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Upregulation of heme oxygenase-1 (HO-1) has been proposed as an adaptive mechanism protecting against ischemia/reperfusion (I/R) injury. We investigated HO-1 expression in 38 human liver transplants and correlated this with I/R injury and graft function. Before transplantation, median HO-1 mRNA levels were 3.4-fold higher (range: 0.7-9.3) in donors than in normal controls. Based on the median value, livers were divided into two groups: low and high HO-1 expression. These groups had similar donor characteristics, donor serum transaminases, cold ischemia time, HSP-70 expression and the distribution of HO-1 promoter polymorphism. After reperfusion, HO-1 expression increased significantly further in the initial low HO-1 expression group, but not in the high HO-1 group. Postoperatively, serum transaminases were significantly lower and the bile salt secretion was higher in the initial low HO-1 group, compared to the high expression group. Immunofluorescence staining identified Kupffer cells as the main localization of HO-1.In conclusion, human livers with initial low HO-1 expression (<3.4 times controls) are able to induce HO-1 further during reperfusion and are associated with less injury and better function than initial high HO-1 expression (>3.4 times controls). These data suggest that an increase in HO-1 during transplantation is more protective than high HO-1 expression before transplantation.Key words: Cytoprotection, heme-oxygenase-1, ischemia/reperfusion injury, liver transplantation Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; AUC, area under the curve; CO, carbon monoxide; GGT, gamma glutamyltransferase; HO-1, heme oxygenase-1; HSP-70, heat shock protein-70; I/R injury, ischemia/reperfusion injury; mRNA, messenger ribonucleicacids; OLT, orthotopic liver transplantation; ROS, reactive oxygen species.

Liver transplantation with preservation of the inferior vena cava. A comparison of conventional and piggyback techniques in adults Conventional orthotopic liver transplantation (CON-OLT) with resection of the native liver of the recipient together with the retrohepatic inferior vena cava (IVC) and interposition of the donor IVC attached to the new graft, has been the most common surgical approach in liver transplantation Miyamoto S, Polak WG, Geuken E, Peeters PMJG, de Jong KP, Porte RJ, van den Berg AP, Hendriks HG, Slooff MJH. Liver transplantation with preservation of the inferior vena cava. A comparison of conventional and piggyback techniques in adults.Abstract: The aim of this study is to analyse a single centre's experience with two techniques of liver transplantation (OLT), conventional (CON-OLT) and piggyback (PB-ES), and to compare outcome in terms of survival, morbidity, mortality and post-operative liver function as well as operative characteristics. A consecutive series (1994)(1995)(1996)(1997)(1998)(1999)(2000) of 167 adult primary OLT were analysed. Ninety-six patients had CON-OLT and 71 patients had PB-ES. In PB-ES group two revascularization protocols were used. In the first protocol reperfusion of the graft was performed first via the portal vein followed by the arterial anastomosis (PB-seq). In the second protocol the graft was reperfused simultaneously via portal vein and hepatic artery (PB-sim). One-, 3-and 5-yr patient survival in the CON-OLT and PB-ES groups were 90, 83 and 80%, and 83, 78 and 78%, respectively (p ¼ ns). Graft survival at the same time points was 81, 73 and 69%, and 78, 69 and 65%, respectively (p ¼ ns). Apart from the higher number of patients with cholangitis and sepsis in CON-OLT group, morbidity, retransplantation rate and post-operative liver and kidney function were not different between the two groups. The total operation time was not different between both groups (9.4 h in PB-ES vs. 10.0 h in CON-OLT), but in PB-ES group cold and warm ischaemia time (CIT and WIT), revascularization time (REVT), functional and anatomic anhepatic phases (FAHP and AAHP) were significantly shorter (8.9 h vs. 10.7 h, 54 min vs. 63 min, 82 min vs. 114 min, 118 min vs. 160 min and 87 min vs. 114 min, respectively, p < 0.05). RBC use in the PB-ES group was lower compared to the CON-OLT group (4.0 min vs. 10.0 units, p < 0.05). Except for WIT and REVT there were no differences in operative characteristics between PB-Sim and PB-Seq groups. The WIT was significantly longer in PB-Sim group compared with PB-Seq group (64 min vs. 50 min, p < 0.05); however REVT was significantly shorter in PB-Sim group (64 min vs. 97 min, p < 0.05). Results of this study show that both techniques are comparable in survival and morbidity; however PB-ES results in shorter AAHP, FAHP, REVT and WIT as well as less RBC use. In the PB-ES group there seems to be no adavantage for any of the revascularization protocols.

The adenosine triphosphate (ATP)-binding cassette (ABC)-transporters ABCG5 and ABCG8 have been shown to mediate hepatic and intestinal excretion of cholesterol. In various (genetically modified) murine models, a strong relationship was found between hepatic expression of ABCG5/ABCG8 and biliary cholesterol content. Our study aimed to relate levels of hepatic expression of ABCG5 and ABCG8 to biliary excretion of cholesterol in man. From 24 patients who had received a liver transplant, bile samples were collected daily after transplantation over a 2-week period to determine biliary composition. Expression of ABCG5, ABCG8, MDR3, and BSEP was assessed by real-time polymerase chain reaction (PCR) in liver biopsy specimens collected before and after transplantation. Levels of hepatic ABCG5, ABCG8, and MDR3 messenger RNA (mRNA) were strongly correlated. After transplantation, the biliary secretion rate of cholesterol continuously increased, coinciding with gradual increases in bile salt and phospholipid secretion. In contrast, hepatic levels of ABCG5 and ABCG8 mRNA remained unchanged. Surprisingly, no correlation was found between the hepatic expression of ABCG5 and ABCG8 and rates of biliary cholesterol secretion, normalized for biliary phospholipid secretion. As expected, the concentration of biliary phospholipids correlated well with MDR3 expression. In conclusion, the strong relationship between ABCG5 and ABCG8 gene expression is consistent with the coordinate regulation of both genes, and in line with heterodimerization of both proteins into a functional transporter. Hepatic ABCG5/ABCG8 expression, at least during the early phase after transplantation, is not directly related to biliary cholesterol secretion in humans. This finding suggests the existence of alternative pathways for the hepatobiliary transport of cholesterol that are not controlled by ABCG5/ABCG8. (HEPATOLOGY 2005;42:1166-1174

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Background: Endometrial sampling for the surveillance of women with Lynch syndrome is an invasive and painful procedure. The aim of this study was to evaluate the feasibility of a less invasive procedure of collecting vital cells by vaginal tampons. Methods: This was a prospective feasibility study of women scheduled to undergo annual gynecological surveillance, including endometrial sampling. We included consecutive asymptomatic women with Lynch syndrome or first-degree relatives and asked them to insert a vaginal tampon 2-4 h before attending their outpatient appointment. Feasibility was evaluated by the following metrics: patient acceptance, pain intensity of each procedure (assessed by visual analog scale; range 0-10), and the presence of vital cells obtained by tampon-based or endometrial sampling methods. Two pathologists independently evaluated all samples. Results: In total, 25 of 32 approached women completed the tampon-based procedure, with 23 of these subsequently undergoing invasive endometrial sampling. The median visual analog scale scores for tampon use and invasive endometrial sampling were 0 (range, 0-10) and 5.5 (range, 1-10) (p < 0.001). None of the tampon samples analyzed by cytology showed endometrial cells, but they did contain vital squamous cells and granulocytes. By contrast, 18 (78%) of the invasive endometrial samples contained enough endometrial tissue for analysis. No endometrial abnormalities were found by endometrial sampling. Conclusions: Tampon-based endometrial surveillance was a well-accepted and non-painful procedure, and although tampons contained vital cells, they did not provide endometrial cells. However, this study was limited to asymptomatic women with Lynch syndrome (no endometrial pathology), indicating that research is needed to evaluate whether the tampon method has any utility for endometrial surveillance in women with Lynch syndrome.

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