Radiofrequency ablation of colorectal liver metastases.

INTRODUCTION: Radical liver resection is the only method for the treatment of patients with colorectal liver metastases (CLM); however, only 20-30% of patients with CLMs can be radically treated. Radiofrequency ablation (RFA) is one of the possible methods of palliative treatment in such patients. METHODS: RFA was performed in 381 patients with CLMs between 01 Jan 2001 and 31 Dec 2018. The mean age of the patients was 65.2±8.7 years. The male to female ratio was 2:1. Open laparotomy was done in 238 (62.5%) patients and the CT-navigated transcutaneous approach was used in 143 (37.5%) patients. CLMs.

Growth of colorectal liver metastases is not accelerated by intraportal administration of stem cells after portal vein embolization.

INTRODUCTION: Future liver remnant volume (FLRV) is a crucial factor impacting resectability of colorectal liver metastases (CLM). In case of low FLRV, augmentation can be done by performing portal vein embolization (PVE). However, there is a risk of progression of CLM between PVE and resection. Intraportal application of autologous hematopoietic stem cells (HSC) is a possibility to accelerate the growth of FLRV. The effect of thus applied SC on CLM progression still remains unclear, though. METHODS: 63 patients underwent PVE between 2003 and 2015. In 20 patients a product with HSC was applied intraportally on the first day after PVE (PVE HSC group). HSC were gained from peripheral blood (10 patients) or bone marrow (10 patients). FLRV and volume of liver metastases (VLM) were evaluated by CT volumetry. The gained data were statistically evaluated in relation to the disease free interval (DFI), overall survival (OS), achievement of CLM resectability and progression of extrahepatic metastases. We compared the PVE HSC group with the group of patient undergoing simple PVE. RESULTS: No significant difference in FLRV and VLM growth was observed between the study groups. The percentage of exploratory laparotomies was smaller in the group with PVE and HSC application. Patients with simple PVE had a significantly higher incidence of extrahepatic metastases during follow up. We did not observe any significant differences in DFI and OS between the groups. CONCLUSION: HSC application did not accelerate CLM growth in comparison with PVE alone. PVE and HSC application had a higher percentage of patients undergoing liver resection and a lower incidence of extrahepatic metastases.

[Experimental promotion of liver regeneration after portal vein branch ligation]. / Moznosti experimentálního ovlivnení regenerace jaterního parenchymu v souvislosti s ligací vetví portální zíly.

INTRODUCTION: Portal vein embolization or ligation (PVE/PVL) is part of most multi-stage liver procedures in the case of low future liver remnant volume (FLRV). PVE initiates compensatory hypertrophy of non-occluded liver parenchyma. This hypertrophy is stimulated by an increased volume of portal blood in the non-occluded veins. PVE results in adequate FLRV growth necessary for resection only in 63-96% patients. The aim of this publication is to summarize the possibilities of influencing liver regeneration after PVE/PVL in an experiment using cytokines (TNF-α, IL-6), a monoclonal antibody against TGF-ß1 (MAB TGF-ß1) and mesenchymal stem cells (MSC). METHODS: The experimental model of PVE/PVL was chosen as best compatible for potential use in human medicine. 9 (control group), 9 (TNF-α group), 8 (IL-6 group), 6 (MSC group) and 7 piglets (MAB TGF-ß1 group) were enrolled in individual studies. We performed laparotomy with PVL of the right-sided liver lobes under general anaesthesia. The following amounts of substances were applied in the non-occluded portal vein branches immediately after PVL: physiological solution (control group), recombinant porcine TNF-α (5 µg/kg), recombinant porcine IL-6 (0.5 µg/kg) and MSC (8.75, 14.0, 17.0, 17.5, 43.0 and 61.0 x 106 MSC). MAB TGF-ß1 was applied 24 hours after PVL (40 µg/kg). Biochemical parameters were analysed repeatedly and FLRV ultrasound assessments were performed in the postoperative period. The experiments were ended on postoperative day 14 by sacryfiing the animals under general anaesthesia. Liver samples of hypertrophic and atrophic liver parenchyma were analysed. RESULTS: Repeated ultrasound assessments of the effects of MSC, TNF-α, IL-6 and MAB TGF-ß1 compared with the physiological solution in the control group demonstrated statistically significant acceleration of FLRV growth in the experimental groups. For MSC, maximum growth was observed between postoperative days 3 and 7, on day 7 for TNF-α, between days 3 and 7 for MAB TGF-ß1 and on day 7 for IL-6. Serum levels of AST and ALT increased after PVL and MSC whereas other biochemical parameters showed no statistically significant differences. We identified individual MSC using immunohistochemistry in the hypertrophic tissue of the MSC group. A statistically significant difference was observed in the number of binucleated hepatocytes, with their increased concentration in the IL-6 group. CONCLUSION: Application of IL-6, TNF-α, MAB TGF-ß1 and MSC seems to provide suitable stimulation for achieving faster FLRV growth. Nevertheless, many controversial questions still remain to be answered with respect to the mechanism of their respective effects.Key words: liver regeneration portal vein embolization large animal experiment mesenchymal stem cells cytokines.

[Liver hemangiomas - when is invasive treatment indicated?] / Hemangiomy jater - kdy indikovat invazivní lécbu?

INTRODUCTION: Liver hemangiomas are the most common benign tumors of the liver. Most are asymptomatic and are found accidentally by ultrasonography, computed tomography or magnetic resonance imaging of the abdomen. Liver hemangiomas usually do not need any treatment. Nevertheless, symptomatic, giant hemangiomas can be indicated for surgery, embolization or thermoablation. The aim of this study was to define based on our own experience and on the literature when and what treatment option should be indicated in patients suffering from liver hemangioma. METHOD: In the last five years 37 patients with giant hemangiomas indicated for invasive treatment were enrolled in the study. The mean size of the hemangiomas was 67 mm (45-221 mm). Multiple hemangiomas were present in 11 (29.7%) patients. Enucleation was performed in 15 (40.5%), non-anatomical liver resection in three, (8.1%), left lobectomy in one (2.7%) and exploratory laparotomy for a suspected malignant liver tumor in two (5.4%) patients where malignancy was excluded based on contrast enhanced peroperative ultrasonography. Percutaneous transarterial embolization (TAE) was performed in 16 (43.2%) patients. RESULTS: There was zero mortality. A hematoma in the resection line, with spontaneous regression was present in two (10.5%) patients after the surgery. The post-embolization syndrome was presented in three (16.7%) patients after TAE. Progression of the hemangioma was seen in three (28.8%), regression in six (37.5%) patients, and in seven (43.8%) patients the finding remained stable in the interval of 14 years after TAE. CONCLUSION: Conservative approach is can be applied in most liver hemangiomas, especially in small, asymptomatic lesions. Liver surgery is indicated in giant symptomatic or growing hemangiomas with the diameter over 10 cm or in non-specific lesions where the preoperative diagnosis is uncertain. We recommend enucleation as the method of choice, or non-anatomic liver resection. TAE is indicated in high-risk patients and can be repeated if the hemangioma progresses. The use of other methods such as radiofrequency ablation needs to be verified in large clinical studies.Key words: liver hemangiomas - treatment methods.

[Liver metastases of malignant melanoma - utility of resection or radiofrequency ablation]. / Jaterní metastázy maligního melanomu - mají resekce nebo radiofrekvencní ablace smysl?

INTRODUCTION: Incidence of cutaneous and uveal forms of malignant melanoma (MM) has increased significantly in the population in the last years. Biological behavior of both these forms of MM is different and is associated with the development of liver metastases. The prognosis of patients with MM liver metastases is generally poor. The authors seek to consider the sense and the possibilities of surgical treatment of MM liver metastases. METHOD: Seven patients with liver metastases of MM were operated on in the Hepatobiliary Center of the Department of Surgery, University Hospital in Pilsen during the last ten years. Four patients suffered from the uveal and three from the cutaneous form of MM. Mean age of the patients was 58.8 years. R0 liver resection was performed in 3, and radiofrequency ablation in 1 patient. In the remaining 3 patients the operation finished by exploratory laparotomy due to tumor progression. RESULTS: Two patients died in the interval of 6 and 25 months after liver surgery for tumor dissemination. Two patients continue to show disease free survival, currently of 22 and 28 months. CONCLUSION: Liver metastases of MM have a very poor prognosis. Surgical treatment indicated by the multidisciplinary team provides, together with further multimodal treatment, a chance for long-term survival and its indication is justified in selected patients.Key words: malignant melanoma - liver metastases - surgical treatment.

Molecular profile of 5-fluorouracil pathway genes in colorectal carcinoma.

BACKGROUND: This study addresses involvement of major 5-fluorouracil (5-FU) pathway genes in the prognosis of colorectal carcinoma patients. METHODS: Testing set and two validation sets comprising paired tumor and adjacent mucosa tissue samples from 151 patients were used for transcript profiling of 15 5-FU pathway genes by quantitative real-time PCR and DNA methylation profiling by high resolution melting analysis. Intratumoral molecular profiles were correlated with clinical data of patients. Protein levels of two most relevant candidate markers were assessed by immunoblotting. RESULTS: Downregulation of DPYD and upregulation of PPAT, UMPS, RRM2, and SLC29A1 transcripts were found in tumors compared to adjacent mucosa in testing and validation sets of patients. Low RRM2 transcript level significantly associated with poor response to the first-line palliative 5-FU-based chemotherapy in the testing set and with poor disease-free interval of patients in the validation set irrespective of 5-FU treatment. UPP2 was strongly methylated while its transcript absent in both tumors and adjacent mucosa. DPYS methylation level was significantly higher in tumor tissues compared to adjacent mucosa samples. Low intratumoral level of UPB1 methylation was prognostic for poor disease-free interval of the patients (P = 0.0002). The rest of the studied 5-FU genes were not methylated in tumors or adjacent mucosa. CONCLUSIONS: The observed overexpression of several 5-FU activating genes and DPYD downregulation deduce that chemotherapy naïve colorectal tumors share favorable gene expression profile for 5-FU therapy. Low RRM2 transcript and UPB1 methylation levels present separate poor prognosis factors for colorectal carcinoma patients and should be further investigated.

Protein expression of ATP-binding cassette transporters ABCC10 and ABCC11 associates with survival of colorectal cancer patients.

PURPOSE: This study investigated the prognostic importance of protein expression of ATP-binding cassette (ABC) transporters ABCC10 and ABCC11 in colorectal cancer. METHODS: Protein content of ABCC10 and ABCC11 was assessed in tumor tissue blocks of 140 colorectal cancer patients and associated with survival of patients with regard to 5-fluorouracil-based therapy. RESULTS: Low ABCC10 protein content in tumors increased hazard ratio of patient's death more than three times in comparison with high ABCC10-expressing tumors (P = 0.004). In contrast, the low ABCC11 content increased the hazard ratio of cancer recurrence in patients almost four times (P = 0.016). Analysis of patients treated with regimens based on 5-fluorouracil revealed that patients with low ABCC11 content in their tumors had shorter disease-free interval than those with higher content (P = 0.024). CONCLUSIONS: The present study shows for the first time that the protein expression of ABCC10 significantly associates with overall survival and the expression of ABCC11 with disease-free interval of colorectal cancer patients and provides strong impulse for further validation of their prognostic value in colorectal cancer.

[Comparison of percutaneous and open approach to radiofrequency ablation of colorectal liver metastases in Teaching Hospital Pilsen in 20012015]. / Porovnání perkutánní a otevrené radiofrekvencní ablace metastáz kolorektálního karcinomu ve FN Plzen v letech 20012015.

INTRODUCTION: Radiofrequency ablation (RFA) is a well-established method for palliative therapy of unresectable liver tumors. We use an open or percutaneous approach for the treatment of colorectal liver metastases (CLM). METHOD: Clinical data of patients undergoing percutaneous or open RFA for CLM between January 2001 and January 2015 were included in the retrospective study. We evaluated clinical factors for overall survival (OS), no evidence of disease (NED) and non-ablation in relation to tumor sizes and numbers, type of approach and type of used probes. RESULTS: 147 patients underwent RFA for CLM in this time period. Mean age was 65 years. 168 RFAs were performed in total. OS was influenced by a high number of censors. OS for the first and third years was 93.6% and 61% with no statistical differences between the percutaneous and open approach. NED was significantly shorter in patients with the percutaneous approach. NED was not influenced neither by size nor number of the lesions. A higher risk of non-ablation was observed as statistically significant in patients with percutaneous RFA. A higher, although not statistically significant, risk of non-ablation was also observed for larger metastases. Patients with percutaneous RFA showed a shorter stay in the hospital and fewer complications. CONCLUSION: RFA is an alternative approach to the treatment of unresectable CLM. In our study the open approach was associated with a lower risk of non-ablation. Percutaneous RFA showed a lower risk of complications and a shorter stay in the hospital. KEY WORDS: radiofrequency ablation percutaneous RFA colorectal liver metastases CLM palliative therapy.

[Extragenital malignant Müllerian carcinosarcoma with invasion of inferior vena cava - a case report]. / Extragenitální maligní Müllerianský karcinosarkom infiltrující dolní dutou zílu - kazuistika.

UNLABELLED: The authors present the case of a 57-year-old woman with a very rare extragenital malignant retroperitoneal Müllerian carcinosarcoma invading the inferior vena cava. Tumor resection with partial resection of the vena cava wall and resection of metastases in the pelvic area is described. The authors further discuss diagnostic options of metastases of this tumour and the recommended adjuvant chemotherapy. KEY WORDS: extragenital Müllerian carcinosarcoma malignant mixed Müllerian tumour - diagnosis therapy.

[Granulomatous inflammation in differential diagnosis of hepatobiliary malignancy]. / Granulomatózní zánety v diferenciální diagnostice malignit hepatobiliárního traktu - kazuistiky.

UNLABELLED: The authors present two case reports to demonstrate wide differential diagnosis of granulomatous disorders of the hepatobiliary tract. Isolated granulomatous disorders are very rare in this area. Differantial diagnosis includes infectious and systemic diseases or chemical irritation. Granulomas often immitate malignant tumors and the surgeon could be first to diagnose this disease during liver resection or cholecystectomy. KEY WORDS: granulomatous inflammation hepatic granuloma non-specific inflammation liver resection cholecystectomy.

Porcine liver vascular bed in Biodur E20 corrosion casts.

BACKGROUND: Pigs are frequently used as animal models in experimental medicine. To identify processes of vascular development or regression, vascular elements must be recognised and quantified in a three-dimensional (3D) arrangement. Vascular corrosion casts enable the creation of 3D replicas of vascular trees. The aim of our study was to identify suitable casting media and optimise the protocol for porcine liver vascular corrosion casting. MATERIALS AND METHODS: Mercox II® (Ladd Research, Williston, Vermont, USA) and Biodur E20® Plus (Biodur Products, Heidelberg, Germany) were tested in 4 porcine livers. The resins (volume approximately 700 mL) were injected via the portal vein. Corrosion casts were examined by macro-computed tomography, micro-computed tomography and scanning electron microscopy. RESULTS: For hepatectomies, the operating protocol was optimised to avoid gas or blood clot embolisation. We present a protocol for porcine liver vascular bed casting based on corrosion specimens prepared using Biodur E20® epoxy resin. CONCLUSIONS: Only Biodur E20®Plus appeared to be suitable for high-volume vascular corrosion casting due to its optimal permeability, sufficient processing time and minimum fragility. Biodur E20® Plus is slightly elastic, radio-opaque and alcohol-resistant. These properties make this acrylic resin suitable for not only vascular research but also teaching purposes.

[Chemoembolization with Drug Eluting Beads (TACE DEB) in patients with primary unresectable hepatocellular carcinoma (HCC)]. / Transarteriální chemoembolizace pomocí "drug eluting beads" (TACE DEB) u nemocných s radikálne neodstranitelným hepatocelulárním karcinomem (HCC).

INTRODUCTION: The incidence of HCC is growing all over the word. Liver resection and transplantation are the methods of choice in only 25% of patients, representing radical treatment approaches. TACE is a method of palliative treatment in patients with primary unresectable disease. MATERIAL AND METHODS: 35 patients (27 men and 8 women) of an average age of 73.4 ± 7.2 years with HCC of average cumulative diameter 83.8 ± 36.3 mm were treated by TACE DEB with Doxorubicin. Solitary and multiple lesions were presented in 28 and 7 patients, respectively. 31 patients were classified as Child A, and 4 as Child B. One year overall survival, disease-specific, disease-free interval and their correlation with patients age, gender, as well as the number and cumulative diameter of tumours and complications after procedure were evaluated. RESULTS: 30-day mortality and morbidity rate was 0 and 8.6%, respectively. The so-called postembolization syndrome developed in 25.7% of patients. Repeated TACE was performed in 14 (40%) patients due to tumour progression. In two patients (5.7%) we performed liver resection after TACE. According to the RECIST criteria there was no complete response, partial response was presented in 17.1, stable disease in 37.1 and progression of disease in 25.7% of patients. One year overall survival, tumour-specific survival and disease-free survival was 69.7%, 88.9 and 49.3%, respectively. Better overall survival (p < 0.02) was achieved in patients < 75 years old. Worse disease-free interval was observed in patients with complication after TACE (p < 0.01). No significant differences were found in the other evaluated parameters. CONCLUSION: TACE is the method of palliative treatment in patients with unresectable HCC. There is no progression of HCC in one-half of patients after TACE. Better results are achieved in younger patients and in patients with no complications of procedure.

Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome.

Commensal bacteria in the colon may play a role in colorectal cancer (CRC) development. Recent studies from North America showed that Fusobacterium nucleatum (Fn) infection is over-represented in disease tissue versus matched normal tissue in CRC patients. Using quantitative real-time polymerase chain reaction (qPCR) of DNA extracted from colorectal tissue biopsies and surgical resections of three European cohorts totalling 122 CRC patients, we found an over-abundance of Fn in cancerous compared to matched normal tissue (p < 0.0001). To determine whether Fn infection is an early event in CRC development, we assayed Fn in colorectal adenoma (CRA) tissue from 52 Irish patients. While for all CRAs the Fn level was not statistically significantly higher in disease versus normal tissue (p = 0.06), it was significantly higher for high-grade dysplasia (p = 0.015). As a secondary objective, we determined that CRC patients with low Fn levels had a significantly longer overall survival time than patients with moderate and high levels of the bacterium (p = 0.008). The investigation of Fn as a potential non-invasive biomarker for CRC screening showed that, while Fn was more abundant in stool samples from CRC patients compared to adenomas or controls, the levels in stool did not correlate with cancer or adenoma tissue levels from the same individuals. This is the first study examining Fn in the colonic tissue and stool of European CRC and CRA patients, and suggests Fn as a novel risk factor for disease progression from adenoma to cancer, possibly affecting patient survival outcomes. Our results highlight the potential of Fn detection as a diagnostic and prognostic determinant in CRC patients.

[Liver and pulmonary metastases of the colorectal carcinoma - the experience of the Department of Surgery, University Hospital in Pilsen]. / Jaterní a plicní metastázy kolorektálního karcinomu - zkusenosti Chirurgické kliniky FN v Plzni.

INTRODUCTION: Liver and pulmonary metastases of the colorectal carcinoma develop in about 20-70%, resp. in 10-22% patients with the colorectal carcinoma. Their treatment is still a matter of discussion. The aim of our study was to evaluate the results of surgical treatment as a part of the multimodal approach. MATERIAL AND METHODS: 30 patients with liver and pulmonary colorectal metastases were operated on between 2002 and 4/2013. The average age was 62.8 ± 10.7 years. 19 patients had metachronous and 11 synchronous metastases. The liver metastases preceded pulmonary in 14 cases, and vice versa in 5 patients. Both types of metastases developed in seven patients simultaneously. Liver resection was performed in 23, radiofrequency ablation (RFA) in 7 patients. Laser pulmonary metastasectomy was performed in 15, pulmonary resection in 14 and RFA in one patient. The liver procedure preceded pulmonary in 25 patients. 73.3% patients had adjuvant oncological treatment. RESULTS: 30 days mortality rate was 3.3% (N=1) for the actinomycotic sepsis complicated with MRSA infection. Morbidity rate was 10%. Recurrence of liver metastases developed in 6 patients. RFA was performed in all patients. The median of overall and disease free survival was 6.9, resp. 1.1 years. CONCLUSION: Surgical treatment as a part of the multimodal treatment is the only radical treatment for patients with liver and pulmonary metastases. It offers good long-term results.

[Prognostic clinical factors in colorectal cancer after radical therapy]. / Klinické prognostické faktory kolorektálního karcinomu po jeho radikální lécbe.

INTRODUCTION: Colorectal anastomoses frequently become the site of of complications after surgical procedures for colorectal cancer. Anastomotic dehiscence has a significant impact on the whole p postoperative disease course, may influence the overal survival (OS) and disease free interval (DFI). The aim of our study was to analyze clinical and histopathological factors, that could facilitate detection of dehiscences and are related to the prognosis of patients. MATERIAL AND METHODS: The authors performed statistical analysis of a cohort of patients (340 pacients, 207 males, 133 females) who underwent radical resection followed by anastomosis on the large intestine during 2003-2007. The following factors were assessed: age, gender, staging, protective stoma, neoadjuvant chemotherapy, neoadjuvant radiotherapy, adjuvant chemotherapy, adjuvant radiotherapy and anastomotic insufficiency. Complications were evaluated according to Clavien and Dindo classification. RESULTS: The analysis confirmed the following factors to be statistically significant for prognosis of OS and DFI: In stage T4 subjects, the risk of death was 2.5 x higher and the risk of recurrence was 1.9 x higher than in the lower disease stage subjects. The presence of N2 lymph node metastases increases the risk of death 3.7 x and the risk of recurrence 3.6 x, compared to N0 and N1 cases. The presence of postoperative complications classified asf III.-V. grade according to Clavien and Dindo classification increases the risk of death 4x. The risk of death was 5.5 x higher in patients with dehiscence of anastomosis. The surprising finding was that even protective stoma increases the risk of death 5.4 x. Patients who did not undergo adjuvant chemotherapy were at 2 x higher risk of death. In patients with IIIA, IIIB, IV, V complications, the following factors proved to be statistically significant for prognosis of OS: leakage, protective stoma, adjuvant chemotherapy and adjuvant oncological treatment. In patients with complications I and II, the following factors were proved to be statistically significant for prognosis of OS: staging and lymph nodes metastases. Multivariate analysis CART confirmed significant correlation between the lymph nodes positivity and the Clavien and Dindo classification of complications. CONCLUSION: Analysis of clinical and histopathological factors is important for prediction of prognosis in patients with colorectal cancer after radical surgical treatment. Detection and application of these prognostic factors in postoperative period could influence the strategy of treatment and thus the overal survival in patients with radical resections for colorectal carcinoma. Nonadministration of adjutant chemotherapy results in a significant decrease in OS and DFI.

Immediately preoperative use of biological therapy does not influence liver regeneration after large resection--porcine experimental model with monoclonal antibody against epidermal growth factor.

BACKGROUND: The aim of this work was to study the influence of isolated biological therapy administered immediately before extended liver resection on liver function and regenerative capacity of future liver remnant (FLR) in a large-animal experiment. MATERIALS AND METHODS: Nineteen piglets were included in this study (10 in the control group and 9 in the experimental group). A port-a-cath was introduced into the superior caval vein. On days 11 and 4 before liver resection, cetuximab was administered via this port at 400 mg/m2 of piglet body surface. Physiological solution was applied to the control group. Resection of the left lateral, left medial and right medial hepatic lobes was followingly performed (reduction of 50-60% of liver parenchyma). Blood samples were collected at different times before the operation and after liver resection. Serum levels of bilirubin, urea, creatinine, alkaline phosphatase, gamma glutamyltransferase, cholinesterase, aspartate aminotransferase, alanine aminotransferase, albumin, C-reactive protein and transforming growth factor-ß1 were assessed. The ultrasonographic examinations at different time points were performed pre-operatively and after liver resection in order to assess the liver volume. The biopsies from the liver parenchyma were examined for proliferative activity, binocluated hepatocytes, size of hepatocytes, and the length of the lobuli. The comparison of distribution of the studied parameters between the groups was carried out using the Wilcoxon test. The Spearman rank correlation co-efficient was used because of the non-Gaussian distribution of the parameter values. The whole development of the studied parameters over time was compared between the groups using ANOVA. RESULTS: There were no important complications of administration of biologic therapy during the operation or throughout the peri-operative period. There was no statistically significant difference in the regeneration of FLR nor were any differences in biochemical, immunoanalytical and histological parameters detected. CONCLUSION: The achieved results of comparable liver regeneration in both the experimental and control groups confirms the use of biological treatment with cetuximab in the pre-operative period for minimizing the recovery period.

The role of ABC transporters in progression and clinical outcome of colorectal cancer.

Worldwide, colorectal cancer (CRC) is the third most common cancer, with the highest mortality rates occurring in Central Europe. The use of chemotherapy to treat CRC is limited by the inter-individual variability in drug response and the development of cancer cell resistance. ATP-binding cassette (ABC) transporters play a crucial role in the development of resistance by the efflux of anticancer agents outside of cancer cells. The aim of this study was to explore transcript levels of all human ABCs in tumours and non-neoplastic control tissues from CRC patients collected before the first line of treatment by 5-fluorouracil (5-FU)-containing regimen. The prognostic potential of ABCs was evaluated by the correlation of transcript levels with clinical factors. Relations between transcript levels of ABCs in tumours and chemotherapy efficacy were also addressed. The transcript profile of all known human ABCs was assessed using real-time polymerase chain reaction with a relative standard curve. The majority of the studied ABCs were down-regulated or unchanged between tumours and control tissues. ABCA12, ABCA13, ABCB6, ABCC1, ABCC2 and ABCE1 were up-regulated in tumours versus control tissues. Transcript levels of ABCA12, ABCC7 and ABCC8 increased in direction from colon to rectum. Additionally, transcript levels of ABCB9, ABCB11, ABCG5 and ABCG8 followed the reverse significant trend, i.e. a decrease in direction from colon to rectum. The transcript level of ABCC10 in tumours correlated with the grade (P = 0.01). Transcript levels of ABCC6, ABCC11, ABCF1 and ABCF2 were significantly lower in non-responders to palliative chemotherapy in comparison with responders. The disease-free interval of patients treated by adjuvant chemotherapy was significantly shorter in patients with low transcript levels of ABCA7, ABCA13, ABCB4, ABCC11 and ABCD4. In conclusion, ABCC11 may be a promising candidate marker for a validation study on 5-FU therapy outcome.

[Liver metastases of other than colorectal origin]. / Jaterní metastázy jiného nez kolorektálního puvodu.

AIM: Colorectal carcinoma is the commonest malignancy with liver metastases. Approximately 25-30% of these metastases are resectable with good long-term outcomes. Liver metastases of so called non-colorectal carcinomas are significantly less common, and considering different biological character of these metastases, compared to colorectal ones, surgical management of some of these types is debatable, however, in some cases remains highly successful. The aim of this study was to assess the authors' outcomes of surgical and termoablation therapy of non-colorectal liver metastases. METHODS: The authors present their experience with surgical treatment in 68 patients - mean age of 58.2 y.o.a (33.1-77.5) with liver metastases of non-colorectal carcinomas- NKJM (the commonest types: breast carcinoma--32.4%, carcinoid--20.6%, renal carcinoma--13.3%, gynecological tumors--13.3%, gastrointestinal stromal tumor--4.4%, gastric carcinoma--4.4% ) during 2001-2008. The mean time after primary surgery for carcinoma was 3.9 years (0-8.5 let). The surgical procedures included the following: radiofrequency ablation (RFA)--50 patients (73.5%), resections in 26.5%. Preoperative chemotherapeutical "downstaging" or portal vein embolization on the tumor side, in order to improve the NKJM resecability, was performed in 10 subjects (14.7%). Resecable or RFA--manageable extrahepatic metastases were removed using one- or more- step procedures in 25 subjects (36.7%). The total number of liver metastases within the whole study group ranged from 1 (28x) to 8 (1x) metastases. Postoperative adjuvant chemotherapy, combined with biological treatment in some patients, was administered to a total of 33 patients (48.5%). RESULTS: One year after the procedure and RFA, a total of 88.6% of patients were surviving, at 3 years 72.5 % and at 5 years 36.9% of the subjects. Considering four commonest tumors (breast carcinoma, carcinoid, gynecological carcinomas and renal carcinoma), the best 5-year survival rates were recorded in patients with carcinoid metastases (100%), 33.8% of patients with breast metastases were surviving at 5 years, 44.4% of patients with renal carcinoma metastases were surviving at 3 years and 72.9% of patients with gynecological tumors were surviving at 2 years. There were no statistically significant differences in long-term survival rates between RFA and resections. Patients with extrahepatic metastases had worse prognosis (p < 0.01). CONCLUSION: Liver resection and RFA have their definite place in multimodal treatment strategy in the management of non- colorectal carcinoma liver metastases (NKJM). Indication for surgery must be made on strictly individual basis, in particular in patients with NKJM, in order to achieve quality long-term survival in these patients.

Cytokines and liver regeneration after partial portal vein ligation in porcine experimental model.

THE AIM OF STUDY: The limits of liver surgery are restricted today by the functional reserves of remnant parenchyma. The aim of this article was to acquaint the general surgical and medical public with the results of experimental liver regeneration stimulated by cytokines and thus to enhance their effort to carry on with implementing the research results in clinical practice. METHODS: Authors present their experimental model of liver regeneration after ligation of portal branches for caudate and right lateral, and right medial liver lobes. The regeneration was induced by application of TNF-alpha and IL-6 into the non-occluded portal branches, and compared with the results of other experimental teams. RESULTS AND CONCLUSION: The absolute volume of hypertrophic lobes increases after application of TNF-alpha more rapidly, whereas in the control group, practically no changes were recorded in hypertrophic liver lobes volumes in first three days. The achieved acceleration of growth of hypertrophic liver lobes after application of TNF-alpha and IL-6 confirmed the key role of studied pleiotropic cytokines in the priming of liver parenchyma regeneration after portal vein ligation (Fig. 3, Ref. 26).