Long‐term impact and clinical significance of living donor liver transplantation with respect to donor liver restoration and spleen size: A prospective study

This study aimed to evaluate postoperative long‐term liver restoration and splenic enlargement and their clinical significance in living donor liver transplantation. One hundred and sixteen donors who had donated livers more than 5 years previously accepted the invitation to participate in this study. The liver restoration rate and the splenic enlargement rate were calculated as the rate with respect to the original volume. The mean liver restoration rate was 0.99 ± 0.12 and older age was associated with a higher incidence for liver restoration rate <0.95 (P = .005), whereas type of donor operation was not. The donors with liver restoration rate <0.95 showed lower serum albumin levels than those with liver restoration rate ≥0.95. The mean splenic enlargement rate was 1.10 ± 0.16. Right lobe donors demonstrated higher splenic enlargement rate (1.14 ± 0.18) than left lobe/lateral segment donors (1.06 ± 0.13). In the donors with splenic enlargement rate ≥1.10, platelet count was not fully restored to the preoperative level. In conclusion, older age increases the risk for incomplete postoperative liver restoration, which may be associated with a decrease in albumin more than 5 years after donation. Right lobe donation poses a risk of splenic enlargement, which is associated with incomplete restoration of platelet count.     

High risk of lung metastasis after resection of hepatocellular carcinoma more than 7 cm in diameter

Purpose

The relationship between the tumor size and organs of recurrence was analyzed to identify a high-risk group for the extrahepatic recurrence of hepatocellular carcinoma (HCC) after resection.

Methods

A total of 544 patients with HCC underwent primary surgical resection for HCC between 2001 and 2010. Of these, 293 patients had a solitary tumor but no macroscopic vascular invasion. The prognostic factors for the overall survival and relapse-free survival were analyzed among these 293 patients. The recurrent organs and frequency of recurrence were also examined.

Results

The analysis of the 293 patients showed that both the overall and relapse-free survival rates of the patients with a large tumor (>7 cm in diameter) were significantly worse than those of the patients with a tumor <7 cm. The incidence of lung metastasis was remarkably high in the group of patients with tumors more than 7 cm (24.0 %), in comparison to those with tumors <7 cm. A multivariate analysis revealed that the tumor size was the only independent risk factor for lung metastasis.

Conclusions

The patients with large HCC tumors more than 7 cm in diameter were at high-risk for a poor prognosis due to a high percentage of lung metastasis, even if there was no macroscopic vascular invasion.     

Beta-catenin expression in hepatocellular carcinoma: a possible participation of beta-catenin in the dedifferentiation process

BACKGROUND: beta-Catenin is known as a multifunctional protein acting as a regulator of the cadherin-mediated cell-cell adhesion system and in the Wingless/Wnt signal transduction pathway. Recent studies reported mutation of the beta-catenin gene in some tissues of hepatocellular carcinoma (HCC). METHODS: 'Nodule-in-nodule' appearance is a feature of well-differentiated HCC containing a distinct nodule of less-differentiated cancer tissue inside, and it is presumed to be a morphological expression of the dedifferentiation process. The present study immunohistochemically investigated the beta-catenin expression according to the dedifferentiation process of HCC, that is, in small well-differentiated HCC with indistinct margins, HCC with a 'nodule-in-nodule' appearance, moderately differentiated HCC, which does not have a 'nodule-in-nodule' appearance, and sarcomatous HCC. RESULTS: The expression of beta-catenin was observed in approximately 70% of small well-differentiated HCC with indistinct margins. In HCC with a 'nodule-in-nodule' appearance, membranous expression of beta-catenin was higher in the well-differentiated cancer tissues than in the less-differentiated cancer tissues (P < 0.01), cytoplasmic expression was higher in the less-differentiated cancer tissues (P < 0.01), and nuclear expression was higher in the less-differentiated cancer tissues (P < 0.001). In moderately differentiated HCC, tumors with membranous expression of beta-catenin had more frequent intrahepatic metastasis than those without having the expression (P < 0.001). CONCLUSIONS: Accumulation of beta-catenin was already present in the early stage of HCC, and in less-differentiated cancer tissue the membranous expression of beta-catenin could be related to intrahepatic metastasis.     

High concentration simvastatin induces apoptosis in fibroblast-like synoviocytes from patients with rheumatoid arthritis

OBJECTIVE: We previously reported that 10 mg/day of simvastatin significantly reduced clinical scores of rheumatoid arthritis (RA) in patients with active RA with hypercholesterolemia. We have also reported that a certain pharmacological concentration of simvastatin, i.e., 0.05-0.1 microM, inhibits the production of interleukin 6 (IL-6) and IL-8 and the cell proliferation induced by tumor necrosis factor-alpha (TNF-alpha) in fibroblast-like synoviocytes (FLS) derived from patients with RA in vitro. We investigated other effects of simvastatin on FLS from the standpoint of cell viability and apoptosis. METHODS: RA FLS were cultured with or without 0.05-50 microM simvastatin for 48 h. Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was measured by flow cytometric analysis using propidium iodide and annexin-V. Caspase-3 and -9 activities were analyzed by colorimetric assays. RESULTS: High concentrations of simvastatin, i.e., 1.0-50 microM, reduced cell viability and induced prominent apoptosis in FLS in a dose-dependent manner. The apoptosis induced by simvastatin was caspase-3- and caspase-9-dependent. These effects were completely reversed in the presence of mevalonic acid or geranylgeranyl-pyrophosphate, but not in the presence of farnesyl-pyrophosphate. Further, a geranylgeranyl transferase inhibitor and a RhoA kinase inhibitor mimicked the effect of simvastatin. CONCLUSION: These data, together with our previous report, suggest that low (pharmacological range) and high concentrations of simvastatin affect FLS differently: (1) at a low concentration, it inhibits IL-6 and IL-8 production and the cell proliferation of FLS induced by TNF-alpha (2) at high concentrations, it induces apoptosis in FLS. Understanding this dose-dependent biphasic effect of simvastatin may prove important for its clinical applications in the treatment of RA.     

Expression of N-acetylglucosaminyltransferase V in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder

Background

N-Acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the β1-6 branching of N-acetylglucosamine on asparagine-linked oligosaccharides of cellular proteins, enhances the malignant behaviors of carcinoma cells in experimental models. The aim of this study was to determine clinical significance of GnT-V expression in human pT₂ gallbladder carcinoma with simple in vitro experiments.

Methods

Ninety patients with pT₂ gallbladder carcinoma were included for this study. The in vitro and in vivo biological effects of GnT-V were investigated using gallbladder carcinoma cells with variable GnT-V expression levels induced by a small interfering RNA.

Results

Of the 90 cases, 57 showed positive staining and the remaining 33 demonstrated negative staining, the subcellular localization in the 57 cases was classified into the granular-type in 31 cases and the diffuse-type in 26 cases. In 76 cases with curative resection, postsurgical survival was significantly poorer in those showing positive staining than in those showing negative staining (P = 0.028). In all of the 76 cases, postsurgical recurrence was significantly more frequent in those showing diffuse-type localization than in those showing negative staining. Experimental analyses demonstrated that the down-regulation of GnT-V expression in gallbladder carcinoma cells induced suppression of cell growth in vitro. The expression levels of GnT-V in the cells were highly correlated with the rapid in vivo growth coupled with the enhanced angiogenesis, and the tendency to form liver metastasis.

Conclusions

GnT-V expression in the subserosal layer of pT₂ gallbladder carcinoma is correlated with the aggressiveness of the disease.     

Role of male pelvic floor muscles and anterior fibromuscular stroma in males on α1‐blocker treatment: A magnetic resonance imaging study

Dynamic motion of the pelvic floor muscles during voiding was analyzed using real‐time magnetic resonance imaging. To evaluate the contraction of the pelvic floor muscles, striated urethral sphincter distance, levator ani muscle thickness and anterior fibromuscular stroma distance were measured. The percent contraction of the striated urethral sphincter from before voiding to just before initiation of voiding was 14% in the normal group and 5% in the voiding dysfunction group. The percent contraction of the anterior fibromuscular stroma from before voiding to just before initiation of voiding was 11% in the normal group and 1% in the voiding dysfunction group; the percent contraction of the muscles was significantly greater in the normal group (P < 0.05). Striated urethral sphincter and anterior fibromuscular stroma contraction at initiation of voiding open the bladder neck and urethra. This plays an important role in the smooth initiation of voiding.