No abstract

Seventy-four previously untreated patients with metastatic colorectal adenocarcinoma were prospectively randomized into one of three treatment regimens: (1) 5-fluorouracil (5-FU) 450 mg/m2 as an intravenous (IV) bolus daily for five days or toxicity, then 200 mg/m2 IV bolus every other day for six doses; (2) methotrexate (MTX) 50 mg/m2 in normal saline by IV infusion over four hours followed by an IV bolus of 5-FU 600 mg/m2. This was administered weekly for 4 weeks and then every 2 weeks. (3) Leucovorin 500 mg/m2 in a two-hour IV infusion of normal saline with 5-FU 600 mg/m2 as an IV bolus one hour after the Leucovorin began every week for 6 weeks. The combined complete and partial response rates in the three regimens were 11%, 5%, and 48%, respectively (P = .0009). The median duration of response in the 5-FU and Leucovorin regimen was 10 months. There was no statistically significant difference between the treatment regimens with respect to survival time (P = .6). Toxicity in the 5-FU and Leucovorin regimen was predominantly diarrhea (13 of 30 patients, 40%). In this regimen, eight of 13 patients (52%) who developed diarrhea not only required a dose reduction of 5-FU, but also hospitalization for IV hydration. The predominant toxicity in the 5-FU alone regimen and the 5-FU and MTX regimen was leukopenia. One drug-related death occurred in each regimen.

Since its introduction the Wessler stasis rabbit model (Wessler, et al. J. Appl. Physiol. 14:(6), 943, 1959) has been widely used in the evaluation of the thrombogenic properties of prothrombin complex concentrates (activated and non-activated) and antithrombotic effects of various drugs. In order to study the antithrombotic actions of low molecular weight fractions and oligosaccharide fragments we used a modified stasis (rabbit) model with thrombogenic stimuli which produced a marked increase in circulating factor Xa levels. Male New Zealand rabbits ranging from 23 kg were injected (subcutaneous) with an analgesic muscle relaxant, xylazine (20 mg/kg) followed by ketamine (80 mg/ kg). Prothrombin complex concentrate (PCC) is injected within 2 minutes into a contralateral rabbit ear vein (25 units/kg) immediately followed by Russell’s viper venom (RVV). Within varying times after completion of the infusion, (1-15 minutes) previously exposed right and left jugular veins were gently isolated, kept in situ for 10 minutes, carefully excised and the clot formed was graded. Only minor changes were observed in the coagulation profile after the PCC/RW infusion, however measurable clots in both segments of the isolated vein were seen. Intravenous injection of heparin fractions (<500 μg/kg) and oligosaccharide fragments (<100 μg/kg)blocked the thrombotic effects of PCC/RW mixture in both the pretreatment and post-treatment regimens, whereas heparin at 500 μg/kg failed to show any antithrombotic effects. Bovine and human factor Xa concentrates, tissue thromboplastins, human serum, human and bovine a-thrombin, and arachidonic have also been employed as thrombogenic stimuli. Our studies show that the modified stasis rabbit model offers definite advantages over the existing model and provides a suitable in vivo standardized model to test antithrombotic effects of newly developed heparin fractions and fragments with high anti Xa and low anticoagulant action.

A retrospective analysis of the prognostic significance of anastomotic recurrence in 50 patients with colorectal adenocarcinoma was conducted from 1970 to 1987. All primary cancers were located above 10 cm from the anal verge. Forty anastomotic recurrences (80 percent) followed resection of sigmoid or proximal rectal tumors. The overall disease-free interval was 13 months, with 90 percent of recurrences diagnosed within 24 months of the primary resection. Forty-five recurrences (90 percent) were associated with synchronous or metachronous metastases. Overall median survival following the recurrence was 16 months--37 months if the anastomosis was the only recurrence site. Of five patients alive without evidence of disease, all were asymptomatic, and recurrence was confined to the anastomosis. In conclusion, anastomotic recurrence following resection of colorectal adenocarcinoma frequently heralds disseminated disease but can be potentially resected for cure if it is the only site in an otherwise asymptomatic patient.

The records of 237 patients treated for benign and malignant villous and tubulovillous adenomas at Roswell Park Memorial Institute from 1963 to 1987 were reviewed. Sixty-five adenomas were greater than or equal to 4 cm and form the basis of this report. Fifteen (23%) were in the cecum, 3 (5%) in the right colon, 1 (1%) in the splenic flexure, 10 (15%) in the sigmoid colon, and 36 (55%) in the rectum. The most common symptoms were rectal bleeding (70%), mucus diarrhea (44%), constipation (22%), and tenesmus (19%). Fifty-five (85%) of these large adenomas contained invasive adenocarcinoma and one in situ carcinoma. Two thirds of invasive carcinomas arose from predominantly villous adenomas and one third from tubulovillous adenomas. Half of all malignant adenomas demonstrated metastases to regional lymph nodes or distant metastases. Seven malignant adenomas (12%) were associated with synchronous adenocarcinomas of the colon, and 29% of malignant adenomas were associated with synchronous adenomatous polyps, principally tubular type. Four of nine benign, large adenomas were associated with synchronous adenomas but with no adenocarcinomas. No relationship was found between the size of the adenoma, location, or Dukes' stage. Though the incidence of in situ and invasive carcinomas is clearly related to the size of the adenoma, a linear relationship could not be demonstrated.