Coagulation inhibition and activation in pancreatic cancer. Changes during progress of disease.

BACKGROUND: To elucidate the disturbed hemostatic balance in patients with pancreatic cancer, the levels of plasma coagulation inhibition and coagulation activation were determined. METHODS: Twenty-one patients with adenocarcinoma of the pancreas were followed from time of diagnosis until death, using plasma analyses of coagulation inhibitors and a molecular marker of coagulation activation (thrombin-antithrombin complex, TAT). RESULTS: TAT was increased significantly at the time of diagnosis of pancreatic cancer compared with age-adjusted healthy control subjects (mean, 6.2 +/- 4.6 micrograms/l [standard deviation] versus 2.0 +/- 0.7 micrograms/l). It increased with disease progression (mean in the terminal phase, 14.1 micrograms/l; P < 0.05). Plasma levels of tissue factor pathway inhibitor (TFPI) also were increased significantly at the time of diagnosis compared with the control group (mean, 176 +/- 80% versus 127 +/- 29%; P < 0.05). The TFPI decreased to normal levels (121 +/- 40%) after surgical removal of the pancreatic tumor (n = 4) or relief of the cholestasis using a bypass procedure (n = 6). The TFPI levels increased significantly as the malignant disease progressed (from 1-3 months postoperatively to the terminal phase of disease; mean, 114 +/- 52% versus 154 +/- 60%). There was a significant positive correlation between TFPI levels and bilirubin levels; the correlation coefficient at diagnosis was 0.70 (P < 0.001). The levels of the coagulation inhibitors antithrombin, heparin cofactor II, protein C, and free protein S decreased significantly with disease progression compared with the normal values found at diagnosis. CONCLUSIONS: The mechanism for TFPI increase in cancer is not known. It may be related to the preoperative cholestasis seen in this study, but the increased degree of coagulation activation also may contribute.

[Esophageal cancer. Treatment and results]. / Cancer oesophagi. Behandling og resultater.

Between 1979 and 1989, 38 patients were treated for cancer of the oesophagus. 25% (21/38) of the patients underwent resection of the oesophagus with either curative or palliative measures. 12 patients were treated radically, of whom two (17%) have lived free of recurrence for more than five years. Radical thoracoabdominal oesophageal resection is recommended as long as the operative mortality is low. Careful preoperative evaluation is necessary to select patients who should be treated by palliative procedures, such as oesophageal resection, by-pass procedures, laser coagulation and/or local irradiation.

High plasma levels of extrinsic pathway inhibitor and low levels of other coagulation inhibitors in advanced cancer.

Serial determinations of plasma coagulation inhibitor levels were performed with chromogenic substrate activity assays in 7 patients with cancer. At time of diagnosis normal median activities of Antithrombin, Protein C, Heparin Cofactor II and Extrinsic Pathway Inhibitor were found. The inhibitor activities changed significantly with the progress of malignant disease; Antithrombin, Protein C and Heparin Cofactor II decreased whereas Extrinsic Pathway Inhibitor increased. Determinations in 13 additional patients in the terminal phase of cancer confirmed this finding. The inhibitor activities were expressed in per cent of a pooled reference plasma. In the total series of 20 patients studied, median activity of Extrinsic Pathway Inhibitor was 183% (range 61-378%) and significantly (p less than 0.005) above age-adjusted normal reference 10 days (range 1-20 days) prior to death. Median activities of Antithrombin was 59% (range 20-109%), of Protein C 54% (range 24-130%) and Heparin Cofactor II 59% (range 33-110%), all significantly below age adjusted normal reference (p less than 0.001). The coagulation inhibitor levels seem related to the stage of disease in patients with cancer.

The surgical treatment of gastric cancer: a retrospective study with special reference to total gastrectomy.

A retrospective study of 312 consecutive cases of gastric malignancy treated from 1974 to 1984 is presented. Eighteen patients (6%) had gastrointestinal lymphoma of the stomach. Among the remaining 294 cases with gastric carcinoma, 46 (16%) had carcinoma of the gastric stump after previous resection for peptic ulcer. Fifty-seven percent (167/294) had no distant metastases (MO). Early gastric carcinoma (pT1) occurred in 16 patients (5.8%), among whom four had distant metastases (pT1M1) and another two patients had regional lymph node metastases (pT1N1). Thirty-three percent of the patients had either no surgical treatment or an explorative laparotomy only, and 9% had a palliative bypass operation performed. A curative (48%) or palliative (10%) resection of the stomach was possible in 171/294 patients. Thus, the resectability rate was 58%. Total gastrectomy was performed in 108 cases with either curative (100) or palliative (eight) intention. The 30-day mortality was two and one patients, respectively (2.8%). Crude survival in the whole series was 16% and 11% at 5 and 10 years. After non-randomized curative total gastrectomy (100 cases) or gastric resection (40 cases) crude survival was 40% and 22% at 5 years, and 24% and 16% at 10 years, respectively (P greater than 0.05, n.s.). We found that total gastrectomy with extensive dissection and end-to-end esophago-jejunostomy by the EEA stapler can be performed with a low mortality rate (2% after curative operation) even in the upper age groups.

The influence of preoperative drug treatment on the histological appearances and in vitro 131I uptake of human hyperplastic thyroid gland.

The specimen of thyroid resected at partial thyroidectomy from 103 patients with primary thyrotoxicosis was studied with histometric and organ culture techniques. Twenty-seven patients had been prepared for operation with propranolol and seventy-six with carbimazole: all received Lugol's iodine for 10 days before operation. The resected specimen and deduced total thyroid weight was greater in the patients prepared with carbimazole. There was no absolute qualitative histopathological difference in the appearance of the glands of the two groups of patients, but histometry showed that the volume percentage of colloid and total gland colloid weight was significantly greater in the patients prepared with carbimazole: the volume percentage of epithelial cells and the total gland epithelial cell weight was similar in the two groups. The iodide concentrating capacity per g wet weight thyroid tissue or per unit volume of colloid did not differ significantly between the two groups. However, the iodide concentration capacity per unit volume of epithelial cells was significantly higher in the carbimazole prepared patients than in those prepared with propranolol.