Fourteen patients with liver tumor malignancy and sixteen patients with malignant melanoma localized to one limb were studied regarding leukocyte activation with the release of polymorphonuclear neutrophilic (PMN) elastase and of neopterin and formation of cytokines (TNF-alpha and IL-6) during the surgical treatment. Patients undergoing liver resection (n = 10), abdominal hysterectomy (n = 10), or hip replacement surgery (n = 10) served as control groups. Isolated hyperthermic liver perfusion was performed with cytostatic-containing perfusate (melphalan and cisplatinum). Patients with recurrent malignant melanoma confined to one limb underwent isolated hyperthermic limb perfusion with cytostatic-containing perfusate (melphalan). Blood samples for determination of PMN elastase, neopterin, TNF-alpha, and IL-6 were drawn from the patients preoperatively, 1 minute before the start of the perfusion, 60 and 120 minutes after the start of the perfusion, and 24 hours postoperatively. Samples from the perfusate were drawn 60 minutes after the start of the perfusion. High concentration of plasma PMN elastase were found in both patients undergoing liver and limb perfusion and in patients undergoing liver resection surgery. Elevated concentrations of IL-6 were found in the patients undergoing liver perfusion and in patients undergoing liver resection. In none of the patients were there increased concentrations of neopterin or TNF-alpha. The perfusate contained high concentrations of PMN elastase, neopterin, and IL-6. This study also demonstrated that major surgery leads to elevated concentrations of PMN elastase and IL-6. An increase of PMN elastase and IL-6 was seen in response to perfusion and to surgical trauma.

Adult↗

PubMedDate not supplied

Blood flow in liver tumors--effects of vasoactive drugs estimated with xenon (133Xe) clearance.

BACKGROUND/AIMS: The aim of the present study was to identify in a standardized experimental rat liver tumor system the drugs which are most appropriate in influencing the relationship between liver tumor and normal liver parenchyma blood flow as estimated with 133Xe washout clearance method, and thereby positively influencing the kinetics of chemotherapeutic drugs. A battery of vasoactive drugs, which according to a literature review were considered to be active, were tested. METHODOLOGY: Twelve drugs were administered intravenously on 113 Wistar-Fu rats with an experimental adenocarcinoma in the liver (weight 0.62 g). 133Xe was applied in the tumor and in normal parenchyma with and without administration of a vasoactive drug. The pulses were registered with a NaI (Tl)-scintillation detector connected to a multichannel analyzer. The disappearance rate of the isotope was calculated according to a single compartment model. Four recordings were performed in each rat randomly in tumor and liver parenchyma with and without a drug (series A) and one series twice in tumor and twice in parenchyma with a drug (series B). RESULTS: In unaffected animals the tumor to liver quotient was 0.57+/-0.35. This quotient was higher in tumors less than 0.53 g. Angiotensin-II 8 mg i.v. increased the quotient to 0.95+/-0.20. No other drug significantly influenced the quotient. CONCLUSIONS: In an experimental adenocarcinoma in the liver this study has investigated the possibility of increasing the tumor to normal liver parenchyma blood flow quotient by a variety of vasoactive substances for the beneficial modification of tumor blood flow. Angiotensin II 8 mg i.v. was the only drug, which increased the quotient. None of the other tested drugs were supporting previous presented results on influencing tumor blood flow.

Animals↗

PubMedDate not supplied

Cytotoxicity of liver macrophages against liver tumours. Influence of betamethasone, indomethacin and allopurinol.

Macrophage activation with zymosan has an inhibitory effect on tumour take and initial tumour growth in the rat liver. 91 rats with syngeneic transplanted hepatoma in the liver were treated with zymosan (46) or saline (45). Betamethasone (glucocorticoid), indomethacin (prostaglandin synthesis inhibitor), allopurinol (oxygen radical scavenger) or saline were administered concomitantly. Tumour take, tumour growth and relative spleen weight were used as in vivo parameters of liver macrophages cytotoxicity and general macrophage activation. Zymosan inhibition of tumour take was counteracted by betamethasone, indomethacin and allopurinol. Betamethasone increased the growth rate of the non-zymosan treated tumours during seven days. Indomethacin decreased the growth rate of the tumours in non-zymosan treated rats up to 14 days. Allopurinol significantly blocked the zymosan inhibition of tumour take and tumour growth after 7 and 14 days. Allopurinol blocked zymosan induced increased relative spleen weight. It is proposed that the liver macrophage cytotoxicity induced by zymosan is in part mediated via production of oxygen radicals.

Allopurinol↗

PubMedDate not supplied

Tumour adjacent macrophage function in experimental tumours.

This study describes in vivo methodology for evaluating whole body and Tumour Adjacent Macrophage (TAM) phagocytic function in tumour-bearing rats. 29 Wistar rats were inoculated with 1 x 5 mm cylinders of syngeneic NGW-adenocarcinoma im in the right hind leg. 10 rats were given iv zymosan (3mg/100 g b.w.) for systemic activation of macrophages, 9 rats were given intratumour injection of zymosan (3mg/100g b.w.) for local activation and 10 rats were untreated controls. 10 days after tumour inoculation whole body phagocytic rate was estimated with dynamic liver RES scintigraphy. Tumour and blood radionuclide activity was measured. Dynamic liver RES scintigraphy measures whole body macrophage phagocytic rate (k) of iv 99Tcm Nanocoll albumin test colloid. TAM phagocytic rate is calculated from the final uptake in tumor/injected dose x k. Systemic macrophage activation caused a significant increase in liver and spleen weight and whole body phagocytic rate (0.65 +/- 0.02 versus 0.56 +/- 0.03% s-1). The TAM phagocytic rate was significantly elevated in tumors treated by local macrophage activation (0.003 +/- 0.00 versus 0.001 +/- 0.00% s-1). This study suggests that the TAM phagocytic rate is a sensitive indication of local macrophage activity.

Adenocarcinoma↗

PubMedDate not supplied

RES-macrophage stimulation and liver tumour growth in rats; evaluation with dynamic liver RES scintigraphy.

Dynamic liver RES scintigraphy with Nanocoll (99Tcm albumin colloid - 50 nm diameter) assessing RES-macrophage phagocytic function was performed in 40 control, 73 RES-stimulated non-tumour-bearing and 59 tumour-bearing Wistar/FU rats in vivo. Tumour-bearing rats were inoculated with 10(6) x 1.0 cells of a syngeneic nitrosoguanidine-induced colonic carcinoma in the liver. Twenty-eight of these rats had been treated one day previously with Zymosan (3 mg x 100 g-1 i v) as a RES stimulant. The clearance/uptake rate (k) of Nanocoll was calculated from dynamic liver images by the slope in the plot 1n [1 - U(t)/U] versus t where t is time and U liver uptake. k-value in control animals was 0.45 +/- 0.01.10(-2) x s-1 Zymosan injection in non-tumour-bearing rats caused stati-stically significant higher clearance/uptake rate on day 1, through 8 after treatment compared to that of controls. On day 8 k-value was 0.64 +/- 0.04. In tumour-bearing rats the uptake rate (k) was on day 8 0.66 +/- 0.03, while in RES-stimulated tumour-bearing rats it was 0.64 +/- 0.03. Survival was 22 +/- 1 days in tumour bearing rats and 37 +/- 4 days in RES stimulated tumour-bearing rats. The average tumour volume after one week was 132 +/- 24 mm3 in non-stimulated rats and 20 +/- 5 mm3 in RES stimulated rats. There was a negative correlation between uptake rate and tumour volume and a positive correlation between uptake rate and survival on day 8 in non-stimulated tumour-bearing rats. Dynamic liver RES scintigraphy with small size 99Tcm albumin colloid (Nanocoll) can be used to measure RES phagocytic function and the effect of liver tumour growth on RES.

Adenocarcinoma↗

PubMedDate not supplied

Intratumoral distribution of microspheres.

Fifteen mu carbonized microspheres injected in two transplantable rat tumors, a hepatoma transplanted to the dorsum of one hindpaw and an adenocarcinoma transplanted into the liver, were found to be unevenly distributed and often in aggregates that seemed to fill intratumoral vessels. This finding can partly explain the increased vascular resistance in tumors after microsphere injection and makes the technique with repeated injections of microspheres disputable.

Animals↗

PubMedDate not supplied

Effects of local microwave hyperthermia and 5-fluorouracil in treatment of experimental liver cancer.

The effect of combined treatment with local hyperthermia and i.v. infusion of 5-fluorouracil was studied in 39 Wistar rats with a transplanted adenocarcinoma inoculated in the liver. Ten to 13 days later the rats were divided into three groups. Group A1 was subjected to local microwave hyperthermia (42 degrees C) for 1 h. During the hyperthermia, an i.v. infusion of 5-FU (20 mg/kg body weight) was given. In group A2 5-FU was administered under normothermic conditions. Group A3 received saline infusion under normothermic conditions. The mortality after infusion of 5-fluorouracil and hyperthermia increased during the first week after treatment. In group A1, a significant growth retardation of liver tumor was registered seven days after treatment. This effect was not superior to that of hyperthermia alone as previously described for the same experimental model. Studies of 5-FU pharmacokinetics in plasma were performed in another 20 Wistar rats. Ten rats were given an i.v. infusion of 5-FU during local hyperthermia, while the other 10 were infused under normothermic conditions. Plasma concentration of 5-FU was determined by isotachophoretic separation. The hyperthermia caused a faster decline in serum concentration of 5-FU, probably because of accelerated catabolism of the drug.

Adenocarcinoma↗

PubMedDate not supplied

A two-stage liver resection combined with longterm intraportal 5-FU infusion.

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Cecal Neoplasms↗

PubMedDate not supplied

The reliability of celiac angiography in diagnosing liver tumours.

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Alkaline Phosphatase↗

PubMedDate not supplied

Total body hyperthermia induced by a computerized microwave technique: studies in normal rats and in rats with liver tumors.

A computerized system for inducing total body hyperthermia by microwave irradiation was tested in rats. The tolerance to hyperthermia at different temperatures and fractions was studied as well as its effect on the growth of transplanted adenocarcinomas in the liver. Survival results indicated that 41.5 degrees C was maximum tolerated temperature both after single and repeated one hour exposures. Besides the high mortality with a greater temperature (42 degrees C) there was a significant rise in S-aspartate-amino-transferase (S-ASAT) and S-beta-hexosaminidase (beta-nagas) indicating damage of normal cells. No significant reduction of tumor volume could be registered after treatment with total body hyperthermia (41.5 degrees C) for one hour three times during a 24 hour period.

Adenocarcinoma↗

PubMedDate not supplied

Biochemical modulation of intraperitoneal fluorouracil by allopurinol-the effect on an experimental adenocarcinoma in the liver.

In a rat liver tumour system with a nitrosoguanidine-induced carcinoma and in an in vitro system with the same tumour, the effect of allopurinol on the toxicity and antitumour effect of 5-fluorouracil (5-FU) was explored. Two doses of 5-FU, 30 and 60 mg/kg b.w. intraperitoneally (i.p.), were tested with a large dose of allopurinol subcutaneously (s.c.( (300 mg) in rats. The drugs were given for three consecutive days. The lethal toxicity of 60 mg 5-FU i.p. could not be counteracted by allopurinol. Allopurinol and 30 mg 5-FU reduced the tumour growth rate more than 5-FU alone. The spleen was smaller, as a sign of increased toxicity, without allopurinol. The concentration of allopurinol and its metabolites in the general circulation was high. In vitro, there was no additive or specific effect of allopurinol. These results indicate some in vivo metabolic modulation of 5-FU efficacy by allopurinol if 5-FU is administered intraperitoneally and allopurinol systemically.

Adenocarcinoma↗