[Sinusoidal obstruction syndrome induced by monocrotaline in a large animal experiment - a pilot study]. / Sinusoidální obstrukcní syndrom indukovaný monokrotalinem v experimentu na velkém zvíreti - pilotní studie.

INTRODUCTION: Sinusoidal obstruction syndrome (SOS) is a disease which is caused by toxic injury to hepatic sinusoids. This syndrome is most frequently caused by myeloablative radiochemotherapy in patients before hematopoietic stem cells transplantation and also by oxaliplatin mainly in patients with colorectal liver metastases. The aim of this study was to establish a large animal model of SOS, which would enable further study of this disease and facilitate translation of experimental outcomes into human medicine. METHODS: A total of 27 domestic pigs (Prestice Black-Pied pig) were involved in this study (12 females). A group with a higher dose of monocrotaline (180 mg/kg) included 5 animals, and the remaining 22 pigs formed another group with a lower dose (36 mg/kg). Monocrotaline was administered via the portal vein and one week after the administration, partial hepatectomy of the left lateral liver lobe was performed. The animals were followed up for 3 weeks after monocrotaline administration. Regular ultrasound examinations were performed as well as examination of biochemical markers of liver and kidney functions and histological examination of liver parenchyma samples. RESULTS: The features of toxic liver injury which we observed in case of all animals were comparable with macroscopic and microscopic appearance of SOS. We recorded AST, ALT, bilirubin and ammonia elevation after monocrotaline administration. Echogenicity on ultrasound images of injured liver parenchyma was higher compared to echogenicity of healthy parenchyma. All the five animals from the first group with a higher monocrotaline dose had died before partial hepatectomy (1st-3rd day after monocrotaline administration). Death before partial hepatectomy occurred in 3 cases (6th and 7th day after monocrotaline administration) in the second group of 22 animals with a lower dose of monocrotaline. Death after partial hepatectomy occurred in 8 cases (7th-17th day after moncrotaline administration) in the same group. 11 animals survived the entire experimental period. The cause of death (in both groups) was metabolic failure in 10 animals and exsanguination in 4 animals, both due to severe hepatopathy. Death of 2 animals was not associated with monocrotaline intoxication (strangulation of small intestine, gastrectasis). CONCLUSIONS: We established a large animal model of SOS induced by monocrotaline administration (36 mg/kg via portal vein). This model can contribute to research of therapeutic modalities for this disease or to evaluation of surgical treatment of patients with SOS.Key words: sinusoidal obstruction syndrome monocrotaline oxaliplatin hepatotoxicity experimental model.

[Experimental processing of corrosion casts of large animal organs]. / Experimentální príprava korozivních preparátu orgánu velkého zvírete.

INTRODUCTION: Corrosion casts (CCs) are used for the visualization and assessment of hollow structures. CCs with filled capillaries enable (with the help of imaging methods) to obtain data for mathematical organ perfusion modelling. As the processing is more difficult in case of organs with greater volume of the vasculature, mainly organs from small animals have been cast up to now. The aim of this study was to optimize the protocol of corrosion casting of different organs of pig. Porcine organs are relatively easily accessible and frequently used in experimental medicine. METHOD: Organs from 10 healthy Prestice Black-Pied pigs (6 females, body weight 35-45 kg), were used in this study (liver, spleen, kidneys and small intestine). The organs were dissected, heparin was administered into the systemic circulation and then the vascular bed of the organs was flushed with heparinized saline either in situ (liver) or after their removal (spleen, kidney, small intestine). All handling was done under the water surface to prevent air embolization. The next step was an intraarterial (in case of the liver also intraportal) administration of Biodur E20® (Heidelberg, Germany) resin. After hardening of the resin the organ tissue was dissolved by 15% KOH and the specimen was rinsed with tap water. Voluminous casts were stored in 70% denatured alcohol, the smaller ones were lyophilized. The casts were assessed with a stereomicroscope, computed and microcomputed tomography (CT and microCT), a scanning electron microscope (SEM) and high-resolution digital microscope (HRDM). RESULTS: High-quality CCs of the porcine liver, kidneys, spleen and small intestine were created owing to the sophisticated organ harvesting, the suitable resin and casting procedure. Macroscopic clarity was improved thanks to the possibility of resin dying. Scanning by CT was performed and showed to be a suitable method for the liver cast examination. MicroCT, SEM and HRDM produced images of the most detailed structures of vascular bed. Despite the fact that SEM seems to be an irreplaceable method for CCs quality control, it seems that this modality could be partly replaced by HRDM. MicroCT enabled to obtain data about three-dimensional layout of the vascular bed and data for mathematical modelling of organ perfusion. With regard to the quality of the CCs, they could also be used to teach human anatomy. CONCLUSIONS: The protocol of the corrosion casting of the porcine liver, kidneys, spleen and small intestine CCs was optimized. Thanks to different imaging methods, the CCs can be used as a source of data on three-dimensional architecture of the vascular bed. These data can be used for mathematical modeling of organ perfusion which can be helpful for example for optimization of organ resections.Key words: corrosion casts microvasculature Biodur E20® domestic pig animal model.

[Liver metastases from colon and rectal cancer in terms of differences in their clinical parameters]. / Jaterní metastázy karcinomu kolon a rekta z pohledu rozdílu v klinických parametrech.

INTRODUCTION: From the clinical point of view, rectal cancer and colon cancer are clearly different nosological units in their progress and treatment. The aim of this study was to analyse and clarify the differences between the behaviour of liver metastases from colon and rectal cancer. The study of these factors is important for determining an accurate prognosis and indication of the most effective surgical therapy and oncologic treatment of colon and rectal cancer as a systemic disease. METHOD: 223 patients with metastatic disease of colorectal carcinoma operated at the Department of Surgery, University Hospital in Pilsen between January 1, 2006 and January 31, 2012 were included in our study. The group of patients comprised 145 men (65%) and 117 women (35%). 275 operations were performed. Resection was done in 177 patients and radiofrequency ablation (RFA) in the total of 98 cases. Our sample was divided into 3 categories according to the location of the primary tumor to C (colon), comprising 58 patients, S (c. sigmoideum) in 61 patients, and R (rectum), comprising 101 patients. Significance analysis of the studied factors (age, gender, staging [TNM classification], grading, presence of mucinous carcinoma, type of operation) was performed using ANOVA test. Overall survival (OS), disease-free interval (DFI) or no evidence of disease (NED) were estimated using Kaplan-Meier curves, which were compared with the log-rank and Wilcoxon tests. RESULTS: As regards the comparison of primary origin of colorectal metastases in liver regardless of their treatment (resection and RFA), our study indicated that rectal liver metastases showed a significantly earlier recurrence than colon liver metastases (shorter NED/DFI). Among other factors, a locally advanced finding, further R2 resection of liver metastases and positivity of lymph node metastases were statistically significant for the prognosis of an early recurrence of the primary colon and sigmoid tumor. Furthermore, we proved that in patients with primary rectal carcinoma, DFI (after the resection of liver metastases) was not influenced by the positivity of lymph node metastases of primary tumor or locally advanced primary tumor. The other factors studied (time from diagnosis of organ metastases to primary operation, grading, sex or age) were not shown to be statistically significant for the prognosis of OS and DFI (colorectal cancer in total). CONCLUSION: As proven by our study, rectal cancer and colon cancer are two different nosological units with specific prognostic factors with respect to their liver metastases. These differences have not been fully understood yet and require further exploration and classification based not only on histopathological, immunohistochemical and clinical factors, but also on molecular biological parameters. KEY WORDS: colon carcinoma metastases rectal carcinoma metastases prognostic factors overall survival - liver metastases.