Adjuvant chemotherapy with 5-fluorouracil, vincristine and CCNU for patients with Dukes' C colorectal cancer. The Swedish Gastrointestinal Tumour Adjuvant Therapy Group.

A prospective controlled randomized trial testing adjuvant postoperative combination chemotherapy (5-fluorouracil, lomustine (CCNU) and vincristine) versus no adjuvant therapy in patients operated on for Dukes' C colorectal cancer is reported. In total 334 patients aged less than 70 years were recruited: 205 patients with colonic and 99 with rectal cancer, but there were three protocol violations and these cases are excluded from further consideration. Twenty-seven patients had a limited resection of their cancer. After 5 years' follow-up there was no significant difference in the tumour-free survival rate or in the survival rate between the treated and control groups. Twenty-nine of the 147 patients who started chemotherapy discontinued this treatment because of side-effects, mainly from the gastrointestinal tract. In 30 patients treatment was discontinued because of recurrent disease. The conclusion is that systemic administration of combination chemotherapy for colorectal cancer after operation is not worthwhile in routine clinical practice.

The effects of omeprazole and cimetidine on duodenal ulcer healing and the relief of symptoms.

In a Swedish double-blind multicentre study, omeprazole (30 mg o.m.) was compared with the H2-receptor antagonist cimetidine (400 mg b.d.) in 152 patients. Clinical assessments and laboratory investigations were carried out at 2 and 4 weeks, and again at 6 weeks in unhealed patients. Endoscopy was performed at 2 weeks, and again at 4 and 6 weeks in unhealed patients. The patients in the two groups were well-matched prior to treatment. Omeprazole was superior to cimetidine in ulcer-healing rate after 2, 4 and 6 weeks. After 2 weeks of treatment, 66% of the omeprazole- and 45% of the cimetidine-treated patients were healed (P = 0.02), after 4 weeks 97 and 84% (P = 0.01), and after 6 weeks 100 and 92% (P = 0.02), respectively. There was a more pronounced improvement in the patients' symptoms in the omeprazole group after 2 weeks (P = 0.05). Both drugs were well-tolerated, but there was a high prevalence of patients with adverse events in the cimetidine group (51%, compared to 30% of the omeprazole group; P = 0.02). A total of 125 patients were followed for 6 months after healing. The patients were investigated by endoscopy after 6 months, or whenever symptoms occurred. There was no significant difference in the rate of relapse within 6 months between the two treatment groups: 54% relapsed in the omeprazole group and 52% in the cimetidine group. In conclusion, 30 mg of omeprazole, given once daily, is superior to 400 mg of cimetidine twice daily in duodenal ulcer healing; but ulcer relapse in the two groups appears to be equivalent.

Squamous-cell metaplasia with severe dysplasia of the colonic mucosa in ulcerative colitis. Report of a case.

Squamous-cell metaplasia in the colonic mucosa alone in ulcerative colitis has not been reported before. A case is presented where such changes were found in relation to strictures in the transverse and sigmoid colon in a male, aged 41, with a 27-year history of ulcerative colitis.

Pregnancy after jejuno-ileostomy because of obesity.

In four cases of pregnancy after jejuno-ileostomy because of massive obesity intestinal absorption was adequate for the nutrition of both the baby and the mother. It appears that such an operation because of obestiy does not contraindicate later pregnancy; In one case postoperative loss of body weight probably made pregnancy possible. In extremely adipose women who are for some unknown reason infertile and wish to have a child a shunt operation might perhaps be offered.

Superior mesenteric angiography and blood flow following intra-arterial injection of prostaglandin F2alpha.

The effect of intra-arterially administered prostaglandin F2alpha(PGF2alpha) on venous demonstration in angiography of the superior mesenteric artery was compared to that of bradykinin in 10 patients, and the flow increase in this vessel following PGF2alpha was measured by a dye dilution technique in another 8 patients. The angiographic demonstration of veins was similarly improved by the 2 drugs, the effect of 60 mug. of PGF2alpha being roughly equivalent to that of 10 mug. of bradykinin. The loss of arterial detail was less marked after PGF2alpha which, however, had a longer duration of action. The flow studies indicated that 80 mug. of PGF2alpha increased the superior mesenteric blood flow 103 +/- 16 per cent. There was no influecne on blood pressure or pulse rate. The patients experienced a sensation of warmth in the abdomen for a few seconds following the injection of drugs, but no other side effect was noted. It is concluded that PGF2alpha causes a rapid increase of the superior mesenteric blood flow in man making it suitable for pharmacoangiography of this vascular bed.

Superior mesenteric blood flow during experimentally induced dumping in man.

The superior mesenteric circulation was studied with a dye-dilution technique after catheterization of the superior mesenteric artery and vein during provoked dumping in 5 patients. Dumping was provoked by intrajejunal instillation of 150 ml 50% glucose. A marked increase of, on the average, 157% was recorded in the superior mesenteric blood flow within a few minutes of the installation of glucose. The maximal increase in the flow was, on the average, 223% and occurred about 40 minutes after provocation. The instillation of glucose was promptly followed by a reduction in vascular resistance of the superior mesenteric vessels by 63% which decreased further to a mean maximal reduction of 76% below the resting level. The increase in the ratio between the superior mesenteric blood flow and cardiac output from 12 to 27% following instillation of glucose further underlines the pronounced vasodilatation of the small intestine. Superior mesenteric angiography at different intervals after provocation of dumping showed that the increased superior mesenteric blood flow is due to a local increase in the flow.

Superior mesenteric blood flow during digestion in man.

The superior mesenteric blood flow was studied with a dye-dilution technique after catheterization of the superior mesenteric artery and vein during the digestive phase after intake of a mixed meal (700 kcal). The material consisted of 5 patients. Within 5 minutes of the end of the meal the superior mesenteric blood flow, on the average, was increased by 60%. The largest increase was 113% and was noted one hour after the meal. The vascular resistance of the superior mesenteric vessles had by then fallen to a mean value of 55% below the prefeed value. The portal venous pressure was only slightly increased. The cardiac output was increased in 2 but slightly decreased in the remaining 3 patients. The pulse rate, blood pressure and haemoglobin concentration were largely unchanged. The ratio of the superior mesenteric blood flow to the cardiac output increased from 12 to 22% during the digestive period. The findings suggest the occurrence of a redistribution of blood after a meal with an increase in the superior mesenteric blood flow.

Superior mesenteric blood flow in man studied with a dye-dilution technique.

The superior mesenteric blood flow in the post-absorptive state was studied with a dye-dilution technique using indocyanine green in 37 patients with apparently normal small bowel function. All the patients except 2 had been, or were to be, treated because of malignant disease, mostly rectal carcinoma. The investigations were performed in connection with portography. The dye was injected into the superior mesenteric artery as a single injection during continuous sampling of blood from the superior mesenteric vein, catheterized through the reopened umbilical vein. The blood flow was calculated from the dye-dilution curves obtained with a modified Stewart-Hamilton formula. As recirculating dye appeared in the later part of the dye-dilution curves, the appearance of the recirculating dye was timed in 4 patients. The hepatic extraction of the amount of dye usually injected, 1.25 mg, was 60%. The superior mesenteric blood flow averaged 706 ml/min (397 ml/min/m-2 body surface) or 12% of the cardiac output. The appearance time, mean transit time, vascular resistance and vascular volume were also determined.

Superior mesenteric blood flow in man following injection of bradykinin and vasopressin into the superior mesenteric artery.

The superior mesenteric blood flow was studied with a dye-dilution technique after catheterization of the superior mesenteric artery and vein. The investigation was performed in connection with portography in 22 patients with apparently normal small bowel function. Intra-arterial injection of 5, 10 or 20 mug bradykinin was followed within one minute by an increase, on the average, of 114, 176 and 223% respectively, in the superior mesenteric blood flow. The blood flow was dose-dependent in this range. The estimated vascular resistance decreased by 52, 61 and 67%, respectively. The portal venous pressure was increased slightly after intra-arterial injection, but the pressure was unchanged after intra-portal injection. Intra-arterial injection of bradykinin causes a highly improved venous phase at superior mesenteric angiography. This may be due not only to the increased flow but to some extent also to increased capillary permeability produced by bradykinin. Intra-arterial injection of 0.125 and 0.250 IU of vasopressin decreased the superior mesenteric blood flow by 53 and 54%, respectively, within 3 minutes of the injection. The dye-dilution method used was not applicable to blood flow below a level of about 200 ml/min. Continuous infusion of 0.05 IU/min decreased the superior mesenteric blood flow by, on an average, 58%. The portal venous pressure was decreased by 25% after the intra-arterial injection, but no change in pressure was recorded after intra-portal administration. The clinical use of intra-arterial infusion of vasopressin during gastrointenstinal bleeding is discussed.

Gastrin in portal and peripheral venous blood after feeding in man.

The concentrations of immunoreactive gastrin in serum from portal and peripheral venous blood were determined in 10 patients with indwelling portal catheters before and after feeding. No significant differences were found between the gastrin concentrations in portal and peripheral serum. Gel filtration studies of serum did not reveal any differences between the gastrin components of portal and peripheral venous serum. Since neither the concentrations of immunoreactive gastrin nor the four gastrin components differed between portal and peripheral serum it is suggested that the liver is without effect on gastrin metabolism.