects of the lesion are discussed.

Peroxidase activity in peritoneal neutrophils of patients with terminal renal failure treated by intermittent peritoneal dialysis.

Peroxidase activity was assessed cytochemically in the peritoneal dialysate neutrophils of 50 patients with terminal renal failure treated by intermittent peritoneal dialysis. In 22 patients cells were harvested for the second time after they developed peritonitis as a complication of the treatment. The results obtained were compared with those in the control group consisting of 30 patients with normal renal function. The patients treated by peritoneal dialysis showed both in the complication-free period and in the course of peritonitis significantly higher peroxidase activity in the neutrophils, as revealed by the semiquantitative score test. In the course of peritonitis, the neutrophils peroxidase activity was significantly lower than in the complication-free period.

Helicobacter pylori infection, gastrin, cyclooxygenase-2, and apoptosis in colorectal cancer.

Helicobacter pylori (HP) infection is usually accompanied by an increased plasma level of gastrin, a potent mitogen able to induce cyclooxygenase (COX)-2. This study examined (a) the seroprevalence of HP, its cytotoxic protein, CagA, and cytokines (tumor necrosis factor alpha, interleukins 1beta and 8) in 80 patients with colorectal cancers, before and after the removal of tumor, compared with 160 age- and gender-matched controls; (b) the gene expression of gastrin and its receptors (CCKB-R) in the cancer tissue, (c) the plasma levels and tumor tissue contents of gastrin, and (d) the mRNA expression of COX-1, COX-2, and apoptotic proteins (Bax and Bcl2) in cancer tissue and intact colonic mucosa. Anti-HP IgG, anti-CagA IgG seroprevalence, and cytokine levels were analyzed by enzyme-linked immunosorbent assay tests; gene expressions of gastrin, CCKB-R, COX-1, COX-2, Bax, and Bcl2 by reverse transcriptase polymerase chain reaction; and gastrin by radioimmunoassay. The seroprevalence of HP, especially that expressing CagA, was significantly higher in cancer patients than in controls and did not change 1 week after tumor resection while plasma cytokines were significantly reduced after this operation. Both gastrin and CCKB-R mRNA were detected in the cancer tissue and the resection margin; similarly, COX-2 mRNA was expressed in most of cancers and their resection margin but not in intact colonic mucosa, where only COX-1 was detected. The colorectal cancer tissue contained several folds more immunoreactive gastrin than cancer resection margin and many folds more than the intact colonic mucosa. We conclude that colon adenocarcinoma and its resection margin overexpress gastrin, its receptors, CCKB-R, and COX-2, and that HP infection may contribute to colonic cancerogenesis via overexpression of gastrin and COX-2, which may account for the stimulation of the tumor growth and the reduction in apoptosis as documented by enhanced mRNA expression of anti-apoptotic Bcl2 over proapoptotic Bax proteins.