Changes in apoptotic and mitotic activity in rectal carcinoma after short-term cytostatic therapy as possible predictive factors.

Fifteen patients with rectal adenocarcinoma were endoscopically biopsied and given short-term [5 fluorouracil (5FU) (600 mg/m2) and Ca-Folinate (60 mg/m2) for two days] cytostatic therapy. Seven days later the tumor was resected or a second biopsy was performed. Apoptotic and mitotic indices were determined in the tumor tissue before and after the short-term chemotherapy. The patients were treated thereafter with long-term, intermittent 5 FU administration and followed up clinically for 4-13 months. Three patients showed progression of the disease, twelve improved or showed no tumor progression. An increase of the apoptotic index and decrease of the mitotic index after the short-term cytostatic treatment were seen in the tumor tissue of responder cases. Non-responders showed increase or no change in mitotic activity, and decrease or no change in apoptotic activity. These findings suggest that apoptotic and mitotic response to short-term cytostatic therapy may be additional predictive factor in rectal adenocarcinoma.

[Iatrogenic colorectal perforations--review of cases of the last twenty years]. / Iatrogen colorectalis perforációk--az elmúlt 20 év eseteinek áttekintése.

The experiences with the surgical therapy of 31 patients treated for iatrogenic colorectal perforations during twenty years (1979-1998) are reviewed by the authors. The factors leading to perforation and applied types of operations compared with the therapeutical methods suggested by the literature are summarized. For the treatment of immediately detected instrumental perforations of the well cleaned colon the justification of the suture and primary resection is stressed. The overall lethality, the operative mortality and the rate of perioperative complications were 9.7%, 6.7 and 36.7% respectively.

The relationship between splanchnic oxygen consumption and blood supply.

Our experimental study has proved, that the increase in the intestinal and splanchnic metabolism is associated with raised blood flow. However, it has been found that so called primary increase of the blood flow by the administration of vasodilatators is not associated with raised metabolism, i.e. no increase in the oxygen uptake has been noted. Injection of Glucagon into the superior mesenteric artery raised both the splanchnic (portal vein) and the intestinal (superior mesenteric artery) blood flow. However, while the intestinal oxygen consumption increases along with the blood flow, when the blood flow to the whole splanchnic area has risen the oxygen consumption has not increased moreover it has decreased. This means, that while the Glucagon quickens the metabolism of the small bowel, that in the other abdominal organs has dropped. This means that while there is not any difference in the vascular effect of the intestinal and total splanchnic area, the metabolic effect shows a disparity, this can be regarded as an evidence, that the alterations in the splanchnic metabolism are not primarily determined by haemodynamic changes. The blood flow is adjusted to the oxygen demand and the physiological changes in the blood flow protect against cellular hypoxia under various circumstances.

Effect of acidification of the duodenal contents on splanchnic circulation and metabolism.

Portal vein (PF) and superior mesenteric artery blood flows (SMAF), arterial and portal venous oxygen concentrations were measured in dogs before and after duodenal introduction of 3 ml/kg 0.1 mol HCl. The duodenal acidification increased PF by 30% and SMAF by 35%. The change of mesenteric oxygen utilisation, from 0.80 +/- 0.10 to 0.81 ml/kg was not significant. It is concluded that the circulatory changes after acidification of the duodenal contents are not secondary to a metabolic effect.

Circulatory effects of intraduodenal acidification in the rat.

The effect of intraduodenal administration of 0.3 ml/100 g 0.1 N hydrochloric acid and of the i.v. injection of 0.3 U/100 g secretin on the regional circulation was investigated in rats with the radioactive microsphere method. Intraduodenal acid produced a threefold increase in duodenal blood flow, jejunal perfusion was doubled, the perfusion of pancreas increased significantly. There were no significant changes in cardiac output, renal, myocardial, gastric and ileal blood flow. Secretin administration was without effect on the circulation. The same hormone dose produced a tenfold increase in pancreas secretion but was without effect on bile output. It is concluded that in the rat low doses of secretion do not elicit mesenteric flow changes similar to those observed after duodenal acidification.

The effect of haemorrhage on gastric circulation and acid output in the dog.

Blood flow in the portal vein and the left gastric artery was measured electromagnetically and gastric mucosal perfusion was determined by pertechnetate clearance in anaesthetized dogs. Bleeding the animals to arterial pressures of 100 and 60 mmHg respectively reduced portal venous flow and markedly increased the mesenteric inflow resistance. Left gastric arterial and gastric mucosal blood flow were decreased without significant vascular resistance change only in proportion to perfusion pressure reduction. Gastric acid output decreased but did not stop even at the lower level of haemorrhagic hypotension. It is concluded that ischaemia and acid, probably in the presence of regurgitated bile, may play an important role in the development of stress ulcers.

The effect of duodenal acidification on gastric circulation and function in the dog.

The effect of acidification of duodenal contents on splanchnic bloodflow and gastric circulation was investigated in anaesthetized dogs by measuring electromagnetically portal venous and left gastric artery bloodflow and gastric mucosa bloodflow with pertechnetate clearance. Duodenal acidification increased portal venous bloodflow and reduced mesenteric inflow resistance. At the same time bloodflow in the gastric artery and (not significantly) in the mucosa were reduced in consequence of increased inflow resistances.

The effect of intestinal hormones on splanchnic circulation.

The influence of acidification of the duodenal contents, of intravenous secretin, cholecystokinin and pancreozym injections on hepatic (HAF) and left gastric artery (GAF) and on portal vein blood flow (PVF), bile and pancreatic juice output was studied in dogs. Acid introduction into the duodenum increased HAF and PVF by 20 and 25 percent, respectively. GAF did not change significantly. Secretin and cholecystokinin also increased PVF by 25 percent but HAF changes were less than after acidification. Pancreozym increased significantly only HAF. There were also differences between the effects of duodenal acidification and of the individual hormones on bile and pancreatic juice excretion. It is concluded, that splanchnic circulatory changes observed following duodenal acidification are not produced by the action of a single intestinal hormone but are due to the interplay of several factors.

The mechanism of the changes in splanchnic blood flow after feeding.

Introduction of hydrolysed protein solution into the duodenum increased in the dog hepatic artery and portal venous blood flow. The reaction is, however, smaller than after the introduction of 0.1 N HCl. The introduction of 30% glucose solution has no effect an splanchnic circulation. Splanchnicotomy combined with coeliac ganglion denervation as well as the blockade of the sympathetic alpha receptors abolished the circulatory reaction. Both interventions leads, however, to a decrease is splanchnic vascular resistance similar to that observed after intraduodenal introduction of acid in normal dogs. It is concluded that the circulatory reaction occuring in consequence of the acidifying of duodenal contents after feeding is due to the reduction of abolition of the sympathetic vasomotor tone in the splanchnic vascular bed.

The effect of acidifying the duodenal contents on splanchnic blood flow.

Acidifying the duodenal contents with 0.1 N hydrochloric acid in the dog increased both hepatic artery and portal vein flow, and reduced mesenteric vascular resistance as well as hepatic artery and portal venous inflow resistances. The reaction is absent after intraduodenal injection of 30% glucose and physiological saline solutions. More concentrated acid leads to a greater increase in blood flow. The receptors of the circulatory reflex are situated in the duodenal mucosa and can be blocked with lidocaine.

Estimation of the hepatic blood flow in the dog with the Xe133 and hydrogen wash-out Au190 -colloid uptake techniques and with the electromagnetic flowmeter.

In dogs anaesthetized with pentobarbital hepatic blood flow measured with electromagnetic flowmeters placed on the hepatic artery and the portal vein was 142 +/- 10.2 ml.min(-1).100 g(-1). The flow estimated with the hydrogen clearance technique was 64 +/- 4.4 per cent, with the Xe133 wash-out technique 78 +/- 7.4 per cent and by the uptake of colloidal radiogold 96.5 +/- 5.0 per cent of the direct measurement. In the flow range between 50 and 344 ml.min-1. 100 g-1 the respective correlation coefficient between HBF measured with the hydrogen clearance technique and with the flowmeter was 0.733, between Xe133-HBF and flowmeter HBF 0.785 and between Au198-colloid HBF and the directly measured HBF was 0.815.

Analysis of reflex changes in hepatic tissue blood flow elicited from the intestinal mucosa.

The reflex changes of local hepatic blood flow (HBF) were studied in anaesthetized dogs. An increase of HBF following the acidification of duodenal mucosa and the injection of glucose solution into the intestinal lumen was demonstrated. An attempt was made to cast light on the underlying mechanism which may govern the above mentioned local circulatory reflexes in the liver, by investigating the effect of bilateral vagotomy and of the local anaesthesia of duodenal mucosa. The importance of these hepatic circulatory reflexes from the point of view of surgical indications and the clinical treatment is discussed.