Ex vivo hepatic venography for hepatocellular carcinoma in livers explanted for liver transplantation

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is supposed to have a venous drainage system to a portal vein, which makes intrahepatic metastasis possible. However, the mechanism of extrahepatic recurrence, including the possibility of a direct route to the systemic circulation from the HCC nodules, remains unclear. Therefore, we performed retrograde hepatic venography for HCC in livers that had been explanted for liver transplantation in order to explore the possible direct connection between the hepatic vein and HCC nodules.</p> <p>Methods</p> <p>Of 105 living-donor liver transplantations (LDLT) performed up to July, 2009 at the Department of Surgery, Nagasaki University Hospital, dynamic hepatic venography was performed with contrast media under fluoroscopy for the most recent 13 cases with HCC. The presence of a tumor stain for each HCC case was evaluated and compared with the histological findings of HCC.</p> <p>Results</p> <p>Hepatic venography revealed a tumor stain in 2 of 13 cases (15%). Neither showed any microscopic tumor invasion of HCC into the hepatic vein. In the other 11 cases, there were 4 microscopic portal venous invasions and 2 microscopic hepatic venous invasions. No patients have shown HCC recurrence in follow-up (median period, 13 months).</p> <p>Conclusion</p> <p>Using <it>ex vivo </it>hepatic venography, a direct connection to the hepatic vein from HCC in whole liver was revealed in 2 cases without demonstrated histopathological invasion to hepatic vein for the first time in the literature. The finding suggests that there is direct spillage of HCC cells into the systemic circulation via hepatic vein.</p

Perioperative synbiotic treatment to prevent infectious complications in patients after elective living donor liver transplantation. A prospective randomized study.

BACKGROUND: Although the effect of synbiotic therapy using prebiotics and probiotics has been reported in hepatobiliary surgery, there are no reports of the effect on elective living-donor liver transplantation (LDLT). METHODS: Fifty adult patients undergoing LDLT between September 2005 and June 2009 were randomized into a group receiving 2 days of preoperative and 2 weeks of postoperative synbiotic therapy (Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides [the BLO group]) and a group without synbiotic therapy (the control group). Postoperative infectious complications were recorded as well as fecal microflora before and after LDLT in each group. RESULTS: Only 1 systemic infection occurred in the BLO group (4%), whereas the control group showed 6 infectious complications (24%), with 3 cases of sepsis and 3 urinary tract infections with Enterococcus spp (P = .033 vs BLO group). No other type of complication showed any difference between the groups. CONCLUSIONS: Infectious complications after elective LDLT significantly decreased with the perioperative administration of synbiotic therapy

Rapid production of engineered human primary hepatocyte/fibroblast sheets

This data article contains data related to the research article entitled "Vascularized subcutaneous human liver tissue from engineered hepatocyte/fibroblast sheets in mice," published in Biomaterials [1]. Engineered hepatocyte/fibroblast sheets (EHFSs) are used for construction of vascularized subcutaneous liver tissue without a pre-transplant vascularization procedures. Here, we described a rapid production technique of EHFSs by controlling fibroblast density and coating fetal bovine serum (FBS) onto temperature-responsive culture dishes (TRCDs). The human fibroblast monolayer formed on FBS-coated TRCDs within 1h when seeded at a high density (at least 1.56×105cells/cm2). The most rapid EHFS production was achieved soon after the adhesion of human primary hepatocytes onto the fibroblast layer

Transition of Serum Alkaline Phosphatase Isoenzymes during Liver Regeneration in Humans

Background/Aims: Serum alkaline phosphatase (ALP) levels tend to increase after hepatectomy, however, no previous examinations have yet focused on the relationship between liver regeneration and the individual ALP isoenzymes levels. Methodology: Forty living liver transplantation donors who underwent hemi-hepatectomy were herein investigated. We evaluated the serum ALP levels and ALP isoenzyme levels preoperatively and postoperatively. The liver regeneration rate (LRR) was calculated using volumetry. According to the LRR, we divided the donors into two groups, consisting of a high regeneration group (HG) and a low regeneration group (LG). Results: The total serum ALP levels increased gradually after hepatectomy and peaked on postoperative days (POD) 14. ALP-1 was not detected in any donor preoperatively; however it was detected after hepatectomy, peaking on POD 7. The serum ALP-2 level increased after hepatectomy, reaching a peak level on POD 14. The ALP-2 levels gradually increased after hepatectomy and reached peak levels on POD 14 in both groups. However, the ALP-2 level on POD 14 was significantly higher in HG than LG. Conclusions: The serum ALP- 2 levels after POD 14 might therefore be a useful indicator of favorable liver regeneration following hepatectomy, especially in patients who have a normal liver function

Transition of serum alkaline phosphatase isoenzymes during liver regeneration in humans

Background/Aims: Serum alkaline phosphatase (ALP) levels tend to increase after hepatectomy. However, no previous examinations have yet focused on the relationship between liver regeneration and the individual ALP isoenzymes level. Methodology: Forty living liver transplantation donors who underwent hemi-hepatectomy were herein investigated. We evaluated the serum ALP levels and ALP isoenzyme levels preoperatively and postoperatively. The liver regeneration rate (LRR) was calculated using volumetry. According to the LRR, we divided the donors into two groups, consisting of a high regeneration group (HG) and a low regeneration group (LG). Results: The total serum ALP levels increased gradually after hepatectomy and peaked on postoperative day (POD) 14. ALP-1 was not detected in any donor preoperatively. However, it was detected after hepatectomy, peaking on POD 7. The serum ALP-2 level increased after hepatectomy, reaching a peak level on POD 14. The ALP-2 levels gradually increased after hepatectomy and reached peak levels on POD 14 in both groups. However, the ALP-2 level on POD 14 was significantly higher in HG than LG. Conclusions: The serum ALP-2 levels after POD 14 might therefore be a useful indicator of favorable liver regeneration following hepatectomy, especially in patients who have a normal liver function

Rat hepatocyte spheroids formed on temperature-responsive PIPAAm polymer-grafted surface maintain long-term differentiated hepatocyte function

Background.Although the development of a practicable culture method to maintain long-term hepatocyte function is highly desirable, hepatocytes lose their liver-specific functions rapidly on regular collagen-coated dishes. In this study, we evaluated the efficacy of a special cell culture dish coated with the temperature-responsive polymer poly(N-isopropylacrylamide) (PIPAAm), and observed the morphological and functional changes of hepatocytes on changing the amount of polymer.Methods.Culture plates with varying amounts of PIPAAm polymer (1.5～3.5 times that in the commercially available temperatureresponsive polymer-containing dish (UpCellR, CellSeed, Tokyo, Japan)) were prepared. All dishes were enhanced by adding a layer of rat tail collagen I at a dose of 600 μg/dish for 3 hours. Hepatocytes isolated from Sprague-Dawley rats were cultured in these static culture systems. Morphologic changes and liver-specific functions were evaluated.Results.On day 7 of culture, spheroid formation of hepatocytes was observed in the high-polymer group, with the presence of glycogen and albumin in the spheroid. In the high-polymer group, the rate of albumin production was significantly higher than in the low-polymer group until day 14 of culture (P<0.001).Conclusion.The spheroid formation of hepatocytes cultured in the presence of a high level of PIPAAm showed the long-term maintenance of liver-specific functions in vitro

Is preservation of middle hepatic vein tributaries during right hemi-hepatectomy beneficial for live donor liver transplantation?

Background/Aims: When right hemi-hepatectomy without middle hepatic vein (MHV) is performed in a living donor (LD), MHV tributaries such as V5 and V8 may be preserved during parenchymal transection to preserve liver function and reduce the damage of the graft. However, no study has so far investigated whether this preservation of MHV tributaries during parenchymal transection has impact on live donor operation or graft function. Methodology: Of 52 hepatectomies for right lobe LD, MHV tributaries were preserved during hepatic parenchymal transection in 11 cases, while, in the remaining 41 cases MHV tributaries were sacrificed when those were encountered during hepatic parenchymal transection. Results: There was no significant difference in blood loss, operative time, zenith liver enzyme level in a donor and rate of graft failure in a recipient. Conclusions: It was demonstrated that there was no significant effect of outflow preservation from MHV tributaries on LD hepatectomy for right lobe donation and subsequent liver transplantation

Are there any similarities in the hepatic vascular anatomy among blood relatives?

Background/Aims: The existence of similarities in the hepatic vascular anatomy among blood relatives (BR) have never been studied before. Since in living donor liver transplantation (LDLT), the donor may be a BR, an opportunity is available to assess whether there are similarities in the hepatic vascular anatomy among BR. Methodology: We conducted an analysis of 61 LDLT during the period from January 2004 to August 2008. Based on preoperative multi-detector computed tomography data, the hepatic arteries (HA) were classified into 4 groups, the portal vein (PV) was classified into 2 groups and the right hepatic vein (RHV) was classified into 2 groups. The data of each group were then compared between BR (n=47) and NBR (n=14). Results: With regard to the HA anatomy, 30 cases (68%) of the BR donor matched that of the recipient and 9 cases (69%) in the NBR donor. The PV anatomy was matched in 41 cases (87%) of BR donor and 11 cases (79%) in the NBR donor. The anatomy of the RHV was matched in 25 cases (53%) in the BR donor and 9 cases (64%) in NBR donor. There was no significant difference in all contexts. Conclusions: No similarities were therefore observed in the hepatic vascular anatomy among BR

Expression of alpha smooth muscle actin in living donor liver transplant recipients

Recently, there have been reports from liver biopsies that showed the progression of liver fibrosis in liver transplant patients after the cessation of immunosuppression. Herein, we focused on activated hepatic stellate cells expressing alpha smooth muscle actin (α-SMA) to understand the correlation between immunosuppressant medication and liver fibrosis. The study enrolled two pediatric patients who underwent living donor liver transplantation and ceased immunosuppressant therapy. The number of α-SMA-positive cells in the specimens obtained by liver biopsy from these two patients showed a three-fold increase compared with the number from four transplanted pediatric patients who were continuing immunosuppressant therapy. In addition, the α-SMA-positive area evaluated using the Win- RooF image processing software program continued to increase over time in three adult transplanted patients with liver fibrosis, and the α-SMA-positive area was increasing even during the pre-fibrotic stage in these adult cases, according to a retrospective review. Therefore, α-SMA could be a useful marker for the detection of early stage fibrosis