Prophylaxis of venographically diagnosed deep vein thrombosis in gastrointestinal surgery. Multicentre trials 20 mg and 40 mg enoxaparin versus dextran.

OBJECTIVE: To compare enoxaparin and dextran 70 for the prophylaxis of venographically diagnosed deep vein thrombosis (DVT) after gastrointestinal operations. DESIGN: Part 1: randomised double blind trial; Part 2: single blind study with historical controls. SETTING: Eight Norwegian hospitals. SUBJECTS: 381 Patients undergoing elective gastrointestinal operations. INTERVENTIONS: Part 1 (n = 329): enoxaparin 20 mg subcutaneously starting two hours before operation and continuing until the patient was fully mobilised or had had 10 injections and a placebo infusion of 0.9% sodium chloride, or dextran 70,500 ml at the start of the operation, on the evening of operation, and on the first, third, and fifth postoperative days and placebo subcutaneous injections. Part 2 (n = 52): enoxaparin 40 mg in the same regimen as part 1 (compared with 39 historical controls). Venograms 4-6 days post-operatively. MAIN OUTCOME MEASURE: Venographically confirmed DVT. RESULTS: Part 1: Because of the high overall incidence of DVT an interim analysis was done which showed 33/101 DVT (33%) among high risk patients in the enoxaparin 20 mg group and 33/107 (31%) in the dextran 70 group. The corresponding figures for patients at medium risk were 2/27 (7%) for enoxaparin 20 mg and 5/27 (19%) for dextran 70 (95% confidence interval (CI) for the difference--11.9 to 9.8). Part 2: the dose of enoxaparin was therefore increased to 40 mg and prophylaxis restricted to patients with cancer. There were 6/49 DVT (12%), which was compared with a random sample from the dextran 70 group from part 1 (historical controls) in which the incidence was 15/39 (38%, 95% CI of the difference 4.0 to 8.4). There were no pulmonary emboli, only 4 thrombi were above the knee and there were 4, 1 and 3 clinical DVT in the 20 mg and 40 mg enoxaparin, and dextran 70 groups, respectively. CONCLUSIONS: Enoxaparin 20 mg and dextran 70 are effective prophylaxis for patients at medium risk, but enoxaparin 40 mg is required for those at high risk.

Prospective randomized study of routine intraoperative cholangiography during open cholecystectomy: long-term follow-up and multivariate analysis of predictors of choledocholithiasis.

A prospective randomized study was performed to assess the value of routine intraoperative cholangiography (IOC) during cholecystectomy for gallstone disease. Four hundred and fifty-seven consecutive patients were screened for the presence of 11 predefined clinical criteria assumed to indicate choledocholithiasis. Two hundred and eighty patients who had no positive criteria and in whom preoperative endoscopic retrograde cholangiography had not been performed were randomized at the operating table to the IOC or no-IOC group. Follow-up was performed 6 to 8 years after the operation with a questionnaire and by use of clinical, biochemical, and radiologic investigations as indicated. Multivariate analysis was used to identify independent predictors of choledocholithiasis and the combination of criteria having the best predictive ability. The frequency of common bile duct calculi at operation was significantly correlated with age and with all clinical criteria except recent or present pancreatitis. However, only serum bilirubin level, cystic duct diameter, demonstration of common bile duct calculi on preoperative imaging or intraoperative palpation, and age at operation were independent predictors of choledocholithiasis. The overall best subset of clinical indicators contained all criteria with the exception of pancreatitis and alkaline phosphatase level. Negative predictive ability of the set of criteria was 100% for patients up to 60 years of age and 97% for patients older than 60 years at the time of operation. No case of residual common bile duct calculi was present in the IOC and no-IOC groups at follow-up. Our data strongly support a policy of performing IOC during cholecystectomy only when clinical criteria suggest the presence of common bile duct abnormalities or to clarify ductal anatomy.

Serum carcinoembryonic antigen in relation to survival, DNA ploidy pattern, and recurrent disease in 406 colorectal carcinoma patients.

Serum carcinoembryonic antigen (CEA) levels in relation to survival, flow cytometric DNA ploidy pattern, Dukes stage, and recurrent disease was prospectively evaluated in 406 patients with colorectal carcinoma. In 246 patients (61%) the carcinomas were DNA aneuploid. Increased preoperative CEA levels (> 5 micrograms/l) were found in 151 of 363 evaluable patients (42%). Dukes stage-B patients with preoperative CEA elevation showed significantly poorer prognosis than those with normal CEA values (p = 0.001). A weak but significant correlation was found between preoperative CEA level and Dukes stage (Kendall's tau = 0.25, p < 0.01). Of 50 evaluable patients with clinical recurrence and postoperative normal or normalized CEA levels, 28 (56%) had a rise in CEA before or at the time of clinical recurrence. The sensitivity of the CEA test for primary and for recurrent disease was not significantly different in the DNA aneuploid and the DNA near-diploid groups.

Association between DNA ploidy pattern and cellular atypia in colorectal carcinomas. A new clinical application of DNA flow cytometric study?

Fresh tissue specimens from 406 colorectal carcinomas were analyzed by DNA flow cytometric study, and the DNA ploidy pattern was compared with Dukes' stage, histologic grade, and degree of cellular atypia. Sixty-one percent of the carcinomas had a distinct aneuploid DNA pattern. The proportion of aneuploid carcinomas was significantly higher in the advanced Dukes' stages than in the localized ones. A highly significant association was found between DNA ploidy pattern and degree of cellular atypia, whereas no association was demonstrated between DNA ploidy pattern and histologic grade. This finding might indicate that cellular atypia has a stronger prognostic impact than the growth pattern of the tumor. The authors suggest that flow cytometric DNA quantification may replace assessment of cellular atypia in the histologic evaluation. Furthermore, together with earlier findings by others, these results indicate that the degree of cellular atypia may be conserved during the development from adenomas to carcinomas.

Predictive ability of choledocholithiasis indicators. A prospective evaluation.

To assess the predictive ability of various indicators of common bile duct calculi, 457 patients undergoing cholecystectomy for gallstone disease were prospectively screened for the presence of 11 predefined criteria of possible choledocholithiasis. The predictive ability of the criteria, individually and in combinations, was determined. For all criteria, except a history of pancreatitis, a significantly increased incidence of choledocholithiasis was found. The number of positive criteria correlated positively with the frequency of common bile duct calculi. The negative predictive value and sensitivity of the total set of criteria were 98% and 89.5%, respectively. Following common duct exploration, the number of complications and the duration of postoperative hospitalization were significantly increased as compared with simple cholecystectomy. Peroperative cholangiography with cholecystectomy is recommended in all patients, with one or more criteria of possible choledocholithiasis. Routine peroperative cholangiography in patients with no positive criteria does not seem to be necessary.

Clinical significance of carcinoembryonic antigen (CEA) in patients with adenocarcinoma in colon and rectum.

Determination of carcinoembryonic antigen (CEA) in serum has been performed in 253 patients with proved adenocarcinoma in the colon and rectum. Preoperative CEA was normal in 58.3% of the patients. A correlation between CEA level and Dukes' grading was found. There was, however, no statistically significant difference in recurrence rate between patients with normal and patients with elevated pre-operative CEA. Transient CEA elevation was seen in the follow-up period after curative resection in 21.8%. 75% of the patients with recurrence had abnormal CEA, and CEA elevation was the first sign of recurrence in 59.1%. The majority of these patients, however, had advanced disease not available for surgical treatment. In cases with local resectable tumour CEA often was normal. Only a few patients had advantage of CEA determination for diagnosis of recurrence and its routine use is therefore questioned.

Nonoperative internal drainage of obstructive common bile ducts.

A new nonoperative method for internal drainage of common bile duct obstructions by endoscopic retrograde cannulation of the papilla of Vater is described. After introduction of a tube in the common bile duct, a substantial decrease in serum activity of bilirubin, alkaline phosphatase, and gamma-glutamyl transferase was found. In addition, a rapid improvement of the clinical condition could be observed. No serious complications occurred. It is concluded that internal drainage of common bile duct obstructions might be of great value in the preoperative treatment of patients with common bile duct obstructions.

The value of preoperative haemostatic screening.

The value of preoperative haemostatic screening tests in prediction of surgical bleeding was examined in 101 patients, mainly with abdominal and thyroid lesions. The study demonstrated complete lack of correlation between the preoperative evaluation of bleeding risk and the observed surgical bleeding (phi2 test P approximately 0.85).