Treatment strategy for synchronous metastases of colorectal cancer: is hepatic resection after an observation interval appropriate?

Background In cases of synchronous colorectal hepatic metastases, the primary colorectal cancer strongly influences on the metastases. Our treatment policy has been to conduct hepatic resection for the metastases at an interval of 3 months after colorectal resection. We examined the appropriateness of interval hepatic resection for synchronous hepatic metastasis. Materials and methods The subjects were 164 patients who underwent resection of hepatic metastasis of colorectal cancer (synchronous, 70 patients; metachronous, 94 patients). Background factors for hepatic metastasis and postoperative results were compared for synchronous and metachronous cases. Results The cumulative survival rate for 164 patients at 3, 5, and 10 years postoperatively was 71.9%, 51.8%, and 36.6%, and the post-resection recurrence rate in remnant livers was 26.8%. Interval resection for synchronous hepatic metastases was conducted in 49 cases after a mean interval of 131 days. No difference was seen in postoperative outcome between synchronous and metachronous cases. Conclusion The outcome was similarly favorable in cases of synchronous hepatic metastasis and in cases of metachronous metastasis. Delaying resection allows accurate understanding of the number and location of hepatic metastases, and is beneficial in determining candidates for surgery and in selecting surgical procedure.     

Epinephrine is an enhancer of rat intestinal absorption.

Some physiological substances, including acetylcholine and nitric oxide, are useful candidates for stimulation of intestinal absorption of drugs. In the present study, we elucidated the ability of epinephrine (Epi) to stimulate the intestinal absorption of drugs. We evaluated the ability of Epi to enhance absorption of macromolecules using dextran (Mw 4000 Da), which is poorly absorbed from the intestine, as a model compound in situ in a closed loop of the rat jejunum. Treatment of the jejunum with Epi resulted in significant increase in absorption of dextran in a dose-dependent fashion. The area under the curve (AUC) from 0 to 4 h in the Epi-treated jejunum was 13-fold higher than that in the vehicle-treated jejunum. The absorption-enhancing activity of Epi was 40-fold higher than that of caprate, a clinically used absorption-enhancer of drugs. In the experimental conditions used in this study, histological injury of the mucosa and perturbation of the mucosal membrane were not observed in the Epi-treated jejunum. Treatment with an antagonist of alpha-adrenergic receptors attenuated the stimulation of intestinal absorption by Epi, and treatment with an agonist of alpha-adrenergic receptors resulted in enhancement of intestinal absorption. While an antagonist of beta-adrenergic receptors enhanced the absorption-enhancing effect of Epi, an agonist of beta-adrenergic receptors stimulated intestinal absorption. These results indicate that stimulation of adrenergic receptors may be a novel strategy for intestinal absorption of drugs.     

Heterogeneous distribution of muscarinic receptors in the rabbit saphenous artery.

1. The properties of the muscarinic receptors in the rabbit saphenous artery were determined from electrical and mechanical responses of smooth muscle cells produced by acetylcholine (ACh). The inhibitory action of atropine and pirenzepine on the ACh-induced responses was also studied. 2. ACh produced a transient hyperpolarization of the membrane and inhibited the noradrenaline (NA)-induced contraction. These effects of ACh were apparent only when the endothelial cells were intact. 3. The ACh-induced transient hyperpolarization was antagonized by atropine or pirenzepine, with similar potencies (the ID50 values were about 2 x 10(-8) M for both antagonists). 4. The ACh-induced inhibition of the contraction to NA was antagonized by atropine more preferentially than by pirenzepine (the ID50 values were 2 x 10(-8) M for atropine and 10(-6) M for pirenzepine). 5. The excitatory junction potential (e.j.p.) evoked by perivascular nerve stimulation was inhibited by ACh (above 10(-8) M). The ACh-induced inhibition of the e.j.p. was antagonized by atropine more preferentially than by pirenzepine (the ID50 values were 3 x 10(-8) M for atropine and 6 x 10(-6) M for pirenzepine). 6. It is concluded that in the rabbit saphenous artery, two subtypes of muscarinic receptor (M1 and M2) are located on the endothelial cells. Stimulation of each subtype releases a different substance, i.e., a hyperpolarizing substance (M1-subtype) or a relaxant substance (M2-subtype). In prejunctional nerve terminals, the muscarinic receptors responsible for inhibiting the release of transmitter substances are of the M2-subtype.