Probiotics partly reverse increased bacterial translocation after simultaneous liver resection and colonic anastomosis in rats.

Background and aims
Tertiary peritonitis is a severe persisting intra-abdominal infection and associated with high mortality. The aim was to find significant risk factors for mortality and tertiary peritonitis including the Mannheim Peritonitis Index (MPI), the Acute Physiology and Chronic Health Evaluation (APACHE) II score, and a sumscore of both.

Age, microbiology and prognostic scores help to differentiate between secondary and tertiary peritonitis

https://www.surgical.theclinics.com/article/S0039-6109(03)00233-0/pdf

Isolated hepatic perfusion: experimental evidence and clinical utility.

Hyperthermic antiblastic isolated hepatic perfusion (IHP) with melphalan has been recently proposed as an alternative therapeutic option for patients with unresectable liver tumors. Although melphalan–heat antiblastic synergism is at a maximum at temperatures higher than 41 °C, IHP has so far been performed in humans at lower temperatures. In this experimental work, we compared IHP under mild versus true hyperthermic conditions in terms of drug pharmacokinetics and liver function. Ten pigs were submitted to IHP with melphalan 1.5 mg/kg at a mean temperature of 40 °C (group A, n = 5) or 42 °C (group B, n = 5). After a 60-minute perfusion, a 15-minute washout was performed. Perfusate-to-plasma leakage was monitored using scintigraphy. Throughout perfusion, samples from the systemic blood, perfusate, and liver parenchyma were obtained to measure melphalan concentrations. Liver function was assessed using standard blood tests and the indocyanine green-based test. No deaths related to the IHP procedure were recorded. All animals had transient liver function impairment, with all liver function test results returning to normal within the observation period. At histologic examination, liver damage was similar under both hyperthermic conditions. Melphalan levels in the perfusate were not significantly different in the two study groups (the mean perfusate/plasma area under the curve from 0 to 60 minutes ratios were 463 and 501, respectively). These results correlated well with those obtained using the scintigraphic method. Liver drug concentrations remained unchanged after true hyperthermia IHP. Under true hyperthermic conditions, neither an increase in liver parenchyma toxicity nor changes in melphalan pharmacokinetics were observed. These findings support the use of true hyperthermia in the clinical setting to exploit fully the antitumor synergism between melphalan and heat.

True versus Mild Hyperthermia during Isolated Hepatic Perfusion: Effects on Melphalan Pharmacokinetics and Liver Function

Isolated hyperthermic perfusion of the liver was performed for 45 min in 27 pigs via hepatic artery and portal vein at mean inflow temperatures between 40.7 and 41.2°C. In two study groups B and C (n = 9 pigs each) 50 μg recombinant human tumor necrosis factor-α (rhTNFα) per kg body weight were added to the perfusate, whereas in a control group A liver perfusion was done without rhTNFα. Before reperfusion the livers were washed out with Ringer’s solution in all groups followed by a protein solution in group C. At 30 and 60 min after reperfusion the maximum systemic rhTNFα concentrations were significantly higher in group B with 68 and 61 ng/ml compared to 14.5 and 14.9 ng/ml in group C (p

Isolated hyperthermic liver perfusion with high dose tumor necrosis factor alpha in pigs: an experimental study in preparation of clinical Use.

Our study was aimed at developing a reliable method of hyperthermic isolated liver perfusion (HILP) in pigs and at assessing its local and systemic side effects. HILP was performed via the hepatic artery and portal vein in 15 animals. The perfusate consisted of blood (200 ml), oxypolygelatine (500 ml), Ringer's solution (1000 ml), and trapped intrahepatic blood. HILP was carried out for 45 min at a mean perfusate inflow temperature of 41.2 degrees C. The mean portal flow and pressure were adjusted to 500 ml/min and 20-25 mm Hg; the mean arterial flow and pressure were 130 ml/min and 40-60 mm Hg, respectively. After 20 min of perfusion the mean temperature in the right and the left liver lobe were 40.8 degrees C and 40.3 degrees C and remained almost constant over the whole perfusion period. Liver enzymes (alanine aminotransferase and aspartate aminotransferase) and serum lactate levels showed slight increases after perfusion but normalized within 1 week. Histology of liver parenchyma showed only mild pathological changes, which were also reversible within 7 days. The presented method of HILP is a safe and reproducible technique for isolated hyperthermic liver perfusion. Based on this animal model, experimental HILP with different chemotherapeutic agents can be investigated in order to assess hepatic and systemic toxicity of this therapy.

A Porcine Model for Investigation of Hyperthermic Isolated Liver Perfusion

Asanguineous hyperthermic liver perfusion was performed in five and seven pigs for 30 and 45 min respectively. Laboratory data, including changes of liver enzyme levels and results of liver function tests, as well as morphological alterations of liver structure, were compared with data from a 45-min oxygenated hyperthermic liver perfusion. In the groups undergoing asanguineous liver perfusion survival was four of five and five of seven animals. In the oxygenated group six of seven pigs survived. Liver enzymes and function tests in the two groups with a 45-min perfusion time were not significantly different. All enzyme and laboratory test values returned to normal within 1 week. Similarly morphological changes were reversible within 1 week. The results suggest that asanguineous isolated hyperthermic liver perfusion up to 45 min is feasible without damage to liver tissue.

Asanguineous Isolated Hyperthermic Perfusion of the Liver: Results of an Experimental Study in Pigs

Die potentiell zytotoxische Wirkung von Tumornekrosefaktor alpha (TNFα) ist aus In vitro- und In vivo-Versuchen bekannt, wobei milde Hyperthermie einen synergistisch antineoplastischen Effekt bewirkt [1]. Die Gabe von TNF geht jedoch aufgrund von Mediatorfreisetzung mit erheblichen systemischen Nebenwirkungen einher [2, 3]. Fur eine effektive zytostatische Therapie sind Dosierungen von etwa 50 µgTNFα/kgKG erforderlich. Da die MTD (max. tolerierte Dosis) beim Menschen bei nur ca. 5 μgTNFα/kgKG liegt, kann eine effektive Tumortherapie mit TNFα lediglich als isolierte Organperfusion durchgefuhrt werden. Klinisch ist dies bei der isolierten Extremitatenperfusion zur Behandlung von irresektablen Weichteiltumoren bereits etabliert [4]. Entsprechende Daten uber eine isolierte Leberperfusion mit hochdosierter TNF-Gabe liegen bislang noch nicht vor. In einer tierexperimentellen Studie wurden daher funktionelle, pharmakologische und morphologische Untersuchungen zur isolierten hyperthermen Leberperfusion mit rekombinantem humanem TNFα (rhTNFα) vorgenommen.

Tierexperimentelle Untersuchungen zur isolierten Leberperfusion mit Tumornekrosefaktor α

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Papers

Isolated hyperthermic liver perfusion with high dose tumor necrosis factor alpha in pigs: an experimental study in preparation of clinical Use.

A Porcine Model for Investigation of Hyperthermic Isolated Liver Perfusion

Asanguineous Isolated Hyperthermic Perfusion of the Liver: Results of an Experimental Study in Pigs

Tierexperimentelle Untersuchungen zur isolierten Leberperfusion mit Tumornekrosefaktor α