Alan Sutnar

Relevance of miR-21 and miR-143 expression in tissue samples of colorectal carcinoma and its liver metastases

MicroRNAs, which are endogenously expressed regulatory noncoding RNAs, have an altered expression in colorectal cancer. The aim of our study was to assess the relationship of miR-21 and miR-143 expression to the prognostic/clinicopathological features of colorectal carcinoma (CRC) and colorectal liver metastases (CLM). The estimation was performed in 46 paired (tumor and control) tissue samples of CRC. Further, we studied 30 tissue samples of CLM. MiR-21 and miR-143 expressions were quantified by using the quantitative reverse transcription polymerase chain reaction method. Relation of miR-21 and miR-143 expression to disease-free interval (DFI) (Wilcoxon; P = 0.0026 and P = 0.0191, respectively) was recorded. There was shorter DFI in patients with a higher expression of miR-21 and, surprisingly, also in patients with a higher expression of miR-143, which is a putative tumor suppressor. There was a higher expression of miR-21 and lower expression of miR-143 in CRC tissue in comparison with adjacent normal colon tissue (P < 0.0001; P < 0.0001, respectively). Similarly, we observed a higher expression of miR-21 and a lower expression of miR-143 in CLM in comparison with normal colon tissue (P < 0.0001; P < 0.0001, respectively). Our results support the hypothesis about oncogenic function of miR-21 and show its relation to DFI. The role of miR-143 in carcinogenesis seems to be more complex.

Prognostic importance of some clinical and therapeutic factors for the effect of portal vein embolization in patients with primarily inoperable colorectal liver metastases

Introduction Portal vein embolization (PVE) may increase the resectability of liver metastases. However, the problem of PVE is insufficient growth of the liver or tumor progression in some patients. The aim of this study was to evaluate the significance of commonly available clinical factors for the result of PVE. Material and methods Portal vein embolization was performed in 38 patients with colorectal liver metastases. Effects of age, gender, time between PVE and liver resection, oncological therapy after PVE, indocyanine green retention rate test, synchronous, metachronous and extrahepatic metastases, liver volume before and after PVE, increase of liver volume after PVE and the quality of liver parenchyma before PVE on the result of PVE were evaluated. Results Liver resection was performed in 23 (62.2%) patients within 1.3 ±0.4 months after PVE. Tumor progression occurred in 9 (23.7%) patients and 6 (15.8%) patients had insufficient liver hypertrophy. Significant clinical factors of PVE failure were number of liver metastases (cut-off – 4; odds ratio – 4.7; p < 0.03), liver volume after PVE (cut-off 1000 cm3; odds ratio – 5.1; p < 0.02), growth of liver volume after PVE (cut-off 150 cm3; odds ratio – 18.7; p < 0.002), oncological therapy administered concomitantly with PVE (p < 0.003). Conclusions Negative clinical factors of resectability of colorectal cancer liver metastases after PVE included more than four liver metastases, liver volume after PVE < 1000 cm3, growth of the contralateral lobe by less than 150 cm3 and concurrent oncological therapy.

Liver Parenchyma Regeneration in Connection with Extended Surgical Procedure - Experiment on Large Animal

Liver surgery underwent enormous evolution after development and introduction of new technical skills in surgical praxis. Nevertheless many patients with primary or secondary liver malignancies are not indicated to radical surgical therapy that could reach complete remission of malignant disease because the frontiers of liver surgery are limited today by the functional reserves of remnant parenchyma. The main argument to non surgical treatment is increased risk of acute liver failure after extended liver resection, where retained liver parenchyma is to small to sustain the liver functions (Abdalla, 2001). Portal vein embolization (PVE) can multiply the future liver remnant volume (FLRV) in spite of affection of only one of liver lobes by malignant diseases (Makuuchi, 1984, Makuuchi, 1990, Harada, 1997). This procedure was performed firstly in 1984 by Makuuchi (Abdalla, 2001, Makuuchi, 1984, Makuuchi, 1990). PVE of portal branch of with malignancy afflicted liver lobe initiates compensatory hypertrophy of contralateral non-occluded lobe. The occluded lobe underlies atrophy. The compensatory hypertrophy is supposed to be stimulated by increased flow of portal blood, that contains hepatotrophic substances (Kusaka, 2004, Azoulay, 2000). Liver resection after PVE is performed only in 63-96% of patients (Kokudo, 200, Stefano, 2005, Lagasse, 2000). The main reason for this resolution is unsuccessful hypertrophy of FLRV or progression of malignancy. Liver resection after PVE is performed only in 63-96% of patients (Azoulay, 200, Kokudo, 2001, Stefano, 2005). The main reason for this resolution are unsuccessful hypertrophy of FLRV or progression of malignancy.

P2-15-06: Breast Cancer Liver Metastases – Possibilities and Limits of Surgical Treatment.

Background Breast cancer liver metastases (BCLM) are often considered as a sign of a systemic disease with little hope of therapeutic success. The aim of study was to assess the possibilities and determine the limits of the surgical treatment of BCLM. Method : 646 patients were operated for malignant and benign lesions of the liver between 1999 and 2010. Liver surgery for BCLM was performed in 21 women of the average age of 48.5 years (33-71). The average time from the primary surgery for breast cancer till BCLM diagnosis was 4.7 years (2 months - 9 years). BCLM were solitary in 17 and in four cases multiple. Patient selection for liver surgery was based on sufficient future remnant liver volume, the absence of systemic non-resectable tumor dissemination and response to chemotherapy. The authors performed six right-sided hepatectomy, four segmentectomies, three left lobectomies, one metastasectomy, six radiofrequency ablations (RFA), one combined procedure -liver resection and RFA. Histological examination revealed ductal carcinoma in fourteen and lobular carcinoma in seven cases. All patients were treated with the curative adjuvant chemotherapy after surgery. The data were statistically evaluated by statistical software Statistica 9.0. Results : 30 - days mortality rate was 0%. One patient had a complicated hepatectomy with iatrogenic bile duct injury. According to statistical analysis the probability of patients survival twelve, resp. thirty months after surgery was 100, resp. 66.7% and the probability of the tumor relapse anywhere in the body was at the same time intervals 0, resp. 71. 5%. Conclusion : Liver surgery combined with the adjuvant chemotherapy are a therapeutic methods of choice for highly selected patients with metastases limited to the liver and objective response to neoadjuvant chemotherapy. The study was supported by the research projects IGA MZ NS 9727 and IGA MZ NS 102 40. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-06.