Jacques Van Huysse

The value of laparoscopic liver surgery for solid benign hepatic tumors

BackgroundLaparoscopic liver resection (LLR) has gained wide acceptance for various liver resection procedures, mainly for benign diseases. However, only small series have been reported from a few selected centers.MethodsBetween January 2001 and January 2006, a total of 629 liver resections were performed at our institution. The indication was solid benign liver tumor in 56 (8.9%) patients. LLR was performed in 20 (35.7%) cases. Data from the LLR group were compared with those from a consecutive control group undergoing open liver surgery (OS) for similar indications in a matched-pair analysis during the same period. The pairs were matched as closely as possible for age, gender, American Society of Anesthesiologists (ASA) score, indication for resection, and type and location of the lesions. The endpoint was to investigate overall morbidity and outcome.ResultsAll patients but one are alive and well after a mean follow-up of 35 months (range 10–60 months). Conversion laparotomy was required in two out of 20 (10%) cases for uncontrolled bleeding (one requiring temporary hemodialysis). LLR was characterized by faster time to first oral intake and shorter hospital stay compared to OS (p = 0.001 and 0.008, respectively). Incisional hernias (25%) were only recorded in the OS (p = 0.047 vs. LLR). Overall morbidity was 45% in OS versus 20% in LLR (p = 0.3).ConclusionsLLR significantly reduced time to oral intake, hospital stay, and incisional hernias compared to OS. Bleeding is a major risk and should be carefully considered when resecting benign tumors. In the hands of expert surgeons, LLR may become the gold standard for the resection of benign liver tumors located in the anterior and lateral sectors and for minor hepatic resections.

An intravital microscopic study of the hepatic microcirculation in cirrhotic mice models: relationship between fibrosis and angiogenesis

This intravital fluorescence microscopy (IVFM) study validates cirrhotic mice models and describes the different intrahepatic alterations and the role of angiogenesis in the liver during genesis of cirrhosis. Cirrhosis was induced by subcutaneous injection of carbon tetrachloride (CCl4) and by common bile duct ligation (CBDL) in mice. Diameters of sinusoids, portal venules (PV), central venules (CV) and shunts were measured at different time points by IVFM. Thereafter, liver samples were taken for sirius red, CD31, Ki67, vascular endothelial growth factor (VEGF) and α‐smooth muscle actin (α‐SMA) evaluation by immunohistochemistry (IHC). In parallel with fibrogenesis, hepatic microcirculation was markedly disturbed in CCl4 and CBDL mice with a significant decrease in sinusoidal diameter compared to control mice. In CCl4 mice, CV were enlarged, with marked sinusoidal‐free spaces around CV. In contrast, PV were enlarged in CBDL mice and bile lakes were observed. In both mice models, intrahepatic shunts developed gradually after induction. During genesis of cirrhosis using CD31 IHC we observed a progressive increase in the number of blood vessels within the fibrotic septa area and a progressively increase in staining by Ki67, VEGF and α‐SMA of endothelial cells, hepatocytes and hepatic stellate cells respectively. In vivo study of the hepatic microcirculation demonstrated a totally disturbed intrahepatic architecture, with narrowing of sinusoids in both cirrhotic mice models. The diameters of CV and PV increased and large shunts, bypassing the sinusoids, were seen after both CCl4 and CBDL induction. Thus present study shows that there is angiogenesis in the liver during cirrhogenesis, and this is probably due partially to an increased production of VEGF.

Monoclonal antibody 14C5 targets integrin αvβ5

This study identifies and characterizes the antigen recognized by monoclonal antibody (mAb) 14C5. We compared the expression of antigen 14C5 with the expression of eight integrin subunits (α1, α2, α3, αv, β1, β2, β3, and β4) and three integrin heterodimers (αvβ3, αvβ5, and α5β1) by flow cytometry. Antigen 14C5 showed a similar expression to αvβ5 in eight different epithelial cancer cell lines (A549, A2058, C32, Capan-2, Colo16, HT-1080, HT-29, and SKBR-3). Specific binding of P1F6, an anti-αvβ5 specific antibody, was blocked by mAb 14C5. After transient expression of αvβ5 in 14C5-negative Colo16 cells, mAb 14C5 was able to bind a subpopulation of αvβ5-positive cells. We evaluated the tissue distribution of the 14C5 antigen in colon (n = 20) and lung (n = 16) cancer tissues. The colon carcinoma cells stained positive for 14C5 in 50% of tumors analyzed, whereas bronchoalveolar lung carcinoma and typical carcinoid were not positive for the antigen. More common types of non–small cell lung cancer, i.e., squamous (n = 5) and adenocarcinoma (n = 3), stained positive in 2 of 5 squamous carcinomas and in 1 of 3 investigated adenocarcinoma. Colon (95%) and lung (50%) carcinoma tissues showed extensive expression of antigen 14C5 in the stroma surrounding the tumor cells and on the membrane of the adjacent fibroblasts. We show for the first time that mAb 14C5 binds the vascular integrin αvβ5, suggesting that mAb 14C5 can be used as a screening agent to select colon and lung cancer patients that are eligible for anti-αvβ5–based therapies. [Mol Cancer Ther 2008;7(12):3771–9]

Alteration of N -glycome in diethylnitrosamine-induced hepatocellular carcinoma mice: a non-invasive monitoring tool for liver cancer

Background and aims: There is a demand for serum markers that can routinely assess the progression of liver cancer. DENA (diethylnitrosamine), a hepatocarcinogen, is commonly used in an experimental mouse model to induce liver cancer that closely mimics a subclass of human hepatocellular carcinoma (HCC). However, blood monitoring of the progression of HCC in mouse model has not yet been achieved. In this report, we studied glycomics during the development of mouse HCC induced by DENA.

Expression of placental growth factor in regenerating livers after partial hepatectomy in the rat.

Background/aims Placental growth factor (PlGF) is known for its role in pathological conditions to protect parenchymal cells of different organs from injury, whereas its presence in the liver and its potential importance in stimulating liver regeneration has never been described. This was investigated in this study using a rat model of partial hepatectomy (PH). Methods The rat model of 70, 80, and 90% PH was used. Liver samples were taken peroperatively, 1 h, 1, 2, 3, and 7 days after surgery. Liver regeneration was evaluated by liver weight/body weight ratio, liver regeneration rate (%), and proliferating cell marker Ki67. The expression of PlGF, vascular endothelial growth factor (VEGF), VEGF receptor 1 (Flt-1), VEGF receptor 2 (Flk-1), and hypoxia inducible factor-1&agr; mRNA was measured by quantitative real-time PCR and localized by immunohistochemistry. Results The mRNA expression of PlGF was upregulated immediately after PH. Compared with 70 and 80% PH groups, the 90% PH group had a significantly lower PlGF and hypoxia inducible factor-1&agr; mRNA expression, in parallel to a delayed liver weight/body weight ratio recovery. Only little differences were observed in VEGF, Flt-1, and Flk-1 mRNA expression among the PH groups. Conclusion This study shows for the first time the PlGF upregulation in regenerating livers, which is related to hypoxia stimulation and liver growth. The swift PlGF upregulation immediately after PH may indicate an important role for the PlGF/Flt-1 pathway in the early stage of liver regeneration.

S1657 Absence of Placental Growth Factor Aggravates DSS-Induced Acute Colonic Injury

METHODS: Acute DSS colitis was induced in PlGF knock-out (-/-) and wild-type (WT) mice. Disease activity was calculated during the course of the experiment. Mice were sacrificed at several timepoints. Colonic injury was evaluated by colon length, intestinal epithelial apoptosis (TUNEL assay) and histological score. PlGF and VEGF were measured in distal colonic lysates by ELISA. Mucosal vascularization was quantified by computerized morphometric analysis of CD31 stained distal colonic sections. Intestinal hypoxia was visualized by pimonidazole staining and semi-quantitatively analysed by western blot for hypoxia inducible factor alpha (HIF-1α).