(1/1217) Laparoscopic staging of gastric cancer is safe and affects treatment strategy.
The accuracy of laparoscopic staging has been documented, but its safety and impact on clinical decision making are less clear. In a prospective series of 64 patients referred to a single consultant, laparoscopy was performed in 49, after exclusion of patients unlikely to derive benefit from laparoscopic staging. The prelaparoscopy treatment plan was altered in 17 (34%). Laparoscopy detected 11 cases of peritoneal and four cases of liver metastasis, of which nine and two, respectively, were not detected by CT scan. Laparoscopy was useful in assessing fitness for major surgery, the planned extent of which was reduced in five cases as a result. Port site metastasis occurred in one case of stage IVB cancer, in conjunction with widespread progressive disease. Laparoscopic staging is recommended in gastric cancer, since it causes important changes to the management plan in one-third of cases, and the risks of port site metastasis appear low. (+info)
(2/1217) Signet ring cell carcinoma of the stomach: a clinicopathological comparison with the other histological types.
A retrospective analysis was carried out on 93 patients with signet ring cell carcinoma of the stomach operated on between 1985 and 1995, to review the clinicopathologic characteristics from the database of gastric cancer at Sendai National Hospital. The results were compared with those for 590 patients with other types of gastric carcinoma. Women were afflicted as commonly as men in the signet ring cell carcinoma group. These patients tended to be younger and to have larger tumors. The histological type was commonly scirrhous and infiltrative. The survival of patients with signet ring cell carcinoma was worse than that of patients with other types of gastric cancer but the difference was not statistically significant. Patients with early signet ring cell carcinoma had a good prognosis, similar to that of the other groups. However, prognosis of patients with advanced signet ring cell carcinoma was poor compared with patients with other types of this disease. In multivariate analysis, the statistical significant prognostic factors were vascular microinvasion and tumor location. These findings suggest that signet ring cell carcinoma of the stomach should be regarded as a distinct type of gastric cancer. (+info)
(3/1217) Oxamflatin is a novel antitumor compound that inhibits mammalian histone deacetylase.
Oxamflatin [(2E)-5-[3-[(phenylsufonyl) aminol phenyl]-pent-2-en-4-ynohydroxamic acid] induces transcriptional activation of junD and morphological reversion in various NIH3T3-derived transformed cell lines. We found that oxamflatin showed in vitro antiproliferative activity against various mouse and human tumor cell lines with drastic changes in the cell morphology and in vivo antitumor activity against B16 melanoma. Oxamflatin caused an elongated cell shape with filamentous protrusions as well as arrest of the cell cycle at the G1 phase in HeLa cells. These phenotypic changes of HeLa cells were apparently similar to those by trichostatin A (TSA), a specific inhibitor of histone deacetylase (HDAC). The effect of oxamflatin on the transcriptional activity of the cytomegalovirus (CMV) promoter was examined and compared with known HDAC inhibitors, TSA, sodium n-butyrate, and FR901228. Oxamflatin as well as all these inhibitors greatly enhanced the transcriptional activity of the CMV promoter in a dose-dependent manner. Oxamflatin, like TSA, inhibited intracellular HDAC activity, as a result of which marked amounts of acetylated histone species accumulated. Finally, effects on expression of several endogenous genes involved in cell morphology and cell cycle control in HeLa cells were analysed. Expression of gelsolin, cyclin E and Cdk inhibitors including p21WAF1/Cip1 was highly augmented, while that of cyclin A and cyclin D1 was decreased by oxamflatin. These results suggest that changes in the expression pattern of the genes regulating cell morphology and the cell cycle due to histone hyperacetylation are responsible for the antitumor activity, the morphological change and the cell cycle arrest induced by oxamflatin. (+info)
(4/1217) Asbestos related mortality in Northern Ireland: 1985-1994.
BACKGROUND: The association between Belfast and research into the hazardous effects of asbestos exposure goes back many years. This paper aims to update previous papers and review the burden of asbestos related disease in Northern Ireland today. METHODS: A study was carried out of all deaths in Northern Ireland between 1985 and 1994 inclusive, in which an asbestos related disease was mentioned anywhere on the death certificate. RESULTS: During this 10 year period, 527 asbestos related deaths were recorded; 88 per cent of these were in men. A total of 410 (77.8 per cent) were registered as the primary cause of death but only 405 (76.9 per cent) of cases were the subject of an autopsy. Standardized rates of pleural cancer in males have been increasing at 3.2 per cent per year though the trend was not significant. Lower rates in the last two years may herald the commencement of a decline. Deaths were clustered around the Belfast estuary, the site of Northern Ireland's shipbuilding industry. High proportional mortality ratios were demonstrated for occupations associated with the shipbuilding and construction industries. Evidence is presented that casts doubt on the attribution of peritoneal cancers in females to asbestos exposure. If lung cancers are included, there may be an average of 81 asbestos related deaths in Northern Ireland every year. CONCLUSION: Asbestos related diseases continue to extract a heavy burden of ill health in Northern Ireland today. There are some indications that the upward trend may be on the wane but confirmation of this will have to await further data. Measures to reduce exposure in the workplace to both asbestos and to tobacco smoke are the only means of reducing this burden. (+info)
(5/1217) Repeated cycles of retrovirus-mediated HSVtk gene transfer plus ganciclovir increase survival of rats with peritoneal carcinomatosis.
Peritoneal carcinomatosis is a common clinical situation that requires novel therapeutic approaches. We investigated the efficiency of an HSVtk gene therapy for the treatment of peritoneal carcinomatosis induced in syngeneic rats by DHD/K12 colon carcinoma cells. In this setting, the efficiency of two different retrovirus producing cell lines (GP+AmEnv12 and FLYA13) was compared. Rats treated with a single injection of retrovirus producing cells followed by a 5-day course of ganciclovir treatment showed an increased survival as compared with control animals. Animals treated with three injections of producing cells, each followed by a 4-5-day course of ganciclovir treatment, showed an increased survival as compared with control rats and with those treated with a single cycle of retrovirus producing cells plus ganciclovir. However, only a few animals remained tumor-free after day 180. There was no difference between the two producing cell lines in any of the experiments. RT-PCR demonstrated a faint expression of the tk transgene in the liver, spleen, epiploon, bowels and the lung of the animals injected with the HSVtk producing cells, reflecting most likely the transduction of only a limited number of cells. (+info)
(6/1217) Immunohistochemical analysis of PAI-2 (plasminogen activator inhibitor type 2) and p53 protein in early gastric cancer patients with recurrence: a preliminary report.
BACKGROUND: High levels of urokinase-type plasminogen activator (u-PA) were demonstrated in gastric carcinomas along with inhibitors of plasminogen activators (PAI-1 and PAI-2). They may influence the ability to invade and metastasize and therefore be of importance to the risk of recurrence of stomach neoplasms after curative operation. This also appears to be the case for p53 mutations and p53 protein overexpression. METHODS: Six patients, all differentiated cancer cases who developed recurrent disease 5-10 years after curative operations for early gastric cancers (recurrence group), were studied in comparison with 49 patients who had no recurrence more than 10 years after similar surgery (control group). The expression of u-PA, PAI-1, PAI-2 and p53 was compared immunohistochemically in the recurrence and control groups. RESULTS: The expression of PAI-2 was significantly more frequent in the recurrence group, being found in five (83.3%) patients vs eight (16.3%) in the control group. p53 was expressed in five (83.3%) patients in the recurrence group and in 15 (30.6%) in the control group; the rate was again significantly higher in the former. CONCLUSION: The results suggest that PAI-2 and p53 expressed in differentiated early gastric cancers are possible indices of the risk of recurrence. (+info)
(7/1217) Phase I study of 90Y-labeled B72.3 intraperitoneal administration in patients with ovarian cancer: effect of dose and EDTA coadministration on pharmacokinetics and toxicity.
The tumor-associated glycoprotein 72 (TAG-72) antigen is present on a high percentage of tumor types including ovarian carcinomas. Antibody B72.3 is a murine monoclonal recognizing the surface domain of the TAG-72 antigen and has been widely used in human clinical trials. After our initial encouraging studies (M. G. Rosenblum et al., J. Natl. Cancer Inst., 83: 1629-1636, 1991) of tissue disposition, metabolism, and pharmacokinetics in 9 patients with ovarian cancer, we designed an escalating dose, multi-arm Phase I study of 90Y-labeled B72.3 i.p. administration. In the first arm of the study, patients (3 pts/dose level) received an i.p. infusion of either 2 or 10 mg of B72.3 labeled with either 1, 10, 15, or 25 mCi of 90Y. Pharmacokinetic studies demonstrated that concentrations of 90Y-labeled B72.3 persist in peritoneal fluid with half-lives >24 h after i.p. administration. In addition, 90Y-labeled B72.3 was absorbed rapidly into the plasma with peak levels achieved within 48 h, and levels declined slowly thereafter. Cumulative urinary excretion of the 90Y label was 10-20% of the administered dose which suggests significant whole-body retention of the radiolabel. Biopsy specimens of bone and marrow obtained at 72 h after administration demonstrated significant content of the label in bone (0.015% of the dose/g) with relatively little in marrow (0.005% of the dose/g). The maximal tolerated dose was determined to be 10 mCi because of hematological toxicity and platelet suppression. This typically occurred on the 29th day after administration and was thought to be a consequence of the irradiation of the marrow from the bony deposition of the radiolabel. In an effort to suppress the bone uptake of 90Y, patients were treated with a continuous i.v. infusion of EDTA (25 mg/kg/12 h x 6) infused immediately before i.p. administration of the radiolabeled antibody. Patients (3 pts/dose level) were treated with doses of 10, 15, 20, 25, 30, 35, 40, or 45 mCi of 90Y-labeled B72.3 for a total of 38 patients. EDTA administration resulted in significant myeloprotection, which allowed escalation to the maximal tolerated dose of 40 mCi. Dose-limiting toxicity was thrombocytopenia and neutropenia. Studies of plasma and peritoneal fluid pharmacokinetics demonstrate no changes compared with patients without EDTA pretreatment. Cumulative urinary excretion of the radiolabel was not increased in patients pretreated with EDTA compared with the untreated group. However, analysis of biopsy specimens of bone and marrow demonstrated that bone and marrow content of the 90Y label was 15-fold lower (<0.001% injected dose/g) than a companion group without EDTA. Four responses were noted in patients who received 15-30 mCi of 90Y-labeled B72.3 with response durations of 1-12 months. These results demonstrate the myeloprotective ability of EDTA, which allows safe i.p. administration of higher doses of 90Y-labeled B72.3 and, therefore, clearly warrant an expanded Phase II trial in patients with minimal residual disease after standard chemotherapy or for the palliation of refractory ascites. (+info)
(8/1217) Expression of the hyaluronan receptor, CD44S, in epithelial ovarian cancer is an independent predictor of survival.
Most ovarian carcinomas present at advanced stage, principally as the result of dissemination to peritoneal sites. Standard CD44 (CD44S) is the principal receptor for hyaluronic acid, and in vitro and animal studies have suggested that the attachment of ovarian carcinoma cells to the peritoneal mesothelium involves the interaction between CD44S on ovarian carcinoma cells and hyaluronic acid on mesothelial surfaces. We, therefore, analyzed a series of ovarian carcinomas for the expression of CD44S by immunohistochemistry to see whether expression of this receptor by tumor cells correlated with clinicopathological factors and measures of patient outcome. Fifty-six fixed, paraffin-embedded primary epithelial ovarian tumors were immunostained with antibody to CD44S. Membrane staining was considered positive, and results were correlated with stage, grade, age, histology, and survival. Twenty-two (39%) tumors were positive for CD44S. There was no correlation between CD44 expression and histological type, grade, age, or stage. However, CD44 expression was significantly associated with survival in both univariate (P = 0.003) and multivariate (P = 0.006) analyses. These results support a role for CD44S expression in the spread of ovarian epithelial cancer and suggest that expression of this molecule is a significant independent predictor of survival in women with this disease. (+info)