[Show abstract][Hide abstract] ABSTRACT: All autonomic hepatic nerves are transected following liver transplantation. Recent studies have shown the relationship between an inhibition of autonomic nerves and the accumulation of hepatic progenitor cells (HPC). This study aims to elucidate the influence of hepatic denervation on the accumulation of HPC in the process of liver regeneration.
Male Sprague-Dawley rats underwent hepatic denervation. Immediately after either denervation (DN group, n=30) or a sham operation (control group, n=30), a two-thirds hepatectomy was performed, and these were sacrificed chronologically. An immunohistochemical analysis of HPC was performed with a mouse monoclonal OV6 type antibody.
The liver per body weight ratio gradually increased in both groups. On postoperative day (POD) 7, the DN group showed a significantly higher ratio. The HPC expression gradually increased in both groups. The maximal HPC number was observed on POD 7 in the DN group and on POD 3 in the control group. Although there was no significant difference in the HPC numbers between the DN and control group until POD 3, the number of HPC were significantly higher in livers of the denervated rats than in those of the sham operated rats between POD 5 and 14.
The hepatic autonomic nerves were thus suggested to play an important role in the accumulation of HPC during liver regeneration in rats.
[Show abstract][Hide abstract] ABSTRACT: Although hepatocyte transplantation holds great promise, most of the transplanted hepatocytes fail to proliferate in the liver without any manipulation of the host. Previous studies have shown that the replacement of the host liver cells with transplanted hepatocytes, called "liver repopulation", requires a combination of proliferative stimuli to the transplanted hepatocytes and suppression of the host hepatocytes. This study explored whether liver repopulation could be achieved by hepatocyte transplantation in a chemically and surgically induced-liver failure model in the rat.
Dipeptidyl peptidase IV-positive (DPPIV +) Fisher rats were used as donor and syngeneic DPPIV-deficient (DPPIV-) rats served as recipient. The recipient rats were treated with carbon tetrachloride (CCl4) for 4 weeks followed by a 68% partial hepatectomy (PH) and transplantation of the hepatocytes (HT). Five groups were established based on the influence of specific factors including CCl4, PH, and HT. The liver regeneration rates were evaluated by the liver weight/body weight (LW/BW) ratio. The liver repopulation rates were determined by the formula; (DPPIV+ cell counts/all cell counts) ×100%.
The liver regeneration rates were 3.5 and 2.6 in the rats with CCl4+PH, and PH alone, respectively (P<0.01). In the rats with CCl4+PH, DPPIV positive cell clusters appeared in the host liver parenchyma 7 days after HT (day 7), exhibiting continuous proliferation up to day 28 (The liver repopulation rates were 1.1% and 13.4%, respectively, p<0.05).
Liver repopulation by hepatocyte transplantation was therefore found to be possible in partially hepatectomized rats under the continuous exposure to regulated doses of CCl4.
Annals of transplantation: quarterly of the Polish Transplantation Society 12/2010; 15(4):49-55. · 1.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Many techniques have been described for the surgical repair of lumbar hernias, including primary repair, local tissue flaps, and conventional mesh repair. All these open techniques require a large incision plus extensive dissection to expose the hernia ring. This report presents a case of a recurrent lumbar hernia, which was successfully repaired using a laparoscopic approach.
A 75-year-old female presented with a symptomatic right lumbar hernia, 1-year after an iliac bone harvest for knee surgery. Under general anesthesia, the patient was placed in a lateral decubitus position. A 3 trocar technique was used to do adhesiolysis of the surrounding tissues, to provide an ample working space to identify the hernia. A composix dual mesh (bard) was tailored so that it would overlap the defect with intermittent fixation by a spiral tacker (protac). No hernia recurrence occurred over 2 years after surgery.
The laparoscopic approach has significant advantages for the repair a lumbar hernia: it enables the exact localization of the anatomic defect, and the mesh can be placed deep into the defect, thus allowing the intraabdominal pressure to hold it in position.
[Show abstract][Hide abstract] ABSTRACT: To elucidate the metabolism and the effect of the cyclosporin A (CyA) as a representative immunosuppressive drug used in transplantation in a partially hepatectomized rat model.
CyA was administered to rats that underwent a 70% hepatectomy. These rats were randomly assigned into three groups according to the dose of CyA administration as follows; (group 1) water, (group 2) 5 mg/kg CyA, (group 3) 10 mg/kg CyA. On postoperative days-1, 3, 7 and 14, the rats were killed to analyze the serum concentration of CyA, the liver regeneration ratio, biochemical or histological markers, and mRNA expression using reverse transcriptase-polymerase chain reaction method to determine albumin and cytochrome p450 expression.
The serum concentration of CyA in group 3 was significantly higher than group 2 during liver regeneration. CyA enhanced the liver regeneration in a dose dependent manner. The mRNA expression associated with CyA metabolism was significantly decreased on day 14, while preserving the albumin producing activity.
These data indicate that the p-450 activity required to metabolize the CyA may be reduced during regeneration of the remnant liver after a hepatectomy, which may, therefore, be linked to difficulty in controlling the optimal dose of CyA during early period of LDLT.
World Journal of Gastroenterology 12/2008; 14(41):6355-9. · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aim: Hepatocellular carcinoma (HCC) arising from the end stages of liver cirrhosis is a fair indication for liver transplantation (LT). To pathologically investigate the multicentric occurrence of relatively early staged HCC in cirrhosis, we studied whole explanted livers.Methods: Fourteen explanted livers from patients undergoing living donor LT (LDLT) were examined. The stage of the HCCs was judged to be within the Milan criteria (M-C; a single HCC less than 5 cm or three HCCs less than 3 cm). Histological examination was performed using serially sectioned specimens 5–7 mm in width. Characterization of preoperatively detectable and undetectable lesions was also performed.Results: In nine patients (64.3%), a total of 34 nodules were found after whole liver histological examination (WLHE). In five patients (31%), the results exceeded the M-C. The characteristics of undetectable HCCs included a minute (median size 6 mm), well-differentiated appearance (80%), with indistinct margins (85.3%) and without vascular invasion (94%). There was no recurrence in any patients at the time of follow up (median follow-up period, 30.1 months).Conclusion: A multicentric occurrence of HCCs was demonstrated in cirrhotic livers with HCCs within the M-C. Undetectable HCCs in cirrhotic livers may have no impact on recurrence after LT.
[Show abstract][Hide abstract] ABSTRACT: E-cadherin (E-cad) is a type of adhesion molecule, and recent studies have demonstrated a correlation between its expression in tumor lesions and the recurrence of HCC. Serum levels of soluble E-cad are significantly elevated in patients with several types of cancer. The authors evaluated the significance of the serum level of soluble E-cad as a predictor of early recurrences (intrahepatic or extrahepatic metastasis) of HCC after a curative resection.
The concentrations of soluble E-cad in the serum of 25 HCC patients before surgery and 12 healthy subjects were measured using a sandwich enzyme-linked immunosorbent assay. The hepatic expression of E-cad was examined by immunohistochemical staining.
The median serum soluble E-cad levels were significantly elevated in HCC patients before surgery in comparison to those in healthy subjects (10,759 ng/mL vs. 5,798 ng/mL, p < 0.05). The patients in the high serum soluble E-cad group experienced a higher incidence of early recurrence (p < 0.05). The levels of expression of E-cad in HCC lesions were not related to the serum levels of soluble E-cadherin.
The study demonstrated that serum soluble E-cad levels were elevated in patients with HCC, and high serum soluble E-cadherin (> or = 8,000 ng/ml) was associated with early recurrence or extrahepatic metastasis. Serum soluble E-cad may therefore be a potential prognostic marker for HCC.